Antiviral bioactivity of resveratrol against Zika virus infection in human retinal pigment epithelial cells

Resveratrol (RES) is a polyphenol with increasing interest for its inhibitory effects on a wide variety of viruses. Zika virus (ZIKV) is an arbovirus which causes a broad spectrum of ophthalmological manifestations in humans. Currently there is no certified therapy or vaccine to treat it, thus it has become a major global health threat. Retinal pigment epithelium (RPE) is highly permissive and susceptible to ZIKV. This work explored the protective effects of RES on ZIKV-infected human RPE cells. RES treatment resulted in a significant reduction of infectious viral particles in infected male ARPE-19 and female hTERT-RPE1 cells. This protection was positively influenced by the action of RES on mitochondrial dynamics. Also, docking studies predicted that RES has a high affinity for two enzymes of the rate-limiting steps of pyrimidine and purine biosynthesis and viral polymerase. This evidence suggests that RES might be a potential antiviral agent to treat ZIKV-induced ocular abnormalities.

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Metabolism of the anticancer agent 1-(4-acetylphenyl)-3,3-dimethyltriazene

High pressure liquid chromatography was used in combination with mass spectrometry to confirm that the main products of in vitro metabolism of 1-(4-acetylphenyl)-3,3-dimethyltriazene are 1-(4-acetylphenyl-3-methyltriazene and 4-aminoacetophenone. In addition a novel metabolite, 1-[4-(1-hydroxyethyl)-phenyl]-3,3-dimethyltriazene, possessing antitumour activity similar to the parent drug, was identified.     

Cytoprotective Effect of Ferritin H in Renal Ischemia Reperfusion Injury

Oxidative stress is a major contributor to kidney injury following ischemia reperfusion. Ferritin, a highly conserved iron-binding protein, is a key protein in the maintenance of cellular iron homeostasis and protection from oxidative stress. Ferritin mitigates oxidant stress by sequestering iron and preventing its participation in reactions that generate reactive oxygen species. Ferritin is composed of two subunit types, ferritin H and ferritin L. Using an in vivo model that enables conditional tissue-specific doxycycline-inducible expression of ferritin H in the mouse kidney, we tested the hypothesis that an increased level of H-rich ferritin is renoprotective in ischemic acute renal failure. Prior to induction of ischemia, doxycycline increased ferritin H in the kidneys of the transgenic mice nearly 6.5-fold. Following reperfusion for 24 hours, induction of neutrophil gelatinous-associated lipocalin (NGAL, a urine marker of renal dysfunction) was reduced in the ferritin H overexpressers compared to controls. Histopathologic examination following ischemia reperfusion revealed that ferritin H overexpression increased intact nuclei in renal tubules, reduced the frequency of tubular profiles with luminal cast materials, and reduced activated caspase-3 in the kidney. In addition, generation of 4-hydroxy 2-nonenal protein adducts, a measurement of oxidant stress, was decreased in ischemia-reperfused kidneys of ferritin H overexpressers. These studies demonstrate that ferritin H can inhibit apoptotic cell death, enhance tubular epithelial viability, and preserve renal function by limiting oxidative stress following ischemia reperfusion injury.     

Characterization of the insulin and insulin-like growth factor receptors and responsitivity of a fibroblast/adipocyte cell line before and after differentiation

TA1 cells, like 3T3-L1 cells, undergo a differentiation process in vitro from a fibroblast to an adipocyte phenotype. The TA1 pre-adipocytes were found to have low numbers of insulin receptors but high numbers of receptors for insulin-like growth factors (IGF) I and II. Also, the pre-adipocytes were more responsive to IGF than insulin as measured by either stimulation of glucose or amino acid uptake. After differentiation, the adipocytes had higher numbers of insulin receptors and a better responsitivity to insulin than to IGF-I. These results indicate that insulin-like growth factors are the primary regulators of the pre-adipocytes whereas insulin regulates the adipocytes.     

Stimulation of human platelets with concanavalin A involves phospholipase C activation.

In response to concanavalin A, cytoplasmic calcium movement was observed in human platelets, both in the presence of 1 mM Ca2+ or 1 mM EGTA in the medium. Concanavalin A also caused the activation of inositide turnover and the production of inositol phosphates, suggesting that activation of phospholipase C occurs. The mechanism by which concanavalin A stimulates phospholipase C does not depend on GTP-binding transducers, because it was not inhibited by GDP beta S, while experiments performed in the presence of cytochalasin B suggested a role for membrane glycoprotein IIb-IIIa-cytoskeleton interaction in this process. Ca(2+)-proteases and Na+/H+ antiport also seemed to be related to concanavalin A-induced phospholipase C activation, as suggested by experiments performed in the presence of leupeptin and amiloride.     

DNA methylation of embryogenic carrot cell cultures and its variations as caused by mutation,differentiation, hormones and hypomethylating drugs

Summary The level of auxin - both natural and synthetic — in the medium has a strong effect on the level of 5-methyl-cytosine in the DNA of carrot cells in culture. This level may vary from approximately 15% to 70% of total cytosine without apparent effects on growth rate and cell morphology. No effect was seen with cytokinin. During somatic embryogenesis, in the absence of hormones, variations were seen in the level of methylation according to a characteristic pattern. If hypomethylation is induced with drugs such as azacytidine, ethionine or ethoxy-carbonyl-pyrimidine, embryogenesis is immediately blocked. A mutant was isolated which is resistant to the action of hypomethylating drugs. It shows variations in the methylation pattern and variations in indole-acetic acid metabolism. In addition its regeneration is often associated with the production of tumors.Deceased     

Effect of GPIIb-IIIa complex ligands on calcium ion movement and cytoskeleton organization in activated platelets

We studied the influence of the occupancy of the fibrinogen receptor (GP IIb-IIIa complex) on two early aspects of agonist induced platelet activation: the increase of the intracellular Ca2+ concentration and the cytoskeleton reorganization. A monoclonal antibody, a peptide containing the RGD sequence and fibrinogen purified from human plasma were used as GP IIb-IIIa ligands. The obtained results demonstrated that fibrinogen receptor occupancy inhibits Ca2+ movement and cytoskeleton reorganization caused by low thrombin concentration and ADP.     

A New Basal Subfamily of mariner Elements in Ceratitis rosa and Other Tephritid Flies

Several copies of highly related transposable elements, Crmar2, Almar1, and Asmar1, are described from the genomes of Ceratitis rosa, Anastrepha ludens, and A. suspensa, respectively. One copy from C. rosa, Crmar2.5, contains a full-length, uninterrupted ORF. All the other copies, from the three species contain a long deletion within the putative ORF. The consensus Crmar2 element has features typical of the mariner/Tc1 superfamily of transposable elements. In particular, the Crmar2 consensus encodes a D,D41D motif, a variant of the D,D34D catalytic domain of mariner elements. Phylogenetic analysis of the relationships of these three elements and other members of the mariner/Tc1 superfamily, based on their encoded amino acid sequences, suggests that they form a new basal subfamily of mariner elements, the rosa subfamily. BLAST analyses identified sequences from other diptera, including Drosophila melanogaster, which appear to be members of the rosa subfamily of mariner elements. Analyses of their molecular evolution suggests that Crmar2 entered the genome of C. rosa in the recent past, a consequence of horizontal transfer.