The oxidative damage to the human telomere: effects of 5-hydroxymethyl-2'-deoxyuridine on telomeric G-quadruplex structures

As part of the genome, human telomeric regions can be damaged by the chemically reactive molecules responsible for oxidative DNA damage. Considering that G-quadruplex structures have been proven to occur in human telomere regions, several studies have been devoted to investigating the effect of oxidation products on the properties of these structures. However only investigations concerning the presence in G-quadruplexes of the main oxidation products of deoxyguanosine and deoxyadenosine have appeared in the literature. Here, we investigated the effects of 5-hydroxymethyl-2’-deoxyuridine (5-hmdU), one of the main oxidation products of T, on the physical–chemical properties of the G-quadruplex structures formed by two human telomeric sequences. Collected calorimetric, circular dichroism and electrophoretic data suggest that, in contrast to most of the results on other damage, the replacement of a T with a 5-hmdU results in only negligible effects on structural stability. Reported results and other data from literature suggest a possible protecting effect of the loop residues on the other parts of the G-quadruplexes

Childhood overweight-obesity and periodontal diseases: is there a real correlation?

Objective. The association between obesity and periodontitis has been extensively investigated in adults but not in young people. The aim of this study was to examine the association between overweight-obesity and periodontal disease in pediatric subjects. Methods. Controlled cross-sectional study involving 100 school children of both gender (50 M and 50 F) between 7 and 12 years of age (mean age 9,19 +/- 1,57). Two groups were formed based on Body Mass Index value: test group with BMI >= 25 Kg/m(2) and control group with BMI <= 24 Kg/m(2). Diet intake and oral hygiene habits were recorded by a specific questionnaire and the periodontal clinical parameters were evaluated. Results. The periodontal examination in the control group revealed a full-mouth plaque score (FMPS) value equal to 21.86% against 50.08% in the group of patients overweight/obese; the full-mouth bleeding score (FMBS) in the control group amounted to 12.7% against 26.24% of test group. No patient in either group included in the study presented a probing pocket depth (PPD) >= 3, so a significant difference regarding this value was not found. Regarding the frequency and quantity of food consumption, the number of obese patients who did not follow a balanced diet largely exceeded the number of normal-weight patients (70 versus 20%). Conclusions. These results focus the attention on the negative impact of obesity on gingival health in young subjects, probably due to a combination of metabolic and inflammatory profiles and the result of a careless attitude towards prevention diseases of the oral cavit

Exploring the binding of d(GGGT)4 to the HIV-1 integrase: An approach to investigate G-quadruplex aptamer/target protein interactions.

The aptamer d(GGGT)4 (T30923 or T30695) forms a 5'-5' dimer of two stacked parallel G-quadruplexes, each characterized by three G-tetrads and three single-thymidine reversed-chain loops. This aptamer has been reported to exhibit anti-HIV activity by targeting the HIV integrase, a viral enzyme responsible for the integration of viral DNA into the host-cell genome. However, information concerning the aptamer/ target interaction is still rather limited. In this communication we report microscale thermophoresis investigations on the interaction between the HIV-1 integrase and d(GGGT)4 aptamer analogues containing abasic sites singly replacing thymidines in the original sequence. This approach has allowed the identification of which part of the aptamer G-quadruplex structure is mainly involved in the interaction with the protei

Numerical approach to modelling pulse mode soil flushing on a Pb-contaminated soil

