Resveratrol Downregulates Interleukin-6-Stimulated Sonic Hedgehog Signaling in Human Acute Myeloid Leukemia

IL-6 and sonic hedgehog (Shh) signaling molecules are considered to maintain the growth of cancer stem cells (CSCs). Resveratrol, an important integrant in traditional Chinese medicine, possesses certain antitumor effects. However, the mechanisms on regulating acute myeloid leukemia (AML) are unclear. This study first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1β in AML patients were higher and lower, respectively, than healthy donors. The expression of Shh preproproteins, and C- and N-terminal Shh peptides increased in bone marrow and peripheral blood mononuclear cells isolated from AML patients, and the plasma N-Shh secretion was greater. To further clarify the effect of IL-6 and resveratrol in Shh signaling, human AML HL-60 cells were tested. IL-6 upregulated Shh and Gli-1 expression and was accompanied by an increase of cell viability. Resveratrol significantly decreased CSC-related Shh expression, Gli-1 nuclear translocation, and cell viability in IL-6-treated HL-60 cells and had synergistic effect with Shh inhibitor cyclopamine on inhibiting cell growth. Conclusions. IL-6 stimulated the growth of AML cells through Shh signaling, and this effect might be blocked by resveratrol. Further investigations of Shh as a prognostic marker and resveratrol as a therapeutic drug target to CSCs in AML are surely warranted

Epinephrine administration via a laryngeal mask airway: what is the optimal dose?

Background. The aim of this animal study was to clarify the effects of laryngeal mask airway (LMA)-administrated epinephrine and to assess the optimal dose. Methods. Thirty pigs were anesthetized and intubated with a cuffed tracheal tube (TT) and an LMA. Then they were assigned to one of five groups. The control group received distilled water 10 mL via the TT; the TT group received epinephrine 50 μg/kg via the TT; and the other three groups received two, four or six times the TT dose of epinephrine via the LMA. Heart rate (HR) and arterial pressure were monitored before and after drug administration for 15 minutes. Results. After epinephrine administration, the LMA-6 and TT groups had elevated systolic, diastolic and mean arterial pressures at 1 min and there was no significant difference between the two groups. In the TT group, these parameters peaked at 2 min then declined rapidly. In the LMA-6 group, they increased more slowly, and then maintained a plateau. The control, LMA-2 and LMA-4 groups failed to display significant persistent (>2 min) hemodynamic changes. Conclusions. We could not identify an optimal LMA-administrated epinephrine dose. The TT route is suitable when a high peak drug effect is required and the LMA route may be preferable if a persistent plateau effect is desired. Effective LMA administration of drugs may require larger doses than those given via TT

Lessons Learned of NSPO’s Picosatellite Mission: Yamsat - 1A, 1B & 1C

The YamSat is the first developed picosatellite in National Space Program Office’s (NSPO), Taiwan, R.O.C. It is scheduled to flight in the CubeSat launch in 2003. The rapid-prototyping system engineering different from the past formal discipline opens a new satellite development model in NSPO. The YamSat Test Readiness Review Meeting was successfully held in January 2002 and the environmental tests were completed by end March 2002. Besides the breadboard model and engineering test bed to prove of operation concept are built, three YamSats (1A, 1B, & 1C) instead of one are manufactured with slightly different configurations and purposes. The YamSat- 1A is for flight with ambitious and novel R.O.C. made components, including 15 domestic organizations and companies’ participation. The YamSat-1B is basically for backup purpose and demonstration, whereas the YamSat-1C is for amateur communication experiment end-to-end field test, and for public education purpose. This new experience gives fruitful lessons learned and provides low cost space experimentation and education to the next built picosatellites in Taiwan’s universities. Detailed mission and lessons learned are addressed in this paper

Correction: Wen-I Liao, et al. Ac2-26, an Annexin A1 Peptide, Attenuates Ischemia-Reperfusion-Induced Acute Lung Injury. Int. J. Mol. Sci. 2017, 18, 1771

The authors would like to make a correction to their published paper [1][...

