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https://www.readbyqxmd.com/read/28545251/oxidative-stress-promoter-of-allergic-sensitization-to-protease-allergens
#1
REVIEW
Leonie S van Rijt, Lara Utsch, René Lutter, Ronald van Ree
Allergies arise from aberrant T helper type 2 responses to allergens. Several respiratory allergens possess proteolytic activity, which has been recognized to act as an adjuvant for the development of a Th2 response. Allergen source-derived proteases can activate the protease-activated receptor-2, have specific effects on immune cells by cleaving cell membrane-bound regulatory molecules, and can disrupt tight junctions. The protease activity can induce a non-allergen-specific inflammatory response in the airways, which will set the stage for an allergen-specific Th2 response...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28545186/gallium-nanoparticle-mediated-reduction-of-brain-specific-serine-protease-4-in-an-experimental-metastatic-cancer-model
#2
Enas M Moustafa, Marwa Abdelhameed Mohamed, Noura M Thabet
Purpose: Tumor growth and metastasis depend on angiogenesis; therefore, efforts are being made to develop specific angiogenic inhibitors. Gallium (Ga) is the second most common metal ion, after platinum, used in cancer treatment. Its activities are numerous and various. In the present study, we aimed to investigate the effect of Ga on brain metastasis arising from hepatocellular carcinoma (HCC). Materials and methods: Forty experimental rats (divided into 4 groups) received diethylnitrosamine (DEN) at a dose (20 mg/kg...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28545045/differences-in-speb-protease-activity-among-group-a-streptococci-associated-with-superficial-invasive-and-autoimmune-disease
#3
Anhphan T Ly, John P Noto, Odaelys L Walwyn, Robert R Tanz, Stanford T Shulman, William Kabat, Debra E Bessen
The secreted cysteine proteinase SpeB is an important virulence factor of group A streptococci (GAS), whereby SpeB activity varies widely among strains. To establish the degree to which SpeB activity correlates with disease, GAS organisms were recovered from patients with pharyngitis, impetigo, invasive disease or acute rheumatic fever (ARF), and selected for analysis using rigorous sampling criteria; >300 GAS isolates were tested for SpeB activity by casein digestion assays, and each GAS isolate was scored as a SpeB-producer or non-producer...
2017: PloS One
https://www.readbyqxmd.com/read/28544872/analysis-of-the-igf-system-in-milk-from-farm-animals-occurrence-regulation-and-biomarker-potential
#4
REVIEW
Zianka Meyer, Christine Höflich, Elisa Wirthgen, Sven Olm, Harald M Hammon, Andreas Hoeflich
IGFs and IGF-binding proteins (IGFBPs) are abundantly present in milk and in dairy products. Compared to the IGFs, the IGFBP have received less attention in milk, although truncated IGFBPs and IGFBP-glycosylation have been described in milk. Thereby, complex control of local IGF-effects can be assumed on the levels of IGFBPs, proteases, and protease inhibitors. The present review collects the current knowledge both on presence and regulation of IGFs and IGFBPs in milk particularly from dairy animal species...
May 12, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/28544703/high-ubiquitin-specific-protease-44-expression-induces-dna-aneuploidy-and-provides-independent-prognostic-information-in-gastric-cancer
#5
Sho Nishimura, Eiji Oki, Koji Ando, Makoto Iimori, Yu Nakaji, Yuichiro Nakashima, Hiroshi Saeki, Yoshinao Oda, Yoshihiko Maehara
Chromosomal instability (CIN), characterized by aneuploidy, is a major molecular subtype of gastric cancer. The deubiquitinase USP44 is an important regulator of APC activation in the spindle checkpoint and leads to proper chromosome separation to prevent aneuploidy. Aberrant expression of USP44 leads CIN in cells; however, the correlation between USP44 and DNA aneuploidy in gastric cancer is largely unknown. We analyzed USP44 expression in 207 patients with gastric cancer by immunohistochemistry and found that the proportion of USP44 expression was higher in gastric cancer tumors (mean, 39...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28544544/insulin-like-growth-factor-1-signaling-is-responsible-for-cathepsin-g-induced-aggregation-of-breast-cancer-mcf-7-cells
#6
Riyo Morimoto-Kamata, Satoru Yui
Cathepsin G (CG), a neutrophil serine protease, induces cell migration and multicellular aggregation of human breast cancer MCF-7 cells in a process that is dependent on E-cadherin and CG enzymatic activity. While these tumor cell aggregates can cause tumor emboli that could represent intravascular growth and extravasation into the surrounding tissues, resulting in metastasis, the molecular mechanism underlying this process remains poorly characterized. In this study, we aimed to identify the signaling pathway that is triggered during CG-mediated stimulation of cell aggregation...
