Pharmacology & Therapeutics最新文献

{"title":"Neuromuscular and cardiac organoids and assembloids: Advanced platforms for drug testing","authors":"Lorenzo Fontanelli ,&nbsp;Noemi Nisini ,&nbsp;Sergio Pirola ,&nbsp;Fabio A. Recchia","doi":"10.1016/j.pharmthera.2025.108876","DOIUrl":"10.1016/j.pharmthera.2025.108876","url":null,"abstract":"<div><div>The inherent technical difficulties, ethical/regulatory issues and costs of experimental studies in animal models is prompting investigators to replace as much as possible living organisms with <em>in vitro</em> physiological models named organoids and assembloids. Generated from induced pluripotent stem cells, these three-dimensional structures approximate the complexity of tissues and their interactions, enabling personalized disease modelling and drug testing. The integration of multiple components in assembloids further enhances their predictive value for multi-system interactions and toxicities. This review describes how neuromuscular organoids, incorporating functional neuromuscular junctions and contractile muscle tissue, have been used to replicate, <em>in vitro</em>, complex neuromuscular morpho-functional structures, offering very valuable platforms to study molecular mechanisms and drug effects in models of incurable diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis. In the cardiological field, cardiac organoids and assembloids are proving reliable models for testing drug effects at molecular, morphological, electrophysiological and mechanical level. Recently, the integration of neuronal components into cardiac organoids has provided a potential approach to investigate autonomic function, a fundamental aspect of many neurological, neuromuscular and cardiac diseases. Challenges and limitations still remain, including the non-uniform differentiation protocols across studies, the incomplete maturation of cell phenotypes, and the lack of integrated pharmacokinetic modelling. We discussed some future developments aimed at overcoming such hurdles. Despite their current limitations, organoids and assembloids clearly hold great promises and will help advancing many fields of biomedicine.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"272 ","pages":"Article 108876"},"PeriodicalIF":12.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085592","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}

{"title":"Management of drug-resistant hypertension as a heterogeneous disorder","authors":"Reza Tabrizchi","doi":"10.1016/j.pharmthera.2025.108875","DOIUrl":"10.1016/j.pharmthera.2025.108875","url":null,"abstract":"<div><div>Approximately 1.3 billion adults globally have hypertension, and are at higher risk of death associated with cardiovascular disease. Adjusted death rate primarily due to high blood pressure is 31.3 per 100,000. The prevalence of drug-resistant hypertension is estimated to be up to 20 % in hypertensive individuals, and is more common in those with chronic kidney disease and obstructive sleep apnea. It occurs in individuals on ≥3 antihypertensive drugs including a diuretic. The addition of spironolactone, as a fourth drug has been found at times to be effective in management of blood pressure. Other strategies include sequential nephron block (e.g., spironolactone + furosemide + amiloride), and use of drugs such as alpha₂ agonists, endothelin antagonists, and nonsteroidal mineralocorticoid antagonists. Use of positive airway pressure and pharmacotherapy have been found to be of value in individuals with sleep apnea in lowering blood pressure. In contrast, baroreceptor stimulation and/or renal denervation combined with pharmacotherapy seem to offer little in a way of consistent efficacy of optimally lowering blood pressures. Remarkably, evidence in the literature strongly supports the view that life style changes including regular exercise and appropriate diet combined with pharmacotherapy can lead to positive outcomes in helping to significantly reduce blood pressure. There is also ample data in literature suggesting the non-compliance to antihypertensive medications as a significant barrier to lowering blood pressure in this group. Accordingly, education regarding pharmacotherapy, and appropriate exercise regimen, including changes to diet should underpin any strategy in the management of high blood pressure in this population.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"271 ","pages":"Article 108875"},"PeriodicalIF":12.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935759","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}

