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Prof.",name:"George",surname:"Matsopoulos",slug:"george-matsopoulos",fullName:"George Matsopoulos"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"74055",title:"Evidence for the Role of Cell Reprogramming in Naturally Occurring Cardiac Repair",doi:"10.5772/intechopen.94740",slug:"evidence-for-the-role-of-cell-reprogramming-in-naturally-occurring-cardiac-repair",body:'Pulmonary arterial hypertension (PAH) affects males and females of any age, including children. Despite the availability of approved drugs, PAH remains a fatal disease without a cure [1, 2]. The major pathogenic features that increase the pulmonary vascular resistance in PAH include the vasoconstriction and the development of vascular remodeling, in which pulmonary artery (PA) walls are thickened and the lumens are narrowed or occluded. Increased resistance puts strain on the right ventricle (RV), and right heart failure is the major cause of death among PAH patients [3, 4]. The median overall survival for patients diagnosed with PAH is 2.8 years from the time of diagnosis (3-year survival: 48%) if untreated [5, 6]. Even with currently available therapies, the prognosis remains poor with only 58–75% of PAH patients surviving for 3 years [7, 8, 9, 10]. PAH is a progressive disease; and by the time patients are diagnosed, RV damage has often already occurred.
RV failure is the major cause of death among patients with PAH. However, no treatment strategies are available to manage the RV dysfunctions. Physiologically, the RV needs to cope with fold changes in PA pressure. Thus, the RV is capable of adapting to increased pressure. Similarly to human patients with PAH, we found that the RV of Sprague–Dawley (SD) rats treated with SU5416 and hypoxia to produce PAH suffer from severe cardiac fibrosis at 8 to 17 weeks after the initiation of the SU5416/hypoxia treatment [11]. Remarkably, at 35 weeks after the initiation of the SU5416/hypoxia treatment, RV fibrosis was found to be resolved in these rats, despite the RV pressure remained high [12]. Thus, the RV remodeling can naturally be reversed in these animals, providing an interesting model of RV repair. Understanding the mechanism of such naturally occurring events should shed a light on developing therapeutic strategies to repair the cardiac damage in human patients. The present study examined the mechanism of this cardiac repair process.
Male adult SD rats (Charles River Laboratories International, Inc., Wilmington, MA, USA) were subcutaneously injected with SU5416 (20 mg/kg body weight; MedChem Express, Monmouth Junction, NJ, USA), maintained in hypoxia for 3 weeks [11, 12] and then in normoxia for up to 32 weeks (35-week time points). Animals were subjected to hypoxia in a chamber (30”w x 20”d x 20”h) regulated by an OxyCycler Oxygen Profile Controller (Model A84XOV; BioSpherix, Redfield, NY, USA) set to maintain 10% O2 with an influx of N2 gas, located in the animal care facility at the Georgetown University Medical Center [11, 12]. Ventilation to the outside of the chamber was adjusted to remove CO2, such that its level did not exceed 5000 ppm. Control animals were subjected to ambient 21% O2 (normoxia) in another chamber. Animals were fed normal rat chow. Animals were anesthetized and euthanized by excising the heart and the lungs.
The Georgetown University Animal Care and Use Committee approved all animal experiments, and the investigation conformed to the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals.
RV tissues were immersed in buffered 10% formalin at room temperature, and were embedded in paraffin. These paraffin-embedded tissues were cut and mounted on glass slides. IHC was performed using horseradish peroxidase (HRP) labeled polymer and 3,3′-diaminobenzidine (DAB) chromagen (Agilent Technologies, Santa Clara, CA, USA) with α-smooth muscle actin (αSMA; Catalog # ab32575) and Sox2 (Catalog # ab97959) antibodies (Abcam, Cambridge, UK).
The RV free wall tissues of rats subjected to SU5416/hypoxia as well as cultured cardiomyocytes derived from human induced pluripotent stem cells (iPSCs) purchased from Cell Applications, Inc. (San Diego, CA) were fixed in the 2.5% glutaraldehyde/0.05 M cacodylate solution, post-fixed with 1% osmium tetroxide and embedded in EmBed812. Ultrathin sections (70 nm) were post-stained with uranyl acetate and lead citrate and examined in the Talos F200X FEG transmission electron microscope (FEI, Hillsboro, OR, USA) at 80 KV located at the George Washington University Nanofabrication and Imaging Center. Digital electron micrographs were recorded with the TIA software (FEI).
Means and standard errors were calculated. Comparisons between three groups were analyzed by using one-way analysis of variance (ANOVA) with a Student–Newman–Keuls post-hoc test using the GraphPad Prism (GraphPad Software, Inc., La Jolla, CA, USA). P < 0.05 was considered to be significant.
