keyword
https://read.qxmd.com/read/35018810/fibroblast-growth-factor-21-improves-insulin-action-in-non-lactating-ewes
#21
JOURNAL ARTICLE
Cassandra L Lamb, Sarah L Giesy, Molly M McGuckin, James W Perfield, Anthony Butterfield, Mohammed Moniruzzaman, Norman J Haughey, Joseph W McFadden, Yves R Boisclair
During metabolically demanding physiological states, ruminants and other mammals coordinate nutrient use among tissues by varying the set point of insulin action. This set point is regulated in part by metabolic hormones with some antagonizing (e.g., growth hormone and TNFa) and others potentiating (e.g., adiponectin) insulin action. Fibroblast growth factor-21 (FGF21) was recently identified as a sensitizing hormone in rodent and primate models of defective insulin action. FGF21 administration, however, failed to improve insulin action in dairy cows during the naturally occurring insulin resistance of lactation, raising the possibility that ruminants as a class of animals or lactation as a physiological state are unresponsive to FGF21...
January 12, 2022: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://read.qxmd.com/read/34678224/inhibition-of-neutral-sphingomyelinase-2-reduces-extracellular-vesicle-release-from-neurons-oligodendrocytes-and-activated-microglial-cells-following-acute-brain-injury
#22
JOURNAL ARTICLE
Carolyn Tallon, Silvia Picciolini, Seung-Wan Yoo, Ajit G Thomas, Arindom Pal, Jesse Alt, Cristiano Carlomagno, Alice Gualerzi, Rana Rais, Norman J Haughey, Marzia Bedoni, Barbara S Slusher
Extracellular Vesicles (EVs) are implicated in the spread of pathogenic proteinsin a growing number of neurological diseases. Given this, there is rising interest in developing inhibitors of Neutral Sphingomyelinase 2 (nSMase2), an enzyme critical in EV biogenesis. Our group recently discovered phenyl(R)-(1-(3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl)pyrrolidin-3-yl)carbamate (PDDC), the first potent, selective, orally-available, and brain-penetrable nSMase2 inhibitor, capable of dose-dependently reducing EVs release in vitro and in vivo...
December 2021: Biochemical Pharmacology
https://read.qxmd.com/read/34324668/effects-of-serine-palmitoyltransferase-inhibition-by-myriocin-in-ad-libitum-fed-and-nutrient-restricted-ewes
#23
JOURNAL ARTICLE
Amanda N Davis, William A Myers, Jorge Eduardo Rico, Lin Feng Wang, Crystal Chang, Andrew T Richards, Mohammed Moniruzzaman, Norman J Haughey, Joseph W McFadden
The fungal isolate myriocin inhibits serine palmitoyltransferase and de novo ceramide synthesis in rodents; however, the effects of myriocin on ceramide concentrations and metabolism have not been previously investigated in ruminants. In our study, 12 non-lactating crossbred ewes received an intravenous bolus of myriocin (0, 0.1, 0.3, or 1.0 mg/kg/body weight [BW]; CON, LOW, MOD, or HIGH) every 48 h for 17 d. Ewes consumed a high-energy diet from day 1 to 14 and were nutrient-restricted (straw only) from day 15 to 17...
August 1, 2021: Journal of Animal Science
https://read.qxmd.com/read/33946522/characterization-of-the-plasma-lipidome-in-dairy-cattle-transitioning-from-gestation-to-lactation-identifying-novel-biomarkers-of-metabolic-impairment
#24
JOURNAL ARTICLE
Jorge Eduardo Rico, Sina Saed Samii, Yu Zang, Pragney Deme, Norman J Haughey, Ester Grilli, Joseph W McFadden
The discovery of novel biomarkers for peripartal diseases in dairy cows can improve our understanding of normal and dysfunctional metabolism, and lead to nutritional interventions that improve health and milk production. Our objectives were to characterize the plasma lipidome and identify metabolites associated with common markers of metabolic disease in peripartal dairy cattle. Multiparous Holstein cows ( n = 27) were enrolled 30 d prior to expected parturition. Blood and liver samples were routinely collected through to d 14 postpartum...
