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One of the most dangerous gynecological emergencies is ovarian ischemia that commonly occurs during surgical manipulation or presence of ovarian masses.finding new therapies to prevent the associated harmful effects of ischemia/reperfusion-induced damage is still a critical need. For the first time, we aimed to evaluate the possible role of phosphodiesterase (PDE) 3 A inhibitor (PDEI), cilostazol (CLZ) in the treatment of ovarian ischemia reperfusion induced damage (OIR).Rats were divided into five groups; sham, OIR group; CLZ (5, 10, 20 mg/kg) was given orally with induced OIR. Different biochemical parameters were detected such as total anti-oxidant capacity (TAC), reduced glutathione (GSH), malondialdehyde (MDA), cyclic adenosine monophosphate (cAMP), sirtuin1 (SIRT1), toll like receptor 4 (TLR4), nuclear factor kappa b (NF-κB) and tumor necrosis factor alpha (TNFα). In addition, histopathological features, ovarian weight changes and casapse3 immunoexpression were detected.Data revealed significant increase in ovarian weight changes, MDA, TLR4, TNFα, NF-κB and caspase 3 expressions in OIR induced group. Moreover, OIR group had histopathological features of ovarian damage with depletion of cAMP, SIRT1, TAC and GSH.CLZ could ameliorate OIR-induced damage due to PDE inhibition, anti-oxidant, anti-inflammatory and anti-apoptotic properties with modulation of TLR4/NF-κB/TNFα and cAMP/SIRT1 signaling pathways.

50 male Wistar albino rats were subjected to DOX toxicity via administration of singleOur data revealed that VIN succeeded in protecting the heart against DOX induced damage as manifested by significant decrease of cardiac enzymes, hypoxia inducible factor alpha (HIF-1α), vascular endothelial growth factor-A (VEGF-A), tissue malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α) and caspase3 levels. Furthermore, VIN given group showed marked improvement of the histopathological changes of cardiac injury, total antioxidant capacity (TAC), elevation of reduced glutathione (GSH), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP) and sirtuin-1 (SIRT-1).We concluded that VIN could ameliorate DOX induced cardiac damage and this effect may be attributed to modulation of HIF/VEGF signaling pathway, up-regulation of cGMP/cAMP/SIRT pathway, inhibition of phosphodiesterase enzyme, besides its anti-apoptotic, anti-inflammatory, and anti-oxidant properties.

Placenta accreta (PA) can be life-threatening due to postpartum hemorrhage and may lead to cesarean hysterectomy. We investigated the expression of Matrix metalloproteinase-2 (MMP-2), β-catenin, E-...

Clear cell renal cell carcinoma (ccRCC) has an unpredictable clinical consequence even with the use of usual prognostic factors. To determine whether utilization of cell proliferation and cell adhesion by using MCM2 and CD44 immuno-expression could predict the biological performance of ccRCC. MCM2 and CD44 protein expression levels in tumor tissues from 120 ccRCC patients were evaluated by immunohistochemistry. The relationships between MCM2 and CD44 expression and clinicopathological parameters were evaluated. The overall survival (OS) was computed by the Kaplan-Meier method. The role of MCM2 and CD44 in the prognosis was estimated by univariate and multivariate Cox regressions. The results showed high MCM2 and CD44 protein expression levels in 63.3% and 55% of ccRCC cases, respectively. MCM2 and CD44 over-expression was significantly related to tumor grade (p = 0.001 and p = 0.003, respectively), T stage (p = 0.005 and p = 0.008, respectively), lymph node status (p = 0.015 and p = 0.040, respectively), AJCC stage (p = 0.000 and p = 0.002, respectively) and OS (p = 0.019 and p = 0.001, respectively). Multivariate Cox regression showed that high MCM2 and CD44 expression levels were independently associated with prognosis of ccRCC cases (HR = 2.687, 2.810, 95% CI: 1.217-5.920, 1.267- 6.233, respectively). MCM2 and CD44 are considered as independent risk and poor prognostic factors for the prognosis of ccRCC patients.

