Sex-Dependent Mediation of Leptin in the Association of Perilipin Polymorphisms with BMI and Plasma Lipid Levels in Children

Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6–8 years. Our results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the PLIN SNPs with these variables

Cardiovascular Damage in COVID-19: Therapeutic Approaches Targeting the Renin-Angiotensin-Aldosterone System

Coronavirus disease 2019 (COVID-19) is usually more severe and associated with worst outcomes in individuals with pre-existing cardiovascular pathologies, including hypertension or atherothrombosis. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can differentially infect multiple tissues (i.e., lung, vessel, heart, liver) in different stages of disease, and in an age- and sex-dependent manner. In particular, cardiovascular (CV) cells (e.g., endothelial cells, cardiomyocytes) could be directly infected and indirectly disturbed by systemic alterations, leading to hyperinflammatory, apoptotic, thrombotic, and vasoconstrictive responses. Until now, hundreds of clinical trials are testing antivirals and immunomodulators to decrease SARS-CoV-2 infection or related systemic anomalies. However, new therapies targeting the CV system might reduce the severity and lethality of disease. In this line, activation of the non-canonical pathway of the renin-angiotensin-aldosterone system (RAAS) could improve CV homeostasis under COVID-19. In particular, treatments with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) may help to reduce hyperinflammation and viral propagation, while infusion of soluble ACE2 may trap plasma viral particles and increase cardioprotective Ang-(1–9) and Ang-(1–7) peptides. The association of specific ACE2 polymorphisms with increased susceptibility of infection and related CV pathologies suggests potential genetic therapies. Moreover, specific agonists of Ang-(1–7) receptor could counter-regulate the hypertensive, hyperinflammatory, and hypercoagulable responses. Interestingly, sex hormones could also regulate all these RAAS components. Therefore, while waiting for an efficient vaccine, we suggest further investigations on the non-canonical RAAS pathway to reduce cardiovascular damage and mortality in COVID-19 patients

Addition of Probiotics to Anti-Obesity Therapy by Percutaneous Electrical Stimulation of Dermatome T6. A Pilot Study

Obesity is becoming a pandemic and percutaneous electrical stimulation (PENS) of dermatome T6 has been demonstrated to reduce stomach motility and appetite, allowing greater weight loss than isolated hypocaloric diets. However, modulation of intestinal microbiota could improve this effect and control cardiovascular risk factors. Our objective was to test whether addition of probiotics could improve weight loss and cardiovascular risk factors in obese subjects after PENS and a hypocaloric diet. A pilot prospective study was performed in patients (n = 20) with a body mass index (BMI) > 30 kg/m2. Half of them underwent ten weeks of PENS in conjunction with a hypocaloric diet (PENS-Diet), and the other half was treated with a PENS-Diet plus multistrain probiotics (L. plantarum LP115, B. brevis B3, and L. acidophilus LA14) administration. Fecal samples were obtained before and after interventions. The weight loss and changes in blood pressure, glycemic and lipid profile, and in gut microbiota were investigated. Weight loss was significantly higher (16.2 vs. 11.1 kg, p = 0.022), whereas glycated hemoglobin and triglycerides were lower (-0.46 vs. -0.05%, p = 0.032, and -47.0 vs. -8.5 mg/dL, p = 0.002, respectively) in patients receiving PENS-Diet + probiotics compared with those with a PENS-Diet. Moreover, an enrichment of anti-obesogenic bacteria, including Bifidobacterium spp, Akkermansia spp, Prevotella spp, and the attenuation of the Firmicutes/Bacteroidetes ratio were noted in fecal samples after probiotics administration. In obese patients, the addition of probiotics to a PENS intervention under a hypocaloric diet could further improve weight loss and glycemic and lipid profile in parallel to the amelioration of gut dysbiosis.Sin financiación3.390 JCR (2020) Q1, 42/176 Public, Environmental & Occupational Health0.747 SJR (2020) Q2, 50/136 Health, Toxicology and MutagenesisNo data IDR 2020UE

