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关键词： Bronchial asthma   Gene mutation   Genetic variation   IL-13  

摘要： Genetic polymorphisms in interleukin-13 (IL13) gene have been associated with asthma susceptibility in different ethnicities. We investigated the association of two polymorphisms in the IL13 gene [rs1800925 (c.-93+487C>T), and rs20541 (***144Arg)] with asthma susceptibility among Sudanese patients. A case-control study was conducted at Al-Shaab Teaching Hospital between April and October 2022. Involving fifty asthmatic patients and fifty controls. The genotypes were determined using an allele-specific polymerase chain reaction. For rs1800925, a significant association with asthma in multivariate analysis (aOR=3.15, 95% CI: 1.13-8.76;p=0.028). The T allele was the most frequent in cases and showed a significant association with asthma (aOR=1.99, 95% CI: 1.13-3.5;p=0.016). The rs20541 did not show any association with asthma. The rs1800925 is associated with an increased risk of asthma in Sudanese patients.

摘要： Background:Three biologics targeting interleukin 5 (anti-IL-5) or its receptor-α (anti-IL-5Rα) are approved for patients with severe asthma. Methods:We systematically searched the literature published in Medline and Embase up to 1 May 2023 to identify observational studies and nonrandomised trials that assess the response to anti-IL-5/5Rα in real-life patients with severe eosinophilic asthma. We also performed random-effects meta-analyses. Results:We identified 6401 studies, of which 92 with 9546 patients were analysed. Biologics use was associated with a 62% reduction in severe exacerbations (risk ratio 0.38, 95% CI 0.29-0.50) and a 54% reduction in hospitalisations (risk ratio 0.46, 95% CI 0.35-0.61) at 12 months of treatment, compared to pre-treatment. Biologics improved asthma control (decrease in asthma control questionnaire score by 1.11 points (95% CI -1.29--0.94) and increase in asthma control test score by 6.41 points (95% CI 5.66-7.16)) and increased the asthma quality of life questionnaire score by 1.08 points (95% CI 0.88-1.28) and forced expiratory volume in 1 s by 0.21 L (95% CI 0.15-0.27) at 12 months. There was a significant reduction in oral corticosteroids use of 51% (risk ratio 0.49, 95% CI 0.42-0.56), with a mean dose reduction of 6.01 mg·day (95% CI -7.55--4.48) at 12 months of treatment. Similar findings were observed at 3-4, 6 and 24 months. A biomarker-related response to treatment was also noted. Conclusions:This comprehensive meta-analysis summarises the significant clinical response to anti-IL-5/5Rα biologics in real-life studies, providing important insights for their use in clinical practice.

关键词： COVID-19   IL-6   Polymorphism   rs1800795   rs1800796   Severity of disease   Turkish population  

摘要： Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is exacerbated by cytokine storms, leading to severe inflammation. Interleukin-6 (IL-6) plays a critical role in this process, and variations in its promoter may influence disease severity. This study aims to investigate the relationship between IL6 promoter polymorphisms rs1800795 (G > C) and rs1800796 (G > C) and the severity of COVID-19 in the Turkish population. A total of 332 participants were included: 84 control, 80 with mild COVID-19, and 168 with severe COVID-19. IL6 polymorphisms were genotyped using the restriction fragment length polymorphism (RFLP) method. The genotypes rs1800795 GC (OR = 3.00, 95% CI: 1.669-5.398, p < 0.000), CC (OR = 7.44, 95% CI: 2.899-19.131, p < 0.000), and rs1800796 GC (OR = 2.76, 95% CI: 1.603-4.761, p < 0.000), as well as the alleles rs1800795 C (OR = 3.01, p < 0.000) and rs1800796 C (OR = 1.97, p = 0.002), may be associated with the severity of COVID-19. According to the Jonckheere-Terpstra (J-T) test, the most significant trends that vary linearly with disease severity were observed for D-dimer [J-T = 15.896, Effect size = 0.68 (0.61 to 0.76), p < 0.000] and CRP [J-T = 15.389, Effect size = 0.66 (0.59 to 0.73), p < 0.000]. The distribution of clinical parameters across genotype combinations (rs1800796/rs1800795*) showed that GC/GC* and GC/CC* were linked to a higher risk of severe inflammation, clotting, and organ damage. Additionally, it has been determined that the G-C and C-C haplotypes may be associated with increased severity of COVID-19. The rs1800795 and rs1800796 polymorphisms are linked to COVID-19 severity and could help guide future treatment strategies.

