12-O-deacetyl-phomoxanthone A inhibits ovarian tumor growth and metastasis by downregulating PDK4.

AIMS: The xanthone dimer 12-O-deacetyl-phomoxanthone A (12-ODPXA) was extracted from the secondary metabolites of the endophytic fungus Diaporthe goulteri. The 12-ODPXA compound exhibited anticancer properties in murine lymphoma; however, the anti-ovarian cancer (OC) mechanism has not yet been explored. Therefore, the present study evaluated whether 12-ODPXA reduces OC cell proliferation, metastasis, and invasion by downregulating pyruvate dehydrogenase kinase (PDK)4 expression. METHODS: Cell counting kit-8, colony formation, flow cytometry, wound healing, and transwell assays were performed to examine the effects of 12-ODPXA on OC cell proliferation, apoptosis, migration, and invasion. Transcriptome analysis was used to predict the changes in gene expression. Protein expression was determined using western blotting. Glucose, lactate, and adenosine triphosphate (ATP) test kits were used to measure glucose consumption and lactate and ATP production, respectively. Zebrafish xenograft models were constructed to elucidate the anti-OC effects of 12-ODPXA. RESULTS: The 12-ODPXA compound inhibited OC cell proliferation, migration, invasion, and glycolysis while inducing cell apoptosis via downregulation of PDK4. In vivo experiments showed that 12-ODPXA suppressed tumor growth and migration in zebrafish. CONCLUSION: Our data demonstrate that 12-ODPXA inhibits ovarian tumor growth and metastasis by downregulating PDK4, revealing the underlying mechanisms of action of 12-ODPXA in OC.

Social isolation and well-being in veterans with mental illness.

BACKGROUND: Veterans with mental illness are a growing population in the United States (US). For some veterans, their military service has a negative effect on well-being. Social isolation is problematic for veterans' mental health by increasing incidence of depression, suicidal ideation or attempts, and readmittance to psychiatric hospitals. Social support is a protective factor for individuals with mental illness and is key to a successful military-to-civilian transition. AIM: Thus, we examine the relationship of social isolation on well-being among veterans with any mental illness. METHODS: This cross-sectional correlational study consisted of a sample of 146 US veterans with any mental illness. A three-step hierarchical regression analysis was used to determine if social isolation is a predictor of well-being after controlling for demographics, functional limitations and depression. RESULTS: Findings revealed social isolation was positively correlated with functional limitations (r = 0.48, p < 0.001), depression (r = 0.66, p < 0.001) and negatively correlated with well-being (r = -.64, p < 0.001). Hierarchical regression analysis revealed social isolation was negatively correlated (ß = -.44, p < 0.001) with well-being. Overall, our three-step model accounted a total of 50% of variance in well-being, a large effect size. CONCLUSION: The findings underscore the importance of assessing the relationship of social isolation on well-being in veterans with mental illness. The findings also highlight promising targets to improve prevention and psychosocial interventions to improve well-being among veterans with mental illness.

Abnormal expression and clinical value analysis of long noncoding RNA cancer susceptibility candidate 2 in children with severe pneumonia complicated with respiratory failure.

OBJECTIVE: Severe pneumonia occurs commonly in children and is the main cause of clinical infant mortality. This study tested the expression pattern of long noncoding RNA cancer susceptibility candidate 2 (CASC2) in the serum of children with severe pneumonia and explored its clinical values. METHODS: Serum levels of CASC2 were detected in 145 children with severe pneumonia. All cases were divided into two groups based on their respiratory failure (RF) condition. Receiver operating characteristic (ROC) and Kaplan-Meier (K-M) curves were plotted for the diagnostic and prognostic ability evaluation. Multivariate cox regression analysis was done for the examination of independent influence factors. RESULTS: The serum levels of CASC2 significantly decreased in children with severe pneumonia in contrast with healthy individuals and reached the lowest value in those with RF. Serum CASC2 can distinguish severe pneumonia and predicted the development of RF. Based on the 28-day survival data, cases with low CASC2 levels had a poor survival rate. CASC2 (hazard ratio [HR] = 0.068, 95% confidence interval [CI] = 0.016-0.292, P < 0.001) and age (HR = 2.806, 95% CI = 1.240-6.394, P < 0.001) were independent influence factor for the poor prognosis of children with severe pneumonia. CONCLUSION: Downregulation of serum CASC2 was related to the occurrence of RF in children with severe pneumonia and may be a predictor of the poor prognosis. This study will provide a potential biomarker for severe pneumonia treatment in clinic.

[Mechanism of polyphyllin â targeting EGFR to affect proliferation and apoptosis of human breast cancer cells].

This study aims to investigate the molecular mechanism of polyphyllin Ⅰ(PPⅠ) inhibiting proliferation of human breast cancer cells. Human breast cancer BT474 and MDA-MB-436 cells were treated with different concentrations of PPⅠ, and then the effect of PPⅠ on cell proliferation was detected by MTT assay, trypan blue dye exclusion assay, real-time cell analysis, and clone forming assay, respectively. The apoptosis was detected by Annexin V-FITC/PI staining and then analyzed by flow cytometry. The change of mitochondrial membrane potential was detected by flow cytometry after fluorescent probe JC-1 staining. Western blot was used to detect protein expression and phosphorylation. Molecular docking was performed to detect the binding between PPⅠ and EGFR. The affinity between PPⅠ and EGFR was determined by drug affinity responsive target stability assay. The results indicated that PPⅠ inhibited the proliferation and colony formation of BT474 and MDA-MB-436 cells in a time-and concentration-dependent manner. The PPⅠ treatment group showed significantly increased apoptosis rate and significantly decreased mitochondrial membrane potential. PPⅠ down-regulated the expression of pro-caspase-3 protein, promoted the cleavage of PARP, and significantly reduced the phosphorylation levels of EGFR, Akt, and ERK. Molecular docking showed that PPⅠ bound to the extracellular domain of EGFR and formed hydrogen bond with Gln366 residue. Drug affinity responsive target stability assay confirmed that PPⅠ significantly prevented pronase from hydrolyzing EGFR, indicating that PPⅠ and EGFR have a direct binding effect. In conclusion, PPⅠ inhibited the proliferation and induced apoptosis of breast cancer cells by targeting EGFR to block its downstream signaling pathway. This study lays a foundation for the further development of PPⅠ-targeted drugs against breast cancer.

