检索结果-南通市图书馆

Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

Acta Pharmaceutica Sinica B 2024年第1期14卷 67-86页

作者： Chunhao Zhu Xiaobing Lan Zhiqiang Wei Jianqiang Yu Jian Zhang School of Pharmacy Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and bioinformatics center Shanghai Jiao Tong University School of MedicineShanghai 200025China School of Basic Medical Science Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and bioinformatics center Ocean University of ChinaQingdao 266100China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical ***,current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse *** G protein-coupled receptors(GPCRs)are widely distributed throughout the body,including the pain transmission pathway and descending inhibition pathway,the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining *** research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse *** review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain,and discuss the potential benefits and adverse factors of this *** will also concentrate on the development of biased agonists of GPCRs,and based on important examples of biased agonist development in recent years,we will describe universal strategies for designing structure-based biased *** is foreseeable that,with the continuous improvement of GPCRs allosteric modulation and biased agonist theory,effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

关键词： Neuropathic pain Allosteric modulators G protein-coupled receptors Analgesia

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

Genetic landscape and clinical significance of cuproptosis-related genes in liver hepatocellular carcinoma

引用

Genes & Diseases 2024年第2期11卷 516-519页

作者： Dingtao Hu Yichuan Wang Xu Shen Tiantian Mao Xijun Liang Tengjiao Wang Weifeng Shen Yugang Zhuang Jin Ding Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghai 200433China Department of Emergency Shanghai Tenth People's HospitalTongji UniversitySchool of MedicineShanghai 200072China bioinformatics Analysis Laboratory Center for Translational MedicineNaval Medical UniversityShanghai 200433China The Department of Hepatic Surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China

Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in *** then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical *** detailed methods were described in the supplementary material.

关键词： clinical metabolism hepatocellular

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

G protein-coupled receptors(GPCRs):advances in structures,mechanisms,and drug discovery

引用

Signal Transduction and Targeted Therapy 2024年第5期9卷 1938-1980页

作者： Mingyang Zhang Ting Chen Xun Lu Xiaobing Lan Ziqiang Chen Shaoyong Lu Key Laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China Medicinal Chemistry and bioinformatics center Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Cardiology Changzheng HospitalAffiliated to Naval Medical UniversityShanghai 200003China Department of Orthopedics Changhai HospitalAffiliated to Naval Medical UniversityShanghai 200433China

G protein-coupled receptors(GPCRs),the largest family of human membrane proteins and an important class of drug targets,play a role in maintaining numerous physiological *** or antagonist,orthosteric effects or allosteric effects,and biased signaling or balanced signaling,characterize the complexity of GPCR dynamic *** this study,we first review the structural advancements,activation mechanisms,and functional diversity of *** then focus on GPCR drug discovery by revealing the detailed drug-target interactions and the underlying mechanisms of orthosteric drugs approved by the US Food and Drug Administration in the past five ***,an up-to-date analysis is performed on available GPCR structures complexed with synthetic small-molecule allosteric modulators to elucidate key receptor-ligand interactions and allosteric ***,we highlight how the widespread GPCR-druggable allosteric sites can guide structure-or mechanism-based drug design and propose prospects of designing bitopic ligands for the future therapeutic potential of targeting this receptor family.

关键词： steric designing mechanisms

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

Multi-omics integration reveals potential stage-specific druggable targets in T-cell acute lymphoblastic leukemia

引用

Genes & Diseases 2024年第5期11卷 374-389页

作者： Zijun Yan Jie Xia Ziyang Cao Hongyang Zhang Jinxia Wang Tienan Feng Yi Shu Lin Zou Clinical Research Unit Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Institute of Pediatric Infection Immunityand Critical Care MedicineShanghai Jiao Tong University School of MedicineShanghai 200062China center for Clinical Molecular Laboratory Medicine of Children’s Hospital of Chongqing Medical University Chongqing 400014China Clinical Research Institute Shanghai Jiao Tong University School of MedicineShanghai 200025China bioinformatics and BioMedical Bigdata Mining Laboratory School of Big HealthGuizhou Medical UniversityGuiyangGuizhou 554300China

T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell *** development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this *** this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this *** multi-omics integration helped identify 29 potential pathological genes for *** genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling *** these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in *** TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive ***6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation ***,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in ***,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.

