PubMed Trending Research Digest — September 21, 2026

Automated digest · 96 articles · 15 research areas · September 21, 2026

Overview

This week’s digest is dominated by a convergence theme: immune function and disease progression are increasingly being explained through dynamic, systems-level biology—especially in cancer and chronic inflammatory disorders. Multiple studies emphasize that immune responses are not static “on/off” states. Instead, T-cell exhaustion/senescence trajectories, checkpoint resistance via immune-pressure redistribution, and tumor microenvironment remodeling (including metabolic lipid programs) all point toward therapies that reprogram immune states rather than simply block a single pathway.

A second major thread is metabolic control—both as a driver of disease and as a therapeutic lever. In oncology, work on glycolytic reprogramming (e.g., ZMIZ1–NOTCH1–PYCR1), lipid droplet formation (MAL2–ncNF-κB–FASN), and cancer stem cell metabolic flexibility highlights how tumors evade immunity and resist therapy. Outside cancer, studies on GLP-1–based obesity treatment (including oral GLP-1 agonism and tirzepatide’s abdominal fat effects), gut–liver metabolic inflammation (probiotic modulation in MASLD), and energy-sensing/circadian coupling (AMPK–NPAS2 in human muscle) reinforce that metabolic pathways are central to both prevention and treatment.

Finally, translational innovation shows up across modalities: targeted delivery (CD20 nanomedicine engaging cGAS/STING), improved drug design (PROTAC linker principles), and gene-editing approaches (CRISPR strategies for sickle cell and astrocyte-specific GFAP disruption). In parallel, real-world and safety-focused evidence—such as survivorship toxicity after melanoma immunotherapy, pharmacovigilance of BTK inhibitors, and adverse-effect considerations for CNS-active therapies—underscores that modern medicine is moving toward more personalized, mechanism-informed, and patient-centered care.

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Oncology biomarkers, risk prediction, and prognostic modeling

Development and Validation of an Interpretable Machine Learning Model for Predicting Early Pulmonary Metastasis Risk in Osteosarcoma.

This retrospective study analyzed 522 patients with high-grade conventional osteosarcoma to develop and validate an interpretable machine-learning model using multi-dimensional electronic medical record (EMR) data to predict early pulmonary metastasis risk. The model identified 12 independent predictive factors (including prothrombin time [PT] and international normalized ratio [INR]) and was designed to stratify patients by early metastasis risk. Clinically, an interpretable EMR-based risk tool could enable earlier identification of patients likely to develop lung metastases and support more timely surveillance or treatment intensification.

Mu J, Wang Y, Liu H et al. · Cancer medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Prophylactic cranial irradiation versus active MRI surveillance for limited-stage small-cell lung cancer achieving response after chemoradiotherapy: a protocol for a randomized, controlled, multicenter, phase III trial.

This protocol study will enroll contemporary limited-stage small-cell lung cancer (LS-SCLC) patients who achieved a response after chemoradiotherapy to compare prophylactic cranial irradiation (PCI) versus active MRI surveillance in a randomized, multicenter phase III trial. The primary aim is to determine whether active MRI surveillance is non-inferior to PCI for overall survival (OS) while addressing uncertainty from the pre-MRI era and potential neurocognitive toxicity of PCI. If successful, the trial will directly inform modern standard-of-care decisions for brain relapse prevention in LS-SCLC using MRI-guided management.

Wei Z, Chen Y, Yu J et al. · Respiratory research · (2026) · View on PubMed ↗ · Free PDF ↗

Beyond the blood-brain barrier: humanised mice, the missing link in glioblastoma research.

This article discusses the rationale for using humanised mouse models as a more translational preclinical platform for glioblastoma (GBM) research beyond conventional animal models and ex vivo systems. The key finding is that humanised mice can better recapitulate aspects of the human tumor microenvironment (TME) and immune context that are inadequately modeled in standard systems. The scientific significance is that it positions humanised mice as a “missing link” to improve evaluation of GBM biology and therapeutic efficacy in settings closer to human disease.

Shirazi Nia R, Lu J, De Vega D et al. · Oncogene · (2026) · View on PubMed ↗ · Free PDF ↗

Efficacy and safety of omitting the clinical target volume in limited-stage small cell lung cancer: a large-scale multicenter real-world study.

This multicenter real-world study evaluated whether omitting the clinical target volume (CTV) in limited-stage small cell lung cancer (LS-SCLC) can reduce toxicity without compromising efficacy in 946 patients treated between 2016 and 2025. The key finding is that patients managed with an “Omit-CTV” approach (n=403) were compared against conventional CTV delineation (n=543) to assess outcomes and an exploratory contemporary immunotherapy subgroup effect, with results reported as part of the study’s primary objective (details truncated). If effective, CTV omission could simplify radiotherapy planning and lower treatment-related toxicity in LS-SCLC.

Wang X, Yu X, Liu X et al. · Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · (2026) · View on PubMed ↗

Non-Cystic Fibrosis Bronchiectasis in the United States: Prevalence Trends in a Large Electronic Health Record Population, 2015-2025.

This retrospective repeated cross-sectional analysis quantified prevalence trends of non-cystic fibrosis bronchiectasis in a large US primary care electronic health record population from 2015–2025. Using Epic Cosmos data covering over 307 million de-identified patients, the study assessed how prevalence changed over time and varied by demographics and subspecialist evaluation. The results are intended to refine estimates of disease burden and inform healthcare planning and epidemiologic understanding of bronchiectasis in the general US population.

Jung F, MacRae S · Chest · (2026) · View on PubMed ↗

Biomarkers associated with efficacy of first-line nivolumab vs. sorafenib in advanced hepatocellular carcinoma: results from the CheckMate 459 phase III trial.

This exploratory biomarker analysis from the CheckMate 459 phase III trial compared first-line nivolumab versus sorafenib in advanced hepatocellular carcinoma (HCC) using tumor and blood assays. Using whole-exome sequencing, whole-transcriptome RNA sequencing, immunohistochemistry, and serology on pre-treatment samples, the study assessed biomarkers associated with objective response rate (ORR) and progression-free survival (PFS). The significance is that it seeks to identify molecular predictors of benefit from nivolumab over sorafenib, enabling more personalized first-line therapy in advanced HCC.

Neely J, Yao J, Kudo M et al. · JHEP reports : innovation in hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Sobering Outcomes after Two-Stage Revision for Periprosthetic Joint Infection Among Patients Who Have Revision Total Knee Arthroplasty Components.

This retrospective study assessed outcomes after two-stage revision for periprosthetic joint infection (PJI) among patients undergoing revision total knee arthroplasty (TKA) with complete implant removal. The key finding was that explantation-based two-stage revision outcomes were suboptimal (“sobering”), reflecting persistent morbidity and failure risk in this high-acuity population. Clinically, the results help set realistic expectations and inform decision-making and optimization of PJI management strategies after revision TKA.

Ball JR, Palmer RC, Telang SS et al. · The Journal of arthroplasty · (2026) · View on PubMed ↗

Chronic hepatitis B and perioperative chemotherapy efficacy in colorectal liver metastases: an exploratory analysis of clinical and mechanistic evidence.

This exploratory retrospective analysis studied whether perioperative or adjuvant chemotherapy affects disease-free survival in 822 patients with chronic hepatitis B (CHB) undergoing curative resection of colorectal liver metastases (CRLM), and used mechanistic approaches to explain efficacy differences. It found that CHB status and perioperative/adjuvant chemotherapy timing were associated with differences in DFS, and that single-cell RNA sequencing and tumor-derived organoids supported mechanistic links between CHB-related immune/tumor microenvironment features and chemotherapy response. The study is significant because it combines clinical outcomes with single-cell and organoid evidence to inform chemotherapy selection and perioperative strategy in CHB-associated CRLM.

Cheng CL, Tong SY, Mo SB et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Hyperdiploid multiple myeloma: A heterogeneous entity requiring refined risk stratification-Insights from chromosome count and cytogenetic abnormalities.

This study analyzed hyperdiploid multiple myeloma (MM) prognostic heterogeneity in 694 newly diagnosed Chinese patients using integrated single-nucleotide polymorphism (SNP) array and fluorescence in situ hybridization (FISH) to quantify chromosome counts and cytogenetic abnormalities. A modal chromosome count >49 predicted better overall survival (OS) and progression-free survival (PFS), and gain of chromosome 3 was additionally favorable, while hyperdiploidy improved OS only in patients with isolated 1q21+ but not in those with high-risk lesions such as t(4;14), t(14;16), 17p deletion, or 1p32 deletion. These findings support refined risk stratification of hyperdiploid MM by combining chromosome count with specific FISH-defined high-risk events to better guide clinical prognosis.

Zeng Z, Lu J, Shang J et al. · British journal of haematology · (2026) · View on PubMed ↗

Multivariate Survival Analysis of a Comprehensive Clinical Trial of Rapamycin in Amyotrophic Lateral Sclerosis Explores Prognostic Factors and Survival Patterns in C9orf72 Carriers.

This retrospective survival analysis used regularized Cox regression with time-dependent covariates on longitudinal data from the RAP-ALS clinical trial (n=63) to evaluate prognostic factors and survival patterns in amyotrophic lateral sclerosis (ALS) patients carrying C9orf72 expansions treated with rapamycin. The study identified multivariable risk/protective factors associated with survival and characterized how these factors changed over time in C9orf72 carriers under rapamycin exposure. Clinically, this helps define which patient characteristics may predict response or outcomes in rapamycin-treated C9orf72-ALS, informing future stratified trial design.

