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Immune metabolism

Nishant Saxena, Jeseong Won, Seungho Choi, Avtar K Singh, Inderjit Singh
We previously reported that S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, attenuated TH 17-mediated immune responses in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Cellular GSNO homeostasis is regulated via its synthesis by reaction between nitric oxide and glutathione and its enzymatic catabolism by GSNO reductase (GSNOR). In this study, we evaluated potential of reversible inhibitor of GSNOR (N6022) in comparison with exogenous GSNO in immunopathogenesis of EAE...
April 22, 2018: Free Radical Biology & Medicine
Murali Ganesan, Irina Tikhanovich, Shiva Shankar Vangimalla, Raghubendra Singh Dagur, Weimin Wang, Larisa I Poluektova, Yimin Sun, David F Mercer, Dean Tuma, Steven A Weinman, Kusum K Kharbanda, Natalia A Osna
Background & Aims: Alcohol-induced progression of hepatitis C virus (HCV) infection is related to dysfunction of innate immunity in hepatocytes. Endogenously produced interferon (IFN)α induces activation of interferon-stimulated genes (ISGs) via triggering of the Janus kinase-signal transducer and activator of transcription 1 (STAT1) pathway. This activation requires protein methyltransferase 1-regulated arginine methylation of STAT1. Here, we aimed to study whether STAT1 methylation also depended on the levels of demethylase jumonji domain-containing 6 protein (JMJD6) and whether ethanol and HCV affect JMJD6 expression in hepatocytes...
2018: Cellular and Molecular Gastroenterology and Hepatology
C-C Chao, B O Ingram, W Lurchachaiwong, W-M Ching
Scrub typhus is an acute zoonosis caused by the obligate intracellular Gram-negative bacterium Orientia tsutsugamushi. To better understand the host response elicited by natural infection by chigger feeding, ICR mice were infected by Leptotrombidium chiangraiensis (Lc1) chiggers, and the metabolic profiles of their serum were examined over several time points after initiation of feeding. ICR mice were infected by either naive Lc1 chiggers (i.e. not infected by O. tsutsugamushi, NLc1) or O. tsutsugamushi -infected Lc1 chiggers (OLc1)...
May 2018: New Microbes and New Infections
Yan Cheng, Cátia Monteiro, Andreia Matos, Jiaying You, Avelino Fraga, Carina Pereira, Victoria Catalán, Amaia Rodríguez, Javier Gómez-Ambrosi, Gema Frühbeck, Ricardo Ribeiro, Pingzhao Hu
Background: Periprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients. DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI > 25 kg m-2 ) and normal weight (NW, BMI < 25 kg m-2 ) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling...
2018: Clinical Epigenetics
Jay D Evans, Qiang Huang
We previously identified microRNA (miRNA) from Nosema ceranae and found that knockdowns of transcripts for the parasite protein Dicer greatly reduce parasite reproduction. In order to study parasitic miRNA functions and identify candidate target genes, we fed honey bees infected with N. ceranae with small interfering RNA (siRNA) targeting the N. ceranae gene Dicer . We then deep-sequenced honey bee and N. ceranae miRNAs daily across a full 6-day proliferation cycle. We found seven honey bee and five N. ceranae miRNAs that were significantly differently expressed between the infection and siRNA-Dicer groups...
2018: Frontiers in Microbiology
Stefania Cantore, Vito Crincoli, Antonio Boccaccio, Antonio Emmanuele Uva, Michele Fiorentino, Giuseppe Monno, Patrizio Bollero, Chiara Derla, Francesca Fabiano, Andrea Ballini, Luigi Santacroce
BACKGROUND: New sources of stem cells in adult organisms are constantly emerging. Postnatal Mesenchymal Stem Cells (MSCs), are the most promising support to perform an effective regenerative medicine: such cells have the ability to differentiate into several lineages, such as osteoblasts and chondroblasts, providing novel strategies to improve different complex treatments, during bone regeneration. 3D-printed biomaterials can be designed with geometry aimed to induce stem cells to differentiate towards specific lineage...
April 22, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
Wilfred C de Vega, Lauren Erdman, Suzanne D Vernon, Anna Goldenberg, Patrick O McGowan
AIM: To identify subtypes in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) based on DNA methylation profiles and health scores. METHODS: DNA methylome profiles in immune cells were integrated with symptomatology from 70 women with ME/CFS using similarity network fusion to identify subtypes. RESULTS: We discovered four ME/CFS subtypes associated with DNA methylation modifications in 1939 CpG sites, three RAND-36 categories and five DePaul Symptom Questionnaire measures...
