IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\n
IntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\n
Designed to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\n
After a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\n
Our innovative Book Series format brings you:
\n\n
\n\t
Topic Focused Publications - Each topic showcases high impact subject areas
\n\t
Renowned Editorial Expertise - Series Editors, Topic Editors, and a team of international Board Members that permanently support each Book Series
\n\t
Fast Publishing - quick turnaround which is unique for book publishing
\n\t
The benefit of ISSN and ISBN for increased citation and indexing possibilities
\n
\n\n\n\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\n
IntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
We invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\n
Note: Edited in October 2021
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The book provides a comprehensive revision of bioactive peptides obtained from both animal and plant food sources. Aspects related to their bioactivity, mechanism of action, and bioavailability are extensively described along the different chapters. Also, the chapters describe the impact of bioactive peptides on the physiological absorption, regulation and disease prevention. The book also covers the recent technological advances for the production of food peptides. 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She was working (1998 to 2002) at the Institute of Industrial Fermentations (CSIC), earning her Ph.D. in Pharmacy by the Complutense University of Madrid, Spain in 2002. She continue working as postdoctoral fellow at the CSIC until 2007 when she moved to USA for a postdoctoral work at the University of California, Berkeley. In 2010, she went back to Spain to work as postdoctoral researcher under different contracts. 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1. Introduction
Exclusive breast feeding involves feeding only breast milk without any added fluids or solids. It is highly recommended by the World Health Organization (WHO) for the first 6 months of life with supplemental breast feeding continuing for at least 2 years [1]. This is because optimal breastfeeding of infants has a direct impact on growth, development, and health in the neonatal period [2, 3]. Breastfeeding is known to have invaluable benefits both for the child and mother. For the mother, breast feeding causes weight reduction, provides stronger interaction with the infant as well as pleasure and pleasant emotion. It also provides a more practical approach to feeding in comparison to the use of a bottle prevents breast cancer and pregnancy and provides relief in breast pain while also being economical. For the infant, it promotes affectional bond with the mother while adequately supplying the nutritional and emotional needs [3]. In the developing world, low immunization rates, contaminated drinking water, and reduced immunity as a result of malnutrition make breast feeding crucial to reducing life threatening infections. A review of interventions in 42 developing countries estimated that exclusive breast feeding for 6 months, with partial breastfeeding continuing to 12 months, can prevent 1.3 million (13%) deaths each year in children under 5 years [3]. However exclusive breastfeeding is not without challenges.
2. Challenges with breastfeeding
The WHO’s recommendation for breastfeeding has been adopted by several countries all over the World and also in West Africa, but this has presented with several challenges, hence reducing the number of children who could potentially be breastfed. In the United States, for example, less than half of infants receive any breast milk at 6 months (49.4%), and approximately one-quarter are breast-fed up to 1 year (26.7%) [4]. Breast discomfort or pain, sore nipples, mastatitis, inverted nipples, presence of breast implants, difficulty getting baby to suck, poor weight gain and hypernatremia dehydration due to insufficient milk intake are rampant challenges encountered during breast feeding [3]. Lactation failure is also common among postpartum women, resulting in insufficient milk supply which is a major reason for early weaning. It has been claimed that at least 5% of women experience lactation failure (agalactias) whiles approximately 15% of women experience inadequate supply of their breast milk (hypogalactias) [5] at 3 weeks postpartum. The number of lactating women who have produce insufficient breast milk is on the rise [2]. There are a number of well-known causes of low breast milk supply that is primarily related to breast feeding management. These factors are difficult to control and require a good knowledge of breastfeeding practices. These factors include; schedule breastfeeding, skipping breastfeeding, supplementing the diet of the baby with infant formulas and poor latching of the baby on the breast. However, there are more complicated causes of low breast milk supply such as; insufficient mammary tissue (hypoplasia), medications (hormonal contraceptive pills), retained placenta, diseases (diabetes, jaundice), metabolic conditions (obesity), previous breast surgeries, cesarean section, thyroid and other hormonal disorders. Another cause is even environmental toxins such as pesticides. A study found that daughters of women who grew up in a pesticide contaminated environment had much higher incidence of insufficient mammary tissue than those living on the hill top of the same an area [6].
3. Solutions to breastfeeding challenges
To respond to the challenge of insufficient milk production (hypogalactia) or the absence of milk production (agalactia) milk banks are being created and the use of medication that induces, maintains or increases milk production are being used [2, 7].
Throughout history, donor breast milk banks have been the choice of some parents, and it is currently recommended as second choice if the mother’s own milk is not available. However, the risk of possible transmission of diseases including HIV, cytomegalovirus, and Creutzfeldt-Jakob disease has induced the need for pasteurization. There are major concerns however as to what extent pasteurized donor breast milk retains the biological properties of mother’s milk. Evidence on donor milk quality is limited [3] and operational human milk banks are not able to meet demands for especially the most vulnerable neonates [8].
3.1 Synthetic galactagogues
Orthodox drugs that are widely used as galactagogues are chlorpromazine, sulpiride, metoclopramide and domperidone [2] but there are reservations as to their efficacy and their association with very high incidences of unpleasant side effects including extra-pyramidal effects in both mother and infant. There is therefore a need to keep searching for more acceptable, safe and efficacious galactagogues [2, 9]. In the United States, Canada and Europe, metoclopramide and domperidone are widely prescribed [10].
Metoclopramide though prescribed off-label as a lactation aid has one troublesome side-effect of inducing depression. Extrapyramidal symptoms also occur in about 1 in 500 patients at even usual adult doses resulting in involuntary movements of limbs, facial grimacing, torticollis, oculogyric crisis, and rhythmic protrusion of tongue, bulbar type of speech, trismus, or dystonic reactions resembling tetanus. Metoclopramide is secreted in human milk and its safety in infants has not been established. Neonates are less able to clear the drug from their systems hence dystonias and other extrapyramidal reactions are more common in this pediatric population than in adults [10]. Severe depression, seizures and intestinal discomfort have also been reported in infants that consume milk from mothers treated with metoclopramide [2, 11]. Other adverse effects additionally reported in mothers include anxiety, several gastrointestinal disorders and insomnia [2].
Domperidone use in human clinical trials has also been associated with varying findings. In some recent human data no maternal or neonatal adverse effects were reported [2]. Other studies have however reported adverse effects in mothers such as xerostomia, gastrointestinal disorders, cardiac arrhythmia, and sudden death but none in infants [2]. Domperidone is reported to also increase the risk of sudden cardiac death or could be linked with increased risk of prolonged QT syndrome (arrhythmia) [4].
Sulpiride and chlorpromazine are also typical antipsychotics that have been documented to be effective as galactagogues but are also associated with extrapyramidal reactions and weight gain. Human growth hormone and thyrotropin-releasing hormone are other agents have also been utilized to increase breastmilk production, but these agents have very limited clinical experience behind them [2, 7]. Oxytocin, although widely used in the past, has limited scientific data as a galactagogue also [7].
3.2 Botanical galactagogues
There are numerous references in literature for herbal medicines that are used to aid breastfeeding. However these are mainly based on empirical traditions with few human studies that show evidence that milk synthesis can be increased and that these are safe [2]. Most herbal galactagogues are believed to exert their pharmacologic effects through interactions with dopamine receptors, resulting in increased prolactin levels and there by augmenting milk supply [7]. Galactagogues are useful for women who are unable to produce breast milk on their own due to infant prematurity, illness of the mother or child, adoption, or surrogate motherhood [7].
The use of medicinal plants to stimulate breastmilk production has a long history of use [10] in almost all cultures over the world but has not been extensively studied nor fully exploited for use in lactating mothers [2]. The use of herbal medicines and phytonutrients or nutraceuticals to treat various conditions is expanding rapidly worldwide [12]. Botanical galactagogues may have the advantages of various claims of efficacy, preference of consumers for natural therapies, erroneous belief that herbal products are superior to manufactured products as well as dissatisfaction with the results, cost and side effects from the orthodox galactagogues [12]. A literature search on botanical galactagogues used within Ghanaian communities revealed a number of plants that are used for such purposes but with very little information and scientific studies to back their efficacy and safety.
4. Medicinal plants used as galactagogues
4.1 Amaryllidaceae
4.1.1 Allium sativum L.
A. sativum (garlic) is a perennial herb cultivated in various parts of the world and widely used as a food ingredient [13, 14]. Garlic has been used as a spice, food, and medicine for over 5000 years, and is one of the earliest documented herbs utilized for the maintenance of health and treatment of disease [15]. Garlic has many medicinal properties including, anti-microbial, anti-fungal, anti-viral, anti-protozoal, anti-inflammatory, anticancer and antioxidants [13, 14]. Garlic has traditionally been used to strengthen the immune system and gastrointestinal health. Today, this intriguing herb is probably the most widely researched medicinal plant [15]. Garlic is given for nutritional purposes to enhance gestation and lactation [16]. In a study conducted to evaluate the effectiveness of naturally prepared galactagogue mixtures containing garlic on breast milk production and prolactin levels in postnatal mothers, it was observed that the galactagogue mix increased prolactin production, confirming the folkloric use of garlic as a galactagogue [17]. Garlic is also known to impart odor and flavor to breast milk when consumed and infants tend to breast-feed longer on such milk [18].
Chemical constituents isolated from A. sativum were diallyl trisulfide (50.43%), diallyl disulfide (25.30%), diallyl sulfide (6.25%), diallyl tetrasulfide (4.03%), 1,2-dithiolane (3.12%), allyl methyl disulfide (3.07%), 1,3-dithiane (2.12%), and allyl methyl trisulfide (2.08%) [19]. The essential oil of A. sativum possessed contact toxicity against overwintering C. chinensis [19].
4.2 Annonaceae
4.2.1 Xylopia aethiopica A. rich
X. aethiopica is an evergreen tree with many-branched and narrow crown; it can grow from 15 to 30 m high. It is planted for medicinal purposes, as a shade tree and as an ornamental. The fruits are used as a tonic to improve women fertility and to aid delivery. Various parts of this plant are used across Ghana and Nigeria for various medicinal purposes. Powdered samples are taken or applied directly for use. The fruits also serve as a condiment, an emmenagogue, anthelmintic, antitussive, carminative and rubefacient. Xylopia is used generally for pain and in the treatment of bronchitis, asthma, arthritis, rheumatism, headache, neuralgia and colic pain [20, 21]. The seeds are ground and used as a galactagogue, emetic, rubefacient, stimulant and vermifuge [22]. The seeds are crushed and applied on the forehead for treating headache and neuralgia and its extract for round worm infestation and as a treatment for biliousness. Decoction of leaves serves as an emetic and is used against rheumatism. The powdered leaves are rubbed on the chest for treating bronchio-pneumonia and taken as snuff for treating headaches. Roots are powdered and applied to sores and also to treat cancer. Lactating mothers take the ground seed to increase milk flow. Fruits are particularly high in zinc content, perhaps the reason behind its consumption during lactation. The fruit contains xylopic acid, volatile oils, fixed oils, rutin and zinc. Compounds isolated from X. aethiopica include Lupeol, 16α-hydroxy-ent-kauran-19-oic acid, 3, 4′, 5-trihydroxy-6,6″-dimethylpyrano[2,3-g]flavone, 3-O-β-sitosterol β-D-glucopyranoside, isotetrandrine and trans-tiliroside [22, 23, 24].
4.3 Asclepiadaceae
4.3.1 Secamone afzelii (Roem. & Schult.) K. Schum
S. afzelii, is a familiar creeping woody climber found on fences, unkempt farm lands, on trees and grows to a very long length of about 2–3 cm. It is often seen as a nuisance to other plants because of its domineering spread wherever it grows. It is used in traditional medicine for stomach problems, diabetes, colic, dysentery and also for kidney problems. The whole plant boiled with rice is used as purgative for children. The decoction of the entire plant is prescribed for cough and catarrhal. For the treatment of gonorrhea, the whole plant is crushed with fresh palm nuts and oil [25]. A decoction of the whole plant is used as a galactagogue [26]. Studies have shown that S. afzelli has antimicrobial effects and also protect cells against damage by reactive oxygen species [27, 28, 29, 30]. The anti-inflammatory property of the leaf extract has also been demonstrated [30] in a murine model. Kaempferol-3-O-β-D-apiofuranosyl-(1 → 2)-α-L-rhamnopyranoside, rutin, myricetin 3-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside, kaempferol-3-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-galactapyranoside, mauritianin, and vicenin-2 have been isolated from S. afzelii [26]. The methanol extracts of S. afzelii is reported to be toxic in Artemia salina [31].