May 24, 2017: Cancer Science
https://www.readbyqxmd.com/read/28544403/serine-protease-inhibitor-kazal-type-1-spink1-downregulates-e-cadherin-and-induces-emt-of-hepatoma-cells-to-promote-hepatocellular-carcinoma-metastasis-via-the-mek-erk-signaling-pathway
#7
Ying Hai-Yan, Gong Chao-Jie, Feng Yi, Jing Da-Dao, Lun-Gen Lu
OBJECTIVE: To investigate serine protease inhibitor Kazal type 1(SPINK1) expression and its influence on the prognosis of human hepatocellular carcinoma(HCC) and to explore the underlying molecular mechanisms involved. METHODS: Eighty patients with HCC who underwent curative resection were followed-up with a median observation time of 58.6 months.SPINK1expression was detected in the primary HCC samples by immunohistochemistry . Its role in tumor invasion and metastasis was evaluated in vitro by gene silence using siRNA-mediated approach, rSPINK1 and U0126(an inhibitor of MEK/ERK)...
May 23, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28544031/ubiquitin-specific-protease-8-is-a-novel-prognostic-marker-in-early-stage-lung-adenocarcinoma
#8
Yunjung Kim, Aya Shiba-Ishii, Tomoki Nakagawa, Ryan Edbert Husni, Shingo Sakashita, Tomoyo Takeuchi, Masayuki Noguchi
Alterations of epidermal growth factor receptor (EGFR) expression frequently occur in early-stage lung adenocarcinoma. Ubiquitin-specific protease 8 (USP8) has been reported to stabilize EGFR protein at the plasma membrane through the recycling pathway. Here, we examined the correlation between USP8 expression and the expression or mutation status of EGFR, as well as the clinicopathological features of lung adenocarcinoma and patient outcome. Expression of EGFR and USP8 in surgically resected specimens of lung adenocarcinoma (82 cases) was examined by immunohistochemistry...
May 19, 2017: Pathology International
https://www.readbyqxmd.com/read/28543088/3d-quantitative-structure-activity-relationship-and-docking-studies-of-coumarin-derivatives-as-tissue-kallikrein-7-inhibitors
#9
Xin Zheng, Mengxi He, Xiao Tan, Jun Zheng, Fangyu Wang, Sen Liu
OBJECTIVES: Kallikrein 7 (KLK7) is a secreted serine protease that plays important roles in skin desquamation and tumour progression, which makes it an attracting drug target. To guide the design of KLK7 inhibitors, a series of coumarin-based inhibitors were used to perform 3D-quantitative structure-activity relationship analysis. METHODS: 3D conformations of 37 inhibitors were generated and used to construct CoMFA and CoMSIA models. Then a complex model between the inhibitors and KLK7 was built with molecular docking...
May 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28542883/biochemical-characterization-and-dominance-of-different-hydrolases-in-different-types-of-daqu-a-chinese-industrial-fermentation-starter
#10
Jingjing Liu, Jingyu Chen, Yi Fan, Xiaoning Huang, Beizhong Han
BACKGROUND: Daqu is a fermentative saccharification agent that is used to initiate fermentation in the production of Chinese liquor and vinegar. This study investigated the differences of amylase, protease and esterase in dominance of different types of Daqu, which can be useful for quality control and flavor improvement of Daqu production by enzyme technology. RESULTS: Hydrolase activities in different Daqu samples were compared by Principal Component Analysis (PCA)...
May 25, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28542609/potent-and-selective-inhibition-of-pathogenic-viruses-by-engineered-ubiquitin-variants
#11
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/28542603/a-conformational-switch-high-throughput-screening-assay-and-allosteric-inhibition-of-the-flavivirus-ns2b-ns3-protease
#12
Matthew Brecher, Zhong Li, Binbin Liu, Jing Zhang, Cheri A Koetzner, Adham Alifarag, Susan A Jones, Qishan Lin, Laura D Kramer, Hongmin Li
The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC) to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors...
May 25, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28541760/inhibition-of-proteases-activity-in-intestine-needs-a-sustainable-acidic-environment-rather-than-a-transient
#13
Chang Xing, Jin-Feng Xing, Zhi-Qiang Ge
α-Chymotrypsin (α-CT) and trypsin are important components of the enzymatic barrier. They could degrade the therapeutic proteins and peptides, inhibit their activity consequently, and thereby reduce their oral bioavailability. Acidic agents, as one type of indirect protease inhibitors, have shown proof of concept in clinical trials. We report here the inactivated proteases due to acid influence can be reactivated immediately by environmental pH recovery regardless of how long the inactivation last. To keep the inactivation time of proteases for 4 to 5 h, we designed and prepared a sustained-release tablet containing citric acid (CA) which can effectively reduce the pH below 5...