关键词： Multi-omics Stage-specific druggable targets Targeted therapeutic strategies T-cell acute lymphoblastic leukemia Drug repositioning

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

SPATULA as a Versatile Tool in Plant:The Progress and Perspectives of SPATULA(SPT)Transcriptional Factor

引用

Phyton-International Journal of Experimental Botany 2024年第3期93卷 517-531页

作者： Lei Liang Xiangyang Hu shanghai Key Laboratory of Bio-Energy Crops Research Center for Natural ProductsPlant Science CenterSchool of Life SciencesShanghai UniversityShanghai200444China

With the rapid development of modern molecular biology and bioinformatics,many studies have proved that transcription factors play an important role in regulating the growth and development of ***(SPT)belongs to the bHLH transcription family and participates in many processes of regulating plant growth and *** review systemically summarizes the multiple roles of SPT in plant growth,development,and stress response,including seed germination,ﬂowering,leaf size,carpel development,and root elongation,which is helpful for us to better understand the functions of SPT.

关键词： SPT bHLH plant growth plant development Arabidopsis thaliana

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

Computer-aided molecular design and optimization of potent inhibitors disrupting APC-Asef interaction

引用

Acta Pharmaceutica Sinica B 2024年第6期14卷 2631-2645页

作者： Xuefei Wang Zeqian Du Yuegui Guo Jie Zhong Kun Song Junyuan Wang Jianqiang Yu Xiuyan Yang Chen-Ying Liu Ting Shi Jian Zhang Department of Pathophysiology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China Key Laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China State Key Laboratory of Microbial Metabolism Joint International Research Laboratory of Metabolic and Developmental SciencesSchool of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China Department of Colorectal and Anal Surgery Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Basic Science Research center Base(Pharmaceutical Science) Yantai UniversityYantai 264005China Medicinal Chemistry and bioinformatics center Shanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Colorectal cancer(CRC)is the second leading cause of cancer mortality *** initial diagnosis,approximately 20%of patients are diagnosed with metastatic CRC(mCRC).Although the APC-Asef interaction is a well-established target for mCRC therapy,the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging *** this study,we identified a novel structural scaffold based on MAI inhibitors,the first-in-class APC-Asef inhibitors we reported *** model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed,and 24-fold greater potency was obtained with the best inhibitor compared to the parental *** addition,the cocrystal structure validated that the two-layerπ-πstacking interactions were essential for inhibitor stabilization in the bound ***,in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC-Asef *** results provide an intrinsic structural basis to further explore drug-like molecules for APC-Asef-mediated CRC therapy.

关键词： APC-Asef Peptidomimetic Computer-aided molecular design ONIOM model π-πstacking Metastatic colorectal cancer

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

PICOTEES:a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants from Chinese children cohorts

引用

Journal of Genetics and Genomics 2024年第2期51卷 243-251页

作者： Xinran Dong Yulan Lu Lanting Guo Chuan Li Qi Ni Bingbing Wu Huijun Wang Lin Yang Songyang Wu Qi Sun Hao Zheng Wenhao Zhou Shuang Wang center for Molecular Medicine Children's Hospital of Fudan UniversityShanghai 201102China Key Laboratory of Birth Defects Children's Hospital of Fudan UniversityShanghai 201102China Department of bioinformatics Hangzhou Nuowei Information Technology Co.LtdHangzhouZhejiang 310000China The Third Research Institute of the Ministry of Public Security Shanghai 200031China Xiamen Campus of Children's Hospital of Fudan University XiamenFujian 361006China Institutes for Systems Genetics West China HospitalChengduSichuan 610041China shanghai Putuo People's Hospital Tongji UniversityShanghai 200060China

The growth in biomedical data resources has raised potential privacy concerns and risks of genetic information leakage. For instance, exome sequencing aids clinical decisions by comparing data through web services, but it requires significant trust between users and providers. To alleviate privacy concerns, the most commonly used strategy is to anonymize sensitive data. Unfortunately, studies have shown that anonymization is insufficient to protect against reidentification attacks. Recently, privacy-preserving technologies have been applied to preserve application utility while protecting the privacy of biomedical data. We present the PICOTEES framework, a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants (https://***:3000/). PICOTEES enables privacy-preserving queries of the phenotype spectrum for a single variant by utilizing trusted execution environment technology, which can protect the privacy of the user's query information, backend models, and data, as well as the final results. We demonstrate the utility and performance of PICOTEES by exploring a bioinformatics dataset. The dataset is from a cohort containing 20,909 genetic testing patients with 3,152,508 variants from the Children's Hospital of Fudan University in China, dominated by the Chinese Han population (>99.9%). Our query results yield a large number of unreported diagnostic variants and previously reported pathogenicity.

