Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model

<p>Abstract</p> <p>Background</p> <p>To determine whether oral administration of geranylgeranylacetone (GGA), a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP) 70, protects against drug-induced lung injury/fibrosis <it>in vivo</it>.</p> <p>Methods</p> <p>We used a bleomycin (BLM)-induced lung fibrosis model in which mice were treated with oral 600 mg/kg of GGA before and after BLM administration. Inflammation and fibrosis were evaluated by histological scoring, hydroxyproline content in the lung and inflammatory cell count, and quantification by ELISA of macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid. Apoptosis was evaluated by the TUNEL method. The induction of HSP70 in the lung was examined with western blot analysis and its localization was determined by immunohistochemistry.</p> <p>Results</p> <p>We confirmed the presence of inflammation and fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral administration of GGA. GGA prevented apoptosis of cellular constituents of lung tissue, such as epithelial cells, most likely related to the <it>de novo </it>induction of HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs, associated with the findings of suppression of both production of MIP-2 and inflammatory cell accumulation in the injured lung, compared with vehicle-treated mice.</p> <p>Conclusion</p> <p>GGA had a protective effect on drug-induced lung injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate, which are indispensable for the treatment of rheumatoid arthritis, often cause interstitial lung diseases, an adverse event that currently cannot be prevented. Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in the future.</p

Rewriting DNA Methylation Signatures at Will:The Curable Genome Within Reach?

DNA methyltransferases are important enzymes in a broad range of organisms. Dysfunction of DNA methyltransferases in humans leads to many severe diseases, including cancer. This book focuses on the biochemical properties of these enzymes, describing their structures and mechanisms in bacteria, humans and other species, including plants, and also explains the biological processes of reading of DNA methylation and DNA demethylation. It covers many emerging aspects of the biological roles of DNA methylation functioning as an essential epigenetic mark and describes the role of DNA methylation in diseases. Moreover, the book explains modern technologies, like targeted rewriting of DNA methylation by designed DNA methyltransferases, as well as technological applications of DNA methyltransferases in DNA labelling. Finally, the book summarizes recent methods for the analysis of DNA methylation in human DNA. Overall, this book represents a comprehensive state-of-the-art- work and is a must-have for advanced researchers in the field of DNA methylation and epigenetics

A Tool For Explaining The Differences on Renneting Characteristics of Milks From Different Origins: The Surface Hydrophobicity Approach

The differences between renneting characteristics of raw milk samples from different origins (bovine, ovine, caprine, buffalo) were investigated by protein surface hydrophobicity approach. 8-Anilinonaphthalene-1-sulfonic acid (ANS) binding method was used to evaluate surface hydrophobicity of raw milk samples and rennet precipitates. The following surface hydrophobicity parameters were calculated: number of surface hydrophobic sites (F (max)), dissociation constant of the fluorescent ANS-protein complex (K (d)), binding affinity of ANS to protein surface (1/K (d)), the average tightness of binding of ANS to the protein (F (max)/K (d)), turnover number (k (cat)), and protein surface hydrophobicity index (PSHI). The number of hydrophobic sites on the protein surface was found to be highest in cow milk, whereas ovine milk samples had the lowest number of hydrophobic sites and binding affinity to ANS. Protein content was not found directly related to the number of surface hydrophobic sites. The binding affinity of the proteins to ANS was greater in buffalo milk. PSHI was found to be the highest for bovine milk and the lowest for ovine milk. Renneting period was interpreted in two phases (enzymatic phase and flocculation phase) for each origin via ANS partition curves of rennet precipitates. Same trends between bovine-ovine and caprine-buffalo milks were observed during renneting. Buffalo milk completed both of two phases and total renneting period significantly earlier than the milks from the other origins. The hydrophobic parameters of proteins were found to play a key role on coagulation properties.Wo

Chelating, antioxidant and antiproliferative activity of Vicia sativa polyphenol extracts

The metal chelating activity, antioxidant properties, and the effect on cell growth of a polyphenol extract from Vicia sativa have been investigated, and compared to those of soybean. The extracts from V. sativa seeds contained three and five times more polyphenols and flavonoids than soybean, respectively. The soybean polyphenol extracts showed higher copper and iron chelating activity than those from V. sativa, although polyphenols from V. sativa were more effective in preventing β-carotene oxidation and showed higher reducing power and scavenging activity than soybean polyphenols. In addition, V. sativa polyphenols were toxic to THP-1 leukemic cells, as opposed to polyphenols extracted from soybean that did not show any antiproliferative activity at similar concentrations. In conclusion, V. sativa polyphenol extracts show promising antioxidant and antiproliferative activities that may be of interest from a functional point of view and for the revalorization of this ancient crop.This work was supported by grant AGR-711 from Junta de Andalucía (Spain).Peer reviewe