\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 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:"925",leadTitle:null,fullTitle:"Mass Transfer - Advanced Aspects",title:"Mass Transfer",subtitle:"Advanced Aspects",reviewType:"peer-reviewed",abstract:"Our knowledge of mass transfer processes has been extended and applied to various fields of science and engineering including industrial and manufacturing processes in recent years. Since mass transfer is a primordial phenomenon, it plays a key role in the scientific researches and fields of mechanical, energy, environmental, materials, bio, and chemical engineering. In this book, energetic authors provide present advances in scientific findings and technologies, and develop new theoretical models concerning mass transfer. This book brings valuable references for researchers and engineers working in the variety of mass transfer sciences and related fields. Since the constitutive topics cover the advances in broad research areas, the topics will be mutually stimulus and informative to the researchers and engineers in different areas.",isbn:null,printIsbn:"978-953-307-636-2",pdfIsbn:"978-953-51-4410-6",doi:"10.5772/1432",price:169,priceEur:185,priceUsd:219,slug:"mass-transfer-advanced-aspects",numberOfPages:838,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"1025f8fc1d2c7a4769cca9205cfac6ae",bookSignature:"Hironori Nakajima",publishedDate:"November 4th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/925.jpg",numberOfDownloads:148333,numberOfWosCitations:186,numberOfCrossrefCitations:95,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:264,numberOfDimensionsCitationsByBook:4,hasAltmetrics:1,numberOfTotalCitations:545,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 4th 2010",dateEndSecondStepPublish:"December 2nd 2010",dateEndThirdStepPublish:"April 8th 2011",dateEndFourthStepPublish:"May 8th 2011",dateEndFifthStepPublish:"July 7th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7,8",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"45206",title:"Dr.",name:"Hironori",middleName:null,surname:"Nakajima",slug:"hironori-nakajima",fullName:"Hironori Nakajima",profilePictureURL:"https://mts.intechopen.com/storage/users/45206/images/1868_n.jpg",biography:"Hironori Nakajima received his B.S. degree in Engineering Science, and M.S. and Ph.D. degrees in Energy Science from Kyoto University. 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Further studies showed that 92% of the population variance is due to genetic factors, and only a fraction of AS genetics can be explained by the influence of HLA-B27. Updated information on the genomic and auto-immune knowledge on AS is an important component of this book, calling attention to markers of disease activity, possible pathways, and the interaction with the gut microbiome, which are a step forward in the knowledge of the pathophysiology of AS, providing markers which are targets for the more recent biologic therapies.
\r\n\tAn update on clinical manifestations, their assessment, monitoring, and imagiology, including peripheral arthritis, enthesopathy, and extra-articular findings, and, the differential diagnosis with other diseases which evolves with axial and peripheral calcifications will be provided.
\r\n\t
\r\n\tAn important component of this book must be dedicated to the more recent treatments namely with biologic therapies but focusing also on new small molecule inhibitors and experimental therapies.
The current trend in medicine is focused on two aspects of healing: on preventive medicine, preventing disease when possible and regenerative medicine, regenerating fractured cells [1]. The methods of treating burn wounds and chronic wounds have changed over the last decades [2]. Early removal of the dead necrosis and closing the wound with an autologous skin transplant of medium thickness (STSG) is still the basis of wound treatment [3], yet new methods that could provide a better esthetic effect continue to be sought after. This change follows a growing consciousness of the patients and the resulting growing demand for new methods of wound treatment and scar healing.
Cellular therapies used to return the patient to the stage of skin completeness are an attractive area of translational medicine [4]. One should remember, however, that cell transplants (autologous keratinocytes or stem cells) were qualified as a healing product for advanced therapy by the Commission for Advanced Therapies of the European Medicines’ Agency (EMEA). Their manufacturing is thus, with all consequences, regulated by the rules of Good Practice [5, 6, 7, 8]. Cultivated skin cells and products obtained by bioengineering means are used in treating patients with both genetic and acquired skin diseases [4]. They are especially useful in the treatment of traumas of chronic surface or depth, such as burns [9]. One of the methods is the delivery of cultured cells to the bed of the wound [10] by, among others, applying autologous cultured cells or skin substitutes obtained by cellular bioengineering [11]. The transplantation of keratinocytes is achieved thanks for obtaining large amounts of cultured cells from a skin biopsy in 3–4 weeks [12]. One of the benefits of using stem cells is their ability to migrate and differentiate the endothelium [13], which promotes revascularization [14]. The increased optimization of microvascular activity is the result of the injection of stem cells into a protracted wound [13]. What is more, the application of cells affects local cellular response, which plays an important role in the rebuilding of skin integrity in the infected wound [15]. It has been proven that stem cells from adipose tissue rebuild skin layering [7]. In our clinic, a positive result was obtained in all the cases of injecting stem cells from adipose tissue into the wound bed [16] (20 patients). There is a thesis that the transplant of allogeneic cells of the amnion can be more effective in the treatment of chronic wounds than autologous stem cells from adipose tissue or bone marrow [17]. Skin epidermis transplants with amniocytes act in an almost physiological way, which suggests that in the stimulation of the stratification of keratinocytes, fibroblasts can be replaced [18]. Fibroblasts seeded over the amnion show good adherence and longevity [19]. This type of wound dressing is suggested for chronic wounds and burn wounds [19, 20]. Alternatively, seeding the keratinocytes over the allogeneic, acellular amnion stimulates their proliferation. The life span of seeded cells is up to 4 weeks [20]. Experience shows that stem cells of the amnion shorten the time of wound healing by twofold. The culturing of keratinocytes was implemented in the Center in 2008. Since then, about 200 cellular transplants have been effectuated in patients with burn wounds, mostly thermal wounds. About 75% of the patients where qualified for the culturing (Figure 1). The size of the wound was 40–79% total body surface area (TBSA) in more than half of the patients who were subject to a cellular transplant. According to Sood et al., the average life of patients subject to the cultured epidermal autografts (CEA) transplant is 91%, while we obtained 88%. It is worth remembering that when it comes to cells of the epidermis, key is the right matching of the patients as leading complications are dermal blisters, itchiness and the loss of the cellular transplant. A common and chronic after-effect is the occurrence of swollen scars [21]. One solution seems to be the use of stem cells [22] which help reduce the scarring [23]. The cells of the epidermis help the heeling of wounds to the maximum depth of IIb. Mansilla et al. and Rasulov et al. suggest the use of stem cells for wounds of great depth [24, 25].
The right choice of the research field for the sourcing of autologous skin for culturing (1) is often problematic due to the limited amount of available research fields (2). The culturing of the epidermis for the transplant (3) and wound before the transplant (4). The source material for the isolation of stem cells (5), stem cell culture (6), the transplant (7) and the final result (8).
RenovaCare is now performing clinical trials of the SkinGun™, which is to distribute stem cells as a suspension (fog) into the wound bed. The isolation, processing and application of the autologous cells takes only 90 min. The inventors of the gun have obtained an award for the patent and assure users that the vitality of the obtained stem cells is up to 97.3% [26]. HARVEST TERUMOBCT used the The Harvest® AdiPrep® system, allowing to obtain a suspension of cells (containing mesenchymal stem cells) in 4 minutes. The singular platform produced by this company allows to transform the platelet rich leukocyte concentrate of bone marrow and fatty tissue into stem cells with the concentration of 160,000/ml and vitality from 78 to 95% [27]. Cytori Therapeutics, Inc. also proposes a device for autologous cell therapy using fractions of cells sourced from fatty tissue (ADRCs). Adipose tissue is a good source of stem cells, but the sine qua non condition for the use of The Celution® System is the minimal amount of fatty tissue of 200 g. In our experience, the whole sourcing and transformation process takes about 2.5 h even though Fraser and associates cites 1.5 h [28], the equivalent of the transformation of the framework in our device. Our Center uses this system as liposuction is a noninvasive procedure while the amount of sourced stem cells and regenerative cells does not require a long cell culturing process. The vitality of cells obtained using the The Celution® System is 93% and is higher than that coming from the PNC’s Multi Station (a manual device), the CHA Biotech Cha-Station and the Medi-Khan’s Lipokit from MaxStem [29]. In our Center, this system is used for the treatment of chronic wounds as it allows for the operation to be performed on the day of admission which shortens the patient’s hospitalization time and allows for the assurance of enough hospital beds to meet the needs of the other burn patients. Subjects included for this procedure contained patients who did not properly responded to CEA therapy and those with non-healing wounds. The procedure of applying ADRC cells sourced from The Celution® System was performed since 2011 in 20 patients (aged 18–80 years old). Good clinic results (final wounds closure) were obtained, which is a huge success preceded by the many months of non-responsive to healing wounds before the procedure (Figure 2).
The isolation and application of regenerative cells from fatty tissue: liposuction (1), the sourced lipoaspirate (2), wound bed injection combined with a grated autologous skin cell transplant (3), the healing of the wound 7 days after the procedure (4), the final effect: a functioning, intact limb (5).
The biggest limitation of the commercially available systems of sourcing stem cells for transplants is the amount of obtained cells, which is why burn patients qualify for stem cells cultured in a Stem Cell Bank. This is most effective from the point of view of a therapeutic success, yet much more complicated from the legal and financial point of view. It requires the production of stem cells in accordance with pharmaceutical law in Clean Rooms. Our Center has carried out a transplant of amniotic stem cells in a hospital exclusion which requires an extra permission from the bioethical commission and the signing of a conscious consent from the recipient. A 30-year-old patient with a thermal wound of 36% IIb/III got the cells in the fourth day after the burn. In 12 days, the wounds healed to a very good esthetic effect. It was said that the legal regulations prevent the procedure from being routinely used. To sum, the good effects of cellular engineering in the last 30 years have been achieved in field of treatment of chronic wounds, such the diabetic foot and venous ulcers as well as deep wounds [30, 31]. It seems they will become a canonical medical practice. The only question is the right choice of therapy methods for the given patient.
The preparation which is an optimal alternative for traditional treatment methods is a transplant of allogeneic, biostatic amniotic tissue [19]. Amniotic tissue is a thin, half-permeable tissue which constitutes the most inner layer of the amnion and is obtained from seronegative donors during pre-planned Cesarean sections. Histologically, the amnion is a five-layer membrane from 0.02 to 0.5 mm thick. Amniotic membrane transplants are undertaken in sterile environments and undergo a final radiative sterilization [20]. The clinical reason for amniotic membrane transplants stems from its natural properties, such as
it being non-immunogenic, mainly an effect of the expression of HLA-G genes in the placenta and amniotic liquid, which are responsible for the immune response during the pregnancy [34],
reducing the risk of infection; it has been proven that the aqueous solution of the amniotic membrane promotes the apoptosis of monocells, such as lymphocytes and macrophages. [35]. This effect is proven by the latest research of Alikarami et al., which have proven the limiting effect of mesoenchymal amniotic liquid cells on the proliferation of mitogenically active T lymphocytes in the
its anti-inflammatory properties; the antibacterial effect observed during the application of the amniotic membrane in the process of wound healing is a common and documented phenomenon. The antibacterial effect is thought to be due to the presence of lysozyme and progesterone in the amniotic liquid as well as the very exact link between the dressing and the wound. Lysozyme is a protein with the properties of a hydrolytic enzyme which breaks down the peptidoglycan present in the cell wall of the bacteria. Progesterone is bacteriostatic against many Gram (+) bacteria [32, 33, 37, 38],
as well as modulating the stroma of the wound; the stromal matrix amnion is rich in extracellular matrix content, such as hyaluronic acid from the embryon, glicosaminoglicanos, various types of collagen and growth factors which promote and modulate the regenerative processes occurring in the wound [39],
stimulating proliferation processes; due to the rich ECM content. The amniotic membrane of the amnion included laminin, fibronectin, collagen IV, V and VII, as well as growth factors such as TGF, which greatly facilitates the adhesion and anchoring of the endothelial cells in the stroma and their proliferation [39, 40],
minimizing pain; the painkiller effect is due to the very close link between the amniotic membrane and the wound, thanks to which the exposed, irritated nerve endings are protected [19, 33].
The clinical scope of the use of the amniotic membrane may include its application as a skin substitute on facial burn wounds, hand burn wounds, on donor areas and granulating wounds. An alternative is the STSG wound dressing of high gradation. Amniotic membrane transplants are useful also in the treatment of autoimmune diseases, for example, the Lyell’s disease [18, 19]. The amniotic membrane can be used together with biological wound dressings, such as allogeneic skin [12, 20]. Properly aseptically prepared biovital transplants such as allogeneic transplants of the amniotic membrane are of high interest today. Good results of intravital transplants of the amniotic membrane in the treatment of wounds can result from the physiological functions of secretion of the amnion cells [41].
The Dr Stanisław Sakiel Centre for Burn Treatment in Siemianowice Śląskie, we began the undertaking of biostatic transplants of the amniotic membrane in 2011. The transplants are produced in the Clean Rooms of the Cell Bank in accordance with the Good Manufacturing Practice (GMP) (Figure 3). From August 2011 to March 2017, 245,229 cm2 transplant cells have been produced. 513 patients have been served by a total of 235,317 cm2, including 9 patients with the Lyell’s Syndrome (Figure 4).
