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As a result of individual genetic variations, some patients show no response to initial antidepressant medications. This study aims to investigate the association between specific genetic polymorphisms and the efficacy of antidepressant drugs and to improve the accuracy and effectiveness of treatment under the guidance of genetic testing. A retrospective screening was conducted on medical records from, Suixian People's Hospital between January 2022 and December 2024. A total 202 patients with depression carrying the CYP2C19 gene were selected after the application of exclusion criteria. They were assigned to three groups in accordance with their genetic metabolism types: the rapid metabolism group (Group A, n = 65), the intermediate metabolism group (Group B, n = 94) and the poor metabolism group (Group C, n = 43). All three groups were treated with sertraline for a six-week treatment cycle. The observation indicators included scores on the Hamilton Depression Scale (HAMD); onset time of drug effect; rates of response and remission; scores on the Clinical Global Impression-Improvement (CGI-I) scale; levels of the neurotransmitter factors 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA) and brain-derived neurotrophic factor (BDNF); incidence of adverse events; and scores on the Morisky Medication Adherence Scale-8 (MMAS-8). The baseline data of the three groups of patients were comparable before medication (p > 0.05). Compared with those in Groups A and B, patients in Group C showed a significantly greater reduction in HAMD scores (all p < 0.05), along with higher response rates (all p < 0.05) and remission rates (all p < 0.05). Amongst the three groups, Group C had a shorter onset time of drug effect (all p < 0.05); more significant improvement in CGI-I scores (all p < 0.05); and more prominent upregulation of neurotransmitter factors, namely, 5-HT (all p < 0.05), GABA (all p < 0.05) and BDNF (all p < 0.05). Regarding the incidence of adverse events, Group C had the highest rate, whereas Group A had the lowest (10.8% vs. 24.5% vs. 41.9%). Compared with other groups, Group B exhibited a more significant increase in MMAS-8 scores (all p < 0.05). Metabolic phenotype exerts substantial effects on the therapeutic outcome of sertraline in patients with depression carrying the CYP2C19 gene. Amongst groups, Group C showed better therapeutic efficacy but an elevated incidence of adverse events and lower medication adherence; Group A had relatively poor efficacy; and Group B demonstrated superior adherence. In clinical practice, individualised treatment can be implemented on the basis of CYP2C19 metabolic typing to improve therapeutic efficacy and reduce adverse events and medical burden. Show less

The study explores the interconnection between the latent categories of mobile phone dependency and self-control in the sub-healthy urban older adults practicing Tai Chi. The findings aim to provide a reference for preventing mobile phone dependence, enhancing self-control and improving sub-health status in this population. A multi-stage cluster sampling method was employed to screen 560 sub-healthy urban older adults from 2,946 valid survey responses in Xuzhou City, Jiangsu Province. Sub-health status was verified using the SHMS V1.0 scale. Data were collected between September and October 2025. Latent profile analysis (LPA) was used to categorize mobile phone dependency and self-control. Pearson correlation analysis measured the relationship between these two variables. Additionally, chi-square test examined demographic differences across the identified latent profiles. Finally, multivariate logistic regression analyzed the associations between mobile phone dependency, self-control, and Tai Chi exercise. LPA identified four distinct profiles: Low dependency-Medium control (109 individuals, 19.5%), High dependency-No control (207 individuals, 37.0%), No dependency-High control (191 individuals, 34.1%), and Moderate dependency-Low control (53 individuals, 9.5%). These categories had statistically significant differences ( Tai Chi exercise exerts differential effects on urban sub-healthy older adults across distinct latent profiles of mobile phone dependency and self-control. Societal stakeholders should strengthen Tai Chi programs for these diverse categories to promote their physical and mental wellbeing. Show less

