PubMed Trending Research Digest — June 23, 2026

Automated digest · 100 articles · 15 research areas · June 23, 2026

Overview

This week’s papers cluster around a shared translational theme: moving from broad risk signals to mechanism-informed stratification and targeted intervention. Across cardiometabolic disease, multiple studies refine prediction using routinely measurable indices (e.g., insulin-resistance surrogates, CTI/CTI-CVAI, visceral fat burden) and show that timing of treatment after T2D diagnosis can materially affect downstream cardiovascular outcomes. In parallel, several neurodegeneration studies emphasize biomarkers and clearance biology (CSF-mediated clearance, TMEM106B, plasma proteomics tied to amyloid) and connect them to cell-type-specific mechanisms that could guide future therapeutics.

On the oncology and immunology front, the dominant message is that resistance and immune escape are not “mysteries” but tractable biology. Mechanistic work links specific genomic alterations to acquired drug resistance (e.g., EML4-ALK driving KRAS G12C inhibitor resistance) and suggests rational combination strategies. Other studies map how metabolic-epigenetic states and innate immune signaling (lactylation–cGAS/STING, MAM-driven inflammasome regulation, mitophagy–NAD/SIRT1 axes) shape inflammation and tumor/host responses—opening new intervention points. Finally, in infectious and inflammatory disease, host–microbe axes (AhR–IL-22 with Sutterella; autophagy/lipid dependencies in Toxoplasma; Treg plasticity in recurrent malaria) reinforce the idea that manipulating specific immune pathways may be more effective than broad suppression.

Overall, the digest reflects a field-wide shift toward “precision across systems”: integrating omics, imaging, and longitudinal cohorts to identify who is at risk and why, then using that mechanistic understanding to design therapies—whether that’s individualized ventilation strategies in ARDS, BBB-penetrant GLP-1R agonists for Alzheimer’s, or next-generation targeted agents and engineered delivery platforms in cancer.

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Cancer genomics & transcriptomics (IDH, RNA isoforms, biomarkers)

Integrating MRI radiomics and transcriptomics to predict IDH mutation status and prognosis in glioma.

This study integrated MRI radiomics with transcriptomic gene data to predict IDH mutation status and prognosis in glioma using TCIA MRI datasets and RNA-seq differential expression analyses. Radiomics feature selection (including Mann–Whitney U testing and LASSO regression) combined with key IDH-linked genes produced models validated in internal and external cohorts. The approach supports a more biologically informed, noninvasive framework for IDH stratification and prognostication in glioma.

Zhong RD, Li Q, Wang H et al. · Cancer cell international · (2026) · View on PubMed ↗ · Free PDF ↗

The expression landscape and clinical significance of cancer-specific RNA transcripts across human cancers.

This study used long-read sequencing to map the expression landscape of cancer-specific RNA transcripts (cancer-SRTs) across human cancers, analyzing 44,405 cancer-SRTs. It characterized transcript-level patterns using dimensionality reduction (e.g., t-SNE) and linked cancer-SRT expression to clinical relevance across multiple cancer types. The work provides a broadly applicable resource for identifying transcript targets that may enable more precise, transcript-informed therapeutic strategies.

Li H, Ding J, He X et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer imaging & machine learning risk prediction (radiomics, heterogeneity, trajectories)

Biology-informed risk stratification of glioblastoma by integrating MRI-based intratumoral heterogeneity with clinical features: a multicenter validation study.

This multicenter validation study developed a biology-informed glioblastoma risk stratification model by combining MRI-based intratumoral heterogeneity with routinely available clinical features. The resulting online-accessible prognostic platform stratified patients into risk groups with clinically meaningful outcome differences while providing biological interpretability tied to intratumoral heterogeneity. This could improve pre-randomization balance and guide individualized trial enrollment or treatment decisions in glioblastoma.

Zhang J, Guo H, Ma X et al. · Experimental hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Nab-paclitaxel plus S-1 induction chemotherapy for patients with locally advanced pancreatic cancer: a multicenter, open-label phase 2 study.

This multicenter, open-label phase 2 trial evaluated nab-paclitaxel plus S-1 (SnP) as first-line induction chemotherapy in 60 patients with locally advanced pancreatic cancer (LAPC) across four centers in China. The study used 6-month progression-free survival (PFS) as the primary endpoint and assessed safety and efficacy after up to eight cycles of nab-paclitaxel with S-1 followed by investigator-selected continuation. The trial informs clinical feasibility and potential benefit of combining nab-paclitaxel with S-1 for LAPC where outcomes remain poor.

Cao Z, Qiu J, Luo W et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer therapeutics & resistance mechanisms (targeted therapy, combinations, relapse)

Cuproptosis-immunity crosstalk informs strategy to overcome immunotherapy resistance.

This work studied how cuproptosis intersects with antitumor immunity and immunotherapy resistance, focusing on copper-dependent cell death requiring ferredoxin 1 (FDX1)-mediated protein lipoylation. It found that CD8+ T cell-mediated antitumor immunity increases tumor susceptibility to cuproptosis in immunocompetent hosts, and that cuproptotic tumor cells trigger immunogenic cell death that activates dendritic cells via damage-associated molecular patterns. The results suggest combining cuproptosis inducers with immunotherapy could overcome resistance by converting tumor cell death into a stronger immune-activating signal.

Lei G, Lu Z, Xu Z et al. · Cell · (2026) · View on PubMed ↗

EGFR N-Glycosylation Catalyzed by NDST2 Promotes Lenvatinib Resistance in Hepatocellular Carcinoma.

This study investigated mechanisms of lenvatinib resistance in hepatocellular carcinoma (HCC) using patient-derived organoids (PDOs) and orthotopic xenograft models, focusing on EGFR glycosylation. Resistant PDOs showed increased N-glycosylation of EGFR correlated with higher EGFR protein expression, implicating NDST2-catalyzed EGFR N-glycosylation in resistance. The work suggests that disrupting NDST2-driven EGFR glycosylation could sensitize HCC to lenvatinib and improve outcomes.

Gu H, Li F, Chen Y et al. · Cancer research · (2026) · View on PubMed ↗

EML4-ALK mediates resistance to KRAS G12C inhibition and induces an oncogenic dependency by rewiring signaling through the wild-type RAS pathway.

This Cancer Discovery study investigated mechanisms of acquired resistance to KRAS G12C inhibitors in lung adenocarcinoma (LUAD) tumors that develop an EML4-ALK fusion, using experimental models to test targeted pathway inhibition. The key finding was that EML4-ALK mediates resistance to KRAS G12C inhibition and creates an oncogenic dependency that can be overcome by combined ALK and KRAS G12C inhibition. This provides a mechanistic rationale for combination targeted therapy in KRAS G12C–mutant cancers with emergent EML4-ALK fusions.

Scaparone P, Mira A, Cheong TC et al. · Cancer discovery · (2026) · View on PubMed ↗

Enhanced exosome biomanufacturing, precision isolation, and advanced engineering: toward mechanistic regulation and biomaterial integration for osteoarthritis therapy.

This review summarizes advances in exosome biomanufacturing, including genetic modifications and optimized culture conditions to enhance exosome yield, and compares precision isolation/purification approaches such as ultracentrifugation and size-exclusion chromatography. It reports that engineered exosomes can be integrated with biomaterials and tailored for drug delivery, with electroporation and other engineering methods used to load therapeutic cargo and improve targeting. The scientific significance is that scalable, mechanistically informed exosome production and engineering could accelerate effective osteoarthritis therapies.

Gao M, Yin Q, Zhong Z et al. · Journal of nanobiotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

Direct Androgen Receptor Antagonism Enhances Therapeutic PSMA Radioligand Uptake in Prostate Cancer Models.

This preclinical study tested whether direct androgen receptor (AR) antagonism improves uptake of PSMA-targeted radioligands in prostate cancer models. In AR-positive LNCaP and C4-2 cells and AR-negative PC3 PSMA+ models, treatment with direct AR antagonists enzalutamide and apalutamide (compared with androgen biosynthesis inhibition using abiraterone) enhanced PSMA surface expression and increased functional therapeutic radioligand uptake. The significance is that the mode of AR pathway inhibition may be optimized to improve PSMA radioligand theranostic performance in prostate cancer.

Hartrampf PE, Serfling SE, Hasenauer N et al. · Molecular imaging and biology · (2026) · View on PubMed ↗ · Free PDF ↗

A decade of progress in small-cell lung cancer (2015-2025): a narrative review.

This narrative review summarizes therapeutic progress in small-cell lung cancer (SCLC) from 2015 to 2025, focusing on changes beyond the earlier standard of platinum–etoposide chemotherapy with thoracic radiotherapy and prophylactic cranial irradiation (PCI). It synthesizes key advances from 2015–May 2025, including major trial-driven developments in systemic therapy and radiotherapy strategies for both extensive-stage (ES-SCLC) and limited-stage (LS-SCLC) disease. The clinical significance is that it provides an up-to-date framework for how evolving evidence has changed treatment expectations and decision-making in SCLC.

Petrelli F, Dottorini L, Ghidini A et al. · European journal of clinical pharmacology · (2026) · View on PubMed ↗

A unified platform for the rapid assembly of glutarimides for Cereblon E3 ligase modulatory drugs.

This medicinal chemistry study developed a unified organocatalytic synthesis platform to rapidly assemble glutarimide-containing Cereblon (CRBN) ligands used in PROTACs, molecular glues, and CELMoDs. The key advance is a streamlined, modular route designed to overcome multistep bottlenecks that limit rapid SAR and late-stage diversification of glutarimide scaffolds. The platform accelerates generation of CRBN-modulating degraders, potentially speeding discovery of next-generation targeted protein degradation therapeutics.