Acción adyuvante de esporas de Bacillus subtilis por vía mucosa

Las esporas de Bacillus subtilis, generalmente reconocidas como seguras, han recibido una creciente atención en aplicaciones biotecnológicas en formulaciones vacunales, sobre todo como adyuvantes. Este trabajo presenta una revisión actualizada de la acción adyuvante de las esporas de B. subtilis y conjuntamente se expone nuestra experiencia por vía oral (o.r) e intranasal (i.n) como adyuvante frente antígenos modelos ovoalbúmina (Ova) y toxoide tetánico (TT). Se realizó una revisión documental sobre B. subtilis, adyuvante, vacuna y vía mucosal en MEDLINE a través de PubMed; también se revisaron las bases de datos SciELO y LILACS. Para la exploración de la capacidad adyuvante se trabajó con esporas de B. subtilis (cepa RG 4365). Se inmunizaron ratones Balb/c por vía mucosal con esporas coadministradas con los antígenos modelos, y se midió las respuesta de anticuerpos específicos en suero, saliva y heces por método de ELISA. La revisión realizada evidenció la existencia de varios trabajos que utilizan las esporas de B. subtilis por diferentes metodologías y vías de administración como adyuvante, siendo la expresión de antígenos recombinantes la más utilizada, así como la vía o.r entre la aplicación mucosa. En nuestro trabajo se obtuvo un aumento de la respuesta sérica de IgG, subclases IgG1 e IgG2a y de IgA específicos en saliva y heces en los grupos inmunizados con esporas coadministradas con Ova y con TT por ambas vías, significativamente superior a los grupos controles (p<0,05). Estos datos sugieren que las esporas son eficientes adyuvantes pues aumentan la respuesta inmune humoral sistémica y mucosal y resalta su potencial clínico en futuras vacunas mucosales

Activity adjuvant of Bacillus subtilis spores for mucosal route

Las esporas de Bacillus subtilis, generalmente reconocidas como seguras, han recibido una creciente atención en aplicaciones biotecnológicas en formulaciones vacunales, sobre todo como adyuvantes. Este trabajo presenta una revisión actualizada de la acción adyuvante de las esporas de B. subtilis y conjuntamente se expone nuestra experiencia por vía oral (o.r) e intranasal (i.n) como adyuvante frente antígenos modelos ovoalbúmina (Ova) y toxoide tetánico (TT). Se realizó una revisión documental sobre B. subtilis, adyuvante, vacuna y vía mucosal en MEDLINE a través de PubMed; también se revisaron las bases de datos SciELO y LILACS. Para la exploración de la capacidad adyuvante se trabajó con esporas de B. subtilis (cepa RG 4365). Se inmunizaron ratones Balb/c por vía mucosal con esporas coadministradas con los antígenos modelos, y se midió las respuesta de anticuerpos específicos en suero, saliva y heces por método de ELISA. La revisión realizada evidenció la existencia de varios trabajos que utilizan las esporas de B. subtilis por diferentes metodologías y vías de administración como adyuvante, siendo la expresión de antígenos recombinantes la más utilizada, así como la vía o.r entre la aplicación mucosa. En nuestro trabajo se obtuvo un aumento de la respuesta sérica de IgG, subclases IgG1 e IgG2a y de IgA específicos en saliva y heces en los grupos inmunizados con esporas coadministradas con Ova y con TT por ambas vías, significativamente superior a los grupos controles (p<0,05). Estos datos sugieren que las esporas son eficientes adyuvantes pues aumentan la respuesta inmune humoral sistémica y mucosal y resalta su potencial clínico en futuras vacunas mucosales.Bacillus subtilis spores generally considered safe, have received growing attention due to their potential biotechnological applications including vaccine formulations, particularly as vaccine adjuvants. In the present review we present the status of the adjuvanticity of the spore B. subtilis for mucosal route and our experience regarding its adjuvant activity induced against two model antigens, Tetanus Toxoid (TT) and ovalbumin (Ova) for oral (o.r) and intranasal (i.n) immunization. A document review on B. subtilis, adjuvant, vaccine and mucosal route was carried out in MEDLINE by PubMed, SciELO and LILACS databases. B. subtilis spores (RG 4365) were used for the exploration of the adjuvant activity. Balb/c mice were immunized by i.n and o.r route with TT or Ova combined with B. subtilis spores and specific antibody response in serum, saliva and fecal were measured by ELISA. This review showed the existence of several papers using B. subtilis spores as adjuvant by different methodologies and administration routes, being the expression of recombinant antigens and the the o.r route the most widely used. In our work we found an increase of seric response of IgG, subclass IgG1 and IgG2a and specific IgA in saliva and feces in groups immunized with spores coadministered with Ova and TT by both routes, which was significantly superior to control groups (p<0.05). These data suggest that spores are an efficient mucosal and systemic adjuvant for enhancing humoral immune responses and highlight their clinical potential for future mucosal vaccines.Fil: Tub Chafer, Fabiana. Universidad de Ciencias Médicas de La Habana. Facultad de Ciencias Médicas Victoria de Girón . Instituto de Ciencias Básicas y Preclínicas; CubaFil: Reyes Díaz, Laura María. Instituto Finlay; CubaFil: Vega García, Irma Gudelia. Universidad de Ciencias Médicas de La Habana. Facultad de Ciencias Médicas Victoria de Girón . Instituto de Ciencias Básicas y Preclínicas; CubaFil: González Aznar, Elizabeth. Instituto Finlay; CubaFil: Otero Alfaro, Oscar. Instituto Finlay; CubaFil: Lumpuy Castillo, Jairo. Universidad de Ciencias Médicas de La Habana. Facultad de Ciencias Médicas Victoria de Girón . Instituto de Ciencias Básicas y Preclínicas; CubaFil: Grau, Roberto Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; ArgentinaFil: Pérez, Oliver. Universidad de Ciencias Médicas de La Habana. Facultad de Ciencias Médicas Victoria de Girón . Instituto de Ciencias Básicas y Preclínicas; Cub

