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关键词： 慢性乙肝病毒   慢性乙型肝炎   恩替卡韦   T淋巴细胞   病毒清除  

摘要： 目的 探讨恩替卡韦治疗慢性乙肝病毒(HBV)感染患者辅助性T淋巴细胞(Th)水平及其对病毒清除的影响。方法 选择2020年1月-2024年1月于昆明市延安医院接受恩替卡韦治疗的149例HBV感染患者,其中慢性乙型肝炎(CHB)82例,慢性乙型肝炎病毒携带者(CHBc)67例。依据治疗72周患者血清乙肝表面抗原(HBs Ag)水平分为清除组(64例)和未清除组(85例)。比较两组临床资料,分析治疗期间Th1、Th2水平变化;多元线性回归模型分析治疗期间病毒学改变与免疫水平关系;logistic回归模型分析病毒未清除的危险因素。结果CHBc治疗组与CHB治疗组年龄、基线至24周谷丙转氨酶(ALT)和HBV DNA水平、基线和12周天冬氨酸转氨酶(AST)水平、24周HBs Ag水平、基线Th1、Th1/Th2水平差异具有统计学意义(P<0.05)。HBVDNA、HBs Ag、乙型肝炎E抗原(HBe Ag)水平分别与Th1、Th2、Th1/Th2水平呈线性相关性(P<0.05)。治疗72周累积HBs Ag清除64例,清除率为42.95%,调整混杂因素后多因素分析显示,Th1、Th2和Th1/Th2高水平是病毒未清除危险因素(P<0.05)。结论 HBV感染者中,CHB和携带者免疫水平存在差异,恩替卡韦治疗期间患者Th1、Th2、Th1/Th2水平与HBVDNA、HBs Ag、HBe Ag、病毒清除效率具有强相关性。

关键词： Th9 cells   interleukin-9 (IL-9)   allergies   autoimmunity   cancer   MTOR activation   PPAR-gamma   ACC1  

摘要： Th9 cells are a CD4 T cell subset that produces interleukin-9 (IL-9), a pleiotropic cytokine implicated in allergies, autoimmunity and cancer. Defining the cellular effects of IL-9 and factors regulating its expression are essential for fully understanding its roles in immunity and disease. IL-9 acts on a variety of immune and non-immune cells through a heterodimeric receptor composed of IL-9R alpha and the common gamma chain. In CD4 T cells, IL-9 promotes mTOR activation, aerobic glycolysis, proliferation and reinforces its own expression. Additional cellular effects include mast cell activation, B cell antibody production and anti-tumor immunity. These biological activities are complemented by recent studies that expand our understanding of Th9 differentiation beyond canonical cytokine and transcription factor pathways. Notably, glycolytic reprogramming and fatty acid metabolism have emerged as key regulators of IL-9 production, mediated through the activities of mTOR, PPAR-gamma and acetyl-CoA carboxylase 1 (ACC1). mTOR-driven aerobic glycolysis is essential for Th9 cell differentiation, supporting survival, proliferation, and IL9 expression through HIF-1 alpha activation. In contrast, ACC1 suppresses IL-9 through fatty acid synthesis, which enhances RAR alpha-mediated transcriptional repression. PPAR-gamma appears to have dual functions: it promotes IL-9 production by increasing glucose uptake and activating mTOR, but reduces IL-9 in response to synthetic agonists that may increase fatty acid uptake. Overall, these findings highlight critical roles for metabolic regulators in Th9 responses and suggest that targeting these pathways may offer new therapeutic strategies for IL-9-driven diseases.

关键词： PM2.5   Vc   Thyroid   Ferroptosis   IL-17A signaling pathway  

摘要： Fine particulate matter (PM2.5) is a ubiquitous environmental pollutant that has been demonstrated to affect the thyroid function in women. However, its specific mechanism remains unclear, and protective drugs are deficient. In the present study, we used female rat thyroid models in vivo and rat FRTL5 cell models in vitro to investigate the thyroid toxicity mechanism of PM2.5 and the protective pathway of vitamin C in female rats. PM2.5 exposure caused the production of inflammatory cells in thyroid tissue;transformations of the mitochondrial morphology;increases in the reactive oxygen species (ROS), ferrous ion (Fe2 +), and malondialdehyde (MDA) content in thyroid cells;and decreases in the glutathione peroxidase 4 (GPX4) levels, which resulted in ferroptosis in rat thyroid tissues. In addition, the Interleukin (IL)-17A/IL-17RA/Nuclear factor activator (Act1) signaling pathway was activated by PM2.5. However, vitamin C treatment improved ferroptosis and significantly reduced the expression of the IL-17A, IL-17RA, and ACT1 signaling pathway-related factors. These findings indicate that vitamin C demonstrates protective effects against thyroid injury and ferroptosis, potentially through the inhibition of the IL-17A signaling pathway.

