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Fig 1.

Histology of lungs of Non-Diabetic vs Diabetic after seven days of ECIG, HTP and CS exposure.

Non-Diabetic lungs + ECIG showing limited lung injury with thin interstitial alveolar wall and fine capillary vessels (Fig 1A; magnification x 20). Rare inflammatory cells in the wall and intra-alveolar spaces are noted (Fig 1B; magnification x 40). Sections from Diabetic + ECIG lungs demonstrate limited areas of thickening of the interstitial wall, capillary congestion and limited areas of inflammation (Fig 1C; magnification x 20). Arrows point to a significant presence of inflammatory cells (Fig 1D; magnification x 40). Non-Diabetic lungs + HTP showing patches of alveolar wall edema and capillary congestion (Fig 1E; magnification x 20). Those findings were significantly worse in Diabetic lungs exposed to HTP (Fig 1F; magnification x 20). Arrows point to presence of inflammatory cells (Fig 1H; magnification x 40). Non-diabetic lungs showing significant lung injury with thick interstitial alveolar walls and capillary congestion (Fig 1J; magnification X20). inflammatory cells in the wall and intra-alveolar spaces are noted (Fig 1K; magnification x40). Sections from Diabetic lungs demonstrate worsening lung injury when compared to non-diabetic animals with destruction of the alveolar architecture and edematous distension of the alveolar sacs (Fig 1L; magnification x 20). Worsening recruitment of inflammatory cells is now observed as well (Fig 1M; magnification x 40). Non-Diab + HTP lungs revealed patches of alveolar wall edema and capillary congestion (Fig 1E and 1F). These findings were significantly worse in Diab + HTP when compared to Non-Diab +HTP. Non-Diab + CS and Diab + CS lungs demonstrated significant acute lung injury in both groups. Diab + CS lung injury was significantly worse when compared to Non-Diab + CS with worsening edematous and thickened alveolar walls, in addition to significant infiltration by inflammatory cells (Fig 1k and 1L).

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Fig 1 Expand

Fig 2.

Mean wet to dry ratio (W/D) (A)and albumin level in the BALF (B) of Control, ECIG and CS for Non-Diabetic and Diabetic mice.

Error bars represent SE. Asterisks indicate statistically significant associations (*P-value: < 0.05, **P-value: < 0.005, **** P-value: < 0.0001).

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Fig 2 Expand

Fig 3.

Transcriptional expression of TNF-α (A) IL-1β (B) and IL-6 (C) of Control, ECIG and CS for Non-Diabetic and Diabetic mice.

Expression of inflammatory mediators was assessed by real-time PCR. Error bars represent SE and sterisks indicate statistically significant associations (* = P-value: < 0.05, ** = P-value: < 0.005, *** = P-value: < 0.0005, **** = P-value: < 0.0001).

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Fig 3 Expand

Fig 4.

ROS detection in lung tissues.

Five μm thickness slides of lung sections for Control, ECIG and CS from Non-Diabetic and diabetic mice were incubated with Dihydroethidium (DHE), and fluorescent images of ethidium-stained tissue were analyzed. ROS levels were significantly higher in ECIG and CS and exposed diabetic mice when compared to ECIG and CS Non-Diabetic mice exposure respectively.

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Fig 4 Expand

Fig 5.

Cell death assessment.

Terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) and Hoechst staining of lung sections for Control, ECIG and CS from Non-Diabetic and diabetic mice. Significant increase in apoptotic activity was noted in ECIG and CS and exposed diabetic mice when compared to ECIG and CS Non-Diabetic mice respectively.

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Fig 5 Expand