The large-scale development of pig farming has introduced significant stressors that negatively affect pigs' mental health, behavior, and production efficiency. The hippocampus, crucial for cognition and stress response regulation, plays a central role in these processes. However, the regulatory mechanisms underlying hippocampal function across pig breeds with different domestication statuses and their implications for behavior and breeding strategies remain unclear. We performed single-nucleus RNA sequencing (snRNA-seq) on hippocampal tissues from 22,342 cells across three pig breeds: Asian wild boar, Jinhua, and Duroc, representing different domestication statuses. We identified six major hippocampal cell types and annotated 108 breed-specific transcription factors, including GATA2, SPI1, and EBF1. Additionally, we characterized 83 co-expression modules and 50 significant ligand-receptor pairs, such as TGFβ, WNT, and SPP1, revealing complex intercellular communication networks. Oligodendrocyte expression patterns were conserved across all breeds. We identified 194 candidate genes linked to stress resilience, mental health, and feeding behavior, including MC4R, RYR2, PDE10A, and ABCG2. Alzheimer's disease-related gene enrichment was lower in Duroc pigs, consistent with reduced APOE expression. We also developed the Pig Hippocampus Single-cell Atlas (PHiSA, http://alphaindex.zju.edu.cn:8503/ ), an open-access database allowing breed-specific hippocampal analyses and validation of gene expression at the single-nucleus level. This study offers insights into hippocampal function regulation in pigs, focusing on stress resilience, behavior, and productivity. It highlights conserved and breed-specific molecular features of hippocampal cell types and their roles in adaptability and mental health. By integrating single-nucleus data, the research suggests that genetic strategies could be used to improve animal welfare, stress management, and production efficiency in pig breeding programs. Show less

At present, the research on the effective teaching behaviors of clinical nursing teachers mainly focuses on the overall level of effective teaching behaviors and their relationship with other variables, ignoring the individual heterogeneity of the effective teaching behaviors of clinical nursing teachers. This study through latent profile analysis (LPA), aims to identify different effective teaching behavior profiles of clinical nursing teachers and explore the demographic and personal factors associated with these different effective teaching behavior profiles. This is a cross-sectional study. A survey was conducted among 842 clinical nursing teachers through demographic questionnaires, the Effective Teaching Behavior Scale, and the Self-Efficacy Scale. LPA analyzes the potential characteristics of effective teaching behaviors of clinical nursing teachers. The multiple logistic regression method was used to explore the predictors of different spectra. Three potential characteristics were identified: Profile 1- high effective teaching behavior group, Profile 2- moderate effective teaching behavior group, and Profile 3 - low effective teaching behavior group. Marital status, years of teaching experience and self-efficacy are predictive factors for different profiles. Most clinical nursing teachers are classified as type 1, and they have relatively good effective teaching behavior ability. Strategies such as enhancing self-efficacy, paying attention to the marital status of clinical nursing teachers, and focusing on training clinical nursing teachers with shorter tenure may be effective ways to improve the effective teaching behaviors of clinical nursing teachers in different situations. Show less

Neuroplasticity, the brain's capacity to adapt and reorganize in response to experiences and environmental changes, is fundamental to cognitive aging. As individuals age, cognitive functions such as memory, processing speed, and executive function commonly decline, driven largely by changes in neuroplasticity mechanisms like synaptic plasticity, neurogenesis, and functional reorganization. Synaptic plasticity is a well-established mechanism supporting learning and memory across the lifespan, whereas adult neurogenesis, robustly demonstrated in rodents, remains highly limited and controversial in the adult and aged human brain, with evidence largely restricted to rare post-mortem observations and injury-associated conditions. Functional reorganization allows the brain to adapt to structural changes, helping to preserve cognitive function despite age-related decline. Several factors, including oxidative stress, neuroinflammation, and hormonal shifts, exacerbate the decline in neuroplasticity, accelerating cognitive deterioration. Various interventions, including cognitive training, physical exercise, and pharmacological approaches, have demonstrated the potential to promote neuroplasticity and support cognitive health in aging populations. However, one of the major challenges is tailoring these interventions to the unique needs of individuals, as well as identifying novel therapeutic targets for intervention. To effectively address the cognitive decline associated with aging, future research should focus on developing personalized strategies and innovative techniques to enhance or modulate specific neuroplasticity-related processes under defined conditions in the aging brain. These advancements may provide better tools for delaying, mitigating, or even reversing age-related cognitive decline, improving quality of life for older individuals. Show less

Niemann-Pick disease, type C1 (NPC1), is a rare, fatal, neurodegenerative lysosomal disorder caused by pathological variants in Proximal Extension Assays (PEA) were used to determine relative protein expression levels from 68 serum samples from NPC1 individuals and 20 age-appropriate control serum samples. Statistical models identified NPC1 disease-specific effects after adjusting for covariates. Selected proteins were orthogonally validated by ELISA and correlated with assessments of both disease severity (Age of Neurological Onset (ANO) and Annual Severity Increment Score (ASIS)) and disease burden (NPC Neurological Severity Score (NSS). Quantifiable data was obtained on 2888 proteins, revealing 186 increased (adjusted log The statistical analysis pipeline developed in this study is flexible and scalable and supports application to high-dimensional proteomic datasets. This study identified and validated serum proteins with altered expression in individuals with NPC1, responded to miglustat therapy, and correlated with disease severity or burden. These proteins may have clinical utility as biomarkers and provide insights into cellular mechanisms contributing to NPC1 disease pathology. NCT00344331 (Registration on 2006-06-23). Show less

