Front Cell Infect Microbiol. 2026 Mar 16;16:1793213. doi: 10.3389/fcimb.2026.1793213. eCollection 2026.

ABSTRACT

The progression from cirrhosis to hepatocellular carcinoma (HCC) is a key outcome in the management of chronic liver disease. This process has a long incubation period and significant individual differences, making early warning still difficult. Clinical follow-up mainly relies on imaging examinations and alpha fetoprotein, but the ability to identify high risk precancerous states is limited. The imbalance of gut microbiota and its metabolites may occur earlier than the visible stage of tumors. They can affect barrier integrity, chronic inflammation, immune surveillance, and metabolic homeostasis through the gut liver axis, and participate in the formation of a pro tumor microenvironment. Therefore, such changes may provide more upstream risk stratification clues for the population with cirrhosis. This article summarizes previous research evidence and summarizes the common microbiome and metabolite characteristics of cirrhosis and high-risk populations, including a decrease in short chain fatty acid (SCFA) related symbiotic bacteria, an increase in inflammation related bacteria, bile acid spectrum shift, and other intestinal derived metabolite abnormalities. This article also outlines the key mechanisms that these features may correspond to, such as barrier damage and microbial translocation, immune suppression, etc. There are still significant uncertainties at present. The effect of SCFA is context dependent. Different etiologies, diets, medications, and complications can lead to significant confounding and affect cross cohort consistency. Subsequent research requires longitudinal cohort validation and the promotion of multi omics integration and the construction of interpretable predictive models to support clinical translation.

PMID:41918873 | PMC:PMC13033666 | DOI:10.3389/fcimb.2026.1793213

Front Immunol. 2026 Mar 16;17:1822612. doi: 10.3389/fimmu.2026.1822612. eCollection 2026.

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2026.1782545.].

PMID:41918731 | PMC:PMC13033988 | DOI:10.3389/fimmu.2026.1822612

Front Pediatr. 2026 Mar 16;14:1770578. doi: 10.3389/fped.2026.1770578. eCollection 2026.

ABSTRACT

The neonatal lung, once considered sterile, is now recognized to harbor a dynamic and complex microbiome that plays a critical role in respiratory health and disease. This review synthesizes current evidence on the composition, development, and functional impact of the lung microbiome in neonates, with a focus on its involvement in key respiratory disorders such as bronchopulmonary dysplasia, respiratory syncytial virus infection, neonatal acute respiratory distress syndrome, cystic fibrosis, and asthma predisposition. We place particular emphasis on the bidirectional communication along the gut-lung axis as a central mechanism, wherein intestinal microbiota and their metabolites modulate pulmonary immunity and inflammation. Emerging multi-omics studies that integrate microbial data with host metabolomic and immune profiles are highlighted for their role in deciphering disease-specific dysbiotic signatures and mechanistic pathways. Critically, this review advances the discussion beyond association by evaluating the translational potential of the microbiome as both a diagnostic biomarker and a therapeutic target. We provide a critical appraisal of innovative microbiome-targeted strategies-including probiotics, postbiotics, phage therapy, and bacterial lysates-and discuss the unique challenges and future directions for translating these approaches into safe, effective clinical interventions for vulnerable neonates. By bridging foundational science with clinical implications, this work aims to inform the development of novel, ecology-informed therapeutics to prevent and mitigate neonatal respiratory diseases.

PMID:41918694 | PMC:PMC13033698 | DOI:10.3389/fped.2026.1770578

NPJ Precis Oncol. 2026 Mar 31. doi: 10.1038/s41698-026-01394-1. Online ahead of print.

ABSTRACT

VDAC2's known role in cancer and immune regulation via enhancing the CD8⁺ T cell-mediated killing, and it is worth systematically digging out the role of VDAC2 in pan-cancer based on this research. Bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomic analyses were utilized to explore the role of VDAC2 from multiple perspectives in pan-cancers. RT-PCR, cell co-culture, CCK-8 assay, Transwell invasion assays, and ELISA were performed to validate the expression level and biological function. VDAC2 was upregulated in the majority of pan-cancers, and functional enrichment analyses displayed that VDAC2 may take part in the biological progress of energy metabolism, mitochondrial damage and cell proliferation. The landscape of VDAC2 expression and immune infiltration was constructed, and the VDAC2-BAK1-IFNγ pathway was identified in digestive cancer. VDAC2 had the potential to serve as a novel prognostic, screening cancer indicator and immune therapeutic target sensitive to various drugs. Overexpression of VDAC2 significantly promoted gastric cancer cell proliferation, invasion and immune invasion, as validated in vitro experiments. In short, our pan-cancer analysis constructed a comprehensive landscape of VDAC2's oncogenic role, establishing VDAC2 + -BAK1-IFNγ as an important pathway in tumor progression and immune evasion. VDAC2 emerges not only as a valuable prognostic biomarker but also as a promising novel therapeutic target.