Select stages of production of allogeneic, biostatic transplants of human amnion: (1) the amniotic membrane in a transportation container; (2) rinsing; (3) cutting uneven fragments, measuring the surface; (4) a packaged transplant before sterilization by radiation.
The clinical effect of the therapy of Lyell’s effect in days: 0, 5 and 15.
The obtained evidence and clinical observation suggest a conclusion that the amniotic membrane is an optimal skin substitute in the treatment of shallow burn wounds, specifically facial burn wounds.
Allogeneic skin, obtained mainly from dead, and rarely from living donors, has the properties of an ideal wound dressing: it protects the wound, stimulates healing and reduces pain. This is why is so successful in treating skin diseases such as Stevens-Johnson’s disease and Lyell’s disease [22]. Allogeneic skin is also used for the treatment of topical burn wounds and deep wounds alike, especially when there is not enough of the patient’s skin available to dress their wound [43, 44]. One of its biggest advantages is the ease of gathering it, the possibility of gathering enough for a huge grafting surface, its low toxicity, the ease of keeping it and the relative ease of application [45]. In the case of both widespread and deep wounds, allogeneic skin used to dress a surgically cleaned wound prevents the skin from loosing water, electrolytes and proteins, while at the same time preventing the dehydration of other cells. Moreover, by being a barrier against environmental stimuli, it reduces the proliferation of microorganisms [46]. Thanks to a lowered heat loss experienced by the wound, the hypermetabolic response of the skin to the burn wound diminishes. In wounds suffered by all the layers of skin and thus lacking regenerative potential, an allogeneic skin transplant stimulates the granulation process and wound epithelization, thus creating a stroma for further surgical intervention [47]. The allogeneic skin is also a good biological dressing, which is effective in the treatment of burn wounds of medium depth, covering the epidermis and the dermis. The allogen initiates the growth of blood vessels in the wound bed and stimulates revascularization. While closely adhering to the stroma, it minimizes the level of pain and reduces the amount of necessary dressing changes, allowing for the process of the recreating of the epidermis to continue while the allogen disassociates itself from it without violating the emerging epidermis [48]. In certain cases, allogeneic skin serves as a dressing of wounds previously covered by mesh transplants of autologous skin, allowing to minimize metabolic stress and prevent infections within the wound and creating scaffolding for in vitro cultured keratinocytes [42]. In the Center of Wound Treatment in Siemianowice Slaskie, allogeneic skin is the standard operating procedure for patients with severe wounds, allowing for the temporary dressing and protection of wounds [49]. Moreover, it is also used when the exact depth of the wound cannot be determined while a risk of the wound deepening and the loss of the entire autologous transplant exists [50]. In our clinic, allogeneic skin is used also for the treatment of wounds of medium depth as a dressing meant for the stimulation of granulation tissue and the final closing of the wound thanks to its initiation of the epithelization process [51]. Allogeneic skin was first included in preparations in 2009 while the first transplant was executed in early 2010. At first, it was sourced from multiple organs. Due to clinical demand, from 2014 skin from Departments of Forensic Medicine is being used. Skin sourced in the latter way carries the risk of infected material increased by 58%, with the most common pathogen being
The allogeneic, biostatic transplant (1 and 2), the grating of allogeneic skin (3), a IIB burn wound cleaned from dead tissue (4), the application of an allogeneic skin transplant (5) and the application of an external wound dressing (6).
Patients of our Center with IIB wounds and some patients with IIB/III wounds had the allogeneic skin transplant lead to a definitive closing of the wound, despite a previous nephrectomy, resulted in the stimulation of the growth of cells in the wound bed and the revascularization of the wound, as well the initiating of the epithelization process (Figure 6). This eliminated the need for an own skin transplant to be performed on the patient [49, 51]. Similar results have been observed by Oliver and associates, who have proven that allogeneic skin modulates the proliferation process, as well as differentiation of granulation tissue [53].
The patient on the day of admission to the Center (1), on the third day after the allogeneic skin transplant (2), on the 16th day from the hospital admission (the day of leaving the Center) (3).
Other patients with deep skin burn wounds had allogeneic skin used as a dressing preventing the loss of water, microelements and proteins, as well protecting them from bacteria and viruses. The dressing was a source of cytokines and growth factors stimulating chemotaxation and the proliferation of cells, stimulated the grantulation of tissue and prepared the stroma for a surgical intervention and provided grounds for the definitive closing of the wound thanks to an autologous skin transplant. Moreover, allogeneic skin is used in the Center when it is impossible to assess the depth of the wound and when there is a clear risk that it can deepen and the transplant can be rejected, as well as when the patient has a limited amount of source beds for own skin transplants [50]. Allogeneic skin is also applied on wounds coming from as escharotomy. To conclude, allogeneic skin is a good alternative to autologous skin transplants. An allogeneic skin transplant results in the complete healing of the wound, eliminating the necessity for own skin sourcing for the transplant, which could result in further complications, pain and scarring. It is worth noting, however, than allogeneic skin can only be a temporary wound dressing, allowing for and facilitating the autologous skin transplant, which remains one of the best methods of closing a burn wound [54].
In order to improve the properties and the longevity of the transplants, tissue engineering methods such as cell removal are used. The reason for the removal of cells from tissues/organs is the obtaining of a non-immunogeneic transplant, which could be populated
The use of skin substitutes is an alternative to auto-and allogeneic transplants in the treatment of wounds of various provenance, including burn wounds and chronic wounds. Skin substitutes have to meet certain criteria to fulfill their function as actual “substitutes”. They should not be immunogenic for the patient. They should modulate the proteolytic activity of the wound. The main role of synthetic skin substitutes is the provision of a bioresorptive scaffolding which facilitates cellular migration and deposition of the extracellular matrix [23]. This scaffolding should also stimulate angiogenesis and promote the migration of skin cells (fibroblasts), stimulate the synthesis of granulation and absorb and neutralize free radicals. The ideal skin substitutes should be commonly available and able to recreate various functions and layers of the skin in a short time. Skin substitutes have to undergo vascularization quickly and integrate fast into the wound bed of the patient. The majority of the currently available materials are based on scaffoldings of cattle collagen (e.g. Integra) or beef collagen as well as allogeneic keratinocytes and fibroblasts (Apligraf) [24]. Other substitutes are human-based skin equivalents, such as Apligraf®, Dermagraft® or TheraSkin® [25]. Other substitutes are acellular, natural biopolymer scaffoldings, such as Kolagen, Oasis®, GraftJacket®, DermACELL®, EpiFix®, Integra™, Promogran™, alginians and chitozans.
In the case of burn wounds, the first stage of treatment is the removal of dead tissue and a temporary wound closing, which at best may be definitive [30, 67]. A necrotomy procedure, removing the source of the infection, which is dead cells, affects the humoral reaction of the system and the amount of endotoxins in the patient’s blood [30, 68]. There are many substitutes that can be used for wound dressing. In our Center, we use human biostatic transplants skin, allogeneic amnion, cellular transplants (of keratinocytes and fibroblasts) as well as commercially available synthetic substitutes. Based on years of clinical research, we developed recommendations for the use of particular skin substitutes. We have experience in the use of three commercially available skin substitutes: Suprathel, Oasis and Biobrane. Shallow wounds, usually of the IIA type, benefit from Suprathel as an epidermis substitute. The decision on using a certain skin substitute is made every time by the lead doctor for every given patient. The final decision on the use of a synthetic substitute instead of an own skin transplant of an allogeneic transplant is often made in the operations room after the cleansing of the wound.
Suprathel is a resorbed epidermis substitute characterized by a high permeability of oxygen and steam and matching the physiological qualities of human skin. The pH of the dressing is initially 5.5 and a later 4.0 (in
We use Suprathel in our Center since 2011. That year, we used this substitute on burn wounds of 5 × 5 cm area in five patients and on the 9 × 10 cm in five patients. Starting in 2012 and upon the observation of the first clinically positive effects of the dressing, Suprathel became more and more popular in our Center. Below is a diagram detailing the use of Suprathel in 18 × 23 cm increments in 2012–2016 (Figure 7).
The amount of Suprathel used in 2012–2016.
During these years, Suprathel was mainly used in the Surgical Ward in artificial skin transplants. However, it was used twice in the Anesthesiology and Intensive Therapy Ward (Figure 8).
The wound (1) before the application of Suprathel (2) after the application of a substitute (3) upon heeling with Suprathel.
Deeper, IIB wounds are treated by Biobrane and Oasis in our Center. Biobrane is a dressing made of ultrathin, half-permeable membrane kept together by an elastic nylon band. It is made of a nontoxin mix of highly purified peptides made from collagen isolated from porcine skin and kept together by a nylon/silicone membrane. This structure ensures high elasticity and a fitting of the dressing to the wound. This substitute is highly adjoined and very hydrophilic and biocompatible. It is a 3D structure, containing a natural extracellular matrix facilitating the migration of cells, the filling of the wound and the stimulation of healing [45, 69]. In our Center, Biobrane was used as the first commercially available skin substitute. In 2008–2012, it was used in the burn wound ward: once in the 13 × 13 cm size and nine times in the 13 × 38 cm size. In the first stage, Biobrane was used in the cosmetic treatment of burn and chronic wounds and used with anesthetics. Later on, Biobrane was also used during surgery. Biobrane is a mutlipurpose biosynthetic dressing [70]. It is a relatively inexpensive, easy to store and reliable dressing when used according to recommendations [71]. Despite its several pros, Lal et al. suggest that it should only be used on wound not deeper than 25% TBSA to exclude the risk of infection [72]. Hubik et al. confirm that Biobrane carries a 37.8% risk infection [73]. Our experience confirms this data: in rare cases, an infection of the substitute occurred after it was transplanted on the cleansed burn wounds. Oasis is another skin substitute good for deeper wounds and chronic, seeding wound of the IIB type. This substitute is a natural matrix (Healthpoint) made of submucosal porcine lower intestine containing ECM (>90% collagen). It is thin (ca. 0.15 mm), half transparent and contains mainly type I collagen. The porcine component has a porous structure with pores of 20–30 μm that allow for the diffusion of oxygen and facilitates the survival of cells [74]. It maintains the biological activity of other skin elements that allow for binding of the cell growth factor and enzymes degrading the matrix, which allows an increased permeability of the cells and their accessing the fractured tissue. The matrix is the place of settling of glycosaminoglycans, proteoglycans, fibronectin and other growth factors, which gives is responsible for the substantial biological activity of this substitute [75, 76, 77]. This way, it gives not only the structural matrix, but provides growth factors as well, stimulating the angiogenesis and cellular migration, regulating the proteolytic activity and halting the extracellular matrix metalloproteinase: MMP-1, MMP-2 and MMP-9, affecting the migration of keratinocytes [78]. In our Center, we demarcated the matrix and applied the Oasis dressing during one procedure in the case of six patients between 2009 and 2015. In the case of each of these substitutes, the proper preparation of the wound bed is key. The wound has to be chemically or surgically cleansed. A very good method is VersaJet—a water knife removing dead cells. A wound cleansed of dead tissue has to be dressed with the substitute as recommended by the producer in terms of direction. The protection of the substitute is achieved by covering it with gauze soaked in vaseline (e.g. Jelonet), which is further covered by gauze dressings ready to injected with water and covered with bandage. The change of the dressing should happen no earlier than in the second day after the surgical procedure. Due to Suprathel being biodegradable, there is no need to remove it after the changing of the dressing unless and infection occurs. In this case, the infected substitute has to be removed immediately, cleanse the wound again and introduce antibacterial or antifungal procedures. To conclude, the use of commercially available skin substitutes in the treatment of burn and chronic wounds is a common practice in most Centers dealing with these kinds of wounds. Due to the high differentiation of the available products, each Center should develop its own procedure governing their good use. The procedures we described are ready recommendations for the use of commercially available skin substitutes which can be implemented in the treatment of patients with burn and chronic wounds. Due to their structure, epidermis substitutes are good for shallow wounds no deeper than IIA. Synthetic epidermis substitutes and natural skin substitutes may be equivalent to free skin transplants of medium depth and can be used on cleansed wounds no deeper than IIB [79, 80].
