The initial months of antiretroviral therapy and its influence on AGEs, HMGB1, and sRAGE levels in asymptomatic HIV-infected individuals

The development of the typical comorbidities of aging which currently affects people living with HIV/AIDS (PLWHA) can be partially ascribed to the persistent immune activation and chronic inflammation characterizing these individuals. The aim of this study was to analyze the effect exerted by combined antiretroviral therapy (cART) administration on plasma levels of HMGB1 (high mobility group box protein-1), AGEs (advanced glycation end products), their soluble receptor sRAGE, cytokines, C-reactive protein (CRP), and some metabolic markers in asymptomatic PLWHA. Analyses were performed longitudinally in 30 PLWHA, before and about 6\u201312 months after cART initiation. We observed that lower levels of AGEs in post-cART group were accompanied by an increase of CRP and triglyceride levels already in the early months of therapy. Because of the current ever-earlier recommendations to start cART and its prolonged use, these and other markers should be investigated in order to monitor and postpone the appearance of non-AIDS comorbidities in PLWHA

Antiretroviral therapy initiation alters the redox system of asymptomatic HIV-Infected individuals

Background. The combination antiretroviral therapy (cART) increases the oxidative stress in HIV-infected people, which in turn favors the onset and aggravation of non-AIDS comorbidities, a common situation affecting these individuals. We aimed to evaluate the influence of cART initiation on oxidative stress parameters. This is a longitudinal study including 30 asymptomatic patients divided according to their CD4+ T cell count (G1: 500 cell/mL) before (M0) and after (M1) cART initiation. We analyzed total antioxidant capacity (TAC), fat-soluble vitamins, malondialdehyde, 8-isoprostane, and DNA damage. Results. Results showed a decrease in TAC, retinol, \u3b1-tocopherol, and some carotenoids, in addition to a significant increase in DNA damage at M1. These changes were more evident in G2 subjects. Moreover, there was a significant 8-isoprostane increase at M1 in individuals belonging to G1. Conclusion. The results indicate that cART interfered in the redox system, mainly by reducing the antioxidant defenses. In addition, patients who had CD4+ T counts higher than 500 cells/mm3 showed more susceptibility to genotoxicity, while patients with less CD4+ T counts displayed more damage triggered by lipoperoxidation. Considering the early beginning of cART, its chronic use, and its capacity to alter the redox status, further long-term studies on larger cohorts are needed to define the best time to initiate therapy and to investigate new strategies to delay the development of non-AIDS diseases

The VANDELS ESO public spectroscopic survey

VANDELS is a uniquely deep spectroscopic survey of high-redshift galaxies with the VIMOS spectrograph on ESO’s Very Large Telescope (VLT). The survey has obtained ultradeep optical (0.48 < λ < 1.0 μ m) spectroscopy of ≃2100 galaxies within the redshift interval 1.0 ≤ z ≤ 7.0, over a total area of ≃0.2 deg2 centred on the CANDELS Ultra Deep Survey and Chandra Deep Field South fields. Based on accurate photometric redshift pre-selection, 85 per cent of the galaxies targeted by VANDELS were selected to be at z ≥ 3. Exploiting the red sensitivity of the refurbished VIMOS spectrograph, the fundamental aim of the survey is to provide the high-signal-to-noise ratio spectra necessary to measure key physical properties such as stellar population ages, masses, metallicities, and outflow velocities from detailed absorption-line studies. Using integration times calculated to produce an approximately constant signal-to-noise ratio (20 < tint< 80 h), the VANDELS survey targeted: (a) bright star-forming galaxies at 2.4 ≤ z ≤ 5.5, (b) massive quiescent galaxies at 1.0 ≤ z ≤ 2.5, (c) fainter star-forming galaxies at 3.0 ≤ z ≤ 7.0, and (d) X-ray/Spitzer-selected active galactic nuclei and Herschel-detected galaxies. By targeting two extragalactic survey fields with superb multiwavelength imaging data, VANDELS will produce a unique legacy data set for exploring the physics underpinning high-redshift galaxy evolution. In this paper, we provide an overview of the VANDELS survey designed to support the science exploitation of the first ESO public data release, focusing on the scientific motivation, survey design, and target selection

Identification of a Specific miRNA Profile in HIV-Exposed Seronegative Individuals

Objective: MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression that play important roles in viral infections. Alterations of specific miRNAs are described in HIV infection, suggesting a role for miRNAs in pathogenesis of this disease. We verified whether a particular miRNA signature could be identified in natural resistance to HIV-1. Methods: Expression level of 84 miRNAs was analyzed by RT-qPCR in plasma and unstimulated peripheral blood mononuclear cell (PBMC) of 30 seronegative individuals repeatedly exposed to HIV-1 (HESN), 30 HIV seropositive subjects (HIV+), and 30 healthy controls (HC). Results were confirmed by individual RT-qPCR in in vitro HIV-1-infected PBMC and in their cell culture medium. Dicer and Drosha expression was analyzed in basal PBMC. Results: Whereas Dicer and Drosha expression was comparable in HESN, HIV+ and HC, several miRNAs were upregulated both in HESN and HIV+ compared with HC. Furthermore, miRNA-29a and miR-223 were upregulated in both unstimulated PBMC and plasma of HESN alone; their expression was reduced upon in vitro HIV-1 infection of HESN PBMC indicating that, upon infection, they are secreted in the extracellular milieu. These results were confirmed by individual qPCR. Conclusions: Our studies demonstrate that HIV-1 exposure modifies miRNAs expression even in the absence of productive infection. Because those miRNAs that are specifically increased only in HESN have been known to reduce HIV-1 replication, their modulation could represent an important mechanism in resistance to HIV-1 infection