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Prenatal exposure to opioids such as morphine poses significant risks to fetal neurodevelopment, particularly in brain regions critical for cognition, such as the hippocampus. Despite the prescription and use of opioids during pregnancy, the molecular and histological consequences of such exposure remain insufficiently explored. To evaluate the effects of short-term prenatal morphine exposure on the expression of key neurodevelopmental genes and the structural integrity of the hippocampus in neonatal rats. Pregnant Sprague Dawley rats were administered intraperitoneal injections of morphine sulfate (10 mg/kg) on gestational days 15 and 16. On postnatal day 12, offspring (n = 6 per group) were euthanized, and their hippocampal tissues were collected. Quantitative real-time PCR was performed to assess the expression levels of neurodevelopmental genes, including MDH2, Neurog1, and BDNF. Histological evaluations were conducted using hematoxylin and eosin and cresyl violet staining to assess cellular architecture and neuronal viability. Immunohistochemical staining for GFAP, S100, and synaptophysin was used to evaluate astrocytic integrity and synaptic density. The morphine-exposed group showed significant up-reglation of MDH2, Neurog1, and BDNF ( Prenatal morphine exposure leads to marked molecular and histopathological changes in the developing hippocampus, suggesting long-term risks for neurocognitive dysfunction. These findings emphasize the importance of limiting opioid use during pregnancy and identifying molecular targets for future therapeutic interventions. Show less

Microtubule organization plays a central role in cell differentiation, orchestrating essential processes such as cell polarization, mechanotransduction, organelle positioning and intracellular transport. A hallmark of many differentiated cells is the transition from a centrosomal to a non-centrosomal microtubule-organizing center (MTOC). Here, we demonstrate that both centrosomal and nuclear envelope (NE)-associated MTOCs coexist in osteoclasts. We show that the key players for NE-MTOC formation, the AKAP6 and nesprin-1 (SYNE1) isoforms AKAP6β and nesprin-1α, previously considered muscle specific, are upregulated during osteoclast differentiation, suggesting a conserved role in NE-MTOC assembly across cell types. Targeted depletion of AKAP6 in RAW264.7-derived osteoclasts led to the displacement of the Golgi and MTOC-associated proteins PCM1, pericentrin and CDK5RAP2 from the NE, while their centrosomal localization remained intact. This selectively impaired microtubule nucleation from the NE without disrupting centrosomal microtubule activity, enabling a functional dissection of the two MTOCs. Loss of NE-MTOC activity, through AKAP6 depletion, impaired podosome formation and significantly reduced bone resorption capacity, highlighting the distinct and essential role of NE-derived microtubules in osteoclast function. Show less

Insufficient physical activity is prevalent among perinatal women, and digital health interventions offer a promising avenue to promote engagement in physical activity within this population. However, previous studies have relied heavily on self-reported data, lacking a systematic synthesis based on objective measurements. This study aims to systematically evaluate the effects of digital health interventions on objectively measured physical activity and sedentary behavior in perinatal women. A systematic search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library databases from inception to December 20, 2025. Fourteen randomized controlled trials (RCTs) involving 2,101 participants were included. The Risk of Bias 2.0 (RoB 2.0) tool was used to assess bias risk, random-effects models were employed to pool effect sizes, and the quality of evidence was evaluated using the GRADE system. The meta-analysis showed that, following the exclusion of outliers via sensitivity analysis, digital health interventions significantly increased daily step counts (MD = 0.68, Digital health interventions can effectively and robustly enhance daily baseline activity levels in perinatal women, with the observed increments potentially reaching the minimal effective dose for improving metabolic health. However, current intervention designs face challenges in driving high-intensity behavior change and disrupting sedentary habits. Future research should explore more targeted and personalized intervention strategies. This systematic review and meta-analysis has been registered in PROSPERO (www.crd.york.ac.uk/prospero), identifier CRD420261280936. Show less

