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Trends in pharmacological sciences最新文献

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Exploring neutrophils as therapeutic targets in cardiometabolic diseases. 探索中性粒细胞作为心脏代谢疾病的治疗靶点。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-02-01 Epub Date: 2025-01-23 DOI: 10.1016/j.tips.2024.12.003
Mattia Albiero, Andrea Baragetti
{"title":"Exploring neutrophils as therapeutic targets in cardiometabolic diseases.","authors":"Mattia Albiero, Andrea Baragetti","doi":"10.1016/j.tips.2024.12.003","DOIUrl":"10.1016/j.tips.2024.12.003","url":null,"abstract":"<p><p>Current therapies for diabetes and atherosclerotic cardiovascular diseases (ACVDs) mainly target metabolic risk factors, but often fall short in addressing systemic inflammation, a key driver of disease onset and progression. Advances in our understanding of the biology of neutrophils, the cells that are principally involved in inflammatory situations, have highlighted their pivotal role in cardiometabolic diseases. Yet, neutrophils can reprogram their immune-metabolic functions based on the energetic substrates available, thus influencing both tissue homeostasis and the resolution of inflammation. In this review, we examine the effects of canonical therapies for cardiometabolic diseases on the key molecular pathways through which neutrophils respond to inflammatory stimuli. In addition, we explore potential synergies between these established therapeutic approaches and the anti-inflammatory therapies being evaluated for repurposing in the treatment of cardiometabolic diseases.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"102-116"},"PeriodicalIF":13.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041964","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
Tension-induced organelle stress: an emerging target in fibrosis. 紧张诱导的细胞器应激：纤维化的新靶点。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-02-01 Epub Date: 2025-01-15 DOI: 10.1016/j.tips.2024.12.006
FuiBoon Kai, Andrew M Leidal, Valerie M Weaver
{"title":"Tension-induced organelle stress: an emerging target in fibrosis.","authors":"FuiBoon Kai, Andrew M Leidal, Valerie M Weaver","doi":"10.1016/j.tips.2024.12.006","DOIUrl":"10.1016/j.tips.2024.12.006","url":null,"abstract":"<p><p>Fibrosis accounts for approximately one-third of disease-related deaths globally. Current therapies fail to cure fibrosis, emphasizing the need to identify new antifibrotic approaches. Fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) and resultant stiffening of tissue stroma. This stiffening appropriates actomyosin-mediated mechanical tension within cells to ultimately affect cell fate decisions and function. Recent studies demonstrate that subcellular organelles are physically connected to the actin cytoskeleton and sensitive to mechanoperturbations. These insights highlight mechanisms that may contribute to the chronic organelle stress in many fibrotic diseases, including those of the lung and liver. In this review, we discuss the hypothesis that a stiffened fibrotic ECM corrupts intracellular mechanical tension to compromise organelle homeostasis. We summarize potential therapeutics that could intervene in this mechanical dialog and that may have clinical benefit for resolving pathological organelle stress in fibrosis.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"117-131"},"PeriodicalIF":13.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012268","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
Advances in the structural understanding of opioid allostery. 阿片变构的结构研究进展。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-02-01 Epub Date: 2025-01-17 DOI: 10.1016/j.tips.2024.12.007
Nokomis Ramos-Gonzalez, Balazs R Varga, Susruta Majumdar
{"title":"Advances in the structural understanding of opioid allostery.","authors":"Nokomis Ramos-Gonzalez, Balazs R Varga, Susruta Majumdar","doi":"10.1016/j.tips.2024.12.007","DOIUrl":"10.1016/j.tips.2024.12.007","url":null,"abstract":"<p><p>Activation of the μ opioid receptor (MOR) can give analgesia, but also has dangerous side effects. Drugs that target MOR through an allosteric site, meaning they bind outside of the usual pocket, present a novel mode of receptor activation with different pharmacology relative to orthosteric drugs. Recent structural studies give valuable new information on how allosteric modulators interact with MOR.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"98-101"},"PeriodicalIF":13.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012265","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
A novel pharmacological entity toward integrated multimodal immunotherapy. 一种面向综合多模式免疫治疗的新型药理实体。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-02-01 Epub Date: 2024-12-24 DOI: 10.1016/j.tips.2024.12.001
