Louisiana Via Research Day Book 2026

Biomedical Research: Section 2

Biomedical Research: Section 2

Nehal A. Ahmed; Mohamed Mohyeldin, PhD; Hassan Y. Ebrahim, PhD; Md Towhidul Islam Tarun; Khalid El Sayed, PhD 1 University of Louisiana at Monroe, School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy; 2 Department of Pharmacognosy, Faculty of Pharmacy, Alexandria; 3 VCOM-Louisiana 26 (-)-OLEUROPEIN AS A NOVEL METASTATIC CASTRATION-RESISTANT PROSTATE CANCER PROGRESSION AND RECURRENCE SUPPRESSOR LEAD VIA TARGETING PCSK9-LDLR AXIS

Saikat Fakir, MSc; Md Matiur Rahman Sarker, MSc; Madan Sigdel, MSc; Nektarios Barabutis, MSc, PhD School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe 27 GROWTH HORMONE-RELEASING HORMONE ANTAGONISTS COUNTERACT THE EFFECTS OF LPS IN ENDOTHELIAL CORNEAL CELLS

Background: Prostate cancer (PC) is one of the topmost common malignancies in men. Several newly diagnosed patients have a locally advanced disease and distant metastasis at the initial diagnosis time. Castration-resistant PC (CRPC) patients have 100% recurrence incidence despite completing a therapeutic regimen, leading to high mortality. Androgen deprivation therapy and androgen inhibitors are initially effective, but resistance is inevitably developed. Epidemiological studies indicated that the Mediterranean diet, with high olive phenolic contents, is associated with a lower incidence of certain malignancies. This study aims at exploring the mCRPC progression and recurrence suppressive and molecular effects of the major olive leaf phenolic glucoside (-)-oleuropein (OLE). OLE downregulated the levels of proprotein convertase subtlisin/ klexin type 9 (PCSK9) and normalized the low density lipoprotein receptor (LDLR) in PC cells in vitro. Thus, a PCSK9-LDLR protein–protein interaction (PPI) in silico model was generated and used to assess OLE and its aglycone (OA) ability to bind at PCSK9 and thereby interfere with PCSK9-LDLR PPI. OLE perfectly filled the PCSK9 interface versus OA. Both OLE and OA

showed virtual potential to interfere with PCSK9 LDLR PPI. OLE showed modest in vitro viability, migration, and clonogenicity- suppressive effects on diverse human PC cell lines. OLE effectively suppressed mCRPC progression and recurrence in a nude mouse xenograft model. RNA-sequencing results proved the PCSK1, PCSK2, and PCSK9 downregulation in OLE- treated recurrent tumors versus vehicle control. Oleuropein is a novel nutraceutical lead useful for the control of mCRPC progression and the prevention of its recurrence via targeting PCSK9 expression and PPI with LDLR. Keywords: Metastatic castration-resistant prostate cancer; Molecular modeling; Oleuropein; Olive phenolics; PCSK9-LDLR; protein–protein interaction; recurrence.

Background: Growth hormone-releasing hormone (GHRH) regulates the secretion of growth hormone from the anterior pituitary gland, and has been involved in tumor promotion. GHRH Antagonists (GHRHAnt) were developed to oppose the activities of GHRH in malignancies, and have been associated with strong anti-inflammatory and anti-oxidative effects. The present study assesses for the first time the effects of GHRHAnt in inflamed corneal endothelial cells. Our observations suggest that JV-1-36, which is a GHRHAnt, protects the endothelial cells against LPS-induced endothelial leak, reactive oxygen species (ROS) generation and inflammation. Those findings suggest that GHRHAnt may represent an exciting therapeutic possibility in eye disease related to corneal anomalies, including keratitis and Fuch’s endothelial corneal dystrophy.

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2026 Research Recognition Day