Cyclophosphamide (CP) is a widely used chemotherapeutic agent but its clinical usefulness is challenged with different forms of toxicities. No studies have evaluated the possible protective effect of nicorandil (NIC) in CP-induced cardiotoxicity. Our study aimed to investigate this effect by using NIC (3 mg/kg/day) orally for 5 days, in the presence or absence of cardiotoxicity induced by intraperitoneal (i.p.) injection of CP (150 mg/kg) on 4th and 5th days. We confirmed the role of ATP-sensitive potassium channel (KATP) by coadministration of glibenclamide (GP) (5 mg/kg/day) 2 h before NIC (3 mg/kg/day) for 5 days. Moreover, the role of endothelial nitric oxide synthase (eNOS) was confirmed by coadministration of nitro-ω-l-arginine (l-NNA) (25 mg/kg/day) for 5 days. Results showed that CP succeeded in induction of cardiotoxicity which manifested by a significant increase in heart weights, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin I, cardiac tissue malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL1 β), and caspase-3 levels. Furthermore, CP group showed toxic histopathological changes of marked cardiac damage in addition to a significant decrease in total antioxidant capacity (TAC), superoxide dismutase (SOD), eNOS gene expression, and B cell lymphoma 2 (Bcl2) immunoexpression. NIC succeeded in reversing CP-induced cardiotoxicity by its potassium channel opening effect, stimulating eNOS gene expression, anti-inflammatory, antiapoptotic, and antioxidant properties. Coadministration of GP or l-NNA could diminish the protective effect of NIC. This proves the important role of KATP and eNOS in mediating such protection.

Polycystic ovary syndrome (PCOS) is a very common gynecological disease during childbearing period and markedly affects female fertility. Until now, there are no studies evaluating the possible curative effect of diacerein (DIA) in induced PCOS. For the first time, we aimed in current model to study the effect of DIA (50 mg/kg/day) orally for 3 weeks on experimentally induced PCOS by letrozole (1 mg/kg/day) for 3 weeks. We measured rats' body weight changes, levels of serum insulin, anti-Müllerian hormone (AMH), testosterone, inflammasome, caspase1, and total anti-oxidant capacity (TAC). Moreover, we measured ovarian tissue parameters as malondialdehyde (MDA), interleukin 1β (IL1β), real-time polymerase chain reaction (rt-PCR) of Bcl2-associated X protein (Bax), and interleukin 10 (IL10) gene expression changes. Furthermore, histopathological features and anti-apoptotic marker B cell lymphoma 2 (Bcl2) immunoexpression changes were evaluated. Our results showed that letrozole markedly induced PCOS as manifested by significant increase in serum testosterone, insulin, AMH, rats' body weights, ovarian tissue MDA, IL1β, inflammasome, and caspase1 but decrease of serum TAC. In addition, gene expression of Bax increased but IL10 gene expression decreased. Ovaries showed the typical histopathological changes of PCOS with no immunoexpression of Bcl2. DIA was greatly able to ameliorate letrozole-induced PCOS changes in rats mainly via prevention of IL1β, and improving metabolic disturbances, and its anti-apoptotic, anti-oxidant, and anti-inflammatory effects with further regulation of inflammasome/caspase1/IL1β and Bax/Bcl2 pathways.

Placenta accreta (PA) can be life-threatening due to postpartum hemorrhage and may lead to cesarean hysterectomy. We investigated the expression of Matrix metalloproteinase-2 (MMP-2), β-catenin, E-cadherin (E-CAD), transforming growth factor β1 (TGF-β1), glutathione peroxidase 1 (GPx-1), reduced glutathione (GSH) and superoxide dismutase (SOD) in PA compared to controls to determine if alterations may contribute to PA. Materials and methods: Twenty six PA and 31 controls were evaluated immunohistochemically for expression of MMP-2, β-catenin and E-CAD on villous and extravillous trophoblasts. TGF-β1 and GPx-1 mRNA levels were evaluated by rt-PCR. We measured biochemical levels of GSH and SOD. Results: Significant increases of MMP-2 immunoexpression, GPx-1 mRNA, SOD and GSH levels, decreases in immunoexpression of E-CAD and β-catenin and TGF-β1 mRNA were found in PA. Conclusion: These findings suggest that loss of cell-cell adhesion and increased antioxidants level may have a role in PA.

Drug-induced cardiotoxicity is a serious adverse effect that occurs during the administration of chemotherapeutic agents such as cyclophosphamide (CYC). Therefore, there is a critical need to find cardioprotective agents to keep the heart healthy. The current study aimed to investigate the protective effect of simvastatin (SIM) against CYC-induced heart damage and evaluate different mechanisms involved in mediating this effect, including the inflammasome/caspase1/interleukin1β (IL1β) pathway and endothelial nitric oxide synthase (eNOS). 36 rats were randomly assigned to one of four groups: a control group that received only vehicles, a CYC group that received CYC (150 mg/kg/day) i.p. on the fourth and fifth days, a CYC+SIM group that received SIM (10 mg/kg/day) orally for 5 days and CYC (150 mg/kg/day) i.p. on the fourth and fifth days, and a CYC+SIM+ Nitro- ω-L-arginine (L-NNA) group that received L-NNA (25 mg/kg/day, SIM (10 mg/kg/day) orally for 5 days and CYC (150 mg/kg/day) i.p. on the 4th and 5th days. The CYC group revealed an obvious elevation in cardiac enzymes and heart weights with toxic histopathological changes. Moreover, there was an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNFα) levels, and up-regulation of the NLRP3inflammasome/caspase1/IL1β pathway. In addition, total antioxidant capacity (TAC), eNOS, reduced glutathione (GSH), and superoxide dismutase (SOD) significantly decreased. CYC-induced cardiotoxicity was most properly reversed by SIM through its anti-oxidant, anti-inflammatory, and anti-apoptotic actions with the stimulation of eNOS. The co-administration of L-NNA diminished the protective effect of SIM, indicating the essential role of eNOS in mediating this effect. Therefore, SIM ameliorated CYC-induced cardiotoxicity.