PMID:41917254 | DOI:10.1038/s41698-026-01394-1

Cancer Immunol Immunother. 2026 Mar 31;75(4):126. doi: 10.1007/s00262-026-04368-1.

ABSTRACT

While anti-programmed death-1 (anti-PD-1) therapy has revolutionized lung cancer treatment, its efficacy remains limited by an immunosuppressive tumor microenvironment (TME). We therefore investigated whether combining anti-PD-1 inhibitor with catgut embedding at the Zusanli acupoint (CIAA) could enhance anti-tumor immunity by reprogramming the TME in a lung cancer mouse model. Combining in vivo tumor monitoring, multi-parametric immune profiling (flow cytometry, IHC, ELISA), and multi-omics analyses (transcriptomics and metabolomics), we found that the combination therapy was associated with enhanced tumor growth inhibition. This effect correlated with a comprehensive TME transformation: conversion to an immunologically active state with increased effector immune cell infiltration (CD8⁺ T, CD4⁺ T, B cells, macrophages) and decreased regulatory T cells, coupled with suppression of pro-tumorigenic factors (VEGF, IL-6). Integrated omics analysis suggests that the combined treatment may modulate tumor-stroma interaction pathways (e.g., PI3K-Akt, focal adhesion) and rewire immunometabolic networks (e.g., tryptophan metabolism). Our study provides hypothesis-generating correlative data positioning CIAA as a potential adjunct capable of remodeling the TME to potentiate anti-PD-1 therapy in lung cancer.

PMID:41915222 | DOI:10.1007/s00262-026-04368-1

Food Funct. 2026 Mar 31. doi: 10.1039/d5fo04958j. Online ahead of print.

ABSTRACT

The probiotic yeast Saccharomyces boulardii is renowned for its clinical efficacy, which is intrinsically linked to its exceptional ability to survive the harsh gastrointestinal (GI) environment. However, a comprehensive understanding of the molecular mechanisms and regulatory pathways underlying the stress tolerance of S. boulardii remains limited. This study employed an integrated transcriptomic and proteomic approach to systematically map the dynamic responses of S. boulardii to simulated GI transit. Our analysis revealed that the intestinal phase posed a significantly greater challenge than the gastric phase, triggering extensive molecular reprogramming. A core adaptive strategy was the marked upregulation of the central carbon metabolism, particularly glycolysis, as evidenced by the concerted overexpression of key enzymes at both transcriptional and translational levels, indicating a heightened demand for energy to fuel stress defence mechanisms. Furthermore, significant enrichment was observed in the pathways related to nitrogen and fatty acid metabolism. Integration of the multi-omics datasets highlighted the complexity of the regulatory response, with frequent discordance between mRNA and protein abundance underscoring the importance of post-transcriptional regulation. This study provides a detailed molecular profile of the stress tolerance network in S. boulardii, elucidating the strategic metabolic rewiring and multi-layered regulation that underpin its probiotic resilience. The findings offer valuable insights and a foundational resource for the future development of enhanced probiotic therapies.

PMID:41914832 | DOI:10.1039/d5fo04958j

Zhonghua Yi Xue Za Zhi. 2026 Mar 31;106:1-7. doi: 10.3760/cma.j.cn112137-20251201-03143. Online ahead of print.

