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关键词： Hypobaric hypoxia   HAPE   NKT cells   IL-10   curcumin  

摘要： Background: There are environment-dependent pro-inflammatory and anti-inflammatory pathways during exposure to high altitudes. Although inhibiting the inflammatory pathway can alleviate high altitude pulmonary edema (HAPE), it is currently unclear whether inflammation is the cause of edema or the result of edema in HAPE-afflicted patients. Natural killer T (NKT) cells are a subset of T cells that play an important role in a variety of lung diseases. However, its specific role in HAPE remains unclear. Methods: HAPE rat model was established under hypobaric hypoxia condition. To investigate the role of NKT cells in HAPE, phenotypic and functional changes of NKT cells and their subpopulations were analyzed by flow cytometry. To further investigate the effect of TNF-alpha on NKT cells, rats were given intraperitoneal injection of TNF-alpha, and then, NKT cells were characterized by flow cytometry. Subsequently, the levels of TNF-alpha in the lungs and spleens of rats were detected by ELISA, and HAPE rats were treated with curcumin. Results: Compared with normal control, the ratio of TNF-alpha and IL-10 secreted by lung NKT cells was decreased in HAPE rats induced by hypoxia. Further analysis showed that the mean fluorescence intensity (MFI) of TNF-alpha in NKT cells did not change significantly, but the MFI of IL-10 increased significantly. Moreover, the MFI of IL-10 produced by TNF-alpha-treated rat lung NKT cells was higher, which was completely different from spleen NKT cells. ELISA experiments indicated that TNF-alpha was enriched in the lung tissue of rats regardless of hypoxia, and the level of TNF-alpha in lung tissue was upregulated after hypoxia. Furthermore, when HAPE rats were treated with curcumin, the MFI of IL-10 in the NKT cell subsets decreased. Conclusions: NKT cells produce high levels of IL-10, which inhibits the production of lung inflammation in HAPE rats. With the increase of TNF-alpha level, the inhibitory effect of lung NKT cells on inflammation

关键词： Adult-onset Still's disease   Mass cytometry   Tocilizumab  

摘要： BackgroundEarly administration of IL-6R blockade is effective in adult-onset Still's disease (AOSD), but the underlying immune alterations during combined immunotherapy remain *** employed high-dimensional single-cell mass cytometry and an unbiased bioinformatics pipeline to characterize the immune landscape in treatment-na & iuml;ve AOSD patients, stable AOSD patients after 24 weeks of IL-6R blockade plus methotrexate and prednisone, and matched healthy controls. Cytokine profiling was conducted using a high-throughput cytometric bead array, and potential regulatory networks were identified using the PerformanceAnalytics package. Validation was performed via flow cytometry and mRNA *** identified 22 peripheral immune cell populations and characterized their composition and phenotypic markers. Treatment-na & iuml;ve AOSD patients exhibited significant depletion of CD4+ T cells and B cells, along with excessive activation of CD8+ T cells and a previously unreported CD45+CD3-CD19-CD10-CD66a+ population, findings that were validated in an independent AOSD cohort. mRNA sequencing revealed the proinflammatory role of CD8+ T cells. Notably, these dysregulated immune profiles were markedly restored following immunotherapy. IL-18, IL-21, and IFN-gamma demonstrated strong associations with adaptive immune cells and AOSD clinical *** IL-6R blockade effectively modulates immune dysregulation in refractory AOSD, reversing key pathological immune alterations and highlighting its therapeutic potential.

关键词： polysaccharides   black mulberry   colitis   italic>Weissella   TNF   tight junctionprotein  

摘要： Colitis is characterized by immune dysregulation and gut microbiota imbalance. This study investigates the therapeutic effects of polysaccharides from black mulberry (PBM) on dextran sulfate sodium-induced colitis in mice. PBM administration significantly alleviated colitis symptoms, including body weight loss, histological damage, and inflammation, while enhancing antioxidant capacity and strengthening tight junction protein expression. PBM modulated gut microbiota composition, notably increasing Weissella spp., which correlated with elevated short-chain fatty acids (SCFAs) and decreased pro-inflammatory markers. Colonic RNA sequencing revealed the role of PBM in attenuating colitis via the TNF-alpha/NF-kappa B/ICAM-1 signaling pathway. Fecal microbiota transplantation (FMT) from PBM-treated mice confirmed that microbiota modulation from PBM contributed to these therapeutic effects. These findings suggest PBM as a natural therapeutic agent for colitis, offering a multifaceted approach to restoring gut homeostasis through microbiota modulation and inflammatory pathway regulation. This study provides new insights into dietary polysaccharides as potential adjunctive therapies for colitis.

