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.

The spread of drug-resistant forms of TB dictates the need for surgical treatment in the complex of anti-tuberculosis measures in Russia. Most often, surgical intervention is performed in the case of pulmonary tuberculoma or fibrotic cavitary tuberculosis (FCT). This study is devoted to the search for biomarkers that characterize the course of disease in surgical TB patients. It is assumed that such biomarkers will help the surgeon decide on the timing of the planned operation. A number of serum microRNAs, potential regulators of inflammation and fibrosis in TB, selected on the basis of PCR-Array analysis, were considered as biomarkers. Quantitative real time polymerase chain reaction and receiver operating curves (ROC) were used to verify Array data and to estimate the ability of microRNAs (miRNAs) to discriminate between healthy controls, tuberculoma patients, and FCT patients. The study showed that miR-155, miR-191 and miR-223 were differentially expressed in serum of tuberculoma with “decay” and tuberculoma without “decay” patients. Another combination (miR-26a, miR-191, miR-222 and miR-320) forms a set to differentiate between tuberculoma with “decay” and FCT. Patients with tuberculoma without “decay” diagnosis differ from those with FCT in serum expression of miR-26a, miR-155, miR-191, miR-222 and miR-223. Further investigations are required to evaluate these sets on a larger population so as to set cut-off values that could be applied in laboratory diagnosis.

Tuberculosis (TB) remains a leading cause of infectious disease mortality worldwide, despite the COVID-19 pandemic. The mechanisms by which SARS-CoV-2 affects tuberculosis progression have not yet been established. Here, we compared the level of inflammation in the wall of the tuberculoma and in the parenchymal lung tissue of 30 patients diagnosed with tuberculoma without a history of COVID-19 and 30 patients diagnosed with tuberculoma 3 months after COVID-19. We also characterized TB activity in these patients using a panel of TB-associated miRNAs. Histopathological changes were examined in the resection material, and the expression level of cytokine/chemokine genes was determined by qRT-PCR. In patients with a history of COVID-19, the histological data obtained suggested activation of tuberculosis. In the same group of patients, as opposed to those without a history of COVID-19, equally high levels of pro-inflammatory cytokines/chemokines were expressed both in the tuberculoma wall and in the periphery of the resected specimen. A full set of miRNAs (miR-191, miR-193a, miR-222, miR-223, miR-155, miR-26a, and miR-150) were downregulated in the sera of patients with TB and active COVID-19 co-infection compared to controls. Our observations indicate signs of tuberculosis activation resulting from COVID-19 infection.

Accurate normalization of qRT-PCR data in pulmonary tuberculosis (TB) research requires reference genes whose expression is invariant across clinically relevant matrices, yet no studies have addressed this in lesion tissue and blood concurrently. We assessed the expression stability of eight popular housekeeping genes—ACTB, B2M, GAPDH, HPRT1, PPIA, RPL13A, UBC and YWHAZ—in lung tuberculomas and peripheral blood mononuclear cells (PBMCs) from TB patients. Standardized extraction and amplification yielded Cq values that were ranked by geNorm, NormFinder, BestKeeper and comparative Delta CT, with consensus scores generated in RefFinder; and correlation analysis was conducted in order to select the most suitable genes to work collectively for future normalization. The consensus analysis placed PPIA, YWHAZ and HPRT1 at the top, while GAPDH and UBC were the least stable. Our findings endorse a three-gene panel (PPIA, YWHAZ, HPRT1) for robust normalization of host gene-expression studies in both lesion tissue and PBMCs in pulmonary TB and highlight the necessity of context-specific reference-gene validation.

Objective: to analyze the results of a morphological study of the lung tissue and small airways in the surgical material of patients with a combination of tuberculoma and nontuberculous mycobacteriosis of the lungs caused by different types of pathogen.Materials and methods. A comparative retrospective histological study of the surgical material of 34 patients with a combination of LT and NM with established microbiological different types of non-tuberculous mycobacteria (NTMB) and 36 patients with LT without concomitant pathology was carried out.Results. Diagnostically significant differences in the morphological picture of TL and NM, which manifests its morphological features in areas free from foci of tuberculosis, were revealed. The features of changes in the lung tissue and small airways in patients with slow- and fast-growing types of NTMB are shown.Conclusion. The results obtained are aimed at resolving the issue of possible correction of chemotherapy in the postoperative period.

An observation from practice is given – surgical treatment of a patient with advanced tuberculosis of a single lung and a pronounced lung displacement. Patient A., 47 years old, after 3 months from the left pneumonectomy for fibrocavernous tuberculosis complained of dyspnea at rest, and dysphagia, underwent CT scan, which showed a pronounced displace ment of a single right lung with tuberculoma to the left. At the first stage of the surgery, the overstretched section of a single lung with tuberculoma was resected, the displaced lung was put back and a hernial orifice was strengthened with a mesh implant. At the second stage, the extrapleural thoracoplasty was made with resection of I–IV ribs from the side of pneumonectomy to reduce the volume of the left hemithorax and prevent relapse of mediastinal hernia. As a result, the patient stopped dyspnea and dysphagia, radiographically a single right lung was visualized in the right hemithorax.