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4-苯基丁酸缓解利培酮诱导肥胖的作用及机制研究
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作者 葛笑妹 段燈 +3 位作者 李素玉 谢铭辉 樊欣睿 何梦 《中国医院药学杂志》 北大核心 2026年第6期615-622,共8页
目的:探讨内质网应激抑制剂4-苯基丁酸(4-phenylbutyric acid,4-PBA)对利培酮(ris)诱导的药源性肥胖的改善作用及其分子机制。方法:建立雌性SD大鼠利培酮肥胖模型(0.3 mg·kg^(-1)·d^(-1),40 d),建模成功后随机分为利培酮单药... 目的:探讨内质网应激抑制剂4-苯基丁酸(4-phenylbutyric acid,4-PBA)对利培酮(ris)诱导的药源性肥胖的改善作用及其分子机制。方法:建立雌性SD大鼠利培酮肥胖模型(0.3 mg·kg^(-1)·d^(-1),40 d),建模成功后随机分为利培酮单药组、高剂量4-PBA联合给药组(ris+4-PBAh,1.0 g·kg^(-1)·d^(-1))及低剂量4-PBA联合给药组(ris+4-PBAl,0.5 g·kg^(-1)·d^(-1));对照组分为空白对照组和4-PBA药物对照组,各组联合4-PBA给药30 d。期间动态监测大鼠体质量、摄食量及棕色脂肪组织(brown adipose tissue,BAT)温度变化;采用Western blot与免疫荧光技术检测下丘脑内质网应激标志物(pPERK)、促炎因子(IL-1β)及摄食抑制肽阿黑皮素原(proopiomelan ocortin,POMC)蛋白表达;运用Western blot、免疫组化等方法分析BAT中产热因子(UCP-1、PGC1α)、pPERK、NLRP3炎症小体和IL-1β的蛋白表达,并结合HE染色观察BAT形态学改变。结果:与空白对照组相比,利培酮组大鼠摄食量增加(P<0.05)、BAT温度降低(P<0.05)、累积体质量增加49%;4-PBA干预后,大鼠摄食量减少(P<0.05)、BAT温度显著回升(P<0.05),累积体质量增幅降低27%。机制研究表明,在下丘脑中,4-PBA显著逆转利培酮诱导的pPERK、IL-1β表达上调(均为P<0.05),并增加POMC蛋白表达(P<0.05);在BAT中,4-PBA显著上调产热因子UCP-1和PGC1α的蛋白表达,下调pPERK、NLRP3和IL-1β的蛋白表达(均为P<0.05),并有效减轻利培酮诱导的棕色脂肪白化现象。结论:4-PBA可通过双重调控下丘脑摄食和BAT产热功能,抑制内质网应激-炎症级联反应,上调POMC表达,从而改善利培酮诱导的肥胖,为药源性肥胖的临床干预提供了潜在治疗靶点。 展开更多
关键词 4-苯基丁酸 利培酮 药源性肥胖 内质网应激 棕色脂肪组织产热
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A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers 被引量:2
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作者 HU Wei Qiong ZHOU Wei Guang +8 位作者 ZHOU Guang Wei LIAO Jia Xi SHI Jia Xing XIE FengYang LI Shou Heng WANG Yong FENG Xian Hong GU Xiu Li CHEN Bi Feng 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2024年第5期445-456,共12页
Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of dig... Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population. 展开更多
关键词 LEPR gene rs1137101 Digestive system cancers Genetic susceptibility META-ANALYSIS
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高分子表(界)面吸附中的单分子动态学图景教学
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作者 程冬炳 沈雷 《高分子通报》 CAS CSCD 北大核心 2024年第6期846-850,共5页
“高分子表(界)面吸附”是《高分子物理》中聚合物表面与界面章节的重要组成部分,其研究关乎高分子复合材料制备、胶体稳定、废水处理、生命体系等诸多涉及大分子在表(界)面上吸附的领域,具有重要理论与实际意义。为提高本科生对高分子... “高分子表(界)面吸附”是《高分子物理》中聚合物表面与界面章节的重要组成部分,其研究关乎高分子复合材料制备、胶体稳定、废水处理、生命体系等诸多涉及大分子在表(界)面上吸附的领域,具有重要理论与实际意义。为提高本科生对高分子表(界)面吸附现象的认知,本文提出从单分子层面入手,通过展示科研中观察到的高分子单链在表(界)面上的二维扩散运动图景,引入生动实例,阐述其“吸附-扩散-脱附”动态学模型,帮助学生厘清“高分子表(界)面吸附”过程的微观分子机制,突出传统教学中缺乏的动态学思维,培养学生正确的世界观和方法论,这对学生运用正确的高分子物理学科思维解决高分子相关实际问题十分必要。 展开更多
关键词 高分子表(界)面吸附 动态学 单分子示踪
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The rs2227481 C>T Polymorphism in the IL22 Gene Promoter Significantly Reduces the Risk of Liver,Lung,and Gastric Cancer in a Han Chinese Population 被引量:1
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作者 CHAI Long Long XIAO Ying Xuan +6 位作者 MENG Ling Han WANG Huan FENG Xian Hong GU Xiu Li LI Qi Chang XIONG Qian Tao CHEN Bi Feng 《Biomedical and Environmental Sciences》 CSCD 2021年第7期572-576,共5页
Cancer is a serious threat to public health and the economy worldwide.Statistical data from the World Health Organization(WHO)in 2018 have demonstrated that lung cancer is the most commonly diagnosed cancer(11.6%of th... Cancer is a serious threat to public health and the economy worldwide.Statistical data from the World Health Organization(WHO)in 2018 have demonstrated that lung cancer is the most commonly diagnosed cancer(11.6%of the total cases)and the leading cause of cancer death(18.4%of the total cancer deaths),closely followed bygastric cancer(5.7%and 8.2%),and liver cancer(4.7%and 8.2%). 展开更多
