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https://www.readbyqxmd.com/read/28820612/the-potential-of-signal-peptide-peptidase-as-a-therapeutic-target-for-hepatitis-c
#1
Kohji Moriishi
Chronic infection with hepatitis C virus (HCV) causes liver steatosis, cirrhosis, metabolic syndrome with inflammation, and eventually leads to hepatocellular carcinoma. HCV core protein is a well-known capsid protein and pathogenic factor related to lipid accumulation, type 2 diabetes mellitus, and carcinogenesis. Cleavage of the C-terminal transmembrane region by signal peptide peptidase (SPP) is required for maturation of the core protein. Areas covered: Herein, this review details the general aspects of the structure, lifecycle, pathogenesis, and maturation of the HCV core protein, the function of SPP, and clinically available direct-acting antivirals (DAAs)...
August 18, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28820498/interference-of-apoptosis-by-hepatitis-b-virus
#2
REVIEW
Shaoli Lin, Yan-Jin Zhang
Hepatitis B virus (HBV) causes liver diseases that have been a consistent problem for human health, leading to more than one million deaths every year worldwide. A large proportion of hepatocellular carcinoma (HCC) cases across the world are closely associated with chronic HBV infection. Apoptosis is a programmed cell death and is frequently altered in cancer development. HBV infection interferes with the apoptosis signaling to promote HCC progression and viral proliferation. The HBV-mediated alteration of apoptosis is achieved via interference with cellular signaling pathways and regulation of epigenetics...
August 18, 2017: Viruses
https://www.readbyqxmd.com/read/28819247/delta-inulin-based-adjuvants-promote-the-generation-of-polyfunctional-cd4-t-cell-responses-and-protection-against-mycobacterium-tuberculosis-infection
#3
Claudio Counoupas, Rachel Pinto, Gayathri Nagalingam, Warwick J Britton, Nikolai Petrovsky, James A Triccas
There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818246/cancer-prevention-during-early-adulthood-highlights-from-a-meeting-of-experts
#4
Dawn M Holman, Mary C White, Meredith L Shoemaker, Greta M Massetti, Mary C Puckett, Claire D Brindis
Using a life course approach, the Centers for Disease Control and Prevention's Division of Cancer Prevention and Control and the National Association of Chronic Disease Directors co-hosted a 2-day meeting with 15 multidisciplinary experts to consider evidence linking factors in early adulthood to subsequent cancer risk and strategies for putting that evidence into practice to reduce cancer incidence. This paper provides an overview of key themes from those meeting discussions, drawing attention to the influence that early adulthood can have on lifetime cancer risk and potential strategies for intervention during this phase of life...
September 2017: American Journal of Preventive Medicine
https://www.readbyqxmd.com/read/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#5
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28816347/the-silent-enemy-celiac-disease-goes-viral
#6
Alberto Reale, Marta Trevisan, Gualtiero Alvisi, Giorgio Palù
Celiac disease is a multifactorial autoimmune chronic inflammatory disorder affecting approximately one percent of the worldwide population. In such patients, ingestion of gluten proteins from cereals like wheat, barley and rye causes damage of the small intestine mucosa, with potentially severe consequences. Onset of the disease in predisposed individuals is believed to require a still not clearly identified external trigger, such as viral infections. A very recent study has begun to shed light on a possible mechanistic basis for this hypothesis, and surprisingly linked intestinal infections caused by common reoviruses to the onset of celiac disease...
August 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28815344/long-term-survival-after-hematopoietic-stem-cell-transplantation-for-complete-stat1-deficiency
#7
Samuele Naviglio, Elena Soncini, Donatella Vairo, Arnalda Lanfranchi, Raffaele Badolato, Fulvio Porta
PURPOSE: Complete signal transducer and activator of transcription 1 (STAT1) deficiency is a rare autosomal recessive condition characterized by impairment of intracellular signaling from both type I and type II interferons (IFN). Affected patients are prone to early severe mycobacterial and viral infections, which usually result in death before 18 months of age. We previously reported a patient affected by complete STAT1 deficiency who underwent hematopoietic stem cell transplantation (HSCT)...
August 16, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28815225/chronic-in-vivo-interaction-of-dendritic-cells-expressing-the-ligand-rae-1%C3%AE%C2%B5-with-nk-cells-impacts-nkg2d-expression-and-function
#8
Maelig G Morvan, Marine Champsaur, Boris Reizis, Lewis L Lanier
To investigate how dendritic cells (DCs) interact with NK cells in vivo, we developed a novel mouse model in which Rae-1ε, a ligand of the NKG2D receptor, is expressed in cells with high levels of CD11c. In these CD11c-Rae1 mice, expression of Rae-1 was confirmed on all subsets of DCs and a small subset of B and T cells, but not on NK cells. DC numbers and activation status were unchanged, and NK cells in these CD11c-Rae1 mice presented the same Ly49 repertoire and maturation levels as their littermate wildtype controls...
