Selected publications in the field of lipid self-spreading/wetting
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5609",leadTitle:null,fullTitle:"Phenolic Compounds - Biological Activity",title:"Phenolic Compounds",subtitle:"Biological Activity",reviewType:"peer-reviewed",abstract:"Phenolic compounds comprise a broad class of natural products formed mainly by plants, but also microorganisms and marine organisms that have the capacity to form them. Nowadays the interest in these compounds has increased mainly due to their diverse chemical structure and wide biological activity valuable in the prevention of some chronic or degenerative diseases. The functional foods are a rich source of these phytochemicals, and this is the starting point for this book, which shows the state of the art of the phenolic compounds and their biological activity. This book integrates eleven chapters that show the state of the art of diverse biological activity of the phenolic compounds, present in some crops or fruits.",isbn:"978-953-51-2960-8",printIsbn:"978-953-51-2959-2",pdfIsbn:"978-953-51-5090-9",doi:"10.5772/63693",price:119,priceEur:129,priceUsd:155,slug:"phenolic-compounds-biological-activity",numberOfPages:238,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"008b92507ee2f757322ec4565e631bb5",bookSignature:"Marcos Soto-Hernandez, Mariana Palma-Tenango and Maria del Rosario Garcia-Mateos",publishedDate:"March 8th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5609.jpg",numberOfDownloads:36014,numberOfWosCitations:244,numberOfCrossrefCitations:164,numberOfCrossrefCitationsByBook:9,numberOfDimensionsCitations:354,numberOfDimensionsCitationsByBook:12,hasAltmetrics:1,numberOfTotalCitations:762,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 1st 2016",dateEndSecondStepPublish:"June 22nd 2016",dateEndThirdStepPublish:"September 18th 2016",dateEndFourthStepPublish:"December 17th 2016",dateEndFifthStepPublish:"February 15th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"65790",title:"Prof.",name:"Marcos",middleName:null,surname:"Soto-Hernández",slug:"marcos-soto-hernandez",fullName:"Marcos Soto-Hernández",profilePictureURL:"https://mts.intechopen.com/storage/users/65790/images/system/65790.jpg",biography:"Dr. Marcos Soto Hernández is a pharmacist from the National University of México. He has obtained his PhD from the University of Wales Cardiff UK and he is now a full time Professor at Colegio de Postgraduados where conducts research in phytochemistry and bioactivity natural products. He has established collaboration with research groups in UK, The Netherlands, Spain and others groups in México. He has received several awards locally and abroad. Today his main line of research is the bio-guided isolation of secondary metabolites with importance in medicine and agriculture (the potential of the local aromatic plants are part of his recent research). He has published more than 150 research papers and several book chapters and conference proceedings. He is member of several professional societies (national or international).",institutionString:"Colegio de Postgraduados",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Colegio de Postgraduados",institutionURL:null,country:{name:"Mexico"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"193077",title:"Dr.",name:"Mariana",middleName:null,surname:"Palma-Tenango",slug:"mariana-palma-tenango",fullName:"Mariana Palma-Tenango",profilePictureURL:"https://mts.intechopen.com/storage/users/193077/images/system/193077.jpg",biography:"Dr. Mariana Palma-Tenango is an engineer agronomist from the Universidad Autónoma Chapingo and holds a PhD degree in Plant Physiology from the Colegio de Postgraduados, México. Dr. Tenango has teaching duties in the National Autonomous University of Mexico, and is an assistant professor of Phytochemistry at the Colegio de Postgraduados. She has participated in the organization of meetings and symposiums in México and is a supervisor of master and PhD degree students. Her research line is phytochemistry, medicinal, and aromatic plants.",institutionString:"Colegio de Postgraduados",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Colegio de Postgraduados",institutionURL:null,country:{name:"Mexico"}}},coeditorTwo:{id:"194366",title:"Dr.",name:"Rosario",middleName:null,surname:"García-Mateos",slug:"rosario-garcia-mateos",fullName:"Rosario García-Mateos",profilePictureURL:"https://mts.intechopen.com/storage/users/194366/images/system/194366.jpg",biography:"Dr. María del Rosario García-Mateos is a full Professor cat the Universidad Autónoma Chapingo, in Texcoco, Estado de México, Mexico. and holds a PhD degree from the Colegio de Postgraduados, Mexico. Her research line is related with the nutraceutical properties and biological activity of horticultural crops. She has supervised master and PhD thesis, has published more than 71 papers, and has been a reviewer of several scientific journals.",institutionString:"Universidad Autonoma Chapingo",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"500",title:"Phytochemistry",slug:"organic-chemistry-phytochemistry"}],chapters:[{id:"53128",title:"Phenolic Compounds: Functional Properties, Impact of Processing and Bioavailability",doi:"10.5772/66368",slug:"phenolic-compounds-functional-properties-impact-of-processing-and-bioavailability",totalDownloads:9318,totalCrossrefCites:75,totalDimensionsCites:142,hasAltmetrics:0,abstract:"In this chapter, we discuss the influence of the processing methods on the content of phenolic compounds in fruits and vegetables. The intake of fruits and vegetables based‐foods are associated with delayed aging and a decreased risk of chronic disease development. Fruits and vegetables can be consumed in natura, but the highest amounts are ingested after some processing methods, such as cooking procedures or sanitizing methods. These methods are directly methods are directly related to alteration on the phenolic content. In addition, the postharvest conditions may modify several phytochemical substances. Phenolic compounds are referred to as phytochemicals found in a large number of foods and beverages. The relative high diversity of these molecules produced by plants must be taken into account when methods of preparation are employed to obtain industrial or homemade products. Phenolic compounds comprise one (phenolic acids) or more (polyphenols) aromatic rings with attached hydroxyl groups in their structures. Their antioxidant capacities are related to these hydroxyl groups and phenolic rings. Despite the antioxidant activity, they have many other beneficial effects on human health. However, before attributing health benefits to these compounds, absorption, distribution, and metabolism of each phenolic compound in the body are important points that should be considered.",signatures:"Igor Otavio Minatel, Cristine Vanz Borges, Maria Izabela Ferreira,\nHector Alonzo Gomez Gomez, Chung-Yen Oliver Chen and\nGiuseppina Pace Pereira Lima",downloadPdfUrl:"/chapter/pdf-download/53128",previewPdfUrl:"/chapter/pdf-preview/53128",authors:[{id:"146379",title:"Dr.",name:"Giuseppina",surname:"Lima",slug:"giuseppina-lima",fullName:"Giuseppina Lima"},{id:"194002",title:"MSc.",name:"Cristine",surname:"Vanz Borges",slug:"cristine-vanz-borges",fullName:"Cristine Vanz Borges"},{id:"194003",title:"Prof.",name:"Igor Otavio",surname:"Minatel",slug:"igor-otavio-minatel",fullName:"Igor Otavio Minatel"},{id:"194004",title:"Dr.",name:"Maria Izabela",surname:"Ferreira",slug:"maria-izabela-ferreira",fullName:"Maria Izabela Ferreira"},{id:"194005",title:"Prof.",name:"Hector",surname:"Gomez-Gomez",slug:"hector-gomez-gomez",fullName:"Hector Gomez-Gomez"},{id:"194006",title:"Prof.",name:"Chung-Yen Oliver",surname:"Chen",slug:"chung-yen-oliver-chen",fullName:"Chung-Yen Oliver Chen"}],corrections:null},{id:"53885",title:"The Relationship Between Phenolic Compounds from Diet and Microbiota",doi:"10.5772/66908",slug:"the-relationship-between-phenolic-compounds-from-diet-and-microbiota",totalDownloads:2338,totalCrossrefCites:2,totalDimensionsCites:7,hasAltmetrics:0,abstract:"All multicellular organisms live in a strong bond with the microorganisms from around the world, and the humans are not the exceptions. Human microbiota (a complex bacterial community) contains about 1014 microbial cells, 10 times more than the content of the cells from our body and the microbial genome named microbiome, 1000 more that the human genome. It colonises any surface of the human body, above our skin, in the genitourinary tract, gut and airways. From all this, the gut is the most colonised organ, with an amount of almost 70% of the human microbes. Considering the large size of the gut, compared with a tennis terrain, filled with substances that plays a key, nutritive role for the microbes, polyphenols are micronutrients from our diet, with an emerging role in the modulation of the colonic microbial population composition and activity. Therefore, many studies underline that long-term consumption of diets rich in plants polyphenols offers protection against cancer, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. This chapter reviews the biological effects of plant polyphenols in the context of relevance to human health, especially considering the food functionality area, together with the complexity of the human microbiota and the bioavailability highly dependent on their intestinal absorption.",signatures:"Daniela Elena Popa, Cristina Manuela Drăgoi, Andreea Letiţia\nArsene, Ion Bogdan Dumitrescu, Alina Crenguţa Nicolae, Bruno Stefan Velescu and\nGeorge T.A. Burcea-Dragomiroiu",downloadPdfUrl:"/chapter/pdf-download/53885",previewPdfUrl:"/chapter/pdf-preview/53885",authors:[{id:"190111",title:"Dr.",name:"Andreea",surname:"Arsene",slug:"andreea-arsene",fullName:"Andreea Arsene"},{id:"192919",title:"Associate Prof.",name:"Cristina Manuela",surname:"Drăgoi",slug:"cristina-manuela-dragoi",fullName:"Cristina Manuela Drăgoi"},{id:"193026",title:"Dr.",name:"Daniela Elena",surname:"Popa",slug:"daniela-elena-popa",fullName:"Daniela Elena Popa"},{id:"193027",title:"Dr.",name:"George Traian Alexandru",surname:"Burcea Dragomiroiu",slug:"george-traian-alexandru-burcea-dragomiroiu",fullName:"George Traian Alexandru Burcea Dragomiroiu"},{id:"193030",title:"Mrs.",name:"Alina Crenguta",surname:"Nicolae",slug:"alina-crenguta-nicolae",fullName:"Alina Crenguta Nicolae"},{id:"195925",title:"Mr.",name:"Ion Bogdan",surname:"Dumitrescu",slug:"ion-bogdan-dumitrescu",fullName:"Ion Bogdan Dumitrescu"},{id:"198528",title:"Dr.",name:"Bruno Ștefan",surname:"Velescu",slug:"bruno-stefan-velescu",fullName:"Bruno Ștefan Velescu"}],corrections:null},{id:"53580",title:"Application of Phenolic Compounds for Food Preservation: Food Additive and Active Packaging",doi:"10.5772/66885",slug:"application-of-phenolic-compounds-for-food-preservation-food-additive-and-active-packaging",totalDownloads:3906,totalCrossrefCites:23,totalDimensionsCites:49,hasAltmetrics:0,abstract:"Phenolic compounds are well known for their health benefits related to antioxidant activity. In addition, this kind of compounds can be extracted from natural sources, such as olives, grapes, fruits, vegetables, rice, spices, herbs, tea and algae, among others. In this way, these compounds have increased their popularity and, little by little, the consumers are more interested in these compounds due to the fact that they come from natural sources and because they have health biological activity. In fact, other important characteristics associated to phenolic compounds are the antimicrobial activity, because phenolics have the capacity of retarding the microbial invasion in some products and avoiding the putrefaction of others, mainly fruits and vegetables. These properties allow phenolic compounds to be suitable for numerous food preservation applications. Therefore, different kinds of products can be fortificated with phenolic compounds to extend the shelf life of some foods, to turn them in functional food or to incorporate them in food packaging. Active packing is an innovative strategy