ABSTRACT

Objective: To analyze the association between molecular typing and prognosis with recurrence pattern in triple-negative breast cancer (TNBC) patients based on long-term follow-up of a multi-omics cohort. Methods: A retrospective analysis was performed on the clinical data and transcriptomic data of patients diagnosed with TNBC at Department of Breast Surgery, Fudan University Shanghai Cancer Center from January 1, 2007, to December 31, 2014. The survival status of patients was documented, and the follow-up continued until the patients' death or August 31, 2025. According to the"Fudan subtype", the patients were categorized into the basal-like immune suppressed (BLIS), immunomodulatory (IM), luminal androgen receptor (LAR), and mesenchymal-like (MES). Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was employed to evaluate the differences in overall survival (OS), disease-free survival (DFS) and recurrence-free interval (RFI) among TNBC patients with different molecular subtypes. Multivariate Cox proportional hazards regression analysis was used to assess the association between"Fudan subtype"and OS, DFS and RFI. Differential expression analysis and subsequent gene set enrichment were conducted. Competing-risk models were used to calculate the cumulative incidence of lung metastasis after accounting for competing events, and the differences were assessed using the Fine-Gray test. Results: After excluding 9 patients lost to follow-up, a total of 351 patients with TNBC were included in the analysis. The mean age at baseline was 53.46±11.36 years, and the median follow-up duration was 102.09 months. During follow-up, 72 patients died and 84 experienced recurrence or metastasis. Among them, 134 patients were classified as the BLIS subtype, with 27 deaths (20.15%); 86 patients were classified as the IM subtype, with 11 deaths (12.79%); 81 patients were classified as the LAR subtype, with 22 deaths (27.16%); and 50 patients were classified as the MES subtype, with 12 deaths (24.00%). The 10-year RFI rates for the BLIS, IM, LAR, and MES subtypes were 80.12% (95%CI: 73.41%-87.44%), 92.35% (95%CI: 86.64%-98.43%), 81.92% (95%CI: 73.39%-91.44%), and 72.95% (95%CI: 61.37%-86.71%), respectively. Kaplan-Meier survival curves showed that the differences of RFI among the four molecular subtypes of patients were statistically significant (P=0.040). Multivariate analysis showed that LAR subtype (LAR vs IM, HR=2.41, P=0.042) was the independent risk factor for DFS, and BLIS subtype (BLIS vs IM, HR=4.17, P=0.011), LAR subtype (LAR vs IM, HR=3.49, P=0.040) and MES subtype (MES vs IM, HR=3.98, P=0.019) were independent risk factors for RFI. The BLIS subtype is more likely to develop recurrence or metastasis in the early postoperative period, particularly lung metastasis. Differential gene expression analysis showed that BLIS subtype-specific genes, including those involved in proliferation and cell cycle activity, were predominantly upregulated in tumors with early recurrence or metastasis. Competing-risk analysis demonstrated that BLIS patients had a higher cumulative incidence of lung metastasis both overall and within the first 5 years after surgery compared with non-BLIS patients (both P<0.05). Conclusion: The"Fudan subtype"was significantly associated with RFI in early-stage TNBC patients. In addition, recurrence and metastasis were more likely to be observed in the early postoperative period in the BLIS subtype, particularly early lung metastasis.

PMID:41913624 | DOI:10.3760/cma.j.cn112137-20251201-03143

EMBO Mol Med. 2026 Mar 30. doi: 10.1038/s44321-026-00410-y. Online ahead of print.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

PMID:41912871 | DOI:10.1038/s44321-026-00410-y

Nat Med. 2026 Mar 30. doi: 10.1038/s41591-026-04250-8. Online ahead of print.

ABSTRACT

Ischemic heart disease (IHD) remains a leading cause of death worldwide, with dietary risks being its most significant modifiable factor. Here, using the Global Burden of Diseases, Injuries and Risk Factors Study 2023, we estimated the mortality and disability-adjusted life years from diet-related IHD across 204 countries. In 2023, a suboptimal diet was responsible for 4.06 million (95% uncertainty interval (UI) 0.74-6.22) IHD deaths and 96.84 million (18.82-142.52) IHD disability-adjusted life years. The global age-standardized death rate of IHD attributable to suboptimal diet decreased by 43.92% (95% UI 34.44-53.23) per 100,000 population from 1990 to 2023. Among dietary factors, low intake of nuts and seeds (9.87, 95% UI 2.84-17.12 deaths per 100,000 population), low whole grains (9.22, 4.73-13.67), low fruits (7.25, 1.54-13.34) and high sodium (7.15, 0.92-17.97) were primary contributors to IHD deaths. The burden was particularly pronounced in low- and middle-sociodemographic index countries. By disentangling dietary risk factors, we identified the portion of IHD burden directly modifiable through food interventions.

