Objective:Diagnosis of immunoglobulin A nephropathy(IgAN)requires the evaluation of renal biopsy specimens.However,renal biopsy is an invasive procedure and is not frequently performed for various reasons.Thus,recogni...Objective:Diagnosis of immunoglobulin A nephropathy(IgAN)requires the evaluation of renal biopsy specimens.However,renal biopsy is an invasive procedure and is not frequently performed for various reasons.Thus,recognized noninvasive biomarkers for predicting IgAN progression are urgently needed.Methods:In the present study,we included 86 IgAN patients with renal biopsy from June 2015 to May 2016 and had their plasma interleukin-7(IL-7)level measured with ELISA.The association between the plasma IL-7 level and clinico-pathological characteristics was analyzed.Immunohistochemical staining was used to assay the in situ expression of IL-7 in vivo.Western blotting was perfonned to examine the production of extracellular matrix,p-mTOR and the markers of autophagy under the treatment of IL-7 after TGF-β1 stimulation in renal tubular epithelial cells.Results:IL-7 was significantly decreased in patients with IgAN compared to healthy subjects(2.3077 vs.8.6294 pg/mL,P<0.0001).There was a significant difference in the plasma IL-7 level between tubular atrophy/interstitial fibrosis TO and T2 classes(P=0.0064).A lower plasma IL-7 value in patients at the time of biopsy indicated a poor renal outcome.In addition,IL-7 was over-expressed in renal tubular epithelial cells and significantly attenuated transforming growth factor β1-induced extracellular matrix production by suppression of cellular autophagy via activation of mTOR1 signaling.Conclusion:These results suggested that IL-7 might be a noninvasive biomarker for predicating IgAN.It protected renal proximal tubular epithelial cells from cellular fibrosis by inhibiting autophagy via mTORl signaling.展开更多
The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
针对触摸屏监控系统不能满足大中型立体仓库对数据进行存储和处理的功能需求,在Visual Studio 2019集成开发环境中,采用C#语言开发一套立体仓库上位机控制系统。以多线程的方式实时读取库位信息;以S7-1200 PLC作为主控制器,设计产品的...针对触摸屏监控系统不能满足大中型立体仓库对数据进行存储和处理的功能需求,在Visual Studio 2019集成开发环境中,采用C#语言开发一套立体仓库上位机控制系统。以多线程的方式实时读取库位信息;以S7-1200 PLC作为主控制器,设计产品的自动入库和自动出库程序流程,采用SCL语言设计了库位先进先出的控制程序。C#和S7-1200 PLC之间采用S7通信的方式控制立体仓库的出入库操作和库位信息采集,3年的现场运行情况表明,整个系统能在上位机上对立体仓库进行手动控制和自动控制,能精确快速地进行入库出库操作,运行平稳,上位机上能正确实时显示库位信息,达到了预期的结果。展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th...BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.展开更多
基金supported by grants from Huazhong University of Science and Technology Research Funds for Self-dependent Innovation(No.2017KFYXJJ101)the National Natural Science Foundation of China(No.81703058,No.81970591,and No.82000656).
文摘Objective:Diagnosis of immunoglobulin A nephropathy(IgAN)requires the evaluation of renal biopsy specimens.However,renal biopsy is an invasive procedure and is not frequently performed for various reasons.Thus,recognized noninvasive biomarkers for predicting IgAN progression are urgently needed.Methods:In the present study,we included 86 IgAN patients with renal biopsy from June 2015 to May 2016 and had their plasma interleukin-7(IL-7)level measured with ELISA.The association between the plasma IL-7 level and clinico-pathological characteristics was analyzed.Immunohistochemical staining was used to assay the in situ expression of IL-7 in vivo.Western blotting was perfonned to examine the production of extracellular matrix,p-mTOR and the markers of autophagy under the treatment of IL-7 after TGF-β1 stimulation in renal tubular epithelial cells.Results:IL-7 was significantly decreased in patients with IgAN compared to healthy subjects(2.3077 vs.8.6294 pg/mL,P<0.0001).There was a significant difference in the plasma IL-7 level between tubular atrophy/interstitial fibrosis TO and T2 classes(P=0.0064).A lower plasma IL-7 value in patients at the time of biopsy indicated a poor renal outcome.In addition,IL-7 was over-expressed in renal tubular epithelial cells and significantly attenuated transforming growth factor β1-induced extracellular matrix production by suppression of cellular autophagy via activation of mTOR1 signaling.Conclusion:These results suggested that IL-7 might be a noninvasive biomarker for predicating IgAN.It protected renal proximal tubular epithelial cells from cellular fibrosis by inhibiting autophagy via mTORl signaling.
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
文摘针对触摸屏监控系统不能满足大中型立体仓库对数据进行存储和处理的功能需求,在Visual Studio 2019集成开发环境中,采用C#语言开发一套立体仓库上位机控制系统。以多线程的方式实时读取库位信息;以S7-1200 PLC作为主控制器,设计产品的自动入库和自动出库程序流程,采用SCL语言设计了库位先进先出的控制程序。C#和S7-1200 PLC之间采用S7通信的方式控制立体仓库的出入库操作和库位信息采集,3年的现场运行情况表明,整个系统能在上位机上对立体仓库进行手动控制和自动控制,能精确快速地进行入库出库操作,运行平稳,上位机上能正确实时显示库位信息,达到了预期的结果。
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.
