European journal of pharmacology最新文献_第6页

Mesenchymal stem cells alleviate inflammatory responses through regulation of T-cell subsets 间充质干细胞通过调节 T 细胞亚群缓解炎症反应

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-09-12 DOI: 10.1016/j.ejphar.2024.176996

{"title":"Mesenchymal stem cells alleviate inflammatory responses through regulation of T-cell subsets","authors":"","doi":"10.1016/j.ejphar.2024.176996","DOIUrl":"10.1016/j.ejphar.2024.176996","url":null,"abstract":"<div><p>Immune-mediated inflammatory disease (IMID) is a complex disorder characterized by excessive immune responses involving T cells and their subsets, leading to direct tissue damage. T cells can be broadly categorized into CD4<sup>+</sup> T cells and CD8<sup>+</sup> T cells. CD4<sup>+</sup> T cells are composed of several subsets, including T helper (Th)1, Th2, Th9, Th17, Th22, follicular helper T cells (Tfhs), and regulatory T cells (Tregs), while effector CD8<sup>+</sup> T cells consist mainly of cytotoxic T cells (CTLs). Current therapies for IMID are ineffective, prompting exploration into mesenchymal stem cells (MSCs) as a promising clinical treatment due to their immunomodulatory effects and self-renewal potential. Recent studies have shown that MSCs can suppress T cells through direct cell-to-cell contact or secretion of soluble cytokines. Nevertheless, the precise effects of MSCs on T cell subsets remain inadequately defined. In this review, we summarize the most recent studies that have examined how MSCs modulate one or more effector T-cell subsets and the mechanisms behind these modifications in vitro and several mouse models of clinical inflammation. This also provides theoretical support and novel insights into the efficacy of clinical treatments involving MSCs. However, the efficacy of MSC therapies in clinical models of inflammation varies, showing effective remission in most cases, but also with exacerbation of T-cell-mediated inflammatory damage in some instances.</p></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Anxiety disorders: Treatments, models, and circuitry mechanisms 焦虑症：治疗、模型和回路机制

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-09-11 DOI: 10.1016/j.ejphar.2024.176994

{"title":"Anxiety disorders: Treatments, models, and circuitry mechanisms","authors":"","doi":"10.1016/j.ejphar.2024.176994","DOIUrl":"10.1016/j.ejphar.2024.176994","url":null,"abstract":"<div><p>Anxiety disorders are one of the most prevalent mental health conditions worldwide, imposing a significant burden on individuals affected by them and society in general. Current research endeavors aim to enhance the effectiveness of existing anxiolytic drugs and reduce their side effects through optimization or the development of new treatments. Several anxiolytic novel drugs have been produced as a result of discovery-focused research. However, many drug candidates that show promise in preclinical rodent model studies fail to offer any substantive clinical benefits to patients. This review provides an overview of the diagnosis and classification of anxiety disorders together with a systematic review of anxiolytic drugs with a focus on their targets, therapeutic applications, and side effects. It also provides a concise overview of the constraints and disadvantages associated with frequently administered anxiolytic drugs. Additionally, the study comprehensively reviews animal models used in anxiety studies and their associated molecular mechanisms, while also summarizing the brain circuitry related to anxiety. In conclusion, this article provides a valuable foundation for future anxiolytic drug discovery efforts.</p></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014299924006848/pdfft?md5=c07435c1d5b4290feeaaa21c2f9c888d&pid=1-s2.0-S0014299924006848-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Anti-inflammatory effects of Gingerenone A through modulation of toll-like receptor signaling pathways 姜酮 A 通过调节收费样受体信号通路发挥抗炎作用

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-09-11 DOI: 10.1016/j.ejphar.2024.176997

引用次数: 0

Sodium butyrate alleviates lipopolysaccharide-induced inflammation through JAK/STAT signalling in primary human corneal fibroblasts 丁酸钠通过 JAK/STAT 信号缓解原代人类角膜成纤维细胞中脂多糖诱导的炎症反应

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-09-11 DOI: 10.1016/j.ejphar.2024.176998

