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Although increased maternal androgens, such as those in polycystic ovary syndrome (PCOS), are associated with a higher incidence of autism spectrum disorder (ASD) in offspring, a causal link has yet to be established. We assessed whether perinatal hyperandrogenization in a murine model recapitulates core ASD traits and compared this model to the maternal immune activation (MIA) model of ASD. Both models produced ASD-like phenotypes, yet they exhibited distinct behavioral subtypes and neurodevelopmental trajectories. Hyperandrogenized offspring showed greater reductions in social communication (neonatal USVs, d = 0.633-0.773; juvenile USVs, d = 1.103-1.216; social preference, d = 0.715), whereas only MIA offspring showed increased repetitive behaviors (d = 0.599). Ex vivo magnetic resonance imaging revealed volume increases in specific cortical regions in both models, with MIA additionally showing absolute cingulate cortex enlargement, and hyperandrogenized mice displaying focal increases in sexually dimorphic regions, despite a 36% reduction in overall brain volume (FDR 10%). Placentas from both groups showed reduced LIX (CXCL5), but distinct immune shifts also emerged: MIA placentas exhibited elevated IL-4 and IL-1β, whereas hyperandrogenized placentas showed increased TNFα. In neonatal brains, both conditions were associated with reduced IL-2, with MIA additionally decreasing IL-17A and IL-12p70, suggesting suppression of Th1/Th17-type cytokine signaling that normally supports proinflammatory and immune-neural interactions. DRD2 and BDNF protein were upregulated in hyperandrogenized fetal brains but downregulated with MIA. These results suggest that hyperandrogenization and MIA act through distinct mechanisms, producing subtle neurodevelopmental and behavioral differences consistent with human ASD subtypes. 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

Social context modulates stress physiology and resilience, yet preclinical rat paradigms vary widely in stressor type, timing of social exposure, contact modality, and endpoint definitions. We synthesized rat studies to quantify directional and, where feasible, standardized effect-size evidence for social buffering and to outline translational implications. PubMed, Scopus, and Web of Science were searched (2008-2025) for in vivo rat studies comparing conspecific (pair/group housing or conspecific presence) versus solitary conditions across validated stress and PTSD-like paradigms (e.g., fear conditioning/extinction, CUS/CMS, social defeat, predator threat). Data extraction and reporting followed PRISMA 2020 and SYRCLE guidance. Synthesis followed a two-tier approach: (i) all eligible contrasts were direction-coded as beneficial, neutral/mixed, or detrimental under conspecific conditions based strictly on reported statistical contrasts; and (ii) for domains with sufficient coded contrasts, the proportion of beneficial comparisons was estimated with exact binomial tests and 95% confidence intervals. Standardized mean-difference meta-analysis (Hedges' g; random-effects REML) was conducted only for predefined outcomes with adequate numerical reporting. Forty studies met inclusion criteria, yielding 89 extracted comparisons. Overall, 69/89 comparisons (≈78%) favored conspecific conditions. Domain-level directional syntheses supported predominance of beneficial outcomes for hormonal (0.72; 95% CI 0.50-1.00; p = 0.048) and neurotrophic/plasticity markers (0.89; 95% CI 0.57-1.00; p = 0.020), whereas inflammatory/oxidative outcomes were more variable (0.71; 95% CI 0.39-0.94; p = 0.227). For predefined behavioral endpoints with sufficient data, effect-size pooling showed a large reduction in conditioned fear (Hedges' g = -1.22 [-1.53; -0.91], p < 0.0001). Social buffering is robust at behavioral and neuroendocrine levels and often aligns with neurotrophic/plasticity markers, while peripheral immune/redox readouts are more context-dependent. Show less

