Front Immunol. 2026 Sep 2;17:1902053. doi: 10.3389/fimmu.2026.1902053. eCollection 2026.

ABSTRACT

Childhood asthma is a highly heterogeneous chronic respiratory disease, and its onset and progression are intricately linked to genetic susceptibility, environmental exposure, immune development, and the establishment of the early-life microbiome. In recent years, studies on the gut and respiratory microbiomes have suggested that the composition, metabolic functions, and interactions of microbial communities with the host immune system may be involved in the formation of asthma susceptibility, shaping of inflammatory phenotypes, and disease progression in children. The gut-lung axis, as an important pathway connecting gut microbiome, respiratory immunity, and systemic inflammatory responses, provides a new perspective for understanding the early mechanisms of childhood asthma. This article reviews the characteristics of the respiratory and gut microbiomes associated with childhood asthma, with a focus on the roles of the gut-lung axis, microbial metabolites, mucosal immune regulation, and environmental exposure. It also evaluates the research progress of probiotics, prebiotics, nutritional interventions, and novel microecological therapies. Additionally, the potential of microbial maturity, microbial metabolites, and immunophenotypes as biomarkers for risk prediction, phenotype stratification, and treatment response is analyzed. Furthermore, the role of multi-omics integration in supporting the identification of responsive populations, matching of intervention strategies, and dynamic monitoring of efficacy is discussed. Current evidence suggests that the microbiome offers promising targets for risk assessment and precision prevention of childhood asthma. However, relevant research still faces challenges such as ambiguous causality, high cohort heterogeneity, limited reproducibility of candidate biomarkers, inconsistent intervention outcomes, and insufficient evidence of long-term safety. At present, most biomarkers and multi-omics models remain in the stage of association discovery, lacking unified thresholds, cross-cohort validation, and biomarker-guided randomized controlled trials in children. Therefore, they cannot be routinely used for patient stratification or intervention selection. Future efforts should rely on standardized longitudinal birth cohorts, multi-omics integration, external validation, and high-quality clinical trials to clarify the incremental value of microbiome biomarkers over traditional clinical indicators and their clinical utility in the individualized management of childhood asthma.

PMID:42751182 | PMC:PMC13580037 | DOI:10.3389/fimmu.2026.1902053

Diagnostics (Basel). 2026 Aug 22;16(17):2686. doi: 10.3390/diagnostics16172686.

ABSTRACT

Microvascular invasion (MVI) is a critical prognostic indicator for recurrence and survival in hepatocellular carcinoma (HCC); however, its accurate preoperative assessment remains clinically challenging. Postoperative histopathology is subject to sampling bias and time delays, while traditional imaging techniques lack the molecular specificity required to predict MVI. Liquid biopsy, through the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), circulating tumor RNA (ctRNA), and extracellular vesicles (EVs), provides a minimally invasive approach for capturing tumor-derived molecular and cellular signals associated with vascular invasion. This narrative review comprehensively summarizes the current evidence linking these four liquid biopsy analyte categories to MVI in HCC, evaluates their integration into multi-omics predictive models, including multi-marker, clinicopathological-integrated, and imaging-integrated strategies, and proposes an evidence-level framework that categorizes blood biomarkers according to the strength of their support for MVI prediction, distinguishing direct histopathological validation from indirect associations with aggressive tumor biology. Key challenges are critically examined, including the variable specificity of individual biomarkers for MVI, the lack of head-to-head comparative studies, the absence of standardized pre-analytical and analytical protocols, and the methodological limitations of current prediction models. As a narrative review, this work does not employ systematic review methodology, and the evidence synthesis should be interpreted accordingly. The review provides a framework for understanding how liquid biopsy-based MVI risk stratification may inform surgical and perioperative decision-making following prospective validation.

PMID:42739118 | PMC:PMC13564874 | DOI:10.3390/diagnostics16172686

Biology (Basel). 2026 Sep 4;15(17):1549. doi: 10.3390/biology15171549.

