Bone cells, their function, and locations [1, 2, 3, 4, 5, 6, 7].
\\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\\nIntechOpen 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.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'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\nDesigned 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\nAfter 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\nOur innovative Book Series format brings you:
\n\nIntechOpen 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\nIntechOpen 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.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"10356",leadTitle:null,fullTitle:"Natural Medicinal Plants",title:"Natural Medicinal Plants",subtitle:null,reviewType:"peer-reviewed",abstract:"This book, Natural Medicinal Plants is a comprehensive overview of drugs derived from medicinal plants and their use in treating human illnesses such as cancer. Chapters include scientific evidence on flora rich in active ingredients.",isbn:"978-1-83969-276-5",printIsbn:"978-1-83969-275-8",pdfIsbn:"978-1-83969-277-2",doi:"10.5772/intechopen.91542",price:139,priceEur:155,priceUsd:179,slug:"natural-medicinal-plants",numberOfPages:302,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"943e56ccaaf19ff696d25aa638ae37d6",bookSignature:"Hany A. El-Shemy",publishedDate:"May 11th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10356.jpg",numberOfDownloads:4373,numberOfWosCitations:0,numberOfCrossrefCitations:7,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:13,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:20,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 6th 2020",dateEndSecondStepPublish:"December 4th 2020",dateEndThirdStepPublish:"February 2nd 2021",dateEndFourthStepPublish:"April 23rd 2021",dateEndFifthStepPublish:"June 22nd 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy",profilePictureURL:"https://mts.intechopen.com/storage/users/54719/images/system/54719.jpg",biography:"Prof. Hany A. El-Shemy received a Ph.D. in Biochemistry from the University of Cairo, Egypt, and a Ph.D. in Genetic Engineering from the University of Hiroshima, Japan. He holds two patents and has written thirteen international books. He has also published more than 100 SCI journal papers and 55 conference presentations. Dr. El-Shemy was a technique committee member as well as chair of many international conferences. He has also served as editor for journals including PLOS ONE, BMC Genomics, and Current Issues in Molecular Biology. He has received several awards, including state prizes from the Academy of Science, Egypt (2004, 2012, and 2018), the Young Arab Researcher prize from the Shuman Foundation, Jordan (2005), and Cairo University Prizes (2007, 2010, and 2014). He served as an expert for the African Regional Center of Technology, Dakar, Senegal, as well as a visiting professor at Pan African University, African Union. He served as vice president of the Academy of Science and Technology, Egypt, from 2013 to 2014. Since 2014 he has been the dean of the Faculty of Agriculture, Cairo University. In 2018, he was elected a fellow of the African Academy of Science.",institutionString:"Cairo University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"13",institution:{name:"Cairo University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"991",title:"Herbalism",slug:"herbalism"}],chapters:[{id:"78514",title:"Natural Products Altering GABAergic Transmission",doi:"10.5772/intechopen.99500",slug:"natural-products-altering-gabaergic-transmission",totalDownloads:160,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Gamma-amino butyric acid (GABA) is a major inhibitory neurotransmitter found in several regions of the brain and known to have various significant physiological roles as a potent bioactive compound. Malfunction of GABAergic neuronal signaling prompts to cause severe psychiatric symptoms in numerous mental disorders. Several drugs are available in clinical practice for neuropsychiatric disorders targeting through GABAergic pathway, with notable adverse effects. Interestingly, in recent years, researchers are focusing on natural compounds altering GABAergic neurotransmission for various psychiatric disorders due to its wide range of therapeutic efficacy and safety. The enormous variety of natural compounds, namely alkaloids, flavonoids, terpenoids, polyacetylenic alcohols, alkanes and fatty acids were reported to alter the GABAergic transmission through its receptors and or by influencing the transmission, synthesis and metabolism of GABA. Natural compounds are able to cross the blood brain barrier and influence the GABA functions in order to treat anxiety, mania, schizophrenia and cognitive disorders. Therefore, this current chapter describes on natural products which have the potential to alter the GABAergic neurotransmission and its therapeutical benefits in treating several neuropsychiatry disorders using various pharmacological methods.",signatures:"Sayani Banerjee, Chennu Manisha, Deepthi Murugan and Antony Justin",downloadPdfUrl:"/chapter/pdf-download/78514",previewPdfUrl:"/chapter/pdf-preview/78514",authors:[{id:"344701",title:"Dr.",name:"Antony",surname:"Justin",slug:"antony-justin",fullName:"Antony Justin"},{id:"427929",title:"Dr.",name:"Sayani",surname:"Banerjee",slug:"sayani-banerjee",fullName:"Sayani Banerjee"},{id:"427930",title:"Dr.",name:"Chennu",surname:"Manisha",slug:"chennu-manisha",fullName:"Chennu Manisha"},{id:"427931",title:"Dr.",name:"Deepthi",surname:"Murugan",slug:"deepthi-murugan",fullName:"Deepthi Murugan"}],corrections:null},{id:"76353",title:"The Ghanaian Flora as a Potential Source of Anthelmintic and Anti-Schistosomal Agents",doi:"10.5772/intechopen.97417",slug:"the-ghanaian-flora-as-a-potential-source-of-anthelmintic-and-anti-schistosomal-agents",totalDownloads:221,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Parasitic infections including schistosomiasis and soil transmitted helminthiasis are the most commonly encountered Neglected Tropical Diseases (NTDs) in the world. These diseases remain a major public health concern affecting millions of people especially those living in poor regions where access to effective conventional health care is a challenge. Interventions to control these infections in endemic areas have not been successful due to the high cost of drugs, limited availability as well as inequity of access to preventive chemotherapies. Another problem is the development resistance to the limited number of recommended medications due to their intensive use in both human and live-stock. There is an increasing awareness of the potential of natural products as chemotherapeutic agents to combat parasitic infections. Natural products may offer an unlimited source of chemically diverse drug molecules which may be safe, efficient, less toxic, less expensive and readily available for use especially in low-income countries. The Ghanaian flora provides such a ready source for new therapeutic interventions for the local population. Several researches have provided evidence of the anti-parasitic activity of Ghanaian medicinal plants. This chapter provides a review with special focus on medicinal plants collected from Ghana with anthelmintic and anti-schistosomal activity. Evidence of pharmacological activities of crude extracts, fractions and bioactive phytoconstituents as well as possible mechanisms of action where investigated are discussed.",signatures:"Evelyn Asante-Kwatia, Abraham Yeboah Mensah, Lord Gyimah and Arnold Donkor Forkuo",downloadPdfUrl:"/chapter/pdf-download/76353",previewPdfUrl:"/chapter/pdf-preview/76353",authors:[{id:"217045",title:"Dr.",name:"Arnold Forkuo",surname:"Donkor",slug:"arnold-forkuo-donkor",fullName:"Arnold Forkuo Donkor"},{id:"303360",title:"Dr.",name:"Evelyn",surname:"Asante-Kwatia",slug:"evelyn-asante-kwatia",fullName:"Evelyn Asante-Kwatia"},{id:"309974",title:"Prof.",name:"Abraham Yeboah",surname:"Mensah",slug:"abraham-yeboah-mensah",fullName:"Abraham Yeboah Mensah"},{id:"347910",title:"Mr.",name:"Lord",surname:"Gyimah",slug:"lord-gyimah",fullName:"Lord Gyimah"}],corrections:[{id:"76505",title:"Corrigendum: The Ghanaian Flora as a Potential Source of Anthelmintic and Anti-Schistosomal Agents",doi:null,slug:"corrigendum-the-ghanaian-flora-as-a-potential-source-of-anthelmintic-and-anti-schistosomal-agents",totalDownloads:null,totalCrossrefCites:null,correctionPdfUrl:null}]},{id:"75561",title:"Traditional African Medicine",doi:"10.5772/intechopen.96576",slug:"traditional-african-medicine",totalDownloads:326,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"African traditional medicine is defined as one of the holistic health care system comprised of three levels of specializations namely divination, spiritualism, and herbalism. The traditional healer provides healing services based on culture, religious background, knowledge, attitudes, and beliefs that are prevalent in his community. Hence the current chapter focuses on the different types of african healing system, traditional healers, traditional practices and modern herbalism and also describes the phytochemical and pharmacological evidences of the traditional african herbs like Acanthus montanus (Acanthaceae), Amaranthus spinosus (Amaranthaceae), Bridelia ferruginea (Euphorbiaceae) etc.",signatures:"Motamarri V.N.L. Chaitanya, Hailemikael Gebremariam Baye, Heyam Saad Ali and Firehiwot Belayneh Usamo",downloadPdfUrl:"/chapter/pdf-download/75561",previewPdfUrl:"/chapter/pdf-preview/75561",authors:[{id:"339686",title:"Dr.",name:"Motamarri V.N.L.",surname:"Chaitanya",slug:"motamarri-v.n.l.-chaitanya",fullName:"Motamarri V.N.L. Chaitanya"},{id:"340066",title:"MSc.",name:"Firehiwot",surname:"Belayneh",slug:"firehiwot-belayneh",fullName:"Firehiwot Belayneh"},{id:"340068",title:"Prof.",name:"Heyam",surname:"Saad Ali",slug:"heyam-saad-ali",fullName:"Heyam Saad Ali"},{id:"348052",title:"BSc.",name:"Hailemikael",surname:"Gebremariam Baye",slug:"hailemikael-gebremariam-baye",fullName:"Hailemikael Gebremariam Baye"}],corrections:null},{id:"76298",title:"Ethnomedicine Study on Medicinal Plants Used by Communities in West Sumatera, Indonesia",doi:"10.5772/intechopen.96810",slug:"ethnomedicine-study-on-medicinal-plants-used-by-communities-in-west-sumatera-indonesia",totalDownloads:151,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Currently, the development of conventional medicine is getting more advanced, it cannot be denied that medicinal plants still occupy their main role as medicine for various human diseases, especially in developing countries. This is rooted in the knowledge of the local community about plants that can be used as medicine for various diseases. Ethnomedicine is a field of study that raises local knowledge of the community to maintain their health. From numerous studies on the field, 33 species of plants have been found which are believed by the natives to West Sumatra as medicine. Ethnomedicinal data were analyzed using Index of Cultural Significance (ICS) value. The results of the analysis showed that the species of plants that is voted most important for the community were soursop (Annona muricata) and red betel (Piper sp.). In general, the part of plant that is most often used as medicine is the leaf, and the way to consume it is by boiling it so that you can get the herbs from the plant extract.",signatures:"Skunda Diliarosta, Monica Prima Sari, Rehani Ramadhani and Annisa Efendi",downloadPdfUrl:"/chapter/pdf-download/76298",previewPdfUrl:"/chapter/pdf-preview/76298",authors:[{id:"342268",title:"Dr.",name:"Skunda",surname:"Diliarosta",slug:"skunda-diliarosta",fullName:"Skunda Diliarosta"},{id:"346504",title:"Ms.",name:"Rehani",surname:"Ramadhani",slug:"rehani-ramadhani",fullName:"Rehani Ramadhani"},{id:"346505",title:"Ms.",name:"Annisa",surname:"Efendi",slug:"annisa-efendi",fullName:"Annisa Efendi"},{id:"346920",title:"Mrs.",name:"Monica",surname:"Prima Sari",slug:"monica-prima-sari",fullName:"Monica Prima Sari"}],corrections:null},{id:"75771",title:"Advanced Pharmacological Uses of Marine Algae as an Anti-Diabetic Therapy",doi:"10.5772/intechopen.96807",slug:"advanced-pharmacological-uses-of-marine-algae-as-an-anti-diabetic-therapy",totalDownloads:232,totalCrossrefCites:2,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Marine seaweeds are a promising source of bioactive secondary metabolites that can be utilized in drug development and nutraceuticals. Diabetes mellitus is a leading non-communicable disease, and it is the third leading cause of death worldwide. Among the types of diabetes, type 2 became the major health problem as it is associated with severe health complications. Since available oral hypoglycemic drugs cause several adverse effects, it is worth searching for a natural cure with fewer or no side effects that may benefit patients with type 2 diabetes. Among the marine seaweeds, brown and red seaweeds are extensively studied for the anti-diabetic activity compared to the green seaweeds. Bioactive compounds present in marine seaweeds possess anti-diabetic potential through diverse mechanisms, mainly by reducing postprandial hyperglycemia and associated complication. Most of the studies emphasized that the marine seaweeds control the hyperglycemic condition by inhibiting carbohydrate