Análisis de la expresión de genes de respuesta inmune durante el desarrollo ontogénico de paralarvas de pulpo Octopus vulgaris criadas en cautividad

El pulpo común es una especie de gran importancia comercial, considerada como una especie emergente en acuicultura. En este trabajo se analizó el nivel de expresión de los genes inmunes TLR, C1q, Galectina, PGRP, LITAF, SERPIN, PRDX y Caspasa 3 mediante PCR cuantitativa (q-PCR) en embriones y paralarvas de O. vulgaris de edades 0, 10, 20 y 34 días. Adicionalmente, se infectaron paralarvas de 22 días con bacterias patógenas vivas Vibrio lentus y V. splendidus a 1h, 4h y 24h. El estudio del desarrollo del sistema inmune de estas paralarvas ayudará a identificar factores claves para la supervivencia y cultivo del pulpo común. Durante el desarrollo ontogénico, los embriones mostraron el menor nivel de expresión de PGRP, Caspasa 3 y PRDX. Por el contrario, C1q, Galectina y LITAF se observaron visiblemente expresados. C1q, TLR y SERPIN fueron los genes que presentaron mayor nivel de expresión en Pa0D. A partir de Pa10D se observó un notable incremento en la expresión de C1q, Galectina, PGRP y LITAF. La expresión de Caspasa3 se incrementó gradualmente desde Em. V. lentus y V. splendidus inducen un notable incremento de la expresión de C1q y PRDX entre 1h y 4h post infección. Sin embargo, durante las primeras horas de infección se observó una disminución de la expresión de Galectina, TLR, PGRP y LITAF. Particularmente la infección por V. lentus produjo una disminución de la expresión de SERPIN. Los resultados obtenidos sugieren que la capacidad del sistema inmune de reconocer patógenos y evitar infecciones es significativamente activo desde los estadíos de paralarvas recién eclosionadas. Sin embargo, se observó un aumento significativo de los genes seleccionados a partir de Pa10D.The common octopus is a species of high commercial interest and nowadays is considered as an emergent species in aquaculture. The mRNA expression level of immune-related genes (TLR, C1q, Galectin, PGRP, LITAF, SERPIN, PRDX and Caspase 3) was analyzed by Real time qPCR on embryos and paralarvae of O. vulgaris at age of 0, 10, 20 and 34 days. Additionally, paralarvae of 22 days were challenged with live Vibrio lentus and V. splendidus during a time course (1 h, 4 h and 24 h). This analysis will allow a better understanding of the developmental of immune system of these paralarvae, which will help to identify key factors for survival and culture of the common octopus. Regarding ontogeny, Em showed the lowest expression of PGRP, Caspase 3 and PRDX. In contrast, C1q, Galectin and LITAF were visibly expressed. C1q, TLR and SERPIN were highly expressed in Pa0D. A notably increase in the expression of C1q, Galectin, PGRP and LITAF began from Pa10D. Caspase 3 expression was gradually increased from Em. V. lentus and V. splendidus induced a notable expression of C1q and PRDX at 1 h and 4 h post infection (p. i.). Nevertheless, they markedly suppress the activation of Galectin, TLR, PGRP and LITAF during the first hours p.i.. Particularly, V. lentus suppressed the expression of SERPIN. The present results suggest that the ability of immune system to recognize pathogens and avoid infections is a priority in recently hatched paralarvae. However, a noticeable increase of gene expression was observed from Pa10D.0,000

Selection of reliable reference genes for RT-qPCR studies in Octopus vulgaris paralarvae during development and immune-stimulation

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Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata 35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.gov; Unique identifier: NCT01663402.URL: https://www

Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes