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Longer-term effects of chiropractic care on neuroplasticity, stress, and immune biomarkers remain unclear. This study evaluates the effects of chiropractic care on physiological biomarkers, including brain-derived neurotrophic factor (BDNF), cortisol (saliva, blood, hair), and inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), C-reactive protein (CRP), B-lymphocytes (CD19), T-helper cells (CD4), cytotoxic T cells (CD8), and natural killer cells (CD56)] in subclinical spinal pain patients. Parallel-group, pragmatic randomized controlled trial conducted at the Rehabilitation Center of Railway General Hospital, Rawalpindi, Pakistan. Intervention: 12 weeks; follow-up: 16 weeks (May-December 2022). Participants with subclinical spinal pain were randomly assigned by using simple lottery method to either 12 weeks of chiropractic or sham care. We aimed to recruit up to 150 participants over three months; however, given the pragmatic nature of the trial and logistical constraints, including the availability of chiropractors, the final number enrolled was determined by how many eligible participants could be recruited during this time. Adults aged 20-60 years with subclinical spinal pain (n = 106 randomized; 88 completed 12-week measures; 73 completed 16-week follow-up). Among those who finished 12 weeks: chiropractic, 26 males/15 females, mean age 37.49 ± 12.39 years; sham, 24 males/23 females, mean age 26.85 ± 7.13 years. The primary outcome blood BDNF and secondary outcome, including saliva, blood and hair cortisol, IL-6, TNF-α, IFN-γ, CRP, CD19, CD4, CD8, and CD56 levels were measured at baseline, after 12 weeks of intervention, and at a 16-week follow-up. Linear and linear mixed-effects regression models were used to assess the effect of care and time on biological measures. Significant between-group differences were observed after 12 weeks of intervention, with higher salivary cortisol 5 ± 2 [0, 10], p = 0.045 and blood BDNF150 ± 60 (40, 270), p = 0.009 and IL-6 1.0 ± 0.3 [0.5, 1.5], p < 0.001 levels in the chiropractic care group. At the 16-week follow-up, blood cortisol -9 ± 4 [-17, -1], p = 0.024, IFN-γ - 22 ± 7 [-35, -9], and TNF-α -2 ± 1 [-5, 0], p = 0.028 levels increased in the sham group. Within-group comparisons showed a non-significant 10 ± 20 [-20, 50], p = 0.439 reduction in hair cortisol levels in the chiropractic group at 12 weeks, along with increased levels of blood cortisol, BDNF, CD8, CD4, IL-6, and CD19. 12 weeks of Chiropractic care modulates biomarkers linked to neuroplasticity, inflammation, and stress. Increases in brain-derived neurotrophic factor and interleukin-6 suggest enhanced neuroplasticity and inflammatory responses, while decreases in tumor necrosis factor-alpha indicate a regulatory effect on systemic inflammation. These findings support the notion that chiropractic care modulates physiological systemic biomarkers, which may underscore its benefits on clinical outcomes. ClinicalTrials.gov NCT05369156. Show less

The main objective of this study is to non-invasively investigate the relationship between metacognitive beliefs and cortisol, the primary stress output of the hypothalamic-pituitary-adrenal (HPA) axis, as well as neurotrophic factors associated with neuroplasticity brain-derived neurotrophic factor and neuron-derived neurotrophic factor (BDNF and NDNF). Within this framework, the hypotheses that negative metacognitions would be associated with increased cortisol and decreased BDNF levels, and that cortisol might play a mediating role in this relationship, were tested. The study was designed in a cross-sectional model with 60 university students. Participants' metacognitive beliefs were measured using the Metacognitions Questionnaire-30 (MCQ-30). Salivary cortisol, BDNF, and NDNF levels were analyzed using the ELISA method. Pearson correlation and hierarchical multiple regression analyses were used for data analysis. The results showed a significant positive relationship between the total metacognition score and cortisol (r = 0.589, p < 0.01) and a strong negative relationship between cortisol and BDNF (r = -0.662, p < 0.01). Hierarchical regression analysis supported a partial mediation model, indicating that dysfunctional metacognitive beliefs have both a significant direct negative association with BDNF and an indirect association mediated by cortisol. In the final model, both metacognition (β = -0.298, p < 0.05) and cortisol (β = -0.281, p < 0.05) were significant factors associated with lower BDNF levels. NDNF showed a positive relationship with BDNF (r = 0.571) but not with other variables. These findings point to a psychobiological model where dysfunctional metacognitive beliefs are linked to suppressed neuroprotective mechanisms like BDNF, both directly and indirectly through HPA axis activation. The results shed light on the potential neurobiological mechanisms underlying the effectiveness of metacognitive therapies. Show less

