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en Palmitate-increased TGF-β1 Gene Expression and p-Smad2/3 Protein Levels Attenuated by Chicoric Acid in Patients with Type 2 Diabetes Mellitus بیوشیمی Biochemistry مقالات اصلی Original Article <div class="WordSection1">Background: The transforming growth factor beta1 (TGF-β1) signaling pathway plays a critical role in the pathogenesis of Type 2 diabetes mellitus (T2DM). Modulating this pathway may offer therapeutic benefits for managing T2DM. Chicoric acid (CA), a polyphenolic compound with reported anti-diabetic properties, has shown potential in metabolic regulation; however, its precise molecular mechanisms remain unclear. This study aimed to investigate the effects of palmitate and CA on the TGF-β1 signaling pathway in peripheral blood mononuclear cells (PBMCs) from newly diagnosed T2DM patients and healthy controls. Methods: A total of 40 participants, including 20 newly diagnosed T2DM patients and 20 age-matched healthy individuals (40–60 years), were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and treated with palmitate and CA. The expression of TGF-β1 mRNA was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels of Smad2/3 and phosphorylated Smad2/3 (p-Smad2/3) were assessed via western blot analysis. Results: Palmitate stimulation significantly upregulated TGF-β1 gene expression and increased p-Smad2/3 protein levels in PBMCs. However, CA treatment effectively attenuated these palmitate-induced elevations in TGF-β1 expression and p-Smad2/3 protein levels. Additionally, a positive correlation was observed between TGF-β1 expression and p-Smad2/3 protein levels. Conclusions: These findings suggest that CA may act as an inhibitor of the TGF-β1 signaling pathway, potentially contributing to T2DM management by downregulating TGF-β1/Smad signaling. Further studies are warranted to explore its therapeutic potential in diabetes treatment. <div align="center" style="text-align:center"> <hr align="center" noshade="noshade" size="2" style="color:#0f243e" width="100%" ></div> </div> <div aria-label="Page Break" class="cke_pagebreak" contenteditable="false" data-cke-display-name="pagebreak" data-cke-pagebreak="1" style="page-break-after:always" title="Page Break"></div> Chicoric acid, Palmitate, Smad signaling, Transforming growth factor-beta 1, Type 2 diabetes mellitus. 540 548 http://rbmb.net/browse.php?a_code=A-10-1195-2&slc_lang=en&sid=1 Zahra Arab Sadeghabadi 100319475328460021661 100319475328460021661 No 1: Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Nasrin Ziamajidi 100319475328460021662 100319475328460021662 No Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Science, Hamadan, Iran. Roghayeh Abbasalipourkabir 100319475328460021663 100319475328460021663 No Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Science, Hamadan, Iran. Zohreh khajehahmadi 100319475328460021664 100319475328460021664 No Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Science, Hamadan, Iran. Sina Mohagheghi 100319475328460021665 100319475328460021665 No Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Science, Hamadan, Iran. Heidar Tayebinia 100319475328460021666 100319475328460021666 No Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Science, Hamadan, Iran. Roohollah Mohseni Mohseni.r@skums.ac.ir 100319475328460021667 100319475328460021667 Yes Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.