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Targeting dendritic cells to drive PDAC immunotherapy response. 靶向树突状细胞驱动 PDAC 免疫疗法反应。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI: 10.1016/j.tips.2024.10.009
Alyssa G Weinstein, David G DeNardo
{"title":"Targeting dendritic cells to drive PDAC immunotherapy response.","authors":"Alyssa G Weinstein, David G DeNardo","doi":"10.1016/j.tips.2024.10.009","DOIUrl":"10.1016/j.tips.2024.10.009","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma (PDAC) has been historically unresponsive to immunotherapy, predominantly due to lower antigen loads and a lack of tumor-infiltrating dendritic cells (DCs) and T cells. A recent study by Mahadevan and colleagues demonstrates that increasing DC infiltration through use of an engineered DC1 vaccine can sensitize PDAC to immunotherapy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1095-1096"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent advancements in vaccine research and development.
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-12-01 Epub Date: 2024-11-27 DOI: 10.1016/j.tips.2024.11.004
Jerry C Madukwe
{"title":"Recent advancements in vaccine research and development.","authors":"Jerry C Madukwe","doi":"10.1016/j.tips.2024.11.004","DOIUrl":"10.1016/j.tips.2024.11.004","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1083-1085"},"PeriodicalIF":13.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The 2024 New York City Integrative Structural Biology Symposium.
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-28 DOI: 10.1016/j.tips.2024.11.001
Pilar Cossio, Edward T Eng
{"title":"The 2024 New York City Integrative Structural Biology Symposium.","authors":"Pilar Cossio, Edward T Eng","doi":"10.1016/j.tips.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.tips.2024.11.001","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Allosteric antibodies: a novel paradigm in drug discovery. 异构抗体：药物发现的新范例。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-18 DOI: 10.1016/j.tips.2024.10.007
Léxane Fournier, Enrico Guarnera, Harald Kolmar, Stefan Becker
{"title":"Allosteric antibodies: a novel paradigm in drug discovery.","authors":"Léxane Fournier, Enrico Guarnera, Harald Kolmar, Stefan Becker","doi":"10.1016/j.tips.2024.10.007","DOIUrl":"https://doi.org/10.1016/j.tips.2024.10.007","url":null,"abstract":"<p><p>Allostery represents a fundamental mechanism in protein regulation, enabling modulation of protein function from sites distal to the active site. While traditionally explored in the context of small molecules, allosteric modulation is gaining traction as a main mode of action in the realm of antibodies, which offer enhanced specificity and reduced toxicity. This review delves into the rapidly growing field of allosteric antibodies, highlighting recent therapeutic advancements and novel druggability avenues. We also explore the potential of these antibodies as innovative tools in drug discovery and discuss contemporary strategies for designing novel allosteric antibodies, leveraging state-of-the-art computational approaches.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing CNS mitophagy: drug development and disease-relevant models. 增强中枢神经系统有丝分裂：药物开发和疾病相关模型。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI: 10.1016/j.tips.2024.09.002
Krishayant S Dhar, Brendan Townsend, Andrew P Montgomery, Jonathan J Danon, Julia K Pagan, Michael Kassiou
{"title":"Enhancing CNS mitophagy: drug development and disease-relevant models.","authors":"Krishayant S Dhar, Brendan Townsend, Andrew P Montgomery, Jonathan J Danon, Julia K Pagan, Michael Kassiou","doi":"10.1016/j.tips.2024.09.002","DOIUrl":"10.1016/j.tips.2024.09.002","url":null,"abstract":"<p><p>Mitophagy, the selective degradation of mitochondria, is impaired in many neurodegenerative diseases (NDs), resulting in an accumulation of dysfunctional mitochondria and neuronal damage. Although enhancing mitophagy shows promise as a therapeutic strategy, the clinical significance of mitophagy activators remains uncertain due to limited understanding and poor representation of mitophagy in the central nervous system (CNS). This review explores recent insights into which mitophagy pathways to target and the extent of modulation necessary to be therapeutic towards NDs. We also highlight the complexities of mitophagy in the CNS, highlighting the need for disease-relevant models. Last, we outline crucial aspects of in vitro models to consider during drug discovery, aiming to bridge the gap between preclinical research and clinical applications in treating NDs through mitophagy modulation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"982-996"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated computational approaches for advancing antimicrobial peptide development. 推进抗菌肽开发的综合计算方法。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-25 DOI: 10.1016/j.tips.2024.09.011
Yanpeng Fang, Yeshuo Ma, Kunqian Yu, Jie Dong, Wenbin Zeng
{"title":"Integrated computational approaches for advancing antimicrobial peptide development.","authors":"Yanpeng Fang, Yeshuo Ma, Kunqian Yu, Jie Dong, Wenbin Zeng","doi":"10.1016/j.tips.2024.09.011","DOIUrl":"10.1016/j.tips.2024.09.011","url":null,"abstract":"<p><p>The increasing prevalence of antimicrobial resistance has intensified the need for novel antimicrobial drugs. Antimicrobial peptides (AMPs) are promising alternative antibiotics due to their broad-spectrum activity and slower resistance development. However, the time-consuming, costly development and challenge of systematic optimization limit their translation into the clinic. Recently, integrating computational methods have led to breakthroughs in the precise design and optimization of AMPs, reduced resource consumption, and accelerated AMP development process. We highlight the application of these integrated approaches in AMP molecule discovery, optimization, and delivery and demonstrate the synergy of these strategies to fuel AMP development.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1046-1060"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neutrophil extracellular traps in wound healing. 伤口愈合过程中的中性粒细胞胞外捕获器