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, characterized by inflammation, demyelination, gliosis, and neuronal loss. Cognitive disorders are part of the clinical presentation, as well as in the early stages, with a prevalence rate ranging from 40 to 65% and are strictly associated with poor quality of life. In recent years, advances in the field of molecular biomarkers have contributed to improving the accuracy of cognitive diagnosis and to identifying subjects at risk of developing cognitive disorders. By focusing on longitudinal studies, this review aims to elucidate the temporal dynamics and potential predictive value of CSF and serum biomarkers in identifying cognitive decline and monitoring disease progression in MS. A systematic review was conducted using the PRISMA guidelines. 827 studies were identified by searching PubMed, Scopus, and Web of Science between July and August 2025. After screening, 8 studies fulfilled the eligibility criteria and were included. NfL showed heterogeneous results: some studies identified it as a feasible biomarker able to predict cognitive decline, while others did not. GFAP did not show significant correlations. Parvalbumin was longitudinally associated with poorer cognition and greater fatigue. Specific microRNAs (miR-126.3p, miR-9p) were associated with processing speed decline. Higher BDNF levels were linked to cognitive improvement. Other biomarkers (OPN, IL-6, CHI3L1, CXCL13) provided insufficient evidence. Findings add interesting contributions to the complex picture of the pathophysiology underpinning cognitive decline in MS. The most promising direction is the shift toward blood-based biomarkers, due to their minimally invasive nature and potential for clinical applicability, which may enable clinicians to anticipate, monitor, and potentially modify the cognitive trajectory of people living with MS. Show less

Evaluate the association between functional recovery and a panel of specific neuronal biomarkers, in a cohort of stroke patients. Serum levels of neuronal specific enolase (NSE), neurofilament light chain (NfL), brain derived neurotrophic factor (BDNF), amyloid-β Linear regression was performed to predict changes in clinical scales during follow up, according to baseline biomarkers levels. NSE at T0 was a significant predictor of improvement in FAC and RMI, where the higher the NSE concentration, the smaller the improvement. Therefore, baseline NSE explained 39% of the variation in FAC and 31% in RMI over time. No significant differences were observed with respect to other scales or other biomarkers. This exploratory study suggested that serum NSE may be a predictor of functional mobility recovery in post-acute stroke patients and represents a useful tool for patients' stratification. Show less

Aluminum ions are an immunostimulating agent and a promoter of the production of ROS that play a key role in the pathogenesis of age-related diseases. The severity of morphological signs of neurodegeneration caused by chronic intake of AlCl Show less

Gliomas are the most common malignant primary brain tumors in adults. The treatment of high-grade gliomas is very limited due to their diffuse infiltration, high plasticity, and resistance to conventional therapies. Although they were long considered passive massive lesions, they are now regarded as functionally integrated components of neural circuits, as they form authentic electrochemical synapses with neurons. This allows them to mimic neuronal activity to drive tumor growth and invasion. Ultrastructural studies show presynaptic vesicles in neurons and postsynaptic densities in glioma cell membranes, while electrophysiological recordings detect postsynaptic currents in tumor cells. Tumor microtubules (TMs), dynamic cytoplasmic protrusions enriched in AMPA receptors, are the structures responsible for glioma-glioma and glioma-neuron connectivity, also contributing to treatment resistance and tumor network integration. In these connections, neurons release glutamate that mainly activates their AMPA receptors in glioma cells, while gliomas release excess glutamate, causing excitotoxicity, altering the local excitatory-inhibitory balance, and promoting a hyperexcitable and pro-tumorigenic microenvironment. In addition, certain gliomas, such as diffuse midline gliomas, have altered chloride homeostasis, which makes GABAergic signaling depolarizing and growth promoting. Synaptogenic factors, such as neuroligin-3 and BDNF, further enhance glioma proliferation and synapse formation. These synaptic and paracrine interactions contribute to cognitive impairment, epileptogenesis, and resistance to surgical and pharmacological interventions. High functional connectivity within gliomas correlates with shorter patient survival. Therapies such as AMPA receptor antagonists (perampanel), glutamate release modulators (riluzole or sulfasalazine), and chloride cotransporter inhibitors (NKCC1 blockers) aim to improve outcomes for patients. Show less

Chronic pain is increasingly regarded as a condition of glia-neuronal dysregulation driven by persistent neuroinflammatory signaling. Following injury to nerves or tissues, glial cells, including astrocytes or satellite glial cells, undergo changes in their phenotype, thereby amplifying painful stimuli mediated by cytokines, chemokines, or ATP signaling. In response to injuries, activated microglia release several mediators such as BDNF, IL-1β, or TNF-α, thereby disrupting chloride homeostasis and inducing disinhibition in the dorsal horn, and sustaining maladaptive neuroimmune activity. Dysfunction of astrocytes, characterized by impaired glutamate clearance via excitatory amino acid transporter 2 and elevated C-X-C motif chemokine ligand 1 (CXCL1) and ATP release, drives neuronal sensitization, loss of neuroprotective metabolic support, and persistence of pain. In peripheral ganglia, connexin-43-mediated satellite glial cell coupling leads to hyperexcitability, resulting in neuropathic and orofacial pain and contributing to peripheral neuroinflammation. Presently, there is no unified framework for glial cell types, and the molecular mechanisms underlying microglial, astrocyte, and satellite glial cell contributions to the transition to chronic pain from acute pain are not completely elucidated. This review synthesizes current evidence on cellular and molecular mechanisms linking glial reactivity to pain chronification through sustained neuroinflammatory remodeling and impaired neuroprotection. It evaluates therapeutic strategies, including purinergic receptor P2X4 and toll-like receptor 4 antagonists, to metabolic reprogramming, exosome therapy, and neuromodulation, aimed at restoring homeostatic glial function and re-establishing neuroprotective glia-neuron interactions. A deeper understanding of the temporal and spatial dynamics of glial activation may enable personalized, non-opioid interventions that not only achieve durable analgesia but also prevent progressive neuroinflammatory damage and support long-term functional recovery. Show less

