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Confirmation of the Experimentally-Proven Therapeutic Utility of Madecassoside in an Aβ<sub>1-42</sub>Infusion Rat Model of Alzheimer’s Disease by in Silico Analyses

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Advances in Alzheimer's Disease 2015年第2期4卷 37-44页

作者： Abdullah Al Mamun Michio Hashimoto Shahdat Hossain Masanori Katakura Hiroyuki Arai Osamu Shido Department of Environmental Physiology Shimane University Faculty of Medicine Izumoshi Japan Laboratory of Alternative Medicine and Behavioral neurosciences Department of Biochemistry and Molecular Biology Jahangirnagar University Dhaka Bangladesh Department of Geriatrics and Gerontology Division of Brain Sciences Institute of Development Aging and Cancer Tohoku University Sendai Japan

The accumulation of amyloid β peptide 1 - 42 (Aβ1-42) in the brain of Alzheimer’s disease (AD) patients is known to be associated with neurodegeneration and memory impairment. More recently, we reported that madecassoside, an active component of Centella asiatica, improved memory impairment in an Aβ1-42 infusion rat model of AD, ameliorated neurotoxicity in SH-SY5Y cells, and inhibited in vitro Aβ1-42 fibril formation. In the present study, we investigated the utility of in silico analyses in corroborating observed in vivo and in vitro effects of madecassoside in AD to further assess the therapeutic benefits of madecassoside. The 3D structure of Aβ1-42 was downloaded from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB). The binding of madecassoside to Aβ1-42 was assessed by molecular docking. The chemical structure of madecassoside was modeled and converted to the PDB format. Madecassoside was found to successfully dock with Aβ1-42. Computational demonstration of the binding of madecassoside to Aβ1-42 further corroborated the inhibitory effect of madecassoside on Aβ1-42 fibrillogenesis which was demonstrated in our previous study. These data showed the potential utility of madecassoside as a preventive medication in Aβ1-42-induced neurodegenerative diseases such as AD.

关键词： Alzheimer’s Disease Centella asiatica Madecassoside Ayurveda in Silico Drug Designing

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Esthesioneuroblastoma Masquerading as Chronic Rhinosinusitis

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Case Reports in Clinical Medicine 2015年第9期4卷 303-308页

作者： Sylvia G. McCulloch Harold Y. Lau Yves Starreveld John T. Lysack Desiree Hao Department of Internal Medicine Faculty of Medicine University of Calgary Calgary Canada Tom Baker Cancer Center/University of Calgary Calgary Canada division of Neurosurgery Foothills Medical Centre Calgary Canada Clinical neurosciences and Surgery University of Calgary Department of Diagnostic Imaging Foothills Medical Centre Calgary Canada

Background: Esthesioneuroblastoma, a rare tumour of the nasal vault, can present with symptoms that can be mistaken for common conditions such as chronic rhinosinusitis or recurrent epistaxis. Case presentation: A 52-year-old, previously healthy, Caucasian female presented to the emergency room with two months of nasal congestion and a spontaneous, protracted nosebleed that required a nasal clamp to settle. In the following months she had another episode of epistaxis in addition to fatigue, headaches, anosmia, difficulty breathing, worsening vision, weight loss and behavioral changes. Subsequent investigations led to the diagnosis of esthesioneuroblastoma. Conclusion: When patients present with recurrent epistaxis or chronic rhinosinusitis that does not respond to a reasonable course of medical therapy and/or have atypical associated symptoms, further investigations should be considered. The presences of red flags, such as weight loss, severe headaches, vision changes or bizarre behavior are also clues that alternate diagnoses and further additional workup should be considered.

关键词： Esthesioneuroblastoma Sinonasal Neoplasms Sinusitis Epistaxis

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晶体超声乳化术后隐匿性前房金属碎片易被误诊为慢性难治性术后炎症反应

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世界核心医学期刊文摘（眼科学分册） 2005年第8期1卷 29-30页

作者： Stangos A.N. Pournaras C.J. Petropoulos I.K. 刘玮 division of Op hthalmology Department of Clinical Neurosciences University Hospitals of Genev a 22 Alcide-Jentzer 1211 Geneva Switzerland Dr.

