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https://www.readbyqxmd.com/read/28641051/beneficial-role-of-citrus-fruit-polyphenols-against-hepatic-dysfunctions-a-review
#1
Md Mohabbulla Mohib, Kazi Afnan, Tasfiq Zaman Paran, Salma Khan, Juthika Sarker, Nahid Hasan, Istiaque Hasan, Md Abu Taher Sagor
Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon...
June 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28633455/fetal-metabolic-stress-disrupts-immune-homeostasis-and-induces-pro-inflammatory-responses-in-hiv-1-and-cart-exposed-infants
#2
Johannes C Schoeman, Gontse P Moutloatse, Amy C Harms, Rob J Vreeken, Henriette J Scherpbier, Liesbeth Van Leeuwen, Taco W Kuijpers, Carools J Reinecke, Ruud Berger, Thomas Hankemeier, Madeleine J Bunders
Increased morbidity and fetal growth restriction are reported in uninfected children born to HIV-1-infected women treated with antiretroviral (ARV) therapy. Viruses and/or pharmacological interventions such as ARVs can induce metabolic stress skewing the cell's immune response and restricting (cell) growth. Novel metabolomic techniques provided the opportunity to investigate the impact of fetal HIV-1 and combination ARV therapy (cART)-exposure on the infants' immune-metabolome. Peroxidized lipids, generated by reactive oxygen species, were increased in cART/HIV-1-exposed infants, indicating altered mitochondrial functioning...
June 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28625874/negative-regulation-of-the-rlh-signaling-by-the-e3-ubiquitin-ligase-rnf114
#3
Boren Lin, Qi Ke, Haiying Li, Nichole S Pheifer, David C Velliquette, Douglas W Leaman
The retinoic acid-inducible gene-I (RIG-I)-like helicases (RLH)s are cytoplasmic pattern recognition receptors expressed in both immune and non-immune cells that are essential for detection of intracellular RNA products, primarily of viral origin. Upon binding to viral RNA, RLHs interact with mitochondrial antiviral signaling protein (MAVS) to activate interferon (IFN)-mediated antiviral responses. The RLH/MAVS signaling pathway is regulated by ubiquitination/deubiquitination, in which several ubiquitin-editing proteins play critical roles...
June 15, 2017: Cytokine
https://www.readbyqxmd.com/read/28620346/primary-progressive-multiple-sclerosis-putting-together-the-puzzle
#4
REVIEW
Ahmed Abdelhak, Martin S Weber, Hayrettin Tumani
The focus of multiple sclerosis research has recently turned to the relatively rare and clearly more challenging condition of primary progressive multiple sclerosis (PPMS). Many risk factors such as genetic susceptibility, age, and Epstein-Barr virus (EBV) infection may interdepend on various levels, causing a complex pathophysiological cascade. Variable pathological mechanisms drive disease progression, including inflammation-associated axonal loss, continuous activation of central nervous system resident cells, such as astrocytes and microglia as well as mitochondrial dysfunction and iron accumulation...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28620207/dengue-virus-activates-cgas-through-the-release-of-mitochondrial-dna
#5
Bo Sun, Karin B Sundström, Jun Jie Chew, Pradeep Bist, Esther S Gan, Hwee Cheng Tan, Kenneth C Goh, Tanu Chawla, Choon Kit Tang, Eng Eong Ooi
Cyclic GMP-AMP synthetase (cGAS) is a DNA-specific cytosolic sensor, which detects and initiates host defense responses against microbial DNA. It is thus curious that a recent study identified cGAS as playing important roles in inhibiting positive-sense single-stranded RNA (+ssRNA) viral infection, especially since RNA is not known to activate cGAS. Using a dengue virus serotype 2 (DENV-2) vaccine strain (PDK53), we show that infection creates an endogenous source of cytosolic DNA in infected cells through the release of mitochondrial DNA (mtDNA) to drive the production of cGAMP by cGAS...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28612840/toll-like-receptor-3-in-nasal-cd103-dendritic-cells-is-involved-in-immunoglobulin-a-production
#6
H Takaki, S Kure, H Oshiumi, Y Sakoda, T Suzuki, A Ainai, H Hasegawa, M Matsumoto, T Seya
Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI:C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI:C skews to IgA production in the nasal-associated lymph tissue (NALT) was investigated in mouse models. Nasally instilled polyI:C was endocytosed into CD103(+) dendritic cells (DCs) and induced T-cell activation, including interferon (IFN)-γ production...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28611246/inhibition-of-avian-influenza-a-virus-replication-in-human-cells-by-host-restriction-factor-tufm-is-correlated-with-autophagy
#7
Shu-Ming Kuo, Chi-Jene Chen, Shih-Cheng Chang, Tzu-Jou Liu, Yi-Hsiang Chen, Sheng-Yu Huang, Shin-Ru Shih
Avian influenza A viruses generally do not replicate efficiently in human cells, but substitution of glutamic acid (Glu, E) for lysine (Lys, K) at residue 627 of avian influenza virus polymerase basic protein 2 (PB2) can serve to overcome host restriction and facilitate human infectivity. Although PB2 residue 627 is regarded as a species-specific signature of influenza A viruses, host restriction factors associated with PB2627E have yet to be fully investigated. We conducted immunoprecipitation, followed by differential proteomic analysis, to identify proteins associating with PB2627K (human signature) and PB2627E (avian signature) of influenza A/WSN/1933(H1N1) virus, and the results indicated that Tu elongation factor, mitochondrial (TUFM), had a higher binding affinity for PB2627E than PB2627K in transfected human cells...
