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Unveiling the macrophage dynamics in osteoarthritic joints: From inflammation to therapeutic strategies 揭示骨关节炎关节中巨噬细胞的动态变化：从炎症到治疗策略。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-19 DOI: 10.1016/j.drudis.2024.104187
Nicolas Gaigeard , Anaïs Cardon , Benoit Le Goff , Jérôme Guicheux , Marie-Astrid Boutet
{"title":"Unveiling the macrophage dynamics in osteoarthritic joints: From inflammation to therapeutic strategies","authors":"Nicolas Gaigeard ,&nbsp;Anaïs Cardon ,&nbsp;Benoit Le Goff ,&nbsp;Jérôme Guicheux ,&nbsp;Marie-Astrid Boutet","doi":"10.1016/j.drudis.2024.104187","DOIUrl":"10.1016/j.drudis.2024.104187","url":null,"abstract":"<div><div>Osteoarthritis (OA) is an incurable, painful, and debilitating joint disease affecting over 500 million people worldwide. The OA joint tissues are infiltrated by various immune cells, particularly macrophages, which are able to induce or perpetuate inflammation. Notably, synovitis and its macrophage component represent a target of interest for developing treatments. In this review, we describe the latest advances in understanding the heterogeneity of macrophage origins, phenotypes, and functions in the OA joint and the effect of current symptomatic therapies on these cells. We then highlight the therapeutic potential of anticytokines/chemokines, nano- and microdrug delivery, and future strategies to modulate macrophage functions in OA.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104187"},"PeriodicalIF":6.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
MAT2A inhibition combats metabolic and transcriptional reprogramming in cancer 抑制 MAT2A 可对抗癌症中的代谢和转录重编程。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-19 DOI: 10.1016/j.drudis.2024.104189
Fadi E. Pulous , Barbara Steurer , Frank W. Pun , Man Zhang , Feng Ren , Alex Zhavoronkov
{"title":"MAT2A inhibition combats metabolic and transcriptional reprogramming in cancer","authors":"Fadi E. Pulous ,&nbsp;Barbara Steurer ,&nbsp;Frank W. Pun ,&nbsp;Man Zhang ,&nbsp;Feng Ren ,&nbsp;Alex Zhavoronkov","doi":"10.1016/j.drudis.2024.104189","DOIUrl":"10.1016/j.drudis.2024.104189","url":null,"abstract":"<div><div>Metabolic and transcriptional reprogramming are crucial hallmarks of carcinogenesis that present exploitable vulnerabilities for the development of targeted anticancer therapies. Through controlling the balance of the cellular methionine (MET) metabolite pool, MET adenosyl transferase 2 alpha (MAT2A) regulates crucial steps during metabolism and the epigenetic control of transcription. The aberrant function of MAT2A has been shown to drive malignant transformation through metabolic addiction, transcriptional rewiring, and immune modulation of the tumor microenvironment (TME). Moreover, MAT2A sustains the survival of 5′-methylthioadenosine phosphorylase (MTAP)-deficient tumors, conferring synthetic lethality to cancers with MTAP loss, a genetic alteration that occurs in ∼15% of all cancers. Thus, the pharmacological inhibition of MAT2A is emerging as a desirable therapeutic strategy to combat tumor growth. Here, we review the latest insights into MAT2A biology, focusing on its roles in both metabolic addiction and gene expression modulation in the TME, outline the current landscape of MAT2A inhibitors, and highlight the most recent clinical developments and opportunities for MAT2A inhibition as a novel anti-tumor therapy.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104189"},"PeriodicalIF":6.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Beyond resmetirom approval for NAFLD: what has to be done? 非酒精性脂肪肝的雷美替罗批准之外：还需要做些什么？
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-19 DOI: 10.1016/j.drudis.2024.104185
Devaraj Ezhilarasan
{"title":"Beyond resmetirom approval for NAFLD: what has to be done?","authors":"Devaraj Ezhilarasan","doi":"10.1016/j.drudis.2024.104185","DOIUrl":"10.1016/j.drudis.2024.104185","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104185"},"PeriodicalIF":6.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Application of proteomics for novel drug discovery and risk prediction optimisation in stroke and myocardial infarction: a review of in-human studies 蛋白质组学在中风和心肌梗塞新药发现和风险预测优化中的应用：人体研究综述。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-19 DOI: 10.1016/j.drudis.2024.104186
Richard J. Webb , Maha Al-Asmakh , Maciej Banach , Mohsen Mazidi
