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Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary atherosclerosis. Functional aspects of high-density lipoprotein (HDL), including cholesterol transfer capacity, may contribute to cardiovascular risk heterogeneity in FH. To investigate whether cholesterol transfer to HDL and other HDL-related parameters are associated with coronary artery disease (CAD) in patients with heterozygous FH (HeFH). Fifty-three genetically confirmed FH patients (mean age: 49.2 years; 73.6% female) were included. Twenty-seven had plaques, while 26 had no vessel abnormalities as determined by coronary computed tomography angiography. The transfer of both unesterified and esterified cholesterol (UC and EC) to HDL, as well as HDL antioxidant capacity, particle size, and subfractions, plasma concentrations of cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON-1) activity were assessed. Family history of premature CAD (P < .028) and tendinous xanthomas (P = .014) were more frequent in those with plaques. No differences were found in apolipoprotein (apo) B, LDL-C, LDL-C year score, lipoprotein(a), non-HDL-C, apo A-I, HDL-C, HDL subfractions, or triglycerides. Transfer of lipids to HDL and antioxidant capacity did not differ between the groups. LCAT concentrations and PON-1 activity were also similar. In contrast, CETP concentration was higher in those with plaques (P < .008). However, only family history of early CAD (odds ratio [OR]: 4.12, 95% CI, 1.23-13.80, P = .022) and xanthomas (OR: 3.65, 95% CI, 1.06-12.60, P = .040) were independently associated with plaques. Among patients with HeFH, no HDL-related parameter was independently associated with subclinical CAD. 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

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

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

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

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

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

Despite the widespread use of lipid-lowering therapies, a significant proportion of patients with atherosclerotic cardiovascular disease fail to achieve the recommended LDL-cholesterol targets, thus remaining at high residual risk. Inhibition of cholesteryl ester transfer protein (CETP) has long been considered a pharmacological strategy, but has historically been hindered by clinical failures. Obicetrapib, a next-generation CETP inhibitor, has recently shown promising results in terms of efficacy and safety. This review critically examines the physiology of CETP, the negative outcomes of earlier CETP inhibitors, and the emerging evidence on obicetrapib, highlighting the potential role of this molecule in the treatment of hypercholesterolemia and in the secondary prevention of atherosclerotic cardiovascular disease. 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

Lipoprotein(a) [Lp(a)] is recognized as a cardiovascular risk indicator; however, its connection to peripheral arterial disease (PAD) in individuals with type 2 diabetes mellitus (T2DM) is not well established. This research seeks to explore how Lp(a) concentrations relate to the occurrence of PAD in T2DM patients. A retrospective analysis was conducted on 590 patients diagnosed with T2DM who were admitted to Hefei First People's Hospital from January 2022 to August 2024. Participants were grouped into tertiles according to their Lp(a) levels. The diagnosis of PAD was made using the ankle-brachial index (ABI), with an ABI <0.9 considered indicative of PAD. The association between Lp(a) concentrations and PAD was examined using multivariate logistic regression models, subgroup analyses, receiver operating characteristic (ROC) curves, and restricted cubic spline (RCS) plotting. Compared to lower Lp(a) levels, the group with higher Lp(a) levels exhibited a higher prevalence of PAD ( A significant correlation was observed between elevated Lp(a) levels and an increased risk of PAD in patients with T2DM. Show less