Rafael Sirera, Manuel Beltrán-Visiedo, Lorenzo Galluzzi
{"title":"A novel pharmacological entity toward integrated multimodal immunotherapy.","authors":"Rafael Sirera, Manuel Beltrán-Visiedo, Lorenzo Galluzzi","doi":"10.1016/j.tips.2024.12.001","DOIUrl":"10.1016/j.tips.2024.12.001","url":null,"abstract":"<p><p>Most solid tumors are insensitive to single-agent immunotherapy, calling for the development of combinatorial treatment regimens. Recently, Lin and collaborators developed a pharmacological platform enabling the combination of different immunotherapies into a single chemical entity. This approach may effectively circumvent obstacles associated with the simultaneous delivery of multiple immunotherapeutic agents.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"95-97"},"PeriodicalIF":13.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898417","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
Boosting CAR-T cell therapy through vaccine synergy. 通过疫苗协同促进CAR-T细胞治疗。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-02-01 Epub Date: 2025-01-03 DOI: 10.1016/j.tips.2024.12.004
Yan-Ruide Li, Zibai Lyu, Xinyuan Shen, Ying Fang, Lili Yang
{"title":"Boosting CAR-T cell therapy through vaccine synergy.","authors":"Yan-Ruide Li, Zibai Lyu, Xinyuan Shen, Ying Fang, Lili Yang","doi":"10.1016/j.tips.2024.12.004","DOIUrl":"10.1016/j.tips.2024.12.004","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematological cancers. However, achieving comparable success in solid tumors remains challenging. Factors contributing to these limitations include the scarcity of tumor-specific antigens (TSAs), insufficient CAR-T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Vaccine-based strategies are emerging as potential approaches to address these challenges, enhancing CAR-T cell expansion, persistence, and antitumor efficacy. In this review, we explore diverse vaccine modalities, including mRNA, peptide, viral vector, and dendritic cell (DC)-based vaccines, and their roles in augmenting CAR-T cell responses. Special focus is given to recent clinical advancements combining mRNA-based vaccines with CAR-T therapy for the treatment of genitourinary cancers. In addition, we discuss crucial considerations for optimizing vaccine dosing, scheduling, and delivery to maximize CAR-T synergy, aiming to refine this combination strategy to improve treatment efficacy and safety.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"180-199"},"PeriodicalIF":13.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928350","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
Data and AI-driven synthetic binding protein discovery. 数据和人工智能驱动的合成结合蛋白发现。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-02-01 Epub Date: 2025-01-03 DOI: 10.1016/j.tips.2024.12.002
Yanlin Li, Zixin Duan, Zhenwen Li, Weiwei Xue
{"title":"Data and AI-driven synthetic binding protein discovery.","authors":"Yanlin Li, Zixin Duan, Zhenwen Li, Weiwei Xue","doi":"10.1016/j.tips.2024.12.002","DOIUrl":"10.1016/j.tips.2024.12.002","url":null,"abstract":"<p><p>Synthetic binding proteins (SBPs) are a class of protein binders that are artificially created and do not exist naturally. Their broad applications in tackling challenges of research, diagnostics, and therapeutics have garnered significant interest. Traditional protein engineering is pivotal to the discovery of SBPs. Recently, this discovery has been significantly accelerated by computational approaches, such as molecular modeling and artificial intelligence (AI). Furthermore, while numerous bioinformatics databases offer a wealth of resources that fuel SBP discovery, the full potential of these data has not yet been fully exploited. In this review, we present a comprehensive overview of SBP data ecosystem and methodologies in SBP discovery, highlighting the critical role of high-quality data and AI technologies in accelerating the discovery of innovative SBPs with promising applications in pharmacological sciences.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"132-144"},"PeriodicalIF":13.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928460","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
Therapeutic potential of cannabidiol polypharmacology in neuropsychiatric disorders. 大麻二酚多药理学在神经精神疾病中的治疗潜力。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-02-01 Epub Date: 2025-01-20 DOI: 10.1016/j.tips.2024.12.005
Olivier J Manzoni, Antonia Manduca, Viviana Trezza
