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https://www.readbyqxmd.com/read/29131145/metabolomics-based-discovery-of-a-metabolite-that-enhances-oligodendrocyte-maturation
#1
Brittney A Beyer, Mingliang Fang, Benjamin Sadrian, J Rafael Montenegro-Burke, Warren C Plaisted, Bernard P C Kok, Enrique Saez, Toru Kondo, Gary Siuzdak, Luke L Lairson
Endogenous metabolites play essential roles in the regulation of cellular identity and activity. Here we have investigated the process of oligodendrocyte precursor cell (OPC) differentiation, a process that becomes limiting during progressive stages of demyelinating diseases, including multiple sclerosis, using mass-spectrometry-based metabolomics. Levels of taurine, an aminosulfonic acid possessing pleotropic biological activities and broad tissue distribution properties, were found to be significantly elevated (∼20-fold) during the course of oligodendrocyte differentiation and maturation...
November 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29129786/mechanisms-by-which-a-very-low-calorie-diet-reverses-hyperglycemia-in-a-rat-model-of-type-2-diabetes
#2
Rachel J Perry, Liang Peng, Gary W Cline, Yongliang Wang, Aviva Rabin-Court, Joongyu D Song, Dongyan Zhang, Xian-Man Zhang, Yuichi Nozaki, Sylvie Dufour, Kitt Falk Petersen, Gerald I Shulman
Caloric restriction rapidly reverses type 2 diabetes (T2D), but the mechanism(s) of this reversal are poorly understood. Here we show that 3 days of a very-low-calorie diet (VLCD, one-quarter their typical intake) lowered plasma glucose and insulin concentrations in a rat model of T2D without altering body weight. The lower plasma glucose was associated with a 30% reduction in hepatic glucose production resulting from suppression of both gluconeogenesis from pyruvate carboxylase (VPC), explained by a reduction in hepatic acetyl-CoA content, and net hepatic glycogenolysis...
November 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29121917/a-single-rapamycin-dose-protects-against-late-stage-experimental-cerebral-malaria-via-modulation-of-host-immunity-endothelial-activation-and-parasite-sequestration
#3
Pedro Mejia, J Humberto Treviño-Villarreal, Justin S Reynolds, Mariana De Niz, Andrew Thompson, Matthias Marti, James R Mitchell
BACKGROUND: Maladaptive immune responses during cerebral malaria (CM) result in high mortality despite opportune anti-malarial chemotherapy. Rapamycin, an FDA-approved immunomodulator, protects against experimental cerebral malaria (ECM) in mice through effects on the host. However, the potential for reduced adaptive immunity with chronic use, combined with an incomplete understanding of mechanisms underlying protection, limit translational potential as an adjunctive therapy in CM. RESULTS: The results presented herein demonstrate that a single dose of rapamycin, provided as late as day 4 or 5 post-infection, protected mice from ECM neuropathology and death through modulation of distinct host responses to infection...
November 9, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29110360/enhancing-engineered-vascular-networks-in-vitro-and-in-vivo-the-effects-of-igf1-on-vascular-development-and-durability
#4
Claudia C Friedrich, Yunfeng Lin, Alexander Krannich, Yinan Wu, Joseph P Vacanti, Craig M Neville
OBJECTIVES: Creation of functional, durable vasculature remains an important goal within the field of regenerative medicine. Engineered biological vasculature has the potential to restore or improve human tissue function. We hypothesized that the pleotropic effects of insulin-like growth factor 1 (IGF1) would enhance the engineering of capillary-like vasculature. MATERIALS AND METHODS: The impact of IGF1 upon vasculogenesis was examined in in vitro cultures for a period of up to 40 days and as subcutaneous implants within immunodeficient mice...
