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Search Results (207)

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Keywords = stress behavior recognition

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25 pages, 18533 KB  
Article
Cognitive and Neurochemical Effects of Brivaracetam Co-Administered with Ethanol: A Preclinical Study
by Ewa Zwierzyńska, Joanna Stragierowicz, Marzenna Nasiadek, Michał Klimczak and Bogusława Pietrzak
Int. J. Mol. Sci. 2026, 27(16), 7435; https://doi.org/10.3390/ijms27167435 - 20 Aug 2026
Viewed by 125
Abstract
Ethanol affects the central nervous system, with frequent use leading to memory impairment. This study aims to determine the effects of brivaracetam on ethanol-induced memory impairment and alterations in selected neurotransmitter levels, trace elements in the brain and serum oxidative stress parameters in [...] Read more.
Ethanol affects the central nervous system, with frequent use leading to memory impairment. This study aims to determine the effects of brivaracetam on ethanol-induced memory impairment and alterations in selected neurotransmitter levels, trace elements in the brain and serum oxidative stress parameters in rats. Brivaracetam was administered for three weeks (6 mg/kg b.w.) before behavioral tests. Ethanol was given as a forced model (5 g/kg b.w.). Spatial memory was evaluated with the Morris water maze test and recognition memory with the novel object recognition test. GABA and glutamate concentrations were evaluated in the cerebellum, hippocampus, and cerebral cortex, while superoxide dismutase (SOD) and catalase (CAT) activities and malondialdehyde (MDA) levels were measured in blood serum. The levels of copper, manganese, zinc, iron, and magnesium in the brain were also determined. Brivaracetam was found to negatively affect spatial and retrieval memory when administered with ethanol and during withdrawal; however, the drug improved ethanol-induced short-term recognition memory impairment. Furthermore, brivaracetam increased CAT activity, while MDA was decreased and SOD increased in all drug-treated animals. Brivaracetam may counteract ethanol-induced manganese brain concentration, but increases iron, magnesium, and copper concentrations. Hence, brivaracetam use induces various effects on the central nervous system. Full article
(This article belongs to the Section Molecular Neurobiology)
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13 pages, 566 KB  
Systematic Review
Complex Post-Traumatic Stress Disorder and Borderline Personality Disorder: A Systematic Review of Diagnostic Distinction and Comorbidity
by Alejandra Galvez-Merlin, Sandra Diaz-Gonzalez, Esther Julian-Montaner, Noelia Fuentes-Garcia, Myriam Gonzalez-Gomez, Jose Manuel Lopez-Villatoro, Marina Diaz-Marsa and Jose Luis Carrasco
Healthcare 2026, 14(16), 2527; https://doi.org/10.3390/healthcare14162527 - 13 Aug 2026
Viewed by 445
Abstract
Introduction: The recognition of Complex Post-Traumatic Stress Disorder (CPTSD) as a distinct diagnosis in ICD-11 has intensified the need to clarify its boundaries with Borderline Personality Disorder (BPD), given their symptom overlap and shared traumatic origins. Therefore, this systematic review aimed to examine [...] Read more.
Introduction: The recognition of Complex Post-Traumatic Stress Disorder (CPTSD) as a distinct diagnosis in ICD-11 has intensified the need to clarify its boundaries with Borderline Personality Disorder (BPD), given their symptom overlap and shared traumatic origins. Therefore, this systematic review aimed to examine whether CPTSD is distinct from BPD, assess their comorbidity and symptom overlap, identify key criteria for differential diagnosis, and explore therapeutic implications. Method: A systematic search was conducted in PubMed, Scopus, and Web of Science following PRISMA 2020 guidelines. Seven empirical studies (2015–2025) were included, comprising 2574 adults (mean age 40.4 years; 73.3% women). Methods included latent class analysis, structural equation modeling, and network analysis. The methodological quality of the included studies was evaluated independently by two reviewers using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Results: Findings consistently supported that CPTSD and BPD are empirically distinguishable, though substantially correlated, particularly within the ICD-11 framework. High symptom co-occurrence was observed, with affective dysregulation identified as the symptom most centrally connecting the two symptom networks. Self-concept emerged as the most robust differentiator: stable and persistently negative in CPTSD versus unstable and fragmented in BPD. Shame was a key affective marker of more severe presentations, and trauma severity, rather than diagnostic category, was associated with symptom variation across studies. Conclusions: CPTSD and BPD are distinct yet frequently co-occurring conditions. Differential diagnosis should focus on self-concept stability, patterns of behavioral dysregulation, and shame. Treatment requires individualized, trauma-informed, and shame-sensitive approaches, with transdiagnostic emotion regulation strategies across presentations. These conclusions should be interpreted with caution, given the predominantly cross-sectional design and methodological heterogeneity of the available evidence. Full article
(This article belongs to the Special Issue The Relationship Between Mental Health and Psychological Trauma)
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19 pages, 3010 KB  
Article
Ginsenoside Rh1 Modulates GABAergic Inhibitory Homeostasis and Mitochondrial Quality Control During Lead (Pb)-Associated Neuronal Dysfunction
by Xiang Li, Tingting Wang, Linfeng Mo, Huixin Cao, Zhongting Lv, Jia Yu, Shuang Liu, Yantong Sun and Tianli Chen
Molecules 2026, 31(16), 2801; https://doi.org/10.3390/molecules31162801 - 11 Aug 2026
Viewed by 331
Abstract
Disruption of neuronal excitation–inhibition balance and mitochondrial quality control may contribute importantly to lead (Pb)-induced neurotoxicity, but nutritional modulators targeting these processes remain poorly characterized. This study investigated the protective effects and underlying mechanisms of ginsenoside Rh1, a ginseng-derived bioactive compound, in Pb-exposed [...] Read more.
