Multiple Sclerosis (MS) is a chronic immune-mediated neurodegenerative disorder of the Central Nervous System (CNS) that affects more than 2.8 million people worldwide. It is recognized as one of the leading causes of non-traumatic neurological disability among young adults. It is an inflammatory demyelination disease with axonal damage and progressive neurological disability, which creates high personal, social, and economic costs. The development of neuroimaging, immunobiology, and molecular biology has significantly enhanced the accuracy of diagnosis, disease monitoring, and therapeutic development, enabling earlier intervention and better relapse management with disease-modifying therapeutic agents. These innovations have improved clinical training, retention, and optimization of treatment for relapsing forms of the disease. The Pathophysiology of MS is complex, and the factors that lead to the condition are a complicated interplay of genetic risk, environmental exposure (Epstein-Barr virus, vitamin D deficiency, and smoking), and impaired immunological responses. Despite these gains, there are some significant limitations. There are limited therapeutic interventions that are effective against progressive multiple sclerosis; remyelination failure still plays a role in irreversible disability. Predicting treatment response in this disorder is yet to be identified. The existing literature has identified gaps in understanding immune dysregulation, neurodegeneration, and new modulators, including viral exposures, the gut microbiota, and cell signalling pathways. These unaddressed gaps impede the design of individual and neuroprotective therapeutic approaches that can modify the disease course over the long term. This review critically examines the recent developments and current issues in multiple sclerosis, including etiology and Pathophysiology and diagnostic and therapeutic interventions, with a particular focus on highlighting critical areas of knowledge gaps as well as future research directions that may be used in support of multidisciplinary and integrative approaches to enhance the quality of life and multiple sclerosis clinical outcomes in patients.
INTRODUCTION/OBJECTIVE:Dysfunction of the Neurovascular Unit (NVU) represents a common pathway of injury in ischemia-reperfusion and critical illness. Disruption of blood-brain barrier integrity, microcirculatory reperfusion heterogeneity, and neuroinflammation synergistically amplify secondary neural damage. In this context, attention is increasingly being directed toward interventions that stabilize the NVU as an integrated system rather than targeting neurons alone. This review aimed to summarize and critically appraise the evidence on the beneficial effects of argon in experimental models of ischemia-reperfusion and related critical scenarios, with emphasis on the hierarchy of evidence. METHODS:A focused narrative review was conducted by searching major bibliographic databases through December 2025, followed by manual selection of relevant studies and citation tracking. The SANRA checklist was applied for internal quality control of the narrative review. Statements were structured according to level of evidence ("demonstrated," "indirectly supported," and "not demonstrated") and linked to model type, therapeutic time windows, and outcome measures. A total of 110 references were included. RESULTS:The strongest body of evidence concerns the neuroimmune compartment. Argon attenuates microglial activation and suppresses pro-inflammatory cascades, including inflammasomerelated signaling, thereby reducing pyroptotic markers. In the neuronal compartment, argon is associated with pro-survival shifts, including modulation of the Bcl-2 family balance, reduced caspase-3 activity, and partial preservation of mitochondrial membrane potential. By contrast, microcirculatory improvement is documented mainly at the level of integrated outcomes, such as perfusion, cerebral blood flow, and neurological performance. DISCUSSION:However, the underlying cellular mechanisms involving endothelial cells, pericytes, and microthromboinflammation remain insufficiently characterized. Direct evidence regarding tight junction proteins, matrix metalloproteinases, and endothelial nitric oxide signaling under argon exposure is limited, indicating a clear asymmetry in mechanistic resolution across NVU compartments. CONCLUSION:Current evidence supports argon as a promising NVU-oriented neuroprotective modulator, with the strongest support for neuroimmune mechanisms. Evidence for barrierrelated and microcirculatory mechanisms remains limited and requires direct validation in future studies.
