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Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis

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Neural Regeneration Research 2024年第10期19卷 2281-2289页

作者： Wang Liao Jiana Wei Chongxu Liu Haoyu Luo Yuting Ruan Yingren Mai Qun Yu Zhiyu Cao Jiaxin Xu Dong Zheng Zonghai Sheng Xianju Zhou Jun Liu department of neurology The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Special Medical Service Center Neuroscience CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangdongGuangdong ProvinceChina department of Rehabilitation The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of neurology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of neurology The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Biomedical and Health Engineering Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

关键词： Alzheimer's disease APP/PS1 double-transgenic Alzheimer's disease mouse model inflammation intestinal barrier dysfunction magnesium-L-threonate microbiome microbiota-gut-brain axis oxidative stress serum metabolites

Status of biomarker development for frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第10期19卷 2117-2118页

作者： Yue Yang Qi Cheng Jianqun Gao Woojin Scott Kim Brain and Mind centre&School of Medical Sciences The University of SydneySydneyNSWAustralia department of neurology and Neurophysiology Liverpool HospitalSydneyNSWAustralia Stroke and neurology Research Group Ingham Institute for Applied Medical ResearchSydneyNSWAustralia Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation ShanghaiChina clinical Research Center for Anesthesiology and Perioperative Medicine ShanghaiChina Translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina

Frontotemporal dementia(FTD) and amyotrophic lateral sclerosis(ALS) are neurodegenerative diseases that belong to the same disease spectrum,with overlapping of genetic and pathological *** mutations in TARDBP,C9ORF72,... 详细信息

关键词： amyotrophic sclerosis diseases

Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease

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Chinese Medical Journal 2024年第4期137卷 450-456页

作者： Yuwen Zhao Lixia Qin Hongxu Pan Tingwei Song Yige Wang Xiaoxia Zhou Yaqin Xiang Jinchen Li Zhenhua Liu Qiying Sun Jifeng Guo Xinxiang Yan Beisha Tang Qian Xu department of neurology Xiangya HospitalCentral South UniversityChangshaHunan 410008China department of neurology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Bioinformatics Center National clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China department of Geriatrics Xiangya HospitalCentral South UniversityChangshaHunan 410008China centre for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangshaHunan 410008China

Background:Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease(PD)risk factors;however,no comprehensive analyses of these genes in patients with PD have been ***,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with ***:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 ***,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 ***:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,***-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset ***,the significance did not pass the Bonferroni ***,72 and 1730 common variants were found in the WES and WGS cohorts,***,single-variant logistic association analyses did not identify significant associations between common variants and ***:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese ***,we highlight the complexity of PD and the need for extensive research elucidating its etiology.

关键词： Parkinson’s disease Transcription factors Dopaminergic neurons Genetic Variants

Safety and efficacy of a novel responsive neurostimulation system in China for drug-refractory focal epilepsy:The first-in-man study

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Chinese Medical Journal 2024年第12期137卷 1486-1488页

作者： Kailiang Wang Yongzhi Shan Penghu Wei Liankun Ren Liang Chen Junming Zhu Guoguang Zhao department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China International neuroscience Institute(China-INI) Clinical Research Center for EpilepsyCapital Medical UniversityBeijing 100053China China National Medical Center for Neurological Diseases Beijing 100053China department of neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China department of Neurosurgery Huashan HospitalFudan UniversityShanghai 200032China department of Neurosurgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang 310009China

To the Editor:Recent studies have characterized drugresistant epilepsy(DRE)as essentially a neural network disease.[1]Detection and disconnection of this pathological epileptic connectome or network can greatly improve seizure *** team also proposes the development of the newly emerging branch of epileptic networks neurosurgery(ENN).Responsive neurostimulation(RNS)is an ENN-oriented emerging treatment option without the resection of the seizure-onset zone or epileptic focus and aims to control the seizure or other epileptic manifestations by modulating or disrupting the network’s key nodes(epileptic hubs)in a self-responsive way.

