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https://www.readbyqxmd.com/read/28915633/selection-of-optimal-molecular-targets-for-tumor-specific-imaging-in-pancreatic-ductal-adenocarcinoma
#1
Willemieke S Tummers, Arantza Farina-Sarasqueta, Martin C Boonstra, Hendrica A Prevoo, Cornelis F Sier, Jan S Mieog, Johannes Morreau, Casper H van Eijck, Peter J Kuppen, Cornelis J van de Velde, Bert A Bonsing, Alexander L Vahrmeijer, Rutger-Jan Swijnenburg
Discrimination of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) or peritumoral inflammation is challenging, both at preoperative imaging and during surgery, but it is crucial for proper therapy selection. Tumor-specific molecular imaging aims to enhance this discrimination and to help select and stratify patients for resection. We evaluated various biomarkers for the specific identification of PDAC and associated lymph node metastases. Using immunohistochemistry (IHC), expression levels and patterns were investigated of integrin αvβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), Cathepsin E (Cath E), epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-MET), thymocyte differentiation antigen 1 (Thy1), and urokinase-type plasminogen activator receptor (uPAR)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915464/sar-studies-of-some-acetophenone-phenylhydrazone-based-pyrazole-derivatives-as-anticathepsin-agents
#2
Neera Raghav, Mamta Singh
Cathepsins have emerged as promising molecular targets in a number of diseases such as Alzeimer's, inflammation and cancer. Elevated cathepsin's levels and decreased cellular inhibitor concentrations have emphasized the search for novel inhibitors of cathepsins. The present work is focused on the design and synthesis of some acetophenone phenylhydrazone based pyrazole derivatives as novel non peptidyl inhibitors of cathepsins B, H and L. The synthesized compounds after characterization have been explored for their inhibitory potency against cathepsins B, H and L...
August 31, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28914985/cherubism-mice-also-deficient-in-c-fos-exhibit-inflammatory-bone-destruction-executed-by-macrophages-that-express-mmp14-despite-the-absence-of-trap-osteoclasts
#3
Mizuho Kittaka, Kotoe Mayahara, Tomoyuki Mukai, Tetsuya Yoshimoto, Teruhito Yoshitaka, Jeffrey P Gorski, Yasuyoshi Ueki
Currently, it is believed that osteoclasts positive for tartrate-resistant acid phosphatase (TRAP +) are the exclusive bone-resorbing cells responsible for focal bone destruction in inflammatory arthritis. Recently, a mouse model of cherubism (Sh3bp2(KI/KI) ) with a homozygous gain-of-function mutation in the SH3-domain binding protein 2 (SH3BP2) was shown to develop auto-inflammatory joint destruction. Here, we demonstrate that Sh3bp2(KI/KI) mice also deficient in the FBJ osteosarcoma oncogene (c-Fos) still exhibit noticeable bone erosion at the distal tibia even in the absence of osteoclasts at 12 weeks old...
September 15, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28913790/delivery-of-hsp90-inhibitor-using-water-soluble-polymeric-conjugates-with-high-drug-payload
#4
Jose A Suárez Del Pino, Rohit Kolhatkar
PURPOSE: HSP90 (Heat shock protein 90kD) has been validated as a therapeutic target in Castrate Resistant Prostate Cancer. Unfortunately, HSP90 inhibitors suffer from dose-limiting toxicities that hinder their clinical applications. Previously developed polymeric delivery systems for HSP90 inhibitors had either low drug content or low biological activity suggesting the need for better delivery system for HSP90 inhibitors. METHODS: We developed a simplified synthetic strategy to prepare polyethylene glycol based water-soluble polymeric system for model HSP90 inhibitor geldanamycin (GDM)...
September 14, 2017: Pharmaceutical Research
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
#5
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/28911904/functional-characterization-of-candidate-antigens-of-hyalomma-anatolicum-and-evaluation-of-its-cross-protective-efficacy-against-rhipicephalus-microplus
#6
Binod Kumar, H V Manjunathachar, Gaurav Nagar, G Ravikumar, José de la Fuente, B C Saravanan, Srikant Ghosh
Hyalomma anatolicum and Rhipicephalus microplus seriously affect dairy animals and immunization of host is considered as a sustainable option for the management of the tick species. Identification and validation of protective molecules are the major challenges in developing a cross-protective vaccine. The subolesin (SUB), calreticulin (CRT) and cathepsin L-like cysteine proteinase (CathL) genes of H. anatolicum were cloned, sequenced and analysed for sequence homology. Both Ha-SUB and Ha-CRT genes showed very high level of homogeneity within the species (97...