Introduction:: Alzheimer's Disease (AD) is a progressive neurological disorder characterized by unusual behavior, memory deterioration, and a decline in cognitive abilities. A growing body of research indicates that circadian rhythm disturbances play a crucial role in the pathophysiology of AD, impacting both molecular processes and clinical outcomes. This review critically evaluates the molecular interplay between circadian rhythm disruption and AD pathology, explores its impact on clinical manifestations and disease progression, and assesses emerging diagnostic and therapeutic strategies to restore circadian regulation and improve patient outcomes. Methods:: A thorough analysis of recent research on molecular clock genes (CLOCK, BMAL1, PER, and CRY) and their roles in regulating hormone rhythms, metabolism, and sleep-wake cycles was conducted. Research on technology-based methods, therapeutic treatments, and circadian biomarkers was assessed to determine their applicability in AD. Results:: Circadian gene dysregulation was found to exacerbate tau hyperphosphorylation, amyloid- β accumulation, oxidative stress, and neuroinflammation. Clinically, circadian disruption manifests itself as mood disorders, sleep-wake abnormalities, and accelerated cognitive deterioration. Discussion:: Light therapy, melatonin supplements, chrono-pharmacology, and behavioural techniques are among the interventions that have shown promise in restoring rhythm stability. Wearables, smart lighting, neuromodulation, and multi-omics modelling are examples of technological advancements that increase the range of diagnostic and treatment possibilities. Conclusion:: Patient heterogeneity, translational gaps, and a lack of mechanistic knowledge continue to pose difficulties despite progress. To enhance AD outcomes, future research should focus on integrated, customized therapies that target the circadian rhythm.
Background: Stroke is currently the second leading cause of death worldwide, especially among aging populations. Frailty and insulin resistance (IR) have both been associated with stroke risk, but their longitudinal relationship and potential mechanistic links remain unclear. Methods: This prospective study assessed 8,582 Chinese adults aged ≥ 50 years in the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. Frailty was assessed using a validated 29-item frailty index (FI), and IR was estimated by the triglyceride-glucose (TyG) index. Incident stroke was identified by self-reported physician diagnosis. Cox proportional hazards models estimated associations of baseline frailty, frailty transitions, and TyG with incident stroke. Mediation analysis explored whether TyG statistically accounted for part of the frailty-stroke association. Exploratory two-sample Mendelian randomization (MR) was further conducted using European-ancestry GWAS datasets. Results: During follow-up, 584 (6.8%) participants developed stroke. Baseline frailty independently predicted stroke (HR 1.94, 95% CI 1.58-2.39). Compared with participants who remained robust, stroke risk was higher among those with worsened frailty (HR 2.56, 95% CI 1.78-3.67), stable frailty (HR 3.42, 95% CI 2.70-4.34), or improved frailty (HR 1.55, 95% CI 1.21-1.98). Higher TyG levels were associated with stroke risk (Q4 vs. Q1: HR 1.97, 95% CI 1.52-2.55). TyG statistically mediated 4.5% of the baseline frailty-stroke association and 3.4% of the association between frailty worsening and stroke. Exploratory MR analyses based on European- ancestry GWAS datasets yielded directionally consistent genetic evidence (pooled IVW OR 1.41, 95% CI 1.13-1.77). Discussion: Frailty was associated with incident stroke both at baseline and through longitudinal transitions, with the highest risks observed among participants with stable or worsening frailty. Participants with improved frailty remained at higher risk than those who remained robust, although their lower risk estimate compared with stable frail participants may suggest partial risk attenuation and requires cautious interpretation. The small mediation proportion by TyG suggests that IR explains only a minor fraction of the frailty-stroke association, with most of the association likely operating through non-TyG pathways. These findings support careful consideration of frailty assessment and metabolic profiling within multidomain stroke prevention strategies for older adults. Conclusion: Frailty, particularly persistent or worsening frailty, was associated with increased stroke risk among middle-aged and older adults. TyG explained only a small fraction of this association, while exploratory MR findings require cautious interpretation. Frailty and metabolic assessment may help identify individuals at elevated cerebrovascular risk.
INTRODUCTION/OBJECTIVE:Parkinson's disease (PD) is a neurodegenerative disease that can cause motor or non-motor symptoms as a result of damage to nerve cells in the brain. Recently, studies on the diagnosis and prediction of this type of disease continue with the application of machine learning (ML) and deep learning (DL) methods to electroencephalogram (EEG) signals. This study proposes a novel diagnostic framework for classifying PD across both ON and OFF medication states, leveraging EEG-based signal analysis and DL architectures. METHODS:In the proposed approach, EEG signals were obtained from 15 patients with PD (ON and OFF medication), with a mean age of 62.60, and 16 healthy controls (HC), with a mean age of 63,50. Data augmentation was achieved by decomposing EEG signals into subbands using Variational Mode Decomposition (VMD) as a signal processing method. Spectrogram images were obtained by applying the Wavelet Coherence (WC) method to these subbands. The obtained images were classified using a 2D convolutional neural network (2D-CNN). RESULTS:Following the classification process, accuracy, sensitivity, specificity, and F1-Score values were obtained and interpreted. In this study, which examined subband performance, the best results were achieved with 99.80% accuracy, 99.79% sensitivity, 99.80% specificity, and 99.79% F1-Score. DISCUSSION:The findings of this study confirm that the proposed approach outperforms similar approaches in the literature. Given the clinical need for reliable, non-invasive methods for diagnosing Parkinson's disease, the success of the developed model represents a significant contribution to the existing literature. CONCLUSION:This study has contributed a high-performance, innovative approach to the existing literature on Parkinson's disease diagnosis. The successful results obtained clearly demonstrate that the model developed can serve as a robust and reliable framework not only for the diagnosis of Parkinson's disease, but also for similar biomedical signal analyses and the investigation of various neurological disorders.
