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https://www.readbyqxmd.com/read/30337056/tumor-necrosis-factor-inhibitors-and-risk-of-peripheral-neuropathy-in-patients-with-rheumatic-diseases
#1
Mahyar Etminan, Mohit Sodhi, Ali Samii, Bruce C Carleton, Abbas Kezouh, Juan Antonio Avina-Zubieta
IMPORTANCE: Tumor necrosis factor inhibitors (TNFi) are widely used in the treatment of a variety of autoimmune diseases. A number of case reports have linked TNFi to neurologic adverse events including peripheral neuropathy (PN) in patients with rheumatic diseases. OBJECTIVES: To quantify the risk of peripheral neuropathy with TNFi in patients with rheumatic diseases. DESIGN: Nested-Case Control study within a cohort of patients with rheumatic diseases...
September 27, 2018: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/30333622/cryo-em-structure-of-the-ebola-virus-nucleoprotein-rna-complex-at-3-6-%C3%A3-resolution
#2
Yukihiko Sugita, Hideyuki Matsunami, Yoshihiro Kawaoka, Takeshi Noda, Matthias Wolf
Ebola virus causes haemorrhagic fever with a high fatality rate in humans and non-human primates. It belongs to the family Filoviridae in the order Mononegavirales, which are viruses that contain linear, non-segmented, negative-sense, single-stranded genomic RNA1,2 . The enveloped, filamentous virion contains the nucleocapsid, consisting of the helical nucleoprotein-RNA complex, VP24, VP30, VP35 and viral polymerase1,3 . The nucleoprotein-RNA complex acts as a scaffold for nucleocapsid formation and as a template for RNA replication and transcription by condensing RNA into the virion4,5 ...
October 17, 2018: Nature
https://www.readbyqxmd.com/read/30326556/role-of-host-cell-secretory-machinery-in-zika-virus-life-cycle
#3
REVIEW
Garrett Sager, Samuel Gabaglio, Elizabeth Sztul, George A Belov
The high human cost of Zika virus infections and the rapid establishment of virus circulation in novel areas, including the United States, present an urgent need for countermeasures against this emerging threat. The development of an effective vaccine against Zika virus may be problematic because of the cross reactivity of the antibodies with other flaviviruses leading to antibody-dependent enhancement of infection. Moreover, rapidly replicating positive strand RNA viruses, including Zika virus, generate large spectrum of mutant genomes (quasi species) every replication round, allowing rapid selection of variants resistant to drugs targeting virus-specific proteins...
October 15, 2018: Viruses
https://www.readbyqxmd.com/read/30322148/development-of-novel-intramolecular-fret-based-abc-transporter-biosensors-to-identify-new-substrates-and-modulators
#4
Bremansu Osa-Andrews, Kee W Tan, Angelina Sampson, Surtaj H Iram
Multidrug resistance protein 1 (MRP1) can efflux a wide variety of molecules including toxic chemicals, drugs, and their derivatives out of cells. Substrates of MRP1 include anti-cancer agents, antibiotics, anti-virals, anti-human immunodeficiency virus (HIV), and many other drugs. To identify novel substrates and modulators of MRP1 by exploiting intramolecular fluorescence resonance energy transfer (FRET), we genetically engineered six different two-color MRP1 proteins by changing green fluorescent protein (GFP) insertion sites, while keeping the red fluorescent protein (RFP) at the C-terminal of MRP1...
