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    Effects of Functional Pinealectomy on Immunity, Hematopoietic, Gastrointestinal and Urinary Systems in Experimentally Malnutritioned Rats
    (Marmara Univ, Inst Health Sciences, 2024) Turgut, Yaar Bari; Sahin, Cem; Uyanikgil, Yigit; Yilmaz, Mustafa; Tomruk, Canberk; Gencer, Cevat; Cevik, Ozge
    Objective: The aim of this study was to demonstrate morphological changes in immunity, hematopoietic, gastrointestinal and urinary systems in different melatonin (MEL) release situations in a rat model of protein energy malnutrition (PEM). Method: A total of 32 adult male Wistar rats were assigned into four equal groups: normal control; PEM light/dark; PEM light, called functional pinealectomy (Px); and PEM dark. PEM was produced with a 50% restricted diet, Px was produced by keeping rats in continuous light environment for 24 hours, and complete blood count and serum albumin level were analyzed at the end of the 6-week experimental period. Measurements of weights of body and some visceral organs were obtained, biochemical and morphological parameters were analyzed in addition to measurements of malondialdehyde (MDA), total glutatione (GSH), tumor necrosis factor (TNF)-alpha and interleukin-10 (IL-10) in tissue samples. Results: A reduction in the weights of body and visceral organs of animals in the PEM groups was accompanied by hypoalbuminemia, anemia, leukopenia and lymphopenia, and higher MDA, GSH, TNF-alpha and IL-10 levels in visceral tissues. There was a significant decrease in parenchymal cells of the liver and spleen, duodenal villi, lymphoid structures and kidney glomeruli, but there was an increase in the spleen capsule thickness and renal Bowman's space, sinusoidal congestion and fat accumulation in the liver. Importantly, these findings were milder in the PEM dark group, while they were prominent in the PEM light group. Conclusion: This study suggests that MEL has a protective role in reducing the negative effects of PEM, making it a potential therapeutic agent for further investigation.
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    Gingival crevicular fluid Bax, Bcl-xl, interleukin-22, and transforming growth factor beta 1 levels in stage III periodontitis
    (Wiley, 2024) Afacan, Beral; Budak, Utkucan; Altinyurek, Ece Erdem; Ozden, Can; Cevik, Ozge; Kose, Timur; Emingil, Gulnur
    Background Intrinsic apoptosis plays a critical role in immune defense and inflammation. Its dysregulation is involved in various chronic diseases. The B-cell lymphoma 2 (Bcl-2) family primarily mediates this mitochondrial pathway. This study aimed to investigate the proapoptotic Bcl-2-associated X protein (Bax) and antiapoptotic B-cell lymphoma-extra large (Bcl-xl) levels and their association with interleukin-22 (IL-22) and transforming growth factor beta 1 (TGF-beta 1) in the gingival crevicular fluid (GCF) of patients with periodontitis. Methods A total of 75 systemically healthy nonsmokers were enrolled, of whom 23 had stage III periodontitis, 26 had gingivitis, and 26 were periodontally healthy. Whole-mouth clinical periodontal measurements were recorded. Bax, Bcl-xl, IL-22, and TGF-beta 1 levels in the GCF were determined by enzyme-linked immunosorbent assay (ELISA). Data were analyzed using nonparametric statistical tests. Results The periodontitis group had significantly lower GCF Bax levels than the gingivitis group (p < 0.05). The periodontitis and gingivitis groups had higher GCF Bcl-xl levels than the periodontally healthy group (p < 0.05). GCF IL-22 levels were similar in all groups (p > 0.05). The periodontitis group had lower GCF TGF-beta 1 levels than the gingivitis and periodontally healthy groups (p < 0.05). The diseased groups had a lower GCF Bax/Bcl-xl ratio than the healthy controls (p < 0.05). IL-22 was positively correlated with Bax (p < 0.05). Conclusions This is the first study investigating GCF Bax and Bcl-xl levels in periodontal health and disease. Increased GCF Bcl-xl levels and a decreased Bax/Bcl-xl ratio in stage III periodontitis implicate that those apoptotic proteins may be involved in the pathogenesis of periodontal disease. Further studies are needed to enlighten the possible role of Bax and Bcl-xl and their association with IL-22 and TGF-beta 1 in periodontal diseases.
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    Synthesis of novel triazole-urea hybrids and their antiproliferative activity against pancreatic cancer through suppression of eEF2K and induction of apoptosis
    (Elsevier, 2024) Tuere, Asli; Ozdemir, Burcu; Cece, Onur; Armagan, Guliz; Erdogan, Mumin Alper; Erdogan, Omer; Cevik, Ozge
    Pancreatic cancer is one of the deadliest cancers with its highly aggressive and metastatic character and there is a huge unmet need for new drugs treating pancreatic cancer. In the present study, a series of 1,2,4-triazole-urea conjugates have been designed and synthesized as novel candidates of antiproliferative agents against pancreatic cancer cells. Among them, compounds 33, 34, 35 and 38 possesing IC50 values between 0.231 and 0.488 mu M against PANC-1 cells demonstrated the highest anti-proliferative activity. These compounds presenting the highest antiproliferative activity were evaluated for further biological studies. The same four compounds inhibited colony formation in pancreatic cancer cells dose dependently. Western blot study on the selected compounds showed that compounds 33 and 38 significantly reduced eEF2K protein levels in cancer cells. These compounds displayed an effective eEF2K activity suppression by down-regulated levels of unphosphorylated eEF2 in PANC-1 cells. Compounds 33, 34, 35 and 38 were also demonstrated to induce apoptosis and activate caspase 3/7. In silico studies were performed to predict the druggability and ADMET/ properties of the active molecules. In summary, 1,2,4-triazole-urea conjugates developed in this study represent a novel and promising lead structure with anticancer activity against pancreatic cancer achieved through eEF2K activity suppression. Compounds being referred to are the first triazole-urea hybrid molecules found to be effective against pancreatic cancer.