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The UMB Digital Archive is a service of the Health Sciences and Human Services Library (HS/HSL) that collects, preserves, and distributes the academic works of the University of Maryland, Baltimore. It is a place that digitally captures the historical record of the campus.
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NQO1 protects obese mice through improvements in glucose and lipid metabolismChronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes to energy metabolism regulation. Here, inducible activation of Nrf2 in mice and transgenesis of the Nrf2 target, NQO1, conferred protection from diet-induced metabolic defects through preservation of glucose homeostasis, insulin sensitivity, and lipid handling with improved physiological outcomes. NQO1-RNA interaction mediated the association with and inhibition of the translational machinery in skeletal muscle of NQO1 transgenic mice. NQO1-Tg mice on high-fat diet had lower adipose tissue macrophages and enhanced expression of lipogenic enzymes coincident with reduction in circulating and hepatic lipids. Metabolomics data revealed a systemic metabolic signature of improved glucose handling, cellular redox, and NAD+ metabolism while label-free quantitative mass spectrometry in skeletal muscle uncovered a distinct diet- and genotype-dependent acetylation pattern of SIRT3 targets across the core of intermediary metabolism. Thus, under nutritional excess, NQO1 transgenesis preserves healthful benefits.
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Integrated analysis of microRNA and mRNA expression profiles in Crassostrea gigas to reveal functional miRNA and miRNA-targets regulating shell pigmentation.MicroRNAs (miRNAs) regulate post-transcription gene expression by targeting genes and play crucial roles in diverse biological processes involving body color formation. However, miRNAs and miRNA-targets underlying shell color polymorphism remain largely unknown in mollusca. Using four shell colors full-sib families of the Pacific oyster Crassostrea gigas, we systematically identified miRNAs and miRNA-targets in the mantles, which organ could produce white, golden, black or partially pigmented shell. RNA sequencing and analysis identified a total of 53 known miRNA and 91 novel miRNAs, 47 of which were detected to differentially express among six pairwise groups. By integrating miRNA and mRNA expression profiles, a total of 870 genes were predicted as targets of differentially expressed miRNAs, mainly involving in biomineralization and pigmentation through functional enrichment. Furthermore, a total of four miRNAs and their target mRNAs were predicted to involve in synthesis of melanin, carotenoid or tetrapyrrole. Of them, lgi-miR-317 and its targets peroxidase and lncRNA TCONS_00951105 are implicated in acting as the competing endogenous RNA to regulate melanogenesis. Our studies revealed the systematic characterization of miRNAs profiles expressed in oyster mantle, which might facilitate understanding the intricate molecular regulation of shell color polymorphism and provide new insights into breeding research in oyster.
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Extracellular vesicles from young women's breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach.Background: Extracellular vesicles (EVs) are small membrane particles that contribute to cancer progression and metastases by transporting biologically significant proteins and nucleic acids. They may also serve as biomarkers of various disease states or important therapeutic targets. Breast cancer EVs have the potential to change the behavior of other cells in their microenvironment. However, the proteomic content of EVs isolated from young women’s breast cancer patients and the mechanisms underlying the influence of EVs on tumor cell behavior have not yet been reported. Methods: In our current translational studies, we compared the proteomic content of EVs isolated from invasive breast cancer cell lines and plasma samples from young women’s breast cancer (YWBC) patients and age-matched healthy donors using mass spectrometry. We analyzed the functionality of EVs in two dimensional tumor cell invasion assays and the gene expression changes in tumor cells after incubation with EVs. Results: We found that treatment with EVs from both invasive breast cancer cell lines and plasma of YWBC patients altered the invasive properties of non-invasive breast cancer cells. Proteomics identified differences between EVs from YWBC patients and healthy donors that correlated with their altered function. Further, we identified gene expression changes in non-invasive breast cancer cells after treatment with EVs that implicate the Focal Adhesion Kinase (FAK) signaling pathway as a potential targetable pathway affected by breast cancer-derived EVs. Conclusions: Our results suggest that the proteome of EVs from breast cancer patients reflects their functionality in tumor motility assays and may help elucidate the role of EVs in breast cancer progression.