hydrolyzing α-amylase,α glucosidase enzymes, and the inhibitory effect of dipeptide peptidase-4 that are involved in the degradation of incretins. Similarly, bioactive compounds in marine seaweeds can reduce diabetes complications by inhibiting angiotensin-converting enzymes, aldose reductase, protein tyrosine phosphatase 1B enzyme. This chapter focuses on the anti-diabetic potential of marine brown, green, and red seaweeds through different mechanisms.",signatures:"Thilina Gunathilaka, Lakshika Rangee Keertihirathna and Dinithi Peiris",downloadPdfUrl:"/chapter/pdf-download/75771",previewPdfUrl:"/chapter/pdf-preview/75771",authors:[{id:"219479",title:"Prof.",name:"Dinithi",surname:"Peiris",slug:"dinithi-peiris",fullName:"Dinithi Peiris"},{id:"343219",title:"Mrs.",name:"Thilina",surname:"Gunathilaka",slug:"thilina-gunathilaka",fullName:"Thilina Gunathilaka"},{id:"356401",title:"Dr.",name:"Lakshika Rangee",surname:"Keerthirathna",slug:"lakshika-rangee-keerthirathna",fullName:"Lakshika Rangee Keerthirathna"}],corrections:null},{id:"75758",title:"Safety Review of Herbs and Supplements in Heart Disease, Diabetes, and COVID-19",doi:"10.5772/intechopen.96811",slug:"safety-review-of-herbs-and-supplements-in-heart-disease-diabetes-and-covid-19",totalDownloads:230,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Usage of supplements has increased dramatically this last decade. From herbs to vitamins and mineral, consumers are interested in improving health, self-treatment and preventing diseases. Often using information from the internet to self-prescribe, many consumers believe that natural products are safe, while many others avoid using these products because of the lack of an approval process by health officials in many countries. Herbs and other supplements including proteins, vitamins and minerals provide significant benefits to health. The lack of guidance from health professionals however can be problematic. When combined with drugs and disease, herbs can interact and cause side effects. Some of the steps to evaluate the safe use of supplements is to know their mechanism of action, clinical effect, and consumers’ medical history. For example, an herb that induces liver enzymes will reduce the effect of a drug that is metabolized by these same enzymes. This can be life threating if the patient depends on this drug for normal function. Based on drug-herb interaction experience and literature review, this book chapter provides insights into safe use of echinacea, licorice, turmeric, and black seed in patients with heart disease, diabetes, and COVID-19.",signatures:"Paula Vieira-Brock",downloadPdfUrl:"/chapter/pdf-download/75758",previewPdfUrl:"/chapter/pdf-preview/75758",authors:[{id:"343363",title:"Ph.D.",name:"Paula",surname:"Vieira-Brock",slug:"paula-vieira-brock",fullName:"Paula Vieira-Brock"}],corrections:null},{id:"76486",title:"Pharmacological Investigation of Genus Pistacia",doi:"10.5772/intechopen.97322",slug:"pharmacological-investigation-of-genus-em-pistacia-em-",totalDownloads:200,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Several plants in the genus Pistacia are used in the treatment of various pathogenic and non-pathogenic disorders. Especially important are the major species belonging to this genus such as Pistacia lentiscus, Pistacia atlantica, Pistacia vera, Pistacia terebinthus, and Pistacia khinjuk, among others; these have been reported for their potential benefits both in medical and commercial purposes. In addition, members of this genus exhibit numerous ethnomedicinal uses, such as analgesic, anti-inflammatory, anticancer, antimicrobial, antihypertension, antihyperlipidemic, antiviral, and antiasthma. In light of these potential uses, the present chapter aimed to collect and summarize the literature about all of this medicinal information. Accordingly, this chapter focuses on the pharmacological uses and benefits of the genus Pistacia, especially those related to health issues.",signatures:"Abdur Rauf, Yahya S. Al-Awthan, Naveed Muhammad, Muhammad Mukarram Shah, Saikat Mitra, Talha Bin Emran, Omar Bahattab and Mohammad S. Mubarak",downloadPdfUrl:"/chapter/pdf-download/76486",previewPdfUrl:"/chapter/pdf-preview/76486",authors:[{id:"192295",title:"Dr.",name:"Abdur",surname:"Rauf",slug:"abdur-rauf",fullName:"Abdur Rauf"},{id:"207131",title:"Prof.",name:"Mohammad S.",surname:"Mubarak",slug:"mohammad-s.-mubarak",fullName:"Mohammad S. Mubarak"},{id:"348414",title:"Dr.",name:"Yahya",surname:"Al-Awthan",slug:"yahya-al-awthan",fullName:"Yahya Al-Awthan"},{id:"348415",title:"Dr.",name:"Naveed",surname:"Muhammad",slug:"naveed-muhammad",fullName:"Naveed Muhammad"},{id:"348417",title:"Prof.",name:"Muhammad",surname:"Mukarram Shah",slug:"muhammad-mukarram-shah",fullName:"Muhammad Mukarram Shah"},{id:"348418",title:"Dr.",name:"Saikat",surname:"Mitra",slug:"saikat-mitra",fullName:"Saikat Mitra"},{id:"348419",title:"Dr.",name:"Talha",surname:"Bin Emran",slug:"talha-bin-emran",fullName:"Talha Bin Emran"},{id:"348420",title:"Dr.",name:"Omar",surname:"Bahattab",slug:"omar-bahattab",fullName:"Omar Bahattab"}],corrections:null},{id:"77125",title:"Medicinal Plants and Traditional Practices of Baiga Tribe in Amarkantak Region of Eastern Madhya Pradesh",doi:"10.5772/intechopen.97697",slug:"medicinal-plants-and-traditional-practices-of-baiga-tribe-in-amarkantak-region-of-eastern-madhya-pra",totalDownloads:223,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The present ethnobotanical study was carried out in Amarkantak region eastern part of Madhya Pradesh during January 2018 to January 2019 to document the medicinal plants used by the Baiga tribes. Traditional medicinal plants used by the Baiga tribes of 37 plant species belonging to 35 genera and 28 families used to menstrual disorder, piles, sore throat, respiratory disorder, haematuria, miscarriage, jaundice, fever, insanity, leucorrhoea, bleeding during pregnancy, spermatorrhea, infertility in women, motiabind, scorpion bite, wounds of animals, stomach disorder, intestinal worms, diabetes, leukoderma, rheumatism, scabies, wart and easy delivery etc. and other various unreported medicinal plants are reported here.",signatures:"Ramesh Kumar Ahirwar",downloadPdfUrl:"/chapter/pdf-download/77125",previewPdfUrl:"/chapter/pdf-preview/77125",authors:[{id:"340104",title:"Dr.",name:"Ramesh",surname:"Kumar Ahirwar",slug:"ramesh-kumar-ahirwar",fullName:"Ramesh Kumar Ahirwar"}],corrections:null},{id:"77433",title:"Extraction of Bioactive Compounds from Medicinal Plants and Herbs",doi:"10.5772/intechopen.98602",slug:"extraction-of-bioactive-compounds-from-medicinal-plants-and-herbs",totalDownloads:1312,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:1,abstract:"Human beings have relied on herbs and medicinal plants as sources of food and remedy from time immemorial. Bioactive compounds from plants are currently the subject of much research interest, but their extraction as part of phytochemical and/or biological investigations present specific challenges. Herbalists or scientists have developed many protocols of extraction of bioactive ingredients to ensure the effectiveness and the efficacy of crude drugs that were used to get relief from sickness. With the advent of new leads from plants such as morphine, quinine, taxol, artemisinin, and alkaloids from Voacanga species, a lot of attention is paid to the mode of extraction of active phytochemicals to limit the cost linked to the synthesis and isolation. Thus, the extraction of active compounds from plants needs appropriate extraction methods and techniques that provide bioactive ingredients-rich extracts and fractions. The extraction procedures, therefore, play a critical role in the yield, the nature of phytochemical content, etc. This chapter aims to present, describe, and compare extraction procedures of bioactive compounds from herbs and medicinal plants.",signatures:"Fongang Fotsing Yannick Stéphane, Bankeu Kezetas Jean Jules, Gaber El-Saber Batiha, Iftikhar Ali and Lenta Ndjakou Bruno",downloadPdfUrl:"/chapter/pdf-download/77433",previewPdfUrl:"/chapter/pdf-preview/77433",authors:[{id:"224515",title:"Dr.",name:"Fongang Fotsing",surname:"Yannick Stéphane",slug:"fongang-fotsing-yannick-stephane",fullName:"Fongang Fotsing Yannick Stéphane"},{id:"227816",title:"Dr.",name:"Bankeu Kezetas",surname:"Jean Jules",slug:"bankeu-kezetas-jean-jules",fullName:"Bankeu Kezetas Jean Jules"},{id:"227817",title:"Prof.",name:"Lenta Ndjakou",surname:"Bruno",slug:"lenta-ndjakou-bruno",fullName:"Lenta Ndjakou Bruno"},{id:"349790",title:"Prof.",name:"Gaber",surname:"El-Saber Batiha",slug:"gaber-el-saber-batiha",fullName:"Gaber El-Saber Batiha"},{id:"357350",title:"Dr.",name:"Iftikhar",surname:"Ali",slug:"iftikhar-ali",fullName:"Iftikhar Ali"}],corrections:null},{id:"77108",title:"Controversy, Adulteration and Substitution: Burning Problems in Ayurveda Practices",doi:"10.5772/intechopen.98220",slug:"controversy-adulteration-and-substitution-burning-problems-in-ayurveda-practices",totalDownloads:232,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Ayurveda is an Indian traditional system of medicine. In present era, world is looking towards herbal medicine because of acceptability and safety. Medicinal plants constitute an effective source of Ayurvedic and other traditional system of medicines as well as modern medicine. In India, about 80% of the rural population depends on herbal medicines in primary health care level. A large percentage of plants used in herbal industries are subject of controversy. Non-availability of plants, poor understanding and parallel evolved knowledge systems are some of the reasons attributed to it. The existing practices of polynomial nomenclature system of Sanskrit, different perceptions in various communities, vernacular equivalents, all are cumulative factors for controversy, adulteration and substitution. “ Sandigdha Dravaya “ is a term used for that type of medicinal plants which are mentioned in Ayurvedic classics but their exact botanical source is not known. Adulterants and substitutes are the common practices in herbal raw material trade. Adulteration is a debasement of an article. The motives for intentional adulteration are normally commercial that which involves deterioration, admixture, sophistication, inferiority, spoilage and other unknown reasons. Substitution is a replacement of equivalent drugs in place of original drugs. The principles to select substitute drugs are based on similar Rasa, Guna, Virya, Vipaka and mainly the Karma. At present the adulteration and Substitution of the herbal drugs is the burning problem in herbal industry and in Ayurvedic practices. So it is necessary to develop reliable methodologies for correct identification, standardization and quality assurance of Ayurvedic drugs.",signatures:"Puneshwar Keshari",downloadPdfUrl:"/chapter/pdf-download/77108",previewPdfUrl:"/chapter/pdf-preview/77108",authors:[{id:"339545",title:"Dr.",name:"Puneshwar",surname:"Keshari",slug:"puneshwar-keshari",fullName:"Puneshwar Keshari"}],corrections:null},{id:"76024",title:"Phytochemical Profile and Antiobesity Potential of Momordica charantia Linn.",doi:"10.5772/intechopen.96808",slug:"phytochemical-profile-and-antiobesity-potential-of-em-momordica-charantia-em-linn-",totalDownloads:176,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Momordica charantia L. is growing in many tropical and subtropical regions; the fruits of bitter melon are also gradually becoming popular for treating diabetes and associated diseases. Over 248 compounds belonging to the lipids, phenolics and terpenoids class are reported by diverse studies. However, M. charantia L. appears to be an inimitable species that synthesizes a diverse range of natural products in the fruits, leaves, stems and roots. The cucurbitane types of triterpenes exist in the various tissues of the plant in their aglycone as well as glycosylated forms. The bitter melon seems to exert their lipid lowering and antiobesity effects via several mechanisms like PPARs, LXRs, SREBPs, and Sirts mediated fat metabolism in various tissues, prevent adipocyte hypertrophy and visceral fat accumulation. M. charantia L. has been comprehensively studied worldwide for its therapeutic properties to treat a number of diseases like diabetes, dyslipidaemia, obesity, and certain cancers. This chapter apparently displays an encompassing literature review on vast potential of bitter melon as antiobesity agent and assembles data on complex phytochemistry.",signatures:"Pushpa Anantrao Karale, Shashikant Dhawale and Mahesh Karale",downloadPdfUrl:"/chapter/pdf-download/76024",previewPdfUrl:"/chapter/pdf-preview/76024",authors:[{id:"340628",title:"Ph.D. Student",name:"Pushpa",surname:"Anantrao Karale",slug:"pushpa-anantrao-karale",fullName:"Pushpa Anantrao Karale"},{id:"346847",title:"Dr.",name:"Shashikant",surname:"Dhawale",slug:"shashikant-dhawale",fullName:"Shashikant Dhawale"},{id:"346907",title:"Dr.",name:"Mahesh",surname:"Karale",slug:"mahesh-karale",fullName:"Mahesh Karale"}],corrections:null},{id:"79065",title:"Medicinal Plants and Its Pharmacological Values",doi:"10.5772/intechopen.99848",slug:"medicinal-plants-and-its-pharmacological-values",totalDownloads:184,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Plants have been used as a source of medicine for the treatment of different diseases from thousands of years ago. There is numerous evidences are available for use of plants as a medicine in the treatment of diseases in Indian, Egyptian, Chinese, Greek and Roman system of medicine. Pharmacognosy is the study of medicines derived from natural sources, mainly from plants which may further lead to development of new drug. The exploration, extraction and screening of biological diversity such as herbs, spices, microbes and other natural resources is the worldwide activity in recent years. Phytochemicals are the naturally available bioactive compounds which are derived from different plant parts and are primarily responsible for biological activities. The most important chemical compounds which are present in the plants are alkaloids, phenols, saponins, carbohydrates, terpenoids, steroids, flavonoids and tannins etc.",signatures:"Smita G. Bhat",downloadPdfUrl:"/chapter/pdf-download/79065",previewPdfUrl:"/chapter/pdf-preview/79065",authors:[{id:"343927",title:"Ph.D. Student",name:"Smita G.",surname:"Bhat",slug:"smita-g.