[Objectives]This study aimed to investigate the effects of lignans from seeds of Herpetospermum caudigerum Wall.(SHC)on expression of TGF-β/Smads in liver tissue of hepatic alcohol-injuried rats,and to explore its pr...[Objectives]This study aimed to investigate the effects of lignans from seeds of Herpetospermum caudigerum Wall.(SHC)on expression of TGF-β/Smads in liver tissue of hepatic alcohol-injuried rats,and to explore its protective mechanism.[Methods]A total of 60 SD rats were randomly divided into six groups.The rats in all the groups except those in the normal group were given with white spirit by gavage for 8 weeks to establish alcoholic liver injury models.After rat models were established successfully,they were administered intragastrically with 400,200 and 100 mg/kg of lignans,respectively.The rats in the normal group were administered intragastrically with 50 mg/kg of silymarin.The administration lasted for 8 weeks,once a day.The changes in the general state,liver tissue pathology and collagen deposition of the rats were observed.The expression of TGF-β,TGF-β1 receptor 1(TβR-I),TGF-β1 receptor 2(TβR-II),Smad2/p-Smad2 and Smad3/p-Smad3 in the hepatic tissue was detected.[Results]The expression levels of TGF-β1,Smad2,p-Smad2,and p-Smad3 significantly declined,and the expression levels of TβR-I,TβR-II and Smad3 did not change significantly in the liver tissue of rats in the lignans groups and the expression levels of TGF-β,Smad2,and p-Smad3 significantly declined.Meanwhile,the expression levels of TβR-I,TβR-II,p-Smad2 and Smad3 did not change significantly in the silymarin group.[Conclusions]The lignans from SHC have significant intervention effects on alcoholic livery injury.The mechanism may be related to the inhibition of hepatic stellate cell(HSC)activation,TGF-βsecretion and p-Smad2,p-Smad3 expression in the signaling pathway.展开更多
Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure tre...Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure treatment. Methods: Healthy male Sprague-Dawley rats were allocated into three groups: Sham group, Model group, and electroacupuncture (Model + EA) group, with each group comprising 8 rats. The model underwent a procedure involving the ligation of the left anterior descending coronary artery to induce a model of heart failure. The Model + EA group was used for 7 consecutive days for electroacupuncture of bilateral Shenmen (HT7) and Tongli (HT5), once a day for 30 min each time. Left ventricular parameters in rats were assessed using a small-animal ultrasound machine to analyze changes in left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. Serum interleukin-1β (IL-1β), cardiac troponin (cTn), and N-terminal brain natriuretic peptide precursor levels were measured using ELISA. Histopathological changes in rat myocardium were observed through HE staining, while collagen deposition in rat myocardial tissue was assessed using the Masson staining method. Picro sirius red staining, immunohistochemical staining, and RT-qPCR were utilized to distinguish between the various types of collagen deposition. The expression level of TGF-β1 and SMAD2/3/4/7 mRNA in rat myocardial tissues was determined using RT-qPCR. Additionally, western blot analysis was conducted to assess the protein expression levels of TGF-β1, SMAD3/7, and p-SMAD3 in rat myocardial tissues. Results: Compared with the Sham group, the left ventricular ejection fraction and left ventricular fractional shortening values of the Model group were significantly decreased (P < 0.01);the left ventricular end-diastolic volume and left ventricular end-systolic volume values were remarkably increased (P < 0.01);serum N-terminal brain natriuretic peptide precursor content was increased (P < 0.01);serum IL-1β and cTn levels were increased (P < 0.01);myocardial collagen volume fraction were increased (P < 0.01);and those of the expression of TGF-β1 and SMAD2/3/4 mRNA was increased (P < 0.01);the expression of SMAD7 mRNA was decreased (P < 0.01);the protein expression levels of TGF-β1, SMAD3, and p-Smad3 were increased (P < 0.01);the protein expression level of SMAD7 was decreased (P < 0.01) in the Model group. Compared to the Model group, the expression levels of the proteins TGF-β1, SMAD3, and p-Smad3 in myocardial tissue were found to be decreased (P < 0.01), and the expression level of the protein SMAD7 was found to be increased (P < 0.01) in the Model + EA group;the collagen volume fraction and deposition of type Ⅰ /Ⅲ collagen were decreased (P < 0.01) in the Model + EA group. Conclusion: Electroacupuncture alleviates myocardial fibrosis in rats with heart failure, and this effect is likely due to attributed to the modulation of the TGF-β1/Smads signaling pathway, which helps reduce collagen deposition in the extracellular matrix.展开更多
Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastr...Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored.Material and Methods:Initially,EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines.Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45,and downregulation in EBVpositive cells(SUN-719).The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation,migration,and glycolytic processes,with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-βinhibitor.Results:EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells,while its target gene SMAD4 demonstrates downregulated expression.Upregulation of it can promote the proliferation and migration of gastric cancer cells.Additionally,We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer cells.Inhibition of the TGF-β/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells,concomitant with a diminished glycolytic capacity.Conclusion:In this study,we found that EBV-miRNA-BART6-5p can target SMAD4,effectively increasing glycolysis in gastric cancer cells by regulating the TGF-β/SMAD4 signaling pathway,thereby enhancing the proliferation and metastasis of gastric cancer cells.Our findings may offer new insights into the metabolic aspects of gastric cancer.展开更多
基金Graduates'Innovation Project of Southwest Minzu University(CX2016SZ032)National Natural Science Foundation of China(81274168,81573563)Scientific Research Project of Sichuan Provincial Administration of TCM(2016C062).