Disruption of neuronal excitation–inhibition balance and mitochondrial quality control may contribute importantly to lead (Pb)-induced neurotoxicity, but nutritional modulators targeting these processes remain poorly characterized. This study investigated the protective effects and underlying mechanisms of ginsenoside Rh1, a ginseng-derived bioactive compound, in Pb-exposed mice and Pb-treated HT22 hippocampal cells. Chronic Pb exposure caused spatial recognition deficits, reduced exploratory activity, anxiety-like behaviors, and marked neuronal injury, accompanied by Pb accumulation in blood and brain tissues, elevated IL-1β, TNF-α, and IL-6 levels, oxidative stress, reduced Gama-aminobutyric acid (GABA) content, and dysregulated NKCC1/KCC2 expression. In HT22 cells, Pb increased intracellular ROS generation and disrupted mitophagy-related signaling, as indicated by alterations in PINK1, Parkin, LC3, P62, and GABARAP. Rh1 treatment alleviated Pb-induced behavioral abnormalities and neuronal pathology, reduced Pb burden, suppressed neuroinflammatory responses, enhanced antioxidant defenses, improved Pb-associated alterations in GABAergic regulation, and modulated mitochondrial quality-control signaling in vivo and in vitro. These findings suggest that Rh1 may represent a promising nutritional intervention strategy for mitigating Pb-associated neurotoxicity. Full article
(This article belongs to the Section Food Chemistry)
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26 pages, 14481 KB  
Article
Silica-Inspired Aerogel Thermal Metamaterials with Gradient Porosity: High-Temperature-Induced Pore Sintering Evolution via Nanoindentation
by Yiming Song, Mingyang Yang, Shuxu Li, Huiyu Yang, Ying Yin and Mu Du
Gels 2026, 12(8), 684; https://doi.org/10.3390/gels12080684 - 3 Aug 2026
Viewed by 241
Abstract
Localized densification of nanoporous silica under combined mechanical compression and elevated temperature involves coupled pore collapse, skeletal rearrangement, and thermally activated sintering. Clarifying how local pre-compression regulates these processes is important for understanding the surface and near-surface densification of nanoporous silica and related [...] Read more.
Localized densification of nanoporous silica under combined mechanical compression and elevated temperature involves coupled pore collapse, skeletal rearrangement, and thermally activated sintering. Clarifying how local pre-compression regulates these processes is important for understanding the surface and near-surface densification of nanoporous silica and related porous materials. In this study, the microscopic sintering behavior of a silica-inspired aerogel-like nanoporous model under the coupling of non-uniform local stress and high-temperature fields (indentation depths of 50–150 Å and temperatures of 298–1800 K) was systematically investigated using molecular dynamics simulations combined with a three-dimensional (3D) topological recognition algorithm (probe sphere method and DBSCAN clustering). The results indicate that the sintering densification of the silica-inspired aerogel model exhibits significant pore-size dependence and a “depth-temperature inverse relationship”: the local pre-compression induced by the 150 Å indentation facilitates thermally activated atomic rearrangement and shifts the onset of densification to a lower temperature, leading to an early bimodal splitting of the pore size distribution at 1300 K, accompanied by a significant jump in the elastic modulus from 3.0 to 10.07 GPa. In contrast, the 50 Å shallow region requires heating to 1800 K to achieve an equivalent densification effect. Furthermore, topological analysis quantitatively reveals the phase transition process of the pore network from connected to isolated: taking 1300 K as an example, the number of connected pore clusters decreases from the initial 86 to 70 (at 1000 ps), marking the fracture of the connected network; subsequently, the number of isolated pores surges to 4861, and the residual connected framework is severely fragmented into 136 micro-clusters. Based on the above microstructural and topological evolution data, a four-stage thermo-mechanical synergistic evolution process of the silica-inspired aerogel model is summarized. These findings provide quantitative fundamental data that conceptually supports the design of functional gradient structures with alternating “dense-thermally-conductive” and “porous-thermally-insulating” layers within a single continuous aerogel matrix; such structures may be realized in the future through strategies such as arrayed nanoindentation combined with high-temperature sintering. Full article
(This article belongs to the Section Gel Applications)
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43 pages, 9732 KB  
Review
Not All Heroes Wear Capes—Some Just Glow: Exploring Carbon Dots as Nanoagents Against COVID-19
by Alexandra Karagianni, Adamantia Zourou, Aekkachai Tuekprakhon, Nadiya Boyar, Zania Stamataki and Konstantinos V. Kordatos
Processes 2026, 14(14), 2372; https://doi.org/10.3390/pr14142372 - 22 Jul 2026
Viewed by 588
Abstract
The coronavirus disease (COVID-19) pandemic highlighted critical limitations in ongoing diagnostic and therapeutic strategies, underscoring the urgent need for alternative and complementary approaches. Carbon dots (CDs) represent a novel class of fluorescent carbon-based nanomaterials with increased research interest owing to their enhanced biocompatibility, [...] Read more.
