Traumatic brain injury （TBI） results in a range of neuroinflam- matory events that vary depending on the type and extent of in- jury. Central to this is the activation of tissue resident microglia and infiltration o...Traumatic brain injury （TBI） results in a range of neuroinflam- matory events that vary depending on the type and extent of in- jury. Central to this is the activation of tissue resident microglia and infiltration of peripheral macrophages, which phagocytose debris and/or secrete a range of cytokines, chemokines and oth- er factors which modify the injured environment to promote or inhibit repair （Schwartz et al., 2013）. The reactive macro- phages/microglia are broadly divided into two categories.展开更多
目的探讨细胞因子信号传导抑制蛋白2(SOCS2)和SOCS5在儿童过敏性紫癜(HSP)中的表达及其意义。方法应用逆转录聚合酶链反应检测HSP患儿(36例)和正常健康对照儿童(17例)外周血单个核细胞中SOCS2和SOCS5 m RNA表达水平。结果 HSP患儿SOCS2...目的探讨细胞因子信号传导抑制蛋白2(SOCS2)和SOCS5在儿童过敏性紫癜(HSP)中的表达及其意义。方法应用逆转录聚合酶链反应检测HSP患儿(36例)和正常健康对照儿童(17例)外周血单个核细胞中SOCS2和SOCS5 m RNA表达水平。结果 HSP患儿SOCS2和SOCS5 m RNA表达水平高于对照儿童(P<0.05)。混合型HSP患儿SOCS2和SOCS5 m RNA表达水平较单纯型患儿升高(P<0.05)。HSP患儿SOCS2和SOCS5 m RNA表达水平无性别差异(P>0.05)。结论 SOCS2、SOCS5可能参与儿童HSP的发病。展开更多
目的:研究肥胖小鼠及正常小鼠不同周龄下丘脑组织SH2B1(adapter protein with a Src-homology 2 domain),细胞因子信号转导抑制蛋白3(the suppressor of cytokine signaling-3,SOCS3),蛋白质酪氨酸磷酸酶1B(proteintyrosine phosphatase...目的:研究肥胖小鼠及正常小鼠不同周龄下丘脑组织SH2B1(adapter protein with a Src-homology 2 domain),细胞因子信号转导抑制蛋白3(the suppressor of cytokine signaling-3,SOCS3),蛋白质酪氨酸磷酸酶1B(proteintyrosine phosphatase 1B,PTP1B)和神经肽Y(neturopetide Y,NPY)表达的变化规律及其与血清瘦素及胰岛素水平的关系。方法:选用健康C57BL/6乳鼠制作肥胖动物模型,计算Lee’s指数及稳态模型胰岛素抵抗指数。荧光定量RT-PCR法检测下丘脑SH2B1,SOCS3及PTP1B mRNA表达量,Western印迹检测下丘脑SH2B1和NPY蛋白表达量。结果:与同周龄对照组小鼠相比,肥胖组小鼠下丘脑组织SH2B1 mRNA表达减少,SOCS3及PTP1B mRNA表达增加;Western印迹结果显示:肥胖组小鼠SH2B1蛋白表达水平较对照组下降,NPY表达升高。直线相关分析显示:血清瘦素和血清空腹胰岛素水平与SH2B1 mRNA表达呈负相关,与SOCS3及PTP1B mRNA表达正相关。结论:SH2B1,SOCS3,PTP1B及NPY是肥胖发生、发展过程中的关键因子。展开更多
AIM： To investigate if an immune imbalance may account for the development and progression of chronic radiation enteritis. We analyzed the Th1/Th2 immune response profile early and 6 mo after fractionated colorectal ...AIM： To investigate if an immune imbalance may account for the development and progression of chronic radiation enteritis. We analyzed the Th1/Th2 immune response profile early and 6 mo after fractionated colorectal irradiation. METHODS： A rat model of fractionated colorectal γ-irradiation （4-Gy fractions, 3 fractions per week） was designed to investigate the effects of cumulative dose on inflammatory mediators （cytokines and chemo- kines） and immune response （Th1/Th2 profile and immunosuppressive mediator IL-10） during acute （early） response and 6 mo after the end of fractionated irradiation （chronic response）. Analyses were performed 1 d after the cumulative doses of 16 Gy and 36 Gy and 1 d, 3 d, and 26 wk after the cumulative dose of 52 Gy. RESULTS： Without causing histological damage, fractionated radiation induced elevated expression of IL-1β, TNFα, MCP-1, and iNOS in distal colonic mucosa during the early post-irradiation phase. At that time, a Th2 profile was confirmed by expression of both the Th2- specific transcription factor GATA-3 and the chemokine receptor CCR4 and by suppression of the Thl cytokine IFNγ/IP-10 throughout the irradiation protocol. After 6 mo, despite the 2-fold reduction of iNOS and MCP-1 levels, the Th2 profile persisted, as shown by a 50% reduction in the expression of the Thl transcription factor T-bet, the chemokine receptor CCXCR3, and the IFNγ/ STAT1 pathway. At the same time-point, the immunosuppressive IL-10/STAT3 pathway, known to regulate the Th1/Th2 balance, was expressed, in irradiated rats, at approximately half its level as compared to controls.This suppression was associated with an overexpression of SOCS3, which inhibits the feedback of the Thl polarization and regulates IL-10 production. CONCLUSION： Colorectal irradiation induces Th2 polarization, defective IL-10/STAT3 pathway activation and SOCS3 overexpression. These changes, in turn, maintain a immunological imbalance that persists in the long term.