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https://www.readbyqxmd.com/read/29352519/nafamostat-mesilate-attenuates-inflammation-and-apoptosis-and-promotes-locomotor-recovery-after-spinal-cord-injury
#1
Hui-Quan Duan, Qiu-Li Wu, Xue Yao, Bao-You Fan, Hong-Yu Shi, Chen-Xi Zhao, Yan Zhang, Bo Li, Chao Sun, Xiao-Hong Kong, Xin-Fu Zhou, Shi-Qing Feng
AIM: Spinal cord injury (SCI) leads to severe neural damage for which there is currently no effective treatment. Exploration of the neuroprotective effect among clinically approved drugs will speed up clinical translation of SCI. Nafamostat mesilate (NM) as a synthetic serine protease inhibitor has been used clinically in pancreatitis treatments. However, its effectiveness in SCI is unknown. The aim of this study was to confirm the efficacy of NM in ameliorating SCI. METHODS: Intraperitoneal administration of NM was performed on a contusion SCI model in Wistar rat...
January 19, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29352269/phosphorylation-by-protein-kinase-a-disassembles-the-caspase-9-core
#2
Banyuhay P Serrano, Jeanne A Hardy
Caspases, the cysteine proteases which facilitate the faithful execution of apoptosis, are tightly regulated by a number of mechanisms including phosphorylation. In response to cAMP, PKA phosphorylates caspase-9 at three sites preventing caspase-9 activation, and suppressing apoptosis progression. Phosphorylation of caspase-9 by PKA at the functionally relevant site Ser-183 acts as an upstream block of the apoptotic cascade, directly inactivating caspase-9 by a two-stage mechanism. First, Ser-183 phosphorylation prevents caspase-9 self-processing and directly blocks substrate binding...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352267/differential-susceptibility-of-striatal-hippocampal-and-cortical-neurons-to-caspase-6
#3
Anastasia Noël, Libin Zhou, Bénédicte Foveau, P Jesper Sjöström, Andréa C LeBlanc
Active cysteinyl protease Caspase-6 is associated with early Alzheimer and Huntington diseases. Higher entorhinal cortex and hippocampal Caspase-6 levels correlate with lower cognitive performance in aged humans. Caspase-6 induces axonal degeneration in human primary neuron cultures and causes inflammation and neurodegeneration in mouse hippocampus, and age-dependent memory impairment. To assess whether Caspase-6 causes damage to another neuronal system, a transgenic knock-in mouse overexpressing a self-activated form of Caspase-6 five-fold in the striatum, the area affected in Huntington disease, and 2...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352108/desumoylation-of-mkk7-kinase-by-the-sumo2-3-protease-senp3-potentiates-lipopolysaccharide-induced-inflammatory-signaling-in-macrophages
#4
Yimin Lao, Kai Yang, Zhaojun Wang, Xueqing Sun, Qiang Zou, Xiaoyan Yu, Jinke Cheng, Xuemei Tong, Edward Th Yeh, Jie Yang, Jing Yi
Protein SUMOylation has been reported to play a role in innate immune response, but the enzymes, substrates, and consequences of the specific inflammatory signaling events are largely unknown. Reactive oxygen species (ROS) are abundantly produced during macrophage activation and required for Toll-like receptor 4 (TLR4)-mediated inflammatory signaling. Previously, we demonstrated that SENP3 is a redox-sensitive SUMO2/3 protease. To explore any links between reversible SUMOylation and ROS-related inflammatory signaling in macrophage activation, we generated mice with SENP3 conditional knockout in myeloid cells...
January 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29351565/sumo-targeting-of-a-stress-tolerant-ulp1-sumo-protease
#5
Jennifer Peek, Catherine Harvey, Dreux Gray, Danny Rosenberg, Likhitha Kolla, Reuben Levy-Myers, Rui Yin, Jonathan L McMurry, Oliver Kerscher
SUMO proteases of the SENP/Ulp family are master regulators of both sumoylation and desumoylation and regulate SUMO homeostasis in eukaryotic cells. SUMO conjugates rapidly increase in response to cellular stress, including nutrient starvation, hypoxia, osmotic stress, DNA damage, heat shock, and other proteotoxic stressors. Nevertheless, little is known about the regulation and targeting of SUMO proteases during stress. To this end we have undertaken a detailed comparison of the SUMO-binding activity of the budding yeast protein Ulp1 (ScUlp1) and its ortholog in the thermotolerant yeast Kluyveromyces marxianus, KmUlp1...
