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Cathepsin G

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https://www.readbyqxmd.com/read/28800383/epithelial-desquamation-observed-in-a-phase-i-study-of-an-oral-cathepsin-c-inhibitor-gsk2793660
#1
Bruce E Miller, Ruth J Mayer, Navin Goyal, Joanne Bal, Nigel Dallow, Malcolm Boyce, Donald Carpenter, Alison Churchill, Teresa Heslop, Aili L Lazaar
AIMS: Cathepsin C (CTSC) is necessary for the activation of several serine proteases including neutrophil elastase (NE), cathepsin G, and proteinase 3. GSK2793660 is an oral, irreversible inhibitor of CTSC that is hypothesized to provide an alternative route to achieve NE inhibition and was tested in a Phase I study. METHODS: Single escalating oral doses of GSK2793660 0.5 mg to 20 mg or placebo were administered in a randomized crossover design to healthy male subjects; a separate cohort received once daily doses of 12 mg or placebo for 21 days...
August 11, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28797985/the-role-and-mechanism-of-cathepsin-g-in-dermatomyositis
#2
Siming Gao, Honglin Zhu, Huan Yang, Huali Zhang, Qiuxiang Li, Hui Luo
Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by CD4+ T cells and B cells infiltration in perivascular and muscle tissue. Although the infiltration of inflammatory cells plays a key role in muscle damage, the exact mechanism is not clear. Cathepsin G (CTSG) is a member of the serine proteases family and can increase the permeability of vascular endothelial cells and the chemotaxis of inflammatory cells. In this study, we found that the expression of CTSG was increased in peripheral blood mononuclear cells and muscle tissues of DM patients...
August 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28797057/a%C3%AE-42-mediated-proteasome-inhibition-and-associated-tau-pathology-in-hippocampus-are-governed-by-a-lysosomal-response-involving-cathepsin-b-evidence-for-protective-crosstalk-between-protein-clearance-pathways
#3
Karen L G Farizatto, Uzoma S Ikonne, Michael F Almeida, Merari F R Ferrari, Ben A Bahr
Impaired protein clearance likely increases the risk of protein accumulation disorders including Alzheimer's disease (AD). Protein degradation through the proteasome pathway decreases with age and in AD brains, and the Aβ42 peptide has been shown to impair proteasome function in cultured cells and in a cell-free model. Here, Aβ42 was studied in brain tissue to measure changes in protein clearance pathways and related secondary pathology. Oligomerized Aβ42 (0.5-1.5 μM) reduced proteasome activity by 62% in hippocampal slice cultures over a 4-6-day period, corresponding with increased tau phosphorylation and reduced synaptophysin levels...
2017: PloS One
https://www.readbyqxmd.com/read/28740333/mold-alkaloid-cytochalasin-d-modifies-the-morphology-and-secretion-of-fmlp-lps-or-pma-stimulated-neutrophils-upon-adhesion-to-fibronectin
#4
Svetlana I Galkina, Natalia V Fedorova, Marina V Serebryakova, Evgenii A Arifulin, Vladimir I Stadnichuk, Ludmila A Baratova, Galina F Sud'ina
Neutrophils play an essential role in innate immunity due to their ability to migrate into infected tissues and kill microbes with bactericides located in their secretory granules. Neutrophil transmigration and degranulation are tightly regulated by actin cytoskeleton. Invading pathogens produce alkaloids that cause the depolymerization of actin, such as the mold alkaloid cytochalasin D. We studied the effect of cytochalasin D on the morphology and secretion of fMLP-, LPS-, or PMA-stimulated human neutrophils upon adhesion to fibronectin...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28731540/participation-of-osteoclastogenic-factors-in-immunopathogenesis-of-human-chronic-periapical-lesions
#5
S C L T Santos, L A Couto, J M Fonseca, F C A Xavier, A C L Figueiredo, V S Freitas, R A Freitas, J N Santos, A C G Henriques
BACKGROUND: Chronic periapical lesions (CPLs) are common lesions of the oral cavity and are the result of caries, tooth fracture, iatrogenic causes, or factors causing contamination and pulp necrosis. Inflammatory cells participate in the expansion of CPLs by releasing factors that stimulate or inhibit osteolytic activity. The objective of this study was to investigate the participation of RANKL, TNF-α, cathepsin K, IL-33, and OPG in the development of radicular cysts (RCs) and periapical granulomas (PGs)...
