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https://www.readbyqxmd.com/read/29775759/-938-rhrk-941-is-responsible-for-ubiquitin-specific-protease-48-nuclear-translocation-which-can-stabilize-nf-%C3%AE%C2%BAb-p65-in-the-nucleus
#1
Ying-Li Liu, Jing Yan, Jie Zheng, Qing-Bao Tian
The transcription factor NF-κB is a key regulator of cellular processes. A mechanism that contributes to timely termination of NF-κB activity is UPS-dependent degradation of p65 in the nucleus or on chromatin. The ubiquitin-specific protease that takes part in this process and its molecular mechanisms are shown in previous study, but which structural feature of USP48 was responsible for these effects is unknown. Here, we show that maybe the stability of NF-κB is controlled by proteasome-mediated degradation and ubiquitin-specific protease 48 (USP48), also known as synaptic ubiquitin-specific protease (synUSP) or USP31, can enhance NF-κB stability through proteasome-dependent regulation in the nucleus...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775725/anti-hepatitis-c-virus-activity-and-synergistic-effect-of-nymphaea-alba-extracts-and-bioactive-constituents-in-liver-infected-cells
#2
Sidra Rehman, Usman Ali Ashfaq, Bushra Ijaz, Sheikh Riazuddin
BACKGROUND: Without an effective vaccine, hepatitis C virus (HCV) remains a global threat, inflicting 170-300 million carriers worldwide at risk of cirrhosis and hepatocellular carcinoma (HCC). Though various direct acting antivirals have been redeemed the hepatitis C treatment, a few restraints persist including possible side effects, viral resistance emergence, excessive cost which restricts its availability to a common person. HYPOTHESIS: There is no preventive HCV vaccine available today so the discovery of potent antiviral natural flora and their bioactive constituents may help to develop preventive cures against HCV infection...
May 15, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29775399/dolutegravir-and-rilpivirine-for-the-maintenance-treatment-of-virologically-suppressed-hiv-1-infection
#3
Jose L Casado, Marta Monsalvo, Aurora M Rojo, María Fontecha, Miguel A Rodriguez-Sagrado
Triple combinations of antiretroviral (ART) drugs are the standard treatment for HIV infection, but the challenges include long-term side effects, high costs, and adherence. The recent advent of potent and well tolerated ART has renewed the interest for newer ART strategies. A dual regimen with the combination of dolutegravir (DTG) and rilpivirine (RPV), two well tolerated, metabolic-friendly, and potent drugs could offer additional benefits. Areas covered: A review of recent randomized trials and observational cohorts concerning the use of a dual therapy with DTG plus RPV as a switching strategy in patients with viral suppression...
May 18, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29775273/the-role-of-clpp-protease-in-bacterial-pathogenesis-and-human-diseases
#4
Vaibhav Bhandari, Keith S Wong, Jin Lin Zhou, Mark F Mabanglo, Robert A Batey, Walid A Houry
In prokaryotic cells and eukaryotic organelles, the ClpP protease plays an important role in proteostasis. The disruption of ClpP function has been shown to influence the infectivity and virulence of a number of bacterial pathogens. More recently, ClpP has been found to be involved in various forms of carcinomas and in Perrault syndrome, which is an inherited condition characterized by hearing loss in males and females and by ovarian abnormalities in females. Hence, targeting ClpP is a potentially viable, attractive option for the treatment of different ailments...
