Overexpression of a steroid receptor-binding protein bearing the regulator of the G-protein signaling domain suppresses migration and invasion of human endometrial stromal cells stimulated by 17ß-estradiol.

OBJECTIVE: Endometriosis is an estrogen-dependent disease, a steroid receptor-binding protein bearing the regulator of the G-protein signaling domain (SRB-RGS) can suppress the estrogen receptors-mediated transcriptional activities. We sought to determine whether overexpression of SRB-RGS suppresses the migration and invasion ability of endometrial stromal cells stimulated by 17ß-estradiol (E2). STUDY DESIGN: Endometrial stromal cells were obtained from endometriosis patients. SRB-RGS was overexpressed in the cells stimulated by E2. The migration and invasion ability of the cells were measured by migration assay and invasion assay, respectively. Western blot analysis was done to test the expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). RESULTS: Overexpression of SRB-RGS suppressed the migration and invasion ability of the stromal cells stimulated by E2; it also suppressed the expression of MMP-9 and VEGF, while the expression of TIMP-1 was increased. CONCLUSIONS: Overexpression of SRB-RGS suppresses the migration and invasion ability of the E2-stimulated endometrial stromal cells. The molecular mechanism is the reduced expression of MMP-9 and VEGF, and the increased expression of TIMP-1. These findings suggest that the coding gene of SRB-RGS is a promising target gene for endometriosis gene therapy.

Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats.

AIM: To investigate the therapeutic effects of lutein against non-alcoholic fatty liver disease (NAFLD) and the related underlying mechanism. METHODS: After 9 d of acclimation to a constant temperature-controlled room (20 °C-22 °C) under 12 h light/dark cycles, male Sprague-Darley rats were randomly divided into two groups and fed a standard commercial diet (n = 8) or a high-fat diet (HFD) (n = 32) for 10 d. Animals receiving HFD were then randomly divided into 4 groups and administered with 0, 12.5, 25, or 50 mg/kg (body weight) per day of lutein for the next 45 d. At the end of the experiment, the perinephric and abdominal adipose tissues of the rats were isolated and weighed. Additionally, serum and liver lipid metabolic condition parameters were measured, and liver function and insulin resistance state indexes were assessed. Liver samples were collected and stained with hematoxylin eosin and Oil Red O, and the expression of the key factors related to insulin signaling and lipid metabolism in the liver were detected using Western blot and real-time polymerase chain reaction analyses. RESULTS: Our data showed that after being fed a high-fat diet for 10 d, the rats showed a significant gain in body weight, energy efficiency, and serum total cholesterol (TC) and triglyceride (TG) levels. Lutein supplementation induced fat loss in rats fed a high-fat diet, without influencing body weight or energy efficiency, and decreased serum TC and hepatic TC and TG levels. Moreover, lutein supplementation decreased hepatic levels of lipid accumulation and glutamic pyruvic transaminase content, and also improved insulin sensitivity. Lutein administration also increased the expression of key factors in hepatic insulin signaling, such as insulin receptor substrate-2, phosphatidylinositol 3-kinase, and glucose transporter-2 at the gene and protein levels. Furthermore, high-dose lutein increased the expression of peroxisome proliferators activated receptor-α and sirtuin 1, which are associated with lipid metabolism and insulin signaling. CONCLUSION: These results demonstrate that lutein has positive effects on NAFLD via the modulation of hepatic lipid accumulation and insulin resistance.

Alkaloids from the bulbs of Lycoris longituba and their neuroprotective and acetylcholinesterase inhibitory activities.

Three novel alkaloids (1-3), together with nineteen known ones (4-22), were isolated from the bulbs of Lycoris longituba. Their structures were elucidated on the basis of extensive spectroscopic analyses, which belong to several Amaryllidaceae alkaloid skeletons. Among them, the harmane-type alkaloids (the new compound 1 and the known compounds 5, 6 and 7) were found for the first time from Lycoris genus. The isolates were tested for their neuroprotective activities against CoCl2, H2O2 and Aß25-35-induced SH-SY5Y cell injuries, and the majority of them exhibited neuroprotective activities of different degrees. The acetylcholinesterase (AChE) inhibitory activities of the isolated alkaloids were also evaluated, while compounds 12, 14-20 and 22 exhibited extremely significant AChE inhibitory activities.

Melatonin reduces the impairment of axonal transport and axonopathy induced by calyculin A.

Previous studies have reported that calyculin A (CA), a selective inhibitor of protein phosphatase (PP)-2A and PP-1, impairs axonal transport in neuroblastoma N2a cells. Melatonin prevents Alzheimer-like hyperphosphorylation of cytoskeletal proteins and the impairment of spatial memory retention induced by CA. In this study, we tested the effects of melatonin on the impairment of axonal transport induced by CA in neuroblastoma N2a cells. We found that melatonin protected the cells from CA-induced toxicity in metabolism and viability as well as hyperphosphorylation of tau and neurofilaments. Furthermore, melatonin partially reversed the CA-induced phosphorylation of the catalytic subunit of PP-2A at tyrosine 307, a crucial site that negatively regulates the activity of PP-2A, and reduced the levels of malondialdehyde and the activity of superoxide dismutase, which are markers of oxidative stress. Melatonin also significantly reversed the CA-induced impairment of axonal transport. These results suggest that melatonin may have a role in protecting against the CA-induced impairment of axonal transport by modulating the activity of PP-2A and oxidative stress.

Basic fibroblast growth factor gene transfection to enhance the repair of avascular necrosis of the femoral head.

OBJECTIVE: To explore a new method for the therapy of avascular necrosis of the femoral head. METHOD: The recombinant plasmid pCD-rbFGF was mixed with collagen and was implanted in the necrotic femoral head. Expression of basic fibroblast growth factor (bFGF) was examined by RT-PCR and immunohistochemical method. Repair of the femoral head was observed by histological and histomorphometric analysis. RESULT: Expression of bFGF was detected in the femoral head transfected with bFGF gene, indicating significant increase of angiogenesis 2 weeks after gene transfection and increased new bone formation 8 weeks after gene transfection on histomorphometric analysis (P< 0.01). CONCLUSION: Transfection of bFGF gene enhances bone tissue angiogenesis. Repair in osteonecrosis would be accelerated accordingly.