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https://www.readbyqxmd.com/read/29782949/early-detection-of-pancreatic-cancers-in-liquid-biopsies-by-ultrasensitive-fluorescence-nanobiosensors
#1
Madumali Kalubowilage, Obdulia Covarrubias-Zambrano, Aruni P Malalasekera, Sebastian O Wendel, Hongwang Wang, Asanka S Yapa, Lauren Chlebanowski, Yubisela Toledo, Raquel Ortega, Katharine E Janik, Tej B Shrestha, Christopher T Culbertson, Anup Kasi, Stephen Williamson, Deryl L Troyer, Stefan H Bossmann
Numerous proteases, such as matrix metalloproteinases (MMP's), cathepsins (CTS), and urokinase plasminogen activator (UpA), are dysfunctional (that is, over- or under-expressed) in solid tumors, when compared to healthy human subjects. This offers the opportunity to detect early tumors by liquid biopsies. This approach is of particular advantage for the early detection of pancreatic cancer, which is a "silent killer". We have developed fluorescence nanobiosensors for ultrasensitive (sub-femtomolar) arginase and protease detection, consisting of water-dispersible Fe/Fe3 O4 core/shell nanoparticles and two tethered fluorescent dyes: TCPP (Tetrakis(4-carboxyphenyl)porphyrin) and cyanine 5...
May 18, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29781506/articular-cartilage-protection-in-ctsk-mice-is-associated-with-cellular-and-molecular-changes-in-subchondral-bone-and-cartilage-matrix
#2
Fabiana N Soki, Ryu Yoshida, David N Paglia, Le T Duong, Marc F Hansen, Hicham Drissi
Osteoarthritis (OA) is a degenerative disease and a major cause of chronic disability in aging individuals. Cathepsin K (CatK), encoded by the Ctsk gene, has been implicated in the pathogenesis of pycnodysostosis and osteoporosis. The use of a selective inhibitor of CatK was recently shown to delay OA progression in rabbits. However, the cellular mechanisms underlying these protective effects remain unexplored. We examined articular cartilage maintenance and joint bone remodeling using Ctsk null mice (Ctsk-/- ) which underwent destabilization of the medial meniscus (DMM)...
May 21, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29779708/imaging-mass-spectrometry-reveals-direct-albumin-fragmentation-within-the-diabetic-kidney
#3
Kerri J Grove, Nichole M Lareau, Paul A Voziyan, Fenghua Zeng, Raymond C Harris, Billy G Hudson, Richard M Caprioli
Albumin degradation in the renal tubules is impaired in diabetic nephropathy such that levels of the resulting albumin fragments increase with the degree of renal injury. However, the mechanism of albumin degradation is unknown. In particular, fragmentation of the endogenous native albumin has not been demonstrated in the kidney and the enzymes that may contribute to fragmentation have not been identified. To explore this we utilized matrix-assisted laser desorption/ionization imaging mass spectrometry for molecular profiling of specific renal regions without disturbing distinct tissue morphology...
May 17, 2018: Kidney International
https://www.readbyqxmd.com/read/29779627/in-vitro-assessment-of-ribose-modified-two-step-etch-and-rinse-dentine-adhesive
#4
U Daood, J K H Tsoi, P Neelakantan, J P Matinlinna, H A K Omar, M Al-Nabulsi, A S Fawzy
OBJECTIVE: Collagen fibrils aid in anchoring resin composite restorations to the dentine substrate. The aim of the study was to investigate effect of non-enzymatic glycation on bond strength and durability of demineralized dentine specimens in a modified two-step etch-and-rinse dentine adhesive. METHODS: Dentine surfaces were etched with 37% phosphoric acid, bonded with respective in vitro ethanol and acetone adhesives modified with (m/m, 0, 1%, 2% and 3% ribose), restored with restorative composite-resin, and sectioned into resin-dentine slabs and beams to be stored for 24h or 12 months in artificial saliva...
