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关键词： Interleukin-33   Ischemic stroke   Immunosuppression   Inflammation  

摘要： Cerebrovascular disease is the second-leading cause of death and disability worldwide, with stroke being the most common cause. In ischemic stroke, several processes combine to produce immunosuppression, leaving the post-stroke body susceptible to infection, which in turn affects neuroinflammation. Interleukin-33 (IL-33), a member of the interleukin-1 family (IL-1), functions as a modulator of immune responses and inflammation, playing a crucial role in the establishment of immunologic responses. IL-33 has been shown to have a protective effect on brain injury and represents a potential target by modulating inflammatory cytokines and stimulating immune regulatory cells. With an emphasis on preclinical and clinical studies, this review covers the impact of IL-33 on immune system mechanisms following ischemic stroke.

关键词： adalimumab   inflammatory bowel disease   infliximab   paradoxical psoriasis   TNF-alpha inhibitors  

摘要： Paradoxical psoriasis is a well-described phenomenon following treatment with Tumour Necrosis Factor alpha (TNF-alpha) inhibitors in adult patients with Inflammatory Bowel Disease (IBD). The incidence and optimal treatment strategies are not well described in children with IBD. This subgroup of patients is disproportionately impacted by TNF-alpha inhibitor-induced psoriatic eruptions. Our systematic review and meta-analyses aims to describe the incidence, presentation, and management options for TNF-alpha inhibitor-induced psoriasis in paediatric patients with IBD. A systematic literature search was conducted using Medline, Embase and Cochrane databases for studies published up to February 2025. Retrospective cohort studies (n = 16), prospective cohort study (n = 1), and a cross-sectional study (n = 1) met inclusion criteria. Studies focusing on patients > 18 years or TNF-alpha inhibitors used for non-IBD conditions were excluded. A total of 3349 paediatric patients with IBD treated with TNF-alpha inhibitors were analysed, with 255 (7.6%) developing paradoxical psoriasis. Meta-analysis of 13 studies meeting sample size criteria yielded a pooled incidence of 6.8% (95% CI: 0.04-0.10). Infliximab (IFX) accounted for 151 (79.1%) of cases, whereas adalimumab (ADA) contributed to 40 (20.9%) cases. The median time to clinical eruption was 15.0 months (12.0-18.0). Among affected patients, 22.3% (51/229) discontinued their prescribed TNF-alpha inhibitor and 5.7% (13/229) were subsequently switched to an alternative TNF-alpha inhibitor. Ustekinumab (UST) was the most common non-TNF-alpha alternative (14/94). TNF-alpha inhibitor-induced psoriasis is a common adverse effect in paediatric IBD, with a significant proportion of cases necessitating treatment discontinuation. Long-term outcomes following a switch to non-TNF-alpha biologics remain unclear, highlighting the need for further prospective studies.

摘要： OBJECTIVE: The key to maintaining pregnancy is the balance between pro-inflammatory and anti-inflammatory responses, in which immune cells such as B and T lymphocytes play a pivotal role. While the function and regulation of B-regulatory cells (Br...

关键词： oocyte donation   pre-eclampsia   decidua   HLA   myeloid cells  

摘要： OBJECTIVE: Healthy pregnancy requires local tolerogenic immune mechanisms. Pregnancies after oocyte donation (OD) are related to more fetal-maternal HLA mismatching and to elevated risk of pre-eclampsia. We hypothesize that in OD pregnancies with ...

