Abstract. miRNAs are small, non-coding RNAs that play important roles in various biological processes. The aims of our study were to investigate whether cell-free miRNAs can be measured in urine samples and might be an accurate biomarker of bladder cancer. Datasets of GSE20418 and GSE19717 were used for analysis, and two miRNAs, miR-145 and miR-200a, were selected for study. A total of 207 patients with primary transitional cell carcinoma of the urinary bladder and 144 healthy normal controls were enrolled. Using quantitative PCR, the levels of miR-145 and miR-200a in urine were measured and compared with the clinicopathological features of bladder cancer. According to our experiments, cell-free miRNAs were present in urine and were stable. Assessment of miR-145 levels was able to distinguish bladder cancer patients from non-cancer controls (77.8% sensitivity and 61.1% specificity for NMIBC, AUC 0.729; 84.1 and 61.1% for MIBC, respectively, AUC 0.790) and showed good correlation with grade (p=0.048). In addition, miR-200a was shown to be an independent predictor of NMIBC recurrence by multivariate analysis (OR 0.449, p=0.013). A higher risk of recurrence was observed among patients with a lower miR-200a level compared to patients with higher miR-200a levels (log-rank test, p=0.040). Urinary cell-free miRNAs show promise as noninvasive biomarkers for diagnosis and recurrence of bladder cancer. IntroductionSurveillance strategies for bladder cancer recurrence have historically relied on the diagnostic combination of cystoscopy and urinary cytology. However, the cystoscopic approach is costly, invasive and uncomfortable. Urinary cytology is a preferable technique for the diagnosis of bladder tumors because of its high specificity; however, it has low sensitivity. For these reasons, many new urine-based tests for urinary bladder cancer have been developed, and screens for bladder tumor antigen (BTA), nuclear matrix protein 22 (NMP22), urine fibrin fibrinogen degradation products (FDP), ImmunoCyt and FISH (UroVysion) have all been approved for clinical use (1,2). However, the specificities of these new urine markers are low in comparison with urinary cytology, although they have higher sensitivities. Thus, none of the currently identified urine markers can replace cystoscopy or urinary cytology (3). miRNAs are small, nonprotein-coding RNA regulators involved in numerous biological and developmental processes (4,5). Cumulative evidence suggests that the dysregulation of miRNA plays an important role in many human disorders, including cancer. Approximately 50% of human miRNAs are encoded in genomic regions that are frequently altered in cancer (6-8). Recently, miRNAs have emerged as highly tissue-specific biomarkers with potential clinical applicability, not only as diagnostic markers but also as prognostic predictors for numerous cancers.Numerous recent studies have explored circulating cell-free miRNAs and provided evidence that miRNAs exist in a stable form in various body fluids, such as blood, urine, saliva, and p...

Atmospheric (in vitro) oxygen pressure is around 150 mm Hg (20% O 2 ), whereas physiologic (in vivo) oxygen pressure ranges between 5 and 50 mm Hg (0.7-7% O 2 ). The normoxic environment in cell culture does not refer to a physiological stem cell niche. The aim of this study is to investigate the effect of oxygen concentration on cell properties of human mesenchymal stem cells (MSCs). We analyzed cell proliferation rate, senescence, immunophenotype, stemness gene expression and differentiation potency with human urine stem cells (USCs), dental pulp stem cells (DPSCs), amniotic fluid stem cells (AFSCs), and bone marrow stromal cells (BMSCs). USCs, DPSCs, AFSCs and BMSCs were cultured under either 5% O 2 hypoxic or 20% O 2 normoxic conditions for 5 days. MSCs cultured under hypoxia showed significantly increased proliferation rate and high percentage of S-phase cells, compared to normoxic condition. In real-time PCR assay, the cells cultured under hypoxia expressed higher level of Oct4, C-Myc, Nanog, Nestin and HIF-1a. In immunophenotype analysis, MSCs cultured under hypoxia maintained higher level of the MSC surface markers, and lower hematopoietic markers. Senescence was inhibited under hypoxia. Hypoxia enhances osteogenic differentiation efficiency compared to normoxia. Hypoxia showed enhanced cell proliferation rate, retention of stem cell properties, inhibition of senescence, and increased differentiation ability compared to normoxia.

Objective: To describe and visually depict laryngeal complications in patients recovering from coronavirus disease 2019 (COVID-19) infection along with associated patient characteristics.

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