De Nardi A, Paris A, Lauria M et al. · European journal of neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Serum Metabolomic Profiles Unveil Biomarkers and Core Metabolic Pathways in Multiple System Atrophy Patients.

This study used untargeted serum metabolomics with UHPLC-Q-Exactive HF mass spectrometry to characterize metabolic pathways and identify biomarkers in 85 multiple system atrophy (MSA) patients versus 85 healthy controls. The authors reported metabolomic profiles that reveal disease-associated biomarkers and core metabolic pathway alterations distinguishing MSA from controls. Scientifically, these findings advance biomarker discovery and may help clarify MSA pathophysiology to support earlier diagnosis and future therapeutic targeting.

Wan L, Chen Z, Wan N et al. · Movement disorders : official journal of the Movement Disorder Society · (2026) · View on PubMed ↗

Beyond the Surface of Long-term Survival in Stage IV Melanoma: A Multicenter Cross-sectional Study.

This multicenter cross-sectional study examined long-term survivors of stage IV metastatic melanoma (overall survival >5 years) using an online survey to characterize treatment-related adverse events (TRAEs), psycho-oncological distress, and socioeconomic outcomes. The key finding was that long-term survivors experience a measurable spectrum of TRAEs and distress, with results used to assess whether elevated distress is common enough to justify dedicated survivorship programs. Clinically, the findings support the implementation of structured melanoma survivorship care to address ongoing toxicity and psychosocial needs after immune checkpoint inhibitor and targeted therapy.

Reitmajer M, Livingstone E, Schäffeler N et al. · The British journal of dermatology · (2026) · View on PubMed ↗

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Diabetes, kidney disease, and metabolic comorbidity

Ovarian tumor domain-containing protein 1 deficiency attenuates metabolic dysfunction-associated steatotic liver disease by promoting the ubiquitination of HSP90α in hepatocytes.

This study investigated the role of ovarian tumor domain-containing protein 1 (OTUD1) in metabolic dysfunction-associated steatotic liver disease (MASLD) using human liver samples, two GEO cohorts (GSE24807 and GSE126848), and high-fat diet (HFD) mouse models including systemic Otud1 knockout mice. OTUD1 deficiency attenuated MASLD features by improving insulin resistance and inflammation and promoting ubiquitination of HSP90α in hepatocytes. These findings suggest OTUD1–HSP90α axis modulation as a potential therapeutic strategy for MASLD.

Huang MQ, Wei SY, Li MZ et al. · Molecular biomedicine · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative Incidence of Urinary Tract Infections in Diabetic Women Treated with Dapagliflozin Versus Empagliflozin: A Double-Blind Randomized Clinical Trial.

In a randomized, double-blind clinical trial of 149 women with type 2 diabetes (dapagliflozin 5 mg, n=79 vs empagliflozin 10 mg, n=70 for 3 months), investigators compared urinary tract infection (UTI) incidence and monitored metabolic and renal parameters. The trial found a differential UTI incidence between the two SGLT2 inhibitors over the treatment period. If confirmed in broader populations, these data could inform safer SGLT2 inhibitor selection for diabetic women at risk of UTIs.

Kazem-Nadi S, Keshtkari S, Labbani-Motlagh Z et al. · International journal of endocrinology and metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Spermidine attenuates monocrotaline-induced pulmonary arterial hypertension with HADHA-associated improvements in fatty acid oxidation and mitochondrial redox homeostasis.

This study examined whether spermidine (SPD) can attenuate monocrotaline-induced pulmonary arterial hypertension (PAH) and whether effects involve HADHA-linked mitochondrial fatty acid oxidation and redox homeostasis, using integrated metabolomics/lipidomics and mechanistic experiments. SPD improved PAH-associated mitochondrial redox imbalance and metabolic dysfunction in association with HADHA-related enhancement of fatty acid β-oxidation and mitochondrial quality control/mitophagy-related pathways. The results suggest a mitochondria-targeted, HADHA-associated mechanism by which SPD may be therapeutically beneficial in PAH.

Bai X, Tian K, Song S et al. · Redox biology · (2026) · View on PubMed ↗ · Free PDF ↗

Chemical characterization and pharmacological mechanisms of Qizhi Yishen Capsule in early diabetic kidney disease.

This study characterized the bioactive components and proposed molecular mechanisms of the Qizhi Yishen Capsule (QZC) for early diabetic kidney disease (DKD) by combining network pharmacology and molecular docking with rat DKD experiments. QZC reduced renal injury in DKD rats and modulated candidate targets and metabolic pathways identified in silico, supported by serum biochemistry, histology, transmission electron microscopy, metabolomics, and in vitro validation. These data provide preclinical mechanistic support for QZC as a multi-target therapy for early DKD and help prioritize pathways for future translational testing.

Duan W, Jiang Q, Shang G et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

Adverse event reporting signals for SGLT-2 inhibitor-metformin combination therapy: a disproportionality analysis of the FAERS database.

This disproportionality analysis studied real-world adverse event (AE) reporting for SGLT-2 inhibitor plus metformin combination therapy versus monotherapy using the U.S. FDA Adverse Event Reporting System (FAERS) from Q1 2013 through Q4 2025. It found safety signals for specific AEs associated with the combination regimens (including ertugliflozin, dapagliflozin, empagliflozin, or canagliflozin plus metformin) relative to comparator patterns, quantified using reporting odds ratio (ROR) and proportional reporting ratio (PRR) approaches. The findings are significant because they help clinicians and regulators identify potential combination-specific risks that warrant further pharmacoepidemiologic validation.

Zhou W, Xia Y, Li J et al. · Frontiers in endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗

SGLT2 versus DPP-4 inhibitors in type 2 diabetes: a meta-analysis of outcomes.

This meta-analysis studied randomized controlled trials comparing SGLT2 inhibitors (SGLT2i) versus DPP-4 inhibitors (DPP4i) in type 2 diabetes with outcomes including glycemic control, weight change, and genital infection risk. It found differential effects favoring SGLT2i for weight reduction and glycemic outcomes while characterizing genital infection risk relative to DPP4i across pooled RCT evidence. The results are significant because they support individualized medication selection by quantifying trade-offs between metabolic benefits and infection risk.

Fang X, Li R, Liu S et al. · Frontiers in endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗

Case Report: Reopening the anabolic window - romosozumab added to ongoing denosumab for severe osteoporosis in two kidney transplant recipients.

This case report studied two female kidney transplant recipients with severe osteoporosis and persistently high fracture risk despite long-term denosumab, where romosozumab (210 mg monthly) was added to ongoing denosumab for 12 months. It found improvements in bone-formation marker P1NP (and related bone turnover measures) during the combined anabolic/antiresorptive approach. The report is significant because it suggests a potential strategy to “reopen the anabolic window” in transplant-associated osteoporosis, a setting where evidence for romosozumab—especially in combination with denosumab—is limited.

Barbuto S, Mastromauro P, Zavatta G et al. · Frontiers in endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗

Effects of Lactobacillus acidophilus on hepatic and microbial dysregulation in MASLD and diabetes.

This work tested whether Lactobacillus acidophilus supplementation can modulate hepatic and gut microbial dysregulation across metabolic dysfunction-associated steatotic liver disease (MASLD) and diabetes using multiple diet-induced models (western diet, fructose-palmitate-cholesterol diet, high-fat diet) and leptin-deficient ob/ob mice. L. acidophilus attenuated hepatic steatosis and inflammatory injury and improved disease-associated microbial dysbiosis patterns across the disease continuum. These results support L. acidophilus as a candidate probiotic strain for mechanistic and translational studies targeting gut-liver metabolic inflammation in MASLD with diabetes.

Park HJ, Park IG, Park JH et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

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Autoimmune and inflammatory disease immunobiology

Pulmonary Function in Adults with Severe Eosinophilic Asthma Using Biologicals:A Case-Control Study.

This case-control study compared pulmonary function in 32 adults with severe eosinophilic asthma (15 using biologics vs 17 on conventional therapy) using comprehensive measurements of pulmonary mechanics, static lung volumes, and small airways. Adults receiving biologics showed differences in pulmonary function compared with those on conventional therapy, indicating that biologic treatment is associated with measurable changes across multiple lung compartments. The results support more detailed physiologic assessment of severe eosinophilic asthma beyond symptom control when evaluating biologic effectiveness.

Beserra ADS, Borges JR, Ferreira IDN et al. · Current health sciences journal · (2026) · View on PubMed ↗ · Free PDF ↗

Autosomal dominant gain-of-function mutations in LCP1 cause a syndromic neutropenia and immunodeficiency.

This genetic and mechanistic study identified three patients with heterozygous LCP1 gain-of-function mutations (L362F, A365D) causing activated LCP1-associated immunodeficiency syndrome, characterized by congenital neutropenia and variable combined immunodeficiency. Patient-derived iPSCs, CRISPR-edited cells, and LCP1+/L362F mice replicated the phenotype, and mutant LCP1 was shown to hyper-bundle F-actin, trigger VDAC1 oligomerization, and drive mitochondrial apoptosis. These findings establish LCP1 as a regulator of immune cell fate and clarify a pathway that could guide targeted interventions for this immuno-actinopathy.