Deep brain stimulation (DBS) is an established therapy for motor symptom management in Parkinson's disease (PD), yet emerging evidence suggests that its effects may extend beyond functional circuit modulation to include cellular and molecular mechanisms with potential neuroprotective significance. This review synthesizes current evidence on the neuroprotective mechanisms of DBS, with an emphasis on preclinical and clinical studies that highlight its effects on neuronal survival, trophic support, oxidative stress, inflammation, synaptic plasticity, and network homeostasis. Preclinical data indicate that DBS reduces dopaminergic neuron degeneration, enhances brain-derived neurotrophic factor (BDNF) signaling, preserves mitochondrial function, attenuates neuroinflammation, and fosters synaptic remodeling. Clinical studies provide convergent, though less definitive, evidence from imaging, fluid biomarkers, and long-term outcomes supporting potential disease-modifying effects. These findings underscore a shift in the conceptualization of DBS from purely symptomatic relief toward modulation of underlying pathogenic processes. DBS holds promise as a neuroprotective therapy for PD, but critical gaps remain in validating these mechanisms in patients. Future directions include the development of biomarker-driven longitudinal studies, refinement of adaptive stimulation strategies, integration with adjunctive disease-modifying strategies, and exploration of personalized approaches based on molecular and network signatures. By bridging mechanistic understanding with translational innovation, DBS may evolve into a precision therapy capable of altering the progression trajectory of PD. Show less

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) ameliorate motor deficits in cerebral palsy (CP), but the effect of injection frequency remains unclear. Moreover, most studies have focused on mild CP models (unilateral carotid artery occlusion [UCAO] model). This study explored the effect and mechanism of hUC-MSCs in a rat model of moderate-to-severe CP (bilateral carotid artery occlusion [BCAO] model). On postnatal Day 4 (P4), Wistar rat pups underwent BCAO induction. Subsequently, they received either a single intrathecal injection of hUC-MSCs on P21 or repeated injections on P21, P28, P35, and P42. Motor performance was assessed using the rotarod and front-limb suspension tests, while neuronal regeneration and inflammation were evaluated via biomarkers including neuronal nuclear antigen (NeuN), ionized calcium-binding adapter molecule-1 (Iba-1), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and brain-derived neurotrophic factor (BDNF). P18 model screening confirmed that the BCAO model resulted in more severe brain damage and motor impairment than the UCAO model. After injection of lentivirally transfected hUC-MSCs, it was found that hUC-MSCs could nest in the damaged area and survive for at least 3 days. Administration of hUC-MSCs following BCAO modeling led to notable improvements in both behavioral performance and histological outcomes. Furthermore, repeated injections offered greater therapeutic benefits compared to single injection. It indicated that the efficacy of repeated injections of hUC-MSCs in the treatment of moderate-to-severe CP was superior to that of single injection. Its mechanism was related to the improvement of damaged myelin structure, reduced immunoinflammatory responses, and increased neurotrophic support. Show less

Major depressive disorder (MDD) is increasingly recognized as a disorder of impaired neuroplasticity and large-scale network dysfunction rather than a simple monoaminergic deficit. Converging evidence indicates that chronic stress and depression erode synaptic connectivity, reduce glial support, and destabilize functional interactions among the default mode, salience, and executive networks. Conventional antidepressants indirectly restore circuit function over weeks, but the advent of rapid-acting glutamatergic agents has opened a new path for targeting these abnormalities directly. In this narrative review, we synthesize molecular, cellular, and connectomic findings to outline a conceptual Connectomic Glutamate Framework of Depression. We first examine how NMDAR blockade and subsequent AMPAR facilitation activate mTORC1 and BDNF signaling, driving synaptogenesis and dendritic spine formation. We then highlight the role of astrocytes and microglia in shaping the "quad-partite synapse" and sustaining network integrity. Neuroimaging studies demonstrate that glutamatergic modulators remodel dysfunctional networks: dampening DMN hyperconnectivity, enhancing fronto-limbic coupling, and normalizing salience-driven switching. Integrating these domains, we propose a hypothesis-generating, two-phase model in which glutamatergic agents destabilize maladaptive attractor states and then reintegrate circuits through structural remodeling. This framework bridges molecules, cells, and networks, offering mechanistic insight into the rapid efficacy of glutamatergic antidepressants and highlighting priorities for clinical translation. Show less