Recent work by Mu et al. identifying irisin as a modulator of adipose tissue IL-33 and regulatory T cells introduces a new paradigm in immunometabolic biology, shifting attention from thermogenesis alone toward immune-stromal crosstalk as a determinant of metabolic health. By inducing IL-33 production in adipose mesenchymal stromal cells, irisin preserves ST2+ regulatory T cells (Tregs) in visceral adipose tissue, thereby restraining inflammation, improving insulin sensitivity, and promoting metabolic homeostasis. This mechanism expands the concept of exercise-induced metabolic protection by highlighting adipose tissue immune niches as critical targets of myokine action. In parallel, emerging evidence from preclinical models indicates that irisin-driven IL-33 signaling in subcutaneous adipose tissue contributes to thermogenic activation through mechanisms distinct from Treg-mediated immune regulation, highlighting depot-specific effects of this pathway. Beyond adipose tissue, irisin has emerged as a pleiotropic mediator with reported roles in glucose homeostasis, cardiovascular protection, and neurobiology. Importantly, accumulating evidence indicates that irisin may also exert neuroprotective effects, including the induction of brain-derived neurotrophic factor (BDNF), amyloid-β (Aβ) clearance, and α-synuclein degradation, thereby linking metabolic and neurodegenerative pathways. Although the findings of Mu et al. derive from preclinical models, they provide a conceptual model for therapeutic strategies aimed at reproducing selected benefits of exercise in obesity, metabolic and neurodegenerative disorders. Notably, these effects appear to depend on sustained irisin exposure in preclinical systems, supporting a role for irisin as a regulator of long-term immunometabolic homeostasis. Collectively, these observations position the irisin/IL-33/Treg axis as a promising link between exercise, adipose tissue immunity, and systemic metabolic regulation, suggesting that targeting immunometabolic circuits, rather than energy balance alone, may open new avenues for future therapeutic intervention. Show less

Lipoprotein(a) [Lp(a)] has been recognized as a genetically determined and independent contributor to atherosclerotic cardiovascular disease. However, its role in lower extremity arterial disease (LEAD) among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains insufficiently studied. Given the overlapping metabolic disturbances in both conditions, such as insulin resistance and lipid abnormalities, a potential relationship between Lp(a) and peripheral vascular injury in MASLD is biologically plausible. This study aimed to investigate the cross-sectional association between circulating Lp(a) concentrations and the presence of LEAD in a well-characterized MASLD population. A total of 468 MASLD patients undergoing routine health check-ups were included. Lp(a) levels were stratified into three categories: <10 mg/dL, 10–30 mg/dL, and ≥ 30 mg/dL. LEAD was diagnosed using duplex ultrasonography. Multivariable logistic regression models were used to assess the relationship between Lp(a) levels and the presence of LEAD, with adjustments for demographic variables, metabolic conditions, and lipid-related parameters. Subgroup analyses were conducted to assess potential effect modification. LEAD was diagnosed in 61.5% ( Elevated Lp(a) levels were associated with a higher prevalence of LEAD in patients with MASLD. Although the magnitude of association per unit increase was modest, higher Lp(a) concentrations were associated with greater LEAD prevalence. These findings should be interpreted cautiously and viewed as hypothesis-generating, particularly with respect to subgroup analyses. Prospective studies are needed to clarify causality and clinical relevance. The online version contains supplementary material available at 10.1186/s12872-026-05600-7. Show less

Lipoprotein(a) [Lp(a)] is a novel biomarker for Atherosclerotic cardiovascular disease prediction. Yet, given the scarcity in high-quality evidence, its use in routine primary prevention screening is lacking. For this reason, we aimed to assess Lp(a) prognostic utility during routine screening. A retrospective cohort of adults with available Lp(a) measurement, taken during a screening program (2008-2024) in a tertiary care center. Major adverse cardiovascular events (MACE) was the study primary outcome. The optimal Lp(a) threshold was evaluated using spline curve analysis and validated by Cox regression models adjusted for clinical and laboratory covariates. Subgroup analyses were performed in patients with SCORE2 and PCE data. 3052 people were included with a median (IQR) follow-up of 6.4 (3.5-12) years. Lp(a) threshold of 50 mg/dL was identified as a risk inflection point. High Lp(a) (> 50 mg/dL) was associated with increased MACE risk, independent of clinical data (HR 1.55, 95% CI 1.10-2.17, p = 0.011) or different laboratory variables (HR 1.62, 95% CI 1.07-2.46). High Lp(a) remained a predictor for MACE in models incorporating the SCORE2 and PCE scores, and its incorporation into these scores improved their performance in high-risk patients. In people with cardiovascular comorbidities, the optimal Lp(a) threshold for MACE prediction was 61 mg/dL, while it was 48.4 mg/dL in those without (n = 2778). In a large ambulatory and mostly healthy cohort, Lp(a) showed a strong predictive utility for cardiovascular events. These findings support the integration of Lp(a) into primary cardiovascular risk assessment and role in guiding emerging targeted therapies. Show less

