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Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International human Phenome Institutes(Shanghai) ShanghaiChina human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of genetics and Genomics 2024年第2期51卷 133-143页

作者： Yi Zhang Zhi-Ying Wu department of Medical genetics and Center for Rare Diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Medical Neurobiology of Zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

Clathrin light chains negatively regulate plant immunity by hijacking the autophagy pathway

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Plant Communications 2024年第8期5卷 172-188页

作者： Hu-Jiao Lan Jie Ran Wen-Xu Wang Lei Zhang Ni-Ni Wu Ya-Ting Zhao Min-Jun Huang Min Ni Fen Liu Ninghui Cheng Paul A.Nakata Jianwei Pan Steven A.Whitham Barbara J.Baker Jian-Zhong Liu Zhejiang Provincial Key Laboratory of Biotechnology on Specialty Economic Plants Zhejiang Normal UniversityJinhua 321004China Institute of Plant genetics and Developmental Biology College of Chemistry and Life SciencesZhejiang Normal UniversityJinhua 321004China College of Life Sciences Lanzhou UniversityLanzhou 730000China department of Plant Pathology and Microbiology Iowa State UniversityAmesIA 50011USA department of Plant and Microbial Biology University of CaliforniaBerkeleyBerkeleyCA 94720USA Plant Gene Expression Center U.S.Department of Agriculture-Agricultural Research ServiceAlbanyCA 94706USA Lushan Botanical Garden Chinese Academy of SciencesJiujiang 332000China U.S.department of Agriculture-Agricultural Research Service Children’s Nutrition Research CenterDepartment of PediatricsBaylor College of MedicineHoustonTX 77030USA

The crosstalk between clathrin-mediated endocytosis(CME)and the autophagy pathway has been reported in mammals;however,the interconnection of CME with autophagy has not been established in ***,we report that the Arabidopsis CLATHRIN LIGHT CHAIN(CLC)subunit 2 and 3 double mutant,clc2-1 clc3-1,phenocopies Arabidopsis AUTOPHAGY-RELATED GENE(ATG)mutants in both autoimmunity and nutrient ***,the autophagy pathway is significantly compromised in the clc2-1 clc3-1 ***,multiple assays demonstrate that CLC2 directly interacts with ATG8h/ATG8i in a domain-specific *** expected,both GFP-ATG8h/GFP-ATG8i and CLC2-GFP are subjected to autophagic degradation,and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 ***,simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum,supporting the functional relevance of the CLC2-ATG8h/8i *** conclusion,our results reveal a link between the function of CLCs and the autophagy pathway in Arabidopsis.

关键词： autophagy clathrin light chain immunity clathrin-mediated endocytosis senescence cell death

Hexafluoropropylene oxide trimer acid,a perfluorooctanoic acid alternative,induces cardiovascular toxicity in zebrafish embryos

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Journal of Environmental Sciences 2024年第5期139卷 460-472页

作者： Sujie Sun Li Zhang Xue Li Lu Zang Ling Huang Junquan Zeng Zigang Cao Xinjun Liao Zilin Zhong Huiqiang Lu Jianjun Chen Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for human Diseases Jiangxi Key Laboratory of Developmental Biology of OrgansCenter for Clinical Research Center of the Affiliated Hospital of Jinggangshan UniversityJi’an 343009China Translational Research Institute of Brain and Brain-like Intelligence Shanghai Key Laboratory of Anesthesiology and Brain Functional ModulationDepartment of PediatricsShanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200434China State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants School of Environmental Sciences and EngineeringShanghai Jiao Tong UniversityShanghai 200240China department of Interventional and Vascular Surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343009China department of Internal Medicine and Hematology Affiliated Hospital of Jinggangshan UniversityJi’an 343009China

