Mangled Extremity Severity Index (MESI).
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\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:"8270",leadTitle:null,fullTitle:"Maternal and Child Health Matters Around the World",title:"Maternal and Child Health Matters Around the World",subtitle:null,reviewType:"peer-reviewed",abstract:"This edited volume, “Maternal and Child Health Matters Around the World”, is a collection of reviewed and relevant research chapters, offering a comprehensive overview of recent developments in the field of medicine. The book comprises single chapters authored by various researchers and edited by an expert active in the medical research area. All chapters are complete in itself but united under a common research study topic. This publication aims at providing a thorough overview of the latest research efforts by international authors on maternal and child health matters around the world, and open new possible research paths for further novel developments.",isbn:"978-1-83968-380-0",printIsbn:"978-1-83968-379-4",pdfIsbn:"978-1-83968-381-7",doi:"10.5772/intechopen.78255",price:119,priceEur:129,priceUsd:155,slug:"maternal-and-child-health-matters-around-the-world",numberOfPages:138,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"970e2fb7930d29a8d805900b86da459f",bookSignature:"Masoud Mohammadnezhad and Nafisa Huq",publishedDate:"September 9th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8270.jpg",numberOfDownloads:4732,numberOfWosCitations:0,numberOfCrossrefCitations:4,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:6,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:10,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 9th 2018",dateEndSecondStepPublish:"May 30th 2018",dateEndThirdStepPublish:"July 29th 2018",dateEndFourthStepPublish:"October 17th 2018",dateEndFifthStepPublish:"December 16th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"257189",title:"Dr.",name:"Masoud",middleName:null,surname:"Mohammadnezhad",slug:"masoud-mohammadnezhad",fullName:"Masoud Mohammadnezhad",profilePictureURL:"https://mts.intechopen.com/storage/users/257189/images/system/257189.JPG",biography:"Dr. Masoud Mohammadnezhad graduated with a MSc in Health\nPromotion from Tarbiat Modares University in Iran in 2002 and\nwas awarded his Ph.D. in Public Health from Flinders University, Australia, in 2014. Dr Mohammadnezhad has more than 15\nyears of experience in teaching undergraduate, postgraduate,\nand MBBS courses in various university settings. He is currently\nteaching a variety of public health courses, along with developing the course outlines, at Fiji National University (FNU), where he is an Associate\nProfessor of Public Health (Health Promotion) in the School of Public Health and\nPrimary Care, along with being the program coordinator for the health promotion discipline. He has published more than 50 articles, seven of which have been\npublished in 2017. He has published more than 70 articles and have also presented\nat more than 60 national and international conferences. He is an editorial board\nmember of several leading international journals, such as Global Health Journal,\nand a reviewer for a number of high quality journals, such as the British Medical\nJournal, BMC Public Health, PLOS ONE, Rural and Remote Health, Health Promotion Journal of Australia, and Journal of Clinical Nursing",institutionString:"Fiji National University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Fiji National University",institutionURL:null,country:{name:"Fiji"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"257180",title:"Dr.",name:"Nafisa",middleName:null,surname:"Huq",slug:"nafisa-huq",fullName:"Nafisa Huq",profilePictureURL:"https://mts.intechopen.com/storage/users/257180/images/14079_n.jpg",biography:"She is an academician and health care professional working in the School of Public Health, Independent University, Bangladesh. Alongside teaching graduate and undergraduate courses, she is responsible to assist in research projects at the university and undertake some administrative duties. Her research interest is in community mental health with a special focus on women and children. Mental health is a significant part of health that influences other aspects of maternal and child health especially with regard to nutrition, self-care, child care and education. She has recently completed field work on a fellowship from the South Asian Hub for Advocacy Research and Education (SHARE) in mental health where she looked into health care seeking behavior of rural women with and without depression. She also works with Mental Health Awareness Training Education and Research (MATERS) Trust where one of the goals is to address persistent disparities in maternal, infant, and child health with a 'life course” perspective to health promotion and disease prevention.",institutionString:"Independent University of Bangladesh",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1132",title:"Health Care",slug:"medicine-public-health-health-care"}],chapters:[{id:"63711",title:"The Interrelation of the Mother’s Health Status with the State of Health of First- and Second-Year-Old Children",doi:"10.5772/intechopen.80754",slug:"the-interrelation-of-the-mother-s-health-status-with-the-state-of-health-of-first-and-second-year-ol",totalDownloads:809,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"We evaluated the state of health of the mother and child at birth, and the probability of the diagnosis of cancelation in the child at the end of the second year of life. The sample consisted of 100 mother-child dyads. The complex assessment of the children’s health status was based on the individual medical records. Mothers filled the questionnaire evaluating the mother’s relation to her child during the first 2 years of life, and the questionnaire aimed at assessing the emotional intelligence level. Almost all the children at birth have one or the other diagnosis. There is a positive connection between the number of the diagnoses in the first- and second-year-old children during their stay in the maternity ward and perinatal pathology factors of the mother. But by the end of the second year of life in 60% of the children, these diagnoses were canceled. The healthier the mother, the more positive the prognosis with regard to the child’s health within the first 2 years of living is. Positive prognosis with regard to the first-year-old children’s health depends upon the acceptance of the child by the mother: the higher the value on the scale of acceptance-nonacceptance is, the better the child’s health is.",signatures:"Elena Nikolaeva and Vera Merenkova",downloadPdfUrl:"/chapter/pdf-download/63711",previewPdfUrl:"/chapter/pdf-preview/63711",authors:[{id:"258781",title:"Prof.",name:"Elena",surname:"Nikolaeva",slug:"elena-nikolaeva",fullName:"Elena Nikolaeva"},{id:"258792",title:"Dr.",name:"Vera",surname:"Merenkova",slug:"vera-merenkova",fullName:"Vera Merenkova"}],corrections:null},{id:"63368",title:"Public Policies for Promotion of Maternal-Infant Health in Brazil: Some Experiences with Adolescent Mothers in São Paulo",doi:"10.5772/intechopen.80832",slug:"public-policies-for-promotion-of-maternal-infant-health-in-brazil-some-experiences-with-adolescent-m",totalDownloads:371,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter introduces and discusses to what extent policies focused on promoting maternal and infant health through public health services are or are not effective in the coverage area. The discussion is based on accounts of adolescents—mothers or still pregnant—and the assistance provided to them and their children through these services. The accounts, which are derived from an independent program of home visits to accompany these adolescents, are complemented by observations made by the visitation team about whether assistance provided by health services promote maternal and infant health and the rights of children and adolescents. To provide context, we present a panorama of current public-health policies and services aimed at mothers and infants in Brazil, as well as some health indicators for this population. Finally, we discuss the possibilities and challenges of promoting the healthy development of mothers and their children in these contexts.",signatures:"Aline Mizutani Gomes and Renato Alves",downloadPdfUrl:"/chapter/pdf-download/63368",previewPdfUrl:"/chapter/pdf-preview/63368",authors:[{id:"259309",title:"Mrs.",name:"Aline",surname:"Mizutani Gomes",slug:"aline-mizutani-gomes",fullName:"Aline Mizutani Gomes"},{id:"259925",title:"Dr.",name:"Renato",surname:"Alves",slug:"renato-alves",fullName:"Renato Alves"}],corrections:null},{id:"68169",title:"Cytokines and Maternal Omega-3 LCPUFAs Supplementation",doi:"10.5772/intechopen.86402",slug:"cytokines-and-maternal-omega-3-lcpufas-supplementation",totalDownloads:719,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Daily supplementation of maternal diet during pregnancy and lactation with a fish oil-enriched dairy product increases the percentage of DHA and other omega-3 (ω-3) long-chain polyunsaturated fatty acids (LCPUFAs) in mothers (placenta, plasma, erythrocyte membranes, and breast milk) and children (plasma and erythrocyte membranes). This supplementation during critical periods such as pregnancy, lactation, and early development of a newborn may influence the levels of certain inflammatory cytokines, reducing pro-inflammatory cytokines and promoting an anti-inflammatory “environment”. In pregnant women who have not received any supplement of omega-3 LCPUFAs, IL-6 plasma levels are higher, while TNF-alpha plasma levels are also higher in their breastfed infant at birth and 2 months thereafter. There could be a relationship between docosahexaenoic acid (DHA) and the concentrations of different cytokines.",signatures:"Yessica Rodriguez-Santana and Luis Peña-Quintana",downloadPdfUrl:"/chapter/pdf-download/68169",previewPdfUrl:"/chapter/pdf-preview/68169",authors:[{id:"286829",title:"Prof.",name:"Luis",surname:"Peña-Quintana",slug:"luis-pena-quintana",fullName:"Luis Peña-Quintana"},{id:"287552",title:"Dr.",name:"Yessica",surname:"Rodriguez-Santana",slug:"yessica-rodriguez-santana",fullName:"Yessica Rodriguez-Santana"}],corrections:null},{id:"68818",title:"Correlates of Caesarean Section Delivery in West Bengal, India: An Analysis Based on DLHS-3",doi:"10.5772/intechopen.88838",slug:"correlates-of-caesarean-section-delivery-in-west-bengal-india-an-analysis-based-on-dlhs-3",totalDownloads:523,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"It has been well recognised that medically unnecessary caesarean