Cervical hyperkeratosis is a common gynecological lesion and usually caused by inflammation or trauma. We investigated the effect of Diacerein on Estradiol benzoate-induced cervical hyperkeratosis. Diacerein (50mg/kg/day) was given orally to rats for 4 weeks in the presence or absence of cervical hyperkeratosis induced by intramuscular injection of Estradiol benzoate (60μg/100g) 3 times per week for 4 weeks. We measured the serum levels of total cholesterol, uterine weights, uterine tissue malondialdehyde, total nitrites, superoxide dismutase activity, caspase-3, interleukin-1b immunoexpression and histopathology. Our results showed that Estradiol benzoate succeeded to induce cervical hyperkeratosis which was detected by typical histopathological changes. In addition; there was significant reduction in superoxide dismutase levels and caspase-3 immunoexpression but significant increase in serum total cholesterol, malondialdehyde, total nitrites and interleukin-1b immunoexpression. Diacerein could improve all measured parameters to normal levels. It markedly prevented cervical hyperkeratosis through its anti-inflammatory (IL-1b receptor inhibitor), antioxidant and anti-apoptotic effects.

Cyclophosphamide (CP) is a widely used chemotherapeutic agent but its clinical usefulness is challenged with different forms of toxicities. No studies have evaluated the possible protective effect of nicorandil (NIC) in CP-induced cardiotoxicity. Our study aimed to investigate this effect by using NIC (3 mg/kg/day) orally for 5 days, in the presence or absence of cardiotoxicity induced by intraperitoneal (i.p.) injection of CP (150 mg/kg) on 4th and 5th days. We confirmed the role of ATP-sensitive potassium channel (K

Background Colorectal cancer is one of the most frequent cancers worldwide. Zinc-finger E-box-binding homeobox 2 (ZEB2) is expressed in neoplastic tissues and has emerged as an important regulator of epithelial–mesenchymal transition. Aim The present work was conducted to examine the immunohistochemical expression of ZEB2 in 140 cases of primary colorectal adenocarcinoma and in 52 corresponding metastatic lymph nodes (LNs) to evaluate its expression pattern and to evaluate its association with various clinicopathological features. Results Nuclear ZEB2 high expression was detected in 76 (53.3%) cases of primary colorectal adenocarcinoma. A statistically significant positive association was detected between ZEB2 immunoexpression and tumor grade, tumor-infiltrating lymphocytes, tumor size, LN metastasis, TNM staging, and modified Dukes staging. Regarding expression in the primary tumor and its corresponding metastatic LNs, a statistically significant correlation was observed. The relationship between the prognosis and the expression of ZEB2 in primary colorectal adenocarcinoma cases was evaluated via multivariate Cox regression and stated that positive ZEB2 expressions significantly increased the risk of adverse consequences (hazard risk =2.687, 95% confidence interval: 1.217–5.930, P=0.014, and hazard risk=2.810, 95% confidence interval: 1.267–6.233, P=0.011). Conclusion ZEB2 expression is significantly associated with poor prognostic factors and thus can be used as a prognostic indicator for patients with colorectal adenocarcinoma.

Background Gastric cancer is one of the commonest malignant tumors worldwide. Caveolin-1 (Cav-1) has been involved in variable processes, including migration, cellular transformation, signal transduction, and carcinogenesis. Forkhead box protein A1 (FOXA1) is a transcription factor that regulates chromatin structure and recruits other transcription factors to enhance transcription of downstream molecules. Materials and methods The present work was conducted to study the immunohistochemical expression of Cav-1 and Forkhead box protein A1 (FOXA1) in 60 formalin-fixed paraffin-embedded tissue blocks from gastric adenocarcinoma. Results High nuclear expression of Cav-1 and FOXA1 was detected in 37 (61.7%) cases and 35 (58.3%) cases (61.7% and 58.3%), respectively. A statistically significant relationship was detected between their immunoexpression and tumor grade, lymph node metastasis, TNM stage, and overall survival. Cav-1 and FOXA1 immunoexpression showed a moderate positive correlation in gastric adenocarcinoma. Conclusion Cav-1 and FOXA1 immunoexpression was significantly associated with poor prognostic factors and thus could be used as prognostic indicators for patients with gastric carcinoma.

