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https://www.readbyqxmd.com/read/27852870/biological-activities-of-extracellular-vesicles-and-their-cargos-from-bovine-and-human-milk-in-humans-and-implications-for-infants
#1
REVIEW
Janos Zempleni, Ana Aguilar-Lozano, Mahrou Sadri, Sonal Sukreet, Sonia Manca, Di Wu, Fang Zhou, Ezra Mutai
Extracellular vesicles (EVs) in milk harbor a variety of compounds, including lipids, proteins, noncoding RNAs, and mRNAs. Among the various classes of EVs, exosomes are of particular interest, because cargo sorting in exosomes is a regulated, nonrandom process and exosomes play essential roles in cell-to-cell communication. Encapsulation in exosomes confers protection against enzymatic and nonenzymatic degradation of cargos and provides a pathway for cellular uptake of cargos by endocytosis of exosomes. Compelling evidence suggests that exosomes in bovine milk are transported by intestinal cells, vascular endothelial cells, and macrophages in human and rodent cell cultures, and bovine-milk exosomes are delivered to peripheral tissues in mice...
November 16, 2016: Journal of Nutrition
https://www.readbyqxmd.com/read/27633112/riboflavin
#2
John T Pinto, Janos Zempleni
No abstract text is available yet for this article.
September 2016: Advances in Nutrition
https://www.readbyqxmd.com/read/27041646/inhibition-of-acetyl-coa-carboxylases-by-soraphen-a-prevents-lipid-accumulation-and-adipocyte-differentiation-in-3t3-l1-cells
#3
Elizabeth L Cordonier, Sarah K Jarecke, Frances E Hollinger, Janos Zempleni
Acetyl-CoA carboxylases (ACC) 1 and 2 catalyze the carboxylation of acetyl-CoA to malonyl-CoA and depend on biotin as a coenzyme. ACC1 localizes in the cytoplasm and produces malonyl-CoA for fatty acid (FA) synthesis. ACC2 localizes in the outer mitochondrial membrane and produces malonyl-CoA that inhibits FA import into mitochondria for subsequent oxidation. We hypothesized that ACCs are checkpoints in adipocyte differentiation and tested this hypothesis using the ACC1 and ACC2 inhibitor soraphen A (SA) in murine 3T3-L1 preadipocytes...
June 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/26984735/human-vascular-endothelial-cells-transport-foreign-exosomes-from-cow-s-milk-by-endocytosis
#4
Rio Jati Kusuma, Sonia Manca, Taylor Friemel, Sonal Sukreet, Christopher Nguyen, Janos Zempleni
Encapsulation of microRNAs in exosomes confers protection against degradation and a vehicle for shuttling of microRNAs between cells and tissues, and cellular uptake by endocytosis. Exosomes can be found in foods including milk. Humans absorb cow's milk exosomes and deliver the microRNA cargo to peripheral tissues, consistent with gene regulation by dietary nucleic acids across species boundaries. Here, we tested the hypothesis that human vascular endothelial cells transport milk exosomes by endocytosis, constituting a step crucial for the delivery of dietary exosomes and their cargo to peripheral tissues...
May 15, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/26528912/computational-characterization-of-exogenous-micrornas-that-can-be-transferred-into-human-circulation
#5
Jiang Shu, Kevin Chiang, Janos Zempleni, Juan Cui
MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs...
2015: PloS One
https://www.readbyqxmd.com/read/26478250/glucocorticoid-cell-priming-enhances-transfection-outcomes-in-adult-human-mesenchymal-stem-cells
#6
Abby M Kelly, Sarah A Plautz, Janos Zempleni, Angela K Pannier
Human mesenchymal stem cells (hMSCs) are one of the most widely researched stem cell types with broad applications from basic research to therapeutics, the majority of which require introduction of exogenous DNA. However, safety and scalability issues hinder viral delivery, while poor efficiency hinders nonviral gene delivery, particularly to hMSCs. Here, we present the use of a pharmacologic agent (glucocorticoid) to overcome barriers to hMSC DNA transfer to enhance transfection using three common nonviral vectors...