2018: PloS One
https://www.readbyqxmd.com/read/29351561/preconception-use-of-cart-by-hiv-positive-pregnant-women-increases-the-risk-of-infants-being-born-small-for-gestational-age
#6
Ingrid J M Snijdewind, Colette Smit, Mieke H Godfried, Rachel Bakker, Jeannine F J B Nellen, Vincent W V Jaddoe, Elisabeth van Leeuwen, Peter Reiss, Eric A P Steegers, Marchina E van der Ende
BACKGROUND: The benefits of combination anti-retroviral therapy (cART) in HIV-positive pregnant women (improved maternal health and prevention of mother to child transmission [pMTCT]) currently outweigh the adverse effects due to cART. As the variety of cART increases, however, the question arises as to which type of cART is safest for pregnant women and women of childbearing age. We studied the effect of timing and exposure to different classes of cART on adverse birth outcomes in a large HIV cohort in the Netherlands...
2018: PloS One
https://www.readbyqxmd.com/read/29351202/antimicrobial-peptides-diversity-mechanism-of-action-and-strategies-to-improve-the-activity-and-biocompatibility-in-vivo
#7
REVIEW
Prashant Kumar, Jayachandran N Kizhakkedathu, Suzana K Straus
Antibiotic resistance is projected as one of the greatest threats to human health in the future and hence alternatives are being explored to combat resistance. Antimicrobial peptides (AMPs) have shown great promise, because use of AMPs leads bacteria to develop no or low resistance. In this review, we discuss the diversity, history and the various mechanisms of action of AMPs. Although many AMPs have reached clinical trials, to date not many have been approved by the US Food and Drug Administration (FDA) due to issues with toxicity, protease cleavage and short half-life...
January 19, 2018: Biomolecules
https://www.readbyqxmd.com/read/29350402/effectiveness-and-safety-of-original-and-generic-sofosbuvir-for-the-treatment-of-chronic-hepatitis-c-a-real-world-study
#8
Sebastián Marciano, Leila Haddad, María Virginia Reggiardo, Mirta Peralta, Cecilia Vistarini, Mónica Marino, Valeria Inés Descalzi, Claudia D'Amico, Sebastián Figueroa Escuti, Luis Alejandro Gaite, Roberto Pérez Ravier, Cristina Longo, Silvia Mabel Borzi, Omar Andrés Galdame, Fernando Bessone, Hugo Alberto Fainboim, Silvia Frías, Mariano Cartier, Adrián Carlos Gadano
We report the first real-world prospective multicenter cohort study that evaluated the effectiveness and safety of original or generic sofosbuvir-based regimens in patients with chronic hepatitis C in Latin America. The main endpoints were assessment of sustained virological response and serious adverse events rates. A total of 321 patients with chronic hepatitis C treated with the following regimens were included: sofosbuvir plus daclatasvir for 12 (n = 34) or 24 (n = 135) weeks, sofosbuvir plus daclatasvir plus ribavirin for 12 (n = 84) or 24 (n = 56) weeks, or sofosbuvir plus ribavirin for 12 (n = 8) or 24 (n = 2) weeks...
January 19, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29350293/diversity-and-enzymatic-potentialities-of-bacillus-sp-strains-isolated-from-a-polluted-freshwater-ecosystem-in-cuba
#9
Jeny Adina Larrea-Murrell, Marcia Maria Rojas-Badia, Ivette García-Soto, Beatriz Romeu-Alvarez, Tristano Bacchetti, Annika Gillis, Ana Karina Boltes-Espinola, Mayra Heydrich-Perez, Daysi Lugo-Moya, Jacques Mahillon
Genotypic and phenotypic characterization of Bacillus spp. from polluted freshwater has been poorly addressed. The objective of this research was to determine the diversity and enzymatic potentialities of Bacillus spp. strains isolated from the Almendares River. Bacilli strains from a polluted river were characterized by considering the production of extracellular enzymes using API ZYM. 14 strains were selected and identified using 16S rRNA, gyrB and aroE genes. Genotypic diversity of the Bacillus spp. strains was evaluated using pulsed field gel electrophoresis...
January 19, 2018: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29350268/the-epitope-mediated-mmp-activation-assay-detection-and-quantification-of-the-activation-of-mmp2-in-vivo-in-the-zebrafish-embryo
#10
Emma J Jeffrey, Bryan D Crawford
Matrix remodeling is a consequence of tightly regulated matrix metalloproteinase (MMP) activity. MMPs are synthesized as inactive precursors with auto-inhibitory N-terminal propeptides, the proteolytic removal of which exposes the catalytic zinc ion, rendering the protease active. The regulation of MMP activation has been investigated primarily in tissue culture and biochemical assays that lack important biological context. Here we present the epitope-mediated MMP activation (EMMA) assay and use it to observe the activation of Mmp2 (gelatinase A) by endogenous mechanisms in the intact zebrafish embryo...
