Background:Collagen peptides(CP),including tripeptides and elastin peptides(EP),are known for their in vitro and in vivo anti-skin aging effects.Despite positive results in animal models,the combination effects of CP ...Background:Collagen peptides(CP),including tripeptides and elastin peptides(EP),are known for their in vitro and in vivo anti-skin aging effects.Despite positive results in animal models,the combination effects of CP and EP and the bioavailability of CP in human studies,particularly in young and middle-aged women,remain underexplored.Objective:To evaluate the effects of an orally administered collagen drink combining CP and EP on the skin health of young and middle-aged women.Materials and Methods:A single-center,randomized,double-blind,parallel-controlled trial was conducted,utilizing the WONDERLABR fish collagen tripeptide beverage.Participants consumed the drink over an 8-week period.Results:Compared to the placebo group,the collagen drink group showed significant improvements in skin hydration(39.19%increase),transepidermal water loss(33.45%decrease),skin elasticity(25.37%increase),dermal collagen content(21.64%increase),pore size(7.94%decrease),wrinkle length(18.09%decrease),skin smoothness(2.85%improvement),and skin roughness(15.32%decrease).Overall pore volume decreased by 60%,and visual assessments indicated a decrease in skin luminosity by 15.20%and smoothness index by 22.55%.Mass spectrometry demonstrated a significant increase in collagen efficacy components,including blood pH and GPH levels(P<0.05).Conclusion:The study confirmed the combination nourishing and anti-skin aging effects of EP and CP on the skin of young and middle-aged women,demonstrating significant improvements in various skin parameters and good bioavailability of collagen peptides.展开更多
Skin aging shows an imbalance between synthesis and degradation of the extracellular matrix. The overproduction of degradative enzymes (MMPs) during the chronology- and photo-induced aging leads to a degradation of th...Skin aging shows an imbalance between synthesis and degradation of the extracellular matrix. The overproduction of degradative enzymes (MMPs) during the chronology- and photo-induced aging leads to a degradation of the elastic and collagen networks. In a model of collagen and elastin destruction, we showed that the gingival fibroblast was able to preserve these macromolecules by inhibiting the overproduction of metalloproteinases by overproduction of TIMP-1 and modulation of the inflammatory cytokines activity. The objective of this study is to evaluate the effect of the gingival fibroblasts on human skin. The results in vitro and ex vivo show that the gingival fibroblast protects the skin collagen and elastic network by the inhibition of MMPs which leads to an overproduction of the TIMP-1. Moreover, the gingival fibroblast modulates the activity of some enzymes responsible for the inflammation;they inhibit the IL-1β and stimulate the production of TGF-β1. In vivo studies with a duration of six months and 50 women with pronounced wrinkles show that the culture supernatant of gingival fibroblasts diluted to 5% leads to a statistically significant decrease in the number and length of wrinkles.展开更多
The bifurcation regions of intracranial and extracranial arteries are common sites for atherosclerosis,predisposing to ischaemic stroke.1 Previous studies have shown that the unique haemodynamics at the bifurca-tion m...The bifurcation regions of intracranial and extracranial arteries are common sites for atherosclerosis,predisposing to ischaemic stroke.1 Previous studies have shown that the unique haemodynamics at the bifurca-tion may lead to alterations in genes and proteins in this region.2 Elastin is closely associated with the progression of athero-sclerosis.3 However,under physiological conditions,the expression and distribu-tion of elastin in bifurcation regions have not yet been elucidated.Mice are the most frequently used animal model for studying atherosclerosis.This study focuses on carotid bifurcation,optimising the iDISCO(immunolabeling-enabled three-dimensional imaging of solvent-cleared organs)technique for whole