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Background: Diabetes mellitus (DM) is common metabolic disease that poses a major risk to public health and fertility. Previous studies indicate that DM may cause male infertility by triggering oxidative stress and germ cell apoptosis in the testis. Due to the undesirable effects of known antidiabetic drugs, scientists have begun to investigate the use of alternative drugs to control infertility complications observed in men. In this context, present study aimed to investigate the possible antiapoptotic effect of losartan against DM-induced testicular germ cell apoptosis. Methods and results: Expreimental DM model was induced by intraperitoneal injection of streptozocin (STZ, 55 mg/kg) to 28 rats, which were then randomly assigned to 4 groups; 1 mL saline solution was given to DM + saline group by oral gavage, 5 mg/kg/day oral losartan was given to DM + low-dose losartan, 20 mg/kg/day oral losartan was given to DM + mid-dose losartan and, 80 mg/kg/day oral losartan was given to DM + high-dose losartan group for 4 weeks. Bax, Bcl-2 and cleaved-Caspase 3 immunoexpression, terminal-deoxynucleotidyl transferase dutp nick end labeling (TUNEL), Annexin-V and Real Time PCR analyses performed to evaluate antiapoptotic effects of losartan on diabetic rats’ testis. In addition, biochemical analyzes carried out to evaluate change in oxidative stress. Conclusion: The results showed that losartan may have dose-related antiapoptotic effects on rats’ testis via decreasing oxidative stress. © 2022, The Author(s), under exclusive licence to Springer Nature B.V., Ege University Research Foundation: 16-TIP-092, This study was supported by the Ege University Research Fund [grant number 16-TIP-092 (to Altuğ Yavaşoğlu)].

Purpose To investigate the histological efficacy of ranibizumab and zoledronic acid in an experimentally induced endometriosis model as compared with danazol, buserelin acetate and dienogest. Methods Endometrial implants were introduced in 52 female Wistar albino rats, which were then randomly divided into six groups. The animals were, respectively, given dienogest, danazol, buserelin acetate, zoledronic acid, ranibizumab and 0.9% NaCl. After 4 weeks, the volumes and histopathological properties of the implants were evaluated and the implants were excised completely at the third laparotomy. A histopathological scoring system was used to evaluate the preservation of epithelia. Endometrial explants were evaluated immunohistochemically. Results Among the groups, the histological score was significantly lower in the zoledronic acid and ranibizumab groups compared with the controls (p < 0.001). There were no significant differences regarding ellipsoidal volume levels between groups (p > 0.05). However, there was a statistically significant difference regarding cell numbers according to the degree of Bcl-2, NF-kappa B, and CD31 staining (p < 0.001). There was no statistically significant difference in Bcl-2, CD31, or NF-kappa B staining in the binary comparisons between the other groups (p > 0.05). For Bcl-2 staining, the staining rate of the group treated with zoledronic acid was significantly lower compared with the dienogest and danazol groups (p < 0.05). The staining rates of CD31 and NF-kappa B were significantly lower in the zoledronic acid and ranibizumab groups compared with the controls (p < 0.05). Conclusion According to these results, zoledronic acid and ranibizumab may be putative candidates for the treatment of endometriosis., Technological and Scientific Research Council of Turkey (TUBITAK) [213S002], This study was funded by The Technological and Scientific Research Council of Turkey (TUBITAK) (213S002).

Doxorubicin (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., Ege University Scientific Research Projects Coordination Unit [18-TIP-016], This study was supported by the Ege University Scientific Research Projects Coordination Unit [grant number 18-TIP-016 (to FO)].

Background 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., Ege University Research Fund [BAP-17-TIP-029], This study was supported by the Ege University Research Fund [Grant number BAP-17-TIP-029 (to Altug Yavasoglu)].

Aim: The aims of present study were revealing possible ischemia-reperfusion damage caused by pneumoperitoneum on ovarian tissue and investigating effects of vitamin D on this ovarian damage.Materials and Methods: Twenty-one adult female Sprague Dawley rats were used in this study and these rats were divided into three groups, each contained seven subjects: Sham Group, Ischemia-Reperfusion and Ischemia-Reperfusion +Vitamin D GroupIn Ischemia-Reperfusion Group, desufflation was performed 60 minutes after pneumoperitoneum induction and intraabdominal pressure was normalized for 30 minutes. In the Ischemia-Reperfusion + Vitamin D group, pneumoperitoneum induction was performed after 500 mg/kg of vitamin D administration. After the reperfusion period, the ovaries were collected, and ischemia reperfusion damage was evaluated. Histochemical staining was performed to evaluate the follicular degeneration, vascular congestion, inflammation, hemorrhage and edema parameters in the ovaries. In addition, immunohistochemical PCNA (Proliferating cell nuclear antigen) staining was performed to evaluate DNA repair mechanisms. In biochemical analyzes, AMH (Anti-Mullerian hormone), MDA (Malondialdehyde), TAC (Total antioxidant capacity) and SOD (Superoxide dismutase) levels were examined in the ovaries.Results: In histological evaluation, significant differences were found between the groups and also the PCNA values were significantly higher in the Ischemia-Reperfusion Group compared to the Sham and Ischemia-Reperfusion +Vitamin D Groups (p, Amaç: Çalışmanın amacı pneumoperitoneumun over dokusu üzerinde oluşturduğu olası iskemi reperfüzyon hasarının gösterilmesi ve D vitamininin bu hasar üzerindeki etkilerinin araştırılmasıdır.Gereç ve Yöntem: Çalışmamızda her biri 7 denekten oluşan 3 grup şeklinde Sprague Dawley cinsi dişi sıçanlar kullanılmıştır. Pneumoperitoneum sağlandıktan 60 dakika sonra desuflasyon gerçekleşt r lm ş ve 30 dakika boyunca intraabdominal basınç normalize edilmiştir eperfüzyon periyodunu takiben overler çıkarılmış ve iskemi reperfüzyon hasarı değerlend r lm şt r Histolojik olarak, overlerde foll küler dejenerasyon, vasküler konjesyon, nflamasyon, hemoraji, ödem ve DNA tamir mekanizmalarını değerlendirmek için PCNA (Proliferating cell nuclear antigen) düzeyine, biyokimyasal olarak da plazma AMH (Anti müllerian hormon) ve overde MDA (Malondialdehid), TAC (Total antioksidan kapasite) ve SOD (Süperoksid dismutaz) düzeyine bakılmıştırBulgular: Histolojik olarak gruplar arasında farklılıklar saptanmış ve ayrıca PCNA değerleri iskemi grubunda sham ve D vitamini grubuna göre anlamlı düzeyde yüksek bulunmuştur (p

Amaç: Bu çalışmanın amacı, sıçanlarda maternal uterin arter ligasyonuna bağlı olarak gelişen intrauterine büyüme geriliğinde kondrogenez ve osteogenezin Wnt/β-catenin ve S100 ekspresyonlarının immünohistokimyasal ve histomorfometrik olarak değerlendirilmesi.Gereç ve Yöntem: Gebe sıçanlar 3 gruba ayrıldı (n=5). Kontrol grubuna cerrahi veya anestezi uygulanmadı. Deney grubunda, 18. gebelik gününde bilateral maternal uterin arterlere ligasyon yapıldı. Sham grubuna uterin arter ligasyonu dışındaki tüm cerrahi işlem uygulandı. Fetuslar gebeliğin 20. gününde alındı, sol proksimal tibiadan büyüme plağı ve zonların kalınlıkları, trabeküler sayı ve kalınlıkları, kortikal kalınlıklar histomorfometrik olarak değerlendirildi. Büyüme plağında β-catenin ve S100 ekspresyonları immunohistokimyasal olarak değerlendirildi.Bulgular: Deney grubunda büyüme plağı (p0.05). Aynı zamanda daha düşük sayıda trabekülar yapı (p, Aim: The aim of this study is to investigate the effects of intrauterine growth retardation depending on maternal uterine artery ligation, Wnt/β-catenin and S100 expression immunohistochemistry and histomorphometrically on chondrogenesis and osteogenesis of fetal rats.Materials and Methods: Maternal rats were randomly divided into 3 groups (n=5). No surgery or anesthesia were applied in control group. Bilaterally the maternal uterine arteries were ligated on gestational day 18 in experimental group. Although all surgical procedures were performed in sham group, the uterine artery ligation were not made. Fetuses were taken on gestational day 20, thicknesses of growth plate and zones, trabecular number and thickness and cortical thickness were evaluated with the histomorphometrically in samples from left proximal tibia. The expressions of β-catenin and S100 immunohistochemically were evaluated in the growth plate.Results: Thicknesses of growth plate (p0.05). Also trabecular numbers were lower (p