April 25, 2018: Epigenomics
Lucas B Rizzo, Walter Swardfager, Pawan Kumar Maurya, Maiara Zeni Graiff, Mariana Pedrini, Elson Asevedo, Ana Cláudia Cassinelli, Moisés E Bauer, Quirino Cordeiro, Jan Scott, Elisa Brietzke, Hugo Cogo-Moreira
OBJECTIVES: The study aims to generate an immunological age (IA) trait on the basis of immune cell differentiation parameters, and to test whether the IA is related to age and disease characteristics. METHODS: Forty-four euthymic type I bipolar disorder patients were included in this study. Five immunosenescence-related parameters were assessed: proportions of late-differentiated cells (e.g., CD3+CD8+CD28-CD27- and CD3-CD19+IgD-CD27-), and the expression of CD69, CD71, and CD152 after stimulation...
April 25, 2018: International Journal of Methods in Psychiatric Research
Pravin Kesarwani, Antony Prabhu, Shiva Kant, Praveen Kumar, Stewart F Graham, Katie L Buelow, George D Wilson, Christopher Ryan Miller, Prakash Chinnaiyan
PURPOSE: Immune checkpoint inhibitors designed to revert tumor-induced immune suppression have emerged as potent anti-cancer therapies. Tryptophan metabolism represents an immune checkpoint and targeting this pathway's rate limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary metabolism of tryptophan metabolism in glioblastoma and evaluated the activity of the IDO1 inhibitor GDC-0919, both alone and in combination with radiation (RT).  Experimental Design: LC/GC-MS and expression profiling was performed for metabolomic and genomic analyses of patient-derived glioma...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sinian Li, Yiming Shao, Kanglan Li, Changmei HuangFu, Wenjie Wang, Zhou Liu, Zhiyou Cai, Bin Zhao
Vascular cognitive impairment (VCI), the second most common cause of dementia in elderly people, is a term that refers to all forms of cognitive disorders that can be attributed to cerebrovascular disease such as manifestations of discrete infarctions, brain hemorrhages, and white matter lesions. The gut microbiota (GM) has emerged recently as an essential player in the development of VCI. The GM may affect the brain's physiological, behavioral, and cognitive functions through the brain-gut axis via neural, immune, endocrine, and metabolic pathways...
April 17, 2018: Journal of Alzheimer's Disease: JAD
Jesse Hornstein, Emmanuelle Pales Espinosa, Robert M Cerrato, Kamazima M M Lwiza, Bassem Allam
Atlantic surfclam populations have significantly declined in state and federal waters from the south shore of Long Island, New York to the Delmarva Peninsula since the early 2000s. Previous studies have demonstrated that surfclams in this geographic range show signs of physiological stress, suggested to be a result of increasing ocean temperatures. In this study, we examined the effect of 2 temperature regimes (19 °C and 23 °C) on surfclam physiology. These temperatures were chosen because they represent maximal (23 °C) and minimal (19 °C) temperatures prevailing in New York clamming areas during summer...
April 21, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Phyu Thwe, Eyal Amiel
In the field of immunology, there is an increasing interest in cellular energy metabolism and its outcome on immune cell effector function. Activation of immune cells leads to rapid metabolic changes that are central to cellular biology in order to support the effector responses. Therefore, the need for user-friendly and dependable assay technologies to address metabolic regulation and nutrient utilization in immune cells is an important need in this field. Redox-dye reduction-based Phenotype MicroArray (PM) assays, which measure NADH reduction as a readout, developed by Biolog Inc...
April 21, 2018: Journal of Immunological Methods
Ryan Lusk, Laura M Saba, Lauren A Vanderlinden, Vaclav Zidek, Jan Silhavy, Michal Pravenec, Paula L Hoffman, Boris Tabakoff
BACKGROUND: A statistical pipeline was developed and used for determining candidate genes and candidate gene co-expression networks involved in two alcohol (i.e., ethanol) metabolism phenotypes, namely alcohol clearance and acetate area under the curve (AUC) in a recombinant inbred (HXB/BXH) rat panel. The approach was also used to provide an indication of how ethanol metabolism can impact the normal function of the identified networks. METHODS: RNA was extracted from alcohol-naïve liver tissue of 30 strains of HXB/BXH recombinant inbred rats...
April 24, 2018: Alcoholism, Clinical and Experimental Research
Louise O'Rourke, Gerard Clarke, Aoife Nolan, Claire Watkins, Timothy G Dinan, Catherine Stanton, R Paul Ross, Cornelius Anthony Ryan
Breast milk is the only source of the essential amino acid tryptophan (TRP) in breast-fed infants. Low levels of TRP could have implications for infant neurodevelopment. The objectives of the present study were to compare the relationship of TRP and its neuroactive pathway metabolites kynurenine (Kyn) and kynurenic acid (KynA) in preterm and term expressed breast milk (EBM) in the first 14 d following birth, and the relationship of TRP metabolism to maternal stress and immune status. A total of twenty-four mothers were recruited from Cork University Maternity Hospital: twelve term (>38 weeks) and twelve preterm (<35 weeks)...
