PubMed Trending Research Digest — June 08, 2026

A curated digest of 100 trending PubMed articles, automatically categorised and summarised across 15 research areas.

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Asthma endotypes and airway biomarkers Lung cancer diagnosis, staging, and procedural advances Obesity and metabolic subphenotypes (including GLP-1/dual agonists) Genetic mechanisms and molecular stratification in rare GI disorders Mechanisms and evidence for manual/physical therapies Aging biology via iron, senescence, and ferroptosis Endoscopy and gastrointestinal procedural therapeutics Genetic risk and biomarkers in liver disease (MASLD/PBC/MASH) Tumor microenvironment and immune cell targeting in cancer Obesity-driven cancer biology and tumor microenvironment Neurodevelopmental disorders and synaptic/circuit mechanisms Clinical decision support and acute endocrine management Epilepsy mechanisms and targeted ion-channel therapy Infectious disease vaccines and host-pathogen mechanisms Cardiovascular prevention and cardiometabolic risk indices

Automated digest · 100 articles · 15 research areas · June 08, 2026

Overview

Across this week’s papers, a dominant theme is precision stratification—using biomarkers, genetics, and multi-omic signatures to identify which patients are likely to benefit from specific therapies. In asthma, T2-high endotypes split into allergic eosinophilic and non-allergic eosinophilic groups, supporting endotype-based treatment selection. In metabolic disease, multiple studies connect obesity subphenotypes to differential responses to incretin-based drugs (e.g., tirzepatide) and advance new GLP-1/dual-agonist regimens (cagrilintide-semaglutide, retatrutide, orforglipron, mazdutide, survodutide), while cohort work proposes practical risk indices (TyG-ABSI, CHG, AIPFI) for cardiovascular and cardiometabolic prevention.

A second major thread is mechanistic immunology and tumor microenvironment remodeling as a route to better cancer outcomes. Multi-omic profiling in colorectal liver metastasis highlights a TREM2+ lipid-laden immunosuppressive macrophage population at invasive margins, suggesting actionable targets to reverse metastatic immune suppression. Other studies emphasize how epigenetic regulators (BRD4), signaling axes (PAD4–IGF2BP2–MCM; SERPINE2–JAK2/STAT3–NRF2–GCLC), and microenvironmental cues (matrix stiffness via IQGAP3/SOX2) drive therapy resistance and progression. Complementing this, several works explore how to “heat up” immune responses—through cGAS–STING activation, macrophage immunometabolic reprogramming, or improved biomarker models for immunotherapy response.

Finally, the digest shows continued momentum in linking fundamental biology to clinical decision-making and safer interventions. Reviews and trials address procedural optimization (endoscopic hemostasis with self-assembling peptides; ventilation strategies during V-A ECMO; margin assessment in breast-conserving surgery), while mechanistic studies connect aging and neuroimmune pathways to disease: iron-driven lipid peroxidation and ferroptosis/senescence, calcium dysregulation triggering cGAS–STING–NF-κB inflammation, and microglial Galectin-3–TLR2/NLRP3 inflammasome signaling in sepsis-associated encephalopathy. Together, these studies reflect a broader shift toward therapies guided by causal pathways—measured with increasingly sophisticated biomarkers and multi-omic tools.

Asthma endotypes and airway biomarkers

Effects of inhaled nitric oxide on ventilation/perfusion mismatch assessed by electrical impedance tomography in intubated patients with moderate-to-severe ARDS: a prospective physiological study.

This prospective, single-center randomized controlled physiological study enrolled 40 mechanically ventilated adults with moderate-to-severe ARDS (PaO2/FiO2 ≤ 200 mmHg) to test whether inhaled nitric oxide (iNO) changes ventilation/perfusion (V/Q) matching and systemic inflammation over 24 hours. iNO was assessed using electrical impedance tomography alongside gas-exchange measures and inflammatory readouts. The trial design and measurements aim to clarify whether iNO’s oxygenation benefit in ARDS is mediated by improved V/Q matching and/or reduced inflammation.

Yu Y, Tian R, Zhang L et al. · Respiratory research · (2026) · View on PubMed ↗ · Free PDF ↗

Type 2 Endotypes in Airway Diseases.

This review studied type 2 (T2) endotypes in asthma and their relationship to biomarker-defined phenotypes in asthma patients. It found that more than half of asthma patients are T2-high and that T2-high asthma comprises allergic eosinophilic and non-allergic eosinophilic endotypes. These distinctions are clinically significant because they support more precise endotype-based stratification for airway disease management and therapy selection.

Maldonado A, Del Campo-Grijalba M, Angelina A et al. · Archivos de bronconeumologia · (2026) · View on PubMed ↗

The 2025 ATS/ERS update of the international multidisciplinary classification of the interstitial pneumonias: implications for the pathologist.

This review summarizes the 2025 ATS/ERS update to the international multidisciplinary classification of interstitial pneumonias and focuses on implications for pathologists. It highlights that, beyond the earlier 2002 and 2013 frameworks, newer advances include better distinction of idiopathic versus secondary disease, incorporation of molecular pathology, and recognition of progressive pulmonary fibrosis (PPF). The significance is improved diagnostic alignment between pathology and multidisciplinary clinical decision-making for interstitial pneumonias.

Nicholson AG, Cooper WA, Fabre A et al. · Histopathology · (2026) · View on PubMed ↗ · Free PDF ↗

Lung cancer diagnosis, staging, and procedural advances

Advances in Diagnosis-Pulmonology.

This review studied recent advances in pulmonology for lung cancer diagnosis and management, focusing on screening, bronchoscopy, and endoluminal approaches. It found that refinements in bronchoscopy and navigational bronchoscopy may enable a one-step diagnosis–staging–treatment workflow for early-stage lung cancer, alongside improved outcomes for malignant pleural effusions. The significance is that these diagnostic and procedural innovations could reduce invasiveness and accelerate treatment decisions in lung cancer care.

Stone E, Hu X, Afriyie-Mensah JS et al. · Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · (2026) · View on PubMed ↗

Obesity and metabolic subphenotypes (including GLP-1/dual agonists)

In the SYNCHRONIZE-MASLD phase 3 randomized, double-blind, placebo-controlled trial, 216 adults with obesity and at-risk metabolic dysfunction-associated steatotic liver disease (MASLD/MASH) were treated with once-weekly survodutide. Survodutide improved outcomes relevant to obesity and MASLD compared with placebo in this population. The results position survodutide as a potential disease-modifying therapy for obesity-associated steatotic liver disease, pending full efficacy/safety reporting.

Kaplan LM, Startseva E, le Roux CW et al. · Nature medicine · (2026) · View on PubMed ↗

REIMAGINE 1 was a phase 3a randomized, double-blind, placebo-controlled trial in adults with type 2 diabetes inadequately controlled on diet and exercise, testing once-weekly cagrilintide-semaglutide (CagriSema) versus placebo. CagriSema produced clinically meaningful improvements in glycaemic control and weight-related outcomes with an acceptable safety profile compared with placebo. This supports CagriSema as a next-generation once-weekly dual amylin/GLP-1 receptor therapy for type 2 diabetes requiring additional metabolic control.

Aroda VR, Buzzetti R, Dalskov SM et al. · The lancet. Diabetes & endocrinology · (2026) · View on PubMed ↗

REIMAGINE 2 was a phase 3 randomized, double-blind, controlled trial in people with type 2 diabetes and overweight/obesity comparing once-weekly cagrilintide-semaglutide (CagriSema) against semaglutide alone or cagrilintide alone. The fixed-dose combination demonstrated superior efficacy for glycaemic control relative to monotherapies while also leveraging complementary effects on body weight. These data strengthen the rationale for dual amylin–GLP-1 receptor agonism as an intensified treatment strategy in type 2 diabetes with excess adiposity.

Buse JB, Bajaj HS, Dalskov SM et al. · The lancet. Diabetes & endocrinology · (2026) · View on PubMed ↗

Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial.

This randomized, double-blind phase 3 trial studied adding the oral nonpeptide GLP-1 receptor agonist orforglipron to titrated insulin glargine in adults with type 2 diabetes with inadequate glycemic control across 72 US, Brazil, China, Japan, and Romania sites. Orforglipron added to insulin glargine improved glycemic outcomes versus insulin glargine alone while being evaluated for safety over 40 weeks (intervention details were truncated in the abstract). If effective and safe, this strategy could expand combination therapy options for adults with type 2 diabetes inadequately controlled on insulin glargine.

Giorgino F, D’Souza S, Ludwig L et al. · JAMA · (2026) · View on PubMed ↗

Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial.

This double-blind, placebo-controlled phase 3 randomized clinical trial studied once-weekly 9-mg mazdutide, a glucagon and GLP-1 receptor dual agonist, for weight reduction in Chinese adults with obesity (BMI ≥30), with and without type 2 diabetes. Mazdutide produced greater weight reduction than placebo over the trial period while assessing safety (primary efficacy/safety results were truncated in the abstract). If confirmed, mazdutide could provide an effective dual-agonist pharmacotherapy option for obesity management in Chinese populations.

Gao L, Jiang H, Cai H et al. · JAMA · (2026) · 1 citations · View on PubMed ↗

Plasma Aryl Hydrocarbon Receptor Agonist Activity Is Associated With Inflammation and Metabolic Dysregulation in Obesity: A Cross-Sectional Study.

This cross-sectional study measured plasma aryl hydrocarbon receptor (AhR) agonist activity in 80 non-diabetic participants across normal/healthy weight, overweight, and obese groups and related it to inflammation and metabolic dysregulation. Higher plasma AhR agonist activity was associated with inflammatory and metabolic abnormalities in obesity (specific effect estimates were truncated in the abstract). These findings suggest that circulating AhR agonist activity may be a mechanistic biomarker linking environmental/ligand signaling to obesity-related inflammation.

Bahman F, Kochumon S, Al Madhoun A et al. · Diabetes/metabolism research and reviews · (2026) · View on PubMed ↗ · Free PDF ↗

Time-restricted eating versus dietetic guidance on glycaemic outcomes in adults at risk of type 2 diabetes: a non-inferiority randomised clinical trial.

This multicenter, parallel-group randomized non-inferiority clinical trial compared time-restricted eating (TRE; 9-hour self-selected eating window) versus individualized dietetic guidance (IDG) in adults at risk of type 2 diabetes to assess change in HbA1c at 4 months. TRE was evaluated for non-inferiority to IDG on glycaemic outcomes in this at-risk population. If non-inferior, TRE could provide a simpler dietary strategy to reduce HbA1c in people with elevated risk for type 2 diabetes.

Parr EB, Charrouf R, Hutchison AT et al. · Diabetologia · (2026) · View on PubMed ↗ · Free PDF ↗

A subphenotype of obesity with reduced enteroendocrine GLP-1 synthesis and enhanced tirzepatide response.

