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Benign prostatic hyperplasia is a common public health problem in aging men across the globe. Diarylpropionitrile, a selective estrogen receptor-beta agonist, favorably regulates cell proliferation and inflammation, two major hallmarks of benign prostatic hyperplasia pathology.This study aimed to explore the mitigative impact of diarylpropionitrile on testosterone-induced benign prostatic hyperplasia in rats.Forty male rats were randomly divided into four groups ( Show less

Interleukin-27 (IL-27) in the pleural fluid has gained significant attention as a diagnostic biomarker for tuberculous pleural effusion (TPE); however, considerable variability exists across available studies. This systematic review and meta-analysis aimed to determine the diagnostic accuracy of IL-27 in identifying TPE. In addition, we also compared the diagnostic accuracy of IL-27 and adenosine deaminase (ADA) with a head-to-head meta-analysis. We searched the PubMed and Web of Science databases to identify diagnostic test accuracy studies evaluating the accuracy of IL-27 for diagnosing TPE. The last search date was September 2025. We extracted data from the eligible studies and constructed a two-by-two table with true positives (TP), false positives (FP), true negatives (FN), and false negatives (FN). The QUADAS-2 tool was used to assess the quality of eligible studies. A bivariate model was applied to pool sensitivity and specificity, and a summary receiver operating characteristic (sROC) curve with the area under the curve (AUC) was generated to estimate the overall diagnostic accuracy of IL-27 and ADA. A Deeks funnel plot asymmetry test was used to evaluate publication bias. Nine studies encompassing ten cohorts were included, involving 1573 patients (429 with TPE and 1144 with non-TPE). The reported AUCs for IL-27 ranged from approximately 0.73 to 0.99 across eligible studies. The pooled sensitivity and specificity were 0.94 (95% CI, 0.83-0.98) and 0.96 (95% CI, 0.89-0.98), respectively. The AUC for sROC was 0.99 (95% CI, 0.97-0.99). The pooled positive likelihood ratio was 21.97 (95% CI, 7.95-60.69), the negative likelihood ratio was 0.07 (95% CI, 0.02-0.18), and the diagnostic odds ratio (DOR) was 329 (95% CI, 72-1506). Significant heterogeneity was observed in both sensitivity (I IL-27 is a promising diagnostic marker for TPE, and its diagnostic accuracy is comparable to that of ADA. IL-27 should be used as a complementary diagnostic marker to ADA for TPE. Show less

Pelvic radiation therapy is an essential treatment for several pelvic malignancies, but it can lead to radiation cystitis (RC), a severe progressive inflammatory bladder disorder lacking effective diagnosis and therapeutic options. RC evolves through acute, latent, and chronic phases, ultimately resulting in bladder fibrosis, vascular damage, and hematuria. Here, we characterize the molecular and immunological features associated with RC progression using a preclinical mouse model. Building on a prior analysis of the acute and chronic phases, we examined the previously unanalyzed latent phase and integrated transcriptomics, immune cell profiling, inflammatory protein measurements, and bladder function assessments across all stages. Acute radiation injury was marked by the strong activation of apoptotic pathways, whereas latent and chronic phases were dominated by inflammatory signaling with distinct cytokine and chemokine signatures. The persistent upregulation of Cdkn1a (P21) was consistent with sustained senescence-associated signaling, while reductions in IL-27 and shifts in the granulocyte-lymphocyte-enriched immune population during the latent phase were consistent with altered immune regulatory states. At chronic stages, increased SASP-associated proteins and matrix remodeling mediators coincided with bladder functional decline. Together, these findings support a model in which radiation-induced senescence, coupled with immune dysregulation during the latent phase, are coordinated features accompanying inflammation, tissue remodeling, and bladder dysfunction in RC. Show less

Patients with pulmonary arterial hypertension (PAH) experience long diagnostic delays, high functional class at diagnosis and poor prognosis. We aimed to study the differentiative and predictive value of 90 inflammatory and immunomodulatory related proteins in idiopathic and hereditary PAH (IPAH/HPAH) and systemic sclerosis-associated PAH (SSc-APAH). Cohort 1 comprised patients with SSc-APAH ( Show less