Global cerebral ischemia (GCI) during childhood is a leading cause of long-term cognitive impairment, yet no therapies currently exist to promote recovery in survivors. We previously demonstrated that juvenile mice exhibit transient hippocampal synaptic dysfunction after GCI, associated with reduced brain-derived neurotrophic factor (BDNF) expression and partial endogenous recovery over time. In this study, we tested whether delayed treatment with fluoxetine (FLX)-a selective serotonin reuptake inhibitor (SSRI) known to enhance BDNF-TrkB signaling-could accelerate synaptic recovery. Juvenile mice underwent cardiac arrest and cardiopulmonary resuscitation, followed by in vivo FLX or vehicle administration from postinjury days 10-13. Electrophysiological recordings on day 14 revealed that FLX restored hippocampal long-term potentiation (LTP) in males but not females. This effect was paralleled by an increase in hippocampal BDNF expression in FLX-treated males, whereas no change was observed in females. Paired ex vivo experiments further confirmed that acute FLX exposure rescued LTP in GCI-injured male slices. These findings suggest that FLX promotes synaptic recovery through BDNF-TrkB signaling in males, while recovery in females may proceed via alternate, hormone-dependent mechanisms. Together, these results identify a novel therapeutic window for enhancing neuroplasticity after juvenile GCI and underscore the importance of developmental stage and biological sex in shaping responses to treatment. Show less

Aging is associated with a progressive decline in both cognitive and physical function, and neuroinflammation and metabolic dysregulation often exacerbate this decline, particularly in older women. This study investigated the effects of a 12-week intermittent combined exercise program on cognitive function, physical performance, and neurophysiological biomarkers in community-dwelling women aged 75 years and older. Forty participants were recruited from a local welfare center and randomly assigned to an exercise group (n=20) or a control group (n=20). The exercise group participated in three supervised sessions per week that integrated aerobic exercise, resistance exercise, functional exercise, and cognitive exercise. Cognitive domains (attention, language, and memory) were assessed using the Seoul Neuropsychological Screening Test-II. Physical function was assessed using the Geriatric Physical Fitness Test (chair stand, arm flexion, grip strength, and 6-min walk). Blood samples were analyzed to measure serum brain-derived neurotrophic factor (BDNF), interleukin (IL-6), tumor necrosis factor (TNF)-α, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Paired and independent Show less

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by repetitive behaviors and a lack of social communication. The role of probiotics, phytochemicals and their combination phytochemicals as treatment options for ASD is still under study. This study aimed to evaluate the associated molecular pathways and explore the impact of Fifty 3-week-old male albino rat pups were randomly distributed into five groups. The groups included a control group, a PA-induced ASD group, in which PA (250 mg/kg, p.o.) was administered for 3 days, and three other groups that received PA (250 mg/kg, p.o.) for 3 days along with either Compared with the group administered only PA, treatment with Our results suggest that Show less

Human excitatory neurons programmed through neurogenin-2 (NGN2) overexpression are widely used to model brain disorders in vitro. Although growth factors (GFs) such as BDNF, GDNF, NT3 and CNTF are commonly included in differentiation protocols, their individual and combined effects on neuronal survival, morphology and function remain insufficiently characterized. Here, we systematically examined the impact of these GFs, alone or in combination, on the development and maturation of NGN2-neurons. We also compare network activity of neurons maintained in Neurobasal medium (NBM) versus BrainPhys (PB). We show that BDNF or GDNF alone were sufficient to support neuronal survival and morphological complexity, whereas functional maturation, including network activity, required CNTF. Furthermore, BP supported neuronal development and function comparable to NBM, provided appropriate supplementation. Together, our results show that CNTF in combination with either BDNF or GDNF provides the most effective support for both structural and functional maturation of NGN2-neurons derived from male induced pluripotent stem cells (iPSCs). These findings offer a better understanding of how GF supplementation shapes neuronal development and provide a framework for optimizing human neuron culture conditions in disease modeling and drug discovery. Show less

The present study aims to investigate the impact of stroke history on cognitive function, white matter hyperintensities (WMHs), and circulating brain-derived neurotrophic factor (BDNF) levels in brain lesion patients. In this study, we enrolled 228 individuals exhibiting clinical symptoms of stroke from the Golestan Cohort Study. The participants were categorized into two groups based on their stroke history. Subsequently, 120 patients with a history of stroke and 108 patients without obvious brain lesions were subjected to comparative analysis using magnetic resonance imaging (MRI). Montreal Cognitive Assessment (MoCA) and Fazekas scores were used to evaluate cognitive function and WMH burden, respectively. In addition, circulating BDNF levels were measured using the Human BDNF Elisa kit. Totally, 228 patients were recruited in the study with a mean age of 63.8 years. Stroke was found in 52.6%. MoCA scores and plasma BDNF levels were significantly lower in patients with a history of stroke compared to people without such a history after adjusting for age, sex, education and type of residency (adjusted regression coefficient (RC) (95% CI)=-4.0 (-5.0 to -3.0), -3.2 (-4.2 to -2.2), respectively). In addition, the intensity burden of white matter was higher in the stroke group (adjusted RC (95% CI)=1.2 (0.8 to 1.6). The study suggests that a multi-biomarker approach, encompassing measures such as the MoCA score, Fazekas score, and circulating BDNF levels, can provide valuable insight into the neurological status of post-stroke patients and highlight potential avenues for improving patient outcomes through early detection and intervention strategies. Show less

