Current Neuropharmacology最新文献

{"title":"The Hidden Therapeutic Bridge: Exploring Psilocybin's Role in Depression, Inflammation, and Pain - A Narrative Review.","authors":"Mareli Vazquez-Barreto, Mariana Ugarte-Rocha, Abraham Flores Vargas, Yazmín Adriana García Núñez, Dominique Hahn, Ulises Coffeen","doi":"10.2174/011570159X513731260923101459","DOIUrl":"https://doi.org/10.2174/011570159X513731260923101459","url":null,"abstract":"<p><p>Mental disorders are among the leading causes of non-fatal health loss worldwide and are associated with significant individual, social, and economic burdens. On the other hand, neuropathic pain affects approximately 7-8% of the world's adult population and is a leading reason for medical consultations. A bidirectional relationship between depression and pain has been widely documented. Depression is associated with increased pain perception, while chronic pain may predispose or exacerbate depressive symptoms. The complexity of these two pathologies and the limited efficacy of their current treatments call for research into alternative substances with greater therapeutic success. In this sense, psilocybin has aroused interest in Western medicine since it has been found to have great potential in the treatment of disorders such as depression, anxiety, and pain, among others. In this narrative review, a visualization analysis was conducted to assess the current landscape of psilocybin and psilocin research, spanning from its potential for depression treatment to its potential for pain management. Furthermore, the mechanisms of action of these compounds are analyzed, as are their possible implications in the therapeutics of inflammation and pain, including their participation in the default mode network and the fundamental role of the mystical experiences they generate.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Disruption of the Blood-Brain Barrier and Neurovascular Unit by Lead, Manganese, and Cadmium: A WHO-WHY-WHAT-WHEN-WHERE-HOW Structured Review.","authors":"Rafael Lara-Estrada, Mauricio Molina-Gonzalez, Isaac González-Santoyo, Araceli Diaz-Ruiz, Camilo Rios, Megan Horton, Ernesto Roldan-Valadez","doi":"10.2174/011570159X487175260910112046","DOIUrl":"https://doi.org/10.2174/011570159X487175260910112046","url":null,"abstract":"<p><p>Environmental exposure to lead (Pb), manganese (Mn), and cadmium (Cd) damages the Blood-Brain Barrier (BBB) and the Neurovascular Unit (NVU) through a combination of pathways, including endothelial and astrocyte remodeling, transport dysregulation, oxidative and inflammatory signaling, and altered astrocyte-pericyte control of capillary tone. These changes lead to impaired neurovascular coupling and reduced cerebral blood flow. We collated and synthesized mechanistic evidence from experimental and clinical studies conducted over the 30 years from 1995 to 2025, focusing on studies that reported quantitative environmental exposure data and measured neuroimaging correlates of NVU/BBB injury. Cognitive deficits are associated with low-level blood lead levels (<5-10 μg/dL); blood manganese (Mn) levels of 4-15 μg/L are associated with neurodegeneration. Cadmium (Cd) is a cumulative neurotoxicity biomarker linked to cognitive deficits. Hair Mn tracks chronic inhalation exposure more closely than blood Mn does, and the gap between the two measures suggests that cerebral targets receive more manganese than systemic concentrations imply. Neuroimaging corroborates these mechanistic pathways, documenting region-specific cortical and subcortical volume loss, altered brain perfusion, and changes consistent with inflammatory signaling and with endothelial and astrocyte remodeling. Pallidal T1-weighted MRI and Arterial Spin-Labeling (ASL) perfusion MRI both perform well as neuroimaging biomarkers. Multimetal exposure biomarkers are more indicative of the mixture effect than single metal biomarkers. Longitudinal, mechanistic, and quantitative analyses indicate potential to develop interventions in exposed populations.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the Research Landscape and Global Trends: A Bibliometric Analysis of Event-related Potential in Alzheimer's Disease.","authors":"Suxiao Gang, Jian Fu, Boxu Xie, Xiaonan Qin, Kaiyuan Hu, Junli Zhen","doi":"10.2174/011570159X487808261007063913","DOIUrl":"https://doi.org/10.2174/011570159X487808261007063913","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;There is an urgent need for objective biomarkers to facilitate early diagnosis and dynamic monitoring of Alzheimer's Disease (AD). Event-Related Potential (ERP), as a neuroelectrophysiological technique with high temporal resolution, shows great promise in addressing this demand. However, the macro-level developmental trajectory, research status, and frontier directions within this field remain to be systematically elucidated. This study employs bibliometric methods to delineate the development trends, knowledge structures, and research frontiers of ERP applications in AD, thereby offering a novel perspective for early diagnosis, dynamic monitoring, and efficacy assessment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;Publications related to ERP and AD were retrieved and screened from the Web of Science Core Collection. A comprehensive quantitative and visual analysis was conducted using Microsoft Excel, CiteSpace, VOSviewer, and the bibliometrix package in R. The analysis covered publication trends, national/institutional collaboration networks, author co-occurrence, core journals, reference and keyword co-occurrence, and clustering.