Effective treatments for neurodegenerative diseases need to be developed. MiR132 is abundantly expressed in the brain, and it modulates neuron morphology and plays a key role in maintaining neuron survival. Regulating miR132 can effectively improve the symptoms of Alzheimer's disease. It can also reduce cell death after cerebral hemorrhage, improve the microenvironment of hematoma lesions and provide a certain protective effect from brain damage after cerebral ischemia. MiR132 has great potential in the treatment of cerebral ischemia and Alzheimer's disease. To prevent the decline of miR132 of miR132 levels in the blood, we used mouse and rat models of Alzheimer's disease with ischemic brain injury, and then delivered Wheat germ agglutinin (WGA)-NPs-miR132 intranasally to treat neurological damage after cerebral ischemia. Synaptic protein expression levels in Alzheimer's mouse models increased significantly after administration. We propose that, nasal delivery of WGA-NPs-miR132 is an interesting novel therapeutic approach for the treatment of neurodegenerative diseases.
High‐fat diet (HFD) induced hepatic endoplasmic reticulum (ER) stress drives insulin resistance (IR) and steatosis. NK cells in adipose tissue play an important role in the pathogenesis of IR in obesity. Whether NK cells in the liver can induce hepatic ER stress and thus promote IR in obesity is still unknown. We demonstrate that HFD‐fed mice display elevated production of proinflammatory cytokine osteopontin (OPN) in hepatic NK cells, especially in CD49a+DX5– tissue‐resident NK (trNK) cells. Obesity‐induced ER stress, IR, and steatosis in the liver are ameliorated by ablating NK cells with neutralizing antibody in HFD‐fed mice. OPN treatment enhances the expression of ER stress markers, including p‐PERK, p‐eIF2, ATF4, and CHOP in both murine liver tissues and HL‐7702, a human liver cell line. Pretreatment of HL‐7702 cells with OPN promotes hyperactivation of JNK and subsequent decrease of tyrosine phosphorylation of insulin receptor substrate‐1 (IRS‐1), resulting in impaired insulin signaling, which can be reversed by inhibiting ER stress. Collectively, we demonstrate that hepatic NK cells induce obesity‐induced hepatic ER stress, and IR through OPN production.
Abstract. The co-association (CA) matrix was previously introduced to combine multiple partitions. In this paper, we analyze the CA matrix, and address its difference from the similarity matrix using Euclidean distance. We also explore how to find a proper and better algorithm to obtain the final partition using the CA matrix. To get more robust and reasonable clustering ensemble results, a new hierarchical clustering algorithm is proposed by developing a novel concept of normalized edges to measure the similarity between clusters. The experimental results of the proposed approach are compared with those of some single runs of well-known clustering algorithms and other ensemble methods and the comparison clearly demonstrates the effectiveness of our algorithm.
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