ObjectiveTo evaluate the effects of a combined psychological and functional exercise intervention on emotion, quality of life, and brain-derived neurotrophic factor (BDNF) levels in patients with Parkinson's disease (PD).MethodsIn this randomized controlled trial, 172 patients with PD were randomly assigned into 2 groups with 86 patients in each group. The control group received routine care, while the intervention group received a 12-week intervention combining psychological support with functional exercise in addition to routine care. Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Parkinson's Disease Questionnaire-39 (PDQ-39), Barthel Index, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and serum BDNF levels were assessed before and after the intervention. Adherence rates were also determined for each group. Spearman correlation analysis was used to examine associations between changes in BDNF (ΔBDNF) and changes in HAMA (ΔHAMA) and HAMD (ΔHAMD) scores.ResultsAt the end of the 12-week clinical trial, the intervention group demonstrated significantly lower HAMA, HAMD, PDQ-39, and MDS-UPDRS scores ( Show less

Recent studies have indicated that stem cells could provide therapeutic benefits in several neurological conditions, including Alzheimer's disease (AD). Adipose-derived stem cells (ADSCs) offer many advantages in that they are readily available from individual hosts, are robust, and secrete many factors that promote neuronal growth and homeostasis. We transfected ADSCs with a viral construct for brain-derived neurotrophic factor (BDNF) and examined the effects of transplanting these cells into the hippocampus of 7-mo-old APPswe/PS1dE9 mice. After 6 mo, the hippocampus was examined for stem-cell survival, effects on BDNF and neprilysin-2 (NEP-2) levels, dendritic morphology using microtubule associated protein 2 (MAP2) immunohistochemistry, and amyloid plaque load. We found that transplanted BDNF-ADSCs had survived after 6 mo. BDNF and NEP-2 levels were higher than sham controls, and dendritic architecture was improved. In addition, amyloid plaque numbers were reduced. BDNF-ADSCs appear to confer benefits by simultaneously enhancing amyloid clearance and promoting neuronal structural repair. This multifaceted approach highlights the potential of engineering stem cells to target multiple pathophysiological hallmarks of AD, positioning BDNF-ADSCs as a powerful and synergistic cell-gene therapy strategy for this devastating disorder. Show less

Ischemic stroke is one of the leading global causes of disability and death. Despite advances in modern medical technology that improve acute treatment and rehabilitation measures, post-stroke anxiety and depression (PSD) do not receive sufficient attention. To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice. This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024. Based on assessments using the Hamilton Rating Scale for Anxiety (HAMA) and Hamilton Rating Scale for Depression (HAMD) at 2 weeks (± 3 days) post-stroke, patients were classified into the PSD group (HAMA ≥ 7 and/or HAMD ≥ 7) and the non-PSD group (HAMA < 7 and HAMD < 7). Observation indicators included psychological assessment, demographic and clinical characteristics, stroke-related clinical indicators, neuroimaging assessments, and laboratory biomarkers. Multivariate logistic regression analysis was used to identify independent risk factors for PSD, and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers. Of the 112 patients, 46 (41.1%) were diagnosed with PSD. Multivariate analysis identified five independent risk factors: Female gender [Odds ratio (OR) = 2.32, 95% confidence interval (CI): 1.56-3.45], history of mental disorders prior to stroke (OR = 3.17, 95%CI: 1.89-5.32), infarct location in the frontal lobe or limbic system (OR = 2.86, 95%CI: 1.73-4.71), stroke severity with National Institutes of Health Stroke Scale ≥ 8 at admission (OR = 2.54, 95%CI: 1.62-3.99), and low social support (Social Support Rating Scale < 35, OR = 2.18, 95%CI: 1.42-3.36). Subgroup analysis showed that depression patients more commonly had left hemisphere lesions (68.4% PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry, neuroinflammatory responses, and dysfunction of the hypothalamic-pituitary-adrenal axis. Show less

Neurodegenerative diseases such as Huntington's Disease (HD) have a significant impact on healthcare accessibility and costs. A fatal genetic condition, characterized by the progressive loss of striatal neurons, HD is hindered by the lack of endogenous repair in the adult brain. Recent efforts toward protecting neural circuits through neurotrophic support using brain-derived neurotrophic factor (BDNF) have been suboptimal due to the protein's short half-life and limited diffusion. Addressing this, adeno-associated viral vectors (AAV) can be employed as a delivery tool to spatially transduce cells, enabling the localised production of BDNF with consequential neuron protection and/or plasticity, yet present their own constraints. To overcome these known challenges of AAV gene delivery, an injectable, physiologically stable hydrogel-mimic of the brain's extracellular matrix was fabricated to encapsulate the AAVs. This smart system both shielded and constrained the AAV; optimising transfection and therefore elevated and sustained BDNF presentation at the target site. Here, we achieved high neuroprotection using AAVDJ-BDNF delivered through a hydrogel formed via self-assembling peptide nanoscaffolds. These findings support the notion that the spatiotemporal release of BDNF to striatal neurons, facilitated by engineered biomaterial delivery systems, demonstrates tremendous promise by enhancing the efficacy of gene therapy targeted at slowing neurodegenerative disease progression. Show less

