胰岛素诱导Zucker肥胖大鼠肾小球系膜细胞核因子-κB活性的变化

目的 研究胰岛素(INS)对体外培养的Zucker大鼠肾小球系膜细胞(GMC)核因子κB(NF-κB)活化的影响,以及INS诱导的NF-κB活性的变化与Zucker大鼠年龄(即病程)以及基因型的相关性。方法 (1)分别取Zucker肥胖大鼠(3月龄和10月龄)和Zucker瘦型大鼠(3月龄和10月龄)4组大鼠的GMCs(O_(3m),O_(10m),L_(3m),L_(10m))进行传代培养。(2)凝胶迁移率实验(EMSA)和超迁移率实验(GSA)检测不同浓度及不同时相INS对Zucker大鼠肾小球系膜细胞NF-κB活性的影响,以及NF-κB二聚体中p50和p65成分的变化。(3)应用Western印迹检测胞浆和胞核内NF-κB p65水平。结果 (1)INS诱导后,4组GMC内NF-κB活性均较对照组明显增强(F=219.65,P<0.01);(2)随着INS刺激浓度增加和时间的延长,GMC内NF-κB活性相应增强,0.5 mg/L的INS刺激24h时,NF-κB活性强度达最高峰;INS刺激浓度升为5 mg/L,则15h达最高峰;(3)INS主要激活NF-κB二聚体成份中的p65;(4)O_(3m)组NF-κB的活性显著高于O_(10m)组(P<0.01),L_(3m)组NF-κB的活性显著高于L_(10m)组(P<0.01),O_(3m)组显著高于L_(3m)组(P<0.01),O_(10m)组显著高于L_(10m)组(P<0.01)。(5)INS可呈剂量依赖性地降低胞浆内的p65的蛋白水平和上调胞核内p65水平。结论 INS可诱导Zucker大鼠GMC内NF-κB活化,其活化方     

Is it safe to use TNF-α blockers for systemic inflammatory disease in patients with heart failure? Importance of dosage and receptor specificity

Tumor necrosis factor-alpha (TNF-α) blockers are widely used in the treatment of chronic inflammatory diseases, especially chronic arthritis. Current guidelines advise against the use of such agents in patients who have a concomitant heart failure. Consequently, a group of patients with a devastating inflammatory disease cannot benefit from an excellent treatment option. After a critical review of the current literature, we conclude that there is not sufficient evidence to warn against such a regimen if recommended standard doses are used. A negative effect on the heart function seems to occur if unconventional high doses of TNF-α blockers are given. The theoretical background for this is discussed.     

大黄素抗炎作用及对急性肺损伤治疗作用研究进展

[目的]探讨大黄素抗炎作用及其对急性肺损伤的治疗作用。[方法]通过查阅PUBMED、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、万方数据库和维普数据库汇总1998-2012年间的相关文献,总结归纳大黄素的抗炎作用和机制,以及其对急性肺损伤的治疗作用。[结果]多种体内外研究都证实大黄素具有抗炎作用,其抗炎机制与抑制NF-κB活化、调节多种炎症因子等相关。另外,大黄素对急性肺损伤的治疗作用在细胞及动物水平得到肯定。[结论]大黄素有良好的临床应用前景。     

Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging

Innate and adaptive immunity are the major defence mechanisms of higher organisms against inherent and environmental threats. Innate immunity is present already in unicellular organisms but evolution has added novel adaptive immune mechanisms to the defence armament. Interestingly, during aging, adaptive immunity significantly declines, a phenomenon called immunosenescence, whereas innate immunity seems to be activated which induces a characteristic pro-inflammatory profile. This process is called inflamm-aging. The recognition and signaling mechanisms involved in innate immunity have been conserved during evolution. The master regulator of the innate immunity is the NF-kB system, an ancient signaling pathway found in both insects and vertebrates. The NF-kB system is in the nodal point linking together the pathogenic assault signals and cellular danger signals and then organizing the cellular resistance. Recent studies have revealed that SIRT1 (Sir2 homolog) and FoxO (DAF-16), the key regulators of aging in budding yeast and Caenorhabditis elegans models, regulate the efficiency of NF-kB signaling and the level of inflammatory responses. We will review the role of innate immunity signaling in the aging process and examine the function of NF-kB system in the organization of defence mechanisms and in addition, its interactions with the protein products of several gerontogenes. Our conclusion is that NF-kB signaling seems to be the culprit of inflamm-aging, since this signaling system integrates the intracellular regulation of immune responses in both aging and age-related diseases.     

Breast adenocarcinoma MCF-7 cell line induces spontaneous osteoclastogenesis via a RANK-ligand-dependent pathway

The metastasis of breast cancer to the skeleton is a serious clinical problem resulting in hypercalcemia, bone fragility and insurmountable pain. The invasion of bony tissue by neoplastic cells usually very rapidly affects the balance between bone apposition and bone resorption. In order to elucidate a mechanism for cancer-induced osteoclastogenesis, cells from a human breast cancer line, MCF-7, were directly co-cultured with murine monocytes RAW 264.7 type CRL 2278. Compared with controls, co-culture of MCF-7 induced differentiation of multinucleated cells by membrane-bound and soluble receptor activator of NF-kB ligand (RANKL) as quantified by ELISA, Western blot analysis, transmission electron microscopy (TEM), and immunocytochemistry. The aim of this study was to determine an in vitro model system of MCF-7 human breast cancer cells grown together with monocytes to show that expression of RANKL promotes osteoclastogenesis, which may indicate a mechanism for the development of osteolytic lesions in breast cancer bone metastasis.     

Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism

Diffuse large B-cell lymphoma (DLBCL) is the most common type of adult lymphoma. It is a group of malignant tumors with a large number of clinical manifestations and prognoses. Therefore, it is necessary to explore its unknown potential therapeutic targets. Histone deacetylase inhibitor (HDACi) is a novel drug for the treatment of DLBCL, however pan-HDACis cannot be ignored because of their clinical efficacy. By contrast, specific HDACi is well-tolerated, and LMK-235 is a novel HDACi that is a specific inhibitor of HDAC4 and HDAC5. In this study, we investigated the up-regulation of BCLAF1 through NF-κB signaling pathways in LMK-235, mediating the apoptosis of two diffuse large B-cell lymphoma cell lines, OCI-LY10 and OCI-LY3. Further studies showed that BCLAF1 expression was increased in DLBCL cells after treatment with the NF-κB inhibitor Bay11-7082. The combination of Bay11-7082 and siRNA si-HDAC4 significantly increased BCLAF1 expression and further increased apoptosis. These results indicate that BCLAF1 plays an important role in LMK-235-mediated apoptosis and may be a potential target for the treatment of diffuse large B-cell lymphoma.     

NF-κB在右美托咪定抑制利多卡因神经毒性中的作用

目的探讨核转录因子-κB（NF-κB）在右美托咪定（Dex）抑制利多卡因对坐骨神经分支损伤（SNI）模型大鼠脊髓神经毒性中作用。方法取40 只SD雄性大鼠,随机分为5 组：健康对照组（C 组）、SNI 模型组（S 组）、SNI利多卡因组（SL 组）、SNI 利多卡因+Dex 组（SLD组）、SNI 利多卡因+Dex+NF-κB 阻断剂组（SLDB 组）,每组8 只大鼠。所有大鼠行硬膜外置管,C 组未做其他处理。在疼痛稳定后,S 组鞘内注射生理盐水20 μl,SL组鞘内注射10%利多卡因20 μl,SLD 组在SL组基础上腹腔注射75 μg/kg Dex,SLDB 组在SLD 组基础上鞘内注射40μg 吡咯烷二硫代氨基甲酸酯。连续药物处理7 d 后取各组大鼠L4～6节段脊髓,透射电镜观察脊髓形态;末端标记法荧光染色观察脊髓背角细胞凋亡;Western blot检测Bax 和Caspase-1 表达量;酶联免疫吸附法检测各组脊髓匀浆液中TNF-α和IL-1β的表达。结果①与S 组比较,SL组、SLD 组及SLDB 组的机械痛阈值升高,细胞凋亡数、Bax、Caspase-1、TNF-α及IL-1β表达增加（p <0.05）;②与SL 组比较,SLD组和SLDB 组细胞凋亡数、Bax、Caspase-1、TNF-α及IL-1β表达降低（p <0.05）;③与SLD 组比较,SLDB 组细胞凋亡数、Bax、Caspase-1、TNF-α及IL-1β表达增加（p <0.05）。结论Dex 抑制利多卡因对SNI模型大鼠脊髓神经毒性可能与激活NF-κB 通路、抑制炎症及凋亡有关。     

慢性心衰患者NT pro BNP、NF-kB、Hs-CRP联合检测临床意义

目的 观察NT pro BNP、NF-kB、Hs-CRP联合检测对慢性心衰患者的诊断价值.方法 收集92例慢性心衰患者的临床资料,其中心功能(NYHA)Ⅱ级29例,Ⅲ级32例,Ⅳ级31例,另选35例作为健康对照组进行对比分析,检测各组患者NT pro BNP、NF-kB、Hs-CRP水平.结果 心衰组不同心功能分级的患者的NT pro BNP、NF-kB、Hs-CRP水平均高于对照组(P＜0.05),并伴随心功能损伤程度增幅而显著增高.心衰组NT pro BNP、NF-kB、Hs-CRP单项阳性检出率均明显低于联合检测阳性率,差异有统计学意义(P＜0.05).NT pro BNP与NF-kB、Hs-CRP呈正相关(r=0.587、0.519,P＜0.05).结论 NT pro BNP、NF-kB、Hs-CRP水平变化能动态反应心衰患者心功能损伤程度,联合检测可提高心衰患者心功能病变阳性检出率.     

AK092375通过膀胱癌GLUT3的表达对NF-κB/TCS2/mTOR信号通路相关因子的影响

目的 观察长链非编码RNA(lncRNA)AK092375在膀胱癌细胞中的表达及其通过葡萄糖转运蛋白3(GLUT3)的表达对NF-κB/TCS2/mTOR信号通路相关因子的影响.方法 2020年1月—2021年5月于内蒙古医科大学附属医院临床医学研究中心进行相关实验.选择AK092375表达量最低的膀胱癌细胞系T24作...