Circulating miR-146a as a possible candidate biomarker in the indeterminate phase of Chagas disease

BACKGROUND: Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. Micro-RNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-ß signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction. RESULTS: Overexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated. CONCLUSIONS: The expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease.

Effect of fresh frozen plasma on the in vitro activation of U937 monocytes: a potential role for the age of blood donors and their underlying cytokine profile

BACKGROUND: Fresh frozen plasma (FFP) administration may increase the risk of nosocomial infections in parallel with the development of immune modulation. This could be driven by soluble mediators, possibly influencing the in vitro activation of human U937 monocyte cells, in a manner dependent on the age of the donors. METHODS: FFP donors were stratified into groups of 19-30 years, 31-40 years or 41-50 years, and U937 cells were cultured with FFP (alone or plus lipopolysaccharide-LPS) for 24 h. Both in FFP and supernatants, TNF, IL-1ß, IL-6, and IL-10 levels were measured by ELISA. Additionally, CD11B, TLR2, and CASP3 gene expression were measured by qtPCR in U937 cells. Total phagocytic activity was also assayed. RESULTS: Elevated IL-10, but low TNF and IL-1ß levels were measured in FFP from individuals aged 19-40 years, whereas in individuals aged 41-50 years FFP were characterized by equalized TNF and IL-10 levels. Elevated IL-6 levels were found in all FFP samples, especially in those from the oldest individuals. FFP stimulation was associated with striking modifications in cytokine production in an age-dependent way. Exposure to FFP attenuates the response to LPS. TLR2 and CD11B expression were enhanced regardless of the age of plasma donors, although CASP3 expression was increased only when FFP from individuals aged 19-40 years were tested. Phagocytosis decreased after exposure to FFP regardless of donor age. CONCLUSION: Our results suggest that soluble mediators in FFP may modulate the functioning of monocytes. Interestingly, this effect appears to be partially influenced by the age of donors.

Omentina: papel en la resistencia a la insulina, inflamación y protección cardiovascular / Omentin: Role in insulin resistance, inflammation and cardiovascular protection

La omentina es una nueva adipocina a la que se le ha atribuido la capacidad de regular actividades metabólicas (sensibilidad a la insulina) y antiinflamatorias, ofreciendo protección cardiovascular en la obesidad y diabetes mellitus tipo 2. Por lo anterior, es importante conocer los mecanismos a través de los cuales confiere protección cardiovascular, con el objetivo de considerar la omentina como blanco o agente terapéutico en este escenario.

The omentin is an adipokine, which role is due to the capacity of regulate metabolic (insulin sensitivity) and anti-inflammatory activities, thus conferring vascular protection during obesity and diabetes mellitus type 2. By this, it is important to know the mechanisms by which omentin confers cardiovascular protection, with the purpose of establish omentin a possible therapeutic target or molecule on this scenario.

Adipocinas, tejido adiposo y su relación con células del sistema inmune / Adipocytokines, adipose tissue and its relationship with immune system cells

Adipocinas o adipocitocinas son los términos para referirse a las proteínas secretadas por el tejido adiposo. Entre ellas destacan la pro teína estimuladora de acilación (ASP), TNF-a, IL-6, la resistina, la leptina y la adiponectina, con influencia sobre la sensibilidad a la insulina, así como el angiotensinógeno y el inhibidor del activador de plasminógeno (PAI-1) que tienen efecto sobre la vascularización. Diversos estudios indican que existe relación entre los adipocitos y las células del sistema inmune, consecuencia de un mecanismo de supervivencia y adaptación metabólica bajo condiciones adversas. Ahora se sabe que las adipocinas contribuyen a la inflamación y la resistencia a la insulina que presenta el sujeto obeso. Estas adaptaciones, conjuntamente con el estrés y el confort de la vida moderna, han contribuido al deterioro del organismo y han desencadenado la inflamación originada en el tejido adiposo. El objetivo de esta revisión es analizar la información que ha llevado al descubrimiento y esclarecimiento de la fisiología del tejido adiposo en relación con la secreción de diversas proteínas y de la inflamación originada en el mismo. En este sentido, las terapias dirigidas al tratamiento de las enfermedades relacionadas con la obesidad deberán orientarse a modificar el proceso inflamatorio originado en el tejido adiposo.

A dipokines or adipocytokines are the proteins secreted by the adipose tissue. These bioactive molecules include proteins that modify insulin sensitivity (acylation stimulating protein (ASP), TNF-a, IL- 6, resistin, leptin and adiponectin), and proteins that have known effects on vascularity (angiotensinogen and the plasminogen inhibitor protein PAI-1). Several studies have found a close relationship between adipocytes and immune cells as a consequence of evolutionary mechanisms that favor metabolic adaptation and survival under adverse conditions. It is known that adipokines contribute to the inflammation and insulin resistance present in obese individuals. The aim of this review is to analyze current information related to the physiology of the adipose tissue, with a special emphasis on the secretion of adipokines and their role in inflammation. We recommend that therapies addressing the treatment of obesity related disorders should focus on modifying the inflammatory process that originates in the adipose tissue.