Chronic psychological stress drives neuroimmune crosstalk and accelerates atherosclerosis progression. Physical exercise confers broad health benefits and is associated with reduced inflammation. However, the exercise-mediated factors and mechanisms that mitigate stress-induced vascular inflammation remain unclear. Chronic restraint stress (CRS) and voluntary exercise models were established to investigate the role of exercise in neuroimmune crosstalk. RNA sequencing identified kinesin family member 4 (Kif4) as a key gene associated with the attenuation of stress-induced inflammatory responses in peripheral blood monocytes following exercise. Combined co-immunoprecipitation-mass spectrometry and membrane proteomics identified T cell-interacting activating receptors on myeloid cell 1 (TARM1) as the Kif4 cargo. The function of TARM1 was validated using an immobilized TARM1-Fc fusion protein. Brain-derived neurotrophic factor (BDNF), a key effector during exercise and stress, regulated the Kif4-TARM1 axis using recombinant BDNF (rBDNF) and the TrkB inhibitor ANA-12. Finally, exercise-mediated effects and mechanisms were examined in atherosclerotic CRS-exposed mouse models and in patients with coronary artery disease (CAD) experiencing high psychological stress. Physical exercise alleviated stress-induced neuroimmune crosstalk, reduced the proinflammatory CD11b Physical exercise alleviates stress-induced neuroimmune crosstalk through the BDNF-Kif4-TARM1 axis, revealing a novel neuroimmune-mediated brain-heart axis that supports exercise-based therapeutic strategies for psychogenic CAD. Chronic psychological stress drives systemic inflammation through neuroimmune mechanisms, thereby accelerating the progression of coronary artery disease (CAD). Physical exercise alleviates stress-induced neuroimmune crosstalk, partly by suppressing proinflammatory responses in monocytes/macrophages. This study provides novel insights into exercise-regulated neuroimmune mechanisms involving the monocyte BDNF-Kif4-TARM1 axis. In both an atherosclerotic mouse model and patients with CAD, exercise mitigated stress-induced inflammation via the BDNF-Kif4-TARM1 axis. Show less

Hypertriglyceridemia is a widely prevalent disorder of lipid metabolism that increases the risk of cardiovascular disease and pancreatitis, and it often remains difficult to control even with standard treatments. Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III (ApoC-III), offers a new and promising option for lowering triglyceride levels. A systematic search of PubMed, Scopus, Web of Science, and Cochrane was conducted through September 2025 to identify randomized controlled trials (RCTs) comparing olezarsen with placebo in adults with hypertriglyceridemia at high cardiovascular risk. Dichotomous outcomes were analysed as risk ratios (RRs) and continuous outcomes as percentage mean differences (MDs), both with 95% confidence intervals (CIs). Four RCTs (n = 1615 patients) were included. Olezarsen significantly reduced triglycerides (MD -47.71%, 95% CI -56.78 to -38.64, p < 0.0001), non-HDL-C (MD -22.11%, 95% CI -28.48 to -15.75, p < 0.0001), ApoC-III (MD -68.93%, 95% CI -77.54 to -60.31, p < 0.0001), VLDL-C (MD -48.52%, 95% CI -57.16 to -39.87, p < 0.0001), and ApoB (MD -10.67%, 95% CI -16.83 to -4.51, p = 0.0007), while increasing HDL-C (MD 35.13%, 95% CI -27.30 to -42.96, p < 0.0001). LDL-C showed no significant change. The risks of any or serious adverse events were comparable to placebo. Olezarsen was associated with fewer acute pancreatitis events (p = 0.035) but higher rates of liver enzyme elevations ≥ 3× ULN (p = 0.046). Olezarsen demonstrated consistent improvements in triglycerides and other atherogenic lipid parameters with an overall acceptable safety profile. These findings suggest that olezarsen may be a useful adjunct option for patients with persistent hypertriglyceridemia despite standard therapy. Further large-scale and long-term studies are needed to confirm its cardiovascular and safety outcomes. Show less

