目的观察血清C1q肿瘤坏死因子相关蛋白1(CTRP1)、成纤维细胞生长因子21(FGF21)和人血管生成素样蛋白3(ANGPTL3)水平在2型糖尿病大血管病变中的诊断价值。方法选取2020年1月至2022年6月在该院诊治的165例2型糖尿病患者作为2型糖尿病组,...目的观察血清C1q肿瘤坏死因子相关蛋白1(CTRP1)、成纤维细胞生长因子21(FGF21)和人血管生成素样蛋白3(ANGPTL3)水平在2型糖尿病大血管病变中的诊断价值。方法选取2020年1月至2022年6月在该院诊治的165例2型糖尿病患者作为2型糖尿病组,根据患者是否合并大血管病变分为大血管病变组(57例)和单纯糖尿病组(108例),另选取同期该院75例健康体检者作为健康对照组。采用单因素和多因素分析2型糖尿病发生大血管病变的影响因素,以及血清CTRP1、FGF21和ANGPTL3水平在2型糖尿病发生大血管病变中的诊断价值。结果2型糖尿病组血清CTRP1、FGF21和ANGPTL3水平均明显高于健康对照组,差异均有统计学意义(P<0.05),并且随着糖尿病控制程度升高而降低。大血管病变组餐后2 h血糖(2 h PG)、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、颈动脉内膜中层厚度(IMT)、CTRP1、FGF21和ANGPTL3水平均明显高于单纯糖尿病组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,2 h PG、TG、颈动脉IMT、CTRP1、FGF21和ANGPTL3水平升高是发生大血管病变的独立危险因素(P<0.05)。血清CTRP1、FGF21和ANGPTL3水平在2型糖尿病发生大血管病变中具有较高的诊断效能,3项指标联合检测的灵敏度为68.4%,特异度为97.2%,受试者工作特征曲线下面积为0.897,明显高于CTRP1(Z=3.152,P=0.002)、FGF21(Z=3.755,P<0.001)和ANGPTL3(Z=4.410,P<0.001)单项检测。结论血清CTRP1、FGF21和ANGPTL3是2型糖尿病的重要监测指标,其水平升高是发生大血管病变的独立危险因素,3项指标联合检测有助于提高对2型糖尿病大血管病变的诊断效能。展开更多
Objective:To determine the relationship between human fibroblast growth factor 21(FGF21)and thyroid stimulating hormone(TSH)by testing the level of FGF21,lipid metabolism,and car-bohydrate metabolism-related indices,a...Objective:To determine the relationship between human fibroblast growth factor 21(FGF21)and thyroid stimulating hormone(TSH)by testing the level of FGF21,lipid metabolism,and car-bohydrate metabolism-related indices,as well as the level of TSH,among metabolic syndrome-free patients with normal physical examination results.Methods:An enzyme-linked immunosorbent assay(ELISA)was used to test the levels of serum FGF21 and free fatty acids(FFA)in metabolic syndrome-free patients with normal physi-cal examination results,and electrochemiluminescence(ECLIA)was used to measure TSH,thy-roglobulin antibodies(TGAbs),and thyroid peroxidase antibody(TPOAb)levels.Results:Three hundred fifty-six metabolic syndrome-free patients(116 males and 240 females;average age,43±13 years)with normal physical examination results were enrolled.Among the pa-tients with normal physical examination results,FGF21 had a weak relationship with obesity indices,such as the waist circumference(r=0.110,P=0.038),the waist-to-hip ratio(r=0.119,P=0.025),and the triglycerides level(TG;r=0.302,P=0.000),and a weak relationship with blood lipid levels,such as total cholesterol(TCHO;r=0.113,P=0.012)and low-density lipoprotein-cholesterol(LDL-C;r=0.175,P=0.001),but no relationship with TSH(r=-0.023,P=0.666).In addition,the FGF21 levels in thyroid autoantibody-positive and-negative groups were not significantly different.Conclusion:Among the metabolic syndrome-free patients with normal physical examina-tion results,FGF21 has no apparent relationship with TSH or thyroid autoimmunity.展开更多
Objective: To investigate the effects of Ganoderma lucidum polysaccharides(GL-PS) on human fibroblasts and skin wound healing in Kunming male mice and to explore the putative molecular mechanism. Methods: Primary huma...Objective: To investigate the effects of Ganoderma lucidum polysaccharides(GL-PS) on human fibroblasts and skin wound healing in Kunming male mice and to explore the putative molecular mechanism. Methods: Primary human skin fibroblasts were cultured. The viability of fibroblasts treated with 0, 10, 20, 40, 80, and 160 μg/mL of GL-PS, respectively were detected by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-Htetrazolium bromide(MTT). The migration ability of fibroblasts treated with 0, 10, 20, and 40 μg/mL of GL-PS were measured by transwell assay. The secretion of the C-terminal peptide of procollagen type Ⅰ(CICP) and transforming growth factor-β1(TGF-β1) in