关键词： Privacy protecti on Rare diseases in children Genetic testing Web system Trusted executi on envir onment

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

scRNA-seq reveals that origin recognition complex subunit 6 regulates mouse spermatogonial cell proliferation and apoptosis via activation of Wnt/β-catenin signaling

引用

Asian Journal of Andrology 2024年第1期26卷 46-56页

作者： Shi-Wei Liu Jia-Qiang Luo Liang-Yu Zhao Ning-Jing Ou Chao-Yang Yu-Xiang Zhang Hao-Wei Bai Hong-Fang Sun Jian-Xiong Zhang Chen-Cheng Yao Peng Li Ru-Hui Tian Zheng Li Zi-Jue Zhu Department of Andrology Center for Men's HealthUrologic Medical CenterShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China State Key Lab of Reproductive Medicine Nanjing Medical UniversityNanjing 211166China shanghai Key Lab of Reproductive Medicine Shanghai Jiao Tong University School of MedicineShanghai 200080China Department of Urology Guangdong Provincial Key Laboratory of Biomedical ImagingThe Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China Department of Urology First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining *** single-cell RNA sequencing(scRNA-seq)analysis of the testis was performed to identify genes upregulated in *** scRNAseq analysis,we identified the spermatogonia upregulated gene origin recognition complex subunit 6(Orc6),which is involved in DNA replication and cell cycle regulation;its protein expression in the human and mouse testis was detected by western blot and *** explore the potential function of Orc6 in spermatogonia,the C18-4 cell line was transfected with control or Orc6 ***,5-ethynyl-2-deoxyuridine(EdU)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays,flow cytometry,and western blot were used to evaluate its effects on proliferation and *** was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 *** RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated(Wnt)/β-catenin *** blot revealed that the expression ofβ-catenin protein and its phosphorylation(Ser675)were significantly decreased when silencing the expression of *** findings indicated that Orc6 was upregulated in spermatogonia,whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

关键词： cell proliferation ORCG scRNA-seq analysis spermatogonia Wnt/β-catenin signaling

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

DNA bridging of FOXP3 ladder-like multimer: Unveiling a novel transcriptional regulation paradigm

引用

The Innovation 2024年第3期5卷 15-16页

作者： Ying Lu Lanfang Li Hanting Yang Bin Li Zuoyun Wang Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education Shanghai Xuhui Central Hospital and School of Basic Medical SciencesFudan UniversityShanghai 200032China Institute for Translational Brain Research State Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain ScienceDepartment of NeurologyZhongshan HospitalFudan UniversityShanghai 200032China center for Immune-Related Diseases at shanghai Institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai 200025China

In the latest issue of Nature,Zhang et *** a novel ladder-like structure of FOXP3-DNA interaction involving FOXP3 multimerization and remote DNA bridging through a combination of biochemistry,structural biology,cell biology,and bioinformatics analyses.1 In this commentary,we highlight their key findings and provide our insights into the research paradigm for further exploration of a novel transcriptional regulation mode as well as a therapeutic strategy from the structural aspects of the FOXP3 complex(Figure 1).

关键词： FOXP3 bridging

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

Foundation models in molecular biology

引用

Biophysics Reports 2024年第3期10卷 135-151页

作者： Yunda Si Jiawei Zou Yicheng Gao Guohui Chuai Qi Liu Luonan Chen Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Chinese Academy of Sciences shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences University of Chinese Academy of Sciences Translational Medical center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East Hospital Frontier Science Center for Stem Cell Research Bioinformatics Department School of Life Sciences and Technology Tongji University shanghai Research Institute for Intelligent Autonomous Systems

Determining correlations between molecules at various levels is an important topic in molecular biology. Large language models have demonstrated a remarkable ability to capture correlations from large amounts of data in the field of natural language processing as well as image generation, and correlations captured from data using large language models can also be applicable to solving a wide range of specific tasks, hence large language models are also referred to as foundation models. The massive amount of data that exists in the field of molecular biology provides an excellent basis for the development of foundation models, and the recent emergence of foundation models in the field of molecular biology has really pushed the entire field forward. We summarize the foundation models developed based on RNA sequence data, DNA sequence data, protein sequence data, single-cell transcriptome data, and spatial transcriptome data respectively, and further discuss the research directions for the development of foundation models in molecular biology.

关键词： Foundation models Molecular biology Transcriptome

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：