📋 Browse Articles

Luminal breast cancer (LBC) is the most common subtype of breast cancer affecting women worldwide. Although luminal breast cancer typically has a better prognosis, it mostly responds poorly to neoadjuvant chemotherapy. Non-coding RNAs, especially long non-coding RNAs and microRNAs are crucial in regulating biological processes that contribute to breast cancer development. MALAT1, a long non-coding RNA, is pivotal in the progression of breast cancer. Epithelial-mesenchymal transition (EMT) is critical for cell movement during embryonic development. Clarifying this role could pave various avenues for developing innovative strategies for combating this subtype of malignancy. The present study aimed to investigate the expression profiles and clinical relevance of MALAT1 level and EMT-related miRNAs (miR-17-5p, miR-20a-5p, miR-93-5p, miR-135b-5p, and miR-146a-5p) alongside EMT markers (E-cadherin, N-cadherin, vimentin, fibronectin, twist, SNAI1, Slug, ZEB1, and ZEB2) in LBC patients. Fresh tissues were collected from fifty patients and twenty noncancerous controls. Differential expression of the markers was evaluated using qRT-PCR assay. Spearman Rho test assessed the relationship between the expression levels. Linear regression test evaluated the correlation between the parameters and various clinico-pathological features. Our results revealed an overall upregulation of MALAT1 in breast cancer tissues although this increase did not reach statistical significance. Overexpression of miR-20a-5p, miR-135b, and ZEB2 was reported, whereas miR146a-5p, ZEB1 and Vimentin levels were suppressed. Correlation analysis demonstrated that miR-20a-5p was positively correlated with SNAI1, E-cadherin, N-cadherin and Slug also it was significantly associated with family history and tumor laterality. Our findings suggest that miR-20a-5p plays an oncogenic role in luminal breast cancer by promoting EMT, while MALAT1 may contribute to disease progression through indirect regulatory mechanisms. Finally, MALAT1 and miR-20a-5p might serve as potential therapeutic and prognostic targets in LBC. Show less

Olive pomace (OP), a by-product of olive oil production, is a sustainable resource rich in bioactive compounds with potential applications in cosmetics and pharmaceuticals. This study investigates the protective effects of olive pomace juice (OPJ) against H Show less

Nutrient competition between tumor and immune cells is a hallmark of the glioblastoma (GBM) microenvironment, yet the mechanisms underlying amino acid metabolic reprogramming and immune evasion remain incompletely understood. Here, we demonstrate that GBM cells outcompete NK cells for branched-chain amino acid (BCAA), leading to BCAA depletion, suppression of NK and CD8 Show less

Late-onset Alzheimer's disease is a devastating and complex neurodegenerative disorder with a multifactorial etiology. Over the past decade, advances in genetic research have identified novel risk genes, shedding light on the underlying pathogenic mechanisms of late-onset Alzheimer's disease. This review provides a comprehensive overview of several of these crucial genetic factors and their potential mechanisms in the pathogenesis of Alzheimer's disease. Genome-wide association studies, whole-genome sequencing, and multi-omics studies have played a crucial role in identifying key risk genes, particularly those involved in amyloid-β metabolism and clearance, such as CLU and APOE, which influence amyloid-β aggregation. Tau pathology, characterized by neurofibrillary tangles, is another hallmark of Alzheimer's disease, with genes such as BIN1 implicated in tau-mediated neurodegeneration. Additionally, immune regulatory genes, including CR1, MS4A6A, CD33, and TREM2, play crucial roles in microglial activation and neuroinflammation, thereby contributing to disease progression. Synaptic dysfunction is also a critical factor in Alzheimer's disease pathology, with genes such as IQCK, EPHA1, and CD2AP linked to synaptic function and plasticity, highlighting their potential impact on cognitive decline. Understanding these genetic risk factors provides valuable insights into the complex genetic landscape of Alzheimer's disease and its highly heterogeneous pathological mechanisms, including amyloid-β metabolism, tau pathology, immune response and neuroinflammation, and synaptic dysfunction. Future research should focus on elucidating the functional roles of these individual genes and their potential as therapeutic targets for altering the course of Alzheimer's disease. Show less

