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https://www.readbyqxmd.com/read/29331565/saroglitazar-reduces-obesity-and-associated-inflammatory-consequences-in-murine-adipose-tissue
#1
Durgesh Kumar, Umesh Kumar Goand, Sanchita Gupta, Kripa Shankar, Salil Varshney, Sujith Rajan, Ankita Srivastava, Abhishek Gupta, Achchhe Lal Vishwakarma, Anurag Kumar Srivastava, Anil N Gaikwad
Prevailing knowledge links chronic low-grade inflammation in the adipose tissue to obesity and its associated metabolic complications. In this study, we evaluated immunometabolic effects of a recently launched dual peroxisome proliferator-activated receptor (PPAR) α & γ agonist 'Saroglitazar' in a mouse model of diet-induced obesity (DIO). Body composition analysis revealed that saroglitazar treatment promoted hepatic weight gain, while attenuated epididymal white adipose tissue (eWAT) mass in DIO. In the eWAT of saroglitazar treated mice, histological analysis showed reduced adipocyte hypertrophy and matrix deposition (picrosirius red staining)...
January 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29330785/genetic-knockdown-and-pharmacologic-inhibition-of-hypoxia-inducible-factor-hif-hydroxylases
#2
Christina Pickel, Cormac T Taylor, Carsten C Scholz
Reduced oxygen supply that does not satisfy tissue and cellular demand (hypoxia) regularly occurs both in health and disease. Hence, the capacity for cellular oxygen sensing is of vital importance for each cell to be able to alter its energy metabolism and promote adaptation to hypoxia. The hypoxia-inducible factor (HIF) prolyl hydroxylases 1-3 (PHD1-3) and the asparagine hydroxylase factor-inhibiting HIF (FIH) are the primary cellular oxygen sensors, which confer cellular oxygen-dependent sensitivity upon HIF as well as other hypoxia-sensitive pathways, such as nuclear factor κB (NF-κB)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330372/non-estrogenic-xanthohumol-derivatives-mitigate-insulin-resistance-and-cognitive-impairment-in-high-fat-diet-induced-obese-mice
#3
Cristobal L Miranda, Lance A Johnson, Oriane de Montgolfier, Valerie D Elias, Lea S Ullrich, Joshua J Hay, Ines L Paraiso, Jaewoo Choi, Ralph L Reed, Johana S Revel, Chrissa Kioussi, Gerd Bobe, Urszula T Iwaniec, Russell T Turner, Benita S Katzenellenbogen, John A Katzenellenbogen, Paul R Blakemore, Adrian F Gombart, Claudia S Maier, Jacob Raber, Jan F Stevens
Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional glucose and lipid metabolism in animal models of metabolic syndrome (MetS). However, its metabolic transformation into the estrogenic metabolite, 8-prenylnaringenin (8-PN), poses a potential health concern for its use in humans. To address this concern, we evaluated two hydrogenated derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for estrogen receptors α and β, and which cannot be metabolically converted into 8-PN...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330301/genetic-control-of-predominantly-error-free-replication-through-an-acrolein-derived-minor-groove-dna-adduct
#4
Jung-Hoon Yoon, Richard P Hodge, Linda C Hackfeld, Jeseong Park, Jayati Roy Choudhury, Satya Prakash, Louise Prakash
Acrolein, an α, β unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from metabolic oxidation of polyamines, and it is an ubiquitous environmental pollutant. The reaction of acrolein with the N2 of guanine in DNA leads to the formation of γ-hydroxy-1-N2-propano-2' deoxyguanosine (γ-HOPdG) which can exist in DNA in a ring-closed or a ring-opened form. Here we identify the translesion synthesis (TLS) DNA polymerases (Pols) which conduct replication through the permanently ring-opened reduced form of γ-HOPdG [(r) γ-HOPdG] and show that replication through this adduct is mediated via Rev1/Polη, Polι/Polκ, and Polθ dependent pathways, respectively...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29328908/metabolic-induction-of-trained-immunity-through-the-mevalonate-pathway
#5
Siroon Bekkering, Rob J W Arts, Boris Novakovic, Ioannis Kourtzelis, Charlotte D C C van der Heijden, Yang Li, Calin D Popa, Rob Ter Horst, Julia van Tuijl, Romana T Netea-Maier, Frank L van de Veerdonk, Triantafyllos Chavakis, Leo A B Joosten, Jos W M van der Meer, Henk Stunnenberg, Niels P Riksen, Mihai G Netea
Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Rather, the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328786/connections-between-metabolism-and-epigenetics-in-programming-cellular-differentiation
#6
Danielle A Chisolm, Amy S Weinmann
Researchers are intensifying efforts to understand the mechanisms by which changes in metabolic states influence differentiation programs. An emerging objective is to define how fluctuations in metabolites influence the epigenetic states that contribute to differentiation programs. This is because metabolites such as S-adenosylmethionine, acetyl-CoA, α-ketoglutarate, 2-hydroxyglutarate, and butyrate are donors, substrates, cofactors, and antagonists for the activities of epigenetic-modifying complexes and for epigenetic modifications...
