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信号转导与靶向治疗(英文)
信号转导与靶向治疗(英文)
信号转导与靶向治疗(英文)/Journal Signal Transduction and Targeted TherapyCSTPCDSCI
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    TransTACs:novel heterobispecific antibodies for targeted protein degradation in cancer therapy

    Wolfgang WaltherSebastian TorkeUlrike Stein
    5370-5372页

    Ischemic stroke is an instigator of cardiac dysfunction:the interleukin-1β pathway

    Renate Schoenenberger-BerzinsAndreas Janis SchoenenbergerFranz H.Messerli
    5373-5374页

    Tissue fluidity:biophysical shape-shifting for regeneration

    Zitong CZhenyu CY.Rinkevich
    5375-5376页

    Unraveling the RNA code:a uridine RNA modification drives glycoRNA biogenesis

    Marco SachseKonstantinos Stellos
    5377-5378页

    Human olfaction:odour coding and cross-modal concept representation in single olfactory cortex neurons

    Antonia BeiersdorferMarkus RothermelChristian Lohr
    5379-5380页

    Dietary restriction interventions:lifespan benefits need resilience and are limited by immune compromise and genetics

    Yulin ChenAnjalika MalikKarl Lenhard Rudolph
    5381-5382页

    A comprehensive proteomic analysis of umbilical cord blood supports COVID-19 vaccination before pregnancy

    Jianbin GuoXiaoyue TangRoujie HuangJiangfeng Liu...
    5383-5385页

    Targeted protein degradation:advances in drug discovery and clinical practice

    Guangcai ZhongXiaoyu ChangWeilin XieXiangxiang Zhou...
    5386-5430页
    查看更多>>摘要:Targeted protein degradation(TPD)represents a revolutionary therapeutic strategy in disease management,providing a stark contrast to traditional therapeutic approaches like small molecule inhibitors that primarily focus on inhibiting protein function.This advanced technology capitalizes on the cell's intrinsic proteolytic systems,including the proteasome and lysosomal pathways,to selectively eliminate disease-causing proteins.TPD not only enhances the efficacy of treatments but also expands the scope of protein degradation applications.Despite its considerable potential,TPD faces challenges related to the properties of the drugs and their rational design.This review thoroughly explores the mechanisms and clinical advancements of TPD,from its initial conceptualization to practical implementation,with a particular focus on proteolysis-targeting chimeras and molecular glues.In addition,the review delves into emerging technologies and methodologies aimed at addressing these challenges and enhancing therapeutic efficacy.We also discuss the significant clinical trials and highlight the promising therapeutic outcomes associated with TPD drugs,illustrating their potential to transform the treatment landscape.Furthermore,the review considers the benefits of combining TPD with other therapies to enhance overall treatment effectiveness and overcome drug resistance.The future directions of TPD applications are also explored,presenting an optimistic perspective on further innovations.By offering a comprehensive overview of the current innovations and the challenges faced,this review assesses the transformative potential of TPD in revolutionizing drug development and disease management,setting the stage for a new era in medical therapy.

    Comprehensive snapshots of natural killer cells functions,signaling,molecular mechanisms and clinical utilization

    Sumei ChenHaitao ZhuYoussef Jounaidi
    5431-5469页
    查看更多>>摘要:Natural killer(NK)cells,initially identified for their rapid virus-infected and leukemia cell killing and tumor destruction,are pivotal in immunity.They exhibit multifaceted roles in cancer,viral infections,autoimmunity,pregnancy,wound healing,and more.Derived from a common lymphoid progenitor,they lack CD3,B-cell,or T-cell receptors but wield high cytotoxicity via perforin and granzymes.NK cells orchestrate immune responses,secreting inflammatory IFNγ or immunosuppressive TGFβ and IL-10.CD56dim and CD56bright NK cells execute cytotoxicity,while CD56bright cells also regulate immunity.However,beyond the CD56 dichotomy,detailed phenotypic diversity reveals many functional subsets that may not be optimal for cancer immunotherapy.In this review,we provide comprehensive and detailed snapshots of NK cells'functions and states of activation and inhibitions in cancer,autoimmunity,angiogenesis,wound healing,pregnancy and fertility,aging,and senescence mediated by complex signaling and ligand-receptor interactions,including the impact of the environment.As the use of engineered NK cells for cancer immunotherapy accelerates,often in the footsteps of T-cell-derived engineering,we examine the interactions of NK cells with other immune effectors and relevant signaling and the limitations in the tumor microenvironment,intending to understand how to enhance their cytolytic activities specifically for cancer immunotherapy.

    Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications

    Yingying ShiMeixing ShiYi WangJian You...
    5470-5512页
    查看更多>>摘要:In the last decade,messenger ribonucleic acid(mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications.This surge in interest can be largely attributed to the demonstration of distinct advantages offered by various mRNA molecules,alongside the rapid advancements in nucleic acid delivery systems.It is noteworthy that the immunogenicity of mRNA drugs presents a double-edged sword.In the context of immunotherapy,extra supplementation of adjuvant is generally required for induction of robust immune responses.Conversely,in non-immunotherapeutic scenarios,immune activation is unwanted considering the host tolerability and high expression demand for mRNA-encoded functional proteins.Herein,mainly focused on the linear non-replicating mRNA,we overview the preclinical and clinical progress and prospects of mRNA medicines encompassing vaccines and other therapeutics.We also highlight the importance of focusing on the host-specific variations,including age,gender,pathological condition,and concurrent medication of individual patient,for maximized efficacy and safety upon mRNA administration.Furthermore,we deliberate on the potential challenges that mRNA drugs may encounter in the realm of disease treatment,the current endeavors of improvement,as well as the application prospects for future advancements.Overall,this review aims to present a comprehensive understanding of mRNA-based therapies while illuminating the prospective development and clinical application of mRNA drugs.