4.4 Costaceae
4.4.1 Costus afer Ker-Gawl
C. afer, natively called the bush sugar cane is classified as an endangered medicinal plant in Nigeria. It is a perennial, rhizomatous herb that can grow to a height up to 4 m. Leaves are arranged spirally, simple and entire [32]. It can be found in the forest belt of Senegal, South Africa, Guinea, Niger, Sierra Leone, Ghana, Cameroon and Nigeria [33]. C. afer is a useful medicinal plant that is highly valued for its antidiabetic, anti-inflammatory and anti-arthritic properties in South-East and South-West Nigeria, the plant extract is used as fodder to treat goats with retained placenta. The decoction of the stem or powdered fruits is used as a cough remedy. Its boiled root is applied to cuts and sores. A soothing formulation for rheumatic pains is prepared with the boiled leaves [33]. The leaves and stem are cut and crushed into smaller bits and boiled together with other plants such as Alchornea cordifolia, pawpaw, citrus species and the bark of Mangifera indica for the treatment of hunch back and malaria. Also the juice of C. afer is used as eye drop for inflammation and other eye defects. The young and tender leaves when chewed are believed to give strength to the weak and dehydrating patient. An infusion of the inflorescence is taken to treat stomach complaints. The stem or fruit decoction mixed together with sugarcane juice are taken to treat cough, respiratory problem and sore throat [32]. Alkaloids, saponins, flavonoids, anthraquinones, cardiac glycosides, terpenoids, phenolic compounds and tannins have been found to be present in the plant [33]. This plant contains diosgenin which is used as a precursor in the synthesis of a number of steroid drugs including corticosteroids, sex hormones, oral contraceptive and anabolic agents. The rhizome also contains saponins aferosides A–C, as well as diosein and parphyllin c and flavonoid glycoside kaempterol 3-0-rhamnopyranoside [34]. Extracts from the leaves exhibits antioxidant, hypolipidemic, hepatoprotective, anti-inflammatory, and analgesic, anticancer, antimicrobial, insecticidal and nematcidal activity and also contains verbascoside, which possesses antimicrobial activities [35]. Acute and chronic toxicity studies on C. afer showed no inherent toxic effects in animal models [35]. Liver function experiments of this plant in rats showed significant differences in the test groups when compared with the control while there was no significant effect on kidney function [33].
4.5 Euphorbiaceae
4.5.1 Euphorbia hirta L.
E. hirta is a slender-stemmed, annual hairy plant with many branches from the base to the top, spreading up to 40 cm in height. E. hirta is often used traditionally for female disorders, respiratory ailments (cough, coryza, bronchitis, and asthma), worm infestations in children, dysentery, jaundice, pimples, gonorrhea, digestive problems, diabetes and tumors. It is reported to contain alkanes, triterpenes, phytosterols, tannins, polyphenols, and flavanoids. The root exudate exhibits nematicidal activity [3]. The decoction of the dry herb is used for skin diseases while that for the fresh herbs is used as gargle for the treatment of thrush. Roots are also used for snake bites. This herb shows antibacterial, anti-inflammatory, anti-malarial, galactogenic, anti-asthmatic, anti-diarrheal, anti-cancer, anti-oxidant, anti-infertility, anti-amoebic, and anti-fungal activities [36]. The root decoction is also beneficial for nursing mothers deficient in milk [36]. E. hirta has shown a galactogenic activity in guinea pigs before puberty by increasing the development of the mammary glands and induction of milk secretion [36].
4.5.2 Euphorbia thymifolia wall
E. thymifolia is a softly hispid prostrate herb that is slender, cylindrical, pale green but often pink in color when fresh, becoming grayish green or dark purplish on drying. Stems are with white latex, spreading on the ground, 10–20 cm in length with a diameter from 1 to 3 mm [37]. E. thymifolia is traditionally used as a blood purifier, sedative, hemostatic, aromatic, stimulant, astringent in diarrhea and dysentery, anthelminthic, demulcent, laxative; and also in cases of flatulence, constipation; chronic cough; as an antiviral in bronchial asthma and paronychia. The dried leaves and seeds are given along with butter-milk to children in bowel complaints. Root is given in amenorrhea and gonorrhea. The oil is used as an insect repellant and in medicinal soaps for the treatment of erysipelas. It is also used as a vermifuge for dogs and farm foxes. Plant juice is employed in southern India as a cure for ring worms. The plant powder is given with wine as a remedy for bites of venomous reptiles. It is applied on the scalp with ammonium chloride to cure of dandruff. The fresh plant is considered vulnerary and used in ophthalmia and other eye troubles, ardor, sores, atrophy, dysentery and breast pain [24]. This plant is reported to be used as a galactagogue both in West-Africa and in India [24, 38].
4.5.3 Hymenocardia acida Tul
H. acida is a small tree of about 6 m high, gnarled and twisted with characteristic rough, rusty-red bark. It is widespread in tropical Africa [39]. The leaves of Hymenocardia acida are commonly used in Northern Nigeria alone or in combination with other plant parts to manage sickle cell disease. The plant contains carbohydrates, tannins, flavonoids, saponins, alkaloids, cardiac glycosides, resins, steroids and terpenes [38]. The root of this plant is reported to be used within West-Tropical Africa to stimulate lactation but [24] there are however anecdotal reports that this plant it is also given to diminish breastmilk supply. Ethnopharmacological studies of H. acida revealed an extensive array of medicinal uses, particularly from tropical African countries. In Senegal and Ivory Coast, an infusion or decoction of its leaves is used for the treatment of chest complaints, small pox, in baths and draughts as a febrifuge, and is taken as snuff for headaches or applied topically for rheumatic pains and toothaches. The bark and leaves are prescribed together with other plants in various ways in Nigeria for abdominal and menstrual pains and as poultices to treat abscesses and tumors. The powdered leaves of this tree are also used for the treatment of arthritis. Pharmacological activities reported on the plant include anti-ulcer, anti-plasmodial and cytotoxic activities [39].
4.5.4 Plagiostyles africana Prain exDe wild
P. africana trees grow in the lowland rainforest of south Nigeria and West Cameroons extending to Zaïre (the Democratic Republic of Congo). It reaches 16 m tall by 1.30 m in girth. The wood is light yellowish white and it is cut in Gabon to make spoons, combs and hair-pins. A wood-decoction is taken in the belief that it promotes milk-production [24]. The bark contains a white to yellowish viscid latex. The bark is used for chest-affections, and for fever [40].
4.5.5 Ricinus communis L.
R. communis (castor oil plant) is a perennial shrub whose leaves have long petiole and palm like lobed blades. Fruit is three chambered, globose capsule with soft spines. When capsules mature, they split up into three cavities and the seeds are expelled out [41]. This plant is grown worldwide for the production of castor oil. R. communis exhibits various biological and pharmacological activities such as abortifacient effect, acid phosphatase inhibition, acid phosphatase stimulation, agglutin activity, alkaline phosphatase inhibition, anti-conceptive activity, anti-diabetic activity, anti-infertility effects anti-inflammatory activity, antimicrobial activity, antioxidant activity, free radical scavenging activity, hepatoprotective activity, insecticidal activity and repellent properties [5, 41]. Castor oil is massaged over the breast after child-birth to increase the flow of milk as it stimulates the mammary glands. The leaves of castor can also be used to foment the breast for the same purpose [5, 24].
4.6 Leguminosae
4.6.1 Tamarindus indica L.
The tamarind (T. indica) is a common tree, especially in West Africa [42] and India. It is a moderate to large sized, evergreen tree that grows up to 24 m in height and 7 m in girth. T. indica has antimicrobial, antioxidant, anti-venom properties and it is also used as a galactagogue [43]. It is indigenous to tropical Africa and is also cultivated in subtropical China, India and Spain. Initially, the fruit shows a reddish-brown color that turns black brown, becoming more aromatic and sour on ripening. The fruit pulp is used for seasoning, as a food component and in juices. T. indica has antimicrobial, antioxidant, anti-venom properties and also used as a galactagogue [43]. Tamarind is most commonly used as a laxative and in the treatment of wounds and abdominal pains, followed by diarrhea, helminth infections, fever, malaria, aphrodisiac, respiratory problems and dysentery [42]. Its fruit is regarded as a digestive, carminative, laxative, expectorant and blood tonic [44]. Other parts of the plant have anti-oxidant [45], anti-hepatotoxic [46], anti-inflammatory, anti-mutagenic, anti-cancer, anti-ulcer and anti-diabetic [47] activities. The flower and leaf are eaten as vegetables, while the germ obtained from the seed is used for manufacturing tamarind gum which is well-known as a component of jelly [5, 48]. Toxicity study in rat modules showed that tamarind pulp extract was generally safe and well tolerated at 5, 200, 1000 mg/kg body weight per day for 6 months [49].
4.6.2 Acacia nicolita var. adansonaii (Guill. & Perr.) Brenan
A. nicolita also known as gum Arabic occurs as a tree which can grow up to about 50 feet high. It has a dark brown bole with deeply fissured bark. The leaves are compound and alternately arranged with about 10 to 30 elliptical pubescent leaflets on each leaf. The flowers occur as round, yellow heads situated at the end of branches. Fruits are thick, gray and are well constricted hairy pods [50]. Various parts of A. nicolita have been used for the treatment of various cancers in Western Africa. These include cancers of the ear, eye and testicles. Roots of the plant are used to treat tuberculosis, its wood for the treatment of smallpox, and the leaves for the treatment of ulcers [51]. In the Katsina state of Nigeria, decoction of the pod is used for postpartum wound healing [52] and here also the young shoots and pods are used to stimulate lactation [53]. When the effect of the aqueous extract of A. nicolita was investigated on milk production in rats, it was observed that, the extract was able to significantly stimulate the release of prolactin. Also, it was observed that the mammary glands of estrogen-primed rats treated with the extract showed clear lobuloalveolar development with milk secretion [54]. Present in A. nicolita are tannins, flavonoids, alkaloids, fatty acids and terpenes have been isolated from various parts of the plant. This plant is also known to have anti-inflammatory, anti-oxidant, anti-diarrheal, anti-hypertensive and anti-spasmodic, anti-bacterial, anti-helminthic, anti-platelet aggregatory, and anti-cancer activities [50]. Toxicological studies on A. nicolita showed that it has a low toxicity potential [55]. However it is also reported that repeated administration of doses higher than 250 mg/kg body weight for 28 days caused hepatotoxicity in rats [56].
4.6.3 Desmodium adscendens (Sw.) DC
D. adscendens is a herbaceous non-climbing perennial shrub that commonly occurs in tropical areas of Africa, South America, Asia, Australia and Oceania [57]. The plant thrives in varying habitats ranging from forests to grasslands and in secondary/disturbed vegetation. A decoction of the leave and stem is used for asthma and other diseases associated with smooth muscle contraction and epilepsy in Ghana [57]. It is used for the treatment of fever, pain and epilepsy in the Congo. In Brazil the plant is used in the treatment of ovary inflammation. It is used in Ghana to enhance lactation [22]. D. adsendens contains indole alkaloids, unsaturated fatty acids, tyramine, hordenine and saponins [58, 59]. Triterpenoid saponins, tetrahydroiso-quinolones, phenylethylamines and indole-3-alkyl amines have been isolated from the leaves [60]. D. adscendens causes dilation, relaxation of smooth muscles, anti-histamine effects and normalizes elevated liver enzyme levels [58].
4.7 Malvaceae
4.7.1 Hibiscus sabdariffa Linn
H. sabdarriffa commonly known as Roselle (English), Sobolo (Akan Ghanaian language) is widely cultivated among the tropical and subtropical regions of the world. These include some parts of Asia and West Africa. This plant was domesticated by natives of Western Sudan before 4000 BC [61]. The plant is an erect herbaceous annual and a shrub that can grow up to about 2 m in height. It consists of smooth cylindrical and typically red stems. The leaves are simple, deeply lobed, petiolate and alternately arranged with reddish reticulate veins. The flowers occur singly in the axils of the leaves. The calyces are typically red and made up of five sepals fused at the base which become fleshy and juicy upon maturity [62, 63].
The main class of phytochemicals present in H. sabdariffa is anthocyanins and flavonoid, as well as organic acids and polysaccharides. Citric acid, malic acid, tartaric acid and ascorbic acid are also present [64]. Some flavonoids that have been described in H. sabdariffa extracts include hibiscitrin, sabdaritrin, gossytrin and gossypitrin [65, 66]. Different parts of H. sabdariffa are used for various medicinal purposes. The calyces of the flower are commonly incorporated in hot and cold drinks due to its pleasing taste. In many parts of Africa, it has been used for its spasmolytic, antioxidant [67, 68, 69], antibacterial [70, 71], antipyretic [72], diuretic and anthelmintic properties [73]. It is also used for the treatment of high blood pressure and liver diseases. Additionally to their medicinal uses, various parts of the plants are incorporated in meals and used for other culinary purposes. In some cultures, H. sadariffa is included in some herbal mixtures and consumed by nursing mothers to increase milk supply [74]. In Nigeria also, the decoctions of the seeds have been reported to be used to increase lactation in cases of poor milk supply [75]. In 66 healthy mothers who took extracts of hibiscus, fennel, fennel oil, verbena, raspberry leaves, fenugreek and vitamin C, there was an increase in breastmilk production by the third day [76]. Toxicity studies have shown that the prolonged usage of the aqueous-methanolic extract of H. sabdariffa calyces at the dose of 250 mg/kg could cause liver injury in rats [77]. Also, the 12-week subchronic effect of H. sabdariffa calyx aqueous extract at the doses of 1.15, 2.30, and 4.60 g/kg induced testicular toxicity [78].
