High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity.

P-glycoprotein (encoded by the ABCB1 gene) has a dual role in regulating inflammation and reducing chemotherapy efficacy in various diseases, but there are few studies focused on pulmonary TB patients. In this study, our objective was to identify a list of genes that correlate with high and low levels of ABCB1 gene expression in the lungs of pulmonary TB patients with different activity of chronic granulomatous inflammation. We compared gene expression in two groups of samples (with moderate and high activity of tuberculomas) to identify their characteristic gene signatures. Gene expression levels were determined using quantitative PCR in samples of perifocal area of granulomas, which were obtained from 65 patients after surgical intervention. Subsequently, two distinct gene signatures associated with high inflammation activity were identified. The first signature demonstrated increased expression of HIF1a, TGM2, IL6, SOCS3, and STAT3, which correlated with high ABCB1 expression. The second signature was characterized by high expression of TNFa and CD163 and low expression of ABCB1. These results provide insight into various inflammatory mechanisms and association with P-gp gene expression in lung tissue of pulmonary TB patients and will be useful in the development of a host-directed therapy approach to improving the effectiveness of anti-TB treatment.

Wall Thickness of Industrial Multi-Walled Carbon Nanotubes Is Not a Crucial Factor for Their Degradation by Sodium Hypochlorite.

The propensity of multi-walled carbon nanotubes (MWCNTs) for biodegradation is important for their safe use in medical and technological applications. Here, we compared the oxidative degradation of two samples of industrial-grade MWCNTs-we called them MWCNT-d and MWCNT-t-upon their treatment with sodium hypochlorite (NaOCl). The MWCNTs had a similar inner diameter but they differed about 2-fold in the outer diameter. Electron microscopy combined with morphometric analysis revealed the different degradation of the two types of MWCNTs after their incubation with NaOCl-the thicker MWCNT-d were damaged more significantly than the thinner MWCNT-t. The both types of MWCNTs degraded at the inner side, but only MWCNT-d lost a significant number of the outer graphitic layers. Raman spectroscopy demonstrated that both MWCNTs had a similar high defectiveness. Using energy-dispersive X-ray spectroscopy, we have shown that the more degradable MWCNT-d contained the same level of oxygen as MWCNT-t, but more metal impurities. The obtained results suggest that the biodegradability of MWCNTs depends not only on the wall thickness but also on the defects and impurities. Thus, the biodegradability can be regulated by the synthesis conditions or the post-synthesis modifications. Such degradation flexibility may be important for both medical and industrial applications.