芍药苷联合奥沙利铂对肠癌细胞增殖和凋亡的影响

目的：观察芍药苷联合奥沙利铂对人结肠癌细胞SW480体外增殖及凋亡的影响,初步探讨其作用机制.方法：MTT法检测芍药苷、奥沙利铂单药及联合用药对结肠癌细胞SW480增殖抑制的影响,流式细胞仪检测细胞凋亡率,Western blot检测Bcl-2蛋白表达,ELISA检测细胞核内NF-κB转录活性.结果：芍药苷及奥沙利铂呈浓度依赖性抑制SW480细胞生长,两药联合具有协同抑制作用（P＜0.05）;联合用药组细胞凋亡率为（34.2±1.43）％,明显高于芍药苷单药组（10.2±0.16）％及奥沙利铂单药组（22.3±0.22）％（P＜0.05）;Western blot法检测表明芍药苷能够显著抑制Bcl-2蛋白的表达（P＜0.05）;ELISA法检测表明,与对照组（2.013±0.04）比较,芍药苷单药组（1.17±0.17）及联合用药组（0.9±0.08）吸光值明显降低（P＜0.05）.结论：芍药苷能显著提高奥沙利铂的抗肿瘤作用,此协同作用主要是通过抑制NF-κB的转录活性,从而下调Bcl-2的蛋白表达,促进肿瘤细胞凋亡来实现的.     

CDA-2抑制肺癌生长的炎症机制研究

目的探究尿多酸肽（CDA-2）抑制肺癌生长的作用及炎症机制。方法通过给雌性C57BL/6小鼠尾静脉注射LLC细胞,建立小鼠肺癌模型。采用肿瘤计数和测量大小评价CDA-2对肺肿瘤增殖的影响;收集经CDA-2治疗过的小鼠肺支气管肺泡灌洗液（BALF）并分离肺泡巨噬细胞,采用白细胞分类计数、电泳迁移位移试验（EMSA）、ELISA试验,研究CDA-2抑制肿瘤的作用机制。结果与对照相比,CDA-2明显抑制小鼠肺肿瘤的生长,肿瘤数和肿瘤尺寸显著下降（P〈0.05）。经CDA-2处理后支气管肺泡灌洗液（BALF）的巨噬细胞中的NF-κB与靶DNA结合的活性被强烈的抑制。此外,CDA-2处理显著减少BALF中各种炎性细胞的数量（P〈0.05）,以及炎症因子TNFα,IL-6,KC在肺组织中的表达（P〈0.05）。结论 CDA-2能抑制肺肿瘤的生长,通过抑制髓系细胞中NF-κB的活性,减少肺部炎症,可能是CDA-2抑制肺癌的生长的机制。     

核因子-κB p65在宫颈癌组织中的表达及意义

 目的　探讨NF κBp6 5蛋白在宫颈鳞癌及宫颈腺癌组织中表达的意义。 方法　采用免疫组织化学方法 ,用NF κBp6 5单克隆抗体检测 6 4例宫颈鳞癌组织 ,6例宫颈腺癌组织 ,11例宫颈上皮内瘤样病变 (CIN)组织 ,16例慢性宫颈炎组织中NF κBp6 5的表达。 结果　NF κBp6 5在宫颈鳞癌和腺癌中的阳性表达明显高于CIN和慢性宫颈炎组织 ,有淋巴转移的癌组织中NF κBp6 5的阳性表达率高于无淋巴转移的癌组织。结论　NF κBp6 5蛋白在宫颈癌的发生发展中起重要作用     

Identification of biomarkers for essential hypertension based on metabolomics

AimEssential hypertension (EH) is one of the most important public health problems worldwide. However, the pathogenesis of EH is unclear and early diagnostic methods are lacking. Metabolomics demonstrates great potential for biomarker discovery and the mechanistic exploration of metabolic diseases.Data synthesisThis review included human and animal metabolomics studies related to EH in the PubMed and Web of Science databases between February 1996 and May 2020. The study designs, EH standards, and reported metabolic biomarkers were systematically examined and compared. The pathway analysis was conducted through the online software MetaboAnalyst 4.0.Twenty-two human studies and fifteen animal studies were included in this systematic review. There were many frequently reported biomarkers with consistent trends (e.g., pyruvate, lactic acid, valine, and tryptophan) in human and animal studies, and thus had potential as biomarkers of EH. In addition, several shared metabolic pathways, including alanine, aspartate, and glutamate metabolism, aminoacyl-tRNA biosynthesis, and arginine biosynthesis, were identified in human and animal metabolomics studies. These biomarkers and pathways, closely related to insulin resistance, the inflammatory state, and impaired nitric oxide production, were demonstrated to contribute to EH development.ConclusionsThis study summarized valuable metabolic biomarkers and pathways that could offer opportunities for the early diagnosis or prediction of EH and the discovery of the metabolic mechanisms of EH.     