{"title":"Sodium butyrate alleviates lipopolysaccharide-induced inflammation through JAK/STAT signalling in primary human corneal fibroblasts","authors":"","doi":"10.1016/j.ejphar.2024.176998","DOIUrl":"10.1016/j.ejphar.2024.176998","url":null,"abstract":"<div><h3>Background</h3><p>Bacterial keratitis is a common cause of blindness. Antibiotic treatment leads to the rapid release of lipopolysaccharide (LPS), which can activate corneal fibroblasts and cause persistent and excessive inflammatory responses. The anti-inflammatory drugs currently used to treat keratitis have serious side effects. Therefore, the ability of sodium butyrate (NaB), which can suppress the production of proinflammatory cytokines and promote the production of anti-inflammatory cytokines, to ameliorate keratitis was assessed in the present study.</p></div><div><h3>Methods</h3><p>The effect of NaB on the viability of primary human corneal fibroblasts was assayed with a CCK-8 kit. Cell migration was assessed by an in vitro scratch assay. Cell phenotypes were assessed by Western blotting and immunofluorescence staining. An antibody array was used to measure the production of proinflammatory cytokines and chemokines.</p></div><div><h3>Results</h3><p>At 0–1 mM, NaB had no significant effect on cell viability, promoted the expression of the keratocyte marker keratocan and inhibited the fibroblast marker vimentin. Inhibition of cell migration was observed in the wound healing assay. By targeting the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway, NaB decreased the levels of inflammation-related cytokines and chemokines whose expression was induced by LPS.</p></div><div><h3>Conclusions</h3><p>NaB maintained the keratocyte phenotype, inhibited cell migration, and relieved LPS-induced inflammatory responses through the JAK/STAT signalling pathway.</p></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Restoration of ARA metabolic disorders in vascular smooth muscle cells alleviates intimal hyperplasia 恢复血管平滑肌细胞中的 ARA 代谢紊乱可减轻内膜增生

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-09-10 DOI: 10.1016/j.ejphar.2024.176824

{"title":"Restoration of ARA metabolic disorders in vascular smooth muscle cells alleviates intimal hyperplasia","authors":"","doi":"10.1016/j.ejphar.2024.176824","DOIUrl":"10.1016/j.ejphar.2024.176824","url":null,"abstract":"<div><p>Intimal hyperplasia (IH) is an innegligible issue for patients undergoing interventional therapy. The proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor-BB (PDGF-BB) are critical events in the development of IH. While the exact mechanism and effective target for IH needs further investigation. Metabolic disorders of arachidonic acid (ARA) are involved in the occurrence and progression of various diseases. In this study, we found that the expressions of soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) were significantly increased in the VSMCs during balloon injury-induced IH. Then, we employed a COX-2/sEH dual inhibitor PTUPB to increase the concentration of epoxyeicosatrienoic acids (EETs) while prevent the release of pro-inflammatory prostaglandins. Results showed that PTUPB treatment significantly reduced neointimal thickening induced by balloon injury in rats <em>in vivo</em> and inhibited PDGF-BB-induced proliferation and migration of VSMCs <em>in vitro</em>. Our results showed that PTUPB may reverse the phenotypic transition of VSMCs by inhibiting Pttg1 expression. In conclusion, we found that the dysfunction of ARA metabolism in VSMCs contributes to IH, and the COX-2/sEH dual inhibitor PTUPB attenuates IH progression by reversing the phenotypic switch in VSMC through the Sirt1/Pttg1 pathway.</p></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

ENAH transcriptionally activated by YY1 promotes growth and invasion of laryngocarcinoma cells through PI3K/AKT signaling 由 YY1 转录激活的ENAH通过 PI3K/AKT 信号促进喉癌细胞的生长和侵袭

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-09-10 DOI: 10.1016/j.ejphar.2024.176991