the cell supernatant was tested by enzyme-linked immunosorbent assay. The expression of β-catenin was detected by Western blot. Furthermore, the Kunming mouse model with full-layer skin resection trauma was established, and was treated with 10, 20, and 40 mg/mL of GL-PS, respectively as external use. The size of the wound was measured daily, complete healing time in each group was recorded and the percentage of wound contraction was calculated. Results: Compared with the control group, 10, 20, and 40 μg/mL of GL-PS significantly increased the viability of fibroblasts, promoted the migration ability of fibroblasts, and up-regulated the expressions of CICP and TGF-β1 in fibroblasts(P<0.05 or P<0.01). The expression of β-catenin in fibroblasts treated with 20 and 40 μg/mL of GL-PS was significantly higher than that of the control group(P<0.01). Furthermore, after external use of 10, 20, and 40 mg/mL of GL-PS, the rates of wound healing in mice were significantly higher and the wound healing time was significantly less than the control group(P<0.05 or P<0.01). Conclusion: A certain concentration of GL-PS may promote wound healing via activation of the Wnt/β-catenin signaling pathway and up-regulation of TGF-β1, which might serve as a promising source of skin wound healing.展开更多
BACKGROUND Sodium glucose cotransporter 2(SGLT2)inhibitors are newly developed oral antidiabetic drugs.SGLT2 is primarily expressed in the kidneys and reabsorbs approximately 90%of the glucose filtered by the renal gl...BACKGROUND Sodium glucose cotransporter 2(SGLT2)inhibitors are newly developed oral antidiabetic drugs.SGLT2 is primarily expressed in the kidneys and reabsorbs approximately 90%of the glucose filtered by the renal glomeruli.SGLT2 inhibitors lower glucose levels independently of insulin action by facilitating urinary glucose excretion.The SGLT2 inhibitor ipragliflozin has reportedly improved liver steatosis in animal models and clinical studies.However,the mechanisms by which SGLT2 inhibitors improve liver steatosis are not fully understood.AIM To investigate the ameliorative effects of ipragliflozin on liver steatosis and the mechanisms of these effects in obese mice.METHODS We analyzed 8-wk-old male obese(ob/ob)mice that were randomly divided into a group receiving a normal chow diet and a group receiving a normal chow diet supplemented with ipragliflozin(3 mg/kg or 10 mg/kg)for 4 wk.We also analyzed their lean sex-matched littermates receiving a normal chow diet as another control group. Body weight and liver weight were evaluated, and liverhistology, immunoblotting, and reverse transcription-polymerase chain reactionanalyses were performed.RESULTSHepatic lipid accumulation was significantly ameliorated in ob/ob mice treatedwith 10 mg/kg ipragliflozin compared to untreated ob/ob mice irrespective ofbody weight changes. Ipragliflozin had no appreciable effects on hepatic oxidativestress-related gene expression levels or macrophage infiltration, but significantlyreduced hepatic interleukin-1β (IL-1β) mRNA expression levels. Ipragliflozinincreased both the mRNA and protein expression levels of sirtuin 1 (SIRT1) in theliver. The hepatic mRNA levels of peroxisome proliferator-activated receptor γcoactivator 1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα),and fibroblast growth factor-21 (FGF21) were also significantly higher inipragliflozin-treated ob/ob mice than in untreated ob/ob mice.CONCLUSIONOur study suggests that the liver steatosis-ameliorating effects of ipragliflozin inob/ob mice may be mediated partly by hepatic SIRT1 signaling, possibly throughthe PGC-1α/PPARα-FGF21 pathway.展开更多
