检索结果-南通市图书馆

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

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

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

Genome-wide studies Reveal Genetic Risk Factors for Hepatic Fat Content

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

Genomics, Proteomics & Bioinformatics 2024年第2期22卷 57-68页

作者： Yanni Li Eline H.van den Berg Alexander Kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu Esteban A.Lopera-Maya Alexandra Zhernakova Lifelines Cohort Study Vincent E.de Meijer Serena Sanna Robin P.F.Dullaart Hans Blokzijl Eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands department of genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China Laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands department of Endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands department of Pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical center Groningen(UMCG)genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and *** of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFLD Genome-wide association study Fatty liver index Magnetic resonance imaging proton density fat fraction

Both gain-and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of genetics and Genomics 2024年第8期51卷 801-810页

作者： Wan-Bing Sun Jing-Xin Fu Yu-Lan Chen Hong-Fu Li Zhi-Ying Wu Dian-Fu Chen department of Medical genetics and center for Rare Diseases and Department of Neurologyand Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation in Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Nanhu Brain-computer Interface Institute HangzhouZhejiang 314050China MOE Frontier Science center for Brain Science and Brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310012China

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channelα*** variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia(PKD),but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD *** the whole exome sequencing followed by Sanger sequencing,we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese *** proband of one family(c.496G>A,p.A166T)manifests as episodic ataxia type 1,and the other two(c.877G>A,p.V293I and c.1112C>A,p.T371A)manifest as *** pathogenicity of these variants is confirmed by functional studies,suggesting that p.A166T and p.T371A cause a loss-of-function of the channel,while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic *** reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein,we find that these variants tend to cluster around the pore domain,which is similar to ***,our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype–phenotype correlations of KCNA1 channelopathy.

关键词： Paroxysmal kinesigenic dyskinesia KCNA1 Loss-of-function Gain-of-function Channelopathy Episodicataxiatype1

APIR:Aggregating Universal Proteomics Database Search Algorithms for Peptide Identification with FDR Control

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Genomics, Proteomics & Bioinformatics 2024年第2期22卷 171-187页

作者： Yiling Elaine Chen Xinzhou Ge Kyla Woyshner MeiLu McDermott Antigoni Manousopoulou Scott B.Ficarro Jarrod A.Marto Kexin Li Leo David Wang Jingyi Jessica Li department of Statistics and Data Science University of CaliforniaLos AngelesCA 90095USA department of Immuno-Oncology Beckman Research InstituteCity of Hope National Medical CenterDuarteCA 91010USA department of Quantitative and Computational Biology University of Southern CaliforniaLos AngelesCA 90089USA department of Cancer Biology and Blais Proteomics center Dana-Farber Cancer InstituteDepartment of PathologyBrigham and Women’s Hospital and Harvard Medical SchoolBostonMA 02215USA department of Pediatrics City of Hope National Medical CenterDuarteCA 91010USA Bioinformatics Interdepartmental Program University of CaliforniaLos AngelesCA 90095USA department of Human genetics University of CaliforniaLos AngelesCA 90095USA department of Computational Medicine University of CaliforniaLos AngelesCA 90095USA department of Biostatistics University of CaliforniaLos AngelesCA 90095USA

Advances in mass spectrometry(MS)have enabled high-throughput analysis of proteomes in biological *** state-of-the-art MS data analysis relies on database search algorithms to quantify proteins by identifying peptide–spectrum matches(PSMs),which convert mass spectra to peptide *** database search algorithms use distinct search strategies and thus may identify unique ***,no existing approaches can aggregate all user-specified database search algorithms with a guaranteed increase in the number of identified peptides and a control on the false discovery rate(FDR).To fill in this gap,we proposed a statistical framework,Aggregation of Peptide Identification Results(APIR),that is universally compatible with all database search ***,under an FDR threshold,APIR is guaranteed to identify at least as many,if not more,peptides as individual database search algorithms *** of APIR on a complex proteomics standard dataset showed that APIR outpowers individual database search algorithms and empirically controls the *** data studies showed that APIR can identify disease-related proteins and post-translational modifications missed by some individual database search *** APIR framework is easily extendable to aggregating discoveries made by multiple algorithms in other high-throughput biomedical data analysis,e.g.,differential gene expression analysis on RNA sequencing *** APIR R package is available at https://***/yiling0210/APIR.

