课程文献中心 更多>>

关键词： italic>Chlamydia muridarum   pGP3   IL-22   gastrointestinal tract   colonization  

摘要： Chlamydia trachomatis is the most important infectious cause of tubal infertility and is frequently detected in the human gastrointestinal tract. Chlamydia muridarum, a murine pathogen, closely resembles the human pathogen C. trachomatis. Our previous studies showed that the pGP3-deficient C. muridarum mutant was restricted to the large intestine following intracolonic inoculation, suggesting that the pGP3-deficient mutant was killed by the tissue beyond the large intestine. Here, we report that the intra-ilenum, but not the intra-jejunum, to bypass the gastric barrier rescued the colonization of pGP3-deficient C. muridarum, suggesting that pGP3 is required to overcome host factors of the jejunum to help C. muridarum reach the colon. Moreover, mice genetically deficient in IL-22 not only rescued the colonization of pGP3-deficient C. muridarum following intrajejunal inoculation but also rescued the colonization of pGP3-deficient C. muridarum in the whole gastrointestinal tract tissues following intracolonic inoculation on day 14, suggesting a critical role of IL-22 in regulating chlamydial spread. Importantly, IL-22RA1 flox/flox and Villin-cre mice rescued the colonization of pGP3-deficient C. muridarum following intrajejunal inoculation, suggesting that intestinal epithelial-specific IL-22RA1 signaling is important for the spread of pGP3-deficient C. muridarum from the small intestine to the large intestine. These observations provide a platform for further research on intestinal IL-22RA1 signaling in regulating bacterial spread in the intestine. Therefore, host factors identified in the gastrointestinal tract may also contribute to the female lower genital tract barrier during sexually transmitted diseases.

关键词： OSCC   PPAR gamma   TME   Th17 cells   IL-17   CEBPA  

摘要： BackgroundOral squamous cell carcinoma (OSCC) is a marked invasive epithelial tumor with limited treatment efficacy, especially in advanced stages. The immunosuppressive nature of the tumor microenvironment (TME) is a major contributor to OSCC development and therapeutic resistance. Peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to influence tumor biology in a multifaceted and context-specific manner. The objective of this research was to explore the role of PPAR gamma in modulating the TME and its impact on OSCC *** 4NQO-induced OSCC model was used to verify PPAR gamma overexpression by Immunohistochemistry (IHC). Bulk RNA-seq and single-cell RNA-seq analyses were employed to dissect PPAR gamma-driven tumor-promoting mechanisms. Co-cultivation of OSCC cells and CD4 + T cells in vitro, combined with subcutaneous tumor model in vivo, was employed to investigate the influence of PPAR gamma on Th17 cells *** of PPAR gamma significantly suppressed OSCC cell growth and downregulated IL-17 pathway-related genes, including IL-17C. PPAR gamma promoted Th17 cells differentiation via transcriptional upregulation of CEBPA/IL-17C/IL-17A signaling pathway. Evidence from cell-based and animal experiments confirmed that GW9662 treatment impaired Th17 cells polarization and reduced expression of CEBPA, IL-17C, and *** study identifies a novel PPAR gamma/CEBPA/IL-17C/IL-17A signaling axis that promotes Th17 differentiation and contributes to tumor-associated inflammation in OSCC. Targeting PPAR gamma represents a promising strategy to inhibit tumor progression and modulate the immune microenvironment, providing new insight into immunotherapeutic approaches for OSCC.

关键词： Inflammation   interleukin-1 beta   interleukin-6   symptomatology   schizophrenia  

摘要： ObjectiveThis study aimed to compare interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and inflammatory markers from the complete blood count in drug-free male schizophrenia (SCZ) patients during acute exacerbation with healthy controls and to evaluate changes after ***-one drug-free male SCZ patients hospitalised in an inpatient clinic and 61 healthy controls were included. Sociodemographic data, body measurements, and some scale scores were collected. Blood samples were drawn after 10-12 h of fasting to measure inflammatory parameters in patients (pre- and post-treatment) and *** to the control group, patients exhibited significantly higher neutrophil counts (5.13 vs. 4.51 x 10(3)/mu L), neutrophil-to-lymphocyte ratio (2.43 vs. 1.85), C-reactive protein (CRP) (3.18 vs. 1.63 mg/L), and erythrocyte sedimentation rate (ESR) (5.57 vs. 3.20 mm/hr), while eosinophil levels (0.17 vs. 0.25 x 10(3)/mu L) were significantly lower. Logistic regression indicated that eosinophil, CRP, and ESR predicted SCZ diagnosis. In the post-treatment period, IL-1 beta (2.65 to 1.61 ng/L) and IL-6 levels (1.42 to 0.92 ng/L) were significantly lower, while eosinophil levels (0.17 to 0.29 x 10(3)/mu L) were significantly higher compared to the pre-treatment *** in IL-1 beta and IL-6 after antipsychotic treatment support inflammatory processes in SCZ. Eosinophil, CRP, and ESR may serve as peripheral biomarkers .

