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Öğe Autophagy and mTOR pathways in mouse embryonic stem cell, lung cancer and somatic fibroblast cell lines(Wiley, 2019) Oltulu, Fatih; Kocaturk, Duygu C.; Adali, Yasemin; Ozdil, Berrin; Acikgoz, Eda; Gurel, Cevik; Yavasoglu, N. Ulku Karabay; Aktug, HuseyinEmbryonic developmental stages and regulations have always been one of the most intriguing aspects of science. Since the cancer stem cell discovery, striking for cancer development and recurrence, embryonic stem cells and control mechanisms, as well as cancer cells and cancer stem cell control mechanisms become important research materials. It is necessary to reveal the similarities and differences between somatic and cancer cells which are formed of embryonic stem cells divisions and determinations. For this purpose, mouse embryonic stem cells (mESCs), mouse skin fibroblast cells (MSFs) and mouse lung squamous cancer cells (SqLCCs) were grown in vitro and the differences between these three cell lines signalling regulations of mechanistic target of rapamycin (mTOR) and autophagic pathways were demonstrated by immunofluorescence and real-time polymerase chain reaction. Expressional differences were clearly shown between embryonic, cancer and somatic cells that mESCs displayed higher expressional level of Atg10, Hdac1 and Cln3 which are related with autophagic regulation and Hsp4, Prkca, Rhoa and ribosomal S6 genes related with mTOR activity. LC3 and mTOR protein levels were lower in mESCs than MSFs. Thus, the mechanisms of embryonic stem cell regulation results in the formation of somatic tissues whereas that these cells may be the causative agents of cancer in any deterioration.Öğe The clues in solving the mystery of major psychosis: the epigenetic basis of schizophrenia and bipolar disorder(Pergamon-Elsevier Science Ltd, 2020) Gurel, Cevik; Kuscu, Gokce Ceren; Yavasoglu, Altug; Avci, Cigir BiraySchizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric diseases that are characterized by abnormalities of thought, behaviour, cognition and mood. the genetic findings obtained from past molecular genetics research failed to elucidate the molecular pathogenesis of SZ and BD and this situation showed that the risk factors for these diseases were not solely due to the DNA sequence. on the other hand, evidence from cell, animal and postmortem brain studies suggest that abnormal epigenetic mechanisms are important actors in the etiology of complex diseases such as SZ and BD. in this review, epigenetic evidences that obtained from DNA methylation, post-translational histone modifications and non-coding RNA studies in SZ and BD were summarized and the importance of this evidences for advances in the diagnosis and treatment of SZ and BD were discussed briefly.Öğe The Effects of Different Pressure Pneumoperitoneum Models Created By Standard or Heated-Humidified CO2 Insufflation on Ovary and Peritoneum: an Experimental Study in Rats(Springer Heidelberg, 2022) Gunusen, Ilkben; Akdemir, Ali; Gurel, Cevik; Sargin, Asuman; Taskiran, Dilek; Kuscu, Gokce Ceren; Celik, KubraThere is still controversy over whether structural and morphological changes can be observed in tissues depending on the carbon dioxide (CO2) nature or the applied intra-abdominal pressures (IAP). This study aimed to investigate the effects of different pressure or CO2 nature used for pneumoperitoneum in gynecological laparoscopic surgery on inflammation, DNA damage, oxidative stress, and histopathological changes in ovarian and peritoneal tissue. For this purpose, forty female rats were randomly divided into 6 groups and different pneumoperitoneum models were created in these groups. Rats in group other than control and sham groups received standard (CD) or heated-humidified CO2 (HH) insulations at low (4 mmHg) or high pressure (8 mmHg). The ovary and peritoneum sections were evaluated microscopically for apoptotic index (API) and API scoring was calculated. Tissue and plasma interleukin-6 (IL-6), tumor necrotizing factor-alpha (TNF-alpha), anti-Mullerian hormone (AMH) and 8-hydroxydeoxyguanosine (8-OHdG) levels were analyzed with enzyme-linked immunosorbent assay (ELISA). The most severe changes occurred in the 8CD group microscopically, while the least severe changes occurred in the 4HH group. All histopathological parameters except for ovarian apoptotic index and peritoneal PCNA at low pressure were higher in the CD group. TNF-alpha and 8-OHdG levels were higher in the CD group at both low and high pressures. Standard CO2 caused more prominent histopathological changes at high pressures and systemic inflammation in both pressure groups. The least change between the experimental study groups in terms of histopathological and biochemical was observed in the low-pressure heated-humidified group.