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https://www.readbyqxmd.com/read/28542609/potent-and-selective-inhibition-of-pathogenic-viruses-by-engineered-ubiquitin-variants
#1
Wei Zhang, Ben A Bailey-Elkin, Robert C M Knaap, Baldeep Khare, Tim J Dalebout, Garrett G Johnson, Puck B van Kasteren, Nigel J McLeish, Jun Gu, Wenguang He, Marjolein Kikkert, Brian L Mark, Sachdev S Sidhu
The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses...
May 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28541554/activation-of-group-2-innate-lymphoid-cells-exacerbates-and-confers-corticosteroid-resistance-to-mouse-nasal-type-2-inflammation
#2
Taiyo Morikawa, Ayumi Fukuoka, Kazufumi Matsushita, Koubun Yasuda, Naruhito Iwasaki, Shoko Akasaki, Shigeharu Fujieda, Tomohiro Yoshimoto
Both Th2 cells and group 2 innate lymphoid cells (ILC2s) contribute to allergic diseases. However, their exact role and relationship in nasal allergic disorders is unclear. In this study, we investigated the cooperation of Th2 cells and ILC2s in a mouse model of nasal allergic disorder. To differentially activate Th2 cells and/or ILC2s in nasal mucosa, mice were intranasally administered ovalbumin (OVA) antigen, papain, an ILC2-activator, or both for 2 weeks. Epithelial thickness and number of eosinophils in the nasal mucosa were evaluated at 24 hours after the final challenge...
May 25, 2017: International Immunology
https://www.readbyqxmd.com/read/28531982/study-of-the-keratin-based-therapeutic-dermal-patches-for-the-delivery-of-bioactive-molecules-for-wound-treatment
#3
Kush Kumar Nayak, Pratima Gupta
In the present study, dressing materials were fabricated in the form of dermal patches. The keratin based biocompatible materials, namely Keratin/Alginate, Keratin/Agar, and Keratin/Gellan were developed as therapeutic dermal patches. The patches were coated with green synthesized silver nanoparticles to prevent the microbial infection and were found to be antimicrobial against pathogens. Papain was used in the patches to acquire the enzymatic cell debridement and its activity was measured by reduction rate of benzoyl-l-arginine ethyl ester...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531096/the-lys-asp-tyr-triad-within-the-mite-allergen-der-p-1-propeptide-is-a-critical-structural-element-for-the-ph-dependent-initiation-of-the-protease-maturation
#4
Andy Chevigné, Vincenzo Campizi, Martyna Szpakowska, David Bourry, Marie-Eve Dumez, José C Martins, André Matagne, Moreno Galleni, Alain Jacquet
The major house dust mite allergen, Der p 1, is a papain-like cysteine protease expressed as an inactive precursor, proDer p 1, carrying an N-terminal propeptide with a unique structure. The maturation of the zymogen into an enzymatically-active form of Der p 1 is a multistep autocatalytic process initiated under acidic conditions through conformational changes of the propeptide, leading to the loss of its inhibitory ability and its subsequent gradual cleavage. The aims of this study were to characterize the residues present in the Der p 1 propeptide involved in the initiation of the zymogen maturation process, but also to assess the impact of acidic pH on the propeptide structure, the activity of Der p 1 and the fate of the propeptide...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28512541/anti-plaque-and-anti-gingivitis-effect-of-papain-bromelain-miswak-and-neem-containing-dentifrice-a-randomized-controlled-trial
#5
Abhinav Tadikonda, Kalyana-Chakravarthy Pentapati, Arun-Sreenivas Urala, Shashidhar Acharya
BACKGROUND: Patients undergoing fixed orthodontic therapy may have difficulty in maintaining a good oral hygiene due to the difficulty posed by the appliances in accessing such areas. This study aimed to compare anti-plaque and anti-gingivitis efficacy of dentifrice containing Papain, Bromelain, Miswak and Neem with a standard dentifrice among patient's undergoing fixed orthodontic treatment. MATERIAL AND METHODS: Single center, single blind, parallel arm, randomized controlled clinical trial with an allocation ratio of 1:1 was conducted...