关键词： superdonor   HLA class I   immune compatibility   hypoimmunogenic   population genetics  

摘要： Human-induced pluripotent stem cells with broad immune compatibility are highly desirable for regenerative medicine applications. Human leukocyte antigen (HLA) class I homozygous cell sources are ideal for immune compatibility modeling. Here, we profile HLA-A, HLA-B, and HLA-C alleles in 3,496 Lithuanian donors genotyped at three-field resolution. The five most frequent alleles constitute 74.6% of HLA-A, 43.2% of HLA-B, and 59.2% of HLA-C, with HLA-A*02:01:01, HLA-B*07:02:01, and HLA-C*07:02:01 being the most common. Lithuanian allele frequencies closely resemble those of European-American and British populations. We identified 153 double homozygotes and 51 triple homozygotes for HLA-A, HLA-B, and HLA-C. Compatibility modeling showed that triple homozygous profiles match 60.5% of Lithuanians, 13.4% of the British population, and 7.4% of European-Americans. CRISPR-Cas9 guide RNA design yielded 54 candidates predicted to disrupt HLA-A or HLA-B while preserving HLA-C, producing edited profiles matching over 97.9% of Lithuanians, 95.7% of European-Americans, and 95.5% of the British population. Finally, we established 15 fibroblast lines from triple homozygotes as a bioresource for the derivation of human-induced pluripotent stem cells and immune compatibility studies.

摘要： Interleukin 7 (IL-7) is an immunostimulatory cytokine essential for T cell development, proliferation, and maintenance. While IL-7 generates antitumor immunity, systemic IL-7 has not consistently produced strong anticancer effects. Achieving therapeutic cytokine concentrations in tumors often requires high systemic doses, leading to toxicity. To address this, localized cytokine expression within the tumor microenvironment (TME) has gained interest. One such approach involves cytokine expression by oncolytic viruses (OVs) that selectively replicate in cancerous cells while sparing 'normal' cells. Additionally, non-replicative viral vectors have become valuable tools for sustaining cytokine expression in the TME, inducing antitumor effects through non-lytic mechanisms. To effectively harness IL-7's antitumor potential, both oncolytic and non-lytic viruses have been engineered to express IL-7, either alone or in combination with other immunomodulators, such as IL-12, IL-15, B7-1, or CCL19. Despite promising advancements, no comprehensive review exists on IL-7 expression in virus-based immunotherapy for cancer. Therefore, this manuscript aims to (i) summarize studies on viral IL-7 expression alone or with other immunomodulators, (ii) discuss the associated immune mechanisms of action, and (iii) explore opportunities for co-expressing IL-7 with other key cytokines to optimize immunovirotherapy strategies for cancer.

关键词： 传染性支气管炎病毒   分离   鉴定   S1基因  

摘要： 为掌握河南省鸡群中传染性支气管炎病毒（IBV）的流行动态，本研究于2022年从河南省某疑似IBV感染的肉鸡场中采集气管、肺脏以及肾脏等病料组织，通过病毒分离、RT-PCR鉴定等分离获得1株IBV毒株，命名为HN-2022。采用Reed-Muench法测定该毒株的鸡胚半数感染量（EID50）为107.25/0.2 mL；基于S1基因的序列分析显示，HN-2022分离株与参考毒株H120、H52、M41、QX、4/91及LDT3的核苷酸同源性分别为76.8%、76.7%、77.3%、84.5%、86.4%及80.7%，氨基酸同源性分别为75.5%、75.3%、75.1%、84.9%、84.3%及78.3%；其中与W118株同源性最高（核苷酸94.2%，氨基酸92.2%）。系统发育分析表明，HN-2022株与W118株、4/91型、UK7/93及Chicken/JS/YZ07/2008分离株位于同一进化分支。HN-2022株与W118株、4/91型IBV、UK7/93及Chicken/JS/YZ07/2008 IBV分离株位于同一小分支；进一步对S1蛋白的理化性质和B 细胞抗原表位预测分析显示，其抗原表位与W118株的B细胞抗原表位一致性更高，仅在74-87与123-150氨基酸区域存在差异。本研究不仅丰富了本实验室病毒库资源，也为河南省IBV的防控策略制定提供了重要参考依据。

关键词： HLA   HLA-DRB1*11:351   novel allele   sequencing-based typing  

摘要： HLA-DRB1*11:351 differs from HLA-DRB1*11:04:01:01 by one nucleotide substitution in codon 229 in exon 5.