关键词： IL-10RA   Energy metabolism   FAO   NSCLC   STAT3 signaling pathway  

摘要： Metabolic reprogramming in tumor cells plays a crucial role in promoting cell proliferation and metastasis, and is currently recognized as a significant marker of tumor progression. Interleukin-10 receptor subunit alpha (IL10RA), a member of the type II cytokine receptor family, is predominantly expressed on macrophages and T cells and plays a crucial role in regulating immune cell metabolism and immune response. However, its role in the energy metabolic pathways of tumor cells remains unclear. In this study, we found increased expression of IL10RA in human non-small cell lung cancer (NSCLC), and a correlation between increased IL-10RA expression and tumor stage, tumor size, and short overall survival of patients with NSCLC. IL-10RA overexpression significantly promoted the proliferation of NSCLC cell lines and enhanced glycolysis and fatty acid oxidation (FAO), thereby boosting energy production. Correspondingly, the downregulation of IL-10RA inhibited proliferation, glycolysis, and FAO in NSCLC cell lines. Bioinformatic analyses indicated that IL-10RA upregulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. STAT3 inhibitor effectively blocked the increase in FAO levels and cell proliferation induced by IL-10RA overexpression. These findings suggest that IL-10RA accelerates NSCLC cell proliferation by increasing FAO levels via the STAT3 pathway, highlighting IL-10RA as a potential therapeutic target for NSCLC.

关键词： HLA   HLA-C*04:534   novel allele   sequencing-based typing  

摘要： HLA-C*04:534 differs from HLA-C*04:01:01:01 by two nucleotide substitutions in codons 166 and 167 in exon 3.

关键词： B cell malignancies   CD19 CAR T   Immune response   M5C   M6A   MHC   RNA modification   Selective inhibitor   Tumor microenvironment   YTHDF2  

摘要： RNA -methyladenosine (mA) modification has been identified as the most abundant RNA modification and plays crucial roles in both physiological and pathological processes. YTHDF2 was the first identified reader protein that can recognize mA modification and recent studies also revealed its ability to bind 5-methylcytidine (mC) modification. YTHDF2 shows a dual binding capacity to both mA and mC, which leads to opposite mRNA outcomes. Multiple studies have highlighted the critical roles of YTHDF2 in tumor development and tumor microenvironment. Emerging findings showed that YTHDF2 plays critical roles in immune regulation, impacting T cell, B cell, NK cell, macrophage, innate/adaptive anti-tumor immune responses, and T-cell based immunotherapy. Inhibitors have been developed to target YTHDF2, which showed potential efficacy in tumor treatment. Herein, we reviewed the molecular mechanism of YTHDF2 and its roles in tumors, immune cells, and tumor microenvironment.

关键词： Unresectable hepatocellular carcinoma   Atezolizumab plus bevacizumab   Interleukin-6  

