Free Radic Biol Med. 2026 Sep 9;256:441-460. doi: 10.1016/j.freeradbiomed.2026.09.006. Online ahead of print.

ABSTRACT

Gestational diabetes mellitus (GDM) is a common pregnancy complication with a rising global prevalence, posing serious short-term and long-term health threats to both mothers and offspring. This review repositions GDM as a systemic disorder in which oxidative stress acts as a proposed mechanistic hub, linking upstream risk factors to downstream pathophysiology. We first examine how "upstream" factors-including genetic susceptibility, pre-conception status, and environmental exposures-converge to promote a state of pathological redox imbalance. We then examine key mechanistic pathways through which oxidative stress is thought to contribute to systemic insulin resistance and pancreatic β-cell failure, highlighting novel pathways involving intercellular communication via tunneling nanotubes and exosomes. Furthermore, we explore the downstream cascade, where oxidative stress may program maternal accelerated biological aging and multi-organ offspring disease trajectories through nuclear epigenetic programming and mitochondrial dysfunction programming, leaving what has been termed a persistent "metabolic memory". Consequently, this review evaluates emerging strategies that target oxidative stress for early prediction and precision intervention. Early prediction models based on direct redox biomarkers and multi-omics signatures hold potential to shift diagnosis from late-gestation oral glucose tolerance test (OGTT) to first-trimester risk stratification. Current supporting evidence draws from human epidemiological associations, ex vivo placental analyses, and experimental models. However, direct causal and interventional validation in pregnant women remains limited. Integrating targeted redox risk stratification and precision interventions into a life-course clinical framework may help interrupt the intergenerational transmission of metabolic disease initiated by GDM.

PMID:42716407 | DOI:10.1016/j.freeradbiomed.2026.09.006

Chin J Cancer Res. 2026 Aug 30;38(4):480-500. doi: 10.21147/j.issn.1000-9604.2026.04.08.

ABSTRACT

OBJECTIVE: Breast cancer remains a leading cause of global cancer mortality, characterized by profound heterogeneity. While immune checkpoint blockade (ICB) has transformed oncology, its efficacy in breast cancer is often hindered by "immune-cold" microenvironments and immune exclusion. Programmed cell death (PCD) is a critical regulator of tumor immune microenvironment (TIME). However, its role in the breast cancer immune microenvironment remains poorly understood.

METHODS: We integrated multi-omics data from six breast cancer cohorts (N=3,764) to develop a programmed cell death learning signature (PCDsig) using over 100 machine learning combinations. The model was benchmarked against 29 published signatures. Single-cell transcriptomic analysis decoded the immune landscape and cellular crosstalk. The role of adaptor-related protein complex 1 subunit sigma 1 (AP1S1) was validated through a clinical cohort, in vitro functional assays, and in vivo syngeneic mouse models.

RESULTS: PCDsig significantly stratified patient prognosis across all cohorts, consistently outperforming 29 existing models. High PCDsig scores correlated with immune-excluded phenotypes, reduced CD8+ T cell infiltration, and lower immunophenoscores. Single-cell analysis revealed that high-PCDsig tumors utilize vascular endothelial growth factor A (VEGFA) signaling to foster an immunosuppressive microenvironment. AP1S1 was identified as the core driver of immune exclusion. And our clinical cohort supported the immune exclusion effect of AP1S1. AP1S1 knockdown impaired tumor progression in vitro and fundamentally remodeled the tumor immune ecosystem in vivo. Combining AP1S1 inhibition with anti-programmed cell death ligand 1 (anti-PD-L1) therapy exerted profound synergistic effects, driven by massive infiltration and functional activation of cytotoxic Granzyme B (GZMB)+CD8+ T cells.

CONCLUSIONS: Our study establishes the PCDsig we developed is a potential prognostic and predictive biomarker for breast cancer. We provide the first evidence of AP1S1 as a core immunomodulatory oncogene that mediates immune exclusion. Targeting AP1S1 represents a highly promising strategy to sensitize cold breast tumors to ICB, offering a new perspective for precision immunotherapy.

PMID:42712842 | PMC:PMC13551362 | DOI:10.21147/j.issn.1000-9604.2026.04.08

Theranostics. 2026 Jul 29;16(15):8478-8500. doi: 10.7150/thno.131237. eCollection 2026.