July 21, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28726323/characterization-of-a-cathepsin-d-protease-from-cho-cell-free-medium-and-mitigation-of-its-impact-on-the-stability-of-a-recombinant-therapeutic-protein
#6
Amareth Lim, Brandon L Doyle, Gerard M Kelly, Angelia M Reed-Bogan, Lawrence H Breen, Parviz A Shamlou, Peter K Lambooy
During purification process development of a recombinant therapeutic protein, an endoproteolytic activity endogenous to the Chinese hamster ovary (CHO) cells and leading to degradation at particular hydrophobic amino acid residues (e.g., Phe and Trp) was observed when processing at acidic pH. The presence of residual levels of protease activity in purified protein batches affected the inherent activity of the product when stored as a solution. In order to develop a robust purification strategy to minimize this undesirable impact, identification and characterization of this protease was essential to ultimately ensure that a solution formulation was stable for many years...
July 20, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28724439/genetic-deficiency-of-wnt5a-diminishes-disease-severity-in-a-murine-model-of-rheumatoid-arthritis
#7
Susan MacLauchlan, Maria A Zuriaga, José J Fuster, Carla M Cuda, Jennifer Jonason, Fernanda Behzadi, Jennifer Parker Duffen, G Kenneth Haines, Tamar Aprahamian, Harris Perlman, Kenneth Walsh
BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation of the joints, leading to bone erosion and joint dysfunction. Despite the recent successes of disease-modifying anti-rheumatic drugs (DMARDs), there is still clinical need for understanding the development and molecular etiology of RA. Wnts are developmental morphogens whose roles in adult pathology are poorly characterized. Wnt5a is a member of the non-canonical family of Wnts that modulates a wide range of cell processes, including differentiation, migration, and inflammation...
July 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28720327/asymmetric-synthesis-and-evaluation-of-epoxy-%C3%AE-acyloxycarboxamides-as-selective-inhibitors-of-cathepsin-l
#8
Deborah A Dos Santos, Anna Maria Deobald, Vivian E Cornelio, Roberta M D Ávila, Renata C Cornea, Gilberto C R Bernasconi, Marcio W Paixão, Paulo C Vieira, Arlene G Corrêa
Cathepsin L plays important roles in physiological processes as well as in the development of many pathologies. Recently the attentions were turned to its association with tumor progress what makes essential the development of more potent and selective inhibitors. In this work, epoxipeptidomimetics were investigated as new cathepsin inhibitors. This class of compounds is straightforward obtained by using a green one-pot asymmetric epoxidation/Passerini 3-MCR. A small library of 17 compounds was evaluated against cathepsin L, and among them LSPN423 showed to be the most potent...
June 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28702507/brainstem-phenotype-of-cathepsin-a-related-arteriopathy-with-strokes-and-leukoencephalopathy
#9
Yun Tae Hwang, Rahul Lakshmanan, Indran Davagnanam, Andrew G B Thompson, David S Lynch, Henry Houlden, Nin Bajaj, Sofia H Eriksson, Doris-Eva Bamiou, Jason D Warren
No abstract text is available yet for this article.
August 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28691154/digestive-enzyme-ratios-are-good-indicators-of-hatchling-yolk-reserve-and-digestive-gland-maturation-in-early-life-stages-of-cuttlefish-sepia-officinalis-l-application-of-these-new-tools-in-ecology-and-aquaculture
#10
Georges Safi, A S Martinez, C Le Pabic, E Le Bihan, J P Robin, N Koueta
In Sepia officinalis (Linnaeus, 1758), the digestive gland matures during the first month post-hatching, while a shift from intracellular acid to extracellular alkaline digestion occurs. The purpose of this study was to investigate the possibility of using enzymatic ratios for the description of digestive system maturation in early life stages of S. officinalis. Second, it is intended to apply these new tools as eco-physiological indicators for understanding the impact of cuttlefish eggs' life history from different spawning sites of the English Channel on digestive performance of juveniles...