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The number of annual publications in this field continued to grow. The United States, China, and Italy were the most productive countries, whereas the cooperation network among institutions and authors was decentralized. Keyword clustering identified six major research topics: P300/N200, Mismatch Negativity (MMN), N170, N400, Olfactory Event-Related Potential (OERP), and Electroencephalography (EEG).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;An analysis of the global research landscape reveals that ERP research has developed from an exploratory tool in the field of AD to an active research field of neuroscience. Journal and citation analysis indicate that the field has distinct clinical problem-driven features; keyword cluster analysis revealed six major themes corresponding to classical cognitive assessment, early sensory memory, and social cognition. Thematic analysis revealed that MMN and other ERP components that are sensitive to early abnormalities may become future research hotspots; however, the overall cooperation in this field still shows a certain degree of geographical concentration and institutional dispersion. In the future, it is necessary to build a closer international and interdisciplinary cooperation network, establish a standardized ERP evaluation scheme, and embed it throughout the entire process of early identification, staging, and monitoring of the effect of intervention in AD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This research systematically presents the current state of research, hotspots, and evolutionary trends in ERP in the field of AD. The results suggest that in the future, a closer international and interdisciplinary cooperation network and further prospective clinical validation are needed to clarify the diagnostic performance and practical a","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Clinical Manifestations to Neural Mechanisms: A Systematic Review of Neurobehavioral Consequences of Pregabalin Misuse and Abuse.","authors":"Wenxiu Guo, Weisheng Huang, Ximan Weng, Jiahui Li, Yihan Wang, Youyou Zhang, Shu-Quan Zhao","doi":"10.2174/011570159X512277260929095531","DOIUrl":"https://doi.org/10.2174/011570159X512277260929095531","url":null,"abstract":"<p><strong>Background/objective: </strong>Pregabalin is a γ-aminobutyric acid (GABA) analog. It is prescribed for neuropathic pain, fibromyalgia, anxiety disorders, and seizures. Pregabalin misuse and abuse have increased rapidly worldwide in recent years, raising public concerns owing to its addictive potential and associated neurotoxicity. To systematically characterize the neurobehavioral effects of pregabalin misuse and abuse, recent research was synthesized, and the relevant literature was reviewed to identify key findings, explore limitations, and outline future directions.</p><p><strong>Methods: </strong>This systematic review followed the PRISMA guidelines. PubMed, Embase, Web of Science, CNKI, and Wanfang were searched for literature covering case series, cross-sectional, prospective, and retrospective studies, and animal experiments. The study's focus was to synthesize evidence of the neurobehavioral consequences of pregabalin misuse and abuse, and explore the association between clinical symptoms and neurobiological mechanisms.</p><p><strong>Results: </strong>A total of 23 studies met the inclusion criteria. Acute overdose consistently produced neuroinhibitory symptoms and reward-seeking behaviors. Repeated or chronic exposure was associated with dose-dependent cognitive impairment, psychiatric comorbidity, addiction, and withdrawal syndrome. Preclinical studies revealed dopaminergic dysregulation, oxidative stress, and neuroadaptive remodeling.</p><p><strong>Discussion: </strong>Human evidence consistently links acute overdose to neuroinhibitory symptoms and reward-seeking behaviors, with severity correlating with dose. Preclinical studies provide a plausible mechanistic hypothesis: acute pregabalin exposure may activate mesolimbic dopamine signaling while chronic high-dose exposure is associated with monoamine disruption, oxidative stress, inflammatory activation, and receptor remodeling in animal models. Direct translation of these findings to human pathophysiology warrants further investigation.