SEARCH · Search PubMed

Results for “disease”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources

PubMed2026

AI echo INSIGHT study: A prospective blinded randomized trial of artificial intelligence echocardiogram interpretation.

BACKGROUND: Transthoracic echocardiography (TTE) is the most commonly performed cardiac imaging modality with over 30 million studies annually. Demand for timely expert interpretation continues to outpace capacity, creating diagnostic delays and inter-observer variability that impact patient care. Recent research has suggested computer vision artificial intelligence (AI) models can generate accurate preliminary comprehensive TTE reports, however, prospective evaluation is needed to determine whether AI-assisted TTE interpretation can improve clinician efficiency while preserving diagnostic accuracy. METHODS: AI ECHO INSIGHT is a prospective randomized blinded clinical trial conducted at Kaiser Permanente Northern California that will evaluate 1200 historical TTE studies (1000 consecutive unselected studies plus 200 with moderate or greater valvular disease) interpreted using three workflows: (1) AI-generated preliminary report finalized by a blinded cardiologist (AI-assisted); (2) cardiologist-generated preliminary report finalized by a blinded cardiologist (cardiologist-assisted); and (3) sonographer-generated preliminary report finalized by a blinded cardiologist (sonographer-assisted). The primary outcome is the rate of substantial change between preliminary and final reports, comparing the AI-assisted workflow to the pooled cardiologist-assisted and sonographer-assisted workflows. Secondary outcomes include cardiologist interpretation time for report finalization, superiority testing for diagnostic accuracy, and reporting consistency. CONCLUSION: AI ECHO INSIGHT is a prospective randomized blinded clinical trial evaluating the clinical impact of AI-assisted TTE interpretation on diagnostic accuracy, cardiologist efficiency, and reporting consistency in real-world echocardiography workflows. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT07229300.

Humans↗

PubMed2026

TWIST2-dependent transcriptional activation of TPI1 mediates TGF-β1-driven fibroblast activation in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by aberrant profibrotic signaling and excessive extracellular matrix deposition, accompanied by fibroblast-to-myofibroblast transition. Despite extensive investigation, the molecular mechanisms underlying IPF pathogenesis remain incompletely understood. Here, we investigated the role of triosephosphate isomerase 1 (TPI1) in IPF progression and its regulation by transforming growth factor-β (TGF-β) signaling. Loss-of-function analyses identified TPI1 as a downstream effector of TGF-β1, as its knockdown markedly suppressed fibrotic marker expression, fibroblast proliferation, and migration. Mechanistically, TWIST2 was shown to function as a direct transcriptional regulator of TPI1, binding to its promoter and promoting transcriptional activation. Rescue experiments further confirmed that the TWIST2-TPI1 axis is central to the progression of pulmonary fibrosis. Notably, knockdown of either TPI1 or TWIST2 effectively attenuated TGF-β1-induced fibrotic phenotypes. Collectively, these findings define the TGF-β1/TWIST2/TPI1 signaling axis as an important regulator of pathogenic fibroblast behavior and pro-fibrotic responses through transcriptional control of TPI1, highlighting its potential as a therapeutic target for IPF.

Twist-Related Protein 1↗

PubMed2026

Integrated genomic and biochemical diagnosis of a novel homozygous start-loss variant in AKR1D1 associated with neonatal cholestasis.

