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Zearalenone (ZEA) is a ubiquitous mycotoxin contaminant that causes immune toxicity, apoptosis, and oxidative stress in animals. Hyperoside (Hyp) is a flavonol glycoside compound with antioxidant and anti-apoptotic properties. However, the potential of Hyp to prevent ZEA-induced spleen injury remains unknown. To evaluate the chemoprotective effect of Hyp against ZEA-induced spleen injury, 60 male Kunming mice were randomly assigned into five groups. The first two groups were orally treated with ZEA (40 mg/kg) for 30 days, and combined with Hyp (0, 100 mg/kg) treatment. The other three groups are orally treated with normal saline, olive oil, or Hyp (100 mg/kg) for 30 days. Hyperoside had an inhibitory effect against ZEA-induced spleen lesions. In addition, Hyp significantly increased the activity of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT)], the total antioxidant capacity (T-AOC), and significantly reduced the malondialdehyde (MDA) content reducing ZEA-induced oxidative stress in the spleen. Moreover, the translation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes (CAT, NQO1, SOD1, GSS, GCLM, and GCLC) were ameliorated using co-therapy with Hyp before treatment with ZEA. Hyperoside also significantly inhibited the translation and expression of apoptotic genes (caspase3, casepase9, Bax, Bcl-2) and the production of apoptotic bodies induced by ZEA in the spleen. In conclusion, the findings revealed that Hyp inhibited ZEA-induced spleen injury through its antioxidant and anti-apoptotic effects. Thus, it provides a new treatment option for immune system diseases caused by ZEA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cadmium is an environmental metal pollutant that has been a focus of research in recent years, which is reported to cause bone disease; however, its skeletal toxicity and the mechanism involved are not yet fully known. Therefore, this study used MC3T3-E1 subclone 14 cells to determine the mechanism of cadmium toxicity on bone. Cadmium chloride (Cd) significantly reduced cell viability in a concentration-dependent manner. Exposure to Cd inhibited osteoblast-related proteins (Runx2, Col-1, STC2) and decreased alkaline phosphatase (ALP) activity. Cd caused Exportin-1 accumulation and induced DNA damage. Cd significantly down-regulated caspase 9 and induced cleaved-PARP, cleaved-caspase 3 protein level. Treatment with JNK inhibitor, SP600125, suppressed cadmium-induced elevation in the ratio of phosphorylation of JNK to JNK. Inhibition of caspase with pan-caspase inhibitor, Z-VAD-FMK, prevented MC3T3-E1 subclone 14 cells from cadmium-induced reduction of Runx2, STC2, caspase 9, and accumulation of cleaved PARP and cleaved caspase 3. Cd-induced cell survival enhanced by SP600125 but rescued by Z-VAD-FMK or KPT-335. These results suggest that cadmium cytotoxicity on bone involved exportin 1 accumulation, phosphorylation of JNK, induction of DNA damage and pro-apoptosis, which was induced by activation of caspase-dependent pathways., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The role of estrogen receptor β (ERβ) in bone health is closely associated with its function in vivo, and ERβ−/− mice have been widely utilized to explore the related influences. In this study, ERβ−/− female mice were established to investigate the differential expression of circular RNAs (circRNAs) by RNA-Sequencing (RNA-Seq). Among these circRNAs, mmu_circ_0011379 (named Circ-Spen) exhibited high expression in ERβ−/− female mice. However, the precise mechanism by which Circ-Spen regulates bone health remained unclear. This study identified Circ-Spen as a positive regulator of mouse bone marrow mesenchymal stem cell (mBMSC) viability. The expression of Circ-Spen was markedly increased in ERβ−/− mice femurs tested by RT-qPCR. Moreover, Circ-Spen exhibited an enhanced expression during the bone formation process of mBMSCs. Qualitative experiments also demonstrated that Circ-Spen possessed a circular structure and was localized within the nucleus of mBMSCs. Functionally, it inhibited apoptosis via caspase-3, BCL-2, and BAX, while also promoting autophagy through BECN1 and P62 in mBMSCs tested by MTT assays, transmission electron microscopy (TEM), and Western blotting. These findings reveal the potential of targeting Circ-Spen as a promising therapeutic strategy for rejuvenating senescent mBMSCs and enhancing the efficiency of mBMSC transplantation, which lays the foundation for advancements in the field of bone therapy. [ABSTRACT FROM AUTHOR]