Cholesteryl ester transfer protein (CETP) is a crucial therapeutic target for combating cardiovascular disease (CVD) due to its strong influence in modulating high-density lipoprotein (HDL) levels. CETP is responsible for the bidirectional transfer of cholesteryl esters (CEs) and triglycerides (TGs) between different lipoprotein fractions. Although CETP encounters both these neutral lipid substrates when it penetrates deep into lipoprotein cores and can acquire either lipid, prior studies have examined its conformational space only in the presence of CEs or TGs individually. Here, we investigate the uncharacterised dynamics of CETP in heterogeneous lipid environments (CE-TG and TG-CE) using molecular dynamics simulations. Compared to the stable, homogeneous CE-bound state, the introduction of TG, particularly in mixed CE/TG configurations, induces significant structural instability and protein expansion. Mixed-lipid occupancy leads to elevated flexibility in critical lipoprotein-binding loops and the distortion of vital secondary structural elements. Furthermore, large-scale collective motion analyses reveal that heterogeneous binding forces CETP into aberrant, asymmetric, and hyper-twisted conformations. This disrupts the symmetric bending-twisting balance essential for efficient lipid exchange. Free energy landscapes confirm that the TGs within the mixed-lipid systems exhibit varied conformational states and adopt orientations that deviate from their reported parallel N-N orientation for lipid transfer through CETP. These findings suggest that the simultaneous presence of CE and TG imposes considerable conformational strain, fundamentally impairing CETP's lipid transport mechanism and offering novel mechanistic insights for future CETP-targeted therapeutics. Show less

Atrial fibrillation (AF) is a progressive condition characterized by atrial remodeling and dysfunction. This systematic review explores biomarkers that predict new-onset AF, highlighting their potential to improve early diagnosis and risk stratification in high-risk patients, and prevention of stroke and major adverse cardiovascular events. We conducted a literature search of studies published between January 2014-November 2025 in PubMed, Scopus, Web of Science, and Google Scholar, following PRISMA 2020 guidelines. Studies analysing specific populations and patients with prior or postoperative AF were excluded. Quality was assessed using the Newcastle-Ottawa scale. Effect sizes were expressed as HR with 95% CIs. We included 10 cohort studies comprising 472,581patients and 35,271 (7.5%) new-onset AF. Overall, 18 biomarkers were associated with an increased risk of AF, most notably NT-proBNP and sVCAM-1. Conversely, 9 biomarkers were associated with a lower AF incidence, such as ADAMTS13 (HR 0.78, 95%CI 0.70-0.88). A meta-analysis of NT-proBNP demonstrated its association with a higher incidence of AF (HR 1.37, 95%CI 1.19-1.59) with high heterogeneity (I2 = 80%, p<0.01) and Lp(a) was associated with a significant 3% increase in AF incidence per 20 mg/dL increment. Two networks were constructed according to whether biomarkers were associated with a higher or lower incidence of AF, visualising their connection with other biomarkers. Well-known biomarkers, such as NT-proBNP, and others not yet incorporated into clinical practice, such as Lp(a) and sVCAM-1, could play a role in the diagnosis and preventive management of AF. Large-scale prospective studies are needed to validate and optimise their diagnostic utility in predicting new-onset AF. Show less

Maternal immune activation (MIA) is a key environmental risk factor for neurodevelopmental disorders such as schizophrenia. MicroRNAs are critical regulators of brain development, yet their role in MIA-induced pathology remains unclear. We found that miR-322-5p was significantly upregulated in the prefrontal cortex of MIA-exposed offspring and directly targeted the 3' untranslated region of brain-derived neurotrophic factor (BDNF), inhibiting its expression. This upregulation impaired BDNF/TrkB/AKT signaling and reduced the synaptic protein PSD95, leading to hypoactivity, cognitive deficits, social impairments, and disrupted sensorimotor gating. Inhibition of miR-322-5p or overexpression of BDNF in the prefrontal cortex restored signaling and reversed both behavioral and molecular abnormalities. These results identify miR-322-5p as a key mediator of MIA-induced neuropathology via repression of BDNF signaling and suggest its potential as a therapeutic target in neurodevelopmental disorders. 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

