Translational research : the journal of laboratory and clinical medicine
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Pancreatic cancer is an aggressive malignancy that carries a high mortality rate. A major contributor to the poor outcome is the lack of effective molecular markers. The purpose of this study was to develop protein markers for improved prognostication and noninvasive diagnosis. ⋯ Combining AGP1 with CA 19-9 enhanced the diagnostic performance, with an AUC of 0.963. This study suggests that AGP1 is a novel prognostic biomarker in pancreatic cancer tissue. Serum AGP1 levels may be useful as part of a biomarker panel for early detection of pancreatic cancer but further studies are needed.
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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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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.