For commercial aquatic animals, hypoxia phenomenon often occurs in live transport and aquaculture. In previous studies, much interest has been focused on antioxidant enzyme activities and could not present the complexities. The multifaceted responses, especially considering physiological indexes, histological structure, cell apoptosis, and immune pathways, are still unknown. In this study, we investigated the comprehensive hypoxic responses of Marsupenaeus japonicus. The results showed that the physiological indexes showed time-dependent changes upon hypoxia stress. Hypoxia stress led to significant tissue damage and cell apoptosis in the gill and hepatopancreas. Compared with the control group, the apoptosis index (AI) of the 12 h hypoxic treatment increased significantly (p < 0.05) in the gills and hepatopancreas. Comparative transcriptome analysis identified 900 and 1400 differentially expressed genes (DEGs) in the gill and hepatopancreas, respectively. Several DEGs were related to the lysosome, glycolysis/gluconeogenesis, citrate cycle, and apoptosis, and seven of them were validated using quantitative real-time PCR. This study provided valuable clues to understanding the mechanisms underlying the hypoxic responses of M. japonicus. • The physiological indexes showed time-dependent changes upon hypoxia stress. • Hypoxia stress led to significant tissue damage and cell apoptosis. • A total of 900 and 1400 DEGs were detected in the gill and hepatopancreas. • Glycolysis, anaerobic metabolism and TCA cycle were affected by hypoxia stress. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) lacks a recognized therapeutic molecular target and has an unfavorable prognosis. (20S)-Protopanaxatriol (g-PPT, PPT) is an active metabolite extracted from ginseng. Accumulating evidence suggests that it has good anti-cancer activity in vivo and in vitro. In this study, we aimed to elucidate the anti-tumor effects of PPT in TNBC cells and tumor-bearing mice, as well as the relevant molecular mechanisms of autophagy and apoptosis. In vitro , we have found that PPT is capable of inducing non-protective autophagy and apoptosis, thus exerting some anti-proliferative and anti-migration activity in TNBC cells. And in vivo , the therapeutic effects of PPT were evaluated by xenograft mouse models. The potential binding mode of PPT and Akt was predicted by molecular docking. Our findings indicated that PPT treatment induced non-protective autophagy in TNBC cells by inhibiting the Akt/mTOR signaling pathway. Therefore, PPT may be a potential treatment for TNBC in the future. • PPT exerted anti-cancer effect in TNBC cells both in vitro and in vivo. • PPT activates apoptosis and non-protective autophagy in TNBC cells. • PPT activates apoptosis and autophagy by inhibiting Akt/mTOR pathway in TNBC cells. [ABSTRACT FROM AUTHOR]

In this study, a series of novel naphthalimide-benzotriazole conjugates (1a – 3c) based on 1, 8-naphthalimide as a core skeleton, aiming at G-quadruplexes, were designed and synthesized, and their anti-cancer activity and mechanism were studied. Using the CCK-8 assay, FRET melting, EMSA, CD, and molecular docking, intracellular assays, western blotting, immunofluorescence, and flow cytometry. By the CCK-8 assay, it was found that the compound, 2-(3-(piperazin-1-yl)propyl)-6-(1H-benzo [d][1,2,3]triazol-1-yl)-1 H -benzo[ de ]isoquinoline-1,3(2 H)-dione (3a), has better activity against A549 cells. Through extracellular assays, including FRET melting, EMSA, CD, and molecular docking, results showed that 3a selectively interacted with BCL2 G-quadruplex(es). Further studies by intracellular assays, including western blotting, immunofluorescence, flow cytometry, etc., verified that 3a mediated the death of A549 cells by two pathways: inhibition of the expression of the BCL2 gene, causing tumor cell apoptosis, and promotion of genetic instability, causing autophagy. This study suggests that the type of compounds, in particular, 3a , may be a potential molecule to explore for BCL2 G-quadruplex-targeted drugs against lung cancer. Our findings demonstrate that compound 3a as a BCL2 G-quadruplex ligand induces DNA damage, autophagy, and apoptosis in A549 cells. This study provides us with a type of lead compound as an anti-tumor drug. [Display omitted] • 9 novel naphthalimide-benzotriazole conjugates were synthesized. • 3a showed the strongest inhibitory activity against A549 cells. • 3a stabilized Bcl-2 G-quadruplexes and induced apoptosis and autophagic cell death. [ABSTRACT FROM AUTHOR]