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https://www.readbyqxmd.com/read/29351393/liver-tissue-metabolically-transformed-by-alcohol-induces-immune-recognition-of-liver-self-proteins-but-not-in-vivo-inflammation
#1
Michael J Duryee, Benjamin M Wiese, Jordan R Bowman, Jared D Vanlandingham, Lynell W Klassen, Geoffrey E Thiele, Carlos D Hunter, Daniel R Anderson, Ted R Mikuls, Geoffrey M Thiele
Precision cut liver slices (PCLSs) provide a novel model for studies in alcoholic liver disease (ALD). This is relevant, as in vivo ethanol exposure does not appear to generate significant liver damage in ethanol fed mice, except in the NIAAA binge model of ALD. Previous studies have shown that the two metabolites of ethanol consumption, malondialdhyde (MDA) and acetaldehyde (AA), combine to form (MAA), which has been correlated with the development and progression of ALD. In this study murine PCLSs were incubated with ethanol and examined for the production of MAA...
December 28, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29351335/the-effects-of-an-acute-exercise-bout-on-gh-and-igf-1-in-prediabetic-and-healthy-african-americans-a-pilot-study-investigating-gene-expression
#2
Nathaniel T Berry, Monica Hubal, Laurie Wideman
The incidence of pre-diabetes (PD) and Type-2 Diabetes Mellitus (T2D) is a worldwide epidemic. African American (AA) individuals are disproportionately more likely to become diabetic than other ethnic groups. Over the long-term, metabolic complications related to diabetes result in significant alterations in growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Considering the limited exercise-related studies in the area of gene expression changes with disease progression, the objective of this study was to examine differences in exercise-induced gene expression related to the GH and IGF-1 pathways in peripheral blood mononuclear cells (PBMCs) of healthy (CON) and PD AA individuals...
2018: PloS One
https://www.readbyqxmd.com/read/29350534/discovery-of-tetrahydroisoquinoline-containing-cxcr4-antagonists-with-improved-in-vitro-admet-properties
#3
Eric J Miller, Edgars Jecs, Valarie M Truax, Brooke M Katzman, Yesim A Tahirovic, Robert J Wilson, Katie M Kuo, Michelle B Kim, Huy H Nguyen, Manohar T Saindane, Huanyu Zhao, Tao Wang, Chi S Sum, Mary Ellen Cvijic, Gretchen M Schroeder, Lawrence J Wilson, Dennis C Liotta
CXCR4 is a 7-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by ≥ 48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4+ tumor cells from immune surveillance and chemotherapeutic elimination by 1) stimulating pro-survival signaling and 2) recruiting CXCR4+ immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4+ metastatic growths. Accordingly, CXCR4 antagonists can potentially obstruct CXCR4-mediated pro-survival signaling, recondition the CXCR4+ leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR4+ cancer cell metastasis...
January 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29349573/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-elevates-stimulus-evoked-release-of-dopamine-in-freely-moving-rats
#4
Juho-Matti Renko, Susanne Bäck, Merja H Voutilainen, T Petteri Piepponen, Ilkka Reenilä, Mart Saarma, Raimo K Tuominen
Neurotrophic factors (NTFs) hold potential as disease-modifying therapies for neurodegenerative disorders like Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), and mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown neuroprotective and restorative effects on nigral dopaminergic neurons in various animal models of Parkinson's disease. To date, however, their effects on brain neurochemistry have not been compared using in vivo microdialysis...