Visceral leishmaniasis (VL) is a neglected tropical disease with high mortality and limited treatment options. Amphotericin B (AmB) remains the most effective drug but is constrained by dose-dependent toxicity. Immunotherapy using parasite-derived components may potentiate host defenses and host protective responses and attenuate drug-induced cytotoxicity. This study investigated the therapeutic efficacy and immune response-modulating mechanism of AmB in combination with ultradiluted Leishmania antigen (udLA) in a murine model of VL. BALB/c mice were experimentally infected with L.donovani promastigotes and subsequently treated with AmB, udLA, or their combination. Parasite burden in hepatic and splenic tissues was quantified via Leishman-Donovan Units and quantitative PCR. Cellular immune responses were characterized by flow cytometric analysis of CD4 All therapeutic regimens significantly reduced parasite load relative to untreated controls, with the AmB+udLA combination achieving up to 96% reduction. Combination therapy elicited pronounced expansion of CD4 Co-administration of AmB with ultradiluted Leishmania antigen markedly enhances antileishmanial efficacy through potentiation of Th1-biased immune response and activation of macrophage effector mechanisms, while concurrently minimizing drug induced toxicity. These findings underscore the potential of udLA as a rational safer strategy for the management of VL. Show less

T Regulatory T cells (Tregs) from patients with relapsing-remitting multiple sclerosis (RRMS) exhibit impaired suppressive function, yet the underlying molecular mechanisms remain elusive. Single-cell RNA sequencing (scRNAseq) of Show less

Coronary artery disease (CAD) is an immune-mediated disorder driven by dysregulated T cell responses. Interleukin-27 (IL-27) has immunoregulatory properties, but its role in CAD remains unclear. This study is the first to investigate the effects of IL-27 on CD4⁺LAP⁺ T cells in CAD and to explore its interaction with interleukin-2 (IL-2) in modulating immune imbalance. CAD severity was quantified by the Gensini score. Plasma IL-27 and oxidized low-density lipoprotein (ox-LDL) were measured by ELISA. Flow cytometry assessed CD4⁺ T cell subsets, while qRT-PCR and Western blot evaluated lineage-specific transcription factors. IL-27 levels were elevated in acute coronary syndrome and correlated with ox-LDL and Gensini scores. Patients with severe CAD showed a Th1/Th17-dominant profile and reductions in Th2, CD4⁺LAP⁺, and Tregs. In vitro, IL-27 promoted Th1 differentiation via T-bet/IFN-γ upregulation and suppressed Th2, Th17, and regulatory subsets, counteracting IL-2-induced expansion of Tregs and CD4⁺LAP⁺ cells. These effects were dose dependent and favored pro-inflammatory responses. IL-27 drives immune imbalance in CAD by reinforcing Th1 polarization and antagonizing IL-2-mediated regulation. Beyond mechanistic insights, these findings identify IL-27 as a potential biomarker for disease severity and a candidate therapeutic target in CAD. Show less

DNA methylation plays a pivotal role in the pathogenesis of Acute Lymphocytic Leukemia (ALL), a hematological malignancy marked by abnormal cellular behavior and immune dysregulation. This study aimed to investigate how alterations in DNA methylation affect lysosmal function in pediatric ALL. A total of 50 blood samples were collected from children diagnosed with ALL and analyzed for biochemical markers associated with the disease. Expression levels of key DNA methylation regulators, including DNA methyltransferase 1 (DNMT1) and DNMT3, were evaluated and compared with those from healthy controls. In addition, pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-27 (IL-27), and tumor necrosis factor-alpha (TNF-α), were monitored over a six-day period prior to treatment initiation. The study also assessed the expression of lysosome-associated membrane proteins, LAMP1 and LAMP2, which are essential for lysosomal function and the degradation of autophagosomes. To determine the DNA methylation status of the promoter regions of these genes, genomic DNA underwent sodium bisulfite treatment and digestion with methylation-sensitive and methylation-dependent restriction enzymes, followed by amplification with gene-specific primers. Our results revealed a significant upregulation of DNMT1 and DNMT3 in ALL samples, along with a marked downregulation of TET1 gene expression, which is responsible for DNA demethylation. This suggests that disrupted DNA methylation dynamics may contribute to the pathogenesis of the disease. Furthermore, methylation levels within the CpG islands of the LAMP1 and LAMP2 promoter regions were substantially elevated, showing more than a seven-fold increase in ALL samples compared to healthy control blood samples. In ALL samples, the expression levels of LAMP1 and LAMP2 were significantly reduced, may due to promoter region hypermethylation, which contributes to lysosomal dysfunction. In parallel, the expression of autophagy-related genes such as ATG5 and LC3B, markers of autophagy initiation and maturation, respectively, was markedly increased, suggesting an accumulation of autophagosomes that depend on functional lysosomes for complete degradation. Additionally, elevated levels of pro-inflammatory cytokines IL-6, IL-27, and TNF-α were consistently observed in ALL patients, indicating heightened immune activation that may drive disease progression. Collectively, these findings underscore the pivotal role of DNA methylation in disrupting lysosomal function, leading to autophagosome accumulation and impaired recycling of cytoplasmic components. Show less

Despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) experience persistent inflammation, immune dysfunction, and premature onset of cardiovascular and aging-related comorbidities. To define the underlying mechanisms, we performed longitudinal transcriptomic profiling in peripheral blood mononuclear cells (PBMCs) from a cohort of simian immunodeficiency virus (SIV)-infected rhesus macaques spanning four key stages: pre-infection, acute infection, short-term ART, and long-term ART. Bulk RNA sequencing revealed dynamic immune remodeling across infection and treatment. Acute SIV infection induced robust antiviral and inflammatory programs, with upregulation of interferon-stimulated genes (ISGs), IL-27, JAK/STAT, and NF-κB signaling, coupled with suppression of T- and B-cell activation pathways. Short-term ART effectively reversed these transcriptional perturbations, restoring adaptive immune gene expression and reducing innate antiviral responses to near-baseline levels. In contrast, chronic SIV infection on long-term ART maintained viral suppression but was characterized by reactivation of innate immune pathways, including TLR2/TLR4/MYD88, NF-κB, and inflammasome (NLRP3/or NLRP12, caspase-1) signaling, along with sustained macrophage activation, platelet/coagulation signaling, and senescence-associated secretory phenotype. Protein analyses confirmed persistent CASPASE-1 and NF-κB activation in spleen tissue. Pathologic evaluation of a carotid artery from an SIV-infected, long-term ART-treated macaque revealed macrophage-rich plaques with p21 Show less

Many inflammatory stimuli can induce progenitor cells in the bone marrow to produce increased numbers of myeloid cells as part of the process of emergency myelopoiesis. These events are associated with trained immunity and have long-term impacts on hematopoietic stem and progenitor cell (HSPC) development but can also compromise their function. While many cytokines support emergency myelopoiesis, less is known about the mechanisms that temper these events. When mice that lack the cytokine IL-27 were infected with Show less

Oxymatrine is an alkaloid with the property of immunomodulation. Recent studies have demonstrated that oxymatrine inhibits experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by promoting the production of interferon-β (IFN-β). However, the mechanism through which oxymatrine regulates the production of IFN-β remains unclear. The aim of this study was to investigate the pharmacological effects and related molecular mechanisms of oxymatrine in the treatment of EAE through in vivo and in vitro experiments. Oxymatrine alleviated neurological dysfunction, demyelination, and inflammation in EAE mice. It reduced microglia/macrophage infiltration and polarization, lowered pro-inflammatory cytokine levels (iNOS, TNF-α), and enhanced the expression of IL-10 and IL-27. Additionally, oxymatrine upregulated the STING/TBK1/IRF3 signaling pathway in EAE mice, promoting IFN-β production by microglia. Similarly, in LPS-induced BV2 cells, oxymatrine suppressed inflammatory factors and activated the STING/TBK1/IRF3 pathway to enhance IFN-β production. Notably, treatment with the STING inhibitor, C176, reversed these effects in both EAE mice and LPS-induced BV2 cells, confirming the pathway's critical role in the mechanism of oxymatrine therapy. Oxymatrine promotes IFN-β production in microglia by upregulating the STING/TBK1/IRF3 signaling pathway, thereby alleviating the neurological dysfunction of EAE and reducing pathological and inflammatory events. This study identifies a novel anti-EAE mechanism of oxymatrine: promoting IFN-β production in microglia by activating the STING/TBK1/IRF3 pathway. However, it lacks clinical sample verification. If validated later, oxymatrine may provide a more economical, convenient endogenous IFN-β induction regimen for MS patients. Show less

