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The family Bignoniaceae includes Handroanthus impetiginosus trees, which are sparsely distributed in the northeast of Brazil. Natural products play a vital role in the discovery of drugs for various diseases. Many plants have been used as sources of medicines because of their chemical diversity and potent bioactivity. Handroanthus impetiginosus has been used traditionally to cure a wide range of illnesses, such as cancer, oxidative stress, and inflammation. This work highlights the cytotoxicity, cell death, and routes of apoptosis in lung cancer cells (A549) and the anti-inflammatory and antioxidant effects of roasted Handroanthus impetiginosus (lapacho/taheebo) in normal cells. The cell viability assay indicated that puffing roasted taheebo is nontoxic to a normal cell line up to 500 µg/mL but significantly toxic to A549 cells. The roasted lapacho/taheebo also increases reactive oxygen species (ROS) generation in A549 lung cancer cells, and cellular apoptosis via a mitochondrial intrinsic pathway was confirmed. The roasted lapacho/taheebo significantly inhibited both colony formation and cell migration ability, highlighting its potential as an anticancer agent. Additionally, this study demonstrates that roasted taheebo enhanced the expression of genes for BAX accumulation and decreased Bcl-2 gene expression through the p53 signaling pathway. Furthermore, research on the anti-inflammatory properties of roasted taheebo revealed a strong NO inhibition as well as the inhibition of inflammatory mediators (TNF-α, iNOS, COX-2, IL-6, and IL-8) through the NF-κB signaling pathway. However, in H2O2-induced HaCaT cells, roasted taheebo extract significantly reduced oxidative stress by upregulating the level of expression of antioxidative markers (SOD, CAT, GPx, and GST) at 50 μg/mL. As a result, roasted taheebo justifies investigation in animal and clinical trials as a possible source of antioxidants, anti-inflammatory substances, and anti-cancer compounds.

Rationale: Contacts of patients with tuberculosis (TB) constitute an important target population for preventive measures because they are at high risk of infection with Mycobacterium tuberculosis and progression to disease.Objectives: We investigated biosignatures with predictive ability for incident TB.Methods: In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, PCR, and the pair ratio algorithm in a training/test set approach. Overall, 79 progressors who developed TB between 3 and 24 months after diagnosis of index case and 328 matched nonprogressors who remained healthy during 24 months of follow-up were investigated.Measurements and Main Results: A four-transcript signature derived from samples in a South African and Gambian training set predicted progression up to two years before onset of disease in blinded test set samples from South Africa, the Gambia, and Ethiopia with little population-associated variability, and it was also validated in an external cohort of South African adolescents with latent M. tuberculosis infection. By contrast, published diagnostic or prognostic TB signatures were predicted in samples from some but not all three countries, indicating site-specific variability. Post hoc meta-analysis identified a single gene pair, C1QC/TRAV27 (complement C1q C-chain / T-cell receptor-α variable gene 27) that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events.Conclusions: Collectively, we developed a simple whole blood-based PCR test to predict TB in recently exposed household contacts from diverse African populations. This test has potential for implementation in national TB contact investigation programs.

Background: People with diabetes are more likely to develop tuberculosis (TB) and to have poor TB‐treatment outcomes than those without. We previously showed that blood transcriptomes in people with TB‐diabetes (TB‐DM) co‐morbidity have excessive inflammatory and reduced interferon responses at diagnosis. It is unknown whether this persists through treatment and contributes to the adverse outcomes. Methods: Pulmonary TB patients recruited in South Africa, Indonesia and Romania were classified as having TB‐DM, TB with prediabetes, TB‐related hyperglycaemia or TB‐only, based on glycated haemoglobin concentration at TB diagnosis and after 6 months of TB treatment. Gene expression in blood at diagnosis and intervals throughout treatment was measured by unbiased RNA‐Seq and targeted Multiplex Ligation‐dependent Probe Amplification. Transcriptomic data were analysed by longitudinal mixed‐model regression to identify whether genes were differentially expressed between clinical groups through time. Predictive models of TB‐treatment response across groups were developed and cross‐tested. Results: Gene expression differed between TB and TB‐DM patients at diagnosis and was modulated by TB treatment in all clinical groups but to different extents, such that differences remained in TB‐DM relative to TB‐only throughout. Expression of some genes increased through TB treatment, whereas others decreased: some were persistently more highly expressed in TB‐DM and others in TB‐only patients. Genes involved in innate immune responses, anti‐microbial immunity and inflammation were significantly upregulated in people with TB‐DM throughout treatment. The overall pattern of change was similar across clinical groups irrespective of diabetes status, permitting models predictive of TB treatment to be developed. Conclusions: Exacerbated transcriptome changes in TB‐DM take longer to resolve during TB treatment, meaning they remain different from those in uncomplicated TB after treatment completion. This may indicate a prolonged inflammatory response in TB‐DM, requiring prolonged treatment or host‐directed therapy for complete cure. Development of transcriptome‐based biomarker signatures of TB‐treatment response should include people with diabetes for use across populations. [ABSTRACT FROM AUTHOR]