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ECM stiffness and epigenetics in organ fibrosis. 器官纤维化的ECM僵硬和表观遗传学。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-01 Epub Date: 2026-06-10 DOI: 10.1016/j.tips.2026.05.009
Peng Zhao, Shi Yin, Hui Tao
{"title":"ECM stiffness and epigenetics in organ fibrosis.","authors":"Peng Zhao, Shi Yin, Hui Tao","doi":"10.1016/j.tips.2026.05.009","DOIUrl":"10.1016/j.tips.2026.05.009","url":null,"abstract":"<p><p>Extracellular matrix stiffness drives fibrosis via DNA methylation, histone modifications, and non-coding RNAs. These epigenetic nodes translate mechanical cues into persistent fibrotic memory. This forum article consolidates recent advances in this mechano-epigenetic axis.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"720-725"},"PeriodicalIF":24.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148219842","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
Which HTT transcript to lower? 要降低哪个HTT转录本？
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-01 Epub Date: 2026-06-09 DOI: 10.1016/j.tips.2026.05.008
Min Zhang
{"title":"Which HTT transcript to lower?","authors":"Min Zhang","doi":"10.1016/j.tips.2026.05.008","DOIUrl":"10.1016/j.tips.2026.05.008","url":null,"abstract":"<p><p>Huntington's disease (HD) RNA therapeutics have focused on lowering canonical huntingtin (HTT), yet clinical benefit remains uncertain. Papadopoulou et al. and Bragg et al. suggest that HTT1a-engaging strategies can produce stronger molecular rescue than full-length HTT lowering that spares HTT1a, highlighting transcript-species coverage as a key variable in HTT-lowering pharmacology.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"717-719"},"PeriodicalIF":24.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212588","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
GPR35 in host-microbe interaction: Mechanisms and translational prospects. 宿主-微生物相互作用中的GPR35：机制和翻译前景。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-01 Epub Date: 2026-06-04 DOI: 10.1016/j.tips.2026.05.007
Jian Chen, Xiaoying Cai, Qingyun Ma, Haiping Hao, Xiao Zheng
{"title":"GPR35 in host-microbe interaction: Mechanisms and translational prospects.","authors":"Jian Chen, Xiaoying Cai, Qingyun Ma, Haiping Hao, Xiao Zheng","doi":"10.1016/j.tips.2026.05.007","DOIUrl":"10.1016/j.tips.2026.05.007","url":null,"abstract":"<p><p>Understanding the mechanism of host-microbe interaction expands the landscape of drug discovery. Challenges, however, exist in the discovery of druggable targets from their signaling network. G protein-coupled receptors are versatile sensors at the host-microbe interface, and G protein-coupled receptor 35 (GPR35) is increasingly shown to play a role via metabolic, immune, and neural mechanisms. These advances not only enrich the pharmacology of this orphan receptor but also suggest an alternative path for microbiome-based therapeutics. We update the knowledge on GPR35-mediated host-microbe interaction in health and disease. We discuss the need to probe endogenous ligands of GPR35 with pathophysiological and human relevance, highlighting the complexities from species selectivity and signaling bias. We also propose potential strategies to translate the emerging insights into therapeutics with a balanced efficacy and safety profile.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"772-786"},"PeriodicalIF":24.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164722","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-quality-guided AI strategies for natural product drug discovery. 天然产物药物发现的数据质量导向人工智能策略。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-01 Epub Date: 2026-05-18 DOI: 10.1016/j.tips.2026.04.008
Sang-Seop Lee, Yung-Choon Yoo