INTRODUCTION: Congenital bile acid synthesis defects are rare autosomal recessive disorders that typically present in early infancy with cholestasis, progressive liver dysfunction, and, in severe cases, acute liver failure. These conditions may mimic other metabolic diseases detected in newborn screening, complicating early diagnosis. The AKR1D1 gene encodes Δ4-3-oxosteroid 5β-reductase, a key enzyme in primary bile acid synthesis, and pathogenic variants cause bile acid synthesis defect type 2 (OMIM #235555). CASE DESCRIPTION: We report a 3-month-old male infant with severe neonatal cholestasis and a history of elevated tyrosine levels in newborn screening. Pregnancy was high risk and unmonitored, with birth outside a hospital. Parental consanguinity was first-degree. Early metabolic evaluation showed transient normalization of tyrosine levels, but subsequent analyses revealed recurrent hyper-tyrosinemia. Urinary organic acids showed increased 4-hydroxyphenyl metabolites, with absent succinylacetone, excluding tyrosinemia type I. Progressive cholestasis developed, accompanied by coagulopathy, hyperbilirubinemia, hyperammonemia, and markedly elevated alpha-fetoprotein. Imaging revealed no structural liver abnormalities. Clinical exome sequencing identified a novel homozygous start-loss variant in AKR1D1, likely abolishing functional enzyme production. Metabolic studies confirmed increased urinary excretion of 3-oxocholenoic acids consistent with abnormal bile acid synthesis and supporting a diagnosis of bile acid synthesis defect type 2. Oral cholic acid therapy led to stabilization and improvement in clinical and biochemical parameters. DISCUSSION/CONCLUSION: This case illustrates the diagnostic complexity of neonatal cholestasis, particularly when initial metabolic findings suggest alternative etiologies. It highlights the importance of newborn screening as a tool for broader diagnostic suspicion and the critical role of early molecular diagnosis and multidisciplinary care. Timely recognition and targeted therapy can improve outcomes, prevent liver transplantation, and enable accurate genetic counseling, especially in consanguineous families.

Humans↗

PubMed2026

Barefoot ambulation following partial foot amputation: A systematic review of biomechanical outcomes.

BACKGROUND: Partial foot amputation (PFA) is increasingly performed due to rising prevalence of diabetes and peripheral vascular disease. While PFA may preserve gait and reduce energy expenditure compared with transtibial amputation, biomechanical deficits are common. This review aimed to evaluate biomechanical outcomes during baref following PFA. METHODS: A systematic review was conducted. MEDLINE, Embase, CINAHL, SCOPUS and Web of Science databases were searched for studies reporting biomechanical outcomes in adults with PFA without prosthesis. Eligible outcomes included spatiotemporal metrics, joint kinematics and kinetics, plantar pressures, and ground reaction forces. FINDINGS: Twelve studies including a total of 101 participants met inclusion criteria. Across studies, PFA was associated with impaired barefoot gait. This included spatiotemporal changes, such as reduced walking speed and shorter step length, and kinetic changes, such as reduced ankle power. Elevated plantar pressures were commonly reported, particularly in the forefoot and midfoot, highlighting loading abnormalities in the residuum. Several studies also described proximal compensatory strategies at the knee and hip, suggesting that biomechanical consequences extend beyond the foot and ankle. However, the evidence base was limited by small sample sizes, inconsistent protocols, and substantial heterogeneity. INTERPRETATION: Barefoot walking is impaired after partial foot amputation and the degree of dysfunction may vary by amputation level. Abnormal loading and compensatory changes may extend beyond the foot and ankle to the knee and hip. Given the limited and methodologically heterogeneous evidence, larger prospective studies with standardised biomechanical outcomes are needed to clarify the effects of amputation level and aetiology. This standardisation is important to inform surgical planning, rehabilitation, and prosthetic device design.

Humans↗

PubMed2026

A Phase I Study Assessing the Safety, Tolerability, and Pharmacokinetics of Yinfenidone: A Novel, Potent Drug for Idiopathic Pulmonary Fibrosis Treatment in Healthy Chinese Subjects.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a median survival of only 2-3 years after diagnosis. Yinfenidone (HEC585) possesses the potential to inhibit the proliferation of pulmonary fibroblasts, making it a promising candidate for the treatment of IPF. This study assessed the safety, tolerability, pharmacokinetics, and metabolic profile of Yinfenidone hydrochloride capsule in healthy Chinese subjects. METHODS: This single-center, randomized, double-blind, placebo-controlled, single ascending-dose trial included seven dose groups(20, 50, 100, 200, 400, 600, and 800 mg). Each group enrolled8 healthy subjects: 6 received Yinfenidone hydrochloride capsules and 2 received matching placebo under fasting conditions. Serial pharmacokinetic (PK) blood samples were collected pre-dose and post-dose, liquid chromatography-tandem mass spectrometry was used to analyze the plasma concentrations of Yinfenidone. Additionally, metabolic biotransformation of Yinfenidone in plasma were conducted in the 100 mg dose group. Safety and tolerability endpoints were monitored via physical examinations, vital signs measurements, clinical laboratory tests, 12-lead electrocardiography (ECG), and adverse events (AEs) documentation throughout the trial. FINDINGS: Yinfenidone was rapidly absorbed, with a median maximum plasma concentration (Tmax) of 1.8-3.0 hours, and had a mean half-life (t1/2) ranging from 31.9 to 62.0 hours. Within the 20-100 mg dose range, systemic drug exposure generally increased with ascending dose, above 100 mg, exposure increased less than proportionally to dose. Metabolite profiling in the 100 mg group revealed that the parentcompound predominated in plasma, with metabolic pathways including mono-oxygenation and N-dealkylation. All reported AEswere mild, classified as Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1. No serious AEs observed; no subject discontinued the trial due to AEs. Single oral doses of 20-800 mg Yinfenidone hydrochloride capsules administered under fasting conditions demonstrated favorable safety and tolerability profiles in healthy Chinese subjects. IMPLICATIONS: Yinfenidone exhibited rapid absorption (median Tmax, 1.8-3.0 hours) and a long terminal t1/2 ranging from 31.9 to 62.0 hours in this single ascending-dose study, indicating that Yinfenidone can be taken once a day in subsequent clinical studies. Yinfenidone mainly exists in human plasma as the original drug and is metabolized through a variety of metabolic pathways. The AEs observed with Yinfenidone in this study, such as diarrhea, nausea, and dizziness, were similar to those reported with pirfenidone. Overall, Yinfenidone demonstrated a favorable safety and tolerability profile in this cohort of healthy subjects.

