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关键词： SARS-CoV-2   inflammatory response   genetic polymorphisms   disease severity   Brazilian population  

摘要： Background/Objectives: Genetic variants in cytokine genes such as IL1B, IL6, and TNF may influence inflammatory responses to SARS-CoV-2 and affect disease severity. This study investigates the role of these variants in relation to COVID-19 outcomes, including hospitalization, ICU admission, and mortality. Methods: A total of 500 unvaccinated individuals from southern Brazil diagnosed with COVID-19 via RT-PCR were analyzed. DNA was extracted from nasopharyngeal swabs and genotyped for functional variants selected based on evidence of regulatory function and prior associations with inflammatory outcomes-IL1B (rs4848306, rs1143623, rs16944, rs1143627), IL6 (rs1800795, rs2069832, rs2069840, rs2069845), and TNF (rs1799964, rs1800630, rs1799724, rs1800629, rs361525). Multivariate logistic regression analysis, adjusted for sex and age, was employed to assess the association between these genetic variants and severe clinical outcomes. Results: The results indicated that the IL1B rs16944-AG (OR: 1.98 [95% CI: 1.22-3.23], p = 0.006) and TNF rs1799964-CT (OR: 1.97 [95% CI: 1.22-3.22], p = 0.006) genotypes were associated with the need for hospitalization, while TNF rs1800630-AA (OR: 2.37 [95% CI: 1.08-5.33], p = 0.034) was associated with ICU admission. Additionally, the CC genotype of TNF rs1799964 was associated with a higher risk of mortality (OR: 3.73 [95% CI: 1.21-14.37], p = 0.034). Conclusions: Genetic variants-specifically IL1B rs16944 and rs1143627, and TNF rs1799964 and rs1800630-were associated with COVID-19 severity and should be further investigated in larger studies to evaluate their potential as predictive markers of severe outcomes in COVID-19.

摘要： Several theoretical studies have concluded that heterozygote advantage makes at most a minor contribution to MHC diversity. Siljestam and Rueffler (2024) recently presented models in which heterozygote advantage alone can lead to realistically high diversity. Here I argue that heterozygote advantage cannot by itself explain MHC diversity, and that its contribution to diversity is unlikely to be large in most species. I first show that the high diversity reported by Siljestam and Rueffler is so sensitive to parameter values that the underlying phenomenon cannot explain the widespread diversity of MHC genes. I then consider a fundamental problem with explaining MHC diversity by heterozygote advantage alone: selective forces that favored heterozygotes would lead to the evolution of haplotypes having much higher fitness when homozygous, diminishing or eliminating heterozygote advantage. Diversity maintained by another force, however, might bring about adaptation to the more common heterozygous state at the expense of homozygous fitness. Thus, substantial heterozygote advantage may arise as a consequence of MHC diversity.

关键词： Breast Cancer   B cell   Tumor microenvironment - TME  

摘要： Background Breast cancer is the leading cause of cancer-related deaths among women globally. Tumor-secreted proteins foster an immunosuppressive environment, enabling immune evasion and reducing the effectiveness of antitumor immunity. Interleukin (IL)-10, an immune-regulatory cytokine, is upregulated in breast cancer (BRCA), but the underlying mechanism remains *** In silico analysis was used to identify candidate genes associated with IL-10 expression. Mouse model of BRCA and in vitro co-culture assays were conducted to identify immune cells responsible for IL-10 upregulation. The efficacy of galectin-3 (Gal-3) inhibition combined with chemotherapy was also *** Tumor-secreted Gal-3 served as a key immunosuppressive factor in BRCA. Gal-3 promoted IL-10 production in B cells, thus impairing antitumor immunity. Mechanistically, Gal-3 triggered CD45 polymerization, reducing its phosphatase activity and subsequently activating STAT3 to promote IL-10 production. Knockdown of STAT3 or its blockade abrogated Gal-3-induced IL-10 upregulation. Furthermore, Gal-3 inhibition combined with chemotherapy significantly reduced tumor growth and enhanced antitumor *** Gal-3 is a crucial regulator of immune evasion in BRCA. Targeting Gal-3 may improve the efficacy of BRCA therapies.

