J Vis Exp. 2026 Sep 8;(235). doi: 10.3791/71404.

ABSTRACT

Severe asthma is a difficult-to-control airway disease with pronounced heterogeneity in both clinical manifestations and underlying inflammatory mechanisms. This review examines the mechanisms, biomarkers, and biologic therapies of severe asthma, with a focus on biomarker-guided treatment selection and emerging precision strategies for type 2-high (T2-high) and type 2-low (T2-low) disease. The development of biologic therapies has changed the treatment paradigm, particularly for patients with T2-high inflammation. By targeting immunoglobulin E (IgE), interleukin-5 (IL-5), interleukin-4 receptor alpha (IL-4Rα), and thymic stromal lymphopoietin (TSLP)-related pathways, these agents can decrease exacerbations, improve lung function and symptom control, and enhance quality of life. Biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), total IgE, and sputum eosinophils, have been incorporated into clinical decision-making to support patient stratification. Emerging markers such as periostin, epithelial alarmins, gene-expression patterns, microRNAs, and multi-omics signatures are under investigation for more accurate phenotyping and response prediction. Despite these advances, current biomarkers do not always provide sufficient predictive accuracy, targeted options for T2-low asthma remain limited, biologics are costly, and long-term outcome data remain incomplete. Overall, integrating biomarker findings with clinical phenotype, comorbidities, and treatment history remains central to individualized biologic selection.

PMID:42714006 | DOI:10.3791/71404

J Vis Exp. 2026 Sep 8;(235). doi: 10.3791/71404.

ABSTRACT

Severe asthma is a difficult-to-control airway disease with pronounced heterogeneity in both clinical manifestations and underlying inflammatory mechanisms. This review examines the mechanisms, biomarkers, and biologic therapies of severe asthma, with a focus on biomarker-guided treatment selection and emerging precision strategies for type 2-high (T2-high) and type 2-low (T2-low) disease. The development of biologic therapies has changed the treatment paradigm, particularly for patients with T2-high inflammation. By targeting immunoglobulin E (IgE), interleukin-5 (IL-5), interleukin-4 receptor alpha (IL-4Rα), and thymic stromal lymphopoietin (TSLP)-related pathways, these agents can decrease exacerbations, improve lung function and symptom control, and enhance quality of life. Biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), total IgE, and sputum eosinophils, have been incorporated into clinical decision-making to support patient stratification. Emerging markers such as periostin, epithelial alarmins, gene-expression patterns, microRNAs, and multi-omics signatures are under investigation for more accurate phenotyping and response prediction. Despite these advances, current biomarkers do not always provide sufficient predictive accuracy, targeted options for T2-low asthma remain limited, biologics are costly, and long-term outcome data remain incomplete. Overall, integrating biomarker findings with clinical phenotype, comorbidities, and treatment history remains central to individualized biologic selection.

PMID:42714006 | DOI:10.3791/71404

Front Microbiol. 2026 Apr 28;17:1782471. doi: 10.3389/fmicb.2026.1782471. eCollection 2026.

ABSTRACT

Digestive system cancers (DSCs) represent a substantial global health burden. In recent years, the role of gut microbiota in the DSCs has garnered considerable attention, but its change pattern during tumor progression and the specific mechanisms are still not fully understood. We conducted a comprehensive systematic review to characterize patterns of gut microbiota dysbiosis across different DSC types and assess their clinical significance. We systematically searched four English and three Chinese databases up to January 2025 to identify systematic reviews focused on the dynamic characteristics of the gut microbiota during gastrointestinal tumorigenesis. Microbiota biodiversity and taxonomic composition were extracted to identify specific signatures associated with DSCs. The ROBIS tool was used to evaluate the methodological quality of the included studies. Ultimately, 59 studies involving six distinct DSC types were included. Data synthesis and comparison revealed distinct microbiota profiles across DSCs. At the phylum level, Bacillota was decreased in esophageal cancer (EC) and pancreatic ductal adenocarcinoma (PDAC), Pseudomonadota was augmented in EC but exhibited divergent trajectories in colorectal cancer (CRC) and PDAC. Genus-level analyses revealed Veillonella enrichment in EC and PDAC, and Fusobacterium outgrowth in EC, gastric cancer (GC) and CRC. Parvimonas and Streptococcus showed a concordant ascending trend in GC and CRC. Prevotella was overrepresented in EC and GC. This synthesis delineates a qualitative landscape of gut microbiota imbalances associated with various DSCs, highlighting the potential for these microbial shifts to serve as markers for early detection and targeted therapy. Multiomics integration and prospective cohort studies should be prioritized to accelerate clinical translation.

PMID:42131199 | PMC:PMC13161176 | DOI:10.3389/fmicb.2026.1782471

Environ Int. 2026 Mar 28;210:110212. doi: 10.1016/j.envint.2026.110212. Online ahead of print.

ABSTRACT

Microplastics (MPs) and nanoplastics (NPs) are pervasive environmental contaminants, raising concerns about their potential to cause inflammation, oxidative stress, and lung injury through respiratory toxicity. Due to their smaller size, larger surface area, and greater reactivity, NPs may pose a greater risk than MPs, yet size-dependent toxicity mechanisms remain unclear. This study investigates the distinct early molecular initiating events and toxicological effects of 1 μm polystyrene MPs (PS-MPs) and 20 nm polystyrene NPs (PS-NPs). Based on the internal exposure dose estimated from Py-GC/MS analysis, in vitro exposure concentrations were set at 0, 62.5, 125, 250, 500, and 1000 μg/mL. Multi-omics sequencing and integrative analysis identify specific proteomic and metabolomic alterations. Molecular dynamics simulations and co-immunoprecipitation assays elucidate binding interactions between PS-NPs-induced proteins and metabolic enzymes. In vitro and in vivo experiments reveal a greater accumulation of PS-NPs through endocytosis compared to PS-MPs; while pronounced histopathological damage with inflammatory response in mice lungs were only induced by PS-NPs, rather than PS-MPs. Compared to control group, PS-MPs partly caused proteomic or metabolomic perturbations, while PS-NPs induced significant differential expression of more extensive proteins and metabolites. PS-NPs exposure specifically upregulates insulin-like growth factor 2 receptor (IGF2R) expression and reduces Hypoxanthine levels when compared with PS-MPs. IGF2R directly interacts with Hypoxanthine-guanine phosphoribosyl transferase (HPRT), a key enzyme in Hypoxanthine metabolism, causing its disruption. This study provides important insights into the comparative toxic effects between PS-NPs with PS-MPs, especially the unique toxicological mechanisms of PS-NPs, thereby advancing the understanding of airborne plastic pollutant risks and supporting future regulatory assessments.

PMID:41921402 | DOI:10.1016/j.envint.2026.110212