November 7, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/29104539/annonaceae-breaking-the-wall-of-inflammation
#5
REVIEW
Ali Attiq, Juriyati Jalil, Khairana Husain
Inventories of tropical forests have listed Annonaceae as one of the most diverse plant families. For centuries, it is employed in traditional medicines to cure various pathological conditions including snakebite, analgesic, astringent, diarrhea, dysentery, arthritis pain, rheumatism, neuralgia, and weight loss etc. Phytochemical analysis of Annonaceae family have reported the occurrence of alkaloids, flavonoids, triterpenes, diterpenes and diterpene flavone glycosides, sterols, lignans, and annonaceous acetogenin characteristically affiliated with Annonaceae sp...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29090850/immune-suppressive-effects-of-il-6-on-t-cell-mediated-anti-tumor-immunity
#6
REVIEW
Hirotake Tsukamoto, Koji Fujieda, Satoru Senju, Tokunori Ikeda, Hiroyuki Oshiumi, Yasuharu Nishimura
Accompanied by the growing clinical applications of immunotherapy in treatment for cancer patients, the development of novel therapeutic approaches to reverse the immune-suppressive environment in cancer patients is eagerly anticipated, because the success of cancer immunotherapy is currently limited by immune-suppressive effects in tumor-bearing hosts. Interleukin (IL)-6, a pleotropic pro-inflammatory cytokine, participates in tumor cell-autonomous processes that are required for their survival and growth, and is therefore known as a poor prognostic factor in cancer patients...
November 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/29046483/deficiency-of-shank2-causes-mania-like-behavior-that-responds-to-mood-stabilizers
#7
Andrea L Pappas, Alexandra L Bey, Xiaoming Wang, Mark Rossi, Yong Ho Kim, Haidun Yan, Fiona Porkka, Lara J Duffney, Samantha M Phillips, Xinyu Cao, Jin-Dong Ding, Ramona M Rodriguiz, Henry H Yin, Richard J Weinberg, Ru-Rong Ji, William C Wetsel, Yong-Hui Jiang
Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underlying the pleotropic effects of SHANK2 mutations are poorly understood. We generated and characterized a line of Shank2 mutant mice by deleting exon 24 (Δe24). Shank2Δe24-/- mice engage in significantly increased locomotor activity, display abnormal reward-seeking behavior, are anhedonic, have perturbations in circadian rhythms, and show deficits in social and cognitive behaviors...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/28992028/genomics-symposium-using-genomic-approaches-to-uncover-sources-of-variation-in-age-at-puberty-and-reproductive-longevity-in-sows
#8
H R Wijesena, C A Lents, J-J Riethoven, M D Trenhaile-Grannemann, J F Thorson, B N Keel, P S Miller, M L Spangler, S D Kachman, D C Ciobanu
Genetic variants associated with traits such as age at puberty and litter size could provide insight into the underlying genetic sources of variation impacting sow reproductive longevity and productivity. Genomewide characterization and gene expression profiling were used using gilts from the University of Nebraska-Lincoln swine resource population ( = 1,644) to identify genetic variants associated with age at puberty and litter size traits. From all reproductive traits studied, the largest fraction of phenotypic variation explained by the Porcine SNP60 BeadArray was for age at puberty (27...
September 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28979043/heparin-effects-upon-the-glycocalyx-and-endothelial-cells
#9
REVIEW
Bruce D Spiess
Unfractionated heparin (UFH) is the most widely used injectable medication in the United States. UFH is a poly-dispersed, relatively impure combination of many polysaccharides known as a glycosaminoglycan. It is used as the primary anticoagulant for heart surgery as well as for active treatment of deep venous thrombosis, vascular thrombosis, stroke, and many other potentially catastrophic clotting syndromes. Many perfusionists and cardiac team members know little of the biology of UFH other than its use for cardiopulmonary bypass...
September 2017: Journal of Extra-corporeal Technology
https://www.readbyqxmd.com/read/28978323/synergistic-oligodeoxynucleotide-strongly-promotes-cpg-induced-interleukin-6-production
#10
Shireen Nigar, Yoshinari Yamamoto, Takuma Okajima, Suguru Shigemori, Takashi Sato, Tasuku Ogita, Takeshi Shimosato
BACKGROUND: Bacterial genomes span a significant portion of diversity, reflecting their adaptation strategies; these strategies include nucleotide usage biases that affect chromosome configuration. Here, we explore an immuno-synergistic oligodeoxynucleotide (iSN-ODN, named iSN34), derived from Lactobacillus rhamnosus GG (LGG) genomic sequences, that exhibits a synergistic effect on immune response to CpG-induced immune activation. METHODS: The sequence of iSN34 was designed based on the genomic sequences of LGG...