Zinc pyrithione (ZnPT) is one of the components used in antifouling paints and can be an alternative to classical toxic chemicals such as organotin. However, there is still remarkable concern about the environmental safeness of ZnPT due to rapid transchelation and degradation into several metabolites that have their own toxicity. The effect after acute exposure of ZnPT is investigated on Mediterranean mussels exposed to 20 and 40 mu g/L concentrations for 48 and 96 h and antioxidant responses [superoxide dismutase (SOD), and reduced glutathione (GSH)], genotoxicity [micronuclei (MN) frequency], apoptotic and histological changes were determined. Severe histological changes in hepatopancreas and gill tissues of mussels were observed in ZnPT exposed groups due to dose-dependent increase. ZnPT also caused a dose-dependent increase of TUNEL-positive cell count in the mussel tissues, especially in the hepatopancreas. Increasing in SOD activities and decreasing in GSH levels in both ZnPT concentrations compared to the control were observed. MN and binuclei numbers in all exposure groups were significantly increased. The results of the present study demonstrate that acute exposure to ZnPT could cause an adverse effect on mussel tissues at especially higher concentrations., Manisa Celal Bayar University BAP project [2014-154], The study is supported by Manisa Celal Bayar University BAP project (2014-154).

Endoplasmic reticulum (ER) stress has been reported to play a role in the pathogenesis of intrauterine growth retardation and preeclampsia, especially implantation failure. Although in vitro ER stress studies in human trophoblast cell line have been conducted in recent years, the influence of Thapsigargin on intracellular dynamics on calcium homeostasis has not been proven. Here, the effects of ER stress and impaired calcium homeostasis on apoptosis, autophagy, cytoskeleton, hypoxia, and adhesion molecules in 2D and spheroid cultures of human trophectoderm cells were investigated at gene expression and protein levels. Thapsigargin caused ER stress by increasing GRP78 gene expression and protein levels. Human trophectoderm cells displayed different characterization properties in 2D and spheroids. While it moves in the pathway of EIF2A and IRE1A mechanisms in 2D, it proceeds in the pathway of EIF2A and ATF6 mechanisms in spheroids and triggers different responses in survival and programmed cell death mechanisms such as apoptosis and autophagy. This led to changes in the cytoskeleton, cell adhesion molecules and cell-cell interactions by affecting the hypoxia mechanism., 218S882, Funding This study was carried out by T?BI?TAK within the content of the 1002 project with the number 218S882.

The current cancer studies focus on the molecular-targeting diagnostics and their interaction with surrounding microenvironment, however, there are some missing points on the characterization of the cells with their topological differences and elemental composition. Glioblastoma multiforme (GBM) which is an astrocytic aggressive brain tumour with short survival time. GBM and astrocyte cells may differ at molecular level and the elemental and topological evaluation of these cells are vital for a definition of new potential targets for cancer research. Here, we report the topology and chemistry of cancer (GBM) and healthy (astrocyte) cells by atomic force microscopy (AFM), scanning electron microscopy (SEM) supported with energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS), for the first time. Additionally, F-actin Immunofluorescence staining and Real-Time Polymerase chain reaction (RT-PCR) techniques were performed. Actin related genes were similar in level of gene expression; however, F-actin protein intensities were different. The gene expressions related to the invasion were elevated in GBM cells. Morphologically, GBM cells were found to be longer and narrower while astrocytes were shorter and more disseminated based on AFM. Furthermore, roughness values of these cells were relatively close to each other. SEM-EDS analysis demonstrated that elongated GBM cells exhibited several filopodial protrusions whereas the astrocyte surfaces were rougher in lamellipodial area. Our investigation provides considerable further insight into rapid cancer cell characterization field in terms of its combinatorial spectroscopic and microscopic approach.

BACKGROUND: 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.

Although in vitro endoplasmic reticulum (ER) stress studies have been carried out using Tunicamycin in human trophoblast cell lines in recent years, the effect of calcium homeostasis impaired by the effect of Thapsigargin on cell survival - death pathways have not been clearly demonstrated.Here, the effects of ER stress and impaired calcium homeostasis on cell death pathways such as apoptosis and autophagy in 2-dimensional and 3-dimensional cell cultures were investigated using the HTR8 / SVneo cell line representing human trophoectoderm cells and the ER stressor Thapsigargin. By using Real Time PCR, gene and immunofluorescence analyzes were studied at the protein level.In this study, it has been established that the Thapsigargin creates ER stress by increasing the level of GRP78 gene and protein in 2 and 3 dimensions of human trophoectoderm cells and that cells show different characterization properties in 2 and 3 dimensions. It has been determined that while it moves in the direction of EIF2A and IRE1A mechanisms in 2 dimensions, it proceeds in the direction of EIF2A and ATF6 mechanisms in 3 dimensions and creates different responses in survival and programmed cell death mechanisms such as apoptosis and autophagy.With forthcoming studies, it is thought that the effects of Thapsigargin on the intrinsic pathway of apoptosis and the linkage of the autophagy mechanism, the examination of the survival-death pathways in the co-culture model with endometrial cells, therapeutic target molecules that will contribute to the elucidation of intracellular cell dynamics may increase the success of implantation.

WOS: 000512563000001, PubMed: 32013622, Aim of the study: Biologic reconstruction using tumor-bearing bone autografts devitalized by liquid nitrogen or extracorporeal irradiation (oncological sterilization) is a safe and effective method in musculoskeletal surgery. the purpose of this study was to examine the effects of these two oncological sterilization methods on nerve recovery. Methods: A total of 48 rats were randomly divided into 3 groups as autograft, irradiation and liquid nitrogen groups. A nerve defect created in the right sciatic nerve was reconstructed with an autograft obtained from the nerve itself. Group I underwent reconstruction with standard nerve autograft. Group II and Group III underwent reconstruction with devitalized nerve autograft treated through extracorporeal irradiation and liquid nitrogen, respectively. the left sciatic nerves of the rats served as control. Electromyography, motor function test and histomorphological analysis were performed to assess the nerve recovery on the 3rd (early stage) and 4th months (late stage). Results: Electrophysiological assessment revealed better results in irradiation group compared with liquid nitrogen group in terms of myelinization and axonal regeneration. Motor performance of the autograft group was slightly better than the other groups. Histologically, autograft group demonstrated better results compared with other groups. Late-stage assessments revealed high rates of myelinization in the graft segment in liquid nitrogen group and in the segment distal to the graft in irradiation group. Conclusions: This study has demonstrated that nerve autografts treated by oncological sterilization methods may be used for nerve reconstruction in limb salvage surgery. However, further studies are needed to clarify the applicability of these methods., Ege University Scientific Research FoundationEge University [15-TIP-013], This work was supported by Ege University Scientific Research Foundation (15-TIP-013).

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.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).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.