January 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29346757/p53-suppresses-metabolic-stress-induced-ferroptosis-in-cancer-cells
#5
Amy Tarangelo, Leslie Magtanong, Kathryn T Bieging-Rolett, Yang Li, Jiangbin Ye, Laura D Attardi, Scott J Dixon
How cancer cells respond to nutrient deprivation remains poorly understood. In certain cancer cells, deprivation of cystine induces a non-apoptotic, iron-dependent form of cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive transcription factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome editing, small-molecule probes, and high-resolution, time-lapse imaging, we find that stabilization of wild-type p53 delays the onset of ferroptosis in response to cystine deprivation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346507/activity-and-safety-of-afatinib-in-a-window-pre-operative-eortc-study-in-patients-with-squamous-cell-carcinoma-of-the-head-and-neck-scchn
#6
J P Machiels, P Bossi, J Menis, M Lia, C Fortpied, Y Liu, R Lhommel, M Lemort, S Schmitz, S Canevari, L De Cecco, M Guzzo, R Bianchi, P Quattrone, F Crippa, T Duprez, Y Lalami, M Quiriny, N de Saint Aubain, P M Clement, R Coropciuc, E Hauben, L F Licitra
Background: To investigate the activity and safety of afatinib in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5:1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were performed at diagnosis and just before surgery...
January 15, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29345370/inhibition-of-soluble-epoxide-hydrolase-attenuates-eosinophil-recruitment-and-food-allergen-induced-gastrointestinal-inflammation
#7
Idil Bastan, Xiao Na Ge, Mythili Dileepan, Yana G Greenberg, Alonso G Guedes, Sung Hee Hwang, Bruce D Hammock, Robert J Washabau, Savita P Rao, P Sriramarao
Prevalence of food allergies in the United States is on the rise. Eosinophils are recruited to the intestinal mucosa in substantial numbers in food allergen-driven gastrointestinal (GI) inflammation. Soluble epoxide hydrolase (sEH) is known to play a pro-inflammatory role during inflammation by metabolizing anti-inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory diols. We investigated the role of sEH in a murine model of food allergy and evaluated the potential therapeutic effect of a highly selective sEH inhibitor (trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]-cyclohexyloxy}-benzoic acid [t-TUCB])...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345342/high-fat-diet-and-leptin-promote-tumor-progression-by-inducing-myeloid-derived-suppressor-cells
#8
Virginia K Clements, Tiha Long, Ramses Long, Chas Figley, Daniel M C Smith, Suzanne Ostrand-Rosenberg
Obesity is a risk factor for cancer incidence and cancer mortality. The association of obesity and cancer is attributed to multiple factors, but the tightest linkage is with the chronic, low-grade inflammation that accompanies obesity. Myeloid-derived suppressor cells (MDSC) are known facilitators of cancer progression that act by suppressing the activation and function of tumor-reactive T cells. Because MDSC quantity and function are driven by chronic inflammation, we hypothesized that MDSC may accumulate in obese individuals and facilitate tumor growth by suppressing antitumor immunity...
January 3, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345219/transcriptional-changes-when-myxococcus-xanthus-preys-on-escherichia-coli-suggest-myxobacterial-predators-are-constitutively-toxic-but-regulate-their-feeding
#9
Paul G Livingstone, Andrew D Millard, Martin T Swain, David E Whitworth
Predation is a fundamental ecological process, but within most microbial ecosystems the molecular mechanisms of predation remain poorly understood. We investigated transcriptome changes associated with the predation of Escherichia coli by the myxobacterium Myxococcus xanthus using mRNA sequencing. Exposure to pre-killed prey significantly altered expression of 1319 predator genes. However, the transcriptional response to living prey was minimal, with only 12 genes being significantly up-regulated. The genes most induced by prey presence (kdpA and kdpB, members of the kdp regulon) were confirmed by reverse transcriptase quantitative PCR to be regulated by osmotic shock in M...