Whalley DM, Lorthioir O, Anderson NA et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Identifying druggable proteins of the association of chronotype on breast cancer using Mendelian randomization.

This Mendelian randomization study used a two-step approach to identify circulating protein mediators of the association between chronotype (morning vs other) and breast cancer risk. Using European-ancestry UK Biobank and 23andMe genetic data for chronotype, SomaScan-measured plasma proteins in Icelandic individuals, and Breast Cancer Association Consortium breast cancer outcomes, it pinpointed specific druggable proteins that may causally mediate chronotype-related breast cancer susceptibility. These results provide candidate therapeutic targets and mechanistic clues for how circadian biology could influence breast cancer development.

Luo S, Ai Y, Zheng J et al. · Communications medicine · (2026) · View on PubMed ↗ · Free PDF ↗

SGI-7079 as a novel type I FLT3 inhibitor overcomes resistance to gilteritinib and quizartinib mediated by ITD and TKD mutations in acute myeloid leukemia.

The study evaluated SGI-7079, a novel type I FLT3 inhibitor, for its ability to overcome resistance to gilteritinib and quizartinib driven by FLT3 ITD and secondary TKD mutations in acute myeloid leukemia (AML). SGI-7079 inhibited proliferation of AML cell lines harboring FLT3-ITD and multiple resistant TKD mutations (including D835), indicating broader activity against resistance genotypes. This supports SGI-7079 as a potential next-generation therapeutic strategy for FLT3-mutant AML patients who develop resistance to current type I/II FLT3 inhibitors.

Zhong Z, Xie M, Wang S et al. · NPJ precision oncology · (2026) · View on PubMed ↗ · Free PDF ↗

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Hematologic malignancies (CLL, AML, myelofibrosis, myeloma, transplant)

Non-myeloablative versus reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients aged ≥65: a study from the ALWP of EBMT.

This EBMT ALWP retrospective study compared non-myeloablative (NMA) versus reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation in 2,900 acute myeloid leukemia (AML) patients aged ≥65 in complete remission. It found differences in outcomes between conditioning intensities, including overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM), and rates of acute/chronic graft-versus-host disease (GVHD) and GRFS. The significance is that conditioning intensity selection for elderly AML patients can be informed by comparative outcome data to balance relapse risk and transplant toxicity.

Kanellopoulos A, Labopin M, Spyridonidis A et al. · Bone marrow transplantation · (2026) · View on PubMed ↗

Primary Myelofibrosis (PMF)-The German ONKOPEDIA Guideline 2025.

This guideline article summarized the German ONKOPEDIA 2025 recommendations for diagnosis and management of primary myelofibrosis (PMF), a clonal hematopoietic stem cell disorder driven largely by JAK2 signaling. It contextualized PMF within related entities (post-PV-MF and post-ET-MF) and incorporated updated WHO/ICC diagnostic criteria published in 2022. Clinically, it provides an evidence-based framework for standardized evaluation and treatment decisions in MF patients.

Griesshammer M, Al-Ali HK, Baerlocher GM et al. · International journal of cancer · (2026) · View on PubMed ↗

An indirect comparison of pirtobrutinib with second-generation covalent Bruton tyrosine kinase inhibitors in BTKi naive, and relapsed-refractory chronic lymphocytic leukemia: results of a network meta-analysis.

This Bayesian network meta-analysis compared pirtobrutinib with second-generation covalent BTK inhibitors (acalabrutinib and zanubrutinib) for BTK inhibitor–naive and relapsed/refractory chronic lymphocytic leukemia (CLL) using randomized trials linked by a common comparator (ibrutinib). Across 814 patients, pirtobrutinib showed efficacy comparable to acalabrutinib and zanubrutinib with no statistically significant differences in progression-free survival (PFS) versus acalabrutinib (HR 0.73, 95% CrI 0.44–1.20). These comparative effectiveness results help position pirtobrutinib for BTKi-naive and R/R CLL where direct head-to-head trials are lacking.

Molica S, Giannarelli D, Allsup D · Leukemia & lymphoma · (2026) · View on PubMed ↗

Real-world evidence on infection risk in multiple myeloma treated with BiTEs and CAR-T cells: a meta-analysis.

This meta-analysis systematically reviewed real-world retrospective studies of adult relapsed/refractory multiple myeloma (RRMM) patients treated with approved bispecific T-cell engagers (BiTEs) or CAR-T cell therapies to quantify severe (grade 3–4) infection risk. Pooled event rates showed clinically meaningful rates of severe infections in heterogeneous real-world populations, emphasizing that infection risk may differ from clinical-trial settings. The results provide safety benchmarks for clinicians and inform monitoring and prophylaxis strategies for infection in RRMM patients receiving BiTEs/CAR-T.

Spataro F, Desantis V, Dicuonzo G et al. · Experimental hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Pomalidomide-induced acute eosinophilic pneumonia: a case report.

This case report described a 67-year-old patient who developed pomalidomide-induced acute eosinophilic pneumonia during treatment with pomalidomide for relapsed/refractory multiple myeloma. The clinical presentation and attribution supported eosinophilic lung injury as an uncommon but serious adverse effect of pomalidomide. The report highlights the need for vigilance for pulmonary toxicity in patients receiving immunomodulatory drugs, especially when respiratory symptoms emerge.

Megevet M, Freitas Pereira J, Vervier J et al. · BMC pulmonary medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Clinical benefit of palbociclib retreatment after abemaciclib exposure in hormone receptor positive, HER2 negative metastatic breast cancer.

This retrospective clinical study evaluated the clinical benefit of CDK4/6 inhibitor retreatment after prior abemaciclib exposure in 78 patients with hormone receptor–positive, HER2-negative metastatic breast cancer (HR+/HER2− MBC), comparing treatment sequences (abemaciclib→abemaciclib, abemaciclib→palbociclib, and palbociclib→abemaciclib). Patients receiving retreatment with a CDK4/6 inhibitor after earlier abemaciclib exposure showed measurable clinical benefit, with outcomes varying by retreatment sequence. These findings inform real-world decision-making on whether and how to reuse CDK4/6 inhibitors after progression or toxicity on prior agents.

Yu M, Yamashita M, Takada M et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

Interpretable machine learning model for predicting kidney failure among CAKUT children in multicenter large-scale study.

This multicenter study developed and validated POCC, an interpretable machine-learning model to predict kidney failure risk at 1, 3, and 5 years in children with congenital anomalies of the kidney and urinary tract (CAKUT). POCC achieved high discrimination with internal AUCs of 0.93–0.99 and external AUCs up to 0.89–0.98 (pediatric/general hospital validations), with a specialized version incorporating congenital-hereditary features. Clinically, POCC could enable earlier, individualized risk stratification for CAKUT progression and support more targeted monitoring and intervention.

Liu T, Wang H, Liu J et al. · NPJ digital medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Immunotherapy, immune regulation & host–pathogen interactions

Memory regulatory T cells reprogram into protective TFH cell-like effectors in recurrent malaria.

The study examined how memory regulatory T (mTreg) cells behave during recurrent Plasmodium infection in humans and mice, focusing on their antigen-driven expansion and epigenetic reprogramming upon reinfection. It found that mTreg cells transition from FOXP3+ immunosuppressive cells into protective TFH-like effector cells that support germinal center responses and better control parasitemia. This mechanistically links Treg plasticity to improved immunity in recurrent malaria and suggests that targeting Treg-to-TFH reprogramming could enhance vaccine or immunotherapy strategies.

Charles-Chess NAE, Ruberto AA, Bowers C et al. · Nature immunology · (2026) · View on PubMed ↗

Beyond viral suppression: combining PEG-interferon with novel immunotherapies for functional cure of chronic hepatitis B.

This review/article discussed strategies for functional cure of chronic hepatitis B (CHB) by moving beyond viral suppression, focusing on combining pegylated interferon-α (PEG-IFN-α) with novel immunotherapies. The key point is that PEG-IFN-α can enhance antigen presentation and partially restore HBV-specific T cell function, which may complement immunotherapies aimed at overcoming immune tolerance driven by persistent covalently closed circular DNA (cccDNA) and integrated HBV DNA. The proposed combination approach is significant because it targets both viral persistence and immune exhaustion—two major barriers to CHB functional cure.

Wang Q, Deng W, Wang S et al. · Frontiers in cellular and infection microbiology · (2026) · View on PubMed ↗ · Free PDF ↗

First-in-human, phase I, randomized, safety, pharmacokinetic, food-effect and pharmacodynamic study of a tyrosine kinase 2/Janus kinase 1 inhibitor, SDC-1801.

This first-in-human, randomized phase I study evaluated the oral TYK2/JAK1 inhibitor SDC-1801 in 95 healthy adult participants, assessing safety, tolerability, pharmacokinetics, food-effect, and pharmacodynamics. The study reported no deaths or treatment-related serious adverse events and characterized dose-dependent exposure and pharmacodynamic target engagement following single and multiple dosing, including a food-effect assessment at 75 mg. These results support continued clinical development of SDC-1801 by establishing an initial safety/PK/PD profile and informing dosing conditions.

Brearley C, Francis S, Reader J et al. · British journal of clinical pharmacology · (2026) · View on PubMed ↗

Neuro-immune crosstalk in the tumor microenvironment: mechanisms and therapeutic implications for cancer immunotherapy.