Objective: There is a strong relationship between the cancer stem cells (CSCs) and poor prognosis, metastasis and recurrence. In addition to this CSCs are resistant to chemotherapy and radiotherapy. Therefore, current treatment approaches may be ineffective to elimination of CSCs. The tumor cells have various adaptations for escaping from immune cells. The human leukocyte antigen (HLA) -G, which expressions restricted with fetal tissues and HLA-E are kind of tumor immune evasive adaptations. In this study, we aimed to investigate the relationship between the CSCs and immune evasive adaptations of breast tumors.Methods: We immunohistochemically evaluated that the expressions of cluster of differentiation (CD) 44, CD133, Homeobox protein Nanog, octamerbinding transcription factor (Oct) 3/4, HLA-G and HLA-E in the advanced stage breast cancer tissues (n=10) and the non-malignant breast biopsies (n=10).Results: We detected that the significantly increased expressions of especially Nanog (p

Diabetes is a multisystem disorder and its effects are observed on the reproductive system. One of the main causes of testicular tissue damage is diabetes-induced overproduction of reactive oxygen species and glycated end products. The main objectives of this study were to investigate the possible effects of agomelatine (AG) and gallic acid (GA) in suppressing oxidative stress in Type I diabetes induced testicular damage. A total of 28 adult male rats were included in the study. Diabetes was induced by intraperitoneal injection of streptozocin (STZ, 55mg/kg) to 21 rats, which were then randomly assigned to 3 groups; 1mL saline solution was given to the diabetes+saline group by oral gavage, 20mg/kg/day oral AG was given to the diabetes+AG group, and 20mg/kg/day oral GA was given to the diabetes+GA group for 4 weeks. Tumor necrosis factor α (TNFα), nitric oxide synthase 2 (NOS2), fibronectin and vascular endothelial growth factor (VEGF) were used for the investigation of inflammation, fibrosis and vascular structures. The terminal-deoxynucleoitidyl-transferase mediated nick end-labeling assay (TUNEL) was used to detect apoptosis. Testicular tissue total antioxidant capacity values were tested by biochemical analysis. AG treatment showed an improvement on biochemical parameters and histopathological appearance on the rat testes. GA showed dose-related regenerative effects on biochemical parameters. Histologically, a minimal healing effect was determined on the testes damage. In conclusion, it was observed that AG is a potentially beneficial agent for reducing testicular damage by decreasing oxidative stress level. However, GA was seen to have a poor therapeutic effect.

Embryonic 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.

Colorectal carcinoma (CRC) is one of the most fatal types of cancer in both women and men, and, unfortunately, patients are often diagnosed at an advanced stage. Cancer stem cells (CSCs) are associated with poor prognosis, metastasis, and recurrence, as well as chemotherapy and radiotherapy resistance. Therefore, different treatment alternatives are needed to facilitate the elimination of CSCs. One such approach is immunotherapy; however, tumor cells can evade immune cells by alteration of the expression patterns of human leukocyte antigens (HLA). In this study, we immunohistochemically investigated the expression patterns of CSC-specific markers CD44, CD133, Nanog, and Oct3/4, and immunosuppressive molecules HLA-G and -E in advanced CRC tumor tissues and noncancerous colon biopsies. We found significantly increased CD44, Nanog, Oct3/4, HLA-G, and HLA-E expression in the CRC tumor tissues compared with the noncancerous colon biopsies. These findings suggest that some tumor cells may be CSC-like and that the increased expression of HLA-G and HLA-E may be considered as an immune-evasive adaptation. Therefore, the nonclassical major histocompatibility complex class Ib antigens HLA-G and HLA-E may be potential targets in the elimination of CRC-CSCs. However, more detailed studies are required to support our findings.

bilge, okan/0000-0002-8993-2271; Taskiran, Dilek/0000-0002-4505-0939 WOS: 000390431000008 PubMed: 27881053 Purpose: The aim of the present study is to investigate the protective effects of oxytocin (OT) on diabetic neuropathy (DNP) in rats. Materials and methods: Eighteen rats were used to induce diabetes using single dose streptozotocin (STZ, 60 mg/kg). Diabetic DNP was verified by electromyography (EMG) and motor function test on 21st day following STZ injection. Six rats served as naive control group and received no drug (n=6). Following EMG, diabetic rats were randomly divided into three groups and administered with either 1ml/kg saline or 80 g/kg OT or 160 g/kg OT intraperitoneally for four weeks. Then, EMG, motor function test, biochemical analysis (plasma lipid peroxides and glutathione), histological, and immunohistochemical analysis of sciatic nerves (bax, caspase 3, caspase 9, and NGF) were performed. Results: Diabetic rats developed neuropathy, which was apparent from decreased compound muscle action potentials amplitudes and prolonged distal latency in saline-treated rats (p

Objective Diabetic neuropathy (DNP) is a frequent and serious complication of diabetes mellitus (DM) that leads to progressive and length-dependent loss of peripheral nerve axons. The purpose of the present study is to assess the neuroprotective effects of levetiracetam (LEV) on DNP in a streptozotocin (STZ)-induced DM model in rats. Methods Adult Sprague-Dawley rats were administered with STZ (60 mg/kg) to induce diabetes. DNP was confirmed by electromyography (EMG) and motor function test on 21st day following STZ injection. Study groups were assigned as follows; Group 1: Naive control ( n = 8), Group 2: DM + 1 mL/kg saline ( n = 12), Group 3: DM + 300 mg/kg LEV ( n = 10), Group 4: DM + 600 mg/kg LEV ( n = 10). LEV was administered i.p. for 30 consecutive days. Then, EMG, motor function test, biochemical analysis (plasma lipid peroxides and total anti-oxidant capacity), histological and immunohistochemical analysis of sciatic nerves (TUNEL assay, bax, caspase 3, caspase 8 and NGF) were performed to evaluate the efficacy of LEV. Results Treatment of diabetic rats with LEV significantly attenuated the inflammation and fibrosis in sciatic nerves and prevented electrophysiological alterations. Immunohistochemistry of sciatic nerves showed a considerable increase in bax, caspase 3 and caspase 8 and a decrease in NGF expression in saline-treated rats whereas LEV significantly suppressed apoptosis markers and prevented the reduction in NGF expression. Besides, LEV considerably reduced plasma lipid peroxides and increased total anti-oxidant capacity in diabetic rats. Conclusions The results of the present study suggest that LEV may have therapeutic effects in DNP through modulation of anti-oxidant and anti-apoptotic pathways.

Background/aim Losartan, an antihypertensive drug, is highly preferred in patients with diabetes mellitus (DM) and hypertension because of its retarding effect on diabetic nephropathy. In this study, we investigated the potential therapeutic effect of different doses of losartan on hepatic damage in a streptozotocin (STZ, 50 mg/kg)-induced DM model in rats. Materials and methods In this study, five different groups were formed: control, DM, low-dose losartan (5 mg/kg), mid-dose losartan (20 mg/kg), and high-dose losartan (80 mg/kg). Liver tissues of experimental groups were evaluated immunohistochemically for TUNEL, iNOS, eNOS, VEGF, and NF-κB pathways. In addition to immunohistochemical analysis, analyses of SOD and MDA, which are oxidative stress markers, were also performed and the results were evaluated together. Results When biochemical and immunohistochemical findings were evaluated together, it was found that the results obtained from the mid-dose losartan group were closer to those of the control than the other groups. Conclusion This study indicated that mid-dose losartan administration may have a therapeutic effect by inhibiting apoptosis and regulating iNOS, eNOS, VEGF, and NF-κB protein expressions in DM-induced hepatic damage.

EgeUn###, Doxorubicin (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. © The Author(s) 2019.

