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

Distinct Tumor Microenvironment at Tumor Edge as a Result of Astrocyte Activation Is Associated With Therapeutic Resistance for Brain Tumor

Tumor vasculatures and hypoxia are critical tumor micro-environmental factors associated with tumor response to the therapy and heterogeneous in both time- and location-dependent manner. Using a murine orthotopic anaplastic astrocytoma model, ALTS1C1, this study showed that brain tumor edge had a very unique microenvironment, having higher microvascular density (MVD) and better vessel function than the tumor core, but on the other hand was also positive for hypoxia markers, such as pimonidazole (PIMO), hypoxia inducible factor-1α (HIF-1α), and carbonic anhydrase IV (CAIX). The hypoxia at tumor edge was transient, named as peripheral hypoxia, and caused by different mechanisms from the chronic hypoxia in tumor core. The correlation of CAIX staining with astrocyte activation marker, glial fibrillary acid protein (GFAP), at the tumor edge indicated the involvement of astrocyte activation on the development of peripheral hypoxia. Peripheral hypoxia was a specific trait of orthotopic brain tumors at tumor edge, regardless of tumor origin. The hypoxic cells were resistant to the therapy, regardless of their location. Surviving cells, particularly those at the hypoxic region of tumor edge, are likely the cause of tumor recurrence after the therapy. New therapeutic platform that targets cells in tumor edge is likely to achieve better treatment outcomes

Effect of omega-3 fatty acid supplementation on cancer incidence, non-vascular death, and total mortality: a meta-analysis of randomized controlled trials

BACKGROUND: Omega-3 fatty acids are known to prevent cardiac death. However, previous observational studies have suggested that omega-3 fatty acids are associated with cancer risk in adults. We conducted a meta-analysis based on randomized controlled trials to evaluate the effect of omega-3 fatty acids on the risk of cancer incidence, nonvascular death, and total mortality. METHODS: In February 2013, we performed electronic searches in PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials on cancer incidence, nonvascular death, and total mortality. Relative risk (RR) was used to measure the effect of omega-3 fatty acid supplementation on the risk of cancer incidence, nonvascular death, and total mortality using a random-effect model. The analysis was further stratified by factors that could affect the treatment effects. RESULTS: Of the 8,746 identified articles, we included 19 trials reporting data on 68,954 individuals. These studies reported 1,039 events of cancer, 2,439 events of nonvascular death, and 7,025 events of total mortality. Omega-3 fatty acid supplementation had no effect on cancer incidence (RR, 1.10; 95% CI: 0.97–1.24; P = 0.12), nonvascular death (RR, 1.00; 95% CI: 0.93–1.08; P = 1.00), or total mortality (RR, 0.95; 95% CI: 0.88–1.03; P = 0.24) when compared to a placebo. Subgroup analysis indicated that omega-3 fatty acid supplementation was associated with a reduction in total mortality risk if the proportion of men in the study population was more than 80%, or participants received alpha-linolenic acid. CONCLUSIONS: Omega-3 fatty acid supplementation does not have an effect on cancer incidence, nonvascular death, or total mortality

Sclerotherapy for the recurrent granulomatous epulis with pingyangmycin

Relapse of granulomatous epulis is common after surgery because of local irritations, hormonal level in vivo, or incomplete resection. Currently, if recurrence occurs, then extraction of the teeth adjacent to the lesion is commonly performed, which may influence the aesthetics or masticatory function. Thus, a more effective and less aggressive treatment method is urgently demanded, particularly for the recurring lesion. This study investigated the effects of the intralesional pingyangmycin (PYM) injections for the recurrent granulomatous epulis and assessed the complications. A total of 16 patients with recurrent granulomatous epulis underwent intralesional PYM injections, between July 2010 and June 2014. The effects and complications of the treatment were retrospectively reviewed. The total number of injections performed was 48 (for all patients). The median number of injections per patient was three (range, two to four). All cases completely recovered with no recurrence and resorption of the alveolar bone after a follow-up of more than 12 months. The complications included slight bleeding, local swelling and pain following injection. All these symptoms resolved 7 to 10 days after the injection. In summary, intralesional PYM injections may be a preferred option for recurring granulomatous epulis

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

DIGAP - a Database of Improved Gene Annotation for Phytopathogens

<p>Abstract</p> <p>Background</p> <p>Bacterial plant pathogens are very harmful to their host plants, which can cause devastating agricultural losses in the world. With the development of microbial genome sequencing, many strains of phytopathogens have been sequenced. However, some misannotations exist in these phytopathogen genomes. Our objective is to improve these annotations and store them in a central database DIGAP.</p> <p>Description</p> <p>DIGAP includes the following improved information on phytopathogen genomes. (i) All the 'hypothetical proteins' were checked, and non-coding ORFs recognized by the Z curve method were removed. (ii) The translation initiation sites (TISs) of 20% ~ 25% of all the protein-coding genes have been corrected based on the NCBI RefSeq, ProTISA database and an <it>ab initio </it>program, GS-Finder. (iii) Potential functions of about 10% 'hypothetical proteins' have been predicted using sequence alignment tools. (iv) Two theoretical gene expression indices, the codon adaptation index (CAI) and the <it>E</it>(<it>g</it>) index, were calculated to predict the gene expression levels. (v) Potential agricultural bactericide targets and their homology-modeled 3D structures are provided in the database, which is of significance for agricultural antibiotic discovery.</p> <p>Conclusion</p> <p>The results in DIGAP provide useful information for understanding the pathogenetic mechanisms of phytopathogens and for finding agricultural bactericides. DIGAP is freely available at <url>http://ibi.hzau.edu.cn/digap/</url>.</p

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