关键词： autoantibody dynamics   biologic therapy   bullous pemphigoid   IL-23p19 inhibitors   immunopathogenesis   psoriasis   psoriatic arthritis  

关键词： diabetic foot   prognosis   interleukin-6   intercellular adhesion molecule-1   soluble suppression of tumorigenicity 2  

摘要： Diabetes foot (DF) is one of the most serious chronic complications of diabetes. This study explored the relationship between serum interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and soluble suppression of tumorigenicity 2 (sST2) and wound prognosis in 210 DF patients between January 2019 and January 2024. 210 DF patients were divided into the good prognosis (n = 147) and poor prognosis (n = 63) group according to the prognosis. Comparative analysis revealed that levels of serum IL-6, ICAM-1 and sST2 in the poor prognosis group were all higher than those in the good prognosis group significantly (P < .05). Multivariate logistic regression identified these 3 biomarkers as independent risk factors for poor wound healing (P < .05). Positive correlations between serum IL-6 (r = 0.269), ICAM-1 (r = 0.302), sST2 (r = 0.289) levels and poor prognosis were confirmed through Pearson's correlation analysis. A prediction model was established to analyse their predictive value. The training and validation sets ROC curves had AUCs of 0.79 (0.71-0.87) and 0.75 (0.59-0.91) respectively. Calibration curves were plotted to evaluate the consistency of the model, and the results showed that the predictive value of the nomogram model was similar to that of the actual one. Decision curves were plotted, which showed that the nomogram had higher positive net benefit in the range of 20% to 60%. This study suggest that serum IL-6, ICAM-1, and sST2 levels may serve as valuable prognostic indicators for wound healing progression in DF patients, with combined biomarker assessment showing potential clinical utility for outcome prediction. The total sample size (n = 210), with validation set (n = 63) of this study are relatively limited and the representativeness is restricted, which may affect the universality of the research conclusions.

关键词： 头孢噻肟钠舒巴坦钠   迟发型超敏反应   药品不良反应   第三代头孢菌素   皮疹  

摘要： 目的 探讨头孢噻肟钠舒巴坦钠致迟发型超敏反应的临床特征、判断方法和治疗策略，为临床安全用药提供参考。方法 分析1例使用头孢噻肟钠舒巴坦钠后发生迟发型超敏反应的病例，归纳总结相关处理方案。结果 因间断性干咳被诊断为肺占位性病变并伴有2型糖尿病患者，在接受包括头孢噻肟钠舒巴坦钠在内的综合性治疗6 d后，出现了超敏反应，临床表现为双下肢和面部皮疹伴瘙痒，鉴于症状与头孢噻肟钠舒巴坦钠已知不良反应症状和注射时间的高度相关性，故怀疑是该药致迟发型超敏反应，随即停用该药并予抗过敏治疗，患者症状缓解，生命体征平稳。结论 应注意头孢噻肟钠舒巴坦钠的迟发型超敏反应风险，其特点是有一定的潜伏期，应加强观察，综合判断，及时停药，必要时予抗过敏治疗。

摘要： Interleukin-2 (IL-2) is a pivotal cytokine that plays a crucial role in the activation, proliferation, and functional regulation of multiple immune cells. High-dose IL-2 has been approved for antitumor therapy but may cause toxicity. IL-2 levels within the body are also associated with various pathological states, making it a potential diagnostic and prognostic biomarker. Consequently, the development of efficient tools for the rapid detection and real-time quantification of IL-2 is of great significance. In this study, we identified two human IL-2-binding aptamers, Apt24 and Apt35, through the systematic evolution of ligands by exponential enrichment (SELEX). On this basis, we constructed two aptamer beacons to detect IL-2 proteins in solution. Further, we successfully developed a membrane-anchored aptamer sensor, Chol-Apt35, to realize in situ detection of IL-2 secretion in living cells. The sensor exhibits good membrane-insertion ability and performs comparably with fluorescent antibodies. In conclusion, this study provides simple yet effective tools for IL-2 detection, which may facilitate dose optimization in immunotherapy and assessment of immunological status.

