课程文献中心 更多>>

摘要： Vascular oxidative stress serves as a pathological foundation for various vascular injury-related diseases， including atherosclerosis， hypertension， restenosis， and abdominal aortic aneurysms. Recent studies have indicated that the intestinal flora-derived metabolites phenylacetylglutamine (PAGln) and phenylacetylglycine (PAGly) may contribute to the promotion of thrombosis， heart failure， and other related conditions. Aucubin (AU)， an iridoid glycoside， has been shown to exhibit anti-cardiovascular properties. Nevertheless， the precise role and underlying mechanisms by which AU mitigates PAGly-induced vascular injury remain poorly understood. Our results indicated that PAGln/PAGly promoted oxidative stress in vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vitro and in vivo. Network pharmacology suggest that AU may possess the capacity to regulate lipid and atherosclerosis， and reactive oxygen species (ROS) processes. We found that AU penetrated the blood vessels and mitigated oxidative stress induced by PAGln/PAGly. Mechanistically， combined the results from intersections analysis between the targets of AU and vascular diseases and molecular docking， we found that TNF may be the potential target of AU. Further DARTS and molecular docking analysis demonstrated that AU bound to recombinant TNF-α， and AU could interact with multiple amino acid residues of TNF-α including Asn-92 and Phe-144. Additionally， PAGly upregulated the level of soluble TNF-α (sTNF-α) in mouse VSMCs and plasma， and promoted the interaction between sTNF-α and TNF receptor 1 (TNFR1)， whereas AU inhibited this interaction. Both AU and Infliximab， a specific monoclonal antibody of TNF-α， inhibit TNF-α-induced ROS production. In summary， our results revealed that TNF-α is a cellular target of AU， and the interaction between AU and sTNF-α may mitigate PAGln/PAGly-induced vascular oxidative stress by inhibiting the interaction of TNF-α-TNFR1.

关键词： IL-8   DNA repair   genotoxicity   endotoxin   PM10   oxidative stress   waste treatment  

摘要： Biogas plants for sewage and organic waste treatment are rapidly expanding. While these facilities provide valuable benefits, such as renewable energy production and the promotion of circular economy practices, they also emit airborne particles of biological origin, which may pose potential health risks. This study aims to evaluate, by in vitro assay, the cytotoxic and genotoxic potential of PM10 sub-fractions (0.49-10 mu m and <0.49 m) generated in eight different plants, also assessing the endotoxin component using the Limulus Amebocyte Lysate (LAL) assay. Human embryonic lung fibroblasts (HELF) were exposed to organic extracts of particulate matter (PM). Cytotoxic effects (XTT assay) were analyzed, along with the modulation of gene expression involved in DNA repair (ERCC1, XRCC1, XPA, and XPF) and IL-8 production as a marker of inflammatory response. PM10 and endotoxin concentrations varied significantly among the plants (ANOVA, p < 0.01), with PM10 levels ranging from 14 to 18,000 g/m(3) and endotoxin content from 1 to 138 EU/m(3). Exposure significantly increased ERCC1 and IL-8 expression by 25% and 53%, respectively (paired t-test, p < 0.01). IL-8 expression correlated with endotoxin exposure (Spearman's rho = 0.35;p < 0.01). A deeper understanding of the biological component of airborne PM10 can enhance risk assessments for occupational and nearby resident communities' safety.

