European journal of pharmacology最新文献

{"title":"The next frontier in multiple sclerosis therapies: Current advances and evolving targets","authors":"K. Trideva Sastri ,&nbsp;N. Vishal Gupta ,&nbsp;Anbarasu Kannan ,&nbsp;Suman Dutta ,&nbsp;Riyaz Ali M Osmani ,&nbsp;Balamuralidhara V ,&nbsp;A. Ramkishan ,&nbsp;Shanmuganathan S","doi":"10.1016/j.ejphar.2024.177080","DOIUrl":"10.1016/j.ejphar.2024.177080","url":null,"abstract":"<div><div>Recent advancements in research have significantly enhanced our comprehension of the intricate immune components that contribute to multiple sclerosis (MS) pathogenesis. By conducting an in-depth analysis of complex molecular interactions involved in the immunological cascade of the disease, researchers have successfully identified novel therapeutic targets, leading to the development of innovative therapies. Leveraging pioneering technologies in proteomics, genomics, and the assessment of environmental factors has expedited our understanding of the vulnerability and impact of these factors on the progression of MS. Furthermore, these advances have facilitated the detection of significant biomarkers for evaluating disease activity. By integrating these findings, researchers can design novel molecules to identify new targets, paving the way for improved treatments and enhanced patient care. Our review presents recent discoveries regarding the pathogenesis of MS, highlights their genetic implications, and proposes an insightful approach for engaging with newer therapeutic targets in effectively managing this debilitating condition.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177080"},"PeriodicalIF":4.2,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568049","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}

{"title":"Demyelination in cuprizone mice is ameliorated by calycosin mediated through astrocyte Nrf2 signaling pathway","authors":"Yuxin Chen ,&nbsp;Yuanhua Wang ,&nbsp;Qijin Lu ,&nbsp;Yan Zhao ,&nbsp;Jennifer Cruz ,&nbsp;Jinyun Ma ,&nbsp;Guiqing Ding ,&nbsp;Xi Qiao ,&nbsp;Xiaodong Cheng","doi":"10.1016/j.ejphar.2024.177090","DOIUrl":"10.1016/j.ejphar.2024.177090","url":null,"abstract":"<div><div>Oxidative stress plays a pivotal role in multiple sclerosis (MS), triggering demyelination predominantly through excessive peroxide production and the depletion of antioxidants. The accumulation of oxidative damage can be caused by dysregulation of astrocytes, which are the brain's main regulators of oxidative homeostasis. Calycosin, an essential bioactive component extracted from Astragalus, is recognized for its neuroprotective properties. Although recent research has highlighted calycosin's neuroprotective capabilities, its role in demyelinating conditions like MS remains unclear. In this work, we examined the possible molecular mechanism of calycosin's neuroprotective effect on cuprizone (CPZ)-induced demylination in mice. According to our research, calycosin successfully reduced demyelination and behavioral dysfuction in CPZ mice. Calycosin also decreased the production of oxidative stress and enhanced the expression of antioxidants in CPZ mice and in astrocytes induced by hydrogen peroxide (H₂O₂). Furthermore, both <em>in vivo</em> and <em>in vitro</em> experiments demonstrated that calycosin promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) along with the upregulation of heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and superoxide dismutase (SOD). Importantly, the application of all-trans retinoic acid (ATRA), a specific inhibitor of Nrf2, effectively reversed the myelin-protective and antioxidant effects conferred by calycosin. This study suggested that calycosin might exert neuroprotection by inhibiting oxidative stress and reducing demyelination via the activation of astrocyte Nrf2 signaling. These findings indicated that calycosin might be a potential candidate for treating MS.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177090"},"PeriodicalIF":4.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568021","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}

