Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling

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亲脂素增加血管平滑肌细胞的脂质集聚

目的 观察乙酰化的低密度脂蛋白(AcLDL)对血管平滑肌细胞亲脂素(adipophilin)表达的影响及亲脂素对血管平滑肌细胞的AcLDL摄取及脂质集聚的影响.从而探讨其在糖尿病大血管病变发生中的作用.方法 以不同浓度AcLDL干预人血管平滑肌细胞(HVSMCs).应用Northern印迹及Western印迹技术检测AcLDL对亲脂素表达的影响;以RNA干扰技术、流式细胞仪、酶法和油红O染色检测亲脂素对HVSMCs的脂质集聚及AcLDL摄取的影响.结果 AcLDL呈剂量依赖性地增加HVSMCs的亲脂素的表达,沉默亲脂素基因使HVSMCs对AcLDL的摄取(降低38.7%,P<0.05)和脂质集聚能力下降(甘油三酯、总胆固醇分别下降30.6%和29.8%,均P<0.01).结论 亲脂素促进HVSMCs摄取AcLDL,增加HVSMCs脂质集聚,这可能是亲脂素促进动脉粥样硬化的机制之一.     

Sirt1在急性炎症状态下糖尿病小鼠肾损伤中的作用

目的 探究Sirt1在急性炎症状态下糖尿病小鼠肾损伤中的作用及分子机制。方法选择SPF级C57BL/6J雄性小鼠40只,8周龄,体重20～25 g。采用随机数字表法将小鼠分为五组：对照组(C组)、糖尿病组(D组)、脂多糖(LPS)+糖尿病组(L组)、LPS+糖尿病+Sirt1阻断剂EX527组(E组)和LPS+糖尿病+Sirt1激动剂银杏黄酮苷元组(G组),每组8只。糖尿病小鼠模型制备成功后,L组腹腔注射LPS 10 mg/kg; E组在糖尿病小鼠给予LPS处理前1 h腹腔注射EX527 5 mg/kg(溶于DMSO 0.2 ml);G组在糖尿病小鼠给予LPS处理前1 h腹腔注射银杏黄酮苷元200 mg/kg(溶于DMSO 0.2 ml);C组和D组在相同时点腹腔注射2%DMSO 0.15 ml。收集24 h尿液测定24h尿量和24 h尿蛋白浓度,眼球取血检测血清肌酐(Scr)和尿素氮(BUN)浓度。取肾组织后采用ELISA法检测IL-1β、IL-18浓度,硝酸还原酶法检测一氧化氮(NO)含量,铁离子抗氧化能力法检测总抗氧能力(T-AOC),qPCR和Western blot法检测Si...     

曲古菌素A在胃腺癌细胞系SGC-7901中的作用

目的研究曲古菌素A（TSA）在胃腺癌细胞系SGC-7901中的作用。方法四甲基偶氮唑蓝法测定TSA对SGC-7901的细胞毒性，荧光显微镜观察细胞核DNA的变化，流式细胞仪检测细胞周期和凋亡率，Western印迹检测组蛋白H3的乙酰化状态。结果SGC-7901细胞生长曲线表明，TSA浓度增高，细胞生长率下降。细胞凋亡率在75ng／mlTSA作用72h时与对照组比较，差异有统计学意义（P〈0．05）。凋亡细胞DNA变化主要表现为核染色质固缩及断裂，荧光染色增强。流式细胞仪分析出现明显的亚G1期峰，G1期细胞减少，细胞凋亡率达29．54％。TSA作用后，乙酰化的组蛋白如明显增多。结论TSA可以诱导SGC-7901细胞发生凋亡，组蛋白H3的乙酰化状态可能与细胞凋亡有关。     

Berberine inhibits the expression of TNFα, MCP-1, and IL-6 in AcLDL-stimulated macrophages through PPARγ pathway

Macrophages are the main source of cytokines in atherosclerotic plaques. Modified low-density lipoproteins may stimulate macrophages to produce large quantities of proinflammatory cytokines that promote atherosclerosis. Berberine is the main component of the traditional Chinese medicine umbellatine, which has a widespread effect and was used to treat many diseases clinically. Our previous study found that berberine could increase adipophilin expression in macrophages, which is a target gene of PPARγ. PPARγ agonist could decrease proinflammatory cytokines in macrophage. In this study, we investigated the effects and the mechanism of action of berberine on the expression and secretion of TNFα, MCP-1, and IL-6 in vitro to identify new pharmacological actions of berberine. The results of RT-PCR and ELISA shows that berberine may inhibit the expression and secretion of the tumor necrosis factor α (TNFα), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6) in macrophages stimulated by acetylated low-density lipoprotein (AcLDL), whereas the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor GW9662 could attenuate this effect of berberine. This study demonstrates that berberine may inhibit the expression and production of TNF-α, MCP-1, and IL-6 in AcLDL-stimulated macrophages. This effect might be partially mediated through PPARγ activity.     