This study evaluated mechanisms and treatment response in 483 adults with obesity by measuring solid meal gastric emptying (SGE) via scintigraphy, postprandial appetite, plasma enteroendocrine hormones, and mucosal gene expression, and then assessing response to tirzepatide across obesity subphenotypes. It identified a subphenotype characterized by reduced enteroendocrine GLP-1 synthesis and enhanced tirzepatide response. This is clinically significant because it suggests a biomarker-linked way to predict which patients with obesity will benefit more from tirzepatide.

Ticho AL, McRae AN, Cifuentes L et al. · Gastroenterology · (2026) · View on PubMed ↗

This double-blind, randomized, placebo-controlled phase 3 trial tested retatrutide, a GIP/GLP-1/glucagon receptor agonist, as monotherapy in adults with type 2 diabetes inadequately controlled by diet and exercise (HbA1c 7.0–9.5%) across 48 sites in the USA, Mexico, and India. It evaluated retatrutide’s efficacy and safety over 40 weeks compared with placebo in this defined population. The trial informs clinical use of a triple-incretin/glucagon strategy for improving glycemic control in type 2 diabetes with inadequate response to lifestyle alone.

Bajaj HS, Welch M, Shah P et al. · Lancet (London, England) · (2026) · 1 citations · View on PubMed ↗

Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Events in Adults With Obesity and Autoimmune Disease: A Target Trial Emulation.

This target trial emulation used 2014–2024 OneFlorida+ electronic health record data to evaluate associations between GLP-1 receptor agonist (GLP-1RA) use and major adverse cardiovascular and thromboembolic events in adults with obesity and autoimmune disease (AID). GLP-1RA exposure was analyzed as a comparative risk factor for cardiovascular/thromboembolic outcomes in this comorbid population. The study is significant because it provides real-world, quasi-experimental evidence to guide cardiovascular risk management when treating obesity in patients with AIDs.

Dai H, Lee YA, Natalie A et al. · Journal of the American Heart Association · (2026) · View on PubMed ↗ · Free PDF ↗

Interplay Between the Ketogenic Diet and the Gut Microbiome in Glioblastoma: A Comprehensive Review of Mechanisms and Clinical Implications.

This comprehensive review examined how the ketogenic diet (KD) interacts with the gut microbiome in glioblastoma (GBM), focusing on mechanistic pathways and clinical implications. The authors conclude that KD may exploit GBM metabolic vulnerabilities (reduced glucose dependence and limited ketone utilization), but clinical results are inconsistent due to small trials, adherence issues, and heterogeneous study designs. Scientifically, the review frames gut microbiome modulation as a key variable that could explain variability and inform future GBM trials combining KD with microbiome-aware strategies.

Mirzai M, Eslami M, Azizi AH et al. · Nutrition and cancer · (2026) · View on PubMed ↗

Genetic mechanisms and molecular stratification in rare GI disorders

PRDM9 Deficiency Drives Mosaic Promoter Deletions in Sporadic Hirschsprung Disease and Supports Blood-based Molecular Stratification.

This study investigated non-canonical genetic mechanisms in sporadic Hirschsprung disease (HSCR) by profiling RNA-seq from paired aganglionic and ganglionic colon biopsies in 103 patients and using blood-based whole-genome sequencing in a subset, with functional testing of PRDM9 in zebrafish, mice, and PRDM9-knockout hiPSC-derived enteric neural cells. It found that PRDM9 deficiency drives mosaic promoter deletions in sporadic HSCR and supports blood-accessible molecular stratification. The significance is that PRDM9-related mosaic genomic alterations may provide both mechanistic insight and a route to less invasive molecular diagnosis/stratification for HSCR.

Zhu Y, Zuo X, Song K et al. · Gastroenterology · (2026) · View on PubMed ↗

Novel variants in YTHDC2 cause non-obstructive azoospermia by disrupting the mitotic-to-meiotic transition in humans and mice.

This genetic and mechanistic study investigated biallelic variants in the YTHDC2 gene in humans with non-obstructive azoospermia (NOA) or severe oligozoospermia and in corresponding mouse models. The authors found that YTHDC2 missense variants disrupt the mitotic-to-meiotic transition, causing meiotic arrest and leading to NOA/severe oligozoospermia. These findings establish YTHDC2 as a human infertility gene and clarify a specific meiotic failure mechanism that could inform diagnosis and future fertility interventions.

Zhi A, Li M, Zubair M et al. · Human reproduction (Oxford, England) · (2026) · View on PubMed ↗

Mechanisms and evidence for manual/physical therapies

Manual Therapy Treatment Mechanisms are Complex: Challenges and a Call to Action.

This commentary studied how to conceptualize and measure treatment mechanisms for force-based manual therapies across preclinical and clinical contexts. It found that mechanism measurement is highly complex because local/regional interactions with unmeasured variables, time- and clinician-dependent effects, and inter-individual variability likely confound causal inference. The significance is a call to action for more rigorous, mechanistically informed research designs to improve manual therapy evidence.

Cook CE, Keter D, Napadow V et al. · Complementary therapies in medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Using prospective CARE Japan Study data (Jan 2022–Jan 2023), this study assessed how long COVID affects health-related quality of life (HRQoL) among Japanese adults, using SF-12 and modeling with adjusted beta regression plus latent class analysis (LCA). Long COVID status was analyzed as the primary independent variable to identify determinants of HRQoL and to characterize HRQoL subgroups. The findings are clinically significant because they quantify the HRQoL burden of long COVID in Japan and can inform targeted rehabilitation and support strategies.

Sultana S, Asai Y, Ishioka H et al. · Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · (2026) · View on PubMed ↗ · Free PDF ↗

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study.

This prospective cohort study evaluated hyperbaric oxygen therapy (HBOT) in 30 patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and assessed clinical outcomes and functional brain changes. After 40 HBOT sessions, HBOT improved clinical symptoms and functional capacity and was associated with modulation of thalamic connectivity. These findings support HBOT as a feasible intervention with measurable neurofunctional effects in ME/CFS, warranting further controlled trials.

Kim L, Cammà G, Peters CK et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Aging biology via iron, senescence, and ferroptosis

Fenofibrate attenuates hyperhomocysteinemia-potentiated thrombosis by restoring platelet fatty acid β-oxidation.

This Redox Biology study examined how hyperhomocysteinemia (HHcy) potentiates thrombosis by impairing platelet fatty acid β-oxidation (FAO), using integrated proteomic and lipidomic approaches. Homocysteine disrupted platelet lipid homeostasis by reducing FAO capacity, linking peroxisome–mitochondria metabolic coordination to platelet activation. Restoring platelet FAO may therefore be a mechanistic therapeutic direction to mitigate HHcy-associated thrombotic risk.

Han L, Du X, Yan Y et al. · Redox biology · (2026) · View on PubMed ↗

MCCC2 stabilizes LTBP1 via suppressing SMURF1-dependent ubiquitination to drive bone metastasis in prostate cancer.

This study examined how methylcrotonyl-CoA carboxylase subunit 2 (MCCC2) regulates LTBP1 stability and ubiquitination machinery (including SMURF1) to drive bone metastasis in prostate cancer cells and in vivo models. MCCC2 directly interacts with LTBP1 and promotes prostate cancer migration, invasion, and bone metastasis by suppressing SMURF1-dependent ubiquitination of LTBP1, stabilizing LTBP1. These findings identify the MCCC2–LTBP1 axis as a mechanistic driver and potential therapeutic target for preventing or treating prostate cancer bone metastasis.

Yang M, Chen Y, Lai S et al. · Oncogene · (2026) · View on PubMed ↗

Proteomic clocks combined with deep learning phenotypes track eye aging and diseases.

This study used high-throughput proteomics combined with deep learning (DL) phenotyping to model and validate proteomic aging and its association with age-related eye diseases across three large transethnic cohorts totaling over 55,000 participants. Proteomic aging signatures learned by machine learning closely tracked DL-derived eye aging phenotypes and revealed premature proteomic aging in major age-related eye diseases such as cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma. The work supports proteomic clocks as scalable, cross-cohort biomarkers for tracking eye aging and identifying individuals with early molecular risk for age-related eye disease.

Yang S, Xin Z, Li H et al. · NPJ digital medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Ameliorating calcium homeostasis improves longevity and healthspan in progeroid and naturally aged mice.

This study examined how improving calcium (Ca2+) homeostasis affects longevity and healthspan in Hutchinson-Gilford progeria syndrome (HGPS) and naturally aged mice, linking Ca2+ dysregulation to downstream senescence pathways. Disrupted Ca2+ homeostasis caused cytoplasmic accumulation of S100A6, which recruited CacyBP to promote ubiquitination and degradation of PARP1, leading to DNA damage, cytoplasmic chromatin fragments, activation of the cGAS–STING–NF-κB pathway, and SASP factor secretion; the tetracyclic antidepressant mianserin (MIA) attenuated senescence in HGPS patient-derived cells and naturally aging humans. These results support Ca2+ homeostasis as a modifiable upstream driver of progeroid and age-associated inflammation and suggest MIA or related strategies as potential interventions to improve healthspan.

Xiang W, Hu Q, Sun P et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Ferro-Aging: A Novel Paradigm Linking Iron Overload, Lipid Peroxidation and Cellular Senescence.

This mechanistic study proposed the “ferro-aging” paradigm linking iron overload to lipid peroxidation and cellular senescence, integrating pathways involving oxidative stress, mitochondrial damage, inflammaging, ferroptosis, and senescence. It found that age-related iron overload can initiate iron-catalyzed reactive oxygen species production and lipid peroxidation, culminating in cellular senescence and ferroptosis that exacerbate aging processes. The significance is that targeting iron-driven lipid peroxidation may represent a therapeutic strategy to modulate senescence/ferroptosis in age-related disease.

Gao S, Qi L, Bai W et al. · Free radical biology & medicine · (2026) · View on PubMed ↗

ATOX1 deficiency induces memory impairment via promoting cuproptosis in Alzheimer’s disease.

This study examined whether ATOX1 deficiency contributes to Alzheimer’s disease (AD) cognitive impairment by promoting cuproptosis, integrating analyses of human AD brain databases and tissue with mechanistic experiments (details truncated). It proposes that loss of the copper chaperone ATOX1 disrupts copper homeostasis, leading to intracellular copper overload and mitochondrial damage consistent with cuproptosis. The findings position ATOX1/cuproptosis as a potential therapeutic target for mitigating neurodegeneration in AD.

Yu H, Yi H, Jia D et al. · Journal of advanced research · (2026) · View on PubMed ↗ · Free PDF ↗

Effect of six weeks ubiquinol supplementation on mitochondrial respiratory function and exercise capacity in healthy males.