-bhat",fullName:"Smita G. Bhat"}],corrections:null},{id:"78916",title:"Traditional Usage of Plants of Costus Species in Assam, India",doi:"10.5772/intechopen.100532",slug:"traditional-usage-of-plants-of-costus-species-in-assam-india",totalDownloads:135,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Customary use of plants in the treatment of ailments in Assam, India is a typical situation. Ethno medicinal study was led in a few topographically unique zones of the state and utilization of plants from Costus species were reported. The extent of study chose for the investigation range across seven organizational regions spread across Assam, India. The regions include Dibrugarh, Golaghat, Tinsukia, Dhemaji, Karbi Anglong, Goalpara and Kokrajhar. Different plants were reported and plants fitting with the said species were chosen for determining the relevance concerning its use in customary medication. The survey divulged that plants associated to three species of the genus Costus namely Costus speciosus, Costus pictus and Costus scaber were espied to be primarily ubiquitous in traditional medicine in the discrete contemplated regions. The species were predominantly utilized as prime ingrediants in hepatoprotactive and anti-diabetic formulations. Costus speciosus was perceived to be chiefly used in the treatment of hepatic disorders and ailments. Costus pictus was observed to be used customarily in the upper Assam region bordering Nagaland for treating diabetes and Costus scaber was being used in the area bordering Arunachal Pradesh for tending people with jaundice, snake bite etc. The research climaxed with the profiling of the costus species as annotated from the ethnomedicinal survey.",signatures:"Biman Bhuyan, Dipak Chetia and Prakash Rajak",downloadPdfUrl:"/chapter/pdf-download/78916",previewPdfUrl:"/chapter/pdf-preview/78916",authors:[{id:"272268",title:"Prof.",name:"Biman",surname:"Bhuyan",slug:"biman-bhuyan",fullName:"Biman Bhuyan"},{id:"420787",title:"Mr.",name:"Prakash",surname:"Rajak",slug:"prakash-rajak",fullName:"Prakash Rajak"},{id:"420788",title:"Prof.",name:"Dipak",surname:"Chetia",slug:"dipak-chetia",fullName:"Dipak Chetia"}],corrections:null},{id:"76563",title:"Benefaction of Medicinal Plant Uraria picta",doi:"10.5772/intechopen.97731",slug:"benefaction-of-medicinal-plant-em-uraria-picta-em-",totalDownloads:27,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Medicinal plants are very significant as they not only maintain the health and vitality but most importantly also cure the various ailments in humans and animals without causing any toxic side effects. These are readily available and cost effective therapeutic agents. Uraria picta was first proposed by Desvaux, (1813), is highly medicinal and critically endangered plant species found throughout India and other parts of the world like Africa, Australia, Philippines, Malaysia, Japan, Nigeria etc. This herb is full of antiseptic, anti-inflammatory, antimicrobial, anti-emetic, aphrodisiac, analgesic, cardiovascular and expectorant properties. Due to its high therapeutic use and growing need, the plant is becoming rare and endangered, therefore it is necessary to create awareness of this plant to support its propagation in large numbers. This herb also shows properties of anti-cancer and anti-cholinergic properties hence can manage depressions, anxiety, sleeping problems. Analgesic property helps in reducing body pain.",signatures:"Harsha Kashyap",downloadPdfUrl:"/chapter/pdf-download/76563",previewPdfUrl:"/chapter/pdf-preview/76563",authors:[{id:"341318",title:"Dr.",name:"Harsha",surname:"Kashyap",slug:"harsha-kashyap",fullName:"Harsha Kashyap"}],corrections:null},{id:"75500",title:"Spices-Reservoir of Health Benefits",doi:"10.5772/intechopen.96471",slug:"spices-reservoir-of-health-benefits",totalDownloads:224,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Spices contribute to the quality, nutritive value, and flavor of food. Since ancient times, they hold a great medicinal value. Their antimicrobial, antiviral, antibacterial, anti-inflammatory, and other numerous properties have made them a potent source of therapeutic agents. Phytochemical analysis revealed presence of active constituents such as eugenol, curcumin, carotenoids in clove, turmeric, saffron respectively that explains the efficacious nature of these spices. Owing to their easy availability and consumption, it is advised to make spices daily part of our diet though in balanced amount as sometimes excess usage bear few consequences. Evaluating multiple benefits offered by these as immunity boosters especially in times of pandemic and incorporating them in our routine diet would improve disease management strategies. This chapter discusses the reservoir of activities exhibited by few spices along with the components responsible for these activities. Here, we also discussed their negative effects if at all.",signatures:"Cheryl Sachdeva and Naveen Kumar Kaushik",downloadPdfUrl:"/chapter/pdf-download/75500",previewPdfUrl:"/chapter/pdf-preview/75500",authors:[{id:"341343",title:"Assistant Prof.",name:"Naveen Kumar",surname:"Kaushik",slug:"naveen-kumar-kaushik",fullName:"Naveen Kumar Kaushik"},{id:"341345",title:"Ms.",name:"Cheryl",surname:"Sachdeva",slug:"cheryl-sachdeva",fullName:"Cheryl Sachdeva"}],corrections:null},{id:"75373",title:"Historical Evidence and Documentation of Remedial Flora of Azad Jammu and Kashmir (AJK)",doi:"10.5772/intechopen.96472",slug:"historical-evidence-and-documentation-of-remedial-flora-of-azad-jammu-and-kashmir-ajk-",totalDownloads:344,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Determining the pharmacognostic specifications of medicinal plants used in several drugs is very necessary and actually crucial. Ethnobotany has significant role in understanding the active relations between the biological diversity and cultural systems. Azad Jammu and Kashmir (AJK) is gifted with variety of medicinal plants. The theme of this chapter is to present information about wild medicinal plants in different areas of Azad Jammu and Kashmir. Common woody species are Diospyros lotus, Taxus wallichiana, Viburnum cylindricum, and perennial herbs comprise Geranium nepalense, Oxalis acetosella and Androsace umbellata. Betula utilis, Berberis lycium, Cedrus deodara, Abies pindrow, Pinus wallichiana, Juglans regia and Salix species with large number of herbal diversity at elevations are common. Most of people use wild plants as traditional food and medicine. This ethnic flora not only plays important role in human health care but it is also an important source for present and future drug development. There is need for correct documentation, conservation of plants samples in herbarium of research institutes, and growing plants in gardens.",signatures:"Fozia Abasi, Muhammad Shoaib Amjad and Huma Qureshi",downloadPdfUrl:"/chapter/pdf-download/75373",previewPdfUrl:"/chapter/pdf-preview/75373",authors:[{id:"343051",title:"Dr.",name:"Muhammad Shoaib",surname:"Amjad",slug:"muhammad-shoaib-amjad",fullName:"Muhammad Shoaib Amjad"},{id:"343054",title:"Ms.",name:"Fozia",surname:"Abasi",slug:"fozia-abasi",fullName:"Fozia Abasi"},{id:"343057",title:"Dr.",name:"Huma",surname:"Qureshi",slug:"huma-qureshi",fullName:"Huma Qureshi"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"497",title:"Soybean and Nutrition",subtitle:null,isOpenForSubmission:!1,hash:"11aa0c9ed0f6ea8da765be93b50954bb",slug:"soybean-and-nutrition",bookSignature:"Hany El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/497.jpg",editedByType:"Edited by",editors:[{id:"54719",title:"Prof.",name:"Hany",surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"496",title:"Soybean and Health",subtitle:null,isOpenForSubmission:!1,hash:"66d40dbc031b2825ba95f7ac2bfae1b6",slug:"soybean-and-health",bookSignature:"Hany El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/496.jpg",editedByType:"Edited by",editors:[{id:"54719",title:"Prof.",name:"Hany",surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3244",title:"Soybean",subtitle:"Bio-Active Compounds",isOpenForSubmission:!1,hash:"b21aa6107fce439bd06d53fbe0bc3c9e",slug:"soybean-bio-active-compounds",bookSignature:"Hany A. 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Physical ergonomics is concerned with the consequences of repetitive motion, materials handling, workplace safety, comfort in the use of portable devices, keyboard design, working postures, and the work environment. Cognitive ergonomics deals with the mental (intellectual and psychological) aspects of the operator-activity relationship: perception, reasoning, memory, stimuli, psycho-motor responses, etc. Organizational ergonomics is concerned with the optimization of sociotechnical systems, including their organizational structures, policies, and processes.
\r\n\r\n\tThis book is designed to provide an extensive literature review, uncover contemporary research, and shed a light on the researchers in all three fields of ergonomics.
",isbn:"978-1-80356-471-5",printIsbn:"978-1-80356-470-8",pdfIsbn:"978-1-80356-472-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"8b7474730a8f1ec6615e66e12a72b4b5",bookSignature:"Dr. Orhan Korhan",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11877.jpg",keywords:"Workplace Safety, Repetitive Strain Injuries, Vibration, Posture, Materials Handling, Work Environment, Cognitive Ergonomics, Communication, Work Design, Community Ergonomics, Telework, Quality Management",numberOfDownloads:16,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 3rd 2022",dateEndSecondStepPublish:"May 6th 2022",dateEndThirdStepPublish:"July 5th 2022",dateEndFourthStepPublish:"September 23rd 2022",dateEndFifthStepPublish:"November 22nd 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"An active researcher and full professor in Industrial Engineering, appointed to be the director of Industry 4.0 Research Center, Vice-Dean of Faculty of Engineering, author of several articles, chapters, and books, and editor of several books in Ergonomics.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"101698",title:"Dr.",name:"Orhan",middleName:null,surname:"Korhan",slug:"orhan-korhan",fullName:"Orhan Korhan",profilePictureURL:"https://mts.intechopen.com/storage/users/101698/images/system/101698.jpeg",biography:"Orhan Korhan graduated with a BS from Eastern Mediterranean University (EMU) in 2000, a MS from the University of Louisville in 2002, and a PhD from EMU in Industrial Engineering in 2010. He has been working at EMU since 2009. He became Assistant Professor in 2010, and Associate Professor in 2014, and a full Professor in 2020. He has been assigned to scientific committee of several international conferences, published several books, book chapters, and papers in various countries. His current research interests include Work-related Musculoskeletal Disorders, Cognitive Ergonomics, Industry 4.0 and Facilities Planning and Design.",institutionString:"Eastern Mediterranean University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Eastern Mediterranean University",institutionURL:null,country:{name:"Cyprus"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:[{id:"81577",title:"Musculoskeletal Disorders in the Teaching Profession",slug:"musculoskeletal-disorders-in-the-teaching-profession",totalDownloads:16,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444312",firstName:"Sara",lastName:"Tikel",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/444312/images/20015_n.jpg",email:"sara.t@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"64747",title:"Bone Development and Growth",doi:"10.5772/intechopen.82452",slug:"bone-development-and-growth",body:'Bone is living tissue that is the hardest among other connective tissues in the body, consists of 50% water. The solid part remainder consisting of various minerals, especially 76% of calcium salt and 33% of cellular material. Bone has vascular tissue and cellular activity products, especially during growth which is very dependent on the blood supply as basic source and hormones that greatly regulate this growth process. Bone-forming cells, osteoblasts, osteoclast play an important role in determining bone growth, thickness of the cortical layer and structural arrangement of the lamellae.