October 13, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/30319994/the-hepatitis-b-surface-antigen-binding-protein-an-immunoglobulin-g-constant-region-like-protein-that-interacts-with-hbv-envelop-proteins-and-mediates-hbv-entry
#5
Yeping Sun, Shanshan Wang, Yong Yi, Jing Zhang, Zhongping Duan, Kehu Yuan, Wenjun Liu, Jing Li, Yiping Zhu
Hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis, liver cancer, and liver failure, affecting 350 million people worldwide. Currently available anti-HBV drugs include (PEGylated-) interferon-α and nucleos(t)ide analogs, which can cause significant side effects and drug-resistance in many cases of long-term treatment. The lack of a reliable and robust in vitro infection system is a major barrier for understanding the HBV life cycle and discovering novel therapeutic targets. In the present study, we demonstrate that overexpression of the hepatitis B surface antigen binding protein (SBP) in HepG2 cells (HepG2-SBP) resulted in their susceptibility to HBV infection...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/30319596/-aloe-polysaccharides-inhibit-influenza-a-virus-infection-a-promising-natural-anti-flu-drug
#6
Zhenhong Sun, Cuilian Yu, Wei Wang, Guangfu Yu, Tingting Zhang, Lin Zhang, Jiguo Zhang, Kai Wei
Influenza A virus causes periodic outbreaks and seriously threatens human health. The drug-resistant mutants have shown an epidemic trend because of the abuse of chemical drugs. Aloe polysaccharides (APS) extracted from Aloe vera leaves have evident effects on the therapy of virus infection. However, the activity of APS in anti-influenza virus has yet to be investigated. Here, we refined polysaccharides from A. vera leaf. In vitro test revealed that APS could inhibit the replication of a H1N1 subtype influenza virus, and the most obvious inhibitory effect was observed in the viral adsorption period...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30319402/magnesium-isoglycyrrhizinate-ameliorates-fibrosis-and-disrupts-tgf-%C3%AE-mediated-smad-pathway-in-activated-hepatic-stellate-cell-line-lx2
#7
Jie Kai Tee, Fei Peng, Yeong Lan Tan, Bo Yu, Han Kiat Ho
Liver fibrosis is a histological change often attributed to the activation of hepatic stellate cells (HSCs) and the excessive formation of scar tissues in the liver. Advanced stages of the disease frequently lead to cirrhosis. Magnesium isoglycyrrhizinate (MgIG) has been accepted as a hepatoprotective drug with the potential of alleviating inflammatory conditions and thus promote liver recovery from viral- or drug-induced injury. While MgIG has been empirically integrated into the clinics to treat some liver diseases, its anti-fibrotic effect and the associated mechanisms remain poorly characterized...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30315966/dioscin-a-diverse-acting-natural-compound-with-therapeutic-potential-in-metabolic-diseases-cancer-inflammation-and-infections
#8
REVIEW
Xufeng Tao, Lianhong Yin, Lina Xu, Jinyong Peng
Currently, the numbers of patients with cancer, fibrosis, diabetes, chronic kidney disease, stroke and osteoporosis are increasing fast and fast. It's critical necessary to discovery lead compounds for new drug development. Dioscin, one active compound in some medicinal plants, has anti-inflammation, immunoregulation, hypolipidemic, anti-viral, anti-fungal and anti-allergic effects. In recent years, dioscin has reached more and more attention with its potent effects to treat liver, kidney, brain, stomach and intestine damages, and metabolic diseases including diabetes, osteoporosis, obesity, hyperuricemia as well as its anti-cancer activities through adjusting multiple targets and multiple signals...
October 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30307344/safety-and-effectiveness-of-conventional-systemic-therapy-and-biological-drugs-in-patients-with-moderate-to-severe-psoriasis-and-hiv-infection-a-retrospective-multicenter-study
#9
A Montes-Torres, G Aparicio, R Rivera, E Vilarrasa, M Marcellán, J Notario, C Soria, I Belinchón, P de la Cueva, M Ferrán, J M Carrascosa, F J Gómez, L Salgado, M Velasco, M A Descalzo, I García-Doval, E Daudén
BACKGROUND: The management of HIV-positive patients with psoriasis is controversial and limited to individual cases or short series of patients. OBJECTIVES: To evaluate the safety and effectiveness of conventional and biologic immunosuppressive drugs in the treatment of patients with psoriasis and concomitant HIV infection. METHODS: A retrospective multicenter study was conducted. The study included data from 2008 to 2016. Inclusion criteria were: HIV adult patients with moderate-to-severe psoriasis, HIV viral load determinations at baseline and at least after 6 months of treatment, and systemic immunosuppressive treatment for at least 6 months...
October 11, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/30306175/sulfono-%C3%AE-aa-modified-peptides-that-inhibit-hiv-1-fusion
#10
Olapeju Bolarinwa, Meng Zhang, Erin Mulry, Min Lu, Jianfeng Cai
The utilization of bioactive peptides in the development of highly selective and potent pharmacological agents for the disruption of protein-protein interactions is appealing for drug discovery. It is known that HIV-1 entry into a host cell is through a fusion process that is mediated by the trimeric viral glycoprotein gp120/41, which is derived from gp160 through proteolytic processing. Peptides derived from the HIV gp41 C-terminus have proven to be potent in inhibiting the fusion process. These peptides bind tightly to the hydrophobic pocket on the gp-41 N-terminus, which was previously identified as a potential inhibitor binding site...