June 13, 2017: MBio
https://www.readbyqxmd.com/read/28595015/2-chloro-2-fluoro-ribonucleotide-prodrugs-with-potent-pan-genotypic-activity-against-hepatitis-c-virus-replication-in-culture
#8
Shaoman Zhou, Sawsan Mahmoud, Peng Liu, Longhu Zhou, Maryam Ehteshami, Leda Bassit, Sijia Tao, Robert A Domaoal, Ozkan Sari, Coralie De Schutter, Sheida Amiralaei, Ahmed Khalil, Olivia Ollinger Russell, Tamara R McBrayer, Tony Whitaker, Nageh Abou-Taleb, Franck Amblard, Steven J Coats, Raymond Felix Schinazi
Pan-genotypic nucleoside HCV inhibitors display a high genetic barrier to drug resistance and are the preferred direct acting agents to achieve complete sustained virologic response in humans. Herein, we report, the discovery of a -D-2'-Cl,2'-F-uridine phosphoramidate nucleotide 16, as a non-toxic pan-genotypic anti-HCV agent. Phosphoramidate 16 in its 5'-triphosphate form specifically inhibited HCV NS5B polymerase with no marked inhibition of human polymerases and cellular mitochondrial RNA polymerase. Studies on the intracellular half-life of phosphoramidate 16-TP in live cells demonstrated favorable half-life of 11...
June 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28592532/voltage-dependent-anion-channel-1-interacts-with-ribonucleoprotein-complexes-to-enhance-infectious-bursal-disease-virus-polymerase-activity
#9
Chunyan Han, Xiangwei Zeng, Shuai Yao, Li Gao, Lizhou Zhang, Xiaole Qi, Yulu Duan, Bo Yang, Yulong Gao, Changjun Liu, Yanping Zhang, Yongqiang Wang, Xiaomei Wang
Infectious bursal disease virus (IBDV) is a double-stranded RNA virus. Segment A contains two overlapping open reading frames (ORFs), which encode viral proteins VP2, VP3, VP4, and VP5. Segment B contains one ORF and encodes the viral RNA-dependent RNA polymerase, VP1. IBDV ribonucleoprotein complexes are composed of VP1, VP3, and dsRNA and play a critical role in mediating viral replication and transcription during virus life cycles. Here, we identified a cellular factor, VDAC1, which was upregulated during IBDV infection and found to mediate IBDV polymerase activity...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28587718/%C3%AE-amyloid-precursor-protein-intracellular-domain-controls-mitochondrial-function-by-modulating-phosphatase-and-tensin-homolog-induced-kinase-1-transcription-in-cells-and-in-alzheimer-mice-models
#10
Thomas Goiran, Eric Duplan, Mounia Chami, Alexandre Bourgeois, Wejdane El Manaa, Lila Rouland, Julie Dunys, Inger Lauritzen, Han You, Vuk Stambolic, Maria-Grazia Biféri, Martine Barkats, Sanjay W Pimplikar, Nicolas Sergeant, Morvane Colin, Vanessa A Morais, Raphaelle Pardossi-Piquard, Frédéric Checler, Cristine Alves da Costa
BACKGROUND: Mitophagy and mitochondrial dynamics alterations are two major hallmarks of neurodegenerative diseases. Dysfunctional mitochondria accumulate in Alzheimer's disease-affected brains by yet unexplained mechanisms. METHODS: We combined cell biology, molecular biology, and pharmacological approaches to unravel a novel molecular pathway by which presenilins control phosphatase and tensin homolog-induced kinase 1 (Pink-1) expression and transcription. In vivo approaches were carried out on various transgenic and knockout animals as well as in adeno-associated virus-infected mice...
