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| 1 | 胆汁酸的合成调控及其在生理与病理中的功能机制显示文摘胆汁酸是一类胆固醇的代谢物,在机体胆固醇与能量代谢平衡和小肠营养物质吸收等方面起着重要作用。肝脏是合成胆汁酸的主要场所。饥饿条件下,胆汁酸从肝脏分泌进入胆管并被储存到胆囊;进食后胆囊收缩,贮存的胆汁酸被排出进入小肠。在小肠中,95%的胆汁酸会被小肠重新吸收,通过肝门静脉返回肝脏,这一过程被称为胆汁酸的肝肠循环。胆汁酸一方面作为乳化剂促进小肠中脂类等物质的吸收及转运,同时也作为重要的信号分子与多种受体结合,包括核受体法呢醇X受体(farnesoidXreceptor,FXR)、维生素D受体(vitaminD receptor,VDR)、孕烷X受体(pregnaneXreceptor,PXR)以及细胞膜表面受体G蛋白偶联受体(cellmembrane surface receptor-G protein coupled receptor, TGR5)等,在调节体内胆汁酸的代谢平衡、糖脂代谢与能量代谢平衡等方面发挥重要作用。肝细胞生长因子(hepatocyte growth factor, HGF)、白介素1-(interleukin-1, IL-1)及肿瘤坏死因子(tumor necrosis factor, TNF-)等协同作用构成了胆汁酸合成的精密调控网络。本文主要综述了胆汁酸的合成调控及其功能方面的最新研究进展,旨在为胆汁酸代谢相关研究提供参考。 | 刘笑 王琰 | 2019 | 遗传2019，41，5： | 22 |
| 2 | 基于斑马鱼模型与中医药整合药理学平台研究天麻的抗癫痫作用及潜在机制显示文摘目的利用斑马鱼模型和中医药整合药理学平台(TCMIP),探究天麻抗癫痫的主要活性成分及潜在的作用机制。方法采用健康发育至72h的AB系斑马鱼幼鱼为实验动物,以氨茶碱诱导形成癫痫模型,观察天麻对斑马鱼癫痫样行为的改善作用;利用TCMIP筛选天麻抗癫痫的靶点,构建天麻与癫痫的蛋白质相互作用(protein-protein interaction,PPI)网络,绘制药材-成分-靶点-通路-疾病网络;利用Autodock vina软件对活性成分和靶点进行分子对接。结果天麻对氨茶碱诱导的斑马鱼的癫痫样行为发生频率具有显著改善作用(P<0.05)。通过TCMIPv2.0整合分析发现,天麻抗癫痫的核心靶点有25个,天麻素、天麻醚苷、谷甾醇、棕榈酸、西托糖苷可能是天麻抗癫痫的主要活性成分;这些活性成分可以直接作用于相应关键靶点,参与调节神经递质的平衡、维持神经元细胞正常电生理活动并影响酮体生成。结论天麻对癫痫样症状具有明显的改善作用,其抗癫痫的潜在机制可能与调节神经递质的平衡、神经元细胞的电生理稳态和酮体的生成有关,为天麻的临床应用提供理论依据。 | 裴文强 单毅 张友刚 贾献慧 汪海洋 王晓静 田青平 韩利文 姚庆强 | 2021 | 中草药2021，52，7： | 16 |
| 3 | 胆汁类动物药中胆汁酸化学成分和药理作用研究进展显示文摘动物胆汁作为药物应用防治疾病有着悠久的历史,主要包括鸡、猪、蛇、牛、熊等的胆汁,而胆汁酸类成分是胆汁的重要活性成分。研究表明,胆汁酸类成分主要包括胆酸、去氧胆酸、鹅去氧胆酸、熊去氧胆酸、牛磺鹅去氧胆酸等,能通过肝肠循环与肠道微生物互相影响,在营养吸收和分配、代谢调节和动态平衡方面起着重要的作用。胆汁中胆汁酸类成分具有保肝、利胆、溶胆结石、抗癌、保护肾脏、保护心脑组织、保护神经、镇咳、平喘、祛痰、治疗眼病、调节肠道功能、调节血糖等药理作用,在临床上应用广泛。为了更好地发挥胆汁酸的药用价值以及在产品开发中的应用,该文通过对药用动物胆汁中胆汁酸类化学成分和药理作用研究进展进行归纳、总结与分析,以期为胆汁酸的进一步开发利用提供科学依据和参考。 | 陈星玲 宿树兰 刘睿 钱大玮 陈丽玲 邱丽萍 段金廒 | 2021 | 中国中药杂志2021，46，19： | 12 |
| 4 | Dephosphorylation of cGAS by PPP6C impairs its substrate binding activity and innate antiviral response显示文摘The cyclic GMP-AMP (cGAMP) synthase (cGAS) plays a critical role in host defense by sensing cytosollc DNA derived from microbial pathogens or mls-located cellular DNA.Upon DNA binding,cGAS utilizes GTP and ATP as substrates to synthesize cGAMP,leading to MITA-mediated innate immune response.In this study,we identified the phosphatase PPP6C as a negative regulator of cGASmediated innate immune response.PPP6C is constitutively associated with cGAS in un-stimulated cells.DNA virus infection causes rapid disassociation of PPP6C from cGAS,resulting in phosphorylation of human cGAS S435 or mouse cGAS S420 in its catalytic pocket.Mutation of this eerine residue of cGAS impairs its ability to synthesize cGAMP upon DNA virus infection.In vitro experiments indicate that S420-phosphorylated mcGAS has higher affinity to GTP and enzymatic activity.PPP6Cdeficiency