January 12, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29327320/phylogenetic-analysis-and-biological-evaluation-of-marine-endophytic-fungi-derived-from-red-sea-sponge-hyrtios-erectus
#7
Mervat Morsy Abbas Ahmed El-Gendy, Shaymaa M M Yahya, Ahmed R Hamed, Maha M Soltan, Ahmed Mohamed Ahmed El-Bondkly
Forty-four endophytic fungal isolates obtained from marine sponge, Hyrtios erectus, were evaluated and screened for their hydrolase activities. Most of the isolates were found to be prolific producers of hydrolytic enzymes. Only 11 isolates exhibited maximum cellular contents of lipids, rhamnolipids, and protein in the fungal isolates under the isolation numbers MERVA5, MERVA22, MERVA25, MERVA29, MERVA32, MERVA34, MERV36, MERVA39, MERVA42, MERVA43, and MERVA44. These isolate extracts exhibit the highest reducing activities against carbohydrate-metabolizing enzymes including α-amylase, α-glucosidase, β-glucosidase, β-glucuronidase, and tyrosinase...
January 12, 2018: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29323772/the-role-of-nrf2-signaling-in-counteracting-neurodegenerative-diseases
#8
REVIEW
Albena T Dinkova-Kostova, Rumen V Kostov, Aleksey G Kazantsev
The transcription factor Nrf2 (nuclear factor erythroid 2 p45-related factor 2) functions at the interface of cellular redox and intermediary metabolism. Nrf2 target genes encode antioxidant enzymes, and proteins involved in xenobiotic detoxification, repair and removal of damaged proteins and organelles, inflammation, and mitochondrial bioenergetics. The function of Nrf2 is altered in many neurodegenerative disorders, such as Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis and Friedreich's ataxia...
January 11, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29323662/crispr-cas9-based-genome-wide-screening-of-toxoplasma-gondii
#9
Saima M Sidik, Diego Huet, Sebastian Lourido
Apicomplexan parasites, such as Toxoplasma gondii, cause extensive morbidity and mortality in humans and livestock, highlighting the need for a deeper understanding of their molecular biology. Although techniques for the generation of targeted gene disruptions have long been available for apicomplexans, such methods are not readily scalable to the entire genome. We recently used CRISPR-Cas9 to disrupt all nuclear protein-coding genes in T. gondii using a pooled format. The method relies on transfection of a guide RNA library into parasites constitutively expressing Cas9...
January 2018: Nature Protocols
https://www.readbyqxmd.com/read/29323266/aif-loss-deregulates-hematopoiesis-and-reveals-different-adaptive-metabolic-responses-in-bone-marrow-cells-and-thymocytes
#10
Lauriane Cabon, Audrey Bertaux, Marie-Noëlle Brunelle-Navas, Ivan Nemazanyy, Laurianne Scourzic, Laure Delavallée, Laura Vela, Mathieu Baritaud, Sandrine Bouchet, Cécile Lopez, Vu Quang Van, Kevin Garbin, Danielle Chateau, Françoise Gilard, Marika Sarfati, Thomas Mercher, Olivier A Bernard, Santos A Susin
Mitochondrial metabolism is a tightly regulated process that plays a central role throughout the lifespan of hematopoietic cells. Herein, we analyze the consequences of the mitochondrial oxidative phosphorylation (OXPHOS)/metabolism disorder associated with the cell-specific hematopoietic ablation of apoptosis-inducing factor (AIF). AIF-null (AIF-/Y ) mice developed pancytopenia that was associated with hypocellular bone marrow (BM) and thymus atrophy. Although myeloid cells were relatively spared, the B-cell and erythroid lineages were altered with increased frequencies of precursor B cells, pro-erythroblasts I, and basophilic erythroblasts II...