WOS: 000473763100013, PubMed ID: 30806476, AIM: To investigate the effects of fluorescein-sodium on neural tissues. MATERIAL and METHODS: Twenty-one Wistar rats were randomly divided into three experimental groups: control (group 1) and fluorescein-sodium groups with different doses (groups 2 and 3). In the control group, craniectomy following with durotomy was performed with the help of a loupe microscope, and a dry sponge was overlayed to the brain tissue. In the study groups, the open dura was covered with a sponge soaked with 0.02 mg (group 2) and with 0.2 mg (group 3) fluorescein sodium following craniectomy. Three weeks postoperatively, rats were sacrificed for the histopathologic evaluations. RESULTS: Fluorescein-induced apoptosis occurs in a dose-dependent manner in rats' neurons. It was determined that neuron and neuroglial cell TUNEL staining was statistically different among the three groups (p

Background Spinal cord injury (SCI) may result in neuromotor, sensory, and autonomic function damages. Edema because of spinal cord trauma can reach serious dimensions. The aim of this study was to histologically evaluate the effects of duraplasty on neural tissues. Methods Twenty-eight Wistar rats were randomly divided into 4 experimental groups: group 1 received laminectomy without SCI (sham); group 2 received laminectomy and SCI with the weight drop method; group 3 received laminectomy, SCI, and duraplasty within the first 6–8 hours of SCI; and group 4 received laminectomy, SCI, and duraplasty after 24 hours of SCI. The neurologic functions of the rats were tested periodically. All animals were euthanized 28 days after the surgery. Histopathologic and immunohistochemical evaluations were performed, and Kruskal-Wallis tests were used for statistical comparison of data between the groups. Results There was no significant difference in the Tarlov examination scores from different time points between the groups. The number of neurons stained with nuclear factor kappa beta was higher in group 3 than groups 1 and 4. The number of neurons stained with terminal deoxynucleotidyl transferase dUTP nick-end labeling was higher in group 2 than group 3. Conclusions Decompressive laminectomy is a procedure frequently used in spinal trauma surgery. However, it is often unclear whether the decompression is fully adequate. Our results will aid the development of further studies regarding the reliability of duraplasty in the treatment of SCI.

Objectives/Hypothesis To examine and compare the neuroprotective effects of dexamethasone, oxytocin, and resveratrol administration on regeneration after facial nerve crush injury in a rat model. Study Design Prospective, randomized, controlled animal study. Methods A crush-type facial nerve injury was performed on the right side of all rats (injury group [IG]), whereas there was no injury on the left side (sham group [SG]). These main groups were divided into five subgroups: 1) no medicine (control); 2) physiological serum; 3) dexamethasone; 4) oxytocin; and 5) resveratrol (Res) administered (intraperitoneal injection) for 28 days. Functional recovery was evaluated by daily eye-blink reflex and facial electromyography. Nerve–muscle degeneration and regeneration, apoptosis, and intercellular connections were evaluated in histopathological and immunohistochemical examinations. Results Recovery time of the postinjury eye-blink reflex demonstrated faster recovery in IG + Res when compared with the other subgroups. In peak-to-peak amplitude values, a significant increase was observed in the dexamethasone (P = 0.007) and oxytocin subgroups (P = 0.004) and was even more apparent in the resveratrol subgroup (P < 0.001). Nerve regeneration is apparent in the resveratrol subgroup. Apoptotic changes were evaluated immunohistochemically with TUNEL and Caspase 3 and 6 antibodies staining. Caspase 3 and 6 immunoexpressions of resveratrol and oxytocin subgroups were moderate when compared with dexamethasone subgroup. Except for the resveratrol subgroup, which had an increase in expression, the majority of subgroups were similar to SG in terms of intercellular connections (Connexin 32 and 43). Conclusion Resveratrol leads to the best outcome after facial nerve crush injury in rats when compared with dexamethasone and oxytocin, even though these agents demonstrate a significant improvement in facial nerve regeneration. Level of Evidence N/A. Laryngoscope, 125:E356–E364, 2015

Amaç: Bu çalışmada, deneysel olarak tirotoksikoz oluşturulan sıçanlarda, tirotoksikoza bağlı olarak ovaryum yapısında, özellikle tiroid hormon reseptörleri içeren oosit, kumulus hücreleri ve gran ü losa hücrelerinde oluşabilecek histolojik değişimler ile doku rejenerasyon yeteneği ve kapasitesinin , kök hücre belirteçleri açısından imm ü nohistokimyasal olarak araştırılması amaçlan dı . Gereç ve Yöntem: Her biri 8 sıçandan oluşan 2 çalışma grubu oluşturul du. Tirotoksikoz grubu dişi sıçanlara 10 gün i ntraperitoneal 500µgr/kg/gün 3,3',5-Triiodo-L-thyronine enjekte edil di . On birinci gün tüm hayvanlara anestezi uygulan dı , biyokimyasal değerlendirmeler için 5 cc kan alındıktan sonra dekapite edilerek ovaryumları çıkarıl dı . Ovaryumlar immünohistokimyasal incelemeler için %4’ lük paraformaldehit fiksatifi içine alın dı . Rutin immünohistokimyasal takip ve boyamalar yapıl arak tüm örnekler ış ık mikroskobunda değerlendiril di . Bulgular: İmmünohistokimyasal boyamalar sonucunda c -kit ve Thy -1 ekspresyonu kontrol grubuna göre tirotoksikoz grubunda belirgin düzeyde azalmış, Nanog ekspresyonu ise tirotoksikoz grubunda artmış olarak bulundu. Tirotoksi kozlu sıçanlarda c -kit ve Thy -1’in azalması , tirotoksikozda stromal büyüme desteğinin azalmasına ve mikroçevre bozunumuna neden ol du. Sonuç: Tirotoksikozda Nanog ekspresyonunun artışı, foliküler yapıları ve oositleri korumak adına dokunun katabolik süreç (tiroid hormonlarının hemen tüm hücrelerde metabolizmayı hızlandırmasına bağlı olarak) artışına rağmen reaktif olarak mikroçevreyi koruma çabası olarak yorumlan dı ., Aim: In this study, it was aimed to investigate the possible histological changes in the ovarian structure and particularly in the oocytes, cumulus cells and granulosa cells containing thyroid hormone receptors, tissue regeneration capability and capacity in terms of stem cell markers immunohistochemically by experimentally-induced thyrotoxicosis in rats. Materials and Methods: Two study groups were formed (eight rats for each group); 500µgr/kg/day 3,3',5-Triiodo-L- thyronine was injected intraperitoneally to female rats in thyrotoxicosis group during ten days. In 11 th day, all animals were anesthesized, 5 cc blood was drawn for biochemical evaluation and then all were decapitated in order to remove ovaries. Ovaries were placed in 4% paraformaldehyde fixative for immunohistochemical investigation. Immunohystochemical processing and staining were performed routinely and all samples were evaluated by light microscopy.Results: As a result of immunohistochemical staining, c-kit and Thy-1 expressions were found to be significantly decreased in the thyrotoxicosis group compared with the control group, whereas Nanog expression was increased in the thyrotoxicosis group. Decrease in c-kit and Thy-1 expression in the thyrotoxicosis group cause d a reduction in the stimulatory effects of the growth factors on oocytes, cumulus and granulosa cells. Conclusion: Decreased levels of c-kit and Thy-1 in rat model of thyrotoxicosis lead to a decrease in stromal growth support and deterioration of microenvironment. Elevated levels of Nanog expression in thyrotoxicosis was interpreted as an effort to protect the microenvironment for the sake of follicles and oocytes despite the increase in catabolic processes (as a result of increased metabolism in almost all cells due to thyroid hormones).