Another group of skin substitutes is made of acellular synthetic polymer matrix. While they are available on the market of skin substitutes, they have various limitations, such as limiting vascularization, heightening scarring, low mechanical resistance and the danger of being rejected by the patients’ immunological system. Synthetic skin substitutes often do not vascularize, which leads to the necrosis of cells and the final separation of the transplant from the wound [26]. An important limitation for the use of commercially available skin substitutes is the creation of scars, which lead to functional, mechanical and esthetic problems [27]. Even though scarring is a part of normal wound healing, it often leads to a pathological process. When the connective tissue fills the fractured skin part, it does not lead to the creation of a regular skin tone as the fibrous tissue lacks natural skin pigment. The connective tissue lacks hair follicles as well, which is why scars in hairy places can pose serious esthetic challenges. The uncovering and mechanisms of scarring would allow to determine the exact prophylaxis and therapeutic measures to undertake. A series of methods for the treatment of scars exist, yet neither one of them is fully effective. Since the use of one single method provokes a rapid relapse of the illness, a combined therapeutic approach is usually administered, allowing for a good cosmetic effect [28]. The combined therapeutic approach employing cryotherapy alone or combined with the use of steroids is one of the leading ways of scar treatment. Another method of improvement of the visual features of wounds is laser therapy. Its effectiveness is judged in various ways because of the type of wounds that can undertake this therapy. Its effects are usually augmented by corticosteroids. Another method, pressotherapy is based on treating scars by administering controlled pressure. Different compression models, compression clothes and clips’ are used to this effect [29]. When scar treatment methods prove insufficient, surgical intervention becomes necessary. It involves the removal of the pathological skin tissue fragment and replacing it with new and healthy skin, usually sourced from other parts of the patients’ body. Another surgical method for burn removal is the application of tissue stretchers (expanders). The use methods of burn treatment should result in the improvement of esthetic qualities of the patient, which further affect their self-confidence and quality of life [81]. More importantly, however, the aim of the therapy is to minimize clinical symptoms by minimizing or eliminating pain and burning and obtaining the full functionality of the joints affected by scarring. Wound treatment is a process of many stages, including various therapeutic methods depending on the level of maturity of the wound. The surgical procedure itself must be planned in a way that has in mind the caring for the scars. The removal of the necrosis should lead to retention of a reticular layer of the dermis, which allows for the faster healing of a wound thanks to less closely adhering scar. The use of VersaJet in the early resection of the necrosis positively impacts the look of the cleansed wounds. Depending on the type of transplant, the look of the wound at various stages of healing can be very different. The best esthetic effects are obtained by closing the wound with an autologous transplant of medium depth. A good cosmetic effect is also obtained by an
The wound before (1) laser therapy, after the first session (2) after the second session (3).
To conclude, the process of healing scars comes in stages and begins with the resection of the necrosis, which has to be carried out in such a way as to leave a layer of reticularis dermis and to perform the cuts Langer lines. This is the first stage of prophylaxis to prevent the formation of ugly scars. The type of transplant has a decisive influence on the appearance of scars, with the most cosmetically sound scars created by an medium depth solid transplant or an autologous keratinocytes and fibroblasts transplant in the scaffolding of a reticulated transplant. The very process of scar treatment should begin as soon as possible. Already the wound healing process can be aided by biostimulating lasers. The prophylaxis of scars includes the prevention of wound infection and contracted scars. Upon healing of the wound, the first step of scar treatment is a finger massage and the use of silicone gels and ointments, then pressure therapy using pressure clothing. Upon the forming a pathological scars, surgical methods such as the “Z” cut method and neighboring skin method, as well as laser therapy using the ablative CO2 laser.
Today’s global population is estimated to be over 7.9 billion people, which is expected to reach 9.9 billion in 2050, 34% higher than it is now [1]. Developing countries will account for nearly all of this overpopulation. To feed this growing population, agricultural lands must be used considerably more effectively, and production should be boosted by 70% compared to today’s values [2]. Besides, agricultural production areas are unfortunately facing major ecological challenges, owing to human misapplications, natural calamities, as well as the impact of global climate change [3]. As a result of these factors, today the condition of our current lands is deteriorating leaving us with no choice but to grow nutrient-rich, chemical-free agricultural produce for human and animal use while using far less water and arable land than in the past. This is why a focus on both quality and quantity should be placed on food production without depleting natural resources. Developing and disseminating improved agricultural methods and technologies are equally critical.
Since cultivation areas are dwindling year after year, fertilizer mineral is a world market item that is vital to produce a higher plant yield per unit area and attain food security. It must be available in adequate quantities and in the proper balance to close the gap between nutrient supply from soil and organic sources and nutrient demand for optimal crop development [4]. Not just that, fertilizer is critical for the nation’s economy to grow, as agriculture is the primary source of employment. By 2025, it will ensure food security for more than 8 billion people around the globe [5]. The increase in the use of chemical fertilizers by approximately 5 million tons in 10 years is a situation that should be considered while the agricultural areas are decreasing. However, it is more necessary to keep the soil’s plant nutritional balance by considering climate, soil, and plant characteristics rather than the amount of chemical fertilizers utilized, and fertilizing based on soil analysis is critical.
Fertilizer is recognized as one of the most valuable agricultural production inputs, and synthetic fertilizers are becoming increasingly popular around the world. The global fertilizer market was valued at $155.8 billion in 2019, with a compound annual growth rate (CAGR) of 3.8% predicted for the forecast period (2019–2024) [6]. Fertilizer consumption climbed from 10,777,779 million tons in 2015 to 14,495,815 million tons in 2020, a record high. The total global demand for fertilizers (N + P + K) was estimated at 198.2 million metric tons (mmt) in 2020/2021, according to the International Fertilizer Association (IFA). This was nearly 10 mmt, or 5.2% higher than in 2019–2020 and was the highest rise since the 2010–2011 fiscal year. Nitrogen experienced a 4.1% increase in demand to 110 mmt. Phosphorus demand increased by 7.0% (3.3 Mt), reaching 49.6 Mt., while demand for potash rose by 6.2% (2.2 Mt) to 38.5 Mt. [7]. In the last 50 years, the amount of chemical fertilizer used throughout the world has increased dramatically (Figure 1) [8].
Global usage of chemical fertilizer since 1970 [
Chemical fertilizers have also become more popular in Turkey in recent years, where the cultivation areas are decreasing every year, the need for fertilization is increasing, since more plant production per unit area is required. According to TUIK (Turkish Statistical Institute) 2021 statistics, both the use of fertilizers and nitrogen fertilizers has increased in agricultural production in Turkey in the last 10 years. TUIK statistics showed that annual fertilizer use in Turkey increased from 9,074,308 tons to 14,495,815 tons between 2010 and 2020, and the use of nitrogenous fertilizers increased from 5,995,500 tons to 9,774,691 tons within these values. The amount of fertilizer per unit production area is 107 kg/ha. The use of chemical fertilizers in agricultural inputs accounts for a share of 15–20% [9].
Advances in fertilization and agricultural applications have led to a significant increase in crop productivity in many regions, including Turkey. The most important chemical fertilizers applied to obtain more efficiency in plant production are those containing nitrogen, phosphorus, and potassium. Nitrogen fertilizers (N), however, are the most widely used chemical fertilizers in the world, as well as in Turkey, and play a unique role in plant production. Potassium fertilizers (K2O) are the second most consumed after nitrogen, followed by phosphorus fertilizers (P2O5) [8].
It has been determined that 87% of agricultural lands in Turkey have poor organic matter content [10]. Therefore, agricultural production is supported by fertilization, and nitrogen fertilizers constitute an important part of the total fertilizer applied. According to TUIK data, nitrogenous fertilizer usage rates as a percentage of total fertilizer use have shifted between 65 and 69% in the last 10 years [9]. Fertilizer use benefits plants in a variety of ways, including being a less expensive source of nutrients, having significant nutrient content and solubility, making it easily available to plants, and requiring less fertilizer, hence making it more suited than organic fertilizer [11]. Despite these advantages, mineral fertilizer has a number of negative environmental consequences as a result of rising consumption and decreased nutrient utilization efficiency. As a result, in intensive agricultural production systems, integrating intense cultivation with high nutrient utilization efficiency is a key difficulty.
Though conscious fertilization is desirable, the use of improper fertilizers can be extremely harmful, posing severe problems for current and future generations [12]. Sometimes, unfortunately, a wrong perception occurs among the producers of chemical fertilization. It is thought that more efficiency can be obtained by using more chemical fertilizers. Contrary to popular belief, the “LAW OF DECREASING PRODUCTION” is valid in fertilization. That is, the benefit derived from fertilization rises up to a point, after which continuing to apply fertilizer causes harm rather than a benefit.
The unintended and excessive use of chemical fertilizers to boost yields, as well as rising reliance on them, has a negative impact on the agricultural production system’s sustainability as well as financial losses in many countries today [13]. Certain factors, such as changes in fertilizer type, variations in application times, the producer’s lack of understanding in this area, and improper fertilizer applications, in particular, have been found to have quite substantial environmental consequences and threatening effects on the health and life of living creatures [14]. The inefficient and not demand-oriented fertilization applications in agricultural production can lead to soil acidity and soil crust, low organic matter and humus content, heavy metal accumulation, decrease in pH values, soil salinity, plant nutritional imbalances, limited plant growth, erosion, a decline in microbial activity and efficacy and emission of gasses containing substances that damage the atmosphere and the ozone layer, and eventually the greenhouse effect [15].
The issues at the forefront of the detrimental environmental effects of chemical fertilizers are highlighted here.
Excessive soil acidity induced by fertilizers is a major cause of soil degradation across the world. Fertilizers, especially nitrogen, acidify soil when applied in excess. This scenario has negative consequences, such as the crops’ incapacity to absorb phosphate, the proliferation of hazardous ion concentrations in the soil, hindrance of crop development, and suppression of microorganism activity [16]. If ammonium sulfate fertilizer is given to acidic soil, for example, the acidity level will become even higher. One-way ammonium sulfate fertilization of tea, according to research conducted in the Rize province of Turkey, considerably increased the acidity of low-pH soils. Currently, 85% of the land has fallen below pH 4, which is deemed critical. Likewise, in Nevsehir province, the pH of the soil has dropped to 2 as a result of nitrogen fertilization of potatoes grown in 100-fold increasing acidity over the last 25 years [17].
Hao et al. [18], carried out a field experiment to measure soil acidification rates in response to varied fertilizer sources and N rates, including control, optimal urea, conventional urea, optimized NH4Cl, and conventional NH4Cl plots, nitrogen addition resulted in average H+ production of 4.0, 8.7, 11.4, 29.7, and 52.6 keq ha−1 yr.−1, respectively. This was followed by a 1–10% decrease in soil base saturation and a 0.1–0.7 unit decrease in soil pH in the topsoil (0–20 cm). In a greenhouse study conducted to evaluate the effect of conventional nitrogen fertilizer on soil salinity and acidity, a significant rise in both soil acidity and salinity was witnessed as N input increased after one season, with pH decrease ranging from 0.45 to 1.06 units [19]. Moreover, after 21 years of application, chemical N fertilizer dropped the soil pH from 6.20 to 5.77, a 0.02 pH unit drop per year [20]. In another study, an evaluation of the impact of long-term fertilizing techniques on soil samples revealed a fall in soil pH from 8.4 to 7.5 [21]. Because nutrients are less available to plants in acidic soil, serious plant nutritional deficiencies are prevalent, resulting in overall crop reduction.
Heavy metal deposition in soils is mostly caused by the manufacture and consumption of industrial products, although fertilizers and pesticides used in agriculture also contribute significantly. Arsenic (As), copper (Cu), nickel (Ni), cadmium (Cd), and uranium (Ur), among other heavy metals, can build up in the soil following repeated chemical fertilizer applications, particularly phosphorus (P) fertilizers and their source material [22, 23, 24]. These toxic heavy metals not only pollute the environment, but they may also cause soil degradation, plant development retardation, and perhaps impair human health through food chain contamination harming the central nervous system, circulatory system, excretory system, and cardiovascular system, as well as cause bone damage, endocrine disruption, and possibly cancer [25].
Phosphorus (P) fertilizer is widely utilized in agriculture due to its vital function in crop growth and production [26]. However, P fertilizer has been recognized as the predominant cause of HMs pollution in soil when compared to potassium (K) and nitrogen (N) fertilizers [27]. According to a 10-year field trial, P fertilization aided Zn, Pb, Cd, and As buildup in the topsoil. With increasing P application, the threshold cancer risk (TCR) associated with As and Cd increased [28]. Likewise, another experiment concluded that frequent application of P fertilizer and the extended residence period of HMs may generate a large accumulation of HMs in soils [29].
Heavy metals are concentrated in agricultural soil as a result of improper application of commercial fertilizers, manure, sewage, or sewage sludge [30]. The results of the study conducted by Huang and Jin [31] suggested that the long-term usage of exaggerated synthetic fertilizers and organic manures contributed to the heavy metals (HMs) accumulation in the soils. Research carried out by Atafar et al. [32], confirmed that the fertilizer use enhanced the amounts of Cd, Pb, and As in cultivated soils. Before fertilization, the Cd, As, and Pb concentrations in the studied location were 1.15–1.55, 1.58–11.55, and 1.6–6.05 mg/kg, respectively; after harvesting, values were 1.4–1.73, 26.4 5.89, and 2.75–12.85 mg/kg soil for Cd, As, and Pb, respectively. The findings of another study concluded that chemical fertilizer usage increased the availability of Cu, Ni, Pb, and Zn as well as the buildup of Cd, Cu, and Zn in the greenhouse soil [33].
Salts are a common component of chemical fertilizers and are considered destructive to agriculture because they harm soil and plants. Increases in the salinity of the soil can be seen by natural or artificial means. Artificially induced salinity is the result of the accumulation of fertilizers used in large quantities over long periods of time in areas where intensive farming is practiced, making the soils unsuitable for production [22, 34, 35]. Following one season of conventional nitrogen fertilizer, electrolytic conductivity increased from 0.24 to 0.68 mS cm−1 [19]. Long-term intensive farming raised soil electrical conductivity (ECe), which rose from “low salinity” (1.5 dS m−1 0.49) to “highly saline” (6.6 dS dS m−1 1.35) levels [21].
