Pharmacology & Therapeutics最新文献

Unveiling the silent threat: COVID-19 and myocardial injury 揭示无声的威胁：COVID-19和心肌损伤。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-06-27 DOI: 10.1016/j.pharmthera.2025.108904

Ke Xu , Wu He , Bo Yu, James Jiqi Wang, Junfang Wu, Dao Wen Wang

{"title":"Unveiling the silent threat: COVID-19 and myocardial injury","authors":"Ke Xu , Wu He , Bo Yu, James Jiqi Wang, Junfang Wu, Dao Wen Wang","doi":"10.1016/j.pharmthera.2025.108904","DOIUrl":"10.1016/j.pharmthera.2025.108904","url":null,"abstract":"<div><div>Since COVID-19 firstly appeared in 2019 December, it has been defined as an infectious disease mainly performing lung symptoms, which contracted more attention. However, more and more findings indicate myocardial injury appears in considerable proportion of COVID-19 patients (30 % – 50 %) not only but also major cause leading to the death in patients, many of whom may be even without severe respiratory symptoms. Meanwhile myocarditis after injecting vaccines has been paid more attention to globally which always performs uncontrollable inflammation and lead to death. Now myocardial injury has been a main complication in patients with long COVID-19, which is worthy of attention. Furthermore, myocardial injury or myocarditis is detectable and treatable. In order to abstract attention to myocardial injury associated with COVID-19 and provide more evidence and experience for patients who still suffer myocardial injury from COVID-19 vaccines or long COVID-19, the review comprehensively summarized previous researches from pathogenesis, clinical symptoms, diagnosis and treatment and emphasized the crucial role of RASS inhibitors especially ARBs.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"273 ","pages":"Article 108904"},"PeriodicalIF":12.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525844","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

Antiviral drug repurposing: different approaches and the case of antifungal drugs 抗病毒药物的再利用：不同的方法和抗真菌药物的案例。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-06-23 DOI: 10.1016/j.pharmthera.2025.108903

Sara Tuci , Beatrice Mercorelli , Arianna Loregian

{"title":"Antiviral drug repurposing: different approaches and the case of antifungal drugs","authors":"Sara Tuci , Beatrice Mercorelli , Arianna Loregian","doi":"10.1016/j.pharmthera.2025.108903","DOIUrl":"10.1016/j.pharmthera.2025.108903","url":null,"abstract":"<div><div>In recent years, the emergence of new viruses and the re-emergence of old ones have posed a significant challenge to global Public Health. Viruses characterised by high morbidity and mortality rates have the potential to spread rapidly, causing large epidemic outbreaks and even pandemics. In this context, viral infections still lacking effective treatments represent a serious threat to human health. For this reason, sustained development and implementation of countermeasures are urgently needed against these infections, as they are for diseases for which the emergence of drug resistance is rapidly increasing. In this regard, compared to <em>de novo</em> drug discovery, drug repurposing could represent a highly efficient, faster, and more affordable strategy to develop new drugs. Here, we provide a comprehensive review of the different experimental and computational approaches used for drug repurposing and discuss their advantages and limitations in comparison with other drug discovery strategies. In addition, as an example of the successful application of drug repurposing, we present the case of approved antifungal drugs that could be repurposed to counteract viral infections.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"273 ","pages":"Article 108903"},"PeriodicalIF":12.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493302","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

Retinoid dynamics in vision: from visual cycle biology to retina disease treatments 视觉中的类维甲酸动力学：从视觉周期生物学到视网膜疾病治疗。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-06-21 DOI: 10.1016/j.pharmthera.2025.108902

Jaclyn Swigris , Made Airanthi K. Widjaja-Adhi , Marcin Golczak

{"title":"Retinoid dynamics in vision: from visual cycle biology to retina disease treatments","authors":"Jaclyn Swigris , Made Airanthi K. Widjaja-Adhi , Marcin Golczak","doi":"10.1016/j.pharmthera.2025.108902","DOIUrl":"10.1016/j.pharmthera.2025.108902","url":null,"abstract":"<div><div>Light perception is a biological process that facilitates a profound interaction between the external world and the internal functions of living organisms. It begins with the absorption of photons with specialized visual pigments that contain vitamin A-derived chromophores. The light energy triggers the photoisomerization of the visual chromophore, initiating a cascade of signaling events that ultimately convert light into electrical signals interpreted as vision. However, the sustainability of vision relies on the continuous supply of the visual chromophore, which is maintained through light-dependent and light-independent processes. The importance of these processes is underscored by numerous blinding retinal diseases linked to impaired regeneration of the chromophore. Thus, research into the molecular mechanisms of visual chromophore biosynthesis has not only deepened our understanding of the organization of visual systems but also uncovered the etiologies of these debilitating diseases. In this review, we synthesize recent progress in understanding the mechanisms responsible for visual chromophore biosynthesis. We examine biological targets, therapeutic strategies, and drug discovery efforts aimed at restoring or bypassing metabolic blockades in visual chromophore regeneration, and assess the progress of clinical trials evaluating the effectiveness of therapies for degenerative retinal diseases.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"273 ","pages":"Article 108902"},"PeriodicalIF":12.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473625","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

