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Potential protective role of ACE-inhibitors and AT1 receptor blockers against levodopa-induced dyskinesias:a retrospective case-control study

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Neural Regeneration Research 2021年第12期16卷 2475-2478页

作者： Elena Contaldi Luca Magistrelli Anna VMilner Marco Cosentino Franca Marino Cristoforo Comi Movement Disorders Centre Neurology UnitDepartment of Translational MedicineUniversity of Piemonte OrientaleNovaraItaly PhD Program in Medical Sciences and Biotechnology University of Piemonte OrientaleNovaraItaly PhD Program in Clinical and Experimental Medicine and Medical Humanities University of InsubriaVareseItaly Center of Research in Medical Pharmacology University of InsubriaVareseItaly Center for Research in Neuroscience University of InsubriaVareseItaly

Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as *** each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian *** logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs ***-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian *** mean UPDRS part III score was 18.87±7.6 and the median HY stage was *** the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/***,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between *** controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.

关键词： angiotensin-converting enzyme inhibitors AT1 receptor blockers dyskinesias hypertension levodopa motor complications neuroinflammation Parkinson’s disease renin-angiotensin system

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Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative Diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA *** review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease *** examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease *** entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the ***,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal ***,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory *** complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation *** the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease *** research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

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The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions

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Cell Cycle 2023年第21-22期22卷 2485-2503页

作者： Wu, Nian-Siou Ma, I-Chu Lin, Yi-Fan Ko, Huey-Jiun Loh, Joon-Khim Hong, Yi-Ren Department of Education Hsin-Chu Branch National Taiwan University Hospital Hsinchu Taiwan PhD Program in Molecular Medicine National Tsing Hua University Hsinchu Taiwan Division of Neurology China Medical University Hospital Taichung Taiwan Department of Education National Taiwan University Hospital Taipei Taiwan Department of Biochemistry College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Neurosurgery Kaohsiung Medical University Hospital Kaohsiung Taiwan Graduate Institutes of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Biological Sciences National Sun Yat-Sen University Kaohsiung Taiwan Department of Medical Research Kaohsiung Medical University Hospital Kaohsiung Taiwan Center for Cancer Research Kaohsiung Medical University Kaohsiung Taiwan Neuroscience Research Center Kaohsiung Medical University Kaohsiung Taiwan

Recent study had deepened our knowledge of the mitochondrial dynamics to classify mitochondrial fission into two types. To further clarify the relationship between the two distinct fission machinery and the four major adaptors of Drp1, we propose a model of mechanism elucidating the multiple functions of phospho-Drp1 with its adaptors during cell cycle and providing in-depth insights into the molecular basis and evolutionary implications in depth. The model highlights not only the clustering characteristics of different phospho-Drp1 with respective subsets of mitochondrial pro-fission adaptors but also the correlation, crosstalk and shifting between different clustering of phosphorylated Drp1-adaptors during different key fission situations. Particularly, phospho-Drp1 (Ser616) couples with Mff/MiD51 to exert mitochondrial division and phospho-Drp1 (Ser637) couples with MiD49/Fis1 to execute mitophagy in M-phase. We then apply the model to address the relationship of mitochondrial dynamics to Parkinson’s disease (PD) and carcinogenesis. Our proposed model is indeed compatible with current research results and pathological observations, providing promising directions for future treatment design. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

关键词： cell cycle Drp1 Mitochondrial Adaptors mitophagy phosphorylation

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Tactile information from the vibrissal system modulates hippocampal functioning

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Current Research in Neurobiology 2022年 3卷 100034页

作者： Ibarra-Castaneda, Nereida Moy-Lopez, Norma A. Gonzalez-Perez, Oscar Laboratory of Neuroscience School of Psychology University of Colima Colima Mexico Medical Science PhD Program School of Medicine University of Colima Colima Mexico