OBJECTIVE:Intracranial Aneurysm (IA) is characterized by vascular wall degeneration driven by Vascular Smooth Muscle Cell (VSMC) phenotypic switching. Circular RNAs (circRNAs) are emerging regulators of vascular biology; however, the role of circ_0008433 in IA remains unclear. This study investigated whether circ_0008433 regulates VSMC phenotypic switching through the RNA-binding protein HuR. METHODS:circ_0008433 and HuR expression were assessed in IA tissues and control arteries. Human brain VSMCs were transfected with circ_0008433 overexpression or knockdown constructs, with or without HuR silencing. RNA immunoprecipitation (RIP) assays were used to evaluate the interaction between circ_0008433 and HuR. Cell proliferation, migration, and phenotypic markers were assessed using the CCK-8 assay, Transwell assay, qRT-PCR, and Western blotting. RESULTS:circ_0008433 and HuR were significantly upregulated in IA tissues and VSMCs. RIP assays confirmed an interaction between circ_0008433 and HuR. circ_0008433 overexpression was associated with increased HuR mRNA and protein expression and promoted VSMC proliferation, migration, and synthetic phenotype switching, as indicated by increased MMP2 and MMP9 and decreased α-SMA and SM22α expression. These effects were abolished by HuR knockdown. DISCUSSION:These findings identify the circ_0008433-HuR axis as a novel regulatory pathway in IA-associated vascular remodeling. The study suggests that circ_0008433 may contribute to aneurysm pathogenesis by promoting VSMC phenotypic switching via HuR-dependent mechanisms, highlighting its potential as a candidate biomarker and therapeutic target for intracranial aneurysm. Further investigation into the precise molecular mechanisms and clinical translation of this axis is warranted. CONCLUSION:circ_0008433 promotes VSMC phenotypic switching and may contribute to IA progression through a HuR-dependent mechanism. These findings provide insight into the molecular mechanisms underlying IA-associated vascular remodeling and identify the circ_0008433-HuR axis as a potential target for further investigation.
Introduction: Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms due to the loss of dopaminergic neurons in the substantia nigra. Most current therapies are symptomatic and do not arrest the disease course. There is growing interest in nutraceuticals that have the potential to modify disease. Epigallocatechin- 3-gallate (EGCG), a major polyphenol in green tea, has been shown to have neuroprotective properties related to the etiology of Parkinson's disease. Methods: The databases PubMed, Scopus, Web of Science, and Google Scholar were systematically searched. To uncover original research papers, reviews, and meta-analyses on EGCG and its activities in PD, the search strategy was developed by combining keywords such as “Parkinson’s disease,” “Epigallocatechin-3-gallate,” “Neuroprotective,” and “Preclinical”. Non-English articles, conference papers, and studies not connected to neuroprotective processes were excluded. Divergent results were attributed to methodological variations or biological variability, and current high-quality studies were prioritized to address inconsistencies. Seminal articles before 2020 were included to provide historical context and basic mechanical principles. Results: Evidence from preclinical models has repeatedly shown neuroprotective effects of EGCG in a number of PD animal models. EGCG decreases oxidative stress by activating antioxidant pathways, reduces neuroinflammation by suppressing pro-inflammatory cytokines, and attenuates apoptosis via modulating mitochondrial and STAT3-related signaling. Moreover, EGCG prevents α-synuclein aggregation, preserves striatal dopamine levels, protects dopaminergic neurons, and enhances motor performance in animal models. Discussion: EGCG’s pleiotropic characteristics permit the simultaneous targeting of many pathological processes involved in the evolution of Parkinson’s disease. It can pass the bloodbrain barrier, making it more therapeutically effective. However, the compounds' low oral bioavailability and rapid metabolism still pose difficulties for clinical translation. Conclusion: The available experimental results indicate that EGCG could be a successful neuroprotective and disease-modifying therapy for PD. More clinical studies and improved delivery systems are needed to confirm its therapeutic potential in humans.