May 17, 2018: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/29777136/functional-proteomic-profiling-of-secreted-serine-proteases-in-health-and-inflammatory-bowel-disease
#5
Alexandre Denadai-Souza, Chrystelle Bonnart, Núria Solà Tapias, Marlène Marcellin, Brendan Gilmore, Laurent Alric, Delphine Bonnet, Odile Burlet-Schiltz, Morley D Hollenberg, Nathalie Vergnolle, Céline Deraison
While proteases are essential in gastrointestinal physiology, accumulating evidence indicates that dysregulated proteolysis plays a pivotal role in the pathophysiology of inflammatory bowel disease (IBD). Nonetheless, the identity of overactive proteases released by human colonic mucosa remains largely unknown. Studies of protease abundance have primarily investigated expression profiles, not taking into account their enzymatic activity. Herein we have used serine protease-targeted activity-based probes (ABPs) coupled with mass spectral analysis to identify active forms of proteases secreted by the colonic mucosa of healthy controls and IBD patients...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29775672/upregulation-of-psmb8-and-cathepsins-in-the-human-brains-of-dementia-with-lewy-bodies
#6
Qunxing Ding, Haiyan Zhu
Proteasome and lysosome are responsible for the homeostasis of proteins, lipids and carbohydrates in cells. Numerous reports indicate the proteolytic pathways have altered functions during neurodegeneration and aging. Dementia with Lewy bodies (DLB) is one of the leading forms of dementia, and the proteolytic alteration in DLB has not yet been fully investigated. This study shows that the components of proteasome and lysosome had selectively altered gene expression and enzymatic functions. Specifically, PSMB8, an inducible proteasomal β subunit, had elevated mRNA level and protein level in DLB brain compared with age-matched controls...
May 16, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29775284/multifunctional-tumor-targeting-cathepsin-b-sensitive-gemcitabine-prodrug-covalently-targets-albumin-in-situ-and-improves-cancer-therapy
#7
Huicong Zhang, Zhisu Sun, Kuanglei Wang, Na Li, Hongxiang Chen, Xiao Tan, Lingxiao Li, Zhonggui He, Jin Sun
We report a new type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs, capable of in situ covalently targeting circulating albumin and then making a hitchhike to the tumor. Specially, less plasma-enzyme deactivation, long plasma half-life, independence on nucleoside transporters, outstanding tumor targeting and site-specific drug release are achieved and such these multifunctional advantages contribute to the dramatically increased in vivo antitumor efficacy.
May 18, 2018: Bioconjugate Chemistry
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
#8
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/29773595/therapeutic-effects-of-the-novel-subtype-selective-histone-deacetylase-hdac-inhibitor-chidamide-on-myeloma-associated-bone-disease
#9
Jingsong He, Qingxiao Chen, Huiyao Gu, Jing Chen, Enfan Zhang, Xing Guo, Xi Huang, Haimeng Yan, DongHua He, Yang Yang, Yi Zhao, Gang Wang, Huang He, Qing Yi, Zhen Cai
Histone deacetylases are promising therapeutic targets in hematological malignancies. In the present work, we investigated the effect of chidamide, a new subtype-selective histone deacetylase inhibitor that was independently produced in China, on multiple myeloma and its associated bone diseases using different models. The cytotoxicity of chidamide toward myeloma is due to its induction of cell apoptosis and cell cycle arrest by increasing the levels of caspase family proteins, including p21 and p27, among others...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773143/sex-and-vaccination-insights-from-female-rats-vaccinated-with-juvenile-specific-proteases-from-fasciola-hepatica
#10
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/29771602/irisin-promotes-proliferation-but-inhibits-differentiation-in-osteoclast-precursor-cells
#11
Yaxian Ma, Xiaoyong Qiao, Rujun Zeng, Ran Cheng, Jun Zhang, Yunyao Luo, Ying Nie, Ying Hu, Zhilan Yang, Jing Zhang, Lin Liu, Wenming Xu, Charles C Xu, Liangzhi Xu
The receptor activator of NF-κB ligand-induced osteoclast differentiation has a critical role in the process of bone metabolism. Overactivation of osteoclastogenesis may result in a series of diseases. Irisin, a novel myokine, which was first reported in 2012, has been proposed to mediate the beneficial metabolic effects of exercise. Studies have demonstrated that irisin targets osteoblasts by promoting osteoblast proliferation and differentiation; however, the underlying mechanism regarding the effect of irisin on osteoclasts remains elusive...