April 30, 2021: Metabolites
https://read.qxmd.com/read/33850608/characterization-of-extracellular-vesicles-and-synthetic-nanoparticles-with-four-orthogonal-single-particle-analysis-platforms
#25
JOURNAL ARTICLE
Tanina Arab, Emily R Mallick, Yiyao Huang, Liang Dong, Zhaohao Liao, Zezhou Zhao, Olesia Gololobova, Barbara Smith, Norman J Haughey, Kenneth J Pienta, Barbara S Slusher, Patrick M Tarwater, Juan Pablo Tosar, Angela M Zivkovic, Wyatt N Vreeland, Michael E Paulaitis, Kenneth W Witwer
We compared four orthogonal technologies for sizing, counting, and phenotyping of extracellular vesicles (EVs) and synthetic particles. The platforms were: single-particle interferometric reflectance imaging sensing (SP-IRIS) with fluorescence, nanoparticle tracking analysis (NTA) with fluorescence, microfluidic resistive pulse sensing (MRPS), and nanoflow cytometry measurement (NFCM). EVs from the human T lymphocyte line H9 (high CD81, low CD63) and the promonocytic line U937 (low CD81, high CD63) were separated from culture conditioned medium (CCM) by differential ultracentrifugation (dUC) or a combination of ultrafiltration (UF) and size exclusion chromatography (SEC) and characterized by transmission electron microscopy (TEM) and Western blot (WB)...
April 2021: Journal of Extracellular Vesicles
https://read.qxmd.com/read/33828107/author-correction-palmitate-and-pyruvate-carbon-flux-in-response-to-choline-and-methionine-in-bovine-neonatal-hepatocytes
#26
T L Chandler, S J Erb, William A Myers, Pragney Deme, Norman J Haughey, J W McFadden, H M White
No abstract text is available yet for this article.
April 7, 2021: Scientific Reports
https://read.qxmd.com/read/33798648/nipping-disease-in-the-bud-nsmase2-inhibitors-as-therapeutics-in-extracellular-vesicle-mediated-diseases
#27
REVIEW
Carolyn Tallon, Kristen R Hollinger, Arindom Pal, Benjamin J Bell, Rana Rais, Takashi Tsukamoto, Kenneth W Witwer, Norman J Haughey, Barbara S Slusher
Extracellular vesicles (EVs) are indispensable mediators of intercellular communication, but they can also assume a nefarious role by ferrying pathological cargo that contributes to neurological, oncological, inflammatory, and infectious diseases. The canonical pathway for generating EVs involves the endosomal sorting complexes required for transport (ESCRT) machinery, but an alternative pathway is induced by the enrichment of lipid membrane ceramides generated by neutral sphingomyelinase 2 (nSMase2). Inhibition of nSMase2 has become an attractive therapeutic strategy for inhibiting EV biogenesis, and a growing number of small-molecule nSMase2 inhibitors have shown promising therapeutic activity in preclinical disease models...
July 2021: Drug Discovery Today
https://read.qxmd.com/read/33679577/patterns-and-predictors-of-cognitive-function-among-virally-suppressed-women-with-hiv
#28
JOURNAL ARTICLE
Raha M Dastgheyb, Alison S Buchholz, Kathryn C Fitzgerald, Yanxun Xu, Dionna W Williams, Gayle Springer, Kathryn Anastos, Deborah R Gustafson, Amanda B Spence, Adaora A Adimora, Drenna Waldrop, David E Vance, Joel Milam, Hector Bolivar, Kathleen M Weber, Norman J Haughey, Pauline M Maki, Leah H Rubin
Cognitive impairment remains frequent and heterogeneous in presentation and severity among virally suppressed (VS) women with HIV (WWH). We identified cognitive profiles among 929 VS-WWH and 717 HIV-uninfected women from 11 Women's Interagency HIV Study sites at their first neuropsychological (NP) test battery completion comprised of: Hopkins Verbal Learning Test-Revised, Trail Making, Symbol Digit Modalities, Grooved Pegboard, Stroop, Letter/Animal Fluency, and Letter-Number Sequencing. Using 17 NP performance metrics (T-scores), we used Kohonen self-organizing maps to identify patterns of high-dimensional data by mapping participants to similar nodes based on T-scores and clustering those nodes...