关键词 IL22 Cancer GASTRIC
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The ribonuclease E regulator RebA is essential for diazotrophic growth in the cyanobacterium Anabaena PCC 7120
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作者 Sujuan Liu Zhenyu Wang +4 位作者 Guiming Lin Wenkai Li Xiaoli Zeng Ju-Yuan Zhang Cheng-Cai Zhang 《mLife》 2025年第5期516-526,共11页
Ribonuclease E(RNase E)is central to bacterial RNA metabolism.In cyanobacteria,its activity is inhibited by RebA,a key mechanism for controlling cell morphology.Here,we demonstrate that rebA is essential for diazotrop... Ribonuclease E(RNase E)is central to bacterial RNA metabolism.In cyanobacteria,its activity is inhibited by RebA,a key mechanism for controlling cell morphology.Here,we demonstrate that rebA is essential for diazotrophic growth of Anabaena PCC 7120,a filamentous cyanobacterium capable of forming heterocysts-specialized nitrogen-fixing cells-upon nitrogen starvation.The rebA mutant strain(ΔrebA)showed severe growth defects in nitrogen-deprived conditions,despite forming more heterocysts than the wild type.With a GFP fusion strain,we show that RebA is transiently upregulated during heterocyst differentiation.Microscopic and ultrastructural analyses revealed thatΔrebA heterocysts accumulated abnormally large cyanophycin granules,while vegetative cells showed reduced pigment levels and disorganized thylakoid membranes,phenotypes indicative of a severe nitrogen deficiency response.However,esculin tracer diffusion and SepJ-GFP localization inΔrebA were comparable to the wild type,suggesting that cell-cell communication via septal junctions remains functional.Thus,the growth defect likely results from impaired degradation or mobilization of fixed nitrogen.Notably,theΔrebA phenotype could be rescued only by wild-type RebA,but not by variants unable to bind RNase E,indicating that RebA's function depends on its modulation of RNase E activity.Together,these findings reveal a key posttranscriptional mechanism linking RNase E regulation to heterocyst development and intercellular nutrient transfer,highlighting the importance of regulated RNA metabolism for diazotrophic growth. 展开更多
关键词 CYANOBACTERIA diazotrophic growth HETEROCYST ribonuclease E RNA metabolism
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“Life is short,and art is long”:RNA degradation in cyanobacteria and model bacteria 被引量:1
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作者 Ju-Yuan Zhang Wolfgang R.Hess Cheng-Cai Zhang 《mLife》 2022年第1期21-39,共19页