Soil salinity is a major global issue that has a negative impact on agricultural output. Salinization of agricultural land diminishes economic advantages greatly, as demonstrated by Welle and Mauter [36] in California, where salinization lowered overall agricultural income by 7.9%.
Inorganic fertilizers used recklessly can cause nutritional imbalances in the soil, thus limiting the intake of other essential nutrients. If the common NPK type is frequently used, secondary and micronutrient deficiencies occur in the soil and crop. Excess nitrogen and phosphate fertilizers, for instance, enable the plant to absorb more potassium than it requires. In acidic soils, lime and lime-containing fertilizers lead to the retention of micro plant nutrients, such as P, B, Fe, and Zn in the soil. Over-applied phosphorus fertilizers also prevent the uptake of nutrients, such as Ca, Zn, and Fe, and reduce their efficacy [22, 37].
Soil compaction is a key component of the land degradation syndrome and a serious issue for modern agriculture, negatively impacting soil resources [38]. Overuse of fertilizers for extended periods of time and intensive cropping are two of the main causes of compaction. Chemical fertilizers damage soil particles, resulting in compacted soil with poor drainage and air circulation [39]. Reduced soil aeration has an impact on soil biodiversity. Microbial biomass may be diminished as a result of severe soil compaction. Soil compaction may not affect the amount of macrofauna, such as earthworms, but it does affect the distribution of macrofauna, which is important for soil structure.
Soil compaction leads to high soil strength and bulk density, poor drainage, poor aeration, limited root growth, erosion, runoff, and soil deterioration, hence resulting in low permeability, hydraulic conductivity, and groundwater recharge [40, 41]. High soil compaction stifles root growth, reducing the plant’s ability to absorb nutrients and water. Compaction, according to reports, reduces root growth and yield by more than 80% [42]. As the soil bulk density increases, nitrification drops by 50%, and plants use less N, P, and Zn from the soil [43]. The findings of the research conducted by Massah and Azadegan [44] suggested that in non-compacted and severely compacted soils, bulk density increased from 1.34 to 1.80 Mg.m−3, and penetration resistance increased from 0.89 to 3.54 MPa, respectively. Soil compaction reduced permeability by 81.4%, accessible water by 34%, and yields by 40%.
In agricultural production, the unintentional, excessive, or random application of chemical fertilizers and pesticides degrades the chemical, biological, and physical structure of the soil, resulting in a rise in pathogen and pest populations [45, 46]. Moreover, with intensive and unconscious chemical fertilizer applications, the amount of organic matter in the soil decreases, which adversely affects the microorganism activities and causes the structure of the soil to deteriorate. If the same fertilization errors are repeated, soil structures will deteriorate with each passing year, plant growth will slow as fertilizer doses are increased, and the overall amount of product obtained will decrease. Some of the fertilizers will not be able to hold on to the soil and will be removed with the water. The conversion of nutrients into forms that plants can benefit from will be reduced.
Soil microbial activity is a crucial component of soil health, and soil organisms serve as a mechanism for nutrient recovery, as well as provide a variety of other environmental functions. Chemical fertilizer misuse can have a detrimental and lethal effect on soil quality and microbial community structure, including earthworms, and other soil inhabitants. Prolonged consumption of chemical fertilizers can cause a significant drop in soil pH, which has been associated with a decrease in bacterial diversity and major changes in bacterial community composition [47]. Nitrogen usage in agriculture has a deleterious influence on the nitrogen cycle and the activities of related bacterial communities, including nitrogen-fixing microorganisms such as Rhizobium sp. [48]. Besides, excess nitrogen fertilizers limit the activities of nitrifying bacteria [49].
It is critical to emphasize the importance of understanding how to apply chemical fertilizers properly. Chemical fertilizers, as part of their larger threat to the environment, animals, and human health, eventually leak into our water bodies, such as ponds, streams, and groundwater, contaminating water supplies, exposing humans and animals to a variety of short- and long-term hazardous chemical effects on their health and bodies. In ideal conditions, it is estimated that roughly 2–10% of fertilizers interfere with surface and groundwater [50]. The accumulation of nitrates in the water emerges as a result of the use of N fertilizers in the agricultural field, which is increasing day by day. Even under ideal conditions, only 50% of the nitrogen fertilizer given to the soil can be taken up by plants; 2–20% evaporates, 15–25% combines with organic compounds in the clay soil, and 2–10% is discharged into streams, rivers, and streams with surface runoff [50, 51]. Nitrate, a frequent contaminant of surface and groundwater, can cause serious health concerns, including inflammation of the colon, stomach, and urine systems. Furthermore, these compounds have been reported as carcinogens that can have a harmful impact on human health. They also have the potential to induce disorders in infants, such as methemoglobinemia, a condition in which the blood carrying capacity is limited due to a decrease in hemoglobin.
Though the rise in agricultural productivity alleviated poverty, it also posed a threat to the ecosystem due to its negative consequences. Rising levels of synthetic fertilizer application for agricultural production, for instance, increase greenhouse gas emissions, eroding the protective ozone layer, and exposing humans to harmful ultraviolet radiation [52]. Above all, agriculture is responsible for a major fraction of the greenhouse gas (GHG) emissions that are driving climate change, accounting for 17% directly from agriculture activities and another 7–14% through land-use changes.
During the production of nitrogenous fertilizer, greenhouse gases, such as CO2, CH4, and N2O are released. Moreover, nitrous oxide emissions from soils, fertilizers, manure, and urine from grazing animals, as well as methane generation by ruminant animals and paddy rice agriculture, are the most significant direct agricultural GHG emissions. Both of these gases have a far larger potential for global warming than carbon dioxide.
Agriculture is the primary source of anthropogenic N2O emissions, accounting for 60% of total emissions. It has a 310-fold greater global warming potential than carbon dioxide. Excess nitrogen fertilizer application results in nitrogen oxide emissions (NO, N2O, NO2), which cause serious air pollution [51]. The primary issue with nitrous oxide emissions is the impact of global warming and the function of nitrous oxides in ozone degradation, encouraging the decomposition of the ozone layer [53] and resulting in atmospheric “holes,” exposing humans and animals to excessive UV radiation [54]. Water vapor, hydrogen sulfide, and chloro-fluoro hydrocarbons are among the other gases that contribute to ozone depletion [55].
After being volatilized or released from fertilized fields, ammonia is deposited in the atmosphere and oxidized to generate nitric and sulfuric acids, resulting in acid rain. Acid rain has the potential to harm flora, buildings, and species that live in lakes and reservoirs [56]. Methane emissions from transplanted paddy fields are also a major concern, as methane is a powerful greenhouse gas whose concentration is doubled when ammonium-based fertilizers are used. These gases all contribute to global warming and climate change [57].
Climate change is gaining traction, resulting in major global temperature spikes, as well as the prevalence of additional abiotic stressors that are reducing crop output. Significant production losses in major grain crops have been attributed to climate change, resulting in 3.8% yield reductions for maize and 5.5% for the wheat [58, 59].
Fertilization, which is one of the most essential inputs in agricultural operations, increases productivity on the one hand, but its overuse might have negative consequences on the other. Excessive usage of agricultural chemicals jeopardizes the long-term viability of agriculture. Today, the fast expansion in agricultural productivity has begun to slow down [45, 56]. Clean food production becomes inevitable with a healthy and reliable agriculture system that does not require chemicals.
Given that chemical fertilization cannot be completely eliminated in agricultural applications, in this scenario, sustainability initiatives and the usage of ecologically sound technologies can help achieve the goal of enhancing healthier crop productivity whilst eliminating unnecessary input and thereby mitigating harsh weather conditions, as well as improving soil health by sequestering carbon and retaining organic material and mineral nutrients in the soil [60]. Hence, it is vital to use alternatives, such as Plant-Growth-Promoting Rhizobacteria (PGPR), to support sustainable agricultural productivity and everlasting soil fertility and to build production strategies that will aid in the proliferation of beneficial soil microorganisms activities.
The rhizosphere is a well-defined ecological niche that consists of the volume of soil surrounding plant roots and is home to a wide range of microbial species [61, 62]. As a result of phytomicrobiome research, certain plant-microbe interactions that directly aid in plant nutrition are beginning to emerge [63]. Microbes have the power to positively influence plant growth and combat the majority of modern agriculture’s challenges, making them a promising alternative for agricultural sustainability. The rhizomicrobiome is indispensable for agriculture because of the extensive diversity of root exudates and plant cell debris that attract diverse and unique patterns of microbial colonization. Fertilizer requirements are often lower in soils with dynamic microbial ecologies and rich organic matter than in traditionally treated soils [64].
Despite the fact that the rhizosphere is home to a diverse range of microbes, including bacteria, fungi, algae, protozoa, and actinomycetes, bacterial colonies are predominant [65, 66]. The bacterial community in the soil, in particular, has the potential to proliferate quickly and use a wide variety of nutrient sources. A group of natural soil bacterial flora that resides in the rhizosphere and grows in, on, or around plant roots [67] and has a beneficial effect on the plant’s overall health is referred to as PGPR [68]. PGPR is a nonpathogenic, beneficial bacterium that promotes plant growth by modifying hormone levels and nutritional requirements, as well as reducing stress-related damage [69]. Nutrient absorption is thought to be increased as a result of the increased root surface area mediated by PGPR. Besides, they mineralize organic contaminants and are employed in polluted soil bioremediation [70]. When compared to other microorganisms, PGPR has unique characteristics, such as the ability to synthesize growth regulators, nitrogen fixation, phosphorus solubilization, siderophore generation, nutrients, and mineral solubilization, demonstrating their exceptional tendency in stimulating plant growth [71]. They are also environmentally friendly and ensure that nutrients from natural sources are available at all times. In addition to stimulating plant growth through their active mechanisms, the bacterial colonies in the rhizosphere have a considerable influence on suppressing phytopathogenic microorganisms. Beneficial rhizobacteria can emit antibiotics and other chemicals that are effective at inhibiting pathogens [72].
The fundamental impacts that rhizosphere bacteria have on plants have evolved into an important mechanism for protecting plant health in an environmentally sustainable manner [73]. They participate in a variety of biotic activities in the soil ecosystem to keep it active and productive for farming systems [74]. Furthermore, in recent times, PGPR has garnered much attention for its potential to substitute agrochemicals for plant growth and yield through multiple processes, including decomposition of organic matter, recycling of essential elements, soil structure formation, production of numerous plant growth regulators, degrading organic pollutants, stimulation of root growth, and solubilization of mineral nutrients, which are important for soil health [75]. It is cost-effective and environmentally beneficial to replace chemical fertilizers with PGPR, as well as to identify the most effective soil and crop management approaches in an attempt to develop more sustainable farming and soil conservation fertility [76]. The employment of phytomicrobiome representatives as a long-term disease prevention and nutrient supplement method in farming production might help to reduce the negative impacts of pesticide usage [77]. The inoculated plant’s biocontrol and induction of disease resistance, biological N2 fixation, phosphate solubilization, and/or phytohormone synthesis are all potential explanations for PGPR’s growth-promoting actions [78].
PGPR has both direct and indirect modes of action as a biofertilizer and a biopesticide.
One of the most prevalent ways for increasing agricultural production is to improve soil fertility. PGPR promotes soil fertilization through the biofixation and biosolubilization processes (Figure 2).
PGPR’s mechanism of action [
Nitrogen (N) is found in all forms of life and is one of the most significant mineral nutrients for plant growth as it is a crucial component for various physiological activities in plants, including photosynthesis, nucleic acids, and protein synthesis [80]. Unfortunately, due to the low degree of reactivity, no plant species are capable of directly converting atmospheric dinitrogen into ammonia and using it for growth, hence making the plants dependent on biological nitrogen fixation (BNF). Nitrogen fertilizer, as being the most effective approach to nitrogen supplementation, has been an integral part of modern crop production and agricultural systems; yet, their continued and undesirable use is contaminating the climate. Though carbon dioxide (CO2) is widely regarded as the primary cause of climate change, nitrous oxide (N2O), which has a 265-fold higher heat-trapping efficiency than CO2 [81], is indeed a significant contribution. PGPR in this regard is a potential alternative to minimize the fertilizer requirements to a certain degree as the majority of the plant microbial community can either directly fix atmospheric nitrogen through legume-rhizobium interaction or indirectly by helping nitrogen fixers via their secretion [82].
Worldwide, total N fixation is estimated to be ∼175Tg, with symbiotic nitrogen fixation in legumes accounting for ∼ 80 Tg by fixing 20–200 kg N year-1, while the remaining nearly half (∼88 Tg) is industrially fixed during the production of N fertilizers [83]. The most prominent symbiotic nitrogen fixer is Rhizobium [84], whereas Azospirillum, Acetobacterdiazotrophicus, Azotobacter, Herbaspirillum, Cyanobacteria, Bacillus, Paenibacillus, Gluconacetobacter, and Azoarcus, etc., represent the free-living N fixers [85].
