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We aimed to study the protective effects of 3-n-butylphthalide (NBP) on cerebral infarction induced by local ischemic injury and regulation mechanism of the PI3K/Akt/GSK-3ß signaling pathway. One hundred male Wistar rats aged 12-15 weeks were randomly divided into 5 groups (n=20). The middle cerebral artery occlusion (MCAO) model was established. NBP, P13K specific inhibitor LY294002 and NBP plus LY294002 groups were intraperitoneally administered on the first day after modeling, once a day for 7 days. Sham operation (Sham) and model groups were intraperitoneally given equal amounts of normal saline. Neuronal damage was detected by Nissl staining. Intact neurons were counted under light microscope. The protein expressions of Akt, P-Akt, GSK-3ß and P-GSK-3ß were detected by Western blotting. The mNS score of NBP group decreased significantly compared with that of model group (P<0.05). Compared with model group, the cerebral infarction volume of NBP group significantly reduced (P<0.05). Compared with model group, the number of intact neurons in NBP group significantly increased (P<0.05). Compared with model group, the phosphorylation levels of Akt and GSK-3ß in NBP group significantly increased (P<0.05). By activating the PI3K/Akt/GSK-3ß signaling pathway, NBP relieves neurological function damage and protects against cerebral infarction induced by local ischemic injury. [ABSTRACT FROM AUTHOR]

Sinapic acid (SA), one of the hydroxycinnamic acid derivatives, has powerful antioxidant and anti-inflammatory characteristics. Moreover, SA has also been shown to have an apoptotic effect against various cancer cells. Here, we investigated the cytotoxic and apoptotic effects of sinapic acid on D17 canine osteosarcoma cell line. We measured the properties of SA on cell viability with the XTT test and found its IC50 dose at 750 µmol at 72 h. We analyzed the effects on gene expression of apoptosis pathways by qRT-PCR. qRT-PCR results revealed significant increases in the mRNA level expressions of BAX, CASP3, CASP7, CASP8, CASP9, FAS and P53; whereas, there was a statistically insignificant downregulation in CYCS level and increase in BCL2 level. Our findings show that SA can induce apoptosis in the D17 cell line. [ABSTRACT FROM AUTHOR]

Usage of oocytes obtained from ovaries aft er long-term cold storage for in vitro embryo production is a promising tool for the protection of wildlife and endangered animal species. Mammalian oocytes are susceptible to oxidative stress with regard to the high lipid content of plasma membranes. Melatonin is known as a powerful antioxidant and anti-apoptotic agent due to its ability to eliminate toxic oxygen derivatives and reduce the formation of reactive species. Th is study was performed to verify the optimal environmental conditions for long-term preservation of cat ovaries (Felis domesticus) by adding diff erent concentrations of melatonin (500, 750 and 1000 µM) to the storage medium (0.9% NaCl) as an antioxidant to be preserved at 4°C for 24 h. To determine the eff ect of melatonin on cat oocytes collected from stored ovaries, the anti and pro- apoptotic gene levels in cumulus oophorus, the in vitro maturation rates, the cell membrane and oocytes viability were evaluated. In all melatonin added groups regardless of whether they are stored in the cold; Pro-apoptotic gene levels (BAX) were determined to be upregulated however, anti- apoptotic gene levels (BCL-2) were downregulated in cumulus cells (P<0.05). Th e cell membrane stability and cell viability rates of oocytes began to deteriorate in parallel with the rate of melatonin increase. In parallel with these findings, in vitro maturation rates of oocytes were negatively aff ected as the amount of melatonin increased (P≤0.001). In conclusion the results showed that adding melatonin (500,750 or 1000 µM) to the ovarian transport and storage medium had negative eff ect on in vitro maturation rate, viability and cell membrane structure of cat oocytes. [ABSTRACT FROM AUTHOR]

Lead (Pb) poisoning and the induced potential of the lesion is a global concern with harmful effects on multiple body systems, particularly the liver system. In this study, we have investigated the efficacy of aqueous-alcoholic extract of parsley leaves (PAE), which is a component of flavonoids that could play an important role in the antioxidant property, in preventing liver Pb-damages. For this, sixty adult male rats were randomly divided into six groups in a factorial arrangement: control; receiving oral gavage for 21 days with 2 mL water; 500 ppm Pb; 100 and 200 mg/kg PAE in combination form with Pb, and 200 mg/kg PAE. Liver enzymes and oxidative stress indexes were computed for liver stress, in blood serum. Apoptosis levels were assessed in the evaluation of liver gene expression. Data indicated that Pb reduced liver weight and feed intake. The results showed that Pb significantly increased the liver enzymes contents in the blood serum in the comparison vehicle group. Furthermore, the MDA contents of the Pb group rats were significantly more than that of the vehicle group. Likewise, T-AOC and the activities of CAT and SOD were significantly reduced. Meanwhile, Pb administration induced liver apoptosis-related genes by upregulating Bax and TNF-α genes and downregulating the Bcl-2 gene of animals. At the same time, administration of PAE significantly improved liver oxidative and apoptosis changes. Thus, this study provides a novel mechanistic approach concerning Pb-induced toxicity, due to PAE antioxidant activity. [ABSTRACT FROM AUTHOR]