关键词： Diacerein   Intestinal ischemia reperfusion   Interleukin-1 beta   Inflammasome  

摘要： Intestinal ischemia reperfusion (II/R) is an abdominal critical case especially in neonates and during childhood affecting not only the intestinal tissue but also it could damage other remote organs including cardiac tissue even following surgical intervention. Immune homeostasis during II/R has a major role in controlling its progression. Thus, finding additive medical treatment besides the surgical one becomes an urgent need to keep the tissue. So that, we aimed to evaluate the possible ameliorative effect of diacerein (DIA) on II/R-induced injury in juvenile rats. Forty juvenile rats of Wistar albino species were randomly allocated into four different groups: sham group, DIA given group, II/R group via clamping superior mesenteric artery, DIA-treated group (50 mg/kg) with induction of II/R. Data of current model revealed a significant elevation of the measured cardiac enzymes, cleaved caspase-3, and nuclear factor kappa beta (NF-kappa B) in the untreated ischemic group with disturbed oxidative stress parameters, accompanied with dysregulation of inflammasome/caspase-1/IL-1 beta and Wnt/beta-catenin signaling cascades. Fortunately, upon co-administration of DIA, there is a significant decrease of cardiac enzymes, cleaved caspase-3, and NF-kappa B with normalization of oxidative stress parameters and regulation of inflammasome/caspase-1/IL-1 beta and Wnt/beta-catenin pathways confirmed by marked mitigation of the histopathological changes. This effect of DIA is greatly attributed to its pharmacological properties including IL-1 beta antagonist effect, anti-oxidant, anti-apoptotic, and anti-inflammatory properties. Thus, DIA could be considered as an adjuvant future medical therapy for those cases of II/R.

关键词： Zearalenone   TNF   Ovary   Gut microbes   Inflammation  

摘要： As a widely encountered foodborne mycotoxin, Zearalenone (ZEN) has the potential to accumulate along the food chain, posing threats to public health and safety. However, the precise mechanisms by which ZEN causes tissue damage remain incompletely understood. Here, we established in vivo (40 mu g/kg) and in vitro (30 mu M) models to elucidate the underlying processes of ZEN-induced damage to the ovary and intestine. Our results demonstrated that, following ZEN exposure, pro-inflammatory signaling factors, including NLR family pyrin domain containing 3 (NLRP3) and Interleukin 6 (IL6), were significantly elevated in both ovarian and intestines. Metagenomic analysis revealed dysbiosis of the gut microbiota, which was closely associated with tumor necrosis factor (TNF)-alpha signaling pathway. Transcriptomic results further indicated that inflammatory response are intricately linked to TNF signaling pathway. Additionally, the Tnf-alpha knockout mouse model showed a marked resistance to ZEN-induced ovarian and intestinal injuries. In vitro, RNA interference targeting TNF-alpha attenuated the inflammatory response in IPEC-J2 cells. Moreover, dysregulated expression of the hormone synthesis genes, including KISS-1 metastasis suppressor (Kiss1) and gonadotropin releasing hormone 1 (Gnrh1), was observed, suggesting that ZEN-induced microbial dysbiosis and ovary damage may be interconnected through hormonal disruption. In summary, our results emphasize the role of TNF-alpha in causing ovarian and intestinal damage after ZEN exposure.

关键词： Schizophrenia   Interleukin-33   Aggression   Cytokine   Alarmin  

摘要： Aggression in schizophrenia (SCZ) poses a serious risk to others and complicates treatment. Inflammation has been confirmed to be associated with aggression in SCZ, but specific biomarkers remain unidentified. This study aimed to measure plasma interleukin-33 (IL-33) levels and explore their association with aggression in SCZ for the first time. The enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of IL-33 in SCZ with aggression (SCZ-Ag, n = 31) and non-aggression (NSCZ-Ag, n = 32), and healthy controls (HCs, n = 26). Aggression was measured using the Modified Overt Aggression Scale (MOAS), and clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). The results showed that the plasma IL-33 levels were elevated in SCZ-Ag compared with NSCZ-Ag and HCs, with no significant difference between NSCZ-Ag and HCs. In the patient group, partial correlation analysis indicated a positive correlation between IL-33 levels and PANSS total scores, positive symptom subscores, and MOAS total scores. Regression analysis showed that a higher likelihood of aggression in SCZ was associated with elevated plasma IL-33 levels (OR = 1.075, 95 % CI: 1.023-1.129). ROC curve analysis showed that IL-33 (AUC = 0.713, 95 % CI: 0.582-0.844) demonstrated moderate performance in distinguishing SCZ-Ag from NSCZ-Ag. These findings suggest that elevated plasma IL-33 levels are a potential risk factor for aggression in patients with SCZ and are implicated in the clinical symptoms of patients. Increased plasma IL-33 levels may serve as a potential marker for aggression in SCZ. These findings require further validation in future studies.

