Pharmacological Mechanisms of Kirenol against Ovarian Carcinoma: A Network Pharmacology and Experimental Validation Study In Vitro.

BACKGROUND: Ovarian carcinoma is an aggressive gynecological malignancy. Kirenol, a diterpene compound, has recently gained attention for its potential anticancer properties. However, its exact anti-tumor mechanism remains largely unexplored. OBJECTIVE: In this study, we explored the inhibitory effects of Kirenol on ovarian cancer using network pharmacology and in vitro experiments and elucidated its underlying mechanisms. METHODS: Through the utilization of molecular docking, we established a network of proteinprotein interactions (PPI), which unveiled CDK4 as an essential target. Additionally, gene enrichment and pathway analysis highlighted the significance of the PI3K/AKT pathway. The viability of ovarian cancer cells and normal ovarian epithelial cells was evaluated using CCK8 assays to determine the effect of Kirenol. Following in vitro tests, cell colony formation, wound healing, flow cytometry, and Western blotting were conducted to assess its impact on cell proliferation, metastasis, apoptosis, and the cell cycle. RESULTS: Kirenol significantly reduced the viability of ovarian cancer cells (SKOV3 and A2780) compared to normal ovarian epithelial cells (IOSE-80). Moreover, Kirenol efficiently suppressed the growth and movement, caused a cell cycle halt, and stimulated programmed cell death in SKOV3 and A2780 cells. Through molecular analysis, it was observed that Kirenol increased the expression of Bax while decreasing the expression of MMP2, MMP9, and Bcl-2. It also attenuated the phosphorylation of PI3K, AKT, and RB and downregulated CDK4 and CCND1 expression. Notably, co-treatment with the PI3K pathway inhibitor LY294002 enhanced the inhibitory effect of Kirenol on ovarian cancer cells. CONCLUSION: In summary, the combined results of our network pharmacology analysis and in vitro tests emphasized that Kirenol hinders the growth of ovarian cancer cells, causes cell cycle arrest, enhances apoptosis, and hampers migration, possibly by regulating the PI3K/AKT/CDK4 signaling pathway.

How perceived school culture relates to work engagement among primary and secondary school teachers? Roles of affective empathy and job tenure.

Evidence suggests that perceived school culture is the most powerful predictor of teachers' work performance. However, studies to date have paid little attention to the potential mechanisms behind this association. On the basis of the job demands-resources (JD-R) model, the present study explored the mediating role of affective empathy and the moderating role of job tenure in the association between perceived school culture and teachers' work engagement. 647 primary and secondary school teachers completed questionnaires measuring perceived school culture, affective empathy, and work engagement. After gender and educational level were included as covariates, the results showed that perceived school culture positively correlated with teachers' work engagement, and more importantly, this association was partially mediated by affective empathy. In addition, job tenure significantly moderated the direct association between perceived school culture and work engagement. Specifically, there was a stronger association between perceived school culture and work engagement for teachers with shorter job tenure than those with longer job tenure. The findings suggested the direct effect of perceived school culture on work engagement, and the indirect effect of perceived school culture on work engagement through the mediating role of affective empathy. These findings enrich our understanding of how perceived school culture associates with work engagement, and highlight the moderating role of job tenure in the direct association between perceived school culture and work engagement.

Effect of skill proficiency on motor imagery ability between amateur dancers and non-dancers.

Evidence has shown that athletes with high motor skill proficiency possess higher motor imagery ability than those with low motor skill proficiency. However, less is known whether this superiority in motor imagery ability emerges over amateur athletes. To address the issue, the present study aimed to investigate the individual differences in motor imagery ability between amateur dancers and non-dancers. Forty participants completed a novel dance movement reproduction task and measures of the vividness of visual imagery questionnaire (VVIQ) and the vividness of motor imagery questionnaire (VMIQ). The results showed that, relative to non-dancers, amateur dancers had higher ability of motor imagery to reproduce the lower-limb and upper-limb dance movements during the dance movement reproduction task. Besides, amateur dancers displayed higher abilities of the visual motor imagery and the kinesthetic imagery, but comparable visual imagery ability as the non-dancers. These findings suggest that the mental representation of motors but not the visual is affected by the motor skill levels, due to the motor imagery practice in sports amateurs.

Stressful Life Events and Subjective Well-Being in Vocational School Female Adolescents: The Mediating Role of Depression and the Moderating Role of Perceived Social Support.