Sow colostrum is rich in lactoferrin (LF), which can be orally administered to protect piglets from porcine epidemic diarrhea virus (PEDV) infection, thereby reducing piglet mortality. Previous study has shown that sows fed with recombinant B. subtilis expressing 4,4-diaponeurosporene (B.S-Dia) have significantly higher LF levels in their colostrum compared to sows fed with B. subtilis. This suggests that 4,4-diaponeurosporene (DNP) produced by B.S-Dia may influence LF content in sow colostrum. In this study, we first extracted DNP expressed by the recombinant probiotic using acetone-hexane extraction. Flow cytometry, RT-qPCR, and ELISA analyses demonstrated that DNP promoted dendritic cell (DCs) maturation and increased the expression of IL-1β and IL-27. We then established a method for isolating neutrophils from sow colostrum and set up a co-culture system of neutrophils and DCs to investigate factors regulating LF secretion. The results indicated that DCs secretions enhanced LF expression in neutrophils. Finally, the application of IL-27 inhibitors confirmed that IL-27 produced by DCs upregulates LF secretion in neutrophils. These findings elucidate the mechanism by which DNP promotes LF production in colostrum and provide a theoretical foundation for using B.S-Dia to prevent and control PEDV infection in piglets. Show less

Congenital viral infections can have severe consequences for pregnancy and fetal outcomes. Remarkably, the fetal-derived placenta serves as a robust barrier to infection through meticulous regulation by immune effectors and cytokines. Yet, the regulatory roles of many cytokines remain undefined at the maternal-fetal interface, including Interleukin-27 (IL-27). Here, we show that trophoblast organoids derived from human placentas constitutively express both IL-27 and its receptor, and restrict Zika virus infection through IL-27 signaling. Through bulk RNA-sequencing of trophoblast organoids in the absence and presence of IL-27 signaling, we demonstrate IL-27-mediated upregulation of antiviral genes. Finally, we show that IL-27 signaling is critical to restricting placental viral burdens and protecting against pathologic fetal outcomes during murine congenital Zika virus infection. In this work, we demonstrate a novel role for IL-27 in the placenta and establish IL-27 as an innate antiviral defense at the maternal-fetal interface during congenital viral infection. Show less

Liver diseases, ranging from chronic liver disease (CLD) to acute liver injury (ALI), pose significant global health challenges. Metabolic dysfunction and inflammatory disorders are key to the progression of both CLD and ALI, suggesting that dual-targeting of metabolism and immune response may lead to better clinical performance for patients with liver disease. Interleukin-27 (IL-27) is a classic cytokine known for its immune-modulating role, with many ongoing clinical trials in the context of anti-tumoral therapy and inflammatory bowel disease. Our previous studies have revealed an unexpected role of IL-27 in promoting adipocyte thermogenesis and ameliorating role in systemic metabolism. This review outlines the involvement of the IL-27/IL-27R signaling pathway in hepatic metabolism and immunity, highlighting its potential as a therapeutic target for both CLD and ALI. Meanwhile, when serum IL-27 displays a disease-specific change in dynamic liver diseases, a summary and elaboration on its diagnostic potential are also carried out. Show less

Atherosclerosis is a progressive arterial disease characterized by chronic inflammation, with interleukin-27 (IL-27) implicated as both a pro- and anti-inflammatory cytokine. This prospective cohort study evaluated association of circulating IL-27 levels in peripheral artery disease patients undergoing elective endovascular revascularization, with major adverse cardiovascular events (MACE) and major adverse limb events (MALE) over a median follow-up of 311 days. Elevated IL-27 levels were significantly associated with increased risk of MACE and MALE in unadjusted analyses. After adjusting for established cardiovascular and PAD risk factors, IL-27 remained an independent predictor of MACE (HR 2.95; Show less

In people with HIV (PWH) and suppressed viral replication by antiretroviral therapy persistent T cell activation and inflammation are important contributors of the increased risk of morbidity and mortality. CD8 T cells express checkpoint receptors and are dysfunctional. IL-27, a member of the IL-6/IL-12 family has shown anti-viral properties against various human viruses, including HIV. The role of IL-27 on HIV-specific T cells remains unclear. We hypothesized that IL-27 will enhance the function of HIV-specific T cells. IL-27 effects on T cell function was evaluated by measuring cytokine secretion, proliferation, and cytotoxicity. Our findings show that IL-27 upregulates cytokine secretion and cytotoxic potential, and trafficking of proliferating HIV-specific CD8 T cells expressing checkpoint receptors TIGIT and PD-1. Unbiased clustering analysis showed that IL-27 may have differential effects on distinct populations of HIV-specific T cells. Altogether these results suggest that IL-27 may enhance T cell function in the setting of chronic HIV infection. Show less

