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https://www.readbyqxmd.com/read/29036837/simvastatin-as-a-potential-disease-modifying-therapy-for-patients-with-parkinson-s-disease-rationale-for%C3%A2-clinical-trial-and-current-progress
#1
Camille B Carroll, Richard K H Wyse
Many now believe the holy grail for the next stage of therapeutic advance surrounds the development of disease-modifying approaches aimed at intercepting the year-on-year neurodegenerative decline experienced by most patients with Parkinson's disease (PD). Based on recommendations of an international committee of experts who are currently bringing multiple, potentially disease-modifying, PD therapeutics into long-term neuroprotective PD trials, a clinical trial involving 198 patients is underway to determine whether Simvastatin provides protection against chronic neurodegeneration...
October 13, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/29034492/transcriptome-analyses-reveal-genes-and-pathways-associated-with-fatty-acid-composition-traits-in-pigs
#2
J Zhang, L Cui, J Ma, C Chen, B Yang, L Huang
Fatty acid composition is associated with meat quality in pigs as well as with obesity- and diabetes-related traits in humans. Liver and muscle are important tissues for fatty acid metabolism. In this study, we evaluated correlations between liver and muscle transcriptomes and fatty acid composition traits in muscle and abdominal fat tissues in 335 F2 pigs from a White Duroc × Erhualian F2 pig resource population. Transcripts significantly correlated with fatty acid composition traits were enriched for genes involved in the categories of triglyceride catabolic process, mitochondrial function, hematological and immune system, and disease such as Type II diabetes...
October 16, 2017: Animal Genetics
https://www.readbyqxmd.com/read/29034472/protective-effects-of-curcumin-against-aflatoxicosis-a-comprehensive-review
#3
REVIEW
Mohammad Mohajeri, Behzad Behnam, Arrigo F G Cicero, Amirhossein Sahebkar
Aflatoxicosis is a deleterious medical condition that results from aflatoxins (AFs) or ochratoxins (OTs). Contamination with these toxins exerts detrimental effects on the liver, kidneys, reproductive organs, and also on immunological and cardiovascular systems. Aflatoxicosis is closely associated with overproduction of reactive oxygen species (ROS) as key contributors to oxidative and nitrosative stress responses, and subsequent damages to lipids, proteins, RNA, and DNA. The main target organ for AF toxicity is the liver, where DNA adducts, degranulation of endoplasmic reticulum, increased hepatic lipid peroxide, GSH depletion, mitochondrial dysfunction, and reduction of enzymatic and non-enzymatic antioxidants are manifestations of aflatoxicosis...
October 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29032101/mitochondrial-activity-in-t-cells
#4
REVIEW
Gabriela Desdín-Micó, Gonzalo Soto-Heredero, María Mittelbrunn
Mitochondria fulfill important and diverse roles during the different stages of T cell adaptive responses. Here we discuss the role of the mitochondria in T cells from the initial steps of activation at the immune synapse to their participation in memory responses and T cell exhaustion. Mitochondria are relocated to the immune synapse in order to supply local ATP and to aid calcium signaling. During expansion and proliferation, mitochondrial reactive oxygen species drive proliferation. Aerobic glycolysis, glutaminolysis and fatty acid oxidation regulate the program of differentiation into effector or regulatory T cell subsets, and mitochondrial remodeling proteins are required for the long-lasting phenotype of memory cells...
October 12, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29029603/the-pathophysiological-role-of-mitochondrial-oxidative-stress-in-lung-diseases
#5
REVIEW
Xiaojing Liu, Zhihong Chen
Mitochondria are critically involved in reactive oxygen species (ROS)-dependent lung diseases, such as lung fibrosis, asbestos, chronic airway diseases and lung cancer. Mitochondrial DNA (mtDNA) encodes mitochondrial proteins and is more sensitive to oxidants than nuclear DNA. Damage to mtDNA causes mitochondrial dysfunction, including electron transport chain impairment and mitochondrial membrane potential loss. Furthermore, damaged mtDNA also acts as a damage-associated molecular pattern (DAMP) that drives inflammatory and immune responses...