Symbiotic nitrogen fixation: A mutualistic association between a microorganism and a plant is known as symbiotic nitrogen-fixing. The N-fixing symbiosis between rhizobia and legumes is the most well-studied and utilized beneficial plant-bacteria interaction. In this interaction, legumes supply rhizobia with reduced carbon and a protected, anaerobic environment that is necessary for nitrogenase activity, while rhizobia feed legumes with biologically accessible nitrogen. The bacteria enter the root first, causing the growth of nodulation, which converts atmospheric nitrogen into usable forms (primarily NH3) [86]. Rhizobia can fix up to 200 kg of nitrogen ha − 1 by establishing symbiotic relationships with more than 70% of leguminous plants, thus making it available to plants.
Free-living nitrogen-fixing: Several nitrogen-fixing microorganisms do not interact in a symbiotic manner. These microorganisms are free-living and rely on plant leftovers or their own photosynthesis to exist. Although free-living nitrogen fixers do not enter the plant’s tissues, a tight interaction is developed where these bacteria reside close enough to the root that the atmospheric nitrogen fixed by the bacteria is taken up by the plant, resulting in greater nitrogen absorption. Besides, other bacteria that do not fix nitrogen have been demonstrated to boost nitrogen uptake in plants, resulting in increased nitrogen use efficiency [87], most likely due to increased root development, which allows plants to reach more soil [63]. Evidence of PGPR involvement in the plant N budget has been identified for various plants, particularly sugarcane [88].
Rhizobial N-fixation is an integrated approach for disease control, growth stimulation, as well as providing and maintaining the nitrogen level in agricultural soils around the world, thus minimizing the need for extensive N-fertilizer application and limiting the soil and environmental challenges associated with it.
Phosphorus (P) is the most significant vital element in plant nutrition (N), alongside nitrogen [89]. It is involved in a number of major metabolic activities in plants, including macromolecular biosynthesis, photosynthesis, respiration, energy transfer, and signal transduction [90]. Although most soils hold a significant amount of phosphorus, which builds over time as a consequence of fertilizer treatments, plants have access to only a small portion of it. Despite the fact that P is abundant in both organic and inorganic forms in the soil, only 0.1% of it is available to plants because 95–99% of phosphate is either insoluble, immobilized, or precipitated [91]. Plants can absorb mono and dibasic phosphate on their own, but organic and insoluble phosphate must be mineralized or solubilized by microorganisms [92]. Phosphate anions are highly reactive and, depending on the soil quality, can be trapped by precipitation with cations including Mg2+, Ca2+, Al3+, and Fe3+. Plants cannot absorb phosphorus in these forms because it is highly insoluble. As a result, plants only get a small percentage of the total.
When deficient, phosphorus-based fertilizers are typically used to replenish soil P, which is readily available to plants. Supplementing P with commercial fertilizers, however, is not an ideal option due to their high cost and sometimes inaccessibility to plants since they are easily lost from the soil and subsequently mix with local streams, contaminating both terrestrial and aquatic environments [93]. Therefore, phosphorus solubilization, in addition to nitrogen fixation, is also vital biologically. Phosphate solubilization is among the most profound consequences of PGPR on plant nutrition. Persistent plant growth, PGPR, plays a major role in solubilizing phosphorus [94]. The potential of various bacterial species to solubilize insoluble inorganic phosphate compounds such as dicalcium phosphate, tricalcium phosphate, rock phosphate, and hydroxyapatite has been documented by many researchers. Phosphate can be dissolved in insoluble forms by a variety of PGPR, including Pseudomonas, Bacillus, and Rhizobium. PGPR solubilizes P by employing a number of mechanisms, including the synthesis of organic acids and extracellular enzymes, to make use of inaccessible forms of P, hence assisting in the availability of P for plant absorption. Miller et al. [95] pointed out two processes—acidification of the external medium via the release of low molecular weight organic acids (such as gluconic acid) that chelate phosphate-bound cations and the formation of phosphatases/phytases that hydrolyze organic forms of phosphate compounds. Phosphorus solubilizing bacteria (PSB) has been shown to lower the recommended P dose by approximately 25% [96] and is even more efficacious when combined with other PGPRs or mycorrhizal fungi, reducing the P supplementation to 50%. As a result, the risk of P runoff and eutrophication is mitigated [97].
Potassium (K) deficit has become a severe crop production bottleneck. Plants with insufficient potassium have poor root development, low seed production, a slow growth rate, and a decreased yield. Soluble potassium concentrations in soil are typically low; over 90% of the potassium in the soil is in the form of insoluble rocks and silicate minerals [98]. Several microbes, particularly fungal and bacterial genera, have close connections with plants and can release potassium in accessible form from potassium-bearing minerals in soils through the synthesis and secretion of organic acids [99, 100, 101]. Setiawati and Mutmainnah [101] synthesize organic acids produced by soil microorganisms, such as acetate, ferulic acid, oxalate, coumaric acid, and citrate, which significantly increase mineral dissolution rates and proton production by acidifying the soil rhizosphere and resulting in mineral K solubilization. As a result, using potassium-solubilizing PGPR as a biofertilizer in agricultural production can reduce agrochemical use while also encouraging environmentally friendly crop production.
Iron (Fe) is a major bulk mineral abundantly available on Earth, yet it is inaccessible in the soil for plants, owing to the fact that Fe3+ (ferric ion), the most common form of Fe found in nature, is hardly soluble [102]. PGPRs are the right fit to address this issue as they produce siderophores, which are tiny organic compounds that increase Fe absorption capability when it is scarce. Since PGPR can form siderophores, they are a valuable asset in supplying the plant with the necessary iron. Siderophores released by PGPRs boost plant growth and development via facilitating access to Fe in the soil surrounding the roots [103]. Plant growth can be stimulated directly by siderophore-producing bacteria, which improves plant Fe intake, or indirectly by suppressing the activities of plant pathogens in the rhizosphere, which limits their Fe availability [104]. Pathogen suppression is induced by the synthesis of siderophores, which decrease pathogen survival by chelating available Fe and therefore restricting pathogen survival [105]. In the presence of other metals, such as nickel and cadmium, a robust siderophore, such as the ferric-siderophore complex, is crucial for Fe uptake by plants [106]. Siderophores alleviate stress on the plants caused by potentially hazardous metals, such as Al, Cd, Cu, Pb, and Zn, found in polluted soil via forming stable compounds with them [107]. This phenomenon is beneficial for reducing plant stress induced by potentially harmful metals found in contaminated soils. Furthermore, siderophore-expressing rhizobacteria could be a potential alternative to chemical fertilizers by concurrently addressing salt-stress effects and Fe limitation in saline soils.
One of the many advantages of rhizobacteria in encouraging plant growth and controlling plant diseases is their ability to synthesize polysaccharides. Multifunctional polysaccharides, for instance, structural polysaccharides, intracellular polysaccharides, and extracellular polysaccharides, are synthesized by specific bacteria. Exopolysaccharide production is critical for biofilm development, and root colonization can influence microbial interactions with root appendages. The colonization of plant roots by EPS-producing bacteria aids in the separation of free and insoluble phosphorus in soils, circulating critical nutrients to the plant for appropriate growth and development, as well as protecting it against disease attacks. EPS-producing bacteria have a variety of roles in plant-microbe interactions, including protection against desiccation, stress [108], adherence to surfaces, plant invasion, and plant defense response [109]. Plant exopolysaccharides produced by plant-growth-enhancing rhizobacteria are critical in stimulating plant growth because they act as an active signal molecule during beneficial interactions and generate a defense response during the infection phase [110]. Some plant-growth-promoting rhizobacteria that produce exopolysaccharides can also bind cations, including Na+, implying that they may play a role in limiting the amount of Na + available for plant uptake and thereby reducing salt stress [111].
Phytohormones, commonly known as plant growth regulators, are organic chemicals that, at low levels (less than 1 mM), promote, inhibit, or modify plant growth and development [112]. Phytohormones are categorized based on where they act. Botanists recognize five main kinds of phytohormones: Auxins, Gibberellins, Ethylene, Cytokinins, Ethylene, and Abscisic acid.
Phytohormones stimulate root cell proliferation by overproducing lateral roots and root hairs, resulting in increased nutrition and water intake [113]. This is crucial for regulating nutrient uptake depending on soil composition and environmental circumstances. Slower primary root development and a spike in the proportion and length of lateral roots and root hairs are the most common effects.
Phytohormones play an important role in regulating developmental processes and signaling networks that are involved in plant adaptation to a variety of biotic and abiotic stressors [114]. Abiotic stressors, however, disrupt plant growth by altering endogenous levels of phytohormones [115]. Surprisingly, some bacteria, such as PGPR, may stimulate plants to produce phytohormones.
A diverse spectrum of rhizospheric microorganisms is capable of producing growth hormones that can promote cell proliferation in the root architecture by inducing an increase in nutrition and water intake by encouraging root hair growth, thus regulating overall plant growth and development, as well as activating pathogen defensive responses [116]. Important biological rhizobacteria can adjust to their surroundings and develop stress tolerance by repairing plant roots. The production of growth metabolites by PGPRs may help provide water stress resistance in host root colonization, resulting in higher optimal crop output.
Auxin is a critical molecule that regulates most plant functions, either directly or indirectly, and indole-3-acetic acid (IAA) is the most abundant and physiologically potent phytohormone that regulates gene expression by upregulating and downregulating it [116, 117]. More than 80% of rhizospheric bacteria have been known to be capable of synthesizing and releasing auxins. IAA produced by PGPR regulates a wide range of processes in plant development and growth, including cell division, differentiation, organogenesis, tropic responses, primary root elongation, and the formation of lateral roots [118]. As a result of the increased root surface area and length mediated by bacterial IAA, plants have better access to soil nutrients. Under salinity stress circumstances, the secretion of IAA by PGPR may have a key function in managing and regulating IAA concentrations in the root system, resulting in improved plant salinity stress responses [119]. Besides, microbe-induced IAA can boost root and shoot biomass output in water-stressed situations [120].
Gibberellins (GA) are another type of phytohormone produced by rhizobacteria. Different activities in higher plants, such as seed germination, root and leaf meristem size, cell division and stem elongation, floral induction, fruiting, and the flowering process, growth of the hypocotyl and stem, are all mediated by GA [121]. However, shoot elongation is by far the most significant physiological function of GA [122], which modifies the morphology of plants.
Cytokinins are a type of growth regulators that are responsible for seed germination, production of shoots, vascular cambium sensitivity, the proliferation of root hairs, improvement of cell division and root development, interactions of plants with pathogens, and nutrient mobilization and assimilation [123, 124], but suppress root elongation and lateral root formation [125, 126]. They are especially important for the cell cycle’s progression. Cytokinin, either alone or in combination with other phytohormones like abscisic acid and auxin, can help salt-stressed plants grow faster while also improving resistance by altering the expression of genes [127]. PGPRs, such as Bradyrhizobiumjaponicum, Azospirillumbrasilense, Pseudomonas fluorescens, Arthrobactergiacomelloi, Paenibacilluspolymyxa, and Bacillus licheniformis, have been demonstrated to produce cytokinin (particularly zeatin) [69]. Cytokinin-producing PGPRs act as biocontrol agents against a variety of pathogens [128].
PGPR has been proven in various investigations to be effective in both creating and regulating the amounts of ABA and gibberellic acid in plants. Gibberellins promote primary root elongation and lateral root development. Several PGPR, including Azotobacterspp, Azospirillumspp, Achromobacterxylosoxidans, Gluconobacterdiazotrophicus, Acinetobactercalcoaceticus, Bacillus spp., and Rhizobia spp., have been found to produce gibberellin [129].
The role of ABA under drought stress, for example, is well-known. Under conditions of water deficit, increased ABA levels cause stomata to shut, limiting water loss. This hormone, on the other hand, offers a variety of benefits during lateral root development [129]. Inoculation with Azospirillumbrasilense Sp245 increased ABA content in Arabidopsis, especially when grown under osmotic stress [130].
In addition to their roles in plant RSA, these two hormones are involved in plant defense mechanisms. As a result, PGPR, which produces these hormones, may affect the hormonal balance involved in plant defense, including the jasmonate and salicylic acid pathways [131].
As climate change conditions worsen, extreme environmental conditions that can cause significant annual losses in total crop output are now more prevalent worldwide [132, 133]. Many biotic and abiotic stresses are causing havoc on the sector, resulting in enormous plant productivity losses all around the world. Stress factors comprise nutrient shortages, heavy metal contamination, high wind, extreme temperatures, salinity, drought, illnesses, plant invasions, pests, salt, and soil erosion [69].
As a result of climate change, abiotic stresses, such as drought and high temperatures, have risen in frequency and intensity, resulting in 70% losses in major staple food crops, posing a danger to global food security [134]. Drought and high soil salinity, as well as their downstream impacts, such as osmotic, oxidative, and ionic stress, are regarded as important hindrances to long-term agriculture production [135]. Stressed plants suffer from internal metabolism disruption due to metabolic enzyme inhibition, substrate scarcity, excessive need for different chemicals, or a combo of the following. To endure unfavorable conditions, metabolic reconfiguration is required to comply with the demand for anti-stress compounds, such as suitable solutes, antioxidants, and proteins [136].