The integration of serum biomarkers and gene polymorphisms may enhance early prognostic assessment in sepsis. Early and accurate prediction of outcomes is crucial for optimizing treatment strategies and improving survival. However, the clinical utility of combining genetic markers with conventional inflammatory indicators remains insufficiently validated. In this retrospective cohort ( 6 predictors were retained - PCT, CRP, lactate (LAC), lactate clearance rate (LCR), TLR4 rs4986790, and PPARγ rs1801282. The nomogram achieved AUC 0.885 (95% CI 0.812-0.943) with sensitivity 88.6% and specificity 73.9%; calibration was good (H - L χ This integrative biomarker-genotype model demonstrated strong internal performance and potential clinical utility for individualized risk stratification in sepsis. The results support combining genetic susceptibility and inflammatory biomarkers for enhanced prognostic precision, although external and multi-ethnic validation remains warranted before widespread adoption. Show less

Thyroid-associated ophthalmopathy (TAO) is characterized by inflammation and tissue remodeling, including fibrosis and adipogenesis. Here, we identify interleukin-27 (IL-27) as a negative feedback immunomodulator in TAO. Serum IL-27α levels were significantly elevated in patients with TAO compared with healthy and inflammatory disease controls. In orbital fibroblasts (OFs), exogenous IL-27 suppressed IL-1β-induced proinflammatory cytokines and reduced hypoxia-induced NLRP3 inflammasome activation. IL-27 also attenuated TGF-β-driven fibrosis via p38 MAPK signaling in CD90 Show less

Regulatory B cells (Bregs) contribute to immune homeostasis via IL-10-dependent and independent pathways. To dissect additional mediators, we investigated splenic derived GM-CSF/IL-15 fusokine (GIFT15)-induced Bregs in experimental autoimmune encephalomyelitis (EAE) using transcriptomics and functional validation. Bulk RNA-seq of splenic Bregs revealed upregulation of Ccl3, GzmB, and Il27 subunits compared to resting B cells. Functional studies showed that CCL3-deficient Bregs failed to suppress disease, whereas GzmB-deficient Bregs retained efficacy, and IL-27 receptor signaling in recipients was dispensable. Flow cytometry demonstrated that CCL3 expression correlated with FoxP3⁺ Treg and Tr1 expansion, along with CD206⁺ macrophage polarization. In the CNS, transient, tissue-dependent increases in oligodendroglial markers O4 and GalC were detected. Collectively, these findings identify CCL3 as a non-redundant effector of Breg-mediated protection, acting primarily through peripheral T-cell and myeloid remodeling, with secondary CNS impacts. These results highlight the translational potential of CCL3-competent, spleen-derived GIFT15 Bregs for therapeutic modulation of autoimmune demyelination. Show less

Sepsis, a life-threatening organ dysfunction caused by dysregulated host responses to infection, has emerged as a leading cause of mortality in ICU patients. Macrophages, crucial effector cells in innate immunity, play pivotal regulatory roles in sepsis pathogenesis. While Programmed death-ligand 1 (PD-L1), a key immune checkpoint molecule, is traditionally believed to exert immunosuppressive effects through membrane anchoring, its involvement in macrophage polarization during sepsis remains unclear. This study investigated the spatial distribution of PD-L1 in macrophages and its regulatory effects on inflammatory responses during sepsis. This study investigated PD-L1’s regulatory role in macrophage polarization through RNA sequencing, Immunoprecipitation-mass spectrometry, molecular docking, and site-directed mutagenesis, with preliminary validation in C57BL/6 mice. Using GEO database analysis combined with qRT-PCR and Western blotting, we confirmed elevated PD-L1 expression in sepsis and M1-polarized macrophages. Laser scanning confocal microscopy demonstrated dual localization of PD-L1, appearing both on the plasma membrane and intracellularly within M1 macrophages. RNA sequencing revealed PD-L1’s promotion of M1 polarization through enhanced AIM2 expression in the NOD-like receptor pathway. Integrated analyses employing mass spectrometry, molecular docking, site-directed mutagenesis, and Western blotting demonstrated PD-L1 binding to AIM2, which augmented expression of downstream effector molecules (IL-18 and IFN-γ) and potentiated STAT1 activation. Silencing AIM2 by siRNA or IL-18 antagonism reversed PD-L1-induced M1 markers (IL-27, IL-6, iNOS/NO). PD-L1 was further shown to exacerbate pathological progression in septic mouse models. Our study demonstrated that sepsis-induced PD-L1 overexpression in macrophages exacerbates pathological progression by upregulating AIM2 expression, binding to AIM2 to enhance IL-18 production, which activates STAT1 to drive M1 polarization. The online version contains supplementary material available at 10.1186/s12964-025-02578-1. Show less

