Reduced kinase function in two ultra-rare TNNI3K variants in families with congenital junctional ectopic tachycardia.

Genetic missense variants in TNNI3K, encoding troponin-I interacting kinase, have been associated with dilated cardiomyopathy (DCM) and observed in families with supraventricular tachycardias (SVT). Previously, a family harboring the TNNI3K-c.1615A > G (p.Thr539Ala) variant presented with congenital junctional ectopic tachycardia (CJET), an arrhythmia that arises from the atrioventricular (AV) node and His bundle. However, this was a relatively small four-generational family with limited genetic testing (N = 3). We here describe a multigenerational family with CJET harboring a novel ultra-rare TNNI3K variant: TNNI3K-c.1729C > T (p.Leu577Phe). Of all 18 variant carriers, 13 individuals presented with CJET, resulting in a genetic penetrance of 72%. In addition, CJET is reported in another small family harboring TNNI3K-c.2225C > T (p.Pro742Leu). Similar to the previously published CJET family, both TNNI3K variants demonstrate a substantial reduction of kinase activity. Our study contributes novel evidence supporting the involvement of TNNI3K genetic variants as significant contributors to CJET, shedding light on potential mechanisms underlying this cardiac arrhythmia.

Circulating Exosomal miRNAs as Biomarkers for the Diagnosis and Prognosis of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors in the gastrointestinal tract. It is a multifactorial disease that involves environmental factors, genetic factors, and lifestyle factors. Due to the absence of specific and sensitive biomarkers, CRC patients are usually diagnosed at an advanced stage and consequently suffer from a low 5-year overall survival rate. Despite improvements in surgical resection and adjuvant chemotherapy, the prognosis of patients with CRC remains unfavorable due to local and distant metastases. Several studies have shown that small noncoding RNAs, such as microRNAs packed in exosomes, are potential biomarkers in various types of cancers, including CRC, and that they can be detected in a stable form in both serum and plasma. In this review, we report the potential of circulating exosomal miRNAs to act as biomarkers for the diagnosis and prognosis of CRC.

Relationship Between Metabolic Syndrome and the Brazilian Workers' Food Program in Male and Female Manufacturing Workers.

INTRODUCTION: Several studies have reported increased cardiometabolic risk among workers assisted by food assistance public policies. The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) and its individual components among manufacturing workers and their relationship to the Brazilian Workers' Food Program (WFP). METHODS: It was a prospective, cross-sectional, two-stage survey comparative of manufacturing workers from companies adherent and non-adherent to the WFP stratified by sector of activity and company size. The workers were interviewed in the workplace, and data on waist circumference (WC), blood pressure, and 12-hours fasting blood glucose (FBG), serum triglycerides (TG), and total and HDL-cholesterol were obtained. Mixed effects multilevel regression was used to compare WFP and non-WFP groups separately in each sex. All subjects gave written informed consent. RESULTS: The survey included 332 workers from 16 WFP companies and 344 workers from 17 non-WFP companies. The general prevalence of MetS, according to IDF/AHA/NHLBI criteria, was high but not statistically different between sexes (39.8% in females versus 28.5% for males, p=0.16). Statistically significant differences were found between sexes in the prevalence of individual components: WC (77.8% in females versus 38.3% in males, p=0.002), TG (27.3% in females versus 40.8% in males, p=0.07), and HDL-C (52.2% in females versus 43.1% in males, p=0.05). Among males, MetS prevalence was significantly higher in the WFP group (33.0% versus 23.9%, p=0.008), and, in the individual components, the WFP group had higher prevalence of increased WC (47.0% versus 29.4%, p<0.001) and elevated FBG (8.9% versus 6.3%, p<0.001), as well as greater average levels of TG, HDL-C and FBG. Among female workers, no statistically significant differences between groups were observed in MetS prevalence and its individual components, but WFP female worker presented lower systolic and diastolic blood pressure. CONCLUSION: In a low-income population, male manufacturing workers participating in a food assistance program are at increased risk of MetS, an effect that was not identified among female workers.

Identification of new genes associated to senescent and tumorigenic phenotypes in mesenchymal stem cells.

Although human mesenchymal stem cells (hMSCs) are a powerful tool for cell therapy, prolonged culture times result in replicative senescence or acquisition of tumorigenic features. To identify a molecular signature for senescence, we compared the transcriptome of senescent and young hMSCs with normal karyotype (hMSCs/n) and with a constitutional inversion of chromosome 3 (hMSC/inv). Senescent and young cells from both lineages showed differentially expressed genes (DEGs), with higher levels in senescent hMSCs/inv. Among the 30 DEGs in senescent hMSC/inv, 11 are new candidates for biomarkers of cellular senescence. The functional categories most represented in senescent hMSCs were related to cellular development, cell growth/proliferation, cell death, cell signaling/interaction, and cell movement. Mapping of DEGs onto biological networks revealed matrix metalloproteinase-1, thrombospondin 1, and epidermal growth factor acting as topological bottlenecks. In the comparison between senescent hMSCs/n and senescent hMSCs/inv, other functional annotations such as segregation of chromosomes, mitotic spindle formation, and mitosis and proliferation of tumor lines were most represented. We found that many genes categorized into functional annotations related to tumors in both comparisons, with relation to tumors being highest in senescent hMSCs/inv. The data presented here improves our understanding of the molecular mechanisms underlying the onset of cellular senescence as well as tumorigenesis.