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https://www.readbyqxmd.com/read/28089782/hepatic-co-cultures-in-vitro-reveal-suitable-to-detect-nrf2-mediated-oxidative-stress-responses-on-the-bladder-carcinogen-o-anisidine
#1
Franziska Wewering, Florent Jouy, Sükran Caliskan, Stefan Kalkhof, Martin von Bergen, Andreas Luch, Sebastian Zellmer
The azo dye o-anisidine is known as an industrial and environmental pollutant. Metabolites of o-anisidine remain in the liver for >24h. However, the toxicological impact of o-anisidine on the liver and its individual cell types, e.g., hepatocytes and immune cells, is currently poorly understood. A novel co-culture system, composed of HepG2 or Huh-7 cells, and differentiated THP-1 cells was used to study the metabolic capacity towards o-anisidine, and compared to primary murine hepatocytes which express high enzyme activities...
January 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28077630/mavs-is-essential-for-primary-cd4-t-cell-immunity-but-not-for-recall-t-cell-responses-following-an-attenuated-west-nile-virus-infection
#2
Huanle Luo, Evandro Winkelmann, Guorui Xie, Rong Fang, Bi-Hung Peng, Li Li, Helen M Lazear, Slobodan Paessler, Michael S Diamond, Michael Gale, Alan D Barrett, Tian Wang
: The use of pathogen recognition receptor (PRR) agonists and the molecular mechanisms involved have been the major focus of research in individual vaccine development. West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant has several features for an ideal vaccine candidate, including significantly reduced neuroinvasiveness, induction of strong adaptive immunity, and protection of mice from wild-type (WT) WNV infection. Here, we determined the role of mitochondrial antiviral-signaling (MAVS), the adaptor protein for RIG-I like receptor in regulating host immunity against the NS4B-P38G vaccine...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077274/the-role-and-regulation-of-the-peroxisome-proliferator-activated-receptor-alpha-in-human-liver
#3
REVIEW
Sander Kersten, Rinke Stienstra
The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice have shown that PPARα serves as the master regulator of hepatic lipid metabolism during fasting. In addition, PPARα suppresses inflammation and the acute phase response. Comparatively little is known about PPARα in human liver...
January 7, 2017: Biochimie
https://www.readbyqxmd.com/read/28073693/crosstalk-between-cytoplasmic-rig-i-and-sting-sensing-pathways
#4
REVIEW
Alessandra Zevini, David Olagnier, John Hiscott
Detection of evolutionarily conserved molecules on microbial pathogens by host immune sensors represents the initial trigger of the immune response against infection. Cytosolic receptors sense viral and intracellular bacterial genomes, as well as nucleic acids produced during replication. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Although distinct classes of receptors are responsible for the RNA and DNA sensing, the downstream signaling components are physically and functionally interconnected...
January 7, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28069950/chronic-innate-immune-activation-of-tbk1-suppresses-mtorc1-activity-and-dysregulates-cellular-metabolism
#5
Maroof Hasan, Vijay K Gonugunta, Nicole Dobbs, Aktar Ali, Guillermo Palchik, Maria A Calvaruso, Ralph J DeBerardinis, Nan Yan
Three-prime repair exonuclease 1 knockout (Trex1(-/-)) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1(-/-) mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069354/bufadienolides-from-amphibians-a-promising-source-of-anticancer-prototypes-for-radical-innovation-apoptosis-triggering-and-na-k-atpase-inhibition
#6
REVIEW
Lívia Queiroz de Sousa, Kátia da Conceição Machado, Samara Ferreira de Carvalho Oliveira, Lidiane da Silva Araújo, Evaldo Dos Santos Monção-Filho, Ana Amélia de Carvalho Melo-Cavalcante, Gerardo Magela Vieira-Júnior, Paulo Michel Pinheiro Ferreira
Amphibians present pharmacologically active aliphatic, aromatic and heterocyclic molecules in their skin as defense against microorganisms, predators and infections, such as steroids, alkaloids, biogenic amines, guanidine derivatives, proteins and peptides. Based on the discovered bioactive potential of bufadienolides, this work reviewed the contribution of amphibians, especially from members of Bufonidae family, as source of new cytotoxic and antitumor molecules, highlighting the mechanisms responsible for such amazing biological potentialities...
