Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disorder,accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota.Recently,accumulating evidence has supported a corr...Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disorder,accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota.Recently,accumulating evidence has supported a correlation between gut dysbiosis and CP development.However,whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear.Herein,an experimental CP was induced by repeated high-dose caerulein injections.The broad-spectrum antibiotics(ABX)and ABX targeting Gram-positive(G+)or Gram-negative bacteria(G-)were applied to explore the specific roles of these bacteria.Gut dysbiosis was observed in both mice and in CP patients,which was accompanied by a sharply reduced abundance for short-chain fatty acids(SCFAs)-producers,especially G+bacteria.Broad-spectrum ABX exacerbated the severity of CP,as evidenced by aggravated pancreatic fibrosis and gut dysbiosis,especially the depletion of SCFAs-producing G+bacteria.Additionally,depletion of SCFAs-producing G+bacteria rather than G-bacteria intensified CP progression independent of TLR4,which was attenuated by supplementation with exogenous SCFAs.Finally,SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching.The study supports a critical role for SCFAs-producing G+bacteria in CP.Therefore,modulation of dietary-derived SCFAs or G+SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.展开更多
目的探究大气臭氧(ozone,O3)长期暴露与我国中老年人群抑郁的关联,为预防和干预抑郁提供科学指导。方法在我国大气污染防治重点区域中选择16个省、自治区、直辖市的45个县、区作为研究现场,按照严格的调查社区选择原则和调查对象纳入标...目的探究大气臭氧(ozone,O3)长期暴露与我国中老年人群抑郁的关联,为预防和干预抑郁提供科学指导。方法在我国大气污染防治重点区域中选择16个省、自治区、直辖市的45个县、区作为研究现场,按照严格的调查社区选择原则和调查对象纳入标准进行随机抽样,选择8584名40~<90岁中老年人作为研究对象。采用统一编制的调查问卷收集调查对象的人口学特征、社会经济状况、疾病和症状信息,使用9条目患者健康问卷(Patient Health Questionnaire 9,PHQ-9)评估调查对象的抑郁患病情况。通过距离社区最近的空气质量监测国控站点数据估算调查前1年大气污染物平均浓度和调查前2年大气污染物滑动平均浓度,采用多因素Logistic回归分析模型探讨O3暴露与罹患抑郁的关联。结果纳入研究的8584名调查对象中,抑郁患病率为6.79%(583/8584)。Logistic回归分析模型显示,未发现O3长期暴露与抑郁患病风险有关,总体上看,调查前2年的O3滑动平均年均浓度对应的效应值最大(OR=1.04,95%CI:0.96~1.13,P=0.326),但无统计学意义;分层分析显示,与女性和不吸烟的调查对象相比,男性和现在吸烟的调查对象抑郁患病与O3暴露的关联更强,且组间差异具有统计学意义(均有P<0.05);空气动力学直径<2.5μm的颗粒物(particulate matter smaller than 2.5μm in aerodynamic diameter,PM2.5)浓度和气温对抑郁患病与O3暴露的关联存在修饰作用,低PM2.5浓度、较高气温地区抑郁患病与O3暴露关联更强。结论本研究发现男性人群、吸烟人群以及生活在PM2.5浓度较低和年均气温较高地区的人群中,O3暴露与抑郁患病风险存在关联。展开更多
Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons.The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in mus...Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons.The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in muscle to chronic cold exposure via Min pig models(cold adaptation)and Yorkshire pig models(non-cold adaptation).Furthermore,this study explored the beneficial effects of glucose supplementation on small intestinal amino acid transport and amino acid pool in muscle of cold-exposed Yorkshire pigs.Min pigs(Exp.1)and Yorkshire pigs(Exp.2)were divided into a control group(17℃,n=6)and chronic cold exposure group(7℃,n=6),respectively.Twelve Yorkshire pigs(Exp.3)were divided into a cold control group and cold glucose supplementation group(8℃).The results showed that chronic cold exposure inhibited peptide transporter protein 1(PepT1)and excitatory amino acid transporter 3(EAAT3)expression in ileal mucosa and cationic amino acid transporter-1(CAT-1)in the jejunal mucosa of Yorkshire pigs(P<0.05).In contrast,CAT-1,PepT1 and EAAT3 expression was enhanced in the duodenal mucosa of Min pigs(P<0.05).Branched amino acids(BCAA)in the muscle of Yorkshire pigs were consumed by chronic cold exposure,accompanied by increased muscle RING-finger protein-1(MuRF1)and muscle atrophy F-box(atrogin-1)expression(P<0.05).More importantly,reduced concentrations of dystrophin were detected in the muscle of Yorkshire pigs(P<0.05).However,glycine concentration in the muscle of Min pigs was raised(P<0.05).In the absence of interaction between chronic cold exposure and glucose supplementation,glucose supplementation improved CAT-1 expression in the jejunal mucosa and PepT1 expression in the ileal mucosa of cold-exposed Yorkshire pigs(P<0.05).It also improved BCAA and inhibited MuRF1 and atrogin-1 expression in muscle(P<0.05).Moreover,dystrophin concentration was improved by glucose supplementation(P<0.05).In summary,chronic cold exposure inhibits amino acid absorption in the small intestine,depletes BCAA and promotes protein degra展开更多
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.82070666,82122068)the Natural Science Foundation for Distinguished Young Scholars of Jiangsu Province(Grant No.BK20200026,China)+4 种基金the Collaborative Innovation Center of Food Safety and Quality Control of Jiangsu Province,the Fundamental Research Funds for the Central Universities(Grant Nos.JUSRP221037,JUSRP22007,China)the China Postdoctoral Science Foundation(Grant No.2022M721366)the Excellent Postdoctoral Program of Jiangsu Province(Grant No.2023ZB168,China)Wuxi City’s first“double hundred”young and middle-aged medical and health talents(Grant No:BJ2020045,China)Wuxi Social Development Science and Technology Demonstration Project(Grant No:N20201003,China)。
文摘Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disorder,accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota.Recently,accumulating evidence has supported a correlation between gut dysbiosis and CP development.However,whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear.Herein,an experimental CP was induced by repeated high-dose caerulein injections.The broad-spectrum antibiotics(ABX)and ABX targeting Gram-positive(G+)or Gram-negative bacteria(G-)were applied to explore the specific roles of these bacteria.Gut dysbiosis was observed in both mice and in CP patients,which was accompanied by a sharply reduced abundance for short-chain fatty acids(SCFAs)-producers,especially G+bacteria.Broad-spectrum ABX exacerbated the severity of CP,as evidenced by aggravated pancreatic fibrosis and gut dysbiosis,especially the depletion of SCFAs-producing G+bacteria.Additionally,depletion of SCFAs-producing G+bacteria rather than G-bacteria intensified CP progression independent of TLR4,which was attenuated by supplementation with exogenous SCFAs.Finally,SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching.The study supports a critical role for SCFAs-producing G+bacteria in CP.Therefore,modulation of dietary-derived SCFAs or G+SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.