关键词： 白细胞介素-33   非瓣膜性心房颤动   可溶性基质裂解素2   预测价值  

摘要： 目的 探究白细胞介素-33(IL-33) mRNA及其受体可溶性基质裂解素2(sST2)mRNA在非瓣膜性心房颤动(NVAF)患者抗凝治疗后发生血栓中的预测价值。方法 选取2023年2月到2024年3月于九四〇医院接受诊治的340例NVAF患者为研究组，同期体检健康者100例作为对照组，按照随访期内发生终点事件情况（是否发生动脉血栓）将NVAF组分为血栓事件组(n=33例)以及无事件组(n=307例)两个亚组。采用RT-PCR测定受试者外周血中IL-33 mRNA、sST2 mRNA表达水平，并比较3组IL-33 mRNA、sST2 mRNA表达的差异，同时采用ROC曲线评价IL-33 mRNA、sST2 mRNA预测血栓事件的性能，采用Logistic多元回归分析得出优势比(OR)，采用Cox比例风险回归模型得出风险比(HR)。结果 与对照组比较，NVAF组及其两个亚组（血栓事件组和无事件组）IL-33 mRNA、sST2 mRNA表达明显升高(均P<0.01)；血栓事件组IL-33 mRNA、sST2 mRNAT表达较无事件组、NVAF组均明显升高(均P<0.01)。外周血IL-33 mRNA、sST2 mRNA预测NVAF患者3个月内血栓事件的AUC分别为0.823、0.802，而联合诊断的AUC为0.923，且灵每度为88.16%，特异度为85.58%，均高于单个指标；单因素分析结果显示，NVAF患者外周血IL-33 mRNA、sST2 mRNA与年龄、缺血事件、血管疾病、高血压、2型糖尿病和慢性心力衰竭等显著相关(均P<0.01)，而与性别、抗凝药物类型和服药依从性等则无显著相关，多元Logistic回归分析显示IL-33 mRNA、sST2 mRNA与缺血事件、血管疾病、高血压、2型糖尿病和慢性心力衰竭等显著相关(均P<0.01)，而与年龄则无显著相关。Cox回归模型结果显示，外周血IL-33 mRNA、sST2 mRNA表达未高于临界值者与高于临界值者在3个月内的血栓事件相对HR分别为0.773和0.801，而两者联合预测时，其血栓事件相对HR为0.734，可有效识别血栓事件。结论 NVAF抗凝患者外周血中IL-33 mRNA、sST2 mRNA表达变化与多种临床病理因素相关，并与3个月内的血栓风险关系紧密，对此类患者发生血栓的预测有指导作用。

关键词： 甲状腺癌   甲状腺髓样癌   流式细胞术   定量PCR法   新靶点  

摘要： 目的:探讨不同种类甲状腺癌患者体内IL-9来源细胞及分布特点。方法:选取2021年3月—2023年12月甲状腺乳头状癌22例和甲状腺髓样癌8例,以同期30例健康体检者为对照组,收集术前、后7天甲状腺癌患者及对照组血液标本,流式细胞术检测外周血单个核细胞(PBMC)中IL-9表达;酶联免疫吸附法测定外周血清中细胞因子IL-13、IL-4、IL-33、IL-25、IL-1β、IL-9、IL-21水平;荧光定量PCR测定血细胞PU. 1、SMAD2、TGF-β、STAT3m RNA水平。收集术中甲状腺癌组织及癌旁组织标本,荧光定量PCR法检测组织中IL-25、IL-33、IL-1β、IL-13、RORα及IL-9的m RNA表达水平,免疫荧光染色分析癌组织及癌旁组织中IL-9的表达状况。结果:流式细胞检测结果显示,产IL-9源的T细胞(Th9细胞)分布频率,甲状腺乳头状癌组明显高于甲状腺髓样癌组,且甲状腺髓样癌组高于对照组,经手术后甲状腺癌患者组均较术前显著上升;而产IL-9的二型固有淋巴细胞(ILC2细胞)在各组间分布无差异。甲状腺癌患者术前血清IL-9、IL-33、IL-25、IL-1β、IL-4、IL-21水平均显著高于对照组,术后血清IL-9、IL-4水平明显升高而IL-33、IL-25水平显著下降。定量PCR结果显示,对照组Th9相关调控因子PU. 1、SMAD2、TGF-β、STAT3的m RNA表达水平最低,且术后甲状腺癌患者组较术前表达显著升高。癌组织定量PCR检测结果表明,甲状腺髓样癌组织中IL-25、IL-33m RNA表达水平显著高于甲状腺乳头状癌,且甲状腺乳头状癌组织显著高于癌旁组织,而IL-9、IL-1βm RNA表达水平相反;组织免疫荧光染色结果证明,癌组织IL-9表达水平较癌旁组织显著降低,且IL-9主要存在于CD4+T细胞。结论:甲状腺癌患者体内参与抗肿瘤作用的IL-9主要来源于Th9且其分布可能与甲状腺癌的恶性程度相关,IL-9的检测有望成为甲状腺癌患者诊断和治疗新靶点。