{"title":"Application of proteomics for novel drug discovery and risk prediction optimisation in stroke and myocardial infarction: a review of in-human studies","authors":"Richard J. Webb ,&nbsp;Maha Al-Asmakh ,&nbsp;Maciej Banach ,&nbsp;Mohsen Mazidi","doi":"10.1016/j.drudis.2024.104186","DOIUrl":"10.1016/j.drudis.2024.104186","url":null,"abstract":"<div><div>The use of proteomics in human studies investigating stroke and myocardial infarction (MI) has been increasing, prompting a review of the literature. This revealed proteinaceous biomarkers of stroke from thrombi, brain tissue, cells, and particles, some of which cross the blood–brain barrier (BBB). Several proteins were also implicated in coronary artery disease (CAD), which often underlies MI, cholesterol transportation, and inflammation. Furthermore, the platelet proteome revealed itself as a potential therapeutic target, along with differentially expressed proteins associated with MI progression. Moreover, proteomic data enhanced the performance of conventional risk scores and causal protein discovery has improved interventions and drug development for patients with MI and other conditions. These findings suggest that proteomics holds much promise for future stroke and MI research.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104186"},"PeriodicalIF":6.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Early career researchers’ experiences in drug discovery in Africa 非洲早期职业研究人员在药物研发方面的经验。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-18 DOI: 10.1016/j.drudis.2024.104183
Godfrey Mayoka, Peter Mubanga Cheuka
{"title":"Early career researchers’ experiences in drug discovery in Africa","authors":"Godfrey Mayoka,&nbsp;Peter Mubanga Cheuka","doi":"10.1016/j.drudis.2024.104183","DOIUrl":"10.1016/j.drudis.2024.104183","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104183"},"PeriodicalIF":6.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Unveiling the potential of molecular imprinting polymer-based composites in the discovery of advanced drug delivery carriers 揭示分子印迹聚合物基复合材料在发现先进药物输送载体方面的潜力。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-16 DOI: 10.1016/j.drudis.2024.104164
Amit Kumar , Shashi Kashyap , Farhan Mazahir , Rajeev Sharma , Awesh K. Yadav
{"title":"Unveiling the potential of molecular imprinting polymer-based composites in the discovery of advanced drug delivery carriers","authors":"Amit Kumar ,&nbsp;Shashi Kashyap ,&nbsp;Farhan Mazahir ,&nbsp;Rajeev Sharma ,&nbsp;Awesh K. Yadav","doi":"10.1016/j.drudis.2024.104164","DOIUrl":"10.1016/j.drudis.2024.104164","url":null,"abstract":"<div><div>Molecularly imprinted polymers (MIPs) are polymeric matrices that can mimic natural recognition entities, such as antibodies and biological receptors. Molecular imprinting of therapeutics is very appealing in the design of drug delivery systems since the specific and selective binding sites created within the polymeric matrix turn these complex structures into value-added carriers with tunable features, notably high drug-loading capacity and good control of payload release. MIPs possess considerable promise as synthetic recognition elements in ‘theranostics’. Moreover, the high affinity and specificity of MIPs make them more advantageous than other polymer-based nanocomposites. This review summarizes the present state-of-the-art of MIP-based delivery systems for the targeted delivery of bioactives, with current challenges and future perspectives.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104164"},"PeriodicalIF":6.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 regulatory mechanism of natural polysaccharides in type 2 diabetes mellitus treatment 天然多糖在 2 型糖尿病治疗中的调节机制
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-14 DOI: 10.1016/j.drudis.2024.104182
Surina Bo , Mu Dan , Wei Li , Chen Chen
{"title":"The regulatory mechanism of natural polysaccharides in type 2 diabetes mellitus treatment","authors":"Surina Bo ,&nbsp;Mu Dan ,&nbsp;Wei Li ,&nbsp;Chen Chen","doi":"10.1016/j.drudis.2024.104182","DOIUrl":"10.1016/j.drudis.2024.104182","url":null,"abstract":"<div><div>Diabetes is a complex, multifactorial disease that is caused by a pathological combination of insulin resistance and pancreatic islet dysfunction. Polysaccharides are extensively dispersed in nature and have a very complicated structure with various biological properties. Natural polysaccharides have potentially extraordinary beneficial health effects on managing metabolic diseases such as diabetes, obesity and cardiovascular disease. Thus, a systematic review of the latest research into and possible regulatory mechanisms of natural polysaccharides for type 2 diabetes mellitus treatment is of great significance for a better understanding of their pharmaceutical value. We discuss the regulatory mechanisms of natural polysaccharides for the treatment of diabetes, and especially their role in reshaping dysfunctional gut microbiota. Natural polysaccharides could be developed as new and safe antidiabetic drugs, and detailed mechanistic studies could further clarify the molecular targets of polysaccharides in the treatment of diabetes.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104182"},"PeriodicalIF":6.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624003076/pdfft?md5=0e0518270b681b81f1885e4f5c0b10f9&pid=1-s2.0-S1359644624003076-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Regulatory readiness to facilitate the appropriate use of innovation in clinical trials: The case of decentralized clinical trial approaches 为促进在临床试验中适当利用创新做好监管准备：分散式临床试验方法
