Molecular, Genetic, and Biochemical Nutrition Commons^™

Dietary Depletion Of Milk Exosomes And Their Microrna Cargos Elicits A Depletion Of Mir-200a-3p And Elevated Intestinal Inflammation And Chemokine (C-X-C Motif) Ligand 9 Expression In Mdr1a−/− Mice, Di Wu, Hatem Kittana, Jiang Shu, Stephen D. Kachman, Juan Cui, Amanda E. Ramer-Tait, Janos Zempleni

Department of Nutrition and Health Sciences: Faculty Publications

Background: Exosomes transfer regulatory microRNAs (miRs) from donor cells to recipient cells. Exosomes and miRs originate from both endogenous synthesis and dietary sources such as milk. miR-200a-3p is a negative regulator of the proinflammatory chemokine (C-X-C motif) ligand 9 (CXCL9). Male Mdr1a−/− mice spontaneously develop clinical signs of inflammatory bowel disease (IBD).

Objectives: We assessed whether dietary depletion of exosomes and miRs alters the severity of IBD in Mdr1a−/− mice owing to aberrant regulation of proinflammatory cytokines.

Methods: Starting at 5 wk of age, 16 male Mdr1a−/− mice were fed either milk exosome– and RNA-sufficient (ERS) or milk exosome– and …

Inhibitory Effects Of Shiitake-Derived Exosome-Like Nanoparticles On Nlrp3 Inflammasome Activation, Yizhu Lu

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

The NLRP3 inflammasome is a critical mediator of inflammation and consists of the sensor NOD-like receptor family, pyrin domain containing 3 (NLRP3), the adaptor apoptotic speck protein containing a caspase recruitment domain (ASC), and the effector caspase-1. Dysregulated or excessive activation of the NLRP3 inflammasome contributes to pathogenesis of diverse inflammatory diseases such as Type 2 diabetes and atherosclerosis. Therefore, the NLRP3 inflammasome is a promising therapeutic target for treating these diseases. Extracellular vesicles (EVs) are membrane-enclosed tiny particles released by almost any type of cells and they are involved in the intercellular communication by transferring their cargos including RNAs, …

Transport And Distribution Of Bovine Milk Exosomes And Mir-34a Cargo In Murine Cerebral Cortex Endothelial Bend.3 Cells And Bv2 Microglia, Pearl Ebea

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

The blood-brain barrier (BBB) poses an obstacle in the delivery of drugs to the brain. Bovine milk exosomes (BME) are explored for delivering antisense oligonucleotides to tumors, because BME are bioavailable and protect RNA cargos against degradation in the gastrointestinal tract. This study had the following objectives: 1) assess the transport kinetics of BME and their RNA cargos and secretion of RNA across the apical membrane in murine cerebral cortex endothelial bEnd.3 cells and 2) determine whether murine brain BV2 microglia have the potential to accumulate and, therefore, eliminate BME that crossed the BBB. The uptake of BME labeled with …

Milk-Derived Exosomes And Metabolic Regulation, Janos Zempleni, Sonal Sukreet, Fang Zhou, Di Wu, Ezra Mutai

Department of Nutrition and Health Sciences: Faculty Publications

Exosomes are natural nanoparticles that play an important role in cell-to-cell communication. Communication is achieved through the transfer of cargos, such as microRNAs, from donor to recipient cells and binding of exosomes to cell surface receptors. Exosomes and their cargos are also obtained from dietary sources, such as milk. Exosome and cell glycoproteins are crucial for intestinal uptake. A large fraction of milk exosomes accumulates in the brain, whereas the tissue distribution of microRNA cargos varies among distinct species of microRNA. The fraction of milk exosomes that escapes absorption elicits changes in microbial communities in the gut. Dietary depletion of …