May 18, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29774097/natriuretic-peptides-system-in-the-pulmonary-tissue-of-rats-with-heart-failure-potential-involvement-in-lung-edema-and-inflammation
#5
Emad E Khoury, Safa Kinaneh, Doron Aronson, Offer Amir, Diab Ghanim, Natalia Volinsky, Zaher Azzam, Zaid Abassi
Congestive heart failure (CHF) often leads to progressive cardiac hypertrophy and salt/water retention as evident by peripheral and lung edema. Although the pathogenesis of CHF remains largely unclarified, it is widely accepted that neurohormonal changes and inflammatory processes are profoundly involved in structural and functional deterioration of vital organs including, heart, kidney and lungs. Corin, a cardiac serine protease, is responsible for converting pro-ANP and pro-BNP to biologically active natriuretic peptides (NPs)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774092/vorapaxar-treatment-reduces-mesangial-expansion-in-streptozotocin-induced-diabetic-nephropathy-in-mice
#6
Maaike Waasdorp, JanWillem Duitman, Sandrine Florquin, C Arnold Spek
Background: Twenty years after the onset of diabetes, up to 40% of patients develop diabetic nephropathy. Protease-activated receptor-1 (PAR-1) has recently been shown to aggravate the development of experimental diabetic nephropathy. PAR-1 deficient mice develop less albuminuria and glomerular lesions and PAR-1 stimulation induces proliferation and fibronectin production in mesangial cells in vitro . Vorapaxar is a clinically available PAR-1 inhibitor which is currently used for secondary prevention of ischemic events...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773933/prevalence-of-and-risk-factors-for-prediabetes-in-patients-infected-with-hiv
#7
Syed Arafath, Tavajay Campbell, Jameela Yusuff, Roopali Sharma
Background: The use of highly active antiretroviral therapy (HAART) has resulted in a dramatic decrease in morbidity and mortality in HIV-infected patients. Components of HAART (e.g., protease inhibitors and nucleoside reverse transcriptase inhibitors), as well as HIV infection itself, can have significant effects on developing new-onset diabetes. The goals of this study were to determine the prevalence of prediabetes and to assess risk factors associated with prediabetes in a cohort of HIV-infected patients...
May 2018: Diabetes Spectrum: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29773710/arginine-methylation-is-required-for-canonical-wnt-signaling-and-endolysosomal-trafficking
#8
Lauren V Albrecht, Diego Ploper, Nydia Tejeda-Muñoz, Edward M De Robertis
Arginine methylation has emerged as a widespread and reversible protein modification with the potential to regulate a multitude of cellular processes, but its function is poorly understood. Endolysosomes play an important role in Wnt signaling, in which glycogen synthase kinase 3 (GSK3) becomes sequestered inside multivesicular bodies (MVBs) by the process known as microautophagy, causing the stabilization of many proteins. Up to 20% of cellular proteins contain three or more consecutive putative GSK3 sites, and of these 33% also contain methylarginine (meArg) modifications...
May 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29773673/lysosomal-proteome-and-secretome-analysis-identifies-missorted-enzymes-and-their-non-degraded-substrates-in-mucolipidosis-iii-mouse-cells
#9
Giorgia Di Lorenzo, Renata Voltolini Velho, Dominic Winter, Melanie Thelen, Shiva Ahmadi, Michaela Schweizer, Raffaella De Pace, Kerstin Cornils, Timur Alexander Yorgan, Saskia Grüb, Irm Hermans-Borgmeyer, Thorsten Schinke, Sven Müller-Loennies, Thomas Braulke, Sandra Pohl
Targeting of soluble lysosomal enzymes requires mannose 6-phosphate (M6P) signals whose formation is initiated by the hexameric N-acetylglucosamine (GlcNAc)-1-phosphotransferase complex (α2β2γ2). Upon proteolytic cleavage by site-1 protease, the α/β-subunit precursor is catalytically activated but the functions of γ-subunits (Gnptg) in M6P modification of lysosomal enzymes are unknown. To investigate this, we analyzed the Gnptg expression in mouse tissues, primary cultured cells, and in Gnptg reporter mice in vivo, and found high amounts in the brain, eye, kidney, femur, vertebra and fibroblasts...
