Treponema pallidum (T. pallidum) can invade various organs and tissues. However, there have been few studies on the pathological injury of T. pallidum to the testis and sperm. The NOD-like receptor protein 3 (NLRP3) inflammasome, upon activation, leads to pyroptosis-a programmed, pro-inflammatory cell death process, and promotes inflammatory responses. Previous investigations have found that the NLRP3 inflammasome is elevated in the testis tissues of rabbits infected with T. pallidum. This study aimed to investigate whether T. pallidum induced pathological injury of the rabbit testis and sperm through NLRP3 inflammasome-mediated pyroptosis. While rabbits in the T. pallidum group received an intratesticular injection of 1 mL of a bacterial suspension containing 10⁷/mL treponemes, those in the sham group were administered an equal volume of normal saline to serve as the injection procedure control. 14 days later, testis tissues were harvested for IHC and H&E staining, and analysis of qPCR. In vitro, GC-2spd cells were stimulated by T. pallidum (MOI = 20). After administering MCC950, the expression levels of the inflammasome NLRP3 and downstream pyroptosis-related molecules were subsequently detected. T. pallidum caused obvious pathological damage to the rabbit testis and sperm reduction. Meanwhile, the gene expression levels of NLRP3, ASC, GSDMD, Caspase-1, IL-Iβ, and IL-18 in the T. pallidum group were higher than those of the sham group. Additionally, T. pallidum induced cell injury and pyroptosis in GC-2spd cells, which was improved by the NLRP3 inflammasome inhibitor MCC950. Our findings validated that T. pallidum induced pathological damage to the testis and sperm reduction via NLRP3 inflammasome activation and pyroptosis. By specifically inhibiting the NLRP3 inflammasome, MCC950 has the potential to ameliorate sperm cell damage under in vitro conditions via the blockade of pyroptotic cell death.

High mortality of pediatric acute respiratory distress syndrome (PARDS) demands new biomarkers. The study aims to clarify the clinical value of miR-192-5p in PARDS and its regulatory role in inflammatory responses. Baseline data and serum samples were collected from healthy children, sepsis children, and sepsis-induced PARDS subjects. The receiver operating characteristic curve (ROC), Kaplan-Meier curve and multivariate Cox regression were used to assess miR-192-5p’s diagnostic and prognostic value for PARDS. The relationship between miR-192-5p and each index was evaluated by correlation analysis. The expression of miR-192-5p, inflammatory factors and ZEB2 in the subjects’ serum and human pulmonary microvascular endothelial cells (HPMECs) were detected by RT-qPCR. The cell viability and secretion of inflammatory factors were evaluated by CCK-8 and ELISA kit. Bioinformatic prediction combined with dual-luciferase reporter assay was used to verify the target genes. miR-192-5p was significantly low-expressed in PARDS patients’ serum. MiR-192-5p was a prognostic protective factor for PARDS, and low miR-192-5p indicated poor prognosis. MiR-192-5p was negatively correlated with TNF-α, IL-6, IL-1β, and APACHE II score. LPS treatment led to reduced HPMECs viability, excessive inflammatory factor production, and down-regulated miR-192-5p expression. Overexpression of miR-192-5p mimic could partially reverse the above phenomena, while knockdown could aggravate the above phenomena. ZEB2 was a downstream target gene of miR-192-5p. miR-192-5p serves as a diagnostic biomarker for PARDS and links to poor prognosis. Downregulation of miR-192-5p may promote LPS-induced inflammatory response and induce HPMECs cell viability by targeting ZEB2, thereby involving in the progression of PARDS.

Common Variable Immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults. While infections are common, over 50% of patients exhibit autoimmune and immune activation related complications. Chronic inflammation from dysbiosis may affect the heart in CVID, though its relationship with gut barrier and echocardiographic findings is still unclear. This study investigates the associations between intestinal permeability, Trimethylamine N-oxide (TMAO) levels, immune activation, and cardiac function in CVID patients. The study included 31 CVID patients and 31 matched healthy controls. Serum zonulin, TMAO, soluble CD14 (sCD14), soluble CD25 (sCD25), Tumor Necrosis Factor-alpha (TNF-α), and IL-17 A levels were measured by ELISA. Cardiac function was assessed using speckle-tracking echocardiography (STE), focusing on global longitudinal strain (GLS). Increased levels of zonulin and TMAO were observed in CVID patients. sCD14 and sCD25 levels correlated strongly with TMAO. TMAO showed a negative correlation with Ejection Fraction and a positive correlation with Pulmonary Artery Pressure (PAP). No significant differences were found in serum TNF-α and IL-17 A levels in the compared groups. Compared to the control group (-19.90 ± 2.41), a remarkable reduction in mean GLS (-18.13 ± 3.13) was determined in the CVID group. These results are early indicators of myocardial dysfunction. Strain analysis showed a significant decrease in negative Apical 4-Chamber View Basal Longitudinal Strain (AP4B) and Apical 3-Chamber View Basal Longitudinal Strain AP3B values in the CVID group (p = 0.012 and p = 0.027). In this study, elevated serum zonulin and TMAO levels correlated with increased intestinal permeability and immune activation in CVID. High TMAO was linked to early myocardial dysfunction, highlighting the potential of microbiome-targeted therapies and advanced echocardiography for early cardiac risk detection in CVID.

