Several studies have suggested that long intergenic noncoding RNAs are involved in the progression of diabetic nephropathy (DN). However, the exact role and regulatory mechanism of long noncoding RNA (lncRNA) NR_038323 in diabetic nephropathy (DN) remain largely unclear. In the present study, we found that lncRNA NR_038323 overexpression ameliorated the high glucose (HG)-induced expression levels of collagen I, collagen IV, and fibronectin, whereas lncRNA NR_038323 knockdown exerted the opposite effects. Moreover, the results of bioinformatic prediction, luciferase assay, and fluorescence in situ hybridization (FISH) demonstrated that lncRNA NR_038323 directly interacted with miR-324-3p. Additionally, miR-324-3p mimic aggravated the HG-induced expression levels of collagen I, collagen IV, and fibronectin by dual-specificity protein phosphatase-1 (DUSP1) expression to activate p38 mitogenactivated protein kinase (MAPK) and ERK1/2 pathways. In contrast, overexpression of DUSP1 attenuated the HG-induced expression levels of collagen I, collagen IV, and fibronectin via inactivation of p38 MAPK and ERK1/2 pathways. In addition, lncRNA NR_038323 knockdown increased the expression levels of collagen I, collagen IV, and fibronectin by upregulating DUSP1 expression during HG treatment, which were markedly reversed by miR-324-3p inhibitor. Furthermore, these molecular changes were verified in the human kidney samples of DN patients. Finally, overexpression of lncRNA NR_038323 ameliorated the interstitial fibrosis in STZ-induced diabetic nephrology (DN) rat via miR-324-3p/DUSP1/p38MAPK and ERK1/2 axis. In conclusion, our data indicate that overexpression of lncRNA NR_038323 may suppress HG-induced renal fibrosis via the miR-324-3p/DUSP1/p38MAPK and ERK1/2 axis, which provides new insights into the pathogenesis of DN.

Bladder cancer remains a very challenging disease to treat with the high rates of recurrence and progression associated with current therapies. Although the association between bladder cancer pathology and circRNAs remains undetermined, circRNAs signatures may be useful as prognostic and predictive factors and clinical tools for assessing disease state, treatment response and outcome. This study investigates if these circRNAs can be used as biomarkers for bladder cancer diagnosis and predicting treatment response. Herein, qPCR measured the expression of hsa_circRNA_100783, hsa_circ_0000285 and hsa_circRNA_100782 in bladder cancer tissues. It was established that sa_circ_0000285, but not hsa_circRNA_100782 and hsa_circRNA_10078, are significantly reduced in bladder cancer tissues and serum compared to adjacent tissues and healthy controls. Moreover, hsa_circ_0000285 expression was lower in cisplatin-resistant bladder cancer patients than in those who were cisplatin-sensitive. Here, hsa_circ_0000285 was associated with tumor size (p<0.001), differentiation (p<0.001), lymph node metastasis (p=0.038), distant metastasis (p=0.004) and TNM stage (p=0.013). Further analysis showed that hsa_circ_0000285 would be an independent prognostic factor for bladder cancer patient outcome. In conclusion, our study indicates hsa_circ_0000285 may be a novel biomarker for bladder cancer because of its involvement in bladder cancer chemo-sensitivity.

Harvest control rules (HCRs) for sustainable fishery management have been developed for data-limited fish species for which stock assessments cannot be conducted. However, HCRs have largely not considered mixed-species catches, as when fishing-effort data are widely pooled for numerous minor species in a multispecies fishery. Presently, a feedback HCR has been successfully applied in Japanese fisheries management. By combining management strategy evaluation with a simulation to generate mixed-species data from a multispecies fishery that assume constant catchability (q) among species, we evaluated the performance of this feedback HCR and then compared its performance using species-specific data. In most cases, the biomass was controlled over that needed for maximum sustainable yield (MSY), and the fishing effort was under the fishing mortality consistent with achieving MSY (FMSY). However, for slow-growing species, the biomass might become lower than what is required to remain capable of producing MSY, even though fishing effort was controlled under FMSY. The results show that the feedback HCR is appropriate for multispecies fisheries management where only mixed-species data are available but with special monitoring for slow-growing minor species.

Recent studies have shown that autophagy exhibits a renoprotective role in various models of acute kidney injury (AKI). However, its role in vancomycin (Van)‐induced AKI remains largely unclarified. This study was the first to indicate that autophagy was rapidly activated in both human kidney‐2 cells and renal tissues, and mammalian target of rapamycin (mTOR) was inactivated via the suppression of ERK1/2 and mTOR during Van treatment. Interestingly, for both in vitro and in vivo experiments, the suppression of autophagy via chloroquine and PT‐Atg7‐KO significantly ameliorated Van‐induced kidney injury and renal tubular cell apoptosis. Global gene expression analysis indicated that the expression levels of 6159 genes were induced by Van treatment in the kidney cortical tissues of PT‐Atg7 wild‐type mice, and 18 of them were notably suppressed in PT‐Atg7‐KO mice. These 18 genes were further classified as programmed cell death, protein binding, signal transduction, E3 ubiquitin ligase, nucleoside diphosphate kinase activity, and E1‐like activating enzyme. Unexpectedly, following Van treatment, PKC‐δ expression was found to be highest among the 4 genes related to cell death, which was remarkably suppressed in vitro and in PT‐Atg7‐KO mice. In addition, Atg7 could induce renal cell apoptosis during Van treatment via binding to PKC‐δ. Likewise, the inhibition of PKCδ ameliorated Van‐induced apoptosis in human kidney‐2 cells and kidney tissues. Furthermore, the data showed that PT‐Atg7‐KO exerted a renoprotective effect against Van‐induced nephrotoxicity, but this effect was lost after injection with myc‐tagged PKCδ. Taken altogether, these results indicate that Van induces autophagy by suppressing the activation of the ERK1/2 and mTOR signaling pathway. In addition, Atg7 mediates Van‐induced AKI through the activation of PKCδ. In sum, autophagy inhibition may serve as a novel therapeutic target for treating nephrotoxic AKI induced by Van.—Xu, X., Pan, J., Li, H., Li, X., Fang, F., Wu, D., Zhou, Y., Zheng, P., Xiong, L., Zhang, D. Atg7 mediates renal tubular cell apoptosis in vancomycin nephrotoxicity through activation of PKC‐δ. FASEB J. 33, 4513–4524 (2019). http://www.fasebj.org