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration and increasingly associated with gut microbiota alterations. Roseburia intestinalis (R. intestinalis) is consistently reduced in PD; however, its functional contribution remains unknown. We performed two complementary mouse experiments using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model. In the primary intervention experiment, mice received live or heat-killed R. intestinalis, followed by behavioral assessments and multi-layer analyses, including immunofluorescence, western blotting, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, 16S rRNA sequencing, metabolomics, and transcriptomics. In a separate mechanistic experiment, subdiaphragmatic vagotomy was introduced to interrogate vagus-dependent gut-brain communication, with key behavioral and inflammatory endpoints assessed. Live R. intestinalis improved rotarod, pole, and grip strength performance and preserved tyrosine hydroxylase-positive neurons in the substantia nigra; however, these effects were not observed in the heat-killed group. Live R. intestinalis treatment also reduced glial reactivity, restored brain-derived neurotrophic factor expression, and maintained blood-brain barrier integrity. Systemically, R. intestinalis lowered serum lipopolysaccharide, tumor necrosis factor-α, and interleukin-6 levels; preserved colonic structure; and restored mucin-secreting goblet cell function. MPTP-induced dysbiosis was partially corrected. Metabolomic profiling revealed restoration of several acyl-carnitines and higher acetic acid levels. Transcriptomic analysis showed increased immediate early genes after MPTP, and the elevated c-Fos in the substantia nigra was partially normalized by R. intestinalis. Importantly, vagotomy abolished the central neuroprotective and anti-inflammatory effects but did not affect peripheral cytokine suppression, indicating both vagus-dependent and vagus-independent pathways. R. intestinalis supplementation alleviated motor impairments, reduced neuroinflammation, preserved dopaminergic neurons, and improved intestinal and metabolic alterations in mice with an MPTP-induced PD model. Its protective actions may involve both central and peripheral mechanisms, potentially including gut-brain communication pathways. R. intestinalis may be a promising candidate for microbiota-based strategies against PD. Show less

Previous Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD), whereas their associations with mild cognitive impairment (MCI) remain unclear. To evaluate the associations between 100 representative AD-associated SNPs and susceptibility to MCI in the Chinese population. We recruited 200 MCI patients and 200 cognitively-healthy controls from the community, matched for age and sex. Associations between SNPs and MCI risk were estimated using lasso regression, adjusted for APOE status, using different genetic models. Fifteen SNPs in nine genes (including CLU, SORL1, PICALM, BDNF, NOS3, MTHFR, TOMM40, BIN1, and PVRL2) were associated with MCI in single-SNP analysis. In the multi-SNP association test, rs1801133 and rs9331888 of CLU were consistently associated with MCI risk in the dominant model. TOMM40 rs2075650 (G) was associated with MCI risk in the dominant model by age and education (OR = 2.41, 95%CI = 1.27-4.59), but disappeared when further adjusted for APOEε4 status. PICALM rs561655 (G) (OR = 0.52, 95%CI = 0.30-0.92) and NOS3 rs1549758 (T) (OR = 0.53, 95%CI = 0.30-0.94) were identified as protective genetic factors of MCI for the first time in dominant model combined with the APOEε4 allele. Moreover, MTHFR rs1801133 (A) and CLU rs9331888 (G) showed more susceptibility to MCI in the additive model. SORL1 rs641120(G) showed a protective effect, whereas BIN1 rs5733839 consistently showed a risk effect for MCI in the overdominant model, regardless of APOEε4 status. This study suggests that some AD-associated SNPs are associated with cognitive decline and may have important implications for future studies. Show less