Previous research has indicated the brain-derived neurotrophic factor (BDNF) level is lower in schizophrenia and associated with cognitive impairment. Irisin-BDNF axis may strengthen learning and memory functions. This study examined associations between BDNF, peroxisome proliferator-activated receptor-gamma (PPAR gamma) and irisin with cognitive deficits in schizophrenia. We enrolled 80 patients with schizophrenia and 80 healthy controls (HCs). The enzyme-linked immunosorbent assay (ELISA) method was used for biochemical analysis. The Stroop Test, Trail Making Test (TMT), and Verbal Fluency Test (VFT) were used for cognitive assessment. Statistical analyses included t-tests, correlations, and analysis of covariance (ANCOVA) controlling key confounders. In unadjusted analyses, patients had significantly lower BDNF and PPARγ levels than HCs (ps < 0.001). After controlling for covariates, the difference in BDNF was still significant (F = 11804.71, BDNF demonstrates the most robust association with schizophrenia and cognitive function. The association of PPARγ with schizophrenia is confounded by demographic and metabolic factors, and irisin showed a limited link only to negative symptoms. Not applicable. Show less

Lipoprotein(a) [Lp(a)] is a causal, genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS). Although elevated Lp(a) affects approximately 20% of the global population, specific pharmacological options have long been unavailable, leaving a major gap in residual risk management. This review synthesizes current understanding of Lp(a) molecular architecture, genetics, and metabolism, and integrates mechanistic evidence linking Lp(a) to pro-atherogenic, pro-inflammatory, and pro-thrombotic pathways. We summarize epidemiological and genetic data associating Lp(a) with a broad spectrum of cardiovascular outcomes and discuss current clinical guidelines on screening and risk stratification. Furthermore, we provide an up-to-date overview of the emerging therapeutic landscape, including RNA-targeted therapies and novel oral small molecules. With pivotal phase 3 outcome trials nearing completion, the field is transitioning from viewing Lp(a) as an untreatable biomarker to an actionable therapeutic target, with important implications for precision cardiovascular prevention. Show less

(1) Background: The increasing environmental concentration of polystyrene nanoplastics (PS-NPs) may pose a risk of human exposure and health threats. Previous studies have demonstrated that exposure to PS-NPs poses a threat to neural synaptic plasticity, yet the underlying mechanisms remain unclear. (2) Methods: Hippocampal astrocytes and neurons were co-cultured, exposed to PS-NPs at concentrations of 10, 50, and 100 μg/mL, and cytotoxicity was assessed. We investigated PS-NP-induced impairment of synaptic plasticity by regulating the brain-derived neurotrophic factor (BDNF). (3) Results: Calmodulin-dependent protein kinase II (CaMKII) is a central molecular organizer of synaptic plasticity, learning, and memory, and its activity is intrinsically linked to intracellular calcium ion concentration. Our research indicates that PS-NPs may interfere with calcium ion signaling and CaMKIIα activity, thereby reducing CaMKIIα activity. This subsequently downregulates the expression of cAMP response element-binding protein (CREB), modulates BDNF expression, and impacts synaptic plasticity. (4) Conclusions: In summary, this study primarily focused on the effects of PS-NPs exposure on hippocampal synaptic plasticity. Show less

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments, and repetitive and aggressive behaviors. The pathophysiology of ASD still remains unclear, while the population with ASD is 1/36 in children in the USA in 2024. Evidence suggests a wide range of inconsistent changes in brain-derived neurotrophic factor (BDNF), the most important neurotrophin in the central nervous system, in ASD. The present systematic review investigated studies that examined BDNF levels in three main ASD-like models in rodents [induced by valproic acid (VPA) and propionic acid (PPA), and in the BTBR mouse strain] in accord with PRISMA guidelines and in PubMed database. Forty-two studies were included. Most studies used male rats/mice. The results showed ASD model induced by VPA often leads to decreased BDNF, although unchanged or increased BDNF levels were also reported. ASD model induced by PPA leads to both increased and decreased BDNF. BDNF changes in BTBR mouse strain were also inconsistent. We found that the type of molecular assay appears to be important in evaluating BDNF. Also, few evidence showed a role for postnatal day and sex difference in BDNF changes in ASD-like rodent models. In addition, some studies have shown the potential role of the brain region in BDNF changes in different ASD-like models. In conclusion, it was suggested that inconsistencies in BDNF changes in rodent models of ASD may be related to the type of the molecular assay, the brain region, ASD model, sex, or even the postnatal day. However, evidence is still insufficient. Show less

