JAK/STAT3 pathway promotes proliferation of ovarian aggregate-derived stem cells in vitro.

BACKGROUND: The accurate identification and isolation of ovarian stem cells from mammalian ovaries remain a major challenge because of the lack of specific surface markers and suitable in vitro culture systems. Optimized culture conditions for in vitro expansion of ovarian stem cells would allow for identifying requirements of these stem cells for proliferation and differentiation that would pave the way to uncover role of ovarian stem cells in ovarian pathophysiology. Here, we used three-dimensional (3D) aggregate culture system for enrichment of ovarian stem cells and named them aggregate-derived stem cells (ASCs). We hypothesized that mimicking the ovarian microenvironment in vitro by using an aggregate model of the ovary would provide a suitable niche for the isolation of ovarian stem cells from adult mouse and human ovaries and wanted to find out the main cellular pathway governing the proliferation of these stem cells. RESULTS: We showed that ovarian aggregates take an example from ovary microenvironment in terms of expression of ovarian markers, hormone secretion and supporting the viability of the cells. We found that aggregates-derived stem cells proliferate in vitro as long-term while remained expression of germline markers. These ovarian stem cells differentiated to oocyte like cells in vitro spontaneously. Transplantation of these stem cells in to chemotherapy mouse ovary could restore ovarian structure. RNA-sequencing analysis revealed that interleukin6 is upregulated pathway in ovarian aggregate-derived stem cells. Our data showed that JAK/Stat3 signaling pathway which is activated downstream of IL6 is critical for ovarian stem cells proliferation. CONCLUSIONS: We developed a platform that is highly reproducible for in vitro propagation of ovarian stem cells. Our study provides a primary insight into cellular pathway governing the proliferation of ovarian stem cells.

Identification of miR-20a as A Potential Discerning Biomarker for Non-Invasive versus Invasive Retinoblastoma.

OBJECTIVE: Intraocular retinoblastoma (RB) is common in kids. Although the cause of this disease is a mutation in the RB1 gene, the formed cancerous mass in different patients is seen in non-invasive states, limited to the ocular cavity or in invasive states distributed to other parts of the body. Because this tumor's aggressiveness cannot be predicted early, these patients receive systemic chemotherapy with multiple drugs. Treating non-invasive and invasive tumors separately reduces chemical drug side effects. The aim of this study was to identify diagnostic biomarkers by separating miRNAs in blood serum from invasive and non-invasive RB patients. MATERIALS AND METHODS: In this experimental study, selected three gene expression omnibus (GEO) datasets. Two were related to serum and tumor tissue miRNAs, and one was related to non-invasive and invasive RB gene expression. Examined RB gene-miRNA relationships. Then, we performed real-time polymerase chain reaction (PCR) on candidate miRNAs in the Y79 cell line and patient blood samples in non-invasive and invasive retinoblastoma. RESULTS: Fourteen high-expression and 7 low-expression miRNAs resulted. MiR-181, miR-135a, miR-20a, miR-373, and miR-191 were common genes with differential genes between invasive and non-invasive retinoblastoma. Only MiR-181 was upregulated in the Y79 RB cell line. Other candidate miRNAs expressed less. Invasive retinoblastomas increased serum miR-20a and miR-191. CONCLUSION: Integrated and regular bioinformatics analyses found important miRNAs in patients' and miR-20a, miR- 191, and miR-135a can distinguish non-invasive and invasive retinoblastoma, suggesting further research.

Serum uric acid to high-density lipoprotein ratio as a novel indicator of inflammation is correlated with the presence and severity of metabolic syndrome: A large-scale study.

INTRODUCTION: We investigated the association of serum uric acid to high-density lipoprotein ratio (UHR) with the presence and severity of metabolic syndrome (MetS) among MASHAD cohort participants. METHODS: In this cross-sectional study, according to International Diabetes Federation criteria, the cohort participants were divided into MetS (+) and MetS (-) groups. MetS (+) were classified into Group 1 (those with 3 MetS criteria), Group 2 (those with 4 MetS criteria) and Group 3 (those with 5 MetS criteria). UHR was compared among the groups. RESULTS: Data related to 9637 subjects including 3824 MetS (+) and 5813 MetS (-) were analysed. The mean UHR was significantly higher (p < .001) in the MetS (+) group compared with the MetS (-) group. UHR increased as the MetS severity increased (p < .001). ROC analysis revealed that UHR greater than 9.5% has 89.07% sensitivity and 77.03% specificity in differentiating MetS (-) from MetS (+) subjects. CONCLUSION: Among MASHAD cohort study participants, a significant association between UHR and MetS was found. Furthermore, there is an increase in UHR as the severity of MetS increases. Registration number of MASHAD cohort study: 85134.