Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypot...Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase Ⅶ into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10(PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3(NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.展开更多
Objective:To determine the anti-proliferative activity of Abrus precatorius(A.precatorius)leaf extracts and their effect on cell death.Methods:A.precatorius leaves were extracted successively with hexane,ethyl acetate...Objective:To determine the anti-proliferative activity of Abrus precatorius(A.precatorius)leaf extracts and their effect on cell death.Methods:A.precatorius leaves were extracted successively with hexane,ethyl acetate and methanol by Soxhlet extraction.Aqueous extract was prepared by decoction at 50 ℃.Extracts of A.precatorius leaves were used to treat selected cancer and normal cell lines for72 h.Furthermore,3-(4,5-dimethyl thiazol-2-yl)2,5-diphenyl tetrazolium bromide assay was performed to determine cell viability.Analysis of cell cycle arrest,apoptosis assay and apoptosis protein expressions were determined by flow cytometry.Results:Methanolic extract of A.precatorius leaves showed the lowest IC50 on MDA-MB-231 cells at(26.40±5.40)μg/mL.Flow cytometry analysis revealed that cell arrest occurred at G0/G1 phase and the apoptosis assay showed the occurrence of early apoptosis at 48 h in MDAMB-231 cells treated with methanolic extract of A.precatorius leaves.Methanolic extract of A.precatorius leaves induced apoptosis by upregulation of Bax,p53 and caspase-3 and downregulation of Bcl-2.Conclusions:Methanolic extract of A precatorius leaves promotes MDA-MB-231 cell death by inducing cell cycle arrest and apoptosis possibly via the mitochondrial-related pathway.展开更多
Objective： To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods： Light microscopy was used to determine the effects of amlodipine on cell morp...Objective： To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods： Light microscopy was used to determine the effects of amlodipine on cell morphology; Flow cytometry was used to quantitate cells undergoing apoptosis; the expression of a cell cycle-related protein, proliferating cell nuclear antigen （PCNA） and an antiapoptosis protein, Bcl-2 were assessed by immunocytochemistry. Results： Amlodipine concentration of 8.25umol/L （1/2 of ICs0） affected the morphology, decreased the expression of PCNA and Bcl-2 and induced apoptosis of human breast carcinoma MDA-MB-231 cells. Conclusion： The effect of amlodipine on the antiproliferation of human breast carcinoma MDA-MB-231 cells is related to inducement of apoptosis, and the decrease of the expression of Bcl-2 and PCNA may be the possible mechanism for proliferation inhibitory and inducement of apoptosis.展开更多
OBJECTIVE To investigate the anti-proliferative effect of rosiglitazone and its relationship to peroxisome proliferator-activated receptor γ （PPARγ） in human breast cancer cell line MDA-MB-231 and evaluate the pot...OBJECTIVE To investigate the anti-proliferative effect of rosiglitazone and its relationship to peroxisome proliferator-activated receptor γ （PPARγ） in human breast cancer cell line MDA-MB-231 and evaluate the potential application value of rosiglitazone for breast cancer therapy. METHODS The cytostatic effect of rosiglitazone on MDA- MB-231 cells was measured by the MTT assay. Cell-cycle kinetics was assessed by flow cytometry. Apoptotic cells were determined by the TUNEL assay. MDA-MB-231 cells were treated with rosiglitazone or in combination with the PPARy antagonist GW9662 to investigate the effect of rosiglitazone on cell proliferation and its relationship to PPARγ. RESULTS The results showed that rosiglitazone could inhibit growth of MDA-MB-231 cells in a dose- and time-dependent manner with an IC50 value of 5.2 μmol/L at 24 h after