Synergistic effect of imp/ostA and msbA in hydrophobic drug resistance of Helicobacter pylori

<p>Abstract</p> <p>Background</p> <p>Contamination of endoscopy equipment by <it>Helicobacter pylori </it>(<it>H. pylori</it>) frequently occurs after endoscopic examination of <it>H. pylori</it>-infected patients. In the hospital, manual pre-cleaning and soaking in glutaraldehyde is an important process to disinfect endoscopes. However, this might not be sufficient to remove <it>H. pylori </it>completely, and some glutaraldehyde-resistant bacteria might survive and be passed to the next patient undergoing endoscopic examination through unidentified mechanisms. We identified an Imp/OstA protein associated with glutaraldehyde resistance in a clinical strain, NTUH-C1, from our previous study. To better understand and manage the problem of glutaraldehyde resistance, we further investigated its mechanism.</p> <p>Results</p> <p>The minimal inhibitory concentrations (MICs) of glutaraldehyde andexpression of <it>imp/ostA </it>RNA in 11 clinical isolates from the National Taiwan University Hospital were determined. After glutaraldehyde treatment, RNA expression in the strains with the MICs of 4–10 μg/ml was higher than that in strains with the MICs of 1–3 μg/ml. We examined the full-genome expression of strain NTUH-S1 after glutaraldehyde treatment using a microarray and found that 40 genes were upregulated and 31 genes were downregulated. Among the upregulated genes, <it>imp/ostA </it>and <it>msbA</it>, two putative lipopolysaccharide biogenesis genes, were selected for further characterization. The sensitivity to glutaraldehyde or hydrophobic drugs increased in both of <it>imp/ostA </it>and <it>msbA </it>single mutants. The <it>imp/ostA </it>and <it>msbA </it>double mutant was also hypersensitive to these chemicals. The lipopolysaccharide contents decreased in individual <it>imp/ostA </it>and <it>msbA </it>mutants and dramatically reduced in the <it>imp/ostA </it>and <it>msbA </it>double mutant. Outer membrane permeability assay demonstrated that the <it>imp/ostA </it>and <it>msbA </it>double mutation resulted in the increase of outer membrane permeability. Ethidium bromide accumulation assay demonstrated that MsbA was involved in efflux of hydrophobic drugs.</p> <p>Conclusion</p> <p>The expression levels of <it>imp/ostA </it>and <it>msbA </it>were correlated with glutaraldehyde resistance in clinical isolates after glutaraldehyde treatment. Imp/OstA and MsbA play a synergistic role in hydrophobic drugs resistance and lipopolysaccharide biogenesis in <it>H. pylori</it>.</p

The Influence of Court Surfaces on Lower Limb Muscle Activation of Tennis Run-and-Stroke

This study aimed to examine the characteristics of lower extremity muscle activity between different tennis court surfaces. Six male right-handed elite tennis players were recruited, and their electromyography activity (EMG) during open stance running forehand were collected. Average activity level of rectus femoris (RF), biceps femoris (BF), gastrocnemius (GAS), tibialis anterior (TA) from the lead leg, which normalized by maximal voluntary isometric contractions (MVC) was recorded under different situation (hard court, grass court, clay court). Our study demonstrates that GAS was significantly different and the activation level was greater on a hard court than on clay (p = .005). Tennis players should enhance their gastrocnemius muscle performance when matching from clay to hard court to avoid a higher level of gastrocnemius activation when adapting to a different court, which could lead to an injury. KEYWORDS: Grand Slam, training, EMG, performanc

KINEMATICS ANALYSIS OF THE UPPER EXTREMITY DURING THE TWOHANDED BACKHAND DRIVE VOLLEY FOR FEMALE TENNIS PLAYERS

The purpose of this study was to discuss the motion characteristics of the arms in the two-handed backhand drive volley. Five elite female tennis players participated in this study, their two-handed backhand drive volley strokes were analysed, and all participants are right handed. Motion Analysis System with 10 Eagle Digital inferred high speed cameras at 200Hz were used for this study. The results show a similar elbow and wrist speed strategy in x-axis between two-handed ground stroke and drive volley, our study also found that the rear arm dominates the stroke and mainly provide the topspin that is required for the skill of the drive volley. In order to create better stroke efficiency, the right elbow reached peak velocity first, followed by the right wrist before racket impact with the ball