The pathological mechanism of Alzheimer's disease (AD) is complex. The binding of Aβ to α7 nicotinic acetylcholine receptor (α7nAChR) contributes to neuronal damage. Sinomenine (SIN) is an alkaloid extracted from the traditional Chinese medicine Qingfengteng (Sinomenium acutum). The anti-inflammatory, antioxidant, and immunomodulatory effects of SIN were confirmed to be closely associated with the α7nAChR. This study aimed to investigate whether α7nAChR serves as a pharmacological target of SIN against AD, and to evaluate the neuroprotective effects of SIN both in vivo and in vitro, focusing on the α7nAChR/Nrf2/Keap1 signaling pathway. In this study, the effects of SIN in both APP/PS1 transgenic mice and SH-SY5Y cells subjected to Aβ1-42-induced injury were assessed. The selective antagonist α-bungarotoxin ‌(α-BTX), the agonist nicotine (Nic) of α7nAChR, and α7nAChR siRNA were employed. The cognitive function, Aβ deposition, synaptic plasticity markers, the tau protein phosphorylation, mitochondrial membrane potential, oxidative stress and the α7nAChR/Nrf2/Keap1 signaling pathway were analyzed in vivo and/or in vitro. SIN significantly enhanced learning and memory abilities in APP/PS1 mice, reduced Aβ plaque deposition and synaptic dysfunction, and inhibited hyperphosphorylation of tau protein and oxidative stress in the brain. In Aβ1-42-induced neuronal injury model, SIN alleviated apoptosis, increased BDNF and ACh levels, inhibited mitochondrial damage, stabilized calcium homeostasis, and suppressed oxidative stress. Meanwhile, SIN disrupted Nrf2-Keap1 binding to promote the Nrf2/HO-1 signaling pathway. Nevertheless, SIN effects above were inhibited by α-BTX. The knockdown of α7nAChR in vitro significantly promoted Nrf2/HO-1 pathway and BDNF expression. SIN exerts neuroprotective effect in APP/PS1 transgenic mice and Aβ1-42-induced neuronal injury by inhibiting oxidative stress via α7nAChR/Nrf2/Keap1 pathway. This study provides evidence for α7nAChR as a new target and the clinical application potential of SIN in AD treatment. Show less

Depressive disorders often show recurrent courses that cannot be sufficiently prevented by existing therapeutic protocols. In other affective disorders, recurrence has been linked to three mechanisms -spontaneous recovery, accelerated new/relearning, and reinstatement- which are related to the preservation of disorder-related memory traces even through successful extinction-based interventions. Reconsolidation-interference protocols aim to directly alter such traces by reactivating and destabilizing them before intervention. While this approach has shown benefits in fear, craving, and trauma-related symptoms, its application to depression remains untested. To our knowledge, this study provides the first experimental evidence of its utility in depression-like states. Sixty participants took part in a three-day, three-group, double-blind randomized controlled trial. On day one, helplessness was induced using a modified unsolvable anagram task. On day two, participants were randomized into three groups undergoing different interventions while completing another cognitive demanding task: (1) extinction, where participants experienced success from start to finish; (2) reconsolidation, where participants briefly reexperienced failure before succeeding; or (3) reactivation, where failure repeated. On day three, the helplessness task was presented again to evaluate susceptibility for recurrence across conditions. Behavioral, self-report, and EEG data were collected. Across test days, participants showed reduced motivation and performance, attributing failure to personal ability, confirming successful helplessness induction. However, interventions at day two produced no robust group differences on behavioral, self-report, or EEG measures. Exploratory analyses suggested that brain-derived neurotrophic factor (BDNF) levels may have mediated outcomes. Findings do not confirm reconsolidation-based behavioral interference as effective for depression-like helplessness. Nonetheless, exploratory results highlight BDNF as a potential mediator, warranting further study on its role in postretrieval extinction effects in depression. Show less

