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Differentiation and immunosuppressive function of CD19^(+)CD24^(hi)CD27^(+) regulatory B cells are regulated through the miR-29a-3p/NFAT5 pathway
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作者 Jin-Yang Li Tian-Shuo Feng +5 位作者 Ji Gao Xin-Xiang Yang Xiang-Cheng Li Zhen-Hua Deng Yong-Xiang Xia Zheng-Shan Wu 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2024年第5期472-480,共9页
Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the targe... Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation. 展开更多
关键词 regulatory B cells miR-29a-3p NFAT5 Liver transplantation
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拮抗CC趋化因子受体5信号诱导肿瘤细胞凋亡并调节肿瘤微环境抑制肿瘤生长
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作者 何伟 刘丽萍 +3 位作者 卓静薇 张小冬 杨通 冯巨滨 《实用医学杂志》 CAS 北大核心 2024年第9期1204-1210,共7页
目的探索拮抗CC趋化因子受体5(CCR5)信号通路对肿瘤生长和肿瘤微环境的影响。方法采用CCK8细胞毒试验研究CCR5选择性拮抗剂Maraviroc体外对小鼠Lewis肺腺癌细胞增殖的影响,并运用流式细胞术和RT-PCR检测肿瘤细胞凋亡和Caspase 8基因的... 目的探索拮抗CC趋化因子受体5(CCR5)信号通路对肿瘤生长和肿瘤微环境的影响。方法采用CCK8细胞毒试验研究CCR5选择性拮抗剂Maraviroc体外对小鼠Lewis肺腺癌细胞增殖的影响,并运用流式细胞术和RT-PCR检测肿瘤细胞凋亡和Caspase 8基因的表达。然后采用免疫荧光组织化学染色法研究了Maraviroc对小鼠体内肿瘤生长和肿瘤微环境中CD4^(+)和CD8^(+)以及Foxp3^(+)细胞比例的影响。结果拮抗CCR5信号在体内外均能够抑制癌细胞的生长。体外研究发现:CCR5拮抗剂可通过增强凋亡基因Caspase 8表达而诱导肿瘤细胞凋亡。在小鼠体内,CCR5拮抗剂可明显增加肿瘤微环境中CD4^(+)和CD8^(+)细胞的浸润而减少Foxp3^(+)细胞的浸润。结论拮抗CCR5信号可能通过诱导肿瘤细胞凋亡,逆转免疫抑制性肿瘤微环境而抑制肿瘤生长。 展开更多
关键词 CC趋化因子受体5 肿瘤微环境 凋亡 调节性T细胞
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MS19通过抑制IRF5表达调控巨噬细胞极化减轻CTD-ILD肺部炎症的作用研究
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作者 陈珊珊 明倩文 +1 位作者 肖恩华 王晓红 《中南药学》 CAS 2024年第5期1178-1185,共8页
目的 探讨MS19通过靶向干扰素调节因子5(IRF5)对结缔组织疾病相关肺间质病变(CTD-ILD)小鼠模型肺部炎症的治疗作用及其相关机制。方法 动物实验:构建CTD-ILD小鼠模型,予以MS19干预,研究MS19对CTD-ILD小鼠肺部炎症的影响。细胞实验:对RAW... 目的 探讨MS19通过靶向干扰素调节因子5(IRF5)对结缔组织疾病相关肺间质病变(CTD-ILD)小鼠模型肺部炎症的治疗作用及其相关机制。方法 动物实验:构建CTD-ILD小鼠模型,予以MS19干预,研究MS19对CTD-ILD小鼠肺部炎症的影响。细胞实验:对RAW264.7细胞进行OE-IRF5转染,然后予以MS19干预,研究MS19对IRF5调控的巨噬细胞M1型极化及炎症反应的影响。结果 动物实验:CTD-ILD小鼠出现明显的肺部炎症,小鼠支气管肺泡灌洗液(BALF)中IRF5的表达增高、巨噬细胞M1型极化增加及促炎因子(TNF-α、IL-6和IL-1β)的表达升高;而MS19干预后,CTD-ILD小鼠的肺部炎症减轻,BALF中IRF5表达降低、巨噬细胞M1型极化减少及促炎因子表达下降。细胞实验:脂多糖诱导巨噬细胞M1型极化、促炎因子表达增加;转染OE-IRF5后,巨噬细胞M1型极化增加、促炎因子表达增加;MS19干预后,巨噬细胞M1型极化减少、促炎因子表达减少。结论 MS19通过靶向抑制IRF5调控巨噬细胞极化及炎症反应,从而改善CTD-ILD的肺部炎症,为防治CTD-ILD提供潜在靶点和候选药物。 展开更多
关键词 MS19 寡聚脱氧核糖核苷酸 干扰素调节因子5 巨噬细胞极化 结缔组织疾病相关肺间质病变
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m5C甲基化修饰及其在肿瘤免疫治疗中的研究进展
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作者 陆云洋 杜维东 余东升 《口腔疾病防治》 2024年第2期143-148,共6页
表观遗传修饰在真核细胞生物学过程中有重要的调节作用。肿瘤免疫疗法是治疗癌症的重要手段和临床策略。5⁃甲基胞嘧啶(5⁃methylcytosine,m5C)是继N6甲基腺苷(N6⁃methyladenosine,m6A)之后发现的表观遗传调控网络的重要组成部分。RNA的m5... 表观遗传修饰在真核细胞生物学过程中有重要的调节作用。肿瘤免疫疗法是治疗癌症的重要手段和临床策略。5⁃甲基胞嘧啶(5⁃methylcytosine,m5C)是继N6甲基腺苷(N6⁃methyladenosine,m6A)之后发现的表观遗传调控网络的重要组成部分。RNA的m5C甲基化修饰能影响被修饰RNA分子的命运,并在包括RNA稳定性、蛋白质合成和转录调控在内的各种生物学过程中发挥重要作用。最近研究表明,m5C甲基转移酶、去甲基化酶、甲基化识别蛋白与多种细胞生物学过程和系统性疾病有关,包括肿瘤的发生、转移和肿瘤免疫微环境等。m5C甲基化修饰可在多个水平上广泛影响基因表达和肿瘤发生发展的生物学过程,但其具体机制及与其他表观遗传修饰的相互作用尚未阐明,其在恶性肿瘤中的调控机制、风险评估和靶向治疗的研究有待深入。本文将从m5C的动态调节网络、m5C修饰在实体瘤中的生物学作用及在肿瘤免疫治疗中的潜在靶点等进行综述。 展开更多
关键词 肿瘤 表观遗传修饰 甲基化修饰 5⁃甲基胞嘧啶 N6甲基腺苷 RNA甲基化 免疫治疗 肿瘤微环境 m5C调节蛋白
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Association Analysis between a Polymorphism in the 5' Regulatory Region of the IL-6 Gene and Litter Size in Pigs
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作者 Lu Yang Jinluan Fu Yanfeng Fu Aiguo Wang 《Journal of Animal Science and Biotechnology》 SCIE CAS 2011年第4期187-191,共5页
