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Objective To explore the effect of long noncoding RNA cancer susceptibility 2 (lncRNA CASC2) on the sensitivity of glioma cells to temazolamide (TMZ) and investigate the underling mechanism. Methods Forty glioma tissue samples derived from the 40 patients undergoing surgical treatment in our department from July 2018 to March 2020 were enrolled in this study. The expression of lncRNA CASC2 in the glioma tissues was detected with RT-PCR, and the results were analyzed with pathological grades and compared between the patients with isocitrate dehydrogenase (IDH) 1/2 mutant (n=17) and IDH 1/2 wild type (n=9). Glioma cells U251 were cultured and transfected with plasmid pc-CASC2 to overexpress lncRNA CASC2 and/or interfering RNA of multi-drug resistance protein ABCG2. CCK-8 assay and flow cytometry were used to detect the cell viability and apoptotic rate in above cell groups after 30 μg/mL TMZ treatment. After mouse intracranial glioma model was established, high performance liquid chromatography was adopted to determine the concentration of TMZ. The correlation between lncRNA CASC2 and ABCG2 was detected by immunofluorescence staining and RNA immunoprecipitation. Results LncRNA CASC2 level was decreased in the glioma tissues with IDH 1/2 wild type, and had a negative correlation with pathological grade of glioma. LncRNA CASC2 overexpression resulted in significantly lower IC50 to TMZ (36.7±4.2 μg/mL) than the U251 cells after pc-Null transfection (t=4.41, P < 0.05). Under 30 μg/mL TMZ stimulation, the cell viability was reduced and the proportion of apoptotic cells was increased after lncRNA-CASC2 overexpression. In the mouse intracranial glioma model, the concentration of intracellular TMZ active product was increased after lncRNA-CASC2 overexpression. LncRNA CASC2 and ABCG2 were evenly distributed in the cytoplasm, and RNA immunoprecipitation showed that the content of lncRNA CASC2 in ABCG2 antibody group was higher than that in IgG control group. In addition, down-regulation of intracellular ABCG2 by siRNA decreased the TMZ sensitivity of U251 cells that could enhanced by lncRNA CASC2. Conclusion LncRNA CASC2 improves the sensitivity of glioma U251 cells to TMZ. However, ABCG2 inhibition by siRNA attenuates the above effects of lncRNA CASC2.

Objective To investigate whether long non-coding (lnc) RNA GASL1 can promote the proliferation of vascular smooth muscle cells (VSMCs) by activating the Wnt/β-catenin signaling pathway. Methods The mRNAs co-expression network related to lncRNA GASL1 was constructed and analyzed with Pathway analysis to predict the signaling pathway of the highest correlation with lncRNA GasL1. After LncRNA GASL1 and lncRNA negative control (lncRNA NC) were transfected into VSMCs respectively, cell counting kit-8 (CCK-8) assay was performed to detect VSMCs viability. Immunofluorescence assay was performed to determine the expression level of proliferation-related protein Bcl-2, and Western blotting to detect the levels of the proteins of Wnt/β-catenin signaling pathway. Finally, Wnt/β-catenin pathway inhibitor ICG001 was added into VSMCs along with lncRNA GASL1 for co-culturing (lncRNA GASL1+ ICG001 group), and the alterations of VSMCs viability and bcl-2 protein level were detected and compared with those in the lncRNA GASL1+ control group. Results There were 374 mRNAs associated with lncRNA GASL1, of which the Wnt/β-catenin pathway had the highest correlation. CCK-8 assay showed that the VSMCs viability was higher in the lncRNA GASL1 group than in the lncRNA NC group (P < 0.05). The results of immunofluorescence assay and Western blotting revealed that both the Bcl-2 protein level and the levels of Wnt1 and β-catenin were increased in lncRNA GASL1 group (P < 0.05) when compared to the lncRNA-NC group. After co-culturing with lncRNA GASL1 and ICG001, the VSMCs viability was significantly decreased (P < 0.05), and the Bcl-2 protein level was decreased when compared with the the lncRNA GASL1+control group (P < 0.05). Conclusion LncRNA GASL1 promotes the proliferation of VSMCs through the Wnt/β-catenin signaling pathway. Blocking the signaling pathway can reduce the promotive effect of lncRNA GASL1 on VSMCs.