October 11, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/30300716/micafungin-is-a-novel-anti-viral-agent-of-chikungunya-virus-through-multiple-mechanisms
#11
Yi-Jung Ho, Feng-Cheng Liu, Chia-Tsui Yeh, Chuen Mi Yang, Chang-Chi Lin, Te-Yu Lin, Po-Shiuan Hsieh, Ming-Kuan Hu, Zhiyuan Gong, Jeng-Wei Lu
The chikungunya virus (CHIKV) is a mosquito-borne virus that belongs to the genus Alphavirus, family Togaviridae. It is the cause of chikungunya fever in humans, which presents a serious global threat due to its high rate of contagion. The clinical symptoms of CHIKV include fever and persistent, severe arthritis. Micafungin has broad-spectrum fungicidal activity against Candida spp. is a promising echinocandin that was recently approved by the U.S. Food and Drug Administration (FDA) and has demonstrated activity against Candida and Aspergillus...
November 2018: Antiviral Research
https://www.readbyqxmd.com/read/30295428/herpes-zoster-in-tofacitinib-risk-is-further-increased-with-glucocorticoids-but-not-methotrexate
#12
Jeffrey R Curtis, Fenglong Xie, Shuo Yang, Sasha Bernatsky, Lang Chen, Huifeng Yun, Kevin Winthrop
BACKGROUND: Increased herpes zoster (HZ) has been observed with janus kinase inhibitors such as tofacitinib. However, it is unclear whether concomitant methotrexate (MTX) and/or glucocorticoids (GC) confer additional (additive or multiplicative) risk. We evaluated HZ risk in tofacitinib users with and without MTX and GC. METHODS: Within MarketScan and Medicare data (2011-2016) we identified all rheumatologist-diagnosed RA patients initiating tofacitinib (index date); demographics and baseline covariates were evaluated in the year prior to index date...
October 8, 2018: Arthritis Care & Research
https://www.readbyqxmd.com/read/30282696/anti-%C3%AE-4%C3%AE-7-therapy-targets-lymphoid-aggregates-in-the-gastrointestinal-tract-of-hiv-1-infected-individuals
#13
Mathieu Uzzan, Minami Tokuyama, Adam K Rosenstein, Costin Tomescu, Ivo N SahBandar, Huaibin M Ko, Louise Leyre, Anupa Chokola, Emma Kaplan-Lewis, Gabriela Rodriguez, Akihiro Seki, Michael J Corley, Judith Aberg, Annalena La Porte, Eun-Young Park, Hideki Ueno, Ioannis Oikonomou, Itai Doron, Iliyan D Iliev, Benjamin K Chen, Jennifer Lui, Timothy W Schacker, Glaucia C Furtado, Sergio A Lira, Jean-Frederic Colombel, Amir Horowitz, Jean K Lim, Nicolas Chomont, Adeeb H Rahman, Luis J Montaner, Lishomwa C Ndhlovu, Saurabh Mehandru
Gut homing CD4+ T cells expressing the integrin α4β7 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although simianized anti-α4β7 monoclonal antibodies have shown promise in preventing or attenuating the disease course of simian immunodeficiency virus in nonhuman primate studies, the mechanisms of drug action remain elusive. We present a cohort of individuals with mild inflammatory bowel disease and concomitant HIV-1 infection receiving anti-α4β7 treatment...
October 3, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/30282040/the-kinase-activity-of-hematopoietic-progenitor-kinase-1-is-essential-for-the-regulation-of-t-cell-function
#14
Sairy Hernandez, Jing Qing, Rebecca Hong Thibodeau, Xiangnan Du, Summer Park, Hyang-Mi Lee, Min Xu, Soyoung Oh, Armando Navarro, Meron Roose-Girma, Robert J Newman, Soren Warming, Michelle Nannini, Deepak Sampath, Jeong M Kim, Jane L Grogan, Ira Mellman
We examined hematopoietic protein kinase 1 (HPK1), whose reliance on scaffold versus kinase functions for negative immune cell regulation is poorly understood and critical to its assessment as a viable drug target. We identify kinase-dependent roles for HPK1 in CD8 T cells that restrict their anti-viral and anti-tumor responses by using HPK1 kinase-dead (HPK1.kd) knockin mice. Loss of HPK1 kinase function enhanced T cell receptor signaling and cytokine secretion in a T-cell-intrinsic manner. In response to chronic lymphocytic choriomeningitis virus (LCMV) infection or tumor challenge, viral clearance and tumor growth inhibition were enhanced in HPK1...
October 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/30274122/novel-core-shell-dextran-hybrid-nanosystem-for-anti-viral-drug-delivery
#15
K S Joshy, Anne George, S Snigdha, Blessy Joseph, Nandakumar Kalarikkal, Laly A Pothen, Sabu Thomas
Zidovudine (AZT) is an antiviral drug extensively used for combating the global pandemic- HIV/AIDS. However, its uses are overshadowed by its short half -life, poor aqueous solubility and inability to cross physiological barriers. This study highlights a nanosystem consisting of dextran and stearic acid for AZT delivery. This hybrid nanoparticle was prepared by double emulsion solvent evaporation method. The morphological analysis of the prepared nanoparticles was carried out by transmission electron microscopy (TEM) and structural analysis through FTIR spectroscopy...
