Pharmacological research最新文献

Organ dysfunction induced by hemorrhagic shock: From mechanisms to therapeutic medicines 失血性休克引起的器官功能障碍：从机制到治疗药物

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-05-01 DOI: 10.1016/j.phrs.2025.107755

Qingxia Huang , Yisa Wang , Zepeng Zhang , Mingxia Wu , Jiaqi Liu , Jinjin Chen , Jing Li , Yao Yao , Chen Guo , Daqing Zhao , Wenxiu Qi , Xiangyan Li

{"title":"Organ dysfunction induced by hemorrhagic shock: From mechanisms to therapeutic medicines","authors":"Qingxia Huang , Yisa Wang , Zepeng Zhang , Mingxia Wu , Jiaqi Liu , Jinjin Chen , Jing Li , Yao Yao , Chen Guo , Daqing Zhao , Wenxiu Qi , Xiangyan Li","doi":"10.1016/j.phrs.2025.107755","DOIUrl":"10.1016/j.phrs.2025.107755","url":null,"abstract":"<div><div>Hemorrhagic shock (HS) leads to organ dysfunction, which increases the incidence of unfavorable outcomes in patients. However, adjuvant drug therapy for HS has not been widely accepted, and the benefits of vasopressors are generally considered to have insufficient evidence. Energy homeostasis disruption and excessive immune system activation are the main mechanisms underlying HS-induced organ dysfunction. Recent reports on HS animal models and clinical trials have revealed potential drugs that target the immune response, oxidative damage, and energy homeostasis in HS, providing new insights for the treatment of HS-induced organ dysfunction. In this review, we first discuss the pathophysiology of organ dysfunction involved in HS injury and then systematically review potential drugs that regulate immunity, the inflammatory response, oxidative damage, energy homeostasis, and cell death. We also review the available drugs with clinical evidence of HS-induced organ dysfunction efficacy. Treatment strategies combined with an improved understanding of the organ injury mechanisms of HS may help identify and develop targeted therapeutic modalities that mitigate severe organ dysfunction and reduce mortality caused by HS injury.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107755"},"PeriodicalIF":9.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902382","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

MMP3 at the crossroads: Linking molecular pathways to disease diagnosis and therapy 十字路口的MMP3：将分子途径与疾病诊断和治疗联系起来

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-04-30 DOI: 10.1016/j.phrs.2025.107750

Jing Jiang , Qiong Wu , Snekha Rajasekaran , Rongxue Wu

{"title":"MMP3 at the crossroads: Linking molecular pathways to disease diagnosis and therapy","authors":"Jing Jiang , Qiong Wu , Snekha Rajasekaran , Rongxue Wu","doi":"10.1016/j.phrs.2025.107750","DOIUrl":"10.1016/j.phrs.2025.107750","url":null,"abstract":"<div><div>Matrix metalloproteinase 3 (MMP-3) is a multifaceted enzyme that plays a critical role in the regulation of extracellular matrix (ECM) dynamics, influencing both normal physiological and pathological processes. In addition to its established role in ECM degradation, MMP-3 is gaining recognition for modulating cellular behaviors such as inflammation, migration, and proliferation. Recent research has uncovered its capacity to activate latent signaling molecules, release growth factors from the ECM and interact with various cell surface receptors, linking MMP-3 to the progression of various diseases, including inflammatory diseases, infection diseases, cardiovascular diseases, neurodegenerative disorders, and cancer. The review provides an overview of MMP-3’s molecular regulation, emphasizing the mechanisms controlling its expression and activity. We discuss MMP3’s involvement in both ECM-dependent and independent pathways, and its potential as a diagnostic, prognostic biomarker in various diseases. Additionally, we explore therapeutic strategies targeting MMP-3, summarizing ongoing efforts to develop specific inhibitors and modulate its activity in different pathologic conditions. Through this review, we aim to consolidate the diverse functions of MMP-3 and provide new insights into future research directions, particularly in translating these findings into clinical applications.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107750"},"PeriodicalIF":9.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906656","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

Perturbations of CB1 receptor signalling during adolescence impair cortical myelination in female rats 青春期CB1受体信号的扰动损害雌性大鼠皮质髓鞘形成

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-04-29 DOI: 10.1016/j.phrs.2025.107758

