IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major nosocomial pathogen that is widespread in both health-care facilities and in the community at large, as a result of direct host-to-host transmission. Several virulence factors are associated with pathogen transmission to naive hosts. Immunodominant surface antigen B (IsaB) is a virulence factor that helps Staphylococcus aureus to evade the host defense system. However, the mechanism of IsaB on host transmissibility remains unclear. We found that IsaB expression was elevated in transmissible MRSA. Wild-type isaB strains inhibited autophagic flux to promote bacterial survival and elicit inflammation in THP-1 cells and mouse skin. MRSA isolates with increased IsaB expression showed decreased autophagic flux, and the MRSA isolate with the lowest IsaB expression showed increased autophagic flux. In addition, recombinant IsaB rescued the virulence of the isaB deletion strain and increased the group A streptococcus (GAS) virulence in vivo. Together, these results reveal that IsaB diminishes autophagic flux, thereby allowing MRSA to evade host degradation. These findings suggest that IsaB is a suitable target for preventing or treating MRSA infection

Antcin K, a Triterpenoid Compound from Antrodia camphorata

The purpose of this study was to screen firstly the potential effects of antcin K (AnK), the main constituent of the fruiting body of Antrodia camphorata, in vitro and further evaluate the activities and mechanisms in high-fat-diet- (HFD-) induced mice. Following 8-week HFD-induction, mice were treated with AnK, fenofibrate (Feno), metformin (Metf), or vehicle for 4 weeks afterward. In C2C12 myotube cells, the membrane GLUT4 and phospho-Akt expressions were higher in insulin and AnK-treated groups than in the control group. It was observed that AnK-treated mice significantly lowered blood glucose, triglyceride, total cholesterol, and leptin levels in AnK-treated groups. Of interest, AnK at 40 mg/kg/day dosage displayed both antihyperglycemic effect comparable to Metf (300 mg/kg/day) and antihypertriglyceridemic effect comparable to Feno (250 mg/kg/day). The combination of significantly increased skeletal muscular membrane expression levels of glucose transporter 4 (GLUT4) but decreased hepatic glucose-6-phosphatase (G6 Pase) mRNA levels by AnK thus contributed to a decrease in blood glucose levels. Furthermore, AnK enhanced phosphorylation of AMP-activated protein kinase (phospho-AMPK) expressions in the muscle and liver. Moreover, AnK treatment exhibited inhibition of hepatic fatty acid synthase (FAS) but enhancement of fatty acid oxidation peroxisome proliferator-activated receptor α (PPARα) expression coincident with reduced sterol response element binding protein-1c (SREBP-1c) mRNA levels in the liver may contribute to decreased plasma triglycerides, hepatic steatosis, and total cholesterol levels. The present findings indicate that AnK displays an advantageous therapeutic potential for the management of type 2 diabetes and hyperlipidemia

Deferoxamine retinopathy: spectral domain-optical coherence tomography findings

Al-Djamiʿ li Ibn al-BaïtharNumérisation effectuée à partir d'un document de substitution

Deferoxamine retinopathy: spectral domain-optical coherence tomography findings

BACKGROUND: To describe the spectral domain optical coherence tomography (SD-OCT) findings of a patient who developed pigmentary retinopathy following high-dose deferoxamine administration. CASE PRESENTATION: A 34-year-old man with thalassemia major complained of nyctalopia and decreased vision following high-dose intravenous deferoxamine to treat systemic iron overload. Fundus examination revealed multiple discrete hypo-pigmented lesions at the posterior pole and mid-peripheral retina. Recovery was partial following cessation of desferrioxamine six weeks later. A follow-up SD-OCT showed multiple accumulated hyper-reflective deposits primarily in the choroid, retina pigment epithelium (RPE), and inner segment and outer segment (IS/OS) junction. CONCLUSION: Deferoxamine retinopathy primarily targets the RPE–Bruch membrane–photoreceptor complex, extending from the peri-fovea to the peripheral retina with foveola sparing. An SD-OCT examination can serve as a simple, noninvasive tool for early detection and long-term follow-up

Matrix metalloproteinase-3 promoter polymorphisms but not dupA-H. pylori correlate to duodenal ulcers in H. pylori-infected females

