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PubMed2026

A validated sensitive LC-MS/MS method and its application in elucidating the unique ocular pharmacokinetic profile of 0.01% atropine underpinning its clinical utility for myopia.

A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify atropine in ten rabbit ocular tissues enabling systematic characterization of the ocular pharmacokinetic profile of 0.01% atropine sulfate eye drops after a single topical administration. The method demonstrated excellent linearity (coefficient of determination, R2 ≥ 0.9908) across all matrices, with lower limits of quantification (LLOQ) of 0.05 ng/mL for most tissues and 0.10 ng/mL for retina and lens; intra- and inter-day accuracy, precision, matrix effects, extraction recoveries, and stability all met the acceptance criteria. Following a single bilateral topical dose (50 μL/eye) in New Zealand White rabbits, atropine distributed rapidly into all 12 ocular compartments (the sclera further divided into three anatomical regions) with marked heterogeneity-the highest exposures were found in conjunctiva and cornea, a distinct anterior-to-posterior concentration gradient was observed in the sclera, sustained retention was noted in the retina (mean residence time from zero to the last measurable time point, MRT0-t 3.30 h), while aqueous and vitreous humor eliminated rapidly (elimination half-life, t₁/₂ < 0.7 h), and all tissues except aqueous humor followed a two-compartment model. This validated method and the comprehensive pharmacokinetic data reveal that topically applied 0.01% atropine achieves sustained exposure in key myopia-regulating tissues (retina, choroid, posterior sclera) with low exposure in side-effect target tissues (iris, ciliary body, lens).

Animals↗

PubMed2026

Proteomic insights into hepatic responses to high soybean meal inclusion with citric acid supplementation in hybrid grouper (Epinephelus fuscoguttatus × Epinephelus lanceolatus) juveniles.

This study evaluated the growth performance and hepatic proteomic responses of juvenile hybrid grouper (Epinephelus fuscoguttatus × Epinephelus lanceolatus) juveniles fed diets containing 30% or 40% soybean meal (SBM), with or without 3% citric acid supplementation, and compared with a fishmeal (FM) control diet over a 10-week feeding trial. Fish fed 30% SBM (LSBM) showed a final body weight comparable to the FM group, whereas fish fed 40% SBM (HSBM) recorded significantly reduced growth and net protein utilization (NPU) (p < 0.05). Supplementation of citric acid in the 40% SBM diet (HSBM + CA) significantly improved NPU and partially restored growth relative to HSBM. LC-MS/MS based quantitative proteomics identified 1544 hepatic proteins and showed clear dietary segregation. Differentially expressed proteins were predominantly associated with reduced abundance of proteins involved in lipid metabolism, amino acid metabolism, pyruvate metabolism, and the tricarboxylic cycle across all SBM diets, suggesting a shift in oxidative metabolic capacity. In contrast, LSBM induced upregulation of spliceosome-associated proteins and RNA processing components, suggesting adaptive post-transcriptional regulation under moderate SBM inclusion. In contrast, HSBM exhibited greater reduction in metabolic protein abundance without comparable upregulation of adaptive regulatory components, coinciding with reduced nutrient retention. Protein-protein interaction analysis further confirms the correlation between the regulation of spliceosomal clusters and mitochondrial lipid-catabolic modules. Citric acid supplementation did not markedly reverse hepatic metabolic protein changes but improved protein retention. Data are available via ProteomeXchange with identifier PXD081994. These findings suggest a tolerance limit between 30% and 40% SBM inclusion, with 30% inducing adaptive hepatic proteomic responses compatible with maintained growth performance.

Animals↗

PubMed2026

Interface-dependent V. parahaemolyticus biofilm under varying temperatures, media, and oxygen conditions: implications for seafood safety.