Findings of previous studies on associations between dairy consumption and metabolic health status were inconsistent. This study aimed to assess the link between consumption of dairy foods and metabolic health status, brain-derived neurotrophic factor (BDNF) and adropin levels in adults. Cross-sectional. An observational study in Isfahan, Iran. Adults (n=527) selected by multistage cluster random sampling. Dietary intakes were assessed via a validated 168-item food frequency questionnaire. Anthropometric indices, blood pressure and biochemical parameters were assessed. The criteria proposed by Wildman Participants had a mean age of 42.66 years (45.7% women). Moderate consumption of total dairy was, respectively, linked to 58% lower odds of MU (OR Moderate consumption of total and low-fat dairy was associated with lower odds of being metabolically unhealthy in Iranian adults, but high-fat dairy intake was not. Hypertension was less common among individuals with higher dairy intake. No association was found between dairy intake and serum levels of BDNF or adropin. Show less

Western diet (WD) fed Melanocortin 4 receptor-knockout (MC4R-KO) mice develop a phenotype resembling human metabolic dysfunction-associated steatohepatitis (MASH). Despite its clinical relevance, the role of the gut–liver axis in MASH pathogenesis remains unclear. We investigated the gut-liver axis through microbiomic and metabolomic analyses of WD-fed MC4R-KO mice, and we examined their association with MASH pathology. We performed an integrated microbiome and metabolome analysis of the liver, small intestinal contents, large intestinal contents, and plasma of wild-type (WT) and MC4R-KO mice fed either a normal diet or WD. Markers of hepatic inflammation, fibrosis, and steatosis measured in this study were used to assess MASH severity and to correlate microbiome and metabolite alterations. WD-fed MC4R-KO mice exhibited significant hepatic steatosis, inflammation, and fibrosis. The abundance of certain microbiota, including Muribaculaceae and The observed gut microbial and metabolic alterations, particularly bile acid and lipid metabolism dysregulation, offer insights into potential therapeutic targets aimed at modulating the gut–liver axis to treat or prevent MASH. The online version contains supplementary material available at 10.1186/s13099-026-00813-9. Show less

Endoplasmic reticulum (ER) stress plays a significant role in chronic pain, but its potential involvement in chronic itch remains largely unexplored and poorly understood. In the current study, we investigated whether ER stress signaling in keratinocytes contributes to the pathogenesis of chronic itch. Our behavioral tests showed that the ER stress inhibitor 4-PBA attenuated itch-related behaviors in both acute and chronic itching mouse models, and reduced compound 48/80 and serotonin-induced activity of dorsal root ganglion (DRG) neurons. qPCR and western blotting revealed that the ER stress-related proteins and Lipocalin-2 (LCN2) were significantly elevated in the affected skin under chronic itch conditions and in cultured keratinocyte HaCaT cells and mice skin keratinocytes. The ELISA test showed that the level of LCN2 increased significantly in plasma but not in DRG tissue, from both acetone-ether-water (AEW) induced dry skin and imiquimod (IMQ) induced psoriasis model mice. Current clamp recording demonstrated that LCN2 induced hyperexcitability in dorsal root ganglia neurons, which could be abolished by HS024, the inhibitor of melanocortin receptor 4 (MC4R). In addition, pharmacological inhibition of transient receptor potential vanilloid 1 (TRPV1) or TRPV1 knockout blocked LCN2-induced hyperexcitability in DRG neurons. In conclusion, this study demonstrated that keratinocyte ER stress is involved in chronic itch genesis by releasing LCN2, which sensitized primary sensory neurons via TRPV1. These findings suggested that inhibition of ER stress in keratinocytes could be a promising therapeutic strategy for treating chronic itch. Show less

While essential trace minerals are known to influence DNA methylation (DNAm), molybdenum's (Mo) role in epigenetic regulation remains largely unexplored. This study examined associations between Mo status and DNAm of the brain-derived neurotrophic factor (BDNF) gene, a critical regulator of neurogenesis, in children aged 9-11 years, focusing on 107 CpG sites across BDNF and its antisense transcript (BDNF-AS).BDNF and BDNF-AS methylation was analyzed in blood samples from 72 children randomly selected from a cohort of 292 participants. Dietary Mo intake was estimated from food records, and creatinine-adjusted urinary Mo levels were quantified. Higher urinary molybdenum was significantly associated with decreased methylation at five BDNF 5'UTR sites (p<.05) and increased methylation of BDNF-AS (p =  .0001), consistent with enhanced BDNF transcriptional activity. African American children exhibited lower urinary Mo excretion than European American children, suggesting greater retention, and showed cortisol-associated increases in BDNF methylation not observed in European American children.These findings demonstrate associations between molybdenum status and DNA methylation patterns at the BDNF locus in children. While functional validation through BDNF protein measurement is needed, results suggest molybdenum may influence neurotrophin gene regulation through epigenetic mechanisms, highlighting the importance of trace mineral nutrition during neurodevelopment. Show less

Chronic pain is a highly prevalent and disabling condition with a well-documented female predominance in incidence, severity and persistence. These sex differences are driven by sexually dimorphic neuroimmune mechanisms rather than psychosocial factors alone. This systematic review was conducted to comprehensively synthesize human clinical and translational evidence on sex-specific neuroimmune and glial cell pathways underlying chronic pain. Scientific literature was systematically searched from database inception to December 2025 across multiple biomedical databases to identify relevant clinical and translational studies. Across pain conditions, convergent evidence demonstrated that chronic pain mechanisms diverge by sex at cellular and molecular levels. Male-predominant pathways were characterized by microglial activation, particularly P2X4 receptor-mediated signaling and brain-derived neurotrophic factor-dependent neuronal disinhibition, supported by neuroimaging, transcriptomic, and pharmacological data. In contrast, female-predominant mechanisms involved adaptive immune processes, including CD4 Show less

Chronic hepatitis B virus (HBV) infection is a major risk factor of hepatocellular carcinoma (HCC), and hepatocyte-derived host factors play important roles in HBV-associated tumor progression. Alpha-1B glycoprotein (A1BG) is a plasma glycoprotein reported to be dysregulated in multiple cancers. In this study, we investigated the functional role of A1BG in HBV-associated HCC progression. Both the HepG2 and HBV-transfected HepG2 cell lines were used to examine the biological effects of A1BG. A1BG expression was modulated using siRNA and a plasmid vector. A series of functional assays were conducted to assess cell proliferation, apoptosis, stemness, migration, and invasion. RNA microarray analysis and gene set enrichment analysis (GSEA) were performed to identify A1BG-regulated pathways. Functionally, A1BG overexpression suppressed cell proliferation, stemness, migration, invasion, and HBV products while promoting apoptosis in both HepG2 and HBV-transfected HepG2 cells. In contrast, opposite effects were shown in the event of A1BG knockdown. Moreover, A1BG expression was reduced in HBV-associated HCC tissues and correlated with advanced pathological stage and poor prognosis. RNA microarray analysis and GSEA revealed the activation of anti-HBV-related genes and suppression of FGFR1 signaling and the matrix metalloproteinase pathway in A1BG-overexpressing cells. This study provides evidence that A1BG may be a novel host factor associated with the in vitro suppression of HBV replication and HCC progression by modulating pathways related to enhanced antiviral effects, reduced proliferative capacity and stemness, and suppression of EMT. These findings suggest that A1BG is a potential therapeutic target in HBV-related HCC. Show less

Aging disrupts the neurovascular unit (NVU) and blood-brain barrier (BBB), elevates glial inflammatory tone, and compromises hippocampal memory. Environmental enrichment (EE)-a multimodal, lifestyle-based intervention-improves cognition, but its association with BBB/NVU and FNDC5/irisin-related signaling in aging remains incompletely understood. Aged male C57BL/6J mice (21 months old) were housed under EE or standard conditions for 11 weeks. Hippocampal-dependent spatial working memory was assessed using the radial eight-arm maze, and neuronal (NeuN), glial (Iba1, GFAP), and BBB/NVU markers (AQP4 endfoot polarity, occludin, ZO-1, PECAM-1, microvessel length/density) were quantified. FNDC5/irisin-related signaling was evaluated by measuring PGC-1α, FNDC5/irisin, IGF-1, BDNF, Show less