关键词： Shotgun proteomics Peptide–spectrum match Peptide identification Aggregation of lists FDR control

A perspective review on the biosynthesis of plant-based secondary metabolites and their application as potent drugs

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

BIOCELL 2024年第4期48卷 541-557页

作者： JHILAM PRAMANIK AKASH KUMAR SARVESH RUSTAGI MEHAK KATYAL SHEETAL THAKUR JUTISHNA BORA SUMIRA MALIK ANCHAL TREHAN NAYAN TALUKDAR PETR SLAMA department of Food Technology ITM UniversityGwaliorIndia department of Food Technology SRM UniversitySonipatIndia department of Food Technology Uttaranchal UniversityDehradunIndia department of Nutrition and Dietetics Manav Rachna International Institute of Research&Studies(MRIIRS)FaridabadIndia University Centre for Research and Development UIBTChandigarh UniversityMohaliIndia Amity institute of Biotechnology Amity UniversityJharkhandRanchiIndia department of Biotechnology University Center for Research&Development(UCRD)Chandigarh UniversityMohaliPunjabIndia department of Science Guru Nanak College of Pharmaceutical SciencesDehradunIndia Program of Biotechnology Faculty of ScienceAssam down town UniversityGuwahatiIndia department of Animal Morphology Physiology and GeneticsMendel University in BrnoBrnoCzech Republic

Many phytochemicals and their derived metabolites produced by plants are extensively employed in commercial goods,pharmaceutical products as well as in the environmental and medicalﬁ***,these secondary metabolites obtained from plants are in low amounts,and it is difﬁcult to synthesize them at the industrial *** these challenges,they may be utilized for a variety of medicinal products that are either available in the market or are being researched and *** metabolites are complex compounds that exhibit ***,under controlled conditions with elicitors,desired secondary metabolites may be produced from plant cell *** review emphasizes the various aspects of secondary metabolites including their types,synthesis,and applications as medicinal *** article aims to promote the use of plant secondary metabolites in the management and treatment of various diseases.

关键词： Secondary metabolites Medicinal plant Synthesis Health benefits

METTL14 downregulation drives S100A4^(+)monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2024年第5期9卷 2176-2192页

作者： Yue-fan Wang Wen-li Zhang Zhi-xuan Li Yue Liu Jian Tan Hao-zan Yin Zhi-chao Zhang Xian-jie Piao Min-hao Ruan Zhi-hui Dai Si-jie Wang Chen-yang Mu Ji-hang Yuan Shu-han Sun Hui Liu Fu Yang The Third department of Hepatic Surgery Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University200438 ShanghaiChina The department of Medical genetics Naval Medical University200433 ShanghaiChina Translational Medicine Research center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital100048 BeijingChina The department of Pharmaceutical Analysis School of PharmacyNaval Medical University200433 ShanghaiChina Key Laboratory of Biosafety Defense Ministry of Education200433 ShanghaiChina Shanghai Key Laboratory of Medical Biodefense 200433 ShanghaiChina

Without intervention,a considerable proportion of patients with metabolism‐associated fatty liver disease(MAFLD)will progress from simple steatosis to metabolism‐associated steatohepatitis(MASH),liver fibrosis,and even hepatocellular ***,the molecular mechanisms that control progressive MAFLD have yet to be fully ***,we unraveled that the expression of the N6-methyladenosine(m6A)methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD,whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation,liver injury,and ***,hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet(HFD).Notably,in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner,which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1^(+)Ccr2^(+)monocyte-derived macrophages(Mo-macs).In detail,Cx3cr1^(+)Ccr2^(+)Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells(HSCs)to promote liver *** experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1^(+)Ccr2^(+)*** of METTL14 or GLS2,or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and *** together,these findings indicate potential therapies for the treatment of MAFLD progression.

关键词： S100A4 MyD88 metabolism

Genetic variation in a heat shock transcription factor modulates cold tolerance in maize

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Molecular Plant 2024年第9期17卷 1423-1438页

作者： Lei Gao Lingling Pan Yiting Shi Rong Zeng Minze Li Zhuoyang Li Xuan Zhang Xiaoming Zhao Xinru Gong Wei Huang Xiaohong Yang Jinsheng Lai Jianru Zuo Zhizhong Gong Xiqing Wang Weiwei Jin Zhaobin Dong Shuhua Yang State Key Laboratory of Plant Environmental Resilience Frontiers Science Center for Molecular Design BreedingCollege of Biological SciencesCenter for Crop Functional Genomics and Molecular BreedingChina Agricultural UniversityBeijing 100193China State Key Laboratory of Maize Bio-breeding National Maize Improvement CenterFrontiers Science Center for Molecular Design BreedingDepartment of Plant Geneticsand BreedingChinaAgricultural UniversityBeijingChina State Key Laboratory of Plant Genomics and National Plant Gene Research center Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101China

Understanding how maize(Zea mays)responds to cold stress is crucial for facilitating breeding programs of cold-tolerant *** extensive utilization of the genome-wide association study(GWAs)approach for exploring favorable natural alleles associated with maize cold tolerance,few studies have successfully identified candidate genes that contribute to maize cold *** this study,we used a diverse panel of inbred maize lines collected from different germplasm sources to perform a GWAS on var-iations in the relative injured area of maize true leaves during cold stress-a trait very closely correlated with maize cold *** identified HsF21,which encodes a B-class heat shock transcription factor(HSF)that positively regulates cold tolerance at both the seedling and germination *** varia-tions in the promoter of the cold-tolerant HSF21Hap1 allele led to increased HSF21 expression under cold stress by inhibiting binding of the basic leucine zipper bziP68 transcription factor,a negative regulator of cold *** integrating transcriptome deep sequencing,DNA affinity purification sequencing,and targeted lipidomic analysis,we revealed the function of HsF21 in regulating lipid metabolism homeo-stasis to modulate cold tolerance in *** addition,we found that HsF21 confers maize cold tolerance without incurring yield ***,this study establishes HsF21 as a key regulator that en-hances cold tolerance in maize,providing valuable genetic resources for breeding of cold-tolerant maize varieties.