May 1, 2017: Immunohorizons
https://www.readbyqxmd.com/read/28814517/zinc-salts-block-hepatitis-e-virus-replication-by-inhibiting-the-activity-of-viral-rna-dependent-rna-polymerase
#9
Nidhi Kaushik, Chandru Subramani, Saumya Anang, Rajagopalan Muthumohan, Shalimar, Baibaswata Nayak, C T Ranjith-Kumar, Milan Surjit
Hepatitis E virus (HEV) causes an acute, self limiting hepatitis in normal individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going upto 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource starved countries. No specific anti-viral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28811492/interferon-alpha-treatment-rapidly-clears-hepatitis-e-virus-infection-in-humanized-mice
#10
Martijn D B van de Garde, Suzan D Pas, Gertine W van Oord, Lucio Gama, Youkyung Choi, Robert A de Man, Andre Boonstra, Thomas Vanwolleghem
Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810829/blocking-il-10-signalling-at-the-time-of-immunization-does-not-increase-unwanted-side-effects-in-mice
#11
Guoying Ni, Zaowen Liao, Shu Chen, Tianfang Wang, Jianwei Yuan, Xuan Pan, Kate Mounsey, Shelley Cavezza, Xiaosong Liu, Ming Q Wei
BACKGROUND: Cancer therapeutic vaccine induced cytotoxic T cell (CTL) responses are pivotal for the killing of tumour cells. Blocking interleukin 10 (IL-10) signalling at the time of immunization increases vaccine induced CTL responses and improves prevention of tumour growth in animal models compared to immunization without an IL-10 signalling blockade. Therefore, this immunization strategy may have potential to curtail cancer in a clinical setting. However, IL-10 deficiency leads to autoimmune disease in the gut...
August 15, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28807812/evaluation-and-clinical-validation-of-two-field-deployable-reverse-transcription-insulated-isothermal-pcr-assays-for-the-detection-of-the-middle-east-respiratory-syndrome-coronavirus
#12
Yun Young Go, Yeon-Sook Kim, Shinhye Cheon, Sangwoo Nam, Keun Bon Ku, Meehyein Kim, Nam Hyuk Cho, Hyun Park, Pei-Yu Alison Lee, Yu-Chun Lin, Yun-Long Tsai, Hwa-Tang Thomas Wang, Udeni B R Balasuriya
Middle East respiratory syndrome (MERS) is an emerging zoonotic viral respiratory disease that was first identified in Saudi Arabia in 2012. In 2015, the largest MERS outbreak outside of the Middle East region occurred in the Republic of Korea. The rapid nosocomial transmission of MERS-coronavirus (MERS-CoV) in Korean healthcare settings highlighted the importance and urgent need for a rapid and reliable on-site diagnostic assay to implement effective control and preventive measures. Here, we describe the evaluation and validation of two newly developed reverse transcription-insulated isothermal PCR (RT-iiPCR) methods targeting the ORF1a and upE genes of MERS-CoV...
August 11, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28807557/the-role-of-toll-like-receptor-3-in-chronic-contact-hypersensitivity-induced-by-repeated-elicitation
#13
Risa Yasuike, Risa Tamagawa-Mineoka, Mayumi Ueta, Naomi Nakamura, Shigeru Kinoshita, Norito Katoh
BACKGROUND: Accumulating evidence suggests that Toll-like receptor (TLR)-3 signaling is involved in non-infectious immune and inflammatory reactions as well as in viral infections. The skin of patients with atopic dermatitis (AD) is often infected with virus and bacteria, leading to the aggravation of atopic symptoms. These findings suggest TLR3 signaling may be involved in the pathogenesis of AD, but the exact role of TLR3 in AD remains to be defined. OBJECTIVE: The purpose of this study was to investigate the role of TLR3 in chronic contact hypersensitivity reactions induced by repeated elicitation, resembling the features of AD...
August 4, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28801807/hyaluronan-mediated-mononuclear-leukocyte-binding-to-gingival-fibroblasts
#14
Daniel Hagenfeld, Nico T Mutters, Inga Harks, Raphael Koch, Ti-Sun Kim, Peter Prehm
OBJECTIVES: Binding of mononuclear leukocytes to hyaluronan cable structures is a well-known pathomechanism in several chronic inflammatory diseases, but has not yet described for chronic oral inflammations. The aim of this study was to evaluate if and how binding of mononuclear leukocytes to pathologic hyaluronan cable structures can be induced in human gingival fibroblasts. MATERIAL AND METHODS: Experiments were performed with human gingival fibroblasts and peripheral blood mononuclear cells (PBMCs) from three healthy blood donors...
August 12, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28800954/a-tim-3-oligonucleotide-aptamer-enhances-t-cell-functions-and-potentiates-tumor-immunity-in-mice
#15
Tal Gefen, Iris Castro, Darija Muharemagic, Yvonne Puplampu-Dove, Shradha Patel, Eli Gilboa
T cell immunoglobulin-3 (TIM-3) is a negative regulator of interferon-γ (IFN-γ) secreting CD4(+) T cells and CD8(+) T cytotoxic cells. Recent studies have highlighted the role of TIM-3 as an important mediator of CD8(+) T cell exhaustion in the setting of chronic viral infections and cancer. In murine tumor models, antibody blockade of TIM-3 with anti-TIM-3 antibodies as monotherapy has no or minimal antitumor activity, suggesting that TIM-3 signaling exerts an accessory or amplifying effect in keeping immune responses in check...