</p><p><strong>Conclusion: </strong>Pregabalin misuse and abuse is associated with serious neurobehavioral risks, including acute neurotoxicity, chronic cognitive and psychiatric impairment, and addiction risk. However, the evidence base remains limited, and causal inference is constrained by the predominance of observational human studies and the preliminary nature of animal mechanistic data. Further research should refine risk stratification and inform public health strategies for early identification and intervention.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doxepin Attenuates Cognitive and Anxiety-like Behavioral Deficits Induced by Acute Kidney Injury in Rats.","authors":"Sanaa Jaber, Mo'tasem Alsmadi, Karem Alzoubi, Omar Khabour, Rania Harati","doi":"10.2174/011570159X499564261002162821","DOIUrl":"https://doi.org/10.2174/011570159X499564261002162821","url":null,"abstract":"<p><strong>Introduction: </strong>Acute kidney injury (AKI) is a systemic disorder with consequences extending beyond the kidney, including central nervous system dysfunction. Clinical and experimental evidence indicates that AKI is associated with cognitive impairment and neuropsychiatric disturbances. However, effective strategies to prevent or attenuate AKI-associated brain dysfunction are lacking. Doxepin, a tricyclic antidepressant, exhibits neuroprotective properties that may counteract key mechanisms implicated in AKI-induced neural injury.</p><p><strong>Methods: </strong>In this study, acute renal failure (ARF) was used as an experimental model of AKI. ARF was induced in male Wistar rats through glycerol injection. Animals were allocated into four experimental groups: Control, doxepin (DOX), ARF, or ARF-DOX. Doxepin was given orally at a dose of 5 mg/kg once daily over a 12-day period. Renal function was assessed using serum and urinary urea measurements. Anxiety-related behavior was assessed using the open field test and the elevated plus maze, whereas spatial learning and memory were evaluated with the radial arm water maze.</p><p><strong>Results: </strong>Glycerol-induced ARF resulted in significant alterations in urinary parameters, including reduced urinary urea concentration and increased urine output and flow rate, while serum urea levels did not differ significantly among groups. ARF did not impair spatial learning acquisition but significantly disrupted short- and long-term memory retention. In addition, ARF induced specific anxiety-like behavioral alterations, including increased freezing behavior, reduced rearing activity, and decreased open-arm entries in anxiogenic environments. Doxepin treatment significantly attenuated memory impairments and partially normalized anxiety-related behaviors, without improving biochemical markers of renal dysfunction.</p><p><strong>Discussion: </strong>These findings demonstrate that AKI induces selective cognitive and anxiety-like behavioral deficits and support the existence of a kidney-brain axis. Doxepin attenuated AKI-associated neurobehavioral impairments.</p><p><strong>Conclusion: </strong>This study supports the potential repurposing of doxepin, an established clinically used and brain-penetrant drug, as a therapeutic strategy for attenuating AKI-associated neurobehavioral dysfunction.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotransmitter Receptor Interactions Control Astrocyte Ca²⁺ Signal in the Basolateral Amygdala.","authors":"Jacob A Noeker, Rafael Falcón-Moya, Paulo Kofuji, Alfonso Araque","doi":"10.2174/011570159X488197261002152945","DOIUrl":"10.2174/011570159X488197261002152945","url":null,"abstract":"<p><strong>Introduction: </strong>The endocannabinoid (eCB) system plays fundamental roles in both physiological and pathological aspects of brain function. Activation of type 1 cannabinoid (CB1) receptors in astrocytes by eCBs elevates their intracellular calcium through a signaling pathway that involves activation of Gq/11 proteins, phospholipase C, and IP3R2 to mobilize calcium. Hippocampal astrocytes have been proposed to integrate synaptic information through nonlinear interactions between glutamate and acetylcholine in eliciting calcium responses. However, whether similar integrative interactions occur among other neurotransmitter receptors, namely CB1, glutamate, GABA, and dopamine, and in other brain regions remains unknown.</p><p><strong>Methods: </strong>Here, we investigated whether CB1 receptor activation in astrocytes interacts with signaling pathways of other neurotransmitter receptor systems known to be coupled to Gq/11, Gs, and Gi/o proteins. We monitored astrocytic calcium dynamics in the basolateral amygdala (BLA), a region with prominent integrative functions across multiple neurotransmitter systems, in response to independent or simultaneous receptor activation.</p><p><strong>Results: </strong>We found that simultaneous activation of CB1 receptors with glutamate (Glu), dopamine, or GABA receptors elicited calcium signals that were significantly smaller than the linear summation of responses evoked by each receptor alone. This attenuation was observed in both astrocytic arborizations and somas and was independent of the distance of the domain from the soma. In contrast, the simultaneous activation of Glu and GABA receptors produced calcium responses comparable to the linear sum of their individual effects.