{"title":"Novel apocynin regulates TRPV1 activity in the trigeminal system and controls pain in a temporomandibular joint neurogenic model","authors":"Taisa Maria Mendes Matuiama Machado ,&nbsp;Iara Gonçalves Aquino ,&nbsp;Marcelo Franchin ,&nbsp;Miguel O. Zarraga ,&nbsp;Daniel Bustos ,&nbsp;Fernanda Papa Spada ,&nbsp;Marcelo Henrique Napimoga ,&nbsp;Juliana Trindade Clemente-Napimoga ,&nbsp;Severino Matias Alencar ,&nbsp;Bruna Benso ,&nbsp;Henrique Ballassini Abdalla","doi":"10.1016/j.ejphar.2024.177093","DOIUrl":"10.1016/j.ejphar.2024.177093","url":null,"abstract":"<div><h3>Objective</h3><div>Herein, we investigate the potential analgesic effect of a newly synthesized chalcone-derived apocynin in a neurogenic pain model.</div></div><div><h3>Methods</h3><div>Molecular docking was used to foretell the apocynin binding features and dynamics with the TRPV1 channel, and the activity was tested <em>in vitro</em>, using transfected HEK 293T cells with the rat TRPV1 receptor. The analgesic effect of apocynin was investigated using a capsaicin-induced pain model. The expression of TRPV1, TRPA1, TRPM8, and MAPKs was assessed by electrophoresis, and immunosorbent assays were performed to quantify the neurotransmitters Substance P, Glutamate, and CGRP. A survival assay using <em>Galleria mellonella</em> was carried out to determine the toxicity.</div></div><div><h3>Results</h3><div>We observed that apocynin exhibits greater thermodynamic stability. Upon apocynin ligand binding, it changes the electrostatic potential for a predominantly electronegative state in the interior and neutral in its external vanilloid pocket. Treatment of apocynin induces antinociceptive effects against the noxious challenge of capsaicin. Histologically, apocynin decreased the number of TRPV1⁺ immunopositive cells. Electrophoresis showed reduced phosphorylation of p44/42 (ERK1/2) and decreased protein levels of substance P, and CGRP. In the survival assay, apocynin showed low toxicity.</div></div><div><h3>Conclusions</h3><div>In conclusion, we provide proof-of-principles that the newly synthesized apocynin compound effectively prevented nociception in a neurogenic model of orofacial pain.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177093"},"PeriodicalIF":4.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568043","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}

{"title":"Cordycepin enhances the Anticancer efficacy of PD-L1 blockade by modulating the tumor microenvironment of colon cancer","authors":"Chen Feng ,&nbsp;Rongzhang Chen ,&nbsp;Xinran Gao ,&nbsp;Weiwei Fang ,&nbsp;Shaoxian Wu ,&nbsp;Lujun Chen ,&nbsp;Xiao Zheng ,&nbsp;Xinyue Ji ,&nbsp;Maoling Yuan ,&nbsp;Yuanyuan Fu ,&nbsp;Hanjie Ying ,&nbsp;Tao Shen ,&nbsp;Dawei Zhu ,&nbsp;Jingting Jiang","doi":"10.1016/j.ejphar.2024.177089","DOIUrl":"10.1016/j.ejphar.2024.177089","url":null,"abstract":"<div><h3>Background</h3><div>PD-L1 blockade has been found to be effective in treating multiple malignancies. Combined therapy is proposed to provide better therapeutic effects. Cordycepin, a prominent bioactive compound found in cordyceps, can inhibit the development of various cancers.</div></div><div><h3>Purpose</h3><div>This study aimed to determine the efficacy of combined anti-PD-L1 antibody and cordycepin in tumor treatment.</div></div><div><h3>Methods</h3><div>A single-cell RNA sequencing was used to analyze the mechanism of combined treatment.</div></div><div><h3>Results</h3><div>Combination therapy of anti-PD-L1 and cordycepin significantly inhibited tumor growth by regulating the T cell ratio and improving the function of CD8⁺T cells. Furthermore, cordycepin promoted the reprogramming of type-II macrophages into type-I macrophages, a process confirmed through flow cytometry analysis of the underlying mechanism.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that the combination of anti-PD-L1 and cordycepin effectively suppressed tumor growth by regulating the proportion of T cells and reprograming type-II macrophages.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177089"},"PeriodicalIF":4.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567990","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}