section (C-section) delivery could increase morbidity risks for both the mother and her child and also could put strain on both institutional and individual assets mainly in developing countries. The present study tried to assess the variations in C-section delivery rates by women’s background characteristics and to examine the factors associated with C-section delivery in West Bengal—a state of India. Data from the third round of the District Level Household and Facility Survey (DLHS-3) 2007–2008, covering 6447 ever-married women of age 15–49 years, were used. The results reveal that about 12% women delivered their babies by C-section irrespective of place of delivery, but it rose to about 24% in only institutional delivery. It is also found that the rate of C-section delivery was excessively high in private health facilities (55.8%) followed by higher educated women (50.4%) and for health insurance (36.4%), and antenatal care service eight or more times (36%). The results of predicted (adjusted) probability computed from logistic regression reveal that delivery in private health facilities, higher maternal age, lower birth order and higher level of education were the main influential factors of C-section delivery.",signatures:"Rayhan SK and Somdutta Barua",downloadPdfUrl:"/chapter/pdf-download/68818",previewPdfUrl:"/chapter/pdf-preview/68818",authors:[{id:"298976",title:"Mr.",name:"Rayhan",surname:"SK",slug:"rayhan-sk",fullName:"Rayhan SK"},{id:"307673",title:"Ms.",name:"Somdutta",surname:"Barua",slug:"somdutta-barua",fullName:"Somdutta Barua"}],corrections:null},{id:"69689",title:"Safe Childbirth and Motherhood in African Great Lakes Region: External Pelvimetry in Nulliparae and Scheduled Caesarean Section",doi:"10.5772/intechopen.89638",slug:"safe-childbirth-and-motherhood-in-african-great-lakes-region-external-pelvimetry-in-nulliparae-and-s",totalDownloads:563,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The authors have carried out a literature review of targeted relevant research with a focus on two countries of the African Great Lakes Region, i.e. Rwanda and the Democratic Republic of the Congo (DRC). The aim was to find a common thread between nulliparity and timely caesarean section through external clinical pelvimetry. Higher rates of nulliparity and caesarean section were found with poor outcome in terms of foeto-maternal prognosis. External clinical pelvimetry presented in Rwandan and Congolese nulliparae the same characteristics during pregnancy and at delivery: lower average values in comparison with multiparae who never experienced caesarean section; average values significantly lower in women who underwent caesarean than in those who delivered naturally; and a gradual and significant decrease in caesarean section rate as pelvic sizes increased. Cephalopelvic disproportion, the main cause of mechanical dystocia, was associated with significantly lower pelvic average values. On the basis of an appropriate tool to predict cephalopelvic disproportion and taking as an illustration of complication the case of obstetrical fistulas, the authors finally advocate the use of the pelvimeter to screen in time pelvises at higher risk for cephalopelvic disproportion in resource-constrained environment.",signatures:"Jean-Baptiste Kakoma, Xavier Kinenkinda, Fanny Malonga, Joseph Nsambi, Micrette Ngalula, Jeanne Ngoy and Jean Kalibushi",downloadPdfUrl:"/chapter/pdf-download/69689",previewPdfUrl:"/chapter/pdf-preview/69689",authors:[{id:"284753",title:"Prof.",name:"Xavier",surname:"Kinenkinda",slug:"xavier-kinenkinda",fullName:"Xavier Kinenkinda"},{id:"284758",title:"Prof.",name:"Jean-Baptiste",surname:"Kakoma",slug:"jean-baptiste-kakoma",fullName:"Jean-Baptiste Kakoma"},{id:"309783",title:"Prof.",name:"Fanny",surname:"Malonga",slug:"fanny-malonga",fullName:"Fanny Malonga"},{id:"309784",title:"Dr.",name:"Joseph",surname:"Nsambi",slug:"joseph-nsambi",fullName:"Joseph Nsambi"},{id:"309785",title:"Dr.",name:"Micrette",surname:"Ngalula",slug:"micrette-ngalula",fullName:"Micrette Ngalula"},{id:"309787",title:"Dr.",name:"Jeanne",surname:"Ngoy",slug:"jeanne-ngoy",fullName:"Jeanne Ngoy"},{id:"316883",title:"Dr.",name:"Jean",surname:"Kalibushi",slug:"jean-kalibushi",fullName:"Jean Kalibushi"}],corrections:null},{id:"70912",title:"Quality Care for Mothers and Newborns at Birth in Mexico",doi:"10.5772/intechopen.89639",slug:"quality-care-for-mothers-and-newborns-at-birth-in-mexico",totalDownloads:666,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Estimates of the United Nations (UN) consider that in the world 2.5 million neonates died in the last year from preventable causes such as prematurity, complications during childbirth, and infections. Some died because the care they received was of poor quality. The most striking is that 1.7 million newborns could be saved by improving access to quality care for all pregnant women in humanitarian settings, especially those considered as low- and middle-income countries by the World Bank. Neonatal mortality can be considered as a sensitive indicator of the well-being of a population, the degree of development of a country, as well as health conditions in the mother’s environment and the good quality of prenatal and intrapartum care. This will seek the achievement of the Sustainable Development Goals (SDGs) of the United Nations, through universal health coverage (UHC), by 2030. The medical advances that obstetrics has had around history show the interest and importance for the health sector of all countries in the world, the attention of women, especially during the reproductive stage in which it is located at stake the life and health of the human capital of the future. Today, obstetrics is the health science recognized worldwide because it addresses the health of women during the preconception, conception, prenatal, childbirth, postnatal, and postconception stages, as well as the newborn. Every day more progress is made, not only in the increasingly early diagnosis, but also in the care, attention during the months of gestation, and studies and tests to be carried out to have a greater certainty of what happens inside the uterus‑definitely, we are going forward. But the latter is not available to all pregnant women, or in all regions of Mexico, because of the asymmetry in the structure, with imbalance in qualified human resources and technology that detract from this quality of care that is intended. Therefore, we are still reporting preventable maternal deaths and preterm infants, and the interest of this chapter is to show the need, as referred by the World Health Organization (WHO), to improve the quality of care with qualified personnel: obstetricians for women and neonatologists or pediatricians for newborn care.",signatures:"Bonifacio Caballero Noguéz, Roberto Aguli Ruíz Rosas and Ernesto Calderon Cisneros",downloadPdfUrl:"/chapter/pdf-download/70912",previewPdfUrl:"/chapter/pdf-preview/70912",authors:[{id:"306222",title:"Dr.",name:"Bonifacio",surname:"Caballero-Noguez",slug:"bonifacio-caballero-noguez",fullName:"Bonifacio Caballero-Noguez"},{id:"306223",title:"Dr.",name:"Ernesto",surname:"Calderon Cisneros",slug:"ernesto-calderon-cisneros",fullName:"Ernesto Calderon Cisneros"},{id:"309002",title:"Dr.",name:"Roberto Aguli",surname:"Ruíz Rosas",slug:"roberto-aguli-ruiz-rosas",fullName:"Roberto Aguli Ruíz Rosas"}],corrections:null},{id:"64987",title:"Adolescents Romantic Relationship: Dynamics of Parent-Child Relationship from India",doi:"10.5772/intechopen.81634",slug:"adolescents-romantic-relationship-dynamics-of-parent-child-relationship-from-india",totalDownloads:1083,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Increased interest in romantic relationships is central in adolescents’ lives and has long been considered defining features of adolescence. Romantic relationships have significant influence on emotional wellbeing of adolescents. In Indian context, scientific literature on adolescent girls in romantic relationship is very minimal and studies focused upon sexuality-related issues and pre-marital sexual relationship. Due to social and cultural aspects, few adolescent girls who are involved in romantic relationship run away from home. These girls would come under care and protection under many circumstances such as child marriage, teenage pregnancy, sexual abuse, etc. The present study analyses the case reports in understanding the issues of adolescents in RR issues and the process of interventions provided. A total of 50 girls who were in RR were selected for the study Mean age is 16.34 years (SD ± 0.93) with a range of 14–18 years. About 78% were from lower socio economic status. It is important to understand their issues to provide psycho social intervention and facilitate healthy transition to adulthood. This has implication for designing intervention based on development perspective. Always adolescents in romantic relationship are under the conflict over prioritizing between their parents versus their romantic partner, when they forced to choose one.",signatures:"Navaneetham Janardhana and Basavaraj Manjula",downloadPdfUrl:"/chapter/pdf-download/64987",previewPdfUrl:"/chapter/pdf-preview/64987",authors:[{id:"258235",title:"Ph.D.",name:"Navaneetham",surname:"Janardhana",slug:"navaneetham-janardhana",fullName:"Navaneetham Janardhana"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"1673",title:"Evidence Based Medicine",subtitle:"Closer to Patients or Scientists?",isOpenForSubmission:!1,hash:"d767dfe22c65317eab3fd9ff465cb877",slug:"evidence-based-medicine-closer-to-patients-or-scientists-",bookSignature:"Nikolaos M. 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\r\n\tMolecular modeling methods in new drug discovery or 'repurposing' approaches of known approved drugs have gained a very important place in understanding the behavior of complex biological and chemical systems. The integration of experimental methods with computational methods is invaluable both in the development of promising new bioactive compounds and in the molecular characterization of protein-ligand or protein-protein interactions. Molecular docking, in one of these molecular modeling methods, is a unique approach to revealing key interactions in important molecular recognition processes and to accurately predict receptor-ligand binding free energies. Today, the molecular docking method has not only enabled the discovery of new drugs and therapeutic agents but also opened different windows to the submicroscopic world of interacting partner molecules by providing a unique atomistic perspective in the explanation of important intermolecular phenomena.
