Search Results (5,022)

Serum S100B has been proposed as a peripheral biomarker associated with neuroinflammatory and astroglial stress-related processes in major depressive disorder (MDD). This study aimed to evaluate serum S100B levels in patients with MDD and suicidal ideation and to investigate whether childhood trauma mediates the relationship between suicide probability and S100B levels. This study included patients with MDD and suicidal ideation (n = 29), patients with MDD without suicidal ideation (n = 30), and healthy controls (n = 29). Serum S100B levels were measured before and after treatment in patients with suicidal ideation. Suicide Probability Scale (SPS), Childhood Trauma Questionnaire (CTQ), and Rosenberg Self-Esteem Scale (RSES) scores were assessed. Group comparisons were performed using Mann–Whitney U and Kruskal–Wallis tests with Dunn–Bonferroni post hoc analysis. Logistic regression and mediation analyses were conducted to examine the relationships among suicide probability, childhood trauma, and S100B levels. Pre-treatment serum S100B levels were significantly higher in patients with MDD and suicidal ideation compared with healthy controls (median 10.95 vs. 8.97 pg/mL, p = 0.001), whereas post-treatment levels did not differ between groups (median 7.84 vs. 8.97 pg/mL, p = 0.323). Within-group analysis demonstrated a significant reduction in S100B levels after treatment (Z = −3.359, p < 0.001). Additional three-group comparison revealed a significant overall difference in S100B levels among the study groups (H = 8.17, p = 0.017). Logistic regression analysis showed that serum S100B levels were independently associated with suicidal ideation (OR = 1.14, 95% CI 1.02–1.27, p = 0.021). Mediation analyses demonstrated a significant indirect effect of suicide probability on S100B levels through childhood trauma (Sobel Z = −2.45, p = 0.014). Serum S100B levels were elevated during the acute phase of MDD with suicidal ideation and decreased following treatment; however, the specificity of this longitudinal change to suicidality could not be determined within the present study design. The relationship between suicide probability and S100B levels appears to be mediated by childhood trauma, suggesting that S100B may reflect trauma-related neurobiological vulnerability rather than a disease-specific biomarker of suicidality. These findings support a potential association between peripheral glial-related biomarkers and stress-responsive neurobiological processes underlying suicidality. Full article

Microplastic pollution has attracted significant attention in recent years due to evidence that these particles can accumulate in organisms’ tissues and organs and induce adverse health effects, with oxidative stress being a key underlying mechanism of toxicity. The present study investigated the effects of polystyrene microplastics (0.1 μm in diameter) administered at a dose of 0.1 mg/day/animal for 4 weeks, followed by a 2-week recovery period without exposure, on oxidative stress markers in the liver, kidney, and spleen and on hematological and blood biochemical parameters in mice. The results showed a statistically significant increase in white blood cell counts, including lymphocytes, granulocytes, and monocytes, at week 5, indicating the development of an inflammatory response. During the last week of the recovery period (week 6), values returned to levels that approached baseline. Changes in lipid peroxidation demonstrated an induction of oxidative stress, accompanied by alterations in glutathione levels and antioxidant enzyme activities, with a tendency toward recovery after cessation of polystyrene microplastic exposure. In conclusion, these findings demonstrated that even short-term exposure to low doses of polystyrene microplastics could trigger oxidative stress and inflammatory responses, highlighting their potential health risks and the need for further investigation into their long-term biological effects. Full article

Sarcopenia, characterized by progressive loss of muscle mass and function, is highly prevalent among patients with heart failure (HF) and contributes to frailty, disability, and poor prognosis. Shared mechanisms—chronic inflammation, neurohormonal dysregulation, mitochondrial dysfunction, inactivity, and inadequate nutrition—promote anabolic resistance and accelerate muscle wasting. This narrative review summarizes current evidence on the interplay between HF and sarcopenia, focusing on practical strategies for integrated management. Exercise training, particularly combined aerobic and resistance programs, improves physical performance and quality of life, while targeted nutritional interventions ensure adequate energy and protein intake and mitigate malnutrition. Emerging evidence supports the synergistic benefit of coupling tailored dietary support with structured rehabilitation. Despite robust data, implementation of person-centered, multidisciplinary care remains limited. Routine screening for sarcopenia and nutritional risk should be embedded in HF pathways to enable early intervention, functional recovery, and improved long-term outcomes. Full article