where phenolic compounds can play an important role for improving the global assessment and extend the shelf life of commercial products.",signatures:"Sara Martillanes, Javier Rocha-Pimienta, Manuel Cabrera-Bañegil,\nDaniel Martín-Vertedor and Jonathan Delgado-Adámez",downloadPdfUrl:"/chapter/pdf-download/53580",previewPdfUrl:"/chapter/pdf-preview/53580",authors:[{id:"193618",title:"Dr.",name:"Jonathan",surname:"Delgado-Adámez",slug:"jonathan-delgado-adamez",fullName:"Jonathan Delgado-Adámez"},{id:"193962",title:"Ms.",name:"Sara",surname:"Martillanes",slug:"sara-martillanes",fullName:"Sara Martillanes"},{id:"193963",title:"Mr.",name:"Javier",surname:"Rocha-Pimienta",slug:"javier-rocha-pimienta",fullName:"Javier Rocha-Pimienta"},{id:"193964",title:"Mr.",name:"Manuel",surname:"Cabrera-Bañegil",slug:"manuel-cabrera-banegil",fullName:"Manuel Cabrera-Bañegil"},{id:"193965",title:"Dr.",name:"Daniel",surname:"Martín",slug:"daniel-martin",fullName:"Daniel Martín"}],corrections:null},{id:"53658",title:"Phenolic Antioxidant Capacity: A Review of the State of the Art",doi:"10.5772/66897",slug:"phenolic-antioxidant-capacity-a-review-of-the-state-of-the-art",totalDownloads:3206,totalCrossrefCites:13,totalDimensionsCites:30,hasAltmetrics:1,abstract:"There are many evidences pointing to oxidative stress as the promoter of the development of many degenerative diseases such as cancer, cardiovascular diseases, and neurodegeneration. It has been suggested that a diet rich in antioxidants would be beneficial to human health. To determine the antioxidant capacity of the different sources of antioxidants, they have different chemical methods used, in vitro cells, laboratory animals, and recently nanoparticles. This chapter provides an account of the main antioxidant evaluation methods applied to phenolic compounds, recounting their advantages and disadvantages, as well as a reflection on the parameters that should always care to obtain reproducible results.",signatures:"Rubén San Miguel-Chávez",downloadPdfUrl:"/chapter/pdf-download/53658",previewPdfUrl:"/chapter/pdf-preview/53658",authors:[{id:"193235",title:"M.Sc.",name:"Ruben",surname:"San Miguel",slug:"ruben-san-miguel",fullName:"Ruben San Miguel"}],corrections:null},{id:"53564",title:"Plant Phenolic Compounds as Immunomodulatory Agents",doi:"10.5772/66112",slug:"plant-phenolic-compounds-as-immunomodulatory-agents",totalDownloads:2818,totalCrossrefCites:10,totalDimensionsCites:20,hasAltmetrics:1,abstract:"Immunology is a source of continuous discoveries; Immunology was and still is a source of continuous discoveries. Immunomodulation encompasses all therapeutic interventions aimed at modifying the immune response. Immunostimulation is desirable to prevent infection in states of immunodeficiency and to fight infections and cancer. On the other hand, immunosuppressive agents inhibit the activity of the immune system, and they are used to prevent the rejection of transplanted organs and tissues and to treat autoimmune diseases or diseases that are most likely of autoimmune origin (e.g., rheumatoid arthritis, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, etc.), or other nonautoimmune inflammatory diseases (e.g., allergic asthma). The discovery of immunomodulatory agents from medicinal plants devoid of toxic side effects, with enhanced bioavailability and that can be used for a long duration, is of great actuality. Research on natural immunomodulators provides a therapeutic solution that addresses a multitude of disorders. Plant phenolic compounds already proved beneficial effects in cardiovascular diseases, diabetes, and cancer, exerting mainly antioxidant and anti-inflammatory effects. The concepts of “immunomodulatory,” “anti-inflammatory,” and “antioxidant” are often strongly related, and a review of phenolic compound action on immune system should be analyzed in a context, revealing their mechanism of action on effector cells and also on the system as a whole.",signatures:"Alice Grigore",downloadPdfUrl:"/chapter/pdf-download/53564",previewPdfUrl:"/chapter/pdf-preview/53564",authors:[{id:"193003",title:"Dr.",name:"Alice",surname:"Grigore",slug:"alice-grigore",fullName:"Alice Grigore"}],corrections:null},{id:"53576",title:"Inhibitory Properties of Phenolic Compounds Against Enzymes Linked with Human Diseases",doi:"10.5772/66844",slug:"inhibitory-properties-of-phenolic-compounds-against-enzymes-linked-with-human-diseases",totalDownloads:2633,totalCrossrefCites:14,totalDimensionsCites:40,hasAltmetrics:0,abstract:"Some drugs currently used are inhibitors of enzymes involved in mediating many disease processes. Concerns over the toxicity and side effects of synthetic enzyme inhibitors have led to a search for new safe and effective inhibitors particularly from natural sources. Owing to their wide range of biological effects, plant phenolic compounds are one of the most studied families of natural products. This chapter aims to provide an overview of the potential of phenolic compounds as enzyme inhibitors. Extensive research has been conducted to study the enzyme inhibitory capacity of many phenolic compounds against several enzymes linked with important human conditions. Investigations conducted are mainly focused on the inhibition of angiotensin I-converting enzyme, α-amylase and α-glucosidase, lipase, cholinesterases, proinflammatory enzymes (cyclooxygenases and 5-lipoxygenase) and tyrosinase, which are related with hypertension, type II diabetes, obesity, Alzheimer’s diseases, inflammation and skin hyperpigmentation, respectively. Overall, among phenolics, flavonoids are probably those with great capacity to inhibit the activity of the enzymes revised. Several studies demonstrated the potent antioxidant and anti-inflammatory properties of flavonoids, which highlight the therapeutic potential of these compounds. Although our literature survey showed that a huge number of phenolic compounds have been studied and there are some promising compounds depending on the enzyme, more in vivo tests and subsequent steps to be a drug candidate are required before therapeutic application.",signatures:"Sandra Gonçalves and Anabela Romano",downloadPdfUrl:"/chapter/pdf-download/53576",previewPdfUrl:"/chapter/pdf-preview/53576",authors:[{id:"193464",title:"Prof.",name:"Anabela",surname:"Romano",slug:"anabela-romano",fullName:"Anabela Romano"},{id:"193968",title:"Dr.",name:"Sandra",surname:"Gonçalves",slug:"sandra-goncalves",fullName:"Sandra Gonçalves"}],corrections:null},{id:"53840",title:"Grape Seed Nutraceuticals for Disease Prevention: Current Status and Future Prospects",doi:"10.5772/66894",slug:"grape-seed-nutraceuticals-for-disease-prevention-current-status-and-future-prospects",totalDownloads:2563,totalCrossrefCites:3,totalDimensionsCites:11,hasAltmetrics:0,abstract:"Grapes (Vitis spp.) are consumed as fresh table fruits, raisins, and processed into wine, juice, jelly and other value-added products. Grapes contain bioactive secondary metabolites (polyphenols), such as proanthocyanins (oliogemeric flavonoids), flavonoids (catechin, epicatechin, and quercetin), and anthocyanins. They have non-flavonoids such as hydroxycinnamic acids (p-coumaric, cinnamic, caffeic, gentisic, ferulic, and vanillic acids), and hydroxybenzoic acids: trihydroxy stilbenes (resveratrol and polydatin). These phytochemicals are of economic importance to pharmaceutical, food and cosmetic industries. Nutraceuticals from grape seeds have potential cardioprotective, anti-cancer, antioxidant, anti-inflammatory, antiviral, neuroprotective, hepatoprotective and antimicrobial properties. Grape seed nutraceuticals have been re-invented in the past few years as a new paradigm in human medicine. In particular, nutraceuticals from grape seeds have been used in stopping wound bleeding, anti-inflammatory agents, pain relief, and anti-diarrhea. In addition, they can be used for the treatment of various human health conditions such as cancer, cholera, smallpox, and nausea as well as eye infections, skin, kidney, liver diseases, etc. Nowadays, consumers are demanding for healthy supplements and personal care products with natural ingredients. Therefore, the present review highlights recent developments and future opportunities of grape seed nutraceuticals for the prevention of human diseases.",signatures:"Anthony Ananga, James Obuya, Joel Ochieng and Violeta Tsolova",downloadPdfUrl:"/chapter/pdf-download/53840",previewPdfUrl:"/chapter/pdf-preview/53840",authors:[{id:"74792",title:"Dr.",name:"Joel W.",surname:"Ochieng",slug:"joel-w.-ochieng",fullName:"Joel W. Ochieng"},{id:"126149",title:"Dr.",name:"Anthony",surname:"Ananga",slug:"anthony-ananga",fullName:"Anthony Ananga"},{id:"137412",title:"Dr.",name:"Violetka",surname:"Tsolova",slug:"violetka-tsolova",fullName:"Violetka Tsolova"},{id:"193798",title:"Dr.",name:"James",surname:"Obuya",slug:"james-obuya",fullName:"James Obuya"}],corrections:null},{id:"53180",title:"Phenolic Compounds with Anti-virulence Properties",doi:"10.5772/66367",slug:"phenolic-compounds-with-anti-virulence-properties",totalDownloads:2388,totalCrossrefCites:11,totalDimensionsCites:18,hasAltmetrics:0,abstract:"Natural products represent the major source of approved drugs and still play an important role in supplying chemical diversity as well as new structures for designing more efficient antimicrobials. They are also the basis for the discovery of new mechanisms of antibacterial action. In this regard, a large number of substances, mainly extracts from natural sources, have been obtained in order to identify their anti-virulence activity. In recent years, there is an increase in the study of anti-virulence natural product derivatives. Different targets have been proposed as a solution to the serious problem of bacterial antibiotic resistance. Inhibition of bacterial quorum-sensing systems has been one of the most studied; however, there are other mechanisms involved in virulence regulation, damage to the host and bacterial survival, which suggests that there are another good targets such as bacterial secretion systems, biofilm formation, two-component systems, flagellum, fimbriae, toxins and key enzymes. Within the natural products, the main anti-virulence compounds are phenolic in nature, so that the next chapter describes and analyzes the relationship between chemical structure and activity of the main phenolic compounds reported.",signatures:"Naybi Muñoz-Cazares, Rodolfo García-Contreras, Macrina Pérez-\nLópez and Israel Castillo-Juárez",downloadPdfUrl:"/chapter/pdf-download/53180",previewPdfUrl:"/chapter/pdf-preview/53180",authors:[{id:"193519",title:"Dr.",name:"Castillo",surname:"Juárez",slug:"castillo-juarez",fullName:"Castillo Juárez"},{id:"193520",title:"Dr.",name:"García",surname:"Contreras Rodolfo",slug:"garcia-contreras-rodolfo",fullName:"García Contreras Rodolfo"},{id:"193521",title:"MSc.",name:"Pérez",surname:"López Macrina",slug:"perez-lopez-macrina",fullName:"Pérez López Macrina"},{id:"193522",title:"MSc.",name:"Muñoz",surname:"Cazares Naybi",slug:"munoz-cazares-naybi",fullName:"Muñoz Cazares Naybi"},{id:"197805",title:"Dr.",name:"Israel",surname:"Castillo Juárez",slug:"israel-castillo-juarez",fullName:"Israel Castillo Juárez"}],corrections:null},{id:"52824",title:"Regulatory Mechanism of Skeletal Muscle Glucose Transport by Phenolic Acids",doi:"10.5772/65968",slug:"regulatory-mechanism-of-skeletal-muscle-glucose-transport-by-phenolic-acids",totalDownloads:2102,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Type 2 diabetes mellitus (T2DM) is one of the most severe public health problems in the world. In recent years, evidences show a commonness of utilization of alternative medicines such as phytomedicine for the treatment of T2DM. Phenolic acids are the most common compounds in non-flavonoid group of phenolic compounds and have been suggested to have a potential to lower the risk of T2DM. Skeletal muscle is the major organ that contributes to the pathophysiology of T2DM. Studies have shown that several phenolic acids (caffeic acid, chlorogenic acid, gallic acid, salicylic