Extracellular vesicles released by hypoxia-induced tumor-associated fibroblasts impart chemoresistance to breast cancer cells via long noncoding RNA H19 delivery.

Recently, extracellular vesicles (EVs) have been emphasized in regulating the hypoxic tumor microenvironment of breast cancer (BC), where tumor-associated fibroblasts (TAFs) play a significant role. In this study, we describe possible molecular mechanisms behind the pro-tumoral effects of EVs, secreted by hypoxia (HP)-induced TAFs, on BC cell growth, metastasis, and chemoresistance. These mechanisms are based on long noncoding RNA H19 (H19) identified by microarray analysis. We employed an in silico approach to identify differentially expressed lncRNAs that were associated with BC. Subsequently, we explored possible downstream regulatory mechanisms. We isolated EVs from TAFs that were exposed to HP, and these EVs were denoted as HP-TAF-EVs henceforth. MTT, transwell, flow cytometry, and TUNEL assays were performed to assess the malignant phenotypes of BC cells. A paclitaxel (TAX)-resistant BC cell line was constructed, and xenograft tumor and lung metastasis models were established in nude mice for in vivo verification. Our observation revealed that lncRNA H19 was significantly overexpressed, whereas miR-497 was notably downregulated in BC. HP induced activation of TAFs and stimulated the secretion of EVs. Coculture of HP-TAF-EVs and BC cells led to an increase in TAX resistance of the latter. HP-TAF-EVs upregulated methylation of miR-497 by delivering lncRNA H19, which recruited DNMT1, thus lowering the expression of miR-497. In addition, lncRNA H19-containing HP-TAF-EVs hindered miR-497 expression, enhancing tumorigenesis and TAX resistance of BC cells in vivo. Our study presents evidence for the contribution of lncRNA H19-containing HP-TAF-EVs in the reduction of miR-497 expression through the recruitment of DNMT1, which in turn promotes the growth, metastasis, and chemoresistance of BC cells.

Laparoscopic Surgery Combined with GnRH Agonist in Endometriosis.

OBJECTIVE: To determine the efficacy of laparoscopic surgery combined with GnRH agonist (GnRH-a) in treating infertile patients with endometriosis (EMs), and analyze its effect on the levels of serum hormones and inflammatory factors of the patients. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: The Department of Urology, Zhongda Hospital, Southeast University, Jiang Su, China, from January 2015 to March 2016. METHODOLOGY: One hundred and thirty infertile patients with EMs were randomly divided into a control group and an observation group with 65 cases in each group. Patients in the control group were treated by laparoscopic surgery, while patients in the observation group were added by the subcutaneous injection of GnRH-a, based on the treatment of the control group. Therapeutic effects, recurrence rates, and pregnancy rates between two groups were compared. Moreover, the levels of serum hormones estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), inflammatory factors interleukin 17 (IL-17), interleukin 6 (IL-6), and tumor necrosis factor- (TNF-α) between two groups after treatment were compared. RESULTS: The total effective rate and pregnancy rate in the observation group were higher than those of the control group (p=0.009 and 0.002, respectively), and the recurrence rate was lower than that of the control group (p=0.008). After treatment, levels of serum E2, LH, FSH in the observation group were lower than those of the control group (all p<0.001). Levels of serum IL-17, IL-6 and TNF-α were lower than those of the control group (all p<0.001). There was no statistically significant difference in adverse reactions between the two groups (p=0.730). CONCLUSION: Laparoscopic surgery combined with GnRH-a is a more effective treatment modality in endometriosis. It can reduce the serum levels of inflammatory factors in patients, improve their hormone level and pregnancy rate, and reduce the recurrence rate.

Zirconium-Based Porphyrinic Metal-Organic Framework (PCN-222): Enhanced Photoelectrochemical Response and Its Application for Label-Free Phosphoprotein Detection.

A simple and rapid photoelectrochemical (PEC) sensor was developed for the label-free detection of a phosphoprotein (α-casein) based on a zirconium based porphyrinic metal-organic framework (MOF), PCN-222, which exhibited an enhanced photocurrent response toward dopamine under the O2-saturated aqueous media. In this work, in terms of PEC measurements and cyclic voltammetry, the PEC behaviors of PCN-222 in aqueous media were thoroughly investigated for the first time. Additionally, in the virtue of the steric hindrance effect from the coordination of the phosphate groups and inorganic Zr-O clusters as binding sites in PCN-222, this biosensor showed high sensitivity for detecting α-casein and the limit of detection (LOD) was estimated to be 0.13 µg mL-1. Moreover, the proposed method provides a promising platform for clinic diagnostic and therapeutics.