检索结果-南通市图书馆

Roles of neuronal lysosomes in the etiology of Parkinson’s disease

Neural Regeneration Research 2024年第9期19卷 1981-1983页

作者： Mattia Volta institute for biomedicine Eurac ResearchBolzanoItaly

Therapeutic progress in neurodegenerative conditions such as Parkinson’s disease has been hampered by a lack of detailed knowledge of its molecular etiology.The advancements in genetics and genomics have provided fundamental insights into specific protein players and the cellular processes involved in the onset of disease.In this respect,the autophagy-lysosome system has emerged in recent years as a strong point of convergence for genetics,genomics,and pathologic indications,spanning both familial and idiopathic Parkinson’s disease.Most,if not all,genes linked to familial disease are involved,in a regulatory capacity,in lysosome function(e.g.,LRRK2,alpha-synuclein,VPS35,Parkin,and PINK1).Moreover,the majority of genomic loci associated with increased risk of idiopathic Parkinson’s cluster in lysosome biology and regulation(GBA as the prime example).Lastly,neuropathologic evidence showed alterations in lysosome markers in autoptic material that,coupled to the alpha-synuclein proteinopathy that defines the disease,strongly indicate an alteration in functionality.In this Brief Review article,I present a personal perspective on the molecular and cellular involvement of lysosome biology in Parkinson’s pathogenesis,aiming at a larger vision on the events underlying the onset of the disease.The attempts at targeting autophagy for therapeutic purposes in Parkinson’s have been mostly aimed at“indiscriminately”enhancing its activity to promote the degradation and elimination of aggregate protein accumulations,such as alpha-synuclein Lewy bodies.However,this approach is based on the assumption that protein pathology is the root cause of disease,while pre-pathology and pre-degeneration dysfunctions have been largely observed in clinical and pre-clinical settings.In addition,it has been reported that unspecific boosting of autophagy can be detrimental.Thus,it is important to understand the mechanisms of specific autophagy forms and,even more,the adjustment of specific lysosome functionalities.Indeed,lysosomes exert fine signa

关键词： alpha-synuclein autophagy LRRK2 lysosome neuroprotection neurotransmission Parkinson’s disease Rit2 synapse

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

A sphingolipid message promotes neuronal health across generations

引用

Neural Regeneration Research 2024年第11期19卷 2325-2326页

作者： Wenyue Wang Roger Pocock Development and Stem Cells Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVICAustralia

Maternal nutrition can affect brain function of offspring in later life(Fitzgerald et al.,2020).Emerging studies have also shown that the maternal environment can modify susceptibility to neurodegenerative disease(Boots et al.,2023).Transmission of environmental information from mother to offspring depends on maternal nutrient provisioning.In the nematode Caenorhabditis elegans,maternal yolk,which is synthesized in the intestine and transferred to nourish oocytes and early embryos,can provide extranuclear inheritance factors to mediate phenotypic plasticity across generations.However,the molecular mechanisms of regulating such intergenerational effects remain largely unknown.

关键词： mother intestine transferred

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Hypoxia-inducible factor-1αin myocardial infarction

引用

World Journal of Cardiology 2024年第4期16卷 181-185页

作者： IvanaŠkrlec Sergey N Kolomeichuk Faculty of Dental Medicine and Health Josip Juraj Strossmayer University of OsijekOsijek 31000Croatia institute of biology Karelia Research Center of Russian Academy of SciencesPetrozavodsk 185910Russia Laboratory for Genomics Proteomicsand MetabolomicsResearch Institute of Biomedicine and Biomedical TechnologiesTyumen State Medical UniversityTyumen 625023Russia

Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischemia,is because of its ability to alleviate cardiac dysfunction.The oxygen-responsive subunit,HIF1α,plays a crucial role in this process,as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival,angiogenesis,and metabolism.Furthermore,HIF1αexpression induced reperfusion in the ischemic skeletal muscle,and hypoxic skin wounds in diabetic animal models showed reduced HIF1αexpression.Increased expression of HIF1αhas been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial infarction.Genetic variations in HIF1αhave also been found to correlate with altered responses to ischemic cardiovascular disease.In addition,a link has been established between the circadian rhythm and hypoxic molecular signaling pathways,with HIF1αfunctioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in light.This editorial analyzes the relationship between HIF1αand the circadian rhythm and highlights its significance in myocardial adaptation to hypoxia.Understanding the changes in molecular signaling pathways associated with diseases,specifically cardiovascular diseases,provides the opportunity for innovative therapeutic interventions,especially in low-oxygen environments such as myocardial infarction.

