Prostate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and ...accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcriptional repressor with an important role in human malignancies, including leukemia, colorectal carcinoma, and lung cancer, but its role in prostate and breast cancer is unknown. We have found that Gfi1 epigenetic silencing is a common event in prostate and breast cancer. Gfi1 re-expression in prostate and breast cancer cell lines displaying Gfi1 epigenetic silencing decreases cell proliferation, reduced colony formation density, and tumor growth in nude mice xenografts. In addition, we found that Gfi1 repress alpha 1-anti-trypsin (AAT) and alpha 1-anti-chymotrypsin (ACT) expression, two genes with important functions in cancer development, suggesting that Gfi1 silencing promotes tumor growth by increasing AAT and ACT expression in our system. Finally, Gfi1 epigenetic silencing could be a promising biomarker for prostate cancer progression because it is associated with shorter disease-free survival. In conclusion, our findings strongly indicate that Gfi1 epigenetic silencing in prostate and breast cancer could be a crucial step in the development of these two-well characterized endocrine related tumors.
Attempts to discover genes that are involved in the pathogenesis of major psychiatric disorders have been frustrating and often fruitless. Concern is building about the need to understand the complex ...ways in which nature and nurture interact to produce mental illness. We analyze the epigenome in several brain regions from schizophrenic patients with severe cognitive impairment using high-resolution (450K) DNA methylation array. We identified 139 differentially methylated CpG sites included in known and novel candidate genes sequences as well as in and intergenic sequences which functions remain unknown. We found that altered DNA methylation is not restricted to a particular region, but includes others such as CpG shelves and gene bodies, indicating the presence of different DNA methylation signatures depending on the brain area analyzed. Our findings suggest that epimutations are not relatables between different tissues or even between tissues' regions, highlighting the need to adequately study brain samples to obtain reliable data concerning the epigenetics of schizophrenia.
Purpose Detection of DNA hypermethylation has emerged as a novel molecular biomarker for prostate cancer diagnosis and evaluation of prognosis. We sought to define whether a hypermethylation profile ...of patients with prostate cancer on androgen deprivation would predict castrate resistant prostate cancer. Materials and Methods Genome-wide methylation analysis was performed using a methylation cancer panel in 10 normal prostates and 45 tumor samples from patients placed on androgen deprivation who were followed until castrate resistant disease developed. Castrate resistant disease was defined according to EAU (European Association of Urology) guideline criteria. Two pathologists reviewed the Gleason score, Ki-67 index and neuroendocrine differentiation. Hierarchical clustering analysis was performed and relationships with outcome were investigated by Cox regression and log rank analysis. Results We found 61 genes that were significantly hypermethylated in greater than 20% of tumors analyzed. Three clusters of patients were characterized by a DNA methylation profile, including 1 at risk for earlier castrate resistant disease (log rank p = 0.019) and specific mortality (log rank p = 0.002). Hypermethylation of ETV1 (HR 3.75) and ZNF215 (HR 2.89) predicted disease progression despite androgen deprivation. Hypermethylation of IRAK3 (HR 13.72), ZNF215 (HR 4.81) and SEPT9 (HR 7.64) were independent markers of prognosis. Prostate specific antigen greater than 25 ng/ml, Gleason pattern 5, Ki-67 index greater than 12% and metastasis at diagnosis also predicted a negative response to androgen deprivation. Study limitations included the retrospective design and limited number of cases. Conclusions Epigenetic silencing of the mentioned genes could be novel molecular markers for the prognosis of advanced prostate cancer. It might predict castrate resistance during hormone deprivation and, thus, disease specific mortality. Gene hypermethylation is associated with disease progression in patients who receive hormone therapy. It could serve as a marker of the treatment response.
Gliomas are the most common type of primary brain tumor. Although tremendous progress has been achieved in the recent years in the diagnosis and treatment, its molecular etiology remains unknown. In ...this regard, epigenetics represents a new approach to study the mechanisms that control gene expression and function without changing the sequence of the genome. In the present paper we describe the main findings about the alterations of cell signaling pathways in the most aggressive glioma in the adult population, namely, glioblastoma, in which epigenetic mechanisms and the emerging role of cancer stem cell play a crucial function in the development of new biomarkers for its detection and prognosis and the corresponding development of new pharmacological strategies.
