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https://www.readbyqxmd.com/read/28918591/platform-model-describing-pharmacokinetic-properties-of-vc-mmae-antibody-drug-conjugates
#1
Matts Kågedal, Leonid Gibiansky, Jian Xu, Xin Wang, Divya Samineni, Shang-Chiung Chen, Dan Lu, Priya Agarwal, Bei Wang, Ola Saad, Neelima Koppada, Bernard M Fine, Jin Y Jin, Sandhya Girish, Chunze Li
Antibody-drug conjugates (ADCs) developed using the valine-citrulline-MMAE (vc-MMAE) platform, consist of a monoclonal antibody (mAb) covalently bound with a potent anti-mitotic toxin (MMAE) through a protease-labile vc linker. Recently, clinical data for a variety of vc-MMAE ADCs has become available. The goal of this analysis was to develop a platform model that simultaneously described antibody-conjugated MMAE (acMMAE) pharmacokinetic (PK) data from eight vc-MMAE ADCs, against different targets and tumor indications; and to assess differences and similarities of model parameters and model predictions, between different compounds...
September 16, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28917670/morphological-characterization-and-biocontrol-effects-of-vibrio-vulnificus-phages-against-vibriosis-in-the-shrimp-aquaculture-environment
#2
P Srinivasan, P Ramasamy
The re-emerging field of phage therapy is the potential biocontrol agents for the transfer of virulence factor and to kill their bacterial hosts. In this study, the lytic Vibrio vulnificus phages were studied to provide a better understanding of phage-host interactions and development of phage therapy. Four new V. vulnificus phages were detected from shrimp aquaculture system, named VV1, VV2, VV3 and VV4. All lytic V. vulnificus phages are the Tecviruses of the family Tectiviridae with typical double layered elongated icosahedral head and tailless morphology...
September 13, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28917645/anti-fibrinolytic-and-anti-microbial-activities-of-a-serine-protease-inhibitor-from-honeybee-apis-cerana-venom
#3
Jie Yang, Kwang Sik Lee, Bo Yeon Kim, Yong Soo Choi, Hyung Joo Yoon, Jingming Jia, Byung Rae Jin
Bee venom contains a variety of peptide constituents, including low-molecular-weight protease inhibitors. While the putative low-molecular-weight serine protease inhibitor Api m 6 containing a trypsin inhibitor-like cysteine-rich domain was identified from honeybee (Apis mellifera) venom, no anti-fibrinolytic or anti-microbial roles for this inhibitor have been elucidated. In this study, we identified an Asiatic honeybee (A. cerana) venom serine protease inhibitor (AcVSPI) that was shown to act as a microbial serine protease inhibitor and plasmin inhibitor...
September 13, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28917489/the-effects-of-single-or-combined-administration-of-galactooligosaccharide-and-pediococcus-acidilactici-on-cutaneous-mucus-immune-parameters-humoral-immune-responses-and-immune-related-genes-expression-in-common-carp-cyprinus-carpio-fingerlings
#4
Maryam Modanloo, Siavash Soltanian, Mostafa Akhlaghi, Seyed Hossein Hoseinifar
The present study was performed to investigate the effects of single or combined administration of galactooligosaccharide (GOS) and Pediococcus acidilactici on cutaneous mucus immune parameters, humoral immune responses and immune related genes expression in common carp (Cyprinus carpio) fingerlings. Carps were fed experimental diets for 8 weeks as follows: non-supplemented (Control), prebiotic diet (10 g/kg GOS), probiotic diet (1 g/kg [0.9 × 10(7) CFU] lyophilized P. acidilactici) and synbiotic diet (10 GOS in combination with 1 g/kg [0...
