Our results suggest that inhibitors of ROS production or MAPK activation are involved in reduction of cardiac PPARdelta expression in response to hyperglycaemia.

Epilepsy is a neurological disorder characterized by spontaneous, recurrent and paroxysmal cerebral discharge, clinically leading to persistent alterations in function and morphology of neurons. Oxidative stress is one of possible mechanisms in the pathogenesis of epilepsy. Oxidative stress resulting from mitochondrial dysfunction gradually disrupts the intracellular calcium homeostasis, which modulates neuronal excitability and synaptic transmission making neurons more vulnerable to additional stress, and leads to neuronal loss in epilepsy. In addition, the high oxidative status is associated with the severity and recurrence of epileptic seizure. Hence, treatment with antioxidants is critically important in epileptic patients through scavenging the excessive free radicals to protect the neuronal loss. In this review, we reviewed the recent findings that focus on the role for antioxidants in prevention of mitochondrial dysfunction and the correlation between oxidative status and disease prognosis in patients with epilepsy.

The present study was designed to investigate the antihyperglycemic activity of chitosan of Podophthalmus vigil on normal and streptozotocin (STZ) diabetic rats. Diabetes was induced into male albino wistar rats by intraperitonial administration of STZ. Chitosan was administered orally at three different doses to normal and STZ-diabetic rats for 30 days. The diabetic rats showed an increase in levels of blood glucose and glycosylated hemoglobin (HbA1c) and a decrease in the levels of insulin and hemoglobin addition, diabetic rats showed a significant reduction in the activity of glucokinase and an elevation in the activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1, 6-bisphosphatase. Treatment with chitosan significantly decreased plasma glucose and HbA1c, and increased the insulin and Hb. Chitosan administration to diabetic rats reversed these enzyme activities in a significant manner. Thus, the results show that chitosan possesses an antihyperglycemic activity in the control of diabetes. The 300 mg dose of the extract produced a better effect than 100 and 200 mg doses.

In the present study, we investigated the mechanism(s) for glucose-lowering action of andrographolide in streptozotocin-induced diabetic rats (STZ-diabetic rats). Andrographolide lowered plasma glucose concentrations in a dose-dependent manner and increased plasma beta-endorphin-like immunoreactivity (BER) dose-dependently in diabetic rats. Both of these responses to andrographolide were abolished by the pretreatment of animals with prazosin or N-(2-(2-cyclopropylmethoxy) ethyl) 5-choro-alpha-dimethyl-1H-indole-3-thylamine (RS17053) at doses sufficient to block alpha1-adrenoceptors (ARs). Also, andrographolide enhanced BER release from isolated rat adrenal medulla in a concentration-related manner that could be abolished by alpha1-ARs antagonists. Bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of andrographolide, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Andrographolide failed to lower plasma glucose in the presence of opioid micro-receptor antagonists and in the opioid micro-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with andrographolide resulted in the reduced expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver and an increased expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle. These effects were also blocked by opioid micro-receptor antagonists. In conclusion, our results suggest that andrographolide may activate alpha1-ARs to enhance the secretion of beta-endorphin which can stimulate the opioid micro-receptors to reduce hepatic gluconeogenesis and to enhance the glucose uptake in soleus muscle, resulting in a decrease of plasma glucose in STZ-diabetic rats. However, the roles of other endogenous opioid peptides or the mixture of several opioid peptides in the activation of opioid micro-receptors associated with the plasma glucose-lowering action of andrographolide, should be considered and need more investigation in the future.

Digoxin has been used as an inotropic agent in heart failure for a long time. Troponin I (TnI) phosphorylation is related to cardiac contractility, and the genes are regulated by peroxisome proliferator-activated receptors (PPARs). Our previous studies indicated that cardiac abnormality related to the depressed expression of PPARd in the hearts of STZ rats is reversed by digoxin. However, the cellular mechanisms for this effect of digoxin have not been elucidated. The aim of the present study was to investigate possible mechanisms for this effect of digoxin using the H9c2 cell line cultured in high glucose (HG) conditions. METHODSThe effects of digoxin on PPARd expression, intracellular calcium and TnI phosphorylation were investigated in cultured H9c2 cells, maintained in a HG medium, by using Western blot analysis. RESULTSDigoxin increased PPARd expression in H9c2 cells subjected to HG conditions, and increase the intracellular calcium concentration. This effect of digoxin was blocked by BAPTA-AM at concentrations sufficient to chelate calcium ions. In addition, the calcineurin inhibitor cyclosporine A and KN93, an inhibitor of calcium/calmodulin-dependent protein kinase, inhibited this action. Digoxin also increased TnI phosphorylation and this was inhibited when PPARd was silenced by the addition of RNAi to the cells. Similar changes were observed on the contraction of H9c2 cells. CONCLUSIONThe results suggest that digoxin appears, through calcium-triggered signals, to reverse the reduced expression of PPARd in H9c2 cells caused by HG treatment.

Non-small-cell lung cancer (NSCLC) is one of the most common lung cancers, and microRNAs (miRNAs) have been reported to play essential roles in NSCLC. Recent studies have indicated that miR-330-3p expression is up-regulated in NSCLC samples and in tissues of NSCLC brain metastasis. In this study, up-regulation of miR-330-3p expression was confirmed in NSCLC and 20 NSCLC patient samples. Furthermore, miR-330-3p was over-expressed in NSCLC cell lines A549 and H23, and the promotive function of miR-330-3p was investigated in regulating NSCLC cell proliferation and cell cycle distribution. To identify potential target genes of miR-330-3p in NSCLC, the miRNA target prediction databases were used. Luciferase activity assay and real-time RT-PCR analysis confirmed that miR-330-3p is negatively correlated with the expression of early growth response 2 (EGR2). Moreover, it was also found that EGR2 mRNA contains two potential binding sites for miR-330-3p. Knock-down of EGR2 with siRNA was demonstrated to have a similar effect as the over-expression of miR-330-3p in NSCLC cell lines. Taken together, our results show that EGR2 is a target of miR-330-3p.

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