This study was designed to investigate the effect of 6-gingerol-rich extract of ginger (6-GIRPOG) on oxidative stress, inflammation and neurotransmission in chronic unpredicted mild stress (CUMS)-induced depressed male Wistar rats. Twenty-five (25) male Wistar rats in total were divided into five groups at random (n = 5 in each group). The control group received 0.5 ml of normal saline, CUMS rats were only exposed to CUMS daily, CUMS + fluoxetine rats were exposed to CUMS and orally received 10 mg/kg per body weight of fluoxetine daily, CUMS + 6-GIRPOG (100) and CUMS + 6-GIRPOG (200) rats were exposed to CUMS and orally received 100 and 200 mg/kg body weight of 6-GIRPOG respectively (daily). Exposure to CUMS and treatment were carried out for a period of 21 days, after which light and dark box test, sucrose splash test, and forced swim test were conducted to assess the behavioral functions. The rats were then euthanized and their brain samples were collected for biochemical analysis. The exposure to CUMS caused behavioral alterations as well as a significant (p<0.05) decrease in the levels of brain-derived neurotrophic factor (BDNF), glutamate, reduced glutathione (GSH), and activities of superoxide dismutase (SOD). Furthermore, the exposure to CUMS caused a statistically significant rise (p<0.05) in the brain norepinephrine, cortisol, nuclear factor kappa-B (NFK-B), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6. However, the administration of both 100 and 200 mg/kg of 6-GIRPOG effectively reversed these behavioral and biochemical changes. Consequently, the study reveals the role of 6-GIRPOG in ameliorating CUMS-induced depression and brain damage via antioxidative, anti-inflammatory, and neurotransmission modulatory mechanisms. Show less

This study investigated the therapeutic potential of exercise training and the associated role of Glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1) in an experimental Alzheimer’s disease (AD) model. Using a D-galactose/AlCl [Image: see text] Show less

The prevalence of Type 2 diabetes mellitus (T2DM) is rapidly increasing in India, yet molecular markers that reflect early disease susceptibility remain limited. Epigenetic modifications such as DNA methylation may reflect early metabolic vulnerability preceding overt dysglycemia. In this study, we examined genome-wide DNA methylation patterns in a pilot subset nested within a prospective Indian cohort using Nanopore sequencing and assessed their associations with previously identified metabolite predictors from the same cohort. Genome-wide DNA methylation profiling was performed on buffy-coat DNA from 12 participants who were normoglycemic at baseline and later classified into normoglycemia, prediabetes, or T2DM based on their glycemic status at 6-year follow-up. At baseline, gene-level aggregation of CpG methylation revealed directionally consistent hypermethylation of seven genes (ABCG1, ADARB2, BCL2, DLC1, EGFLAM, SYK, ZNF516) in individuals who later developed T2DM, while those progressing to prediabetes exhibited six hypermethylated (ABCG1, FLT3, LCP1, MBP, NCOA2, TCF7L2) and five hypomethylated genes (ZFHX3, PAX6, PTPRN2, ERC1, HIPK1). ABCG1 showed consistent hypermethylation across both groups. Longitudinal within-individual comparisons identified additional gene-associated methylation changes, including ANK1, IQSEC1, and RUNX1, and shared alterations in CACNA1C, KANSL1, PTPRN2, and TTC34, while six genes showed stage-dependent directional shifts in methylation (ASB3, EFR3A, PCSK5, KLHL14, PDE4C, UNC5C). Correlation analyses at baseline suggested associations between ABCG1 and EGFLAM methylation, fasting glucose, phosphatidylethanolamine [PE (20:3₁₈:0)] and insulin sensitivity indices. This pilot longitudinal study suggests that gene-associated DNA methylation changes in blood may be detectable prior to the onset of dysglycemia. These findings are exploratory and hypothesis-generating, highlighting candidate genes and epigenetic-metabolic associations for targeted validation in larger, independent cohorts using alternative analytical approaches. Show less

