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Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

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Neural Regeneration Research 2024年第12期19卷 2684-2697页

作者： Songqiang Huang Wanting Dong Xiaoqian Lin Jinsong Bian Department of Pharmacology Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Department of Pharmacology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

关键词： antibody biological functions cellular communication electrochemical gradient ion balance ion channels Na^(+)/K^(+)-ATPase neurological diseases neurotransmitter release signal transduction

Evolution of HIV/AIDS Prevention and Control Policies in China:A Grounded Theory Approach

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China CDC weekly 2024年第1期6卷 12-22页

作者： Huang Li Rui Gao Chichen Zhang School of Public Health Southern Medical UniversityGuangzhou CityGuangdong ProvinceChina School of Health Management Southern Medical UniversityGuangzhou CityGuangdong ProvinceChina Key laboratory of Philosophy and Social Sciences of Colleges and Universities in guangdong province for Collaborative Innovation of Health Management Policy and Precision Health Service Southern Medical UniversityGuangzhou CityGuangdong ProvinceChina Graduate School Xi’an Jiaotong-Liverpool UniversitySuzhou CityJiangsu ProvinceChina School of Political Science and Public Administration Soochow UniversitySuzhou CityJiangsu ProvinceChina

Objective:This study aims to provide a theoretical foundation for the development and practical application of human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)prevention and control policy systems in China by scrutinizing,analyzing,and synthesizing the evolution of Chinese policies in this domain.Methods:Utilizing grounded theory,we employed NVivo12 software to perform text content analysis,mining,and coding classification,along with visualization techniques,on policy texts sourced from Chinese government platforms,including the official website of China’s State Council.We considered four analytical dimensions—time,subject,type,and object.Results:The National Health Commission and the State Council emerged as the primary entities engaged in policymaking for HIV/AIDS in China.We identified four distinct stages in the evolution of these policies,culminating in a novel‘sun-shaped’HIV/AIDS prevention and control policy network model with an emphasis on‘knowledge,attitude,and practice’at its nucleus,which aligns with national conditions and societal progress.Furthermore,the focal groups of these policies have been dynamically refined and updated over time.Conclusions:Our findings introduce a‘sunshaped’HIV/AIDS prevention and control policy network model specific to China.We observed a conceptual policy shift towards prioritizing overall human health rather than confining the focus to disease treatment.Additionally,in light of China’s growing elderly population,the imperative to address HIV/AIDS prevention and control among older adults is an issue that warrants increased attention.

关键词： prevention HIV/AIDS policy

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 responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In 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 group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These 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

Relationship among Parkinson’s disease, constipation, microbes, and microbiological therapy

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World Journal of Gastroenterology 2024年第3期30卷 225-237页

作者： Xin-Yang Yuan Yu-Sen Chen Zhou Liu Department of Neurology Affiliated Hospital of Guangdong Medical UniversityZhanjiang 524000Guangdong ProvinceChina Institute of Neurology Guangdong Key Laboratory of Age-Related Cardiac and Cerebral DiseasesZhanjiang 524000Guangdong ProvinceChina

This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson’s disease(PD),a prevalent non-motor symptom contributing significantly to patients’morbidity.A marked alteration in the gut microbiota,predominantly an increase in the abundance of Proteobacteria and Bacteroidetes,is observed in PD-related constipation.Conventional treatments,although safe,have failed to effectively alleviate symptoms,thereby necessitating the development of novel therapeutic strategies.Microbiological interventions such as prebiotics,probiotics,and fecal microbiota transplantation(FMT)hold therapeutic potential.While prebiotics improve bowel movements,probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort.FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD.Despite promising developments,the causal relationship between changes in gut microbiota and PD-related constipation remains elusive,highlighting the need for further research in this expanding field.

关键词： Parkinson disease Constipation Gut microbiota Prebiotics Probiotics Fecal microbiota transplantation

A core scientific problem in the treatment of central nervous system diseases:newborn neurons

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Neural Regeneration Research 2024年第12期19卷 2588-2601页

作者： Peng Hao Zhaoyang Yang Kwok-Fai So Xiaoguang Li Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina guangdong-HongKong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland laboratory(Guangzhou Regenerative Medicine and Health guangdong laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central ne

关键词： bioactive materials brain trauma endogenous neurogenesis hippocampal dentate gyrus neural stem cells neurotrophic factors newborn neurons spinal cord injury stroke subventricular zone