September 11, 2017: Vaccine
https://www.readbyqxmd.com/read/28911315/direct-quantification-of-protein-glycan-phosphorylation
#7
Stephanie A Ketcham, Muhammad Ashraf, Chikkathur N Madhavarao
Phosphorylation is an important post-translational modification (PTM) of proteins and a critical quality attribute for protein therapeutics, especially if it is required for protein function or sub-cellular targeting. Most current methods to quantify phosphorylation are time-consuming, indirect, or require specific instrumentation and technical skills. Here, we report the adaptation of a phosphate-specific binding dye and common laboratory instruments for quantification of relative amounts of phosphorylated glycans as well as phosphorylation of amino acid residues on the backbones of proteins...
September 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/28910323/comparative-proteomic-analyses-reveal-the-proteome-response-to-short-term-drought-in-italian-ryegrass-lolium-multiflorum
#8
Ling Pan, Zhongfu Yang, Jianping Wang, Pengxi Wang, Xiao Ma, Meiliang Zhou, Ji Li, Nie Gang, Guangyan Feng, Junming Zhao, Xinquan Zhang
Drought is a major abiotic stress that impairs growth and productivity of Italian ryegrass. Comparative analysis of drought responsive proteins will provide insight into molecular mechanism in Lolium multiflorum drought tolerance. Using the iTRAQ-based approach, proteomic changes in tolerant and susceptible lines were examined in response to drought condition. A total of 950 differentially accumulated proteins was found to be involved in carbohydrate metabolism, amino acid metabolism, biosynthesis of secondary metabolites, and signal transduction pathway, such as β-D-xylosidase, β-D-glucan glucohydrolase, glycerate dehydrogenase, Cobalamin-independent methionine synthase, glutamine synthetase 1a, Farnesyl pyrophosphate synthase, diacylglycerol, and inositol 1, 4, 5-trisphosphate, which might contributed to enhance drought tolerance or adaption in Lolium multiflorum...
2017: PloS One
https://www.readbyqxmd.com/read/28906320/changes-in-proteases-antiproteases-and-bioactive-proteins-from-mother-s-breast-milk-to-the-premature-infant-stomach
#9
Veronique Demers-Mathieu, Søren Drud Nielsen, Mark A Underwood, Robyn Borghese, David C Dallas
OBJECTIVES: Our previous studies suggested that human milk proteases begin to hydrolyze proteins in the mammary gland and continue within the term infant stomach. No research has measured milk protease and pepsin activity in the gastric aspirates of preterm infants after human milk feeding. This study investigated how the concentrations of human milk proteases and protease inhibitors changed in the premature infant stomach. METHODS: Human milk and infant gastric samples were collected from 18 preterm-delivering mother-infant pairs (24-32 wk gestational age)...
September 12, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28904354/identification-and-characterization-of-the-novel-reversible-and-selective-cathepsin-x-inhibitors
#10
Urša Pečar Fonović, Ana Mitrović, Damijan Knez, Tanja Jakoš, Anja Pišlar, Boris Brus, Bojan Doljak, Jure Stojan, Simon Žakelj, Jurij Trontelj, Stanislav Gobec, Janko Kos
Cathepsin X is a cysteine peptidase involved in the progression of cancer and neurodegenerative diseases. Targeting this enzyme with selective inhibitors opens a new possibility for intervention in several therapeutic areas. In this study triazole-based reversible and selective inhibitors of cathepsin X have been identified. Their selectivity and binding is enhanced when the 2,3-dihydrobenzo[b][1,4]dioxine moiety is present as the R(1) substituent. Of a series of selected triazole-benzodioxine derivatives, compound 22 is the most potent inhibitor of cathepsin X carboxypeptidase activity (Ki = 2...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904096/ripk1-mediates-a-disease-associated-microglial-response-in-alzheimer-s-disease
#11
Dimitry Ofengeim, Sonia Mazzitelli, Yasushi Ito, Judy Park DeWitt, Lauren Mifflin, Chengyu Zou, Sudeshna Das, Xian Adiconis, Hongbo Chen, Hong Zhu, Michelle A Kelliher, Joshua Z Levin, Junying Yuan
Dysfunction of microglia is known to play an important role in Alzheimer's disease (AD). Here, we investigated the role of RIPK1 in microglia mediating the pathogenesis of AD. RIPK1 is highly expressed by microglial cells in human AD brains. Using the amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mouse model, we found that inhibition of RIPK1, using both pharmacological and genetic means, reduced amyloid burden, the levels of inflammatory cytokines, and memory deficits. Furthermore, inhibition of RIPK1 promoted microglial degradation of Aβ in vitro...
