Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be f...Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis.To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments.We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages(BMMs)at various concentrations.TRAc P experiments were conducted to examine BQTL's impact on osteoclast differentiation.RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation.Finally,in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings.This study revealed that BQTL suppressed receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity.The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity,primarily through attenuation of the MAPK,NF-κB,and Calcineurin signaling pathways.BQTL's inhibitory capacity was further examined in vivo using an ovariectomized(OVX)rat model,demonstrating a strong protective effect against bone loss.BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.展开更多
BACKGROUND We present a case of an EWSR1/FUS::NFATC2 rearranged sarcoma in the left forearm and analyze its clinicopathological and molecular features.CASE SUMMARY The patient is a 23-year-old woman.Microscopically,th...BACKGROUND We present a case of an EWSR1/FUS::NFATC2 rearranged sarcoma in the left forearm and analyze its clinicopathological and molecular features.CASE SUMMARY The patient is a 23-year-old woman.Microscopically,the tumor cells were medium-sized round cells arranged in small nests.The cytoplasm was clear,nuclei were relatively uniform,chromatin was dense,nucleoli were visible,and mitotic figures were rare.Immunohistochemically,the tumor cells were positive for Vimentin,INI-1,CD99,NKX2.2,CyclinD1,friend leukaemia virus integration 1,and NKX3.1.Next-generation sequencing revealed the presence of the EWSR1-NFATC2 fusion gene.EWSR1/FUS::NFATC2 rearranged sarcomas are rare and can easily be misdiagnosed.CONCLUSION Clinical imaging,immunohistochemistry,and molecular pathology should be considered to confirm the diagnosis.展开更多
Objective:To investigate whether cardiac mast cells(MCs)participate in pressure overload-induced myocardial hypertrophy through the regulation of transient receptor potential vanilloid 4(TRPV4).Methods:Pressure overlo...Objective:To investigate whether cardiac mast cells(MCs)participate in pressure overload-induced myocardial hypertrophy through the regulation of transient receptor potential vanilloid 4(TRPV4).Methods:Pressure overload-induced myocardial hypertrophy was induced via abdominal aortic constriction(AAC).Myocardial hypertrophy was evaluated by measuring the heart weight index(HW/BW),lung weight index(LW/BW),ratio of heart weight to tibia length(HW/TL),ratio of lung weight to tibia length(LW/TL),and cross-sectional area of myocardial cells.qRT-PCR was used to detect the mRNA expression of TRPV4.Western blotting was used to detect the protein expression of TRPV4,mast cell tryptase,myosin heavy chain beta(β-MHC),calcineurin A(CnA),and nuclear factor of activated T-cell c3(NFATc3).ELISA was used to measure the levels of brain natriuretic peptide(BNP)and histamine.Fluo4 AM was used to detect the calcium signal in H9c2 myocardial cells.Results:Compared with those of the sham rats,the myocardial mast cells,tryptase,HW/BW,LW/BW,HW/TL,and LW/TL,the cross-sectional area of the myocardial cells,and the expression ofβ-MHC,TRPV4,CnA,and NFATc3 in the myocardial tissue and the serum BNP of the AAC-treated rats increased significantly,whereas the MC stabilizer cromolyn sodium(CS)reversed these indicators.In H9c2 cardiomyocytes,treatment with histamine and the TRPV4 agonist GSK1016790A upregulated the expression of TRPV4,β-MHC,BNP,CnA and NFATc3 and increased calcium ion influx,whereas these effects were inhibited by the H2 receptor inhibitor famotidine and the TRPV4 inhibitor HC067047.Conclusion:Cardiac MCs participate in pressure overload-induced myocardial hypertrophy through the upregulation of TRPV4 via its mediator histamine,and the Ca^(2+)/CnA/NFATc3 signaling pathway is involved in this process.展开更多
活化T细胞核因子(nuclear factor-activated T cell 1,NFATc1)是一种重要的转录因子。在破骨细胞中,它由上游RANKL信号通路的诱导、Ca^(2+)相关协同刺激信号通路与Ca^(2+)非依赖信号通路的扩增,Lhx2、IRF8、Mafb及Bcl6等细胞因子负反馈...活化T细胞核因子(nuclear factor-activated T cell 1,NFATc1)是一种重要的转录因子。在破骨细胞中,它由上游RANKL信号通路的诱导、Ca^(2+)相关协同刺激信号通路与Ca^(2+)非依赖信号通路的扩增,Lhx2、IRF8、Mafb及Bcl6等细胞因子负反馈诱导,在NFATc1转录过程中的启动、扩增及靶向作用三个阶段通过复杂交互的调节影响其下游各种靶基因及蛋白,最终介导破骨细胞的分化、融合及对无机和有机骨基质的降解作用。宏观上,NFATc1还受到外界机械应力的影响从而在破骨细胞生长过程中发挥作用;并且NFATc1的调节过程受其自身节律的影响。本文就NFATc1的结构、相关调节机制和对破骨细胞的作用研究进展进行综述。展开更多
基金supported by the Natural Science Foundation of Guangdong Province,China(No.2021A1515012168)the Administration of Traditional Chinese Medicine of Guangdong Province,China(Nos.20221146 and 20241091)+5 种基金the Basic and Applied Basic Research Fund Project in Guangdong Province,China(No.2020A1515110948)the Basic and Applied Basic Research in Jointly Funded Projects of City Schools(Institutes)Projects,China(Nos.202201020500 and 202201020295)the Project of Guangzhou Science and Technology Department,China(No.202102021040)the Guangzhou Science and Technology Plan Project,China(No.2023B03J0379)the Chinese Society of Traditional Chinese Medicine Youth Talent Lifting Project(No.2022-QNRC2-B11)the Hospital Young and Middle-aged Key Talent Cultivation Project of The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine(2023-10)。
文摘Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis.To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments.We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages(BMMs)at various concentrations.TRAc P experiments were conducted to examine BQTL's impact on osteoclast differentiation.RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation.Finally,in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings.This study revealed that BQTL suppressed receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity.The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity,primarily through attenuation of the MAPK,NF-κB,and Calcineurin signaling pathways.BQTL's inhibitory capacity was further examined in vivo using an ovariectomized(OVX)rat model,demonstrating a strong protective effect against bone loss.BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
基金Supported by The Shenzhen Science and Technology Program,No.JCYJ20220530144407017.