February 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/26303405/resveratrol-compounds-inhibit-human-holocarboxylase-synthetase-and-cause-a-lean-phenotype-in-drosophila-melanogaster
#7
Elizabeth L Cordonier, Riem Adjam, Daniel Camara Teixeira, Simone Onur, Richard Zbasnik, Paul E Read, Frank Döring, Vicki L Schlegel, Janos Zempleni
Holocarboxylase synthetase (HLCS) is the sole protein-biotin ligase in the human proteome. HLCS has key regulatory functions in intermediary metabolism, including fatty acid metabolism, and in gene repression through epigenetic mechanisms. The objective of this study was to identify food-borne inhibitors of HLCS that alter HLCS-dependent pathways in metabolism and gene regulation. When libraries of extracts from natural products and chemically pure compounds were screened for HLCS inhibitor activity, resveratrol compounds in grape materials caused an HLCS inhibition of >98% in vitro...
November 2015: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/26269243/the-intestinal-transport-of-bovine-milk-exosomes-is-mediated-by-endocytosis-in-human-colon-carcinoma-caco-2-cells-and-rat-small-intestinal-iec-6-cells
#8
Tovah Wolf, Scott R Baier, Janos Zempleni
BACKGROUND: MicroRNAs play essential roles in gene regulation. A substantial fraction of microRNAs in tissues and body fluids is encapsulated in exosomes, thereby conferring protection against degradation and a pathway for intestinal transport. MicroRNAs in cow milk are bioavailable in humans. OBJECTIVE: This research assessed the transport mechanism of bovine milk exosomes, and therefore microRNAs, in human and rodent intestinal cells. METHODS: The intestinal transport of bovine milk exosomes and microRNAs was assessed using fluorophore-labeled bovine milk exosomes in human colon carcinoma Caco-2 cells and rat small intestinal IEC-6 cells...
October 2015: Journal of Nutrition
https://www.readbyqxmd.com/read/26222444/gene-regulation-by-dietary-micrornas
#9
REVIEW
Janos Zempleni, Scott R Baier, Katherine M Howard, Juan Cui
MicroRNAs (miRNAs) silence genes through destabilizing mRNA or preventing translation of mRNA, thereby playing an essential role in gene silencing. Traditionally, miRNAs have been considered endogenous regulators of genes, i.e., miRNAs synthesized by an organism regulate the genes in that organism. Recently, that dogma has been challenged in studies suggesting that food-borne miRNAs are bioavailable and affect gene expression in mice and humans. While the evidence in support of this theory may be considered weak for miRNAs that originate in plants, there is compelling evidence to suggest that humans use bovine miRNAs in cow's milk and avian miRNAs in chicken eggs for gene regulation...
December 2015: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/26030752/dietary-microrna-database-dmd-an-archive-database-and-analytic-tool-for-food-borne-micrornas
#10
Kevin Chiang, Jiang Shu, Janos Zempleni, Juan Cui
With the advent of high throughput technology, a huge amount of microRNA information has been added to the growing body of knowledge for non-coding RNAs. Here we present the Dietary MicroRNA Databases (DMD), the first repository for archiving and analyzing the published and novel microRNAs discovered in dietary resources. Currently there are fifteen types of dietary species, such as apple, grape, cow milk, and cow fat, included in the database originating from 9 plant and 5 animal species. Annotation for each entry, a mature microRNA indexed as DM0000*, covers information of the mature sequences, genome locations, hairpin structures of parental pre-microRNAs, cross-species sequence comparison, disease relevance, and the experimentally validated gene targets...
2015: PloS One
https://www.readbyqxmd.com/read/25565082/loss-of-mirnas-during-processing-and-storage-of-cow-s-bos-taurus-milk
#11
Katherine M Howard, Rio Jati Kusuma, Scott R Baier, Taylor Friemel, Laura Markham, Jairam Vanamala, Janos Zempleni
MicroRNAs (miRs, miRNAs) play central roles in gene regulation. Previously, we reported that miRNAs from pasteurized, store-bought bovine milk have biological activity in humans. Here, we assessed the effects of milk processing, storage, somatic cell content, and handling by consumers on the degradation of miRNAs in milk; we also quantified miRNAs in dairy products. Pasteurization and homogenization caused a 63% loss of miR-200c, whereas a 67% loss observed for miR-29b was statistically significant only in skim milk...
