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PubMed2026

Epigenetic Clocks of Biological Aging and Cognitively Healthy Longevity: The Women's Health Initiative Memory Study.

BACKGROUND: Little is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODS: We examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n = 1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n = 956, 16.4%); vs. 3) death before age 90 (n = 2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. RESULTS: Each standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR = 0.66; 95% CI 0.61-0.71), PCGrimAge (OR = 0.64; 95% CI 0.59-0.69), PCPhenoAge (OR = 0.73; 95% CI 0.68-0.78) and DunedinPACE (OR = 0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. CONCLUSION: All epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.

Healthspan↗

PubMed2026

ADAM10's combined influence on the diagnostic usefulness of IL 22, IL 10, IL-17 A, and IL-17D in autism spectrum disorders: Predicted role on gut leakiness as co-morbidity.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with increasing global prevalence but a lack of reliable diagnostic biomarkers. Emerging evidence suggests that immune dysregulation, gut-brain axis dysfunction, and increased intestinal permeability play key roles in ASD pathophysiology. This study investigated the combined diagnostic value of ADAM10 and cytokines (IL-10, IL-22, IL-17 A, and IL-17D). Multivariable logistic regression produces an improved ROC curve that improves diagnostic accuracy over individual markers by combining numerous predictors into a single risk score (linear predictor). The technique, which frequently raises individual marker AUCs, entails modelling a binary result, calculating the probability, and visualizing ROC based on the projected probabilities. In this case-control study, plasma levels of ADAM10, IL-10, IL-22, IL-17 A, and IL-17D were measured in 37 male children with ASD and 37 age-matched controls. Group comparisons, correlation analyses, and receiver operating characteristic (ROC) curve analyses, including combined ROC models, were performed. ADAM10, IL-22, and IL-17 A levels were significantly reduced in children with ASD compared to controls, whereas IL-10 and IL-17D showed no significant differences. ADAM10, IL-17 A, and IL-22 demonstrated good diagnostic performance, with AUC values of 0.886, 0.855, and 0.812, respectively. In contrast, IL-10 and IL-17D showed poor discriminatory ability, with AUC values of 0.524 and 0.599, respectively. Combined ROC analysis markedly improved diagnostic accuracy, with all panels including ADAM10 achieving AUC values above 0.90, and some reaching as high as 0.988, with high sensitivity and specificity. The combination of ADAM10 with selected cytokines significantly enhances diagnostic performance compared to individual markers, supporting a link between immune dysregulation, barrier dysfunction, and gut permeability in ASD.

Humans↗

PubMed2026

Theta-range SEEG stimulation for intracranial mapping: extending conventional 1-Hz and 50-Hz protocols.

OBJECTIVE: Electrical brain stimulations (EBS) are central to epileptic network identification and functional mapping during stereo-electroencephalography, yet stimulation frequencies remain empirical, and standardized across patients and brain regions, producing false negatives and false positives, and potentially compromising surgical outcome. We prospectively investigated theta-range EBS (7 Hz) in the temporal lobe, a prominent physiological frequency band in this region, and compared it with conventional 1-Hz and 50-Hz protocols. METHODS: We analyzed 1,408 temporal EBS in 25 drug-resistant epileptic patients. Epileptic responses (afterdischarges, seizures) and clinical signs were assessed across the epileptic network and temporal structures (amygdala, hippocampus, neocortex, parahippocampal gyrus, white matter), and confronted to stimulation parameters (frequency, intensity, duration, total charge). RESULTS: At matched intensity and duration, 7-Hz EBS were associated with a higher occurrence of afterdischarges and clinical signs than 1-Hz EBS in several temporal structures. Effects on usual seizure induction were less consistent. Comparisons with 50 Hz showed no systematic significant differences, with responses observed at one or both frequencies depending on structure and outcome. When controlling for total charge, frequency-related differences were attenuated. Some effects were sporadically observed at both intermediate frequency and charge quantity. CONCLUSIONS: EBS responses emerge from the interaction between all electrical parameters and anatomical location and local excitability, and can hardly be disentangled. However, 7-Hz EBS can provide complementary clinical information during temporal-lobe mapping, with a targeted approach. SIGNIFICANCE: These findings support targeted evaluation of broader stimulation parameter spaces, including intermediate frequencies, rather than routine reliance on fixed low- and high-frequency protocols alone.

