Size-resolved particle oxidative potential in the office, laboratory, and home: Evidence for the importance of water-soluble transition metals.

Particulate matter (PM) oxidative potential (OP) is an emerging health metric, but studies examining the OP of indoor PM are rare. This paper focuses on the relationships between respiratory exposure to OP and PM water-soluble composition in indoor environments. Size-resolved PM samples were collected between November 2015 and June 2016 from an office, home (including bedroom, living room, and storeroom), and laboratory using a MOUDI sampler. Particles from each source were segregated into eleven size bins, and the water-soluble metal content and dithiothreitol (DTT) loss rate were measured in each PM extract. The water-soluble OP (OPws) of indoor PM was highest in the office and lowest in the home, varying by factors of up to 1.2; these variations were attributed to differences in occupation density, occupant activity, and ventilation. In addition, the particulate Cu, Mn, and Fe concentrations were closely correlated with OPws in indoor particles; the transition metals may have acted as catalysts during oxidation processes, inducing ·OH formation through the concomitant consumption of DTT. The OPws particle size distributions featured single modes with peaks between 0.18 and 3.2 µm across all indoor sites, reflecting the dominant contribution of PM3.2 to total PM levels and the enhanced oxidative activity of the PM3.2 compared to PM>3.2. Lung-deposition model calculations indicated that PM3.2 dominated the pulmonary deposition of the OPws (>75%) due to both the high levels of metals content and the high deposition efficiency in the alveolar region. Therefore, because OPws has been directly linked to various health effects, special attention should be given to PM3.2.

RasGRF2 promotes migration and invasion of colorectal cancer cells by modulating expression of MMP9 through Src/Akt/NF-κB pathway.

Ras-specific guanine nucleotide-releasing factor 2 (RasGRF2) is a member of the guanine nucleotide exchange factors family which is expressed in a variety of tissues and cancer. However, the role of RasGRF2 in cancer is less reported, especially in colorectal cancer(CRC). Hence, the present study aimed to investigated the function of RasGRF2 and ways in which it affects tumor progression in CRC samples and cell lines. We first measured RasGRF2 mRNA level in 26 paired tumor and nontumor colon tissues after colon cancer surgical resection, and determined RasGRF2 protein level in 97 paired paraffin-embedded colon cancer tissues, and found that levels of RasGRF2 mRNA and protein were increased in colorectal tumor tissues, compared with adjacent non-tumor tissues. We then examined the effects of RasGRF2 knockdown on proliferation, migration and invasion were analyzed in CRC cells (SW480, HCT116 and LS174T). HCT116 cells with RasGRF2 knockdown were injected into the tail vein in nude mice to yield metastatic model, and tumor metastasis was measured as well. We found that knockdown of RasGRF2 in CRC cells reduced their migration and invasion in vitro and metastasis in mice. Furthermore, we explored the underlying molecular mechanism for RasGRF2-mediated CRC migration and invasion. The results showed that knockdown of RasGRF2 in CRC cells impairing the expression of MMP9 and inhibiting the activation of Src/Akt and NF-κB signaling. We conclude that RasGRF2 plays a role in controlling migration and invasion of CRC and modulates the expression of MMP9 through Src/PI 3-kinase and the NF-κB pathways.

Epigenetic hypomethylation and upregulation of GD3s in triple negative breast cancer.

BACKGROUND: Breast cancer remains a major health problem in the world. Triple-negative breast cancer (TNBC) is an aggressive subtype with very poor prognosis. Up to now, the mechanism behind TNBC's activity is still unclear and no candidate drug target has been identified. Thus, it is of critical importance to elucidate the pathways in TNBC and identify the relevant biomarkers. Recent studies showed that ganglioside D3 synthase (GD3s) played a very important role in development of cancers. However, the physiological functions and associated pathways of GD3s in TNBC are still unclear. METHODS: In silico analysis of the expression of GD3s in TNBC was conducted using The Cancer Genome Atlas (TCGA) and Oncomine databases. The proliferation of breast cancer cells was measured by MTT assay, colony formation by the soft agar method, and migration and invasion using Boyden chamber inserts. The methylation level of the gene encoding GD3s, ST8SIA1, in specimens was assessed by qMS-PCR and in silico using the UCSC gene browser. Protein expression was examined via immunohistochemistry (IHC), qRT-PCR and Western immunoblotting. RESULTS: In silico analysis showed a higher GD3s expression in ER- than ER+ breast cancers and GD3s was also highly expressed in TNBC compared to other types of breast cancers. The elevated GD3s expression in TNBC cells and tissues was associated with hypomethylation of the ST8SIA1 gene. Overexpression of GD3s in human breast cancer cells increased their proliferation, migration, invasion and colony formation ability. GD3s expression in breast cancers was closely associated with relapse-free survival (RFS) and overall survival (OS). CONCLUSIONS: In summary, these results suggest that GD3s may be a potential biomarker and drug target in treatment of TNBC.