Column experiments were conducted to examine the clogging effects of colloids under controlled conditions of solution ionic strength (IS) and porous media roughness. The results showed that colloids in recharge water play an important role in the clogging process of saturated porous media, such that even a small amount of colloid may cause a large reduction in the permeability of the porous medium. Clogging at the pore throat was inferred to be the main reason for the severe permeability reduction of porous media. The characteristics of colloid clogging were clearly influenced by both IS and medium roughness. Recharge water with a higher IS facilitated greater attachment of colloids to the surface of the saturated porous medium, which lead to superficial clogging, while collectors with a rough surface resulted in greater clogging than collectors with a smooth surface.

Background: The volume doubling time (VDT) of breast cancer was most frequently calculated using the two‐dimensional (2D) diameter, which is not reliable for irregular tumors. It was rarely investigated using three‐dimensional (3D) imaging with tumor volume on serial magnetic resonance imaging (MRI). Purpose: To investigate the VDT of breast cancer using 3D tumor volume assessment on serial breast MRIs. Study Type: Retrospective. Subjects: Sixty women (age at diagnosis: 57 ± 10 years) with breast cancer, assessed by two or more breast MRI examinations. The median interval time was 791 days (range: 70–3654 days). Field Strength/Sequence: 3‐T, fast spin‐echo T2‐weighted imaging (T2WI), single‐shot echo‐planar diffusion‐weighted imaging (DWI), and gradient echo dynamic contrast‐enhanced imaging. Assessment: Three radiologists independently reviewed the morphological, DWI, and T2WI features of lesions. The whole tumor was segmented to measure the volume on contrast‐enhanced images. The exponential growth model was fitted in the 11 patients with at least three MRI examinations. The VDT of breast cancer was calculated using the modified Schwartz equation. Statistical Tests: Mann–Whitney U test, Kruskal–Wallis test, Chi‐squared test, intraclass correlation coefficients, and Fleiss kappa coefficients. A P‐value <0.05 was considered statistically significant. The exponential growth model was evaluated using the adjusted R2 and root mean square error (RMSE). Results: The median tumor diameter was 9.7 mm and 15.2 mm on the initial and final MRI, respectively. The median adjusted R2 and RMSE of the 11 exponential models were 0.97 and 15.8, respectively. The median VDT was 540 days (range: 68–2424 days). For invasive ductal carcinoma (N = 33), the median VDT of the non‐luminal type was shorter than that of the luminal type (178 days vs. 478 days). On initial MRI, breast cancer manifesting as a focus or mass lesion showed a shorter VDT than that of a non‐mass enhancement (NME) lesion (median VDT: 426 days vs. 665 days). Data Conclusion: A shorter VDT was observed in breast cancer manifesting as focus or mass as compared to an NME lesion. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Tertiary lymphoid structure (TLS) represents lymphocyte clusters in non-lymphoid organs. The formation and maintenance of TLS are dependent on follicular helper T (TFH) cells. However, the role of TFH cells during renal TLS formation and the renal fibrotic process has not been comprehensively elucidated in chronic kidney disease. Here, we detected the circulating TFH cells from 57 IgAN patients and found that the frequency of TFH cells was increased in IgA nephropathy patients with renal TLS and also increased in renal tissues from the ischemic-reperfusion-injury (IRI)-induced TLS model. The inducible T-cell co-stimulator (ICOS) is one of the surface marker molecules of TFH. Remarkably, the application of an ICOS-neutralizing antibody effectively prevented the upregulation of TFH cells and expression of its canonical functional mediator IL-21, and also reduced renal TLS formation and renal fibrosis in IRI mice in vivo. In the study of this mechanism, we found that recombinant IL-21 could directly promote renal fibrosis and the expression of p65. Furthermore, BAY 11-7085, a p65 selective inhibitor, could effectively alleviate the profibrotic effect induced by IL-21 stimulation. Our results together suggested that TFH cells contribute to TLS formation and renal fibrosis by IL-21. Targeting the ICOS-signaling pathway network could reduce TFH cell infiltration and alleviate renal fibrosis. [ABSTRACT FROM AUTHOR]