The coronavirus disease (COVID-19) pandemic highlighted critical limitations in ongoing diagnostic and therapeutic strategies, underscoring the urgent need for alternative and complementary approaches. Carbon dots (CDs) represent a novel class of fluorescent carbon-based nanomaterials with increased research interest owing to their enhanced biocompatibility, tunable photoluminescence, aqueous solubility, and rich surface chemistry. This review outlines current approaches in the diagnosis and treatment of COVID-19, along with the main structural, physicochemical, and biological features of CDs. Recent advances in the application of CDs as biosensing and antiviral nanomaterials against SARS-CoV-2 are critically discussed with an emphasis on the influence of synthetic routes, precursor compounds, heteroatom doping, surface functionalization, and purification strategies on their optical behavior and biological performance. CD-based biosensors mainly rely on fluorescence-sensing strategies, exploiting changes in photoluminescence intensity or energy-transfer processes upon recognition of viral targets. Electrochemical approaches are also investigated, highlighting the role of CDs as electrode modifiers to enable sensitive immunodetection in complex biological samples. Apart from diagnosis, the therapeutic potential of CDs is underscored by inhibiting viral entry, replication, disrupting cell membranes, or modulating oxidative stress. Finally, current limitations, challenges, and future perspectives regarding mechanistic understanding, synthesis parameters, biodistribution, and clinical translation are discussed, demonstrating the potential of CDs as novel “shiny weapons” against COVID-19, combining therapeutic and diagnostic functions. Full article
(This article belongs to the Section Biological Processes and Systems)
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17 pages, 927 KB  
Article
Evaluation of the Impact of Micellar Formulation of Resveratrol on Neurotrophic Factors and Neuromodulatory Potential in Healthy Rats
by Maria Lazarova, Miroslava Stefanova, Elina Tsvetanova, Almira Georgieva, Krasimira Tasheva, Lyubomira Radeva and Krassimira Yoncheva
Molecules 2026, 31(14), 2536; https://doi.org/10.3390/molecules31142536 - 21 Jul 2026
Viewed by 374
Abstract
Encapsulation of resveratrol (RVT), a natural polyphenol, in mixed Pluronic F127/P123 micelles (mRVT) has enhanced its pharmacological efficacy in experimental dementia models. The aim of this study was to evaluate neurochemical and behavioral parameters of mRVT treatment in healthy subjects. For this purpose, [...] Read more.
Encapsulation of resveratrol (RVT), a natural polyphenol, in mixed Pluronic F127/P123 micelles (mRVT) has enhanced its pharmacological efficacy in experimental dementia models. The aim of this study was to evaluate neurochemical and behavioral parameters of mRVT treatment in healthy subjects. For this purpose, pure RVT and mRVT (both at 10 mg/kg i.p.) were applied for 9 consecutive days in healthy male Wistar rats. Memory performance was assessed using the novel object recognition and passive avoidance tests. Neurotransmitter levels, neurotrophic and transcription factors, and oxidative stress markers were quantified in the cortex and hippocampus using enzyme-linked immunosorbent assay kits. Our results showed that neither treatment altered locomotor activity or short-term memory performance. Both RVT and mRVT treatments reduced hippocampal acetylcholinesterase activity to a similar extent and elevated acetylcholine levels in the cortex and hippocampus, with mRVT producing significantly more pronounced effect in the hippocampus. Compared to pure RVT, mRVT elicited a greater increase in noradrenaline and serotonin levels in both brain regions and comparably upregulated BDNF and pCREB protein levels in the cortex. Furthermore, mRVT uniquely reduced cortical lipid peroxidation—an effect absent with pure RVT treatment. These findings demonstrate that micellar encapsulation substantially amplifies the neurochemical efficacy of resveratrol under physiological conditions without adverse behavioral effects. Full article
(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)
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21 pages, 6509 KB  
Article
Trichoderma asperellum Suppresses Gray Mold Caused by Botrytis cinerea and Enhances Disease Resistance of Blueberry
by Yanxia She, Xiaotong Song, Tingzhen Wang, Yujia Li, Huiyan Zheng, Shuyuan Wang, Yutong Liu, Fei Gao, Xin Lou and Yuejia Dang
J. Fungi 2026, 12(7), 515; https://doi.org/10.3390/jof12070515 - 14 Jul 2026
Viewed by 577
Abstract
With growing global recognition of the nutritional value of blueberries, their cultivation has expanded significantly across various regions. However, gray mold disease, caused by Botrytis cinerea, remains a major challenge in postharvest storage and transportation. In this study, two strains—Trichoderma asperellum [...] Read more.