tissue clearing and staining of the carotid artery in mice.4 These techniques,along with fluorescence micro-optical sectioning tomography(FMOST)technology,have also been used in studies on ischaemic stroke and kidney diseases,4 highlighting their potential for broader applications due to their high precision and three-dimensional imaging capabilities.5 Using FMOST technology in vitro,we have made a detailed visualisation of a U-shaped expression pattern of elastin at bifurcation regions for the first time.Specifically,elastin expression is found to be lowest at the bifurcation itself compared with the regions adjacent to or proximal to the bifurcation(figures 1A,B).Further-more,we observed disorganised arrange-ment of elastic fibres within the bifurcation zone(figures 1C,D).These findings provide important evidence linking elastic fibres to the pathogenesis of atherosclerosis at bifurcations and suggest the potential for more precise local therapies for athero-sclerosis,which could significantly advance precision medicine and reduce the poten-tial side effects on normal tissues.展开更多
Despite recent advances in extrusion bioprinting of cell-laden hydrogels,using nat-urally derived bioinks to biofabricate complex elastic tissues with both satisfying biological functionalities and superior mechanical...Despite recent advances in extrusion bioprinting of cell-laden hydrogels,using nat-urally derived bioinks to biofabricate complex elastic tissues with both satisfying biological functionalities and superior mechanical properties is hitherto an unmet challenge.Here,we address this challenge with precisely designed biological tough hydrogel bioinks featuring a double-network structure.The tough hydrogels con-sisted of energy-dissipative dynamically crosslinked glycosaminoglycan hyaluronic acid(o-nitrobenzyl-grafted hyaluronic acid)and elastin through Schiff’s base reac-tion,and free-radically polymerized gelatin methacryloyl.The incorporation of elastin further improved the elasticity,stretchability(∼170%strain),and tough-ness(∼45 kJ m-3)of the hydrogels due to the random coiling structure.We used this novel class of hydrogel bioinks to bioprint several complex elastic tissues with good shape retention.Furthermore,in vitro and in vivo experiments also demon-strated that the existence of elastin in the biocompatible bioinks facilitated improved cell behaviors and biological functions of bioprinted tissues,such as cell spreading and phenotype maintenance as well as tissue regeneration.The results confirmed the potential of the elastin-containing tough hydrogel bioinks for bioprinting of 3D complex elastic tissues with biological functionalities,which mayfind widespread applications in elastic tissue regeneration.展开更多
Cardiac extracellular matrices(ECM)play crucial functional roles in cardiac biomechanics.Previous studies have mainly focused on collagen,the major structural ECM in heart wall.The role of elastin in cardiac mechanics...Cardiac extracellular matrices(ECM)play crucial functional roles in cardiac biomechanics.Previous studies have mainly focused on collagen,the major structural ECM in heart wall.The role of elastin in cardiac mechanics,however,is poorly understood.In this study,we investigated the spatial distribution and microstructural morphologies of cardiac elastin in porcine left ventricles.We demonstrated that the epicardial elastin network had location-and depth-dependency,and the overall epicardial elastin fiber mapping showed certain correlation with the helical heart muscle fiber architecture.When compared to the epicardial layer,the endocardial layer was thicker and has a higher elastin-collagen ratio and a denser elastin fiber network;moreover,the endocardial elastin fibers were finer and more wavy than the epicardial elastin fibers,all suggesting various interface mechanics.The myocardial interstitial elastin fibers co-exist with the perimysial collagen to bind the cardiomyocyte bundles;some of the interstitial elastin fibers showed a locally aligned,hinge-like structure to connect the adjacent cardiomyocyte bundles.This collagen-elastin combination reflects an optimal design in which the collagen provides mechanical strength and elastin fibers facilitate recoiling during systole.Moreover,cardiac elastin fibers,along with collagen network,closely associated with the Purkinje cells,indicating that this ECM association could be essential in organizing cardiac Purkinje cells into“fibrous”and“branching”morphologies and serving as a protective feature when Purkinje fibers experience large deformations in vivo.In short,our observations provide a structural basis for future in-depth biomechanical investigations and biomimicking of this long-overlooked cardiac ECM component.展开更多