Vibrio parahaemolyticus biofilms play a critical role in pathogen persistence in marine and seafood-processing environments, where oxygen availability, temperature, and surface interfaces vary widely. This study investigated biofilm development by three strains on partially submerged stainless-steel coupons under gas-liquid-wall (GLW) and fully submerged (SM) interfaces. Viable cell counts (log₁₀CFU/cm2) along with normalized protein concentration per viable cell (nProt) and normalized polysaccharide concentration per viable cell (nPol) were measured, under aerobic and anaerobic conditions across a temperature range of 15-30 °C, using tryptic soy broth with 3% NaCl (TSB) and seawater-based medium (SW). GLW biofilms consistently exhibited higher cell counts (6.4-7.3 log₁₀CFU/cm2) compared to SM biofilms (5.9-6.3 log₁₀CFU/cm2), suggesting that enhanced oxygen diffusion promotes bacterial proliferation. Conversely, SM biofilms exhibited significantly higher nProt and nPol levels (p < 0.001), indicating increased production of the extracellular polymeric substance (EPS) matrix under low-oxygen, high-nutrient conditions. Microscopy and three-dimensional surface plot analyses revealed relatively uniform biofilm layers at the GLW interface, whereas SM biofilms formed heterogeneous, tower-like structures. EPS production was further influenced by medium composition, oxygen, and temperature. SM biofilms grown in SW exhibited significantly higher nProt and nPol than those in TSB under aerobic conditions (p < 0.001), indicating enhanced matrix stabilization. Under anaerobic conditions at 15 °C, nProt and nPol were higher, whereas under aerobic conditions, peak nProt and nPol occurred at elevated temperatures. These findings highlight a trade-off between bacterial growth and matrix production and provide insight into biofilm adaptation and persistence in seafood-processing environments. These insights may help develop improved biofilm control and seafood safety management.

Biofilms↗

PubMed2026

Development and validation of an LC-MS/MS method for the quantification of the KRASG12C inhibitor divarasib.

Divarasib is a newly developed covalent KRASG12C inhibitor, currently under clinical investigation in a phase 3 trial in patients with non-small cell lung cancer (NSCLC). At the moment, very limited pharmacokinetic data are publicly known. However, obtaining more insight into the pharmacokinetic properties of divarasib is important, since this may provide a better understanding of its efficacy and safety risks. Pre-clinical studies have been performed in mouse models to evaluate the effect of drug transporters and drug-metabolizing enzymes on the plasma exposure and tissue distribution of divarasib. Therefore, a reliable quantification method is required. To our knowledge, no bioanalytical assay of divarasib has been published yet. Therefore, in this study we developed and validated an assay to quantify divarasib in human plasma and in eight different mouse-related matrices, and partially in mouse plasma, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was initially evaluated over a concentration range of 1-10,000 nM. However, due to carry-over observed at 10,000 nM, the validated calibration range was established at 1-2000 nM, with matrix-dependent LLOQs of 1-10 nM. Erlotinib was used as an internal standard and acetonitrile was utilized to perform protein precipitation as sample pretreatment. Divarasib demonstrated stability in human plasma and in mouse plasma and tissue homogenates under various experimental conditions. A pilot in vivo study showed the applicability of our validated LC-MS/MS method. Ongoing clinical trials may collect plasma samples, and this developed method enables quantification of divarasib in both mouse and human plasma samples.

Animals↗

PubMed2026

Discovery of NAT-6-321056 as a novel modulator of VEGFR2 signaling to suppress tumor angiogenesis.

Vascular endothelial growth factor receptor 2 (VEGFR2) is a master regulator of angiogenesis and cancer progression. However, current VEGFR2 modulators face significant challenges, including off-target toxicity and acquired resistance, underscoring the urgent need for novel therapeutic agents with improved efficacy and safety profiles. Here, we reported that virtual screening of 39,442 natural products from the ZINC natural products-derived library, coupled with molecular docking and molecular dynamics (MD) simulations to evaluate the binding stability of candidate compounds, identified NAT-6-321056 as a highly promising modulator of VEGFR2 signaling. Biological evaluations demonstrated that NAT-6-321056 exerted potent inhibition on the growth of a broad spectrum of cancer cells, including both solid tumors and hematological malignancies. In EA.hy 926 endothelial cells and SK-N-DZ neuroblast cells, the compound significantly suppressed proliferation, migration, and invasion. Microscale thermophoresis (MST) confirmed direct binding of NAT-6-321056 to VEGFR2 with favorable affinity. Kinase profiling against a panel of 33 kinases indicated that NAT-6-321056 exhibited a multi-kinase modulation profile. Mechanistic studies revealed that NAT-6-321056 suppressed the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and was associated with reduced VEGFR2 phosphorylation and attenuation of the downstream ERK/JNK/AKT signaling pathways. Moreover, NAT-6-321056 exhibited robust in vivo anti-angiogenic effects in both the chick chorioallantoic membrane (CAM) assay and transgenic zebrafish vascular fluorescence imaging models. Computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction suggested acceptable drug-like properties. Collectively, these findings demonstrated that NAT-6-321056 is a promising modulator of VEGFR2 signaling with potent anti-angiogenic activity and represents a viable candidate for cancer therapy.