An Exploration of Spiritual Well-being Among Homeless People: A Hierarchical Regression Analysis.

This study explored homeless people's (N = 164) spiritual well-being (SWB) in relation to race, mental illness, physical disease, resilience, and trait mindfulness. The results of hierarchical regression analysis revealed that variables of race (p = 0.003), mental illness (p = 0.04), resilience (p < 0.001) and trait mindfulness (p < 0.001) contributed to participants' SWB. These findings were critical to research related to homelessness and service provisions in finding that homeless people with certain backgrounds (e.g., mental illness) might have lower SWB than their counterparts. This research also revealed protective factors (e.g., resilience) that could help promote SWB.

Paris saponin VII, a direct activator of AMPK, induces autophagy and exhibits therapeutic potential in non-small-cell lung cancer.

Paris saponin VII (PSVII), a bioactive constituent extracted from Trillium tschonoskii Maxim., is cytotoxic to several cancer types. This study was designed to explore whether PSVII prevents non-small-cell lung cancer (NSCLC) proliferation and to investigate its molecular target. AMP-activated protein kinase (AMPK) has been implicated in the activation of autophagy in distinct tissues. In cultured human NSCLC cell lines, PSVII induces autophagy by activating AMPK and inhibiting mTOR signaling. Furthermore, PSVII-induced autophagy activation was reversed by the AMPK inhibitor compound C. Computational docking analysis showed that PSVII directly interacted with the allosteric drug and metabolite site of AMPK to stabilize its activation. Microscale thermophoresis assay and drug affinity responsive target stability assay further confirmed the high affinity between PSVII and AMPK. In summary, PSVII acts as a direct AMPK activator to induce cell autophagy, which inhibits the growth of NSCLC cells. In the future, PSVII therapy should be applied to treat patients with NSCLC.

Nursing students' trait mindfulness and psychological stress: A correlation and mediation analysis.

BACKGROUND: Nursing students face a great amount of psychological stress during their nursing education. Mindfulness-based training has received increased recognition from nurse educators regarding its effect on reducing students' psychological stress. Study evidence has supported that cultivation of trait mindfulness through Mindfulness-based training was the key to this effect. However, there is a lack of research that focuses on intricate relationships between various facets of trait mindfulness and psychological stress. OBJECTIVE: Examining the relationships between various trait mindfulness facets and psychological stress. DESIGN: A cross-sectional design was used to collect data on trait mindfulness facets and psychological stress. PARTICIPANTS: A convenience sample of 99 undergraduate nursing students from a Bachelor of Nursing program completed this study. SETTING: This study was conducted in a university in the south-eastern United States. METHOD: Participants completed an online questionnaire, which collected their demographic information, trait mindfulness (the Five Factor Mindfulness Questionnaire), and psychological stress (the Perceived Stress Scale-10). Correlation and mediation analyses were applied. RESULTS: Other than the trait mindfulness facet of observing, the remaining three facets (acting with awareness, non-judging, and non-reactivity) were negatively correlated with psychological stress. Observing had little to low correlations with non-judging and acting with awareness, but attained a moderately positive correlation with non-reactivity. Moreover, observing could indirectly predict psychological stress, when non-reactivity served as a mediator. Finally, non-judging partially mediated the relationship between acting with awareness and psychological stress. CONCLUSIONS: The results of the current study can help nurse educators better understand the intricate relationships between various facets of trait mindfulness and psychological stress. Specifically, facets of acting with awareness, non-judging, and non-reactivity are directly relevant to the reduction of psychological stress. Therefore, regardless of formal or informal practices of mindfulness, nurse educators ought to assist students in cultivating these facets as means toward stress management.

Understanding self-report Multidimensional Attitudes Scale Toward People with Disabilities: An exploratory analysis.

PURPOSE/OBJECTIVE: This study aimed to explore the factor structure of the Multidimensional Attitudes Scale Toward People With Disabilities (MAS) using participants from South Korea and assess the impact of participants' social desirability on this South Korean version of the MAS (MAS-K). Research Method/Design: One hundred eighty-nine college students without disabilities from 4 universities in South Korea completed an online survey. Among them, 75 were females. Participants completed the MAS-K and a social desirability scale. We used principal axis factoring with promax rotation to examine the factor structure of the MAS-K, and correlations between factors and social desirability measure. RESULTS: We obtained a 27-item 4-factor MAS-K. Four factors were negative affect (α = .89), ease-unease (α = .75), positive cognition (α = .86), and avoidant behavior (α = .88). The interfactor correlations ranged from .18 to .61. The correlations between the social desirability measure and the 4 factors in the MAS-K ranged from -.23 to -.33. CONCLUSIONS/IMPLICATIONS: The MAS-K retrieved from this study may help researchers identify unique attitudinal factors that need to be addressed to promote social inclusion of PWD in South Korea. Moreover, the emergence of the MAS-K highlights the necessity to develop culturally relevant versions of the MAS. This line of research will facilitate researchers' worldwide investigations regarding attitudes toward PWD and discussions about the rights of PWD. Finally, this study also pointed out the potential impact of social desirability on attitude measurement using the MAS. (PsycINFO Database Record