September 13, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28917450/a-novel-class-of-plasmodial-clpp-protease-inhibitors-as-potential-antimalarial-agents
#5
Sourabh Mundra, Vandana Thakur, Angelica M Bello, Sumit Rathore, Mohd Asad, Lianhu Wei, Jane Yang, Sai Kumar Chakka, Radhakrishnan Mahesh, Pawan Malhotra, Asif Mohmmed, Lakshmi P Kotra
The prokaryotic ATP-dependent ClpP protease, localized in the relict plastid of malaria parasite, represents a potential drug target. In the present study, we utilized in silico structure-based screening and medicinal chemistry approaches to identify a novel pyrimidine series of compounds inhibiting P. falciparum ClpP protease activity and evaluated their antiparasitic activities. Structure-activity relationship indicated that morpholine moiety at C2, an aromatic substitution at N3 and a 4-oxo moiety on the pyrimidine are important for potent inhibition of ClpP enzyme along with antiparasiticidal activity...
September 5, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28917301/cysteine-protease-30-cp30-contributes-to-adhesion-and-cytopathogenicity-in-feline-tritrichomonas-foetus
#6
Emily N Gould, Richard Giannone, Stephen A Kania, M Katherine Tolbert
Tritrichomonas foetus (T. foetus) is a flagellated protozoan parasite that is recognized as a significant cause of diarrhea in domestic cats with a prevalence rate as high as 30%. No drugs have been shown to consistently eliminate T. foetus infection in all cats. Cysteine proteases (CPs) have been identified as mediators of T. foetus-induced adhesion-dependent cytotoxicity to the intestinal epithelium. These CPs represent novel targets for the treatment of feline trichomonosis. However, cats also produce CPs that are part of life-critical systems...
September 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28917266/urinary-biomarkers-in-prostate-cancer-detection-and-monitoring-progression
#7
REVIEW
Duojia Wu, Jie Ni, Julia Beretov, Paul Cozzi, Mark Willcox, Valerie Wasinger, Bradley Walsh, Peter Graham, Yong Li
Prostate cancer (CaP) is the most common cancer in men and the second leading cause of cancer deaths in males in Australia. Although serum prostate-specific antigen (PSA) has been the most widely used biomarker in CaP detection for decades, PSA screening has limitations such as low specificity and potential association with over-diagnosis. Current biomarkers used in the clinic are not useful for the early detection of CaP, or monitoring its progression, and have limited value in predicting response to treatment...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28916383/heterologous-expression-and-structure-function-relationship-of-low-temperature-and-alkaline-active-protease-from-acinetobacter-sp-ihb-b-5011-mn12
#8
Richa Salwan, Vivek Sharma, Mohinder Pal, Ramesh Chand Kasana, Sudesh Kumar Yadav, Arvind Gulati
The gene encoding protease from Acinetobacter sp. IHB B 5011(MN12) was cloned and expressed in Escherichia coli BL21(DE3). The nucleotide sequence revealed 1323bp ORF encoding 441 amino acids protein with molecular weight 47.2kDa. The phylogenetic analysis showed clustering of Alp protease with subtilisin-like serine proteases of S8 family. The amino acid sequence was comprised of N-terminal signal peptide 1-21 amino acids, pre-peptide 22-143 amino acids, peptidase S8 domain 144-434 amino acids, and pro-peptide 435-441 amino acids at C-terminus...
September 12, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28916188/mast-cell-chymase-decreases-the-severity-of-group-b-streptococcus-infections
#9
Claire Gendrin, Nicholas J Shubin, Erica Boldenow, Sean Merillat, Morgan Clauson, Danny Power, Kelly S Doran, Magnus Abrink, Gunnar Pejler, Lakshmi Rajagopal, Adrian M Piliponsky
BACKGROUND: Group B Streptococcus (GBS) or Streptococcus agalactiae are ß-hemolytic, Gram-positive bacteria that colonize the lower genital tract of women and are frequently associated with infections during pregnancy. Innate immune defenses are critical for controlling GBS dissemination and systemic infection. Mast cells are resident sentinel cells that come into contact with pathogens early during colonization and infection. OBJECTIVE: We aimed to investigate the contribution of chymase to systemic GBS infection and rates of preterm birth...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#10
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915348/activation-of-factor-xiii-is-accompanied-by-a-change-in-oligomerization-state
#11
Boris A Anokhin, Vilius Stribinskis, William L Dean, Muriel C Maurer
Factor XIII A (FXIIIA) is a member of the transglutaminase enzyme family that cross-links both intra- and extracellular protein substrates. To prevent undesired cross-linking, FXIIIA is expressed as an inactive zymogen and exists intracellularly as an A2 homodimer. In plasma, FXIII A2 is complexed with two protective factor XIII B subunits (A2 B2 ) that dissociate upon activation of the zymogen. Based on limited experimental data, activated FXIII was considered a dimer of two catalytically active A subunits...