{"title":"ENAH transcriptionally activated by YY1 promotes growth and invasion of laryngocarcinoma cells through PI3K/AKT signaling","authors":"","doi":"10.1016/j.ejphar.2024.176991","DOIUrl":"10.1016/j.ejphar.2024.176991","url":null,"abstract":"<div><h3>Background</h3><p>Laryngocarcinoma is a common malignancy in the upper respiratory tract. Enabled homolog (ENAH) is an actin-binding protein that is associated with the development of various cancers. However, its role and mechanism in laryngocarcinoma remain unknown.</p></div><div><h3>Methods</h3><p>The ENAH level in laryngocarcinoma was examined <em>in silico</em>, <em>in vitro</em> and <em>in vivo</em>. The prognostic analysis of the ENAH level was assessed on laryngocarcinoma patients. Gain- and loss-of-function assays were conducted in AMC-HN-8 and TU686 cells. Sh-ENAH-containing AMC-HN-8 cells were implanted into naked mice. The role and mechanism of ENAH in laryngocarcinoma were investigated by CCK-8, transwell, immunofluorescence, dual luciferase, RT-qPCR, immunohistochemistry, and western blotting experiments.</p></div><div><h3>Results</h3><p>The ENAH level was upregulated in laryngocarcinoma, which predicted a poor prognosis in laryngocarcinoma patients. Gain- and loss-of-function results showed that ENAH promoted proliferation, invasion and EMT of laryngocarcinoma cells. Moreover, ENAH was transcriptionally activated by YY1, and YY1/ENAH axis enhanced these malignant progresses of laryngocarcinoma cells. Besides, ENAH activated the PI3K/AKT pathway, and 740Y-P abolished the accelerative role of ENAH in proliferation, invasion and EMT of laryngocarcinoma cells. Furthermore, knockdown of ENAH reduced tumor size and weight, and the expression level of vimentin and PI3K/AKT pathway in tumor-bearing mice.</p></div><div><h3>Conclusion</h3><p>ENAH transcriptionally activated by YY1 promotes cell growth, invasion and EMT of laryngocarcinoma through the activation of PI3K/AKT signaling.</p></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A multi-target ligand (JM-20) prevents morphine-induced hyperalgesia in naïve and neuropathic rats 一种多靶点配体（JM-20）可防止吗啡诱导的新生大鼠和神经病理性大鼠痛觉减退

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-09-10 DOI: 10.1016/j.ejphar.2024.176992

{"title":"A multi-target ligand (JM-20) prevents morphine-induced hyperalgesia in naïve and neuropathic rats","authors":"","doi":"10.1016/j.ejphar.2024.176992","DOIUrl":"10.1016/j.ejphar.2024.176992","url":null,"abstract":"<div><p>The present study examines the possible inhibitory effect of JM-20, a multi-target neuroprotective compound, on the development of morphine-induced hyperalgesia in Male Sprague-Dawley naïve rats. Additionally, the impact of JM-20 on chronic constriction injury (CCI) rats under chronic morphine exposure was investigated, and its efficacy in reducing mechanical hypersensitivity and histopathological changes in the sciatic nerve was assessed. JM-20 (20 mg/kg, <em>per os</em> [p.o.]), administered 60 min before morphine (10 mg/kg, s.c. twice daily at 12 h intervals) for ten days, significantly inhibited the development of morphine-induced hyperalgesia assessed using an electronic pressure-meter paw test, hot-plate, and formalin test, as well as the appearance of spontaneous withdrawal somatic symptoms in rats. Furthermore, JM-20 decreases spinal pro-inflammatory interleukin-1β and restores glutathione to close physiological concentrations, biomarkers directly related to the intensity of mechanical hypernociception. After CCI and sham surgery, co-treatment with JM-20 (10 mg/kg, p.o.) for five days decreased morphine increased-mechanical hypersensitivity, even 12 days after its discontinuation. Continued morphine treatment imposed a neuroinflammatory challenge in CCI animals, further increasing cellularity (>75% immune cell infiltration) with lymphocytes and macrophages. However, JM-20 co-treatment still reduced the presence of cellular infiltrates (51–75%) with a predominance of lymphocytes. Even in the absence of nerve injury, JM-20 attenuated the peripheral neuroinflammatory response observed in morphine-treated sham-operated animals (0% vs. 1–25%). These findings suggest that JM-20 could prevent morphine-induced hyperalgesia by anti-inflammatory and antioxidant mechanisms.</p></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Pervasive expostulation of p53 gene promoting the precipitation of neurogenic convulsions: A journey in therapeutic advancements 促进神经源性惊厥沉淀的 p53 基因普遍表达：治疗进步之旅

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-09-07 DOI: 10.1016/j.ejphar.2024.176990