{"title":"Therapeutic potential of cannabidiol polypharmacology in neuropsychiatric disorders.","authors":"Olivier J Manzoni, Antonia Manduca, Viviana Trezza","doi":"10.1016/j.tips.2024.12.005","DOIUrl":"10.1016/j.tips.2024.12.005","url":null,"abstract":"<p><p>Cannabidiol (CBD), the primary non-intoxicating compound in cannabis, is currently approved for treating rare, treatment-resistant seizures. Recent preclinical research suggests that CBD's multifaceted mechanisms of action in the brain, which involve multiple molecular targets, underlie its neuroprotective, anti-inflammatory, anxiolytic, and antipsychotic effects. Clinical trials are also exploring CBD's therapeutic potential beyond its current uses. This review focuses on CBD's polypharmacological profile and discusses the latest preclinical and clinical findings regarding its efficacy in neuropsychiatric disorders. Existing evidence suggests that CBD's ability to modulate multiple signaling pathways may benefit neuropsychiatric disorders, and we propose further research areas to clarify its mechanisms, address data gaps, and refine its therapeutic indications.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"145-162"},"PeriodicalIF":13.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012269","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
Model-informed precision dosing in inflammatory bowel diseases. 炎症性肠病的模型信息精确给药。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-01-01 Epub Date: 2024-12-03 DOI: 10.1016/j.tips.2024.11.003
Arno R Bourgonje, Marla C Dubinsky, Ron J Keizer, Erwin Dreesen, Paola Mian
{"title":"Model-informed precision dosing in inflammatory bowel diseases.","authors":"Arno R Bourgonje, Marla C Dubinsky, Ron J Keizer, Erwin Dreesen, Paola Mian","doi":"10.1016/j.tips.2024.11.003","DOIUrl":"10.1016/j.tips.2024.11.003","url":null,"abstract":"<p><p>Therapeutic drug monitoring (TDM) for biologic therapies in inflammatory bowel disease (IBD) primarily aims to optimize dosing. However, several unmet needs remain. These include the identification of optimal drug concentrations, accounting for variability in pharmacokinetics (PK) and pharmacodynamics (PD), and the frequent delays between sampling and clinical decision-making. Recent technical advances, such as population PK/PD modeling and model-informed precision dosing (MIPD) tools developed from such models, as well as point-of-care (POC) and self-sampling assays and novel software programs, offer potential solutions. Successful implementation of these innovations may help to establish MIPD for patients with IBD. This would enable personalized dosing, advancing a one-size-fits-all approach to TDM that currently is inadequate to fulfill the needs for every patient with IBD.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"9-19"},"PeriodicalIF":13.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780911","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. 2024年纽约市综合结构生物学研讨会。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-01-01 Epub Date: 2024-11-29 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":"10.1016/j.tips.2024.11.001","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1-8"},"PeriodicalIF":13.9,"publicationDate":"2025-01-01","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
Demographic diversity in platelet function and response to antiplatelet therapy. 血小板功能的人口多样性及其对抗血小板治疗的反应。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-01-01 Epub Date: 2024-12-12 DOI: 10.1016/j.tips.2024.11.005
Kanika Jain, Tarun Tyagi, Sean X Gu, E Vincent S Faustino, John Hwa
{"title":"Demographic diversity in platelet function and response to antiplatelet therapy.","authors":"Kanika Jain, Tarun Tyagi, Sean X Gu, E Vincent S Faustino, John Hwa","doi":"10.1016/j.tips.2024.11.005","DOIUrl":"10.1016/j.tips.2024.11.005","url":null,"abstract":"<p><p>Recent studies have highlighted the complexity of platelet biology, revealing their diverse roles beyond hemostasis. Pathological platelet activation is now recognized as a key contributor to thrombosis and inflammation that are both central to cardiovascular disease (CVD). Emerging research emphasizes the significant impact of demographic factors - such as age, sex, race, and ethnicity - on CVD risk and responses to antiplatelet therapies. These population-based differences, shaped by genetic and non-genetic factors, highlight the need for reevaluation of antiplatelet strategies. We address current knowledge and emphasize the pressing need for further research into platelet biology and cardiovascular outcomes across diverse populations. In this review we advocate for tailored therapeutic approaches in CVD based on the recent demographic-focused findings.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"78-93"},"PeriodicalIF":13.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11710996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822706","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
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