4noPurpose: Soil flushing can represent a suitable technology in remediation of soils, sediments and sludge contaminated by persistent species (e.g. toxic metal). This paper presents a model specifically developed to evaluate the feasibility of chelating agent-enhanced flushing. The model, here applied to the remediation of real Pb-contaminated soils, was conceived also to simulate an innovative pulse-mode soil flushing technique. Materials and methods: The soil flushing application was firstly carried out through columns laboratory experiments. Columns were filled with a real Pb-contaminated soil (3,000 mg kg−1 of dry soil) and flushing was operated in a pulse mode with different chelating agent dosages (3 and 4.3 mmol kg−1soil). Experimental results were used to calibrate and validate the developed reactive transport model that accounts for transport of ethylenediamine tetraacetic acid (EDTA) and EDTA–Pb chelate complexes, Pb residual concentration on soil and the reduction in permeability by soil dissolution. Determination of hydrodynamic and hydrodispersive parameters was carried out through a numerical approach incorporating the use of neural network as interpolating function of breakthrough data obtained by a tracer test. Results and discussion: The EDTA dosage strongly influenced the efficiency in Pb extraction and soil permeability. Cumulative extractions of Pb were found to be 20 and 29 % for the EDTA concentrations of 3 and 4.3 mmol/kg of dry soil, respectively. The soil dissolution caused a significant flow rate decrease, as a consequence of the increase in chelating agent concentration. Therefore the recovery phase duration increased from 738 to 2,080 h. The ability of the model in simulating all the examined phenomena is confirmed by a good fit with experimental results in terms of (a) soil permeability reduction, (b) eluted Pb and (c) residual Pb in the soil. Conclusions: Results highlighted as the model, supported by a preliminary and careful characterization of the soil, can be useful to assess the feasibility of the flushing treatment (avoiding soil clogging) and to address the choice of the operating parameters (flow rate, chelating agent dosage and application method). On the basis of the present research results, a protocol is suggested for in situ soil pulse–flushing application.openLuciano, A.; Viotti, P.; Torretta, V.; Mancini, G.Luciano, A.; Viotti, P.; Torretta, Vincenzo; Mancini, G

Potential use of modulators of oxidative stress as add-on therapy in patients with anxiety disorders

It is known that an increased oxidative stress is present in a wide range of diseases and, given the vulnerability of the central nervous system, its involvement has been in particular investigated in neurological and psychiatric diseases, including anxiety disorders. In this review we analyse the studies that have been conducted on the effects of oxidative stress modulators in anxiety, focusing on their possible clinical use. While preclinical studies have shown a clear anxiolytic-like effect of different oxidative stress modulators, less significant results have been obtained from clinical studies. After having reviewed the possible reasons for the discrepancy between preclinical and clinical data, we encourage further studies aimed at better investigating the utility of the modulation of oxidative stress in humans, as adjunctive therapy of the traditional integrated psychotherapeutic and pharmacological approach

Oregano essential oils: Antimicrobial activity and its application to films based on cornstarch and glycerol

This trend has led to research on the development of new biodegradable packaging materials from natural polymers also suggests that several materials may be incorporated into edible films and have influence on the mechanical, protective and sensory properties. The objective of this work was to characterize oregano essential oils and incorporated edible films made with cornstarch and glycerol. The oregano essential oil obtain the raw material used was the variety Italian Oregano or Origanum majorana using a Clevenger-type apparatus. The study included the refractive index, chemical composition, color at day 0 and day 10 and antimicrobial activity of Salmonella Enteritidis and Escherichia Coli O157:H7. The films were prepared according to the method of casting, cornstarch, glycerol (plasticizer) and water. To assess the effect of the composition on the physical properties of films, the experiment was arranged in a 22 factorial design, with one central point. It analyzed the transfer of water vapor (Method ASTM E96-92) and color. The film which showed the best characteristics was selected; subsequently oregano essential oil was added. The refractive index of the oregano essential oils obtained from the various extractions varied between 1.4875 and 1.4981. There was a significant difference (P<0.05) between the parameters a* and b* between day 0 and day 10. According to gas chromatography analysis, 52 compounds were identified in oregano essential oil, thymol (31.96%) and carvacrol (0.66%) phenols. The test antimicrobial activity, showed that Salmonella Enteritidis and Escherichia Coli O157:H7 were extremely sensitive to pure essential oil. The films obtained were transparent, presented homogeneous and compact surfaces. The values of permeability to water vapor were between 1.93 x 10-12 and 9.85 x 10-12 (g/m.s.Pa). The Analysis of Variance (ANOVA) indicated a significant differences between the different formulation (P<0.05). The incorporation of oregano essential oil at the formulations influenced the permeability presenting more or less resistant to the passage of water vapor. About the color, incorporating essential oil did not affect the appearance and did not show strong antibacterial activity at the concentration at which it was decided to work.Fil: Córsico, Francisco Armando. Universidad Nacional de Entre Ríos. Facultad de Bromatología; ArgentinaFil: Larrosa, Virginia Judit. Universidad Nacional de Entre Ríos. Facultad de Bromatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: López Noviello, Luciano Hernán. Universidad Nacional de Entre Ríos. Facultad de Bromatología; ArgentinaFil: Altamirano, Alfonsina. Universidad Nacional de Entre Ríos. Facultad de Bromatología; ArgentinaFil: Naef, Antonella. Universidad Nacional de Entre Ríos. Facultad de Bromatología; ArgentinaFil: Alfaro, Cristina. Universidad Nacional de Entre Ríos. Facultad de Bromatología; ArgentinaFil: Garzón, Claudia Guadalupe. Universidad Nacional de Entre Ríos. Facultad de Bromatología; ArgentinaFil: Lound, Liliana Haydee. Universidad Nacional de Entre Ríos. Facultad de Bromatología; Argentin