RNA turnover plays critical roles in the regulation of gene expression and allows cells to respond rapidly to environmental changes.In bacteria,the mechanisms of RNA turnover have been extensively studied in the model... RNA turnover plays critical roles in the regulation of gene expression and allows cells to respond rapidly to environmental changes.In bacteria,the mechanisms of RNA turnover have been extensively studied in the models Escherichia coli and Bacillus subtilis,but not much is known in other bacteria.Cyanobacteria are a diverse group of photosynthetic organisms that have great potential for the sustainable production of valuable products using CO_(2)and solar energy.A better understanding of the regulation of RNA decay is important for both basic and applied studies of cyanobacteria.Genomic analysis shows that cyanobacteria have more than 10 ribonucleases and related proteins in common with E.coli and B.subtilis,and only a limited number of them have been experimentally investigated.In this review,we summarize the current knowledge about these RNAturnover-related proteins in cyanobacteria.Although many of them are biochemically similar to their counterparts in E.coli and B.subtilis,they appear to have distinct cellular functions,suggesting a different mechanism of RNA turnover regulation in cyanobacteria.The identification of new players involved in the regulation of RNA turnover and the elucidation of their biological functions are among the future challenges in this field. 展开更多
关键词 CYANOBACTERIA RNA maturation RNA metabolism RNA turnover RIBONUCLEASES
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Metabolic activities of marine ammonia-oxidizing archaea orchestrated by quorum sensing
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作者 Olivier Pereira Wei Qin +6 位作者 Pierre E.Galand Didier Debroas Raphael Lami Corentin Hochart Yangkai Zhou Jin Zhou Chuanlun Zhang 《mLife》 CSCD 2024年第3期417-429,共13页
Ammonia-oxidizing archaea(AOA)play crucial roles in marine carbon and nitrogen cycles by fixing inorganic carbon and performing the initial step of nitrification.Evaluation of carbon and nitrogen metabolism popularly ... Ammonia-oxidizing archaea(AOA)play crucial roles in marine carbon and nitrogen cycles by fixing inorganic carbon and performing the initial step of nitrification.Evaluation of carbon and nitrogen metabolism popularly relies on functional genes such as amoA and accA.Increasing studies suggest that quorum sensing(QS)mainly studied in biofilms for bacteria may serve as a universal communication and regulatory mechanism among prokaryotes;however,this has yet to be demonstrated in marine planktonic archaea.To bridge this knowledge gap,we employed a combination of metabolic activity markers(amoA,accA,and grs)to elucidate the regulation of AOA-mediated nitrogen,carbon processes,and their interactions with the sur-rounding heterotrophic population.Through co-transcription investigations linking metabolic markers to potential key QS genes,we discovered that QS molecules could regulate AOA's carbon,nitrogen,and lipid metabolisms under different conditions.Interestingly,specific AOA ecotypes showed a preference for employing distinct QS systems and a distinct QS circuit involving a typical population.Overall,our data demonstrate that Qs orchestrates nitrogen and carbon metabolism,including the exchange of organic metabolites between AOA and surrounding heterotrophic bacteria,which has been pre-viously overlooked in marine AOA research. 展开更多
关键词 AOA functional genes marine ammonia-oxidizing archaea NETWORKING quorum sensing Tara Oceans
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