Humans↗

PubMed2026

Effects of Sacubitril Valsartan Combined With Vericiguat on NT-proBNP and CK-MB Levels in Patients With Chronic Heart Failure.

This study aims to probe the influence of sacubitril valsartan sodium tablets combined with vericiguat on N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatine kinase isoenzyme (CK-MB) levels in patients with chronic heart failure (CHF). One hundred and twenty CHF patients were enrolled and stratified into a control group (sacubitril valsartan sodium tablets) and a combination group (sacubitril valsartan sodium tablets + vericiguat). Outcome measures included New York Heart Association (NYHA) functional class shifts, echocardiographic indices, cardiac injury markers, 6-min walk distance (6MWD), endothelial function parameters, inflammatory mediator levels, and adverse clinical events. Following a 6-month treatment period, patients in the combination group exhibited superior functional improvement, as reflected by greater advancement in NYHA class. Echocardiographic evaluation revealed more favorable ventricular remodeling in this group, with reduced left ventricular end-diastolic and end-systolic diameters and an elevated ejection fraction. The combination group had a higher 6MWD. Biomarker analysis showed lower NT-proBNP and CK-MB levels in the combination group. Furthermore, improvements in endothelial function were noted, with decreased endothelin and elevated NO, NOS, and CGRP levels in the combination group. Markers of systemic inflammation, including CRP and IL-6, were also attenuated in the combination group. The incidence of adverse reactions and cardiovascular events did not differ significantly between the groups. Co-administration of sacubitril/valsartan and vericiguat enhances cardiac performance, optimizes vascular endothelial responsiveness, modulates heart failure-related biomarkers, and mitigates inflammatory activity in patients with CHF without increasing the risk of adverse events.

Humans↗

PubMed2026

Cross-tissue multi-omics integration highlights BPHL and mitochondrial targets in Alzheimer's disease.

BACKGROUND: Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), yet specific molecular targets remain to be fully characterized. METHODS: A summary-data-based Mendelian randomization (SMR) framework integrated AD genome-wide association study (GWAS) statistics (39,918 cases) with blood DNA methylation quantitative trait loci (mQTL), gene expression (eQTL), and protein (pQTL) data for 1136 mitochondria-related genes. Associations were assessed using Bayesian colocalization and HEIDI testing. Tissue relevance was evaluated in four brain regions (hippocampus, amygdala, cortex, frontal cortex) using GTEx and external transcriptomic datasets. RESULTS: Screening identified eight candidates supported across blood mQTL and eQTL layers. Stepwise central nervous system (CNS) evaluation singled out biphenyl hydrolase-like (BPHL) as the consistent candidate. Higher genetically predicted BPHL expression was associated with reduced AD risk across the hippocampus (OR=0.920, 95% CI 0.873-0.970), amygdala (OR=0.925, 95%CI 0.880-0.973), cortex (OR=0.943, 95% CI 0.908-0.978), and frontal cortex (OR=0.938, 95%CI 0.901-0.976). These findings aligned with protein-protein interactions connecting BPHL to respiratory complexes and lower BPHL expression in independent AD brains. Functional enrichment converged on oxidative phosphorylation pathways. CONCLUSIONS: By integrating multi-omics data with tissue-specific validation, this study nominates BPHL as a consistent protective candidate in the brain. These findings provide genetic support for mitochondrial molecular perturbations in AD, offering insights for future validation.

Alzheimer Disease↗

PubMed2026

Lipid metabolism is a key central, systemic and gut microbial feature of the decline in rat hippocampal function during middle age.

