Hepatic sinusoidal endothelial cells(HSEC)are the most important cells that constitute the microcirculation barrier of liver.Clinically,W-P bodies have been detected in the HSEC cells of most patients with liver fibro...Hepatic sinusoidal endothelial cells(HSEC)are the most important cells that constitute the microcirculation barrier of liver.Clinically,W-P bodies have been detected in the HSEC cells of most patients with liver fibrosis,and these bodies have become the synthesis and storage sites of vW factor,ET-1 and other factors of liver fibrosis;during pathological stimulation,W-P bodies will excrete the above factors into the cytoplasm,which can make the structure and function of HSEC maladjusted,cause the disturbance of liver microcirculation,and aggravate the process of liver fibrosis.However,previous studies have found that Plumbagin,the active ingredient of Guangxi specialty ethnic medicine,has the definite function of promoting blood circulation and removing blood stasis and anti-liver fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived from it as follows:the role of Plumbagin in promoting blood circulation and removing blood stasis and anti-liver fibrosis is produced by affecting the formation quantity of W-P bodies,affecting the synthesis and storage of the contents of W-P bodies,and interfering with their exocytosis ability.展开更多
Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturb...Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturbance of liver is one of the important pathogenesis of chronic liver disease,the improvement of microcirculation is beneficial to the recovery of liver function and the delay of liver fibrosis.Hepatic stellate cells are the core cells of hepatic fibrosis,and also the most critical cells that affect the microcirculation of the liver.While TLR4/MyD88/NF-κB and TLR4/MyD88/MAPKs which are based on the action of hepatic stellate cells are two pathways that have very important influence on the inflammatory response of liver,the proliferation and apoptosis of hepatic stellate cells,and the secretion of fibrogenic cytokines.It was found that Plumbapin,the active ingredient of Guangxi specialty ethnic medicine,has the definite effect of promoting blood circulation and removing blood stasis and anti-hepatic fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived as follows:the pharmacological effect of Plumbapin on anti-hepatic fibrosis,promoting blood circulation and removing stasis was based on the influence of TLR4/MyD88/NF-κB and MAPKs signal pathway.展开更多
BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary...BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary dysfunction.AIM To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients.METHODS A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023.These patients were divided into two groups:control group(n=53)and observation group(n=60).In the control group,patients received routine therapy in combination with methylprednisolone tablets,while those in the observation group received routine therapy together with pirfenidone.After applying these distinct treatment approaches to the two groups,we assessed several parameters,including the overall effectiveness of clinical therapy,the occurrence of adverse reactions(e.g.,nausea,vomiting,and anorexia),symptom severity scores,pulmonary function index levels,inflammatory marker levels,and the 6-min walk distance before and after treatment in both groups.RESULTS The observation group exhibited significantly higher rates than the control group after therapy,with a clear distinction(P<0.05).After treatment,the observation group experienced significantly fewer adverse reactions than the control group,with a noticeable difference(P<0.05).When analyzing the symptom severity scores between the two groups of patients after treatment,the observation group had significantly lower scores than the control group,with a distinct difference(P<0.05).When comparing the pulmonary function index levels between the two groups of patients after therapy,the observation group displayed significantly higher levels than the control group,with a noticeable difference(P<0.05).Evaluating the inflammatory marker data(C-reactive protein,interleukin-2[IL-2],and IL-8)between the two groups of patients after therapy,the observation group exhibited significantly lower levels than the control group,with significant disparities(P<0.05).Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group,with a marked difference(P<0.05).CONCLUSION Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function,elevate inflammatory factor levels,and increase the distance covered in the 6-min walk test.This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.展开更多