Background:: The effects of Alzheimer's disease (AD) on society are profound. The blood-brain barrier selectively permits the penetration of specific forms of molecules through the blood circulation into the CNS, which can restrict the effectiveness of medications supplied systemically. The therapeutic targets are located in the CNS. However, local administration channels to the CNS are rather intrusive, which can lead to patient discomfort and limit the feasibility of repeated treatments. Methodology:: This article has evaluated treatment methodologies for AD that use nanoparticles to target the brain and the pathological features of the illness. The material that is currently available has been categorized based on the aspect of AD that is discussed: targeted medication and neurodegeneration. Result:: The use of nanoparticles in the targeted delivery of medications intended to alleviate the symptoms of AD or halt the disease's progression has yielded positive results. Because of their multivalence, nanoparticles can target the treatment site, pass through the blood-brain barrier, and be functionalized with various targeting groups. Intravenous administration, rather than more intrusive techniques, has enhanced drug bioavailability in the CNS. Furthermore, the development of vaccinations and medication formulations for intranasal delivery has utilized nanoparticles. Discussion:: This study focused on the advancement of AD treatment. Nanoparticles are designed to enhance drug bioavailability through intravenous and intranasal routes for quicker brain access with fewer side effects. Nanoparticles also aid in targeting disease features like amyloid- beta plaques and tau tangles. While results in animal models are positive, transitioning to human clinical trials requires a more profound understanding of AD mechanisms and biomarker identification. Conclusion:: Research employing animal models suggests that targeted nanoparticles can enhance the effectiveness of AD treatments. A deeper understanding of AD mechanisms will lead to more successful targeted nanoparticle applications.
Introduction: Intracerebral Haemorrhage (ICH) is one of the most deadly forms of stroke, with a high risk of morbidity and fatality. Due to increased anticoagulant use over the past four decades, the global incidence of hemorrhagic stroke has increased. Chronic hypertension and diseases like cerebral amyloid angiopathy are commonly associated with ICH. Methods: PRISMA criteria were adhered to in this review. PubMed, Web of Science, Scopus, and Google Scholar were used to conduct a thorough literature search. Neural networks, artificial intelligence, diagnostics, machine learning, and intracerebral haemorrhage were among the keywords utilized. Only English-language, peer-reviewed studies published after 2018 were included. After title, abstract, and full-text screening, research focused on AI-based ICH diagnosis and treatment was selected, whereas studies unrelated to or subpar were excluded. Results: Studies on AI-assisted diagnosis, machine learning applications, phytocompound-based therapies, and novel therapeutic approaches for intracerebral haemorrhage were compiled. 32 synthetic compounds, due to their multiple modes of action, including lowering Oxidative stress, minimizing swelling, improving hematoma drainage, and preserving the blood-brain barrier, are promising therapeutic agents. Discussion: Prognostic biomarkers, ultra-early hemostatic therapy, perihematomal protection against inflammatory brain injury, minimal invasive surgery, and primary prevention based on disease pathobiology are among the possible applications of ICH therapy. Around the world, traditional plant remedies have been utilized to manage many illnesses. Conclusion: Epidemiology, risk factors, pathogenesis, diagnosis related to machine learning, artificial intelligence, and treatment based on natural remedies and novel approaches for ICH, their modes of action, and the possible advantages.
