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关键词： IL-4R alpha l   Trypanosomiasis   Neuroinflammation   Anxiety   Iloprost  

摘要： This study investigated the effects of Trypanosoma brucei infection on neuroinflammation, immune response, and behaviour in both wild-type (WT) and IL-4R alpha inhibited (IL-4R alpha l) mice. To achieve this, 9-week-old WT and IL4R alpha l mice were infected with T. brucei intraperitoneally (5 x102 parasites) and the treated groups received 200 mu g/kg/day of Iloprost intraperitoneally. Results from infected animals showed that behavioural activity and inflammation were reduced in animals treated with Iloprost. Euthanasia was performed on 12 days post-infection (dpi), and prefrontal cortex (PFC), Hippocampus (HPC) and blood were collected. PCR confirmed the presence of T. brucei in the brain and blood, demonstrating its ability to cross the blood-brain barrier. CXCL10, a key chemokine implicated in neuroinflammation, was elevated in infected mice, particularly in IL-4R alpha l mice, which lack the ability to initiate protective type 2 immune responses. Treatment with Iloprost suppressed CXCL10 expression and reduced inflammation. Behavioural assessments revealed that T. brucei infection induced anxietylike behaviours and hypoactivity. Interestingly, IL-4R alpha inhibition appeared to reduce anxiety-like behaviours in infected mice, while Iloprost treatment had an anxiolytic effect. Locomotor deficits were observed in infected mice, with IL-4R alpha l mice showing more pronounced hypoactivity. However, both Iloprost and Diminazine improved locomotor activity. At the molecular level, IL-4R alpha inhibition resulted in upregulation of proinflammatory cytokines such as TNF-alpha and elevated nitric oxide levels, contributing to CNS inflammation. Iloprost treatment reduced these markers and supported anti-inflammatory pathways. These findings highlight the complex interplay between immune regulation, neuroinflammation, and behaviour in trypanosome infection, with IL-4R alpha signalling playing a critical role in modulating disease outcomes. Therapeutic interventions targ

关键词： Sepsis   Acute respiratory distress syndrome (ARDS)   IL-27   Nrf2/HO1   Ferroptosis  

摘要： ObjectivesAcute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulated by macrophages. This study aimed to elucidate the effect of Recombinant Mouse IL-27 Protein on macrophage ferroptosis and polarization, as well as its impact on sepsis-induced *** cecal ligation and puncture (CLP)-induced sepsis model was established using wild-type (WT) or IL27R-/- mice. Then, the mice were randomly divided into 4 groups: a control group, a CLP group, an IL-27 + CLP combination group, and an IL-27, CLP, and Oltipraz combination group. RAW 264.7 cells and BMDMs were used to further determine the role and mechanism of IL-27 in *** vitro, IL-27 alone did not alter the expression of proteins linked to the ferroptosis pathway or macrophage polarization. Contrastingly, the combination of IL-27 with LPS further amplified LPS-induced alterations in the ferroptosis pathway, thereby promoting macrophage M1 polarization and inhibiting M2 polarization. Additionally, IL-27 + LPS increased ROS levels in macrophages. A sepsis-induced ARDS mouse model was then established via CLP. In vivo, IL-27 exacerbated CLP-induced lung injury in WT mice. Additionally, it decreased the expression levels of ferroptosis-related proteins (Nrf2, HO-1, GPX4) and increased those of Ptgs2 in the lung tissue of septic mice. Besides, GSH and SOD levels in lung tissue were also reduced. Moreover, IL-27 also promoted M1 polarization and inhibited M2 polarization in macrophages. In IL27R-/- mice, the effects of IL-27 were abrogated. Oltipraz inhibited IL-27-induced changes by up-regulating Nrf2 expression. Overall, this present study demonstrated that the combination of IL-27 and LPS-induced macrophage ferroptosis, promoted macrophage M1 polarization, and inhibited M2 polarization by inhibiting the Nrf2/HO-1 *** may alleviate ARDS-relat

关键词： miR-7565   Large yellow croaker ( Larimichthys crocea )   IL-13R alpha 1   Th2 immune response  

摘要： IL-4 and IL-13 are cytokines with structural homology, exerting critical functions in the Th2 immune response via binding to their respective receptor complexes and activating the MAPK and mTOR pathways. MicroRNAs (miRNAs) modulate diverse molecular processes via suppressing messenger RNA translation or inducing messenger RNA degradation. Although miR-7565 has been previously linked to embryonic development, its regulatory effects on the Th2 immune response remain unknown. In this study, miR-7565 was first identified in large yellow croaker (Larimichthys crocea), which exhibits high conservation across vertebrates. The expression of Lcil-13r alpha 1 is negatively regulated by miR-7565 through its direct binding to the 3 ' UTR of Lcil-13r alpha 1. MiR-7565 overexpression led to a notable decrease in endogenous Lcil-13r alpha 1 mRNA levels. MiR-7565 overexpression notably suppressed the activation of MEK1/2 and 4E-BP mediated by LcIL-4/13A and LcIL-4/13B. Moreover, miR-7565 weakened the stimulating impacts of LcIL-4/13A and LcIL-4/13B on T cell proliferation/differentiation, and B cell proliferation. These findings indicate that miR-7565 suppresses the signal transduction induced by IL-4/13A and IL-4/13B by targeting Lcil-13r alpha 1, thereby negatively regulating the Th2 immune response. This study advances our knowledge of miRNA-mediated regulatory mechanisms of adaptive immunity in fish.

