Achiral Mannich-Base Curcumin Analogs Induce Unfolded Protein Response and Mitochondrial Membrane Depolarization in PANC-1 Cells.

Achiral Mannich-type curcumin analogs have been synthetized and assayed for their cytotoxic activity. The anti-proliferative and cytotoxic activity of curcuminoids has been tested on human non-small-cell lung carcinoma (A549), hepatocellular carcinoma (HepG2) and pancreatic cancer cell line (PANC-1). Based on the highest anti-proliferative activity nine drug candidates were further tested and proved to cause phosphatidylserine exposure as an early sign of apoptosis. Curcumin analogs with the highest apoptotic activity were selected for mechanistic studies in the most sensitive PANC-1 cells. Cytotoxic activity was accompanied by cytostatic effect since curcumin and analogs treatment led to G0/G1 cell cycle arrest. Moreover, cytotoxic effect could be also detected via the accumulation of curcuminoids in the endoplasmic reticulum (ER) and the up-regulation of ER stress-related unfolded protein response (UPR) genes: HSPA5, ATF4, XBP1, and DDIT3. The activated UPR induced mitochondrial membrane depolarization, caspase-3 activation and subsequent DNA breakdown in PANC-1 cells. Achiral curcumin analogs, C509, C521 and C524 possessed superior, 40-times more potent cytotoxic activity compared to natural dihydroxy-dimetoxycurcumin in PANC-1 cells.

Work Motivation: A Wall That Not Even the COVID-19 Pandemic Could Knock Down: Research Article.

The emergence of the coronavirus pandemic in 2020 posed a new challenge, imposing extraordinary physical and psychological burdens on healthcare workers, clearly exacerbating and intensifying career abandonment. Objectives: The aim of our study was to explore the motivating factors among nurses serving during the coronavirus pandemic that they considered important in their profession despite the mental and physical stress brought about by the pandemic. Methods: A descriptive, cross-sectional study was conducted at the University of Pécs-Clinical Center-Regional Coronavirus Care Center between September 2022 and December 2022. We used non-random, expert, purposive sampling, recruiting healthcare workers who had spent at least 3 months working in a COVID ward (n = 196). Data collection was conducted by using an online, anonymous questionnaire, which included sociodemographic questions, the "Motivation at Work Scale", and a self-edited six-item questionnaire. Results: Regarding the 5-year probability of remaining in the healthcare field, nine participants (4.5%) will definitely leave the healthcare sector, twenty-seven participants (13.7%) are undecided, and seventy-eight participants (39.7%) will definitely stay in the healthcare field over the next 5 years. There is a positive, weak, but significant correlation between intrinsic motivation and the probability of leaving the profession within 5 years (r = 0.281; p < 0.05). We identified a significant, negative, and weak correlation between the number of revisited waves of the coronavirus and the fear of redeployment to the COVID ward (r = -0.273; p < 0.05). Conclusions: Despite the challenges posed by the coronavirus pandemic, only a small percentage of nurses consider leaving the healthcare profession. Joy and enjoyment in their work were dominant factors even during the pandemic.