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Liver fibrosis in human immunodeficiency virus/hepatitis c virus coinfection: Diagnostic methods and clinical impact

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World Journal of Hepatology 2015年第24期7卷 2510-2521页

作者： caterina Sagnelli Salvatore Martini Mariantonietta Pisaturo Giuseppe Pasquale Margherita Macera Rosa Zampino Nicola coppola Evangelista Sagnelli Department of Clinical and Experimental Medicine and Surgery "F.Magrassi e A.Lanzara Second University of Naples Department of Mental Health and Public Medicine Section of Infectious DiseasesSecond University of Naples Division of Infectious Diseases AORN Sant’ Anna e San Sebastiano di Caserta Azienda Ospedaliera Universitaria Second University of Naples Department of Medical SurgicalNeurologicalMetabolic and Geriatric SciencesSecond University of Naples

Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis c virus(HcV)-monoinfected and human immunodeficiency virus(HIV)/HcV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HcV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of noninvasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HcVcoinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice.

关键词： Human immunodeficiency virus/hepatitis c virus coi

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Terahertz band communication using plasma wave propagation in multilayer graphene heterostructures

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IET cYBER-PHYSIcAL SYSTEMS: THEORY & APPLIcATIONS 2018年第2期3卷 89-98页

作者： Rakheja, Shaloo NYU Elect & Comp Engn Brooklyn NY 11201 USA

Graphene-based heterostructures provide a viable platform to implement optoelectronic devices that can operate in the terahertz (THz) band. In this study, the authors focus on multilayer (ML) graphene as the building block to implement high-frequency and low-energy plasmonic interconnects for on-chip signalling in next-generation systems. Two specific plasmonic interconnect geometries are analysed: single waveguide (SWG) and parallel-plate waveguide (PPWG). While SWG interconnects support propagating surface plasmons that are polarised in the transverse magnetic direction, in PPWG interconnects, nearly dispersion-less quasi-transverse electromagnetic modes are supported. The dispersion characteristics are derived by solving Maxwell's equations in the device setup in which ML graphene presents an impedance boundary condition. The effects of number of layers, electrostatic screening, and Fermi level are included in the model of intra-band dynamical surface conductivity of ML graphene. The authors also develop analytical models of energy-per-bit and bandwidth density for both SWG and PPWG interconnects. The energy dissipation includes the effect of plasmon generation, detection, and modulation circuitry within a thermal- and shot-noise-limited transmission of information. They quantify optimal interconnect length scales for which plasmonic interconnects provide lower energy and higher bandwidth when compared against their electrical (copper/low-kappa) counterparts at the 2020 ITRS technology node.

关键词： graphene multilayers plasmonics integrated circuit interconnections parallel plate waveguides surface plasmons Maxwell equations Fermi level terahertz band communication plasma wave propagation multilayer graphene heterostructure optoelectronic device ML graphene low-energy plasmonic interconnection geometry analysis on-chip signalling next-generation system single waveguide SWG parallel-plate waveguide PPWG surface plasmon propagation transverse magnetic direction dispersion-less quasitransverse electromagnetic mode Maxwell's equation impedance boundary condition electrostatic screening Fermi level intraband dynamical surface conductivity model plasmon generation effect 2020 ITRS technology node c

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Heat shock reduces HcV replication via regulation of ribosomal L22 in Alu-RNA molecule dependent manner

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Hepatoma Research 2018年第8期4卷 21-30页

作者： Hamada Farghaly Adel A.Guirgis Hany Khalil Department of Molecular Biology Genetic Engineering and Biotechnology Research InstituteUniversity of Sadat CitySadat City 79Egypt

Aim: Hepatitis c virus (HcV) infection is a global health problem that affects more than 180 million people worldwide. HcV is associated with several hepatic and other hepatic disorders including malignancies. HcV is a small enveloped positive-single strand RNA virus that belongs to Hepacivirus in the family Flaviviridae. Here we aim to provide a new therapeutic strategy via treatment of infected HepG2 cells with heat shock (HS). Methods: The potential inhibitory effect of HS on HcV replication was assessed by the relative gene expression of NS5A and its corresponding protein by flowcytometry which has been additionally used to monitor other cellular factors. Results: HS treatment of infected HepG2 cells has the ability to disturb HcV replication possibly via stimulation of the Alu non-coding element which inhibits gene expression of ribosomal L22. Ribosomal protein L22 (RPl22) is one of the abundant RNA-binding proteins that are known to facilitate synthesis and translation of viral RNA and to participate in balancing the protein components of the ribosome itself. conclusion: HS treatment of infected cells leads to up-regulation of long RNA-Alu molecule that regulates the expression of RPL22 and subsequently reduces HcV replication in HepG2 cells.