Neonatal necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease of premature infants, characterized by immune dysregulation and compromised intestinal barrier integrity. Interleukin-27 receptor α (IL-27Ra), a critical component of the JAK-STAT signaling pathway, exhibits dual pro- and anti-inflammatory roles in various inflammatory conditions. However, its role in NEC pathogenesis remains unclear. To elucidate the functional role of IL-27Ra in NEC development and assess its potential as a therapeutic target. A multi-tiered approach was employed, including integrative analysis of clinical NEC specimens by single-cell and bulk RNA sequencing, and a neonatal mouse NEC model. NEC was induced in mice via hyperosmolar formula feeding combined with LPS gavage, intermittent hypoxia, and cold stress. Additional experiments included immunofluorescence staining for IL-27Ra, cytokine profiling (ELISA, quantitative real-time PCR (qPCR)), use of IL-27Ra knockout (IL-27Ra Show less

This study aims to investigate how Bifidobacterium breve BBr60 improves obesity-related metabolic disorders by modulating the gut microbiota-SCFAs axis, thereby affecting inflammatory factors and metabolic hormones. A randomized, double-blind, placebo-controlled trial was conducted. A total of 75 individuals with obesity subjects (BMI ≥ 28) were enrolled and randomly assigned to either the BBr60 intervention group (10 billion CFU daily) and the placebo group. After the 12-week intervention, 65 participants (BBr60: n = 33; placebo: n = 32) completed the study and were included in the primary analysis. All participants received standardized nutritional counseling aimed at a moderate energy intake (~ 1800 kcal/day, including a daily intake of 25 g of dietary fiber.). Every week, we call participants at a fixed time to inquire about their weekly diet and weight changes, and provide dietary suggestions for the following week based on the inquiry results. Participants were instructed to maintain their usual physical activity levels throughout the study. The composition of the gut microbiota was analyzed by 16 S sequencing, fecal SCFAs were detected by GC-MS, and serum levels of IL-27, IL-1β, and metabolic hormones were measured using ELISA technology. Metabolic indicators such as body weight, body fat percentage, and HOMA-IR were also assessed. The BBr60 intervention significantly increased fecal butyrate levels (p < 0.001), accompanied by a decrease in IL-1β levels (p < 0.05) and an upregulation of IL-27 (p < 0.01). In terms of metabolic hormones, leptin (LEP), adiponectin (ADPN), connecting peptide (C-P), pancreatic polypeptide (PP), peptide YY (PYY), Glucose-dependent insulinotropic polypeptide (GIP), and Glucagon-Like Peptide-1 (GLP-1) were all significantly elevated (p < 0.05), while Homeostasis Model Assessment for Insulin Resistance(HOMA-IR) was significantly reduced in the BBr60 group (p < 0.05). In the control group, C-P, PP, and GIP were significantly increased (p < 0.05), whereas LEP, ADPN, PYY, GLP-1, and HOMA-IR showed no difference before and after the 12-week period. Correlation analysis indicated that butyrate levels were significantly positively correlated with GLP-1 and IL-27, and negatively correlated with IL-1β. Bifidobacterium breve BBr60, by remodeling the gut microbiota-SCFAs axis, inhibits the pro-inflammatory factor IL-1β, activates the anti-inflammatory signal IL-27, and synergistically regulates the metabolic hormone network (such as GLP-1, ADPN), significantly improving obesity-related metabolic disorders. This study provides a theoretical basis and intervention targets for the clinical application of probiotics targeting the "microbiota-SCFAs-inflammation/hormone axis," and future research can explore precise probiotic treatment regimens based on individual microbiota characteristics. Show less