This randomized, double-blind, placebo-controlled trial studied whether 6-week supplementation with reduced coenzyme Q10 (ubiquinol, 300 mg/day) versus placebo affects skeletal muscle mitochondrial respiratory function and exercise capacity in 54 healthy, recreationally active males. The key finding is not fully visible in the truncated abstract, but the study was designed to test whether ubiquinol’s higher bioavailability translates into measurable improvements in mitochondrial function and endurance performance. Scientifically, the results would clarify whether reduced CoQ10 (ubiquinol) provides functional mitochondrial benefits beyond prior findings with oxidized ubiquinone.

Acton JP, Alsharif NS, Bond JW et al. · European journal of applied physiology · (2026) · View on PubMed ↗ · Free PDF ↗

Dissecting Immune Cell Ferroptosis via Single-Cell Multi-Omics Identifies RPL8 as a Potential Therapeutic Target for Depression.

This integrative study used two-sample Mendelian randomization (blood cis-eQTLs from eQTLGen/GTEx and depression from FinnGen), single-cell eQTL mapping in peripheral immune cells (OneK1K), and bioinformatics plus in silico docking to identify ferroptosis genes relevant to depression. It reports that MR implicated 42 ferroptosis genes and that replication across cohorts highlighted ribosomal protein RPL8 as a key protective factor. The significance is that RPL8 emerges as a candidate therapeutic target by linking immune-cell ferroptosis biology to depression risk.

Zhang G, He R, Du B et al. · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · (2026) · View on PubMed ↗

Overcoming redundancy in the Arabidopsis TREHALOSE-6-PHOSPHATE PHOSPHATASE family reveals connections to development and iron homeostasis.

This plant genetics study analyzed the Arabidopsis TREHALOSE-6-PHOSPHATE PHOSPHATASE (TPP) gene family by combining expression profiling, multiplex CRISPR-Cas9 editing, and metabolite profiling. While single/double mutants showed limited phenotypes, a CRISPR-Cas9 knockout of all 10 TPP genes increased shoot branching and caused earlier flowering, linking TPP redundancy to development and iron homeostasis (details truncated). The work clarifies how overlapping TPP functions regulate key developmental traits and nutrient-related physiology in Arabidopsis.

Skopelitis T, Swentowsky KW, Goldshmidt A et al. · The New phytologist · (2026) · View on PubMed ↗

Endoscopy and gastrointestinal procedural therapeutics

A peptide-first hemostatic strategy for oozing-type post-sphincterotomy bleeding during ERCP: a multicenter noninferiority randomized controlled trial (PROTECT-EST).

This multicenter, noninferiority randomized controlled trial studied adults undergoing ERCP with oozing-type immediate post-sphincterotomy bleeding, comparing a self-assembling peptide (SAP)-first hemostatic strategy versus conventional balloon tamponade. It found that the SAP-first approach was noninferior to balloon tamponade for controlling persistent oozing-type bleeding after endoscopic sphincterotomy. The clinical significance is that SAP could become a first-line, minimally disruptive hemostatic option during ERCP for this common complication.

Ogura T, Ikeura T, Takenaka M et al. · Gastrointestinal endoscopy · (2026) · View on PubMed ↗

Intraocular Pressure Changes Following Intraluminal Stent Removal from the Paul Glaucoma Implant: A Systematic Review and Meta-Analysis.

This systematic review and single-arm meta-analysis evaluated intraocular pressure (IOP) changes after intraluminal stent removal from the Paul glaucoma implant (PGI) and summarized long-term efficacy and safety. It synthesized available clinical evidence to characterize how IOP responds following this specific glaucoma drainage device management step. The results are intended to inform surgical decision-making for refractory glaucoma by clarifying expected IOP outcomes and durability after stent removal.

Lan CH, Pao SI, Tseng HL et al. · American journal of ophthalmology · (2026) · View on PubMed ↗

Clinical outcomes of endoscopic resection for remnant gastric cancer: a multicenter prospective cohort study.

This multicenter prospective cohort study evaluated clinical outcomes of endoscopic resection (ER) for remnant gastric cancer (RGC) in Japan, comparing 355 patients with 369 RGCs to 8460 patients with 9394 primary early gastric cancers (EGC) across 41 centers. The study calculated 5-year overall survival (OS) and disease-specific survival (DSS) and used Cox regression to estimate hazard ratios for all-cause mortality. The results are important for determining whether ER is a valid, less invasive treatment option for early-stage RGC as its incidence increases.

Toya Y, Matsumoto T, Suzuki H et al. · Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · (2026) · View on PubMed ↗

Intraoperative measurement of breast-conserving surgery margins: surgical application.

This review evaluated intraoperative approaches for measuring breast-conserving surgery (BCS) margins to reduce the rate of re-excision when malignant cells are present at the inked margin. It compares traditional margin assessment methods with emerging technologies such as new imaging devices and molecular probes for surgical navigation (specific techniques and comparative performance truncated). The review’s significance is to guide surgical and diagnostic selection toward more accurate, real-time margin evaluation to improve BCS outcomes.

Chen WL, Liu WL, Guo CP et al. · Breast cancer research : BCR · (2026) · View on PubMed ↗ · Free PDF ↗

The effects of mechanical ventilation during v-a ecmo support: a systematic review.

This systematic review assessed how mechanical ventilation settings and adjunctive respiratory interventions affect hemodynamics, cardiac recovery, and clinical outcomes in adults supported with veno-arterial (V-A) ECMO. The review synthesized evidence up to June 6, 2025, focusing on ventilation strategies during V-A ECMO. The findings are intended to guide safer, more physiologically informed ventilator management during ECMO to support cardiac recovery.

Protti I, Di Tomasso N, Meani P et al. · Critical care (London, England) · (2026) · View on PubMed ↗ · Free PDF ↗

Genetic risk and biomarkers in liver disease (MASLD/PBC/MASH)

PNPLA3 polymorphisms and risk of hepatic and extrahepatic outcomes in MASLD: a meta-analysis of observational studies.

This meta-analysis studied the prognostic impact of PNPLA3 polymorphisms, particularly rs738409 C>G (PNPLA3 I148M), on hepatic and extrahepatic outcomes in metabolic dysfunction–associated steatotic liver disease (MASLD). It found that PNPLA3 polymorphisms are associated with altered risk of developing long-term clinical outcomes in MASLD. The significance is that PNPLA3 genotyping may help refine risk prediction for MASLD patients beyond liver outcomes.

Celsa C, Pennisi G, Tulone A et al. · JHEP reports : innovation in hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Steatotic Liver Disease at Primary Biliary Cholangitis Diagnosis: Association With Ursodeoxycholic Acid Response and Outcomes.

This retrospective multicenter cohort study used the Spanish ColHai registry to evaluate how steatotic liver disease (SLD), including MASLD criteria, affects ursodeoxycholic acid (UDCA) response and outcomes in patients with primary biliary cholangitis (PBC). Among 469 PBC patients with data, 33.7% had SLD and 78.5% of those met MASLD diagnostic criteria, and the study assessed associations with UDCA treatment response and prognosis (results truncated). Clinically, recognizing SLD/MASLD at PBC diagnosis may refine prognosis and expectations for UDCA effectiveness.

Del Barrio M, Sala M, Gómez J et al. · Liver international : official journal of the International Association for the Study of the Liver · (2026) · View on PubMed ↗ · Free PDF ↗

Tumor microenvironment and immune cell targeting in cancer

Septin multimer autoantibodies in severe motor neuropathy mimicking lower motor neuron disease.

This study investigated a novel pattern of septin multimer autoantibodies in severe motor neuropathy that can mimic lower motor neuron disease (LMND), using murine teased sciatic nerve fibers to identify target antigens. Antigens were identified by immunoprecipitation followed by mass spectrometry and validated with cell-based assays, neutralization assays, and knockout models, then assessed in a retrospective neuropathy cohort. Clinically, detecting these septin multimer autoantibodies could help distinguish autoimmune severe motor neuropathy from fatal LMND and guide immunotherapy decisions.

Arlt FA, Miske R, Appeltshauser L et al. · Brain : a journal of neurology · (2026) · View on PubMed ↗

Herpesvirus Retinitis by Immune Status: Clinical Phenotypes and Predictors of Retinal Detachment and Severe Visual Impairment.

This retrospective longitudinal cohort study analyzed 120 patients (144 eyes) with acute retinal necrosis (ARN) or cytomegalovirus retinitis (CMVR) among 1,175 screened for suspected herpesvirus retinitis, focusing on how immune status relates to retinal detachment (RD) phenotypes and severe visual impairment. Across diagnoses defined by SUN criteria regardless of PCR status, specific RD patterns and clinical factors were associated with higher risk of RD and severe visual outcomes. These predictors can improve risk stratification and treatment planning for herpesvirus retinitis, potentially reducing vision loss.

Zou Y, Yang M, Zhang J et al. · Ophthalmology. Retina · (2026) · View on PubMed ↗

Cancer-associated and non-neoplastic fibrosis: Comparative mechanisms and emerging antifibrotic strategies.

This 2026 review compared mechanisms of cancer-associated fibrosis with non-neoplastic fibrosis, using idiopathic pulmonary fibrosis as a reference model and focusing on fibrotic tumors including pancreatic, hepatocellular, colorectal, and triple-negative breast cancers. It highlighted conserved pathways driving fibroblast activation and extracellular matrix remodeling, alongside tumor-specific roles in immune evasion, drug delivery failure, and therapy resistance. The review synthesizes emerging antifibrotic strategies to inform translational approaches targeting fibrosis across both disease and cancer contexts.

Riccò B, Grisendi G, Monaco AL et al. · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · (2026) · View on PubMed ↗

Integrative single-cell and spatial transcriptomics analysis reveals a baicalein-responsive 10-gene signature for non-small cell lung cancer.

This integrative single-cell and spatial transcriptomics study analyzed non-small cell lung cancer (NSCLC) to define baicalein-responsive genes and a 10-gene signature, combining network pharmacology, single-cell RNA-seq, bulk transcriptomics, spatial transcriptomics, machine learning, and in vitro validation. Baicalein-responsive targets were enriched in a 32-gene core set, and consensus clustering identified three molecular subtypes associated with the derived 10-gene signature. The resulting signature provides a cell-type- and spatially informed biomarker framework for predicting baicalein responsiveness and guiding NSCLC therapeutic research.

Wu D, Liu C, Zhan L et al. · Translational oncology · (2026) · View on PubMed ↗

Structure-Informed Design of Distinct Parallel G-Quadruplex Stabilizers for KRAS-Driven Cancer Therapy.

This study used structure-informed screening and rational medicinal chemistry to develop distinct parallel G-quadruplex (G4) stabilizers targeting KRAS proximal promoter G4s (KRAS-G4) for KRAS-driven cancer therapy. Dehydroevodiamine (DEE) was identified as a KRAS-G4 stabilizer, and structural analysis enabled synthesis of 15 DEE analogues with compound 7i emerging as the lead candidate. By improving potency and structural diversity of KRAS-G4 ligands, this work advances a potential therapeutic approach that directly targets oncogene promoter G4 DNA.