Agricultural breeding practices have tried to produce species that are more productive in unfavorable environments for ages. However, crop breeding for abiotic stress resistance has been impeded by a lack of reliable and consistent traits. Tolerance to stress is influenced by a number of genes working together. Furthermore, using agrochemicals to address biotic stresses and nutritional deficits contributes to environmental degradation, has a negative influence on the biogeochemical cycle system, and puts people at increased risk. The potential repercussions of the aforementioned stresses are significant, necessitating the development of robust, cost-effective, and environmentally acceptable methods to mitigate these stresses’ harmful effects on plants. As a result, there has been a spike in interest in environmentally friendly and organic agriculture techniques. Plant growth stimulants have been utilized in bio-fertilization, root revitalization, rhizoremediation, disease resistance, and other modes of microbial revival [137].
The efficient approach of PGPR can alleviate stresses that cause serious damage to crop yield, hence, the application of PGPR and/or their byproducts, which can help plants successfully resist extreme environmental circumstances, is one of the most eco-friendly ways [138]. Some PGPR genera, for instance, P. fluorescens, produce the enzymes 1-aminocyclopropane-1-carboxylate (ACC) deaminase and hydroxyacetophenone monooxygenase, which break down the ethylene precursor ACC to a-ketobutyrate and ammonia, thereby protecting plants from abiotic stressors [139]. The most destructive factors that reduce agricultural productivity are salinity and drought [140]. Furthermore, greater ethylene levels in the plant lead to premature fatuity symptoms, including leaf yellowing, abscission, and desiccation/necrosis [141]. PGPR is essential to minimize ethylene concentrations in plants, which in turn reduces stress.
During dry spells, turgor pressure and water potential have a significant impact on plant functionality. Drought stress results in substantial losses in agricultural output and the flow of nutrients, such as sulfates, nitrates, calcium, silica, and magnesium, as well as a reduction in photosynthesis activity [142]. To achieve sustainable agricultural productivity, bacterial colonies in the rhizosphere and endorhizosphere stimulate the plant to withstand drought [143]. PGPR releases osmolytes, which function in tandem with those obtained from plants to keep plants healthy and improve their growth and development, as well as withstand drought-related stress and excessive salt levels in the soil [144]. According to research findings, inoculating plants growing in dry and semi-arid areas with beneficial plant-growth-promoting rhizobacteria (PGPR), which enhances plant abiotic stress tolerance with an osmotic component, could improve drought tolerance and water utilization efficiency. PGPR-induced root development, nutrient uptake efficiency, and systemic tolerance have been proposed as biochemical changes in plants that result in increased abiotic stress tolerance (IST) [78].
Rise in global temperature and fluctuations in precipitation as a result of climate change have resulted in unprecedented crop pests and illnesses in various parts of the world [82]. Biotic agents, such as pathogenic bacteria, viruses, fungi, nematodes, protists, weeds, insects, and arachnids, are a prevalent concern in crop production and a long-term danger to sustainable agriculture and ecosystem stability around the world [145]. These species can induce biotic stress in their hosts by interfering with normal metabolism, injuring their plant hosts, reducing plant vigor, limiting plant development, and/or inducing plant mortality. Biotic stress has an impact on co-evolution, ecosystem nutrient cycling, population dynamics, horticulture plant health, and natural habitat ecology [146]. They also result in pre- and post-harvest damage to agricultural crops [147].
According to the FAO, pests are estimated to be responsible for up to 40% of global agricultural production losses each year. Plant diseases cost the world economy more than $220 billion per year while invading insects cost at least $70 billion [148].
Pesticides are chemical compounds that are used to prevent or control pests. However, these are poisonous compounds that pollute soil, watercourses, and plant life. The inappropriate application and overuse of such chemicals have triggered numerous problems (e.g., the emergence of resistance in target organisms, food contamination, and environmental pollution) [149]. Pesticide use causes morphological, physiological, biochemical, and molecular changes in plants that can have a detrimental effect on the plant’s development and growth, leaving chemical residues in numerous plant tissues, as well as insect resistance to pesticides [150, 151]. Besides, pesticides cause oxidative stress in plants, hinder physiological and biochemical pathways, cause toxicity, obstruct photosynthesis, and reduce crop yield. The overgeneration of reactive oxygen species has a negative effect on non-targeted plants. Reactive oxygen species are highly reactive in nature, causing oxidative damage to lipids, nucleic acids, proteins, carbohydrates, and DNA in plants, as well as disruptions in other biochemical and physiological cell processes [152].
The rising number and intensity of pesticide consumption have presented a significant obstacle to the pests being targeted, leading them to disseminate to dynamic habitats and/or adjust to the changing settings [153]. Resistance is currently the greatest serious impediment to the effective use of pesticides. Many pest species have developed resistance to pesticides as a result of their use around the World [154].
Pesticides’ impact on non-target species has been a source of debate and worry around the world for decades. Pesticides’ adverse impacts on non-target arthropods have been well documented [155]. Natural insect adversaries, such as parasitoids and predators, are tragically the most vulnerable to insecticides and suffer the most harm [156]. Natural enemies that ordinarily keep small pests in check are sometimes harmed, which can lead to subsequent pest outbreaks.
Not just that, pesticide use may have a negative impact on the earthworm population. Earthworms contribute to the improvement and maintenance of soil structure by producing channels in the soil that allow for aeration and drainage. In agricultural settings, they are regarded as a key indicator of soil quality [157]. Earthworms are harmed by a wide range of agricultural practices, with indiscriminate pesticide usage being one of the most serious [158]. Yasmin and D’Souza [159] found that pesticides have a dose-dependent effect on earthworm reproduction and proliferation.
Moreover, pesticide usage has the potential to destroy biodiversity. Degraded pesticides interface with the soil as well as its inhabitants, affecting microbial diversity, biochemical processes, and enzyme activity [160]. Any change in the activity of soil microorganisms as a result of pesticide application disrupts the ecological environment, resulting in a loss of soil quality. In crops cultivated on soils excessively exposed to chemical pesticides, nutrient loss and disease incidence are widespread [161], which is unfavorable from the perspective of agricultural soil management for food and nutritional security.
Exogenous pesticide residues may also alter the efficacy of beneficial root-colonizing microbes, such as fungi, bacteria, algae, and arbuscular mycorrhiza (AM), in soil by affecting their growth, and metabolic activity, among other things [162].
Furthermore, pesticides are widely distributed when they are transported across long distances by air or water [163]. Several pesticides have a prolonged half-life (up to years) in the environment; for example, the half-life of HCH in water is determined to be 191 days [164], hence posing a threat to aquatic creatures.
The mode of pesticides’ action is hazardous not just to the target organisms but also to non-target creatures, such as humans. The physicochemical parameters of the active ingredient are known to influence pesticide diffusion into plant tissue. As a result, pesticides with a systemic effect are absorbed by the roots or leaves and transported throughout the plant, as a result, they pose a major health risk to anyone who consumes them [165]. Pesticides’ negative impacts on human health have begun to emerge as a result of their toxicity, longevity in the environment, and tendency to penetrate the food chain. Based on the side effects, chemical pesticides employed in crop protection to limit the damage caused by pathogens and pests in agricultural areas pose significant long-term risks and challenges to life forms. Pesticides can penetrate the human body through immediate exposure to chemicals, contaminated water, or polluted air, as well as through food, particularly fruits and vegetables. Pesticide exposure can cause both acute and chronic disorders. Humans develop chronic sickness after being exposed to sub-lethal levels of pesticides for extended periods of time [166]. They are believed to stimulate cancer [167] and fetal malformations [168], and they are nonbiodegradable [169]. Encountering pesticides with genetic makeup, resulting in DNA damage and chromosomal abnormalities, is one of the primary pathways that lead to chronic disorders, such as cancer [170]. Pesticides can also cause oxidative stress by modifying the amounts of antioxidant enzymes, including glutathione reductase, superoxide dismutase, and catalase, which increase reactive oxygen species (ROS) [171]. Pesticide-induced oxidative stress has been linked to a number of health concerns, including Parkinson’s disease and glucose homeostasis disruption [170].
Given the pervasive harmful effects of pesticides on plants, soil, the environment, and human health, an environmentally friendly replacement is required, making PGPR a viable option.
Biocontrol agents are bacteria that suppress the occurrence or severity of plant diseases, whereas antagonists are bacteria that have antagonistic behavior toward a pathogen. PGPR can be used as a biocontrol agent (Figure 3) to protect plants from pathogens, such as viruses, bacteria, insects, and fungi [173].
PGPR as biocontrol agent [
When compared to chemical pesticides, PGPR has unique benefits, including being harmless to mankind and nature, dissolving more quickly in soil, and having a lesser possibility of pathogen resistance development [174]. Because plants, unlike animals, are unable to use avoidance and escape as stress-relieving strategies, their existence has been marked by the establishment of extraordinarily favorable partnerships with their more mobile partners, microbes. PGPR and its interactions with plants are economically harnessed [175], and they hold considerable promise for long-term agricultural sustainability. Plants that have been inoculated by immersing their roots or seeds in PGPR cultures overnight have been shown to be extremely resistant to many forms of biotic stress [176].
Antibiotic synthesis is one of the most robust and well-studied biocontrol mechanisms of PGPR against phytopathogens during the last two decades [177]. Antibiotics are low-molecular-weight toxins that have the ability to kill or inhibit the growth of other bacteria. The Bacillus genus and Rhizobacteria are the most significant for antibiotic synthesis [178]. Antibacterial and antifungal antibiotics are produced by Bacillus amyloliquefaciens and B. subtilis, including subtilin, bacilysin, and emicobacillin [179].
Induced systemic resistance (ISR) is a physiological condition of increased defensive capacity triggered by a specific environmental stimulation. Conrath et al. [180] define ISR as “an enhanced defensive ability of plants in response to specific pathogens stimulated by beneficial microorganisms present in the rhizosphere,” a scenario wherein the interaction of certain microorganisms with roots results in plant tolerance to pathogenic bacteria, fungi, and viruses. ISR can also be induced by certain environmental cues that cause upregulation of plants’ innate defenses in response to the biotic assault, allowing plants to respond faster and stronger to subsequent pathogen attacks [181]. Following the pathogenic invasion, signals are produced, and a defense mechanism is activated via the vascular system. Among the defense mechanisms produced by ISR in plants are cell wall reinforcement [182], production of secondary metabolites, and accumulation of defense-related enzymes, such as chitinases, glucanases, peroxidase, phenylalanine ammonia-lyase, and polyphenol oxidase, lipoxygenase, SOD, CAT, and APX along with some proteinase inhibitors [183].
ISR is not unique to a particular pathogen but can benefit a plant by evading a variety of diseases. Various plants develop systemic resistance to a wide range of plant diseases and a variety of environmental stresses when primed with PGPR [184]. ISR is among the pathways through which PGPR might minimize the onset of various plant diseases by modifying the physical and biochemical attributes of host plants and thereby boosting plant growth [185]. After applying plant-growth-promoting rhizobacteria, diseases of fungal, bacterial, and viral origin, as well as damage caused by insects and nematodes, can be decreased [186].
Non-pathogenic microorganisms promote ISR, which starts in the roots and extends to the shoots [187]. ISR stimulates plant defense mechanisms and shields unexposed regions of plants against future pathogenic attacks by microbes and insects. The signaling of ethylene and jasmonic acid in the plant is involved in induced systemic resistance, and these hormones increase the host plant’s defense responses against a range of plant diseases [188]. Lipopolysaccharides (LPS), siderophores, homoserine lactones, 2, 4-diacetylphloroglucinol, cyclic lipopeptides, and volatiles like acetoin and 2, 3-butanediol are only a few of the bacterial components that cause induced systemic resistance [189].
Plant-growth-promoting rhizobacteria use another mechanism to promote growth—enzymatic activity, producing compounds that inhibit phytopathogenic agents [190]. Rhizobacterial strains that promote plant growth can secrete enzymes, including ACC-deaminase, phosphatases, chitinases, 1,3-glucanase, proteases, dehydrogenases, and lipases, among others [94, 191]. They excrete cell wall hydrolases, which are used to break down cell walls, neutralize infections, assault pathogens, and cause hyperparasitic activity [192]. Plant-growth-promoting rhizobacteria suppress pathogenic fungi, such as
In recent years, microbial volatile organic compounds (mVOC) have been shown to play an important role in microorganism–plant interactions [196, 197, 198]. VOCs are produced by a wide range of soil microorganisms. Bacillus bacteria are the most common microbes that produce antimicrobial MVOCs. Bacterial volatiles have a key function in encouraging plant growth by regulating phytohormone synthesis and metabolism.