The prevalence of depression, a common mental disorder in clinical practice, has been continuously increasing in recent years, with its intricate etiology and pathogenesis incompletely understood. MicroRNA (miRNA), a highly conserved and widely distributed genetic regulatory factor in eukaryotic organisms, plays a crucial role in the pathophysiology of depression. miR-132, a miRNA molecule specifically enriched in the central nervous system, has emerged as a significant focus in the study of depression. miR-132 is involved in the pathogenesis by modulating critical processes such as dendritic spine remodeling and synaptic efficacy. Current research confirms that the expression profile of miR-132 in peripheral blood and brain tissue samples from animal models of depression shows significant abnormal fluctuations, and its expression level is dose-dependently associated with disease severity, progression, and treatment response. Therefore, this article focuses on a few key elements, including brain-derived neurotrophic factor, neuroinflammatory cascade reactions, neurogenesis, and plasticity, to comprehensively examine the potential role of miR-132 expression in the onset and progression of depression. This review also aims to provide a theoretical foundation for future in-depth research and clinical applications in the field of depression therapy. Show less

ObjectivesThis study aimed to compare the effects of different exercise interventions on brain-derived neurotrophic factor (BDNF) levels in patients with neurodegenerative diseases and to explore regulatory factors.MethodsSearched PubMed, Scopus, Web of Science Core Collection, CNKI and Cochrane Library databases up to March 15, 2025. Bayesian network meta-analysis was conducted using R software, and meta-regression analyzed the moderating effects of training period and frequency.Results42 randomized controlled trials covering 1482 patients were included. The Surface Under the Cumulative Ranking (SUCRA) indicated that stretching training (SUCRA = 78.92) and high-intensity interval training (SUCRA = 69.73) were ranked higher than other exercise modalities and exhibited more favorable effect on BDNF enhancement, although neither demonstrated statistically significant superiority over the blank control. In contrast, combined training (SUCRA = 35.58), aerobic training (SUCRA = 35.17), and resistance training (SUCRA = 12.98) showed relatively lower potential for BDNF enhancement (blank control SUCRA = 67.62). Meta-regression analysis showed that the effect of combined training was significantly and positively correlated with intervention period ( Show less

Overactive urinary bladder (OAB) negatively impacts quality of life, and stress is known to play a key role in its development. However, the mechanisms linking stress to OAB are not yet fully understood. This study examined how chronic activation of neuroendocrine stress pathways, independently of environmental or psychological stressors, affects bladder function and the control of micturition. Utilizing the central role of brain-derived-neurotrophic factor (BDNF) in orchestrating the neuroendocrine stress response within the paraventricular nucleus of the hypothalamus (PVN), our novel experimental model subjected 10-week-old male Sprague Dawley rats to bilateral PVN injections of AAV2 viral vectors expressing either BDNF or GFP (for control). Urine voiding behavior was assessed in UroVoid metabolic cages over 14 weeks post-injections. Bladder strip myography, assessment of bladder wall mechanics, and histology were also conducted to determine any BDNF-induced differences in bladder contractility, capacity and morphology. Prolonged activation of neuroendocrine stress mechanisms with BDNF overexpression in the PVN significantly reduced intermicturition intervals and voided volumes, lowered bladder capacity, and induced relative bladder wall hypertrophy but had no effect on bladder wall mechanics or detrusor contractility. These results indicate that chronic activation of neuroendocrine stress pathways, even without additional environmental or psychological influences of stress, lead to a significant OAB phenotype and reduced bladder capacity. Show less

Neuroplasticity, the brain's capacity to adapt structurally and functionally in response to experiences, is a key factor in recovery from neurological conditions. Growing interest has focused on physical and emotional interventions as potential modulators of neuroplastic processes. A narrative review was conducted using a structured PubMed search of articles published between January 2018 and March 2023. Studies were included if they examined physical activity, emotional well-being, or cognitive training, with outcomes relevant to neuroplasticity. Publications outside these parameters, non-English studies, and case reports were excluded. Twenty-seven articles met the inclusion criteria. The literature described a range of possible influences. Exercise was frequently linked with markers such as brain-derived neurotrophic factor (BDNF) and synaptic plasticity. Emotional interventions, including stress reduction and mindfulness, were reported to have variable effects on neural adaptation. Cognitive training was discussed in relation to functional recovery in conditions such as stroke and traumatic brain injury (TBI). Findings across studies were heterogeneous, and conclusions were limited by differences in study designs and outcome measures. Current evidence suggests that both physical and emotional interventions may influence neuroplasticity, though results are not uniform. The diversity of methodologies and measured outcomes indicates that more rigorous and standardized research is needed. While the reviewed literature points to potential benefits of physical and emotional interventions in modulating neuroplasticity, evidence remains preliminary. Further high-quality longitudinal studies are required to clarify their role in neurological rehabilitation and clinical care. Show less

