Bax-dependent apoptosis induced by ceramide in HL-60 cells

AbstractCeramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. In this study, we show that antisense bax inhibits cytochrome c release, poly(ADP-ribose)polymerase cleavage and cell death induced by ceramide in HL-60 cells. In addition, ceramide induces translocation of Bax to mitochondria. The addition of the broad spectrum caspase inhibitor zVAD-fmk prevented ceramide-induced apoptotic cell death but did not inhibit translocation of Bax and mitochondrial cytochrome c release. Furthermore, ceramide inhibits the expression of the antiapoptotic protein Bcl-xL with an increase in the ratio of Bax to Bcl-xL. These data provide direct evidence that Bax plays an important role in regulating ceramide-induced apoptosis

A Protein Profile of Visceral Adipose Tissues Linked to Early Pathogenesis of Type 2 Diabetes Mellitus

Adipose tissue is increasingly recognized as an endocrine organ playing important pathophysiological roles in metabolic abnormalities, such as obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). In particular, visceral adipose tissue (VAT), as opposed to subcutaneous adipose tissue, is closely linked to the pathogenesis of insulin resistance and T2DM. Despite the importance of VAT, its molecular signatures related to the pathogenesis of T2DM have not been systematically explored. Here, we present comprehensive proteomic analysis of VATs in drug-naïve early T2DM patients and subjects with normal glucose tolerance. A total of 4,707 proteins were identified in LC-MS/MS experiments. Among them, 444 increased in abundance in T2DM and 328 decreased. They are involved in T2DM-related processes including inflammatory responses, peroxisome proliferator-activated receptor signaling, oxidative phosphorylation, fatty acid oxidation, and glucose metabolism. Of these proteins, we selected 11 VAT proteins that can represent alteration in early T2DM patients. Among them, up-regulation of FABP4, C1QA, S100A8, and SORBS1 and down-regulation of ACADL and PLIN4 were confirmed in VAT samples of independent early T2DM patients using Western blot. In summary, our profiling provided a comprehensive basis for understanding the link of a protein profile of VAT to early pathogenesis of T2DM. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.1

Safety and optimal neuroprotection of neu2000 in acute ischemic stroke with reCanalization: study protocol for a randomized, double-blinded, placebo-controlled, phase-II trial

BACKGROUND: The potential of neuroprotective agents should be revisited in the era of endovascular thrombectomy (EVT) for acute large-artery occlusion because their preclinical effects have been optimized for ischemia and reperfusion injury. Neu2000, a derivative of sulfasalazine, is a multi-target neuroprotectant. It selectively blocks N-methyl-D-aspartate receptors and scavenges for free radicals. This trial aimed to determine whether neuroprotectant administration before EVT is safe and leads to a more favorable outcome. METHODS: This trial is a phase-II, multicenter, three-arm, randomized, double-blinded, placebo-controlled, blinded-endpoint drug trial that enrolled participants aged ≥ 19 years undergoing an EVT attempt less than 8 h from symptom onset, with baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 8, Alberta Stroke Program Early CT score ≥ 6, evidence of large-artery occlusion, and at least moderate collaterals on computed tomography angiography. EVT-attempted patients are randomized into control, low-dose (2.75 g), and high-dose (5.25 g) Neu2000KWL over 5 days. Seventy participants per group are enrolled for 90% power, assuming that the treatment group has a 28.4% higher proportion of participants with functional independence than the placebo group. The primary outcome, based on intention-to-treat criteria is the improvement of modified Rankin Scale (mRS) scores at 3 months using a dichotomized model. Safety outcomes include symptomatic intracranial hemorrhage within 5 days. Secondary outcomes are distributional change of mRS, mean differences in NIHSS score, proportion of NIHSS score 0-2, and Barthel Index > 90 at 1 and 4 weeks, and 3 months. DISCUSSION: The trial results may provide information on new therapeutic options as multi-target neuroprotection might mitigate reperfusion injury in patients with acute ischemic stroke before EVT

MRI Findings of Pericardial Fat Necrosis: Case Report

Pericardial fat necrosis is an infrequent cause of acute chest pain and this can mimic acute myocardial infarction and acute pericarditis. We describe here a patient with the magnetic resonance imaging (MRI) findings of pericardial fat necrosis and this was correlated with the computed tomography (CT) findings. The MRI findings may be helpful for distinguishing pericardial fat necrosis from other causes of acute chest pain and from the fat-containing tumors in the cardiophrenic space of the anterior mediastinum

Reversible magnetization of MgB2 single crystals with a two-gap nature

We present reversible magnetization measurements on MgB2 single crystals in magnetic fields up to 2.5 T applied parallel to the crystal's c-axis. This magnetization is analyzed in terms of the Hao-Clem model, and various superconducting parameters, such as the critical fields [Hc(0) and Hc2(0)], the characteristic lengths [xi(0) and lambda(0)], and the Ginzburg-Landau parameter, kappa, are derived. The temperature dependence of the magnetic penetration depth, lambda(T), obtained from the Hao-Clem analysis could not be explained by theories assuming a single gap. Our data are well described by using a two-gap model.Comment: 20 pages, 1 table, 4 figures, will be published in Phys. Rev.

Measurement of 129 I Radioactivity in Groundwater of Radioactive Waste Disposal Site

The investigation of the environmental radioactivity around the radioactive waste disposal site in Gyeongju is being carried out. The radioactivity of 129 I in groundwater and seaweed are to be measured. The analytical method to measure the radioactivity of 129 I in aqueous media was established. This method contains oxidation-reduction reaction, anion-exchange separation and palladium precipitation. The 129 I radioactivity in the PdI 2 precipitates was measured by using low-energy gamma spectrometer. The counts of peak at 39.6 keV of gamma energy were used for determination of 129 I radioactivity. The chemical recovery was determined by the weights of PdI 2 precipitates. The deionized water and groundwater spiked with 129 I tracer were tested. In the case of deionized water, the relative deviations of measured concentration from spiked one are from 1.1 to 10.7%. The relative deviations of measured radioactivity from spiked one in the groundwater experiments are 2.9 and 3.7%. The measured concentration is in good agreement with spiked one. The groundwater sampled from radioactive waste disposal site was tested. The concentrations of 129 I in the groundwater are below minimum detectable activities of 36.7 and 36.6 mBq/L