PURPOSE: To report a case of an occult, metallic, anterior-chamber intraocula r foreign body after uneventful phacoemulsification that was masquerading as chr onic recalcitrant postoperative inflammation. DESIGN: Interventional case report . METHODS: A 73-year-old patient was referred to us for recalcitrant anterior -chamber inflammation after uneventful phacoemulsification; the patient present ed with visual disturbances, anterior-chamber inflammation, and macular epireti nal membrane with concomitant cystoid macular edema. RESULTS: After meticulous e valuations and repeated clinical examinations, a metallic intraocular foreign bo dy was discovered on the iris, which was surgically removed and analyzed. Chemic al analysis revealed copper, aluminum, and zinc. Pars plana vitrectomy with epir etinal membrane and indocyaninegreen-assisted internal limiting membrane peelin g followed, with subsequent improvement of visual acuity. CONCLUSIONS: Intraocul ar foreign bodies should always be considered in the differential diagnosis of r ecalcitrant inflammation postphacoemulsification. However, in the absence of int raocular inflammation, surgical removal of such particles is questionable.

关键词：超声乳化术术后炎症反应隐匿性玻璃体切除术内界膜睫状体平坦部黄斑视网膜前膜黄斑囊样水肿眼内异物干预性

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Pott puffy tumor in an unusual location

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Open Journal of Pediatrics 2013年第2期3卷 147-150页

作者： Richard H. Schwartz Carla Zingariello Rebecca Levorson John S. Myseros Riva Kamat Theodore W. Fetter Department of neurosciences Division of Neurosurgery Children’s National Medical Center Washington DC USA Department of Pediatrics Inova Fairfax Hospital for Children Falls Church USA Department of Surgery Section of Otolaryngology—Head-Neck Surgery Inova Fairfax Hospital for Children Falls Church USA

Pott puffy tumor is almost always associated with an outward extension of suppurative acute frontal sinusitis. Pathogenesis includes osteomyelitis of the frontal bone with local spread of the infection to the outer cortex and termination of the suppurative process in a frontal subgaleal abscess. An unusual ectopic location of Pott puffy tumor is the tempo-parietal subgaleal space, located exterior to the squamous portion of the temporal bone. In this location, Pott puffy tumor is considered a suppurative complication of otomastoiditis. Reported here is a 4-year-old boy who developed amoxicillin-resistant acute otitis media, silent mastoiditis, temporal bone subperiosteal abscess, subgaleal abscess, and an epidural abscess. He had several fenestra of the tegmen mastoideum as a result of osteiitis of the temporal bone, which we believe permitted spread of the oto-mastoiditis to temporal bone, subgaleal space, and epidural space. Surgical specimens obtained from the middle ear and subgaleal abscess after 24-hours of intravenously-administered combination antibiotic therapy did not reveal any aerobic or anaerobic bacterial pathogens. This is only the second such pediatric case that we found during a careful search of the literature.

关键词： Pott Puffy Tumor Epidural Abscess Subgaleal Abscess

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Impact of Motor Speech Intervention on Neural Activity in Children with Speech Sound Disorders: Use of Magnetoencephalography

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Journal of Behavioral and Brain Science 2018年第7期8卷 415-429页

作者： Vickie Y. Yu Darren S. Kadis Debra Goshulak Aravind K. Namasivayam Margit Pukonen Robert M. Kroll Luc F. De Nil Elizabeth W. Pang Department of Communication Disorders and Sciences California State University Northridge California USA division of Neurology and Pediatric Neuroimaging Research Consortium Cincinnati Children’s Hospital Medical Center Cincinnati USA The Speech & Stuttering Institute Toronto Canada Department of Speech-Language Pathology University of Toronto Toronto Canada neurosciences and Mental Health Sick Kids Research Institute Toronto Canada division of Neurology Hospital for Sick Children Toronto Canada

We present the novel use of a neuroimaging technique, magnetoenceph-alography (MEG), for examining therapy-related changes in neural activity during a speech and a non-speech motor task in children with speech sound disorders (SSD). Nine children (mean age = 4.2 years) with SSD were scanned in the MEG before and after an eight-week course of intensive motor speech therapy. MEG tasks involved an oromotor and a syllable production task. MEG analyses identified significant post-therapy changes in brain regions related to oromotor control and speech production. Behavioral assessments showed significant improvements on measures of motor speech skills and articulation following intervention. This is the first demonstration of the ability of MEG to: 1) capture brain activations resulting from oromotor movements and simple syllable production in young children, and 2) capture brain changes related to speech therapy. As the findings from this study are promising, we discuss directions for the design of future studies to further examine specific neural dysfunctions in speech sound disorders.

