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Öğe Altered Stem Cell Receptor Activity in the Ovarian Surface Epithelium by Exogenous Zinc and/or Progesterone(Georg Thieme Verlag Kg, 2015) Oktem, G.; Sahin, C.; Dilsiz, O. Y.; Demiray, S. B.; Goker, E. N. T.; Tavmergen, E.Background: Ovarian surface epithelium (OSE) has the characteristics of a stem cell and the potential for differentiation. Previous studies on this subject have succeeded in deriving oocytes from OSE stem cells, leading to the belief that OSE could be used for infertility treatment. Methods: Each rat (n=10) was subjected to zinc and/or progesterone injection for 5 days after conception. After a 6-day implantation period, ovarian tissues were removed and comprehensive immunohistochemical analysis of stem cell markers was conducted: Sox2, Klf4, Oct3/4, c-Myc, CD117, CD90, SSEA-1 and Notch pathway analysis; Notch1, Jagged1, and Delta1 in the OSE and ovarian stromal cells were evaluated after treatment with zinc, progesterone, or both. Results: Progesterone moderately affected Sox2 expression (p<0.001), while zinc application strongly affected Klf4 and Oct3/4 and immunoreactivity (p<0.001). CD90 immunoreactivity was decreased in the OSE and stroma of the progesterone group (p=0.006) compared with the zinc (p=0.244) and zinc/progesterone groups (p=0.910). On the other hand, SSEA-1 showed moderate staining in the OSE and weak staining in stromal cells in animals treated with zinc (p=0.727), progesterone (p=0.626), and zinc/progesterone (p=0.371), with no differences compared with control. Zinc application affected Notch pathway immunoreactivity, with a significant increase in Notch1 (p=0.0015) and Jagged1 (p<0.001). Conclusions: The expression of putative stem cell markers in the OSE was verified and stem cell receptor activity was raised in the OSE and ovarian stromal cells by zinc and progesterone. Thus, this increased expression allows the therapeutic use of zinc and progesterone in ovary-related infertility and brings a different perspective to reproductive medicine.Öğe Altered Stem Cell Receptor Activity in the Ovarian Surface Epithelium by Exogenous Zinc and/or Progesterone(Georg Thieme Verlag Kg, 2015) Oktem, G.; Sahin, C.; Dilsiz, O. Y.; Demiray, S. B.; Goker, E. N. T.; Tavmergen, E.Background: Ovarian surface epithelium (OSE) has the characteristics of a stem cell and the potential for differentiation. Previous studies on this subject have succeeded in deriving oocytes from OSE stem cells, leading to the belief that OSE could be used for infertility treatment. Methods: Each rat (n=10) was subjected to zinc and/or progesterone injection for 5 days after conception. After a 6-day implantation period, ovarian tissues were removed and comprehensive immunohistochemical analysis of stem cell markers was conducted: Sox2, Klf4, Oct3/4, c-Myc, CD117, CD90, SSEA-1 and Notch pathway analysis; Notch1, Jagged1, and Delta1 in the OSE and ovarian stromal cells were evaluated after treatment with zinc, progesterone, or both. Results: Progesterone moderately affected Sox2 expression (p<0.001), while zinc application strongly affected Klf4 and Oct3/4 and immunoreactivity (p<0.001). CD90 immunoreactivity was decreased in the OSE and stroma of the progesterone group (p=0.006) compared with the zinc (p=0.244) and zinc/progesterone groups (p=0.910). On the other hand, SSEA-1 showed moderate staining in the OSE and weak staining in stromal cells in animals treated with zinc (p=0.727), progesterone (p=0.626), and zinc/progesterone (p=0.371), with no differences compared with control. Zinc application affected Notch pathway immunoreactivity, with a significant increase in Notch1 (p=0.0015) and Jagged1 (p<0.001). Conclusions: The expression of putative stem cell markers in the OSE was verified and stem cell receptor activity was raised in the OSE and ovarian stromal cells by zinc and progesterone. Thus, this increased expression allows the therapeutic use of zinc and progesterone in ovary-related infertility and brings a different perspective to reproductive medicine.