promotes innate immune response to DNA virus in various cells.Our findings suggest that PPP6Cmediated dephosphorylation of a catalytic pocket serine residue of cGAS impairs its substrate binding activity and innate immune response,which provides a mechanism for keeping the DNA sensor cGAS inactive in the absence of infection to avoid autoimmune response. | Mi Li Hong-Bing Shu | 2020 | Protein & Cell2020，11，8： | 7 |
| 5 | 刘启泉从胆论治腹泻型肠易激综合征显示文摘腹泻型肠易激综合征(diarrhea-predominant irrita blebowel syndrome, IBS-D)发病的本质是气血运行失调,情志饮食刺激是重要诱因。气机病变取决于胆,胆作为枢纽,通过调节气机升降影响周身气血的运行,影响情志和消化。IBS-D气机郁滞明显,腹痛较为严重,有泻后痛减特点者,常伴有脾虚的表现,重在疏肝利胆,理气止泻。IBS-D湿热明显者,为气滞津停,水液运行不畅,聚而生湿,日久郁而生热,凝炼成痰,痰留脾胃,则食少纳呆、脘闷不舒,临证应清胆化痰,除湿止泻。IBS-D伴有上消化道症状者,当注意调和胆胃,止痛止泻。IBS-D患者常合并焦虑抑郁等神志异常的表现,是因心胆气虚,胆失决断,神不内守,故应补胆安神,温肾止泻。 | 王俞铧 王雨鸽 许静茹 赵倩文 孙建慧 韩增银 王盼 刘文静 刘启泉 | 2022 | 中医学报2022，37，3： | 6 |
| 6 | 基于网络药理学牛磺石胆酸抗炎作用及机制显示文摘目的通过网络药理学分析牛磺石胆酸(taurolithocholic acid,TLCA)抗炎作用机制。方法从数据库中获取TLCA的靶标,构建TLCA抗炎作用的PPI网络并进行可视化。通过GO和KEGG分析作用靶点的基因功能及信号通路。选择靶标TGR5与TLCA进行分子对接评价结合性。用LPS和IFN-γ诱导的RAW264.7细胞验证TLCA抗炎作用。结果筛选出87个潜在抗炎靶点。GO分析表明这些基因主要富集于炎症反应调控、膜筏和蛋白酪氨酸激酶等方面。KEGG通路分析结果提示,PI3K-Akt信号通路、人巨细胞病毒感染可能是TLCA抗炎症的关键通路。细胞实验结果表明,TLCA可降低LPS和IFN-γ诱导的RAW264.7细胞的炎症反应,该作用与TLCA经TGR5下调NF-κB信号通路有关。结论网络药理学揭示了TLCA抗炎的潜在靶点;细胞实验结果表明TLCA可能通过膜受体TGR5调节关键的炎症信号通路。 | 王妙然 李月 张芸绮 蔺晓菁 钟莹 陈春秀 周永 肖晓秋 李继斌 | 2021 | 中国药理学通报2021，37，11： | 4 |
| 7 | VRK2 is involved in the innate antiviral response by promoting mitostress-induced mtDNA release显示文摘Mitochondrial stress (mitostress) triggered by viral infection or mitochondrial dysfunction causes the release of mitochondrial DNA (mtDNA) into the cytosol and activates the cGAS-mediated innate immune response. The regulation of mtDNA release upon mitostress remains uncharacterized. Here, we identified mitochondria-associated vaccinia virus-related kinase 2 (VRK2) as a key regulator of this process. VRK2 deficiency inhibited the induction of antiviral genes and caused earlier and higher mortality in mice after viral infection. Upon viral infection, VRK2 associated with voltage-dependent anion channel 1 (VDAC1) and promoted VDAC1 oligomerization and mtDNA release, leading to the cGAS-mediated innate immune response. VRK2 was also required for mtDNA release and cGAS-mediated innate immunity triggered by nonviral factors that cause Ca^(2+) overload but was not required for the cytosolic nucleic acid-triggered innate immune response. Thus, VRK2 plays a crucial role in the mtDNA-triggered innate immune response and may be a potential therapeutic target for infectious and autoimmune diseases associated with mtDNA release. | Wen-Rui He Li-Bo Cao Yu-Lin Yang Duo Hua Ming-Ming Hu Hong-Bing Shu | 2021 | Cellular & Molecular Immunology2021，18，5： | 3 |
