Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

Background/Aims: Doxorubicin (DOX) is a widely used chemotherapeutic agent for colorectal cancer (CRC). However, the acquirement of DOX resistance limits its clinical application for cancer therapy. Mounting evidence has suggested that aberrantly expressed lncRNAs contribute to drug resistance of various tumors. Our study aimed to explore the role and molecular mechanisms of lncRNA X-inactive specific transcript (XIST) in chemoresistance of CRC to DOX. Methods: The expressions of XIST, miR-124, serum and glucocorticoid-inducible kinase 1 (SGK1) mRNA in DOX-resistant CRC tissues and cells were detected by qRT-PCR or western blot analysis. DOX sensitivity was assessed by detecting IC50 value of DOX, the protein levels of P-glycoprotein (P-gp) and glutathione S-transferase-π (GST-π) and apoptosis. The interactions between XIST, miR-124 and SGK1 were confirmed by luciferase reporter assay, qRT-PCR and western blot. Xenograft tumor assay was used to verify the role of XIST in DOX resistance in CRC in vivo. Results: XIST expression was upregulated and miR-124 expression was downregulated in DOX-resistant CRC tissues and cells. Knockdown of XIST inhibited DOX resistance of CRC cells, as evidenced by the reduced IC50 value of DOX, decreased P-gp and GST-π levels and enhanced apoptosis in XIST-silenced DOX-resistant CRC cells. Additionally, XIST positively regulated SGK1 expression by interacting with miR-124 in DOX-resistant CRC cells. miR-124 suppression strikingly reversed XIST-knockdown-mediated repression on DOX resistance in DOX-resistant CRC cells. Moreover, SGK1-depletion-elicited decrease of DOX resistance was greatly restored by XIST overexpression or miR-124 inhibition in DOX-resistant CRC cells. Furthermore, XIST knockdown enhanced the anti-tumor effect of DOX in CRC in vivo. Conclusion: XIST exerted regulatory function in resistance of DOX possibly through miR-124/SGK1 axis, shedding new light on developing promising therapeutic strategy to overcome chemoresistance in CRC patients

Price discovery and volatility spillovers in the interest rate derivatives market

Abstract The interest rate derivatives market is an important force in promoting the development of the bond market and is an effective tool to manage interest rate risk. The research on price discovery and volatility spillover of the market can help provide valuable reference information for investors. Based on treasury bond futures and interest rate swaps, the paper aims to discuss the price discovery function and spillover structure of the interest rate derivatives market. The paper establishes the information share model and spillover index model for empirical analysis. The results show that: First, the calculation results of the information share model show that the price discovery of treasury bond futures and interest rate swap markets is stronger than that of the spot market. Second, based on structural break analysis, treasury bond futures and interest rate swaps do not have breakpoints, while the treasury bond spot has three breakpoints. The paper divides the entire sample into four stages based on structural breakpoints and finds that the price discovery ability of the interest rate derivative market dynamically changed. Third, as a net spillover in the market, treasury bond futures have developed relatively stable. Both treasury bond futures and interest rate swaps have spillover effects on the spot market, indicating that China’s interest rate derivatives market can impact the treasury bond spot market

Assessment of Renal Pathological Changes in Lupus Nephritis Using Diffusion Weighted Imaging: A Multiple Correspondence Analysis

Background/Aims: Renal pathological changes affect the motion of water molecules, which can be detected using diffusion-weighted imaging (DWI). The current study was performed to explore the correlation between renal tissue pathological injuries and DWI iconographical parameters in lupus nephritis (LN). Methods: Twenty adult patients with LN and 11 healthy volunteers were recruited. Patients with LN received renal biopsies and renal DWI-MRI inspections. The renal biopsy tissues were characterized based on the ISN/RPS 2003 classification. The volunteers, who were of comparable gender and age, only underwent renal DWI-MRI inspection. Four DWI parameters, namely, apparent diffusion coefficient (ADC), pure diffusion coefficient (Dt), pseudo-diffusion coefficient (Dp), and perfusion fraction (fp), were calculated using monoexponential and biexponential functions, respectively. Data from different renal areas and pathological pattern groups were compared. Multiple correspondence analysis (MCA) was performed to explore the correlation between each DWI index and multiple pathological features. Results: ADC, Dt, and fp values were lower in the LN group compared to the controls (P < 0.001) regardless of the renal area in the cortex and medulla. Dp values were higher in the LN group (P = 0.004). A difference in mean DWI parameters was found between three LN subgroups and the healthy volunteers, with the exception of the Dp index in the renal cortex. MCA showed that serious proliferative pathological injuries and lower ADC and Dt values were located in the same quadrant. The MCA plots of Dp and fp provided similar results. Higher Dp and fp values were located in the MCA plot quadrant with more serious proliferative pathological changes. Conclusion: DWI is a noninvasive technique that may be used to detect renal pathophysiological changes. Renal cell proliferation and intestinal fibrosis may impact the movement of water in certain microenvironments. Enhanced perfusion may be a compensatory mechanism that is associated with renal pathological injuries

Additional file 2: of Blood oxygen level dependent magnetic resonance imaging for detecting pathological patterns in lupus nephritis patients: a preliminary study using a decision tree model

Decision tree model for predicting class III and class IV of lupus nephritis with CHIAD algorithm. (PDF 11.4 mb