Pharmacological research最新文献

{"title":"Corrigendum to \"The host cell factor DDX3 mediates sex dimorphism in the IFNα response of plasmacytoid dendritic cells upon TLR activation\" [Pharmacol. Res. 216(June) (2025) 107764].","authors":"Sebastian Schloer, Jana Hennesen, Lena Rueschpler, Mohamed Zamzamy, Felix Flomm, Nikolaos-Taxiarchis Skenteris, Wing Hang Ip, Andrea Pirosu, Thomas Dobner, Marcus Altfeld","doi":"10.1016/j.phrs.2025.107899","DOIUrl":"https://doi.org/10.1016/j.phrs.2025.107899","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"107899"},"PeriodicalIF":10.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768931","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}

{"title":"Nuclear Receptors CAR and PXR as Cardiometabolic Regulators.","authors":"Janne Hukkanen, Jenni Küblbeck, Jukka Hakkola, Jaana Rysä","doi":"10.1016/j.phrs.2025.107892","DOIUrl":"https://doi.org/10.1016/j.phrs.2025.107892","url":null,"abstract":"<p><p>The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) were initially described as xenobiotic sensors, but an increasing number of studies have linked their activity to other important physiological processes including glucose and lipid metabolism, implying an expanded role as metabolic sensors. CAR and PXR are nuclear receptors, which share similarities in expression, ligand-specificity, and mechanism of transcriptional regulation but they have their distinct features as well. Together, they regulate a wide array of target genes, whose functions range from elimination of xenobiotics to energy metabolism. Both CAR and PXR have large ligand binding pockets, and especially the PXR pocket is flexible for structurally different chemicals. Consequently, CAR and PXR could have a role in mediating the harmful metabolic effects of drugs and environmental chemicals. Current knowledge supports a role for PXR in the regulation of lipid and cholesterol metabolism. The actions seem to be mostly unfavorable, since the activation of PXR has been shown to promote hepatic lipogenesis and hyperlipidemia, increase plasma cholesterol and impair hepatic LDL uptake. PXR and PXR-regulated circulating 4β-hydroxycholesterol may also influence blood pressure regulation. CAR, in contrast, tends to exert beneficial effects on lipid and glucose homeostasis, since CAR activation has been shown to reduce serum triglyceride and cholesterol levels and have anti-atherogenic properties. Here we review current knowledge on CAR and PXR as regulators of cardiometabolic functions, including glucose and lipid homeostasis, blood pressure regulation and atherosclerosis.</p>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"107892"},"PeriodicalIF":10.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768933","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}

{"title":"Effect of ketamine and esketamine on RNA expression and its relevance for depression: a systematic review.","authors":"Claudia Pisanu, Rosana Carvalho Silva, Mattia Meattini, Massimo Gennarelli, Bernhard T Baune, Alessio Squassina, Alessandra Minelli","doi":"10.1016/j.phrs.2025.107894","DOIUrl":"https://doi.org/10.1016/j.phrs.2025.107894","url":null,"abstract":"<p><p>Treatment-resistant depression (TRD) remains a challenge in psychiatry, necessitating novel therapeutic strategies beyond traditional monoaminergic antidepressants. Ketamine and its S-enantiomer esketamine have demonstrated rapid and robust antidepressant effects in TRD, probably through mechanisms involving glutamatergic modulation, neuroplasticity, and anti-inflammatory properties. However, the molecular underpinnings of these effects are not yet understood. This systematic review aimed to synthesize evidence from human and in vitro studies evaluating transcriptional changes associated with ketamine and esketamine treatment, to identify potential biomarkers and clarify molecular pathways relevant to their antidepressant properties. A systematic search conducted on PubMed and Scopus identified 12 studies assessing RNA expression following ketamine or esketamine treatment in patients with unipolar or bipolar depression or in human-derived cell models. Eligibility and quality were evaluated using PRISMA guidelines and a modified version of Downs and Black checklist. Twelve studies met inclusion criteria, only one of which explored the effect of esketamine, while all others focused on racemic ketamine. Five studies examined peripheral blood gene expression in patients with TRD, while seven assessed mRNA changes in vitro using human-derived cells. Transcriptome and candidate gene expression studies revealed modulation of genes and pathways related to glutamatergic signaling (GRM2, GRIN2D), immune regulation (STAT3, CCL22, IL6), and neuroplasticity (IGF2). No consistent peripheral biomarkers emerged, but transcriptional profiling revealed dynamic molecular responses to ketamine and esketamine. Ketamine and esketamine induce diverse transcriptional changes implicating neuroplastic, inflammatory, and metabolic pathways. Transcriptomic profiling offers a promising approach for uncovering biomarkers and mechanisms of antidepressant response, warranting further multi-omics, large-scale studies.</p>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"107894"},"PeriodicalIF":10.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768932","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}