January 6, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28068941/looking-beyond-the-brain-to-improve-the-pathogenic-understanding-of-parkinson-s-disease-implications-of-whole-transcriptome-profiling-of-patients-skin
#7
Anu Planken, Lille Kurvits, Ene Reimann, Liis Kadastik-Eerme, Külli Kingo, Sulev Kõks, Pille Taba
BACKGROUND: Parkinson's Disease is a progressive neurodegenerative disease, characterized by symptoms of motor impairment, resulting from the loss of dopaminergic neurons in the midbrain, however non-neuronal symptoms are also common. Although great advances have been made in the pathogenic understanding of Parkinson's Disease in the nervous system, little is known about the molecular alterations occurring in other non-neuronal organ systems. In addition, a higher rate of melanoma and non-melanoma skin cancer has been observed in the Parkinson's Disease population, indicating crosstalk between these diseases...
January 10, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28064018/alterations-in-nitric-oxide-homeostasis-during-traumatic-brain-injury
#8
REVIEW
Andrey V Kozlov, Soheyl Bahrami, Heinz Redl, Csaba Szabo
Changes in nitric oxide (NO) levels have been often associated with various forms of trauma, including secondary damage after traumatic brain injury (TBI). Several studies demonstrate the upregulation of NO synthase (NOS) enzymes, and concomitant increases in brain NO levels, which contribute to the TBI-associated glutamate cytotoxicity, including the pathogenesis of mitochondrial dysfunction. TBI is also associated with elevated NO levels in remote organs, indicating that TBI can induce systemic changes in NO regulation, which can be either beneficial or detrimental...
January 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28063496/measuring-phospholipase-d-enzymatic-activity-through-biochemical-and-imaging-methods
#9
F Philip, E E Ha, M A Seeliger, M A Frohman
The phospholipase D (PLD) enzymatic superfamily regulates a wide range of cell biological and physiological pathways, including platelet activation, immune responses, cancer, and spermatogenesis. The three main enzymatic actions of the superfamily entail (i) hydrolyzing membrane phospholipids (phosphatidylcholine (PC) and cardiolipin) to generate choline and the second messenger signaling lipid phosphatidic acid (PA), (ii) using ethanol to transphosphatidylate PC to generate the long-lived metabolite phosphatidylethanol, and (iii) hydrolyzing RNA transcripts to generate piRNAs, the third form of endogenous RNAi...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28059524/antileishmanial-activity-of-pyrazolopyridine-derivatives-and-their-potential-as-adjunct-therapy-with-miltefosine
#10
Devireddy Anand, Pawan Kumar Yadav, Om P S Patel, Naveen Parmar, Rahul K Maurya, Preeti Vishwakarma, Kanumuri S R Raju, Isha Taneja, Muhammad Wahajuddin, Susanta Kar, Prem P Yadav
A series of pyrazolo(dihydro)pyridines were synthesized and evaluated for antileishmanial efficacy against experimental visceral leishmaniasis. Among all, compounds 6d and 6j exhibited better activity than miltefosine against the intracellular amastigotes. Compound 6j (50 mg/kg/day) was further studied against Leishmania donovani/BALB/c mice via the intraperitoneal route for 5 days and displayed >91 and >93% clearances in splenic and liver parasitic burden, respectively. Combination treatment of 6j with the sub-curative dose of miltefosine (5 mg/kg) in BALB/c mice almost completely ameliorated the disease (>97% inhibition) by augmenting nitric oxide generation and shifting the immune response towards Th1 mode...
January 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28057759/potent-nlrp3-inflammasome-activation-by-the-hiv-reverse-transcriptase-inhibitor-abacavir
#11
Atiye Toksoy, Helga Sennefelder, Christian Adam, Sonja Hofmann, Axel Trautmann, Matthias Goebeler, Marc Schmidt
There is experimental and clinical evidence that some exanthematous allergic drug hypersensitivity reactions are mediated by drug-specific T cells. We hypothesized that the capacity of certain drugs to directly stimulate the innate immune system may contribute to generate drug-specific T cells. Here we analyzed whether abacavir, an HIV-1 reverse transcriptase inhibitor often inducing severe delayed-type drug hypersensitivity, can trigger innate immune activation that may contribute to its allergic potential...
