Browsing by Author "Sevim, C."

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INVESTIGATION OF THE EFFECTS OF METFORMIN ON THE miR-21/PTEN/Akt PATHWAY IN HT-29 HUMAN COLORECTAL ADENOCARCINOMA CELL AND HUVEC CO-CULTURE
(2024.01.01) Sevim, C.; Taghizadehghalehjoughi, A.; Kara, M.; Nosyrev, A.E.; Nitulescu, G.M.; Margina, D.; Tsatsakis, A.
Colon adenocarcinoma is a major cause of cancer mortality worldwide. Type 2 diabetic people have an increased risk of developing colorectal cancer compared with nondiabetic people. There are studies showing that metformin inhibits angiogenesis, which is an important stage in cancer metastasis. Our aim was to identify the effects of metformin on miR-21, PTEN, and Akt gene expressions associated with angiogenesis in co-culture conditions established with human colorectal adenocarcinoma cells (HT -29) and human umbilical vein endothelial (HUVEC) cells. Cytotoxicity was evaluated via MTT assay, and PTEN, Akt, and miR-21 expressions were measured by real-time polymerase chain reaction in HUVEC cells under the effects of HT29 cells. Cell viability decreased with increasing doses of metformin, especially in the 160 mu g/mL metformin treatment group. According to real-time PCR results, PTEN was significantly upregulated in 80 and 160 mu g/mL metformintreated cells, and Akt, and miR-21 expressions were downregulated significantly in all metformin treatment groups. An inverse relation was found between PTEN, Akt and miR-21 levels in HUVEC cells under HT29-HUVEC co -culture conditions. Increased PTEN signalling was associated with the prevention of angiogenesis through reducing cell proliferation and migration. The miR-21/PTEN/Akt signalling pathway may have a crucial role in the molecular mechanism of metformin's antiangiogenic effect.
Investigation of the miRNA levels changes to acceptable daily intake dose pesticide mixture exposure on rat mesentery and pancreas
(Elsevier Ltd, 2024) Sevim, C.; Tsatsakis, A.; Taghizadehghalehjoughi, A.; Ozkaraca, M.; Kara, M.; Genc, S.; Mendil, A.S.; Yeni, Y.; Nikolouzakis, T.K.; Ozcagli, E.
Consumers are constantly exposed to a variety of chemical mixtures as part of their everyday activities and lifestyle. Food, water and commercial products are only some examples of the possible ways people get exposed to these mixtures. However, following federal and local guidelines for risk assessment related to chemical exposure, risk analysis focuses on a single substance exposure scenario and not on a mixture, as in real life. Realizing the pronounced gap of this methodology, the real-life risk simulation scenario approach tries to address this problem by investigating the possible effect of long-term exposure to chemical mixtures closely resembling the actual circumstances of modern life. As part of this effort, this study aimed to identify the cumulative effects of pesticides belonging to different classes and commonly used commercial products on long-term exposure with realistic doses. Sprague Dawley rats were given a pesticide mix of active ingredients and formulation chemicals in a daily acceptable dose (ADI) and 10xADI for 90 days. Following thorough everyday documentation of possible side-effects, after 90 days all animals were sacrificed and their organs were examined. Exposure to pesticides particularly affects the miRNA levels at that point will provide us with more information about whether they can be potential biomarkers.
Investigation of the miRNA levels changes to acceptable daily intake dose pesticide mixture exposure on rat mesentery and pancreas
(2024.01.01) Sevim, C.; Tsatsakis, A.; Taghizadehghalehjoughi, A.; Ozkaraca, M.; Kara, M.; Genc, S.; Mendil, A.S.; Yeni, Y.; Nikolouzakis, T.K.; Ozcagli, E.
Investigation of the subchronic effects of low-dose pesticide mixture on rat testes
(2023.01.01) Ömür, A.D.; Sevim, C.; Saglam, Y.S.; Bolat, I.; Genç, S.; Yeni, Y.; Aydin, M.A.; Sunar, S.; Koçak, G.; Akarsu, S.A.
Pesticides are chemical agents used against living things such as insects, rodents, and weeds that cause toxicity in various tissues, including reproductive organs. In order to increase the effectiveness of pesticides, active ingredients are mixed with various formulations. The current study tried to determine the effects of pesticides and their mixtures on testicular tissue in rats. For this purpose, chlormequat chloride (CCC), pirimiphos methyl (PMM), glyphosate ( GLY), tebuconazole (TBZ), chlorpyrifos methyl (CPM), deltamethrin (DLM), and their mix (acceptable daily intake (ADI) and ADIx10) were administried to Sprague-Dawley rats for 90 days. As a result of the examinations, the ADIx10 group showed the most damaging effect by showing a statistical difference in terms of sperm motility and membrane integrity. The GLY group had a similar effect on membrane integrity as the ADIx10 group, while it had a moderately detrimental effect on motility. Degenerations of spermatocytes, necrosis, and edema in intertubular spaces were observed in all pesticide groups. Similarly, 8-hydroxyguanosine (8-OHdG) expression and Caspase-3 expression were moderate in all pesticide groups. Moreover, 8-OHdG expression and Caspase-3 expression were higher in the ADI and ADIx10 groups compared to other groups. As a result, pesticides and their mixtures cause histopathological changes in the testicular tissue of rats and decrease sperm quality.