A Spatio-temporal Model for Detecting the Effect of Cocaine Use Disorder on Functional Connectivity.

Drug addiction can lead to many health-related problems and social concerns. Researchers are interested in the association between long-term drug usage and abnormal functional connectivity. Functional connectivity obtained from functional magnetic resonance imaging data promotes a variety of fundamental understandings in such association. Due to the complex correlation structure and large dimensionality, the modeling and analysis of the functional connectivity from neuroimage are challenging. By proposing a spatio-temporal model for multi-subject neuroimage data, we incorporate voxel-level spatio-temporal dependencies of whole-brain measurements to improve the accuracy of statistical inference. To tackle large-scale spatio-temporal neuroimage data, we develop a computational efficient algorithm to estimate the parameters. Our method is used to first identify functional connectivity, and then detect the effect of cocaine use disorder (CUD) on functional connectivity between different brain regions. The functional connectivity identified by our spatio-temporal model matches existing studies on brain networks, and further indicates that CUD may alter the functional connectivity in the medial orbitofrontal cortex subregions and the supplementary motor areas.

Chemerin/ChemR23 axis promotes inflammation of glomerular endothelial cells in diabetic nephropathy.

Diabetic nephropathy (DN) is characterized by inflammation of renal tissue. Glomerular endothelial cells (GEnCs) play an important role in inflammation and protein leakage in urine in DN patients. Chemerin and its receptor ChemR23 are inducers of inflammation. The aim of this study was to investigate the function of chemerin/ChemR23 in GEnCs of DN patients. Immunohistochemical staining and qRT-PCR were used to measure the expression of chemerin, ChemR23 and inflammatory factors in renal tissues of DN patients. Db/db mice were used as animal model. ChemR23 of DN mice was knocked down by injecting LV3-shRNA into tail vein. Inflammation, physiological and pathological changes in each group was measured. GEnCs were cultured as an in vitro model to study potential signalling pathways. Results showed that expression of chemerin, ChemR23 and inflammatory factors increased in DN patients and mice. LV3-shRNA alleviated renal damage and inflammation in DN mice. GEnCs stimulated by glucose showed increased chemerin, ChemR23 and inflammatory factors and decreased endothelial marker CD31. Both LV3-shRNA and SB203580 (p38 MAPK inhibitor) attenuated chemerin-induced inflammation and injury in GEnCs. Taken together, chemerin/ChemR23 axis played an important role in endothelial injury and inflammation in DN via the p38 MAPK signalling pathway. Suppression of ChemR23 alleviated DN damage.