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https://www.readbyqxmd.com/read/27926992/inherited-diseases-caused-by-mutations-in-cathepsin-protease-genes
#1
REVIEW
Stephanie Ketterer, Alejandro Gomez-Auli, Larissa E Hillebrand, Agnese Petrera, Anett Ketscher, Thomas Reinheckel
Lysosomal cathepsins are proteolytic enzymes increasingly recognized as prognostic markers and potential therapeutic targets in a variety of diseases. In those conditions the cathepsins are mostly overexpressed, thereby driving the respective pathogenic processes. Although less known, there are also diseases with a genetic deficiency of cathepsins. In fact, nowadays six out of the fifteen human proteases called "cathepsins" have been linked to inherited syndromes. However, only three of these syndromes are typical lysosomal storage diseases, while the others are apparently caused by defective cleavage of specific protein substrates...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27926929/functional-and-evolutionary-analyses-identify-proteolysis-as-a-general-mechanism-for-nlrp1-inflammasome-activation
#2
Joseph Chavarría-Smith, Patrick S Mitchell, Alvin M Ho, Matthew D Daugherty, Russell E Vance
Inflammasomes are cytosolic multi-protein complexes that initiate immune responses to infection by recruiting and activating the Caspase-1 protease. Human NLRP1 was the first protein shown to form an inflammasome, but its physiological mechanism of activation remains unknown. Recently, specific variants of mouse and rat NLRP1 were found to be activated upon N-terminal cleavage by the anthrax lethal factor protease. However, agonists for other NLRP1 variants, including human NLRP1, are not known, and it remains unclear if they are also activated by proteolysis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926762/association-of-arterial-and-lymph-node-inflammation-with-distinct-inflammatory-pathways-in-human-immunodeficiency-virus-infection
#3
Ahmed Tawakol, Amorina Ishai, Danny Li, Richard A P Takx, Sophia Hur, Yannick Kaiser, Miguel Pampaloni, Adam Rupert, Denise Hsu, Irini Sereti, Rémi Fromentin, Nicolas Chomont, Peter Ganz, Steven G Deeks, Priscilla Y Hsue
Importance: Human immunodeficiency virus (HIV) infection is associated with a high risk of cardiovascular disease and increased arterial inflammation. In HIV, inflammation is also increased within lymph nodes (LNs), tissues known to harbor the virus even among treated and suppressed individuals. Objective: To test the hypothesis that arterial inflammation is linked to HIV disease activity and to inflammation within HIV-infected tissues (LNs). Design, Setting, and Participants: For this case-control study, participants were recruited from the SCOPE (Observational Study of the Consequences of the Protease Inhibitor Era) cohort, a clinic-based cohort of individuals receiving care at San Francisco General Hospital and the San Francisco Veteran's Affairs Medical Center...
December 7, 2016: JAMA Cardiology
https://www.readbyqxmd.com/read/27925497/anti-inflammatory-and-anticancer-effects-of-flavonol-glycosides-from-diplotaxis-harra-through-gsk3%C3%AE-regulation-in-intestinal-cells
#4
Imen Nasri, Rachid Chawech, Cynthia Girardi, Emmanuel Mas, Audrey Ferrand, Nathalie Vergnolle, Nicolas Fabre, Raoudha Mezghani-Jarraya, Claire Racaud-Sultan
CONTEXT AND OBJECTIVE: Diplotaxis harra (Forssk.) Boiss. (Brassicaceae) is traditionally used as an antidiabetic, anti-inflammatory or anticancer agent. In these pathologies, the glycogen synthase kinase 3 β (GSK3β) is overactivated and represents an interesting therapeutic target. Several flavonoids can inhibit GSK3β and the purpose of this study was to search for the compounds in Diplotaxis harra which are able to modulate GSK3β. MATERIALS AND METHODS: Methanol extracts from D...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27925396/arabidopsis-sumo-protease-asp1-positively-regulates-flowering-time-partially-through-regulating-flc-stability
#5
Xiangxiong Kong, Xi Luo, Gao-Ping Qu, Peng Liu, Jing Bo Jin
The initiation of flowering is tightly regulated by the endogenous and environment signals, which is crucial for the reproductive success of flowering plants. It is well known that autonomous and vernalization pathways repress transcription of FLOWERING LOCUS C (FLC), a focal floral repressor, but how its protein stability is regulated remains largely unknown. Here, we found that mutations in a novel Arabidopsis SUMO protease 1 (ASP1) resulted in a strong late-flowering phenotype under long-days, but to a lesser extent under short-days...
