Idiopathic pulmonary fibrosis(IPF),characterized by aggravated alveolar destruc-tion and fibrotic matrix deposition,tendentiously experiences the stage called acute exacerbation IPF(AE-IPF)and progresses to multiple o...Idiopathic pulmonary fibrosis(IPF),characterized by aggravated alveolar destruc-tion and fibrotic matrix deposition,tendentiously experiences the stage called acute exacerbation IPF(AE-IPF)and progresses to multiple organ damage,especially liver injury.Recent studies have found a variety of immune microenvironment disorders associated with elevated IPF risk and secondary organ injury,whereas current animal models induced with bleomycin(BLM)could not completely reflect the pathologi-cal manifestations of AE-IPF patients in clinic,and the exact underlying mechanisms are not yet fully explored.In the current study,we established an AE-IPF model by tracheal administration of a single dose of BLM and then repeated administrations of lipopolysaccharide in mice.This mouse model successfully recapitulated the clinical features of AE-IPF,including excessive intrapulmonary inflammation and fibrosis and extrapulmonary manifestations,as indicated by significant upregulation of Il6,Tnfa,Il1b,Tgfb,fibronectin,and Col1a1 in both lungs and liver and elevated serum aspartate transaminase and alanine transaminase levels.These effects might be attributed to the regulation of Th17 cells.By sharing this novel murine model,we expect to pro-vide an appropriate experimental platform to investigate the pathogenesis of AE-IPF coupled with liver injury and contribute to the discovery and development of targeted interventions.展开更多
Diabetic kidney disease(DKD)is a prevalent complication of diabetes,often leading to end-stage renal disease.Animal models have been widely used to study the pathogenesis of DKD and evaluate potential therapies.Howeve...Diabetic kidney disease(DKD)is a prevalent complication of diabetes,often leading to end-stage renal disease.Animal models have been widely used to study the pathogenesis of DKD and evaluate potential therapies.However,current animal models often fail to fully capture the pathological characteristics of renal injury observed in clinical patients with DKD.Additionally,modeling DKD is often a time-consuming,costly,and labor-intensive process.The current review aims to summarize modeling strategies in the establishment of DKD animal models by utilizing meta-analysis related methods and to aid in the optimization of these models for future research.A total of 1215 articles were retrieved with the keywords of“diabetic kidney disease”and“animal experiment”in the past 10 years.Following screening,84 articles were selected for inclusion in the meta-analysis.Review manager 5.4.1 was employed to analyze the changes in blood glucose,glycosylated hemoglobin,total cholesterol,triglyceride,serum creatinine,blood urea nitrogen,and urinary albumin excretion rate in each model.Renal lesions shown in different models that were not suitable to be included in the metaanalysis were also extensively discussed.The above analysis suggested that combining various stimuli or introducing additional renal injuries to current models would be a promising avenue to overcome existing challenges and limitations.In conclusion,our review article provides an in-depth analysis of the limitations in current DKD animal models and proposes strategies for improving the accuracy and reliability of these models that will inspire future research efforts in the DKD research field.展开更多
Objective:Cholangiocarcinoma(CCA)is a rare but highly malignant hepatobiliary cancer with a very poor prognosis and limited treatment options.CCA is commonly associated with chronic cholestasis and significantly eleva...Objective:Cholangiocarcinoma(CCA)is a rare but highly malignant hepatobiliary cancer with a very poor prognosis and limited treatment options.CCA is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids(CBAs),which are correlated with bile duct obstruction.展开更多
Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoh...Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases.However,current treatment options are limited,highlighting the urgent need for the development of new therapies.As a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver fibrosis.Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still controversial.This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic diseases.The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted.Finally,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed.In summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.展开更多
Nonalcoholic fatty liver disease(NAFLD)has become one of the most prominent causes of chronic liver diseases and malignancies.However,few therapy has been approved.Radix Bupleuri(RB)is the most frequently used herbal ...Nonalcoholic fatty liver disease(NAFLD)has become one of the most prominent causes of chronic liver diseases and malignancies.However,few therapy has been approved.Radix Bupleuri(RB)is the most frequently used herbal medicine for the treatment of liver diseases.In the current study,we aim to systemically evaluate the therapeutic effects of saikosaponin A(SSa)and saikosaponin D(SSd),the major bioactive monomers in RB,against NAFLD and to investigate the underlying mechanisms.Our results demonstrated that both SSa and SSd improved diet-induced NAFLD.Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes,like Lipe and Lipg.SSd profoundly suppressed the fatty acid biosynthesis by downregulating Fasn and Acaca expression and promoted fatty acid degradation by inducing Acox1 and Cpt1 a expression.Bioinformatic analysis further predicted the implication of master transcription factors,including peroxisome proliferator-activated receptor alpha(PPARα),in the protective effects of SSa and SSd.These results were further confirmed in vitro in mouse primary hepatocytes.In summary,our study uncoded the complicated mechanisms underlying the promising anti-steatosis activities of saikosaponins(SSs),and provided critical evidence inspiring the discovery of innovative therapies based on SSa and SSd for the treatment of NAFLD and related complications.展开更多
