Objective This study aimed to investigate the effects of caprylic acid(C8:0)on lipid metabolism and inflammation,and examine the mechanisms underlying these effects in mice and cells.Methods Fifty-six 6-week-old male ...Objective This study aimed to investigate the effects of caprylic acid(C8:0)on lipid metabolism and inflammation,and examine the mechanisms underlying these effects in mice and cells.Methods Fifty-six 6-week-old male C57BL/6J mice were randomly allocated to four groups fed a highfat diet(HFD)without or with 2%C8:0,palmitic acid(C16:0)or eicosapentaenoic acid(EPA).RAW246.7 cells were randomly divided into five groups:normal,lipopolysaccharide(LPS),LPS+C8:0,LPS+EPA and LPS+cAMP.The serum lipid profiles,inflammatory biomolecules,and ABCA1 and JAK2/STAT3 mRNA and protein expression were measured.Results C8:0 decreased TC and LDL-C,and increased the HDL-C/LDL-C ratio after injection of LPS.Without LPS,it decreased TC in mice(P<0.05).Moreover,C8:0 decreased the inflammatory response after LPS treatment in both mice and cells(P<0.05).Mechanistic investigations in C57BL/6J mouse aortas after injection of LPS indicated that C8:0 resulted in higher ABCA1 and JAK2/STAT3 expression than that with HFD,C16:0 and EPA,and resulted in lower TNF-α,NF-κB mRNA expression than that with HFD(P<0.05).In RAW 264.7 cells,C8:0 resulted in lower expression of pNF-κBP65 than that in the LPS group,and higher protein expression of ABCA1,p-JAK2 and p-STAT3 than that in the LPS and LPS+cAMP groups(P<0.05).Conclusion Our studies demonstrated that C8:0 may play an important role in lipid metabolism and the inflammatory response,and the mechanism may be associated with ABCA1 and the p-JAK2/p-STAT3 signaling pathway.展开更多
Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanism...Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanisms.This study was carried out to ascertain the functions of cytokine receptor-like factor 1(CRLF1)in cardiac fibrosis and clarify its regulatory mechanisms.We found that CRLF1 was expressed predominantly in cardiac fibroblasts.Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction,but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-β1(TGF-β1).Gain-and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts(NMCFs)with or without TGF-β1 stimulation.CRLF1 overexpression increased cell viability,collagen production,cell proliferation capacity,and myofibroblast transformation of NMCFs with or without TGF-β1 stimulation,while silencing of CRLF1 had the opposite effects.An inhibitor of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway and different inhibitors of TGF-β1 signaling cascades,comprising mothers against decapentaplegic homolog(SMAD)-dependent and SMAD-independent pathways,were applied to investigate the mechanisms involved.CRLF1 exerted its functions by activating the ERK1/2 signaling pathway.Furthermore,the SMAD-dependent pathway,not the SMAD-independent pathway,was responsible for CRLF1 up-regulation in NMCFs treated with TGF-β1.In summary,activation of the TGF-β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression.CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway.CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.展开更多
目的探讨染色体区域稳定蛋白1(chromosomal region maintenance 1,CRM1)与细胞因子信号传导抑制因子1(suppressor of cytokine signaling 1,SOCS1)表达与胃癌演进、临床病理特征及预后的关系。方法采用免疫组化检测低级别上皮内瘤变胃组...目的探讨染色体区域稳定蛋白1(chromosomal region maintenance 1,CRM1)与细胞因子信号传导抑制因子1(suppressor of cytokine signaling 1,SOCS1)表达与胃癌演进、临床病理特征及预后的关系。方法采用免疫组化检测低级别上皮内瘤变胃组织27例、高级别上皮内瘤变胃组织26例,以及进展期胃癌组织67例及对应癌旁组织67例中CRM1及SOCS1蛋白表达水平,分析两者在不同病变胃黏膜中的变化以及与胃癌临床病理特征的关系,通过在线分析工具Kaplan-Meier Plotter、单因素及多因素Cox分析影响胃癌患者预后的相关因素。结果胃癌组织中CRM1表达高于癌旁组织,SOCS1表达低于癌旁组织及瘤变组织(P<0.05);CRM1在胃癌组织高表达与浸润深度及淋巴结转移有关(P<0.05);生存分析显示高表达CRM1提示预后不良(P<0.05),SOCS1表达水平与预后无关(P>0.05);在胃癌组织中,CRM1与SOCS1表达无显著相关性(R=-0.025,P=0.842)。结论CRM1和SOCS1参与胃癌发生,CRM1高表达可能参与胃癌侵袭及转移等恶性进展。展开更多
基金supported by the National Natural Science Fund of China[no.81703204].