亲脂素增加血管平滑肌细胞的脂质集聚

目的 观察乙酰化的低密度脂蛋白(AcLDL)对血管平滑肌细胞亲脂素(adipophilin)表达的影响及亲脂素对血管平滑肌细胞的AcLDL摄取及脂质集聚的影响.从而探讨其在糖尿病大血管病变发生中的作用.方法 以不同浓度AcLDL干预人血管平滑肌细胞(HVSMCs).应用Northern印迹及Western印迹技术检测AcLDL对亲脂素表达的影响;以RNA干扰技术、流式细胞仪、酶法和油红O染色检测亲脂素对HVSMCs的脂质集聚及AcLDL摄取的影响.结果 AcLDL呈剂量依赖性地增加HVSMCs的亲脂素的表达,沉默亲脂素基因使HVSMCs对AcLDL的摄取(降低38.7%,P<0.05)和脂质集聚能力下降(甘油三酯、总胆固醇分别下降30.6%和29.8%,均P<0.01).结论 亲脂素促进HVSMCs摄取AcLDL,增加HVSMCs脂质集聚,这可能是亲脂素促进动脉粥样硬化的机制之一.     

Salvianolic acid B alleviates oxidative stress in non-alcoholic fatty liver disease by mediating the SIRT3/FOXO1 signaling pathway

Salvianolic acid B (Sal B) is a polyphenolic antioxidant that has been shown to have anti-lipid accumulation, anti-inflammatory, and free oxygen radical scavenging activities in various diseases. Here, we aimed to examine whether Sal B could alleviate non-alcoholic fatty liver disease (NAFLD) and explore the possible mechanisms. Signaling pathways involved in oxidative stress, including SIRT3, SOD2, and FOXO1 pathways, were investigated by Western blotting analysis, RT-qPCR, and immunoprecipitation (IP). In the present study, oleic acid (OA) successfully induced lipid and peroxide accumulation, decreased SIRT3 expression, and increased FOXO1 acetylation. However, Sal B significantly reversed these trends. SIRT3 plasmid transfection further reduced the expression of acetylated FOXO1 and considerably enhanced the regulation of SIRT3 and acetylated FOXO1 induced by Sal B. Following SIRT3 siRNA transfection, Sal B-induced down-regulation of acetylated FOXO1 was blocked, suggesting that Sal B-mediated protection occurred through SIRT3-mediated FOXO1 deacetylation. The SIRT3/FOXO1 pathway was a critical therapeutic target for controlling oxidative stress in NAFLD, and Sal B conferred protection against OA-induced hepatic steatosis and oxidative stress through SIRT3-mediated FOXO1 deacetylation.     

大黄素乙酰化物致鼻咽癌 CNE-1 细胞线粒体自噬活性的研究

目的研究大黄素乙酰化物作用鼻咽癌CNE-1细胞后,其线粒体损伤及其与线粒体自噬的关系。方法以5mg·L^-1及10mg·L^-1大黄素乙酰化物作用鼻咽癌CNE-1细胞,通过透射电镜观察大黄素乙酰化物导致鼻咽癌CNE-1细胞自噬体形成的超微结构;激光共聚焦显微镜测定线粒体膜电位、细胞内钙离子、细胞内活性氧的浓度变化及线粒体自噬的活性。结果与空白对照组比较,两个实验组细胞都出现线粒体损伤以及线粒体自噬体。大黄素乙酰化物作用后的细胞线粒体膜电位降低（P〈0．05）;细胞内游离的钙离子浓度升高（P〈0．05）;细胞内活性氧增加（P〈0．05）,且呈剂量依赖性。经线粒体与溶酶体示踪分析,可见大黄素乙酰化物作用的实验组均出现酸性溶酶体增殖,其中包含线粒体探针标记的线粒体碎片等典型的自噬特征,且增加的趋势呈剂量效应关系。结论大黄素乙酰化物可致鼻咽癌CNE-1细胞线粒体损伤,并与线粒体自噬密切相关。     

Evaluation of chemically modified hydrophobic sago starch as a carrier for controlled drug delivery

The present investigation deals with the development of controlled release tablets of lamivudine using acetylated sago starch. The acetylated starch was synthesized with acetic anhydride in pyridine medium. The acetylated sago starch was tested for acute toxicity and drug–excipient compatibility study. The formulations were evaluated for physical characteristics like hardness, % friability, % drug content and weight variations. The in vitro release study showed that the optimized formulation exhibited highest correlation (R) value in the case of higuchi kinetic model and the release mechanism study proved that the formulation showed a combination of diffusion and erosion processes. There was a significant difference in the pharmacokinetic parameters (T_max, C_max, AUC, V_d, T_1/2 and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir® which proves the controlled release property of acetylated sago starch.     

Migration of Acetylated Hemicellulose from Capillary Hemodialyzer to Blood, Causing Scleritis and/or Iritis

From November 1981 to early March 1982, an outbreak of scleritis and/or iritis occurred among patients treated with a Nipro brand NAC series cellulose acetate capillary dialyzer. The rate of incidence with dialyzers produced in 1982 was significantly higher than that with dialyzers produced in 1981. An extract obtained from the dialyzers caused iritis in rabbits after its infusion into an auricula vein. Glycerol, acetylated carbohydrate (AC) derivatives, urethane derivatives, and polypropyleneglycol were found in the extract. AC derivatives caused iritis in rabbits, whereas they caused hyperemia of the bulbar conjunctiva in dogs. The AC derivatives contained xylose and glucose units in a ratio of 1.6-2.3:1. The amounts of AC derivatives were significantly larger in the extracts from 1982 than from 1981 devices. Moreover, another brand, but the same type, of dialyzer, the Cordis Dow 4000, contained a slight amount of them. These facts show that AC derivatives derived from hemicellulose played a primary role in the outbreak.