[ Objectives ] This study was conducted to evaluate the action of the aqueous extract of a medicinal plant Plumbago zeylanica L. in the reversal of dime- thylnitrosamine （DMN） -induced hepatic fibrosis in rats, and ...[ Objectives ] This study was conducted to evaluate the action of the aqueous extract of a medicinal plant Plumbago zeylanica L. in the reversal of dime- thylnitrosamine （DMN） -induced hepatic fibrosis in rats, and to provide a scientific basis for the utilization of P. zeylanica in treatment of hepatic fibrosis. [Meth- ods ] Hepatic fibrosis in rats was induced by intraperitoneal injection of DMN. The rats were then given the aqueous extract of P. zeylanica at high, medium or low concentration by garage for five weeks. Serum level of alanine aminotransferase （ALT） was determined by lactate dehydrogenase （LDH）-release assay, and serum level of aspartate transaminase （AST） was measured by UV-malate dehydrogenase （MDH） assay. Serum levels of total bilirubin （TBIL）, direct bilirubin （DBIL） and indirect bilirubin （1BIL） were measured by vanadate oxidation assay. Four indices of hepatic fibrosis （hyaluronic acid, laminin, procollagen type III and colla- gen type IV） were determined by radioimmunoassay （RIA） assay. Morphological damage of liver tissue was observed by hematoxylin-eosin staining （H＆E stai- ning）. Immunohistochemical staining was performed to determine the location and area of deposited collagen type I, collagen type III and ct-smeoth muscle actin （a-SMA） in liver tissue. [ Results] Compared with the negative control （rats with diseased fiver and untreated with P. zeylanica aqueous extract）, the serum lev- els of ALT, AST, TBIL, DBIL and IBIL were significantly decreased by P. zeylanica aqueous extract; the levels of the four serum indices of hepatic fibrosis were also obviously reduced. H＆E staining showed that hepatic fibrosis in rats was obviously inhibited or even reversed by P. zeylanica aqueous extract. Immunohisto- chemical staining proved that the aqueous extract of P. zeylanica significantly reduced the area and coloration of collagen type I, collagen type III and ct-SMA in rat liver. [ Conclusions] The aqueous extract of P. zeylanica has a definite effect in reversal of DMN-indueed hepatic fibrosis in rat by promoting the recovery of liver function, reversal of histopathological changes and reducing fibrotic collagen.展开更多
[Objectives] The aim was to investigate the intervening effect of sodium aescinate on pulmonary fibrosis in rats with acute lung injury( ALI). [Methods] The rats were randomly divided into normal group,model group and...[Objectives] The aim was to investigate the intervening effect of sodium aescinate on pulmonary fibrosis in rats with acute lung injury( ALI). [Methods] The rats were randomly divided into normal group,model group and sodium aescinate group. The rat model of ALI was induced by administration of oleic acid. The rats in the sodium aescinate group were intravenously injected with sodium aescinate according to the amount of 4 mg/kg for 14 consecutive d. Then,11 rats were selected randomly from each group and slaughtered on Day 1 and Day 14,respectively after last administration. The body mass index,arterial partial pressure of oxygen( PaO_2),oxygenation index( PaO_2/FiO_2),lung index,wet/dry mass ratio of lung,serum IL-1β,TNF-α,PC Ⅲ and TGF-β1 levels of the rats were analyzed. [Results]No significant differences were found in body mass index,lung index or lung wet/dry mass ratio among different groups. Compared with the model group,the PaO_2 and PaO_2/FiO_2 ratio increased significantly( P < 0. 05),the serum IL-1β,TNF-α,PC Ⅲ and TGF-β1 levels declined significantly( P <0. 05),the lung histopathological damage was reduced,and the semi-quantitative histological score( IQA) of damaged lung tissue decreased significantly( P < 0. 01). [Conclusions]Sodium aescinate can reduce the levels of inflammatory factors in rats with ALI,with certain intervening on pulmonary effect.展开更多