4.7.2 Gossypium herbaceum L. (Malvaceae)
G. herbaceum is an erect, shrubby, hairy plant that grows up to 2–8 m high [79]. The decoction of this plant is used traditionally across West Africa as an aphrodiasiac, galactagogue, spermatogenic, expectorant, laxative, demulcent, emenagogue, dysmenorrhea, and for the expulsion of retained placenta [80, 81]. In human studies G. herbaceum was shown to be efficacious, safe and cost effective in augmenting lactation in perceived insufficient milk supply [9]. This plant is known to contain carbohydrates, tannins, saponins, steroids, glycosides, phenolics, sitosterol, ergosterol, lipids, gossypol, oleic, palmitic and linoleic acid [79]. Extracts from this plant and it active constituents gossypol have shown anti-cancer, anti-infertility, anti-malarial, anti-oxidant, anti-trypanosomal, anti-viral, anti-microbial, anti-viral, hepatoprotective and anti-depressant activities in animal models [16, 82, 83].
4.8 Moraceae
4.8.1 Milicia excelsa (Welw.) C.C. Berg
M. excelsa is commonly known as odum or iroko in Ghana. It is a large, dioecious tree that grows up to 50 m high [84]. This plant is widely used in African folk medicine as a decoction to treat several ailments. A root decoction is taken to treat female sterility. A decoction of the root and stem bark is taken as an aphrodisiac. The extracts from the bark are taken to treat cough, asthma, heart trouble, lumbago, spleen pain, stomach pain, abdominal pain, edema, ascites, dysmenorrhea, gonorrhea, general fatigue, rheumatism, sprains, and as a galactagogue, aphrodisiac, tonic and purgative. Also the stem bark preparations are topically applied to treat scabies, wounds, and loss of hair, fever, venereal diseases and sprains. They are applied as an enema to cure piles, diarrhea and dysentery. The latex is applied on burns, wounds, sores, eczema and on other skin problems as well as taken to treat type 2 diabetes [85, 86]. Additionally, it is taken against stomach problems, hypertension, tumors, and obstruction of the throat and as a galactagogue [87]. Leaves are eaten to treat insanity; a leaf maceration is drunk as a galactagogue. A decoction of the leaves is taken for the treatment of gallstones. Leaf preparations are externally applied to treat snakebites and fever and as eye drops to treat filariasis. Alkaloids, flavonoids and saponins are present as well as triterpenes and glycosides [79, 88]. The leaf extract of M. excelsa is reported to be safe in rodents [79, 89, 90].
4.8.2 Ficus sp. L.
Ficus species comprises one of the largest genera of angiosperms with more than 800 species of trees, shrubs, hemiepiphytes, climbers, and creepers in the tropics and subtropics worldwide [91]. The bark, root, leaves, fruit and latex of this plant are frequently used for the treatment of various illnesses including gastro-intestinal, liver, venereal, respiratory, metabolic and cardiovascular disorders. It is used in traditional medicine as a galactagogue [92]. The fresh juice (50–100 ml) of leaves of F. racemosa L. is given with water for about 10 days to treat gastrointestinal problems. Bark of F. arnottiana and F. hispida shows hypoglycaemic activity. Roots of F. bengalensis show anthelmintic activity. This extract is also reported to inhibit insulinase activity from liver and kidney. Fruit extracts exhibits anti-tumor activity. Various pharmacological actions such as anti-ulcer, anti-diabetic, lipid lowering and antifungal activities have been described for F. exasperata. Ethanolic leaf extract of F. exasperata shows anti-bacterial activity. Leaves exhibit hypotensive activity. Ethanolic and aqueous wood extracts of F. glomerata shows Anti-HIV-1 integrase activity. F. religiosa is reported to be used for the treatment of asthma, cough, sexual disorders, diarrhea, hematuria, ear-ache and toothache, migraine, eye troubles, gastric problems and scabies; leaf decoction has been used as an analgesic for toothache; fruits for the treatment of asthma, other respiratory disorders and scabies; stem bark is used in gonorrhea, bleeding, paralysis, diabetes, diarrhea, bone fracture, antiseptic, astringent and antidote. Fruit of F. carica shows spasmolytic activity, mediated through the activation of K+-ATP channels along with anti-platelet activity. Hence, it can be used in gut motility and inflammatory disorders [93]. Most species of Ficus contain phenolic compounds, organic acids, and volatile compounds [91]. Some species have been reported not to be toxic in rodents [93].
4.9 Musaceae
4.9.1 Musa paradisiaca L.
M. paradisiaca is an herbaceous plant that grows up to about 9 m with a robust treelike false-stem. The unripe fruits and juice of M. paradisiaca is used in folk medicine to treat and manage diarrhea, dysentery, cholera, intestinal lesions, ulcerative colitis, diabetes, sprue, uremia, nephritis, gout, hypertension, cardiac disease, otalgia and hemoptysis [94, 95]. The flowers are also employed in treating dysentery, diabetes and menorrhagia [94]. The root is also used traditionally as an anthelmintic [95], for treating blood disorders and venereal diseases [94]. It is also used as an anti-inflammatory, analgesic and anti-dote for snakebites [96].
The green fruits of M. paradisiaca has been reported to possess anti-hypertensive [97] as well as hypoglycemic effect due to effects on insulin production and glucose utilization [98]. M. paradisiaca inhibits cholesterol crystallization in vitro [99]. M. paradisiaca has also been shown to induce atherosclerosis [100]. There have been reports of the potential of M. paradisiaca flower to enhance milk production of nursing rats [101, 102]. Serotonin, nor-epinephrine, tryptophan, indole compounds, tannin, starch, iron, crystallisable and non-crystallisable sugars, vitamins, albuminoids, fats, mineral salts have been found in the fruit pulp of M. paradisiaca [94] with several other compounds that have been isolated and identified from various parts of the plant [103].
4.10 Ranunculaceae
4.10.1 Nigella sativa L.
N. sativa is a small herb of about 45 cm long with linear-lanceolate leaves and a pale blue flower. It is used as a food and medicine frequently to treat a variety of health conditions pertaining to the respiratory system, digestive tract, kidney and liver functions, cardiovascular system, and immune system support, as well as for general well-being [104] and as a galactagogue [105].
Phytochemical analysis has revealed the presence of nigelline, nigellicine, nigelimine, nigellimine-N-oxide, avenasterol-5-ene, avanasterol-7-ene, campesterol, cholesterol, citrostadienol, cycloeucalenol, sitosterol, stigmasterol, stigmastanol, 24-ethyl-lophenol, obstafoliol [105]. This plant is reported to have anti-cancer, anti-microbial, analgesic, antipyretic, contraceptive and anti-fertility, anti-oxytocic, anti-tussive, anti-inflammatory, and anti-oxidant potentials. Anti-cancer activity has been demonstrated for blood, breast, colon, pancreatic, liver, lung, fibrosarcoma, prostate, and cervix cancer cell lines and in animal models as well [106, 107, 108, 109]. Toxicological studies showed no toxic effect in rodents [105].
4.11 Solanaceae
4.11.1 Solanum torvum Swartz
S. torvum is an evergreen, widely branched, prickly shrub that grows up to 5 m tall [110]. The fruits of S. torvum are edible and commonly available in the markets for incorporation into stews and soups across West-Africa. A decoction of the fruits is given for cough ailments and is considered useful in cases of liver and spleen enlargement. The plant is used as a sedative and diuretic and the leaves are used as a hemostatic. The ripened fruits are used in the preparation of tonic and hemopoietin agents and also for the treatment for pain. It has antioxidant properties. It is intensively used worldwide in traditional medicine as a poison anti-dote and for the treatment of fever, wounds, tooth decay, reproductive problems and arterial hypertension [17, 111, 112, 113]. S. torvum fruits are reported to contain alkaloids, flavonoids, saponins, tannins, glycosides, fixed oil, vitamin B group, vitamin C and iron salts. It also has number of chemical constituents like neochlorogenin 6-O-β-D-quinovo-pyranoside, neochlorogenin 6-O-β-D-xylopyranosyl-(1 → 3)-β-D-quinovopyranoside, neochlorogenin 6-O-α-L-rhamnopyranosyl-(1 → 3)-β-Dquinovopyranoside, sola-genin 6-O-β-D-quinovopyranoside, solagenin 6-O-α-Lrhamnopyranosyl-(1 → 3)-β-D-quinovopyranoside, isoquercetin, rutin, kaempferol and quercetin [16, 113, 114]. S. torvum also possesses antimicrobial, antiviral, immuno-secretory, antioxidant, analgesic, anti-inflammatory, anti-ulcerogenic activities, cardiovascular, nephroprotective, antidiabetic, angiotensin and erotonin receptor blocking activities [110]. It is reported to be used in a concoction to nourish pregnant and lactating mothers with vitamins and proteins and to enhance lactation [115].
4.12 Verbanaceae
4.12.1 Lippia multiflora Moldenke
L. multiflora is an aromatic, perennial plant with woody stems growing up to 3 m high [53]. The plant is locally harvested in Ghana and Benin and the leaves are steeped in hot water for tea. It is used in the treatment of stomach aches, nausea and fever. The leaves and immature flowering stems have anti-biotic, laxative and vermifuge activities [116]. The leaves contain limonene, a-caryophyllene, trans-farnesene, caryophyllene oxide and farnesol [117]. Tea infusion of plant is used for the treatment of arterial hypertension in Ghana [118]. A herbal extract of the plant exhibits anti-malarial, anti-microbial, anti-inflammatory, diuretic, laxative, muscle relaxant and is also used in lactation failure [22]. Lippia oil is effective topically gram-negative bacteria [117] and body lice, head lice, scabies’ mites [119]. This plant possesses a tranquilizer and analgesic activities as diazepam [118].
4.13 Zingiberaceae
4.13.1 Aframomum melegueta (Roscoe) K. Schum
A. melegueta is commonly known as grains of paradise or alligator pepper. It is a spicy edible perennial fruit which grows to about 1 m high. A. melegueta produces reddish-brown seeds, which have a strong aromatic flavor and a pungent taste. These seeds are widely employed as spices and it is also an ingredient in numerous West African ethno medical practices. A. melegueta is a remedy for a number of diseases such as constipation, rheumatic pains and fever [120, 121]. The medicinal uses of A. melegueta also include its use as an aphrodisiac, measles and leprosy. It is also taken to treat excessive lactation, post partem hemorrhage, purgation and used as a galactagogue, anthelmintic and hemostatic [122]. A. melegueta exhibits anti-inflammatory, anti-oxidant and anti-tumor effects [123, 124] as well as anti-protozoal activity against schistosomes [22]. The phytochemical constituents are essential oils—such as gingerol, shagaol, paradol. Alkaloids, flavonoids, saponins, tannins, cardiac glycosides, terpenoids, steroids [125] as well as essential oils and resins have also been identified in this plant [126]. The LD₅₀ of 273.86 mg/kg body weight and lower than normal hemoglobin and red blood cells in animal studies seems to confirm the possibility of toxicity from this plant [125].
5. Conclusion
There are numerous references in literature for herbal medicines use to aid breastfeeding. However, the use of herbal galactagogues is mainly based on empirical traditions with little scientific data. With increase in the complexity of breastfeeding, it is imperative that these herbal galactagogues be studied. There is a need to standardize the herbal galactagogues, investigate their nutritional and phytochemical composition as well as conduct clinical trials to generate scientific evidence of their efficacy and safety, as a basis for commercial production and usage. Conducting pharmacodynamics and pharmacokinetic studies will also play a vital role in determining their metabolism in the mother and neonate. Their mechanism of action will also need to be investigated. These herbs will have the advantages of being easily available, cheaper and more tolerable to both mother and neonate.
