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1.
Aging Cell ; 20(7): e13383, 2021 07.
Article in English | MEDLINE | ID: mdl-34092006

ABSTRACT

Aging is the main risk factor for cardiovascular diseases. In humans, cardiac aging remains poorly characterized. Most studies are based on chronological age (CA) and disregard biological age (BA), the actual physiological age (result of the aging rate on the organ structure and function), thus yielding potentially imperfect outcomes. Deciphering the molecular basis of ventricular aging, especially by BA, could lead to major progresses in cardiac research. We aim to describe the transcriptome dynamics of the aging left ventricle (LV) in humans according to both CA and BA and characterize the contribution of microRNAs, key transcriptional regulators. BA is measured using two CA-associated transcriptional markers: CDKN2A expression, a cell senescence marker, and apparent age (AppAge), a highly complex transcriptional index. Bioinformatics analysis of 132 LV samples shows that CDKN2A expression and AppAge represent transcriptomic changes better than CA. Both BA markers are biologically validated in relation to an aging phenotype associated with heart dysfunction, the amount of cardiac fibrosis. BA-based analyses uncover depleted cardiac-specific processes, among other relevant functions, that are undetected by CA. Twenty BA-related microRNAs are identified, and two of them highly heart-enriched that are present in plasma. We describe a microRNA-gene regulatory network related to cardiac processes that are partially validated in vitro and in LV samples from living donors. We prove the higher sensitivity of BA over CA to explain transcriptomic changes in the aging myocardium and report novel molecular insights into human LV biological aging. Our results can find application in future therapeutic and biomarker research.


Subject(s)
Aging/genetics , Biomarkers/metabolism , Heart Ventricles/metabolism , MicroRNAs/genetics , Female , Humans , Male
7.
Anal Quant Cytopathol Histpathol ; 36(1): 9-14, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24902366

ABSTRACT

OBJECTIVE: To describe the usefulness of endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNAC) in pancreatic lesions. STUDY DESIGN: During a 5-year period (2007-2011) a total of 391 patients with pancreatic lesions have been studied using EUS-FNAC, with 43 of them having cytohistological correlation with core biopsy or surgical specimens. The diagnostic performance of this technique with and without the pathologist in the endoscopy room has been compared. RESULTS: On the cytological smears, adenocarcinoma was diagnosed in 13 (30.2%) cases and neuroendocrine neoplasm in 2 (4.6%). Six (13.9%) cases were considered suspicious for malignancy, 2 (4.6%) were solid pseudopapillary tumors, and 20 (46.5%) were negative. There were no mucin-producing cystic neoplasms in the cytological diagnostic approach. After the cytohistological correlation, 23 (53.5%) cases were true positive, 11 (25.5%) were true negative, and 9 (21%) were false negative. There were no false positive cases in the series. Diagnostic precision was 79%, sensitivity 71.18%, specificity 100%, positive predictive value 100%, and negative predictive value 55%. The diagnostic performance of this technique is significantly higher (p < 0.015) when the pathologist is present in the endoscopy room. CONCLUSION: Our data support the usefulness and reliability of EUS-FNAC in the diagnosis of pancreatic lesions. In our experience, significantly better results are obtained when the pathologist takes an active part in the procedure.


Subject(s)
Adenocarcinoma/pathology , Carcinoma, Neuroendocrine/pathology , Endosonography/methods , Endosonography/standards , Pancreatic Neoplasms/pathology , Biopsy, Fine-Needle/methods , Biopsy, Fine-Needle/standards , False Negative Reactions , Humans , Pathology, Clinical , Physicians , Reproducibility of Results , Sensitivity and Specificity
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