Macrophages play a pivotal role in tissue fibrogenesis, which underlies the pathogenesis of many end-stage chronic inflammatory diseases. MicroRNAs are key regulators of immune cell functions, but their roles in macrophage's fibrogenesis have not been characterized. Here we show that IL-4 and IL-13 induce miR-142-5p and downregulate miR-130a-3p in macrophages; these changes sustain the profibrogenic effect of macrophages. In vitro, miR-142-5p mimic prolongs STAT6 phosphorylation by targeting its negative regulator, SOCS1. Blocking miR-130a relieves its inhibition of PPARγ, which coordinates STAT6 signalling. In vivo, inhibiting miR-142-5p and increasing miR-130a-3p expression with locked nucleic acid-modified oligonucleotides inhibits CCL4-induced liver fibrosis and bleomycin-induced lung fibrosis in mice. Furthermore, macrophages from the tissue samples of patients with liver cirrhosis and idiopathic pulmonary fibrosis display increased miR-142-5p and decreased miR-130a-3p expression. Therefore, miR-142-5p and miR-130a-3p regulate macrophage profibrogenic gene expression in chronic inflammation.

Phyllodes tumors of breast, even histologically diagnosed as benign, can recur locally and have metastatic potential. Histologic markers only have limited value in predicting the clinical behavior of phyllodes tumors. It remains unknown what drives the malignant progression of phyllodes tumors. We found that the expression of myofibroblast markers, a-smooth muscle actin (a-SMA), fibroblast activation protein (FAP), and stromal cell-derived factor-1 (SDF-1), is progressively increased in the malignant progression of phyllodes tumors. Microarray showed that miR-21 was one of the most significantly upregulated microRNAs in malignant phyllodes tumors compared with benign phyllodes tumors. In addition, increased miR-21 expression was primarily localized to a-SMA-positive myofibroblasts. More importantly, a-SMA and miR-21 are independent predictors of recurrence and metastasis, with their predictive value of recurrence better than histologic grading. Furthermore, miR-21 mimics promoted, whereas miR-21 antisense oligos inhibited, the expression of a-SMA, FAP, and SDF-1, as well as the proliferation and invasion of primary stromal cells of phyllodes tumors. The ability of miR-21 to induce myofibroblast differentiation was mediated by its regulation on Smad7 and PTEN, which regulate the migration and proliferation, respectively. In breast phyllodes tumor xenografts, miR-21 accelerated tumor growth, induced myofibroblast differentiation, and promoted metastasis. This study suggests an important role of myofibroblast differentiation in the malignant progression of phyllodes tumors that is driven by increased miR-21. Cancer Res; 74(16); 4341-52. Ó2014 AACR.

Biochar-based fertilizers have attracted increased attention, because biochar can improve the soil fertility, promote plant growth and crop yield. However, biochar-based controlled release nitrogen fertilizers (BCRNFs) still face problems because of the high cost, inefficient production technology, instability of nitrides, and the challenge associated with the controlled release of nutrients. In this study, we hydrothermally synthesised novel BCRNFs using urea-loaded biochar, bentonite and polyvinyl alcohol for controlled release of nutrients. Scanning electron microscopy and gas adsorption were conducted to identify the urea-loading and storage of bentonite in the inner pores of the biochar particles. X-ray diffraction, Fourier transform infrared spectroscopic and X-ray photoelectron spectroscopic studies demonstrated that strengthening the interactions among biochar, urea, and bentonite, helps control the moisture diffusion and penetration of bentonite, thereby leading to nutrient retention. The BCRNF showed significantly improved nutrient release characteristic compared with that of a mixture of biochar and urea. This urea-bentonite composite loaded with urea provides control over the release of nutrients stored in the biochar. BCRNF, especially those produced hydrothermally, can have potential applications in sustainable food security and green agriculture.