2018: Journal of Nutritional Science
Andrea Quagliariello, Federica Del Chierico, Alessandra Russo, Sofia Reddel, Giulia Conte, Loris R Lopetuso, Gianluca Ianiro, Bruno Dallapiccola, Francesco Cardona, Antonio Gasbarrini, Lorenza Putignani
Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology...
2018: Frontiers in Microbiology
Yoshitomo Hayama, Tetsuya Kimura, Yoshito Takeda, Shigeyuki Nada, Shohei Koyama, Hyota Takamatsu, Sujin Kang, Daisuke Ito, Yohei Maeda, Masayuki Nishide, Satoshi Nojima, Hana Sarashina-Kida, Takashi Hosokawa, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Yoshimitsu Nakanishi, Takeshi Tsuda, Taro Koba, Masato Okada, Atsushi Kumanogoh
Amino acid metabolism plays important roles in innate immune cells, including macrophages. Recently, we reported that a lysosomal adaptor protein, Lamtor1, which serves as the scaffold for amino acid-activated mechanistic target of rapamycin complex 1 (mTORC1), is critical for the polarization of M2 macrophages. However, little is known about how Lamtor1 affects the inflammatory responses that are triggered by the stimuli for TLRs. In this article, we show that Lamtor1 controls innate immune responses by regulating the phosphorylation and nuclear translocation of transcription factor EB (TFEB), which has been known as the master regulator for lysosome and autophagosome biogenesis...
April 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Henrik M Hammarén, Anniina T Virtanen, Juuli Raivola, Olli Silvennoinen
The JAK-STAT signal transduction pathway is responsible for mediating signals of over fifty cytokines, growth factors and hormones. Signaling through the JAK-STAT pathway is regulated on multiple levels, including intramolecular regulation by the JAK pseudokinase domain, and intermolecular regulation by a host of regulatory proteins. The advent of accessible genomic tools have provided a wealth of information on disease-associated mutations in the JAK-STAT pathway and its regulatory components. The vast number of these mutations in diseases ranging from immunodeficiencies and obesity to many cancers highlight the importance of correct regulation of JAK-STAT signaling for biological processes such as hematopoiesis, regulation of the immune system, metabolism, and growth...
April 20, 2018: Cytokine
Shi-Mei Lin, Chao-Ming Shi, Ming-Ming Mu, Yong-Jun Chen, Li Luo
An experimental trial was conducted to investigate the effects of high dietary starch levels on growth, hepatic glucose metabolism enzyme, antioxidant capacity and immune responses of largemouth bass, Micropterus salmoides. Fish (initial body weight: 16.9 ± 0.24 g) were fed three isonitrogenous and isoenergetic semi-purified diets containing 5%, 10% and 20% wheat starch, respectively. The results indicated that fish fed 5% and 10% starch diets showed significantly better weight gain, specific growth rate (SGR), protein efficiency ratio (PER) and feed conversion ratio (FCR) compared with that fed 20% starch diet...
April 20, 2018: Fish & Shellfish Immunology
Qinwei Yu, Zhenzhou Jiang, Luyong Zhang
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat deposition in the liver in the absence of significant alcohol consumption. Dysregulated bile acid (BA) metabolism is an important indicator in the pathology of NAFLD, which could progress into more severe forms of liver injury. Lipid metabolism, immune environment and intestinal bacteria are all affected by dysregulated BA metabolism directly, but the mechanisms remain unclear. Several drug candidates that target BA metabolism, either used alone or in combination with other agents, are currently under development for treatment of NAFLD...
April 20, 2018: Pharmacology & Therapeutics
Daniel Lancour, Adam Naj, Richard Mayeux, Jonathan L Haines, Margaret A Pericak-Vance, Gerard C Schellenberg, Mark Crovella, Lindsay A Farrer, Simon Kasif
Improving accuracy in genetic studies would greatly accelerate understanding the genetic basis of complex diseases. One approach to achieve such an improvement for risk variants identified by the genome wide association study (GWAS) approach is to incorporate previously known biology when screening variants across the genome. We developed a simple approach for improving the prioritization of candidate disease genes that incorporates a network diffusion of scores from known disease genes using a protein network and a novel integration with GWAS risk scores, and tested this approach on a large Alzheimer disease (AD) GWAS dataset...
April 23, 2018: PLoS Genetics
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