May 3, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28576489/mitochondrial-protein-p32-hapb1-gc1qr-c1qbp-is-required-for-efficient-respiratory-syncytial-virus-production
#11
MengJie Hu, Hong-Mei Li, Marie A Bogoyevitch, David A Jans
Respiratory syncytial virus (RSV) is a major cause of respiratory infections in infants and the elderly, leading to more deaths than influenza each year, but there is no antiviral or efficacious vaccine currently available. Here we examine the role in infection of the host mitochondrial protein p32 (HABP/gC1qR/C1qbp) for the first time. RSV replication as well as infectious virus production was significantly reduced by p32 siRNA knockdown, consistent with an important role for p32 in RSV infection. p32 showed distinct mitochondrial localization throughout RSV infection, but immunostaining and high resolution confocal imaging for p32 as well as MitoTracker Red and cytochrome c, revealed clear changes in mitochondrial organization in RSV infection, with perinuclear mitochondrial compaction and asymmetric distribution at 8 and 18 h post-infection, respectively...
May 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28570836/the-influence-of-hepatitis-c-virus-therapy-on-the-dna-base-excision-repair-system-of-peripheral-blood-mononuclear-cells
#12
Piotr Czarny, Anna Merecz-Sadowska, Kinga Majchrzak, Maciej Jabłkowski, Janusz Szemraj, Tomasz Śliwiński, Bolesław Karwowski
Hepatitis C virus (HCV) can infect extrahepatic tissues, including lymphocytes, creating reservoir of the virus. Moreover, HCV proteins can interact with DNA damage response proteins of infected cells. In this article we investigated the influence of the virus infection and a new ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) anti-HCV therapy on the PBMCs (peripheral blood mononuclear cells, mainly lymphocytes) DNA base excision repair (BER) system. BER protein activity was analyzed in the nuclear and mitochondrial extracts (NE and ME) of PBMC isolated from patients before and after therapy, and from subjects without HCV, using modeled double-strand DNA, with 2'-deoxyuridine substitution as the DNA damage...
June 1, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28566380/seneca-valley-virus-suppresses-host-type-i-interferon-production-by-targeting-adaptor-proteins-mavs-trif-and-tank-for-cleavage
#13
Suhong Qian, Wenchun Fan, Tingting Liu, Mengge Wu, Huawei Zhang, Xiaofang Cui, Yun Zhou, Junjie Hu, Shaozhong Wei, Huanchun Chen, Xiangmin Li, Ping Qian
Seneca Valley Virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anti-cancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial anti-viral signaling (MAVS), Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF), and TRAF family member-associated NF-κB activator (TANK) via viral 3C(pro) SVV 3C(pro) mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28560395/hsvtk-gcv-system-on-hepatoma-carcinoma-cells-construction-of-the-plasmid-pcdna3-1%C3%A2-pafp-tk-and-targeted-killing-effect
#14
Yong-Fang Li, Yang-Yang Yuan, Ying-Min Zhang, Na Zhao, Qi Zhang, Fan-Xiu Meng, Ran-Peng Gao, Bao-Feng Yu, Yue-Hong Zhang, Rui Guo, Hai-Long Wang, Jun Xie, Jun Xu, Qin Qin, Xiu-Shan Dong
Previous studies demonstrated that herpes simplex virus thymidine kinase (HSVtk) could phosphorylate non‑toxic gancyclovir (GCV) efficiently to produce phosphorylated products that result in cell apoptosis, to kill tumor cells. The present study aimed to construct a plasmid vector, pcDNA3.1‑pAFP‑TK, carrying the suicide gene driven by the alpha‑fetoprotein (AFP) promoter, to investigate the cytotoxicity of HSVtk/GCV suicide gene system on hepatoma carcinoma cells. Reverse transcription‑polymerase chain reaction and western blotting results demonstrated that the HSVtk gene was effectively expressed in HepG2 hepatoma carcinoma cells transfected with pcDNA3...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28559425/fgf21-ameliorates-diabetic-cardiomyopathy-by-activating-the-ampk-paraoxonase-1-signaling-axis-in-mice
#15
Fan Wu, Baile Wang, Saisai Zhang, Lihua Shi, Yanfang Wang, Rongrong Xiong, Xuebo Pan, Fanghua Gong, Xiaokun Li, Zhuofeng Lin
Aims: The aim in present study is to explore the molecular mechanism of FGF21 against diabetic cardiomyopathy. Materials and methods: FGF21 deficient mice and wild type littermates were used to induce diabetic mice by treatment with streptozotocin/high-fat diet (STZ/HFD), and then evaluated the difference of diabetic cardiomyopathy between two types of mice. Otherwise, primary cultured cardiomyocytes were also used to explore the potential molecular mechanism of FGF21 against high glucose-induced cardiomyocyte injuries...
