Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,hav...Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,have been found to participate in the progression of MASLD.Sodium butyrate(NaB),one of the most important SCFAs,shows therapeutic potentials in MASLD and its mechanisms have not been fully understood.The present study aimed to investigate the effects of NaB on metabolic dysfunction-associated steatohepatitis(MASH)associated fibrosis as well as the underlying mechanisms.Methods:Male Sprague-Dawley rats were randomly assigned to three groups:(i)control group,stan-dard chow for 24 weeks;(ii)HFD group,high-fat and high-cholesterol diet(HFD)for 24 weeks;and(iii)HFD+NaB group,HFD for 24 weeks and NaB gavage for the last 16 weeks.Body weight,liver index(liver weight/body weight×100%),serum parameters,and liver histology were analyzed to evaluate MASH and fibrosis severity.AML12,RAW264.7 and LX2 cell lines were used for in vitro study.Results:Compared to MASH rats with fibrosis induced by 24-week HFD,NaB intervention alleviated the degree of hepatic steatosis,inflammation,hepatocyte ballooning,and fibrosis.Further mechanistic study showed that NaB supplementation significantly decreased miR-155-5p level in the liver and the serum of MASH rats,and the inhibition effects of miR-155-5p on suppressor of cytokine signaling 1(SOCS1)in both hepatocytes and hepatic stellate cells(HSCs)were blunted when they were treated with NaB.Fur-thermore,NaB also significantly decreased the production of platelet-derived growth factor-BB(PDGF-BB),a pro-fibrotic mediator,in hepatocytes.NaB treatment on AML12 cells markedly impaired the prolifera-tion ability of co-cultured LX2 cells.Moreover,NaB intervention or miR-155-5p mimics also interferes extracellular regulated protein kinases signaling in LX2 cells.Conclusions:NaB intervention inhibited HSCs activation via miR-155-5p/SOCS1/PDGF signaling pathway and consequently relieved fibrosis in MASH rats.NaB might be a potential agent for the treatment of fibrosis in patients with MASH.展开更多
文摘目的:探讨基于微小核糖核酸(micrornas,miR)-221-3p、miR-155-5p及英国胸科协会改良肺炎(confusion,uremia,respiratory,BP,age 65years,CURB-65)评分构建的Nomogram预测模型对重症肺炎(severe pneumonia,SP)预后不良的预测价值。方法:前瞻性选取2021年1月至2024年6月宜春市人民医院收治的439例SP患者,按7:3比例随机分为建模组(n=307)与验证组(n=132)。治疗前检测患者血清miR-221-3p、miR-155-5p水平,并使用CURB-65得分进行评估。观察患者住院28 d内预后情况,根据28 d内预后情况将SP患者分为死亡组与存活组。采用Lasso回归分析SP患者预后不好的影响因素,多元素Logistic回归分析SP预后不良的危险因素。构建SP患者预后不良Nomogram预测模型,并采用受试者工作特征(receiver operating characteristic,ROC)曲线评估Nomogram模型对SP预后不良的预测效能。结果:建模组、验证组死亡率分别为29.32%(90/307)、28.79%(38/132),两组死亡率以及临床资料比较无统计学差异(P>0.05)。建模、验证人群中死亡组的年龄、肺部基础疾病比例、肺炎严重指数(pneumonia severity index,PSI)评分、急性生理学和慢性健康状况评分系统Ⅱ(Acute Physiology and Chronic Health EvaluationⅡ,APACHEⅡ)评分、CURB-65评分、血清miR-221-3p、miR-155-5p、C反应蛋白(C-reactive protein,CRP)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、降钙素原(procalcitonin,PCT)指标均高于存活组(P<0.05)。Logistic多因素回归分析显示高龄、高APACHEⅡ评分、miR-221-3p高表达、miR-155-5p高表达、高CURB-65评分是SP预后不良的危险因素(P<0.05)。构建的SP预后不良Nomogram预测模型对SP预后不良的曲线下面积(area under the curve,AUC)达0.824,具有良好的预测效能。结论:miR-221-3p高表达、miR-155-5p高表达、高CURB-65评分、高龄、高APACHEⅡ评分是SP患者预后不良的危险因素,基于上述因素构建的Nomogram预测模型对SP预后不良的预测价值较高。
基金supported by grants from the National Natural Science Foundation of China(81873565 and 81900507).
文摘Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,have been found to participate in the progression of MASLD.Sodium butyrate(NaB),one of the most important SCFAs,shows therapeutic potentials in MASLD and its mechanisms have not been fully understood.The present study aimed to investigate the effects of NaB on metabolic dysfunction-associated steatohepatitis(MASH)associated fibrosis as well as the underlying mechanisms.Methods:Male Sprague-Dawley rats were randomly assigned to three groups:(i)control group,stan-dard chow for 24 weeks;(ii)HFD group,high-fat and high-cholesterol diet(HFD)for 24 weeks;and(iii)HFD+NaB group,HFD for 24 weeks and NaB gavage for the last 16 weeks.Body weight,liver index(liver weight/body weight×100%),serum parameters,and liver histology were analyzed to evaluate MASH and fibrosis severity.AML12,RAW264.7 and LX2 cell lines were used for in vitro study.Results:Compared to MASH rats with fibrosis induced by 24-week HFD,NaB intervention alleviated the degree of hepatic steatosis,inflammation,hepatocyte ballooning,and fibrosis.Further mechanistic study showed that NaB supplementation significantly decreased miR-155-5p level in the liver and the serum of MASH rats,and the inhibition effects of miR-155-5p on suppressor of cytokine signaling 1(SOCS1)in both hepatocytes and hepatic stellate cells(HSCs)were blunted when they were treated with NaB.Fur-thermore,NaB also significantly decreased the production of platelet-derived growth factor-BB(PDGF-BB),a pro-fibrotic mediator,in hepatocytes.NaB treatment on AML12 cells markedly impaired the prolifera-tion ability of co-cultured LX2 cells.Moreover,NaB intervention or miR-155-5p mimics also interferes extracellular regulated protein kinases signaling in LX2 cells.Conclusions:NaB intervention inhibited HSCs activation via miR-155-5p/SOCS1/PDGF signaling pathway and consequently relieved fibrosis in MASH rats.NaB might be a potential agent for the treatment of fibrosis in patients with MASH.