Background/Objectives: Bipolar disorder affects about 40 million people worldwide, and the greatest burden of the disease is associated with depressive episodes. About 25% of patients experience drug-resistant depression, in which standard treatment turns out to be insufficient, and monotherapy often does not bring full remission. Despite the use of second-generation antipsychotics, the effectiveness of therapy in TRBD remains limited, which necessitates rational polypharmacotherapy and augmentation strategies. The paper discusses the receptor mechanisms of drug combination, current therapeutic regimens and new interventions such as ketamine acting on the glutamate anergic system. The aim was to synthetically compare the efficacy and safety of available augmentation strategies and polypharmacotherapy. Methods: The material consists of published clinical, observational and randomized trials on pharmacotherapy of drug-resistant bipolar depression, including atypical neuroleptics, ketamine, pramipexole, modafinil, lamotrigine, celecoxib and memantine. The authors analyze receptor mechanisms, neurobiological data and clinical trial results, comparing them with current definitions of TRBD according to ISBD and CINP. Biomarker data, such as the Systemic Immune-Inflammation Index, and the results of neuroimaging and metabolomic studies were also used in the work. Results: The analysis showed that atypical neuroleptics showed limited efficacy and high rates of side effects, while ketamine has the fastest and most pronounced antidepressant effect with a low risk of phase change. Pramipexole has shown promise in terms of long-term efficacy, but its use reduces the high risk of induction of mania and impulse control disorders. Celecoxib as an anti-inflammatory therapy significantly increased response and remission rates compared to escitalopram alone, and memantine showed only an early, short-term antidepressant effect. The results highlight that TRBD requires targeted polypharmacotherapy, with the most promising directions being glutamatergic modulation and anti-inflammatory therapies. Conclusions: Drug-resistant bipolar depression requires a departure from classical monotherapy in favor of rational, mechanistically justified polypharmacotherapy, targeting complex monoaminergic, glutamatergic and neuroinflammatory disorders. Available data indicate that ketamine has the greatest clinical potential among the current strategies, characterized by a rapid onset of action and a favorable safety profile compared to atypical neuroleptics or dopamine agonists. Modulation of inflammatory processes with the use of celecoxib also has promising results, which highlights the importance of biomarkers and personalization of therapy. However, further, large, and well-designed studies are needed to unambiguously determine optimal treatment strategies for TRBD and to verify the effectiveness of new pharmacological interventions. Full article

Plastic pollution has emerged as one of the most pervasive environmental challenges, with microplastics (MPs) widely distributed across marine ecosystems worldwide. This study aimed to assess the uptake of MPs by key fish and invertebrate species from different locations in the coastal zone of the Bulgarian Black Sea. Fish were collected during routine monitoring surveys in September–November 2024, while invertebrates were obtained via scuba diving. The presence of MPs in fish stomachs and invertebrate soft tissues, and their polymer composition, shape and size were analyzed using an Agilent 8700 LDIR Chemical Imaging System. Potential biological effects of ingested MPs were evaluated by an integrated Specific Oxidative Stress (SOS) index. The results revealed MP uptake levels comparable to those reported globally. Small-sized particles (<50 µm) with rounded shapes were most abundant across studied taxa. Polymer composition varied considerably depending on species and sampling region, indicating differences in exposure sources and environmental conditions. Oxidative stress levels in both fish and invertebrates showed substantial interspecific variation, and clear differences between the northern and southern region of the Bulgarian Black Sea. Overall, elevated uptake of MPs appears to contribute to oxidative stress in marine organisms, potentially affecting their health status, resilience, and adaptive capacity, as reflected by increased SOS index values. Full article

Recent paradigms in traumatic brain injury have transitioned from focal-lesion models to an emphasis on diffuse axonal injury and white matter disruption as the primary drivers of cognitive morbidity. This selective review frames information processing speed as the functional signature of this connectivity loss. While processing speed is often theorized as a “cognitive bottleneck” that constrains higher-order functions, we identify critical methodological and conceptual pitfalls in the existing literature. Specifically, we argue that current research is frequently confounded by: (1) measurement impurity, where tasks like the SDMT and TMT-B recruit executive and mnemonic variance; (2) circularity, where speed measures are used to predict time-dependent outcomes; and (3) the neglect of speed–accuracy trade-offs, which may mask volitional cautiousness as neurobiological incapacity. To resolve these challenges, we offer evidence-based recommendations for the clinical setting, including the integration of construct-pure chronometric measures and dual-scoring protocols. We conclude that because white matter integrity functions as a rate-limiting substrate, processing speed must be prioritized as a primary target in early neurorehabilitation. By isolating processing speed from focal-driven deficits, clinicians can more accurately map the path from microstructural disruption to functional recovery. Recognizing this infrastructure is essential to understanding the full scope of cognitive consequences. Full article

