mTORC2:The“Ace in the Hole”for a Broader Control of Epileptic Seizures?

Over 70 million people worldwide suffer from epilepsy-one of the most prevalent chronic neurological disorders[1].Despite the availability of over thirty anti-seizure drugs(ASDs)that mainly act on voltage-gated ion channels or inhibitory GABAergic receptors,the effectiveness of these drugs in achieving seizure freedom remains unsatisfactory due to pharmacoresistance and the inevitable occurrence of side-effects.

Inhibition of hypoxia and serum deprivation-induced apoptosis by salvianolic acid in rat mesenchymal stem cells

OBJECTIVE:To investigate the influence and mechanism of salvianolic acid B(SalB) on apoptosis inhibition in rat bone marrow-derived mesenchymal stem cells(BMSCs) induced by hypoxia and serum deprivation(hypoxia/SD).METHODS:SalB concentration of 0.1,1,10 or 100 mg/L(drug groups) were investigated for their ability to inhibit apoptosis in rat BMSCs.BMSCs in both the apoptosis model and drug groups were cultured under hypoxic conditions for 6 h,after which cell apoptosis and change in mitochondrial membrane potential(MMP) were detected using flow cytometry.Activation of caspase-3 was detected using western blot analysis.RESULTS:Hypoxia/SD induced apoptosis in rat BMSCs.The early apoptosis rate was lower in the drug groups compared to the apoptosis model group(P<0.05).SalB was found to inhibit the reduction in MMP and decrease the activation of caspase-3.CONCLUSION:0.1,1 and 10 mg/L of SalB inhibits activation of caspase-3 and early apoptosis of rat BMSCs induced by hypoxia/SD and could therefore enhance the survival rate of grafted stem cells.

Effects of Agkistrodon in Different Dosage Forms on Collagen-Induced Arthritis in Rats

Objectives： To determine the effective dosage and formulation of agkistrodon in collagen-induced arthritis（CIA） rats. Methods： CIA was induced by injection of collagen in complete/incomplete Freund＇s adjuvant. Agkistrodon decoction, agkistrodon powder, and agkistrodon wine were administered daily starting from the onset of arthritis. Paw swelling degree was measured by using a volume-measuring instrument every 7 days after primary immunization. Arthritis index was measured and calculated using the ＂five scoring method＂ every 7 days. The levels of serum interleukin-1β（IL-1β） and type Ⅱ collagen Ig G antibodies were detected by enzyme-linked immunosorbent assay. Finally, all ankles were removed, and X-ray radiography was performed with In-vivo Imaging System FX. Samples were counterstained with hematoxylin and eosin for analysis. Results： Among the various dosage formulations of agkistrodon, high-dose powder, which was equivalent to an amount of 6 g/day in adults, showed better effects on the inhibition of joint swelling and reduction of arthritis index score. The relatively low levels of serum IL-1 and anti-type Ⅱ collagen Ig G antibodies, as well as the X-ray radiography and pathology results, further proved the superiority of the high-dose powder over the other formulations. The effect of decoction on inhibiting joint swelling was inversely proportional to the dosage. Other effects, such as reduction of arthritis index score and the levels of serum IL-1 and anti-type Ⅱ collagen Ig G antibodies, were directly proportional to the dosage. While the use of large dose agkistrodon wine led to negative effects. Conclusions： These data highlight the potential function of high-dose agkistrodon powder, which was equivalent to an amount of 6 g/day in adults. The powder can quickly relieve the symptoms of rheumatoid arthritis and prevent aggravation of disease, especially during the early period.