October 4, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28967174/the-nitrate-reduction-gene-cluster-components-exert-lineage-dependent-contributions-to-optimization-of-sinorhizobium-symbiosis-with-soybeans
#11
Li Xue Liu, Qin Qin Li, Yun Zeng Zhang, Yue Hu, Jian Jiao, Hui Juan Guo, Xing Xing Zhang, Biliang Zhang, Wen Xin Chen, Chang Fu Tian
Receiving nodulation and nitrogen fixation genes does not guarantee rhizobia an effective symbiosis with legumes. Here, variations in gene content were determined for three Sinorhizobium species showing contrasting symbiotic efficiency on soybeans. A nitrate-reduction gene cluster absent in S. sojae was found to be essential for symbiotic adaptations of S. fredii and S. sp. III. In S. fredii, the deletion mutation of the nap (nitrate reductase), instead of nir (nitrite reductase) and nor (nitric oxide reductase), led to defects in nitrogen-fixation (Fix(-) )...
October 2, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28960806/regional-evidence-and-international-recommendations-to-guide-lipid-management-in-asian-patients-with-type-2-diabetes-with-special-reference-to-renal-dysfunction
#12
REVIEW
Titus Wl Lau, Kevin Ek Tan, Jason Cj Choo, T G Ng, Tavintharan S, Juliana C N Chan
The anticipated increase in the prevalence and incidence of type 2 diabetes in Asia, and its associated cardiovascular-renal complications will place a significant burden on patients, caregivers and society. Despite the proven effectiveness of lipid management in reducing these complications, there are major treatment gaps especially in Asian patients with young-onset diabetes and chronic kidney disease. Recent international guidelines recommended the adoption of absolute risk estimation of atherosclerosis and cardiovascular disease to guide treatment intensity...
September 28, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28959263/deciphering-of-the-human-interferon-regulated-proteome-by-mass-spectrometry-based-quantitative-analysis-reveals-extent-and-dynamics-of-protein-induction-and-repression
#13
Dominik A Megger, Jos Philipp, Vu Thuy Khanh Le-Trilling, Barbara Sitek, Mirko Trilling
Interferons (IFNs) are pleotropic cytokines secreted upon encounter of pathogens and tumors. Applying their antipathogenic, antiproliferative, and immune stimulatory capacities, recombinant IFNs are frequently prescribed as drugs to treat different diseases. IFNs act by changing the gene expression profile of cells. Due to characteristics such as rapid gene induction and signaling, IFNs also represent prototypical model systems for various aspects of biomedical research (e.g., signal transduction). In regard to the signaling and activated promoters, IFNs can be subdivided into two groups...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28944314/ligand-activation-of-the-ah-receptor-contributes-to-gastrointestinal-homeostasis
#14
Iain A Murray, Gary H Perdew
The Ah receptor (AHR) is capable of binding a structurally diverse group of compounds that can be found in the diet, produced by bacteria in the gut and through endogenous metabolism. The gastrointestinal tract is a rich source of AHR ligands, which have been shown to protect the gut upon challenge with either pathogenic bacteria or toxic chemicals. The human AHR can be activated by a broader range of ligands compared to the mouse AHR, suggesting that studies in mice may underestimate the impact of AHR ligands in the human gut...
February 2017: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/28921675/altered-cav1-2-function-in-the-timothy-syndrome-mouse-model-produces-ascending-serotonergic-abnormalities
#15
Daniel G Ehlinger, Kathryn G Commons
Polymorphism in the gene CACNA1C, encoding the pore-forming subunit of Cav1.2 L-type calcium channels, has one of the strongest genetic linkages to schizophrenia, bipolar disorder and major depressive disorder: psychopathologies in which serotonin signaling has been implicated. Additionally, a gain-of-function mutation in CACNA1C is responsible for the neurodevelopmental disorder Timothy syndrome that presents with prominent behavioral features on the autism spectrum. Given an emerging role for serotonin in the etiology of autism spectrum disorders (ASD), we investigate the relationship between Cav1...
