The aim of the present study is to investigate the role of hyperglycemia and hyperinsulinemia in autophagy induction in the liver of male mice. Autophagy is a catabolic cellular process that recycles the aged or damaged cellular organelles and inclusions under certain circumstances. Hyperglycemia is induced by a single dose of alloxan IP injection (180 mg/kg) and hyperinsulinemia is induced by high fat diet together with glucose feeding for short period (2 weeks) and long period (3 months). Hyperglycemia and hyperinsulinemia were estimated by measuring blood glucose level by glucometer and insulin level by specific ELISA kit, respectively. Autophagy induction was investigated morphologically by electron microscopy examination and biochemically by immunodetection of microtubular associated light chain protein 3 (LC3) conversion from LC3I to LC3II form and by immunodetection of the phosphorylated and nonphosphorylated forms of mammalian target of Rapamycin (mTOR). Our results revealed that hyperglycemia and hyperinsulinemia independently induced hepatocellular autophagy as indicated by the accumulation of autophagosomes and autolysosomes in EM examination and by the increase of the level of LC3II and decrease of the phosphorylated form of mTOR in western blot analysis. This study throw the light on the autophagy of hepatocytes as a cellular mechanism induced under diabetic conditions which may contribute in better understanding of our knowledge concerning nutrients metabolic disorders.

20-Benzoyloxycinnamaldehyde (BCA) is a promising antitumor agent. BCA effectively inhibited proliferation of MDA-MB-435 more than in MCF-7 breast cancer cells. Our recent findings showed that DJ-1 protects MCF7 cells from BCA-induced oxidative stress via its mitochondrial translocation and inhibition of the mitochondrial perturbation (Ismail et al., 2012). In this study, we addressed the question of whether Nrf2 works downstream to DJ-1 in mediating differential antiproliferation effects in MCF-7 and MDAMB-435 breast cancer cells induced by BCA treatment. BCA upregulated the expression and induced nuclear translocalization of DJ-1 and Nrf2 in only MCF-7 cells. However, in MDA-MB-435, BCA increased only Nrf2 expression without inducing DJ-1 and/or Nrf2 protein translocalization to the nucleus. Furthermore, DJ-1 knockdown decreased DJ-1 expression in both cells without affecting Nrf2 and its downstream target g-GCS, suggesting that DJ-1-induced cell protection and works independent of Nrf2 signaling pathway.

20-Benzoyloxycinnamaldehyde (BCA) is a promising antitumor agent. BCA effectively inhibited proliferation of MDA-MB-435 more than in MCF-7 breast cancer cells. Our recent findings showed that DJ-1 protects MCF7 cells from BCA-induced oxidative stress via its mitochondrial translocation and inhibition of the mitochondrial perturbation (Ismail et al., 2012). In this study, we addressed the question of whether Nrf2 works downstream to DJ-1 in mediating differential antiproliferation effects in MCF-7 and MDAMB-435 breast cancer cells induced by BCA treatment. BCA upregulated the expression and induced nuclear translocalization of DJ-1 and Nrf2 in only MCF-7 cells. However, in MDA-MB-435, BCA increased only Nrf2 expression without inducing DJ-1 and/or Nrf2 protein translocalization to the nucleus. Furthermore, DJ-1 knockdown decreased DJ-1 expression in both cells without affecting Nrf2 and its downstream target g-GCS, suggesting that DJ-1-induced cell protection and works independent of Nrf2 signaling pathway.

Chloroquine is a drug derived from cinchona bark has been used for long time to treat different diseases including malaria and accidently it was proved to lower hyperglycemia. Diabetes mellitus is accompanied with many disorders including blood serum proteins levels. Taking into consideration that insulin administration controls hyperglycemia of diabetic patients but it is not sufficient to restore the level of blood serum proteins. In the present work we compared the action of chloroquine and insulin on major blood serum proteins of alloxan induced diabetes. Mice were injected once with alloxan and then treated either with chloroquine or insulin. Another category of mice were fed with high glucose diet for short or long period to induce hyperglycemia independent of insulin level. Major blood serum proteins namely; transferrin, albumin, antitrypsin, acid glycoprotein and immunoglobulin G were estimated by SDS-PAGE and Image J software. Our results showed that chloroquine and insulin were independently effective in lowering fasting blood glucose level in alloxan treated animals. Also chloroquine significantly raises blood serum insulin level in diabetic animals without exogenous insulin treatment. Chloroquine restored partially or completely the level of transferrin, antitrypsin, acid glycoprotein and immunoglobulin G significantly and more efficiently than insulin. Both chloroquine and insulin had no influence on restoring the level of albumin in diabetic mice. The results indicate that chloroquine treatment may be a good adjuvant therapy with insulin to control diabetes and its complications.