Bone continues to change its internal structure to reach the functional needs and these changes occur through the activity of osteoclasts and osteoblasts. The bone seen from its development can be divided into two processes: first is the intramembranous ossification in which bones form directly in the form of primitive mesenchymal connective tissue, such as the mandible, maxilla and skull bones. Second is the endochondral ossification in which bone tissue replaces a preexisting hyaline cartilage, for example during skull base formation. The same formative cells form two types of bone formation and the final structure is not much different.
Bone growth depends on genetic and environmental factors, including hormonal effects, diet and mechanical factors. The growth rate is not always the same in all parts, for example, faster in the proximal end than the distal humerus because the internal pattern of the spongiosum depends on the direction of bone pressure. The direction of bone formation in the epiphysis plane is determined by the direction and distribution of the pressure line. Increased thickness or width of the bone is caused by deposition of new bone in the form of circumferential lamellae under the periosteum. If bone growth continues, the lamella will be embedded behind the new bone surface and be replaced by the haversian canal system.
Bone is a tissue in which the extracellular matrix has been hardened to accommodate a supporting function. The fundamental components of bone, like all connective tissues, are cells and matrix. Although bone cells compose a small amount of the bone volume, they are crucial to the function of bones. Four types of cells are found within bone tissue: osteoblasts, osteocytes, osteogenic cells, and osteoclasts. They each unique functions and are derived from two different cell lines (Figure 1 and Table 1) [1, 2, 3, 4, 5, 6, 7].
Osteoblast synthesizes the bone matrix and are responsible for its mineralization. They are derived from osteoprogenitor cells, a mesenchymal stem cell line.
Osteocytes are inactive osteoblasts that have become trapped within the bone they have formed.
Osteoclasts break down bone matrix through phagocytosis. Predictably, they ruffled border, and the space between the osteoblast and the bone is known as Howship’s lacuna.
Development of bone precursor cells. Bone precursor cells are divided into developmental stages, which are 1. mesenchymal stem cell, 2. pre-osteoblast, 3. osteoblast, and 4. mature osteocytes, and 5. osteoclast.
The balance between osteoblast and osteoclast activity governs bone turnover and ensures that bone is neither overproduced nor overdegraded. These cells build up and break down bone matrix, which is composed of:
Osteoid, which is the unmineralized matrix composed of type I collagen and gylcosaminoglycans (GAGs).
Calcium hydroxyapatite, a calcium salt crystal that give bone its strength and rigidity.
Bone is divided into two types that are different structurally and functionally. Most bones of the body consist of both types of bone tissue (Figure 2) [1, 2, 8, 9]:
Compact bone, or cortical bone, mainly serves a mechanical function. This is the area of bone to which ligaments and tendons attach. It is thick and dense.
Trabecular bone, also known as cancellous bone or spongy bone, mainly serves a metabolic function. This type of bone is located between layers of compact bone and is thin porous. Location within the trabeculae is the bone marrow.
Structure of a long bone.
Long bones are composed of both cortical and cancellous bone tissue. They consist of several areas (Figure 3) [3, 4]:
The epiphysis is located at the end of the long bone and is the parts of the bone that participate in joint surfaces.
The diaphysis is the shaft of the bone and has walls of cortical bone and an underlying network of trabecular bone.
The epiphyseal growth plate lies at the interface between the shaft and the epiphysis and is the region in which cartilage proliferates to cause the elongation of the bone.
The metaphysis is the area in which the shaft of the bone joins the epiphyseal growth plate.
Bone macrostructure. (a) Growing long bone showing epiphyses, epiphyseal plates, metaphysis and diaphysis. (b) Mature long bone showing epiphyseal lines.
Different areas of the bone are covered by different tissue [4]:
The epiphysis is lined by a layer of articular cartilage, a specialized form of hyaline cartilage, which serves as protection against friction in the joints.
The outside of the diaphysis is lined by periosteum, a fibrous external layer onto which muscles, ligaments, and tendons attach.
The inside of the diaphysis, at the border between the cortical and cancellous bone and lining the trabeculae, is lined by endosteum.
Compact bone is organized as parallel columns, known as Haversian systems, which run lengthwise down the axis of long bones. These columns are composed of lamellae, concentric rings of bone, surrounding a central channel, or Haversian canal, that contains the nerves, blood vessels, and lymphatic system of the bone. The parallel Haversian canals are connected to one another by the perpendicular Volkmann’s canals.
The lamellae of the Haversian systems are created by osteoblasts. As these cells secrete matrix, they become trapped in spaces called lacunae and become known as osteocytes. Osteocytes communicate with the Haversian canal through cytoplasmic extensions that run through canaliculi, small interconnecting canals (Figure 4) [1, 2, 8, 9]:
Bone microstructure. Compact and spongy bone structures.
The layers of a long bone, beginning at the external surface, are therefore:
Periosteal surface of compact bone
Outer circumferential lamellae
Compact bone (Haversian systems)
Inner circumferential lamellae
Endosteal surface of compact bone
Trabecular bone
Bone development begins with the replacement of collagenous mesenchymal tissue by bone. This results in the formation of woven bone, a primitive form of bone with randomly organized collagen fibers that is further remodeled into mature lamellar bone, which possesses regular parallel rings of collagen. Lamellar bone is then constantly remodeled by osteoclasts and osteoblasts. Based on the development of bone formation can be divided into two parts, called endochondral and intramembranous bone formation/ossification [1, 2, 3, 8].
During intramembranous bone formation, the connective tissue membrane of undifferentiated mesenchymal cells changes into bone and matrix bone cells [10]. In the craniofacial cartilage bones, intramembranous ossification originates from nerve crest cells. The earliest evidence of intramembranous bone formation of the skull occurs in the mandible during the sixth prenatal week. In the eighth week, reinforcement center appears in the calvarial and facial areas in areas where there is a mild stress strength [11].
Intramembranous bone formation is found in the growth of the skull and is also found in the sphenoid and mandible even though it consists of endochondral elements, where the endochondral and intramembranous growth process occurs in the same bone. The basis for either bone formation or bone resorption is the same, regardless of the type of membrane involved.
Sometimes according to where the formation of bone tissue is classified as “periosteal” or “endosteal”. Periosteal bone always originates from intramembranous, but endosteal bone can originate from intramembranous as well as endochondral ossification, depending on the location and the way it is formed [3, 12].
The statement below is the stage of intramembrane bone formation (Figure 5) [3, 4, 11, 12]:
An ossification center appears in the fibrous connective tissue membrane. Mesenchymal cells in the embryonic skeleton gather together and begin to differentiate into specialized cells. Some of these cells differentiate into capillaries, while others will become osteogenic cells and osteoblasts, then forming an ossification center.
Bone matrix (osteoid) is secreted within the fibrous membrane. Osteoblasts produce osteoid tissue, by means of differentiating osteoblasts from the ectomesenchyme condensation center and producing bone fibrous matrix (osteoid). Then osteoid is mineralized within a few days and trapped osteoblast become osteocytes.
Woven bone and periosteum form. The encapsulation of cells and blood vessels occur. When osteoid deposition by osteoblasts continues, the encased cells develop into osteocytes. Accumulating osteoid is laid down between embryonic blood vessels, which form a random network (instead of lamellae) of trabecular. Vascularized mesenchyme condenses on external face of the woven bone and becomes the periosteum.
Production of osteoid tissue by membrane cells: osteocytes lose their ability to contribute directly to an increase in bone size, but osteoblasts on the periosteum surface produce more osteoid tissue that thickens the tissue layer on the existing bone surface (for example, appositional bone growth). Formation of a woven bone collar that is later replaced by mature lamellar bone. Spongy bone (diploe), consisting of distinct trabeculae, persists internally and its vascular tissue becomes red marrow.
Osteoid calcification: The occurrence of bone matrix mineralization makes bones relatively impermeable to nutrients and metabolic waste. Trapped blood vessels function to supply nutrients to osteocytes as well as bone tissue and eliminate waste products.
The formation of an essential membrane of bone which includes a membrane outside the bone called the bone endosteum. Bone endosteum is very important for bone survival. Disruption of the membrane or its vascular tissue can cause bone cell death and bone loss. Bones are very sensitive to pressure. The calcified bones are hard and relatively inflexible.
The stage of intramembranous ossification. The following stages are (a) Mesenchymal cells group into clusters, and ossification centers form. (b) Secreted osteoid traps osteoblasts, which then become osteocytes. (c) Trabecular matrix and periosteum form. (d) Compact bone develops superficial to the trabecular bone, and crowded blood vessels condense into red marrow.
The matrix or intercellular substance of the bone becomes calcified and becomes a bone in the end. Bone tissue that is found in the periosteum, endosteum, suture, and periodontal membrane (ligaments) is an example of intramembranous bone formation [3, 13].
Intramembranous bone formation occurs in two types of bone: bundle bone and lamellar bone. The bone bundle develops directly in connective tissue that has not been calcified. Osteoblasts, which are differentiated from the mesenchyme, secrete an intercellular substance containing collagen fibrils. This osteoid matrix calcifies by precipitating apatite crystals. Primary ossification centers only show minimal bone calcification density. The apatite crystal deposits are mostly irregular and structured like nets that are contained in the medullary and cortical regions. Mineralization occurs very quickly (several tens of thousands of millimeters per day) and can occur simultaneously in large areas. These apatite deposits increase with time. Bone tissue is only considered mature when the crystalized area is arranged in the same direction as collagen fibrils.
Bone tissue is divided into two, called the outer cortical and medullary regions, these two areas are destroyed by the resorption process; which goes along with further bone formation. The surrounding connective tissue will differentiate into the periosteum. The lining in the periosteum is rich in cells, has osteogenic function and contributes to the formation of thick bones as in the endosteum.
In adults, the bundle bone is usually only formed during rapid bone remodeling. This is reinforced by the presence of lamellar bone. Unlike bundle bone formation, lamellar bone development occurs only in mineralized matrix (e.g., cartilage that has calcified or bundle bone spicules). The nets in the bone bundle are filled to strengthen the lamellar bone, until compact bone is formed. Osteoblasts appear in the mineralized matrix, which then form a circle with intercellular matter surrounding the central vessels in several layers (Haversian system). Lamella bone is formed from 0.7 to 1.5 microns per day. The network is formed from complex fiber arrangements, responsible for its mechanical properties. The arrangement of apatites in the concentric layer of fibrils finally meets functional requirements. Lamellar bone depends on ongoing deposition and resorption which can be influenced by environmental factors, one of this which is orthodontic treatment.
Intramembranous bone formation from desmocranium (suture and periosteum) is mediated by mesenchymal skeletogenetic structures and is achieved through bone deposition and resorption [8]. This development is almost entirely controlled through local epigenetic factors and local environmental factors (i.e. by muscle strength, external local pressure, brain, eyes, tongue, nerves, and indirectly by endochondral ossification). Genetic factors only have a nonspecific morphogenetic effect on intramembranous bone formation and only determine external limits and increase the number of growth periods. Anomaly disorder (especially genetically produced) can affect endochondral bone formation, so local epigenetic factors and local environmental factors, including steps of orthodontic therapy, can directly affect intramembranous bone formation [3, 11].
During endochondral ossification, the tissue that will become bone is firstly formed from cartilage, separated from the joint and epiphysis, surrounded by perichondrium which then forms the periosteum [11]. Based on the location of mineralization, it can be divided into: Perichondral Ossification and Endochondral Ossification. Both types of ossification play an essential role in the formation of long bones where only endochondral ossification takes place in short bones. Perichondral ossification begins in the perichondrium. Mesenchymal cells from the tissue differentiate into osteoblasts, which surround bony diaphyseal before endochondral ossification, indirectly affect its direction [3, 8, 12]. Cartilage is transformed into bone is craniofacial bone that forms at the eigth prenatal week. Only bone on the cranial base and part of the skull bone derived from endochondral bone formation. Regarding to differentiate endochondral bone formation from chondrogenesis and intramembranous bone formation, five sequences of bone formation steps were determined [3].
The statements below are the stages of endochondral bone formation (Figure 6) [4, 12]:
Mesenchymal cells group to form a shape template of the future bone.
Mesenchymal cells differentiate into chondrocytes (cartilage cells).
Hypertrophy of chondrocytes and calcified matrix with calcified central cartilage primordium matrix formed. Chondrocytes show hypertrophic changes and calcification from the cartilage matrix continues.
Entry of blood vessels and connective tissue cells. The nutrient artery supplies the perichondrium, breaks through the nutrient foramen at the mid-region and stimulates the osteoprogenitor cells in the perichondrium to produce osteoblasts, which changes the perichondrium to the periosteum and starts the formation of ossification centers.
The periosteum continues its development and the division of cells (chondrocytes) continues as well, thereby increasing matrix production (this helps produce more length of bone).
The perichondrial membrane surrounds the surface and develops new chondroblasts.
Chondroblasts produce growth in width (appositional growth).
Cells at the center of the cartilage lyse (break apart) triggers calcification.
The stage of endochondral ossification. The following stages are: (a) Mesenchymal cells differentiate into chondrocytes. (b) The cartilage model of the future bony skeleton and the perichondrium form. (c) Capillaries penetrate cartilage. Perichondrium transforms into periosteum. Periosteal collar develops. Primary ossification center develops. (d) Cartilage and chondrocytes continue to grow at ends of the bone. (e) Secondary ossification centers develop. (f) Cartilage remains at epiphyseal (growth) plate and at joint surface as articular cartilage.
During endochondral bone formation, mesenchymal tissue firstly differentiates into cartilage tissue. Endochondral bone formation is morphogenetic adaptation (normal organ development) which produces continuous bone in certain areas that are prominently stressed. Therefore, this endochondral bone formation can be found in the bones associated with joint movements and some parts of the skull base. In hypertrophic cartilage cells, the matrix calcifies and the cells undergo degeneration. In cranial synchondrosis, there is proliferation in the formation of bones on both sides of the bone plate, this is distinguished by the formation of long bone epiphyses which only occurs on one side only [2, 14].
As the cartilage grows, capillaries penetrate it. This penetration initiates the transformation of the perichondrium into the bone-producing periosteum. Here, the osteoblasts form a periosteal collar of compact bone around the cartilage of the diaphysis. By the second or third month of fetal life, bone cell development and ossification ramps up and creates the
While these deep changes occur, chondrocytes and cartilage continue to grow at the ends of the bone (the future epiphyses), which increase the bone length and at the same time bone also replaces cartilage in the diaphysis. By the time the fetal skeleton is fully formed, cartilage only remains at the joint surface as articular cartilage and between the diaphysis and epiphysis as the epiphyseal plate, the latter of which is responsible for the longitudinal growth of bones. After birth, this same sequence of events (matrix mineralization, death of chondrocytes, invasion of blood vessels from the periosteum, and seeding with osteogenic cells that become osteoblasts) occur in the epiphyseal regions, and each of these centers of activity is referred to as a
There are four important things about cartilage in endochondral bone formation:
Cartilage has a rigid and firm structure, but not usually calcified nature, giving three basic functions of growth (a) its flexibility can support an appropriate network structure (nose), (b) pressure tolerance in a particular place where compression occurs, (c) the location of growth in conjunction with enlarging bone (synchondrosis of the skull base and condyle cartilage).
Cartilage grows in two adjacent places (by the activity of the chondrogenic membrane) and grows in the tissues (chondrocyte cell division and the addition of its intercellular matrix).
Bone tissue is not the same as cartilage in terms of its tension adaptation and cannot grow directly in areas of high compression because its growth depends on the vascularization of bone formation covering the membrane.
Cartilage growth arises where linear growth is required toward the pressure direction, which allows the bone to lengthen to the area of strength and has not yet grown elsewhere by membrane ossification in conjunction with all periosteal and endosteal surfaces.
Membrane disorders or vascular supply problem of these essential membranes can directly result in bone cell death and ultimately bone damage. Calcified bones are generally hard and relatively inflexible and sensitive to pressure [12].
Cranial synchondrosis (e.g., spheno ethmoidal and spheno occipital growth) and endochondral ossification are further determined by chondrogenesis. Chondrogenesis is mainly influenced by genetic factors, similar to facial mesenchymal growth during initial embryogenesis to the differentiation phase of cartilage and cranial bone tissue.
This process is only slightly affected by local epigenetic and environmental factors. This can explain the fact that the cranial base is more resistant to deformation than desmocranium. Local epigenetic and environmental factors cannot trigger or inhibit the amount of cartilage formation. Both of these have little effect on the shape and direction of endochondral ossification. This has been analyzed especially during mandibular condyle growth.
Local epigenetics and environmental factors only affect the shape and direction of cartilage formation during endochondral ossification Considering the fact that condyle cartilage is a secondary cartilage, it is assumed that local factors provide a greater influence on the growth of mandibular condyle.
Chondrogenesis is the process by which cartilage is formed from condensed mesenchyme tissue, which differentiates into chondrocytes and begins secreting the molecules that form the extracellular matrix [5, 14].
The statement below is five steps of chondrogenesis [8, 14]:
Chondroblasts produce a matrix: the extracellular matrix produced by cartilage cells, which is firm but flexible and capable of providing a rigid support.
Cells become embed in a matrix: when the chondroblast changes to be completely embed in its own matrix material, cartilage cells turn into chondrocytes. The new chondroblasts are distinguished from the membrane surface (perichondrium), this will result in the addition of cartilage size (cartilage can increase in size through apposition growth).
Chondrocytes enlarge, divide and produce a matrix. Cell growth continues and produces a matrix, which causes an increase in the size of cartilage mass from within. Growth that causes size increase from the inside is called interstitial growth.
The matrix remains uncalcified: cartilage matrix is rich of chondroitin sulfate which is associated with non-collagen proteins. Nutrition and metabolic waste are discharged directly through the soft matrix to and from the cell. Therefore, blood vessels aren’t needed in cartilage.
The membrane covers the surface but is not essential: cartilage has a closed membrane vascularization called perichondrium, but cartilage can exist without any of these. This property makes cartilage able to grow and adapt where it needs pressure (in the joints), so that cartilage can receive pressure.
Endochondral ossification begins with characteristic changes in cartilage bone cells (hypertrophic cartilage) and the environment of the intercellular matrix (calcium laying), the formation which is called as primary spongiosa. Blood vessels and mesenchymal tissues then penetrate into this area from the perichondrium. The binding tissue cells then differentiate into osteoblasts and cells. Chondroblasts erode cartilage in a cave-like pattern (cavity). The remnants of mineralized cartilage the central part of laying the lamellar bone layer.
The osteoid layer is deposited on the calcified spicules remaining from the cartilage and then mineralized to form spongiosa bone, with fine reticular structures that resemble nets that possess cartilage fragments between the spicular bones. Spongy bones can turn into compact bones by filling empty cavities. Both endochondral and perichondral bone growth both take place toward epiphyses and joints. In the bone lengthening process during endochondral ossification depends on the growth of epiphyseal cartilage. When the epiphyseal line has been closed, the bone will not increase in length. Unlike bone, cartilage bone growth is based on apposition and interstitial growth. In areas where cartilage bone is covered by bone, various variations of zone characteristics, based on the developmental stages of each individual, can differentiate which then continuously merge with each other during the conversion process. Environmental influences (co: mechanism of orthopedic functional tools) have a strong effect on condylar cartilage because the bone is located more superficially [5].
Cartilage bone height development occurs during the third month of intra uterine life. Cartilage plate extends from the nasal bone capsule posteriorly to the foramen magnum at the base of the skull. It should be noted that cartilages which close to avascular tissue have internal cells obtained from the diffusion process from the outermost layer. This means that the cartilage must be flatter. In the early stages of development, the size of a very small embryo can form a chondroskeleton easily in which the further growth preparation occurs without internal blood supply [1].
During the fourth month in the uterus, the development of vascular elements to various points of the chondrocranium (and other parts of the early cartilage skeleton) becomes an ossification center, where the cartilage changes into an ossification center, and bone forms around the cartilage. Cartilage continues to grow rapidly but it is replaced by bone, resulting in the rapid increase of bone amount. Finally, the old chondrocranium amount will decrease in the area of cartilage and large portions of bone, assumed to be typical in ethmoid, sphenoid, and basioccipital bones. The cartilage growth in relation to skeletal bone is similar as the growth of the limbs [1, 3].
Longitudinal bone growth is accompanied by remodeling which includes appositional growth to thicken the bone. This process consists of bone formation and reabsorption. Bone growth stops around the age of 21 for males and the age of 18 for females when the epiphyses and diaphysis have fused (epiphyseal plate closure).
Normal bone growth is dependent on proper dietary intake of protein, minerals and vitamins. A deficiency of vitamin D prevents calcium absorption from the GI tract resulting in rickets (children) or osteomalacia (adults). Osteoid is produced but calcium salts are not deposited, so bones soften and weaken.
At the length of the long bones, the reinforcement plane appears in the middle and at the end of the bone, finally produces the central axis that is called the diaphysis and the bony cap at the end of the bone is called the epiphysis. Between epiphyses and diaphysis is a calcified area that is not calcified called the epiphyseal plate. Epiphyseal plate of the long bone cartilage is a major center for growth, and in fact, this cartilage is responsible for almost all the long growths of the bones. This is a layer of hyaline cartilage where ossification occurs in immature bones. On the epiphyseal side of the epiphyseal plate, the cartilage is formed. On the diaphyseal side, cartilage is ossified, and the diaphysis then grows in length. The epiphyseal plate is composed of five zones of cells and activity [3, 4].
Near the outer end of each epiphyseal plate is the active zone dividing the cartilage cells. Some of them, pushed toward diaphysis with proliferative activity, develop hypertrophy, secrete an extracellular matrix, and finally the matrix begins to fill with minerals and then is quickly replaced by bone. As long as cartilage cells multiply growth will continue. Finally, toward the end of the normal growth period, the rate of maturation exceeds the proliferation level, the latter of the cartilage is replaced by bone, and the epiphyseal plate disappears. At that time, bone growth is complete, except for surface changes in thickness, which can be produced by the periosteum [4]. Bones continue to grow in length until early adulthood. The lengthening is stopped in the end of adolescence which chondrocytes stop mitosis and plate thins out and replaced by bone, then diaphysis and epiphyses fuse to be one bone (Figure 7). The rate of growth is controlled by hormones. When the chondrocytes in the epiphyseal plate cease their proliferation and bone replaces the cartilage, longitudinal growth stops. All that remains of the epiphyseal plate is the epiphyseal line. Epiphyseal plate closure will occur in 18-year old females or 21-year old males.
Oppositional bone growth and remodeling. The epiphyseal plate is responsible for longitudinal bone growth.
The cartilage found in the epiphyseal gap has a defined hierarchical structure, directly beneath the secondary ossification center of the epiphysis. By close examination of the epiphyseal plate, it appears to be divided into five zones (starting from the epiphysis side) (Figure 8) [4]:
The resting zone: it contains hyaline cartilage with few chondrocytes, which means no morphological changes in the cells.
The proliferative zone: chondrocytes with a higher number of cells divide rapidly and form columns of stacked cells parallel to the long axis of the bone.
The hypertrophic cartilage zone: it contains large chondrocytes with cells increasing in volume and modifying the matrix, effectively elongating bone whose cytoplasm has accumulated glycogen. The resorbed matrix is reduced to thin septa between the chondrocytes.
The calcified cartilage zone: chondrocytes undergo apoptosis, the thin septa of cartilage matrix become calcified.