{"title":"Unlocking the power of affibody conjugated radioactive metallopharmaceuticals for targeted cancer diagnosis and therapy","authors":"Dhanashree Murugan ,&nbsp;Harashkumar Vasanthakumari Thirumalaiswamy ,&nbsp;Vasanth Murugesan ,&nbsp;Janarthanan Venkatesan ,&nbsp;Unnikrishnan Balachandran ,&nbsp;Kalaiarasu Lakshminarayanan ,&nbsp;Drishty Satpati ,&nbsp;Stefan Nikolić ,&nbsp;Loganathan Rangasamy","doi":"10.1016/j.pharmthera.2025.108863","DOIUrl":"10.1016/j.pharmthera.2025.108863","url":null,"abstract":"<div><div>Cancer is the second-largest death-causing disease after cardiovascular diseases. Effective research on cancer diagnosis and subsequent elimination plays a vital role in reducing the cancer-related death toll. Radiotherapy is one of the best strategies that could kill masses of solid tumour tissues; however, the efficacy is limited due to the bystander effect. This issue could be solved by the emergence of targeted delivery of radiometallic complexes, enabling clinicians to monitor the tumour regions and effectively destroy the tumour. Affibody® molecules are a class of synthetic peptides known as antibody mimics having the binding sites of an antibody. The specificity of affibodies is found to be greater than that of antibodies due to their small size. This review intends to highlight the recent developments in the field of affibody-targeted radiometallopharmaceuticals. These approaches could be essential for early cancer detection, tumour staging, and monitoring the response to therapy and could produce better therapeutic outcomes. In an attempt to provide ideas and inspiration for the researchers to design affibody-conjugated radiopharmaceuticals that are clinically applicable, we have provided an in-depth exploration of the various types of affibody-conjugated radiopharmaceuticals that are currently in clinical trials and various other pre-clinically tested conjugates in this article. Only a few review reports on affibody-conjugated radiometallopharmaceuticals, typically focusing on a specific molecular target or radionuclides reported. In this review, we provide a comprehensive overview of most radiometals, such as ¹¹¹In, ⁶⁸Ga, ⁶⁴Cu, ⁵⁵Co, ⁵⁷Co, ⁴⁴Sc, ^99mTc, ⁸⁹Zr, ⁹⁰Y, ²¹¹At, ¹⁸⁸Re, and ¹⁷⁷Lu, choice of chelators, and potential cancer-associated molecular targets such HER2, EGFR or HER1, HER3, IGF-1R, PDGFRβ, VEGFR2, PD-L1, CAIX, PD-L1, neonatal Fc receptor (FcRn) and B7-H3. This approach highlights the advancements made over the past twenty years in affibody conjugates for radio imaging and therapy in oncology.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"272 ","pages":"Article 108863"},"PeriodicalIF":12.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954530","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}

{"title":"USP1 inhibition: A journey from target discovery to clinical translation","authors":"Carlos Torrado ,&nbsp;Nicholas W. Ashton ,&nbsp;Alan D. D'Andrea ,&nbsp;Timothy A. Yap","doi":"10.1016/j.pharmthera.2025.108865","DOIUrl":"10.1016/j.pharmthera.2025.108865","url":null,"abstract":"<div><div>Ubiquitin-specific protease 1 (USP1) is a deubiquitinating enzyme involved in the DNA damage response. Upon DNA damage, USP1 stabilizes replication forks by removing monoubiquitin from PCNA and FANCD2-FANCI, thereby catalyzing critical final steps in translesion synthesis and interstrand crosslink (ICL) repair. This function is particularly crucial in <em>BRCA1</em> mutant cancers, where the homologous recombination pathway is compromised, leading tumors to rely on USP1 for effective repair. USP1 is also overexpressed in <em>BRCA1</em> mutant cancers, as well as other tumor types. Preclinical studies have demonstrated that knockout of USP1 is synthetically lethal in tumors with biallelic BRCA1 mutations, and this relationship is enhanced by combination with PARP inhibitors. Newly developed USP1 inhibitors have confirmed this synthetic lethality in BRCA1-deficient tumor cells. Moreover, these drugs have the potential for resensitizing platinum-resistant tumors. Currently, potent and specific USP1 inhibitors are undergoing evaluation in phase I clinical trials. RO7623066 (KSQ-4279) reported an acceptable safety profile during a phase I dose escalation study, with anemia being the most common side effect, and demonstrated robust pharmacokinetic, pharmacodynamic, and clinical activity. Other USP1 inhibitors, including SIM0501, XL309–101, and HSK39775, are currently in early clinical development. In this review, we provide an overview of the molecular function of USP1 and its importance as a therapeutic target in oncology, before focusing on the current state of preclinical and clinical development of USP1 inhibitors.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"271 ","pages":"Article 108865"},"PeriodicalIF":12.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873285","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}

