BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
Objective:To confirm the therapeutic efficacy of the ginkgo biloba extract EGb761 on ischemic stroke and elucidate its underlying mechanism.Methods:Male Sprague-Dawley rats were divided into three groups:sham,model,an...Objective:To confirm the therapeutic efficacy of the ginkgo biloba extract EGb761 on ischemic stroke and elucidate its underlying mechanism.Methods:Male Sprague-Dawley rats were divided into three groups:sham,model,and EGb761(ginkgo biloba extract).Ischemic stroke was then simulated in rats via embolic middle cerebral artery occlusion surgery,with the extract administered half an hour before surgery.Neurological deficit scores,infarct volume,cerebral edema rate,and inflammatory factors served as the primary metrics for drug efficacy.Serum metabolites were analyzed using 1H-nuclear magnetic resonance to elucidate the operative mechanism.Results:Treatment with the ginkgo biloba extract EGb761 significantly ameliorated the neurological deficit scores(P=.0343),diminished the cerebral infarct volume(P=.0001)and cerebral edema rate(P=.0030),and alleviated neuroinflammation(all P<.05)in middle cerebral artery occlusion rats.In addition,it significantly altered the contents of various metabolites,such as 2-hydroxybutyrate,isoleucine,isopropanol,isobutyric acid,N6-acetyllysine,glutamate,glutamine,methionine,and N,Ndimethylglycine(all P<.05).Enrichment analysis of the differential metabolites indicated that EGb761 may be involved in the regulation of amino acid metabolism,betaine metabolism,glucose-alanine cycle,Warburg effect,and urea cycle.Conclusion:The ginkgo biloba extract EGb761 demonstrates anti-ischemic stroke effect on ischemic stroke model rats by regulating amino acids and amino acid derivatives,such as isoleucine,N6-acetyllysine,glutamate,methionine,and N,N-dimethylglycine.展开更多
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
基金supported by the Youth Science Fund Project of the National Natural Science Foundation of China(82104440).
文摘Objective:To confirm the therapeutic efficacy of the ginkgo biloba extract EGb761 on ischemic stroke and elucidate its underlying mechanism.Methods:Male Sprague-Dawley rats were divided into three groups:sham,model,and EGb761(ginkgo biloba extract).Ischemic stroke was then simulated in rats via embolic middle cerebral artery occlusion surgery,with the extract administered half an hour before surgery.Neurological deficit scores,infarct volume,cerebral edema rate,and inflammatory factors served as the primary metrics for drug efficacy.Serum metabolites were analyzed using 1H-nuclear magnetic resonance to elucidate the operative mechanism.Results:Treatment with the ginkgo biloba extract EGb761 significantly ameliorated the neurological deficit scores(P=.0343),diminished the cerebral infarct volume(P=.0001)and cerebral edema rate(P=.0030),and alleviated neuroinflammation(all P<.05)in middle cerebral artery occlusion rats.In addition,it significantly altered the contents of various metabolites,such as 2-hydroxybutyrate,isoleucine,isopropanol,isobutyric acid,N6-acetyllysine,glutamate,glutamine,methionine,and N,Ndimethylglycine(all P<.05).Enrichment analysis of the differential metabolites indicated that EGb761 may be involved in the regulation of amino acid metabolism,betaine metabolism,glucose-alanine cycle,Warburg effect,and urea cycle.Conclusion:The ginkgo biloba extract EGb761 demonstrates anti-ischemic stroke effect on ischemic stroke model rats by regulating amino acids and amino acid derivatives,such as isoleucine,N6-acetyllysine,glutamate,methionine,and N,N-dimethylglycine.