Illness perceptions have been associated with outcomes in patients with atrial fibrillation (AF). This study aimed to identify distinct illness perception profiles in patients with AF and examine their associations with psychological and physical responses. A total of 150 patients with AF were enrolled in this study. Illness perception profiles were identified using latent profile analysis (LPA). Model fit indices were evaluated to determine the optimal class solution. Logistic regression analyses were conducted to examine the associations between illness perception profiles and psychological and physical outcomes, including Generalized anxiety disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), 12-Item Short Form Health Survey (SF-12) and University of Toronto atrial fibrillation severity scale (AFSS). A two-class model was identified as optimal, comprising a "Reactive-Minimizing" profile (Class 1, 49%) and a "Symptom-Helplessness" profile (Class 2, 51%). Univariate logistic analysis revealed significant differences between classes in age, AF type, work status, PHQ-9, AFSS-symptoms, and AFSS-burden. In the multivariable logistic regression adjusted for age and sex (logistic outcome: Class 2 vs. Class 1), higher AFSS-burden scores were independently associated with the "Symptom-Helplessness" profile (OR = 1.26, 95% CI: 1.09-1.45, p = 0.001). Conversely, higher PHQ-9 scores were associated with the "Reactive-Minimizing" profile (OR for Symptom-Helplessness = 0.92, 95% CI: 0.86-0.99, p = 0.018). Person-centered illness perception profiling revealed two distinct cognitive-emotional patterns in patients with AF that were associated with depressive symptoms and symptom burden, highlighting their potential value for individualized psychological and clinical management. Show less

Depression imposes significant social, economic, and health burdens worldwide. Although phlorotannin-rich extract from Ecklonia cava (PS) and its active compound dieckol (DK) exhibit various biological activities, their antidepressant- and anxiolytic-like effects and underlying mechanisms remain unclear. This study investigated the antidepressant- and anxiolytic-like potential of PS and DK in a corticosterone (CORT)-induced mouse model of depression and anxiety, focusing on glucocorticoid receptor (GR) signaling. CORT-treated mice were orally administered PS or DK, and behavioral tests were performed to assess depressive- and anxiety-like behaviors. PS composition was analyzed using LC-MS/MS. Molecular docking predicted the binding of PS components to GR. GR nuclear translocation, target gene expression, and downstream signaling were examined using behavioral, molecular, and computational approaches. PS alleviated CORT-induced depressive- and anxiety-like behaviors, accompanied by reduced GR nuclear translocation, suppression of Mkp-1, and restoration of ERK-CREB-BDNF signaling. Molecular docking analysis predicted strong binding of DK to the GR ligand-binding domain. Consistently, DK reduced GR nuclear translocation and GRE binding, downregulated GR target genes (Mkp-1, Sgk-1, Fkbp5, and Bdnf), and restored ERK-CREB-BDNF signaling. In vivo, DK also improved CORT-induced behavioral deficits and normalized HPA axis activity and neurotransmitter levels. Collectively, our results suggest that DK, a major bioactive phlorotannin from E. cava, exerts antidepressant- and anxiolytic-like effects in association with modulation antagonism of GR signaling, highlighting its therapeutic potential as a natural GR-modulating agent for stress-related mood disorders. Show less

Psychological well-being among university students is often examined using variable-centered approaches that assume population homogeneity. Using Ryff's eudaimonic model and a person-centered analytic framework, this study examined latent profiles of psychological well-being among Ghanaian undergraduates, offering insight into how the Western-derived model functions in a non-Western cultural context. A cross-sectional design was employed to sample 574 regular undergraduate students from a public university in Ghana. Students completed the 18-item Ryff's Psychological Well-Being Scale. Latent profile analysis (LPA) followed by Chi-square tests were performed using JAMOVI statistical software. Four distinct profiles emerged: fully flourishing students (38.7%), harmonious life seekers (45.1%), purposeful self-actualizers (7.5%), and aspiring actualizers (8.7%). The profiles differed primarily in levels of autonomy, personal growth, and environmental mastery. Well-being profile membership was not associated with gender but varied significantly by age, although the effect size was small. The study findings suggest meaningful heterogeneity in eudaimonic well-being among Ghanaian undergraduates and highlight the importance of culturally sensitive, profile-based mental health interventions beyond demographic assumptions. Show less