July 10, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28687334/a-cysteine-protease-cathepsin-z-from-disk-abalone-haliotis-discus-discus-genomic-characterization-and-transcriptional-profiling-during-bacterial-infections
#11
G I Godahewa, N C N Perera, Sukkyoung Lee, Myoung-Jin Kim, Jehee Lee
Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. Hence, CTSZ is also acknowledged as an acute-phase protein in host immunity. In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels...
July 4, 2017: Gene
https://www.readbyqxmd.com/read/28683495/osteoimmunology-influence-of-the-immune-system-on-bone-regeneration-and-consumption
#12
Andreas Limmer, Dieter C Wirtz
Background Stimulating bone regeneration is a central aim in orthopaedic and trauma surgery. Although the replacement of bone with artificial materials like cement or apatite helps to keep up bone stability, new bone often cannot be regenerated. Increasing research efforts have led to the clinical application of growth factors stimulating bone growth (e.g. bone morphogenic protein, BMP) and inhibitors preventing bone consumption (e.g. RANKL blocking antibodies). These factors mostly concentrate on stimulating osteoblast or preventing osteoclast activity...
June 2017: Zeitschrift Für Orthopädie und Unfallchirurgie
https://www.readbyqxmd.com/read/28673495/proteomic-profiling-and-differential-messenger-rna-expression-correlate-hsp27-and-serpin-family-b-member-1-to-apical-periodontitis-outcomes
#13
Franco Cavalla, Claudia Biguetti, Sameer Jain, Cleverick Johnson, Ariadne Letra, Gustavo Pompermaier Garlet, Renato Menezes Silva
INTRODUCTION: Understanding protein expression profiles of apical periodontitis may contribute to the discovery of novel diagnostic or therapeutic molecular targets. METHODS: Periapical tissue samples (n = 5) of patients with lesions characterized as nonhealing were submitted for proteomic analysis. Two differentially expressed proteins (heat shock protein 27 [HSP27] and serpin family B member 1 [SERPINB1]) were selected for characterization, localization by immunofluorescence, and association with known biomarkers of acute inflammatory response in human apical periodontitis (n = 110) and healthy periodontal ligaments (n = 26)...
June 30, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28671985/dectin-2-is-a-primary-receptor-for-nlrp3-inflammasome-activation-in-dendritic-cell-response-to-histoplasma-capsulatum
#14
Tzu-Hsuan Chang, Juin-Hua Huang, Hsiu-Chao Lin, Wen-Yu Chen, Yu-Hsiang Lee, Li-Chung Hsu, Mihai G Netea, Jenny P-Y Ting, Betty A Wu-Hsieh
Inflammasome is an intracellular protein complex that serves as cytosolic pattern recognition receptor (PRR) to engage with pathogens and to process cytokines of the interleukin-1 (IL-1) family into bioactive molecules. It has been established that interleukin-1β (IL-1β) is important to host defense against Histoplasma capsulatum infection. However, the detailed mechanism of how H. capsulatum induces inflammasome activation leading to IL-1β production has not been studied. Here, we showed in dendritic cells (DCs) that H...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28670517/comparative-proteomic-analysis-of-tumor-mesenchymal-like-stem-cells-derived-from-high-grade-versus-low-grade-gliomas
#15
Mousa Taghipour, Aydine Omidvar, Mahboobeh Razmkhah, Abbas Ghaderi, Zahra Mojtahedi
OBJECTIVE: Gliomas are the most common primary brain tumors, and have been ranked as the fourth leading cause of cancer death. Tumor mesenchymal-like stem cells (tMSCs) contribute to the aggressive behavior of glial tumors by providing a favorable microenvironment for the malignant cells. The aim of our study was to identify differential proteome of tMSCs derived from low vs. high grade glioma tumors. MATERIALS AND METHODS: Patients with newly diagnosed low and high grade gliomas were included in this case control study...
July 2017: Cell Journal
https://www.readbyqxmd.com/read/28648703/osteoclasts-in-periprosthetic-osteolysis-the-charnley-arthroplasty-revisited
#16
Sebastian S Mukka, Göran N Andersson, Kjell R Hultenby, Olof G Sköldenberg, Joakim P Nordahl, Thomas M Eisler
BACKGROUND: Periprosthetic osteolysis by polyethylene wear debris-triggered osteoclasts is viewed as the main pathophysiological pathway in aseptic loosening in total hip arthroplasty. The present aim was to study osteoclast occurrence in osteolytic lesions in early and late revisions of the Charnley low-friction torque arthroplasty (CLFA). METHODS: Biopsies of the soft interface membrane and the adjacent bone were taken from osteolytic lesions during revision of 16 loose CLFA, early (2-6 years) or late (>10 years) after primary surgery...