\r\n\r\n\tThe topics covered in this book are mainly:
\r\n\t1. Emphasizing the unique power of the molecular docking method in new drug discovery;
\r\n\t2. Demonstration of how the molecular docking technique has led to the discovery of new molecules in cancer therapy, proteasome, and STAT3 inhibition, and the treatment of Alzheimer's disease;
\r\n\t3. Underlining the importance of molecular docking-based modeling methods in the various branches of biotechnology
\r\n\tWe hope that this book will be a common point where researchers working in the fields of life sciences and drug development will eventually meet.
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Dr. Istifli previously joined the molecular cytogenetics group at the Max Planck Institute for Molecular Genetics in Berlin, Germany where he contributed experimentally to the identification of four candidate genes (GRIA2, GLRB, NPY1R, and NPY5R).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"179007",title:"Dr.",name:"Erman Salih",middleName:null,surname:"Istifli",slug:"erman-salih-istifli",fullName:"Erman Salih Istifli",profilePictureURL:"https://mts.intechopen.com/storage/users/179007/images/system/179007.JPG",biography:"Dr. Erman Salih İstifli received his Ph.D. from Biology Department of Cukurova University, Insitute of Science and Letter. In his doctoral study, Dr. İstifli focused on the elucidation of the genotoxic and cytotoxic effects of a commonly used anticancer agent (antifolate) on human lymphocytes. During his period of doctoral research, he joined the molecular cytogenetics group at the Max Planck Institute for Molecular Genetics in Berlin, Germany, and he focused there on investigating the molecular cytogenetic causes of some human rare diseases. During these studies, he contributed experimentally to the identification of four candidate genes (GRIA2, GLRB, NPY1R, and NPY5R) responsible for intelligence and obesity. He was assigned as an expert and rapporteur on eight candidate projects in the Marie-Sklodowska Curie-Actions Innovative Training Networks in 2016. In 2017, he completed the online theoretical and practical course 'Introduction to Biology - The Secret of Life', run by the Massachusetts Institute of Technology (MIT) on the edX platform. In April 2019, within the framework of Erasmus+ staff mobility program, he gave seminars on 'DNA microarrays and their use in genotoxicity' at Tirana University in Tirana, Albania. 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The decision-making process is the most critical part directly affecting the outcome. Although several factors such as the general status of the patient, the condition of the limb, and the experience of the surgeon along with the availability of the facilities help greatly determining what to do next, the outcome is mostly unpredictable when it comes to salvaging of an injured or amputated limb.
\nThe decision for salvation should be done only after it is confirmed that the patient has no accompanying life-threatening injuries. Once the patient is stable, then the injured or amputated limb should be examined thoroughly. If the injured part is grossly contaminated, is severely avulsed, or contains vascular injuries at multiple levels, the patient would not benefit from any salvage procedures; moreover, any attempt to salvage the limb might put the patient’s life at risk.
\nThe main concerns in this decision-making process focus on the extent of vascular, skeletal, and soft tissue damage, the presence of shock, and warm ischemia time. However, additional criteria such as age, contamination, and patient-related comorbidities cannot be disregarded. The details of the incident are also of great importance such as when it happened, the time interval between the incident and arrival to the hospital and mechanism of injury. Like in every patient presenting with major trauma, the initial evaluation should include the establishment of a patent airway and optimization of ventilation and blood circulation. After the patient is stabilized, a thorough physical examination should be performed. In patients presenting with mangled extremities, pulsation, skin color and temperature, and capillary return on the distal segment of the involved limb should be checked. If fracture or dislocation of the involved limb is suspected, X-ray or computed tomography images should be obtained. Peripheral nerve examination should be also performed prior to any intervention. Meanwhile, antibiotic therapy should be initiated as soon as possible, especially in case of open fracture, and tetanus prophylaxis must be administered immediately.
\nIn order to be able to evaluate patients with major limb trauma in a more systematic way, several scoring systems have been proposed. The most widely used scoring systems are Mangled Extremity Syndrome Index (MESI); Mangled Extremity Severity Score (MESS); Predictive Salvage Index (PSI); Limb Salvage Index (LSI); Nerve injury, ischemia, soft tissue injury, skeletal injury, shock, age of patient score (NISSSA); and Ganga Hospital Open Injury Severity Scoring (GHOISS) (Tables 1−6).
\nInjury severity score | \n0–25 | \n1 | \n
\n | 25–50 | \n2 | \n
\n | >50 | \n3 | \n
Integument injury | \nGuillotine | \n1 | \n
\n | Crush/burn | \n2 | \n
\n | Avulsion/degloving | \n3 | \n
Nerve injury | \nContusion | \n1 | \n
\n | Transection | \n2 | \n
\n | Avulsion | \n3 | \n
Vascular injury | \nArterial transection | \n1 | \n
\n | Arterial thrombosis | \n2 | \n
\n | Arterial avulsion | \n3 | \n
\n | Vein | \n1 | \n
Bone injury | \nSimple | \n1 | \n
\n | Segmental | \n2 | \n
\n | Segmental comminuted | \n3 | \n
\n | Bone loss <6 cm | \n4 | \n
\n | Articular | \n5 | \n
\n | Articular with bone loss <6 cm | \n6 | \n
Age | \n<40 years | \n0 | \n
\n | 40–50 years | \n1 | \n
\n | 50–60 years | \n2 | \n
\n | >60 years | \n3 | \n
Lag time to operation | \nFor each hour over 6 hours | \n1 | \n
Pre-existing disease | \n\n | 1 | \n
Shock | \n\n | 2 | \n
Mangled Extremity Severity Index (MESI).
Mangled Extremity Syndrome Index (Table 1) was described by Gregory et al. in 1985 [2]. The components of this index are injury severity score, bone, age, integument injury, nerve, lag time to operation, pre-existing disease, and shock. A cutoff score of 20 is considered for amputation.
\nMESS (Table 2) is probably the most commonly used scoring system worldwide for both upper and lower extremity traumas. It was developed by Johansen et al. in 1990 following a retrospective evaluation of patients with lower mangled extremities [3]. The criteria for MESS include age, the presence of shock, warm ischemia time, and skeletal and soft tissue injury. In case the warm ischemia time is longer than 6 hours, the score is doubled. A MESS value equal to or greater than 7 is suggested as highly predictive for amputation.
\nSkeletal and soft tissue injury | \nLow-energy injury | \n1 | \n
\n | Medium-energy injury | \n2 | \n
\n | High-energy injury | \n3 | \n
\n | Very-high-energy injury or above injuries with gross contamination | \n4 | \n
Limb ischemia* | \nNormal perfusion despite reduced or non-palpable pulse | \n1 | \n
\n | Slow capillary refill | \n2 | \n
\n | No capillary refill | \n3 | \n
Shock status | \nSystolic blood pressure > 90 mm Hg | \n0 | \n
\n | Transient hypotension | \n1 | \n
\n | Persistent hypotension | \n2 | \n
Age | \n<30 years | \n0 | \n
\n | 30–50 years | \n1 | \n
\n | >50 years | \n2 | \n
Mangled Extremity Severity Score (MESS).
The score is doubled if the warm ischemia time >6 hours.