Current evidence is unclear due to methodological limitations. We bridge critical knowledge gaps by quantifying the longitudinal changes in movement behaviours and their correlates from early childhood through adolescence. Longitudinal observational cohort study. General healthy child and adolescent sample in Singapore. Growing Up in Singapore Towards healthy Outcomes study participants. We used wrist-worn accelerometry and proxy-reported data to examine movement behaviours (sleep, inactivity, light physical activity (PA; LPA) and moderate-to-vigorous PA (MVPA) and screen-viewing) at ages 5.5, 8, 10 and 12 years and the sociodemographic and maternal lifestyle-related correlates using linear regression models with generalised estimating equations. Among 837 children, sleep, LPA and MVPA declined by 3% (from 9.1 to 8.8 hours/day), 24% (from 5.8 to 4.4 hours/day) and 44% (from 71.3 to 40.1 min/day), respectively, while inactivity and screen viewing increased by 26% (from 8.0 to 10.1 hours/day) and 155% (from 1.8 to 4.6 hours/day), respectively, from ages 5.5 to 12 years. The greatest annual increase in inactivity (0.6 hour/annum) and screen-viewing (0.8 hour/annum) and decrease in LPA (0.3 hour/annum) and MVPA (10.4 min/annum) occurred from ages 8 to 10 years. Girls of Malay ethnicity and lower socioeconomic status, and whose mothers had less favourable movement behaviours, had significantly less sleep, higher inactivity and screen-viewing and/or lower PA. Maternal PA levels and/or sitting time were associated with children's sleep, inactivity and MVPA up to age 8 years, while maternal sitting and screen-viewing behaviours were associated with children's screen-viewing at all ages. Using contemporaneous datasets relevant to the present day, we confirmed that children become less physically active and have longer screen-viewing as they transition into adolescence and highlighted characteristics to be prioritised in future interventions. Show less

Exercise-induced inflammation has been shown to influence iron metabolism. Conversely, ischemic preconditioning (IPC) has been proposed as a strategy to modulate post-exercise response, especially inflammation and neurotrophic factor secretion. In this study we analyzed the effects of a 14-days IPC intervention on the post-exercises changes of the selected Iron metabolism, inflammation and neurotrophic markers in the population of non-training healthy young man. Forty healthy, untrained young men voluntarily participated in this study and were randomly assigned to two groups: an IPC group (n = 20), which underwent a 14-day IPC intervention, and a placebo (SHAM) group (n = 20). Five participants from the IPC group and seven from the SHAM group did not complete the protocol and were excluded from the analyzes. Venous blood samples were collected at rest, immediately after and 2 h after the Wingate test. Selected inflammatory and neurotrophic markers were analyzed, including IL-6, IL-10, IL-15, LIF, BDNF, IGF-1, NGF, sAPPα, FSTL-1, and GDF-15. Additionally, serum levels of iron (Fe), hepcidin (Hpc), ferritin (Fer), erythroferrone (ERFE), and erythropoietin (EPO) were assessed. IPC increased resting ferritin (~ + 9%, p < 0.05), hepcidin (~ + 12%, p < 0.05), and erythroferrone (~ + 10%, p < 0.05) concentrations. The intervention also enhanced post-exercise IGF-1 (+ 8%, p = 0.03) and sAPPα (+ 10%, p = 0.04) release and reshaped cytokine profiles, with greater early elevations of GDF-15 and IL-15 (p < 0.05) and faster normalization of FSTL-1 within 2 h (p < 0.05). IPC further affected neurotrophic signaling, showing lower 2-h post-exercise BDNF levels (p < 0.05) and distinct IGF-1 kinetics (p < 0.01). Anaerobic performance remained unchanged (p > 0.05). Ischemic preconditioning induces coordinated alterations in iron metabolism and modulates inflammatory and neurotrophic responses to anaerobic exercise, without affecting physical performance in untrained individuals. Show less

