Search Results (5,236)

The gut, brain, fat body, and various glands, although rich in “CSPs”, are not involved in chemosensory functions. We propose renaming the “CSPs” to “4CSPs” (4-Cysteine Soluble Proteins) to clarify their role, avoiding confusion with proteins also found in wings, hemolymph, and eggs. This report highlights studies related to insecticide resistance and lipid transport and expands on potential intracellular functions, strongly indicating non-chemosensory features of 4CSPs. Additionally, we show a significant correlation between 4CSPs and mucins, translation initiation factors, and actin complex proteins, reinforcing the proposal to rename “CSPs” and consider developmental pattern, tissue distribution, and intracellular localization. Full article

Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by the progressive loss of specific neuronal cell populations and are associated with protein aggregates. Current therapeutic approaches are still limited due to the complexity and heterogeneity of these diseases, which points toward an urgent need to discover and develop new therapeutic agents. Natural compounds are a promising source of novel bioactive agents targeting multiple mechanisms of action implicated in neurodegeneration. Andrographolide (ANDRO) is a natural compound extracted from Andrographis paniculata, a traditional Chinese herb known for its anti-inflammatory and antioxidant properties, which has emerged as a potential neuroprotective agent due to its ability to cross the blood–brain barrier (BBB). ANDRO can exert neuroprotective effects by modulating numerous transcription factors and signaling pathways across different cell types in the central nervous system (CNS). It has been described that ANDRO reverses cognitive and/or motor impairments in AD and PD study models. However, the cellular and molecular mechanisms behind these protective effects are still being elucidated. In this review, we analyze the most recent findings on ANDRO, a neuroprotective agent with multiple biological targets that could reduce the progression of the most prevalent neurodegenerative diseases, AD and PD. Full article

Brain fatigue is a debilitating condition whose molecular complexity—neurotransmitter imbalance, neuroinflammation, and metabolic failure—has long defied effective intervention. Conventional open-loop neuromodulation offers fixed stimulation, but fatigue fluctuates. Closed-loop neuromodulation, adjusting stimulation in real time, holds real promise. Yet its delivery hinges on a single, unresolved bottleneck: the sensing–decision chain. In this review, we deconstruct closed-loop systems into sensing, decision, and intervention, and argue that the true challenge is not technological but informational—how to integrate fast electrophysiological signals with slow molecular biomarkers (inflammatory cytokines, neurotrophic factors, adenosine) into a unified control framework. We show that a “fast-slow variable” architecture offers a practical path forward: fast signals guide immediate responses, slow variables set baselines and thresholds, and their integration enables predictive, pre-emptive intervention. We also examine the molecular correlates of neuromodulation—synaptic plasticity, anti-inflammatory signaling, and neurotrophic regulation—as the mechanistic foundation for therapeutic effect. Finally, we confront the translational triad of causality, inter-individual variability, and the information–energy–time trade-off. We conclude that realizing effective closed-loop neuromodulation for brain fatigue will require parallel advances in both stimulation hardware—improving spatial targeting, dose precision, and modality versatility—and individualized sensing–decision algorithms capable of reliably translating multi-modal biomarkers into timely, safe interventions. Both areas remain active fronts of development, and neither can be neglected in clinical translation. Full article

Major depressive disorder (MDD) is associated with complex neurobiological alterations in which oxidative stress may play a central role; however, direct evidence linking redox biomarkers to alterations in brain chemistry remains limited. This systematic review aimed to synthesize the available evidence on the relationships between oxidative stress and neuroimaging alterations in individuals with MDD. A search was conducted in PubMed, Scopus, and Web of Science (2016–2026) following the PRISMA guidelines, including human studies assessing oxidative biomarkers (central or peripheral) alongside neuroimaging or neurofunctional measures. Four studies met the inclusion criteria (case–control, cross-sectional, and interventional designs). These studies collectively indicate that antioxidant enzymes, glutathione, and malondialdehyde are associated with altered brain activity and connectivity, prefrontal neurochemical changes, and cognitive performance. Overall, the findings support the existence of associations between redox disruption and central nervous system (CNS) alterations in MDD. However, methodological heterogeneity and the limited number of studies highlight the need for further longitudinal and multimodal research to clarify the directionality and clinical relevance of these findings. Full article

