CD93 regulates breast cancer growth and vasculogenic mimicry through the PI3K/AKT/SP2 signaling pathway activated by integrin ß1.

In women, breast cancer (BC) accounts for 7%-10% of all cancer cases and is one of the most common cancers. To identify a new method for treating BC, the role of CD93 and its underlying mechanism were explored. MDA-MB-231 cells were used in this study and transfected with si-CD93, si-MMRN2, oe-CD93, si-integrin ß1, or oe-SP2 lentivirus. After MDA-MB-231 cells were transfected with si-NC or si-CD93, they were injected into nude mice by subcutaneous injection at a dose of 5 × 106/mouse to construct a BC animal model. The expression of genes and proteins and cell migration, invasion and vasculogenic mimicry were detected by RT‒qPCR, western blot, immunohistochemistry, immunofluorescence, Transwell, and angiogenesis assays. In pathological samples and BC cell lines, CD93 was highly expressed. Functionally, CD93 promoted the proliferation, migration, and vasculogenic mimicry of MDA-MB-231 cells. Moreover, CD93 interacts with MMRN2 and integrin ß1. Knockdown of CD93 and MMRN2 can inhibit the activation of integrin ß1, thereby inhibiting the PI3K/AKT/SP2 signaling pathway and inhibiting BC growth and vasculogenic mimicry. In conclusion, the binding of CD93 to MMRN2 can activate integrin ß1, thereby activating the PI3K/AKT/SP2 signaling pathway and subsequently promoting BC growth and vasculogenic mimicry.

Association between the maternal serum levels of 19 eicosanoids and pre-eclampsia.

OBJECTIVE: To investigate whether serum levels of 19 eicosanoids are associated with pre-eclampsia. METHODS: A case-control study was performed using data for pregnant women with pre-eclampsia, normotensive pregnant women, and nonpregnant women, for all of whom serum samples had been collected at a hospital in Shanghai, China, between December 2012 and December 2013. Ultra-performance liquid chromatography-tandem mass spectrometry was used to measure the serum levels of 19 eicosanoids. RESULTS: Overall, 49 pregnant women with pre-eclampsia, 26 normotensive pregnant women, and 14 nonpregnant women were included. Women with pre-eclampsia had significantly higher serum levels of 11,12-epoxyeicosatrienoic acid (11,12-EET), the hydroxyeicosatetraenoic acids 5-HETE, 8-HETE, 12-HETE, and 15-HETE, and leukotriene B4 than did women with a normal pregnancy and nonpregnant women, both before and after the onset of pre-eclampsia (P<0.01 for all comparisons). Women with severe pre-eclampsia had significantly higher serum levels of 5-HETE, 15-HETE, and leukotriene B4 than did women with mild pre-eclampsia, women with a normal pregnancy, and nonpregnant women (P<0.01 for all comparisons). CONCLUSION: The eicosanoids 11,12-EET, 5-HETE, 8-HETE, 12-HETE, 15-HETE, and leukotriene B4 might play important parts in the occurrence and development of pre-eclampsia.

Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress.

The aim of this study was to investigate pathophysiological alterations and oxidative stress in various stages of streptozotocin (STZ)­induced diabetes mellitus (DM) in rats. Male Sprague-Dawley rats (120) were randomized into DM and control groups. Body mass, plasma glucose, glycated hemoglobin (HbA1c), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, as well as aldose reductase (AR) activities, in brain tissue and serum were determined. Electron microscopy was used to observe neuron and vessel changes in the brain. In STZ­treated rats, blood glucose, low density lipoproteins, triglycerides and total cholesterol levels increased 1.43­3.0­fold and high density lipoprotein, HbA1c and insulin sensitivity index increased 1.1­1.23­fold compared with control. At week 16 following treatment, DM rat serum H2O2 concentration was increased, indicating oxidative stress and mRNA levels of GPx and SOD were 2­fold higher than the control. Protein GPx and SOD levels were reduced (P<0.01). DM rats were identified to exhibit early irregular glomerular capillary basement membrane thickening and vacuolization in the mitochondria and epithelial cells. Neuron cells and blood vessels in the DM rat brains became increasingly abnormal over time with altered Golgi bodies, mitochondria and endoplasmic reticulum cisterns, concurrent with SOD inactivation and AR protein accumulation. Disease progression in rats with STZ­induced DM included brain pathologies with vascular and neuron cell abnormalities, associated with the reduction of SOD, CAT and GPx activities and also AR accumulation.