Öğe Effects of lercanidipine on traumatic spinal cord injury: an experimental study(Turkish Assoc Trauma Emergency Surgery, 2024) Turk, Caglar; Bahadir, Sinan; Camlar, Mahmut; Gurel, Cevik; Buhur, Aylin; Kuscu, Gokce CerenBACKGROUND: Spinal cord injury is a devastating trauma that leaves survivors at risk for several medical complications throughout their lives. Lercanidipine, a third-generation calcium channel blocker, possesses anti-apoptotic, anti-inflammatory, and antioxidative properties. This study aimed to evaluate the neuroprotective effects of lercanidipine in an experimental spinal cord trauma model. METHODS: Twenty-one Wistar rats were randomly assigned to three groups. Group 1 (G1) underwent laminectomy. Group 2 (G2) were subjected to trauma following laminectomy. Group 3 (G3) were exposed to trauma following laminectomy and treated with lercanidipine. Lercanidipine was administered intraperitoneally for seven days. Histopathological and immunohistochemical evaluations were conducted. RESULTS: Regarding Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, there was no significant difference among the groups. However, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) levels were significantly different across the groups. G2 had significantly higher NF-kappa B levels compared to G1 and G3. CONCLUSION: Lercanidipine, a third-generation calcium channel blocker, is effective against inflammatory responses induced in spinal cord injury. Further studies are required to determine its capability in preventing apoptosis or improving functional recovery. To the best of our knowledge, this study is the first in the literature to examine the neuroprotective effects of lercanidipine on spinal cord injury.Öğe Fluvastatin alleviates doxorubicin-induced cardiac and renal toxicity in rats via regulation of oxidative stress, inflammation, and apoptosis associated genes expressions(Taylor & Francis Ltd, 2022) Kuscu, Gokce Ceren; Gurel, Cevik; Buhur, Aylin; Yavasoglu, Nefise Ulku Karabay; Kose, Timur; Yavasoglu, Altug; Oltulu, FatihDoxorubicin (DOXO) is a cytostatic agent used in the chemotherapy protocol of several cancers for more than 40 years, but usage of this drug in cancer treatment has been limited due to severe renal and cardiac tissue toxicities that may result in death in patients. Fluvastatin (FV) is a fully synthetic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor used as a cholesterol-lowering agent in patients with hypercholesterolemia. Previous studies revealed that FV also exhibits antioxidant, anti-inflammatory, and antitumor activity. Additionally, our previous study indicated that FV exerts a prophylactic effect on DOXO-induced testicular toxicity by preventing lipid peroxidation, supporting the antioxidant system, and regulating the blood-testis barrier-associated genes expression. Herein, we purposed to evaluate the possible therapeutic and the protective effects of FV on the DOXO-induced cardiac and renal toxicitiy model by histochemical, immunohistochemical, biochemical, and real-time polymerase chain reaction (real-time PCR) analyses. Results point out protective use of FV exerts a beneficial effect by repressing lipid peroxidation and by regulating the inducible nitric oxide synthase (iNOS), nitric oxide synthase endothelial (eNOS), nuclear factor kappa-B (NF-kappa B), and Caspase-3 (Casp3) protein and mRNA expressions, which play an important role in mediating DOXO-induced renal and cardiac toxicity mechanisms. In conclusion, FV may be a candidate agent for the prevention of renal and cardiac toxicities in cancer patients receiving DOXO chemotherapy.Öğe Fluvastatin attenuates doxorubicin-induced testicular toxicity in rats by reducing oxidative stress and regulating the blood-testis barrier via mTOR signaling pathway(Sage Publications Ltd, 2019) Gurel, Cevik; Kuscu, Gokce Ceren; Buhur, Aylin; Dagdeviren, Melih; Oltulu, Fatih; Yavasogiu, Nefise Ulku Karabay; Yavasoglu, AltugDoxorubicin (DOX) is an anthracycline derivative antibiotic that still frequently used in the treatment of solid tumors and hematological malignancies. The clinical use of DOX is largely restricted due to acute and chronic renal, cardiac, hematological, and testicular toxicities. Previous studies have indicated that oxidative stress, lipid peroxidation, and apoptosis in germ cells are the main factors in DOX-induced testicular toxicity, but the entire molecular mechanisms that responsible for DOX-induced testicular damage are not yet fully understood. Fluvastatin is a cholesterol-lowering agent that acts by inhibiting hydroxylmethyl glutaryl coenzyme A, the key enzyme for cholesterol biosynthesis. In addition to its cholesterol-lowering effect, fluvastatin showed an antioxidant effect by cleaning hydroxyl and superoxide radicals and this drug could have a protective effect by acting on the mammalian target of rapamycin (mTOR) signal pathway in testicular damage caused by obesity. This study aimed to investigate the possible protective and therapeutic effects of fluvastatin on the DOX-induced testicular toxicity model by histochemical, immunohistochemical, biochemical, and real-time polymerase chain reaction analyses. The present study indicates that fluvastatin may have a protective and therapeutic effect by removing reactive oxygen species and by regulating the mTOR, connexin 43, and matrix metalloproteinase 9 protein and messenger ribonucleic acid expressions, which play an important role in regulating the blood-testis barrier. On the other hand, the use of fluvastatin as a protective/prophylactic agent was found to be more effective than the use of this drug for treatment. In light of this information, fluvastatin may be a candidate agent that can be used to prevent testicular toxicity observed in men receiving DOX treatment.