The ossification zone: endochondral bone tissue appears. Blood capillaries and osteoprogenitor cells (from the periosteum) invade the cavities left by the chondrocytes. The osteoprogenitor cells form osteoblasts, which deposit bone matrix over the three-dimensional calcified cartilage matrix.
Epiphyseal plate growth. Five zones of epiphyseal growth plate includes: 1. resting zone, 2. proliferation zone, 3. hypertrophic cartilage zone, 4. calcified cartilage zone, and 5. ossification zone.
When bones are increasing in length, they are also increasing in diameter; diameter growth can continue even after longitudinal growth stops. This is called appositional growth. The bone is absorbed on the endosteal surface and added to the periosteal surface. Osteoblasts and osteoclasts play an essential role in appositional bone growth where osteoblasts secrete a bone matrix to the external bone surface from diaphysis, while osteoclasts on the diaphysis endosteal surface remove bone from the internal surface of diaphysis. The more bone around the medullary cavity is destroyed, the more yellow marrow moves into empty space and fills space. Osteoclasts resorb the old bone lining the medullary cavity, while osteoblasts through intramembrane ossification produce new bone tissue beneath the periosteum. Periosteum on the bone surface also plays an important role in increasing thickness and in reshaping the external contour. The erosion of old bone along the medullary cavity and new bone deposition under the periosteum not only increases the diameter of the diaphysis but also increases the diameter of the medullary cavity. This process is called modeling (Figure 9) [3, 4, 15].
Appositional bone growth. Bone deposit by osteoblast as bone resorption by osteoclast.
Recent research reported that bone microstructure is also the principle of bone function, which regulates its mechanical function. Bone tissue function influenced by many factors, such as hormones, growth factors, and mechanical loading. The microstructure of bone tissue is distribution and alignment of biological apatite (BAp) crystallites. This is determined by the direction of bone cell behavior, for example cell migration and cell regulation. Ozasa et al. found that artificial control the direction of mesenchymal stem cell (MSCs) migration and osteoblast alignment can reconstruct bone microstructure, which guide an appropriate bone formation during bone remodeling and regeneration [16].
Bone development begins with the replacement of collagenous mesenchymal tissue by bone. Generally, bone is formed by endochondral or intramembranous ossification. Intramembranous ossification is essential in the bone such as skull, facial bones, and pelvis which MSCs directly differentiate to osteoblasts. While, endochondral ossification plays an important role in most bones in the human skeleton, including long, short, and irregular bones, which MSCs firstly experience to condensate and then differentiate into chondrocytes to form the cartilage growth plate and the growth plate is then gradually replaced by new bone tissue [3, 8, 12].
MSC migration and differentiation are two important physiological processes in bone formation. MSCs migration raise as an essential step of bone formation because MSCs initially need to migrate to the bone surface and then contribute in bone formation process, although MSCs differentiation into osteogenic cells is also crucial. MSC migration during bone formation has attracted more attention. Some studies show that MSC migration to the bone surface is crucial for bone formation [17]. Bone marrow and periosteum are the main sources of MSCs that participate in bone formation [18].
In the intramembranous ossification, MSCs undergo proliferation and differentiation along the osteoblastic lineage to form bone directly without first forming cartilage. MSC and preosteoblast migration is involved in this process and are mediated by plentiful factors in vivo and in vitro. MSCs initially differentiate into preosteoblasts which proliferate near the bone surface and secrete ALP. Then they become mature osteoblasts and then form osteocytes which embedded in an extracellular matrix (ECM). Other factors also regulate the intramembranous ossification of MSCs such as Runx2, special AT-rich sequence binding protein 2 (SATB 2), and Osterix as well as pathways, like the wnt/β-catenin pathway and bone morphogenetic protein (BMP) pathway [17, 19].
In the endochondral ossification, MSCs are first condensed to initiate cartilage model formation. The process is mediated by BMPs through phosphorylating and activating receptor SMADs to transduce signals. During condensation, the central part of MSCs differentiates into chondrocytes and secretes cartilage matrix. While, other cells in the periphery, form the perichondrium that continues expressing type I collagen and other important factors, such as proteoglycans and ALP. Chondrocytes undergo rapid proliferation. Chondrocytes in the center become maturation, accompanied with an invasion of hypertrophic cartilage by the vasculature, followed by differentiation of osteoblasts within the perichondrium and marrow cavity. The inner perichondrium cells differentiate into osteoblasts, which secrete bone matrix to form the bone collar after vascularization in the hypertrophic cartilage. Many factors that regulate endochondral ossification are growth factors (GFs), transforming growth factor-β (TGF-β), Sry-related high-mobility group box 9 (Sox9) and Cell-to-cell interaction [17, 19].
Osteogenesis/ossification is the process in which new layers of bone tissue are placed by osteoblasts.
During bone formation, woven bone (haphazard arrangement of collagen fibers) is remodeled into lamellar bones (parallel bundles of collagen in a layer known as lamellae)
Periosteum is a connective tissue layer on the outer surface of the bone; the endosteum is a thin layer (generally only one layer of cell) that coats all the internal surfaces of the bone
Major cell of bone include: osteoblasts (from osteoprogenitor cells, forming osteoid that allow matrix mineralization to occur), osteocytes (from osteoblasts; closed to lacunae and retaining the matrix) and osteoclasts (from hemopoietic lineages; locally erodes matrix during bone formation and remodeling.
The process of bone formation occurs through two basic mechanisms:
Intramembranous bone formation occurs when bone forms inside the mesenchymal membrane. Bone tissue is directly laid on primitive connective tissue referred to mesenchyma without intermediate cartilage involvement. It forms bone of the skull and jaw; especially only occurs during development as well as the fracture repair.
Endochondral bone formation occurs when hyaline cartilage is used as a precursor to bone formation, then bone replaces hyaline cartilage, forms and grows all other bones, occurs during development and throughout life.
During interstitial epiphyseal growth (elongation of the bone), the growth plate with zonal organization of endochondral ossification, allows bone to lengthen without epiphyseal growth plates enlarging zones include:
Zone of resting.
Zone of proliferation.
Zone of hypertrophy.
Zone of calcification.
Zone of ossification and resorption.
During appositional growth, osteoclasts resorb old bone that lines the medullary cavity, while osteoblasts, via intramembranous ossification, produce new bone tissue beneath the periosteum.
Mesenchymal stem cell migration and differentiation are two important physiological processes in bone formation.
The author is grateful to Zahrona Kusuma Dewi for assistance with preparation of the manuscript.
The authors declare that there is no conflict of interests regarding the publication of this paper.
alkaline phosphatase biological apatite bone morphogenetic protein extracellular matrix growth factors mesenchymal stem cells runt-related transcription factor 2 special AT-rich sequence binding protein 2 sry-related high-mobility group box 9 transforming growth factor-β
COVID-19 causative virus (SARS-CoV-2) affects many body organs and systems to induce its pathogenesis. The disease is severe in people with comorbidities such as obesity, diabetes, hypertension, chronic respiratory disease, cerebrovascular disease, and chronic kidney and liver disease [1].
In neural tissues, the mechanism of invasion is well-established. It involves the interaction of ACE2 (Angiotensin-converting enzyme 2) receptors and spike protein. SARS-CoV-2 enters the nervous system via neurotropism, hematological dissemination, vasculotropism, and cytokine storm [2, 3].
Some of the common neurological symptoms of SARS-CoV-2 include CNS symptoms; (dizziness, delirium, confusion, prominent agitation, and dizziness), acute cerebrovascular disease, and epilepsy; PNS symptoms; ageusia (loss of sense of taste), hypogeusia (reduction in the ability to taste), anosmia (inability to smell), hyposmia (reduction in the ability to smell), and neuralgia (painful sensation in the body) and skeletal muscular symptoms: myalgia/fatigue and muscle injury [3, 4].
Many bioactive compounds have been reviewed for their antiviral effects which may have both preventive and curative effects [5]. Mainstay pharmacological/non-pharmacological interventions for prevention, management, and treatment include COVID-19 vaccines, remdesivir [6], SARS-CoV-2 targeting monoclonal antibodies such as Casirivimab and Imdevimab, Immune modulators (Baricitinib), immunosuppressive therapy as well adherence to public health guidelines such as handwashing, use of alcohol gels and face masks, etc.
In this chapter, we highlighted various neurological disorders and symptoms caused by COVID-19 and examined the relationship between the neurological systems and COVID-19. Additionally, we evaluated current therapies including the administration of vaccines, anti-virals, and their prospects for future applications.
The novel coronavirus disease (COVID-19) has been a dire threat to public health, the global economy, and human co-existence since its first report in Wuhan, China in 2019 [7]. Globally, as of 2nd June 2022, there have been 6,293,414 deaths due to COVID-19 out of 528,275,339 confirmed cases. To curtail the menace of COVID-19, 11,947,644,522 vaccine doses have been reported administered globally [8]. Prior to the development and administration of vaccines, a number of preventive measures (hand-washing under running water, use of alcohol-based hand sanitizer, social distancing, wearing of face mask, etc.) were put in place by health regulatory bodies to manage the transmission of the disease [7]. These measures were evaluated to study compliance and effectiveness in curbing the spread of the virus [9, 10, 11]. Although the global incidence and mortality rate has declined, adherence to preventive measures and vaccination is still encouraged.
COVID-19 severity has been reported in elderly patients and those with comorbidities (obesity, diabetes, hypertension, chronic respiratory disease, cardiovascular disease, cerebrovascular disease, chronic kidney, and liver disease) [1, 12]. Due to the novelty of the disease, the possibility of other long-term effects is still unknown. However, those with severe cases of infection can develop acute or chronic effects (graphical abstract) such as chronic fatigue syndrome, complications of the heart, lung, and kidney, neurological defects (loss of taste and smell, delirium, headaches, brain inflammation, stroke, and Guillain-Barre syndrome) [12, 13]. This calls for a need for closer monitoring and more research into the aftermath effect of the COVID-19, even in well-managed patients.
The SARS-CoV-2 respiratory indices are well known and reported. Recently, there has been a significant increase in evidence showing anosmia (complete loss of smell) as a SARS-CoV-2 symptom, indicating a high level of neurological involvement following the infection and also SARS-CoV-2 having neuro-invasive properties. Studies suggest that SARS-CoV-2 enters the central nervous system (CNS) in either of the two ways; through systemic vascular dissemination or across the cribriform plate of the ethmoid bone, which might have consequences concerning anosmia as experienced by the SARS-CoV-2 patients [14]. The virus invades the neural tissue once in the systemic circulation due to its neurotropism properties and then, binds and interacts with ACE2 (Angiotensin-converting enzyme 2) receptors in the endothelium capillary via the spike proteins [14, 15]. Previously, ACE2 has been shown to be expressed in the upper and lower epithelium of the airways together with the CNS endothelial capillary [16]. One of the studies conducted evaluating SARS-CoV-2 spike glycoprotein structural integrity showed an approximately 20- a fold affinity increases to ACE2 when compared to the spike protein of the sister virus SARS-CoV-2 [17]. However, using BLASTp, the spike proteins of the two sister viruses are structurally similar but not identical, explaining the differences in the neurological prevalence. Meanwhile, not all the human cell lines that express ACE2 are susceptible to the novel coronavirus infection. Nevertheless, several neurological manifestations of the SARS-CoV-2 infection should be given absolute attention together with its well-understood respiratory index.
Stroke is now common, developing, and/or potentially devastating SARS-CoV-2 infection complication [18]; about 2–6% of hospitalized COVID-19 patients have developed an acute cerebrovascular event [19]. In 2020, a large vessel stroke was reported in five patients (< 50 years of age) infected with SARS-CoV-2 [20]. Studies on the thromboembolic complications rate in SARS-CoV-2 patients showed 1.6% [21] and 2.5% [22] reported ischemic stroke occurrences. Klok and Lodigiani showed that the thrombotic complications were significantly high for their respective institutions. However, there are other risk factors predisposing COVID-19 patients to thromboembolic stroke development beyond the usual metabolic and cardiovascular co-morbidities. At this moment, various mechanisms of SARS-CoV-2 induced stroke have been reported including myocardial damage with cerebral embolism, coagulopathy, or pre-existing atheroma plaque destabilization [23]. The viral invasion led to thrombosis by activating immune response involving platelets, endothelium, and coagulation. Furthermore, SARS-CoV-2 causes cytokine storms resulting in increased D-dimers, affecting coagulation, and inducing stroke. Also, viral invasion can lead to heart damage, resulting in viral myocarditis and finally cardioembolic stroke. Inflammation can destabilize the fibrous capsule surrounding the atheroma plaque, eventually, exposing the thrombogenic clotting material, initiating arteries clogging and thus, causing a stroke [23].