Symptomatic neuromas result from disorganized nerve growth at the site of amputation, causing pain that affects recovery and quality of life. In patients with diabetes mellitus (DM), nerve regeneration is impaired, compounded by comorbidities such as obesity, hypertension, and hyperlipidemia. Surgical approaches including targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) have shown promise for managing symptomatic neuroma, but their effectiveness in diabetic patients is uncertain due to unique challenges in nerve regeneration. This narrative review explores the protective effects of DM on symptomatic neuroma formation and to evaluate the implications for surgical intervention. A systematic search of PubMed was conducted, and relevant studies discussing symptomatic neuroma formation in amputees were included. Symptomatic neuromas were reported in 9.5-50% of amputees involving 9.5% of upper extremity, and 3.8% of lower extremity amputees. Younger age and proximal amputations were identified as significant risk factors. While it is suggested that Interleukin (IL)-10 and brain-derived neurotropic factor (BDNF) levels are involved in protecting against symptomatic neuroma formation, IL-1β and IL-6 promote neuroma formation. Although evidence is mixed, some evidence suggests that DM and diabetic peripheral neuropathy decrease symptomatic neuroma formation by impairing axonal regeneration, altering the extracellular matrix and modulating inflammatory responses. Although surgical approaches such as TMR and RPNI have shown potential in reducing neuroma-related pain, further studies are needed to ensure that this benefit extends to diabetic patients whose disease puts them at increased risk of postoperative complications. Additional studies are required to confirm these findings and optimize surgical strategies for high-risk patient populations. Show less

Testosterone production by testicular Leydig cells (steroidogenesis) is vital to male fertility and overall male health. Information about how nutrition influences Leydig cell steroidogenesis is lacking. Branched chain amino acids (BCAAs - leucine, isoleucine, and valine) are essential amino acids and important regulators of protein synthesis and energy production. Circulating and tissue BCAA levels are tightly regulated by the enzyme branched chain a-keto acid dehydrogenase kinase (BCKDK), which inhibits their catabolism. This work explored how BCAAs, and especially leucine, modulate male fertility and testosterone production. In a mutant mouse model of Bckdk, breeding analysis showed reduced male fertility and circulating testosterone. Further, morphological evaluation demonstrated testicular and epididymal abnormalities consistent with abnormal testicular androgen signaling. Fertility was partially rescued by feeding a high protein diet while circulating testosterone was not. In wild type testes, Leydig cells were the primary cell type to express BCKDK. Leveraging a primary interstitial cell culture, cell survival and apoptosis analyses demonstrated Leydig cells are highly sensitive to leucine deprivation and this sensitivity is enhanced under steroidogenesis stimulating conditions. Lastly, using the same primary cell culture system, testosterone production was shown to be lost under leucine deprivation. In total, this work demonstrates Leydig cells are uniquely sensitive to BCAA status under steroidogenesis stimulation and that regulated BCAA catabolism may be important for optimal male fertility. Show less

N-Acetylcysteine (NAC), a thiol-containing antioxidant, has demonstrated neuroprotective potential in various neurological disorders. Recently, cold atmospheric plasma (CAP) technology has emerged as a promising approach for modifying the physicochemical properties of biomolecules. This study investigated the neuroprotective effects of plasma-activated N-acetylcysteine (PAN) in a rat model of intracerebroventricular streptozotocin (icv-STZ)-induced cognitive impairment, with particular emphasis on redox homeostasis and cholinergic function. The physicochemical properties of PAN were characterized using FTIR, LC-MS/MS, and DPPH assay. Male rats received a single icv-STZ injection (3 mg/kg) on day 0, followed by oral administration of NAC or PAN (50 mg/kg) every other day for three weeks. Cognitive performance and anxiety-like behaviors were assessed using the shuttle box, novel object recognition, and elevated plus maze tests. Subsequently, oxidative stress indices (TAC, GSH, SOD, CAT, MDA, NO), cholinergic markers (AChE activity, ACh levels), and the expression of AChE, α7 nAChR, Nrf2, Keap1 and BDNF genes were quantified in the hippocampus and cerebral cortex. FTIR and LC-MS/MS analyses revealed plasma-induced chemical modifications in NAC, resulting in the generation of novel compounds. The DPPH assay further demonstrated superior radical scavenging activity of PAN compared with NAC. Behaviorally, PAN administration significantly alleviated STZ-induced cognitive deficits and anxiety-like behaviors. Biochemically, PAN normalized TAC, GSH, MDA, NO, and ACh levels, increased CAT and SOD activities, and reduced AChE activity. At the transcriptional level, PAN upregulated α7 nAChR, Nrf2 and BDNF expression while downregulating AChE and Keap1. Collectively, these findings suggest that PAN mitigates behavioral impairments in the icv-STZ rat model of Alzheimer's disease, potentially through attenuation of oxidative stress and restoration of cholinergic neurotransmission. Show less