December 7, 2016: Journal of Integrative Plant Biology
https://www.readbyqxmd.com/read/27925362/ns5a-inhibitors-for-the-treatment-of-hepatitis-c-infection
#6
Stefano Gitto, Nesrine Gamal, Pietro Andreone
Today, we are witnessing a new era for the treatment of hepatitis C with excellent rates of virologic response and very good safety profiles. Among the many classes of direct acting antivirals, the inhibitors of non-structural protein 5A are particularly interesting. NS5A is phosphorylated protein with a relevant role in viral replication. HCV-NS5A inhibitors show high potency, very good safety profile and high barrier to resistance. The amazing in vitro effectiveness of this class is associated with great efficacy in clinical trials in combination protocols with antivirals of other classes, with sustained virological response (SVR) obtained in more than 90% of patients...
December 7, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27925197/factor-xa-signaling-contributes-to-the-pathogenesis-of-inflammatory-diseases
#7
REVIEW
Safieh Ebrahimi, Sara Rezaei, Parvaneh Seiri, Mikhail Ryzhikov, Seyed Issac Hashemy, Seyed Mahdi Hassanian
The coagulation protease Factor Xa (FXa) triggers a variety of signaling pathways through activation of protease-activated receptors (PARs) and non-PAR receptors. FXa-mediated signaling is strongly implicated in the pathogenesis of several inflammatory diseases including fibrosis, cardiovascular diseases and cancer. Thus, targeting of FXa can have great clinical significance in terms of the treatment of these disorders. This review summarizes the current knowledge about the mechanism of FXa signaling in cellular and animal systems under (patho)physiological conditions for a better understanding and hence a better management of FXa-induced disorders...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27925159/lectin-complement-pathway-proteins-in-healthy-individuals
#8
Anne Troldborg, Annette Hansen, Søren W K Hansen, Jens Christian Jensenius, Kristian Stengaard-Pedersen, Steffen Thiel
Since the discovery of the lectin pathway of complement activation, numerous clinical cohorts have been examined for one or more of the proteins, with the intention of uncovering the functions of the proteins or with the aim of discovering new biomarkers or diagnostic tools. To unveil the abnormal, it is pivotal to know the normal. Our aim was to describe the concentrations of the eleven known proteins of the lectin pathway in serum and plasma and to uncover possible gender differences, age and diurnal variations, which must be taken into account for investigations in different cohorts...
December 7, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27924123/increased-oxidative-stress-lipid-peroxidation-and-protein-degradation-trigger-senescence-in-iris-versicolor-l-flowers
#9
Syed Sabhi Ahmad, Inayatullah Tahir
Dynamics in various physiological and biochemical aspects were studied during various stages (I-tight bud stage to VI-senescent stage) of flower development in Iris versicolor. Floral diameter, fresh & dry mass and water content increased during flower opening and decreased towards senescence. Senescence was found to be related to the increased lipid peroxidation which was reflected in the decreased membrane stability index towards senescence. This increase in the lipid peroxidation was probably initiated by increased lipoxygenase activity which shot up just prior to the increase in lipid peroxidation...
October 2016: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
https://www.readbyqxmd.com/read/27924120/hippophae-rhamnoides-n-glycoproteome-analysis-a-small-step-towards-sea-buckthorn-proteome-mining
#10
Yaiphabi Sougrakpam, Renu Deswal
Hippophae rhamnoides is a hardy shrub capable of growing under extreme environmental conditions namely, high salt, drought and cold. Its ability to grow under extreme conditions and its wide application in pharmaceutical and nutraceutical industry calls for its in-depth analysis. N-glycoproteome mining by con A affinity chromatography from seedling was attempted. The glycoproteome was resolved on first and second dimension gel electrophoresis. A total of 48 spots were detected and 10 non-redundant proteins were identified by MALDI-TOF/TOF...