ABSTRACT

BACKGROUND: The αvβ6 and αvβ8 integrins are upregulated in many solid-tumors and drive local activation of transforming growth factor-β (TGFβ), promoting immune evasion and resistance to immune checkpoint blockade. The chromogranin A-derived peptide 4Δ targets the RGD-binding site of αvβ6/αvβ8 and inhibits integrin-dependent TGFβ-activation. We investigated whether 4Δ-derived peptibodies can deliver cytotoxic drugs to cancer cells and enhance immune checkpoint inhibitors (ICIs) activity.

METHODS: Peptide 4Δ was genetically fused to the Fc domains of murine and human IgG1 to generate the peptibodies 4ΔmFc and 4ΔhFc. Integrin-binding properties and inhibition of TGFβ activation were characterized using biochemical and cell-based assays. Peptibody internalization and lysosomal trafficking were analyzed by live-cell/confocal microscopy. Cytotoxic activity of peptibodies complexed with anti-Fc antibodies coupled to anticancer drugs was evaluated using αvβ6/αvβ8-positive and -negative cancer cells. Pharmacokinetics and antitumor activity of 4ΔmFc, alone or in combination with an anti-PD-L1 antibody, were evaluated in murine fibrosarcoma and mammary carcinoma models.

RESULTS: 4ΔmFc and 4ΔhFc bound αvβ6 and αvβ8 with sub-nanomolar affinity. Both compounds selectively recognized αvβ6/αvβ8-positive tumor cells, as well as human pancreatic, lung, and colon carcinomas sections. 4ΔmFc and 4ΔhFc efficiently inhibited TGFβ activation, underwent efficient internalization, and trafficked to lysosomes. 4ΔhFc enabled delivery of cytotoxic payloads to αvβ6/αvβ8-positive cells, including MMAE, MMAF, DM1, PBD, or DX8951. 4ΔmFc delayed the growth of fibrosarcomas and improved mice survival in the mammary adenocarcinoma model when combined with an anti-PD-L1 mAb (immune checkpoint inhibitor), without overt toxicity.

CONCLUSION: These peptibodies represent a dual-selective αvβ6/αvβ8-targeting platform that couples potent blockade of integrin-dependent TGFβ activation with efficient, selective delivery of cytotoxic payloads to cancer cells. These properties, together with the observed synergism with anti-PD-L1 mAbs, suggest their potential use as ligands for delivering cytotoxic agents to tumors, while concomitantly modulating the TGFβ-driven immunosuppressive microenvironment, either alone or in combination with ICIs.

PMID:42708025 | PMC:PMC13549134 | DOI:10.7150/thno.131237

Gut. 2026 Sep 7:gutjnl-2025-337414. doi: 10.1136/gutjnl-2025-337414. Online ahead of print.

ABSTRACT

BACKGROUND: Neutrophils are increasingly recognised as immunosuppressive drivers of hepatocellular carcinoma (HCC), yet their persistence in the oxidative, lipid-rich tumour microenvironment remains poorly understood.

OBJECTIVE: To elucidate the metabolic and molecular programmes that enable tumour-associated neutrophils (TANs) to resist ferroptosis and sustain immunosuppression in HCC.

DESIGN: We employed human HCC samples, multiple murine HCC models, transcriptomic and lipidomic profiling, genetic loss-of-function systems and therapeutic interventions. Ferroptosis sensitivity, lipid metabolic rewiring and immunological consequences of TANs were systematically evaluated across models and validated in patient datasets and biospecimens.