Yu L, Zhou B, Liu W et al. · Genes & diseases · (2027) · View on PubMed ↗ · Free PDF ↗

High-throughput chemical screen identifies epothilone B in modulating inflammatory bowel disease by triggering neutrophil apoptosis.

This study performed a high-throughput chemical screen to identify compounds that modulate inflammatory bowel disease (IBD) by affecting neutrophil apoptosis. It identified epothilone B as a candidate that triggers neutrophil apoptosis, aiming to recalibrate neutrophil responses to reduce inflammatory damage in IBD. The scientific significance is that epothilone B may represent a strategy to restore appropriate neutrophil turnover rather than broadly suppressing neutrophil function.

He Z, Deng Z, Zhang H et al. · Genes & diseases · (2027) · View on PubMed ↗ · Free PDF ↗

Elevated ISG15 reinforces RIG-I/MDA5-linked macrophage-microglia crosstalk during blood-brain barrier disruption in neuromyelitis optica spectrum disorder.

This study investigated the role of interferon-stimulated gene 15 (ISG15) in reinforcing RIG-I/MDA5-linked macrophage–microglia crosstalk during blood–brain barrier disruption in neuromyelitis optica spectrum disorder (NMOSD). Using single-cell RNA sequencing of PBMCs from NMOSD patients plus mechanistic experiments in THP-1-derived macrophages and HMC3/BV2 microglia with ISG15 knockdown/overexpression, the authors report that elevated ISG15 strengthens myeloid activation via RLR signaling and promotes microglial polarization during BBB injury. These results identify ISG15–RLR pathway signaling as a potential therapeutic axis to dampen neuroinflammation in NMOSD.

Niu Y, Sun J, Han Y et al. · International immunopharmacology · (2026) · View on PubMed ↗ · Free PDF ↗

Evaluation of eculizumab for the prevention of delayed graft function after kidney transplantation in adults: A randomized, double-blind, placebo-controlled trial.

This randomized, double-blind, placebo-controlled trial tested whether eculizumab prevents delayed graft function (DGF) after kidney transplantation in adults receiving expanded criteria donors. The key finding is that eculizumab did not statistically significantly reduce DGF compared with placebo (with dosing given immediately before and 18–24 hours after transplant). Clinically, the trial suggests that complement inhibition with eculizumab is not an effective standalone strategy to prevent DGF in adult kidney transplant recipients.

Marks WH, Patel A, Viklicky O et al. · American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · (2026) · View on PubMed ↗

Endometriosis from Initiation to Innovation: Immune Microenvironments, Clonal Lesion Biology, and the Emerging Therapeutic Pipeline.

This article reviewed endometriosis from initiation to innovation, focusing on immune microenvironments and clonal lesion biology, particularly in ovarian endometriosis. It highlights that endometriosis lesions show cancer-relevant behaviors such as clonal expansion, somatic alteration-associated evolution, invasion, apoptosis resistance, immune evasion, angiogenesis, fibrosis, and metabolic adaptation. The significance is that treating endometriosis using an oncologic framework may reveal new biomarkers and therapeutic targets to prevent progression and reduce malignant transformation risk.

Santhamma B, Chacon J, Deemer E et al. · Cancer letters · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting epithelial IFN-I signaling restores barrier integrity in anti-TNF refractory Crohn’s disease.

This study investigated epithelial type I interferon (IFN-I) signaling and epithelial TNF–IFN-I crosstalk as drivers of epithelial dysfunction and anti-TNF non-response in Crohn’s disease (CD) using human biopsies, single-cell RNA sequencing, and murine TNFR1-deficient models plus patient-derived organoids. Anti-TNF non-responders showed enrichment of IFN-I–related epithelial programs, and restoring epithelial IFN-I signaling improved barrier integrity in organoid and in vivo systems exposed to inflammatory cytokines and clinically relevant treatments. These findings support epithelial IFN-I pathway modulation as a potential strategy to overcome anti-TNF refractory CD.

Gadeock S, King M, Polk DB et al. · Journal of Crohn’s & colitis · (2026) · View on PubMed ↗ · Free PDF ↗

Community Pharmacist Support for Complex Palliative Pharmacotherapy and Home Infusion in Advanced Heart Failure: A Case Report.

This case report described community pharmacist support for complex palliative pharmacotherapy and home infusion in a 76-year-old man with stage D advanced heart failure requiring inotrope dependence. Pharmacist involvement before discharge supported safe management of injectable drugs, infusion devices/compatibility, and symptom monitoring as part of an interdisciplinary end-of-life care plan. The report is clinically significant because it documents practical pharmacist-led processes that may improve safety and feasibility of home infusion palliative care in advanced heart failure.

Suzuki H, Mori M, Hattori Y et al. · Journal of pain & palliative care pharmacotherapy · (2026) · View on PubMed ↗

Fungal extracellular vesicles reshape Lactobacillus rhamnosus vesicles to enhance lysosomal homeostasis and resolve intestinal inflammation.

The study investigated how fungal extracellular vesicles (EVs) condition Lactobacillus rhamnosus EV biogenesis and function using a defined in vitro conditioning system and comparative proteomics/lipidomics. Exposure to fungal EVs reprogrammed L. rhamnosus to produce ScEV-conditioned vesicles (ScEV-LrEVs) with extensively remodeled cargo, including ~60-fold enrichment of hydroxylated ceramide Cer(t18:0/24:0(2OH)), and these vesicles showed enhanced anti-inflammatory activity in LPS-stimulated macrophages. This suggests an interkingdom EV “reprogramming” mechanism that could be leveraged to improve lysosomal homeostasis and resolve intestinal inflammation in inflammatory bowel disease contexts.

Ji Z, Chen G, He X et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

Autoimmune inflammatory diseases of the central nervous system: advances in clinical trials and immunotherapeutic strategies.

This review studied autoimmune inflammatory diseases of the central nervous system—autoimmune encephalitis (AE), neuromyelitis optica spectrum disorder (NMOSD), and MOG antibody-associated disease (MOGAD)—with emphasis on advances in clinical trials and immunotherapeutic strategies. It finds that defining disease by specific autoantibody targets and clinical phenotypes has shifted management toward mechanism-based immunotherapy, although these disorders remain rare, heterogeneous, and often severe. The significance is improved trial design and therapeutic selection based on immunologic mechanisms, which is critical for developing more effective treatments for these CNS autoimmune conditions.

Gumienny M · Reumatologia · (2026) · View on PubMed ↗ · Free PDF ↗

The plasticity and metabolic reprogramming of macrophage in ulcerative colitis.

This article reviewed how macrophage plasticity and metabolic reprogramming shape ulcerative colitis (UC) pathogenesis and repair, focusing on tissue-resident versus monocyte-derived intestinal macrophages. It highlights that glucose-driven metabolic switching (e.g., glycolysis promoting M1-like polarization) and mitochondria-associated reactive oxygen species (ROS) production influence macrophage fate in UC. Scientifically, it frames metabolic pathways as actionable regulators of inflammatory versus reparative macrophage states in UC.

Zhang Y, Yang D, Jiang J et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Rituximab With or Without Avacopan in ANCA-Associated Vasculitis With Severe Renal Involvement.

This retrospective comparative cohort study examined patients with ANCA-associated vasculitis (AAV) and severe renal involvement (eGFR <30 ml/min per 1.73 m2 at induction) treated with rituximab plus avacopan versus rituximab alone at Mayo Clinic. It found differences in time to renal remission—defined by limited eGFR decline and controlled hematuria—between the two treatment strategies using Kaplan–Meier and Cox analyses. The study is clinically significant because it addresses whether avacopan provides additional renal benefit as a glucocorticoid-sparing therapy when rituximab is used for induction in high-severity AAV.

Juanet C, Hassi I, Cara A et al. · Kidney international reports · (2026) · View on PubMed ↗ · Free PDF ↗

Entering the era of disease modification in Crohn’s disease.

This narrative review examined evidence for disease modification in Crohn’s disease, focusing on early intervention strategies and distinguishing short-term inflammatory control from durable alteration of disease course. It synthesizes data on early medical and surgical approaches and discusses the “window of opportunity” concept for changing long-term outcomes. Clinically, the review supports treatment paradigms that aim to modify disease trajectory rather than only manage symptoms.

Gros B, Derikx LAAP, Truyens M et al. · Expert review of clinical pharmacology · (2026) · View on PubMed ↗

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Nanomedicine and targeted drug delivery

Mechanistic Insights and Therapeutic Potential of Plant-Derived Exosome-Like Nanovesicles in Skin Tissue Regeneration.

This article reviewed plant-derived exosome-like nanovesicles (PENs) and their mechanisms in skin tissue regeneration, focusing on their lipid bilayer nanostructure and natural bioactive cargo. It highlights that PENs may provide advantages over mammalian or microbial extracellular vesicles, including scalable production, biosafety, and low immunogenicity, while supporting multiple regenerative roles in skin. Scientifically, PENs are positioned as a promising nanotherapeutic platform for advancing regenerative medicine and skin barrier repair.

Ma X, Shi J, Li R et al. · International journal of nanomedicine · (2026) · View on PubMed ↗ · Free PDF ↗

CD20 targeted nanomedicine enhances anti-tumor immunity in diffuse large B-cell lymphoma by activating cGAS/STING pathway.

