Analysis of ceRNA network of differentially expressed genes in FaDu cell line and a cisplatin-resistant line derived from it

Background Hypopharyngeal cancer accounts for 2% in head and neck cancers and has a poor prognosis. Cisplatin is a widely used chemotherapeutic drug in kinds of carcinomas, concluding hypopharyngeal cancer. However, the resistance of cisplatin appeared in recent years. Cisplatin-resistance has been partly explored before, but rarely in hypopharyngeal cancer. Methods We cultured the hypopharyngeal cancer cell (FaDu) and induced its cisplatin-resistant cell (FaDu/DDP4). Then we tested the differentially expressed genes (DEGs) between FaDu and FaDu/DDP4. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted on the DEGs, and we drew the ceRNA networks of DEGs. Finally, we chose eight miRNAs and six mRNAs for qRT-PCR to verify our microarray. Results We induced cisplatin-resistant FaDu/DDP4 and proved its chemoresistance. The resistance index (RI) of FaDu/DDP4 was 2.828. DEGs contain 2,388 lncRNAs, 1,932 circRNAs, 745 mRNAs and 202 miRNAs. These 745 mRNAs were classified into three domains and 47 secondary GO terms. In KEGG pathway enrichment, the “TNF signaling pathway”, “IL-17 signaling pathway” and “JAK-STAT signaling pathway” were potentially significant signaling pathways. Then, 52 lncRNAs, 148 circRNAs, 155 mRNAs and 18 miRNAs were selected to draw the network. We noticed several potential targets (as miR-197-5p, miR-6808-5p, APOE, MMP1, S100A9 and CYP24A1). At last, the eight miRNAs and six mRNAs that are critical RNAs in ceRNA network were verified by qRT-PCR. Conclusion The microarray helped to find DEGs in cisplatin-resistant hypopharyngeal cancer. TNF, IL-17 and JAK-STAT signaling pathways might be more significant for cisplatin-resistance. MiR-197-5p, miR-6808-5p, APOE, MMP1, S100A9 and CYP24A1 might be potential genes inducing resistance

Taxifolin increased semen quality of Duroc boars by improving gut microbes and blood metabolites.

peer reviewedTaxifolin (TAX), as a natural flavonoid, has been widely focused on due to its strong anti-oxidation, anti-inflammation, anti-virus, and even anti-tumor activity. However, the effect of TAX on semen quality was unknown. The purpose of this study was to analyze the beneficial influences of adding feed additive TAX to boar semen in terms of its quality and potential mechanisms. We discovered that TAX increased sperm motility significantly in Duroc boars by the elevation of the protein levels such as ZAG, PKA, CatSper, and p-ERK for sperm quality. TAX increased the blood concentration of testosterone derivatives, antioxidants such as melatonin and betaine, unsaturated fatty acids such as DHA, and beneficial amino acids such as proline. Conversely, TAX decreased 10 different kinds of bile acids in the plasma. Moreover, TAX increased "beneficial" microbes such as Intestinimonas, Coprococcus, Butyrivibrio, and Clostridium_XlVa at the Genus level. However, TAX reduced the "harmful" intestinal bacteria such as Prevotella, Howardella, Mogibacterium, and Enterococcus. There was a very close correlation between fecal microbes, plasma metabolites, and semen parameters by the spearman correlation analysis. Therefore, the data suggest that TAX increases the semen quality of Duroc boars by benefiting the gut microbes and blood metabolites. It is supposed that TAX could be used as a kind of feed additive to increase the semen quality of boars to enhance production performance

Alginate oligosaccharide extends the service lifespan by improving the sperm metabolome and gut microbiota in an aging Duroc boars model.

peer reviewed[en] INTRODUCTION: Alginate oligosaccharide (AOS), as a natural non-toxic plant extract, has been paid more attention in recent years due to its strong antioxidant, anti-inflammatory, and even anti-cancer properties. However, the mechanism by which AOS affects animal reproductive performance is still unclear. METHODS: The purpose of this study is to use multi-omics technology to analyze the effects of AOS in extending the service lifespan of aging boars. RESULTS: The results showed that AOS can significantly improve the sperm motility (p < 0.05) and sperm validity rate (p < 0.001) of aging boars and significantly reduce the abnormal sperm rate (p < 0.01) by increasing the protein levels such as CatSper 8 and protein kinase A (PKA) for semen quality. At the same time, AOS significantly improved the testosterone content in the blood of boars (p < 0.01). AOS significantly improved fatty acids such as adrenic acid (p < 0.05) and antioxidants such as succinic acid (p < 0.05) in sperm metabolites, significantly reducing harmful substances such as dibutyl phthalate (p < 0.05), which has a negative effect on spermatogenesis. AOS can improve the composition of intestinal microbes, mainly increasing beneficial bacteria Enterobacter (p = 0.1262) and reducing harmful bacteria such as Streptococcus (p < 0.05), Prevotellaceae_UCG-001 (p < 0.05), and Prevotellaceae_NK3B31_group (p < 0.05). Meanwhile, short-chain fatty acids in feces such as acetic acid (p < 0.05) and butyric acid (p < 0.05) were significantly increased. Spearman correlation analysis showed that there was a close correlation among microorganisms, sperm metabolites, and sperm parameters. DISCUSSION: Therefore, the data indicated that AOS improved the semen quality of older boars by improving the intestinal microbiota and sperm metabolome. AOS can be used as a feed additive to solve the problem of high elimination rate in large-scale boar studs