关键词： epilepsy stimulation drug

Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

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Neural Regeneration Research 2025年第1期20卷 191-192页

作者： Narek Manukjan Daniel Fulton Zubair Ahmed WMatthijs Blankesteijn Sébastien Foulquier department of Pharmacology and Toxicology Maastricht UniversityMaastrichtThe Netherlands CARIM-School for Cardiovascular Diseases Maastricht UniversityMaastrichtThe Netherlands neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK centre for Trauma Sciences Research University of BirminghamEdgbastonBirminghamUK MHeNs-School for Mental Health and neuroscience Maastricht UniversityMaastrichtThe Netherlands department of neurology Maastricht University Medical CenterMaastrichtThe Netherlands

As the population ages,the burden of age-related diseases becomes ***,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common ***,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of *** term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).

关键词： pathology becoming white

Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS): protocol of a prospective, multicentre, randomised, controlled trial

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Stroke & Vascular neurology 2024年第1期9卷 66-74页

作者： Xuan Sun Ming Yang Dapeng Sun Guangge Peng Yiming Deng Xingquan Zhao Liping Liu Ning Ma Feng Gao Dapeng Mo Wengui Yu Yongjun Wang Yilong Wang Zhongrong Miao department of Interventional Neuroradiology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of neurology Beijing Luhe HospitalCapital Medical UniversityBeijingChina department of neurology Comprehensive Stroke&Cerebrovascular CenterUniversity of California IrvineIrvineCaliforniaUSA Chinese Institute for Brain Research BeijingChina National Center for Neurological Diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina China National clinical Research Center for Neurological Diseases BeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina

Background The superiority of balloon angioplasty plus aggressive medical management(AMM)to AMM alone for symptomatic intracranial artery stenosis(sICAS)on efficacy and safety profiles still lacks evidence from randomised controlled trials(RCTs).Aim To demonstrate the design of an RCT on balloon angioplasty plus AMM for *** Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis(BASIS)trial is a multicentre,prospective,randomised,open-label,blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with *** eligible in BASIS were 35–80 years old,with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis(70%–99%)of a major intracranial *** eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 *** groups will receive identical AMM,including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy,intensive risk factor management and life-style *** participants will be followed up for *** outcomes Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up,or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment,is the primary *** BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients,which may provide an alternative perspective for treating *** registration number NCT03703635;https://***.

关键词： balloon prospective centre

Magnetic resonance spectroscopy findings of brain olfactory areas in patients with COVID-19-related anosmia:A preliminary comparative study

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 105-112页

作者： Shadman Nemati Mohammad Haghani Dogahe Alia Saberi Naghi Ramezani Pejman Kiani Tofigh Yaghubi Kalurazi Ehsan Kazemnejad Leili Sara Seddighi Abbas Monsef department of Otolaryngology and Head and Neck Surgery School of MedicineOtorhinolaryngology Research CenterGuilan University of Medical SciencesRashtIran Guilan Road Trauma Research Center Guilan University of Medical SciencesRashtGuilanIran department of neurology Neuroscience Research CenterPoursina HospitalGuilan University of Medical SciencesRashtIran department of Radiology Pars International HospitalGuilan ProvinceIran department of neuroscience and Addiction Studies School of Advanced Technologies in MedicineTehranIran department of Infectious Diseases Razi Clinical Research Development UnitRazi HospitalGuilan University of Medical SciencesRashtIran Center of Magnetic Resonance Research Department of Radiation OncologyUniversity of Minnesota Medical SchoolMinneapolisMinnesotaUSA

