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Marjana Tomiccanic - One of the best experts on this subject based on the ideXlab platform.
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clinical application of Growth Factors and cytokines in wound healing
Wound Repair and Regeneration, 2014Co-Authors: Stephan Barrientos, Olivera Stojadinovic, Harold Brem, Marjana TomiccanicAbstract:Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous Growth Factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various Growth Factors in the clinical management of nonhealing wounds (e.g., pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted an online search of Medline/PubMed and critically analyzed the literature regarding the role of Growth Factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies, and future research possibilities. In this review, we discuss four Growth Factors and cytokines currently being used on and off label for the healing of wounds. These include granulocyte-macrophage colony-stimulating factor, platelet-derived Growth factor, vascular endothelial Growth factor, and basic fibroblast Growth factor. While the clinical results of using Growth Factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy.
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Growth Factors and cytokines in wound healing
Wound Repair and Regeneration, 2008Co-Authors: Stephan Barrientos, Olivera Stojadinovic, Michael S Golinko, Harold Brem, Marjana TomiccanicAbstract:Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous Growth Factors, cytokines and chemokines. Of particular importance is the epidermal Growth factor (EGF) family, transforming Growth factor beta (TGF-b) family, fibroblast Growth factor (FGF) family, vascular endothelial Growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), plateletderived Growth factor (PDGF), connective tissue Growth factor (CTGF), interleukin (IL) family, and tumor nerosis factor-a family. Currently, patients are treated by three Growth Factors: PDGF-BB, bFGF ,a nd GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other Growth Factors may soon be available to patients. This review will focus on the specific roles of these Growth Factors and cytokines during the wound healing process. Wound healing is a complex process involving several overlapping stages that include inflammation, formation of granulation tissue, reepithelialization, matrix formation and remodeling. Upon injury to the skin, the epidermal barrier is disrupted and keratinocytes release prestored interleukin-1 (IL-1). IL-1 is the first signal that alerts surrounding cells to barrier damage. 1–11 In addition, blood components are released into the wound site activating the clotting cascade. The resulting clot induces hemostasis and provides a matrix for the influx of inflammatory cells. Platelets degranulate releasing alpha granules, which secrete Growth Factors such as: epidermal Growth factor (EGF), platelet-derived Growth factor (PDGF) and transforming Growth factor-beta (TGF-b). PDGF, along with proinflammatory cytokines like IL-1, are important in attracting neutrophils to the wound site to remove contaminating bacteria (reviewed in Hantash et al.). 12 With the help of TGF-b, monocytes are converted to macrophages which play an important role in augmenting the inflammatory response and tissue debridement. Macrophages initiate the development of granulation tissue and release a variety of proinflammatory cytokines (IL-1 and IL-6) and Growth Factors (fibroblast Growth factor [FGF], EGF, TGF-b, and PDGF). With the assistance of platelet released vascular endothelial Growth factor (VEGF) and FGF, endothelial cells proliferate and angiogenesis ensues. This process is essential for the synthesis, deposition, and organization of a new extracellular matrix (ECM). FGF, TGF-b, and PDGF then permit fibroblast infiltration. TGF-b and PDGF also initiate phenotypic changes in these cells converting fibroblasts into myofibroblasts which align themselves along the borders of the ECM to generate a constrictive force, facilitating wound closure (reviewed in
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Growth Factors and cytokines in wound healing
Wound Repair and Regeneration, 2008Co-Authors: Stephan Barrientos, Olivera Stojadinovic, Michael S Golinko, Harold Brem, Marjana TomiccanicAbstract:Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous Growth Factors, cytokines and chemokines. Of particular importance is the epidermal Growth factor (EGF) family, transforming Growth factor beta (TGF-beta) family, fibroblast Growth factor (FGF) family, vascular endothelial Growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived Growth factor (PDGF), connective tissue Growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. Currently, patients are treated by three Growth Factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other Growth Factors may soon be available to patients. This review will focus on the specific roles of these Growth Factors and cytokines during the wound healing process.
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perspective article Growth Factors and cytokines in wound healing
Wound Repair and Regeneration, 2008Co-Authors: Stephan Barrientos, Olivera Stojadinovic, Michael S Golinko, Harold Brem, Marjana TomiccanicAbstract:Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous Growth Factors, cytokines and chemokines. Of particular importance is the epidermal Growth factor (EGF) family, transforming Growth factor beta (TGF-β) family, fibroblast Growth factor (FGF) family, vascular endothelial Growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived Growth factor (PDGF), connective tissue Growth factor (CTGF), interleukin (IL) family, and tumor nerosis factor-α family. Currently, patients are treated by three Growth Factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other Growth Factors may soon be available to patients. This review will focus on the specific roles of these Growth Factors and cytokines during the wound healing process.
Stephan Barrientos - One of the best experts on this subject based on the ideXlab platform.