{"title":"Data-quality-guided AI strategies for natural product drug discovery.","authors":"Sang-Seop Lee, Yung-Choon Yoo","doi":"10.1016/j.tips.2026.04.008","DOIUrl":"10.1016/j.tips.2026.04.008","url":null,"abstract":"<p><p>The component specification problem-the mismatch between bioactivity observed in chemically unresolved extracts and the constituent-level chemical definition required for reliable artificial intelligence (AI) inference-remains a key bottleneck in computational natural product (NP) discovery. Without operational standards linking analytical evidence to AI strategy, even sophisticated models risk overinterpretation when applied to incompletely resolved extracts. Here, we introduce a data-quality-guided framework that aligns AI approaches with Metabolomics Standards Initiative (MSI) identification tiers. Informed by emerging case studies across MSI levels, this strategy enables researchers to match computational tools to available analytical resolution rather than exceed it. By integrating ethnopharmacological knowledge and multi-omics validation, the framework positions AI as a calibrated decision-support instrument for translational NP research.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"726-742"},"PeriodicalIF":24.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975613","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
Remibrutinib (Rhapsido) for chronic spontaneous urticaria. Remibrutinib （Rhapsido）治疗慢性自发性荨麻疹。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-01 Epub Date: 2026-05-22 DOI: 10.1016/j.tips.2026.05.001
Erica N Lamkin, Eduardo Bravo, Justin Taylor
{"title":"Remibrutinib (Rhapsido) for chronic spontaneous urticaria.","authors":"Erica N Lamkin, Eduardo Bravo, Justin Taylor","doi":"10.1016/j.tips.2026.05.001","DOIUrl":"10.1016/j.tips.2026.05.001","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"816-817"},"PeriodicalIF":24.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989096","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
AI-guided prediction of ncRNA biochemical features for therapeutic targeting. 人工智能引导的ncRNA生化特征预测用于靶向治疗。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-01 Epub Date: 2026-06-09 DOI: 10.1016/j.tips.2026.05.004
Jun Wei Chan, Ciarán W P Daly, Amhed Missael Vargas-Velazquez, Pierce K H Chow, Jinmiao Chen, Vinay Tergaonkar
{"title":"AI-guided prediction of ncRNA biochemical features for therapeutic targeting.","authors":"Jun Wei Chan, Ciarán W P Daly, Amhed Missael Vargas-Velazquez, Pierce K H Chow, Jinmiao Chen, Vinay Tergaonkar","doi":"10.1016/j.tips.2026.05.004","DOIUrl":"10.1016/j.tips.2026.05.004","url":null,"abstract":"<p><p>Noncoding RNAs (ncRNAs) are increasingly recognized as important therapeutic targets across human diseases, driving advances in RNA-targeting modalities. However, successful therapeutic engagement depends on key biochemical properties of the target ncRNA, including subcellular localization, higher-order structure, and accessibility, which influence the suitability of different RNA-targeting modalities. Historically, resolving these properties relied on labor-intensive experimentation, limiting rational prioritization of RNA-targeting modalities. Emerging artificial intelligence (AI) tools can now predict ncRNA biochemical features at scale, enabling systematic characterization of target properties relevant to therapeutic design. In this opinion article, we outline AI approaches for predicting ncRNA localization, structure, and accessibility, including deep learning models, RNA structural predictors, and therapeutic prioritization frameworks. We discuss how these tools may support informed selection of RNA-targeting modalities, while highlighting current limitations and future opportunities for AI-guided therapeutic development.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"743-759"},"PeriodicalIF":24.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206189","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
Engineering early immune resilience in islet transplantation. 胰岛移植的早期免疫恢复工程。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-01 Epub Date: 2026-06-09 DOI: 10.1016/j.tips.2026.05.006
Yuqi Li, Naschla Gasaly, Jonathan R T Lakey, Gorka Orive, Paul de Vos
{"title":"Engineering early immune resilience in islet transplantation.","authors":"Yuqi Li, Naschla Gasaly, Jonathan R T Lakey, Gorka Orive, Paul de Vos","doi":"10.1016/j.tips.2026.05.006","DOIUrl":"10.1016/j.tips.2026.05.006","url":null,"abstract":"<p><p>Pancreatic islet transplantation holds the promise of restoring natural insulin control in type 1 diabetes, yet most transplanted islets are destroyed within hours by the instant blood-mediated inflammatory reaction (IBMIR), a thrombo-inflammatory burst that has long limited clinical success. This early barrier matters because it prevents durable graft function even when immunosuppression is optimal. Recent advances in pharmacological and cell-intrinsic interventions, biomaterial-based modulation, and the strategic use of extrahepatic transplant sites have begun to transform our ability to modulate this reaction. This review integrates these developments to reposition IBMIR as a targetable and mechanistically understood process. We provide a forward-looking synthesis that outlines how converging technologies can build an immune-resilient microenvironment for durable, scalable islet transplantation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"787-801"},"PeriodicalIF":24.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212618","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