October 2016: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
https://www.readbyqxmd.com/read/27924117/transcriptome-differences-between-fiber-type-and-seed-type-cannabis-sativa-variety-exposed-to-salinity
#11
Jiajia Liu, Qin Qiao, Xia Cheng, Guanghui Du, Gang Deng, Mingzhi Zhao, Feihu Liu
The industrial hemp varieties 'Yunma 5' and 'Bamahuoma,' which demonstrate growth vigor and environmental adaptability, have been primarily cultivated in Yunnan and Guangxi, China, respectively, for fiber and seeds. The results of physiological measurements showed the phenotypic differences between the two varieties in response to salt stress. RNA-Seq analysis was first performed on leaves of both varieties sampled at four time intervals (0, 2, 4, 6 days) after treatment with salt (500 mM NaCl) We identified 220 co-up-regulated differentially expressed genes (DEGs) in the two varieties, while 26 up-regulated DEGs and 24 down-regulated DEGs were identified exclusively in the single varieties after 2 days of salt stress...
October 2016: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
https://www.readbyqxmd.com/read/27923946/prevalence-of-antiretroviral-drug-resistance-in-patients-who-are-not-responding-to-protease-inhibitor-based-treatment-results-from-the-first-national-survey-in-south-africa
#12
K Steegen, M Bronze, M A Papathanasopoulos, G van Zyl, D Goedhals, C Van Vuuren, W Macleod, I Sanne, W S Stevens, S C Carmona
Limited data exist on human immunodeficiency virus type 1 (HIV-1) resistance in patients who are not responding to protease inhibitor (PI)-based regimens in resource-limited settings. This study assessed resistance profiles in adults across South Africa who were not responding to PI-based regimens. pol sequencing was undertaken and submitted to the Stanford HIV Drug Resistance Database. At least 1 major PI mutation was detected in 16.4% of 350 participants. A total of 53.4% showed intermediate resistance to darunavir/ritonavir, whereas high-level resistance was not observed...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27923812/an-l-to-d-amino-acid-conversion-in-the-cell-penetrating-peptide-dftat-influences-proteolytic-stability-endocytic-uptake-and-endosomal-escape
#13
Kristina Najjar, Alfredo Erazo-Oliveras, Dakota J Brock, Ting-Yi Wang, Jean-Philippe Pellois
Cell-penetrating peptides (CPPs) are well established as delivery agents for otherwise cell-impermeable cargos. CPPs can also theoretically be used to modulate intracellular processes. However, their susceptibility to proteolytic degradation often limits their utility in these applications. Previous studies have explored the consequences on cellular uptake of converting the residues in CPPs from L to D stereochemistry, but conflicting results have been reported and specific steps en route to intracellular activity have not been explored...
December 6, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27923710/trypsin-and-n-aminopeptidase-apn-activities-in-the-hepatopancreas-of-an-intertidal-euryhaline-crab-biochemical-characteristics-and-differential-modulation-by-histamine-and-salinity
#14
Maria Soledad Michiels, Juana Cristina Del Valle, Alejandra A López Mañanes
No studies are available about biochemical characteristics and modulation (i.e. by endogenous and/or environmental cues) of trypsin (a key digestive endoprotease) in hepatopancreas of intertidal euryhaline crabs neither on the possible concomitant modulation of key ectoproteases such as aminopeptidase-N (APN) involved in final steps of protein digestion. Furthermore, nothing is still known in decapods crustaceans about the role of histamine as primary chemical messenger for modulation of main components of digestive process (i...
December 3, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27923620/fluorescent-diphenylphosphonate-based-probes-for-detection-of-serine-protease-activity-during-inflammation
#15
Laura E Edgington-Mitchell, Nicholas Barlow, Luigi Aurelio, Aminath Samha, Monika Szabo, Bim Graham, Nigel Bunnett
Activity-based probes are small molecules that covalently bind to the active site of a protease in an activity-dependent manner. We synthesized and characterized two fluorescent activity-based probes that target serine proteases with trypsin-like or elastase-like activity. We assessed the selectivity and potency of these probes against recombinant enzymes and demonstrated that while they are efficacious at labeling active proteases in complex protein mixtures in vitro, they are less valuable for in vivo studies...