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-14 DOI: 10.1016/j.drudis.2024.104180
Amos J. de Jong , Mira G.P. Zuidgeest , Yared Santa-Ana-Tellez , Anthonius de Boer , Helga Gardarsdottir , the Trials@Home Consortium
{"title":"Regulatory readiness to facilitate the appropriate use of innovation in clinical trials: The case of decentralized clinical trial approaches","authors":"Amos J. de Jong ,&nbsp;Mira G.P. Zuidgeest ,&nbsp;Yared Santa-Ana-Tellez ,&nbsp;Anthonius de Boer ,&nbsp;Helga Gardarsdottir ,&nbsp;the Trials@Home Consortium","doi":"10.1016/j.drudis.2024.104180","DOIUrl":"10.1016/j.drudis.2024.104180","url":null,"abstract":"<div><div>Methodological and operational clinical trial innovation is needed to address key challenges associated with clinical trials, including limited generalizability and (s)low recruitment rates. In this article, we discuss how appropriate implementation of innovative clinical trial approaches can be facilitated by a timely identification of, and response to, emerging situations and innovation by regulators (i.e. regulatory readiness) using decentralized clinical trial (DCT) approaches – in which trial activities are moved closer to participants and away from the investigative sites – as a case study example. Specifically, we discuss how explorative research (e.g. using regulatory sandboxes) can enable the collection of data on the usefulness of DCT approaches. Additionally, we argue that DCT approaches should be evaluated similarly to conventional clinical trials.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104180"},"PeriodicalIF":6.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624003052/pdfft?md5=54070be5f10ff3de1fbc2a29a874ccde&pid=1-s2.0-S1359644624003052-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Expression, regulation, and function of PD-L1 on non-tumor cells in the tumor microenvironment 肿瘤微环境中非肿瘤细胞上 PD-L1 的表达、调节和功能
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-13 DOI: 10.1016/j.drudis.2024.104181
Lingrong Hu , Chengliang Sun , Kai Yuan , Peng Yang
{"title":"Expression, regulation, and function of PD-L1 on non-tumor cells in the tumor microenvironment","authors":"Lingrong Hu ,&nbsp;Chengliang Sun ,&nbsp;Kai Yuan ,&nbsp;Peng Yang","doi":"10.1016/j.drudis.2024.104181","DOIUrl":"10.1016/j.drudis.2024.104181","url":null,"abstract":"<div><div>Antiprogrammed death ligand 1 (PD-L1) therapy is a leading immunotherapy, but only some patients with solid cancers benefit. Overwhelming evidence has revealed that PD-L1 is expressed on various immune cells in the tumor microenvironment (TME), including macrophages, dendritic cells, and regulatory T cells, modulating tumor immunity and influencing tumor progression. PD-L1 can also be located on tumor cell membranes as well as in exosomes and cytoplasm. Accordingly, the dynamic expression and various forms of PD-L1 might explain the therapy’s limited efficacy and resistance. Herein a systematic summary of the expression of PD-L1 on different immune cells and their regulatory mechanisms is provided to offer a solid foundation for future studies.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104181"},"PeriodicalIF":6.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
MicroRNAs and therapeutic potentials in acute and chronic cardiac disease 急性和慢性心脏病中的微 RNA 和治疗潜力
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-12 DOI: 10.1016/j.drudis.2024.104179
Rui Song, Lubo Zhang
{"title":"MicroRNAs and therapeutic potentials in acute and chronic cardiac disease","authors":"Rui Song,&nbsp;Lubo Zhang","doi":"10.1016/j.drudis.2024.104179","DOIUrl":"10.1016/j.drudis.2024.104179","url":null,"abstract":"<div><p>microRNAs (miRNAs) are small regulatory RNAs implicated in various cardiac disorders. In this review, the role of miRNAs is discussed in relation to acute myocardial infarction and chronic heart failure. In both settings, miRNAs are altered, contributing to injury and adverse remodeling. Notably, miRNA profiles differ between acute ischemic injury and progressive heart failure. Owing to miRNA variabilities between disease stages and delivery difficulties, translation of animal studies to the clinic remains challenging. The identification of distinct miRNA signatures could lead to the development of miRNA therapies tailored to different disease stages. Here, we summarize the current understanding of miRNAs in acute and chronic cardiac diseases, identify knowledge gaps and discuss progress in developing miRNA-based treatment strategies.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104179"},"PeriodicalIF":6.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624003040/pdfft?md5=0a00fedfa19b4c6cd48de16392cfbb81&pid=1-s2.0-S1359644624003040-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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