关键词： MHC class II   Genetic diversity   Phylogroups   Pathogenic load   Natural selection   Population differentiation   Amplicon sequencing   Illumina  

摘要： The common hamster is listed in the IUCN Red Data Book as a species with a drastically decreasing population. At the same time, against the background of a general decline in nature, the species began to actively settle in cities. A consequence of the population decline is reduced genetic diversity, which in turn can lead to decreased resistance to pathogens, reproductive deterioration, etc. We analyzed the allelic diversity of exon 2 of the DRB gene in common hamsters belonging to phylogroups from the eastern part of the range ("Europe", "Caucasus", "Altai"), using amplicon sequencing on the Illumina platform. The results were compared to earlier known data from urban and rural populations in Crimea, and two populations from the western part of the range ("Pannonia", "North"). We found that the allelic diversity of the DRB gene in the eastern part of the range is three times greater than that of the western ones. Based on the number and diversity of alleles and corresponding amino acid sequences, the presence of unique alleles, the phylogroup "Europe" is the most diverse. The "Caucasus" is the least diverse of all the eastern populations. The urban Crimean population, belonging to "Europe", in contrast, exhibits the greatest diversity in alleles compared to all newly studied populations. Notably, positive selection for antigen-binding regions has only been shown for urban populations. This information can be used for conservation planning for common hamster.

关键词： tears   inflammation   microquantities volume   automated cell counter  

摘要： Background/Objectives: Tears are a promising source of biomarkers reflecting both ocular and systemic conditions. However, small sample volumes and low cell yields pose technical challenges in analytical workflows. This study aimed to evaluate the feasibility of quantifying total cell counts and characterizing HLA-DR and CD3 expression in tear-derived cells using an automated cell counter with fluorescence detection (Countess 3 FL). Methods: Tears were collected from 31 patients, centrifuged and the resulting pellet was incubated with HLA-DR and CD3 antibodies, markers of inflammation and T lymphocytes, respectively. Data obtained from Countess 3 FL were compared with conventional flow cytometry and immunofluorescence. For technical performance analysis, precision and reproducibility of cell count and staining were measured. For method validation, an in vitro model of hyperosmolar stress was assessed by culturing conjunctival epithelial cells (CCL20.2) with 350 or 450 mOsm NaCl. Results: The total cell yield in each tear sample correlated with the tear surnatant volume, in a range of 1-40 mu L (mean total cell number: 1.3 +/- 1.1 x 10(4), correlation analysis with tear volume: r = 0.47, p < 0.05). HLA-DR and CD3 were detected in all samples, with a mean value, respectively, of 43.6% (+/- 21.0) and 25.0% (+/- 15.0) intensity. Data were comparable to those obtained from standard flow cytometry ***-DR increase in CCL20.2 exposed to hyperosmolar stress was recorded using Countess 3FL reading, confirming the detection capacity of the proposed method. Conclusions: The automated cell counter can provide HLA-DR and CD3 quantification in tear cell samples, despite the high variability and the low volume availability of tear samples. Method standardization and technical improvements are necessary to strengthen this application in the clinical setting.

关键词： cardiovascular disease   dupilumab   eczema   malignancy   tofacitinib   upadacitinib  

关键词： 结核分枝杆菌   Rv1767基因   pMV261   炎性应答   细胞凋亡  

摘要： 为探究结核分枝杆菌Rv1767基因的功能，将重组菌株Ms-pMV261-Rv1767滴鼻感染小鼠，在感染后1，4，7，14，21，28 d对小鼠进行组织（肺、脾）和血清采样，检测肺部的细菌载量以及炎症相关细胞因子的表达量，并对肺部病理切片以及TUNEL染色结果进行分析。结果表明：Rv1767增强了重组菌株在小鼠肺脏的定殖能力，增强了小鼠肺脏的病理损伤，抑制了小鼠炎性细胞因子的分泌以及肺脏的细胞凋亡，提示Rv1767可能是结核分枝杆菌的重要致病因素。