Volume 99 Issue 6, June 2019

The present study reveals that lipotoxicity causes defective mitophagy and excessive mitochondrial reactive oxygen species accumulation. In turn, both events trigger NLRP3 inflammasome activation in fatty acid-overloaded primary hepatocytes. The novel insight advances the understanding of how fatty acids elicit lipotoxicity through oxidant stress and autophagy in mitochondria during progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis.

The authors show that fibroblast activation protein (FAP) induces the tumor promoting phenotype of fibroblasts through secretion of several cytokines. It activates tumor cells, recruits macrophages and polarizes them into the M2 phenotype. FAP may therefore be a valuable prognostic marker and specific target of anti-cancer therapy.

There are adjacent TCF/LEF and SMAD consensus binding sites in cyclin D2 and Bmp4 promoters. TCF7, LEF1 and activated SMADs enhance while TCF7L2 inhibits cyclin D2 and Bmp4 expression. Wnt activation increases TCF7 and LEF1 to replace TCF7L2 in these promoters for transcriptional activation and thus promotes cardiomyocyte proliferation.

This study reveals the role of Parkin-dependent apoptosis in lipopolysaccharideinduced acute respiratory distress syndrome (ARDS). Polydatin, an herbal resveratrol-related glucoside, significantly activates Parkin-dependent mitophagy to protect against mitochondria-dependent apoptosis and lung injury. Thus, polydatin may be useful for the treatment of ARDS.

We revealed that the pathogenesis of mTORi-induced lung injury may be involved in alveolar epithelial injury via lipid metabolic stress associated with downregulated PPAR-γ expression. Focusing on the relationship between lipid metabolic stress and alveolar epithelial injury represents a potentially novel approach to the study of pulmonary damage.

Osteoblast-specific cell-surface molecules are believed to be involved in the molecular modulation of bone remodeling. The authors describe a unique cell-surface molecule, A7 antigen, that is specifically expressed in cells of osteoblast lineage. Cross-linking of cell-surface A7 antigen stimulates osteoclastogenesis and markedly suppresses calcification. A7 antigen appears to be a novel recruitment molecule for osteoclasts and trigger of calcification

Continuously cultivated iPSCs with chromosome 21 trisomy spontaneously reverted to normal diploids. This trisomy rescue occurred without genetic manipulation, chemical treatment, or exposure to irradiation. The revertant cells can serve as a reference for drug screening and as raw materials for regenerative medicine and cell-based therapy.

Clear cell renal cell carcinoma (ccRCC) is characterized by activation of hypoxia-inducible factors and enhanced aerobic glycolysis. In this study, the authors found that ccRCC maintains high levels of fructose-1,6-bisphosphate (FBP) through the downregulation of aldolase B. In turn, FBP regulates the redox status of the tumor by suppressing NADPH oxidase isoform NOX4 activity. Thus, aldolase B and FBP are critical regulators of reactive oxygen species and contribute to tumor progression.