Attempts to discover genes that are involved in the pathogenesis of major psychiatric disorders have been frustrating and often fruitless. Concern is building about the need to understand the complex ...ways in which nature and nurture interact to produce mental illness. We analyze the epigenome in several brain regions from schizophrenic patients with severe cognitive impairment using high-resolution (450K) DNA methylation array. We identified 139 differentially methylated CpG sites included in known and novel candidate genes sequences as well as in and intergenic sequences which functions remain unknown. We found that altered DNA methylation is not restricted to a particular region, but includes others such as CpG shelves and gene bodies, indicating the presence of different DNA methylation signatures depending on the brain area analyzed. Our findings suggest that epimutations are not relatables between different tissues or even between tissues' regions, highlighting the need to adequately study brain samples to obtain reliable data concerning the epigenetics of schizophrenia.
Background
The global COVID-19 pandemic has challenged nurse leaders in ways that one could not imagine. Along with ongoing priorities of providing high quality, cost-effective and safe care, nurse ...leaders are also committed to promote an ethical climate that support nurses’ moral courage for sustaining excellence in patient and family care.
Aim
This study is directed to develop a structure equation model of crisis, ethical leadership and nurses’ moral courage: mediating effect of ethical climate during COVID-19.
Ethical consideration
Approval was obtained from Ethics Committee at Faculty of Nursing, Alexandria University, Egypt.
Methods
A cross-sectional design was used to conduct this study using validated scales to measure the study variables. It was conducted in all units of two isolated hospitals in Damanhur, Egypt. A convenient sample of 235 nurses was recruited to be involved in this study.
Results
This study revealed that nurses perceived a moderate mean percent (55.49 ± 3.46) of overall crisis leadership, high mean percent (74.69 ± 6.15) of overall ethical leadership, high mean percent (72.09 ± 7.73) of their moral courage, and moderate mean percent of overall ethical climate (65.67 ± 12.04). Additionally, this study declared a strong positive statistical significant correlation between all study variables and indicated that the independent variable (crisis and ethical leadership) can predict a 0.96, 0.6, respectively, increasing in the dependent variable (nurses’ moral courage) through the mediating impact of ethical climate.
Conclusion
Nursing administrators should be conscious of the importance of crisis, ethical leadership competencies and the role of ethical climate to enhance nurses’ moral courage especially during pandemic. Therefore, these findings have significant contributions that support healthcare organizations to develop strategies that provide a supportive ethical climate. Develop ethical and crisis leadership competencies in order to improve nurses' moral courage by holding meetings, workshops, and allowing open dialogue with nurses to assess their moral courage.
Healthcare organizations with practitioners who exhibit proactive work behavior and career adaptability acquire a competitive advantage in the face of many adversities. Entrepreneurial leadership ...(EL) is a new leadership approach that has a huge impact on followers' behavior, although research into its theory and empirical evidence is still in its infancy.
A non-probability convenience sample methodology (n = 450) was utilized to choose study participants, who were equally dispersed among the two private hospitals in Alexandria. A cross-sectional study was carried out in all departments of the hospitals, which were chosen at random using a simple random procedure. Three validated scales were used in this study to measure the study variables and establish a structural equation model.
The result of this study revealed that nurses perceived moderate mean scores of all variables; entrepreneurial leadership (140.84 ± 11.94), proactive work behavior (46.02 ± 5.85), and career adaptability (85.55 ± 10.35). In addition, the structured equation model revealed a goodness fit index and presents that entrepreneurial leadership significantly affects nurses' proactive work behavior with an estimated β of 0.555, coefficient of regression C.R. of 4.006, at P value < 0.001. Also, it significantly affects career adaptability with an estimated β of .834, a coefficient of regression C.R. of 3.491 at P value < 0.001.
The developed structural equation model confirmed the significant impact of entrepreneurial leadership (EL) on nurses' proactive work behavior (PWB) and career adaptability (CA)". Therefore, this study offers important implications for nurse managers, staff nurses, hospital human resources management practice, and academics.
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