The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the c...The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.展开更多
Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we id...Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.展开更多
Background:Myocardial infarction(MI)is an acute condition in which the heart mus-cle dies due to the lack of blood supply.Previous research has suggested that au-tophagy and angiogenesis play vital roles in the preven...Background:Myocardial infarction(MI)is an acute condition in which the heart mus-cle dies due to the lack of blood supply.Previous research has suggested that au-tophagy and angiogenesis play vital roles in the prevention of heart failure after MI,and miR-106a is considered to be an important regulatory factor in MI.But the specific mechanism remains unknown.In this study,using cultured venous endothelial cells and a rat model of MI,we aimed to identify the potential target genes of miR-106a and discover the mechanisms of inhibiting autophagy and angiogenesis.Methods:We first explored the biological functions of miR-106a on autophagy and angiogenesis on endothelial cells.Then we identified ATG7,which was the down-stream target gene of miR-106a.The expression of miR-106a and ATG7 was investi-gated in the rat model of MI.Results:We found that miR-106a inhibits the proliferation,cell cycle,autophagy and angiogenesis,but promoted the apoptosis of vein endothelial cells.Moreover,ATG7 was identified as the target of miR-106a,and ATG7 rescued the inhibition of autophagy and angiogenesis by miR-106a.The expression of miR-106a in the rat model of MI was decreased but the expression of ATG7 was increased in the infarction areas.Conclusion:Our results indicate that miR-106a may inhibit autophagy and angiogenesis by targeting ATG7.This mechanism may be a potential therapeutic treatment for MI.展开更多
Gastroesophageal reflux disease(GERD)is a digestive system disease characterized by uncomfortable symptoms caused by reflux of gastric contents.It has increased sharply with the development of my country’s society an...Gastroesophageal reflux disease(GERD)is a digestive system disease characterized by uncomfortable symptoms caused by reflux of gastric contents.It has increased sharply with the development of my country’s society and economy.If there is no reasonable and effective Prevention and treatment measures will inevitably increase the financial burden of patients,and also pose a major threat to the quality of life and health of patients.Cell signal transduction mediated by various receptors participates in the regulation mechanism of the body's various levels of biological functions.By inhibiting or activating its functions,the purpose of curing diseases can be achieved,and cell signal transduction has been used in traditional Chinese medicine.Studying.The theory of"adjusting the central axis"was explored by Professor Xie Sheng through decades of clinical experience.It has been proven in practice to treat GERD.It starts from the model of TCM viscera and expounds that the pathogenesis of GERD involves multiple viscera.Multi-system and multi-factor,explain the correlation of the disease with a variety of zang-fu syndromes,and use this as a basis to guide the clinical use of hidden prescriptions.The back-shu pointer therapy can prevent GERD by correcting the unbalanced state of the viscera and qi machine,and promoting the junction of the two channels of Ren and Du.Based on the theory of"adjusting the hub by the pivot",this article expounds the pathogenesis of GERD from the perspective of traditional Chinese medicine.By consulting the literature and combining with the previous research,it proposes to analyze the methods and methods of Backshu pointer therapy to prevent and treat GERD from the AMPK/ULK1 mediated autophagy pathway.展开更多
In the state of acute myocardial ischemia,miRNA expression can regulate related genes and proteins,reduce myocardial cell damage,and thus play a protective role in the myocardium.However,the specific mechanism still n...In the state of acute myocardial ischemia,miRNA expression can regulate related genes and proteins,reduce myocardial cell damage,and thus play a protective role in the myocardium.However,the specific mechanism still needs to be further explored.Recent studies have found that the opening of the mitoKATP channel can regulate mitochondrial autophagy,and the initiation of miRNA-DNA methylation plays a regulatory role in inducing cell autophagy.The applicant research team previously found that Qishen Yiqi Dropping Pills could significantly improve myocardial ischemia by mediating MitokATP channels to regulate mitochondrial autophagy.,and animal experiments have confirmed that miR-155 plays a significant role in the aspect of autophagy regulates,inflammatory reaction and Vascular smooth muscle cell migration.Therefore,the applicant innovatively proposed that Qishen Yiqi Dropping Pills can regulate miRNA155-DNA methylation to mediate the opening of mitoKATP,thereby regulating mitochondrial autophagy and improving myocardial ischemia.In this paper,the association between mitochondrial autophagy and oxidative stress injury after myocardial ischemia was described,and the possible mechanism of Qisen Yiqi dropping pills regulating mitochondrial autophagy by regulating miRNA155-DNA methylation to mediate MitokATP to improve myocardial ischemia reperfusion injury was discussed,so as to provide theoretical ideas for related research.展开更多
With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn pu...With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.展开更多
基金supported by the National Natural Science Foundation of China(No.81703001)the Natural Science Foundation of Hebei Province(No.H2021406021),Hebei Province Medical Science Research Project(Nos.20210247,20221335)Hebei Province Government-Funded Clinical Medical Outstanding Talents Project,Chengde Medical University Scientific Research Major Projects(No.KY2020005).
文摘The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.