The aim of this study was to determine the effects of an IL-6 gene polymorphism, discovered in the 5' regulatory region, on porcine litter size. An association analysis was performed between the polymorphism and tota... The aim of this study was to determine the effects of an IL-6 gene polymorphism, discovered in the 5' regulatory region, on porcine litter size. An association analysis was performed between the polymorphism and total number born (TNB) and number born alive (NBA) in 421 sows. The polymorphism was at Hpy188I within the 5' regulatory region of IL- 6 gene. Three genotypes of AA, AG, and GG were detected in Landrace, and two genotypes, AA and AG, were detected in Yorkshire and Duroc pigs. The A allele was the superior allele in all three breeds, with allele frequencies ranging from 0. 901 to 0.993. The IL-6 genotype was highly significantly associated with TNB and NBA in the third and following parities ( P 〈 0.01 ), and with total parities ( P 〈 0.05). In general, the TNB and NBA showed a tendency of GG 〉 AG 〉 AA, indicating that the common allele was the least favorable for litter size. Thus, there is an enormous opportunity to increase litter size if this effect is confirmed in other studies. 展开更多
关键词 5 regulatory region IL-6 litter size PCR-RFLP PIG POLYMORPHISM
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辣木籽水提物对5-氟尿嘧啶诱导小鼠空肠黏膜炎的调节作用
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作者 赵润萍 黄开兰 +1 位作者 宋爽 白忠彬 《云南农业大学学报(自然科学版)》 CAS CSCD 北大核心 2024年第2期43-52,共10页
【目的】探究辣木籽水提物对5-氟尿嘧啶(5-fluorouracil,5-FU)诱导引起的小鼠空肠黏膜炎的改善作用。【方法】将50只SPF级雄性昆明小鼠随机分为正常组、模型组(腹腔注射5-FU 130 mg/kg)及辣木籽水提物低、中、高剂量组(分别灌胃辣木籽... 【目的】探究辣木籽水提物对5-氟尿嘧啶(5-fluorouracil,5-FU)诱导引起的小鼠空肠黏膜炎的改善作用。【方法】将50只SPF级雄性昆明小鼠随机分为正常组、模型组(腹腔注射5-FU 130 mg/kg)及辣木籽水提物低、中、高剂量组(分别灌胃辣木籽水提物50、100和200 mg/kg)。第1~14天,每日正常组和模型组灌胃蒸馏水,辣木籽组灌胃不同剂量的辣木籽水提物;第15~16天,每日正常组腹腔注射生理盐水,其余组均腹腔注射5-FU;第17~18天观察;第19天处死小鼠。每日记录小鼠摄食量、饮水量及体质量;采用HE染色并观察小鼠空肠组织形态学变化;采用免疫组化法检测空肠增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达情况;采用Tunel法检测空肠细胞的凋亡情况;采用酶联免疫法(ELISA)测定空肠组织IL-6、IL-1β和TNF-α炎症因子的含量变化。【结果】与模型组相比,辣木籽水提物高剂量组(200 mg/kg)可显著缓解小鼠体质量下降,极显著提高空肠绒毛高度、降低隐窝深度、增加绒毛高度与隐窝深度的比值,提高空肠PCNA表达量,降低细胞凋亡程度,抑制IL-6、IL-1β和TNF-α的表达。【结论】辣木籽水提物可改善5-FU诱导引起的小鼠空肠黏膜炎,且呈剂量依赖性。 展开更多
关键词 辣木籽水提物 5-氟尿嘧啶 空肠黏膜炎 调节作用
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干扰素调节因子5、粒细胞-巨噬细胞集落刺激因子在细菌性肺炎病儿血清中的表达及预后价值
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作者 唐才环 薛芳 +2 位作者 陈乙云 陈霞 黄惠敏 《安徽医药》 CAS 2024年第7期1425-1429,共5页
目的探讨干扰素调节因子5(interferon regulatory factor 5,IRF5)、粒细胞-巨噬细胞集落刺激因子(granulocyte-macro-phage colony-stimulating factor,GM-CSF)在细菌性肺炎病儿血清中的表达变化及疾病预后价值。方法选取2019年4月至202... 目的探讨干扰素调节因子5(interferon regulatory factor 5,IRF5)、粒细胞-巨噬细胞集落刺激因子(granulocyte-macro-phage colony-stimulating factor,GM-CSF)在细菌性肺炎病儿血清中的表达变化及疾病预后价值。方法选取2019年4月至2021年5月中国人民解放军联勤保障部队第九二八医院收治的细菌感染性肺炎病儿96例作为细菌组,同期非细菌感染性肺炎病儿88例作为非细菌组,另外选取健康体检儿童96例为对照组,收集检测三组病儿基本临床资料。检测血清中IRF5、GM-CSF及其组间差异;采用Pearson法分析细菌性肺炎病儿血清IRF5、GM-CSF水平与病情指标的相关性;应用受试者操作特征曲线(ROC曲线)分析IRF5、GM-CSF及二者联合预测细菌性肺炎预后的价值。结果细菌组血清IRF5水平[(38.85±13.86)ng/L]显著高于非细菌组[(11.15±4.37)ng/L]和对照组[(10.76±1.55)ng/L],且重症组高于轻症组(P<0.05);细菌组血清GM-CSF水平[(54.73±16.56)ng/L]显著低于非细菌组[(246.73±28.94)ng/L]和对照组[(250.64±55.67)ng/L],且重症组低于轻症组(P<0.05)。重症组气促、吐沫、三凹征、肺部明显湿啰音比例、C反应蛋白(C-reactive protein,CRP)、白细胞水平显著高于轻症组、非细菌组(P<0.05),轻症组、非细菌组CRP水平显著高于对照组(P<0.05),非细菌组CRP水平显著高于对照组(P<0.05)。血清IRF5水平与CRP、白细胞、临床肺部感染评分(clinical pulmonary infection score,CPIS)均呈正相关(r=0.34、0.36、0.41,P<0.05),血清GM-CSF水平与CRP、白细胞、CPIS均呈负相关(r=-0.40、-0.32、-0.45,P<0.05)。预后不良组血清IRF5水平高于预后良好组,血清GM-CSF水平低于预后良好组(P<0.05)。ROC曲线显示,IRF5、GM-CSF对预后预测的AUC分别为0.90、0.87,二者联合对预后预测的AUC为0.96,明显高于二者单独诊断,(Z联合vs.IRF5=2.86,P=0.004;Z联合vs.GM-CSF=2.24,P=0.025),其灵敏度、特异度分别为90.32%、90.77%。结论细菌性肺炎病儿血清IRF5水平升高,GM-CSF水平降低,二者在评估病情进展及疾病预后预测方面具有较高的价值。 展开更多