Acknowledgments
The authors are grateful to the staff of the Ghana Herbarium for making available published literature on some of the medicinal plants.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"galactagogues, lactation, breastfeeding, medicinal plants",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/64667.pdf",chapterXML:"https://mts.intechopen.com/source/xml/64667.xml",downloadPdfUrl:"/chapter/pdf-download/64667",previewPdfUrl:"/chapter/pdf-preview/64667",totalDownloads:1640,totalViews:389,totalCrossrefCites:2,totalDimensionsCites:3,totalAltmetricsMentions:0,impactScore:2,impactScorePercentile:82,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"July 26th 2018",dateReviewed:"October 23rd 2018",datePrePublished:"December 14th 2018",datePublished:"June 19th 2019",dateFinished:"December 5th 2018",readingETA:"0",abstract:"The recommended diet for human infants within the first 6 months of life is breast milk. No other natural or artificial formulation has been able to match up to this gold standard. Mothers who have attempted to pursue exclusive breastfeeding can, however, attest to numerous nutritional and non-nutritional challenges mainly resulting in insufficient milk production (hypogalactia) or the absence of milk production (agalactia). There are very few and officially recommended orthodox drugs to increase lactation. The most widely used galactagogues being chlorpromazine, sulpiride, metoclopramide and domperidone are associated with very high incidences of unpleasant side effects including their extra-pyramidal effects in both mother and infant. There is therefore a need to keep searching for more acceptable galactagogues. This section reviews current literature on medicinal plants used within the local Ghanaian community to enhance lactation. Various electronic databases such as PubMed, Science Direct, SciFinder and Google Scholar as well as published books on Ghanaian medicinal plants were searched. A total of 22 plants belonging to 13 families were reviewed with regards to their medicinal values, information on lactation and toxicity.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/64667",risUrl:"/chapter/ris/64667",book:{id:"8290",slug:"pharmacognosy-medicinal-plants"},signatures:"Emelia Oppong Bekoe, Cindy Kitcher, Nana Ama Mireku Gyima, Gladys Schwinger and Mark Frempong",authors:[{id:"186992",title:"Dr.",name:"Emelia Oppong",middleName:null,surname:"Bekoe",fullName:"Emelia Oppong Bekoe",slug:"emelia-oppong-bekoe",email:"emekisseih@yahoo.co.uk",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"280851",title:"Dr.",name:"Cindy",middleName:null,surname:"Kitcher",fullName:"Cindy Kitcher",slug:"cindy-kitcher",email:"cindyasare@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"280852",title:"Dr.",name:"Nana Ama",middleName:null,surname:"Mireku-Gyimah",fullName:"Nana Ama Mireku-Gyimah",slug:"nana-ama-mireku-gyimah",email:"namgyimah@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"280854",title:"Dr.",name:"Mark",middleName:null,surname:"Frimpong",fullName:"Mark Frimpong",slug:"mark-frimpong",email:"mfrimpong@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"280855",title:"Dr.",name:"Gladys",middleName:null,surname:"Schwinger",fullName:"Gladys Schwinger",slug:"gladys-schwinger",email:"odeyschwinger@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Challenges with breastfeeding",level:"1"},{id:"sec_3",title:"3. Solutions to breastfeeding challenges",level:"1"},{id:"sec_3_2",title:"3.1 Synthetic galactagogues",level:"2"},{id:"sec_4_2",title:"3.2 Botanical galactagogues",level:"2"},{id:"sec_6",title:"4. Medicinal plants used as galactagogues",level:"1"},{id:"sec_6_2",title:"4.1 Amaryllidaceae",level:"2"},{id:"sec_6_3",title:"4.1.1 Allium sativum L.",level:"3"},{id:"sec_8_2",title:"4.2 Annonaceae",level:"2"},{id:"sec_8_3",title:"4.2.1 Xylopia aethiopica A. rich",level:"3"},{id:"sec_10_2",title:"4.3 Asclepiadaceae",level:"2"},{id:"sec_10_3",title:"4.3.1 Secamone afzelii (Roem. & Schult.) K. Schum",level:"3"},{id:"sec_12_2",title:"4.4 Costaceae",level:"2"},{id:"sec_12_3",title:"4.4.1 Costus afer Ker-Gawl",level:"3"},{id:"sec_14_2",title:"4.5 Euphorbiaceae",level:"2"},{id:"sec_14_3",title:"4.5.1 Euphorbia hirta L.",level:"3"},{id:"sec_15_3",title:"4.5.2 Euphorbia thymifolia wall",level:"3"},{id:"sec_16_3",title:"4.5.3 Hymenocardia acida Tul",level:"3"},{id:"sec_17_3",title:"4.5.4 Plagiostyles africana Prain exDe wild",level:"3"},{id:"sec_18_3",title:"4.5.5 Ricinus communis L.",level:"3"},{id:"sec_20_2",title:"4.6 Leguminosae",level:"2"},{id:"sec_20_3",title:"4.6.1 Tamarindus indica L.",level:"3"},{id:"sec_21_3",title:"4.6.2 Acacia nicolita var. adansonaii (Guill. & Perr.) Brenan",level:"3"},{id:"sec_22_3",title:"4.6.3 Desmodium adscendens (Sw.) DC",level:"3"},{id:"sec_24_2",title:"4.7 Malvaceae",level:"2"},{id:"sec_24_3",title:"4.7.1 Hibiscus sabdariffa Linn",level:"3"},{id:"sec_25_3",title:"4.7.2 Gossypium herbaceum L. (Malvaceae)",level:"3"},{id:"sec_27_2",title:"4.8 Moraceae",level:"2"},{id:"sec_27_3",title:"4.8.1 Milicia excelsa (Welw.) C.C. Berg",level:"3"},{id:"sec_28_3",title:"4.8.2 Ficus sp. L.",level:"3"},{id:"sec_30_2",title:"4.9 Musaceae",level:"2"},{id:"sec_30_3",title:"4.9.1 Musa paradisiaca L.",level:"3"},{id:"sec_32_2",title:"4.10 Ranunculaceae",level:"2"},{id:"sec_32_3",title:"4.10.1 Nigella sativa L.",level:"3"},{id:"sec_34_2",title:"4.11 Solanaceae",level:"2"},{id:"sec_34_3",title:"4.11.1 Solanum torvum Swartz",level:"3"},{id:"sec_36_2",title:"4.12 Verbanaceae",level:"2"},{id:"sec_36_3",title:"4.12.1 Lippia multiflora Moldenke",level:"3"},{id:"sec_38_2",title:"4.13 Zingiberaceae",level:"2"},{id:"sec_38_3",title:"4.13.1 Aframomum melegueta (Roscoe) K. Schum",level:"3"},{id:"sec_41",title:"5. Conclusion",level:"1"},{id:"sec_42",title:"Acknowledgments",level:"1"},{id:"sec_42",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Hoddinott P, Tappin D, Wright C. 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Ethnobotany of the Sumu (Ulwa) of southeastern Nicaragua and comparisons with Miskitu plant loreLa EtnobotÁNica de los Sumu (Ulwa) del Sudeste de Nicaragua y Comparaciones con El saber BotÁNico De los Miskitus. Economic Botany. 1999;54(3):363-386'},{id:"B97",body:'Osim EE, Ibu JO. The effect of plantains (Musa paradisiaca) on DOCA-induced hypertension in rats. Pharmaceutical Biology. 1991;29(1):9-13'},{id:"B98",body:'Ojewole JAO, Adewunmi CO. Hypoglycemic effect of methanolic extract of Musa paradisiaca (Musaceae) green fruits in normal and diabetic mice. Methods and Findings in Experimental and Clinical Pharmacology. 2003;25(6):453-456'},{id:"B99",body:'Saraswathi NT, Gnanam FD. Effect of medicinal plants on the crystallization of cholesterol. Journal of Crystal Growth. 1997;179:611-617. DOI: 10.1016/S0022-0248(97)00172-3'},{id:"B100",body:'Parmar HS, Kar A. 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Department of Pharmacognosy and Herbal Medicine, School of Pharmacy, University of Ghana, Ghana
Department of Obstetrics and Gynecology, University Hospital, Ghana
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1. Introduction
The human organism is a dynamic, deterministic, non-linear system that shows a sensitive dependence on initial conditions. The amount of cells in the human body is extraordinarily large. A study carried out by Eva Bianconi with collaborators from Italy, Greece and Spain, concluded with the number of 3.72 ± 0.81 × 1013, or approximately 37 trillion cells. There is already an estimate of the amount of cells that need to be removed daily in a healthy human adult, seeking to maintain the body’s stability. That number reaches the extraordinary value of 150 billion cells a day! If we remember that the total amount of cells is approximately 37.2 trillion, we conclude that, per day, a healthy human individual loses 0.4% of its cell mass [1].
It is inferred, then, that for the maintenance of life through the proper, harmonious and stable functioning of these cells, in addition to the restoration of lost elements, it is mandatory to spend energy. The clinical concept that refers to this condition of maintenance of conditions of stability is Alostasia. Through Alostasia, Homeostasis is maintained.
The name Homeostasis was created by Walter B. Cannon, in 1932. Literally translated, homeostasis means “staying the same”, but this is not entirely accurate. In reality, homeostasis is not a static state; rather, it is a dynamic state.
In biology, homeostasis is classical, the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid balance, being kept within certain pre-set limits, and which we will call from now on, as the Homeostatic Level.
One of the fundamental elements for the control of the Homeostatic Level is the Autonomic Nervous System (ANS), with its different components, the sympathetic nervous system, the parasympathetic nervous system and the enteric nervous system [2].
The effects of aging on the autonomic nervous system are multiple and vary between and within both sympathetic and parasympathetic portions. Normal human aging is associated with changes in autonomic control of several bodily functions, particularly those served by cardiovascular and thermoregulatory systems [3].
The assessment of the autonomic nervous system has been possible through the quantification of a biological marker called Heart Rate Variability (HRV). The literature is extremely rich in studies on HRV, and its high applicability in terms of diagnosis and prognosis is a consensus.
It is possible to study HRV in different domains, namely time, frequency and non-linear. In these domains, different variables have already been described, each with its greater or lesser sensitivity.
Briefly, however, we can highlight three of them among those with the greatest clinical applicability: heart rate (HR), the root-mean-square of successive differences between adjacent normal RR intervals in a time interval (RMSSD) and the HF band representing the power in the frequency range between 0.15 and 0.4 Hz (HFms2) [4].
2. Heart rate
Resting heart rate has ceased to be just another vital sign and has become a relevant cardiovascular risk marker. It has long been known that life span is inversely related to resting heart rate in most organisms. The classic article by Levine [5], shows the existence of an inverse semilogarithmic relation between heart rate and life expectancy among mammals, suggesting a predetermined number of heart -beats in a lifetime, with a magic average number of 7.3 ± 5.6 × 108 heart-beats/lifetime.
Boudoulas KD et al. [6], make an excellent review relating heart rate, life expectancy and the cardiovascular system. They conclude that many factors regulate heart rate, and it may be these factors, rather than the heart rate itself, which determine survival, but heart rate has multiple direct effects on the cardiovascular system, regardless of the regulatory mechanisms. These effects directly affect the cardiovascular system in multiple ways that, in turn, may affect survival.
From a pathophysiological point of view, the main finding is that resting heart rate is associated with shear and endothelial function in humans [7].
The impact of increased resting heart rate on prognosis is validated in the general population in patients with hypertension, coronary artery disease, or heart failure and irrespective of age, cardiovascular risk factors, or comorbidities, although there is still no definitive confirmation of the prognostic effect of heart rate reduction with the use of drugs such as ivabradine, on primary combined events [8].
3. RMSSD
RMSSD is the root-mean-square of successive differences between adjacent normal RR intervals in a time interval, expressed in millisseconds, and is the primary time domain measure used to assess parasympathetic sources of HRV [4].
Several studies have shown a reduction in RMSSD values in the presence of disease or aging, reflecting a reduction in heart rate variability. Maurer CW et al., in 2016 [9], evaluated the behavior of the autonomic nervous system in 35 patients with functional movement disorders (FMD) compared to 38 healthy controls. They found a significant reduction in RMSSD in patients with FMD (P = 0.02), as well as an increased mean heart rate (P = 0.03), concluding that decreased vagal tone may reflect increased stress vulnerability in patients with FMD.
DeGiorgio, CM et al. [10], studied 19 subjects with intractable partial seizures, at least three per month, in a randomized clinical trial of omega-3 fatty acids in epilepsy. They looked for whether or not there was a correlation between heart rate variability and the estimated risk of Sudden Unexplained Death in Epilepsy, quantified by the SUDEP-7 Inventory. They found that the RMSSD was inversely correlated with the SUDEP-7 score, r = −0.64, p = 0.004. Subjects with higher SUDEP-7 scores had reduced levels of HRV (RMSSD). Other time-dependent measures of HRV (SDNN, SDANN) were not significantly correlated with SUDEP risk scores.