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1361-1373页

作者： Wen-Feng Luo Yu-Ting Jiao Xiao-Ling Lin Ying Zhao Sheng-Bo Wang Jian Shen Jie Deng Yu-Feng Ye Ze-Ping Han Fang-Mei Xie Jin-Hua He Yu Wan Central laboratory of Panyu Central Hospital Guangzhou Panyu Central HospitalGuangzhou 511400Guangdong ProvinceChina South China Normal university-Panyu Central Hospital joint laboratory of Translational Medical Research Guangzhou Panyu Central HospitalGuangzhou 511400Guangdong ProvinceChina Digestive Disease Center Guangzhou Panyu Central HospitalGuangzhou 511400Guangdong ProvinceChina Shunde Vocational and Technical College Foshan 528300Guangdong ProvinceChina Medical Imaging Institute of Panyu Guangzhou Panyu Central HospitalGuangzhou 511400Guangdong ProvinceChina

BACKGROUND Colorectal cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.Syndecan-2 methylation(mSDC2)testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.Cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.AIM To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China.METHODS A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing.Sensitivity and specificity for CRC,advanced adenoma(AA)and advanced colorectal neoplasia(ACN)were determined.High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test.RESULTS A total of 1035 high-risk individuals were included in this study according to established criteria.Among them,16 suffered from CRC(1.55%),65 from AA(6.28%)and 189 from non-AAs(18.26%);150 patients were diagnosed with polyps(14.49%).Diagnoses were established based upon colonoscopic and pathological examinations.Sensitivities of the mSDC2 test for CRC and AA were 87.50%and 40.00%,respectively;specificities were 95.61%for other groups.Positive predictive values of the mSDC2 test for CRC,AA and ACN were 16.09%,29.89%and 45.98%,respectively;the negative predictive value for CRC was 99.79%.After adjusting for other high-risk covariates,mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN(P<0.001).CONCLUSION Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

关键词： Colorectal cancer Syndecan-2 DNA methylation Chinese population

Lycium barbarum glycopeptide(wolfberry extract)slows N-methyl-N-nitrosourea-induced degradation of photoreceptors

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Neural Regeneration Research 2024年第10期19卷 2290-2298页

作者： Qihang Kong Xiu Han Haiyang Cheng Jiayu Liu Huijun Zhang Tangrong Dong Jiansu Chen Kwok-Fai So Xuesong Mi Ying Xu Shibo Tang Department of Ophthalmology Aier Eye HospitalJinan UniversityGuangzhouGuangdong ProvinceChina Department of Ophthalmology The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina guangdong-Hong Kong-Macao Institute of CNS Regeneration Key Laboratory of CNS Regeneration(Ministry of Education)Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Ophthalmology Guangzhou Panyu Central HospitalGuangzhouGuangdong ProvinceChina School of Stomatology Jinan UniversityGuangzhouGuangdong ProvinceChina Aier Academician Station ChangshaHunan ProvinceChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina State Key laboratory of Brain and Cognitive Sciences Hong Kong Special Administrative RegionChina

Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum(L. barbarum) polysaccharide(LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide(Lb GP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of Lb GP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of Lb GP as a protective pre-treatment on days 1–7;intraperitoneal administration of 40 mg/kg N-methylN-nitrosourea to induce photoreceptor injury on day 7;and continuation of orally administered Lb GP on days 8–14. Treatment with Lb GP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. Lb GP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, Lb GP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration.

关键词： anti-inflammation inherited retinal diseases Lycium barbarum glycopeptide N-methyl-N-nitrosourea opsin photoreceptor reactive gliosis retinal degeneration retinitis pigmentosa rhodopsin

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

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Neural Regeneration Research 2024年第3期19卷 650-656页

作者： Jie Li Wen Jiang Yuefang Cai Zhenqiu Ning Yingying Zhou Chengyi Wang Sookja Ki Chung Yan Huang Jingbo Sun Minzhen Deng Lihua Zhou Xiao Cheng Guangzhou university of Traditional Chinese Medicine GuangzhouGuangdong ProvinceChina State Key laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina guangdong Provincial Key laboratory of Research on Emergency in TCM GuangzhouGuangdong ProvinceChina Department of Anesthesiology West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Anatomy Sun Yat-Sen School of MedicineSun Yat-Sen UniversityShenzhenGuangdong ProvinceChina Faculty of Medicine Macao University of Science and TechnologyMacao Special Administration RegionChina

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

关键词： astrocytic endothelin-1 dentate gyrus differentially expressed proteins hippocampus ischemic stroke learning and memory deficits lipid metabolism neural stem cells neurogenesis proliferation

Targeting tau in Alzheimer's disease:from mechanisms to clinical therapy

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Neural Regeneration Research 2024年第7期19卷 1489-1498页

作者： Jinwang Ye Huali Wan Sihua Chen Gong-Ping Liu Shenzhen Key laboratory of Marine Biotechnology and Ecology College of Life Sciences and OceanographyShenzhen UniversityShenzhenGuangdong ProvinceChina Department of laboratory Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Co-innovation Center of Neurodegeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Pathophysiology School of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.

关键词： acetylation Alzheimer’s disease cognitive deficits gliosis mitochondria damage neuroinflammation phosphorylation synaptic impairments tau tau immunotherapy