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Fig 1.

Cell viablity of BEAS-2B cells in the presence of SiNPs.

(A) Cell viability of 3.125, 5, 6.25, 12.5, 25, 50, 100μg/mL SiNPs-treated groups for 24 h exposure. (B) Cell viability following 5 μg/mL SiNPs after the5th, 10th, 20th, 30th passage. Data are expressed as means ± S.D. *p<0.05 compared with control group.

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Fig 1 Expand

Fig 2.

Apoptosis of BEAS-2B cells after exposure to SiNPs at the 5th, 10th, 20th, 30th passage.

(A) Apoptotic populations of cells double-stained with PI- and FITC-labled Annexin V using flow cytometry. (B) SiNPs increased the apoptosis rate in a passage-dependent manner. Data are expressed as means ± S.D. *p<0.05compared with control group.

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Fig 2 Expand

Fig 3.

Effect of SiNPs on the expression of caspase-9 and caspase-3 in BEAS-2B cells.

(A) Protein levels induced by SiNPs at the 5th, 10th, 20th, 30th passage. (B) Relative densitometric analysis. Data are expressed as means ± S.D. *p<0.05 compared with control group.

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Fig 3 Expand

Fig 4.

Analysis of gene DNA methylation status between the SiNPs-treated BEAS-2B cells (g2) and control cells (g1) using Infinium HumanMethylation450 BeadChip.

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Fig 4 Expand

Fig 5.

DNA methylation of CREB3L1 and Bcl-2 promoters in the 30th passage of BEAS-2B cells exposed to SiNPsin the presence of the methyltransferase inhibitor 5-aza.

Data are expressed as means ± S.D. *p<0.05 compared with control group. #p<0.05 compared with the 30th passage SiNPs-treated group.

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Fig 5 Expand

Fig 6.

mRNA expression of CREB3L1 and Bcl-2 in the 30th passage of BEAS-2B cells exposed to SiNPs and the methyltransferase inhibitor 5-aza.

Data are expressed as means ± S.D. *p<0.05 compared with control group. #p<0.05 compared with the 30th passage of the SiNP-treated group.

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Fig 6 Expand

Fig 7.

Effect of SiNPs on the PI3K/Akt/CREB/Bcl-2 signaling pathway.

(A)Protein expression of p-Akt, Akt, CREB, Bcl-2. (B) Relative densitometric analysis. Data are expressed as means ±S.D.*p<0.05 compared with control group.

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Fig 7 Expand

Fig 8.

Schematic representation of the DNA hypermethylation of CREB3L1 and Bcl-2, associated with mitochondrial-mediated apoptosis via PI3K/Akt signaling pathway induced by low-dose SiNPs.

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Fig 8 Expand