Circular RNA ERBB2 Contributes to Proliferation and Migration of Airway Smooth Muscle Cells via miR-98-5p/IGF1R Signaling in Asthma.

BACKGROUND: Asthma belongs to chronic inflammatory respiratory diseases characterized by airway inflammation and remodeling. Circular RNAs (circRNAs) are promising therapeutic targets for various diseases, including asthma. In this work, we aim to investigate the role of circular RNA Erb-B2 receptor tyrosine kinase 2 (circERBB2) during progression of asthma. METHODS: Human airway smooth muscle cells (ASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) to mimic cell remodeling. The expression of circERBB2, microRNA-98-5p (miR-98-5p), and insulin-like growth factor 1 receptor (IGF1R) was measured by qRT-PCR. Cell proliferation, migration and apoptosis were determined by cell counting-8 (CCK-8), transwell, and flow cytometry. Protein levels of PCNA, MMP-9, IGF1R were evaluated using Western blotting. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Luciferase reporter gene experiment was adopted to evaluate the targeting relationship between miR-98-5p with circERBB2 and IGF1R. Interaction between RNAs was determined by RNA pulldown and RIP assay. RESULTS: The depletion of circERBB2 attenuated the proliferation, migration, and levels of inflammatory factors induced by PDGF-BB and cell apoptosis. CircERBB2 was identified to directly interact with miR-98-5p, and overexpression of miR-98-5p abolished the function of circERBB2 on PDGF-BB-stimulated ASMCs. IGF1R was identified as a target of miR-98-5p, and knockdown of IGF1R relieved the PDGF-BB-induced ASMCs proliferation and migration. CONCLUSION: Our work disclosed that knockdown of circERBB2 suppressed PDGF-BB-caused proliferation, migration and inflammatory response of ASMCs, through regulating miR-98-5p/IGF1R signaling, presented circERBB2 as a promising therapeutic target for asthma.

Cyanidin-3-O-glucoside promotes progesterone secretion by improving cells viability and mitochondrial function in cadmium-sulfate-damaged R2C cells.

Cadmium (Cd) is a poisonous metal that is toxic for male reproduction. Cyanidin-3-O-glucoside (C3G) as typical anthocyanin benefits many organs. In this study, we investigated the protective effects and associated underlying mechanisms of C3G against the toxicity of Cd on male reproduction in rat Leydig cell line R2C cells. Cells were pre-protected with C3G (5-160 µmol/L) for 2 h and then treated with cadmium sulfate (CdSO4) (10-160 µmol/L) for 24 h. The results showed that cytotoxicity, mitochondrial damage, superoxide dismutase 2 (SOD2), and overproduction of reactive oxygen species (ROS) in CdSO4-treated R2C cells were significantly reduced with C3G pre-treatment. Moreover, C3G pre-treatment led to upregulated expression of steroidogenic acute regulatory (StAR) protein and progesterone production. Our study suggests that C3G may be a potential therapeutic agent against Cd-induced reproductive toxicity.

Association of matrix metalloproteinase-10 polymorphisms with susceptibility to pelvic organ prolapse.

AIM: The aim of this study was to explore the correlation between genetic mutations in matrix metalloproteinase-10 (MMP-10) and susceptibility to pelvic organ prolapse (POP). MATERIAL AND METHODS: From September 2011 to December 2013, 263 subjects were recruited, including 91 patients with POP (case group) and 172 non-POP patients (control group). Total MMP-10 concentrations in serum were measured by enzyme-linked immunosorbent assay. The genotyping of MMP-10 was achieved by quantitative real-time polymerase chain reaction. All data were analyzed with SPSS 18.0. RESULTS: We found that parity, menopause, history of total hysterectomy, and family history of POP were all significantly higher in the POP group than in the control group (P = 0.017, P = 0.046, P = 0.0029 and P < 0.001, respectively). Serum MMP-10 levels were obviously higher in the POP group than in the control group (P < 0.05). In addition, there was a statistically significant difference between the two groups in the distribution frequency of the MMP-10 (rs17435959G/C) genotype (P < 0.05). However, the distribution frequency of the MMP-10 (rs17293607C/T) genotype between the two groups showed no significant differences (P > 0.05). Furthermore, the patients with parity > 2 and postmenopausal women had elevated serum MMP-10 levels, and the patients with parity > 2 and postmenopausal women who carried the G/C + C/C genotype in the MMP-10 gene had an increased risk of POP. CONCLUSION: We support the view that the rs17435959 polymorphism of the MMP-10 gene may be associated with an increased risk of POP.