Objectives:2019 novel coronavirus disease(COVID-19)infection is commonly associated with olfactory dysfunctions,but the basic pathogenesis of these complications remains *** study seeks to evaluate the value of magnetic resonance spectroscopy(MRS)in determining the molecular neurometabolite alterations within the main brain olfactory areas in patients with COVID-19-related ***:In a cross-sectional study,seven patients with persistent COVID-19-related anosmia(mean age:29.57 years)and seven healthy volunteers(mean age:27.28 years)underwent MRS in which N-acetyl-aspartate(NAA),choline(Cho),creatine(Cr),and their ratios were measured in the anterior cingulate cortex,dorsolateral prefrontal cortex,orbitofrontal cortex(OFC),insular cortex,and ventromedial prefrontal *** were analyzed using TARQUIN software(version 4.3.10),and the results were compared with an independent sample t-test and nonparametric Mann-Whitney test based on the normality of the MRS data ***:The mean duration of anosmia before imaging was 8.5 months in COVID-19-related anosmia *** analysis elucidated a significant association between MRS findings within OFC and COVID-19-related anosmia(P_(disease)<0.01),and NAA was among the most important neurometabolites(P_(interaction)=0.006).Reduced levels of NAA(P<0.001),Cr(P<0.001)and^(NAA)/Cho ratio(P=0.007)within OFC characterize COVID-19-related ***:This study emphasizes that MRS can be illuminating in COVID-19-related anosmia and indicates a possible association between central nervous system impairment and persistent COVID-19-related anosmia.

关键词： anosmia COVID-19 magnetic resonance spectroscopy neuroimaging olfaction

Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

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Journal of Integrative Medicine 2024年第1期22卷 46-53页

作者： Rosemary Arnold Jenifer Murphy-Smith Chee H.Ng David Mischoulon Gerard J.Byrne Chad A.Bousman Con Stough Michael Berk Jerome Sarris Professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia Depression clinical and Research Program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of Medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada department of Psychiatry the University of MelbourneMelbourne 3052Australia centre for Human Psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and Physical Health and clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The centre of Excellence in Youth Mental Health the University of MelbourneParkville 3052Australia Florey Institute of neuroscience and Mental Health the University of MelbourneParkville 3052Australia NICM Health Research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg Depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial Placebo Depression Nutraceutical Psychiatry

High-throughput discovery of highly selective reversible hMAO-B inhibitors based on at-line nanofractionation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1772-1786页

作者： Yu Fan Jincai Wang Jingyi Jian Yalei Wen Jiahao Li Hao Tian Jacques Crommen Wei Bi Tingting Zhang Zhengjin Jiang Institute of Pharmaceutical Analysis/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China/College of Pharmacy Jinan UniversityGuangzhou 510632China KU Leuven-University of Leuven Pharmaceutical AnalysisDepartment of Pharmaceutical and Pharmacological SciencesLeuven 3000Belgium Laboratory of Analytical Pharmaceutical Chemistry Department of Pharmaceutical SciencesCIRMUniversity of LiegeLiege B-4000Belgium department of neurology the First Affiliated Hospital of Jinan University/Clinical Neuroscience Institutethe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China

Human monoamine oxidase B(hMAO-B)has emerged as a pivotal therapeutic target for Parkinson's *** to adverse effects and shortage of commercial drugs,there is a need for novel,highly selective,and reversible hMAO-B inhibitors with good blood-brain barrier *** this study,a high-throughput at-line nanofractionation screening platform was established with extracts from Chuanxiong Rhizoma,which resulted in the discovery of 75 active compounds,including phenolic acids,volatile oils,and phthalides,two of which were highly selective novel natural phthalide hMAO-B inhibitors that were potent,selective,reversible and had good blood‒brain *** docking and molecular dynamics simulations elucidated the inhibition ***(IC_(50)=103 nmol/L;SI=645)and neocnidilide(IC_(50)=131 nmol/L;SI=207)demonstrated their excellent potential as hMAO-B *** offset the limitations of deactivating enzymes associated with irreversible hMAO-B inhibitors such as *** SH-SY5Y cell assays,sedanolide(EC_(50)=0.962μmol/L)and neocnidilide(EC_(50)=1.161μmol/L)exhibited significant neuroprotective effects,comparable to the positive drugs rasagiline(EC_(50)=0.896μmol/L)and safinamide(EC_(50)=1.079μmol/L).These findings underscore the potential of sedanolide as a novel natural hMAO-B inhibitor that warrants further development as a promising drug candidate.

关键词： Human monoamine oxidase B inhibitors High-throughput screening At-linenanofractionation Parkinson's disease Cellular neuroprotection Traditional Chinese medicines(TCMs)