September 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28915327/adipose-tissue-in-hiv-infection
#12
John R Koethe
HIV infection and antiretroviral therapy (ART) treatment exert diverse effects on adipocytes and stromal-vascular fraction cells, leading to changes in adipose tissue quantity, distribution, and energy storage. A HIV-associated lipodystrophic condition was recognized early in the epidemic, characterized by clinically apparent changes in subcutaneous, visceral, and dorsocervical adipose depots. Underlying these changes is altered adipose tissue morphology and expression of genes central to adipocyte maturation, regulation, metabolism, and cytokine signaling...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28915040/elucidating-the-interdependence-of-drug-resistance-from-combinations-of-mutations
#13
Debra A Ragland, Troy W Whitfield, Sook-Kyung Lee, Ronald Swanstrom, Konstantin B Zeldovich, Nese Kurt Yilmaz, Celia A Schiffer
HIV-1 protease is responsible for the cleavage of 12 non-homologous sites within the Gag and Gag-Pro-Pol polyproteins in the viral genome. Under the selective pressure of protease inhibition, the virus evolves mutations within (primary) and outside of (secondary) the active site allowing the protease to process substrates while simultaneously countering inhibition. The primary protease mutations impede inhibitor binding directly, while the secondary mutations are considered accessory mutations that compensate for a loss in fitness...
September 15, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28914450/changes-in-composition-and-content-of-food-derived-peptide-in-human-blood-after-daily-ingestion-of-collagen-hydrolysate-for-4-weeks
#14
Yasutaka Shigemura, Asahi Suzuki, Mihoko Kurokawa, Yosio Sato, Kenji Sato
BACKGROUND: daily ingestion of collagen hydrolysate improves skin and joint conditions. It has been speculated that the beneficial effects are exerted by food-derived hydroxyproline (Hyp) peptides, which are detected in human blood after single ingestions. In the present study, to investigate the detailed relationship of the beneficial effects of Hyp-peptides, we examined the concentrations of Hyp-peptides in human blood before and after daily ingestion. RESULTS: Hyp-peptides increased to a maximum level at 1 h after ingestion and reverted to their initial levels within 24 h during daily ingestion...
September 15, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28913881/effect-of-negative-dietary-cation-anion-differences-on-carcass-characteristics-and-beef-tenderness-of-japanese-black-steers
#15
Kyohei Ishida, Kazuo Hirano
Lowering dietary cation-anion differences (DCAD) can enhance responsiveness to Ca-homeostatic hormones and increase Ca availability, which might have potential to activate a Ca-dependent protease, calpain, and to enhance postmortem myofibrillar proteolysis. In this study, we investigated the effects of DCAD manipulation on calpain activity and beef tenderness in Japanese Black cattle which are characterized by their high marbling. Thirty-six Japanese Black steers were allotted to one of two treatments: (i) control (CON; DCAD +6...
September 15, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28913669/resolving-distinct-molecular-origins-for-copper-effects-on-pai-1
#16
Joel C Bucci, Carlee S McClintock, Yuzhuo Chu, Gregory L Ware, Kayla D McConnell, Joseph P Emerson, Cynthia B Peterson
Components of the fibrinolytic system are subjected to stringent control to maintain proper hemostasis. Central to this regulation is the serpin plasminogen activator inhibitor-1 (PAI-1), which is responsible for specific and rapid inhibition of fibrinolytic proteases. Active PAI-1 is inherently unstable and readily converts to a latent, inactive form. The binding of vitronectin and other ligands influences stability of active PAI-1. Our laboratory recently observed reciprocal effects on the stability of active PAI-1 in the presence of transition metals, such as copper, depending on the whether vitronectin was also present (Thompson et al...