Ischemia–reperfusion injury (IRI) is a common form of tissue injury encountered in myocardial infarction, ischemic stroke, solid-organ transplantation, and complex vascular surgery. Timely restoration of blood flow is essential for salvaging ischemic tissues; however, reperfusion itself can induce sterile inflammation and oxidative stress, further compromising microvascular and organ function. Accumulating evidence indicates that alterations in the local microenvironment associated with innate immune responses contribute to this pathological process, with neutrophils representing among the earliest effector cells recruited to injured tissues. In response to danger signals such as damage-associated molecular patterns, neutrophils can release neutrophil extracellular traps (NETs), extracellular web-like structures composed of decondensed chromatin and granular proteins. Extracellular NETs can injure endothelial and parenchymal cells and provide procoagulant scaffolds that contribute to immunothrombosis and local inflammatory responses. Current evidence is derived predominantly from clinical samples and experimental models across different organs. Owing to organ-specific differences in microvascular architecture, cellular composition, and ischemia–reperfusion conditions, the triggers, relative pathological contributions, and responses to NET-targeted interventions are not uniform across tissues. This review first summarizes the intracellular events preceding NET release, the molecular composition of extracellular NETs, and the mechanisms of NET extrusion. We then provide an organ-based synthesis of the local triggers, major injurious effects, and interventional evidence for NETs in the heart, liver, lung, kidney, brain, intestine, limb, and skin, while discussing recurrent pathological features—including microthrombosis, endothelial or barrier injury, and inflammatory amplification—in the context of organ-specific differences and the limitations of the available evidence. In addition, we evaluate therapeutic strategies involving degradation of extracellular NETs and neutralization of their toxic components, inhibition of NET-associated enzymes and upstream signaling pathways, and spatiotemporally targeted delivery, together with the major barriers to clinical translation. Overall, this review provides an organ-structured synthesis of current evidence linking NETs to IRI and offers a framework for understanding their context-dependent pathological roles and for developing organ- and phase-specific therapeutic strategies. Full article

Orofacial pain is a complex and multifactorial condition that affects quality of life and presents important diagnostic and therapeutic challenges. Advances in neuroimaging techniques have enabled the investigation of nervous system alterations associated with pain perception and modulation. This review synthesizes current evidence on structural, functional, and neurochemical brain alterations identified through magnetic resonance imaging (MRI) in individuals with acute and chronic orofacial pain conditions. A comprehensive literature search of PubMed, Web of Science, and Scopus identified MRI studies (structural, diffusion, functional) in adults with temporomandibular disorders, trigeminal neuralgia, persistent dentoalveolar pain, or experimental pain. The main results demonstrated alterations along peripheral trigeminal pathways, brainstem nuclei, and central pain processing networks. Additionally, it was also possible to verify altered gray- and white matter integrity, causing disrupted connectivity within large-scale networks related to pain modulation and cognitive processing. While acute pain reflects transient activation of these pathways, chronic and neuropathic conditions can involve persistent structural and functional reorganization across sensory, affective, and cognitive networks. These findings support the involvement of distributed neural mechanisms and neuroplastic changes in many chronic orofacial pain conditions, while emphasizing that peripheral, central, psychosocial, and contextual factors may contribute to varying degrees across disorders and individuals. Multimodal MRI may provide a basis for future diagnostic, prognostic, and treatment response biomarkers, although most advanced MRI-derived markers remain investigational. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration and chronic neuroinflammation in the brain and spinal cord, involving complex interactions between neurons and immune cells. Carnosine (β-alanyl-L-histidine) has pathophysiological relevance due to its ability to detoxify reactive carbonyl species, including α,β-unsaturated aldehydes, scavenge free radicals, and chelate zinc, and has also been proposed to function in the central nervous system as a histidine reservoir for histamine synthesis. Here, we investigated the effects of carnosine supplementation on the cerebellar proteome of SOD1^G93A ALS rats using quantitative proteomics. Carnosine treatment extensively remodeled mitochondrial, antioxidant, and synaptic vesicle-trafficking protein networks and increased the abundance of glutamatergic and GABAergic receptor subunits relative to untreated ALS animals, with several of these changes exceeding wild-type levels. Pathway enrichment analyses identified significant up-regulation of Rab-mediated vesicle trafficking, synaptic vesicle cycling, and neurotransmitter transport/secretion pathways, alongside a partial reduction in RNA splicing and proteasomal subunits that were elevated in untreated ALS animals. Cross-comparison with the ALS-associated proteomic signature revealed that most carnosine-responsive proteins followed, rather than reversed, the direction of disease-associated change, indicating that carnosine predominantly potentiates an endogenous compensatory program rather than restoring a wild-type-like proteome. Collectively, these findings show that carnosine drives systems-level remodeling of mitochondrial and synaptic networks in the ALS cerebellum, identifying candidate compensatory pathways and supporting further functional validation of carnosine as a component of multimodal therapeutic strategies in ALS. Full article