Adult↗

PubMed2026

Reduced Length of ADT and ARTA With XRT in High-Risk Prostate Cancer (RELAX): A Randomised Controlled Trial.

AIM: To assess the efficacy of a short, intensified regimen of androgen deprivation therapy (ADT) and androgen receptor-targeted agent (ARTA) with curative-intent external beam radiotherapy (XRT) for high-risk prostate cancer (HRPCa) staged with prostate specific membrane antigen (PSMA) imaging. MATERIALS AND METHODS: The RELAX (Reduced Length of ADT and ARTA with XRT in high-risk prostate cancer) trial is a multicentre, phase II randomised non-inferiority trial comparing 9 months of ADT and 6 months of ARTA against the standard 24-month ADT, with definitive dose-escalated hypofractionated pelvic radiotherapy for PSMA-staged non-metastatic HRPCa. The primary endpoint is 5-year disease-free survival (DFS), defined from randomisation to first biochemical or clinico-radiological recurrence or any-cause death. Secondary endpoints include biochemical failure-free survival, metastasis-free survival, overall survival, testosterone recovery, treatment-related adverse effects, and patient-reported outcomes. Participants are monitored with serial serum PSA and testosterone levels, CTCAE and PRO-CTCAE assessments, and PSMA-PETCT at recurrence. The non-inferiority margin is set at 10% absolute difference from an expected 5-year DFS of 85% in the standard arm, with intention-to-treat analysis. The trial is ethics board approved and funded by institutional intramural grant, and registered on clinicaltrials.gov (NCT06818682). RESULTS: The planned accrual of 206 participants commenced in February 2025, with nearly a third of enrolment completed till date. CONCLUSION: The RELAX trial incorporates contemporary standards of PSMA-based staging, dose-escalated hypofractionated radiotherapy, and ARTA for HRPCa. The results are expected to inform the efficacy of a shorter, intensified androgen suppression strategy against the prevailing standard of long-term ADT for these patients.

Humans↗

PubMed2026

Meta-PseU: A meta-classifier for robust prediction of RNA pseudouridine modification sites from long sequences.