INTRODUCTION:Chemotherapy-Induced Peripheral Neuropathy (CIPN), which is caused by oxidative stress, mitochondrial dysfunction, axonal degeneration, and cytoskeletal instability, is a significant dose-limiting hazard of anticancer treatment. Although Convolvulus pluricaulis Choisy (CP), an ancient Ayurvedic nootropic plant, possesses neuroprotective and antioxidant phytoconstituents, its potential therapeutic application in CIPN remains unknown. This study aims to investigate the neurotherapeutic potential of Convolvulus pluricaulis extract in vincristine-induced neuropathy with emphasis on phytochemical profiling, behavioral outcomes, oxidative stress biomarkers, and neuronal integrity. METHODS:Thin-layer Chromatography (TLC) and in-vitro antioxidant tests (DPPH and H2O2 scavenging) were performed on the CP methanolic extract after it was phytochemically characterized. Thirty male Wistar rats were randomly divided into five experimental groups for the evaluation of neuropathy and treatment effects. Male Wistar rats were used to produce vincristine- induced neuropathy (0.1 mg/kg, i.p). For 28 days, the animals were given CP methanolic extract (100 and 200 mg/kg, p.o.). Thermal hyperalgesia, cold allodynia, motor coordination, and behavioral parameters were evaluated. SOD, NO, and histological changes were examined in sciatic nerve samples. RESULTS:Alkaloids, flavonoids, glycosides, phenolics, and amino acids were found using phytochemical screening. TLC identified four different phytochemical stains. In all DPPH and H2O2 tests, the extract showed potent, dose-dependent antioxidant activity similar to that of ascorbic acid. Significant oxidative stress, motor impairment, cold allodynia, and hyperalgesia were brought on by vincristine. In addition to significantly restoring SOD and lowering NO levels (p < 0.001), CP extract significantly enhanced reaction latency, motor coordination, and cold sensitivity. Histopathology demonstrated improved neuronal architecture and reduction of axonal degeneration, particularly at 200 mg/kg. DISCUSSION:According to the current study, Convolvulus pluricaulis extract, which has long been used as a nervine tonic, provides notable neuroprotection in vincristine-induced neuropathy. Thermal sensitivity, motor function, and cold allodynia were significantly improved, suggesting that CIPN-related behavioral impairments have been successfully reduced. Restoring SOD levels and lowering NO levels, along with the extract's potent antioxidant activity, suggest that oxidative stress mitigation is an important factor. The importance of histological healing in maintaining axonal integrity is further supported. CONCLUSION:Convolvulus pluricaulis extract exhibits potent antioxidant, anti-hyperalgesic, and neuroprotective activity against the vincristine model. Its effects appear to be mediated by free radical scavenging, restoration of endogenous antioxidants, and preservation of neuronal structural integrity. CP may serve as a promising phytotherapeutic candidate for managing chemotherapy- induced neuropathy.
Introduction: Cyclic nucleotides, particularly cyclic adenosine monophosphate (cAMP) as well as cyclic guanosine monophosphate (cGMP), are widely regarded as pivotal second messengers involved in a wide array of physiological processes. These include gene transcription, signal transduction, vascular regulation, neuronal communication, energy homeostasis, cellular proliferation and adhesion. Methods: Relevant studies were retrieved through electronic searches of PubMed, Scopus, Web of Science, and Google Scholar. The search strategy combined terms such as “cAMP”, “cGMP”, or “cyclic nucleotide” with “neuroprotective”, “cardioprotective”, and “cancer”. Results: Recent studies have highlighted the critical role of cyclic nucleotide Phosphodiesterases (PDEs) in modulating these signalling pathways by shaping intracellular signalling microdomains and restricting the diffusion of cAMP and cGMP. Importantly, dysregulation of cyclic nucleotide signalling has been implicated in various pathological conditions. Discussion: The growing body of evidence underscores the significance of these messengers in maintaining normal cellular functions and reveals their involvement in the pathophysiology of diseases such as cardiovascular disorders, neurological diseases, cancers, and bone-related conditions. Targeting components of cyclic nucleotide signalling pathways, particularly PDEs, presents a promising therapeutic strategy. Conclusion: This review discusses the fundamental roles of cAMP and cGMP in cellular signalling, the regulatory functions of PDEs, and explores the potential of cyclic nucleotide signalling as a target for the development of innovative therapeutic interventions.
Introduction: This review aims to summarize the possible action mechanism, research progress, and clinical transformation trend of Neural Stem Cells (NSCs) in treating ischemic stroke based on current evidence. Methods: In this review, PubMed, EMBASE, and Science Direct were systematically searched from inception to 2025 using a combination of subject headings and keywords including “neural stem cells”, “ischemic stroke”, “cerebral infarction”, “mechanism”, “signaling pathway”, and “clinical trial”, with search strategies adapted to each database's specific terminology. The selected literature spans basic and translational research on NSC therapy for ischemic stroke, emphasizing molecular mechanisms. Results: NSC transplantation promotes neural repair through multi-dimensional synergistic mechanisms. Structurally, transplanted NSCs migrate to the infarct area, differentiate into mature neurons and glial cells, and integrate into the host neural network, restoring ultrastructure and the neurovascular unit. Functionally, these changes reduce stroke damage and improve motor and cognitive outcomes, supported by long-term anti-inflammatory, metabolic, and regenerative effects. NSCs secrete trophic factors, such as BDNF and VEGF, that enhance cell survival and repair; recent advances in genetic engineering further enhance their therapeutic efficacy. Discussion: Early clinical studies confirm NSC therapy safety and show functional recovery. However, significant challenges remain. These include tumorigenicity risk, inconsistent efficacy, and lack of cell source standardization. Addressing these gaps is essential for clinical translation. Conclusion: NSC therapy offers promise for ischemic stroke treatment. Future research must ensure safety, establish standardized protocols, and elucidate mechanisms to facilitate precise clinical application.