摘要： Background: Colorectal cancer (CRC) is increasingly common in younger individuals and strongly linked to chronic inflammation. Gut microbiota and pathways like NF-kappa B/STAT3 play key roles, which highlights the therapeutic potential of natural compounds that target intestinal immunity and microbial balance. Objective: To investigate the therapeutic effects of pectic polysaccharides (PPs) from Rauvolfia verticillata in inflammation-associated CRC via the modulation of of gut microbiota and NF-kappa B/IL-6/STAT3 signaling pathways. Methods: C57BL/6 mice were subjected to azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC and treated with PP (100 mg/kg/day), the STAT3 inhibitor W2014-S (10 mg/kg), or fecal microbiota transplantation (FMT) from PP-treated donors. Histopathology, immunohistochemistry (IHC), Western blot, immunofluorescence (IF), 16S rRNA sequencing, and SCFA analysis were performed to assess inflammation, signaling pathways, gut microbiota composition, and metabolic changes. Results: PP intervention significantly mitigated AOM/DSS-induced weight loss, intestinal lesions, and disease activity index (DAI) scores while suppressing NF-kappa B and STAT3 activation. PP restored gut microbiota diversity, reduced pro-inflammatory genera, and regulated SCFA levels, particularly hexanoic those of and isohexanoic acids. FMT from PP-treated donors similarly attenuated colitis and inhibited NF-kappa B/STAT3 pathways. Conclusions: PP alleviates CRC and is associated with modulation of gut microbiota, SCFA metabolism, and NF-kappa B/IL-6/STAT3 signaling, offering a potential therapeutic strategy for inflammation-driven CRC.

关键词： Artesunate   Ovarian cancer   Ferroptosis   GP130Lys250   Pathway  

摘要： Background: Ovarian cancer (OC) is highly malignant with suboptimal current therapeutic outcomes. Ferroptosis is a novel cell death mode. Artesunate (ART) has demonstrated relatively broad-spectrum anticancer effects recently, yet whether it can suppress OC by inducing ferroptosis, along with the underlying mechanisms, warrants further exploration. Purpose: To clarify the anti-OC effect and mechanism of ART, focusing on ferroptosis induction and identify its therapeutic target. Methods: ART's anti-OC effects were assessed in vitro via cell counting kit-8, live-cell staining, scratch, and transwell assays. In vivo efficacy and safety of ART were evaluated in OC-bearing mice. Ferroptosis markers were analyzed by enzyme linked immunosorbent assay, western blot, and reverse transcription quantitative polymerase chain reaction, especially OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1)-mediated solute carrier family 7 member 11 (SLC7A11) deubiquitination was measured by coimmunoprecipitation. RNA-seq profiled transcriptional changes, and signal transducer and activator of transcription 3 (STAT3) regulation of OTUB1 was confirmed by dual-luciferase reporter and chromatin immunoprecipitation quantitative polymerase chain reaction assays. ART binding to the interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R)/glycoprotein 130 (GP130) complex was determined by bioluminescence resonance energy transfer, cellular thermal shift assay, molecular docking, and dynamics simulations. GP130 point mutations validated the functional binding site. Results: ART induced ferroptosis in OC cells by targeting GP130, inhibiting cell viability and hindering cell invasion/metastasis. In vivo, ART significantly suppressed the tumor growth of OC-bearing mice, and the tumor volume inhibitory rate and weight inhibitory rate of ART (5 mg/kg) was (82.34+4.97 %) and (78.27+4.74 %), respectively, and no side effects were observed. Mechanistically, ART bond to lysine 250 (Lys250) of GP

关键词： Chick   Gut microbiota   Phloretin   Salmonella pullorum  

摘要：

关键词： Schizophrenia   Autoimmune   Psychosis   Biomarkers  

摘要： Dear Editor, we were delighted to read the recent article in your journal about a clinical study investigating a possible link between plasma interleukin thirty-three (IL-33) levels and aggression in schizophrenia ( Zhang et al., 2025). It was fou...