Vascular Endothelial Growth Factor Receptor-2↗

PubMed2026

Cerebellar iTBS enhances gait adaptation by modulating cortical sensorimotor network dynamics: a randomized controlled trial.

Gait adaptation enables individuals to maintain locomotor stability under persistent perturbations. Although the cerebellum is critical for sensory prediction error-based (SPE) adaptation, how cerebellar neuromodulation reshapes cortical sensorimotor networks to enhance gait adaptation remains unclear. This study investigated the behavioral effects and underlying cortical neurodynamic mechanisms of cerebellar intermittent theta-burst stimulation (iTBS) on gait adaptation. Thirty-two healthy adults received either active or sham cerebellar iTBS. Participants performed a split-belt treadmill adaptation task before and after intervention. Cortical responsiveness was evaluated using TMS-evoked EEG over primary motor cortex (M1), while resting-state EEG was analyzed to assess spectral power and directional functional connectivity. Compared to sham, cerebellar iTBS significantly enhanced gait adaptation, evidenced by a faster adaptation rate (p = 0.035) and enhanced Early Adaptation SLS (p = 0.011), without altering initial perturbation responses or post-adaptation outcomes. The iTBS increased TMS-evoked α (p = 0.031) and γ (p = 0.022) power in M1, while the α power was correlated with faster adaptation (r = 0.526, p = 0.002). Furthermore, iTBS strengthened PPC-to-M1 directed connectivity in the β (p = 0.025) and γ (p = 0.013) bands. Enhanced parieto-motor directionality were positively associated with adaptation rate (β: r = 0.515, p = 0.003; γ: r = 0.463, p = 0.009). These findings suggest that cerebellar iTBS facilitates gait adaptation by modulating cortical responsiveness and directional sensorimotor network connectivity, providing multi-level neurodynamic evidence for the cerebello-cortical modulation during gait adaptation and offering a strong physiological rationale for targeted neuromodulation in gait rehabilitation strategies.

Humans↗

PubMed2026

Effect of urinary catheter securement band on meatal pressure injury in male intensive care patients: A randomized controlled trial.

OBJECTIVES: To investigate the effectiveness of a urinary catheter securement band in preventing meatal pressure injury (meatal-PI) in male ICU patients, and to identify associated risk factors and the timing of injury development. METHODS: A total of 248 adult male ICU patients were randomly allocated to an intervention group (n = 124) or a control group (n = 124) between December 2024 and April 2025. The intervention group received a catheter securement band in addition to standard care, while the control group received standard care alone. Meatal-PI was evaluated daily using a structured monitoring form and a validated staging system. RESULTS: The incidence of meatal-PI was significantly lower in the intervention group (6.5%) compared with the control group (16.1%) (p = 0.016). Multivariate analysis identified catheter securement, use of silicone catheters, higher Braden Scale scores, and shorter ICU length of stay as independent protective factors, while advanced age was associated with increased risk. Additional factors significantly associated with meatal-PI included comorbidities, higher device burden, latex catheter use, dry skin, lower Glasgow Coma Scale and Braden scores, sedation, and perineal oedema (p < 0.001). CONCLUSIONS: The use of a catheter securement band significantly reduces the incidence of meatal-PI in male ICU patients. Incorporating catheter securement devices into routine nursing care, prioritising silicone catheter use, and performing regular meatal assessments may enhance patient safety by reducing the risk of device-related pressure injuries. Further research comparing different catheter securement methods across diverse patient populations is warranted. IMPLICATIONS FOR CLINICAL PRACTICE: The use of catheter securement bands may reduce the incidence of meatal-PI in male ICU patients. Incorporating standardized catheter stabilization strategies into routine intensive care nursing practice may enhance patient safety and support pressure injury prevention efforts.

Humans↗

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

Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5 wt%) and increasing Sr contents (0.5, 1.0, 1.5 wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-α and TGF-β; with an enhanced TNF-α secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

Animals↗

PubMed2026

Determination of 13 per- and polyfluoroalkyl substances in human plasma samples using LC-MS/MS: application to capillary microsamples.