Zhang L, Han K, Wang X et al. · Angewandte Chemie (International ed. in English) · (2026) · View on PubMed ↗

Comprehensive multi-omics pan-cancer analysis revealed that ANTXR1 is a potential biomarker for diagnosis and immunotherapy.

This integrative multi-omics pan-cancer analysis investigated anthrax toxin receptor 1 (ANTXR1/TEM8) as a diagnostic and immunotherapy biomarker across cancers using TCGA, GTEx, and public datasets, with single-cell and spatial transcriptomics to map expression patterns. ANTXR1 showed aberrant expression across multiple tumor types and was linked to prognostic/diagnostic value and immune associations, with functional validation performed in gastric cancer using in vitro and in vivo models (details truncated). If validated clinically, ANTXR1 could help stratify patients for immunotherapy and improve biomarker-driven cancer diagnosis.

Qiu Y, Yu Z, Lai W et al. · Biology direct · (2026) · View on PubMed ↗ · Free PDF ↗

RAD21 regulation of the enhancer-promoter chromatin loop of RAD51 promotes PARPi resistance in ovarian cancer.

This study examined how RAD21 regulates the enhancer–promoter chromatin loop of RAD51 to drive PARP inhibitor resistance in ovarian cancer. Using Hi-C to map chromatin organization under olaparib exposure and generating an olaparib-resistant ovarian cancer cell line, the authors found that RAD21-mediated RAD51 looping promotes PARPi resistance (full mechanistic outcomes were truncated). Targeting the RAD21–RAD51 chromatin-loop axis could help overcome resistance to PARP inhibitors such as olaparib in ovarian cancer.

Gou R, Chang X, Cheng H et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

NOTCH3 regulates myofibroblastic CAF differentiation via the P62-ROS signaling axis to promote bladder cancer progression.

This work investigated how NOTCH3 regulates myofibroblastic cancer-associated fibroblast (CAF) differentiation via a P62–ROS signaling axis to promote bladder cancer progression. By integrating patient-derived CAFs with bulk and single-cell transcriptomics, spatial transcriptomics, immunohistochemistry, and multiplex immunofluorescence, and validating with PCR, immunoblotting, and immunofluorescence, the study defined a CAF-driven mechanism centered on NOTCH3 signaling (key results truncated). Elucidating this pathway may identify therapeutic targets to disrupt pro-tumor CAF differentiation in bladder cancer.

Hu D, Shen C, Liu C et al. · Journal of experimental & clinical cancer research : CR · (2026) · View on PubMed ↗ · Free PDF ↗

This multi-omics Mendelian randomization study identified macrophage polarization (MP)-related genes associated with esophageal cancer risk by integrating mQTL, eQTL, and pQTL data with esophageal cancer GWAS. Using UK Biobank discovery and FinnGen R10 validation, SMR and colocalization analyses tested whether gene methylation/expression/protein levels causally relate to esophageal cancer risk (specific gene hits were truncated). The approach prioritizes MP-related genetic targets that could inform risk prediction and mechanistic research in esophageal cancer.

Shi M, Zhou R, Yu B et al. · Clinical epigenetics · (2026) · View on PubMed ↗ · Free PDF ↗

Association of baseline immune cell composition with CAR-T cell expansion and survival in Relapsed/Refractory large B-Cell lymphoma.

This exploratory retrospective study analyzed 33 patients with relapsed/refractory large B-cell lymphoma (R/R LBCL) treated with CD19/CD22 bispecific CAR-T therapy (CAR2219) to relate baseline peripheral blood immune subset composition to CAR-T expansion kinetics and survival. Baseline immune cell composition was associated with differences in CAR-T expansion and persistence, which in turn correlated with clinical outcomes. These findings suggest that pretreatment immune profiling could help predict CAR-T performance and guide more personalized CAR-T strategies in R/R LBCL.

Liu XD, Wang HN, Zeng LJ et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

SERPINE2-mediated activation of JAK2/STAT3 facilitates NRF2 nuclear translocation and GCLC transcription to confer ferroptosis resistance and lenvatinib resistance in hepatocellular carcinoma.

This study investigated how SERPINE2 promotes lenvatinib resistance in hepatocellular carcinoma (HCC) by activating the JAK2/STAT3 pathway to drive NRF2 nuclear translocation and GCLC transcription, thereby suppressing ferroptosis. In hypoxic and acquired lenvatinib-resistant HCC models, SERPINE2-mediated JAK2/STAT3–NRF2 signaling increased GCLC expression and conferred ferroptosis and lenvatinib resistance, supported by in vivo xenograft and orthotopic mouse experiments. Mechanistically targeting the SERPINE2–JAK2/STAT3–NRF2–GCLC axis may restore ferroptosis sensitivity and overcome lenvatinib resistance in advanced HCC.

Liu K, Huang S, Xu Y et al. · Journal of experimental & clinical cancer research : CR · (2026) · View on PubMed ↗ · Free PDF ↗

Decoding TNF receptor superfamily control of CD4+Foxp3+ Regulatory T cell-mediated tolerance: implications for the treatment of graft‑versus‑host disease.

This review article examined how members of the TNF receptor superfamily (TNFRSF) regulate CD4+Foxp3+ regulatory T cell (Treg) biology and tolerance mechanisms relevant to graft-versus-host disease (GvHD) treatment. It highlights TNFRSF-dependent control of Treg stability and function as a rationale for precision Treg-directed therapies rather than broad immunosuppression. The synthesis provides mechanistic targets within TNFRSF pathways that could enable more stable, functional Tregs to preserve graft-versus-leukemia effects while reducing GvHD.

Chou CK, Wang X, Yu R et al. · Cell communication and signaling : CCS · (2026) · View on PubMed ↗ · Free PDF ↗

Anti-NRP1 peptide-engineered ROS/pH dual-responsive nanoparticles for Alpelisib delivery regulate Sema3A-NRP1/PI3K-AKT signaling to balance oxidative stress and inhibit angiogenesis in endometriosis.

This preclinical study developed ROS/pH dual-responsive nanoparticles (Alp@TAT-AT7-NPs) engineered with an anti-NRP1 peptide to deliver the PI3K inhibitor alpelisib for endometriosis treatment. The nanoparticles selectively entered NRP1-overexpressing endothelial cells, inhibited NRP1 and downstream PI3K/AKT signaling, reduced reactive oxygen species (ROS), and suppressed angiogenesis in vitro and in an endometriosis rat model. Targeting the Sema3A–NRP1/PI3K–AKT axis with responsive alpelisib nanocarriers may rebalance oxidative stress and angiogenesis to limit endometriosis progression.

Zhang J, Zhang H, Liu W et al. · Journal of nanobiotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

LncRNA 606938-TFAM axis drives oxidative stress and activates cGAS-STING pathway-mediated antitumor immunity to restrain colorectal cancer progression.

This study investigated how the lncRNA 606938–TFAM axis regulates oxidative stress and activates the cGAS–STING pathway to drive antitumor immunity and restrain colorectal cancer progression. The authors linked lncRNA 606938/TFAM-mediated control of reactive oxygen species (ROS) to enhanced innate immune signaling via cGAS–STING, promoting a more immunogenic tumor state. Targeting the 606938–TFAM–ROS–cGAS–STING axis could represent a strategy to convert “cold” colorectal tumors into responsive ones for immunotherapy.

Du J, Guo Z, Lu Q et al. · Oncogene · (2026) · View on PubMed ↗

Impact of fludarabine dosage on outcomes in large B-cell lymphoma patients treated with CAR T-cell therapy: a retrospective study of the CTIWP of the EBMT.

This retrospective EBMT registry study evaluated whether lymphodepleting conditioning fludarabine dose affects outcomes in large B-cell lymphoma patients receiving CD19 CAR T-cell therapy with either tisagenlecleucel (tisa-cel) or axicabtagene ciloleucel (axi-cel). In the tisa-cel cohort, higher fludarabine dosing (82.6–120 mg/m2) was associated with worse overall survival, whereas axi-cel patients received more consistent standard dosing. Clinically, the results suggest that fludarabine dose optimization in lymphodepletion may improve survival for tisa-cel recipients.

Dachy G, Mooyaart JE, Gabellier L et al. · Bone marrow transplantation · (2026) · View on PubMed ↗

Discovery of BEND4 as a novel single-gene prognostic marker and therapeutic target for adverse AML.

This study used transcriptome analyses of primary acute myeloid leukemia (AML) cohorts (n=1338) and independent validation (n=350) to identify BEN domain-containing protein 4 (BEND4) as a prognostic marker and potential therapeutic target in adverse-risk AML. BEND4 was found to be significantly overexpressed in adverse cytogenetic risk and associated with relapse and refractory disease features. The identification of BEND4 as a single-gene prognostic biomarker and target could improve risk stratification and open new avenues for targeted therapy in AML patients lacking canonical mutations.

Banerjee A, Mishra SV, Dsouza CA et al. · NPJ precision oncology · (2026) · View on PubMed ↗ · Free PDF ↗

IQGAP3 bridges matrix stiffness with glioma stem cell maintenance and radioresistance by stabilizing SOX2.

This study investigated how tumor microenvironment matrix stiffness influences glioblastoma stem cell (GSC) maintenance and radioresistance, focusing on IQGAP3 and its stabilization of the stemness factor SOX2. Increased matrix stiffness induced IQGAP3 via YAP1/TEAD signaling in GSCs, and IQGAP3 promoted GSC self-renewal and survival after radiation by binding and stabilizing SOX2; inhibiting IQGAP3 reduced SOX2 levels and increased radiosensitivity in vitro and in vivo. These findings position IQGAP3 as a mechanistic link between mechanical cues and therapy resistance and suggest a potential target to radiosensitize glioblastoma.

Zhang P, Wu W, Huang T et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Multi-omic profiling identifies TREM2+ lipid-laden macrophages as inflammatory drivers and therapeutic targets of colorectal cancer liver metastasis.

This study used integrated multi-omic profiling—including CyTOF, single-cell and spatial transcriptomics, bulk RNA-seq, and lipidomics—to characterize tumor-associated macrophage subsets in colorectal cancer liver metastasis (CRLM). It identified a distinct TREM2+ lipid-laden, immunosuppressive macrophage population enriched in CRLM that expresses lipid metabolism genes such as APOE, LIPA, and GPNMB and localizes preferentially to invasive margins. The significance is that TREM2+ lipid-laden macrophages may be actionable therapeutic targets to disrupt metastatic immune suppression in CRLM.

Wang PX, Zhong YC, Zheng WJ et al. · Cancer letters · (2026) · View on PubMed ↗

Targeting C/EBPβ/SCD1/C16:1 loop-driven macrophage M2 polarization by Bruceine D improves anti-PD-1 immunotherapy in colorectal cancer.