This study investigated a CD20-targeted nanomedicine in diffuse large B-cell lymphoma (DLBCL) to determine whether it enhances anti-tumor immunity via activation of the cGAS/STING pathway. The key finding was that CD20-targeted delivery increased cGAS/STING pathway activation, promoting stronger anti-tumor immune responses in the DLBCL setting. This suggests a clinically relevant immunotherapeutic strategy that couples B-cell targeting (CD20) with innate immune pathway stimulation (cGAS/STING) to improve outcomes in DLBCL.

Chi Z, Xu N, Sun Y et al. · Cancer letters · (2026) · View on PubMed ↗

From discovery to clinic: Medicinal chemistry strategies for PROTAC linker optimization.

This review studied medicinal chemistry strategies for optimizing PROTAC linkers, focusing on structure–activity relationships derived from clinical-stage PROTAC candidates. It found that linker physicochemical properties—such as alkyl chain rigidification, heteroatom incorporation, and conformational control—strongly influence target engagement, degradation potency, and pharmacokinetics/oral bioavailability. The synthesis provides actionable design principles to improve PROTAC drug-like behavior and accelerate translation of protein degraders to the clinic.

Yang H, Gu M, Li Z et al. · European journal of medicinal chemistry · (2026) · View on PubMed ↗

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Neuroimaging and CNS effects of therapeutics

Auvelity (Dextromethorphan-Bupropion) for Agitation and Aggression in Alzheimer’s Disease Dementia: Mechanism, Efficacy, Safety, and Clinical Considerations.

This article reviewed the mechanism, efficacy, safety, and clinical considerations of Auvelity (dextromethorphan–bupropion) for agitation and aggression in Alzheimer’s disease dementia. It describes how bupropion inhibits CYP2D6 to raise dextromethorphan exposure, with dextromethorphan acting as an uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist to promote synaptic plasticity. The clinical significance is that Auvelity may offer a non-antipsychotic option for distressing behavioral symptoms while addressing safety concerns associated with off-label atypical antipsychotics.

Sarangal M, Sarangal C, Vora J et al. · Psychopharmacology bulletin · (2026) · View on PubMed ↗ · Free PDF ↗

Gabapentin-Induced Severe Vivid Nightmares: A Case Series and Brief Review.

This case series reported two patients treated with gabapentin for spinal pain syndromes who developed severe vivid nightmares, and it briefly reviewed related literature on gabapentin’s effects on sleep. In both cases, discontinuation of gabapentin and transition to pregabalin led to resolution of nightmares. The report emphasizes a potentially underrecognized psychiatric adverse effect of gabapentin that clinicians should consider to improve adherence and quality of life.

Hasoon J, Nguyen A, Safabakhsh NA et al. · Psychopharmacology bulletin · (2026) · View on PubMed ↗ · Free PDF ↗

Sex-specific patterns of symptom burden, psychological distress, and work productivity impairment in post-acute sequelae of COVID-19: a 10-month dynamic cohort study.

This prospective 10-month dynamic cohort study followed post-acute sequelae of COVID-19 (PASC) patients with ongoing symptoms after confirmed SARS-CoV-2 infection to characterize sex-specific trajectories of symptom burden, psychological distress, work productivity impairment, and physical activity. The key finding is that symptom and psychosocial outcomes evolve differently by sex over time during the post-acute period. Scientifically and clinically, these longitudinal sex-specific patterns can guide more tailored follow-up and interventions for PASC patients.

Sauer A, Boblitz L, Drick N et al. · BMC pulmonary medicine · (2026) · View on PubMed ↗ · Free PDF ↗

A circuit dissection of perception-action decoupling in S-ketamine-induced hallucination-like states.

This mouse study dissected circuit mechanisms underlying perception–action decoupling in S-ketamine-induced hallucination-like states using an auditory discrimination task combined with AI-based pose analysis. The key finding is that S-ketamine produces false auditory threat responses and behavioral disorganization that are not attributable to anhedonia, anesthesia, or basic auditory deficits, and that specific neural pathways causally contribute as revealed by in vivo fiber photometry, single-cell miniscope calcium imaging, and pathway-specific chemogenetic/optogenetic manipulations. The significance is that it provides a circuit-level model for hallucination-like behavior that can guide targeted neuropsychiatric interventions.

Wang D, Xu J, Wang Z et al. · Molecular psychiatry · (2026) · View on PubMed ↗

An mPFC-DMV cortical-autonomic-immune axis governs stress-induced immune dysregulation in sepsis.

This mouse study tested whether chronic psychological stress worsens sepsis outcomes and identified the neural circuitry involved by using chronic restraint stress (CRS) followed by endotoxemia. The key finding is that prior stress aggravates mortality, systemic inflammation, and immune imbalance in sepsis, mediated by a stress-sensitive medial prefrontal cortex (mPFC)–dorsal motor nucleus of the vagus (DMV) circuit that regulates peripheral neuroimmune homeostasis. Clinically, defining this mPFC–vagus axis provides a mechanistic target for interventions aimed at reducing stress-associated immune dysregulation in sepsis.

Yin L, Liu F, Li M et al. · Molecular psychiatry · (2026) · View on PubMed ↗

Neuropsychiatric adverse effects following switch to vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: early experience from a regional centre.

This early regional-center experience evaluated neuropsychiatric adverse effects after switching adults with cystic fibrosis to the triple CFTR modulator vanzacaftor–tezacaftor–deutivacaftor (VTD). The authors found that among 87 adults started on VTD, two of three patients with pre-existing mental health conditions improved on a reduced VTD dose with no reported adverse effects, while the remaining patients’ outcomes were not fully detailed in the truncated abstract. Clinically, the report provides preliminary real-world guidance that VTD may be manageable with dose adjustment in selected adults at risk for neuropsychiatric effects.

Sawant AP, Shaw N, Clifton IJ et al. · Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · (2026) · View on PubMed ↗

Central Nervous System Effects of GLP-1 Receptor Agonists: A Systematic Review of Human Neuroimaging Studies.

This systematic review evaluated human neuroimaging studies to characterize central nervous system (CNS) effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs). The key finding was that GLP-1RA-related neural responsivity and its temporal dynamics vary across studies and are modulated by factors influencing CNS response. Scientifically, it consolidates current human evidence on how GLP-1RAs act in the brain, informing future mechanistic trials for psychiatric and neurodegenerative indications.

Brucar LR, Miller KB, Volkow ND · Neuroscience and biobehavioral reviews · (2026) · View on PubMed ↗

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Cardiovascular prevention and lipid disorders

Single-cell sequencing-guided discovery of narciclasine as a dual VCAM-1/ICAM-1 inhibitor for atherosclerosis management.

This study used human atherosclerosis single-cell RNA sequencing datasets to identify disease-driving genes and then applied connectivity map analysis, network pharmacology, and machine learning to discover narciclasine as a candidate therapy. It proposed narciclasine as a dual inhibitor of VCAM-1 and ICAM-1 and supported drug–target interactions using molecular docking and molecular dynamics simulations. The work suggests narciclasine could be developed to therapeutically modulate endothelial adhesion pathways involved in atherosclerosis.

Wang Y, Cao Z, Lan H et al. · Genes & diseases · (2027) · View on PubMed ↗ · Free PDF ↗

Real-world use of bempedoic acid for hypercholesterolaemia: a German multicentre, retrospective, cohort study.

This German retrospective multicenter cohort study evaluated real-world lipid-lowering effectiveness of bempedoic acid, an adenosine triphosphate citrate lyase (ACL) inhibitor, in patients with primary hypercholesterolaemia or mixed dyslipidaemia. The key finding (as assessed in the study) is the degree of LDL-C reduction achieved in routine care across centers compared with expected guideline targets. Clinically, the results will clarify how well bempedoic acid performs outside randomized trials and may identify gaps in implementation that affect cardiovascular risk reduction.

Haberbosch L, Baessler A, de Ruiter U et al. · Lipids in health and disease · (2026) · View on PubMed ↗ · Free PDF ↗

The Impact of Antihypertensive De-escalation: A Secondary Analysis of Systolic Blood Pressure Intervention Trial (SPRINT).

This secondary analysis studied whether antihypertensive de-escalation (reducing the number of medications and raising systolic blood pressure eligibility) affects major adverse cardiovascular events (MACE) in participants from the Systolic Blood Pressure Intervention Trial (SPRINT). De-escalation strategies that increased systolic blood pressure into an eligibility range were evaluated against intensive versus standard randomized targets to determine their association with cardiovascular outcomes. The analysis informs how safely clinicians might reduce antihypertensive intensity without increasing cardiovascular risk in high-risk patients.

Du F, Smith SM, Coulombe J et al. · High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · (2026) · View on PubMed ↗

Targeting Lipoprotein(a): A New Era in Cardiovascular Disease Prevention.

This review studied lipoprotein(a) [Lp(a)] as a genetically determined causal risk factor for atherosclerotic cardiovascular disease and calcific aortic stenosis, emphasizing its unique structure and enrichment with oxidized phospholipids. It finds that elevated Lp(a) contributes substantially to residual cardiovascular risk despite optimal control of traditional risk factors, and it summarizes guideline recommendations for at least one-time universal screening to guide personalized prevention. The significance is that Lp(a)-targeted risk stratification and emerging therapies may improve cardiovascular prevention beyond standard lipid management.

Bene-Alhasan Y, Nambi V, Abushamat LA et al. · Methodist DeBakey cardiovascular journal · (2026) · View on PubMed ↗ · Free PDF ↗

Familial Hypercholesterolemia.