关键词 肺炎 细菌性 干扰素调节因子5 粒细胞-巨噬细胞集落刺激因子 表达变化 预后价值
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复发性口腔溃疡患儿血清IRF5、sTREM-1变化及对复发的预测价值
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作者 黄岩 王明丽 +1 位作者 边玉婷 刘元元 《国际检验医学杂志》 CAS 2024年第7期824-827,836,共5页
目的探讨复发性口腔溃疡患儿血清干扰素调节因子5(IRF5)、可溶性髓样细胞触发受体1(sTREM-1)水平变化及其对复发的预测价值。方法选取石家庄市妇幼保健院于2021年7月至2022年12月收治的146例复发性口腔溃疡患儿为观察组,并根据3个月内... 目的探讨复发性口腔溃疡患儿血清干扰素调节因子5(IRF5)、可溶性髓样细胞触发受体1(sTREM-1)水平变化及其对复发的预测价值。方法选取石家庄市妇幼保健院于2021年7月至2022年12月收治的146例复发性口腔溃疡患儿为观察组,并根据3个月内是否复发分为复发组(n=45)和未复发组(n=101)。另选取同期138例健康志愿者作为对照组。采用实时荧光定量PCR(qPCR)检测血清IRF5 mRNA表达水平,酶联免疫吸附试验(ELISA)检测血清sTREM-1、白细胞介素(IL)-6和IL-10表达水平,Pearson分析法分析复发性口腔溃疡患儿血清IRF5和sTREM-1水平与IL-6和IL-10水平的相关性,受试者工作特征(ROC)曲线分析血清IRF5和sTREM-1水平对复发性口腔溃疡患儿复发的预测价值。结果与对照组比较,观察组血清IRF5水平明显降低(P<0.05),sTREM-1、IL-6和IL-10水平明显升高(P<0.05);Pearson分析结果显示,复发性口腔溃疡患儿血清IRF5与IL-6、IL-10水平呈负相关(r=-0.531、-0.462,P<0.05),血清sTREM-1水平与IL-6、IL-10水平呈正相关(r=0.435、0.480,P<0.05);与未复发组比较,复发组患儿血清IRF5水平明显降低(P<0.05),sTREM-1水平明显升高(P<0.05)。ROC曲线分析结果显示,血清IRF5水平单独预测复发性口腔溃疡患儿复发的曲线下面积(AUC)为0.823,最佳cut-off值为0.85,灵敏度和特异度分别为75.56%、84.16%;血清sTREM-1水平单独预测复发性口腔溃疡患儿复发的AUC为0.833,灵敏度和特异度分别为68.89%、88.12%,最佳cut-off值为84.08 pg/mL;二者联合预测复发性口腔溃疡患儿复发的灵敏度和特异度分别为88.89%、82.18%,AUC为0.915,显著高于IRF5单独预测的AUC(Z=2.455,P=0.014)和sTREM-1单独预测的AUC(Z=2.790,P=0.005)。结论复发性口腔溃疡患儿血清IRF5水平较低、sTREM-1水平较高,二者联合对复发性口腔溃疡患儿再复发具有较高的预测价值。 展开更多
关键词 复发性口腔溃疡 干扰素调节因子5 可溶性髓样细胞触发受体1
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芪冬活血饮通过干扰素调节因子5抑制肺组织M1巨噬细胞募集治疗急性肺损伤的作用机制研究
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作者 王维斯 陈晔 +3 位作者 张丽婷 凌明珠 马兆娟 叶柏春 《浙江中西医结合杂志》 2024年第1期7-13,共7页
目的探讨芪冬活血饮通过干扰素调节因子5(IRF5)抑制肺组织M1巨噬细胞募集治疗急性肺损伤(ALI)的作用机制。方法24只C57BL/6小鼠随机分成四组,即空白组、模型组、芪冬活血饮低剂量(1 g/mL)和高剂量(2 g/mL)组,每组6只。采用脂多糖(LPS)制... 目的探讨芪冬活血饮通过干扰素调节因子5(IRF5)抑制肺组织M1巨噬细胞募集治疗急性肺损伤(ALI)的作用机制。方法24只C57BL/6小鼠随机分成四组,即空白组、模型组、芪冬活血饮低剂量(1 g/mL)和高剂量(2 g/mL)组,每组6只。采用脂多糖(LPS)制备ALI模型,采用苏木素-伊红(HE)染色法观察肺组织病理学改变;采用酶联免疫吸附试验(ELISA)检测肺泡灌洗液炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素(IL-6)]水平;采用原位末端转移酶标记技术(TUNEL)染色检测肺组织细胞凋亡情况;采用流式细胞术检测肺组织M1型巨噬细胞水平,采用蛋白质印迹法检测半胱氨酸天冬氨酸蛋白酶3剪切体(cleaved caspase3)、B淋巴细胞瘤-2蛋白(Bcl-2)、BCL2相关X蛋白(Bax)表达;采用实时荧光定量聚合酶链式反应(qRT-PCR)检测肺组织IRF5 mRNA表达;采用免疫荧光法检测IRF5蛋白在肺组织中的原位表达。结果与空白组比较,模型组小鼠肺组织肺泡结构破坏,肺间质水肿增厚,炎性细胞浸润,红细胞渗出,肺组织细胞凋亡显著增加,肺泡灌洗液炎症因子水平显著提高[IL-6:(964.87±85.12)pg/mL比(83.24±8.19)pg/mL,P<0.01;IL-1β:(127.64±10.98)pg/mL比(10.37±2.98)pg/mL,P<0.01;TNF-α:(148.74±13.98)pg/mL比(12.19±2.01)pg/mL,P<0.01],cleaved caspase3、Bax蛋白表达显著增加,Bcl-2蛋白水平降低;M1型巨噬细胞数量显著增加,肺组织IRF5 mRNA表达增加[(3.67±0.34)比(0.98±0.09),P<0.01],IRF5蛋白表达水平显著提高;与模型组比较,芪冬活血饮低、高剂量组小鼠肺组织病理状态明显改善,肺组织细胞凋亡水平显著降低,cleaved caspase3、Bax蛋白表达显著降低,Bcl-2蛋白水平增加,炎症因子水平显著降低[IL-6:(817.56±63.49)pg/mL、(529.45±45.67)pg/mL比(964.87±85.12)pg/mL,P<0.05或P<0.01;IL-1β:(83.84±7.69)pg/mL、(64.28±7.06)pg/mL比(127.64±10.98)pg/mL,P均<0.01;TNF-α:(117.22±12.30)pg/mL、(72.69±8.44)pg/mL比(148.74±13.98)pg/mL,P<0.05或P<0.01],肺组织M1型巨噬细胞数量均显著降低,肺组织IRF5 mRNA表达显著下调[(2.59±0.27)、(1.67±0.19)比(3.67±0.34),P<0.05或P<0.01],IRF5蛋白表达显著下调。结论芪冬活血饮可抑制ALI肺组织M1型巨噬细胞募集,减轻炎症反应,其机制可能与抑制IRF5有关。 展开更多
关键词 小鼠 急性肺损伤 芪冬活血饮 干扰素调节因子5 巨噬细胞募集
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IRF5、MUC1水平与IBS患者肠道菌群、胃肠症状严重程度的相关性分析
