Circular RNAs in stem cells: from basic research to clinical implications.

Circular RNAs (circRNAs) are a special class of endogenous RNAs with a wide variety of pathophysiological functions via diverse mechanisms, including transcription, microRNA (miRNA) sponge, protein sponge/decoy, and translation. Stem cells are pluripotent cells with unique properties of self-renewal and differentiation. Dysregulated circRNAs identified in various stem cell types can affect stem cell self-renewal and differentiation potential by manipulating stemness. However, the emerging roles of circRNAs in stem cells remain largely unknown. This review summarizes the major functions and mechanisms of action of circRNAs in stem cell biology and disease progression. We also highlight circRNA-mediated common pathways in diverse stem cell types and discuss their diagnostic significance with respect to stem cell-based therapy.

Overexpression of erythropoietin-producing hepatocyte receptor B4 and ephrin-B2 is associated with estrogen receptor expression in endometrial adenocarcinoma.

Endometrial adenocarcinoma (EC) is one of the most frequently diagnosed types of endometrial cancer and is typically a consequence of continuous estrogen receptor stimulation. Erythropoietin-producing hepatocyte receptor B4 (EphB4) and its ligand ephrin-B2 have been reported to be overexpressed in EC cells; however, the function in EC remains unclear. The present study aimed to elucidate the role of EphB4 and ephrin-B2 in EC. The protein expression pattern of EphB4 and ephrin-B2 was analyzed through immunohistochemistry and western blot analysis in endometrium with adenomyosis or simple endometrial hyperplasia, atypical endometrial hyperplasia, double-positive estrogen receptor (ER)/progesterone receptor (PR) EC and double-negative ER/PR EC. The expression of EphB4 and ephrin-B2 was demonstrated to be increased in atypical EH and ER/PR-positive EC, but not ER/PR-negative EC. Furthermore, EphB4 and ephrin-B2 expression was positively associated with ER expression in EC tissue. The results of the present study suggest that the overexpression of EphB4 and ephrin-B2 in the endometrium serves a role in the pathogenesis of EC, in addition to being associated with ER expression.

Short hairpin ribonucleic acid constructs targeting insulin-like growth factor binding protein-3 rehabilitated decreased testosterone concentrations in diabetic rats.

BACKGROUND: The aim of this study was to determine if shRNA constructs targeting insulin-like growth factor binding protein-3 can rehabilitate decreased serum testosterone concentrations in streptozotocin-induced diabetic rats. MATERIAL/METHODS: After 12 weeks of intracavernous administration of IGFBP-3 shRNA, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 at mRNA and protein levels was detected by quantitative real-time PCR analysis and Western blot, respectively. The concentrations of serum testosterone and cavernous cyclic guanosine monophosphate were detected by enzyme-linked immunosorbent assay. RESULTS: After 12 weeks of intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic control group (p<0.01). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. Both serum testosterone and cavernous cyclic guanosine monophosphate concentrations were significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic control group (p<0.01). CONCLUSIONS: These results suggest that IGFBP-3 shRNA may rehabilitate erectile function via increases of concentrations of serum testosterone and cavernous cyclic guanosine monophosphate in streptozotocin-induced diabetic rats.

[Evaluation of the clinical value of simultaneous hysterectomy and bilateral salpingectomy in perimenopausal women].

OBJECTIVE: To investigate the effects on pelvic pseudocyst, ovarian function and symptoms of peri-menopausal period in patients with benign uterine disease undergoing simultaneous hysterectomy and bilateral salpingectomy. METHODS: From Jan. 2000 to Dec. 2006, 1193 patients with benign uterine disease underwent total or subtotal hysterectomy, they were followed up for 48 months, 334 patients lost follow-up, the other 859 patients were divided into 2 groups, including 348 patients undergoing simultaneous hysterectomy and bilateral salpingectomy in study group and 511 patients undergoing only hysterectomy in control group. The occurrence of pelvic pseudocyst and symptoms of peri-menopausal period and the changes of serum sexual hormone were observed. RESULTS: (1) The rate of pelvic pseudocyst was 1.7% (6/348) in study group, which was significantly lower than 4.3% (22/511) in control group (P = 0.036). (2) There was an increasing trend of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and a decreasing trend of estradiol (E(2)) at range of 6 - 48 months after surgery. At 3 months after surgery, LH in study group was significantly higher than that in control group [(13.9 ± 2.2) U/L vs. (12.6 ± 2.5) U/L, P = 0.032]; FSH in study group at 6 months and 12 months after surgery were (17.6 ± 2.2) U/L and (26.7 ± 5.0) U/L, which were significantly higher than (16.2 ± 2.8) U/L and (24.3 ± 3.1) U/L in control group (P = 0.035 and P = 0.031). At 12 months after surgery, LH in study group of (24.1 ± 3.0) U/L was significantly higher than (22.5 ± 1.8) U/L in control group (P = 0.017). E(2) in control group of (97 ± 22) pmol/L was significantly lower than (109 ± 17) pmol/L in control group at 24 months after surgery (P = 0.028); FSH in study group was lower than that in control group at 48 months after surgery [(34.9 ± 6.7) U/L vs. (38.0 ± 4.8) U/L, P = 0.043]. There were no significant differences of FSH, LH, and E(2) between two groups at the other time points (P > 0.05). (3) At 6 months after surgery, the rate of perimenopausl systems of 21.8% (76/348) in study group was significantly higher than 15.9% (81/511) in control group (P = 0.026). However, at 24 months after surgery, the rate of perimenopausal symptoms of 54.4% (278/511) in control group was significantly higher than 47.1% (164/348) in study group (P = 0.036). CONCLUSION: Simultaneous hysterectomy and bilateral salpingectomy could decrease the occurrence of pelvic pseudocyst, and had similar effects on ovarian function and peri-menopausal symptoms compared with only hysterectomy in patients with benign uterine diseases.

Flap removal or flap preservation during LASEK surgery.

The objective of this study was to evaluate the effectiveness of corneal epithelial flap removal or flap preservation during LASEK operation on myopia and to determine whether there was any accrual of benefit in either approach. From March 2006 to March 2008, some 582 patients (1,164 eyes) who presented with myopia and myopic astigmatism were treated with corrective LASEK operations. They were divided into two groups: one group underwent corneal flap-preservation while the other had the corneal flap removed. Each group comprised 582 eyes, and the data accumulated were retrospectively analyzed. Each patient was examined after 1, 3, 5, and 7 days; 2 weeks; and 1, 2, 3, 6, and 12 months after LASEK surgery to determine their post-operative visual acuity and check for complications. All eyes achieved pre-operative corrected vision 16 weeks after LASEK surgery, with no difference being observed between the two groups. However, there was a significant difference in the ophthalmalgia observed 3 days after LASEK surgery, with the flap-removal group experiencing less post-operative pain than those who had the corneal flap preserved. Furthermore, by 3 days post-operation, the observed corneal epithelial healing was significantly different: again the eyes of those who had the corneal flap removed having a faster recovery than those belonging to the corneal preservation group. In conclusion, the patients who had a flap-removal LASEK operation recorded faster recovery and suffered less ophthalmalgia, but there was no significant difference in the overall outcome in terms of post-operative optimally corrected vision or complications such as haze formation.