the drug was added into the culture. Cell cycle analysis showed that the percentage of G0/G1 phase cells increased, S phase cells decreased, and cells were arrested in G1 phase with increasing concentrations of rosiglitazone. Detectable signs of apoptotic cell death caused by rosiglitazone occurred at a concentration of 100 μmol/L and the apoptotic rate was （18 ± 3）%. PPARγ selective antagonist GW9662 could partially reverse the inhibitory effect of rosiglitazone on proliferation of MDA-MB-231 cells. CONCLUSION It was concluded that rosiglitazone can inhibit growth of MDA-MB-231 cells via PPARy activation and a high concentration of rosiglitazone can also induce MDA-MB-231 cell apoptosis. These results suggest that PPARy represents a putative molecular target for chemopreventive therapy and rosiglitazone may be effective in the treatment of breast cancer.展开更多
目的探究视黄酸相关孤儿受体(RORγt)白细胞介素23(IL-23)通路调节辅助性T细胞17(Th17)在老年盐敏感性高血压发病中的作用。方法对内蒙古自治区的村民进行调查,2021年1月至2022年1月选取289例老年高血压患者作为研究对象,采用Sullivan...目的探究视黄酸相关孤儿受体(RORγt)白细胞介素23(IL-23)通路调节辅助性T细胞17(Th17)在老年盐敏感性高血压发病中的作用。方法对内蒙古自治区的村民进行调查,2021年1月至2022年1月选取289例老年高血压患者作为研究对象,采用Sullivan盐负荷试验将患者进行分组,盐敏感高血压患者103例作为研究组,非盐敏感高血压患者186例作为对照组,给予慢性盐负荷试验。结果研究组收缩压、舒张压、MAP、心率在D10、D17均显著高于对照组(P<0.01)。2组尿量、尿钠、尿钾、尿肌酐水平在基线D3比较无显著差异(P>0.05),D10与对照组比较,研究组尿钠[(315.32±57.21)mmol/24 h vs(226.64±58.53)mmol/24 h,P=0.000]、尿肌酐[(12.46±1.64)mmol/24 h vs(10.12±1.17)mmol/24 h,P=0.000]显著增高。2组Th17比例、IL-17A水平在D4、D5、D10逐渐上升,在D17下降,且研究组Th17比例、IL-17A水平在D4、D5、D10、D17均显著高于对照组(P<0.01)。结论Th17参与了盐敏感性高血压的发生,RORγt-IL-23受体信号通路可诱导Th17细胞分化。展开更多
BACKGROUND The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory resp...BACKGROUND The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory response, improve immune dysfunction, and prevent enterogenic infection in critically ill patients;however, the precise mechanisms remain unclear. Considering the important roles of Th17 and Treg lymphocytes in the development of inflammatory and infectious diseases, we hypothesized that EEN could improve the immune dysfunction in sepsis by maintaining a balanced Th17/Treg cell ratio and by regulating the IL- 23/IL-17 axis. AIM To investigate the effects of EEN on the Th17/Treg cell ratios and the IL-23/IL-17 axis in septic patients. METHODS In this prospective clinical trial, patients were randomly divided into an EEN or delayed enteral nutrition (DEN) group. Enteral feeding was started within 48 h in the EEN group, whereas enteral feeding was started on the 4th day in the DEN group. The Th17 and Treg cell percentages and the interleukin levels were tested on days 1, 3, and 7 after admission. The clinical severity and outcome variables were also recorded. RESULTS Fifty-three patients were enrolled in this trial from October 2017 to June 2018. The Th17 cell percentages, Th17/Treg cell ratios, IL-17, IL-23, and IL-6 levels of the EEN group were lower than those of the DEN group on the 7th day after admission (P < 0.05). The duration of mechanical ventilation and of the intensive care unit stay of the EEN group were shorter than those of the DEN group (P <0.05). However, no difference in the 28-d mortality was found between the two groups (P = 0.728). CONCLUSION EEN could regulate the imbalance of Th17/Treg cell ratios and suppress the IL- 23/IL-17 axis during sepsis. Moreover, EEN could reduce the clinical severity of sepsis but did not reduce the 28-d mortality of septic patients.展开更多