Middle age is emerging as a turning point in brain ageing, prognostic of future cognitive health and amenable to intervention. Metabolic and proteomic differences during this period are not yet fully understood and may potentially influence functions of the hippocampus, a brain area that regulates memory and anxiety. While the gut microbiota is implicated in brain ageing, the relationship between the gut microbiota, the metabolic state, and hippocampal proteome in middle age has not been investigated. We hypothesise that peripheral metabolic or protein features are associated with hippocampal vulnerability in middle age. Therefore, young adult and middle-aged rats were assessed for behavioural, proteomic, metabolic, and gut microbiota differences. Proteomic profiling of the hippocampus revealed differential expression of proteins indicative of altered synaptic signalling. Concurrently, adult hippocampal neurogenesis was decreased in middle age. Hippocampal microglia exhibited a lipid rich, inflammatory phenotype in middle age which correlated with poorer memory performance. CSF and serum proteomic and metabolomic analyses identified dysregulated lipid-related pathways potentially contributing to hippocampal vulnerability in middle age. Furthermore, 16S rRNA sequencing revealed reduced abundance of bacteria involved in lipid metabolism regulation. However, faecal microbiota transfer from young to middle aged rats was not sufficient to robustly improve hippocampus-dependent spatial memory. Together, these findings highlight dysfunctional lipid metabolism as a key feature of middle age that may contribute to decline in hippocampal function. Given that the scope for intervention is limited during older age, targeting biomarkers involved in metabolic and lipid homeostasis may be pivotal for the development of pharmacological or lifestyle-based interventions during middle age which could ultimately delay future cognitive ageing.

Animals↗

PubMed2026

Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of auditory nerve output after threshold recovery.

BACKGROUND: Acoustic stress can alter cochlear function even in the absence of permanent threshold elevation; however, synaptic consequences of transient acoustic stimulation remain incompletely understood. OBJECTIVE: This study aimed to investigate whether transient acoustic stimulation induces changes in the auditory nerve output and cochlear ribbon synapse morphology following hearing threshold recovery. METHODS: Young adult CBA/CaJ mice were exposed to band-limited acoustic stimulation (45-2,000 Hz, 95 dB SPL, 2 h). Auditory brainstem responses (ABRs), hair cell and spiral ganglion neuron survival, and synaptic morphology were evaluated before exposure and up to 2 weeks post-exposure. RESULTS: ABR thresholds were transiently elevated immediately after exposure but largely recovered by 1 day post-exposure. In contrast, ABR wave I amplitudes significantly increased after threshold recovery across multiple test frequencies. Ribbon-associated puncta in both inner and outer hair cell regions exhibited biphasic temporal changes, with an initial decrease immediately after exposure followed by an increase at 1 day post-exposure. The ribbon-associated punctal area also increased after exposure and remained elevated at later post-exposure time points. No significant loss of hair cells or spiral ganglion neurons was observed. Exploratory genomic analysis suggested enrichment of pathways related to metabolic defense and cellular stress responses. CONCLUSIONS: Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of peripheral auditory nerve output without overt cellular degeneration. These findings support a model in which early cochlear responses to acoustic perturbation include adaptive synaptic plasticity and gain regulation, extending current concepts of noise-induced cochlear change beyond irreversible synaptic loss.

Animals↗

PubMed2026

Thrombus Metabolism-Based Molecular Subtyping for Prognostic Risk Stratification in Acute Ischemic Stroke: A Preliminary Study.

AIMS: To preliminarily characterize metabolic molecular subtypes of cerebral thromboemboli and evaluate their clinical significance in anterior circulation acute ischemic stroke due to large vessel occlusion (AIS-LVO). METHODS: Untargeted metabolomics was performed on thromboemboli retrieved from 36 patients with anterior circulation AIS-LVO using ultra-performance coupled liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Unsupervised hierarchical clustering was employed to identify distinct metabolic molecular subtypes, and their associations with stroke etiology, radiographic severity, and functional outcomes were analyzed. RESULTS: Two distinct thrombus metabolic molecular subtypes (C1 and C2) were identified based on 12 metabolites significantly associated with both short-term (7-day ∆NIHSS) and long-term (90-day mRS) functional outcomes. The C1 subtype, predominantly cardioembolic, exhibited enhanced lipid metabolism, whereas the C2 subtype, primarily atherothrombotic, demonstrated increased folate metabolism. Patients with C1 thromboemboli presented more severe admission ischemic lesions (as indicated by ASPECTS) and experienced poorer short-term and long-term outcomes. A six-metabolite signature derived from LASSO regression was identified for exploratory discrimination of thrombus metabolic subtypes, etiological subtypes, and 90-day outcomes. CONCLUSION: This preliminary exploratory study identifies two metabolically distinct thrombus molecular subtypes with clinical implications in anterior circulation AIS-LVO, providing a novel basis for risk stratification and personalized secondary prevention and warrants further investigation.

