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Hericium erinaceus extracts promote neuronal differentiation and excitability through nootropic metabolite activity

Biomedicine & Pharmacotherapy 2025年 188卷 118204-118204页

作者： Brandalise, Federico Priori, Erica Cecilia Giammello, Francesca Venuti, MariaTeresa Ratto, Daniela Goppa, Lorenzo Locatelli, Carlo Alessandro Savino, Elena Roda, Elisa Rossi, Paola Department of Biomedical Sciences Division of Neuroscience and Clinical Pharmacology University of Cagliari Cittadella Universitaria di Monserrato Monserrato 09042 Italy Department of Biology and Biotechnology “L. Spallanzani” University of Pavia Pavia 27100 Italy PhD Program in Genetics Molecular and Cellular Biology University of Pavia Italy Department of Earth and Environmental Sciences (DSTA) University of Pavia Pavia 27100 Italy PhD Program in Earth and Environmental Sciences University of Pavia Italy Laboratory of Clinical & Experimental Toxicology Pavia Poison Centre National Toxicology Information Centre Toxicology Unit Istituti Clinici Scientifici Maugeri IRCCS Pavia Pavia 27100 Italy

AbstractThis study investigates the effects of a blend of Hericium erinaceus (lion's mane mushroom) extract on the differentiation of SH-SY5Y cells, a human neuroblastoma cell line, revealing potential therapeutic implications for neuroblastoma management. Treatment with this blend induced cells differentiation towards a neuron-like profile, as evidenced by enhanced neuronal excitability and upregulation of neuronal markers, such as βIII-tubulin and synaptotagmin. Additionally, the treatment significantly reduced PCNA, a key regulator of proliferation, alongside a decrease in stemness markers, indicating a shift toward a more mature and less proliferative phenotype. These findings demonstrate the ability of Hericium erinaceus to promote neuronal differentiation and inhibit proliferation in neuroblastoma cells, highlighting its therapeutic potential for managing neuroblastoma and potentially other neurological disorders. The results suggest that Hericium erinaceus may serve as a promising candidate for the development of novel neuroregenerative therapies.

关键词： TPA 12-O tetradecanoylphorbol-13-acetate He Hericium erinaceus MTT assay 3 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay Cm Membrane capacitance Rm Membrane resistance Vm Resting membrane potential TTX Tetrodotoxin VGSC Voltage-gated sodium channel I-V plots Current-voltage plots SNARE Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor PCNA Proliferating Cell Nuclear Antigen Neuroblastoma SH-SY5Y Hericium erinaceus Neuronal differentiation Patch clamp Voltage-gated sodium currents Cell proliferation Action potential Erinacines Hericenones Voltage-Gated Sodium Channel

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Refining the link between obesity and heart failure: insights from GLP-1 receptor agonist trials and studies adopting direct adiposity measures

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Cardiovascular Diabetology 2025年第1期24卷 1-17页

作者： Pugliese, Nicola Riccardo Paneni, Francesco Tricò, Domenico Bacca, Alessandra Violet De Biase, Nicolò Dalpiaz, Hermann Mengozzi, Alessandro Virdis, Agostino Ghiadoni, Lorenzo Taddei, Stefano Kreutz, Reinhold Tsioufis, Konstantinos Masi, Stefano Department of Clinical and Experimental Medicine University of Pisa Pisa Italy Center for Translational and Experimental Cardiology (CTEC) University Hospital Zurich and University of Zurich Zurich Switzerland Department of Cardiology University Heart Center University Hospital Zurich Zurich Switzerland Unit of Internal Medicine Azienda Ospedaliera Universitaria Pisana Pisa Italy PhD Program in Clinical and Translational Science Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy Department of Surgical Medical and Molecular Pathology and Critical Area University of Pisa Pisa Italy Institute of Clinical Pharmacology and Toxicology Charité–Universitätsmedizin Berlin Berlin Germany Hippokration Hospital National and Kapodistrian University of Athens Athens Greece

Overweight and obesity are major risk factors for heart failure (HF), contributing to its development through metabolic, neurohormonal, haemodynamic, and inflammatory alterations. While overweight/obesity increases the risk of developing HF, its impact on patient outcomes remains complex. The “obesity paradox” suggests that a higher BMI may be associated with improved survival in patients with established HF. However, recent GLP-1 receptor agonist (GLP-1 RA) trials suggest that intentional weight loss positively influences outcomes in overweight/obese patients with HF. This seemingly contradictory evidence highlights the need for a deeper understanding of the mechanisms linking adiposity to HF outcomes. A more precise characterization of adiposity phenotypes using alternative and accurate measures of pathological fat accumulation is crucial in identifying individuals who may benefit most from anti-obesity treatments. In this context, recent research underscores the role of epicardial adipose tissue (EAT) in HF pathophysiology, as it directly influences cardiac function and structure through inflammatory, metabolic, and mechanical effects. This narrative review summarises current evidence on the impact of weight loss on HF outcomes, focusing on recent GLP-1 RA trial results. Additionally, it highlights epidemiological and molecular data supporting EAT as a novel adiposity measure that might allow refining patient selection for pharmacological weight-loss treatments. Finally, it emphasizes the need for future research to identify causal pathways linking alternative measures of visceral fat accumulation to HF outcomes. These efforts will be essential in optimizing the benefits of novel weight-loss treatments, ensuring effective and individualized therapeutic strategies for overweight or obese patients with HF.