Background/Objectives: Psychotic relapse affects over 80% of individuals with schizophrenia-spectrum disorders, driving long-term disability and hospitalization. Clinical relapse management relies on symptomatic monitoring without objective neurobiological tools to guide individualized antipsychotic decisions. Methods: This systematic review synthesizes evidence on neurophysiological, blood-based, molecular, neuroimaging, and digital biomarkers for relapse prediction in schizophrenia-spectrum disorders. Results: Following the PRISMA 2020 guidelines, five databases were searched through March 2026 for longitudinal biomarker studies. Quality was assessed using the Newcastle-Ottawa Scale and PROBAST; findings were synthesized narratively due to substantial heterogeneity. From the 6812 citations screened, 21 studies were included across clinical high-risk, first-episode, and established illness populations. Conclusions: Mismatch negativity and P300 event-related potential (P300) showed the most consistent associations with relapse vulnerability, with mismatch negativity demonstrating relative independence from antipsychotic effects. Inflammatory and neuroendocrine markers—interleukin-6, C-reactive protein, and cortisol awakening response—predicted poor treatment response in multiple longitudinal investigations. Peripheral blood gene expression profiling identified TCF4 network dysregulation as a candidate molecular marker of impending relapse. Neuroimaging models did not outperform standard clinical variables. Digital phenotyping showed ecological promise but remains methodologically nascent. No single biomarker achieves sufficient accuracy for clinical implementation. Neurophysiological and inflammatory markers are the most tractable candidates for monitoring protocols. Future research should prioritize multimodal longitudinal designs, external validation, and systematic antipsychotic confounding control. Among the biomarkers reviewed, mismatch negativity and the interleukin-6/cortisol awakening response combination represent the most tractable candidates for pilot clinical implementation, particularly in specialized early psychosis services and antipsychotic dose-reduction research contexts; no biomarker currently achieves sufficient accuracy for routine use in maintenance treatment decisions. Full article

Background: Radio Electric Asymmetric Conveyer (REAC) neurobiological modulation is proposed as an approach designed to interact with endogenous bioelectrical processes involved in cortical regulation. However, its electrophysiological correlates in physiologically preserved neural systems remain insufficiently characterized. The present study explored whether a standardized REAC Brain Wave Optimization Gamma (BWO-G_B) protocol is associated with measurable changes in resting-state EEG activity in healthy adults. Methods: Nine neurologically healthy participants completed a standardized REAC BWO-G_B protocol consisting of 18 sessions administered over six consecutive days. Resting-state EEG recordings were obtained before and after the intervention. Spectral power was analyzed across the 1–100 Hz range. Multivariate organization of cortical activity was explored using Principal Component Analysis (PCA) and Canonical Discriminant Analysis (CDA), with CDA used only as a descriptive visualization of within-dataset multivariate organization. Cross-correlation analysis was applied to evaluate changes in inter-regional temporal synchronization. Individual-level non-parametric testing (Wilcoxon signed-rank test) was conducted only to characterize within-subject directional spectral modulation across the recorded montage. Results: Post-intervention EEG recordings showed a consistent redistribution of spectral power across cortical regions, predominantly within frequencies below approximately 20 Hz. This pattern was observed across subjects at the individual level. Multivariate analysis revealed a dissociation between PCA, which showed partial overlap between conditions, and CDA, which descriptively showed within-dataset separability between baseline and post-intervention cortical states. Cross-correlation analysis indicated a spatially differentiated redistribution of temporal synchronization across cortical regions. At the individual level, descriptive Wilcoxon analyses indicated broadband spectral differences in seven of nine participants (p < 0.05), with consistent directional trends across all subjects; these p-values should not be interpreted as confirmatory statistical evidence. Conclusions: The findings indicate the presence of a reproducible electrophysiological pattern observed after completion of the REAC BWO-G_B protocol in healthy adults. The observed combination of spectral redistribution, descriptive multivariate organization, and changes in temporal synchronization is consistent with a structured post-intervention modification of cortical activity organization within the present dataset. However, given the exploratory design, small sample size, absence of a control condition, and absence of objective vigilance monitoring, these results should be interpreted cautiously and should not be considered as evidence of intervention-specific effects. Further controlled studies are required to determine specificity, underlying mechanisms, and potential functional relevance. Full article