PMID:41912805 | DOI:10.1038/s41591-026-04250-8

Nat Commun. 2026 Mar 30. doi: 10.1038/s41467-026-71196-3. Online ahead of print.

ABSTRACT

Exposure to airborne fine particulate matter (PM_2.5) has been linked to increased risk of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet the underlying mechanisms remain unclear. Here, by leveraging a fine-tuned foundation model of single-cell transcriptomics, we uncover shared transcriptional signatures between PM_2.5 exposure and SARS-CoV-2 infection. We further validate this association using population-level epidemiological analyses and perform genome-wide association studies (GWAS) to identify genetic variants that modulate infection risk under PM_2.5 exposure. In addition, we identify NPC1 as a key modulator involved in SARS-CoV-2 infection efficiency under virus-laden PM_2.5 exposure through integrative functional genomic analyses and in vitro experiments. Our findings suggest that PM_2.5 facilitates viral entry through an NPC1-modulated endo-lysosomal pathway, providing a mechanistic explanation for observed pollution-related susceptibility. By integrating artificial intelligence (AI)-guided transcriptomics, epidemiology, GWAS, functional genomics, and in vitro verification, our study elucidates how environmental and genetic factors jointly influence SARS-CoV-2 susceptibility. This work highlights how AI-assisted multi-omics integration systematically decodes the health impacts of environmental exposures from molecular to population levels and informs air quality policy and infectious disease preparedness.

PMID:41912520 | DOI:10.1038/s41467-026-71196-3

Curr Opin Gastroenterol. 2026 May 1;42(3):121-128. doi: 10.1097/MOG.0000000000001165. Epub 2026 Mar 6.

ABSTRACT

PURPOSE OF REVIEW: Discuss advances in genomics, metabolomics, and proteomics in steatotic liver disease.

RECENT FINDINGS: Common genetic variants in genes including PNPLA3, TM6SF2, and HSD17B13 are associated with risk of hepatic steatosis, metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) cirrhosis, and hepatocellular carcinoma. In contrast, variants in other genes such as GCKR are strongly associated with steatosis but much more weakly associated with advanced liver disease. The cirrhosis-associated variants typically drive steatosis through reduction of lipid export from the liver, potentially highlighting this mechanism as a driver of fibrosis though not ruling out alternative pathways. Alterations in amino acids, lipids, bile acids, and other metabolites have been observed in both MASLD and ALD reflecting insulin resistance, altered bile acid metabolism, and increased fatty acid flux and de novo lipogenesis (for MASLD) or mitochondrial dysfunction (for ALD). Also seen are characteristic changes in serum/plasma protein levels reflecting fibrosis, systemic inflammation, and hepatic synthetic function are also seen with MASLD and ALD. Predictive models incorporating genomics, metabolomic, and proteomic biomarkers may improve upon existing clinical models, but nearly all studies on this topic have been retrospective or post hoc.

SUMMARY: Genomics, metabolomics, proteomics, and multiomics may improve our understanding of disease pathophysiology. They may also have implications for clinical care, but further prospective studies are required to establish whether they provide sufficient benefit over clinical biomarkers to be routinely used.

PMID:41912348 | DOI:10.1097/MOG.0000000000001165

Cancer Lett. 2026 Mar 28:218465. doi: 10.1016/j.canlet.2026.218465. Online ahead of print.