acid, p-coumaric acid, ferulic acid, sinapic acid) have antidiabetic effects, and these compounds have been implicated in the regulation of skeletal muscle glucose metabolism, especially glucose transport. Glucose transport is a major regulatory step for whole-body glucose disposal, and the glucose transport processes are regulated mainly through two different systems: insulin-dependent and insulin-independent mechanism. In this chapter, we reviewed recent experimental evidences linking phenolic acids to glucose metabolism focusing on insulin-dependent and insulin-independent glucose transport systems and the upstream signaling events in skeletal muscle.",signatures:"Tatsuro Egawa, Satoshi Tsuda, Rieko Oshima, Ayumi Goto, Xiao Ma,\nKatsumasa Goto and Tatsuya Hayashi",downloadPdfUrl:"/chapter/pdf-download/52824",previewPdfUrl:"/chapter/pdf-preview/52824",authors:[{id:"193107",title:"Dr.",name:"Tatsuro",surname:"Egawa",slug:"tatsuro-egawa",fullName:"Tatsuro Egawa"},{id:"193126",title:"MSc.",name:"Satoshi",surname:"Tsuda",slug:"satoshi-tsuda",fullName:"Satoshi Tsuda"},{id:"193127",title:"Prof.",name:"Katsumasa",surname:"Goto",slug:"katsumasa-goto",fullName:"Katsumasa Goto"},{id:"193128",title:"Prof.",name:"Tatsuya",surname:"Hayashi",slug:"tatsuya-hayashi",fullName:"Tatsuya Hayashi"},{id:"195578",title:"Dr.",name:"Rieko",surname:"Oshima",slug:"rieko-oshima",fullName:"Rieko Oshima"},{id:"195646",title:"Dr.",name:"Ayumi",surname:"Goto",slug:"ayumi-goto",fullName:"Ayumi Goto"},{id:"195708",title:"Prof.",name:"Xiao",surname:"Ma",slug:"xiao-ma",fullName:"Xiao Ma"}],corrections:null},{id:"54035",title:"Health Benefits of Phenolic Compounds Against Cancers",doi:"10.5772/67232",slug:"health-benefits-of-phenolic-compounds-against-cancers",totalDownloads:2965,totalCrossrefCites:11,totalDimensionsCites:34,hasAltmetrics:1,abstract:"Phenolic compounds are the biggest group of phytochemicals, and many of them have been found in plant‐based foods. Polyphenol‐rich diets have been linked to many health benefits including cancer. The potential anti‐carcinogenic mechanisms of action that have been so far identified for phenolic compounds, as well as the feasibility reports occurred in vivo. In general terms, under the oxidative stress, polyphenols could act in those cellular mechanisms by participating in the modulation of the redox status and on multiple key elements in intracellular signal transduction pathways related to cell proliferation, differentiation, apoptosis, inflammation, angiogenesis and metastasis. A protective role of polyphenols against carcinogenesis is supported by many studies carried out on animal models and different mechanisms of action have been proposed to explain such protective effects. Studies performed in animals have demonstrated that phenolic components can prevent and/or slow down the initiation‐progression of different types of cancers. They act through the regulation of cell signal transduction and gene expression and exhibit either up or down regulation of genes controlling tumor development.",signatures:"Abdelkader Basli, Nassim Belkacem and Iman Amrani",downloadPdfUrl:"/chapter/pdf-download/54035",previewPdfUrl:"/chapter/pdf-preview/54035",authors:[{id:"193750",title:"Dr.",name:"Basli",surname:"Abdelkader",slug:"basli-abdelkader",fullName:"Basli Abdelkader"},{id:"195990",title:"Mr.",name:"Belkacem",surname:"Nacim",slug:"belkacem-nacim",fullName:"Belkacem Nacim"},{id:"195991",title:"Dr.",name:"Amrani",surname:"Iman",slug:"amrani-iman",fullName:"Amrani Iman"}],corrections:null},{id:"53661",title:"Health Status Improved by Aronia Melanocarpa Polyphenolic Extract",doi:"10.5772/66882",slug:"health-status-improved-by-aronia-melanocarpa-polyphenolic-extract",totalDownloads:1781,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter focuses on certain natural polyphenolic extracts from Aronia melanocarpa (Michx.) Elliott and also on their effects in insulin-dependent diabetes mellitus. The phenolic profile of berries ethanolic extract was characterized by HPLC/DAD/ESI-MS. HPLC/DAD/ESI-MS allowed identification of five phenolic compounds: chlorogenic acid, kuromanin, rutin, hyperoside, and quercetin. The results reveal that the glycosylated hemoglobin values are much higher in the diabetic group (DM) and they are significantly lower in the group protected by polyphenols (DM+P). It is found that due to the polyphenolic protection of the rats from the DM+P, the atherogen risk is preserved at normal limits. The serous activity of glutathione-peroxidase (GSH-Px) and superoxide-dismutase (SOD) has significantly lower values in the diabetic group as compared to the group protected by polyphenols. Renal function indicators like creatinine and blood-urea nitrogen (BUN) were also elevated in the streptozotocin diabetic rats when compared with control rats. When compared with the diabetic group the elevated levels of BUN was significantly (p < 0.001) reduced in animals treated with natural polyphenols. Through the hypoglycemiant, hypolipemiant, and antioxidant effects, A. melanocarpa represents a possible dietary adjunct for the treatment of diabetes and a potential source of active agents for the prevention of microvascular diabetes complications.",signatures:"Manuela Ciocoiu, Laurentiu Badescu and Magda Badescu",downloadPdfUrl:"/chapter/pdf-download/53661",previewPdfUrl:"/chapter/pdf-preview/53661",authors:[{id:"193903",title:"Prof.",name:"Manuela",surname:"Ciocoiu",slug:"manuela-ciocoiu",fullName:"Manuela Ciocoiu"},{id:"195685",title:"Dr.",name:"Laurentiu",surname:"Badescu",slug:"laurentiu-badescu",fullName:"Laurentiu Badescu"},{id:"195686",title:"Prof.",name:"Magda",surname:"Badescu",slug:"magda-badescu",fullName:"Magda Badescu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6029",title:"Phenolic Compounds",subtitle:"Natural Sources, Importance and Applications",isOpenForSubmission:!1,hash:"348060e7a0fee08ee1feb9d82b330ec3",slug:"phenolic-compounds-natural-sources-importance-and-applications",bookSignature:"Marcos Soto-Hernandez, Mariana Palma-Tenango and Maria del Rosario Garcia-Mateos",coverURL:"https://cdn.intechopen.com/books/images_new/6029.jpg",editedByType:"Edited by",editors:[{id:"65790",title:"Prof.",name:"Marcos",surname:"Soto-Hernández",slug:"marcos-soto-hernandez",fullName:"Marcos Soto-Hernández"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7688",title:"Plant Physiological Aspects of Phenolic Compounds",subtitle:null,isOpenForSubmission:!1,hash:"16f7407afbf69173f4fa419b4338a6c8",slug:"plant-physiological-aspects-of-phenolic-compounds",bookSignature:"Marcos Soto-Hernández, Rosario García-Mateos and Mariana Palma-Tenango",coverURL:"https://cdn.intechopen.com/books/images_new/7688.jpg",editedByType:"Edited by",editors:[{id:"65790",title:"Prof.",name:"Marcos",surname:"Soto-Hernández",slug:"marcos-soto-hernandez",fullName:"Marcos Soto-Hernández"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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It should provide researchers with the necessary material to understand and evaluate spontaneous propagation of lipid monolayers [2, 3] and double bilayers [2, 4] on solid supports, which occurs when lipid reservoirs are brought in contact with low- and high-energy surfaces, respectively, in an aqueous environment. The first section provides a brief introduction of surfaces and interfaces, the second section is dedicated to the mechanism of interaction of lipid films with the supporting surface during wetting, and the third section introduces the formation of ruptures in double bilayers caused by that interaction.
Biological membranes organize cellular complexity, and thus establish and promote structure in the living world [5]. They compartmentalize the cell, form transport networks, organize proteins, serve as a smart barrier for molecules and ions, and establish the chemical identity of the cell. The fundamental structure of the cellular membrane is the phospholipid bilayer, consisting of a large number of individual phospholipid molecules, which organize themselves spontaneously in a self-assembly process. The membrane has peculiar characteristics, is highly dynamic, and features two-dimensional fluidity [6]. It can accommodate proteins and other functional molecules which fulfil important functions such as recognition, signal transduction, and transport of chemical entities through the membrane.
Biomembrane models, designed to capture some of the features of the cell membrane in a simplified setting, have become a popular research subject [7, 8]. They are naturally less complex than their biological counterpart, but can be relatively easily assembled, for example, on suitable flat solid surfaces (supported membranes), or as spherical membrane compartments, often referred to as vesicles or liposomes [9]. In the past few decades, a large number of model systems of increasing sophistication have been introduced, often with the purpose to identify and study the role and function of lipids and other membrane components in the cell [7, 10]. In particular, the two-dimensional fluidity of the membrane and their ability to harbour proteins have been in the centre of attention.
Although self-organization of lipid molecules to lipid membranes occurs spontaneously, which is frequently exploited to assemble membranes from lipid mixtures in solution in experimental settings, controlled assembly and preparation of stable, well-defined phospholipid films on supporting surfaces, such as glass, metals and metal oxides, are still challenging engineering tasks.
The deposition of lipid reservoirs onto various solid surfaces leads to formation of self-spreading surface-supported lipid films [1, 11]. Lipid reservoirs range from manually deposited single sources (multilamellar liposomes) to liposome suspensions of different particle sizes [10, 12], which can be directly transferred onto the substrate, either manually with glass microneedles [13] or by means of sophisticated microfluidic instrumentation [10, 14]. The following chapter is dedicated to the formation of lipid mono- and bilayer membranes by means of self-spreading from a lipid source. The result of lipid spreading is typically a solid-supported self-assembled membrane, i.e., a continuous supramolecular structure with two-dimensional fluidity. Each of the three forms of supported membranes mentioned above represents a real biological structure. Monolayers surround lipid droplets in cells, which are small stocks of lipid molecules regulating lipid metabolism of the cell [15]. Single bilayers are – in terms of composition – simplified versions of the plasma membrane of cells, which resides on top of the cytoskeleton. Spreading double bilayers are reminiscent of spreading cell membranes, which in addition to a lipid membrane contain actin filaments [16]. Accordingly, each of the supported membrane types can be utilized in experimental studies to address different questions. The supported bilayer is the most commonly used model system, as it directly resembles the membrane of the biological cell. Supported bilayer structures can be easily prepared in an aqueous environment on available surfaces that are compatible with microscopy experiments, such as glass, mica, or sapphire plates. Nowadays, with microfabrication and micromanipulation equipment being commonplace, a greater variety of surfaces is available, for example, silicon or aluminium oxide coated glass, which opened pathways for the generation of self-spreading double bilayers from lipid reservoirs. In particular, amorphous fluoropolymers and the epoxy photoresist SU-8, which can be utilized to coat and pattern a variety of surfaces with nanoscopic polymer films [17, 18], have enabled experiments where single reservoirs are manually deposited, allowing for the controlled generation of self-spreading lipid monolayers. Table 1 gives an overview over the most relevant publications [19 - 54] in the area of lipid film research from 1985 to present. It covers fabrication, biophysical characterization, and utilization in, for example, membrane protein studies.
