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Perspectives for delivery of therapeutics by extravasation of biodegradable microspheres in the brain

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Neural Regeneration Research 2024年第5期19卷 969-970页

作者： Anne-Eva van der Wijk Ed VanBavel Amsterdam UMC location University of Amsterdam Department of Biomedical Engineering and PhysicsAmsterdamThe Netherlands Amsterdam Neuroscience Neurovascular Disorders ProgramAmsterdamThe Netherlands Amsterdam Cardiovascular Sciences Microcirculation ProgramAmsterdamThe Netherlands

Development of therapeutics for brain diseases has remained challenging,in particular due to the difficulty of passing the blood-brain *** a result,the current arsenal of therapeutics targeting the brain is limited to small,lipid-soluble drugs and there is a lack of options for treating neuroblastomas,Alzheimer’s disease,and many other devastating *** the advances in strategies for crossing the blood-brain barrier such as the use of nanoparticles(Hersh et al.,2022;Duan et al.,2023),such delivery systems have not yet reached clinical ***,novel platforms for the transport of therapeutics across the blood-brain barrier remain highly *** specifically holds for large molecules such as monoclonal antibodies and recombinant proteins,as well as nucleotide-based therapeutics and cell *** efforts in this field are increasing exponentially,with thousands of publications in the last few years.

关键词： therapeutics holds spite

Modifying the progression of Parkinson's disease through movement interventions:multimodal quantification of underlying mechanisms

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Neural Regeneration Research 2024年第8期19卷 1651-1652页

作者： Manuel Bange Damian Marc Herz Dumitru Ciolac Gabriel Gonzalez-Escamilla Sergiu Groppa Section of Movement disorders and Neurostimulation Department of NeurologyFocus Program Translational Neuroscience(FTN)University Medical Center of the Johannes Gutenberg-University MainzMainzGermany

Introduction:Parkinson’s disease(PD)is the most common neurodegenerative movement *** pathological hallmark is the progressive loss of dopaminergic neurons of the substantia nigra pars compacta,which is accompanied by widespread alterations in the structu re and function of distributed brain *** r,these processes cause a variety of motor symptoms such as bradykinesia,rigidity,tremor,gait disorders,or difficulties in fine motor control(Bange et al.,2022).

关键词： alterations movement

Translating Pathological Brain Activity Primers in Parkinson’s Disease Research

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Research 2024年第1期2023卷 735-752页

作者： Daniela Mirzac Svenja L.Kreis Heiko J.Luhmann Gabriel Gonzalez-Escamilla Sergiu Groppa Movement disorders and Neurostimulation Department of NeurologyFocus Program Translational NeuroscienceRhine Main Neuroscience NetworkUniversity Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany Institute of Physiology University Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany

Translational experimental approaches that help us better trace Parkinson’s disease(PD)pathophysiological mechanisms leading to new therapeutic targets are urgently *** this article,we review recent experimental and clinical studies addressing abnormal neuronal activity and pathological network oscillations,as well as their underlying mechanisms and *** aim is to enhance our knowledge about the progression of Parkinson's disease pathology and the timing of its symptom’s ***,we present mechanistic insights relevant for the generation of aberrant oscillatory activity within the cortico-basal ganglia *** summarize recent achievements extrapolated from available PD animal models,discuss their advantages and limitations,debate on their differential applicability,and suggest approaches for transferring knowledge on disease pathology into future research and clinical applications.

关键词： clinical knowledge insight

The roles of RACK1 in the pathogenesis of Alzheimer's disease

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Journal of Biomedical Research 2024年第2期38卷 137-148页

作者： Wenting He Xiuyu Shi Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Child Neurodevelopment and Cognitive DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China

The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative ***1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of ***,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C ***,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal ***1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 *** potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential *** this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.

关键词： RACK1 Alzheimer's disease PKC amyloid-β synaptic plasticity neuroinflammation

Single-cell RNA sequencing in juvenile idiopathic arthritis

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Genes & Diseases 2024年第2期11卷 633-644页

作者： Xiwen Luo Xuemei Tang Department of Rheumatology and Immunology Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Key Laboratory of Child Infection and Immunity Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China

Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory rheumatic diseases in children,with onset before age 16 and lasting for more than 6 *** is a highly heterogeneous condition with various consequences for health and quality of *** some JIA patients,early detection and intervention remain *** a result,further investigation of the complex and unknown mechanisms underlying JIA is *** in technology now allow us to describe the biological heterogeneity and function of individual cell populations in *** this review,we hope to provide novel ideas and potential targets for the diagnosis and treatment of JIA by summarizing the current findings of single-cell RNA sequencing studies and understanding how the major cell subsets drive JIA pathogenesis.