Background:The efficacy of balloon angioplasty for treating peripheral artery disease is influenced by various factors,some of them not yet totally understood.This study aimed to evaluate the role of elastin content i...Background:The efficacy of balloon angioplasty for treating peripheral artery disease is influenced by various factors,some of them not yet totally understood.This study aimed to evaluate the role of elastin content in vascular responses 28 days postangioplasty using uncoated and paclitaxel-coated balloons with the same platform in femoral arteries of a healthy porcine model.Methods:Eight animals underwent balloon angioplasty on the external and internal branches of femoral arteries.Histopathologic evaluation was conducted at follow-up to assess the elastin content,vascular damage,morphological features,and neointimal formation.Results:The elastin content was significantly higher in the external than in the internal femoral artery(p=0.0014).After balloon angioplasty,it was inversely correlated with vascular injury score(ρ=−0.4510,p=0.0096),neointimal inflammation(ρ=−0.3352,p=0.0607),transmural(ρ=−0.4474,p=0.0103)and circumferential(ρ=−0.4591,p=0.0082)smooth muscle cell loss,presence of proteoglycans(ρ=−0.5172,p=0.0024),fibrin deposition(ρ=−0.3496,p=0.0499),and adventitial fibrosis(ρ=−0.6229,p=0.0002).Neointimal formation inhibition with paclitaxel was evident only in arteries with disruption of the internal elastic lamina,with a significant smaller neointimal area in arteries treated with paclitaxel-coated balloons compared to uncoated balloons(median[Q1–Q3]:10.25[7.49–15.64]vs.24.44[18.96–30.52],p=0.0434).Conclusions:Elastin content varies between branches of the femoral artery and significantly influences the integrity of the internal elastic lamina,the vessel's adaptive response,and paclitaxel efficacy after balloon angioplasty.展开更多
为提高弹性蛋白肽(elastin peptide,EP)的理化性质与功能特性,该研究通过酶解联合微生物(副干酪乳杆菌YYS-K1)发酵制备弹性蛋白肽(elastin peptide by enzymolysis combined with microbial fermentation,EMEP),以单一蛋白酶解制备EP为...为提高弹性蛋白肽(elastin peptide,EP)的理化性质与功能特性,该研究通过酶解联合微生物(副干酪乳杆菌YYS-K1)发酵制备弹性蛋白肽(elastin peptide by enzymolysis combined with microbial fermentation,EMEP),以单一蛋白酶解制备EP为对照,比较EMEP和EP的理化性质和功能特性的差异。结果表明:EMEP的糖胺聚糖的含量较EP提高了约1.73倍;两种EP中氨基酸组成和必需氨基酸占比无明显差异,而EMEP中的Gly和Leu含量占比明显高于EP;分子质量分布结果表明,EMEP中<1000 Da肽段占比为89.37%,单一酶解制备的EP占比为89.19%。抗氧化结果表明,两种EP均具有一定的抗氧化能力,在质量浓度为40 mg/mL时,EMEP的DPPH自由基、ABTS阳离子自由基和超氧阴离子自由基清除率较EP分别提高29.59%、2.74%和8.45%;EP与EMEP均表现出良好的功能特性,其中质量浓度为40 mg/mL的EMEP可有效抑制白蛋白变性、AGEs生成以及胰脂肪酶和弹性蛋白酶的活性,抑制率分别达到了92.11%、70.14%、81.14%和83.33%,与单一蛋白酶解EP相比分别提高20.25%、12.66%、81.14%和20.85%。总之,酶解联合微生物发酵制备法有利于进一步提高EP的理化性质和功能特性,为开发高质量的弹性蛋白肽产品提供理论依据。展开更多
Background Elastin derived peptides can regulate melanocyte precursor development. Ultraviolet irradiation, infrared radiation and heat can increase the synthesis of tropoelastin in human skin epidermis. The aim of th...Background Elastin derived peptides can regulate melanocyte precursor development. Ultraviolet irradiation, infrared radiation and heat can increase the synthesis of tropoelastin in human skin epidermis. The aim of this study was to investigate whether the over expressed tropoelastin in epidermis has some role in melanogenesis of melanocytes. Methods A375 human melanoma cells were treated with different concentrations of kappa elastin for 24 hours. A375 human melanoma cells were randomly assigned to control, kappa elastin, and lactose pre-incubated groups. The cell viabilities were detected by the methyl thiazoleterazolium assay. Melanin content and tyrosinase activity in A375 melanoma