\\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:"655",leadTitle:null,fullTitle:"Colorectal Cancer Biology - From Genes to Tumor",title:"Colorectal Cancer Biology",subtitle:"From Genes to Tumor",reviewType:"peer-reviewed",abstract:"Colorectal cancer is a common disease, affecting millions worldwide and represents a global health problem. Effective therapeutic solutions and control measures for the disease will come from the collective research efforts of clinicians and scientists worldwide. This book presents the current status of the strides being made to understand the fundamental scientific basis of colorectal cancer. It provides contributions from scientists, clinicians and investigators from 20 different countries. The four sections of this volume examine the evidence and data in relation to genes and various polymorphisms, tumor microenvironment and infections associated with colorectal cancer. An increasingly better appreciation of the complex inter-connected basic biology of colorectal cancer will translate into effective measures for management and treatment of the disease. Research scientists and investigators as well as clinicians searching for a good understanding of the disease will find this book useful.",isbn:null,printIsbn:"978-953-51-0062-1",pdfIsbn:"978-953-51-6821-8",doi:"10.5772/1163",price:139,priceEur:155,priceUsd:179,slug:"colorectal-cancer-biology-from-genes-to-tumor",numberOfPages:460,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"9395fca282ee086f4d33451bca1eadbc",bookSignature:"Rajunor Ettarh",publishedDate:"February 10th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/655.jpg",numberOfDownloads:47321,numberOfWosCitations:34,numberOfCrossrefCitations:21,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:55,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:110,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 16th 2011",dateEndSecondStepPublish:"March 16th 2011",dateEndThirdStepPublish:"July 21st 2011",dateEndFourthStepPublish:"August 20th 2011",dateEndFifthStepPublish:"December 18th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"78549",title:"Dr.",name:"Rajunor",middleName:null,surname:"Ettarh",slug:"rajunor-ettarh",fullName:"Rajunor Ettarh",profilePictureURL:"https://mts.intechopen.com/storage/users/78549/images/3518_n.jpg",biography:"Dr. Rajunor Ettarh is Professor and Vice-Chair for Education in the Department of Structural and Cellular Biology at Tulane University School of Medicine, where he also serves as Director of the Graduate Program in Anatomy. A Fellow of the Royal Society of Medicine in London, he spent much of his research career in Ireland, where his main interests centered on radiobiology and epithelial cell biology of the digestive tract, the regulatory mechanisms that mediate uninhibited proliferation in gastrointestinal cancers, and potential therapeutic targets. He has published extensively, has previously edited two books on colorectal cancer, and reviews for a number of cancer journals.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Tulane University",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1078",title:"Gastrointestinal Oncology",slug:"gastrointestinal-oncology"}],chapters:[{id:"28087",title:"Colorectal Cancer: It Starts and It Runs",doi:"10.5772/39167",slug:"colorectal-cancer-it-starts-and-it-runs",totalDownloads:1832,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Rajunor Ettarh",downloadPdfUrl:"/chapter/pdf-download/28087",previewPdfUrl:"/chapter/pdf-preview/28087",authors:[{id:"78549",title:"Dr.",name:"Rajunor",surname:"Ettarh",slug:"rajunor-ettarh",fullName:"Rajunor Ettarh"}],corrections:null},{id:"28088",title:"Germline Genetics in Colorectal Cancer Susceptibility and Prognosis",doi:"10.5772/27222",slug:"germline-genetics-in-colorectal-cancer-susceptibility-and-prognosis",totalDownloads:2121,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Amanda Ewart Toland",downloadPdfUrl:"/chapter/pdf-download/28088",previewPdfUrl:"/chapter/pdf-preview/28088",authors:[{id:"69289",title:"Dr.",name:"Amanda",surname:"Toland",slug:"amanda-toland",fullName:"Amanda Toland"}],corrections:null},{id:"28089",title:"The Role of Modifier Genes in Lynch Syndrome",doi:"10.5772/28021",slug:"the-role-of-modifier-genes-in-lynch-syndrome",totalDownloads:6127,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Rodney J. 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From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"60268",title:"Surgical Treatment of Burn Scars",doi:"10.5772/intechopen.72303",slug:"surgical-treatment-of-burn-scars",body:'\nToday, a lot of patients survive burn injuries, but they will not escape the burden of severe scar formation. The scarred tissue leaves contractures at joints, and this causes functional limitations. Surgical treatment is an indication to treat the burn scars [1]. In this chapter we explain the surgical treatment of burn scars.
\nSuperficial burn wounds usually heal without complications. Deep partial and full-thickness burns have an increased risk for hypertrophic scar formation [2]. In the burns that include epidermis, the dermis remains intact and re-epithelization occurs by keratinocytes. Superficial partial-thickness burns involve epidermis and superficial dermis which results in blisters. Superficial injuries may require careful monitoring only. In deep partial-thickness burns, prolonged time for re-epithelialization is needed [3]. Assessing the depth of burn earlier is important to administer optimal treatment and prevent hypertrophic scar formation. Wound healing has three phases: inflammation, proliferation and remodeling [4, 5]. The dorsal area of the hands is thin and susceptible to hypertrophic scar formation. Dorsal scarring of the hands may not only inhibit passive flexion at the metacarpophalangeal joint but in some severe cases further result in hyperextension and subluxation of the joint [6].
\nA healed burn patient may have varying degrees of scars with functional and aesthetic components. Depending on the depth of the burn injury, post-burn scars are inevitable even with the best treatment. Second-degree deep dermal and full-thickness burns heal by scarring. The post-burn scars may be immature/mature, atrophic/hypertrophic/keloid, stable/unstable, depigmented (vitiligo)/hyperpigmented. They can turn into malignancy as well [7]. Unfortunately, the head and neck area are the most frequently affected area involved in burn injuries [8]. Especially, the neck with its ability to develop severe contractures and its aesthetic importance, deserves more attention [9]. Achieving long-term results with patient satisfaction remains a challenge [10]. Pre-expansion of free and regional axial island flap have all contributed to achieve this goal [11, 12]. The color match of skin grafts might be poor and also not as elastic as face and neck skin [13, 14]. Pre-expansion of tissue is valuable when large areas need to be resurfaced. This helps to cover more surfaces enabling the closure of the donor site. Studies showed that pre-expansion increases vascularization, reliability and the amount of tissue needed to be transferred [15–17]. Pre-expansion also causes atrophy of all expanded tissue layers except the epidermis that makes the flaps become thinner [18]. If there is no scar formation and the donor site can be closed primarily, then local options should be preferred. Supraclavicular flaps are preferred to infraclavicular flaps because they have greater proximity as well as better skin and tissue match to the affected areas when compared with infraclavicular flaps. Pre-expanded groin flaps show thinner dermis, expand easily and can be harvested without patient repositioning. If locoregional options cannot be used, in comparison to scapular and parascapular flaps, pre-expanded groin flaps are preferred (Figure 1).
\nPost-burn treatment algorithm for head and neck contractures.
As a rule, surgical treatment for post-burn contractures should not be undertaken during healing and scarring which usually takes 1 year. The surgical management of any post-burn contracture involves complete release of contracture. To decrease the requirement for skin cover, incision can be performed. To have a relatively bloodless field, incision line can be infiltrated with 1:200.000 adrenaline solution. The limb contractures can be released under tourniquet which should be deflated after complete release and hemostasis is achieved. Generally, for the patients who have received pre-operative physical therapy and their scars have become soft, incision rather than excision is applied to release the contracture. For example, in a case of post-burn contracture of neck, the scars may extend from chin, neck onto the chest and even abdomen. In this case, partial excision of hypertrophic scars may sometimes be done. If there is a contracture, it should be completely released. In severe long-standing contractures, the musculotendinous units and neurovascular structures can be shortened. Hence, complete release might be impossible. For example, if the joints are subluxated or dislocated, complete release might be impossible. In this case, the possible release is done, and then, full correction is achieved by serial splintage, skin/skeletal traction or by using the modern distractor systems. After the full correction is performed, then the skin is covered over the area. After releasing the contracture, the defect must be covered by using skin grafts or a skin flap [7].
