MHC Class I Immunopeptidome: Past,Present, and Future

In the 35 years since the revelation that short peptides bound to major histocompatibility complex class I and II molecules are the secret of the major histocompatibility complex–restricted nature of T-cell recognition, there has been enormous progress in characterizing the immunopeptidome, the repertoire of peptide presented for immunosurveillance. Here, the major milestones in the journey are marked, the contribution of proteasome-mediated splicing to the immunopeptidome is discussed, and exciting recent findings relating the immunopeptidome to the translatome revealed by ribosome profiling (RiboSeq) is detailed. Finally, what is needed for continued progress is opined about, which includes the infusion of talented young scientists into the antigen-processing field, currently undergoing a renaissance; thanks in part to the astounding success of T-cell–based cancer immunotherapy.     

Integrated computational approaches to screen gene expression data to determine key genes and therapeutic targets for type-2 diabetes mellitus

There is a rapid rise in cases of Type-2-diabetes mellitus (T2DM) globally, irrespective of the geography, ethnicity or any other variable factors. The molecular mechanisms that could cause the condition of T2DM need to be more thoroughly analysed to understand the clinical manifestations and to derive better therapeutic regimes. Tools in bioinformatics are used to trace out key gene elements and to identify the key causative gene elements and their possible therapeutic agents. Microarray datasets were retrieved from the Gene expression omnibus database and studied using R to derive different expressed gene (DEG) elements. With the comparison of the expressed genes with disease specific genes in DisGeNET, the final annotated genes were taken for analysis. Gene Ontology studies, Protein–protein interaction (PPI), Co-expression analysis, Gene-drug interactions were performed to scale down the hub genes and to identify the novelty across the genes analysed so far. In vivo and invitro analysis of key genes and the trace of interaction pathway is crucial to better understand the unique outcomes from the novel genes, forming the basis to understand the pathway that ends up causing T2DM. Afterwards, docking was executed enabling recognition of interacting residues involved in inhibition. The complex CCL5-265 and CD8A-40585 thus docked showed best results as is evident from its PCA analysis and MMGBSA calculation. There is now scope for deriving candidate drugs that could possibly detect personalized therapies for T2DM.     

全球啄木鸟濒危格局及研究现状

啄木鸟科物种作为初级洞巢者与蛀干害虫控制者,对森林高度依赖,是森林生态系统重要的伞护种和环境指示物种。自20世纪以来,由于全球范围的栖息地丧失和片段化,啄木鸟科物种的森林生境急剧萎缩,威胁着该类群物种的生存和繁衍。为探究啄木鸟科动物濒危情况和研究现状,本研究利用世界自然保护联盟濒危物种红色名录(IUCN Red List)和国际鸟盟(BirdLife International)在线数据库,检索并整理出1988年到2023年以下内容：(1)全球啄木鸟的物种数、濒危等级及其变化情况;(2)各大洲的啄木鸟物种数及其受威胁物种的比例;(3)啄木鸟的主要威胁因素;(4)通过Google学术搜索等方式检索并统计啄木鸟相关文章的研究内容。结果显示：(1)目前现存254种啄木鸟,33年间全球受威胁啄木鸟由7种增加至18种,受威胁物种数占当年已命名啄木鸟物种数的比例由3.4%上升至7.0%。(2)亚洲、南美洲和北美洲各分布了83种、93种和56种啄木鸟,受威胁物种占比分别为12.0%、6.4%、5.3%。非洲和欧洲分别分布了36种和11种啄木鸟,当前没有受威胁物种。(3)农业和生物资源利用以及放牧是啄木鸟的主要威胁因素。(4)共检索到研究啄木鸟的有关文章1 024篇,研究覆盖了140种啄木鸟,其中,文章数最多的物种是红顶啄木鸟(Leuconotopicus borealis)(162篇)。研究主要集中在巢相关特征(129篇)、生境选择特征(122篇)、取食行为(112篇)、繁殖行为(99篇)和种群状况(66篇)等基础生态学内容。这些研究为啄木鸟生物学、生态学积累了一定的基础,但物种覆盖程度还远远不够。在生物多样性急剧丧失的大背景下,亟需开展更为广泛和深入的研究。本研究对全球啄木鸟的濒危格局与研究现状进行了全面的分析,以期为后续啄木鸟的研究与保护工作提供参考。     

The role of monocyte/macrophages as vehicles of dissemination of Simkania negevensis: an in vitro simulation model

Exposure to Simkania negevensis (Sn), an intracellular microorganism that has been associated with respiratory tract infections in infants and adults, is prevalent. Sn can multiply within free-living amoebae and has been detected in domestic water supplies, which may constitute a source of infection with the organism. Its path of transport from its portal of entry to the body to its target organs is unknown. In this study, the possibility that monocytes/macrophages may serve as vehicles of transmission was examined. In vitro cocultivation of Sn-infected Acanthamoeba polyphaga with the monocyte/macrophage cell line U937 resulted in the death of the amoebae and infection of the U937 cells. Sn entered and multiplied in U937 cells within short periods of time, and the microorganism could be transferred from U937 cells to cell cultures of various origins. Uninfected monocyte/macrophages could become infected when in contact with either actively or persistently Sn-infected cell cultures. Persistently infected cultures in contact with uninfected U937 cells became actively infected. The results of this study provide a basis for determination of the molecular mechanisms of monocyte/macrophage-cell interactions in transfer of infection and may contribute to a better understanding of the pathogenesis of Sn infections in vivo.     

