Examining the Impact of Job Satisfaction and Employee Engagement as Mediators between Job Crafting and Turnover Intention in Saudi Companies

This study aims to investigate the impact of Job Satisfaction and Employee Engagement as Mediators between Job Crafting and Turnover Intention. By Examining 190 private sector employees in Saudi Arabia and using linear regressions Analysis and validated questionnaire, the results of the study show that (1) There is a positive relationship between job crafting and job satisfaction, (2) Job crafting is a positively related to employee engagement.  Also (3) There is a positive relationship between job satisfaction and employee engagement. Whereas (4) Job satisfaction and turnover intention is negatively related to each other. Finally, it has been found that (5) There is a negative relationship between employee engagement and turnover intention. These findings suggest that the turnover intention of employees could be reduced through empowering employees by generating job-crafting behaviors. Thus, will lead eventually to job satisfaction and employee engagement. Keywords: job satisfaction, employee engagement, job crafting, turnover intention DOI: 10.7176/EJBM/13-7-09 Publication date: April 30th 202

Population pharmacokinetic modelling of indium-based quantum dot nanoparticles: preclinical in vivo studies

There is considerable interest in biomedical applications of quantum dot (QD) nanoparticles, in particular their use as imaging agents for diagnostic applications. In order to investigate the in vivo biodistribution and the potential toxicity of quantum dots (QDs), it is crucial to develop pharmacokinetic (PK) models as basis for prediction of QDs exposure profiles over time. Here, we investigated the in vivo biodistribution of novel indium-based QDs in mice for up to three months after intravenous administration and subsequently developed a translational population PK model to scale findings to humans. This evaluation was complemented by a comprehensive overview of the in vivo toxicology of QDs in rats. The QDs were primarily taken up by the liver and spleen and were excreted via hepatobiliary and urinary pathways. A non-linear mixed effects modelling approach was used to describe blood and organ disposition characteristics of QDs using a multi-compartment PK model. The observed blood and tissue exposure to QDs was characterised with an acceptable level of accuracy at short and long-term. Of note is the fast distribution of QDs from blood into liver and spleen in the first 24 h post-injection (half-life of 28 min) followed by a long elimination profile (half-life range: 47-90 days). This is the first study to assess the PK properties of QDs using a population pharmacokinetic approach to analyse in vivo preclinical data. No organ damage was observed following systemic administration of QDs at doses as high as 48 mg/kg at 24 h, 1 week and 5 weeks post-injection. In conjunction with the data arising from the toxicology experiments, PK parameter estimates provide insight into the potential PK properties of QDs in humans, which ultimately allow prediction of their disposition and enable optimisation of the design of first-in-human QDs studies

Uptake Rate of Cationic Mitochondrial Inhibitor MKT-077 Determines Cellular Oxygen Consumption Change in Carcinoma Cells

<div><h3>Objective</h3><p>Since tumor radiation response is oxygen-dependent, radiosensitivity can be enhanced by increasing tumor oxygenation. Theoretically, inhibiting cellular oxygen consumption is the most efficient way to increase oxygen levels. The cationic, rhodacyanine dye-analog MKT-077 inhibits mitochondrial respiration and could be an effective metabolic inhibitor. However, the relationship between cellular MKT-077 uptake and metabolic inhibition is unknown. We hypothesized that rat and human mammary carcinoma cells would take up MKT-077, causing a decrease in oxygen metabolism related to drug uptake.</p> <h3>Methods</h3><p>R3230Ac rat breast adenocarcinoma cells were exposed to MKT-077. Cellular MKT-077 concentration was quantified using spectroscopy, and oxygen consumption was measured using polarographic electrodes. MKT-077 uptake kinetics were modeled by accounting for uptake due to both the concentration and potential gradients across the plasma and mitochondrial membranes. These kinetic parameters were used to model the relationship between MKT-077 uptake and metabolic inhibition. MKT-077-induced changes in oxygen consumption were also characterized in MDA-MB231 human breast carcinoma cells.</p> <h3>Results</h3><p>Cells took up MKT-077 with a time constant of ∼1 hr, and modeling showed that over 90% of intracellular MKT-077 was bound or sequestered, likely by the mitochondria. The uptake resulted in a rapid decrease in oxygen consumption, with a time constant of ∼30 minutes. Surprisingly the change in oxygen consumption was proportional to uptake rate, not cellular concentration. MKT-077 proved a potent metabolic inhibitor, with dose-dependent decreases of 45–73% (p = 0.003).</p> <h3>Conclusions</h3><p>MKT-077 caused an uptake rate-dependent decrease in cellular metabolism, suggesting potential efficacy for increasing tumor oxygen levels and radiosensitivity <em>in vivo</em>.</p> </div

Sulforaphane Causes Epigenetic Repression of hTERT Expression in Human Breast Cancer Cell Lines

Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is a common dietary component that has histone deacetylase inhibition activity and exciting potential in cancer prevention. The mechanisms by which SFN imparts its chemopreventive properties are of considerable interest and little is known of its preventive potential for breast cancer. expression facilitated the induction of cellular apoptosis in human breast cancer cells.Collectively, our results provide novel insights into SFN-mediated epigenetic down-regulation of telomerase in breast cancer prevention and may open new avenues for approaches to SFN-mediated cancer prevention

Bioavailability of the Polyphenols: Status and Controversies

The current interest in polyphenols has been driven primarily by epidemiological studies. However, to establish conclusive evidence for the effectiveness of dietary polyphenols in disease prevention, it is useful to better define the bioavailability of the polyphenols, so that their biological activity can be evaluated. The bioavailability appears to differ greatly among the various phenolic compounds, and the most abundant ones in our diet are not necessarily those that have the best bioavailability profile. In the present review, we focus on the factors influencing the bioavailability of the polyphenols. Moreover, a critical overview on the difficulties and the controversies of the studies on the bioavailability is discussed