Pharmacology & Therapeutics最新文献

{"title":"G protein-coupled estrogen receptor biased signaling in health and disease","authors":"Aisha Bushi ,&nbsp;Yixuan Ma ,&nbsp;Joseph Adu-Amankwaah ,&nbsp;Rong Wang ,&nbsp;Fen Cui ,&nbsp;Rui Xiao ,&nbsp;Jinming Zhao ,&nbsp;Jinxiang Yuan ,&nbsp;Rubin Tan","doi":"10.1016/j.pharmthera.2025.108822","DOIUrl":"10.1016/j.pharmthera.2025.108822","url":null,"abstract":"<div><div>G protein-coupled estrogen receptor (GPER) is now recognized for its pivotal role in cellular signaling, influencing diverse physiological processes and disease states. Unlike classical estrogen receptors, GPER exhibits biased signaling, wherein ligand binding triggers selective pathways over others, significantly impacting cellular responses. This review explores the nuanced mechanisms of biased signaling mediated by GPER, underscoring its relevance in cardiovascular health, neurological function, immune modulation, and oncogenic processes. Despite its critical implications, biased signaling through GPER remains underexplored compared to traditional signaling paradigms. We explore recent progress in understanding GPER signaling specificity and its potential therapeutic implications across various diseases. Future research directions aim to uncover the molecular basis of biased signaling, develop selective ligands, and translate these insights into personalized therapeutic approaches. Exploiting the therapeutic potential of GPER biased signaling represents a promising frontier in precision medicine, offering innovative strategies to address unmet medical needs.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108822"},"PeriodicalIF":12.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466518","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":"The tumor suppressor role and epigenetic regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in cancer and tumor microenvironment (TME)","authors":"SubbaRao V. Tulimilli ,&nbsp;Medha Karnik ,&nbsp;Anjali Devi S. Bettadapura ,&nbsp;Olga A. Sukocheva ,&nbsp;Edmund Tse ,&nbsp;Gowthamarajan Kuppusamy ,&nbsp;Suma M. Natraj ,&nbsp;SubbaRao V. Madhunapantula","doi":"10.1016/j.pharmthera.2025.108826","DOIUrl":"10.1016/j.pharmthera.2025.108826","url":null,"abstract":"<div><div>Oxidative stress and inflammation may initiate carcinogenesis and facilitate metastasis <em>via</em> activation of pro-inflammatory signaling network. The side product of arachidonic acid processing by cyclooxygenase-2 (COX-2), the prostaglandin E2 (PGE2), plays a key role in various metabolic disorders and during inflammation-mediated tumorigenesis. It has been demonstrated that PGE2 increases the proliferation, migration, invasion, metastasis, and resistance of cancer cells to apoptosis and other forms of programmed cell death. The expression level of PGE2 metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is often decreased in various malignancies. However, the role of 15-PGDH and PGE2 in the regulation of carcinogenesis remains controversial. Numerous cancer cell lines and mouse models have demonstrated the role of 15-PGDH as a tumor suppressor. Downregulation of 15-PGDH increased cancer cell proliferation, migration, anchorage independent growth, colony formation while overexpression reversed these effects, by inducing apoptosis and cell cycle arrest <em>in vitro</em> and <em>in vivo</em>. The expression of 15-PGDH is regulated by various mechanisms, including (a) epigenetic alterations (methylation of promoter region, histone deacetylases, microRNAs (miR-21, miR-26a/b, miR-106b-5p, miR-146b-3p, miR-155, miR-218-5p, and miR-620)); and (b) dysregulated oxidative stress and associated mediators (elevated levels of growth factors and proinflammatory cytokines (such as IL1β and TNFα)). Several transcription factors, such as HNF3β, β-catenin, Snail, Slug, can bind to 15-PGDH promoter region and downregulate the enzyme expression. In contrast, the expression of 15-PGDH can be upregulated by several anti-inflammatory cytokines and anti-cancer agents, such as IL10 and vitamin D. The functional activity of 15-PGDH protein can be modulated by signaling effectors and oxidative stress, including increased production of reactive oxygen species (ROS). However, the role of oxidative stress regulator protein, <em>i.e.</em>, nuclear factor erythroid 2-related factor 2 (Nrf2), in the control of 15-PGDH expression remains unclear. This article provides insights and comprehensive overview of the tumor suppressor role of 15-PGDH in various cancers. Epigenetic and post-translational mechanisms regulating 15-PGDH expression and the role of novel ROS-Nrf2–15-PGDH axis were discussed and accented as potential drug targets.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"268 ","pages":"Article 108826"},"PeriodicalIF":12.