\nWhen we use the grafts sheet, grafts are preferred and expansion should not be preferred [13, 19, 20]. The junction line of the grafts’ sheets should be parallel to the joint motion axis. After immediately release, the skin grafts are applied. Generally, contractures are treated with split skin grafts of intermediate or thick variety. This helps the donor site to heal up spontaneously.
\nIf the contracture release is likely to open up the joint of the hands and feet or tendon nerve, surgery is planned at a later date, for example, for old healed electrical burns, the skin flap is a must. The surgeon must provide a flap cover after release of contracture. If the defect is located in a cosmetic area and the reconstruction with a flap is thought to give a better cosmetic result, then covering a flap should be considered. For example, to repair upper lip ectropion of a male patient, the flap can be provided from scalp or upper neck. If it is a female patient, a graft cover is needed to repair upper lip ectropion.
\nFor the split-skin grafts, thighs are usually used for harvesting. In a patient with severe burn and extensive scar formation, the grafts may be harvested from legs, abdomen and upper limb, scalp or back. In cases with multiple and massive contractures, the donor sites should be checked and plan charted out for “which donor site for which contracture.” For neck, axilla and facial resurfacing, large sheets are important to be required while comparatively smaller pieces of graft are adequate for eyelid or finger contractures [7].
\nThe grafts become stable usually in 3 weeks time. Daily physical therapeutic exercises are required to keep the joints in range of motion. These exercises are continued till the grafts mature and range of motion is achieved. Care of the grafted areas is done till the graft loses its tendency to contract and can be pinched and moved over the recipient area [7]. According to Burn Association Repositories’ data, it has been found that 500,000 burn victims seek medical treatment every year, and 39% of these injuries involve upper extremity and hand [2, 21, 22]. There are several risk factors for the formation of hypertrophic scars like young age, infection, skin stretch and anatomic location (axilla, neck) [23].
\nIn the acute phase of the thermal injury and during initial scar maturation, scar management can ameliorate hypertrophic scar formation and prevent scar banding. Timing of the operative procedure should allow enough time for complete scar maturation, as premature intervention can result in increased inflammation and additional scarring. Reconstructive procedures usually start 6 months after injury. For the correction of mild and moderate hypertrophic scar contractures, local skin flaps are commonly used to avoid more complex procedures [24]. Simple linear scar bands which can be seen across joints can be treated best with a scar-lengthening Z-plasty. The classic Z-plasty is designed with its central limb along the hypertrophic scar band and with a 60° angle of the lateral limbs. By making the corner 90° before extending the Z-plasty to 60°, perfusion to the tip of the Z-plasty is improved [25]. The flaps can be raised in scar tissue if maintained thick and involving underlying adipose tissue to achieve active lengthening of 75%. Creating the angle to 90° results in lengthening of 125%, however, involves larger limbs. To modify this approach, a series of smaller z-plasties along a scar can be performed. This helps to achieve similar lengthening but avoiding donor site morbidity with larger flaps. While larger flaps are used for axillary contractures, smaller flaps are used for palms and digits [26]. In web space contractures, modifications of plasties and a variety of local flaps are commonly devised [27, 28]. Because of its geometric design, the 5-flap Z-plasty is frequently used to create concavity and lengthening within the web space. Another option is the V-Y advancement flaps that use the supple dorsal tissue which is advanced into web space. These flaps can later on be combined with forms of z-plasties [29]. The second most common contractures behind neck contractures are the axillary scar contractures and they are difficult to improve. With z-plasties, small linear bands can be removed. Larger contractures can be treated with release and thick split thickness skin graft or full-thickness skin graft. Ogawa et al. describe treatment of severe contractures with pedicled flaps or with regional and free tissue transfer [30]. Usually palmar burn scars involve a large surface and result in tight contractures. Mild forms can be treated with a sequence of z-plasties. If it is a severe contracture, release of the scar may be required leaving a large defect. Full-thickness skin graft can be used to fill this defect. Full-thickness skin grafts are preferred over split-thickness graft because they have a decreased effect of secondary contraction to minimize scarring. If the contracture release leads to exposed tendon or bone, local flaps may be used [31].
\n\n
Proximal joint contractures should be released before distal contractures. For example, if the shoulder and elbow have limited range of movement, then there is a little value to have a mobile wrist.
If there are multiple joints requiring release, each joint should be considered separately and each contracture should be fully released. The Y-V plasty technique simultaneously leads to release of multiple joints.
Function is always prior over cosmesis; it is better to have a functioning joint with an albeit disappointing cosmesis than to have a cosmetically perfect joint without mobility. This does not mean cosmesis is not important but it should not take precedence over function.
When split-thickness graft is applied over a wound, it will again contract with the potential for recurrent contracture formation. To prevent this, physiotherapy is a method to mobilize the joint. A flap is much more preferred than a split-skin graft. It has its own blood supply and also supplies bulk, which might lead to better cosmetic appearance.
Sometimes, the important underlying structures may be exposed and require release. For example, a dorsal release of the ankle joint may leave extensor tendons exposed. In a long-standing contracture, ligaments and tendons may have permanently shortened, and tendon lengthening may be necessary for dorsiflexion.
Burn contracture release is undertaken once it is deemed “mature.” Interfering with an active scar leads further contracture formation. Contracture and hypertrophic scar formation increases in the first 6 months, and full scar maturation will occur after 2 years. When the scar is active, it is pliable and amenable to stretching by physiotherapy [32].
\nTo reconstruct the contracture, surgical treatment should be combined with release and split-skin grafting. This recently is called conventional waiting approach. For example, in the acute lower lid treatment, some studies showed that full-thickness grafts reduce the incidence of subsequent ectropion release [33]. It is important that, when flap cover of the defect is planned, this timing restriction is not applicable. Some authors support waiting for 2 or 3 weeks acutely, prior to undertaking release and free flap cover, and have reported success rates of 94% [34].
\n\n
Split-skin grafting
Local plastic surgical procedures
Z-plasty
Y-V plasty
Full-thickness skin grafting
Flap cover
Artificial skin substitutes
Tissue expansion with or without flap cover
When there is a mild contracture which means that there is 50% of joint movement possibility, to lengthen the scar, Z-plasty can be performed. In more severe cases, different surgical procedures are needed.
\nTo remove the contracture, even a band or a sheet of scar tissue must be fully released. Unless local adjacent skin flaps are used, the release and the reconstruction can be considered as two different procedures, e.g., Z-plasty. The contracture release incision must be placed at the meridian of the joint and must be “fish-mouthed” at either end, and should extend into normal tissue medially and laterally. Using a swab on the index finger will “sweep” tissue away from the center contracture and divide “softer” bands. By using this manoeuvre, the extent of the defect to be covered will be increased. It is also designed to be sure that the wound is formed from normal tissue, not scar.
\nThis traditional method of split-skin grafting helps the defect import non-scarred, healthy, non-bulky skin without the need to compromise local tissues. The graft is ideally harvested from buttocks or scalp, which are cosmetically acceptable sites [35]. Once the contracture is fully released and full joint extension is achieved, then the graft is only applied to the wound bed. The ability to release multiple joints at the same sitting is an advantage, but leading to hypertrophic scar formation is a disadvantage. Also, when a split-skin graft is placed on a wound bed, the wound will again contract and recurrence might occur and re-release can be required again.
\nBecause there is a risk such as immobilization difficulty, bleeding and infection, the split-skin grafts are at risk of suboptimal “take.” Then the patient needs physiotherapy for motion of joint especially in children. Donor site morbidity is also a problem.
\nIf there is a contracture which is due to a band, then a “local” procedure which both divides the contracting band and lengthens it is amenable avoiding the need for a donor site. The Z-plasty is a technique that divides the scar contracture and lengthens the band by importing local lateral adjacent tissue. Z-plasty does not create new tissue to lengthen the band, but borrows tissue adjacent to the contracture. Unless there is a short contracture band with a good deal of lax adjacent skin, Z-plasty is possible. These can be thought of as Z-plasty-in-parallel or Z-plasty-in-series [36]. The Z-plasty-in-series (e.g., five-flap Z-plasty) recruits a large amount of adjacent tissue. The Z should always be designed as large as possible. The bigger the Z-plasty is in size, the greater the lengthening obtained. When compared the Z-plasty-in-parallel (e.g., multiple single Z-plasties) recruits much less adjacent tissue than Z-plasty-in-series. The actual lengthening obtained is relatively less (Figure 2).