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clinical application of Growth Factors and cytokines in wound healing
Wound Repair and Regeneration, 2014Co-Authors: Stephan Barrientos, Olivera Stojadinovic, Harold Brem, Marjana TomiccanicAbstract:Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous Growth Factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various Growth Factors in the clinical management of nonhealing wounds (e.g., pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted an online search of Medline/PubMed and critically analyzed the literature regarding the role of Growth Factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies, and future research possibilities. In this review, we discuss four Growth Factors and cytokines currently being used on and off label for the healing of wounds. These include granulocyte-macrophage colony-stimulating factor, platelet-derived Growth factor, vascular endothelial Growth factor, and basic fibroblast Growth factor. While the clinical results of using Growth Factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy.
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Growth Factors and cytokines in wound healing
Wound Repair and Regeneration, 2008Co-Authors: Stephan Barrientos, Olivera Stojadinovic, Michael S Golinko, Harold Brem, Marjana TomiccanicAbstract:Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous Growth Factors, cytokines and chemokines. Of particular importance is the epidermal Growth factor (EGF) family, transforming Growth factor beta (TGF-b) family, fibroblast Growth factor (FGF) family, vascular endothelial Growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), plateletderived Growth factor (PDGF), connective tissue Growth factor (CTGF), interleukin (IL) family, and tumor nerosis factor-a family. Currently, patients are treated by three Growth Factors: PDGF-BB, bFGF ,a nd GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other Growth Factors may soon be available to patients. This review will focus on the specific roles of these Growth Factors and cytokines during the wound healing process. Wound healing is a complex process involving several overlapping stages that include inflammation, formation of granulation tissue, reepithelialization, matrix formation and remodeling. Upon injury to the skin, the epidermal barrier is disrupted and keratinocytes release prestored interleukin-1 (IL-1). IL-1 is the first signal that alerts surrounding cells to barrier damage. 1–11 In addition, blood components are released into the wound site activating the clotting cascade. The resulting clot induces hemostasis and provides a matrix for the influx of inflammatory cells. Platelets degranulate releasing alpha granules, which secrete Growth Factors such as: epidermal Growth factor (EGF), platelet-derived Growth factor (PDGF) and transforming Growth factor-beta (TGF-b). PDGF, along with proinflammatory cytokines like IL-1, are important in attracting neutrophils to the wound site to remove contaminating bacteria (reviewed in Hantash et al.). 12 With the help of TGF-b, monocytes are converted to macrophages which play an important role in augmenting the inflammatory response and tissue debridement. Macrophages initiate the development of granulation tissue and release a variety of proinflammatory cytokines (IL-1 and IL-6) and Growth Factors (fibroblast Growth factor [FGF], EGF, TGF-b, and PDGF). With the assistance of platelet released vascular endothelial Growth factor (VEGF) and FGF, endothelial cells proliferate and angiogenesis ensues. This process is essential for the synthesis, deposition, and organization of a new extracellular matrix (ECM). FGF, TGF-b, and PDGF then permit fibroblast infiltration. TGF-b and PDGF also initiate phenotypic changes in these cells converting fibroblasts into myofibroblasts which align themselves along the borders of the ECM to generate a constrictive force, facilitating wound closure (reviewed in
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Growth Factors and cytokines in wound healing
Wound Repair and Regeneration, 2008Co-Authors: Stephan Barrientos, Olivera Stojadinovic, Michael S Golinko, Harold Brem, Marjana TomiccanicAbstract:Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous Growth Factors, cytokines and chemokines. Of particular importance is the epidermal Growth factor (EGF) family, transforming Growth factor beta (TGF-beta) family, fibroblast Growth factor (FGF) family, vascular endothelial Growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived Growth factor (PDGF), connective tissue Growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. Currently, patients are treated by three Growth Factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other Growth Factors may soon be available to patients. This review will focus on the specific roles of these Growth Factors and cytokines during the wound healing process.
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perspective article Growth Factors and cytokines in wound healing
Wound Repair and Regeneration, 2008Co-Authors: Stephan Barrientos, Olivera Stojadinovic, Michael S Golinko, Harold Brem, Marjana TomiccanicAbstract:Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous Growth Factors, cytokines and chemokines. Of particular importance is the epidermal Growth factor (EGF) family, transforming Growth factor beta (TGF-β) family, fibroblast Growth factor (FGF) family, vascular endothelial Growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived Growth factor (PDGF), connective tissue Growth factor (CTGF), interleukin (IL) family, and tumor nerosis factor-α family. Currently, patients are treated by three Growth Factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other Growth Factors may soon be available to patients. This review will focus on the specific roles of these Growth Factors and cytokines during the wound healing process.
Kim Lewis - One of the best experts on this subject based on the ideXlab platform.