Nanomaterials are increasingly expected to do more than transport a payload, yet added complexity is useful only when it resolves a rate-limiting diagnostic, transport, release, or monitoring problem. This review develops a function-first framework for precision diagnostics and drug delivery in which formation and processing are linked to nanoscale structure, material properties, demonstrated function, route-specific evidence, and translational value. The scope includes AI-assisted plasmonic and terahertz biosensing; biopolymer nanoparticles and hydrogel depots; barrier-directed nose-to-brain and systemic delivery; graphene and carbon nanotube interfaces; lipid nanoparticles for nucleic acid packaging and endosomal escape; nanoporous, magnetic, and plasmonic carriers; and closed-loop theranostic systems. A platform is treated as genuinely multifunctional only when at least two deliberately engineered functions are experimentally supported and either act on distinct rate-limiting steps or close a sensing–intervention–monitoring loop. This review therefore distinguishes total loading from bioavailable payload, cellular uptake from productive delivery, imaging labels from intact carrier fate, and nominal stimulus responsiveness from controlled release in response to a physiologically realistic trigger. Recent independent studies are used to broaden comparisons across material classes and to separate proof-of-concept performance from translational evidence. Artificial intelligence is considered in three distinct roles—sensor interpretation, formulation/material optimization, and prediction of in vivo behavior—with external validation and, where a model is intended to guide decisions, prospective testing treated as essential. The resulting framework emphasizes biological identity, route-specific safety, carrier-versus-payload tracking, critical quality attributes, manufacturing reproducibility, and a minimum-evidence roadmap from concept to product. Full article

Introduction: Caffeine is a widely consumed psychoactive compound whose central pharmacological effects are mediated primarily through antagonism of adenosine receptors. Wakeful EEG provides a temporally sensitive method for examining caffeine-related changes in oscillatory activity and vigilance-related brain states. This systematic review synthesized evidence concerning the effects of acute and habitual caffeine exposure on non-ERP EEG measures during wakefulness. Materials and Methods: The review followed PRISMA 2020 guidelines. PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 30 May 2026. Eligible studies included human participants exposed to caffeine, coffee, or caffeine-containing interventions and reported EEG outcomes during wakeful resting-state or task-related conditions. Risk of bias was assessed using RoB 2 for randomized trials and ROBINS-I for non-randomized studies. Findings were synthesized narratively because of substantial methodological heterogeneity. Results: Forty-eight studies were included. Resting-state spectral EEG was the dominant paradigm, although studies also examined task-related activity, prolonged wakefulness, sleep deprivation, withdrawal, driving-related drowsiness, coherence, nonlinear complexity, EEG microstates, and multimodal EEG–fMRI measures. Reductions in alpha power or amplitude were among the more frequently reported findings following acute caffeine administration, while attenuation of theta, delta, or other slow-frequency activity was particularly evident under conditions of sleep pressure, prolonged wakefulness, withdrawal, fatigue, or reduced vigilance. However, neither effect was universal. Beta findings were heterogeneous, and changes in alpha frequency, total EEG power, coherence, asymmetry, complexity, and microstates were less consistently examined. The direction and magnitude of EEG responses varied according to caffeine dose, habitual intake and withdrawal status, baseline vigilance, eye condition, task demands, participant characteristics, scalp region, frequency-band definition, and EEG methodology. Evidence concerning coherence, asymmetry, nonlinear complexity, microstates, and multimodal EEG–fMRI outcomes was preliminary. Conclusions: The available evidence does not establish a single reproducible EEG signature or validated electrophysiological biomarker of caffeine response. Reductions in alpha power and attenuation of slow-frequency activity during states of elevated sleep pressure or caffeine withdrawal were among the more frequently reported findings, but substantial methodological and state-dependent heterogeneity limits their specificity and generalizability. EEG changes should also not be interpreted as direct indicators of improved cognitive performance, because electrophysiological and behavioral effects were not consistently concordant across studies. Full article