| 8 | The interactions between cGAS-STING pathway and pathogens显示文摘Cytosolic DNA is an indicator of pathogen invasion or DNA damage.The cytosolic DNA sensor cyclic guanosine monophosphateadenosine monophosphate(cGAMP)synthase(cGAS)detects DNA and then mediates downstream immune responses through the molecule stimulator of interferon genes(STING,also known as MITA,MPYS,ERIS and TMEM173).Recent studies focusing on the roles of the cGAS-STING pathway in evolutionary distant species have partly sketched how the mammalian cGAS-STING pathways are shaped and have revealed its evolutionarily conserved mechanism in combating pathogens.Both this pathway and pathogens have developed sophisticated strategies to counteract each other for their survival.Here,we summarise current knowledge on the interactions between the cGAS-STING pathway and pathogens from both evolutionary and mechanistic perspectives.Deeper insight into these interactions might enable us to clarify the pathogenesis of certain infectious diseases and better harness the cGAS-STING pathway for antimicrobial methods. | Zhangliang Cheng Tong Dai Xuelin He Zhengkui Zhang Feng Xie Shuai Wang Long Zhang Fangfang Zhou | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 3 |
| 9 | 运动应激介导线粒体DAMP对先天性免疫的调控作用研究进展显示文摘线粒体是先天性免疫的关键调控者,具体表现为:线粒体可以通过释放多种线粒体损伤相关分子模式(damageassociated molecular patterns,DAMPs)来诱发先天性免疫应答,如线粒体DNA(mitochondrial DNA,mtDNA)、线粒体转录因子A(mitochondrial transcription factor A,TFAM)、线粒体N-甲酰肽(mitochondrial N-formyl peptides,F-MITs)、ATP等.然而,病毒也利用相应的机制抑制线粒体DAMPs诱导的先天性免疫.众所周知,适度的运动对机体免疫系统有着积极健康的影响,而大强度运动反之.再者,运动又与线粒体的关系密切.因此,运动很可能通过线粒体DAMPs的释放来调控先天性免疫.本文综述了线粒体DAMPs与先天性免疫的联系,并探讨了运动在其中所扮演的角色,以期从线粒体的视角为运动对先天性免疫的调控机制提供新的研究思路. | 戈哲 丁树哲 | 2021 | 生物化学与生物物理进展2021，48，12： | 2 |
| 10 | 血清总胆固醇水平对肝衰竭患者预后的影响显示文摘肝衰竭是临床常见的严重肝病症候群,病死率极高,目前并无治愈方法。因此研究与肝衰竭患者预后相关因素十分必要。胆固醇(TC)不仅是一个结构成分,而且作为一个相关的脂质参与了多种类型的肝细胞中间代谢,是维生素D、胆汁酸及类固醇激素等的合成原料[1,2]。肝衰竭患者肝脏受损严重,其合成、排泄、解毒和生物转化等功能出现严重障碍,观察其相关临床指标的变化对判断疾病进展及患者预后具有重要意义。近年来,国内外已有许多关于TC水平与肝病患者预后相关性的研究报道[3],我们以“肝衰竭血清总TC”为检索关键词在CKNI及万方等数据库搜集近5年内相关文献,分析两者关系,现综述如下。 | 杨诚 杨华升 胡建华 徐琛 | 2021 | 中西医结合肝病杂志2021，31，11： | 2 |
| 11 | 胆汁酸生物学功能及其在水产养殖中的应用前景显示文摘胆汁酸是胆汁的重要活性成分,主要包括胆酸、去氧胆酸、牛黄鹅去氧胆酸、鹅去氧胆酸、熊去氧胆酸等多种成分,在动物脂肪代谢过程中发挥重要作用,具有抗炎、促进消化吸收、提高免疫力、保障肠道功能等多种生物学功能。胆汁酸作为一种新型的饲料添加剂,在水产养殖中发挥重要功效和作用。文章总结胆汁酸的生物学功能,综述胆汁酸在水产养殖生产中的应用,以期为胆汁酸进一步的开发与利用提供参考。 | 许长峰 王海丽 | 2023 | 饲料研究2023，46，4： | 1 |
