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关键词： Psoriasis   IL-17A inhibitor   16S rDNA gene   Skin microbiome stability  

摘要： BackgroundThe IL-17A inhibitors target aberrant immune responses in psoriasis but also impacts the host's defense against infections. The effects of this treatment on skin microorganisms and microbiome-encoded metabolic pathways remain *** was an exploratory clinical study designed to investigate whether Psoriasis is associated with skin microbiota, as well as a longitudinal cohort study aimed at revealing the effects of IL-17A inhibitor treatment on skin microbiota in *** this study, we recruited 26 patients with moderate to severe psoriasis and 15 healthy controls. We collected skin microbiome samples from both greasy and dry skin regions. All samples were analyzed using 16S rDNA gene sequencing to determine the microbial *** with healthy controls, the composition and function of skin microbiome in psoriasis patients are heterogeneous. Treatment with IL-17A inhibitors significantly increases the alpha diversity of the skin microbiota in psoriasis patients, indicating potential restoration of microbial community richness and evenness. However, this treatment does not entirely alter the taxonomic composition of the skin microbiota;rather, it shifts the relative abundance of specific microbial species, indicating that certain core microbial features remain relatively stable. Moreover, IL-17A inhibitors help adjust the functional profile of the skin microbiome in psoriasis patients, bringing it closer to that of healthy *** patients exhibit significant heterogeneity in both the composition and functionality of their skin microbiota. Although IL-17A inhibitor treatment fails to fundamentally alter its taxonomic composition, this therapy effectively enhances microbial community stability by increasing alpha diversity and modulating the relative abundance of various taxa. Additionally, it adjusts the functional profile of the skin microbiota towards a healthier state, thereby contributin

关键词： Acetaminophen   Oxidative stress   Antioxidant   Inflammation   Lagerstroemia Speciosa   NAPQI  

摘要： Acetaminophen (APAP) is a widely used analgesic and antipyretic, but its toxicity can lead to liver injury or failure. This study evaluated the hepatoprotective mechanisms of L. speciosa ethanolic leaf extract (LSE) against APAP-induced hepatic damage. Rats were randomly divided into five groups: Control (Cont), APAP (2 g/kg b.w. single oral dose on day 22), LSE (500 mg/kg b.w./day), APAP + LSE, and APAP + NAC (initial NAC dose of 100 mg/kg b.w. two hours post-APAP, followed by maintenance doses every 12 h). APAP-intoxicated rats showed leukocytosis, decreased erythrocyte count, Hb, and PCV, increased serum bilirubin, and elevated ALT, AST, and ALP activities. APAP intoxication also decreased plasma protein levels, albumin, and globulin while increasing liver MDA and depleting GSH. The expressions of hepatic SOD and CAT were reduced, while NF-kappa B, TNF-alpha, iNOS, Nrf2, and HO-1 were significantly upregulated. Also, APAP increased Bax and decreased Bcl-2. LSE improved most parameters, suppressing oxidative stress, inflammation, and apoptosis and regulating NF-kappa B, TNF-alpha, iNOS, Nrf2, HO-1, Bax, and Bcl-2 expression. Nevertheless, the deeper upstream molecular targets of LSE require further exploration. Its effects were comparable to NAC, with NAC showing slightly superior outcomes in some markers. Our findings suggest that LSE contains hepatoprotective phytochemicals capable of mitigating oxidative damage, inflammation, and apoptosis induced by APAP, supporting its potential as a natural alternative for managing drug-induced liver injury.

摘要： Regulatory T cell (Treg) therapy is an emerging platform for controlling immune overactivation. Efficacy of Treg therapy is limited by the poor persistence of infused Tregs due to insufficient IL-2, which is essential for Treg survival and function. IL-2 activates many immune cells besides Tregs, imposing a challenge for the selective provision of IL-2 to infused Tregs. In this study, we found infusions of orthogonal (ortho) IL-2 failed to enhance Tregs engineered with a corresponding orthoIL-2 receptor (IL-2R) in a mouse model of autoimmune diabetes. We then developed a receptor-tethered orthoIL-2 by optimizing the combination of IL-2, IL-2R, and the linker connecting them to achieve autocrine signaling selectively in engineered Tregs. Tregs expressing the tethered orthoIL-2 showed autocrine IL-2 signaling in vitro, enhanced CD25, CTLA-4, and Foxp3 expression, persisted without exogenous IL-2 in vivo, and prevented autoimmune diabetes using as few as 2,000 Tregs. Knocking the tethered orthoIL-2 construct into the Foxp3 locus enabled Treg-specific expression, with the additional benefit of positively reinforcing tethered orthoIL-2 expression through the activation of the Foxp3 gene by enhanced IL-2 signaling. Together, these results illustrate a safe and effective cell-engineering solution for overcoming Tregs' dependency on exogenous IL-2, thereby achieving superior therapeutic efficacy.

