目的:探究肿瘤坏死因子配体超家族成员-15(TNFSF15)是否能够抑制小鼠脑梗死后的炎症反应、氧化应激及脑损伤。方法:基于小鼠的脑梗死模型,通过腹腔注射TNFSF15组,利用行为学测试、Nissl染色、TUNEL染色、免疫组织化学染色及RT-PCR评估...目的:探究肿瘤坏死因子配体超家族成员-15(TNFSF15)是否能够抑制小鼠脑梗死后的炎症反应、氧化应激及脑损伤。方法:基于小鼠的脑梗死模型,通过腹腔注射TNFSF15组,利用行为学测试、Nissl染色、TUNEL染色、免疫组织化学染色及RT-PCR评估梗死灶相关情况。结果:相比于生理盐水组,TNFSF15明显改善脑梗死后小鼠的行为学评分,在转角测试中,TNFSF15组小鼠向左转身的频率明显降低(62.50%VS 68.00%,P<0.05);在黏合剂去除试验中,TNFSF15组的小鼠去除右前爪上黏性胶布的时间明显减少(20.0s VS 23.2s,P<0.01);TNFSF15明显减少脑梗死体积(13.57mm^(3) VS 20.57mm^(3),P<0.01);显著抑制梗死灶周围神经元的凋亡(24.75%VS 40.38%,P=0.003);明显抑制巨噬细胞的浸润(14.4%VS 7.7%,P<0.01);RT-PCR证实,TNFSF15增加抗氧化酶基因(GPX1、SOD1)的表达,减少NADPH氧化酶基因(NOX2、p22phox)的表达。结论:TNFSF15可能是通过调节小鼠脑梗死后的氧化应激反应,改善脑梗死后小鼠的行为学评分,减少梗死灶面积和体积,抑制梗死灶周围神经元的凋亡,抑制巨噬细胞的浸润。展开更多
Objective:Immature vasculature lacking pericyte coverage substantially contributes to tumor growth,drug resistance,and cancer cell dissemination.We previously demonstrated that tumor necrosis factor superfamily 15(TNF...Objective:Immature vasculature lacking pericyte coverage substantially contributes to tumor growth,drug resistance,and cancer cell dissemination.We previously demonstrated that tumor necrosis factor superfamily 15(TNFSF15)is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis.The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b^(+) cells and further into pericytes.Methods:A model of Lewis lung cancer was established in mice with red fluorescent bone marrow.After TNFSF15 treatment,CD11b^(+) myeloid cells and vascular pericytes in the tumors,and the co-localization of pericytes and vascular endothelial cells,were assessed.Additionally,CD11b^(+) cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.Results:We observed elevated percentages of bone marrow-derived CD11b^(+)myeloid cells and vascular pericytes in TNFSF15-treated tumors,and the latter cells co-localized with vascular endothelial cells.TNFSF15 protected against CD11b^(+)cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.Conclusions:TNFSF15 facilitates the production of CD11b^(+) cells in the bone marrow and promotes the differentiation of these cells into pericytes,which may stabilize the tumor neovasculature.展开更多
目的探讨胰岛素样生长因子结合蛋白-3(IGFBP3)和肿瘤坏死因子超家族成员-15(TNFSF15)在银屑病发生发展中的作用及临床意义。方法分离扩增15例银屑病患者皮损及15例正常人皮肤的间充质干细胞,采用实时荧光定量聚合酶链反应(RT-PCR)分别检...目的探讨胰岛素样生长因子结合蛋白-3(IGFBP3)和肿瘤坏死因子超家族成员-15(TNFSF15)在银屑病发生发展中的作用及临床意义。方法分离扩增15例银屑病患者皮损及15例正常人皮肤的间充质干细胞,采用实时荧光定量聚合酶链反应(RT-PCR)分别检测IGFBP3和TNFSF15的m RNA表达水平。结果银屑病患者皮肤间充质干细胞中IGFBP3和TNFSF15 m RNA表达水平较对照组明显降低,且差异具有统计学意义(P<0.05)。结论银屑病患者皮肤间充质干细胞IGFBP3 m RNA表达降低可能与银屑病角质形成细胞增殖活性增高及皮损局部血管形成增加有关。而TNFSF15 m RNA表达降低可能与银屑病皮损处血管内皮细胞的增殖有关。展开更多
Background:The genetic variant of tumor necrosis factor superfamily member 15(TNFSF15)is associated with Crohn’s disease(CD)and the development of intestinal fibrosis and stricturing.We aimed to investigate its predi...Background:The genetic variant of tumor necrosis factor superfamily member 15(TNFSF15)is associated with Crohn’s disease(CD)and the development of intestinal fibrosis and stricturing.We aimed to investigate its predictive role in disease progression and the impact of ileal fibrosis-associated protein expression in Chinese patients with CD.Methods:We genotyped the single nucleotide polymorphism rs6478109 within the TNFSF15 gene in 428 CD patients and 450 health controls to assess its association with CD.Genotype-phenotype correlation analyses were performed.Mucosal samples from non-diseased terminal ileum were analyzed for TL1A and fibrosis-associated protein expression using western blot and immunohistochemistry.Results:The G allele frequency of rs6478109 was significantly higher among CD patients compared with health controls(63.3%vs.46.7%,P<0.001).Patients with GG genotype were more predisposed to develop the stricturing phenotype,compared with those with AA?AG genotypes with a hazard ratio of 1.426(95%confidence interval:1.029-1.977,P=0.033).This trend was similarly observed in patients utilizing biological agents,with a hazard ratio of 4.396(95%confidence interval:1.780-10.854,P=0.001).Furthermore,increased TL1A,pro-fibrotic proteins,and TGFβ1/Smad3 pathway activation were observed in non-diseased ileal mucosa of patients with GG genotype compared with those with AA genotype.Conclusions:The TNFSF15 risk genotype GG could promote the expression of pro-fibrotic proteins and may serve as a predictor for stricturing CD.展开更多