Negative Emotional symptoms such as depression and anxiety do not exist independently, often co-occurring in the same individual, and heterogeneity exists between individuals suffering from depression and anxiety; however, prior research has rarely investigated heterogeneity in a person-centered manner and from the perspective of college students. The main purpose of this study was to explore this heterogeneity and its association with e-Health literacy (e-HL) using Latent profile analysis (LPA), a person-centered statistical method. A total of 7,503 Chinese college students from 10 regions (including Guangdong Province, Shanghai Municipality, and Jiangsu Province) were surveyed using the Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire (PHQ-9) to assess anxiety and depressive symptoms. LPA was employed to identify potential profiles of negative emotional symptoms and validate their robustness; binary logistic regression was used to explore differences in demographic characteristics (sex, grade ranking), sociological factors (family residential background, per capita monthly family income), and lifestyle factors (adherence to physical activity, smoking status, alcohol consumption) across profiles; analysis of variance (ANOVA) was applied to compare e-HL levels among different profiles. The two-class model was identified as the optimal classification of negative emotional symptoms: low/no negative emotional symptoms (61.49%) and high negative emotional symptoms (38.51%). Female college students, those with low per capita monthly family income, lack of regular physical exercise, and alcohol consumption habits were more likely to be categorized into the high negative emotional symptoms group (all Reliance on self-report measures may lead to recall bias and social desirability bias; the cross-sectional design cannot establish causal relationships between variables; digital addiction, a potential confounding factor that may co-occur with negative emotional symptoms and influence e-HL, was not included in the analysis. This study identified two distinct latent profiles of negative emotional symptoms among Chinese college students and their key predictive factors using LPA. The findings highlight the need for stratified early screening for high-risk groups (females, low-income families, inactive individuals, and drinkers) and the development of targeted interventions. Enhancing e-HL could be a potential pathway to improve mental health outcomes, providing actionable insights for scientific and effective mental health management in colleges and universities. Show less

Tau neurofibrillary tangles are a hallmark of several neurodegenerative diseases called tauopathies, including frontotemporal dementia and Alzheimer's Disease. Ongoing clinical trials for tauopathies seek to reduce Tau in the brain through immunotherapy, antisense oligonucleotides, and siRNA. Show less

Stress plays a pivotal role in anxiety-like disorders and cognitive decline. The present study investigated the potential effects of prior royal jelly supplementation and environmental enrichment against stress-induced anxiety-like behaviors, serum corticosterone, hippocampal brain-derived neurotrophic factor (BDNF) levels, and cognitive performance deficits in stressed rats. Male Wistar rats were randomly devised into 8 experimental groups. Rats were subjected to royal jelly (200 mg/kg) via oral gavage, standard environmental enrichment, or combination all for 14 days and control rats received saline in the same period of time. Stress induction was done on the 7th day of treatments by exposure to the restrainer under 10°C. Then open field, elevated plus maze, and inhibitory passive avoidance memory tests were used to explore emotional-cognitive behaviour. Also, corticosterone levels, and hippocampal BDNF expression were measured. Stress resulted in an increase in the serum corticosterone levels, anxiety-like behaviors, and decreased hippocampal BDNF expression which reversed by environmental enrichment and royal jelly treatments. Remarkably, the combined treatment exerts a more pronounced effect on the aforementioned outcomes. Our study strongly proposes a novel emerging therapeutic approach through nutritional interventions, emphasizing the potential of these treatments to mitigate stress-induced anxiety and memory impairments prior to stress exposure. Show less

