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Background: Acute pancreatitis (APS) is a prevalent acute pancreatic inflammation, where oxidative stress, inflammatory signaling pathways, and apoptosis activation contribute to pancreatic injury., Methods: Pinocembrin, the predominant flavonoid in propolis, was explored for its likely shielding effect against APS provoked by two intraperitoneal doses of L-arginine (250 mg / 100 g) in a rat model., Results: Pinocembrin ameliorated the histological and immunohistochemical changes in pancreatic tissues and lowered the activities of pancreatic amylase and lipase that were markedly elevated with L-arginine administration. Moreover, pinocembrin reinstated the oxidant/antioxidant equilibrium, which was perturbed by L-arginine, and boosted the pancreatic levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Pinocembrin markedly reduced the elevation in serum C-reactive protein (CRP) level induced by L-arginine. Additionally, it decreased the expression of high motility group box protein 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and NOD-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in the pancreas. Furthermore, it also reduced myeloperoxidase (MPO) activity. Pinocembrin markedly downregulated miR-34a-5p expression and upregulated the protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) and Sirtuin 1 (SIRT1) and the gene expression level of the inhibitor protein of NF-κB (IκB-α), along with normalizing the Bax/Bcl-2 ratio., Conclusions: Pinocembrin notably improved L-arginine-induced APS by its antioxidant, anti-inflammatory, and anti-apoptotic activities. Pinocembrin exhibited a protective role in APS by suppressing inflammatory signaling via the TLR4/NF-κB/NLRP3 pathway and enhancing cytoprotective signaling via the miR-34a-5p/SIRT1/Nrf2/HO-1 pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Metformin (MET), an antidiabetic drug, is emerging as a promising anticancer agent. This study was initiated to investigate the antitumor effects and potential molecular targets of MET in mice bearing solid Ehrlich carcinoma (SEC) as a model of breast cancer (BC) and to explore the potential of zein nanoparticles (ZNs) as a carrier for improving the anticancer effect of MET. ZNs were fabricated through ethanol injection followed by probe sonication method. The optimum ZN formulation (ZN8) was spherical and contained 5 mg zein and 30 mg sodium deoxycholate with a small particle size and high entrapment efficiency percentage and zeta potential. A stability study showed that ZN8 was stable for up to three months. In vitro release profiles proved the sustained effect of ZN8 compared to the MET solution. Treatment of SEC-bearing mice with ZN8 produced a more pronounced anticancer effect which was mediated by upregulation of P53 and miRNA-543 as well as downregulation of NF-κB and miRNA-191-5p gene expression. Furthermore, ZN8 produced a marked elevation in pAMPK and caspase-3 levels as well as a significant decrease in cyclin D1, COX-2, and PGE2 levels. The acquired findings verified the potency of MET-loaded ZNs as a treatment approach for BC.