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the most prevalent human cancers with high mortality.Long non-coding RNA heart and neural crest derivatives expressed 2 anti-sense 1(HAND2-AS1)is down-regulated in sev...Background:Hepatocellular carcinoma(HCC)is one of the most prevalent human cancers with high mortality.Long non-coding RNA heart and neural crest derivatives expressed 2 anti-sense 1(HAND2-AS1)is down-regulated in several cancers including HCC,yet the precise mechanisms how HAND2-AS1 regulates cell survival in HCC remains poorly understood.Methods:The expression levels of HAND2-AS1 and miR-300 were measured using quantitative real-time PCR.The protein levels of suppressor of cytokine signaling 5(SOCS5),Bcl-2,Bax and cleaved caspase-3 were determined by Western blot.Cell viability and cell proliferation were assessed using cell counting kit-8 and clone formation assay,respectively.Cell apoptosis was detected using flow cytometry.The interactions between HAND2-AS1 and miR-300,miR-300 and SOCS5 were validated using luciferase reporter assay.Results:HAND2-AS1 was down-regulated in HCC tissues and cell lines,and the expression level of HAND2-AS1 was positively correlated to patient survival.HAND2-AS1 over-expression reduced viability and proliferation in HCC cells.Elevated HAND2-AS1 level induced apoptosis in HCC cells,accompanied with increased Bax and cleaved caspase-3 levels and decreased Bcl-2 level.We also validated that HAND2-AS1 acted as a sponge of miR-300,and there was a negative correlation between expression levels of HAND2-AS1 and miR-300 in HCC tissues.Furthermore,we found that SOCS5 was a downstream target of miR-300.In addition,miR-300 mimics abolished HAND2-AS1-mediated inhibition of cell viability and proliferation.miR-300 mimics also reversed the HAND2-AS1-induced apoptosis in HCC cells.Conclusion:lncRNA HAND2-AS1 inhibits proliferation in HCC through regulating miR-300/SOCS5 axis.展开更多
BACKGROUND:Exosomes and exosomal microRNAs have been implicated in tumor occurrence and metastasis.Our previous study showed that microRNA-761(miR-761)is overexpressed in hepatocellular carcinoma(HCC)tissues and that ...BACKGROUND:Exosomes and exosomal microRNAs have been implicated in tumor occurrence and metastasis.Our previous study showed that microRNA-761(miR-761)is overexpressed in hepatocellular carcinoma(HCC)tissues and that its inhibition affects mitochondrial function and inhibits HCC metastasis.The mechanism by which exosomal miR-761 modulates the tumor microenvironment has not been elucidated.METHODS:Exosomal miR-761 was detected in six cell lines.Cell counting kit-8(CCK-8)and transwell migration assays were performed to determine the function of exosomal miR-761 in HCC cells.The luciferase reporter assay was used to analyze miR-761 target genes in normal fi broblasts(NFs).The inhibitors AZD1480 and C188-9 were employed to determine the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway in the transformation of cancer-associated fi broblasts(CAFs).RESULTS:In this study,we characterized the mechanism by which miR-761 reprogrammed the tumor microenvironment.We found that HCC-derived exosomal miR-761 was taken up by NFs.Moreover,HCC exosomes aff ected the tumor microenvironment by activating NFs via suppressor of cytokine signaling 2(SOCS2)and the JAK2/STAT3 signaling pathway.CONCLUSIONS:These results demonstrated that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs.Our fi ndings may inspire new strategies for HCC prevention and therapy.展开更多
基金supported by the National Health and Medical Research Council of AustraliaProject grant 1045125 and Fellowship(to AMT)628344support from Stem Cells Australia
文摘Traumatic brain injury （TBI） results in a range of neuroinflam- matory events that vary depending on the type and extent of in- jury. Central to this is the activation of tissue resident microglia and infiltration of peripheral macrophages, which phagocytose debris and/or secrete a range of cytokines, chemokines and oth- er factors which modify the injured environment to promote or inhibit repair （Schwartz et al., 2013）. The reactive macro- phages/microglia are broadly divided into two categories.