Friedreich's Ataxia (FRDA) is an early onset hereditary disorder with a strong neurodegenerative component caused by repeat expansions on the gene encoding for frataxin (FXN) that result in FXN deficiency. This deficit has been linked to a cascade of biochemical alterations, including mitochondrial dysfunction, oxidative stress and neuronal apoptosis, that drives the neurodegenerative process. FRDA is a very incapacitating disease and patients rely on very limited therapeutic alternatives, such as the recently approved drug omaveloxolone, to treat the oxidative stress. Nevertheless, previous studies have suggested the activation of the brain-derived neurotrophic factor (BDNF) may be a promising treatment to regulate FRDA pathophysiology. Herein, we characterize the effects of FXN deficiency in an in vitro model of primary cerebellar granule neurons (CGNs) derived from the FRDA mouse model YG8-800, as well as the therapeutic potential of BDNF partial agonism by the small molecule 7,8-dihydroxyflavone (7,8-DHF). We found evidence of mitochondrial dysfunction concomitant with DNA damage and enhanced cell death due to FXN deficiency in cultured neurons. The treatment with 7,8-DHF was able to reduce the markers of genotoxicity and apoptosis, without restoring the impaired mitochondrial function nor the total cell death, possibly through ferroptosis, revealing a partial neuroprotective effect insufficient to halt the neurodegenerative process in this in vitro model of FRDA. Show less

Mitochondrial dysfunction, oxidative stress, and neuroinflammation play a critical role in the occurrence and progression of Alzheimer's disease (AD). MicroRNAs (miRNAs) have been studied recently as potential therapeutic approaches for AD. In this study, we examined the function and underlying mechanism of microRNA-25802 (miR-25802), a newly discovered miRNA in an AD model. In order to evaluate the levels of oxidative stress, mitochondrial damage and neuroinflammation in neuroblastoma cells, four experimental groups were created: control group (neuroblastoma cells, SH-SY5Y), amyloid beta (Aβ)-induced neuroblastoma cells (SY5Y-Aβ), small extracellular vesicles (sEVs)-only group and miR-25802-loaded small extracellular vesicles (sEV-miR25802) administered group. Neuroinflammation, oxidative stress, mitochondrial damage, tau hyperphosphorylation, and Aβ accumulation were evaluated in Aβ-induced neuroblastoma cells. Oxidative stress was analyzed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase 1 (GPX1). Inflammatory markers such as tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule 1 (ICAM1), and brain-derived neurotrophic factor (BDNF) mRNA levels, a neurotrophic factor, were evaluated by RT-qPCR. Neurofilament light chain (NfL), vascular endothelial growth factor-A (VEGF-A), macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein-1 (MCP-1) and cytochrome c (Cyt-c), mitochondrial transcription factor A (TFAM), PTEN-induced kinase 1 (PINK1) and dynamin-1-like protein (DNM1L) protein levels were determined by ELISA. Mechanistically, sEV-miR25802 were shown to provide anti-inflammatory and neuroprotective effects by regulating neuroinflammation, mitochondrial dysfunction, and oxidative stress. These findings reveal the regulatory role of miR-25802 on neuroinflammation, mitochondrial damage, and oxidative stress and suggest that it may be a potential therapeutic target for AD. Show less

Brain-derived neurotrophic factor (BDNF) is considered to participate in regulating the endometriosis (EM) process. However, other functions and mechanisms of BDNF in EM progression still need to be further studied. Ectopic/normal endometrial stromal cells (ESCs) were isolated from EM tissues/normal control endometrial tissues. BDNF mRNA expression in EM tissues and normal control endometrial tissues was analyzed through quantitative real-time polymerase chain reaction. The protein levels of BDNF and glucose transporter 1 (GLUT1) were detected by Western blot. The function of ESCs was determined through cell counting kit 8 assay, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, Transwell assay, and wound healing assay. The interaction between BDNF and GLUT1 was assessed through a co-immunoprecipitation assay and immunofluorescence staining. BDNF expression was elevated in EM tissues and ectopic ESCs. Functional experiments revealed that BDNF knockdown repressed ectopic ESC proliferation, invasion, migration, and glycolysis and promoted apoptosis. In terms of mechanism, BDNF interacted with GLUT1 to enhance its protein expression. In addition, the repressing effect of BDNF knockdown on ectopic ESCs' growth, invasion, migration, and glycolysis was abolished by GLUT1 overexpression. Our study showed that BDNF could facilitate ectopic ESC function by interacting with GLUT1, thereby providing basic information for finding an effective therapeutic target of EM. Show less

