Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes

A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential

Cyanidin-3-Glucoside, A Natural Product Derived From Blackberry, Exhibits Chemopreventive And Chemotherapeutic Activity

Epidemiological data suggest that consumption of fruits and vegetables has been associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study. In cultured JB6 cells, C3G was able to scavenge ultraviolet B-induced *OH and O2-* radicals. In vivo studies indicated that C3G treatment decreased the number of non-malignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. Pretreatment of JB6 cells with C3G inhibited UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and tumor necrosis factor-alpha. These inhibitory effects appear to be mediated through the inhibition of MAPK activity. C3G also blocked TPA-induced neoplastic transformation in JB6 cells. In addition, C3G inhibited proliferation of a human lung carcinoma cell line, A549. Animal studies showed that C3G reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice. Mechanistic studies indicated that C3G inhibited migration and invasion of A549 tumor cells. These finding demonstrate for the first time that a purified compound of anthocyanin inhibits tumor promoter-induced carcinogenesis and tumor metastasis in vivo

MicroRNA-646 inhibits the proliferation of ovarian granulosa cells via insulin-like growth factor 1 (IGF-1) in polycystic ovarian syndrome (PCOS)

Introduction: Polycystic ovarian syndrome (PCOS) is a common endocrinopathy in women. MicroRNAs (miRNAs) have been proven to play a crucial role in balancing the proliferation and apoptosis of granulosa cells (GCs) in PCOS. Material and methods: The miRNA of PCOS was screened by bioinformatics analysis, and microRNA 646 (miR-646) was found to be involved in insulin-related pathways by enrichment analysis. The cell counting kit-8 (CCK-8), cell colony formation, and the 5-ethynyl-2’-deoxyuridine (EdU) assays were used to explore the effect of miR-646 on proliferation of GCs, flow cytometry was used to measure the cell cycle and apoptosis, and Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to explore the biological mechanism of miR-646. The human ovarian granulosa cells KGN were selected by measuring the miR-646 and via insulin-like growth factor 1 (IGF-1) levels and used for cell transfection. Results: Overexpressed miR-646 inhibited KGN cell proliferation, and silenced miR-646 advanced it. Most cells were arrested in the S phase of cell cycle with overexpressed-miR-646, while after silencing miR-646, cells were arrested in the G2/M phase. And the miR-646 mimic raised apoptosis in KGN cells. Also, a dual-luciferase reporter proved the regulation effect of miR-646 on IGF-1, miR-646 mimic inhibited IGF-1, and miR-646 inhibitor advanced IGF-1. The cyclin D1, cyclin-dependent kinase 2 (CDK2), and B-cell CLL/lymphoma 2 (Bcl-2) levels were inhibited with overexpressed-miR-646, while silenced-miR-646 promoted their expression, and the bcl-2-like protein 4 (Bax) level was the opposite. This study found that silenced-IGF1 antagonized the promotive effect of the miR-646 inhibitor on cell proliferation. Conclusions: MiR-646 inhibitor treatment can promote the proliferation of GCs by regulating the cell cycle and inhibiting apoptosis, while silenced-IGF-1 antagonizes it

Moderating Effect of Mindfulness on the Relationships Between Perceived Stress and Mental Health Outcomes Among Chinese Intensive Care Nurses

This study aimed to explore the potential moderating effect of mindfulness and its facets on the relationships among perceived stress and mental health outcomes (burnout, depression, anxiety, and subjective well-being) among Chinese intensive care nurses. A total of 500 Chinese intensive care nurses completed self-report measures of mindfulness, burnout syndromes, perceived stress, depression, anxiety, and subjective well-being. Correlation and hierarchical multiple regressions were applied for data analysis. Mindfulness moderated the effects of perceived stress on emotional exhaustion (the core component of burnout syndrome), depression, anxiety, positive affect, and negative affect but not on the other two dimensions of burnout and life satisfaction. Further analyses indicated that the ability to act with awareness was particularly crucial in improving the effects of perceived stress on depression. These results further broaden our understanding of the relationships between perceived stress and burnout, depression, anxiety, and subjective well-being by demonstrating that mindfulness may serve as a protective factor that alleviates or eliminates the negative effects of perceived stress on depression, anxiety, burnout syndrome, and subjective well-being and may instigate further research into targeted mindfulness interventions for Chinese intensive care nurses