Humans↗

PubMed2026

Gout and allopurinol adherence in newly diagnosed patients and the risk of fractures: a nationwide cohort study.

INTRODUCTION / OBJECTIVES: The association between gout and fractures remains controversial due to the competing effects of uric acid's antioxidant properties and gout-induced chronic inflammation. Our study aimed to evaluate the risk of fractures in newly diagnosed gout patients and to analyze the impact of Allopurinol medication adherence on this risk. METHODS: This nationwide cohort study utilized the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database (2002-2019). We identified 4,107 patients newly diagnosed with gout who remained on continuous allopurinol therapy during the 24-month medication assessment period and matched them 1:3 with 12,321 non-gout controls using propensity score matching. Allopurinol adherence was assessed via the Medication Possession Ratio (MPR) over a 24-month period and categorized into three groups: MPR < 0.3, 0.3 ≤ MPR < 0.8, and MPR ≥ 0.8. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for fractures (vertebral, hip, and distal radius). RESULTS: Gout patients demonstrated a significantly higher risk of overall fractures compared to the non-gout group (aHR 5.52; 95% CI 4.19-7.26). A significant inverse linear relationship was observed between allopurinol adherence and fracture risk (P for trend < .001). The risk was highest in the low-adherence group (MPR < 0.3; aHR 5.91; 95% CI 4.40-7.93) and relatively lower in the high-adherence group (MPR ≥ 0.8; aHR 4.77; 95% CI 2.94-7.72). Consistent trends were observed for vertebral (aHR 5.68) and hip (aHR 4.22) fractures. These associations remained consistent across all subgroups, including age, sex, and comorbidities. CONCLUSION: Newly diagnosed gout is associated with a substantially increased risk of fractures. Higher adherence to Allopurinol therapy is correlated with a significant reduction in this risk, suggesting that consistent urate-lowering therapy may mitigate gout-related bone fragility. Key Points • Newly diagnosed gout patients have a significantly higher risk of major osteoporotic fractures compared to the non-gout population. • A significant inverse linear relationship exists between Allopurinol adherence and fracture risk, with the highest adherence group (MPR ≥ 0.8) showing a relatively lower risk. • Consistent urate-lowering therapy (ULT) may mitigate bone fragility in gout patients by reducing systemic inflammatory burden caused by urate crystal deposition.

Humans↗

PubMed2026

Sex-dependent protective effects of microglial tumor necrosis factor on post-stroke inflammation and myelin injury.

Tumor necrosis factor (TNF) is rapidly induced after ischemic stroke, but its proposed cell-specific and sex-dependent functions during post-stroke inflammation remain insufficiently understood. Here, we investigated the role of microglia-derived TNF in the acute and subacute response to permanent middle cerebral artery occlusion (pMCAO). Tnf expression was transiently upregulated after stroke, becoming significant at 4 h, peaking at 12-24 h, and returning to baseline by 5 days. In situ hybridization confirmed strong Tnf expression in the infarct and peri-infarct regions. Whole-brain transcriptomic profiling showed that global TNF deficiency reshaped the early post-ischemic response, shifting it from microglia-associated phagocytic and wound-healing pathways toward an interferon-related inflammatory signature. To define the specific contribution of microglial TNF, we used inducible Cx3cr1CreER:Tnffl/fl mice. Microglial TNF deletion had no effect on infarct volume in males at 24 h or 5 days after pMCAO, but significantly increased infarct size in females at both time points. In both sexes, brain TNF levels peaked at 24 h and were significantly reduced in Cx3cr1CreER:Tnffl/fl mice, confirming microglia as a major source of early post-ischemic TNF. However, downstream consequences diverged by sex. At 5 days, male Cx3cr1CreER:Tnffl/fl mice showed reduced microglial reactivity and 18 kDa translocator protein (TSPO) signal, with no change in T-cell infiltration, and exhibited increased density of mature oligodendrocytes. In contrast, female Cx3cr1CreER:Tnffl/fl mice displayed enhanced microglial reactivity, increased TSPO binding, higher peri-infarct T-cell infiltration, and reduced oligodendrocyte density and myelin integrity. Together, these findings identify microglial TNF as a sex-dependent regulator of post-stroke inflammation and myelin injury.