[Multicenter randomized, double-blind, placebo-controlled trial of prostaglandin E1 cream for female sexual arousal disorder].

OBJECTIVE: To investigate the efficacy and safety of alprostadil cream in management of female sexual arouse disorder (FSAD), and its appropriate dose for clinical prescription. METHODS: The volunteers were assigned randomly to four groups which received alprostadil cream in different dosage (500 µg, 700 µg and 900 µg) or placebo cream, respectively. The cream was applied to the clitoris and G-spot before coitus. The efficacy was assessed by comparing the satisfactory rate of sexual arousal, the score of female sexual function index (FSFI) and female sex disorder scale (FSDS) and the general appraised question (GAQ) before and after the treatment. The safety was evaluated by the adverse effects that appeared including symptoms, physical and biochemical examination. RESULTS: Totally, 400 women enrolled in this study with 374 assigned to the group for efficacy evaluation and 387 cases to the group for safety analysis. No significant difference was found among the four groups in the demographic characters and sexual baseline. The increase of satisfactory percentage of sexual arousal in the four groups (placebo, 500 µg, 700 µg and 900 µg) was 22.63%, 36.67%, 34.01%, and 44.29%, respectively (P<0.05), and the increase was statistically higher in the 900 µg group than in the placebo group (P<0.0167). The elevated FSFI score above the baseline in the treatment groups (900 µg 22.89, 700 µg 21.69, and 500 µg 20.71) were higher than that in the placebo group (14.68, P<0.05), while the reduced FSDS score below the baseline (900 µg 25.97, 700 µg 21.98, and 500 µg 20.27) were higher than that of the placebo (17.60, P<0.05). No significant difference was found in the four groups in GAQ (P=0.054). The main common adverse effect was topical stimulation. No adverse effect was reported in physical and biochemical examination, electrocardiogram (ECG) or Thinprep cytologic test (TCT). CONCLUSION: Alprostadil cream can treat female sexual arousal disorder effectively with the maximum effect at the dose of 900 µg and without significant adverse effect except for mild topical stimulation.

[A multicenter prospective randomized open comparative study on the treatment of ovulatory menorrhagia with tranexamic acid and norethisterone in China].

OBJECTIVE: To compare the efficacy and safety of tranexamic acid (TA) and norethisterone (NET) for the treatment of patients with ovulatory menorrhagia in China. METHODS: One hundred and thirty one patients with proven ovulatory menorrhagia from gynecologic clinics of 5 teaching hospitals located in 4 different cities in China were enrolled during Jul 2004 to Dec 2006. Among them 128 completed the study. Patients were randomly divided into two therapeutic regimen groups: TA 1 g thrice daily during menstrual cycle days (D) 1-5, 69 cases; or NET 5 mg twice daily on D19-26, 59 cases. The drugs were administered for 2 consecutive cycles, then withdrawn and patients were followed-up for 1 more cycle. Data on menstrual blood loss [estimated by pictorial blood assessment chart (PBAC)], length of menstrual periods, quality of life (QOL) evaluated by a 6 item health-related questionnaire were collected before, during each cycle and were compared. RESULTS: Both treatments led to significant decreases of mean PBAC scores and shorter duration of menstrual periods, and improved the QOL ranking during the two treatment cycles. The mean percentages of PBAC decrements in the TA first and second cycles were significantly greater than those in the NET corresponding cycles(35% vs 17% , P = 0.004; 44% vs 34%, P = 0.04 respectively). The success rate of TA second cycle was higher than that of the NET second cycle (41% vs 24%, P = 0.04). Improvement of QOL ranking in the TA first cycle was also significantly better than those in the NET first cycle (P = 0.03). The percentage of patients with at least 1 adverse event in TA group (19%) was significantly lower than that in NET group (35%, P = 0.04). Patients' willingness to continue the treatment in the TA second and follow-up cycles (94%, 79% respectively) were significantly higher than those in the corresponding cycles of NET groups (79%, 59% respectively; P = 0.01, P = 0.02). CONCLUSION: The regimen of TA 3 g daily during menstrual days 1-5 is a more effective and tolerable treatment than luteal phase norethisterone for patients with ovulatory menorrhagia.