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https://www.readbyqxmd.com/read/29149696/clearance-of-plasmin-pn-1-complexes-by-vascular-smooth-muscle-cells-in-human-aneurysm-of-the-ascending-aorta
#1
Kamel Boukais, Luciano F Borges, Laurence Venisse, Ziad Touat, Déborah François, Véronique Arocas, Guillaume Jondeau, Paul Declerck, Marie-Christine Bouton, Jean-Baptiste Michel
Plasminogen is a circulating zymogen which enters the arterial wall by radial, transmural hydraulic conductance, where it is converted to plasmin by tissue plasminogen activator t-PA on an activation platform involving S100A4 on the vascular smooth muscle cell (vSMC) membrane. Plasmin is involved in the progression of human thoracic aneurysm of the ascending aorta (TAA). vSMCs protect the TAA wall from plasmin-induced proteolytic injury by expressing high levels of antiproteases. Protease nexin-1 (PN-1) is a tissue antiprotease belonging to the serpin superfamily, expressed in the vascular wall, and is able to form a covalent complex with plasmin...
October 24, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/29149631/prostaglandin-j2-promotes-o-glcnacylation-raising-app-processing-by-%C3%AE-and-%C3%AE-secretases-relevance-to-alzheimer-s-disease
#2
Teneka Jean-Louis, Patricia Rockwell, Maria E Figueiredo-Pereira
Regulation of the amyloid precursor protein (APP) processing by α- and β-secretases is of special interest to Alzheimer's disease (AD), as these proteases prevent or mediate amyloid beta formation, respectively. Neuroinflammation is also implicated in AD. Our data demonstrate that the endogenous mediator of inflammation prostaglandin J2 (PGJ2) promotes full-length APP (FL-APP) processing by α- and β-secretases. The decrease in FL-APP was independent of proteasomal, lysosomal, calpain, caspase, and γ-secretase activities...
November 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29149530/proteases-and-protease-inhibitors-in-infectious-diseases
#3
REVIEW
Ayodeji A Agbowuro, Wilhelmina M Huston, Allan B Gamble, Joel D A Tyndall
There are numerous proteases of pathogenic organisms that are currently targeted for therapeutic intervention along with many that are seen as potential drug targets. This review discusses the chemical and biological makeup of some key druggable proteases expressed by the five major classes of disease causing agents, namely bacteria, viruses, fungi, eukaryotes, and prions. While a few of these enzymes including HIV protease and HCV NS3-4A protease have been targeted to a clinically useful level, a number are yet to yield any clinical outcomes in terms of antimicrobial therapy...
November 17, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29148898/enhancement-of-invadopodia-activity-in-glioma-cells-by-sublethal-doses-of-irradiation-and-temozolomide
#4
Leon Mao, Clarissa A Whitehead, Lucia Paradiso, Andrew H Kaye, Andrew P Morokoff, Rodney B Luwor, Stanley S Stylli
OBJECTIVE Glioblastoma is the most common primary central nervous system tumor in adults. These tumors are highly invasive and infiltrative and result in tumor recurrence as well as an extremely poor patient prognosis. The current standard of care involves surgery, radiotherapy, and chemotherapy. However, previous studies have suggested that glioblastoma cells that survive treatment are potentially more invasive. The goal of this study was to investigate whether this increased phenotype in surviving cells is facilitated by actin-rich, membrane-based structures known as invadopodia...
November 17, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29148820/a-functional-kinase-short-interfering-ribonucleic-acid-screen-using-protease-activated-receptor-2-dependent-opening-of-transient-receptor-potential-vanilloid-4
#5
William G Darby, Megan S Grace, Kaylene J Simpson, Owen L Woodman, Peter McIntyre
Protease-activated receptor 2 (PAR2) is a proinflammatory G-protein coupled receptor (GPCR) that is activated by inflammatory proteases, and its activation initiates signaling pathways that modulate the nonselective cation channel transient receptor potential vanilloid-4 (TRPV4). PAR2-dependent opening of TRPV4 has been attributed to kinase activation, but the identity of the responsible enzymes is unknown. Deciphering the signaling pathways involved in the PAR2-dependent opening of TRPV4 may yield new targets for pain treatment...