This review studied familial hypercholesterolemia (FH), a semi-dominant autosomal monogenic disorder characterized by markedly elevated LDL cholesterol and premature ASCVD. It reports that the most common heterozygous FH is driven by pathogenic variants in the LDL receptor (LDLR) gene (with additional causes in APOB and PCSK9 and other rarer genes), and it provides prevalence estimates (~1 in 311). Clinically, the article underscores the genetic basis for diagnosis and risk assessment and supports targeted management strategies for early ASCVD prevention.

Iatan I, Genest J · Methodist DeBakey cardiovascular journal · (2026) · View on PubMed ↗ · Free PDF ↗

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Antiviral and infectious disease mechanisms

Regulatory roles of G-quadruplexes and G-quadruplex-binding proteins across the enhancer and promoter of the HBV genome.

This study investigated genome-wide regulatory roles of G-quadruplexes (G4) and G4-binding proteins (G4BPs) across the enhancer and promoter regions of the hepatitis B virus (HBV) genome. The key finding is that specific G4 structures and their binding proteins are positioned to modulate HBV regulatory elements, implying coordinated control of viral transcriptional regulation. This supports G4/G4BP biology as a potential targetable mechanism for antiviral therapy in HBV infection.

He L, Huang B, Ma H et al. · Virology journal · (2026) · View on PubMed ↗ · Free PDF ↗

Maternal RSV vaccination: clinical efficacy, safety, and global policy considerations: a systematic review.

This systematic review studied maternal RSV vaccination by assessing clinical efficacy and safety outcomes for newborns, using a PROSPERO-registered PRISMA-compliant search across multiple databases up to mid-2026. It reports that 16 publications (including real-world studies) informed a descriptive synthesis rather than a meta-analysis due to heterogeneity, summarizing efficacy and safety evidence across study designs. The significance is informing global policy decisions on whether and how maternal RSV vaccination should be implemented to protect infants during early life.

Hammour KA, Manaseer Q, Dweik M et al. · Journal of pharmaceutical policy and practice · (2026) · View on PubMed ↗ · Free PDF ↗

Fatal Persistent Cavitary Mycobacterium avium Complex Pulmonary Disease in a Non-HIV Patient With Prior Malignancy.

This case report studied a 71-year-old non-HIV woman with prior malignancy and recurrent Mycobacterium avium complex (MAC) pulmonary infection who developed fatal persistent cavitary MAC lung disease. It found that despite the typical chronic, slowly progressive course of MAC in non-HIV patients, this patient’s disease progressed to respiratory failure and death, highlighting cavitary disease and structural lung abnormalities as major risk factors for progression. The report is clinically significant because it underscores the need for aggressive monitoring and management of cavitary MAC in non-HIV patients with prior lung damage and incomplete treatment risk.

Ataya L, Beck G, Shamieh A · Cureus · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer immunotherapy, checkpoint biology, and T-cell states

Immune-pressure redistribution in resistance to PD-1/PD-L1 blockade: mechanisms, biomarkers, and therapeutic design.

This review synthesizes mechanisms of resistance to PD-1/PD-L1 blockade by proposing “immune-pressure redistribution” as a treatment-oriented framework. The key finding is that checkpoint release redirects immune pressure into three coupled resistance routes—tumor-intrinsic escape (including antigen-presentation loss and interferon-response defects), weakening via defective priming/terminal T-cell differentiation, and broader oncogenic/lineage adaptations—rather than isolated compartment-specific changes. The scientific significance is that this framework yields actionable biomarker concepts and therapeutic design principles to anticipate and counter coordinated resistance.

Wang X, Liu J, Hairulajiang A et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Strategies to prevent post-transplant relapse in acute myeloid leukemia and myelodysplastic syndromes.

This narrative review summarizes strategies to prevent post-transplant relapse in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after allogeneic hematopoietic stem cell transplantation. The key finding is that post-transplant interventions can be deployed as prophylactic maintenance (often in high-risk patients even without measurable residual disease) or as pre-emptive therapy triggered by measurable residual disease (MRD) or declining donor chimerism, with hypomethylating agents such as azacitidine highlighted as feasible options. Clinically, the review supports MRD- and risk-adapted post-transplant treatment strategies to reduce relapse while leveraging graft-versus-leukemia timing.

Najima Y · International journal of hematology · (2026) · View on PubMed ↗

TSPAN32 enhances CAR-T cell potency by assembling IL-2 receptor complex and amplifying its intracellular signal transduction.

This study assessed whether TSPAN32 expression enhances CD19 CAR-T cell potency and cytokine secretion in T cells from patients with B-cell lymphoma, using engineered CAR-T cells co-expressing TSPAN32 and CD19-CAR. The key finding is that TSPAN32 increases CAR-T antitumor activity by assembling the IL-2 receptor complex and amplifying downstream intracellular IL-2R signaling. This supports TSPAN32 as a potential engineering target to improve CAR-T efficacy in B-cell malignancies.

Sun Y, Qiu Q, Wang B et al. · British journal of cancer · (2026) · View on PubMed ↗

T-Cell Exhaustion and Senescence in Cancer: Regulatory Circuits and Therapeutic State Engineering.

This review synthesized evidence on how T-cell exhaustion and senescence arise in cancer through regulatory circuits involving transcriptional, epigenetic, signaling, and metabolic programs. The key finding is that T-cell states (naïve, activated, effector, memory, exhausted, senescent) form continuous, context-dependent trajectories rather than fixed subsets, shaped by tumor microenvironment cues. This framework supports “therapeutic state engineering” approaches to reprogram T cells toward more effective anti-tumor phenotypes for improved immunotherapy responses.

Han J, Lyu X, Wu M et al. · Cancer letters · (2026) · View on PubMed ↗

Tarlatamab in small cell lung cancer following platinum-based chemotherapy: subgroup analysis of Japanese patients from the DeLLphi-304 study.

This subgroup analysis evaluated efficacy and safety of tarlatamab versus amrubicin in Japanese patients with small cell lung cancer (SCLC) after platinum-based chemotherapy in the Phase 3 DeLLphi-304 trial. In the enrolled Japanese cohort (tarlatamab n=12; amrubicin n=23), tarlatamab demonstrated clinical benefit on overall survival with safety outcomes reported relative to amrubicin. The results extend the evidence base for tarlatamab’s post-platinum treatment role in a specific national population and support region-specific clinical decision-making.

Kurata T, Sugawara S, Akamatsu H et al. · International journal of clinical oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Beyond poly(ADP-ribose) polymerase inhibition: emerging therapeutic strategies for germline BRCA1/2-mutated and PALB2-mutated breast cancers.

This review studied emerging therapeutic strategies for breast cancers with germline or somatic biallelic inactivation of BRCA1, BRCA2, or PALB2, focusing on how to extend benefit beyond PARP inhibitor (PARPi) monotherapy. It highlights that although olaparib and talazoparib are approved for germline BRCA1/2-mutated breast cancer, resistance and toxicity limit durable responses, motivating exploration of novel vulnerabilities and combination approaches in homologous recombination deficiency (HRD). Clinically, the synthesis frames next-generation regimens to overcome PARPi resistance and reduce treatment-related harm in HRD-driven breast cancer.

Etessami JD, Tori L, Aconito M et al. · Current opinion in oncology · (2026) · View on PubMed ↗

Tamibarotene with venetoclax and azacitidine in RARA+ acute myeloid leukemia: results from the SY-1425-202 study.

This randomized multicenter SY-1425-202 study evaluated tamibarotene (an oral selective RARA agonist) combined with venetoclax and azacitidine versus venetoclax/azacitidine alone in newly diagnosed, unfit acute myeloid leukemia (AML) patients with RARA-positive disease. It found that adding tamibarotene to VEN/AZA was feasible to test in this RARA+ AML population and was assessed for safety and efficacy across study parts including post–VEN/AZA failure salvage. The results are significant because they target a defined molecular subtype (RARA overexpression) using a rational differentiation/combination strategy to potentially improve outcomes in unfit AML.

Cluzeau T, Borate U, McMahon C et al. · Blood neoplasia · (2026) · View on PubMed ↗ · Free PDF ↗

Immune checkpoint inhibitors plus chemotherapy for early-stage or locally -advanced triple-negative breast cancer: a systematic review and Bayesian network meta-analysis of randomized trials.

This systematic review and Bayesian network meta-analysis studied immune checkpoint inhibitor (ICI) plus chemotherapy regimens for early-stage or locally advanced triple-negative breast cancer (TNBC), comparing multiple PD-1/PD-L1 agents and treatment strategies (neoadjuvant-only versus perioperative “full-course”). It found relative efficacy and safety differences across the evaluated ICI-based regimens and overarching strategies using Bayesian NMA of randomized trials. The analysis is significant because it provides comparative guidance for selecting among specific ICI combinations and sequencing approaches in TNBC where head-to-head evidence is limited.

Leng Y, Dan J, Heng Q et al. · Frontiers in oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Co-stimulatory signal deficiency impairs cytotoxic T lymphocyte function in tumor immune evasion: molecular mechanisms and therapeutic implications.

This translational study analyzed how co-stimulatory signal deficiency drives tumor immune evasion by impairing cytotoxic T lymphocyte (CTL) function, focusing on the B7-1/B7-2–CD28 co-stimulatory axis and related checkpoint and tumor microenvironment mechanisms. The key finding is that when co-stimulation is weak or absent, tumor-reactive CD8+ T cells may fail to expand, survive, or maintain cytotoxic activity, enabling tumors to remodel the microenvironment and increase inhibitory signaling. Therapeutically, it highlights molecular mechanisms that could be targeted to restore effective CTL responses in cancer.