In another study, Maheshwari A et al. [11] evaluated a large group of 12,543 individuals from the general population, participating in The Atherosclerosis Risk in Communities Study. They were looking for a relationship between low HRV and sudden cardiac death (SCD). During a median follow-up of 13 years, 215 SCDs were identified. In the group in which sudden deaths occurred, there was a statistically significant difference in heart rate (70.3 ± 13.8 bpm versus 67.7 ± 10.3 bpm; P = 0.008) and in HF power ms2 (1.6 ± 1.5 Ln versus 2.1 ± 1.3 Ln; P < 0.0001). As for the RMSSD, there was no statistically significant difference between the groups, but in both conditions, the values were below the ideal values for normality (27.3 ± 28.3 ms versus 29.2 ± 23.3 ms; P = 0.25).
Based on the knowledge that sepsis is associated with marked alterations in hemodynamic responses, autonomic dysfunction and impaired vascular function, Bongiorno Junior et al. [12], explored the prognostic utility of cardiac output (CO), stroke volume (SV), indices of vagal modulation (RMSSD and SD1), total heart rate variability (HRV) and flow-mediated dilation (FMD) of the brachial artery (%FMD) in 60 patients recruited at an intensive care unit. They found that in the group of 39 patients who did not survive, HR was higher (105 ± 27 bpm versus 84 ± 15 bpm; P = 0.02) and it was observed that the RMSSD and SD1 indices could be predictors of endothelial function and RMSSD could predict the risk of death in these patients.
The ROC Curve of RMSSD was useful in predicting 28-day mortality in patients with sepsis. The area under the curve was 0.784 (0.656–0.881). The value of 10.8 ms was chosen as the cut-off point for RMSSD (sensitivity of 77.1%, specificity of 73.9%, the positive likelihood ratio of 2.96 and negative likelihood ratio of 0.31. With RMSSD ≤10.8 ms, the mean survival time was 23.1 days and with RMSSD>10.8 ms, the mean survival time was 23.1 days).
4. HF ms2
There are three main spectral components in an HRV spectrum named as high frequency (HF), low frequency (LF), and very low frequency (VLF) bands. The HF band represents the power in the frequency range between 0.15 and 0.4 Hz. HF power is generally believed to represent respiration-linked changes in heart rate and is generally accepted as a measure of respiratory sinus arrhythmia (RSA), or the parasympathetic contribution to HRV. RSA refers to the acceleration in heart rate that occurs during inspiration (due to the cardiovascular control center’s inhibition of vagal outflow) and the subsequent heart rate deceleration that occurs during expiration, due to vagal restoration [13, 14].
Doheny et al. in 2015 [15], evaluated the possibility of using a non-invasive biomarker that allows early detection of patients at risk of necrotizing enterocolitis (NEC), that is an acute neonatal inflammatory disease that may lead to intestinal necrosis, multi-system failure and death. For that, they used the high frequency (HF) component of heart rate variability. They studied 70 stable preterm infants (gestational age 28-35 week). HF ms2 was 21.5 ± 2.7 ms2 in infants that remained healthy and 3.9 ± 0.81 ms2 in those that later developed stage 2 + NEC (P < 0.001). The cut-off value in the ROC curve was 4.68ms2, predictive for developing NEC with sensitivity and specificity of 89% and 87%, and positive and negative predictive values of 50% and 98%, respectively. They concluded that HF ms2 may serve as a potential, non-invasive predictive biomarker of NEC-risk in infants.
In 2004, Abramkin et al. [16], studied 188 patients to compare the prognostic value of different noninvasive reflex tests on days 4-11 of myocardial infarction. The age varied from 34 to 75 years, 68% were men, and 93.6% were on beta-blockers, all without heart failure NYHA IV on the day of tests. HF power < 65 ms2 during active standing (OR 28.8, 95% CI 4.1-104.2; p = 0.001, positive predictive value 29.4%) was an independent predictor of sudden cardiac death.
In a meta-analytic study carried out in 2021 by Heimrich et al. [17], the objective was to verify whether the analysis of heart rate variability could indicate decreased parasympathetic tone in patients with Parkinson’s disease. A total of 47 studies were evaluated, including 2772 individuals, 1566 of which had Parkinson’s Disease (65.0 ± 0.6 years) and 1206 were healthy controls (62.6 ± 1.0 years). Based on 24 studies, it was possible to detect that the FH ms2 was significantly lower in the group of patients with the disease (145.2 ± 41.1 versus 219.4 ± 48.8 ms2; P = 0.002; heterogeneity 91%).
5. Objective
Considering that the heart rate (HR), the root-mean-square of successive differences between adjacent normal RR intervals (RMSSD) and the HF band power in the frequency range between 0.15 and 0.4 Hz (HFms2), can help to differentiate the homeostatic level between individuals with severe impairment and high risk, and healthy individuals, we performed an intensive review of the literature by collecting published data involving the aforementioned variables, in search of a cutoff value for defining homeostatic reference levels and creating an individualized diagnostic coding.
6. Method
Based on research projects linked to FAPESP - Brazil (2017/12529-7) and CNPq -Brazil (308,555/2018-0), studies involving the use of one or more of the three variables mentioned above were evaluated. In total, it was possible to analyze 164 studies involving the heart rate of individuals with importantly compromised homeostatic level (HL_ic), 181 studies involving the heart rate of apparently healthy individuals (HL_ah), 179 studies involving the RMSSD of individuals with HL_ic, 221 studies involving the RMSSD from HL_ah subjects, 125 studies involving the HF ms2 of subjects with HL_ic and 155 studies involving the HF ms2 of HL_ah subjects. Obviously, there were concurrent studies in certain situations. Due to a large number of references, they are cited separately and available in a supplementary file.
7. Statistical analysis
Data were presented as mean and standard deviation, weighted mean, quantities, percentages and correlation coefficients. Comparisons between groups were made by analysis of variance or the Kruskal-Wallis test and its post-tests, according to the indication. Correlation graphs were constructed and Box-Whisker graphs were used for illustration. An alpha error of 5% was accepted, with P values less than or equal to 0.05 being considered significant. The statistical software used was StatsDirect version 3.3.5 (03/22/2021).
8. Results
The total amount of data analyzed was extremely high. Table 1 below indicates the amounts for each variable under conditions of significantly compromised and apparently healthy homeostasis, as well as the mean and standard deviation values for the age of the group, the mean and standard deviation of the variable, and the weighted mean of the variable.
N References
N Data
Age [Mean ± SD]
Variable [Mean ± SD]
Variable [weighted mean]
P-value
HR HL_ic bpm
164
365,195
48.7 ± 20.7
97.6 ± 20.1
85.7
HR HL_ah bpm
181
22,443
32.9 ± 21.7
75.9 ± 18.9
69.7
P < 0.0001
RMSSD HL_ic ms
179
10,014
54.4 ± 16.5
22.8 ± 19.9
27.4
RMSSD HL_ah ms
221
35,531
30.1 ± 19.3
45.6 ± 18.8
32.5
P < 0.0001
HF ms2 HL_ic ms2
125
6830
54.2 ± 15.2
173.7 ± 181.4
155.9
HF ms2 HL_ah ms2
155
25,953
32.7 ± 19.7
565.2 ± 459.1
468.1
P < 0.0001
Table 1.
Distribution of the number of studies included, amount of data per variable, according to homeostatic level (importantly compromised [HL_ic] or apparently healthy [HL_ah].
As the behavior of heart rate variability is related to age, linear correlation calculations were made between age (predictor) and the variable to be predicted (HR, RMSSD or HFms2) in the HL_ic and HL_ah groups (Table 2; Figures 1–6).
Distribution of simple linear regression, correlation coefficients (r and r2) and two-sided P-values, by homeostatic condition.
Correlation coefficient is not significantly different from zero.
Figure 1.
Correlation graphs (age x heart rate) in the groups of individuals with importantly compromised homeostatic level (HL-ic) and apparently healthy (HL_ah).
Figure 2.
Correlation graphs (age x RMSSD) in the groups of individuals with importantly compromised homeostatic level (HL-ic) and apparently healthy (HL_ah).
Figure 3.
Correlation graphs (age x HF ms2) in the groups of individuals with importantly compromised homeostatic level (HL-ic) and apparently healthy (HL_ah).
Figure 4.
Scattergram (HR in bpm) for the groups of individuals with importantly compromised homeostatic level (HL- ic; red circles) and apparently healthy (HL_ah; blue squares).
Figure 5.
Scattergram (RMSSD in ms) for the groups of individuals with importantly compromised homeostatic level (HL- ic; red circles) and apparently healthy (HL_ah; blue squares).
Figure 6.
Scattergram (HF in ms2) for the groups of individuals with importantly compromised homeostatic level (HL- ic; red circles) and apparently healthy (HL_ah; blue squares).
A moderate negative correlation was found between heart rate and age, both in cases with significant homeostatic impairment and in apparently healthy cases. There was also a moderate negative correlation between RMSSD and age, and between HFms2 and age in the apparently healthy group. The fact that there was only a weak negative correlation between HFms2 and age in the group with significant homeostatic impairment and also the absence of correlation between RMSSD and age in this impaired group, was noteworthy. This may suggest that RMSSD is a more effective or sensitive biological marker of homeostasis, revealing changes regardless of age.
It became also relevant to evaluate the data of the three selected variables, in the group composed of individuals named as being from the general population (HL_gp). Thus, from the global data survey carried out, a number of 10,121,910 were obtained from individuals from the general population, in different age groups. The values of mean, standard deviation, weighted mean, mean age ± standard deviation and number of articles consulted are found in Table 3 and Figure 7.
Heart rate
RMSSD
HF ms2
Data (N)
144,817
5,098,117
4,878,976
Mean
71.1
30.3
273.1
Standard Deviation
5.8
12.5
266.2
Weighted mean
68.3
43.2
569.2
Age (mean ± SD)
51.0 ± 15.3
48.9 ± 16.8
50.9 ± 13.8
References
110
138
118
Table 3.
Data and values were obtained in the assessment of the general population (HL_gp).
Figure 7.
Box-whisker graphs of the distributions of values for heart rate (A), RMSSD (B) and HF ms2 (C) variables, by the homeostatic level group.
Comparative statistical analysis between the 3 groups (HL_ah, HL_ic and HL_gp) for the three selected variables, using the Kruskal-Wallis test with post-test Dwass-Steel-Chritchlow-Fligner, showed a non-significant difference between HR HL_ah versus HR HL_gp (P = 0.6228); the statistically significant difference between HR HL_ah versus HR HL_ic (P < 0.0001); the statistically significant difference between HR HL_gp versus HR HL_ic (P < 0.0001).
Regarding the variable RMSSD, there was a statistically significant difference between RMSSD HL_ah versus RMSSD HL_gp (P < 0.0001); the statistically significant difference between RMSSD HL_ah versus RMSSD HL_ic (P < 0.0001); the statistically significant difference between RMSSD HL_gp versus RMSSD HL_ic (P < 0.0001).
In the comparative analysis of the variable HF ms2, there was a statistically significant difference between RMSSD HL_ah versus RMSSD HL_gp (P < 0.0001); statistically significant difference between RMSSD HL_ah versus RMSSD HL_ic (P < 0.0001); statistically significant difference between RMSSD HL_gp versus RMSSD HL_ic (P = 0.0002).
Therefore, it is concluded that data from the so-called general population are not suitable to be considered as a normal condition and this must be taken into account when this group is used as a control group.
Finally, based on the weighted average of the results in Table 1, on the scatter plots involving the group of individuals with significant homeostatic impairment and the group of apparently healthy individuals, we propose a classification model for the individual homeostatic level. This classificatory model is a three-level, three-stage alphanumeric coding, designed as follows:
Level A: Heart Rate (bpm)
Stage A1: Heart Rate less than 70 bpm
Stage A2: Heart Rate between 70 and 85 bpm
Stage A3: Heart Rate above 85 bpm
Level B: RMSSD (ms)
Stage B1: RMSSD above 32 milliseconds.
Stage B2: RMSSD between 32 and 28 milliseconds.
Stage B3: RMSSD less than 28 milliseconds.
Level C: HF ms2
Stage C1: HF ms2 above 468 ms2
Stage C2: HF ms2 between 468 and 156 ms2.
Stage C3: HF ms2 less than 156 ms2.
Thus, a totally healthy individual, with an excellent Homeostatic Level and, therefore, with very low risk, would receive the A1B1C1 classification. An individual with a high basal heart rate, a very low RMSSD value and a very low HF power value would be classified as A3B3C3 indicating high severity, low homeostatic level and, therefore, at high risk. Several intermediate combinations would be possible characterizing the current state of each case. The figure below illustrates the full set of possibilities (Figure 8).
Figure 8.
Set of possibilities in the alphanumeric classification of the individual homeostatic level (Created by the authors).