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tDe Gennes, P.G. | \n\t\t\tRev. Modern Phys. | \n\t\t\t1985 | \n\t\t\t[19] | \n\t\t\tOne of the first articles in wetting of liquids on solid substrates, cited 3700 times | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tEvans E. And Sackmann S. | \n\t\t\tJournal of Fluid Mechanics | \n\t\t\t1988 | \n\t\t\t[20] | \n\t\t\tFirst theoretical framework of spreading/wetting membranes and relation to friction (drag) coefficient; supports the current model explained throughout the chapter. | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tRädler J. | \n\t\t\tLangmuir | \n\t\t\t1995 | \n\t\t\t[2] | \n\t\t\tPioneer study, kinetics of lipid wetting via self-spreading lipid reservoirs: bilayer, double bilayer membranes | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tSackmann, E. | \n\t\t\tScience | \n\t\t\t1996 | \n\t\t\t[8] | \n\t\t\tFirst examples of polymer cushioned protein incorporated bilayers, double bilayers, supported lipid bilayer-based biosensors | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tKochev V. And Karabaliev M. | \n\t\t\tAdvances in Colloid and Interface Science | \n\t\t\t2004 | \n\t\t\t[21] | \n\t\t\tReview of basic principles underlying the techniques of formation, as well as the conditions of the films stability. | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tSuzuki K. and Masuhara H. | \n\t\t\tLangmuir | \n\t\t\t2005 | \n\t\t\t[22] | \n\t\t\tMultilayer self-spreading lipid bilayers | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tBorghi N. | \n\t\t\tJ. of Colloid and Interface Sci. | \n\t\t\t2005 | \n\t\t\t[23] | \n\t\t\tCoating fibers with lipids through lipid wetting | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tRichter R.P. | \n\t\t\tBiophysical Journal | \n\t\t\t2005 | \n\t\t\t[24] | \n\t\t\tStudy of bilayer formation dynamics by a combination approach of different analytical surface techniques | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tRichter R.P. | \n\t\t\tBiophysical Journal | \n\t\t\t2005 | \n\t\t\t[25] | \n\t\t\tSupported membrane protein studies | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tRichter R.P. | \n\t\t\tLangmuir | \n\t\t\t2006 | \n\t\t\t[26] | \n\t\t\tStudy of bilayer formation dynamics | \n\t\t
\n\t\t\t\t | \n\t\t\tSupported lipid bilayer self-spreading on a nanostructured silicon surface. | \n\t\t\tFurukawa K. | \n\t\t\tLangmuir | \n\t\t\t2006 | \n\t\t\t[27] | \n\t\t\tSelf-spreading in combination with nanostructured surfaces | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tErkan Y. | \n\t\t\tLangmuir | \n\t\t\t2007 | \n\t\t\t[28] | \n\t\t\tLipid monolayer self-spreading/wetting | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tCzolkos I. | \n\t\t\tNano Letters | \n\t\t\t2007 | \n\t\t\t[3] | \n\t\t\tLipid monolayer self-spreading/wetting | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tZhou X. | \n\t\t\tNature Comm. | \n\t\t\t2007 | \n\t\t\t[29] | \n\t\t\tLipid wetting over single-walled carbon nanotube transistors | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tVan Meer G. i | \n\t\t\tNature Rev. Mol. Cell Biol. | \n\t\t\t2008 | \n\t\t\t[30] | \n\t\t\tReview on plasma membrane lipids: structure, phase behavior, function | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tGauthier N.C. | \n\t\t\tMol. Biology of the Cell | \n\t\t\t2009 | \n\t\t\t[31] | \n\t\t\tCell membrane spreading similar to double lipid bilayer spreading | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tLobovkina T. | \n\t\t\tSoft Matter | \n\t\t\t2010 | \n\t\t\t[11] | \n\t\t\tDouble lipid bilayer self-spreading/localized Marangoni flow | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tGözen I. et al. | \n\t\t\tNature Materials | \n\t\t\t2010 | \n\t\t\t[4] | \n\t\t\tDouble lipid bilayer self-spreading, wetting through rupturing | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tCho N.J. | \n\t\t\tNature Protocols | \n\t\t\t2010 | \n\t\t\t[32] | \n\t\t\tQCM-D as a measure of wetting of solid surfaces by lipid bilayers | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tGołabek M., Hołysz L. | \n\t\t\tApplied Surface Science | \n\t\t\t2010 | \n\t\t\t[33] | \n\t\t\tInvestigation of wetting and energetic properties of different lipid layers deposited on the glass surface, carried out by contact angles measurements and determination of the apparent surface free energy . | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tHan X. | \n\t\t\tChemPhysChem | \n\t\t\t2010 | \n\t\t\t[34] | \n\t\t\tBilayer on bilayer formation using fusogenic reagents | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tIsono T., Ikeda T., and Ogino T. | \n\t\t\tLangmuir | \n\t\t\t2010 | \n\t\t\t[35] | \n\t\t\tSupported bilayer wetting on varying topology | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tOliver A.E. and Parikh A.N. | \n\t\t\tBiochim. Biophys. Acta - Biomembranes | \n\t\t\t2010 | \n\t\t\t[36] | \n\t\t\tMonolayer/bilayer/interfaces | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tGözen I. | \n\t\t\tSoft Matter | \n\t\t\t2011 | \n\t\t\t[37] | \n\t\t\tLipid wetting is tuned with Ca2+ ions, leading to tubulation | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tNabika H. | \n\t\t\tPhys. Chem. Chem. Phys. | \n\t\t\t2011 | \n\t\t\t[38] | \n\t\t\tSelf-spreading bilayers on nanostructures | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t \n\t\t\t\t | \n\t\t\tNair P.M. | \n\t\t\tNature Protocols | \n\t\t\t2011 | \n\t\t\t[39] | \n\t\t\tProtocol supported bilayer, SUV rupture | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tMohamad, S. | \n\t\t\tPhysical Review Letters | \n\t\t\t2012 | \n\t\t\t[40] | \n\t\t\tInvolves surface-enhanced ellipsometric contrast microscopy to observe the spreading of egg phosphatidylcholine nanodroplets on a hydrophilic substrate | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tGözen I. and Jesorka A. | \n\t\t\tAnalytical Chemistry | \n\t\t\t2012 | \n\t\t\t[41] | \n\t\t\tReview on characterization methods and tools for surface-supported membranes | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tGozen I. | \n\t\t\tSoft Matter | \n\t\t\t2012 | \n\t\t\t[42] | \n\t\t\tWetting of proximal bilayers via rupturing of distal bilayers | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t \n\t\t\t\t | \n\t\t\tGauthier N.C. | \n\t\t\tTrends in Cell Biology | \n\t\t\t2012 | \n\t\t\t[43] | \n\t\t\tCell spreading | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tSubramaniam A.B. | \n\t\t\tNature Materials | \n\t\t\t2013 | \n\t\t\t[44] | \n\t\t\tHow self-spreading model membranes can be used to understand membrane-mediated transport processes. Findings indicate an intimate coupling between cellular lipidomes and glycomes. | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t \n\t\t\t\t | \n\t\t\tHirtz M. | \n\t\t\tNature Comm. | \n\t\t\t2013 | \n\t\t\t[45] | \n\t\t\tLipid bi-/multilayer wetting using dip-pen lithography | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tGözen I. | \n\t\t\tSoft Matter | \n\t\t\t2013 | \n\t\t\t[46] | \n\t\t\tDifferent cause of bilayer-on-bilayer wetting | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tPietuch A., and Janshoff A. | \n\t\t\tOpen Biology | \n\t\t\t2013 | \n\t\t\t[47] | \n\t\t\tCell spreading | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tAinla A. | \n\t\t\tScientific Reports | \n\t\t\t2013 | \n\t\t\t[10] | \n\t\t\tPrinted/spreading bilayers deposited by a microfluidic pipette | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t \n\t\t\t\t | \n\t\t\tNguyen P.A. | \n\t\t\tScience | \n\t\t\t2014 | \n\t\t\t[48] | \n\t\t\tSupported bilayers used to study the effect of (artificial) centrosomes, an application example | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tMotegi T. | \n\t\t\tLangmuir | \n\t\t\t2014 | \n\t\t\t[49] | \n\t\t\tNanofabricated obstacle-based molecular filtering of self-spreading lipid bilayer membrane | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t \n\t\t\t\t | \n\t\t\tWatanabe R. | \n\t\t\tNature Comm. | \n\t\t\t2014 | \n\t\t\t[50] | \n\t\t\tLipid wetting from a lipid reservoir, this time not onion-like but dissolved lipids in solvent used for single-molecule studies | \n\t\t
\n\t\t\t\t | \n\t\t\tSolvent-assisted lipid bilayer formation on silicon dioxide and gold | \n\t\t\tTabaei S. | \n\t\t\tLangmuir | \n\t\t\t2014 | \n\t\t\t[51] | \n\t\t\tImpact of solvent in membrane wetting type | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tShaali M. e | \n\t\t\tACS Nano | \n\t\t\t2015 | \n\t\t\t[52] | \n\t\t\tPrecise patterning of self-spreading monolayers using E-beam lithography | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\tMa L. | \n\t\t\tCell Research | \n\t\t\t2015 | \n\t\t\t[53] | \n\t\t\tPlasma membrane dewetting on solid support during cell migration | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t \n\t\t\t\t | \n\t\t\tWu, I.-L. | \n\t\t\tNature Comm. | \n\t\t\t2015 | \n\t\t\t[[54]] | \n\t\t\tSolid support as micron-size silica beads (spherical) instead of flat surfaces | \n\t\t
Selected publications in the field of lipid self-spreading/wetting
Supported lipid membranes form on solid surfaces, where many of the membrane properties are depending on the properties of the underlying surface, including material and composition, surface charge, roughness, and surface tension. The wetting phenomena observed in double bilayers only occur on solid high-energy surfaces, such as silicon oxide, or aluminium oxide films. In contrast, the wetting phenomena leading to lipid monolayers occur exclusively on low-energy hydrophobic polymer surfaces. The surface tension is a central concept, that is, in principle, a measure of how much energy is associated with a surface per unit area. If in a thought experiment a cube with the side length
High-energy surfaces (
In water (and likewise in other monomolecular fluids), the molecules in the bulk are surrounded by other water molecules, where they are energetically indistinguishable. Only at solid and gas interfaces (e.g., the walls of a container, or the water vapour/water interface in an open container), there are molecules which experience different forces. The resulting energetic differences with respect to the bulk molecules are reflected by the interfacial tension of the solid–liquid interface
Hydrophobic (or high-energy) surfaces feature small contact angles of
In addition, the roughness of a surface is of considerable importance to its wetting properties, which was discovered by Wenzel in 1936 [59]. In nature, topographical surfaces with regular or irregular features on the micro- or nanoscale have a water-repelling function. The most prominent examples are the leaves of the Sacred Lotus, which has a nanopatterned surface to protect it from water, and the skin of sharks, which give the animal the ability to move faster in water. These superhydrophobic surface features, which are characterized by very large contact angels of
A lipid reservoir brought into contact with a solid substrate leads to wetting of the surface by lipids in the form of a molecularly thin phospholipid film. Lipid reservoirs can be considered as stocks of phospholipid molecules and can exist in various forms. Rädler et al. have used “solid lipid sources” as reservoirs, which they have described as irregularly wrapped (entangled) layers of lipid bilayers [2]. The reservoirs have been referred to as “lipid lumps” in a few other studies and illustrated as liquid drops in which the individual lipid molecules are randomly oriented [22]. Multilamellar vesicles (MLVs) containing several hundreds of lipid bilayers packed in a compact sphere can also be employed as lipid reservoirs [4, 11]. Because of their dense, layered structure, such vesicles are also referred to as “onion shell vesicles” [61]. The internal molecular structure of such lipid reservoirs can be complex and the mechanisms of initiation of wetting from such reservoirs have not yet been fully understood. We will further comment on the potential impact of the lipid reservoir structure on wetting dynamics in the later paragraphs of this chapter.
