Microbial infection promotes amyloid pathology in a mouse model of Alzheimer's disease via modulating γ-secretase.

Microbial infection as a type of environmental risk factors is considered to be associated with long-term increased risk of dementia, including Alzheimer's disease (AD). AD is characterized by two neuropathologically molecular hallmarks of hyperphosphorylated tau and amyloid-ß (Aß), the latter generated by several biochemically reactive enzymes, including γ-secretase. However, how infectious risk factors contribute to pathological development of the AD core molecules remains to be addressed. In this work, we utilized a modified herpes simplex virus type 1 (mHSV-1) and found that its hippocampal infection locally promotes Aß pathology in 5 × FAD mice, the commonly used amyloid model. Mechanistically, we identified HSV-1 membrane glycoprotein US7 (Envelope gI) that interacts with and modulates γ-secretase and consequently facilitates Aß production. Furthermore, we presented evidence that adenovirus-associated virus-mediated locally hippocampal overexpression of the US7 aggravates Aß pathology in 5 × FAD mice. Collectively, these findings identify a herpesviral factor regulating γ-secretase in the development and progression of AD and represent a causal molecular link between infectious pathogens and neurodegeneration.

[Studies on chemical constituents of Zhuang medicine Excoecaria venenata and their cytotoxic activity].

Fourteen compounds were isolated from 95% ethanol extract by silica gel, MCI, and ODS column chromatography. These compounds were respectively identified as quercetin (1), kaempferol (2), (+)-catechin (3), fraxin (4), protocatechuic acid (5), gallic acid (6), methyl gallate (7), ethyl gallate (8), apocynol A (9), baccatin (10), cerevisterol (11), ellagic acid (12), 3, 3',4'-tri-0-methylellagic acid(13) and N-benzoyl-L-phenylalaninyl-N-benzoyl-L-phenylalaninate(14) by analyzing their spectral data and comparing with the previously reported literatures. Except for gallic acid (6), all other compounds were isolated from this plant for the first time. Compounds 1, 2 and 6 showed moderate anti-proliferation activities on tumor cells.

Simultaneous treatment of renal cysts and stones with single-session retroperitoneoscopic renal cyst decortication and retroperitoneoscopy-assisted percutaneous nephrolithotomy.

INTRODUCTION: To determine the safety and efficacy of single-session retroperitoneoscopic renal cyst decortication in conjunction with retroperitoneoscopy-assisted percutaneous nephrolithotomy (PCNL) for simultaneous treatment of renal cysts and stones. PATIENTS AND METHODS: We enrolled 15 patients (10 men and 5 women, mean age 41 years), who underwent one-stage retroperitoneoscopic renal cyst decortication and retroperitoneoscopy-assisted PCNL between January 2008 and May 2009 for symptomatic renal cysts and concomitant large kidney stones (mean stone area 6.6 cm(2)). Intraoperative blood loss, duration of operation, and postoperative complications were evaluated. Median follow-up time was 22 months (range 12-26). RESULTS: Average total operative time was 83 ± 12 min and mean duration of PCNL was 45 ± 5 min. Mean estimated blood loss was 80 ± 21 ml. A plain abdominal radiograph revealed an absence of residual stones in all cases. No cyst recurrence occurred within the follow-up period. The mean pre- and postoperative pain score was 7.3 ± 0.8 and 2.8 ± 0.6, respectively. All patients resumed ambulatory activities on the first postoperative day. No severe complications related to the procedure were encountered. CONCLUSION: The combined laparoscopic approach for simultaneous treatment of renal cysts and stones is safe and feasible. These results encourage further studies to determine long-term outcomes of this combined surgery.