Translational research : the journal of laboratory and clinical medicine
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EsxA is an essential virulence factor for Mycobacterium tuberculosis (Mtb) pathogenesis as well as an important biomarker for Mtb detection. In this study, we use light microscopy and deep learning-based image analysis to classify the morphologic changes of macrophages infected by Mycobacterium marinum (Mm), a surrogate model for Mtb. Macrophages were infected either with the mCherry-expressing Mm wild type strain (Mm(WT)), or a mutant strain with deletion of the esxA-esxB operon (Mm(ΔEsxA:B)). ⋯ Deconvolutional analysis successfully reconstructed the morphologic features used by CNN for classification, which are indistinguishable to naked eyes and distinct from intracellular mycobacteria. This study presents a deep learning-aided imaging analytical tool that can accurately detect virulent mycobacteria-infected macrophages by cellular morphologic changes. The observed morphologic changes induced by EsxA warrant further studies to fill the gap from molecular actions of bacterial virulence factors to cellular morphology.
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There is a growing need for a more accurate, real-time assessment of tumor status and the probability of metastasis, relapse, or response to treatment. Conventional means of assessment include imaging and tissue biopsies that can be highly invasive, may not provide complete information of the disease's heterogeneity, and not ideal for repeat analysis. Therefore, a less-invasive means of acquiring similar information at greater time points is necessary. ⋯ These potential biomarkers can be captured in a liquid biopsy and analyzed to determine disease status. To achieve these goals, numerous technologies have been developed. In this review, we discuss both prominent and newly developed technologies for circulating tumor cell capture and analysis and their clinical impact.
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The role of adhesion G protein-coupled receptors (aGPCRs) in cancer has become increasingly evident in recent years. Yet, data supporting the contribution of this family of genes to hematological malignancies, particularly acute myeloid leukemia (AML) are limited. Here, we use publicly available genomic data to characterize the expression of the 33 aGPCRs in patients with AML and examine whether upregulation of these genes is associated with the clinical and molecular characteristics of patients. ⋯ Via Ingenuity Pathway Analysis, we identified the interleukin-8 signaling pathway among the most activated pathways in patients with high aGPCRs expression. Overall, our data suggest that particular aGPCRs are frequently upregulated in AML and associated with poor clinical outcome. Future functional and mechanistic analyses are needed to address the role of aGPCRs in AML.
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Prostate cancer (PCa) is one of the most common cancers types among men. Development and progression of PCa is associated with aberrant expression of oncogenic splicing-variants (eg, AR-v7), suggesting that dysregulation of the splicing process might represent a potential actionable target for PCa. Expression levels (mRNA and protein) of SF3B1, one of the main components of the splicing machinery, were analyzed in different cohorts of PCa patients (clinically localized [n = 84], highly aggressive PCa [n = 42], and TCGA dataset [n = 497]). ⋯ Moreover, inhibition of SF3B1 activity by pladienolide-B reduced functional parameters of aggressiveness (proliferation/migration/tumorspheres-formation/apoptosis) in PCa cell lines, irrespective of AR-v7 expression, and reduced viability of primary PCa cells. Antitumor actions of pladienolide-B involved: (1) inhibition of PI3K/AKT and JNK signaling pathways, (2) modulation of tumor markers and splicing variants (AR-v7/In1-ghrelin), and (3) regulation of key components of mRNA homeostasis-associated machineries (spliceosome/SURF/EJC). Altogether, our results demonstrated that SF3B1 is overexpressed and associated with malignant features in PCa, and its inhibition reduces PCa aggressiveness, suggesting that SF3B1 could represent a novel prognostic biomarker and a therapeutic target in PCa.
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The aim of this study was to explore the relationship between serum soluble angiotensin converting enzyme 2 (sACE2), parameters of cardiopulmonary exercise testing and plasma asymmetric dimethylarginine (ADMA), a marker of oxidative stress-induced endothelial dysfunction. This has not been previously evaluated. We assessed 50 consecutive ambulatory patients with chronic systolic heart failure and left ventricular ejection fraction (LVEF) ≤45%. ⋯ Meanwhile, we observed a negative correlation between ADMA and pVO2 (r = -0.424, P = 0.00227) and positive correlations between ADMA and VE/VCO2 slope (r = 0.515, P < 0.001), ΔDBP (r = 0.391, P = 0.00568), mitral E/Ea ratio (r = 0.426, P = 0.00219). In multivariate logistic regression analysis, sACE2 was independently associated with peak oxygen uptake (% predicted) after adjusting for body mass index (BMI) and mitral E/Ea ratio (odds ratio [OR] 0.81 (0.58-0.94), P = 0.041) and associated with oxygen pulse (VO2/HR) (%) after adjusting for age, gender, BMI and mitral E/Ea ratio (OR 0.83 [0.68-0.95], P = 0.025). Therefore in stable chronic systolic heart failure patients, higher sACE2 activity is independently associated with diminished exercise capacity and correlates with elevated systemic oxidative stress-mediated endothelial dysfunction.