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Öğe Acrylamide, Applied During Pregnancy and Postpartum Period in Offspring Rats, Significantly Disrupted Myelination by Decreasing the Levels of Myelin-Related Proteins: MBP, MAG, and MOG(Springer/Plenum Publishers, 2024) Uremis, Muhammed Mehdi; Uremis, Nuray; Gul, Mehmet; Gul, Semir; Cigremis, Yilmaz; Durhan, Merve; Turkoz, YusufAcrylamide (ACR) is a colorless, odorless, and water-soluble solid molecule. In addition to being an important industrial material, ACR is found in fried and baked carbohydrate-rich foods. ACR is regarded as a typical axonal neurotoxin that induces neuropathy. The brain is protected from oxidative damage by vitamin E, which is regarded as the most powerful fat-soluble antioxidant vitamin. This study aimed to reveal the toxic effect of ACR on the development of myelin in the brain at the molecular level and to examine whether Vitamin E has a neuroprotective effect on the harmful effect of ACR. The study was started by dividing 40 pregnant rats into 4 groups and after lactation, the study was continued with offspring rats (females and males offspring rats) from each group. Offspring rats were equally divided into Control, Vitamin E, ACR, ACR + Vitamin E groups. Following the ACR administration, the Water Maze test was applied to evaluate cognitive function. To evaluate the level of demyelination and remyelination, MBP, MAG, and MOG proteins and mRNA levels were performed. In addition, the degeneration of myelin and glial cells was examined by immunohistochemistry and electron microscopic analysis. Analysis results showed that ACR administration decreased gene and protein levels of myelin-related proteins MBP, MAG, and MOG. The findings were confirmed by histopathological, immunohistochemical, and microscopic examinations. The application of vitamin E improved this negative effect of ACR. It has been observed that ACR may play a role in the pathogenesis of myelin-related neurodegenerative diseases by causing demyelination during gestation, lactation, and post-lactation. In addition, it has been understood that vitamin E supports myelination as a strong neuroprotective vitamin against the toxicity caused by ACR. Our research results suggest that acrylamide may play a role in the etiopathogenesis of demyelinating diseases such as multiple sclerosis in humans since fast-food-type nutrition is very common today and people are chronically exposed to acrylamide.Öğe Anticancer and Anti-Inflammatory Effects of Benzothiazole Derivatives Targeting NF-κB/COX-2/iNOS in a Hepatocellular Carcinoma Cell Line(Galenos Publ House, 2025) Uremis, Muhammed Mehdi; Uremis, Nuray; Ceylan, Mustafa; Turkoz, YusufObjectives: Benzothiazole compounds, characterized by their diverse biological and pharmacological properties, have emerged as promising molecules for suppressing cancer cell proliferation and invasion due to their antiproliferative attributes. Prior research from our laboratory revealed that 2-substituted benzothiazole compounds inhibit the proliferation of glioma and cervical cancer cells and induce apoptosis in pancreatic cancer cells. However, there is limited research on the effectiveness of benzothiazoles against hepatocellular carcinoma cells (HCC). This study sought to elucidate the anticancer potential of 2-substituted benzothiazole derivatives through their modulation of oxidative stress and inflammation mediators. Materials and Methods: Antiproliferative effects of two-step synthesized 2-substituted benzothiazole derivatives were evaluated on HepG2 cells via MTT assay. Apoptosis induction was assessed using Annexin V/PI staining; cell cycle arrest effects were determined through cell cycle analysis; cell migration was examined via wound healing assay; and mitochondrial membrane damage was quantified using JC-1 staining. Spectrophotometric measurements of total antioxidant status (TAS), total oxidant status, superoxide dismutase (SOD), total thiol, and native thiol levels were used to assess cellular redox status. Expression of nuclear factor kappa B (NF-kappa B), an inflammatory marker, was assessed by western blot, while inflammation-related cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase levels were measured using ELISA. Results: This investigation unveiled benzothiazole derivatives' antiproliferative and cytotoxic properties against HepG2 cells (IC50 values of 56.98 pM and 59.17 pM at 24 h, and 38.54 pM 29.63 at 48 h). The synthesized compounds exhibited the ability to suppress cell migration and induce apoptosis, mediated by mitochondrial membrane potential loss (wound-closure rates of 84.0 and 90.4% vs. 51.7% control at 48 h, apoptosis rates of 10.70% and 45.22% vs. 1.02% control). Furthermore, these derivatives reduced SOD activity (A and B at 100 pM p<0.001), TAS levels (A and B at 100 M, p < 0.05, p < 0.001), and dynamic disulfide content. Notably, a decrease in NF-kappa B protein levels, closely associated with inflammation, was observed, along with a subsequent reduction in downstream effectors COX-2 (A and B at 100 pM, p<0.001) and iNOS (A and B at 100 pM, p < 0.001). Conclusion: The findings of this study underscore the antiproliferative effects of benzothiazole derivatives in human HCCs, coupled with their antiinflammatory potential by diminishing NF-kappa B levels.