Due to wetting, individual lipids originating from a lipid source self-assemble on a solid surface as a planar lipid film, extending the surface area over a distance of several tens to hundreds of microns. The wetting motion of lipids on solid substrates is therefore commonly referred to as “lipid spreading”. Since the spreading is generally not initiated due to an external stimulus, but begins rather spontaneously, ensuring energetically the most favourable conditions, the spreading is further defined as “lipid self-spreading”.
In context of this chapter, lipid wetting of a solid substrate occurs in biologically relevant conditions, e.g., in water-based physiological buffers. Let us consider the spreading of a lipid monolayer. When a lipid source is deposited on a hydrophobic substrate in the presence of an aqueous solution, surface tension at two interfaces may play a role in wetting. One is the tension at interface of lipids with the solid substrate (
Structure of the wetting lipid film depends on the nature of the solid surface, e.g., if it is of high or low energy, a hydrophilic or hydrophobic substrate. Single bilayers tend to form on moderately hydrophilic substrates such as glass. Double bilayer wetting can be observed on silicon oxides and multiple metal oxide surfaces which are generally considered to be high-energy substrates. On hydrophobic surfaces like fluoropolymers or the epoxy SU-8, lipids spread as monolayers, i.e., as a single leaflet of a lipid bilayer. This can be expected since the hydrocarbon chains of lipid molecules would tend to face towards the hydrophobic surface.
The mechanism of interaction with the surface during wetting varies, depending on the nature of the substrate. The monolayer lipids form due to the hydrophobic interactions with the surface. Spreading monolayers screen along the buffer–surface interface, establishing a direct contact with the hydrophobic substrate (Figure 1a). During single bilayer spreading on glass or mica, there remains a thin (few nm) lubricating layer beneath the membrane (Figure 1b). The bilayers spread by “sliding” on top of the water layer. The interaction between the bilayer and the surface is governed by hydration and the van der Waals forces. Double bilayer spreading on highly oxidized silica or other metals is mostly under the influence of electrostatic interactions. Physiological buffers have high ionic strength and contain multivalent ions, for example, Ca2+ or Mg2+. These positively charged entities in the ambient solution act as “fusogenic agents” and establish bridging connections between the negatively charged phospholipid headgroups and the negatively charged surface (Figure 1c). This facilitates the spreading of lipid films on oxidized surfaces. Concentrations of only a few mM/L [62] of divalent cations and 10–5 M of trivalent cations have a dramatic effect on surface potentials. For instance, they can neutralize a negatively charged surface and even start to accumulate positive charges [62]. A few studies have reported on multi-bilayer spreading featuring up to seven bilayers on Si/SiO2 surfaces [22, 63], but very little is known about the spreading dynamics.
Self-spreading of multilamellar vesicles on solid substrates leads to circular lipid patches (Figure 1d). The main reason for the circular geometry lies in the spreading dynamics which is characterized by Darcy flow. Briefly, the spreading front can be described by the same equation that is used to describe a Saffman-Taylor instability (a specific form of Darcy flow), but with the opposite sign. Therefore, any perturbation from a circular shape during spreading will be rapidly damped. We will explain thoroughly why membrane flow is a form of Darcy flow in the next section.
The overall tension (
Lipid self-spreading. Illustrations showing in a side view the cross-sectional edge profiles of a spreading (a) monolayer, (b) single bilayer, and (c) double bilayer. The spreading monolayer is directly in contact with the substrate. The single bilayer exhibits sliding motion on a thin lubricating water layer. During double bilayer spreading, positively charged ions bridge the proximal (lower) bilayer to the surface, where the distal (upper) bilayer slides on a layer of water trapped in between the two layers.
Lipid self-spreading is therefore considered to be a form of
The lipid reservoir has also an internal tension (
Note that the terms in Eq. (3) and (4) may not fully represent the single and the double bilayers. As described above, during monolayer spreading the lipids replace the water molecules on the surface; therefore, terms
Different wetting modes of phospholipids can be distinguished by a kinetic spreading coefficient,
The spreading power (
Next, we will formulate the spreading coefficients for different modes of lipid self-spreading on solid supports. These modes include monolayers, single bilayers, and double bilayers. We will first adapt a one-dimensional model which had been originally proposed by Rädler et al. for single lipid bilayer spreading [2].
We make two main assumptions to establish our model, which would be valid for all three types of lipid spreading:
membrane flow can be described by a two-dimensional Stokes equation:
where
This means that the tension gradient (
To a first degree of approximation, lipid membranes are incompressible [20].
Combining Eq. (8) and (9) leads to:
Combining Eq. (10) and (11) leads to:
This means that the membrane flow caused by the tension difference over a radius R is dissipated by the friction. The velocity at the spreading edge of a double bilayer (
The membrane velocity with respect to the velocity at the spreading edge at a distance R from the center is:
Eq. (12a) and (12b) can be inserted into Eq. (12), which leads to:
During spreading, the radius of the circular lipid patch would grow from
The radius of the spread at
The derivative of
As mentioned above, the spreading power
Inserting Eq. (6) into Eq. (16a) and (16b) will provide the spreading coefficient
After determining the spreading coefficient with regards to membrane velocity by adapting a one-dimensional model, we will now determine the relationships for a two-dimensional model. The two-dimensional model would provide more insights for lipid self-spreading in correlation with experiments, since the two-dimensional wetting of a lipid membrane can be monitored experimentally, for example, via confocal microscopy (Figure 1d). In such experiments, a self-spreading membrane doped with a membrane-attached fluorophore can be observed from top view as a circular patch with quite a distinct circumference (Figure 1d). On this circular patch, we imagine an arbitrary ring with an inner radius
The lipid molecules coming from the reservoir will pass through
where
We will initiate the formulation of our two-dimensional model by rearranging Eq. (19):
The velocity of the spreading edge of the double bilayer membrane is again half the velocity of the membrane (
Inserting Eq. (19a) and (19b) into Eq. (8) gives:
Integrating Equations (20a) and (20b) from
The spreading power (
By monitoring the self-spreading of a fluorescently labelled monolayer on a SU-8 surface over time under a microscope,
Rädler et al. have reported the experimental values of
The friction coefficient, which characterizes the lower monolayer leaflet of the distal bilayer and the upper monolayer leaflet of the proximal bilayer during bilayer rolling (double bilayer spreading), has been experimentally determined to be
In the previous sub-chapter, we described the details of the spreading motion of lipids on solid supports in various forms, without reporting on the eventual outcome of such spreading. Spreading continues until the reservoir is depleted, or exhausted due to defects. This will cause termination of lipid supply from the source to the spreading membrane, so that the spreading motion will slow down and eventually almost stop. In the meantime, the adhesion energy remains constant. This means that regardless of the insufficient lipid supply, the spreading edge of the membrane will favour lipid wetting and tend towards adhering. Note that a lipid membrane cannot stretch more than 5% of its surface area [67]. The fate of the spreading from this point on will differ depending on the type of the surface and corresponding spreading mode.
When the reservoir is completely consumed and the spreading velocity reaches zero, the circumference of a spreading monolayer starts to “evaporate” [68]. Evaporation occurs when the hydrophobic tails of individual lipids lay open and completely adhere to the substrate. If the membrane is tagged with fluorophores, the evaporating rim of the membrane can be observed as a fuzzy edge rather than a distinct one. The driving force for the evaporation of monolayers is the increase in entropy which in turn minimizes the Gibbs free energy.
Similarly, single bilayer spreading simply comes to an end when the reservoir is depleted. It has recently been shown that an additional stock of lipids can be provided to a supported bilayer lacking a reservoir, by using a microfluidic pipette device for continuous supply [10]. Briefly, at the tip of the microfluidic pipette, a virtual flow cell provides a steady hydrodynamically confined flow, featuring a low Reynolds (Re) and a high Péclet (Pe) number. This flow cell can therefore deliver liquid cargo locally to a surface under highly controlled laminar flow conditions. By using the microfluidic pipette, it is possible to supply and fuse small unilamellar lipid reservoirs (vesicles
For a double bilayer membrane, the free energy can further be minimized, if the distal bilayer ruptures and adheres on the substrate. Rupturing of the distal membrane is possible if the tension of the membrane increases due to the continuous adhesion of the membrane edge to the substrate, and exceeds the lysis tension. In 2010, two forms of ruptures occurring in the distal bilayer of spreading double bilayer membranes have been reported. The “floral” ruptures, named after pore morphologies resembling flowers, can be observed mostly at the centre of a circular lipid spread propagating towards its periphery (Figure 2a). Such pores continuously grow until the double bilayer membrane entirely transforms into a single bilayer membrane on the solid support. The second rupture type appears in “fractal” patterns, most frequently at the circumference of the lipid patch, and develops inwards in the form of avalanches (Figure 2b). Within the fractal ruptures there remain “islands”, the entrapped regions of the distal membrane which are strongly pinned to the proximal bilayer. Except for the islands, the lipid material of the upper bilayer migrates towards the edges (cf. Figure 1c) and is deposited on the surface in the same manner as during floral rupturing. Since the fractal ruptures propagate in form of avalanches, the wetted area on the surface increases step-wise over time. Both types of rupture formation are spontaneous, and occur when the lipid reservoir is exhausted. Discrimination among the two rupture types has been attributed to the amount of pinning between the two bilayers. The pinning can be established by means of Ca2+ or other multivalent cations present in the ambient buffer. A high number of pinning sites is assumed to favour fractal morphology. Precise control of the number and location of pinning sites during spreading/rupture experiments has not yet been achieved.