Introduction: Cardiovascular diseases (CVDs) continue to be a leading cause of global mortality, with the contribution of inflammation and immune dysregulation recognized as central drivers in the pathogenesis. While traditional risk factors, such as hypertension, diabetes, obesity, and smoking, contribute significantly, recent evidence suggests that chronic inflammation and immune activation are key mechanisms contributing to atherosclerosis, heart failure, arrhythmias, and myocardial infarction. This review broadly assesses the inflammatory and immunological pathways, highlighting the cellular contributors, molecular mediators, and pathogenic cascades that are involved in the onset and progression of CVDs. The objective of the review is to explain the immune-inflammatory basis of CVDs and critically examine current and emerging therapeutic interventions targeting the aforementioned pathways. Using a strategic narrative review approach, recent clinical trials, preclinical studies, and relevant evidence have been analysed to present a detailed understanding of immune cell contribution, cytokine signaling, plaque formation, and endothelial dysfunction. Methodology: The present review was an organized examination of the existing literature related to the role of inflammation and immunomodulation and their respective therapeutic agents in cardiovascular diseases. This involved searching databases, including PubMed, Google Scholar, ScienceDirect, Elsevier, Bentham Science, and NIH and WHO resources, to identify pertinent articles. Results: Key findings indicate that proinflammatory cytokines like TNF-α, IL-6, and IL-1β, along with chemokines such as MCP-1, contribute to vascular injury, plaque formation, and myocardial remodeling. Immune cells, such as macrophages, dendritic cells, and lymphocytes, facilitate disease progression through cytokine release and maladaptive repair. Anti-inflammatory agents, including colchicine, statins, and targeted monoclonal antibodies (e.g., canakinumab), have shown promise in reducing cardiovascular events, though risks such as bleeding and infection remain. Discussion: The review assessed the interlinked inflammatory and immunological pathways in the pathogenesis of CVDs and identified the cellular and molecular mediators. It also examined current and emerging therapeutic interventions, covering recent clinical and preclinical trials and key findings that clarify immune cell roles, cytokine signalling, plaque formation, and endothelial dysfunction. Conclusion: This review highlights the need for proper immunotherapy in CVDs, supporting targeted modulation of chronic inflammation. Technology and science continue to explore future advancements in personalized medicine and immunomodulation to transform CVD management beyond traditional lipid- and pressure-centered strategies.
Introduction: No studies have examined the interactions among lifestyle, air pollution, and a Polygenic Risk Score (PRS) and the risk of Intracranial Aneurysm (IA). This study aimed to elucidate these associations using data from the UK Biobank cohort study. Materials and Methods: The PRS were classified into three (high, intermediate, and low) genetic risk. The outcome in this study was new-onset IA during the follow-up period. Results: The analysis included 344 incident IA participants [185 (53.78%) <= 60 years, 205 (59.59%) female]. Compared with those having an ideal lifestyle, participants with an intermediate lifestyle (HR: 1.43, 95% CI: 1.12, 1.83; P = 0.004) or poor lifestyle (HR: 1.51, 95% CI: 1.03, 2.19; P = 0.033) had a significantly increased risk of IA. High PRS (HR: 1.79, 95% CI: 1.31, 2.45; P < 0.001) and intermediate PRS (HR: 1.42, 95% CI: 1.07, 1.88; P = 0.014) were associated with a higher risk of incident IA. Apart from the significant associations of PM10 and PMc with IA risk in specific contexts, other air pollution indicators were not associated with increased IA risk. Moreover, no interactions were observed among lifestyle, air pollution, and PRS. Discussion: This cohort study indicates that poor lifestyle and genetic susceptibility were independently associated with higher IA risk, while no association was observed with air pollution. Conclusion: Lifestyle and genetic susceptibility were independently associated with IA risk, while no associations were found with air pollutants.