They can also promote plant health by acting as antibacterial, nematicidal, oomyceticidal, and antifungal agents, as well as eliciting plant immunity via the salicylic acid (SA) and jasmonic acid (JA) pathways [199]. These molecules have the potential to increase plant growth and development and induce systemic resistance (ISR) against pathogenic organisms, resulting in improved agricultural well-being [200]. Through the SA-signaling pathway, acetoin from the bacteria B. subtilis produces systemic resistance in
Depending on the species, the quantity and composition of VOCs varies [202]. 2, 3-Butanediol is a volatile organic compound (VOC) generated by a variety of microorganisms that, among other things, can activate plant resistance against pathogens. This mVOC generated by
The antagonistic activity of PGPR also results in the production of volatile compounds. HCN, a well-studied biocontrol agent, commonly known as prussic acid, is a broad-spectrum volatile secondary metabolite generated by numerous rhizobacteria and is crucial for the biological control of several infectious microorganisms in the soil. Most metalloenzymes are inhibited by their cyanide ion, particularly copper-containing cytochrome c oxidases [204]. HCN-producing Pseudomonas strains are employed in the biological control of tomato bacterial canker [205]. For instance, the inhibition of Macrophomina phaseolina and Meloidogyne javanica caused sunflower charcoal rot and tomato root-knot diseases and has been related to bacterial strains secreting HCN [206]. The inhibitory activity process starts in the mitochondria, where HCN inhibits electron transport, reducing energy supply to the cell and finally causing pathogenic organisms to die.
Plants generate a lot of “stress ethylene” (ET) after the onset of a disease or stress. Much of the growth inhibition that happens as a result of environmental stress is due to the plant’s response to elevated levels of stress ethylene, which aggravates the stressor’s response. Likewise, ethylene production inhibitors can considerably reduce the intensity of various environmental stressors. The production of defense enzymes, including 1-aminocyclopropane-1-carboxylate (ACC) deaminase, has also been linked to PGPM’s ability to protect against biotic stress [207]. Numerous results suggest that seed inoculation with bacterial endophytes increases plant defense. This is because bacteria produce the enzyme 1-aminocyclopropane-1-carboxylate (ACC), which can cleave ET into ketobutyrate and ammonia, lowering the presence of this enzyme linked to plant stress and physiological impairment [208]. As a result, if ACC deaminase-containing bacteria can reduce plant ethylene levels, treating plants with these organisms may give some defense against the stress inhibitory effects. The synthesis of ACC-deaminase by
To meet the ever-increasing nutritional demand of the rapidly increasing world population, chemical fertilizers must be employed. However, unintended and excessive use has a variety of negative repercussions on the natural environment resulting in soil degradation, global warming, and climate change, necessitating the search for environmentally sound alternatives. PGPR, in this regard, is a realistic choice for agricultural production that does not deplete natural resources. Plants and microbial communities in the soil have evolved a variety of biotic connections, ranging from commensalism to mutualism. Plant-PGPR collaboration is an important aspect of this web of interactions, promoting the growth and health of a variety of plants. PGPR has recently received a lot of attention for its potential to replace agrochemicals for plant growth and yield through a variety of processes, including decomposition of organic matter, recycling of essential elements, formation of soil structure, production of numerous plant growth regulators, fixation of atmospheric nitrogen, degradation of organic pollutants, stimulation of root growth, solubilization of phosphorus, production of siderophore, and solubilization of mineral nutrients, all of which are important for soil and plant health. Furthermore, they are cost-efficient and environmentally sustainable and assure that nutrients from natural sources are always accessible. Besides, bacterial colonies in the rhizosphere have a considerable impact on phytopathogenic microorganism reduction, in addition to boosting plant growth through active processes, hence the use of phytomicrobiome representatives in farming production as long-term disease prevention and nutrient supplement strategy could also help to mitigate the detrimental effects of pesticide use.
As a nutshell, in the face of global climate change, PGPR could be a more environmentally friendly option than chemical fertilizers.
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It was used to overcome liver, cardiovascular and gastrointestinal problems and for treatment of some types of infectious disease. Particularly, good results were achieved in the case of application of this product for therapy of infected, difficult to heal wounds. The high health-promoting properties of honey have been recently confirmed in many research investigations. The antimicrobial activity of this product is highly complex. Generation of hydrogen peroxide, bee defensin-1, high osmolarity and low value of pH seems to be crucial for its antimicrobial potential. Considering honey as a therapeutic, antimicrobial agent special attention deserves Manuka honey. Its high antimicrobial activity is caused by high concentration of 1,2-dicarbonyl compound methylglyoxal. Some authors also suggest that other phytochemicals, especially phenolic compounds, are important antibacterial ingredients of honey. The results of many in vitro but also in vivo studies confirm high antimicrobial potential of honey against some important human and veterinary pathogens: Staphylococcus aureus, Helicobacter pylori, Mycobacterium tuberculosis, Pseudomonas aeruginosa and Escherichia coli. We do not have doubts that honey, but also other bee products, especially propolis, is promising antimicrobial agents and possibilities of their application in clinical medicine deserve consideration.",book:{id:"5520",slug:"honey-analysis",title:"Honey Analysis",fullTitle:"Honey Analysis"},signatures:"Piotr Szweda",authors:[{id:"117528",title:"Dr.",name:"Szweda",middleName:null,surname:"Piotr",slug:"szweda-piotr",fullName:"Szweda Piotr"}]},{id:"54195",doi:"10.5772/67262",title:"Microorganisms in Honey",slug:"microorganisms-in-honey",totalDownloads:3960,totalCrossrefCites:12,totalDimensionsCites:20,abstract:"Honey is a product with low water activity because of the great amount of sugars (fructose and glucose), and also it has antimicrobial compounds derived from flowers or because of its transformation process in the beehive. Despite all the honey microorganism barriers, some species of microorganisms are able to survive and may cause damage to honeybees or consumers. Techniques of pathogenic microorganism identification by DNA using PCR are recommended and required for sanitary and customs control. It is important to know the diversity of contaminating microorganisms in honey, especially due to disseminate pathogenic microorganisms in the international traded marketing. In contrast, beneficial microorganisms such as yeasts can remain latently in this product waiting for the moment in which the environment is suitable for their development. Among the beneficial bacteria found in honeybee products, we can mention some lactic acid bacteria that act as prebiotics when ingested. The microorganisms in the digestive tract of honeybees are important for their health. Thus, we present the knowledge of microbiota associated with honey from honeybees and stingless bees (Hymenoptera, Apidae) and the techniques available for the detection of microorganisms in honey.",book:{id:"5520",slug:"honey-analysis",title:"Honey Analysis",fullTitle:"Honey Analysis"},signatures:"Mayara Salgado Silva, Yavor Rabadzhiev, Monique Renon Eller, Ilia\nIliev, Iskra Ivanova and Weyder Cristiano Santana",authors:[{id:"192986",title:"Dr.",name:"Weyder Cristiano",middleName:null,surname:"Santana",slug:"weyder-cristiano-santana",fullName:"Weyder Cristiano Santana"},{id:"197594",title:"MSc.",name:"Mayara",middleName:null,surname:"Salgado-Silva",slug:"mayara-salgado-silva",fullName:"Mayara Salgado-Silva"},{id:"197595",title:"Dr.",name:"Yavor",middleName:null,surname:"Rabadzhiev",slug:"yavor-rabadzhiev",fullName:"Yavor Rabadzhiev"},{id:"197596",title:"Prof.",name:"Monique",middleName:null,surname:"Eller",slug:"monique-eller",fullName:"Monique Eller"},{id:"197597",title:"Prof.",name:"Iskra",middleName:null,surname:"Ivanova",slug:"iskra-ivanova",fullName:"Iskra Ivanova"},{id:"197598",title:"Prof.",name:"Ilia",middleName:null,surname:"Iliev",slug:"ilia-iliev",fullName:"Ilia Iliev"}]},{id:"53469",doi:"10.5772/66839",title:"Techniques for the Evaluation of Physicochemical Quality and Bioactive Compounds in Honey",slug:"techniques-for-the-evaluation-of-physicochemical-quality-and-bioactive-compounds-in-honey",totalDownloads:3850,totalCrossrefCites:8,totalDimensionsCites:17,abstract:"Honey is a concentrated aqueous solution of sugar, especially glucose and fructose, and minor amounts of dextrin, enzymes, waxes, volatile oils, organic acids, ethers, albuminoidal gum substances and minerals. Commercially available honey samples vary in quality according to various factors such as climate diversity, type of flora of the surrounding region, geographical characteristics, processing, floral supply period, and packaging and storage conditions, which can compromise the standardization and quality of the final product. The different techniques that will be presented in this chapter to assess the quality of honey are tests required by identification standards and national and international quality control or are important quality tools that can be used in the evaluation of the conditions for obtaining and processing of the honey, fraud identification and changes to and/or adulteration of the honey, ensuring the physical and chemical composition of the project and guaranteeing quality standards, directly impacting the shelf life and use and presentation of the product.",book:{id:"5520",slug:"honey-analysis",title:"Honey Analysis",fullTitle:"Honey Analysis"},signatures:"Maria Josiane Sereia, Paulo Henrique Março, Marcia Regina Geraldo\nPerdoncini, Rejane Stubs Parpinelli, Erica Gomes de Lima and\nFernando Antônio Anjo",authors:[{id:"192188",title:"Dr.",name:"Maria",middleName:null,surname:"Sereia",slug:"maria-sereia",fullName:"Maria Sereia"}]},{id:"53417",doi:"10.5772/66590",title:"Production and Trade of Honey in Selected European Countries: Serbia, Romania and Italy",slug:"production-and-trade-of-honey-in-selected-european-countries-serbia-romania-and-italy",totalDownloads:2182,totalCrossrefCites:3,totalDimensionsCites:10,abstract:"The beekeeping sector is very complex, because of not onlythe diversity of bee products obtained but also the environmental services through pollination. Even if its direct impact on domestic economy and trade varies across countries, at micro-level, beekeeping creates well-being for communities, providing health products for population and decent revenues for farmers. It also supports the sustainability of rural livelihoods. In this context, the research subject is the analysis of production and trade of honey in three European Union Countries—Romania, Italy and Serbia—with a goal to consider the dynamic of supply and trade of honey and deduce potential opportunities for producers. The goal of the study is to draw implication from the results obtained, suggesting the concrete measures to improve the existing situation. Trade data are examined to get a picture of honey sector trends. An entire set of trade indicators related to honey were computed over the period 2006–2015 and are presented in the chapter: value, amount, growth rate and geographic structure of export and import in the world and in selected countries for which the level of comparative advantages of exported honey was also measured using the Balassa index.",book:{id:"5520",slug:"honey-analysis",title:"Honey Analysis",fullTitle:"Honey Analysis"},signatures:"Cristina Bianca Pocol, Svetlana Ignjatijević and Daniele Cavicchioli",authors:[{id:"190657",title:"Dr.",name:"Svetlana",middleName:null,surname:"Ignjatijević",slug:"svetlana-ignjatijevic",fullName:"Svetlana Ignjatijević"},{id:"192970",title:"Associate Prof.",name:"Cristina Bianca",middleName:null,surname:"Pocol",slug:"cristina-bianca-pocol",fullName:"Cristina Bianca Pocol"},{id:"192971",title:"Dr.",name:"Daniele",middleName:null,surname:"Cavicchioli",slug:"daniele-cavicchioli",fullName:"Daniele Cavicchioli"}]},{id:"53775",doi:"10.5772/67020",title:"Honey as a Functional Food",slug:"honey-as-a-functional-food",totalDownloads:2192,totalCrossrefCites:5,totalDimensionsCites:10,abstract:"The most well‐known functional properties of honey are its antioxidant and antimicrobial activities. The bioactive components of honey are affected by the flora from which it is produced and by geographical variations. Phenolic compounds promote, among other activities, high antioxidant action, being capable of minimizing intracellular oxidative damage associated with cellular aging, apoptosis and neurodegenerative diseases. A living cell system would provide a better platform for determining antioxidant activity, since the bioactive honey compounds can act modulating antioxidant defense gene expression. Indeed, phenolic compounds, amino acids and reducing sugars are among the substances responsible for honey antioxidant activity. Most of phenolic compounds also exert antimicrobial activity against a number of pathogens and spoilage microorganisms. The antimicrobial activity of honey is also due to the action of enzymes. In addition, honey was found to contain lactic acid bacteria (LAB), which itself produce a myriad of active compounds that remain in variable amounts in mature honey. In addition, these antioxidant compounds might play a key role as prebiotic, protecting and stimulating growth of probiotic bacteria. Oligosaccharides present in honey are well‐known prebiotic substances stimulating growth, activity and protecting probiotic bacteria during passage through the gastrointestinal tract and during storage of the products. This chapter describes the main bioactive components of honey, especially with respect to the phenolic compounds and their antioxidant activity and assay methods.",book:{id:"5520",slug:"honey-analysis",title:"Honey Analysis",fullTitle:"Honey Analysis"},signatures:"Rosa Helena Luchese, Edlene Ribeiro Prudêncio and André\nFioravante Guerra",authors:[{id:"191671",title:"Ph.D.",name:"Rosa",middleName:null,surname:"Luchese",slug:"rosa-luchese",fullName:"Rosa Luchese"},{id:"192130",title:"MSc.",name:"Edlene",middleName:null,surname:"Prudêncio",slug:"edlene-prudencio",fullName:"Edlene Prudêncio"},{id:"192133",title:"MSc.",name:"André",middleName:null,surname:"Guerra",slug:"andre-guerra",fullName:"André Guerra"}]}],mostDownloadedChaptersLast30Days:[{id:"54003",title:"Antimicrobial Activity