Inflammation is increasingly implicated in the pathophysiology of mood and psychotic disorders. Integrating blood biomarkers and brain imaging may help uncover mechanistic pathways and guide targeted interventions. To identify shared and distinct multivariate patterns of peripheral inflammation and gray matter volume (GMV) in early-stage depressive and psychotic disorders using a transdiagnostic machine learning approach. The naturalistic multicenter PRONIA study was conducted between February 2014 and May 2019 with a follow-up period of up to 36 months; baseline data were analyzed between August 2021 and April 2024. Eight sites, including inpatient and outpatient facilities, in 5 European countries (Germany, Italy, Switzerland, Finland, and the United Kingdom) were included. The study included individuals with recent-onset depression (ROD, n = 163) or psychosis (ROP, n = 177) or clinical high-risk states for psychosis (CHR-P, n = 172), all with minimal medication exposure, and healthy control (HC) individuals (n = 166). Structural magnetic resonance imaging (MRI), peripheral assays of cytokines (eg, interleukin [IL] 6, IL-1β, tumor necrosis factor [TNF] α, C-reactive protein [CRP], brain-derived neurotrophic factor [BDNF], S100 calcium-binding protein B [S100B]); clinical assessments; neurocognitive testing. After data collection, sparse partial least squares was used to identify latent brain-blood signatures. Support vector machine classification evaluated psychosocial and neurocognitive predictors of signature expression using repeated nested cross-validation. A total of 678 participants (346 [51.0%] female; median [IQR] age, 24.0 [20.9-28.9] years) were included. Four signatures were identified. A psychosis signature (ρ = 0.27; P = .002) differentiated ROP from CHR-P with elevated IL-6, TNF-α, and reduced CRP, alongside GMV shifts in corticothalamic circuits. A depression signature (ρ = 0.19; P = .02) differentiated ROD from HC individuals with elevated IL-1β, IL-2, IL-4, S100B, and BDNF and GMV reductions in limbic regions. Additional signatures reflected age (ρ = 0.67) and sex or MRI quality (ρ = 0.53). Psychosocial features, including a differential childhood trauma pattern, predicted both the psychosis (balanced accuracy [BAC] = 67.2%) and depression (BAC = 78.0%) signatures. Cognitive performance predicted only the psychosis signature (BAC = 65.1%). In this study, early-stage depression and psychosis exhibited distinct neurobiological signatures involving immune and neuroanatomical markers, challenging fully dimensional disease models. These signatures are shaped by childhood trauma and cognition and may support biologically informed early interventions. Show less

Depression is a prevalent mental disorder in modern society, with a complex and incompletely understood etiology. Accumulating evidence indicates that pesticide exposure is a potential risk factor for mental health disorders. Atrazine (ATR), a widely used herbicide with the highest global application rates and frequently detected in environmental media, has been confirmed to possess neurotoxicity. However, there are currently no reports examining its effects on depression. Therefore, this study aimed to investigate the effects of subchronic ATR exposure on depression-like phenotypes in mice through behavioral tests, pathological examinations, and molecular analyses. The results demonstrated that ATR exposure induced significant depressive-like behaviors and led to neuronal reductions in key brain regions associated with depression, such as the hippocampus and prefrontal cortex. These effects were mechanistically linked to oxidative damage and decreased expression levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF). Collectively, this study not only reveals the potential role and mechanism of ATR as an environmental risk factor for depression, but also provides a theoretical basis for the prevention and treatment of its new neurotoxicological effects and future related research. 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

Hippocampal neuroinflammation (HNF) is a key pathological feature in neurodegenerative disorders. Milk-derived exosomes, as bioactive extracellular vesicles, have underexplored potential in regulating brain neuroinflammatory responses. This study aimed to characterize desert milk exosomes (D-Exo) and investigate their neuroprotective and anti-neuroinflammatory effects in LPS-induced HNF mice model and an LPS-stimulated BV2 microglia. Exosomes were isolated from desert and non-desert milk (ND-Exo) for proteomic analysis. After pretreating BV2 cells with exosomes and stimulating with LPS, their inflammatory responses and polarization were assessed by RT-PCR. Balb/c mice were orally gavaged with D-Exo or 0.9% NaCl for 28 days before LPS injection. Cognitive function was assessed via behavioral tests, with microglial/astrocyte activation analyzed by immunofluorescence. D-Exo exhibited superior stability and a unique proteomic profile enriched with proteins linked to neuroinflammation and blood-brain barrier (BBB) integrity, notably within the AMPK signaling pathway. In vitro, D-Exo shifted LPS-stimulated microglia from the M1 to the M2 phenotype. In vivo, it alleviated HNF and cognitive decline, reduced Aβ D-Exo is enriched with specific proteins, attenuates neuroinflammation and cognitive decline by regulating microglial M1/M2 polarization and AMPK pathway, highlighting its preventive potential. Show less