{"title":"Extracellular Vesicles: A New Frontier in Deciphering the Mechanisms of Traditional Chinese Medicine.","authors":"Kai Wang, ShuangShuang He, YuanRong Wang, ShanShan Guo, Fang Zhang, YuQi Wang, WenQing Dong, Lan Zhang, XiTing Wang, Yu Li","doi":"10.1016/j.phrs.2025.107890","DOIUrl":"https://doi.org/10.1016/j.phrs.2025.107890","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles that mediate intercellular communication and hold significant promise as therapeutic agents, drug delivery vehicles, and biomarkers. This review systematically explores the bidirectional interplay between EVs and Traditional Chinese Medicine (TCM). We first summarize the unique bioactivity and therapeutic potential of Chinese herbal medicine-derived EVs (CHM-EVs), which retain plant-specific components and demonstrate anti-inflammatory, antioxidant, and tissue-protective effects. We critically expand the scope beyond the prevailing discourse on EVs' intrinsic mechanisms to investigate two significant emerging paradigms We examine EVs as innovative delivery platforms for TCM bioactive compounds, demonstrating how EVs enhance solubility, stability, and targeted delivery of challenging components to amplify therapeutic efficacy. Concurrently, we explore how TCM itself modulates endogenous EVs. Active ingredients within TCM formulations exert therapeutic effects by regulating host EV biogenesis, secretion, cargo composition, and bioactivity, as evidenced in diseases ranging from nephropathy to inflammation. We further evaluate challenges in CHM-EVs standardization (isolation, characterization, nomenclature), biosafety, and clinical translation. By integrating these perspectives, this review provides a panoramic overview of how EVs bridge TCM theory with modern mechanistic research, offering innovative strategies for advancing TCM modernization and EV-based therapeutics.</p>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"107890"},"PeriodicalIF":10.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765158","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}

{"title":"New Insights into the Oral Microbiota and Host Epigenetic changes in Obsessive Compulsive Disorder and Major Depressive Disorder: focus on BDNF.","authors":"Antonio Girella, Matteo Vismara, Kenneth J O'Riordan, Eoin Gunnigle, Francesca Mercante, Nicolaja Girone, Mariangela Pucci, Valentina Gatta, Fani Konstantinidou, Liborio Stuppia, John F Cryan, Bernardo Dell'Osso, Claudio D'Addario","doi":"10.1016/j.phrs.2025.107891","DOIUrl":"https://doi.org/10.1016/j.phrs.2025.107891","url":null,"abstract":"<p><p>Obsessive-Compulsive Disorder (OCD) and Major Depressive Disorder (MDD) frequently co-occur, with depressive symptoms affecting OCD progression and vice versa. Identifying biomarkers is crucial for improving diagnosis and treatment. While the gut microbiota's role in psychiatric disorders is well-studied, this research focuses on alterations in the oral microbiota and their relationship with BDNF (Brain-Derived Neurotrophic Factor) DNA methylation in OCD and MDD patients compared to healthy controls. Our findings reveal significant changes in microbiota composition with OCD patients showing increased Actinobacteriota and Firmicutes abundances (p < 0.05; CTRL = n.24, OCD = n.29), while MDD patients exhibiting increased Actinobacteriota and Firmicutes, with reduced Bacteroidota and Proteobacteria abundances (p < 0.05; CTRL = n.24, MDD = n.20). These alterations, including potential post-streptococcal autoimmunity, highlight the microbiota's role in OCD and MDD pathophysiology. Selective changes in BDNF DNA methylation were observed in both disorders at CpG sites in exon I and IV, significantly reduced in OCD and MDD (p < 0.05; CTRL = n.24, OCD = n.29, MDD = n.20) and, following miRNome analysis, showed altered expression of BDNF-targeting microRNAs, with miR-16-5p and miR-29a-3p upregulated in OCD (p < 0.05; CTRL = n.24, OCD = n.17), and miR-29a-3p upregulated and miR-191-5p downregulated in MDD (p < 0.05; CTRL = n.24, MDD = n.16). These findings suggest disorder-specific microbiota and epigenetic profiles, positioning saliva as a non-invasive tool for biomarker identification. This research advances the understanding of microbial-epigenetic interactions in OCD and MDD, potentially guiding early diagnosis and targeted therapies.</p>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"107891"},"PeriodicalIF":10.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765159","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}

