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    Effect of statins on arterial wall inflammation as assessed by 18F-FDG PET CT: an updated systematic review and meta-analysis
    (BMC, 2024) Jamialahmadi, Tannaz; Reiner, Zeljko; Simental-Mendia, Luis E.; Almahmeed, Wael; Karav, Sercan; Eid, Ali H.; Giammarile, Francesco
    BackgroundPathogenesis of atherosclerosis is largely mediated by inflammatory process. Statins are lipid-lowering drugs which also have anti-inflammatory effects. 18 fluorine radiolabeled fluorodeoxyglucose (18 F-FDG) positron emission tomography-computed tomography (PET-CT) is considered to be a good indicator of arterial wall inflammation. Therefore, in this meta-analysis the role of statins on inflammatory process in the artery wall was evaluated using this method since its actual validity for this purpose is not yet well established.MethodsPubMed, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases were searched using MESH terms and keywords. Funnel plot, Begg's rank correlation, and Egger's weighted regression tests evaluated publication bias in the meta-analysis. In cases where funnel plot asymmetry was observed, the trim and fill method was used to check the input of potentially missing studies.ResultsFindings of 10 clinical trials involving 373 subjects showed a remarkable reduction of arterial wall 18 F-FDG uptake according to target-to-background ratio (TBR) index after treatment with statins. Subgroup analysis showed a significant decrease in TBR with high-intensity and non-significant reduction of TBR with low-to-moderate-intensity statin therapy.ConclusionTreatment with statins suppressed arterial wall inflammation as shown by using 18 F-FDG PET-CT.
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    Exploring the antioxidant properties of semaglutide: A comprehensive review
    (Elsevier Science Inc, 2024) Yaribeygi, Habib; Maleki, Mina; Forouzanmehr, Behina; Kesharwani, Prashant; Jamialahmadi, Tannaz; Karav, Sercan; Sahebkar, Amirhossein
    Patients with diabetes commonly experience an aberrant production of free radicals and weakened antioxidative defenses, making them highly susceptible to oxidative stress development. This, in turn, can induce and promote diabetic complications. Therefore, utilizing antidiabetic agents with antioxidative properties can offer dual benefits by addressing hyperglycemia and reducing oxidative damage. Semaglutide, a recently approved oral form of glucagon-like peptide-1 (GLP-1) analogues, has shown potent antidiabetic effects. Additionally, recent studies have suggested that it possesses antioxidative properties. However, the exact effects and the molecular pathways involved are not well understood. In this review, we present the latest findings on the antioxidative impacts of semaglutide and draw conclusions about the mechanisms involved.
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    Hepatic effects of GLP-1 mimetics in diabetic milieu: A mechanistic review of involved pathways
    (Elsevier Science Inc, 2025) Yaribeygi, Habib; Kashian, Kiana; Moghaddam, Kimia Imani; Karim, Sheida Rashmeh; Bagheri, Narges; Karav, Sercan; Jamialahmadi, Tannaz
    Patients with diabetic are at a higher risk of developing hepatic disorders compared to non-diabetic individuals. This increased risk can be attributed to the diabetic environment, which triggers and exacerbates harmful pathways involved in both diabetic complications and hepatic disorders. Therefore, it is important to consider the use of antidiabetic agents that offer benefits beyond glycemic control and have positive effects on liver tissues. Glucagon-like peptide-1 (GLP-1) mimetics are a novel class of antidiabetic medications known for their potent blood sugar-lowering effects. Emerging evidence suggests that these drugs also have favorable effects on the liver. However, the precise effects and underlying mechanisms are not yet fully understood. In this review, we aim to provide a mechanistic perspective on the liver benefits of GLP-1 mimetics and outline the mediating mechanisms involved.
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    Impact of statin therapy on CD40:CD40L signaling: mechanistic insights and therapeutic opportunities
    (Springer Heidelberg, 2024) Askarizadeh, Fatemeh; Karav, Sercan; Jamialahmadi, Tannaz; Sahebkar, Amirhossein
    Statins are widely utilized to reduce cholesterol levels, particularly in cardiovascular diseases. They interface with cholesterol synthesis by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase enzyme. Besides their primary effect, statins demonstrate anti-inflammatory and immune-modulating properties in various diseases, highlighting the pleiotropic effect of these drugs. The CD40:CD40L signaling pathway is considered a prominent inflammatory pathway in multiple diseases, including autoimmune, inflammatory, and cardiovascular diseases. The findings from clinical trials and in vitro and in vivo studies suggest the potential anti-inflammatory effect of statins in modulating the CD40 signaling pathway and downstream inflammatory mediator. Accordingly, as its classic ligand, statins can suppress immune responses in autoimmune diseases by inhibiting CD40 expression and blocking its interaction with CD40L. Additionally, statins affect intracellular signaling and inhibit inflammatory mediator secretion in chronic inflammatory diseases like asthma and autoimmune disorders such as myasthenia gravis, multiple sclerosis, systemic lupus erymanthus, and cardiovascular diseases like atherosclerosis. However, it is essential to note that the anti-inflammatory effect of statins may vary depending on the specific type of statin used. In this study, we aim to explore the potential anti-inflammatory effects of statins in treating inflammatory diseases by examining their role in regulating immune responses, particularly their impact on the CD40:CD40L signaling pathway, through a comprehensive review of existing literature.
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    Regulatory effects of statins on CCL2/CCR2 axis in cardiovascular diseases: new insight into pleiotropic effects of statins
    (BMC, 2024) Gholamalizadeh, Hanieh; Ensan, Behzad; Karav, Sercan; Jamialahmadi, Tannaz; Sahebkar, Amirhossein
    BackgroundHMG-CoA reductase inhibitors are well-known medications in the treatment of cardiovascular disorders due to their pleiotropic and lipid-lowering properties. Herein, we reviewed the effects of statins on the CCL2/CCR2 axis.MethodScopus and Pubmed databases were systematically searched using the following keywords: Hydroxymethylglutaryl CoA Reductase Inhibitors, HMG-CoA Reductase Inhibitors, Statins, CCL2, Chemokine, Monocyte Chemoattractant Protein-1 and Chemokine (C-C Motif) Ligand 2. Evidence investigating the role of statin on MCP-1 in CVD was identified and bibliographies were completely evaluated to gather further related studies.ResultsThe anti-inflammatory effects of statins on the CCL2/CCR2 pathway have been widely investigated. Despite inconclusive results, a great body of research supports the regulatory roles of statins on this pathway due to their pleiotropic effects. By disrupting the CCL2/CCR2 axis, statins attenuate the infiltration of monocytes and macrophages into the zone of inflammation and hence down-regulate the inflammatory cascades in various CVDs including atherosclerosis, cardiac remodeling, and stroke, among others.ConclusionCCL2 plays a major role in the pathogenesis of cardiovascular disorders. Down-regulation of CCL2 is proposed as one of the pleiotropic properties of statins. However, more investigations are required to elucidate which statin in what dose exerts a more potent effect on CCL2/CCR2 pathway.