May 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28504174/pineapple-peel-carboxymethyl-cellulose-polyvinyl-alcohol-mesoporous-silica-sba-15-hydrogel-composites-for-papain-immobilization
#6
Hongjie Dai, Shiyi Ou, Zhijun Liu, Huihua Huang
Hydrogel composites based on pineapple peel carboxymethyl cellulose, polyvinyl alcohol and mesoporous silica SBA-15 were synthesized by an eco-friendly method of repeated freeze-thaw cycles for the application of papain immobilization. The experiment was optimized to obtain an efficient papain immobilization carrier. Simultaneously the immobilization conditions, including enzyme concentration, pH, crosslinker concentration and cross-linking time were optimized. The immobilized papain had maximum activity at low reaction temperature of 40°C and showed pH-sensitivity by exhibiting a rapid decrease of activity within a narrow range from pH 7...
August 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28501446/the-involvement-of-cathepsin-f-gene-ctsf-in-turbot-scophthalmus-maximus-l-mucosal-immunity
#7
Chengbin Gao, Qiang Fu, Baofeng Su, Huanhuan Song, Shun Zhou, Fenghua Tan, Chao Li
Cathepsin F (CTSF) is a recently described papain-like cysteine protease and unique among cathepsins due to an elongated N-terminal pro-region, which contains a cystatin domain. CTSF likely plays a regulatory role in processing the invariant chain which is associated with the major histocompatibility complex (MHC) class II. In this regard, we identified the CTSF gene of turbot as well as its protein structure, phylogenetic relationships, and expression patterns in mucosal tissues following Vibrio anguillarum and Streptococcus iniae challenge...
May 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28497586/r-ras-deficiency-does-not-affect-papain-induced-ige-production-in-mice
#8
Laura Kummola, Zsuzsanna Ortutay, Maria Vähätupa, Stuart Prince, Hannele Uusitalo-Järvinen, Tero A H Järvinen, Ilkka S Junttila
INTRODUCTION: R-Ras GTPase has recently been implicated in the regulation of immune functions, particularly in dendritic cell (DC) maturation, immune synapse formation, and subsequent T cell responses. METHODS: Here, we investigated the role of R-Ras in allergen-induced immune response (type 2 immune response) in Rras deficient (R-Ras KO) and wild type (WT) mice. RESULTS: Initially, we found that the number of conventional DC's in the lymph nodes (LNs) was reduced in R-Ras KO mice...
May 11, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28496948/evaluation-of-igy-antibody-as-a-polyspecific-coombs-reagent
#9
Esteban Justo Gutiérrez Calzado, Marlene Toledano Heredia, Jeorge Fernadez Duharte, Amir-Hassan Zarnani
BACKGROUND: During the last twenty years, the extraction of specific egg yolk (IgY) antibodies from the immunized chickens has been accepted as a useful alternative to the immunization of mammals. The aim of the present study was immunizing the chickens with Human Umbilical Cord Serum (HUCS) and the extraction of specific anti-human globulins (IgG, C3b, and C3d) antibodies from egg yolk in order to obtain polyspecific Coombs reagent. METHODS: The novelty of this work was the achievement of a polyclonal reagent through a very cheap alternative method in accordance with all ethical regulations required for obtaining it...
April 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28496946/alpha-alumina-nanoparticle-conjugation-to-cysteine-peptidase-a-and-b-an-efficient-method-for-autophagy-induction
#10
Fatemeh Beyzay, Ahmad Zavaran Hosseini, Sara Soudi
BACKGROUND: Autophagy as a cellular pathway facilitates several immune responses against infection. It also eliminates invading pathogens through transferring content between the cytosol and the lysosomal vesicles and contributes to the cross-presentation of exogenous antigens to T lymphocytes via MHC class I pathway. Autophagy induction is one of the main targets for new drugs and future vaccine formulations. Nanoparticles are one of the candidates for autophagy induction. Cysteine Peptidase A (CPA) and Cysteine Peptidase B (CPB) are two members of papain family (Clan CA, family C1) enzyme that have been considered as a virulence factor of Leishmania (L...