| 12 | Taurocholic acid inhibits the response to interferon-αtherapy in patients with HBeAg-positive chronic hepatitis B by impairing CD8^(+)T and NK cell function显示文摘Pegylated interferon-alpha (PegIFNα) therapy has limited effectiveness in hepatitis B e-antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. However, the mechanism underlying this failure is poorly understood. We aimed to investigate the influence of bile acids (BAs), especially taurocholic acid (TCA), on the response to PegIFNα therapy in CHB patients. Here, we used mass spectrometry to determine serum BA profiles in 110 patients with chronic HBV infection and 20 healthy controls (HCs). We found that serum BAs, especially TCA, were significantly elevated in HBeAg-positive CHB patients compared with those in HCs and patients in other phases of chronic HBV infection. Moreover, serum BAs, particularly TCA, inhibited the response to PegIFNα therapy in HBeAg-positive CHB patients. Mechanistically, the expression levels of IFN-γ, TNF-α, granzyme B, and perforin were measured using flow cytometry to assess the effector functions of immune cells in patients with low or high BA levels. We found that BAs reduced the number and proportion and impaired the effector functions of CD3^(+)CD8^(+) T cells and natural killer (NK) cells in HBeAg-positive CHB patients. TCA in particular reduced the frequency and impaired the effector functions of CD3^(+)CD8^(+) T and NK cells in vitro and in vivo and inhibited the immunoregulatory activity of IFN-α in vitro. Thus, our results show that BAs, especially TCA, inhibit the response to PegIFNα therapy by impairing the effector functions of CD3^(+)CD8^(+) T and NK cells in HBeAg-positive CHB patients. Our findings suggest that targeting TCA could be a promising approach for restoring IFN-α responsiveness during CHB treatment. | Zhen Xun Jinpiao Lin Qingqing Yu Can Liu Jinlan Huang Hongyan Shang Jianhui Guo Yuchen Ye Wennan Wu Yongbin Zeng Songhang Wu Siyi Xu Tianbin Chen Jing Chen Qishui Ou | 2021 | Cellular & Molecular Immunology2021，18，2： | 1 |
| 13 | Mitochondrial DNA-triggered innate immune response:mechanisms and diseases显示文摘Various cellular stress conditions trigger mitochondrial DNA(mtDNA)release from mitochondria into the cytosol.The released mtDNA is sensed by the cGAS-MITA/STING pathway,resulting in the induced expression of type I interferon and other effector genes.These processes contribute to the innate immune response to viral infection and other stress factors.The deregulation of these processes causes autoimmune diseases,inflammatory metabolic disorders and cancer.Therefore,the cGAS-MITA/STING pathway is a potential target for intervention in infectious,inflammatory and autoimmune diseases as well as cancer.In this review,we focus on the mechanisms underlying the mtDNA-triggered activation of the cGAS-MITA/STING pathway,the effects of the pathway under various physiological and pathological conditions,and advances in the development of drugs that target cGAS and MITA/STING. | Ming-Ming Hu Hong-Bing Shu | 2023 | Cellular & Molecular Immunology2023，20，12： | 0 |