Since the initial discovery that treating SD rats with the SU5416 injection plus chronic hypoxia promoted severe PAH with pulmonary vascular lesions that resemble those of human patients [13], this experimental model has become a gold standard in the research field of PAH. Experimental design usually involves the single subcutaneous injection of SU5416, followed by subjecting to chronic hypoxia for 3 weeks. In many studies, rats are then maintained in normoxia for 2 to 5 weeks, and PAH and pulmonary vascular remodeling are observed [13, 14, 15, 16, 17]. At this stage, some laboratories including ours have reported that the RV is severely damaged with fibrosis [11, 14, 18, 19]. At 8 to 17 weeks after the SU5416 injection, however, we found that, despite the occurrence of severe fibrosis, the RV contractility is maintained or even improved, perhaps due to the formation of ‘super’ RV myocytes [11]. Moreover, our more recent results demonstrated that, at 35 weeks (3 weeks hypoxia followed by 32 weeks of normoxia), RV fibrosis was largely resolved, despite the RV pressure remained high [12]. The number of myofibroblasts that contribute to the formation of fibrosis, as detected using a well utilized marker αSMA, is increased in non-vessel regions of the RV of SD rats with severe PAH as well as RV fibrosis, and this expression declined in rats with repaired RV at 35 week after the SU5416 injection [12]. Thus, the SU5416/hypoxia treatment does not cause the death of SD rats and the damaged RV can be repaired naturally. Since RV myocytes were not hypertrophied at 35-weeks, the number of myocytes must have been increased to fill the post-fibrotic areas. Indeed counting cardiomyocytes indicated that, compared to the 17-week time point when fibrosis was present, the number of cardiomyocytes increased at 35-weeks when the RV was repaired (Figure 1).
Restoration of RV cardiomyocytes. SU5416-injected SD rats were subjected to 3 weeks hypoxia and then maintained in normoxia to promote PAH. 17 and 35 weeks after the SU5416 injection, RV myocardium tissues were fixed in formalin, embedded in paraffin, and subjected to H&E staining. The number of cardiomyocytes were counted and expressed as % of the control rats (Cont). SD rats with PAH at 17 weeks after the initiation of SU5416/hypoxia had significantly reduced RV myocyte number compared to healthy controls. This decrease in RV myocyte number was restored at 35 weeks. The symbol * denotes that the values are significantly different from each other at p < 0.05.
Based on these results, we hypothesize that these SD rats possess a mechanism that repairs the damaged heart in response to PAH. This raises a question on where regenerated cardiomyocytes come from when the RV repair occurs. It is now known that some adult cardiomyocytes are capable of proliferating [20]. However, the cardiac renewal through the cardiomyocyte proliferation would be too slow to replace large fibrotic areas that were seen in our experimental model. Another possibility is that new cardiomyocytes were regenerated from cardiac progenitor cells. We have identified c-kit and isl1-positive cardiac progenitor cells in the RV of SD rats, however, their levels were not altered in PAH rats (data not shown).
Our previous experiments described in Zungu-Edmondson et al. [12] using the αSMA antibody were originally performed for the purpose of detecting myofibroblasts, which express αSMA. By examining αSMA IHC slides from RVs of SD rats with PAH (at 17-weeks) with a larger magnification (x1,000) as shown in Figure 2A of Zungu-Edmondson et al. [12], we noticed that some brown αSMA stains, in addition to myofibroblasts indicated by arrows, also occurred on cardiomyocytes. We initially discarded these observations by thinking that they are non-specific artifacts. However, further examinations of a number of IHC slides made us convinced that cardiomyocytes are indeed stained with the αSMA antibody. This seems to occur regionally as a group in the myocardial walls (Figure 2A). Figure 2B shows the amplified view of Figure 2A clearly demonstrating that these cardiomyocytes with clear striations express αSMA. By contrast, control RVs from healthy rats without PAH did not exhibit the staining of cardiomyocytes with the αSMA antibody (Figure 2C).
Discovery of naturally-occurring induced cardiomyocytes (iCMs)? SU5416-injected SD rats were subjected to 3 weeks hypoxia and then maintained in normoxia to promote PAH. 17 weeks after the injection, myocardium tissues were fixed in formalin, embedded in paraffin, and subjected to IHC using the antibody against αSMA (brown stains). (A and B) αSMA IHC results shown at x200 and x1,000 magnifications, which clearly show the brown stains in RV cardiomyocytes of SD rats with PAH. (C) This brown αSMA stain was not observed in control rat RVs without PAH. Scale bars indicate 200 μm for x200 and 50 μm for x1,000.