关键词： Lithium-on battery   Safety   Ionic liquid   Functional separator   Flame retardant  

摘要： The development of high-performance separator materials has become crucial with the ever-increasing demands for enhanced safety and energy density of lithium-ion batteries in electric vehicles and large-scale energy storage systems. Here, a novel high-safety functionalized separator was prepared by synthesizing a composite material that encapsulates phosphorus-nitrogen-containing ionic liquid (P/N-IL) within NH2-UIO-66-Zr metal-organic framework (MOF), and then combining this composite with a polyvinylidene fluoride (PVDF) P/N-IL@NH2UIO-66/PVDF separator. This functionalized P/N-IL@NH2-UIO-66/PVDF separator significantly improves the flame-retardant performance of NCM811 batteries, effectively mitigating the risks of electrolyte combustion and explosion. Meanwhile, the porous structure of P/N-IL@NH2-UIO-66 material optimizes the Li+ transport pathways, resulting in an increase in the ionic conductivity of NCM811 battery o 3.1 x 10-4 S/cm (compared to only 3.4 x 10-6 S/cm for the pure PVDF separator). The Li+ transference number is also elevated to 0.68. Moreover, after 600 cycles at a 1C current density, the capacity retention rate reaches as high as 71 %, with an average coulombic efficiency of 96 %, substantially enhancing the electrochemical performance and cycling stability of the battery. This work offers a novel technological pathway for the development of high-safety, high-performance lithium-ion batteries, as well as for the application of ionic liquids and MOFs.

关键词： Weighted gene co-expression network analysis   WGCNA   Bisphenol A (BPA)   Preeclampsia (PE)   Single-cell RNA sequencing (scRNA-seq)   Inflammatory Signaling   Molecular Dynamics Simulation (MDS)  

摘要： In hypertensive disorders of pregnancy, particularly preeclampsia, epidemiological associations have increasingly implicated the endocrine disruptor Bisphenol A (BPA), but robust mechanistic evidence remains elusive. Building upon accumulating clinical concern and in vivo data, we pursued an integrative, multi-omic investigation to dissect whether BPA causally and directly contributes to placental maladaptation and vascular dysfunction. Two-sample Mendelian randomization analyses using large European-ancestry genome-wide association datasets demonstrated a significant, directionally concordant relationship between genetically instrumented BPA exposure and preeclampsia risk, supporting causation rather than simple correlation. Single-cell transcriptomic analysis of the maternal-fetal interface identified stromal fibroblasts as a dominant source and target of interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling. Molecular docking and Molecular Dynamics Simulations revealed that BPA binds stably within hydrophobic pockets of IL-6 and, to a lesser extent, STAT3, thereby providing a plausible physical mechanism for ligand-mediated pathway activation. Complementary experiments in human HTR-8/SVneo trophoblasts showed that nanomolar BPA exposure induced dose- and time-dependent STAT3 phosphorylation, promoted IL-6-STAT3 complex formation, and upregulated prototypical downstream genes, including SOCS3, MMP9 and IL-8, hallmarks of inflammation and extracellular matrix remodeling. The concordance between genetic, cellular, structural and functional datasets delineate an integrated cascade in which BPA perturbs fibroblast-centered IL-6/STAT3 signalling, precipitating pro-inflammatory and remodeling responses consistent with preeclampsia pathophysiology. These findings elevate BPA from an associative to a mechanistically credible, modifiable risk factor and nominate stromal IL-6/STAT3 signaling as a therapeutic target for preventing environmen

关键词： Aging   IL-1 beta   Histamine   H1 receptor   Catalepsy   Dopamine metabolism   Dorsal striatum  

摘要： Aging, the strongest risk factor for Parkinson's disease (PD), is associated with brain neuroinflammation. In parkinsonian brain, this inflammation manifests in elevated levels of interleukin-1 beta (IL-1 beta). The pathogenic significance of this factor is unclear. The presented study was aimed to examine the effect of IL-1 beta analogue, rat recombinant IL-1 beta (rrIL-1 beta), on striatal dopamine metabolism in aged rats;in parallel, cataleptogenic action of rrIL-1 beta was determined. Given the ability of IL-1 beta to induce histamine release from histaminergic fibers, the involvement of histamine H1, H2, H3, and H4 receptors in the rrIL-1 beta effects was evaluated. The male Wistar rats of 530-570 days of age were used in all experiments. The experimental groups consisted of 6 animals. The striatal levels of dopamine (DA), 3, 4 -dihydroxyphenylacetic acid (DOPAC), and tyrosine hydroxylase (TH) were determined using HPLC and ELISA;catalepsy was assessed by bar test. Daily i.c.v. administration of rrIL-1 beta for 14 days at 3.0 ng caused significant decrease in DA, DOPAC, and TH levels in the dorsal striatum;these neurochemical changes were accompanied with the development of catalepsy. The observed rrIL-1 beta effects were reversed by H1 antagonist mepyramine whereas H2 and H3/H4 antagonists ranitidine and thioperamide were ineffective. The presented results provide novel insight into functioning of the nigrostriatal pathway in aged rats. Apparently, there exists a certain IL-1 beta-histamine mechanism exerting depletion of dopamine in the dorsal striatum and initiating catalepsy;the mechanism is mediated by H1 receptors. Our data suggest that the IL1 beta-histamine interaction might contribute to the PD development, and be potential target for the treatment of parkinsonism.