关键词： Cell stress   Endothelial cells   Inflammation   Innate immunity   Vascular biology  

摘要： Severe systemic inflammatory reactions, including sepsis, often lead to shock, organ failure and death, in part through an acute release of cytokines that promote vascular dysfunction. However, little is known about the vascular endothelial signaling pathways regulating the transcriptional profile in failing organs. This work focuses on signaling downstream of IL-6, due to its clinical importance as a biomarker for disease severity and predictor of mortality. Here, we show that loss of endothelial expression of the IL-6 pathway inhibitor, SOCS3, promoted a type I interferon (IFNI)-like gene signature in response to endotoxemia in mouse kidneys and brains. In cultured primary human endothelial cells, IL-6 induced a transient IFNI-like gene expression in a non-canonical, interferon-independent fashion. We further show that STAT3, which we had previously shown to control IL-6-driven endothelial barrier function, was dispensable for this activity. Instead, IL-6 promoted a transient increase in cytosolic mitochondrial DNA and required STAT1, cGAS, STING, and the IRFs 1, 3, and 4. Inhibition of this pathway in endothelial-specific STING knockout mice or global STAT1 knockout mice led to reduced severity of an acute endotoxemic challenge and prevented the endotoxin-induced IFNI-like gene signature. These results suggest that permeability and DNA sensing responses are driven by parallel pathways downstream of this cytokine, provide new insights into the complex response to acute inflammatory responses, and offer the possibility of potential novel therapeutic strategies for independently controlling the intracellular responses to IL-6 in order to tailor the inflammatory response.

关键词： T lymphocytes   hypertension   inflammation   interleukin   macrophage  

摘要： BACKGROUND:T cells are critical in the pathogenesis of hypertension. IL (interleukin)-16 is primarily produced and secreted by T cells; however, its role in hypertension remains unclear. METHODS:Serum samples from patients with hypertension were collected and analyzed using ELISA. A mouse model of Ang II (angiotensin II)-induced hypertension was established, and the role of IL-16 was investigated. RESULTS:IL-16 expression was elevated in patients with hypertension and positively correlated with both systolic and diastolic blood pressure. In Ang II-induced hypertensive mice, IL-16 expression was significantly upregulated in serum, kidney, and aortic tissues. IL-16-neutralizing antibody reduced both systolic and diastolic blood pressure in response to Ang II. Histological analyses revealed that renal injury and vascular remodeling were attenuated after IL-16 neutralization. Mechanistically, T-cell-derived IL-16 enhanced CD4 (cluster of differentiation 4) T helper 1 cell function and mediated crosstalk with macrophages to stimulate inflammatory responses via activation of NF-κB (nuclear factor kappa B) and MAPK (mitogen-activated protein kinase) pathways. Conditioned medium from macrophages primed with IL-16-treated T helper 1 cells promoted smooth muscle cell proliferation and exacerbated endothelial cell damage during hypertension progression. CONCLUSIONS:Collectively, these findings indicate that T-cell-derived IL-16 exacerbates Ang II-induced hypertension and associated organ damage by promoting a T helper 1-macrophage-driven proinflammatory response.

关键词： 人类白细胞抗原G   复发性妊娠丢失   Th1与Th2细胞的平衡格局  

摘要： 摸索HLA-G表达水平在不明原因复发性流产(RSA)患者免疫保胎治疗里的应用价值,评估联合免疫调节方案对妊娠结局及免疫微环境的影响程度。方法 选取在2022年12月-2024年12月就诊的68例RSA患者,随机把患者分为对照组(n=34,采取常规黄体支持)和观察组(病例有34例,运用地屈孕酮、环孢素A与人免疫球蛋白联合施治,比较两组的妊娠结局、治疗前后HLA-G蛋白的含量水平、Th1/Th2细胞因子的比值、孕7周子宫内膜容受性以及安全性相关指标。结果 观察组临床妊娠率达到94.1%,与对照组的73.5%相比,P等于0.021)与活产率(85.3%相较于52.9%而言,P值达0.004),显著超出对照组水平,流产出现率,P=0.046)出现明显的降低;Th1与Th2比值,P<0.001)出现极显著的数值降低;针对观察组孕7周,其子宫内膜厚度,P<0.001)及子宫动脉血流参数,RI值表现为0.5±0.1与0.7±0.1的对比,呈现出P<0.001的显著改善局面;两组不良反应发生率情况为8.8%对比2.9%,P取值0.303,说明差异无统计学相关意义。结论 联合免疫调节治疗可大幅上调RSA患者HLA-G的表达情况,实现Th1/Th2平衡的调控,增进子宫内膜的容受水平,进而提升临床妊娠几率与活产几率,且呈现出良好的安全特性,为RSA免疫保胎给出新颖策略。