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作者 沈飞 王超 《浙江临床医学》 2024年第5期657-660,共4页
目的探究血清干扰素调节因子5(IRF5)、黏蛋白1(MUC1)水平与肠易激综合征(IBS)患者肠道菌群、胃肠症状严重程度的相关性,为IBS临床研究提供新的生物学指标。方法选取2022年1月至2023年1月期间本院收治的IBS患者120例,根据IBS诊断标准分为... 目的探究血清干扰素调节因子5(IRF5)、黏蛋白1(MUC1)水平与肠易激综合征(IBS)患者肠道菌群、胃肠症状严重程度的相关性,为IBS临床研究提供新的生物学指标。方法选取2022年1月至2023年1月期间本院收治的IBS患者120例,根据IBS诊断标准分为IBS-C组64例与IBS-D组56例。选择同期本院健康体检者60例为对照组。采用Pearson相关性分析探究血清中IRF5、MUC1水平与肠道菌群的相关性;Spearman相关性分析评估血清IRF5、MUC1表达水平与肠易激综合征症状严重程度量表(IBS-SSS)评分的关系。结果IBS-D组患者血清IRF5表达水平、普氏菌、双歧杆菌数量明显低于IBS-C组和对照组,IBS-C组明显低于对照组;IBS-D组患者MUC1表达水平、肠球菌、大肠杆菌数量明显高于IBS-C组和对照组,IBS-C组明显高于对照组(P<0.05)。与IBS-C组相比,IBS-D组IBS-SSS评分明显升高(P<0.05)。结论IBS患者血清IRF5呈低表达,MUC1呈高表达,二者血清水平与肠道菌群及胃肠症状严重程度具有一定相关性。 展开更多
关键词 肠易激综合征 干扰素调节因子5 黏蛋白1 肠道菌群 胃肠症状严重程度
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抑郁模型大鼠不同脑区5-HT_(1A)蛋白表达及加味温胆汤的干预作用 被引量:2
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作者 张齐 杨瑞 +3 位作者 韦利军 韦海英 高月 武丽 《西部中医药》 2023年第1期8-11,共4页
目的:基于不同脑区5-HT_(1A)蛋白表达,探讨模型大鼠抑郁发病机制以及加味温胆汤的干预作用。方法:将32只SPF级雄性SD大鼠(体质量180~200 g)随机分为正常对照组、抑郁模型组、抑郁中药组、抑郁西药组各8只。采用慢性轻度不可预见性应激... 目的:基于不同脑区5-HT_(1A)蛋白表达,探讨模型大鼠抑郁发病机制以及加味温胆汤的干预作用。方法:将32只SPF级雄性SD大鼠(体质量180~200 g)随机分为正常对照组、抑郁模型组、抑郁中药组、抑郁西药组各8只。采用慢性轻度不可预见性应激制作大鼠抑郁模型,其中正常对照组、抑郁模型组大鼠灌胃生理盐水,抑郁中药组灌胃12 g/kg加味温胆汤,抑郁西药组灌胃1.8 mg/kg百忧解。35天后进行行为学检测及取材,通过Western blot法检测各组大鼠杏仁核、前额皮质、海马CA3区及下丘脑组织中5-HT_(1A)蛋白表达。结果:行为学数据显示,抑郁模型组大鼠水平运动次数、垂直运动次数以及总路程较正常对照组减少(P<0.05),抗抑郁西药百忧解只对总路程有影响(P<0.05),而加味温胆汤能改善模型大鼠抑郁行为表现(P<0.05),提高水平运动、垂直运动次数,延长总路程。抑郁模型组大鼠海马CA3区5-HT_(1A)蛋白表达水平升高,加味温胆汤能降低海马CA3区5-HT_(1A)蛋白表达(P<0.05),百忧解能提高杏仁核5-HT_(1A)蛋白表达(P<0.05)。结论:抑郁模型大鼠不同脑区5-HT_(1A)蛋白表达不一致,抑郁模型大鼠海马CA3区5-HT_(1A)蛋白表达升高,加味温胆汤可能通过降低抑郁模型大鼠海马CA3区5-HT_(1A)蛋白表达发挥抗抑郁作用,而百忧解能提高杏仁核5-HT_(1A)蛋白表达,其抗抑郁机制有待进一步阐明。 展开更多
关键词 抑郁 不同脑区 5-HT_(1A) 升降平调 加味温胆汤 大鼠
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Irf5对肌萎缩侧索硬化细胞模型的毒性作用
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作者 刘亚坤 纪乐 +3 位作者 于利双 李忠尧 李春岩 李媛媛 《脑与神经疾病杂志》 CAS 2023年第3期147-150,共4页
目的观察干扰素调节因子5(interferon-regulatory factor 5,Irf5)对肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS),TDP-25细胞模型的影响。方法利用慢病毒感染的方法,建立过表达Irf5的TDP-25稳转细胞株,在基因及蛋白水平鉴定其表... 目的观察干扰素调节因子5(interferon-regulatory factor 5,Irf5)对肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS),TDP-25细胞模型的影响。方法利用慢病毒感染的方法,建立过表达Irf5的TDP-25稳转细胞株,在基因及蛋白水平鉴定其表达效率,倒置显微镜下观察细胞的形态学变化,通过实时荧光定量PCR方法比较过表达Irf5后对TDP-25细胞的影响,包括细胞凋亡、细胞周期以及炎症因子的产生。结果过表达Irf5后,与细胞凋亡有关的指标Caspase-3、Caspase-8和Bak1都较对照组有所增加。细胞周期调控蛋白,P21的表达增加。炎症因子包括肿瘤坏死因子(tumor necrosis factorα,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-12p40(IL-12p40)的表达都有所增加,与对照组相比,差异有统计学意义。结论Irf5促进TDP-25细胞的凋亡、细胞周期阻滞,以及产生促炎细胞因子,加速了细胞的死亡。 展开更多
关键词 肌萎缩侧索硬化 干扰素调节因子5 细胞凋亡 炎症因子
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自拟安神方对心肾不交证失眠大鼠皮质区和海马区5-HT和DA信号通路影响
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作者 李雪 徐雅 +3 位作者 杜庆红 白俊杰 王旭 李靖 《辽宁中医药大学学报》 CAS 2023年第10期20-25,F0003,共7页
目的探索自拟安神方(简称安神方)对大鼠不同脑区5-羟色胺(5-hydroxytryptamine,5-HT)和多巴胺(dopamine,DA)信号通路的影响,揭示安神方抗大鼠心肾不交证失眠的机制。方法将SD雄性大鼠随机分为正常组,模型组,阳性对照组,安神方高、中、... 目的探索自拟安神方(简称安神方)对大鼠不同脑区5-羟色胺(5-hydroxytryptamine,5-HT)和多巴胺(dopamine,DA)信号通路的影响,揭示安神方抗大鼠心肾不交证失眠的机制。方法将SD雄性大鼠随机分为正常组,模型组,阳性对照组,安神方高、中、低剂量组,每组10只。除正常组外,其他各组采用多因素方法制备改良的心肾不交证失眠大鼠模型,灌胃治疗2周。HE染色观察大鼠脑组织形态结构。高效液相色谱-电化学法(HPLC-ECD)检测大鼠皮质区和海马区DA和5-HT的含量。免疫蛋白印迹法检测5-HT信号通路上5-HT_(1A)受体、5-HT_(2A)受体、磷酸腺苷反应元件结合蛋白(cAMP-response element binding protein,CREB)、蛋白激酶A(protein kinase A,PKA)和DA信号通路上D_(1)R_(1)在皮质区和海马区的蛋白表达。结果HE染色显示模型组皮质区神经元有少量的凋亡,海马结构区变化不明显;安神方组皮质区神经元凋亡有所减轻。HPLC-ECD结果显示,与正常组比较,模型组皮质区和海马区DA含量均升高(P<0.05),5-HT含量均显著下降(P<0.05);与模型组比较,安神方组皮质区和海马区DA含量显著降低(P<0.05),同时海马区5-HT含量有所提高(P<0.05)。免疫印迹结果显示,与正常组比较,模型组皮质区5-HT_(1A)和CREB蛋白表达降低(P<0.05),海马区D_(1)R_(1)蛋白表达升高(P<0.05);与模型组比较,安神方组皮质区5-HT_(1A)和信号通路上关键蛋白CREB的蛋白表达上调(P<0.05),并且海马区D_(1)R_(1)的蛋白表达下调(P<0.05),其信号通路上CREB蛋白表达差异虽无统计学意义,但各给药组仍有上调趋势。结论安神方抗心肾不交证失眠的机制可能与抑制皮质区神经元凋亡,并促进皮质区和海马区5-HT通路功能、抑制DA通路功能有关。 展开更多