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive loss of cognitive function. Its main pathological features include accumulation of Amyloid-beta (Aβ) plaques, excessive phosphorylation of microtubule-associated protein tau (tau protein), and neuroinflammation. In recent years, studies have confirmed intestinal flora is closely connected to AD. Gut-brain axis has an important part in AD. Intestinal flora can achieve signal communication between gut and brain through metabolic, immune, neural, and endocrine pathways, thereby slowing down AD. It has been discovered that exercise is not only beneficial to physical health but also has a positive impact on the brain function. In recent years, more and more studies have found exercise can alleviate AD through the following four major pathways: regulating the diversity of intestinal flora, strengthening the blood-brain barrier (BBB), regulating immune homeostasis, and upregulating the brain-derived neurotrophic factor (BDNF). In this review, we have summarized intestinal flora in AD and systematically expounded potential regulatory pathways of exercise in modulating intestinal flora for AD. This provides a more theoretical basis for subsequent research targeting "gut-brain axis" to regulate AD. At the same time, this review also summarizes differences in different exercise types on improving intestinal flora for alleviating AD, providing new ideas and strategies for AD. 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

An increasing number of stroke survivors are burdened by persistent disabilities, requiring long-term rehabilitation. However, the extent of functional gain is highly variable, severely impairing patients' quality of life. This variability highlights a critical gap in current prognostic tools, which rely primarily on clinical and neuroimaging data. The aim of this review is to synthesize the current literature on serum biomarkers in stroke survivors and to evaluate their prognostic value for rehabilitation outcomes. Our synthesis indicates that biomarkers reflecting distinct pathophysiological processes are emerging as key prognostic indicators. Markers of inflammation such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and Interleukin-1 beta (IL-1β), and neuro-glial injury, including S100 Calcium-Binding Protein B (S100B), Neuron-Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), and Neurofilament Light Chain (NfL), are consistently associated with poorer functional outcomes. Conversely, markers of neuroplasticity, such as Brain-Derived Neurotrophic Factor (BDNF) and Insulin-like Growth Factor-1 (IGF-1), serve as potential indicators of recovery potential, although their predictive accuracy remains inconsistent across studies. Furthermore, emerging biomarkers of synaptic activity, such as Syntaxin-1a (STX1A) and Synaptosomal-Associated Protein, 25kDa (SNAP-25), and neuromuscular junction integrity, such as C-terminal Agrin Fragment (CAF), offer novel insights into brain-periphery communication, though their clinical utility is still under investigation. While promising, the translation of these biomarkers into clinical practice is hindered by methodological limitations, including assay heterogeneity and lack of large-scale validation. Future standardization of these molecular signatures is a critical step toward implementing precision medicine in stroke rehabilitation. Show less

Among ground-based paradigms used to reproduce altered gravity exposure, the hindlimb unloading (HU) model is widely employed to simulate microgravity conditions by removing gravitational loading from the hindlimbs. Despite its extensive use, behavioral adjustments during suspension remain poorly characterized, although they may provide valuable indicators of animal welfare and individual susceptibility. Here, we comprehensively characterized the behavioral profile of mice during and after HU using a dedicated ethogram, with the aim of identifying behavioral markers associated with individual coping strategies. Several exploratory and postural behaviors showed marked time-dependent modulation, with baseline exploratory activity predicting a more adaptive behavioral trajectory during suspension, possibly indicative of greater resilience. In parallel, brain levels of the neurotrophins NGF and BDNF were measured to explore their relationship with behavioral outcomes. Although no significant group differences were detected, suspended mice displayed a progressive reduction in both neurotrophins over time, which paralleled behavioral adaptation. Together, these findings indicate that specific exploratory behaviors represent reliable predictors of resilience to HU, while NGF and BDNF may reflect ongoing neuroplastic processes associated with prolonged suspension. Show less