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456386","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":"Biomarker identification in bipolar disorder","authors":"Francesca Martella ,&nbsp;Andrea Caporali ,&nbsp;Monica Macellaro ,&nbsp;Rita Cafaro ,&nbsp;Francesco De Pasquale ,&nbsp;Bernardo Dell'Osso ,&nbsp;Claudio D'Addario","doi":"10.1016/j.pharmthera.2025.108823","DOIUrl":"10.1016/j.pharmthera.2025.108823","url":null,"abstract":"<div><div>Bipolar disorder (BD) is a severe psychiatric condition whose pathophysiology is complex and multifactorial. Genetic, environmental and social risk factors play a role in its development as well as in its progressive course. Research is currently focusing on the identification of the biological basis underlying these processes in order to suggest novel biomarkers capable to predict BD etiopathogenesis and staging. Staging has been recognized as of great value for the treatment and management of many illnesses and might also be suitable for mental health issues, particularly in disorders like BD, which progress from an initial mild phase to a more severe and thus difficult-to-treat situation. Thus, it would be of great help the characterization of to suggest better treatment requirements and improve prognosis across the different stages of the illness. Here, we summarize current research on the biological hypotheses of BD and the biomarkers associated with its progression, reviewing clinical studies available in the literature.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"268 ","pages":"Article 108823"},"PeriodicalIF":12.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444735","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":"Biased signaling by human follicle-stimulating hormone variants","authors":"Alfredo Ulloa-Aguirre ,&nbsp;Teresa Zariñán ,&nbsp;James A. Dias ,&nbsp;T. Rajendra Kumar ,&nbsp;George R. Bousfield","doi":"10.1016/j.pharmthera.2025.108821","DOIUrl":"10.1016/j.pharmthera.2025.108821","url":null,"abstract":"<div><div>Follicle-stimulating hormone (FSH) or follitropin plays a fundamental role in several mammalian species, including humans. This gonadotropin is produced by the anterior pituitary gland and has as its main targets the granulosa cells of the ovary and the Sertoli cells of the testis. Structurally, FSH is composed of two non-convalently linked subunits, the α- and β-subunit, as well as highly heterogenous oligosaccharide structures, which play a key role in determining a number of physiological and biological features of the hormone. Glycosylation in FSH and the other members belonging to the glycoprotein hormone family, is essential for many functions of the gonadotropin, including subunit assembly and stability, secretion, circulatory half-life and biological activity. Carbohydrate heterogeneity in FSH comes in two forms, <em>microheterogeneity,</em> which results from variations in the carbohydrate structural complexity in those oligosaccharides attached to the α- or β-subunit of the hormone and <em>macroheterogeneity</em>, which results from the absence of carbohydrate chain at FSHβ Asn-glycosylation sites. A number of <em>in vitro</em> and <em>in vivo</em> studies have conclusively demonstrated differential, unique and even opposing effects provoked by variations in the carbohydrate structures of FSH, including circulatory survival, binding to and activation of its cognate receptor in the gonads, intracellular signaling, and activation/inhibition of a number of FSH-regulated genes essential for follicle development. Herein, we review the effects of the FSH oligosaccharides on several functions of FSH, and how variations in these structures have been shown to lead to functional selectivity of the hormone.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"268 ","pages":"Article 108821"},"PeriodicalIF":12.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439724","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 PCSK9 targeting: Inside versus outside the hepatocyte?","authors":"Alberto Corsini ,&nbsp;Henry N. Ginsberg ,&nbsp;M. John Chapman","doi":"10.1016/j.pharmthera.2025.108812","DOIUrl":"10.1016/j.pharmthera.2025.108812","url":null,"abstract":"<div><div>As a major regulator of LDL receptor (LDLR) activity and thus of LDL-cholesterol (LDL-C) levels, proprotein convertase subtilisin/kexin type 9 (PCSK9) represents an obvious therapeutic target for lipid lowering. The PCSK9 inhibitors, alirocumab and evolocumab, are human monoclonal antibodies (mAbs) that act outside the cell by complexing circulating PCSK9 and thus preventing its binding to the LDLR. In contrast, inclisiran, a small interfering RNA (siRNA), inhibits hepatic synthesis of PCSK9, thereby resulting in reduced amounts of the protein inside and outside the cell. Both approaches result in decreased plasma LDL-C concentrations and improved cardiovascular outcomes. Marginally superior LDL-C reduction (≈ 60 %) is achieved with mAbs as compared to the siRNA (≈ 50 %); head-to-head comparisons are required to confirm between-class differences in efficacy. Both drug classes have shown variability in LDL-C lowering response between individuals in waterfall analyses. Whereas mAb-mediated inhibition leads to a compensatory increase in plasma PCSK9 levels, siRNA treatment reduces them. These agents differ in their pharmacokinetic and pharmacodynamic features, which may translate into distinct clinical opportunities under acute (e.g. acute coronary syndromes) as compared to chronic conditions. Both drug classes provide additional reduction in LDL-C levels (up to 50 %) beyond those achieved with statin therapy, facilitating attainment of guideline-recommended LDL-C goals in high and very high-risk patients. Additional PCSK9 inhibitors, including an oral macrocyclic peptide, a small PCSK9 binding protein and a novel small molecule, plus hepatic gene editing of PCSK9, are under development. This review critically appraises pharmacological strategies to target PCSK9 either inside or outside the cell.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"268 ","pages":"Article 108812"},"PeriodicalIF":12.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412738","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}