January 18, 2018: Microbial Genomics
https://www.readbyqxmd.com/read/29344645/targeted-disruption-of-adenosine-kinase-in-myeloid-monocyte-cells-increases-osteoclastogenesis-and-bone-resorption-in-mice
#10
Qiuying Ye, Ge Li, Shuhua Liu, Yalun Guan, Yunfeng Li, Jinling Li, Huanhuan Jia, Xuejiao Li, Qingnan Li, Ren Huang, Hui Wang, Yu Zhang
Adenosine kinase (ADK) serves an important role in intracellular adenosine clearance via phosphorylating adenosine to AMP. The role of adenosine and its receptors in the maintenance of bone homeostasis is well studied, particularly in osteoclastogenesis and bone resorption; however, the function of ADK in bone metabolism is still unclear. In the present study, utilizing the cre/floxp recombination system, mice with conditional loss of ADK function in myeloid monocyte cells were used to assess the effect of ADK deficiency on bone metabolism...
January 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29344085/synthesis-secretion-function-metabolism-and-application-of-natriuretic-peptides-in-heart-failure
#11
REVIEW
Shihui Fu, Ping Ping, Fengqi Wang, Leiming Luo
As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2...
2018: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29343683/hypoxia-inducible-factor-1%C3%AE-is-a-critical-transcription-factor-for-il-10-producing-b-cells-in-autoimmune-disease
#12
Xianyi Meng, Bettina Grötsch, Yubin Luo, Karl Xaver Knaup, Michael Sean Wiesener, Xiao-Xiang Chen, Jonathan Jantsch, Simon Fillatreau, Georg Schett, Aline Bozec
Hypoxia-inducible factors (HIFs) are key elements for controlling immune cell metabolism and functions. While HIFs are known to be involved in T cells and macrophages activation, their functions in B lymphocytes are poorly defined. Here, we show that hypoxia-inducible factor-1α (HIF-1α) contributes to IL-10 production by B cells. HIF-1α regulates IL-10 expression, and HIF-1α-dependent glycolysis facilitates CD1dhiCD5+ B cells expansion. Mice with B cell-specific deletion of Hif1a have reduced number of IL-10-producing B cells, which result in exacerbated collagen-induced arthritis and experimental autoimmune encephalomyelitis...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343435/paracrine-wnt5a-%C3%AE-catenin-signaling-triggers-a-metabolic-program-that-drives-dendritic-cell-tolerization
#13
Fei Zhao, Christine Xiao, Kathy S Evans, Tbalamayooran Theivanthiran, Nicholas DeVito, Alisha Holtzhausen, Juan Liu, Xiaojing Liu, David Boczkowski, Smita Nair, Jason W Locasale, Brent A Hanks
Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29342317/osteoblast-like-mc3t3-e1-cells-prefer-glycolysis-for-atp-production-but-adipocyte-like-3t3-l1-cells-prefer-oxidative-phosphorylation
#14
Anyonya R Guntur, Akos A Gerencser, Phuong T Le, Victoria E DeMambro, Sheila A Bornstein, Shona A Mookerjee, David E Maridas, David E Clemmons, Martin D Brand, Clifford J Rosen
Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate into osteoblasts, chondrocytes and adipocytes. We hypothesized that osteoblasts and adipocytes utilize distinct bioenergetic pathways during MSC differentiation. To test this hypothesis, we compared the bioenergetic profiles of pre-osteoblast MC3T3-E1 cells and calvarial osteoblasts with pre-adipocyte 3T3L1 cells, before and after differentiation. Differentiated MC3T3-E1 osteoblasts met ATP demand mainly by glycolysis with minimal reserve glycolytic capacity, whereas non-differentiated cells generated ATP through oxidative phosphorylation...
January 17, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29342173/hormone-induced-differential-transcriptome-analysis-of-sertoli-cells-during-postnatal-maturation-of-rat-testes
#15
Mukesh Gautam, Indrashis Bhattacharya, Umesh Rai, Subeer S Majumdar
Sertoli cells (Sc) are unique somatic cells of testis that are the target of both FSH and testosterone (T) and regulate spermatogenesis. Although Sc of neonatal rat testes are exposed to high levels of FSH and T, robust differentiation of spermatogonial cells becomes conspicuous only after 11-days of postnatal age. We have demonstrated earlier that a developmental switch in terms of hormonal responsiveness occurs in rat Sc at around 12 days of postnatal age during the rapid transition of spermatogonia A to B...