This review examines neuro-immune crosstalk within the tumor microenvironment (TME), focusing on how neural signaling (synapse-like interactions, paracrine neurotransmitter signaling, and electrochemical signaling) shapes immune-cell behavior in cancer. It highlights that neural inputs can promote T-cell exhaustion and expand immunosuppressive populations, contributing to immune evasion and resistance to cancer immunotherapy. The clinical significance is that targeting neural–immune pathways may enhance immunotherapy responsiveness and overcome resistance.

Fan Z, Wang N, Zhang B et al. · Journal of neuroinflammation · (2026) · View on PubMed ↗ · Free PDF ↗

Plasma proteomics reveal SERPINA1 and CD59 as candidate biomarkers for COVID-19 severity stratification and prognosis prediction.

This plasma proteomics study analyzed COVID-19 patients across severity classes to identify proteins associated with severity stratification and prognosis, with validation for mortality and thromboembolic complications. It reported that SERPINA1 and CD59 emerged as candidate biomarkers with predictive utility for COVID-19 severity and longer-term outcomes. The clinical significance is that these proteomic biomarkers may improve risk stratification beyond commonly used markers like D-dimer and fibrin degradation products.

Zhou Z, Liu Q, Ma S et al. · Annals of medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration & dementia (Alzheimer’s, tau, biomarkers, clearance)

Oral GLP-1 receptor agonist promotes astrocyte-neuron lactate and lipid transfer with neuroprotective effects.

The study investigated whether an oral GLP-1 receptor agonist with blood-brain barrier permeability, OHP2, can protect against Alzheimer’s disease by acting on astrocytes and neurons. OHP2 primarily activated GLP-1R on astrocytes to increase aerobic glycolysis and lactate release, which was taken up by neurons to elevate histone H3 lysine 9 lactylation (H3K9la) and promote neuroprotective effects. These findings support a BBB-penetrant oral GLP-1R agonist mechanism linking astrocyte metabolism to neuronal epigenetic regulation as a therapeutic strategy for AD.

Du Y, Sun C, Wu L et al. · Cell metabolism · (2026) · View on PubMed ↗

Lilrb4a Suppression Reprograms Microglia to Mitigate APOE4-Associated Amyloid Plaques and Cerebral Amyloid Angiopathy in Association With a PPAR-Linked Pro-Clearance State.

The study tested whether suppressing the mouse gene Lilrb4a (human LILRB4 ortholog) can mitigate APOE4-associated amyloid pathology in 5xFAD mice carrying human APOE4. Genetic deletion or antisense oligonucleotide knockdown of Lilrb4a reduced cortical amyloid plaque burden and APOE4-associated cerebral amyloid angiopathy without changing Aβ production, and transcriptomics indicated a PPAR-linked pro-clearance microglial state. This identifies Lilrb4a as a potential therapeutic target to reprogram microglia toward amyloid clearance in APOE4-driven Alzheimer’s disease.

Nie C, Yang R, Wang X et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

Clinical Associations of Cerebrospinal Fluid TMEM106B in Familial and Sporadic Frontotemporal Dementia.

This cross-sectional, multicenter clinical study with 2-year follow-up examined cerebrospinal fluid (CSF) TMEM106B levels in two independent frontotemporal dementia (FTD) cohorts, including both familial and sporadic cases. CSF TMEM106B showed clinical associations with features of frontotemporal lobar degeneration/FTD, linking this FTLD susceptibility factor to disease phenotype. These data strengthen TMEM106B as a potential biomarker for clinical stratification and mechanistic understanding of FTLD.

Olzinski M, Downer J, Cobigo Y et al. · JAMA neurology · (2026) · View on PubMed ↗

APOE*4 risk-modifying genes and drug targets in Alzheimer’s disease through cell-type-specific genomic analyses.

This Alzheimer’s & Dementia study performed an APOE4-stratified genome-wide association study (GWAS) of Alzheimer’s disease (N=447,669) and integrated it with brain cell-type-specific multi-omics to identify APOE4 and cell-type-specific genes and enable drug/compound repurposing. The key finding was that APOE4 carriers and non-carriers show distinct sets of cell-type–gene pairs, yielding different candidate risk-modifying genes and drug targets by cell type. This cell-type-aware genetic framework can improve target selection for therapies intended to counteract APOE4–driven AD risk.

Zeng Y, Cook N, Yang C et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗

Choroid plexus remodeling linked to impaired CSF-mediated clearance and Alzheimer’s disease progression.

This study examined how choroid plexus (ChP) remodeling relates to impaired cerebrospinal fluid (CSF)-mediated clearance and Alzheimer’s disease (AD) progression in participants from the ADNI cohort, using structural MRI, amyloid/tau PET, and diffusion tensor imaging (DTI)-derived ALPS measures, with APP/PS1 mice as a complementary model. ChP changes (including increased ChP volume) were linked to worse CSF-mediated clearance proxies and greater AD pathology and cognitive decline across diagnostic stages. These findings suggest ChP remodeling may be a mechanistic contributor to CSF/glymphatic dysfunction that drives AD progression and could become a target for improving clearance pathways.

Yin H, Deng Y, Lu Z et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Blood-based proteomic signature of amyloidosis: identification of novel regulators of amyloid load.

This study mapped plasma proteomic correlates of cerebral amyloidosis by integrating quantitative amyloid PET with large-scale plasma proteomics (SomaScan v4.1; ~7000 proteins) in Aβ-positive individuals from the Knight ADRC and Bio-Hermes cohorts (n=1429). Proteome-wide association analyses identified hundreds of proteins associated with amyloid load and used unsupervised clustering and pathway enrichment to define molecular heterogeneity and novel regulators of amyloid burden among Aβ+ individuals. Clinically, this provides blood-based biomarkers and candidate regulatory pathways that may stratify amyloidosis risk and guide personalized interventions in AD.

Chen Y, Duggan MR, Timsina J et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗

Emerging directions in tauopathy research.

This narrative conference report synthesizes emerging directions in tauopathy research discussed at the Tau Global Conference 2025, covering international progress across tau biology, biomarkers, and therapies. It emphasizes advances in models of tau regulation, degradation, and propagation, alongside improved biomarker development for diagnosis and staging and evolving therapeutic strategies targeting multiple steps of tau pathophysiology. The significance lies in consolidating translational momentum for diagnosing and treating Alzheimer’s and related tau-driven neurodegenerative diseases.

Buée L, Wildsmith KR, Alladi S et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Cell-Specific MicroRNA Networks Orchestrate the Pathogenesis of Alzheimer’s Disease.

This review examined how cell-type-specific microRNA (miRNA) networks in distinct CNS cell populations (neurons, astrocytes, microglia, oligodendrocytes, and less prominently neural stem cells, ependymal cells, and endothelial cells) contribute to Alzheimer’s disease (AD) pathogenesis. It reports that miRNA dysregulation coordinates pathological processes such as amyloid-β (Aβ) plaque formation, hyperphosphorylated tau neurofibrillary tangles, synaptic dysfunction, reactive gliosis, impaired myelin maintenance, reduced neurogenesis, and blood–brain barrier (BBB) dysfunction in a cell-specific manner. These miRNA network insights are significant because they suggest new, cell-targeted regulatory mechanisms and potential miRNA-based therapeutic or biomarker strategies for AD.

Donepudi K, Eadha S, Rodarte D et al. · Ageing research reviews · (2026) · View on PubMed ↗

Mitophagy mitigates tau acetylation via the ULK1-NAD+/SIRT1 axis in Alzheimer’s disease.

This mechanistic study in Alzheimer’s disease (AD) investigated how mitophagy regulates tau acetylation through the ULK1–NAD+/SIRT1 signaling axis. It reports that mitophagy-based metabolic signaling links the autophagy-initiating kinase ULK1 to inhibition of pathogenic tau acetylation via NAD+/SIRT1, with human biofluid-to-postmortem and transcriptomic analyses showing age-associated decline of ULK1. Scientifically, the findings identify a ULK1–NAD+/SIRT1 mitophagy pathway as a potential early intervention target to restrain tau pathology in AD.

Pan JP, Zhang J, Wang PJ et al. · Autophagy · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurobiology & brain circuits (TBI, BBB, myelin, connectomics, organoids)

Mitochondrial DNA heteroplasmy drives cortical neuronal disturbances in human organoids harbouring the common m.3243A>G mutation.

This work studied how mitochondrial DNA (mtDNA) heteroplasmy affects cortical function using human iPSC-derived cerebral organoid slice models carrying the common m.3243A>G mutation in MT-TL1 (mt-tRNALeu). The organoid model recapitulated cortical architecture and mitochondrial pathology, and single-cell approaches were used to link heteroplasmy levels to neuronal disturbances. The study provides a human, mutation-specific platform for dissecting MELAS (m.3243A>G) neurobiology and for informing future therapeutic strategies.

Hathazi D, Lyons C, Lagos D et al. · Nature communications · (2026) · View on PubMed ↗

Direct evidence of upper motor neuron excitability changes in a patient with ALS.

This case study directly measured corticospinal output evoked by transcranial magnetic stimulation (TMS) in a patient with amyotrophic lateral sclerosis (ALS) to assess upper motor neuron excitability changes. By recording upstream of spinal circuitry, the authors provided direct evidence of altered excitability that addresses limitations of prior TMS studies that relied on muscle responses. The findings strengthen human mechanistic understanding of ALS hyperexcitability and improve interpretation of noninvasive neurophysiology biomarkers.

Di Lazzaro V, Pellegrino G, Corp DT et al. · Journal of neurophysiology · (2026) · View on PubMed ↗ · Free PDF ↗

Human BBB-brain organoid on a millifluidic plate for modeling brain parenchymal pathology-induced barrier dysfunction.

