Ulcerative colitis (UC) belongs to chronic inflammatory disease with a relapsing characterization. Conventional oral drugs of UC are restricted in clinical by premature degradation in the gastrointestinal tract, modest efficacy, and adverse effects. CX5461 can treat autoimmune disease, immunological rejection, and vascular inflammation. However, low solubility, intravenous administration, and non-inflammatory targeting limited its clinical application. Herein, this work aims to develop Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 (SFELNVs@CX5461) for efficient CX5461 oral delivery for UC therapy. We identified SFELNVs as nano-diameter (80 nm) with negative zeta potential (-32mV). Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 alleviated mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1β, and IL-6) expression and promoting M2 macrophage polarization. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe UC therapy.

Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature

Challenges in pediatric inherited/metabolic liver disease: Focus on the disease spectrum, diagnosis and management of relatively common disorders

Introduction: Current research underscores the critical role of the gut-skin axis in inflammatory skin disorders such as psoriasis, with growing interest in the therapeutic application of probiotics. Despite this promise, the specific mechanisms and bioactive compounds through which probiotics exert their effects remain poorly characterized. In this study, we aimed to systematically evaluate the therapeutic potential of Lactobacillus plantarum (Lp)-derived bioactive fractions in psoriasis, with a particular focus on identifying key anti-inflammatory and immunomodulatory metabolites.Methods: The microbiome characteristics of psoriasis were analyzed through open microflora data mining and bibliometrics, and the probiotics with potential therapeutic effects were identified. Four bioactive fractions from L. plantarum were extracted and characterized. CCK-8, qPCR, and flow cytometry were used to evaluate the effects of four bioactive components on oxidative stress in keratinocytes and inflammatory responses in macrophages. Metabolomics was used to analyze the metabolic profiles of bioactive components with anti-inflammatory and antioxidant properties, and to screen and identify the main metabolite that play a role. To evaluate the efficacy and safety of bioactive components in the treatment of IMQ-induced psoriasis in mice.Results: A common feature of downregulation of Lactobacillus abundance was shown in patients with four inflammatory skin diseases including psoriasis. Four bioactive fractions, namely cytoplastic membrane vesicles (CMVs), bacterial lysate supernatant (BL-S), bacterial lysate precipitate (BL-P) and cell-free fermentation supernatant (CFS), were extracted from L. plantarum ATCC BAA-793, and CMVs were identified as having typical extracellular vesicles. In efficacy evaluation, CMVs and BL-S significantly reduced the mRNA levels of inflammatory factors in macrophages and the ROS levels of inflamed keratinocytes, among which CMVs had a more significant anti-inflammatory effect and had a unique inhibitory effect on M1 polarization of macrophages. Metabolomics revealed significant differences in metabolite profiles between CMVs and BL-S, and AEA enriched in both played anti-inflammatory, antioxidant and inhibitory roles in macrophage M1 polarization. In IMQ-induced psoriasis mouse models, CMVs demonstrated superior effects over BL-S in anti-hyperkeratosis, inhibiting inflammatory factor production, and down-regulating the proportion of M1 macrophages in skin and spleen. Both showed good biosafety in vivo.Discussion: This study demonstrates that L. plantarum-derived CMVs, enriched with AEA, ameliorate psoriasis through multi-faceted mechanisms including anti-inflammation, antioxidative stress reduction, and reprogramming of macrophage polarization. These findings not only position bacterial nanovesicles as a novel cell-free therapeutic strategy for inflammatory skin diseases but also establish a functional screening platform for precision microbiome-based interventions.

Inflammatory bowel disease (IBD) presents significant clinical challenges due to its multifaceted pathogenesis and the limited efficacy of existing therapies. This study investigates the therapeutic potential of Cu–Zn@HA bimetallic nanozymes for the treatment of colitis. Through in vivo experiments, we demonstrated that these nanozymes exhibit sustained retention in the colon, facilitating effective modulation of gut microbiota composition and diversity. Notably, Cu–Zn@HA nanozymes significantly enhanced α-diversity and induced distinct alterations in microbial community structure across treatment groups. While no marked differences were observed in the Firmicutes/Bacteroidetes ratio, our biomarker analyses indicated critical shifts in bacterial populations associated with gut health and inflammatory responses. Additionally, Cu–Zn@HA nanozymes effectively scavenged reactive oxygen species (ROS) and promoted macrophage polarization, contributing to an anti-inflammatory microenvironment. Importantly, our studies confirmed the excellent safety profile of these nanozymes. Collectively, these findings underscore the promising role of Cu–Zn@HA bimetallic nanozymes as a novel therapeutic strategy for IBD, paving the way for future investigations into their clinical efficacy and safety.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most prevalent chronic liver condition in adolescents. The triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has shown promise in adult MAFLD detection but requires pediatric-specific validation, particularly when combined with anthropometric measures. This study investigated the association between modified TyG indices and MAFLD, and evaluated their predictive value in adolescents. Methods: This cross-sectional study analyzed data from 532 adolescents (12–18 years) in the 2017–2020 National Health and Nutrition Examination Survey (NHANES) with complete records. MAFLD diagnosis was based on transient elastography plus metabolic criteria. The investigators employed multivariate linear regression and restricted cubic splines (RCS) to examine linear and nonlinear relationships between modified TyG indices and CAP values. Subgroup analyses were stratified by obesity status, and sensitivity analyses were performed on the NAFLD cohort (n = 527). Receiver operating characteristic (ROC) curve analysis, using Youden's index, evaluated the predictive performance of TyG indices for MAFLD identification. Results: Among 130 MAFLD adolescents (vs 402 controls), modified TyG indices demonstrated significantly stronger associations with CAP in fully adjusted models compared to the original TyG index. TyG-WC showed the highest diagnostic accuracy (AUC = 0.923, 95%CI:0.900–0.947), followed by TyG-BMI (AUC = 0.917) and TyG-WHtR (AUC = 0.915), while the original TyG index performed poorly (AUC = 0.673). Subgroup analyses revealed particularly strong associations in non-obese participants, and sensitivity analyses confirmed result robustness after excluding potential confounders. Optimal cutoff values provided clinically useful screening thresholds, with TyG-WC achieving 94% sensitivity at 665.94. Conclusion: This study demonstrates that modified TyG indices incorporating anthropometric parameters (particularly TyG-WC) significantly outperform the original TyG index for MAFLD detection in adolescents, with superior diagnostic accuracy (AUC 0.915–0.923). The robust predictive performance maintained in sensitivity analyses and non-obese subgroups supports their clinical utility as simple, non-invasive screening tools for pediatric MAFLD risk stratification.