关键词： Hepatitis c virus Alu non-coding gene heat shock treatment

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The Effect of Water’s cations on the consolidation Settlement Process of clay with Kaolinite

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Materials Today: Proceedings 2018年第1期5卷 214-219页

作者： Soheil Ghareh Sina Kazemian Seyed Vahid Mojtahed Sistani Ali Shayan Mehr Department of Civil Engineering Payame Noor University Tehran I.R. Iran Civil Engineering Islamic Azad University Central Tehran Branch Tehran I.R. Iran

Due to high effect on stability of construction, settlement is very important factor in construction and foundation engineering. Before implementing any project, we should determine the potential of soil in terms of the amount and type of settlement. In saturated clays, water loss from soil performs after a long time (due to low permeability and high water absorption) causes high settlements which are named settlements of consolidations. In this research, experimental study of changes in the initial consolidation settlement process on kaolinite clay (kaolinite) by oedometer test, with the addition of solved cations with concentrations of 50, 150 and 300 Mg/lit (milligrams per liter) in saturated water. Research findings show that application of aluminum (Al +3 ), magnesium (Mg +2 ), calcium (ca +2 ), sodium (Na + ) and potassium (K + ) cations with different concentrations changes the initial consolidation settlement values in appropriation with the concentration and type of cations. The highest reduction in initial consolidation settlement of kaolinite valued at 30.29% related to the sample made with cations magnesium with concentration of 300 Mg/lit.

关键词： c o nsolidation settlement clay Oedometer test Kaolinite

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IL28B SNPs rs12979860 and rs8099917 Are Associated with Inflammatory Response in Argentine chronic HcV Patients

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International Journal of clinical Medicine 2018年第2期9卷 79-91页

作者： Andrés Machicote Diego Flichmann Eloisa Arana Silvia Paz Hugo Fainboim Leonardo Fainboim Pablo M. Fernández Instituto de Inmunología Genética y Metabolismo (INIGEM) Hospital de Clínicas Universidad de Buenos Aires CONICET Buenos Aires Argentina Instituto de Inmunología Genética y Metabolismo (INIGEM) Hospital de Clínicas Universidad de Buenos Aires CONICET Buenos Aires Argentina Cátedra de Virología Facultad de Farmacia y Bioquímica Universidad de Buenos Aires Buenos Aires Argentina Departamento de Inmunología Facultad de Medicina Universidad de Buenos Aires Buenos Aires Argentina Unidad de Hepatología Hospital “Francisco J. Mu&ntilde iz ” Buenos Aires Argentina

Background: Hepatitis c virus (HcV) is a major cause of chronic liver disease, including cirrhosis and liver cancer. The aim of our study was to determine whether IL28B single nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 can be considered a prognostic host factor in untreated chronic HcV patients. Methods: We set up a real-time Allele Specific PcR amplification to determine the allele present in each polymorphic site, and statistically grouped and compared this result with clinical data. Results: We determined rs12979860 and rs8099917 genotype and allele frequencies in a single cohort of untreated chronically HcV-infected patients. We found significant associations between higher inflammatory activity, measured as ALT levels or METAVIR scores and rs12979860 cc (P = 0.0013 and P = 0.0033, respectively) and rs8099917 TT (P = 0.0005 and P = 0.0264, respectively) genotypes. Interestingly, considering both genotypes together, we also found association with ALT levels (P = 0.0003;OR = 5.125) or METAVIR scores (P = 0.0038;OR = 5.179), suggesting and additive effect on liver inflammation in these patients. conclusion: we show association between hepatic inflammatory activity in a single Argentinean untreated chronically HcV cohort and SNPs located in the interferon lambda gene region. The studied polymorphisms, together with further innate and adaptive immune responses, clearly play a role in modulating the HcV infected patients outcome, contributing to hepatic inflammation and possible fibrosis/cirrhosis.