As an increasingly used alternative to perfluorooctanoic acid(PFOA),hexafluoropropylene oxide trimer acid(HFPO-TA)has been widely detected in global water ***,little is known regarding its toxic effects on cardiovascular ***,zebrafish embryos were treated with egg water containing 0,60,120,or 240 mg/L *** showed that HFPO-TA treatment led to a significant reduction in both larval survival percentage and heart ***,HFPO-TA exposure caused severe pericardial edema and elongation of the sinus venous to bulbus arteriosus distance(SV-BA)in Tg(myl7:GFP)transgenic larvae,disrupting the expression of genes involved in heart development and thus causing abnormal heart *** sprouting angiogenesis was observed in the 120 and 240 mg/L exposed Tg(fli:GFP)transgenic ***-TA treatment also impacted the mRNA levels of genes involved in the vascular endothelial growth factor(VEGF)pathway and embryonic vascular ***-TA exposure significantly decreased erythrocyte number in Tg(gata1:DsRed)transgenic embryos and influenced gene expression associated with the heme metabolism ***-TA also induced oxidative stress and altered the transcriptional levels of genes related to cell cycle and apoptosis,inhibiting cell proliferation while promoting ***,HFPO-TA exposure may induce abnormal development of the cardiovascular and hematopoietic systems in zebrafish embryos,suggesting it may not be a suitable or safe alternative for PFOA.

关键词： Hexafluoropropylene oxide trimer acid Heart development Vascular development Hemopoiesis Zebrafish embryos

Identification of novel biomarkers for varicocele using iTRAQ LC-MS/MS technology

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Chinese Medical Journal 2024年第3期137卷 371-372页

作者： Xianfeng Lu Na Li Lufang Li Yongai Wu Xuefeng Lyu Yingli Cao Jianrong Liu Qin Qin department of pediatrics Shanxi Provincial People’s HospitalTaiyuanShanxi 030012China department of Reproductive genetics Heping Hospital Affiliated to Changzhi Medical CollegeChangzhiShanxi 046099China department of Biochemistry Basic Medicine CollegeShanxi Medical UniversityTaiyuanShanxi 030607China Reproductive Medical department Shanxi Provincial People’s HospitalTaiyuanShanxi 030012China

To the Editor:Varicocele(VC)is a vascular disease and considered as the main cause of male infertility.^([1])The incidence of VC in the common male population was 4.4–22.6%,of which the incidence of primary infertility was 35–40%,while the incidence of secondary infertility was as high as 80%.^([2])The exact pathophysiological mechanism of male infertility caused by VC and regulative molecules are still *** and definite molecular markers of VC disease are helpful for early prevention and timely *** study aimed to screen candidate regulative molecules playing a role in male infertility caused by VC.

关键词： prevention incidence exact

RNF187 governs the maintenance of mouse GC-2 cell development by facilitating histone H3 ubiquitination at K57/80

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Asian Journal of Andrology 2024年第3期26卷 272-281页

作者： Bing-Ya Xu Xiang-Ling Yu Wen-Xin Gao Ting-Ting Gao Hao-Yue Hu Tian-Tian Wu Cong Shen Xiao-Yan Huang Bo Zheng Yi-Bo Wu human Reproductive and Genetic Center Affiliated Hospital of Jiangnan UniversityWuxi 214122China State Key Laboratory of Reproductive Medicine Department of Histology and EmbryologySchool of Basic Medical SciencesNanjing Medical UniversityNanjing 211166China Changzhou Maternal and Child Health Care Hospital Changzhou Medical CenterNanjing Medical UniversityChangzhou 213000China State Key Laboratory of Reproductive Medicine Center for Reproduction and GeneticsSuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversitySuzhou 215002China

RING finger 187(RNF187),a ubiquitin-ligating(E3)enzyme,plays a crucial role in the proliferation of cancer ***,it remains unclear whether RNF187 exhibits comparable functionality in the development of germline *** investigate thepotential involvement of RNF187 in germ cell development,we conducted interference and overexpression assays using GC-2 cells,a mouse spermatocyte-derived cell *** findings reveal that the interaction between RNF187 and histone H3 increases theviability,proliferation,and migratory capacity of GC-2 ***,we provide evidence demonstrating that RNF187 interactswith H3 and mediates the ubiquitination of H3 at lysine 57(K57)or lysine 80(K80),directly or indirectly resulting in increasedcellular *** is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediatinghistone H3 ubiquitination,thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of *** discoveries provide a new theoretical foundation for further comprehensive investigations into the functionof RNF187 in the reproductive system.