Hypertrophic cardiomyopathy (HCM) is a complex myocardial disorder with heterogeneous clinical presentations and structural manifestations. This study aimed to assess the distribution, clinical characteristics, and diagnostic approaches in a regional cohort of patients with HCM. Patients diagnosed with HCM at a tertiary cardiomyopathy clinic between October 2021 and November 2024 were retrospectively analyzed. Patients were classified into obstructive, latent obstructive, non-obstructive, or apical phenotypes based on clinical and imaging findings. Comprehensive demographic, clinical, and imaging data were collected for detailed analysis, providing valuable insights into the phenotypic diversity of HCM. The cohort included 701 patients with a median age of 53 years of whom 68% were male. The phenotypic distribution comprised 9.3% apical, 38.1% non-obstructive, 32.5% resting obstructive, and 20.1% latent obstructive HCM. Implantable cardioverter-defibrillator implantation was more common in obstructive phenotypes, particularly in the latent obstructive group. Although late gadolinium enhancement (LGE) was more frequently observed in apical HCM, post-hoc analysis showed no significant difference in prevalence across subgroups. In contrast, LGE extent was significantly greater in the apical group. Genetic testing, performed in 32% of patients, revealed a 44% positivity rate, with MYBPC3 and MYH7 being the most commonly detected mutations. The overall mortality rate was 2.8%, with heart failure identified as the leading cause of death. In this large regional cohort of HCM patients, obstructive and non-obstructive phenotypes were predominant, with a notable burden of genetic mutations and a low overall mortality rate primarily driven by heart failure. These findings emphasize the clinical heterogeneity of HCM and highlight the importance of comprehensive diagnostic evaluation. Show less

This study was conducted to assess the clinical significance of programmed cell death-ligand 1 (PD-L1)-positive circulating tumor cells (CTCs) as predictive biomarkers for the efficacy of PD-(L)1 inhibitor-based treatment in advanced hepatocellular carcinoma (HCC). We enrolled 59 patients with unresectable HCC who received immunotherapy-based treatment and analyzed CTCs, PD-L1 CTCs were detected in 86.4% (51/59) of patients, with a PD-L1-positive rate of 83.7% (41/49). Compared with the "PD-L1 PD-L1 Show less

Fetal growth restriction (FGR) remains a significant problem in obstetrics and is a key risk factor for perinatal brain injury. The fetal neuronal vesicles (FNVs) isolated from maternal blood represent an innovative approach-a "fetal brain liquid biopsy"-enabling early diagnostics of neuronal dysfunction in FGR. Western blotting was used to evaluate the protein pattern expression of FNVs isolated from the blood of pregnant women with FGR and uncomplicated pregnancy. Significant changes in the neurotrophic proteins levels (pro-BDNF, pro-NGF) and presynaptic neurotransmission proteins (SYN1, SYP, SYNPO) were identified. New data were obtained on changes in the expression of proteins of sumoylation (SUMO2/3/4) and neddylation (NAE1, UBC12), which differs in early-onset and late-onset FGR. Moreover, increased SUMO2/3/4 levels can be considered as an endogenous neuroprotective response to cerebral hemodynamic reaction in fetuses with late-onset growth restriction. An association has been established between changes in the expression of the studied proteins and intraventricular hemorrhage (IVH) in newborns with late-onset growth restriction. Show less

Tuberculous pyomyositis is a rare and often under-recognized extrapulmonary manifestation of tuberculosis, presenting with non-specific symptoms such as fever and abscess, that may delay diagnosis. We report a unique case of disseminated tuberculous pyomyositis in a 56-year-old male with underlying chronic inflammatory arthritis. The diagnosis was confirmed using CBNAAT, line probe assay (LPA), and histopathology. Currently MRI is the standard imaging modality in use for imaging pyomyositis. Show less