This study aimed to investigate the effects of perioperative esketamine on postoperative depression and pain in patients undergoing laparoscopic total hysterectomy. 135 patients undegoing laparoscopic total hysterectomy were recruited and randomly allocated to three groups. Finally, a total of 127 patients were selected into the statistical analysis, with the final grouping information as follows: sufentanil group (S1, n = 44), sufentanil combined with 0.25 mg/kg esketamine group (SK1, n = 42) and sufentanil combined with 0.5 mg/kg esketamine group (SK2,n = 41) intraoperatively, then postoperative analgesia was maintained with sufentanil (2 µg/kg) via patient-controlled intravenous analgesia (PCIA) in all groups, while a 1 mg/kg dose of esketamine was added to the PCIA regimen for patients in groups SK1 and SK2. The peripheral blood serum brain-derived neurotrophic factor (BDNF) level, 5-hydroxytryptamine (5-HT) level, Hamilton Depression Scale (HAM-D) scores, visual analogue scale(VAS) scores and the number of PCIA button pressed times in perioperative period were collected. Meanwhile, the postoperative adverse effects including nausea, vomiting, dizziness, respiratory depression and hallucinations were collected and compared between the three groups. Relative to preoperative baseline levels, BDNF and 5-HT levels decreased at the 1th day(1d) post surgery in all groups(P < 0.05), and then followed by a gradual increase thereafter. Compared with S1 group, the SK1 and SK2 group showed significantly higher serum BDNF and 5-HT levels at 1d, 2d and 5d after operation (P < 0.05), and revealed even higher at 1d and 2d after operation in SK2 group(P < 0.05). The HAM-D scores at 1d, 2d and 5d post operation were significantly reduced in SK1 and SK2 group (P < 0.05) compared to S1 group, and decreased even lower at 1d and 2d postoperative in SK2 group(P < 0.05), but no significant difference was found among three groups at 1d before and the 7d after operation. Simultaneously, the VAS scores decreased significantly in SK1 and SK2 group at the 1th hour(1 h), 6 h, 12 h, 24 h, and 48 h after surgery (P < 0.05), and the PCIA button pressed times were also significantly reduced in SK1 and SK2 group (P < 0.05) during the postoperative 48 h. Furthermore, the SK1 and SK2 group showed the lower dosage of remifentanil during the surgery(P < 0.05). However, the postoperative adverse effects had no statistical differences among the three groups. The combined intraoperative and postoperative administration of esketamine was effective in alleviating postoperative depression and pain, without increasing adverse effects in patients undergoing laparoscopic total hysterectomy. Moreover, the 0.5 mg/kg dosage intraoperatively may have the better alleviation property of depression-related indicators. The study was registered with the Chinese Clinical Trial Registry at www.chictr.org.cn (registration date: October 31, 2022; registration number: ChiCTR2200065198). Show less

Impaired cerebral glucose metabolism is a hallmark of Alzheimer's disease (AD). Lactate is an alternative brain fuel; however, whole-body lactate metabolism has not been measured in AD. The Lactate for Energy and Neurocognition Trial (NCT05207397) was a single-arm trial that enrolled 24 cognitively healthy (CH) older adults and 12 cognitively impaired (CI) participants. Subjects underwent a stable isotope lactate infusion to evaluate lactate metabolism, cognitive testing, and blood biomarker analyses. pTau217, brain-derived tau (BD-tau), pTau181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total tau, and brain-derived neurotrophic factor (BDNF) were analyzed by Simoa HD-X (Quanterix). Lactate metabolic clearance rate did not differ between CH and CI subjects (p = 0.988). After infusion, global cognition was improved (p < 0.001) and plasma pTau217 (-33.8%, p < 0.001), BD-tau (-32.6%, p < 0.001), pTau181 (-21.4%, p < 0.001), GFAP (-39.7%, p < 0.001), and NfL (-19.5%, p < 0.001) were reduced. Lactate turnover was not different between diagnosis groups. Lactate infusion improved cognition and reduced AD fluid biomarkers. Individuals with Alzheimer's disease (AD) can metabolize lactate as well as healthy controls. Lactate infusion might improve global cognition and processing speed. Lactate infusion results in significant decrease of AD fluid biomarkers. Show less

