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Aviwe Ntsethe, Irene Mackraj Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South AfricaCorrespondence: Irene Mackraj; Aviwe Ntsethe, Department of Human Physiology, University of KwaZulu-Natal, Durban, South Africa, Tel +27 31-260-7770 ; +27 31-260-7192, Email mackraji@ukzn.ac.za; Ntsethea@ukzn.ac.zaIntroduction: Hypertensive disorders of pregnancy are characterized by widespread maternal endothelial dysfunction. Elevated secretion of exosomes has been associated with endothelial dysfunction. Exosomes play a role in cell–cell communication by transferring microRNAs. These microRNAs are associated with the pathogenesis of hypertensive disorders of pregnancy through the regulation of endothelial function. This study characterizes exosomes and determines exosomal miR-155 and miR-222 expression levels in women with gestational hypertension (GH) and preeclampsia (PE).Methods: Exosomes were isolated and thereafter characterised using NTA, microscopy and ELISA. Results: Exosomes were elevated in the serum of pregnant women with GH and PE (P< 0.05). The circulating exosomes and placental exosomes were increased in both GH and PE (P< 0.0001). The exosomal miR-155 increased in PE but not in GH (P < 0.05). MiR-222 decreased in PE (P < 0.05).Discussion: Elevated exosomes in pregnant women with GH and PE may be indicative of exosomes being potential biomarkers for both GH and PE. The difference in the exosomal miR-155 and miR-222 expression in PE and GH suggested that these two disorders have different pathological pathways.Keywords: exosomes, gestational hypertension, MiR-155, MiR-222, preeclampsia

Salman Sadeghzadeh,1 Mahmood Dehghani Ashkezari,1 Seyed Morteza Seifati,1 Mohammad Yahya Vahidi Mehrjardi,2,3 Masoud Dehghan Tezerjani,4 Sara Sadeghzadeh,5 Seyed Amir Behtash Ladan1 1Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran; 2Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 3Department of Genetics, Medical School, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 4Abortion Research Center, Yazd Institute of Reproductive Sciences, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 5Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, IranCorrespondence: Mahmood Dehghani AshkezariMedical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, IranEmail mdashkezary@gmail.comBackground: In recent years, considerable attention has been paid to the role of microRNAs (miRs) as biomarkers in type 2 diabetes (T2D). The aim of the study was to evaluate the expression levels of miR-15a and miR-222 in diabetic, pre-diabetic, and healthy individuals.Materials and Methods: Ninety individuals, who were referred to the Yazd diabetic center, were enrolled in this study and then classified into three groups as healthy, pre-T2D, and diabetic based on the clinical manifestations. Real-time PCR was performed to explore miRs expression in the plasma samples of the studied population. The correlation between the biochemical characteristic and the expression of these miRs as well as specificity and sensitivity of different clinical markers in healthy and pre-diabetic groups was evaluated.Results: miR-222 expression was significantly upregulated in the pre-T2D cases compared to the control subjects (P< 0.001), while no significant difference was found between the pre-T2D and T2D groups (P< 0.05). The expression of miR-15a was statistically downregulated in the pre-T2D and T2D subjects (P< 0.05). The receiver operating characteristic (ROC) curve analysis of miR-15a expression with a cutoff point of 1.12 resulted in the area under the curve (AUC) of 85% (95% CI 0.865– 0.912; P< 0.001) with 84% and 85% sensitivity and specificity, respectively. Similarly, for miR-222, the cutoff point of 4.03 and AUC of 86% (95% CI 0.875– 0.943; P< 0.001) discriminated against the pre-T2D and control subjects via the sensitivity and specificity of 86% and 87%, respectively. Moreover, miR-15a values showed a negative correlation with FG (R=− 0.32, P=0.005); however, miR-222 values were positively correlated with FG (R=0.25, P=0.03) in the pre-T2D group. Furthermore, miR-222 values were correlated with OGTT in the pre-T2D group (R=0.27, P=0.001). In addition, LDL-C had a negative correlation with miR-222 values in the pre-T2D group (R=− 0.23, P=0.02).Conclusion: This study indicated that the plasma expression levels of miR-222 and miR-15a can be considered as non-invasive, fast tools to separate the pre-T2D individuals from their healthy counterparts. Accordingly, this information could be used to predict the development of the disease as well as a direction for optimal therapy, thus refining outcomes in patients with diabetes.Keywords: type 2 diabetes, miR-15a, miR-222, biomarker, gene expression

Purpose: To determine the role and underlying mechanism of hepsin in epithelial-mesenchymal transition (EMT) and cell invasion in prostate cancer., Methods: The expression of hepsin in prostate cancer tissue samples and cell lines was measured by immunohistochemical staining and Western blotting. The EMT and cell invasion abilities of prostate cancer cells were detected by Western blot and transwell assays. RNA transfection was used to inhibit or overexpress related genes. The expression of miR-222 was detected by RT-qPCR. A dual‑luciferase reporter gene assay was performed to determine the target of miR-222., Results: Hepsin expression was upregulated in prostate cancer tissue samples and cell lines. Inhibition of hepsin attenuated EMT and cell invasion and downregulated the expression of miR-222. Decreased miR-222 expression enhanced the level of PPP2R2A, which in turn attenuated the AKT signaling. Activation of miR-222 or AKT could block the inhibitory effects on EMT and cell invasion induced by hepsin deficiency., Conclusion: Hepsin promotes EMT and cell invasion through the miR-222/PPP2R2A/AKT axis in prostate cancer., Competing Interests: The authors declare that they have no competing interests., (© 2020 Li et al.)

Background: MicroRNAs (miRNAs) are important diagnostic and prognostic markers in cancer. In the study reported here, we analyzed the potential relationship between miRNA expression and extrathyroidal invasion in papillary thyroid carcinoma (PTC)., Methods: Samples from 91 patients with PTC were collected from January 2008 to April 2012 at our hospital. To detect the levels of miRNA expression in fresh frozen tissues from patients with extrathyroidal invasion (n = 3) and non-extrathyroidal invasion (n = 3), miRNA array was carried out. The upregulated miRNAs between the two groups were confirmed by using real-time reverse transcriptase polymerase chain reaction., Results: The levels of miR-146b, miR-221, miR-222, and miR-135b were significantly higher in the extrathyroidal invasion group than in the non-extrathyroidal invasion group (P = 0.001, 0.019, 0.004, and 0.006, respectively). In addition, the miR-146b expression level was significantly higher in the massive extrathyroidal invasion group than in the minimal extrathyroidal invasion group (P = 0.016). The expression levels of miR-146b, miR-222, and miR-135b were significantly associated with tumor size (P = 0.018, 0.008, and 0.024, respectively). The upregulation of miR-146b and miR-222 was significantly associated with higher tumor-node-metastasis stage (P = 0.004 and 0.0001, respectively). The expression level of miR-222 was also correlated with age and sex (P = 0.048 and 0.002, respectively)., Conclusion: Our results reveal that the expression of four miRNAs correlated with extrathyroidal invasion and other clinicopathologic features in PTCs, which may support their potential clinical value as prognostic biomarkers for PTCs.