{"title":"Therapeutic potential of natural flavonoids in atherosclerosis through endothelium-protective mechanisms: An update","authors":"Chao Zhong ,&nbsp;Keke Deng ,&nbsp;Xiaoya Lang ,&nbsp;Dan Shan ,&nbsp;Yanfei Xie ,&nbsp;Wen Pan ,&nbsp;Jun Yu","doi":"10.1016/j.pharmthera.2025.108864","DOIUrl":"10.1016/j.pharmthera.2025.108864","url":null,"abstract":"<div><div>Atherosclerosis and its associated cardiovascular complications remain significant global public health challenges, underscoring the urgent need for effective therapeutic strategies. Endothelial cells are critical for maintaining vascular health and homeostasis, and their dysfunction is a key contributor to the initiation and progression of atherosclerosis. Targeting endothelial dysfunction has, therefore, emerged as a promising approach for the prevention and management of atherosclerosis. Among natural products, flavonoids, a diverse class of plant-derived phenolic compounds, have garnered significant attention for their anti-atherosclerotic properties. A growing body of evidence demonstrates that flavonoids can mitigate endothelial dysfunction, highlighting their potential as endothelial dysfunction-targeted therapeutics for atherosclerosis. In this review, we summarize current knowledge on the roles of natural flavonoids in modulating various aspects of endothelial dysfunction and their therapeutic effects on atherosclerosis, focusing on the underlying molecular mechanisms. We also discuss the challenges and future prospects of translating natural flavonoids into clinical applications for cardiovascular medicine. This review aims to provide critical insights to advance the development of novel endothelium-protective pharmacotherapies for atherosclerosis.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"271 ","pages":"Article 108864"},"PeriodicalIF":12.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879029","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}

{"title":"Retina-directed gene therapy: Achievements and remaining challenges","authors":"Josef Biber ,&nbsp;Catharina Gandor ,&nbsp;Elvir Becirovic ,&nbsp;Stylianos Michalakis","doi":"10.1016/j.pharmthera.2025.108862","DOIUrl":"10.1016/j.pharmthera.2025.108862","url":null,"abstract":"<div><div>Gene therapy is an innovative medical approach that offers new treatment options for congenital and acquired diseases by transferring, correcting, inactivating or regulating genes to supplement, replace or modify a gene function. The approval of voretigene neparvovec (Luxturna), a gene therapy for <em>RPE65</em>-associated retinopathy, has marked a milestone for the field of retinal gene therapy, but has also helped to accelerate the development of gene therapies for genetic diseases affecting other organs. Voretigene neparvovec is a vector based on adeno-associated virus (AAV) that delivers a functional copy of <em>RPE65</em> to supplement the missing function of this gene. The AAV-based gene delivery has proven to be versatile and safe for the transfer of genetic material to retinal cells. However, challenges remain in treating additional inherited as well as acquired retinopathies with this technology. Despite the high level of activity in this field, no other AAV gene therapy for retinal diseases has been approved since voretigene neparvovec. Ongoing research focuses on overcoming the current restraints through innovative strategies like AAV capsid engineering, dual-AAV vector systems, or CRISPR/Cas-mediated genome editing. Additionally, AAV gene therapy is being explored for the treatment of complex acquired diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) by targeting molecules involved in the pathobiology of the degenerative processes. This review outlines the current state of retinal gene therapy, highlighting ongoing challenges and future directions.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"271 ","pages":"Article 108862"},"PeriodicalIF":12.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899597","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}