In 1987 PSI (Table 3) was proposed by Howe et al. for scoring lower extremities with orthopedic and vascular injury. In their study, they determined the cutoff value for amputation as 8 [4].
\nBone injury | \nMild trauma | \n1 | \n
\n | Moderate trauma | \n2 | \n
\n | Severe trauma | \n3 | \n
Muscle injury | \nMild trauma | \n1 | \n
\n | Moderate trauma | \n2 | \n
\n | Severe trauma | \n3 | \n
Arterial injury | \nSuprapopliteal | \n1 | \n
\n | Popliteal | \n2 | \n
\n | Infrapopliteal | \n3 | \n
Delay to the operating room | \n<6 hours | \n1 | \n
\n | 6–12 hours | \n2 | \n
\n | >12 hours | \n3 | \n
Predictive salvage index (PSI).
LSI (Table 4) was introduced by Russell et al. in 1991 [5]. Unlike the majority of scoring systems, age and the presence of shock are not included in LSI. On the other hand, there are seven evaluation criteria requiring extensive examination which can be only performed intraoperatively. A score of greater than 6 indicates amputation.
\nArtery | \nContusion, intimal tear, partial laceration, or avulsion | \n0 | \n
\n | Occlusion of ≥2 leg vessels, non-palpable pedal pulses | \n1 | \n
\n | Complete occlusion of femoral or all three leg vessels | \n2 | \n
Nerve | \nContusions, stretch injury, minimal clean laceration | \n0 | \n
\n | Partial transection or avulsion of sciatic nerve; complete/partial transection of femoral and peroneal/tibial nerve | \n1 | \n
\n | Complete transection/avulsion of sciatic nerve or both peroneal and tibial nerves | \n2 | \n
Bone | \nClosed fracture in ≤2 sites; open fracture without comminution; closed dislocation without fracture; fibula fracture; open joint without foreign body | \n0 | \n
\n | Closed fracture in at least three sites on same extremity; open fracture with comminution or moderate to large displacement; open joint with foreign body; bone loss <3 cm | \n1 | \n
\n | Bone loss >3 cm; Gustilo type IIIB,C fractures | \n2 | \n
Skin | \nClean laceration or small avulsion injuries with primary repair or first-degree burn | \n0 | \n
\n | Delayed closure due to contamination; wounds requiring skin grafts or flaps; second- and third-degree burns | \n1 | \n
Muscle | \nAvulsion or laceration of a single compartment or single tendon | \n0 | \n
\n | Avulsion or laceration ≥2 compartments or tendons | \n1 | \n
\n | Crush injury | \n2 | \n
Deep vein | \nContusion, partial laceration, or avulsion; complete laceration or avulsion with intact drainage; superficial vein injury | \n0 | \n
\n | Complete laceration, avulsion, or thrombosis without adequate venous drainage | \n1 | \n
Warm ischemia time | \n<6 hours | \n0 | \n
\n | 6–9 hours | \n1 | \n
\n | 9–12 hours | \n2 | \n
\n | 12–15 hours | \n3 | \n
\n | >15 hours | \n4 | \n
Limb salvage index (LSI).
NISSSA score (Table 5) was proposed by McNamara et al. in 1994 [6]. It is a modified version of MESS with the addition of nerve injury. The cutoff value of NISSSA for amputation is 11.
\nNerve | \nSensate | \nNo major nerve injury | \n0 | \n
\n | Dorsal | \nDeep or superficial peroneal nerve injury | \n1 | \n
\n | Plantar partial | \nTibial nerve injury | \n2 | \n
\n | Plantar complete | \nSciatic nerve injury | \n3 | \n
Ischemia* | \nNone | \nGood to fair pulses, no ischemia | \n0 | \n
\n | Mild | \nReduced pulses, perfusion normal | \n1 | \n
\n | Moderate | \nNo pulses, prolonged capillary refill, Doppler pulses present | \n2 | \n
\n | Severe | \nPulseless, cool, ischemic, no Doppler pulses | \n3 | \n
Soft tissue | \nLow | \nMinimal to no contusion, no contamination | \n0 | \n
\n | Medium | \nModerate injury, low-velocity gunshot wound, moderate contamination, minimal crush | \n1 | \n
\n | High | \nModerate crush, deglove, high-velocity gunshot wound, moderate injury requiring flap, considerable contamination | \n2 | \n
\n | Severe | \nMassive crush, farm injury, severe deglove, severe contamination, requires flap | \n3 | \n
Skeletal | \nLow energy | \nSpiral fracture, oblique fracture, no or minimal displacement | \n0 | \n
\n | Medium energy | \nTransverse fracture, minimal comminution, small caliber gunshot wound | \n1 | \n
\n | High energy | \nModerate displacement or comminution, high-velocity gunshot wound, butterfly fragments | \n2 | \n
\n | Severe energy | \nSegmental, severe comminution, bony loss | \n3 | \n
Shock | \nNormotensive | \nBlood pressure normal, always >90 mm Hg systolic | \n0 | \n
\n | Transient hypotension | \nTransient hypotension in field or emergency center | \n1 | \n
\n | Persistent hypotension | \nPersistent hypotension despite fluids | \n2 | \n
Age | \nYoung | \n<30 years | \n0 | \n
\n | Middle | \n30–50 years | \n1 | \n
\n | Old | \n>50 years | \n2 | \n
Nerve injury, ischemia, soft tissue, skeletal injury, shock, age of patient score (NISSSA) [6].
Score doubles with ischemia >6 hours.
The latest scoring system GHOISS was introduced by Rajasekaran et al. in 2006 [1]. The purpose of the authors was to address the paucity of the current scoring systems in tibial injuries without a vascular deficit (Gustilo type IIIB). GHOISS has the maximum number of components when compared with the other scoring systems (Table 6). A score of 14 or below is favored for the salvation of the limb, whereas a score of 17 or above indicates amputation. The scores falling between 14 and 17 indicate “the gray zone.”
\nCovering structures: skin and fascia | \nNot over the fracture | \n1 | \n|
\n | Exposing the fracture | \n2 | \n|
\n | Not over the fracture | \n3 | \n|
\n | Over the fracture | \n4 | \n|
\n | Circumferential wound with skin loss | \n5 | \n|
Skeletal structures: bone and joints | \nTransverse/oblique fracture/butterfly fragment <50% | \n1 | \n|
\n | Large butterfly fragment >50% circumference | \n2 | \n|
\n | Comminution/segmental fractures without bone loss | \n3 | \n|
\n | Bone loss <4 cm | \n4 | \n|
\n | Bone loss >4 cm | \n5 | \n|
Functional tissues: MT and nerve units | \nPartial injury to MT unit | \n1 | \n|
\n | Complete but repairable injury to MT units | \n2 | \n|
\n | Irreparable injury to MT units/partial loss of a compartment/complete injury to posterior tibial nerve | \n3 | \n|
\n | Loss of one compartment of MT units | \n4 | \n|
\n | Loss of ≥2 compartments/subtotal amputation | \n5 | \n|
Comorbid conditions | \nDrug-dependent diabetes mellitus/cardiorespiratory diseases leading to increased anesthetic risk | \n2 | \n|
\n | Sewage or organic contamination/farmyard injuries | \n2 | \n|
\n | Age > 65 years | \n2 | \n|
\n | Injury-debridement interval > 12 hours | \n2 | \n|
\n | Polytrauma involving the chest or abdomen with injury severity score > 25/fat embolism | \n2 | \n|
\n | Hypotension with systolic blood pressure < 90 mmHg at presentation | \n2 | \n|
\n | Another major injury to the same limb/compartment syndrome | \n2 | \n
The scoring systems were developed to provide a systematic therapeutic approach to mangled extremities.
\nby grading the severity of an injury. Like every concept that tries to tidy up a complicated clinical scenario, these systems have advantages and disadvantages. Most of the scoring systems address lower extremity injuries, while there is no scoring system specifically designed for upper extremity [7]. A single scoring system cannot be established for both upper and lower extremities since they differ in terms of the amount of muscle bulk and the availability of vascular supply [8]. The warm ischemia time is the single factor that has a direct impact on the extent of tissue necrosis and ischemia-reperfusion injury. Thus, it is included in all scoring systems, as demonstrated in Table 7.
