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Intractable pulmonary fibrosis is a major cause of death in patients with acute respiratory distress syndrome (ARDS), while lipopolysaccharide (LPS) is an important etiological factor in ARDS and pulmonary fibrosis. This study provides convincing evidence that LPS promote lung fibroblast proliferation through autophagy inhibition via activation of the PI3K-Akt-mTOR pathway. Intervention by targeting inhibition of lung fibroblast autophagy may be a constructive means for treatment of pulmonary fibrosis.
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.
In this paper the authors outline the known neuropathology of mild traumatic brain injury (mTBI). They employed immunohistochemistry and gene expression profiling techniques in two post-mortem cases in order to propose markers of DNA damage as the driver of pathology and symptoms after mTBI.
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.
The authors report that pathogenic TDP-43 is increased and closely associated with mitochondria in degenerating skeletal muscles of patients with inclusion body myositis, while key subunits of mitochondrial oxidative phosphorylation complexes I and III are reduced, implying a potential role of mitochondria and associated TDP-43 for disease pathogenesis.
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
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.
The authors identified and compared the primary and contributing diagnoses for people with primary age-related tauopathy (PART) to those with Alzheimer’s disease neuropathologic change (ADNP). Clinicians diagnose AD less frequently in those with PART, recognizing a distinction in the clinical presentation between PART and ADNP.
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 investigated the effects and mechanism of IL-10 in renal ischemia-reperfusion injury (IRI). Compared to wild-type mice with IRI, IL-10 knockout (IL-10 KO) mice with IRI demonstrated decreased renal function, increased mRNA expressions of the pro-inflammatory cytokines, and increased expression of the pro-apoptosis factors. Our findings demonstrate that IL-10 suppresses the production of pro-inflammatory cytokines, renal dysfunction and the expression of pro-apoptosis factors after IRI.
Targeting splenic macrophages with immunosuppressive microRNA is a potential therapeutic strategy for sepsis. Interference of splenic macrophages by miR-146a-expressing plasmid and polyethyleneimine complex modulates the Toll-like receptor-related immunity, which results in the amelioration of excessive inflammation, multiple organ injury, and even death due to sepsis.
Doxorubicin inactivates the EGFR/Src/HMG-CR pathway, and decreases levels of both cholesterol and lipid rafts. Simvastatin enhances doxorubicin-induced cell death but cholesterol attenuates it. The anti-cancer effect of doxorubicin is attenuated in cholesterol-high diet-fed mice. Therefore, cholesterol control may be combined with treatment to enhance doxorubicin efficacy and reduce its side effects.
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.