关键词： Juvenile idiopathic arthritis Macrophage Macrophage activation syndrome Monocyte Single-cell RNA sequencing Synoviocyte T cell

Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia

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World Journal of Psychiatry 2024年第5期14卷 695-703页

作者： Wen-Peng Hou Xiang-Qin Qin Wei-Wei Hou Yun-Yi Han Qi-Jing Bo Fang Dong Fu-Chun Zhou Xian-Bin Li Chuan-Yue Wang Beijing Key Laboratory of Mental disorders National Clinical Research Center for Mental Disorders&National Center for Mental DisordersBeijing Anding HospitalCapital Medical UniversityBeijing 100088China Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijing 100069China

BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in ***,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still *** To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met *** In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative *** was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence *** COMT Met-carriers exhibited fewer negative symptoms than Val *** the total sample,significant negative correlations were found between negative symptoms and information,*** between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

关键词： Catechol-O-methyltransferase Val/Met polymorphism Cognitive reserve Crystallized intelligence Negative symptoms Schizophrenia

The immune system:uncharted pathways between senses and the brain

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Neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares Mar Cuadrado-Tejedor Ana García-Osta Juan JoséLasarte Immunology and Immunotherapy program Centre for Applied Medical Research(CIMA)University of NavarraIDISNAPamplonaSpain Division of Gene Therapy for Neurological disorders Centre for Applied Medical Research(CIMA)University of NavarraIDISNAPamplonaSpain Pathology Anatomy and Physiology DepartmentSchool of MedicineUniversity of NavarraIDISNAPamplonaSpain

Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth *** perception of external signals through the senses is essential to an organism's survival,transmitting signals to the central nervous system(CNS)and prompting physiological changes in other biological *** addition to the direct effects of sense-induced mediators in the brain.

关键词： prompt system transmitting

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

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Neural Regeneration Research 2024年第9期19卷 2036-2040页

作者： Xiaoyue Li Tao Liu Xuan Mo Runhua Wang Xueyan Kong Robin Shao Roger S.Mclntyre Kwok-Fai So Kangguang Lin Department of Affective disorders The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Psychiatry The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina mood disorders Psychopharmacology Unit Poul Hansen Family Centre for DepressionUniversity Health NetworkTorontoONCanada Department of Psychiatry University of TorontoTorontoONCanada Brain and Cognition Discovery Foundation TorontoCanada Ministry of Education Joint International Research Laboratory of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory ***,anti-inflammatory treatment has shown partial effectiveness in alleviating depression *** barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory *** our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold *** is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory *** the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo *** the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo *** analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive *** findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

关键词： adolescents cytokines efficacy Goji berry inflammatory responses interleukin-17A Lycium barbarum polysaccharide randomized controlled study subthreshold depression

The new era of cardiovascular research:revolutionizing cardiovascular research with 3D models in a dish

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Medical Review 2024年第1期4卷 68-85页

作者： Yuan Yang Hao Yang Fedir N.Kiskin Joe Z.Zhang Institute of Neurological and Psychiatric disorders Shenzhen Bay LaboratoryShenzhenGuangdong ProvinceChina Institute of Neurological and Psychiatric disorders Shenzhen Bay LaboratoryShenzhen 518132Guangdong ProvinceChina

Cardiovascular research has heavily relied on studies using patient samples and animal ***,patient studies often miss the data from the crucial early stage of cardiovascular diseases,as obtaining primary tissues at this stage is *** animal models can offer some insights into disease mechanisms,although they usually do not fully recapitulate the phenotype of cardiovascular diseases and their *** recent years,a promising breakthrough has emerged in the form of in vitro three-dimensional(3D)cardiovascular models utilizing human pluripotent stem *** innovative models recreate the intricate 3D structure of the human heart and vessels within a controlled *** advancement is pivotal as it addresses the existing gaps in cardiovascular research,allowing scientists to study different stages of cardiovascular diseases and specific drug responses using human-origin *** this review,we first outline various approaches employed to generate these *** then comprehensively discuss their applications in studying cardiovascular diseases by providing insights into molecular and cellular changes associated with cardiovascular condi***,we highlight the potential of these 3D models serving as a platform for drug testing to assess drug efficacy and *** their immense potential,challenges persist,particularly in maintaining the complex structure of 3D heart and vessel models and ensuring their function is comparable to real ***,overcoming these challenges could revolutionize cardiovascular *** has the potential to offer comprehensive mechanistic insights into human-specific disease processes,ultimately expediting the development of personalized therapies.

关键词： pluripotent stem cells three-dimensional(3D)models cardiac microtissues cardiac organoids vessel organoids organ-on-a-chip