October 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28913617/fingolimod-induces-neuronal-specific-gene-expression-with-potential-neuroprotective-outcomes-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#16
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
Fingolimod (FTY720), a structural analogue of sphingosine, targets sphingosine-1-phosphate receptor signaling and is currently an immunomodulatory therapy for multiple sclerosis. Fingolimod accesses the central nervous system (CNS) where its active metabolite, fingolimod phosphate (FTY720-P), has pleotropic neuroprotective effects in an inflammatory microenvironment. To investigate potential neuronal-specific mechanisms of fingolimod neuroprotection, we cultured the human neuronal progenitor cell line, hNP1, in differentiation medium supplemented with HIV- or Mock-infected supernatants, with or without FTY720-P...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28911530/autophagy-inducing-effect-of-pterostilbene-a%C3%A2-prospective-therapeutic-preventive-option-for-skin-diseases
#17
Rong-Jane Chen, Yu-Hsuan Lee, Ya-Ling Yeh, Wun-Syuan Wu, Chi-Tang Ho, Chia-Yi Li, Bour-Jr Wang, Ying-Jan Wang
Pterostilbene is a naturally occurring analog of resveratrol with many health benefits. These health benefits are associated with its antioxidant activity, anti-inflammatory effects, and chemopreventive effects attributed to its unique structure. The skin cancer chemopreventive potential of pterostilbene is supported by a variety of mechanistic studies confirming the anti-inflammatory effects in skin cancer models. Molecular biological studies have identified that pterostilbene targets pleotropic signaling pathways, including those involved in mitogenesis, cell cycle regulation, and apoptosis...
January 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28880939/arf6-mediates-nephrin-tyrosine-phosphorylation-induced-podocyte-cellular-dynamics
#18
Jamie S Lin, Jin Seok Jeon, Qingfeng Fan, Hetty N Wong, Matthew B Palmer, Lawrence B Holzman
ADP-ribosylation factor 6 (ARF6) is a small GTPase necessary for regulating cellular structure, motility, and vesicle trafficking. In several cellular systems, ARF6 was shown to regulate actin dynamics in coordination with Rac1, a Rho small GTPase. We examined the function of ARF6 in the kidney podocyte because Rac1 was implicated in kidney diseases involving this cell. We found that ARF6 expression was enriched in human podocytes and that it modulated podocyte cytoskeletal dynamics through a functional interaction with nephrin, an intercellular junction protein necessary for podocyte injury-induced signaling requiring activation by tyrosine phosphorylation of its cytoplasmic domain...
2017: PloS One
https://www.readbyqxmd.com/read/28869931/a-phase-ii-exploratory-study-of-pxd-101-belinostat-followed-by-zevalin-in-patients-with-relapsed-aggressive-high-risk-lymphoma
#19
Soham D Puvvada, José M Guillén-Rodríguez, Xavier I Rivera, Kara Heard, Lora Inclan, Monika Schmelz, Jonathan H Schatz, Daniel O Persky
OBJECTIVE: Aggressive lymphomas (aNHL) including diffuse large B-cell lymphoma (DLBCL) have poor outcomes in relapsed refractory patients. Prior studies have demonstrated that loss of major histocompatibility complex class II (MHCII) expression in DLBCL is associated with poor survival. The objective of this single-arm phase II study was to evaluate if PXD-101 would increase MHCII expression, synergize with Zevalin, and improve clinical outcomes. METHODS: This was a single-center open-label phase II trial (NCT01686165) geared toward heavily pretreated patients with CD20-positive aNHL...
September 5, 2017: Oncology
https://www.readbyqxmd.com/read/28757913/the-involvement-of-mg-2-in-regulation-of-cellular-and-mitochondrial-functions
#20
REVIEW
Ivana Pilchova, Katarina Klacanova, Zuzana Tatarkova, Peter Kaplan, Peter Racay
Mg(2+) is an essential mineral with pleotropic impacts on cellular physiology and functions. It acts as a cofactor of several important enzymes, as a regulator of ion channels such as voltage-dependent Ca(2+) channels and K(+) channels and on Ca(2+)-binding proteins. In general, Mg(2+) is considered as the main intracellular antagonist of Ca(2+), which is an essential secondary messenger initiating or regulating a great number of cellular functions. This review examines the effects of Mg(2+) on mitochondrial functions with a particular focus on energy metabolism, mitochondrial Ca(2+) handling, and apoptosis...
2017: Oxidative Medicine and Cellular Longevity
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