Objective: The present study aimed to investigate the molecular events in alisol B 23-acetate(ABA) cytotoxic activity against a liver cancer cell line.Methods: First, we employed a quantitative proteomics approach bas...Objective: The present study aimed to investigate the molecular events in alisol B 23-acetate(ABA) cytotoxic activity against a liver cancer cell line.Methods: First, we employed a quantitative proteomics approach based on stable isotope labeling by amino acids in cell culture(SILAC) to identify the different proteins expressed in HepG2 liver cancer cells upon exposure to ABA. Next, bioinformatics analyses through DAVID and STRING on-line tools were used to predict the pathways involved. Finally, we applied functional validation including cell cycle analysis and Western blotting for apoptosis and mTOR pathway-related proteins to confirm the bioinformatics predictions.Results: We identified 330 different proteins with the SILAC-based quantitative proteomics approach. The bioinformatics analysis and the functional validation revealed that the mTOR pathway, ribosome biogenesis, cell cycle, and apoptosis pathways were differentially regulated by ABA. G1 cell cycle arrest, apoptosis and mTOR inhibition were confirmed.Conclusions: ABA, a potential mTOR inhibitor, induces the disruption of ribosomal biogenesis. It also affects the mTOR-MRP axis to cause G1 cell cycle arrest and finally leads to cancer cell apoptosis.展开更多
LM23 is a gene specifically expressed in the testis of Rattus norvegicus, as previously reported by our laboratory. The aim of the study is to further investigate the biological function of LM23. Several bioinformatic...LM23 is a gene specifically expressed in the testis of Rattus norvegicus, as previously reported by our laboratory. The aim of the study is to further investigate the biological function of LM23. Several bioinformatic tools were utilized, including PROSITE and BLAST. To determine the subcellullar localization of LM23, a polyclonal antibody specific for LM23 was generated via the immunization of rabbits. The LM23gene was cloned from rat testis tissue, and LM23 protein was expressed in Escherichia co/i. The biological function of LM23 was analyzed with microarray analysis and immunohistochemistry, using a rat model of LM23 gene knockdown. The results suggested that LM23 belongs to the Speedy/Ringo family. LM23 regulated the GI/S and G2/M transitions of the cell cycle during spermatogenesis. Downregulation of the LM23gene during spermatogenesis could lead to the activation of both the Fas-FasL pathway and the mitochondrial pathway. These novel findings indicate that LM23 has a diverse array of functions that are important in both the life and death of the spermatogenic cell.展开更多
Age-related osteoporosis is associated with the reduced capacity of bone marrow mesenchymal stem cells （BMSCs） to differentiate into osteoblasts instead of adipocytes. However, the molecular mechanisms that decide t...Age-related osteoporosis is associated with the reduced capacity of bone marrow mesenchymal stem cells （BMSCs） to differentiate into osteoblasts instead of adipocytes. However, the molecular mechanisms that decide the fate of BMSCs remain unclear. In our study, microRNA-23a, and microRNA-23b （miR-23a/b） were found to be markedly downregulated in BMSCs of aged mice and humans. The overexpression of miR-23a/b in BMSCs promoted osteogenic differentiation, whereas the inhibition of miR-23a/b increased adipogenic differentiation. Transmembrane protein 64 （Tmem64）, which has expression levels inversely related to those of miR-23a/b in aged and young mice, was identified as a major target of miR-23a/b during BMSC differentiation. In conclusion, our study suggests that miR-23a/b has a critical role in the regulation of mesenchymal lineage differentiation through the suppression of Tmem64.展开更多
