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https://www.readbyqxmd.com/read/28821069/preparation-and-pharmacological-evaluation-of-norcantharidin-conjugated-carboxymethyl-chitosan-in-mice-bearing-hepatocellular-carcinoma
#1
Zhiwen Jiang, Jinhua Chi, Baoqin Han, Wanshun Liu
In this study, norcantharidin (NCTD), a small-molecule anticancer drug derived from Chinese traditional medicine blister beetle (Mylabris), was conjugated covalently onto carboxymethyl chitosan (CMCS). Then the hepatocellular carcinoma therapeutic properties and liver-protective effects were investigated through orthotopic transplantation tumor model. Results showed that the obtained CMCS-NCTD demonstrated remarkable anti-growth efficacy against hepatocellular 22 in mice. Significant improvement of the liver injury caused by cancer cells was observed in tumor-bearing mice administrated with CMCS-NCTD...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28820947/dysregulated-mitogen-activated-protein-kinase-and-matrix-metalloproteinase-in-ethanol-induced-cavernosal-dysfunction
#2
Jaqueline Jóice Muniz, Leticia Nogueira Leite, Riccardo Lacchini, Jose E Tanus-Santos, Carlos Renato Tirapelli
We evaluated the effects of ethanol consumption on the mitogen-activated protein kinases (MAPK) and metalloproteinases (MMP) pathways in the rat cavernosal smooth muscle (CSM). Male Wistar rats were treated with ethanol (20% vol./vol.) for six weeks. Quantitative real-time polymerase chain reaction experiments showed that ethanol consumption did not alter mRNA levels of p38MAPK, SAPK/JNK, ERK1/2, MMP-2 or MMP-9 in the rat CSM. Western immunoblotting experiments revealed decreased protein expression of p38MAPK and phosphorylation of SAPK/JNK in the CSM from ethanol-treated rats...
August 18, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28819943/the-mmp-9-timp-1-imbalance-and-the-reduced-level-of-tgf-%C3%AE-in-the-cervical-area-of-amniotic-membrane-is-a-possible-risk-factor-of-prom-and-premature-labor-proof-of-concept-study
#3
Małgorzata Litwiniuk, Małgorzata Radowicka, Alicja Krejner, Mirosław Wielgoś, Tomasz Grzela
OBJECTIVES: To assess the level MMP-9, TIMP-1 and TGF-β in placental and cervical region of amniotic membranes derived from at-term, pre-term and PROM deliveries. MATERIAL AND METHODS: 14 amniotic membranes have been assessed; the quantitative analysis of MMP-9, TGF-β and TIMP-1 was assayed using respective Quantikine Immunoassay Kit. RESULTS: The MMP-9 level in PROM samples was similar to the level of MMP-9 in at-term membranes and comparable between the cervical and placental region of these membranes...
2017: Ginekologia Polska
https://www.readbyqxmd.com/read/28819748/lipoxin-a4-attenuates-bronchopulmonary-dysplasia-via-upregulation-of-let-7c-and-downregulation-of-tgf-%C3%AE-1-signaling-pathway
#4
Xiao-Qing Chen, Sheng-Hua Wu, Yan-Yan Luo, Bing-Jie Li, Shu-Jun Li, Hong-Yan Lu, Rui Jin, Zhong-Yi Sun
Transforming growth factor-β (TGF-β) superfamily members are key regulators for lung development and progress of bronchopulmonary dysplasia (BPD). The mechanisms by which lipoxin A4 (LXA4) attenuates development of BPD have not been clarified. Neonatal murine BPD models were inducted by hyperoxia treatment. Neonatal mice were exposed to room air or 85% O2 hyperoxia with or without treatment with 5S,6R-methyl-LXA4 or anti-TGF-β antibodies. Mouse lung epithelial cells (MLE-12 cells) and mouse embryonic fibroblasts (NIH/3T3 cells) were cultured in room air or 85% O2 followed by treatment of LXA4, anti-TGF-β antibodies, and let-7c mimic/anti-microRNA transfections...