Animals↗

PubMed2026

Microglial modulation in general anesthesia: molecular.

General anesthetics profoundly alter brain function and consciousness, yet the mechanisms underlying these effects remain incompletely understood. Although traditional studies have primarily focused on neuronal targets, accumulating evidence suggests that microglia dynamically respond to anesthetic exposure and may participate in anesthesia-associated neurophysiological changes. Beyond their established immune functions, microglia are increasingly implicated in synaptic remodeling, metabolic regulation, neuronal activity surveillance, and neuron-glia communication. Recent studies indicate that different classes of anesthetic agents modulate microglial activity through diverse and context-dependent mechanisms involving inflammatory signaling, purinergic pathways, calcium dynamics, mitochondrial metabolism, and neural circuit interactions. These responses are associated with postoperative neurocognitive disorders, altered synaptic plasticity, and anesthesia-related changes in brain states. In this review, we summarize current evidence regarding the effects of volatile anesthetics, intravenous anesthetics, and analgesics on microglial function and discuss the molecular, functional, and circuit-level mechanisms underlying anesthesia-associated neuron-microglia interactions. We further highlight the dynamic and heterogeneous nature of microglial responses during anesthesia and discuss current limitations in the field, including the lack of temporally resolved and cell-specific approaches. Understanding these processes may provide insights into anesthesia-associated neurocognitive dysfunction and support the development of neuroimmune-targeted strategies in anesthesiology.

General anesthesia↗

PubMed2026

Accurate quantification of canine mitochondrial DNA copy number from canine blood and brain samples.

Acute brain injury is difficult to evaluate in veterinary medicine and tools to investigate the potential involvement of mitochondrial involvement are limited. The brain is highly enriched in mitochondria and contains thousands of copies of mitochondrial DNA (mtDNA) per cell, but robust methods for quantifying mitochondrial DNA copy number (mtDNA-CN) in canine tissues are lacking. We describe the development of a quantitative real-time PCR assay for absolute measurement of mtDNA-CN which was validated in canine blood and brain tissue. To minimize amplification of nuclear mitochondrial insertion sequences (NumtS) and repetitive regions, species-specific oligonucleotide primers were designed following in silico genomic filtering. The assay was applied to a small pilot cohort comprising blood samples from dogs with and without acute brain injury (n = 4-6 per group) and cerebral cortex samples (n = 1 per group) to assess feasibility and biological plausibility. In non-brain injury dogs, blood mtDNA-CN ranged from 98 to 288 copies per nuclear genome (mean 193 ± 72), while values in brain-injured cases ranged from 163 to 228 copies per genome (mean 200 ± 33). Cerebral cortex samples exhibited higher mtDNA-CN than blood, consistent with known tissue-specific mitochondrial enrichment. In a single brain-injured case with serial sampling, mtDNA-CN increased over five days. This study presents a validated assay and pilot data for mtDNA-CN quantification in canine samples. While not powered for biomarker evaluation, this method may enable future studies of mitochondrial dynamics in canine brain injury and metabolic disease.

Animals↗

PubMed2026

The role of artificial intelligence in the diagnosis and prognosis of traumatic brain injury based on brain CT scans: a systematic review.