文摘目的探讨细胞因子信号传导抑制蛋白2(SOCS2)和SOCS5在儿童过敏性紫癜(HSP)中的表达及其意义。方法应用逆转录聚合酶链反应检测HSP患儿(36例)和正常健康对照儿童(17例)外周血单个核细胞中SOCS2和SOCS5 m RNA表达水平。结果 HSP患儿SOCS2和SOCS5 m RNA表达水平高于对照儿童(P<0.05)。混合型HSP患儿SOCS2和SOCS5 m RNA表达水平较单纯型患儿升高(P<0.05)。HSP患儿SOCS2和SOCS5 m RNA表达水平无性别差异(P>0.05)。结论 SOCS2、SOCS5可能参与儿童HSP的发病。
文摘目的:研究肥胖小鼠及正常小鼠不同周龄下丘脑组织SH2B1(adapter protein with a Src-homology 2 domain),细胞因子信号转导抑制蛋白3(the suppressor of cytokine signaling-3,SOCS3),蛋白质酪氨酸磷酸酶1B(proteintyrosine phosphatase 1B,PTP1B)和神经肽Y(neturopetide Y,NPY)表达的变化规律及其与血清瘦素及胰岛素水平的关系。方法:选用健康C57BL/6乳鼠制作肥胖动物模型,计算Lee’s指数及稳态模型胰岛素抵抗指数。荧光定量RT-PCR法检测下丘脑SH2B1,SOCS3及PTP1B mRNA表达量,Western印迹检测下丘脑SH2B1和NPY蛋白表达量。结果:与同周龄对照组小鼠相比,肥胖组小鼠下丘脑组织SH2B1 mRNA表达减少,SOCS3及PTP1B mRNA表达增加;Western印迹结果显示:肥胖组小鼠SH2B1蛋白表达水平较对照组下降,NPY表达升高。直线相关分析显示:血清瘦素和血清空腹胰岛素水平与SH2B1 mRNA表达呈负相关,与SOCS3及PTP1B mRNA表达正相关。结论:SH2B1,SOCS3,PTP1B及NPY是肥胖发生、发展过程中的关键因子。
文摘AIM： To investigate if an immune imbalance may account for the development and progression of chronic radiation enteritis. We analyzed the Th1/Th2 immune response profile early and 6 mo after fractionated colorectal irradiation. METHODS： A rat model of fractionated colorectal γ-irradiation （4-Gy fractions, 3 fractions per week） was designed to investigate the effects of cumulative dose on inflammatory mediators （cytokines and chemo- kines） and immune response （Th1/Th2 profile and immunosuppressive mediator IL-10） during acute （early） response and 6 mo after the end of fractionated irradiation （chronic response）. Analyses were performed 1 d after the cumulative doses of 16 Gy and 36 Gy and 1 d, 3 d, and 26 wk after the cumulative dose of 52 Gy. RESULTS： Without causing histological damage, fractionated radiation induced elevated expression of IL-1β, TNFα, MCP-1, and iNOS in distal colonic mucosa during the early post-irradiation phase. At that time, a Th2 profile was confirmed by expression of both the Th2- specific transcription factor GATA-3 and the chemokine receptor CCR4 and by suppression of the Thl cytokine IFNγ/IP-10 throughout the irradiation protocol. After 6 mo, despite the 2-fold reduction of iNOS and MCP-1 levels, the Th2 profile persisted, as shown by a 50% reduction in the expression of the Thl transcription factor T-bet, the chemokine receptor CCXCR3, and the IFNγ/ STAT1 pathway. At the same time-point, the immunosuppressive IL-10/STAT3 pathway, known to regulate the Th1/Th2 balance, was expressed, in irradiated rats, at approximately half its level as compared to controls.This suppression was associated with an overexpression of SOCS3, which inhibits the feedback of the Thl polarization and regulates IL-10 production. CONCLUSION： Colorectal irradiation induces Th2 polarization, defective IL-10/STAT3 pathway activation and SOCS3 overexpression. These changes, in turn, maintain a immunological imbalance that persists in the long term.