May 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29768975/arresting-dentine-caries-with-silver-diamine-fluoride-what-s-behind-it
#12
M L Mei, E C M Lo, C H Chu
Unlike other fluoride-based caries preventive agents, silver diamine fluoride (SDF) can simultaneously prevent and arrest coronal and root dentine caries. The profound clinical success of SDF has drawn many clinicians and researchers to study the mechanism of SDF in arresting dentine caries. This critical review discusses how silver and fluoride contribute to caries arrest, in terms of their effects on bacteria as well as on the mineral and organic content of dentine. Silver interacts with bacterial cell membrane and bacterial enzymes, which can inhibit bacterial growth...
May 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29765497/di-2-pyridylhydrazone-dithiocarbamate-butyric-acid-ester-exerted-its-proliferative-inhibition-against-gastric-cell-via-ros-mediated-apoptosis-and-autophagy
#13
Xingshuang Guo, Yun Fu, Zhuo Wang, Tingting Wang, Cuiping Li, Tengfei Huang, Fulian Gao, Changzheng Li
Diversified biological activities of dithiocarbamates have attracted widespread attention; improving their feature or exploring their potent action of mechanism is a hot topic in medicinal research. Herein, we presented a study on synthesis and investigation of a novel dithiocarbamate, DpdtbA (di-2-pyridylhydrazone dithiocarbamate butyric acid ester), on antitumor activity. The growth inhibition assay revealed that DpdtbA had important antitumor activity for gastric cancer (GC) cell lines (IC50  = 4.2 ± 0...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29765494/the-oxidant-antioxidant-equilibrium-and-inflammatory-process-indicators-after-an-exercise-test-on-the-alterg-antigravity-treadmill-in-young-amateur-female-athletes
#14
Łukasz Sielski, Paweł Sutkowy, Agnieszka Skopowska, Katarzyna Pawlak-Osińska, Zofia Augustyńska, Katarzyna Hewelt, Radosław Drapała, Alina Woźniak
The AlterG antigravity treadmill allows running with a considerable weight reduction. Physical exercise practiced on this treadmill is an innovative method supporting the treatment of injuries in sports and rehabilitation of patients. The aim of the study was to investigate the effect of a 30 min run on the AlterG treadmill with 80% body weight reduction comparing the effect to the similar effort on the classic treadmill on the redox equilibrium and the activity of selected lysosomal enzymes and a serine protease inhibitor in the blood of amateur minor female volleyball players...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29760175/modulation-of-receptor-protein-tyrosine-phosphatase-sigma-increases-chondroitin-sulfate-proteoglycan-degradation-through-cathepsin-b-secretion-to-enhance-axon-outgrowth
#15
Amanda Phuong Tran, Sapna Sundar, Meigen Yu, Bradley T Lang, Jerry Silver
Severed axon tips reform growth cones following spinal cord injury that fail to regenerate, in part, because they become embedded within an inhibitory extracellular matrix. Chondroitin sulfate proteoglycans (CSPGs) are the major axon inhibitory matrix component that is increased within the lesion scar and in perineuronal nets around deafferented neurons. We have recently developed a novel peptide modulator (Intracellular Sigma Peptide or ISP) of the cognate receptor of CSPGs, protein tyrosine phosphatase sigma (RPTPσ), which has been shown to markedly improve sensorimotor function, micturition, and coordinated locomotor behavior in spinal cord contused rats...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29759138/impact-of-imipramine-on-proteome-of-rat-primary-glial-cells
#16
Sylwia Kedracka-Krok, Bianka Swiderska, Anna M Bielecka-Wajdman, Gabriela Prus, Bozena Skupien-Rabian, Urszula Jankowska, Ewa Obuchowicz
Microglia and astrocytes, two types of glial cells are known to be important targets for antidepressant drugs. Here we used a comprehensive proteomic analysis to examine the effect of imipramine on rat primary mixed glial culture. The two-dimensional differential gel electrophoresis method allowed us to identify 62 proteins that were altered by imipramine. Functional analysis revealed that imipramine influenced the level of proteins involved in oxidative stress; in particular, it elevated the level of glutathione transferases...