Ovarian torsion is a dangerous gynecological emergency condition. Early diagnosis of this case is necessary to preserve the function of the ovaries and fallopian tubes and prevent further damage. Ovarian torsion means complete or partial rotation of the adnexa with ischemia followed by reperfusion period. Ovarian torsion affects 2%-15% of patients who have surgical treatment of adnexal masses. We investigated the effect of pioglitazone (PIO) on induced ovarian ischemia reperfusion (OIR). PIO (10, 30 mg/kg) was administered orally in the presence or absence of induced OIR. We measured ovarian tissue malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), heme-oxygenase 1 (HO-1), and gene expressions of peroxisome proliferator activated receptor gamma (PPARγ), tumor necrosis factor alpha (TNFα), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Moreover, expression of p53 and histopathological changes were also evaluated. Results showed increase in the ovarian tissue levels of MDA and NOx and gene expressions of p53, TNFα, and iNOS in the induced OIR group. The induced OIR group showed the histopathological changes associated with cell injury, marked ovarian edema, hemorrhage and congestion. In addition, there was reduction in the GSH, HO-1 levels and PPARγ, eNOS gene expressions. PIO was able to reduce these induced OIR changes to levels insignificant from control group. This protective effect of PIO may be attributed to its PPARγ agonist effect, anti-inflammatory, anti-apoptotic and anti-oxidant properties.

Cadmium (Cd) intoxication in human occurs through inhalation of cigarette smoke and ingestion of contaminated water and food. We investigated the role of nebivolol (NEB) in Cd induced hepatotoxicity. In our study; NEB was given as (10 mg/kg/d) orally to rats for 6 weeks, in the presence or absence of hepatotoxicity induced by oral administration of Cd (7 mg/kg/d) for 6 weeks. Levels of serum liver enzyme biomarkers; alanine transaminase (ALT), aspartate transaminase (AST) and serum total antioxidant capacity (TAC) were measured. In addition; mean arterial pressure and total cholesterol levels were measured. Hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) were detected. Hepatic histopathological features, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) immunoexpressions were evaluated. Tumor necrosis factor alpha (TNF-α) and B-cell lymphoma-2 (Bcl-2) mRNA gene expressions were detected using real time-PCR (rt-PCR). Our results showed marked increase in all measured parameters except SOD, TAC, eNOS immunoexpression and Bcl2 mRNA gene expression which decreased in Cd induced hepatotoxicity group. NEB showed marvelous protective effect against Cd induced changes. NEB decreased liver enzymes (ALT and AST), mean arterial pressure, total cholesterol levels, MDA, iNOS immunoexpression and TNF-α gene expression but significantly increased SOD, TAC, eNOS immunoexpression and Bcl-2 gene expression. Moreover; NEB markedly improved the histopathological changes induced by Cd. These findings prove the antioxidant, anti-apoptotic and anti-inflammatory properties of NEB and its protective role in Cd induced hepatotoxicity.

Cadmium (Cd) is a highly toxic heavy metal with several harmful effects including cardiotoxicity. For the first time, we aimed to evaluate the possible cardioprotective effect of carvedilol (CAR) in Cd induced cardiotoxicity and study the mechanisms involved in such protection including endothelial nitric oxide synthase (eNOS) and HO1/Nrf2 pathway. CAR (1,10 mg/kg/d) was administered orally for 4 weeks with Cd induced cardiac injury (3 mg/kg/d) orally for 4 weeks. We measured cardiac enzymes, mean arterial pressure changes, heme oxygenase-1 (HO1) and total antioxidant capacity (TAC). Moreover; cardiac tissue malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), western blotting of caspase3 and eNOS levels and histopathology were evaluated. Immunoexpression of eNOS in cardiac tissue, gene expression changes of HO1, and nuclear factor erythroid 2-related factor 2 (Nrf2) using real time polymerase chain reactions (rtPCR) were detected. Our results showed that CAR could significantly decrease Cd induced cardiotoxicity.

Endometrial hyperplasia (EH) is a common gynecological condition and may progress to carcinoma. We investigated the effect of diacerein (DIA) on estradiol benzoate (EB)-induced EH and atypia. DIA (50 mg/kg/day) was administered orally to rats for 4 weeks, in the presence or absence of EH induced by intramuscular injection of EB (60 μg/100 g) three times per week for 4 weeks. We measured levels of serum total cholesterol, uterine tissue malondialdehyde (MDA), total nitrites (NOx ), superoxide dismutase (SOD) activity, caspase-3, interleukin-1b (IL-1b) immunoexpressions, and histopathology. Results showed that EB-induced EH and atypia manifested by significant increase in serum total cholesterol with increase in MDA and NOx levels. EB showed the typical histopathological changes of EH and atypia. In addition, there was reduction in SOD activity and decrease in caspase-3 immunoexpressions but increase in IL-1b immunoexpressions. DIA was able to reduce EB-induced pathological changes.