Öğe Altered Stem Cell Receptor Activity in the Ovarian Surface Epithelium by Exogenous Zinc and/or Progesterone(Georg Thieme Verlag Kg, 2015) Oktem, G.; Sahin, C.; Dilsiz, O. Y.; Demiray, S. B.; Goker, E. N. T.; Tavmergen, E.Background: Ovarian surface epithelium (OSE) has the characteristics of a stem cell and the potential for differentiation. Previous studies on this subject have succeeded in deriving oocytes from OSE stem cells, leading to the belief that OSE could be used for infertility treatment. Methods: Each rat (n=10) was subjected to zinc and/or progesterone injection for 5 days after conception. After a 6-day implantation period, ovarian tissues were removed and comprehensive immunohistochemical analysis of stem cell markers was conducted: Sox2, Klf4, Oct3/4, c-Myc, CD117, CD90, SSEA-1 and Notch pathway analysis; Notch1, Jagged1, and Delta1 in the OSE and ovarian stromal cells were evaluated after treatment with zinc, progesterone, or both. Results: Progesterone moderately affected Sox2 expression (p<0.001), while zinc application strongly affected Klf4 and Oct3/4 and immunoreactivity (p<0.001). CD90 immunoreactivity was decreased in the OSE and stroma of the progesterone group (p=0.006) compared with the zinc (p=0.244) and zinc/progesterone groups (p=0.910). On the other hand, SSEA-1 showed moderate staining in the OSE and weak staining in stromal cells in animals treated with zinc (p=0.727), progesterone (p=0.626), and zinc/progesterone (p=0.371), with no differences compared with control. Zinc application affected Notch pathway immunoreactivity, with a significant increase in Notch1 (p=0.0015) and Jagged1 (p<0.001). Conclusions: The expression of putative stem cell markers in the OSE was verified and stem cell receptor activity was raised in the OSE and ovarian stromal cells by zinc and progesterone. Thus, this increased expression allows the therapeutic use of zinc and progesterone in ovary-related infertility and brings a different perspective to reproductive medicine.Öğe Assessment of mTOR pathway molecules during implantation in rats(Taylor & Francis Ltd, 2017) Ekizceli, G.; Inan, S.; Oktem, G.; Onur, E.; Ozbilgin, K.Mammalian target of rapamycin (mTOR) is a member of the PI3K/Akt/mTOR signaling pathway that participates in cell growth, proliferation, protein synthesis, transcription, angiogenesis, apoptosis and autophagy. We investigated the role of mTOR and other signaling molecules in the rat uterus during implantation. Female pregnant rats were divided into three groups: embryonic days (ED) 4.5, 5.5 and 6.5 according to vaginal smears. Immunohistochemical staining of mTORC1, mTORC2, IGF1, PI3K, pAkt1/2/3, ERK1 and pERK1/2 was performed on formalin fixed, paraffin embedded uterine tissue samples. pAkt1/2/3 and ERK1 also were analyzed using western blotting. We found that PI3K/Akt/mTOR and ERK/pERK were increased during the implantation period. Different amounts of mTORC1, mTORC2, IGF1, PI3K, pAKT1/2/3, ERK1 and pERK1/2 were expressed in luminal epithelium, decidual cells, embryoblast and trophoblast cells during implantation. We suggest that mTOR and associated signaling molecules may participate in implantation.Öğe Cancer stem cell differentiation: TGF beta 1 and versican may trigger molecules for the organization of tumor spheroids(Spandidos Publ Ltd, 2014) Oktem, G.; Sercan, O.; Guven, U.; Uslu, R.; Uysal, A.; Goksel, G.; Ayla, S.; Bilir, A.Cancer stem cells (CSCs) have the ability to self-renew similar to normal stem cells. This process is linked with metastasis and resistance to chemotherapy and radiotherapy. In the present study, we constructed an in vitro differentiation model for CSCs. CSCs isolated and proliferated for one passage were maintained as monolayers or spheroid-forming cells with serum included media for differentiation process. Differentiation of adhesion molecules and cellular ultrastructural properties were investigated and compared in both monolayer and spheroid cultures. CD133(+)/CD44(+) cancer-initiating cells were isolated from DU-145 human prostate cancer cell line monolayer cultures and propagated as tumor spheroids and compared with the remaining heterogeneous cancer cell bulk population. Microarray-based gene expression analysis was applied to determine genes with differential expression and protein expression levels of candidates were analyzed by immunohistochemistry. Electron microscopy showed detailed analysis of morphology. TGF beta 1 was found to be significantly upregulated in monolayer CSCs. High expression levels of VCAN, COL7A1, 