Aim: The objective of the present study was to detect Neospora caninum DNA in the placenta of sheep and evaluate the association of risk factors to polymerase chain reaction (PCR) positive and histopathological analysis of the placenta and fetal tissue samples of aborted fetuses. Materials and Methods: Fresh placenta from 51 aborted ewes was collected for PCR assay. Placental and fetal tissues of aborted fetuses, including brain, heart, liver, lung, and thymus, were collected for histopathological analysis, besides the risk factor data were obtained during the time of sampling. Results: From 51 placentas examined by PCR, 13.73% appeared positive to N. caninum DNA. The relationship between PCR positive and the risk factors revealed a significant difference (p<0.05) in age of the dam, fetal age, feed source, water source, and the presence of other animals at farm, whereas the type of birth, stillbirth, and size of flock showed insignificant difference (p>0.05). Histopathological investigation of placental and fetal tissues of positive samples showed tissue cyst-like structure, necrotic foci, and infiltration of mononuclear cells. Other lesions were thickening in chorionic plate in placenta, severe vacuolization and death of neurons, microgliosis, demyelination, edema, and proliferation of astrocytes in brain. In addition, fibrous and fat deposition with stenosis in the heart, parenchymal necrosis, severe atrophy, vacuolization and hyalinization of hepatocytes, megakaryocyte, portal fibrosis in the liver, and interlobular septal thickening in lung without obvious lesions is seen in the thymus tissue samples. Conclusion: This is a unique study that confirmed N. caninum DNA in the placenta of aborted ewes in Iraq using PCR assay. Histopathological analysis of some aborted fetuses organs could provide a more confirmatory and reliable data for a significant role of neosporosis in increasing the rate of abortion in sheep, while the clinical data of risk factors could be used to control the transmission of N. caninum infection.

Accumulation of tissue factor (TF) within cells leads to cellular apoptosis mediated through p38 and p53 pathways. In this study, the involvement of Src1 in the induction of TF-mediated cell apoptosis, and the mechanisms of Src1 activation were investigated. Human coronary artery endothelial cell (HCAEC) were transfected with plasmids to express the wild-type TF (TF Wt-tGFP), or a mutant (Ser253 → Ala) which is incapable of being released from cells (TF Ala253-tGFP). The cells were then activated with PAR2-agonist peptide (SLIGKV-NH) and the phosphorylation of Src and Rac, and also the kinase activity of Src were assessed. Transfected cells were also pre-incubated with pp60c Src inhibitor, FAK inhibitor-14, or a blocking anti-β1-integrin antibody prior to activation and the phosphorylation of p38 as well as cellular apoptosis was examined. Finally, cells were co-transfected with the plasmids, together with a Src1-specific siRNA, activated as above and the cellular apoptosis measured. Activation of PAR2 lead to the phosphorylation of Src1 and Rac1 proteins at 60 min regardless of TF expression. Moreover, Src phosphorylation and kinase activity was prolonged up to 100 min in the presence of TF, with a significantly higher magnitude when the non-releasable TF Ala253-tGFP was expressed in HCAEC. Inhibition of Src with pp60c, or suppression of Src1 expression in cells, reduced p38 phosphorylation and prevented cellular apoptosis. In contrast, inhibition of FAK had no significant influence on Src kinase activity or cellular apoptosis. Finally, pre-incubation of cells with an inhibitory anti-β1-integrin antibody reduced both Src1 activation and cellular apoptosis. Our data show for the first time that the over-activation of Src1 is a mediator of TF-induced cellular apoptosis in endothelial cells through a mechanism that is dependent on its interaction with β1-integrin.

Background and Aim: Hyperglycemia associated with hyper- or hypo-insulinemia is a hallmark of type 2 diabetes mellitus, which is firmly linked to decreased male infertility. Recently, bee venom (BV) has shown potential health prosperities, including antidiabetic; however, no study focuses on the effect of BV on male fertility in diabetic conditions. This study aimed to detect the effect of BV on histological and hormonal alteration of the testis in diabetic mice. Materials and Methods: Twenty adult male mice were selected and assigned to four groups: Control, diabetic (150 mg/kg alloxan), BV1 (diabetic + 0.5 mg/kg BV), and BV2 (diabetic + 1 mg/kg BV). After 35 days, the serum levels of glucose, insulin, testosterone, follicular-stimulating hormone, luteinizing hormone, and prolactin were estimated. The histological structure of the testes was also evaluated. Results: Alloxan-induced hyperglycemia and decreased insulin concentrations were reversed significantly by BV. Furthermore, diabetic mice exhibited various alterations in fertility hormones, while these disturbances were improved considerably to normal concentrations by BV. Similarly, alloxan-induced changes in sperm and testis histological parameters such as motility, viability, abnormality, sperm count, the number and diameter of seminiferous tubules, and the number of Leydig and Sertoli cells were significantly ameliorated to the normal condition by BV. Changes in the number, size, and shape of seminiferous tubules, the number of Leydig and Sertoli cells, and initial degeneration and vacuolization in interstitial cells and spermatogonia and spermatocyte were seen in diabetic mice. All these changes were shifted almost to normal structure by BV. Conclusion: The BV could be used as an alternative therapeutic agent that manages the markers related to diabetic conditions concomitant with the improved histological structure of the testes and hormone production to accelerate male fertility.

Breast cancer (BC) is the primary cause of women cancer death, which could be prevented by EGCG that has been recently shown several health properties included anti-cancer, however the mechanism underpinning still poorly understood. In this study, several biological activities of both MCF7 and MDA-MB-231 cells were evaluated in response to EGCG. Cell viability and the role of Akt and AMPK inhibitor molecules, and sodium pyruvate on this viability, apoptosis, metastasis, and interestingly regulation of glucose metabolism were assessed. EGCG promoted cytotoxicity in both BC cell lines after 24h but not less. Co-incubated cells with Akt and AMPK inhibitors alongside EGCG significantly caused more reduction in cell viability compared to the effect of EGCG alone with maximum effect referred to Akt inhibitor. While supplemented sodium pyruvate significantly restored the decreases in cell viability. Remarkably, EGCG induced apoptosis through increased caspase 3/7 activation associated with upregulated Bax gene, in addition to anti-metastatic effect through decreasing cellular migration. Importantly, lactate production was sharply reduced after 6h (no alteration of viable cells) and 24h (decreased viable cells) concomitant with significant blocked glucose uptake in response to EGCG. In conclusion, EGCG could be a potential anti-migration, the anti-cancerous therapeutic agent through targeting cancer cells glucose metabolism.