关键词： Cyclophosphamide   Sakuranetin   Immunosuppression   Cytokines   Immunoglobulin   Interleukins  

摘要： Cyclophosphamide is a widely used chemotherapeutic agent known for its effectiveness in treating various cancers;however, it is associated with significant immunosuppressive side effects. This study investigates the potential of sakuranetin, a natural flavonoid, in mice under cyclophosphamide-induced immunosuppressive conditions. Mice were grouped into four groups: one control group, two treated with cyclophosphamide and two sakuranetin-treated groups receiving different doses (10 and 20 mg/kg). Immune organ indices, lymphocyte proliferation, hematological parameters, nitric oxide levels, cytokines (tumor necrosis factor alpha-TNF-alpha, interferon gamma-IFN-gamma), interleukins (interleukin-1 beta-IL-1 beta, IL-4, IL-6), immunoglobulin G (IgG), IgM levels, plague-forming cells quantification, qualitative hemolysis, and delayed-type hypersensitivity were assessed. Cyclophosphamide significantly (P < 0.05) reduced immune organ indices, lymphocyte proliferation, changes in hematological parameters, and nitric oxide levels. Treatment with both sakuranetin doses restored these parameters and normalized cytokine, IgG, and IgM levels (P < 0.05). Sakuranetin significantly (P < 0.05) improved the immunomodulatory action with elevated immune response with downregulation in immune response mediated by cells. Sakuranetin effectively counteracts cyclophosphamide-induced immunosuppression by modulating the IFN-gamma, TNF-alpha, IgG, and interleukin pathway, suggesting its potential as a protective agent.

关键词： Exosomes   EVT   HLA class I molecules  

摘要： OBJECTIVE: Acceptance and support for the semi-allogeneic embryo and effective protection of both mother and fetus are required for a successful pregnancy. Placenta-derived exosomes have a crucial role in human implantation and pregnancy. Exosomes...

关键词： HLA-G 14-bp   meta-analysis   polymorphism   recurrent spontaneous abortion  

摘要： We performed a meta-analysis to study the relationship between HLA-G 14-bp insertion/deletion polymorphism and recurrent spontaneous abortion (RSA). All literature was searched from PubMed, Web of Science, Embase and Wanfang databases. Statistical analyses were performed by the STATA software (Version 16.0). A total of 35 studies were analysed which included 3652 women with RSA and 3331 normal control subjects. The current meta-analysis revealed that 14-bp insertion/deletion polymorphism has a significant association with RSA (I vs. D: OR: 1.17;95% CI (1.05-1.30);II + ID vs. DD: OR: 1.33;95% CI (1.11-1.59);II vs. DD: OR: 1.34;95% CI (1.07-1.66);ID vs. DD: OR: 1.30;95% CI (1.08-1.58)). Subgroup analysis by the number of abortions indicated that there was no significant association between HLA-G 14-bp insertion/deletion polymorphism and RSA risk in women with two or more abortions. However, HLA-G 14-bp insertion/deletion polymorphism was associated with the risk of RSA in women with three or more abortions as well as the overall population (I vs. D: OR: 1.26;95% CI (1.04-1.52);II + ID vs. DD: OR: 1.47;95% CI (1.09-1.98);II vs. DD: OR: 1.52;95% CI (1.08-2.13);ID vs. DD: OR: 1.45;95% CI (1.06-1.99)). Subgroup analysis by ethnicity indicated that HLA-G 14-bp insertion/deletion polymorphism increased RSA risk in both Asian ancestry group (II + ID vs. DD: OR: 1.35;95% CI (1.06-1.73);ID vs. DD: OR: 1.37;95% CI (1.06-1.78)) and European ancestry group (I vs. D: OR: 1.25;95% CI (1.08-1.45);II vs. ID + DD: OR: 1.48;95% CI (1.14-1.91);II vs. DD: OR: 1.61;95% CI (1.19-2.18)). A pOR value of < 0.05 was considered statistically significant for these analyses. Our current meta-analysis demonstrated that the HLA-G 14-bp insertion/deletion polymorphism increased the risk of RSA in Asian ancestry group and European ancestry group.