Liver fibrosis is a wound-healing response to chronic injuries, characterized by the excessive accumulation of extracellular matrix or scar tissue within the liver;in addition, its formation is associated with multipl...Liver fibrosis is a wound-healing response to chronic injuries, characterized by the excessive accumulation of extracellular matrix or scar tissue within the liver;in addition, its formation is associated with multiple cytokines as well as several cell types and a variety of signaling pathways. When liver fibrosis is not well controlled, it can progress to liver cirrhosis, but it is reversible in principle. Thus far, no efficient therapy is available for treatment of liver fibrosis. Although liver transplantation is the preferred strategy, there are many challenges remaining in this approach, such as shortage of donor organs, immunological rejection, and surgical complications. Hence, there is a great need for an alternative therapeutic strategy. Currently, mesenchymal stem cell (MSC) therapy is considered a promising therapeutic strategy for the treatment of liver fibrosis;advantageously, the characteristics of MSCs are continuous self-renewal, proliferation, multipotent differentiation, and immunomodulatory activities. The human umbilical cord-derived (hUC)-MSCs possess not only the common attributes of MSCs but also more stable biological characteristics, relatively easy accessibility, abundant source, and no ethical issues (e.g., bone marrow being the adult source), making hUC-MSCs a good choice for treatment of liver fibrosis. In this review, we summarize the biological characteristics of hUC-MSCs and their paracrine effects, exerted by secretion of various cytokines, which ultimately promote liver repair through several signaling pathways. Additionally, we discuss the capacity of hUC-MSCs to differentiate into hepatocyte-like cells for compensating the function of existing hepatocytes, which may aid in amelioration of liver fibrosis. Finally, we discuss the current status of the research field and its future prospects.展开更多
Fibrosis is the hyperactivation of fibroblasts that results in excessive accumulation of extracellular matrix,which is involved in numerous pathological changes and diseases.Adipose-derived stem cells(ASCs)are promisi...Fibrosis is the hyperactivation of fibroblasts that results in excessive accumulation of extracellular matrix,which is involved in numerous pathological changes and diseases.Adipose-derived stem cells(ASCs)are promising seed cells for regenerative medicine due to their bountiful source,low immunogenicity and lack of ethical issues.Their anti-fibrosis,immunomodulation,angiogenesis and other therapeutic effects have made them suitable for treating fibrosis-related diseases.Here,we review the literature on ASCs treating fibrosis,elaborate and discuss their mechanisms of action,changes in disease environment,ways to enhance therapeutic effects,as well as current preclinical and clinical studies,in order to provide a general picture of ASCs treating fibrotic diseases.展开更多
BACKGROUND Sustained injury,through radiotherapy,burns or surgical trauma,can result in fibrosis,displaying an excessive deposition of extracellular matrix(ECM),persisting inflammatory reaction,and reduced vasculariza...BACKGROUND Sustained injury,through radiotherapy,burns or surgical trauma,can result in fibrosis,displaying an excessive deposition of extracellular matrix(ECM),persisting inflammatory reaction,and reduced vascularization.The increasing recognition of fibrosis as a cause for disease and mortality,and increasing use of radiotherapy causing fibrosis,stresses the importance of a decent anti-fibrotic treatment.AIM To obtain an in-depth understanding of the complex mechanisms underlying fibrosis,and more specifically,the potential mechanisms-of-action of adiposederived stomal cells(ADSCs)in realizing their anti-fibrotic effect.METHODS A systematic review of the literature using PubMed,Embase and Web of Science was performed by two independent reviewers.RESULTS The injection of fat grafts into fibrotic tissue,releases ADSC into the environment.ADSCs’capacity to directly differentiate into key cell types(e.g.,ECs,fibroblasts),as well as to secrete multiple paracrine factors(e.g.,hepatocyte growth factor,basis fibroblast growth factor,IL-10),allows them to alter different mechanisms underlying fibrosis in a combined approach.ADSCs favor ECM degradation by impacting the fibroblast-to-myofibroblast differentiation,favoring matrix metalloproteinases over tissue inhibitors of metalloproteinases,positively influencing collagen organization,and inhibiting the pro-fibrotic effects of transforming growth factor-β1.Furthermore,they impact elements of both the innate and adaptive immune response system,and stimulate angiogenesis on the site of injury(through secretion of pro-angiogenic cytokines like stromal cell-derived factor-1 and vascular endothelial growth factor).CONCLUSION This review shows that understanding the complex interactions of ECM accumulation,immune response and vascularization,is vital to fibrosis treatments’effectiveness like fat grafting.It details how ADSCs intelligently steer this complex system in an anti-fibrotic or pro-angiogenic direction,without falling into extreme dilation or stimulation of a single aspect.Detailing this combined approach,has brought fat grafting one step closer to unlocking its full potential as a non-anecdotal treatment for fibrosis.展开更多