Deterioration Estimation of Reinforced Concrete Building Structures Using Material Testing Data Base

This study aims to investigate the material factors that affect the degree of deterioration of reinforced concrete structures and develop an integrating evaluation model. Also, the durability indices were generated using the analytic hierarchy process for the overall durability assessment of structures, which corresponded to the durability grades referred as the maintenance, reinforcement, or demolishment. The status of concrete includes compressive strength, resistance coefficient, concrete cracks, honeycomb and spalling. And the reinforcement status includes corrosion potential, corrosion current, chloride ion content, neutralization depth and protective layer thickness. Durability indicators were determined through the findings on the structural inspection process of reinforced concrete structures and the evaluation methods related to materials testing and industry standards. Case studies were also presented to illustrate the methodology of the assessment system. The durability methodology can be summarized as the comprehensive evaluation methods considering the earthquake potential factors, structural factors, environmental factors, and material deterioration factors

Mass-accretion, spectral, and photometric properties of T Tauri stars in Taurus based on TESS and LAMOST

We present the analysis of 16 classical T Taur stars using LAMOST and TESS data, investigating spectral properties, photometric variations, and mass-accretion rates. All 16 stars exhibit emissions in H$\alpha$ lines, from which the average mass-accretion rate of $1.76\times10^{-9}~M_{\odot}yr^{-1}$ is derived. Two of the stars, DL Tau and Haro 6-13, show mass-accretion bursts simultaneously in TESS, ASAS-SN, and/or ZTF survey. Based on these observations, we find that the mass-accretion rates of DL Tau and Haro 6-13 reach their maximums of $2.5 \times 10^{-8}~M_{\odot}yr^{-1}$ and $2 \times 10^{-10}~M_{\odot}yr^{-1}$ during the TESS observation, respectively. We detect thirteen flares among these stars. The flare frequency distribution shows that the CTTSs' flare activity is not only dominated by strong flares with high energy but much more active than those of solar-type and young low-mass stars. By comparing the variability classes reported in the literature, we find that the transition timescale between different classes of variability in CTTSs, such as from Stochastic (S) to Bursting (B) or from quasi-periodic symmetric (QPS) to quasi-periodic dipping (QPD), may range from 1.6 to 4 years. We observe no significant correlation between inclination and mass-accretion rates derived from the emission indicators. This suggests that inner disk properties may be more important than that of outer disk. Finally, we find a relatively significant positive correlation between the asymmetric metric "M" and the cold disk inclination compared to the literature. A weak negative correlation between the periodicity metric "Q" value and inclination has been also found.Comment: 39 pages, 22 figures, 8 table

Therapeutic Strategies for Targeting IL-33/ST2 Signalling for the Treatment of Inflammatory Diseases

Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses via interaction with its receptor, ST2. Activation of ST2 signalling by IL-33 triggers pleiotropic immune functions in multiple ST2-expressing immune cells, including macrophages, neutrophils, eosinophils, basophils, mast cells, type 2 helper T cells, regulatory T cells, and group 2 innate lymphoid cells. IL-33-mediated effector functions contribute to the tissue inflammatory and reparative responses in various organs including lung, skin, kidney, central nerve system, cardiovascular system, and gastrointestinal system. Endogenous IL-33/ ST2 signaling exhibits diverse immune regulatory functions during progression of different diseases. IL-33 likely functions as a disease sensitizer and plays pathological roles in inflamed tissues in allergic disorders that involve hyperreactive immune responses in the context of skin and pulmonary allergy. However, IL-33 also mediates tissue-protective functions during the recovery phase following tissue injury in the central nerve system and gastrointestinal system. Modulation of the IL-33/ST2 axis, therefore, represents a promising strategy for treating immune disorders that involve dysregulation of the cytokine signalling. In the past two decades, therapeutic strategies blocking IL-33/ST2 have been extensively studied for the treatment of diseases in animal models. In this review, the current progress on the development of therapeutic biologics for targeting IL-33/ST2 signalling in inflammatory diseases is summarized

Bone-targeting agents in major solid tumour metastases: a multinational cohort study