关键词： Epicardial adipose tissue Epigenetic GLP-1 RA Heart failure Obesity

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Principles and Methods in toxicology

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International Journal of toxicology 2001年第5期20卷 333 - 335页

作者： Udayan M. Apte Kartik Shankar Vishal S. Vaidya Pallavi B. Limaye Sharmilee Sawant Doctoral Students Training program in Toxicology Harihara M. Mehendale PhD Professor and DeGree Chair in Toxicology Department of Toxicology College of Pharmacy The University of Louisiana at Monroe Monroe Louisiana USA

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Major Depressive Disorder in Long COVID and Exposure to Pro-Inflammatory Cytokines During Infection by SARS-CoV-2

Psychiatric Research and Clinical Practice

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Psychiatric Research and Clinical Practice 2025年第0期

作者： Guillen-Burgos, Hernan F. Gálvez-Flórez, Juan F. Moreno-López, Sergio Wong, Sabrina Kwan, Angela T. H. Ramirez-Posada, Mariana Anaya, Juan-Manuel McIntyre, Roger S. Centro de Investigaciones en Ciencias de la Vida Universidad Simón Bolívar Center for Clinical and Translational Research Barranquilla Colombia Faculty of Medicine Universidad El Bosque Center for Clinical and Translational Research Bogotá Colombia Department of Psychiatry and Mental Health Pontificia Universidad Javeriana PhD Program in Neuroscience Hospital Universitario San Ignacio Bogota Colombia Universidad El Bosque Bogotá Colombia Zerenia Clinic. Consultation - Liaison Psychiatric Unit Bogotá Colombia Faculty of Medicine Universidad de Los Andes Bogotá Colombia Mood Disorders Psychopharmacology Unit University Health Network Toronto ON Canada Department of Pharmacology and Toxicology University of Toronto Toronto ON Canada Brain and Cognition Discovery Foundation Toronto ON Canada Faculty of Medicine University of Ottawa Ottawa ON Canada Coosalud IPS Research and Innovation Center and Universidad de la Costa Barranquilla Colombia Department of Psychiatry and Pharmacology University of Toronto Toronto ON Canada

Objective: Major Depressive Disorder (MDD) is common in long COVID syndrome;however, the neurobiological mechanisms are unclear. An immune activation response has been associated with COVID-19 severity as well as in MDD. We hypothesize that high levels of pro-inflammatory cytokines during SARS-CoV-2 infection may be associated with new-onset MDD and severe outcomes such as treatment-resistant depression (TRD) and risk of suicide ideation and behavior (SI/SB). Methods: A case-control nested to a cohort study was carried out on a total of 678 COVID-19 survivors (MDD = 184 vs. non-MDD = 494). A pro-inflammatory panel of serum levels of cytokines (IL-1β, IL-4, IL-6, IL-8, IL-13, IL-17α, TNF-α) was evaluated during COVID-19 hospitalization and severe outcomes such as TRD and SI/SB were assessed in individuals with new onset of MDD after hospital discharge compared to non-MDD COVID-19 survivors. Results: High levels of pro-inflammatory cytokines during SARS-CoV-2 infection were identified in MDD participants compared to non-MDD subgroups during long COVID. These differences were sustained also for TRD and SI/SB severity outcomes. There is a mild association of high levels of pro-inflammatory cytokines and MDD, TRD, and SI/SB. Conclusion: High levels of pro-inflammatory cytokines during severe or critical COVID-19 exposure may explain long COVID associated MDD and thus severe outcomes such as TRD and SI/SB. Relevance to clinical practice: Identifying elevated pro-inflammatory cytokines during COVID-19 as a risk factor for MDD and severe outcomes underscores the need for early screening and targeted treatments in long COVID. Monitoring cytokine levels may help clinicians predict and manage TRD and SI/SB in this population, improving long-term psychiatric outcomes. © 2025 The Author(s). Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC on behalf of American Psychiatric Association.