GBS is an acute acquired autoimmune disorder of the peripheral nerves that occurs as a result of infection [24]. Actually, GBS is symmetrical ascending paralysis, mostly due to bacteria or viral infection of the respiratory or gastrointestinal tract [25]. It is a rare disease of the peripheral nervous system (PNS) with approximately 1.11 in 100,000 incidences annually [26]. Since the COVID-19 outbreak, the number of GBS cases has increased significantly. There have been some confirmed cases and a potential report of GBS as significant SARS-CoV-2 neurological sequelae. Among the eleven cases published in the literature, there is substantial capriciousness in an indication of GBS onset, together with distinctive respiratory distress of SARS-CoV-2 [27]. GBS is related to recent inoculation from a possible range of pathogens, explaining the disease’s clinical heterogeneity [28]. Despite the inconsistency in the symptom onset in relation to COVID-19 diagnosis, it is of note that most reports described constant clinical features of variable sensory abnormalities with deep tendon reflex loss and lower limb weakness over the upper limb. Various mechanisms the virus uses to trigger acute areflexic state in GBS have been reported. Possibly, antibodies against the surface glycoproteins are generated against the pathogen which also responds to the comparable native protein structures located on the neuronal surface leading to GBS clinical features [29]. Another probable mechanism is the macrophage activation syndrome (cytokine storm) and hyper-inflammation might be involved in GBS pathogenesis in SARS-CoV-2 individuals [30].
Individuals with neurocognitive disorders have a high risk of being infected with COVID-19. APOE e4 increases the risk of Alzheimer’s neurocognitive disorder. Previous studies revealed that the deformed blood–brain barrier (BBB) in Alzheimer’s patients predisposes them to infections. Furthermore, memory impairment related to neurocognitive disorders could possibly affect the patient’s capability to observe the COVID-19 preventive measures including the use of masks, hand-sanitizing, and social distancing [31]. Individuals with neurocognitive disorders are more liable to experience comorbidities including diabetes, pneumonia, or cardiovascular disease increasing their risk of severe morbidities or death if they contract COVID-19 [32]. Previous research has found a bidirectional association between viral infections and neurocognitive disorders. Patients with neurocognitive disorders have a higher chance of viral infection and patients with a poor immune response to the infection have a higher risk of neurocognitive disorders [31]. Further research is needed to understand if the molecular and socioeconomic interactions play role in the higher incidence of COVID-19 in patients with neurocognitive disorders patients, and to identify whether SARS-CoV-2 infection accelerates or triggers neurocognitive disorders [31].
COVID-19 could potentially aggravate neurological symptoms in PD individuals [33]. The effect of COVID-19 on individuals with Parkinson’s (PD) disease is multifaceted as SARS-CoV-2 can affect their health directly, with a downstream effect on the advancement of the disease and the quality of life.. Several studies have reported the onset of deteriorating PD and motor symptoms (for example speech disturbance, fall, dystonic spasms) preceding COVID-19 diagnosis [34, 35, 36]. Motor symptom changes might be a result of a decrease in oral therapy absorption due to diarrhea -a COVID-19 symptom [37]. Worsening of the symptoms can be ascribed to the pandemic subordinate effects including changes in normal activities and stress. Fatigue, rigidity, pain, concentration, and tremor were recorded during neurological symptoms evaluation for individuals with PD a month before the pandemic began and beyond [38].
Several COVID-19 patients appeared to have severely low blood oxygen saturation levels [39], leading to hypoxia which causes damage to the tissues [40]. Meanwhile, these patients do not get enough oxygenation via the blood, COVID-19 individuals with hypoxia often do not show much respiratory distress, but they feel alert, and can easily talk [39]. Hence, hypoxia in COVID-19 individuals is often known as “happy” or “silent” hypoxia due to its minimal additional effects [39]. In a study by Mortaz et al. COVID-19 participants’ RBC had higher amounts of intracellular NO (nitric oxide). This is not due to hypoxia per se, but it could provide protection against the hypoxia reported in COVID-19 patients. Constitutive NO generation in RBCs is mostly dependent on NOS during health, although NO production in hypoxic settings may entail nitrite reduction by deoxyhemoglobin carbonic anhydrase and/or eNOS itself. Also, COVID-19 participants’ RBC had higher amounts of intracellular NO [39].
In the past, viruses such as arbovirus, measles virus, enterovirus, herpes simplex virus (HSV), Varicella-Zoster virus (VZV), Cytomegalovirus (CMV), Epstein -Barr virus (EBV), and Human JC virus (JCV) have been reported to invade the nervous systems of hosts with severe neurological effects [41]. Now, SARS CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19 has joined that list with recently reported neurological manifestations of the disease. The mode of entry of these viruses including SARS CoV-2 has been thoroughly studied and classified into the several major routes: endocytosis (direct fusion with neurons), sensory nerve endings, synapses, and axons, circulating leukocytes, lymph nodes, the blood–brain barrier (BBB), the Central Nervous System (CNS) and the Peripheral Nervous System (PNS) [42].
ACE2 has a high affinity for SARS-CoV-2 (Figures 1 and 2).SARS-CoV-2 interacts with ACE2 receptors to invade the cells in the body [45, 46] by receiving the spike (peplomer) glycoprotein of the virus. mRNA expression profile of ACE2 shows that the enzyme is organ-specific but expressed in almost every tissue in the body [46, 47]. ACE2 receptor is usually found in the pulmonary type II alveolar cells and respiratory epithelial at high levels because COVID-19 is primarily a respiratory disease [48, 49]. ACE2 is also found in other body tissues and cells such as myocardial and endothelial cells [50], kidney, stomach, colon, and ileum cells [51], oral mucosa cells [52], astrocytes, neuron and glial cells of the brain and spinal cord tissues (Figure 1) [14].
Distribution of ACE 2 in the human body. (image adapted from [
SARS-CoV life cycle (image adapted from [
The ACE2 gene is located on chromosome Xp22.22 and contains 18 exons and 20 introns [53]. It produces an 805 amino acid, type I transmembrane glycoprotein which contains a 17-amino-acid N-terminal signal peptide and a 22-amino acid C-terminal membrane hydrophobic transmembrane region anchoring it in the cell membrane [46]. It also has a HEXXH zinc-binding metalloprotease motif, a C-terminal collecting domain, and an insulin-like domain [53]. ACE2 gene expression is also found in other respiratory disorders such as SARS, Middle East respiratory syndrome (MERS), and H1N1 influenza [54].
SARS-CoV-2 directly attacks neural cells and infects cerebrovascular endothelium and brain parenchyma (medial temporal lobe) causing early apoptosis and necrosis (Figure 3) [4, 44, 48]. This attack occurs through a series of mechanisms such as proteolysis, viral fusion with membrane, and entry mediated by ACE2 and transmembrane serine protease 2 (TMPRSS2) in some parts of the brain, CNS, PNS, and cerebrospinal fluid described through animal studies [see 55, 56, 57, 58 for more details].
Neurotropism of SARS-CoV-2. SARS-CoV-2 (image and description text and Servier medical art,
Scheme illustration of the neurotropism, neuroinflammatory processes, and effects on brain cells triggered by COVID-19 in patients. Image and description text adapted from [
Spike (S) proteins bind the angiotensin-converting enzyme 2 (ACE-2) receptor of the target cell. Cleavage of the S protein by type II transmembrane serine protease (TMPRSS2), facilitates viral entry. ACE-2 mRNA expression and double-positive ACE-2 + TMPRSS2 + cells have been identified, among others, on neurons and glial cells, in the cerebral cortex, striatum, hypothalamus, substantia nigra, and brain stem, making the CNS potential direct targets of SARS-CoV-2 infection.
Immune cells from the periphery and the central nervous system (CNS) (A) Produce effector molecules that include pro-inflammatory cytokines and autoantibodies. (B) SARS-CoV-2 infection also causes leakage of the blood–brain barrier leading in some cases to hemorrhage and cerebral infarct, as well as eliciting leukocyte infiltration. (C) In the parenchyma, the CNS cells become infected by SARS-CoV via angiotensin-converting enzyme 2 (ACE2) endocytosis mediated by the two-pore channel 2 (TCP2). (D) SARS-CoV-2 infection leads to loss of physiological functions of the brain cells, including neurons, astrocytes, microglia, and oligodendrocytes. Cell types are identified in the following manner; A, Astrocyte; L, Leukocyte; M, Microglia; N, Neurone; O, Oligodendrocyte.
Several case reports of SARS-CoV-2 from hospitals, clinical settings, and study groups indicate different manifestations of neurological symptoms and effects [43, 60]. These studies report these common neurological manifestations to occur in the brain, olfactory areas, and central nervous system. A report from the treatment of a COVID-19 patient carried out by [61] described encephalitis (inflammation of the brain) detected through CT scans as a clinical manifestation of SARS-CoV-2 infection. One study in China. Another study in the UK reported that patients developed unexplained encephalopathic features (detected through MRI) and showed a cognitive decline [62]. Additionally, an autopsy of human brain samples from neurologically diseased patients showed the presence of the virus in the cortical neurons of the brain [55, 63]. This presence is attributed to inter-neuronal propagation and axonal transport of the virus into the CNS. These reports constitute evidence that SARS-CoV-2 has neuro-invasive potential. It also stresses the need for further research to ascertain the level of damage it can cause in neurological systems as the exact mechanism of invasion is still unclear.
Similarly, clinical manifestations such as stroke, acute necrotizing hemorrhagic encephalopathy, acute Guillain–Barré syndrome, and meningitis usually accompany the neurological effects of COVID-19. But they are frequent in individuals who are critically ill, adults who are old, and people who have suffered from previous infections of embolism or cardiovascular diseases [20, 65, 66].
Numerous probable therapies for COVID-19 are being studied and tested, but, fortuitously, some medications have been approved by the FDA and made available for infected individuals [6]. Some pharmaceutical medications are being evaluated as possible therapies with different degrees of success [67]. Hydroxychloroquine, an antimalarial and anti-inflammatory drug, was first suggested to have potential against COVID-19 [6], but was later shown to be ineffective [68]; Ribavirin inhibits viral fusion and entry into host cells [6]. The use of Remdesivir for COVID-19 treatment prevented SARS-CoV-2 replication, while tocilizumab, an antagonist drug, also prevents the virus entry into the host cells [6].
ATN-161 has been shown to affect as an anti-cancer and ischemic stroke agent and has successfully completed phase I clinical trial for cancer showing to be well-tolerated without any toxicity. In an ischemic stroke study, increased expression of α5β1 integrin in post-stroke brain endothelial cells was linked to BB breakdown and then increased neuroinflammation and edema. These conditions can be inhibited by ATN-161 [471]. ATN-161 has been shown to be a potential antiviral therapy following a study that reported ATN-161 blocking viral replication of the beta-coronavirus porcine hemagglutinating encephalomyelitis virus (PHEV) in mice through the α5β1-FAK signaling mechanism [69]. In the study, it was found that SARS-CoV-2 spike protein was attached to α5β1 and α5β1/hACE2 which was inhibited by ATN-161 in VeroE6 cells in vitro. This study, therefore, recommends further studies on the ATN-161 as a possible COVID-19 therapy against COVID-19 related neurological disorders. The last possibility for a possible treatment is convalescent plasma, in which the infected individual receives plasma from a recovered COVID-19 individual. This was done in optimisms that the antibodies in the plasma of the improved individuals could help fight the virus in infected ones [67].
Managing prior neurological diseases such as stroke might remain similar to the pre-COVID-19 era. Continuing immunomodulation should continue as well as constant for drug-related adverse effects observation, since withdrawal may initiate a reversion [70]. Individuals involved must consciously observe hand hygiene and social distancing to avoid being infected with SARS CoV-2 [71, 72].
