MicroRNA-20a-5p inhibits the autophagy and cisplatin resistance in ovarian cancer via regulating DNMT3B-mediated DNA methylation of RBP1.

Ovarian cancer (OvCa) is the third most common female malignancy worldwide and poses great threats on women health. Chemotherapy is the most recommended post-surgery treatment for OvCa patients; but, cisplatin resistance is a main cause of chemotherapy failure. In addition, autophagy modulates the sensitivity of tumor cells to chemotherapeutic agents. Hence, it is significant to explore the molecular mechanism concerning the autophagy and cisplatin resistance in OvCa. In this study, quantitative real-time PCR (qRT-PCR) was used to detect miR-20a-5p expression and western blot to measure RBP1 expression. A series of assays were conducted to explore the gain-of-function effects of miR-20a-5p. Luciferase reporter assay was applied to determine the downstream target of miR-20a-5p. The results proved that miR-20a-5p represses malignant phenotypes and autophagy in cisplatin-resistant OvCa cells. In addition, DNMT3B mediates DNA methylation of RBP1 to impair the promoting effects of RBP1 on carcinogenesis and autophagy in OvCa. Through rescue experiments, we certified that miR-20a-5p inhibits the autophagy and cisplatin resistance in OvCa via DNMT3B-mediated DNA methylation of RBP1. Collectively, we demonstrated that miR-20a-5p plays a crucial role in the modulation of autophagy and cisplatin resistance in OvCa, which might offer novel insights into developing effective treatment strategies for OvCa.

LncRNA PART1 Stimulates the Development of Ovarian Cancer by Up-regulating RACGAP1 and RRM2.

Ovarian cancer (OC) is a kind of gynecologic malignancy with a high mortality rate. Long non-coding RNAs (lncRNAs) have been reported to exert regulatory roles in multiple diseases. However, the role of lncRNA prostate androgen-regulated transcript 1 (PART1) has not been investigated in the development of OC. In this study, from RT-qPCR analysis, we discovered that PART1 demonstrated high expression in OC cells. Moreover, data from functional assays manifested that PART1 reduction hindered the proliferative, migratory, and invasive capabilities of OC cells. In vivo uncovered that PART1 knockdown impeded OC tumor growth. Furthermore, from the experimental results of RNA pull down, RIP, and luciferase reporter assays, we discovered that PART1 served as a sponge for microRNA-6884-5p (miR-6884-5p) to modulate the expression of Rac GTPase activating protein 1 (RACGAP1) and ribonucleotide reductase regulatory subunit M2 (RRM2). Finally, rescue assays proved that overexpression of RACGAP1 or RRM2 abrogated the suppressive role of PART1 knockdown on OC cell malignant behaviors. RACGAP1 and RRM2 were also revealed to act as oncogenes in OC cells. In summary, our research verified the PART1/miR-6884-5p/RACGAP1/RRM2 axis in OC cells, which signified that PART1 might act as a novel biomarker in OC.

All­trans retinoic acid promotes macrophage phagocytosis and decreases inflammation via inhibiting CD14/TLR4 in acute lung injury.

Acute lung injury (ALI) is a common clinical emergency and all­trans retinoic acid (ATRA) can alleviate organ injury. Therefore, the present study investigated the role of ATRA in ALI. Lipopolysaccharide (LPS)­induced ALI rats were treated with ATRA and the arterial partial pressure of oxygen (PaO2), lung wet/dry weight (W/D) ratio and protein content in the bronchial alveolar lavage fluid (BALF) were measured to evaluate the effect of ATRA on ALI rats. Alveolar macrophages were isolated from the BALF. The phagocytic function of macrophages was detected using the chicken erythrocyte phagocytosis method and flow cytometry. The viability of macrophages was measured using a Cell Counting Kit­8 assay, and apoptosis was analyzed using a TUNEL assay and flow cytometry. The expression levels of Toll­like receptor 4 (TLR4) and cluster of differentiation (CD)14 on the macrophage membrane were detected by immunofluorescence staining. The protein levels of TLR4, CD14, phosphorylated (p)­65, p65, p­IκBα and IκBα were analyzed using western blotting. The concentrations of IL­6, IL­1ß and macrophage inflammatory protein­2 in the plasma of rats were detected by ELISA. Macrophages were treated with IAXO­102 (TLR4 inhibitor) to verify the involvement of CD14/TLR4 in the effect of ATRA on ALI. ATRA provided protection against LPS­induced ALI, as evidenced by the increased PaO2 and reduced lung W/D ratio and protein content in the BALF. ATRA enhanced macrophage phagocytosis and viability and reduced apoptosis and inflammation in ALI rats. Mechanically, ATRA inhibited CD14 and TLR4 expression and NF­κB pathway activation. ATRA enhanced macrophage phagocytosis and reduced inflammation by inhibiting the CD14/TLR4­NF­κB pathway in LPS­induced ALI. In summary, ATRA inactivated the NF­κB pathway by inhibiting the expression of CD14/TLR4 receptor in the alveolar macrophages of rats, thus enhancing the phagocytic function of macrophages in ALI rats, improving the activity of macrophages, inhibiting apoptosis, reducing the levels of inflammatory factors, and consequently playing a protective role in ALI model rats. This study may offer novel insights for the clinical management of ALI.

An improved correction method for reducing off-focal artifacts in CT imaging.

This paper presents a new method to reduce halo artifacts in Computed Tomography (CT) images, which blur the image edges and descend the image quality. Off-focal radiation is main ill factor leading to these halo artifacts. To reduce the off-focal effects, we adopt a pre-processing method to filter the sampling data directly before reconstruction, instead of post-processing method such as edge enhancing on the reconstructed images. Different from the prior pre-processing method, we also present a new and more practical method to obtain convolution kernel and a simpler formula in this paper. Results show that after calibration by the new practical method, the off-focal radiation effects were reduced efficiently, the edges were enhanced and the image quality was improved without increasing noise.