\n\n | MESI | \nMESS | \nPSI | \nLSI | \nNISSSA | \nGHOISS | \n
---|---|---|---|---|---|---|
✓ | \n✓ | \n\n | \n | ✓ | \n✓ | \n|
Shock | \n✓ | \n✓ | \n\n | \n | ✓ | \n✓ | \n
Warm ischemia time | \n✓ | \n✓ | \n✓ | \n✓ | \n✓ | \n✓ | \n
Bone injury | \n✓ | \n\n | ✓ | \n✓ | \n\n | ✓ | \n
Muscle injury | \n\n | \n | ✓ | \n✓ | \n\n | ✓ | \n
Skin injury | \n✓ | \n\n | \n | ✓ | \n\n | ✓ | \n
Nerve injury | \n✓ | \n\n | \n | ✓ | \n✓ | \n\n |
Deep vein injury | \n\n | \n | \n | ✓ | \n\n | \n |
Skeletal/soft tissue | \n\n | ✓ | \n\n | \n | ✓ | \n\n |
Contamination | \n\n | \n | \n | \n | ✓ | \n✓ | \n
Time to treatment | \n✓ | \n\n | \n | ✓ | \n\n | \n |
Co-morbidity | \n✓ | \n\n | \n | \n | \n | ✓ | \n
Comparison of the components of the scoring systems.
The most commonly used systems for upper extremity injuries are MESI and MESS [8, 9]. It has been suggested that MESI scoring is more reliable than MESS in terms of prediction of amputation in mangled upper extremity injuries [8]. However, in order to calculate the MESI score, a thorough examination must be completed, and all the accompanying injuries must be identified, which is time-consuming and precludes practicality. On the other hand, although MESS was criticized by several authors in terms of its accuracy and predictive value, it can be still used preoperatively in many clinical settings with ease [10, 11]. The advantage of MESS is that its calculation relies on inspection and basic examination and is reproducible.
\nThe severity of muscle and bone injuries in PSI is graded as mild, moderate, and severe. However, the limits differentiating the severity levels from each other were not described well. Hence it is quite confusing how to grade those injuries with PSI. It would also result in a subjective evaluation rather than a systematic and unbiased calculation [12].
\nThe critic regarding NISSSA is that the severity of nerve injury is only based on the plantar surface sensation indicating the integrity of the tibial nerve, which is no more an absolute contraindication for limb salvage [1]. The sensitivity and specificity of NISSSA have also been found controversial [13].
\nGHOISS is the first system to describe “gray zone” clearly meaning the scores between 14 and 17. It has been suggested that the outcome of the injuries in the gray zone is dependent on noninjury factors such as the skill and experience of the surgical team, the availability of facilities, and the patient’s request. GHOISS was reported to be useful in children as well [14]. In their series of 107 patients with type IIIB injury, Rajasekaran et al. have reported that the Ganga hospital score showed higher sensitivity and specificity for predicting amputation; however, as they have mentioned in their article, this must be validated with multicenter trials [1].
\nThe absolute contraindications for limb salvage or in other words absolute indications for amputations are still open for discussion. Although there is no established consensus about this topic, the presence of certain factors may favor amputation over salvage. First of all, if the patient has an accompanying life-threatening injury, salvage procedure must not be attempted, and such situations render the scoring systems invalid. Another critical point is the warm ischemia time. Lange et al. have suggested that a crush injury with warm ischemia time longer than 6 hours is an absolute indication for amputation [7]. However, this cannot be applied to upper extremity injuries, since the upper extremity has less muscle bulk than the lower extremity and thus is less prone to develop ischemic injury [8]. Roessler et al. have put emphasis on the fluid balance and absence of a distal pulse on presentation that they are eventual indicators for amputation [12]; nevertheless, current advancements in both medical and surgical fields have overcome those concerns. Another historical indication for limb amputation was the nonfunctional posterior tibial nerve [7]. But, as the LEAP study group has demonstrated, the loss of plantar sensation is no more an indication for amputation [15]. Advanced age may also be included among the indications for primary amputation [16].
\nAlbeit, these systems have been designed to enable the surgical team to make a decision, they are not 100% predictive of the ultimate outcome (salvage vs. amputation), and they are also not predictive of functional recovery among patients with successful extremity reconstruction [17, 18, 19]. The sensitivity and specificity rates are quite variable, and all the proposed scoring systems were found to be useful only to some extent [20]. Therefore, in addition to the scores calculated with these systems, patients must be evaluated along with injury pattern and pre-existing comorbidities, and the treatment should be planned also according to the patients’ needs and demands. It is also imperative to take the experience and the skills of the microsurgeon into account. The optimal outcome would be achieved with a systematic multidisciplinary approach, availability of facilities, and always considering what is best for the patient. Raising high expectations both for the surgeon and the patient should be avoided. The technical and individual advancements in the microsurgical field cannot be overlooked; nevertheless, extreme attempts for limb salvage may be harmful to the patient. Moreover, it might become a huge burden for both sides in case it results in a nonfunctional extremity or requires secondary amputation. On the other hand, a patient can still prefer a nonfunctional but salvaged extremity, if there is no contraindication for performing salvage procedure. Therefore, patients’ desire should also be considered as an additional subjective criterion during decision-making. In a nutshell, there is no single recommended scoring system either for upper or lower extremity injuries. They should be only utilized as guides during the planning of the treatment.
\nThe decision for amputation should never be regarded as a failure. It would also be wise asking for consultation from more experienced colleagues before making the ultimate decision. It is the experience and the quality of clinical judgment that save the patient at the end of the day. The scoring systems are a collateral aid in this hard decision-making process. Their benefits are limited because they rely on retrospective data in small patient populations, and unfortunately it still seems to be unlikely to design a prospective model. What we can do better is to combine our experience, these proposed scoring systems for better interpretation of the scores, and narrowing the gray zone as much as possible. As Russel et al. put into words, “numbers cannot replace clinical judgment” [5].
\nScoring systems are useful tools in the evaluation of patients with major extremity traumas. However, each patient requires an individual approach and would benefit from the surgeon’s own experience.
\nThe author declares no conflict of interest.
Death is the final fate of cells and organisms and is a normal biological phenomenon in the living world. Cell death plays a crucial role in the development of plants and animals in nature and in maintaining ecological balance [1]. For example, in the developing vertebrate nervous system, as many as half or more of the nerve cells usually die soon after they are formed. In a healthy adult human, billions of cells die every hour in the bone marrow and intestines. So much cell death seems very wasteful, especially when the vast majority of cells are perfectly healthy at the time of suicide.
In general, cell death can be divided into two types: programmed cell death (PCD) and accidental cell death (necrosis) [2]. The former is a controlled process of intracellular death program, also vividly referred to as cellular suicide. The latter is caused by external factors (i.e., injury, infection, etc.). The study of PCD (especially apoptosis) processes has led to a better understanding of the pathogenesis of certain diseases. The 2002 Nobel Prize in Physiology and Medicine was awarded to Britons Sydney Brenner, Jone E. Sulston, and H Robert Horvitz for their discovery of how genes regulate organ growth and programmed cell suicide processes, using the nematode
A coordinated balance between cell proliferation and apoptosis is crucial for normal development and tissue homeostasis. Once this balance is permanently disrupted, normal cells may be transformed into mutant cells whose clonal survival and uncontrolled proliferation may lead to the development of tumors and various other diseases.
Apoptosis is the process of cellular suicide by activating an intracellular death program or by the orderly breakdown of cells from within. The term was first introduced by Kerr J. F. R. in the 1970s and was not accepted by the general public until the 1990s.
Although apoptosis is only one form of Programmed cell death (PCD), it is by far the most common and well-understood form, and, confusingly, biologists often use the terms PCD and apoptosis interchangeably [3].
For a multicellular organism, a highly organized community, cell numbers are tightly regulated not only by controlling the rate of cell division but also by controlling the rate of cell death. Thus, apoptosis is important not only for tissue remodeling and elimination of transitional organs during the development of an organism, but also for the clearance of cellular senescence inactive metabolic organs, such as blood cells and epithelial cells in the digestive system, and cells with damaged or mutated DNA [4, 5, 6]. In a nutshell, apoptosis is an essential mechanism complementary to proliferation to ensure homeostasis in all tissues.
Unlike apoptosis, necrosis is a form of cell injury that leads to the premature death of cells in living tissues due to autolysis, usually caused by stronger external factors such as infection, toxins, or trauma, ultimately resulting in the unregulated of cellular components, always harmful and potentially fatal to the organism [7, 8]. Necrosis usually causes a local inflammatory response. The reason for this is that when nearby macrophages engulf these necrotic cells, they may release microorganisms that destroy the surrounding tissue causing collateral damage and inhibiting the healing process.
Typically, cell death due to necrosis does not follow the apoptotic signaling transduction pathway, but rather various receptors are activated, leading to loss of cell membrane integrity and uncontrolled release of cell death products into the extracellular space. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cell death and usually provides beneficial effects to the organism. A brief comparison of them can be summarized as follows (Figure 1).
Structural change of cells undergoing necrosis and apoptosis.