{"title":"Insights into the results of Resmetirom trials: Can a thyroid hormone receptor agonist be the holy grail of MASH therapy?","authors":"Konstantinos Arvanitakis ,&nbsp;Theocharis Koufakis ,&nbsp;Evangelos Cholongitas ,&nbsp;Sven Francque ,&nbsp;Georgios Germanidis","doi":"10.1016/j.pharmthera.2025.108811","DOIUrl":"10.1016/j.pharmthera.2025.108811","url":null,"abstract":"<div><div>Despite the heavy individual patient and socioeconomic burden of metabolic dysfunction-associated steatohepatitis (MASH), until recently, no pharmacological therapy for MASH was approved, with available treatment options geared towards associated cardiometabolic risk factors. Accelerated approval of resmetirom, a thyroid hormone receptor-β agonist to be used in conjunction with diet and exercise, marks a significant step forward in the treatment of MASH, offering tempered optimism to healthcare providers and millions of patients around the world for more effective management. Evidence from phase 2 and 3 clinical trials suggests that resmetirom has the potential to alleviate hepatic fibrosis and inflammation and significantly reduce liver lipid content. Notwithstanding this landmark event, the clinical implementation of resmetirom comes with important challenges, for example, ensuring patient access to treatment and demonstrating effects on hard MASH-related outcomes, such as progression to cirrhosis and hepatocellular carcinoma. Additional considerations include the evaluation of co-administration with other hepatoprotective treatments and the assessment of the efficacy in specific MASH sub-phenotypes. Furthermore, the accumulation of real-world data and experience is expected to help answer the remaining questions about the (long-term) effectiveness and safety profile of the drug. The purpose of this article is to provide an updated and critical review of the mechanisms of action, efficacy, and safety of resmetirom based on the latest clinical trials, to define its place within the broader landscape of MASH management, and to highlight current knowledge gaps and opportunities for future research in the field.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"268 ","pages":"Article 108811"},"PeriodicalIF":12.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404995","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}

{"title":"From barbiturates to ganaxolone: The importance of chirality in drug development and in understanding the actions of old and new antiseizure medications","authors":"Meir Bialer ,&nbsp;Emilio Perucca","doi":"10.1016/j.pharmthera.2025.108808","DOIUrl":"10.1016/j.pharmthera.2025.108808","url":null,"abstract":"<div><div>Out of 37 antiseizure medications (ASMs) currently in the market, 17 are chiral molecules and an additional one (oxcarbazepine) is a prodrug of the chiral compound licarbazepine. Of the 17 chiral ASMs, six (ethosuximide, fenfluramine, methsuximide, mephobarbital, stiripentol and vigabatrin) are marketed as racemates, and the remainder are licensed as enantiomerically pure medicines. Of note, all chiral ASMs introduced prior to 1990 were marketed as racemates. Stiripentol, fenfluramine and vigabatrin are the only racemic ASMs approved by the FDA &gt;10 years after the release of regulatory guidelines on the development of chiral medicines. Despite the fact that pharmacokinetic and pharmacodynamic differences between enantiomers have been recognized for decades, the importance of chirality in understanding the biological actions of ASMs is not widely appreciated, and many recent publications on racemic ASMs refer to these medications as if they were a single molecular entity. In the present article, we provide a critical review of chiral ASMs developed between the 1920s, when mephobarbital was introduced, and 2022, when the last chiral ASM (ganaxolone) was approved. We summarize available data on stereoselective differences in pharmacokinetics and pharmacodynamics of ASMs marketed as racemates. We also discuss regulatory aspects related to the introduction of racemic medicines within the current regulatory scenario in Europe and the U.S., focusing on stiripentol, vigabatrin and fenfluramine as examples of different approaches. We identified a number of critical knowledge gaps that are relevant to the use of chiral drugs in epilepsy, including a remarkable lack of published information on the comparative pharmacokinetics, toxicity and antiseizure activity of the enantiomers of most racemic ASMs. The importance of chirality aspects in understanding the clinical actions of racemic ASMs is discussed, together with the rationale for the development of enantiomerically pure follow-up compounds with potentially improved efficacy, safety and commercial viability.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"268 ","pages":"Article 108808"},"PeriodicalIF":12.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373619","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}