May 17, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29773651/usp25m-protease-regulates-ubiquitin-like-processing-of-tug-proteins-to-control-glut4-glucose-transporter-translocation-in-adipocytes
#10
Estifanos N Habtemichael, Don T Li, Abel Alcázar-Román, Xavier O Westergaard, Muyi Li, Max C Petersen, Hanbing Li, Stephen G DeVries, Eric Li, Omar Julca-Zevallos, Joseph S Wolenski, Jonathan S Bogan
Insulin stimulates the exocytic translocation of specialized vesicles in adipocytes, which inserts GLUT4 glucose transporters into the plasma membrane to enhance glucose uptake.  Previous results support a model in which TUG proteins trap these GLUT4 storage vesicles at the Golgi matrix, and in which insulin triggers endoproteolytic cleavage of TUG to translocate GLUT4.  Here, we identify Usp25m as a protease required for insulin-stimulated TUG cleavage and GLUT4 translocation in adipocytes.  Usp25m is expressed in adipocytes, binds TUG and GLUT4, dissociates from TUG-bound vesicles after insulin addition, and colocalizes with TUG and insulin-responsive cargoes in unstimulated cells...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29773143/sex-and-vaccination-insights-from-female-rats-vaccinated-with-juvenile-specific-proteases-from-fasciola-hepatica
#11
Agnieszka Wesołowska, Katarzyna Basałaj, Luke J Norbury, Alicja Sielicka, Halina Wędrychowicz, Anna Zawistowska-Deniziak
Most animal research is less evidence-based for females, with the majority of studies conducted on males. Since immune responses vary between males and females, sexual dimorphism in immunity contributes, among other things, to sex-based differences post-vaccination. However, the issue of sex effects in animal vaccine research is rarely considered in vaccine study design. Previously, we have evaluated the efficacy of cathepsin L3 (FhCL3-1 and FhCL3-2) and B3 proteases (FhCB3) from juvenile Fasciola hepatica as vaccines against fasciolosis in male rats...
May 15, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29772993/shoulder-lesion-in-a-69-year-old-woman
#12
Andrew J Hayden, Srinivas Kolla, Adele L Boskey, Steven Burekhovich, Chuanyong Lu, Michael Stracher, Aditya V Maheshwari
Milwaukee Shoulder Syndrome (MSS) is a painful progressive arthropathy in which hydroxyapatite crystal deposition in synovial tissue induces lysosomal release of collagenase and neutral proteases. These enzymes are destructive to periarticular tissue, including the synovium, articular cartilage, rotator cuff muscles, and the intrasynovial cortical bone. MSS predominantly occurring in women (90%) over the age of 70 years of age with a clinical history marked by recurrent joint effusions and pain, which classically worsens at night...
2018: Journal of Long-term Effects of Medical Implants
https://www.readbyqxmd.com/read/29772538/targeting-fibroblast-activation-protein-in-cancer-prospects-and-caveats
#13
Petr Busek, Rosana Mateu, Michal Zubal, Lenka Kotackova, Aleksi Sedo
Fibroblast activation protein (FAP, seprase) is a serine protease with post-proline dipeptidyl peptidase and endopeptidase enzymatic activity. FAP is upregulated in several tumor types, while its expression in healthy adult tissues is scarce. FAP molecule itself and FAP+ stromal cells play an important although probably context-dependent and tumor type-specific pathogenetic role in tumor progression. We provide an overview of FAP expression under both physiological and pathological conditions with focus on human malignancies...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772491/calpain-inhibition-reduces-nmda-receptor-rundown-in-rat-substantia-nigra-dopamine-neurons
#14
Jerry Zhao, Michel Baudry, Susan Jones
Repeated activation of N-Methyl-d-aspartate receptors (NMDARs) causes a Ca2+ -dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca2+ -dependent regulatory protein has not been identified. The role of the Ca2+ -dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 ('P7'), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 μM) or MDL-28170 (30 μM) significantly reduced whole-cell NMDAR current rundown...
May 4, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29772327/creation-of-abdominal-aortic-aneurysms-in-sheep-by-extrapolation-of-rodent-models-is-it-feasible
#15
Peter Verbrugghe, Jelle Verhoeven, Marnick Clijsters, Dominique Vervoort, Walter Coudyzer, Eric Verbeken, Bart Meuris, Paul Herijgers
BACKGROUND: Aortic abdominal aneurysms are a potentially deathly disease, needing surgical or endovascular treatment. To evaluate potentially new diagnostic tools and treatments a large animal model, which not only resembles the morphological characteristics but also the pathophysiological background, would be useful. MATERIALS AND METHODS: Rodent animal aneurysm models were extrapolated to sheep. Four groups were created: intraluminal infusion with an elastase-collagenase solution (n=4), infusion with elastase-collagenase solution combined with proximal stenosis (n=7), aortic xenograft (n=3), and elastase-collagenase treated xenograft (n=4)...
