Effect of Resveratrol-Related Stilbenoids on Biomembrane Models

The interactions of the two resveratrol analogues 2-hydroxy-3,5,3′,5′-tetramethoxystilbene (<b>4</b>) and 2-hydroxy-3,5,3′,4′-tetramethoxystilbene (<b>5</b>) with model biomembranes were studied. The aim of this investigation was to highlight possible differences in the interactions with such biomembranes related to the minimal structural differences between these isomeric stilbenoids. In particular, different experiments on stilbenoid/biomembrane model systems using both differential scanning calorimetry (DSC) and Langmuir–Blodgett techniques were carried out to evaluate stilbenoid/multilamellar vesicle and stilbenoid/phospholipid monolayer interactions, respectively. Dimyristoylphosphatidylcholine was used as constituent of the biomembrane models and permitted the experiments to be carried out at 37 °C, close to body temperature. Kinetic studies were also run by DSC to evaluate the uptake of the resveratrol derivatives by the biomembrane model in an aqueous medium and when transported by a lipophilic carrier. The results indicated that both of the resveratrol analogues influenced the behavior of multilamellar vesicles and monolayers, biomembrane models, with <b>4</b> producing a larger effect than <b>5</b>. These results are useful for better understanding the mechanism of action of these compounds. Moreover, the kinetic results could be of importance for future design of lipophilic delivery systems for these stilbenoids

Anticlastogenic Effect in Human Lymphocytes by the Sodium Salt of 3,4-Secoisopimar-4(18),7,15-trien-3-oic Acid

The ability of the sodium salt of 3,4-secoisopimar-4(18),7,15-trien-3-oic acid (<b>1</b>), a diterpenoid obtained from <i>Salvia cinnabarina</i>, to inhibit the genotoxic effect of ethyl methanesulfonate (a clastogenic agent) and colcemid (an aneugenic agent), was studied using a micronucleus assay on cultured human lymphocytes. Cells were treated with <b>1</b> before (pretreatment), during (co-treatment), and after (post-treatment) treatment with the mutagens, in order to investigate the type of antimutagenic activity (desmutagenic or bioantimutagenic) manifested. In the range of concentrations tested (0.3–330 μM) <b>1</b> reduced significantly the frequency of micronuclei induced by ethyl methanesulfonate, in both pre- and co-treatment protocols (up to 74% and 70% of reduction, respectively), showing an anticlastogenic activity. Conversely, <b>1</b> did not inhibit the effect of colcemid in all treatments. The nuclear division index value of lymphocytes was not affected by treatment with <b>1</b>, thus demonstrating that the anticlastogenic effect of <b>1</b> was not due to a cytotoxic effect. On the basis of the results obtained, it can be hypothesized that <b>1</b> exerts its anticlastogenic activity against ethyl methanesulfonate by a desmutagenic mechanism, possibly by chemical inactivation of the mutagen

MOESM1 of The impact of antiretroviral therapy on iron homeostasis and inflammation markers in HIV-infected patients with mild anemia

Additional file 1. Pearson correlation analysis. Pearson correlation analysis between variables considered in this study (Hb, HIV-related factors, markers of iron homeostasis, of immune activation and inflammation). In bold Pearson correlation coefficients with rho > |0.7| and p values < 0.05 are shown

Areas under the ROC curve according to different risk scores of CVD incidence.

<p>Areas under the ROC curve according to different risk scores of CVD incidence.</p

Hazard ratio for NLR ≥ 1.2 compared to NLR < 1.2 in predicting cardiovascular event incidence in five models.

<p>Hazard ratio for NLR ≥ 1.2 compared to NLR < 1.2 in predicting cardiovascular event incidence in five models.</p

Risk of CVD event (Hazard Ratio) according to NLR distribution.

<p>NLR was modeled by cubic spline (solid line) with three knots in Cox regression model adjusted for age, sex, intravenous drug use, diabetes and tobacco smoking as fixed covariates, and CD4 cell count, antiretroviral therapy, presence of hypertension, SBP, total cholesterol and HDL as time dependent covariates. The reference value is 1.2. The 95% confidence intervals are shown as dashed lines. <i>Vertical axes</i> have a <i>logarithmic scale</i>. Abbreviations: NLR, neutrophil to lymphocyte ratio; SBP, systolic blood pressure; HDL, high density lipoprotein.</p

Cumulative incidence CVD curves in HIV-infected subjects with NLR<1.2 and NLR ≥1.2.

<p>Abbreviation: NLR, neutrophil to lymphocyte ratio.</p

Patient characteristics.

<p>List of abbreviations: AIDS, acquired immunodeficiency syndrome; HAART, highly-active antiretroviral treatment; HBsAg, hepatitis B surface antigen; HCV-Ab, hepatitis C virus antibodies; HIV, human immunodeficiency virus; INR, immunological non-responders; IQR, interquartile range; IR, Immunological responders; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.</p><p>Patient characteristics.</p

Proportion of patients remaining free from severe non AIDS-related event.

<p>List of abbreviations: AIDS, acquired immunodeficiency syndrome; HAART, Highly-active antiretroviral therapy.</p

Multivariable Cox Proportional Hazard Models for Time to first AIDS-defining event or severe non AIDS-defining event or death.

<p>List of abbreviations: AIDS, acquired immunodeficiency syndrome; CI, confidence interval; HAART, highly-active antiretroviral treatment; HBsAg, hepatitis B surface antigen; HCV-Ab, hepatitis C virus antibodies; HIV, human immunodeficiency virus; INR, immunological non-responders; IR, Immunological responders; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.</p><p>¹ The first model was adjusted for age and gender.</p><p>² The second model was adjusted for age, gender, intravenous drug use as route of HIV transmission, pre-HAART CD4+ T-cell count, occurrence of AIDS-defining events and immunological response (Immunological non responders at year 1 <i>versus</i> responders). Occurrence of AIDS-defining event during follow-up was considered as time-dependent variable</p><p>* Estimates for HCV-Ab positivity were not adjusted for intravenous drug use as route of HIV transmission, due to high correlation.</p><p>Multivariable Cox Proportional Hazard Models for Time to first AIDS-defining event or severe non AIDS-defining event or death.</p