This engineering study developed a human blood–brain barrier–brain organoid-on-a-chip (BBOC) model using human brain microvascular endothelial cells on a millifluidic plate to model BBB dysfunction driven by brain parenchymal pathology. It demonstrated an integrated BBB–parenchyma platform that enables physiological interaction and pathological disruption of barrier function in a more realistic way than conventional BBB-only models. The significance is that this millifluidic BBOC can improve mechanistic studies of BBB–parenchyma crosstalk and better support drug evaluation for barrier penetration and neural targeting.

Zhu L, Zhao W, Shen M et al. · Journal of advanced research · (2026) · View on PubMed ↗ · Free PDF ↗

EGR1 mediates neuronal damage via suppressing HIF1A-induced mitophagy following traumatic brain injury.

This study examined how the transcription factor EGR1 mediates neuronal damage after traumatic brain injury (TBI) by suppressing HIF1A-induced mitophagy via the HIF1A–BNIP3 axis. Integrated transcriptomic and epigenomic analyses identified EGR1 as acutely upregulated in injured neurons, and genetic ablation of Egr1 in mice reduced neuronal apoptosis and preserved dendritic integrity. The results suggest that targeting EGR1 could restore HIF1A-driven mitophagy and mitigate neurodegeneration following TBI.

Hou X, Zhang D, Sang X et al. · Autophagy · (2026) · View on PubMed ↗

Near-Infrared and Red-Light Photobiomodulation for Ocular Aging and Diseases: A Narrative Review.

This narrative review synthesized evidence for near-infrared (NIR) and red-light photobiomodulation (PBM) as non-invasive therapies for ocular aging and eye diseases, emphasizing mitochondrial dysfunction, oxidative stress, and inflammation as key mechanisms. It provides an evidence-weighted, indication-specific synthesis of PBM applications across ophthalmic conditions. The clinical significance is to guide ophthalmology practice by clarifying where PBM may serve as an adjunctive mitochondrial-targeted treatment.

Waisberg E, Ong J, Yaldo L et al. · Ophthalmology and therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Oligodendrocyte Piezo2 is a regulator of age-dependent myelin integrity and dysregulated in multiple sclerosis.

This study examined the role of the mechanosensitive ion channel Piezo2 in oligodendrocytes (OLs) and its relevance to age-dependent myelin integrity and multiple sclerosis (MS). Using single-nucleus RNA sequencing, it identified Piezo2 expression in late differentiated OLs in the murine optic nerve, and OL-specific Piezo2 deficiency caused age-dependent motor impairment and selective disruption of myelin compaction in vulnerable small-caliber optic nerve axons. The findings position oligodendrocyte Piezo2 as a regulator of myelin maintenance and a potential contributor to MS-associated demyelination.

Dyckow-Schubart J, Rabitsch AM, Geywitz C et al. · Communications biology · (2026) · View on PubMed ↗ · Free PDF ↗

A synaptoid connectome differentiates tanycytic subpopulations and underlies neuroglial communication and neuroendocrine regulation.

The study mapped a synaptoid (synapse-like) connectome to define tanycytic subpopulations and their roles in neuroglial communication and neuroendocrine regulation in mice. It showed that neuron–tanycyte synaptoids are abundant and synapse-like, that tanycyte subtypes receive distinct hypothalamic and extrahypothalamic inputs and respond to multiple neurotransmitters/neuromodulators, and it provided proof-of-function using kisspeptin-related neuroendocrine regulation. These results establish a circuit-level framework for how tanycytes integrate neural signals to control neuroendocrine and metabolic outputs.

Neve V, Fernandois D, Rai S et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiometabolic risk & biomarkers (diabetes, CKM, IR, inflammation indices)

Timing of Antidiabetic Medication Initiation and Risk of Cardiovascular Events and Mortality.

This cohort study in adults newly meeting diagnostic criteria for type 2 diabetes (T2D) in Korea (2013–2022) used target trial emulation with a clone-censor-weight approach to assess whether antidiabetic medication (ADM) initiation within 3, 6, or 12 months was associated with major adverse cardiovascular events (MACE) and all-cause mortality. Earlier ADM initiation was associated with lower risk of MACE and death compared with later initiation. The results support timely treatment initiation after T2D diagnosis to reduce long-term cardiovascular harm.

Ko HY, Shin JY, Jung K et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Optimizing early triage for subclinical cardiovascular-kidney-metabolic syndrome: longitudinal associations, incremental value, and clinical utility of nine insulin resistance surrogates.

This longitudinal cohort study in 2,958 Chinese adults at cardiovascular-kidney-metabolic (CKM) stages 0–2 compared nine non-insulin-based insulin resistance surrogate indices for predicting progression to CKM stage 3. Several surrogate indices showed incremental predictive value for future CKM stage 3, supporting scenario-specific risk stratification beyond baseline clinical factors. Scientifically and clinically, identifying the best insulin-resistance surrogates could improve early triage for subclinical target-organ damage and guide monitoring or preventive interventions.

Huang Y, Qu X, Xu S et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Burden trajectories of stroke attributable to lipid-glucose dysfunction and biomarker validation: evidence from the global burden of disease (GBD) 2023 and the China health and retirement longitudinal study (CHARLS).

This study assessed temporal trends in stroke burden attributable to high fasting plasma glucose (FPG) and high low-density lipoprotein cholesterol (LDL-C) using Global Burden of Disease (GBD) 2023 estimates in China and evaluated the predictive performance of lipid-glucose metabolic biomarkers for incident stroke in the China Health and Retirement Longitudinal Study (CHARLS). It found that lipid-glucose dysfunction metrics (high FPG and high LDL-C) contribute to stroke burden over time and that specific lipid-glucose biomarkers have measurable prognostic value for future stroke risk at the individual level. These findings are clinically significant because they support biomarker-based risk stratification and prevention strategies for stroke in China’s aging population.

Xiao Z, Deng L, Duan Y et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Associations of insulin resistance-related indices with the risk and progression of cardiometabolic multimorbidity in individuals with metabolic dysfunction-associated steatotic liver disease: a prospective cohort study.

This prospective cohort study evaluated associations between insulin resistance (IR)-related indices and the risk and progression of cardiometabolic multimorbidity (CMM) in 109,604 UK Biobank participants with metabolic dysfunction-associated steatotic liver disease (MASLD). It reports that multiple IR metrics—including the triglyceride–glucose (TyG) index and TyG-derived variants—are associated with higher risk of developing CMM and with stage-specific disease progression among people with MASLD. The significance is that IR-related, routinely measurable indices could improve prediction and stratification of cardiometabolic complications in MASLD.

Sun M, He Q, Wang Y et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Association of noninvasive liver fibrosis scores with severity and outcomes among individuals with cardiovascular-kidney-metabolic syndrome: evidence from the NHANES 2005-2018.

This retrospective cohort analysis used NHANES 2005–2018 data (n=8,592) to test whether noninvasive liver fibrosis scores relate to cardiovascular-kidney-metabolic (CKM) syndrome severity and clinical outcomes. It evaluated six fibrosis scores—LiverRisk, MAF-5, NFS, FIB-4, SAFE, and APRI—and found that higher fibrosis-score levels were associated with greater CKM syndrome severity and worse outcomes. The clinical significance is that liver fibrosis scores may serve as practical risk markers for CKM syndrome progression in population settings.

Gao Y, Chen H, Li J et al. · BMC cardiovascular disorders · (2026) · View on PubMed ↗ · Free PDF ↗

Cumulative visceral fat burden and progression to advanced cardiovascular kidney metabolic syndrome in Chinese middle-aged and older adults.

This longitudinal cohort study in 3,322 Chinese middle-aged and older adults examined whether baseline visceral fat burden (METS-VF) and cumulative metabolic exposure (cumMETS-VF) predict progression to advanced cardiovascular-kidney-metabolic (CKM) syndrome. Higher baseline METS-VF and higher cumMETS-VF were associated with increased risk of advancing to advanced CKM syndrome over repeated metabolic assessments in CHARLS. The findings support using METS-VF and cumulative METS-VF as practical risk stratification tools for identifying people likely to develop severe CKM disease.

Fang Z, Xue A, Liu Q et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

Contrastive Machine Learning to Quantify Hypertensive Multiorgan Damage and Identify New Disease Phenotypes: A Multinational Multimodal Study.

This multinational, multimodal study used contrastive machine learning to quantify hypertension-associated multiorgan damage and infer disease progression trajectories in 27,099 participants from the UK Biobank imaging substudy. It developed a semisupervised contrastive trajectory inference (cTI) framework that mapped progression from health to advanced disease in a pseudotemporal manner and identified organ-specific progression patterns and new disease phenotypes. The scientific and clinical significance is that this approach can improve subclinical risk detection and prediction of organ-specific deterioration in hypertensive patients.

Alkhodari M, Lapidaire W, Kart T et al. · Circulation · (2026) · View on PubMed ↗

Proteomics of multimorbidity progression across cardiometabolic diseases and cancer in a multinational cohort.

This multinational cohort study used large-scale plasma proteomics (SomaScan 7k; 7,289 aptamers) to identify protein signatures underlying multimorbidity progression across cardiovascular disease (CVD), type 2 diabetes (T2D), and cancer in 13,270 EPIC participants. It modeled multimorbidity as sequential disease transitions from baseline disease-free status to a first disease and then to a second disease. Scientifically, the proteomic transition signatures may reveal shared biological mechanisms and candidate targets for interventions aimed at preventing or slowing multimorbidity progression.