Öğe Antiinflammatory effects of cucurbitacins and sorafenib in Hepg2 cells by modulating the IκB/NF-κB/COX-2 pathway through Akt signaling(Tubitak Scientific & Technological Research Council Turkey, 2025) Uremis, Muhammed Mehd; Turkoz, Yusuf; Uremis, NurayAim: Cucurbitacins possess antitumor, antiproliferative, and antiinflammatory properties. This study aims to examine the antiinflammatory effects of CuD, CuI, and CuE on NF-kappa B, iNOS, COX-2, and Akt and compare their cytotoxic and antiinflammatory effects on HepG2 cells with sorafenib, the primary chemotherapeutic agent used in HCC treatment. Methods: Cytotoxic effects of cucurbitacins and sorafenib on HepG2 cells were evaluated using MTT and LDH assays, along with Annexin V, MMP, and comet assays. Levels of proteins related to the Akt/NF-kappa B pathway and COX-2, iNOS, and NO were also measured. Results: Our study showed that CuD, CuI, CuE, and sorafenib have antiproliferative and cytotoxic effects on HepG2 cells. Cucurbitacins induced apoptosis at lower concentrations than sorafenib and, like sorafenib, reduced p-Akt, p-I kappa B alpha protein levels, and nuclear translocation of NF-kappa B in a dose-dependent manner. Moreover, all compounds significantly decreased COX-2, iNOS, and NO levels, Conclusion: These results indicate that cucurbitacins exert antiinflammatory effects on HepG2 cells by modulating the PI3K/Akt/NF kappa B signaling pathway, thereby reducing COX-2, iNOS, and NO levels. These effects are similar to those of sorafenib.Öğe Cucurbitacin D Inhibits the Proliferation of HepG2 Cells and Induces Apoptosis by Modulating JAK/STAT3, PI3K/Akt/mTOR and MAPK Signaling Pathways(Bentham Science Publ Ltd, 2022) Uremis, Muhammed Mehdi; Uremis, Nuray; Tosun, Emir; Durhan, Merve; Cigremis, Yilmaz; Baysar, Ahmet; Turkoz, YusufBackground: Cucurbitacin D (CuD) is a natural compound that can be isolated in various plant families, mainly from Ecballium elaterium (L.) A. Rich. (E. elaterium). It is a triterpenoid with a broad spectrum of biological activity, including anti-cancer properties. Hepatocellular carcinoma, the aggressive type of liver cancer, is an important public health problem worldwide. Objective: In the present study, we investigated the anticancer effect of CuD treated at different doses on the HepG2 cell line and the underlying mechanism in vitro. Methods: CuD was isolated from the fruit juice of E. elaterium plant, and quantitative analysis was performed using high-performance liquid chromatography. The cell viability effect of purified CuD was determined by the MTT test, and also cell apoptosis and cell cycle arrest effects were determined by flow cytometry. DNA damage was evaluated with the comet test. Proteins and genes involved in PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 signaling pathways were evaluated by western blot and qRT-PCR. Results: CuD showed both antiproliferative and cytotoxic effects against the HepG2 cell line in a dose and time-dependent manner. It was observed that CuD induced apoptosis and blocked the cell cycle in HepG2 cells. It was observed that the expressions of genes and some proteins that play a key role in PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 cascades were dose-dependently down-regulated and led to activatation of the apoptotic pathway. Conclusion: All these results show promise that CuD may have a therapeutic effect in hepatocellular carcinoma.Öğe Cucurbitacin E shows synergistic effect with sorafenib by inducing apoptosis in hepatocellular carcinoma cells and regulates Jak/Stat3, ERK/MAPK, PI3K/Akt/mTOR signaling pathways(Elsevier Science Inc, 2023) Uremis, Muhammed Mehdi; Uremis, Nuray; Turkoz, YusufObjective: Cucurbitacin E (CuE), a natural compound found in medicinal plants such as Ecballium Elaterium, has demonstrated antiproliferative and apoptotic effects in various cancer cell types due to its tetracyclic triterpenoid structure. Sorafenib, a multi-tyrosine kinase inhibitor, is commonly used in hepatocellular carcinoma (HCC) treatment. This study aimed to investigate the anticancer effect of CuE alone and in combination with sorafenib on HepG2 cells.Methods: CuE was extracted