ABSTRACT

Cancer remains a leading cause of death worldwide, with lineage plasticity emerging as a hallmark that drives therapy resistance and tumor progression by enabling cancer cells to alter identity and evade targeted therapies. Although genomic and transcriptomic aberrations correlate with lineage plasticity, the absence of scalable cross-cancer markers to rapidly identify plastic subtypes has limited predictive utility. Homeobox (HOX) genes encode transcription factors that define tissue identity through distinct expression patterns, or HOX codes, within specific lineages. By analyzing multi-omics data encompassing 39 HOX genes across more than 80,000 RNA-seq samples across 23 cancer types spanning 114 cancer subtypes, we found that HOX code expression robustly stratifies lineage-constrained and lineage-plastic states at a cross-cancer level. This framework revealed previously unrecognized lineage-plastic subtypes in prostate cancer, lung cancer, and acute myeloid leukemia (AML), each displaying distinct HOX code divergence compared to non-plastic counterparts. Differential expression analysis across these representative malignancies identified RUNX1T1 as a consistent regulator associated with HOX-defined plastic states. We validated RUNX1T1 upregulation in bulk and single-cell RNA-seq from extensive preclinical and clinical cohorts and demonstrated that RUNX1T1 is functionally required for lineage-plastic programs in prostate cancer models. AI-based structural modeling and co-immunoprecipitation established the NCOR/HDAC3 complex as a critical binding partner of RUNX1T1. CUT&RUN profiling revealed that RUNX1T1 remodels chromatin by globally reducing active enhancer marks, thereby repressing lineage-defining differentiation programs and reshaping HOX positional identity. Selective pharmacologic inhibition of HDAC3 or targeted gene silencing via lipid nanoparticles suppressed the growth of lineage-plastic cancer cells, uncovering a therapeutically actionable vulnerability. Together, these findings establish RUNX1T1 as a cross-lineage regulator of HOX code-defined plasticity and identify the RUNX1T1-HDAC axis as a targetable mechanism underlying cancer lineage plasticity.

PMID:41912135 | DOI:10.1016/j.canlet.2026.218465

Microb Pathog. 2026 Mar 28:108464. doi: 10.1016/j.micpath.2026.108464. Online ahead of print.

ABSTRACT

Despite the clinical application of Ophiopogon japonicus in idiopathic pulmonary fibrosis (PF), its key anti-fibrotic components and underlying mechanisms remain poorly defined. Using a bleomycin-induced murine PF model, we systematically compared the efficacy of the total extract (OJTE), polysaccharides (OJTP), saponins (OJTS), and flavonoids (OJTF). The active component was further investigated via integrated metagenomics and metabolomics (serum/feces) to decipher the gut-lung axis mechanism. All O. japonicus components attenuated lung injury and collagen deposition, with OJTP demonstrating the most potent efficacy (reducing lung hydroxyproline content by 42.12% (p < 0.01) compared to the model group). Multi-omics analysis revealed that OJTP remodeled the gut microbiota, notably enriching probiotic strains such as Muribaculaceae bacterium (log₂FC = 2.17) and Duncaniella muricolitica (log₂FC = 2.06), as well as the polysaccharide-utilizing species Prevotella sp. MGM2 (log₂FC = 2.79). Concomitantly, OJTP significantly altered host metabolism, upregulating key metabolites including urobilinogen (p < 0.0001) and 5-amino valeric acid betaine (5-AVAB, p < 0.002). These metabolites are implicated in porphyrin and amino acid metabolism, respectively. Correlation networks further established strong associations between these OJTP-modulated microbes and metabolites. Our study first identifies OJTP as the primary bioactive component of O. japonicus against PF. We propose a novel trans-organ mechanism wherein OJTP ameliorates PF via orchestrating a "gut microbiota-metabolite" axis, highlighting the therapeutic potential of targeting polysaccharide-probiotic synergy.

PMID:41912071 | DOI:10.1016/j.micpath.2026.108464

J Vis Exp. 2026 Mar 13;(229). doi: 10.3791/70383.

ABSTRACT

This study utilized a multi-omics and computational biology framework to investigate the therapeutic potential of the Traditional Chinese Medicine (TCM) formula Buti Huatan Tang (BTHTT) against chronic obstructive pulmonary disease (COPD). Significant physiological improvements were observed in a rat model following BTHTT intervention. Histological analysis showed a reversal of lung pathological damage, while biochemical assays, and transcriptomics confirmed the normalization of IL-1β and IL-1R2 levels. Additionally, metabolic profiling revealed that BTHTT corrected disruptions in T3 and T4 thyroid hormone levels. A negative correlation was observed between the IL-1β/IL-1R2 axis and these thyroid hormones, indicating that their regulation is associated with the formula's therapeutic effect. Beyond direct measurements, machine learning algorithms identified ten COPD signature genes from clinical databases. Pathway enrichment analysis suggests that BTHTT may act through cytokine-cytokine-receptor interactions and thyroid hormone synthesis pathways. Furthermore, while 283 components were identified in vivo, compounds such as tanshinone IIA and cryptotanshinone are currently considered candidate active substances. Their role as primary drivers is supported by a model in which they stably bind to IL-1R2; this inference is based on molecular docking and molecular dynamics (MD) simulations rather than direct experimental isolation. Overall, the data support a model in which BTHTT exerts a multi-target effect on COPD by modulating inflammation and metabolic homeostasis. This integrated approach provides a refined scientific basis for the clinical application of BTHTT and highlights specific pathways for future experimental validation.