Cancer is a major health problem in dogs. Types of cancer seen in dogs include melanoma, Non-Hodgkin lymphoma, osteosarcoma, soft tissue sarcomas and prostate, breast, lung and colorectal carcinomas. Osteosarcoma (OSA) is the most common malignant primary bone tumor in domestic dogs. It constitutes 85% of skeletal tumors. It is derived from primitive bone cells that occur in both the appendicular (~75%) and axial (~25%) skeleton. The present study was intended to determine the cytotoxic and apoptotic effects of curcumin administration at certain doses and in certain periods on D-17 canine osteosarcoma cells. Canine osteosarcoma cells were treated with curcumin and the effects of it on proliferation were determined by WST-1, apoptosis by caspase 3/7 activity (MuseCaspase 3/7) and the ratio of proapoptotic Bax gene to antiapoptotic Bcl-2 gene expression level by qRT-PCR. Our data demonstrated that curcumin decreased cell proliferation and viability, ultimately inducing caspase 3/7 mediated apoptosis in treated D-17 canine osteosarcoma cells. Furthermore, the application of curcumin on canine osteosarcoma cells downregulated the expression of Bcl-2 and upregulated the expression of proapoptotic gene Bax. Thus, these results may provide a basis for further study of curcumin in the treatment of canine osteosarcoma. [ABSTRACT FROM AUTHOR]

This study aims to highlight the cellular and molecular events of atresia in the Bedouin goat ovarian follicles. Ovaries collected from slaughterhouses during breeding and non-breeding seasons were submitted to morphological studies and immunolocalization of active caspase-3. The results showed that ovaries were heavier (P<0.05) during the breeding season. The atresia occurred at all stages of follicular development in breeding and non-breeding seasons. At the preantral stage, degeneration affected primarily oocyte and active caspase-3 immunoreactivity was detected in the oocyte with a few staining in follicular cells. At the antral stage, atresia affected in first the granulosa layer cells which were characterized by an abnormal indentation of nuclei and positive active caspase-3 immunolabeling. At the early stage of atresia, the granulosa cells exhibited a few pycnotic nuclei and lost their cellular integrity, by getting scattered; these cells were positive to active caspase-3. At the late stage, the scattered cells invaded the antral cavity and the dead cells were eliminated by phagocytic cells. The oocyte seemed to undertake a long process of atresia via an autophagic pathway and it was the last to die. Finally, the follicle was replaced by a collagen fiber forming a scar of atresia. In conclusion, important morphological changes occurred in atretic follicles mainly in antral stage by apoptosis via caspase-3 signaling pathway, in breeding and non-breeding seasons. [ABSTRACT FROM AUTHOR]

Brucellosis is serious zoonotic disease affecting both animals and humans. Brucella inhibits the apoptosis of host macrophages. And the JAK2/STAT3 pathway regulates various cellular physiological activities. However, the association between Brucella-mediated inhibition of macrophage apoptosis and regulation of the JAK2/STAT3 pathway is unclear. In the current study, We tested the the activation of JAK2/ STAT3 pathway and evaluated its function during Brucella M5-90 infection in cells. The result was found that infection with Brucella M5-90 activated the JAK2/STAT3 pathway and induced phosphorylation of both JAK2 and STAT3 in a time-dependent manner. JAK2 and STAT3 phosphorylation were inhibited by AG490 in a dose-dependent manner. Inhibition of the JAK2/STAT3 pathway with AG490 significantly induced proinflammatory responses, macrophage apoptosis at the transcriptional and protein levels, as well as intracellular survival and replication of Brucella M5-90. This study indicates that the JAK2/STAT3 pathway plays a major role in macrophage apoptosis induced by infection with Brucella M5-90. In addition, TNF-α plays a major role in the regulation of the JAK2/STAT6 pathway during Brucella M5-90 infection. The above information may help to unravel the pathogenic mechanism of Brucella infection. [ABSTRACT FROM AUTHOR]