关键词： 类风湿性关节炎   细胞因子-细胞因子受体相互作用通路   机器学习   无监督聚类分析  

摘要： 背景：类风湿性关节炎是一种自身免疫性疾病，受发病机制和患者个体体质差异影响，患者治疗效果存在显著不同，部分患者因对治疗药物不敏感，发展为难治性类风湿性关节炎。因此寻找类风湿性关节炎的特征基因、挖掘新的治疗靶点，已成为该领域亟待解决的关键问题。目的：运用生物信息学分析方法，探究细胞因子-细胞因子受体相互作用通路相关基因在类风湿性关节炎诊断、分型及功能解析中的作用。方法：从基因表达综合数据库(GEO,https://***/geo/，由美国国立生物技术信息中心创建并维护的基因表达数据库)下载4个包含类风湿性关节炎样本的数据集，各数据集均为公开发表的数据，符合伦理学要求。将GSE55235、GSE55457和GSE77298数据集合并作为训练集，GSE12021数据集作为验证集。研究流程：(1)分析细胞因子-细胞因子受体相互作用通路在类风湿性关节炎中的失调状态，筛选该通路相关的差异表达基因；(2)综合采用随机森林算法、最小绝对收缩和选择算子、支持向量机-递归特征消除法、Boruta全特征选择算法及加权基因共表达网络分析，进一步筛选类风湿性关节炎中与细胞因子-细胞因子受体相互作用通路相关的特征基因；(3)基于筛选出的差异基因，运用无监督聚类分析方法，将类风湿性关节炎划分为不同的分子亚型，并对比分析各亚型间信号通路活性及免疫细胞浸润水平的差异；(4)通过构建类风湿性关节炎细胞模型，对特征基因的表达水平进行实验验证。结果与结论：(1)经多方法整合分析，成功筛选出3个特征基因；(2)基于细胞因子-细胞因子受体相互作用通路可将类风湿性关节炎分为2种亚型：甲氨蝶呤敏感型和不敏感型，根据此分型可以指导类风湿性关节炎的临床治疗，避免盲目使用甲氨蝶呤，及时调整治疗策略，选择更有效的药物或治疗组合，从而提高治疗效果，改善患者的病情，提升类风湿性关节炎治疗的有效性和精准性。

关键词： atopic dermatitis   interleukins   dupilumab   interleukin 4   interleukin 13   interleukin 10  

摘要： Background Interleukins IL-4, Il-5, IL-10, IL-13 and IL-33 play an important role in atopic dermatitis patients. The aim of our study is to address several knowledge gaps in the understanding of interleukin dynamics in atopic dermatitis patients and the effects of dupilumab *** We conducted an assessment of plasma levels of interleukins IL-4, IL-5, IL-10, IL-13 and IL-33 in 89 AD patients and in 44 healthy individuals as a control group. The group of AD patients consisted of 27 patients treated with dupilumab (15 men, 12 women) at a mean age of 44.8 years and 62 patients without dupilumab treatment (35 women and 27 men) at a mean age of 46.3 years. The control group consisted of 44 healthy subjects (22 men, 22 women), at a mean age of 43.3 years. Patients were treated with a standard dose of dupilumab, 300 mg s.c. every two weeks. For screening analysis of plasma levels of selected cytokines, the performance assay Human cytokine Luminex was used. Blood samples were unstimulated and stimulated with phorbol myristate acetate and ionomycin. This stimulation provides non-specific stimulation of innate and adaptive immunity cells and increases their cytokine production. The level of interleukins IL-4, IL-5, IL-10, IL-13 and IL-33 were compared in AD patients with the results in control group. Nonparametric Kruskal-Wallis analysis of variance with post-hoc Dunn's test with Bonferroni modification of significance level was *** The significantly higher plasma level of stimulated IL-5 was confirmed in AD patients treated with dupilumab and significantly higher plasma IL-10 levels were confirmed in both dupilumab and non-dupilumab treated patients compared to control group. Stimulated IL-4 levels are significantly higher in patients treated with dupilumab compared to patients without dupilumab. The significant difference in IL-13 and IL-33 in AD patients compared to control group was not *** By identifying significant differences in IL-5

关键词： 犬瘟热病毒   N蛋白   原核表达   单克隆抗体  

摘要： 为制备犬瘟热病毒（CDV）N蛋白的特异性单克隆抗体，本研究采用原核表达系统构建重组表达质粒，经诱导表达并纯化后，所得蛋白用于免疫BALB/c雌性小鼠。通过细胞融合、筛选及亚克隆技术，成功获得一株交瘤细胞株（3D4），该细胞株能够稳定分泌抗CDV N蛋白单克隆抗体。该株抗体亚型鉴定为IgG1，轻链类型为κ链，腹水效价可达1：2048000。免疫荧光检测（IFA）和Western blot结果显示，该单克隆抗体可特异性与CDV毒株结合。本研究成功制备了针对CDV N蛋白的高效特异性单克隆抗体，为CDV的快速检测方法的建立与相关基础研究奠定了物质基础。

摘要： T cell receptors (TCRs) recognize peptides presented by polymorphic human leukocyte antigen (HLA) molecules, but HLA genotype data are often missing from TCR repertoire sequencing studies. To address this, we developed TCR2HLA, an open-source tool that infers HLA genotypes from TCRβ repertoires. Expanding on work linking public TRBV-CDR3 sequences to HLA genotypes, we incorporated "quasi-public" metaclonotypes - composed of rarer TCRβ sequences with shared amino acid features - enriched by HLA genotypes. Using four TCRβseq datasets from 3,150 individuals, we applied TRBV gene partitioning and locality-sensitive hashing to identify ∼96,000 TCRβ features strongly associated with specific HLA alleles from 71M input TCRs. Binary HLA classifiers built with these features achieved high balanced accuracy (>0.9) across common HLA-A (9/12), B (9/12), C (6/13), DRB1 (11/11) alleles and prevalent DPA1/DPB1 (6/10), DQA1/DQB1 (8/17) heterodimers. We also introduced a high-sensitivity calibration to support predictions in samples with as few as 5,000 unique clonotypes. Calibrated predictions with confidence filtering improved reliability. Beyond genotype imputation, TCR2HLA enables the discovery of novel HLA- and exposure-associated TCRs, as shown by the identification of SARS-CoV-2 related TCRs in a large COVID-19 dataset lacking HLA data. TCR2HLA provides a scalable framework for bridging the gap between TCRseq data and HLA genotype for biomarker discovery.