Traumatic brain injury (TBI) is a leading cause of emergency department visits and a major contributor to injury-related mortality and long-term neurological disability. Non-contrast computed tomography (CT) is the gold-standard imaging modality for the rapid diagnosis of TBI. Clinical outcomes depend strongly on early detection and prompt acute management. Artificial intelligence (AI)-based models may support faster automated identification of traumatic findings and early prediction of patient prognosis. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, IEEE Xplore, ACM Digital Library, and the Cochrane Library in accordance with PRISMA 2020 guidelines to evaluate AI-based models for automated detection of TBI-related findings on CT and for prediction of clinical outcomes. Risk of bias and applicability were assessed using QUADAS-2 for diagnostic accuracy studies and PROBAST + AI for prediction model studies. Twenty-two studies were included. Sixteen studies evaluated diagnostic tasks and 10 evaluated prognostic outcomes, with four studies contributing to both categories. Diagnostic performance was generally high, with many studies reporting AUC values approaching or exceeding 0.90, particularly for larger lesion volumes.Prognostic performance was more variable, with moderate to high discrimination and substantial heterogeneity. Only 9 studies incorporated independent external validation, and performance was frequently lower in external cohorts. All prognostic model studies were judged to be at high overall risk of bias using PROBAST + AI, and most diagnostic accuracy studies also demonstrated high or unclear risk of bias in at least one QUADAS-2 domain, most frequently in patient selection. AI-based models applied to brain CT demonstrate strong technical performance for both diagnostic and prognostic tasks in TBI. However, most studies relied on retrospective designs and lacked independent external validation which limits models generalizability and raises concern for potential overfitting. Prospective, multicenter studies with standardized methodologies and rigorous external validation are required before widespread clinical implementation.

Humans↗

PubMed2026

Somatic mutations: recent advances in brain aging and neurodegeneration.

Somatic mutations are genetic variants that occur after the single-cell phase of development and have been implicated in disease pathogenesis. While most DNA lesions are detected and repaired, examination of healthy tissue has revealed that some lesions escape repair, leading to somatic mutations that accumulate at a consistent rate, including in human brain tissue and postmitotic neurons. Emerging methodological and analytical advances have revealed the presence of persistent mutagenic mechanisms during healthy brain aging as well as mutational pattern shifts in the context of neurodegenerative diseases. Here, we highlight recent methodological advances, summarize our current understanding of somatic mutagenesis in neurotypical brain aging, and examine the role of somatic mutations in neurodegenerative diseases.

Humans↗

PubMed2026

Studies on functional differentiation of xpr1a and xpr1b genes in zebrafish.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is known to be involved in various biological processes, including phosphate homeostasis, cellular signaling, brain and vascular mineralization, whereas its specific contribution to bone development remains incompletely characterized. Due to genome duplication in teleosts, zebrafish Danio rerio possess two paralogous genes of XPR1 namely xpr1a and xpr1b, whose functional divergence remains unclear. The amino acid sequence similarity between zebrafish xpr1a and xpr1b was 83.26%. In situ hybridization demonstrated overlapping localization in the head and spinal cord at 24-48 hpf, while diverged by 72 hpf, with xpr1a becoming restricted to the head while xpr1b persisted in both regions. CRISPR/Cas9 was used to generate xpr1a and xpr1b mutants. The xpr1a mutants are comparatively healthy, viable but with mild growth reduction, whereas the xpr1b mutants display high mortality, reduced body length and severe vertebral deformities. Interestingly, all the double mutants died at the embryonic stage. Moreover, to further investigate the molecular and regulatory mechanisms, we conducted comparative transcriptome analysis on bone and brain tissues from xpr1b+/+ and xpr1b-/- zebrafish. In bone tissue, 6749 DEGs were identified, comprising 3846 upregulated and 2903 downregulated genes. These DEGs were mainly enriched in the MAPK signaling pathway, Wnt signaling pathway, cysteine and methionine metabolism, and ECM-receptor interaction. RT-qPCR validated results showed that seven osteogenesis-related genes (col1a1a, sp7, runx2b, col1a2, col1a1b, alp1 and entpd5), and two phosphate homeostasis related genes (slc20a2 and pdgfba), which are essential for skeletal mineralization and phosphate homeostasis, exhibited significantly downregulated expression in bone tissue of xpr1b mutant zebrafish. These results highlight the pivotal role of xpr1b in regulating skeletal mineralization and phosphate metabolism, thereby elucidating the functional specialization of XPR1 paralogs while providing a theoretical basis for understanding bone developmental mechanism in teleost vertebrates.

Animals↗

PubMed2026

Analysis of the Relationship between Early Clinical Factors and Glasgow Outcome Scale in Patients With Traumatic Brain Injury.

