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关键词： polysaccharides   black mulberry   colitis   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： Enterovirus 71   Hand, foot, and mouth disease   RAN   IFN–STAT signaling pathway   Voxtalisib   Antiviral drugs  

摘要： Introduction Hand, foot, and mouth disease (HFMD) is a common enterovirus-induced illness primarily affecting children under 5 years of age. Enterovirus 71 (EV71) is a major causative agent associated with severe HFMD that can lead to fatal neurological complications. Despite available vaccines, no antiviral therapy with a clearly defined molecular mechanism has received approval. While most antiviral agents target viral components, host-targeting antiviral approaches remain underexplored. We first identified voxtalisib, a dual PI3K/mTOR inhibitor, through compound screening as a potential inhibitor of EV71 replication; however, the underlying mechanism remains unclear. Objectives To identify novel host-targeted antiviral candidates and to investigate the antiviral mechanism of voxtalisib against EV71 and other enteroviruses. Methods Voxtalisib was first identified as a potent anti-EV71 compound through in vitro phenotypic screening. Follow-up experiments in rhabdomyosarcoma (RD) cells were used to assess the effect of voxtalisib on EV71 replication, and proteomic analysis identified its molecular targets. Voxtalisib’s antiviral activity was also assessed against Coxsackie B viruses (CVB3, CVB4-5, and CVB4-7) and Echovirus 11 (Echo11). In vivo, suckling ICR mice were treated with voxtalisib. Survival rates, viral loads, and histopathological changes were subsequently evaluated. Results Proteomics analysis identified Ras-related nuclear protein (RAN) as a key host factor in EV71 replication. EV71 infection significantly upregulated RAN, while voxtalisib suppressed RAN. Mechanistically, RAN regulates nuclear–cytoplasmic transport of phosphorylated STAT1/2 (p-STAT1/2), affecting the interferon (IFN)-mediated antiviral response. Consequently, downregulating RAN expression enhanced the nuclear retention of p-STAT1/2 and upregulated interferon-stimulated genes expression, ultimately reducing EV71 replication. In vivo , voxtalisib improved survival, decreased viral loads,

摘要： Accumulating evidence from rodent and human studies indicates that the activity of thermogenic adipocytes positively correlates with optimal metabolic function. In this issue of the JCI, Yesian et al. uncover a paracrine signaling pathway from type 2 innate lymphoid cells to preadipocytes via IL-13 that increases beige adipogenesis through a PPAR gamma-dependent pathway. Mice with deletion of Il13ra1 demonstrated glucose dysregulation, and variants near the human IL13RA1 locus were associated with body weight and diabetic status. It is tempting to speculate that targeting IL-13 holds therapeutic potential for improving metabolic fitness in humans.

关键词： 伤口创面   新型敷料换药   改良负压技术   炎性因子   疼痛程度  

摘要： 目的探讨伤口创面应用改良负压技术结合新型敷料换药治疗的效果。方法选择该院2022年2月至2024年2月收治的伤口创面患者120例作为研究对象。随机数字表法分为两组,每组60例,包括常规敷料结合换药(常规组)、改良负压技术结合新型敷料换药(改良组)。对比两组治疗效果。结果与常规组对比,改良组伤口愈合率更高,伤口感染率、伤口溃疡率更低,伤口愈合时间、伤口渗液持续时间、住院时间更短,换药次数更少,差异有统计学意义(P<0.05);治疗1 d,两组疼痛VAS评分比较,差异无统计学意义(P>0.05),治疗3 d、7 d、14 d时改良组疼痛VAS评分低于常规组(P<0.05);治疗1 d,两组炎性因子水平比较,差异无统计学意义(P>0.05),治疗7 d改良组CRP、TNF-α、IL-8更低,与常规组比较,差异有统计学意义(P<0.05)。结论伤口创面采取改良负压技术结合新型敷料换药治疗,不仅可以更好地减轻换药期间的疼痛,而且还可缩短伤口愈合时间,减少换药次数,而且可以提高伤口愈合率,减少伤口感染或溃疡,促进患者炎性因子水平下降,可见能减轻炎症反应,缓解疼痛,更快愈合,值得应用。