BACKGROUND AND OBJECTIVES: Pseudouridine (Ψ) represents one of the most abundant and conserved RNA modifications. Ψ provides an additional hydrogen-bond donor that enhances RNA structural stability and modulates translation. It participates in diverse biological processes, including RNA-protein interactions, splicing, translational control, and stress responses. Aberrant pseudouridylation is implicated in cancer, neurodegenerative disorders, and autoimmune diseases. Despite its biological importance, experimental identification of Ψ sites remains time-consuming and costly, limiting the feasibility of transcriptome-wide profiling. Computational approaches have therefore become essential complements to experimental techniques. However, state-of-the-art machine-learning and deep-learning predictors often suffer from limited generalizability due to small training datasets. To overcome these issues, we aim at constructing new long-sequence datasets and developing a novel Ψ site predictor. METHODS: New long-sequence datasets were constructed as benchmarks for RNA Ψ-site prediction. The Ψ modification sites in RMBase 3.0 were mapped to the reference genomes across three species of human, mouse, and yeast, and the RNA sequences with a length of 201 were generated by extending the upstream and downstream from the mapped, central sites. To eliminate sequence redundancy, the sequences were clustered using CD-HIT with a 70% sequence identity threshold. We developed Meta-PseU, a logistic regression-based meta-classifier that considered 118 machine learning and deep learning classifiers. The datasets and programs are freely accessible at https://github.com/kuratahiroyuki/MetaPseU. RESULTS: By optimizing model configuration, we proposed the Meta-PseU model stacking 32 machine learning and deep learning classifiers out of 118 classifiers. Meta-PseU substantially improved model generalizability, overcoming a key limitation of existing approaches. It greatly outperformed state-of-the-art predictors and achieved increasing accuracy with increasing sequence length. CONCLUSIONS: Long-sequence datasets were newly constructed as benchmarks for RNA Ψ-site prediction. Meta-PseU offers a new framework for robust Ψ-site identification by using long sequences.

Pseudouridine↗

PubMed2026

Clinical pharmacokinetics of afatinib: A systematic review.

BACKGROUND: Afatinib is commonly used in the treatment of non-small cell lung cancer (NSCLC). This systematic review summarizes clinical pharmacokinetics (PK) evidence focusing on the effect of disease state and drug interactions on afatinib exposure. METHODS: Google Scholar, Science Direct, PubMed, and the Cochrane library were searched for human studies reporting the clinical PK of afatinib. The search yielded 24 articles that met the predefined inclusion criteria. RESULTS: Afatinib exposure increased slightly more than dose proportionally, with higher doses producing greater AUC0-24 and Cmax values. The apparent oral clearance reported after administration of the oral solution was lower than that observed following tablet administration. The Cmax of afatinib increases by 38.5% after coadministration with ritonavir and exposure decreases 34.3% with rifampicin. The Cmax decreases 31.45% when given with pemetrexed. Both the AUC0-24 and Cmax increase in NSCLC and tumor state. The AUC0-24 of afatinib is 2.61 folds higher following multiple oral doses among patients with solid tumors. Afatinib exposure is 22.1 % higher in renal impaired patients than in healthy controls. In grade 2 diarrhea, the AUC0-24 of afatinib is 83.93% higher as than in grade 0-1 diarrhea in solid tumor patients. CONCLUSION: This systematic review provides an updated synthesis of clinical PK evidence on afatinib. Afatinib exposure is influenced by dose, repeated administration, renal impairment, diarrhea associated toxicity, and P-glycoprotein mediated drug interactions. These findings may support individualized dosing, toxicity-guided dose adjustment, and future development of PK models for afatinib.

Humans↗

PubMed2026

Targeting ncRNA control networks with engineered exosomes to overcome therapy resistance in thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent endocrine malignancy, accounting for over 90% of thyroid cancers. While differentiated thyroid cancers (DTCs) typically have favorable outcomes, a significant subset progresses to radioactive iodine-refractory (RAIR) disease, characterized by impaired iodine uptake and a 10-year survival rate below 10%. Genetic alterations and dysregulated signaling pathways underlie this transition. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), play critical regulatory roles in tumor biology and may be transported via exosomes, facilitating intercellular communication and contributing to RAIR-PTC. This systematic review, conducted according to PRISMA 2020 guidelines, evaluated the role of exosomal ncRNAs in RAIR-PTC. A comprehensive search of PubMed, PubMed Central, and Google Scholar identified studies published within the past 15 years in English. Following stringent quality appraisal, studies with a non-bias score above 40% were included. Of 961 identified publications, 96 high-quality studies met inclusion criteria. Evidence indicates that therapy resistance in RAIR-PTC is driven by convergent ncRNA regulatory networks that suppress sodium-iodide symporter (NIS) expression and activate oncogenic pathways, most notably MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. Multiple ncRNAs converge on key regulatory nodes, forming redundant circuits that sustain dedifferentiation, metabolic adaptation, and impaired iodide transport. Several consistently dysregulated ncRNAs directly or indirectly regulate NIS expression and trafficking, highlighting actionable targets. Exosomes emerge as biologically compatible, programmable delivery vehicles capable of transporting therapeutic ncRNA payloads independent of endogenous packaging mechanisms. These findings support a precision therapeutic paradigm in which engineered exosomes reprogram ncRNA networks to restore iodine-handling pathways and overcome therapy resistance in RAIR-PTC.