Most mammals have sensory tactile hairs, also known as whiskers or vibrissae. Traditionally, whiskers are associated with diverse survival skills, including tactile discrimination, distance assessment, food acquisition, gap crossing, and social interaction. Vibrissae functions are processed in the somatosensorial cortex, commonly referred to as the barrel cortex. Hence, most of the whisker-related research has been focused on this cortical region. However, increasing evidence indicates that the vibrissal system modulates several aspects of hippocampal physiology. This graphical review aims to summarize cumulative evidence indicating that whiskers regulate the neural function and cellularity in several hippocampal subfields. Interestingly, lack of whiskers notably affects neuronal firing in CA1 and CA3 hippocampal subfields, alters spatial mapping, impairs navigational skills, modifies cytoarchitecture, and reduces the adult neurogenesis in the dentate gyrus. This evidence extends our understanding of how whiskers are related to hippocampal function and offers insights to explore novel associations between whisker functions and neural plasticity in the hippocampus. © 2022 The Authors

关键词： Adult neurogenesis Barrel cortex Hippocampus Subgranular zone Vibrissae

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The astrocyte LAMP lights a T cell TRAIL of death

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Neuron 2021年第9期109卷 1423-1425页

作者： Johann, Lisa Waisman, Ari Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg University of Mainz Mainz Germany International PhD Program (IPP) of the Institute for Molecular Medicine (IMB) Mainz Mainz Germany Focus Program Translational Neuroscience (FTN) Mainz Mainz Germany Research Center for Immunotherapy (FZI) Mainz Mainz Germany

In a recent issue of Nature, Sanmarco et al. reveal a novel mechanism by which astrocytes maintain an anti-inflammatory state in the central nervous system (CNS). IFNγ released by gut-licensed meningeal NK cells was found to induce TRAIL expression on astrocytes, causing effector T cell apoptosis. © 2021 Elsevier Inc.

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A + T ± status across MCI and dementia due to AD: a clinic-based, retrospective study

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Neurological Sciences 2022年第11期43卷 6547-6550页

作者： Verde, Federico Aiello, Edoardo Nicolò Milone, Ilaria Giacopuzzi Grigoli, Eleonora Dubini, Antonella Ratti, Antonia Poletti, Barbara Ticozzi, Nicola Silani, Vincenzo Department of Neurology and Laboratory of Neuroscience IRCCS Istituto Auxologico Italiano Piazzale Brescia 20 Milan 20149 Italy Department of Pathophysiology and Transplantation “Dino Ferrari Center” Università Degli Studi Di Milano Milan Italy PhD Program in Neuroscience School of Medicine and Surgery University of Milano-Bicocca Via Cadore 48 Monza 20900 Italy Neurology Residency Program Università Degli Studi Di Milano Milan Italy Department of Laboratory Medicine Laboratory of Clinical Chemistry IRCCS Istituto Auxologico Italiano Milan Italy Department of Medical Biotechnology and Translational Medicine Università Degli Studi Di Milano Milan Italy

Background: This study aimed at comparing, within the 2018 NIA-AA amyloidosis/tauopathy/neurodegeneration (ATN) framework, the distribution of T ± profiles across A + patients with MCI and dementia in a retrospective, single-center, clinic-based cohort. Methods: We retrospectively collected data on N = 168 A + patients with either MCI due to AD (N = 50) or probable AD dementia (ADD;N = 118). ATN status was assigned, according to the 2018 NIA-AA framework, based on cerebrospinal fluid (CSF) biomarker concentrations. A χ²-test for independent samples was run to compare the distribution of A + T + vs. A + T- profiles, regardless of N status, across MCI and dementia patients. Results: The most represented ATN profile in both groups was A + T + N + (MCI: 54%;dementia: 70.3%);3.4% of dementia patients and none within the MCI cohort presented with an A + T-N + profile. When grouping ATN profiles solely based on A and T dimensions, the prevalence of A + T + was of 76.3% and 66% in dementia and MCI patients, respectively. No association between clinical diagnoses (i.e., MCI vs. dementia status) and AT profiles (i.e., A + T + vs. A + T-) was detected. Discussion: The distribution of A + T + vs. A + T- does not differ between MCI and ADD, with A + T + profiles being predominant in both clinical categories. This does not support the common notion of A + T- profiles being relatively more prevalent in MCI patients, as indexing an earlier and/or less severe disease. Hence, caution should be exerted in attributing a case of MCI to prodromal AD solely based on A-positivity in the presence of a T-negative profile. © 2022, Fondazione Società Italiana di Neurologia.