With growing global recognition of the nutritional value of blueberries, their cultivation has expanded significantly across various regions. However, gray mold disease, caused by Botrytis cinerea, remains a major challenge in postharvest storage and transportation. In this study, two strains—Trichoderma asperellum BBR–A and B. cinerea BC7–1—were isolated and identified from the blueberry rhizosphere and diseased leaves. Co-culture assays demonstrated that BBR–A exhibits potent antagonistic activity, rapidly suppressing the growth of the pathogen BC7–1 through mycoparasitic behaviors, including hyphal coiling, penetration, and degradation. Transcriptomic analysis revealed that upon interaction with BC7–1, BBR–A undergoes extensive reprogramming of carbon metabolism, with coordinated upregulation of genes encoding degradative enzymes, transporters, and stress-related proteins. Congo red staining and enzymatic activity assays further confirmed the enhanced secretion of extracellular enzymes and the increased cell wall-degrading capacity of BBR–A. On detached blueberry leaves, seedlings, and fruits, BBR–A treatment significantly delayed lesion expansion and reduced disease severity. Metabolomic profiling further demonstrated that BBR–A induces the marked accumulation of phenolic compounds, polyamines, and other antioxidant- and immunity-related metabolites in blueberry leaves, thereby maintaining host redox homeostasis and enhancing stress resilience. Collectively, these findings indicate that T. asperellum BBR–A effectively suppresses B. cinerea through multiple mechanisms, including antagonism, mycoparasitism, metabolic regulation, and the induction of plant defense responses, highlighting its strong potential for development as a biocontrol agent against blueberry gray mold. Full article
(This article belongs to the Section Fungi in Agriculture and Biotechnology)
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20 pages, 16406 KB  
Article
Dihydromyricetin Mitigates Depression-Related Memory Impairments Through Regulation of Hippocampal PKA-CREB-BDNF Pathway in Mice
by Le Wang, Yuxiang Wang, Hao Chen, Zhiming He, Yanping Long, Lisha Yu, Chuli Xiao, Jiaxiu Zhou, Xudong Yu, Qingshan Long and Xinhua Shu
Biology 2026, 15(14), 1144; https://doi.org/10.3390/biology15141144 - 14 Jul 2026
Viewed by 423
Abstract
Background: Depression-associated memory impairment is a clinically significant comorbidity that responds poorly to conventional antidepressants. Dihydromyricetin (DHM), a natural dihydroflavonoid, exhibits neuroprotective and antidepressant-like effects, but its impact on stress-induced memory deficits and the underlying mechanisms remain unclear. Methods: A chronic restraint stress [...] Read more.
Background: Depression-associated memory impairment is a clinically significant comorbidity that responds poorly to conventional antidepressants. Dihydromyricetin (DHM), a natural dihydroflavonoid, exhibits neuroprotective and antidepressant-like effects, but its impact on stress-induced memory deficits and the underlying mechanisms remain unclear. Methods: A chronic restraint stress (CRS) mouse model was employed. DHM was intraperitoneally administered daily (20 mg/kg bodyweight) for 8 consecutive days. Depression-like behavior and memory functions were assessed with the tail suspension test, the object recognition memory (ORM) task, and the Y-maze test. Network pharmacology, molecular docking, and molecular dynamics (MD) simulations were integrated to predict potential targets and associated signal pathways. Expression of hippocampal PKA, p-CREB, CREB, and BDNF was measured through Western blotting. Results: CRS significantly increased immobility time in the tail suspension test and impaired both recognition memory (ORM) and spatial working memory (Y-maze), without affecting locomotor activity. DHM treatment effectively reversed behavioral despair and memory deficits. Network pharmacology identified 47 intersecting targets between DHM and depression-related memory impairment, with CREB1, ESR1 and NOS1 as core hub nodes. KEGG enrichment particularly implicated the involvement of the cAMP signaling pathway and other signaling pathways, which are associated with depression and/or memory impairment. Molecular docking predicted strong binding affinities of DHM to CREB1 (−9.225 kcal/mol), NOS1 (−9.113 kcal/mol) and ESR1 (−7.903 kcal/mol). MD simulations confirmed the thermodynamic stability of DHM-ESR1 and DHM-NOS1 complexes. Western blot analysis demonstrated that DHM treatment significantly increased the levels of hippocampal PKA, p-CREB and BDNF, without altering total CREB expression in CRS mice. Conclusions: DHM alleviated CRS-induced depression-like behaviors and memory deficits, possibly through regulation of multiple signaling pathways, including the hippocampal PKA-CREB-BDNF signaling pathway. These findings highlight DHM as a promising natural therapeutic candidate for depression-associated cognitive impairment. Full article
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25 pages, 2763 KB  
Article
Robust Trust-Aware Federated Learning for Privacy-Preserving Distributed Intelligence in Resource-Constrained IoT Systems: A Blockchain-Assisted Architecture
by Manuel J. C. S. Reis, Carlos Serôdio and Frederico Branco
Electronics 2026, 15(14), 3069; https://doi.org/10.3390/electronics15143069 - 13 Jul 2026
Viewed by 370
Abstract
The rapid expansion of Internet of Things (IoT) ecosystems has intensified the need for distributed intelligence mechanisms that reduce direct raw-data exposure while remaining resilient to adversarial manipulation. Federated learning (FL) addresses part of this challenge by enabling collaborative model training without centralizing [...] Read more.