关键词： Multiple sclerosis   IFNG rs2069727 T/C   Interferon-gamma   MicroRNA   Biomarker  

摘要： Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder, with relapsing-remitting MS (RRMS) being the most common subtype. Interferon-gamma (IFN-gamma) plays a dual role in MS pathogenesis. MicroRNAs (miRNAs) have emerged as potential diagnostic biomarkers. This study examined the effect of relative expression of hsa-miR-24-3p and hsa-miR-181d-3p, plasma IFN-gamma levels, and the IFNG rs2069727 T/C variant on MS risk, evaluating their interrelationships and diagnostic potential. This case-control study comprised two overlapping groups-a genetic polymorphism group (330 RRMS, 330 healthy controls (HCs)) and a miRNA group (25 glatiramer acetate (GA)-treated RRMS patients, 25 treatment-na & iuml;ve RRMS patients, and 25 HCs)- collected at the Ankara Bilkent City Hospital Neurology Polyclinic. The IFNG rs2069727 T/C variant did not display a statistically significant disparity between RRMS patients and HCs. Significantly elevated hsa-miR-24-3p and hsa-miR-181d-3p relative expression levels were observed in GA-treated and treatment-na & iuml;ve RRMS patients compared to HCs. Conversely, age-adjusted plasma IFN-gamma concentrations were markedly lower in GA-treated and treatment-na & iuml;ve RRMS patients versus HCs. Individuals with low plasma IFN-gamma levels (<= 1.311 pg/mL) demonstrated significantly elevated hsa-miR-24-3p relative expression compared to the high IFN-gamma group (> 1.311 pg/mL). Conversely, subjects with low hsa-miR-181d-3p levels (<= 2.90) exhibited significantly higher plasma IFN-gamma concentrations relative to those with high hsa-miR-181d-3p levels (> 2.90). In the GA-treated group, EDSS negatively correlated with age-adjusted plasma IFN-gamma. This study identified age-adjusted plasma IFN-gamma, hsa-miR-24-3p, and hsa-miR-181d-3p expression as potential blood-based biomarkers for RRMS diagnosis and analyzed them alongside disability scores. The miRNAs in this study can be further evaluated as prospective therapeutic targets.

关键词： coronary thrombus   NETs   STEMI   inflammation   IL-6R   PAD4  

摘要： Inflammation contributes to myocardial injury in ST-elevation myocardial infarction (STEMI). Interleukin-6 receptor (IL-6R) inhibition has been shown to mitigate myocardial injury and reduce levels of the prothrombotic and inflammatory mediator, neutrophil extracellular traps (NETs). The enzyme peptidylarginine deiminase 4 (PAD4) is central in NET formation. We hypothesized that PAD4 links IL-6R activation and NET formation. Methods: We conducted thrombus aspiration and peripheral blood sampling in 33 STEMI patients. In thrombi and leukocytes, we quantified the mRNA of IL-6, IL-6R, and PAD4. In peripheral blood, the protein levels of IL-6, IL-6R, PAD4, dsDNA, H3Cit, MPO-DNA, and troponin T were quantified. Results: In thrombi and circulating leukocytes, PAD4 mRNA was associated with IL-6R mRNA (thrombi: beta = 0.34, 95% CI [0.16-0.53], p = 0.001, circulating leukocytes: beta = 0.92, 95% CI [0.07-1.77], p = 0.036). There were no correlations between PAD4 and IL-6 in thrombi and leukocytes. The protein levels of IL-6R were associated with the NET marker H3Cit (rs = 0.40, p = 0.02). In thrombi, PAD4 mRNA was associated with high levels of troponin T (beta = 1.15 95% CI [0.27-2.04], p = 0.013). Conclusion: We demonstrate an association between PAD4, IL-6R, and troponin release in STEMI patients. Our findings indicate a PAD4-mediated connection between IL-6R and NET formation and highlight PAD4 as a potential treatment target for mitigating inflammation and myocardial injury in STEMI.

关键词： HLA-II   MHC-II   Antibody-repertoires   B-cells   GWAS   PhIP-Seq  

摘要： BackgroundHuman leukocyte antigen class II (HLA-II) genes are highly polymorphic affecting the specificity of human antibody responses, as presentation of processed antigen peptides by HLA-II on B cells is essential for T helper cell dependent affinity maturation and class *** combination of high-throughput immunoassays and genome-wide association studies has recently revealed strong associations between HLA-II variants and antibody responses against specific antigens. However, factors underlying these associations remain incompletely *** leukocyte antigen class II (HLA-II) genes are highly polymorphic affecting the specificity of human antibody responses, as presentation of processed antigen peptides by HLA-II on B cells is essential for T helper cell dependent affinity maturation and class *** combination of high-throughput immunoassays and genome-wide association studies has recently revealed strong associations between HLA-II variants and antibody responses against specific antigens. However, factors underlying these associations remain incompletely ***, we have leveraged paired data sets of SNP arrays and functional antibody epitope repertoires against 344,000 peptide antigens in 1940 individuals to mine for key determinants linking genetics and antibody *** show that secreted proteins and antigens presented in small modules (i.e., viruses) are significantly more frequently associated with HLA-II alleles, than membrane bound or intracellular proteins. This data suggests a model in which antibody responses against separate antigen units composed of single or few proteins dominate HLA-II associations. In contrast, the presence of manifold intracellular or membrane proteins (peptides of which could be bound by different HLA-II alleles) on bacterial cells dilutes potential associations to antibody ***, genetic associations to antibody specificities are shaped