Protein Rad23, a nucleotide excision repair factor, mainly involves in repairing the DNA damage from environment, such as UV light. The function of Rad23 protein involved in DNA damage repair from many environmental f...Protein Rad23, a nucleotide excision repair factor, mainly involves in repairing the DNA damage from environment, such as UV light. The function of Rad23 protein involved in DNA damage repair from many environmental factors has been studied extensively, but it is not clear from ultraviolet irradiation. To further investigate the photo-protective function of Rad23 protein on HeLa cells damaged from UV light irradiation, firstly, HeLa cells were irradiated by UV light and incubated with the fusion protein of pCold-Rad23, then the cell viability and apoptosis rate were detected by MTT and Hoechst33342/Pl fluorescent staining, respectively. The results show that the recombinant Rad23 protein can protect the HeLa cells from UV irradiation, and inhibit the apoptosis of HeLa cell by UV irradiation.展开更多
[Objectives]To investigate the mechanism of miR-23a in the proliferation of human tongue squamous cell carcinoma cells.[Methods]Clinical tissue samples of tongue squamous cell carcinoma were collected and Tca8113 and ...[Objectives]To investigate the mechanism of miR-23a in the proliferation of human tongue squamous cell carcinoma cells.[Methods]Clinical tissue samples of tongue squamous cell carcinoma were collected and Tca8113 and CAL27 were cultured.Real-time quantitative PCR was performed to detect the expressions of miR-23a and PPP2R5E in clinical tissue samples of tongue squamous cell carcinoma.MTT assay,colony formation assay and growth curve assay were used to detect the effect of miR-23a and PPP2R5E on the proliferation of human tongue squamous carcinoma cell.Luciferase reporter assay verified the regulatory relationship between miR-23a and PPP2R5E.[Results]The expression of miR-23a in tongue squamous cell carcinoma was significantly up-regulated(P<0.01).miR-23a promoted the proliferation of tongue squamous cell carcinoma cells.Bioinformatics prediction and luciferin reporting experiments showed that PPP2R5E was a direct target gene of miR-23a.The expression of PPP2R5E was decreased in tongue squamous cell carcinoma.PPP2R5E inhibited the proliferation of tongue squamous cell carcinoma cells.Overexpression of PPP2R5E can reverse the proliferation promoting effect of miR-23a on tongue squamous cell carcinoma cells.[Conclusions]miR-23a can promote the proliferation of tongue squamous cell carcinoma cells through PPP2R5E and miR-23a plays an oncogene role in the occurrence and development of tongue squamous cell carcinoma.展开更多
基金supported by the National Natural Science Foundation of China,No.81571120(to ZYH).
文摘Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase Ⅶ into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10(PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3(NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.
基金funded by the Universiti Sains Malaysia Short Term Grant(304/PPSP/61313046)
文摘Objective:To determine the anti-proliferative activity of Abrus precatorius(A.precatorius)leaf extracts and their effect on cell death.Methods:A.precatorius leaves were extracted successively with hexane,ethyl acetate and methanol by Soxhlet extraction.Aqueous extract was prepared by decoction at 50 ℃.Extracts of A.precatorius leaves were used to treat selected cancer and normal cell lines for72 h.Furthermore,3-(4,5-dimethyl thiazol-2-yl)2,5-diphenyl tetrazolium bromide assay was performed to determine cell viability.Analysis of cell cycle arrest,apoptosis assay and apoptosis protein expressions were determined by flow cytometry.Results:Methanolic extract of A.precatorius leaves showed the lowest IC50 on MDA-MB-231 cells at(26.40±5.40)μg/mL.Flow cytometry analysis revealed that cell arrest occurred at G0/G1 phase and the apoptosis assay showed the occurrence of early apoptosis at 48 h in MDAMB-231 cells treated with methanolic extract of A.precatorius leaves.Methanolic extract of A.precatorius leaves induced apoptosis by upregulation of Bax,p53 and caspase-3 and downregulation of Bcl-2.Conclusions:Methanolic extract of A precatorius leaves promotes MDA-MB-231 cell death by inducing cell cycle arrest and apoptosis possibly via the mitochondrial-related pathway.