文摘Objective This study aimed to investigate the effects of caprylic acid(C8:0)on lipid metabolism and inflammation,and examine the mechanisms underlying these effects in mice and cells.Methods Fifty-six 6-week-old male C57BL/6J mice were randomly allocated to four groups fed a highfat diet(HFD)without or with 2%C8:0,palmitic acid(C16:0)or eicosapentaenoic acid(EPA).RAW246.7 cells were randomly divided into five groups:normal,lipopolysaccharide(LPS),LPS+C8:0,LPS+EPA and LPS+cAMP.The serum lipid profiles,inflammatory biomolecules,and ABCA1 and JAK2/STAT3 mRNA and protein expression were measured.Results C8:0 decreased TC and LDL-C,and increased the HDL-C/LDL-C ratio after injection of LPS.Without LPS,it decreased TC in mice(P<0.05).Moreover,C8:0 decreased the inflammatory response after LPS treatment in both mice and cells(P<0.05).Mechanistic investigations in C57BL/6J mouse aortas after injection of LPS indicated that C8:0 resulted in higher ABCA1 and JAK2/STAT3 expression than that with HFD,C16:0 and EPA,and resulted in lower TNF-α,NF-κB mRNA expression than that with HFD(P<0.05).In RAW 264.7 cells,C8:0 resulted in lower expression of pNF-κBP65 than that in the LPS group,and higher protein expression of ABCA1,p-JAK2 and p-STAT3 than that in the LPS and LPS+cAMP groups(P<0.05).Conclusion Our studies demonstrated that C8:0 may play an important role in lipid metabolism and the inflammatory response,and the mechanism may be associated with ABCA1 and the p-JAK2/p-STAT3 signaling pathway.
基金supported by the National Key Research and Development Project of China(No.2018YFA0800404)the National Natural Science Foundation of China(Nos.82100255 and 81970736)the China Postdoctoral Science Foundation(Nos.2021M691459 and 2022T150299).
文摘Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanisms.This study was carried out to ascertain the functions of cytokine receptor-like factor 1(CRLF1)in cardiac fibrosis and clarify its regulatory mechanisms.We found that CRLF1 was expressed predominantly in cardiac fibroblasts.Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction,but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-β1(TGF-β1).Gain-and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts(NMCFs)with or without TGF-β1 stimulation.CRLF1 overexpression increased cell viability,collagen production,cell proliferation capacity,and myofibroblast transformation of NMCFs with or without TGF-β1 stimulation,while silencing of CRLF1 had the opposite effects.An inhibitor of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway and different inhibitors of TGF-β1 signaling cascades,comprising mothers against decapentaplegic homolog(SMAD)-dependent and SMAD-independent pathways,were applied to investigate the mechanisms involved.CRLF1 exerted its functions by activating the ERK1/2 signaling pathway.Furthermore,the SMAD-dependent pathway,not the SMAD-independent pathway,was responsible for CRLF1 up-regulation in NMCFs treated with TGF-β1.In summary,activation of the TGF-β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression.CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway.CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.
文摘目的探讨染色体区域稳定蛋白1(chromosomal region maintenance 1,CRM1)与细胞因子信号传导抑制因子1(suppressor of cytokine signaling 1,SOCS1)表达与胃癌演进、临床病理特征及预后的关系。方法采用免疫组化检测低级别上皮内瘤变胃组织27例、高级别上皮内瘤变胃组织26例,以及进展期胃癌组织67例及对应癌旁组织67例中CRM1及SOCS1蛋白表达水平,分析两者在不同病变胃黏膜中的变化以及与胃癌临床病理特征的关系,通过在线分析工具Kaplan-Meier Plotter、单因素及多因素Cox分析影响胃癌患者预后的相关因素。结果胃癌组织中CRM1表达高于癌旁组织,SOCS1表达低于癌旁组织及瘤变组织(P<0.05);CRM1在胃癌组织高表达与浸润深度及淋巴结转移有关(P<0.05);生存分析显示高表达CRM1提示预后不良(P<0.05),SOCS1表达水平与预后无关(P>0.05);在胃癌组织中,CRM1与SOCS1表达无显著相关性(R=-0.025,P=0.842)。结论CRM1和SOCS1参与胃癌发生,CRM1高表达可能参与胃癌侵袭及转移等恶性进展。
