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Background: Diabetic nephropathy (DN) is a complication caused by diabetes. Circular RNAs (circRNAs) are a kind of RNA with a closed circular structure, which has high stability and is involved in many disease‐related processes. The mechanism of circRNA TAO kinase 1 (circTAOK1) in the pathogenesis and development of DN is unclear. Methods: CircTAOK1, microRNA (miR)‐142‐3p, and sex‐determining region Y‐box transcription factor 6 (SOX6) mRNA levels were analyzed by real‐time quantitative polymerase chain reaction (RT‐qPCR). Cell counting kit‐8 (CCK8) and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays were used to analyze cell proliferation. Cell cycle distribution was detected by flow cytometry. Western blot assay was performed to test B‐cell lymphoma 2 (Bcl‐2), Bcl‐2 associated X (Bax), cleaved‐caspase 3, and fibronectin (FN), collagen I (Col I), and collagen IV (Col IV) protein levels. ELISA assay was used to measure interleukin 1β (IL‐1β), interleukin 6 (IL‐6), and tumor necrosis factor (TNF‐α) levels. The reactive oxygen species (ROS) and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) activity were assessed by the corresponding kits. And the correlation between miR‐142‐3p and circTAOK1 or SOX6 was confirmed by dual luciferase reporter assay, RNA immunoprecipitation assay and RNA pull down assay. Results: CircTAOK1 and SOX6 expression levels were up‐regulated, while miR‐142‐3p expression was down‐regulated in DN serum and HG‐treated HK‐2 cells. Knockdown of circTAOK1 could inhibit cell injury of HG‐induced HK‐2 cells. The inhibitory effect of circTAOK1 knockdown on HG‐induced HK‐2 cell injury was restored by miR‐142‐3p downregulation. CircTAOK1 acted as a sponge for miR‐142‐3p, and SOX6 was targeted by miR‐142‐3p. The overexpression of SOX6 could recover the effect of miR‐142‐3p overexpression on HG‐induced HK‐2 cell injury. CircTAOK1 regulated the expression of SOX6 by targeting miR‐142‐3p. Conclusion: CircTAOK1 knockdown inhibited HG‐induced HK‐2 cell damage in DN by the miR‐142‐3p/SOX6 axis. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Previous studies have shown that circular ribonucleic acid mediates the occurrence of diabetic nephropathy. This study aimed to analyze the effects of circ_0068087 on high‐glucose (HG)‐induced human kidney 2 (HK2) cell dysfunction. Materials and Methods: Circ_0068087, miR‐580‐3p, and progestin and adipoQ receptor 3 (PAQR3) expression were detected by quantitative reverse transcription polymerase chain reaction. Cell viability and proliferation were investigated by Cell Counting Kit‐8 and EdU assays, respectively. The cell apoptotic rate was assessed by flow cytometry. Inflammatory response was assessed by enzyme‐linked immunoassays. Oxidative stress was evaluated by a superoxide dismutase activity assay kit and lipid peroxidation malondialdehyde assay kit. Molecular interaction was identified by dual‐luciferase reporter assay. Results: Circ_0068087 and PAQR3 expression were significantly upregulated in diabetic nephropathy patients. HG treatment inhibited HK2 cell proliferation, but induced cell apoptosis, inflammation, oxidative stress and epithelial–mesenchymal transition by regulating circ_0068087. Circ_0068087 acted as a microribonucleic acid‐580‐3p (miR‐580‐3p) sponge, and miR‐580‐3p targeted PAQR3. Furthermore, circ_0068087 depletion repressed PAQR3 expression through miR‐580‐3p. MiR‐580‐3p inhibitors or PAQR3 introduction attenuated circ_0068087 silencing mediated‐effects in HG‐treated HK2 cells. Conclusion: Circ_0068087 promoted HG‐induced HK2 cell injuries by the regulation of the miR‐580‐3p/PAQR3 pathway. [ABSTRACT FROM AUTHOR]

It is very important to evaluate the immunotoxicity and molecular mechanisms of pesticides. In this study, difenoconazole and chlorothalonil were evaluated for immunotoxicity by using the human Jurkat T-cell line, and the EC50 were 24.66 and 1.17 mg/L, respectively. The joint exposure of difenoconazole and chlorothalonil showed a synergistic effect at low concentrations (lower than 10.58 mg/L) but an antagonistic effect at high concentrations (higher than 10.58 mg/L). With joint exposure at a concentration of EC10, the proportion of late apoptotic cells was 2.26- and 2.91-fold higher than that with exposure to difenoconazole or chlorothalonil alone, respectively. A transcriptomics analysis indicated that the DEGs for single exposure are associated with immunodeficiency disease. Single exposure to chlorothalonil was mainly involved in cation transportation, extracellular matrix organization, and leukocyte cell adhesion. Single exposure to difenoconazole was mainly involved in nervous system development, muscle contraction, and immune system processes. However, when the joint exposure dose was EC10, the DEGs were mainly involved in the formation of cell structures, but the DEGs were mainly involved in cellular processes and metabolism when the joint exposure dose was EC25. The results indicated that the immunotoxicological mechanisms underlying joint exposure to difenoconazole and chlorothalonil are different under low and high doses. [ABSTRACT FROM AUTHOR]

Chemical investigation of the edible mushroom Sarcomyxa edulis led to the isolation of one new highly degraded sterol (1), and one new β-carboline alkaloid (2), along with nine known compounds (3-11) for the first time from this mushroom. The structures of new compounds were elucidated using HR-ESI-MS data and NMR spectroscopy. In addition, anti-inflammatory activity of new compounds was evaluated against lipopolysaccharide-induced NO production in RAW 264.7 macrophages. Compound 2 exhibited a good anti-inflammatory activity with IC50 value of 9.88 ± 0.48 μM, and compound 1 exhibited a weak inhibitory effect with IC50 value of 71.36 ± 5.11 μM. [ABSTRACT FROM AUTHOR]