Ac2-26, an Annexin A1 Peptide, Attenuates Ischemia-Reperfusion-Induced Acute Lung Injury

Annexin A1 (AnxA1) is an endogenous protein that modulates anti-inflammatory processes, and its therapeutic potential has been reported in a range of inflammatory diseases. The effect of AnxA1 on ischemia-reperfusion (IR)-induced lung injury has not been examined. In this study, isolated, perfused rat lungs were subjected to IR lung injury induced by ischemia for 40 min, followed by reperfusion for 60 min. The rat lungs were randomly treated with vehicle (phosphate-buffered saline), and Ac2-26 (an active N-terminal peptide of AnxA1) with or without an N-formyl peptide receptor (FPR) antagonist N-Boc-Phe-Leu-Phe-Leu-Phe (Boc2). An in vitro study of the effects of Ac2-26 on human alveolar epithelial cells subjected to hypoxia-reoxygenation was also investigated. Administration of Ac2-26 in IR lung injury produced a significant attenuation of lung edema, pro-inflammatory cytokine production recovered in bronchoalveolar lavage fluid, oxidative stress, apoptosis, neutrophil infiltration, and lung tissue injury. Ac2-26 also decreased AnxA1 protein expression, inhibited the activation of nuclear factor-κB and mitogen-activated protein kinase pathways in the injured lung tissue. Finally, treatment with Boc2 abolished the protective action of Ac2-26. The results indicated that Ac2-26 had a protective effect against acute lung injury induced by IR, which may be via the activation of the FPR

Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats

Abstract Background Emerging evidence reveals that nicotinamide phosphoribosyltransferase (NAMPT) has a significant role in the pathophysiology of the inflammatory process. NAMPT inhibition has a beneficial effect in the treatment of a variety of inflammatory diseases. However, it remains unclear whether NAMPT inhibition has an impact on ischemia-reperfusion (I/R)-induced acute lung injury. In this study, we examined whether NAMPT inhibition provided protection against I/R lung injury in rats. Methods Isolated perfused rat lungs were subjected to 40 min of ischemia followed by 60 min of reperfusion. The rats were randomly allotted to the control, control + FK866 (NAMPT inhibitor, 10 mg/kg), I/R, or I/R + FK866 groups (n = 6 per group). The effects of FK866 on human alveolar epithelial cells exposed to hypoxia-reoxygenation (H/R) were also investigated. Results Treatment with FK866 significantly attenuated the increases in lung edema, pulmonary arterial pressure, lung injury scores, and TNF-α, CINC-1, and IL-6 concentrations in bronchoalveolar lavage fluid in the I/R group. Malondialdehyde levels, carbonyl contents and MPO-positive cells in lung tissue were also significantly reduced by FK866. Additionally, FK866 mitigated I/R-stimulated degradation of IκB-α, nuclear translocation of NF-κB, Akt phosphorylation, activation of mitogen-activated protein kinase, and downregulated MKP-1 activity in the injured lung tissue. Furthermore, FK866 increased Bcl-2 and decreased caspase-3 activity in the I/R rat lungs. Comparably, the in vitro experiments showed that FK866 also inhibited IL-8 production and NF-κB activation in human alveolar epithelial cells exposed to H/R. Conclusions Our findings suggest that NAMPT inhibition may be a novel therapeutic approach for I/R-induced lung injury. The protective effects involve the suppression of multiple signal pathways

Down-regulation of partial substitution for staple food by oat noodles on blood lipid levels: A randomized, double-blind, clinical trial

This clinical trial was conducted to assess the lipid-lowering activity of oat noodles by replacing partial staple food (wheat or rice noodle) in normal and mildly hypercholesterolemic subjects. Totally 84 healthy and mild hypercholesterolemic subjects were recruited and divided into 2 groups as experimental (oat noodles) and placebo (wheat noodles) and instructed to consume 100 g of oat noodles or wheat noodles (replacing one or two meals/day) for 10 weeks and followed by 2 weeks of follow up (without noodle consumption). Various anthropometric measurements and biochemical analysis were carried out during initial (baseline), 2nd, 6th, 10th and 12th week (follow-up). Consumption of oat noodles by replacing staple food for 10 weeks significantly reduced (**p < 0.01) the levels of total cholesterol (TC; 17.46%) and low-density lipoprotein LDL-c (19.03%) in both healthy and mildly hypercholesterolemic subjects. However, the hypocholesterolemic effect is significantly higher in mildly hypercholesterolemic subjects as compared with normal subjects. A pronounced decline (*p < 0.05) in the levels of various cardiovascular diseases (CVDs) markers including TC/HDL and LDL/HDL ratios and blood pressure (SBP; 11.09% and DBP; 7.48%) were observed in oat noodles supplemented subjects as equivalence with the placebo group. The partial replacement of staple food with oat noodle could considerably improve the health status of all subjects especially in hypercholesterolemic subjects and thus lower the risk of CVDs. Keywords: Hypercholesterolemic, Oat noodles, Total cholesterol, Blood pressure, Staple foo