Erica Zamberletti , Cristina Manenti , Pamela Prini , Marina Gabaglio , Annalisa Grimaldi , Laura Pulze , Riccardo Grassi , Tiziana Rubino

{"title":"Perturbations of CB1 receptor signalling during adolescence impair cortical myelination in female rats","authors":"Erica Zamberletti , Cristina Manenti , Pamela Prini , Marina Gabaglio , Annalisa Grimaldi , Laura Pulze , Riccardo Grassi , Tiziana Rubino","doi":"10.1016/j.phrs.2025.107758","DOIUrl":"10.1016/j.phrs.2025.107758","url":null,"abstract":"<div><div>The constant increase in cannabis use among adolescents raises concerns about its potential neurobehavioral effects. Adolescence is a critical period for brain development, involving significant changes in grey and white matter. Grey matter decreases as the brain undergoes synaptic pruning, while white matter increases due to myelination. Cannabis use during this developmental window, particularly its active ingredient delta-9-tetrahydrocannabinol (THC), may disrupt these processes, increasing the risk of developing psychiatric disorders later in life. While the impact of THC on grey matter has been explored, the specific role of CB1 receptors as well as the effect of THC exposure in adolescent myelination remain unclear. This study investigates how CB1 receptor blockade and THC exposure during adolescence affect myelination in the prefrontal cortex of female rats. Blocking CB1 receptors during adolescence hindered myelination in the prefrontal cortex. Behaviourally, this disruption in myelin formation was associated with increased risk-taking behaviour. Notably, our data suggest that alterations in the AKT/Hippo/YAP signalling pathway may play a crucial role in mediating these effects. Supporting the involvement of the endocannabinoid system in cortical myelination during adolescence, we found that administering exogenous THC impaired myelin formation only when given during early to mid-adolescence. Moreover, when a more intensive THC exposure protocol was applied during this developmental period, the effects on myelination were long-lasting and persisted into adulthood. Overall, these data support a role for CB1 receptors in shaping cortical myelination in adolescent female rats and show that adolescent exposure to THC might adversely impact this developmental process.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107758"},"PeriodicalIF":9.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886045","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

Calcaratarin D, a labdane diterpenoid, attenuates bleomycin-induced pulmonary fibrosis by blocking Wnt/β-catenin signaling pathway Calcaratarin D，一种labdane二萜，通过阻断Wnt/β-catenin信号通路减轻博莱霉素诱导的肺纤维化

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-04-29 DOI: 10.1016/j.phrs.2025.107756

Wupeng Liao , Yuet Ang , Adrian C.L. Kee , Valencia Lim , Albert Y.H. Lim , Christina L.L. Chai , W.S. Fred Wong

{"title":"Calcaratarin D, a labdane diterpenoid, attenuates bleomycin-induced pulmonary fibrosis by blocking Wnt/β-catenin signaling pathway","authors":"Wupeng Liao , Yuet Ang , Adrian C.L. Kee , Valencia Lim , Albert Y.H. Lim , Christina L.L. Chai , W.S. Fred Wong","doi":"10.1016/j.phrs.2025.107756","DOIUrl":"10.1016/j.phrs.2025.107756","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is one of the most common interstitial lung diseases with a high mortality rate. Calcaratarin D (CalD), a labdane diterpenoid, has been shown to possess anti-inflammatory properties. The present study evaluated the therapeutic potential of CalD in pulmonary fibrosis. A single dose of bleomycin (BLM, 2.5 mg/kg) was instilled intratracheally in mice for up to 21 days to develop lung fibrosis. Oral CalD (50 mg/kg) reduced BLM-induced inflammatory cell infiltration, especially pro-fibrotic Arg1-expressing interstitial macrophages in the bronchoalveolar lavage fluid. During the late fibrotic phase, CalD decreased BLM-induced mortality and body weight loss. In addition, CalD ameliorated lung histopathology, reduced collagen deposition and mucus hypersecretion, and improved lung functions in BLM-exposed mice. Furthermore, CalD modulated the levels of pro-inflammatory cytokines, chemokines, and growth factors in BAL fluid and lung tissues. In mouse lungs, BLM selectively upregulated Wnt10A level and promoted β-catenin nuclear translocation. CalD not only blocked Wnt10A/β-catenin signaling pathway but also reduced pro-fibrotic markers such as collagens, α-SMA and FHL2. In normal human lung fibroblasts, CalD inhibited TGF-β1-stimulated pro-fibrotic markers and Wnt/β-catenin signaling pathway by reducing Wnt10A production, upregulating endogenous Wnt antagonist DKK1 level, dephosphorylating Wnt ligand co-receptor LRP6, and preventing β-catenin and YAP/TAZ nuclear translocation. The antifibrotic action of CalD was shown to be dependent on its α,β-unsaturated γ-butyrolactone structure that is essential for CalD to form covalent interaction with cellular protein targets. Our results imply that CalD could be a novel antifibrotic agent for IPF, acting through blockade of the Wnt/β-catenin signaling pathway.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107756"},"PeriodicalIF":9.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890821","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