May 30, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28559295/polyvalent-proteins-a-pervasive-theme-in-the-inter-genomic-biological-conflicts-of-bacteriophages-and-conjugative-elements
#16
Lakshminarayan M Iyer, A Maxwell Burroughs, Swadha Anand, Robson F de Souza, L Aravind
Intense biological conflicts between prokaryotic genomes and their genomic parasites have resulted in an arms-race in terms of the molecular "weaponry" deployed on both sides. Using a recursive computational approach we uncovered a remarkable class of multidomain proteins with 2-15 domains in the same polypeptide deployed by viruses and plasmids in such conflicts. Domain architectures and genomic contexts indicate that they are part of a widespread conflict strategy involving proteins injected into the host cell along with parasite DNA during the earliest phase of infection...
May 30, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28559253/nucleotide-substrate-specificity-of-hepatitis-c-analogs-for-human-mitochondrial-rna-polymerase
#17
Maryam Ehteshami, Longhu Zhou, Sheida Amiralaei, Jadd R Shelton, Jong Hyun Cho, Hongwang Zhang, Hao Li, Xiao Lu, Tugba Ozturk, Richard Stanton, Franck Amblard, Tamara R McBrayer, Steven J Coats, Raymond F Schinazi
Nucleoside analog inhibitors (NAI) are an important class of antiviral agents. Although highly effective, some NAI with anti-hepatitis C virus (HCV) activity can cause toxicity presumably due to off-target inhibition of host mitochondrial RNA polymerase (POLRMT). The in vitro nucleotide substrate specificity of POLRMT enzyme was studied in order to explore structure-activity relationships that can facilitate the identification of non-toxic NAI. These finding have important implications for all anti-RNA virus NAI development...
May 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28558073/hepatitis-e-virus-persists-in-the-presence-of-a-type-iii-interferon-response
#18
Xin Yin, Xinlei Li, Charuta Ambardekar, Zhimin Hu, Sébastien Lhomme, Zongdi Feng
The RIG-I-like RNA helicase (RLR)-mediated interferon (IFN) response plays a pivotal role in the hepatic antiviral immunity. The hepatitis A virus (HAV) and the hepatitis C virus (HCV) counter this response by encoding a viral protease that cleaves the mitochondria antiviral signaling protein (MAVS), a common signaling adaptor for RLRs. However, a third hepatotropic RNA virus, the hepatitis E virus (HEV), does not appear to encode a functional protease yet persists in infected cells. We investigated HEV-induced IFN responses in human hepatoma cells and primary human hepatocytes...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28554653/dendritic-cells-during-mousepox-the-role-of-delayed-apoptosis-in-the-pathogenesis-of-infection
#19
Piotr Orlowski, Maja Pardecka, Joanna Cymerys, Malgorzata Krzyzowska
Dendritic cells (DCs) are effector cells linking the innate immune system with the adaptive immune response. Many viruses eliminate DCs to prevent host response, induce immunosuppression and to maintain chronic infection. In this study, we examined apoptotic response of dendritic cells during in vitro and in vivo infection with ectromelia virus (ECTV), the causative agent of mousepox. ECTV-infected bone marrow dendritic cells (BMDCs) from BALB/c mice underwent apoptosis through mitochondrial pathway at 48 h post infection, up-regulated FasL and decreased expression of anti-apoptotic Bcl-2 and pro-apoptotic Fas...
May 26, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28532532/global-phylogenetic-relationships-population-structure-and-gene-flow-estimation-of-trialeurodes-vaporariorum-greenhouse-whitefly
#20
J M Wainaina, P De Barro, L Kubatko, M A Kehoe, J Harvey, D Karanja, L M Boykin
Trialeurodes vaporariorum (Westwood, 1856) (Greenhouse whitefly) is an agricultural pest of global importance. It is associated with damage to plants during feeding and subsequent virus transmission. Yet, global phylogenetic relationships, population structure, and estimation of the rates of gene flow within this whitefly species remain largely unexplored. In this study, we obtained and filtered 227 GenBank records of mitochondrial cytochrome c oxidase I (mtCOI) sequences of T. vaporariorum, across various global locations to obtain a final set of 217 GenBank records...
May 23, 2017: Bulletin of Entomological Research
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