from Ecballium Elaterium fruit juice and quantitatively evaluated using HPLC. The effect of sorafenib and CuE on cell growth inhibition was determined using the MTT test. Cell cycle progression and apoptosis were assessed using flow cytometry. Mitochondrial damage was evaluated with & UDelta;& psi;m, and DNA damage was assessed using the comet assay. The expression of Jak2/Stat3, PI3K/Akt/mTOR, MAPK, and Bcl-2 family-related genes and proteins were analyzed using western blot and qRT-PCR, respectively.Results: Both CuE (0.1-5 & mu;M) and sorafenib (0.5-10 & mu;M) exhibited dose-and time-dependent antiproliferative and cytotoxic effects against the HepG2 cell line. Both compounds induced apoptosis in HepG2 cells and halted the cell cycle in the G2/M phase while causing mitochondrial and DNA damage. Both compounds down regulated Jak2/Stat3, PI3K/Akt/mTOR, MAPK signaling pathway proteins, and Bcl-xL levels, while up regulated Caspase-9 and Bax protein levels.Conclusion: Based on the results of this study, it can be concluded that CuE alone or in combination with sorafenib has the potential to be an effective therapeutic option for the treatment of HCC by inducing apoptosis and regulating multiple signaling pathways.Öğe Cucurbitacin I exhibits anticancer efficacy through induction of apoptosis and modulation of JAK/STAT3, MAPK/ERK, and AKT/mTOR signaling pathways in HepG2 cell line(Wiley-Hindawi, 2022) Uremis, Nuray; Uremis, Muhammed Mehdi; Cigremis, Yilmaz; Tosun, Emir; Baysar, Ahmet; Turkoz, YusufHepatocellular carcinoma is a common cancer type, especially among men. Although cucurbitacin I (CuI), widely found in plants belonging to the Ecballium elaterium (E. L) plant family, has been shown to have antitumorigenic properties in many cancer types, its anticancer effect, molecular mechanism, and apoptotic effect mediated by signal pathways on hepatocellular carcinoma have not been fully clarified. In the present study, we investigated the anticancer effect of CuI treated at different doses on the HepG2 cell line and the underlying mechanism in vitro. High-purity CuI was obtained from the E. elaterium plant with the aid of HPLC. The effects of this substance on the viability of cells were studied by the MTT assay. The effects of CuI on cell cycle progression and apoptosis were studied with flow cytometry. DNA breaks were analyzed by the Comet assay method. The proteins and genes involved in the JAK/STAT3, MAPK/ERK, and AKT/mTOR signaling pathways were investigated using Western blot and qRT-PCR, respectively. The results of this study demonstrated that CuI significantly reduced HepG2 cell growth in vitro, induced antiproliferation, and G2/M phase of the cell cycle was interrupted. Practical applications CuI administration was shown to downregulate the levels of proteins in the PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 cascades in HepG2 cells. CuI also reduced the expression of MAPK, STAT3, mTOR, JAK2, and Akt genes in different concentrations. DNA breaks are formed as a result of this effect. CuI, by reducing cell proliferation and promoting apoptosis, was found to have potential as a chemotherapeutic agent of hepatocellular carcinoma.Öğe Dexpanthenol exhibits antiapoptotic and anti-inflammatory effects against nicotine-induced liver damage by modulating Bax/Bcl-xL, Caspase-3/9, and Akt/NF-?B pathways(Wiley, 2024) Uremis, Nuray; Aslan, Meral; Taslidere, Elif; Gurel, ElifChronic tobacco use can lead to liver damage and inflammation due to the accumulation of various toxins in the body. This study aimed to investigate the correlation between the molecular mechanisms of nicotine-induced liver injury, the caspase cascade, and the Akt/NF-kappa B signaling pathway, as well as the protective effects of dexpanthenol (DEX). Male rats were subjected to intraperitoneal injections of nicotine at a concentration of 0.5 mg/kg/day and/or DEX at a concentration of 500 mg/kg/day for 8 weeks. After the treatment period, liver function tests were conducted on serum samples, and tissue samples were analyzed for protein levels of Akt, NF-kappa B, Bax, Bcl-xL, Caspase-3, and Caspase-9, along with histopathological changes. Additionally, assessments of oxidative stress markers and proinflammatory cytokines were carried out. Nicotine administration led to elevated levels of IL-6, IL-1 beta, MDA, TOS, and oxidative stress index, accompanied by decreased TAS levels. Moreover, nicotine exposure reduced the p-Akt/Akt ratio, increased NF-kappa B, Bax, Caspase-3, and Caspase-9 protein levels, and decreased the antiapoptotic protein Bcl-xL levels. DEX treatment significantly mitigated these effects, restoring the parameters to levels comparable to those of the control group. Nicotine-induced liver injury resulted