cells were measured. The expressions of endothelin B receptor （ETBR） mRNA and c-kit mRNA in A375 melanoma cells were measured by quantative reverse transcription polymerase chain reaction. Results Fifty pg/ml of kappa elastin significantly increased the melanin content by 56.64% compared with the control （P 〈0.05）. Kappa elastin increased cellular tyrosinase activity by 46.73% compared with the control at 24 hours （P 〈0.05）. Kappa elastin increased the expressions of ETBR and c-kit mRNA levels by 2.13-fold and 2.47-fold compared with the controls, respectively. When pre-incubating cells with a lactose solution （10 mmol/L）, the inhibition on melanin production was 34.96% compared with the kappa elastin group （P 〈0.05）, tyrosinase activity was inhibited by 29.93% compared with kappa elastin group （P 〈0.05）, and the expressions of ETBR mRNA and c-kit mRNA were decreased by 1.56-fold and 0.82-fold compared with kappa elastin group, respectively. Conclusion Kappa elastin increased the melanogenesis in A375 melanoma cells via the stimulation of tyrosinase activity and the expression of ETBR and c-kit. The over expressed tropoelastin produced by keratinocytes might play a role in melanogenesis of epidermal melanocytes.展开更多
文摘Background:Collagen peptides(CP),including tripeptides and elastin peptides(EP),are known for their in vitro and in vivo anti-skin aging effects.Despite positive results in animal models,the combination effects of CP and EP and the bioavailability of CP in human studies,particularly in young and middle-aged women,remain underexplored.Objective:To evaluate the effects of an orally administered collagen drink combining CP and EP on the skin health of young and middle-aged women.Materials and Methods:A single-center,randomized,double-blind,parallel-controlled trial was conducted,utilizing the WONDERLABR fish collagen tripeptide beverage.Participants consumed the drink over an 8-week period.Results:Compared to the placebo group,the collagen drink group showed significant improvements in skin hydration(39.19%increase),transepidermal water loss(33.45%decrease),skin elasticity(25.37%increase),dermal collagen content(21.64%increase),pore size(7.94%decrease),wrinkle length(18.09%decrease),skin smoothness(2.85%improvement),and skin roughness(15.32%decrease).Overall pore volume decreased by 60%,and visual assessments indicated a decrease in skin luminosity by 15.20%and smoothness index by 22.55%.Mass spectrometry demonstrated a significant increase in collagen efficacy components,including blood pH and GPH levels(P<0.05).Conclusion:The study confirmed the combination nourishing and anti-skin aging effects of EP and CP on the skin of young and middle-aged women,demonstrating significant improvements in various skin parameters and good bioavailability of collagen peptides.
文摘Skin aging shows an imbalance between synthesis and degradation of the extracellular matrix. The overproduction of degradative enzymes (MMPs) during the chronology- and photo-induced aging leads to a degradation of the elastic and collagen networks. In a model of collagen and elastin destruction, we showed that the gingival fibroblast was able to preserve these macromolecules by inhibiting the overproduction of metalloproteinases by overproduction of TIMP-1 and modulation of the inflammatory cytokines activity. The objective of this study is to evaluate the effect of the gingival fibroblasts on human skin. The results in vitro and ex vivo show that the gingival fibroblast protects the skin collagen and elastic network by the inhibition of MMPs which leads to an overproduction of the TIMP-1. Moreover, the gingival fibroblast modulates the activity of some enzymes responsible for the inflammation;they inhibit the IL-1β and stimulate the production of TGF-β1. In vivo studies with a duration of six months and 50 women with pronounced wrinkles show that the culture supernatant of gingival fibroblasts diluted to 5% leads to a statistically significant decrease in the number and length of wrinkles.
基金supported by the National Natural Science Foundation of China grant number 81530037 to Yuming Xu,82401556 to Shen Li and 82301320 to Peipei Li.
