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https://www.readbyqxmd.com/read/28211885/the-novel-bmi-1-inhibitor-ptc596-downregulates-mcl-1-and-induces-p53-independent-mitochondrial-apoptosis-in-acute-myeloid-leukemia-progenitor-cells
#1
Y Nishida, A Maeda, M J Kim, L Cao, Y Kubota, J Ishizawa, A AlRawi, Y Kato, A Iwama, M Fujisawa, K Matsue, M Weetall, M Dumble, M Andreeff, T W Davis, A Branstrom, S Kimura, K Kojima
Disease recurrence is the major problem in the treatment of acute myeloid leukemia (AML). Relapse is driven by leukemia stem cells, a chemoresistant subpopulation capable of re-establishing disease. Patients with p53 mutant AML are at an extremely high risk of relapse. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of AML stem cells. Here we studied the effects of a novel small molecule inhibitor of BMI-1, PTC596, in AML cells. Treatment with PTC596 reduced MCL-1 expression and triggered several molecular events consistent with induction of mitochondrial apoptosis: loss of mitochondrial membrane potential, BAX conformational change, caspase-3 cleavage and phosphatidylserine externalization...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28207838/viperin-interaction-with-mitochondrial-antiviral-signaling-protein-mavs-limits-viperin-mediated-inhibition-of-the-interferon-response-in-macrophages
#2
Jia Shee Hee, Peter Cresswell
Viperin is an antiviral protein that is upregulated by interferons and by ligands for a variety of innate immune receptors. It possesses diverse capabilities and functions in an array of viral infections. Studies have shown that it appears to be particularly important in defence against RNA viruses, such as West Nile, Dengue, and Chikungunya viruses, although the specific mechanisms involved are not well understood at the molecular level. Here we identify the mitochondrial antiviral signalling protein MAVS as a novel viperin interaction partner, most likely in mitochondria associated membranes, and characterize a more central, overarching role of viperin as a negative regulator of the interferon response, an ability that can be regulated by the viperin-MAVS interaction...
2017: PloS One
https://www.readbyqxmd.com/read/28206858/genetic-polymorphism-of-aedes-albopictus-population-inferred-from-nd5-gene-variabilities-in-subang-jaya-malaysia
#3
Nurul Adilah-Amrannudin, Mayamin Hamsidi, Nurul-Ain Ismail, Rodziah Ismail, Nazri Che Dom, Abu Hassan Ahmad, Mohd Fahmi Mastuki, Tengku Shahrul Anuar Tengku Ahmad Basri, Adira Khalid, Mohammad Muslim, Nurul Amalina Ahmad Daud, Siti Nazrina Camalxaman
This study was performed to establish the genetic variability of Aedes albopictus within Subang Jaya, Selangor, Malaysia, by using the nicotinamide adenine dinucleotide dehydrogenase 5 subunit (ND5) mitochondrial DNA (mtDNA) marker. A total of 90 samples were collected from 9 localities within an area of the Subang Jaya Municipality. Genetic variability was determined through the amplification and sequencing of a fragment of the ND5 gene. Eight distinct mtDNA haplotypes were identified. The evolutionary relationship of the local haplotypes alongside 28 reference strains was used to construct a phylogram, the analysis of which revealed low genetic differentiation in terms of both nucleotide and haplotype diversity...
December 2016: Journal of the American Mosquito Control Association
https://www.readbyqxmd.com/read/28181526/no-effect-of-mitochondrial-genotype-on-reproductive-plasticity-following-exposure-to-a-non-infectious-pathogen-challenge-in-female-or-male-drosophila
#4
M Nystrand, E J Cassidy, D K Dowling
Mitochondrial genetic variation shapes the expression of life-history traits associated with reproduction, development and survival, and has also been associated with the prevalence and progression of infectious bacteria and viruses in humans. The breadth of these effects on multifaceted components of health, and their link to disease susceptibility, led us to test whether variation across mitochondrial haplotypes affected reproductive success following an immune challenge in the form of a non-infectious pathogen...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174739/increased-mitochondrial-genetic-diversity-in-persons-infected-with-hepatitis-c-virus
#5
David S Campo, Ha-Jung Roh, Brian L Pearlman, Daniel S Fierer, Sumathi Ramachandran, Gilberto Vaughan, Andrew Hinds, Zoya Dimitrova, Pavel Skums, Yury Khudyakov
BACKGROUND & AIMS: The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression. METHODS: We evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28165481/targeting-mitochondrial-dysfunction-can-restore-antiviral-activity-of-exhausted-hbv-specific-cd8-t-cells-in-chronic-hepatitis-b
#6
Paola Fisicaro, Valeria Barili, Barbara Montanini, Greta Acerbi, Manuela Ferracin, Francesca Guerrieri, Debora Salerno, Carolina Boni, Marco Massari, M Cristina Cavallo, Glenda Grossi, Tiziana Giuberti, Pietro Lampertico, Gabriele Missale, Massimo Levrero, Simone Ottonello, Carlo Ferrari
Hepatitis B virus (HBV)-specific CD8 T cells are functionally exhausted in chronic hepatitis B infection, and this condition can be corrected only partially through the modulation of inhibitory pathways, which suggests that a more complex molecular interplay underlies T cell exhaustion. To gain broader insight into this process and identify additional targets for the restoration of T cell function, we compared the transcriptome profiles of HBV-specific CD8 T cells from patients with acute and chronic disease with those of HBV-specific CD8 T cells from patients able to resolve HBV infection spontaneously and influenza (FLU)-specific CD8 T cells from healthy participants...