September 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28904019/cathepsin-b-mediated-cd18-shedding-regulates-leukocyte-recruitment-from-angiogenic-vessels
#12
Shintaro Nakao, Souska Zandi, Dawei Sun, Ali Hafezi-Moghadam
Cathepsin B (CtsB) contributes to atherosclerosis and cancer progression by processing the extracellular matrix and promoting angiogenesis. Although CtsB was reported to promote and reduce angiogenesis, there is no mechanistic explanation that reconciles this apparent discrepancy. CtsB cleaves CD18 from the surface of immune cells, but its contribution to angiogenesis has not been studied. We developed an in vivo technique for visualization of immune cell transmigration from corneal vessels toward implanted cytokines...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28902875/interferon-%C3%AE-treatment-in-vitro-elicits-some-of-the-changes-in-cathepsin-s-and-antigen-presentation-characteristic-of-lacrimal-glands-and-corneas-from-the-nod-mouse-model-of-sj%C3%A3-gren-s-syndrome
#13
Zhen Meng, Wannita Klinngam, Maria C Edman, Sarah F Hamm-Alvarez
Inflammation and impaired secretion by lacrimal and salivary glands are hallmarks of the autoimmune disease, Sjögren's Syndrome. These changes in the lacrimal gland promote dryness and inflammation of the ocular surface, causing pain, irritation and corneal damage. The changes that initiate and sustain autoimmune inflammation in the lacrimal gland are not well-established. Here we demonstrate that interferon-γ (IFN-γ) is significantly elevated in lacrimal gland and tears of the male NOD mouse, a model of autoimmune dacryoadenitis which exhibits many ocular characteristics of Sjögren's Syndrome, by 12 weeks of age early in lacrimal gland inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28902811/-oxidative-carbonylation-of-proteins-in-experimental-hind-limb-ischaemia-reperfusion-injury
#14
R E Kalinin, A S Pshennikov, I A Suchkov, Iu V Abalenikhina, N D Mzhavanadze
Formation of carbonylated protein derivatives is one of the key signalling pathways in cellular damage and may be regarded as a reliable marker in cellular injury. It allows evaluating both direct effects of reactive oxygen species and indirect interrelations with the secondary by-products of oxidation. The present study was undertaken to investigate the activity of lysosomal cysteine proteinases (cathepsins B and L) in blood serum and the arterial wall in an experimental model of ischaemia and ischaemia-reperfusion injury...
2017: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/28899738/angiomyomatous-hamartoma-of-lymph-nodes-revisited-clinico-pathologic-study-of-21-cases-emphasizing-its-distinction-from-lymphangioleiomyomatosis-of-lymph-nodes
#15
Michelle Moh, Ankur Sangoi, Joseph T Rabban
Angiomyomatous hamartoma of lymph nodes (AMH-LN) is an uncommon benign proliferation of smooth muscle, blood vessels, collagenous stroma and adipocytes, most commonly affecting inguinal LN. A similar constellation of cell types constitutes various members of the perivascular epithelioid cell tumor (PEComa) family, including lymphangioleiomyomatosis (LAM) which can involve LN in women. Because some LN-LAM patients have tuberous sclerosis complex (TSC) and/or other PEComa family lesions, it is clinically relevant to distinguish LN-LAM from AMH-LN...