RESULTS: TANs in human HCC and mouse models exhibit pronounced lipid accumulation and oxidative stress compared with peripheral neutrophils. Multi-omic profiling revealed that TANs are enriched for lipid-binding gene programmes and undergo rewiring towards sphingolipid and unsaturated fatty acid metabolism. We identified triggering receptor expressed on myeloid cells 2 (TREM2) as a key lipid-sensing receptor selectively expressed in TANs. Functional deletion of TREM2 reprogrammed the tumour immune microenvironment, restoring CD8⁺ T cell activity and suppressing HCC progression. Mechanistically, tumour-derived sphingosine-1-phosphate (S1P) activates TREM2, triggering nuclear factor erythroid 2-related factor 2 (NRF2)-mediated transcription of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), thereby promoting ferroptosis resistance. TREM2 expression is transcriptionally induced by granulocyte-macrophage colony-stimulating factor-signal transducer and activator of transcription 3 (GM-CSF-STAT3) signalling. Genetic deletion of TREM2, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated knockout of sphingosine kinase 1/2 (SPHK1/2) in tumour cells, or pharmacological inhibition of S1P synthesis disrupts this protective lipid-immune circuit, sensitises TANs to ferroptosis and restricts tumour growth. Therapeutically, a peptide-based TREM2 inhibitor reprogrammes TANs, restores CD8⁺ T cell function and enhances anti-programmed cell death protein 1 (PD-1) immunotherapy efficacy. Clinically, TREM2⁺ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are enriched in HCC tumours, correlate with SPHK1/2 expression and T cell dysfunction and associate with poor patient prognosis.

CONCLUSION: Our study uncovers the S1P-TREM2-NRF2 axis as a critical metabolic-immune circuit that preserves neutrophil survival and immunosuppressive function in HCC. Targeting this lipid-dependent ferroptosis resistance pathway offers a promising therapeutic strategy to overcome immunotherapy resistance in liver cancer.

PMID:42705697 | DOI:10.1136/gutjnl-2025-337414

Phytomedicine. 2026 Aug 26;161:158760. doi: 10.1016/j.phymed.2026.158760. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) harbors TP53 mutations at high frequency, yet therapeutic strategies that specifically target mutant p53 remain limited.

PURPOSE: This study aimed to identify S100A6, a calcium-binding protein frequently upregulated in TP53-mutant PDAC, as a critical regulator of mutant p53 stability and tumor progression, and to explore potential S100A6-targeting agents for therapeutic intervention.

METHODS: We integrated computer-assisted drug screening with transcriptomics, acetylation omics, and molecular biology techniques to identify Agrimol B (AgrB), a bioactive compound derived from the traditional Chinese herb Agrimonia pilosa Ledeb., as a potential S100A6-targeting agent.

RESULTS: High S100A6 expression was closely associated with poor prognosis in patients with TP53-mutant PDAC, whereas S100A6 depletion markedly suppressed PDAC cell growth and metastatic potential. Mechanistically, AgrB enhanced the interaction between S100A6 and the deacetylase HDAC2, leading to reduced acetylation of mutant p53 at lysine 382. This disruption activated autophagy-dependent cell death and thereby inhibited PDAC progression.

CONCLUSION: Our findings reveal an S100A6-HDAC2-mutant p53 acetylation axis that regulates TP53-mutant pancreatic tumorigenesis, providing mechanistic evidence supporting S100A6 as a therapeutic vulnerability and highlighting AgrB as a promising natural-product-derived candidate for further development against this aggressive malignancy.

PMID:42700714 | DOI:10.1016/j.phymed.2026.158760

Anticancer Agents Med Chem. 2026 Aug 24. doi: 10.2174/0118715206400800251128055423. Online ahead of print.

ABSTRACT

Gastrointestinal (GI) cancers-including colorectal, gastric, pancreatic, and esophageal malignancies- remain among the most prevalent and lethal cancers worldwide, largely due to their biological complexity and late-stage diagnosis. This narrative review examines the critical role of biomarkers in advancing personalized treatment strategies for GI cancers. Key diagnostic, prognostic, and predictive biomarkers, such as KRAS, HER2, PD-L1, microsatellite instability (MSI), and circulating tumor DNA (ctDNA), are discussed about their application in clinical decision-making. The review highlights biomarker-driven approaches across different GI cancer types, demonstrating how molecular profiling informs early detection, treatment selection, and monitoring of therapeutic response. Recent technological advances-including liquid biopsy, next-generation sequencing, and multi-omics integration- have expanded biomarker discovery and enhanced clinical utility. Challenges in implementing biomarker testing, such as variability in expression, lack of standardization, and limited accessibility, are also addressed. Overall, this article emphasizes the transformative potential of biomarkers to tailor therapy, improve patient outcomes, and shape the future of precision oncology in gastrointestinal cancers.

PMID:42693869 | DOI:10.2174/0118715206400800251128055423

Nat Commun. 2026 Aug 7;17(1):9491. doi: 10.1038/s41467-026-76495-3.