February 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28159754/reliance-of-wolbachia-on-high-rates-of-host-proteolysis-revealed-by-a-genome-wide-rnai-screen-of-drosophila-cells
#7
Pamela M White, Laura R Serbus, Alain Debec, Adan Codina, Walter Bray, Antoine Guichet, R Scott Lokey, William Sullivan
Wolbachia are gram-negative, obligate, intracellular bacteria carried by a majority of insect species worldwide. Here we use a Wolbachia-infected Drosophila cell line and genome-wide RNAi screening to identify host factors that influence Wolbachia titer. By screening an RNAi library targeting 15,699 transcribed host genes, we identified 36 candidate genes that dramatically reduced Wolbachia titer and 41 that increased Wolbachia titer. Host gene knockdowns that reduced Wolbachia titer spanned a broad array of biological pathways including genes that influenced mitochondrial function and lipid metabolism...
February 3, 2017: Genetics
https://www.readbyqxmd.com/read/28151934/hepatitis-b-virus-modulates-store-operated-calcium-entry-to-enhance-viral-replication-in-primary-hepatocytes
#8
Jessica C Casciano, Nicholas J Duchemin, R Jason Lamontagne, Laura F Steel, Michael J Bouchard
Many viruses modulate calcium (Ca2+) signaling to create a cellular environment that is more permissive to viral replication, but for most viruses that regulate Ca2+ signaling, the mechanism underlying this regulation is not well understood. The hepatitis B virus (HBV) HBx protein modulates cytosolic Ca2+ levels to stimulate HBV replication in some liver cell lines. A chronic HBV infection is associated with life-threatening liver diseases, including hepatocellular carcinoma (HCC), and HBx modulation of cytosolic Ca2+ levels could have an important role in HBV pathogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28150734/mitochondrial-genome-diversity-in-dagger-and-needle-nematodes-nematoda-longidoridae
#9
J E Palomares-Rius, C Cantalapiedra-Navarrete, A Archidona-Yuste, V C Blok, P Castillo
Dagger and needle nematodes included in the family Longidoridae (viz. Longidorus, Paralongidorus, and Xiphinema) are highly polyphagous plant-parasitic nematodes in wild and cultivated plants and some of them are plant-virus vectors (nepovirus). The mitochondrial (mt) genomes of the dagger and needle nematodes, Xiphinema rivesi, Xiphinema pachtaicum, Longidorus vineacola and Paralongidorus litoralis were sequenced in this study. The four circular mt genomes have an estimated size of 12.6, 12.5, 13.5 and 12...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28147362/hochuekkito-a-japanese-herbal-medicine-restores-metabolic-homeostasis-between-mitochondrial-and-glycolytic-pathways-impaired-by-influenza-a-virus-infection
#10
Keita Takanashi, Katsuaki Dan, Sho Kanzaki, Hideki Hasegawa, Kenji Watanabe, Kaoru Ogawa
BACKGROUND: Hochuekkito (HKT), a traditional Japanese herbal medicine (Kampo), has been used to treat symptoms of several diseases. In a recent clinical study, HKT was shown to be protective against the influenza virus infection. However, the underlying mechanism of the prophylactic effect is not clear. Mitochondrial and glycolytic pathways play important roles in cellular energy metabolism to maintain biological functions. These metabolic pathways are affected by the influenza virus infection...
February 2, 2017: Pharmacology
https://www.readbyqxmd.com/read/28143585/molecular-characterization-of-infectious-pancreatic-necrosis-virus-strains-isolated-from-the-three-types-of-salmonids-farmed-in-chile
#11
René A Manríquez, Tamara Vera, Melina V Villalba, Alejandra Mancilla, Vikram N Vakharia, Alejandro J Yañez, Juan G Cárcamo
BACKGROUND: The infectious pancreatic necrosis virus (IPNV) causes significant economic losses in Chilean salmon farming. For effective sanitary management, the IPNV strains present in Chile need to be fully studied, characterized, and constantly updated at the molecular level. METHODS: In this study, 36 Chilean IPNV isolates collected over 6 years (2006-2011) from Salmo salar, Oncorhynchus mykiss, and Oncorhynchus kisutch were genotypically characterized. Salmonid samples were obtained from freshwater, estuary, and seawater sources from central, southern, and the extreme-south of Chile (35° to 53°S)...