of Honey",slug:"antimicrobial-activity-of-honey",totalDownloads:4356,totalCrossrefCites:10,totalDimensionsCites:24,abstract:"Honey has had a valued place in traditional medicine for centuries. It was used to overcome liver, cardiovascular and gastrointestinal problems and for treatment of some types of infectious disease. Particularly, good results were achieved in the case of application of this product for therapy of infected, difficult to heal wounds. The high health-promoting properties of honey have been recently confirmed in many research investigations. The antimicrobial activity of this product is highly complex. Generation of hydrogen peroxide, bee defensin-1, high osmolarity and low value of pH seems to be crucial for its antimicrobial potential. Considering honey as a therapeutic, antimicrobial agent special attention deserves Manuka honey. Its high antimicrobial activity is caused by high concentration of 1,2-dicarbonyl compound methylglyoxal. Some authors also suggest that other phytochemicals, especially phenolic compounds, are important antibacterial ingredients of honey. The results of many in vitro but also in vivo studies confirm high antimicrobial potential of honey against some important human and veterinary pathogens: Staphylococcus aureus, Helicobacter pylori, Mycobacterium tuberculosis, Pseudomonas aeruginosa and Escherichia coli. We do not have doubts that honey, but also other bee products, especially propolis, is promising antimicrobial agents and possibilities of their application in clinical medicine deserve consideration.",book:{id:"5520",slug:"honey-analysis",title:"Honey Analysis",fullTitle:"Honey Analysis"},signatures:"Piotr Szweda",authors:[{id:"117528",title:"Dr.",name:"Szweda",middleName:null,surname:"Piotr",slug:"szweda-piotr",fullName:"Szweda Piotr"}]},{id:"53469",title:"Techniques for the Evaluation of Physicochemical Quality and Bioactive Compounds in Honey",slug:"techniques-for-the-evaluation-of-physicochemical-quality-and-bioactive-compounds-in-honey",totalDownloads:3850,totalCrossrefCites:8,totalDimensionsCites:17,abstract:"Honey is a concentrated aqueous solution of sugar, especially glucose and fructose, and minor amounts of dextrin, enzymes, waxes, volatile oils, organic acids, ethers, albuminoidal gum substances and minerals. Commercially available honey samples vary in quality according to various factors such as climate diversity, type of flora of the surrounding region, geographical characteristics, processing, floral supply period, and packaging and storage conditions, which can compromise the standardization and quality of the final product. The different techniques that will be presented in this chapter to assess the quality of honey are tests required by identification standards and national and international quality control or are important quality tools that can be used in the evaluation of the conditions for obtaining and processing of the honey, fraud identification and changes to and/or adulteration of the honey, ensuring the physical and chemical composition of the project and guaranteeing quality standards, directly impacting the shelf life and use and presentation of the product.",book:{id:"5520",slug:"honey-analysis",title:"Honey Analysis",fullTitle:"Honey Analysis"},signatures:"Maria Josiane Sereia, Paulo Henrique Março, Marcia Regina Geraldo\nPerdoncini, Rejane Stubs Parpinelli, Erica Gomes de Lima and\nFernando Antônio Anjo",authors:[{id:"192188",title:"Dr.",name:"Maria",middleName:null,surname:"Sereia",slug:"maria-sereia",fullName:"Maria Sereia"}]},{id:"53175",title:"Analytical Procedures for Determining Heavy Metal Contents in Honey: A Bioindicator of Environmental Pollution",slug:"analytical-procedures-for-determining-heavy-metal-contents-in-honey-a-bioindicator-of-environmental-",totalDownloads:3699,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Metals are pollutant residues detectable in honey and in fact account for most of the inorganic pollutants found in this food product. Metal pollutants can be accumulated through the food chain and, at levels exceeding safe thresholds, can be toxic to humans and even damage physiological functions. During the honey-making process, bees can transport pollutants to the beehive following contact with polluted botanic species or from drinking contaminated water. Detecting very low concentrations is a persisting challenge to accurately measure these elements in honey. Additionally, since honey is a complex organic matrix, treatments are needed prior to applying any classical chemical methods for metal determination, such as inductively coupled plasma and atomic absorption spectroscopy. Therefore, optimal results are dependent on adequate sample conditioning prior to heavy metal content analyses. Chemical pretreatments include calcination processes and/or acid digestion. Regarding execution, the last steps of any metal detection methodology are the primary determinants of result quality, where any loss of mass is reflected by unreliable values.",book:{id:"5520",slug:"honey-analysis",title:"Honey Analysis",fullTitle:"Honey Analysis"},signatures:"Enrique Mejías and Tatiana Garrido",authors:[{id:"191583",title:"Dr.",name:"Enrique",middleName:null,surname:"Mejias",slug:"enrique-mejias",fullName:"Enrique Mejias"},{id:"193079",title:"Dr.",name:"Tatiana",middleName:null,surname:"Garrido",slug:"tatiana-garrido",fullName:"Tatiana Garrido"}]},{id:"53895",title:"Rheological Properties of Honey in a Liquid and Crystallized State",slug:"rheological-properties-of-honey-in-a-liquid-and-crystallized-state",totalDownloads:2360,totalCrossrefCites:4,totalDimensionsCites:6,abstract:"The rheological properties of honey are discussed separately for liquid and crystallized honey. The research methods used in both cases are characterized. The basic mathematical models are shown, which describe the viscosity of honey in its liquid form depending on temperature and water content. In the case of crystallized honey, the rheological properties were linked to morphological features and crystalline phase content. Results of characteristic experiments are presented, obtained during the shearing of crystallized suspension, that is, crystallized honey. Among other items, the dependency of equilibrium stress on shear rate, apparent viscosity on crystalline phase content, hysteresis loops as evidence that honey in its crystallized form is a rheologically unstable fluid. Results of measurements under forced oscillation conditions are included and compared with results of rotational measurements. It was shown that the research method influences the obtained results of rheological studies.",book:{id:"5520",slug:"honey-analysis",title:"Honey Analysis",fullTitle:"Honey Analysis"},signatures:"Sławomir Bakier",authors:[{id:"192064",title:"Ph.D.",name:"Sławomir",middleName:null,surname:"Bakier",slug:"slawomir-bakier",fullName:"Sławomir Bakier"}]},{id:"53417",title:"Production and Trade of Honey in Selected European Countries: Serbia, Romania and Italy",slug:"production-and-trade-of-honey-in-selected-european-countries-serbia-romania-and-italy",totalDownloads:2182,totalCrossrefCites:3,totalDimensionsCites:10,abstract:"The beekeeping sector is very complex, because of not onlythe diversity of bee products obtained but also the environmental services through pollination. Even if its direct impact on domestic economy and trade varies across countries, at micro-level, beekeeping creates well-being for communities, providing health products for population and decent revenues for farmers. It also supports the sustainability of rural livelihoods. In this context, the research subject is the analysis of production and trade of honey in three European Union Countries—Romania, Italy and Serbia—with a goal to consider the dynamic of supply and trade of honey and deduce potential opportunities for producers. The goal of the study is to draw implication from the results obtained, suggesting the concrete measures to improve the existing situation. Trade data are examined to get a picture of honey sector trends. An entire set of trade indicators related to honey were computed over the period 2006–2015 and are presented in the chapter: value, amount, growth rate and geographic structure of export and import in the world and in selected countries for which the level of comparative advantages of exported honey was also measured using the Balassa index.",book:{id:"5520",slug:"honey-analysis",title:"Honey Analysis",fullTitle:"Honey Analysis"},signatures:"Cristina Bianca Pocol, Svetlana Ignjatijević and Daniele Cavicchioli",authors:[{id:"190657",title:"Dr.",name:"Svetlana",middleName:null,surname:"Ignjatijević",slug:"svetlana-ignjatijevic",fullName:"Svetlana Ignjatijević"},{id:"192970",title:"Associate Prof.",name:"Cristina Bianca",middleName:null,surname:"Pocol",slug:"cristina-bianca-pocol",fullName:"Cristina Bianca Pocol"},{id:"192971",title:"Dr.",name:"Daniele",middleName:null,surname:"Cavicchioli",slug:"daniele-cavicchioli",fullName:"Daniele Cavicchioli"}]}],onlineFirstChaptersFilter:{topicId:"346",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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",coverUrl:"https://cdn.intechopen.com/series/covers/23.jpg",latestPublicationDate:"June 25th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"280770",title:"Dr.",name:"Katherine K.M.",middleName:null,surname:"Stavropoulos",slug:"katherine-k.m.-stavropoulos",fullName:"Katherine K.M. Stavropoulos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRdFuQAK/Profile_Picture_2022-05-24T09:03:48.jpg",biography:"Katherine Stavropoulos received her BA in Psychology from Trinity College, in Connecticut, USA. Dr. Stavropoulos received her Ph.D. in Experimental Psychology from the University of California, San Diego. She completed her postdoctoral work at the Yale Child Study Center with Dr. James McPartland. Dr. Stavropoulos’ doctoral dissertation explored neural correlates of reward anticipation to social versus nonsocial stimuli in children with and without autism spectrum disorders (ASD). She has been a faculty member at the University of California, Riverside in the School of Education since 2016. Her research focuses on translational studies to explore the reward system in ASD, as well as how anxiety contributes to social challenges in ASD. She also investigates how behavioral interventions affect neural activity, behavior, and school performance in children with ASD. She is also involved in the diagnosis of children with ASD and is a licensed clinical psychologist in California. 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He graduated from the Physics Department of the University of Crete and continued his post-graduate studies at the University Paris 7-Denis Diderot (D.E.A. in Didactic of Physics), University Paris 5-René Descartes-Sorbonne (D.E.A. in Science Education) and received his Ph.D. degree at the University Paris 5-René Descartes-Sorbonne (PhD in Science Education). His research interests include science education in early childhood, science teaching and learning, e-learning, the use of ICT in science education, games simulations, and mobile learning. 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She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education. She also has the experience of participating in five Erasmus+ projects.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorThree:null},{id:"90",title:"Human Development",coverUrl:"https://cdn.intechopen.com/series_topics/covers/90.jpg",isOpenForSubmission:!0,annualVolume:11974,editor:{id:"191040",title:"Dr.",name:"Tal",middleName:null,surname:"Dotan Ben-Soussan",slug:"tal-dotan-ben-soussan",fullName:"Tal Dotan Ben-Soussan",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBf1QAG/Profile_Picture_2022-03-18T07:56:11.jpg",biography:"Tal Dotan Ben-Soussan, Ph.D., is the director of the Research Institute for Neuroscience, Education and Didactics (RINED) – Paoletti Foundation. 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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. 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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. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}]},{type:"book",id:"7839",title:"Malaria",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7839.jpg",slug:"malaria",publishedDate:"December 11th 2019",editedByType:"Edited by",bookSignature:"Fyson H. Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",biography:"Dr. Kasenga is a graduate of Tumaini University, Kilimanjaro Christian Medical College, Moshi, Tanzania and Umeå University, Sweden. He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). 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Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. 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Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}}]}},subseries:{item:{id:"11",type:"subseries",title:"Cell Physiology",keywords:"Neurodevelopment and Neurodevelopmental Disease, Free Radicals, Tumor Metastasis, Antioxidants, Essential Fatty Acids, Melatonin, Lipid Peroxidation Products and Aging Physiology",scope:"\r\n\tThe integration of tissues and organs throughout the mammalian body, as well as the expression, structure, and function of molecular and cellular components, is essential for modern physiology. The following concerns will be addressed in this Cell Physiology subject, which will consider all organ systems (e.g., brain, heart, lung, liver; gut, kidney, eye) and their interactions: (1) Neurodevelopment and Neurodevelopmental Disease (2) Free Radicals (3) Tumor Metastasis (4) Antioxidants (5) Essential Fatty Acids (6) Melatonin and (7) Lipid Peroxidation Products and Aging Physiology.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11407,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null,series:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261"},editorialBoard:[{id:"186048",title:"Prof.",name:"Ines",middleName:null,surname:"Drenjančević",slug:"ines-drenjancevic",fullName:"Ines Drenjančević",profilePictureURL:"https://mts.intechopen.com/storage/users/186048/images/5818_n.jpg",institutionString:null,institution:{name:"University of Osijek",institutionURL:null,country:{name:"Croatia"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"79615",title:"Dr.",name:"Robson",middleName:null,surname:"Faria",slug:"robson-faria",fullName:"Robson Faria",profilePictureURL:"https://mts.intechopen.com/storage/users/79615/images/system/79615.png",institutionString:null,institution:{name:"Oswaldo Cruz Foundation",institutionURL:null,country:{name:"Brazil"}}},{id:"84459",title:"Prof.",name:"Valerie",middleName:null,surname:"Chappe",slug:"valerie-chappe",fullName:"Valerie Chappe",profilePictureURL:"https://mts.intechopen.com/storage/users/84459/images/system/84459.jpg",institutionString:null,institution:{name:"Dalhousie University",institutionURL:null,country:{name:"Canada"}}}]},onlineFirstChapters:{paginationCount:26,paginationItems:[{id:"82112",title:"Comparative Senescence and Lifespan",doi:"10.5772/intechopen.105137",signatures:"Hassan M. 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