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI: 10.1016/j.tips.2024.09.007
Zhanyong Zhu, Shengzhi Zhou, Sicheng Li, Song Gong, Qi Zhang
{"title":"Neutrophil extracellular traps in wound healing.","authors":"Zhanyong Zhu, Shengzhi Zhou, Sicheng Li, Song Gong, Qi Zhang","doi":"10.1016/j.tips.2024.09.007","DOIUrl":"10.1016/j.tips.2024.09.007","url":null,"abstract":"<p><p>Wound healing is a complex and orchestrated process that involves hemostasis, inflammation, proliferation, and tissue remodeling. Neutrophil extracellular traps (NETs) are intricate web-like structures released by neutrophils, comprising decondensed chromatin, myeloperoxidase (MPO), and neutrophil elastase (NE), which play vital roles in regulating neutrophil-mediated immune regulation. While NETs contribute to wound healing, excessive activation induced by dysregulated inflammation can hinder the healing process. Understanding the pivotal role of NETs in wound healing and tissue remodeling, as well as their intricate interactions within the wound microenvironment, presents opportunities for innovative wound healing strategies. In this review we discuss the process of NET formation, explore the interactions between NETs and skin cells, and examine therapeutic strategies targeting NETs and drug delivery platforms to accelerate wound healing. Additionally, we discuss current clinical investigations and research challenges towards advancing wound care practices.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1033-1045"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Balancing immune activation with Itk. 用 Itk 平衡免疫激活。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-02 DOI: 10.1016/j.tips.2024.09.005
Zenia Kaul, Pamela L Schwartzberg
{"title":"Balancing immune activation with Itk.","authors":"Zenia Kaul, Pamela L Schwartzberg","doi":"10.1016/j.tips.2024.09.005","DOIUrl":"10.1016/j.tips.2024.09.005","url":null,"abstract":"<p><p>Development of protective immune responses relies on a balance between proinflammatory CD4 T helper (Th) cell populations such as Th17 cells and regulatory CD4 T cells (Tregs) that keep immune activation in check. Evidence that interleukin-2-inducible T cell kinase (Itk) regulates this balance supports therapeutic applications for Itk inhibition.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"958-960"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chemical proteomic mapping of reversible small molecule binding sites in native systems. 绘制原生系统中可逆小分子结合位点的化学蛋白质组图谱。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1016/j.tips.2024.09.001
Jacob M Wozniak, Weichao Li, Christopher G Parker
{"title":"Chemical proteomic mapping of reversible small molecule binding sites in native systems.","authors":"Jacob M Wozniak, Weichao Li, Christopher G Parker","doi":"10.1016/j.tips.2024.09.001","DOIUrl":"10.1016/j.tips.2024.09.001","url":null,"abstract":"<p><p>The impact of small molecules in human biology are manifold; not only are they critical regulators of physiological processes, but they also serve as probes to investigate biological pathways and leads for therapeutic development. Identifying the protein targets of small molecules, and where they bind, is critical to understanding their functional consequences and potential for pharmacological use. Over the past two decades, chemical proteomics has emerged as a go-to strategy for the comprehensive mapping of small molecule-protein interactions. Recent advancements in this field, particularly innovations of photoaffinity labeling (PAL)-based methods, have enabled the robust identification of small molecule binding sites on protein targets, often in live cells. In this opinion article, we examine these advancements as well as reflect on how their strategic integration with other emerging tools can advance therapeutic development.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"969-981"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Voltage-gated ion channels in epilepsies: circuit dysfunctions and treatments. 癫痫中的电压门控离子通道：回路功能障碍和治疗方法。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1016/j.tips.2024.09.004
Dominique Debanne, Konstantina Mylonaki, Maria Laura Musella, Michaël Russier
{"title":"Voltage-gated ion channels in epilepsies: circuit dysfunctions and treatments.","authors":"Dominique Debanne, Konstantina Mylonaki, Maria Laura Musella, Michaël Russier","doi":"10.1016/j.tips.2024.09.004","DOIUrl":"10.1016/j.tips.2024.09.004","url":null,"abstract":"<p><p>Epileptic encephalopathies are generally considered to be functional disruptions in the balance between neural excitation and inhibition. Excitatory and inhibitory voltage-gated ion channels are key targets of antiepileptic drugs, playing a critical role in regulating neuronal excitation and synaptic transmission. Recent research has highlighted the significance of ion channels in various aspects of epilepsy, including presynaptic neurotransmitter release, intrinsic neuronal excitability, and neural synchrony. Genetic alterations in excitatory and inhibitory ion channels within principal neurons and in inhibitory interneurons have also been identified as key contributors to the development of epilepsies. We review these recent studies and shed light on the bidirectional relationship between epilepsy and neuronal excitability and the latest advancements in pharmacological therapeutics targeting ion channels for epilepsy treatment.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1018-1032"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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