文摘Objective： To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods： Light microscopy was used to determine the effects of amlodipine on cell morphology; Flow cytometry was used to quantitate cells undergoing apoptosis; the expression of a cell cycle-related protein, proliferating cell nuclear antigen （PCNA） and an antiapoptosis protein, Bcl-2 were assessed by immunocytochemistry. Results： Amlodipine concentration of 8.25umol/L （1/2 of ICs0） affected the morphology, decreased the expression of PCNA and Bcl-2 and induced apoptosis of human breast carcinoma MDA-MB-231 cells. Conclusion： The effect of amlodipine on the antiproliferation of human breast carcinoma MDA-MB-231 cells is related to inducement of apoptosis, and the decrease of the expression of Bcl-2 and PCNA may be the possible mechanism for proliferation inhibitory and inducement of apoptosis.
文摘OBJECTIVE To investigate the anti-proliferative effect of rosiglitazone and its relationship to peroxisome proliferator-activated receptor γ （PPARγ） in human breast cancer cell line MDA-MB-231 and evaluate the potential application value of rosiglitazone for breast cancer therapy. METHODS The cytostatic effect of rosiglitazone on MDA- MB-231 cells was measured by the MTT assay. Cell-cycle kinetics was assessed by flow cytometry. Apoptotic cells were determined by the TUNEL assay. MDA-MB-231 cells were treated with rosiglitazone or in combination with the PPARy antagonist GW9662 to investigate the effect of rosiglitazone on cell proliferation and its relationship to PPARγ. RESULTS The results showed that rosiglitazone could inhibit growth of MDA-MB-231 cells in a dose- and time-dependent manner with an IC50 value of 5.2 μmol/L at 24 h after the drug was added into the culture. Cell cycle analysis showed that the percentage of G0/G1 phase cells increased, S phase cells decreased, and cells were arrested in G1 phase with increasing concentrations of rosiglitazone. Detectable signs of apoptotic cell death caused by rosiglitazone occurred at a concentration of 100 μmol/L and the apoptotic rate was （18 ± 3）%. PPARγ selective antagonist GW9662 could partially reverse the inhibitory effect of rosiglitazone on proliferation of MDA-MB-231 cells. CONCLUSION It was concluded that rosiglitazone can inhibit growth of MDA-MB-231 cells via PPARy activation and a high concentration of rosiglitazone can also induce MDA-MB-231 cell apoptosis. These results suggest that PPARy represents a putative molecular target for chemopreventive therapy and rosiglitazone may be effective in the treatment of breast cancer.
文摘目的探究视黄酸相关孤儿受体(RORγt)白细胞介素23(IL-23)通路调节辅助性T细胞17(Th17)在老年盐敏感性高血压发病中的作用。方法对内蒙古自治区的村民进行调查,2021年1月至2022年1月选取289例老年高血压患者作为研究对象,采用Sullivan盐负荷试验将患者进行分组,盐敏感高血压患者103例作为研究组,非盐敏感高血压患者186例作为对照组,给予慢性盐负荷试验。结果研究组收缩压、舒张压、MAP、心率在D10、D17均显著高于对照组(P<0.01)。2组尿量、尿钠、尿钾、尿肌酐水平在基线D3比较无显著差异(P>0.05),D10与对照组比较,研究组尿钠[(315.32±57.21)mmol/24 h vs(226.64±58.53)mmol/24 h,P=0.000]、尿肌酐[(12.46±1.64)mmol/24 h vs(10.12±1.17)mmol/24 h,P=0.000]显著增高。2组Th17比例、IL-17A水平在D4、D5、D10逐渐上升,在D17下降,且研究组Th17比例、IL-17A水平在D4、D5、D10、D17均显著高于对照组(P<0.01)。结论Th17参与了盐敏感性高血压的发生,RORγt-IL-23受体信号通路可诱导Th17细胞分化。
基金the National Natural Science Foundation of China,No.81701881the Nanjing Medical Science and Technology Development Foundation,No.YKK15098 and No.YKK17102
文摘BACKGROUND The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory response, improve immune dysfunction, and prevent enterogenic infection in critically ill patients;however, the precise mechanisms remain unclear. Considering the important roles of Th17 and Treg lymphocytes in the development of inflammatory and infectious diseases, we hypothesized that EEN could improve the immune dysfunction in sepsis by maintaining a balanced Th17/Treg cell ratio and by regulating the IL- 23/IL-17 axis. AIM To investigate the effects of EEN on the Th17/Treg cell ratios and the IL-23/IL-17 axis in septic patients. METHODS