July 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29758010/combined-transcriptomics-proteomics-and-bioinformatics-identify-drug-targets-in-spinal-cord-injury
#17
Jure Tica, Elizabeth J Bradbury, Athanasios Didangelos
Spinal cord injury (SCI) causes irreversible tissue damage and severe loss of neurological function. Currently, there are no approved treatments and very few therapeutic targets are under investigation. Here, we combined 4 high-throughput transcriptomics and proteomics datasets, 7 days and 8 weeks following clinically-relevant rat SCI to identify proteins with persistent differential expression post-injury. Out of thousands of differentially regulated entities our combined analysis identified 40 significantly upregulated versus 48 significantly downregulated molecules, which were persistently altered at the mRNA and protein level, 7 days and 8 weeks post-SCI...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29751895/inhibitory-effects-of-chitosan-based-coatings-on-endogenous-enzyme-activities-proteolytic-degradation-and-texture-softening-of-grass-carp-ctenopharyngodon-idellus-fillets-stored-at-4-%C3%A2-c
#18
Dawei Yu, Joe M Regenstein, Jinhong Zang, Wenshui Xia, Yanshun Xu, Qixing Jiang, Fang Yang
The study evaluated the inhibitory effects of chitosan-based coatings on endogenous enzyme activities, proteolytic degradation and texture softening of grass carp (Ctenopharyngodon idellus) fillets stored at 4 °C for 15 days. In general, the inhibitory effects of chitosan coating were worse than that of chitosan composite coatings, which significantly inhibited cathepsin B, B + L and calpain activities of fillets, with the most reductions of 58%, 65% and 41%, respectively when compared to the corresponding values of control fillets...
October 1, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29749721/characterization-of-novel-piperidine-based-inhibitor-of-cathepsin-b-dependent-bacterial-toxins-and-viruses
#19
Stella Hartmann, Renae Lopez Cruz, Saleem Alameh, Chi-Lee C Ho, Amy Rabideau, Bradley L Pentelute, Kenneth A Bradley, Mikhail Martchenko
Exploiting the host endocytic trafficking pathway is a common mechanism by which bacterial exotoxins gain entry to exert virulent effects upon the host cells. A previous study identified a small-molecule, 1-(2,6-dimethyl-1-piperidinyl)-3-[(2-isopropyl-5-methylcyclohexyl)oxy]-2-propanol, that blocks the process of anthrax lethal toxin (LT) cytotoxicity. Here, we report the characterization of the bioactivity of this compound, which we named RC1. We found that RC1 protected host cells independently of LT concentration and also blocked intoxication by other bacterial exotoxins, suggesting that the target of the compound is a host factor...
May 18, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29749483/integrated-bioinformatics-analysis-reveals-that-the-expression-of-cathepsin-s-is-associated-with-lymph-node-metastasis-and-poor-prognosis-in-papillary-thyroid-cancer
#20
Juan Tan, Xiaoxiao Qian, Bin Song, Xiumin An, Tingting Cai, Zhihua Zuo, Dafa Ding, Yibing Lu, Hong Li
The prognosis of the majority of patients with papillary thyroid cancer (PTC) is excellent, although there are patients who experience disease recurrence and progression. The aim of the present study was to identify potential prognostic risk markers in PTC. Differentially expressed genes (DEGs), identified from four Genome Expression Omnibus cohorts were subjected to functional enrichment analyses with Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genome pathways. Hub genes, filtered from cytoHubba, were validated using the The Cancer Genome Atlas (TCGA) cohort, and their associations with clinicopathological features and prognosis were analyzed...
May 8, 2018: Oncology Reports
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