While genetic alterations in meningiomas have long been the subject of research, the diagnostic and prognostic significance of epigenetic alterations in this most common type of human brain tumor has become increasingly evident in recent years. The most significant findings to date have been DNA methylation analyses and the resulting classification of meningiomas into statistical clusters with different prognoses and various prevailing molecular and phenotypic characteristics. Even the loss of trimethylation of lysine at position 27 in histone 3 (H3K27me3) is of major importance, as it is significantly associated with more aggressive tumor behavior and a poorer prognosis. Since there are far more than just these epigenetic aspects associated with meningiomas, and given the clinical significance of this tumor type, a comprehensive review is needed that reflects the current state of knowledge. We conducted a systematic literature search in PubMed using broad search terms covering all epigenetic modifications and all subcategories. The search was not limited to a specific time frame. The 513 references identified in this manner were fully analysed. To ensure a comprehensive review that covered all relevant topics and reflected the current state of knowledge, 196 references were included in the reference section. In addition to DNA methylation and forms of histone modification, the review includes known alterations in chromatin remodeling complexes, as well as alterations in various types of non-coding RNAs, such as microRNAs and circular RNAs. Moreover, the discussion also addresses epigenetic modifications relevant to oncology that have not yet been identified or investigated in meningiomas. Therefore, this review additionally provides an appropriate overview of epigenetic mechanisms and alterations in general. The broad spectrum of epigenetic alterations opens up far-reaching prospects for future forms of molecular therapy in patients with meningiomas; the current state of epigenetic molecular therapeutic approaches for meningiomas will be addressed in the final section of the discussion. Full article

Background/Objectives: Neonates with hypoxic–ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) frequently develop coagulation abnormalities and bleeding complications, yet data on transfusion burden and its clinical correlates in this population remain limited. Materials and Methods: We performed a secondary analysis of a retrospective single-center cohort of neonates with HIE treated with TH between 2014 and 2022. Transfusion burden was defined as receipt of at least one blood component and coagulation/plasma products during hospitalization and the total number of transfusion episodes. Demographic, perinatal, biochemical, and clinical severity variables were collected. Univariable and multivariable logistic regression analyses were used to identify factors independently associated with transfusion exposure. Brain magnetic resonance imaging (MRI) findings were compared between transfused and non-transfused infants. Results: Among 142 included neonates, 74 (52.1%) received at least one blood product. The median number of transfusion episodes among transfused infants was 2 (IQR 1–3). Fresh frozen plasma and prothrombin complex concentrate were the most frequently administered products. Transfused infants showed higher markers of illness severity. In multivariable analysis, clinically visible bleeding (adjusted odds ratio [aOR] 12.95, 95% CI 1.34–124.97) and need for respiratory support (aOR 2.98, 95% CI 1.19–7.45) remained independently associated with transfusion exposure. Pathological brain MRI findings, including intracranial bleeding and hypoxic–ischemic injury, were more frequent among transfused infants. Conclusions: blood components and coagulation/plasma-derived products transfusions are common in neonates with HIE undergoing TH and appear to primarily reflect underlying disease severity. These findings highlight the need for optimized, evidence-based transfusion strategies in this vulnerable population. Full article

The development of depression frequently impacts epileptic patients due to unmanaged central nervous system changes. This may severely reduce their quality of life. These mental conditions can lead to the administration of illicit drugs for self-medication. However, these substances may increase seizure frequency. The combination of this condition may both interacting brain disorders deeply aggravate each other, requiring simultaneous, comprehensive treatment. The aim will be to systematically evaluate the role of phytomedicine in managing comorbid depression and recreational substance use in people with epilepsy. The methods followed the PRISMA guidelines. This systematic review protocol outlines an evaluation of phytomedicine’s role in managing comorbid depression and recreational substance use in epilepsy patients. Data were searched using nine online databases for 2000–2026 primary studies, extracted data, assessed risk of bias, and performed a narrative or meta-analysis synthesis. It is well documented that depression and recreational substance use frequently coexist, with severity influenced by youth, homelessness, unemployment, childhood trauma, and prolonged substance dependence. Several evidence globally consistently demonstrates strong associations between depressive symptoms and heroin, cocaine, benzodiazepine, and alcohol use. The statistical analyses obtained indicate that substance use and depression reinforce each other, highlighting the need for integrated mental health, addiction, and psychosocial interventions to improve clinical outcomes. This highlighted a complex interaction among depression, epilepsy, and substance use. It emphasised an integrated management approach while cautiously evaluating phytomedicine’s efficacy, safety, and drug interactions. Therefore, the use of phytomedicine may complement integrated epilepsy care by addressing depression and substance use, although robust clinical evidence remains essential for validation. Full article

