Translational research : the journal of laboratory and clinical medicine
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Cardiovascular risk (CVR) tends to be estimated in the short-term, which underestimates lifetime (LT)-CVR of young subjects. We determined whether LT-CVR is associated with a multimarker score of oxidative status in young adults and whether this association is independent of traditional CVR factors. Seventy-two young adults were stratified into: (1) low or (2) high LT-CVR, and (3) stable coronary artery disease (SCAD). ⋯ OxyScore and AntioxyScore were significantly higher in subjects with high LT-CVR than with low LT-CVR or with SCAD. OxyScore, but not AntioxyScore, was associated with LT-CVR independently of each traditional CVR factor. This study for the first time demonstrates a positive association between oxidative stress and the risk of first and recurrent CV events in young adults.
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Chemokine-like factor 1 (CKLF1) is a potential target for ischemic stroke therapy. The NOD-like receptor protein 3 (NLRP3) inflammasome has been postulated to mediate inflammatory responses during ischemic/reperfusion (I/R) injury. The compound IMM-H004 is a novel coumarin derivative that can improve cerebral I/R injury. ⋯ IMM-H004 downregulated the amount of CKLF1 binding with C-C chemokine receptor type 4, further suppressing the activation of NLRP3 inflammasome and the following inflammatory response, ultimately protecting the ischemic brain. This preclinical study established the efficacy of IMM-H004 as a potential therapeutic medicine for permanent cerebral ischemia. These results support further efforts to develop IMM-H004 for human clinical trials in acute cerebral ischemia, particularly for patients who are not suitable for reperfusion therapy.
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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.