</p><p><strong>Discussion: </strong>Our results extend the current understanding of endocannabinoid signaling by revealing that astrocytic CB1 receptor activation can dynamically interact with other neurotransmitter system receptors to generate nonlinear astrocyte calcium signaling outcomes in BLA astrocytes. The integrative signaling capabilities of astrocytes may be particularly relevant in the BLA, suggesting that astrocytes participate directly in shaping amygdala circuit function.</p><p><strong>Conclusion: </strong>Together, these findings demonstrate that neurotransmitter-evoked calcium signaling in BLA astrocytes exhibits receptor-specific nonlinear interactions, supporting a role for astrocytes as integrative elements within local neural circuits.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Resting-State EEG Delta-band Activity at Selected Parietal Electrodes and Cognitive Changes Following Transcutaneous Auricular Vagus Nerve Stimulation in Patients with Mild Cognitive Impairment: An Exploratory Analysis.","authors":"Lei Wang, Huan Ouyang, Jinling Zhang, Xian Lu, Shuai Zhang, Yanan Zhao, Yulong Liang, Lixiao Hao, Yu Wang, Peijing Rong","doi":"10.2174/011570159X491394261005071608","DOIUrl":"https://doi.org/10.2174/011570159X491394261005071608","url":null,"abstract":"<p><strong>Introduction: </strong>Transcutaneous auricular Vagus Nerve Stimulation (taVNS) may improve cognition in Mild Cognitive Impairment (MCI), but its electrophysiological correlates remain unclear. We explored whether parietal delta-band changes were associated with cognitive changes following taVNS.</p><p><strong>Methods: </strong>This exploratory secondary analysis included 26 participants with MCI from a randomized, double-blind, sham-controlled trial (taVNS, n = 14; sham, n = 12) who had valid resting-state EEG data at baseline and Week 24. Absolute and relative 1-3 Hz delta power at Pz, P1, P2, and P5 were analyzed using repeated-measures ANOVA and EEG-cognitive correlations with Benjamini-Hochberg FDR correction.</p><p><strong>Results: </strong>Absolute delta power showed significant time effects at all four electrodes after FDR correction (all q = 0.008). Relative delta power at Pz showed an uncorrected group effect (F = 5.007, p = 0.035; q = 0.218). In the taVNS group, MoCA-B improvement was positively associated with relative delta-power changes at P1, P2, and P5 (r = 0.629-0.652, p = 0.012-0.016), whereas AVLTN7 improvement was negatively associated with absolute delta-power changes across Pz, P1, P2, and P5 (coefficients = -0.418 to -0.613, p = 0.020-0.048). Although these correlations did not reach statistical significance after correction for multiple comparisons, they showed a relatively consistent direction across multiple electrodes.</p><p><strong>Discussion: </strong>Relative and absolute delta power may reflect complementary aspects of spectral modulation. The convergent cross-electrode associations provide preliminary EEG evidence linked to cognitive response to taVNS.</p><p><strong>Conclusion: </strong>Parietal delta-band power may represent a candidate electrophysiological marker of cognitive change following taVNS in MCI. These exploratory findings support further validation of predefined EEG biomarkers in larger, prospectively powered studies.</p><p><strong>Clinical trial registration: </strong>http://www.chictr.org.cn (ID: ChiCTR2000038868).</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-linear Age-related Patterns of Sleep Architecture in First-episode Schizophrenia: A Restricted Cubic Spline Analysis.","authors":"Meihong Xiu, Jing Yao, Xiaoni Guan, Xiaoe Lang","doi":"10.2174/011570159X486672260929211238","DOIUrl":"https://doi.org/10.2174/011570159X486672260929211238","url":null,"abstract":"<p><strong>Background: </strong>The dynamic relationship between age and sleep architecture in the early stages of schizophrenia remains poorly characterized. Traditional linear models may fail to capture the complex patterns of sleep stages across different age groups. This study aimed to examine the non-linear associations between age and sleep parameters in First-Episode Schizophrenia (FES) patients.</p><p><strong>Methods: </strong>A total of 109 FES patients were recruited, and the objective sleep parameters were measured using Polysomnography (PSG). The Restricted Cubic Spline (RCS) analysis was employed to investigate the non-linear patterns of sleep stages across the observed age range (14-45 years), controlling for biological sex, Body Mass Index (BMI), and duration of illness.