关键词： Speech Sound Disorders Children Intervention Neuroimaging Speech Production

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Hub analysis of directed brain networks in AD and MCI

Hub analysis of directed brain networks in AD and MCI

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中国神经科学学会第十二届全国学术会议

作者： Ali Khazaee Abbas Babajani-Feremi Departrment of Electrical Engineering University of Bojnord Department of Pediatrics Division of Clinical Neurosciences University of Tennessee Health Science Center Neuroscience Institute Le Bonheur Children's Hospital Department of Anatomy and Neurobiology University of Tennessee Health Science Center

Objective We presented a method of hub analysis for identification of alterations in the brain networks of patients with mild cognitive impairment（MCI） and Alzheimer’s disease（AD）. Hub nodes in the brain are important regions that play a central role in overall organization of the brain network. Reorganization of the brain networks in patients with MCI and AD may eliminate or add some hub nodes to the network. Our method was based on Granger causality（GC） analysis of resting-state functional magnetic resonance imaging（rs-f MRI） data. 34 patients with AD, 89 patients with MCI, and 45 age-matched healthy controls（HC） from the Alzheimer’s disease neuroimaging initiative（ADNI） database were included in this study. We used the GC approach to define a directed graph of the brain network. Methods Nodes with a degree of two standard deviation higher than the mean of degree of all nodes were identified as hub nodes. Since the graph measures are threshold-dependent, we calculated the degree of nodes by varying the threshold in a range from 0.1 to 0.3 with a step of 0.01. For each value of threshold, the degree of nodes was calculated, and then hub nodes were identified. At the end of analysis, percentage of identification of a node as a hub node in different threshold values was calculated. Results Some hub nodes are common between three groups which correspond to right parahippocampal gyrus, right insular cortex, left precuneus, left thalamus, and right precuneus. More importantly, some hub nodes are present only in HC group and they are missing in AD or MCI groups. These hub nodes are within the left parahippocampal gyrus and right inferior temporal gyrus. There are also some regions that were hub nodes in MCI and AD but not in HC. These regions were within the right calcarine fissure and right inferior parietal gyrus. Conclusion Hub nodes are different in HC, MCI, and AD.

关键词： AD MCI rs-fMRI Graph theory

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Antenatal use of bosentan and/or sildenafil attenuates pulmonary features in rats with congenital diaphragmatic hernia

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World Journal of Pediatrics 2014年第4期10卷 354-359页

作者： María de Lourdes Lemus-Varela Amed Soliz Belinda Claudia Gómez-Meda Ana Lourdes Zamora-Perez José Manuel Ornelas-Aguirre Valery Melnikov Blanca Miriam Torres-Mendoza Guillermo Moisés Zúñiga-González division of Neonatology High Specialty Medical UnitPediatric HospitalWestern National Medical CenterMexican Social Security InstituteGuadalajaraJaliscoMéxico Neonatal Intensive Care Unit Division of NeonatologyMiami Children's HospitalMiami FLDUSA Molecular Biology in Medicine Institute Molecular Biology and Genomic DepartmentHealth Sciences University CenterUniversity of GuadalajaraGuadalajaraJaliscoMéxico Odontology Research Institute Integrated Odontology Clinic DepartmentHealth Sciences University CenterUniversity of GuadalajaraGuadalajaraJaliscoMéxico Pathology Department High Specialty Medical UnitNorth-western National Medical CenterMexican Social Security InstituteCiudad ObregónSonoraMéxico School of Medicine University of ColimaColimaMéxico division of neurosciences Western Biomedical Research CenterMexican Social Security Institute and Department of ClinicsHealth Sciences University CenterUniversity of GuadalajaraGuadalajaraJaliscoMéxico Mutagenesis Laboratory Western Biomedical Research CenterMexican Social Security InstituteGuadalajaraJaliscoMéxico