In this prospective clinical trial, patients were randomly divided into an EEN or delayed enteral nutrition (DEN) group. Enteral feeding was started within 48 h in the EEN group, whereas enteral feeding was started on the 4th day in the DEN group. The Th17 and Treg cell percentages and the interleukin levels were tested on days 1, 3, and 7 after admission. The clinical severity and outcome variables were also recorded. RESULTS Fifty-three patients were enrolled in this trial from October 2017 to June 2018. The Th17 cell percentages, Th17/Treg cell ratios, IL-17, IL-23, and IL-6 levels of the EEN group were lower than those of the DEN group on the 7th day after admission (P < 0.05). The duration of mechanical ventilation and of the intensive care unit stay of the EEN group were shorter than those of the DEN group (P <0.05). However, no difference in the 28-d mortality was found between the two groups (P = 0.728). CONCLUSION EEN could regulate the imbalance of Th17/Treg cell ratios and suppress the IL- 23/IL-17 axis during sepsis. Moreover, EEN could reduce the clinical severity of sepsis but did not reduce the 28-d mortality of septic patients.
基金supported by the National Natural Science Foundation of China (No. NSFC-81502406, 81673320)Education Scientific Research Project for young teachers, 2018 (No. JT180013)
文摘Objective: The present study aimed to investigate the molecular events in alisol B 23-acetate(ABA) cytotoxic activity against a liver cancer cell line.Methods: First, we employed a quantitative proteomics approach based on stable isotope labeling by amino acids in cell culture(SILAC) to identify the different proteins expressed in HepG2 liver cancer cells upon exposure to ABA. Next, bioinformatics analyses through DAVID and STRING on-line tools were used to predict the pathways involved. Finally, we applied functional validation including cell cycle analysis and Western blotting for apoptosis and mTOR pathway-related proteins to confirm the bioinformatics predictions.Results: We identified 330 different proteins with the SILAC-based quantitative proteomics approach. The bioinformatics analysis and the functional validation revealed that the mTOR pathway, ribosome biogenesis, cell cycle, and apoptosis pathways were differentially regulated by ABA. G1 cell cycle arrest, apoptosis and mTOR inhibition were confirmed.Conclusions: ABA, a potential mTOR inhibitor, induces the disruption of ribosomal biogenesis. It also affects the mTOR-MRP axis to cause G1 cell cycle arrest and finally leads to cancer cell apoptosis.
基金The authors thank Xin-Quan Shi, De-Yu Liu, Da-Guang Sun, Hong-Fei Xia, Qian-Xin Wang, Chong Wang, Dan Li, Xiang-Bo Xu, Yong-Jie Chang and Nan Yao for technical assistance. This work was supported by the National Natural Science Foundation of China （No. 30670784）.
文摘LM23 is a gene specifically expressed in the testis of Rattus norvegicus, as previously reported by our laboratory. The aim of the study is to further investigate the biological function of LM23. Several bioinformatic tools were utilized, including PROSITE and BLAST. To determine the subcellullar localization of LM23, a polyclonal antibody specific for LM23 was generated via the immunization of rabbits. The LM23gene was cloned from rat testis tissue, and LM23 protein was expressed in Escherichia co/i. The biological function of LM23 was analyzed with microarray analysis and immunohistochemistry, using a rat model of LM23 gene knockdown. The results suggested that LM23 belongs to the Speedy/Ringo family. LM23 regulated the GI/S and G2/M transitions of the cell cycle during spermatogenesis. Downregulation of the LM23gene during spermatogenesis could lead to the activation of both the Fas-FasL pathway and the mitochondrial pathway. These novel findings indicate that LM23 has a diverse array of functions that are important in both the life and death of the spermatogenic cell.