Suicide is a leading global cause of mortality, with major depressive disorder (MDD) contributing significantly. Neuroimmune mechanisms, particularly inflammation, are increasingly recognized in the pathophysiology of depression and suicidal ideation. This study investigated the relationship between inflammatory cytokines and suicidal ideation in patients with MDD. A two sample Mendelian randomization analysis using Genome-Wide Association Study data was performed to evaluate the associations between 16 inflammatory cytokines and suicidal ideation. Then the patients with MDD, stratified by suicidal ideation severity were assessed for peripheral cytokine levels (interleukin [IL])-2, IL-4, IL-6, IL-10, interferon-gamma [IFN-γ], IL-17, IL-12, IL-27, and tumor necrosis factor-α) using flow cytometry and enzyme-linked immunosorbent assay. MR analysis revealed significant associations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and IL-27 with negative and positive effects, respectively. Individuals with high suicide risk exhibited elevated IL-27, IL-12, IFN-γ and IL-4 compared with low suicide risk. There are genetic associations between IL-27 and suicidal ideation, which is biologically corroborated by elevated peripheral IL-27 levels in high-risk suicidal individuals, highlighting its potential as a clinically viable biomarker for assessing suicidal risk in depressive patients. Show less

Regulatory T (Treg) cells express high levels of the IL-27R, and in the setting of infection and autoimmunity, the cytokine IL-27 promotes Treg cell activities that mitigate tissue pathology. However, IL-27 appears dispensable for Treg cell development and maintenance as lineage-specific depletion of the IL-27R on Treg cells does not impact these populations at steady state. In contrast, when mice were generated in which the Treg compartment comprised a mix of IL-27R-sufficient and -deficient Treg cells, those that lacked IL-27R were at a competitive disadvantage. Aging experiments illustrate that IL-27R-deficient Treg cells are preferentially eroded, and this defect was associated with reduced expression of CD122, the β chain of the IL-2/15R. Moreover, blockade of CD122 led to a similar loss of Treg cells, and in vitro and in vivo studies highlight that IL-27 promotes Treg cell expression of CD122 and improves responsiveness to IL-2/15. These datasets reveal that homeostatic IL-27 signals provide a competitive advantage that shapes the composition of the Treg cell pool by modulating responsiveness to growth factors. Show less

The tumor microenvironment (TME) is a highly dynamic network shaped by immune, vascular, and stromal interactions, further modulated by extracellular factors. The high tumor heterogeneity complicates treatment due to evolving resistance. Biodynamic imaging (BDI), a 3D coherence-gated holography technique, quantifies intracellular motion to assess phenotypic responses to therapy. We applied BDI to prostate cancer (PCa) treated with IL-27-based combinations to evaluate the dynamic responses of immunotherapy. This study is the first to integrate BDI with RNA-seq to correlate physiological changes with gene expression. Using a subcutaneous PCa model, tumors were treated ex vivo with chemotherapy and immunomodulatory agents. BDI enabled capturing motion frequency shifts (0.01-12.5 Hz), while RNA-seq revealed the molecular changes in the tumors. IL-27 showed potential to modulate the immunologically "cold" TME and enhance therapeutic efficacy. This integrative approach offers a novel platform for evaluating combination strategies in PCa and may inform more effective treatment decisions. Show less

Adverse pregnancy outcomes represent a global health burden. Bacterial infection and subsequent inflammation in gestational membranes lead to immunological and physiological changes that contribute to adverse pregnancy outcomes. Although animal models of infection during pregnancy are useful to interrogate tissue and cellular level changes in host responses, these models also have numerous drawbacks, including cost, complexity, and ethical considerations. The advent of organ-on-a-chip models provides cutting-edge new approaches to model host-pathogen interactions in multicellular organ and tissue environments. In this work, we employ an organ-on-a-chip model of the maternal-fetal interface as a tool to study immunological responses to infection with the perinatal pathogen, Group B Show less

Coronavirus disease 2019 (COVID-19) has been widely associated with intense systemic inflammation, endothelial injury, and a high incidence of thrombotic complications, which together contribute to disease severity and poor clinical outcomes. While endothelial dysfunction, dysregulated cytokine production, and oxidative stress are recognized features of severe COVID-19, the direct impact of circulating factors from infected individuals on endothelial cell behavior remains insufficiently characterized. Here, we examined how serum from patients with severe COVID-19 and from convalescent individuals modulates endothelial activation, inflammatory responses, and oxidative stress using human umbilical vein endothelial cells as an in vitro model. Venous blood samples were collected from individuals with severe COVID-19 (n = 13), convalescent patients (n = 11), and healthy volunteers (n = 7) during the initial phase of the COVID-19 pandemic. Human umbilical vein endothelial cells (HUVEC) were maintained in culture and exposed to 15% serum from each study group after a period of serum deprivation. The expression of genes associated with endothelial activation, thrombosis, inflammation, and oxidative stress was analyzed by quantitative real-time PCR at defined time points. In addition, the endothelial secretory profile was evaluated in cell culture supernatants using multiplex bead-based immunoassays. Statistical analyses were performed using one-way ANOVA followed by appropriate post hoc tests, receiver operating characteristic (ROC) curve analysis to assess the discriminatory capacity of biomarkers, and multivariate linear regression to identify factors associated with disease severity. We investigated the role of the endothelium in modulating the cytokine storm in severe COVID-19. HUVEC were stimulated with serum from patients with severe COVID-19, convalescent individuals, and healthy volunteers. Stimulation with serum from severe cases induces significant increases in These findings suggest that HUVEC serves as a promising biological sensor for detecting inflammatory responses in COVID-19 patients and shows the crucial role of the endothelium in sustaining the cytokine storm that contributes to patient severity and mortality. Show less