关键词： Hepatic Inflammation Viral Hepatitis chronic Hepatitis c IL28B Latin American Patients

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Predictive factors associated with hepatitis c antiviral therapy response

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World Journal of Hepatology 2015年第12期7卷 1617-1631页

作者： Lourianne Nascimento cavalcante André castro Lyra Hospital Sao Rafael-Gastro-Hepatology Service Department of Medicine Federal University of Bahia

Hepatitis c virus(HcV) infection may lead to significant liver injury, and viral, environmental, host, immunologic and genetic factors may contribute to the differences in the disease expression and treatment response. In the early 2000 s, dual therapy using a combinationof pegylated interferon plus ribavirin(PR) became the standard of care for HcV treatment. In this PR era, predictive factors of therapy response related to virus and host have been identified. In 2010/2011, therapeutic regimens for HcV genotype 1 patients were modified, and the addition of NS3/4a protease inhibitors(boceprevir or telaprevir) to dual therapy increased the effectiveness and chances of sustained virologic response(SVR). Nevertheless, the first-generation triple therapy is associated with many adverse events, some of which are serious and associated with death, particularly in cirrhotic patients. This led to the need to identify viral and host predictive factors that might influence the SVR rate to triple therapy and avoid unnecessary exposure to these drugs. Over the past four years, hepatitis c treatment has been rapidly changing with the development of new therapies and other developments. currently, with the more recent generations of pangenotipic antiviral therapies, there have been higher sustained virologic rates, and prognostic factors may not have the same importance and strength as before. Nonetheless, some variables may still be consistent with the low rates of non-response with regimens that include sofosbuvir, daclatasvir and ledipasvir. In this manuscript, we review the predictive factors of therapy response across the different treatment regimens over the last decade including the new antiviral drugs.

关键词： Hepatitis c Direct acting antivirals Antiviraltherapy Interferon Sustained virologic response

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Dendritic cells: The warriors upfront-turned defunct in chronic hepatitis c infection

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World Journal of Hepatology 2015年第19期7卷 2202-2208页

作者： Meenakshi Sachdeva Yogesh K chawla Sunil K Arora Department of Immuno-pathology Post Graduate Institute of Medical Education and Research Department of Hepatology Post Graduate Institute of Medical Education and Research

Hepatitis c virus(HcV) infection causes tremendousmorbidity and mortality with over 170 million people infected worldwide. HcV gives rise to a sustained, chronic disease in the majority of infected individuals owing to a failure of the host immune system to clear the virus. In general, an adequate immune response is elicited by an efficient antigen presentation by dendritic cells(Dcs), the cells that connect innate and adaptive immune system to generate a specific immune response against a pathogen. However, HcV seems to dysregulate the activity of Dcs, making them less proficient antigen presenting cells for the optimal stimulation of virusspecific T cells, hence interfering with an optimal antiviral immune response. There are discordant reports on the functional status of Dcs in chronic HcV infection(cHc), from no phenotypic or functional defects to abnormal functions of Dcs. Furthermore, the molecular mechanisms behind the impairment of Dc function are even so not completely elucidated during cHc. Understanding the mechanisms of immune dysfunction would help in devising strategies for better management of the disease at the immunological level and help to predict the prognosis of the disease in the patients receiving antiviral therapy. In this review, we have discussed the outcomes of the interaction of Dcs with HcV and the mechanisms of Dc impairment during HcV infection with its adverse effects on the immune response in the infected host.

关键词： Dendritic cells Hepatitis c Mechanism of functiona

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Region-specific irradiation system with heavy-ion microbeam for active individuals of caenorhabditis elegans

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JOURNAL OF RADIATION RESEARcH 2017年第6期58卷 881-886页

作者： Suzuki, Michiyo Hattori, Yuya Sakashita, Tetsuya Yokota, Yuichiro Kobayashi, Yasuhiko Funayama, Tomoo Natl Inst Quantum & Radiol Sci & Technol QST Taka Takasaki Adv Radiat Res Inst Dept Radiat Appl Biol Res 1233 Watanuki Takasaki Gunma 3701292 Japan Tokyo Inst Technol Sch Engn Dept Syst & Control Engn Meguro Ku 2-12-1 Ookayama Tokyo 1528550 Japan