Inflammatory bowel disease is a group of diseases that includes Crohn＇s disease （CD） and ulcerative colitis. CD is characterized as a chronic inflammatory disease of the gastrointestinal tract, ranging from the mou...Inflammatory bowel disease is a group of diseases that includes Crohn＇s disease （CD） and ulcerative colitis. CD is characterized as a chronic inflammatory disease of the gastrointestinal tract, ranging from the mouth to the anus. Although there are gross pathological and histological similarities between CD and Johne＇s dis- ease of cattle, the cause of CD remains controversial. It is vital to understand fully the cause of this disease because it affects approximately 500 000 people in North America and Europe. It ranges from 27 to 48 cases per 100 000 people. There are many theories on the cause of CD ranging from possible association with environmental factors including microorganisms to imbalance in the intestinal normal flora of the pa- tients. Regardless of the environmental trigger, there is strong evidence that a genetic disposition is a major key in acquiring CD. Many studies have proven the link between mutations in the ATG16L, NOD2/CARD15, IBDS, CTLA4, TNFSF15 and IL23R genes, and CD. The purpose of this review is to examine all genetic aspects and theories of CD, including up to date multiple popu- lation studies performed worldwide.展开更多
文摘目的:探究肿瘤坏死因子配体超家族成员-15(TNFSF15)是否能够抑制小鼠脑梗死后的炎症反应、氧化应激及脑损伤。方法:基于小鼠的脑梗死模型,通过腹腔注射TNFSF15组,利用行为学测试、Nissl染色、TUNEL染色、免疫组织化学染色及RT-PCR评估梗死灶相关情况。结果:相比于生理盐水组,TNFSF15明显改善脑梗死后小鼠的行为学评分,在转角测试中,TNFSF15组小鼠向左转身的频率明显降低(62.50%VS 68.00%,P<0.05);在黏合剂去除试验中,TNFSF15组的小鼠去除右前爪上黏性胶布的时间明显减少(20.0s VS 23.2s,P<0.01);TNFSF15明显减少脑梗死体积(13.57mm^(3) VS 20.57mm^(3),P<0.01);显著抑制梗死灶周围神经元的凋亡(24.75%VS 40.38%,P=0.003);明显抑制巨噬细胞的浸润(14.4%VS 7.7%,P<0.01);RT-PCR证实,TNFSF15增加抗氧化酶基因(GPX1、SOD1)的表达,减少NADPH氧化酶基因(NOX2、p22phox)的表达。结论:TNFSF15可能是通过调节小鼠脑梗死后的氧化应激反应,改善脑梗死后小鼠的行为学评分,减少梗死灶面积和体积,抑制梗死灶周围神经元的凋亡,抑制巨噬细胞的浸润。
基金supported partly by the National Natural Science Foundation of China(Grant Nos.82073064 and 81874167 to LYL,and 82073233 to ZQZ)Haihe Laboratory of Cell Ecosystem Innovation Fund(Grant No.22HHXBSS00020 to LYL)Ministry of Education 111 Project(Grant No.B20016 to LYL)。
文摘Objective:Immature vasculature lacking pericyte coverage substantially contributes to tumor growth,drug resistance,and cancer cell dissemination.We previously demonstrated that tumor necrosis factor superfamily 15(TNFSF15)is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis.The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b^(+) cells and further into pericytes.Methods:A model of Lewis lung cancer was established in mice with red fluorescent bone marrow.After TNFSF15 treatment,CD11b^(+) myeloid cells and vascular pericytes in the tumors,and the co-localization of pericytes and vascular endothelial cells,were assessed.Additionally,CD11b^(+) cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.Results:We observed elevated percentages of bone marrow-derived CD11b^(+)myeloid cells and vascular pericytes in TNFSF15-treated tumors,and the latter cells co-localized with vascular endothelial cells.TNFSF15 protected against CD11b^(+)cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.Conclusions:TNFSF15 facilitates the production of CD11b^(+) cells in the bone marrow and promotes the differentiation of these cells into pericytes,which may stabilize the tumor neovasculature.