The rapid expansion of Internet of Things (IoT) ecosystems has intensified the need for distributed intelligence mechanisms that reduce direct raw-data exposure while remaining resilient to adversarial manipulation. Federated learning (FL) addresses part of this challenge by enabling collaborative model training without centralizing raw data, but it remains vulnerable to malicious client behavior, particularly model poisoning attacks that can substantially degrade global model quality. This paper investigates a blockchain-assisted, trust-aware FL framework for privacy-aware distributed intelligence in resource-constrained IoT systems, where the blockchain layer is used to support trust coordination, auditability, traceability, and tamper-resistant metadata recording rather than to directly improve predictive performance. The empirical study compares six aggregation strategies: FedAvg, coordinate-wise Median, Trimmed Mean, FLTrust, trust-aware weighted aggregation, and a hybrid trust-trimmed mean method. The primary evaluation is conducted on the UCI Human Activity Recognition (UCI HAR) dataset under Dirichlet-based non-IID client partitioning α = 0.1 and α = 1.0, partial client participation, and sign-flip model poisoning. Each configuration is evaluated over five independent runs. Under the severe 40% malicious-client stress test, FLTrust achieves the strongest mean robustness among the evaluated methods, reaching 0.4195 ± 0.1295 accuracy and 0.3108 ± 0.1294 macro-F1 for α = 0.1, and 0.6472 ± 0.0725 accuracy and 0.6014 ± 0.0949 macro-F1 for α = 1.0. In lower-intensity attack controls with 10% and 20% malicious clients, the trust-aware and hybrid trust-trimmed strategies are the most competitive, achieving the highest or near-highest mean performance without requiring a clean server-side reference set. Mechanism-level analysis shows that FLTrust is particularly effective in the severe setting because its reference-based scoring assigns near-zero weights to malicious clients, whereas trust-aware and hybrid methods rely on relative update consistency and are more affected by the interaction between poisoning and statistical heterogeneity. Globally, the results indicate that no single aggregation rule dominates all adversarial regimes. Instead, reference-based trust provides strong protection under severe poisoning, while trust-aware and hybrid aggregation offer competitive root-free alternatives under lower attack intensities. The findings also clarify that the privacy-preserving scope of the framework derives from FL-based data locality and does not constitute a formal cryptographic privacy guarantee. Full article
(This article belongs to the Special Issue Data Privacy Protection in Blockchain Systems)
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20 pages, 1996 KB  
Article
Multi-Targeted Anti-Alzheimer’s Effects of Tri-Sannibat-Phol: Biological Evaluation, Behavioral Validation, and LC-MS/MS Phytochemical Profiling
by Pitchayakarn Takomthong, Pornthip Waiwut, Sumet Kongkiatpaiboon, Khemjira Phemphunananchai and Chantana Boonyarat
Pharmaceuticals 2026, 19(7), 1063; https://doi.org/10.3390/ph19071063 - 9 Jul 2026
Viewed by 491
Abstract
Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by oxidative stress, cholinergic dysfunction, and amyloid-β (Aβ) aggregation. Tri-Sannibat-Phol (TSB), a classical Thai polyherbal formulation comprising Piper retrofractum fruit, Ocimum tenuiflorum root, and Piper nigrum root, has been traditionally used for its [...] Read more.
Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by oxidative stress, cholinergic dysfunction, and amyloid-β (Aβ) aggregation. Tri-Sannibat-Phol (TSB), a classical Thai polyherbal formulation comprising Piper retrofractum fruit, Ocimum tenuiflorum root, and Piper nigrum root, has been traditionally used for its medicinal properties, yet its anti-AD potential has never been scientifically evaluated. Methods: The therapeutic potential of TSB was investigated through in vitro bioassays including antioxidant, acetylcholinesterase (AChE) inhibitory, and anti-Aβ aggregation assays, alongside neuroprotective evaluation in H2O2-induced SH-SY5Y neuroblastoma cells. Acute oral toxicity was assessed in male ICR mice in accordance with OECD Guideline 420. Cognitive-enhancing effects were evaluated using the modified Y-maze, Novel Object Recognition, and Morris Water Maze tests in a scopolamine-induced amnesic mouse model. LC-MS/MS analysis was performed for phytochemical characterization and chemical standardization of the formulation. Results: TSB demonstrated significant antioxidant activity, AChE inhibitory activity, and anti-Aβ aggregation effects, with P. nigrum and O. tenuiflorum identified as the primary contributing components. Neuroprotective effects were confirmed in H2O2-induced SH-SY5Y cells, where TSB significantly improved cell viability across concentrations of 1–100 µg/mL. Acute oral toxicity assessment revealed an LD50 exceeding 2000 mg/kg, indicating a favorable safety profile. In vivo behavioral studies demonstrated that TSB at medium-to-high doses significantly reversed scopolamine-induced cognitive deficits across all three behavioral tests. LC-MS/MS analysis identified thirteen piperidine alkaloids, with piperine as the dominant constituent at 17.61 ± 0.80% w/w, proposed as the primary bioactive driver and chemical marker for future quality standardization. Conclusions: These findings suggest that TSB exerts multi-targeted anti-AD effects through complementary mechanisms, supporting its potential as a traditional medicine-based therapeutic candidate for further preclinical and clinical investigation. Full article
(This article belongs to the Section Natural Products)
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27 pages, 12888 KB  
Article
Prenylated p-Coumaric Acid Derivatives Mitigate Neurobehavioral and Neuroinflammatory Alterations Associated with Experimental Colitis
by Camila A. Cazarin, Bruna Longo, Eduarda R. Bauer, Morgana S. Machado, Maria I. Basílio, Tauani C. S. França, Thiago F. de Q. e Silva, Benhur J. Cury, Larissa Venzon, Ana C. dos Santos, Heloísa I. Eisendecker, Luiza F. Corsi, Alex W. Valachinski, Sérgio F. de Andrade, Victor P. Ribeiro, Matheus H. Tanimoto, Jairo K. Bastos, Luísa M. da Silva and Márcia M. de Souza
Int. J. Mol. Sci. 2026, 27(13), 5929; https://doi.org/10.3390/ijms27135929 - 1 Jul 2026
Viewed by 493
Abstract
Inflammatory bowel disease is an inflammatory disorder associated with systemic immune activation, contributing to neuroinflammation, behavioral impairments and disruption of the gut–brain axis. The present study investigated the effects of p-Coumaric acid derivatives: Artepillin C (ART-C), Baccharin (BAC), and Drupanin (DRU) on colonic [...] Read more.
Inflammatory bowel disease is an inflammatory disorder associated with systemic immune activation, contributing to neuroinflammation, behavioral impairments and disruption of the gut–brain axis. The present study investigated the effects of p-Coumaric acid derivatives: Artepillin C (ART-C), Baccharin (BAC), and Drupanin (DRU) on colonic damage, behavioral alterations, and oxidative stress in a dextran sulfate sodium (DSS)-induced colitis by administration of 3% DSS. Mice were treated with p-Coumaric acid derivatives (0.3, 1, or 3 mg/kg, p.o.), and disease activity index and colon length were evaluated as clinical parameters. Behavioral assessments included the open field test, novel object recognition test, elevated plus maze, and tail suspension test. Oxidative stress and inflammatory markers were quantified in colon, serum, cortex, and hippocampus, alongside histological analysis of colonic tissue. DSS administration induced clinical and histopathological alterations, increased oxidative stress, and impaired recognition memory, as well as anxiety- and depressive-like behaviors. p-Coumaric acid derivatives attenuated colonic damage, preserved tissue architecture, improved recognition memory, and reduced anxiety- and depressive-like behaviors, particularly at higher doses. These effects were associated with modulation of antioxidant defenses and reduction of lipid peroxidation and inflammatory markers. p-Coumaric acid derivatives exert protective effects in DSS-induced colitis, highlighting their potential as therapeutic agents for intestinal and neurobehavioral alterations associated with IBD. Full article
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52 pages, 4782 KB  
Article
Stress-Based Assessment of Bio-Inspired Phosphene Vision Encoding: Trade-Offs Among Performance, Residual Proxy Safety Burden, and Topology-Based Representation Metrics
by Youngseok Lee
Biomimetics 2026, 11(7), 455; https://doi.org/10.3390/biomimetics11070455 - 1 Jul 2026
Viewed by 443
Abstract
Phosphene-based visual neuroprostheses require encoding schemes that preserve task-relevant information while remaining feasible under safety-constrained stimulation. This study proposes a stress-based evaluation framework that reframes phosphene encoder assessment as a tri-objective operating-envelope problem rather than a single-metric comparison. Four representative encoders—rate, sparse, temporal, [...] Read more.