We want to dedicate this sub-chapter to membrane ruptures, as the displacement of the membrane on the surface during rupturing is a form of wetting of the solid substrate, and also a simultaneous form of de-wetting of the proximal bilayer membrane (Figure 2c). Next, we will describe a mathematical analogy between the dynamics of floral ruptures and the dynamics of flow in conventional “porous media”. A porous medium can be depicted as a fluidic compartment packed regularly with particles, for example, micron-size beads. Such fluidic media can consist of, for example, glycerol, oil, or water. If now a secondary fluid of lower viscosity is pushed through the porous medium to displace the existing fluid, a morphologically instable interface between the two immiscible fluids is formed. Common injection fluids in flow experiments in porous media are water and air. Water can be injected only into liquids with higher viscosity, e.g., glycerol, but is often used as the main medium itself, if the injected fluid is air. The instability at the boundary of two immiscible fluids formed during the flow in a porous medium exhibits complex, finger-like patterns, therefore, is referred to as “viscous fingering” [69]. Membrane ruptures highly resemble these fingering instabilities. A membrane flow causing edge instabilities is comprehensible since the lipid membranes are considered as two-dimensional fluids. One interesting aspect regarding the similarities between the viscous fingering and the membrane pore edge instabilities is the difference in length scales: membrane ruptures are of micrometer size where fingering patterns is in the order of centimetres.
Viscous fingering instabilities can be observed in a “Hele-Shaw cell”, which is an experimental set up explicitly designed to simulate the flow in a three-dimensional porous media in a two-dimensional environment. The cell consists of two flat glass plates, positioned in parallel and separated with an infinitesimally small distance
Eq. (7), which describes the membrane flow (
where
The inviscid edge at the moving boundary of the fluids is balanced by the pressure of the invading liquid:
where
where
The instability of a membrane pore edge, where the pore void represents an inviscid fluid, is mathematically analogous to a Saffman-Taylor instability [69]. A periodic membrane edge modulation can be expressed as
Here,
In a basic Hele-Shaw cell the porosity is regular. An inhomogeneous porosity can be introduced into the cell by placing grains, e.g., glass beads at random locations. This leads to irregular permeability where the capillary forces become significantly effective and eventually cause fractal displacements termed invasion percolation clusters. The percolation clusters form when invading fluid chooses the “path of least resistance”, entrapping islands of the displaced fluid. This can be achieved, for example, by injecting air into water. The displacements appear in characteristic bursts with a broad size distribution, known as Haines jumps, which are similar to the avalanches observed during fracturing of the lipid membranes. The islands within the clusters are comparable to the islands surrounded by the fractal ruptures. Another similarity is the fractal dimension (
A Hele-Shaw cell contains particles or beads which provide the effect of porosity. In between the proximal and the distal membranes, there are no particles, but a corresponding effect is established by “pinning”. The pinning can be due to the Ca2+ ions which bridge bits of the two bilayers together [71]. The pinned regions become visible during formation of floral ruptures in forms of thin threads at the pore edges [4]. The pinning points, where the fluidity is reduced, act like solid particles and play the role of grains in a Hele-Shaw cell. One other reason for pinning can be the surface structure. Nanometer-sized grains of silicon dioxide (SiO2) are known to create incisions in solid-supported lipid membranes. The granules of surface therefore can punch through the proximal bilayer and act like particles placed in between the two bilayers. The flow of lipids during rupturing is therefore considered to be through a porous medium.
A clearly defined analogy between the fractal ruptures and the invasion percolation instabilities, as we have previously shown for the floral ruptures and the Saffman-Taylor instabilities, has not yet been established. However, it is possible to estimate a characteristic length scale for membrane pores, within which they are not expected to exhibit instabilities.
Free standing membranes produce circular pores with straight edges [72]. An instable pore edge in such a membrane can be pictured as a wave or a modulation. The excess energy of an instability compared to a straight edge (
Balancing the excess edge energy with dissipation (
In a supported membrane,
Balancing the dissipation and the excess energy of the instability gives:
A rupture propagating at velocity
For modulations larger than
Biological cells can also spread their membrane material on solid supports, often in order to be able to migrate. In some instances, a 200-nm thick lamellipodial sheet protrudes from the cell body onto the substrate. [73] The sheet includes a double layer of plasma membrane in addition to actin filaments sandwiched in between the layers. The detailed mechanism of cellular wetting is a subject still under debate. Whether the proceeding edge is rolling or sliding driven by actin polymerization is not yet known. The lamellipodia-based cellular wetting, however, have been found to follow a similar power law as discussed in Section 1.3. [73] Spreading of cells can also be promoted by introducing trivalent ions to the substrate, for example, Eu3+ ions onto SiO2. [4] In such conditions, Chinese Hamster Ovary (CHO) cells continuously adhere onto the substrate. Interestingly, the adhesion leads to the formation of fractal ruptures [4] as well as the islands, in distal plasma membrane of spreading CHO cells. Upon rupturing, the wetted area on the substrate suddenly increases in a step-wise manner, similar to the fractal ruptures of the self-spreading double bilayers. The plasma membranes are connected to the underlying scaffolding layer (cytoskeleton) via linking molecules. The membrane flows around the linkers; the plasma membrane flow on cytoskeleton, therefore, can be considered as a two-dimensional porous media flow, i.e., Darcy flow. The tension causing the ruptures is still moderate and in the range of plasma membrane adhesion to the cytoskeleton, or membrane–membrane adhesion, suggesting that such ruptures can in fact occur in vivo.
Another form of lipid wetting on solid substrates involving ruptures is accommodated by inter-membrane “defects” or “fusion pores” (Figure 2d). The fusion pores are nanometer-sized circular conduits connecting two membranes in the shape of an hour-glass. The dimension of pores (
The double bilayer membranes mentioned above exhibiting floral or fractal ruptures consists of two bilayers which are intact, performing a rolling motion. In some occasions, the proximal and distal bilayers split along the circumference. After splitting, the proximal bilayer continues to wet the surface, which can be observed by increasing the wetted area on the substrate. The area of the distal bilayer membrane remains unchanged over the time period of a few minutes, followed by sudden decreases caused by instant avalanche ruptures. The decrease in the area of the distal bilayer simultaneously causes an increase in the wetted area by the proximal bilayer. This supports the notion of a physical connection among the two bilayers, through which the lipids are transferred. The outer border of the distal membrane does not expand along the peripheries upon rupturing, as occurs for the floral and fractal ruptures, indicating that the distal membrane is not dragged by the proximal membrane along the circumference. The stretching and eventual rupturing of the distal membrane can therefore be caused by the downwards lipid flow towards the proximal bilayer, most likely through narrow vertical channels. [42]
Defects among lipid membranes may have already formed during swelling of MLVs or form dynamically during spreading as a response to physical or chemical cues. We had briefly mentioned in Section 1.3 the defects existing in onion vesicles or MLVs. Since the lipid layers packed in the reservoir later spreads on the surface, these defects can be transferred to the supported membranes. Additionally, changes in membrane tension may cause instantaneous (
The dynamics of lipid transfer via a fusion pore can be characterized semi-quantitatively via a “dissipation” function. Our model consists of a circular proximal bilayer, a circular distal bilayer and as an initial assumption: a single fusion pore with a diameter of 10 nm connecting these two membranes. Lipids flow from distal to proximal bilayer through the 10 nm defect, driven by the continuous adhesion of proximal bilayer to the substrate (Figure 2d). In this flow, there would be two separate forms of energy loss (dissipation). The first one is friction. The friction applies to the region (1) in between the proximal bilayer and the surface, (2) in between two bilayers since distal bilayer is de-wetting the proximal bilayer. The second form of dissipation is due to the viscous flow around the fusion pore. The lipid flow is expected to be different in remote areas of the membrane compared to the proximity of the pore. This is because the pore is small and the surfactants flowing through the pore collide with each other more intensely than they would in distant areas. Next, we will quantify and compare these two types of dissipations. If the magnitudes are compatible in relevant time scales, we will conclude that a single pore of 10 nm is sufficient to accommodate such a flow in between the membranes. If viscous flow (Stokes flow) cause dissipation that is much stronger than the frictional, this will indicate that several pores are required.
This brings us back to Eq. (7), where the difference of frictional and viscous forces determines the tension gradient across the membrane. A characteristic length scale where the frictional forces are of the same order as the viscous forces can be obtained based on Eq. (7) as:
The friction coefficient is:
where
For two-dimensional incompressible flow of the membrane, Eq. (7) leads to the following dissipation function [20]:
The integral Eq. (33) converges rapidly when
The dissipation caused by the sliding friction is composed of two parts: The sliding between the two bilayers (
Biomembrane ruptures as a cause of wetting. Confocal fluorescence micrographs of (a) floral (b) fractal membrane ruptures (top view). The double bilayer membrane areas can be visualized as twice as intense as the single bilayer areas. Darker regions are the proximal membrane which is visible through the ruptures in the distal membrane. (c) Cross-sectional schematic view of a rupturing distal membrane, representing (a) or (b). (d) Cross-sectional schematic view of a fusion pore connecting proximal and distal bilayers.
One can think of opening of large area pores in distal membranes as the process of de-wetting of the proximal bilayer. It is possible to reverse de-wetting by treating the pores with chemical ‘repair’ agents. When pores open in the membrane, the multivalent ions in the ambient buffer such as Ca2+ can penetrate through the pore edges and eventually pin fractions of the upper and lower bilayers together. At this instant, chelators such as 1,2-bis (o-aminophenoxy)ethane-N,N,N\',N\'-tetraacetic acid (BAPTA) can be introduced to the ambient buffer to target and deplete the Ca2+ ions. The chelators can bind to Ca2+ with high affinity and remove them from the pore edges and from the surface. This in turn frees the pore edges and reduces the overall membrane tension. Eventually, the membrane ruptures heal due to the pore edge tension (
The large area pores can form at different locations in the distal membrane. A fraction of the ruptures appear towards the edges of the distal bilayer as we had described above (Figure 2 b,e). There, one side of the pore edge maintains a physical connection to the MLV through the distal bilayer. The sealing of pores becomes possible through “bilayer-on-bilayer sliding” from the reservoir towards the pore region. Alternatively, rupturing may occur around the MLV (Figure 2a,f). In this case, there remains no direct contact of the distal bilayer to the lipid reservoir. The re-location of lipids towards the pore area can only be through the proximal bilayer. The free positive surface charges in the areas which are not wetted by the lipid membrane are mostly removed by BAPTA. This means depletion of fusogenic agents and termination of spreading. On the other hand, the access into the confined region between the proximal bilayer and the surface is impeded and chelation of the ions in the region above surface and underneath the membrane is expected to take significantly longer time. The total wetted area of the membrane on the solid substrate therefore can remain constant over several hours, confirmed by the experimental analysis [42]. While the edges of the spreading patch is pinned, reverse bilayer rolling becomes unlikely and one can presume the monolayer sliding to be the dominant flow mechanism for repair of such pores (Figure 2f).