Stein MJ, Viallon V, Leitzmann MF et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Associations between the C-reactive protein-triglyceride-glucose index and its derived indices and the incidence and progression of cardiometabolic multimorbidity in participants with metabolic dysfunction-associated steatotic liver disease: a large-scale prospective cohort study.

This large-scale prospective cohort study evaluated whether the C-reactive protein–triglyceride–glucose index (CTI) and obesity-related derived indices predict incidence and progression of cardiometabolic multimorbidity (CMM) in 109,181 UK Biobank participants with metabolic dysfunction–associated steatotic liver disease (MASLD). Higher CTI-related exposure was associated with greater risk of developing and worsening CMM, with obesity-related derivative indices providing incremental predictive value and suggesting potential biomarker roles. These findings support CTI-based risk stratification for cardiometabolic disease trajectories in MASLD and may help identify patients who need earlier preventive interventions.

Tian Z, Yan X, Xue F et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Cumulative exposure and longitudinal exposure pattern of C-reactive protein-triglyceride-glucose index combined with Chinese visceral adiposity index (CTI-CVAI) and the risk of new-onset cardiovascular disease in middle-aged and older Chinese adults: a prospective cohort study based on the China Health and Retirement Longitudinal Survey (CHARLS).

This prospective cohort study in middle-aged and older Chinese adults from the China Health and Retirement Longitudinal Survey (CHARLS) assessed cumulative exposure and longitudinal patterns of the C-reactive protein–triglyceride–glucose index combined with the Chinese visceral adiposity index (CTI-CVAI) for new-onset cardiovascular disease (CVD), heart disease, and stroke. The study found that higher cumulative CTI-CVAI exposure and adverse longitudinal trajectories were associated with increased risk of incident CVD outcomes. These data suggest that combining inflammation/insulin-resistance (CTI) with visceral adiposity (CVAI) improves cardiovascular risk prediction in aging populations.

Chen X, Wang C, Luo Y et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular therapeutics & mechanisms (heart injury, MR antagonism, HCM pathways)

NUAK1 Inhibition Alleviates Ischemia-Reperfusion Injury via SYNE1-YAP1.

This study investigated whether NUAK1 (AMPK-related kinase 5) inhibition protects the heart from ischemia-reperfusion injury by regulating mechanosensitive nuclear signaling through SYNE1 (nesprin-1)/YAP1 during hypoxia/reoxygenation and ischemia-reperfusion. Using quantitative phosphoproteomics, coimmunoprecipitation, and in vitro kinase assays, the authors found NUAK1 directly phosphorylates SYNE1 (Nesprin1-α2/SYNE1) at a conserved site (S434; S8284 in nesprin-1 giant), and NUAK1 inhibition alleviated injury via the SYNE1–YAP1 axis. Scientifically, this identifies a NUAK1→SYNE1→YAP1 signaling mechanism and suggests NUAK1 as a potential therapeutic target to reduce myocardial ischemia-reperfusion damage.

Bai Y, Zhao T, Wang Q et al. · Circulation research · (2026) · View on PubMed ↗

Mitochondrial-derived peptide MOTS-c activates metabolic signaling but blunts reparative function in human mesenchymal stromal cells.

This study tested the mitochondria-derived peptide MOTS-c in human adipose-derived mesenchymal stromal cells (MSCs) isolated from obese patients (BMI ≥ 30 kg/m2) versus lean donors (BMI < 30 kg/m2). MOTS-c activated metabolic signaling pathways but reduced reparative function in these human MSCs, indicating a dissociation between metabolic activation and therapeutic capacity. Clinically, this implies that MOTS-c–based metabolic modulation may not reliably restore MSC reparative efficacy in obesity and warrants caution and further mechanistic optimization for MSC therapies.

Xing L, Lu B, Zhu X et al. · Inflammation and regeneration · (2026) · View on PubMed ↗ · Free PDF ↗

Panax quinquefolium saponin decreases atherosclerosis in ovariectomized ApoE-/- mice via regulating estrogen receptor α.

This preclinical study evaluated Panax quinquefolium saponin (PQS) in ovariectomized ApoE-/- mice, modeling postmenopausal atherogenesis at 8 or 14 weeks. PQS reduced atherosclerotic plaque burden and modulated estrogen receptor α–related signaling, alongside changes in serum inflammatory cytokines and endothelial apoptosis in vivo and oxidative injury responses in HUVECs. These results support estrogen receptor α as a mechanistic target for PQS in postmenopausal atherosclerosis and justify further translational investigation.

Chen L, Shi JH, Ma XJ et al. · Chinese medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Therapeutic potential of ELABELA in alleviating hereditary hypertrophic cardiomyopathy.

This study examined ELABELA (ELA) and its apelin receptor (APJ) signaling in hereditary hypertrophic cardiomyopathy (HCM) by analyzing myocardial tissues from HCM patients and using sarcomere mutation models. It found dysregulated ELA/APJ signaling in hereditary HCM and showed that restoring ELA signaling had therapeutic effects that improved disease-relevant cardiac phenotypes. The clinical significance is that ELA/APJ pathway modulation may represent a potential treatment strategy for hereditary HCM, potentially addressing limitations of existing therapies such as mavacamten.

Ye C, Xu T, Yang H et al. · Journal of advanced research · (2026) · View on PubMed ↗ · Free PDF ↗

Finerenone mitigates acute alcoholic myocardial injury by modulating inflammatory signaling, oxidative stress, and mitochondrial function.

This preclinical study tested whether finerenone, a next-generation non-steroidal mineralocorticoid receptor (MR) antagonist, mitigates acute alcoholic myocardial injury in in vitro and in vivo models of acute alcoholic cardiotoxicity. Finerenone reduced inflammatory signaling, oxidative stress, and mitochondrial dysfunction, thereby improving acute myocardial injury phenotypes. The findings support targeting the aldosterone/MR axis with finerenone as a potential therapeutic strategy for alcoholic cardiomyopathy and related acute myocardial damage.

Liu CH, Chu TH, Yang SM et al. · Molecular medicine (Cambridge, Mass.) · (2026) · View on PubMed ↗ · Free PDF ↗

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Respiratory disease & ventilation/biomarkers (ARDS, COPD, asthma, TB)

Exhaled Nitric Oxide Predicts Glucocorticoid Response in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

This retrospective clinical study evaluated whether fractional exhaled nitric oxide (FeNO) predicts glucocorticoid response during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Patients with FeNO ≥25 ppb at admission (high FeNO, n=61) were compared with those below this threshold (low FeNO, n=61), with all receiving standard therapy and the subgroup receiving additional systemic glucocorticoids. If validated, FeNO could be used to stratify AECOPD patients likely to benefit from systemic glucocorticoids.

Chen J, Li J, Wang W et al. · Journal of visualized experiments : JoVE · (2026) · View on PubMed ↗

PEEP and alveolar recruitment after 60 years of acute respiratory distress syndrome.

This narrative/clinical review focused on how positive end-expiratory pressure (PEEP) and alveolar recruitment behave in acute respiratory distress syndrome (ARDS) over the last 60 years, emphasizing patient-specific differences in recruitability. The key finding is that PEEP’s net benefit depends on a balance between recruitment (lung protection) and overdistension/stress in poorly recruitable regions (potential harm). Clinically, this supports more individualized PEEP strategies rather than one-size-fits-all settings to minimize ventilator-induced lung injury.

Grieco DL, Coudroy R, Jonkman AH et al. · Intensive care medicine · (2026) · View on PubMed ↗

Upregulation of LncRNA MIR31HG in COPD Correlates with Disease Severity and Facilitates Inflammation via miR-342-3p.

This COPD study measured serum lncRNA MIR31HG and miR-342-3p by RT-qPCR in healthy controls, stable COPD patients, and acute exacerbation COPD (AECOPD) patients, and used an in vitro COPD-like model to test function. MIR31HG was upregulated in COPD, correlated with disease severity, and promoted inflammation through a miR-342-3p–dependent mechanism. These findings suggest the MIR31HG/miR-342-3p axis as a potential biomarker and therapeutic target for COPD progression.

Zhao J, Zhang Y, Gao L et al. · COPD · (2026) · View on PubMed ↗ · Free PDF ↗

Causal Relationship Between Methotrexate and Chronic Obstructive Pulmonary Disease: A Study Based on Network Toxicology and Mendelian Randomization.

This study combined network toxicology with Mendelian randomization (MR) to evaluate whether methotrexate (MTX) has a causal relationship with chronic obstructive pulmonary disease (COPD) risk. The analysis aimed to infer causality by linking MTX-related targets/pathways from network toxicology to genetic instruments in MR. If supported by the MR results, the findings would clarify whether MTX use could causally influence COPD development and inform repurposing decisions.

Xiang YX, Zou FS, Shi MF et al. · International journal of chronic obstructive pulmonary disease · (2026) · View on PubMed ↗ · Free PDF ↗

Adhesion molecules and T cell imbalance in severe eosinophilic asthma: Insights from anti-IL-5R treatment.

This study characterized adhesion molecule expression (ICAM-1, ICAM-3, and L-selectin/CD62L) on T-cell subsets in severe eosinophilic asthma (SEA) patients and tested how IL-25 and IL-33 modulate these markers, including assessment of immunologic effects of benralizumab therapy. The key finding was that SEA is associated with T-cell adhesion molecule imbalance and that anti–IL-5R treatment (benralizumab) can remodulate these adhesion-related immune trafficking signals. This is significant because it links biologic therapy to mechanistic changes in immune cell trafficking/activation pathways that may contribute to SEA control.