This study aimed to investigate responsible mechanisms for rapid intestinal catch-up growth in intrauterine growth restriction (IUGR) pups via analysis of autophagy, apoptosis and proliferation in a rat model. Twenty primiparous dams were assigned into two groups as 1) dams with feed ad libitum (Adlib) and 2) dams with 50% feed restriction from gestational day 10 to 21 to achieve normal birth weight (NBW) and IUGR pups, respectively. Litter size and pup weight were recorded at parturition and 8 pups were kept in each litter to have sufficient colostrum for 24 h. Subsequently, 2 pups from each litter were decapitated. Results indicated that feed restriction dams had similar litter size with rats in Adlib group although produced IUGR pups. Histological analysis indicated that IUGR rats had decreased villus height and surface area in jejunum. There was an accumulation of autophagosomes in jejunal mucosa of IUGR pups, however, the mitochondria and microvilli were unaffected. mRNA expressions of WIPI1, MAP1LC3B, Atg13, ULK1 and Beclin1 were increased, and mTOR expression was decreased in jejunum of IUGR, which also had lower Bcl-2 mRNA expression, increased caspase 9 and relative increased ki67 mRNA expression. Results suggested that after feeding colostrum, IUGR pups had impaired jejunum with unaffected mitochondrial histology. Enhanced intestinal autophagy under low-stress conditions might improve intestinal proliferation, which may be contributed to the rapid intestinal catch-up growth. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of naturally occurring, short, endogenous, noncoding RNA molecules (~22 nt) involved in a wide variety of regulatory pathways, including cell growth, development, differentiation, proliferation, and apoptosis, as well as viral defense, hematopoiesis, organ formation, and metabolism. Previous studies showed that bta-miR-193a (miR-193a) was upregulated in Madin-Darby bovine kidney (MDBK) cells infected with bovine viral diarrhea virus (BVDV) strain NADL; however, the role of miR-193a in apoptosis-associated regulation remains unclear. In this study, we found that miR-193a is a novel regulator of MDBK apoptosis and that lentiviral infection exhibited a positive effect on miR-193a expression. Additionally, we observed that the miR-193a-target sequence was present in the 3'-untranslated region of B-cell lymphoma-2-associated X protein (BAX) mRNA, with miR-193a overexpression resulting in reduced BAX mRNA and protein levels. Furthermore, we observed that miR-193a promoted apoptosis and inhibited BVDV strain NADL replication according to quantitative reverse transcription polymerase chain reaction results. These findings confirmed miR-193a as a positive regulator of apoptosis and provided a theoretical basis for the important role of miRNAs in regulating BVDV replication. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of chitosan oligosaccharides (COS) on the antioxidative function, lymphocyte cycle and apoptosis of ileum mucosa in broiler. 640 AA broilers were randomly allocated into four groups, which were fed with diets supplemented 0, 200, 350 and 500 mg/kg of COS for six weeks, respectively. The results showed that compared with the control group, the activities of glutathione peroxidase and superoxide dismutase, the ability of total antioxidant capacity and inhibit hydroxy radical as well as the contents of glutathione in the 350 and 500 mg/kg COS groups were significantly increased, while the levels of malonedialdehyde were significantly decreased. The percentages of S and gap 2/mitosis (G2M) phases and proliferating index of ileum mucosal lymphocytes in the 350 and 500 mg/kg COS groups were increased, but, the percentages of apoptotic ileac lymphocytes were not significantly different compared with the control group. No significant difference in the levels of antioxidant function mentioned above, cell cycle phase distribution and the percentages of apoptotic ileac lymphocyte existed between the 350 and 500 mg/kg COS groups. Conclusion: dietary chitosan oligosaccharides supplements with 350 mg/kg and 500 mg/kg could improve the antioxidant function and accelerate lymphocytes proliferation, but had non-influence on lymphocytes apoptosis in the ileum mucosa of broiler. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the effects of different doses of boric acid injected into chicken eggs on bursa of Fabricius and spleen. The study material consisted of three treatment and one control group. On the fourth day of incubation, boric acid dissolved in 0.9% NaCl were injected into eggs at 1.000, 1.500 and 2.000 ppm doses and control group received only 0.9% NaCl injection. Chicks hatched were raised until ten weeks of age (n=10). Bursa of Fabricius and spleen were evaluated by histological, immunohistochemical and stereological methods. Weight of bursa of Fabricius, relative weight of bursa of Fabricius (P<0.01), volume of bursa of Fabricius, cortical thickness, follicle area and area of follicular medulla significantly reduced (P<0.001) by injection of 1.500 ppm boric acid compared to control group. The number of white blood cells also decreased in 1.000 ppm and 1.500 ppm groups. An increase (P<0.001) was recorded in hemoglobin ratio in 2.000 ppm group when compared with the other treatment groups and control group. There was an increase in 1500 ppm group in terms of spleen weight (P<0.001), relative spleen weight (P<0.01) and plasma cell count (P<0.05) and likewise an increase was noted in 1.000 and 2.000 ppm groups with respect to follicle count and number of apoptotic cells in comparison to control group. In conclusion, low doses of boric acid induced the bursal involution and implicitly increased plasma cell count in the spleen. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the protective effects of kefir in the liver damage of rats, at experimental carbon tetrachloride (CCU) intoxication by histologically and immunohistochemically. During the 45 days trial period, 18, female, Wistar albino rats were used. One of them was control, three experimental group was created. Twice a week 0.5 cc carbon tetrachloride (CCI4) + olive-oil (1:1) suspension was injected subcutaneously to the second and third group. At third group additionally to this administration 30 ml kefir was given daily by oral gavage. CCI4-induced hepatocellular damage and apoptosis was observed but these adverse findings reduced with kefir administration.These findings indicate that kefir may have a protective role at liver damage. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the effects of high level of nitric oxide (NO) production and oxidative stress (OS) on nephropathology and to identify whether NO and OS have any correlation with apoptosis seen in diabetic kidney, elucidating the underlying mechanism(s) involved in the development of nephropathology in streptozotocin (STZ)-induced diabetic rats. Expression levels of caspase 3, caspase 9, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (İNOS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), for the detection of oxidative damage to DNA, were examined in diabetic kidney tissues. Results of the study revealed that the levels of 8-OHdG (P<0.005), eNOS (P<0.005), İNOS (P<0 005) caspase 3 (P<0.005) and caspase 9 (P<0.005) were remarkably higher in diabetic kidney tissues than in controls In addition STZ-treated animals showed significant loss of body weight and renal enlargement. It was suggested that apoptosis, OS and increased NO levels are involved in the pathogenesis of diabetic nephropathy. The results also strongly suggested that STZ-induced apoptosis through activation of the intrinsic pathway and that might be most likely related to increased NO levels. Moreover, high NO production was not only mediated by eNOS but also by İNOS Increased NO production may contribute to hyperfiltration and microalbuminuria in early diabetic nephropathy. Furthermore, expression of 8-OHdG might give an idea of the progress and may be essential as it has a diagnostic significance for this disease In conclusion we believe that eNOS and İNOS overexpressions induce diabetic nephropathy by mediating apoptosis in STZ-induced rats. [ABSTRACT FROM AUTHOR]

