首页期刊导航|信号转导与靶向治疗(英文)
期刊信息/Journal information
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
正式出版
收录年代

    Innate immune sensing of danger signals:novel mechanism of heme complex-mediated lytic cell death

    Chintan ChhatbarMichael SchulzRoman Sankowski
    4175-4177页

    Circulating tumor cells:from new biological insights to clinical practice

    Xuyu GuShiyou WeiXin Lv
    4178-4212页
    查看更多>>摘要:The primary reason for high mortality rates among cancer patients is metastasis,where tumor cells migrate through the bloodstream from the original site to other parts of the body.Recent advancements in technology have significantly enhanced our comprehension of the mechanisms behind the bloodborne spread of circulating tumor cells(CTCs).One critical process,DNA methylation,regulates gene expression and chromosome stability,thus maintaining dynamic equilibrium in the body.Global hypomethylation and locus-specific hypermethylation are examples of changes in DNA methylation patterns that are pivotal to carcinogenesis.This comprehensive review first provides an overview of the various processes that contribute to the formation of CTCs,including epithelial-mesenchymal transition(EMT),immune surveillance,and colonization.We then conduct an in-depth analysis of how modifications in DNA methylation within CTCs impact each of these critical stages during CTC dissemination.Furthermore,we explored potential clinical implications of changes in DNA methylation in CTCs for patients with cancer.By understanding these epigenetic modifications,we can gain insights into the metastatic process and identify new biomarkers for early detection,prognosis,and targeted therapies.This review aims to bridge the gap between basic research and clinical application,highlighting the significance of DNA methylation in the context of cancer metastasis and offering new avenues for improving patient outcomes.

    Sex difference in human diseases:mechanistic insights and clinical implications

    Yuncong ShiJianshuai MaSijin LiChao Liu...
    4213-4245页
    查看更多>>摘要:Sex characteristics exhibit significant disparities in various human diseases,including prevalent cardiovascular diseases,cancers,metabolic disorders,autoimmune diseases,and neurodegenerative diseases.Risk profiles and pathological manifestations of these diseases exhibit notable variations between sexes.The underlying reasons for these sex disparities encompass multifactorial elements,such as physiology,genetics,and environment.Recent studies have shown that human body systems demonstrate sex-specific gene expression during critical developmental stages and gene editing processes.These genes,differentially expressed based on different sex,may be regulated by androgen or estrogen-responsive elements,thereby influencing the incidence and presentation of cardiovascular,oncological,metabolic,immune,and neurological diseases across sexes.However,despite the existence of sex differences in patients with human diseases,treatment guidelines predominantly rely on male data due to the underrepresentation of women in clinical trials.At present,there exists a substantial knowledge gap concerning sex-specific mechanisms and clinical treatments for diverse diseases.Therefore,this review aims to elucidate the advances of sex differences on human diseases by examining epidemiological factors,pathogenesis,and innovative progress of clinical treatments in accordance with the distinctive risk characteristics of each disease and provide a new theoretical and practical basis for further optimizing individualized treatment and improving patient prognosis.

    Emerging and reemerging infectious diseases:global trends and new strategies for their prevention and control

    Shen WangWujian LiZhenshan WangWanying Yang...
    4246-4313页
    查看更多>>摘要:To adequately prepare for potential hazards caused by emerging and reemerging infectious diseases,the WHO has issued a list of high-priority pathogens that are likely to cause future outbreaks and for which research and development(R&D)efforts are dedicated,known as paramount R&D blueprints.Within R&D efforts,the goal is to obtain effective prophylactic and therapeutic approaches,which depends on a comprehensive knowledge of the etiology,epidemiology,and pathogenesis of these diseases.In this process,the accessibility of animal models is a priority bottleneck because it plays a key role in bridging the gap between in-depth understanding and control efforts for infectious diseases.Here,we reviewed preclinical animal models for high priority disease in terms of their ability to simulate human infections,including both natural susceptibility models,artificially engineered models,and surrogate models.In addition,we have thoroughly reviewed the current landscape of vaccines,antibodies,and small molecule drugs,particularly hopeful candidates in the advanced stages of these infectious diseases.More importantly,focusing on global trends and novel technologies,several aspects of the prevention and control of infectious disease were discussed in detail,including but not limited to gaps in currently available animal models and medical responses,better immune correlates of protection established in animal models and humans,further understanding of disease mechanisms,and the role of artificial intelligence in guiding or supplementing the development of animal models,vaccines,and drugs.Overall,this review described pioneering approaches and sophisticated techniques involved in the study of the epidemiology,pathogenesis,prevention,and clinical theatment of WHO high-priority pathogens and proposed potential directions.Technological advances in these aspects would consolidate the line of defense,thus ensuring a timely response to WHO high priority pathogens.

    Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges

    Yunlong ShanMengying ZhangEnxiang TaoJing Wang...
    4314-4340页
    查看更多>>摘要:Over the past two decades,mesenchymal stem/stromal cell(MSC)therapy has made substantial strides,transitioning from experimental clinical applications to commercial products.MSC therapies hold considerable promise for treating refractory and critical conditions such as acute graft-versus-host disease,amyotrophic lateral sclerosis,and acute respiratory distress syndrome.Despite recent successes in clinical and commercial applications,MSC therapy still faces challenges when used as a commercial product.Current detection methods have limitations,leaving the dynamic biodistribution,persistence in injured tissues,and ultimate fate of MSCs in patients unclear.Clarifying the relationship between the pharmacokinetic characteristics of MSCs and their therapeutic effects is crucial for patient stratification and the formulation of precise therapeutic regimens.Moreover,the development of advanced imaging and tracking technologies is essential to address these clinical challenges.This review provides a comprehensive analysis of the kinetic properties,key regulatory molecules,different fates,and detection methods relevant to MSCs and discusses concerns in evaluating MSC druggability from the perspective of integrating pharmacokinetics and efficacy.A better understanding of these challenges could improve MSC clinical efficacy and speed up the introduction of MSC therapy products to the market.

    Crossing epigenetic frontiers:the intersection of novel histone modifications and diseases

    Weiyi YaoXinting HuXin Wang
    4341-4378页
    查看更多>>摘要:Histone post-translational modifications(HPTMs),as one of the core mechanisms of epigenetic regulation,are garnering increasing attention due to their close association with the onset and progression of diseases and their potential as targeted therapeutic agents.Advances in high-throughput molecular tools and the abundance of bioinformatics data have led to the discovery of novel HPTMs which similarly affect gene expression,metabolism,and chromatin structure.Furthermore,a growing body of research has demonstrated that novel histone modifications also play crucial roles in the development and progression of various diseases,including various cancers,cardiovascular diseases,infectious diseases,psychiatric disorders,and reproductive system diseases.This review defines nine novel histone modifications:lactylation,citrullination,crotonylation,succinylation,SUMOylation,propionylation,butyrylation,2-hydroxyisobutyrylation,and 2-hydroxybutyrylation.It comprehensively introduces the modification processes of these nine novel HPTMs,their roles in transcription,replication,DNA repair and recombination,metabolism,and chromatin structure,as well as their involvement in promoting the occurrence and development of various diseases and their clinical applications as therapeutic targets and potential biomarkers.Moreover,this review provides a detailed overview of novel HPTM inhibitors targeting various targets and their emerging strategies in the treatment of multiple diseases while offering insights into their future development prospects and challenges.Additionally,we briefly introduce novel epigenetic research techniques and their applications in the field of novel HPTM research.

    Glucagon-like peptide-1 receptor:mechanisms and advances in therapy

    Zhikai ZhengYao ZongYiyang MaYucheng Tian...
    4379-4407页
    查看更多>>摘要:The glucagon-like peptide-1(GLP-1)receptor,known as GLP-1R,is a vital component of the G protein-coupled receptor(GPCR)family and is found primarily on the surfaces of various cell types within the human body.This receptor specifically interacts with GLP-1,a key hormone that plays an integral role in regulating blood glucose levels,lipid metabolism,and several other crucial biological functions.In recent years,GLP-1 medications have become a focal point in the medical community due to their innovative treatment mechanisms,significant therapeutic efficacy,and broad development prospects.This article thoroughly traces the developmental milestones of GLP-1 drugs,from their initial discovery to their clinical application,detailing the evolution of diverse GLP-1 medications along with their distinct pharmacological properties.Additionally,this paper explores the potential applications of GLP-1 receptor agonists(GLP-1 RAs)in fields such as neuroprotection,anti-infection measures,the reduction of various types of inflammation,and the enhancement of cardiovascular function.It provides an in-depth assessment of the effectiveness of GLP-1 RAs across multiple body systems-including the nervous,cardiovascular,musculoskeletal,and digestive systems.This includes integrating the latest clinical trial data and delving into potential signaling pathways and pharmacological mechanisms.The primary goal of this article is to emphasize the extensive benefits of using GLP-1 RAs in treating a broad spectrum of diseases,such as obesity,cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),neurodegenerative diseases,musculoskeletal inflammation,and various forms of cancer.The ongoing development of new indications for GLP-1 drugs offers promising prospects for further expanding therapeutic interventions,showcasing their significant potential in the medical field.