2021: Frontiers in Neurology
https://read.qxmd.com/read/33408815/astrocytes-deliver-ck1-to-neurons-via-extracellular-vesicles-in-response-to-inflammation-promoting-the-translation-and-amyloidogenic-processing-of-app
#29
JOURNAL ARTICLE
Zhigang Li, Mohammed Moniruzzaman, Raha M Dastgheyb, Seung-Wan Yoo, Meina Wang, Hongbo Hao, Jia Liu, Patrizia Casaccia, Carlos Nogueras-Ortiz, Dimitrios Kapogiannis, Barbara S Slusher, Norman J Haughey
Chronic inflammation is thought to contribute to the early pathogenesis of Alzheimer's disease (AD). However, the precise mechanism by which inflammatory cytokines promote the formation and deposition of Aβ remains unclear. Available data suggest that applications of inflammatory cytokines onto isolated neurons do not promote the formation of Aβ, suggesting an indirect mechanism of action. Based on evidence astrocyte derived extracellular vesicles (astrocyte derived EVs) regulate neuronal functions, and data that inflammatory cytokines can modify the molecular cargo of astrocyte derived EVs, we sought to determine if IL-1β promotes the formation of Aβ indirectly through actions of astrocyte derived EVs on neurons...
December 2020: Journal of Extracellular Vesicles
https://read.qxmd.com/read/33307993/serum-ceramide-levels-are-altered-in-multiple-sclerosis
#30
JOURNAL ARTICLE
Angeliki G Filippatou, Mohammed Moniruzzaman, Elias S Sotirchos, Kathryn C Fitzgerald, Grigorios Kalaitzidis, Jeffrey Lambe, Eleni Vasileiou, Shiv Saidha, Jerry L Prince, Norman Haughey, Peter A Calabresi, Pavan Bhargava
BACKGROUND: Sphingolipids are myelin components and inflammatory signaling intermediates. Sphingolipid metabolism may be altered in people with multiple sclerosis (PwMS), but existing studies are limited by small sample sizes. OBJECTIVES: To compare the levels of serum ceramides between PwMS and healthy controls (HCs) and to determine whether ceramide levels correlate with disability status, as well as optical coherence tomography (OCT)-derived rates of retinal layer atrophy...
December 14, 2020: Multiple Sclerosis: Clinical and Laboratory Research
https://read.qxmd.com/read/33279889/white-matter-injury-is-associated-with-reduced-manual-dexterity-and-elevated-serum-ceramides-in-subjects-with-cerebral-small-vessel-disease
#31
JOURNAL ARTICLE
Yousef Hannawi, Lisa R Yanek, Brian G Kral, Lewis C Becker, Dhananjay Vaidya, Norman J Haughey, Diane M Becker, Paul A Nyquist
INTRODUCTION: We have demonstrated that asymptomatic cerebral small vessel disease (cSVD) measured by white matter hyperintensity volume is associated with reduced manipulative manual dexterity on the Grooved Peg Board Test (GPBT) in middle-aged healthy individuals with a family history of early coronary artery disease. In this current study, we aim to identify the association of subcortical white matter microstructural impairment measured by diffusion tensor imaging, manual dexterity measured by GPBT and circulating serums ceramide, another marker for white matter injury...
December 4, 2020: Cerebrovascular Diseases
https://read.qxmd.com/read/33008902/inhibition-of-neutral-sphingomyelinase-2-promotes-remyelination
#32
JOURNAL ARTICLE
Seung-Wan Yoo, Amit Agarwal, Matthew D Smith, Saja S Khuder, Emily G Baxi, Ajit G Thomas, Camilo Rojas, Mohammed Moniruzzaman, Barbara S Slusher, Dwight E Bergles, Peter A Calabresi, Norman J Haughey
Myelination requires a highly organized synthesis of multiple lipid species that regulate myelin curvature and compaction. For reasons that are not understood, central nervous system remyelinated axons often have thin myelin sheaths with a disorganized structure susceptible to secondary demyelination. We found that expression of the sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) during the differentiation of oligodendrocyte progenitor cells (OPCs) to myelinating oligodendrocytes changes their response to inflammatory cytokines...
