📋 Browse Articles

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

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

Benign prostatic hyperplasia (BPH) is a common public health problem in ageing men worldwide. Diarylpropionitrile, a selective ERβ agonist, favorably regulates cell proliferation and inflammation, two major hallmarks of BPH pathology. This study aimed to explore the mitigative impact of diarylpropionitrile on testosterone-driven BPH in rats. 40 Sprague Dawley male rats aged 2.5-3 months were randomly divided into 4 groups (n = 10): a normal control group, a testosterone-induced BPH group, a finasteride-treated group, and a diarylpropionitrile-treated group. BPH was induced by daily subcutaneous testosterone injections for 4 weeks, with finasteride and diarylpropionitrile administered orally once daily for the same duration, one hour before each testosterone injection. After 4 weeks of treatment, macroscopic and microscopic features of prostatic hyperplasia and androgenic, proliferative, angiogenic, apoptotic, and inflammatory biomarkers in prostatic tissue homogenates were assessed. Testosterone administration significantly increased prostate weight, prostatic index, and hyperplasia scores, while treatment with either diarylpropionitrile or finasteride effectively ameliorated these testosterone-induced changes. Both treatments significantly lowered elevated prostatic DHT, 5αR2, β-catenin, and PCNA levels, demonstrating a strong anti-proliferative effect. They also attenuated the increased pro-inflammatory cytokines IL-6, IL-27, and PGE2 and growth factors TGF-β and VEGF. Furthermore, both agents inhibited testosterone-induced ERβ upregulation and increased expression of the anti-apoptotic protein BCL2. There were no substantial differences comparing finasteride and diarylpropionitrile in the majority of the tested parameters. Diarylpropionitrile alleviates testosterone-driven BPH in rats by modulating key pathways associated with cellular proliferation and inflammation. Diarylpropionitrile, as an ERβ agonist, represents a promising alternative for the BPH treatment through multi-targeted mechanisms. 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

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

On the basis of life-style changes and statins, current guidelines recommend early combination therapy to reduce LDL cholesterol (LDL-C). Available and future novel non-statin lipid-lowering therapies may have specific advantages in patients with (1) statin intolerance, (2) elevated triglyceride-rich lipoproteins, (3) elevated lipoprotein(a), and (4) rare genetic dyslipidemias. Currently available treatment options to lower LDL-C with proven cardiovascular benefit include statins, ezetimibe, bempedoic acid, and PCSK9 antibodies. The 2025 update of the ESC/EAS dyslipidemia guidelines incorporates recommendations on early combination treatment and management of rare dyslipidemias, which are detailed in this review. Novel LDL-C-lowering strategies, targeting PCSK9 and CETP, may further improve dyslipidemia management. Drugs in development with profound effects on lipoprotein(a) or triglyceride concentration may allow for specific modification of residual cardiovascular risk. Innovative DNA-targeting therapies are moving towards clinical testing in larger studies. Various treatment options for patients with dyslipidemia and distinct characteristics have become available. Future developments may allow for even more tailored treatment, depending on dyslipidemia phenotype. 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

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

Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate the therapeutic potential of two dietary antioxidants-astaxanthin and 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

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

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

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. Among the genetic risk factors linked to AD, the Apolipoprotein E4 (ApoE4) remains the strongest. It is well known that carrying the ApoE4 isoform is associated with advanced AD pathology, blood-brain barrier (BBB) disruption, and changes in lipid metabolism. In this review, we provide an overview of the role of centrally and peripherally produced ApoE in AD. After this introduction, we focus on new findings regarding ApoE4's effects on AD pathology and BBB function. We then discuss ApoE's role in lipid metabolism in AD, highlighting examples of lipid changes caused by carrying the ApoE4 isoform. Next, the review explores the implications of ApoE4 isoforms for current treatments-whether they involve anti-amyloid therapy or other pharmacological agents used for AD-emphasizing the importance of personalized medicine approaches for patients with this high-risk allele. This review aims to provide an updated overview of ApoE4's effects on AD pathology and treatment. By integrating recent discoveries, it underscores the critical need to consider ApoE4 status in both research and clinical settings to enhance therapeutic strategies and outcomes for individuals with AD. 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

Cardiovascular disease (CVD) is influenced by disturbances in lipoprotein composition and metabolism, including triglyceride-rich lipoproteins (TRLs) and elevated lipoprotein (a) (Lp(a)). While interactions between Lp(a) and very-low-density lipoproteins (VLDL) have been studied in hypertriglyceridemic and CVD populations, data in normotriglyceridemic individuals without CV events are limited. Seventy normotriglyceridemic adults with triglycerides < 150 mg/dL and no CV events were enrolled and divided into two groups based on Lp(a) concentration: <30 mg/dL and ≥30 mg/dL. VLDL was isolated by ultracentrifugation, and concentrations of Lp(a), lipids (triglycerides, cholesterol), and apolipoproteins (apo B, apo C-II, apo C-III, apo E) were measured in serum and VLDL. Serum lipid and apolipoprotein concentrations did not differ between the groups. Individuals with Lp(a) ≥ 30 mg/dL had significantly higher VLDL concentrations of triglycerides (+71%), cholesterol (+54%), apo B (+28%), apo C-II (+36%), and apo C-III (+33%). Ratios of lipids and apolipoproteins to apo B indicated unchanged VLDL particle composition, suggesting that differences reflected increased particle number rather than altered composition. In normotriglyceridemic subjects with Lp(a) ≥ 30 mg/dL, VLDL particles are more abundant but compositionally unchanged. Redistribution of lipids and apolipoproteins toward VLDL may contribute to VLDL residual cardiovascular risk, underscoring the need for further studies on VLDL-Lp(a) interactions. Show less

Tail fat deposition constitutes a distinctive adaptive phenotype in sheep. The Large-tailed Han (LTH) and Small-tailed Han (STH) breeds display pronounced divergence in tail fat storage, offering an ideal model for elucidating lipid metabolism regulation. Integrated sRNA-Seq and RNA-Seq analysis identified 521 differentially expressed genes and 144 miRNAs, which were significantly enriched in lipid metabolism pathways, including fatty acid metabolism and PPAR signaling. Key candidate genes ( 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

Previous studies have shown that plasma amyloid-beta oligomers (AβOs), the toxic form of amyloid-beta (Aβ), are a critical issue in the development or worsening of Alzheimer's disease (AD) and can be regarded as a blood marker for screening in dementia. We examined plasma AβOs with their related biomarkers in a case-control study to clarify these issues. A total of 16 patients diagnosed with Alzheimer's dementia (AD) and 16 cognitively normal controls (NCs) were recruited to compare their plasma biomarkers, AβO, Aβ Show less

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by decreased amyloid-beta (Aβ) clearance, enhanced Aβ aggregation, an increased risk of amyloid-related imaging abnormalities (ARIA), and blood-brain barrier (BBB) dysfunction. The 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

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

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