Bone remodelling is a physiological process influenced by mechanical stimuli such as those generated during orthodontic treatment. Biochemical markers allow the phases of remodelling to be identified, its progression to be assessed, alterations to be detected and scaffold-based tissue regeneration to be evaluated. This study reviews the main markers involved in bone formation and resorption, highlighting their clinical relevance. A literature search was conducted in biomedical databases, selecting studies that analysed crevicular gingival fluid samples in areas of tension and compression. The markers were classified according to their function and location, and their baseline values, temporal variations and methods of analysis were compiled. Among the markers of bone formation, Osteoprotegerin (OPG), Transforming Growth factor β1 (TGF-β1) and Interleukin 27 (IL-27) stand out; while resorption markers include Receptor Activator of Nuclear Factor appa β Ligand (RANKL), Tumour Necrosis Factor (TNF-α) and Interleukin 1β (IL-1β). The results show different expression patterns depending on the type of force applied and the timing of the follow-up, allowing molecular profiles associated with each phase of remodelling to be established. This characterisation improves our understanding of tooth movement and provides a basis for the development of more precise scaffolds and functional biomaterials in orthodontics. Show less

Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic β-cells. Current therapies fail to address the multiple mechanisms driving disease progression. We developed an oral Female non-obese diabetic (NOD) mice were treated with the oral vaccine, GAST-17, or their combination. Blood glucose levels, islet histology, immune cell infiltration, cytokine profiles, and regulatory T cell populations were assessed. Functional assays included antigen-specific stimulation, adoptive transfer, and analysis of immunoregulatory gene expression. Combination therapy demonstrated superior efficacy in both diabetes reversal and prevention. In reversal studies, diabetes remission was achieved in 80% of mice receiving the combination therapy, compared with 63% in the vaccine-only group and 5% in the GAST-17-only group. In prevention studies, diabetes onset was prevented in 80% of mice receiving the combination therapy, compared with 70% in the vaccine-only group and 30% in the GAST-17-only group. Therapeutic effects were associated with increased antigen-specific regulatory T-cells, reduced islet-infiltrating lymphocytes, preserved insulin-positive islet area and β-cell mass, and modulation of cytokine profiles, including elevated IL-10 and TGF-β and reduced IFN-γ, GM-CSF, IL-1α, and IL-12. Upregulation of immune checkpoint molecules (CTLA-4 and PD-L1) and immunoregulatory mediators (AhR, IDO, and IL-27) was observed, suggesting a potential contribution to immune homeostasis. The combination of the oral Show less

Mutations in LRRK2, a leading genetic cause of Parkinson's disease (PD), are linked to immune dysregulation, but the immune profiles in the periphery and central nervous system (CNS) remain incompletely defined. This study utilized a large cohort of serum samples (n = 651) and matched CSF samples (n = 129) from LRRK2 mutation carriers and non-carriers, with and without PD, to assess immune regulators using Luminex immunoassay. After correction for multiple comparisons, LRRK2 mutations were associated with significantly elevated serum levels of SDF-1 alpha and TNF-RII, while CSF markers such as BAFF, CD40L, and IL-27 were nominally reduced. Regardless of LRRK2 status, PD was associated with nominally lower levels of inflammatory analytes in CSF, with minimal changes observed in serum. Correlation analyses revealed distinct immune profiles between serum and CSF, suggesting compartmentalized immune responses. These findings highlight immune alterations in LRRK2 mutation carriers and PD, providing potential serum markers for monitoring immune responses and avenues for mechanistic studies. Show less