January 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28056786/immune-adaptation-to-chronic-intense-exercise-training-new-microarray-evidence
#12
Dongmei Liu, Ru Wang, Ana R Grant, Jinming Zhang, Paul M Gordon, Yuqin Wei, Peijie Chen
BACKGROUND: Endurance exercise training, especially the high-intensity training, exhibits a strong influence on the immune system. However, the mechanisms underpinning the immune-regulatory effect of exercise remain unclear. Consequently, we chose to investigate the alterations in the transcriptional profile of blood leukocytes in young endurance athletes as compared with healthy sedentary controls, using Affymetrix human gene 1.1 ST array. RESULTS: Group differences in the transcriptome were analyzed using Intensity-based Hierarchical Bayes method followed by a Logistic Regression-based gene set enrichment method...
January 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28055957/analysis-of-molecular-mechanisms-of-5-fluorouracil-induced-steatosis-and-inflammation-in-vitro-and-in-mice
#13
Judith Sommer, Abdo Mahli, Kim Freese, Tobias S Schiergens, Fulya Suzan Kuecuekoktay, Andreas Teufel, Wolfgang E Thasler, Martina Müller, Anja K Bosserhoff, Claus Hellerbrand
Chemotherapy-associated steatohepatitis is attracting increasing attention because it heralds an increased risk of morbidity and mortality in patients undergoing surgery because of liver metastases. The aim of this study was to develop in vitro and in vivo models to analyze the pathogenesis of 5-fluorouracil (5-FU)-induced steatohepatitis.Therefore, primary human hepatocytes and HepG2 hepatoma cells were incubated with 5-FU at non-toxic concentrations up to 24 h. Furthermore, hepatic tissue of C57BL/6N mice was analyzed 24 h after application of a single 5-FU dose (200 mg/kg body weight)...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029694/type-i-interferons-mediate-the-neuroinflammatory-response-and-neurotoxicity-induced-by-rotenone
#14
Bevan S Main, Moses Zhang, Kate M Brody, Francis J Kirby, Peter J Crack, Juliet M Taylor
Evidence from post-mortem human brains, animal studies and cell culture models has implicated neuroinflammation in the aetiology of chronic neuropathologies including Alzheimer's and Parkinson's diseases. Although the neuroinflammatory response is considered detrimental in contributing to these pathologies, the underlying mechanisms are still not well understood. The type-I interferons (IFNs) have been well characterised in the periphery and are known to initiate/modulate the immune response. Recently, they have been implicated in aging and we have also demonstrated increased type-I IFN expression in post-mortem human Alzheimer's and Parkinson's disease brains...
December 28, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28029652/tumor-suppressor-blu-promotes-trail-induced-apoptosis-by-downregulating-nf-%C3%AE%C2%BAb-signaling-in-nasopharyngeal-carcinoma
#15
Jiahui Zhou, Zunnan Huang, Ziyou Wang, Shumin Liu, Alf Grandien, Ingemar Ernberg, Zhiwei He, Xiangning Zhang
A putative tumor suppressor BLU mapped on the chromosomal 3p21 region, is frequently lost in human tumors including nasopharyngeal carcinoma (NPC). To explore the underlying mechanism of tumor suppression by BLU, its potential to promote apoptosis induced by TRAIL, an effector molecule elaborated by natural killer-T (NKT) cells was investigated. BLU was re-expressed in NPC-derived HNE1 cells by recombinant adenoviral infection and the cells were challenged with recombinant TRAIL. The growth inhibition of BLU was assayed and apoptosis was examined by flow cytometry-based tetramethylrhodamine ethyl ester (TMRE) and annexin V staining, cleavage of pro-caspase-8 and poly ADP ribose polymerase (PARP)...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28013001/mitochondrial-functions-of-thp-1-monocytes-following-the-exposure-to-selected-natural-compounds
#16
Nadin Schultze, Heike Wanka, Paula Zwicker, Ulrike Lindequist, Beate Haertel
The immune system is an important target of various xenobiotics, which may lead to severe adverse effects including immunosuppression or inappropriate immunostimulation. Mitochondrial toxicity is one possibility by which xenobiotics exert their toxic effects in cells or organs. In this study, we investigated the impact of three natural compounds, cyclosporine A (CsA), deoxynivalenol (DON) and cannabidiol (CBD) on mitochondrial functions in the THP-1 monocytic cell line. The cells were exposed for 24h to two different concentrations (IC10 and IC50 determined by MTT) of each compound...