| 14 | Mitotic inactivation of the cGAS-MITA/STING pathways显示文摘The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-mediator of interferon response factor 3 acti-vation/stimulator of interferon genes(MITA/STING)axis has emerged as a major pathway,which senses microbial or mislocated cellular DNA in the cytosol to trigger innate immune responses.cGAS senses cytosolic DNA without a preference of self-or nonself-DNA.How the cGAS-MITA/STING axis is inactivated upon nuclear envelope breakdown(NEBD)at mitotic entry in vertebrate cells to avoid self-DNA sensing remains unclear until very recently.In this review,we summarize the recent advances on how cGAS responds to chromosomes upon NEBD and the mechanisms involved in the inactivation of the cGAS-MITA/STING pathways in mitosis. | Li Zhong Hong-Bing Shu | 2021 | Journal of Molecular Cell Biology2021，13，10： | 0 |
| 15 | 肠道菌群调控干扰素应答在病毒与肿瘤性疾病中的研究进展显示文摘由诱生和效应2个阶段构成的干扰素应答是抗病毒与肿瘤免疫的经典生物学事件,但干扰素拮抗与药物毒性限制了干扰素的临床应用。新近大量实验证据揭示了肠道菌群及其代谢产物与干扰素应答网络在病毒与肿瘤性疾病中的关键作用,为精准修正肠道菌群实现抗病毒或肿瘤治疗带来新的思路。现就肠道菌群调控干扰素应答在病毒与肿瘤性疾病中的作用进行概述,以期为进一步基础和临床转化研究提供参考依据。 | 陈邦涛 陈诚 毕杨辉 何松 郝飞 | 2023 | 中华传染病杂志2023，41，5： | 0 |
| 16 | 乳杆菌bsh基因的高效表达及高活性酶蛋白获得显示文摘目的探讨乳杆菌bsh基因的高效表达及胆盐水解酶(BSH)的高活性酶蛋白获得。方法从本实验室保存的12株乳杆菌菌株中,通过Ca2+沉淀法初筛获得具BSH活性的菌株,根据GenBank上公布的16S rRNA同源性最高的乳杆菌的BSH全基因序列,设计特异性引物,PCR扩增获得bsh基因并克隆至表达载体pET-28α,构建BL21-pET-28α-bsh原核表达体系。经IPTG诱导后,对表达产物进行SDS-PAGE分析及Western blot验证。结果研究表明在分子质量大小约35、37 kD处有预期条带出现,初步表明BSH蛋白表达成功。进而对表达各条件进行优化,最佳酶活条件为IPTG浓度0.1 mmol/L、诱导pH 6.5、诱导温度37℃、诱导时间1 h。经镍柱亲和层析纯化制备BSH制剂,邻苯三酚红钼法蛋白浓度测定为1446 mg/dL,茚三酮法测酶活性最高可达21248.27 U/(g·prot),为纯化前的635.4倍。结论乳杆菌bsh基因可溶性表达成功且高酶活BSH纯化获取为进一步的研究和药物转化奠定基础。 | 范逸雯 宣雷杰 龚昊辰 陈星宇 施涛 黄泽宇 武佳 曾爱兵 | 2020 | 中国微生态学杂志2020，32，11： | 0 |
| 17 | 核酸免疫识别的机制和功能及酪氨酸磷酸化修饰调控显示文摘核酸天然免疫识别是一种普遍存在且高度保守的免疫应答机制,负责监测和响应病原体入侵或组织损伤,进而在宿主防御、自身免疫反应、细胞命运决定以及肿瘤发生发展中发挥关键作用。酪氨酸磷酸化作为一类主要的蛋白质翻译后修饰机制,在核酸识别通路中发挥重要调控功能。其中,介导核酸免疫识别通路的核心成员环鸟苷酸-腺苷酸合成酶(cGAS)、干扰素基因刺激因子(STING)以及TANK结合激酶1(TBK1)等蛋白均受到酪氨酸磷酸化修饰引发的活性调控,进而影响生理或病理条件下宿主的抗病毒防御和抗肿瘤免疫能力。本文综述了酪氨酸激酶和酪氨酸磷酸化修饰在核酸免疫识别中的调控作用及研究现状,讨论了靶向酪氨酸磷酸化在抗肿瘤免疫中的功能和潜在应用,以期为理解并拓展全新的抗肿瘤手段提供思路。 | 刘盛铎 徐平龙 | 2024 | 浙江大学学报(医学版)2024，53，1： | 0 |
| 18 | 从“胆”认识肠易激综合征的发病机制显示文摘中医学既往多从肝脾论治肠易激综合征,以疏肝健脾为基本治法。基于对中西医理论的分析及临床观察,认为胆腑参与消化和精神活动,与肠易激综合征的相关性更强。中医胆腑的生理功能异常时,其藏精汁助运化、主决断调情志、主升发调气机和司勇怯御外辱的功能失常,会出现肠道菌群失调、内脏高敏感、焦虑抑郁状态、胃肠道功能紊乱和肠道感染,均与现代医学对肠易激综合征发病机制的认识相合,故而提出从“胆”认识本病的发病,为本病的防治提供新思路。 | 刘镇亚 王晓鸽 李合国 郭敏 杨竹青 王璐 姚翠翠 | 2023 | 中医杂志2023，64，5： | 0 |
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