in oxidative stress, inflammation, and apoptosis, mediated by Bax/Bcl-xL, Caspase-3, Caspase-9, and Akt/NF-kappa B pathways. Conversely, DEX effectively attenuated nicotine-induced liver injury by modulating apoptosis through NF-kappa B, Caspase-3, Caspase-9, Bax inhibition, and Bcl-xL activation. Chronic nicotine exposure led to oxidative stress, inflammation, and apoptosis, as evidenced by altered protein levels in Bax/Bcl-xL, Caspase-3/9, and Akt/NF-kappa B pathways. Dexpanthenol treatment effectively countered these effects, highlighting its potential as a therapeutic agent for nicotine-related liver injury.imageÖğe Dose-related effects of dexmedetomidine on wound healing: evaluating fibroblast activation, collagen synthesis, and prolidase activity(Springer London Ltd, 2025) Karaaslan, Erol; Ozkan, Ahmet Selim; Uremis, Nuray; Turkoz, Yusuf; Yildiz, Azibe; Guldogan, Emek; Vardi, NigarBackgroundDexmedetomidine (Dex) is known for extending the time of action and enhancing the analgesic efficacy of local anesthetics. However, its effects on surgical wound healing have not been comprehensively investigated.AimThis study aims to thoroughly examine the effects of subcutaneously administered Dex on wound healing in rats.Methods32 rats in total were randomly distributed into four groups: Control, 3 ml Saline (Group I), 5 mu g/kg Dex (Group II), 30 mu g/kg Dex (Group III), and 60 mu g/kg Dex (Group IV). After the procedure, samples were collected from the surgical wound site on the 7th day. Several wound-healing-related parameters were measured, including arginase, collagen type I, hydroxyproline, Xaa-Pro dipeptidase/prolidase, transforming growth factor-beta (TGF-beta 1), and basic fibroblast growth factor (bFGF). Additionally, the immunoreactivity of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) proteins was assessed to evaluate connective tissue cell proliferation and blood vessel development in the dermis.ResultsHydroxyproline (ng/ml) levels were significantly higher in Groups II, III, and IV compared to Group I. Statistically significant differences were also observed between the groups for Arginase (ng/ml), Collagen Type I (ng/ml), TGF-beta 1 (ng/L), and bFGF (ng/L) values. PCNA immunoreactivity was significantly higher in the 30 mu g/kg group than in other groups. VEGF immunoreactivity was significantly higher in the 5 mu g/kg group.ConclusionThe subcutaneous administration of Dex did not negatively impact wound healing in rats. Histological and biochemical findings showed that doses of 5 and 30 mu g/kg promoted the fastest wound closure and supported homogeneous tissue formation. These results suggest that dexmedetomidine has therapeutic potential in wound healing.Öğe Effects of chronic core training on serum and erythrocyte oxidative stress parameters in amputee football players(Frontiers Media Sa, 2023) Kurtoglu, Ahmet; Konar, Nurettin; Akcinar, Faruk; Car, Bekir; Uremis, Nuray; Turkoz, Yusuf; Eken, OzgurObjective: The positive impact of aerobic exercise on blood oxidative stress parameters is well documented. However, the effect of core exercises on these parameters in amputee football players (AF) remains unclear. Therefore, this study aims to investigate the impact of core exercises on blood oxidative stress parameters in this population.Methods: Experimental method was adopted in the study. Eleven elite AF players participated in the study. The participants were divided randomly into two groups a core exercise group (CEG) and a control group (CG). Blood measurements were taken before and after the 8-week core exercise program. Blood measurements included erythrocyte Total Oxidant Status (eTOS), erythrocyte Total Antioxidant Status (eTAS), erythrocyte oxidative stress index (eOSI), serum nitric oxide (sNO), serum Total Oxidant Status (sTOS), serum Total Antioxidant Status (sTAS), serum oxidative stress index (sOSI), serum total thiol (sTT), serum native thiol (sNT), and serum disulfide (sDS) parameters were studied.Results: According to the results of the study, a significant difference was found between the 0th and eighth week pre-aerobic training load (ATL) sTOS (p = .028) values of CEG values. A significant difference was found in sTOS (p = .028) and sOSI (p = .028) values after the 0th and eighth-week pre-ATL. A significant difference was found in the sTOS (p = .043) and sOSI values (p = .043) of CG at week 0th and eighth-week pre-ATL.Conclusion: Overall, the results suggest that core exercises had a positive effect on blood oxidative stress parameters in AF players by reducing blood total oxidant levels.