August 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28800924/the-influence-of-macrophage-growth-factors-on-theiler-s-murine-encephalomyelitis-virus-tmev-infection-and-activation-of-macrophages
#16
Karin M Schneider, Neva B Watson, Scott B Minchenberg, Paul T Massa
Macrophages are common targets for infection and innate immune activation by many pathogenic viruses including the neurotropic Theiler's Murine Encephalomyelitis Virus (TMEV). As both infection and innate activation of macrophages are key determinants of viral pathogenesis especially in the central nervous system (CNS), an analysis of macrophage growth factors on these events was performed. C3H mouse bone-marrow cells were differentiated in culture using either recombinant macrophage colony stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), inoculated with TMEV (BeAn) and analyzed at various times thereafter...
August 8, 2017: Cytokine
https://www.readbyqxmd.com/read/28799270/non-activated-titanium-dioxide-nanoparticles-promote-the-growth-of-chlamydia-trachomatis-and-decrease-the-antimicrobial-activity-of-silver-nanoparticles
#17
Anita Bogdanov, László Janovák, Ildikó Lantos, Valéria Endrész, Dániel Sebők, Tamás Szabó, Imre Dékány, Judit Deák, Zsolt Rázga, Katalin Burián, Dezső P Virok
AIMS: Chlamydia trachomatis and herpes simplex virus are the most prevalent bacterial and viral sexually transmitted infections. Due to the chronic nature of their infections, they are able to interact with titanium-dioxide nanoparticles applied as food additives or drug delivery vehicles. The aim of our study was to describe the interactions of these two prevalent pathogens with the titanium-dioxide nanoparticles. METHODS AND RESULTS: Chlamydia trachomatis and herpes simplex virus-2 were treated with non-activated titanium-dioxide nanoparticles, silver nanoparticles and silver decorated titanium-dioxide nanoparticles before infection of HeLa and Vero cells...
August 11, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28798895/prevalence-and-identification-of-serum-markers-associated-with-vertical-transmission-of-hepatitis-b-in-pregnant-women-in-yaounde-cameroon
#18
Lucien Honoré Etame Sone, Roger Ahouga Voufo, Henriette Thérèse Dimodi, Michel Kengne, Cédric Gueguim, Nnanga Ngah, Julius Oben, Judith Laure Ngondi
OBJECTIVE: To determine the prevalence of Hepatitis B Virus (HBV) infection in pregnant women and identify markers associated with vertical transmission of HBV. METHODS: Prospective and cross-sectional study over 10 months on 298 pregnant women attending antenatal clinics in the Cité Verte and Efoulan District hospitals in Cameroon. A dry tube blood collection was performed on all pregnant women and babies born to HBsAg-positive mothers. Serum from the women was used to test for HBsAg through immunochromatography and then confirmed by ELISA...
2017: International Journal of MCH and AIDS
https://www.readbyqxmd.com/read/28798382/chronic-low-level-expression-of-hiv-1-tat-promotes-a-neurodegenerative-phenotype-with-aging
#19
Alex M Dickens, Seung Wan Yoo, Alfred C Chin, Jiadi Xu, Tory P Johnson, Amanda L Trout, Kurt F Hauser, Norman J Haughey
The widespread use of combinational antiretroviral therapies (cART) in developed countries has changed the course of Human Immunodeficiency Virus (HIV) infection from an almost universally fatal disease to a chronic infection for the majority of individuals. Although cART has reduced the severity of neurological damage in HIV-infected individuals, the likelihood of cognitive impairment increases with age, and duration of infection. As cART does not suppress the expression of HIV non-structural proteins, it has been proposed that a constitutive production of HIV regulatory proteins in infected brain cells may contribute to neurological damage...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798348/fas-ligand-mediated-cytotoxicity-of-cd4-t-cells-during-chronic-retrovirus-infection
#20
Anna Malyshkina, Elisabeth Littwitz-Salomon, Kathrin Sutter, Gennadiy Zelinskyy, Sonja Windmann, Simone Schimmer, Annette Paschen, Hendrik Streeck, Kim J Hasenkrug, Ulf Dittmer
CD4+ helper T cells and cytotoxic CD8+ T cells are key players for adaptive immune responses against acute infections with retroviruses. Similar to textbook knowledge the most important function of CD4+ T cells during an acute retrovirus infection seems to be their helper function for other immune cells. Whereas there was no direct anti-viral activity of CD4+ T cells during acute Friend Virus (FV) infection, they were absolutely required for the control of chronic infection. During chronic FV infection a population of activated FV-specific CD4+ T cells did not express cytotoxic molecules, but Fas Ligand that can induce Fas-induced apoptosis in target cells...
August 10, 2017: Scientific Reports
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