关键词： Alzheimer’s disease Amyloid Cerebrospinal fluid Mild cognitive impairment Tau

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Human platelet lysate biotherapy for traumatic brain injury: preclinical assessment (vol 144, pg 142, 2021)

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BRAIN 2021年第10期144卷 E93-E93页

作者： Nebie, Ouada Carvalho, Kevin Barro, Lassina Delila, Liling Faivre, Emilie Renn, Ting-Yi Chou, Ming-Li Wu, Yu-Wen Nyam-Erdene, Ariunjargal Chou, Szu-Yi Buee, Luc Hu, Chaur-Jong Peng, Chih-Wei Devos, David Blum, David Burnouf, Thierry Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan University of Lille Inserm CHU Lille U1172 - LilNCog—Lille Neuroscience and Cognition Lille F-59000 France Alzheimer and Tauopathies LabEx DISTALZ LiCEND Lille F-59000 France International PhD Program in Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei 11031 Taiwan Institute of Clinical Medicine National Yang-Ming University Taipei Taiwan NeuroTMULille International Laboratory Taipei Medical University Taipei 11031 Taiwan PhD Program for Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University and National Health Research Institutes Taipei 11031 Taiwan Graduate Institute of Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan NeuroTMULille International Laboratory Univ. Lille Lille F-59000 France Dementia Center Department of Neurology Shuang Ho Hospital Taipei Medical University New Taipei City 23561 Taiwan Neurology School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan School of Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei 11031 Taiwan International PhD Program in Cell Therapy and Regeneration College of Medicine Taipei Medical University Taipei 11031 Taiwan Brain and Consciousness Research Centre Taipei Medical University Shuang Ho Hospital New Taipei City 23561 Taiwan

Traumatic brain injury (TBI) leads to major brain anatomopathological damages underlined by neuroinflammation, oxidative stress and progressive neurodegeneration, ultimately leading to motor and cognitive deterioration. The multiple pathological events resulting from TBI can be addressed not by a single therapeutic approach, but rather by a synergistic biotherapy capable of activating a complementary set of signalling pathways and providing synergistic neuroprotective, anti-inflammatory, antioxidative, and neurorestorative activities. Human platelet lysate might fulfil these requirements as it is composed of a plethora of biomolecules readily accessible as a TBI *** the present study, we tested the therapeutic potential of human platelet lysate usingin vitro and in vivomodels of TBI. We first prepared and characterized platelet lysate from clinical-grade human platelet concentrates. Platelets were pelletized, lysed by three freeze-thaw cycles, and centrifuged. The supernatant was purified by 56°C 30 min heat treatment and spun to obtain the heat-treated platelet pellet lysate that was characterized by ELISA and proteomic analyses. Two mouse models were used to investigate platelet lysate neuroprotective potential. The injury was induced by an in-house manual controlled scratching of the animals’ cortex or by controlled cortical impact injury. The platelet lysate treatment was performed by topical application of 60 µl in the lesioned area, followed by daily 60 µl intranasal administration from Day 1 to 6 *** lysate proteomics identified over 1000 proteins including growth factors, neurotrophins, and antioxidants. ELISA detected several neurotrophic and angiogenic factors at ∼1–50 ng/ml levels. We demonstrate, using two mouse models of TBI, that topical application and intranasal platelet lysate consistently improved mouse motor function in the beam and rotarod tests, mitigated cortical neuroinflammation, and oxidative stress in the injury a

关键词： human platelet lysate traumatic brain injury neuroprotection neurorestoration neurotrophins

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Fabrication of hyaluronic acid with graphene quantum dot as a dual drug delivery system for cancer therapy