This study investigated whether employment status moderates associations between baseline serum biomarkers and antidepressant remission at 12 weeks and 12 months. A prospective cohort of 1086 outpatients diagnosed with depressive disorders received stepwise antidepressant therapy using a naturalistic, flexible treatment protocol. Fourteen serum biomarkers covering immune (hsCRP, TNF-α, IL-1β, IL-6, IL-4, IL-10), metabolic (leptin, ghrelin, total cholesterol), neuroplastic (BDNF), neurotransmitter (serotonin), endocrine (cortisol), and nutritional (folate, homocysteine) domains were analyzed at baseline. Employment-dependent biomarker associations with remission (Hamilton Depression Rating Scale ≤7) at 12 weeks and 12 months were evaluated using logistic regression with biomarker-by-employment interactions and stratified analyses, adjusting for relevant covariates. Higher serotonin levels significantly predicted 12-week remission exclusively among employed patients, with a significant employment interaction. At 12 months, lower leptin levels predicted remission specifically in employed patients, whereas lower TNF-α and higher BDNF levels predicted remission only in unemployed patients, each demonstrating significant employment interactions. Baseline serum biomarkers showed employment-dependent associations with antidepressant remission outcomes, highlighting serotonin's short-term relevance and leptin, TNF-α, and BDNF as longer-term indicators. Although exploratory, these findings suggest that integrating employment status with biomarker profiles may enhance clinical decision-making by identifying patients who are more or less likely to benefit from treatment across different phases of recovery. Replication in independent cohorts is needed to establish the clinical applicability of such employment-tailored, biomarker-informed strategies. Show less

Cognitive impairment is acknowledged as an early stage between normal aging and Alzheimer's disease, emphasizing the need for prompt intervention. There is growing evidence that the gut-brain axis plays a role in regulating cognitive function, indicating that probiotics and their derivatives may impact cognitive functions through the brain-gut axis. In this study, we isolated and identified a novel bacterial strain Show less

The increasing global aging population presents significant challenges related to cognitive decline, mental health disorders, and social isolation. Martial arts exercise emerges as a multifaceted intervention promoting mental health and cognitive vitality among older adults by integrating physical activity, cognitive engagement, and social interaction. This review synthesizes evidence on the neural mechanisms underlying the benefits of martial arts, highlighting their role in enhancing brain-derived neurotrophic factor (BDNF) expression, neuroplasticity, and neural connectivity, which support improved executive functions, memory, and emotional regulation. Both hard martial arts and soft practices, such as Tai Chi, offer distinct advantages in addressing age-related cognitive and psychosocial challenges. Additionally, martial arts foster strong social support systems, reducing loneliness and enhancing emotional resilience through community engagement and shared achievement. Physical and functional benefits, including improved strength, balance, and cardiovascular health, further contribute to overall well-being. Despite promising results, current studies are limited by heterogeneity in martial arts styles, short intervention durations, and variable methodologies. Future research should focus on long-term, standardized interventions employing advanced neuroimaging and biomarker assessments to better elucidate mechanisms and optimize training protocols. Integrating martial arts into health promotion strategies holds substantial potential for enhancing mental health, cognitive resilience, and quality of life in aging populations. Show less

Inflammatory bowel disease (IBD) is a chronic, immune-mediated intestinal disorder driven by dysregulated immune responses in genetically susceptible individuals. Despite recent advances in treatment, more than 30% of patients either fail to respond initially or lose response over time, underscoring the need for a deeper mechanistic understanding of immunogenetic pathways and the development of individualized therapeutic strategies. We first discuss how newly identified susceptibility genes (e.g., IL23R, NOD2, BDNF, SLC) and their polymorphisms influence immune cell function and epithelial barrier integrity. Single-cell technologies have further revealed novel cell subsets and interactions underlying disease heterogeneity. We then explore the clinical efficacy of classical and emerging targeted therapies, including cytokine-specific biologics, JAK inhibitors, and novel strategies aimed at restoring regulatory T-cell function or blocking integrin-mediated lymphocyte trafficking. Additionally, we highlight promising therapeutic approaches such as fecal microbiota transplantation, microbial metabolite-based interventions, and nanotherapeutics. We further discuss how genetic insights and immune biomarkers can facilitate treatment personalization and improve prognostic stratification. Ultimately, this review emphasizes the transition from broad immunosuppression to precision medicine and proposes integrated approaches-combining multiomics profiling, immune monitoring, and novel therapeutics-to achieve sustained remission and improve long-term outcomes in IBD patients. Show less

Low-intensity extracorporeal shockwave therapy (Li-ESWT) is thought to treat erectile dysfunction (ED) by stimulating neovascularization and nerve regeneration as demonstrated in animal models by histologically increased angiogenesis and neuronal-related growth factors, though corresponding human studies are limited. We hypothesized that Li-ESWT results in appreciable increases in growth factors in human tissues, and in this proof-of-concept study we aimed to determine whether markers for neovascularization and nerve regeneration can be detected in the corporal blood of men following Li-ESWT treatment. Patients were prospectively enrolled in a clinical trial of Li-ESWT for ED. Patients received 12 bi-weekly Li-ESWT treatments of 0.2 mJ/mm eNOS, nNOS, VEGF, and BDNF were detectable and demonstrated changes in cavernosal plasma samples following Li-ESWT treatment. Twenty-five patients completed all five study visits. Mean patient age was 63. Mean baseline International Index of Erectile Function-Erectile Function score prior to treatment was 14.24 (±1.21). Corporal plasma samples were analyzed for eNOS, nNOS, VEGF, and BDNF using the enzyme-linked immunosorbent assay. Levels of eNOS, nNOS, and VEGF showed an upward trend following treatment but did not reach significance. BDNF levels were noted to decrease. Corporal blood aspirates may function as surrogates for histological studies to understand effects of Li-ESWT at the tissue level in humans. To our knowledge, this is first the molecular study in human tissues to attempt to quantify neurogenesis and neovascularization in penile tissue following Li-ESWT for ED. Although our sample size is small, we believe this represents a promising first step in understanding the effect of Li-ESWT at a tissue level in men. The clinical significance of our findings is currently unknown, but markers of neovascularization and neurogenesis are detectable in corporal plasma and may change following Li-ESWT. ClinicalTrials.gov Show less