Stressful life events and subjective well-being are negatively related, but there is little research in the current literature exploring the mediating and moderating mechanisms underlying this association, especially for female adolescents in vocational schools who are subjected to undesirable life events. In the present study, we examined the mediating role of depression in the association between stressful life events and female adolescents' subjective well-being, as well as the moderating role of perceived social support in the direct and indirect relations involved. The participants were 1,096 vocational school female adolescents, who completed the questionnaires regarding stressful life events, subjective well-being, depression, and perceived social support. The results showed that depression partially mediated the relation between stressful life events and subjective well-being. Importantly, perceived social support moderated the direct link between stressful life events and subjective well-being, and the indirect link between stressful life events and depression, but not the indirect link between depression and subjective well-being. Especially, female adolescents high in perceived social support displayed higher levels of subjective well-being and lower levels of depression in facing with stressful life events than those low in perceived social support. These findings highlight the mechanisms underlying the relationship between stressful life events and subjective well-being in vocational school female adolescents.

Decreased Filamin b expression regulates trophoblastic cells invasion through ERK/MMP-9 pathway in pre-eclampsia.

OBJECTIVES: The purpose of this study was to investigate the expression of Filamin b in the placental placenta of patients with early or late onset pre-eclampsia (PE) and its potential effects on the pathophysiology of the disease. METHODS AND METHODS: Immunohistochemistry staining, western blot assays and real time PCR were used to detect the expression level of FLN-b. The expression levels of MMP-2, MMP-9 and ERK1/2 proteins from control and FLN-b-silenced JEG-3 cells were also detected by western blot and JEG-3 cell invasion. RESULTS: Compared with normal term pregnancies placentas, the FLN-b expression was significantly lower than that of women with PE, its level in late-onset PE is lower than in early-onset PE. In FLN-b-silenced JEG-3 cells, the protein levels of MMP-2, MMP-9 and phosphorylated ERK1/2 decreased markedly and the number of cells penetrating through the transwell chamber membrane is also greatly reduced. CONCLUSIONS: Down-regulation of FLN-b inhibits the ERK/MMP-2 and MMP-9 pathways, leading to trophoblastic invasion disorders in the PE placenta.

Sensitivity analysis of ozone formation and transport for a central California air pollution episode.

We developed a first- and second-order sensitivity analysis approach with the decoupled direct method to examine spatial and temporal variations of ozone-limiting reagents and the importance of local vs upwind emission sources in the San Joaquin Valley of central California for a 5 day ozone episode (Jul 29th to Aug 3rd, 2000). Despite considerable spatial variations, nitrogen oxides (NO(x)) emission reductions are overall more effective than volatile organic compound (VOC) control for attaining the 8 h ozone standard in this region for this episode, in contrast to the VOC control that works better for attaining the prior 1 h ozone standard. Interbasin source contributions of NO(x) emissions are limited to the northern part of the SJV, while anthropogenic VOC (AVOC) emissions, especially those emitted at night, influence ozone formation in the SJV further downwind. Among model input parameters studied here, uncertainties in emissions of NO(x) and AVOC, and the rate coefficient of the OH + NO2 termination reaction, have the greatest effect on first-order ozone responses to changes in NO(x) emissions. Uncertainties in biogenic VOC emissions only have a modest effect because they are generally not collocated with anthropogenic sources in this region.

Wintertime indoor air levels of PM10, PM2.5 and PM1 at public places and their contributions to TSP.

From 26 October 2002 to 8 March 2003, particulate matter (PM) concentrations (total suspended particles [TSP], PM10, PM2.5 and PM1) were measured at 49 public places representing different environments in the urban area of Beijing. The objectives of this study were (1) to characterize the indoor PM concentrations in public places, (2) to evaluate the potential indoor sources and (3) to investigate the contribution of PM10 to TSP and the contributions of PM2.5 and PM1 to PM10. Additionally, The indoor and outdoor particle concentrations in the same type of indoor environment were employed to investigate the I/O level, and comparison was made between I/O levels in different types of indoor environment. Construction activities and traffic condition were the major outdoor sources to influence the indoor particle levels. The contribution of PM10 to TSP was even up to 68.8%, while the contributions of PM2.5 and PM1 to PM10 were not as much as that of PM10 to TSP.