Chloroquine is a drug derived from cinchona bark has been used for long time to treat different diseases including malaria and accidently it was proved to lower hyperglycemia. Diabetes mellitus is accompanied with many disorders including blood serum proteins levels. Taking into consideration that insulin administration controls hyperglycemia of diabetic patients but it is not sufficient to restore the level of blood serum proteins. In the present work we compared the action of chloroquine and insulin on major blood serum proteins of alloxan induced diabetes. Mice were injected once with alloxan and then treated either with chloroquine or insulin. Another category of mice were fed with high glucose diet for short or long period to induce hyperglycemia independent of insulin level. Major blood serum proteins namely; transferrin, albumin, antitrypsin, acid glycoprotein and immunoglobulin G were estimated by SDS-PAGE and Image J software. Our results showed that chloroquine and insulin were independently effective in lowering fasting blood glucose level in alloxan treated animals. Also chloroquine significantly raises blood serum insulin level in diabetic animals without exogenous insulin treatment. Chloroquine restored partially or completely the level of transferrin, antitrypsin, acid glycoprotein and immunoglobulin G significantly and more efficiently than insulin. Both chloroquine and insulin had no influence on restoring the level of albumin in diabetic mice. The results indicate that chloroquine treatment may be a good adjuvant therapy with insulin to control diabetes and its complications.

In the present study, the effect of modulation of autophagy induced by anthocyanin on cell death of Human T lymphoma cells (Jurkat) was studied. Anthocyanin was abstracted from dry petals of Hibiscus sabdariffa, aquous solution of anthocyanin was added to cells at different concentrations then cell viability was determined by trypan blue exclusion method. Autophagy induced by anthocyanin was inhibited by 5 mM NH4CL which halts lysosomal enzymes and accordingly preventing autolysosomes formation. On the other hand, Autophagy was enhanced by glucose starvation. In both experiments of autophagy inhibition and enhancement, cell viability was studied to investigate the effect of autophagy modulation on cell viability. The results of this work revealed that both inhibition and enhancement of autophagy induced by anthocyanin lead to massive cell death. Immuno-detection of active caspase 3, one of the major hallmark of apoptotic cell death revealed remarkable increase of active caspse3 upon autophagy inhibition or enhancement. In conclusion, modulation of autophagy induced by anthocyanin lead to increasing of apoptotic cell death.

In the present study, the effect of modulation of autophagy induced by anthocyanin on cell death of Human T lymphoma cells (Jurkat) was studied. Anthocyanin was abstracted from dry petals of Hibiscus sabdariffa, aquous solution of anthocyanin was added to cells at different concentrations then cell viability was determined by trypan blue exclusion method. Autophagy induced by anthocyanin was inhibited by 5 mM NH4CL which halts lysosomal enzymes and accordingly preventing autolysosomes formation. On the other hand, Autophagy was enhanced by glucose starvation. In both experiments of autophagy inhibition and enhancement, cell viability was studied to investigate the effect of autophagy modulation on cell viability. The results of this work revealed that both inhibition and enhancement of autophagy induced by anthocyanin lead to massive cell death. Immuno-detection of active caspase 3, one of the major hallmark of apoptotic cell death revealed remarkable increase of active caspse3 upon autophagy inhibition or enhancement. In conclusion, modulation of autophagy induced by anthocyanin lead to increasing of apoptotic cell death.

Groundwater is the only water resource across the "hyper" arid Eastern Sahara. Management of this resource is imperative for the sustainable development approaches. A 3D GIS-based groundwater flow model for the Nubian Sandstone Aquifer System (NSAS) was developed to simulate the groundwater management options for the different development areas/oases within the aquifer, and to predict the environmental impact of the present and future groundwater extraction schemes on the whole system. Based on the actual and planned extraction rates of the NSAS, five extraction scenarios were suggested to investigate the most feasible groundwater management option in terms of the economic lifting depth until year 2100. The model was calibrated and validated under the transient conditions. The calibrated model was then used for the prediction simulations and the local modeling. The results of simulating the present extraction rates of the NSAS until 2100 showed that the free flowing phenomenon will disappear all over the modeled area. At this simulation time, a groundwater volume of 354 km³ will be extracted from the aquifer storage. Scenario 3 was found to be the optimal groundwater management option that meets the development ambitions and in the same time keeps the safe economic lifting depth as well.

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