\nZ-plasty in series (5-flap Z-plasty); Z-plasty in parallel (multiple Z-plasties).
If the surrounding tissue is less pliable, this technique can be used. There is a risk of ischemic necrosis when the undermining and subsequent transposition of skin flaps are in an area of scarring and fibrosis (especially the tips). The reorientation of the scar can also result in distortion of the surrounding tissues.
\nY-V plasty is especially useful in linear sheet contractures. The V extends the whole length of the band, and the Y passes into normal skin. The scar is not excised. The flaps simply are pulled forward to form a V [37]. To achieve this, skin laxity should be enough [38], and the “pinch” test is useful to evaluate this [39].
\nThe advantages of this technique:
There is little risk of flap tip necrosis because the blood supply of the flaps is less compromised as there is no need for undermining.
This technique effects reorientation of scar tissue.
The contracture band length is not important. This technique is especially useful in very long contracture bands. The running Y-V plasty is especially useful in these cases.
100% lengthening of the long axis of the contracture which is the theoretical lengthening of the contracture [38].
This is only true when the flap can be advanced half the length of the sides of the V forming the flap. For two reasons, the actual lengthening obtained is much less than it is supposed to be. The first reason is as the burnt tissue has lost its elasticity, it is often difficult to advance the burnt skin. The second reason is interdigitation of each adjacent advancement flap. While using the “straight-line” advancement flaps, the problem is that the stretching of the skin limits the actual obtained lengthening. That is the reason only Y-V technique can be applied in mild contractures.
Y-V plasty is a simple procedure. While the operation is performed, the flap advancement degree can be refined. There is a disadvantage of this technique. Excision of a thick scar band is not actually possible, and there are poor cosmetic results (Figure 3).
Y-V plasty. V is marked along the contracture band and Y extension passes into normal tissue on each side.
The W-plasty, double-reverse V-Y plasty [40] and X-plasty [41] are the variations of the methods described above. To remove web-shaped burns, the seven-flap plasty has been described [42].
\nAfter the contracture release is complete, reconstruction with full-thickness grafting has a better texture match than with split-skin grafting, and is associated with less recurrence [13]. A full-thickness graft provides less wound contraction, because it has more dermis in the graft. After large burns, there may be limited available skin; thus in such cases, full-thickness grafts are impractical. Taking graft is much more tenuous than with split-skin grafts, when a contour to the underlying bed is required, like whole cheek, which is not a flat surface. Full-thickness grafts need a healthy bed on which to take and leave a donor site. They usually exhibit hyperpigmentation which causes poor cosmetic results.
\nFlap cover can be either a pedicled flap or free flap. To release the burn contracture, both local [43] and free [44] fasciocutaneous flaps are successfully used. In most of the superficial burns, perforators to the deep fascia are usually protected. In this case, a burn scar may itself be used as part of this flap [43]. In large burn areas, local pedicled flaps are sometimes inappropriate, however, due to the lack of local skin plasticity or simply a paucity of available or acceptable donor sites. In this situation, using a free flap should be considered. The latissimus dorsi, serratus anterior, lateral arm, scapular, gracilis, anterolateral thigh, arterialised venous and temporalis fascial flaps are generally used [34]. There is a wide variety of flap choice which allows the surgeon to make judgments according to each individual case. There is no risk for recurrence, and this is the key advantage of flap. Free flaps may lead to an unacceptable cosmetic result because they import tissue different in color, thickness and texture. The flaps size must be as the same size as the defects size. Free flaps lead to a large donor defect and often require themselves a covering split-skin graft. Usually the adjacent tissue is burnt and the thick hypertrophic nature of the scar may make dissection of the recipient vessel difficult. Microvascular circulation should be kept up at higher level. Post-operative complications including complete or partial failure are disastrous. The free flap is an expensive and demanding procedure. It is a good option to apply when only one joint has a severe contracture from broad sheet of scar in the extremities.
\nFollowing Yannas and Burke’s original design, artificial skin templates have been developed [45]. Integra is a bilayer artificial dermis product consisting of porous bovine collagen spongy matrix combined with an overlying temporary epidermal substitute comprised of a silicone sheet. Combination of bilayer artificial dermis with split-skin grafting has been used by Soejima to reconstruct burn contractures [35]. The skin quality resembles full-thickness skin and also there is improved flexibility and suppleness, and scar hypertrophy does not exist [46]. There is reduced inflammatory response accompanying artificial skin substitutes, thus leading to reduced contraction. Donor site morbidity from split skin graft harvesting lower take rates than conventional autografts, more intensive dressing requirements and higher cost implications are the disadvantages [47]. This procedure has two steps. Sometimes it is noticed that areas of keloid scarring (and joint extremities in children) do not give good response to artificial dermis and tend to lead to recontracture or hypertrophic scar formation [35]. Hunt et al. treated a small series of neck contractures with Integra and they all developed recontracture [48]. The results of Integra over joints are disappointing despite adequate splintage [46]. In the management of complex wounds, Integra has been successful, but contamination and subsequent infection can lead to adverse results. A multicenter post-approval study in the United States including 216 burn injury patients found that the total incidence of infection in Integra-treated sites was 16.3% [49]. Another multicenter study managed with Integra following release of scar contractures noted a 20% infection rate. The second most common complication underneath Integra was fluid collection with 14% [50]. Matriderm is a thin (1 mm) single layer dermal matrix composed of collagen types I, III, and V and it has been marketed as a single-stage dermal template for reconstruction [51].
\nExpansion of tissue is a simple procedure. The color, texture and thickness of the expanded skin is the same as adjacent skin. Tissue expanders together with a pre-expanded free [52] or fasciocutaneous flap [53] can be used in contractures caused by burns. Expansion of tissues helps the maximum utilization of the non-involved areas.
\nThe number of new scars and donor site morbidity is reduced. Neck, chest and scalp are the most suitable areas where tissue expansion is commonly performed. In the lower limb, expansion is especially difficult in the burned extremity [54]. While planning the expansion, it is often difficult to predict the size of the defect. Expansion has the risks of infection, leakage and skin ischemia, and even failure. The patients should attend regular follow-up to improve outcomes and reduce complication rates.
\n\n
Is the reason for the contracture an intrinsic force or an extrinsic force?
For example, if there is a burn scar on the cheek, then lower lid ectropion can occur without any intrinsic lower eyelid deformity.
How is the severity of the contracture? Is the joints range of motion more than 50%?
Is the cause of the contracture a broad sheet of scar or a band of scar?
What is the cause of the contracture? If it is a band, then is it surrounded by normal tissue or a burned tissue?
Check if the band includes only one joint or if it involves other joints.
Below, there is an algorithm to help surgeons to choose the best reconstruction process for burn contractures after release (Figures 4 and 5) [32].
\nAlgorithm for the cover of burn contractures of the extremities after release: band contracture (ROM = range of motion).
Algorithm for the cover of burn contractures of the extremities after release: broad sheet of scar (ROM = range of motion).
The algorithms above are an attempt to simplify the approach to burn contracture release. Naturally, there are situations where the algorithm might not be applicable, and the surgeon, in all such cases, must plan an approach according to knowledge and experience.
\nUrea cycle is one of the most important pathways in the human body. The continuous degradation and synthesis of cellular proteins occur in all forms of life. High rates of protein degradation occur in tissue undergoing structural rearrangements.