In this letter,we review the article“Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”.We focus specifically on the detrimental effects of alcoho...In this letter,we review the article“Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”.We focus specifically on the detrimental effects of alcohol-associated liver disease(ALD)on human health.Given its insidious onset and increasing incidence,increasing awareness of ALD can contribute to reducing the prevalence of liver diseases.ALD comprises a spectrum of several different disorders,including liver steatosis,steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.The pathogenesis of ALD is exceedingly complex.Previous studies have shown that peroxisome proliferator-activated receptors(PPARs)regulate lipid metabolism,glucose homeostasis and inflammatory responses within the organism.Additionally,their dysfunction is a major contributor to the progression of ALD.Elafibranor is an oral,dual PPARαandδagonist.The effectiveness of elafibranor in the treatment of ALD remains unclear.In this letter,we emphasize the harm of ALD and the burden it places on society.Furthermore,we summarize the clinical management of all stages of ALD and present new insights into its pathogenesis and potential therapeutic targets.Additionally,we discuss the mechanisms of action of PPARαandδagonists,the significance of their antifibrotic effects on ALD and future research directions.展开更多
基金Supported by the Research Project of National Natural Science Foundation of China(No.81960761,81960751,81680705)Basic Ability Improvement Project for Young and Middle-aged Teachers in Colleges and Universities of Guangxi(No.2018KY1149)。
文摘Hepatic sinusoidal endothelial cells(HSEC)are the most important cells that constitute the microcirculation barrier of liver.Clinically,W-P bodies have been detected in the HSEC cells of most patients with liver fibrosis,and these bodies have become the synthesis and storage sites of vW factor,ET-1 and other factors of liver fibrosis;during pathological stimulation,W-P bodies will excrete the above factors into the cytoplasm,which can make the structure and function of HSEC maladjusted,cause the disturbance of liver microcirculation,and aggravate the process of liver fibrosis.However,previous studies have found that Plumbagin,the active ingredient of Guangxi specialty ethnic medicine,has the definite function of promoting blood circulation and removing blood stasis and anti-liver fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived from it as follows:the role of Plumbagin in promoting blood circulation and removing blood stasis and anti-liver fibrosis is produced by affecting the formation quantity of W-P bodies,affecting the synthesis and storage of the contents of W-P bodies,and interfering with their exocytosis ability.
基金the Research Project of National Natural Science Foundation of China(81960761,81960751,81680705)Basic Ability Improvement Project for Young and Middle-aged Teachers in Colleges and Universities of Guangxi(2018KY1149)Natural Science Foundation of Guangxi Province(2020JJA140257).
文摘Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturbance of liver is one of the important pathogenesis of chronic liver disease,the improvement of microcirculation is beneficial to the recovery of liver function and the delay of liver fibrosis.Hepatic stellate cells are the core cells of hepatic fibrosis,and also the most critical cells that affect the microcirculation of the liver.While TLR4/MyD88/NF-κB and TLR4/MyD88/MAPKs which are based on the action of hepatic stellate cells are two pathways that have very important influence on the inflammatory response of liver,the proliferation and apoptosis of hepatic stellate cells,and the secretion of fibrogenic cytokines.It was found that Plumbapin,the active ingredient of Guangxi specialty ethnic medicine,has the definite effect of promoting blood circulation and removing blood stasis and anti-hepatic fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived as follows:the pharmacological effect of Plumbapin on anti-hepatic fibrosis,promoting blood circulation and removing stasis was based on the influence of TLR4/MyD88/NF-κB and MAPKs signal pathway.