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Reply to "Efficacy of unithiol (2,3-dimercaptopropanesulfonate) and acetylcysteine in a patient with arthroplastic cobalt toxicity"

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Clinical toxicology (Philadelphia, Pa.) 2023年第5期61卷 412-413页

作者： Monica Carnovale Davide Lonati Azzurra Schicchi Valeria Margherita Petrolini Carlo Alessandro Locatelli Toxicology Unit Pavia Poison Control Centre - National Toxicology Information Centre - Clinical and Experimental Lab Istituti Clinici Scientifici Maugeri IRCCS Pavia Italy. Postgraduate School of Pharmacology and Clinical Toxicology University of Pavia Pavia Italy. Experimental Medicine PhD Program University of Pavia Pavia Italy.

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Passive eye movements induced by electromagnetic force(EMF) in rats

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Zoological Research 2019年第3期40卷 211-218页

作者： Yue Yu Jun Huang Chun-Ming Zhang Tian-Wen Chen David S.Sandlin Shao-Xun Wang Alberto A.Arteaga Jerome Allison Yang Ou Susan Warren Paul May Hong Zhu Wu Zhou Departments of Otolaryngology and Communicative Sciences University of Mississippi Medical CenterJackson MS 39216USA Department of Otolaryngology First Affiliated HospitalShanxi Medical UniversityTaiyuan Shanxi 030001China MD/PhD Program University of Mississippi Medical CenterJackson MS 39216USA Pharmacology and Toxicology University of Mississippi Medical CenterJackson MS 39216.USA Neurobiology and Anatomical Sciences University of Mississippi Medical CenterJackson MS 39216USA Neurology University of Mississippi Medical CenterJackson MS 39216USA

Accurate information on eye position in the orbit is available from visual feedback,efference copy of the oculomotor commands and proprioceptive signals from the extraocular muscles (EOM).Whereas visual feedback and oculomotor commands have been extensively studied,central processing of EOM proprioceptive signals remains to be elucidated.A challenge to the field is to develop an approach to induce passive eye movements without physically contacting the eyes.A novel method was developed to generate passive eye movements in rats.A small rare-earth magnet disk (0.7 mm diameter,0.5 mm thickness) was attached to the surface of a rat's eyeball.A metal rod (5 mm diameter) wrapped with an electromagnetic (EM) coil was placed near the magnet (8-15 mm).By passing currents to the EM coil,electromagnetic force (EMF) was generated and acted upon the magnet and induced passive eye *** EMF induced well-defined passive eye movements,whose directions were dependent on current polarity and amplitudes and peak velocities were dependent on current intensity and *** velocities of the EMF-induced eye movements were linearly related to amplitudes,exhibiting main sequence relationships similar to that of saccades in awake rats and eye movements induced by electrical microstimulation of the abducens nucleus in anesthetized *** examination showed that repetitive EMF stimulations did not appear to result in damages in the EOM *** results validated the EMF approach as a novel tool to investigate EOM proprioceptive signals and their roles in visual localization and gaze control.

关键词： Eye movement Proprioception Extraocular muscles Stretch reflex

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Overcoming Cytosolic Delivery Barriers of Proteins Using Denatured Protein-Conjugated Mesoporous Silica Nanoparticles

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ACS Applied Materials and Interfaces 2023年第1期15卷 432-451页

作者： Dembélé, Julien Liao, Jou-Hsuan Liu, Tsang-Pai Chen, Yi-Ping Graduate Institute of Biomedical Materials & Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Laboratory of Toxicology Environment and Health Doctorate School of Health University Joseph Ki-Zerbo Ouaga03 BP 7021 Burkina Faso Department of Chemistry National Taiwan University Taipei10617 Taiwan Department of Surgery Mackay Memorial Hospital Taipei10449 Taiwan Graduate Institute of Nanomedicine and Medical Engineering Taipei Medical University Taipei11031 Taiwan International PhD Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan

Intracellular delivery of therapeutic proteins has increased advantages over current small-molecule drugs and gene therapies, especially in therapeutic efficacies for a broad spectrum of diseases. Hence, developing the protein therapeutics approach provides a needed alternative. Here, we designed a mesoporous silica nanoparticle (MSN)-mediated protein delivery approach and demonstrated effective intracellular delivery of the denatured superoxide dismutase (SOD) protein, overcoming the delivery challenges and achieving higher enzymatic activity than native SOD-conjugated MSNs. The denatured SOD-conjugated MSN delivery strategy provides benefits of reduced size and steric hindrance, increased protein flexibility without distorting its secondary structure, exposure of the cell-penetrating peptide transactivator of transcription for enhanced efficient delivery, and a change in the corona protein composition, enabling cytosolic delivery. After delivery, SOD displayed a specific activity around threefold higher than in our previous reports. Furthermore, the in vivo biosafety and therapeutic potential for neuron therapy were evaluated, demonstrating the biocompatibility and the effective antioxidant effect in Neuro-2a cells that protected neurite outgrowth from paraquat-induced reactive oxygen species attack. This study offers an opportunity to realize the druggable possibility of cytosolic proteins using MSNs. © 2022 American Chemical Society.