Bergantini L, Paggi I, Pianigiani T et al. · Pulmonology · (2026) · View on PubMed ↗ · Free PDF ↗

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Microbiome, gut–lung axis & intestinal inflammation

Inhibition of Aryl hydrocarbon receptor Interleukin-22 signaling and worsening of intestinal inflammation by Sutterella species.

This study tested whether Sutterella species worsen intestinal inflammation by inhibiting aryl hydrocarbon receptor (AhR)–interleukin-22 (IL-22) signaling. The key finding was that Sutterella-driven disruption of the AhR–IL-22 pathway impaired protective mucosal immune responses and exacerbated intestinal inflammatory phenotypes. This is significant because it identifies a specific host–microbe immune axis (AhR/IL-22) that could be leveraged for therapeutic strategies in inflammatory bowel disease.

Dupraz L, Orianne G, Da Costa G et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

Cross-kingdom microbiome interactions along the gut-lung axis: immune-microecological coordination, shared mechanisms, and disease-context dependence in respiratory disorders.

This review synthesized evidence on cross-kingdom microbiome interactions along the gut-lung axis and how immune–microecological coordination contributes to respiratory disorders. It concluded that bacteria, fungi, and bacteriophages can influence susceptibility, inflammatory tone, and treatment responsiveness through shared but context-dependent mechanisms across diseases such as asthma, COPD, ARDS, and lung cancer. The significance is that it frames the gut-lung microbiome as a multi-kingdom, mechanism-linked determinant of respiratory disease biology and therapeutic outcomes.

Yu J, Meng J, Shi Z et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

Biofilm overproduction enhances gastrointestinal stress tolerance and intestinal fitness in Bacillus subtilis.

This study examined whether biofilm phenotypes in Bacillus subtilis—using a biofilm-deficient tasA eps mutant, a biofilm-overproducing sinR mutant, and an isogenic wild-type control—improve survival under gastrointestinal stresses. The biofilm-overproducing strain showed enhanced tolerance to simulated gastric and bile stresses and improved intestinal fitness compared with biofilm-deficient and wild-type strains. These findings suggest that engineering biofilm regulatory pathways (e.g., sinR) could be a practical strategy to improve the robustness and functional delivery of probiotic or therapeutic Bacillus strains through the GI tract.

Kunyeit L, Rao R · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

Clinical features and therapeutic requirements of perianal disease in adult patients with ulcerative colitis: the PERICO study of the ENEIDA registry.

This retrospective ENEIDA registry analysis studied the prevalence, clinical course, and treatment needs of perianal disease (PD) among 9,884 adults with ulcerative colitis (UC). PD occurred in 411 patients (incidence 0.5 per 100 person-years), and 22% developed PD before UC diagnosis, indicating frequent diagnostic delay and a distinct clinical phenotype. Characterizing PD burden and therapeutic requirements in UC can improve risk stratification and guide earlier, more targeted management strategies for adult patients with UC-associated PD.

Guasch M, Calafat M, Gargallo-Puyuelo CJ et al. · Inflammatory bowel diseases · (2026) · View on PubMed ↗

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Infectious disease & parasitology (malaria, toxoplasma, TB models)

Genome-wide CRISPR screen identifies ELFN2 as a key regulator of host autophagy and lipid metabolism important for Toxoplasma gondii proliferation.

This Autophagy study used a genome-wide CRISPR knockout screen in the porcine PK15 cell line to identify host regulators of Toxoplasma gondii replication, focusing on the host gene ELFN2. Disrupting ELFN2 reduced T. gondii proliferation without impairing PK15 cell growth, and ELFN2 loss decreased host macroautophagy/autophagy and impaired lipid metabolism required for parasite growth. The work identifies ELFN2 as a host dependency factor that could be exploited to limit toxoplasmosis by targeting host autophagy/lipid pathways.

Xu H, Liu H, Lu T et al. · Autophagy · (2026) · View on PubMed ↗

Disease progression is associated with differential neutrophil maturation in Mycobacterium tuberculosis-infected macaques.

This study investigated how Mycobacterium tuberculosis (Mtb) infection affects neutrophil maturation and relates to disease progression outcomes in infected macaques. It found that differential neutrophil maturation patterns were associated with progression states, linking innate immune cell phenotypes to infection trajectory. The significance is that neutrophil maturation dynamics may help explain protective versus harmful innate responses in TB and could guide future immunomodulatory strategies.

Dinko S, Joly C, Mazet P et al. · Journal of immunology (Baltimore, Md. : 1950) · (2026) · View on PubMed ↗ · Free PDF ↗

A role for the poly-asparagine repeat in the Plasmodium histone acetyltransferase, PfGCN5.

This study examined the function of the poly-asparagine repeat in the Plasmodium falciparum histone acetyltransferase PfGCN5. The poly-asparagine-containing N-terminus associates with the PfGCN5 catalytic domain after nuclear cleavage, and deleting the repeat destabilized the N-terminus, impairing parasite development and growth—especially under stress—using high-resolution mass spectrometry and related approaches. The results reveal a repeat-dependent mechanism controlling PfGCN5 stability and parasite fitness, highlighting a potential vulnerability in malaria biology.

Rubiano K, Morris A, Vitorino FDL et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Inflammation, stress biology & innate immunity (cGAS–STING, MAM, autophagy, proteostasis)

Heat stress reveals bidirectional cross talk between the heat shock response and UPRER in C. elegans.

This study in the nematode C. elegans examined how heat stress bidirectionally cross-talks between the heat shock response and UPRER (unfolded protein response in the endoplasmic reticulum). The authors found that heat stress activates both programs and that UPRER signaling can, in turn, influence the heat shock response, indicating coordinated regulation rather than independent stress pathways. This is significant for understanding how organisms integrate multiple proteostasis and stress inputs to maintain cellular homeostasis.

Alcala A, Castro Torres T, Aviles Barahona R et al. · G3 (Bethesda, Md.) · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochondria-associated endoplasmic reticulum membrane (MAM): roles in innate immunity dysregulation.

This article reviews how mitochondria-associated endoplasmic reticulum membrane (MAM) signaling coordinates innate immune responses by regulating calcium homeostasis, lipid metabolism, mitochondrial dynamics, mitochondrial protein modifications, and autophagy in cells. It highlights that MAM-driven calcium control influences mitochondrial energy metabolism and inflammasome activation, while MAM-regulated mitochondrial fission/fusion is linked to mitochondrial DNA (mtDNA) release that can trigger innate immune signaling. Understanding MAM as a hub for inflammasome and antiviral pathway regulation is significant because it identifies mechanistic targets for modulating dysregulated innate immunity in disease.

Zhang Q, Gao J, Yang Y et al. · Cell communication and signaling : CCS · (2026) · View on PubMed ↗ · Free PDF ↗

Melatonin-treated bone marrow mesenchymal stem cell-derived exosomes reverse liver fibrosis induced by CCl4 in male wistar albino rats.

The study tested whether melatonin-pretreated bone marrow mesenchymal stem cell-derived exosomes (MT/Exos) could mitigate carbon tetrachloride (CCl4)-induced liver fibrosis in male Wistar albino rats. MT/Exos were characterized by protein content, particle size, and CD marker expression, and were administered via caudal vein injection (100 µg/rat twice weekly for 4 weeks) with effects assessed using liver biomarkers, oxidative stress, inflammatory and fibrotic cytokines, apoptosis markers, and histopathology. This preclinical exosome-based strategy suggests melatonin priming may enhance therapeutic efficacy against MASH/CCl4-type fibrotic remodeling by targeting multiple fibrosis-driving pathways.

Abdelbaky NW, Nabil A, Ahmed OM et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

Therapeutic targeting of AREL1 in hepatic stellate cells attenuates MASH-related liver fibrosis.

The study investigated therapeutic targeting of the gene AREL1 (Arel1) in hepatic stellate cells (HSCs) to attenuate metabolic-associated steatohepatitis (MASH)-related liver fibrosis in male mice. Integrated single-cell and single-nucleus RNA-seq analyses of human healthy and fibrosis samples identified an HSC subpopulation in MASH with uniquely upregulated AREL1, and HSC-specific Arel1 knockout markedly reduced fibrosis in MASH model mice. These results position AREL1 as a mechanistically relevant HSC activation driver and a potential therapeutic target for MASH-associated fibrogenesis.

Zhang YW, Pan X, Zhang M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Activation of microglial PPARγ by asperosaponin VI alleviates stress-induced depression and synaptic impairment.

This preclinical study screened and evaluated natural peroxisome proliferator-activated receptor gamma (PPARγ) agonists for their ability to activate microglial PPARγ and tested antidepressant effects in stress-induced depression models. It identified asperosaponin VI as a microglia-targeting PPARγ activator that alleviated stress-induced depressive-like behavior and reduced synaptic impairment. Scientifically, targeting microglial PPARγ with asperosaponin VI is significant because it provides a brain-microglia-directed mechanism for improving depression-associated synaptic dysfunction.

Ge Y, Yang C, Wang M et al. · Journal of advanced research · (2026) · View on PubMed ↗ · Free PDF ↗

Eosinophil-derived apoptotic extracellular vesicles accelerate steatotic liver repair after ischemia/reperfusion injury through mitochondria-associated metabolic reprogramming.

This study investigated whether eosinophil-derived apoptotic extracellular vesicles (Eos-ApoEVs) accelerate steatotic liver repair after ischemia/reperfusion (I/R) injury and defined underlying mechanisms. Eos-ApoEV treatment reversed oxygen-glucose deprivation/reperfusion (OGD/R)-induced dysfunction in hepatocytes and liver sinusoidal endothelial cells and promoted steatotic repair through mitochondria-associated metabolic reprogramming. The work supports eosinophil-derived ApoEVs as a cell-free therapeutic strategy for steatotic liver I/R injury by targeting mitochondrial metabolic pathways.