April 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28493022/in-vitro-anti-thrombotic-and-anti-coagulant-properties-of-blacklip-abalone-haliotis-rubra-viscera-hydrolysate
#11
Hafiz Ansar Rasul Suleria, Paul P Masci, Rama Addepalli, Wei Chen, Glenda C Gobe, Simone A Osborne
Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti-coagulant activities. In this study, a hydrolysate was prepared from blacklip abalone (Haliotis rubra) viscera using papain and bromelain and fractionated using ion exchange and size exclusion chromatography. Hydrolysates and fractions were investigated for in vitro thrombin inhibition mediated through heparin cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16...
May 11, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28490584/a-naturally-occurring-recombinant-enterovirus-expresses-a-torovirus-deubiquitinase
#12
Pengcheng Shang, Saurav Misra, Ben Hause, Ying Fang
Enteroviruses are implicated in a wide range of diseases in human and animals. In this study, a novel enterovirus (species G; EVG 08/NC_USA/2015) was isolated from a diagnostic sample of neonatal pig diarrhea case and identified using metagenomics and complete genome sequencing. The viral genome shares 75.4% nucleotide identity with a prototypic EVG strain (PEV9 UKG/410/73). Remarkably, a 582 nucleotide insertion, flanked by 3C(pro) cleavage sites at 5' - and 3' - ends, was found in the 2C/3A junction region of the viral genome...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28485427/chemoenzymatic-synthesis-of-polypeptides-containing-the-unnatural-amino-acid-2-aminoisobutyric-acid
#13
Kousuke Tsuchiya, Keiji Numata
Polypeptides containing 2-aminoisobutyric acid (Aib) units as an unnatural amino acid residue were synthesized by papain-catalyzed chemoenzymatic polymerization of a tripeptide ethyl ester l-Ala-Aib-l-Ala-OEt in an aqueous medium. The Aib-containing polypeptide adopted an α-helix conformation in both the solid and solution phases, which was induced by the periodic Aib residue.
May 9, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28484087/modulation-of-goat-monocyte-function-by-hccyst-2-a-secreted-cystatin-from-haemonchus-contortus
#14
Yujian Wang, Yuling Wen, Shuai Wang, Muhammad Ehsan, RuoFeng Yan, XiaoKai Song, LiXin Xu, XiangRui Li
Modulation and suppression of the host immune response by nematode parasites have been reported extensively and the cysteine protease inhibitor (cystatin) is identified as one of the major immunomodulator. In the present study, we cloned and produced recombinant cystatin protein from nematode parasite Haemonchus contortus (rHCcyst-2) and investigated its immunomodulatory effects on goat monocyte. rHCcyst-2 protein is biologically functional as shown by its ability to inhibit the protease activity of cathepsin L, cathepsin B and papain...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28467807/the-antigen-binding-fragment-of-human-gamma-immunoglobulin-prevents-amyloid-%C3%AE-peptide-folding-into-%C3%AE-sheet-to-form-oligomers
#15
Victòria Valls-Comamala, Biuse Guivernau, Jaume Bonet, Marta Puig, Alex Perálvarez-Marín, Ernest Palomer, Xavier Fernàndez-Busquets, Xavier Altafaj, Marta Tajes, Albert Puig-Pijoan, Rubén Vicente, Baldomero Oliva, Francisco J Muñoz
The amyloid beta-peptide (Aβ) plays a leading role in Alzheimer's disease (AD) physiopathology. Even though monomeric forms of Aβ are harmless to cells, Aβ can aggregate into β-sheet oligomers and fibrils, which are both neurotoxic. Therefore, one of the main therapeutic approaches to cure or delay AD onset and progression is targeting Aβ aggregation. In the present study, we show that a pool of human gamma immunoglobulins (IgG) protected cortical neurons from the challenge with Aβ oligomers, as assayed by MTT reduction, caspase-3 activation and cytoskeleton integrity...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28460927/angiotensin-i-converting-enzyme-inhibitory-peptides-from-bovine-collagen-insights-into-inhibitory-mechanism-and-transepithelial-transport
#16
Yu Fu, Jette Feveile Young, Martin Krøyer Rasmussen, Trine Kastrup Dalsgaard, René Lametsch, Rotimi E Aluko, Margrethe Therkildsen
The inhibitory mechanism and transepithelial transport of angiotensin I-converting enzyme (ACE)-inhibitory peptides (VGPV and GPRGF) derived from Alcalase®- and papain-hydrolyzed bovine collagen were investigated. The inhibitory mechanism of VGPV and GPRGF was experimentally determined to be non-competitive and the results were supported by molecular docking data. In silico and in vitro gastrointestinal digestion indicated that VGPV remained resistant to digestive enzymes, while GPRGF was degraded into smaller ACE-inhibitory peptides (GPR and GF)...