Targeting myeloid cell immunometabolism to improve current non-small cell lung cancer therapies 靶向骨髓细胞免疫代谢改善当前非小细胞肺癌治疗。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-06-04 DOI: 10.1016/j.pharmthera.2025.108893

Marah C. Runtsch , Stefano Angiari , Julia Kargl

{"title":"Targeting myeloid cell immunometabolism to improve current non-small cell lung cancer therapies","authors":"Marah C. Runtsch , Stefano Angiari , Julia Kargl","doi":"10.1016/j.pharmthera.2025.108893","DOIUrl":"10.1016/j.pharmthera.2025.108893","url":null,"abstract":"<div><div>Although recent advancements in immunotherapy have improved clinical outcomes, non-small cell lung cancer (NSCLC) is still the deadliest cancer type, as current treatments fail in many patients. This highlights a need for continued studies on this complex and multifaceted malignancy. The lung tumor microenvironment (TME) is marked by an infiltration of innate immune cells of the myeloid lineage, including macrophages and neutrophils, which affect patient outcomes. These cells induce inflammation and functional responses that can both promote and inhibit tumor growth and progression, with these functions being directly linked to their intracellular metabolism. The lung TME provides a milieu of signals, including cytokines and metabolites, that induce metabolic reprogramming in tumor-associated myeloid cells. Here, we review the present understanding of tumor-associated myeloid cell metabolism specifically in the context of NSCLC. Recent studies demonstrated that some metabolic pathways have the potential to be manipulated pharmacologically to eliminate or reprogram pathogenic, pro-tumor, and/or immunosuppressive myeloid cells to anti-tumor states for NSCLC therapies. Therefore, we highlight and propose potential metabolic targets in these myeloid cells, focusing on macrophages and neutrophils. These cells have direct roles in affecting subsequent responses of adaptive cells and their cellular metabolism must be further investigated to identify potential pharmacologic therapeutic targets. Targeting myeloid cell metabolism in the TME may be used in combination with the current regimen of immune checkpoint inhibition (ICI) and chemotherapy to improve outcomes for lung cancer patients.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"273 ","pages":"Article 108893"},"PeriodicalIF":12.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245526","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

Current and future therapeutics targeting mast cells in disease 目前和未来针对肥大细胞的疾病治疗方法。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-05-30 DOI: 10.1016/j.pharmthera.2025.108892

William P.M. Worrall, Laurent L. Reber

引用次数: 0

Corrigendum to “Immunomodulation and targeted drug delivery with high intensity focused ultrasound (HIFU): Principles and mechanisms” [Volume 244, April 2023, 108393] “高强度聚焦超声（HIFU）的免疫调节和靶向药物递送：原理和机制”的勘误表[第244卷，2023年4月，108393]

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-05-30 DOI: 10.1016/j.pharmthera.2025.108890

Harshini Ashar, Happy Agarwal, Ashish Ranjan

引用次数: 0

Post-COVID pulmonary sequelae: Mechanisms and potential targets to reduce persistent fibrosis covid后肺后遗症：减少持续性纤维化的机制和潜在靶点

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-05-28 DOI: 10.1016/j.pharmthera.2025.108891

Emma C.A. Vreeman , Janesh Pillay , Janette K. Burgess

{"title":"Post-COVID pulmonary sequelae: Mechanisms and potential targets to reduce persistent fibrosis","authors":"Emma C.A. Vreeman , Janesh Pillay , Janette K. Burgess","doi":"10.1016/j.pharmthera.2025.108891","DOIUrl":"10.1016/j.pharmthera.2025.108891","url":null,"abstract":"<div><div>After the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) pandemic, the emergence of long-term sequelae post-infection poses a new healthcare challenge. Following initial infection with SARS-CoV-2, approximately 1 in 10 people experience post-acute sequelae of COVID-19 (PASC), also known as long COVID. PASC can affect the entire body, with the airways and lungs being a primary target of the initial viral infection. Many post-COVID symptoms have been associated with fibrotic lung lesions and diminished respiratory function. The reversibility, persistence, or progression of post-COVID-19 pulmonary fibrosis is still a topic of debate. We aimed to compare current findings and examined similar viral infections from the past, to increase understanding of prevalence, persistence and possible pharmacological targets of post-COVID-19 pulmonary fibrosis.</div><div>Recent studies have documented PASC symptoms persisting up to 3 years post-recovery, and lung impairments present after 15 years after infection with the similar SARS-CoV virus in 2003. These findings suggest the potential for long-term pulmonary fibrosis following SARS-CoV-2 infection, highlighting the need for new anti-fibrotic treatments capable of reversing pulmonary fibrosis. Besides the approved anti-fibrotics, pirfenidone and nintedanib, other promising treatments include histone deacetylase inhibitors, angiotensin receptor blockers and mesenchymal stem cells. The pathophysiological mechanisms underlying post-COVID-19 pulmonary fibrosis are still incompletely understood, necessitating future research to clarify the development of persistent post-COVID-19 pulmonary fibrosis following SARS-CoV-2 infection. Given the widespread transmission of SARS-CoV-2, even a low prevalence of persistent post-COVID-19 pulmonary fibrosis would represent a significant public health concern for which therapeutic strategies are essential to identify.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"272 ","pages":"Article 108891"},"PeriodicalIF":12.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186159","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 advances in therapeutic targeting of the KRAS pathway in cancer KRAS通路靶向治疗肿瘤的研究进展。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-05-28 DOI: 10.1016/j.pharmthera.2025.108889

