Serological microRNAs as biomarkers for the diagnosis of adolescent tuberculosis infection in pleura
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE179816 | GEO | 2023/07/31
REPOSITORIES: GEO
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Project description:<p>Pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are common chronic diseases that threaten human health. Patients with DM are susceptible to PTB, an important factor that aggravates the complications of diabetes. However, the molecular regulatory mechanism underlying the susceptibility of patients with DM to PTB infection remains unknown. Healthy subjects, patients with primary PTB and patients with primary PTB complicated by DM were recruited according to inclusion and exclusion criteria. Peripheral whole blood was collected, and alteration profiles and potential molecular mechanisms were further analyzed using integrated bioinformatics analysis of metabolomics and transcriptomics. In this study, transcriptional data revealed that lipocalin 2 (LCN2), defensin alpha 1 (DEFA1), peptidoglycan recognition protein 1 (PGLYRP1) and integrin subunit alpha 2b (ITGA2B) were significantly upregulated, while chloride intracellular channel 3 (CLIC3) significantly down-regulated in PTB-DM by contrast to HC group. Additionally, the IL-17, PI3K-AKT and PPAR signaling pathways are important for PTB infection and regulation of PTB-complicated diabetes. Metabolomic data showed that glycerophospholipid metabolism, carbon metabolism and fat digestion and absorption processes were enriched in the differential metabolic analysis. Finally, integrated analysis of both metabolomic and transcriptomic data indicated that the NOTCH1/JAK/STAT signaling pathway is important in PTB complicated by DM. In conclusion, PTB infection altered the transcriptional and metabolic profiles of patients with DM. Metabolomic and transcriptomic changes were highly correlated in PTB-infected patients with DM. Peripheral metabolite levels may be used as biomarkers for PTB management in patients with DM.</p><p><strong>IMPORTANCE:</strong> The comorbidity of diabetes mellitus (DM) significantly increases the risk of tuberculosis infection and adverse tuberculosis treatment outcomes. Most previous studies have focused on the relationship between the effect of blood glucose control and the outcome of anti-tuberculosis treatment in pulmonary tuberculosis (PTB)-DM; however, early prediction and the underlying molecular mechanism of susceptibility to PTB infection in patients with DM remain unclear. Here, transcriptome sequencing and untargeted metabolomics were performed to elucidatethe key molecules and signaling pathways involved in PTB infection and the susceptibility of patients with diabetes to PTB. Our findings contribute to the development of vital diagnostic biomarkers for PTB or PTB-DM and provide acomprehensive understanding of molecular regulation during disease progression.</p>
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Project description:The aim of this study was to compare the transcriptional response to TB in regions of different incidence / prevalence. Experimental Design: Whole blood collected in tempus tubes from patients with different spectra of TB disease. All patients were sampled prior to the initiation of any antimycobacterial therapy. Active Pulmonary TB: PTB - All patients confirmed by isolation of Mycobacterium Tuberculosis on culture of sputum. Latent TB: LTB - All patients were screened at a tuberculosis clinic. All were positive by Interferon-Gamma Release assay(IGRA); specifically Quantiferon Gold In-Tube Assay (Cellestis, Australia). Latent patients had no clinical, or microbiological evidence of active infection and were asymptomatic. Experimental Variables: Patient group: Active PTB; Latent TB. There are no healthy controls in this dataset as it was being used for validation only. Controls: Latent TB individuals are used as a control for PTB in this dataset since there are few to no unexposed adult controls in Cape Town.
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2024-04-14 | GSE172150 | GEO
Project description:Differences in the activity of monocytes/macrophages, important target cells of Mycobacterium tuberculosis, might influence tuberculosis progression. With the purpose of identifying candidate genes for tuberculosis susceptibility we infected with M. tuberculosis monocytes from both, healthy elders (a tuberculosis susceptibility group) and elderly tuberculosis patients, and performed a microarray experiment. We detected 78 differentially expressed transcripts and confirmed these results by quantitative PCR of selected genes. We found that monocytes from tuberculosis patients showed similar expression patterns of these genes regardless of whether they were obtained from younger or elder patients. Only one of the detected genes corresponded to a cytokine: IL-26, a member of the IL-10 cytokine family that we found downregulated in infected monocytes from tuberculosis patients. We have analyzed total RNA from Mycobacterium tuberculosis infected monocytes. We have isolated CD14+ cells (monocytes) from peripheral blood mononuclear cells by magnetic separation, and infected them for 4 days with 1 bacterium per monocyte. Blood donors were 7 elderly patients with pulmonary tuberculosis (average age: 83 years; sex: 3 men and 4 women) and 8 non-tuberculous volunteers (81 years, 6 men and 2 women).
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Project description:<p><strong>BACKGROUND:</strong> Pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are prevalent chronic diseases with substantial implications for human health. DM patients are more susceptible to PTB, which exacerbates diabetes-related complications. However, the complex molecular mechanisms underlying the enhanced susceptibility of DM patients to PTB infection remain poorly understood. </p><p><strong>RESULTS:</strong> α-and β-diversity of gut microbiota were significantly reduced in PTB patients and PTB-DM patients. In addition, the abundances of families <em>Lachnospiraceae</em> and <em>Ruminococcaceae</em> in <em>Firmicutes</em> phylum were downregulated in PTB patients and further diminished in PTB-DM patients. On the other hand, untargeted metabolomics in frozen serum and stool samples indicated that such as Phenylalanine, tyrosine and tryptophan biosynthesis, Arginine and proline metabolism, Tryptophan metabolism and Histidine metabolism et al were consistently and significantly altered in PTB patients and PTB-DM patients, with the significant upregulation of most metabolites. Amino acids like serine, proline, histidine et al were both remarkably elevated in PTB and PTB-DM patients. The correlation network analysis reveals the relationships between the shared microbial biomarkers and the shared metabolic pathways. </p><p><strong>CONCLUSIONS:</strong> This research contributes to the exploration of pivotal diagnostic biomarkers for both patients with PTB and PTB accompanied by diabetes. Specifically, shared reductions were identified in the genera <em>g-Roseburia</em>, <em>g-Ruminococcaceae_UCG.013</em>, <em>g-Ruminococcaceae_NK4A214</em>, <em>g-Lachnospiraceae_unclassified</em> and <em>g-Firmicutes_unclassified</em>, in addition to notable regulation of amino acids like glycine, serine and histine in patients with PTB and PTB-DM. Our study expands the comprehension of the intricate connections linking gut microbiota, fecal metabolites and serum metabolites in PTB and PTB-DM patients.</p>
2023-12-15 | MTBLS8729 | MetaboLights