As mentioned above, necrosis is a form of traumatic cell death caused by acute cellular injury. In contrast, apoptosis is a process of active cellular suicide. Multicellular organisms eliminate mutated, damaged, or unwanted cells by this type of active suicide. Apoptosis plays an important role in tissue sculpting during embryonic development and in the maintenance of tissue homeostasis throughout life [6].
The process has distinct morphological features, including cell rounding and contraction, blebbing and PS externalization of the plasma membrane, cytoplasmic vacuolization including endoplasmic reticulum expansion and cisternae swelling to form vesicles and vacuoles, nuclear condensation, border aggregation or fragmentation, chromatin compaction, pyknosis, and ultimately fragmentation between nucleosomes by endonucleases, resulting in regular DNA degradation and inhibition of protein translation, and ultimately to the eventual rupture of the cell into small spheres surrounded by membranes called apoptotic bodies, which contain “packed” cell contents with an electron cloud density similar to chromatin; and a sub-G1 curve preceding the G1 phase peak is observed in cytometric histogram [9]. Apoptotic bodies can be recognized and digested by phagocytosis of neighboring macrophages through the presence of phosphatidylserine (PS) on their surface [10]. In this way, the apoptotic cells can be rapidly removed by tissue phagocytes through phagocytosis, without releasing harmful substances that can initiate inflammation, which can cause a significant amount of tissue damage. Because apoptotic cells are always rapidly eaten and digested, dead cells are usually rarely seen, even when large numbers of cells die from apoptosis. This may be the reason why biologists once ignored the phenomenon of apoptosis and may still underestimate its extent.
Abnormal apoptosis contributes to many important diseases, including cancer, autoimmune diseases, diabetes, and neurodegenerative diseases. Various types of cellular stress, such as DNA damage or growth factor deprivation, can trigger apoptosis through intrinsic or extrinsic pathways.
Apoptosis can be triggered by both internal stimuli, such as abnormalities in DNA, and external stimuli, such as certain cytokines from different pathways, respectively [11]; or it can be induced by physiological or pathological factors.
Specifically, physiological triggers can include the following two aspects [12]: (1) Direct action of certain hormones and cytokines: for example, glucocorticoids are typical signals of apoptosis in lymphocytes; thyroxine plays an important role in the apoptotic degeneration of tadpoles’ tails; TNF can induce apoptosis in a variety of cells. (2) Indirect effects of certain hormones and cytokines: for example, testosterone deficiency caused by testicular dysplasia can lead to apoptosis of prostate epithelial cells. Inadequate secretion of adrenocorticotropic hormone by the pituitary gland can promote apoptosis of adrenocortical cells, etc.
While pathological triggers usually include the following two aspects: (1) It is generally believed that apoptosis can be induced by many factors that can cause damage to cells, such as stress, radiation, chemical toxins, viral infections, and chemotherapeutic drugs, and even malnutrition and excessive functional complexes can induce apoptosis. (2) Some factors such as various chemical carcinogens and certain viruses (e.g., EBV) inhibit apoptosis. Therefore, it is thought that the ability to induce cells may be related to the type, intensity, and duration of the harmful factors.
The initiation of apoptosis is tightly regulated by different signaling pathways. The best-understood two are the intrinsic pathway (also known as the mitochondrial pathway) and the extrinsic pathway (also known as the death receptor pathway). The mitochondrial pathway is generally activated by intracellular signals and depends on proteins released from the intermembrane space between the mitochondrial bilayers. The death receptor pathway is activated by extracellular ligands, and the activated extracellular ligands bind to their specific death receptors on the cell surface, inducing the formation of death-inducing signaling complexes (DISC) [13, 14]. Here, we will discuss the extrinsic and intrinsic pathways separately. However, it should be noted that there is crosstalk between these pathways and that extracellular apoptotic signaling can also lead to activation of the intrinsic pathway.
The extrinsic death pathway triggers receptor-mediated apoptosis. Its major components include pro-apoptotic ligands, receptors that recognize/bind ligands, and adaptor proteins that bind to the cytoplasmic face of the receptor. In addition, the pathway recruits other molecules, including cysteine-specific proteases (caspases), the initiator of the death process, and the executors, to execute the apoptotic process [15]. For example, TNF is a common pro-apoptotic ligand and TNFR1 on the cell membrane is the receptor. When TNF binds to TNFR1, the activated receptor binds to two different cytoplasmic adaptor proteins (tumor necrosis factor-related death domain protein, TRADD, and fas-associating protein with death domain, FADD) and procaspase-8, forming a multi-protein complex on the inner surface of the plasma membrane, containing an 80 amino acid death structure domain through which a death-inducing signaling complex (DISC). The cytoplasmic structural domains of the TNF receptor, FADD, and TRADD interact through homologous regions called death structural domains present in each protein [16]. Procaspase-8 and FADD interact through homologous regions called death effector domains. Procaspase 8 in DISC is activated and active caspase 8 is released into the cytoplasm, where it cleaves and activates effector caspases (e.g., procaspase 3), triggering a caspase cascade that further cleaves a number of death substrates, including BID and cytoskeletal proteins, if glued, leading to apoptosis (Figure 2). Notably, inhibitors of apoptosis (IAPs) can inactivate caspases by specifically binding to their active sites. Caspase activator (SMAC)/Diablo and its functional homologs in flies, including Grim, Reaper, and Hid, can in turn target binding and degrade IAPs [17].
Schematic diagram of apoptotic signaling.
In addition, it should be noted that the interaction between TNF and TNFR1 may also activate other signaling pathways and allow cell survival rather than self-destruction.
In general, internal stimuli such as irreparable genetic damage, hypoxia (lack of oxygen), very high concentrations of cytosolic Ca2+, viral infection, or severe oxidative stress (i.e., production of large amounts of damaging free radicals) and cytotoxic drug treatment trigger apoptosis via the intrinsic pathway.
The intrinsic death pathway, i.e., the mitochondrial-received apoptotic pathway, is a death receptor non-dependent apoptotic pathway [18]. This pathway is activated by the release of cytochrome C (Cyto C) from mitochondria in response to various stresses and developmental death cues. The process specifically involves multiple steps as follows: apoptotic signals (various types of cellular stress), lead to the insertion of pro-apoptotic members of the Bcl-2 family of proteins (e.g., Bax), into the outer mitochondrial membrane, forming pores that mediate the release of Cyto C from the mitochondrial intermembrane space into the cell membrane. Once in the cell membrane, Cyto C molecules bind to Apaf-1 (a homolog of mammalian CED4) and further recruit procaspase-9 to form a complex of multiple subunits called the apoptosome. Then procaspase-9 is activated to become active caspase-9. Then the caspase-9 molecule cleaves and activates the downstream executor caspase (Caspase-3, 6,7) to carry out the apoptotic process (Figure 2) [19].
Bcl-2, the mammalian homolog of Ced-9, prevents apoptosis by inhibiting the release of CytoC from mitochondria [20]. IAPs, second mitochondrial activators of caspases (Smac), endonuclease G (Endo G), and AIF also have important roles in the apoptotic process [21]. Notably, Endo G and AIF are specifically activated by apoptotic stimuli and are able to induce ribosomal breakage of DNA independently of caspases. Endo G is a mitochondria-specific nuclease that translocates to the nucleus and cleaves chromatin DNA during apoptosis. AIF is a flavin adenine dinucleotide-containing, NADH-dependent oxidoreductase that resides in the mitochondrial intermembrane space, and its specific enzymatic activity remains unknown. In the presence of apoptosis, AIF undergoes proteolysis and translocates to the nucleus, where it triggers chromatin condensation and massive DNA degradation in a caspase-independent manner.
Previously, it was thought that the only apoptotic pathways were the mitochondrial pathway and the death receptor signaling pathway. Now, an increasing number of studies have shown that the endoplasmic reticulum (ER) also senses and transmits apoptotic signals [22, 23]. The sustained action of various apoptosis-inducing factors may induce a complex unfolded protein response (UPR) by interfering with the correct protein folding process. The UPR response causes endoplasmic reticulum stress, leading to cellular apoptosis due to the accumulation of intracellular misfolded proteins. ER, in addition to being the site of protein folding, it is also the main intracellular Ca2+ reservoir. Disturbing intracellular Ca2+ homeostasis can also induce the typical ER stress response. Interestingly, the localization of Bcl-2 family proteins (including Bcl-1, Bax, Bak,
It has been suggested that procaspase-12 is a proximal effector of apoptosis associated with the ER. Recent studies have found that although caspase-12 is processed and activated in ER stress-induced apoptosis in mouse cells, the enzyme is not absolutely necessary for this process. On the other hand, cells lacking caspase-8 or caspase-9 were highly resistant to ER stress-induced apoptosis. One of the mechanisms that could explain caspase-8 activation in the ER involves the recent discovery of an ER-resident potential apoptosis initiator, named neurotrophic receptor-like death domain protein (NRADD). This protein has a transmembrane and cytoplasmic region that is highly homologous to the death receptor. Induction of apoptosis by NRADD is dependent on caspase-8 activation but does not require the mitochondrial component of the death program.