Approximately 75% of liberated amino acids are reutilized. Since the excess amino acids are not stored, those not immediately incorporated into new proteins are degraded rapidly. The excess nitrogen from amino acids forms urea. As a hydrosoluble compound, urea is excreted by the kidney. Uremia is a clinical syndrome marked by elevated concentrations of urea in the blood and is associated with many metabolic disorders such as acidosis, abnormalities in lipids, mineral and homocysteine metabolism, oxidative stress, chronic inflammation, insulin and erythropoietin resistance, vitamin D deficiency, and malnutrition. Uremia more commonly develops with chronic kidney disease (CKD), but it also may occur with acute kidney injury if loss of renal function is rapid. Nearly all body organs and systems are affected by the toxicity of uremic compounds retained in the course of renal dysfunction. According to the European Uremic Toxin Work Group, uremic toxins are defined as accumulated solutes, normally excreted by the kidneys, that interact negatively with biological functions [1]. This has shown the need for the search for new uremic compounds, combining them into panels of substances involved in the pathophysiological processes. As example we can mention uridine adenosine, a strong vasoconstrictor, which is considered as a new uremic toxin. It has been demonstrated that uremic patients have increased levels of uridine adenosine, which can influence blood pressure, proliferation rate of vascular smooth muscle cells, and vascular calcification [2]. All these effects correlated with vascular dysfunctions and development of atherosclerosis. As uremic toxins are considered some components, which concentrations are not directly associated with glomerular filtration, but interacts negatively with vascular physiology. Several acute-phase proteins, IL-1, IL-6, IL-12, α2-macroglobulin, fibrinogen, and myeloperoxidase, together with endothelium-related proteins, such as vascular cell adhesion molecule 1, vascular endothelial growth factor 1, and soluble vascular endothelial growth factor receptor, increased in CKD and play a crucial role in endothelium dysfunction promoting the development of atherosclerosis. Renal failure is associated with an increased risk of cardiovascular disease [3, 4]. One of the main mechanisms underlying this increased cardiovascular risk is dyslipidemia [2]. In uremic environment lipids are affected by oxidative stress. The end products of lipid peroxidation process affect the circulating lipoproteins, lipidic and proteinic, leading to profound alterations of their biological properties, changing their interactions with biological functions and especially cardiovascular physiology. For this reason, lipoproteins, in renal failure, can be also considered as uremic toxins.
In the human body, dietary lipids absorbed from intestine and lipids synthesized by the liver and adipose tissue must be transported between the various tissues and organs for utilization and storage. Since lipids are insoluble in water, the problem on how to transport them in aqueous blood plasma is solved by associating nonpolar lipids (triacylglycerol and cholesterol esters) with amphipathic lipids (phospholipids and cholesterol) and proteins, to form water-soluble particle known as lipoproteins.
The plasma lipoproteins are classified as chylomicrons and very-low-density (VLDL), intermediate-density (IDL), low-density (LDL), and high-density (HDL) lipoproteins, according to their ultracentrifugation characteristics. Chylomicrons and VLDL serve as vehicles to transport triglycerides to the sites of consumption, as myocytes and suprarenal glands or storage in adipocytes. HDL fraction serves as a vehicle to transport surplus cholesterol from peripheral tissues to the liver for disposal. Many enzymes, enzyme activators, and protein parts, such as apolipoproteins and specific hepatic and extrahepatic receptors, are involved in lipoprotein metabolism.
Apolipoproteins (Apo), the protein part of lipoproteins, are present in each lipoprotein and carry out several roles. They can be part of the structure of lipoproteins, serve as an enzyme cofactors or inhibitors, and finally act as ligands for interaction with lipoprotein receptor in tissue. Apolipoproteins of HDL are designated as A (A-I, A-II, A-IV). Apo A-I is an activator of enzyme lecithin-cholesterol acyltransferase (LCAT) and serves as a ligand for HDL binding to specific scavenger receptor B1 (SR-B1). Apo A-II is an inhibitor of enzyme lipoprotein lipase. The main apolipoprotein of LDL and VLDL is Apo B-100, while the chylomicrons contain Apo B-48. Apo B-100 acts as ligand of LDL for LDL receptors in the liver and extrahepatic tissue. Apo B-48 is part of the structure of chylomicrons. Apo E is found in chylomicrons, VLDL, and HDL, and its role is to uptake the remnant of chylomicrons by a receptor specific for apolipoprotein E, in the liver. Apo C-I, Apo C-II, and Apo C-III are transferable between several different lipoproteins. Apo C-II is activator, whereas Apo C-III is an inhibitor for enzyme lipoprotein lipase. The Apo C-I is an inhibitor for enzyme cholesteryl ester transfer protein (CETP).
The main enzymes involved in lipoprotein metabolism are lipoprotein lipase (EC 3.1.1.34), hepatic lipase (EC 3.1.1.3), lecithin-cholesterol acyltransferase (EC 2.3.1.43), and acyl-CoA cholesterol acyltransferase (ACAT) (EC 2.3.1.26).
Lipoprotein lipase is located on the walls of blood capillaries of the heart, adipose tissue, spleen, lung, renal medulla, aorta, lactating mammary gland, and diaphragm. It is abundantly produced as an inactive enzyme by myocytes, adipocytes, and several other cell types. The inactive enzyme requires sequential glycation and cleavage of a 27-amino acid peptide to become functionally active. The role of lipoprotein lipase is the hydrolysis of triglyceride-rich lipoproteins, as chylomicrons and VLDL. Apo C-II and phospholipids are cofactors for enzyme activity, while Apo A-II and Apo C-III act as inhibitors.
Hepatic lipase is bound to the surface of hepatic cells. Hepatic lipase catalyzes hydrolysis and removal of the triglyceride content of HDL and chylomicron remnant. Accordingly, hepatic lipase plays a central role in the metabolism of chylomicron remnants and HDL.
LCAT is the enzyme of HDL, which is activated by Apo A-I, the structural protein of HDL. The enzyme plays an important role in HDL-mediated cholesterol uptake from the extrahepatic tissues and, as such, serves as a main determinant of HDL maturation and plasma HDL cholesterol level.
The formation of cholesteryl esters from cholesterol and long-chain fatty-acyl-coenzyme A catalyzes the enzyme called ACAT. It is a membrane-bound protein and, at the single-cell level, serves as a regulator of intracellular cholesterol homeostasis. In addition, ACAT supplies cholesteryl esters for lipoprotein assembly in the liver and small intestine.
Cholesteryl ester transfer protein is a hydrophobic glycoprotein that is secreted mainly from the liver and circulates in the plasma, bounded mainly to HDL [5]. It mediates cholesterol ester transfer from HDL to IDL in exchange for triglycerides. CETP promotes the transfer of cholesteryl esters from anti-atherogenic HDLs to pro-atherogenic Apo B-containing lipoproteins, including VLDL, VLDL remnants, IDL, and LDL. In this way CETP transfers lipids from one lipoprotein particle to another in a process that results in equilibration of lipids between lipoprotein fractions.
The exogenous pathway of lipid metabolism begins with chylomicrons. Chylomicrons are responsible for the transport of all dietary lipids into the circulation. They are produced within the enterocytes containing triglycerides, cholesterol ester, and phospholipids. Apo B-48 is essential for chylomicron formation. The nascent chylomicrons, from the small intestine, are released into the circulation via the lymphatic system. In the circulation, the nascent chylomicrons acquire Apo E and Apo C-II, which are in the surface of HDL. Apo C-II is an activator for enzyme lipoprotein lipase. The endothelium binding accommodates interaction of chylomicrons with the endothelium-bound lipoprotein lipase. Reaction with lipoprotein lipase results in the loss of approximately 90% of triglycerides in chylomicrons. The majority of fatty acids released diffuse into the adjacent myocytes for energy production or into adipocytes for energy storage. After hydrolysis chylomicron remnants are subsequently cleared by the liver and other tissues. Uptake is mediated by a receptor specific for Apo E. Both the LDL (Apo B-100 and Apo E) receptor and LDL receptor-related protein (LRP), specific for Apo E, are believed to take part. Chylomicron remnants return the borrowed Apo C- II and Apo E to HDL before their uptake by the liver and other tissues (Figure 1).
Chylomicron metabolism. Chylomicrons, from the small intestine, are released into the circulation by apolipoprotein B-48 (B48). Nascent chylomicrons acquire apolipoprotein (Apo) E (green square) and C-II (purple circle), which are in the surface of HDL. Apo A-I (white triangle marked with a) is a main apolipoprotein of HDL. Apo E and Apo C-II are necessary for activation of lipoprotein lipase and for uptakes of remnant chylomicrons by an LDL receptor and LDL receptor-related protein. TG-triglycerides, C-cholesterol, P-phospholipids.