{"title":"Characteristics and pharmacological responsiveness in hiPSC models of inherited cardiomyopathy","authors":"Merel Gerritse ,&nbsp;Willem B. van Ham ,&nbsp;Chris Denning ,&nbsp;Toon A.B. van Veen ,&nbsp;Renee G.C. Maas","doi":"10.1016/j.pharmthera.2025.108845","DOIUrl":"10.1016/j.pharmthera.2025.108845","url":null,"abstract":"<div><div>Inherited cardiomyopathies are a major cause of heart failure in all age groups, often with an onset in adolescence or early adult life. More than a thousand variants in approximately one hundred genes are associated with cardiomyopathies. Interestingly, many genetic cardiomyopathies display overlapping phenotypical defects in patients, despite the diversity of the initial pathogenic variants. Understanding how the underlying pathophysiology of genetic cardiomyopathies leads to these phenotypes will improve insights into a patient's disease course, and creates the opportunity for conceiving treatment strategies. Moreover, therapeutic strategies can be used to treat multiple cardiomyopathies based on shared phenotypes. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer reliable, high-throughput models for studying molecular and cellular characteristics of hereditary cardiomyopathies. hiPSC-CMs are produced relatively easily, either by directly originating them from patients, or by introducing patient-specific genetic variants in healthy lines. This review evaluates 90 studies on 24 cardiomyopathy-associated genes and systematically summarises the morphological and functional phenotypes observed in hiPSC-CMs. Additionally, treatment strategies applied in cardiomyopathic hiPSC-CMs are compiled and scored for effectiveness. Multiple overlapping phenotypic defects were identified in cardiomyocytes with different variants, whereas certain characteristics were only associated with specific genetic variants. Based on these findings, common mechanisms, therapeutic prospects, and considerations for future research are discussed with the aim to improve clinical translation from hiPSC-CMs to patients.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"272 ","pages":"Article 108845"},"PeriodicalIF":12.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951711","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}

{"title":"Cardiovascular therapeutic targets of sodium-glucose co-transporter 2 (SGLT2) inhibitors beyond heart failure","authors":"Matteo Armillotta ,&nbsp;Francesco Angeli ,&nbsp;Pasquale Paolisso ,&nbsp;Marta Belmonte ,&nbsp;Emanuel Raschi ,&nbsp;Guido Di Dalmazi ,&nbsp;Sara Amicone ,&nbsp;Lisa Canton ,&nbsp;Damiano Fedele ,&nbsp;Nicole Suma ,&nbsp;Alberto Foà ,&nbsp;Luca Bergamaschi ,&nbsp;Carmine Pizzi","doi":"10.1016/j.pharmthera.2025.108861","DOIUrl":"10.1016/j.pharmthera.2025.108861","url":null,"abstract":"<div><div>Sodium-glucose co-transporter 2 (SGLT2) inhibitors are oral antidiabetic agents that have shown significant improvements in cardiovascular and renal outcomes among patients with heart failure (HF), regardless of diabetic status, establishing them as a cornerstone therapy.</div><div>In addition to glycemic control and the osmotic diuretic effect, the inhibition of SGLT2 improves endothelial function and vasodilation, optimizing myocardial energy metabolism and preserving cardiac contractility. Moreover, SGLT2 inhibitors may exhibit anti-inflammatory properties and attenuate acute myocardial ischemia/reperfusion injury, thereby reducing cardiac infarct size, enhancing left ventricular function, and mitigating arrhythmias. These pleiotropic effects have demonstrated efficacy across various cardiovascular conditions, ranging from acute to chronic coronary syndromes and extending to arrhythmias, valvular heart disease, cardiomyopathies, cardio-oncology, and cerebrovascular disease.</div><div>This review provides an overview of the current literature on the potential mechanisms underlying the effectiveness of SGLT2 inhibitors across a wide range of cardiovascular diseases beyond HF.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"270 ","pages":"Article 108861"},"PeriodicalIF":12.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847843","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}