August 17, 2017: Inflammation
https://www.readbyqxmd.com/read/28819366/paracrine-potential-of-the-human-adipose-tissue-derived-stem-cells-to-modulate-balance-between-matrix-metalloproteinases-and-their-inhibitors-in-the-osteoarthritic-cartilage-in-vitro
#5
Jaroslav Denkovskij, Edvardas Bagdonas, Ilona Kusleviciute, Zygmunt Mackiewicz, Ausra Unguryte, Narunas Porvaneckas, Sandrine Fleury, Algirdas Venalis, Christian Jorgensen, Eiva Bernotiene
Adipose tissue represents an abundant source of stem cells. Along with anti-inflammatory effects, ASC secrete various factors that may modulate metabolism of extracellular matrix in osteoarthritic (OA) cartilage, suggesting that the presence of ASC could be advantageous for OA cartilage due to the recovery of homeostasis between matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs). To evaluate these effects, cartilage explants (CE) were cocultured with ASC for 3 and 7 days under stimulation with or without IL-1β...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28818228/phenotypic-and-functional-transformation-in-smooth-muscle-cells-derived-from-varicose-veins
#6
Yongbo Xu, Yuanyuan Bei, Yuan Li, Haibo Chu
OBJECTIVE: Varicose veins (VVs) are a common disorder of venous dilation and tortuosity, but the underlying mechanism is unclear. The functional integrity and phenotypic differences of VVs are also unclear. This study tested the hypothesis that phenotypic and functional differences exist between smooth muscle cells (SMCs) derived from VVs and normal veins. METHODS: SMCs were isolated from 28 samples of varicose great saphenous veins (VGSVs) and normal great saphenous (NGSVs) and cultured...
September 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28818148/cross-sectional-survey-of-physicians-on-providing-volunteer-care-for-in-flight-medical-events
#7
Eric Chatfield, William F Bond, Bradley McCay, Claude Thibeault, Paulo M Alves, Marc Squillante, Joshua Timpe, Courtney J Cook, Raymond E Bertino
BACKGROUND: Airline carriers have equipment, procedures, and protocols in place to handle in-flight medical events (IFMEs). Community physicians may be asked for aid during IFMEs. Cross-Sectional Survey of Physicians on Providing Volunteer Care for In-Flight Medical Events surveyed self-assessed awareness and knowledge, perceived barriers, and suggestions for improving responses to IFMEs. METHODS: We composed a survey regarding clinicians' self-assessed understanding of in-flight resources, procedures, flight environmental issues, and Good Samaritan protections...
September 1, 2017: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28817784/hydrogen-peroxide-regulates-angiogenesis-related-factors-in-tumor-cells
#8
Ana Jerónimo, Gonçalo Rodrigues, Filipe Vilas-Boas, Gabriel G Martins, Ana Bagulho, Carla Real
Tumor angiogenesis is required for tumor development and growth and is regulated by several factors including reactive oxygen species (ROS). Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is a ROS with an important role in cell signaling but how H<sub>2</sub>O<sub>2</sub> regulates tumor angiogenesis is still poorly understood. We have xenografted tumor cells with altered levels of H<sub>2</sub>O<sub>2</sub> by catalase overexpression into zebrafish embryos to study redox-induced tumor neovascularization...
August 17, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28811125/pharmacokinetics-and-pharmacodynamics-of-thiopurines-in-an-in-vitro-model-of-human-hepatocytes-insights-from-an-innovative-mass-spectrometry-assay
#9
Marco Pelin, Elena Genova, Laura Fusco, Monzer Marisat, Ute Hofmann, Diego Favretto, Marianna Lucafò, Andrea Taddio, Stefano Martelossi, Alessandro Ventura, Gabriele Stocco, Matthias Schwab, Giuliana Decorti
AIM: To apply an innovative LC-MS/MS method to quantify thiopurine metabolites in human hepatocytes and to associate them to cytotoxicity. METHODS: Immortalized human hepatocytes (IHH cells) were treated for 48 and 96 h, with 1.4 × 10(-4) M azathioprine and 1.1 × 10(-3) M mercaptopurine, concentrations corresponding to the IC50 values calculated after 96 h exposure in previous cytotoxicity analysis. After treatments, cells were collected for LC-MS/MS analysis to quantify 11 thiopurine metabolites with different level of phosphorylation and viable cells were counted by Trypan blue exclusion assay to determine thiopurines in vitro effect on cell growth and survival...