PMID:41911070 | DOI:10.3791/70383

Gut. 2026 Feb 9;75(3):576-587. doi: 10.1136/gutjnl-2025-337506.

ABSTRACT

BACKGROUND: Current guidelines recommend a two-step approach for risk stratification of metabolic dysfunction-associated steatotic liver disease (MASLD), starting with Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE).

OBJECTIVE: To evaluate this approach for predicting advanced fibrosis and liver-related events (LREs) in patients with type 2 diabetes (T2D).

DESIGN: A prospective liver biopsy cohort of T2D patients with histologically confirmed MASLD from seven centres in China was used to assess diagnostic performance for advanced fibrosis. The international VCTE-Prognosis cohort, including T2D patients with MASLD who underwent VCTE at 16 centres in the USA, Europe and Asia, with longitudinal follow-up, was used to assess LREs, defined as hepatic decompensation or hepatocellular carcinoma.

RESULTS: 4781 participants were included. In the liver biopsy cohort (n=352; 22.2% with advanced fibrosis), applying LSM thresholds of <8 kPa and >12 kPa after FIB-4 classified patients into 63.4% low-risk, 9.4% intermediate-risk and 27.3% high-risk, with a correct classification rate of 71%. In the VCTE-Prognosis cohort (n=4429; median follow-up 51.3 (IQR 27.4-70.7) months), 140 (3.2%) patients developed LREs (110 (2.5%) with hepatic decompensation and 59 (1.3%) with hepatocellular carcinoma). The two-step approach classified 72.6%, 6.8% and 20.6% of patients into low-risk, intermediate-risk and high-risk groups, with corresponding 5-year cumulative LRE incidences of 0.7%, 0.9% and 11.8%. Refining classification of intermediate FIB-4 patients using LSM <10 kPa (low-risk) and >15 kPa (high-risk) reduced the intermediate-risk group to 5.6% while preserving predictive accuracy.

CONCLUSION: The non-invasive two-step approach of FIB-4 followed by LSM effectively stratifies MASLD-related advanced fibrosis and LREs risk in T2D. Applying LSM cut-offs of 10 and 15 kPa further optimises risk stratification for future LREs.

PMID:41911049 | DOI:10.1136/gutjnl-2025-337506

J Asthma Allergy. 2026 Mar 19;19:575312. doi: 10.2147/JAA.S575312. eCollection 2026.

ABSTRACT

Systems biology approaches have contributed to advancing our understanding of complex respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD). This systematic review evaluates the application of systems biology methodologies in respiratory medicine, focusing on multi-omics data integration and computational techniques for biomarker discovery and mechanistic understanding. Following PRISMA 2020 guidelines, we conducted a comprehensive literature search across Web of Science and Scopus databases, identifying 117 peer-reviewed documents published from 2010 to 2024. The review methodology employed bibliometric analysis combined with qualitative synthesis of included studies. Results demonstrate steady growth in systems biology applications for asthma and COPD research, with publication rates increasing by approximately 0.5 articles per year (R² = 0.73, p < 0.001). Bibliometric analysis identified five major research clusters: systems biology as a foundational methodological framework (Basic Theme), COPD-focused research as the most developed area (Motor Theme), gene expression analysis, disease classification approaches, and specialized lung disease investigations (Niche Theme). Multi-omics integration studies achieved 82-91% accuracy in disease classification tasks, with transcriptomics-based asthma endotyping validated in over 1500 patients across multiple cohorts. Network analysis approaches identified hub genes (IL-6, TNF-α, MMP9) replicated across three independent studies. Machine learning applications demonstrated 80-90% accuracy for diagnostic and prognostic tasks, though external validation remains limited, with only 15% of reviewed studies including independent validation cohorts. Significant challenges persist in data integration, computational reproducibility, and clinical translation. Most studies employed modest sample sizes (median n=89), and population diversity was limited, with 89% conducted in European-ancestry populations. This review provides a comprehensive assessment of systems biology progress in respiratory medicine, identifies methodological gaps, and highlights the need for standardized protocols, larger collaborative studies, and rigorous external validation to advance clinical implementation of systems biology findings in asthma and COPD management.