November 17, 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29148558/ultrasound-propelled-nanowire-motors-enhance-asparaginase-enzymatic-activity-against-cancer-cells
#6
Murat Uygun, Beatriz Jurado-Sánchez, Deniz Aktas Uygun, Virendra Vikram Singh, Liangfang Zhang, Joseph Wang
Ultrasound-(US) propelled nanowires consisting of Au/Ni/Au/PEDOT-PPy-COOH segments are modified with asparaginase enzyme and applied as an effective anti-cancer agent. After immobilization of asparaginase onto the surface of the nanowire motors, the enzyme displays enhanced thermal and pH stabilities, improved resistance towards protease, and higher affinity for the substrate. The fast motion of the motor-carrying asparaginase leads to greatly accelerated biocatalytic depletion of asparagine and hence to a significantly enhanced inhibition efficacy against El4 lymphoma cancer cells (92%) as compared to free enzyme counterpart (17%) and other control groups...
November 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/29147970/effect-of-different-salinities-on-gene-expression-and-activity-of-digestive-enzymes-in-the-thick-lipped-grey-mullet-chelon-labrosus
#7
REVIEW
I M Pujante, F J Moyano, J A Martos-Sitcha, J M Mancera, G Martínez-Rodríguez
The effects of different environmental salinities (0, 12, 40, and 55 ppt) on pepsinogen 2 (pga2), trypsinogen 2 (try2), chymotrypsinogen (ctr), and pancreatic alpha-amylase (amy2a) gene expression, and on the total activities of their corresponding enzymes, were assessed in Chelon labrosus juveniles, after their corresponding full-complementary DNA sequences were cloned. Furthermore, the quantitative effect of different salinities on the hydrolysis of feed protein by fish digestive enzymes was evaluated using an in vitro system...
November 17, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/29147901/expression-of-dj-1-in-neurodegenerative-disorders
#8
Daria Antipova, Rina Bandopadhyay
In 2003, autosomal recessive loss-of-function mutations were identified in PARK7 gene that caused early-onset Parkinson's disease (PD). The PARK7 gene encodes a conserved protein termed DJ-1. DJ-1 is a ubiquitous protein, and within the brain, it is present in the nucleus and cytoplasm of both neuronal and glial cells. DJ-1 is a multifunctional protein, and numerous studies have ascribed various roles, including antioxidative properties, chaperone function, protease activities, mitochondrial functions and regulation of transcription to the protein...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147900/structural-biology-of-the-dj-1-superfamily
#9
Nathan Smith, Mark A Wilson
The DJ-1 (also called the DJ-1/PfpI, ThiJ/PfpI, or DJ-1/ThiJ/PfpI) superfamily is a structural and functional diverse group of proteins that are present in most organisms. Many of these proteins remain poorly characterized at the biochemical level, but include some known chaperones, proteases, and various stress response proteins that remain mechanistically mysterious. This chapter outlines what is known from a structural perspective about the cellular and biochemical functions of many of these proteins from distinct clades of the superfamily in several organisms...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147793/pharmacophoric-characteristics-of-dengue-virus-ns2b-ns3pro-inhibitors-a-systematic-review-of-the-most-promising-compounds
#10
REVIEW
Camyla Alves Leonel, William Gustavo Lima, Michelli Dos Santos, Ariane Coelho Ferraz, Alex Gutterres Taranto, José Carlos de Magalhães, Luciana Lara Dos Santos, Jaqueline Maria Siqueira Ferreira
Dengue virus (DENV) infection can lead to a wide range of clinical manifestations, including fatal hemorrhagic complications. There is a need to find effective pharmacotherapies to treat this disease due to the lack of specific immunotherapies and antiviral drugs. That said, the DENV NS2B/NS3pro protease complex is essential in both the viral multiplication cycle and in disease pathogenesis, and is considered a promising target for new antiviral therapies. Here, we performed a systematic review to evaluate the pharmacophoric characteristics of promising compounds against NS2B/NS3pro reported in the past 10 years...
November 16, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29147645/real-world-cure-rates-for-hepatitis-c-virus-treatments-that-include-simeprevir-and-or-sofosbuvir-are-comparable-to-clinical-trial-results
#11
Kian Bichoupan, Neeta Tandon, James F Crismale, Joshua Hartman, David Del Bello, Neal Patel, Sweta Chekuri, Alyson Harty, Michel Ng, Keith M Sigel, Meena B Bansal, Priya Grewal, Charissa Y Chang, Jennifer Leong, Gene Y Im, Lawrence U Liu, Joseph A Odin, Nancy Bach, Scott L Friedman, Thomas D Schiano, Ponni V Perumalswami, Douglas T Dieterich, Andrea D Branch
AIM: To assess the real-world effectiveness and cost of simeprevir (SMV), and/or sofosbuvir (SOF)-based therapy for chronic hepatitis C virus (HCV) infection. METHODS: The real-world performance of patients treated with SMV/SOF ± ribavirin (RBV), SOF/RBV, and SOF/RBV with pegylated-interferon (PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included...