Depression and obesity are amongst the most serious global health challenges. Each of them is associated with high morbidity, chronicity, and socioeconomic burden. Increasing evidence suggests that these conditions are not merely comorbid but share convergent biological pathways (e.g., hypothalamic-pituitary-adrenal axis dysregulation, chronic inflammation, gut dysbiosis, and mitochondrial dysfunction). All these components contribute together to the development and persistence of depressive symptoms as well as to an increase in adiposity. Within this framework, adipose tissue has emerged as an essential endocrine organ that has a deep impact on neuroimmune signalling and mood regulation through its secreted molecules, such as leptin, adiponectin, resistin, omentin, apelin, chemerin, and visfatin. The current management of depression involves a comprehensive, multidisciplinary approach that includes pharmacological treatment and psychotherapeutic support, alongside lifestyle changes. Here we highlight the molecular crosstalk between adipose tissue and the brain, summarising the evidence of adipokines' dysregulation role in connecting metabolic dysfunction to depressive neurobiology. By integrating metabolic, immunological, and neuroendocrine perspectives, this narrative review underscores the need to reconceptualise depression as an immunometabolic disorder. Understanding adipokine-mediated pathways may reveal new biomarkers and therapeutic targets, fostering interdisciplinary approaches. This would allow for the development of new treatment strategies, which include recombinant adipokines, anti-inflammatory agents, and microbial modulation. These new strategies might provide a significant benefit in selected patients, in addition to conventional antidepressants. Show less

Levonorgestrel (LNG), a synthetic progestin widely used in emergency contraception, is increasingly taken frequently and often without medical supervision. With rising concerns that repeated exposure to such hormones may adversely affect brain function, this study investigated whether chronic LNG administration impairs cognitive-like behavior and alters key neurochemical pathways in female Wistar rats. Experimental rats were assigned to three groups receiving normal saline (control) or LNG (4 or 8 µg/kg) every alternate day for 60 days. Cognitive performance was assessed using the Morris water maze (MWM) and novel object recognition (NOR) tests. Hippocampal tissues were subsequently analyzed for glutamatergic markers and downstream signaling molecules involved in learning and memory. Chronic LNG exposure (4 and 8 µg/kg) impaired both spatial and non-spatial memory, evidenced by prolonged escape latency and reduced path efficiency in the MWM, along with a decreased discrimination index in the NOR test. Neurochemically, LNG significantly reduced hippocampal levels of glutamate, N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor ligands, protein kinase A (PKA), calcium/calmodulin-dependent kinase II (CaMKII), and brain-derived neurotrophic factor (BDNF), with the 8 µg/kg dose exerting more pronounced effects. Repeated LNG administration leads to notable cognitive deficits, likely mediated by impairments in glutamatergic signaling and downstream molecular pathways essential for synaptic plasticity. These findings underscore potential neurocognitive risks associated with prolonged LNG exposure. Show less

Boxing, traditionally a competitive sport, is increasingly recognised as a therapeutic exercise modality for women transitioning through perimenopause and menopause a life stage characterised by hormonal changes that can accelerate muscle loss, bone demineralisation, balance impairment, cardiovascular risk, weight gain, and mood fluctuations. Structured, non-contact fitness boxing integrates resistance, impact, and aerobic components, delivering multi-system benefits relevant to this population. Physically, boxing stimulates muscle protein synthesis, preserves lean mass, and provides weight-bearing stimuli to maintain bone density, thereby reducing fracture risk. Dynamic footwork and agility drills challenge proprioception and postural control, improving balance and lowering fall risk. The high-intensity cardiovascular demands enhance heart health, reduce blood pressure, improve lipid profiles, and assist with weight management. Physiologically, boxing's combined strength-endurance format boosts basal metabolic rate, improves insulin sensitivity, and moderates stress hormone levels, supporting metabolic health and resilience to menopause-related changes. Neuromuscular adaptations from complex motor sequences enhance coordination, reaction time, and functional independence. Neurologically, boxing promotes endorphin release and modulates key neurotransmitters such as serotonin and dopamine, improving mood stability and reducing anxiety. Cognitive engagement through learning and executing punch combinations enhances brain-derived neurotrophic factor (BDNF) levels, supporting neuroplasticity, memory, and executive function. Emerging evidence positions non-contact boxing as a safe, engaging, and multi-dimensional exercise strategy for midlife women. It addresses physical, physiological, and neurocognitive domains in one intervention, offering healthcare and wellness professionals a practical, evidence-informed tool to promote strength, stability, cardiovascular fitness, and psychological well-being during the menopausal transition. Show less