October 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29029400/rat-embryonic-fibroblasts-immortalized-by-mrps18-2-protein-are-target-for-nk-cells
#6
Muhammad Mushtaq, Pradeepa N Pangigadde, Suhas Darekar, Erik Dissen, Elena Kashuba
Overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts (REFs). The derived cells (18IM) expressed embryonic stem cell markers. Noteworthy, genes encoding the COX family proteins were up-regulated significantly. It is known that the COX family proteins are involved in the regulation of immune response. In the present work we demonstrate that 18IM cells behave like stem cells when subjected to directed differentiation in vitro. However, unlike stem cells, 18IM cells do not develop tumors in vivo, in SCID mice...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029277/mir-122-release-in-exosomes-precedes-overt-tolvaptan-induced-necrosis-in-a-primary-human-hepatocyte-micropatterned-coculture-model
#7
Merrie Mosedale, J Scott Eaddy, O Joseph Trask, Natalie S Holman, Kristina K Wolf, Edward LeCluyse, Brenton R Ware, Salman R Khetani, Jingtao Lu, William J Brock, Sharin E Roth, Paul B Watkins
Idiosyncratic drug-induced liver injury (IDILI) is thought to often result from an adaptive immune attack on the liver. However, it has been proposed that the cascade of events culminating in an adaptive immune response begins with drug-induced hepatocyte stress, release of exosomal danger signals, and innate immune activation, all of which may occur in the absence of significant hepatocelluar death. A micropatterned coculture model (HepatoPac®) was used to explore the possibility that changes in exosome content precede overt necrosis in response to the IDILI drug tolvaptan...
September 28, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29028836/affected-pathways-and-transcriptional-regulators-in-gene-expression-response-to-an-ultra-marathon-trail-global-and-independent-activity-approaches
#8
Maria Maqueda, Emma Roca, Daniel Brotons, Jose Manuel Soria, Alexandre Perera
Gene expression (GE) analyses on blood samples from marathon and half-marathon runners have reported significant impacts on the immune and inflammatory systems. An ultra-marathon trail (UMT) represents a greater effort due to its more testing conditions. For the first time, we report the genome-wide GE profiling in a group of 16 runners participating in an 82 km UMT competition. We quantified their differential GE profile before and after the race using HuGene2.0st microarrays (Affymetrix Inc., California, US)...
2017: PloS One
https://www.readbyqxmd.com/read/29027916/a-next-generation-sequencing-approach-uncovers-viral-transcripts-incorporated-in-poxvirus-virions
#9
Marica Grossegesse, Joerg Doellinger, Berit Haldemann, Lars Schaade, Andreas Nitsche
Transcripts are known to be incorporated in particles of DNA viruses belonging to the families of Herpesviridae and Mimiviridae, but the presence of transcripts in other DNA viruses, such as poxviruses, has not been analyzed yet. Therefore, we first established a next-generation-sequencing (NGS)-based protocol, enabling the unbiased identification of transcripts in virus particles. Subsequently, we applied our protocol to analyze RNA in an emerging zoonotic member of the Poxviridae family, namely Cowpox virus...
October 13, 2017: Viruses
https://www.readbyqxmd.com/read/29027371/differential-proteomic-analysis-of-dimethylnitrosamine-dmn-induced-liver-fibrosis
#10
Xiujie Liu, Rongji Dai, Ming Ke, Imran Suheryani, Weiwei Meng, Yulin Deng
Liver fibrosis is a common pathological feature of many chronic liver diseases. To characterize the entire panorama of proteome changes in DMN-induced liver fibrosis, iTRAQ-based differential proteomic analysis was performed with DMN-induced liver fibrosis rats. A total of 4155 confidently identified proteins were found, with 365 proteins showing significant changes (fold changes of >1.5 or < 0.67, P < 0.05). In metabolic activation, proteins assigned to drug metabolism enzymes (e.g., CYP2D1) changed, suggesting that the liver protection mechanism was activated to relieve DMN toxicity...