Chronobiomaterials for circadian-aligned brain therapeutics. 用于符合昼夜节律的脑治疗的时间生物材料。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-01 Epub Date: 2026-06-12 DOI: 10.1016/j.tips.2026.05.005
Shubham Garg, Burgundy Walters, Diego C Fernandez
{"title":"Chronobiomaterials for circadian-aligned brain therapeutics.","authors":"Shubham Garg, Burgundy Walters, Diego C Fernandez","doi":"10.1016/j.tips.2026.05.005","DOIUrl":"10.1016/j.tips.2026.05.005","url":null,"abstract":"<p><p>Circadian rhythms are endogenous ~24 h oscillations that regulate daily changes in neural activity, metabolism, and behavior. Disruption of circadian rhythms is a hallmark of neurological and psychiatric disorders, yet most brain-directed therapies use fixed dosing schedules that do not account for time-of-day variations in drug efficacy and toxicity. Recent advances in bioengineering have led to the development of chronobiomaterials-including nanoparticles, exosomes, hydrogels, cell-based systems, and bioelectronic interfaces-that enable programmable and temporally precise control of therapeutic delivery. Here, we describe the multiscale organization of cellular and molecular circadian clocks in the brain, review chronobiomaterial platforms designed to modulate circadian phase, amplitude, and period, and discuss AI-enabled closed-loop approaches for personalized chronotherapy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"802-815"},"PeriodicalIF":24.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240290","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
Biosensors for translatable GPCR bias. 可翻译GPCR偏倚的生物传感器。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-07-01 Epub Date: 2026-06-12 DOI: 10.1016/j.tips.2026.05.010
Ren-Lei Ji, Ya-Xiong Tao
{"title":"Biosensors for translatable GPCR bias.","authors":"Ren-Lei Ji, Ya-Xiong Tao","doi":"10.1016/j.tips.2026.05.010","DOIUrl":"10.1016/j.tips.2026.05.010","url":null,"abstract":"<p><p>Biased agonism at G protein-coupled receptors (GPCRs) is increasingly pursued to improve efficacy-safety relationships, but its translation remains limited by assay-dependent definitions of selectivity. Recent biosensors now resolve GPCR signaling across mechanistic layers that older endpoint assays often miss, including receptor conformational dynamics, heterotrimeric G protein coupling, Gα-GTP formation, β-arrestin and G protein-coupled receptor kinase engagement, activation trajectories, and signaling from intracellular compartments. Open and scalable platforms support comparative profiling, whereas more orthogonal unimolecular and endogenous-compatible systems improve mechanistic attribution and physiological relevance. Together with recent receptor-proximal studies, these advances indicate that bias should be treated as graded evidence rather than a binary label. In this opinion article, we discuss how biosensors convert assay-local signatures into translatable pharmacological evidence.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"760-771"},"PeriodicalIF":24.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240328","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
July 2026 issue first authors. 2026年7月号第一作者。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-20 DOI: 10.1016/j.tips.2026.06.001
Ren-Lei Ji, Shubham Garg, Erica N Lamkin, Yuqi Li, Peng Zhao, Sang-Seop Lee
{"title":"July 2026 issue first authors.","authors":"Ren-Lei Ji, Shubham Garg, Erica N Lamkin, Yuqi Li, Peng Zhao, Sang-Seop Lee","doi":"10.1016/j.tips.2026.06.001","DOIUrl":"https://doi.org/10.1016/j.tips.2026.06.001","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284467","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
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