December 21, 2016: Toxicology
https://www.readbyqxmd.com/read/28008133/scolopendin-an-antimicrobial-peptide-from-centipede-attenuates-mitochondrial-functions-and-triggers-apoptosis-in-candida-albicans
#17
Heejeong Lee, Jae-Sam Hwang, Dong Gun Lee
Centipedes, a type of arthropod, reportedly produce antimicrobial peptides as part of an innate immune response. Scolopendin (SPSEKAGLQPVGRIGRMLKK) is a novel antimicrobial peptide derived from Scolopendra subspinipes mutilans Many antifungal agents have more than one type of cell death mechanism. Although scolopendin is involved in membrane perturbation, the corresponding intracellular changes require further investigation. Therefore, we assessed the cell morphology and calcium ion concentration of the cytosol and mitochondria of scolopendin-treated cells...
December 22, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/28004928/iterative-design-and-in-vivo-evaluation-of-an-oncolytic-antilymphoma-peptide
#18
J Johannes Eksteen, Dominik Ausbacher, Jaione Simon-Santamaria, Trine Stiberg, Cristiane Cavalcanti-Jacobsen, Imin Wushur, John S Svendsen, Øystein Rekdal
Oncolytic peptides represent a promising new strategy within the field of cancer immunotherapy. Here we describe the systematic design and evaluation of short antilymphoma peptides within this paradigm. The peptides were tested in vitro and in vivo to identify a lead compound for further evaluation as novel oncolytic immunotherapeutic. In vitro tests revealed peptides with high activity against several lymphoma types and low cytotoxicity toward normal cells. Treated lymphoma cells exhibited a reduced mitochondrial membrane potential that resulted in an irreversible disintegration of their plasma membranes...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28003373/chronic-inflammation-accelerator-of-biological-aging
#19
REVIEW
Bertrand Fougère, Eric Boulanger, Fati Nourhashémi, Sophie Guyonnet, Matteo Cesari
Biological aging is characterized by a chronic low-grade inflammation level. This chronic phenomenon has been named "inflamm-aging" and is a highly significant risk factor for morbidity and mortality in the older persons. The most common theories of inflamm-aging include redox stress, mitochondrial dysfunction, glycation, deregulation of the immune system, hormonal changes, epigenetic modifications, and dysfunction telomere attrition. Inflamm-aging plays a role in the initiation and progression of age-related diseases such as type II diabetes, Alzheimer's disease, cardiovascular disease, frailty, sarcopenia, osteoporosis, and cancer...
December 21, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28001907/ionizing-radiation-induces-innate-immune-responses-in-macrophages-by-generation-of-mitochondrial-reactive-oxygen-species
#20
Sup Kim, Jin Ho Choe, Gippeum Joy Lee, Yi Sak Kim, Soo Yeon Kim, Hye-Mi Lee, Hyo Sun Jin, Tae Sung Kim, Jin-Man Kim, Moon-June Cho, Eui-Cheol Shin, Eun-Kyeong Jo, Jun-Sang Kim
During radiotherapy for tumors, the innate immune system also responds to ionizing radiation and induces immune modulation. However, little is known about the molecular mechanisms by which radiation modulates innate immune responses. In this study, we observed that radiation triggered the generation of mitochondrial reactive oxygen species (mROS), leading to innate immune responses in murine bone marrow-derived macrophages (BMDM). Radiation-induced mROS was essential for robust induction of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-12p40 mRNA and protein in BMDM...
December 21, 2016: Radiation Research
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