In conclusion, the present analytical study, based on an extensive amount of data published in the literature (more than 10.5 million values), referring to three recognized variables of heart rate variability markers of the level of homeostasis, allowed us to define cut-off levels indicative of apparently healthy or with important homeostatic compromise. It was possible to conclude that values obtained in the general population are not equivalent to normal values, a fact that must be considered when this group is used as a control. It was also possible, to elaborate a very simple alphanumeric classification with practical applicability in the characterization of the individual homeostatic level.
\n',keywords:"autonomic nervous system, heart rate variability, homeostatic level",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80895.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80895.xml",downloadPdfUrl:"/chapter/pdf-download/80895",previewPdfUrl:"/chapter/pdf-preview/80895",totalDownloads:36,totalViews:0,totalCrossrefCites:0,dateSubmitted:"January 3rd 2022",dateReviewed:"January 5th 2022",datePrePublished:"March 20th 2022",datePublished:null,dateFinished:"March 20th 2022",readingETA:"0",abstract:"Many variables have been used as homeostatic level markers. Heart Rate Variability (HRV) has been frequently cited as an indicator of homeostatic status. Low levels of HRV are associated with aging, disease, or increased risk of death. We present a study based on more than 10.5 million data collected from the literature, associating the degree of global clinical impairment of individuals, with their respective HRV data, seeking to establish a classification of Homeostatic Levels. Three specific variables were evaluated: heart rate (HR), the root-mean-square of successive differences between adjacent normal RR intervals in a time interval (RMSSD) and the HF band (HF ms2). It was possible to detect significant differences between the 83,927 data from healthy individuals and the 382,039 data from individuals with significant homeostatic impairment. It was demonstrated that the RMSSD is very sensitive to the worst homeostatic state, presenting a behavior independent of age and that the values found in the general population do not match the values of apparently healthy individuals. An alphanumeric classification of the homeostatic level in a three-level architecture was proposed, with three stages for each level, which may be extremely useful in prognostic assessment and decision-making about individual people.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80895",risUrl:"/chapter/ris/80895",signatures:"Moacir Fernandes de Godoy and Michele Lima Gregório",book:{id:"10835",type:"book",title:"Autonomic Nervous System - Special Interest Topics",subtitle:null,fullTitle:"Autonomic Nervous System - Special Interest Topics",slug:null,publishedDate:null,bookSignature:"Dr. Theodoros Aslanidis and M.Sc. Christos Nouris",coverURL:"https://cdn.intechopen.com/books/images_new/10835.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-193-7",printIsbn:"978-1-80355-192-0",pdfIsbn:"978-1-80355-194-4",isAvailableForWebshopOrdering:!0,editors:[{id:"200252",title:"Dr.",name:"Theodoros",middleName:null,surname:"Aslanidis",slug:"theodoros-aslanidis",fullName:"Theodoros Aslanidis"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"305849",title:"Dr.",name:"Moacir",middleName:"Fernandes",surname:"Godoy",fullName:"Moacir Godoy",slug:"moacir-godoy",email:"mf60204@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"305851",title:"Dr.",name:"Michele",middleName:null,surname:"Gregório",fullName:"Michele Gregório",slug:"michele-gregorio",email:"michele.mirassol@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Heart rate",level:"1"},{id:"sec_3",title:"3. RMSSD",level:"1"},{id:"sec_4",title:"4. HF ms2",level:"1"},{id:"sec_5",title:"5. Objective",level:"1"},{id:"sec_6",title:"6. Method",level:"1"},{id:"sec_7",title:"7. Statistical analysis",level:"1"},{id:"sec_8",title:"8. Results",level:"1"}],chapterReferences:[{id:"B1",body:'Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, et al. An estimation of the number of cells in the human body. Annals of Human Biology. 2013;40(6):463-471. DOI: 10.3109/03014460.2013.807878 Epub 2013 Jul 5. Erratum in: Ann Hum Biol. 2013 Nov-Dec;40(6):471'},{id:"B2",body:'Deutekom AW. The origins of children’s Energy balance-related behavior and physical fitness (thesis). Amsterdam, Netherlands: Vrije Universiteit; 2017'},{id:"B3",body:'Kuchel GA, Hof PR. Autonomic nervous system in old age. Basel: Karger; 2004'},{id:"B4",body:'Vanderlei LC, Pastre CM, Hoshi RA, Carvalho TD, Godoy MF. 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DOI: 10.1016/j.jjcc.2013.02.018'},{id:"B9",body:'Maurer CW, Liu VD, LaFaver K, Ameli R, Wu T. Impaired resting vagal tone in patients with functional movement disorders. Parkinsonism & Related Disorders. 2016;30:18-22. DOI: 10.1016/j.parkreldis. 2016.06.009'},{id:"B10",body:'DeGiorgio CM, Miller P, Meymandi S, Chin A, Epps J, Gordon S, et al. RMSSD, a measure of vagus-mediated heart rate variability, is associated with risk factors for SUDEP: the SUDEP-7 Inventory. Epilepsy & Behavior. 2010;19(1):78-81. DOI: 10.1016/j.yebeh.2010.06.011), 10.1016/j.yebeh.2010.06.011)'},{id:"B11",body:'Maheshwari A, Norby FL, Soliman EZ, Adabag S, Whitsel EA, Alonso A, et al. Low heart rate variability in a 2-minute electrocardiogram recording is associated with na increased risk of sudden cardiac death in the general population: the atherosclerosis risk in communities study. PLoS One. 2016, 2016;11(8):e0161648. DOI: 10.1371/journal.pone.0161648'},{id:"B12",body:'Bonjorno Junior JC, Caruso FR, Mendes RG, da Silva TR, Biazon TMPC, Rangel F, et al. Noninvasive measurements of hemodynamic, autonomic and endothelial function as predictors of mortality in sepsis: A prospective cohort study. PLoS One. 2019;14(3):e0213239. DOI: 10.1371/journal.pone 0213239. Erratum in: PLoS One. 2019 Apr 30;14(4):e0216505'},{id:"B13",body:'Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation. 1996;93(5):1043-1065'},{id:"B14",body:'Lee TB, Nicolaas C, Piet B, Margaretha V. Validity of commonly used heart rate variability markers of autonomic nervous system function. Neuropsychobiology. 2019;8(1):1-13. DOI: 10.1159/000495519'},{id:"B15",body:'Doheny KK, Palmer C, Browning KN, Jairath P, Liao D, He F, et al. Diminished vagal tone is a predictive biomarker of necrotizing enterocolitis-risk in preterm infants. Neurogastroenterology and Motility. 2014;26:832-840. DOI: 10.1111/nmo.12337'},{id:"B16",body:'Abramkin DV, Iavelov IS, Gratsianskiĭ NA. Neinvazivnye serdechno-sosudistye reflektornye testy i prognoz vnezapnoĭ serdechnoĭ smerti posle perenesennogo infarkta miokarda: kakoĭ metod predpochest\'? [Simple cardiovascular reflex tests in prediction of sudden death after myocardial infarction: Which method to prefer?]. Kardiologiia. 2004;44(10):4-12 Russian'},{id:"B17",body:'Heimrich KG, Lehmann T, Schlattmann P, Prell T. Heart rate variability analyses in parkinson’s disease: A systematic review and meta-analysis. Brain Sciences. 2021;11:959. DOI: 10.3390/brainsci11080959'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Moacir Fernandes de Godoy",address:"mf60204@gmail.com",affiliation:'
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Kimatu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10686",title:"Natural Gas",subtitle:"New Perspectives and Future Developments",isOpenForSubmission:!1,hash:"581763788a6a59e653a9d1d9b5a42d79",slug:"natural-gas-new-perspectives-and-future-developments",bookSignature:"Maryam Takht Ravanchi",coverURL:"https://cdn.intechopen.com/books/images_new/10686.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"2416",title:"Dr.",name:"Maryam",middleName:null,surname:"Takht Ravanchi",slug:"maryam-takht-ravanchi",fullName:"Maryam Takht Ravanchi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10988",title:"Railway Transport Planning and Manageme",subtitle:null,isOpenForSubmission:!1,hash:"5cb54cc53caedad9ec78372563c82e2c",slug:"railway-transport-planning-and-management",bookSignature:"Stefano de Luca, Roberta Di Pace and Chiara Fiori",coverURL:"https://cdn.intechopen.com/books/images_new/10988.jpg",editedByType:"Edited by",publishedDate:"June 28th 2022",editors:[{id:"271061",title:"Prof.",name:"Stefano",middleName:null,surname:"de Luca",slug:"stefano-de-luca",fullName:"Stefano de Luca"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1076",title:"Chronooncology",slug:"chronooncology",parent:{id:"190",title:"Oncology",slug:"medicine-oncology"},numberOfBooks:2,numberOfSeries:0,numberOfAuthorsAndEditors:71,numberOfWosCitations:35,numberOfCrossrefCitations:23,numberOfDimensionsCitations:56,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"1076",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"5730",title:"Unique Aspects of Anti-cancer Drug Development",subtitle:null,isOpenForSubmission:!1,hash:"9cdd2d8e095ad4f83da2b26cb3e239c7",slug:"unique-aspects-of-anti-cancer-drug-development",bookSignature:"Jolanta Natalia Latosinska and Magdalena Latosinska",coverURL:"https://cdn.intechopen.com/books/images_new/5730.jpg",editedByType:"Edited by",editors:[{id:"77808",title:"Dr.",name:"Jolanta Natalia",middleName:null,surname:"Latosińska",slug:"jolanta-natalia-latosinska",fullName:"Jolanta Natalia Latosińska"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5767",title:"Natural Products and Cancer Drug Discovery",subtitle:null,isOpenForSubmission:!1,hash:"6d12d5b2fe98bfc2a6411f1b26d8f028",slug:"natural-products-and-cancer-drug-discovery",bookSignature:"Farid A. Badria",coverURL:"https://cdn.intechopen.com/books/images_new/5767.jpg",editedByType:"Edited by",editors:[{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:2,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"54517",doi:"10.5772/67573",title:"Flavonoids: Promising Natural Products for Treatment of Skin Cancer (Melanoma)",slug:"flavonoids-promising-natural-products-for-treatment-of-skin-cancer-melanoma-",totalDownloads:1941,totalCrossrefCites:4,totalDimensionsCites:13,abstract:"Melanoma, which is the most malignant skin cancer type, has got one of the fastest increasing incidence rates of all cancer types in the world. When belatedly diagnosed, melanoma is extremely invasive and metastatic. Although there are effective drugs used to treat melanoma, some cell lines have proven resistant to chemotherapy. In this context, several research groups on natural products have investigated the anticancer effect of new natural molecules in the treatment of melanoma. Flavonoids have shown to play an important role in chemoprevention and inhibition of the proliferation, migration, and invasion of melanoma cells. In this chapter, we present a systematic review performed through a literature search over a period of 20 years, using specialized databases. Analysis of all selected manuscripts demonstrated that at least 97 flavonoids have already been investigated for the treatment of melanoma using in vitro or in vivo models. Most of the bioactive flavonoids belong to the classes of flavones (38.0%), flavonols (17.5%), or isoflavonoids (17.5%). Apigenin, diosmin, fisetin, luteolin, and quercetin were considered as the most studied flavonoids for melanoma treatment. In general, flavonoids have shown to be a promising source of molecules with great potential for the treatment of melanoma.",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Raimundo Gonçalves de Oliveira Júnior, Christiane Adrielly Alves\nFerraz, Mariana Gama e Silva, Érica Martins de Lavor, Larissa Araújo\nRolim, Julianeli Tolentino de Lima, Audrey Fleury, Laurent Picot,\nJullyana de Souza Siqueira Quintans, Lucindo José Quintans Júnior\nand Jackson Roberto Guedes da Silva Almeida",authors:[{id:"70159",title:"Dr.",name:"Lucindo",middleName:null,surname:"Quintans-Júnior",slug:"lucindo-quintans-junior",fullName:"Lucindo Quintans-Júnior"},{id:"72113",title:"Prof.",name:"Jackson",middleName:"Roberto Guedes Da Silva",surname:"Almeida",slug:"jackson-almeida",fullName:"Jackson Almeida"},{id:"203273",title:"Dr.",name:"Jullyana",middleName:null,surname:"de Souza Siqueira Quintans",slug:"jullyana-de-souza-siqueira-quintans",fullName:"Jullyana de Souza Siqueira Quintans"},{id:"203426",title:"Dr.",name:"Laurent",middleName:null,surname:"Picot",slug:"laurent-picot",fullName:"Laurent Picot"},{id:"204628",title:"Mr.",name:"Raimundo",middleName:null,surname:"Oliveira-Junior",slug:"raimundo-oliveira-junior",fullName:"Raimundo Oliveira-Junior"},{id:"204629",title:"MSc.",name:"Christiane",middleName:null,surname:"Ferraz",slug:"christiane-ferraz",fullName:"Christiane Ferraz"},{id:"204630",title:"MSc.",name:"Mariana",middleName:null,surname:"Silva",slug:"mariana-silva",fullName:"Mariana Silva"},{id:"204631",title:"Ms.",name:"Erica",middleName:null,surname:"Lavor",slug:"erica-lavor",fullName:"Erica Lavor"},{id:"204632",title:"Prof.",name:"Julianeli",middleName:null,surname:"Lima",slug:"julianeli-lima",fullName:"Julianeli