关键词： Retinal Pigment Epithelium   DNA Repair   Serine and Arginine Rich Splicing Factor 1   Interleukin-6  

摘要： Chronic inflammation has been associated with the progression of age-related macular degeneration (AMD) and diabetic retinopathy (DR), and the levels of various inflammatory factors are significantly increased in intraocular fluids of patients with AMD and DR. Therefore, elucidating the roles of inflammatory factors in the oxidative damage of RPE cells will help uncover the pathogenesis of AMD and DR. We have previously demonstrated that E2F1 plays an important role in the antioxidant capacity of RPE cells. Here, our transcriptome analysis shows that E2F1 affected the expressions of DNA repair genes in RPE cells. In addition, we found that E2F1 transactivated the splicing factor SRSF1. SRSF1 knockdown promoted DNA oxidative damage and apoptosis and decreased the mRNA stability of DNA repair genes XRCC2, POLK and LIG4 in RPE cells. Moreover, we found that SRSF1 could bind to the RNA stabilizing factor MATR3, and knockdown of the latter affected the mRNA stability of these DNA repair genes. Notably, interleukin-6 (IL-6), an inflammatory factor upregulated in intraocular fluids of patients with AMD and DR, decreased SRSF1 expression by inducing acetylation of E2F1 at the K125 position. Consistently, SRSF1 overexpression relieved IL-6-induced DNA oxidative damage and apoptosis in RPE cells. In vivo experiment results also confirmed that IL-6 could aggravate retinal oxidative damage. In conclusion, high levels of IL-6 in the eyes of patients with AMD and DR destabilize the mRNAs of DNA repair genes by disrupting the expression of SRSF1, leading to abnormal repair of DNA oxidative damage in RPE cells.

关键词： duck   Ii   MHC   localization   binding interaction  

摘要： Objective To investigate the intracellular localization and binding of duck invariant chain (Ii) to major histocompatibility complex (MHC) class I alpha or MHC class II beta molecules. Methods First, the genes of duck Ii, MHC I alpha, and MHC II$ were amplified by PCR, cloned into expression plasmids, and then sequenced to compare homology between ducks and selected agricultural species. Second, Rosetta or 293T cells were transfected with plasmids encoding Ii, MHC I alpha, and MHC II beta either alone or in combination to interrogate bind-ing following expression. The fluorescent reporter molecules used to tag/image transfected cells and expressed pro-tein were identified by western blot. Additionally, the binding interaction of the expressed products was observed by affinity purification using pull-down assay and coimmunoprecipitation. Finally, intracellular colocalization was observed by laser confocal microscopy. Results The results of western blots demonstrated that all constructed plasmids successfully expressed proteins. Pull down and coimmunoprecipitation revealed that Ii could bind I alpha or II beta, forming Ii-I alpha or Ii-II beta complexes, and they dissoci-ated into single molecules after SDS treatment. In 293T cells, Ii interacts with MHC I alpha or MHC II beta chains and colo-calizes intracellularly. Confocal fluorescence microscopy assay indicated that MHC I alpha and II beta were located in the endoplasmic reticulum and endosome. Conclusions Both MHC and Ii proteins exhibit direct interactions and can colocalize in the endoplasmic reticulum and endosomes. Clinical Relevance This study investigates the relationship between duck Ii and MHC proteins, offering a theoretical foundation for exploring the role of Ii in immune responses and advancing the development of Ii-vectored avian vaccines.

关键词： Inflammaging   Insulin   Interleukin-34   Metaflammation   Pancreas  

摘要： Interleukin-34, a ligand of CD115, controls Langerhans cells and microglia homeostasis and acts as regulatory cytokine. Here, we describe an unexpected role for IL-34 in metabolic homeostasis. We show that IL-34 is constitutively expressed by human n-cell and mouse islets of Langerhans. n-cell specific genetic invalidation of Il34 in mice (IL-34 Delta Pdx) impaired glucose tolerance associated with increased inflammation in islets of Langerhans during aging. This phenotype was exacerbated when IL-34 Delta Pdx mice were subjected to a high-fat diet, suggesting a role for IL-34 in controlling local inflammation. Accordingly, in the presence of pro-inflammatory cytokines, ex vivo murine islets of Langerhans exhibited a decreased insulin synthesis, which was restored in the presence of IL-34. Finally, we observed that the levels of Il-34 mRNA were elevated in islets of Langerhans from type 2 diabetic donors. Collectively, these results identify IL-34 as a major regulator of pancreas inflammation.