VLDL particles are produced by the liver and are precursor of IDL and LDL. VLDL serves as the vehicle for delivery of endogenous lipids, endogenous triglycerol, and cholesterol, to the peripheral tissues. Nascent VLDL is formed within the hepatocyte and Apo B-100. Those are triglyceride-rich lipid droplet, followed by the addition of Apo E, Apo A-I, and Apo A-II. The triglycerides and cholesterol ester used by hepatocytes for incorporation into VLDL are generated by the enzymes acyl-CoA diacylglycerol acyltransferase (DGAT; EC 2.3.1.20) and ACAT. Apo C-II and Apo E, borrowed from HDL, are important for subsequent metabolism of VLDL by lipoprotein lipase and the VLDL receptor. Enzyme lipoprotein lipase is activated by the apolipoprotein C-II, and this is followed from the hydrolysis of VLDL triglycerides by the activated enzyme, leading to release fatty acids, which diffuse into the adjacent myocytes or adipocytes for energy production or storage. Lipolysis of VLDL results in reduction in their triglyceride content and detachment and release of a remnant particle, known as IDL. IDL particles may undergo further lipolysis via hepatic triglyceride lipase. Apo E serves as a ligand for remnant VLDL or IDL binding to specific receptors in the liver. This leads to the extraction of nearly all remaining triglycerides from IDL by the liver and formation of cholesterol-rich LDL. LDL particles are then removed via LDL (Apo B-100) receptor by the liver, as well as extrahepatic tissue (Figure 2).
Very-low-density lipoprotein metabolism. In circulation VLDL are transformed into intermediate-density lipoprotein after lipoprotein lipase activation by apolipoprotein C-II. IDL are removed by hepatic LDL receptors specific for apolipoprotein B and E. Apo E and Apo C-II are borrowed from high-density lipoprotein. A, Apolipoprotein a; B-100, Apolipoprotein B-100; C, Apolipoprotein C; E, Apolipoprotein E; LDL, low-density lipoproteins; TG, triglycerides; C, cholesterol; P, phospholipids.
HDL is synthesized and secreted from the liver and intestine. A major function of HDL is to act as a repository for the Apo C-II and Apo E, for metabolism of triglyceride-rich lipoproteins, chylomicrons, and VLDL. Also, the primary function of HDL is retrieval and transport of cholesterol from the tissue to the liver which is known as reverse cholesterol transport. This cycle is very important for cellular cholesterol homeostasis. The principal apolipoprotein constituents of HDL are Apo A-I and Apo A-II. As the main structural constituent of HDL, Apo A-I is the activator of enzyme LCAT. LCAT system is involved in HDL-mediated removal of excess unesterified cholesterol from triglyceride-rich lipoproteins and tissues. Apo A-II serves as an activator of hepatic lipase, which plays a central role in the removal of HDL triglycerides by the liver. HDL-mediated removal of surplus cholesterol from extrahepatic tissues requires attachment of nascent HDL to the ATP-binding cassette transporter type I (ABCA1). Binding to ABCA1 appears to trigger active transfer of phospholipids to nascent HDL, a step which is necessary for efficient translocation of free cholesterol from adjacent caveolae to the surface of HDL. Free cholesterol reaching the surface of HDL moves to the core of HDL. In this process nascent discoidal HDL is transformed into spherical HDL 3. After being accepted by HDL3, the free cholesterol is then esterified by LCAT to cholesterol esters, increasing the size of the particles to form the less dense HDL2. In the next step, HDL2, released in circulation, participates in a series of elaborate exchanges of apoproteins and lipids with the Apo B-containing lipoproteins such as chylomicrons, VLDL, and IDL, before reaching the liver. Actually, HDL in circulation receives triglycerides from Apo B-containing lipoproteins in exchange for cholesterol esters, a process catalyzed by CETP. Finally, HDL-2, via Apo A-I, binds to the scavenger receptor B1, which has been identified as a HDL receptor in the liver. The cycle is completed by the reformation of HDL 3, either after selective delivery of cholesteryl esters to the liver via SR-B1 or by hydrolysis of HDL2 phospholipids and triglycerides by hepatic lipase. Released, free Apo A-I forms preβ-HDL with the minimum amount of phospholipid and cholesterol. Preβ-HDL is considered the most potent form of HDL in inducing cholesterol efflux from the tissues to form discoidal HDL (Figure 3).
High-density lipoprotein metabolism. As the main structural constituent of HDL, apolipoprotein A-I (Apo A-I), is the activator of enzyme lecithin-cholesterol acyltransferase. LCAT system is involved in HDL-mediated removal of excess unesterified cholesterol from tissues and its esterification. Scavenger receptor B1,and ATP-binding cassette transporter type I.
CKD is associated with increased oxidative stress, which promotes covalent modifications of lipids and lipoproteins. Oxidative stress is an imbalance in the reactive oxygen species (ROS) production and their degradation ratio. ROS include various compounds such as superoxide anions, hydroperoxide, and hydroxyl radical. These compounds are produced under physiologic conditions, during energy production in mitochondria by reducing oxygen during aerobic respiration.
But excessive ROS levels may have a harmful effect on tissue function and structure, because of their interaction with different biomolecules in the human body, such as nucleic acids, proteins, and lipids. This interaction results with oxidative modifications of these biomolecules.
Under physiologic conditions, the production of ROS is balanced by antioxidant mechanisms that protect the cells from oxidative damages. The antioxidant mechanisms include enzymes; superoxide dismutase (SOD, EC 1.15.1.1) which catalyzes the dismutation of O2•− into H2O2; and glutathione peroxidase (GPX, EC 1.11.1.9), which detoxifies H2O2 and other hydroperoxides. Reduced glutathione (GSH), as a non-enzymatic antioxidant, allows the scavenging of OH. The redox reactions are catalyzed by glutathione peroxidase. In antioxidant mechanisms also included several compounds such as HDL, albumin, tocopherols, ferritin, ceruloplasmin, transferrin, ubiquinol, flavonoids, and carotenoids.
HDL is well known for its protective antioxidant properties. Protein paraoxonase-1 (PON1, EC 3.1.8.1), bound to HDL, exhibited antioxidant effects, against lipid peroxidation. Selenium Glutathione-peroxidase 3, also known as glutathione peroxidase 3 (GPX3, EC 1.11.1.9), is another antioxidant enzyme, which is associated with HDL. Besides many functions in the human body, albumins are known for the antioxidant function too. In the first place concerning the lipid peroxidation, albumin can scavenge hypochlorous acid, responsible for chlorination of proteins mediated by myeloperoxidase, and through its reduced cysteine residue can scavenge hydroxyl radicals. One of the physiological functions of albumins is the transportation of insoluble components, through the blood plasma. In this way, albumins bind the long-chain fatty acids (LCFA), polyunsaturated fatty acids (PUFAs), and cholesterol and in the circulation, preventing them from oxidative modifications. Albumins bind also the ligands such as copper, iron, α-tocopherol, bilirubin, and homocysteine and prevent their antioxidant damages. Tocopherol is an important antioxidant in the human body, because of its ability to intercept intermediary radicals during the lipid peroxidation process. Most antioxidant mechanisms described above are decreased in patients with renal failure, leading to a higher sensitivity to oxidative stress. These patients have low activity and concentration of Glutathione, low concentration of HDL, PON-1 and GPX3 enzymes, albumins and antioxidant vitamins such as vitamin E, D and C. This decreased antioxidant status, enhanced oxidative stress, and affected lipids and proteins leading to lipoproteins modifications and dysfunction. Lipids are one of the compounds mostly attached to oxidative stress. The peroxidation of lipids began with the reaction between a free radical with a polyunsaturated fatty acid containing more than two double bounds and formation of a lipid radical. In the next reaction, lipid radical can create lipid peroxyl radicals (LOO•) in reaction with oxygen, which can further react with other lipids forming new lipid radicals and lipid hydroperoxide (LOOH). Malondialdehyde (MDA) and 4-OH-2,3 alkenals are the end products of lipid hydroperoxide degradation. MDA covalently binds to proteins and nucleic acids, interfering with their normal biological functions. Binding to nucleic acids, MDA induce mutations and base-pair substitutions [6].