September 14, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28913553/dual-inhibition-of-cathepsin-g-and-chymase-reduces-myocyte-death-and-improves-cardiac-remodeling-after-myocardial-ischemia-reperfusion-injury
#17
Bahman Hooshdaran, Mikhail A Kolpakov, Xinji Guo, Sonni A Miller, Tao Wang, Douglas G Tilley, Khadija Rafiq, Abdelkarim Sabri
Early reperfusion of ischemic cardiac tissue increases inflammatory cell infiltration which contributes to cardiomyocyte death and loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Neutrophil- and mast cell-derived proteases, cathepsin G (Cat.G) and chymase, are released early after IR, but their function is complicated by potentially redundant actions and targets. This study investigated whether a dual inhibition of Cat.G and chymase influences cardiomyocyte injury and wound healing after experimental IR in mice...
September 14, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28912582/evolution-of-gag-and-gp41-in-patients-receiving-ritonavir-boosted-protease-inhibitors
#18
Justen Manasa, Vici Varghese, Sergei L Kosakovsky Pond, Soo-Yon Rhee, Philip L Tzou, W Jeffrey Fessel, Karen S Jang, Elizabeth White, Thorsteinn Rögnvaldsson, David A Katzenstein, Robert W Shafer
Several groups have proposed that genotypic determinants in gag and the gp41 cytoplasmic domain (gp41-CD) reduce protease inhibitor (PI) susceptibility without PI-resistance mutations in protease. However, no gag and gp41-CD mutations definitively responsible for reduced PI susceptibility have been identified in individuals with virological failure (VF) while receiving a boosted PI (PI/r)-containing regimen. To identify gag and gp41 mutations under selective PI pressure, we sequenced gag and/or gp41 in 61 individuals with VF on a PI/r (n = 40) or NNRTI (n = 20) containing regimen...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912559/inherent-aggressive-character-of-invasive-and-non-invasive-cells-dictates-the-in-vitro-migration-pattern-of-multicellular-spheroid
#19
Sukanya Gayan, Abhishek Teli, Tuli Dey
Cellular migration, a process relevant to metastasis, is mostly studied in the conventional 2D condition. However, cells cultured in the 3D condition assumed to mimic the in vivo conditions better. The current study is designed to compare an invasive and non-invasive adenocarcinoma cell with an invasive fibrosarcoma cell to understand the migration pattern of the multicellular spheroid. It is observed that conventional haplotaxis, chemotactic and pseudo-3D migration assay cannot distinguish between the invasive and non-invasive cells conclusively under 2D condition...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912497/selective-antibody-activation-through-protease-activated-pro-antibodies-that-mask-binding-sites-with-inhibitory-domains
#20
I-Ju Chen, Chih-Hung Chuang, Yuan-Chin Hsieh, Yun-Chi Lu, Wen-Wei Lin, Chien-Chiao Huang, Ta-Chun Cheng, Yi-An Cheng, Kai-Wen Cheng, Yeng-Tseng Wang, Fang-Ming Chen, Tian-Lu Cheng, Shey-Cherng Tzou
Systemic injection of therapeutic antibodies may cause serious adverse effects due to on-target toxicity to the antigens expressed in normal tissues. To improve the targeting selectivity to the region of disease sites, we developed protease-activated pro-antibodies by masking the binding sites of antibodies with inhibitory domains that can be removed by proteases that are highly expressed at the disease sites. The latency-associated peptide (LAP), C2b or CBa of complement factor 2/B were linked, through a substrate peptide of matrix metalloproteinase-2 (MMP-2), to an anti-epidermal growth factor receptor (EGFR) antibody and an anti-tumor necrosis factor-α (TNF-α) antibody...
September 14, 2017: Scientific Reports
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