January 31, 2017: Virology Journal
https://www.readbyqxmd.com/read/28131843/inhibition-of-drp1-attenuates-mitochondrial-damage-and-myocardial-injury-in-coxsackie-virus-b3-induced-myocarditis
#12
Lin Lin, Ming Zhang, Rui Yan, Hu Shan, Jiayu Diao, Jin Wei
Viral myocarditis (VMC) is closely related to apoptosis, oxidative stress, innate immunity, and energy metabolism, which are all linked to mitochondrial dysfunction. A close nexus between mitochondrial dynamics and cardiovascular disease with mitochondrial dysfunction has been deeply researched, but there is still no relevant report in viral myocarditis. In this study, we aimed to explore the role of Dynamin-related protein 1 (Drp1)-linked mitochondrial fission in VMC. Mice were inoculated with the Coxsackie virus B3 virus (CVB3) and treated with mdivi1 (a Drp1 inhibitor)...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28125040/silymarin-silybin-and-chronic-liver-disease-a-marriage-of-many-years
#13
REVIEW
Alessandro Federico, Marcello Dallio, Carmelina Loguercio
Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation...
January 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28107484/resveratrol-co-treatment-attenuates-the-effects-of-hiv-protease-inhibitors-on-rat-body-weight-and-enhances-cardiac-mitochondrial-respiration
#14
Burger Symington, Rudo F Mapanga, Gavin R Norton, M Faadiel Essop
Since the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months)...
2017: PloS One
https://www.readbyqxmd.com/read/28102850/japanese-encephalitis-virus-induces-human-neural-stem-progenitor-cell-death-by-elevating-grp78-phb-and-hnrnpc-through-er-stress
#15
Sriparna Mukherjee, Noopur Singh, Nabonita Sengupta, Mahar Fatima, Pankaj Seth, Anita Mahadevan, Susarla Krishna Shankar, Arindam Bhattacharyya, Anirban Basu
Japanese encephalitis virus (JEV), which is a causative agent of sporadic encephalitis, harbours itself inside the neural stem/progenitor cells. It is a well-known fact that JEV infects neural stem/progenitor cells and decreases their proliferation capacity. With mass spectrometry-based quantitative proteomic study, it is possible to reveal the impact of virus on the stem cells at protein level. Our aim was to perceive the stem cell proteomic response upon viral challenge. We performed a two-dimensional gel electrophoresis-based proteomic study of the human neural stem cells (hNS1 cell line) post JEV infection and found that 13 proteins were differentially expressed...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28099857/a-systems-approach-reveals-mavs-signaling-in-myeloid-cells-as-critical-for-resistance-to-ebola-virus-in-murine-models-of-infection
#16
Mukta Dutta, Shelly J Robertson, Atsushi Okumura, Dana P Scott, Jean Chang, Jeffrey M Weiss, Gail L Sturdevant, Friederike Feldmann, Elaine Haddock, Abhilash I Chiramel, Sanket S Ponia, Jonathan D Dougherty, Michael G Katze, Angela L Rasmussen, Sonja M Best
The unprecedented 2013-2016 outbreak of Ebola virus (EBOV) resulted in over 11,300 human deaths. Host resistance to RNA viruses requires RIG-I-like receptor (RLR) signaling through the adaptor protein, mitochondrial antiviral signaling protein (MAVS), but the role of RLR-MAVS in orchestrating anti-EBOV responses in vivo is not known. Here we apply a systems approach to MAVS(-/-) mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication through the expression of IFNα, regulation of inflammatory responses in the spleen, and prevention of cell death in the liver, with macrophages implicated as a major cell type influencing host resistance...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28094802/extrinsic-mavs-signaling-is-critical-for-treg-maintenance-of-foxp3-expression-following-acute-flavivirus-infection
#17
Andreia Da Costa, Esteban Garza, Jessica B Graham, Jessica L Swarts, Andrew G Soerens, Michael Gale, Jennifer M Lund
Given the rapid spread of flaviviruses such as West Nile virus (WNV) and Zika virus, it is critical that we develop a complete understanding of the key mediators of an effective anti-viral response. We previously demonstrated that WNV infection of mice deficient in mitochondrial antiviral-signaling protein (MAVS), the signaling adaptor for RNA helicases such as RIG-I, resulted in increased death and dysregulated immunity, which correlated with a failure of Treg expansion following infection. Thus, we sought to determine if intrinsic MAVS signaling is required for participation of Tregs in anti-WNV immunity...
January 17, 2017: Scientific Reports
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
#18
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
#19
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/28076378/p62-pathology-model-in-the-rat-substantia-nigra-with-filamentous-inclusions-and-progressive-neurodegeneration
#20
Kasey L Jackson, Wen-Lang Lin, Sumitra Miriyala, Robert D Dayton, Manikandan Panchatcharam, Kevin J McCarthy, Monica Castanedes-Casey, Dennis W Dickson, Ronald L Klein
One of the proteins most frequently found in neuropathological lesions is the ubiquitin binding protein p62 (sequestosome 1). Post-mortem analysis of p62 is a defining diagnostic marker in several neurodegenerative diseases including amyotrophic lateral sclerosis and inclusion body myositis. Since p62 functions in protein degradation pathways including autophagy, the build-up of p62-positive inclusions suggests defects in protein clearance. p62 was expressed unilaterally in the rat substantia nigra with an adeno-associated virus vector (AAV9) in order to study p62 neuropathology...
2017: PloS One
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