Molecular Basis of Inhibitory Activities of Berberine against Pathogenic Enzymes in Alzheimer's Disease

The natural isoquinoline alkaloid berberine possesses potential to treat Alzheimer's disease (AD) by targeting multiple pathogenic factors. In the present study, docking simulations were performed to gain deeper insights into the molecular basis of berberine's inhibitory effects against the important pathogenic enzymes of AD, that is, acetylcholinesterase, butyrylcholinesterase, and two isoforms of monoamine oxidase. It was found that the theoretical binding affinities of berberine to the four enzymes are very close to the experimental values, which verify the methodology. Further inspection to the binding modes found that hydrophobic interactions between the hydrophobic surface of berberine and neighboring hydrophobic residues are the principal forces contributing to the ligand-receptor interactions. Although berberine cation also has potential to form electrostatic interaction with neighboring residues, it is interesting to find that electrostatic force is excluded in the four cases unexpectedly. These results have important implications for the berberine-based anti-AD drug design

Alzheimer's Disease and Risk of Hip Fracture: A Meta-Analysis Study

Background. Alzheimer's disease (AD) is the most common cause of dementia in the elderly population. Growing evidence supports that AD patients are at high risk for hip fracture, but the issue remains questionable. The purpose of the present study is to perform a meta-analysis to explore the association between AD and risk of hip fracture. Considering that bone mineral density (BMD) acts as a strong predictor of bone fracture, we also studied the hip BMD in AD patients. Methods. We searched all publications in Medline, SciVerse Scopus, and Cochrane Library published up to January 2012 about the association between AD and hip fracture or hip BMD. Results. There are 9 studies included in the meta-analysis. The results indicate that AD patients are at higher risk for hip fracture (OR and 95% CI fixed: ES = 2.58, 95% CI = [2.03, 3.14]; dichotomous data: summary OR = 1.80, 95% CI = [1.54, 2.11]) than healthy controls. Further meta-analysis showed that AD patients have a lower hip BMD (summary SMD = −1.12, 95% CI = [−1.34, −0.90]) than healthy controls. Conclusions. It was found that in comparison with healthy controls AD patients are at higher risk for hip fracture and have lower hip BMD

A Meta-Analysis of Tea Drinking and Risk of Parkinson's Disease

Background. Many studies have reported an association between tea drinking and Parkinson's disease (PD). Our purpose is to summarize the available information and evaluate the risk of PD associated with tea drinking. Methods. We searched all publications in English language on the association of tea drinking and PD risk published up to December 2010. The pooled analysis was performed with Review Manager 5.0. Results. In total, eight articles including 1418 cases and 4250 controls were included in the meta-analysis. The pooled odds ratio (95% CI) was 0.85 (0.74–0.98), which suggests the protective effect of tea drinking in PD risks. Moreover, the summary OR (OR: 0.83, 95% CI = 0.69–0.99) for drinkers of ≤1 cup of tea per day versus nonconsumers and that (OR: 0.96, 95% CI = 0.73–1.27) for drinkers of >1 cups of tea per day versus nonconsumers showed that there was not an apparent dose-response relationship. No indication for publication bias was found. Conclusions. This meta-analysis showed that tea drinking can lower the risk of PD, while no apparent dose-response relationship was found. Further effort is needed to fully understand the mechanism underlying the beneficial effect of tea consumption in lowering PD risk

Selective thermal emission and infrared camouflage based on layered media

Infrared camouflage based on artificial thermal metasurfaces has recently attracted significant attention. By eliminating thermal radiation differences between the object and the background, it is possible to hide a given object from infrared detection. Infrared camouflage is an important element that increases the survivability of aircraft and missiles, by reducing target susceptibility to infrared guided threats. Herein, a simple and practicable design is theoretically presented based on a multilayer film for infrared stealth, with distinctive advantages of scalability, flexible fabrication, and structural simplicity. The multilayer medium consists of silicon substrate, carbon layer and zinc sulfide film, the optical properties of which are determined by transfer matrix method. By locally changing the thickness of the coating film, the spatial tunability and continuity in thermal emission are demonstrated. A continuous change of emissive power is further obtained and consequently implemented to achieve thermal camouflage functionality. In addition, other functionalities, like thermal illusion and thermal coding, are demonstrated by thickness-engineered multilayer films

Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery

Ligand-protein mapping was found to follow a power law and the preferential attachment principle, leading to the identification of the molecules, mostly nucleotide-containing compounds, that are likely to have evolved earliest

Reduced expression of SMAD4 in gliomas correlates with progression and survival of patients

<p>Abstract</p> <p>Background</p> <p>To examine the expression of SMAD4 at gene and protein levels in glioma samples with different WHO grades and its association with survival.</p> <p>Methods</p> <p>Two hundreds fifty-two glioma specimens and 42 normal control tissues were collected. Immunochemistry assay, quantitative real-time PCR and Western blot analysis were carried out to investigate the expression of SMAD4. Kaplan-Meier method and Cox's proportional hazards model were used in survival analysis.</p> <p>Results</p> <p>Immunohistochemistry showed that SMAD4 expression was decreased in glioma. SMAD4 mRNA and protein levels were both lower in glioma compared to control on real-time PCR and Western blot analysis (both P < 0.001). In addition, its expression levels decrease from grade I to grade IV glioma according to the results of real-time PCR, immunohistochemistry analysis and Western blot. Moreover, the survival rate of SMAD4-positive patients was higher than that of SMAD4-negative patients. We further confirmed that the loss of SMAD4 was a significant and independent prognostic indicator in glioma by multivariate analysis.</p> <p>Conclusions</p> <p>Our data provides convincing evidence for the first time that the reduced expression of SMAD4 at gene and protein levels is correlated with poor outcome in patients with glioma. SMAD4 may play an inhibitive role during the development of glioma and may be a potential prognosis predictor of glioma.</p

Phage display mediated immuno-PCR

Immuno-PCR (IPCR) is a powerful detection technology in immunological study and clinical diagnosis due to its ultrasensitivity. Here we introduce a new strategy termed phage display mediated immuno-PCR (PD-IPCR). Instead of utilization of monoclonal antibody (mAb) and chemically bond DNA that required in the conventional IPCR, a recombinant phage particle is applied as a ready reagent for IPCR experiment. The surface displayed single chain variable fragment (scFv) and phage DNA themselves can directly serve as detection antibody and PCR template, respectively. The aim of the design is to overcome shortcoming of low detection sensitivity of scFv so as to largely facilitate the real application of scFv in immunoassay. The idea has been demonstrated by applying hantaan virus nucleocapsid protein (NP) and prion protein (PrP) as detection targets in three experimental protocols (indirect, sandwich and real-time PD-IPCR assays). The detection sensitivity was increased 1000- to 10 000-folds compared with conventional enzyme-linked immunosorbent assays (ELISAs). This proof-of-concept study may serve as a new model to develop an easy to operate, low cost and ultrasensitive immunoassay method for broad applications