Imaging technology in tracking the intravital fate of transplanted stem cells 成像技术在追踪移植干细胞生命命运中的应用

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-04-29 DOI: 10.1016/j.phrs.2025.107752

Liming Shen , Chengze Li , Yulian Li , Xin Guan , Wei Zou , Jing Liu

引用次数: 0

IUPHAR review: Microbiota-gut-brain axis and its role in neuropsychiatric disorders IUPHAR综述：微生物-肠-脑轴及其在神经精神疾病中的作用

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-04-28 DOI: 10.1016/j.phrs.2025.107749

Seung-Hoon Lee , Changsu Han , Cheolmin Shin

{"title":"IUPHAR review: Microbiota-gut-brain axis and its role in neuropsychiatric disorders","authors":"Seung-Hoon Lee , Changsu Han , Cheolmin Shin","doi":"10.1016/j.phrs.2025.107749","DOIUrl":"10.1016/j.phrs.2025.107749","url":null,"abstract":"<div><div>The human gut microbiome, composed of a vast array of microorganisms that have co-evolved with humans, is crucial for the development and function of brain systems. Research has consistently shown bidirectional communication between the gut and the brain through neuronal, endocrine, and immunological, and chemical pathways. Recent neuroscience studies have linked changes in the microbiome and microbial metabolites to various neuropsychiatric disorders such as autism, depression, anxiety, schizophrenia, eating disorders, and neurocognitive disorders. Novel metagenome-wide association studies have confirmed these microbiome variations in large samples and expanded our understanding of the interactions between human genes and the gut microbiome. The causal relationship between gut microbiota and neuropsychiatric disorders is being elucidated through the establishment of large cohort studies incorporating microbiome data and advanced statistical techniques. Ongoing animal and human studies focused on the microbiota-gut-brain axis are promising for developing new prevention and treatment strategies for neuropsychiatric conditions. The scope of these studies has broadened from microbiome-modulating therapies including prebiotics, probiotics, synbiotics and postbiotics to more extensive approaches such as fecal microbiota transplantation. Recent systematic reviews and meta-analyses have strengthened the evidence base for these innovative treatments. Despite extensive research over the past decade, many intriguing aspects still need to be elucidated regarding the role and therapeutic interventions of the microbiota-gut-brain axis in neuropsychiatric disorders.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107749"},"PeriodicalIF":9.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886043","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

Molecular mechanisms of pyroptosis in non-alcoholic steatohepatitis and feasible diagnosis and treatment strategies 非酒精性脂肪性肝炎热亡的分子机制及可行的诊断和治疗策略

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-04-28 DOI: 10.1016/j.phrs.2025.107754

Dong-fang Shang , Wen-qian Xu , Qing Zhao , Chen-lu Zhao , Si-ying Wang , Yong-li Han , He-guo Li , Ming-hao Liu , Wen-xia Zhao

引用次数: 0

Commentary on: “IUPHAR review – Novel therapeutic targets for schizophrenia treatment: A translational perspective” 评论：“IUPHAR综述-精神分裂症治疗的新治疗靶点：翻译视角”

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-04-28 DOI: 10.1016/j.phrs.2025.107757

Mats B. Humble, Daniel Eklund, Susanne Bejerot

引用次数: 0

Curcumin modulates β-catenin stabilization via targeting proteasomal deubiquitinating enzyme USP14☆ 姜黄素通过靶向蛋白酶体去泛素化酶USP14☆调节β-连环蛋白的稳定

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-04-26 DOI: 10.1016/j.phrs.2025.107745

Mengzhen Shen , Lizhe Chen , Jie Jiang, Ziye Wang, Qing Gong, Xue Zhang, Xisong Ke, Yi Qu

