Peripheral Blood miRome Identified miR-155 as Potential Biomarker of MetS and Cardiometabolic Risk in Obese Patients.

This study explored circulating miRNAs and target genes associated with metabolic syndrome (MetS) and cardiometabolic risk in obese patients. Small-RNA sequencing was used to assess the peripheral blood miRNome of 12 obese subjects (6 MetS and 6 non-MetS). Differentially expressed miRNAs and target genes were further analyzed by qPCR in a larger sample of obese patients (48 MetS and 32 non-MetS). miRNA:mRNA interactions were studied using in silico tools. miRNome analysis identified 10 downregulated miRNAs in MetS compared to non-Met patients (p < 0.05). In silico studies revealed three miRNAs (miR-155, miR-181a, and let-7a) and their predictive targets (CCAAT/enhancer-binding protein beta-CEBPB, KRAS proto-oncogene, GTPase-KRAS and suppressor of cytokine signaling 1-SOCS1) with a potential role in the insulin receptor signaling pathway. miR-155 expression was reduced and CEBPB mRNA levels were increased in MetS patients (p < 0.05), and these effects were correlated with the number of MetS diagnostic criteria (p < 0.05). Increased HOMA-IR (>7.6) was associated with low miR-155 levels, high CEBPB expression, and serum hsCRP (p < 0.05). miR-155 was negatively correlated with CEBPB, HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin (p < 0.05). Downregulation of circulating miR-155 is associated with insulin resistance, poor glycemic control, and increased MetS-related cardiometabolic risk, and these effects are potentially mediated by interaction with CEBPB.

Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP.

Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4+FoxP3- T cells expressing Helios (FoxP3-Helios+) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4+Helios+ T cells regardless of FoxP3 expression (FoxP3+/-Helios+). We show that CD4+GARP+/-LAP+ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3+Helios+ Tregs proliferate in vitro significantly less than FoxP3+Helios- Tregs upon TCR stimulation. Unlike FoxP3+Helios- Tregs, FoxP3+Helios+ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3+Helios+ Tregs have more suppressive characteristics, compared with FoxP3+Helios- Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3+Helios+ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction.

Valor diagnóstico de la procalcitonina, la interleucina 8, la interleucina 6 y la proteína C reactiva en la detección de bacteriemia y fungemia en pacientes con cáncer / Diagnostic value of procalcitonin, interleukin 8, interleukin 6, and c-reactive protein for detecting bacteremia and fungemia in cancer patients

Introducción y objetivo La bacteriemia es una de las causas más importantes de morbimortalidad en los pacientes con cáncer. El objetivo del presente estudio es evaluar la utilidad diagnóstica de la procalcitonina (PCT), la interleucina 8 (IL-8), la interleucina 6 (IL-6) y la proteína C reactiva (PCR) en la detección de bacteriemia en pacientes con cáncer. Pacientes y métodos Se midieron los valores de PCT, IL-8, IL-6 y PCR en 2 grupos de pacientes con cáncer que presentaron fiebre: el grupo con bacteriemia verdadera y el grupo sin bacteriemia. Resultados Se estudiaron 79 síndromes febriles en 79 pacientes, 43 hombres y 36 mujeres. Cuarenta y cuatro pacientes pertenecían al grupo de bacteriemia verdadera. Se encontraron diferencias significativas al comparar los valores de PCT, IL-8 e IL-6 (p<0,001, p<0,001, p=0,002, respectivamente) entre los pacientes con bacteriemia verdadera y sin bacteriemia. Los resultados de la PCR no mostraron diferencias significativas entre los 2 grupos estudiados (p=0,23). El punto de corte para la PCT fue de 0,5ng/ml y mostró la mejor especificidad (91,4%), con una sensibilidad del 59,1%.ConclusionesEl marcador de infección que puede aportar más información en el diagnóstico de bacteriemia en pacientes con cáncer es la PCT (AU)

Background and Objective Bacteremia is one of the most important causes of morbidity and mortality in cancer patients. The aim of this study was to evaluate the diagnostic usefulness of procalcitonin (PCT), interleukin 8 (IL-8), interleukin 6 (IL-6), and C-reactive protein (CRP) in the detection of bacteremia in cancer patients. Patients and methods PCT, IL-8, IL-6, and CPR levels were measured in 2 groups of cancer patients who had fever: one group with true bacteremia and another without bacteremia. Results Seventy-nine febrile episodes were analyzed in 79 patients, 43 men and 36 women. Forty-four patients were in the true bacteremia group. Significant differences in PCT (P<0.001), IL-8 (P<0.001), and IL-6 (P=0.002) values were found between patients with and without true bacteremia. CPR results were not significantly different between the groups (P=0.23). The cut-off point for PCT was 0.5ng/mL and this parameter yielded the best specificity at 91.4%, with a sensitivity of 59.1%.ConclusionsAmong the infection markers studied, PCT provided the most information for diagnosing bacteremia in cancer patients (AU)