Phosphene-based visual neuroprostheses require encoding schemes that preserve task-relevant information while remaining feasible under safety-constrained stimulation. This study proposes a stress-based evaluation framework that reframes phosphene encoder assessment as a tri-objective operating-envelope problem rather than a single-metric comparison. Four representative encoders—rate, sparse, temporal, and optim—were evaluated under structured perturbations using two simulated prosthetic-vision(SPV) benchmarks: EMNIST Letters for symbolic recognition and a COCO-derived balanced subset for a reduced four-class COCO-derived image-level classification task. The final experimental configuration used 20,000/3000/3000 train/validation/test samples for EMNIST and 4000/1000/1000 for the COCO-derived benchmark. The framework combined structured stress sweeps, residual proxy safety-burden analysis, topology-based representation metrics, and stress-integrated utility summaries within a simulation-based evaluation setting. The results showed that clean-conditioning accuracy alone was insufficient to predict encoder behavior under stress. EMNIST exhibited broad operator-dependent degradation, whereas the COCO-derived benchmark showed a lower but more compressed performance regime. Residual proxy safety burden was only loosely aligned with performance, with moderate dissociation between performance and residual proxy safety burden in EMNIST and weaker alignment between these two axes in the COCO-derived benchmark. In the point-estimate utility summaries, the sparse encoder tended to yield comparatively favorable tri-objective utility values within the present single-run simulation-based framework, simplified SPV percept-synthesis operator, and fixed benchmark-specific decoder setting, primarily because it maintained an almost negligible residual proxy safety burden while preserving competitive performance and topology-based representation metrics. Topology-based analysis further indicated that topology-based representation metrics largely tracked task degradation in EMNIST, whereas topology-based representation metrics showed larger relative variation than decoder accuracy within the evaluated simulation setting under degraded COCO-derived conditions. Taken together, these findings provide an exploratory, benchmark-specific assessment suggesting that phosphene encoder evaluation may benefit from a multi-axis operating-envelope-oriented analysis that jointly considers stressed functional performance, residual proxy safety burden, and topology-based representation metrics within the present simplified SPV and fixed-decoder evaluation setting. These results should therefore be interpreted as simulation-level, configuration-dependent observations under a simplified SPV percept-synthesis operator, with safety-related quantities treated as residual proxy safety-burden summaries rather than as direct physiological, electrochemical, clinical, or implant-specific safety measurements. Full article
(This article belongs to the Special Issue Bionic Vision Applications and Validation)
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14 pages, 1274 KB  
Article
Adolescent Δ9-THC Exposure Differentially Affects Mice Depending on Their Personality
by Dilorom Begmatova, Liudmila Vinnikova, Natalya Zemliana, Kenneth Blum, Panayotis K. Thanos, Natalya M. Kogan and Albert Pinhasov
Pharmaceuticals 2026, 19(7), 1009; https://doi.org/10.3390/ph19071009 - 29 Jun 2026
Viewed by 334
Abstract
Background: Adolescence is a sensitive period for brain maturation during which exposure to Δ9-tetrahydrocannabinol (THC) can induce long-lasting neurobehavioral alterations. Yet, preclinical and clinical studies report inconsistent long-term outcomes of adolescent THC exposure, ranging from clear impairments to apparently normalizing effects. [...] Read more.
Background: Adolescence is a sensitive period for brain maturation during which exposure to Δ9-tetrahydrocannabinol (THC) can induce long-lasting neurobehavioral alterations. Yet, preclinical and clinical studies report inconsistent long-term outcomes of adolescent THC exposure, ranging from clear impairments to apparently normalizing effects. We hypothesize that these discrepancies reflect stable individual differences in stress-coping abilities. Methods: To test this, selectively bred Dominant (Dom; stress-resilient, risk-prone) and Submissive (Sub; stress-vulnerable, depressive-like) Sabra mice received THC or vehicle during adolescence and were assessed in adulthood. Results: Anxiety-like and exploratory behavior, measured in the hole-board test, were differentially affected by THC as a function of stress vulnerability: in Sub mice, THC increased exploration and reduced anxiety-like behavior, whereas in Dom mice THC produced the opposite pattern. Recognition memory, evaluated by the novel object recognition test, showed modest, line-dependent alterations. Sensitivity to N-methyl-D-aspartate (NMDA) receptor hypofunction, a widely used index of vulnerability to schizophrenia-like symptoms, was examined using MK-801-induced locomotion. Adolescent THC potentiated MK-801-evoked hyperlocomotion in Dom mice but attenuated it in Sub mice. Conclusions: In the context of increasing medical and recreational cannabis exposure, these in vivo findings suggest that stress-vulnerability-related traits may be an important variable to consider in future preclinical and translational studies of adolescent THC exposure. Full article
(This article belongs to the Section Natural Products)
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27 pages, 9193 KB  
Article
Mulberroside A Alleviates Scopolamine-Induced Cognitive Deficits by Suppressing Neuroinflammation and Oxidative Stress via the Dubosiella-Associated Microbiota–Gut–Brain Axis
by Jin Li, Shirui Cheng, Wenqi Zhang, Shourong Qiao, Luzhi Zhang, Mengxu Yao, Yunxia Zhang, Biao Wang and Changjing Wu
Biology 2026, 15(13), 1030; https://doi.org/10.3390/biology15131030 - 28 Jun 2026
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Abstract
Mulberroside A (MsA) possesses neuroprotective effects, but whether it alleviates Alzheimer’s disease (AD)-like cognitive impairment through the microbiota–gut–brain axis remains unclear. Using a scopolamine-induced mouse model of acute cognitive impairment (male ICR mice, n = 10/group), we demonstrated that daily administration of MsA [...] Read more.
