Effects of flavonoids on tongue squamous cell carcinoma

Squamous cell carcinoma (SCC) of the tongue is associated with tobacco use, alcohol abuse, and human papillomavirus (HPV) infections. While clinical outcomes have recently improved for HPV‐positive patients in general, 50% of patients suffering from tongue cancer die within 5 years of being diagnosed. Flavonoids are secondary plant metabolites with a wide range of biological activities including antioxidant, anti‐inflammatory, and anticancer activities. Flavonoids have generated high interest as therapeutic agents owing to their low toxicity and their effects on a large variety of cancer cell types. In this literature review, we evaluate the actions of flavonoids on SCC of the tongue demonstrated in both in vivo and in vitro models.     

Enthalpie and Entropie Contributions in the Transesterification of Sucrose: Computational Study of Lipases and Subtilisin

Abstract

Transesterification of sucrose with fatty acids catalyzed by subtilisin Carlsberg occurs with regioselectivity that is different from that in lipases. Thermomyces lanuginosus lipase (TlL) and Candida antarctica lipase B (CALB) catalyze synthesis at positions 6 and 6′, with differing abilities, while subtilisin catalysis leads to the l′-acylated sucrose. The catalytic machinery in lipases is approximately mirrored in subtilisins but different pocket morphologies including size, shape, and rearrangement of the catalytic elements underlies the differing regioselectivities. The thermodynamic consequences of these differences on the above reactions have been explored systematically using computational methods, determining the free energies of interaction of the putative transition-state adducts. Analysis of the conformers with the lowest transition state energies (protein-ligand interactions and vibrational entropy contributions) indicates that enthalpic factors control specificities in lipases while entropic factors are more important in subtilisin.     

Atmospheric pollen in Santiago,Chile

In the city of Santiago (33°27'S70°38'W), Chile, an atmospheric pollen was monitored for three years using a volumetric Hirst-type pollen trap. The aims of the study were: to assess the pollen types present in the atmosphere, their actual concentrations and dynamics (means and maxima); to establish the pollen calendar for Santiago; and to analyze the aerobiologic characteristics distinguishing introduced and native taxa. Results show that atmospheric pollen mainly originates from the following taxa: Platanus , Poaceae, Acer , Cupressus , Chenopodiaceae, Urticaceae, Morus , Plantago and Oleaceae. For the most frequent pollen types graphs of their atmospheric presence constructed and a table with relevant yearly data for the three studied (July-June) is presented. It is concluded, that the airborne pollen is originating mainly from introduced taxa, many of which are considered allergenic. Native taxa showed no high concentrations. The highest aiborne pollen concentrations where observed in September, however, atmospheric pollen thought to be capable of causing pollinosis, where present during the whole year. The highest pollen concentrations are mostly from trees.     

Use of Psoralen Monoadducts to Compare The Structure of 16S rRNA in Active and Inactive 30S Ribosomal Subunits

Abstract

E. coli 30S ribosomes in the inactive conformation were irradiated at 390 nm in the presence of 4′ -aminomethyl-4,5′,8-trimethylpsoralen (AMT). This produces monoadducts in which AMT is attached to only one strand of an RNA duplex region. After unbound AMT was removed, some ribosomes were activated and then subjected to 360 nm irradiation; others were reirradiated without activation. Electron microscopic examination of 16S rRNA extracted from these two samples showed covalent rRNA loops indicative of rRNA crosslinks. The general pattern of loops closely matched that seen previously after direct psoralen crosslinking of 30S particles. However, the frequency of occurrence of one major class of loops formed by crosslinks between residues near position 500 and the 3′ end was substantially lower for the activated samples, implying that the structure of the 16S rRNA in active and inactive 30S particles is different.     

Molecular modeling study on potent and selective adenosine A(3) receptor agonists

Adenosine A(3) receptor (A(3)AR) is involved in a variety of key physio-pathological processes and its agonists are potential therapeutic agents for the treatment of rheumatoid arthritis, dry eye disorders, asthma, as anti-inflammatory agents, and in cancer therapy. Recently reported MECA (5'-N-methylcarboxamidoadenosine) derivatives bearing a methyl group in N(6)-position and an arylethynyl substituent in 2-position demonstrated to possess sub-nanomolar affinity and remarkable selectivity for the human A(3)AR, behaving as full agonists of this receptor. In this study, we made an attempt to get a rationalization of the high affinities and selectivities of these molecules for the human A(3)AR, by using adenosine receptor (AR) structural models based on the A(2A)AR crystal structure and molecular docking analysis. Post-docking analysis allowed to evaluate the ability of modeling tools in predicting AA(3)R affinity and in providing interpretation of compound substituents effect on the A(3)AR affinity and selectivity.     