OBJECTIVE: To describe the epidemiology, clinical characteristics and utilisation patterns of bone-targeting agents (BTAs) in patients with bone metastases from breast, prostate and lung cancer. METHODS: This is a multinational retrospective cohort study including patients with three major solid tumours (breast, prostate and lung cancer) and newly initiated on BTAs (ie, denosumab, zoledronic acid and pamidronate). Records were retrieved from nationwide health databases from Hong Kong and Taiwan (HK and TW: 2013–2017) and Korea (KR: 2012–2016). Descriptive analyses included the annual incidence rates of bone metastases and the cumulative incidence curves of BTA initiation. We used Sankey diagrams to visualise the dynamic BTA utilisation patterns. RESULTS: The annual incidence rate of bone metastases ranged from 3.5% to 4.5% in TW, from 9.6% to 10.3% in HK and from 2.9% to 3.8% in KR. We identified 14.1% (5127), 9.3% (883) and 9.4% (4800) of patients with bone metastases newly initiated on BTAs in TW, HK and KR, respectively. The most frequently used BTA in TW (67.1%) and HK (51.9%) was denosumab, while in KR (84.8%) it was zoledronic acid. Sankey diagrams indicated the proportion of patients remaining on denosumab was highest in TW and HK, while it was zoledronic acid in KR. Specifically, in TW, patients who were on bisphosphonates or had discontinued treatment frequently switched to or reinitiated denosumab. CONCLUSIONS: We found the rate of BTA utilisation remained low across all sites and tumour types in recent years. The dynamic utilisation patterns of BTAs provide better understanding of the treatment landscape for future evaluation of associated outcomes of patients

Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction

<p>Abstract</p> <p>Background</p> <p>Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR) injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury.</p> <p>Methods</p> <p>Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus immediate intra-renal administration of 1.0 × 10⁶autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR). The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed.</p> <p>Results</p> <p>Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p < 0.03). The mRNA expressions of inflammatory, oxidative stress, and apoptotic biomarkers were lower, whereas the anti-inflammatory, anti-oxidative, and anti-apoptotic biomarkers were higher in group 3 than in group 2 (all p < 0.03). Immunofluorescent staining showed a higher number of CD31+, von Willebrand Factor+, and heme oxygenase (HO)-1+ cells in group 3 than in group 2 (all p < 0.05). Western blot showed notably higher NAD(P)H quinone oxidoreductase 1 and HO-1 activities, two indicators of anti-oxidative capacity, in group 3 than those in group 2 (all p < 0.04). Immunohistochemical staining showed higher glutathione peroxidase and glutathione reductase activities in group 3 than in group 2 (all p < 0.02)</p> <p>Conclusion</p> <p>ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.</p

Intra-coronary administration of tacrolimus markedly attenuates infarct size and preserves heart function in porcine myocardial infarction

BACKGROUND: We test the hypothesis that intra-coronary tacrolimus administration can limit infarct size and preserve left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) through ligating left anterior descending coronary artery (LAD) in mini-pigs. METHODS: Twelve male mini-pigs were randomized into AMI-saline (MI-only) group and AMI-tacrolimus (MI-Tac) group that received intra-coronary saline (3.0 mL) and tacrolimus (0.5 mg in 2.5 mL saline) injection, respectively, beyond site of ligation 30 minutes after LAD occlusion. RESULTS: Larger infarct area was noted in MI-only group (p < 0.001). Inflammatory biomarkers at protein [oxidative stress, tumor necrotic factor-α, nuclear factor-κB], gene (matrix metalloproteinase-9, plasminogen activator inhibitor-1), and cellular (CD40+, CD68+ inflammatory cells) levels were remarkably higher in MI-only animals (p < 0.01). Conversely, anti-inflammatory biomarkers at gene level (Interleukin-10), gene and protein level (endothelial nitric oxide synthase), and anti-oxidant biomarkers at both gene and protein levels [heme oxygenase 1, NAD(P)H:quinone oxidoreductase] were lower in MI-only group (p < 0.01). Number of apoptotic nuclei and apoptotic biomarkers expressions at gene and protein levels (Bax, caspase 3) were notably higher, whereas anti-apoptotic biomarkers at gene and protein levels (Bcl-2), LVEF, and fractional shortening were markedly lower in MI-only group (p < 0.001). CONCLUSION: Intra-coronary administration of tacrolimus significantly attenuated infarct size and preserved LV function