Apoptosis signal-regulating kinase 1 mediates denbinobin-induced apoptosis in human lung adenocarcinoma cells

In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1) in denbinobin-induced apoptosis in human lung adenocarcinoma (A549) cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN), two antioxidants (N-acetyl-L-cysteine (NAC) and glutathione (GSH)), a c-Jun N-terminal kinase (JNK) inhibitor (SP600125), and an activator protein-1 (AP-1) inhibitor (curcumin). Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS) production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis

Antimicrobial Activity of Lactobacillus Species Against Carbapenem-Resistant Enterobacteriaceae

ObjectiveThis study aims to identify suitable lactobacilli that have anti-carbapenem-resistant Enterobacteriaceae (CRE) activity with in vitro tolerance to pepsin and bile salts.MethodsFifty-seven Lactobacillus spp. strains encompassing nine species were collected for investigation. Their viabilities in the presence of pepsin and bile salts were tested using tolerance tests. Their anti-CRE effects were assessed by agar well diffusion and broth microdilution assay, as well as time-kill test.ResultsOf the 57 Lactobacillus isolates collected, 31 had a less than 2-log reduction in their viability in both pepsin and bile salt tolerance tests. Of these 31 isolates, 5 (LUC0180, LUC0219, LYC0289, LYC0413, and LYC1031) displayed the greatest anti-CRE activity with a CRE zone of inhibition greater than 15 mm in agar well diffusion assays. The minimal inhibitory percentages of supernatants from these five strains against CREs ranged from 10 to 30%. With the exception of LUC0180, which had a minimal bactericidal percentage ≥ 40%, the bactericidal percentage of all the strains ranged from 20 to 40%. The inhibitory effect of the cell-free culture supernatants from these Lactobacillus strains did not change after heating but was abolished as the pH changed to 7.0. After a 24-h incubation, five of the Lactobacillus strains at a concentration of 108 CFU/ml totally inhibited the growth of carbapenem-resistant Escherichia coli (CRE316) and Klebsiella pneumoniae (CRE632). After a 48-h incubation, the growth of CRE316 was completely inhibited under each concentration of lactobacilli based on time-kill test. Furthermore, when the concentration of lactobacilli was at 108 CFU/ml, the decline in pH was faster than at other concentrations.ConclusionSome Lactobacillus strains exhibit anti-CRE activity, which suggests potential applications for controlling or preventing CRE colonization or infection

Fully Automated Quantification of the Striatal Uptake Ratio of [99mTc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson’s Disease and the Temporal Regression of Striatal Tracer Uptake

Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [Tc99m]-TRODAT with SPECT imaging. Procedures. A normal [Tc99m]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n=365) and nPD subjects (28 healthy controls and 33 essential tremor patients) were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs) and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR). The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC) analysis. Results. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC) of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R2=0.84. Conclusions. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients

The Roles of Social Support and Health Literacy in Self-Management Among Patients With Chronic Kidney Disease

[[abstract]]Aims: To investigate the relationships among social support, health literacy, and self-management, and the factors influencing self-management of chronic kidney disease (CKD). Design: Cross-sectional study. Methods: A random sample of 410 patients was recruited from nephrology clinics. Data were collected using structured questionnaires and chart reviews from January 2013 to February 2014. Hierarchical regression analysis was used to determine the predictive factors of self-management behaviors and ∆R2 to determine each variable's explanatory power. Findings: Health literacy and social support were positively correlated with self-management behaviors. Furthermore, social support, health literacy, and marital status were significant predictors of self-management behaviors. Social support had a relatively greater explanatory power for self-management behaviors than did health literacy. Particularly, healthcare provider support had the greatest influence on patients' self-management behaviors. Conclusions: Health literacy and social support play independent positive roles in self-management behaviors of patients with CKD, with social support having a particularly dominant role. Further research using a systems approach to improving self-management behaviors is necessary to clarify the role of social support. Clinical relevance: Health literacy and social support are independently and positively related to self-management. Social support, which is a system-level factor, is a relatively stronger and crucial predictor than is health literacy. Nurses have to refine self-management programs to focus on families and adopt a systems approach to help CKD patients improve their self-management behaviors

The Impact of Hepatitis C Virus, Metabolic Disturbance, and Unhealthy Behavior on Chronic Kidney Disease: A Secondary Cross-Sectional Analysis

Background: Hepatitis C virus (HCV) infection is associated with a higher risk of chronic kidney disease (CKD). This study investigates the relationship among HCV, CKD, and understudied confounders, such as unhealthy behaviors and metabolic disturbances. Methods: This cross-sectional study was conducted as part of a community health promotion program in an HCV endemic area of Taiwan from June to December 2019. Multivariable logistic regression analyses adjusted for demographic and clinical characteristics were performed to investigate the association between CKD and HCV seropositivity. Results: Of 2387 participants who underwent health check-ups, the mean age was 64.1 years old; females predominated (63.2%), and 306 (12.8%) subjects were seropositive for HCV. CKD, defined as a lower estimated glomerular filtration rate (eGFR) was associated with unhealthy dietary habits, metabolic syndrome, and HCV. Less frequent exercise, higher waist circumference (WC) and HbA1c all affected risk of CKD; HCV increased risk of CKD by 44% compared to non-HCV (OR 1.44, 95% confidence interval (CI) 1.05–1.98) in the multivariable analysis. In the HCV group, lower eGFR was also significantly associated with the severity of metabolic syndrome (MetS) (median eGFR was 86.4, 77.1, and 64.5 mL/min/1.73 m2 for individuals with three and five MetS components, respectively). Conclusions: Beyond metabolic disturbance and irregular exercise, HCV seropositivity is independently associated with CKD in a community survey. Healthy lifestyle promotion might protect against renal function decline in HCV; however, the mechanisms underlying the association need further large-scale investigation

Trend of RA assessment effects under different diagnosis record numbers.

<p>Trend of RA assessment effects under different diagnosis record numbers.</p