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Quinones are Growth Factors for the human gut microbiota
Microbiome, 2017Co-Authors: Kathrin Fenn, Philip Strandwitz, Eric Dimise, Shreya Gurubacharya, Eric J Stewart, Sarah Rubin, Jon Clardy, Kim LewisAbstract:BackgroundThe human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables Growth of uncultured species, suggesting the existence of Growth Factors in the natural environment not found in traditional cultivation media. One source of Growth Factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial Growth Factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel Growth Factors.ResultsBy testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an “induced” isolate formed a gradient of Growth around a cultivatable “helper.” This set included two novel species Faecalibacterium sp. KLE1255—belonging to the anti-inflammatory Faecalibacterium genus—and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting Growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for Growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced Growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically.ConclusionsOur data show that menaquinones are a major class of Growth Factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial Growth media or modulate the human gut microbiota by encouraging the Growth of important symbionts, such as Faecalibacterium species.
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quinones are Growth Factors for the human gut microbiota
Microbiome, 2017Co-Authors: Kathrin Fenn, Philip Strandwitz, Eric Dimise, Shreya Gurubacharya, Eric J Stewart, Sarah Rubin, Jon Clardy, Kim LewisAbstract:The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables Growth of uncultured species, suggesting the existence of Growth Factors in the natural environment not found in traditional cultivation media. One source of Growth Factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial Growth Factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel Growth Factors. By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an “induced” isolate formed a gradient of Growth around a cultivatable “helper.” This set included two novel species Faecalibacterium sp. KLE1255—belonging to the anti-inflammatory Faecalibacterium genus—and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting Growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for Growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced Growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically. Our data show that menaquinones are a major class of Growth Factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial Growth media or modulate the human gut microbiota by encouraging the Growth of important symbionts, such as Faecalibacterium species.
Kathrin Fenn - One of the best experts on this subject based on the ideXlab platform.
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Quinones are Growth Factors for the human gut microbiota
Microbiome, 2017Co-Authors: Kathrin Fenn, Philip Strandwitz, Eric Dimise, Shreya Gurubacharya, Eric J Stewart, Sarah Rubin, Jon Clardy, Kim LewisAbstract:BackgroundThe human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables Growth of uncultured species, suggesting the existence of Growth Factors in the natural environment not found in traditional cultivation media. One source of Growth Factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial Growth Factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel Growth Factors.ResultsBy testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an “induced” isolate formed a gradient of Growth around a cultivatable “helper.” This set included two novel species Faecalibacterium sp. KLE1255—belonging to the anti-inflammatory Faecalibacterium genus—and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting Growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for Growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced Growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically.ConclusionsOur data show that menaquinones are a major class of Growth Factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial Growth media or modulate the human gut microbiota by encouraging the Growth of important symbionts, such as Faecalibacterium species.
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quinones are Growth Factors for the human gut microbiota
Microbiome, 2017Co-Authors: Kathrin Fenn, Philip Strandwitz, Eric Dimise, Shreya Gurubacharya, Eric J Stewart, Sarah Rubin, Jon Clardy, Kim LewisAbstract:The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables Growth of uncultured species, suggesting the existence of Growth Factors in the natural environment not found in traditional cultivation media. One source of Growth Factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial Growth Factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel Growth Factors. By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an “induced” isolate formed a gradient of Growth around a cultivatable “helper.” This set included two novel species Faecalibacterium sp. KLE1255—belonging to the anti-inflammatory Faecalibacterium genus—and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting Growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for Growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced Growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically. Our data show that menaquinones are a major class of Growth Factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial Growth media or modulate the human gut microbiota by encouraging the Growth of important symbionts, such as Faecalibacterium species.
Lena Claessonwelsh - One of the best experts on this subject based on the ideXlab platform.
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function of fibroblast Growth Factors and vascular endothelial Growth Factors and their receptors in angiogenesis
Critical Reviews in Oncology Hematology, 2000Co-Authors: Par Gerwins, Erik Sköldenberg, Lena ClaessonwelshAbstract:Angiogenesis, formation of new vessels from pre-existing ones, results from stimulation of endothelial cells, which line the vessel wall. These cells will leave their resting state and start to digest the basement membrane, proliferate, migrate and eventually differentiate to form a hollow tube. All these steps can be induced by Growth Factors and this review will focus on two important types of angiogenic Growth Factors, vascular endothelial Growth factor (VEGF; also denoted vascular permeability factor, VPF) and fibroblast Growth factor (FGF). Both types of Factors bind to cell surface expressed receptors, which are ligand-stimulatable tyrosine kinases. Binding of the Growth Factors to their receptors leads to activation of the intrinsic tyrosine kinase and signal transduction to downstream signalling cascades. This results in transcriptional changes and biological responses. The molecular aspects of signalling cascades critical for endothelial cell proliferation and migration are beginning to be delineated. In contrast, signalling cascades leading to endothelial cell differentiation remain to be determined. Angiogenesis is essential for a number of physiological events such as embryonic development, ovulation, and wound healing. It has become increasingly clear that a number of diseases depend on angiogenesis. For future development of therapeutic tools, it is important to understand the molecular mechanisms that regulate angiogenesis.