The COVID-19 pandemic has impacted our lives beyond health. Today, we have learned new ways of dealing with a pandemic and our understanding of viruses has expanded to newer dimensions. In this chapter, we reviewed the specific effects of COVID-19 on the neurological system and the various symptoms in the CNS, PNS, and skeletomuscular systems. Studies done so far emphasize the need for further research to ascertain the level of damage SARS-CoV-2 can cause in neurological systems as the exact mechanism of invasion remains unclear. Once clearly defined, existing drugs can be repurposed, new pharmacological interventions can be developed, and combination therapies can be designed to relieve neurological symptoms and the effects of SARS-CoV-2 on neurological systems.
The authors declare no conflict of interest.
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The Gram-positive pathogen is armed with battery of virulence factors that facilitate to establish infections in the hosts. The organism is well known for its ability to acquire resistance to various antibiotic classes. The emergence and spread of methicillin-resistant S. aureus (MRSA) strains which are often multi-drug resistant in hospitals and subsequently in community resulted in significant mortality and morbidity. The epidemiology of MRSA has been evolving since its initial outbreak which necessitates a comprehensive medical approach to tackle this pathogen. Vancomycin has been the drug of choice for years but its utility was challenged by the emergence of resistance. In the last 10 years or so, newer anti-MRSA antibiotics were approved for clinical use. However, being notorious for developing antibiotic resistance, there is a continuous need for exploring novel anti-MRSA agents from various sources including plants and evaluation of non-antibiotic approaches.",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Arumugam Gnanamani, Periasamy Hariharan and Maneesh Paul-\nSatyaseela",authors:[{id:"192829",title:"Dr.",name:"Arumugam",middleName:null,surname:"Gnanamani",slug:"arumugam-gnanamani",fullName:"Arumugam Gnanamani"},{id:"204388",title:"Dr.",name:"Periasamy",middleName:null,surname:"Hariharan",slug:"periasamy-hariharan",fullName:"Periasamy Hariharan"},{id:"204389",title:"Dr.",name:"Maneesh",middleName:null,surname:"Paul-Satyaseela",slug:"maneesh-paul-satyaseela",fullName:"Maneesh Paul-Satyaseela"}]},{id:"32282",doi:"10.5772/33983",title:"Bacteriophages of Ralstonia solanacearum: Their Diversity and Utilization as Biocontrol Agents in Agriculture",slug:"bacteriophages-of-ralstonia-solanacearum-their-diversity-and-utilization-as-biocontrol-agents-in-agr",totalDownloads:3748,totalCrossrefCites:7,totalDimensionsCites:23,abstract:null,book:{id:"555",slug:"bacteriophages",title:"Bacteriophages",fullTitle:"Bacteriophages"},signatures:"Takashi Yamada",authors:[{id:"98151",title:"Dr.",name:"Takashi",middleName:null,surname:"Yamada",slug:"takashi-yamada",fullName:"Takashi Yamada"}]},{id:"32276",doi:"10.5772/34642",title:"Bacteriophages and Their Structural Organisation",slug:"bacteriophages-and-their-structural-organisation-",totalDownloads:12411,totalCrossrefCites:9,totalDimensionsCites:17,abstract:null,book:{id:"555",slug:"bacteriophages",title:"Bacteriophages",fullTitle:"Bacteriophages"},signatures:"E.V. Orlova",authors:[{id:"101052",title:"Prof.",name:"Elena",middleName:null,surname:"Orlova",slug:"elena-orlova",fullName:"Elena Orlova"}]},{id:"53782",doi:"10.5772/66645",title:"Methicillin-Resistant Staphylococcus aureus (MRSA) in Food- Producing and Companion Animals and Food Products",slug:"methicillin-resistant-staphylococcus-aureus-mrsa-in-food-producing-and-companion-animals-and-food-pr",totalDownloads:2743,totalCrossrefCites:8,totalDimensionsCites:16,abstract:"Methicillin-resistant Staphylococcus aureus (MRSA) has become a growing concern in companion and food-producing animals. The presence of multidrug-resistance with a wide range of extracellular enterotoxin genes, virulence factors, and Panton-Valentine leukocidin (pvl) cytotoxin genes confer life-threatening traits on MRSA and makes them highly pathogenic and difficult to treat. Clonal complex 398 (CC398), a predominant clonal lineage of livestock-associated-MRSA in domestic animals and retail meat, is capable of infecting humans. In order to monitor and prevent MRSA contamination, it is critical to understand its source and transmission dynamics. In this review, we describe MRSA in food-producing animals (pig, cattle, chicken), horses, pet animals (dogs, cats), and food products (pork, beef, chicken, milk, and fish).",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Jungwhan Chon, Kidon Sung and Saeed Khan",authors:[{id:"189634",title:"Dr.",name:"Kidon",middleName:null,surname:"Sung",slug:"kidon-sung",fullName:"Kidon Sung"},{id:"190400",title:"Dr.",name:"Jungwhan",middleName:null,surname:"Chon",slug:"jungwhan-chon",fullName:"Jungwhan Chon"},{id:"190401",title:"Dr.",name:"Saeed",middleName:null,surname:"Khan",slug:"saeed-khan",fullName:"Saeed Khan"}]}],mostDownloadedChaptersLast30Days:[{id:"69731",title:"Isolation and Purification of Sulfate-Reducing Bacteria",slug:"isolation-and-purification-of-sulfate-reducing-bacteria",totalDownloads:1526,totalCrossrefCites:1,totalDimensionsCites:6,abstract:"Sulfate-reducing bacteria (SRB) are a widespread group of microorganisms that are often isolated from the anoxygenic environments (lake depths, soil, or swamps), and they are also present in the human and animal intestines. This group is often detected in patients with inflammatory bowel disease, including ulcerative colitis. That is why new rapid methods for their isolation, purification, and identification are important and necessary. In this chapter, the methods of mesophilic SRB isolation from various environments are described. Particular attention is paid to the purification of mesophilic SRB since they can be in close interaction with other microorganisms (Clostridium, Bacteroides, Pseudomonas, etc.), which are their frequent satellites. Moreover, the main methods of mesophilic SRB identification based on their morphological, physiological, biochemical, and genetical characteristics are presented.",book:{id:"8997",slug:"microorganisms",title:"Microorganisms",fullTitle:"Microorganisms"},signatures:"Ivan Kushkevych",authors:[{id:"252191",title:"Associate Prof.",name:"Ivan",middleName:null,surname:"Kushkevych",slug:"ivan-kushkevych",fullName:"Ivan Kushkevych"}]},{id:"65773",title:"Life Cycle of Trypanosoma cruzi in the Invertebrate and the Vertebrate Hosts",slug:"life-cycle-of-em-trypanosoma-cruzi-em-in-the-invertebrate-and-the-vertebrate-hosts",totalDownloads:1450,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"Trypanosoma cruzi (T. cruzi) is a protozoan parasite that causes Chagas disease, a zoonotic disease that can be transmitted to humans by blood-sucking triatomine bugs. T. cruzi is a single-celled eukaryote with a complex life cycle alternating between reduviid bug invertebrate vectors and vertebrate hosts. This article will look at the developmental stages of T. cruzi in the invertebrate vector and the vertebrate hosts, the different surface membrane proteins involved in different life cycle stages of T. cruzi, roles of different amino acids in the life cycle, carbon and energy sources and gene expression in the life cycle of T. cruzi. The author will also look at extracellular vesicles (EV) and its role in the dissemination and survival of T. cruzi in mammalian host.",book:{id:"8806",slug:"biology-of-em-trypanosoma-cruzi-em-",title:"Biology of Trypanosoma cruzi",fullTitle:"Biology of Trypanosoma cruzi"},signatures:"Kenechukwu C. Onyekwelu",authors:[{id:"245368",title:"Dr.",name:"Kenechukwu C.",middleName:null,surname:"Onyekwelu",slug:"kenechukwu-c.-onyekwelu",fullName:"Kenechukwu C. Onyekwelu"}]},{id:"54154",title:"Staphylococcus aureus: Overview of Bacteriology, Clinical Diseases, Epidemiology, Antibiotic Resistance and Therapeutic Approach",slug:"staphylococcus-aureus-overview-of-bacteriology-clinical-diseases-epidemiology-antibiotic-resistance-",totalDownloads:7155,totalCrossrefCites:14,totalDimensionsCites:25,abstract:"Staphylococcus aureus is an important human pathogen that causes wide range of infectious conditions both in nosocomial and community settings. The Gram-positive pathogen is armed with battery of virulence factors that facilitate to establish infections in the hosts. The organism is well known for its ability to acquire resistance to various antibiotic classes. The emergence and spread of methicillin-resistant S. aureus (MRSA) strains which are often multi-drug resistant in hospitals and subsequently in community resulted in significant mortality and morbidity. The epidemiology of MRSA has been evolving since its initial outbreak which necessitates a comprehensive medical approach to tackle this pathogen. Vancomycin has been the drug of choice for years but its utility was challenged by the emergence of resistance. In the last 10 years or so, newer anti-MRSA antibiotics were approved for clinical use. However, being notorious for developing antibiotic resistance, there is a continuous need for exploring novel anti-MRSA agents from various sources including plants and evaluation of non-antibiotic approaches.",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Arumugam Gnanamani, Periasamy Hariharan and Maneesh Paul-\nSatyaseela",authors:[{id:"192829",title:"Dr.",name:"Arumugam",middleName:null,surname:"Gnanamani",slug:"arumugam-gnanamani",fullName:"Arumugam Gnanamani"},{id:"204388",title:"Dr.",name:"Periasamy",middleName:null,surname:"Hariharan",slug:"periasamy-hariharan",fullName:"Periasamy Hariharan"},{id:"204389",title:"Dr.",name:"Maneesh",middleName:null,surname:"Paul-Satyaseela",slug:"maneesh-paul-satyaseela",fullName:"Maneesh Paul-Satyaseela"}]},{id:"55437",title:"Biological Control of Parasites",slug:"biological-control-of-parasites-2017-07",totalDownloads:4281,totalCrossrefCites:7,totalDimensionsCites:7,abstract:"Parasites (ectoparasites or endoparasites) are a major cause of diseases in man, his livestock and crops, leading to poor yield and great economic loss. To overcome some of the major limitations of chemical control methods such as rising resistance, environmental and health risks, and the adverse effect on non‐target organisms, biological control (biocontrol) is now at the forefront of parasite (pests) control. Biocontrol is now a core component of the integrated pest management. Biocontrol is defined as “the study and uses of parasites, predators and pathogens for the regulation of host (pest) densities”. Considerable successes have been achieved in the implementation of biocontrol strategies in the past. This chapter presents a review of the history of biocontrol, its advantages and disadvantages; the different types of biological control agents (BCAs) including predators, parasites (parasitoids) and pathogens (fungi, bacteria, viruses and virus‐like particles, protozoa and nematodes); the effect of biocontrol on native biodiversity; a few case studies of the successful implementation of biocontrol methods and the challenges encountered with the implementation of biocontrol and future perspectives.",book:{id:"5527",slug:"natural-remedies-in-the-fight-against-parasites",title:"Natural Remedies in the Fight Against Parasites",fullTitle:"Natural Remedies in the Fight Against Parasites"},signatures:"Tebit Emmanuel Kwenti",authors:[{id:"191763",title:"Dr.",name:"Tebit Emmanuel",middleName:null,surname:"Kwenti",slug:"tebit-emmanuel-kwenti",fullName:"Tebit Emmanuel Kwenti"}]},{id:"70336",title:"Plastics Polymers Degradation by Fungi",slug:"plastics-polymers-degradation-by-fungi",totalDownloads:1416,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"The studies on plastic degradation are very important for the development of biodegradable plastics, and for reduction of pollution, since plastic waste can remain in the environment for decades or centuries. We have showed the degradation of oxo-biodegradable plastic bags and green polyethylene by Pleurotus ostreatus. This fungus can also produce mushrooms using these plastics. The plastic degradation was possibly by three reasons: (a) presence of pro-oxidant ions or plant polymer, (b) low specificity of the lignocellulolytic enzymes, and (c) the presence of endomycotic nitrogen-fixing microorganisms. In this chapter, the plastic bags’ degradation by abiotic and microbial process using the exposure to sunlight and the use of a white-rot fungus will described. The physical, chemical, and biological alterations of plastic were analyzed after each process of degradation. 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He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. 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Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. 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His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}]},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",slug:"current-topics-in-neglected-tropical-diseases",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Alfonso J. Rodriguez-Morales",hash:"61c627da05b2ace83056d11357bdf361",volumeInSeries:3,fullTitle:"Current Topics in Neglected Tropical Diseases",editors:[{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. 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