With the aim of identifying key proteins that play a role in the disorder tinnitus, interactions between proteins involved in thalamo-amygdala signaling under conditions of normal hearing (NH), acoustic stimulation (AS), and tinnitus (Tin) were studied. Three gene lists compiled from the GeneCards database using keywords were characterized by analyses of overlap, protein-protein interaction (PPI) networks, and by protein-enrichment analysis. Key proteins were selected on the basis of the degree and combined score value of the corresponding PPI network. In the NH process, BDNF, CASP3, and PVALB were identified as high-degree proteins (HDPs). In the AS process, BDNF, PVALB, and DLG4 are the top three HDPs; in the Tin process, these are BDNF, APP, and TNF. In the Tin process, key proteins appear that differ pre- and postsynaptically from those detectable in NH or AS. The glucocorticoid receptor NR3C1 and its interaction with FKBP5, a glucocorticoid receptor-induced co-chaperone, appear to be of particular importance for the emotional aspects of tinnitus. In tinnitus, the HDPs, together with their high-score interaction proteins, indicate processes of chronic neurodegeneration and of changes in transcription, intercellular communication, and in the survival and growth of neurons. Show less

Familial partial lipodystrophy type 3 (FPLD3) is a rare autosomal dominant disorder caused by mutations in peroxisome proliferator-activated receptor gamma(PPARG), which encodes the key adipogenic transcription factor peroxisome proliferator-activated receptor gamma(PPARγ). Clinical diagnosis is challenging due to phenotypic overlap with common metabolic syndromes. We identified a novel PPARG variant in a Chinese family and performed comprehensive functional characterization to elucidate its pathogenic mechanism. The proband, a 15-year-old boy presenting with atypical fat distribution, severe insulin resistance, hypertriglyceridemia, and pancreatitis, underwent clinical evaluation and whole-exome sequencing. The identified variant was confirmed by Sanger sequencing. Its functional impact was assessed through in silico modeling, luciferase reporter assays, protein stability analysis (cycloheximide chase), and evaluation of mitochondrial function (JC-1 staining) and adipocyte gene expression in cellular models. A heterozygous PPARG c.634C>T (p.Arg212Trp, R212W) variant was identified and segregated with the phenotype. Functional studies revealed that the R212W mutant exhibits a partial loss of transcriptional activity (~40% of wild-type) while retaining ligand sensitivity. Crucially, we demonstrated that the mutant protein has significantly reduced stability due to accelerated degradation. In adipocyte models, R212W expression led to impaired mitochondrial membrane potential, depleted cellular ATP levels, and downregulated expression of key metabolic genes (glucose transporter 4[GLUT4], adiponectin[ADIPOQ], fatty acid binding protein 4[FABP4], lipoprotein lipase[LPL], perilipin 1[PLIN1]). These functional deficits were partially rescued by treatment with the PPARγ agonist rosiglitazone. We report a novel pathogenic PPARG R212W variant associated with FPLD3. Our data extend beyond a simple loss-of-function model by establishing a multi-faceted pathogenic mechanism involving protein destabilization, mitochondrial dysfunction, and cellular bioenergetic failure. The partial rescue by rosiglitazone suggests a potential therapeutic avenue. This study underscores the importance of integrating clinical phenotyping with deep functional analysis to diagnose and understand rare monogenic lipodystrophies. Show less

Erectile dysfunction (ED) is one of the most prevalent and disabling complications of diabetes mellitus (DM), thought to arise from the interaction of metabolic, vascular, and neural injury. Recent evidence indicates that diabetic neuropathy, affecting both somatic and autonomic pathways, plays a central role in the development of ED and is strongly associated with increased disease burden. Early neurophysiological studies documented impaired penile sensory conduction and abnormalities of sacral reflex pathways in diabetic men with ED, while more recent investigations have confirmed the contribution of cardiovascular autonomic neuropathy and small-fibre loss. At the molecular level, oxidative stress, advanced glycation end-product signalling, impaired nitric oxide bioavailability, and reduced neurotrophic support, particularly involving brain-derived neurotrophic factor (BDNF), emerge as key mechanisms linking diabetes to neural and neurovascular dysfunction. Although phosphodiesterase type-5 inhibitors remain first-line therapy, reduced responsiveness in patients with significant neuropathy highlights the importance of recognising the role of neurogenic mechanisms. Overall, the available evidence supports the conceptualisation of diabetic ED as a neurovascular manifestation within the broader spectrum of diabetic neuropathy rather than as a purely vasculogenic disorder. This review integrates historical and contemporary literature addressing the epidemiology, neurophysiology, pathophysiology and therapeutic implications of ED in diabetes, with a specific focus on its neuropathic substrate. These findings support a paradigm shift toward an integrated neurovascular approach to diabetic ED, highlighting the importance of early neuropathy-oriented assessment and paving the way for future regenerative and neuroprotective therapeutic strategies. Show less

