Pegylated interferon alfa for chronic hepatitis B: systematic review and meta-analysis.

Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used for chronic hepatitis B (CHB) treatment, but are associated with adverse effects and viral resistance. Here we performed a systematic review and meta-analysis evaluating all studies of pegylated interferon alfa (PEG-IFNα) treatment in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB. We searched electronic databases--PubMed, EMBASE, Cochrane Library and LILACS--for randomized controlled trials evaluating PEG-IFNα therapy between 1999 and September 2014. Virological response was the primary outcome. We identified 14 studies involving 2829 patients. Our analysis revealed that PEG-IFNα + lamivudine combination therapy produced better virological and biochemical responses than PEG-IFNα monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment. PEG-IFNα + adefovir dipivoxil achieved better seroconversion rate than PEG-IFNα in HBeAg-positive patients at the end of treatment. The present findings demonstrated a beneficial response rate following PEG-IFNα combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB. Further trials are needed to investigate simultaneous and sequential therapy strategies.

Antimicrobial activity of phenolic compounds identified in wild mushrooms, SAR analysis and docking studies.

AIM AND METHODS: Although the antimicrobial activity of extracts from several mushroom species has been reported, studies with the individual compounds present in that extracts are scarce. Herein, the antimicrobial activity of different phenolic compounds identified and quantified in mushroom species from all over the world was evaluated. Furthermore, a structure-activity relationship (SAR) analysis and molecular docking studies were performed, in order to provide insights into the mechanism of action of potential antimicrobial drugs for resistant micro-organisms. RESULTS: 2,4-Dihydroxybenzoic and protocatechuic acids were the phenolic compounds with higher activity against the majority of Gram-negative and Gram-positive bacteria. Furthermore, phenolic compounds inhibited more MRSA than methicillin-susceptible Staphylococcus aureus. MRSA was inhibited by 2,4-dihydroxybenzoic, vanillic, syringic (MICs = 0.5 mg ml(-1) ) and p-coumaric (MIC = 1 mg ml(-1) ) acids, while these compounds at the same concentrations had no inhibitory effects against methicillin-susceptible Staph. aureus. CONCLUSIONS: The presence of carboxylic acid (COOH), two hydroxyl (OH) groups in para and ortho positions of the benzene ring and also a methoxyl (OCH3 ) group in the meta position seems to be important for anti-MRSA activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Phenolic compounds could be used as antimicrobial agents, namely against some micro-organisms resistant to commercial antibiotics.

Using molecular docking to investigate the anti-breast cancer activity of low molecular weight compounds present on wild mushrooms.

Mushrooms represent an unlimited source of compounds with anti-tumour and immunostimulating properties, and their intake has been shown to reduce the risk of breast cancer. A large number of low molecular weight (LMW) compounds present in mushrooms have been identified, including phenolic acids, flavonoids, tocopherols, carotenoids, sugars and fatty acids. In order to evaluate which wild mushroom LMW compounds may be involved in anti-breast cancer activity we selected a representative dataset of 43 LMW compounds and performed molecular docking against three known protein targets involved in breast cancer (aromatase, estrone sulfatase and 17ß-HSD-1) using AutoDock4 as docking software. The estimated inhibition constants for all LMW compounds were determined, and the potential structure-activity relationships for the compounds with the best estimated inhibition constants are discussed for each compound family. 4-O-caffeoylquinic, naringin and lycopene stand out as the top-ranked potential inhibitors for aromatase, estrone sulfatase and 17ß-HSD1, respectively, and the 3-D docked conformations for these compounds are discussed in detail. This information provides several interesting starting points for further development of aromatase, estrone sulfatase and 17ß-HSD1 inhibitors.

ChemT, an open-source software for building template-based chemical libraries.

In computational chemistry, vast quantities of compounds are generated, and there is a need for cheminformatic tools to efficiently build chemical compound libraries. Several software tools for drawing and editing compound structures are available, but they lack options for automatic generation of chemical libraries. We have implemented ChemT, an easy-to-use open-source software tool that automates the process of preparing custom-made template-based chemical libraries. ChemT automatically generates three-dimensional chemical libraries by inputting a chemical template and the functional groups of interest. The graphical user interface of ChemT is self-explanatory, and a complete tutorial is provided. Several file formats are accepted by ChemT, and it is possible to filter the generated compounds according to different physicochemical properties. The compounds can be subject to force field minimization, and the resulting three-dimensional structures recorded on commonly used file formats. ChemT may be a valuable tool for investigators interested in using in silico virtual screening tools, such as quantitative structure-activity relationship modelling or molecular docking, in order to prioritize compounds for further chemical synthesis. To demonstrate the usefulness of ChemT, we describe an example based on a thieno[3,2-b]pyridine template. ChemT is available free of charge from our website at http://www.esa.ipb.pt/~ruiabreu/chemt .

A QCAR model for predicting antioxidant activity of wild mushrooms.

Wild mushrooms have been described as sources of natural antioxidants, particularly phenolic compounds. However, many other compounds present in wild mushrooms can also act as antioxidants (reducers), so whole extracts from a wide range of species need to be examined. To gain further knowledge in this area, the relationship between the antioxidant potential (scavenging effect and reducing power) and chemical composition of twenty three samples from seventeen Portuguese wild mushroom species was investigated. A wide range of analytical parameters reported by our research group (including ash, carbohydrates, proteins, fat, monounsaturated fatty acids, polyunsaturated fatty acids, saturated fatty acids, phenolics, flavonoids, ascorbic acid and beta-carotene) were studied and the data were analysed by partial least squares (PLS) regression analysis to allow correlation of all the parameters. Antioxidant activity correlated well with phenolic and flavonoid contents. A QCAR (Quantitative Composition-Activity Relationships) model was constructed, using the PLS method, and its robustness and predictability were verified by internal and external cross-validation methods. Finally, this model proved to be a useful tool in the prediction of mushrooms' reducing power.

Effects of carvedilol and its analog BM-910228 on mitochondrial function and oxidative stress.

The antioxidant effects of carvedilol and its analog BM-910228 (also known as SB 211475) were studied in rat liver mitochondria as well as their action on mitochondrial bioenergetics. Carvedilol and BM-910228 inhibited ADP/Fe(2+)-initiated lipid peroxidation (measured in mitochondrial membranes as thiobarbituric acid reactive substances and oxygen consumption) with IC(50) values of 10.9 and 0. 33 microM, respectively. Under the same conditions, the IC(50) value for Trolox C was 18.8 microM. At the same concentration range showing antioxidant activity both compounds prevent the collapse of transmembranar electric potential induced by ADP/Fe(2+) on respiring mitochondria. Furthermore, both carvedilol and BM-910228 do not display toxic effects on mitochondria up to the concentration showing maximal antioxidant effects ( approximately 40 microM for carvedilol and approximately 1 microM for BM-910228). At higher concentrations of carvedilol (>40 microM), however, the phosphorylation efficiency of mitochondria is depressed as deduced from a decrease in respiratory control and in the ADP/oxygen ratio. The Brand approach was used to assess the effects of carvedilol on oxidative phosphorylation. We found that carvedilol stimulated membrane proton leak and inhibited substrate oxidation, but had no measurable effect on phosphorylation reactions. Because carvedilol exerts its antioxidant properties for nontoxic concentrations, its therapeutic interest is reinforced because it may potentially prevent mitochondrial dysfunctions associated to cell death in several pathophysiological states where excessive production of reactive oxygen species by mitochondria is well documented (e.g., ischemia/reperfusion). Additionally, its hydroxylated analog BM-910228 with notable superior antioxidant activity may significantly contribute to the known therapeutic effects of carvedilol.