1TG beta 3, MMP16, RPL13A, COL4A2 and TIMP1 and low expression levels of THBS1, MMP1 and MMP14 were detected when CSCs were maintained as serum-grown prostate CSC spheroids. Immunohistochemistry supported increased immunoreactivity of TG beta 1 in monolayer cultures and VCAN in spheroids. CSCs were found to possess multipotential differentiation capabilities through upregulation and/or downregulation of their markers. TGF beta 1 is a triggering molecule, it stimulates versican, Co17A1, ITG beta 3 and, most importantly, the upregulation of versican was only detected in CSCs. Our data support a model where CSCs must be engaged by one or more signaling cascades to differentiate and initiate tumor formation. This mechanism occurs with intracellular and extracellular signals and it is possible that CSCc themselves may be a source for extracellular signaling. These molecules functioning in tumor progression and differentiation may help develop targeted therapy.Öğe Cancer stem cells and nitric oxide(Elsevier, 2023) Taskiran, A.; Demir, A.; Acikgoz, E.; Oktem, G.Cancer stem cells (CSCs) forming the tumor heterogeneity are thought to be the main reason for ineffective and insufficient conventional cancer treatments including surgery, radiotherapy, and chemotherapy and, therefore, causing relapse, metastasis, and multidrug resistance in the long term. CSCs express specific biomarkers on their surface and, thus, differentiate from non-CSCs. The metabolic and signaling activities of CSCs have been shown to be different from those of non-CSCs, and there are still many unknown activities. CSCs share Wnt, Hedgehog, and Notch signaling pathways and many surface markers with embryonic and adult stem cells, indicating that CSCs are the starting point of tumor formation. Deregulation of intrinsic and extrinsic factors of cells induces altered metabolic activities, including the nitric oxide (NO) metabolism, that have a crucial role in the cell fate. CSCs produce high levels of NO and secrete it in the tumor microenvironment involving a wide range of components such as stromal cells, cancer-associated fibroblasts (CAFs), immune cells, nonimmune cells, and blood vessels. Studies have shown that cancer (stem) cell-derived NO promotes chronic inflammation in the tumor microenvironment, pro-tumorigenic activities of CAFs, drug resistance, invasion, and metastasis. These events are reversible by inhibiting cellular NO by NO-releasing drugs or NO donors in cancer therapy either alone or combined with other cytotoxic drugs. Thereby, NO is suggested to be a promising agent for cancer therapy, prevention of the metastatic cascade, and CSC transformation. Further research is needed to elucidate the highly sophisticated activities of NO and CSCs for the advancements of new therapeutic strategies targeting CSCs. © 2023 Elsevier Inc. All rights reserved.Öğe Chemotherapy influences inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) activity on 3D breast cancer cell line(Cognizant Communication Corp, 2006) Oktem, G.; Bilir, A.; Selvi, N.; Yurtseven, M. E.; Vatansever, S.; Ates, U.; Uysal, A.; Omay, S. B.Multicellular tumor spheroids (NITS) are three-dimensional structural forms of tumors grown in vitro in the laboratory. In this study, the aim was to determine the regulation of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expressions on NITS in response to treatment with the commonly used anti-cancer drugs Doxorubicin and Docetaxel. The spheroids were generated using the "liquid overlay" technique. The distribution of both iNOS and eNOS was detected using indirect immunohistochemistry, while the expression of both iNOS and eNOS was measured using Western blots. Additionally, S-phase analysis using 5-bromo-2'-deoxyuridine (BrdU) was done on the MTS after treatment with doxorubicin, docetaxel, and a combination of the two. The Griess method was used to measure nitric oxide (NO) production in the cells. An increase in iNOS immunoreactivity and a decrease in eNOS immunoreactivity were observed after doxorubicin treatment, when compared with the other groups. Furthermore, upregulation of iNOS and downregulation of eNOS were detected in doxorubicin-treated cells using Western blotting. Insignificant iNOS expression was observed in all of the groups, and it was particularly