May 14, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29771460/targeting-prostate-cancer-prostate-specific-membrane-antigen-based-diagnosis-and-therapy
#16
REVIEW
Till Wüstemann, Uwe Haberkorn, John Babich, Walter Mier
The high incidence rates of prostate cancer (PCa) raise demand for improved therapeutic strategies. Prostate tumors specifically express the prostate-specific membrane antigen (PSMA), a membrane-bound protease. As PSMA is highly overexpressed on malignant prostate tumor cells and as its expression rate correlates with the aggressiveness of the disease, this tumor-associated biomarker provides the possibility to develop new strategies for diagnostics and therapy of PCa. Major advances have been made in PSMA targeting, ranging from immunotherapeutic approaches to therapeutic small molecules...
May 17, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29771277/effect-of-antiretroviral-therapy-on-plasma-concentrations-of-chloroquine-and-desethyl-chloroquine
#17
Matthew M Ippolito, Jeffrey M Jacobson, Michael M Lederman, Markus Winterberg, Joel Tarning, Theresa A Shapiro, Charles Flexner
The effect of antiretroviral therapy (ART) on chloroquine and desethyl-chloroquine plasma concentrations was evaluated in clinical trial participants. Concentrations did not differ among participants on protease inhibitor-based ART (n=9), efavirenz-based ART (n=15), other ART (n=8), and those not on ART (n=31). Efavirenz appeared to inhibit chloroquine desethylation.
May 16, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29771001/total-chemical-synthesis-of-sumo-and-sumo-abps-to-profile-activity-of-sumo-specific-proteases
#18
Monique Priscilla Catharina Mulder, Remco Merkx, Katharina Witting, Dharjath Hameed, Dris El Atmioui, Lindsey Lelieveld, Frauke Liebelt, Jacques Neefjes, Ilana Berlin, Alfred Vertegaal, Huib Ovaa
SUMO, a post-translational modifier critical for cell cycle progression and genome stability, plays a role in tumorigenesis rendering SUMO-specific enzymes as potential pharmacological targets. However, systematic generation of tools for activity profiling of SUMO-specific enzymes has proven challenging, leading us to develop a diversifiable synthetic platform for a SUMO toolbox using a direct linear synthesis protocol, permitting N- and C-terminal labeling strategies to incorporate dyes and reactive warheads, respectively...
May 17, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29770748/the-effect-of-switching-protease-inhibitors-to-raltegravir-on-endothelial-function-in-hiv-infected-patients
#19
Maaike Krikke, Kiki Tesselaar, Guido E L van den Berk, Sigrid A Otto, Laura H Freriks, Steven F L van Lelyveld, Frank J L Visseren, Andy I M Hoepelman, Joop E Arends
Objective Lipid management is one of the cornerstones of cardiovascular risk reduction. Treatment of HIV infection with protease inhibitors (PIs) may cause dyslipidaemia, whilst the integrase inhibitor raltegravir (RAL) has a relatively favorable effect on plasma lipids. We examined the effect of switching from PIs to RAL on endothelial function, and its effect on immunological and inflammatory parameters. Methods We performed a 16-week open-label prospective crossover study: 8 weeks intervention (switch PIs to RAL) and 8 weeks control (unchanged cART regimen)...
April 2018: HIV Clinical Trials
https://www.readbyqxmd.com/read/29769566/antiretroviral-drugs-alter-the-content-of-extracellular-vesicles-from-hiv-1-infected-cells
#20
Catherine DeMarino, Michelle L Pleet, Maria Cowen, Robert A Barclay, Yao Akpamagbo, James Erickson, Nicaise Ndembe, Manhattan Charurat, Jibreel Jumare, Sunday Bwala, Peter Alabi, Max Hogan, Archana Gupta, Nicole Noren Hooten, Michele K Evans, Benjamin Lepene, Weidong Zhou, Massimo Caputi, Fabio Romerio, Walter Royal, Nazira El-Hage, Lance A Liotta, Fatah Kashanchi
To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids...
May 16, 2018: Scientific Reports
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