The incidence of multiple sclerosis (MS) has increased in recent years. Its pathogenesis involves the interaction between various elements, with interleukin 27 (IL-27) playing a key role in autoimmunity. The presence of the IL-27 receptor on astrocytes emphasizes its involvement in the disease's progression. The study aims to investigate possible associations between IL27 rs181206, serum level of IL27, and the development of MS. The study comprised 70 MS patients and 70 seemingly healthy controls. They were genotyped for IL27 rs181206 using the Taqman allelic discrimination approach, and their serum IL27 levels were estimated using ELISA. The frequency of TT genotype, T allele, and IL27 serum level were significantly higher among MS patients compared to controls. There was no significant difference between IL27 serum levels among different genotypes in both MS patients and controls; however, individuals with TT genotype showed higher levels of IL27 than those with CC genotype. TT genotype and T allele can increase the risk of developing MS. On the other hand, carrying the C allele may be associated with a lower risk of MS development. Understanding IL27 genetics and epistatic interactions can help clarify IL27's role in MS pathogenesis and utilize it as a therapeutic target. Show less

Training adaptation involves muscular-metabolic remodeling and personality-linked traits such as motivation, self-regulation, and resilience. This narrative review examines how training load oscillation (TLO)-the deliberate variation in exercise intensity, volume, and substrate availability-may function as a systemic epigenetic stimulus capable of shaping both physiological and psychological adaptation. Fluctuating energetic states reconfigure key energy-sensing pathways (AMPK, mTOR, CaMKII, and SIRT1), thereby potentially influencing DNA methylation, histone acetylation, and microRNA programs linked to PGC-1α and BDNF. This review synthesizes converging evidence suggesting links between these molecular responses and behavioral consistency, cognitive control, and stress tolerance. Building on this literature, a systems model of molecular-behavioral coupling is proposed, in which TLO is hypothesized to entrain phase-shifted AMPK/SIRT1 and mTOR windows, alongside CaMKII intensity pulses and a delayed BDNF crest. The model generates testable predictions-such as amplitude-dependent PGC-1α demethylation, BDNF promoter acetylation, and NR3C1 recalibration under recovery-weighted cycles-and highlights practical implications for timing nutritional, cognitive, and recovery inputs to molecular windows. Understanding TLO as an entrainment signal may help integrate physiology and psychology within a coherent, durable performance strategy. This framework is conceptual in scope and intended to generate testable hypotheses rather than assert definitive mechanisms, providing a structured basis for future empirical investigations integrating molecular, physiological, and behavioral outcomes. Show less

This study aimed to evaluate serum brain-derived neurotrophic factor levels, stress, and quality of life in leprosy patients, and to explore their interrelations. A cross-sectional study was conducted from September 2024 to May 2025 at 3 hospitals in Medan, Indonesia, involving 45 leprosy patients aged ≥ 18 years who met inclusion criteria. Serum brain-derived neurotrophic factor levels were measured using ELISA, stress was assessed using the Perceived Stress Scale-10, and quality of life was evaluated through the WHOQOL-BREF questionnaire. Descriptive statistics, Shapiro-Wilk normality test, and Spearman's rank correlation were used for analysis. The mean serum brain-derived neurotrophic factor level was 7.38±3.37 ng/mL. Patients with multibacillary leprosy without reaction had higher brain-derived neurotrophic factor levels than those with type 1 or type 2 reactions. Stress levels were mild in 42.22% and severe in 28.89% of patients. Quality of life scores varied widely. A strong negative correlation was found between brain-derived neurotrophic factor and stress (r=-0.953, p< 0.0001), and a strong positive correlation between brain-derived neurotrophic factor and quality of life (r=0.962, p< 0.0001). These findings suggest that serum brain-derived neurotrophic factor levels are associated with psychological well-being in leprosy patients and may serve as a potential biomarker for mental health monitoring in this population. Show less

Brain derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) play crucial roles in neuronal development, synaptic transmission, and neuroplasticity. Deficits in BDNF/TrkB signalling and trafficking have been identified in several neurodegenerative diseases, including Alzheimer's disease (AD). Individuals with Down syndrome (DS) are at an increased risk of developing AD compared to the general population. Basal forebrain neurons (BFNs) are among the first to degenerate in AD and DS, but the mechanisms underlying their vulnerability remain unclear. Using BFNs derived from the Dp1Tyb mouse model of DS, we investigated neurotrophic signalling and trafficking deficits in AD-DS. We found enlarged early endosomes and elevated levels of active Rab5, a GTPase critical for early endosome formation, in Dp1Tyb BFNs. These abnormalities were associated with impaired transport of internalised TrkB from axon terminals to the soma. Using microfluidic devices, we demonstrated that axonal BDNF stimulation enhanced signalling endosome dynamics in wild-type but not Dp1Tyb BFNs, which is likely due to impaired axonal ERK1/2 signalling. Our findings establish a link between Rab5 hyperactivation, endosomal dysfunction, and impaired ERK1/2 signalling, highlighting the interplay between trafficking and neurotrophic signalling, and underscore the importance of targeting endolysosomal and signalling pathways to mitigate neuronal dysfunction in AD-DS. Show less