{"title":"GPR55 antagonist CID16020046 suppresses DNCB-induced atopic dermatitis-like symptoms by suppressing Th1/Th2/Th17 populations in mice","authors":"So-Eun Son ,&nbsp;Dong-Soon Im","doi":"10.1016/j.ejphar.2024.177088","DOIUrl":"10.1016/j.ejphar.2024.177088","url":null,"abstract":"<div><div>G protein-coupled receptor 55 (GPR55) is a lipid-sensing receptor that plays a role as an immune mediator and is primarily upregulated during immune cell activation. There is a lack of knowledge about the role of GPR55 in allergic inflammatory diseases such as atopic dermatitis. The purpose of this study was to investigate the role of GPR55 through the use of its antagonist, CID16020046, in an atopic dermatitis mouse model. It was found that BALB/c mice develop lesions similar to those associated with atopic dermatitis following sensitization and repeated exposure to 1-chloro-2,4-dinitrobenzene (DNCB). It was found that CID16020046 (1 mg/kg, i. p.) alleviated the atopic dermatitis-like symptoms as well as immune dysregulation caused by DNCB. Based on histopathological analysis, CID16020046 reduced ear thickening and mast cell counts in the dermis. CID16020046 decreased DNCB-induced increases in serum IgE levels, as measured using enzyme-linked immunosorbent assays. A significant reduction in lymph node hypertrophy was also observed with CID16020046 as well as significant reductions in CD4⁺ T helper 1 (Th1), Th2, and Th17 cells in the lymph nodes. As a result of the administration of CID16020046, cytokines of Th1 (IFN-γ), Th2 (IL-4 and IL-13), and Th17 (IL-17 A) types were also reduced in the skin and lymph nodes. In conclusion, blocking GPR55 alleviates DNCB-induced atopic dermatitis-like symptoms, suggesting that GPR55 is a potential therapeutic target for allergic inflammatory diseases via immunoregulation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177088"},"PeriodicalIF":4.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564146","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}

{"title":"miR-421-mediated suppression of FGF13 as a novel mechanism ameliorates cardiac hypertrophy by inhibiting endoplasmic reticulum stress","authors":"Yaxin Zhi ,&nbsp;Yanru Duan ,&nbsp;Ying Zhang ,&nbsp;Haijuan Hu ,&nbsp;Fengli Hu ,&nbsp;Pengfei Wang ,&nbsp;Bin Liu ,&nbsp;Chuan Wang ,&nbsp;Demin Liu ,&nbsp;Guoqiang Gu","doi":"10.1016/j.ejphar.2024.177085","DOIUrl":"10.1016/j.ejphar.2024.177085","url":null,"abstract":"<div><div>Pathological cardiac hypertrophy is an independent risk factor for heart failure. Currently, clinical treatments offer limited effectiveness, and both mortality and morbidity from cardiac hypertrophy and heart failure continue to be significant. Therefore, it is extremely urgent to find new intervention targets to prevent and alleviate pathological cardiac hypertrophy. In this study, we explored FGF13 expression and its upstream regulators in hypertrophic hearts. Firstly, we observed an increase in FGF13 expression levels in human hypertrophic myocardium tissues, as well as in mouse models of TAC-induced hypertrophy and in neonatal rat cardiomyocyte (NRCM) models induced by isoproterenol (ISO). Moreover, these elevated levels of FGF13 were shown to positively correlate with hypertrophic markers, including ANP and BNP. By using both gain-of-function and loss-of-function approaches in an in vitro hypertrophy model, we demonstrated that FGF13 knockdown could inhibit endoplasmic reticulum stress (ERS), thereby ameliorating cardiomyocyte hypertrophy. Meanwhile, we investigated the upstream regulators of FGF13 in hypertrophic hearts, and a dual-luciferase reporter assay confirmed that FGF13 is a direct target of miR-421. Overexpression of miR-421 decreased the protein level of FGF13 and ameliorated ISO-induced cardiomyocyte hypertrophy via modulating ER stress. In contrast, overexpression of FGF13 attenuated the ameliorative effect of miR-421 on ISO-induced cardiomyocyte hypertrophy. Taken together, the present results suggested that miR-421 ameliorated ISO-induced cardiomyocyte hypertrophy by negatively regulating FGF13 expression. This finding may offer a novel approach for the treatment of cardiac hypertrophy.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177085"},"PeriodicalIF":4.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564091","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}