January 11, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29322794/integrated-analysis-of-the-rna-seq-data-of-liver-hepatocellular-carcinoma
#11
H Xue, L Luo, Y T Yao, L L Wei, S P Deng, X L Huang
The present study aimed to explore the genetic changes involved in the liver hepatocellular carcinoma (HCC) development. The RNA-Seq data of 212 HCC tissue samples and 50 normal tissue samples were downloaded using TCGA-Assembler. A total of 4 subgroups were obtained, and 4167, 6279, 5379, and 2548 DEGs were screened in group 1, group 2, group 3, and group 4, respectively. Enrichment analysis found that cell cycle, metabolism, and translation related terms were the most significantly changed functions and pathways...
2018: Neoplasma
https://www.readbyqxmd.com/read/29321559/the-role-of-parafacial-neurons-in-the-control-of-breathing-during-exercise
#12
Alla Korsak, Shahriar Sheikhbahaei, Asif Machhada, Alexander V Gourine, Robert T R Huckstepp
Neuronal cell groups residing within the retrotrapezoid nucleus (RTN) and C1 area of the rostral ventrolateral medulla oblongata contribute to the maintenance of resting respiratory activity and arterial blood pressure, and play an important role in the development of cardiorespiratory responses to metabolic challenges (such as hypercapnia and hypoxia). In rats, acute silencing of neurons within the parafacial region which includes the RTN and the rostral aspect of the C1 circuit (pFRTN/C1), transduced to express HM4D (Gi-coupled) receptors, was found to dramatically reduce exercise capacity (by 60%), determined by an intensity controlled treadmill running test...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321333/microrna-130a-regulates-both-hcv-and-hbv-replication-through-a-central-metabolic-pathway
#13
Xiaoqiong Duan, Shilin Li, Jacinta A Holmes, Zeng Tu, Yujia Li, Dachuan Cai, Xiao Liu, Wenting Li, Chunhui Yang, Baihai Jiao, Esperance A Schaefer, Dahlene N Fusco, Shadi Salloum, Limin Chen, Wenyu Lin, Raymond T Chung
BACKGROUND: HCV infection has been shown to regulate miR-130a in patient biopsies and in cultured cells. We sought to identify miR-130a target genes and to explore the mechanisms by which miR-130a regulates HCV and HBV replication.METHODS: We used bioinformatics software including miRanda, TargetScan, PITA and RNAhybrid to predict potential miR-130a target genes. miR-130a and its target genes were overexpressed, or knocked down by siRNA or by CRISPR/Cas9 gRNA, respectively. Selected gene mRNAs and their proteins, together with HCV replication in OR6 cells, JFH1 HCV-infected Huh7...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29320709/metabolic-reprogramming-via-targeting-cd38-nadase-augments-adoptive-t-cell-therapy
#14
Mario R Fernandez, John L Cleveland
One strategy to improve the potency of adoptive T cell therapy is to augment the function and persistence of anti-tumor T cells. In this issue of Cell Metabolism, Chatterjee et al. (2018) demonstrate that intratumoral CD4+ T cell functions and memory can be improved by targeting a CD38-NAD+-Sirt1-Foxo1 metabolic circuit.
January 9, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29320490/the-glutamine-synthetase-of-trypanosoma-cruzi-is-required-for-its-resistance-to-ammonium-accumulation-and-evasion-of-the-parasitophorous-vacuole-during-host-cell-infection
#15
Marcell Crispim, Flávia Silva Damasceno, Agustín Hernández, María Julia Barisón, Ismael Pretto Sauter, Raphael Souza Pavani, Alexandre Santos Moura, Elizabeth Mieko Furusho Pral, Mauro Cortez, Maria Carolina Elias, Ariel Mariano Silber
Trypanosoma cruzi, the etiological agent of Chagas disease, consumes glucose and amino acids depending on the environmental availability of each nutrient during its complex life cycle. For example, amino acids are the major energy and carbon sources in the intracellular stages of the T. cruzi parasite, but their consumption produces an accumulation of NH4+ in the environment, which is toxic. These parasites do not have a functional urea cycle to secrete excess nitrogen as low-toxicity waste. Glutamine synthetase (GS) plays a central role in regulating the carbon/nitrogen balance in the metabolism of most living organisms...