Binding to lysine amino group of protein part of lipoproteins, MDA created toxic adducts known as advanced lipoxidation end products (ALEs). In general, ALEs exhibit several pro-inflammatory effects and are involved in atherosclerosis [7]. These ALEs on Apo B result with oxidative modification of [8]. 4-OH-2,3 alkenals can also react with proteins, exactly with histidine, cysteine, and lysine residues and, create ALEs [9], which generate modified LDL. In this modified form, LDL can activate macrophages and increase the upregulation of class A scavenger receptors involved in the transformation of LDL into foam cells [10]. Another end product of lipid peroxidation is F2α-isoprostanes. Oxidation of arachidonic acid by a cyclooxygenase-independent pathway generates F2α-isoprostanes, known for atherogenic properties, because of their implication on platelet aggregation via Thromboxane A2 receptor, vasoconstrictive effects on smooth muscle cells, and endothelial cell proliferation and endothelin-1 secretion [11]. These three end products are routinely used for in vivo evaluation of lipid peroxidation level [12].
Renal failure is characterized by specific metabolic abnormalities of plasma lipoproteins [13]. These abnormalities involve all lipoprotein classes and show variations depending on the degree of renal impairment. Uremic lipid profile includes increased VLDL, IDL, small dense LDL particles, lipoprotein (a), and decreased HDL. Besides the changes in their concentration and structure, as stated above, uremic environment can strongly modified circulating lipoproteins leading to profound alterations of their biological properties and toxic effects in different cells and tissues. This has led to the formulation of an accelerated atherogenesis hypothesis and has been commonly linked with the lipid metabolic alteration associated with uremia.
Hypertriglyceridemia is common a disorder in uremic patients. Several studies have shown increased concentration of triglycerides even though serum creatinine levels are within normal range [14]. The predominant mechanism responsible for increased concentration of triglyceride-rich lipoproteins, including chylomicrons, VLDL, and their remains, is delayed catabolism and increased synthesis Apo B-48, the essential for chylomicrons metabolism. There are evidences that Apo B-48 levels are increased and inversely correlated with glomerular filtration and proteinuria [15]. In circulation, triglyceride-rich lipoproteins acquire Apo E and Apo C-II, which are in the surface of HDL. In uremic patients, concentrations of Apo E and Apo C-II, which are necessary for activation of lipoprotein lipase and for uptakes of remnant chylomicrons and VLDL by a receptor specific for Apo E, are reduced. Such defect leads to a reduced release of triglycerides in peripheral tissues and to an accumulation of triglycerides. Delayed catabolism of triglyceride-rich lipoproteins occurs probably because of a decreased activity of hepatic triglyceride lipase and lipoprotein lipase. Moreover, significant evidence showed that enzyme lipoprotein lipase is lacking in renal failure [16]. There are evidences that diminished activity of enzyme is a consequence of the downregulation of the enzyme gene [17]. There is also downregulation of hepatic lipase expression [18].
The presence of lipoprotein lipase inhibitors also contributes to delayed triglyceride-rich lipoprotein catabolism. Apolipoprotein C-II is an activator, whereas apolipoprotein C-III is a direct lipoprotein lipase inhibitor. A decrease in apolipoprotein C-II/ apolipoprotein C-III ratio due to a disproportionate increase in plasma apolipoprotein C-III may be the cause of lipoprotein lipase inactivation, which further contributes to hypertriglyceridemia [19].
As it is mentioned above, triglyceride-rich lipoproteins, chylomicrons, and VLDL,need apolipoprotein C-II and apolipoprotein E for their maturation, which are delivered by HDL-2. In uremic patients HDL metabolism is impaired and HDL-3 are not maturated into HDL-2 due to a LCAT deficiency [20].
In healthy persons, VLDL and chylomicrons are transformed into IDL and chylomicron remnants after lipolysis in peripheral tissue. Chylomicron remnants are removed by the specific receptors of the liver, via LDL (Apo B-100 and Apo E) receptor and LDL receptor-related protein. It has been demonstrated that LDL receptor protein is downregulated in uremic patients [21] which leads to increasing levels of exogenous triglycerides. In physiological conditions, surplus IDL is transformed into LDL by the removal of their triglycerides by the hepatic lipase and enrichment in cholesteryl esters from HDL-2 by CETP. But the lack of HDL-2 impedes this process and leads to the accumulation of pro-atherogenic IDL [22]. There is a downregulation of hepatic lipase expression [18]; thus hepatic lipase deficiency which decreased conversion of IDL to LDL and lack of HDL work in concert to rise plasma concentration of IDL. A part of VLDL is removed by VLDL receptors, but in chronic uremia, the expression of VLDL receptors in tissues is also downregulated [23]. This makes impossible the VLDL binding with VLDL receptors in adipocytes and myocytes and their removal from the circulation (Figure 4). Insulin resistance is often associated with chronic uremia and seems to be responsible for a hepatic VLDL overproduction [24]. Secondary hyperparathyroidism, in renal failure, may play an additional role in triglyceride-rich lipoprotein catabolism impairment.
Changes in chylomicrons and VLDL metabolism in renal failure.
The predominant mechanism responsible for delayed metabolism of chylomicrons and very-low-density lipoproteins is increased synthesis apolipoprotein (Apo B-48) and low activity of lipoprotein lipase (LPL). Decrease concentration of high-density lipoproteins in renal failure results with decreased Apo E and Apo C-II, which are necessary for activation of LPL and for uptakes of remnant chylomicrons and intermediate-density lipoproteins by a receptor specific for Apo E. Such defect, together with the downregulation of LDL receptor protein and hepatic lipase (HL), leads to accumulation of chylomicron remnants and IDL, reducing the release of fatty acids into peripheral tissues. In physiological conditions, surplus IDL is transformed into LDL by the removal of their triglycerides and enrichment in cholesteryl esters from HDL-2 by CETP. But the lack of HDL-2 impedes this process and leads to the accumulation of pro-atherogenic IDL. Increased activity of CETP contributed in reducing HDL concentration. The presence of lipoprotein lipase inhibitor, Apo C-III, also contributes to delayed triglyceride-rich lipoprotein metabolism.
Uremic patients have decreased HDL in comparison with healthy population [25, 26]. Several mechanisms, working in concern, may underlie the reduction in HDL levels, which is usually indicative of impaired reverse cholesterol transport. Specifically, maturation of HDL is impaired and its composition is altered. Thus, uremic patients usually exhibit decreased levels of apolipoproteins A-I and A-II (the main protein constituents of HDL), diminished activity of LCAT, the enzyme responsible for the esterification of free cholesterol in HDL particles, as well as increased activity of CETP that facilitates the transfer of cholesterol esters from HDL to triglyceride-rich lipoproteins. One of the mechanisms for impaired HDL metabolism in uremia is the increased activity of enzyme ACAT which is responsible for intracellular cholesterol esterification. In physiological conditions, Apo A-I and Apo A-II, in the circulation, are loaded with cholesterol and phospholipids to form nascent HDL. Then, nascent HDL binds to the ABCA-1 receptor on circulating macrophages and activates cholesterol ester hydrolase allowing their loading with cholesterol. ACAT limits this reverse efflux of cholesterol from macrophages by catalyzing the esterification of intracellular cholesterol. Oxidative modification of Apo A-I can limit HDL binding on macrophages [27] and upregulation of hepatic ACAT [28] contributing in impaired cholesterol efflux. Therefore, an increase in ACAT activity can potentially limit HDL-mediated cholesterol uptake and contribute to the reduction in plasma HDL cholesterol and impaired maturation of HDL. Although the effect of chronic renal failure on ACAT expression and activity in the extrahepatic tissues is not known, chronic renal failure has been recently shown to markedly raise hepatic ACAT-2 mRNA and protein abundance, as well as total ACAT activity [29].