Öğe Effects of larazotide acetate, a tight junction regulator, on the liver and intestinal damage in acute liver failure in rats(Sage Publications Ltd, 2021) Caliskan, Ali Riza; Gul, Mehmet; Yilmaz, Ismet; Otlu, Baris; Uremis, Nuray; Uremis, Muhammed Mehdi; Kilicaslan, IlkayBackground and Aim The epithelial cells are the strongest determinants of the physical intestinal barrier. Tight junctions (TJs) hold the epithelial cells together and allow for selective paracellular permeability. Larazotide acetate (LA) is a synthetic octapeptide that reduces TJ permeability by blocking zonulin receptors. In this study, we aimed to investigate the effects of LA, a TJ regulator, on the liver and intestinal histology in the model of acute liver failure (ALF) in rats. Materials and Methods The thioacetamide (TAA) group received intraperitoneal (ip) injections of 300 mg/kg TAA for 3 days. The TAA+LA(dw) (drinking water) group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of TAA. The LA(dw) group received 0.01 mg/mL LA orally. The TAA + LA(g) (gavage) group received prophylactic 0.01 mg/mL LA via oral gavage for 7 days before the first dose of TAA. The LA(g) group received 0.01 mg/mL LA via oral gavage. While liver tissue was evaluated only with light microscopy, intestinal samples were examined with light and electron microscopy. Results Serum ammonia, AST, and ALT levels in the TAA group were significantly higher than in control groups (all p < 0.01). Serum ALT levels in the TAA + LA(dw) group were significantly lower than in the TAA group (p < 0.05). However, serum ammonia and ALT levels did not differ between the TAA and other groups. Serious liver damage in the TAA group was accompanied by marked intestinal damage. There was no significant difference between the TAA and TAA + LA(dw) groups and TAA and TAA + LA(g) groups for liver damage scores. However, intestinal damage scores significantly decreased in the TAA + LA(dw) group compared to the TAA group. In the TAA + LA(dw) group, fusion occurred between the surface epithelial cells of neighboring villi and connecting regions formed as epithelial bridges between the villi. Conclusion Our findings suggest that LA reduced intestinal damage by acting on TJs in the TAA-induced ALF model in rats.Öğe EVALUATION OF BLOOD ZONULIN LEVELS, INFLAMMATORY PROCESSES AND NEURONAL CHANGES IN CHILDREN WITH AUTISM SPECTRUM DISORDER(Medicinska Naklada, 2022) Kartalci, Gulsen; Demir, Arzu Caliskan; Kartalci, Sukru; Uremis, Nuray; Turkoz, YusufBackground: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by symptoms such as limited, and repetitive behavior patterns and disordered social interaction and communication. The etiology of Autism Spectrum Disorder (ASD) is not clearly known, it has been emphasized that the immune-inflammatory system may also play a role in this disease. This study aimed to evaluate in intestinal permeability, food antigen-antibody levels, inflammatory processes, and neuron damage in patients with ASD. Subjects and methods: Thirty-five children between the ages of 3-12 with ASD and 35 controls were included in the study. Both participants' height and weight were measured, and the parents filled the Socio-demographic Data and the Gastrointestinal Systems (GIS) Symptoms Form. Venous blood samples were collected, and serum zonulin, anti-gliadin Ig A and Ig G, IL6, TNF-alpha, TGFJ3, S100B, and NSE levels were measured by ELISA. Results: Serum zonulin levels in the ASD group were found to be significantly lower. IL-6 and TGF-beta were found to be significantly higher in the ASD group. There was no difference between the two groups in terms of serum anti-gliadin Ig A and Ig G and TNF-alpha values. Also, GIS symptoms, NSE and SlOOB levels were found similar between two groups. Conclusions: Although findings showing low zonulin levels and increased inflammatory processes in ASD were found in this study, no difference was found in the parameters of brain damage. The findings show that intestinal permeability does not decrease in ASD and that inflammatory processes may play a role in ASD.Öğe Evaluation of serum TWEAK, TRAIL, and oxidative stress markers in rosacea patients(Wiley, 2022) Durmaz, Imge; Turkmen, Dursun; Altunisik, Nihal; Uremis, Nuray; Uremis, Muhammed Mehdi; Sener, Serpil; Turkoz, YusufBackground Rosacea is a chronic inflammatory skin disease of unknown pathogenesis. TWEAK and TRAIL are two cytokines thought to have a role in the pathogenesis of some inflammatory and autoimmune diseases. Aims The purpose of this study was to examine TWEAK and TRAIL serum levels and oxidative stress markers in patients with rosacea. Material and Method Forty rosacea patients and 40 sex- and age-matched healthy controls were involved in the study. Serum TWEAK and TRAIL levels were evaluated with ELISA kits. Serum total antioxidant status, total oxidant status, total thiol, native thiol, disulfide levels were evaluated, and oxidative stress index was computed. Results Serum levels of TWEAK, TRAIL, and oxidative stress markers did not differ statistically in the patients and controls. Both TWEAK and TRAIL levels in the patients were detected to be statistically higher in male than in female. Conclusion TWEAK and TRAIL may not have a systemic effect in rosacea, unlike other inflammatory diseases. More studies are needed to investigate the role of TWEAK and TRAIL in rosacea.