关键词： Peptides

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Fipronil disturbs the antigen-specific immune responses and GABAergic gene expression in the ovalbumin-immunized BALB/c mice

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BMC Veterinary Research 2024年第1期20卷 30页

作者： Kuo, Jui-Fang Cheng, Yin-Hua Tung, Chun-Wei Wang, Chia-Chi School of Veterinary Medicine National Taiwan University Taipei Taiwan PhD Program in Toxicology Kaohsiung Medical University Kaohsiung Taiwan Institute of Biotechnology and Pharmaceutical Research National Health Research Institutes Miaoli County Taiwan

Background: Fipronil (FPN) is a broad-spectrum pesticide and commonly known as low toxicity to vertebrates. However, increasing evidence suggests that exposure to FPN might induce unexpected adverse effects in the liver, reproductive, and nervous systems. Until now, the influence of FPN on immune responses, especially T-cell responses has not been well examined. Our study is designed to investigate the immunotoxicity of FPN in ovalbumin (OVA)-sensitized mice. The mice were administered with FPN by oral gavage and immunized with OVA. Primary splenocytes were prepared to examine the viability and functionality of antigen-specific T cells ex vivo. The expression of T cell cytokines, upstream transcription factors, and GABAergic signaling genes was detected by qPCR. Results: Intragastric administration of FPN (1–10 mg/kg) for 11 doses did not show any significant clinical symptoms. The viability of antigen-stimulated splenocytes, the production of IL-2, IL-4, and IFN-γ by OVA-specific T cells, and the serum levels of OVA-specific IgG₁ and IgG_2a were significantly increased in FPN-treated groups. The expression of the GABAergic signaling genes was notably altered by FPN. The GAD67 gene was significantly decreased, while the GABAR β2 and GABAR δ were increased. Conclusion: FPN disturbed antigen-specific immune responses by affecting GABAergic genes in vivo. We propose that the immunotoxic effects of FPN may enhance antigen-specific immunity by dysregulation of the negative regulation of GABAergic signaling on T cell immunity. © 2024, The Author(s).

关键词： Antigen-specific immune responses Fipronil GABAergic signaling Immunotoxicity Ovalbumin

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TIPdb-3D: The three-dimensional structure database of phytochemicals from Taiwan indigenous plants

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Database 2014年第2014期2014卷 bau055页

作者： Tung, Chun-Wei Lin, Ying-Chi Chang, Hsun-Shuo Wang, Chia-Chi Chen, Ih-Sheng Jheng, Jhao-Liang Li, Jih-Heng School of Pharmacy Kaohsiung Medical University Kaohsiung 80708 Taiwan PhD Program in Toxicology Kaohsiung Medical University Kaohsiung 80708 Taiwan National Environmental Health Research Center National Health Research Institutes Miaoli County 35053 Taiwan

The rich indigenous and endemic plants in Taiwan serve as a resourceful bank for biologically active phytochemicals. Based on our TIPdb database curating bioactive phytochemicals from Taiwan indigenous plants, this study presents a three-dimensional (3D) chemical structure database named TIPdb-3D to support the discovery of novel pharmacologically active compounds. The Merck Molecular Force Field (MMFF94) was used to generate 3D structures of phytochemicals in TIPdb. The 3D structures could facilitate the analysis of 3D quantitative structure-activity relationship, the exploration of chemical space and the identification of potential pharmacologically active compounds using protein-ligand docking. © The Author(s) 2014.

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Facilitating Interdisciplinary Graduate Education: Barriers, Solutions, and Needed Innovations

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Change: The Magazine of Higher Learning 2018年第5期50卷 53-59页

作者： Meredith Welch-Devine Alana Shaw Julie Coffield Nik Heynen Meredith Welch-Devine is the Director of Interdisciplinary and Innovative Initiatives for the University of Georgia Graduate School. In addition to helping develop and administer interdisciplinary programs for the university she has a research interest in interdisciplinary team science and interdisciplinary training.http://***/0000-0001-8519-4585 Alana Shaw received her PhD from the University of Georgia in 2016 and is now the Environmental Coordinator for the Village of Wainwright. Shaw was a student in the interdisciplinary Integrative Conservation program. Julie Coffield recently returned to the faculty after serving as Associate Dean of the Graduate School. She also formerly directed the Interdisciplinary Toxicology Program at UGA. Nik Heynen is the immediate past director of the interdisciplinary Integrative Conservation program.

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关键词： INTERDISCIPLINARY education GRADUATE education HUMAN resources departments STUDENTS TRAINING

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