Humans↗

PubMed2026

Variations in the viral hepatitis C prevalence and treatment status by material hardship and cumulative risk among people who inject drugs.

People who inject drugs (PWID) are disproportionately impacted by viral hepatitis C (HCV). Among PWID, homelessness, poverty, and material insecurity elevate infectious disease risk. We hypothesized a positive association between material hardship (difficulty accessing basic needs) and lifetime diagnosis of HCV, and a negative association between cumulative risk (material hardship and years since first injection) and HCV treatment. From 2021-22, we conducted a survey among community-recruited PWID that included items on HCV outcomes, material hardship (a sum score of usually (4) to never (1) having difficulty finding food, clothing, shelter, restrooms, and showers in the past 3 months), and years since injection drug use initiation. We developed a latent variable, cumulative risk, by combining individual scores of material hardship indicators and years since first injection drug use. Among our sample of PWID (n = 471), 246 (53%) participants reported lifetime HCV diagnosis and 27% of those who tested positive for HCV reported ever or current treatment (n = 67). In modified-Poisson regression, a one-unit increase in material hardship score was associated with a 3% (OR: 1.03, 95% CI: 1.01%, 1.05%) increase in odds of HCV diagnosis. In latent modeling, among PWID testing positive for HCV, a one-unit increase in cumulative risk score was associated with a 0.28 (OR: -0.28, 95% CI: -0.50, -0.06), decrease in the Z-score odds of receiving HCV treatment. Findings emphasize structural interventions to strengthen material security and co-delivering basic needs with health services to improve HCV-related outcomes among PWID.

HCV↗

PubMed2026

Effect of renin-angiotensin system inhibitors on survival in glioma patients: A systematic review and meta-analysis.

PURPOSE: To evaluate the effect of renin-angiotensin system inhibitors (RASIs) on the survival outcomes of glioma patients, determine whether using RASIs correlates with survival benefit, and provide evidence-based guidance for the clinical treatment. METHODS: Studies assessing the effects of using RASIs versus non-use in glioma patients were retrieved from the PubMed, Cochrane Library, Web of Science, and Embase databases from inception to April 17, 2024. The included studies reported hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS), as well as the effect on brain edema and steroid dosing in patients. RESULTS: Seven articles involving 2660 patients were included in this study. Pooled results indicated there was no significant difference in OS (HR = 0.89, 95% CI 0.75-1.06, P = 0.204) or PFS (HR = 0.98, 95% CI 0.82-1.18, P = 0.847) between RASIs-treated patients and non-RASIs-treated patients. Sensitivity analysis identified the ACEIs-focused trial reported by Happold et al. as a major contributor to inter-study heterogeneity. Subgroup analyses revealed that in recurrent glioblastoma, pooled OS was significantly longer in RASIs-treated patients than non-RASIs-treated patients (HR = 0.70, 95% CI 0.54-0.92, P = 0.01). Similarly, compared with bevacizumab monotherapy, bevacizumab combined with RASIs significantly extended OS in glioblastoma patients (HR = 0.73, 95% CI 0.63-0.86, P < 0.001). CONCLUSION: The results revealed that treatment with RASIs may show a trend toward prolonged overall survival (OS) in patients with glioma. For patients with glioblastoma, RASI therapy could prolong OS in those with recurrent disease. Furthermore, compared with bevacizumab monotherapy, the combination of RASIs and bevacizumab was associated with improved OS in glioblastoma patients.

Humans↗

PubMed2026

Non-tobacco nicotine dependence and postoperative complications after total ankle arthroplasty: A propensity-matched cohort study.

