Associations between 11 epistatic models and HPV oncogenic risk.

<p>^*The epistatic models were numbered as described previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089489#pone.0089489-Hartwig1" target="_blank">[46]</a>.</p>†<p>The “_” indicates that the effect is irrespective of the allele. E.g., R72P G309_ represents the genotypic combinations R72P T309G - R72P G309G.</p>¥<p>Other: <b>3.1</b>: _72_ T309_ - R72R _309_. <b>3.2</b>: R72_ _309_ - _72_ T309T. <b>4</b>: P72_ _309_ - _72_ G309_. <b>5</b>: P72P _309_ - _72_ G309G. <b>6</b>: R72R G309_ - P72_ T309T. <b>7</b>: P72P T309_ - R72_ G309G.</p

Associations between 11 epistatic models and HPV status.

<p>^*The epistatic models were numbered as described previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089489#pone.0089489-Hartwig1" target="_blank">[46]</a>.</p>†<p>The “_” indicates that the effect is irrespective of the allele. E.g., R72P G309_ represents the genotypic combinations R72P T309G - R72P G309G.</p>¥<p>Other: <b>3.1</b>:_72_ T309_ - R72R _309_. <b>3.2</b>: R72_ _309_ - _72_ T309T. <b>4</b>: P72_ _309_ - _72_ G309_. <b>5</b>: P72P _309_ - _72_ G309G. <b>6</b>: R72R G309_ - P72_ T309T. <b>7</b>: P72P T309_ - R72_ G309G.</p

Evidence for an Epistatic Effect between <i>TP53</i> R72P and <i>MDM2</i> T309G SNPs in HIV Infection: A Cross-Sectional Study in Women from South Brazil

<div><p>Objective</p><p>To investigate the associations of <i>TP53</i> R72P and <i>MDM2</i> T309G SNPs with HPV infection status, HPV oncogenic risk and HIV infection status.</p><p>Design</p><p>Cross-sectional study combining two groups (150 HIV-negative and 100 HIV-positive) of women.</p><p>Methods</p><p>Data was collected using a closed questionnaire. DNA was extracted from cervical samples. HPV infection status was determined by nested-PCR, and HPV oncogenic risk group by Sanger sequencing. Both SNPS were genotyped by PCR-RFLP. Crude and adjusted associations involving each exposure (R72P and T309G SNPs, as well as 13 models of epistasis) and each outcome (HPV status, HPV oncogenic risk group and HIV infection) were assessed using logistic regression.</p><p>Results</p><p>R72P SNP was protectively associated with HPV status (overdominant model), as well as T309G SNP with HPV oncogenic risk (strongest in the overdominant model). No epistatic model was associated with HPV status, but a dominant (R72P over T309G) protective epistatic effect was observed for HPV oncogenic risk. HIV status was strongly associated (risk factor) with different epistatic models, especially in models based on a visual inspection of the results. Moreover, HIV status was evidenced to be an effect mediator of the associations involving HPV oncogenic risk.</p><p>Conclusions</p><p>We found evidence for a role of R72P and T309G SNPs in HPV status and HPV oncogenic risk (respectively), and strong associations were found for an epistatic effect in HIV status. Prospective studies in larger samples are warranted to validate our findings, which point to a novel role of these SNPs in HIV infection.</p></div

Descriptive analyses of the sample, comparing the HIV groups.

<p>^*Fisher's exact test.</p>†<p>Chi-square test.</p

OR (with 95% CI) for the association (adjusted for skin color and age) between combined genotypes of the two SNPs and HIV status.

<p>OR (with 95% CI) for the association (adjusted for skin color and age) between combined genotypes of the two SNPs and HIV status.</p

Crude and adjusted associations [showing OR (95% CI) and p-values] between R72P and T309G SNPs and HPV status.

<p>^*“A” and “a” correspond to wild-type (i.e., either R72 or T309) and variant alleles (i.e., either P72 or G309), respectively.</p

Crude and adjusted associations [showing OR (95% CI) and p-values] between R72P and T309G SNPs and HPV oncogenic risk.

<p>^*“A” and “a” correspond to wild-type (i.e., either R72 or T309) and variant alleles (i.e., either P72 or G309), respectively.</p

Associations between 11 epistatic models and HIV status.

<p>^*The epistatic models were numbered as described previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089489#pone.0089489-Hartwig1" target="_blank">[46]</a>.</p>†<p>The “_” indicates that the effect is irrespective of the allele. E.g., R72P G309_ represents the genotypic combinations R72P T309G - R72P G309G.</p>¥<p>Other: <b>3.1</b>: _72_ T309_ - R72R _309_. <b>3.2</b>: R72_ _309_ - _72_ T309T. <b>4</b>: P72_ _309_ - _72_ G309_. <b>5</b>: P72P _309_ - _72_ G309G. <b>6</b>: R72R G309_ - P72_ T309T. <b>7</b>: P72P T309_ - R72_ G309G.</p

Effects of Two Types of Melatonin-Loaded Nanocapsules with Distinct Supramolecular Structures: Polymeric (NC) and Lipid-Core Nanocapsules (LNC) on Bovine Embryo Culture Model

<div><p>Melatonin has been used as a supplement in culture medium to improve the efficiency of <i>in vitro</i> produced mammalian embryos. Through its ability to scavenge toxic oxygen derivatives and regulate cellular mRNA levels for antioxidant enzymes, this molecule has been shown to play a protective role against damage by free radicals, to which <i>in vitro</i> cultured embryos are exposed during early development. <i>In vivo</i> and <i>in vitro</i> studies have been performed showing that the use of nanocapsules as active substances carriers increases stability, bioavailability and biodistribution of drugs, such as melatonin, to the cells and tissues, improving their antioxidant properties. These properties can be modulated through the manipulation of formula composition, especially in relation to the supramolecular structures of the nanocapsule core and the surface area that greatly influences drug release mechanisms in biological environments. This study aimed to evaluate the effects of two types of melatonin-loaded nanocapsules with distinct supramolecular structures, polymeric (NC) and lipid-core (LNC) nanocapsules, on <i>in vitro</i> cultured bovine embryos. Embryonic development, apoptosis, reactive oxygen species (ROS) production, and mRNA levels of genes involved in cell apoptosis, ROS and cell pluripotency were evaluated after supplementation of culture medium with non-encapsulated melatonin (Mel), melatonin-loaded polymeric nanocapsules (Mel-NC) and melatonin-loaded lipid-core nanocapsules (Mel-LNC) at 10⁻⁶, 10⁻⁹, and 10⁻¹² M drug concentrations. The highest hatching rate was observed in embryos treated with 10⁻⁹ M Mel-LNC. When compared to Mel and Mel-NC treatments at the same concentration (10⁻⁹ M), Mel-LNC increased embryo cell number, decreased cell apoptosis and ROS levels, down-regulated mRNA levels of <i>BAX</i>, <i>CASP3</i>, and <i>SHC1</i> genes, and up-regulated mRNA levels of <i>CAT</i> and <i>SOD2</i> genes. These findings indicate that nanoencapsulation with LNC increases the protective effects of melatonin against oxidative stress and cell apoptosis during <i>in vitro</i> embryo culture in bovine species.</p></div

Effects of free and nanoencapsulated melatonin (10⁻⁹ M) on the relative mRNA abundance of oxidative stress-related genes.

<p>Data represent mean ± S.E.M. Different letters (a, b and c) indicate significant differences between groups (P< 0.05).</p