Molecular, Genetic, and Biochemical Nutrition Commons^™

Critical Contributions Of Protein Cargos To The Functions Of Macrophage‑Derived Extracellular Vesicles, Baolong Liu, Phuong Linh Nguyen, Han Yu, Xingzhi Li, Huiren Wang, Wang Price, Meng Niu, Chittibabu Guda, Xiao Cheng, Xinghui Sun, Regis Moreau, Amanda E. Ramer-Tait, Michael J. Naldrett, Sophie Alvarez, Jiujiu Yu

Department of Nutrition and Health Sciences: Faculty Publications

Background Macrophages are highly plastic innate immune cells that play key roles in host defense, tissue repair, and homeostasis maintenance. In response to divergent stimuli, macrophages rapidly alter their functions and manifest a wide polarization spectrum with two extremes: M1 or classical activation and M2 or alternative activation. Extracellular vesicles (EVs) secreted from differentially activated macrophages have been shown to have diverse functions, which are primarily attributed to their microRNA cargos. The role of protein cargos in these EVs remains largely unexplored. Therefore, in this study, we focused on the protein cargos in macrophage-derived EVs.

Results Naïve murine bone marrow-derived …

Editorial: Inter-Organ Crosstalk During Exercise In Health And Disease: Extracellular Vesicles As New Kids On The Block, Kenneth Verboven, Ivan Jose Vechetti Jr

Department of Nutrition and Health Sciences: Faculty Publications

Within exercise physiology, the study of factors potentially mediating interorgan crosstalk during and after exercise is a fascinating field of research. As exercise activates a plethora of metabolic pathways in several tissues, organs and systems, examining the underlying biological mechanisms contributing to exercise related metabolic benefits is imperative. Since two decades, the skeletal muscle is known to secrete humoral factors into the circulation in response to exercise, originally described as “myokines” by Pedersen et al. (2003). These myokines are now well known and extensively studied in the field of exercise science (Pedersen and Febbraio, 2012). Interestingly, exercise also triggers other …

Extracellular Vesicle Characteristics And Micro Rna Content In Cerebral Palsy And Typically Developed Individuals At Rest And In Response To Aerobic Exercise., Ivan Jose Vechetti Jr, Jessica Norrbom, Björn Alkner, Emma Hjalmarsson, Alexandra Palmcrantz, Eva Pontén, Jessica Pingel, Ferdinand Von Walden, Rodrigo Fernandez-Gonzalo

Department of Nutrition and Health Sciences: Faculty Publications

In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45 min of cycling (n = 10; TD EX) or were enrolled as controls with no exercise (n = 10; TD CON). Blood was drawn before and 30 min after exercise and analyzed for EV concentration, size, and microRNA …

Identification Of Anti-Inflammatory Vesicle-Like Nanoparticles In Honey, Xingyi Chen, Boalong Liu, Xingzhi Li, Thuy T. An, You Zhou, Gang Li, Judy Wu-Smart, Sophie Alvarez, Michael J. Naldrett, James Eudy, Gregory Kubik, Richard A. Wilson, Stephen D. Kachman, Juan Cui, Jiujiu Yu

Department of Nutrition and Health Sciences: Faculty Publications

Honey has been used as a nutrient, an ointment, and a medicine worldwide for many centuries. Modern research has demonstrated that honey has many medicinal properties, reflected in its anti-microbial, anti-oxidant, and anti-inflammatory bioactivities. Honey is composed of sugars, water and a myriad of minor components, including minerals, vitamins, proteins and polyphenols. Here, we report a new bioactive component‒vesicle-like nanoparticles‒in honey (H-VLNs). These HVLNs are membrane-bound nano-scale particles that contain lipids, proteins and small-sized RNAs. The presence of plant-originated plasma transmembrane proteins and plasma membrane-associated proteins suggests the potential vesicle-like nature of these particles. H-VLNs impede the formation and activation …

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 …

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 …

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, …

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 …

Biology Of Exosomes And Their Microrna Cargos In Human And Bovine Milk, Amy Lynn Leiferman

College of Education and Human Sciences: Dissertations, Theses, and Student Research

Exosomes are small, cargo-containing vesicles secreted by cells to facilitate intercellular communication. Of exosome cargos, microRNAs are especially interesting because of their involvement in gene regulation. Recently, our lab has shown that exosomes and their microRNA cargo are absorbed through the diet and elicit effects exogenously. Human and animal milk contain exosomes, which may have implications in infant and adult nutrition. There is evidence that bovine milk exosomes enhance growth of murine C2C12 myotube cell cultures, but whether this translates to muscle in vivo is unknown. The USDA National Nutrient Database for Standard Reference is lacking up-to-date information about human …

Milk Exosomes: Beyond Dietary Micrornas, Janos Zempleni

Department of Nutrition and Health Sciences: Faculty Publications

Extracellular vesicles deliver a variety of cargos to recipient cells, including the delivery of cargos in dietary vesicles from bovine milk to non-bovine species. The rate of discovery in this important line of research is slowed by a controversy whether the delivery and bioactivity of a single class of vesicle cargos, microRNAs, are real or not. This opinion paper argues that the evidence in support of the bioavailability of microRNAs encapsulated in dietary exosomes outweighs the evidence produced by scholars doubting that phenomenon is real. Importantly, this paper posits that the time is ripe to look beyond microRNA cargos and …