关键词： heat shock factor HSF21 cold tolerance natural variation bZiP68 lipid metabolism maize

Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2024年第3期9卷 1199-1208页

作者： Xinyi Yang Xu Zheng Yuqi Zhu Xiaying Zhao Jun Liu Jiangna Xun Songhua Yuan Jun Chen Hanyu Pan Jinlong Yang Jing Wang Zhimin Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Min Li Fei Peng Daru Lu Jianqing Xu Hongzhou Lu Shibo Jiang Ping Zhao Huanzhang Zhu State Key Laboratory of Genetic Engineering and Engineering Research center of Gene Technology Ministry of EducationInstitute of GeneticsSchool of Life SciencesYiwu Research InstituteFudan UniversityShanghaiChina department of Microbiology Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Scientific Research center Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina department of Infectious Diseases and Immunology Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Changzheng Hospital Naval Medical UniversityShanghaiChina Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghaiChina department of Infectious Diseases and Nursing Research Institution National Clinical Research Center for Infectious DiseasesThe Third People’s Hospital of ShenzhenShenzhenGuangdongChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)causes multi-organ damage,which includes hepatic dysfunction,as observed in over 50%of COVID-19 *** I converting enzyme(peptidyl-dipeptidase A)2(ACE2)is the primary receptor for SARS-CoV-2 entry into host cells,and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2,but at extremely low ***,we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into *** address this question,we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1(ASGR1)promoted SARS-CoV-2 pseudovirus infection of HeLa *** Huh-7 cells,simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus *** the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells,both of which barely expressed ACE2,SARSCoV-2 pseudovirus could successfully establish an ***,after treatment with ASGR1 antibody or siRNA targeting ASGR1,the infection rate significantly dropped,suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent *** confirmed that ASGR1 could interact with Spike protein,which depends on receptor binding domain(RBD)and N-terminal domain(NTD).Finally,we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal *** inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA,the infection efficiency of the live virus decreased ***,these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.

关键词： ACE2 infection glycoprotein

Targeting miRNA by CRISPR/Cas in cancer:advantages and challenges

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Military Medical Research 2024年第3期11卷 345-373页

作者： Bashdar Mahmud Hussen Mohammed Fatih Rasul Snur Rasool Abdullah Hazha Jamal Hidayat Goran Sedeeq Hama Faraj Fattma Abodi Ali Abbas Salihi Aria Baniahmad Soudeh Ghafouri-Fard Milladur Rahman Mark C.Glassy Wojciech Branicki Mohammad Taheri department of Biomedical Sciences Cihan University-ErbilErbilKurdistan Region 44001Iraq department of Clinical Analysis College of PharmacyHawler Medical UniversityErbilKurdistan Region 44001Iraq department of Pharmaceutical Basic Science Faculty of PharmacyTishk International UniversityErbilKurdistan Region 44001Iraq Medical Laboratory Science Lebanese French UniversityErbilKurdistan Region 44001Iraq department of Biology College of EducationSalahaddin University-ErbilErbilKurdistan Region 44001Iraq department of Medical Laboratory Science Komar University of Science and TechnologySulaymaniyah 46001Iraq department of Medical Microbiology College of Health SciencesHawler Medical UniversityErbilKurdistan Region 44001Iraq department of Biology College of ScienceSalahaddin University-ErbilErbilKurdistan Region 44001Iraq center of Research and Strategic studies Lebanese French UniversityErbil 44001Iraq Institute of Human genetics Jena University Hospital07747 JenaGermany department of Medical genetics School of MedicineShahid Beheshti University of Medical SciencesTehran 374-37515Iran department of Clinical Sciences MalmöSection for SurgeryLund University22100 MalmöSweden Translational Neuro-Oncology Laboratory San Diego(UCSD)Moores Cancer CenterUniversity of CaliforniaSan DiegoCA 94720USA Faculty of Biology Institute of Zoology and Biomedical ResearchJagiellonian University31-007 KrakówPoland Urology and Nephrology Research center Shahid Beheshti University of Medical SciencesTehran 374-37515Iran

Clustered regulatory interspaced short palindromic repeats(CRISPR)has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last *** the study of cancer,the CRISPR/CRISPR-associated protein(Cas)system opens new avenues into issues that were once unknown in our knowledge of the non-coding genome,tumor heterogeneity,and precision ***/Cas-based geneediting technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs(miRNAs).However,the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other *** study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer ***,we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them.

关键词： CRISPR CRISPR/Cas9 CRISPR/Cas12 Gene editing miRNAs Cancer therapy