Mammary tumours are the most common neoplasms in intact female dogs. Dysregulation of programmed cell death mechanisms plays an important role in the pathogenesis and progression of mammary gland tumours. The aim of this study was to investigate the relationship between some anti-apoptotic proteins (Bcl-2, Bcl-XL and Bax), apoptotic index (Al) and histopathological diagnosis, tumour grading, tumour staging and survival time of canine mammary tumours (CMT). Twenty seven tissue samples were collected from twenty seven animals with mammary tumours. The samples were evaluated and graded histopathologically. All cases were staged according to the TNM system. The expression o f Bcl-2, Bcl-XL and Bax proteins was investigated using indirect immunoperoxidase test and apoptosis was evaluated usinq terminal deoxynucleotidyltransferase (TdT)-mediated nick end-labelling (TUNEL) technique. Follow-up examination and survival estimation analysis were performed. While there was a significant statistical relation between Bcl-2 expression and histopathological diagnosis (P<0.005), there was no considerable association between histopathological diagnosis and Bax, Bcl-XL and Al (P>0.05).The differences between T1 and T5, T2 andT5 stages were statistically significant in terms o f Bax expression (P<0.05), and Bax expressions were higher in T5 when compared with T1 or T2 No association between survival time and Bcl-2, Bax, Bcl-XL and Al was determined (P>0.05). Bcl-2 was overexpressed in highly malignant tumours such as solid and tubulopapillary adenocarcinomas and Bax had high expression levels in metastatic tumours. As a result, it is concluded that Bcl-2 and Bax expression can be accessory parameters for anticipating the biologic behaviour and prognosis of CMT but these markers alone are not sufficient for the determination of survival time. [ABSTRACT FROM AUTHOR]