BACKGROUND: The clinical impact of non-tobacco nicotine dependence (NTND) is poorly defined. This study evaluated the association between NTND and complications following total ankle arthroplasty (TAA). METHODS: A retrospective cohort study using the TriNetX Research Network was performed. Adults undergoing primary TAA (Current Procedural Terminology [CPT] 27702) between 2010 and 2025 were included. Patients were categorized into NTND (International Classification of Diseases, Tenth Revision [ICD-10]: F17, excluding tobacco-specific codes) and nonsmoker cohorts. Propensity score matching (1:1) yielded 939 NTND patients and 939 controls. Ninety-day medical and wound complications and ≥ 2-year mechanical outcomes were assessed. RESULTS: NTND patients had higher rates of 90-day readmission (11.7% vs 6.5%; OR 1.9), wound disruption (4.3% vs 2.6%; OR 1.7), surgical site infection (3.1% vs 1.6%; OR 2.0), and sepsis (2.4% vs 1.1%; OR 2.3). At a minimum 2-year follow-up, NTND was not associated with increased risk of mechanical complications. CONCLUSION: These findings challenge the assumption that smokeless nicotine products are benign in the perioperative setting and support incorporating NTND screening and cessation counseling into preoperative optimization protocols. Future prospective studies are warranted to further characterize the dose-dependent effects of non-tobacco nicotine exposure and to evaluate the impact of perioperative cessation strategies on outcomes following TAA. LEVEL OF EVIDENCE: IV.

Humans↗

PubMed2026

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P < 0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-κB-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-κB-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals↗

PubMed2026

Food-derived extracellular vesicles as delivery platforms for medicine-food homology components in metabolic syndrome.

Diet-induced obesity and associated metabolic syndromes have become major global public health challenge, highlighting the urgent need for safe and effective strategies. Recently, food-derived extracellular vesicles (FDEVs) have garnered increasing attention as natural nanocarriers due to their excellent biocompatibility and specific targeted delivery capabilities. FDEVs can efficiently deliver medicine-food homology components (MFHCs) to precisely regulate lipid metabolism, inflammatory responses, and insulin sensitivity, thereby improving obesity and its metabolic abnormalities. This systematic review summarizes recent advances in the use of FDEVs as delivery vehicles for MFHCs to suppress diet-induced obesity and metabolic syndrome, with a particular focus on the underlying molecular mechanisms, including signaling pathway regulation and cellular metabolic remodeling. In addition, the clinical translational potential and industrial application prospects of FDEVs are evaluated, and key challenges related to preparation techniques, safety assessment, and large-scale production are discussed. By integrating current evidence, this review aims to provide theoretical framework and future perspectives for the development of FDEVs as a novel targeted delivery platform and treatment of metabolic diseases.

Extracellular Vesicles↗

PubMed2026

Targeted Nrf2 activation improves vascular endothelial function with aging and prevents vascular dysfunction following disuse in younger and older adults.

Aging and physical inactivity/disuse contribute to cardiovascular disease, which is attributable, in part, to vascular endothelial dysfunction associated with impaired nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling. However, the ability to augment Nrf2 activation and its effects on age- and disuse-related vascular dysfunction in humans remains limited. In a double-blind, randomized, placebo-controlled study design 20 younger adults (8M/12F, age 27 ± 7 y) and 24 older adults (12M/12F, age 67 ± 8 y) were randomized to receive either placebo or PB125 (200 mg/day, Nrf2 activator) across three visits: baseline, 2 weeks of supplementation, and following either 5 days of bed rest (old) or 2 weeks of limb immobilization (young). Brachial and popliteal artery flow-mediated dilation (FMD), passive leg movement-induced (PLM) leg blood flow (LBF) and vascular conductance (LVC) and serum antioxidant status (superoxide dismutase, SOD) were assessed at each timepoint. Compared to placebo, 2 weeks of PB125 increased brachial (PB125: 2.8 ± 1.5 to 3.8 ± 1.3%, p < 0.0001) and popliteal FMD (PB125: 1.5 ± 1.5 to 2.3 ± 1.4%, p = 0.033) in older, but not younger adults (both, p > 0.27). During bed rest, PB125 preserved brachial (3.8 ± 1.3 to 3.6 ± 1.4%, p = 0.543) and popliteal FMD (2.3 ± 1.4 to 2.7 ± 1.4%, p = 0.269), LVC (1.1 ± 0.8 to 1.1 ± 1.5 AUC, p = 0.530) and circulating SOD concentrations (28.3 ± 7.2 to 28.6 ± 8.6 U/mL, p = 0.888) in older adults compared to placebo (all, p < 0.05). Following limb immobilization, PB125 preserved popliteal FMD (4.4 ± 2.8 to 3.4 ± 1.8%, p = 0.302) in younger adults compared to placebo (p < 0.05). These findings demonstrate targeted Nrf2 activation with PB125 improves age-related vascular endothelial dysfunction while preserving vascular function and antioxidant capacity following periods of disuse.