关键词 自拟安神方 心肾不交证失眠 不同脑区 多巴胺 5-羟色胺
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Future Precipitation Extremes in China under Climate Change and Their Physical Quantification Based on a Regional Climate Model and CMIP5 Model Simulations 被引量:5
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作者 Peihua QIN Zhenghui XIE +2 位作者 Jing ZOU Shuang LIU Si CHEN 《Advances in Atmospheric Sciences》 SCIE CAS CSCD 2021年第3期460-479,共20页
The atmospheric water holding capacity will increase with temperature according to Clausius-Clapeyron scaling and affects precipitation.The rates of change in future precipitation extremes are quantified with changes ... The atmospheric water holding capacity will increase with temperature according to Clausius-Clapeyron scaling and affects precipitation.The rates of change in future precipitation extremes are quantified with changes in surface air temperature.Precipitation extremes in China are determined for the 21st century in six simulations using a regional climate model,RegCM4,and 17 global climate models that participated in CMIP5.First,we assess the performance of the CMIP5 models and RCM runs in their simulation of extreme precipitation for the current period(RF:1982-2001).The CMIP5 models and RCM results can capture the spatial variations of precipitation extremes,as well as those based on observations:OBS and XPP.Precipitation extremes over four subregions in China are predicted to increase in the mid-future(MF:2039-58)and far-future(FF:2079-98)relative to those for the RF period based on both the CMIP5 ensemble mean and RCM ensemble mean.The secular trends in the extremes of the CMIP5 models are predicted to increase from 2008 to 2058,and the RCM results show higher interannual variability relative to that of the CMIP5 models.Then,we quantify the increasing rates of change in precipitation extremes in the MF and FF periods in the subregions of China with the changes in surface air temperature.Finally,based on the water vapor equation,changes in precipitation extremes in China for the MF and FF periods are found to correlate positively with changes in the atmospheric vertical wind multiplied by changes in surface specific humidity(significant at the p<0.1 level). 展开更多
关键词 precipitation extremes regional climate model CMIP5 models
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Future temperature changes over the critical Belt and Road region based on CMIP5 models 被引量:3
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作者 DONG Tian-Yun DONG Wen-Jie +4 位作者 GUO Yan CHOU Jie-Ming YANG Shi-Li TIAN Di YAN Dong-Dong 《Advances in Climate Change Research》 SCIE CSCD 2018年第1期57-65,共9页
