Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).@*METHODS@#The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.@*RESULTS@#The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.@*CONCLUSION@#Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

The Effect of Vaginal Oestriol Cream on Subjective and Objective Symptoms of Stress Urinary Incontinence and Vaginal Atrophy: An International Multi-Centre Pilot Study.

AIM: Subjectively and objectively assess stress urinary incontinence (SUI) symptoms before and after topical oestrogen therapy. METHODS: A prospective study was performed in 3 centres in South-Africa, Australia and the Netherlands. Postmenopausal women with SUI were treated with topical oestriol cream for 6 weeks. The primary subjective outcome was the Patient's Global Impression of Improvement (PGI-I) scale. The primary objective outcome was vaginal pH. Secondary subjective outcomes were: the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form, the Incontinence Impact Questionnaire, the Urogenital Distress Inventory (UDI-6) and the most bothersome symptom approach. Secondary objective outcome was the erect cough pad test. Compliance was scored. RESULTS: A total of 68 women were enrolled. Half of the participants reported improvement on the PGI-I scale after treatment. Vaginal pH was significantly lower after treatment (median 5.3 (interquartile range (IQR) 4.5-6.0) vs. 5.0 (4.4-5.4), p = 0.002). Improvement on the UDI stress domain was observed (p = 0.01). No statistically significant differences were found in the other subjective outcomes. Baseline and repeat cough pad tests demonstrated a wide variation with no significant difference. Compliance was high (median 100 (IQR 83-100%)). CONCLUSION: Topical oestriol cream during 6 weeks improved quality of life and vaginal pH but no other objective measures of incontinence.

Pregnancy outcomes before and after institution of a specialised twins clinic: a retrospective cohort study.

BACKGROUND: Although specialised clinics for multiple pregnancies are recommended by several Obstetrics and Gynaecology governing bodies, studies examining outcome before and after introduction of such clinics remain few, were performed predominantly in North America in the 1990s, and either amongst dichorionic twin pregnancies only or where chorionicity was not specified. Our objective, in the modern setting with twins of known chorionicity, was to compare maternal and neonatal outcomes of twin pregnancies before and after commencement of a consultant-led, multidisciplinary twins clinic (TC). METHODS: Retrospective cohort study of 513 women, with birth of twins at ≥20 weeks' gestation, January 2007 to November 2011, at a metropolitan tertiary maternity hospital, Sydney, Australia. Demographic, pregnancy, and outcome data were obtained from hospital databases. Women receiving TC care (2009-2011) were compared to those receiving general antenatal clinic (ANC) care (2007-2010) and private care (2009-2011). Other models of care were excluded. Main outcome measures were total maternal inpatient stay, mode of birth, gestational age at birth, and neonatal nursery admission. RESULTS: 286 women were included in the main analyses: 84 attended ANC, 101 TC, and 101 a private obstetrician. TC women had similar demographics to ANC women and were slightly younger than private patients. TC women had lower Caesarean section rates (55% vs. 70% ANC and 76% private, p = 0.008) and fewer late preterm (34 + 0-36 + 6 weeks) births, (26%TC vs. 44% ANC and 41% private, p < 0.001). Median maternal inpatient stay was shorter in TC than ANC (7 vs. 8 days, p = 0.009) and similar to private (7 days). Nursery admission rates were higher in private patients (67% vs. 49% ANC and 47% TC, p = 0.001) and average birthweight lower (2283 g vs. 2501 g ANC and 2496 g TC, p < 0.001). CONCLUSIONS: Within a single centre, maternal and neonatal twin pregnancy outcomes varied significantly by model of care. Introducing a specialised twins clinic in our setting decreased Caesarean section rates, late preterm birth, and inpatient stay compared to ANC.

Recent studies of genetic dysfunction in pelvic organ prolapse: the role of collagen defects.

Gynaecologists are becoming increasingly aware that women with a family history of prolapse are at an increased risk of prolapse refractory to treatment. In the past five years, several genetic mutations have been shown to correlate with increased prolapse susceptibility. These mutations can result in disordered collagen metabolism, which weaken the fascial support of the pelvic organs. This review examines the contemporary evidence regarding the role of collagen in prolapse.