August 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28811075/regulatory-t-cell-deficient-scurfy-mice-exhibit-a-th2-m2-like-inflammatory-response-in-the-skin
#10
Stefanie Haeberle, Verena Raker, Jessica Haub, Yong O Kim, Shih-Yen Weng, Osman K Yilmaz, Alexander Enk, Kerstin Steinbrink, Detlef Schuppan, Eva N Hadaschik
BACKGROUND: Scurfy mice have a functional defect in regulatory T cells (Treg), which leads to lethal multi-organ inflammation. The missing Treg function results in uncontrolled autoimmune cellular and humoral inflammatory responses. We and others have previously shown that during the course of disease scurfy mice develop severe skin inflammation and autoantibodies including anti-nuclear autoantibodies (ANA). OBJECTIVE: Autoimmune skin inflammation and ANA are hallmarks for the diagnosis of autoimmune connective tissue diseases; therefore we analyzed scurfy mice for typical signs of these diseases...
July 13, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28810543/atorvastatin-has-a-protective-effect-in-a-mouse-model-of-bronchial-asthma-through-regulating-tissue-transglutaminase-and-triggering-receptor-expressed-on-myeloid-cells-1-expression
#11
Ming-Wei Liu, Rong Liu, Hai-Ying Wu, Mei Chen, Min-Na Dong, Yun-Qiao Huang, Chun-Hai Zhang, Yin-Zhong Wang, Jing Xia, Yang Shi, Feng-Mei Xie, Hua Luo, Xin-Yuan Zhao, Wei Wei, Mei-Xian Su
Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810065/olodaterol-shows-anti-fibrotic-efficacy-in-in-vitro-and-in-vivo-models-of-pulmonary-fibrosis
#12
Franziska Elena Herrmann, Lutz Wollin, Johannes Wirth, Florian Gantner, Bärbel Lämmle, Eva Wex
BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by excessive fibroblast activation ultimately leading to scarring of the lungs. Although, the activation of β2 -adrenergic receptors (β2 -AR) has been shown to inhibit pro-fibrotic events primarily in cell lines, the role of β2 -AR agonism has not yet been fully characterized. The aim of our study was to explore the anti-fibrotic activity of the long-acting β2 -AR-agonist olodaterol in primary human lung fibroblasts, and in murine models of pulmonary fibrosis...
August 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28807411/timp3-is-regulated-by-pericytes-upon-shear-stress-detection-leading-to-a-modified-endothelial-cell-response
#13
C Schrimpf, T Koppen, J S Duffield, U Böer, S David, W Ziegler, A Haverich, O E Teebken, M Wilhelmi
OBJECTIVES: Atherosclerosis is a hallmark of cardiovascular disease. Shear stress on endothelial cells has been linked to atherogenesis and to fibrous cap thinning and rupture. Pericytes reside in the sub-endothelial space of vessels and have vasoprotective effects. They are subjected to shear stress when endothelial cell integrity is disrupted. The aim was to investigate the susceptibility and response of pericytes to shear stress. METHODS: Endothelial cells and pericytes were seeded in two dimensional monocultures and co-cultures, and in a novel three dimensional co-culture system and were subjected to no, low and high shear stress (0, 10, 30 dyne/cm(2)) for 48 h...
August 11, 2017: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/28807218/teduglutide-effects-on-gene-regulation-of-fibrogenesis-on-an-animal-model-of-intestinal-anastomosis
#14
Beatriz P Costa, Ana C Gonçalves, Ana M Abrantes, Paulo Matafome, Raquel Seiça, Ana B Sarmento-Ribeiro, Maria Filomena Botelho, Francisco Castro-Sousa
BACKGROUND: Teduglutide is an enterotrophic analog of glucagon-like peptide 2 approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the effects of teduglutide administration on the gene regulation of fibrogenesis during the intestinal anastomotic healing on an animal model. METHODS: Wistar rats (n = 62) were assigned into four groups: "Ileal Resection and Anastomosis" or "Laparotomy," each one subdivided into "Postoperative Teduglutide Administration" or "No Treatment," and sacrificed at the third or at the seventh days, with ileal sample harvesting...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28805547/the-association-between-methylation-levels-of-targeted-genes-and-albuminuria-in-patients-with-early-diabetic-kidney-disease
#15
Ozgur Aldemir, Faruk Turgut, Cumali Gokce
OBJECTIVE: The incidence of diabetes and its complications are greatly increasing world-wide. Diabeticnephropathy (DN) is the main cause of end-stage renal disease and is associated with high morbidity and mortality. It is important to predict patients with high risk for DN in the early stage. We selected the genes which have an important role on diabetic kidney disease. We aimed to investigate the association between DNA methylation levels of targeted genes and albuminuria in patients with early DN...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28804632/the-pattern-of-il-24-mda-7-and-its-cognate-receptors-expression-following-activation-of-human-hepatic-stellate-cells
#16
Iman Jamhiri, Seyed Younes Hosseini, Davood Mehrabani, Zahra Khodabandeh, Ramin Yaghobi, Razieh Dowran, Saber Zahri
Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrosis. Interleukin (IL)-24/melanoma differentiation-associated gene-7 (mda-7) has attracted attention in the pathophysiology of some diseases, while its role in activation/suppression of human HSCs is still unclear. It is important to elucidate whether the expression levels of the IL-24/mda-7 protein and its receptors in HSC cells are changed following activation. LX-2 cells, a human hepatic stellate cell line were activated by a combination of leptin and serum starvation...