January 10, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29319817/high-affinity-low-capacity-and-low-affinity-high-capacity-n-acetyl-2-aminofluorene-aaf-macromolecular-binding-sites-are-revealed-during-the-growth-cycle-of-adult-rat-hepatocytes-in-primary-culture
#16
K S Koch, T Moran, W T Shier, H L Leffert
Long-term cultures of primary adult rat hepatocytes were used to study the effects of N-acetyl-2-aminofluorene (AAF) on hepatocyte proliferation during the growth cycle; on the initiation of hepatocyte DNA synthesis in quiescent cultures; and, on hepatocyte DNA replication following the initiation of DNA synthesis. Scatchard analyses were used to identify the pharmacologic properties of radiolabeled AAF metabolite binding to hepatocyte macromolecules. Two classes of growth cycle-dependent AAF metabolite binding sites - a high-affinity low-capacity site (designated Site I) and a low-affinity high-capacity site (designated Site II) - associated with two spatially distinct classes of macromolecular targets, were revealed...
January 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29319795/n-acetyl-2-aminofluorene-aaf-processing-in-adult-rat-hepatocytes-in-primary-culture-occurs-by-high-affinity-low-velocity-and-low-affinity-high-velocity-aaf-metabolite-forming-systems
#17
K S Koch, T Moran, W T Shier, H L Leffert
N-acetyl-2-aminofluorene (AAF) is a procarcinogen used widely in physiological investigations of chemical hepatocarcinogenesis. Its metabolic pathways have been described extensively, yet little is known about its biochemical processing, growth cycle expression and pharmacological properties inside living hepatocytes - the principal cellular targets of this hepatocarcinogen. In this report, primary monolayer adult rat hepatocyte cultures and high specific-activity [ring G-3H]-N-acetyl-2-aminofluorene were used to extend previous observations of metabolic activation of AAF by highly differentiated, proliferation-competent hepatocytes in long-term cultures...
January 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29318023/microbiome-and-asthma
#18
REVIEW
Milena Sokolowska, Remo Frei, Nonhlanhla Lunjani, Cezmi A Akdis, Liam O'Mahony
The mucosal immune system is in constant communication with the vast diversity of microbes present on body surfaces. The discovery of novel molecular mechanisms, which mediate host-microbe communication, have highlighted the important roles played by microbes in influencing mucosal immune responses. Dendritic cells, epithelial cells, ILCs, T regulatory cells, effector lymphocytes, NKT cells and B cells can all be influenced by the microbiome. Many of the mechanisms being described are bacterial strain- or metabolite-specific...
2018: Asthma research and practice
https://www.readbyqxmd.com/read/29317722/loss-of-the-mitochondrial-fatty-acid-%C3%AE-oxidation-protein-medium-chain-acyl-coenzyme-a-dehydrogenase-disrupts-oxidative-phosphorylation-protein-complex-stability-and-function
#19
Sze Chern Lim, Makiko Tajika, Masaru Shimura, Kirstyn T Carey, David A Stroud, Kei Murayama, Akira Ohtake, Matthew McKenzie
Medium-chain acyl-Coenzyme A dehydrogenase (MCAD) is involved in the initial step of mitochondrial fatty acid β-oxidation (FAO). Loss of function results in MCAD deficiency, a disorder that usually presents in childhood with hypoketotic hypoglycemia, vomiting and lethargy. While the disruption of mitochondrial fatty acid metabolism is the primary metabolic defect, secondary defects in mitochondrial oxidative phosphorylation (OXPHOS) may also contribute to disease pathogenesis. Therefore, we examined OXPHOS activity and stability in MCAD-deficient patient fibroblasts that have no detectable MCAD protein...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317520/atm-directs-dna-damage-responses-and-proteostasis-via-genetically-separable-pathways
#20
Ji-Hoon Lee, Michael R Mand, Chung-Hsuan Kao, Yi Zhou, Seung W Ryu, Alicia L Richards, Joshua J Coon, Tanya T Paull
The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated the activation of ATM by DNA damage from that by oxidative stress using separation-of-function mutations. We found that deficient activation of ATM by the Mre11-Rad50-Nbs1 complex and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage...
January 9, 2018: Science Signaling
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