Lima"},{id:"204633",title:"Prof.",name:"Larissa",middleName:null,surname:"Rolim",slug:"larissa-rolim",fullName:"Larissa Rolim"},{id:"204634",title:"Prof.",name:"Audrey",middleName:null,surname:"Fleury",slug:"audrey-fleury",fullName:"Audrey Fleury"}]},{id:"55925",doi:"10.5772/67797",title:"Endophytic Fungi as Alternative and Reliable Sources for Potent Anticancer Agents",slug:"endophytic-fungi-as-alternative-and-reliable-sources-for-potent-anticancer-agents",totalDownloads:2e3,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"In comparison with other natural sources like plants, highly diverse microorganisms are narrowly explored, especially with respect to their limitless potentials as repositories of exceptionally bioactive natural products. Of these organisms, fungi inhabiting tissues of plant in a noninvasive relationship (endophytic fungi) have proven undeniably useful and unmatchable as sources of potent bioactive molecules against several diseases such as cancer and related ailments. In general terms, endophytic fungi are highly prevalent organisms found in the tissue (intracellular or intercellular) of plants and at least for reasonable portion of their lives. It has been proven that virtually every plant, irrespective of habitat and climate, plays host to wide varieties of endophytes. Endophytic fungi produce metabolites produced by different biosynthetic pathways to that of the host plant, and this robustness equips them to synthesize unlimited structural entities and scaffolds of diverse classes. Interestingly too, the cohabitation/culture of these fungi with certain bacteria offers even stronger hopes for anticancer drug discovery. The endless need for potent drugs has necessitated the search of bioactive molecules from several sources, and endophytic fungi appear to be a recipe. This chapter is an attempt to present the current trend of research with these very promising organisms.",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Edwin O. Omeje, Joy E. Ahomafor, Theophilus U. Onyekaba, Philip\nO. Monioro, Ibekwe Nneka, Sunday Onyeloni, Charles Chime and\nJonathan C. Eboka",authors:[{id:"197824",title:"Dr.",name:"Edwin",middleName:"Ogechukwu",surname:"Omeje",slug:"edwin-omeje",fullName:"Edwin Omeje"},{id:"198038",title:"Dr.",name:"Nneka",middleName:null,surname:"Ibekwe",slug:"nneka-ibekwe",fullName:"Nneka Ibekwe"},{id:"198039",title:"MSc.",name:"Joy",middleName:null,surname:"Ahomafor",slug:"joy-ahomafor",fullName:"Joy Ahomafor"},{id:"198040",title:"Mr.",name:"Sunday",middleName:null,surname:"Onyeloni",slug:"sunday-onyeloni",fullName:"Sunday Onyeloni"},{id:"198041",title:"Mr.",name:"Philip",middleName:null,surname:"Monioro",slug:"philip-monioro",fullName:"Philip Monioro"},{id:"204822",title:"Dr.",name:"Charles",middleName:null,surname:"Chime",slug:"charles-chime",fullName:"Charles Chime"}]},{id:"54388",doi:"10.5772/67650",title:"Computational Studies and Biosynthesis of Natural Products with Promising Anticancer Properties",slug:"computational-studies-and-biosynthesis-of-natural-products-with-promising-anticancer-properties",totalDownloads:1951,totalCrossrefCites:5,totalDimensionsCites:6,abstract:"We present an overview of computational approaches for the prediction of metabolic pathways by which plants biosynthesise compounds, with a focus on selected very promising anticancer secondary metabolites from floral sources. We also provide an overview of databases for the retrieval of useful genomic data, discussing the strengths and limitations of selected prediction software and the main computational tools (and methods), which could be employed for the investigation of the uncharted routes towards the biosynthesis of some of the identified anticancer metabolites from plant sources, eventually using specific examples to address some knowledge gaps when using these approaches.",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Aurélien F.A. Moumbock, Conrad V. Simoben, Ludger Wessjohann,\nWolfgang Sippl, Stefan Günther and Fidele Ntie‐Kang",authors:[{id:"177615",title:"Prof.",name:"Ludger",middleName:null,surname:"Aloisius Wessjohann",slug:"ludger-aloisius-wessjohann",fullName:"Ludger Aloisius Wessjohann"},{id:"197160",title:"Dr.",name:"Fidele",middleName:null,surname:"Ntie-Kang",slug:"fidele-ntie-kang",fullName:"Fidele Ntie-Kang"},{id:"197406",title:"Mr.",name:"Conrad Veranso",middleName:null,surname:"Simoben",slug:"conrad-veranso-simoben",fullName:"Conrad Veranso Simoben"},{id:"197408",title:"Prof.",name:"Wolfgang",middleName:null,surname:"Sippl",slug:"wolfgang-sippl",fullName:"Wolfgang Sippl"},{id:"199056",title:"Mr.",name:"Aurelien F. A.",middleName:null,surname:"Moumbock",slug:"aurelien-f.-a.-moumbock",fullName:"Aurelien F. A. Moumbock"},{id:"199057",title:"Prof.",name:"Stefan",middleName:null,surname:"Günther",slug:"stefan-gunther",fullName:"Stefan Günther"}]},{id:"54745",doi:"10.5772/68131",title:"Lycopene: Multitargeted Applications in Cancer Therapy",slug:"lycopene-multitargeted-applications-in-cancer-therapy",totalDownloads:1880,totalCrossrefCites:2,totalDimensionsCites:6,abstract:"Cancer is an uncontrolled growth and division of cells, leading to significant morbidity and mortality and economic burden to the society. Natural products as anticancer molecules have drawn the attention of researchers and have resulted in the development of many successful anticancer drugs, which include camptothecins, epipodophyllotoxins, vinca alkaloids, and taxanes. Another group of compounds with anti-cancer effects include botanicals (phytochemicals) found in the diet. In recent years, a tomato carotenoid lycopene (LYC) has gained attention for its potential health benefits, especially in prevention and treatment of cancer. The studies suggest that the consumption LYC in food or by itself may reduce cancer risk. However, there are insufficient clinical trial data to support the hypothesis. LYC may play a preventive role in a variety of cancers, especially in prostate cancer. It acts by multiple mechanisms including the regulation of growth factor signalling, cell cycle arrest and/or apoptosis induction, metastasis and angiogenesis, as well as by modulating the anti-inflammatory and phase II detoxification enzymes activities. The effects can be attributed to the unique chemical structure of the carotenoid which confers it a strong antioxidant property. In this chapter, we discuss the chemopreventive and anti-cancer properties of LYC, a dietary carotenoid.”",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Kazim Sahin, Shakir Ali, Nurhan Sahin, Cemal Orhan and Omer\nKucuk",authors:[{id:"39589",title:"Prof.",name:"Kazim",middleName:null,surname:"Sahin",slug:"kazim-sahin",fullName:"Kazim Sahin"}]},{id:"55790",doi:"10.5772/intechopen.68506",title:"Phytocompounds Targeting Cancer Angiogenesis Using the Chorioallantoic Membrane Assay",slug:"phytocompounds-targeting-cancer-angiogenesis-using-the-chorioallantoic-membrane-assay",totalDownloads:1816,totalCrossrefCites:2,totalDimensionsCites:6,abstract:"Cancer is the second cause of mortality worldwide. Angiogenesis is an important process involved in the growth of primary tumors and metastasis. New approaches for controlling the cancer progression and invasiveness can be addressed by limiting the angiogenesis process. An increasingly large number of natural compounds are evaluated as angiogenesis inhibitors. The chorioallantoic membrane (CAM) assay represents an in vivo attractive experimental model for cancer and angiogenesis studies as prescreening to the murine models. Since the discovery of tumor angiogenesis, the CAM has been intensively used in cancer research. The advantages of this in vivo technique are in terms of low time-consuming, costs, and a lower number of sacrificed animals. Currently, a great number of natural compounds are being investigated for their effectiveness in controlling tumor angiogenesis. Potential reducing of angiogenesis has been investigated by our group for pentacyclic triterpenes, in various formulations, and differences in their mechanism were registered. This chapter aims to give an overview on a number of phytocompounds investigated using in vitro, murine models and the chorioallantoic membrane assay as well as to emphasize the use of CAM assay in the study of natural compounds with potential effects in malignancies.",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Stefana Avram, Roxana Ghiulai, Ioana Zinuca Pavel, Marius Mioc,\nRoxana Babuta, Mirela Voicu, Dorina Coricovac, Corina Danciu,\nCristina Dehelean and Codruta Soica",authors:[{id:"141027",title:"Dr.",name:"Cristina",middleName:null,surname:"Dehelean",slug:"cristina-dehelean",fullName:"Cristina Dehelean"},{id:"173283",title:"Dr.",name:"Dorina",middleName:null,surname:"Coricovac",slug:"dorina-coricovac",fullName:"Dorina Coricovac"},{id:"186372",title:"Prof.",name:"Corina",middleName:null,surname:"Danciu",slug:"corina-danciu",fullName:"Corina Danciu"},{id:"186680",title:"Dr.",name:"Roxana",middleName:null,surname:"Ghiulai",slug:"roxana-ghiulai",fullName:"Roxana Ghiulai"},{id:"197894",title:"Prof.",name:"Codruta",middleName:null,surname:"Soica",slug:"codruta-soica",fullName:"Codruta Soica"},{id:"197929",title:"Dr.",name:"Stefana",middleName:null,surname:"Avram",slug:"stefana-avram",fullName:"Stefana Avram"},{id:"202529",title:"Dr.",name:"Ioana Zinuca",middleName:null,surname:"Pavel",slug:"ioana-zinuca-pavel",fullName:"Ioana Zinuca Pavel"},{id:"205584",title:"Mr.",name:"Marius",middleName:null,surname:"Mioc",slug:"marius-mioc",fullName:"Marius Mioc"},{id:"205585",title:"Dr.",name:"Roxana",middleName:null,surname:"Racoviceanu (Babuta)",slug:"roxana-racoviceanu-(babuta)",fullName:"Roxana Racoviceanu (Babuta)"},{id:"205586",title:"Ms.",name:"Mirela",middleName:null,surname:"Voicu",slug:"mirela-voicu",fullName:"Mirela Voicu"}]}],mostDownloadedChaptersLast30Days:[{id:"54281",title:"Towards Metabolic Engineering of Podophyllotoxin Production",slug:"towards-metabolic-engineering-of-podophyllotoxin-production",totalDownloads:1693,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"The pharmaceutically important anticancer drugs etoposide and teniposide are derived from podophyllotoxin, a natural product isolated from roots of Podophyllum hexandrum growing in the wild. The overexploitation of this endangered plant has led to the search for alternative sources. Metabolic engineering aimed at constructing the pathway in another host cell is very appealing, but for that approach, an in-depth knowledge of the pathway toward podophyllotoxin is necessary. In this chapter, we give an overview of the lignan pathway leading to podophyllotoxin. Subsequently, we will discuss the engineering possibilities to produce podophyllotoxin in a heterologous host. This will require detailed knowledge on the cellular localization of the enzymes of the lignan biosynthesis pathway. Due to the high number of enzymes involved and the scarce information on compartmentalization, the heterologous production of podophyllotoxin still remains a tremendous challenge. At the moment, research is focusing on the last step(s) in the conversion of deoxypodophyllotoxin to (epi)podophyllotoxin and 4′-demethyldesoxypodophyllotoxin by plant cytochromes.",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Christel L. C. Seegers, Rita Setroikromo and Wim J. Quax",authors:[{id:"196901",title:"Prof.",name:"Wim",middleName:null,surname:"Quax",slug:"wim-quax",fullName:"Wim Quax"},{id:"197867",title:"MSc.",name:"Christel L.C.",middleName:null,surname:"Seegers",slug:"christel-l.c.