low in the control and drug combination groups. NO production was also found to be significantly high after docetaxel treatment, and cell proliferation decreased after doxorubicin treatment. In conclusion, chemotherapy influences NOS activity differently with the presence of different drugs. The results with iNOS show that doxorubicin is a more effective drug than docetaxel, and a drug combination may play a helpful role in the suppression of tumorigenicity and cancer metastasis. Interestingly, eNOS expression increased after the addition of both docetaxel and the drug combination, and it was found to negatively correlate with the histological grade of the tumor. Therefore, analyzing the expression of both iNOS and eNOS might be very useful for targeting the treatment of breast carcinoma and obtaining better information on prognosis.Öğe Compairment of autophagy and mTOR pathways in mouse embryonic stem cell, lung cancer and somatic fibroblast cell lines in molecular analysis base.(Amer Soc Cell Biology, 2017) Oltulu, F.; Kocaturk, D. Calik; Adali, Y.; Ozdil, B.; Acikgoz, E.; Gurel, C.; Uysal, A.; Yavasoglu, A.; Oktem, G.; Aktug, H.Öğe Cross-talk between ribosome biogenesis, translation, and mTOR in CD133+4/CD44+prostate cancer stem cells(Springer International Publishing Ag, 2020) Binal, Z.; Acikgoz, E.; Kizilay, F.; Oktem, G.; Altay, B.Objective To investigate the gene expression profile of CSCs and to explore the key pathways and specific molecular signatures involved in the characteristic of CSCs. Materials and methods CD133+ /CD44+ CSCs and bulk population (non-CSCs) were isolated from DU-145 cells using fluorescence-activated cell sorting (FACS). We used Illumina HumanHT-12 v4 Expression to investigate gene expression profiling of CSCs and non-CSCs. Protein-protein interaction (PPI) network analysis was performed using the STRING database. Biomarkers selected based on gene expression profiling were visually analyzed using immunofluorescence staining method. An image analysis program, ImageJ (R), was used for the analysis of fluorescence intensity. Results in microarray analysis, we found that many ribosomal proteins and translation initiation factors that constitute the mTOR complex were highly expressed. PPI analysis using the 33 genes demonstrated that there was a close interaction between ribosome biogenesis, translation, and mTOR signaling. the fluorescence amount of mTOR and MLST8 were higher in CSCs compared to non-CSCs. Conclusions the increase in a number of genes associated with ribosome biogenesis, translation, and mTOR signaling may be important to evaluate prognosis and determine treatment approach for prostate cancer (PCa). A better understanding of the molecular pathways associated with CSCs may be promising to develop targeted therapies to prolong survival in PCa.Öğe Doxorubicin-induced senescence promotes resistance to cell death by modulating genes associated with apoptotic and necrotic pathways in prostate cancer DU145 CD133+/CD44+ cells(Elsevier B.V., 2023) Tatar, C.; Avci, C.B.; Acikgoz, E.; Oktem, G.Cancer stem cells (CSCs) are the most important cause of cancer treatment failure. Traditional cancer treatments, such as chemotherapy and radiotherapy, damage healthy cells alongside malignant cells, leading to severe adverse effects. Therefore, inducing cellular senescence without triggering apoptosis, which further damages healthy cells, may be an alternative strategy. However, there is insufficient knowledge regarding senescence induction in CSCs that show resistance to treatment and stemness properties. The present study aims to elucidate the effects of senescence induction on proliferation, cell cycle, and apoptosis in prostate CSCs and non-CSCs. Prostate CSCs were isolated from DU145 cancer cells using the FACS method. Subsequently, senescence induction was performed in RWPE-1, DU145, prostate CSCs, and non-CSCs by using different concentrations of Doxorubicin (DOX). Cellular senescence was detected using the senescence markers SA-?-gal, Ki67, and senescence-associated heterochromatin foci (SAHF). The effects of senescence on cell cycle and apoptosis were evaluated using the Muse Cell Analyzer, and genes in signaling pathways associated with the apoptotic/necrotic pathway were analyzed by real-time PCR. Prostate CSCs were isolated with 95.6 ± 1.4% purity according to CD133+/CD44+ characteristics, and spheroid formation belonging to stem cells was observed. After DOX-induced senescence, we observed morphological changes, SA-?