November 12, 2017: World Journal of Virology
https://www.readbyqxmd.com/read/29147019/identification-and-characterization-of-serine-protease-inhibitors-in-a-parasitic-wasp-pteromalus-puparum
#12
Lei Yang, Yaotian Mei, Qi Fang, Jiale Wang, Zhichao Yan, Qisheng Song, Zhe Lin, Gongyin Ye
Serine protease inhibitors (SPIs) regulate protease-mediated activities by inactivating their cognate proteinases, and are involved in multiple physiological processes. SPIs have been extensively studied in vertebrates and invertebrates; however, little SPI information is available in parasitoids. Herein, we identified 57 SPI genes in total through the genome of a parasitoid wasp, Pteromalus puparum. Gene structure analyses revealed that these SPIs contain 7 SPI domains. Depending on their mode of action, these SPIs can be categorized into serpins, canonical inhibitors and alpha-2-macroglobulins (A2Ms)...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146927/preparation-and-functional-evaluation-of-collagen-oligopeptide-rich-hydrolysate-from-fish-skin-with-the-serine-collagenolytic-protease-from-pseudoalteromonas-sp-sm9913
#13
Xiu-Lan Chen, Ming Peng, Jing Li, Bai-Lu Tang, Xuan Shao, Fang Zhao, Chang Liu, Xi-Ying Zhang, Ping-Yi Li, Mei Shi, Yu-Zhong Zhang, Xiao-Yan Song
Although several serine collagenolytic proteases from bacteria were reported, none has been used to prepare bioactive collagen peptides. MCP-01 is the most abundant extracellular protease of deep-sea Pseudoalteromonas sp. SM9913 and is a serine collagenolytic protease with high efficiency on fish collagen hydrolysis. Here, we set up a pilot scale process to ferment SM9913 for extracellular protease production. With SM9913 extracellular protease as a tool, a process to prepare collagen oligopeptide-rich hydrolysate from codfish skin was set up, which was further scaled up to pilot (100 L) and plant (2000 L) levels with yields >66%...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146750/trpm7-transient-receptor-potential-melastatin-like-7-channel-kinase-controls-calcium-responses-in-arterial-thrombosis-and-stroke-in-mice
#14
Sanjeev K Gotru, Wenchun Chen, Peter Kraft, Isabelle C Becker, Karen Wolf, Simon Stritt, Susanna Zierler, Heike M Hermanns, Deviyani Rao, Anne-Laure Perraud, Carsten Schmitz, René P Zahedi, Peter J Noy, Michael G Tomlinson, Thomas Dandekar, Masayuki Matsushita, Vladimir Chubanov, Thomas Gudermann, Guido Stoll, Bernhard Nieswandt, Attila Braun
OBJECTIVE: TRPM7 (transient receptor potential melastatin-like 7 channel) is a ubiquitously expressed bifunctional protein comprising a transient receptor potential channel segment linked to a cytosolic α-type serine/threonine protein kinase domain. TRPM7 forms a constitutively active Mg(2+) and Ca(2+) permeable channel, which regulates diverse cellular processes in both healthy and diseased conditions, but the physiological role of TRPM7 kinase remains largely unknown. APPROACH AND RESULTS: Here we show that point mutation in TRPM7 kinase domain deleting the kinase activity in mice (Trpm7(R/R) ) causes a marked signaling defect in platelets...
November 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29146736/quantitative-high-throughput-screening-identifies-cytoprotective-molecules-that-enhance-sumo-conjugation-via-the-inhibition-of-sumo-specific-protease-senp-2
#15
Joshua D Bernstock, Daniel Ye, Jayden A Smith, Yang-Ja Lee, Florian A Gessler, Adam Yasgar, Jennifer Kouznetsova, Ajit Jadhav, Zhuoran Wang, Stefano Pluchino, Wei Zheng, Anton Simeonov, John M Hallenbeck, Wei Yang
The development of novel neuroprotective treatments for acute stroke has been fraught with failures, which supports the view of ischemic brain damage as a highly complex multifactorial process. Post-translational modifications such as small ubiquitin-like modifier (SUMO)ylation have emerged as critical molecular regulatory mechanisms in states of both homeostasis and ischemic stress, as evidenced by our previous work. Accordingly, the clinical significance of the selective control of the global SUMOylation process has become apparent in studies of ischemic pathobiology and pathophysiology...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146445/interplay-between-daily-rhythmic-serum-mediated-bacterial-killing-activity-and-immune-defence-factors-in-rainbow-trout-oncorhynchus-mykiss
#16
Carlo C Lazado, Manuel Gesto, Lone Madsen, Alfred Jokumsen
Circadian rhythm is emerging as an important regulator of immune functions. However, there is a paucity of information on the influence of this biological phenomenon in the antimicrobial factors in teleost fish. This study investigated the dynamics and interplay of serum-mediated bacterial killing activity and immune defence factors throughout the light:dark (LD) cycle in rainbow trout (Oncorhynchus mykiss). The juvenile fish came from two different emergence time fractions (i.e., late and early) that were believed to exhibit behavioural and physiological differences...