文摘目的探讨胰岛素样生长因子结合蛋白-3(IGFBP3)和肿瘤坏死因子超家族成员-15(TNFSF15)在银屑病发生发展中的作用及临床意义。方法分离扩增15例银屑病患者皮损及15例正常人皮肤的间充质干细胞,采用实时荧光定量聚合酶链反应(RT-PCR)分别检测IGFBP3和TNFSF15的m RNA表达水平。结果银屑病患者皮肤间充质干细胞中IGFBP3和TNFSF15 m RNA表达水平较对照组明显降低,且差异具有统计学意义(P<0.05)。结论银屑病患者皮肤间充质干细胞IGFBP3 m RNA表达降低可能与银屑病角质形成细胞增殖活性增高及皮损局部血管形成增加有关。而TNFSF15 m RNA表达降低可能与银屑病皮损处血管内皮细胞的增殖有关。
基金supported by the Sun Yat-sen University Clinical Research 5010 Program[grant number 2014008]the National Natural Science Foundation of China[grant number 82270544]+2 种基金the Sixth Affiliated Hospital“Jie Bang Gua Shuai”Program[grant number 2022JBGS06]the Science and Technology Program of Guangzhou,China[grant number SL2022B03J00237]the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases[grant number 2020B1111170004].
文摘Background:The genetic variant of tumor necrosis factor superfamily member 15(TNFSF15)is associated with Crohn’s disease(CD)and the development of intestinal fibrosis and stricturing.We aimed to investigate its predictive role in disease progression and the impact of ileal fibrosis-associated protein expression in Chinese patients with CD.Methods:We genotyped the single nucleotide polymorphism rs6478109 within the TNFSF15 gene in 428 CD patients and 450 health controls to assess its association with CD.Genotype-phenotype correlation analyses were performed.Mucosal samples from non-diseased terminal ileum were analyzed for TL1A and fibrosis-associated protein expression using western blot and immunohistochemistry.Results:The G allele frequency of rs6478109 was significantly higher among CD patients compared with health controls(63.3%vs.46.7%,P<0.001).Patients with GG genotype were more predisposed to develop the stricturing phenotype,compared with those with AA?AG genotypes with a hazard ratio of 1.426(95%confidence interval:1.029-1.977,P=0.033).This trend was similarly observed in patients utilizing biological agents,with a hazard ratio of 4.396(95%confidence interval:1.780-10.854,P=0.001).Furthermore,increased TL1A,pro-fibrotic proteins,and TGFβ1/Smad3 pathway activation were observed in non-diseased ileal mucosa of patients with GG genotype compared with those with AA genotype.Conclusions:The TNFSF15 risk genotype GG could promote the expression of pro-fibrotic proteins and may serve as a predictor for stricturing CD.
基金Supported by The Broad Foundation grant,No. IBD-0207R
文摘Inflammatory bowel disease is a group of diseases that includes Crohn＇s disease （CD） and ulcerative colitis. CD is characterized as a chronic inflammatory disease of the gastrointestinal tract, ranging from the mouth to the anus. Although there are gross pathological and histological similarities between CD and Johne＇s dis- ease of cattle, the cause of CD remains controversial. It is vital to understand fully the cause of this disease because it affects approximately 500 000 people in North America and Europe. It ranges from 27 to 48 cases per 100 000 people. There are many theories on the cause of CD ranging from possible association with environmental factors including microorganisms to imbalance in the intestinal normal flora of the pa- tients. Regardless of the environmental trigger, there is strong evidence that a genetic disposition is a major key in acquiring CD. Many studies have proven the link between mutations in the ATG16L, NOD2/CARD15, IBDS, CTLA4, TNFSF15 and IL23R genes, and CD. The purpose of this review is to examine all genetic aspects and theories of CD, including up to date multiple popu- lation studies performed worldwide.