ABSTRACT

Cancer-associated fibroblasts comprise diverse functionally distinct cellular subsets, with certain subpopulations exerting pivotal influence in shaping the pancreatic cancer immune microenvironment. Here we show that Lin28b⁺ cancer-associated fibroblasts contribute to establishing an immunologically cold tumor microenvironment in pancreatic ductal adenocarcinoma. Mechanistically, Lin28b directly binds to STING mRNA and promotes its degradation, thereby suppressing STING expression and downstream type I interferon signaling. Loss of Lin28b in cancer-associated fibroblasts activates the cGAS-STING-interferon signaling cascade, enhancing dendritic cell antigen presentation and CD8⁺ T cell cytotoxic function. Importantly, genetic inhibition of Lin28b in cancer-associated fibroblasts enhances sensitivity to anti-PD-L1 immune checkpoint blockade therapy. These findings reveal that targeting the Lin28b-STING axis represents a promising therapeutic strategy for overcoming the intrinsic resistance of pancreatic ductal adenocarcinoma to immunotherapy.

PMID:42693143 | PMC:PMC13542369 | DOI:10.1038/s41467-026-76495-3

Signal Transduct Target Ther. 2026 Sep 4;11(1):363. doi: 10.1038/s41392-026-02936-6.

ABSTRACT

Metabolic reprogramming forms the foundation of immune effector functions and the regulation of inflammation. As a pivotal node connecting the tricarboxylic acid cycle to immune signaling, the IRG1/ACOD1 and itaconate axes play a central role in coordinating inflammatory tone and redox balance. Itaconate, generated through the decarboxylation of cis aconitate, acts as an immunometabolic brake that engages multiple regulatory pathways to sustain the dynamic equilibrium between inflammation and tissue homeostasis. Across a broad spectrum of pathological conditions, including infectious diseases, metabolic disorders, ischemia‒reperfusion injury, neurodegenerative diseases, autoimmune disorders, and cancers, itaconate and its derivatives generally exert anti-inflammatory and cytoprotective effects. However, within specific microenvironments, these molecules may also be exploited by pathogens to evade immune clearance or promote immunosuppressive and protumorigenic responses. Future studies should further elucidate tissue- and lineage-specific functions, define bidirectional regulatory mechanisms, and optimize the pharmacokinetic properties of itaconate derivatives. With the advancement of multiomics integration, systems immunology, rational drug design, and engineered itaconate delivery technologies, the IRG1/ACOD1-itaconate axis and derivative-based therapeutic strategies are poised to emerge as key metabolic checkpoints and therapeutic targets in inflammatory-, metabolic-, immune-, and cancer-related diseases.

PMID:42693110 | PMC:PMC13542262 | DOI:10.1038/s41392-026-02936-6

World J Microbiol Biotechnol. 2026 Sep 3;42(9):514. doi: 10.1007/s11274-026-05249-6.

ABSTRACT

Obesity, Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) represent interconnected global health problems that can be caused by dietary factors, life-style changes and alterations in the gut microbiota composition. While numerous reports highlight the connections between microbial taxa and the host diseases, the underlying molecular mechanisms behind the impact of metabolites on the disease development remain poorly defined. In this review, the connection between four interrelated pathways through which metabolites from the gut microbiota affect metabolic disease are highlighted. They include (i) reprogramming of host metabolism through histone deacetylase (HDAC) inhibition and remodeling of the chromatin structure; (ii) mitochondrial dysfunction and disturbance in redox balance; (iii) hijacking of receptors and pathway biased crosstalk (FFAR2/3, GPR109A, FXR, TGR5, AhR, TLR4) and (iv) disruption of intestinal barrier and induction of metabolic endotoxemia. Such axes form a feedback network through which the inflammation and insulin resistance spread over the entire gut-adipose-liver-pancreas-muscle axis. The effect of the metabolites is very context-dependent since it relies on the concentration threshold, receptor bias, disease state and interaction between the host genotype and enterotype. The translational applications include composite metabolite biomarkers, enterotype-based therapeutic approaches, bacterial extracellular vesicles and machine learning approaches to develop multi-omics data analysis resulting in generation of a digital twin model.

PMID:42690471 | DOI:10.1007/s11274-026-05249-6

Hematol Oncol Clin North Am. 2026 Oct;40(5):807-829. doi: 10.1016/j.hoc.2026.05.021.