Dementia is one of the leading causes of disability and dependence among older adults and is increasingly encountered in patients undergoing surgery. As populations age and surgical interventions become more common, understanding the perioperative care of patients with pre-existing dementia has become an important clinical priority. Dementia is associated with reduced cognitive reserve, chronic neuroinflammation, synaptic dysfunction, blood–brain barrier impairment, neurotransmitter abnormalities, and cerebrovascular dysregulation, all of which may increase vulnerability to perioperative neurological injury. Surgical trauma and anaesthesia trigger systemic inflammatory, metabolic, and haemodynamic responses that may disrupt cerebral homeostasis and contribute to perioperative neurocognitive disorders, including postoperative delirium and delayed neurocognitive recovery. Postoperative delirium is consistently associated with accelerated cognitive and functional decline and may represent an important link between perioperative stress and adverse long-term outcomes. However, despite strong biological plausibility, current clinical evidence does not establish a direct causal relationship between anaesthesia, surgery, and accelerated dementia progression. Interpretation of the available literature is limited by methodological heterogeneity, residual confounding, and the frequent exclusion of patients with established cognitive impairment. This narrative review summarizes the neurobiological mechanisms underlying increased perioperative vulnerability in dementia, critically examines current evidence regarding the effects of anaesthesia and surgery on long-term cognitive and functional outcomes, and discusses practical strategies to reduce perioperative risk. A better understanding of these complex interactions is essential to optimize perioperative care and preserve cognitive function, functional independence, and quality of life in this highly vulnerable patient population. Full article

Attention-deficit/hyperactivity disorder (ADHD) involves difficulties in sustaining attention and resisting distraction. This has motivated the development of feedback-driven environments for cognitive control training. Integrating electroencephalography (EEG) sensors into Virtual Reality (VR) serious games for cognitive therapy remains relatively underexplored and requires reliable, non-invasive brain–computer interfaces. The existing solutions use multi-channel systems that primarily suffer from requiring complex hardware, while not combining motor imagery (MI) with concentration levels. Therefore, this case study evaluates the feasibility and data quality of a lightweight, cost-effective sensor configuration for real-time control of mental state. A non-invasive, eight-channel OpenBCI Cyton board was integrated with an EEG cap using the international 10–20 placement system, alongside a Meta Quest 2 headset, to capture MI and concentration signals directly from the user’s scalp. Signal acquisition was hindered by high impedance and channel railing, which required conductive gel mitigation, while mechanical tension from the VR headset strap introduced motion artifacts and noise. Nevertheless, under stable signal conditions, the optimized eight-channel sensor setup achieved a subject-specific online classification accuracy of up to 90% using the deep learning model “EEGNet”. The findings demonstrate the technical feasibility of acquiring and classifying EEG activity using a low-cost eight-channel sensor configuration in an interactive VR-BCI Serious Gaming application, provided that skin–electrode impedance and mechanical sensor interferences are managed. The results provide a basis for future investigation of such systems in cognitive-training applications, while further studies, including clinical evaluations, are required to assess their applicability in therapeutic contexts. Full article

Background and Objectives: brain arteriovenous malformations (AVMs) are a leading cause of spontaneous intracranial hemorrhage in children and carry a disproportionately high lifetime hemorrhagic risk. Materials and Methods: We retrospectively analyzed clinical, morphological, and surgical factors associated with functional outcome in 30 consecutive pediatric patients (≤18 years) who underwent microsurgical AVM resection at a single tertiary neurosurgical center between January 2015 and December 2025. Results: Functional status was assessed with the modified Rankin Scale (mRS) at hospital discharge and at 6–9 months of follow-up; the Wilcoxon signed-rank test, Mann–Whitney U test, Fisher’s exact test, Spearman correlation, and univariable logistic regression were used for analysis. Complete resection on early postoperative CT angiography was documented in all 30 patients (100%). The proportion with a favorable outcome (mRS 0–2) improved significantly from 50.0% at discharge to 76.7% at follow-up (p < 0.0001); 80.8% of survivors improved by at least one mRS point, and none deteriorated. In univariable analysis, the variable most strongly associated with poor outcome was intraventricular hemorrhage (IVH; odds ratio [OR] 28.5, 95% CI 2.65–306.6; p = 0.002); the wide confidence interval reflects the small number of events and precludes a precise estimate of effect size. Lower admission Glasgow Coma Scale (GCS) score (p = 0.0006), higher Supplemented Spetzler–Martin (S–M) grade (p = 0.019), and postoperative complications (p = 0.016) were likewise associated with poor outcome. Because these associations are univariable and unadjusted for confounding, they should be regarded as exploratory and hypothesis-generating rather than as independent predictors. All four deaths occurred in malformations in eloquent locations (p = 0.037). Microsurgical resection achieved complete resection on early postoperative CT angiography in all patients; however, functional recovery appeared to be associated primarily with the severity of the initial hemorrhagic insult—particularly IVH—and with lesion complexity rather than with the achievement of angiographic resection alone. Conclusions: Given the small, surgically selected cohort and the limited follow-up, these findings require confirmation in larger multicenter studies. Full article