关键词： Chronic lymphocytic leukemia   Type 2 innate lymphoid cells (ILC2s)   IL-9   Regulatory T cells (Treg)   CD8(+) T cells  

摘要： Objective This study investigated the impact of innate lymphoid cell type 2 (ILC2s) on the function of regulatory T cells (Treg) and CD8(+) T cells in chronic lymphocytic leukemia (CLL) through IL-9. Methods Peripheral blood samples were collected from CLL patients (n = 52) and healthy controls (n = 30). ILC2 proportions and IL-9 levels were assessed using flow cytometry and ELISA. Immunofluorescence staining was performed to stain GATA3, CRTH2, and IL-9 in cervical lymph nodes from CLL patients (n = 10) and control subjects with reactive lymphadenitis (n = 10). Correlation analysis between ILC2s and IL-9 was conducted using the Spearman test. ILC2s were sorted and cultured from CLL patients, followed by co-culture experiments with PBMCs of healthy controls and MEC-1 cells, with or without anti-IL-9 antibody intervention. Flow cytometry was used to measure the proportions of ILC2s, Treg cells, PD-1(+)/TIGIT(+)/CTLA-4(+) Treg subsets, and granzyme B+/perforin(+) CD8(+) T cells, along with MEC-1 cell apoptosis. Results The proportions of ILC2s and Treg, along with serum IL-9 levels, were significantly elevated in CLL patients (P < 0.05). Peripheral blood ILC2s were positively correlated with IL-9 (r = 0.609, P < 0.001). The average fluorescence intensity of GATA3, CRTH2, and IL-9 in the cervical lymph nodes of CLL patients increased significantly (P < 0.001), and IL-9 showed colocalization with GATA3 and CRTH2. In vitro, IL-9 levels in the supernatant of sorted ILC2s from CLL patients increased. Treatment with anti-IL-9 antibody significantly reduced the PD-1(+) Treg and TIGIT(+) Treg cells while increasing granzyme B+ CD8(+) T cells (P < 0.05). However, there was no significant effect on Treg, CTLA-4(+) Treg, and perforin(+) CD8(+) T cells (P > 0.05). Additionally, anti-IL-9 antibody significantly increased early apoptosis (P < 0.05). Conclusion ILC2s affect CD8(+) T cells and Treg cells through IL-9, weakening the anti-tumor effects of CD8(+) T cells and enhancing t

关键词： Macrophages   Eggs   Schistosoma mansoni   Cloning   Cytokines   Collagens   Fibrosis   Liver fibrosis  

摘要： Tissue damage in Schistosoma mansoni infection results from a granulomatous, T cell-mediated response to parasite eggs, leading to liver fibrosis and portal hypertension. This immune response, initially Th1-dominated, progressively shifts toward a Th2 profile, contributing to hepatic stellate cell (HSC) activation and fibrosis. However, the precise regulatory mechanisms remain unclear. In this study, we analyzed T cell responses to soluble egg antigens (SEA) in 121 T cell clones (Tcc) from S. mansoni-infected patients. All clones produced high levels of IL-13 upon anti-CD3 stimulation; a minority secreted IFN-γ (n = 33) or IL-10 (n = 38). Notably, 51 clones co-produced IL-22 and IL-13. To investigate IL-22's role, we examined IL-22 receptor (IL-22R) expression on human M0 and M2 macrophages. Both subsets expressed IL-22R, and its engagement triggered phosphorylation of p38, STAT3, and STAT5. IL-22 also downregulated IL-13-induced M2 markers (CD163, CD200R). Furthermore, IL-22 treatment of HSCs inhibited IL-13-driven collagen I/III production and cell proliferation. These results suggest that IL-22-producing T cells modulate Th2 macrophage polarization and directly suppress fibrogenesis in HSCs. IL-22 may thus act as a regulatory cytokine counteracting liver fibrosis during schistosomiasis.