INTRODUCTION:Alzheimer's disease (AD) is a severe neurodegenerative disorder that progressively worsens with age. Medicinal plants have demonstrated potential for the management of AD. Cassytha filiformis, a native plant of the Indian subcontinent, has been reported to exhibit antioxidant activity, which could be beneficial in neurodegenerative disorders. METHODS:This study evaluates the anti-neurodegenerative effect and possible mechanism of action of a methanolic extract of Cassytha filiformis (MECF). Two compounds, AC-2 and AC-4, were isolated from the extract and assessed for cognitive behavior using the Morris water maze and probe test, followed by evaluation of antioxidant, neurochemical, and anti-inflammatory parameters, as well as in silico studies. RESULTS:Neurochemical abnormalities (acetylcholinesterase (AChE), NMDA (N-methyl-Daspartate), dopamine (DA)), neuro-inflammatory markers (TNF-α, IL-6), and antioxidant parameters (superoxide dismutase (SOD), lipid peroxidation (LPO), nitric oxide (NO)) were evaluated. Histological examination of brain cells assessed the regenerative impact of the isolated compounds. Antioxidant levels and neuroinflammation were significantly reduced (p < 0.05) in the MECF-, AC-2-, and AC-4-treated groups. Additionally, superoxide dismutase and catalase levels were significantly increased in the treated groups. Acetylcholine, NMDA, and dopamine levels showed marked improvement. Histopathological analysis revealed neuroregeneration in the test groups, and hematological evaluations supported these findings by demonstrating normalization of elevated blood profiles observed in the scopolamine-induced groups. DISCUSSION:MECF and its isolated compounds, AC-2 and AC-4, exhibited notable antioxidant and neuro-anti-inflammatory properties, enhancing cognitive function, learning, and memory. The observed neuroprotective effects suggest a potential therapeutic role for these compounds in the management of AD. CONCLUSION:Phenolic compounds present in AC-2 and AC-4 may be integral to the mechanism of action of MECF. Further investigations, including clinical validation, are necessary to explore the therapeutic potential of MECF, AC-2, and AC-4 in AD treatment.
INTRODUCTION:Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, amyloid-beta (Aβ) plaque deposition, tau hyperphosphorylation, oxidative stress, and chronic neuroinflammation. Therapeutic strategies are at present mainly symptomatic and do not modify the course of the disorder. Natural chalcones, precursors of flavonoids, are emerging as multi-target agents for neuroprotection since they have the ability to protect neurons and exert anti-inflammatory and antioxidant activities. METHODS:A systematic literature search was performed in PubMed, Scopus, Web of Science, and Google Scholar utilizing keywords that associate chalcones with Alzheimer's disease. Studies were included if they reported in silico docking, in vitro assays, or mechanistic insights on AD-related targets (AChE, BACE1, GSK-3β, NF-κB). Data extraction included information about the compound's identity, structural changes, docking scores, enzyme inhibition, oxidative stress, and cytokine modulation. The findings were synthesized both qualitatively and quantitatively, with structure-activity relationship (SAR) analysis emphasizing patterns of hydroxylation and methoxylation. These helped in the rational design of chalcone derivatives, which showed potential as multi-target agents against AD pathology. RESULTS:Several chalcones exhibited potent inhibition against AChE and BACE1, besides reducing reactive oxygen species (ROS) generation and preventing the release of pro-inflammatory cytokines. These findings demonstrate their potential to mitigate cholinergic deficits and neuroinflammatory signaling. SAR studies revealed a significant enhancement in bioactivity for certain hydroxylation and methoxylation substituents. This provides insights into the rational design of improved chalcone derivatives. DISCUSSION:Chalcones display multifunctional properties and are able to modulate several AD pathological signatures, suggesting potential application in the prevention of AD symptoms. Their therapeutic importance is emphasized by their combined ability to target cholinergic dysfunction, oxidative stress, and neuroinflammation. The SAR analysis further supports the focused development of chalcone-based derivatives with improved potency. CONCLUSION:The present study provides insights into the mechanistic basis of the neuroprotective activity of chalcones and paves the way for subsequent preclinical evaluation. The chalconebased strategy holds promise for the development of potential drug candidates for the treatment of neurodegenerative diseases such as Alzheimer's disease by addressing the multi-target nature of this complex disease.