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., Show less

Novel therapeutic approaches, such as exosome therapy, have garnered considerable attention for the treatment of central nervous system (CNS)-related disorders. This study aimed to investigate the effect of Neural stem cell-derived exosomes(Exo-NSC) on improving behavioral, molecular, and electrophysiological symptoms. Rats were divided into: control, lesioned groups (Alz, Alz + saline), treatments (Alz + NSC, Alz + Exo-NSC). the nucleus basalis of meynert (NBM) was lesioned using electrical lesion. One week after lesion, saline, NSC, and Exo-NSC were injected into the NBM. Twenty-eight days post-injection, behavioral tests (passive avoidance memory and locomotor activity) and EEG recordings were conducted. Subsequently, hippocampal levels of brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) were measured. NBM lesioning significantly reduced the step-through latency (STL), decreased alpha and gamma wave frequencies, increased theta and delta wave frequencies, and reduced Ach and BDNF levels compared to the control group. The NSC injection resulted in decreased delta wave frequency, increased gamma wave frequency, and elevated BDNF levels. Meanwhile, Exo-NSC injection significantly increased STL, beta and gamma wave frequencies, and levels of ACh and BDNF compared to lesioned groups. Overall, the findings indicate that Exo-NSC injection may be more effective than NSCs in improving passive avoidance memory. This benefit may stem from elevated hippocampal ACh and BDNF levels in the hippocampus. Show less

Alzheimer's disease (AD) pathology disrupts functional brain connectivity long before symptoms emerge. African Americans face elevated AD risk, yet underlying mechanisms remain unclear. Genetic risk differs by ancestry: APOE-ε4 strongly predicts late-onset AD in European ancestry, whereas ABCA7 rs115550680 confers substantial risk in African ancestry. Yet, how these variants influence neural function in African Americans is unclear. The medial temporal lobe (MTL) is an early target of AD pathology and resting-state functional Magnetic Resonance Imaging (rs-fMRI) measures of dynamic network connectivity (hereafter "flexibility"), the brain's capacity to dynamically reconfigure connectivity, provide a sensitive metric of network adaptability, potentially preceding structural decline. However, comparative influence of APOE-ε4 and ABCA7 rs115550680 on MTL flexibility and subregional volumes in this population is unknown. 146 older African Americans (Mean Show less

Neuroprotection represents a promising approach for mitigating retinal degeneration. Cord blood serum (CBS), rich in trophic factors such as the brain-derived neurotrophic factor (BDNF), has shown therapeutic potential for ocular surface diseases; however, its role in retinal neuroprotection remains underexplored. This study evaluates the protective effects of CBS on retinal pigment epithelium (ARPE-19) and photoreceptor-like (661W) cells exposed to oxidative stress. Cells were cultured in media supplemented with fetal bovine serum (FBS) or CBS with either high (CBS-H) or low (CBS-L) BDNF content. Oxidative stress was induced using hydrogen peroxide (H Show less

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are debilitating disorders with overlapping symptoms such as chronic pain and fatigue. Dysregulation of the endogenous opioid system, particularly µ-opioid receptor function, may contribute to their pathophysiology. This study examined whether epigenetic modifications, specifically µ-opioid receptor 1 gene ( Show less

Amyloid-β (Aβ) PET imaging is a core biomarker and is considered sufficient for the biological diagnosis of Alzheimer's disease (AD). However, it is typically reduced to a binary Aβ™/Aβ+ classification. In this study, we aimed to identify subgroups along the continuum of Aβ accumulation including subgroups within Aβ- and Aβ+. We used a total of 3,110 of Aβ PET scans from Alzheimer's Disease Neuroimaging Initiative (ADNI) and Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) datasets to develop Show less