August 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28803769/urine-biomarkers-of-tubular-renal-cell-damage-for-the-prediction-of-acute-kidney-injury-after-cardiac-surgery-a-pilot-study
#17
Tanja Mayer, Daniel Bolliger, Markus Scholz, Oliver Reuthebuch, Michael Gregor, Patrick Meier, Martin Grapow, Manfred D Seeberger, Jens Fassl
OBJECTIVE: To evaluate the perioperative course of urine levels of the renal damage biomarkers tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) and to evaluate the predictive value of elevated TIMP-2 × IGFBP7 concentrations to predict acute kidney injury (AKI) early after cardiac on-pump surgery. DESIGN: Prospective, observational cohort study. SETTING: University hospital. PARTICIPANTS: The study comprised 110 consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) between January and March 2014...
April 16, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28799580/risk-prediction-of-acute-kidney-injury-by-timp-2-%C3%A2-igfbp7
#18
M Kimmel, M Schanz, M D Alscher
Acute kidney injury (AKI) is a common syndrome with increased mortality, a heavy burden of illness and high cost. The Kidney Disease Improving Global Outcomes (KDIGO) criteria for staging of AKI have been validated in large patient cohorts and classify AKI into three stages. In order to achieve prevention or early therapy, the focus of scientific interest is early detection and risk prediction of AKI. The combination of the two cell cycle arrest markers [TIMP-2]·[IGFBP7] in the urine shows good results in the risk prediction of AKI in different clinical settings (intensive care medicine, sepsis, cardiac surgery, emergency department)...
June 2017: Drugs of Today
https://www.readbyqxmd.com/read/28799208/ccr2-monocytic-myeloid-derived-immunosuppressive-cells-m-mdsc-inhibit-collagen-degradation-and-promote-lung-fibrosis-by-producing-tgf-%C3%AE-1
#19
Astrid Lebrun, Sandra Lo Re, Mathilde Chantry, Xavier Izquierdo Carerra, Francine Uwambayinema, Doriana Ricci, Raynal Devosse, Saloua Ibouraadaten, Lisa Brombin, Mihaly Palmai-Pallag, Yousof Yakoub, Manolis Pasparakis, Dominique Lison, François Huaux
Monocytes infiltrating scar tissue are predominantly viewed as progenitor cells. Here, we show that tissue CCR2(+) monocytes possess specific immunosuppressive and pro-fibrotic functions. CCR2(+) monocytic cells are acutely recruited to the lung before the onset of silica-induced fibrosis in mice. These tissue monocytes are defined as monocytic-Myeloid-Derived Suppressor Cells (M-MDSC) because they significantly suppress T lymphocyte proliferation in vitro. M-MDSC collected from silica-treated mice also express TGF-β1, which stimulates lung fibroblasts to release TIMP-1, an inhibitor of metalloproteinase collagenolytic activity...
August 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28798097/suramin-inhibits-osteoarthritic-cartilage-degradation-by-increasing-extracellular-levels-of-chondroprotective-tissue-inhibitor-of-metalloproteinases-3-timp-3
#20
Anastasios Chanalaris, Christine Doherty, Brian D Marsden, Gabriel Bambridge, Stephen P Wren, Hideaki Nagase, Linda Troeberg
Osteoarthritis is a common degenerative joint disease for which no disease-modifying drugs are currently available. Attempts to treat the disease with small molecule inhibitors of the metalloproteinases that degrade the cartilage matrix have been hampered by a lack of specificity. We aimed to inhibit cartilage degradation by augmenting levels of the endogenous metalloproteinase inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP-3), through blocking its interaction with the endocytic scavenger receptor, low-density lipoprotein receptor-related protein 1 (LRP1)...
August 10, 2017: Molecular Pharmacology
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