INTRODUCTION:Traumatic brain injury (TBI) is a neurological disorder caused by external biomechanical forces such as sports impacts and vehicular accidents. It is a leading cause of morbidity and long-term disability across all age groups. Beyond acute damage, TBI contributes to chronic neurodegenerative processes and persistent neurological sequelae. Growing clinical and experimental evidence suggests that TBI is also associated with systemic alterations affecting the cardiovascular, respiratory, renal, gastrointestinal, and immune systems. METHODS:This narrative integrative review synthesized recent experimental and clinical studies investigating neurological and systemic complications following TBI. Sources were evaluated for evidence related to neurodegenerative cascades, organ dysfunction, and immune-mediated mechanisms. Findings from animal models and human studies were interpreted contextually to highlight mechanistic insights and clinical relevance. RESULTS:The reviewed literature indicates that TBI is associated with both acute and chronic neurological impairment, while also affecting peripheral organ systems. Reported alterations include cardiovascular instability, pulmonary dysfunction, renal hypoperfusion, gastrointestinal barrier disruption, hepatic cytotoxicity, and immune dysregulation. Several studies suggest that peripheral immune activation may contribute to secondary neuroinflammatory processes and unfavorable neurological outcomes. DISCUSSION:The bidirectional interactions between the injured brain and peripheral organs represent a critical but incompletely understood aspect of TBI pathology. Systemic complications may amplify neuroinflammatory cascades and are increasingly recognized as contributors to progressive neurological decline. Integrating brain-systemic perspectives is essential to better understand the multisystem consequences of TBI. CONCLUSION:TBI is increasingly recognized as a multisystem condition that extends beyond the central nervous system. Improved understanding of brain-systemic interactions may inform the development of therapeutic strategies targeting both neurological injury and associated systemic complications, with the potential to reduce morbidity and mortality following head injury.
BACKGROUND:Chronic stress and anxiety have been linked to detrimental physiological impacts that can diminish quality of life. Herbal formulations are being progressively investigated as alternative therapies. This study assessed the anxiolytic and anti-stress properties of Ezenus, a commercially marketed herbal candy for stress relief. It investigated its impact on certain brain neurotransmitters in an experimental animal model. METHODS:A controlled experimental study was performed utilizing Wistar rats (n = 30), randomly allocated into five groups (n = 6/group): vehicle control, diazepam (2 mg/kg), and three doses of Ezenus (200, 400, and 800 mg/kg). The anxiolytic effect was evaluated by the elevated plus maze, open field test, and rotarod test. The swimming endurance test and the tail suspension test assessed the anti-stress effects. Dopamine and serotonin levels in the brain were measured using High-Performance Liquid Chromatography (HPLC). Data were examined using appropriate statistical procedures, with significance set at p < 0.05, 0.01, and 0.001. RESULTS AND DISCUSSION:Ezenus exhibited dose-dependent anxiolytic-like effects, with the maximum dosage (800 mg/kg) demonstrating behavioral outcomes akin to diazepam in anxietyrelated models. In stress paradigms, groups treated with Ezenus demonstrated notable alterations in behavioral responses compared to stress controls. A neurochemical study demonstrated markedly elevated levels of dopamine and serotonin in Ezenus-treated rats compared with stressed controls. CONCLUSION:The results indicate that Ezenus demonstrates anxiolytic and anti-stress effects in preclinical models, likely mediated by monoaminergic neurotransmitter regulation. Although these findings are favorable, further mechanistic studies and clinical trials are necessary to validate their therapeutic efficacy.
INTRODUCTION:Recent research indicates that ferroptosis plays a role in Ischemic Stroke (IS). This study aims to investigate the causal connections and underlying mechanisms involving Ferroptosis-related genes, Gut Microbiota (GM), and IS using the Mendelian Randomization (MR) approach. METHODS:Both two-sample MR analysis and mediation analysis were employed in this study. Initially, the two-sample MR analysis assessed the causal relationship between Ferroptosis genes and IS. To examine the expression patterns of Ferroptosis genes, the GSE140275 dataset was utilized. The mediation analysis aimed to investigate the effect of Ferroptosis gene expression on GM and IS. RESULTS:Results demonstrated that elevated expression of the TFRC gene was significantly and negatively associated with IS function. The TFRC gene influences the incidence of IS indirectly by modulating Megamonas GM. Our findings were further supported by sensitivity analyses, confirming their strong statistical validity. Additionally, six drugs for the prevention and treatment of IS were identified based on their binding to TFRC, and these molecules exhibited stable binding. DISCUSSION:This study, by integrating multiple databases, employs two-sample Mendelian randomization and mediation analysis to reveal, for the first time, the causal association between the ferroptosis gene TFRC and IS. It was found that high expression of TFRC is a protective factor that improves IS function. CONCLUSION:This study reveals the role of TFRC in the progression of IS by regulating Megamonas GM. Regulating Megamonas may reduce the occurrence of IS.