-seegers",fullName:"Christel L.C. Seegers"},{id:"197868",title:"Ms.",name:"Rita",middleName:null,surname:"Setroikromo",slug:"rita-setroikromo",fullName:"Rita Setroikromo"}]},{id:"55831",title:"African Plants with Antiproliferative Properties",slug:"african-plants-with-antiproliferative-properties",totalDownloads:2091,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Plant-derived compounds have been an integral component in man’s quest to discover ideal anticancer agents. A number of new agents are currently in clinical development with promising selective activity against cancer cell lines and cancer-related molecular targets. This book chapter discusses 14 of such compounds isolated from African plants from 15 plant families. Also contained in this book chapter are compounds from African plants that hold prospect as potential anticancer agents as informed by their in vitro and in vivo preclinical studies. It is, therefore, worthwhile that researchers in the African continent and the world over should keep on working on identifying biomolecules with potential in cancer management.",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Newman Osafo, Yaw Duah Boakye, Christian Agyare, Samuel\nObeng, Judith Edem Foli and Prince Amankwaah Baffour Minkah",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"186987",title:"Dr.",name:"Yaw Duah",middleName:null,surname:"Boakye",slug:"yaw-duah-boakye",fullName:"Yaw Duah Boakye"},{id:"196452",title:"Dr.",name:"Newman",middleName:null,surname:"Osafo",slug:"newman-osafo",fullName:"Newman Osafo"},{id:"201381",title:"Ms.",name:"Judith",middleName:null,surname:"Edem Foli",slug:"judith-edem-foli",fullName:"Judith Edem Foli"},{id:"201382",title:"Mr.",name:"Prince",middleName:"Amankwah Baffour",surname:"Minkah",slug:"prince-minkah",fullName:"Prince Minkah"},{id:"204731",title:"Mr.",name:"Samuel",middleName:null,surname:"Obeng",slug:"samuel-obeng",fullName:"Samuel Obeng"}]},{id:"54388",title:"Computational Studies and Biosynthesis of Natural Products with Promising Anticancer Properties",slug:"computational-studies-and-biosynthesis-of-natural-products-with-promising-anticancer-properties",totalDownloads:1949,totalCrossrefCites:5,totalDimensionsCites:6,abstract:"We present an overview of computational approaches for the prediction of metabolic pathways by which plants biosynthesise compounds, with a focus on selected very promising anticancer secondary metabolites from floral sources. We also provide an overview of databases for the retrieval of useful genomic data, discussing the strengths and limitations of selected prediction software and the main computational tools (and methods), which could be employed for the investigation of the uncharted routes towards the biosynthesis of some of the identified anticancer metabolites from plant sources, eventually using specific examples to address some knowledge gaps when using these approaches.",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Aurélien F.A. Moumbock, Conrad V. Simoben, Ludger Wessjohann,\nWolfgang Sippl, Stefan Günther and Fidele Ntie‐Kang",authors:[{id:"177615",title:"Prof.",name:"Ludger",middleName:null,surname:"Aloisius Wessjohann",slug:"ludger-aloisius-wessjohann",fullName:"Ludger Aloisius Wessjohann"},{id:"197160",title:"Dr.",name:"Fidele",middleName:null,surname:"Ntie-Kang",slug:"fidele-ntie-kang",fullName:"Fidele Ntie-Kang"},{id:"197406",title:"Mr.",name:"Conrad Veranso",middleName:null,surname:"Simoben",slug:"conrad-veranso-simoben",fullName:"Conrad Veranso Simoben"},{id:"197408",title:"Prof.",name:"Wolfgang",middleName:null,surname:"Sippl",slug:"wolfgang-sippl",fullName:"Wolfgang Sippl"},{id:"199056",title:"Mr.",name:"Aurelien F. A.",middleName:null,surname:"Moumbock",slug:"aurelien-f.-a.-moumbock",fullName:"Aurelien F. A. Moumbock"},{id:"199057",title:"Prof.",name:"Stefan",middleName:null,surname:"Günther",slug:"stefan-gunther",fullName:"Stefan Günther"}]},{id:"55922",title:"Lupan-Skeleton Pentacyclic Triterpenes with Activity against Skin Cancer: Preclinical Trials Evolution",slug:"lupan-skeleton-pentacyclic-triterpenes-with-activity-against-skin-cancer-preclinical-trials-evolutio",totalDownloads:1797,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"Skin cancer is an increasingly frequent pathology, with a dangerous high percentage of malignant melanoma. The use of synthetic chemotherapy raises the problem of severe adverse effects and the development of resistance to treatment. Therefore, the use of natural therapies became the focus of numerous research groups due to their high efficacy and lower systemic adverse effects. Among natural products evaluated as therapeutical agents against skin cancer, betulinic acid was emphasized as a highly selective anti-melanoma agent and is currently undergoing phase II clinical trials as topical application. Several other pentacyclic triterpenes exhibit antiproliferative activities. This chapter aims to present the latest main discoveries in the class of pentacyclic triterenes with antitumor effect and the evolution of their preclinical trials. Furthermore, it includes reports on plant sources containing pentacyclic triterpenes, as well as the main possibilities of their water solubilization and cancer cell targeting. A review on recent data regarding mechanisms of action at cellular and molecular levels complements information on the outstanding medicinal potential of these compounds.",book:{id:"5730",slug:"unique-aspects-of-anti-cancer-drug-development",title:"Unique Aspects of Anti-cancer Drug Development",fullTitle:"Unique Aspects of Anti-cancer Drug Development"},signatures:"Codruţa Şoica, Diana Antal, Florina Andrica, Roxana Băbuţa, Alina\nMoacă, Florina Ardelean, Roxana Ghiulai, Stefana Avram, Corina\nDanciu, Dorina Coricovac, Cristina Dehelean and Virgil Păunescu",authors:[{id:"141027",title:"Dr.",name:"Cristina",middleName:null,surname:"Dehelean",slug:"cristina-dehelean",fullName:"Cristina Dehelean"},{id:"173283",title:"Dr.",name:"Dorina",middleName:null,surname:"Coricovac",slug:"dorina-coricovac",fullName:"Dorina Coricovac"},{id:"186372",title:"Prof.",name:"Corina",middleName:null,surname:"Danciu",slug:"corina-danciu",fullName:"Corina Danciu"},{id:"186678",title:"Dr.",name:"Codruta",middleName:null,surname:"Soica",slug:"codruta-soica",fullName:"Codruta Soica"},{id:"186679",title:"Dr.",name:"Diana",middleName:null,surname:"Antal",slug:"diana-antal",fullName:"Diana Antal"},{id:"186680",title:"Dr.",name:"Roxana",middleName:null,surname:"Ghiulai",slug:"roxana-ghiulai",fullName:"Roxana Ghiulai"},{id:"202526",title:"Dr.",name:"Stefana",middleName:null,surname:"Avram",slug:"stefana-avram",fullName:"Stefana Avram"},{id:"205282",title:"Dr.",name:"Florina",middleName:null,surname:"Ardelean",slug:"florina-ardelean",fullName:"Florina Ardelean"},{id:"205679",title:"Dr.",name:"Florina",middleName:null,surname:"Andrica",slug:"florina-andrica",fullName:"Florina Andrica"},{id:"205680",title:"Dr.",name:"Roxana",middleName:null,surname:"Racoviceanu (Babuta)",slug:"roxana-racoviceanu-(babuta)",fullName:"Roxana Racoviceanu (Babuta)"},{id:"205681",title:"Dr.",name:"Alina",middleName:null,surname:"Moaca",slug:"alina-moaca",fullName:"Alina Moaca"}]},{id:"55925",title:"Endophytic Fungi as Alternative and Reliable Sources for Potent Anticancer Agents",slug:"endophytic-fungi-as-alternative-and-reliable-sources-for-potent-anticancer-agents",totalDownloads:1999,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"In comparison with other natural sources like plants, highly diverse microorganisms are narrowly explored, especially with respect to their limitless potentials as repositories of exceptionally bioactive natural products. Of these organisms, fungi inhabiting tissues of plant in a noninvasive relationship (endophytic fungi) have proven undeniably useful and unmatchable as sources of potent bioactive molecules against several diseases such as cancer and related ailments. In general terms, endophytic fungi are highly prevalent organisms found in the tissue (intracellular or intercellular) of plants and at least for reasonable portion of their lives. It has been proven that virtually every plant, irrespective of habitat and climate, plays host to wide varieties of endophytes. Endophytic fungi produce metabolites produced by different biosynthetic pathways to that of the host plant, and this robustness equips them to synthesize unlimited structural entities and scaffolds of diverse classes. Interestingly too, the cohabitation/culture of these fungi with certain bacteria offers even stronger hopes for anticancer drug discovery. The endless need for potent drugs has necessitated the search of bioactive molecules from several sources, and endophytic fungi appear to be a recipe. This chapter is an attempt to present the current trend of research with these very promising organisms.",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Edwin O. Omeje, Joy E. Ahomafor, Theophilus U. Onyekaba, Philip\nO. Monioro, Ibekwe Nneka, Sunday Onyeloni, Charles Chime and\nJonathan C. Eboka",authors:[{id:"197824",title:"Dr.",name:"Edwin",middleName:"Ogechukwu",surname:"Omeje",slug:"edwin-omeje",fullName:"Edwin Omeje"},{id:"198038",title:"Dr.",name:"Nneka",middleName:null,surname:"Ibekwe",slug:"nneka-ibekwe",fullName:"Nneka Ibekwe"},{id:"198039",title:"MSc.",name:"Joy",middleName:null,surname:"Ahomafor",slug:"joy-ahomafor",fullName:"Joy Ahomafor"},{id:"198040",title:"Mr.",name:"Sunday",middleName:null,surname:"Onyeloni",slug:"sunday-onyeloni",fullName:"Sunday Onyeloni"},{id:"198041",title:"Mr.",name:"Philip",middleName:null,surname:"Monioro",slug:"philip-monioro",fullName:"Philip Monioro"},{id:"204822",title:"Dr.",name:"Charles",middleName:null,surname:"Chime",slug:"charles-chime",fullName:"Charles Chime"}]}],onlineFirstChaptersFilter:{topicId:"1076",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
\r\n
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
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\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
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\r\n\t
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"June 28th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. Her publications cover a wide range of scientific and technical research publications that include edited books, book chapters, refereed journals, refereed conference papers and reports for local, state and federal government clients. She has also produced podcasts for various organisations and participated in media interviews. She has received state, national and international funding worth over USD $25 million. Usha has been awarded the Quarterly Franklin Membership by London Journals Press (UK). Her biography has been included in the Marquis Who's Who in the World® 2018, 2016 (33rd Edition), along with approximately 55,000 of the most accomplished men and women from around the world, including luminaries as U.N. Secretary-General Ban Ki-moon. In 2017, Usha was awarded the Marquis Who’s Who Lifetime Achiever Award.",institutionString:null,institution:{name:"RMIT University",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,annualVolume:11975,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo is a Professor at the Department of Engineering of the University of Naples “Parthenope”, Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino. Her research interests include multi-criteria decision analysis, industrial plant, logistics, manufacturing and safety. She serves as an Associate Editor for the International Journal of the Analytic Hierarchy Process. She is a member of AHP Academy and a member of several editorial boards. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. 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She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. from Integral University, Lucknow, India, with his work titled ‘Development and evaluation of silymarin nanoformulation for hepatic carcinoma’. Currently, he is an Assistant Professor of Pharmaceutics, at the Faculty of Pharmacy, Integral University. He has been teaching PharmD, BPharm, and MPharm students and conducting research in the novel drug delivery domain. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than twenty-four original journal articles, two edited books, four book chapters, and several scientific articles to his credit. He is a member of the American Association for Cancer Research, the International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. 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Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[{type:"book",id:"11672",title:"Chemokines Updates",subtitle:null,isOpenForSubmission:!0,hash:"c00855833476a514d37abf7c846e16e9",slug:null,bookSignature:"Prof. Murat Şentürk",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",editedByType:null,submissionDeadline:"May 6th 2022",editors:[{id:"14794",title:"Prof.",name:"Murat",middleName:null,surname:"Şentürk",slug:"murat-senturk",fullName:"Murat Şentürk",profilePictureURL:"https://mts.intechopen.com/storage/users/14794/images/system/14794.jpeg",biography:"Dr. Murat Şentürk obtained a baccalaureate degree in Chemistry in 2002, a master’s degree in Biochemistry in 2006, and a doctorate degree in Biochemistry in 2009 from Atatürk University, Turkey. Dr. Şentürk currently works as an professor of Biochemistry in the Department of Basic Pharmacy Sciences, Faculty of Pharmacy, Ağri Ibrahim Cecen University, Turkey. \nDr. Şentürk published over 120 scientific papers, reviews, and book chapters and presented several conferences to scientists. \nHis research interests span enzyme inhibitor or activator, protein expression, purification and characterization, drug design and synthesis, toxicology, and pharmacology. \nHis research work has focused on neurodegenerative diseases and cancer treatment. Dr. Şentürk serves as the editorial board member of several international journals.",institutionString:"Ağrı İbrahim Çeçen University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Ağrı İbrahim Çeçen University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}],selectedSeries:{title:"Infectious Diseases",id:"6"},selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:318,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/105823",hash:"",query:{},params:{id:"105823"},fullPath:"/profiles/105823",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()