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关键词： IL-33   Obesity   Spatiotemporal specificity   Expression-function paradox  

摘要： Obesity is a complex chronic metabolic disease closely associated with inflammatory responses and insulin resistance. As a member of the IL-1 cytokine family, Interleukin-33(IL-33) binds to its receptor suppression of tumorigenicity 2 (ST2) and plays a crucial role in regulating the adipose tissue immune microenvironment and maintaining metabolic homeostasis. However, its role in obesity exhibits spatiotemporal specificity and functional paradoxes. Under physiological conditions, IL-33 activates regulatory T cells (Tregs) and type 2 innate lymphoid cells (ILC2s), promoting anti-inflammatory factors secretion and adipose thermogenesis to maintain metabolic homeostasis. In obesity, despite increased IL-33 expression in obese adipose tissue, its protective effects are impaired by effector cell dysfunction, sST2-mediated neutralization, and non-classical pathway activation, collectively termed the "expression-function paradox". Notably, IL-33 exhibits tissue-specific effects in distinct organs, including adipose tissue, cardiac tissue, liver and lungs under obese conditions. This review systematically analyzes the spatiotemporal regulatory mechanisms, functional paradoxes, and therapeutic potential of IL-33 in obesity, offering new insights for targeting obesity and related metabolic disorders.

关键词： Porcine interferon-induced protein 44-like   Transmissible gastroenteritis virus   Antiviral   Type I interferon   Interferon stimulated genes  

摘要： Interferon-Induced protein 44-Like (IFI44L), a member of the interferon-stimulated genes (ISGs) family, plays a critical role in a variety of biological processes, particularly in antiviral defense and immune regulation. However, the role of human IFI44L in viral replication remains controversial. To further characterize porcine IFI44L (poIFI44L), we cloned poIFI44L for the first time and investigated its role in porcine transmissible gastroenteritis virus (TGEV) replication. The full-length poIFI44L cDNA encodes a 439-amino acid protein, containing an Nterminal TLDc domain and a C-terminal Ras-like GTPase domain. Sequence similarity to orthologs from mouse, hamster, rat, ferret, dog, rabbit, cat, horse, human, monkey, cattle and camel ranged from 48.6 % to 70.2 %. poIFI44L expression was dose-dependently upregulated in PK-15 cells by both poly (I:C) and interferon-alpha (IFN alpha-2a) treatments. Furthermore, TGEV infection significantly induced poIFI44L expression at both the mRNA and protein levels. Overexpression of poIFI44L in vitro resulted in significantly reduced TGEV N gene mRNA levels, N protein expression, and viral titers in a dose-dependent manner, whereas siRNA-mediated knockdown of poIFI44L enhanced viral replication. Mechanistically, poIFI44L upregulated IFN-beta and ISRE promoter activities and upregulated the production of IFN-beta and downstream ISGs (ISG56 and ISG60). Collectively, our data suggest that poIFI44L acts as an innate immune effector that suppresses TGEV by activating the IFN beta/ISGs signaling pathway.

关键词： Sulfasalazine   TNF alpha   Bone fracture   Osteoblast   NF-kappa B  

摘要： Fracture is a common type of traumas and alternative therapies to boost bone fracture healing is necessary. The aim of this study is to elucidate the role of sulfasalazine in bone fracture healing by using MC3T3-E1 cells in vitro and murine femoral fracture model in vivo. Western blotting, flow cytometry, RNA sequencing, Calcein AM/PI staining, Alizarin-Red-S staining, ALP activity assay, transmission electron microscope, histological staining, immunohistochemistry, immunofluorescence and Surface plasmon resonance analysis were performed in this study. Sulfasalazine failed to elicit ferroptosis in osteoblasts within acceptable dose manner while promoted osteogenic differentiation. Furthermore, sulfasalazine was identified to inhibit inflammation by declination of inflammatory biomarkers. Besides, TNF alpha was verified as a potential downstream target for sulfasalazine and the adverse effect of TNF alpha on osteogenic differentiation could be largely salvaged by sulfasalazine due to direct binding between these two molecules. RNA-seq further implied decreased transcription of genes related to NF-kappa B pathway. Murine study showed sulfasalazine promotes fracture healing as evidenced by increased bone remodeling both histologically and radiologically. Overall, sulfasalazine accelerates osteogenic differentiation and promotes bone healing by direct binding to and thus inhibiting TNF alpha, which subsequently suppresses NF-kappa B signaling. Therefore, sulfasalazine shows a promising outcome for the treatment of bone fracture.