Amaç: Zoledronik asit (ZA) uygulanmış meme kanser kök hücrelerinde (KKH), kanser kök hücresi ve otofaji ile ilişkili gen ekspresyonlarındaki farklılıkları incelemek. Gereç ve Yöntem: CD44yüksek/CD24yüksek yüzey belirteçleri pozitif olan MCF-7 meme kanseri hücre hattından KKH’ler akış sitometri metodu ile izole edilmiştir. ZA tedavisi uygulanmış ve uygulanmamış olan KKH gruplarının toplam RNA izolasyonu için cDNA sentezlenmiştir. Son olarak 41 adet otofaji için başlıca ilişkili olabilecek genlerin ekspresyon seviyeleri qRT-PCR analizi ile incelenmiştir. Bulgular: ZA tedavisi uygulanan grup tedavi uygulanmayan grup ile karşılaştırıldığında TGM2, TNF, HSPA8 genlerinin azalmış regüle olduğu ve HSP90AA1 geninin artmış regüle olduğu görülmüştür. Sonuç: Otofaji ile ilişkili genlerin ekspresyon profillerinde ZA tedavisi uygulanan ve uygulanmayan gruplar arasında anlamlı farklar bulunmuştur. Bu bulgular, KKH’lerine karşı hedef olabilecek daha etkili tedavi ajanları geliştirilebilmesi için önemli katkılar sağlayabilir., Aim: In this study we examined differences in the expression of genes associated with autophagy and CSCs for the treatment ZA applied via taking breast cancer stem cells as models. Materials and Methods: CSCs with CD44high/CD24high surface markers have been isolated from the MCF-7 breast cancer cell line with flow cytometry methods. cDNA was synthesized for ZA treatment applied and not applied CSC group with total RNA isolation. Then, 41 essential autophagy-related gene expression levels were analyzed by qRTPCR array analysis. Results: When ZA treatment administrated group compared with non-treatment group, downregulation of TGM2, TNF, HSPA8 and upregulation of HSP90AA1 was detected. Conclusion: There are differences of expression profiles of genes related to autophagy between ZA treated and non-ZA tread group. These findings may provide important information towards us to target CSCs to develop more effective treatments.

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 8 weeks. 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.

The aim of our study is to investigate the effect of sunitinib on diabetes mellitus related-ovarian injury and fibrosis in rat models. An experimental diabetes mellitus model was created in 16 rats, and eight rats with normal blood glucose levels were included in control group (Group-1). The diabetic rats were divided into two groups:diabetic control group (water given) - Group-2 and sunitinib treatment group - Group-3. After four weeks, bilateral oophorectomy was performed and ovaries were examined histologically. The groups were compared by Student's t-test, analysis of variance (ANOVA) and Mann-Whitney's U-test. There was a significant increase in no-medication (water given) diabetic rat's ovary (Group-2) in terms of follicular degeneration, stromal degeneration, stromal fibrosis and NF-kappaB immune-expression compared with control group normal rats' ovary (Group-1) (p 0.0001). Stromal degeneration (p = 0.04), stromal fibrosis (p = 0.01), follicular degeneration (p = 0.02), NF-kappaB immune-expression (p = 0.001) significantly decreased in sunitinib-treated diabetic rat's ovary (Group-3) when compared with no-medication (water given) diabetic rat's ovary (Group-2) (p 0.05). When we used sunitinib in the treatment of diabetic rats, ovarian injury, fibrosis and NF-kappaB immunoexpression decreased significantly. The effects of sunitinib in rat models give hope to the improved treatment of premature ovarian failure due to diabetes mellitus in humans.

WOS: 000348753800012, PubMed ID: 25510691, Objective: The aim of the present study was to investigate the effects of diabetes mellitus (DM) on ovarian reserve and injury by considering laboratory and histopathological parameters in rat models. Materials and methods: An experimental DM model was created in 16 rats. Eight rats with normal blood glucose levels were included in the control group. Diabetic rats were divided randomly into two groups: nontreated and resveratrol-treated groups. Histopathological examination and nuclear factor (NF)-kappa B immunoexpression level determination were performed. Plasma malondialdehyde, glutathione, pentraxin-3, and anti-Mullerian hormone levels were measured. Relations between the variables were compared by Student t test, analysis of variance, and Mann-Whitney U and X-2 tests. Results: We found statistically significantly lower glutathione and anti-Mullerian hormone levels, and higher malondialdehyde and pentraxin-3 levels in nontreated diabetic group when compared with the control and resveratrol-treated diabetic groups. Stromal degeneration, follicle degeneration. stromal fibrosis scores, and NF-kappa B immunoexpression levels were significantly higher in nontreated diabetic rats. Primordial and primary follicle counts were significantly lower in the nontreated diabetic group when compared with the control and resveratrol-treated groups. There was no statistically significant difference in secondary and tertiary follicles between these groups. Conclusion: These findings provide strong evidence that the ovarian follicle pool in nontreated diabetic rats is affected in the early stages of the follicle development process. We precluded negative effects of DM on ovaries by inhibiting the NF-kappa B pathway with resveratrol. We thought that the NF-kappa B pathway plays a role in the pathophysiology of ovarian failure in diabetic rats. Further studies should evaluate this precise mechanism that leads to a decline in the anti-Mullerian hormone levels. In addition, the relationship between this abnormality and reproductive function in diabetic patients should be analyzed further. Copyright (C) 2014, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.

The aim of the present study was to evaluate the effect of sunitinib on endometriotic implants and adhesions in a rat endometriosis model. An experimental endometriosis model was created in 21 rats. These rats were randomly divided into three groups: Group 1 (control group, 7 rats) was given no medication; Group 2 (sunitinib group, 7 rats) was given 3 mg/kg per day of oral sunitinib; and Group 3 (danazol group, 7 rats) was given 7.2 mg/kg per day of oral danazol. The volume of endometriotic implants was calculated. The extent and severity of adhesions were evaluated. The groups were compared by the Student's t-test, analysis of variance (ANOVA) and the Mann-Whitney U test. There was no statistically significant difference in the mean volume of endometriotic implants before medication between three groups. The volume of implants and extent, severity, total score of adhesions were significantly decreased after medication in Group 2 and Group 3. We noted that the volume of the endometriotic implants and adhesion formation were decreased both after sunitinib and danazol treatment. As a result, sunitinib seems to be effective for endometriotic peritoneal lesions. The effects of sunitinib in rat models give hope for improving the treatment of human endometriosis and prevention of pain symptoms.

Diabetic nephropathy is one of the most serious complications of diabetes and the major cause of end-stage renal failure. Consequences of diabetic nephropathy include increased kidney size and glomerular volume, thickening of basement membranes and progressive accumulation of extracellular matrix. Reports in the literature support an association between increased secretion of inflammatory molecules, such as cytokines, growth factors and metalloproteinases, and development of diabetic nephropathy. We investigated the potential of granulocyte colony- stimulating factor (G-CSF) as a therapeutic candidate for preventing diabetic nephropathy. We used 21 8-week-old male rats; 14 were administered a single dose of 60 mg/kg streptozotocin (STZ) to induce diabetes. The rats were divided into three groups of seven: group 1, control; group 2, diabetic; group 3, diabetic plus G-CSF treatment. After 4 weeks, immunoexpressions of transforming growth factor β1 (TGF-β1), Akt and CD34 levels were measured in the kidney tissue. Blood glucose, urine protein and the glomerular area also were measured for each group. We found that G-CSF treatment decreased TGF-β1 immunoexpression, urine protein and glomerular area in kidneys of diabetic rats, and increased CD 34 and Akt immunoexpression in kidneys of diabetic rats. The effects of G-CSF were independent of blood glucose levels. G-CSF may be a useful therapeutic agent for preventing diabetic nephropathy.