基金National Natural Science Foundation of China(81870850)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX23_0322)。
文摘Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.
基金National Natural Science Foundation of China,Grant/Award Number:32070542Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2021A1515010873 and 2022A1515011455+1 种基金Breed Industry Innovation Park of Guangdong Xiaoerhua Pig,Grant/Award Number:2022-4408X1-43010402-0019Hainan Provincial Natural Science Foundation,Grant/Award Number:818MS132。
文摘Background:Myocardial infarction(MI)is an acute condition in which the heart mus-cle dies due to the lack of blood supply.Previous research has suggested that au-tophagy and angiogenesis play vital roles in the prevention of heart failure after MI,and miR-106a is considered to be an important regulatory factor in MI.But the specific mechanism remains unknown.In this study,using cultured venous endothelial cells and a rat model of MI,we aimed to identify the potential target genes of miR-106a and discover the mechanisms of inhibiting autophagy and angiogenesis.Methods:We first explored the biological functions of miR-106a on autophagy and angiogenesis on endothelial cells.Then we identified ATG7,which was the down-stream target gene of miR-106a.The expression of miR-106a and ATG7 was investi-gated in the rat model of MI.Results:We found that miR-106a inhibits the proliferation,cell cycle,autophagy and angiogenesis,but promoted the apoptosis of vein endothelial cells.Moreover,ATG7 was identified as the target of miR-106a,and ATG7 rescued the inhibition of autophagy and angiogenesis by miR-106a.The expression of miR-106a in the rat model of MI was decreased but the expression of ATG7 was increased in the infarction areas.Conclusion:Our results indicate that miR-106a may inhibit autophagy and angiogenesis by targeting ATG7.This mechanism may be a potential therapeutic treatment for MI.
基金National Natural Science Foundation(No.82004299)Enhancement Program of Evidence-based Therapy of Digestive System Diseases(gastroesophageal reflux disease)with Traditional Chinese Medicine(No.2019XZZX-XH003)Innovation Planning Program of Postgraduate Students Education of Guangxi University of Traditional Chinese Medicine in 2020(No.YCSY2020030)。
文摘Gastroesophageal reflux disease(GERD)is a digestive system disease characterized by uncomfortable symptoms caused by reflux of gastric contents.It has increased sharply with the development of my country’s society and economy.If there is no reasonable and effective Prevention and treatment measures will inevitably increase the financial burden of patients,and also pose a major threat to the quality of life and health of patients.Cell signal transduction mediated by various receptors participates in the regulation mechanism of the body's various levels of biological functions.By inhibiting or activating its functions,the purpose of curing diseases can be achieved,and cell signal transduction has been used in traditional Chinese medicine.Studying.The theory of"adjusting the central axis"was explored by Professor Xie Sheng through decades of clinical experience.It has been proven in practice to treat GERD.It starts from the model of TCM viscera and expounds that the pathogenesis of GERD involves multiple viscera.Multi-system and multi-factor,explain the correlation of the disease with a variety of zang-fu syndromes,and use this as a basis to guide the clinical use of hidden prescriptions.The back-shu pointer therapy can prevent GERD by correcting the unbalanced state of the viscera and qi machine,and promoting the junction of the two channels of Ren and Du.Based on the theory of"adjusting the hub by the pivot",this article expounds the pathogenesis of GERD from the perspective of traditional Chinese medicine.By consulting the literature and combining with the previous research,it proposes to analyze the methods and methods of Backshu pointer therapy to prevent and treat GERD from the AMPK/ULK1 mediated autophagy pathway.
基金Regional Fund Project of National Natural Science Foundation of China(No.81460712)the Young and Middle-aged Teachers’Scientific Research Basic Ability Enhancement Project of Guangxi Universities(No.2020KY07026)Guangxi Graduate Education Innovation Program(No.YCXJ2021035)。
文摘In the state of acute myocardial ischemia,miRNA expression can regulate related genes and proteins,reduce myocardial cell damage,and thus play a protective role in the myocardium.However,the specific mechanism still needs to be further explored.Recent studies have found that the opening of the mitoKATP channel can regulate mitochondrial autophagy,and the initiation of miRNA-DNA methylation plays a regulatory role in inducing cell autophagy.The applicant research team previously found that Qishen Yiqi Dropping Pills could significantly improve myocardial ischemia by mediating MitokATP channels to regulate mitochondrial autophagy.,and animal experiments have confirmed that miR-155 plays a significant role in the aspect of autophagy regulates,inflammatory reaction and Vascular smooth muscle cell migration.Therefore,the applicant innovatively proposed that Qishen Yiqi Dropping Pills can regulate miRNA155-DNA methylation to mediate the opening of mitoKATP,thereby regulating mitochondrial autophagy and improving myocardial ischemia.In this paper,the association between mitochondrial autophagy and oxidative stress injury after myocardial ischemia was described,and the possible mechanism of Qisen Yiqi dropping pills regulating mitochondrial autophagy by regulating miRNA155-DNA methylation to mediate MitokATP to improve myocardial ischemia reperfusion injury was discussed,so as to provide theoretical ideas for related research.
文摘With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.