文摘The bifurcation regions of intracranial and extracranial arteries are common sites for atherosclerosis,predisposing to ischaemic stroke.1 Previous studies have shown that the unique haemodynamics at the bifurca-tion may lead to alterations in genes and proteins in this region.2 Elastin is closely associated with the progression of athero-sclerosis.3 However,under physiological conditions,the expression and distribu-tion of elastin in bifurcation regions have not yet been elucidated.Mice are the most frequently used animal model for studying atherosclerosis.This study focuses on carotid bifurcation,optimising the iDISCO(immunolabeling-enabled three-dimensional imaging of solvent-cleared organs)technique for whole tissue clearing and staining of the carotid artery in mice.4 These techniques,along with fluorescence micro-optical sectioning tomography(FMOST)technology,have also been used in studies on ischaemic stroke and kidney diseases,4 highlighting their potential for broader applications due to their high precision and three-dimensional imaging capabilities.5 Using FMOST technology in vitro,we have made a detailed visualisation of a U-shaped expression pattern of elastin at bifurcation regions for the first time.Specifically,elastin expression is found to be lowest at the bifurcation itself compared with the regions adjacent to or proximal to the bifurcation(figures 1A,B).Further-more,we observed disorganised arrange-ment of elastic fibres within the bifurcation zone(figures 1C,D).These findings provide important evidence linking elastic fibres to the pathogenesis of atherosclerosis at bifurcations and suggest the potential for more precise local therapies for athero-sclerosis,which could significantly advance precision medicine and reduce the poten-tial side effects on normal tissues.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Numbers:2021-I2M-1-052,2017-I2M-1-007National Multidisciplinary Cooperative Diagnosis and Treatment Capacity Building Project for Major Diseases,Grant/Award Number:21025National Natural Science Foundation of China,Grant/Award Numbers:82371796,81871575。
文摘Despite recent advances in extrusion bioprinting of cell-laden hydrogels,using nat-urally derived bioinks to biofabricate complex elastic tissues with both satisfying biological functionalities and superior mechanical properties is hitherto an unmet challenge.Here,we address this challenge with precisely designed biological tough hydrogel bioinks featuring a double-network structure.The tough hydrogels con-sisted of energy-dissipative dynamically crosslinked glycosaminoglycan hyaluronic acid(o-nitrobenzyl-grafted hyaluronic acid)and elastin through Schiff’s base reac-tion,and free-radically polymerized gelatin methacryloyl.The incorporation of elastin further improved the elasticity,stretchability(∼170%strain),and tough-ness(∼45 kJ m-3)of the hydrogels due to the random coiling structure.We used this novel class of hydrogel bioinks to bioprint several complex elastic tissues with good shape retention.Furthermore,in vitro and in vivo experiments also demon-strated that the existence of elastin in the biocompatible bioinks facilitated improved cell behaviors and biological functions of bioprinted tissues,such as cell spreading and phenotype maintenance as well as tissue regeneration.The results confirmed the potential of the elastin-containing tough hydrogel bioinks for bioprinting of 3D complex elastic tissues with biological functionalities,which mayfind widespread applications in elastic tissue regeneration.
基金support:R01EB022018,R15HL140503,T32 HL134613 from NIH,UT STARS.
文摘Cardiac extracellular matrices(ECM)play crucial functional roles in cardiac biomechanics.Previous studies have mainly focused on collagen,the major structural ECM in heart wall.The role of elastin in cardiac mechanics,however,is poorly understood.In this study,we investigated the spatial distribution and microstructural morphologies of cardiac elastin in porcine left ventricles.We demonstrated that the epicardial elastin network had location-and depth-dependency,and the overall epicardial elastin fiber mapping showed certain correlation with the helical heart muscle fiber architecture.When compared to the epicardial layer,the endocardial layer was thicker and has a higher elastin-collagen ratio and a denser elastin fiber network;moreover,the endocardial elastin fibers were finer and more wavy than the epicardial elastin fibers,all suggesting various interface mechanics.The myocardial interstitial elastin fibers co-exist with the perimysial collagen to bind the cardiomyocyte bundles;some of the interstitial elastin fibers showed a locally aligned,hinge-like structure to connect the adjacent cardiomyocyte bundles.This collagen-elastin combination reflects an optimal design in which the collagen provides mechanical strength and elastin fibers facilitate recoiling during systole.Moreover,cardiac elastin fibers,along with collagen network,closely associated with the Purkinje cells,indicating that this ECM association could be essential in organizing cardiac Purkinje cells into“fibrous”and“branching”morphologies and serving as a protective feature when Purkinje fibers experience large deformations in vivo.In short,our observations provide a structural basis for future in-depth biomechanical investigations and biomimicking of this long-overlooked cardiac ECM component.
