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New glucocerebrosidase antibodies can advance research in the field of neurodegenerative disorders

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Neural Regeneration Research 2025年第4期20卷 1085-1086页

作者： Charis Ma Krystyna Rytel Yu Chen Ellen Sidransky medical genetics Branch National Human Genome Research InstituteNational Institutes of HealthBethesdaMDUSA

In medical research,there are times when the introduction of a new tool can launch scientific discovery in new *** antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)research,the dearth of validated antibodies for different applications has impeded progress in studies of disease pathogenesis and therapeutic *** recent introduction of new,rigorously evaluated antibodies can now propel research into the link between glucocerebrosidase and Parkinson’s disease(PD)as well as aspects of the pathobiology of Gaucher disease(Jong et al.,2024).

关键词： antibodies cerebro

Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou Michael G.Fehlings Division of genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of medical Science University of TorontoTorontoONCanada Division of Neurosurgery and Spine program Department of SurgeryUniversity of TorontoTorontoONCanada

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

Extracellular vesicles as tools and targets in therapy for diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 872-912页

作者： Mudasir A.Kumar Sadaf K.Baba Hana Q.Sadida Sara Al.Marzooqi Jayakumar Jerobin Faisal H.Altemani Naseh Algehainy Mohammad A.Alanazi Abdul-Badi Abou-Samra Rakesh Kumar Ammira S.Al-Shabeeb Akil Muzafar A.Macha Rashid Mir Ajaz A.Bhat Watson-Crick Centre for Molecular Medicine Islamic University of Science and TechnologyAwantiporaKashmir 192122India Department of human genetics-Precision Medicine in Diabetes Obesity and Cancer ProgramSidra MedicineDohaQatar Qatar Metabolic Institute Academic Health SystemHamad Medical CorporationDohaQatar Department of medical Laboratory Technology Prince Fahad Bin Sultan Chair for Biomedical ResearchFaculty of Applied Medical SciencesUniversity of TabukTabukSaudi Arabia School of Biotechnology Shri Mata Vaishno Devi UniversityKatraIndia

Extracellular vesicles(EVs)are nano-sized,membranous structures secreted into the extracellular *** exhibit diverse sizes,contents,and surface markers and are ubiquitously released from cells under normal and pathological *** serum is a rich source of these EVs,though their isolation from serum proteins and non-EV lipid particles poses *** vesicles transport various cellular components such as proteins,mRNAs,miRNAs,DNA,and lipids across distances,influencing numerous physiological and pathological events,including those within the tumor microenvironment(TME).Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents,drug delivery systems,and disease *** in cancer diagnostics,EV detection can pave the way for early identification and offers potential as diagnostic ***,various EV subtypes are emerging as targeted drug delivery tools,highlighting their potential clinical *** need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains *** into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the *** this review,we discuss in detail the roles of EVs across various conditions,including cancers(encompassing head and neck,lung,gastric,breast,and hepatocellular carcinoma),neurodegenerative disorders,diabetes,viral infections,autoimmune and renal diseases,emphasizing the potential advancements in molecular diagnostics and drug delivery.

关键词： diseases sized sizes

Cell-type resolved transcriptomic approaches for dissecting selective vulnerability in neurodgeneration

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Neural Regeneration Research 2024年第7期19卷 1411-1413页

作者： Caleb A.Wood Nicholas M.Tran Department of Neuroscience Baylor College of MedicineHoustonTXUSA Department of Molecular and human genetics Baylor College of MedicineHoustonTXUSA

A common feature among neurodegenerative conditions is that ce rtain neuronal populations are selectively vulnerable to loss(Fu et al.,2018).By corollary,other neurons are selectively resilient,suggesting they may possess unique features that support their survival.U nderstanding the basis of neuronal resilience or vulnerability would provide a logical strategy to identify factors that could be targeted therapeutically.

关键词： selective targeted

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

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World Journal of Diabetes 2024年第4期15卷 606-622页

作者： Ashwin Kumar Shukla Komal Awasthi Kauser Usman Monisha Banerjee Molecular and human genetics Laboratory Department of ZoologyUniversity of LucknowLucknow 226007Uttar PradeshIndia Department of Medicine King Georges’Medical UniversityLucknow 226003Uttar PradeshIndia Institute of Advanced Molecular genetics and Infectious Diseases(IAMGID)University of LucknowLucknow 226007Uttar PradeshIndia

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 *** has affected over 768 million people worldwide,resulting in approx-imately 6900000 ***-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney *** indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic *** the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 *** converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a *** ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and *** ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 *** review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in *** treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

关键词： Angiotensin-converting enzyme 2 Angiotensin-converting enzyme inhibitors Angiotensin-II receptor blockers Complex diseases COVID-19 Type 2 diabetes

Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 241-254页

作者： Chenjun Hu Yiqun Yan Yanhong Jin Jun Yang Yongmei Xi Zhen Zhong Department of Neurology of the Second Afliated Hospital and Department of human Anatomy Histology and EmbryologyZhejiang University School of MedicineHangzhou 310058China Department of Physiology and Department of Cardiology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Division of human Reproduction and Developmental genetics Women’s Hospital and Institute of GeneticsZhejiang University School of MedicineHangzhou 310006China

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral *** a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into *** and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent *** review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and *** on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also *** lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关键词： Neurodegenerative diseases Prion-like propagation Seeding Endocytosis Endolyosomal leaking Degradation

High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of genetics and Medicine TIGEMPozzuoliNaples 80131Italy medical genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and human genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 307-323页

作者： Xufeng FU Hang HAN Hong YANG Bo XU Wenjie DAI Ling LIU Tiantian HE Xing DU Xiuying PEI Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China Key Laboratory of Reproduction and genetics in Ningxia Ningxia Medical UniversityYinchuan 750004China

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain *** this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in ***,whole-body imaging found that PS-NPs accumulated in the testes of ***,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were *** oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were *** spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP *** phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by ***,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive *** study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

关键词： Polvstyrene nanoplastics(PS-NPs) Reproductive toxicity Ferroptosis Nuclear factor ervthroid 2-related factor 2(Nrf2)

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