Based on data of 22 models from the Coupled Model Inter-comparison Project Phase 5(CMIP5),the performance of climate simulation is assessed and future changes under RCP2.6,RCP4.5 and RCP8.5 are projected over critical... Based on data of 22 models from the Coupled Model Inter-comparison Project Phase 5(CMIP5),the performance of climate simulation is assessed and future changes under RCP2.6,RCP4.5 and RCP8.5 are projected over critical Belt and Road region.Compared with observations,the CMIP5 models simulate the linear trend and spatial distribution of the annual mean surface air temperature(SAT)better in the north(NBR)and south(SBR)of the Belt and Road region.The trend of the 22-model ensemble mean(CMIP5 MME)is 0.70/0.50 C per 100 years from 1901 to 2005,and the observed trend is 1.11/0.77 C per 100 years in the NBR/SBR region.After 1971,the relative error between CMIP5 MME and observations is 22%/15%in the NBR/SBR region.Seven/nine models are selected in the NBR/SBR to project future SAT changes under three RCP scenarios.For 2081e2100,warming in the NBR/SBR is projected to be(1.16±0.29)/(0.72±0.32)C,(2.41±0.54)/(1.55±0.44)C,and(5.23±1.02)/(3.33±0.65)C for RCP2.6,RCP4.5,and RCP8.5,respectively.Under the RCP scenarios,the NBR region shows greater warming than the SBR region.The most significant warming is expected in Kazakhstan and the northern part of the SBR.The associated uncertainty generally increases with time under the three RCP scenarios.Furthermore,increases in warming over the Belt and Road region are more remarkable under higher-emission scenarios than lower-emission ones. 展开更多
关键词 CMIP5 MODELS The BELT and ROAD region Temperature PROJECTION RCPs
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Projected changes in mean and extreme climates over Hindu Kush Himalayan region by 21 CMIP5 models 被引量:4
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作者 WU Jie XU Ying GAO Xue-Jie 《Advances in Climate Change Research》 SCIE CSCD 2017年第3期176-184,共9页
Based on the outputs from 21 CMIP5 (Coupled Model Intercomparison Project phase 5) models, future changes in the mean temperature, precipitation and four climate extreme indices (annual maximum of daily maximum temper... Based on the outputs from 21 CMIP5 (Coupled Model Intercomparison Project phase 5) models, future changes in the mean temperature, precipitation and four climate extreme indices (annual maximum of daily maximum temperature (TXx), minimum of daily minimum temperature (TNn), annual total precipitation when the daily amount exceeds the 95th percentile of wet-day precipitation (R95p), and maximum consecutive 5-day precipitation (RX5day)) over Hindu Kush Himalayan (HKH) region are investigated under the greenhouse gas concentration pathways of RCP4.5 and RCP8.5. Two periods of the 21st century, 2036e2065 and 2066e2095, are selected, with the reference period is considered as 1976e2005. Results show general increase of the mean temperature, TXx and TNn under both scenarios, with the largest increases found during 2066e2095 under RCP8.5. Future precipitation is projected to increase over most part of HKH, except for the northwestern part. Intensification of the precipitation extremes is projected over the region. The uncertainties of mean temperature, TXx and TNn over the HKH1 subregions are the largest compared to the other three subregions and the overall HKH. Besides RX5day during 2036e2065 over HKH1, the uncertainties of R95p and RX5day tend to be larger following the increase of greenhouse gas concentrations. The multimodel ensemble medians of temperature and four extreme indices under RCP8.5 are projected to be larger than those under RCP4.5 in each of the subregions. 展开更多
关键词 HINDU Kush HIMALAYAN region CMIP5 Mean CLIMATE EXTREME CLIMATE EVENTS CLIMATE change PROJECTION