Per- and polyfluoroalkyl substances (PFAS) are chemicals widely applied in industrial processes and highly persistent in the environment, whose extensive use has been linked to adverse health effects. Venous plasma is the conventional matrix for PFAS assessment in blood, and LC-MS/MS is the most used quantification technique. Despite the relevance of this topic, biomonitoring data on human exposure to PFAS in Brazil remain limited. This study validated an LC-MS/MS method for determination of 13 PFAS in human plasma. Blood samples were collected from volunteers by phlebotomy, followed by protein precipitation with acetonitrile containing 1% formic acid (v/v) and solid-phase extraction. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column. The assay was linear over a calibration range of 0.2-20 ng/mL. Intra- and inter-assay precision (CV%) were within the ranges of 2.06-12.0% and 0.25-10.7%, respectively. As for accuracy, results were 89.0-112.9%. Matrix effect ranged from -1.31 to 0.05%. Stability after four freeze/thaw cycles and under autosampler conditions were also confirmed for all analytes. The method was applied to 40 paired venous and capillary plasma samples. Both measures exhibited high correlation (r = 0.926). PFOS was the only compound detected at concentrations ≥0.2 ng/mL (LLOQ) in all samples, with capillary plasma concentrations of 0.85-13.50 ng/mL. In summary, the method showed good validation performance and demonstrated the suitability of capillary plasma samples as an alternative matrix for PFAS quantification.

Humans↗

PubMed2026

Comparison of the predictive performance of systemic immune-inflammation index and neutrophil-to-lymphocyte ratio for three-month poor functional outcome in ischemic stroke: a systematic review and meta-analysis.

INTRODUCTION: Ischemic stroke (IS) is a leading cause of global mortality and disability. Early and accurate prognosis is crucial for patient management. The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) are emerging inflammatory biomarkers; however, their relative predictive value for three-month poor functional outcome (modified Rankin Scale [mRS] > 2) remains uncertain. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library up to 20 July 2025, adhering to PRISMA guidelines. Observational studies reporting the association of SII or NLR with three-month poor outcome were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Area under the curve (AUC), odds ratios (OR), and standardized mean differences (SMD) were pooled using random-effects models in Stata 16.0. RESULTS: Twenty-one studies involving 7520 IS patients were analysed. NLR demonstrated marginally superior discriminative ability compared to SII (AUC 0.71, 95% CI: 0.67-0.76 vs. 0.68, 95% CI: 0.64-0.71), though this difference was not statistically significant. Elevated NLR was significantly associated with poor outcome (OR = 1.26, 95% CI: 1.17-1.37, p < .001), whereas SII was not (OR = 1.00, 95% CI: 1.00-1.00, p = .384). Both markers showed moderate effect sizes (SMD: NLR = 0.69, SII = 0.72; p < .001). NLR performed better in non-intervention and Chinese subgroups, while SII exhibited consistent AUC values across treatment and ethnic subgroups. CONCLUSION: NLR and SII are accessible prognostic markers in IS. NLR demonstrates superior accuracy and a significant association with poor outcome, while SII shows greater stability across patient subgroups. Both may assist in risk stratification, in resource-limited settings.

Humans↗

PubMed2026

Form and function of actin impacts actin health and aging.

The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin structure and function influence lifespan and various hallmarks of aging in Caenorhabditis elegans. Whole-animal and tissue-specific knockdown of actin and key actin-binding proteins (ABPs)-arx-2 (Arp2/3), unc-60 (cofilin), and lev-11 (tropomyosin)-led to premature disruption of filament organization, reduced lifespan, and tissue-specific physiological defects. Actin dysfunction also displayed a more "aged" transcriptome using previously validated transcriptomics clocks, and broadly exacerbated many age-associated phenotypes, including mitochondrial dysfunction, lipid dysregulation, loss of proteostasis, impaired autophagy, and intestinal barrier failure. Pharmacological destabilization with Latrunculin A mirrored genetic knockdowns, while mild stabilization with Jasplakinolide modestly extended lifespan, emphasizing that optimal and finely tuned actin function is critical for healthy aging. Finally, analysis of human genome-wide association data revealed that common ACTB polymorphisms correlate with differences in age-related decline in gait speed, suggesting some links between aging and actin across organisms. Taken together, our results provide a comprehensive and publicly accessible resource that maps, for the first time, how changes in actin integrity correlate with diverse aging phenotypes across tissues. This descriptive framework is intended to enable future mechanistic discovery by offering a deep, unbiased dataset that can be integrated with emerging studies to define how actin dynamics can potentially influence aging.

actin↗

PubMed2026

Effect of ketofol versus Fentanyl-Midazolam sedation on neurological recovery in traumatic brain Injury: A randomised study.