2018: PloS One
https://www.readbyqxmd.com/read/29342108/different-lipid-regulation-in-ovarian-cancer-inhibition-of-the-immune-system
#16
Christina Wefers, Tjitske Duiveman-de Boer, Petra L M Zusterzeel, Leon F A G Massuger, David Fuchs, Ruurd Torensma, Craig E Wheelock, I Jolanda M de Vries
Lipid metabolism is altered in several cancer settings leading to different ratios of intermediates. Ovarian cancer is the most lethal gynecological malignancy. Cancer cells disperse in the abdominal space and ascites occurs. T cells obtained from ascites are unable to proliferate after an antigenic stimulus. The proliferation of ascites-derived T cells can be restored after culturing the cells for ten days in normal culture medium. No pathway aberrancies were detected. The acellular fraction of ascites can inhibit the proliferation of autologous as well as allogeneic peripheral blood lymphocytes, indicating the presence of soluble factors that interfere with T cell functionality...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29340876/biomaterials-and-regenerative-medicine-in-urology
#17
N F Davis, E M Cunnane, M R Quinlan, J J Mulvihill, N Lawrentschuk, D M Bolton, M T Walsh
Autologous gastrointestinal tissue is the gold standard biomaterial for urinary tract reconstruction despite its long-term neuromechanical and metabolic complications. Regenerative biomaterials have been proposed as alternatives; however many are limited by a poor host derived regenerative response and deficient supportive elements for effective tissue regeneration in vivo. Urological biomaterials are sub-classified into xenogenic extracellular matrices (ECMs) or synthetic polymers. ECMs are decellularised, biocompatible, biodegradable biomaterials derived from animal organs...
January 17, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29340222/direct-molecular-fishing-of-new-protein-partners-for-human-thromboxane-synthase
#18
A V Svirid, P V Ershov, E O Yablokov, L A Kaluzhskiy, Yu V Mezentsev, A V Florinskaya, T A Sushko, N V Strushkevich, A A Gilep, S A Usanov, A E Medvedev, A S Ivanov
Thromboxane synthase (TBXAS1) catalyzes the isomerization reaction of prostaglandin H2 producing thromboxane A2, the autocrine and paracrine factor in many cell types. A high activity and metastability by these arachidonic acid derivatives suggests the existence of supramolecular structures that are involved in the regulation of the biosynthesis and directed translocation of thromboxane to the receptor. The objective of this study was to identify TBXAS1 protein partners from human liver tissue lysate using a complex approach based on the direct molecular fishing technique, LC-MS/MS protein identification, and protein-protein interaction validation by surface plasmon resonance (SPR)...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29339782/loss-of-disease-tolerance-during-citrobacter-rodentium-infection-is-associated-with-impaired-epithelial-differentiation-and-hyperactivation-of-t-cell-responses
#19
Eugene Kang, Guangyan Zhou, Mitra Yousefi, Romain Cayrol, Jianguo Xia, Samantha Gruenheid
Citrobacter rodentium is an intestinal mouse pathogen widely used as a model to study the mucosal response to infection. Inbred mouse strains suffer one of two fates following infection: self-limiting colitis or fatal diarrheal disease. We previously reported that Rspo2 is a major genetic determinant of the outcome of C. rodentium infection; Rspo2 induction during infection of susceptible mice leads to loss of intestinal function and mortality. Rspo2 induction does not impact bacterial colonization, but rather, impedes the ability of the host to tolerate C...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339767/regulatory-t-cells-trigger-effector-t-cell-dna-damage-and-senescence-caused-by-metabolic-competition
#20
Xia Liu, Wei Mo, Jian Ye, Lingyun Li, Yanping Zhang, Eddy C Hsueh, Daniel F Hoft, Guangyong Peng
Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to control Treg-induced effector T-cell senescence...
January 16, 2018: Nature Communications
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