To investigate the efficacy of montelukast for prevention of ischaemia/reperfusion (I/R) injury in rat ovary.Twenty-four female adult rats were included in the study. I/R injury was induced by CO2 pneumoperitoneum in a laparoscopic rat model. The rats were divided at random into three groups: the sham group was subjected to catheter insertion but was not subjected to pneumoperitoneum; the saline group was subjected to 60 min of pneumoperitoneum and 30 min of reperfusion, with 1 mg/kg physiological saline administered 10 min before pneumoperitoneum; and the montelukast group was subjected to 60 min of pneumoperitoneum and 30 min of reperfusion, with 20mg/kg montelukast administered 10 min before pneumoperitoneum. Damage to ovarian tissue was scored by histopathological evaluation. Caspase-3 expression was determined immunohistochemically. Ovarian tissue levels of malondialdehyde and glutathione, and plasma total antioxidant capacity were measured biochemically.In comparison with the sham group, ovarian sections in the montelukast group had higher scores for follicular degeneration and oedema (p0.001). Montelukast treatment prevented tissue damage in ovaries, and this result was significant. Caspase-3 expression was only observed in ovarian surface epithelium in the saline and montelukast groups. However, the mean caspase-3 expression score was higher in the saline group than the montelukast group (p0.001). Tissue levels of malondialdehyde were higher in the montelukast group than the sham group, but plasma total antioxidant capacity and tissue levels of glutathione were significantly lower. Pretreatment with montelukast reduced lipid peroxidation (p0.005) and improved antioxidant status in rats (p0.001).Montelukast is effective for the prevention of I/R-induced damage in rat ovary.

Amaç: Kanser kök hücreler (KKH) ile kötü prognoz, metastaz ve rekürens arasında güçlü bir ilişki vardır. Buna ek olarak KKH'ler kemoterapi ve radyoterapiye dirençli hücrelerdir. Bu nedenle mevcut tedavi yaklaşımları KKH'lerin eliminasyonunda yetersiz kalabilmektedir. Tümör hücrelerinin immün hücrelerden kaçabilmek için çeşitli adaptasyonları bulunur. Ekspresyonları fetal dokularla kısıtlı olan human leukocyte antigen (HLA) G ve ayrıca HLA-E, tümör immün evazif adaptasyonlardır. Bu çalışmada meme tümörlerinde KKH ve immün evazif adaptasyonlar arasındaki ilişkiyi incelemeyi amaçladık. Yöntemler: İleri evre meme kanseri dokuları (n=10) ile malign olmayan meme tümörü dokularında (n=10) immünohistokimyasal olarak cluster of differentiation (CD)44, CD133, Homeobox protein Nanog, octamer-binding transcription factor (Oct)3/4, HLA-G ve HLA-E ekspresyonlarını değerlendirdik. Bulgular: Özellikle Nanog (p, Objective: There is a strong relationship between the cancer stem cells (CSCs) and poor prognosis, metastasis and recurrence. In addition to this CSCs are resistant to chemotherapy and radiotherapy. Therefore, current treatment approaches may be ineffective to elimination of CSCs. The tumor cells have various adaptations for escaping from immune cells. The human leukocyte antigen (HLA) -G, which expressions restricted with fetal tissues and HLA-E are kind of tumor immune evasive adaptations. In this study, we aimed to investigate the relationship between the CSCs and immune evasive adaptations of breast tumors. Methods: We immunohistochemically evaluated that the expressions of cluster of differentiation (CD) 44, CD133, Homeobox protein Nanog, octamerbinding transcription factor (Oct) 3/4, HLA-G and HLA-E in the advanced stage breast cancer tissues (n=10) and the non-malignant breast biopsies (n=10). Results: We detected that the significantly increased expressions of especially Nanog (p

Amaç: Tirozin kinaz inhibisyonunun diyabet etkisi altındaki testis dokusu üzerine göstereceği etkileri araştırmaktır. Gereç ve Yöntem: Çalışmamızda 31 adet CD1 türü erkek fare kullanıldı ve dört gruba ayrıldı: Grup 1'de (kontrol grubu) 7, Grup 2'de tirozin kinaz inhibitörü uygulanan 7, Grup 3'te diyabetik ve SF uygulanan 8, Grup 4'te diyabet + tirozin kinaz inhibitörü uygulanan 9 denek hayvanı yer aldı. Grup 1'de herhangi bir uygulama yapılmadı. Grup 2'deki farelere 3 hafta boyunca tirozin kinaz inhibitörü verildi. Diyabet oluşturulması için 0.1mol/L tek doz streptozotosinin intraperitoneal olarak verildi. 250 mg/dL ve üzeri kan glikoz seviyesi diyabetik olarak kabul edildi. Deneysel diyabet modeli oluşturulan farelere 1 hafta beklendikten sonra, Grup 3'e SF, Grup 4'e 3 hafta boyunca tirozin kinaz inhibitörü verildi. Sonunda tüm denek hayvanları anestezi altında sakrifiye edilerek histopatolojik inceleme için testis dokuları alındı. İstatistiksel analiz için tek yönlü varyans analizi (ANOVA) testi yapıldı, 0.05'ten küçük p değerleri, istatistiksel olarak anlamlı kabul edildi. Bulgular: Testis dokusu histopatolojik olarak incelendiğinde deneysel diyabete bağlı olarak seminifer tübülün germ hücre serilerinde kayıp, hücre bütünlüklerinde ise bozulma saptandı. Sonuç: Bu çalışma, diyabetin testiste germ hücre serilerinde sayısal olarak azalmaya ve hücre adezyon mekanizmasında bozulmaya yol açtığını göstermektedir. Tirozin kinaz inhibitörü uygulamasının, bu hasarlanmada tamir edici etkisinin olduğu düşünülmektedir. Bu hasarın tedavisinin derecesi, uygulanan tirozin kinaz inhibitörünün dozu ve süresine bağlı olarak farklılık gösterebilmektedir. Ancak, klinik diyabet uygulamalarında tirozin kinaz inhibitörü kullanılabilmesi için bu konuda moleküler çalışma sayılarının artışına ihtiyaç vardır., Aim: The aim of the study is to investigate the effects of tyrosine kinase inhibition on testicular tissue under the effects of diabetes mellitus. Materials and Methods:. Thirty one CD-1 male mice were divided into four groups: Group 1 (control group) consited 7, Group 2 (tyrosine kinase inhibitor given group) 7, Group 3 (diabetic group treated with SF) 8 and Group 4 (diabetic group treated with tyrosine kinase inhibitor) 9 experimental mice. No application was made to the animals in Group 1. In Group 2, mice were given tyrosine kinase inhibitor for 3 weeks. Diabetes was induced by intraperitoneal injection of single dose of streptozotocin 0.1mol/L. Mice with 250 mg/dL and higher blood glucose levels were accepted as diabetic. After waiting for 1 week, experimental diabetic mice in Group 3 were treated with SF and those in Group 4 were treated with tyrosine kinase inhibitor for 3 weeks. Then, all the experimental animals were sacrified and the testicular tissue was removed for histopathological examination.The one-way analysis of variance (ANOVA) is used for statistical analysis, a p value less than 0.05 was considered statistically significant. Results: Histopathologic examination of the testes revealed loss of germ cells series in the seminiferous tubules and deterioration in cellular integrity depending on experimental diabetes. Conclusion: By the study, it was demonstrated that diabetes lead to a decrease in the number of germ cells in testes and deterioration in cell adhesion mechanism. The administration of tyrosine kinase inhibitor could be considered to have a regenerative effect in this damage. The degree of treatment of this injury varies depending to the dose and time of the tyrosine kinase inhibitors. But, for the use of tyrosine kinase inhibitors in clinical practice of diabetes mellitus, more molecular studies are needed.