January 19, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29349851/clinical-and-molecular-implications-of-structural-changes-to-desmosomes-and-corneodesmosomes
#11
REVIEW
Akemi Ishida-Yamamoto, Satomi Igawa, Mari Kishibe, Masaru Honma
Desmosomes provide the main intercellular adhesive properties between epidermal keratinocytes. Their distribution becomes uneven in severe dermatitis, multiple allergies and metabolic wasting syndrome due to desmoglein 1 deficiency and the loss of intercellular adhesion or acantholysis. When keratinocytes differentiate from granular cells into cornified cells, desmosomes are transformed into corneodesmosomes and can provide stronger intercellular adhesion. Degradation of corneodesmosomes is a tightly regulated process involving a number of proteases and their inhibitors...
January 19, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29349619/1h-15n-and-13c-chemical-shift-assignments-of-the-micelle-immersed-fat-c-terminal-fatc-domains-of-the-human-protein-kinases-ataxia-telangiectasia-mutated-atm-and-dna-dependent-protein-kinase-catalytic-subunit-dna-pkcs-fused-to-the-b1-domain-of-streptococcal
#12
Munirah S Abd Rahim, Lisa A M Sommer, Anja Wacker, Martin Schaad, Sonja A Dames
FAT C-terminal (FATC) is a circa 33 residue-long domain. It controls the kinase functionality in phosphatidylinositol-3 kinase-related kinases (PIKKs). Recent NMR- and CD-monitored interaction studies indicated that the FATC domains of all PIKKs can interact with membrane mimetics albeit with different preferences for membrane properties such as surface charge and curvature. Thus they may generally act as membrane anchoring unit. Here, we present the 1H, 15N, and 13C chemical shift assignments of the DPC micelle immersed FATC domains of the human PIKKs ataxia-telangiectasia mutated (ATM, residues 3024-3056) and DNA protein kinase catalytic subunit (DNA-PKcs, residues 4096-4128), both fused to the 56 residue long B1 domain of Streptococcal protein G (GB1)...
January 18, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29349515/matrix-metalloproteinase-2-and-9-activity-levels-increase-in-cutaneous-lupus-erythematosus-lesions-and-correlate-with-disease-severity
#13
Goksen Ertugrul, Didem Keles, Gulgun Oktay, Sebnem Aktan
Lupus erythematosus is a chronic autoimmune disease characterized by remissions and exacerbations. Accumulated evidence indicated that matrix metalloproteinases (MMPs) are upregulated in inflammatory cells of cutaneous lupus erythematosus (CLE); however, the activity levels of these proteases have remained uncharacterized. To elucidate the significance of MMP-2, MMP-9, and TIMP-1 in CLE pathogenesis, gelatin zymography was used to investigate pro and active levels of MMP-2 and MMP-9 in lesional and perilesional skin biopsies obtained from twenty-two CLE patients...
January 18, 2018: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29349092/cathepsin-b-plays-a-key-role-in-optimal-production-of-the-influenza-a-virus
#14
Macon D Coleman, Soon-Duck Ha, S M Mansour Haeryfar, Stephen Dominic Barr, Sung Ouk Kim
Background: Influenza A virus (IAV) is the etiologic agent of the febrile respiratory illness, commonly referred to as 'flu'. The lysosomal protease cathepsin B (CTSB) has shown to be involved in the lifecycle of various viruses. Here, we examined the role of CTSB in the IAV lifecycle. Methods: CTSB-deficient (CTSB-/-) macrophages and the human lung epithelial cell line A549 cells treated with CA-074Me were infected with the A/Puerto Rico/8/34 strain of IAV (IAV-PR8)...
2018: Journal of Virology & Antiviral Research
https://www.readbyqxmd.com/read/29349044/evaluating-the-effect-of-enzymatic-pretreatment-on-the-anaerobic-digestibility-of-pulp-and-paper-biosludge
#15
Sofia Bonilla, Zahra Choolaei, Torsten Meyer, Elizabeth A Edwards, Alexander F Yakunin, D Grant Allen
Anaerobic digestion of biosludge has not yet been implemented in pulp mills due to low biogas yields. Enzymatic pretreatment of biosludge has shown improvements in biogas yields but results are varied. A key limitation of previous studies is that they fail to consider the COD contribution from the enzyme solutions. The aim of this study was to systematically investigate the potential for enzymatic pretreatment on the anaerobic digestibility of pulp mill biosludge. Out of the six enzymes tested, four enhanced the anaerobic digestibility of biosludge...