Cell reprogramming is defined as the conversion of one specific cell type to another. This technology has gained considerable attention when Prof. Shinya Yamanaka discovered the means to convert fibroblasts into iPSCs and received the Nobel Prize [21]. In their study, stem cell-related transcription factors including Oct4 and Sox2 were used to convert somatic cells to pluripotent cells that can be differentiated into various cell types including cardiomyocytes [22]. More recently, a combination of cardiac-specific transcription factors was found to directly convert fibroblasts into cardiomyocytes [23, 24]. Figure 3A shows our TEM study of cardiomyocytes derived from iPSCs. These induced cardiomyocytes (iCMs) are capable of beating, express contractile proteins, and exhibit an organized sarcomere structure with clear striations and Z-lines (Figure 3A). In addition, some regions with the not well-defined sarcomere organization, which could be in the process of maturing into iCMs were also identified in these TEM images (Figure 3B). iCMs have been shown to express αSMA [25], while normal adult cardiomyocytes do not. Thus, αSMA-positive cardiomyocytes we observed in adult SD rats with PAH could be iCM-like cells. Consistently with this hypothesis, our examination of TEM images revealed that the structure resembling cardiomyocytes maturing from iPSCs as observed in cultured cells (Figure 3B) also occurs in the RV of SD rats with PAH (Figure 4B).
TEM image of cardiomyocytes derived from iPSCs. The reprogramming technology was used to convert cultured human fibroblasts into iPSCs, then to cardiomyocytes (cell applications, Inc.). Fixed iPSC-derived cardiomyocytes were observed under a transmission electron microscope. (A) the representative image shows cardiomyocytes with clear striations and sarcomere structures (arrow), indicating that iPSCs indeed can become matured cardiomyocytes. Magnification, x5,500. (B) we also identified some regions with the not well defined sarcomere organization (arrows), which may be in the process of maturing into cardiomyocytes. Magnification, x14,000.
TEM identification of maturing ICM-like cells in the RV of PAH rats. SD rats were injected with SU5416, subjected to 3 weeks hypoxia, and maintained in normoxia. 20 weeks after the injection, RV tissues were fixed and analyzed by TEM. (A) the image shows normal cardiomyocytes with clear striations and sarcomere structures (arrow). Magnification, x5,500. (B) we also identified some regions with the not well defined sarcomere organization (arrows), which may be in the process of maturing into iCMs, similar to the structure shown in
These results would support the concept that RVs of SD rats with PAH have iCMs-like cells that are produced via cell reprogramming. However, the αSMA expression can be induced by the fetal gene program mechanism that is associated with cardiac hypertrophy, independent of cell reprogramming. Thus, we examined if factors more directly related to cell reprogramming are expressed in these cardiomyocytes. We found that cardiomyocytes of RV tissues from SD rats with PAH also express Sox2 (Figure 5A and B), a stem cell-related transcription factor that has been used to generate iPSCs [22]. By contrast, no Sox2 stains were observed in healthy control SD rats without PAH (Figure 5C).
Expression of Sox2. SU5416-injected SD rats were subjected to 3 weeks hypoxia and then maintained in normoxia to promote PAH. 17 weeks after the injection, hearts were fixed and subjected to IHC with the antibody against Sox2 (brown stains). (A and B) Sox2 IHC results shown at x200 and at x1,000 magnifications, which clearly show the brown stains in RV cardiomyocytes of SD rats with PAH. (C) This brown Sox2 stain was not observed in control rat RVs without PAH. Scale bars indicate 200 μm for x200 and 50 μm for x1,000.
In response to pressure overload, the heart ventricles undergo a series of adaptive events. In response to systemic and pulmonary hypertension, the left ventricle (LV) and the RV, respectively hypertrophy in order to increase the force of muscle contraction. Concentric hypertrophy is the first change that occurs in response to chronic pressure overload, and this compensatory mechanism allows for improved cardiac output. Exercise-induced cardiac hypertrophy, for example, increases the force of contraction in accordance the needs associated with strenuous exercise and training. This adaptive feature is reversible. However, in chronic disease conditions, this compensatory mechanism thickens the ventricular wall too much in a manner that decreases the stroke volume and thus the cardiac output. This results in the second adaptation to decrease the ventricular wall thickness. In case of the LV, the transition from concentric to eccentric hypertrophy predominates, resulting in the dilated LV with the thin ventricular wall. This event, however, does not seem to occur in the RV in response to chronic pulmonary hypertension and the hallmark of cor pulmonale is that the RV myocytes remain concentrically hypertrophied at the time of heart failure. In the RV, the attempt to decrease the RV wall thickness is expected to be related to the promotion of cell death, although it is unclear whether apoptosis really occurs in the RV of human patients with pulmonary hypertension [26]. However, apoptotic cardiomyocytes have been detected in the RV of a rat model of pulmonary hypertension [11]. In these rats, regions of the RV where cardiomyocytes die get filled with fibrosis.
