Transcriptome Profiling and Metagenomic Analysis Help to Elucidate Interactions in an Inflammation-Associated Cancer Mouse Model.
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ABSTRACT:
SUBMITTER: Sakai K
PROVIDER: S-EPMC8345192 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a severe clinical syndrome characterized to describe patients with both asthma and COPD clinical characteristics, which has posed a serious threat to patients' quality of life and life safety. However, there are many difficulties and uncertainties in its diagnosis and treatment in clinic; especially, its animal model has not been fully and thoroughly established, and the evaluation of therapeutic drugs is still in its infancy. Here, we used ovalbumin (OVA), lipopolysaccharide (LPS), and smoke costimulation to establish an ACO mouse model and then used RNA-seq technology to detect gene expression in mouse lung tissue. The results showed that ACO mice showed an overlap syndrome of asthma and COPD in lung histological changes and the levels of inflammatory cytokines in bronchoalveolar lavage fluid. The RNA-seq analysis results showed that 6,324 differentially expressed genes (DEGs) were screened between the ACO group and the control group, of which 2,717 (42.7%) were downregulated, and 3,607 (57.3%) were upregulated. Metascape analysis results showed that in the ACO model we established, due to the damage of the respiratory system, the accumulated diseased tissue involves lung, spleen, blood, bone marrow, thymus, etc. It has certain characteristics of pneumonia, pulmonary fibrosis, and chronic obstructive airway disease, lung tumors, rheumatoid arthritis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were enriched in inflammation, immune system activation and imbalance, cell proliferation, and adhesion migration, and the upstream signaling pathways of inflammation were mainly affected by HLA-DRA, SYK, CTLA4, VAV1, NRAS, and JAK3. In short, our research established a mouse model that can better simulate the clinicopathological characteristics of ACO and suggested the foundations in elucidating the molecular mechanisms for pulmonary inflammation and fibrosis in ACO. This work may help further research and contribute substantially to prevention and clinical treatment of ACO in the future.
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Project description:Passion fruit (Passiflora edulia Sims), an important tropical and subtropical species, is classified as a respiration climacteric fruit, and its quality deteriorates rapidly after harvest. To elucidate the mechanisms involved in ripening and rapid fruit senescence, phytochemical characteristic analysis and RNA sequencing were performed in purple passion fruit with different treatments, that is, 1-methylcyclopropene (1-MCP) and preservative film (PF). Comprehensive functional annotation and KEGG enrichment analysis showed that starch and sucrose metabolism, plant hormone signal transduction, phenylpropanoid biosynthesis, flavonoid biosynthesis, and carotenoid biosynthesis were involved in fruit ripening. Treatment with PF and 1-MCP significantly affected the transcription levels of passion fruit during postharvest storage. A large number of differentially expressed unigenes (DEGs) were identified as significantly enriched in starch and sucrose metabolism, plant hormone signal transduction and phenylpropanoid biosynthesis at the postharvest stage. The PF and 1-MCP treatments increased superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) gene expression levels and enzyme activities, accelerated lignin accumulation, and decreased β-galactosidase (β-Gal), polygalacturonase (PG) and cellulose activities and gene expression levels to delay cell wall degradation during fruit senescence. The RNA sequencing data for cell wall metabolism and hormone signal transduction pathway-related unigenes were verified by RT-qPCR. The results of this study indicate that the cell wall metabolism and hormone signaling pathways are closely related to passion fruit ripening. PF and 1-MCP treatment might inhibit ethylene signaling and regulate cell wall metabolism pathways to inhibit cell wall degradation. Our results demonstrate the involvement of ripening- and senescence-related networks in passion fruit ripening and may establish a foundation for future research investigating the effects of PF and 1-MCP treatment on fruit ripening.
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