{"title":"H2S protects rat cerebral ischemia-reperfusion injury by inhibiting expression and activation of hippocampal ROCK2 at the Thr436 and Ser575 sites","authors":"Fang Fang ,&nbsp;Yi-Ning Guan ,&nbsp;Mei-Jing Zhong ,&nbsp;Ji-Yue Wen ,&nbsp;Zhi-Wu Chen","doi":"10.1016/j.ejphar.2024.177079","DOIUrl":"10.1016/j.ejphar.2024.177079","url":null,"abstract":"<div><h3>Background</h3><div>H₂S is an endogenous gas signal molecule, which protects cerebral ischemia/reperfusion (I/R) injury by phosphorylating rho-associated coiled coil-containing protein kinase 2 (ROCK₂) at Tyr722, and inhibiting ROCK₂ protein expression and activities. We previously reported that H₂S protected rat neurons from hypoxia/reoxygenation injury in vitro through inhibiting phosphorylation of ROCK₂ at Thr436 and Ser575, but it is unclear whether these two sites are involved in protection of H₂S against cerebral I/R injury.</div></div><div><h3>Method</h3><div>Rats transfected with wild-type and mutant eukaryotic plasmids of ROCK₂ in hippocampus were used to establish I/R model by ligating bilateral common carotid artery. Rat behavioral deficit was detected by water maze assay, and ROCK₂, lactate dehydrogenase (LDH), nerve-specific enolase (NSE) and reactive oxygen species (ROS) were determined by ELISA. ROCK₂ expressions was examined by western-blot assay, and bcl-2 and Bax mRNAs were examined by RT-qPCR.</div></div><div><h3>Results</h3><div>NaHS (4.8 mg/kg) significantly inhibited the I/R-increased serum LDH, NSE and ROS in the ROCK₂^wild-pEGFP-N1-transfected rats, but had no obvious effect in the ROCK₂^T436A-pEGFP-N1- or the ROCK₂^S575F-pEGFP-N1-transfected rats; inhibitions of NaHS on the I/R-increased escape latency and the I/R-decreased percentage of target quadrant distance to total distance were markedly attenuated or abolished in the ROCK₂^T436A-pEGFP-N1- or the ROCK₂^S575F-pEGFP-N1-transfected rats compared with those in the ROCK₂^wild-pEGFP-N1-transfected rats; NaHS obviously inhibited the I/R-increased hippocampal ROCK₂ and GFP-ROCK₂ proteins, Bax mRNA, and ROCK₂ activity, as well as the I/R-decreased hippocampal bcl-2 mRNA in the hippocampus of the ROCK₂^wild-pEGFP-N1-transfected rats, but had no significant effect in the ROCK₂^T436A-pEGFP-N1- or the ROCK₂^S575F-pEGFP-N1-transfected rats.</div></div><div><h3>Conclusion</h3><div>H₂S protects cerebral I/R injury in rats by inhibiting expression and activation of hippocampal ROCK₂ via the Thr436 and Ser575 sites.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177079"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564090","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}

{"title":"Targeting HER2 in breast cancer with brain metastases: A pharmacological point of view with special focus on the permeability of blood-brain barrier to targeted treatments","authors":"Giorgio Guglielmi ,&nbsp;Claudio Zamagni ,&nbsp;Marzia Del Re ,&nbsp;Romano Danesi ,&nbsp;Stefano Fogli","doi":"10.1016/j.ejphar.2024.177076","DOIUrl":"10.1016/j.ejphar.2024.177076","url":null,"abstract":"<div><div>Understanding the capability of a drug to penetrate the blood-brain barrier (BBB) is an unmet medical need in patients with positive human epidermal growth factor receptor 2 (HER2 positive) and brain metastases. The National Comprehensive Cancer Network (NCCN) guidelines recommend the use of tyrosine kinase inhibitors (TKIs) lapatinib, neratinib, and tucatinib in co-administration with monoclonal antibodies or chemotherapy drugs and the antibody-drug conjugates (ADCs) trastuzumab-deruxtecan and trastuzumab-emtansine. Predicting the BBB permeability of these therapeutic agents is a pharmacological challenge due to the various factors involved in the barrier functions. In this review article, we discuss about the molecular and cellular features of the barriers located in the central nervous system and the pharmacological parameters found to be important in predicting BBB permeability in human normal brain, and in the presence of brain metastases. Finally, we reported the clinical outcomes and intracranial response of patients with HER2-positive breast cancer with brain metastases treated with targeted TKIs and ADCs.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177076"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564093","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}

