3 research outputs found
Adaptive Graph Construction for Isomap Manifold Learning
Isomap is a classical manifold learning approach that preserves geodesic distance of nonlinear data sets. One of the main drawbacks of this method is that it is susceptible to leaking, where a shortcut appears between normally separated portions of a manifold. We propose an adaptive graph construction approach that is based upon the sparsity property of the â„“1 norm. The â„“1 enhanced graph construction method replaces k-nearest neighbors in the classical approach. The proposed algorithm is first tested on the data sets from the UCI data base repository which showed that the proposed approach performs better than the classical approach. Next, the proposed approach is applied to two image data sets and achieved improved performances over standard Isomap
Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140
Abstract
Osteoarthritis (OA) is characterized by the progressive destruction of articular cartilage, which is involved in the imbalance between extracellular matrix (ECM) synthesis and degradation. MicroRNA-140-5p (miR-140) is specifically expressed in cartilage and plays an important role in OA-induced matrix degradation. The aim of this study was to investigate (1) whether intra-articular injection of melatonin could ameliorate surgically induced OA in mice and (2) whether melatonin could regulate matrix-degrading enzymes at the posttranscriptional level by targeting miR-140. In an in vitro OA environment induced by interleukin-1 beta (IL-1β), melatonin treatment improved cell proliferation of human chondrocytes, promoted the expression of cartilage ECM proteins (e.g., type II collagen and aggrecan), and inhibited the levels of IL-1β-induced proteinases, such as matrix metalloproteinase 9 (MMP9), MMP13, ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), and ADAMTS5. Both the microarray and polymerase chain reaction (PCR) experiments revealed that miR-140 was a melatonin-responsive microRNA and melatonin upregulated miR-140 expression, which was suppressed by IL-1β stimulation. In vivo experiments demonstrated that intra-articular injection of melatonin prevented disruptions of cartilage matrix homeostasis and successfully alleviated the progression of surgery-induced OA in mice. Transfection of miR-140 antagomir completely counteracted the antiarthritic effects of melatonin by promoting matrix destruction. Our findings demonstrate that melatonin protects the articular cartilage from OA-induced degradation by targeting miR-140, and intra-articular administration of melatonin may benefit patients suffering from OA