On the other hand, the activity of enzyme LCAT is decreased [30, 31]. Apo A-I is the activator of LCAT, the essential enzyme for the HDL-mediated cholesterol retrieval from extrahepatic tissues and as well as ligand for the SR-B1 and HDL-binding protein (ABCA1 transporter). Apo A-II serves as an activator of hepatic lipase, which plays a central role in the removal of HDL triglycerides by the liver. As mentioned above, in patients with impaired kidney function, Apo A-I and Apo A-II levels are decreased. This reduction contributes to diminished HDL concentration and impaired HDL maturation. Until recently, it was not clear whether the reported reduction in plasma LCAT activity is caused by the reduction in its hepatic production and plasma concentration or is a consequence of its inhibition by an unknown uremic toxin [32]. Another enzyme with diminished activity is CETP. The enzyme mediates transfer of cholesterol ester from HDL to IDL in exchange for triglycerides. Increased activity of CETP in uremic patients facilitates the transfer of cholesterol esters from HDL to triglyceride-rich lipoproteins, reducing the HDL cholesterol ester and elevation of HDL triglycerides. The mechanism responsible for the elevation of CETP is unknown, but some investigation connected its increased synthesis with proteinuria. Probably the same mechanism is responsible for the dysregulation of hepatic SR-B1. Hepatic SR-B1 is the primary pathway for the disposal of HDL-borne cholesterol ester and triglycerides, and dysregulation of this protein can impact HDL metabolism. Heavy glomerular proteinuria has been shown to significantly reduce hepatic SR-B1 protein expression in experimental animals [29]. HDL has a protective effect against inflammation, platelet adhesion, and LDL oxidation. Those protective functions of HDL can be attributed to HDL-associated enzymes on its surface. Paraoxonase-1 is considered as the main antioxidant enzyme bound to HDL. Mainly expressed in the liver and the kidney, this enzyme exhibited antioxidant properties against lipid peroxidation as it binds to HDL and in a minor part to VLDL [33]. Glutathione seleno-peroxidase 3, also known as glutathione peroxidase 3, is another antioxidant enzyme associated with HDL [34].
One of main anti-atherogenic properties of HDL is a reverse cholesterol transport from circulating macrophages. HDL also increases the production of nitric oxide (NO), through the activation of the endothelial NO synthase in endothelial cells resulting in a vasorelaxant phenotype. In CKD the production of NO by endothelial cells is significantly reduced with HDL [28]. HDL also inhibits the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1), which prevent the attachment of circulating monocytes to endothelial cells. In uremic patients, HDL promotes an enhanced expression of VCAM-1 and ICAM-1 on endothelial cells [35, 36]. Moreover, CKD-HDL upregulates the expression of pro-inflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1), interleukin-1ß (IL-1ß), and tumor necrosis factor α (TNF-α) [36, 37]. And finally normal HDL exhibit anti-apoptotic effects on endothelial cells through the downregulation of caspase-3 (a member of the cysteine-aspartic acid protease) activity [38]. All these diminished protective functions of HDL can contribute to accelerated atherogenesis [39]. HDL is very sensitive in oxidative stress and posttranslational modifications. Renal failure is associated with an enhanced activity of enzyme myeloperoxidase (MPO, EC 1.11.2.2) that plays a crucial role in the generation of posttranslational modification derived products (PTMDPs). MPO catalyzed the oxidative reactions and formation of a variety of chlorinated protein and lipid adducts. MPO-modified ApoA-1 results in decreased reverse cholesterol efflux and a reduced binding with ABCA-1 receptor, which disturbed cholesterol homeostasis (Figure 5). 3-chlorotyrosine, an oxidation product of MPO, impairs the activity of enzymes, LCAT, and PON-1, resulting with decreased anti-inflammatory effects of HDL. And through the activation of SR-B1 in macrophages, MPO-modified HDL directly contributes in atherosclerosis (Figure 5).
HDL metabolism in renal failure.
In renal failure, decreased activity of lecithin-cholesterol acyltransferase impaired the transformation of nascent cholesterol into HDL3 and then into HDL2. Increased activity of cholesteryl ester transfer protein facilitates the transfer of cholesterol esters from HDL to triglyceride-rich lipoproteins, reducing HDL concentration. Removal of free cholesterol from macrophages proceeds by scavenger receptor 1. Nascent HDL is generated when Apo A-I interacts with ATP-binding cassette transporter type 1 (ABCA1). Than nascent HDL activates cholesterol ester hydrolase allowing their loading with cholesterol. ACAT limits this reverse efflux of cholesterol from macrophages by catalyzing the esterification of intracellular cholesterol. Increased activity of ACAT, in renal failure, participates in impaired cholesterol efflux. Antioxidative and anti-inflammatory functions of HDL are impaired due to reduced activity of HDL enzyme PON1. HDL from patients with renal failure loses its vasoprotective properties, inhibiting nitric oxide production. Oxidative modification of Apo A-I decreases HDLs binding to macrophages. Myeloperoxidase-modified Apo A-I decrease reverse cholesterol efflux, reduce binding with ABCA1, and impair HDLs anti-apoptotic properties.
Beyond atherogenic risk of LDL level itself, renal failure leads to various structural modifications of LDL particles. The lipoproteins found in uremic patients are disproportionately modified, with LDL that is enriched in triglycerides. These modified LDL particles tend to be smaller and denser in their form. Small dense LDL is believed to be markedly pro-atherogenic, and this is attributed to its ability to infiltrate the vessel wall and its increased susceptibility to oxidative modification. Because of the significantly modified lipid subfraction turnover, residence time of lipoproteins in the circulation is prolonged. Thus, lipoproteins are at risk of posttranslational modification. LDL receptor-mediated cholesterol uptake plays an important role in cholesterol homeostasis. Modified LDL have reduced affinity for the classic LDL receptors and are taken up by the scavenger receptors on the surface of the macrophages. These receptors are increased in chronic uremia. High affinity for macrophages results in the accumulation of cholesterol and the formation of foam cells in the vascular walls, resulting in the development of atherosclerotic plaques [40, 41]. Heavy proteinuria alone or in combination with chronic uremic state results in acquired LDL receptor deficiency and plays a central role in the genesis of the atherosclerosis and cardiovascular diseases. Several levels of LDL oxidation can coexist in the bloodstream and lead to the activation of several pathways involved in atherosclerosis through their binding to scavenger receptors [42] and smooth muscle cell proliferation. There is an evidence that OxLDL are accumulated in uremic patients and are correlated with the intensity of peripheral arterial disease [43]. Oxidized epitopes of LDL can activate immunity and then lead to the formation of antibodies directed against OxLDL. OxLDL/antibodies against OxLDL ratio were also correlated with carotid atherosclerosis and cardiovascular events [44]. Formation of OxLDL is a consequence of oxidative stress. As mentioned above, the breakdown of polyunsaturated fatty acids produces highly reactive molecules, such as MDA and 4-OH-2,3 alkenals. MDA and 4-OH-2,3 alkenals can form Schiff bases and covalent Michael-type adducts, with lysine residues of Apo B-100, in LDL (Figure 6). The oxidized fatty acid fragments which can remain attached via ester bridges, may also contain terminal reactive phospholipids which may form adducts with Schiff base lysine residues of Apo B-100. Similarly with HDL modifications, increased levels of MPO are involved in LDL modifications. MPO can modify LDL through several mechanisms. MPO initiated the reaction between hypochlorous acid and tyrosine residues of Apo B-100, protein part of LDL, resulting with 3-chlorotyrosine formation, which is known for pro-atherogenic properties through its binding with lectin-like oxidized LDL receptor 1. MPO also generated reactive nitrogen species, converting LDL into a nitrosilated-LDL form. This reaction resulted in nitration of Apo B-100 tyrosyl residues of LDL. Carbamylated LDL (cLDL) is another modified form of LDL, initiated by MPO. In this reaction MPO catalyzed the addition of thiocyanate, derived from the decomposition of urea to the lysine residues of LDL, and leads to the formation of carbamylated LDL [45, 46]. The carbamylation occurs by spontaneous, nonenzymatic chemical modification of Apo B-100, by thiocyanate. It is a irreversibly reaction of thiocyanate with free amino groups and ε-NH2 of lysine residues in protein part of LDL (Figure 7). cLDL have pro-atherogenic effects such as the transformation of macrophages into foam cells [47] through their binding to the pro-atherogenic CD36 receptor [48, 49]. cLDL are associated with endothelial toxicity [50, 51] through lectin-like oxidized LDL receptor 1 [52] (Figure 8). cLDL levels are raised by chronic uremia [53, 54].