    Neutrophil extracellular traps in homeostasis and disease

    Han WangSusan J.KimYu LeiShuhui Wang...
    4408-4447页
    查看更多>>摘要:Neutrophil extracellular traps(NETs),crucial in immune defense mechanisms,are renowned for their propensity to expel decondensed chromatin embedded with inflammatory proteins.Our comprehension of NETs in pathogen clearance,immune regulation and disease pathogenesis,has grown significantly in recent years.NETs are not only pivotal in the context of infections but also exhibit significant involvement in sterile inflammation.Evidence suggests that excessive accumulation of NETs can result in vessel occlusion,tissue damage,and prolonged inflammatory responses,thereby contributing to the progression and exacerbation of various pathological states.Nevertheless,NETs exhibit dual functionalities in certain pathological contexts.While NETs may act as autoantigens,aggregated NET complexes can function as inflammatory mediators by degrading proinflammatory cytokines and chemokines.The delineation of molecules and signaling pathways governing NET formation aids in refining our appreciation of NETs'role in immune homeostasis,inflammation,autoimmune diseases,metabolic dysregulation,and cancer.In this comprehensive review,we delve into the multifaceted roles of NETs in both homeostasis and disease,whilst discussing their potential as therapeutic targets.Our aim is to enhance the understanding of the intricate functions of NETs across the spectrum from physiology to pathology.

    Pyroptosis in health and disease:mechanisms,regulation and clinical perspective

    Yifan LiuRenjie PanYuzhen OuyangWangning Gu...
    4448-4475页
    查看更多>>摘要:Pyroptosis is a type of programmed cell death characterized by cell swelling and osmotic lysis,resulting in cytomembrane rupture and release of immunostimulatory components,which play a role in several pathological processes.Significant cellular responses to various stimuli involve the formation of inflammasomes,maturation of inflammatory caspases,and caspase-mediated cleavage of gasdermin.The function of pyroptosis in disease is complex but not a simple angelic or demonic role.While inflammatory diseases such as sepsis are associated with uncontrollable pyroptosis,the potent immune response induced by pyroptosis can be exploited as a therapeutic target for anti-tumor therapy.Thus,a comprehensive review of the role of pyroptosis in disease is crucial for further research and clinical translation from bench to bedside.In this review,we summarize the recent advancements in understanding the role of pyroptosis in disease,covering the related development history,molecular mechanisms including canonical,non-canonical,caspase 3/8,and granzyme-mediated pathways,and its regulatory function in health and multiple diseases.Moreover,this review also provides updates on promising therapeutic strategies by applying novel small molecule inhibitors and traditional medicines to regulate pyroptosis.The present dilemmas and future directions in the landscape of pyroptosis are also discussed from a clinical perspective,providing clues for scientists to develop novel drugs targeting pyroptosis.

    A systematic framework for understanding the microbiome in human health and disease:from basic principles to clinical translation

    Ziqi MaTao ZuoNorbert FreyAshraf Yusuf Rangrez...
    4476-4511页
    查看更多>>摘要:The human microbiome is a complex and dynamic system that plays important roles in human health and disease.However,there remain limitations and theoretical gaps in our current understanding of the intricate relationship between microbes and humans.In this narrative review,we integrate the knowledge and insights from various fields,including anatomy,physiology,immunology,histology,genetics,and evolution,to propose a systematic framework.It introduces key concepts such as the'innate and adaptive genomes',which enhance genetic and evolutionary comprehension of the human genome.The'germ-free syndrome'challenges the traditional'microbes as pathogens'view,advocating for the necessity of microbes for health.The'slave tissue'concept underscores the symbiotic intricacies between human tissues and their microbial counterparts,highlighting the dynamic health implications of microbial interactions.'Acquired microbial immunity'positions the microbiome as an adjunct to human immune systems,providing a rationale for probiotic therapies and prudent antibiotic use.The'homeostatic reprogramming hypothesis'integrates the microbiome into the internal environment theory,potentially explaining the change in homeostatic indicators post-industrialization.The'cell-microbe co-ecology model'elucidates the symbiotic regulation affecting cellular balance,while the'meta-host model'broadens the host definition to include symbiotic microbes.The'health-illness conversion model'encapsulates the innate and adaptive genomes'interplay and dysbiosis patterns.The aim here is to provide a more focused and coherent understanding of microbiome and highlight future research avenues that could lead to a more effective and efficient healthcare system.