Objective： To investigate the effect of berberine, one of the main alkaloids of Rhizoma coptidis, on myocardial morphology and the expressions of cyclin-dependent kinase 9 （Cdk9） and cyclin T1 protein in the myocar...Objective： To investigate the effect of berberine, one of the main alkaloids of Rhizoma coptidis, on myocardial morphology and the expressions of cyclin-dependent kinase 9 （Cdk9） and cyclin T1 protein in the myocardium of type 2 diabetic rats. Methods： Type 2 diabetes mellitus rats were induced by an injection of 35 mg/kg streptozotocin （STZ） and a high-carbohydrate/high-fat diet for 16 weeks. Diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg/kg）, fenofibrate （100 mg/kg） and rosiglitazone （4 mg/kg） for another 16 weeks, respectively. The myocardium structure was observed with hematoxylin ＆ eosin （H＆E） staining and Cdk9 and cyclin T1 protein expressions were detected by immunohistochemistry. Results： Middle-dose, high-dose berberine improved myocardial hypertrophy and interstitial fibrosis of diabetic rats. Cdk9 and cyclin T1 protein were significantly lower in diabetic myocardium than in control one （P〈0.01）, and middle-dose, high-dose berberine and fenofibrate obviously increased both Cdk9 and cyclin T1 expression to near control level （P〈0.01）. Conclusion： Berberine modulates Cdk9 and cyclin T1 protein expression in diabetic myocardium which may contribute to ameliorate myocardium damage.展开更多
The protein encoded by HSRG1(HSV-1 stimulation-related gene 1) is a virally induced protein expressed in HSV-1-infected cells.We have already reported that HSRG1 is capable of interacting with transcriptional regulato...The protein encoded by HSRG1(HSV-1 stimulation-related gene 1) is a virally induced protein expressed in HSV-1-infected cells.We have already reported that HSRG1 is capable of interacting with transcriptional regulator proteins.To further analyze the effects of HSRG1 on the regulation of viral gene transcription,we expressed the HSRG1 protein in transfected cells and found that it postpones the proliferation of HSV-1.CAT(chloramphenicol acetyltransferase) assays also revealed that HSRG1 reduces transcription from HSV-1 promoters.Yeast two-hybrid and immunoprecipitation assays indicated that HSRG1 interacts with Cyclin T2,the regulatory subunit of P-TEFb,which is required for transcription elongation by RNA Pol II(RNAP II) ,and that amino acid residues 1-420 in Cyclin T2 are important for binding with HSRG1.Fluorescence assays suggested that the cellular localizations of those two proteins are influenced by their interaction.Further analyses with CAT assays revealed that HSRG1 inhibits the transcriptional activation by Cyclin T2 of viral promoters.Our results suggested that the inhibitory effects of HSRG1 on viral replication and proliferation are probably induced by its binding to Cyclin T2.Therefore,it is likely that HSRG1 inhibits viral gene transcriptional elongation by interacting with Cyclin T2.展开更多
Cellular senescence is a form of permanent cell cycle arrest that can be triggered by a variety of cell-intrinsic and extrinsic stimuli, including telomere shortening,DNA damage, oxidative stress, and exposure to chem...Cellular senescence is a form of permanent cell cycle arrest that can be triggered by a variety of cell-intrinsic and extrinsic stimuli, including telomere shortening,DNA damage, oxidative stress, and exposure to chemotherapeutic agents and ionizing radiation. Although the induction of apoptotic cell death is a desirable outcome in cancer therapy, mutations and/or deficiencies in the apoptotic signaling pathways have been frequently identified in many human cancer types,suggesting the importance of alternative apoptosis-independent therapeutic approaches for cancer treatment. A growing body of evidence has documented that senescence induction in tumor cells is a frequent response to many anticancer modalities including cyclin-dependent kinases 4/6 small molecule inhibitor-based targeted therapeutics and T helper-1 cytokine-mediated immunotherapy. This review discusses the recent advances and clinical relevance of therapy-induced senescence in cancer treatment.展开更多
文摘Objective： To investigate the effect of berberine, one of the main alkaloids of Rhizoma coptidis, on myocardial morphology and the expressions of cyclin-dependent kinase 9 （Cdk9） and cyclin T1 protein in the myocardium of type 2 diabetic rats. Methods： Type 2 diabetes mellitus rats were induced by an injection of 35 mg/kg streptozotocin （STZ） and a high-carbohydrate/high-fat diet for 16 weeks. Diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg/kg）, fenofibrate （100 mg/kg） and rosiglitazone （4 mg/kg） for another 16 weeks, respectively. The myocardium structure was observed with hematoxylin ＆ eosin （H＆E） staining and Cdk9 and cyclin T1 protein expressions were detected by immunohistochemistry. Results： Middle-dose, high-dose berberine improved myocardial hypertrophy and interstitial fibrosis of diabetic rats. Cdk9 and cyclin T1 protein were significantly lower in diabetic myocardium than in control one （P〈0.01）, and middle-dose, high-dose berberine and fenofibrate obviously increased both Cdk9 and cyclin T1 expression to near control level （P〈0.01）. Conclusion： Berberine modulates Cdk9 and cyclin T1 protein expression in diabetic myocardium which may contribute to ameliorate myocardium damage.
基金supported by the National Natural Science Foundation of China(Grant Nos.30700028,30670094)the Doctoral Fund of Ministry of Education of China(Grant No.0060023008)
文摘The protein encoded by HSRG1(HSV-1 stimulation-related gene 1) is a virally induced protein expressed in HSV-1-infected cells.We have already reported that HSRG1 is capable of interacting with transcriptional regulator proteins.To further analyze the effects of HSRG1 on the regulation of viral gene transcription,we expressed the HSRG1 protein in transfected cells and found that it postpones the proliferation of HSV-1.CAT(chloramphenicol acetyltransferase) assays also revealed that HSRG1 reduces transcription from HSV-1 promoters.Yeast two-hybrid and immunoprecipitation assays indicated that HSRG1 interacts with Cyclin T2,the regulatory subunit of P-TEFb,which is required for transcription elongation by RNA Pol II(RNAP II) ,and that amino acid residues 1-420 in Cyclin T2 are important for binding with HSRG1.Fluorescence assays suggested that the cellular localizations of those two proteins are influenced by their interaction.Further analyses with CAT assays revealed that HSRG1 inhibits the transcriptional activation by Cyclin T2 of viral promoters.Our results suggested that the inhibitory effects of HSRG1 on viral replication and proliferation are probably induced by its binding to Cyclin T2.Therefore,it is likely that HSRG1 inhibits viral gene transcriptional elongation by interacting with Cyclin T2.
文摘Cellular senescence is a form of permanent cell cycle arrest that can be triggered by a variety of cell-intrinsic and extrinsic stimuli, including telomere shortening,DNA damage, oxidative stress, and exposure to chemotherapeutic agents and ionizing radiation. Although the induction of apoptotic cell death is a desirable outcome in cancer therapy, mutations and/or deficiencies in the apoptotic signaling pathways have been frequently identified in many human cancer types,suggesting the importance of alternative apoptosis-independent therapeutic approaches for cancer treatment. A growing body of evidence has documented that senescence induction in tumor cells is a frequent response to many anticancer modalities including cyclin-dependent kinases 4/6 small molecule inhibitor-based targeted therapeutics and T helper-1 cytokine-mediated immunotherapy. This review discusses the recent advances and clinical relevance of therapy-induced senescence in cancer treatment.