关键词： Ankylosing spondylitis   IL-33   SST-2   Cardiovascular disease   Carotid intima media thickness  

摘要： BackgroundCardiovascular disease is the main cause of death in patients with ankylosing spondylitis (AS). Previous studies showed high serum levels of IL- 33 in AS patients and suggested that it may play a role in disease development. However, the possible role of IL- 33/sST- 2 in atherosclerosis in AS has not been *** assess serum levels of IL- 33 and sST- 2 and to assess their association with carotid intima-media thickness (CIMT) and disease activity in a group of Egyptian patients with *** levels of IL- 33 and sST- 2 were statistically higher in AS patients compared to controls (median, 451.75 vs 37.42, p = 0.000) and (median, 5.71 vs 0.74, p = 0.000) respectively. IL- 33 and sST- 2 levels positively correlated with Bath Ankylosing Spondylitis Disease Activity Index (r = 0.445, p = 0.004) and (r = 0.421, p = 0.007) respectively, and Ankylosing Spondylitis Disease Activity Score with CRP (r = 0.684, p = 0.000) and (r = 0.452, p = 0.003) respectively. There was a positive correlation between serum IL- 33/sST- 2 and *** high serum levels of IL- 33 and sST- 2 in AS patients and their positive correlation with CIMT and AS disease activity suggest that IL- 33/ST2 axis-induced inflammation may be a major factor in the development of cardiovascular disease in AS patients.

关键词： Anti-inflammatory   Human health   Network Pharmacology   Rubiaceae   UPLC-Q-TOF-MS   Sore throat relief  

摘要： Psychotria rubra Herbal Tea (PRHT) is a traditional Chinese folk medicine used to treat in-flammation induced by respiratory infections. Its specific mechanisms of action, however, remain unclear. The study combined ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), network pharmacology, and in vitro cell experiments to systematically analyze the chemical composition and validate the biological activity of PRHT. Protein-protein interaction (PPI) network analysis and molecular docking were used to identify key targets and mechanisms. PRHT was found to contain 128 active compounds, including alkaloids, amino acids and their derivatives, and flavonoids. Key targets such as STAT3, IL-6, and TP53 were identified through PPI network analysis. PRHT exhibited significant anti-inflammatory effects by modulating the STAT3/IL-6/TNF-alpha signaling pathway. Experimental results demonstrated that PRHT inhibited the release of inflammatory cytokines in a dose-dependent manner. Molecular docking confirmed strong interactions between PRHT components and core targets. The study reveals that PRHT exerts anti-inflammatory effects by regulating the STAT3/IL-6/TNF-alpha signaling pathway, contributing to inflammation balance and tis-sue repair. These findings provide scientific evidence for the development of PRHT as a functional anti-inflammatory agent and offer new insights into treatment strategies for respiratory infections.

摘要： Donor-specific T cell responses, particularly against human leukocyte antigen (HLA)-DQ antigens, are critical in transplant immunology as they influence graft survival and rejection. This study investigated HLA-DQ-specific CD4 T cell responses in naive individuals using HLA-DQ monomers, representing common donor HLA-DQ antigens (DQ2.5, DQ5, DQ6, DQ8), as defined alloantigen sources to enrich and detect HLA-DQ-specific T cells. Using a repeated stimulation protocol with HLA-DQ monomers, we achieved an enrichment of HLA-DQ-specific CD4 T cells, evidenced by proliferation and activation marker upregulation. Additionally, epitope prediction identified 15-mer HLA-DQ peptides capable of binding to self-HLA-DRB1 alleles. TCR sequencing demonstrated an enriched, oligoclonal repertoire of HLA-DQ-specific CD4 T cells post-stimulation, with specific TCR clonotypes expanding in response to HLA-DQ monomer stimulation. Together, our study presents an method for enriching HLA-DQ-specific CD4 T cells using HLA-DQ monomers as an alloantigen source, thereby improving the detection of alloreactive, donor-specific T cells in naive individuals with the potential to mediate immune responses, including graft rejection and donor-specific antibody (DSA) production.

关键词： span>Enterovirus 71Hand, foot, and mouth diseaseRANIFN–STAT signaling pathwayVoxtalisibAntiviral drugs