-gal positivity, SAHF, and the lack of Ki67 in senescent cells. Furthermore; we detected G2/M cell cycle arrest and downregulation of various apoptosis-related genes in senescent prostate CSCs. Our results showed that DOX is a potent inducer of senescence for prostate CSCs, inhibits proliferation by arresting the cell cycle, and senescent prostate CSCs develop resistance to apoptosis. © 2023 Elsevier Inc.Öğe Effect of complete hilar versus only renal artery clamping on renal histomorphology following ischemia/reperfusion injury in an experimental model(Verduci Publisher, 2016) Umul, M.; Cal, A. C.; Turna, B.; Oktem, G.; Aydin, H. H.OBJECTIVE: To evaluate the effect of temporary complete hilar versus only renal artery clamping with different duration of warm ischemia on renal functions, and possibly identify a "safe" clamping type and duration of renal ischemia. MATERIALS AND METHODS: Fifty male rabbits have been incorporated to study. Rabbits were subjected to ischemia/reperfusion injury by temporary vascular clamping. Reagents were randomized to 3 experimental groups (only renal artery clamping, complete hilar clamping, sham surgery) and sub-groups were determined according to different clamping times (30 and 60 minutes). Median laparotomy and left renal hilus dissection were performed to sham group. Only artery or complete hilar clamping was performed for 30 or 60 minutes by microvascular bulldog clamps to other reagents. Rabbits were sacrificed 10 days after primary surgery and left nephrectomy performed. Nephrectomy materials were evaluated for the level of nitric-oxide synthase (NOS) immunoreactivity, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity and an electron microscopic examination was performed. RESULTS: NOS immunoreactivity was correlated with the temporary clamping time. We also observed that complete hilar vascular clamping entails an increase on NOS immunoreactivity. MDA levels were similar for all experimental surgery groups (p = 0.42). The SOD activity was decreased among all subgroups compared with sham surgery. But the significant decrease occurred in 30 minutes only artery and 30 minutes complete hilar clamping groups in proportion to sham surgery (p = 0.026 and p = 0.019, respectively). CONCLUSIONS: This current study suggested that only renal artery clamping under 30 minutes is more appropriate during renal surgical procedures requiring temporary vascular clamping.Öğe Effects of sunitinib on immunoreactivity of vimentin, E-cadherin and S100 in kidneys of streptozotocin induced diabetic mice(Taylor & Francis Ltd, 2018) Akarca-Dizakar, S. O.; Aktug, H.; Oltulu, F.; Oktem, G.; Yavasoglu, A.; Acikgoz, E.; Yigitturk, G.; Demir, K.; Uysal, A.Diabetes mellitus (DM) affects many organs including kidney. Tyrosine kinase can cause hypoglycemia and sunitinib is an inhibitor of tyrosine kinase. We investigated the possible effects of sunitinib on the kidney of streptozotocin (STZ) induced type 1 diabetic mice. We used 28 CD 1 type male mice divided into four groups of seven. Type 1 diabetes was induced by injection of STZ. Group 1 was the untreated control. Group 2 comprised non-diabetic mice + sunitinib. Both groups 1 and 2 exhibited normal blood glucose levels. Group 3 comprised STZ treated diabetic mice + saline. Group 4 were diabetic mice + sunitinib treatment. Kidneys were removed after 8weeks. The immunoreactivities of vimentin, E-cadherin and S100 were assessed. Immunostaining of vimentin, E-cadherin and S100 was located in both the glomeruli and tubules of the kidney. We found that the number of vimentin and E-cadherin positive glomeruli and tubules were increased after sunitinib treatment compared to saline treated diabetic mice. The number of vimentin labeled tubules was decreased in the sunitinib treated group compared to diabetic + saline groups. Differences in the number of S100 positive tubules and glomeruli between groups 3 and 4 were not statistically significant. The effect of sunitinib on experimental diabetic mice appears to be related to levels of vimentin, E-cadherin and S100 in the glomeruli and tubules of the kidney, and sunitinib may protect against renal damage from DM.