December 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/30270601/influence-of-pretreatment-with-immunosuppressive-drugs-on-viral-proliferation
#16
Ga-Eun Lee, Cha-Gyun Shin
Immunosuppressive drugs are used to make the body less likely to reject transplanted organs or to treat autoimmune diseases. In this study, five immunosuppressive drugs including two glucocorticoids (dexamethasone and prednisolone), one calcineurin inhibitor (cyclosporin A), one non-steroid anti-inflammatory drug (aspirin), and one antimetabolite (methotrexate) were tested for their effects on viral proliferation using feline foamy virus (FFV). The five drugs had different cytotoxic effects on the Crandell-Ress feline kidney (CRFK) cells, the natural host cell of FFV...
September 20, 2018: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/30268939/non-target-strategies-by-hrms-to-evaluate-fluidized-micro-grain-activated-carbon-as-a-tertiary-treatment-of-wastewater
#17
A Bergé, A Buleté, A Fildier, R Mailler, J Gasperi, Y Coquet, F Nauleau, V Rocher, E Vulliet
Among the release solutions for reducing the discharge of organic and persistent contaminants in the aquatic environment, the use of a tertiary treatment in addition to existing conventional wastewater treatment processes is considered. The use of micro-grain activated carbon in a fluidized bed is a promising technique investigated in this study. The effluents from a large-scale pilot system were analyzed by liquid chromatography coupled with high-resolution mass spectrometry (QToF). Several strategies were deployed, namely molecular fingerprint comparison, suspected and non-target analyses, identification of refractory compounds to treatment, and finally, quantification of identified compounds...
December 2018: Chemosphere
https://www.readbyqxmd.com/read/30268914/novel-cytomegalovirus-inhibitory-compounds-of-the-class-pyrrolopyridines-show-a-complex-pattern-of-target-binding-that-suggests-an-unusual-mechanism-of-antiviral-activity
#18
Friedrich Hahn, Corina Hutterer, Christophe Henry, Stuart T Hamilton, Hanife Strojan, Alexandra Kraut, Ulrike Schulte, Martin Schütz, Stephan Kohrt, Christina Wangen, José Pfizer, Yohann Couté, William D Rawlinson, Stefan Strobl, Manfred Marschall
Human cytomegalovirus (HCMV) is a major human pathogen with seropositivity rates in the adult population ranging between 40% and 95%. HCMV infection is associated with severe pathology, such as life-threatening courses of infection in immunocompromised individuals and neonates. Current standard therapy with valganciclovir has the disadvantage of adverse side effects and viral drug resistance. A novel anti-HCMV drug, letermovir, has been approved recently, so that improved therapy options are available. Nevertheless, even more so far unexploited classes of compounds and molecular modes of action will be required for a next generation of antiherpesviral treatment strategies...
September 27, 2018: Antiviral Research
https://www.readbyqxmd.com/read/30261763/an-update-on-the-recent-advances-in-antifibrotic-therapy
#19
Frank Tacke, Ralf Weiskirchen
Chronic injury to the liver, such as viral hepatitis, alcoholism, non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), promotes extracellular matrix deposition and organ scarring, termed hepatic fibrosis. Fibrosis might progress to cirrhosis and predisposes to hepatocellular carcinoma (HCC), but is also associated with extrahepatic morbidity and mortality in NAFLD/NASH. The improved understanding of pathogenic mechanisms underlying chronic inflammation and fibrogenesis in the liver prompted recent advances in antifibrotic therapies...
September 27, 2018: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/30261071/inactivation-of-human-and-avian-influenza-viruses-by-potassium-oleate-of-natural-soap-component-through-exothermic-interaction
#20
Takayoshi Kawahara, Isamu Akiba, Megumi Sakou, Takemasa Sakaguchi, Hatsumi Taniguchi
An influenza epidemic is still a problem despite the development of vaccines and anti-influenza drugs. Preventive measures such as handwashing are fundamental and important for counteracting influenza virus infection. In this study, we clarified the anti-influenza virus effects of surfactants, which are the main components of hand soaps for hand washing: potassium oleate (C18:1), sodium laureth sulfate (LES) and sodium lauryl sulfate (SDS). For a human influenza virus strain (H3N2), C18:1 reduced the infectivity by 4 logs or more, whereas LES and SDS reduced the infectivity by 1 log or less...
2018: PloS One
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