</p><p><strong>Results: </strong>RCS analysis suggested statistically significant non-linear associations between age and selected sleep parameters. Specifically, the relationship between age and percentage of N3 sleep (N3P) demonstrated a U-shaped pattern (pnon-linearity =0.0007), with an estimated nadir at approximately 31.1 years, after which N3P appeared to stabilize or modestly increase. The slope was negative below approximately 31.1 years and positive above this age point. For the percentage of N2 sleep (N2P), the spline curve showed an inverted U-shaped cross-sectional association between age and N2P (pnon-linearity =0.03). N2P was highest among individuals in their early 30s, peaking at an inflection point of 31.3 years and relatively lower among both younger and older FES patients. No significant non-linear relationships were observed for Arousal Time (AT) and percentage of REM (REMP) (all p > 0.05).</p><p><strong>Discussion: </strong>In FES patients, the relationship between age and sleep architecture was characterized by distinct non-linear age-related patterns rather than simple linear associations. The age of approximately 31 years appeared to be a critical inflection point for both N2 and N3 sleep stages in FES patients.</p><p><strong>Conclusion: </strong>These findings provide a more nuanced description of the sleep profile in early-stage SZ.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Differentiation and Apoptosis in Glioblastoma Driven by GQIcombi: Evidence from RNA-seq Analysis.","authors":"Varvara Kolesnikova, Ksenia Rubetskaya, Fatima Dzarieva, Dmitry Usachev, Galina Pavlova","doi":"10.2174/011570159X496967260930230524","DOIUrl":"https://doi.org/10.2174/011570159X496967260930230524","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma is one of the most common and aggressive primary brain tumors in adults, and remains universally incurable. Due to the cellular heterogeneity of glioblastoma, the development of effective therapies remains a pressing and as-yet-unsolved challenge. Transcriptomic profiling provides a powerful approach to delineate molecular perturbations induced by candidate therapeutic compounds.</p><p><strong>Methods: </strong>In the present study, a comprehensive transcriptome analysis of human glioblastoma cells following exposure to GQIcombi, a multifactorial combination with demonstrated antiproliferative and neurodifferentiation-promoting activities previously established in grade 2-4 glioma cell cultures, was performed.</p><p><strong>Results: </strong>Comprehensive pathway targeting creates a synergistic anti-tumor effect, simultaneously disrupting proliferation, survival, and invasion, while inducing programmed cell death.</p><p><strong>Discussion: </strong>The multi-level approach prevents compensatory activation and overcomes inherent treatment resistance in glioblastoma cells.</p><p><strong>Conclusion: </strong>The study's investigation focused on essential signaling pathways that maintain tumor cell homeostasis, thus revealing potential mechanisms underlying GQIcombi's antitumor activity.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role and Mechanisms of Gut Microbiota in the Progression of Hepatic Encephalopathy.","authors":"Yirui Hu, Ting Wei, Shuyan Wang, Ye Yang, Ling Yang, Huikuan Chu","doi":"10.2174/011570159X513988260915065036","DOIUrl":"https://doi.org/10.2174/011570159X513988260915065036","url":null,"abstract":"<p><p>Hepatic encephalopathy (HE) is a severe complication of end-stage liver disease that is associated with high mortality; however, its therapeutic options remain limited. The traditional mechanistic understanding focuses on ammonia neurotoxicity, although intestinal bacteria also play a significant role through the gut-liver-brain axis. This review primarily discusses the characteristics of gut dysbiosis in HE, which is marked by a progressive loss of beneficial commensals (e.g., Lachnospiraceae, Ruminococcaceae, and Faecalibacterium) and an overgrowth of potentially pathogenic bacteria (e.g., Enterobacteriaceae, Streptococcaceae, and Veillonellaceae). Unlike previous reviews which have largely focused on phylum- or genus-level changes, this review provides a species-level synthesis of gut microbial alterations in HE. We further summarise the multifaceted mechanisms by which the gut microbiota contributes to HE pathogenesis, including the impairment of intestinal barrier integrity, activation of systemic and neuroinflammation, alterations in microbial metabolites (such as ammonia, short-chain fatty acids, bile acids, and aromatic amino acids), and disruption of neuroendocrine signalling pathways. Furthermore, herein we summarise the microbiota-targeted intervention measures for HE, including aetiological treatments, drug therapies (lactulose and rifaximin), live microbial therapies (probiotics, prebiotics, synbiotics, faecal microbiota transplantation, etc.), and dietary adjustments. Emerging approaches, such as engineered bacteria and phage therapy, are also discussed, along with the barriers to their clinical translation and safety considerations. In summary, targeting the gut microbiota offers a new approach for the precise treatment of HE, although challenges remain in translating these findings into routine clinical practice.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}