Öğe How Safe Is the Use of Intrathecal Vancomycin?(Elsevier Science Inc, 2022) Demir, Abdulkadir; Camlar, Mahmut; Kuscu, Gokce Ceren; Gurel, Cevik; Oltulu, Fatih; Oren, Merve; Aldag, CeydaBACKGROUND: Central nervous system infection after neurosurgical procedures is a severe complication with high morbidity rates and sometimes mortality. Our experimental study aimed to investigate the biochemical and histopathologic effects of vancomycin on neural tissues when applied to the cisterna magna. METHODS: Wistar albino rats were randomly divided into 4 groups: Control (Group 1) and different vancomycin dose groups (Groups 2, 3, and 4). In Group 1, 0.1 mL cerebrospinal fluid was drained from the cisterna magna and 0.1 mL 0.9% NaCI (normal saline) was administered into the subarachnoid space. In the study groups, 0.1 mL cerebrospinal fluid was drained from the cisterna magna and 0.1 mg/200g rat per day (Group 2), 0.2 mg/200g rat per day (Group 3), and 0.4 mg/200g rat per day (Group 4) vancomycin were administered into the subarachnoid space for 7 days. All rats were sacrificed on the eighth day. Serum super-oxide dismutase and catalase levels were measured. Histopathologic and immunohistochemical analyses were conducted. RESULTS: The findings showed that the administration of 0.2 and 0.4 mg/kg doses had significant differences in superoxide dismutase and catalase activity compared with the controls (P < 0.05). These vancomycin doses also induced the apoptotic process, and the enzyme activity results correlated with immunohistochemical results. CONCLUSIONS: Dose-related neurotoxicity of intrathecal vancomycin was shown at the cellular level. The importance of dose regulation of intrathecal vancomycin has come into view. To our knowledge, this is the first study in the literature that has investigated the neurotoxic effects of vancomycin.Öğe The neuro-restorative effect of adipose-derived mesenchymal stem cell transplantation on a mouse model of diabetic neuropathy(Taylor & Francis Ltd, 2022) Yigitturk, Gurkan; Erbas, Oytun; Karabay Yavasoglu, Nefise Ulku; Acikgoz, Eda; Buhur, Aylin; Gokhan, Aylin; Gurel, CevikDiabetic neuropathy (DN) is the most common degenerative complication associated with Diabetes Mellitus. Despite widespread awareness about DN, the only effective treatments are blood glucose control and pain management. The aim of the current study was to determine the effect of intramuscular adipose-derived mesenchymal stem cell (AMSC) transplantation on sciatic nerves in DN using EMG and histological analyses. A total of 27 mice were randomly divided into three groups: control group, DN group and AMSC group. In EMG, CMAP amplitude in the sciatic nerves was lower, but distal latency was higher in the DN group compared with the control group. CMAP amplitude in the sciatic nerves was higher in the AMSC group compared with the DN group. Distal latency in the sciatic nerve was lower in the AMSC group compared with the DN group. Histologic examination of the tissues in the animals treated with AMSC showed a remarkable improvement in microscopic morphology. Fluorescence microscopy analyses demonstrated that intramuscularly transplanted AMSC was selectively localized in the sciatic nerves. Transplantation of AMSC increased protein expression of S100, cdk2, NGF and DHH, all of which, interfered with DN onset in sciatic nerves. The findings of the present study suggest that AMSC transplantation improved DN through a signal-regulatory effect on Schwann cells, neurotrophic actions and restoration of myelination.Öğe The regulatory effects of clomiphene and tamoxifen on mTOR and LC3-II expressions in relation to autophagy in experimental polycystic ovary syndrome (PCOS)(Springer, 2022) Kuscu, Gokce Ceren; Gurel, Cevik; Buhur, Aylin; Oltulu, Fatih; Akman, Levent; Kose, Timur; Yavasoglu, Nefise Ulku KarabayBackground Polycystic ovary syndrome (PCOS) is a metabolic disease that causes infertility due to anovulation in women in reproductive age. It is known that clomiphene citrate (CC) and tamoxifen citrate (TMX) induce ovulation in women with PCOS. In this study, we aimed to investigate the effects of CC and TMX on the autophagy pathway in PCOS. Methods and results Experimental PCOS model was induced by letrozole (1 mg/kg) in rats by gavage for 21 days. After the last letrozole administration, rats were treated TMX (1 mg/kg) or CC (1 mg/kg) for 5 days. At the end of the experimental procedures, rats in all groups were sacrificed and ovarian tissues were removed. It was observed that mRNA and protein expressions of LC3-II were significantly higher in TMX and CC groups than control and PCOS groups (p < 0.05), while mRNA and protein expressions of mTOR in TMX and CC groups were found significantly lower than control and PCOS groups (p < 0.05). Conclusions In conclusion, present study suggests that TMX and CC induce autophagy in ovaries with PCOS. Autophagy is a promising target for understanding pathophysiology of this disease and for developing more effective and safe new protocols for the treatment of PCOS-related anovulation.
