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

Agmatine modulates the phenotype of macrophage acute phase after spinal cord injury in rats

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/ kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206+ & ED1+ cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype. © Experimental Neurobiology 201

PwRn1, a novel Ty3/gypsy-like retrotransposon of Paragonimus westermani: molecular characters and its differentially preserved mobile potential according to host chromosomal polyploidy

<p>Abstract</p> <p>Background</p> <p>Retrotransposons have been known to involve in the remodeling and evolution of host genome. These reverse transcribing elements, which show a complex evolutionary pathway with diverse intermediate forms, have been comprehensively analyzed from a wide range of host genomes, while the information remains limited to only a few species in the phylum Platyhelminthes.</p> <p>Results</p> <p>A LTR retrotransposon and its homologs with a strong phylogenetic affinity toward <it>CsRn1 </it>of <it>Clonorchis sinensis </it>were isolated from a trematode parasite <it>Paragonimus westermani </it>via a degenerate PCR method and from an insect species <it>Anopheles gambiae </it>by <it>in silico </it>analysis of the whole mosquito genome, respectively. These elements, designated <it>PwRn1 </it>and <it>AgCR-1 </it>– <it>AgCR-14 </it>conserved unique features including a t-RNA^Trpprimer binding site and the unusual CHCC signature of Gag proteins. Their flanking LTRs displayed >97% nucleotide identities and thus, these elements were likely to have expanded recently in the trematode and insect genomes. They evolved heterogeneous expression strategies: a single fused ORF, two separate ORFs with an identical reading frame and two ORFs overlapped by -1 frameshifting. Phylogenetic analyses suggested that the elements with the separate ORFs had evolved from an ancestral form(s) with the overlapped ORFs. The mobile potential of <it>PwRn1 </it>was likely to be maintained differentially in association with the karyotype of host genomes, as was examined by the presence/absence of intergenomic polymorphism and mRNA transcripts.</p> <p>Conclusion</p> <p>Our results on the structural diversity of <it>CsRn1</it>-like elements can provide a molecular tool to dissect a more detailed evolutionary episode of LTR retrotransposons. The <it>PwRn1</it>-associated genomic polymorphism, which is substantial in diploids, will also be informative in addressing genomic diversification following inter-/intra-specific hybridization in <it>P. westermani </it>populations.</p

Tip-Enhanced Raman Scattering Imaging of Two-Dimensional Tungsten Disulfide with Optimized Tip Fabrication Process

We successfully achieve the tip-enhanced nano Raman scattering images of a tungsten disulfide monolayer with optimizing a fabrication method of gold nanotip by controlling the concentration of etchant in an electrochemical etching process. By applying a square-wave voltage supplied from an arbitrary waveform generator to a gold wire, which is immersed in a hydrochloric acid solution diluted with ethanol at various ratios, we find that both the conical angle and radius of curvature of the tip apex can be varied by changing the ratio of hydrochloric acid and ethanol. We also suggest a model to explain the origin of these variations in the tip shape. From the systematic study, we find an optimal condition for achieving the yield of similar to 60% with the radius of similar to 34 nm and the cone angle of similar to 35 degrees. Using representative tips fabricated under the optimal etching condition, we demonstrate the tip-enhanced Raman scattering experiment of tungsten disulfide monolayer grown by a chemical vapor deposition method with a spatial resolution of similar to 40 nm and a Raman enhancement factor of similar to 4,760. © The Author(s) 2017

Scutellaria baicalensis

Antimycin A (AMA) damages mitochondria by inhibiting mitochondrial electron transport and can produce reactive oxygen species (ROS). ROS formation, aging, and reduction of mitochondrial biogenesis contribute to mitochondrial dysfunction. The present study sought to investigate extracts of Scutellaria baicalensis and its flavonoids (baicalin, baicalein, and wogonin), whether they could protect mitochondria against oxidative damage. The viability of L6 cells treated with AMA increased in the presence of flavonoids and extracts of S. baicalensis. ATP production decreased in the AMA treated group, but increased by 50% in cells treated with flavonoids (except wogonin) and extracts of S. baicalensis compared to AMA-treated group. AMA treatment caused a significant reduction (depolarized) in mitochondrial membrane potential (MMP), whereas flavonoid treatment induced a significant increase in MMP. Mitochondrial superoxide levels increased in AMA treated cells, whereas its levels decreased when cells were treated with flavonoids or extracts of S. baicalensis. L6 cells treated with flavonoids and extracts of S. baicalensis increased their levels of protein expression compared with AMA-treated cells, especially water extracts performed the highest levels of protein expression. These results suggest that the S. baicalensis extracts and flavonoids protect against AMA-induced mitochondrial dysfunction by increasing ATP production, upregulating MMP, and enhancing mitochondrial function