Chronic ketamine exposure results in psychotic and cognitive symptoms that resemble those found in patients with schizophrenia. Emerging evidence suggests that patients with schizophrenia exhibit gut microbiota dysbiosis and decreased levels of short-chain fatty acids (SCFAs) and BDNF, which are related to the severity of psychotic and cognitive symptoms. Dietary inulin can regulate gut microbiota, SCFAs, and BDNF. However, the role of gut microbiota, SCFAs, and BDNF in chronic ketamine-induced schizophrenia-like behaviors is unclear. In this study, we found that chronic ketamine exposure for 28 days caused gut microbiota dysregulation, reduced the expression of SCFAs in serum, hippocampus, and feces, elevated gut permeability, downregulated the BDNF-TrkB-ERK1/2-CREB signaling pathway, caused neuronal damage, and decreased the expression of synaptic proteins Syn and PSD-95, which may lead to anxiety-like behaviors, prepulse inhibition (PPI) deficits, and spatial learning and memory deficits. In addition, inulin intervention reversed gut microbiota dysbiosis by decreasing the abundance of Show less

Depression is a multifactorial, chronic disorder and represents a leading cause of disability, with women exhibiting nearly twice the lifetime prevalence compared to men. Growing evidence indicates that this disparity cannot be explained by hormonal or psychosocial factors, but rather by dynamic interactions between environmental exposures, neuroendocrine signaling, and epigenetic regulation across development. This mini-narrative review aimed to examine how sex-specific exposome components interact with epigenetic mechanisms and synaptic remodeling processes to influence vulnerability to Major Depressive Disorder in women. The reviewed evidence demonstrates that fluctuations in ovarian hormones modulate HPA axis responsivity, neuroinflammatory signaling, and glutamatergic transmission through epigenetic regulation of stress-responsive genes such as Show less

Aortic valve disease (AVD) is a cardiovascular disorder highly prevalent in the elderly population. Aortic valve leaflets suffer hardening due to extracellular matrix (ECM) remodeling and subsequent calcification, leading to impaired blood flow and aortic valve stenosis. Valve interstitial cells (VICs) are fibroblast-like cells that can undergo myofibroblast activation and osteogenic transformation, contributing to disease progression. We performed a bioinformatic re-analysis of a publicly available scRNA-seq dataset to identify pathogenic VIC subpopulations and characterize cell-cell communication networks relevant to early AVD. Re-analysis of scRNA-seq data from aortic valves of These findings suggests the presence of a disease-associated VIC Spp1 Show less

Drug-induced hyperpigmentation (DIH) represents a significant subset of acquired pigmentation disorders and poses diagnostic challenges due to delayed onset and polypharmacy. This systematic review and meta-analysis aimed to identify medications significantly associated with DIH and evaluate their reported incidence. A systematic search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library for studies published between 2002 and June 2024. Eligible studies reported DIH as an outcome with incidence or descriptive data. Pooled proportions were calculated using a random-effects model, and heterogeneity was assessed via the I Twenty-two studies met the inclusion criteria. The overall pooled incidence of DIH was 36.7% (95% CI: 0.291-0.444). Subgroup analyses revealed the highest incidences with tyrosine kinase inhibitors (89.2%) and MC4R agonists (71.4%), followed by antibiotics (52.0%), antineoplastic agents (35.5%), and antimalarials (29.0%). Commonly implicated agents included minocycline, hydroxychloroquine, and hydroxyurea. DIH is a prevalent adverse drug reaction with considerable variation in incidence across drug classes. Recognition of high-risk medications is essential for prompt diagnosis and clinical management. The study protocol was pre-registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42024529250). Show less