Formation of oxidized LDL.
Formation of carbamylated LDL.
Oxidized LDL and carbamylated LDL effects.
Modified forms of LDL; carbamylated LDL and oxidized LDL; activated lectin-like oxidized LDL receptor 1, on endothelial cells; and initiated formation of macrophages and smooth muscle cell proliferation.
The contribution of cardiovascular events to the extraordinary high mortality in CKD has generated some interest in nontraditional atherosclerotic cardiovascular disease risk factors, which are prevalent in this population, such as Lipoprotein (a) [Lp (a)]. Lp (a) is an LDL-like lipoprotein containing a unique apolipoprotein called Apo(a). Serum levels of Lp(a) are determined largely by genetic variation in the gene encoding for Apo(a). Apo(a) is very homologous to plasminogen [55] and exhibits an extreme size polymorphism with the Apo(a) isoproteins, ranging in size from 420 to 840 kDa. Inherited in an autosomal codominant fashion, the Apo(a) isoprotein is closely correlated with serum Lp(a) concentrations, with an inverse correlation between the size of the Apo(a) isoprotein and the serum Lp(a) concentrations. Lp(a) has been implicated in the regulation of plasminogen activator inhibitor-1 expression in endothelial cells and shown to inhibit endothelial cell surface fibrinolysis to attenuate plasminogen binding to platelets and to bind to plaque matrix components. Autopsy studies in humans have documented the presence of Lp(a) in aortic and coronary atherosclerotic plaques and an apparent colocalization with fibrinogen [56]. Lp(a) levels are frequently elevated in uremic patients with CKD [57] and have been associated with a frequency distribution of apolipoprotein (a)-Lp(a) isoforms, similar to those found in general population. This indicates that elevated Lp(a) levels in these patients are not due to the genetic origin [58]. It has been suggested that kidneys have an important role in Lp(a) metabolism [59]. In CKD, Lp(a) occurs at high concentrations, largely because of reduced clearance or as a result of increased hepatic synthesis, induced by an acute-phase reaction or by protein losses from proteinuria [60]. Uremia can be considered to be a state of activated acute-phase response, and in the micro-inflammatory milieu, a number of atherogenic proteins like Lp(a) are acting as an acute-phase reactant. Based in all these properties, Lp(a) is a prototype candidate to be classified as a uremic toxin.
Chronic uremia causes profound alteration in lipoprotein metabolism, promoting the development of atherosclerosis and cardiovascular disease. Besides the changes in their concentration, enhanced oxidative stress and uremic environment can strongly modify circulating lipoproteins leading to profound alterations of their biological properties and can be considered as uremic toxins. Uremic lipoprotein profile is directly involve in glomerular capillary endothelial damage and in the progression of renal disease. This “reverse epidemiology” shows the importance of lipid control to prevent the progression of renal failure.
The authors declare no conflict of interest.
ABCA1 | ATP-binding cassette transporter type I |
ACAT | acyl-CoA cholesterol acyltransferase |
α-TNF | alpha tumor necrosis factor |
ALEs | advanced lipoxidation end products |
Apo A,B,C,E | apolipoprotein A,B,C,E |
Apo (a) | apolipoprotein |
CETP | cholesteryl ester transfer protein |
CKD | chronic kidney disease |
cLDL | carbamylated low-density lipoprotein |
DGAT | acyl-CoA diacylglycerol acyltransferase |
GPX | glutathione peroxidase |
GPX3 | glutathione peroxidase 3 |
HDL | high-density lipoproteins |
IDL | intermediate-density lipoproteins |
ICAM-1 | intercellular adhesion molecule-1 |
IL-1ß | interleukin-1ß |
LCAT | lecithin-cholesterol acyltransferase |
LDL | low-density lipoproteins |
Lp(a) | lipoprotein (a) |
LRP | LDL related protein |
MCP-1 | monocyte chemoattractant protein-1 |
mRNA | messenger ribonucleic acid |
MDA | malondialdehyde |
MPO | myeloperoxidase |
NO | nitric oxide |
OxLDL | oxidized-LDL |
LCFA | long chains fatty acids |
LOO• | peroxyl radicals |
LOOH | lipid hydroperoxide |
PON1 | paraoxonase 1 |
PTMDPs | posttranslational modification derived products |
PUFAs | polyunsaturated fatty acids |
ROS | reactive oxygen species |
SOD | superoxide dismutase |
SR-B1 | scavenger receptor B1 |
VCAM | vascular adhesion molecule-1 |
VLDL | very-low-density lipoprotein |
IntechOpen publishes different types of publications
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\\n\\nPERSPECTIVE CHAPTER – A perspective chapter offers a new point of view on existing problems, fundamental concepts, or common opinions on a specific topic. Perspective chapters can propose or support new hypotheses, or discuss the significance of newly achieved innovations. Perspective chapters can focus on current advances and future directions on a topic and include both original data and personal opinion.
\\n\\nINTRODUCTORY CHAPTER – An introductory chapter states the purpose and goals of the book. The introductory chapter is written by the Academic Editor.
\\n\\nMonographs is a self-contained work on a particular subject, or an aspect of it, written by one or more authors. Monographs usually have between 130 and 500 pages.
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\\n\\nCollection of papers presented at conferences, workshops, symposiums, or scientific courses, published in book format
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We characterized the optical wireless communication channel through the channel measurements and present different models for the OWC link performance evaluations. In addition, we present some technologies for the OWC performance enhancement in order to address the last-mile transmission bottleneck of the system efficiently. The technologies can be of great help in alleviating the stringent requirement by the cloud radio access network (C-RAN) backhaul/fronthaul as well as in the evolution toward an efficient backhaul/fronthaul for the 5G network. Furthermore, we present a proof-of-concept experiment in order to demonstrate and evaluate high capacity/flexible coherent PON and OWC links for different network configurations in the terrestrial links. To achieve this, we employ advanced modulation format and digital signal processing (DSP) techniques in the offline and real-time mode of the operation. 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Further, the improved dual circularly polarized (CP) omnidirectional antenna based on slot array in coaxial cylinder structure is presented too, and two ports are assigned in its two side as left hand circularly polarized (LHCP) port and right hand circularly polarized (RHCP) port, respectively. The simulation and experiment results show their novelty and good performance of omnidirectional circular polarization with about 5 dBi gain in 5.2–5.9 GHz.",book:{id:"5427",slug:"modern-antenna-systems",title:"Modern Antenna Systems",fullTitle:"Modern Antenna Systems"},signatures:"Bin Zhou, Junping Geng, Xianling Liang, Ronghong Jin and\nGuanshen Chenhu",authors:[{id:"147056",title:"Prof.",name:"Xian-Ling",middleName:null,surname:"Liang",slug:"xian-ling-liang",fullName:"Xian-Ling Liang"},{id:"189327",title:"Prof.",name:"Junping",middleName:null,surname:"Geng",slug:"junping-geng",fullName:"Junping Geng"},{id:"189923",title:"Prof.",name:"Ronghong",middleName:null,surname:"Jin",slug:"ronghong-jin",fullName:"Ronghong Jin"},{id:"189925",title:"MSc.",name:"Bin",middleName:null,surname:"Zhou",slug:"bin-zhou",fullName:"Bin Zhou"},{id:"189927",title:"MSc.",name:"Guanshen",middleName:null,surname:"Chenhu",slug:"guanshen-chenhu",fullName:"Guanshen Chenhu"}]}],onlineFirstChaptersFilter:{topicId:"762",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",slug:"christian-palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. Dr. Serra\\'s current projects are soil organic matter, soil phosphorus fractions, compositional nutrient diagnosis (CND) and isometric log ratio (ilr) transformation in compositional data analysis.",institutionString:"Brazilian Agricultural Research Corporation",institution:{name:"Brazilian Agricultural Research Corporation",country:{name:"Brazil"}}}]}},subseries:{item:{id:"93",type:"subseries",title:"Inclusivity and Social Equity",keywords:"Social contract, SDG, Human rights, Inclusiveness, Equity, Democracy, Personal learning, Collaboration, Glocalization",scope:"