关键词： Colorectal Cancer   Immunotherapy   MHC class I-related chain A   T cell  

摘要： Background Distant metastasis and immune evasion are the major obstacles for successful colorectal cancer (CRC) treatment. The link between metastasis and immune evasion, as well as their therapeutic significance, remains *** Long non-coding RNAs from six paired CRC and normal tissues were screened by RNA sequencing (RNA-seq). LncRNA-CTD (CTD-2568A17.8) expression levels were determined using in situ hybridization and quantitative PCR analysis. In vitro and in vivo assays were performed to confirm the function of lncRNA-CTD. Flow cytometry was used to analyze the impact of lncRNA-CTD on immune cell infiltration and T-cell function. RNA-seq combined with RNA pull-down and RNA immunoprecipitation assay was used to identify the changes in downstream molecules induced by lncRNA-CTD. The therapeutic value of the combination of lncRNA-CTD and immune checkpoint inhibitors has been *** In this study, we identified a novel long non-coding RNA, lncRNA-CTD, which is downregulated in CRC and correlates with both metastasis and immunotherapy response. Mechanistically, the interaction of lncRNA and smad2 prevented the phosphorylation and nuclear translocation of smad2, which inhibited the expression of snail1, thereby inhibiting the metastasis of CRC. LncRNA-CTD enhances major histocompatibility complex class I (MHC-I) expression on the cancer cell membrane by interacting with STUB1 to disrupt the interaction of STUB1 with the MHC-I activator NLRC5 and subsequent NLRC5 ubiquitination-mediated degradation, increasing the susceptibility of CRC cells to being killed by CD8+ T cells. TFAP4 overexpression in CRC cells caused lncRNA-CTD downregulation. Moreover, the combination of lncRNA-CTD gene delivery therapy with immune checkpoint inhibitors exerted an additive effect on tumor growth *** Collectively, our study reveals the role and mechanism of lncRNA-CTD in CRC metastasis and immune evasion. Overexpression of lncRNA-CTD suppresses CRC

关键词： Malaria   Medical risk factors   Anemia   Iron deficiency anemia   Ghana   Malarial parasites   Alleles   Polymerase chain reaction  

摘要： Background of the study Malaria is a paramount health concern mostly among infants and young children. The World Health Organization recommends iron fortification for children with iron deficiency anaemia living in malaria-endemic regions like Ghana. However, the intricate interplay between genetic polymorphisms and nutritional interventions in malaria susceptibility and severity remains unclear. The Human Leukocyte Antigen-G (HLA-G) locus within the Major Histocompatibility Complex (MHC) genes has surfaced as a critical player in regulating immune responses and influencing disease outcomes. Therefore, we aimed to evaluate the effect of HLA-G 14 bp polymorphism and its associated risk of malaria severity among Ghanaian infants and young children on iron *** This secondary double-blinded cluster randomized controlled trial involved 432 archival samples from the Tain District and Wenchi Municipal in the Bono Region. Participants aged between 6 and 36 months and consuming semi-solid foods were recruited in the study while children with malaria infection or other known medical conditions were excluded. Capillary blood samples were taken for anaemia determination using a haematology autoanalyzer, malaria infection status, and parasitaemia were assessed via microscopy, and HLA-G 14 bp polymorphism using PCR. Hardy-Weinberg equilibrium and multivariate regression models were used to analyze the data *** The research findings indicate that among the iron-fortified children with HLA-G, 14 bp + /- and 14 bp-/- variants are likely to develop severe malaria. Also, the HLA-G 14 bp + /- variant was linked to a higher risk of anaemia development among participants who received iron *** The study results indicated that iron-fortified individuals carrying the HLA-G 14 bp insertion/deletion polymorphism have an elevated risk of developing severe malaria, which in turn predisposes them to anaemia.