Humans↗

PubMed2026

An oxidative stress - and immunotherapy-related six-gene signature defines immune subtypes and predicts prognosis and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Oxidative stress and the tumor immune microenvironment jointly shape hepatocellular carcinoma (HCC) progression and response to immunotherapy, yet integrated biomarkers linking these processes are lacking. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify oxidative stress- and immunotherapyrelated differentially expressed genes (OSIRDEGs). Functional enrichment, weighted gene co-expression network analysis (WGCNA) and LASSO-Cox regression were used to construct a prognostic signature. Consensus clustering, TIDE, CIBERSORT and ssGSEA characterized immune phenotypes. Somatic mutation, copy-number and drug-response data were integrated to assess genomic alterations and drug sensitivity. Expression of model genes was validated by qRT-PCR and western blotting in HCC cell lines. RESULTS: We identified 24 OSIRDEGs enriched in cell-cycle and mitotic pathways. WGCNA intersection yielded 18 module genes, from which a six-gene signature (BUB1B, CDKN2A, CENPE, HMMR, PTTG1, SPP1) was derived. The signature robustly stratified patients into high- and low-risk groups with significantly different progression-free and disease-free survival in both TCGA-LIHC and GSE14520. Based on signature expression, two molecular subtypes were defined, exhibiting distinct survival, immune landscapes and predicted immunotherapy responsiveness. Model genes harbored recurrent alterations and showed significant correlations with anticancer agents. All six genes were upregulated at mRNA and protein levels in metastatic HCC cell lines versus normal hepatocytes. CONCLUSIONS: We systematically explored the landscape of OSIRDEGs in HCC, and proposed a validated six-gene signature that refines prognostic stratification, delineates immunerelevant HCC subtypes and highlights candidate biomarkers for therapeutic selection and mechanistic investigation.

Humans↗

PubMed2026

The feasibility and efficacy of weighted blankets as a sleep intervention for people with behavioural and psychological symptoms of dementia: a pilot randomised crossover trial.

Sleep disturbances contribute to disease progression in dementia and result in reduced quality of life. Non-pharmacological interventions are recommended for the management of sleep and other behavioural and psychological symptoms of dementia (BPSD), although these interventions can be challenging to implement. This pilot study assessed the feasibility and efficacy of weighted blankets as a sleep intervention for people with BPSD in a neurobehavioural unit. Fourteen residents, serving as their own control, slept two weeks with a weighted blanket and two weeks with usual bedding in a crossover trial. The primary outcomes were sleep duration and efficiency, measured via a Withing's sleep analyser and sleep disordered behaviours, measured by the sleep disorder inventory (SDI). Secondary outcomes included responsive behaviours, measured by the Neuropsychiatric index (NPI), falls incidents, restrictive practice incidents and use of pro re nata psychotropic medications. Generalised Estimation Equation (GEE) method was used for analysis. There was no statistical evidence that weighted blankets improved sleep or behavioural outcomes for people with BPSD, however fewer fall incidents, wakings and restrictive practices were reported during weighted blanket use. Weighted blankets were considered feasible and acceptable with high recruitment rates, nil participant withdrawals and no adverse outcomes, however there was variable compliance to the intervention protocol and the Withings did not adequately measure sleep. Whilst there is insufficient effectiveness evidence for further trials, weighted blankets can be offered to people living with dementia as a low risk sleep intervention option, with the caveat that there is currently no effectiveness evidence.

Behavioural Symptoms↗

PubMed2026

Precision Oncology in Hepatopancreatobiliary Cancer Surgery.

Advances in technology have allowed for the characterization of tumors at the genomic, transcriptomic, and proteomic levels. There are well-established targets for biliary tract cancers, with exciting new targets emerging in pancreatic ductal adenocarcinoma and potential targets in hepatocellular carcinoma. Taken together, these data suggest an important role for molecular profiling for personalizing cancer therapy in advanced disease and need for design of novel neoadjuvant studies to leverage these novel therapeutics perioperatively in the surgical patient.

Humans↗