Background:Lung hypoplasia,pulmonary persistent hypertension of the newborn and its morphological changes are the main features in congenital diaphragmatic hernia(CDH).This study was undertaken to investigate if antenatal use of sildenafil and/or bosentan attenuates vascular remodeling,promotes branching,and improves alveolarization in experimental nitrofeninduced ***:Nitrofen(100 mg)was gavage-fed to pregnant rats at post conception day(PCD)9 to induce *** rats were randomized to 5 groups:1)control;2)nitrofen;3)nitrofen+sildenafil 100 mg/kg per day at PCD 16-20;4)nitrofen+bosentan 30 mg/kg per day,at PCD 16-20,and 5)nitrofen+bosentan+sildenafil,same doses and administration *** cesarean delivery,the offsprings were sacrifi *** diaphragmatic defect and pulmonary hypoplasia were identified,and the lungs were *** wall thickness,bronchiolar density and alveolarization were ***:The offsprings with CDH were characterized by severe pulmonary hypoplasia(lung weight-to-body weight ratio:0.0263[95%confidence interval(CI)0.0242-0.0278)]in the nitrofen group versus 0.0385(95%CI 0.0355-0.0424)in the control group(P=0.0001).Pulmonary arterial wall thickness was decreased to 3.0(95%CI 2.8-3.7)μm in the nitrofen+sildenafil group versus 5.0(95%CI 4.1-4.9)μm in the nitrofen group(P=0.02).Terminal bronchioles increased to 13.7(95%CI 10.7-15.2)μm in the nitrofen+bosentan group in contrast to 8.7(95%CI 7.2-9.4)μm in the nitrofen group(P=0.002).More significant differences(P=0.0001)were seen in terminal bronchioles in the nitrofen+sildenafil+bosentan group than in the nitrofen group[14.0(95%CI 12.5-15.4)μm versus 8.5(95%CI 7.1-9.3)μm].Pulmonary arterial wall thickness was also decreased in the former ***:In this rat model,antenatal treatment with sildenafil attenuates vascular *** promotes the development of terminal bronchioles in nitrofen-induced CDH.

关键词： antenatal treatment bosentan congenital diaphragmatic hernia pulmonary hypoplasia sildenafil

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Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease

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Translational Neurodegeneration 2021年第2期10卷 230-239页

作者： Mari Aksnes Hans Christian DAass Ann Tiiman Trine Holt Edwin Lars Terenius Nenad Bogdanovic Vladana Vukojevic Anne-Brita Knapskog Department of Geriatric Medicine Institute of Clinical MedicineFaculty of MedicineUniversity of OsloOsloNorway Department of Medical Biochemistry Oslo University HospitalOsloNorway Department of Clinical neurosciences(CNS) Center for Molecular Medicine CMM L8:01Karolinska InstitutetStockholmSweden Department of Geriatric Medicine The Memory ClinicOslo University HospitalOsloNorway Institute of Health and Society Faculty of MedicineUniversity of OsloOsloNorway Norwegian National Advisory Unit on Ageing and Health Vestfold Hospital TrustTonsbergNorway Department of Neurobiology Care Science and Society(NVS)Division of Clinical GeriatricsKarolinska InstitutetHuddingeSweden

Background:The aggregation of amyloidβ(Aβ)is central in the pathogenesis of Alzheimer’s disease(AD).Recently it has been shown that specifically,larger,Thioflavin T-binding Aβaggregates are associated with increased neuroinflammation and cytokine *** study was aimed to quantify fibrillary amyloid aggregates,so-called nanoplaques,and investigate their relationship with cytokines in the cerebrospinal fluid(CSF).Methods:CSF was collected from 111 patients assessed for cognitive complaints at the Oslo University Hospital Memory *** patients were grouped based on their amyloid *** CSF nanoplaque concentration was quantified with the Thioflavin T-fluorescence correlation spectroscopy(ThT-FCS)*** levels of nine cytokines(eotaxin-1,granulocyte stimulating factor,interleukin[IL]-6,IL-7,IL-8,monocyte chemoattractant protein-1,gammainduced protein 10,macrophage inflammatory protein[MIP]-1α,and MIP-1β)were quantified with a magnetic bead-based multiplex assay and read on a Luminex IS 200 ***:There were 49 amyloid-negative and 62 amyloid-positive patients in the cohort;none of the cytokines differed significantly between the amyloid *** increased nanoplaque levels were associated with levels of MIP-1βbelow the lower limit of quantification,and with decreased levels of MIP-1αand *** associations remained significant when adjusted for age,sex,cognitive function,apolipoproteinε4 status and CSF core biomarker ***:The cytokine levels were not associated with amyloid status in this *** nanoplaque levels were negatively associated with MIP-1β,MIP-1αand IL-8,which is in line with recent findings suggesting that the upregulation of some cytokine markers has a protective role and is negatively associated with AD progression.