Background:Our previous work demonstrated that Gekko sulfated glycopeptide extracted from the Chinese gecko Shou gong(Gekko swinhonis Guenther)could inhibit tumor growth by regulating basic fibroblast growth factor.Ho...Background:Our previous work demonstrated that Gekko sulfated glycopeptide extracted from the Chinese gecko Shou gong(Gekko swinhonis Guenther)could inhibit tumor growth by regulating basic fibroblast growth factor.However,basic fibroblast growth factor has opposing effects on growth in breast and liver cancers.Direct effects and mechanisms of Gekko sulfated glycopeptide on tumor growth remain unclear and are ripe for further exploration.Methods:Differential regulation by Gekko sulfated glycopeptide and bFGF were studied in established human breast cancer MCF-7 cells and hepatocarcinoma HepG2 cells.Cell proliferation was evaluated with a Trypan blue exclusion assay.Cell cycle phases were measured by flow cytometry.Basic fibroblast growth factor,transforming growth factor-β1,and p21WAF1/CIP1 mRNA and protein expression levels were detected by real-time PCR(mRNA)and ELISA(protein).Changes in phosphorylated extracellular signal-regulated kinase levels were analyzed by Western blot.Results:Data indicated that Gekko sulfated glycopeptide inhibited the proliferation of HepG2 cells(P<0.001)and also blocked basic fibroblast growth factor-stimulated proliferation of these cells(P=0.001).Gekko sulfated glycopeptide was shown to increase transforming growth factor-β1 and p21WAF1/CiP1 expression(P<0.01)and partially compensate for reductions therein induced by basic fibroblast growth factor.Conversely,in MCF-7 cells,Gekko sulfated glycopeptide alone had no observable effect on transforming growth factor-β1 and p21WAF1/CiP1 expression.Gekko sulfated glycopeptide did,however,enhance basic fibroblast growth factor-induced inhibition of cell proliferation and transforming growth factor-β1 and p21WAF1/CiP1 expression in the MCF-7 cells(P=0.001,P<0.01,P<0.01,respectively).Gekko sulfated glycopeptide was shown to suppress basic fibroblast growth factor secretion in both HepG2 and MCF-7 cell lines(P<0.05 and P<0.01,respectively)and inhibited extracellular signal-regulated kinase 1/2 phosphorylation facilitated by basic fibroblast growth factor.Gekko sulfated glycopeptide alone decreased phosphorylated extracellular signal-regulated kinase in HepG2 cells but did not visibly affect phosphorylated extracellular signal-regulated kinase levels in MCF-7 cells.Conclusions:Gekko sulfated glycopeptide,a basic fibroblast growth factor inhibitor,differentially regulates growth in different cancer cell lines,and these differences may be determined by the opposing effects of basic fibroblast growth factor on transforming growth factor-β1 and p21WAF1/CiP1 levels in breast and liver cancer cells.展开更多
文摘目的观察血清C1q肿瘤坏死因子相关蛋白1(CTRP1)、成纤维细胞生长因子21(FGF21)和人血管生成素样蛋白3(ANGPTL3)水平在2型糖尿病大血管病变中的诊断价值。方法选取2020年1月至2022年6月在该院诊治的165例2型糖尿病患者作为2型糖尿病组,根据患者是否合并大血管病变分为大血管病变组(57例)和单纯糖尿病组(108例),另选取同期该院75例健康体检者作为健康对照组。采用单因素和多因素分析2型糖尿病发生大血管病变的影响因素,以及血清CTRP1、FGF21和ANGPTL3水平在2型糖尿病发生大血管病变中的诊断价值。结果2型糖尿病组血清CTRP1、FGF21和ANGPTL3水平均明显高于健康对照组,差异均有统计学意义(P<0.05),并且随着糖尿病控制程度升高而降低。大血管病变组餐后2 h血糖(2 h PG)、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、颈动脉内膜中层厚度(IMT)、CTRP1、FGF21和ANGPTL3水平均明显高于单纯糖尿病组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,2 h PG、TG、颈动脉IMT、CTRP1、FGF21和ANGPTL3水平升高是发生大血管病变的独立危险因素(P<0.05)。血清CTRP1、FGF21和ANGPTL3水平在2型糖尿病发生大血管病变中具有较高的诊断效能,3项指标联合检测的灵敏度为68.4%,特异度为97.2%,受试者工作特征曲线下面积为0.897,明显高于CTRP1(Z=3.152,P=0.002)、FGF21(Z=3.755,P<0.001)和ANGPTL3(Z=4.410,P<0.001)单项检测。结论血清CTRP1、FGF21和ANGPTL3是2型糖尿病的重要监测指标,其水平升高是发生大血管病变的独立危险因素,3项指标联合检测有助于提高对2型糖尿病大血管病变的诊断效能。