In addition to propagating death-inducing stress signals, ER contributes to apoptosis initiated by cell surface death receptors and to pathways resulting from DNA damage. Modulation of ER calcium stores can sensitize mitochondria to direct pro-apoptotic stimuli and promote activation of cytoplasmic death pathways.
In short, the extrinsic (receptor-mediated), intrinsic (mitochondria-mediated), and endoplasmic reticulum stress-mediated apoptotic pathways ultimately converge by activating the same caspases, which cleave the same cellular targets. Apoptosis-inducing factors can be involved in diseases by activating apoptotic pathways that affect the rate of apoptosis, and may predominantly involve the first two pathways or all three of these pathways.
The mechanism by which apoptosis occurs is highly conserved in all animal cells. It is dependent on a family of proteins called caspases (c for cysteine and asp for aspartic acid). This family of proteins has many members and generally exists as inactive precursors (procaspases). Procaspases are generally activated by the catalytic cleavage of other (already active) caspases, forming an amplified network of protein cascades. The activation process of procaspases involves the formation of a heterodimer by cleavage and the combination of two dimers to form an active tetramer. During apoptosis, those responsible for initiation are known as initiator caspases; those responsible for cleavage of specific target proteins (e.g. nuclear lamina proteins, DNA degradation enzymes, cytoskeletal proteins, and cell–cell adhesion proteins) are the executor caspases.
Apoptotic mechanisms are present throughout the initial to final stages of animal development. Only the process requires a trigger to be activated for its occurrence. So, how is the first member of the caspase cascade reaction described above initiated? Initiator procaspases usually contain a caspase recruitment domain (CARD). This structural domain can assemble into an activation complex with an adaptor protein when the cell receives an apoptotic signal. The formation of this complex means that the promoter caspase will be activated by cleavage.
As mentioned above, there are numerous members of the caspases family, most of which are involved in apoptosis, but not all of them mediate apoptosis [24]. For example, the first discovered caspase, human interleukin-l-converting enzyme (ICE), was not associated with apoptosis but was responsible for mediating the inflammatory response. After the discovery of ICE, similar proteins to ICE were identified in
Peroxisomes, similar to the mitochondria, are a membranous subcellular organelle within eukaryotic cells. The peroxisome contains enzymes related to fatty acid and amino acid oxidation processes that produce hydrogen peroxide and also degrade hydrogen peroxide [25]. This gives the peroxisome its name and it plays an important role in maintaining intracellular oxidative metabolic homeostasis.
Because of the crucial role of the peroxisome, its dysfunction is associated with various pathological conditions, organ dysfunction, and aging [26, 27, 28]. For example, deficiency of Pex3, a peroxisomal membrane protein essential for membrane assembly, a member of the peroxisome (Pex) family, leads to complete loss of peroxisome function, while deficiency of Pex5, a peroxisome transporter, leads to Pex5 (a peroxisomal transporter) leads to the loss of peroxisomal matrix proteins. Mutations in this class of Pex genes may lead to human developmental abnormalities, such as human autosomal recessive disorders [29].
Peroxisomes play important roles in biosynthesis and signal transduction, which cannot be achieved without interaction with other organelles in the cell. In particular, peroxisomes interact functionally with mitochondria [30]. They cooperate with each other to perform biological functions such as production, fission, proliferation and degradation through vesicular transport, signaling, and membrane contact [31]. On the other hand, they can act synergistically to clear excess intracellular ROS, resist extracellular stresses through immune responses, and play an important role in the maintenance of lipid homeostasis through fatty acid β-oxidation [32, 33, 34]. In one word, peroxisomes are essential for the maintenance of normal mitochondrial and even whole cell function. Some chemotherapeutic drugs have been found to trigger mitochondrial dysfunction, leading to apoptosis by overwhelming cells with ROS. For example, Vorinostat (Vor), an FDA-approved histone deacetylase inhibitor (HDACi) for lymphoma treatment, has been well documented to trigger mitochondrial-mediated apoptosis through ROS accumulation. Acute Vor treatment has been shown to induce the expression of peroxisome proteins, thereby increasing peroxisome proliferation in a lymphoma model system. In addition, the knockdown of peroxisomes by gene silencing of Pex3 enhances Vor-induced ROS-mediated apoptosis [35].
In short, peroxisome dysfunction severely affects mitochondrial metabolism, cellular morphological stability, and biosynthesis, directly or indirectly contributing to a number of apoptosis-related diseases such as cancer [36, 37], cardiovascular disease [38, 39, 40], and neurodegenerative disorders [41].
Apoptosis is an important way for the organism to maintain the numerical homeostasis of the cell population. Excessive or insufficient apoptosis can lead to disease.
Crosstalk between mitochondria and other organelles is important in tumorigenesis. Mitochondria and peroxisomes are important organelles for ROS production and scavenging. Under normal conditions, both maintain intracellular ROS homeostasis. Impaired peroxisome function inevitably leads to increased levels of ROS in mitochondria, which impairs mitochondria, exacerbates impaired ROS clearance, leads to low levels of apoptosis, and thus promotes tumorigenesis and progression [42, 43, 44].
ROS act as signaling molecules to regulate various physiological and pathological processes [45]. H2O2 is a member of the ROS family and plays an important role in the signaling of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). H2O2 prevents protein tyrosine phosphatase 1B (PTP1B) from dephosphorylating EGF, thereby facilitating EGF stimulation. In addition, activation of PDGF requires H2O2 to promote oxidation and inactivation of PDGF-receptor-associated phosphatases and SHP-2, thereby facilitating the signaling pathway [46, 47]. Excessive ROS production can lead to cellular genomic instability (including mutations in the mitochondrial genome) on the one hand. Notably, ROS can promote tumor cell proliferation under hypoxic conditions. The reason for this is that the transcription factors hypoxia-inducible factors (HIFs) are upregulated under hypoxic conditions, thus promoting the expression of oncogenes. Although some proteases such as prolyl hydroxylases (PHDs) can degrade HIFs, the increased release of ROS induced by hypoxia can prevent the action of PHDs on HIFs. In this case, HIFs can then promote tumor progression under hypoxic conditions.
Briefly, because disruption of the functional balance between mitochondria and peroxidases may lead to increased ROS production, the increased ROS may inhibit apoptosis-inducing genes (bcl2 and p53, etc.), resulting in non-apoptosis of cells that should be apoptotic. Alternatively, the apoptotic process may be inhibited due to a decrease in the activity of apoptosis-related enzymes (caspases, etc.), leading to malignant cell transformation and tissue malignant proliferation. Both of these aspects are considered to be one of the important mechanisms leading to tumorigenesis and infiltrative metastasis.
Apoptosis is a form of death of terminally differentiated cardiomyocytes. Clinical data suggest that ROS generation, DNA damage, and other factors activate apoptosis, resulting in the loss of large numbers of cardiomyocytes in patients with advanced congestive heart failure, patients with myocardial infarction, and patients with diabetic cardiomyopathy. The evidence suggests that apoptosis may be an important pathogenetic mechanism in cardiovascular disease [38]. Apoptosis, in concert with necrosis, may also lead to foam cell death and thus to the formation of a necrotic core, which contributes to lesion instability and increases the risk of lesion rupture and thrombosis.
Lower levels of ROS production can lead to chronic remodeling of the heart, whereas high levels of ROS can directly lead to apoptosis in the cardiomyocytes [48]. It is therefore interesting that catalase overexpression inhibits cardiomyocyte apoptosis by protecting the cells from ROS [49]. Peroxisomal antioxidant enzymes and plasmalogens protect cardiomyocytes via the degradation and trapping of ROS and the maintenance of ROS homeostasis. Apoptosis of cardiac cells has been demonstrated in several cardiovascular diseases, including myocardial ischemia–reperfusion injury (I/R) and atherosclerosis [50, 51, 52]. Atherosclerosis, a major cause of heart failure and myocardial infarction, can likewise predispose to acute coronary heart disease. There is evidence that thrombosis and plaque rupture may be due to apoptosis of a large number of smooth muscle cells and macrophages in unstable atherosclerotic plaques [53, 54]. Rupture of atherosclerotic plaques with concomitant thrombus formation may lead to coronary artery occlusion, which affects the blood supply to the myocardium, resulting in myocardial infarction and leading to patient death. Reperfusion is an effective treatment for acute myocardial infarction, but it may cause reperfusion injury while restoring blood flow [55]. Studies in the last decade or so have shown that cardiac cell death occurring during reperfusion after myocardial infarction is mainly apoptosis, not cell necrosis, which breaks the long-held misconception [56, 57, 58]. Usually, what occurs during I/R is mostly cell apoptosis, whereas necrosis occurs more often after prolonged ischemia. In addition, apoptosis also plays an important role in myocardial remodeling after infarction. There is evidence that a large number of apoptotic cells can be detected in myocardium at the marginal zone of myocardial infarction [56]. Since the regenerative capacity of myocardium is limited, people show great interest in preventing apoptosis of myocardial cells during I/R.