文摘BACKGROUND We present a case of an EWSR1/FUS::NFATC2 rearranged sarcoma in the left forearm and analyze its clinicopathological and molecular features.CASE SUMMARY The patient is a 23-year-old woman.Microscopically,the tumor cells were medium-sized round cells arranged in small nests.The cytoplasm was clear,nuclei were relatively uniform,chromatin was dense,nucleoli were visible,and mitotic figures were rare.Immunohistochemically,the tumor cells were positive for Vimentin,INI-1,CD99,NKX2.2,CyclinD1,friend leukaemia virus integration 1,and NKX3.1.Next-generation sequencing revealed the presence of the EWSR1-NFATC2 fusion gene.EWSR1/FUS::NFATC2 rearranged sarcomas are rare and can easily be misdiagnosed.CONCLUSION Clinical imaging,immunohistochemistry,and molecular pathology should be considered to confirm the diagnosis.
基金supported by grants from the National Natural Science Foundation of China(No.30872716)the Natural Science Foundation of Hubei Province(No.2015CFB288).
文摘Objective:To investigate whether cardiac mast cells(MCs)participate in pressure overload-induced myocardial hypertrophy through the regulation of transient receptor potential vanilloid 4(TRPV4).Methods:Pressure overload-induced myocardial hypertrophy was induced via abdominal aortic constriction(AAC).Myocardial hypertrophy was evaluated by measuring the heart weight index(HW/BW),lung weight index(LW/BW),ratio of heart weight to tibia length(HW/TL),ratio of lung weight to tibia length(LW/TL),and cross-sectional area of myocardial cells.qRT-PCR was used to detect the mRNA expression of TRPV4.Western blotting was used to detect the protein expression of TRPV4,mast cell tryptase,myosin heavy chain beta(β-MHC),calcineurin A(CnA),and nuclear factor of activated T-cell c3(NFATc3).ELISA was used to measure the levels of brain natriuretic peptide(BNP)and histamine.Fluo4 AM was used to detect the calcium signal in H9c2 myocardial cells.Results:Compared with those of the sham rats,the myocardial mast cells,tryptase,HW/BW,LW/BW,HW/TL,and LW/TL,the cross-sectional area of the myocardial cells,and the expression ofβ-MHC,TRPV4,CnA,and NFATc3 in the myocardial tissue and the serum BNP of the AAC-treated rats increased significantly,whereas the MC stabilizer cromolyn sodium(CS)reversed these indicators.In H9c2 cardiomyocytes,treatment with histamine and the TRPV4 agonist GSK1016790A upregulated the expression of TRPV4,β-MHC,BNP,CnA and NFATc3 and increased calcium ion influx,whereas these effects were inhibited by the H2 receptor inhibitor famotidine and the TRPV4 inhibitor HC067047.Conclusion:Cardiac MCs participate in pressure overload-induced myocardial hypertrophy through the upregulation of TRPV4 via its mediator histamine,and the Ca^(2+)/CnA/NFATc3 signaling pathway is involved in this process.
文摘活化T细胞核因子(nuclear factor-activated T cell 1,NFATc1)是一种重要的转录因子。在破骨细胞中,它由上游RANKL信号通路的诱导、Ca^(2+)相关协同刺激信号通路与Ca^(2+)非依赖信号通路的扩增,Lhx2、IRF8、Mafb及Bcl6等细胞因子负反馈诱导,在NFATc1转录过程中的启动、扩增及靶向作用三个阶段通过复杂交互的调节影响其下游各种靶基因及蛋白,最终介导破骨细胞的分化、融合及对无机和有机骨基质的降解作用。宏观上,NFATc1还受到外界机械应力的影响从而在破骨细胞生长过程中发挥作用;并且NFATc1的调节过程受其自身节律的影响。本文就NFATc1的结构、相关调节机制和对破骨细胞的作用研究进展进行综述。