文摘Objective:To determine the relationship between human fibroblast growth factor 21(FGF21)and thyroid stimulating hormone(TSH)by testing the level of FGF21,lipid metabolism,and car-bohydrate metabolism-related indices,as well as the level of TSH,among metabolic syndrome-free patients with normal physical examination results.Methods:An enzyme-linked immunosorbent assay(ELISA)was used to test the levels of serum FGF21 and free fatty acids(FFA)in metabolic syndrome-free patients with normal physi-cal examination results,and electrochemiluminescence(ECLIA)was used to measure TSH,thy-roglobulin antibodies(TGAbs),and thyroid peroxidase antibody(TPOAb)levels.Results:Three hundred fifty-six metabolic syndrome-free patients(116 males and 240 females;average age,43±13 years)with normal physical examination results were enrolled.Among the pa-tients with normal physical examination results,FGF21 had a weak relationship with obesity indices,such as the waist circumference(r=0.110,P=0.038),the waist-to-hip ratio(r=0.119,P=0.025),and the triglycerides level(TG;r=0.302,P=0.000),and a weak relationship with blood lipid levels,such as total cholesterol(TCHO;r=0.113,P=0.012)and low-density lipoprotein-cholesterol(LDL-C;r=0.175,P=0.001),but no relationship with TSH(r=-0.023,P=0.666).In addition,the FGF21 levels in thyroid autoantibody-positive and-negative groups were not significantly different.Conclusion:Among the metabolic syndrome-free patients with normal physical examina-tion results,FGF21 has no apparent relationship with TSH or thyroid autoimmunity.
基金Supported by the Fundamental Research Funds for the Central Universities of Central South University(No.2017zzts235)
文摘Objective: To investigate the effects of Ganoderma lucidum polysaccharides(GL-PS) on human fibroblasts and skin wound healing in Kunming male mice and to explore the putative molecular mechanism. Methods: Primary human skin fibroblasts were cultured. The viability of fibroblasts treated with 0, 10, 20, 40, 80, and 160 μg/mL of GL-PS, respectively were detected by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-Htetrazolium bromide(MTT). The migration ability of fibroblasts treated with 0, 10, 20, and 40 μg/mL of GL-PS were measured by transwell assay. The secretion of the C-terminal peptide of procollagen type Ⅰ(CICP) and transforming growth factor-β1(TGF-β1) in the cell supernatant was tested by enzyme-linked immunosorbent assay. The expression of β-catenin was detected by Western blot. Furthermore, the Kunming mouse model with full-layer skin resection trauma was established, and was treated with 10, 20, and 40 mg/mL of GL-PS, respectively as external use. The size of the wound was measured daily, complete healing time in each group was recorded and the percentage of wound contraction was calculated. Results: Compared with the control group, 10, 20, and 40 μg/mL of GL-PS significantly increased the viability of fibroblasts, promoted the migration ability of fibroblasts, and up-regulated the expressions of CICP and TGF-β1 in fibroblasts(P<0.05 or P<0.01). The expression of β-catenin in fibroblasts treated with 20 and 40 μg/mL of GL-PS was significantly higher than that of the control group(P<0.01). Furthermore, after external use of 10, 20, and 40 mg/mL of GL-PS, the rates of wound healing in mice were significantly higher and the wound healing time was significantly less than the control group(P<0.05 or P<0.01). Conclusion: A certain concentration of GL-PS may promote wound healing via activation of the Wnt/β-catenin signaling pathway and up-regulation of TGF-β1, which might serve as a promising source of skin wound healing.