ABSTRACT

Precision medicine is used to treat gastrointestinal malignancies including esophageal, gastric, small bowel, colorectal, and pancreatic cancers. Cutting-edge assays to detect and treat these cancers are active areas of research and will soon become standard of care. Colorectal cancer is a prime example of precision oncology as disease site is no longer the final determinate of treatment. Here, the authors describe how leveraging an understanding of tumor biology translates to individualized patient care using evidence-based practices.

PMID:42686330 | DOI:10.1016/j.hoc.2026.05.021

J Vis Exp. 2026 Sep 1;(235). doi: 10.3791/73747.

ABSTRACT

Liver resection and liver transplantation remain cornerstone treatments for many hepatobiliary diseases, yet postoperative infection, impaired liver regeneration, and post-hepatectomy liver failure (PHLF) remain serious complications. Perioperative stressors can disrupt the gut-liver axis by altering the intestinal microbiota, epithelial barrier integrity, microbial metabolites, bile acid signaling, and host immunity. This review examines how these alterations relate to clinical outcomes and evaluates evidence for microbiota-targeted interventions, including probiotics, synbiotics, nutritional optimization, antibiotic stewardship, bile acid modulation, and emerging multiomics strategies. We distinguish liver resection from living-donor and deceased-donor liver transplantation because the patient populations, graft or remnant anatomy, ischemia-reperfusion exposures, immune status, and outcome definitions differ. Clinical evidence most consistently supports selected pro-/synbiotic strategies for reducing postoperative infection in higher-risk settings, whereas microbiome-based prediction of PHLF, fecal microbiota transplantation (FMT), bile acid-directed therapy, and precision multiomics-guided pathways remain investigational. Future work should use transparent literature identification, standardized perioperative protocols, risk-defined populations, external validation, and prospective multicenter trials. A better understanding of gut-liver interactions may help preserve beneficial host-microbial signals while limiting translocation and inflammation during recovery.

PMID:42683887 | DOI:10.3791/73747

Front Immunol. 2026 Aug 18;17:1904638. doi: 10.3389/fimmu.2026.1904638. eCollection 2026.

ABSTRACT

BACKGROUND: Aberrant tissue repair and relentless fibroblast activation are hallmark features of idiopathic pulmonary fibrosis (IPF). Although IPF and Alzheimer's disease (AD) share underlying aging-related pathologies, including immune and metabolic dysregulation, the putative genetic mechanisms linking AD susceptibility to pathogenic macrophage remodeling in the fibrotic niche are not fully established.

METHODS: We performed a two-sample Mendelian randomization (MR) analysis to assess the genetic association and potential causal relationship between AD and IPF. Shared hub genes were identified via protein interaction networks. To characterize macrophage heterogeneity and intercellular crosstalk within the IPF microenvironment, we interrogated scRNA-seq data (GSE122960) utilizing Monocle 3 and CellChat algorithms. The functional essentiality of APOE was evaluated bridging computational virtual knockout (scTenifoldKnk) with laboratory in vitro assays. Specifically, downstream transcriptomic shifts and fibroblast activation capacities were validated using APOE-silenced THP-1 macrophages and a Transwell co-culture model with MRC-5 cells.

RESULTS: MR estimates indicated that genetic liability to AD is associated with a lower risk of developing IPF. Integrated profiling identified the lipid-metabolism gene APOE as a central hub, specifically enriched in lung macrophages. Pseudotime modeling captured a pathogenic bifurcation in IPF, where macrophages evolve toward a terminal state marked by profound oxidative phosphorylation defects and massive SPP1 secretion. These SPP1+ macrophages primarily activate fibroblasts via CD44 and integrin signaling axes. Furthermore, both virtual simulations and in vitro THP-1 experiments demonstrated that loss of APOE function triggers the hyperactivation of complement (C1QA) and antigen-presentation (HLA-DR) pathways. Co-culture assays ultimately confirmed that APOE ablation in macrophages strongly exacerbates myofibroblast differentiation (elevated α-SMA and collagen I) in adjacent MRC-5 cells.

CONCLUSION: APOE functions as a vital metabolic barrier against pro-fibrotic macrophage polarization in the lung. Disruption of this specific lipid metabolic network is strongly associated with SPP1-driven fibroblast activation and local immune imbalance, providing a theoretical framework that strictly warrants future in vivo investigation to determine its clinical relevance.