Öğe Impaction of the polylactic membrane or hydrofiber with silver dressings on the interleukin-6, tumor necrosis factor-?, transforming growth factor-?3 levels in the blood and tissues of pediatric patients with burns(Turkish Assoc Trauma Emergency Surgery, 2021) Demircan, Mehmet; Gurunluoglu, Kubilay; Bag, Harika Gozde Gozukara; Kocbiyik, Alper; Gul, Mehmet; Uremis, Nuray; Gul, SemirBACKGROUND: We aimed to evaluate the effects of two different burn dressings, hydrofiber with a silver (HFAg) and polylactic membrane (PLM), on altering the levels of important biomarkers Interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-alpha), Transforming growth factor-beta(3) (TGF-beta(3)) in blood and burnt tissue in children with second-degree burns. METHODS: Children between the ages of one to 16 years, with 25-50% second-degree partial-thickness burns of the total body surface area were included in this study. Patients in the PLM group were dressed with PLM in a typical way according to the manual. The HFAg group was dressed with HFAg and a sterile cover. During and at the end of the 21-day treatment, blood and skin tissue samples were taken from the two burn and control groups. IL-6, TNF-alpha, and TGF-beta beta(3) levels were evaluated in blood and tissue samples from all groups, and the results were analyzed statistically. RESULTS: In the PLM group, IL-6 and TNF-alpha levels decreased early days in both serum and tissue samples to reach normal ranges compared with the HFAg group. In the PLM group, TGF-beta(3) levels were elevated than in other groups for two weeks. CONCLUSION: In this study, we found that PLM controls inflammation earlier in both systemic and burn tissue. We also found that PLM increased the level of TGF-beta(3), which may be associated with the prevention of the development of hypertrophic scar in the burn wound, in the blood and burn tissue during this study.Öğe Investigating EGFR-VEGF-mediated apoptotic effect of cucurbitacin D and I combination with sorafenib via Ras/Raf/MEK/ERK and PI3K/Akt signaling pathways(Springer, 2024) Uremis, Nuray; Turkoz, Yusuf; Uremis, Muhammed Mehdi; Cigremis, Yilmaz; Salva, EmineSorafenib, which is a type of systemic multi-kinase inhibitor drug, is used for first-line therapy in treating hepatocellular carcinoma (HCC). In this study, the anticarcinogenic effects of sorafenib-cucurbitacin D and sorafenib-cucurbitacin I combination on HepG2 cell line were investigated. Cell inhibition, migration, apoptosis, cell cycle distribution, mitochondrial membrane potential (Delta psi m), colony formation, and wound healing were investigated by applying cucurbitacin D and I alone or in combination with sorafenib to HepG2 cells. In addition, in order to reveal how cucurbitacins affect the signal pathways known to affect sorafenib; proteins and genes involved in VEGF, EGFR, MMP-2, caspase cascade, PI3K/AKT/mTOR, Raf/MEK/ERK signaling pathways were assessed by western blot and qRT-PCR. It has been shown that cucurbitacin D and I have an antiproliferative effect at low concentrations and show a synergistic effect when combined with sorafenib. Combined administrations induced apoptosis by increasing caspase-9, Bax activity and inhibiting Bcl-xL activation, blocking the cell cycle in G2/M phase and causing loss of Delta psi m. The combinations also suppressed MMP-2 and VEGF, reduced cell migration. The combined cucurbitacin-sorafenib applications inhibited the expression of proteins and genes involved in EGFR and PI3K/AKT/mTOR, Raf/MEK/ERK signaling pathways. Due to showing the synergetic effect of cucurbitacins with sorafenib and their targeting of similar signaling pathways reveal that their combination may increase the efficacy of sorafenib by suppressing angiogenic, metastatic and proliferative activity in HCC.