关键词： 3D hESC-derived exosomes   hsa_circ_0076798/miR-1184/DICER1 axis   liver fibrosis   macrophages   TNF/NF-kappa B signaling pathway  

摘要： Here, we employed human embryonic stem cell spheroid (3D hESCs)-derived exosomes to assess inflammatory responses of macrophages in liver fibrosis, and found that 3D hESC-exosomes promoted the transformation of macrophages from M1 to M2 phenotype in vitro. The transplantation of 3D hESC-exosomes exhibited a notable decrease of pro-inflammatory factors, and significant increase of anti-inflammatory factors, and led to a reduction of CD86+M1 macrophages and an increase of Arg-1+M2 macrophages in the livers of treated fibrotic mice, restricting the advancement of liver fibrosis. hsa_circ_0076798, derived from 3D hESC-exosomes, acts as a molecular sponge that sequesters miR-1184, thereby mitigating miR-1184-mediated repression of DICER1 expression within macrophages. Further investigation revealed that DICER1 ultimately mitigated macrophage inflammation by deactivating TNF/NF-kappa B signaling pathway. Therefore, our findings demonstrated that 3D hESC-exosomes alleviated inflammatory responses by suppressing TNF/NF-kappa B pathway through hsa_circ_0076798/miR-1184/DICER1 axis, and offers insights into the targeted treatment of liver fibrosis via exosome-based cell-free therapy.

关键词： Duck plague virus (DPV)   Innate immunity evasion   ICP27   CGAS-STING/RIG-I signaling   IFN-beta  

摘要： Duck plague virus (DPV), an alphaherpesvirus causing severe economic losses in global waterfowl industries, adopts sophisticated strategies to subvert host antiviral immunity. Here, we identify DPV ICP27 as a pivotal immune evasion protein that concurrently inhibits both DNA (cGAS-STING) and RNA (RIG-I/MDA5-MAVS) innate immune sensing pathways-a novel function unreported in avian herpesviruses. Through co-transfection and infection assays in duck embryo fibroblasts (DEFs), we demonstrate that ICP27 suppresses key immune sensors' transcriptional and protein expression levels (STING, RIG-I) and the transcription factor IRF7. Coimmunoprecipitation confirms ICP27 binds to IRF7, impairing interferon regulatory functions, impairing interferon regulatory functions. Crucially, infection with ICP27-knockout DPV (DPV-Delta ICP27) significantly enhances IFN-beta, IL-6, Mx, and OASL expression compared to wild-type virus. Phylogenetic analyses reveal conserved yet species-specific functional divergence of ICP27 across herpesviruses. Our findings identify a unique "multi-target cooperative suppression" mechanism employed by DPV, which enhances our understanding of avian herpesviral immune evasion and offers potential targets for developing novel antiviral strategies.