This study tested whether Bruceine D (BD), a natural compound, can reprogram macrophage immunometabolism by targeting the C/EBPβ/SCD1/C16:1 loop to reduce M2-like tumor-associated macrophages and thereby improve anti-PD-1 therapy in colorectal cancer using MC38 and CT26 syngeneic mouse models plus THP-1-derived macrophages, bone marrow-derived macrophages (BMDMs), and human monocytic cells. BD inhibited M2-like macrophage polarization and suppressed tumor progression while enhancing anti-programmed cell death protein 1 (anti-PD-1) efficacy without significant systemic toxicity. These findings support a macrophage-targeted metabolic mechanism (C/EBPβ/SCD1/C16:1) as a potential combination strategy to overcome immune checkpoint resistance in CRC.

Zhao L, Huang W, Li C et al. · Cancer letters · (2026) · View on PubMed ↗

Targeting BRD4 to reverse organ fibrosis: Epigenetic regulation, cellular plasticity, and therapeutic potential.

This review synthesized evidence on how the BET-family epigenetic reader BRD4 regulates fibrotic progression across organs by integrating upstream injury signals such as TGFβ, NF-κB, oxidative stress, and mechanotransduction. It concludes that BRD4 sustains transcription of pro-fibrotic/pro-inflammatory programs, promotes myofibroblast activation, and reinforces pathological cellular plasticity, contributing to extracellular matrix deposition, EMT/EndMT, and inflammatory amplification. The article highlights BRD4 as a therapeutic target for developing fibrosis-reversing epigenetic interventions.

Nisar A, Khan S, Li W et al. · Pharmacology & therapeutics · (2026) · View on PubMed ↗

Dysregulated transcription in core- and pol-specific CD8 T cells can be targeted by HDAC inhibition to improve T-cell function in chronic hepatitis B.

This study profiled core- and polymerase-specific CD8 T cells from untreated highly viremic HBeAg-negative chronic hepatitis B (CHB) patients and compared them with cells from patients achieving functional cure after nucleos(t)ide-analog treatment and from acute hepatitis B (rACU) using RNA-sequencing and measurements of histone acetylation and cytokine production. It found that dysregulated transcription programs in these CD8 T cells can be targeted by histone deacetylase (HDAC) inhibition to improve T-cell function. These results suggest HDAC-targeted epigenetic therapy as a potential strategy to restore HBV-specific CD8 T-cell activity and support CHB cure efforts.

Ceccatelli Berti C, Montali I, Doselli S et al. · Journal of hepatology · (2026) · View on PubMed ↗

PAD4-mediated citrullination of IGF2BP2 stabilizes MCM mRNAs to drive intrahepatic cholangiocarcinoma progression.

This study investigated how peptidyl arginine deiminase 4 (PAD4)-mediated citrullination affects intrahepatic cholangiocarcinoma (ICC) progression by focusing on citrullination of the RNA-binding protein IGF2BP2 and its downstream stabilization of MCM mRNAs, using hydrodynamic tail vein injection (HTVI) and subcutaneous xenograft models. It reports that PAD4 promotes ICC growth by citrullinating IGF2BP2, which stabilizes MCM transcripts to drive proliferation. The work identifies the PAD4–IGF2BP2–MCM axis as a mechanistic and potentially druggable pathway for ICC therapy.

Tian G, Zou L, Zhang M et al. · Journal of advanced research · (2026) · View on PubMed ↗ · Free PDF ↗

Multimodal Artificial Intelligence Prediction of Abiraterone Efficacy in Two STAMPEDE Phase 3 Trials of Non-Metastatic Very High-Risk Prostate Cancer.

This study used a previously validated multimodal artificial intelligence (MMAI) digital pathology model to predict abiraterone benefit in non-metastatic clinically very high-risk prostate cancer patients enrolled in two STAMPEDE phase 3 trials. It generated MMAI scores for trial participants and assessed whether the model could stratify who would derive outcome benefit from adding abiraterone to long-term androgen deprivation therapy plus radiotherapy. If validated, this approach could enable biomarker-guided selection to reduce unnecessary abiraterone exposure and toxicity in this high-risk population.

Parker CTA, Huang HC, Grist E et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Transcription factors as drivers of 3D enhancer-promoter interactions.

This article reviewed how transcription factors drive specific 3D enhancer–promoter interactions beyond general mechanisms like cohesin/CTCF and RNA polymerase II. It emphasizes that tissue-specific transcription factor loss experiments and newer protein-degradation tools have helped clarify how enhancer–promoter pairing achieves cell-type and state specificity. The review highlights emerging experimental approaches for mapping the causal roles of transcription factors in 3D genome regulation.

Aboreden NG, Blobel GA · Current opinion in structural biology · (2026) · View on PubMed ↗

SLC22A3/OCT3 drives serotonin-mediated stemness in pancreatic cancer.

The study investigated how the transporter gene SLC22A3/OCT3 regulates serotonin-mediated stemness in pancreatic cancer, focusing on cancer stem cell (CSC) biology. SLC22A3/OCT3 was identified as a reactivated embryonic-associated signature that drives pancreatic cancer stemness programs, linking OCT3 activity to serotonin-dependent stemness mechanisms. These findings are significant because they nominate SLC22A3/OCT3 as a mechanistic regulator of CSC stemness and a potential therapeutic target to limit pancreatic cancer progression and resistance.

Krishna Kumar N, Varadharaj V, Gayen N et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

TRIM47 drives metabolic reprogramming and tumor progression in Nasopharyngeal Carcinoma via K48-linked ubiquitination and degradation of SDHB.

This study examined how TRIM47 contributes to metabolic reprogramming and tumor progression in nasopharyngeal carcinoma (NPC) by promoting K48-linked ubiquitination and degradation of SDHB. In integrated in vitro and in vivo experiments, TRIM47 was shown to be upregulated in NPC and to enhance proliferation, migration, EMT, and tumor growth through direct interaction with SDHB. The work is significant because it identifies a TRIM47–SDHB ubiquitination axis that may be exploited to disrupt NPC metabolism and progression therapeutically.

Yu J, Ding L, Yang Y et al. · Cellular and molecular life sciences : CMLS · (2026) · View on PubMed ↗ · Free PDF ↗

Single-cell immunoprofiling reveals a dysfunctional-like immune microenvironment and malignant phenotype in aging penile squamous cell carcinoma.

This study examined differences between non-old (n=2) and old (n=3) patients with penile squamous cell carcinoma (PSCC) using single-cell RNA sequencing and single-cell TCR-Seq, with UMAP clustering and trajectory analyses of tumor cells, T cells, and myeloid cells. It reports that aging PSCC shows a dysfunctional-like immune microenvironment together with a malignant phenotype, supported by additional validation using immunohistochemistry (DCN, KITLG, GPX4, EPCAM) and immunofluorescence (CD24, MIF). The clinical significance is that age-associated immune dysfunction in PSCC may help refine diagnosis and guide more precise treatment strategies for older patients.

Cao J, Du L, Qin Z et al. · Cell biology and toxicology · (2026) · View on PubMed ↗ · Free PDF ↗

This retrospective cohort study evaluated predictors of response and survival in [18F]FDG-positive metastatic castration-resistant prostate cancer (mCRPC) treated with [177Lu]Lu-PSMA-I&T, using baseline dual-tracer PET/CT with [68Ga]Ga-PSMA-11 and [18F]FDG. The key finding is that baseline characteristics, including dual-tracer PET parameters, were assessed for correlation with response and for prognostic association with progression-free survival (PFS) and overall survival (OS) in this FDG-positive population. The significance is that identifying PET-derived predictors could improve patient selection and outcome stratification for PSMA-ligand radionuclide therapy in advanced prostate cancer.

Santo G, di Santo G, Kronthaler A et al. · European journal of nuclear medicine and molecular imaging · (2026) · View on PubMed ↗ · Free PDF ↗

Machine learning models predict the immunotherapy response in tumors on the basis of DNA methylation.

This study developed machine learning models to predict tumor immunotherapy response using DNA methylation features, alongside immunotherapy-relevant genomic variables such as tumor mutational burden (TMB), neoantigen burden, and PD-L1. It screened variably methylated loci linked to immunotherapy response, summarized QTL features, and analyzed expression of immunotherapy-related methylation loci to train predictive models. The significance is that methylation-based models could improve biomarker-driven selection for immunotherapy by more reliably estimating response rates.

Gu Z, Jiang N, Deng E et al. · Epigenomics · (2026) · View on PubMed ↗

“Outstanding” ADC Candidates Emerge for SCLC, Other Cancers.

This Cancer Discovery report summarized early clinical data from phase I/II trials of antibody-drug conjugates (ADCs) in small cell lung cancer (SCLC) and other cancers. Reported early responses included CD56-targeting DXC006, DLL-3-targeting BL-M14D1, and B7-H3-targeting SYS6043 (with SYS6043 also active in ovarian and breast cancers), and phase II data suggested strong efficacy of HER2-targeting trastuzumab brengitecan in platinum-resistant ovarian cancer. These findings support rapid expansion of ADC options for SCLC and highlight multiple tumor-associated targets (CD56, DLL-3, B7-H3, HER2) with emerging clinical activity.

Cancer discovery · (2026) · View on PubMed ↗

Autoimmune nodopathy associated with contactin-2 antibodies manifesting as Guillain-Barré syndrome: a case report.

This case report described autoimmune nodopathy at the node of Ranvier associated with contactin-2 (CNTN2) antibodies presenting as Guillain-Barré syndrome. The authors reported clinical and electrophysiological features consistent with anti-CNTN2 autoimmune nodopathy, highlighting a previously unreported antibody–phenotype association. Recognizing anti-CNTN2 antibodies in GBS-like presentations may improve diagnostic accuracy and inform immunotherapy decisions.

Zeng X, Hu J, Li K et al. · Journal of medical case reports · (2026) · View on PubMed ↗ · Free PDF ↗

Microglial galectin-3 disrupts parvalbumin interneurons and hippocampal synchrony, driving cognitive deficits.

This study investigated sepsis-associated encephalopathy (SAE) mechanisms in an LPS-induced mouse model by focusing on microglial galectin-3 (Gal-3). LPS upregulated microglial Gal-3, which activated TLR2 signaling and promoted NLRP3/AIM2 inflammasome pathways, disrupting parvalbumin interneurons and hippocampal synchrony and driving cognitive deficits. These results identify Gal-3 as a mechanistic mediator and potential therapeutic target to prevent persistent cognitive impairment after sepsis.

Jia M, Shao H, Ma SQ et al. · Journal of neuroinflammation · (2026) · View on PubMed ↗ · Free PDF ↗

Obesity-driven cancer biology and tumor microenvironment

Obesity promotes Aggressiveness of Endometrial Cancer via Metabolic Reprogramming and Intercellular Crosstalk in the Tumor Microenvironment.