Relative bioefficacy of RRR-α-tocopherol versus all-rac-α-tocopherol in in vitro models

The aim of this study was to evaluate the in vitro relative bioefficacy of RRR-α-tocopherol (RRR- α-T) versus all-rac-α-tocopherol (all-rac-α-T) in counteracting the cytotoxic effect induced by H2O2 in Bovine Mammary Epithelium – University of Vermont (BME-UV1) and Madin-Darby Canine Kidney (MDCK) cells. The range of RRR- α-T and all-rac- α-T concentrations selected for the oxidative challenge experiments was 100µM - 1nM. To study the bioefficacy of RRR- α-T and all-rac- α-T, MTT and LDH tests were performed. Cells were pre-incubated for 3 h with  selected a-tocopherol concentrations and then exposed to increasing H2O2 concentrations ranging from 125 to 750µM for the following 24h. Concerning the cell viability, the pre-treatments with 100µM of RRR- α-T and 100µM all-rac-α-T were able to significantly (P&lt;0.05) counteract the effect induced by 750 µM of H2O2 in BME-UV1. In MDCK the pre-treatment with 1nM of all-rac-α-T was able to significantly (P&lt;0.05) reduce the effect of 125 and 150 mM H2O2. In MDCK cells, the pre-incubation with all-rac-α-T determines a significant reduction of the membrane damage, induced by 175 µM of H2O2. In conclusion, RRR-α-T and all-rac-α-T have shown the ability to counteract the oxidative effects of H2O2, however further investigation will help to better understand their specific mechanism of action in vitro.  

Monomolecular G-quadruplex structures with inversion of polarity sites: new topologies and potentiality

In this paper, we report investigations, based on circular dichroism, nuclear magnetic resonance spectroscopy and electrophoresis methods, on three oligonucleotide sequences, each containing one 3- 3 and two 5-5 inversion of polarity sites, and four G-runs with a variable number of residues, namely two, three and four (mTG2T, mTG3T andmTG4T with sequence 3-TGnT-5-5-TGnT-3-3-TGnT-5-5-TGnT-3 in which n = 2, 3 and 4, respectively), in comparison with their canonical counterparts (TGnT)4 (n = 2, 3 and 4). Oligonucleotides mTG3T and mTG4 T have been proven to form very stable unprecedented monomolecular parallel G-quadruplex structures, characterized by three side loops containing the inversion of polarity sites. Both G-quadruplexes have shown an all-syn G-tetrad, while the other guanosines adopt anti glycosidic conformations. All oligonucleotides investigated have shown a noteworthy antiproliferative activity against lung cancer cell line Calu 6 and colorectal cancer cell line HCT-116 p53−/−. Interestingly, mTG3T andmTG4T have proven to be mostly resistant to nucleases in a fetal bovine serum assay. The whole of the data suggest the involvement of specific pathways and targets for the biological activity

The Red Blood Cell as a Gender-Associated Biomarker in Metabolic Syndrome: A Pilot Study

In the present pilot study (56 patients), some red blood cell parameters in samples from patients with metabolic syndrome and subclinical atherosclerosis, but without any sign of coronary artery disease, have been analyzed. The main goal of this work was to determine, in this preclinical state, new peripheral gender-associated bioindicators of possible diagnostic or prognostic value. In particular, three different “indicators” of red blood cell injury and aging have been evaluated: glycophorin A, CD47, and phosphatidylserine externalization. Interestingly, all these determinants appeared significantly modified and displayed gender differences. These findings could provide novel and useful hints in the research for gender-based real-time bioindicators in the progression of metabolic syndrome towards coronary artery disease. Further, more extensive studies are, however, necessary in order to validate these findings