Mulberroside A (MsA) possesses neuroprotective effects, but whether it alleviates Alzheimer’s disease (AD)-like cognitive impairment through the microbiota–gut–brain axis remains unclear. Using a scopolamine-induced mouse model of acute cognitive impairment (male ICR mice, n = 10/group), we demonstrated that daily administration of MsA (10, 20, and 30 mg/kg/day) for 5 weeks significantly ameliorated cognitive performance in novel object recognition and Morris water maze tests. At the optimal dose (30 mg/kg/day), MsA suppressed hippocampal microglial activation, reduced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and attenuated oxidative stress by decreasing malondialdehyde (MDA) while restoring superoxide dismutase (SOD) and glutathione (GSH) levels. MsA also strengthened intestinal barrier integrity (ZO-1, occludin) and significantly altered the gut microbiota, notably increasing the beneficial genus Dubosiella. Brain metabolomics indicated that MsA reversed scopolamine-induced metabolic disturbances, mainly restoring phospholipid balance. Correlation analysis demonstrated a strong gut–brain connection, with Dubosiella abundance positively associated with neuroprotective phospholipids and negatively with stress markers. Furthermore, fecal microbiota transplantation from MsA-treated donors successfully replicated these behavioral improvements in recipient mice, underscoring the functional involvement of the reshaped microbiome rather than a simple autonomous recovery. These results suggest that MsA alleviates AD-like cognitive impairment by reducing neuroinflammation and oxidative stress through microbiota remodeling, enhancing the intestinal barrier, and modulating the Dubosiella-associated gut–metabolite–brain axis, making MsA a promising multi-target nutraceutical for ameliorating AD-like cognitive deficits. Full article
(This article belongs to the Section Neuroscience)
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24 pages, 7309 KB  
Article
Protective Effects of Bacopa monnieri Extract, Mixed Thai Berry Extract and Their Combination Against Chronic Unpredictable Mild Stress-Induced Behavioral Changes in Rats
by Phichsinee Rerkshanandana, Sutisa Nudmamud-Thanoi, Kalyarut Phumlek, Pailada Tiemtad, Prapapan Temkitthawon, Jureepon Roboon, Paweena Kaewman, Wanfrutkon Waehama, Plaiyfah Janthueng, Wiyada Khangkhachit, Sasimontra Timjan and Kornkanok Ingkaninan
Pharmaceuticals 2026, 19(7), 981; https://doi.org/10.3390/ph19070981 - 24 Jun 2026
Viewed by 626
Abstract
Background/Objectives: Chronic stress contributes to anxiety disorders and cognitive impairment, while effective multi-target therapeutic strategies remain limited. This study investigated the effects of a standardized extract prepared from the aerial parts of Bacopa monnieri (L.) Wettst. (Brahmi) extract and an anthocyanin-rich mixed Thai [...] Read more.
Background/Objectives: Chronic stress contributes to anxiety disorders and cognitive impairment, while effective multi-target therapeutic strategies remain limited. This study investigated the effects of a standardized extract prepared from the aerial parts of Bacopa monnieri (L.) Wettst. (Brahmi) extract and an anthocyanin-rich mixed Thai berry extract, administered individually and in combination, in a chronic unpredictable mild stress (CUMS) rat model. Methods: Extracts derived from Morus alba L. (mulberry), Antidesma ghaesembilla Gaertn. (mamao), and Syzygium nervosum DC. (ma-kiang) were characterized for anthocyanin and phenolic contents, antioxidant activities, and cyanidin-3-O-glucoside levels using HPLC. Male Sprague Dawley rats were subjected to a 14-day CUMS protocol and treated with Brahmi extract, mixed Thai berry extract, or their combinations. Behavioral assessments included the open-field test, elevated plus maze, and novel object recognition test. Histopathological evaluation of the prefrontal cortex and hippocampus was also performed. Results: Brahmi extract and mixed Thai berry extract attenuated selected anxiety-related behaviors and improved recognition memory-related parameters in CUMS-exposed rats. The low-dose berry extract produced the most consistent behavioral improvements, whereas combination-treated groups showed greater histological preservation. Histopathological analysis revealed reduced neuronal degeneration and improved tissue organization in the prefrontal cortex and hippocampus of treated animals. Conclusions: These findings support the potential therapeutic relevance of Bacopa monnieri and anthocyanin-rich Thai berry extracts under chronic stress conditions, with differential effects observed between individual and combination treatments. Full article
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