May 25, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28541524/metal-bound-clamp-tag-inhibits-proteolytic-cleavage
#14
Michaela L McNiff, Jennifer S Chadwick
Biologics can be an improvement to small molecule drugs, providing high specificity for an identified target, lowering toxicity and limiting side effects. To achieve effective delivery, the biologic must have sufficient time to reach the target tissue. A prolonged half-life in the circulating environment is desired, but often serum stability is limited by proteases. Proteolysis in the serum causes degradation and inactivation as the biologic is fragmented and more rapidly cleared from the body. To improve the circulating half-life, large, hydrophilic polymers may be conjugated or stable fusion tags may be engineered to increase the effective size of the peptide and to hinder degradation by proteases...
May 25, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28541292/long-range-allosteric-regulation-of-the-human-26s-proteasome-by-20s-proteasome-targeting-cancer-drugs
#15
David Haselbach, Jil Schrader, Felix Lambrecht, Fabian Henneberg, Ashwin Chari, Holger Stark
The proteasome holoenzyme is the major non-lysosomal protease; its proteolytic activity is essential for cellular homeostasis. Thus, it is an attractive target for the development of chemotherapeutics. While the structural basis of core particle (CP) inhibitors is largely understood, their structural impact on the proteasome holoenzyme remains entirely elusive. Here, we determined the structure of the 26S proteasome with and without the inhibitor Oprozomib. Drug binding modifies the energy landscape of conformational motion in the proteasome regulatory particle (RP)...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28540665/different-molecular-mechanisms-mediate-direct-or-glia-dependent-prion-protein-fragment-90-231-neurotoxic-effects-in-cerebellar-granule-neurons
#16
Stefano Thellung, Elena Gatta, Francesca Pellistri, Valentina Villa, Alessandro Corsaro, Mario Nizzari, Mauro Robello, Tullio Florio
Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90-231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie (PrP(Sc)). PrP90-231 neurotoxicity is enhanced by the presence of microglia within neuronal culture, and associated to a rapid neuronal [Ca(++)] i increase...
May 25, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28540600/microglial-interferon-signaling-and-white-matter
#17
Ashley McDonough, Richard V Lee, Jonathan R Weinstein
Microglia, the resident immune cells of the CNS, are primary regulators of the neuroimmune response to injury. Type I interferons (IFNs), including the IFNαs and IFNβ, are key cytokines in the innate immune system. Their activity is implicated in the regulation of microglial function both during development and in response to neuroinflammation, ischemia, and neurodegeneration. Data from numerous studies in multiple sclerosis (MS) and stroke suggest that type I IFNs can modulate the microglial phenotype, influence the overall neuroimmune milieu, regulate phagocytosis, and affect blood-brain barrier integrity...
May 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28539977/human-immunodeficiency-virus-and-type-2-diabetes
#18
P Avari, S Devendra
The prevalence of diabetes is higher amongst individuals infected with HIV. The major contributor to hyperglycaemia is thought to be iatrogenic, with protease inhibitors being most commonly associated to insulin resistance. This article is to update general practitioners on the diagnosis and management of diabetes in HIV-infected patients. Specific considerations are highlighted including interactions of particular diabetic drugs with antiretroviral therapy (ART). We articulate why the use of Hemoglobin A1c (HbA1c) testing is not recommended as a diagnostic tool...
May 2017: London Journal of Primary Care
https://www.readbyqxmd.com/read/28539872/the-role-of-app-in-structural-spine-plasticity
#19
REVIEW
Elena Montagna, Mario M Dorostkar, Jochen Herms
Amyloid precursor protein (APP) is a transmembrane protein highly expressed in neurons. The full-length protein has cell-adhesion and receptor-like properties, which play roles in synapse formation and stability. Furthermore, APP can be cleaved by several proteases into numerous fragments, many of which affect synaptic function and stability. This review article focuses on the mechanisms of APP in structural spine plasticity, which encompasses the morphological alterations at excitatory synapses. These occur as changes in the number and morphology of dendritic spines, which correspond to the postsynaptic compartment of excitatory synapses...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28539755/practical-synthesis-of-the-bicyclic-darunavir-side-chain-3r-3as-6ar-hexahydrofuro-2-3-b-furan-3-ol-from-monopotassium-isocitrate
#20
REVIEW
Gary L Moore, Rodger W Stringham, David S Teager, Tai-Yuen Yue
A practical synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol-a key intermediate in the synthesis of darunavir-from monopotassium isocitrate is described. The isocitric acid salt, obtained from a high-yielding fermentation fed by sunflower oil, was converted in several steps to a tertiary amide. This amide, along with the compound's ester functionalities, was reduced with lithium aluminum hydride to give, on acidic workup, a transient aminal-triol. This was converted in situ to the title compound, the bicyclic acetal furofuranol side chain of darunavir, a protease inhibitor used in treatment of HIV/AIDS...
January 20, 2017: Organic Process Research & Development
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