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Association of rs10954213 Polymorphisms and Haplotype Diversity in Interferon Regulatory Factor 5 with Systemic Lupus Erythematosus: A Meta-analysis 被引量:1
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作者 刘辉峰 安湘杰 +5 位作者 杨艳 杨柳 李延 黄长征 陶娟 涂亚庭 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2013年第1期15-21,共7页
The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 (1RF5) play a special role in systemic lupus erythematosus (SLE) but with inconclusive results. We conducted a meta-analysi... The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 (1RF5) play a special role in systemic lupus erythematosus (SLE) but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence interval (95% CI). A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results in- dicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rS10954213 G allele (A vs. G, P〈0.00001) in all subjects. The same pattern of the results was also ob- tained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele (49.1%) than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele (62.1%). The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 (P=0.002). The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 (P=-0.004). This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype (rs2004640-rs2070197-rs10954213) in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent. 展开更多
关键词 gene polymorphism META-ANALYSIS systemic lupus erythematosus interferon regulatory factor 5
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Functional characterization of a Δ6 fatty acid desaturase gene and its 5′-upstream region cloned from the arachidonic acid-rich microalga Myrmecia incisa Reisigl(Chlorophyta) 被引量:1
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作者 张利 曹海生 +1 位作者 宁璞 周志刚 《Journal of Oceanology and Limnology》 SCIE CAS CSCD 2018年第6期2308-2321,共14页
It is suggested that Δ6 fatty acid desaturase(FAD) plays a critical role in the biosynthesis of polyunsaturated fatty acids in plants and microalgae. But why does it adapt to the changed environments such as nitrogen... It is suggested that Δ6 fatty acid desaturase(FAD) plays a critical role in the biosynthesis of polyunsaturated fatty acids in plants and microalgae. But why does it adapt to the changed environments such as nitrogen starvation is seldom understood. One Δ6 FAD gene( MiD6 fad) from an arachidonic acidrich microalga M yrmecia incisa Reisigl(Chlorophyta) was first heterologously expressed in S accharomyces cerevisiae for the identification of function. The fatty acid profile of transgenic yeast detected by gas chromatography-mass spectrometry illustrated that the enzyme MiD6 FAD could convert linoleic and ?-linolenic acids to γ-linolenic and stearidonic acids, respectively, demonstrating that M iD6 fad encoded a Δ6 FAD. A 1 965-bp fragment of the cloned 2 347-bp 5′-upstream region of M iD6 fad was next subcloned and fused upstream with green fluorescent protein(GFP) gene to replace the GAL1 promoter of the vector pYES2. The generated construct was transformed into S. cerevisiae for function determination. Confocal microscopic images of the transformed line illustrated that this inserted fragment could drive GFP expression, which was further verified by fluorescence intensity quantification and Western blot analysis using antiGFP antibody. The conversion efficiency(approximately 2%-3%) of MiD6 FAD was much lower than the reported ? 3 FAD and Δ6 elongase in this microalga, suggesting that MiD6 FAD catalysed the possible ratelimiting step for ArA biosynthesis. The presence of several putative c is-acting regulatory elements in this identified promoter sheds new light on the regulation mechanism research of Δ6 FAD transcription for the ArA production in M. incisa in changing environmental factors. 展开更多