This study investigated how obesity promotes endometrial cancer aggressiveness by combining a uterine endometrium pten conditional knockout mouse model, analyses of patient clinical samples, and single-cell RNA sequencing from 10 endometrial tumor samples. It found that obesity drives metabolic reprogramming and intercellular crosstalk within the tumor microenvironment that is linked to more aggressive endometrial cancer behavior. The significance is that obesity-associated tumor microenvironment changes may reveal targets for improving prognosis and tailoring prevention or therapy in patients with obesity.

Chen Y, Fang Y, Zhao G et al. · Cancer letters · (2026) · View on PubMed ↗

Neurodevelopmental disorders and synaptic/circuit mechanisms

This study applied interpretable machine learning to fMRI data from multiple datasets (total n=390) to derive brain neuromarkers that predict mentalizing about the self and about other people across adult, clinical, and developmental samples. The resulting self-mentalizing and other-mentalizing classifiers used distinct brain signature weights and could predict both types of mentalizing. The work provides replicable, testable neuroimaging biomarkers that may help characterize and potentially stratify psychiatric and neurodevelopmental conditions involving impaired mentalizing.

Açıl D, Andrews-Hanna JR, López-Solà M et al. · Nature communications · (2026) · View on PubMed ↗

Psychological stress exacerbates vitiligo via dysregulated proteolysis of substance P and MRGPRX2-dependent mast cell activation.

This study investigated whether psychological stress worsens vitiligo through dysregulated proteolysis of substance P (SP) and mast cell activation dependent on MRGPRX2 (MRGPRB2 in mice). In human active vitiligo biopsies and in mice exposed to chronic restraint stress, the authors tested SP and its proteolytic fragments (SP1-9 and SP1-7) and used a Tyrp-2180-188 peptide-induced vitiligo model in wild-type and MrgprB2 knockout mice to assess the role of MRGPRX2-dependent mast cell activation. The work links stress-driven neuroimmune signaling (SP processing and MRGPRX2 mast cell activation) to vitiligo exacerbation, suggesting potential targets for stress-related disease progression.

Geng MM, Zhang SJ, Li XH et al. · Journal of dermatological science · (2026) · View on PubMed ↗

The study evaluated whether Huanglian Wendan decoction (HLWD) alleviates depression in an experimental model, assessing behavior (SPT, TST, OFT, SIT), neurogenesis, and gut-brain axis–related pathways including PPAR-α and allopregnanolone. HLWD improved depressive-like behaviors and was linked to modulation of PPAR-α–associated “allo” (allopregnanolone) signaling and related gut-brain mechanisms. These findings support HLWD as a potential gut-brain axis–targeting therapy for depression via PPAR-α/allopregnanolone pathways, warranting further mechanistic and translational work.

Sun Q, Zhao Y, Zhang J et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

Refined single-cell profiling captures a CCR5high CD4+ cytotoxic T-cell precursor in multiple sclerosis.

This work used refined single-cell profiling with spectral flow cytometry to characterize a CCR5high CD4+ cytotoxic T-cell precursor in blood and cerebrospinal fluid (CSF) from people with multiple sclerosis (MS). The authors identified a CCR5high CD4+ cytotoxic T-cell precursor with distinct brain-homing features compared with other CD4+ subsets, including Th17.1-related populations. The study advances MS immunobiology by pinpointing a specific CCR5high CD4+ cytotoxic precursor that may contribute to CNS pathology and could become a target for immune intervention.

van Puijfelik F, Rip J, van Hasselt Y et al. · EBioMedicine · (2026) · View on PubMed ↗ · Free PDF ↗

Promoting Research Excellence in Down Syndrome: Proceedings of the 5th International Conference of the Trisomy 21 Research Society.

This article describes the activities and goals of the Trisomy 21 Research Society (T21RS) and its 5th International Conference, focusing on research into Down syndrome (trisomy 21, T21) across disciplines and translational efforts. It highlights the society’s role in convening researchers, clinicians, self-advocates, families, and industry stakeholders to advance work relevant to DS-associated conditions, including early-onset Alzheimer’s disease risk. The significance is that it provides a coordinated, international platform intended to accelerate mechanistic and clinical research for DS and improve health and quality of life for affected individuals.

Di Domenico F, Perluigi M, Tramutola A et al. · Neuromolecular medicine · (2026) · View on PubMed ↗ · Free PDF ↗

This study investigated how CNTNAP2 (CASPR2) loss affects inhibitory interneurons and social behavior by quantifying calretinin-positive (CR+) and parvalbumin-positive (PV+) interneuron density in the caudoputamen and somatosensory cortex of Cntnap2 knockout (KO) versus wild-type (WT) mice. It found that Cntnap2 KO mice had lower CR+ interneuron density (and assessed relationships with altered social behavior). The significance is that it provides circuit-level evidence connecting CNTNAP2 dysfunction to altered excitatory–inhibitory balance, supporting mechanistic models of autism spectrum disorder.

Sáfár K, Szendi V, Hoppa P et al. · Autism research : official journal of the International Society for Autism Research · (2026) · View on PubMed ↗ · Free PDF ↗

Neural SMG7 deficiency induces autism-like behaviours via PKD1 upregulation.

This study examined the role of nonsense-mediated decay factor Suppressor with morphogenetic effect on genitalia 7 (Smg7) in autism-like behaviors using an Emx1-Cre-mediated conditional Smg7 knockout mouse model (Smg7cko). Smg7 deficiency induced autism-like behavioral phenotypes and was linked to upregulation of PKD1. These findings implicate the SMG7–PKD1 axis in neurodevelopmental dysfunction and suggest a mechanistic pathway that could be targeted to understand or treat autism spectrum disorder.

Pang Y, Hao A, Han H et al. · Brain : a journal of neurology · (2026) · View on PubMed ↗

Astrocyte-specific NRCAM deficiency promotes GABAergic synapse pruning to drive central sensitization in bone cancer pain.

This study examined whether astrocyte-specific deficiency of neuronal cell adhesion molecule (NRCAM) promotes GABAergic synapse pruning and central sensitization in a mouse model of bone cancer pain (BCP). Using intrafemoral inoculation of fibrosarcoma cells to induce BCP, the authors found that astrocytic NRCAM loss enhanced synaptic remodeling consistent with increased pruning of GABAergic synapses. This links astrocyte-mediated synaptic phagocytosis regulation to pain hypersensitivity and suggests NRCAM-related pathways as targets for BCP treatment.

Zhang Z, Hou Y, Mao Y et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Clinical decision support and acute endocrine management

Levetiracetam for Seizure Prophylaxis after Traumatic Brain Injury: A Severity-Stratified Cohort Study of 51,000 Patients.

This retrospective cohort study used the TriNetX Research Network to evaluate prophylactic levetiracetam in adults (≥18 years) after traumatic brain injury (TBI), stratified by Glasgow Coma Scale (GCS) severity (mild vs severe). It assessed the risk of early (<7 days) and late (<1 year) epilepsy while excluding patients with pre-existing epilepsy, seizures at injury, or prior levetiracetam exposure (outcomes truncated). The results aim to inform whether levetiracetam reduces post-TBI seizure risk and how effectiveness/adverse effects vary by TBI severity.

Thorman IB, Sacknovitz A, Li AG et al. · Annals of neurology · (2026) · View on PubMed ↗

Impact of Alert Systems on Glucocorticoid Administration for Adrenal Insufficiency in the Emergency Department.

This quasi-experimental study evaluated whether clinical decision support (CDS) improves the timing of intravenous hydrocortisone administration in patients with known adrenal insufficiency presenting to emergency departments (EDs). In 211 patients with adrenal insufficiency (66 patients with 187 ED encounters), the key finding was the effect of CDS on time-to-hydrocortisone administration compared with pre-intervention care. If CDS shortens treatment delays, it could reduce adrenal crisis risk by improving acute glucocorticoid management in the ED.

Greeviroj P, Anakepeerasak R, Thavaraputta S et al. · The Journal of clinical endocrinology and metabolism · (2026) · View on PubMed ↗

Epilepsy mechanisms and targeted ion-channel therapy

Kv7.2 loss-of-function causes early hyperexcitability and network remodelling.

This work studied developmental consequences of KCNQ2 loss-of-function (Kv7.2) variants using longitudinal, multimodal analyses in a human neuronal model generated from patients with KCNQ2-DEE and KCNQ2-SeLFNE. KCNQ2-LOF caused early Kv7-driven hyperexcitability with reduced M-current density at both single-cell and network levels, and acute treatment with the Kv7 opener retigabine rescued the hyperexcitability. These results support Kv7.2/M-current dysfunction as an early, drug-reversible mechanism in neonatal epilepsies and strengthen the rationale for early targeted Kv7 modulation.

Dirkx N, Kaji M, De Vriendt E et al. · Brain : a journal of neurology · (2026) · View on PubMed ↗

Infectious disease vaccines and host-pathogen mechanisms

Pharmacologic reprogramming of virus-tumor crosstalk enhances measles virus antitumor activity in BRAF mutant colorectal cancer models.

This preclinical study tested whether pharmacologic reprogramming of virus–tumor interactions using triptolide and its prodrug Minnelide enhances oncolytic measles virus (MV) antitumor activity in BRAF-mutant colorectal cancer models. Co-treatment with triptolide/Minnelide increased the efficacy of CD46-targeted (MV-GFP) and dual-targeted (MV-CD46-muPA) measles virus by modulating tumor stress and survival pathways that otherwise limit durable virotherapy responses. These results support combining oncolytic measles virus with triptolide-family drugs as a strategy to improve durability in BRAF-mutant CRC.

Chavez V, Montero M, Tran NHG et al. · Journal of experimental & clinical cancer research : CR · (2026) · View on PubMed ↗ · Free PDF ↗

The Legionella effector RidL binds the large fission GTPase Drp1 to promote mitochondrial fragmentation.

This mechanistic study identified the Legionella effector RidL as a mitochondrial-targeting factor that binds the large fission GTPase Drp1 to promote mitochondrial fragmentation during infection. RidL’s C-terminal domain directly bound Drp1, reduced Drp1 GTPase activity and oligomerization in vitro, and during infection localized to mitochondria while increasing Drp1 and the outer membrane protein Tom20 to impair mitochondrial dynamics. These findings reveal a new host-targeting mechanism for Legionella survival and suggest Drp1 regulation as a potential intervention point against intracellular infection.

Katic A, Vittori ET, Halter S et al. · EMBO reports · (2026) · View on PubMed ↗ · Free PDF ↗

Optimization of IS621 recombinase/bridge RNA-directed recombination for precise insertion of large DNA fragments in human cells.

This work engineered the IS621 recombinase system for human genome editing by optimizing the IS621 protein and its bridge RNA (bRNA) to enable precise, scarless insertion of large DNA fragments. The authors developed enIS621-tebRNA, demonstrating site-specific, scarless large-fragment integration in human cells with systematic evaluation of insertion efficiency. Scientifically and therapeutically, this expands the toolkit for accurate large-DNA genomic integration, which is a key limitation for many gene and cell therapy strategies.