文摘BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary dysfunction.AIM To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients.METHODS A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023.These patients were divided into two groups:control group(n=53)and observation group(n=60).In the control group,patients received routine therapy in combination with methylprednisolone tablets,while those in the observation group received routine therapy together with pirfenidone.After applying these distinct treatment approaches to the two groups,we assessed several parameters,including the overall effectiveness of clinical therapy,the occurrence of adverse reactions(e.g.,nausea,vomiting,and anorexia),symptom severity scores,pulmonary function index levels,inflammatory marker levels,and the 6-min walk distance before and after treatment in both groups.RESULTS The observation group exhibited significantly higher rates than the control group after therapy,with a clear distinction(P<0.05).After treatment,the observation group experienced significantly fewer adverse reactions than the control group,with a noticeable difference(P<0.05).When analyzing the symptom severity scores between the two groups of patients after treatment,the observation group had significantly lower scores than the control group,with a distinct difference(P<0.05).When comparing the pulmonary function index levels between the two groups of patients after therapy,the observation group displayed significantly higher levels than the control group,with a noticeable difference(P<0.05).Evaluating the inflammatory marker data(C-reactive protein,interleukin-2[IL-2],and IL-8)between the two groups of patients after therapy,the observation group exhibited significantly lower levels than the control group,with significant disparities(P<0.05).Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group,with a marked difference(P<0.05).CONCLUSION Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function,elevate inflammatory factor levels,and increase the distance covered in the 6-min walk test.This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.
基金Supported by National Natural Science Foundation of China(81403189,81460628,81660705,81560690)Scientific Research Project for Higher Education of Guangxi Zhuang Autonomous Region Education Department(YB2014182)
文摘[ Objectives ] This study was conducted to evaluate the action of the aqueous extract of a medicinal plant Plumbago zeylanica L. in the reversal of dime- thylnitrosamine （DMN） -induced hepatic fibrosis in rats, and to provide a scientific basis for the utilization of P. zeylanica in treatment of hepatic fibrosis. [Meth- ods ] Hepatic fibrosis in rats was induced by intraperitoneal injection of DMN. The rats were then given the aqueous extract of P. zeylanica at high, medium or low concentration by garage for five weeks. Serum level of alanine aminotransferase （ALT） was determined by lactate dehydrogenase （LDH）-release assay, and serum level of aspartate transaminase （AST） was measured by UV-malate dehydrogenase （MDH） assay. Serum levels of total bilirubin （TBIL）, direct bilirubin （DBIL） and indirect bilirubin （1BIL） were measured by vanadate oxidation assay. Four indices of hepatic fibrosis （hyaluronic acid, laminin, procollagen type III and colla- gen type IV） were determined by radioimmunoassay （RIA） assay. Morphological damage of liver tissue was observed by hematoxylin-eosin staining （H＆E stai- ning）. Immunohistochemical staining was performed to determine the location and area of deposited collagen type I, collagen type III and ct-smeoth muscle actin （a-SMA） in liver tissue. [ Results] Compared with the negative control （rats with diseased fiver and untreated with P. zeylanica aqueous extract）, the serum lev- els of ALT, AST, TBIL, DBIL and IBIL were significantly decreased by P. zeylanica aqueous extract; the levels of the four serum indices of hepatic fibrosis were also obviously reduced. H＆E staining showed that hepatic fibrosis in rats was obviously inhibited or even reversed by P. zeylanica aqueous extract. Immunohisto- chemical staining proved that the aqueous extract of P. zeylanica significantly reduced the area and coloration of collagen type I, collagen type III and ct-SMA in rat liver. [ Conclusions] The aqueous extract of P. zeylanica has a definite effect in reversal of DMN-indueed hepatic fibrosis in rat by promoting the recovery of liver function, reversal of histopathological changes and reducing fibrotic collagen.
基金Supported by Scientific Research Project of Traditional Chinese Medicine Bureau of Guangdong Province(20172093)
文摘[Objectives] The aim was to investigate the intervening effect of sodium aescinate on pulmonary fibrosis in rats with acute lung injury( ALI). [Methods] The rats were randomly divided into normal group,model group and sodium aescinate group. The rat model of ALI was induced by administration of oleic acid. The rats in the sodium aescinate group were intravenously injected with sodium aescinate according to the amount of 4 mg/kg for 14 consecutive d. Then,11 rats were selected randomly from each group and slaughtered on Day 1 and Day 14,respectively after last administration. The body mass index,arterial partial pressure of oxygen( PaO_2),oxygenation index( PaO_2/FiO_2),lung index,wet/dry mass ratio of lung,serum IL-1β,TNF-α,PC Ⅲ and TGF-β1 levels of the rats were analyzed. [Results]No significant differences were found in body mass index,lung index or lung wet/dry mass ratio among different groups. Compared with the model group,the PaO_2 and PaO_2/FiO_2 ratio increased significantly( P < 0. 05),the serum IL-1β,TNF-α,PC Ⅲ and TGF-β1 levels declined significantly( P <0. 05),the lung histopathological damage was reduced,and the semi-quantitative histological score( IQA) of damaged lung tissue decreased significantly( P < 0. 01). [Conclusions]Sodium aescinate can reduce the levels of inflammatory factors in rats with ALI,with certain intervening on pulmonary effect.