关键词： Zebrafish   iPSc cardiomyocytes   Myosin heavy chain   Sarcomeres   Homeostasis   Filament assembly  

摘要： The SMYD family comprises a distinct class of lysine methyltransferases (KMTases) that methylate both histone and non-histone proteins. Among its five members (SMYD1-5), SMYD1 has been identified as a cardiac and skeletal muscle-specific KMTase that interacts with Myosin, in coordination with Unc45b and Hsp90a, to regulate thick filament assembly. However, the precise mechanism by which SMYD1 orchestrates Myosin assembly remains largely unknown. Here, we demonstrate that SMYD1 physically associates with the N-terminal region of several myosin heavy chain (MyHC) isoforms and specifically catalyzes the mono-methylation of MyHC at lysine 35 (K35). Methylated MyHC is correctly incorporated into sarcomeres, whereas unmethylated MyHC in Smyd1-deficient zebrafish undergoes degradation via the ubiquitin-proteasome system (UPS), leading to defective thick filament assembly. Although UPS inhibition with MG132 restores Myosin levels in Smyd1-deficient zebrafish embryos, proper thick filament assembly remains impaired due to the absence of K35 MyHC mono-methylation. Similar to zebrafish striated muscle cells, SMYD1-mediated MyHC methylation is essential for thick filament assembly but also homeostasis in human cardiomyocytes, indicating a conserved cross-species mechanism of Myosin regulation, first described nearly 40 years ago. Further research is now required to explore the therapeutic potential of targeting this pathway in cardiomyopathies and skeletal muscle disorders.

关键词： gut microbiota   cytokine   claudin-3   lipopolysaccaride-binding protein   intercellular adhesion molecule 1   AST   Aspartate aminotransferase   ALT   Alanine transaminase   APRi   AST-to-platelet ratio index   BA   Biliary atresia   GGT   Gamma-glutamyl transferase   ICAM-1   Intercellular adhesion molecule 1   IFABP   Intestinal fatty acid binding protein   IL   Interleukin   IFNγ   Interferon gamma   LT   Liver transplantation   LPS   Lipopolysaccharide   LSM   Liver Stiffness Measurement   LBP   Lipopolysaccharide binding protein   TNFα   Tumor necrosis factor alpha   TB   Total bilirubin   VCAM-1   Vascular cell adhesion molecule 1  

摘要： Objective: To explore the relationship among bacterial translocation, intestinal barrier integrity, and systemic inflammation in early biliary atresia (BA). Study design: Newly diagnosed infants with BA were assessed longitudinally before as well as 6, 12, and 24 weeks after undergoing Kasai portoenterostomy. Plasma immune marker measurement included interleukin (IL)-2, interferon-gamma (IFN gamma), IL-4, IL-10, tumor necrosis factor alpha, IL-6, IL-8, IL-1 beta, IL-17, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Bacterial translocation (lipopolysaccharide binding protein [LBP];D-lactate), intestinal barrier (claudin-3;intestinal fatty acid binding protein [IFABP], fecal calprotectin) biomarkers, and fecal microbiota genus abundance were analyzed. Results: Fifty-five infants were included, of whom 60% cleared their jaundice. Early post-Kasai, upregulation of plasma adhesion molecules and pro-inflammatory cytokines were associated with poorer jaundice clearance and liver fibrosis and correlated with jaundice severity. Elevated claudin-3 early post-Kasai was associated with poor jaundice clearance [OR 1.02 (1.00, 1.04);P = .02] and jaundice severity [P < .01]. On multivariable analysis, early ICAM-1 elevation (OR 1.008 [1.002, 1.014];P = .01) and claudin-3 (OR 1.038 [1.009, 1.068];P = .02), represented independent prognostic markers for persistent jaundice. Increased longitudinal trends of LBP (OR 0.79 [0.71, 0.89];P < .01) and IFABP (OR <0.01 [2.4E-43, 0.24];P = .04) were associated with poor jaundice clearance. LBP positively correlated with pro-inflammatory-cytokines (IL-6, P < .01: TNF alpha, P < .01) and ICAM-1 (P < .01) early post-Kasai. Fecal calprotectin positively correlated with jaundice severity (P < .01) by 24 weeks post-Kasai. No correlation between fecal microbiota abundance and bacterial translocation/intestinal integrity markers was demonstrated. Conclusions: Bacterial translocation may be linked to post-K