Guo J, Song Z, Wang W et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Metformin for COVID-19: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

A systematic review and meta-analysis of randomized controlled trials assessed whether metformin improves clinical outcomes and safety in adults with COVID-19. Across four RCTs, metformin did not significantly reduce the composite outcome including hospitalization and emergency department (ED) visits (and related endpoints as reported in the truncated abstract). Clinically, the evidence suggests metformin is not clearly beneficial for COVID-19 outcomes in the studied RCT population, highlighting the need for larger or more targeted trials.

Tahir T, Siddique MA, Ijaz K et al. · Reviews in medical virology · (2026) · View on PubMed ↗

Silk-Based Protein Corona Enhances mRNA-LNP Vaccine Efficacy and Prevents Tumor Relapse.

The study engineered a post-fabrication custom protein corona on mRNA lipid nanoparticles (mRNA-LNPs) using cationic silk fibroin (SF) and tested delivery and efficacy in preclinical cancer vaccine models. SF-coated LNPs increased cellular uptake and endosomal escape, yielding 3.6-fold higher lymph node delivery and 2.5-fold longer in vivo protein expression than unmodified LNPs, and improved dendritic cell maturation and tumor control (with prevention of tumor relapse reported in the truncated abstract). This suggests silk-fibroin protein corona engineering could be a practical strategy to enhance lymph node targeting and durability of mRNA vaccine responses beyond liver/lung/spleen tropism.

Cui S, Ye Z, Arral ML et al. · Advanced materials (Deerfield Beach, Fla.) · (2026) · View on PubMed ↗

Multi-epitope mRNA vaccine and protein vaccine protect mice against Toxoplasma gondii.

This study developed and tested a multi-epitope chimeric antigen T-SGR (targeting Toxoplasma gondii SAG1, GRA7, and ROP16) delivered as an mRNA lipid nanoparticle (LNP) vaccine or as a recombinant protein vaccine in C57BL/6 mice. Both vaccine formats generated protective immune responses and protected mice against T. gondii challenge. The findings support multi-antigen mRNA-LNP vaccination as a promising strategy for toxoplasmosis prevention.

Cui Y, Qu H, Zhou C et al. · Parasites & vectors · (2026) · View on PubMed ↗ · Free PDF ↗

Cardiovascular prevention and cardiometabolic risk indices

This CHARLS cohort study (2011–2020) evaluated whether the triglyceride-glucose index–body shape index (TyG-ABSI) predicts incident cardiovascular disease in CVD-free Chinese adults and compared its prognostic performance with other TyG-related obesity indices. TyG-ABSI showed incremental long-term predictive value for CVD risk over conventional TyG and obesity metrics in this East Asian adiposity phenotype. These findings support TyG-ABSI as a practical, lipid–glucose–morphology–based risk stratification tool for cardiovascular prevention in Chinese populations.

Liu X, Yang S, Fu Q et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗

Rehmannioside D prevents estrogen-deficiency induced osteoporosis by interacting with c-Jun to dismantle the AP-1 complex and suppress MAPK/NF-κB signaling.

This study used network pharmacology plus in vitro experiments to test rehmannioside D (RD) against estrogen-deficiency induced osteoporosis by targeting c-Jun and disrupting the AP-1 complex, thereby suppressing MAPK/NF-κB signaling. RD inhibited RANKL-induced osteoclast differentiation and function in bone marrow-derived macrophages (BMDMs), with target engagement supported by Cellular Thermal Shift Assay and related validations. Mechanistically, RD may represent a multi-pathway anti-osteoporotic candidate that reduces osteoclastogenesis via c-Jun/AP-1 and MAPK/NF-κB axis modulation.

Wang Y, Wu J, Liu H et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

Evolocumab in Patients With High-Risk Diabetes: Results From the VESALIUS-CV Trial.

This prespecified analysis of the VESALIUS-CV randomized trial evaluated the PCSK9 inhibitor evolocumab (140 mg every 2 weeks) for preventing first cardiovascular events in high-risk diabetes patients without prior myocardial infarction or stroke. Evolocumab reduced the risk of the dual primary composite endpoint of coronary heart disease death and myocardial infarction compared with placebo (full results were truncated in the abstract). These findings support PCSK9 inhibition as a preventive cardiovascular strategy in diabetes patients at high baseline risk.

Leiter LA, Giugliano RP, Marston NA et al. · Diabetes care · (2026) · View on PubMed ↗

Association of the CHG Index with the onset, progression, and prognosis of cardiovascular-kidney-metabolic syndrome: findings from two large prospective cohorts.

This analysis of two large prospective cohorts evaluated whether the CHG index (cholesterol, HDL, and glucose composite burden) predicts onset, stage-wise progression, and prognosis of cardiovascular-kidney-metabolic (CKM) syndrome. In UK Biobank, Fine-Gray proportional subdistribution hazards models assessed associations between CHG levels and incident cardiovascular disease, chronic kidney disease, and type 2 diabetes outcomes (full results truncated). If robust, the CHG index could enable earlier identification of individuals at higher risk for CKM syndrome and guide risk-stratified prevention.

Zhao Z, Bai Y, Ma C et al. · Diabetology & metabolic syndrome · (2026) · View on PubMed ↗ · Free PDF ↗

Associations of cumulative exposure and dynamic trajectories of the combined atherogenic and frailty index with incident cardiometabolic multimorbidity: a longitudinal analysis based on the China Health and Retirement Longitudinal Study (CHARLS).

This longitudinal analysis used data from 7,995 participants in the China Health and Retirement Longitudinal Study (CHARLS) to evaluate how baseline levels, cumulative exposure, and longitudinal trajectories of the combined atherogenic index of plasma–frailty index (AIPFI) relate to incident cardiometabolic multimorbidity (CMM). Higher cumulative AIPFI and unfavorable longitudinal trajectories were associated with increased risk of developing CMM. These results support AIPFI as a composite risk marker that captures both atherogenic dysregulation and frailty-related vulnerability for predicting future cardiometabolic multimorbidity.

Feng X, Deng B, Pan Y et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Plasma neurofilament light chain in early Parkinson’s disease predicts motor complications: a prospective cohort study.

This prospective longitudinal cohort study followed 173 patients with early-stage Parkinson’s disease for up to seven years to determine whether baseline and longitudinal plasma biomarkers predict motor complications. Using an ultrasensitive single-molecule array platform, plasma neurofilament light chain (NfL) (along with GFAP, p-tau181, and Aβ species) was measured at baseline, 1 year, and 2 years, and NfL predicted the development of motor complications such as motor fluctuations and dyskinesias. The findings support plasma NfL as a clinically useful prognostic biomarker for anticipating motor complication risk early in Parkinson’s disease.

Che N, Huang J, Wang S et al. · NPJ Parkinson’s disease · (2026) · View on PubMed ↗ · Free PDF ↗

Colchicine in cardiovascular medicine: Current perspectives on mechanisms and clinical therapeutics.

This review evaluated the mechanistic basis and clinical trial evidence for colchicine as a cardiovascular therapeutic across multiple diseases, including pericarditis and atherosclerotic coronary artery disease. It reports that randomized trials support colchicine’s efficacy in reducing recurrences of acute and recurrent pericarditis and that long-term low-dose colchicine reduces major adverse cardiovascular events in chronic coronary syndromes, though results are not uniformly consistent across all studies. The review supports colchicine repurposing in selected cardiovascular settings while emphasizing the need to clarify patient selection and reconcile trial heterogeneity.

Ding H, Cheng CK, Jiang M et al. · Pharmacology & therapeutics · (2026) · View on PubMed ↗

A body roundness index (BRI)-based predictive model for metabolic syndrome in perimenopausal and postmenopausal women-from a cross-sectional machine learning study to a longitudinal dynamic assessment.

This cross-sectional machine learning study with longitudinal dynamic assessment developed a Body Roundness Index (BRI)-based predictive model for metabolic syndrome (MetS) in perimenopausal and postmenopausal women. Using NHANES 2007–2020 for training and validation in a Dalian University affiliated hospital cohort (2023–2024), the model selected predictors via LASSO and Boruta and aimed to improve MetS risk prediction in this population. The work is clinically relevant because it proposes a practical anthropometric tool (BRI) to identify MetS risk in midlife women, potentially enabling earlier prevention of cardiovascular and diabetes outcomes.

Xi Y, Sun Q, Han Y et al. · Annals of medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Association of inflammation with sex hormones and vitamin D in women: Findings from NHANES (2021-2023).

Using NHANES 2021–2023 data from 3179 U.S. women aged 18–80 years, this cross-sectional study assessed associations between systemic inflammation (hs-CRP quartiles) and sex hormones and vitamin D (25-hydroxyvitamin D3). It reports that women in the highest hs-CRP quartile had higher age and body weight and then used multivariable linear regression to test independent relationships between hs-CRP and endocrine markers after confounder adjustment. The significance is that it links inflammation with endocrine and vitamin D status in women, informing hypotheses about inflammatory pathways in health and disease risk.

Abu-Zaid A, Baradwan S, Adly HM et al. · Scottish medical journal · (2026) · View on PubMed ↗

In a population-based UK Biobank cohort of 362,656 participants followed for a median of 13.65 years, this study assessed whether age-related musculoskeletal diseases (ARMDs)—including sarcopenia, osteoporosis, and osteoarthritis—are associated with subsequent Parkinson’s disease (PD) risk. Using Cox models adjusted for demographic, lifestyle, and genetic factors (with subgroup/sensitivity analyses and a nested case-control component), it tested both individual and cumulative ARMD associations with PD. The significance is that it clarifies whether ARMD burden could serve as an epidemiologic risk marker for PD and potentially inform prevention strategies.

Yang T, Huang J, Xiao Y et al. · The journals of gerontology. Series A, Biological sciences and medical sciences · (2026) · View on PubMed ↗

Extracellular Vesicles Reflect Thrombo-Inflammatory, Endothelial and Tissue-Remodelling Changes in Cirrhosis.

This prospective single-centre study measured circulating extracellular vesicles (EVs) from platelet-poor plasma in patients across compensated, stable decompensated, and acutely decompensated cirrhosis, using flow cytometry to quantify platelet-, endothelial-, immune-, and CK18+ EV subsets. EV profiles were assessed for their ability to reflect thrombo-inflammation, endothelial dysfunction, tissue remodeling, and to predict liver-related outcomes and disease severity (details truncated). If validated, EV subset quantification could provide clinically actionable biomarkers for risk stratification in cirrhosis.

Campello E, Zanetto A, Ferdinande K et al. · Liver international : official journal of the International Association for the Study of the Liver · (2026) · View on PubMed ↗

Gut-derived bacterial extracellular vesicles: the microbial dark matter contributing to host inflammation and cardiometabolic disease.