This article attempts to detail time series characteristics of PM2.5 concentration in Guangzhou(China)from 1 June 2012 to 31 May 2013 based on wavelet analysis tools,and discuss its spatial distribution using geograph...This article attempts to detail time series characteristics of PM2.5 concentration in Guangzhou(China)from 1 June 2012 to 31 May 2013 based on wavelet analysis tools,and discuss its spatial distribution using geographic information system software and a modified land use regression model.In this modified model,an important variable(land use data)is substituted for impervious surface area,which can be obtained conveniently from remote sensing imagery through the linear spectral mixture analysis method.Impervious surface has higher precision than land use data because of its sub-pixel level.Seasonal concentration pattern and day-by-day change feature of PM2.5 in Guangzhou with a micro-perspective are discussed and understood.Results include:(1)the highest concentration of PM2.5 occurs in October and the lowest in July,respectively;(2)average concentration of PM2.5 in winter is higher than in other seasons;and(3)there are two high concentration zones in winter and one zone in spring.展开更多
基金supported by the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(grant no.:ZYYCXTD-C-202006 to XG and Xiaojiaoyang Li)Beijing Municipal Science and Technology Commission(grant no.:7212174 to Xiaojiaoyang Li)+2 种基金National Natural Science Foundation of China(grant no.:82004045 to Xiaojiaoyang Li)Beijing Nova Program of Science and Technology(grant no.:Z191100001119088 to Xiaojiaoyang Li)the Young Elite Scientists Sponsorship Program by CACM(grant no.:2020-QNRC2-01 to Xiaojiaoyang Li).
文摘Idiopathic pulmonary fibrosis(IPF),characterized by aggravated alveolar destruc-tion and fibrotic matrix deposition,tendentiously experiences the stage called acute exacerbation IPF(AE-IPF)and progresses to multiple organ damage,especially liver injury.Recent studies have found a variety of immune microenvironment disorders associated with elevated IPF risk and secondary organ injury,whereas current animal models induced with bleomycin(BLM)could not completely reflect the pathologi-cal manifestations of AE-IPF patients in clinic,and the exact underlying mechanisms are not yet fully explored.In the current study,we established an AE-IPF model by tracheal administration of a single dose of BLM and then repeated administrations of lipopolysaccharide in mice.This mouse model successfully recapitulated the clinical features of AE-IPF,including excessive intrapulmonary inflammation and fibrosis and extrapulmonary manifestations,as indicated by significant upregulation of Il6,Tnfa,Il1b,Tgfb,fibronectin,and Col1a1 in both lungs and liver and elevated serum aspartate transaminase and alanine transaminase levels.These effects might be attributed to the regulation of Th17 cells.By sharing this novel murine model,we expect to pro-vide an appropriate experimental platform to investigate the pathogenesis of AE-IPF coupled with liver injury and contribute to the discovery and development of targeted interventions.
文摘Diabetic kidney disease(DKD)is a prevalent complication of diabetes,often leading to end-stage renal disease.Animal models have been widely used to study the pathogenesis of DKD and evaluate potential therapies.However,current animal models often fail to fully capture the pathological characteristics of renal injury observed in clinical patients with DKD.Additionally,modeling DKD is often a time-consuming,costly,and labor-intensive process.The current review aims to summarize modeling strategies in the establishment of DKD animal models by utilizing meta-analysis related methods and to aid in the optimization of these models for future research.A total of 1215 articles were retrieved with the keywords of“diabetic kidney disease”and“animal experiment”in the past 10 years.Following screening,84 articles were selected for inclusion in the meta-analysis.Review manager 5.4.1 was employed to analyze the changes in blood glucose,glycosylated hemoglobin,total cholesterol,triglyceride,serum creatinine,blood urea nitrogen,and urinary albumin excretion rate in each model.Renal lesions shown in different models that were not suitable to be included in the metaanalysis were also extensively discussed.The above analysis suggested that combining various stimuli or introducing additional renal injuries to current models would be a promising avenue to overcome existing challenges and limitations.In conclusion,our review article provides an in-depth analysis of the limitations in current DKD animal models and proposes strategies for improving the accuracy and reliability of these models that will inspire future research efforts in the DKD research field.