关键词： Cardiovascular pathologies Circadian genes Hypoxia-inducible factor 1 Hypoxia Gene-gene interaction

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

引用

Zoological Research 2024年第2期45卷 253-262页

作者： Yang Han Jiale Zhou Renquan Zhang Yuru Liang Liangxue Lai Zhanjun Li Key Laboratory of Zoonosis Research Ministry of EducationCollege of Animal ScienceJilin UniversityChangchunJilin 130062China CAS Key Laboratory of Regenerative biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Guangzhou Regenerative Medicine and Health Guang Dong Laboratory(GRMH-GDL) GuangzhouGuangdong 510005China institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

关键词： Genome editing Animal model Rabbit CRISPR/Cas9 Genetic diseases

来源：

维普期刊数据库

同方期刊数据库博看期刊评论

在线全文

学校读者我要写书评

暂无评论

Physical exercise and traumatic brain injury: is it question of time?

引用

Neural Regeneration Research 2024年第3期19卷 475-476页

作者： Valentina Mastrorilli Stefano Farioli Vecchioli institute of Biochemistry and Cell biology Institute of Biochemistry and Cell BiologyNational Research Council(IBBC/CNR)MonterotondoRomeItaly Plaisant S.R.L. RomeItaly

Is it better to be safe than sorry?This Hamletic dilemma has always stimulated medical-scientific debates in numerous fields of biomedicine.And among these,the preventive-therapeutic approach to the treatment of brain trauma is one of the most striking examples.Traumatic brain injury(TBI)is a leading cause of brain damage among young and elderly populations with a very high hospitalization and death rate.TBI is characterized by two pathologically distinct but strictly consequential phases:a first characterized by an immediate and highly variable mechanical dysfunction of the brain tissue,which involves widespread cell death and tissue degeneration,followed by a second phase which can last from days to even years depending on the severity of the TBI and the patient’s pre-existing health status.Secondary processes,including inflammatory phenomena,oxidative stress associated with metabolic,vascular,and neuro-modulatory deficits,are very often responsible for neuro-motor and psychological deficits leading to long-term disabilities(Kaur and Sharma,2018).

关键词： injury striking modulator

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

引用

Neural Regeneration Research 2025年第5期20卷 1411-1413页

作者： Marcos J.Arauzo-Bravo Daniela Gerovska Matthias Schwab Alexandra Kretz Computational biology and Systems biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany Department of Cell biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain Department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic al. sclerosis

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Inbreeding and genetic load in a pair of sibling grouse species:Tetrastes sewersowi and T.bonasia

引用

Avian Research 2024年第2期15卷 265-270页

作者： Kai Song Tom van der Valk Bin Gao Peter Halvarsson Yun Fang Wendong Xie Siegfried Klaus Zhiming Han Yue-Hua Sun Jacob Hoglund Key Laboratory of Animal Ecology and Conservation biology Institute of ZoologyChinese Academy of SciencesBeijing100101China Animal Ecology Department of Ecology and GeneticsUppsala UniversityNorbyvagen 18DUppsala75236Sweden Department of Cell and Molecular biology Uppsala75273Sweden Unit of Parasitology Department of Biomedicine and Veterinary Public HealthSwedish University of Agricultural SciencesPO Box 7036Uppsala75007Sweden Lindenhohe 5 JenaD-07749Germany The State Key Laboratory of Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijing100101China