November 13, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29145807/durability-of-switch-regimens-based-on-rilpivirine-or-on-integrase-inhibitors-both-in-association-with-tenofovir-and-emtricitabine-in-hiv-infected-virologically-suppressed-patients
#17
Nicola Gianotti, Andrea Poli, Silvia Nozza, Laura Galli, Nadia Galizzi, Marco Ripa, Marco Merli, Alessia Carbone, Vincenzo Spagnuolo, Adriano Lazzarin, Antonella Castagna
BACKGROUND: Switch strategies based on rilpivirine/tenofovir/emtricitabine or on an integrase inhibitor (InSTI) plus tenofovir/emtricitabine have never been compared in randomized clinical trials. The main aim of the study was to investigate the durability of these two switch regimens in virologically suppressed, HIV-infected patients. METHODS: Retrospective analysis of patients who started rilpivirine or an InSTI (both with tenofovir and emtricitabine) with <50 HIV-RNA copies/mL and had at least one HIV-RNA assessed while receiving the study regimen...
November 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29145610/transition-to-an-aquatic-habitat-permitted-the-repeated-loss-of-the-pleiotropic-klk8-gene-in-mammals
#18
Nikolai Hecker, Virag Sharma, Michael Hiller
KLK8 (also called neuropsin) is a serine protease that plays distinct roles in the skin and hippocampus. In the skin, KLK8 influences keratinocyte proliferation and desquamation, and activates antimicrobial peptides in sweat. In the hippocampus, KLK8 affects memory acquisition. Here, we examined the evolution of KLK8 in mammals and discovered that, out of 70 placental mammals, KLK8 is exclusively lost in three independent fully-aquatic lineages, comprising dolphin, killer whale, minke whale and manatee. In addition, while the sperm whale has an intact KLK8 reading frame, the gene evolves neutrally in this species...
November 14, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29145514/why-patients-with-thbd-c-1611c-a-p-cys537x-nonsense-mutation-have-high-levels-of-soluble-thrombomodulin
#19
Yohann Jourdy, Nathalie Enjolras, Sandra Le Quellec, Jean Claude Bordet, Claude Négrier, Christine Vinciguerra, Yesim Dargaud
BACKGROUND: Recently our group has described a new autosomal dominant bleeding disorder characterized by very high plasma levels of soluble thrombomodulin (TM). The THBD c.1611C>A (p.Cys537X) mutation in heterozygous state was found in the propositus. This mutation leads to the synthesis of a truncated TM which has lost the last three amino-acids of the transmembrane domain and the cytoplasmic tail. OBJECTIVE: We investigated the mechanism responsible for TM shedding in endothelial cells with THBD c...
2017: PloS One
https://www.readbyqxmd.com/read/29145473/suppression-and-resolution-of-autoimmune-arthritis-by-rhesus-%C3%AE-defensin-1-an-immunomodulatory-macrocyclic-peptide
#20
Justin B Schaal, Dat Q Tran, Akshay Subramanian, Reshma Patel, Teresina Laragione, Kevin D Roberts, Katie Trinh, Prasad Tongaonkar, Patti A Tran, Dmitriy Minond, Gregg B Fields, Paul Beringer, André J Ouellette, Percio S Gulko, Michael E Selsted
θ-defensins constitute a family of macrocyclic peptides expressed exclusively in Old World monkeys. The peptides are pleiotropic effectors of innate immunity, possessing broad spectrum antimicrobial activities and immunoregulatory properties. Here we report that rhesus θ-defensin 1 (RTD-1) is highly effective in arresting and reversing joint disease in a rodent model of rheumatoid arthritis (RA). Parenteral RTD-1 treatment of DA/OlaHsd rats with established pristane-induced arthritis (PIA) rapidly suppressed joint disease progression, restored limb mobility, and preserved normal joint architecture...
2017: PloS One
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