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FlatChem 2024年 44卷

作者： Lin, Joseph Lin, Jung-Hua Yeh, Tseng-Yu Zheng, Jia-Huei Cho, Er-Chieh Lee, Kuen-Chan Department of Science Education National Taipei University of Education No.134 Sec. 2 Heping E. Rd. Da-an District Taipei City 106 Taiwan School of Pharmacy College of Pharmacy Taipei Medical University 250 Wuxing Street Taipei City 110 Taiwan Master Program in Clinical Genomics and Proteomics College of Pharmacy Taipei Medical University 250 Wuxing Street Taipei City 110 Taiwan Cancer Center Wan Fang Hospital Taipei Medical University 110 Taiwan PhD Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei City 110 Taiwan

With recent advancements in nanomedicine, there has been growing interest in developing drug delivery systems with multifunctional capabilities. In this study, we developed a novel dual drug delivery system by combining two drug carriers via positive and negative electrostatic interactions. First, we modified polyethyleneimine (PEI) with graphene quantum dots (GQDs) to create a positively charged particle (GPI) with high drug loading efficiency and good dispersibility. Second, we embedded the pyrenebutyric acid structure in hyaluronic acid (HA) through EDC/NHS cross-linking and used TAK-632 as the hydrophobic drug to create negatively charged particles (HANPs) with hydrogel-like properties and the CD44 receptor. After the two components were constructed, the increase in the particle charge and simultaneous delivery of both drugs synergistically enhanced the therapeutic effect of this strategy. Qualitative tests confirmed the successful synthesis of the drug carrier, while the potential of this system as a cancer treatment strategy was evaluated in HCT116 cancer cells (through MTT cell viability assays) and in vivo mice xenograft experiments. Our results demonstrated that the dual drug delivery system, HANPs(TAK)/GPI(DOX), had a significant inhibitory effect on the growth of cancer cells both in vitro and in vivo, suggesting that this system is a promising candidate for a new type of treatment. © 2024 Elsevier B.V.

关键词： Dual drug delivery system Electrostatic interaction Graphene quantum dots Hydrophobic drug

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CuO NWs boosted triboelectric microfluidic nanosensor functionalized by collagen-protein interactions for real-time platelet count monitoring

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Chemical Engineering Journal 2024年 490卷

作者： Lin, Jia-Cheng Kaswan, Kuldeep Chatterjee, Subhodeep Wu, Yu-Wen Kumar Sharma, Manish Ranjan, Ashok Roy Barman, Snigdha Lin, Yu-Zih Burnouf, Thierry Boireau, Wilfrid Lu, Ming-Yen Tu, Yong-Kwang Su, I-Chang Wu, Ping-Hsiu Lin, Zong-Hong Fan, Yu-Jui School of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Taipei Neuroscience Institute Taipei Medical University Taipei11031 Taiwan Department of Biomedical Engineering National Taiwan University Taipei11031 Taiwan International Intercollegiate PhD Program National Tsing Hua University Hsinchu30013 Taiwan Department of Power Mechanical Engineering National Tsing Hua University Hsinchu30013 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering Taipei Medical University Taipei11031 Taiwan Department of Material Science and Engineering National Tsing Hua University Hsinchu30013 Taiwan Institute of Biomedical Engineering National Tsing Hua University Hsinchu30013 Taiwan International PhD Program in Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Université de Franche-Comté CNRS Institut FEMTO-ST BesançonF-25030 France Department of Neurosurgery Shuang Ho Hospital Taipei Medical University New Taipei City23561 Taiwan Department of Surgery School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Department of Radiology School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Department of Radiation Oncology Taipei Medical University Hospital Taipei11031 Taiwan Center for Precision Health and Quantitative Sciences Taipei Medical University Hospital Taipei 11031 Taiwan