关键词 arachidonic acid(ArA) fatty ACID desaturase(FAD) green fl uorescent protein(GFP) green MICROALGA Saccharomyces cerevisiae 5′-upstream region(5′-USR)
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The hepatitis C virus 5’ untranslated region gene amplified by rapid amplification of cDNA ends and its secondary structure 被引量:1
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《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2002年第3期368-372,共5页
Objectives: To obtain very end full-length cDNA ofhepatitis C virus (HCV) 5’ untranslated region(5’UTR) and analyze its primary and secondarystructure.Methods: A patient infected genotype 2a HCV wasidentified by rev... Objectives: To obtain very end full-length cDNA ofhepatitis C virus (HCV) 5’ untranslated region(5’UTR) and analyze its primary and secondarystructure.Methods: A patient infected genotype 2a HCV wasidentified by reverse transcription-nested polymerasechain reaction (RT-PCR) and restriction fragmentlength polymorphism (RFLP). Total RNA isolatedfrom the serum was used as template, and the cDNAof the 5’ untranslated region was amplified using rap-id amplification of cDNA ends (RACE). The frag-ments were recombinated by A-T clone strategy, andthe recombinants were confirmed by RFLP andPCR, and sequenced subsequently. Secondary struc-tures were analysed by RNAdraw.Results: Very end full-length cDNA of genotype 2aHCV 5’ UTR was obtained by RACE. In five clonesobtained, three contained full-length 5’UTR cDNA;A21G, G170A, T222C, T247C, C339T substitutionswere found as compared to HC-J6. Homological re-sults of HCV-1, HC-J6, HC-C2, HC-J8 were 93.6%-94.4%, 92.1%-93%, 98.8%-99.7%, 96.2%-96.5%, respectively; however, the substitutions didnot alter secondary structure. Two of 5 clones weredeletions of 53bp and 135bp at the 5’terminal ofHCV 5’UTR, respectively.Conclusions: RACE can be used to obtain the full-length cDNA of 2a genotype HCV 5’UTR. Genes de-leted at the 5’ terminal of HCV circulate in hepatitisC patients. 展开更多
关键词 HEPATITIS C 5 untranslated region SEQUENCE analysis rapid AMPLIFICATION CDNA ENDS
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Geochemical Characteristics of C_5–C_7 Light Hydrocarbons in Gas Hydrates from the Permafrost Region of Qilian Mountains 被引量:2
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作者 ZHANG Min KONG Ting HE Yu 《Acta Geologica Sinica(English Edition)》 SCIE CAS CSCD 2016年第6期2283-2284,共2页
As an important part of gas hydrates, light hydrocarbons (LHs), especially C5 to C7 hydrocarbons with various monomer compounds, provide a wide variety of geological and geochemical information, which have received ... As an important part of gas hydrates, light hydrocarbons (LHs), especially C5 to C7 hydrocarbons with various monomer compounds, provide a wide variety of geological and geochemical information, which have received much attention from organic geochemists and petroleum geologists. 展开更多
关键词 Geochemical Characteristics of C5 C7 Light Hydrocarbons in Gas Hydrates from the Permafrost region of Qilian Mountains
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