{"title":"Pervasive expostulation of p53 gene promoting the precipitation of neurogenic convulsions: A journey in therapeutic advancements","authors":"","doi":"10.1016/j.ejphar.2024.176990","DOIUrl":"10.1016/j.ejphar.2024.176990","url":null,"abstract":"<div><p>Epilepsy, a neurological disorder characterized by prolonged and excessive seizures, has been linked to elevated levels of the tumor suppressor gene p53, which contributes to neuronal dysfunction. This review explores the molecular mechanisms of p53 in epilepsy and discusses potential future therapeutic strategies. Research indicates that changes in p53 expression during neuronal apoptosis, neuroinflammation, and oxidative stress play a significant role in the pathogenesis of epilepsy. Elevated p53 disrupts glutamatergic neurotransmission and hyperactivates NMDA and AMPA receptors, leading to increased neuronal calcium influx, mitochondrial oxidative stress, and activation of apoptotic pathways mediated neuronal dysfunction, exacerbating epileptogenesis. The involvement of p53 in epilepsy suggests that targeting this protein could be beneficial in mitigating neuronal damage and preventing seizure recurrence. Pharmacological agents like pifithrin-α have shown promise in reducing p53-mediated apoptosis and seizure severity. Gene therapy approaches, such as viral vector-mediated delivery of wild-type p53 or RNA interference targeting mutant p53, have also been effective in restoring normal p53 function and reducing seizure susceptibility. Despite these advances, the heterogeneous nature of epilepsy and potential long-term side effects of p53 modulation present challenges. Future research should focus on elucidating the precise molecular mechanisms of p53 and developing personalized therapeutic strategies. Modulating p53 activity holds promise for reducing seizure susceptibility and improving the quality of life for individuals with epilepsy. The current review provides the understanding the intricate role of p53 in neuroinflammatory pathways, including JAK-STAT, JNK, NF-κB, Sonic Hedgehog, and Wnt, is crucial for developing targeted therapies.</p></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142163075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A dual αvβ1/αvβ6 integrin inhibitor Bexotegrast (PLN-74809) ameliorates organ injury and fibrogenesis in fibrotic kidney disease αvβ1/αvβ6整合素双重抑制剂Bexotegrast（PLN-74809）可改善纤维化肾病的器官损伤和纤维生成。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-09-06 DOI: 10.1016/j.ejphar.2024.176983

引用次数: 0

Resistance to 5-fluorouracil: The molecular mechanisms of development in colon cancer cells 对 5-氟尿嘧啶的抗药性：结肠癌细胞发展的分子机制。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-09-04 DOI: 10.1016/j.ejphar.2024.176979

{"title":"Resistance to 5-fluorouracil: The molecular mechanisms of development in colon cancer cells","authors":"","doi":"10.1016/j.ejphar.2024.176979","DOIUrl":"10.1016/j.ejphar.2024.176979","url":null,"abstract":"<div><p>Colon cancer is a significant health problem worldwide as it is one of the most common and deadliest cancers. The standard approach for the treatment of colon cancer is 5-fluorouracil (5-FU) based chemotherapy, which is limited by the development of resistance to this drug. Therefore, our study aimed to establish 5-FU resistance in SW-480 and HT-29 colon cancer cells and to precisely determine the molecular mechanisms and biomarkers that contribute to its development, both after short-term exposure and in cells with already developed resistance (SW-480-5FUR and HT-29-5FUR). The expression of various molecules involved in the different mechanisms of resistance development was monitored at the gene (qPCR) and protein (immunocytochemistry) levels. Based on the obtained results, alterations in the 5-FU anabolic pathway, biotransformation, drug efflux, mismatch repair, and apoptosis process together contributed to the development of 5-FU resistance in SW-480 and HT-29 colon cancer cells. In addition, <em>UMPS</em>, <em>ABCC1</em>, <em>ABCC5</em>, and <em>MLH1</em>, as well as the disturbed ratio of pro-apoptotic <em>BAX</em> and anti-apoptotic <em>BCL2</em>, should be taken into consideration as potential targets for the discovery of 5-FU resistance-related biomarkers in colon cancer cells. We suggest that future investigations focus on further validation of these findings by additional <em>in vitro</em> and <em>in vivo</em> testing, which is a limitation of our study.</p></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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