{"title":"Novel risk assessment strategy of co-exposure of arsenic and cadmium in seaweeds based on in vivo-in vitro correlation, bio-transformation and speciation.","authors":"Yuan-Sheng Guo, Tian-Tian Zuo, Hong-Yu Jin, Jing Liu, Xian-Long Cheng, Ping Li, Xiao-Dong Li, Liu-Chao Zhu, Feng Wei","doi":"10.1016/j.phrs.2025.107886","DOIUrl":"https://doi.org/10.1016/j.phrs.2025.107886","url":null,"abstract":"<p><p>In recent years, global consumption of seaweed has been on the rise, yet there is a lack of accurate methods for assessing the health risks associated with its consumption. This gap could pose a threat to public safety or lead to wasted resources by government regulatory bodies. In this study, animal models and an innovative PBET (IPBET) were used to determine the bioavailability and bioaccessibility of arsenic (As) and cadmium (Cd) in various seaweeds, followed by an in vivo-in vitro correlation (IVIVC) analysis. The results indicated that the bioaccessibility of As and Cd was strongly correlated with As-RBA and Cd-RBA, highlighting the method's significant potential for predicting As-RBA and Cd-RBA in seaweeds. Additionally, the study explored the impact of mineral elements on the bioaccessibility of As and Cd in seaweed, finding a significant influence. In vivo metabolism experiments in mice revealed that different As species undergo several biochemical transformations in the body, including oxidation, reduction, methylation, and demethylation, all of which should not be overlooked. Building on previous studies, we have developed a new perspective for risk assessment of combined As and Cd exposure in seaweed. Calculations of the target hazard quotient (THQ) and total risk (TR) indicated that factoring in the bioavailability of heavy metals, As species, and biotransformation rates (BR) substantially reduces the health risks associated with seaweed consumption. However, for populations consuming seaweed over the long term, there still remains a certain level of risk to human health.</p>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"107886"},"PeriodicalIF":10.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760676","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}

{"title":"Beyond the surface: P2Y receptor downstream pathways, TLR crosstalk and therapeutic implications for infection and autoimmunity","authors":"Lena Rueschpler ,&nbsp;Sebastian Schloer","doi":"10.1016/j.phrs.2025.107884","DOIUrl":"10.1016/j.phrs.2025.107884","url":null,"abstract":"<div><div>A successful immune response must effectively obtain pathogen clearance upon infection while preventing excessive collateral tissue damage. It is therefore essential to achieve a nuanced fine regulation of pro- and anti-inflammatory signals to orchestrate the optimal immune function and restore homeostatic conditions. In this process, the purinergic system plays the dual role of promoting host antimicrobial effector mechanisms while simultaneously limiting the immune response to the site and duration of infection. This double-edged nature of the purinergic system can also be observed in the modulation of autoimmune conditions. This review aims to provide a thorough overview of P2Y receptor downstream signalling and, for the first time, to illustrate the current state of knowledge on the incompletely understood crosstalk of P2Y receptors with Toll-like receptor (TLR) and inflammasome activation respectively. Additionally, it evaluates the therapeutic potential of targeting P2Y receptors in the context of inflammatory diseases. Recent pre-clinical and clinical studies of P2Y receptors are being presented and put into perspective by highlighting the importance of biased signalling and novel pharmacological strategies.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"219 ","pages":"Article 107884"},"PeriodicalIF":10.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739206","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}

{"title":"Sex/gender differences in clinical pharmacology: A perspective from the IUPHAR World Smart Medication Day 2025.","authors":"M I Lucena, P Galappatthy, K Allegaert, Y Böttiger, N A Buckley, B Medhi, M J Rieder, C Waitt, S N Hilmer","doi":"10.1016/j.phrs.2025.107889","DOIUrl":"10.1016/j.phrs.2025.107889","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"107889"},"PeriodicalIF":10.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754019","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}

{"title":"Primary Cilia as Mechanosensors in Musculoskeletal Homeostasis and Disease.","authors":"Huibo Ti, Zhenyu Zhang, Xielin Yan, Haiting Hu, Keyue Zhang, Shuwen Shi, Junjie Wu, Hao Nie, Zhengdong Yuan, Yuechun Chen, Yifei Fu, Ming-Dong Zhao, Feng-Lai Yuan, Xia Li","doi":"10.1016/j.phrs.2025.107887","DOIUrl":"https://doi.org/10.1016/j.phrs.2025.107887","url":null,"abstract":"<p><p>The musculoskeletal system relies on precise mechanical signal transduction to maintain physiological homeostasis, yet the underlying mechanisms remain incompletely characterized. Primary cilia (PC), membrane-bound organelles that protrude into the extracellular matrix, acting as cellular sensors to integrate biomechanical forces into cellular responses. Moreover, their dynamic assembly and disassembly are tightly coupled to mechanical stress perception, which also suggests a pivotal role in regulating musculoskeletal tissue function. This review systematically synthesizes current evidence on PC-mediated mechanical signaling pathways in bone, muscle, cartilage health, intervertebral disc homeostasis, and tendon matrix crosslinking, elucidating how these structures influence tissue maintenance and repair. We explore the dynamic assembly and disassembly of PC in response to mechanical forces and their impact on downstream signaling pathways. We explore the assembly and disassembly process of PC in response to mechanical forces and their impact on downstream signaling pathways. By identifying key regulatory targets, we discuss the potential regulatory targets of PC for therapeutic interventions in musculoskeletal disorders, offering new perspectives for disease management in the future.</p>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"107887"},"PeriodicalIF":10.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754018","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}

{"title":"Therapeutical peptides - rapidly developing pharmaceutical landscape.","authors":"Ping Zeng, Sharon Shui Yee Leung","doi":"10.1016/j.phrs.2025.107888","DOIUrl":"https://doi.org/10.1016/j.phrs.2025.107888","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":" ","pages":"107888"},"PeriodicalIF":10.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754020","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}