Öğe Enhanced down-regulation of BIRC2 and BIRC3 antiapoptotic proteins with NO-donor DETA NONOate in prostate DU-145 CSCs: potential for combination therapy(Wiley, 2017) Rouhrazi, H.; Turgan, N.; Oktem, G.Öğe Expressional assessment of mouse embryonic stem cell, lung cancer and somatic fibroblast cell lines on the basis of EMT, MAPK and Inflammation.(Amer Soc Cell Biology, 2017) Oltulu, F.; Ozdil, B.; Gurel, C.; Acikgoz, E.; Kocaturk, D. Calik; Adali, Y.; Uysal, A.; Yavasoglu, A.; Oktem, G.; Mukhtarova, G. Gursel; Aktug, H.Öğe Hepatic progenitor cell inhibition during embryonic period with high dose verapamil, liable joint to the cancer therapy(Comenius Univ, 2013) Uslu, S.; Uysal, A.; Bilir, A.; Soner, B. C.; Oktem, G.Cancer stem cells (CSCs) have been observed to share certain characteristics with normal stem cells. It was an important argument for cancer therapy and a successful progenitor inhibition could show us targeted cell type for a novel strategy. In this study, we aimed to constitute an inhibition in different stages of hepatic stem/progenitor cells (HPCs) with verapamil. Expression patterns of alpha-fetoprotein (AFP), c-kit (CD117) and p-glycoprotein were investigated in developing mouse on the embryonic day (E) 15, E18 and E21 to characterize early and late stages of HPCs. Proliferation inhibition with 5-Bromo-2-Deoxyuridin (BrdU) incorporation and maturation inhibition with PAS staining results were supported by morphometrical analysis during these periods. AFP, c-kit and p-glycoprotein immunoreactivity increased especially in E15 but decreased in E18 and E21 of the control groups during embryonic development. Verapamil treatment effected particularly E15 cells and immunoexpression of HPCs significantly decreased. Proliferation inhibition was observed in all embryonic days of mouse with verapamil and this drug inhibited not only maturation of HPCs in E18 and E21 embryos, but also decreased HPC number in the same embryonic period. According to our results, we estimated that similar to the early and late progenitor stages of HPCs, CSCc can also be in different stages in a heterogenic tumour bulk and the difficulty of CSC inhibition could be the main mechanism of tumour relapses. In this study, HPCs inhibition by verapamil in E15 was not observed in E18 and E21. As similar, CSCs treatments targeting different stages may be impotent to cells in tumour initiating cell stage. We can speculate that ineffectiveness of CSC-specific therapies may be attributed to the highly selective specificity of the treatment (Fig. 6, Ref. 28). Full Text in PDF www.elis.sk.Öğe Immunoexpressions of embryonic and nonembryonic stem cell markers (Nanog, Thy-1, c-kit) and cellular connections (connexin 43 and occludin) on testicular tissue in thyrotoxicosis rat model(Sage Publications Ltd, 2015) Oltulu, F.; Aktug, H.; Uysal, A.; Turgan, N.; Oktem, G.; Erbas, O.; Yavasoglu, N. U. Karabay; Yavasoglu, A.In this study, possible thyrotoxicosis-related histological changes in testicular tissues of rats with experimentally induced thyrotoxicosis model were evaluated on cellular connections and stem cell markers. Two experimental groups, thyrotoxicosis and control, each consisting of eight animals were used. Rats in the thyrotoxicosis group were injected intraperitoneally with 3,3,5-triiodo-l-thyronine (50 mu g/100 g body weight/day) for 10 days. At the end of the study, animals in both groups were anesthetized, and blood samples were collected for biochemical analyses. Their testes were dissected out and histological procedure was conducted to perform further histochemical, immunohistochemical analyses and tissue expression analysis by real-time polymerase chain reaction. Expression of the stem cell markers such as c-kit and Thy-1 significantly decreased in the testes of the thyrotoxicosis group compared with the control group; however, Nanog expression was not detected in any of the groups. Similarly, connexin 43 and occludin expressions were also found to be significantly lower in the thyrotoxicosis group. These results on cellular connections are supported with the tissue expression analysis. Our findings are indicative of supporting microenvironmental tissue decay rather than parenchyma damage, which has been actually ignored in the literature. In conclusion, experimental thyrotoxicosis model may have adverse effects on the cell junctional complexes, cell-cell interactions, and pluripotency capacity.