Using well-studied model of PAH, in which SD rats are treated with the SU5416 injection and chronic hypoxia, we previously found that RVs were capable of maintaining sufficient force of muscle contraction even severe fibrosis occurred at 8 to 17 weeks after the initiation of the SU5416/hypoxia treatment [11]. We postulated that this is due to the formation of “super RV myocytes” that are capable of eliciting stronger force of contraction via a mechanism involving the downregulation of calsequestrin 2, the major Ca2+-binding protein of the sarcoplasmic reticulum.
Further, remarkably at 35 weeks after the SU5416/hypoxia initiation, these fibrosis regions disappear and are filled with newly formed cardiomyocytes [12]. The present study indeed showed that the number of cardiomyocytes were increased at the 35-week time point, compared to the 17-week time point. This increased number of cardiomyocytes was found to be associated with the production of RV cardiomyocytes that express αSMA and Sox2 as well as the occurrence of the structure visible in TEM that resembles maturing iCMs similar to those observed in cultured cardiomyocytes derived from iPSCs. From these results, we hypothesize that the damaged RV due to PAH can naturally be repaired in SD rats through a mechanism that involves the conversion of resident cardiac fibroblasts into iCMs via cell reprogramming (Figure 6). Our finding also suggests that the nature possesses the ability for maturing iCMs into functional cardiomyocytes that are capable of eliciting strong muscle contraction through a “functionalization” process (Figure 6). Our results so far provided evidence to support this novel mechanism of cardiac regeneration, however, further work is needed to prove this concept.
Scheme depicting our hypothesis. SD rats possess an RV repair mechanism, in which naturally occurring cell reprogramming process converts resident fibroblasts into αSMA-and Sox2-positive induced cardiomyocytes (iCMs). These rats also possess the functionalization mechanism that makes functional cardiomyocytes that can elicit strong muscle contraction.
Understanding of the endogenous means to repair the heart is important, not only to provide basic knowledge of cardiac physiology, but also to develop therapeutic strategies to treat conditions in which cardiomyocytes are damaged. Along with the cardiomyocyte proliferation and the involvement of cardiac progenitor cells, our results suggest a novel mechanism of cardiac regeneration through cell reprogramming. Defining this naturally occurring mechanism should contribute to the development of technologies to convert resident cardiac fibroblasts into cardiomyocytes to save lives.
The present study generated evidence to support a fascinating and novel mechanism of naturally occurring cardiac repair that should be important for the development of effective therapeutic strategies to treat cardiac failure. This novel mechanism involves the conversion of resident cardiac fibroblasts into iCMs through the cell reprogramming process that appears to share events occurring in iPSC biology.
This work was supported in part by the NIH (grant numbers R01HL072844, R21AI142649, R03AG059554, and R03AA026516) to Y.J.S. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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\\n\\nThe Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
\\n\\nOAPF Publishing Options
\\n\\nDuring the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
\\n\\n*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\\n\\nServices included are:
\\n\\nWhat isn't covered by the Open Access Publishing Fee?
\\n\\nIf your manuscript:
\\n\\nYour Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\\n\\nOpen Access Funding
\\n\\nTo explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\\n\\nFor Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\\n\\nAdded Value of Publishing with IntechOpen
\\n\\nChoosing to publish with IntechOpen ensures the following benefits:
\\n\\nBenefits of Publishing with IntechOpen
\\n\\nAs a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 140,000 international scientists and researchers.
\n\nThe Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
\n\nOAPF Publishing Options
\n\nDuring the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
\n\n*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\n\nServices included are:
\n\nWhat isn't covered by the Open Access Publishing Fee?
\n\nIf your manuscript:
\n\nYour Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\nOpen Access Funding
\n\nTo explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\n\nFor Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\nAdded Value of Publishing with IntechOpen
\n\nChoosing to publish with IntechOpen ensures the following benefits:
\n\nBenefits of Publishing with IntechOpen
\n\n\r\n\tThis series will provide a comprehensive overview of recent research trends in business and management, economics, and marketing. Topics will include asset liability management, financial consequences of the financial crisis and covid-19, financial accounting, mergers and acquisitions, management accounting, SMEs, financial markets, corporate finance and governance, managerial technology and innovation, resource management and sustainable development, social entrepreneurship, corporate responsibility, ethics and accountability, microeconomics, labour economics, macroeconomics, public economics, financial economics, econometrics, direct marketing, creative marketing, internet marketing, market planning and forecasting, brand management, market segmentation and targeting and other topics under business and management. This book series will focus on various aspects of business and management whose in-depth understanding is critical for business and company management to function effectively during this uncertain time of financial crisis, Covid-19 pandemic, and military activity in Europe.
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His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. 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