关键词： GC-2 cell histone H3 RNF187 ubiquitination

Impact of umbelliprenin-containing niosome nanoparticles on VEGF-A and CTGF genes expression in retinal pigment epithelium cells

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 7-15页

作者： Farzad Dastaviz Akram Vahidi Teymoor Khosravi Ayyoob Khosravi Mehdi Sheikh Arabi Abouzar Bagheri Mohsen Rashidi Morteza Oladnabi Stem Cell Research Center Golestan University of Medical SciencesGorgan ***Iran department of Medical genetics School of Advanced Technologies in MedicineGolestan University of Medical SciencesGorgan ***Iran Student Research Committee Golestan University of Medical SciencesGorgan ***Iran department of Molecular Medicine Faculty of Advanced Medical TechnologiesGolestan University of Medical SciencesGorgan ***Iran department of Medical Nanotechnology Faculty of Advanced Medical TechnologiesGolestan University of Medical SciencesGorgan ***Iran department of Clinical Biochemistry and genetics Faculty of MedicineMazandaran University of Medical SciencesSari ***Iran department Pharmacology Faculty of MedicineMazandaran University of Medical SciencesSari ***Iran Gorgan Congenital Malformations Research Center Golestan University of Medical SciencesGorgan ***Iran

AIM:To investigate the impact of niosome nanoparticles carrying umbelliprenin(UMB),an anti-angiogenic and anti-inflammatory plant compound,on the expression of vascular endothelial growth factor(VEGF-A)and connective tissue growth factor(CTGF)genes in a human retinal pigment epithelium(RPE)-like retina-derived cell ***:UMB-containing niosomes were created,optimized,and ***-like cells were treated with free UMB and UMB-containing *** IC_(50)values of the treatments were determined using an MTT *** expression of VEGF-A and CTGF was evaluated using real-time polymerase chain reaction after RNA extraction and cDNA ***’characteristics,including drug entrapment efficiency,size,dispersion index,and zeta potential were *** UMB had an IC_(50)of 96.2μg/mL,while UMB-containing niosomes had an IC_(50)of 25μg/***:Treatment with UMB-containing niosomes and free UMB resulted in a significant reduction in VEGF-A expression compared to control cells(P=0.001).Additionally,UMB-containing niosomes demonstrated a significant reduction in CTGF expression compared to control cells(P=0.05).However,there was no significant reduction in the expression of both genes in cells treated with free ***:Both free UMB and niosome-encapsulated UMB inhibits VEGF-A and CTGF genes ***,the latter demonstrates significantly greater efficacy,potentially due to the lower UMB dosage and gradual *** findings have implications for anti-angiogenesis therapeutic approaches targeting age-related macular degeneration.

关键词： umbelliprenin niosome age-related macular degeneration vascular endothelial growth factor-A connective tissue growth factor

TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma *** Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was *** Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-*** addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

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Zoological Research 2024年第3期45卷 535-550页

作者： Laidong Yu Fangfang Zeng Mengshu Fan Kexuan Zhang Jingjing Duan Yalu Tan Panlin Liao Jin Wen Chenyu Wang Meilin Wang Jialong Yuan Xinxin Pang Yan Huang Yangzhou Zhang Jia-Da Li Zhuohua Zhang Zhonghua Hu Hunan Key Laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China Center for Medical genetics and Hunan Key Laboratory of Medical genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Provincial Clinical Research Center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Key Laboratory of Animal Models for human Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China MOE Key Lab of Rare Pediatric Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China department of Neurosciences University of South China Medical SchoolHengyangHunan 421001China

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain *** abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric *** 17(PCDH17)is associated with major mood disorders,including bipolar disorder and ***,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain *** this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory *** overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in ***,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)***,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine ***,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

关键词： Synapse development Dendritic spine Mood disorder Actin cytoskeleton Animal behavior