{"title":"Effect of cannabinoids on the efficacy and side effects of anticancer therapeutic strategies – Current status of preclinical and clinical research","authors":"Robert Ramer,&nbsp;Burkhard Hinz","doi":"10.1016/j.pharmthera.2025.108851","DOIUrl":"10.1016/j.pharmthera.2025.108851","url":null,"abstract":"<div><div>Cannabinoids have attracted increasing attention in cancer research in recent decades. A major focus of current preclinical and clinical studies is on the interactions and potential risks when combined with chemotherapeutic agents, targeted therapies and other anticancer strategies. Given the extensive preclinical data on additive, synergistic and, in some cases, antagonistic tumor cell killing effects of chemotherapeutic agents and cannabinoids when co-administered, a critical analysis of these data seems essential. The available data mainly relate to combination treatments for glioblastoma, hematological malignancies and breast cancer, but also for other cancer types. Such an analysis also appears necessary because cannabinoids are used as an option to treat nausea and vomiting caused by chemotherapy, as well as tumor-related pain, and cancer patients sometimes take cannabinoids without a medical prescription. In addition, numerous recent preclinical studies also suggest cannabinoid-mediated relief of other chemotherapy-related side effects such as peripheral neuropathy, nephrotoxicity, cardiotoxicity, cystitis, bladder complications and mucositis. To summarize, the data available to date raise the prospect that cannabinoids may increase the efficacy of chemotherapeutic agents while reducing their side effects. However, preclinical studies on anticancer interactions are mostly limited to cytotoxicity analyses. An equally thorough investigation of the effects of such combinations on the immune system and on the tumorigenic levels of angiogenesis, invasion and metastasis is still pending. On this basis, a comprehensive understanding for the evaluation of a targeted additional treatment of various cancers with cannabinoids could be established.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"270 ","pages":"Article 108851"},"PeriodicalIF":12.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868470","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}

{"title":"Resetting the aging clock through epigenetic reprogramming: Insights from natural products","authors":"Xin Liu ,&nbsp;Jing Feng ,&nbsp;Madi Guo ,&nbsp;Chen Chen ,&nbsp;Tong Zhao ,&nbsp;Xiuxiu Sun ,&nbsp;Yong Zhang","doi":"10.1016/j.pharmthera.2025.108850","DOIUrl":"10.1016/j.pharmthera.2025.108850","url":null,"abstract":"<div><div>Epigenetic modifications play a critical role in regulating gene expression under various physiological and pathological conditions. Epigenetic modifications reprogramming is a recognized hallmark of aging and a key component of the aging clock used to differentiate between chronological and biological age. The potential for prospective diagnosis and regulatory capabilities position epigenetic modifications as an emerging drug target to extend longevity and alleviate age-related organ dysfunctions. In the past few decades, numerous preclinical studies have demonstrated the therapeutic potential of natural products in various human diseases, including aging, with some advancing to clinical trials and clinical application. This review highlights the discovery and recent advancements in the aging clock, as well as the potential use of natural products as anti-aging therapeutics by correcting disordered epigenetic reprogramming. Specifically, the focus is on the imbalance of histone modifications, alterations in DNA methylation patterns, disrupted ATP-dependent chromatin remodeling, and changes in RNA modifications. By exploring these areas, new insights can be gained into aging prediction and anti-aging interventions.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"270 ","pages":"Article 108850"},"PeriodicalIF":12.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845023","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}