Radiation may affect essential functions and behaviors such as locomotion, feeding, learning and memory. Although whole-body irradiation has been shown to reduce motility in the nematode caenorhabditis elegans, the detailed mechanism responsible for this effect remains unknown. Targeted irradiation of the nerve ring responsible for sensory integration and information processing would allow us to determine whether the reduction of motility following whole-body irradiation reflects effects on the central nervous system or on the muscle cells themselves. We therefore addressed this issue using a collimating microbeam system. However, radiation targeting requires the animal to be immobilized, and previous studies have anesthetized animals to prevent their movement, thus making it impossible to assess their locomotion immediately after irradiation. We developed a method in which the animal was enclosed in a straight, microfluidic channel in a polydimethylsiloxane chip to inhibit free motion during irradiation, thus allowing locomotion to be observed immediately after irradiation. The head region (including the central nervous system), mid region around the intestine and uterus, and tail region were targeted independently. Each region was irradiated with 12 000 carbon ions (c-12;18.3 MeV/u;linear energy transfer = 106.4 keV/mu m), corresponding to 500 Gy at a phi 20 mu m region. Motility was significantly decreased by whole-body irradiation, but not by irradiation of any of the individual regions, including the central nervous system. This suggests that radiation inhibits locomotion by a whole-body mechanism, potentially involving motoneurons and/or body-wall muscle cells, rather than affecting motor control via the central nervous system and the stimulation response.

关键词： region-specific irradiation microbeam carbon ions behavior chip motility c elegans

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Role of inflammatory response in liver diseases: Therapeutic strategies

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World Journal of Hepatology 2018年第1期10卷 1-7页

作者： José A Del campo Paloma Gallego Lourdes Grande Department of Digestive Diseases Valme University Hospital and CIBERehd

Inflammation and tumorigenesis are tightly linked pathways impacting cancer development. Inflammasomes are key signalling platforms that detect pathogenic microorganisms, including hepatitis c virus(HcV) infection, and sterile stressors(oxidative stress, insulin resistance, lipotoxicity) able to activate pro-inflammatory cytokines interleukin-1β and IL-18. Most of the inflammasome complexes that have been described to date contain a NOD-like receptor sensor molecule. Redox state and autophagy can regulate inflammasome complex and, depending on the conditions, can be either pro-or antiapoptotic. Acute and chronic liver diseases are cytokinedriven diseases as several proinflammatory cytokines(IL-1α, IL-1β, tumor necrosis factor-alpha, and IL-6) are critically involved in inflammation, steatosis, fibrosis, and cancer development. NLRP3 inflammasome gain of function aggravates liver disease, resulting in severe liver fibrosis and highlighting this pathway in the pathogenesis of non-alcoholic fatty liver disease. On the other hand, HcV infection is the primary catalyst for progressive liver disease and development of liver cancer. It is well established that HcV-induced IL-1β production by hepatic macrophages plays a critical and central process that promotes liver inflammation and disease. In this review, we aim to clarify the role of the inflammasome in the aggravation of liver disease, and how selective blockade of this main pathway may be a useful strategy to delay fibrosis progression in liver diseases.

关键词： caspase-1 Fibrosis Hepatitis c virus Inflammasome Interleukin-1α Interleukin-1β Liver disease Non-alcoholic fatty liver disease NLRP3 Tumor necrosis factor-alpha

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Extent of natural attenuation of chlorinated ethenes at a contaminated site in Denmark

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Energy Procedia 2018年 146卷 188-193页

作者： Adrian A. Schiefler Dominique J. Tobler Niels D. Overheu Nina Tuxen Capital Region of Denmark Kongens Vænge 2 3400 Hillerød Denmark University of Copenhagen Universitetsparken 5 2100 Copenhagen Denmark

chlorinated solvents contaminated soils and aquifers are a widespread problem in industrialized countries and many require clean-up due to the risk of contaminant flow into groundwater systems. clean-up is costly and often invasive, thus there is high interest in stimulating natural attenuation processes. For this, first an assessment of the type and extent of natural attenuation present at the site is required. Here, we present chemical, isotopic and microbial analyses of waters collected at a chlorinated ethene contaminated site in Denmark to give insights into natural attenuation processes. The data gives indication of complete reductive dechlorination by microbial communities but their extent varies greatly across short distances and between the different geological layers. The data further indicates that overall, chlorinated ethene degradation through natural attenuation is small at this site but near surface degradation due to aerobic co-metabolism or abiotic geochemical reduction could potentially play a role.

关键词： chlorinated solvents remediation compound stable isotope analysis 13 c

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