November 25, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27923605/rhodomyrtone-inhibits-lipase-production-biofilm-formation-and-disorganizes-established-biofilm-in-propionibacterium-acnes
#16
Suttiwan Wunnoo, Jongkon Saising, Supayang Piyawan Voravuthikunchai
Virulence enzymes and biofilm a play crucial role in the pathogenesis of Propionibacterium acnes, a major causative agent of acne vulgaris. In the present study, the effects of rhodomyrtone, a pure compound identified from Rhodomyrtus tomentosa (Aiton) Hassk. leaves extract against enzyme production and biofilm formation production by 5 clinical isolates and a reference strain were evaluated. The degree of hydrolysis by both lipase and protease enzymes significantly decreased upon treatment with the compound at 0...
December 3, 2016: Anaerobe
https://www.readbyqxmd.com/read/27923568/noradrenaline-induces-cx3cl1-production-and-release-by-neurons
#17
José L M Madrigal, Javier R Caso, Borja García-Bueno, Irene L Gutiérrez, Juan C Leza
CX3CL1 is a chemokine for which neurons constitute its primary source within the brain. Besides acting as a chemokine, CX3CL1 regulates multiple processes and is known to inhibit microglial activation. Because of this, CX3CL1 is considered as a messenger used by neurons to communicate with microglia. Similarly, the neurotransmitter noradrenaline reduces microglial activation and production of neurotoxic agents. Based on this, the regulation of neuronal CX3CXL1 by noradrenaline was analyzed. In primary cortical neurons, noradrenaline induced the accumulation of CX3CL1 protein and mRNA...
December 3, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27923398/comparative-transcriptional-profile-of-the-fish-parasite-cryptocaryon-irritans
#18
Ze-Quan Mo, Yan-Wei Li, Hai-Qing Wang, Jiu-Le Wang, Lu-Yun Ni, Man Yang, Guo-Feng Lao, Xiao-Chun Luo, An-Xing Li, Xue-Ming Dan
BACKGROUND: Cryptocaryon irritans is an obligate ectoparasitic ciliate pathogen of marine fishes. It can infect most marine teleosts and cause heavy economic losses in aquaculture. There is currently no effective method of controlling this disease, and little information is available regarding the genes involved in its development and virulence. We aimed to investigate the distinct features of the three major life-cycle stages of C. irritans in terms of gene transcription level, and identify candidate vaccines/drug targets...
December 7, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27923176/co-distribution-of-cysteine-cathepsins-and-matrix-metalloproteases-in-human-dentin
#19
Polliana Mendes Candia Scaffa, Lorenzo Breschi, Annalisa Mazzoni, Cristina de Mattos Pimenta Vidal, Rosa Curci, Fabianni Apolonio, Pietro Gobbi, David Pashley, Leo Tjäderhane, Ivarne Luis Dos Santos Tersariol, Fábio Dupart Nascimento, Marcela Rocha Carrilho
It has been hypothesized that cysteine cathepsins (CTs) along with matrix metalloproteases (MMPs) may work in conjunction in the proteolysis of mature dentin matrix. The aim of this study was to verify simultaneously the distribution and presence of cathepsins B (CT-B) and K (CT-K) in partially demineralized dentin; and further to evaluate the activity of CTs and MMPs in the same tissue. The distribution of CT-B and CT-K in sound human dentin was assessed by immunohistochemistry. A double-immunolabeling technique was used to identify, at once, the occurrence of those enzymes in dentin...
November 21, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/27922627/blood-based-and-urinary-prostate-cancer-biomarkers-a-review-and-comparison-of-novel-biomarkers-for-detection-and-treatment-decisions
#20
REVIEW
R J Hendriks, I M van Oort, J A Schalken
BACKGROUND: The diagnosis of prostate cancer (PCa) is currently based on serum PSA testing and/or abnormal digital rectal examination and histopathologic evaluation of prostate biopsies. The main drawback of PSA testing is the lack of specificity for PCa. To improve early detection of PCa more specific biomarkers are needed. In the past few years, many new promising biomarkers have been identified; however, to date, only a few have reached clinical practice. METHODS: In this review, we discuss new blood-based and urinary biomarker models that are promising for usage in PCa detection, follow-up and treatment decision-making...
December 6, 2016: Prostate Cancer and Prostatic Diseases
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