Xiong C, Chen L, Rao Z et al. · Journal of nanobiotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

Lactylation: a novel post-translational modification for cGAS-STING pathway.

This review article synthesized current evidence on lysine lactylation (lactylation; Kla), a lactate-derived post-translational modification, as a regulator of the cGAS–STING innate immune signaling pathway. It summarizes molecular mechanisms by which lactylation can modulate cGAS–STING activation and downstream inflammatory responses, linking cellular metabolic state to antiviral and antitumor immunity. The review provides a mechanistic framework that may guide future therapeutic targeting of metabolic-epigenetic control of cGAS–STING signaling.

Wang H, Wang Z, Meng F et al. · Inflammation research : official journal of the European Histamine Research Society … [et al.] · (2026) · View on PubMed ↗

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Metabolic–epigenetic regulation & post-translational modifications (lactylation, glycosylation, chromatin)

Sensing centrosome amplification: the interface between centriole duplication and autophagy.

This study used a genome-wide screen in mouse embryonic stem cells to identify pathways that allow cells to bypass proliferation arrest caused by PLK4-mediated centrosome amplification. Downregulation of Wnt, Hippo, Tpr53, PIDDosome, ciliary biogenesis, or autophagy pathways enabled proliferation under centrosome amplification, and depletion of the tumor suppressor ARHGAP15 promoted autophagy and overcame the amplification block. The work clarifies how autophagy interfaces with centrosome duplication control, offering mechanistic insight into how cancer-like centrosome amplification can be tolerated.

Coelho PA, Fatalska A, Geymonat M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

SPOP-mediated nuclear ubiquitination degradation of p62/SQSTM1 contributes to HR repair.

This mechanistic cancer biology study investigated how SPOP mediates nuclear ubiquitination and degradation of p62/SQSTM1 to promote homologous recombination (HR) repair. It found that DNA damage enhances nuclear interaction between SPOP and p62/SQSTM1, leading to SPOP-dependent ubiquitination of p62/SQSTM1 at lysine 7, its degradation, increased RAD51 and FLNA expression, RAD51 foci formation, and higher HR efficiency. The work also links patient-derived SPOP-binding motif mutations (S276Y/S277G/S277I) to altered radiotherapy responses, suggesting a potential biomarker axis for DNA damage–based treatment.

Yang X, Zhou Y, Huang Q et al. · Oncogene · (2026) · View on PubMed ↗ · Free PDF ↗

Psc and Su(z)2 safeguard intestinal stem cell identity and prevent chinmo-dependent tumorigenesis.

The study examined how simultaneous loss of the Polycomb repressive complex 1 (PRC1) component Psc and its homolog Su(z)2 in adult Drosophila intestinal stem cells (ISCs) affects tumorigenesis and lineage signaling. Loss of Psc and Su(z)2 caused tumors of proliferative, undifferentiated cells while failing to activate key ISC proliferation/differentiation pathways including JAK/STAT, Ras/MAPK, Wnt, and Notch/JAK/STAT. These findings identify PRC1-mediated epigenetic safeguards as essential for maintaining ISC identity and preventing chinmo-dependent tumor development in vivo.

Wei R, Yu H, Sun Q et al. · EMBO reports · (2026) · View on PubMed ↗ · Free PDF ↗

Role of CHD chromatin remodelers in heart development.

This narrative review synthesized evidence on the nine CHD (chromodomain helicase DNA-binding) ATP-dependent chromatin remodelers and their stage-specific roles in heart development. Genetic and functional studies link CHD-family mutations to congenital heart disease, arrhythmias, and cardiomyopathies, but the review highlights that contributions of individual CHD members across developmental stages and maturation remain incompletely defined. Scientifically, clarifying CHD-specific developmental windows and mechanisms could improve interpretation of CHD-related congenital cardiac phenotypes and guide future functional studies.

Sun SY, Feng ZY, Sheng W et al. · World journal of pediatrics : WJP · (2026) · View on PubMed ↗ · Free PDF ↗

RNA binding motif protein RBM41 promotes colorectal tumorigenesis by impeding the maturation of NDRG1 pre-mRNA.

This study investigated whether RNA-binding motif protein RBM41 promotes colorectal tumorigenesis by blocking maturation of NDRG1 pre-mRNA in colorectal cancer (CRC). RBM41 was elevated in CRC and associated with poor prognosis; RBM41 overexpression increased malignant proliferation, while RBM41 inhibition reduced proliferation and induced autophagic cell death and apoptosis in HT29 and SW480 cells. Mechanistically, RBM41 impeded NDRG1 pre-mRNA processing, suggesting an RBM41–NDRG1 axis as a potential therapeutic target in CRC.

Liu Y, Mu J, Yu J et al. · Cell death discovery · (2026) · View on PubMed ↗ · Free PDF ↗

Structural basis of nonmuscle myosin-2 autoinhibition mechanisms.

The study determined structural mechanisms of nonmuscle myosin-2 (NM2) autoinhibition by resolving features of the elongated full-length 10S (autoinhibited) conformation. It reports structural insights into how the monomeric 10S state suppresses ATPase activity, actin binding, and filament assembly relative to the active filamentous state. These structural principles advance understanding of how NM2 contractility is spatially and temporally controlled in cells.

Heissler SM, Grandinetti G, Sellers JR et al. · Nature communications · (2026) · View on PubMed ↗

Choline metabolism drives metastasis in BRCA1-deficient ovarian cancers by activating FAM3C.

The study investigated how choline metabolism drives metastasis in BRCA1-deficient ovarian cancer through activation of FAM3C. Using metabolomics, it found that BRCA1 deficiency increases choline metabolism by upregulating the choline transporter-like protein CTL4, with BRCA1 recruiting EZH2 to deposit H3K27Me3 at the CTL4 promoter, leading to CTL4 overexpression in BRCA1-mutant tumors. This links BRCA1 loss to a specific metabolic–epigenetic program that promotes metastatic behavior via FAM3C signaling, suggesting actionable metabolic targets.

Wang C, Xie X, Li J et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Lifestyle, psychosocial factors & rehabilitation (exercise, loneliness, diet, PBM, trials)

Biological aging and generational shifts in early-onset cancer risk.

This analysis studied whether systemic biological aging differs across birth cohorts and whether it predicts early-onset cancer risk in 154,169 young adults from the UK Biobank. Systemic aging measured by PhenoAge increased across cohorts and was associated with higher early-onset solid cancer risk (HR per SD 1.08, 95% CI 1.03–1.13), with effects driven by sites including lung and gastrointestinal cancers. The findings support biological aging as an integrative risk marker for generational increases in early-onset cancer and motivate interventions that reduce aging-related risk.

Tian R, Zong X, Ren D et al. · Nature medicine · (2026) · View on PubMed ↗

Role of an Ayurvedic formulation ‘Kalyanaka Ghrita’ in Mild Cognitive Impairment: A single-patient, quasi-randomized, controlled, open-label N-of-1 trial.

This single-patient, quasi-randomized, controlled N-of-1 trial evaluated the Ayurvedic polyherbal formulation Kalyanaka Ghrita (KG) for efficacy and safety in a patient diagnosed with mild cognitive impairment (MCI). The study assessed KG’s effects using an N-of-1 design aligned with individualized Ayurveda decision-making, aiming to determine whether KG improves cognitive outcomes while monitoring tolerability. If effective in this individualized setting, KG would provide a proof-of-concept for using N-of-1 trials to systematically evaluate traditional formulations for MCI.

Sharma S, Kaushik A, Chakrabarti SS et al. · Journal of ethnopharmacology · (2026) · View on PubMed ↗

Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar depression: A systematic review and dose-related network meta-analysis across different age groups.

This systematic review and dose-related network meta-analysis studied comparative efficacy, response, and acceptability of pharmacological treatments for acute bipolar depression across different age groups, using randomized controlled trials indexed in major databases up to 2025-11-25. It synthesized dose effects on depressive symptom change, response, and tolerability/acceptability across treatments and placebo. Clinically, the results aim to guide age-specific medication selection for acute bipolar depression by identifying which drug classes and dose ranges perform best on both efficacy and tolerability.

Fornaro M, Di Lorenzo C, Oliva V et al. · Journal of affective disorders · (2026) · View on PubMed ↗

Loneliness, unhealthy lifestyle, and incident cardiometabolic disease among middle-aged and older adults across 33 countries: a multicohort study.

This multicohort study examined whether loneliness is associated with incident cardiometabolic disease (CMD) and cardiometabolic multimorbidity across 33 countries, and whether unhealthy lifestyle and socioeconomic status (SES) explain or amplify these relationships. Using data from six cohorts (CHARLS, ELSA, HRS, SHARE, KLoSA, MHAS), it assessed longitudinal links between loneliness and subsequent CMD outcomes while considering lifestyle and SES as potential mediators/moderators. The findings aim to clarify whether loneliness is a modifiable psychosocial risk factor for CMD across diverse populations, informing prevention strategies that integrate social and behavioral interventions.

Wang DY, Xie L, Wu Q et al. · European journal of preventive cardiology · (2026) · View on PubMed ↗

Obesity Management Pharmacotherapies and Lifestyle Treatment for Pediatric Obesity Management: A Systematic Review and Network Meta-Analysis.