{"title":"Integrated metabolomics and network pharmacology analysis to reveal the protective effect of Complanatoside A on nonalcoholic fatty liver disease","authors":"Sijia Jiang ,&nbsp;Xiaoxu Fan ,&nbsp;Jian Hua ,&nbsp;Shuangqiao Liu ,&nbsp;Yingtong Feng ,&nbsp;Danyue Shao ,&nbsp;Yiwei Shen ,&nbsp;Zhen Wang ,&nbsp;Xuehua Yan ,&nbsp;Jingxia Wang","doi":"10.1016/j.ejphar.2024.177074","DOIUrl":"10.1016/j.ejphar.2024.177074","url":null,"abstract":"<div><h3>Introduction</h3><div>The rising prevalence and severe consequences of nonalcoholic fatty liver disease (NAFLD) have driven the quest for preventive medications. Complanatoside A (CA) is the marked flavonoid of Astragali complanati semen, a traditional Chinese herb that acts on the liver meridian and is widely used to treat liver problems. CA has been proven to have considerable lipid-lowering and liver-protective effects in vitro. However, the efficacy of CA in preventing NAFLD has yet to be shown in vivo.</div></div><div><h3>Methods</h3><div>First, the effectiveness of CA against NAFLD was assessed using a high-fat diet (HFD) mouse model. Second, the CA protective mechanism against NAFLD was investigated using a combined metabolomics and network pharmacology strategy. Differential metabolites were identified by metabolomics-based analyses, and metabolic pathway analysis was accomplished by MetaboAnalyst. Potential therapeutic targets were obtained through network pharmacology. Finally, key targets were identified via compound–target networks and validated by molecular docking and western blotting.</div></div><div><h3>Results</h3><div>CA prevented NAFLD mainly by reducing liver lipid accumulation in HFD mice. Metabolomics identified 22 potential biomarkers for CA treatment of NAFLD, primarily involving glycerophospholipid and arachidonic acid metabolism. Fifty-one potential targets were determined by network pharmacology. Co-analysis revealed that albumin, peroxisome proliferator-activated receptor-alpha, retinoid X receptor alpha, interleukin-6, and tumor necrosis factor alpha were key targets.</div></div><div><h3>Conclusion</h3><div>This experiment revealed that CA has a preventive effect on NAFLD, primarily by regulating the peroxisome proliferator-activated receptor-alpha/retinoid X receptor alpha pathway. <span>Furthermore</span>, it provides evidence supporting the potential use of <span>CA</span> in the long-term prevention of NAFLD.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177074"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557403","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}

{"title":"RNAi in psoriasis: A melodic exploration of miRNA, shRNA, and amiRNA with a spotlight on siRNA","authors":"Japneet Singh Purewal,&nbsp;Gaurav Mahesh Doshi","doi":"10.1016/j.ejphar.2024.177083","DOIUrl":"10.1016/j.ejphar.2024.177083","url":null,"abstract":"<div><div>Psoriasis (Pso) is an autoimmune inflammatory skin disease characterised by well-demarcated, red plaques covered in silver scales. It affects people of all ages and can be passed down through generations. Genetics play an important role in determining vulnerability to develop Pso. Several large-scale genome-wide association studies have identified over 80 genetic loci associated with Pso susceptibility. Gene expression can be regulated via RNA interference (RNAi). RNAi suppresses gene expression by degrading mRNA molecules. Since its discovery, RNAi has generated considerable excitement over its potential therapeutic benefits. RNAi is mediated by endogenous small RNA molecules like microRNA (miRNA) or exogenous small RNA molecules like small interfering RNA (siRNA), short hairpin RNA (shRNA), and artificial micro RNA (amiRNA). These small RNA molecules can silence a disease-related gene in a sequence-specific manner. Targeting RNAi pathways can help modify disease-related biological processes in various medical conditions, including autoimmune disorders. In Pso, RNAi can downregulate the expression of molecules involved in the pathophysiology of the disease. Significant progress has been made in the field of RNAi therapeutics. However, further research is needed to fine-tune the design and delivery of RNAi therapeutics in humans. In this review, we discuss various effectors of RNAi, some challenges related to RNAi therapeutics (emphasizing siRNA) and strategies to overcome these challenges. Furthermore, we have discussed some studies that employ RNAi therapeutics for Pso.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177083"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557404","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}