Blood platelet count significantly affects the development of severe conditions like myocardial infarction, peripheral arterial ischemia, respiratory compromise, stroke, diabetes, coronavirus disease 2019 (COVID-19), along with chemotherapy patients and those suffering cardiovascular diseases (CVDs). These conditions necessitate frequent monitoring of platelet counts to guide diagnostic and therapeutic decisions. However, existing techniques are relatively time-consuming, lack of accuracy and require precise operation. The emergence of these severe diseases underscored the need to develop advanced platelet count-monitoring techniques which are rapid, highly precise, and conveniently portable for point-of-care applications. In this study, we emphasized the development of a triboelectric microfluidic nanosensor (TMNS) for platelet quantification through the assessment of flow resistance. The functionality of TMNS device is based on immobilization of platelets on a collagen layer coated inside a microfluidic channel. The triboelectric voltage output is measured as a detection signal of the flow resistance and is enhanced by incorporating high surface area copper oxide nanowires (CuO NWs) on the interior of copper tubes. These copper tubes serve as terminal electrodes and for flow guiding. The flow resistance of plasma solutions is elevated when the platelet concentration increases due to heightened adherence of platelets onto the collagen layer. Variations in flow resistance induce alterations in contact electrification, causing changes in output voltage at load terminals. Fine-tuning of the TMNS device was achieved by optimizing the channel width and length, flowing liquid viscosity, and voltage measurement technique. Platelet quantification sensing data were acquired through the combination of platelet-rich plasma (PRP) and platelet-poor plasma (PPP) solutions. The described device exhibits promising capabilities for platelet-count monitoring in whole-blood samples c

关键词： Copper oxides

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Ludwigia octovalvis (Jacq.) P.H. Raven extract improves memory performance in mice with chronic kidney disease

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Phytomedicine Plus 2024年第2期4卷 100556-100556页

作者： Wang, Hao-Wei Huang, Yi-Hsuan Tung, Hsiao-Jou Lin, Wei-Sheng Chiu, Hao-Chieh Lin, Shuei-Liong Fan, Shou-Zen Wang, Pei-Yu Hsieh Yu Enterprise Co. Ltd. Taipei Taiwan Graduate Institute of Brain and Mind Sciences College of Medicine National Taiwan University Taipei Taiwan Department of Pediatrics Taipei Veterans General Hospital Taipei Taiwan Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine National Taiwan University Taipei Taiwan Graduate Institute of Physiology College of Medicine National Taiwan University Taipei Taiwan Department of Anesthesiology National Taiwan University Hospital National Taiwan University Taipei Taiwan Department of Anesthesiology En Chu Kong Hospital Taipei Taiwan Neurobiology and Cognitive Science Center National Taiwan University Taipei Taiwan PhD. Program in Translational Medicine National Taiwan University and Academia Sinica Taipei Taiwan PhD. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan

Background: Chronic kidney disease (CKD) is a significant global health concern often accompanied by cognitive impairment in affected patients. Ludwigia octovalvis extract (LOE) is a traditional medicine widely used for various conditions, including renal disease and its associated complications. However, the pharmacological effects and underlying mechanisms of LOE on CKD remain unclear. Methods: Adult male mice underwent a 4-week oral adenine-induced CKD model, followed by daily administration of either a vehicle, losartan, or LOE for 1 to 2 months. A battery of behavioral tests was conducted to examine CKD-associated cognitive impairments. Additionally, RNA sequencing, Golgi staining, and immunohistochemistry were performed to decipher the underlying mechanisms. Results: Neither losartan nor LOE supplementation could reverse adenine-induced kidney damage. However, during behavioral tests, both losartan and LOE treatments improved memory performance in mice without affecting emotional status and general locomotor activity. Transcriptome profiling and histological analyses revealed altered dendritic arborization and increased spine density of dentate granule cells, along with augmented adult hippocampal neurogenesis, contributing to the improved memory performance of mice treated with LOE. Conclusion: Our study provides comprehensive neurobehavioral and molecular evidence supporting the potential use of LOE for future CKD-associated memory dysfunction treatment. © 2024 The Author(s)

关键词： Adenine Cognitive dysfunction Neurogenesis

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