To calculate the dissipation (
The dissipation (
where
The radius of the proximal membrane
Now we will calculate the dissipation for the second scnerio, where the membrane flow towards the pore area is through the monolayer sliding. The monolayer sliding occurs between the two leaflets within a bilayer and will be opposed by friction. The friction coefficient (
Here, index I refers to the surface area of the proximal bilayer; index II of the distal bilayer.
where
Based on experimental values inserted into Eq. (39),
Research on model membranes has been conducted for decades, and the understanding of the dynamics of lipid films has reached advanced levels. However, enabled by the rapid advances in micro- and nano-technologies and analytical capabilities, new phenomena are frequently discovered, such as the occurrence of the fractal membrane ruptures in double bilayer membranes, which created a new, exciting link between solid materials and the biological soft matter world. The discovery of this rupture phenomenon was closely related to the spontaneous wetting of high-energy surfaces, which was experimentally established in a microenvironment under the microscope. This and the other wetting phenomena described in the previous sub-chapters are feature-rich and have possible implications not only for future technological advancements, such as membrane protein studies, cell migration, but also for very advanced applications such as chemistry confined to two dimension. The double bilayer, which was at the heart of these investigations, can be easily classified as a new membrane model, which adds to the mono-, bi-, and cushioned bilayers. One can perhaps also view it, on one hand, as a self-cushioning bilayer, but on the other hand, it is essentially a flat giant unilamellar vesicle, with an approximately 10 nm thin water layer encapsulated between the two bilayer sheets. The thus encapsulated volume is on the order of a few hundred femtoliters. It bears a richness in possibilities for application in nanofluidics and artificial cell models, and potentially allows through its spreading an rupturing dynamics greater insights into, for example, the membrane-related mechanisms of cell migration and chemotaxis. We have provided in this chapter an overview over the wetting and rupturing properties and features of phospholipid monolayers and double bilayers on solid support, which should provide the foundation for the design of new experiments, and in many cases the prediction of their outcome. The dynamics of pores in membranes and associated materials transport phenomena, which are also accompanied with wetting phenomena, are also discussed. There are some particular points where further research is required. For example, attempts to establish a relationship for the spreading coefficient to quantitatively describe the spreading dynamics of double bilayers have so far been unsuccessful, which leaves the spreading approach to lipid film formation in this case still not entirely predictable.
The empirical approach to antimicrobial therapy among health care professionals and the concurrent patronage of over-the-counter antibiotics by patients have together caused an exponential rise in multidrug resistance among clinically relevant antimicrobials and with increasing trends for the past two decades [1]. Different mechanisms of antimicrobial resistance have been proposed, including the (i) alteration of the antibiotic target by genetic mutations or post-translational modification, (ii) deactivation of the antibiotic through hydrolysis or modification, such as phosphorylation by an enzyme, (iii) increased efflux of the antibiotic out of the cell by efflux pumps and porins, (iv) decreased influx/penetration of the antibiotic into the cell, through changes in cell wall structure; and overproduction of the antibiotic target through gene amplification [2]. However, one of bacteria’s preferred and commonly deployed strategies to overcome the effect of antimicrobials is the formation of biofilms. Over 90% of pathogenic bacterial species, including
Biofilm is a complex community of sessile microbial communities embedded in a self-producing polymeric matrix comprising exopolysaccharides, proteins, nucleic acids, and cell surface proteins [6, 7, 8]. As a community of microorganisms, biofilms constitute either a single microbial species or a combination of a different class of bacteria, fungi, protozoa, archaea, and yeast, with a unique ability to colonize almost any environmental niche, biotic or inert surfaces [9, 10, 11, 12, 13]. Biofilm enables microorganisms to withstand harsh environmental conditions such as nutrient deficiencies, high osmotic pressure, the low potential of hydrogen, oxidative stress, and antimicrobial insults [14]. The increased resistance of biofilms to antimicrobials arise from phenotypic cell variation and gene transcription. In particular, there is an exponential growth of microorganisms and genetic transfer of extrachromosomal elements via cell-to-cell communication system called quorum sensing [14, 15, 16, 17]. Quorum sensing is critical in the development and survival of biofilms; thus, it regulates the nutritional demands of microorganisms within the biofilm to meet the external supply of resources [18, 19]. In addition quorum sensing is essential for the biosynthesis and secretion of small molecule signals that activate a range of downstream processes including virulence and drug resistance mechanisms as seen in biofilms [20, 21].
The health risks of biofilms are enormous, which underscore their utilization in plant protection, bioremediation, wastewater treatment, and corrosion prevention in agricultural and industrial settings [22, 23, 24]. In particular, the biofilm grows on living human tissues such as the lungs and teeth and the surfaces of implanted biomedical devices, including contact lenses, central venous catheters [8, 25], prosthetic joints, pacemakers, and intrauterine devices [7]. Unlike single bacterial plankton cells, the treatment of biofilm-mediated infections is challenging owing to the decreased susceptibility to antimicrobial agents and other chemotherapeutics. The availability of qualitative (such as Congo red agar, microtitre plate, tube methods) and quantitative (including polymerase chain reaction (PCR)) techniques have enabled the detection and measurement of biofilms [26]. Conversely, the evaluation and screening of antimicrobials against biofilms are of great challenge. In particular, standard microdilution testing cannot evaluate the susceptibility of biofilms to antimicrobial drugs because these tests focus on planktonic (suspended) organisms rather than biofilm (surface-associated) organisms [7]. Instead, susceptibility must be determined directly against biofilm-associated organisms, preferably under conditions that mimic
Although nature has provided a plethora of natural products with varying chemotherapeutic properties to fight human infectious diseases, discovering new and effective antimicrobials has been slow. The decline in the efficacy of existing chemotherapy and the surge in drug resistance has triggered an expedient exploration of natural products, especially from plants and microbial origin, for their antibiofilm activity against biofilm-mediated human infections. Plant extracts and plant-derived chemical products, such as essential oils, flavonoids, terpenoids, have been shown in vitro to have antimicrobial and antibiofilm activity [27, 28, 29, 30, 31]. Secondary metabolites and other peptidic compounds from microorganisms also exhibit antagonistic effects against biofilms [6, 32]. These chemical constituents exert their action by inhibiting critical elements within a biofilm and/or terminating biofilm formation processes [33]. Given the unique nature of plants and microbes, natural products derived from these sources could provide an avenue for developing newly efficacious and clinically desirable chemotherapies against biofilms-mediated infections and their associated health consequences.
This chapter aims to provide a comprehensive summary of natural products from plants and microbial sources as potential sources of antibiofilm agents. Again, it highlights the strategies and model organisms used to identify and evaluate the antibiofilm capacity of these naturally isolated chemical compounds.
Biofilm formation represents a survival mechanism deployed by microorganisms in response to unfavorable environmental conditions [34]. Structurally, biofilms are a collection of adherent microorganisms in a milieu of an extracellular matrix consisting of polysaccharides, proteins, nucleic acids, and lipids. This unique architecture enables biofilms to cling firmly to surfaces of implanted body organs and biomedical devices and, more importantly, increase their resistance to antimicrobial therapy. The presence of bacterial secreted glycocalyx and degrading matrix enzymes reduces the antimicrobial concentration of which individual plankton cells within the biofilm are exposed [35, 36].
The morphogenesis of biofilms constitutes five distinct stages; namely, reversible attachment, irreversible adhesion, production of extracellular polymeric substances, biofilm maturation, and dispersal/detachment. As the initial step in biofilm formation, reversible attachment is characterized by the interaction between plankton cells and the conditioned surface. Fewer plankton cells move to the surface of the substrate by convection, pedesis, or sedimentation [37]. Consequently, chemotaxis directs bacterial cells along a nutrient gradient [38]. Upon reaching the surface of the substratum, the interaction between the cell surfaces and the substratum is dependent on the net sum of repulsive or attractive forces generated by the two characters [39, 40]. The presence of fimbriae, flagella, pili, and glycocalyx enables the microorganisms to overcome the repulsive forces (such as electrostatic, hydrophobic, Van der Waals, and hydration interactions) from the substratum and subsequently cling [39, 41, 42]. The rate of biofilms formation is influenced by the substrate’s physicochemical properties, including the surface roughness, hydrophobicity, surface charge, and the presence of conditioning films [41, 43, 44].
Furthermore, bacterial cells transition into an irreversible adhesion phase. Irreversible attachment occurs through the combined effect of short-range forces of the substrate (such as dipole-dipole, hydrogen, ionic and covalent interactions) and adhesive structures of the bacterial cells. The flagella and pili, for instance, are critically important in the attachment process of various strains of microorganisms [45, 46, 47, 48]. For example, Vatanyoopaisarn et al. demonstrated the firm clinging ability of wild-type
Moreover, the resident plankton cells produce extracellular polymeric substances (EPS), an essential biofilm component. Quorum sensing and cyclic-di-GMP mediated EPS formation [49, 50, 51, 52]. The formation of EPS promotes cohesion among bacteria and the adhesion of biofilms via hydrophobic and ionic interactions [49, 53, 54]. In addition, EPS is vital in constructing biofilms, maintaining biofilm architecture, quorum sensing, and genetic transfer among individual organisms within the biofilm [49, 55].
The resident bacterial cells proliferate into microcolonies mediated by autoinducers (AIs). AIs are chemical signaling molecules that permit intra-species and inter-species bacterial cell-to-cell communication [56, 57]. The surge in AIs activates critical enzymatic machinery in bacterial species for regulating the formation of microcolonies and the maturation of biofilms [52]. For example, the increase in AIs causes synchronous activation of the 15 gene-long epsA-O in
The terminal phase of biofilm formation, delineated as detachment or dispersal, is regulated by a complex mechanism constituting signal transduction, effector, and environmental factors [61]. Detachment/dispersal represents a unique phase in the life cycle, where plankton cells segregate and escape from biofilms to establish microcolonies on fresh surfaces [62, 63]. Of note, the dispersal phase of a biofilm is characterized by the detachment of plankton cells from hitherto biofilm, seeding or passive movement of plankton to new uncolonized surfaces, and clinging or attachment to substrates [61, 64, 65].
Several methods have been developed to study the antibiofilm activities of various compounds
The human epidermis organoid model has a tough methicillin-resistant
This method involves establishing bacterial biofilm by seeding the center of the skin model with 5 µL of 2
Among the most widely used models to investigate antibiofilm compounds is the skin wound model. It involves either causing damage to the skin (abrasion, burns or surgical excisions) and subsequently infecting the injured region with biofilm-forming bacteria, or inducing the formation of absess or wounds by seeding high-density biofilm forming bacteria subcutaneously. The commonly used clinically relevant organisms are
Various biofilms from disease and non-disease causing microorganisms results in the formation of dental caries. Dental caries results from the interation between diet and microbiota-matrix that occur on the oral surface [69]. This is mostly replicated in animal models using newly weaned rats. Prior treatmet with antbiotics is essential to elimintate existing microbiome. Subsequently, the animals are fed with cariogenic diet while also receiving the bacteria (e.g.
Periodontitis can as well be replicated in animal models using its associated bacteria (e.g.
The primary organism associated with biofilm lung infection in cystic fibrosis (CF) has been identified to be
Clinical isolates of
The ability of biofilm forming bacteria to grow and multiply on the surfaces of certain medical devices [75] has led to the discovery of this model. The preformation of biofilm on these surgically implanted foreign bodies affect the activity of defense cells [25]. This model can be executed using two (2) approaches. These are Site Specific Device Model where biofilm forming bacteria are introduced at the injection site after devices are placed in particular organ or region in humans for evaluation of antibiofilm activity, and Subcutaneous Device Model where deliberately colonized foreign bodies are inserted in the subcutaneous layer, mostly at the back of the animals [76]. In Site Specific Device Model, antibiofim activity is measured at the part of the device that made contact with bacteria or measured by bacterial recovery at injection site [75]. In Subcutaneous Device Model, the mobility of antibiofilm peptides can be restricted with the aim of preventing bacterial contact and eventually biofilm development [75]. However other modes of assessment like histological analysis, imaging by IVIS, scanning microscopy, and inflammatory response detection can also be employed in evaluating antibiofilm activity in test organisms [75].