ABSTRACT

OBJECTIVE: This study established a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) to evaluate pathological damage, collagen deposition, inflammatory cytokine levels, and key gene/protein expression following Hedyotis diffusa water extract (HDWE) intervention. Combined with ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), transcriptomic analysis, and molecular simulation, this study identified the bioactive components of HDWE, evaluated their potential interactions with ALI-related targets, and explored the multi-omics-based protective mechanisms of HDWE.

METHODS: Thirty-six Sprague-Dawley (SD) rats were randomly divided into six groups: Control group, ALI group, DXMS group, HDWE-L group (100 mg/kg), HDWE-M group (200 mg/kg), and HDWE-H group (300 mg/kg). Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to evaluate lung pathological changes and collagen deposition. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum tumor necrosis factor-α TNF-α interleukin-1β IL-1β, erleukin-6 (IL-6), and interleukin-10 (IL-10) levels. Transcriptomic analysis identified differentially expressed genes (DEGs), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), receiver operating characteristic (ROC), and immune infiltration analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) detected the mRNA expression levels of SPHK1, RELA, and NFKBIA. Immunohistochemistry evaluated the expression of eight hub targets, including endothelin-1 (EDN1), sphingosine kinase 1 (SPHK1), intercellular adhesion molecule 1 (ICAM1), interleukin-17 (IL-17), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), NF-κB p65 (encoded by RELA), WT1-associated protein (WTAP), and myeloperoxidase (MPO). UHPLC-Q-Orbitrap HRMS characterized HDWE constituents. Molecular docking analysis was performed between 22 compounds and eight hub targets, followed by 100 ns molecular dynamics simulations and molecular mechanics-Poisson-Boltzmann surface area (MM/PBSA) binding free energy calculations for five core targets. Compared with the control group, the ALI group showed increased levels of TNF-α (86%), IL-1β (107%), and IL-6 (66%), accompanied by a 43% reduction in IL-10 and a 300% increase in lung collagen deposition. All HDWE doses alleviated inflammatory responses, with medium-dose HDWE showing the most pronounced effects. Specifically, medium-dose HDWE increased IL-10 levels by 52% and reduced IL-6, TNF-α, and IL-1β levels by 18%, 22%, and 11%, respectively. Transcriptomic analysis identified 2512 DEGs between the control group and ALI groups, 832 exclusive DEGs between the ALI group and HDWE-M groups, and 876 overlapping DEGs enriched in TNF, IL-17, and NF-κB signaling pathways. The eight-hub-gene diagnostic model achieved an area under the curve (AUC) of 0.969. RELA, SPHK1, and four other hub genes showed positive correlations with Th1, Th17, and neutrophil infiltration. In the ALI group, SPHK1, RELA, and NFKBIA mRNA expression levels were 1.30-, 0.96-, and 0.71-fold of those in the control group, respectively. Compared with the ALI group, high-dose HDWE treatment and low-dose HDWE treatment reduced SPHK1 expression to 0.62- and 0.57-fold, respectively, and increased NFKBIA expression to 1.68- and 1.58-fold, respectively. High-dose HDWE treatment reduced RELA expression to 0.43-fold. The expression levels of inflammation-related proteins were increased in the ALI group and were reduced after HDWE treatment. Twenty-two HDWE components were identified, 16 of which met the docking criteria. Asperulosidic acid exhibited favorable predicted binding affinities with all eight targets, with calculated binding free energies of -14.74, -14.92, -17.58, -23.04, and -16.10 kcal/mol for MPO, IL-17, NF-κB p65, PTGS2/COX-2, and SPHK1, respectively.

CONCLUSIONS: This study provides systematic in vivo pharmacodynamic and in silico component-target evidence regarding the protective effects of HDWE against LPS-induced ALI. HDWE treatment increased NFKBIA expression and reduced SPHK1, RELA, and multiple inflammatory protein levels, suggesting that HDWE may regulate the IL-17/NF-κB-associated inflammatory network, although direct causal relationships require further validation. Asperulosidic acid may represent a key bioactive component with broad target-binding potential. This study was limited by the use of an LPS-induced rat ALI model without gene knockout or target inhibitor validation; therefore, further functional experiments are required to confirm the proposed regulatory mechanisms.

PMID:42737981 | PMC:PMC13564518 | DOI:10.3390/biology15171549