Molecular genetic characterization of H5N1 influenza virus strains isolated from poultry in the Kurgan region in 2005

In the second half of 2005, a large-scale outbreak of influenza in poultry and wild birds was caused by a highly pathogenic H5N1 influenza virus in Russia. The level of pathogenicity is a polygenic trait, and most individual genes contribute to the influenza A virus pathogenicity in birds, animals, and humans. The full-length nucleotide sequences were determined for H5N1 strains isolated in the Kurgan region (Western Siberia). The structure of viral proteins was analyzed using the deduced amino acid sequences. The receptor-binding site of hemagglutinin (HA) in strains A/chicken/Kurgan/05/2005 and A/duck/Kurgan/08/2005 was typical for avian influenza viruses and contained Glu and Gly at positions 226 and 228, respectively. The structure of the basic amino acid cluster located within the HA cleavage site was identical in all isolates: QGERRRKKR. According to the neuraminidase structure, all H5N1 isolates from the Kurgan region were assigned to the Z genotype. Amino acid residues typical for the avian influenza virus were revealed in 30 out of 32 positions of M1, M2, NP, PA, and PB2, determining the host range specificity. One of the strains contained Lys at position 627 of PB2. Isolates from the Kurgan region were shown to have a remantadine-sensitive genotype. Both strains contained Glu at position 92 of NS1, indicating that the virus is interferon-resistant. Phylogenetic analysis related the Kurgan isolates to subclade 2 of clade 2 of highly pathogenic H5N1 influenza viruses.     

原发性肝癌患者术后癌因性疲乏的影响因素及其预测模型构建

摘要 目的：分析原发性肝癌患者术后癌因性疲乏（CRF）的影响因素并构建预测模型。方法：选取2020年1月～2023年1月湖南师范大学附属第一医院收治接受手术治疗的200例原发性肝癌患者,根据术后3个月是否存在CRF将患者分为CRF组（124例）和非CRF组（76例）。单因素和多因素Logistic回归分析影响原发性肝癌患者术后CRF的因素并构建其预测模型。通过受试者工作特征（ROC）曲线分析预测模型对原发性肝癌患者术后CRF的预测价值。结果：单因素分析显示,CRF组病程长于非CRF组,Child-Pugh分级B级、美国东部肿瘤协作组功能状态（ECOG）评分1～2分、辅助化疗、医疗付费方式自费、抑郁/焦虑比例高于非CRF组,文化程度高中及以上、家庭月收入＞3000元、高度社会支持度比例低于非CRF组（P＜0.05）。多因素Logistic回归分析显示,病程延长、Child-Pugh分级B级、ECOG评分1～2分、辅助化疗、医疗付费方式自费、抑郁/焦虑为影响原发性肝癌患者术后CRF的独立危险因素,家庭月收入＞3000元、高度社会支持为独立保护因素（P＜0.05）。原发性肝癌患者术后CRF的预测模型方程：Logit（P）=P/1-P=-1.252+0.409×病程+0.839×Child-Pugh分级+1.378×ECOG评分+1.055×辅助化疗+1.476×医疗付费方式-0.793×家庭月收入+0.883×抑郁/焦虑-1.260×社会支持度。霍斯默-莱梅肖检验P＞0.05。ROC曲线分析显示,模型预测原发性肝癌患者术后CRF的曲线下面积为0.910,敏感度为87.10%,特异度为85.53%。结论：病程、Child-Pugh分级、ECOG评分、辅助化疗、医疗付费方式、抑郁/焦虑、家庭月收入、社会支持度为影响原发性肝癌患者术后CRF的因素,基于此构建的预测模型对原发性肝癌患者术后CRF的预测价值较高,可能有助于临床早期发现和干预原发性肝癌患者术后CRF,以改善患者预后。     