文摘目的探究大气臭氧(ozone,O3)长期暴露与我国中老年人群抑郁的关联,为预防和干预抑郁提供科学指导。方法在我国大气污染防治重点区域中选择16个省、自治区、直辖市的45个县、区作为研究现场,按照严格的调查社区选择原则和调查对象纳入标准进行随机抽样,选择8584名40~<90岁中老年人作为研究对象。采用统一编制的调查问卷收集调查对象的人口学特征、社会经济状况、疾病和症状信息,使用9条目患者健康问卷(Patient Health Questionnaire 9,PHQ-9)评估调查对象的抑郁患病情况。通过距离社区最近的空气质量监测国控站点数据估算调查前1年大气污染物平均浓度和调查前2年大气污染物滑动平均浓度,采用多因素Logistic回归分析模型探讨O3暴露与罹患抑郁的关联。结果纳入研究的8584名调查对象中,抑郁患病率为6.79%(583/8584)。Logistic回归分析模型显示,未发现O3长期暴露与抑郁患病风险有关,总体上看,调查前2年的O3滑动平均年均浓度对应的效应值最大(OR=1.04,95%CI:0.96~1.13,P=0.326),但无统计学意义;分层分析显示,与女性和不吸烟的调查对象相比,男性和现在吸烟的调查对象抑郁患病与O3暴露的关联更强,且组间差异具有统计学意义(均有P<0.05);空气动力学直径<2.5μm的颗粒物(particulate matter smaller than 2.5μm in aerodynamic diameter,PM2.5)浓度和气温对抑郁患病与O3暴露的关联存在修饰作用,低PM2.5浓度、较高气温地区抑郁患病与O3暴露关联更强。结论本研究发现男性人群、吸烟人群以及生活在PM2.5浓度较低和年均气温较高地区的人群中,O3暴露与抑郁患病风险存在关联。
基金This work was supported by the National Key R&D Program of China(2021YFD1300403)the Major Program of Heilongjiang Province of China(2021ZX12B08-02).
文摘Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons.The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in muscle to chronic cold exposure via Min pig models(cold adaptation)and Yorkshire pig models(non-cold adaptation).Furthermore,this study explored the beneficial effects of glucose supplementation on small intestinal amino acid transport and amino acid pool in muscle of cold-exposed Yorkshire pigs.Min pigs(Exp.1)and Yorkshire pigs(Exp.2)were divided into a control group(17℃,n=6)and chronic cold exposure group(7℃,n=6),respectively.Twelve Yorkshire pigs(Exp.3)were divided into a cold control group and cold glucose supplementation group(8℃).The results showed that chronic cold exposure inhibited peptide transporter protein 1(PepT1)and excitatory amino acid transporter 3(EAAT3)expression in ileal mucosa and cationic amino acid transporter-1(CAT-1)in the jejunal mucosa of Yorkshire pigs(P<0.05).In contrast,CAT-1,PepT1 and EAAT3 expression was enhanced in the duodenal mucosa of Min pigs(P<0.05).Branched amino acids(BCAA)in the muscle of Yorkshire pigs were consumed by chronic cold exposure,accompanied by increased muscle RING-finger protein-1(MuRF1)and muscle atrophy F-box(atrogin-1)expression(P<0.05).More importantly,reduced concentrations of dystrophin were detected in the muscle of Yorkshire pigs(P<0.05).However,glycine concentration in the muscle of Min pigs was raised(P<0.05).In the absence of interaction between chronic cold exposure and glucose supplementation,glucose supplementation improved CAT-1 expression in the jejunal mucosa and PepT1 expression in the ileal mucosa of cold-exposed Yorkshire pigs(P<0.05).It also improved BCAA and inhibited MuRF1 and atrogin-1 expression in muscle(P<0.05).Moreover,dystrophin concentration was improved by glucose supplementation(P<0.05).In summary,chronic cold exposure inhibits amino acid absorption in the small intestine,depletes BCAA and promotes protein degra