May 22, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28644993/long-term-toxicity-of-surface-charged-polystyrene-nanoplastics-to-marine-planktonic-species-dunaliella-tertiolecta-and-artemia-franciscana
#17
E Bergami, S Pugnalini, M L Vannuccini, L Manfra, C Faleri, F Savorelli, K A Dawson, I Corsi
Plastic pollution has been globally recognized as a critical issue for marine ecosystems and nanoplastics constitute one of the last unexplored areas to understand the magnitude of this threat. However, current difficulties in sampling and identifying nano-sized debris make hard to assess their occurrence in marine environment. Polystyrene nanoparticles (PS NPs) are largely used as nanoplastics in ecotoxicological studies and although acute exposures have been already investigated, long-term toxicity on marine organisms is unknown...
June 15, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28625714/proteomic-analysis-of-seminal-plasma-from-locally-adapted-curraleiro-p%C3%A3-duro-bulls-bos-taurus-identifying-biomarkers-involved-in-sperm-physiology-in-endangered-animals-for-conservation-of-biodiversity
#18
E B Menezes, R V de Oliveira, M F van Tilburg, E A Barbosa, N V Nascimento, A L M C S Velho, F B Moreno, R A Moreira, A C O Monteiro-Moreira, G M C Carvalho, A F Ramos, E Memili, A A Moura
The present study was aimed at evaluating the seminal plasma proteins and sperm parameters of Curraleiro Pé-Duro bulls. Semen was collected from 10 bulls by electroejaculation, and sperm parameters were evaluated in fresh and frozen-thawed semen. Seminal plasma proteins were analyzed by 2-D SDS-PAGE and mass spectrophotometry. Tools in computational biology were used to generate bioinformatic knowledge and evaluate gene ontology, protein-protein interactions, phylogenetic trees and multiple sequence alignments...
May 29, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28615690/cathepsin-d-regulates-lipid-metabolism-in-murine-steatohepatitis
#19
Tom Houben, Yvonne Oligschlaeger, Tim Hendrikx, Albert V Bitorina, Sofie M A Walenbergh, Patrick J van Gorp, Marion J J Gijbels, Silvia Friedrichs, Jogchum Plat, Frank G Schaap, Dieter Lütjohann, Marten H Hofker, Ronit Shiri-Sverdlov
Due to the obesity epidemic, non-alcoholic steatohepatitis (NASH) is a prevalent liver disease, characterized by fat accumulation and inflammation of the liver. However, due to a lack of mechanistic insight, diagnostic and therapeutic options for NASH are poor. Recent evidence has indicated cathepsin D (CTSD), a lysosomal enzyme, as a marker for NASH. Here, we investigated the function of CTSD in NASH by using an in vivo and in vitro model. In addition to diminished hepatic inflammation, inhibition of CTSD activity dramatically improved lipid metabolism, as demonstrated by decreased plasma and liver levels of both cholesterol and triglycerides...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611989/expression-of-cathepsins-b-d-and-g-in-isocitrate-dehydrogenase-wildtype-glioblastoma
#20
Sabrina P Koh, Agadha C Wickremesekera, Helen D Brasch, Reginald Marsh, Swee T Tan, Tinte Itinteang
AIM: To investigate the expression of cathepsins B, D, and G, in relation to the cancer stem cell (CSC) subpopulations, we have previously characterized within isocitrate dehydogenase (IDH)-wildtype glioblastoma (IDHWGB). METHODS: 3,3-Diaminobezidine (DAB) immunohistochemical (IHC) staining for cathepsins B, D, and G, was performed on 4μm-thick formalin-fixed paraffin-embedded IDHWGB samples obtained from six patients. Two representative DHWGB samples from the original cohort of patients were selected for immunofluorescent (IF) IHC staining, to identify the localization of the cathepsins in relation to the CSC subpopulations...
2017: Frontiers in Surgery
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