健脾益肾活血方联合达格列净对糖尿病肾病患者炎症因子、氧化应激和血清AGEs、NGAL、MCP-1的影响

摘要 目的：观察健脾益肾活血方联合达格列净对糖尿病肾病（DN）患者炎症因子、氧化应激和血清中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、晚期糖基化终末产物（AGEs）、单核细胞趋化蛋白1（MCP-1）的影响。方法：根据随机数字表法将如皋市中医院2021年6月~2023年3月期间收治的120例DN患者分为对照组（60例,常规治疗基础上接受达格列净治疗）和研究组（60例,对照组基础上接受健脾益肾活血方治疗）。对比两组疗效、炎症因子[白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）]、肾功能[血肌酐（Scr）、血尿素氮（BUN）、尿微量白蛋白/肌酐比值（UACR）]、氧化应激[丙二醛（MDA）、超氧化物歧化酶（SOD）]和血清AGEs、NGAL、MCP-1水平,同时观察两组治疗期间不良反应发生情况。结果：研究组的临床总有效率高于对照组（P<0.05）。两组治疗2个疗程后Scr、BUN、UACR下降,且研究组低于对照组（P<0.05）。两组治疗2个疗程后CRP、TNF-α、IL-1β下降,且研究组低于对照组（P<0.05）。两组治疗2个疗程后MDA下降,且研究组低于对照组;SOD升高,且研究组高于对照组（P<0.05）。两组治疗2个疗程后NGAL、AGEs、MCP-1下降,且研究组低于对照组（P<0.05）。两组不良反应发生率对比未见差异（P>0.05）。结论：健脾益肾活血方联合达格列净可有效减轻DN患者氧化应激和炎症反应,调节血清AGEs、NGAL、MCP-1水平。     

miR-455-5p靶向SOCS3抑制RSV感染致气道上皮炎症反应的机制研究

摘要 目的：揭示miR-455-5p对呼吸道合胞病毒（RSV）感染致气道上皮细胞炎症反应的作用机制。方法：qRT-PCR检测30例健康体检儿童（健康组）、RSV感染轻症组（n=41）和重症组（n=31）患儿血清miR-455-5p水平。将16HBE细胞分为Control组、NC-agomir组、miR-455-5p-agomir组、NC-antagomir组、miR-455-5p-antagomir组。使用Lipofectamine 3000转染16HBE细胞后培养48 h后,分为Blank组、NC组（转染了NC-agomir的细胞）、RSV+NC-agomir组、RSV+miR-455-5p-agomir组,用RSV病毒液感染RSV+NC-agomir组和RSV+miR-455-5p-agomir组16HBE细胞,Blank组和NC组16HBE细胞正常培养。用CCK-8法和EdU法检测细胞增殖、TUNEL法检测细胞凋亡、ELISA法检测上清液中TNF-α、IL-6、IL-8水平,qRT-PCR检测miR-455-5p和SOCS3的mRNA水平,Western blot检测SOCS3、IFN-α、STAT1、STAT2、p-STAT1和p-STAT2的蛋白水平。结果：与健康组相比,轻症组和重症组患儿的血清miR-455-5p水平降低（P<0.05）。与轻症组相比,重症组的血清miR-455-5p水平降低（P<0.05）。与Control组和NC-agomir组相比,miR-455-5p-agomir组16HBE细胞的miR-455-5p水平、相对细胞活力和EdU阳性率升高（P<0.05）,TUNEL阳性率降低（P<0.05）,上清液中的TNF-α、IL-6和IL-8水平降低（P<0.05）,SOCS3 mRNA和蛋白水平降低（P<0.05）,IFN-α蛋白、STAT1和STAT2磷酸化水平升高（P<0.05）。与Control组和NC-antagomir组相比,miR-455-5p-antagomir组16HBE细胞的miR-455-5p水平、相对细胞活力和EdU阳性率降低（P<0.05）,TUNEL阳性率升高（P<0.05）,上清液中的TNF-α、IL-6和IL-8水平升高（P<0.05）,SOCS3 mRNA和蛋白水平升高（P<0.05）,IFN-α蛋白、STAT1和STAT2磷酸化水平降低（P<0.05）。与Blank组和NC组相比,RSV+NC-agomir组16HBE细胞的miR-455-5p水平、相对细胞活力和EdU阳性率降低（P<0.05）,TUNEL阳性率升高（P<0.05）,上清液中的TNF-α、IL-6和IL-8水平升高（P<0.05）,SOCS3 mRNA和蛋白水平升高（P<0.05）,IFN-α蛋白、STAT1和STAT2磷酸化水平降低（P<0.05）。与RSV+NC-agomir组相比,RSV+miR-455-5p-agomir组的miR-455-5p水平、相对细胞活力和EdU阳性率升高（P<0.05）,TUNEL阳性率降低（P<0.05）,上清液中的TNF-α、IL-6和IL-8水平降低（P<0.05）,SOCS3 mRNA和蛋白水平降低（P<0.05）,IFN-α蛋白、STAT1和STAT2磷酸化水平升高（P<0.05）。结论：miR-455-5p在RSV感染患儿血清中下调,上调miR-455-5p通过抑制SOCS3的转录和表达从而激活RSV感染的16HBE细胞中IFN-α介导的抗病毒反应。