Background and Objectives: Controlled hypotension during functional endoscopic sinus surgery (FESS) improves surgical field visibility but may pose a risk of subclinical cerebral hypoperfusion. Serum S100Β and neuron-specific enolase (NSE) are established biomarkers of glial and neuronal injury and may reflect perioperative neuroprotection associated with different anesthetic regimens. This study evaluated the effect of four anesthetic protocols on perioperative brain biomarker release during FESS. Materials and Methods: In this single-center, randomized, controlled trial, 88 adult patients (ASA I–III) undergoing FESS under moderately controlled hypotension (mean arterial pressure < 55 mmHg) were allocated to one of four groups: propofol–remifentanil, propofol–remifentanil with ketamine–magnesium, sevoflurane–remifentanil, or sevoflurane–remifentanil with ketamine–magnesium. Serum S100Β and NSE concentrations were measured at three timepoints: early intraoperatively, during hypotension, and at the end of surgery. Biomarker data were analyzed using nested ANOVA and linear mixed-effects models adjusted for relevant covariates. Secondary outcomes included recovery characteristics, surgical field quality, bleeding scores, and perioperative hemodynamics. Results: Baseline demographic and perioperative characteristics were comparable across groups. The group receiving sevoflurane–remifentanil combined with ketamine–magnesium showed the lowest S100B levels (p = 0.01 compared to the propofol–remifentanil group; p = 0.04 compared to the sevoflurane–remifentanil group). Additionally, NSE concentrations were markedly lower in both sevoflurane groups (sevoflurane–remifentanil and sevoflurane–remifentanil plus ketamine–magnesium) compared to the propofol–remifentanil group (p = 0.003 and p = 0.007, respectively). No intergroup differences were observed at baseline and surgical field quality, bleeding, and hemodynamic parameters did not differ significantly among groups. Recovery and extubation times were shortest with propofol–remifentanil, whereas ketamine–magnesium prolonged emergence. Conclusions: Anesthetic technique significantly influences perioperative brain biomarker release during FESS. Sevoflurane-based regimens, with or without ketamine–magnesium, demonstrate more favorable neurobiological profiles under controlled hypotension, although propofol-based anesthesia offers faster recovery. Full article

Background: Human dental pulp stem cells (hDPSCs) are a promising source of multipotent mesenchymal stem cells (MSCs) for regenerative neurology because of their inherent neurogenic potential. However, robust and reproducible protocols for driving their terminal neuronal maturation in a fully defined, xeno-free environment are lacking. Methods: hDPSCs were isolated from a donor tooth and characterized for mesenchymal (CD105, CD90, CD73, CD13) and stemness-associated markers (SOX2, Oct3/4 and Nanog). Cells were differentiated in a novel, fully chemically defined medium 1% ITS medium (ITS: Insulin, Transferrin, Selenium) supplemented with glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF). Neuronal commitment and partial maturation were assessed via immunofluorescence, Western blot, and RT-PCR for markers such as NeuN (Neuronal nuclei) and NF-M (Neurofilament medium chain), and functionally by whole-cell patch-clamp electrophysiology. Results: Although undifferentiated hDPSCs expressed neural progenitor markers (βIII-tubulin and Nestin), only GDNF treatment in a chemically defined medium significantly upregulated mature neuronal markers (NeuN and NF-M) and downregulated mesenchymal markers. Importantly, GDNF-treated cells exhibited key functional changes, including hyperpolarized resting membrane potentials, increased membrane capacitance, and elevated input resistance, which are electrophysiological hallmarks of neural precursor or early neuronal maturation, compared to control cells cultured in medium containing fetal bovine serum (FBS). Although action potentials were not elicited, this represents a significant advancement toward achieving a functional neuronal state. Conclusion: This study demonstrates that a fully chemically defined medium enables GDNF to drive hDPSCs beyond the neural progenitor state towards a partially mature neuronal phenotype. This defined medium protocol eliminates serum variability, enhances reproducibility, and provides a critical step towards standardizing hDPSC-derived neuronal cells for disease modeling and cell-based therapy. Full article

This article advances a transdisciplinary framework for planetary health education grounded in multispecies responsibility and Indigenous relational ontologies. Addressing the limitations of anthropocentric environmental paradigms, the paper proposes an expanded Stratified Relational Responsibility Model integrating ethical, ecological, and neurobiological dimensions of human–more-than-human relations. The framework bridges insights from environmental ethics, anthropology, and affective neuroscience to examine how relational awareness, emotional regulation, and embodied cognition shape pro-environmental behavior. Four pedagogical pillars are introduced to support behavioral transformation, emphasizing relational perception, affective attunement, ethical reflexivity, and collective responsibility. The article further discusses implementation challenges within Western educational contexts and highlights the need for culturally responsive adaptation. By situating human agency within multispecies networks, the model contributes to ongoing debates in planetary health and sustainability education, offering a theoretically robust and practically oriented approach to fostering ecological responsibility. Full article