Obesity-related health issues, including cognitive decline linked to hippocampal neurogenesis and neuroplasticity, are gaining more attention as obesity rates rise worldwide. Physical activity is recognized as a potent stimulator of neurotrophic factors. This study examined the impact of six weeks of treadmill training on hippocampal molecular pathways in adult female Zucker diabetic fatty (obese) and Zucker lean rats. Animals were assigned to either treadmill exercise (n = 10) or sedentary control (n = 10) groups. Endurance training (ET) markedly upregulated mRNA expression of brain-derived neurotrophic factor and its receptor. The PI3K/Akt pathway was upregulated only in the trained lean rats and downregulated in the trained obese group compared with sedentary controls. ET elicited divergent effects on neurotrophin-associated PLCγ/PKC/CAMKII signalling between lean and obese groups. Sedentary obese rats primarily utilized the PLCγ/PKC axis, while both trained groups (lean and obese) showed increased CAMKII expression, associated with enhanced synaptic plasticity and memory. Enhanced synaptophysin mRNA indicated improved synaptogenesis and plasticity following ET. Trained obese rats also exhibited reduced expression of the microglial pro-inflammatory marker Iba1, alongside increased markers of oligodendrocyte regeneration and neurofilament expression. Behavioral assessment via the passive avoidance test demonstrated improved learning and memory in trained obese animals. Collectively, these findings suggest that ET may mitigate obesity-induced hippocampal damage, exert neuroprotection, and enhance hippocampal function. Show less

The vital role of brain-derived neurotrophic factor (BDNF) in neuronal development, synaptic plasticity, and neuroprotection has been explored for decades. Therefore, the expression, processing, and signalling activities of this neurotrophin, which is reliant upon TrkB and p75NTR receptors, have been well characterised in both health and disease. This review summarises the latest findings on BDNF dysregulation in neuropathologies. Indeed, across diseases of both the central and peripheral nervous systems, BDNF signalling is frequently disrupted, contributing to neuronal dysfunction and degeneration. Consequently, through direct or indirect enhancement of its expression and/or function, BDNF has proved to be a promising therapeutic target across many neurological conditions. However, the complexity of its regulation and interaction with several different receptors underpins the need for further research to deepen our understanding of BDNF disruption in neuropathologies and to achieve its therapeutic potential. Show less

Hypercholesterolemia is a major risk factor for cardiovascular disease, necessitating the development of effective and safe lipid-lowering interventions. This study evaluated the antihypercholesterolemic effects of KGC11 Show less

Schizophrenia is a complex mental disorder involving genetic, environmental, and neurodevelopmental factors. Despite significant progress in identifying several genetic contributors to schizophrenia, the role of apolipoprotein in lipid metabolism, neurodevelopment, and neuroprotection remains underexplored. This systematic review aims to synthesise existing genetic studies on apolipoproteins associated with schizophrenia to clarify their potential role in the disorder's pathogenesis. A comprehensive literature review was conducted using the PubMed and Scopus databases, involving studies published from 2004 to 2023, and limited to English. Keywords included "schizophrenia," "apolipoprotein," "genetic," and "genetics." Non-research publications such as books, reviews, editorials, letters to editors, short communications, book series, chapters, and conference proceedings were excluded from this review. Only peer-reviewed journal articles were selected to ensure the reliability and credibility of the systematic review. A total of 41 articles were included in the review, with four key themes identified. The themes addressed specific aspects of apolipoproteins in schizophrenia, including their role in schizophrenia susceptibility, lipid metabolism, and cognitive functions within the disorder. This review presents a novel synthesis of these studies, focusing on the underexplored roles of apolipoprotein genes, including APOE, APOL, APOD, APOA, APOC, APOER2, and APOBEC, in schizophrenia. This systematic review provides a comprehensive understanding of the genetics of apolipoprotein in schizophrenia, particularly in relation to lipid metabolism. The findings suggest future research directions to enhance the understanding of schizophrenia pathogenesis and highlight the importance of targeted research to identify specific genetic biomarkers for therapeutic interventions. Show less

Exercise is a potent modulator of mental health, with accumulating evidence highlighting its ability to produce structural and functional changes in the brain. This review synthesizes findings across neurobiological, molecular, and systemic domains to explain how exercise improves outcomes in mood, anxiety, and stress-related disorders. We examine how exercise stimulates brain-derived neurotrophic factor (BDNF), regulates monoaminergic systems (serotonin, dopamine, norepinephrine), modulates inflammatory and oxidative stress pathways, and promotes neurogenesis and synaptic plasticity. The review also explores systemic mechanisms including the gut-brain axis, myokine signaling (e.g., irisin, cathepsin B), and the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, we discuss how exercise influences key psychological mechanisms, including emotion regulation, self-efficacy, and cognitive reappraisal, offering a translational bridge between physiology and psychotherapy. Understanding these overlapping mechanisms can guide clinicians in prescribing exercise as an evidence-based adjunct or standalone therapy for mental health disorders. This model of exercise as medicine has the potential to enhance both accessibility and efficacy of mental health care. Implications for clinical integration, mechanistic research, and policy development are discussed. Show less