文摘[Objectives]This study aimed to investigate the effects of lignans from seeds of Herpetospermum caudigerum Wall.(SHC)on expression of TGF-β/Smads in liver tissue of hepatic alcohol-injuried rats,and to explore its protective mechanism.[Methods]A total of 60 SD rats were randomly divided into six groups.The rats in all the groups except those in the normal group were given with white spirit by gavage for 8 weeks to establish alcoholic liver injury models.After rat models were established successfully,they were administered intragastrically with 400,200 and 100 mg/kg of lignans,respectively.The rats in the normal group were administered intragastrically with 50 mg/kg of silymarin.The administration lasted for 8 weeks,once a day.The changes in the general state,liver tissue pathology and collagen deposition of the rats were observed.The expression of TGF-β,TGF-β1 receptor 1(TβR-I),TGF-β1 receptor 2(TβR-II),Smad2/p-Smad2 and Smad3/p-Smad3 in the hepatic tissue was detected.[Results]The expression levels of TGF-β1,Smad2,p-Smad2,and p-Smad3 significantly declined,and the expression levels of TβR-I,TβR-II and Smad3 did not change significantly in the liver tissue of rats in the lignans groups and the expression levels of TGF-β,Smad2,and p-Smad3 significantly declined.Meanwhile,the expression levels of TβR-I,TβR-II,p-Smad2 and Smad3 did not change significantly in the silymarin group.[Conclusions]The lignans from SHC have significant intervention effects on alcoholic livery injury.The mechanism may be related to the inhibition of hepatic stellate cell(HSC)activation,TGF-βsecretion and p-Smad2,p-Smad3 expression in the signaling pathway.
基金the China’s National Key Research and Development Program Projects(No.2022YFC3500500 and No.2022YFC3500502).
文摘Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure treatment. Methods: Healthy male Sprague-Dawley rats were allocated into three groups: Sham group, Model group, and electroacupuncture (Model + EA) group, with each group comprising 8 rats. The model underwent a procedure involving the ligation of the left anterior descending coronary artery to induce a model of heart failure. The Model + EA group was used for 7 consecutive days for electroacupuncture of bilateral Shenmen (HT7) and Tongli (HT5), once a day for 30 min each time. Left ventricular parameters in rats were assessed using a small-animal ultrasound machine to analyze changes in left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. Serum interleukin-1β (IL-1β), cardiac troponin (cTn), and N-terminal brain natriuretic peptide precursor levels were measured using ELISA. Histopathological changes in rat myocardium were observed through HE staining, while collagen deposition in rat myocardial tissue was assessed using the Masson staining method. Picro sirius red staining, immunohistochemical staining, and RT-qPCR were utilized to distinguish between the various types of collagen deposition. The expression level of TGF-β1 and SMAD2/3/4/7 mRNA in rat myocardial tissues was determined using RT-qPCR. Additionally, western blot analysis was conducted to assess the protein expression levels of TGF-β1, SMAD3/7, and p-SMAD3 in rat myocardial tissues. Results: Compared with the Sham group, the left ventricular ejection fraction and left ventricular fractional shortening values of the Model group were significantly decreased (P < 0.01);the left ventricular end-diastolic volume and left ventricular end-systolic volume values were remarkably increased (P < 0.01);serum N-terminal brain natriuretic peptide precursor content was increased (P < 0.01);serum IL-1β and cTn levels were increased (P < 0.01);myocardial collagen volume fraction were increased (P < 0.01);and those of the expression of TGF-β1 and SMAD2/3/4 mRNA was increased (P < 0.01);the expression of SMAD7 mRNA was decreased (P < 0.01);the protein expression levels of TGF-β1, SMAD3, and p-Smad3 were increased (P < 0.01);the protein expression level of SMAD7 was decreased (P < 0.01) in the Model group. Compared to the Model group, the expression levels of the proteins TGF-β1, SMAD3, and p-Smad3 in myocardial tissue were found to be decreased (P < 0.01), and the expression level of the protein SMAD7 was found to be increased (P < 0.01) in the Model + EA group;the collagen volume fraction and deposition of type Ⅰ /Ⅲ collagen were decreased (P < 0.01) in the Model + EA group. Conclusion: Electroacupuncture alleviates myocardial fibrosis in rats with heart failure, and this effect is likely due to attributed to the modulation of the TGF-β1/Smads signaling pathway, which helps reduce collagen deposition in the extracellular matrix.
基金supported by National Health Commission Key Laboratory of Gastrointestinal Tumour Diagnosis and Treatment 2022 Master/Postdoctoral Fund Project(NHCDP2022005)Gansu Provincial Science and Technology Department Joint Scientific Research Fund Project(23JRRA1545)+1 种基金Gansu Provincial Hospital Intra-Hospital Research Fund Project(22GSYYD-37)International Co-Operation Project of Gansu Provincial Science and Technology Department(No.20YF8WA096).
文摘Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored.Material and Methods:Initially,EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines.Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45,and downregulation in EBVpositive cells(SUN-719).The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation,migration,and glycolytic processes,with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-βinhibitor.Results:EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells,while its target gene SMAD4 demonstrates downregulated expression.Upregulation of it can promote the proliferation and migration of gastric cancer cells.Additionally,We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer cells.Inhibition of the TGF-β/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells,concomitant with a diminished glycolytic capacity.Conclusion:In this study,we found that EBV-miRNA-BART6-5p can target SMAD4,effectively increasing glycolysis in gastric cancer cells by regulating the TGF-β/SMAD4 signaling pathway,thereby enhancing the proliferation and metastasis of gastric cancer cells.Our findings may offer new insights into the metabolic aspects of gastric cancer.