文摘BACKGROUND Sodium glucose cotransporter 2(SGLT2)inhibitors are newly developed oral antidiabetic drugs.SGLT2 is primarily expressed in the kidneys and reabsorbs approximately 90%of the glucose filtered by the renal glomeruli.SGLT2 inhibitors lower glucose levels independently of insulin action by facilitating urinary glucose excretion.The SGLT2 inhibitor ipragliflozin has reportedly improved liver steatosis in animal models and clinical studies.However,the mechanisms by which SGLT2 inhibitors improve liver steatosis are not fully understood.AIM To investigate the ameliorative effects of ipragliflozin on liver steatosis and the mechanisms of these effects in obese mice.METHODS We analyzed 8-wk-old male obese(ob/ob)mice that were randomly divided into a group receiving a normal chow diet and a group receiving a normal chow diet supplemented with ipragliflozin(3 mg/kg or 10 mg/kg)for 4 wk.We also analyzed their lean sex-matched littermates receiving a normal chow diet as another control group. Body weight and liver weight were evaluated, and liverhistology, immunoblotting, and reverse transcription-polymerase chain reactionanalyses were performed.RESULTSHepatic lipid accumulation was significantly ameliorated in ob/ob mice treatedwith 10 mg/kg ipragliflozin compared to untreated ob/ob mice irrespective ofbody weight changes. Ipragliflozin had no appreciable effects on hepatic oxidativestress-related gene expression levels or macrophage infiltration, but significantlyreduced hepatic interleukin-1β (IL-1β) mRNA expression levels. Ipragliflozinincreased both the mRNA and protein expression levels of sirtuin 1 (SIRT1) in theliver. The hepatic mRNA levels of peroxisome proliferator-activated receptor γcoactivator 1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα),and fibroblast growth factor-21 (FGF21) were also significantly higher inipragliflozin-treated ob/ob mice than in untreated ob/ob mice.CONCLUSIONOur study suggests that the liver steatosis-ameliorating effects of ipragliflozin inob/ob mice may be mediated partly by hepatic SIRT1 signaling, possibly throughthe PGC-1α/PPARα-FGF21 pathway.
基金This work was supported by grants from the New Century Excellent Talent(NCET-11-1068)and National Science Foundation of China(No.81173376).
文摘Background:Our previous work demonstrated that Gekko sulfated glycopeptide extracted from the Chinese gecko Shou gong(Gekko swinhonis Guenther)could inhibit tumor growth by regulating basic fibroblast growth factor.However,basic fibroblast growth factor has opposing effects on growth in breast and liver cancers.Direct effects and mechanisms of Gekko sulfated glycopeptide on tumor growth remain unclear and are ripe for further exploration.Methods:Differential regulation by Gekko sulfated glycopeptide and bFGF were studied in established human breast cancer MCF-7 cells and hepatocarcinoma HepG2 cells.Cell proliferation was evaluated with a Trypan blue exclusion assay.Cell cycle phases were measured by flow cytometry.Basic fibroblast growth factor,transforming growth factor-β1,and p21WAF1/CIP1 mRNA and protein expression levels were detected by real-time PCR(mRNA)and ELISA(protein).Changes in phosphorylated extracellular signal-regulated kinase levels were analyzed by Western blot.Results:Data indicated that Gekko sulfated glycopeptide inhibited the proliferation of HepG2 cells(P<0.001)and also blocked basic fibroblast growth factor-stimulated proliferation of these cells(P=0.001).Gekko sulfated glycopeptide was shown to increase transforming growth factor-β1 and p21WAF1/CiP1 expression(P<0.01)and partially compensate for reductions therein induced by basic fibroblast growth factor.Conversely,in MCF-7 cells,Gekko sulfated glycopeptide alone had no observable effect on transforming growth factor-β1 and p21WAF1/CiP1 expression.Gekko sulfated glycopeptide did,however,enhance basic fibroblast growth factor-induced inhibition of cell proliferation and transforming growth factor-β1 and p21WAF1/CiP1 expression in the MCF-7 cells(P=0.001,P<0.01,P<0.01,respectively).Gekko sulfated glycopeptide was shown to suppress basic fibroblast growth factor secretion in both HepG2 and MCF-7 cell lines(P<0.05 and P<0.01,respectively)and inhibited extracellular signal-regulated kinase 1/2 phosphorylation facilitated by basic fibroblast growth factor.Gekko sulfated glycopeptide alone decreased phosphorylated extracellular signal-regulated kinase in HepG2 cells but did not visibly affect phosphorylated extracellular signal-regulated kinase levels in MCF-7 cells.Conclusions:Gekko sulfated glycopeptide,a basic fibroblast growth factor inhibitor,differentially regulates growth in different cancer cell lines,and these differences may be determined by the opposing effects of basic fibroblast growth factor on transforming growth factor-β1 and p21WAF1/CiP1 levels in breast and liver cancer cells.