Nadia Hitchen , Sarah Williams , Jayesh Desai

{"title":"Recent advances in therapeutic targeting of the KRAS pathway in cancer","authors":"Nadia Hitchen , Sarah Williams , Jayesh Desai","doi":"10.1016/j.pharmthera.2025.108889","DOIUrl":"10.1016/j.pharmthera.2025.108889","url":null,"abstract":"<div><div>Recent advances in cancer therapy have significantly progressed through targeted inhibition of the rat sarcoma virus (RAS) signalling pathway, particularly focusing on Kirsten rat sarcoma virus (KRAS) mutations prevalent in cancers such as non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). Historically deemed “undruggable,” KRAS mutations, especially KRASG12C and KRASG12D, are now effectively targeted by specific inhibitors that have demonstrated promising clinical results. Agents such as Sotorasib, Adagrasib, and Divarasib exhibit notable efficacy against KRASG12C mutations, particularly in NSCLC, with combination strategies significantly improving outcomes, especially in CRC. With over 50 agents currently in development, targeting KRAS has become a rapidly expanding area of cancer therapeutics. However, substantial challenges remain, including optimizing clinical trial designs, particularly in early-phase trials, and integrating pharmacodynamic tools to refine dosing and treatment schedules, thus achieving an optimal balance between efficacy and patient tolerability. This review summarizes recent therapeutic advancements, highlighting the clinical development of KRAS-specific inhibitors, and emphasizes future strategies involving a combination of mutant-specific and broader mutant-independent approaches to overcome resistance, thereby offering promise for more durable cancer control and expanded patient eligibility.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"273 ","pages":"Article 108889"},"PeriodicalIF":12.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186160","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

Alternative splicing in aging and aging-related diseases: From pathogenesis to therapy 衰老和衰老相关疾病的选择性剪接：从发病机制到治疗。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-05-23 DOI: 10.1016/j.pharmthera.2025.108887

Mingrui Han , Peiru Han , Zihui Wang , Lingdong Kong , Qiang Xu , Qianqian Liu , Yang Sun

引用次数: 0

N-methyl-D-aspartate receptors (NMDARs): a glutamate-activated cation channel with biased signaling and therapeutic potential in brain disorders n -甲基-d-天冬氨酸受体（NMDARs）：一种谷氨酸激活的阳离子通道，具有偏倚信号传导和治疗脑疾病的潜力。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-05-22 DOI: 10.1016/j.pharmthera.2025.108888

Xuan Zhang , Wensheng Cai , Chao Wang , Jing Tian

{"title":"N-methyl-D-aspartate receptors (NMDARs): a glutamate-activated cation channel with biased signaling and therapeutic potential in brain disorders","authors":"Xuan Zhang , Wensheng Cai , Chao Wang , Jing Tian","doi":"10.1016/j.pharmthera.2025.108888","DOIUrl":"10.1016/j.pharmthera.2025.108888","url":null,"abstract":"<div><div>N-methyl-D-aspartate receptors (NMDARs) are a class of calcium-permeable ion channel that are extensively distributed throughout the body, composed of various subunits. The presence of diverse ligands and subcellular localizations of the receptors confers biased signaling and distinct functional roles. Activation of the NMDARs induces calcium influx, which plays a pivotal role in neurotransmitter release, synaptic plasticity, and intracellular signaling. Differential localization of NMDARs at synaptic and extrasynaptic sites results in divergent physiological effects; excessive or insufficient activation of NMDARs disrupts calcium homeostasis, leading to neuronal damage and subsequent neurological dysfunction as well as related diseases. Therefore, it is crucial to develop drugs targeting NMDARs with high efficacy and low toxicity for treating brain disorders associated with NMDARs abnormalities. In this review, we summarize both mechanism research and clinical studies on NMDARs while discussing potential therapeutic targets aimed at modulating ion channel activity through regulating mechanisms, subunit rearrangement, membrane expression, and the specific targeting of synaptic versus extrasynaptic NMDARs. Our aim is to provide new insights for innovative drug development.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"273 ","pages":"Article 108888"},"PeriodicalIF":12.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140959","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