{"title":"Curcumin modulates β-catenin stabilization via targeting proteasomal deubiquitinating enzyme USP14☆","authors":"Mengzhen Shen , Lizhe Chen , Jie Jiang, Ziye Wang, Qing Gong, Xue Zhang, Xisong Ke, Yi Qu","doi":"10.1016/j.phrs.2025.107745","DOIUrl":"10.1016/j.phrs.2025.107745","url":null,"abstract":"<div><div>Loss of β-catenin homeostasis is tightly associated with human malignancies, modulation of β-catenin stabilization could be an attractive strategy for cancer therapy. In the present study, we demonstrated that an ancient drug curcumin was associated with selective accumulation of phosphorylated β-catenin (PBC) tagged with both ubiquitin (Ub) and Ub-like (Ubl) protein NEDD8. We further identified USP14, a deubiquitinating enzyme (DUB) in 19S proteasome, as a functional target of curcumin in modulating β-catenin. Curcumin enhances USP14-mediated PBC trapping and modulates proteasome associations, loss of USP14 significantly attenuated curcumin-increased PBC. Additionally, we found that USP14 deficiency suppressed mitotic entry and cell proliferation, targeting USP14 and PBC was essential for curcumin inhibition of cancer. Taken together, our study not only revealed the association of USP14 with PBC degradation within the proteasome, but also provided a unique small molecule curcumin targeting USP14 to modulate β-catenin for cancer therapy.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107745"},"PeriodicalIF":9.1,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894678","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

Elevated activity of plasma dipeptidyl peptidase 4 upon stress can be targeted to reverse tumor immunosuppression 应激时血浆二肽基肽酶4活性升高可靶向逆转肿瘤免疫抑制

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-04-26 DOI: 10.1016/j.phrs.2025.107696

Peipei Li , Menghe Liang , Junlin Zhu , Jian Chen , Lin Xia , Ziqi Jin , Xiao Zhang , Shuqing Zhang , Qi Wang , Zhen Liu , Yu Ping , Zhenxin Wang , Catherine CL Wong , Yi Zhang , Heng Yang , Zilu Ye , Yuting Ma

{"title":"Elevated activity of plasma dipeptidyl peptidase 4 upon stress can be targeted to reverse tumor immunosuppression","authors":"Peipei Li , Menghe Liang , Junlin Zhu , Jian Chen , Lin Xia , Ziqi Jin , Xiao Zhang , Shuqing Zhang , Qi Wang , Zhen Liu , Yu Ping , Zhenxin Wang , Catherine CL Wong , Yi Zhang , Heng Yang , Zilu Ye , Yuting Ma","doi":"10.1016/j.phrs.2025.107696","DOIUrl":"10.1016/j.phrs.2025.107696","url":null,"abstract":"<div><div>The interplay between stress-induced metabolic reprogramming and perturbations in the cancer-immune dialogue is a challenging research topic with huge knowledge gaps to fill. In a repeated social defeat model, we discovered that circulating corticosterone, blood glucose, and plasma DPP4 activity were increased in stressed mice. Consistently, three independent cohort studies showed that plasma DPP4 activity was positively correlated with the severity of psychological distress of newly diagnosed cancer patients. Stress-induced surge of glucocorticoid can boost DPP4 activity via glucocorticoid receptor signaling without influencing <em>Dpp4</em> transcription or the abundance of soluble DPP4. Albeit catalytic inhibition of DPP4 upon stress can’t normalize the behavioral pattern and glucocorticoid secretion, it managed to reverse the expansion of circulating neutrophils and monocytes, restored the efficacy of prophylactic tumor vaccine, and augmented the priming of tumor-antigen specific T cells. DPP4 blockade in the context of stress largely enhanced the intratumoral accumulation of CD8<sup>+</sup>T cells and DCs, cytokine production by CD8<sup>+</sup>T and NK cells in situ, and tumor antigen presentation in vitro. Proteome profiling of mouse plasma revealed stress-related DPP4-sensitive changes that can be linked to immunological alterations and disturbed protease network. Altogether, elevated DPP4 activity may be targeted in cancer patients with psychiatric comorbidities to boost anti-tumor immunity.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"215 ","pages":"Article 107696"},"PeriodicalIF":9.1,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873224","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