Öğe Immunoexpressions of embryonic and nonembryonic stem cell markers (Nanog, Thy-1, c-kit) and cellular connections (connexin 43 and occludin) on testicular tissue in thyrotoxicosis rat model(Sage Publications Ltd, 2015) Oltulu, F.; Aktug, H.; Uysal, A.; Turgan, N.; Oktem, G.; Erbas, O.; Yavasoglu, N. U. Karabay; Yavasoglu, A.In this study, possible thyrotoxicosis-related histological changes in testicular tissues of rats with experimentally induced thyrotoxicosis model were evaluated on cellular connections and stem cell markers. Two experimental groups, thyrotoxicosis and control, each consisting of eight animals were used. Rats in the thyrotoxicosis group were injected intraperitoneally with 3,3,5-triiodo-l-thyronine (50 mu g/100 g body weight/day) for 10 days. At the end of the study, animals in both groups were anesthetized, and blood samples were collected for biochemical analyses. Their testes were dissected out and histological procedure was conducted to perform further histochemical, immunohistochemical analyses and tissue expression analysis by real-time polymerase chain reaction. Expression of the stem cell markers such as c-kit and Thy-1 significantly decreased in the testes of the thyrotoxicosis group compared with the control group; however, Nanog expression was not detected in any of the groups. Similarly, connexin 43 and occludin expressions were also found to be significantly lower in the thyrotoxicosis group. These results on cellular connections are supported with the tissue expression analysis. Our findings are indicative of supporting microenvironmental tissue decay rather than parenchyma damage, which has been actually ignored in the literature. In conclusion, experimental thyrotoxicosis model may have adverse effects on the cell junctional complexes, cell-cell interactions, and pluripotency capacity.Öğe Immunoexpressions of embryonic and nonembryonic stem cell markers (Nanog, Thy-1, c-kit) and cellular connections (connexin 43 and occludin) on testicular tissue in thyrotoxicosis rat model(Sage Publications Ltd, 2015) Oltulu, F.; Aktug, H.; Uysal, A.; Turgan, N.; Oktem, G.; Erbas, O.; Yavasoglu, N. U. Karabay; Yavasoglu, A.In this study, possible thyrotoxicosis-related histological changes in testicular tissues of rats with experimentally induced thyrotoxicosis model were evaluated on cellular connections and stem cell markers. Two experimental groups, thyrotoxicosis and control, each consisting of eight animals were used. Rats in the thyrotoxicosis group were injected intraperitoneally with 3,3,5-triiodo-l-thyronine (50 mu g/100 g body weight/day) for 10 days. At the end of the study, animals in both groups were anesthetized, and blood samples were collected for biochemical analyses. Their testes were dissected out and histological procedure was conducted to perform further histochemical, immunohistochemical analyses and tissue expression analysis by real-time polymerase chain reaction. Expression of the stem cell markers such as c-kit and Thy-1 significantly decreased in the testes of the thyrotoxicosis group compared with the control group; however, Nanog expression was not detected in any of the groups. Similarly, connexin 43 and occludin expressions were also found to be significantly lower in the thyrotoxicosis group. These results on cellular connections are supported with the tissue expression analysis. Our findings are indicative of supporting microenvironmental tissue decay rather than parenchyma damage, which has been actually ignored in the literature. In conclusion, experimental thyrotoxicosis model may have adverse effects on the cell junctional complexes, cell-cell interactions, and pluripotency capacity.Öğe Leukemic cell plasticiy as a resistance mechanism towards tyrosine kinase inhibitors(Wiley-Blackwell, 2016) Baykal, S.; Ates, H.; Yavuz, A. S.; Sezerman, U.; Acikgoz, E.; Oktem, G.; Yuce, Z.Öğe Lithium for treatment and chemo-sensitization: Testing the hypothesis on SH-SY5Y cells in monolaver and 3D-spheroids(Academic Press Inc Elsevier Science, 2007) Oktem, G.; Bilir, A.; Erguven, M.; Altinoz, M.; Yazihan, N.; Kose, T.