文摘Objective:Cholangiocarcinoma(CCA)is a rare but highly malignant hepatobiliary cancer with a very poor prognosis and limited treatment options.CCA is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids(CBAs),which are correlated with bile duct obstruction.
基金supported by the National Key Research and Development Program on Modernization of Traditional Chinese Medicine(Grant No.2022YFC3502104,China)supports from VA Merit Award 5 I01 BX005730+2 种基金National Institutes of Health Grant R01 R01DK-057543 to Huiping Zhou(USA)National High-Level Talents Special Support Program to Xiaojiaoyang Li(China)Fundamental Research Funds for the Central Universities(Grant No.2023-JYBJBZD-046 to Xiaojiaoyang Li,China)。
文摘Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases.However,current treatment options are limited,highlighting the urgent need for the development of new therapies.As a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver fibrosis.Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still controversial.This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic diseases.The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted.Finally,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed.In summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.
基金supported by grants from the National Natural Science Foundation of China(Nos.81773997 and 81073148 to Rong SunNo.82004029 to Runping Liu+3 种基金No.82004045 to Xiaojiaoyang Li)Beijing University of Chinese Medicine(No.2020-JYB-ZDGG-038 to Runping Liu,China)supported by grants from Beijing Nova Program of Science&Technology(Nos.Z201100006820025 and Z191100001119088,China)supported by research fund‘Traditional Chinese medicine pharmacology and toxicology expert(No.ts201511107)’from the Taishan Scholar Project of Shandong Province(China)。
文摘Nonalcoholic fatty liver disease(NAFLD)has become one of the most prominent causes of chronic liver diseases and malignancies.However,few therapy has been approved.Radix Bupleuri(RB)is the most frequently used herbal medicine for the treatment of liver diseases.In the current study,we aim to systemically evaluate the therapeutic effects of saikosaponin A(SSa)and saikosaponin D(SSd),the major bioactive monomers in RB,against NAFLD and to investigate the underlying mechanisms.Our results demonstrated that both SSa and SSd improved diet-induced NAFLD.Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes,like Lipe and Lipg.SSd profoundly suppressed the fatty acid biosynthesis by downregulating Fasn and Acaca expression and promoted fatty acid degradation by inducing Acox1 and Cpt1 a expression.Bioinformatic analysis further predicted the implication of master transcription factors,including peroxisome proliferator-activated receptor alpha(PPARα),in the protective effects of SSa and SSd.These results were further confirmed in vitro in mouse primary hepatocytes.In summary,our study uncoded the complicated mechanisms underlying the promising anti-steatosis activities of saikosaponins(SSs),and provided critical evidence inspiring the discovery of innovative therapies based on SSa and SSd for the treatment of NAFLD and related complications.
基金This work is supported by the National Nature Science Foundation of China[grant number:41201432],the National Science Foundation of Tibet[grant number:2016ZR-TU-05]the Foundation for Innovative Research for Young Teachers in Higher Educational Institutions of Tibet[grant number:QCZ2016-07].
文摘This article attempts to detail time series characteristics of PM2.5 concentration in Guangzhou(China)from 1 June 2012 to 31 May 2013 based on wavelet analysis tools,and discuss its spatial distribution using geographic information system software and a modified land use regression model.In this modified model,an important variable(land use data)is substituted for impervious surface area,which can be obtained conveniently from remote sensing imagery through the linear spectral mixture analysis method.Impervious surface has higher precision than land use data because of its sub-pixel level.Seasonal concentration pattern and day-by-day change feature of PM2.5 in Guangzhou with a micro-perspective are discussed and understood.Results include:(1)the highest concentration of PM2.5 occurs in October and the lowest in July,respectively;(2)average concentration of PM2.5 in winter is higher than in other seasons;and(3)there are two high concentration zones in winter and one zone in spring.