March 2018: Biotechnology Reports
https://www.readbyqxmd.com/read/29348627/chikungunya-virus-nsp1-interacts-directly-with-nsp2-and-modulates-its-atpase-activity
#16
Sameer Kumar, Abhishek Kumar, Prabhudutta Mamidi, Atul Tiwari, Sriram Kumar, Animamalar Mayavannan, Sagarika Mudulli, Ajit Kumar Singh, Bharat Bhusan Subudhi, Soma Chattopadhyay
Chikungunya virus (CHIKV) is a mosquito-borne virus, which has created an alarming threat in the world due to unavailability of vaccine and antiviral compounds. The CHIKV nsP2 contains ATPase, RTPase, helicase and protease activities, whereas, nsP1 is a viral capping enzyme. In alphaviruses, the four non-structural proteins form the replication complex in the cytoplasm and this study characterizes the interaction between CHIKV nsP1 and nsP2. It was observed that, both the proteins co-localize in the cytoplasm and interact in the CHIKV infected cells by confocal microscopy and immunoprecipitation assay...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348584/quail-egg-homogenate-alleviates-food-allergy-induced-eosinophilic-esophagitis-like-disease-through-modulating-par-2-transduction-pathway-in-peanut-sensitized-mice
#17
Priscilia Lianto, Shiwen Han, Xinrui Li, Fredrick Onyango Ogutu, Yani Zhang, Zhuoyan Fan, Huilian Che
The present pharmacotherapy for eosinophilic esophagitis (EoE) fundamentally depend on inhaled corticosteroids. Despite the fact that oral intake of topical steroids can be successful in restricting EoE-related inflammation, there are concerns with respect to the long term utilization of steroids, especially in kids. In the current research, we assess the effect of quail egg, which is reportedly a known serine protease inhibitor, on symptomatology and immune responses in a peanut-sensitized mouse model of food allergy induced EoE...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348510/genome-and-secretome-analysis-of-pochonia-chlamydosporia-provide-new-insight-into-egg-parasitic-mechanisms
#18
Runmao Lin, Feifei Qin, Baoming Shen, Qianqian Shi, Chichuan Liu, Xi Zhang, Yang Jiao, Jun Lu, Yaoyao Gao, Marta Suarez-Fernandez, Federico Lopez-Moya, Luis Vicente Lopez-Llorca, Gang Wang, Zhenchuan Mao, Jian Ling, Yuhong Yang, Xinyue Cheng, Bingyan Xie
Pochonia chlamydosporia infects eggs and females of economically important plant-parasitic nematodes. The fungal isolates parasitizing different nematodes are genetically distinct. To understand their intraspecific genetic differentiation, parasitic mechanisms, and adaptive evolution, we assembled seven putative chromosomes of P. chlamydosporia strain 170 isolated from root-knot nematode eggs (~44 Mb, including 7.19% of transposable elements) and compared them with the genome of the strain 123 (~41 Mb) isolated from cereal cyst nematode...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348253/multifunctional-role-of-chymase-in-acute-and-chronic-tissue-injury-and-remodeling
#19
REVIEW
Louis J Dell'Italia, James F Collawn, Carlos M Ferrario
Chymase is the most efficient Ang II (angiotensin II)-forming enzyme in the human body and has been implicated in a wide variety of human diseases that also implicate its many other protease actions. Largely thought to be the product of mast cells, the identification of other cellular sources including cardiac fibroblasts and vascular endothelial cells demonstrates a more widely dispersed production and distribution system in various tissues. Furthermore, newly emerging evidence for its intracellular presence in cardiomyocytes and smooth muscle cells opens an entirely new compartment of chymase-mediated actions that were previously thought to be limited to the extracellular space...
January 19, 2018: Circulation Research
https://www.readbyqxmd.com/read/29348202/molecular-characterization-of-latent-gdf8-reveals-mechanisms-of-activation
#20
Ryan G Walker, Jason C McCoy, Magdalena Czepnik, Melanie J Mills, Adam Hagg, Kelly L Walton, Thomas R Cotton, Marko Hyvönen, Richard T Lee, Paul Gregorevic, Craig A Harrison, Thomas B Thompson
Growth/differentiation factor 8 (GDF8), or myostatin, negatively regulates muscle mass. GDF8 is held in a latent state through interactions with its N-terminal prodomain, much like TGF-β. Using a combination of small-angle X-ray scattering and mutagenesis, we characterized the interactions of GDF8 with its prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully latent state and an activated or "triggered" state where the prodomain remains in complex with the mature domain. However, these states are not reversible, indicating the latent GDF8 is "spring-loaded...
January 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
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