摘要： Background This study aims to identify biomarkers for treatment response of atezolizumab plus bevacizumab (Atezo+Bev) in patients with hepatocellular carcinoma (HCC). Methods 96 patients who received Atezo+Bev or lenvatinib as a first-line systemic therapy were enrolled as the training group after propensity score matching (PSM), and 42 patients treated with Atezo+Bev were enrolled as the validation group. 17 serum cytokines were measured by Luminex multiplex assay at the start of treatment. For further assessment of the association between cytokine levels and the tumor microenvironment (TME), immunohistochemistry (IHC) was performed on pre-treatment liver biopsy specimens. Results In the derivation set, multivariate analysis identified elevated IL-6 as an independent risk factor in the Atezo+Bev group (HR 5.80: p<0.01), but not in the lenvatinib group;in a subset analysis of patients with low IL-6, PFS was longer in the Atezo+Bev training group than in the lenvatinib group (p = 0.02). A validation study also showed a significantly longer prognosis in the low IL-6 group for both PFS (p = 0.0001) and OS (p = 0.03). Serum IL-6 had a positive correlation with tumor IL-6 expression (rho = 0.56, p < 0.0001) and an inverse correlation with the CD8/CD163-positive cell count ratio (rho = -0.4, p < 0.01). Conclusion Serum IL-6 levels are thought to be involved in the suppression of tumor immunity and are useful in predicting the therapeutic effect of Atezo+Bev treatment.

关键词： HLA-DQB1*06:01:01:09 novel allele   Illumina   next-generation sequencing  

摘要： The HLA-DQB1*06:01:01:09 allele differs from HLA-DQB1*06:01:01:01 by a single nucleotide substitution in intron 2.

关键词： DC-SIGN   IL-10   anti-inflammatory effects   veterinary autoimmune diseases   veterinary immune-mediated diseases   DC-SIGN ligands   DC-SIGN homologues in animals   comparative medicine   translational research  

摘要： DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) is a C-type lectin receptor expressed on dendritic cells and M2 macrophages, playing a key role in immune regulation and pathogen recognition. Its ability to mediate anti-inflammatory effects by interacting with specific ligands triggers pathways that suppress pro-inflammatory responses and promote tissue repair, making it a potential therapeutic target for inflammatory and autoimmune diseases. DC-SIGN homologs in various animal species share structural similarities and perform comparable immune functions, offering valuable insights into its broader application across species. By recognizing carbohydrate ligands on pathogens, DC-SIGN facilitates immune modulation, which can be harnessed for developing therapies aimed at controlling inflammation. In veterinary medicine, autoimmune and inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, represent significant challenges, and the anti-inflammatory properties of DC-SIGN could provide new therapeutic options to improve disease management and enhance animal health. Future investigations should focus on the structural and functional analysis of DC-SIGN homologs in various species, as well as the development of preclinical models to translate these findings into clinical interventions bridging veterinary and human health.

关键词： allergy   cytokine   human   IgE   inflammation   lectin   tumor immunity  

摘要： Galectin-3 (Gal-3) is implicated in innate immune cell activation in a host of diseases/conditions. We identified a unique response whereby human basophils secrete interleukin (IL)-4/IL-13 when cocultured with A549 cells-lung adenocarcinoma. While displaying parameters consistent with standard IgE-dependent activation, these Gal-3-dependent responses occurred in the absence of specific IgE/allergens and required cell-to-cell contact. We now hypothesize that this mode of activation also impacts A549 function. Our findings show that cytokines are induced in basophil/A549 cocultures that are not detected when either cell is cultured alone, in particular IL-6. As previously shown for IL-4/IL-13, IL-6 production also required cell-to-cell contact and was dependent on A549- Gal-3, as clones deficient of this lectin induced less cytokine. Using culture-derived basophils (CDBAs), we demonstrate that the IL-6 response and production of another tumorigenic factor, vascular endothelial growth factor A (VEGF-A), are induced in CDBA/A549 cocultures but only after passively sensitizing CDBAs with IgE, in a manner similar to IL-4/IL-13. However, IgE-dependent activation of basophils/CDBAs cultured alone failed to induce IL-6/VEGF. Importantly, IL-3-primed basophils, even those fixed with paraformaldehyde, readily induced IL-6/VEGF-A in cocultures, thus verifying that these cytokines are derived from A549. Overall, these results suggest a complex mechanism whereby Gal-3/IgE interactions between IL-3-primed basophils and A549 have the potential to modulate cytokine production by both cells. With Gal-3 implicated not only in many diseases ranging from asthma to cancer, but also in normal physiological conditions, such as wound healing, these findings are predicted to provide insight into the molecular mechanisms by which this lectin (and IgE) functions in these processes.