Ma J, Chen J, Miao T et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer metabolism, lipid biology, and metabolic reprogramming

Whole genome duplication through mitotic slippage causes nuclear instability.

This experimental study compared routes to whole-genome duplication (WGD) via mitotic slippage versus other non-canonical cell-cycle mechanisms under physiological and non-physiological conditions. The key finding is that only mitotic slippage produced widespread nuclear abnormalities termed “nuclear instability,” linked mechanistically to softer nuclei that are more vulnerable to microtubule-driven deformation. Scientifically, it shows that the pathway to polyploidy matters for genome/ nuclear integrity, informing how polyploidy may contribute to disease progression.

Gemble S, Budzyk M, Simon A et al. · The EMBO journal · (2026) · View on PubMed ↗ · Free PDF ↗

ADORA1 inhibition suppresses colon cancer development via hippo tumor suppressor pathway.

This study examined whether caffeine modulates adenosine receptor ADORA1 to suppress colon cancer development by regulating the Hippo/YAP tumor suppressor pathway in colon cancer models. The authors report that caffeine competitively blocked ADORA1 activation, leading to increased YAP phosphorylation/inactivation and reduced colon cancer carcinogenesis and progression. These findings suggest ADORA1–Hippo/YAP signaling as a mechanistic target through which caffeine may confer colon cancer protection and inform pathway-based therapeutic strategies.

Li Z, Liu Z, Zhang X et al. · Cell death and differentiation · (2026) · View on PubMed ↗

MAL2-Driven Lipid Droplets as Trojan Horses: Subverting Immune Surveillance to Promote Colorectal Cancer Liver Metastasis.

This study used single-cell RNA sequencing (scRNA-seq), transcriptomics, and mass cytometry (CyTOF) to identify MAL2-driven immune-metabolic mechanisms in colorectal cancer liver metastasis (CRLM). MAL2 was upregulated and enriched in malignant epithelial cells, where it activated non-canonical NF-κB (ncNF-κB) signaling to drive FASN transcription and promote lipid droplet formation that helps tumor cells evade immune surveillance. These results position MAL2–ncNF-κB–FASN lipid droplet biology as a targetable axis for limiting CRLM progression.

Dai S, Liu Z, Sun J et al. · Cancer letters · (2026) · View on PubMed ↗

Nucleolar METTL16 drives ccRCC tumorigenesis and pazopanib resistance via translational activation of JAG1/Notch signaling pathway.

This study investigated how the m6A methyltransferase METTL16 regulates clear cell renal cell carcinoma (ccRCC) tumorigenesis and resistance to the tyrosine kinase inhibitor pazopanib, using multi-omics integration plus in vitro and in vivo functional assays and clinical validation. METTL16 was upregulated and promoted pazopanib resistance by translationally activating JAG1/Notch signaling through its catalytically active m6A-writing activity. These findings identify METTL16–JAG1/Notch as a mechanistic driver of TKI resistance and support targeted small-molecule inhibition of METTL16 as a potential therapeutic strategy in advanced ccRCC.

Gong Z, Dong K, Chen W et al. · Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · (2026) · View on PubMed ↗

Schwann Cells in Physical Nerve Injury and Tumor Perineural Invasion: A Functional Overview and Comparison.

This article provided a functional overview comparing Schwann cell roles in peripheral nerve injury versus tumor contexts, focusing on how Schwann cell plasticity can be co-opted during cancer progression. It highlights that while Schwann cells promote peripheral nerve regeneration after injury, in tumors they can facilitate perineural invasion in a context-dependent manner. Scientifically, the review frames Schwann cells as potential targets for limiting perineural spread while preserving regenerative pathways.

Zheng Y, Chen X, Liu J et al. · Cancer medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Metabolic Reprogramming of Cancer Stem Cells: Targeting Lipid Flux and Mitochondrial Plasticity to Overcome Therapeutic Resistance.

This review synthesized evidence that cancer stem cells (CSCs) exhibit metabolic reprogramming driven by lipid flux and mitochondrial plasticity to survive therapy and drive relapse. It emphasizes that CSCs dynamically switch among glucose utilization, oxidative phosphorylation, redox control, fatty-acid synthesis, lipid uptake/sequestration, and fatty-acid oxidation in response to hypoxia, nutrient limitation, stromal cues, and therapeutic stress. The significance is that targeting lipid/mitochondrial metabolic flexibility may overcome therapeutic resistance in CSC-driven cancers.

Uti DE, Alum EU, Egbung JE et al. · Cancer medicine · (2026) · View on PubMed ↗ · Free PDF ↗

ZMIZ1 promotes aerobic glycolysis and development of hepatocellular carcinoma through inducing NOTCH1-mediated transcription of PYCR1.

This study investigated the role of ZMIZ1 in hepatocellular carcinoma (HCC) metabolism and tumor development, using public datasets, clinical specimens/tissue microarrays, and gain- and loss-of-function plus rescue experiments and xenograft models to define mechanism. The key finding was that ZMIZ1 promotes aerobic glycolysis and HCC progression by inducing NOTCH1-mediated transcription of the metabolic gene PYCR1. Clinically and scientifically, it identifies a ZMIZ1–NOTCH1–PYCR1 regulatory axis as a potential therapeutic target to disrupt glycolytic reprogramming in HCC.

He J, Zhang C, Chen G et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Dermatology: hidradenitis suppurativa and skin inflammation

TRPV1 channels in skin homeostasis and disease: From sensory transduction to therapeutic targeting.

This review summarizes how TRPV1 channels contribute to skin homeostasis and disease, spanning sensory transduction to therapeutic targeting. The key finding is that TRPV1 activation (by heat, acidic pH, capsaicin, and inflammatory mediators) drives Ca2+ influx and neurogenic inflammation, while also supporting physiological processes such as epidermal barrier repair, wound healing, and hair follicle biology. Scientifically, it frames TRPV1 as both a mechanistic driver of cutaneous inflammation/pruritus and a druggable target for skin disorders.

Song F, Xiang Y, Nie H et al. · International immunopharmacology · (2026) · View on PubMed ↗

CUDERMA project: Delphi consensus on quality indicators for certification of dermatology units providing care for hidradenitis suppurativa.

This Delphi consensus study aimed to define quality indicators for certification of dermatology units providing care for hidradenitis suppurativa (HS) using a literature review, focus groups of HS specialists, and a multidisciplinary expert panel. The key finding was the development and expert evaluation of a preliminary set of HS unit quality indicators to standardize clinical practice. Clinically, this supports scalable certification criteria that may improve consistency and quality of HS care across dermatology services.

Martorell A, García Martínez FJ, Molina Leyva A et al. · Actas dermo-sifiliograficas · (2026) · View on PubMed ↗ · Free PDF ↗

Association between COVID-19 and exacerbation of allergic skin diseases: A retrospective questionnaire-based cross-sectional study in Western China.

This retrospective questionnaire-based cross-sectional study assessed whether COVID-19 infection is associated with exacerbations of chronic allergic skin diseases—specifically atopic dermatitis (AD) and chronic urticaria (CU)—in patients attending a tertiary dermatology outpatient center in Western China. Participants reported changes in disease status within 14 days of COVID-19 symptom onset/diagnosis, alongside infection status, medication use, and clinical characteristics. The significance is that it provides real-world evidence on COVID-19 as a potential trigger for allergic skin disease flares, informing patient counseling and monitoring during infection waves.

Liu YL, Zhang ZY, Chen XM · Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration and lysosomal/vesicle dysfunction

TBK1 overexpression reduces neuronal loss in the P497S UBQLN2 mouse model of ALS/FTD.

This preclinical study tested whether TBK1 overexpression reduces neuronal loss in the P497S UBQLN2 mouse model of ALS/FTD. The authors report that TBK1 protein declines in end-stage P497S UBQLN2 mice and that increasing TBK1 expression via overexpression mitigates neuronal loss. These findings support TBK1 as a disease-relevant modifier and a potential therapeutic target for UBQLN2-linked ALS/FTD.

Wang S, Dolce MA, Burkett AM et al. · Neurobiology of disease · (2026) · View on PubMed ↗ · Free PDF ↗

Defective ATP13A2-ITCH-ALIX signaling impairs intraluminal vesicle biogenesis and increases neuronal vulnerability.

This study examined the role of ATP13A2-ITCH-ALIX signaling in lysosomal/exosome biology using ATP13A2-deficient human cell models. Defective ATP13A2-ITCH-ALIX signaling impaired intraluminal vesicle biogenesis and increased neuronal vulnerability. These findings connect a neurodegeneration-associated gene (ATP13A2) to vesicle/exosome pathway dysfunction, offering a mechanistic target for diseases such as early-onset Parkinsonism and related lysosomal disorders.

Luo L, Chen W, Luo S et al. · Cellular signalling · (2026) · View on PubMed ↗

Life at the interface: Byron Caughey’s search for prion disease inhibitors through chemistry, structure, and cell physiology.