There is also a connection between chronic heart failure and apoptosis [59]. It has been reported that patients with advanced heart failure have higher rates of cardiac myocyte apoptosis than normal subjects. Using transgenic mice with cardiac tissue-specific expression of caspase-8, it was found that apoptosis of cardiomyocytes, even at very low levels, can lead to fatal dilated cardiomyopathy as long as it occurs chronically [60]. In addition, the use of caspase inhibitors prevented left ventricular dilatation and improved ventricular function, suggesting that long-term apoptosis can lead to a significant reduction in cardiomyocyte numbers, which in turn gradually decreases cardiac contractile function. As a result, the remaining cardiomyocytes become overcompensated and contribute to cardiac hypertrophy, leading to the development of heart failure [61].
Regarding the major pathways involved in apoptotic signaling in the heart, the death receptor pathway, the mitochondrial, and ER-stress death pathways are all involved [62]. The cross-talk between death receptors and mitochondrial cell death pathways has been demonstrated in cardiomyocytes and the heart [63, 64]. For example, Date
In recent years, ER stress pathway has been reported to be in cross-talk with both the death receptor pathway and the mitochondrial pathway [13, 67, 68]. One study found that application of TNF-α induced HL-1 myoblast cell lines that activated both caspase-3 and -12 [69]. Bcl-2, which targets ER, inhibited mitochondrial membrane depolarization in apoptotic cells and also inhibited cytochrome c release [70]. Caspase-8 cleaves BAP31, an ER-associated protein, and the cleaved fragment induces Ca2+ release from ER, into the mitochondria, and initiates apoptosis [71]. It has also been reported that Bik proteins can activate Bax/Bak in the ER membrane after localization to the mitochondria, initiating Ca2+ release [72].
Regardless of the causative factor, and regardless of which signal transduction pathway or pathways are involved, oxidative stress due to the interaction of peroxisomes and mitochondria plays a pivotal role in triggering apoptosis and thus contributing to the development of cardiovascular disease.
Apoptosis plays a key role in the normal development of the central nervous system and is involved in the pathogenesis of adult brain-related diseases, such as stroke [73] and neurodegenerative diseases [74].
There is growing evidence that the decline in peroxisome function with age may be associated with age-related neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) [75]. In the brains of patients with Alzheimer’s disease and Parkinson’s disease, plasmin levels are significantly reduced [76, 77], which suggests peroxisome dysfunction in neurodegenerative diseases. The lack of peroxisome activity in aged cells accumulates cellular ROS, which can compromise the integrity of organelles including mitochondria and the peroxisome itself. Subsequent defects in energy production mediated by peroxisomal fatty acid metabolism and mitochondrial oxidative phosphorylation may lead to metabolic failure in aged postmitotic cells, thereby inducing apoptosis associated with neurodegeneration.
Huntington’s disease (HD), a prototypical neurodegenerative disorder, is caused by a mutation in the Huntingtin protein due to a repeat amplification of the CAG in the Huntington gene. Patients with this disease suffer from neuronal dysfunction due to massive apoptosis of nerve cells, which in turn manifests as mental cognitive and motor impairment, and even disability [74].
ROS can easily poison neurons due to their series of characteristics, such as rich in fatty acids, easy intracellular production of large amounts of hydroxyl radicals, weak antioxidant capacity, and low regenerative capacity. In addition, because of the high metabolic rates, neurons require a high energy supply from mitochondria, which are both the most important intracellular organelle for ROS production and also vulnerable to ROS attack. It has been shown that treatment of isolated cultured cerebellar granule neurons with hydrogen peroxide induces mitochondrial fission within 1 hour [78]. Furthermore, treatment of mice with nitric oxide in stroke leads to massive fission of neuronal mitochondria before the onset of neuronal loss [79]. In the presence of calcium, acute exposure to high levels of ROS can induce massive opening of mitochondrial membrane transition pores and increased permeability, which in turn causes cell Apoptosis or necrosis occurs. ROS production in mitochondria forms a vicious cycle with oxidative stress and is toxic to cells. There is some evidence in transgenic mouse models of HD that showed that Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid with antioxidant properties, prevents the production of reactive oxygen species, mitigates mitochondrial insufficiency and apoptosis, in part, by inhibiting Bax translocation from cytosol to the mitochondria [80]. TUDCA prevented striatal degeneration and ameliorated locomotor and cognitive deficits in a 3-NP (3-nitropropionic acid) rat model of HD. Keene
Apoptosis is a highly regulated cell death program that can be induced by a variety of physiological and pathological factors and has specific morphological and biochemical characteristics. The mechanism of its onset has not been completely elucidated to date, and it is now accepted that it is mediated by a number of pathways including the death receptor signaling pathway, the mitochondrial signaling pathway, and the endoplasmic reticulum signaling pathway. As an important way for the organism to maintain the numerical homeostasis of the cell population, apoptosis plays a key role in the pathogenesis of various human diseases. Peroxisomes and mitochondria are membrane-bound organelles in the cytoplasm of eukaryotic cells and are closely related to each other in their organelle synthesis and function. One of their important roles in cooperating with each other is to regulate the level and extent of apoptosis by maintaining the homeostasis of reactive oxygen species in the cell. Peroxisome dysfunction severely affects mitochondrial metabolism, cellular morphological stability, and biosynthesis, and therefore contributes directly or indirectly to a number of apoptosis-related diseases. Based on the available relevant findings, this chapter presents and summarizes the important potential role of peroxisomes in apoptosis-related diseases such as tumors, cardiovascular diseases, and neuropsychiatric disorders.
This work was supported in part by grants from National Natural Science Foundation of China (22176002), Anhui Provincial Natural Science Foundation (2008085 MB49), Natural Science Foundation of Anhui Provincial Department of Education (KJ2021A0215), Anhui Medical University Research Enhancement Program (2021xkjT004), and Open Project Fund of the Key Laboratory of the Ministry of Education for the Birth Population (JKZD20202).
The authors report no conflicts of interest.
IntechOpen publishes different types of publications
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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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Heshmati",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313921/images/system/313921.jpg",biography:"Dr. Hassan Massoud Heshmati is an endocrinologist with 46 years of experience in clinical research in academia (university-affiliated hospitals, Paris, France; Mayo Foundation, Rochester, MN, USA) and pharmaceutical companies (Sanofi, Malvern, PA, USA; Essentialis, Carlsbad, CA, USA; Gelesis, Boston, MA, USA). His research activity focuses on pituitary tumors, hyperthyroidism, thyroid cancers, osteoporosis, diabetes, and obesity. He has extensive knowledge in the development of anti-obesity products. Dr. Heshmati is the author of 299 abstracts, chapters, and articles related to endocrinology and metabolism. He is currently a consultant at Endocrinology Metabolism Consulting, LLC, Anthem, AZ, USA.",institutionString:"Endocrinology Metabolism Consulting, LLC",institution:null},{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/198499/images/system/198499.jpeg",biography:"Dr. Daniel Glossman-Mitnik is currently a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico, as well as a National Researcher of Level III at the Consejo Nacional de Ciencia y Tecnología, Mexico. 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. in Chemistry in July 2000, and his Ph.D. in Physical Chemistry in 2007 from the University of Khartoum, Sudan. In 2009 he joined the Dr. Ron Clarke research group at the School of Chemistry, Faculty of Science, University of Sydney, Australia 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. He then worked as Assistant Professor at the Department of Chemistry, University of Khartoum, and in 2014 was promoted to Associate Professor ranking. In 2011 he joined the staff of the Chemistry Department at Taif University, Saudi Arabia, where he is currently active as an Assistant Professor. His research interests include:\r\n(1) P-type ATPase Enzyme Kinetics and Mechanisms; (2) Kinetics and Mechanism of Redox Reactions; (3) Autocatalytic reactions; (4) Computational enzyme kinetics; (5) Allosteric acceleration of P-type ATPases by ATP; (6) Exploring of allosteric sites of ATPases and interaction of ATP with ATPases located in the 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. 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