Fructose 1,6-bisphosphatase 2 (FBP2) is a multifunctional protein whose cellular functions depend on its oligomeric state. Forced FBP2 tetramerization has been linked to microtubule disruption and impaired mitochondrial trafficking, accompanied by abnormal mitochondrial morphology. Here, we identify MIC60 (mitofilin), a core element of the mitochondrial contact site and cristae organizing system (MICOS), as a potential mediator of these effects. Using proximity ligation assay, protein crosslinking combined with mass spectrometry, and ultrastructural analysis, we demonstrate that FBP2 is in close proximity to MIC60 under basal conditions and this proximity is reduced upon FBP2 tetramerization or partial FBP2 depletion. Loss of this proximity coincides with marked remodeling of inner-membrane ultrastructure. These findings are consistent with a working model in which dimeric FBP2 contributes to the coordination of microtubule-dependent mitochondrial positioning with MICOS-linked intramitochondrial organization, providing a plausible mechanistic bridge between metabolic cues (AMP/NAD⁺) and mitochondrial structural integrity. Full article

Background/Objectives: Increasing evidence indicates that gliomas co-opt mechanisms of excitatory synaptic transmission and plasticity to support tumor progression, yet these processes remain poorly characterized in lower-grade gliomas (LGGs). Here, we investigated whether genes associated with excitatory synaptic function are linked to patient prognosis in LGG. Methods: A curated panel of 36 synaptic genes was analyzed in LGG using RNA-sequencing and clinical data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets. Results: Among the genes investigated, DLG2, DLG3, and DLG4, which encode the postsynaptic scaffolding proteins PSD-93, SAP-102, and PSD-95, respectively, showed strong associations with patient overall survival (OS). Higher expression of each gene was consistently associated with longer OS across both datasets. Expression of DLG2–DLG4 was higher in oligodendroglioma and IDH-mutant, 1p/19q co-deleted tumors, and lower in astrocytoma and IDH-wild-type tumors. Furthermore, expression of all three genes positively correlated with a broad gene signature associated with a synaptic gene program, including multiple components of glutamatergic signaling and postsynaptic organization. Conclusions: These findings suggest that elevated expression of DLG2–DLG4 is associated with a transcriptional program resembling differentiated neuron-like features and favorable clinical outcome in LGG. Full article

Background/Objectives: Auditory processing disorders (APDs), defined as impaired neural processing of acoustic stimuli despite normal peripheral hearing, often co-occur with neurodevelopmental disorders (NDDs) and may contribute to language, attentional, and learning difficulties. Emerging evidence suggests that shared neurotransmitter systems may represent a common neurobiological substrate underlying these conditions. The aim of this study is to integrate current evidence on glutamatergic, GABAergic, and monoaminergic systems in neurodevelopmental and auditory processing disorders in children and adolescents, and to evaluate the hypothesis that shared neurotransmitter dysregulation may underlie their clinical overlap. Methods: A narrative review of the literature was conducted through electronic searches in PubMed and Embase up to 31 December 2025, using keywords related to neurotransmitters, NDDs and APDs. Results: Available evidence indicates that an imbalance between excitatory glutamatergic and inhibitory GABAergic neurotransmission has been proposed as a central mechanism in NDDs and may also contribute to auditory processing difficulties through altered neural synchrony, sensory gating and temporal auditory coding. Findings collectively suggest the hypothesis of shared neurotransmitter dysregulation across NDDs and APDs. Conclusions: Auditory processing difficulties may represent sensory-level expressions of shared neurochemical vulnerability across neurodevelopmental conditions. Future longitudinal and multimodal studies are needed to clarify causal relationships and to identify clinically useful biomarkers. Full article

Metal–organic frameworks (MOFs) possess unique structural tunability, abundant coordination sites, and outstanding biosafety, rendering them highly advantageous for the development of high-performance magnetic resonance imaging (MRI) contrast agents. In light of the significant advancements in MOF-derived theranostic platforms, a comprehensive overview focusing on their classification and clinically oriented applications is urgently required. This review provides an in-depth examination of various categories of MOF-derived contrast agents, including T1, T2, dual-mode, ratiometric and 19F imaging systems, and analyzes the correlation between structural characteristics and imaging performance. Furthermore, it highlights typical MRI-guided therapeutic applications, such as those related to atherosclerosis, bacterial infections, and cancer immunotherapy. The review systematically addresses existing challenges, including issues related to biodegradability, metabolic behavior, and biosafety. It also summarizes the rational design principles for novel MOF contrast agents, aiming to facilitate their transition from fundamental research to clinical applications. Full article