We investigated the relationship between cerebrospinal fluid (CSF) and plasma biomarkers of inflammation, neurodegeneration, and neurocognitive performance in people with HIV (PWH), using longitudinal samples from two previously published cohorts: ACTG A5090 (virally suppressed on antiretroviral therapy, ART) and A736 (ART-naïve or failing). We analyzed paired CSF and plasma samples, as well as 7-domain standardized neurocognitive test scores, at baseline and 24 weeks. Biomarkers included markers of inflammation (e.g., TNF-α, IL-6, IP-10) and neurodegeneration (e.g., NFL, p-Tau217, Aβ42), which were quantified via high-sensitivity immunoassays. Associations with cognition were tested using regression, mediation, and interaction models. Cross-sectional analyses revealed nominal associations between inflammatory markers and cognitive performance, with plasma IL-6 and IP-10 at baseline, and CSF TNFα at week 24 showing the strongest correlations (p < 0.05, uncorrected); however, none survived correction for multiple comparisons. Conversely, higher CSF Aβ42 and plasma BDNF were positively associated with memory and executive function. Longitudinally, biomarker changes did not significantly predict change in global cognition (ΔNPZ-8); the strongest trend (p-Tau217, ρ = -0.12, p = 0.38) was not statistically significant, and multivariate models failed to identify robust predictors (R These results suggest a potential role of CSF TNFα in mediating the neurocognitive effects of HIV and highlight compartment-specific inflammatory dynamics. Plasma TNFα, GFAP, and NFL may serve as peripheral indicators of CNS pathology, though with only moderate concordance. Astrocyte-tau interactions require cautious interpretation pending replication in larger cohorts. Show less

Numerous genetic variants have been identified by genome-wide association studies as being associated with colorectal cancer (CRC) risk. Metabolome-wide association analysis was performed for 187 CRC-associated genetic variants using genomic data and untargeted Show less

Since breast milk provides essential nutrients and bioactive compounds, such as adipokines and growth factors, which are indispensable for neonatal growth and metabolic regulation, this review seeks to elucidate the differences in these bioactive components between preterm and term breast milk and to evaluate their potential influence on neonatal development. Adipokines such as leptin, adiponectin, resistin, ghrelin, and visfatin, alongside growth factors including epidermal growth factor, insulin-like growth factor, and brain-derived neurotrophic factor, exhibit variable concentrations in preterm versus term milk. Preterm milk generally contains higher levels, potentially reflecting an adaptive response to support accelerated growth. However, findings are inconsistent across studies, likely due to differences in study design, timing of milk collection, analytical methods, and variability in maternal characteristics. Variations in bioactive component profiles between preterm and term milk suggest compensatory mechanisms in preterm lactation. Further longitudinal studies are warranted to clarify these relationships and to elucidate the long-term effects of breast milk adipokines and growth factors on preterm infant growth and metabolic programming. Show less

Neuroinflammation is a chronic inflammatory response that contributes to synaptic dysfunction and neuronal damage, it is a common feature among various neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD). Tocotrienol-rich fraction (TRF) is a form of vitamin E that is known for its anti-inflammatory, antioxidant and neuroprotective properties. Yet, it has not been adequately investigated in both cellular and animal neuroinflammation models. In this study, the potential therapeutic effects of TRF were investigated in-vitro using BV2 microglial cells and also in-vivo in a pilot study using Sprague Dawley rats. TRF at 5 and 10 µg/mL were found to reduce nitric oxide (NO) and reactive oxygen species (ROS) levels. Furthermore, in-vivo treatment with TRF significantly increases the recognition index implying improvement in cognition ability. Gene expression analysis showed downregulation of RelA, TNF-α and IL-6 while NFE2L2 and BDNF were upregulated. These findings suggests that TRF may help mitigates neuroinflammation and oxidative stress, indicating its potential as a candidature for further investigation in neurodegenerative diseases associated with chronic neuroinflammation. Show less

Plasma phosphorylated tau217 (p-tau217) is a promising biomarker for Alzheimer's disease (AD) risk detection. Its relationship with brain microstructure and cognitive impairment remains unclear. Multi-component T2-relaxometry is an MRI technique sensitive to myelin content, axonal degeneration, and neuroinflammation. A total of 229 participants classified by p-tau217 levels into p-tau217- ( The p-tau217+ participants showed poorer cognition, increases in FQFWF and TWC, and reductions in IEWF and T2 High p-tau217 level associates with brain microstructure alterations and poorer cognition, supporting it as a biomarker of AD-related neuropathology and the utility of T2-relaxometry for detecting tissue integrity. Show less