BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit t...BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400μmol/L cobalt nanoparticles and 25μmol/L deferiprone),the deferiprone group(25μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P<0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factorα,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factorα,interleukin-1β,and interleukin-6)significantly decreased(P<0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P<0.05),while deferiprone inhibited this effect(P<0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.展开更多
目的探讨人胰升血糖素样肽-1(GLP-1)类似物利拉鲁肽对2型糖尿病患者血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、人高敏C反应蛋白(hs-CRP)及脂联素的影响。方法选择本院住院的2型糖尿病患者40例作为实验组,健康体检者40例作为对照组...目的探讨人胰升血糖素样肽-1(GLP-1)类似物利拉鲁肽对2型糖尿病患者血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、人高敏C反应蛋白(hs-CRP)及脂联素的影响。方法选择本院住院的2型糖尿病患者40例作为实验组,健康体检者40例作为对照组,实验组改用利拉鲁肽治疗24周。分别于治疗前、治疗第12周、第24周测空腹血糖(FPG)、餐后2 h血糖(2 h PG)、空腹胰岛素(FINS)、糖化血红蛋白(Hb A1c)、hs-CRP、IL-6、TNF-α及脂联素,计算胰岛素抵抗指数(HOMA-IR)。结果利拉鲁肽治疗后,FPG、2 h PG、HOMA-IR、IL-6、TNF-α、hs-CRP显著下降(P<0.01),Hb A1c逐步降低(P<0.05),FINS、脂联素显著升高(P<0.01)。结论人GLP-1类似物可使2型糖尿病患者血清IL-6、TNF-α、hs-CRP浓度降低、脂联素浓度升高,从而抑制炎症反应,在一定程度上延缓2型糖尿病及其并发症的发生、发展。展开更多
目的以复合终点达标率为评价指标,比较利拉鲁肽与预混胰岛素治疗新诊断2型糖尿病患者的短期疗效。方法选取2012年1月-2013年5月该院新诊断2型糖尿病患者80例,按随机数字表随机分为利拉鲁肽组(n=40)和预混胰岛素组(n=40),分别给予利拉鲁...目的以复合终点达标率为评价指标,比较利拉鲁肽与预混胰岛素治疗新诊断2型糖尿病患者的短期疗效。方法选取2012年1月-2013年5月该院新诊断2型糖尿病患者80例,按随机数字表随机分为利拉鲁肽组(n=40)和预混胰岛素组(n=40),分别给予利拉鲁肽和预混胰岛素治疗,疗程12周。分别于0周及12周测收缩压(SBP)、舒张压(DBP)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(Hb A1c),计算体重指数(BMI),记录低血糖发生情况。以Hb A1c<7.0%、血压<130/80 mm Hg、TG<1.7 mmol/L、LDL-C<2.6 mmol/L、BMI<24 kg/m2,以及没有发生低血糖事件构建复合终点达标标准。结果治疗前两组各项指标比较差异均无统计学意义(P>0.05);治疗后两组BMI、FPG、2 h PBG、Hb A1c均显著下降(P<0.01),利拉鲁肽组TC亦显著下降(P<0.05)。两组SBP、DBP、TG、LDL-C及预混胰岛素组TC的差异均无统计学意义(P>0.05);两组间BMI、SBP、DBP、TG、TC、LDL-c、FPG、2 h PBG、Hb A1c差异均无统计学意义(P>0.05)。利拉鲁肽组低血糖发生率为2.6%,显著低于预混胰岛素组(P<0.05),复合终点达标率为41%,显著高于预混胰岛素组(P<0.05)。结论以复合终点达标率为评价指标,利拉鲁肽治疗新诊断2型糖尿病患者的短期疗效显著优于预混胰岛素。展开更多
文摘BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400μmol/L cobalt nanoparticles and 25μmol/L deferiprone),the deferiprone group(25μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P<0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factorα,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factorα,interleukin-1β,and interleukin-6)significantly decreased(P<0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P<0.05),while deferiprone inhibited this effect(P<0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.
文摘目的探讨人胰升血糖素样肽-1(GLP-1)类似物利拉鲁肽对2型糖尿病患者血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、人高敏C反应蛋白(hs-CRP)及脂联素的影响。方法选择本院住院的2型糖尿病患者40例作为实验组,健康体检者40例作为对照组,实验组改用利拉鲁肽治疗24周。分别于治疗前、治疗第12周、第24周测空腹血糖(FPG)、餐后2 h血糖(2 h PG)、空腹胰岛素(FINS)、糖化血红蛋白(Hb A1c)、hs-CRP、IL-6、TNF-α及脂联素,计算胰岛素抵抗指数(HOMA-IR)。结果利拉鲁肽治疗后,FPG、2 h PG、HOMA-IR、IL-6、TNF-α、hs-CRP显著下降(P<0.01),Hb A1c逐步降低(P<0.05),FINS、脂联素显著升高(P<0.01)。结论人GLP-1类似物可使2型糖尿病患者血清IL-6、TNF-α、hs-CRP浓度降低、脂联素浓度升高,从而抑制炎症反应,在一定程度上延缓2型糖尿病及其并发症的发生、发展。
文摘目的以复合终点达标率为评价指标,比较利拉鲁肽与预混胰岛素治疗新诊断2型糖尿病患者的短期疗效。方法选取2012年1月-2013年5月该院新诊断2型糖尿病患者80例,按随机数字表随机分为利拉鲁肽组(n=40)和预混胰岛素组(n=40),分别给予利拉鲁肽和预混胰岛素治疗,疗程12周。分别于0周及12周测收缩压(SBP)、舒张压(DBP)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(Hb A1c),计算体重指数(BMI),记录低血糖发生情况。以Hb A1c<7.0%、血压<130/80 mm Hg、TG<1.7 mmol/L、LDL-C<2.6 mmol/L、BMI<24 kg/m2,以及没有发生低血糖事件构建复合终点达标标准。结果治疗前两组各项指标比较差异均无统计学意义(P>0.05);治疗后两组BMI、FPG、2 h PBG、Hb A1c均显著下降(P<0.01),利拉鲁肽组TC亦显著下降(P<0.05)。两组SBP、DBP、TG、LDL-C及预混胰岛素组TC的差异均无统计学意义(P>0.05);两组间BMI、SBP、DBP、TG、TC、LDL-c、FPG、2 h PBG、Hb A1c差异均无统计学意义(P>0.05)。利拉鲁肽组低血糖发生率为2.6%,显著低于预混胰岛素组(P<0.05),复合终点达标率为41%,显著高于预混胰岛素组(P<0.05)。结论以复合终点达标率为评价指标,利拉鲁肽治疗新诊断2型糖尿病患者的短期疗效显著优于预混胰岛素。