October 2020: Science Advances
https://read.qxmd.com/read/32944174/influence-of-species-and-processing-parameters-on-recovery-and-content-of-brain-tissue-derived-extracellular-vesicles
#33
JOURNAL ARTICLE
Yiyao Huang, Lesley Cheng, Andrey Turchinovich, Vasiliki Mahairaki, Juan C Troncoso, Olga Pletniková, Norman J Haughey, Laura J Vella, Andrew F Hill, Lei Zheng, Kenneth W Witwer
Extracellular vesicles (EVs) are involved in a wide range of physiological and pathological processes by shuttling material out of and between cells. Tissue EVs may thus lend insights into disease mechanisms and also betray disease when released into easily accessed biological fluids. Since brain-derived EVs (bdEVs) and their cargo may serve as biomarkers of neurodegenerative diseases, we evaluated modifications to a published, rigorous protocol for separation of EVs from brain tissue and studied effects of processing variables on quantitative and qualitative outcomes...
June 30, 2020: Journal of Extracellular Vesicles
https://read.qxmd.com/read/32212091/associations-between-antiretrovirals-and-cognitive-function-in-women-with-hiv
#34
JOURNAL ARTICLE
Leah H Rubin, Yuliang Li, Kathryn C Fitzgerald, Raha Dastgheyb, Amanda B Spence, Pauline M Maki, Anjali Sharma, Deborah R Gustafson, Joel Milam, Kathleen M Weber, Adaora A Adimora, Norman J Haughey, Igho Ofotokun, Margaret A Fischl, Deborah Konkle-Parker, Yanxun Xu, Dionna W Williams
Cognitive complications persist in antiretroviral therapy(ART)-treated people with HIV. However, the pattern and severity of domain-specific cognitive performance is variable and may be exacerbated by ART-mediated neurotoxicity. 929 women with HIV(WWH) from the Women's Interagency HIV Study who were classified into subgroups based on sociodemographic and longitudinal behavioral and clinical data using semi-parametric latent class trajectory modelling. Five subgroups were comprised of: 1) well-controlled HIV with vascular comorbidities(n = 116); 2) profound HIV legacy effects(CD4 nadir <250 cells/μL; n = 275); 3) primarily <45 year olds with hepatitis C(n = 165); 4) primarily 35-55 year olds(n = 244), and 5) poorly-controlled HIV/substance use(n = 129)...
March 24, 2020: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://read.qxmd.com/read/31930991/bioenergetic-adaptations-to-hiv-infection-could-modulation-of-energy-substrate-utilization-improve-brain-health-in-people-living-with-hiv-1
#35
REVIEW
Pragney Deme, Camilo Rojas, Barbara S Slusher, Zahra Afghah, Jonathan D Geiger, Norman J Haughey
The human brain consumes more energy than any other organ in the body and it relies on an uninterrupted supply of energy in the form of adenosine triphosphate (ATP) to maintain normal cognitive function. This constant supply of energy is made available through an interdependent system of metabolic pathways in neurons, glia and endothelial cells that each have specialized roles in the delivery and metabolism of multiple energetic substrates. Perturbations in brain energy metabolism is associated with a number of different neurodegenerative conditions including impairments in cognition associated with infection by the Human Immunodeficiency Type 1 Virus (HIV-1)...
January 10, 2020: Experimental Neurology
https://read.qxmd.com/read/31863022/lipid-accumulation-and-oxidation-in-glioblastoma-multiforme
#36
JOURNAL ARTICLE
Bouchra Taïb, Amine M Aboussalah, Mohammed Moniruzzaman, Suming Chen, Norman J Haughey, Sangwon F Kim, Rexford S Ahima
Glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite the multimodal standard treatments for GBM, the median survival is still about one year. Analysis of brain tissues from GBM patients shows that lipid droplets are highly enriched in tumor tissues while undetectable in normal brain tissues, yet the identity and functions of lipid species in GBM are not well understood. The aims of the present work are to determine how GBM utilizes fatty acids, and assess their roles in GBM proliferation...
