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ABSTRACTHigh-fat diet (HFD) can cause obesity, inducing dysregulation of the visceral adipose tissue (VAT). This study aimed to explore potential biological pathways and hub genes involved in obese VAT, and for that, bioinformatic analysis of multiple datasets was performed. The expression profiles (GSE30247, GSE167311 and GSE79434) were downloaded from Gene Expression Omnibus. Overlapping differentially expressed genes (ODEGs) between normal diet and HFD groups in GSE30247 and GSE167311 were selected to run protein–protein interaction network, GO and KEGG analysis. The hub genes in ODEGs were screened by Cytoscape software and further verified in GSE79434 and obese mouse model. A total of 747 ODEGs (599 up-regulated and 148 down-regulated) were screened, and the GO and KEGG analysis showed that the up-regulated ODEGs were significantly enriched in inflammatory response and extracellular matrix receptor interaction pathways. On the other hand, the down-regulated ODEGs were involved in metabolic pathways; however, there were no significant KEGG pathways. Furthermore, six hub genes, Mki67, Rac2, Itgb2, Emr1, Tyrobp and Csf1r were acquired. These pathways and genes were verified in GSE79434 and VAT of obese mice. This study revealed that HFD induced VAT expansion, inflammation and fibrosis, and the hub genes could be used as therapeutic biomarkers in obesity.

The chelation adsorption behavior of a salicylic acid-type composite ASA-PGMA/SiO2 for rare earth ions of the rare earth ore mud leaching solution in Mianning was studied in the present work. The effect of the reaction temperature and medium pH on adsorption properties of the ASA-PGMA/SiO2 particle was examined. The concentrations of REEs were determined by ICP-MS. The results showed that the ASA-PGMA/SiO2 possessed strong chelation adsorption ability for rare earth ions. The reaction temperature was 50°C, the adsorption properties of the composite were the best and the adsorption rate of rare earth ions reached above 90%. In the pH range where the hydrolysis of rare earth ions was inhibited, an increase in the pH value of the medium strengthened the chelation adsorption ability of the ASA-PGMA/SiO2 particle for rare earth ions. The rare earth ions desorption from the ASA-PGMA/SiO2 particle is effective when using 0.2mol/L of hydrochloric acid solution as the eluent.

Atherosclerotic disease is a leading cause of morbidity and mortality in developed countries, and oxidized LDL (OxLDL) plays a key role in the formation, rupture, and subsequent thrombus formation in atherosclerotic plaques. In the current study, anti-mouse OxLDL polyclonal antibody and nonspecific IgG antibody were conjugated to polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, and a carotid perivascular collar model in apolipoprotein E-deficient mice was imaged at 7.0 Tesla MRI before contrast administration and at 8 h and 24 h after injection of 30 mg Fe/kg. The results showed MRI signal loss in the carotid atherosclerotic lesions after administration of targeted anti-OxLDL-USPIO at 8 h and 24 h, which is consistent with the presence of the nanoparticles in the lesions. Immunohistochemistry confirmed the colocalization of the OxLDL/macrophages and iron oxide nanoparticles. The nonspecific IgG-USPIO, unconjugated USPIO nanoparticles, and competitive inhibition groups had limited signal changes (p < 0.05). This report shows that anti-OxLDL-USPIO nanoparticles can be used to directly detect OxLDL and image atherosclerotic lesions within 24 h of nanoparticle administration and suggests a strategy for the therapeutic evaluation of atherosclerotic plaques in vivo.

Kallistatin is a serine proteinase inhibitor that has been shown to reduce joint swelling and to inhibit inflammation in a rat model of arthritis. In this study, we investigated the effect and mechanisms of kallistatin on cardiac function after myocardial ischemia–reperfusion (I/R) injury. The human kallistatin gene in an adenoviral vector was delivered locally into rat heart 4 days before 30-min ischemia followed by 24-hr reperfusion. Kallistatin gene transfer significantly reduced myocardial infarct size and left ventricle end-diastolic pressure and improved cardiac contractility. Kallistatin significantly reduced I/R-induced cardiomyocyte apoptosis as identified by TUNEL and Hoechst staining, DNA laddering, cell viability, and caspase-3 activity in ischemic myocardium and in primary cultured cardiomyocytes. Kallistatin also reduced intramyocardial monocyte/macrophage and neutrophil accumulation in conjunction with decreased expression of monocyte chemoattractant protein-1, tumor necrosis factor-α, and intercellular adhesion molecule-1. Kallistatin delivery promoted cardiac endothelial nitric oxide synthase activation and increased nitric oxide (NO) formation, but inhibited NADH oxidase activity, p22phox expression, and superoxide production. Moreover, kallistatin reduced the phosphorylation of apoptosis signal-regulating kinase-1 and mitogen-activated protein kinases (MAPKs), but increased Akt and glycogen synthase kinase-3β phosphorylation. The effects of kallistatin on cardiac function, oxidative stress, and these signal transduction events were all blocked by Nω-nitro-L-arginine methyl ester. These results indicate a novel role of kallistatin in cardiac protection after I/R injury through increased NO formation and Akt–glycogen synthase kinase-3β signaling and suppression of oxidative stress and MAPK activation.

Stroke-induced neurological deficits and mortality are often associated with timing of treatment after the onset of stroke. We showed that local delivery of the human tissue kallikrein gene into rat brain immediately after middle cerebral artery occlusion (MCAO) exerts neuroprotection. In this study, we investigated the effect of systemic delivery of the kallikrein gene 8 hr after MCAO. Expression of recombinant human tissue kallikrein after gene transfer was identified in the ischemic brain region and blood vessels. Intravenous injection of adenovirus encoding the kallikrein gene significantly reduced neurological deficit scores 2 and 7 days after gene transfer. Kallikrein gene transfer also reduced ischemia–reperfusion (I/R)-induced cerebral infarction and promoted the survival and migration of glial cells from penumbra to the ischemic core from 3 to 14 days after gene delivery. Kallikrein reduced I/R-induced apoptosis of neuronal cells and inhibited inflammatory cell accumulation in the ischemic brain. These effects were blocked by the kinin B2 receptor antagonist icatibant. In addition, kallikrein enhanced angiogenesis and promoted neurogenesis after I/R and the stimulatory effect of kinin on neuronal cell proliferation was confirmed in primary cultured neuronal cells. The protective effects of kallikrein, through the kinin B2 receptor, were accompanied by increased cerebral nitric oxide and Bcl-2 levels, Akt phosphorylation, and reduced NAD(P)H oxidase activity, superoxide production, Bax levels, and caspase-3 activity. These results indicate that delayed systemic administration of the kallikrein gene after onset of stroke protects against ischemic brain injury by inhibiting apoptosis and inflammation and by promoting angiogenesis and neurogenesis.