关键词： CRP   Daily rhythm   Horses   IL-6  

摘要： Background: Homeostasis and inflammation are two opposing physiological processes that are driven by the circadian clock. Aims/objectives: The study aim was to investigate the biological rhythm of the C-reactive protein (CRP) and Interleukin-6 (IL-6) in horses. Methods: Eight clinically healthy Italian saddle gelding horses, housed in individual boxes and subjected to a natural 12/12 L/D cycle, were enrolled. Blood samples were performed every 4 hours over a 48-hour period. Results: A positive correlation was found between CRP and IL-6 on both days of monitoring. Both parameters showed a daily rhythm;CRP acrophase was in the middle of the scotophase, IL-6 acrophase at the beginning of the light phase, and both parameters had a high percentage of robustness (>75%). Conclusion: This preliminary information improves the knowledge about the daily rhythm and possible correlation of some inflammatory biomarkers in horses. Further studies are necessary to investigate how different environmental conditions, management, and physical exercise might influence this rhythmicity.

关键词： 白介素-6   C反应蛋白   轮状病毒   诺如病毒感染   动态变化  

摘要： 目的 探究白细胞介素-6(IL-6)、C反应蛋白(CRP)、降钙素原(PCT)在轮状病毒与诺如病毒感染诊断/鉴别与感染进展评估中的意义.方法 研究年限范围为 2024 年 8 月至 2025 年 3 月期间,选取 219 例江门市妇幼保健院收治的疑似感染患儿进行研究,均实施IL-6、CRP、PCT检测,以病毒核酸检测(PCR)结果为金标准,分析各个方案阳性检出率、诊断效能、不同病毒类型者检测结果及不同时期波动.结果 PCR检测真阳性 100 例、真阴性 119 例,以PCR结果为金标准,IL-6 检出真阳性 89 例、真阴性 109 例;CRP检出真阳性91例、真阴性111例;PCT检出真阳性90例、真阴性110例;IL-6+CRP+PCT检出真阳性98例、真阴性118例.IL-6+CRP+PCT特异度、准确率、与金标准一致性高于单一检查,且诺如病毒组IL-6、CRP、PCT较之轮状病毒组更高(P＜0.05);潜伏期、恢复期IL-6、CRP、PCT低于急性期(P＜0.05).结论 IL-6、CRP、PCT在轮状病毒与诺如病毒感染水平变化存在明显波动,且随着病情进展数据可发生波动,可根据具体检测结果对病情进行判断,从而采取合理干预方案.

关键词： Chronic obstructive pulmonary disease   Interleukin-36   Airway inflammation   Emphysema   Skeletal muscle dysfunction  

摘要： Chronic inflammation is a crucial driver in the development of chronic obstructive pulmonary disease (COPD) and its comorbidities, such as skeletal muscle dysfunction. Heightened IL-36 expression in the lung and systemic circulation has been observed in patients with COPD, but the potential role of IL-36 in COPD still needs further exploration. Herein, we established a COPD model through long-term cigarette smoke (CS) exposure in mice with or without IL-36R deletion. Elevated IL-36 cytokines were observed in the lung and peripheral blood of CS-exposed wild-type mice. IL-36R gene deficiency attenuated CS-induced lung parenchymal destruction and airway inflammation, as evidenced by decreased secretion of inflammatory mediators, such as IL-6, IL-1 beta, TNF-alpha and MMP9, and a diminished Th1/Tc1-and Tfh-biased immune response. In addition, skeletal muscle dysfunction was alleviated in CS-exposed mice by IL-36R deletion. Further investigations indicated that CS treatment induced the expression of IL-36 cytokines and IL-36R in C2C12 myotubes and skeletal muscles, and that IL-36 cytokines could upregulate FBXO32 and TRIM63 expression by activating NF-kappa B p65 pathway, thereby leading to skeletal muscle atrophy in an endocrine and autocrine/paracrine manner. Our findings provide evidence for a critical role of the IL-36/IL-36R signaling in the pathogenesis of CS-induced COPD and comorbid skeletal muscle dysfunction.