January 21, 2015: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/25466176/%C3%AE-keto-and-%C3%AE-hydroxyphosphonate-analogs-of-biotin-5-amp-are-inhibitors-of-holocarboxylase-synthetase
#12
Wantanee Sittiwong, Elizabeth L Cordonier, Janos Zempleni, Patrick H Dussault
Holocarboxylase synthetase (HLCS) catalyzes the covalent attachment of biotin to cytoplasmic and mitochondrial carboxylases, nuclear histones, and over a hundred human proteins. Nonhydrolyzable ketophosphonate (β-ketoP) and hydroxyphosphonate (β-hydroxyP) analogs of biotin-5'-AMP inhibit holocarboxylase synthetase (HLCS) with IC50 values of 39.7 μM and 203.7 μM. By comparison, an IC50 value of 7 μM was observed with the previously reported biotinol-5'-AMP. The Ki values, 3.4 μM and 17.3 μM, respectively, are consistent with the IC50 results, and close to the Ki obtained for biotinol-5'-AMP (7 μM)...
December 15, 2014: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/25122645/micrornas-are-absorbed-in-biologically-meaningful-amounts-from-nutritionally-relevant-doses-of-cow-milk-and-affect-gene-expression-in-peripheral-blood-mononuclear-cells-hek-293-kidney-cell-cultures-and-mouse-livers
#13
RANDOMIZED CONTROLLED TRIAL
Scott R Baier, Christopher Nguyen, Fang Xie, Jennifer R Wood, Janos Zempleni
BACKGROUND: MicroRNAs (miRNAs) regulate genes in animals and plants and can be synthesized endogenously. In milk, miRNAs are encapsulated in exosomes, thereby conferring protection against degradation and facilitating uptake by endocytosis. The majority of bovine miRNAs have nucleotide sequences complementary to human gene transcripts, suggesting that miRNAs in milk might regulate human genes. OBJECTIVES: We tested the hypotheses that humans absorb biologically meaningful amounts of miRNAs from nutritionally relevant doses of milk, milk-borne miRNAs regulate human gene expression, and mammals cannot compensate for dietary miRNA depletion by endogenous miRNA synthesis...
October 2014: Journal of Nutrition
https://www.readbyqxmd.com/read/25103574/low-activity-of-lsd1-elicits-a-pro-inflammatory-gene-expression-profile-in-riboflavin-deficient-human-t-lymphoma-jurkat-cells
#14
Dandan Liu, Janos Zempleni
Mono- and dimethylation of lysine (K)-4 in histone H3 (H3K4me1, H3K4me2) create epigenetic gene activation marks that are enriched near the transcription start site of genes. Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD)-dependent demethylase that catalyzes the demethylation of H3K4me1 and H3K4me2, thereby mediating gene repression. This study tested the hypothesis that LSD1 activity depends on the concentrations of the FAD precursor, riboflavin, in cell culture media, and that riboflavin deficiency causes derepression of pro-inflammatory cytokines...
September 2014: Genes & Nutrition
https://www.readbyqxmd.com/read/25022987/nuclear-receptors-and-epigenetic-regulation-opportunities-for-nutritional-targeting-and-disease-prevention
#15
REVIEW
Donato F Romagnolo, Janos Zempleni, Ornella I Selmin
Posttranslational modifications of histones, alterations in the recruitment and functions of non-histone proteins, DNA methylation, and changes in expression of noncoding RNAs contribute to current models of epigenetic regulation. Nuclear receptors (NRs) are a group of transcription factors that, through ligand-binding, act as sensors to changes in nutritional, environmental, developmental, pathophysiologic, and endocrine conditions and drive adaptive responses via gene regulation. One mechanism through which NRs direct gene expression is the assembly of transcription complexes with cofactors and coregulators that possess chromatin-modifying properties...