基金Supported by the Natural Science Foundation of Jilin Province of China,No.20190201010JC
文摘Liver fibrosis is a wound-healing response to chronic injuries, characterized by the excessive accumulation of extracellular matrix or scar tissue within the liver;in addition, its formation is associated with multiple cytokines as well as several cell types and a variety of signaling pathways. When liver fibrosis is not well controlled, it can progress to liver cirrhosis, but it is reversible in principle. Thus far, no efficient therapy is available for treatment of liver fibrosis. Although liver transplantation is the preferred strategy, there are many challenges remaining in this approach, such as shortage of donor organs, immunological rejection, and surgical complications. Hence, there is a great need for an alternative therapeutic strategy. Currently, mesenchymal stem cell (MSC) therapy is considered a promising therapeutic strategy for the treatment of liver fibrosis;advantageously, the characteristics of MSCs are continuous self-renewal, proliferation, multipotent differentiation, and immunomodulatory activities. The human umbilical cord-derived (hUC)-MSCs possess not only the common attributes of MSCs but also more stable biological characteristics, relatively easy accessibility, abundant source, and no ethical issues (e.g., bone marrow being the adult source), making hUC-MSCs a good choice for treatment of liver fibrosis. In this review, we summarize the biological characteristics of hUC-MSCs and their paracrine effects, exerted by secretion of various cytokines, which ultimately promote liver repair through several signaling pathways. Additionally, we discuss the capacity of hUC-MSCs to differentiate into hepatocyte-like cells for compensating the function of existing hepatocytes, which may aid in amelioration of liver fibrosis. Finally, we discuss the current status of the research field and its future prospects.
基金Supported by the National Natural Science Foundation of China,No.81670444and the CAMS Innovation Fund for Medical Sciences(CIFMS),No.2020-I2MC&T-A-004.
文摘Fibrosis is the hyperactivation of fibroblasts that results in excessive accumulation of extracellular matrix,which is involved in numerous pathological changes and diseases.Adipose-derived stem cells(ASCs)are promising seed cells for regenerative medicine due to their bountiful source,low immunogenicity and lack of ethical issues.Their anti-fibrosis,immunomodulation,angiogenesis and other therapeutic effects have made them suitable for treating fibrosis-related diseases.Here,we review the literature on ASCs treating fibrosis,elaborate and discuss their mechanisms of action,changes in disease environment,ways to enhance therapeutic effects,as well as current preclinical and clinical studies,in order to provide a general picture of ASCs treating fibrotic diseases.
文摘BACKGROUND Sustained injury,through radiotherapy,burns or surgical trauma,can result in fibrosis,displaying an excessive deposition of extracellular matrix(ECM),persisting inflammatory reaction,and reduced vascularization.The increasing recognition of fibrosis as a cause for disease and mortality,and increasing use of radiotherapy causing fibrosis,stresses the importance of a decent anti-fibrotic treatment.AIM To obtain an in-depth understanding of the complex mechanisms underlying fibrosis,and more specifically,the potential mechanisms-of-action of adiposederived stomal cells(ADSCs)in realizing their anti-fibrotic effect.METHODS A systematic review of the literature using PubMed,Embase and Web of Science was performed by two independent reviewers.RESULTS The injection of fat grafts into fibrotic tissue,releases ADSC into the environment.ADSCs’capacity to directly differentiate into key cell types(e.g.,ECs,fibroblasts),as well as to secrete multiple paracrine factors(e.g.,hepatocyte growth factor,basis fibroblast growth factor,IL-10),allows them to alter different mechanisms underlying fibrosis in a combined approach.ADSCs favor ECM degradation by impacting the fibroblast-to-myofibroblast differentiation,favoring matrix metalloproteinases over tissue inhibitors of metalloproteinases,positively influencing collagen organization,and inhibiting the pro-fibrotic effects of transforming growth factor-β1.Furthermore,they impact elements of both the innate and adaptive immune response system,and stimulate angiogenesis on the site of injury(through secretion of pro-angiogenic cytokines like stromal cell-derived factor-1 and vascular endothelial growth factor).CONCLUSION This review shows that understanding the complex interactions of ECM accumulation,immune response and vascularization,is vital to fibrosis treatments’effectiveness like fat grafting.It details how ADSCs intelligently steer this complex system in an anti-fibrotic or pro-angiogenic direction,without falling into extreme dilation or stimulation of a single aspect.Detailing this combined approach,has brought fat grafting one step closer to unlocking its full potential as a non-anecdotal treatment for fibrosis.