文摘Age-related osteoporosis is associated with the reduced capacity of bone marrow mesenchymal stem cells （BMSCs） to differentiate into osteoblasts instead of adipocytes. However, the molecular mechanisms that decide the fate of BMSCs remain unclear. In our study, microRNA-23a, and microRNA-23b （miR-23a/b） were found to be markedly downregulated in BMSCs of aged mice and humans. The overexpression of miR-23a/b in BMSCs promoted osteogenic differentiation, whereas the inhibition of miR-23a/b increased adipogenic differentiation. Transmembrane protein 64 （Tmem64）, which has expression levels inversely related to those of miR-23a/b in aged and young mice, was identified as a major target of miR-23a/b during BMSC differentiation. In conclusion, our study suggests that miR-23a/b has a critical role in the regulation of mesenchymal lineage differentiation through the suppression of Tmem64.
基金Project(31171176)supported by the National Natural Science Foundation of China
文摘Protein Rad23, a nucleotide excision repair factor, mainly involves in repairing the DNA damage from environment, such as UV light. The function of Rad23 protein involved in DNA damage repair from many environmental factors has been studied extensively, but it is not clear from ultraviolet irradiation. To further investigate the photo-protective function of Rad23 protein on HeLa cells damaged from UV light irradiation, firstly, HeLa cells were irradiated by UV light and incubated with the fusion protein of pCold-Rad23, then the cell viability and apoptosis rate were detected by MTT and Hoechst33342/Pl fluorescent staining, respectively. The results show that the recombinant Rad23 protein can protect the HeLa cells from UV irradiation, and inhibit the apoptosis of HeLa cell by UV irradiation.
基金Chengde Medical University Natural Science Foundation Projects"The Mechanism of miR-23a in the Development of Tongue Squamous Cell Carcinoma"(201722)Natural Science Foundation of Hebei Provincial Department of Education-Youth Foundatijon"The Mechanism of has-circ-0001862-miR-23a Axis in the Development of Tongue Squamous Cell Carcinoma"(QN2019079).
文摘[Objectives]To investigate the mechanism of miR-23a in the proliferation of human tongue squamous cell carcinoma cells.[Methods]Clinical tissue samples of tongue squamous cell carcinoma were collected and Tca8113 and CAL27 were cultured.Real-time quantitative PCR was performed to detect the expressions of miR-23a and PPP2R5E in clinical tissue samples of tongue squamous cell carcinoma.MTT assay,colony formation assay and growth curve assay were used to detect the effect of miR-23a and PPP2R5E on the proliferation of human tongue squamous carcinoma cell.Luciferase reporter assay verified the regulatory relationship between miR-23a and PPP2R5E.[Results]The expression of miR-23a in tongue squamous cell carcinoma was significantly up-regulated(P<0.01).miR-23a promoted the proliferation of tongue squamous cell carcinoma cells.Bioinformatics prediction and luciferin reporting experiments showed that PPP2R5E was a direct target gene of miR-23a.The expression of PPP2R5E was decreased in tongue squamous cell carcinoma.PPP2R5E inhibited the proliferation of tongue squamous cell carcinoma cells.Overexpression of PPP2R5E can reverse the proliferation promoting effect of miR-23a on tongue squamous cell carcinoma cells.[Conclusions]miR-23a can promote the proliferation of tongue squamous cell carcinoma cells through PPP2R5E and miR-23a plays an oncogene role in the occurrence and development of tongue squamous cell carcinoma.