{"title":"Understanding the molecular bridges between the drugs and immune cell","authors":"Umesh Chandra Dash ,&nbsp;Vinayak Nayak ,&nbsp;Hiten Shanker Navani ,&nbsp;Rashmi Rekha Samal ,&nbsp;Palak Agrawal ,&nbsp;Anup Kumar Singh ,&nbsp;Sanatan Majhi ,&nbsp;Devraj Ganpat Mogare ,&nbsp;Asim K. Duttaroy ,&nbsp;Atala Bihari Jena","doi":"10.1016/j.pharmthera.2025.108805","DOIUrl":"10.1016/j.pharmthera.2025.108805","url":null,"abstract":"<div><div>The interactions of drugs with the host's immune cells determine the drug's efficacy and adverse effects in patients. Nonsteroidal Anti-Inflammatory Drugs (NSAID), such as corticosteroids, NSAIDs, and immunosuppressants, affect the immune cells and alter the immune response. Molecularly, drugs can interact with immune cells via cell surface receptors, changing the antigen presentation by modifying the co-stimulatory molecules and interacting with the signaling pathways of T cells, B cells, Natural killer (NK) cells, mast cells, basophils, and macrophages. Immunotoxicity, resulting from drug-induced changes in redox status, generation of Reactive Oxygen Species (ROS)/Reactive Nitrogen Species (RNS), and alterations in antioxidant enzymes within immune cells, leads to immunodeficiency. This, in turn, causes allergic reactions, autoimmune diseases, and cytokine release syndrome (CRS). The treatment options should include the evaluation of immune status and utilization of the concept of pharmacogenomics to minimize the chances of immunotoxicity. Many strategies in redox, like targeting the redox pathway or using redox-active agents, are available for the modulation of the immune system and developing drugs. Case studies highlight significant drug-immune cell interactions and patient outcomes, underscoring the importance of understanding these complexities. The future direction focuses on the drugs to deliver antiviral therapy, new approaches to immunomodulation, and modern technologies for increasing antidote effects with reduced toxicity. In conclusion, in-depth knowledge of the interaction between drugs and immune cells is critical to protect the patient from the adverse effects of the drug and improve therapeutic outcomes of the treatment process. This review focuses on the multifaceted interactions of drugs and their consequences at the cellular levels of immune cells.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"267 ","pages":"Article 108805"},"PeriodicalIF":12.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143137321","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}

{"title":"Targeting TAK1: Evolution of inhibitors, challenges, and future directions","authors":"Nika Strašek Benedik ,&nbsp;Matic Proj ,&nbsp;Christian Steinebach ,&nbsp;Matej Sova ,&nbsp;Izidor Sosič","doi":"10.1016/j.pharmthera.2025.108810","DOIUrl":"10.1016/j.pharmthera.2025.108810","url":null,"abstract":"<div><div>The increasing incidence of inflammatory and malignant diseases signifies the need to develop first-in-class drugs with novel mechanisms of action. In this respect, the transforming growth factor (TGF)-β-activated kinase 1 (TAK1), an essential part of several signaling pathways, is considered relevant and promising. This manuscript provides a brief overview of the signal transduction orchestrated by TAK1 within these pathways, followed by an in-depth and thorough analysis of the chemical matter demonstrated to inhibit this kinase. Special attention is given to the selectivity profiling of inhibitors, as well as to the outcomes of their biological characterization. Because published TAK1 inhibitors differ significantly in their kinome selectivity, active-site binding, and biological activity, we hope that this review will allow a judicial estimation of their quality and usefulness for TAK1-addressing assays. Our thoughts on the perspectives and possible developments of the field are also provided to assist scientists who are involved in the design and development of TAK1-targeting modulators.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"267 ","pages":"Article 108810"},"PeriodicalIF":12.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254028","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}

{"title":"Biased signaling in drug discovery and precision medicine","authors":"Ren-Lei Ji,&nbsp;Ya-Xiong Tao","doi":"10.1016/j.pharmthera.2025.108804","DOIUrl":"10.1016/j.pharmthera.2025.108804","url":null,"abstract":"<div><div>Receptors are crucial for converting chemical and environmental signals into cellular responses, making them prime targets in drug discovery, with about 70% of drugs targeting these receptors. Biased signaling, or functional selectivity, has revolutionized drug development by enabling precise modulation of receptor signaling pathways. This concept is more firmly established in G protein-coupled receptor and has now been applied to other receptor types, including ion channels, receptor tyrosine kinases, and nuclear receptors. Advances in structural biology have further refined our understanding of biased signaling. This targeted approach enhances therapeutic efficacy and potentially reduces side effects. Numerous biased drugs have been developed and approved as therapeutics to treat various diseases, demonstrating their significant therapeutic potential. This review provides a comprehensive overview of biased signaling in drug discovery and disease treatment, highlighting recent advancements and exploring the therapeutic potential of these innovative modulators across various diseases.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"268 ","pages":"Article 108804"},"PeriodicalIF":12.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187876","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}