November 2016: Food Research International
https://www.readbyqxmd.com/read/28438633/structural-insights-into-the-interaction-of-coronavirus-papain-like-proteases-and-interferon-stimulated-gene-product-15-from-different-species
#17
Courtney M Daczkowski, John V Dzimianski, Jozlyn R Clasman, Octavia Goodwin, Andrew D Mesecar, Scott D Pegan
Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication and antagonize the host innate immune response. The latter function involves reversing the post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon-stimulated gene product 15 (ISG15). Ub is known to be highly conserved among eukaryotes, but surprisingly, ISG15 is highly divergent among animals...
April 21, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28420819/synonymous-and-biased-codon-usage-by-mers-cov-papain-like-and-3cl-proteases
#18
Mahmoud Kandeel, Abdallah Altaher
Middle East respiratory syndrome coronavirus (MERS CoV) is a recently evolved fatal respiratory disease that poses a concern for a global epidemic. MERS CoV encodes 2 proteases, 3C-like protease (3CLpro) and papain-like protease (PLpro). These proteases share in processing MERS CoV polyproteins at different sites to yield 16 nonstructural proteins. In this work, we provide evidence that MERS CoV 3CLpro and PLpro are subject to different genetic and evolutionary influences that shape the protein sequence, codon usage pattern, and codon usage bias...
April 18, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28414040/sars-coronavirus-papain-like-protease-up-regulates-the-collagen-expression-through-non-samd-tgf-%C3%AE-1-signaling
#19
Ching-Ying Wang, Chien-Yi Lu, Shih-Wen Li, Chien-Chen Lai, Chun-Hung Hua, Su-Hua Huang, Ying-Ju Lin, Mann-Jen Hour, Cheng-Wen Lin
SARS coronavirus (CoV) papain-like protease (PLpro) reportedly induced the production of TGF-β1 through p38 MAPK/STAT3-meidated Egr-1-dependent activation (Sci. Rep. 6, 25754). This study investigated the correlation of PLpro-induced TGF-β1 with the expression of Type I collagen in human lung epithelial cells and mouse pulmonary tissues. Specific inhibitors for TGF-βRI, p38 MAPK, MEK, and STAT3 proved that SARS-CoV PLpro induced TGF-β1-dependent up-regulation of Type I collagen in vitro and in vivo. Subcellular localization analysis of SMAD3 and SMAD7 indicated that non-SMAD pathways in TGF-β1 signaling involved in the production of Type I collagen in transfected cells with pSARS-PLpro...
April 13, 2017: Virus Research
https://www.readbyqxmd.com/read/28402938/cathepsins-in-digestive-cancers
#20
REVIEW
Siyuan Chen, Hui Dong, Shiming Yang, Hong Guo
Cathepsins are lysosomal peptidases belonging to the papain family, and based on their catalytic sites, these enzymes can be divided into serine, cysteine and aspartic proteases. The studies conducted to date have identified, 15 types of cathepsins that are widely distributed in intracellular and extracellular spaces. These proteases participate in various pathological activities, including the occurrence and development of human cancers. Several recent studies suggest that cathepsins, particularly cathepsins B, D, E and L, contribute to digestive tumorigenesis...
March 29, 2017: Oncotarget
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