The phylogeny of Gaura (Onagraceae) based on ITS, ETS, and trnL-F sequence data

Gaura (Onagraceae: Onagreae) is a small North American genus of 21 species consisting mostly of night-blooming, moth-pollinated annuals and perennials. The current infrageneric classification based on differences in habit, floral symmetry, and fruit morphology recognizes eight sections within the genus. We examine the phylogenetic relationships of all 21 species of Gaura using DNA sequence data from the internal transcribed spacer region (ITS), the external transcribed spacer region (ETS), and the plastid trnL-F region. Combined analysis of these regions indicate Gaura is monophyletic only if it includes Stenosiphon, a monotypic genus comprised of S. linifolius. Within Gaura, our studies indicate that sections Gauridium, Schizocarya, Campogaura, Stipogaura, Xenogaura, and Gaura are monophyletic, but sections Xerogaura and Pterogaura are not and should be reevaluated. In addition, molecular data provide support for the hypothesis that G. sinuata and G. drummondii arose via interspecific hybridization followed by genome doubling; their influence on phylogenetic reconstruction is discussed.     

Accumulation of symmetric dimethylarginine in hepatorenal syndrome

In patients with cirrhosis, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and possibly symmetric dimethylarginine (SDMA) have been linked to the severity of the disease. We investigated whether plasma levels of dimethylarginines and NO are elevated in patients with hepatorenal syndrome (HRS), compared with patients with cirrhosis without renal failure (no-HRS). Plasma levels of NO, ADMA, SDMA, and l-arginine were measured in 11 patients with HRS, seven patients with no-HRS, and six healthy volunteers. SDMA concentration in HRS was higher than in no-HRS and healthy subjects (1.47 +/- 0.25 vs. 0.38 +/- 0.06 and 0.29 +/- 0.04 microM, respectively; P < 0.05). ADMA and NOx concentrations were higher in HRS and no-HRS patients than in healthy subjects (ADMA, 1.20 +/- 0.26, 1.11 +/- 0.1, and 0.53 +/- 0.06 microM, respectively; P < 0.05; NOx, 94 +/- 9.1, 95.5 +/- 9.54, and 37.67 +/- 4.62 microM, respectively; P < 0.05). In patients with HRS there was a positive correlation between serum creatinine and plasma SDMA (r2 =0.765, P < 0.001) but not between serum creatinine and ADMA or NOx. The results suggest that renal dysfunction is a main determinant of elevated SDMA concentration in HRS. Accumulation of ADMA as a result of impaired hepatic removal may be the causative factor initiating renal vasoconstriction and SDMA retention in the kidney.     

Lung retinol storing cells synthesize and secrete retinoic acid,an inducer of alveolus formation

Retinoids play a key role in the formation of pulmonary alveoli. Lipid interstitial cells (LICs) of the alveolar wall store retinol and are concentrated at sites of alveolus formation, suggesting they are an endogenous source of retinoids for alveolus formation. We show in cultured rat lung cells that LICs synthesize and secrete all-trans retinoic acid (ATRA); its secretion is halved by dexamethasone, an inhibitor of alveolus formation. In a second alveolar wall cell, the pulmonary microvascular endothelial cell (PMVC), ATRA increases expression of the mRNA of cellular retinol binding protein-I (CRBP-I), a protein involved in ATRA synthesis. Serum-free, exogenous ATRA-free medium conditioned by LICs rich in retinol storage granules caused a 10-fold greater increase of CRBP-I mRNA in PMVCs than media conditioned by LICs with few retinol storage granules. This action of medium conditioned by retinol storage granule-rich LICs is decreased by a retinoic acid receptor pan-antagonist and by a retinoid X receptor pan-antagonist, suggesting the responsible molecule(s) is a retinoid and that retinoid signaling occurs in a paracrine fashion.     

Differential Targeting of SLC30A10/ZnT10 Heterodimers to Endolysosomal Compartments Modulates EGF‐Induced MEK/ERK1/2 Activity

The solute carrier 30A (SLC30A) family of zinc exporters transports zinc into the lumen of intracellular organelles in order to prevent zinc toxicity. We reported that formation of tyrosine dimers is required for ZnT3 (zinc transporter 3) zinc transport activity and targeting to synaptic‐like microvesicles (SLMVs) in PC12 cells and the formation of ZnT3/ZnT10 heterodimers. Here, we focused on ZnT10 to determine the role of heterodimerization in the sorting of ZnTs in the endolysosomal pathway. Using cell fractionation, immunoprecipitation and immunofluorescence approaches, we found that ZnT10 resides in transferrin receptor and Rab5‐positive endosomes and forms covalent heterodimers and oligomers with ZnT2, ZnT3 and ZnT4. The interaction of ZnT10 with ZnT3, mediated by dityrosine bonds, was unable to target ZnT10 into SLMVs in vitro or into synaptic vesicles isolated from mouse brain in vivo. However, ZnT3/ZnT10 heterodimers regulate epidermal growth factor receptor (EGF‐R) signaling by increasing the phosphorylation of mitogen‐activated protein kinase kinase (MEK) and extracellular signal‐regulated kinase (ERK1/2), but not EGF‐R, C‐Raf or Akt phosphorylation in response to EGF. Further, mutation of tyrosine 4 in ZnT10 reduced ZnT3/ZnT10 dityrosine‐mediated heterodimerization and zinc transport, as well as MEK and ERK1/2 phosphorylation, which were also reduced by the zinc chelator TPEN. Phosphorylation of these kinases is likely to occur in the cytosol as no differences in phosphorylation were observed in membrane fractions of control and ZnT3/ZnT10‐expressing cells. We propose that ZnT10 plays a role in signal transduction, which is mediated by homo and heterodimerization with other ZnTs.