Öğe Investigation of apoptotic effects of Cucurbitacin D, I, and E mediated by Bax/Bcl-xL, caspase-3/9, and oxidative stress modulators in HepG2 cell line(Wiley, 2024) Uremis, Muhammed Mehdi; Turkoz, Yusuf; Uremis, NurayCucurbitacins, natural compounds highly abundant in the Cucurbitaceae plant family, are characterized by their anticancer, anti-inflammatory, and hepatoprotective properties. These compounds have potential as therapeutic agents in the treatment of liver cancer. This study investigated the association of cucurbitacin D, I, and E (CuD, CuI, and CuE) with the caspase cascade, Bcl-2 family, and oxidative stress modulators in the HepG2 cell line. We evaluated the antiproliferative effects of CuD, CuI, and CuE using the MTT assay. We analyzed Annexin V/PI double staining, cell cycle, mitochondrial membrane potential, and wound healing assays at different doses of the three compounds. To examine the modulation of the caspase cascade, we determined the protein and gene expression levels of Bax, Bcl-xL, caspase-3, and caspase-9. We evaluated the total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH), Total, and Native Thiol levels to measure cellular redox status. CuD, CuI, and CuE suppressed the proliferation of HepG2 cells in a dose-dependent manner. The cucurbitacins induced apoptosis by increasing caspase-3, caspase-9, and Bax activity, inhibiting Bcl-xL activation, causing loss of Delta psi m, and suppressing cell migration. Furthermore, cucurbitacins modulated oxidative stress by increasing TOS levels and decreasing SOD, GSH, TAS, and total and native Thiol levels. Our findings suggest that CuD, CuI, and CuE exert apoptotic effects on the hepatocellular carcinoma cell line by regulating Bax/Bcl-xL, caspase-3/9 signaling, and causing intracellular ROS increase in HepG2 cells.Öğe Investigation of the cardiotoxic effects of parenteral nutrition in rabbits(W B Saunders Co-Elsevier Inc, 2020) Gurunluoglu, Kubilay; Gul, Mehmet; Kocbiyik, Alper; Koc, Ahmet; Uremis, Nuray; Gurunluoglu, Semra; Bag, Harika GozukaraIntroduction: Parenteral nutrition (PN) is used for the intravenous delivery of nutrients to patients who cannot take food orally. However, it is not clear whether PN also negatively impacts cardiac tissue. The present empirical study investigated the cardiac effects of PN in rabbits. Methods: The effects of PN were examined in three groups of rabbits: animals in the PN + fasting group (n = 14) had been fully fasted before receiving a full PN dose via an intravenous central catheter; the PN + oral feeding group (n = 14) received half of the daily calorie requirement as a half dose of PN via an intravenous central catheter; the third group consisted of controls (n = 14) with full enteral feeding and full enteral fluid intake with no PN and no central venous catheter. Al the end of the 10-day study period, the rabbits were subjected to echocardiographic examination and euthanized. Blood and tissue samples were obtained from all groups. DNA was isolated from nucleated blood cells. Tissue samples were examined by both light and electron microscopy, relative telomere length was determined from DNA, and blood samples were analyzed biochemically. Results: At the end of the study, there were no statistically significant differences in weight change between the three groups. Echocardiography revealed minimally impaired diastolic function in the PN + fasting group compared to the other groups. Biochemical and histopathological analyses, relative telomere length determination, and electron micrographs showed significant cardiac damage in the PN + fasting group but not in the PN + oral feeding group or the control group. The blood biochemical analyses showed hyperglycemia and a low insulin level in the PN + fasting group but not in the other two groups. Conclusions: A combination of PN and fasting may damage the cardiac muscle cells of rabbits via a mechanism involving hyperglycemia and oxidative stress. Additional enteral feeding may protect against the destructive effects of PN on cardiac tissue. (C) 2019 Elsevier Inc. All rights reserved.Öğe Larazotide acetate reduces the frequency of bacterial translocation in the thioacetamide-induced liver failure in rats(Elsevier, 2020) Caliskan, Ali Riza; Harputluoglu, Muhsin Murat; Otlu, Baris; Gul, Mehmet; Ozerol, Elif; Uremis, Nuray; Dertli, Ramazan[Abstract Not Available]Öğe Linalool exhibits therapeutic and protective effects in a rat model of doxorubicin-induced kidney injury by modulating oxidative stress(Taylor & Francis Ltd, 2022) Altinoz, Eyup; Oner, Zulal; Elbe, Hulya; Uremis, Nuray; Uremis, MuhammedThe aim of the present study was to investigate the therapeutic and protective effects of linalool against doxorubicin (DOX)-induced kidney injury. Forty-eight Wistar rats were divided into 8 groups as follows; Control, DOX [20 mg/kg, intraperitoneal (ip) single dose DOX], linalool (LIN50 and LIN100; 50 mg/kg and 100 mg/kg linalool via ip for 5 days, respectively), DOX + LIN50 and DOX + LIN100 (20 mg/kg single dose of DOX via ip on first day and 50 mg/kg and 100 mg/kg linalool via ip, respectively), LIN50 + DOX and LIN100 + DOX (50 mg/kg and 100 mg/kg linalool via ip for 5 days, respectively and 20 mg/kg single dose