A converging mechanistic theme across mental disorders involves impaired neuroplasticity and reduced brain-derived neurotrophic factor (BDNF). Glucagon-like peptide-1 receptor agonists (GLP-1RAs), used for type 2 diabetes and obesity, have shown neuroprotective potential, but whether these effects are mediated by BDNF is unclear. This systematic review synthesised molecular evidence linking GLP-1RA administration to BDNF changes and evaluated their contribution to illness progression in neurodegenerative and psychiatric disorders. A systematic search of PubMed, Ovid and Google Scholar from inception to September 6, 2025, identified studies reporting BDNF-related outcomes following GLP-1RA treatment. Eligible studies included primary in vivo or in vitro research on GLP-1RAs in models of neurodegenerative or psychiatric disorders. Risk of bias was assessed using SYRCLE and QUIN tools. The initial search yielded 300 records, of which 18 met the inclusion criteria. Across these studies, GLP-1RAs consistently enhanced BDNF expression and signalling in models of diabetes, neurodegeneration and neurotoxicity, with diabetic models included for their relevance to GLP-1RA pharmacology and shared neuroinflammatory pathway. Reported increases in BDNF expression ranged from 76 % to 377 %, correlating with improved synaptic plasticity, cognition and neuronal survival. In vitro, GLP-1 and exendin-4 increased BDNF expression and axonal transport even under Aβ oligomer exposure. While most neuroprotection aligned with BDNF upregulation, some effects occurred independently through alternative pathways. GLP-1RAs upregulate BDNF in preclinical models, supporting its role as a key mediator of neuroprotection. Despite some BDNF-independent actions, the consistent restoration of neurotrophic support positions BDNF as a central pathway for disease modification. 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

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

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

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

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

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

Data are limited regarding national clinician awareness, testing, and treatment of lipoprotein(a) [Lp(a)]. We conducted a national survey of US clinicians to investigate these issues. An internet-based survey of awareness, testing and treatment of Lp(a) was administered by a medical survey company to clinicians who have been in practice ≥5 years in the US or its territories. 2002 clinicians completed the survey: 47 % were primary care, 35 % cardiology, 9 % endocrinology, and 9 % neurology. 28 % were female, 24 % Asian, 4 % Hispanic, and 3 % Black. Most clinicians agree knowing the Lp(a) level can improve risk assessment and patient engagement. Patients with premature or recurrent CVD events are most likely to be targeted for Lp(a) testing and for prescribing possible future Lp(a)-targeted therapies. Show less

Major depressive disorder (MDD) is a prevalent and disabling psychiatric condition in Saudi Arabia, with genetic susceptibility remaining incompletely characterized. Reduced brain-derived neurotrophic factor (BDNF) activity has been implicated in MDD. The Val66Met polymorphism (rs6265), involving the substitution of valine (Val, G allele) with methionine (Met, A allele), impairs activity-dependent BDNF secretion. This study examined the frequency of Val66Met and its association with MDD in a Saudi cohort. A case-control study was conducted, including 87 patients with MDD (44 males, 43 females; mean age 44.2 ± 11.5 years) and 87 healthy controls (39 males, 48 females; mean age 28.7 ± 8.4 years). Genotyping was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction. Unadjusted and age- and sex-adjusted logistic regression analyses were applied under genotype-specific, dominant, recessive, and allelic models. The Val/Val (GG) genotype was more frequent in controls than patients (54.0% vs. 34.5%), whereas the Met/Met (AA) genotype was detected exclusively in patients (21.8% vs. 0%; χ The BDNF Val66Met polymorphism is associated with MDD susceptibility in Saudis. The Met (A) allele, particularly in homozygosity, confers increased risk, while the Val/Val genotype appears protective, supporting population-specific genetic contributions to depression. Show less