Absence of High Lipoprotein(a) Levels Is an Independent Predictor of Acute Myocardial Infarction without Coronary Lesions

The pathophysiological mechanisms underlying Myocardial Infarction with Non-Obstructive Coronary Artery Disease (MINOCA) are still under debate. Lipoprotein (a) [Lp(a)] has proinflammatory and prothrombotic actions and has been involved in the pathogenesis of atherosclerosis. However, no previous studies have linked Lp(a) levels with the probability of developing MINOCA. Moreover, the relationship between MINOCA and the plasma levels of other proatherogenic and proinflammatory molecules such as Interleukin-18 (IL18) and proprotein convertase subtilisin/kexin type 9 (PCSK9) has not been studied. We conducted a prospective, multicenter study involving 1042 patients with acute myocardial infarction (AMI). Seventy-six patients had no significant coronary lesions. All patients underwent plasma analysis on admission. MINOCA patients were younger (57 (47&ndash;68) vs. 61 (52&ndash;72) years; p = 0.010), more frequently female (44.7% vs. 21.0%; p &lt; 0.001), and had lower rates of diabetes and of Lp(a) &gt; 60 mg/dL (9.2% vs. 19.8%; p = 0.037) than those with coronary lesions; moreover, High Density Lipoprotein cholesterol (HDL-c) levels were higher in MINOCA patients. The absence of Lp(a) &gt; 60 mg/dL and of diabetes were independent predictors of MINOCA, as well as female sex, high HDL-c levels, and younger age. IL-18 and PCSK9 levels were not predictors of MINOCA. During a follow-up of 5.23 (2.89, 7.37) years, the independent predictors of the primary outcome (acute ischemic events or death) in the whole sample were Lp(a) &gt; 60 mg/dL, older age, low estimated Glomerular Filtration rate (eGFR), hypertension, previous heart failure (HF), coronary artery bypass graft, use of insulin, and no therapy with acetylsalicylic acid. In conclusion, in AMI patients, the absence of high Lp(a) levels, as well high HDL-c levels, were independent predictors of the inexistence of coronary artery disease. High Lp (a) levels were also an independent predictor of ischemic events or death