Neurological recovery after traumatic brain injury (TBI) is multifactorial, and sedation is a cornerstone of neurocritical care because of its neuroprotective role. Although ketofol is widely used for anaesthesia, its effectiveness as a sedative regimen in the intensive care unit (ICU) has not been well studied. This preliminary exploratory double-blind, randomised study compared ketofol (KP) with fentanyl-midazolam (FM) sedation in adults with moderate-to-severe TBI. Sedation was administered for 72 h and titrated to a Richmond Agitation-Sedation Scale (RASS) score ≤  - 3. The primary outcome was the Extended Glasgow Outcome Scale (GOSE) at 30 days. Secondary outcomes included GOSE at 90 days, incidence of propofol infusion syndrome (PRIS), duration of mechanical ventilation, haemodynamic stability, and ICU and hospital length of stay. Of 120 enrolled patients, 111 were included in the final analysis (57 FM, 54 KP). Baseline characteristics, including injury severity and Marshall CT scores, were comparable. At 30 days, good neurological recovery (GOSE 7-8) was more frequent in the KP group than the FM group (26% vs. 10.5%, p = 0.03). At 90 days, recovery remained higher with KP (44.4% vs. 33.3%), though the difference was not statistically significant (p = 0.16). Multivariate analysis confirmed ketofol as an independent predictor of good recovery at 30 days (adjusted OR 3.63, 95% CI 1.11-11.85, p = 0.033). No PRIS occurred, and secondary outcomes were similar. Ketofol-based sedation was safe and may be associated with improved early neurological recovery compared with fentanyl-midazolam, with a favourable trend toward improved long-term neurological recovery.

Humans↗

PubMed2026

Effects of CPAP on endothelial activation and fibrinolytic balance in coronary artery disease with obstructive sleep apnea: The RICCADSA randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) promotes endothelial activation and a prothrombotic milieu through intermittent hypoxia, oxidative stress, and systemic inflammation, mechanisms closely linked to atherosclerosis progression. The vascular effects of continuous positive airway pressure (CPAP) therapy in patients with established coronary artery disease (CAD) remain incompletely understood. OBJECTIVE: To evaluate the longitudinal effects of CPAP treatment on endothelial adhesion molecules and fibrinolytic balance in patients with CAD and OSA. METHODS: In this randomized controlled analysis from the RICCADSA trial, 210 revascularized CAD patients with moderate-to-severe OSA were assigned to CPAP (n = 104) or no-CPAP (n = 106) and had available biomarker measurements at baseline and 12 months. Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1) were assessed. Linear mixed-effects models were used to examine longitudinal changes and time-by-treatment interactions adjusted for cardiometabolic covariates. RESULTS: For ICAM-1, no significant time-by-treatment interaction was observed. For PAI-1, a borderline time-by-treatment interaction suggested a numerically smaller increase in the CPAP group compared with no-CPAP (p = 0.09). CPAP treatment was associated with a significantly greater reduction in VCAM-1 over time compared with no-CPAP (time-by-treatment interaction p = 0.045 in adjusted models). CONCLUSIONS: CPAP treatment was associated with selective modulation of vascular biomarkers in patients with CAD and OSA, characterized by attenuation of endothelial activation reflected by reduced VCAM-1 levels, while fibrinolytic imbalance appeared largely resistant to intervention. These findings support pathway-specific vascular responses to CPAP and provide mechanistic insight into residual atherosclerotic risk in this high-risk population.

Aged↗

PubMed2026

Association of galectin-3 in systemic lupus erythematosus: A systematic review and meta-analysis.

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune condition showing persistent profiling of inflammation and damage of organs and immune system. Amongst many biomarkers for such autoimmune diseases, Galectin-3 (Gal-3) a β-galactoside-binding lectin responsible for regulation, inflammation, and fibrosis of immune repsonses, has engrossed researchers for further investigations as a potential biomarker. However, correlation has been studied between circulating Galectin-3 levels and SLE but outcomes still remain inconsistent. Therefore, this systematic review and meta-analysis evaluated the association between circulating galectin-3 levels and SLE.Materials and MethodsPubMed, Scopus, ScienceDirect, Web of Science, and Embase databases are extensively used for literature search. The last database search was conducted on September 6, 2025. Eligible studies included case control studies reporting circulating galectin-3 levels in individuals with SLE and healthy controls. Two independent reviewers performed study selection and data extraction. Study quality was evaluated using the Newcastle-Ottawa Scale. Comprehensive Meta-Analysis software was used for statistical analysis. Pooled effect sizes were calculated as mean differences with 95% confidence intervals. Heterogeneity was assessed using the Cochrane Q test and I2 statistics, and publication bias was evaluated using Begg's funnel plot and Egger's regression analysis.ResultsSeven eligible studies were included in the meta-analysis. The pooled results showed that patients with SLE had significantly higher circulating Galectin-3 levels than healthy controls (mean difference = 8.48; 95% CI: 3.84-13.12; p < 0.0001). Substantial heterogeneity was observed across studies (Tau square: 32.57, Q = 196.03; p < 0.0001, I2 = 96.93%). Sensitivity analysis confirmed the stability of the overall findings. Begg's funnel plot and Egger's regression analysis indicated no publication bias among studies. Subgroup analysis supports the results of the overall analysis.ConclusionThis meta-analysis depicts that galectin-3 may serve as a biomarker associated with SLE pathogenesis and inflammatory activity due to significantly elevated levels of circulating galectin-3 levels in patients with systemic lupus erythematosus.

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

Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study.

OBJECTIVE: Muscle weakness is prevalent in rheumatoid arthritis (RA), osteoarthritis (OA) and sarcopenia (SARC). Endurance exercises may improve mitochondrial function and oxidative capacity, while strength exercises are thought to stimulate myofibrillar protein synthesis. This study aims to compare the effects of strength and endurance exercise and explore the association between muscle characteristics and exercise outcomes in patients with RA, OA and SARC. We hypothesize that responses to endurance and strength exercises in patients with muscle weakness are influenced by intramuscular pathology including muscle morphology, mitochondrial function, and systemic inflammation, based on their disease pathology, potentially requiring personalized training schedules. METHODS: This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n = 35) or muscle strength exercises (n = 34), using minimization to balance disease type and gender. The 8-week intervention includes two supervised sessions per week using a controlled cable pulley device (Reforter™) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system®. Secondary outcomes include muscle morphology, mitochondrial function, systemic inflammation and muscle endurance (by Biodex and 6 Minute Walk test). Muscle morphology will be assessed via 3D ultrasound imaging of the vastus lateralis. Mitochondrial function will be analyzed using high-resolution respirometry on muscle biopsies. Systemic inflammation will be measured using multiplex assays or ELISA on serum samples. DISCUSSION: This study will explore differential responses to muscle endurance and muscle strength exercises in patients with RA, OA, and SARC, offering novel insights into the molecular mechanisms of muscle weakness. The findings may help identify potential mechanisms underlying variability in exercise response and provide effect size estimates to guide future confirmatory studies and more targeted exercise interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06480643 (date of registration28-06-24).

Humans↗

PubMed2026

Omics in hereditary optic neuropathies: A systematic review of clinical studies with an integrated point of view.

Hereditary optic neuropathies are characterized by bilateral visual loss due to the degeneration of retinal ganglion cells, resulting in optic nerve degeneration and atrophy. Although the genetic origin of the main isolated and syndromic hereditary optic neuropathies has been characterized, the clinical phenotypes exhibit significant and poorly understood variability in both penetrance and expressivity. Additionally, the genetic and environmental factors that influence the onset of these optic neuropathies remain poorly understood, with limited biomarkers to predict disease progression or as readouts for therapeutic trials. Data-driven omics strategies allow deep phenotyping to improve our understanding of pathophysiological mechanisms and to search for new biomarkers and therapeutic targets. We explore whether the omics strategies applied to patients with hereditary optic neuropathies have provided such new insights. MEDLINE, Web of Science and EMBASE databases were screened for studies with terms relating to hereditary optic neuropathies, transcriptomics, epigenomics, proteomics, metabolomics and lipidomics in clinical studies exploring patients' samples. Out of 1244 references identified, 22 articles were included after double-masked data curation. These articles focused only on the 3 main forms of hereditary optic neuropathies, namely, OPA1-related dominant optic atrophy (n = 4), Leber hereditary optic neuropathy (n = 13), and Wolfram syndrome (n = 5). While the methodological designs and results of these studies were highly heterogeneous, they revealed molecular alterations that we have attempted to discuss at the integrated multi-omics level. This data integration highlighted several common pathophysiological mechanisms such as energetic impairment, endoplasmic reticulum stress, proteotoxic and oxidative stresses, lipid remodeling and altered amino acid and purine metabolisms, while suggesting potential new biomarkers and therapeutic targets. These findings underscore the potential of integrated multi-omics approaches to deepen our understanding of the phenotypic complexity of hereditary optic neuropathies and to support the development of innovative diagnostic and therapeutic strategies.

Humans↗