基金iVascular,S.L.U.,Camíde Can Ubach,11–Nave 3,08620 Sant Vicençdels Horts,Barcelona,Spain。
文摘Background:The efficacy of balloon angioplasty for treating peripheral artery disease is influenced by various factors,some of them not yet totally understood.This study aimed to evaluate the role of elastin content in vascular responses 28 days postangioplasty using uncoated and paclitaxel-coated balloons with the same platform in femoral arteries of a healthy porcine model.Methods:Eight animals underwent balloon angioplasty on the external and internal branches of femoral arteries.Histopathologic evaluation was conducted at follow-up to assess the elastin content,vascular damage,morphological features,and neointimal formation.Results:The elastin content was significantly higher in the external than in the internal femoral artery(p=0.0014).After balloon angioplasty,it was inversely correlated with vascular injury score(ρ=−0.4510,p=0.0096),neointimal inflammation(ρ=−0.3352,p=0.0607),transmural(ρ=−0.4474,p=0.0103)and circumferential(ρ=−0.4591,p=0.0082)smooth muscle cell loss,presence of proteoglycans(ρ=−0.5172,p=0.0024),fibrin deposition(ρ=−0.3496,p=0.0499),and adventitial fibrosis(ρ=−0.6229,p=0.0002).Neointimal formation inhibition with paclitaxel was evident only in arteries with disruption of the internal elastic lamina,with a significant smaller neointimal area in arteries treated with paclitaxel-coated balloons compared to uncoated balloons(median[Q1–Q3]:10.25[7.49–15.64]vs.24.44[18.96–30.52],p=0.0434).Conclusions:Elastin content varies between branches of the femoral artery and significantly influences the integrity of the internal elastic lamina,the vessel's adaptive response,and paclitaxel efficacy after balloon angioplasty.
基金This study was supported by a grant from the National Natural Science Foundation of China
文摘Background Elastin derived peptides can regulate melanocyte precursor development. Ultraviolet irradiation, infrared radiation and heat can increase the synthesis of tropoelastin in human skin epidermis. The aim of this study was to investigate whether the over expressed tropoelastin in epidermis has some role in melanogenesis of melanocytes. Methods A375 human melanoma cells were treated with different concentrations of kappa elastin for 24 hours. A375 human melanoma cells were randomly assigned to control, kappa elastin, and lactose pre-incubated groups. The cell viabilities were detected by the methyl thiazoleterazolium assay. Melanin content and tyrosinase activity in A375 melanoma cells were measured. The expressions of endothelin B receptor （ETBR） mRNA and c-kit mRNA in A375 melanoma cells were measured by quantative reverse transcription polymerase chain reaction. Results Fifty pg/ml of kappa elastin significantly increased the melanin content by 56.64% compared with the control （P 〈0.05）. Kappa elastin increased cellular tyrosinase activity by 46.73% compared with the control at 24 hours （P 〈0.05）. Kappa elastin increased the expressions of ETBR and c-kit mRNA levels by 2.13-fold and 2.47-fold compared with the controls, respectively. When pre-incubating cells with a lactose solution （10 mmol/L）, the inhibition on melanin production was 34.96% compared with the kappa elastin group （P 〈0.05）, tyrosinase activity was inhibited by 29.93% compared with kappa elastin group （P 〈0.05）, and the expressions of ETBR mRNA and c-kit mRNA were decreased by 1.56-fold and 0.82-fold compared with kappa elastin group, respectively. Conclusion Kappa elastin increased the melanogenesis in A375 melanoma cells via the stimulation of tyrosinase activity and the expression of ETBR and c-kit. The over expressed tropoelastin produced by keratinocytes might play a role in melanogenesis of epidermal melanocytes.