WOS: 000416401500005, PubMed ID: 28994095, Introduction. Sunitinib is an oral inhibitor of vascular endothelial growth factor that is used to treat a variety of cancer. There are limited data regarding the effect of sunitinib on diabetes. In the liver, Notch signaling plays an important role in liver tissue development and homeostasis and its dysfunction is associated with liver pathologies. The aim of the present study is to investigate the effects of sunitinib on streptozotocin (STZ)-induced diabetic liver in mice models. Material and methods. An experimental diabetes mellitus (DM) model was created in 28 male CD-1 mice. Twenty-eight male CD-1 mice divided in four groups (n = 7 each) were used; control mice (C), control mice treated with sunitinib (C + S), diabetic mice (DM), and diabetic mice treated with sunitinib (DM + S) for four weeks. The histopathological changes in the liver were examined by histochemistry and immunohistochemistry. Immunoreactivity of Notch1, Jagged1, DLL-1 and VEGF were evaluated in control and diabetic mice after sunitinib treatment. Results. The significant morphological changes in the liver were mostly seen in hepatocytes that were hypertrophied in the DM mice, with an increased amount of eosinophilic granules; moreover, some hepatocytes contained empty vacuole-like structures. The livers of the DM mice revealed increased deposition of collagen fibers. After sunitinib treatment the hepatocytes and hepatic lobules had almost similar morphology to control mice. The immunoreactivities of Notch1, Jagged1, DLL-1 and VEGF in hepatocytes were significantly lower in the DM group when compared with the C, DM + S and C + S group treated with sunitinib. Conclusions. These results suggest that sunitinib effectively protects the liver from diabetes-induced damage through the inhibition of the Notch pathway.

Aim: The aim of this study was to investigate whether prophylactic treatment with edaravone prevents ischemia/reperfusion (I/R)-induced ovarian damage during pneumoperitoneum in an experimental rat model. Methods: Twenty-eight female Sprague Dawley rats were allocated randomly to 4 groups. The sham group (group 1) was only subjected to catheter insertion, not to pneumoperitoneum. Group 2 received a 1 mg/kg dose of 0.9% sodium chloride by the intraperitoneal route for 10 min before pneumoperitoneum. Groups 3 and 4 received 6 and 12 mg/kg edaravone, respectively, by the intraperitoneal route for 10 min before pneumoperitoneum. After 60 min of pneumoperitoneum, the gas was deflated. Immediately after the reperfusion period, both ovaries were excised for histological scoring, caspase-3 immunohistochemistry and biochemical evaluation including glutathione (GSH) and malondialdehyde (MDA) levels. Also, total antioxidant capacity (TAC) was measured in plasma samples to evaluate the antioxidant effect of edaravone. Results: Ovarian sections in the saline group revealed higher scores for follicular degeneration and edema (p < 0.0001) when compared with the sham group. Administration of different doses of edaravone in rats significantly prevented degenerative changes in the ovary (p < 0.0001). Caspase-3 expression was only detected in the ovarian surface epithelium in all groups, and there was a significant difference between the treatment groups and the saline group (p < 0.0001). Treatment of rats with edaravone reduced caspase-3 expression in a dose-dependent manner. Moreover, biochemical measurements of oxidative stress markers (MDA, GSH and TAC) revealed that prophylactic edaravone treatment attenuated oxidative stress induced by I/R injury. Conclusion: These results indicate that prophylactic treatment with edaravone prevents I/R-induced ovarian damage during pneumoperitoneum in an experimental rat model.

WOS: 000318652100001, PubMed ID: 23671879, The aim of this study was to investigate the effects of experimentally induced diabetes on (a) germ cells, (b) in vitro fertilization (IVF) success rate, and (c) gap junction and cell adhesion molecule gene and protein expressions during the early blastocyst period. Germ cells were obtained from healthy and diabetic rats, analyzed for number, motility, and morphology, and used for IVF. After reaching the early blastocyst stage, the expressions of genes encoding gap junction proteins and cell adhesion molecules were analyzed by quantitative RT-PCR. Histomorphologically and immunohistochemically analyses were also performed. Diabetes significantly affected sperm number and motility and the development of oocytes. Gene expressions of beta-catenin and connexin family members and protein expressions of E-cadherin and connexin-43 significantly decreased in groups including germ cells isolated from diabetic rats. Connective tissue growth factor expression increased in groups that included sperm cells isolated from diabetic male rats, whereas mucin-1 expression increased in the group that included oocytes isolated from diabetic female rats paired with sperm cells isolated from healthy male rats. In summary, experimentally induced diabetes was found to influence gap junctions, cell adhesion molecules, and associated proteins which all have important roles in germ cell maturation, fertilization, and development., Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TUBITAK 109S457], This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK 109S457 to H. Aktug).

Similarities and differences in the cell cycle components, apoptosis and cytoskeleton-related molecules among mouse skin fibroblast cells (MSFs), mouse squamous cell lung carcinomas (SqCLCs) and mouse embryonic stem cells (mESCs) are important determinants of the behaviour and differentiation capacity of these cells. To reveal apoptotic pathways and to examine the distribution and the role of cell cycle-cell skeleton comparatively would necessitate tumour biology and stem cell biology to be assessed together in terms of oncogenesis and embryogenesis. The primary objectives of this study are to investigate the effects of flavopiridol, a cell cycle inhibitor, and geldanamycin, a heat shock protein inhibitor on mouse somatic, tumour and embryonic stem cells, by specifically focusing on alterations in cytoskeletal proteins, cell polarity and motility as well as cell cycle regulators. To meet these objectives, expression of several genes, cell cycle analysis and immunofluorescence staining of intracellular cytoskeletal molecules were performed in untreated and flavopiridol- or geldanamycin-treated cell lines. Cytotoxicity assays showed that SqCLCs are more sensitive to flavopiridol than MSFs and mESCs. Keratin-9 and keratin-2 expressions increased dramatically whereas cell cycle regulatory genes decreased significantly in the flavopiridol-treated MSFs. Flavopiridol-treated SqCLCs displayed a slight increase in several cell cytoskeleton regulatory genes as well as cell cycle regulatory genes. However, gene expression profiles of mESCs were not affected after flavopiridol treatment except the Cdc2a. Cytotoxic concentrations of geldanamycin were close to each other for all cell lines. Cdkn1a was the most increased gene in the geldanamycin-treated MSFs. However, expression levels of cell cytoskeleton-associated genes were increased dramatically in the geldanamycin-treated SqCLCs. Our results revealing differences in molecular mechanisms between embryogenesis and carcinogenesis may prove crucial in developing novel therapeutics that specifically target cancer cells.

Marine bivalve mussels, especially Mytilus species are an earlywarning system used for determining of damage caused by the various aquatic pollutions. In the present study, Mytilus galloprovincialis L. (black mussel) have been utilised as a biomonitoring organism to reveal environmental pollution in the Aliaga, Foca and Urla where located along the Izmir Coast of Turkey. Mussels were collected at these areas and gill and hepatopancreas (digestive gland) tissues were excised. mRNA expressions of initiator (caspase-2 and -8) and executioner (caspase -3/7-1, -3/7-2, -3/7-3 and -3/7-4) caspases of mussels tissues in areas exposed to pollution agent have been observed. TUNEL immunoreactivity in paralel to histopathological changes in both Aliaga and Foca areas were compared with Urla. This study is the first report to reveal the pollution with apoptotic expression on mussels in the coast of Turkey.

