Conectar
by Dino Bekric, Tobias Kiesslich, Matthias Ocker, Martina Winklmayr, Markus Ritter, Heidemarie Dobias, Marlena Beyreis, Daniel Neureiter, Christian Mayr
IntroductionBiliary tract cancer (BTC) is a lethal disease with a bad overall survivability, partly arising from inadequate therapeutic alternatives, detection at a belated stage, and a resistance to common therapeutic approaches. Ferroptosis is a form of programmed cell death that depends on reactive oxygen species (ROS) and iron, causing excessive peroxidation of polyunsaturated fatty acids (PUFAs). Therefore, the objective of this investigation is, whether ferroptosis can be induced in BTC in vitro and whether this induction is dependent on specific molecular markers.
MethodsThe study conducted resazurin assay and IC25/50 calculation to explore the possible cytotoxic outcomes of different classes of ferroptosis-inducing substances (FINs) on a comprehensive in vitro model of 11 BTC cell lines. Combinatory treatments with different cell death inhibitors were performed to evaluate the magnitude of ferroptosis induction. To ascertain whether ferroptotic cell death occurred, liperfluo and iron assay kits were employed to evaluate lipid ROS and intracellular iron abundance. Potential biomarkers of ferroptosis sensitivity were then assessed via western blot analysis, a rtPCR panel and functional assay kits.
ResultsThe study found that different FINs reduced cell viability in a cell line-dependent manner. In addition, we measured increased lipid ROS and intracellular Fe2+ levels upon exposure to FINs in BTC cells. Combining FINs with inhibitors of ferroptosis, necroptosis or apoptosis suggests the occurrence of ferroptotic events in BTC cell lines CCC-5, HuH-28 and KKU-055. Furthermore, we found that BTC cells display a heterogeneous profile regarding different molecular genes/markers of ferroptosis. Subsequent analysis revealed that sensitivity of BTC cells towards IKE and RSL3 positively correlated with CD71 and SLC7A11 protein expression.
ConclusionOur results demonstrate that induction of ferroptosis is a promising approach to inhibit BTC cell growth and that the sensitivity of BTC cells towards ferroptosis induction might be dependent on molecular markers such as CD71 and SLC7A11.
Mental health and well-being of healthcare staff were majorly impacted by the COVID-19 pandemic. Little attention has been devoted to the role employers could choose to play in mitigating long-term negative consequences and how effective organisational measures taken were perceived by the individual healthcare workers. This study aims to investigate (1) whether and how healthcare professionals’ mental health has changed from the second to the third pandemic year, (2) whether differences between professional groups (physicians, nurses, paramedics) identified in previous studies persisted and (3) how job demands and resources, for example, work culture and employers’ measures, impacted this situation.
The study employs an observational, cross-sectional design, using an online survey.
The study was conducted online from mid-June to mid-August 2022 among healthcare staff in state-run and private healthcare facilities, such as doctor’s practices, hospitals and paramedic organisations, in Germany and Austria (n=421).
We measured psychological strain using an ICD-10-based symptom checklist, as well as subjective strain and importance of stressors using self-report questions. The ICD-10 was the 10th version of the International Statistical Classification of Diseases and Related Health Problems, a widely used standardized diagnostic manual.
Psychological strain stayed relatively consistent, with nursing staff suffering the most. While the job demands participants felt most affected by were structural issues (eg, staff shortages), employers were far more likely to be perceived as taking action against pandemic-specific job demands (eg, lack of protective gear). Psychological strain was lowest when staff perceived employers’ actions as effective. Only 60% of those with severe enough symptoms to require psychological help had intentions of seeking such help, which is in line with past studies. This help-seeking hesitancy was also dependent on different facets of perceived work culture.
Healthcare staff and nursing staff in particular continue to suffer in the aftermath of the COVID-19 pandemic. However, while employers were perceived as taking action against pandemic-specific job demands, pre-existing job demands causing stress and psychological strain for staff have remained uncombatted.
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