PMID:41878747 | PMC:PMC13007689 | DOI:10.2147/JAA.S575312

Cell Metab. 2026 Mar 23:S1550-4131(26)00087-2. doi: 10.1016/j.cmet.2026.02.018. Online ahead of print.

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting one-third of the global population. Most patients exhibit simple steatosis, whereas up to 20% develop metabolic dysfunction-associated steatohepatitis (MASH), potentially culminating in liver cirrhosis and hepatocellular carcinoma. Diverse parallel mechanisms contribute to the development of MASH, which are fueled by hepatic lipotoxicity, intestinal dysbiosis, and pro-inflammatory diets shaping innate and adaptive immune responses. Moreover, adipose tissue is driving systemic inflammation in obesity, contributing to the inflammatory burden in obesity-related MASH. Polygenetic and multiomic risk scores identify distinct types of MASLD with dominant aggressive liver disease or extrahepatic cardiometabolic disease. Here, we review the complexity of multiple parallel inflammatory hits in MASH and delineate that most current MASH drugs exert pleiotropic metabolic and anti-inflammatory properties. These new therapies will change the clinical management of this disease in the near future.

PMID:41875884 | DOI:10.1016/j.cmet.2026.02.018

Ecotoxicol Environ Saf. 2026 Mar 23;314:120063. doi: 10.1016/j.ecoenv.2026.120063. Online ahead of print.

NO ABSTRACT

PMID:41875554 | DOI:10.1016/j.ecoenv.2026.120063

Immunotherapy. 2026 Mar 24:1-13. doi: 10.1080/1750743X.2026.2648431. Online ahead of print.

ABSTRACT

The gut microbiota (GM) has emerged as a key modulator of cancer development and therapeutic response beyond the gastrointestinal tract. In extra-intestinal cancers, GM composition influences oncogenesis, with specific microbial taxa and their metabolites linked to either increased or decreased cancer risk, as highlighted by Mendelian Randomization studies. Beyond cancer initiation, GM plays a critical role in shaping the efficacy and toxicity of anticancer therapies, particularly immunotherapy. We searched PubMed and ClinicalTrials.gov using the terms"gut microbiota," "immune checkpoint inhibitors," "faecal microbiota transplantation," "solid tumor" in oncology patients. Evidence indicates that SCFA-producing bacteria, Akkermansia muciniphila, and members of Lachnospiraceae and Ruminococcaceae families enhance responses to immune checkpoint inhibitors (ICIs), whereas dysbiosis and immunosuppressive bacteria are associated with poor outcomes and immune-related adverse events. Therapeutic modulation of the GM through probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions shows promise in optimizing immunotherapy efficacy, yet standardized clinical protocols remain lacking. Integrating GM profiling with multi-omics and artificial intelligence approaches offers a path toward personalized microbiota-targeted interventions to improve patient outcomes. This review critically summarizes current evidence linking GM to cancer immunotherapy, discusses mechanistic insights, and outlines future perspectives for translating microbiota modulation into clinical practice.

PMID:41873461 | DOI:10.1080/1750743X.2026.2648431

Nat Commun. 2026 Mar 23. doi: 10.1038/s41467-026-70798-1. Online ahead of print.

ABSTRACT

Glioblastoma (GBM) remains a lethal brain tumor due to therapy resistance. While autophagy contributes to temozolomide (TMZ) resistance, its regulation is incompletely understood. This study investigates the role of replication factor RFC4, which is associated with poor prognosis and TMZ resistance in GBM. Multi-omics analyses and molecular experiments reveal that TMZ-induced chromatin accessibility enables transcription factor YY1 to bind the RFC4 promoter and upregulate its expression. RFC4, in turn, stabilizes the kinase STK38, which is essential for autophagosome formation. The RFC4-STK38 interaction facilitates BECN1 recruitment, thereby activating autophagy. Phosphorylation of STK38 at T444 stabilizes this complex, whereas a phospho-deficient mutant impairs autophagy. In vivo, RFC4 overexpression confers TMZ resistance, reversible by autophagy inhibition. Thus, our findings identify the RFC4-STK38-BECN1 axis as a mechanism underlying TMZ resistance and a potential target for precision therapy in GBM.

PMID:41872171 | DOI:10.1038/s41467-026-70798-1