PubMed ID: 27787370, Background: Flavopiridol a semisynthetic flavone that inhibits cyclin-dependent kinases (CDKs) and has growth-inhibitory activity and induces a blockade of cell-cycle progression at G1-phase and apoptosis in numerous human tumor cell lines and is currently under investigation in phase II clinical trials. Cancer stem cells (CSCs) are comprised of subpopulation of cells in tumors that have been proposed to be responsible for recurrence and resistance to chemotherapy. The aim of the present study was to investigate the effects of flavopiridol in cancer stem cell cytoskeleton, cell adhesion, and epithelial to mesenchymal transition in CSCs. Methods:The cells were treated with flavopiridol to determine the inhibitory effect. Cell viability and proliferation were determined by using the WST-1 assay. Caspase activity and immunofluorescence analyses were performed for the evaluation of apoptosis, cell cytoskeleton, and epithelial-mesenchymal transition (EMT) markers. The effects of flavopiridol on the cell cycle were also evaluated. Flow cytometric analysis was used to detect the percentages of CSCs subpopulation. We analyzed the gene expression patterns to predict cell cycle and cell cytoskeleton in CSCs by RT-PCR. Results: Flavopiridol-induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspases activity. Cell cycle analyses revealed that flavopiridol induces G1 phase cell cycle arrest. Flavopiridol significantly decreased the mRNA expressions of the genes that regulate the cell cytoskeleton and cell cycle components and cell motility in CSCs. Conclusion: Our results suggest that Flavopiridol has activity against lung CSCs and may be effective chemotherapeutic molecule for lung cancer treatment. © Copyright 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.

JAK/STAT is an evolutionarily conserved pathway and very important for second messenger system. This pathway is important in malignant transformation and accumulated evidence indicates that this pathway is involved in tumorigenesis and progression of several cancers. It was possible to assume that activation of JAK/STAT pathway is associated with increase in the expressions of ICAM/1 and VCAM-1. In this study we hypothesized that when cells were maintained as spheroids or monolayers, the structure of cancer stem cells (CSCs) could show differentiation when compared with non-CSCs.DU-145 human prostate cancer cells were cultured using the Ege University molecular embryology laboratory medium supplemented wıth 10% fetal bovine serum. Clusters of differentiation 133 (CD133)(+high)/CD44(+high) prostate CSCs were isolated from the DU145 cell line by using BD FACSAria. CD133//CD44+ CSCs were cultured until confluent with 3% noble agar. The expression of these proteins in CSCs and non-CSCs was analyzed by immunohistochemistry.Different expression profiles were observed in the conventional two-dimensional (2D) and three-dimensional (3D) experimental model system when CSCs and non-CSCs were compared. Human prostate CSCs exhibited intense ICAM-1 and VCAM-1 immunoreaction when compared with non-CSCs. These findings were supported by the fact that VCAM-1 on the surface of cancer cells binds to its counterreceptor, the α4β1 integrin (also known as very-late antigen, VLA-4), on metastasis-associated macrophages, triggering VCAM-1-mediated activation of the phosphoinositide 3-kinase growth and survival pathway in cancer cells.The results of this study showed that changes in JAK/STAT pathway are related with adhesion molecules and could affect cancer progression.

PubMed ID: 26466786, Background: Growth factors such as nerve growth factor (NGF) and insulin-like growth factor-1 (IGF-1) have been shown to play a role in the healing process of nerve injury. Recent researches have also shown that oxytocin administration activates these growth factors of importance for the healing of nerve tissue. The objective of the present study was to evaluate the effects of oxytocin on peripheral nerve regeneration in rats. Methods: Twenty-four male Sprague-Dawley rats were underwent transection damage model on the right sciatic nerve and defective damage model on the left sciatic nerve. The animals were assigned to one of two groups: control group or treatment group (received 80mg/kg oxytocin intraperitoneally for 12weeks). The sciatic nerve was examined, both functionally (on the basis of climbing platform test) and histologically (on the basis of axon count), 3, 6, 9, and 12weeks after the injury. Also, stereomicroscopic and electrophysiological evaluations were carried out. Results: Significantly greater improvements in electrophysiological recordings and improved functional outcome measures were presented in the treatment group at 12-week follow-up. Stereomicroscopic examinations disclosed prominent increases in vascularization on proximal cut edges in the oxytocin group in comparison with the control group. Higher axon counts were also found in this group. Conclusion: Intraperitoneal oxytocin administration resulted in accelerated functional, histological, and electrophysiological recovery after different sciatic injury models in rats. © 2015 Gümüs et al.

To examine and compare the neuroprotective effects of dexamethasone, oxytocin, and resveratrol administration on regeneration after facial nerve crush injury in a rat model.Prospective, randomized, controlled animal study.A crush-type facial nerve injury was performed on the right side of all rats (injury group [IG]), whereas there was no injury on the left side (sham group [SG]). These main groups were divided into five subgroups: 1) no medicine (control); 2) physiological serum; 3) dexamethasone; 4) oxytocin; and 5) resveratrol (Res) administered (intraperitoneal injection) for 28 days. Functional recovery was evaluated by daily eye-blink reflex and facial electromyography. Nerve-muscle degeneration and regeneration, apoptosis, and intercellular connections were evaluated in histopathological and immunohistochemical examinations.Recovery time of the postinjury eye-blink reflex demonstrated faster recovery in IG+Res when compared with the other subgroups. In peak-to-peak amplitude values, a significant increase was observed in the dexamethasone (P=0.007) and oxytocin subgroups (P=0.004) and was even more apparent in the resveratrol subgroup (P0.001). Nerve regeneration is apparent in the resveratrol subgroup. Apoptotic changes were evaluated immunohistochemically with TUNEL and Caspase 3 and 6 antibodies staining. Caspase 3 and 6 immunoexpressions of resveratrol and oxytocin subgroups were moderate when compared with dexamethasone subgroup. Except for the resveratrol subgroup, which had an increase in expression, the majority of subgroups were similar to SG in terms of intercellular connections (Connexin 32 and 43).Resveratrol leads to the best outcome after facial nerve crush injury in rats when compared with dexamethasone and oxytocin, even though these agents demonstrate a significant improvement in facial nerve regeneration.N/A.

Mesenchymal stem cells (MSCs) represent a new approach to the treatment of several neoplastic or non-neoplastic disorders. Their potential to repair damaged tissues through trans differentiation in conjunction with their immunomodulatory ability made them promising candidates for cell-based immunotherapy and regenerative medicine. In the present study, we aimed to determine the effects of MSCs on proliferation, apoptosis and gene expression profile of the acute lymphoblastic leukemia (ALL) cell line CCRF-CEM.The experiments were performed after MSCs and CCRF-CEM cells were co-cultured for 72 hrs. We analyzed the gene expression patterns to predict oncogenic pathway dysregulation in the cell groups by quantitative RT-PCR and immunohistochemical staining.Cell proliferation was significantly inhibited in co-cultured CCRF-CEM cells compared to the control. Furthermore, growth factors, p53, Bax and Caspase-9 expressions were increased and cell-signaling gene expressions decreased significantly. Despite increased levels of growth factors (CTGF, VEGF, FGF, EGFR), the increased apoptosis level was triggered by p53/ Bax.In this study we have shown that human MSCs have inhibitory effect on their neighboring malignant leukemia cells.

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 µg/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.

Capsaicin, an ingredient of red chili pepper, has possible tumorigenicity/genotoxicity properties. We aimed to determine the effects of capsaicin on the proliferation and gene expression profiles of acute lymphoblastic leukemia (ALL) CCRF-CEM cell line.Cell viability and IC50 dose was determined by WST cytotoxicity assay. qRT-PCR, immunohistochemical staining and western blot methods were used to determine target genes' expression levels. Apoptosis was evaluated by measuring the caspase-3 activity.Capsaicin inhibited the proliferation of CCRFCEM cells in a dose-dependent manner. Increased mRNA expressions of caspase gene family members, activated caspase-3 and decreased mRNA and protein expression of BCL-2 gene indicated apoptotic response to capsaicin. Moreover capsaicin treatment suppressed significantly the expression of the key cell signaling pathways of KRAS, AKT, GAB2, PTPN11, BRAF, INPP5D, MAPK7.Capsaicin induces apoptosis in CCRF-CEM cells and this response is associated with downregulation of cell signaling pathways.