of DOX via ip on fifth day). Doxorubicin led to a significant increase in the level of malondialdehyde (MDA) in the kidney, whereas superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels decreased remarkably when compared with control. On the other hand, LIN supplementation before and after DOX treatment led to a significant decrease in MDA and also increases in SOD, CAT and GSH levels. DOX caused significant increases in the levels of blood urea nitrogen (BUN) and creatinine (Cr) levels in the plasma, while LIN supplementation as a therapeutic and preventive agent led to significant decreases in BUN and Cr levels. The current study demonstrated that LIN supplementation after or before DOX treatment can led to therapeutic and preventive effects against DOX-induced renal damage.Öğe Measurement of oxidant and antioxidant levels in liver tissue obtained from patients with liver transplantation: A case-control study(Elsevier, 2022) Akbulut, Sami; Uremis, Muhammed Mehdi; Sarici, Kemal Baris; Uremis, Nuray; Hargura, Abdirahman Sakulen; Karakas, Serdar; Dogan, Ufuk GunayObjective: This study aimed to compare oxidant and antioxidant substance accumulation in the liver tissues of patients with chronic liver disease (recipients) who underwent liver transplantation (LT) with living liver donors (LLDs) who underwent living donor hepatectomy (LDH).Methods: This prospective study included 160 recipients (LT group) and 40 LLDs (LLD group). During surgery, a piece of liver tissue measuring a minimum of 10 x 10 mm was obtained from the edge of the right lobe of the liver of recipients and LLDs, incubated for 10 min in saline to remove blood, and stored at -70 degrees C until biochemical analysis was performed. Catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), myeloperoxidase (MPO), prolidase, reduced glutathione (GSH), malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), total thiol, native thiol, and disulfide levels were measured in stored liver tissues.Results: There was a statistically significant difference between LT and LLD groups in terms of age (p < 0.001), body mass index (p = 0.019), GSH-Px (p < 0.001), SOD (p = 0.001), MPO (p < 0.001), prolidase (p < 0.001), GSH (p < 0.001), and MDA (p = 0.003) values in favor of the LT group. Furthermore, there was a statistically significant difference between LT and LLD groups in terms of CAT (p < 0.001), TAS (p < 0.001), TOS (p < 0.001), OSI (p < 0.001), total thiol (p < 0.001), native thiol (p < 0.001), and disulfide (p < 0.001) values in favor of the LLD group. There were no differences between the groups in terms of sex.Conclusion: This study demonstrated that it is possible to assess the extent of oxidative stress in liver tissues by measuring the levels of antioxidant enzymes, oxidants, or the end-products of oxidative stress. With the use of optimum and minimally invasive methods, quantifying these molecules will potentially help evaluate the extent of liver disease and prognostication of liver cirrhosis.Öğe Ninety Sixth-Hour Impact of Scalding Burns on End Organ Damage, Systemic Oxidative Stress, and Wound Healing in Rats Treated With Three Different Types of Dressings(Oxford Univ Press, 2024) Aslan, Mehmet; Gul, Mehmet; Uremis, Nuray; Akbulut, Sami; Gurunluoglu, Semra; Ozsoy, Eda Nur; Turkoz, YusufIn this study, we investigated the effects of 3 different burn dressing treatments, including experimental, silver, and modern dressing materials, on systemic oxidative stress in rats with severe scald burns within the first 96 h. The rats were divided into five groups: a burn group (n = 10), a polylactic membrane group (n = 10), a silver sulfadiazine group (n = 10), a curcumin group (n = 10), and a control group (n = 10), consisting of equal numbers of female and male rats. In the first 4 groups, 30% of the rats' total body surface area was scalded at 95 degrees C. The burn group was not treated. Each group was treated with group-name dressing material. The control group was neither treated nor burned. The rats were sacrificed, and blood and tissue samples were obtained at the 96th hour when severe effects of oxidative stress developed postburns. Systemic inflammatory biomarkers and oxidative stress parameters were examined. In addition, apoptosis and organ damage in liver, kidney, lung, and skin tissues were evaluated biochemically and histopathologically. When the parameters were statistically analyzed, we found that the systemic levels of oxidative stress and inflammatory damage to liver, kidney, and lung tissues were lower in the 3 treated groups than in the burn group. We believe that the dressing material's efficacy in the treatment of severe burns may be dependent on its ability to combat oxidative stress and inflammation.