<p>Abstract</p> <p>Background</p> <p>This study investigated if the <it>H. pylori dupA </it>genotype and certain host single nucleotide polymorphisms (SNPs) of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), including MMP-3, MMP-7, MMP-9, TIMP-1 and TIMP-2, might correlate with ulcer risk of <it>H. pylori-</it>infected Taiwanese patients.</p> <p>Results</p> <p>Of the 549 <it>H. pylori-</it>infected patients enrolled, 470 patients (265 with gastritis, 118 with duodenal ulcer, and 87 with gastric ulcer) received SNPs analysis of MMP-3_{-1612 6A > 5A}, MMP-7_{-181 A > G}, MMP-9_{exon 6 A > G}, TIMP-1_{372 T > C}and TIMP-2_{-418 G > C}by PCR-RFLP. The 181 collected <it>H. pylori </it>isolates were detected for the <it>dupA </it>genotype by PCR. The rates of <it>dupA</it>-positive <it>H. pylori </it>infection were similar among patients with duodenal ulcer (22.8%), gastric ulcer (20.0%), and gastritis (25.5%) (<it>p </it>> 0.05). Males had higher rates of duodenal ulcer and gastric ulcer than females (<it>p </it>< 0.01). Of <it>H. pylori</it>-infected patients, the MMP-3 6A6A genotype were more common in patients with duodenal ulcers than in those with gastritis (87.7% <it>vs</it>. 74.9%, <it>p </it>< 0.05) in females. This genotype had a 2.4-fold (95% CI: 1.02-5.66) increased risk of duodenal ulcer, compared to those with the 5A carrier. Combining the MMP-3/TIMP-1 genotype as 6A6A/CC, the risk of duodenal ulcer increased up to 3.6 fold (<it>p </it>< 0.05) in <it>H. pylori-</it>infected females.</p> <p>Conclusions</p> <p>The MMP-3 promoter polymorphism, but not the <it>dupA</it>-status, may correlate with susceptibility to duodenal ulcer after <it>H. pylori </it>infection in Taiwanese females.</p

Topological surface electronic states in candidate nodal-line semimetal CaAgAs

We investigate systematically the bulk and surface electronic structure of the candidate nodal-line semimetal CaAgAs by angle resolved photoemission spectroscopy and density functional calculations. We observed a metallic, linear, non-$k_z$-dispersive surface band that coincides with the high-binding-energy part of the theoretical topological surface state, proving the topological nontriviality of the system. An overall downshift of the experimental Fermi level points to a rigid-band-like $p$-doping of the samples, due possibly to Ag vacancies in the as-grown crystals.Comment: 6 pages, 5 figure

Persistent Tissue Kinetics and Redistribution of Nanoparticles, Quantum Dot 705, in Mice: ICP-MS Quantitative Assessment

Background: Quantum dots (QDs) are autofluorescent semiconductor nanocrystals that can be used for in vivo biomedical imaging. However, we know little about their in vivo disposition and health consequences. Objectives: We assessed the tissue disposition and pharmacokinetics of QD705 in mice. Methods: We determined quantitatively the blood and tissue kinetics of QD705 in mice after single intravenous (iv) injection at the dose of 40 pmol for up to 28 days. Inductively coupled plasma–mass spectrometry (ICP-MS) measurement of cadmium was the primary method of quantification of QD705. Fluorescence light microscopy revealed the localization of QD705 in tissues. Results: Plasma half-life of QD705 in mice was short (18.5 hr), but ICP-MS analyses revealed QD705 persisted and even continued to increase in the spleen, liver, and kidney 28 days after an iv dose. Considerable time-dependent redistribution from body mass to liver and kidney was apparent between 1 and 28 days postdosing. The recoveries at both time points were near 100%; all QD705s reside in the body. Neither fecal nor urinary excretion of QD705 was detected appreciably in 28 days postdosing. Fluorescence microscopy demonstrated deposition of QD705 in the liver, spleen, and kidneys. Conclusion: Judging from the continued increase in the liver (29–42% of the administered dose), kidney (1.5–9.2%), and spleen (4.8–5.2%) between 1 and 28 days without any appreciable excretion, QD705 has a very long half-life, potentially weeks or even months, in the body and its health consequences deserve serious consideration