BackgroundT lymphocyte dysfunction is closely associated with immunosuppression in sepsis, whereas the underlying mechanisms are not fully understood.ResultsIn this study, we established a mouse model of cecal ligation and puncture (CLP)-induced sepsis and observed immunometabolic alterations in splenic T cells. Serum energy metabolites related to glycolysis and the tricarboxylic acid (TCA) cycle were imbalanced. Splenic T cells from septic mice showed a shift in subset distribution, with decreased naïve T cells and increased effector populations, along with concurrent activation and exhaustion phenotypes. Notably, mitochondrial mass and mitochondrial membrane potential were significantly diminished in both CD4+ and CD8+ T cell, correlated with increased programmed cell death protein 1 (PD-1) expression. Transmission electron microscopy further confirmed mitochondrial morphological alterations in CLP-derived CD3+ T cells. Furthermore, seahorse assays demonstrated impaired metabolic reprogramming capacity in activated CLP splenic CD3+ T cells, with suppressed glycolytic and oxidative phosphorylation responses. This impairment was coupled with reduced fold-increases in mitochondrial mass and mitochondrial membrane potential levels upon activation in both CD4+ and CD8+ T cell compared to controls. Clinically, peripheral T cells from septic patients showed elevated CD69 and PD-1 expression, a significant increase in CD39 and a decrease in CD73, increased mitochondrial mass and decreased mitochondrial membrane potential, particularly in those with septic shock.ConclusionsOur findings provide several layers of T cell dysfunction in sepsis, linking subset redistribution, an exhausted phenotype, mitochondrial impairment, and reduced proliferative capacity, suggesting that future therapeutic interventions aiming to reverse sepsis-induced immunosuppression may require a combinatorial approach.

BackgroundMonocyte chemoattractant protein-1 (MCP-1) has been utilized as a prognostic indicator for sepsis patients; however, the findings have been inconsistent. This meta-analysis seeks to elucidate the prognostic significance of MCP-1 in individuals diagnosed with sepsis.MethodsWe systematically queried four databases (Web of Science, PubMed, EMBASE, Cochrane Library) to identify studies published from the establishment of the databases until January 2025. Hazard ratios (HRs) with 95% CIs were employed to evaluate the prognostic significance of MCP-1 in this patient population. In our study, the Newcastle-Ottawa Quality Assessment Scale was evaluated for quality assessment, and Funnel plot was used for publication offset.ResultsA total of 592 patients from eight studies were included in the evaluation. The findings revealed that MCP-1 levels were significantly elevated in non-survivors compared to those who survived [SMD = 0.54, 95% CI: 0.25–0.82, P = 0.0002]. Our study demonstrated that elevated levels of MCP-1 were significantly associated with an unfavorable prognosis in patients with sepsis, with a hazard ratio (HR) of 1.36 (95% confidence interval: 1.25–1.48; P < 0.00001) using a random-effects model. The funnel plot indicated no publication bias.ConclusionThis meta-analysis suggests that elevated levels of MCP-1 could serve as a valuable prognostic indicator in sepsis patients, however, this conclusion still requires validation through higher-quality studies with longer-term follow-up.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12865-025-00783-8.

ObjectiveBased on the bidirectional relationship between sleep and macrophages in healthy and diseased states, this systematic review and meta-analysis investigated the effect of disrupted sleep on macrophage polarization.MethodsA literature search was conducted in PubMed, Scopus, and Web of Science (WoS) databases up to October 2023, identifying English-language studies on disrupted sleep’s effects on macrophage polarization. After screening and data extraction, the standardized mean difference (SMD) with a 95% Confidence Interval (CI) was calculated for M1 pro-inflammatory and M2 anti-inflammatory markers. Heterogeneity was assessed using Cochran’s Q test and the I-square (I2) statistic, and subgroup analyses were performed. The methodological quality was assessed using SYRCLE’s RoB tool. Publication bias was examined through Egger’s test and the trim-and-fill method, and a sensitivity analysis was also conducted. The meta-analysis was performed using STATA version 14.2 software.ResultsThirteen studies were included. Results indicated that disrupted sleep significantly increased CD11c levels [SMD: 2.450, 95% CI: 1.517 to 3.383, I² = 11.7%], and decreased CD206 levels [SMD: -2.616, 95% CI: -4.911 to -0.321, I² = 83.3%]. The association between disrupted sleep and M1/M2 was uncertain, with sex identified as a potential source of heterogeneity. No publication bias or sensitivity was detected, which strengthens the reliability and robustness of the findings.ConclusionDisrupted sleep significantly influenced macrophage polarization towards a CD11c+ M1 inflammatory phenotype. Given the heterogeneity and limited number of studies, these findings should be interpreted as exploratory. Further research on the underlying mechanisms, particularly concerning biological sex, to better understand sleep’s impact on immune function and treatment strategies for inflammatory conditions.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12865-025-00770-z.

The mechanism of epitope mimicry could have implications for the safety of vaccine development. OmpA is one of the most promising antigens of Acinetobacter baumannii. This property convinced us to investigate OmpA’s potential to trigger autoimmune responses. To this end, BLAST searches were performed using the OmpA sequence and its overlapping peptides to find identical peptides in the human proteome. These peptides were analyzed for their epitopic and HLA binding properties. The population coverage was then calculated for the peptides. OmpA showed high identity among numerous strains of A. baumannii and had no similar counterparts in the human proteome. Three OmpA peptides (TKNYDSKI, LSLARANS, and GQEAAAPA) shared identity and similarity with human proteins. Amongst, LSLARANS, which was found in Isthmin-1, the one with the highest potential to induce autoimmune responses was identified. LSLARANS was found in a B-cell positive assay of OmpA and acted as an HLA binder (such as HLA-A*03:01). Approximately 18% of the world’s population were determined to be more susceptible to probable A. baumannii-post-infection autoimmune disease, which could be rooted in OmpA similarity. Mutation sensitivity analyses indicated that the TKNYDSKI peptide is sensitive to engineering and modification. Given these circumstances, these peptides should be avoided in vaccine design efforts to reduce the risk of autoimmune responses.Graphical