Hydroxytyrosol Benefits Boar Semen Quality via Improving Gut Microbiota and Blood Metabolome.

peer reviewedSemen quality is one of the most important factors for the success of artificial insemination which has been widely applied in swine industry to take the advantages of the superior genetic background and higher fertility capability of boars. Hydroxytyrosol (HT), a polyphenol, has attracted broad interest due to its strong antioxidant, anti-inflammatory, and antibacterial activities. Sperm plasma membrane contains a large proportion of polyunsaturated fatty acids which is easily impaired by oxidative stress and thus to diminish semen quality. In current investigation, we aimed to explore the effects of dietary supplementation of HT on boar semen quality and the underlying mechanisms. Dietary supplementation of HT tended to increase sperm motility and semen volume/ejaculation. And the follow-up 2 months (without HT, just basal diet), the semen volume was significantly more while the abnormal sperm was less in HT group than that in control group. HT increased the "beneficial microbes" Bifidobacterium, Lactobacillus, Eubacterium, Intestinimonas, Coprococcus, and Butyricicoccus, however, decreased the relative abundance of "harmful microbes" Streptococcus, Oscillibacter, Clostridium_sensu_stricto, Escherichia, Phascolarctobacterium, and Barnesiella. Furthermore, HT increased plamsa steroid hormones such as testosterone and its derivatives, and antioxidant molecules while decreased bile acids and the derivatives. All the data suggest that HT improves gut microbiota to benefit plasma metabolites then to enhance spermatogenesis and semen quality. HT may be used as dietary additive to enhance boar semen quality in swine industry

Alginate oligosaccharides increase boar semen quality by affecting gut microbiota and metabolites in blood and sperm.

peer reviewedAlginate oligosaccharides (AOS), natural polymers from brown seaweeds (such as Laminaria japonica, Undaria pinnatifida, and Sargassum fusiforme), have been reported to possess many beneficial advantages for health. In the current study, after 9 weeks of dietary supplementation, AOS 10 mg/kg group (AOS 10) group increased boar sperm motility from 87.8% to 93.5%, p < 0.05. Moreover, AOS10 increased the relative abundances of Bifidobacterium, Coprococcus, Butyricicoccus (1.3-2.3-fold; p < 0.05) to increase the beneficial blood and sperm metabolites (1.2-1.6-fold; p < 0.05), and important sperm proteins such as gelsolin, Zn-alpha2 glycoprotein, Cation Channel Sperm-Associated Protein, outer dense fiber of sperm tails, etc. (1.5-2.2-fold; p < 0.05). AOS had a long-term beneficial advantage on boar semen quality by the increase in semen volume (175 vs. 160 ml/ejaculation, p < 0.05). AOS may be used as dietary additives for improving semen quality

Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions.

Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing. All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5-20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden. This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.All SEQC2 participants freely donated their time, reagents, and computing resources for the completion and analysis of this project. Part of this work was carried out with the support of the Intramural Research Program of the National Institutes of Health (to Mehdi Pirooznia), National Institute of Environmental Health Sciences (to Pierre Bushel), and National Library of Medicine (to Danielle Thierry-Mieg, Jean Thierry-Mieg, and Chunlin Xiao). Leming Shi and Yuanting Zheng were supported by the National Key R&D Project of China (2018YFE0201600), the National Natural Science Foundation of China (31720103909), and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01). Donald J. Johann, Jr. acknowledges the support by FDA BAA grant HHSF223201510172C. Timothy Mercer and Ira Deveson were supported by the National Health and Medical Research Council (NHMRC) of Australia grants APP1108254, APP1114016, and APP1173594 and Cancer Institute NSW Early Career Fellowship 2018/ECF013. This research has also been, in part, financially supported by the MEYS of the CR under the project CEITEC 2020 (LQ1601), by MH CR, grant No. (NV19-03-00091). Part of this work was carried out with the support of research infrastructure EATRIS-CZ, ID number LM2015064, funded by MEYS CR. Boris Tichy and Nikola Tom were supported by research infrastructure EATRIS-CZ, ID number LM2018133 funded by MEYS CR and MEYS CR project CEITEC 2020 (LQ1601).S