Filamin A phosphorylation by Akt promotes cell migration in response to arsenic

We had previously reported that trivalent arsenic (As3+), a well-known environmental carcinogen, induces phosphorylation of several putative Akt substrates. In the present report, we characterized one of these substrates by immunoprecipitation and proteomics analysis. The results indicate that a cytoskeleton remodeling protein, filamin A, with a molecular weight around 280 kDa, is phosphorylated by Akt in HEK-293 cells treated with As3+, which was also confirmed in human bronchial epithelial cell line, BEAS-2B cells. Additional biochemical and biological studies revealed that serine 2152 (S2152) of filamin A is phosphorylated by activated Akt in the cells treated with As3+. To further confirm the importance of Akt-dependent filamin A S2152 phosphorylation in As3+-induced cell migration, we over-expressed either wild type filamin A or the mutated filamin A in which the S2152 was substituted with alanine (S2152A). The capability of cell migration was reduced significantly in the cells expressing the mutated filamin A (S2152A). Clinically, we found that increased expression of filamin A predicts poorer overall survival of the lung cancer patients with adenocarcinoma. Thus, these data suggest that Akt dependent filamin A phosphorylation is one of the key events in mediating As3+-induced carcinogenesis. Antagonizing Akt signaling can ameliorate As3+-induced filamin A phosphorylation and cell migration, which may serve as a molecular targeting strategy for malignancies associated with environmental As3+ exposure

Levels of emotional exhaustion and its relationship with depression and posttraumatic stress disorder in ICU nurses: the moderating effect of mindfulness

Objective To investigate the level of emotional exhaustion and its relationship with depression and posttraumatic stress disorder symptoms in intensive care unit (ICU) nurses and explore the moderating effects of mindfulness. Methods From March, 2016 to April 2017, we conducted a survey of the levels of emotional exhaustion, mindfulness, depression and posttraumatic stress disorder among 500 Chinese ICU nurses in 11 provinces and cities using the Dimension of Emotional Exhaustion in Maslach Burnout Inventory-Human Service Survey (MBI-HSS), Five Facet Mindfulness Questionnaire-Chinese Version (FFMQ-CH), Center for Epidemiological Studies Depression Scale (CES-D) and Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C). Results The mean score of emotional exhaustion was 20.82±9.79 among the ICU nurses participated in this survey. The level of emotional exhaustion differed significantly between male and female nurses (F=1.4, P < 0.05) and among those with different ICU working experiences (F=3.85, P < 0.05). Emotional exhaustion was negatively correlated with mindfulness (r=-0.80, P < 0.01) and positively correlated with depression (r=0.61, P < 0.01) and posttraumatic stress disorder (r=0.42, P < 0.01). Mindfulness moderated the relationship of emotional exhaustion with depression and posttraumatic stress disorder symptoms. Conclusion The level of emotional exhaustion is closely correlated with mindfulness, depression and posttraumatic stress disorder symptoms in ICU nurses. An increased mindfulness level can help the nurses reduce depression and posttraumatic stress disorder symptoms to promote their psychological wellbeing

Paradoxical roles of mineral dust induced gene on cell proliferation and migration/invasion.

Increased expression of mineral dust-induced gene (mdig, also named as mina53, MINA, or NO52) has been observed in a number of human cancers. The mechanism of how mdig contribute to the pathogenesis of cancer remains to be fully elucidated. In this report, we demonstrated that overexpression of mdig decreased the nuclear staining signal by 4',6-diamidino-2-phenylindole (DAPI), along with a considerable enhancement in cell proliferation. Silencing mdig by shRNA resulted in a statistically significant decrease of cell proliferation. Intriguingly, mdig overexpression reduced the capacity of the cells in migration and invasion in vitro, whereas silencing mdig by shRNA/siRNA enhanced migration and invasion. Clinically, we found that increased expression of mdig in cancer tissues correlates with poorer overall survival of the lung cancer patients, esp., for those without lymph node metastasis. Taken together, our results suggest that mdig plays opposite roles on cell growth and motility, which possibly indicates the paradoxical effect of mdig at the different stages of carcinogenesis