July 2014: Advances in Nutrition
https://www.readbyqxmd.com/read/24840043/holocarboxylase-synthetase-interacts-physically-with-nuclear-receptor-co-repressor-histone-deacetylase-1-and-a-novel-splicing-variant-of-histone-deacetylase-1-to-repress-repeats
#16
Dandan Liu, Janos Zempleni
HLCS (holocarboxylase synthetase) is a nuclear protein that catalyses the binding of biotin to distinct lysine residues in chromatin proteins. HLCS-dependent epigenetic marks are over-represented in repressed genomic loci, particularly in repeats. Evidence is mounting that HLCS is a member of a multi-protein gene repression complex, which determines its localization in chromatin. In the present study we tested the hypothesis that HLCS interacts physically with N-CoR (nuclear receptor co-repressor) and HDAC1 (histone deacetylase 1), thereby contributing toward the removal of H3K9ac (Lys⁹-acetylated histone H3) gene activation marks and the repression of repeats...
August 1, 2014: Biochemical Journal
https://www.readbyqxmd.com/read/24746830/off-target-effects-of-sulforaphane-include-the-derepression-of-long-terminal-repeats-through-histone-acetylation-events
#17
COMPARATIVE STUDY
Scott R Baier, Richard Zbasnik, Vicki Schlegel, Janos Zempleni
Sulforaphane is a naturally occurring isothiocyanate in cruciferous vegetables. Sulforaphane inhibits histone deacetylases, leading to the transcriptional activation of genes including tumor suppressor genes. The compound has attracted considerable attention in the chemoprevention of prostate cancer. Here we tested the hypothesis that sulforaphane is not specific for tumor suppressor genes but also activates loci such as long terminal repeats (LTRs), which might impair genome stability. Studies were conducted using chemically pure sulforaphane in primary human IMR-90 fibroblasts and in broccoli sprout feeding studies in healthy adults...
June 2014: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/24744315/transcriptional-regulation-of-the-albumin-gene-depends-on-the-removal-of-histone-methylation-marks-by-the-fad-dependent-monoamine-oxidase-lysine-specific-demethylase-1-in-hepg2-human-hepatocarcinoma-cells
#18
COMPARATIVE STUDY
Dandan Liu, Janos Zempleni
Lysine-specific demethylase (LSD) 1 is an FAD-dependent demethylase that catalyzes the removal of methyl groups from lysine-4 in histone H3, thereby mediating gene repression. Here we tested the hypothesis that riboflavin deficiency causes a loss of LSD1 activity in HepG2 human hepatocarcinoma cells, leading to an accumulation of lysine-4-dimethylated histone H3 (H3K4me2) marks in the albumin promoter and aberrant upregulation of albumin expression. Cells were cultured in riboflavin-defined media providing riboflavin at concentrations representing moderately deficient (3...
July 2014: Journal of Nutrition
https://www.readbyqxmd.com/read/24684412/novel-roles-of-holocarboxylase-synthetase-in-gene-regulation-and-intermediary-metabolism
#19
REVIEW
Janos Zempleni, Dandan Liu, Daniel Teixeira Camara, Elizabeth L Cordonier
The role of holocarboxylase synthetase (HLCS) in catalyzing the covalent binding of biotin to the five biotin-dependent carboxylases in humans is well established, as are the essential roles of these carboxylases in the metabolism of fatty acids, the catabolism of leucine, and gluconeogenesis. This review examines recent discoveries regarding the roles of HLCS in assembling a multiprotein gene repression complex in chromatin. In addition, emerging evidence suggests that the number of biotinylated proteins is far larger than previously assumed and includes members of the heat-shock superfamily of proteins and proteins coded by the ENO1 gene...
June 2014: Nutrition Reviews
https://www.readbyqxmd.com/read/24582286/lysine-biotinylation-and-methionine-oxidation-in-the-heat-shock-protein-hsp60-synergize-in-the-elimination-of-reactive-oxygen-species-in-human-cell-cultures
#20
Yong Li, Sridhar A Malkaram, Jie Zhou, Janos Zempleni
Previous studies suggest that the number of proteins containing covalently bound biotin is larger than previously thought. Here, we report the identity of some of these proteins. Using mass spectrometry, we discovered 108 novel biotinylation sites in the human embryonic kidney HEK293 cell proteome; members of the heat shock protein (HSP) superfamily were overrepresented among the novel biotinylated proteins. About half of the biotinylated proteins also displayed various degrees of methionine oxidation, which is known to play an important role in the defense against reactive oxygen species; for biotinylated HSPs, the percent of methionine sulfoxidation approached 100%...
April 2014: Journal of Nutritional Biochemistry
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