PMID:42682427 | PMC:PMC13529525 | DOI:10.3389/fimmu.2026.1904638

Life Sci Alliance. 2026 Sep 1;9(11):e202603840. doi: 10.26508/lsa.202603840. Print 2026 Nov.

ABSTRACT

In periods of sustained hyper-nutrition, pancreatic β-cells undergo functional compensation through transcriptional upregulation of gene programs driving insulin secretion. This adaptation is essential for maintaining systemic glucose homeostasis and metabolic health. Using single nuclei multiomics, we have mapped the early transcriptional adaptive mechanisms in murine islets of Langerhans exposed to high-fat diet (HFD) for 1 and 3 wk. We show that β-cells exhibit the largest transcriptional response to HFD, characterized by early activation of pro-inflammatory eRegulons and down-regulation of β-cell identity genes, particularly in a distinct subset of β-cells. These observations extend to humans, where the prevalence of an β-cells with a high inflammatory signature is increased in diabetes. Collectively, these observations point to cellular crosstalk through pro-inflammatory signaling as a central and early driver of β-cell dysfunction that limits the compensatory capacity of β-cells, which is closely linked to the development of diabetes.

PMID:42680559 | PMC:PMC13534335 | DOI:10.26508/lsa.202603840

J Hazard Mater. 2026 Sep 15;516:143449. doi: 10.1016/j.jhazmat.2026.143449. Epub 2026 Aug 30.

ABSTRACT

The global incidence of ulcerative colitis (UC) has significantly increased in rapidly industrializing nations, with numerous studies highlighting environmental exposures, particularly nitrogen dioxide (NO₂), as potential contributors to disease susceptibility. However, the clinical implications and molecular mechanisms linking NO₂ exposure to UC susceptibility remain poorly understood. This study investigated the associations between NO₂ and UC by integrating multi-omics data. We identified a CD8⁺ T cell subpopulation with a distinct phenotype characterized by perforin production, which potentially exacerbated colonic inflammation related to NO₂ exposure. To validate this hypothesis, we established mouse models exposed to NO₂, confirming increased CD8⁺ T cell infiltration and elevated perforin secretion through immunofluorescent (IF) staining. Employing artificial intelligence techniques, we identified Cell Division Cycle 25B (CDC25B) as a gene of interest correlated with putative NO₂-related UC signatures. Finally, through molecular docking (MD) and molecular dynamics simulations (MDS), we identified ozanimod as one of several computationally nominated compounds associated with the CDC25B‑related network; however, none of these computational predictions were experimentally validated in the present study. Collectively, these findings suggest a correlative link between perforin or CD8⁺ T cell-associated colonic inflammation and NO₂-associated UC susceptibility, and nominate CDC25B as a candidate gene for further investigation.

PMID:42679583 | DOI:10.1016/j.jhazmat.2026.143449

Immunobiology. 2026 Aug 28;231(5):153239. doi: 10.1016/j.imbio.2026.153239. Online ahead of print.

ABSTRACT

Chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) frequently coexist, yet distinguishing inflammatory changes secondary to malignancy from primary pancreatitis remains challenging. Here, we present an integrated multi-omics analysis of spatially distinct pancreatic tissue compartments obtained from a single patient undergoing pancreaticoduodenectomy for PDAC, combining histopathology, transcriptomics, immunofluorescence, and meta-transcriptomic microbial profiling. Morphological assessment identified tumor tissue, adjacent CP, and normal pancreas. Transcriptomic profiling of macro-dissected samples revealed differential gene expression and enrichment of the classical complement pathway in the CP compartment, which was qualitatively supported by immunofluorescent detection of C1q and C3 along the ductal epithelium. Meta-transcriptomic analysis detected a limited number of bacterial taxa and no viral RNA; these findings were interpreted conservatively given the constraints of low-biomass tissue profiling and the single-patient design. Although causal inference and generalizability are limited by the single-patient design, this study demonstrates the feasibility of integrating pathology with transcriptomic and microbial analyses to generate a hypothesis-generating, multi-omics framework for exploring inflammatory-malignant interactions in pancreatic disease.

PMID:42679433 | DOI:10.1016/j.imbio.2026.153239