October 13, 2017: Proteomics
https://www.readbyqxmd.com/read/29024797/nlrx1-modulates-differentially-nlrp3-inflammasome-activation-and-nf-%C3%AE%C2%BAb-signaling-during-fusobacterium-nucleatum-infection
#11
Shu-Chen Hung, Pei-Rong Huang, Cássio Luiz Coutinho Almeida-da-Silva, Kalina R Atanasova, Ozlem Yilmaz, David M Ojcius
NOD-like receptors (NLRs) play a large role in regulation of host innate immunity, yet their role in periodontitis remains to be defined. NLRX1, a member of the NLR family that localizes to mitochondria, enhances mitochondrial ROS (mROS) generation. mROS can activate the NLRP3 inflammasome, yet the role of NLRX1 in NLRP3 inflammasome activation has not been examined. In this study, we revealed the mechanism by which NLRX1 positively regulates ATP-induced NLRP3 inflammasome activation through mROS in gingival epithelial cells (GECs)...
October 9, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29024780/toxicogenomics-of-the-flame-retardant-tris-2-butoxyethyl-phosphate-in-hepg2-cells-using-rna-seq
#12
Boris V Krivoshiev, Gerrit T S Beemster, Katrien Sprangers, Bart Cuypers, Kris Laukens, Ronny Blust, Steven J Husson
Tris (2-butoxyethyl) phosphate (TBOEP) is a compound produced at high volume that is used as both a flame retardant and a plasticizer. It is persistent and bioaccumulative, yet little is known of its toxicological modes of action. Such insight may aid risk assessment in a weight-of-evidence approach supplementing current testing strategies. We used an RNA sequencing approach as an unbiased and sensitive tool to explore potential negative health effects of sub-cytotoxic concentrations of TBOEP on the transcriptome of the human liver hepatocellular carcinoma cell line, HepG2, with the lowest concentration used potentially holding relevance to human physiological levels...
October 9, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29018447/trim25-in-the-regulation-of-the-antiviral-innate-immunity
#13
REVIEW
María Martín-Vicente, Luz M Medrano, Salvador Resino, Adolfo García-Sastre, Isidoro Martínez
TRIM25 is an E3 ubiquitin ligase enzyme that is involved in various cellular processes, including regulation of the innate immune response against viruses. TRIM25-mediated ubiquitination of the cytosolic pattern recognition receptor RIG-I is an essential step for initiation of the intracellular antiviral response and has been thoroughly documented. In recent years, however, additional roles of TRIM25 in early innate immunity are emerging, including negative regulation of RIG-I, activation of the melanoma differentiation-associated protein 5-mitochondrial antiviral signaling protein-TRAF6 antiviral axis and modulation of p53 levels and activity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28992604/photodynamic-effects-on-fonsecaea-monophora-conidia-and-raw264-7-in-vitro
#14
Xiuwen Yi, Cindy Fransisca, Ya He, Yinghui Liu, Sha Lu, Liya He, Liyan Xi
Chromoblastomycosis (CBM), one of the neglected tropical diseases, is hard to cure and easy to be recurrent. Many studies suggest that macrophage is involved in the pathogenesis of chromoblastomycosis and the fungicidal effect of 5-Aminolaevulinic Acid-Based Photodynamic Therapy (ALA-PDT) against F. monophora (one of the main causative agent of chromoblastomycosis) has shown great promise. However, the fungicidal ability of ALA-PDT to F. monophora is still controversial and the molecular mechanism and immune mechanism of ALA-PDT against F...
September 18, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28992511/plant-mitochondrial-membranes-adding-structure-and-new-functions-to-respiratory-physiology
#15
REVIEW
Markus Schwarzländer, Philippe Fuchs
The membranes of mitochondria are focal points of cellular physiology and respiratory energy transformation. Recent discoveries have started painting a refined picture of plant mitochondrial membranes as platforms in which structure and function have evolved in an interconnected and dynamically regulated manner. Hosting ancillary functions that interact with other mitochondrial properties gives mitochondria the characteristics of multitasking and integrated molecular mega machines. We review recent insights into the makeup and the plasticity of the outer and inner mitochondrial membranes, their intimate relationship with respiratory function and regulation, and their properties in mediating solute transport...