OBJECTIVE: This study aimed to evaluate the association between early clinical factors and the Glasgow outcome scale (GOS) in patients with traumatic brain injury (TBI). METHODS: We conducted a retrospective analysis of 98 TBI patients who underwent emergency surgery between January 2021 and January 2024. Based on GOS scores at 6 months post-surgery, patients were classified into a favorable outcome group (GOS ≥ 4, defined as moderate disability or good recovery, n = 58) and an unfavorable outcome group (GOS < 4, i.e., death, persistent vegetative state, or severe disability, n = 40). Baseline and early clinical parameters were compared between groups. Statistically significant variables from univariate analysis were entered into a multivariate logistic regression model to identify independent prognostic factors. RESULTS: Significant intergroup differences were observed in age, time from injury to surgery, bleeding site, midline shift, Glasgow coma scale (GCS) score at admission, blood glucose level, and D-dimer level (all p < 0.05). Multivariate analysis confirmed that age, time from injury to surgery, GCS score, blood glucose, and D-dimer level were independent predictors of GOS (all p < 0.05). CONCLUSION: Early clinical factors, including age, time to surgery, GCS score, blood glucose, and D-dimer level, independently influence GOS in TBI patients. Time from injury to surgery emerged as a potentially modifiable factor in this cohort, suggesting that minimizing delays may improve outcomes.

Humans↗

PubMed2026

Nimodipine in animal models of demyelination relevant to multiple sclerosis: a systematic review.

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease in which axonal injury, neuronal death, and demyelination occur. Treatment for MS relapses remains limited, which alleviates acute loss of function but has no impact on long-term disability. This study aimed to perform a systematic review of the effects of nimodipine on experimental demyelination models, including experimental autoimmune encephalomyelitis (EAE) and Cuprizone models in rodents. METHODS: This study was conducted following the PRISMA statement. A systematic search was performed in PubMed, Scopus, the Cochrane Library, and Google Scholar. The primary outcome was EAE clinical disease severity (peak clinical score and/or cumulative disease burden). Secondary outcomes included relapse activity (when reported), histological myelin outcomes, oligodendrocyte lineage markers, neuroaxonal injury markers, and inflammatory readouts. Risk of bias was assessed using the SYRCLE tool. RESULTS: Out of 4660 results, 5 studies were included in the systematic review (four EAE studies and one cuprizone model). Nimodipine was administered using heterogeneous regimens (oral, intravenous, intraperitoneal, subcutaneous, or osmotic pump delivery; 1-30 mg/kg/day). The included studies reported the variable effects of nimodipine on relapse-related outcomes, myelination, inflammatory processes, and neuroprotection in the EAE model of MS. Across EAE studies, nimodipine generally reduced clinical disease severity or cumulative burden, although relapse-related outcomes were inconsistent. CONCLUSIONS: Preclinical evidence suggests that nimodipine may attenuate disease severity and demyelination and may promote repair-related processes in rodent models relevant to MS. However, to evaluate the clinical applicability of nimodipine in MS patients, well-powered, transparently reported preclinical replication and early-phase clinical studies are required before clinical translation.

Animals↗

PubMed2026

Epigenetic drift and LINE-1 activation in aging brain: Implications for neurodegenerative disease.

Brain aging and age-associated neurological diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS), are largely attributed to epigenetic drift which is characterized by the gradual accumulation of alterations in neural cell methylation patterns over time. These methylation changes are particularly evident in transposable element (TE)-derived sequences such as Long interspersed element-1 (LINE-1) which comprises approximately 17% of the human genome. During aging, LINE-1 elements gradually lose their methylation, as well as the regulatory safeguard mechanisms that usually keep them inactive. This repression loss can lead to LINE-1 reactivation, contributing to harmful effects including genomic instability, neuroinflammation, and more. Together these findings indicate that impaired epigenetic maintenance, especially in repetitive genome regions, plays a key role in biological aging of neurons and glial cells. In this narrative review, we discuss the methylation dynamics and regulatory mechanisms of LINE-1 retrotransposons, their activation processes during aging, and contribution to age-associated neurological diseases. We also highlight the potential of targeting LINE-1 methylation to restore methylation homeostasis, epigenetic stability and delay brain aging.

Humans↗