September 9, 2017: Human Pathology
https://www.readbyqxmd.com/read/28899511/safflower-bud-inhibits-rankl-induced-osteoclast-differentiation-and-prevents-bone-loss-in-ovariectomized-mice
#16
Joo-Hee Choi, Seul-Ki Lim, Dong-Il Kim, Min-Jung Park, Young-Kuk Kim, An-Chul Lee, Young-Min Kim, Soo-Jin Yang, Jong-Hwan Park
BACKGROUND: The powder and extract of safflower seeds are known to be effective in the prevention of bone loss in ovariectomized animals. However, the inhibitory effect and molecular mechanisms of safflower bud (SB), the germinated safflower, on bone destruction is unclear. PURPOSE: The present study was designed to investigate the inhibitory effect and molecular mechanism of SB on osteoclastic differentiation and on bone loss in ovarietomized (OVX) mice. METHODS: Osteoclastogenesis was determined by TRAP staining, F-actin ring formation, and bone resorption assay...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28898495/clinical-features-of-cystatin-a-expression-in-patients-with-pancreatic-ductal-adenocarcinoma
#17
Takuya Komura, Hisashi Takabatake, Kenichi Harada, Masatoshi Yamato, Masaki Miyazawa, Keiko Yoshida, Masao Honda, Takashi Wada, Hirohisa Kitagawa, Tetsuo Ohta, Shuichi Kaneko, Yoshio Sakai
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy known, with an extremely poor prognosis due to the lack of an efficient diagnostic scheme and no radical treatment option, except surgery. Therefore, understanding the pathophysiology of, and finding a novel biomarker to detect, PDAC should be prioritized. We observed an increase in mRNA expression of the cysteine protease inhibitor cystatin A (CSTA) in CD4+T cells in peripheral blood cells of 9 patients with PDAC, compared with the expression in 7 healthy volunteers...
September 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28892869/structural-analysis-of-the-interaction-between-jaburetox-an-intrinsically-disordered-protein-and-membrane-models
#18
Valquiria Broll, Anne Helene S Martinelli, Fernanda C Lopes, Leonardo L Fruttero, Barbara Zambelli, Edoardo Salladini, Olena Dobrovolska, Stefano Ciurli, Celia R Carlini
Jack bean urease is entomotoxic to insects with cathepsin-like digestive enzymes, and its toxicity is mainly caused by a polypeptide called Jaburetox (Jbtx), released by cathepsin-dependent hydrolysis of the enzyme. Jbtx is intrinsically disordered in aqueous solution, as shown by CD and NMR. Jbtx is able to alter the permeability of membranes, hinting to a role of Jbtx-membrane interaction as the basis for its toxicity. The present study addresses the structural aspects of this interaction by investigating the behaviour of Jbtx when in contact with membrane models, using nuclear magnetic resonance and circular dichroism spectroscopies in the absence or presence of micelles, large unilamellar vesicles, and bicelles...
August 30, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28887920/isolation-of-natural-products-with-anti-ageing-activity-from-the-fruits-of-platanus-orientalis
#19
Sofia Chatzigeorgiou, Quoc Dang Thai, Job Tchoumtchoua, Konstantinos Tallas, Eleni N Tsakiri, Issidora Papassideri, Maria Halabalaki, Alexios-Leandros Skaltsounis, Ioannis P Trougakos
BACKGROUND: Ageing is defined as the time-dependent decline of functional capacity and stress resistance resulting in increased morbidity and mortality. HYPOTHESIS/PURPOSE: Reportedly, these effects can be delayed by mild genetic or pharmacological activation of the main modules of the proteostasis network. STUDY DESIGN-METHODS: By employing advanced phytochemical methods we isolated natural products from the fruits of Platanus orientalis and studied (via a bio-guided approach) their effects in Drosophila flies, as well as in normal human fibroblasts...
September 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28887075/role-of-cathepsin-k-in-the-development-of-chronic-subdural-hematoma
#20
Satoshi Tsutsumi, Ikuko Ogino, Masakazu Miyajima, Senshu Nonaka, Masanori Ito, Yukimasa Yasumoto, Hajime Arai
Despite extensive investigations, the process of development of chronic subdural hematoma (CSDH) is not known. The present study aims to investigate CSDH by measuring biomarkers in it, gas analysis, and immunohistochemical examination. A total of 42 patients with symptomatic CSDH who underwent burr-hole drainage were enrolled. Intraoperatively, hematoma fluid and peripheral venous blood (PVCSDH) were simultaneously collected. As controls, peripheral venous blood (PVControl) and intracranial cerebrospinal fluid (CSF) were collected from other subjects during other surgeries...
September 5, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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