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Pallesen Gaarde posted an update 6 hours, 34 minutes ago
At month 18, grade ≥ 2 GU and GI toxicity decreased below 5% and 2% for both arms. No changes in EORTC QLQ-PR25 scores for GU, GI, and sexual domains were observed in both arms between baseline and month 18. Four biochemical failures were observed, 2 in each arm, rejecting the null hypothesis of an unfavorable response rate ≤ 85% in favor of an acceptable ≥ 95% rate. CONCLUSIONS At 18 months, urethra-sparing SBRT showed a low toxicity profile, with minimal impact on QoL and favorable biochemical control rates, regardless of overall treatment time (EOD vs QW). © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.BACKGROUND Cockayne syndrome (CS) is a rare autosomal recessive disorder which displays multiorgan dysfunction, especially within the nervous system including psychomotor retardation, cerebral atrophy, microcephaly, cognitive dysfunction, mental retardation, and seizures. Many genetic variations reported were related to this syndrome, but splicing mutations with cardiac anomalies have not been found in previous studies. METHODS Herein, we described a pair of brothers and sisters who present essential manifestations of CS including premature feature, developmental delay, growth failure, microcephaly, and characteristic facial features, such as sunken eyes and a beaked nose. Interestingly, the brother also presented with atypical features which included cardiac anomalies such as left atrioventricular enlargement and cardiac dysfunction such as dilated cardiomyopathy. In addition, whole exome sequencing and RNA sequencing were employed to analyze their genetic landscape. Selleckchem CHIR-99021 RESULTS WES analysis showed that these two cases carried double unreported heterozygous spliced mutations in the excision repair cross-complementing group 8 (ERCC8, also known as CSA, NM_000082) gene, which were c.78-2 (IVS1) A>T and c.1042-1 (IVS10) G>A, respectively. Moreover, transcript sequencing analysis validated these mutation sites. In this study, Gene Ontology enrichment and KEGG pathway analyses from RNA sequencing demonstrated similarities but some differences when compared with previous studies. CONCLUSION For patients with Cockayne syndrome, cardiac changes need to be monitored carefully, especially for cases with splicing mutations of the ERCC8 gene. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.Thioredoxin (Trx) is a hydrogen acceptor of ribonucleotide reductase, and a regulator of some enzymes and receptors. It has been previously shown that significantly elevated levels of Trx expression are associated with the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but it is not clear how Trx regulates the effects of hydrogen peroxide on myogenic differentiation of BMSCs. Here, we report that rat BMSCs treated with a high dose (150 µmol/L) of H2 O2 exhibited a significant reduction in viability, cell cycling, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels, and an increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, which was accompanied by reductions in AKT activation and FoxO1, MyoD1 and myogenin expression during myogenic differentiation. Furthermore, treatment with recombinant human (rh)Trx significantly mitigated the effects of H2 O2 on the myogenic differentiation of BMSCs, and this was abrogated by co-treatment with wortmannin (a specific PI3K inhibitor). In summary, our results suggest that treatment with rhTrx mitigates H2 O2 -induced oxidative stress and may promote myogenic differentiation of rat BMSCs by enhancing PI3K/AKT/FoxO1 signaling. This article is protected by copyright. All rights reserved.On-site identification and quantification of chemicals is critical for promoting food safety, human health, homeland security risk assessment, and disease diagnosis. Surface-enhanced Raman spectroscopy (SERS) has been widely considered as a promising method for on-site analysis due to the advantages of nondestructive, abundant molecular information, and outstanding sensitivity. However, SERS for on-site application has been restricted not only by the cost, performance, and portability of portable Raman instruments, but also by the sampling ability and signal enhancing performance of the SERS substrates. In recent years, the performance of SERS for on-site analysis has been improved through portable Raman instruments, SERS substrates, and other combined technologies. In this review, popular commercial portable Raman spectrometers and the related technologies for on-site analysis are compared. In addition, different types of SERS substrates for on-site application are summarized. SERS combined with other technologies, such as electrochemical and microfluidics are also presented. The future perspective of SERS for on-site analysis is also discussed. © 2020 John Wiley & Sons, Ltd.Circular RNA YAP1 (circYAP1) was reported to participate in progression of gastric cancer. However, the role of circYAP1 in acute kidney injury (AKI) remains obscure. We attempted to examine the effects of circYAP1 on ischaemia/reperfusion-stimulated renal injury. AKI model was established by treating HK-2 cells in ischaemia/reperfusion (I/R) environment. CircYAP1 expression in blood of AKI patients and I/R-treated HK-2 cells was evaluated via RT-qPCR. CCK-8, flow cytometry, ELISA and ROS assay were executed to test the impact of circYAP1 on cell viability, apoptosis, inflammatory cytokines and ROS generation. Bioinformatic analysis was executed to explore miRNA targets. The relativity between circYAP1 and miR-21-5p was verified by RT-qPCR and luciferase assay. The functions of miR-21-5p in I/R-triggered injury were reassessed. PI3K/AKT/mTOR pathway was detected by Western blot. Down-regulated circYAP1 was observed in AKI blood samples and I/R-treated HK-2 cells. CircYAP1 overexpression expedited cell growth and weakened secretion of inflammatory factors and ROS generation in I/R-disposed cells. Besides, we found circYAP1 could sponge to miR-21-5p. Interestingly, miR-21-5p overexpression overturned the repressive effects of circYAP1 on cell injury. Moreover, PI3K/AKT/mTOR pathway was activated by circYAP1 via inhibiting miR-21-5p. We demonstrated that circYAP1 activated PI3K/AKT/mTOR pathway and secured HK-2 cells from I/R injury via sponging miR-21-5p. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.