Anti-ovarian cancer potential, in silico studies, and anti-Alzheimer's disease effects of some natural compounds as cholinesterase inhibitors.

Ovarian cancer ranks seventh in the most common malignant tumors in females and seriously threatens women's reproductive health. Natural sources may lead to basic research on potential bioactive components as lead compounds in drug discovery and, ultimately, therapeutic treatments for ovarian cancer and other diseases. Alzheimer's disease (AD) and ovarian cancer are complex diseases of aging that impose an enormous public health burden worldwide. Additionally, people with AD have low levels of acetylcholine in their brains. Enzymes called cholinesterases break down acetylcholine in the brain. If their action is inhibited, more acetylcholine is available for communication among brain cells. In this study, pregnanolone, diethylstilbestrol (DES), flavokawain C, and methyl 3,4,5-trihydroxybenzoate molecules obtained excellent-to-good inhibitory against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes with IC50 values ranging between 77.18 ± 8.62 to 461.35 ± 28.54 µM for AChE and 23.86 ± 4.07 to 306.62 ± 32.46 µM for BuChE. The calculations revealed the probable interactions and their characteristics at an atomic level. Indeed, the docking scores of DES, flavokawain C, pregnanolone, and methyl 3,4,5-trihydroxybenzoate for AChE are -6.685, -6.247, -6.672, and -5.183 (kcal/mol), respectively. This value for the compounds against BuChE is -6.042, -8.851, -5.655, and -5.898 (kcal/mol), respectively. Additionally, these compounds significantly decreased ovarian cancer cell viability. Additionally, 100 µM dose of all molecules caused good reductions in ovarian cancer cell viability.

Cadmium Chloride Induces Memory Deficits and Hippocampal Damage by Activating the JNK/p66Shc/NADPH Oxidase Axis.

This study investigated whether the mechanism underlying the neurotoxic effects of cadmium chloride (CdCl2) in rats involves p66Shc. This study comprised an initial in vivo experiment followed by an in vitro experiment. For the in vivo experiment, male rats were orally administered saline (vehicle) or CdCl2 (0.05 mg/kg) for 30 days. Thereafter, spatial and retention memory of rats were tested and their hippocampi were used for biochemical and molecular analyses. For the in vitro experiment, control or p66Shc-deficient hippocampal cells were treated with CdCl2 (25 µM) in the presence or absence of SP600125, a c-Jun N-terminal kinase (JNK) inhibitor. Cadmium chloride impaired the spatial learning and retention memory of rats; depleted levels of glutathione and manganese superoxide dismutase; increased reactive oxygen species (ROS), tumor necrosis factor α, and interleukin 6; and induced nuclear factor kappa B activation. Cadmium chloride also decreased the number of pyramidal cells in the CA1 region and induced severe damage to the mitochondria and endoplasmic reticulum of cells in the hippocampi of rats. Moreover, CdCl2 increased the total unphosphorylated p66Shc, phosphorylated (Ser36) p66Shc, phosphorylated JNK, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, cytochrome c, and cleaved caspase-3. A dose-response increase in cell death, ROS, DNA damage, p66Shc, and NADPH oxidase was also observed in cultured hippocampal cells treated with CdCl2. Of note, all of these biochemical changes were attenuated by silencing p66Shc or inhibiting JNK with SP600125. In conclusion, CdCl2 induces hippocampal ROS generation and apoptosis by promoting the JNK-mediated activation of p66Shc.

Relationship between musculoskeletal disorders, job demands, and burnout among emergency nurses.

Musculoskeletal disorders (MSDs) represent one of the most common occupational problems in nursing. MSDs can negatively impact one's quality of life. The aim of the study was to investigate the relationship between MSDs, job demands, and burnout among emergency nurses. The researchers hypothesized that increased job demands were associated with more MSDs and consequently higher levels of burnout. The study was conducted on a convenience sample of 58 nurses working in the emergency departments of Zagazig University Hospital and Al-Ahrar, Hospital Egypt from October to December 2010, using a cross-sectional analytic design. Data were collected using a self-administered questionnaire that included the Standardized Nordic Questionnaire, the Job Content Questionnaire, and the Maslach Burnout Inventory. The results revealed that 32.8% of the nurses were overweight and 17.2% were obese. The most common sites of pain were the neck (67.2%), shoulder (65.5%), and lower back (63.8%). Lower back pain was the most common site affected (72.4%) with a mean 5.1 on a scale ranging from 0 to 13. A positive correlation existed between the scores of job demand and burnout (r = 0.340, p < 0.01), and the number of reported MSDs with the score of job demand (r = 0.33, p < 0.05). Multiple linear stepwise regression analysis identified the score of job demand and the severity of lower back pain as positive independent predictors of the burnout whereas the job demand score was the independent predictor of the number of MSDs. This study documents an increased prevalence of MSDs among emergency nurses, as predicted by increased job demand and associated with a higher level of burnout. Hence, it is important for hospital and nursing administrators to address the factors contributing to job stress and burnout, with emphasis on job satisfaction and work organization to alleviate the burden of psychosocial factors in this setting.