脑梗死合并肺部感染患者TNF-α、HMGBl、TLR4-NF-κB信号通路改变研究

目的探究脑梗死合并肺部感染患者的肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)和高迁移率族蛋白Bl(High mobility group protein Bl,HMGBl)水平及其临床价值研究。方法2018年1月-2019年2月儋州市人民医院收治的急性脑梗死患者作为研究对象,其中急性脑梗死合并肺部感染患者30例作为感染组,急性脑梗死无肺部感染患者80例作为非感染组,选择同期于此医院体检的健康者30名作为对照组。采用酶联免疫吸附法(Enzyme-linked immuno sorbent assay,ELISA)检测血清HMGB1和细胞因子IL-6、TNF-α水平,采用Western Blot法检测血清Toll样家族受体-4(Toll like receptor-4,TLR4)、核因子κB(nuclear factor kappa-B,NF-κB)、髓样分化因子(myeloiddifferentiationfactor88,MyD88)表达水平。结果感染组的血清HMGB1、TLR4、NF-κB、MyD88表达及细胞因子IL-6、TNF-α水平均高于非感染组和对照组(P<0.05);感染组患者大梗死灶、中等梗死灶、小梗死灶各指标总体水平差异具有统计学意义(P<0.05)。大梗死灶、中等梗死灶两亚组患者的血清HMGB1、TLR4、NF-κB、MyD88表达及细胞因子IL-6、TNF-α水平均高于小梗死灶亚组(P<0.05);急性脑梗死合并肺部感染患者的血清HMGB1和TNF-α水平呈正相关(r=0.523,P<0.001)。结论脑梗死合并肺部感染患者伴随TNF-α、HMGBl、TLR4-NF-κB信号通路的明显改变,且与梗死灶大小具有相关性,其机制有待进一步研究。     

Nanomedicine for acute respiratory distress syndrome: The latest application,targeting strategy,and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air–blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.     

Eupartoium makinoi suppresses lipopolysaccharide-induced inducible nitric oxide synthase and cyclooxygenase-2 expression

Inflammation is involved in numerous diseases including cancer. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) play important roles in the development of certain inflammatory diseases. Eupatorium makinoi, which belongs to a family of Asteraceae plants, is used medicinally in East Asia. We investigated the effects of an ethanol extract of E. makinoi (EEM) on nuclear factor-kappa B (NF-κB) activation and the expression of iNOS and COX-2 with lipopolysaccharide (TLR4 agonist) in murine macrophages. EEM suppressed NF-κB activation and iNOS and COX-2 expression induced by LPS. These results suggest that EEM may regulate TLR4 signalling pathways and this may be a useful strategy for anti-inflammatory therapies.     

亚低温治疗对脑出血大鼠TLR4/NF-κB介导的神经炎症反应的影响

目的:研究亚低温治疗对脑出血后大鼠Toll样受体4(toll-like receptor 4,TLR4)/核因子-κB(nuclear factor kappa B,NF-κB)介导的神经炎症反应的影响。方法:60只成年SD大鼠随机分为假手术组(Sham组)、脑出血模型组(ICH组)和亚低温治疗组(n=20)。采用自体血注入法复制大鼠脑出血模型,并给予亚低温干预。应用Berdson评分标准对各组大鼠进行神经功能评分,放射免疫法检测肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)、白介素1β(interleukin-1beta,IL-1β)的含量;免疫组织化学法及免疫印迹法检测TLR4、NF-κB的蛋白表达情况。结果:与Sham组比,模型组大鼠神经功能评分明显增加(P0.05),TNF-α和IL-1β的含量明显升高(P0.05),血肿周围脑组织TLR4和NF-κB的表达显著上调(P0.05)。与模型组相比,亚低温治疗组大鼠神经功能评分显著减少(P0.05),TNF-α和IL-1β的含量明显降低(P0.05),TLR4和NF-κB蛋白的表达量显著下调(P0.05)。结论:亚低温治疗能通过调控TLR4/NF-κB表达,减轻大鼠脑出血后血肿周围脑组织的炎症反应,具有一定的神经保护作用。