关键词： Alzheimer's disease Amyloid Amyloid beta peptides Amyloidogenic proteins Biomarkers Cerebrospinal fluid Cytokines Inflammation Fluorescence correlation spectroscopy Thioflavin T

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Long-Term Monoacylglycerol Lipase Inhibitor Treatment Decelerates Pathological Changes in APP/PS1-21 Mice, but Behavioral Improvements Require Early-Stage Treatment Onset—Short Report

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World Journal of Neuroscience 2018年第2期8卷 157-170页

作者： Rea Pihlaja Noora Lindgren Annamari Torittu Anniina Snellman Merja Haaparanta-Solin Juha O. Rinne PET Preclinical Laboratory Turku PET Centre University of Turku Turku Finland Medicity Research Laboratory University of Turku Turku Finland Turku PET Centre Turku University Hospital Turku Finland Department of Biochemistry University of Turku Turku Finland division of Clinical neurosciences Turku University Hospital Turku Finland

The arachidonic acid (AA) pathway produces several essential proinflammatory eicosanoids. However, in many neurodegenerative diseases, e.g. Alzheimer’s disease (AD), this pathway is chronically hyperactivated. In brain, primarily monoacylglycerol lipase (MAGL) hydrolyzes the endocannabinoid 2-arachidonoylglycerol to AA, which is further metabolized to generate many proinflammatory eicosanoids. MAGL inhibition, simultaneously reducing the level of eicosanoids and increasing those of neuroprotective endocannabinoids, has proved efficacious in some AD models, reducing neurotoxic β-amyloid (Aβ) levels and improving memory functions. Here, a MAGL inhibitor, JZL184 was chronically administered (16 mg/kg, i.p., 3 x/wk for 5 mo) for 1 - 1.5 mo and 7 - 8 mo old transgenic (TG) and wild-type (WT) APP/PS1-21 mice modelling cerebral amyloidosis. According to immunohistochemistry, JZL184 significantly increased the expression levels of cannabinoid receptor 1 in older WT and younger TG and WT mice, decreased cannabinoid receptor 2 and oligomeric Aβ in older and younger TG mice and decreased microglia-specific marker Iba1 in younger TG mice, compared to TG mice treated with vehicle only. However, in the Morris Water Maze test, spatial memory functions improved significantly only in younger TG and WT mice, compared to vehicle-treated littermates. These tentative results suggest that chronic, rather long-term MAGL inhibition can decelerate pathological changes in TG APP/PS1-21 mice but it improves memory functions only when administered at an early stage of the

关键词： Alzheimer’s Disease Arachidonic Acid Pathway Cannabinoid Receptor Monoacylglycerol Lipase Neuroinflammation

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Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy

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Cellular & Molecular Immunology 2021年第6期18卷 1353-1374页

作者： M.J.Mansilla S.Presas-Rodríguez A.Teniente-Serra I.González-Larreategui B.Quirant-Sánchez F.Fondelli N.Djedovic D.Iwaszkiewicz-Grześ K.Chwojnicki D.Miljković PTrzonkowski C.Ramo-Tello E.M.Martínez-Cáceres division of Immunology LCMNGermans Trias i Pujol University Hospital and Research InstituteBarcelonaSpain Department of Cellular Biology Physiology and ImmunologyUniversitat Autònoma de BarcelonaBellaterraSpain Multiple Sclerosis Unit Department of NeurosciencesGermans Trias i Pujol University HospitalBarcelonaSpain Department of Medicine Universitat Autònoma de BarcelonaBellaterraSpain View author publications Department of Immunology Institute for Biological Research“Siniša Stanković”-National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia Department of Medical Immunology Medical University of GdańskGdańskPoland Poltreg S.A. GdańskPoland Department of Anaesthesiology&Intensive Care Medical University of GdańskGdańskPoland

Multiple sclerosis(MS)is a leading cause of chronic neurological disability in young to middle-aged adults,affecting~2.5 million people ***,most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs,but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse ***,there is an urgent need for the development of next-generation treatments that,alone or in combination,stop the undesired autoimmune response and contribute to the restoration of *** review analyzes current MS treatments as well as different cell-based therapies that have been proposed to restore homeostasis in MS patients(tolerogenic dendritic cells,regulatory T cells,mesenchymal stem cells,and vaccination with T cells).Data collected from preclinical studies performed in the experimental autoimmune encephalomyelitis(EAE)model of MS in animals,in vitro cultures of cells from MS patients and the initial results of phase I/II clinical trials are analyzed to better understand which parameters are relevant for obtaining an efficient cell-based therapy for MS.

关键词： multiple sclerosis cell-based therapy tolerance neuroprotection autoimmunity

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