Among more than 300 candidate genes for obesity, A total of 231 healthy adults aged 19-64 years were recruited between March and May 2024. Anthropometric and clinical measurements, genotyping, dietary intake, and questionnaires on socioeconomic status, family history, and lifestyle behaviors were obtained. Associations between genotypes and obesity-related phenotypes were evaluated using ANOVA and ANCOVA, multivariable-adjusted models and multicollinearity analysis-based stepwise regression. In Koreans, MAFs for These findings support the relevance of Show less

Glaucoma is increasingly recognized as an ischemic neurodegenerative disorder that extends beyond elevated intraocular pressure (IOP) to involve complex vascular, metabolic, and inflammatory mechanisms. Retinal ganglion cells are particularly vulnerable to ischemia-reperfusion injury, oxidative stress, and chronic neuroinflammation, leading to progressive disconnection from central visual pathways. Current therapies primarily target IOP reduction but fail to address ischemia-driven neurodegeneration or to restore lost neuronal connectivity. Ischemia triggers excitotoxicity, oxidative stress, and a maladaptive inflammatory response involving activated microglia and astrocytes, perpetuating neuronal injury and suppressing intrinsic regenerative capacity. Thus, restoring neural plasticity and mitigating neuroinflammation represent key unmet therapeutic needs. Psychoplastogens are a class of compounds capable of rapidly enhancing structural and functional neuroplasticity and have recently emerged as promising multitarget agents. Compounds such as ketamine, psilocybin, N,N-dimethyltryptamine (DMT), and some newly synthesized non-hallucinogenic analogs act through convergent signaling pathways involving BDNF-TrkB-mTOR, promoting dendritic growth, synaptogenesis, and glial modulation. Beyond their neurotrophic effects, psychoplastogens seem to exert potent immunomodulatory actions. In this review we will explore the interplay between ischemia, neurodegeneration, neuroinflammation, and impaired plasticity in glaucoma, integrating mechanistic insights from cerebral ischemia. We discuss emerging preclinical evidence supporting psychoplastogens as neurorestorative and anti-inflammatory agents, propose their potential application in ocular ischemic neurodegeneration, and outline translational challenges for future studies. Show less

The origins of major depressive disorder (MDD) are complex, involving both environmental influences and a substantial genetic contribution. Genetic polymorphisms have been implicated in modulating susceptibility, disease course, and treatment response, yet findings are often modest, population-dependent, and sometimes inconsistent. This narrative review synthesizes current evidence on genetic variants associated with MDD, highlighting well-replicated results while distinguishing exploratory or emerging findings. Key systems reviewed include serotonergic ( Show less

A high-fat diet (HFD) induces oxidative stress and reduces hippocampal neurotrophic factors, contributing to cognitive impairment. Hydrogen sulfide (H₂S) is an endogenous gaseous signaling molecule with recognized neuroprotective and antioxidant properties. This study investigated the effects of sodium hydrosulfide (NaHS), an H₂S donor, on hippocampal brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and oxidative stress in rats fed an HFD. Forty-two adult male Wistar rats were assigned to control or HFD groups, with or without daily NaHS administration (3 or 5 mg/kg) for 11 weeks. HFD feeding significantly decreased hippocampal BDNF and IGF-1 protein levels and reduced the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSR). NaHS treatment, particularly at 5 mg/kg, restored neurotrophic protein levels and normalized antioxidant enzyme activities. These effects occurred without consistent changes in mRNA expression, suggesting post-transcriptional regulation. Collectively, these findings demonstrate that H₂S mitigates HFD-induced neurotrophic and oxidative deficits, supporting its potential as a therapeutic strategy for obesity-related hippocampal dysfunction. Show less