October 6, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28991908/mitochondrial-dual-coding-genes-in-trypanosome-brucei
#16
Laura E Kirby, Donna Koslowsky
Trypanosoma brucei is transmitted between mammalian hosts by the tsetse fly. In the mammal, they are exclusively extracellular, continuously replicating within the bloodstream. During this stage, the mitochondrion lacks a functional electron transport chain (ETC). Successful transition to the fly, requires activation of the ETC and ATP synthesis via oxidative phosphorylation. This life cycle leads to a major problem: in the bloodstream, the mitochondrial genes are not under selection and are subject to genetic drift that endangers their integrity...
October 9, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28988824/citrobacter-rodentium-subverts-atp-flux-and-cholesterol-homeostasis-in-intestinal-epithelial-cells-in%C3%A2-vivo
#17
Cedric N Berger, Valerie F Crepin, Theodoros I Roumeliotis, James C Wright, Danielle Carson, Meirav Pevsner-Fischer, R Christopher D Furniss, Gordon Dougan, Mally Bachash, Lu Yu, Abigail Clements, James W Collins, Eran Elinav, Gerald J Larrouy-Maumus, Jyoti S Choudhary, Gad Frankel
The intestinal epithelial cells (IECs) that line the gut form a robust line of defense against ingested pathogens. We investigated the impact of infection with the enteric pathogen Citrobacter rodentium on mouse IEC metabolism using global proteomic and targeted metabolomics and lipidomics. The major signatures of the infection were upregulation of the sugar transporter Sglt4, aerobic glycolysis, and production of phosphocreatine, which mobilizes cytosolic energy. In contrast, biogenesis of mitochondrial cardiolipins, essential for ATP production, was inhibited, which coincided with increased levels of mucosal O2 and a reduction in colon-associated anaerobic commensals...
October 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28987733/how-inflammasomes-inform-adaptive-immunity
#18
REVIEW
Charles Evavold, Jonathan C Kagan
An immune response consists of a finely orchestrated interplay between initial recognition of potential microbial threats by the innate immune system and subsequent licensed adaptive immune neutralization. The initial recognition integrates environmental cues derived from pathogen associated molecular patterns (PAMPs) and cell intrinsic damage associated molecular patterns (DAMPs) to contextualize the insult and inform a tailored adaptive response via T and B lymphocytes. While there is much data to support the role of transcriptional responses downstream of pattern recognition receptors (PRRs) in informing the adaptive immune response, markedly less attention has been paid to the role of post-translational responses to PAMP and DAMP recognition by the innate immune system, and how this may influence adaptive immunity...
October 5, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28986577/replication-defective-viral-genomes-exploit-a-cellular-pro-survival-mechanism-to-establish-paramyxovirus-persistence
#19
Jie Xu, Yan Sun, Yize Li, Gordon Ruthel, Susan R Weiss, Arjun Raj, Daniel Beiting, Carolina B López
Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many RNA virus infections. However, DVGs can also facilitate viral persistence. Why and how these two opposing functions of DVGs are achieved remain unknown. Here we report that during Sendai and respiratory syncytial virus infections DVGs selectively protect a subpopulation of cells from death, thereby promoting the establishment of persistent infections. We find that during Sendai virus infection this phenotype results from DVGs stimulating a mitochondrial antiviral-signaling (MAVS)-mediated TNF response that drives apoptosis of highly infected cells while extending the survival of cells enriched in DVGs...
October 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28986259/inhibition-of-constitutive-nf-%C3%AE%C2%BAb-activity-induces-platelet-apoptosis-via-er-stress
#20
Manoj Paul, Kempaiah Kemparaju, Kesturu S Girish
Platelets are anucleate cells, known for their pivotal roles in hemostasis, inflammation, immunity, and disease progression. Being anuclear, platelets are known to express several transcriptional factors which exert nongenomic functions, including the positive and negative regulation of platelet activation. NF-κB is one such transcriptional factor involved in the regulation of genes for survival, proliferation, inflammation and immunity. Although, the role NF-κB in platelet activation and aggregation is partially known, its function in management of platelet survival and apoptosis remain unexplored...
October 4, 2017: Biochemical and Biophysical Research Communications
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