Bacteria undergo an evolutionary mechanism to withstand harsh environmental conditions. The antibacterial agents derived from natural sources may serve as an effective alternative due to the presence of secondary metabolites, which possess selectional advantages against the biofilm-forming microorganisms [77, 78, 79]. Several methods have been reported as reliable protocols to investigate the anti-biofilm effects of natural products (Table 1) [80, 81]. Crystal violet assay is the widely accepted assay used to identify the anti-biofilm potentials of natural products despite the limitation, including the repeated washing that could lead to loss of cells and biofilm disruption [77, 80, 82, 83]. Other methods used to determine the antibiofilm effects of natural products are the Tissue Culture Plate (TCP) method [84], which exists as the most typical use standard method and is a comparatively reliable method to Congo Red Agar method (CRA) and Tube method [85]. Tube method and Congo red agar methods qualitatively detect biofilm formed, whiles the tissue culture plate method quantitatively determines the amount of biofilm formed [76]. Real time, conventional and multiplex PCR are other techniques used at molecular level to detect biofilm genes [86, 87, 88].
Method of biofilm detection | Principle | Aim |
---|---|---|
Tissue culture plate | It involves the staining of cells with crystal violet dye [77, 85, 91] | Biofilm detected quantitatively |
Tube method | Crystal violet staining where visible lining forms at the bottom and wall of the tube [85] | Biofilm detected qualitatively |
Congo red agar | Congo red staining formed black colonies crystals [84, 91, 92, 93] | Biofilm detected qualitatively |
Crystal violet assay | Quantifies the dye bound to biofilm [77, 94] | Quantitative determination of biofilm |
Real-time PCR, Multiplex PCR and conventional PCR | Amplification of DNA to the generation of fluorescence which can simply be detected [95, 96] | Detection of biofilm genes |
Methods to determine anti-biofilm effects of natural products.
In measuring the anti-biofilm activities of natural products, viability and matrix biomass can be assessed, where resazurin and crystal violet staining are performed sequentially in the same plate. Wheat germ agglutinin-Alexa Fluor 488 fluorescent conjugate is mainly used to stain the matrix, which is essential to measure the biofilm matrix, biomass, and viability to investigate the potencies of anti-biofilm effects of natural products [89, 90].
Plants have since time immemorial served as a source of therapeutics for the treatment and prevention of a plethora of diseases. This practice continues today, with more than 80% of people globally reportedly using various herbal remedies as a source of primary healthcare [97]. In mainstream medicine, plants have proven to be a prolific source of novel chemical matter from which essential drugs used to treat various diseases have been developed [98]. Galvanized by the emergence and spread of the antimicrobial drug resistance phenomena, numerous plant species have been thoroughly investigated as novel sources of antibacterial agents. To complement these strategies, the search for agents that can reverse resistance (resistance breakers) or target alternative mechanisms of overcoming antibacterial resistance, including biofilms, is being pursued [99, 100]. Plants have been identified as a potential oasis of such agents, prompting many studies in the last decade inspired towards the search for antibiofilm agents from plants. This section summarizes current studies on the investigation of antibiofilm agents, including crude extracts, fractions thereof, and pure compounds from plants (Tables 2 and 3; Figure 1).
Plant species | Comment |
---|---|
MBIC50 = 2 μg/ml against | |
MBIC50 = 7.21 μg/ml and MBEC50 = 57.71 μg/ml against | |
MBIC50 = 32 μg/ml against | |
Inhibited | |
IC50 = 53.6 μg/ml against | |
MBEC = 15.63, 3.9, 15.63 and 15.63 μg/ml against | |
50% inhibition at 1.41 μg/ml against | |
IC50 = 10.4 μg/ml against | |
IC50 = 17.7 μg/ml against |
Potent antibiofilm plant species.
IC, inhibitory concentration; MBIC, minimum biofilm inhibitory concentration; MBEC, minimum biofilm eradication concentration.
Compound and plant source | Comment |
---|---|
Xanthohumol ( | 100% inhibition of |
5-Hydroxymethylfurfural ( | 83% inhibition at 10 μg/ml against |
Lupulone ( | 100% inhibition of |
Cyanidin 3-O-glucoside ( | MICB50 = 3.3 μg/ml against |
Hodiendiol I ( | 78, 75 and 13% inhibition of |
Negletein ( | 72–88% reduction of biofilms of |
Syringopicroside ( | 92% inhibition at 1,28 μg/ml against |
Quercitin-3-glucoside ( | 92–98% reduction of biofilms of |
Panduratin A ( | Prevented |
Potent antibiofilm plant-derived compounds.
Chemical structures of some active plant derived antibiofilm compounds.
Despite being one of the least investigated, the Apiaceae plant family has produced some of the most prolific antibiofilm plant species. Among them is the annual herb
Chemical structures of (4aS, 5R, 8aS) 5, 8a-di-1-propyl-octahydronaphthalen-1-(2H)-one and thymol.
The Asteraceae is one of the most prominent species-rich plant families that produce highly active terpenoid compounds. A study on
Chemical structure of chondrillasterol.
An aqueous extract of
The medicinal plant
Along with the Asteraceae, the Fabaceae family is one plant species that has received substantial interest as a source of antibiofilm agents.
The Lamiaceae is a family of flowering plants commonly known as the mint family with a cosmopolitan distribution containing about 236 genera and about 6900–7200 species. Many plants in this family are aromatic and include widely used culinary herbs like basil, mint, rosemary, and sage [115]. Several Lamiaceae species have been interrogated for their antibiofilm activity and have shown pronounced activity against different biofilm stages of various microorganisms. One such species is the plant
The genus
Chemical structure of manool.
While
Chemical structure of malvin.
The Myristicaceae are flowering plants native to Africa, Asia, Pacific islands, and the Americas. The family consists of 20 genera and at least 500 species. Fruit of the Myristicaceae, particularly the lipid-rich aril surrounding the seed in some species, are essential as food for birds and mammals of tropical forests [122]. Plants in the family Myristicaceae with reported antibiofilm activities include
Chemical structure of macelignan.
Extracts of
Research has shown that some species of macrofungi have various chemical components with antibacterial, antifungal, antiviral, antioxidant, anticancer and antiprotozoal properties [137]. The extracts of some species, including
In addition, some of these compounds were found to inhibit biofilm formation [137].
Studies on the aqueous extracts of
A study by Borges et al demonstrated that ferulic and gallic acid inhibited biofilm formation in
Extracts from
Structures of compounds isolated from mushrooms with antibiofilm activities.
Melanin obtained from
Marine sponges produce an array of secondary metabolites such as enzymes, enzyme inhibitors, and antibiotics and represent an untapped reservoir of bioactive compounds [143]. These compounds serve as defense against environmental threats like microbial infection, competition for space, or overgrowth by fouling organisms [144].
Phorbaketals isolated from the Korean marine sponge
Chemical structures of phorbiketals isolated from
In addition, natural compounds such as collismycin, hydroxyl flavonoids, hydroxylbipyridine, and hydroxyl anthraquinones exhibited antibiofilm activity depending on the number and positions of hydroxyl groups in the backbone structures [145]. The planktonic cell growth of
In another study by Paul and Puglisi, cell-free supernatants (CFSs) isolated from the sponge-associated bacteria belonging to the genera
Species and strain | Major constituents | Antibiofilm activity against organisms |
---|---|---|
Glucose, mannose, galactose, galactosamine | ||
Glucose, mannose, galactose, galactosamine | ||
Mannose, arabinose, galacturonic acid |
Bacterial exopolysaccharide with antibiofilm activity against pathogenic bacteria [143].
In another study, marine sponge-derived
Existing literature proves the existence of compounds obtained from algae that possess antibiofilm properties against human pathogenic microbes. The scientific research community however, continues to discover such natural antibiofilm agents. These compounds do not exist in their pure forms but are isolated from crude extracts through a series of processes [148].
Marine algae produce certain sulfated polysaccharides that exhibit antimicrobial and antibiofilm activities [149]. Fucoidan F85 (Figure 9), a sulfated polysaccharide extracted from
Structure of fucoidan.
A study conducted by Maggs et al proves that marine brown algae,
Structure of a halogenated furanones.
The algal fronds of
Ethanolic extracts of
Methanol extract of
Silver nanoparticles associated with aqueous extract of
Several agents from natural products such as essential oils, honey etc. have shown great potential as bacterial biofilm inhibitors. These have been described below;
Essential oils from medicinal plants have received attention in recent times for their potential exploitations. This is as a result of the increasing reports of their composition and biochemicals to possess medicinal properties. A number of
The effect of
In an investigation to access the ability of
Essential oils from
A study by Moura et al. reported the antibiofilm activity of a lectin extracted from
Plant lectins are reported to also exhibit antibiofilm activities against pathogenic microorganisms. A typical example are, lectins extracted from
Chitosan is a polysaccharide composed of units of glucosamine (2-amino-2-deoxy-d-glucose) and
The antibiofilm activity of chitosan from crab and shrimp species indigenous to the Philippines was investigated against
Costa et al. also reported that chitosan demonstrated antibiofilm and biofilm eradication activity against the fungus
The exploration of new antibiotics to combat biofilm formation in resistant microbes has led to an increase interest evaluating the antibiofilm properties of honey. Manuka honey have demonstrated good antibiofilm forming activity against a range of bacteria, including S
Lu and colleagues studied the antibiofilm properties of four New Zealand based honeys; monofloral manuka honey, Medihoney (a manuka-based medical-grade honey), manuka-kanuka blend, and a clover honey on two
The biofilm inhibitory effect of Costa Rican Meliponini stingless bee honeys has also been reported against
Australian honey has also been reported to possess antibacterial and biofilm inhibitory activities. Sindi A and colleagues in their investigation reported that Western Australian honeys from
Peptides are small molecules made of 10–100 amino acids that are part of the innate immune response, and found among all classes of life contributing to the first line of defense against infections. In the search for an effective agent that can treat chronic infections, antimicrobial peptides (AMPs) have been shown to demonstrate antimicrobial, antibiofilm and biofilm eradication properties. Although there has not been much studies on the biofilm inhibitory action of AMP compared to its antibacterial activity, some naturally occurring AMP’s have been reported to exhibit strong antibiofilm activities against multidrug resistant as well as clinically isolated bacterial biofilms [179].
Cathelicidin peptides are one of the most important classes of AMP. Investigation of cathelicidin AMP, indicates that SMAP-29, BMAP-28, and BMAP-27 have antimicrobial activity and are able to significantly reduce biofilm formation by multidrug-resistant (MDR)
Hepcidin 20 alters the biofilm architecture of
The peptides lactoferrin, conjugated lactoferricin, melimine and citropin 1.1 have all shown good anti-biofilm activity against
Microorganisms, though form biofilms as a defense mechanism for survival, this action poses a threat to the healthcare system by compromising the therapeutic efficacy of antimicrobial agents and causing ascendancies in antimicrobial resistance. Natural products from plants and microorganisms provide a plethora of chemical compounds with antibiofilm properties capable of disrupting pre-formed biofilms or inhibiting the formation of new biofilms. Identifying novel antibiofilm compounds from these sources is essential to mitigate biofilm-mediated infections. Similarly, the exploration of model systems is critical for evaluating the antibiofilm properties of newly identified medicinal compounds. Altogether, understanding the antibiofilm potential of these natural products could serve as an impetus in antimicrobial drug discovery.
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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:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{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:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{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://mts.intechopen.com/storage/users/219081/images/system/219081.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:"Kafkas University",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:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",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:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{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. 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