Genetic load and inbreeding are recognized as important factors to be considered in conservation programs.Elevated levels of both can increase the risk of population extinction by negatively impacting fitness-related characters in many species of plants and animals,including humans(inbreeding depression).Genomic tech-niques are increasingly used in measuring and understanding genetic load and inbreeding and their importance in evolution and conservation.We used whole genome resequencing data from two sibling grouse species in subarctic Eurasia to quantify both.We found a large range of inbreeding measured as FROH(fraction of runs of homozygosity)in individuals from different populations of Chinese Grouse(Tetrastes sewerzowi)and Hazel Grouse(T.bonasia).FROH estimated from genome-wide runs of homozygosity(ROH)ranged from 0.02 to 0.24 among Chinese Grouse populations and from 0.01 to 0.44 in Hazel Grouse.Individuals from a population of Chinese Grouse residing in the Qilian mountains and from the European populations of Hazel Grouse(including samples from Sweden,Germany and Northeast Poland)were the most inbred(FROH ranged from 0.10 to 0.23 and 0.11 to 0.44,respectively).These levels are comparable to other highly inbred populations of birds.Hazel Grouse from northern China and Chinese Grouse residing in the Qinghai-Tibetan Plateau showed relatively lower inbreeding levels.Comparisons of the ratio between deleterious missense mutations and synonymous mutations revealed higher levels in Chinese Grouse as compared to Hazel Grouse.These results are possibly explained by higher fixation rates,mutational melt down,in the range-restricted Chinese Grouse compared to the wide-ranging Hazel Grouse.However,when we compared the relatively more severe class of loss-of-function muta-tions,Hazel Grouse had slightly higher levels than Chinese Grouse,a result which may indicate that purifying selection(purging)has been more efficient in Chinese Grouse on this class of mutations.

关键词： Genetic load Inbreeding Purifying selection Qinghai-Tibetan Plateau ROH Tetrastes

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies

引用

Cancer biology & Medicine 2024年第4期21卷 331-346页

作者： Shuangcheng Li Tianci Wang Xinghui Xiao Xiaodong Zheng Haoyu Sun Rui Sun Hongdi Ma Zhigang Tian Xiaohu Zheng Hefei National Research Center for Physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China institute of Immunology University of Science and Technology of ChinaHefei 230027China Hefei TG ImmunoPharma Corporation Limited Hefei 230601China Research Unit of NK Cell Study Chinese Academy of Medical SciencesBeijing 100864China Key Laboratory of Quantitative Synthetic biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

关键词： NK cell CD300A phosphatidylserine immune checkpoint hematologic malignancy

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Remaking a connection:molecular players involved in post-injury synapse formation

引用

Neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： Diogo Tomé Ramiro D.Almeida iBiMED-institute of biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CNC-Center for Neuroscience and Cell biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate targets.Although several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after injury.Herein,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

关键词： viable injury instru

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancer

引用

National Science Review 2024年第1期11卷 107-119页

作者： Shuren Zhang Dongfan Song Wenhao Yu Ji Li Xiaoyu Wang Yachao Li Zihan Zhao Qi Xue Jing Zhao Jie P.Li Zijian Guo State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center (ChemBIC) Nanjing University Department of Urology Afflliated Drum Tower HospitalMedical SchoolNanjing University Nanchuang (Jiangsu)institute of Chemistry and Health

Mounting evidence suggests that strategies combining DNA-damaging agents and stimulator of interferon genes(STING) agonists are promising cancer therapeutic regimens because they can amplify STING activation and remodel the immunosuppressive tumor microenvironment. However, a single molecular entity comprising both agents has not yet been developed. Herein, we designed two PtIV-MSA-2 conjugates(Ⅰand Ⅱ) containing the DNA-damaging chemotherapeutic drug cisplatin and the innate immuneactivating STING agonist MSA-2; these conjugates showed great potential as multispecific small-molecule drugs against pancreatic cancer. Mechanistic studies revealed that conjugate Ⅰ upregulated the expression of transcripts associated with innate immunity and metabolism in cancer cells, significantly differing from cisplatin and MSA-2. An analysis of the tumor microenvironment demonstrated that conjugate I could enhance the infiltration of natural killer(NK) cells into tumors and promote the activation of T cells, NK cells and dendritic cells in tumor tissues. These findings indicated that conjugate I, which was created by incorporating a Pt chemotherapeutic drug and STING agonist into one molecule, is a promising and potent anticancer drug candidate, opening new avenues for small-molecule-based cancer metalloimmunotherapy.

关键词： platinum drug STING agonist single-molecule multitarget metalloimmunology

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：