文摘Background:Hepatocellular carcinoma(HCC)is one of the most prevalent human cancers with high mortality.Long non-coding RNA heart and neural crest derivatives expressed 2 anti-sense 1(HAND2-AS1)is down-regulated in several cancers including HCC,yet the precise mechanisms how HAND2-AS1 regulates cell survival in HCC remains poorly understood.Methods:The expression levels of HAND2-AS1 and miR-300 were measured using quantitative real-time PCR.The protein levels of suppressor of cytokine signaling 5(SOCS5),Bcl-2,Bax and cleaved caspase-3 were determined by Western blot.Cell viability and cell proliferation were assessed using cell counting kit-8 and clone formation assay,respectively.Cell apoptosis was detected using flow cytometry.The interactions between HAND2-AS1 and miR-300,miR-300 and SOCS5 were validated using luciferase reporter assay.Results:HAND2-AS1 was down-regulated in HCC tissues and cell lines,and the expression level of HAND2-AS1 was positively correlated to patient survival.HAND2-AS1 over-expression reduced viability and proliferation in HCC cells.Elevated HAND2-AS1 level induced apoptosis in HCC cells,accompanied with increased Bax and cleaved caspase-3 levels and decreased Bcl-2 level.We also validated that HAND2-AS1 acted as a sponge of miR-300,and there was a negative correlation between expression levels of HAND2-AS1 and miR-300 in HCC tissues.Furthermore,we found that SOCS5 was a downstream target of miR-300.In addition,miR-300 mimics abolished HAND2-AS1-mediated inhibition of cell viability and proliferation.miR-300 mimics also reversed the HAND2-AS1-induced apoptosis in HCC cells.Conclusion:lncRNA HAND2-AS1 inhibits proliferation in HCC through regulating miR-300/SOCS5 axis.
基金This work was supported by the National Natural Science Foundation of China(82072203)Natural Science Foundation of Zhejiang Province(LQ19H160025).
文摘BACKGROUND:Exosomes and exosomal microRNAs have been implicated in tumor occurrence and metastasis.Our previous study showed that microRNA-761(miR-761)is overexpressed in hepatocellular carcinoma(HCC)tissues and that its inhibition affects mitochondrial function and inhibits HCC metastasis.The mechanism by which exosomal miR-761 modulates the tumor microenvironment has not been elucidated.METHODS:Exosomal miR-761 was detected in six cell lines.Cell counting kit-8(CCK-8)and transwell migration assays were performed to determine the function of exosomal miR-761 in HCC cells.The luciferase reporter assay was used to analyze miR-761 target genes in normal fi broblasts(NFs).The inhibitors AZD1480 and C188-9 were employed to determine the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway in the transformation of cancer-associated fi broblasts(CAFs).RESULTS:In this study,we characterized the mechanism by which miR-761 reprogrammed the tumor microenvironment.We found that HCC-derived exosomal miR-761 was taken up by NFs.Moreover,HCC exosomes aff ected the tumor microenvironment by activating NFs via suppressor of cytokine signaling 2(SOCS2)and the JAK2/STAT3 signaling pathway.CONCLUSIONS:These results demonstrated that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs.Our fi ndings may inspire new strategies for HCC prevention and therapy.
