The prognostic significance and immune correlation of SLC10A3 in low-grade gliomas revealed by bioinformatic analysis and multiple immunohistochemistry.

PURPOSE: Despite the fact that genetic risk factors contribute to low-grade gliomas (LGGs), the role of critical genes as prognostic and theraputic biomarkers is quite limited. This study is designed to comprehensively investigate the prognostic role and predictive ability of solute carrier family 10 member 3 (SLC10A3) for immunotherapy in LGGs. METHODS: We analyzed the prognostic value of SLC10A3 from multiple datasets of LGG patients, and explored its immune correlation via multiple algorithms. Finally, we independently confirmed the clinical significance and its immune correlation using the multiplex staining assay of LGG samples on the tissue microarray. RESULTS: SLC10A3 mRNA was up-regulated in LGGs compared with normal brain tissues, and correlated with tumor grade, histological type, IDH wide type and non-codel 1p19q. Up-regulation of SLC10A3 transcription was remarkably associated with shortened overall survival time compared with down-regulation in TCGA, CGGA and Rembrandt datasets, and SLC10A3 exhibited good predictive ability for survival outcomes among LGGs. Correlation analyses showed that SLC10A3 mRNA expression correlates well with the six immune check points and immune cells. When the expression and immune correlation of SLC10A3 at the translational level were verified via multiplex immunohistochemistry, expression of SLC10A3 protein was higher in LGG compared with normal tissues, and expression of SLC10A3 protein was correlated well with macrophage, CD4 + T cell and B cell. CONCLUSIONS: Up-regulation of SLC10A3 mRNA is statistically associated with adverse survival outcomes and immune infiltration among LGGs. SLC10A3 might be a reliable survival predictor and a promising immunotherapy target for LGG patients.

Deoxynivalenol and zearalenone: Different mycotoxins with different toxic effects in donkey (Equus asinus) endometrial epithelial cells.

Deoxynivalenol (DON) and zearalenone (ZEA), which are commonly found in feed products, exhibit serious negative effects on the reproductive systems of domestic animals. However, the toxicity of mycotoxins on the uterine function of donkey (Equus asinus) remains unclear. This study investigated the biological effects of DON and ZEA exposure on donkey endometrial epithelial cells (EECs). It was administered 10 µM and 30 µM DON and ZEA to cells cultured in vitro. The results showed that 10 µM DON exposure markedly changed the expression levels of pyroptosis-associated genes and that 30 µM ZEA exposure changed the expression levels of inflammation-associated genes in EECs. The mRNA expression of cancer-promoting genes was markedly upregulated in cells exposed to DON and 30 µM ZEA; in particular, 10 µM and 30 µM DON and ZEA markedly disturbed the expression of androgen and estrogen secretion-related genes. Furthermore, Q-PCR, Western blot, and immunofluorescence analyses verified the different expression patterns of related genes in DON- and ZEA-exposed EECs. Collectively, these results illustrated the impact of exposure to different toxins and concrete toxicity on the mRNA expression of EECs from donkey in vitro.

Deoxynivalenol and Zearalenone: Different Mycotoxins with Different Toxic Effects in the Sertoli Cells of Equus asinus.

(1) Background: Deoxynivalenol (DON) and zearalenone (ZEA) are type B trichothecene mycotoxins that exert serious toxic effects on the reproduction of domestic animals. However, there is little information about the toxicity of mycotoxins on testis development in Equus asinus. This study investigated the biological effects of DON and ZEA exposure on Sertoli cells (SCs) of Equus asinus; (2) Methods: We administered 10 µM and 30 µM DON and ZEA to cells cultured in vitro; (3) Results: The results showed that 10 µM DON exposure remarkably changed pyroptosis-associated genes and that 30 µM ZEA exposure changed inflammation-associated genes in SCs. The mRNA expression of cancer-promoting genes was remarkably upregulated in the cells exposed to DON or 30 µM ZEA; in particular, DON and ZEA remarkably disturbed the expression of androgen and oestrogen secretion-related genes. Furthermore, quantitative RT-PCR, Western blot, and immunofluorescence analyses verified the different expression patterns of related genes in DON- and ZEA-exposed SCs; (4) Conclusions: Collectively, these results illustrated the impact of exposure to different toxins and concrete toxicity on the mRNA expression of SCs from Equus asinus in vitro.

Zearalenone Exposure Enhanced the Expression of Tumorigenesis Genes in Donkey Granulosa Cells via the PTEN/PI3K/AKT Signaling Pathway.

Zearalenone (ZEA) is a natural contaminant existing in food and feed products that exhibits a negative effect on domestic animals' reproduction. Donkeys possess high economic value in China and are at risk of exposure to ZEA. However, few information is available on ZEA-induced toxicity and no report on toxicity in donkeys can be found in scientific literature. We investigated the biological effects of ZEA exposure on donkey granulosa cells (dGCs) by using RNA-seq analysis. ZEA at 10 and 30 µM were administered to GCs within 72 h of in vitro culture. ZEA at 10 µM significantly altered the tumorigenesis associated genes in dGCs. Exposure to 10 and 30 µM ZEA treatment significantly reduced mRNA expression of PTEN, TGFß, ATM, and CDK2 genes, particularly, the ZEA treatment significantly increased the expression of PI3K and AKT genes. Furthermore, immunofluorescence, RT-qPCR, and Western blot analysis verified the gene expression of ZEA-exposed GCs. Collectively, these results demonstrated the deleterious effect of ZEA exposure on the induction of ovarian cancer related genes via the PTEN/PI3K/AKT signaling pathway in dGCs in vitro.

Differentiation of sow and mouse ovarian granulosa cells exposed to zearalenone in vitro using RNA-seq gene expression.

Zearalenone (ZEA), a natural contaminant found in feed, has been shown to have a negative impact on domestic animal reproduction, particularly in pigs. There are species-specific differences in the ZEA-induced toxicity pattern. Here, we investigated the different biological effects of ZEA exposure on porcine and mouse granulosa cells, using RNA-seq analysis. We treated murine and porcine granulosa cells with 10 µM and 30 µM ZEA during 72 h of culturing, in vitro. The results showed that 10 µM ZEA exposure significantly altered mitosis associated genes in porcine granulosa cells, while the same treatment significantly altered the steroidogenesis associated genes in mouse granulosa cells. Exposure to 30 µM ZEA resulted in significantly up-regulated expression of inflammatory related genes in porcine granulosa cells as well as the cancer related genes in mouse granulosa cells. Similarly, 30 µM ZEA exposure significantly decreased the expression of tumor suppressor factors in the mouse granulosa cells. Furthermore, immunofluorescence, RT-qPCR as well as western-blot analysis verified the different expression of related genes in ZEA exposed porcine and mouse granulosa cells. Collectively, these results illustrate the presence of species differences with regards to ZEA effects between porcine and mouse ovarian granulosa cells, in vitro.