The American journal of pathology
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Tendon stromal cells isolated from patients with chronic shoulder rotator cuff tendon tears have dysregulated resolution responses. Current therapies do not address the biological processes concerned with persistent tendon inflammation; therefore, new therapeutic approaches that target tendon stromal cells are required. We examined whether two specialized proresolving mediators (SPMs), lipoxin B4 (LXB4) and resolvin E1 (RvE1), modulate the bioactive lipid mediator profiles of IL-1β-stimulated tendon cells derived from patients with shoulder tendon tears and healthy volunteers. ⋯ RvE1 treatment up-regulated the proresolving receptor human resolvin E1 compared with vehicle-treated cells. Incubation in LXB4 or RvE1 moderated the proinflammatory phenotype of patient-derived tendon tear cells, regulating markers of tendon inflammation, including podoplanin, CD90, phosphorylated signal transducer and activator of transcription 1, and IL-6. LXB4 and RvE1 counterregulate inflammatory processes in tendon stromal cells, supporting the role of these molecules as potential therapeutics to resolve tendon inflammation.
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With the rapid development of image scanning techniques and visualization software, whole slide imaging (WSI) is becoming a routine diagnostic method. Accelerating clinical diagnosis from pathology images and automating image analysis efficiently and accurately remain significant challenges. Recently, deep learning algorithms have shown great promise in pathology image analysis, such as in tumor region identification, metastasis detection, and patient prognosis. ⋯ In this review, the pathology image segmentation process using deep learning algorithms is described in detail. The goals are to provide quick guidance for implementing deep learning into pathology image analysis and to provide some potential ways of further improving segmentation performance. Although there have been previous reviews on using machine learning methods in digital pathology image analysis, this is the first in-depth review of the applications of deep learning algorithms for segmentation in WSI analysis.
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Neutrophil elastase (NE) is necessary for effective sterilization of phagocytosed bacterial and fungal pathogens; however, NE increases alveolocapillary permeability and induces proinflammatory cytokine production in sepsis-induced acute respiratory distress syndrome. Under septic conditions, the pulmonary endothelial glycocalyx covering on the healthy endothelium surface is injured, but the contribution of NE to this injury remains unknown. Our aim was to examine whether NE-induced pulmonary endothelial injury is associated with endotoxemia. ⋯ Ultrastructural analysis revealed attenuated vascular endothelial injury and clear preservation of the endothelial glycocalyx in G-CSFKO mice. Moreover, after LPS exposure, survival rate was approximately ninefold higher among sivelestat-injected mice than control mice, and sivelestat treatment potently preserved vascular endothelial structures and the endothelial glycocalyx. In conclusion, NE is associated with pulmonary endothelial injury under LPS-induced endotoxemic conditions.
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Review
Understanding the Similarities and Differences between Hepatic and Pulmonary Veno-Occlusive Disease.
Hepatic veno-occlusive disease (HVOD), alias sinusoidal obstruction syndrome, may develop as a complication of chemotherapy in the setting of hematopoietic stem cell transplantation. HVOD is less frequently described after exposure to chemotherapy in the nontransplant setting and can also be a complication after ingestion of toxins, such as pyrrolizidine alkaloids. Veno-occlusive disease may also affect the lungs, and it is therefore termed pulmonary veno-occlusive disease (PVOD). ⋯ Both HVOD and PVOD share common histopathological features and pathophysiologic mechanisms. Both clinical disorders are rare complications that can appear after exposure to the common inciting trigger of chemotherapeutic agents. The present review aims to summarize the current knowledge of HVOD and PVOD and to describe both similarities as well as differences regarding both conditions.
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IgA nephropathy (IgAN) features variable renal pathology and a heterogeneous clinical course. Our aim was to search noninvasive biomarkers from urinary exosomes for IgAN patients; membrane nephropathy and minimal change disease were included as other glomerulopathy controls. Transmission electron microscopy and nanoparticle tracking analysis confirmed the size and morphology characteristic of urinary exosomes. ⋯ Exosomal CCL2 was correlated with tubulointerstitial inflammation and C3 deposition. High CCL2 levels at the time of renal biopsy were associated with subsequent deterioration in renal function. Thus, urinary exosomes and exosomal CCL2 mRNA are promising biomarkers reflecting active renal histologic injury and renal function deterioration in IgAN.