Factors Affecting Endoscopic Curative Resection of Gastric Cancer in the Population-Based Screening Era

Background/Aims Since population-based screening for gastric cancer in Korea was implemented, endoscopic treatment of early gastric cancer has become increasingly popular. This study investigates factors affecting endoscopic curative resection of early gastric cancer in population-based screening for gastric cancer. Methods We retrospectively reviewed data of patients with newly diagnosed gastric cancer who underwent treatment at Seoul St. Mary’s Hospital. All patients completed questionnaires about clinical information, including interval between surveillance tests for gastric cancer. Results Of 469 gastric cancer patients, 147 (31.3%) had undergone curative endoscopic resection, 260 (55.4%) had undergone curative surgical resection, and 62 (13.3%) underwent non-curative resection or were in an inoperable state. Patients with curative endoscopic resection had fewer alarm symptoms/signs than other groups. In multivariate analysis, regular surveillance endoscopy was the only factor predicting curative endoscopic resection (odds ratio [OR], 6.099; 95% confidence interval [CI], 2.532–14.933). In addition, patients undergoing gastric cancer screening had a significantly higher rate of endoscopic curative resection compared with subjects who had never been screened. (1-year interval: OR, 49.969; 95% CI, 6.340–393.827, 2-year interval: OR, 15.283; 95% CI, 1.833–127.406, over 2-year interval: OR, 10.651; 95% CI, 1.248–90.871). Shorter screening test intervals were associated with higher rates of endoscopic curative resection. Conclusions Regular surveillance testing was the independent factor predicting curative endoscopic resection of gastric cancer

Identification of Factors that Influence Conscious Sedation in Gastrointestinal Endoscopy

Although several studies examined factors that influence conscious sedation, investigation was limited into the gender and age. The aim of this prospective study is to identify the clinical variables of successful conscious sedation during gastrointestinal endoscopy. A total of 300 subjects who underwent gastrointestinal endoscopy were enrolled in a prospective fashion. They completed a questionnaire to assess height, weight, drinking, smoking, education level, recent medication, past medical history, previous experience of conscious sedation, preprocedural anxiety, and apprehension about the procedure. Efficacy of sedation and amnesia were evaluated by the subject and the endoscopist. Amnesic and sedative effects were proportionally related with age (p<0.0001). Preprocedural anxiety level was higher in women (p=0.0062), younger subjects (p=0.035), slender subjects (p=0.041), and in those without previous experience of conscious sedation (p=0.0034). This anxiety level was also related to increased pain (p=0.0026) and alertness (p=0.0003) during the procedure. Lower dose of midazolam is needed for sedation in older subjects. Subjects with a high level of preprocedural anxiety such as women, younger subjects, slender subjects, and those without previous experience of conscious sedation should be sedated with great caution because generally, they complain of much more severe pain and alertness during the procedure

Correlation between blood, physiological and behavioral parameters in beef calves under heat stress

Objective The performance, health, and behaviour of cattle can be strongly affected by climate. The objective of this study was to determine the effect of heat stress on blood parameters, blood proteins (haptoglobin [Hp]; heat shock protein 70 [HSP70]), rectal temperature (RT), heart rate (HR) and rumination time in Korean native beef calves. Methods Thirty-two Korean native beef calves were randomly assigned to 8 groups with 4 animals per group. They were kept in environmental condition with temperature-humidity index (THI) ranging from 70.01 to 87.72 in temperature-humidity controlled chamber for 7 days. Results Their HR, RT, and serum cortisol and HSP70 levels were increased (p<0.05) in high THI compared to those at low THI. But, serum Hp level was decreased (p<0.05) in high THI compared to these at low THI. In addition, HR, RT, serum cortisol and HSP70 were positively correlated with THI (R2 = 0.8368, p<0.01; R2 = 0.6162, p<0.01; R2 = 0.581, p<0.01; R2 = 0.2241, p = 0.0062, respectively). There was also positive association between HR and cortisol (R2 = 0.4697, p<0.01). Similarly, RT and cortisol were positively associated (R2 = 0.4581, p<0.01). But, THI and HR were negatively correlated with Hp (R2 = 0.2157, p = 0.02; R2 = 0.3362, p = 0.003). Hematology and metabolites results were different among treatment groups. Standing position was higher (p<0.05) in the high THI group compared to that in the low THI group. Conclusion Based on these results, it can be concluded that HR, RT, blood parameters (Cortisol, HSP70, Hp) and standing position are closely associated with heat stress. These parameters can be consolidated to develop THI chart for Korean native beef calves