文摘目的:探究阿法骨化醇联合熊去氧胆酸(UDCA)对原发性胆汁性胆管炎(PBC)的疗效及抗肝纤维化作用。方法:2022年6月至2023年6月山西省汾阳医院收治的符合纳入标准的25羟维生素D即25(OH)D_(3)<50 nmol/L的PBC患者70例,随机分为治疗组35例和对照组35例,治疗组为阿法骨化醇联合UDCA治疗;对照组为UDCA单独治疗。持续治疗6月后检查患者的25(OH)D_(3)、血小板、肝功能、免疫球蛋白、肝硬度(LSM)和药物不良反应,计算FIB-4指数(fibrosis 4 score)、天冬氨酸转氨酶和血小板比率指数(aspartate aminotransferase to platelet ratio index,APRI)评分、GLOBE评分和UK-PBC评分,满足正态分布的计量资料采用均数±标准差(x±s)表示,两组间比较用独立样本t检验;不满足正态分布的计量资料采用M(P_(25),P_(75))表示,两组间比较采用Mann-Whitney U检验;应答率比较用卡方检验。结果:治疗后对照组和治疗组应答率分别为42.85%和71.42%;γ-谷氨酰转肽酶(GGT)分别为160(128,194)、85(72,102)U/L,碱性磷酸酶(ALP)分别为156(123,264)、110(56,141)U/L;免疫球蛋白M(IgM)分别为(3.51±0.84)、(2.71±0.81)g/L;25(OH)D_(3)分别为(40.21±3.25)、(57.06±14.76)nmol/L;肝硬度分别为10.8(8.3,15.1)、8.9(6.7,12.2)Kpa;FIB-4指数分别为2.28(0.99,3.66)、1.46(0.97,2.55);APRI评分分别为0.65(0.33,1.09)、0.30(0.17,0.53);GLOBE评分分别为0.85±0.73、0.13±0.51;UK-PBC评分分别为0.024(0.018,0.060)、0.021(0.012,0.033),差异均有统计学意义(均P<0.05)。结论:阿法骨化醇联合UDCA较单独应用UDCA可显著提高PBC患者治疗应答率,而且阿法骨化醇一定程度上可改善肝纤维化,有助于PBC的病情改善,无不良反应。
基金Supported by National Natural Science Foundation of China,No.82172754 and No.81874208Natural Science Foundation Project of Hubei Province,No.2021CFB562.
文摘In this letter,we review the article“Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”.We focus specifically on the detrimental effects of alcohol-associated liver disease(ALD)on human health.Given its insidious onset and increasing incidence,increasing awareness of ALD can contribute to reducing the prevalence of liver diseases.ALD comprises a spectrum of several different disorders,including liver steatosis,steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.The pathogenesis of ALD is exceedingly complex.Previous studies have shown that peroxisome proliferator-activated receptors(PPARs)regulate lipid metabolism,glucose homeostasis and inflammatory responses within the organism.Additionally,their dysfunction is a major contributor to the progression of ALD.Elafibranor is an oral,dual PPARαandδagonist.The effectiveness of elafibranor in the treatment of ALD remains unclear.In this letter,we emphasize the harm of ALD and the burden it places on society.Furthermore,we summarize the clinical management of all stages of ALD and present new insights into its pathogenesis and potential therapeutic targets.Additionally,we discuss the mechanisms of action of PPARαandδagonists,the significance of their antifibrotic effects on ALD and future research directions.