This article reviewed Byron Caughey’s contributions to prion disease inhibitor discovery, focusing on the chemistry, structural biology, and cell physiology approaches used to target misfolded protein conformational changes. It highlights key techniques such as cell-free conversion assays to monitor protein misfolding in real time and the rationale for targeting conformational states rather than only native protein forms. The review is significant because it connects historical mechanistic drug-discovery strategies to ongoing therapeutic development for prion diseases and related neurodegenerative disorders.

Carroll JA, Soukup J, Groveman BR et al. · Acta neuropathologica · (2026) · View on PubMed ↗

Epilepsy with myoclonic-atonic seizures: a comprehensive review with emphasis on current and emerging pharmacotherapies.

This comprehensive review studied epilepsy with myoclonic-atonic seizures (EMAtS/Doose syndrome) by synthesizing the clinical spectrum, diagnostic approach, and the genetic landscape to contextualize current and emerging pharmacotherapies. It found that advances in genetic diagnostics and precision treatment approaches are reshaping management, with updated antiseizure treatment options discussed alongside emerging targeted strategies. The review is significant for clinicians because it consolidates evolving evidence to guide diagnosis and therapy selection in a developmental and epileptic encephalopathy with heterogeneous causes.

Samanta D · Expert review of neurotherapeutics · (2026) · View on PubMed ↗

The ageing microenvironment in sarcopenia: early alterations and targeted therapeutic strategies.

This review studied the ageing microenvironment in sarcopenia, focusing on early alterations that precede or drive loss of muscle mass and function. It finds that early dysregulation includes immune homeostasis changes, cellular senescence and senescence-associated secretory phenotype (SASP), satellite cell depletion/dysfunction, regenerative niche disruption, mitochondrial dysfunction, impaired proteostasis, and neuromuscular junction degeneration. The significance is that these early microenvironmental targets may enable more effective, targeted therapeutic strategies to prevent or slow sarcopenia progression.

Zhang L, Li G, Long L et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Metabolic switching in MASLD: therapeutic roles of ketogenic diet, intermittent fasting, and the gut-liver axis.

This narrative review studied metabolic switching in MASLD by evaluating ketogenic diet and intermittent fasting strategies and their relationship to the gut-liver axis. It finds that, depending on protocol (e.g., conventional/eucaloric ketogenic diet vs very-low-energy ketogenic therapy and distinct fasting regimens), these interventions can reduce body weight, improve insulin sensitivity, and decrease hepatic steatosis, but human evidence is often short-term and protocol-dependent. Clinically, it supports further development and careful selection of dietary/fasting protocols as potential metabolic therapies for MASLD, especially considering fibrosis stage as a key determinant of long-term risk.

Khanuja PK, Mohan V, Perez Martinez A et al. · Frontiers in nutrition · (2026) · View on PubMed ↗ · Free PDF ↗

Neuro-glial lipid imbalance in a Drosophila model of amyotrophic lateral sclerosis 8.

This study used a Drosophila model of amyotrophic lateral sclerosis 8 carrying the VAPBP58S (VAPB) missense mutation to examine neuro-glial lipid imbalance, focusing on membrane contact sites (MCS) regulated by the ER-resident tether protein VAPB. The key finding was that the ALS8-associated VAPB mutation produces dysregulated lipid homeostasis in the brain. Scientifically, it links VAPB/MCS dysfunction to lipid imbalance as a potential driver of neurodegeneration, providing a tractable in vivo model for testing lipid-targeted mechanisms.

Garg L, Chaplot K, Kuppili G et al. · Acta neuropathologica communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Anti-obesity and GLP-1–based therapies

Changes in Abdominal Adiposity and Associations With Metabolic Health Markers Following Tirzepatide in Japanese Participants With Obesity Disease: Results From the SURMOUNT-J Study.

This analysis from the randomized SURMOUNT-J trial evaluated changes in abdominal adiposity and metabolic health markers after tirzepatide in Japanese adults with obesity disease without diabetes. The key finding is that tirzepatide (10 or 15 mg) produced week-72 improvements in weight and abdominal fat compartments (visceral adipose tissue, subcutaneous adipose tissue, and hepatic fat fraction) that were associated with glycemic improvements, compared with placebo plus lifestyle modification. These data support abdominal fat reduction as a mechanistic contributor to tirzepatide’s metabolic benefits in Japanese patients with obesity.

Waki H, Kaneyuki E, Shingaki T et al. · Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · (2026) · View on PubMed ↗ · Free PDF ↗

Chronic low-grade inflammation drives skeletal aging and neurocognitive decline: inflammaging as a central hub coupling bone-brain aging.

This review studied how chronic low-grade sterile inflammation (“inflammaging”) driven by senescent cells and their senescence-associated secretory phenotype couples skeletal aging with neurocognitive decline in the context of age-related comorbidity between osteoporosis and cognitive impairment. It found that inflammaging acts as a central hub linking bone and brain aging through shared immunopathological pathways, including senescence-associated inflammatory signaling. The synthesis is clinically significant because it reframes osteoporosis–cognition comorbidity as a unified immunobiology problem that may enable cross-disciplinary prevention and targeted anti-senescence/anti-inflammatory strategies.

Yu M, Wu Y, Wang A et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Aesthetic Considerations for Preventing and Managing GLP-1 Receptor Agonist-Related Facial Aging.

This article studied how rapid or massive weight loss (MWL) after GLP-1 receptor agonist therapy affects facial adipose tissue and skin aging in patients treated for obesity or type 2 diabetes. It found that GLP-1 RA–associated MWL leads to facial adipose tissue depletion with skin laxity, volume loss, and accelerated aging—especially in periorbital and midfacial regions—while improved glycemic control may reduce advanced glycation end products and dampen inflammation. The findings are significant for clinical management because they provide aesthetic and preventive considerations to mitigate GLP-1 RA–related facial aging during weight-loss treatment.

Bommareddy K, Fabi S, Muniz M · The Journal of clinical and aesthetic dermatology · (2026) · View on PubMed ↗

CSF proteomic quantitative trait loci mapping reveals genetic insights into Alzheimer’s disease.

This study performed a genome-wide quantitative trait locus (pQTL) mapping analysis of cerebrospinal fluid (CSF) protein levels in 487 individuals using untargeted TMT mass spectrometry, with replication in the independent EMIF-AD MBD cohort (242 individuals), to identify genetic mechanisms underlying Alzheimer’s disease (AD). The authors report hundreds of independent CSF protein pQTL signals (399 independent signals mentioned in the abstract) that link genetic variation to specific protein abundance changes relevant to AD biology. These findings provide protein-level targets and pathway hypotheses for how AD risk variants may exert effects in the human brain via CSF proteome regulation.

Reus LM, Jiang C, Vilor-Tejedor N et al. · Molecular neurodegeneration advances · (2026) · View on PubMed ↗ · Free PDF ↗

Nobiletin ameliorates diabetic nephropathy by modulating TP53-associated PANoptosis: an experimental study.

This experimental study tested whether nobiletin (NOB) protects against diabetic nephropathy in 40 male db/db mice (with db/m controls) by examining TP53-associated PANoptosis and TFEB-related lysosomal and energy metabolic changes. Nobiletin treatment (30 or 60 mg/kg/day by gavage) was reported to ameliorate diabetic nephropathy through modulation of the TP53-linked PANoptosis program and related TFEB/lysosome and metabolic pathways. The results support nobiletin as a multi-pathway candidate for preventing or treating diabetic kidney injury by targeting coordinated cell-death and lysosomal-energy mechanisms.

Zhang B, Liu Y, Ma L et al. · Frontiers in nutrition · (2026) · View on PubMed ↗ · Free PDF ↗

Association of the dietary-behavioral risk index with metabolic syndrome and its components: a cross-sectional study in rural China.

This cross-sectional study assessed associations between an obesity-centered lifestyle score (OLS), the Diet Quality Index-International (DQI-I), and a newly constructed dietary-behavioral risk index (DBRI) with metabolic syndrome (MetS) and its components in 14,269 residents from rural Northwest China (CNC-NX cohort). The key finding was that DBRI (built using an Alkire-Foster dual cut-off approach and analyzed by quartiles) was associated with MetS and its components, indicating that combined dietary-behavioral risk correlates with cardiometabolic disease burden. These data help refine risk stratification in rural populations by integrating multidimensional diet and behavior into a single index linked to MetS.

Qiu J, Cui J, Chen K et al. · Frontiers in endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗

Herpes simplex virus 1 subverts the mitochondrial network to support the infection: A lesson on mitochondrial versatility.

This preprint investigated how herpes simplex virus 1 (HSV-1) remodels the mitochondrial network during infection, focusing on the viral UL12.5 gene and its effects on mitochondrial biogenesis and transcriptional control. The authors report that HSV-1 infection causes UL12.5-dependent inhibition of mitochondrial biogenesis via loss of mitochondrial DNA and reduced activity of PGC-1α and TFAM, while also describing UL12.5-independent mechanisms that further support infection. The work highlights mitochondrial versatility as a viral strategy and identifies UL12.5-linked host mitochondrial pathways as potential targets for antiviral intervention.

Saud R, Foster-Lemieur K, Duguay B et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗ · Free PDF ↗

α7nAChR alleviates cognitive impairment by promoting autophagy in astrocytes via CaMKK2/AMPK/mTOR pathway in sepsis-associated encephalopathy.

