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This paper provides new insights into the potential therapeutic effects of vitamin E on COPD. The authors show that vitamin E relieves chronic obstructive pulmonary disease (COPD) by negatively regulating the EGFR/MAPK pathway and inhibiting COX2-mediated translocation of phosphorylated STAT3 to the nucleus. Moreover, overexpression of COX2 reverses the protective effect of vitamin E in a rat model of COPD.
miR-21-5p directly decreases levels of Jag1, which inhibits the Notch pathway and subsequently promotes the differentiation of adipose-derived stem cells into myelin-forming Schwann cells. Exploiting this signalling pathway may be an effective new method for the treatment of nerve injury.
Through analysis of the PD-L1 promoter, the authors describe two clear cell renal cell carcinoma (ccRCC) models that exhibit differential PD-L1 expression levels upon IFNγ and hypoxia stimulation. Mutant-VHL ccRCC cells display higher PD-L1 expression than wild-type-VHL ccRCC cells due to high basal HIF2α expression and a stronger response to IFNγ stimulation. Thus, mutant-VHL ccRCC cells are expected to respond well to immune checkpoint inhibitors.
The authors developed a deep learning model predictive of 1p/19q status from preoperative imaging in 555 lower-grade gliomas (LGG), and achieved an area under the curve (AUC) of 0.983 in the testing dataset. They reveal that developing deep learning imaging signatures could be a noninvasive tool for predicting molecular markers in LGG.
The authors barcoded glioma-initiating cells (GIC) using combinations of virally encoded fluorophores. GIC show a strong tendency to form clonal populations over as few as two passages. Combined with stem cell marker phenotyping and computational analysis, they could trace the fate of such populations. This model presents an approach for rapid assessment of newly established GIC to assess tumour-specific vulnerabilities.
This study demonstrates that lipopolysaccharide promotes activation of the JNK signaling pathway and endogenous TNF-α secretion in pulmonary macrophages, which facilitates lung fibroblast aerobic glycolysis and lactate production through PFKFB3 activation. These findings suggests that inflammation-metabolism interactions between lung macrophages and fibroblasts might play an essential role in lipopolysaccharide-induced pulmonary fibrosis.
The authors demonstrate that matrix metalloproteinase 11 (MMP11) expression in mononuclear inflammatory cells (predominantly macrophages) is an independent negative prognostic factor in breast cancer, whereas tumoral MMP11 expression is not associated with patient survival. This study also shows that MMP11-overexpressing macrophages promote the migration of HER2-positive breast cancer cells and monocyte recruitment through CCL2-CCR2 signaling, suggesting a pro-tumoral role of MMP11 in macrophages in HER2-positive breast cancer through interaction with cancer cells and other cells in the tumor microenvironment.
The authors explored the role of microRNA-155-5p (miR-155-5p) in childhood acute lymphoblastic leukemia (cALL). They found that miRNA-155-5p targets the E3 ubiquitin ligase CBL and inhibits its expression, reducing the ubiquitination and degradation of interferon regulatory factor 4, thus elevating expression of cyclin-dependent kinase 6. These findings suggest a basis for potential future therapeutic strategies for cALL.
Understanding of endothelial functions would be accelerated by methods for the specific isolation of these cells from archived human specimens. Here, the authors use the endothelial transcription factor Erg to isolate nuclei from mouse and human tissues, paving the way for high-throughput characterization of the function of endothelium in homeostasis and disease.
Diabetic cardiomyopathy is a serious diabetes-related cardiovascular complication, which is closely related to myocardial metabolic disorders, but there is no specific therapy currently. Renal denervation (RDN), a novel technique to remove renal sympathetic nerves, can reduce the overexpression of renal SGLT2 in diabetic rats, thereby promoting urinary glucose excretion and maintaining systemic glucose homeostasis. On this basis, RDN ameliorated diabetes-induced cardiac metabolic disorders and mitochondrial damages, ultimately preventing diabetes-induced cardiac dysfunction and pathological remodeling.
Fluvastatin, a cholesterol-lowering drug, radiosensitizes pancreatic cancer (PC) cells partly by inhibiting DNA damage response and/or autophagic flux. Fluvastatin also significantly suppresses intra-tumor radiation-induced fibrosis, as it inhibits radiation/TGF-β-induced activation of pancreatic stellate cells. Together, fluvastatin and radiation co-treatment may be a potential therapeutic approach against PC and warrants further clinical evaluation.
The authors examined the indirect effects of mesenchymal stem cells (MSCs) on spinal infusion through macrophages. They found that posterior spinal fusion is improved by placental growth factor (PlGF)-expressing MSCs, likely through attraction of macrophages and indution their M2 polarization, which in turn promotes the bone formation.
Cardiac hypertrophy is a common cardiovascular disease worldwide, and this study may provide novel potential therapeutic targets. The authors demonstrate that TINCR improves cardiac hypertrophy by acting as a competitive endogenous RNA for miR-211-3p and thus relieving its suppressive effects on the VEGFB-SDF-1α-CXCR4 signalling axis.
Sustained high circulating levels of fibroblast growth factor (FGF) 21 improve obesity/systemic insulin resistance and promote ketone body production as a second hepatic disposal system for excess free fatty acids. Liver-derived ketone bodies may be utilized for energy in skeletal muscle. The potential FGF21-related crosstalk between the liver and extrahepatic organs is a promising strategy against nonalcoholic fatty liver disease.
This study investigates the role of c-Abelson (c-Abl) kinase in neutrophil extracellular trap (NET) formation and inflammation during sepsis. The authors demonstrate that c-Abl kinase plays a pivotal role in NET formation, pulmonary formation of CXC chemokines and lung injury in sepsis. Authors conclude that targeting c-Abl kinase might be a useful strategy to ameliorate local and systemic inflammation in sepsis.
A proposed regulatory model of FABP4 in Hcy-induced macrophage inflammation in atherosclerosis ofApoE−/−mice. FABP4 activates the JAK2/STAT2 pathway via Rap1a in Hcy-induced macrophage inflammatory response and atherosclerosis in ApoE−/− mice, which is attributed to Rap1a-dependent promotion of the c-Src phosphorylation at Tyr416 and membrane translocation. SOCS1 has a negative regulatory role in FABP4-dependent activation of the JAK2/STAT2 pathway and Rap1a in macrophage inflammatory response induced by Hcy.
Aggrecan degradation by ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) is essential to cartilage destruction in osteoarthritis, but its expression profile and regulation are unclear. The authors show overexpression of ADAMTS4 in osteoarthritis synovium and synergistic upregulation by interleukin-1α, tumor necrosis factor-α, and transforming growth factor-β in osteoarthritis synovial fibroblasts. These findings suggest that concurrent therapy with an anti-TNF-α drug and inhibitor(s) may be useful for prevention against aggrecan degradation in OA.