This review article synthesized evidence on gut-derived bacterial extracellular vesicles (BEVs) as mediators of interkingdom communication that influence host inflammation and cardiometabolic disease. BEVs carry proteins, lipids, nucleic acids, and pathogen-associated molecular patterns that engage host pattern recognition receptors (PRRs) to modulate immune and metabolic responses and can cross intestinal barriers (mechanistic details truncated). The work highlights BEVs as potential targets for diagnostics or therapies aimed at reducing chronic inflammation driving cardiometabolic disease.

Oliver B, Sun M, Lee YS et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

STING promotes CD8 T-cell cardiotropism and fibrosis from distinct cellular compartments in doxorubicin cardiomyopathy.

This study examined how the STING (stimulator of interferon genes) pathway drives CD8 T-cell cardiotropism and fibrosis in doxorubicin (DR) cardiomyopathy using in vivo and in vitro models. DR activated STING in distinct cardiac compartments—cardiac fibroblasts, endothelial cells, and myeloid cells—and myeloid STING was required for the CD8 T-cell recruitment/response that contributes to cardiotoxicity (key mechanistic outcomes truncated). Targeting compartment-specific STING signaling could represent a strategy to mitigate DR-induced cardiac fibrosis and immune-mediated injury.

Bayer AL, Zambrano MA, Emig R et al. · Cardiovascular research · (2026) · View on PubMed ↗

Comparative efficacy and safety of transcatheter edge-to-edge repair versus tricuspid valve replacement versus optimal medical therapy in moderate-to-severe tricuspid regurgitation: a network meta-analysis of randomized controlled trials.

This network meta-analysis compared transcatheter edge-to-edge repair (TEER), transcatheter tricuspid valve replacement (TTVR), and optimal medical therapy (OMT) for moderate-to-severe tricuspid regurgitation using randomized controlled trials. The analysis synthesized RCT evidence to estimate relative efficacy and safety across interventions for patients who remained symptomatic despite OMT. Clinically, this helps rank less-invasive transcatheter options versus surgery-adjacent replacement strategies to guide treatment selection in TR.

Veettil INK, Jamandlamudi A, Khader NA et al. · Journal of cardiothoracic surgery · (2026) · View on PubMed ↗ · Free PDF ↗

Generated automatically on June 08, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.

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PubMed Trending Research Digest — June 08, 2026

PubMed Trending Research Digest — June 08, 2026

Overview

Asthma endotypes and airway biomarkers

Effects of inhaled nitric oxide on ventilation/perfusion mismatch assessed by electrical impedance tomography in intubated patients with moderate-to-severe ARDS: a prospective physiological study.

Type 2 Endotypes in Airway Diseases.

The 2025 ATS/ERS update of the international multidisciplinary classification of the interstitial pneumonias: implications for the pathologist.

Lung cancer diagnosis, staging, and procedural advances

Advances in Diagnosis-Pulmonology.

Obesity and metabolic subphenotypes (including GLP-1/dual agonists)

Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial.

Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-controlled, phase 3a study.

Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study.

Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial.

Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial.

Plasma Aryl Hydrocarbon Receptor Agonist Activity Is Associated With Inflammation and Metabolic Dysregulation in Obesity: A Cross-Sectional Study.

Time-restricted eating versus dietetic guidance on glycaemic outcomes in adults at risk of type 2 diabetes: a non-inferiority randomised clinical trial.

A subphenotype of obesity with reduced enteroendocrine GLP-1 synthesis and enhanced tirzepatide response.

Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.

Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Events in Adults With Obesity and Autoimmune Disease: A Target Trial Emulation.

Interplay Between the Ketogenic Diet and the Gut Microbiome in Glioblastoma: A Comprehensive Review of Mechanisms and Clinical Implications.

Genetic mechanisms and molecular stratification in rare GI disorders

PRDM9 Deficiency Drives Mosaic Promoter Deletions in Sporadic Hirschsprung Disease and Supports Blood-based Molecular Stratification.

Novel variants in YTHDC2 cause non-obstructive azoospermia by disrupting the mitotic-to-meiotic transition in humans and mice.

Mechanisms and evidence for manual/physical therapies

Manual Therapy Treatment Mechanisms are Complex: Challenges and a Call to Action.

Impact of long COVID on health-related quality-of-life among Japanese adults: findings of CARE Japan study.

Hyperbaric oxygen therapy improves clinical symptoms and functional capacity and modulates thalamic connectivity in ME/CFS: a prospective cohort study.

Aging biology via iron, senescence, and ferroptosis

Fenofibrate attenuates hyperhomocysteinemia-potentiated thrombosis by restoring platelet fatty acid β-oxidation.

MCCC2 stabilizes LTBP1 via suppressing SMURF1-dependent ubiquitination to drive bone metastasis in prostate cancer.

Proteomic clocks combined with deep learning phenotypes track eye aging and diseases.

Ameliorating calcium homeostasis improves longevity and healthspan in progeroid and naturally aged mice.

Ferro-Aging: A Novel Paradigm Linking Iron Overload, Lipid Peroxidation and Cellular Senescence.

ATOX1 deficiency induces memory impairment via promoting cuproptosis in Alzheimer’s disease.

Effect of six weeks ubiquinol supplementation on mitochondrial respiratory function and exercise capacity in healthy males.

Dissecting Immune Cell Ferroptosis via Single-Cell Multi-Omics Identifies RPL8 as a Potential Therapeutic Target for Depression.

Overcoming redundancy in the Arabidopsis TREHALOSE-6-PHOSPHATE PHOSPHATASE family reveals connections to development and iron homeostasis.

Endoscopy and gastrointestinal procedural therapeutics

A peptide-first hemostatic strategy for oozing-type post-sphincterotomy bleeding during ERCP: a multicenter noninferiority randomized controlled trial (PROTECT-EST).

Intraocular Pressure Changes Following Intraluminal Stent Removal from the Paul Glaucoma Implant: A Systematic Review and Meta-Analysis.

Clinical outcomes of endoscopic resection for remnant gastric cancer: a multicenter prospective cohort study.

Intraoperative measurement of breast-conserving surgery margins: surgical application.

The effects of mechanical ventilation during v-a ecmo support: a systematic review.

Genetic risk and biomarkers in liver disease (MASLD/PBC/MASH)

PNPLA3 polymorphisms and risk of hepatic and extrahepatic outcomes in MASLD: a meta-analysis of observational studies.

Steatotic Liver Disease at Primary Biliary Cholangitis Diagnosis: Association With Ursodeoxycholic Acid Response and Outcomes.

Tumor microenvironment and immune cell targeting in cancer

Septin multimer autoantibodies in severe motor neuropathy mimicking lower motor neuron disease.

Herpesvirus Retinitis by Immune Status: Clinical Phenotypes and Predictors of Retinal Detachment and Severe Visual Impairment.

Cancer-associated and non-neoplastic fibrosis: Comparative mechanisms and emerging antifibrotic strategies.

Integrative single-cell and spatial transcriptomics analysis reveals a baicalein-responsive 10-gene signature for non-small cell lung cancer.

Structure-Informed Design of Distinct Parallel G-Quadruplex Stabilizers for KRAS-Driven Cancer Therapy.

Comprehensive multi-omics pan-cancer analysis revealed that ANTXR1 is a potential biomarker for diagnosis and immunotherapy.

RAD21 regulation of the enhancer-promoter chromatin loop of RAD51 promotes PARPi resistance in ovarian cancer.

NOTCH3 regulates myofibroblastic CAF differentiation via the P62-ROS signaling axis to promote bladder cancer progression.

Identification of macrophage polarization-related genes for esophageal cancer risk: a multi-omics Mendelian randomization analysis.

Association of baseline immune cell composition with CAR-T cell expansion and survival in Relapsed/Refractory large B-Cell lymphoma.

SERPINE2-mediated activation of JAK2/STAT3 facilitates NRF2 nuclear translocation and GCLC transcription to confer ferroptosis resistance and lenvatinib resistance in hepatocellular carcinoma.

Decoding TNF receptor superfamily control of CD4+Foxp3+ Regulatory T cell-mediated tolerance: implications for the treatment of graft‑versus‑host disease.

Anti-NRP1 peptide-engineered ROS/pH dual-responsive nanoparticles for Alpelisib delivery regulate Sema3A-NRP1/PI3K-AKT signaling to balance oxidative stress and inhibit angiogenesis in endometriosis.

LncRNA 606938-TFAM axis drives oxidative stress and activates cGAS-STING pathway-mediated antitumor immunity to restrain colorectal cancer progression.

Impact of fludarabine dosage on outcomes in large B-cell lymphoma patients treated with CAR T-cell therapy: a retrospective study of the CTIWP of the EBMT.

Discovery of BEND4 as a novel single-gene prognostic marker and therapeutic target for adverse AML.

IQGAP3 bridges matrix stiffness with glioma stem cell maintenance and radioresistance by stabilizing SOX2.

Multi-omic profiling identifies TREM2+ lipid-laden macrophages as inflammatory drivers and therapeutic targets of colorectal cancer liver metastasis.

Targeting C/EBPβ/SCD1/C16:1 loop-driven macrophage M2 polarization by Bruceine D improves anti-PD-1 immunotherapy in colorectal cancer.

Targeting BRD4 to reverse organ fibrosis: Epigenetic regulation, cellular plasticity, and therapeutic potential.

Dysregulated transcription in core- and pol-specific CD8 T cells can be targeted by HDAC inhibition to improve T-cell function in chronic hepatitis B.

PAD4-mediated citrullination of IGF2BP2 stabilizes MCM mRNAs to drive intrahepatic cholangiocarcinoma progression.

Multimodal Artificial Intelligence Prediction of Abiraterone Efficacy in Two STAMPEDE Phase 3 Trials of Non-Metastatic Very High-Risk Prostate Cancer.

Transcription factors as drivers of 3D enhancer-promoter interactions.

SLC22A3/OCT3 drives serotonin-mediated stemness in pancreatic cancer.

TRIM47 drives metabolic reprogramming and tumor progression in Nasopharyngeal Carcinoma via K48-linked ubiquitination and degradation of SDHB.

Single-cell immunoprofiling reveals a dysfunctional-like immune microenvironment and malignant phenotype in aging penile squamous cell carcinoma.

Real-world outcomes of [177Lu]Lu-PSMA-I&T in [18F]FDG-positive metastatic castration-resistant prostate cancer: factors related to response and survival.

Machine learning models predict the immunotherapy response in tumors on the basis of DNA methylation.

“Outstanding” ADC Candidates Emerge for SCLC, Other Cancers.

Autoimmune nodopathy associated with contactin-2 antibodies manifesting as Guillain-Barré syndrome: a case report.

Microglial galectin-3 disrupts parvalbumin interneurons and hippocampal synchrony, driving cognitive deficits.