Cytokine and microbiota profiles in obesity-related hypertension patients

BackgroundSystemic arterial hypertension is linked to a heightened risk of cardiovascular diseases on a global scale. In Mexico, nearly half of adults in vulnerable conditions experience hypertension. Imbalance in the oral and intestinal microbiota composition has been observed in patients with hypertension, documented by a decrease of bacteria producing short-chain fatty acids, which play a critical role in blood pressure regulation.AimTo examine the cytokines’ profile and assess the characteristics of oral and gut microbiota in obesity-related hypertension in Mexican patients.MethodsA cross-sectional, observational, and analytical study was carried out. Twenty-two patients were categorized by their body mass index (BMI) as overweight and obese, and the diagnosis of primary hypertension. DNA from supragingival dental plaque and feces samples was used to carry out 16S rRNA sequencing. Additionally, 13 cytokines were quantified.ResultsIn the oral microbiota, Kluyvera was found to be significantly enriched in obese compared to overweight patients. Instead, the gut microbiota was dominated by Firmicutes. However, the correlation between certain genera and proinflammatory cytokines was noted.ConclusionThis exploratory study provides insights into the complex relationship between the oral and gut microbiota and their association with systemic inflammation in obesity-related hypertension

Proteína C reactiva: aspectos cardiovasculares de una proteína de fase aguda

La proteína C reactiva (PCR) es una proteína inespecífica de fase aguda, utilizada como una medida de inflamación durante décadas. Recientemente se ha propuesto como un marcador de aterogénesis y como un predictor para el desarrollo de eventos cardiovasculares adversos a futuro. La PCR se une a lipoproteínas alteradas y facilita su remoción por los fagocitos, además de activar parcialmente el sistema del complemento. Los niveles elevados de PCR pueden producir efectos directos sobre las células vasculares, incluyendo inducción de citocinas y factores protrombóticos. Aunque inicialmente se había señalado una fuerte asociación entre los niveles de PCR y eventos cardiovasculares futuros, un meta-análisis reciente y varios estudios prospectivos han mostrado que esta asociación, si bien existe, pudiera ser más débil que lo descrito inicialmente. La terapia con estatinas en pacientes con enfermedad arterial coronaria ha mostrado reducir los desenlaces cardiovasculares adversos en asociación con una reducción de los niveles séricos de PCR, independientemente de su efecto sobre el perfil de lípidos

Impacto intraoperatorio de la ultrafiltración modificada en pacientes pediátricos sometidos a cirugía cardíaca con circulación extracorpórea

ResumenIntroducción y objetivosEs controversial el uso de ultrafiltración modificada en cirugía cardíaca pediátrica con bomba de circulación extracorpórea (CEC) para disminuir la respuesta inflamatoria sistémica, hemoconcentrar y remover el exceso de líquido. El objetivo de este estudio es demostrar en el período intraoperatorio la utilidad de este método para la remoción de sustancias proinflamatorias desencadenadas por la bomba en pacientes pediátricos no neonatales operados por cardiopatías congénitas simples. Adicionalmente, se pretende averiguar su efecto sobre la hemoconcentración y la remoción del exceso de líquido y lactato.MétodosSe diseñó un ensayo clínico en pacientes pediátricos no neonatales con peso > 5kg con cardiopatías congénitas simples que se operaron con el uso de bomba en el período de un año. En forma aleatoria, se conformó un grupo problema (con ultrafiltración modificada) y un grupo control (sin ella), y se tomaron muestras para medir concentraciones de interleucinas (IL) (6 y 10) y de fracciones 3d y 4d del complemento, en los siguientes tiempos: basal, antes de bomba, después de bomba, después de la ultrafiltración y del ultrafiltrado, y al salir de quirófano. Los efectos finales se definieron en términos de morbimortalidad, remoción de sustancias proinflamatorias, lactato, balance hídrico y hemoconcentración.ResultadosSe enroló a 13 pacientes al grupo problema y 15 al grupo control. Observamos una menor concentración sérica de IL-6, IL-10 y lactato post-CEC en el grupo problema, al igual que una mayor remoción de líquido, lactato y de C4d en el ultrafiltrado.ConclusionesLa ultrafiltración modificada puede beneficiar a los pacientes pediátricos no neonatales con cardiopatía congénita operados con bomba porque es capaz de disminuir la concentración sérica de IL-6, IL-10 y lactato post-CEC. Adicionalmente, puede ayudar a filtrar C4d y a remover el exceso de líquido que promovería una mayor hemoconcentración, por lo que se recomienda su uso rutinario cuando las condiciones hemodinámicas lo permitan.AbstractIntroduction and objectivesThe use of modified ultrafiltration procedure in paediatric cardiac surgery with cardiopulmonary bypass in order to reduce the systemic inflammatory response is controversial. The aim of this study is to demonstrate the usefulness of this procedure for removing pro-inflammatory substances in non-neonatal paediatric patients with non-complex congenital heart disease. Additionally, we aimed to determine its effects on haemoconcentration and in lactate and fluid removal.MethodsA clinical trial was designed that included non-neonatal paediatric patients weighing >5kg with non-complex congenital heart disease and underwent surgery with cardiopulmonary bypass over a period of one year. They were randomised into a problem group (with modified ultrafiltration) and a control group (without it), and blood samples were taken in order to measure concentrations of interleukins (6 and 10), C3d and C4d complement fractions at the following times: baseline, before cardiopulmonary bypass, after it, after modified ultrafiltration, from the ultrafiltration concentrate, and on discharge from the operating room. Endpoints were defined in terms of morbidity and mortality, pro-inflammatory substances, lactate removal, fluid balance, and haemoconcentration.ResultsA total of 13 patients were included in the problem group and 15 in the control group. A significantly lower serum IL-6, IL-10, and lactate at the end of cardiopulmonary bypass, were observed in the problem group, as well as a greater fluid removal, lactate, and C4d concentration in the ultrafiltration product.ConclusionsModified ultrafiltration may benefit non-neonatal paediatric patients with congenital heart disease operated on with cardiopulmonary bypass, as it is able to decrease serum concentration of IL-6, IL-10, and lactate. Additionally, it can help to filter C4d and remove excess fluid, thus a greater haemoconcentration. Therefore, its routine use is recommended when the haemodynamic conditions are favourable

