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Photo-activated microtubule targeting drugs: Advancing therapies for colorectal cancer

World Journal of Gastroenterology 2024年第26期30卷 3257-3260页

作者： Naresh Singh Samantha Sharma department of medical and Molecular {2. Indiana University School of MedicineIndianapolisIN 46202United States

Over the years immunotherapy has demonstrably improved the field of cancer ***,achieving long-term survival for colorectal cancer(CRC)patients remains a significant unmet *** immunotherapies incor-porating targeted drugs like MEK or multi-kinase inhibitors have offered some palliative ***,substantial gaps remain in the current therapeutic armamentarium for *** recent years,there has been a surge of interest in exploring novel treatment strategies,including the application of light-activated drugs in conjunction with optical *** approach holds promise for achie-ving localized and targeted delivery of cytotoxic agents,such as microtubule-targeting drugs,directly to cancerous cells within the colon.

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Apoer2.Lrp8:the undercover cop of synaptic homeostasis

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Neural Regeneration Research 2024年第12期19卷 2563-2564页

作者： Gordon C.Werthmann Joachim Herz department of Molecular genetics and Center for Translational Neurodegeneration Research University of Texas Southwestern Medical Center at DallasDallasTXUSA department of Neuroscience department of Neurology University of Texas Southwestern medical Center at Dallas DallasTXUSA

Apolipoprotein E receptor 2.ApoER2.is a receptor for the protein ApoE,the most common genetic risk factor for late-onset Alzheimer's disease(AD).It is also a key modulator of syna ptic homeostasis,in part through its effect on the expression of neuronal genes including those implicated in AD and other neuropsychiatric *** this perspective,we highlight several genes affected by ApoER2.and its alternatively spliced forms and how aberrant expression can be rescued by the reintroduction of the ApoER2.intracellular domain in the mouse hippocampus.

关键词： homeostasis ApoE Alzheimer

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The next decade of SET:from an oncoprotein to beyond

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Journal of Molecular Cell Biology 2024年第1期16卷 1-14页

作者： Han Yao Meng Zhang Donglai Wang State Key Laboratory of Common Mechanism Research for Major Diseases&department of medical {2. Institute of Basic Medical Sciences&School of Basic MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

This year marks the fourth decade of research into the protein SET,which was discovered in *** was initially identified as an oncoprotein but later shown to be a multifaceted protein involved in regulating numerous biological processes under both physiological and pathophysiological *** dysfunction is closely associated with diseases,such as cancer and Alzheimer's *** the increasing understanding of how SET works and how it is regulated in cells,targeting aberrant SET has emerged as a potential strategy for disease *** this review,we present a comprehensive overview of the advancements in SET studies,encompassing its biological functions,regulatory networks,clinical implications,and pharmacological ***,we provide insights into the future prospects of SET research,with a particular emphasis on its promising potential in the realm of immune modulation.

关键词： SET biological process regulatory mechanism disease therapy

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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,2. 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

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Mitochondrial DNA methylation and mitochondria-related epigenetics in neurodegeneration

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Neural Regeneration Research 2024年第2期19卷 405-406页

作者： Fabio Coppedè department of Translational Research and of New Surgical and medical Technologies Laboratory of Medical GeneticsUniversity of PisaPisaItaly、Interdepartmental Research Center of Biology and Pathology of AgingUniversity of PisaPisaItaly

Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy *** are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.

关键词： impaired neurodegeneration oxidative

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Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

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Neural Regeneration Research 2024年第7期19卷 1602-1607页

作者： Mingri Zhao Xun Chen Jiangfeng Liu Yanjin Feng Chen Wang Ting Xu Wanxi Liu Xionghao Liu Mujun Liu Deren Hou department of Neurology The Third Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Center for medical genetics&Hunan Key Laboratory of medical genetics School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina department of Cell Biology School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s ***1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor *** better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 *** found that Sorl1-knocko ut mice displayed deficits in learning and ***,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout *** vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were *** expression of synaptic proteins,including Drebrin and NR2.,was significantly reduced,and also their ***,by knocking out the Sorl1 gene in N2. cells,we found that expression of the N-methyl-D-aspartate receptor,NR2.,and cyclic adenosine monophosphate-response element binding protein was also *** findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2./cyclic adenosine monophosphate-response element binding protein signaling axis.

关键词： brain-derived neurotrophic factor late-onset Alzheimer’s disease N-methyl-D-aspartate receptor sortilin-related receptor 1 synapse

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Promising dawn in tumor microenvironment therapy:engineering oral bacteria

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International Journal of Oral Science 2024年第2期16卷 208-224页

作者： Zifei Wang Wansu Sun Ruixue Hua Yuanyin Wang Yang Li Hengguo Zhang Key Laboratory of Oral Diseases Research of Anhui Province College&Hospital of StomatologyAnhui Medical UniversityHefeiChina department of Stomatology The First Affiliated Hospital of Anhui Medical UniversityHefeiChina department of genetics School of Life ScienceAnhui Medical UniversityHefeiChina

Despite decades of research,cancer continues to be a major global health *** human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via ***,the role of oral microbes in the development and progression of cancer has received increasing *** the same time,bioengineering technology and nanotechnology is growing rapidly,in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of *** engineered bacteria were transformed to achieve directed genetic reprogramming,selective functional reorganization and precise *** contrast to endotoxins produced by typical genetically modified bacteria,oral flora exhibits favorable biosafety *** outline the current cognitions upon oral microbes,engineered microbes and human cancers,related literatures were searched and reviewed based on the PubMed *** focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment,which involve in cancer occurrence and *** engineering oral bacteria can be a possible application of cancer therapy is worth consideration.A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.

关键词： prevention organs precise

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Genes & Diseases 2024年第3期11卷 66-68页

作者： Aswathi N Jincy M.Jose Sreelata B.Nair Prabha S.N Pappachan S department of medical {2. Lifeline Super Specialty HospitalPathanamthittaKerala 691523India Lifeline Super Specialty Hospital PathanamthittaKerala 691523India

Alagille syndrome(ALGS;OMIM#118450)is a highlyvariable,multi-systemic,autosomal dominant disorder,caused by mutations in the Jagged Canonical Notch Ligand 1(JAG1)gene(2.p12.2.or in the Neurogenic locus notch homolog protein 2.NOTCH2.gene(1p13).^(1)It primarily affects the liver,heart,eyes,face,kidney,skin,vertebrae,and skeleton.^(1,2.The JAG1 gene has 2. exons and about 90%of the ALGS cases result from pathogenic variants in the JAG1 and around 7%of cases have deletions in chromosome 2. that include this gene.

关键词： JAG1 cases Notch

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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

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Paroxysmal Kinesigenic Dyskinesia:genetics and Pathophysiological Mechanisms

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Neuroscience Bulletin 2024年第7期40卷 952-962页

作者： Jiao-Jiao Xu Hong-Fu Li Zhi-Ying Wu department of medical {2. and Center for Rare Diseases The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China department of Neurology in the Second Affiliated Hospital Key Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhou 310009China

Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary *** is mainly caused by mutations in the PRRT2.or TMEM151A *** exact pathophysiological mechanisms of PKD remain unclear,although the function of PRRT2.protein has been well characterized in the last *** on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2.PKD may be channelopathy or synaptopathy,or *** addition,the cerebellum is regarded as the key pathogenic *** depolarization in the cerebellum is tightly associated with dyskinetic ***,in PKD,other than the cerebellum,the role of the cerebrum including the cortex and thalamus needs to be further investigated.

关键词： Paroxysmal kinesigenic dyskinesia PRRT2 TMEM151A genetics Pathophysiological mechanisms

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