Endometriosis (EDT) is a chronic, estrogen-dependent disease characterized by inflammation, fibrosis, pelvic pain, and infertility. Current therapies show limited long-term efficacy and adverse effects, underscoring the need for novel therapeutic approaches. Elevated copper (Cu) levels have been reported in both patients and animal models of EDT, making Cu chelation a promising strategy. This work aimed to evaluate the impact of ammonium tetrathiomolybdate (TM) on the expression of markers related to the interconnected processes of inflammation, innervation, and fibrogenesis in mice with induced EDT. Twenty-four female C57BL/6 mice were assigned to Sham, EDT, or EDT+TM groups. Treatment with TM began on postoperative day 15, with samples collected one month after EDT induction. Peritoneal fluid cytokines (TNF-α, IL-1β, IL-6, TGF-β1) were quantified by ELISA. Endometriotic-like lesions were examined for mRNA expression of cytokines, neurotrophins ( Show less

Brain-derived growth factor, BDNF, has critical roles in a wide variety of neuronal aspects, including cell survival, differentiation, and synaptic function after their maturation. TrkB, a high-affinity receptor for BDNF, is a major contributor in these neuronal aspects, and its functions are exerted via stimulating intracellular signaling pathways including the mitogen-activated protein kinase (MAPK) pathways. As a family of MAPKs, the functions of ERK1/2, p38MAPK, and JNKs have been extensively studied using in vivo and in vitro neuronal systems. ERK 1/2, a major serine-threonine kinase and belonging to the MAPK family, also works as a downstream molecule after activation of the BDNF/TrkB system. Interestingly, growing evidence has demonstrated that ERK1/2 signaling exerts a positive or negative influence on neurons in both healthy and pathological conditions in the central nervous system (CNS). Indeed, activation of ERK 1/2 stimulated by the BDNF/TrkB system is involved in the regulation of synaptic plasticity. On the other hand, overactivation of ERK1/2 signaling under pathological conditions is closely related to neurodegeneration. Furthermore, cell stress activates p38MAPKs and JNK signaling, contributing to the progression of neurodegeneration. In this review, we show how MAPK pathway signaling affects neuronal fate, including cell survival or cell death, in the CNS. Moreover, we discuss the involvement of overactivation of MAPK signaling in the neurodegeneration observed in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). 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

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

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

Major depressive disorder (MDD) is a leading cause of global morbidity and mortality. Although pharmacological treatments are widely used, their effects are often limited, and nearly half of patients show resistance to current antidepressants, including those unresponsive to all available therapies. These challenges highlight the need to better understand the neurobiological mechanisms driving MDD and to develop novel therapeutic strategies, especially those involving natural compounds with multitarget actions. Baicalin, a bioactive flavonoid from Show less

The global aging population has led to a rising prevalence of cognitive impairment, posing a significant public health challenge. Resistance training (RT) is a non-pharmacological intervention that has been increasingly investigated for its potential to support cognitive function in older adults. Clinical evidence suggests that RT may be associated with benefits in certain cognitive domains, including memory, executive function, processing speed, and visuospatial ability. However, findings across studies remain heterogeneous, with several trials reporting neutral outcomes. Most intervention studies involve structured RT programs conducted at moderate to high intensity and performed multiple times per week. However, optimal training parameters have not yet been clearly established due to variability in study design and the absence of formal dose-response analyses. Emerging evidence suggests that the cognitive effects of RT may be mediated, at least in part, through muscle-brain axis signaling involving exercise-induced myokines. Factors such as irisin, brain-derived neurotrophic factor, interleukin-6, interleukin-15, and insulin-like growth factor-1 have been implicated in processes related to neuroplasticity, neuroinflammatory regulation, and neurovascular function, primarily based on preclinical and translational research. This review synthesizes current evidence on RT-related molecular mechanisms and clinical findings to provide an integrative perspective on the potential role of resistance training in mitigating age-related cognitive decline. Show less