Nitazoxanide Exerts Immunomodulatory Effects on Peripheral Blood Mononuclear Cells from Type 2 Diabetes Patients

Background: Type 2 diabetes (T2D) is a low-grade inflammatory condition with abnormalities in the immune response mediated by T lymphocytes and macrophages. Drug repositioning for immunomodulatory molecules is an attractive proposal for treating T2D. Nitazoxanide (NTZ) is a broad-spectrum drug with promising immunomodulatory effects. Thus, we investigated the immunomodulatory effect of NTZ on peripheral blood mononuclear cells (PBMCs) from patients with T2D. Methods: Fifty patients with T2D were selected, and the proliferative response of T lymphocytes and the M1/M2 ratio of macrophages post cell culture were evaluated by flow cytometry, as well as measuring the concentration of cytokines by ELISA and the relative expression of microRNAs (miRNAs) related to the immune response by real-time PCR. Results: NTZ exerts an inhibitory effect on the cell proliferation of T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies without modifying cell viability, and significant decreases in the supernatant concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-10, and IL-12. Furthermore, NTZ negatively regulates the relative expression of miR-155-5p without changes in miR-146a-5p. The M1/M2 ratio of monocytes/macrophages decreased the M1 and increased the M2 subpopulation by NTZ. Conclusions: Our results suggest that NTZ exerts immunomodulatory effects on PBMCs from T2D patients, and shows potential alternative therapeutic benefits.</jats:p

Nitazoxanide Exerts Immunomodulatory Effects on Peripheral Blood Mononuclear Cells from Type 2 Diabetes Patients

Background: Type 2 diabetes (T2D) is a low-grade inflammatory condition with abnormalities in the immune response mediated by T lymphocytes and macrophages. Drug repositioning for immunomodulatory molecules is an attractive proposal for treating T2D. Nitazoxanide (NTZ) is a broad-spectrum drug with promising immunomodulatory effects. Thus, we investigated the immunomodulatory effect of NTZ on peripheral blood mononuclear cells (PBMCs) from patients with T2D. Methods: Fifty patients with T2D were selected, and the proliferative response of T lymphocytes and the M1/M2 ratio of macrophages post cell culture were evaluated by flow cytometry, as well as measuring the concentration of cytokines by ELISA and the relative expression of microRNAs (miRNAs) related to the immune response by real-time PCR. Results: NTZ exerts an inhibitory effect on the cell proliferation of T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies without modifying cell viability, and significant decreases in the supernatant concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-10, and IL-12. Furthermore, NTZ negatively regulates the relative expression of miR-155-5p without changes in miR-146a-5p. The M1/M2 ratio of monocytes/macrophages decreased the M1 and increased the M2 subpopulation by NTZ. Conclusions: Our results suggest that NTZ exerts immunomodulatory effects on PBMCs from T2D patients, and shows potential alternative therapeutic benefits

Table_1_Cytokine and microbiota profiles in obesity-related hypertension patients.docx

BackgroundSystemic arterial hypertension is linked to a heightened risk of cardiovascular diseases on a global scale. In Mexico, nearly half of adults in vulnerable conditions experience hypertension. Imbalance in the oral and intestinal microbiota composition has been observed in patients with hypertension, documented by a decrease of bacteria producing short-chain fatty acids, which play a critical role in blood pressure regulation.AimTo examine the cytokines’ profile and assess the characteristics of oral and gut microbiota in obesity-related hypertension in Mexican patients.MethodsA cross-sectional, observational, and analytical study was carried out. Twenty-two patients were categorized by their body mass index (BMI) as overweight and obese, and the diagnosis of primary hypertension. DNA from supragingival dental plaque and feces samples was used to carry out 16S rRNA sequencing. Additionally, 13 cytokines were quantified.ResultsIn the oral microbiota, Kluyvera was found to be significantly enriched in obese compared to overweight patients. Instead, the gut microbiota was dominated by Firmicutes. However, the correlation between certain genera and proinflammatory cytokines was noted.ConclusionThis exploratory study provides insights into the complex relationship between the oral and gut microbiota and their association with systemic inflammation in obesity-related hypertension.</p