This systematic review and network meta-analysis compared health behavior and lifestyle treatment (HBLT) versus obesity pharmacotherapies and their combinations for weight management in children and adolescents aged 10–19 years with obesity. Across randomized clinical trials, the relative effectiveness of specific pharmacotherapy options and combinations versus structured lifestyle treatment was synthesized to rank interventions for weight outcomes. These findings help clinicians and guideline developers choose among pediatric obesity treatment strategies beyond lifestyle alone, using comparative evidence from RCTs.

Wan KW, Lei EF, Liu Y et al. · JAMA pediatrics · (2026) · View on PubMed ↗

Consumption of Fructose-Containing Food and Beverage Sources in Childhood Through to Adulthood and Risk of Hypertension: A Prospective Cohort Study.

This prospective cohort study in the Growing Up Today Study (GUTS; 25,749 participants followed through 2021) assessed whether different childhood-to-adulthood sources of fructose-containing foods and beverages—sugar-sweetened beverages, fruit juices, and whole fruit—differentially predict incident hypertension. The key finding was that fructose-containing intake patterns across the life course were associated with later hypertension risk, with effects varying by beverage/food matrix rather than fructose alone. These results support more specific dietary guidance for preventing hypertension by targeting particular fructose sources during development.

Nguyen M, AlEssa HB, Glenn AJ et al. · Circulation · (2026) · View on PubMed ↗

FDA-approved antisense oligonucleotide therapies for duchenne muscular dystrophy: current status and future outlook.

This review summarized the current status and future outlook of FDA-approved antisense oligonucleotide (ASO) therapies for Duchenne muscular dystrophy (DMD), focusing on exon-skipping agents that restore dystrophin expression. It highlighted the four FDA-approved ASOs—eteplirsen, golodirsen, viltolarsen, and casimersen—and discussed their clinical trial development and post-marketing updates, along with remaining challenges in trial design and efficacy assessment. The significance is that it consolidates the evidence base for ASO exon-skipping strategies and frames next-step research needs to improve outcomes for DMD patients.

Moriyama H, Moriyama S, Yokota T · RNA biology · (2026) · View on PubMed ↗ · Free PDF ↗

Prediction of axial elongation in adults with high myopia: the Wenzhou High Myopia Cohort Study.

This prospective Wenzhou High Myopia Cohort Study followed 532 adults (1025 eyes; ages 18–60) with high myopia to identify predictors of rapid axial elongation (≥0.10 mm over 2 years). The study assessed nine candidate variables and used stepwise regression and discrimination metrics (e.g., AUC) to determine the optimal predictors for future axial growth. Clinically, improved prediction of axial elongation risk can enable earlier, more targeted interventions to reduce the likelihood of vision-threatening myopia complications.

Wang Y, Rui X, Sun Y et al. · Eye and vision (London, England) · (2026) · View on PubMed ↗ · Free PDF ↗

Development and validation of a prediction model for activities of daily living dysfunction among stroke survivors: insights from the CHARLS cohort.

This study developed and validated a prediction model for activities of daily living (ADL) dysfunction among stroke survivors using the CHARLS cohort, with 906 participants in training and 389 in validation. Using LASSO regression and multivariable logistic regression, the authors created a nomogram-based model to estimate ADL dysfunction risk. Scientifically and clinically, the model could support earlier identification of stroke survivors needing targeted rehabilitation to reduce disability burden.

Ren H, Wang W, Tao L et al. · Journal of neuroengineering and rehabilitation · (2026) · View on PubMed ↗ · Free PDF ↗

Consumption of sugar-sweetened beverages and all-cause mortality and cause-specific mortality: insights from nationwide prospective cohort studies and Global Burden of Disease study 2021.

This analysis combined nationwide prospective cohort data and Global Burden of Disease 2021 estimates to quantify dose-response associations between sugar-sweetened beverage (SSB) consumption and all-cause and cause-specific mortality. Using NHANES (n=13,438) and UK Biobank (n=63,436), the study estimated how varying SSB intake levels related to mortality risk and contextualized these findings with national burden trends from 1990–2021. The results inform public health policy by clarifying the magnitude of mortality risk associated with SSB consumption across populations.

Tan X, Chi K, Lai C et al. · Diabetology & metabolic syndrome · (2026) · View on PubMed ↗ · Free PDF ↗

Prevention, Screening, Diagnosis, and Treatment of Iron Deficiency and Iron Deficiency Anemia in Infants, Children, and Adolescents: Clinical Report.

This Pediatrics clinical report reviewed prevention, screening, diagnosis, and treatment strategies for iron deficiency (ID) and iron deficiency anemia (IDA) in infants, children, and adolescents. It emphasizes history and physical exam features plus targeted laboratory testing, and provides treatment recommendations tailored to nutritional ID/IDA and causes such as malabsorption or blood loss (including heavy menstrual or gastrointestinal bleeding). The report’s significance is to standardize care pathways that reduce missed diagnoses and optimize iron repletion across pediatric age groups.

Powers JM, Heeney MM, Hord J et al. · Pediatrics · (2026) · View on PubMed ↗

Physical exercise mitigates amyloid beta-driven muscle degeneration in Alzheimer’s disease.

This study investigated molecular mechanisms of amyloid-β (Aβ)-driven skeletal muscle degeneration in an Alzheimer’s disease context and tested whether high-intensity interval training (HIIT) can mitigate muscle dysfunction in a small exploratory clinical cohort and supporting experiments. It found that HIIT alleviated Aβ-associated muscle degeneration and improved related pathological and functional outcomes compared with non-exercised controls. The clinical significance is that exercise—specifically HIIT—may counter peripheral Aβ-driven frailty and functional decline, supporting AD as a systemic disease with modifiable muscle pathology.

Yang LL, Luo YX, Song D et al. · Journal of advanced research · (2026) · View on PubMed ↗ · Free PDF ↗

Early-life musical intervention programs neuroimmune activity and synaptic plasticity to enhance adult learning and memory.

This animal study tested whether early-life graded musical brain intervention (MBI) during embryonic and early postnatal periods alters adult learning and memory by modulating neuroimmune activity and synaptic plasticity in C57BL/6J mice. It found that MBI produced exposure-dependent changes in adult cognitive performance alongside corresponding shifts in immune/neuroimmune markers and synaptic plasticity measures. The significance is that early auditory enrichment can program long-term brain function through neuroimmune–synaptic mechanisms, informing developmental interventions for cognitive outcomes.

Qiu R, Fu Q, Yao T et al. · Brain, behavior, and immunity · (2026) · View on PubMed ↗

Investigating the effects of antidepressants on measures of insulin resistance in major depressive disorder: A systematic review.

This systematic review evaluated clinical trials and other studies reporting how antidepressants affect insulin resistance measures in people with major depressive disorder (MDD). It synthesized evidence to disaggregate class- and drug-specific effects on insulin resistance risk, addressing the observation that insulin resistance can blunt acute antidepressant response while some antidepressants may worsen insulin resistance. The significance is that it supports more precise selection and monitoring of antidepressant therapy in MDD patients at metabolic risk.

Wong S, Le GH, Zheng YJ et al. · Journal of affective disorders · (2026) · View on PubMed ↗ · Free PDF ↗

Progestin therapy in premenopausal women with incidental meningioma-a narrative review and recommendations for women’s health specialists.

This narrative review evaluated evidence from 2015–2025 studies on how exogenous progestins (including different compounds and cumulative exposure) relate to meningioma development, growth, and progression in women. Overall, it synthesizes findings and proposes practical recommendations for women’s health specialists on hormonal management when progestin therapy is needed. Clinically, the review aims to support safer prescribing by balancing therapeutic indications against potential meningioma risk in premenopausal women.

Pluchino N, Vibert J, Roth M et al. · Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗

Effects of Different Training Modalities on Circulating Irisin Levels in Overweight and Obesity Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

This systematic review and meta-analysis of randomized controlled trials evaluated how different exercise training modalities affect circulating irisin levels in overweight and obese adults. It pooled evidence to determine whether exercise type (training modality) produces consistent changes in irisin and related metabolic markers. The findings are intended to clarify exercise-induced myokine responses and inform exercise prescription for metabolic health in adults with overweight/obesity.

Hejazi K, Mohammad Rahimi GR, Saeidi A et al. · Sports medicine (Auckland, N.Z.) · (2026) · View on PubMed ↗

Irisin treatment counteracts bone loss and muscle atrophy in aged mice by reducing sclerostin expression in bone and skeletal muscle.

This preclinical study tested whether chronic irisin treatment counteracts age-related osteosarcopenia in 12-month-old C57BL/6 mice. Irisin administered subcutaneously (100 µg/kg weekly) for 8 months reduced bone loss and muscle atrophy and decreased sclerostin expression in both bone and skeletal muscle. These results support irisin as a potential therapeutic candidate for mitigating osteosarcopenia by targeting sclerostin-mediated pathways.

Suriano C, Zerlotin R, Taurino M et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Integrated proteomic and metabolomic analyses implicate redox-metabolic pathways in PTSD-associated multisystem disease and accelerated aging.

The study analyzed plasma proteomics and targeted metabolomics to identify redox-metabolic pathways underlying PTSD-associated multisystem disease and accelerated aging in World Trade Center responders. In 393 participants (232 with PTSD, 161 trauma-exposed controls), 114 proteins and seven metabolites differed in PTSD, and integrative proteomic–metabolomic correlations implicated coordinated redox-metabolic alterations involving metabolites such as serotonin, lactate, glutamic acid, and cystathionine. These findings provide molecular candidates linking PTSD to systemic comorbidity and premature aging, supporting pathway-focused biomarker and intervention development.

Kuan PF, Mann FD, Yang X et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on June 23, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.