December 20, 2019: Scientific Reports
https://read.qxmd.com/read/31669360/proteome-characterization-of-small-extracellular-vesicles-from-spared-nerve-injury-model-of-neuropathic-pain
#37
JOURNAL ARTICLE
Renee Jean-Toussaint, Yuzhen Tian, Amrita Datta Chaudhuri, Norman J Haughey, Ahmet Sacan, Seena K Ajit
Exosomes are 30-150 nm extracellular vesicles mediating intercellular communication. Disease states can alter exosome composition affecting the message carried and thereby, its functional impact. The objective of this study was to identify proteins present in these vesicles in a mouse model of neuropathic pain induced by spared nerve injury (SNI). Small extracellular vesicles (sEVs) were purified from serum four weeks after SNI surgery and the protein composition was determined using tandem mass spectrometry and cytokine array...
January 16, 2020: Journal of Proteomics
https://read.qxmd.com/read/31632506/lipidomic-characterization-of-extracellular-vesicles-in-human-serum
#38
JOURNAL ARTICLE
Suming Chen, Amrita Datta-Chaudhuri, Pragney Deme, Alex Dickens, Raha Dastgheyb, Pavan Bhargava, Honghao Bi, Norman J Haughey
There is a wide variety of extracellular vesicles (EVs) that differ in size and cargo composition. EVs isolated from human plasma or serum carry lipid, protein, and RNA cargo that provides insights to the regulation of normal physiological processes, and to pathological states. Specific populations of EVs have been proposed to contain protein and RNA cargo that are biomarkers for neurologic and systemic diseases. Although there is a considerable amount of evidence that circulating lipids are biomarkers for multiple disease states, it not clear if these lipid biomarkers are enriched in EVs, or if specific populations of EVs are enriched for particular classes of lipid...
January 2019: Journal of Circulating Biomarkers
https://read.qxmd.com/read/31631575/role-of-human-induced-pluripotent-stem-cell-derived-spinal-cord-astrocytes-in-the-functional-maturation-of-motor-neurons-in-a-multielectrode-array-system
#39
JOURNAL ARTICLE
Arens Taga, Raha Dastgheyb, Christa Habela, Jessica Joseph, Jean-Philippe Richard, Sarah K Gross, Giuseppe Lauria, Gabsang Lee, Norman Haughey, Nicholas J Maragakis
The ability to generate human-induced pluripotent stem cell (hiPSC)-derived neural cells displaying region-specific phenotypes is of particular interest for modeling central nervous system biology in vitro. We describe a unique method by which spinal cord hiPSC-derived astrocytes (hiPSC-A) are cultured with spinal cord hiPSC-derived motor neurons (hiPSC-MN) in a multielectrode array (MEA) system to record electrophysiological activity over time. We show that hiPSC-A enhance hiPSC-MN electrophysiological maturation in a time-dependent fashion...
October 21, 2019: Stem Cells Translational Medicine
https://read.qxmd.com/read/31469478/stimulus-dependent-modifications-in-astrocyte-derived-extracellular-vesicle-cargo-regulate-neuronal-excitability
#40
JOURNAL ARTICLE
Amrita Datta Chaudhuri, Raha M Dasgheyb, Lauren R DeVine, Honghao Bi, Robert N Cole, Norman J Haughey
Extracellular vesicles have now emerged as key players in cell-to-cell communication. This is particularly important in the central nervous system, where glia-neuron cross-talk helps maintain normal neuronal function. Astrocyte-derived extracellular vesicles (ADEVs) secreted constitutively promote neurite outgrowth and neuronal survival. However, extracellular stimuli can alter the cargo and downstream functions of ADEVs. For example, ADEVs secreted in response to inflammation contain cargo microRNAs and proteins that reduce neurite outgrowth, neuronal firing, and promote neuronal apoptosis...
August 30, 2019: Glia
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