This study examined whether activating the α7 nicotinic acetylcholine receptor (α7nAChR) alleviates cognitive impairment in sepsis-associated encephalopathy (SAE) by promoting autophagy in astrocytes through the CaMKK2/AMPK/mTOR signaling pathway. Using a cecal ligation puncture (CLP) rat model and pharmacologic modulation with PNU282987 (activation) and methyllycaconitine (MLA; inhibition), the authors found that α7nAChR activation improved cognitive outcomes and increased astrocytic autophagy via the CaMKK2/AMPK/mTOR axis. These findings support α7nAChR–autophagy pathway modulation as a mechanistic therapeutic strategy for SAE-related brain dysfunction.

Liu Y, Wang F, Wang L et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Immunological dysregulation of follicular helper T cells, follicular regulatory T cells, and follicular cytotoxic T cells is associated with disease activity and identifies exploratory immune patterns in rheumatoid arthritis.

This study profiled circulating follicular helper T cells (Tfh), follicular regulatory T cells (Tfr), and follicular cytotoxic T cells (Tfc) in 41 rheumatoid arthritis (RA) patients and 16 healthy controls to determine links with disease activity and to identify immune patterns. The key finding was that immunological dysregulation of these follicular T-cell subsets—particularly involving Tfc—was associated with RA disease activity and enabled exploratory immune pattern identification. Clinically, this suggests peripheral follicular T-cell subset signatures could help characterize RA immunophenotypes and potentially guide targeted immunomodulatory strategies.

Fan Y, Li B, Wu R et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Generational safety profiles of BTK inhibitors: adverse reaction signals and real-world evidence from the FAERS database.

This pharmacovigilance study compared adverse event (AE) disproportionality reporting signals across four generations of Bruton’s tyrosine kinase (BTK) inhibitors—ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib—using the FAERS real-world evidence database. The authors’ key finding was that AE signal patterns differed among these BTK inhibitors, reflecting generation-dependent safety profiles and off-target or long-term risk characteristics. These results are significant for clinicians and regulators by informing risk-benefit decisions and post-marketing safety monitoring for BTK inhibitor selection.

Tu J, Wang Z, Zhang J et al. · Frontiers in medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Psychobiotic, nutritional, and behavioral interventions targeting the microbiome-gut-brain axis in depression, anxiety, and stress: a scoping review.

This scoping review mapped human intervention evidence targeting the microbiome-gut-brain axis (MGBA) for depression, anxiety, and stress, focusing on psychobiotic, nutritional, dietary, and behavioral strategies and how they relate to symptom and biomarker outcomes. The key finding was that evidence is fragmented across intervention types and biomarker domains, with limited integrative “symptom–biomarker bridging” across studies. Scientifically, the review identifies gaps and helps prioritize future trials that measure both clinical endpoints and mechanistic MGBA biomarkers.

Dai Q, Fang C, Du Y et al. · Frontiers in nutrition · (2026) · View on PubMed ↗ · Free PDF ↗

Safety and efficacy of low-density lipoprotein-lowering drugs in the elderly: a network meta-analysis of randomized controlled trials.

This network meta-analysis of randomized controlled trials evaluated the safety and efficacy of LDL-lowering drugs in elderly populations to compare multiple treatment strategies. The key finding was that different LDL-lowering therapies show varying balances of LDL reduction efficacy and safety outcomes in older adults, addressing concerns about statin tolerability and fatality risk. The results are clinically significant for selecting LDL-lowering regimens in elderly patients where both effectiveness and adverse-event risk must be considered.

Niaga KJK, Supinto PA, Tjandra KC et al. · Journal of geriatric cardiology : JGC · (2026) · View on PubMed ↗ · Free PDF ↗

Olfactory Tuft Cells Are Critical to Basal Inflammation, Innate Immune Response to Viral Infection, and Modulation of Quiescent Stem Cell Activation, Proliferation and Differentiation.

This study investigated the role of olfactory tuft cells in the olfactory mucosa, focusing on how they regulate basal inflammation, innate immune responses to viral infection, and quiescent stem cell activation, proliferation, and differentiation. Using genetic disruption of the Gng13 and Trpm5 gustatory signaling genes (encoding Gγ13 and TRPM5, respectively) and related mechanistic assays, the authors found that olfactory tuft cells are critical for coordinating immune defense and for modulating stem-cell behavior in the olfactory epithelium. These findings are significant because they link a specific sensory cell type to mucosal immunity and tissue regeneration, suggesting new targets for controlling inflammatory and infectious processes in the upper airway.

Zhang SS, Wang H, Yang YS et al. · Cell proliferation · (2026) · View on PubMed ↗ · Free PDF ↗

Orforglipron: An Oral GLP-1 Receptor Agonist for Obesity Treatment.

This review studied the newly approved oral GLP-1 receptor agonist orforglipron for obesity treatment, synthesizing evidence from phase 1 studies in healthy individuals and in patients with type 2 diabetes mellitus plus phase 2/3 obesity trials. The key finding is that orforglipron’s clinical development supports its efficacy and pharmacologic profile as an oral GLP-1 receptor agonist for obesity, based on the analyzed trial program. Clinically, this positions orforglipron as a potential oral alternative within GLP-1–based anti-obesity therapy, with implications for patient access and adherence.

Wietholter JP, Terpening CM · The Annals of pharmacotherapy · (2026) · View on PubMed ↗

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Circadian rhythms, energy sensing, and mitochondrial metabolism

The Circadian Clock Component NPAS2 is modulated by AMPK and Regulates Substrate Utilization and Mitochondrial Function in Human Skeletal Muscle Cells.

This study examined how AMP-activated protein kinase (AMPK) signaling regulates the circadian clock component NPAS2 and downstream metabolic programs in primary human skeletal muscle myotubes. AMPKα silencing altered core clock gene expression (including increased CRY1) and disrupted NPAS2/DBP-linked regulation of substrate utilization and mitochondrial function. These findings support a mechanistic link between energy sensing (AMPK) and circadian control of mitochondrial metabolism in human muscle, with implications for metabolic disease and chronotherapy strategies.

Rizo-Roca D, Pendergrast LA, Kamble P et al. · Molecular metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

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Gene therapy and genome editing (including CRISPR/AAV)

An evaluation of denecimig for bleeding prophylaxis in hemophilia A.

This article evaluated denecimig (Mim8), a fully human FVIIIa-mimetic bispecific antibody, for bleeding prophylaxis in people with hemophilia A, drawing on evidence from FRONTIER studies. The key finding is that denecimig is engineered for subcutaneous prophylaxis regardless of FVIII inhibitor status, with the review covering its molecular design, pharmacokinetics/pharmacodynamics, fixed-volume dosing, and efficacy/safety considerations. Scientifically and clinically, it positions denecimig as a next-generation prophylactic option aimed at reducing breakthrough bleeding and inhibitor-related limitations in hemophilia A.

Mahlangu JN · Expert opinion on biological therapy · (2026) · View on PubMed ↗

Development of CRISPR_SCD001, an Autologous Hematopoietic Stem Cell Gene Therapy for Sickle Cell Disease after CRISPR-Cas9 Mediated Correction.

This preclinical development study created CRISPR_SCD001, an autologous hematopoietic stem cell gene therapy that corrects the pathogenic HBB sickle allele using CRISPR-Cas9 homology-directed repair with a single-stranded oligodeoxyribonucleotide donor template. Using Plerixafor-mobilized peripheral-blood CD34+ cells, the authors reported ~22% mean HBB gene correction of alleles with ~51% allelic disruption and performed pharmacodynamic assessments, genotoxicity evaluation, and non-GLP toxicology in NBSGW mice. These data support the feasibility and safety evaluation of an HBB-targeted CRISPR approach for sickle cell disease using autologous CD34+ cells.

DeWitt M, Campo-Fernandez B, Roy S et al. · Molecular therapy : the journal of the American Society of Gene Therapy · (2026) · View on PubMed ↗

Targeting white matter astrocytes with a Gfap-disruptive Cas9 nuclease benefits a murine model of Alexander disease.

This study used an AAV-CRISPR/Cas9 strategy to disrupt Glial Fibrillary Acidic Protein (GFAP) in white matter astrocytes in a murine model of Alexander disease by delivering Cas9 under an astrocyte-specific promoter. A single neonatal intra-CSF injection of an all-in-one AAV-DJ8 vector expressing Staphylococcus aureus Cas9 achieved effective GFAP downregulation, aiming to correct astrocytic dysfunction and improve disease phenotypes. The work is significant because it demonstrates a targeted, cell-type-specific gene-editing approach (GFAP via Cas9) with therapeutic potential for Alexander disease.

Hillen AEJ, Capuano I, Gega B et al. · Molecular therapy : the journal of the American Society of Gene Therapy · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiac electrophysiology and calcium/lysosomal signaling

Lysosomal signaling pathways influence heart rhythm, and regulate atrial function.

This study investigated how lysosomal signaling via the NAADP pathway regulates heart rhythm and atrial function, using mouse and goat cardiac tissue and pharmacological or genetic ablation of the NAADP pathway in the sinoatrial node (SAN). The key finding was that disrupting NAADP/lysosomal Ca2+ signaling inhibits the SAN spontaneous beating rate response to β-adrenergic stimulation, and that lysosome–SR/mitochondria microdomains exist in mouse and goat tissue. Scientifically, it identifies lysosomal Ca2+ signaling as a regulator of pacemaker responsiveness, suggesting new mechanistic targets for atrial rhythm dysfunction.

Akerman E, Capel RA, Rog-Zielinska EA et al. · Cardiovascular research · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on September 21, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.