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Sebastian Köhling, Joanna Blaszkiewicz, Gloria Ruiz-Gómez, María Isabel Fernández-Bachiller, Katharina Lemmnitzer, Nydia Panitz, Annette G Beck-Sickinger, Jürgen Schiller, M Teresa Pisabarro, Jörg Rademann
Binding of sulfated glycosaminoglycans (GAG) to a wide spectrum of extracellular regulatory proteins is crucial for physiological processes such as cell growth, migration, tissue homeostasis and repair. Thus, GAG derivatives exhibit great relevance in the development of innovative biomaterials for tissue regeneration therapies. We present a synthetic strategy for the preparation of libraries of defined sulfated oligohyaluronans as model GAG systematically varied in length, sulfation pattern and anomeric substitution in order to elucidate the effects of these parameters on GAG recognition by regulatory proteins...
January 21, 2019: Chemical Science
Rim Serhal, Nagib Saliba, George Hilal, Mayssam Moussa, Ghada S Hassan, Oula El Atat, Nada Alaaeddine
AIM: To investigate the effect of adipose-derived mesenchymal stem cells (ADMSCs) and their conditioned media (CM) on hepatocellular carcinoma (HCC) cell tumorigenesis. METHODS: The proliferation rate of HepG2 and PLC-PRF-5 HCC cancer cells was measured using the trypan blue exclusion method and confirmed using the cell-counting kit 8 (commonly known as CCK-8) assay. Apoptosis was detected by flow cytometry using annexin V-FITC. Protein and mRNA expression was quantified by ELISA and real time PCR, respectively...
February 7, 2019: World Journal of Gastroenterology: WJG
Jae Han Ko, Young Mi Kang, Jae Ho Yang, Ji Sup Kim, Won Jai Lee, Sang Ho Kim, Ick Hwan Yang, Seong Hwan Moon
PURPOSE: The aim of this study was to investigate the effects of relaxin (RLN) expression on fibrosis inhibition in synovial fibroblasts. MATERIALS AND METHODS: Tissue cells from patients with knee osteoarthritis and >30° flexion contractures were utilised. Synovial fibroblasts were activated by TGF-β1 (two nanograms per millilitre) and then exposed to Ad-RLN as a therapeutic gene, adenovirus-lacZ construct as a marker gene, and SB505124 as an inhibitor for TGF-β1 signal for 48 h...
February 13, 2019: Knee
Dae Woo Kim, Kyoung Mi Eun, Eun Youn Roh, Sue Shin, Dong-Kyu Kim
Chronic rhinosinusitis (CRS) shows heterogeneous immunologic features. Western studies revealed that CRS without nasal polyps (CRSsNP) showed a predominantly type 1 immune response and CRS with nasal polyps (CRSwNP) was characterized by type 2 immune response; however, the detailed immunologic profile of CRSsNP in Asian patients has not been thoroughly investigated. Therefore, we investigated the inflammatory endotypes of CRSsNP in Asian patients. Patients with CRSsNP ( N = 57), patients with CRSwNP ( N = 13), and a control group ( N = 10), who underwent endoscopic sinus surgery, were enrolled; uncinate process (UP) tissues were harvested from all patients...
2019: Mediators of Inflammation
Jonathan H Soslow, Meng Xu, James C Slaughter, Kimberly Crum, Joshua D Chew, W Bryan Burnette, Yan Ru Su, Kelsey Tomasek, David A Parra, Larry W Markham
BACKGROUND: Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Standard cardiac biomarkers are poor indicators of DMD cardiovascular disease. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate collagen turnover. Given the cardiac fibrosis seen in DMD, we hypothesized that MMPs and TIMPs correlate with severity of DMD cardiomyopathy. METHODS AND RESULTS: Prospectively enrolled DMD subjects (n=42) underwent cardiac MRI for function and late gadolinium enhancement (LGE), including LGE severity from 0 (no LGE) to 4 (severe)...
February 11, 2019: Journal of Cardiac Failure
Felix Nagel, David Santer, Stefan Stojkovic, Christoph Kaun, Anne-Kristin Schaefer, Martin Kššák, Dietmar Abraham, Péter Bencsik, Péter Ferdinandy, Eva Kenyeres, Tamara Szabados, Johann Wojta, Karola Trescher, Attila Kiss, Bruno K Podesser
The aim of this study was to describe the potential associations of the expression of matricellular components in adverse post-infarction remodeling of the geriatric heart. In male geriatric (OM, age: 18 months) and young (YM, age: 11 weeks) OF1 mice myocardial infarction (MI) was induced by permanent ligation of the left anterior descending coronary artery. Cardiac function was evaluated by MRI. Plasma and myocardial tissue samples were collected 3d, 7d, and 32d post-MI. Age and MI were associated with impaired cardiac function accompanied by left-ventricular (LV) dilatation...
February 11, 2019: Experimental Gerontology
Diego Pulzatto Cury, Bárbara Tavares Schäfer, Sonia Regina Yokomizo de Almeida, Marta Maria da Silva Righetti, Ii-Sei Watanabe
BACKGROUND: The prolonged tendon-healing process, the high costs associated with treatment, the increase in the number of injuries over the past decades, and the lack of consensus on the optimal treatment of tendon injuries are a global problem. Restoring the normal tendon anatomy and decreasing the healing time are key factors for treatment advancement. HYPOTHESIS: Application of a purified protein from natural latex (PPNL) accelerates the healing process, increasing collagen synthesis and decreasing metalloproteinases...
February 13, 2019: American Journal of Sports Medicine
Chase Thorson, Kevin Galicia, Andrew Burleson, Olivia Bouchard, Debra Hoppensteadt, Jawed Fareed, William Hopkinson
Osteoarthritis, a degenerative disease of the joints, is the most common form of arthritis in the knee. Total joint arthoplasty is a commonly used treatment for joint degeneration and osteoarthritis, and due to these factors, TJA for hip and knee joints is projected to grow by 137% and 601% between 2005 and 2030. Matrix metalloproteases are enzymes found in the extracellular matrix that cleave matrix components. Normally MMPs are downregulated in tissues by Tissue Inhibitors of Metalloproteases, or TIMPs. The relative concentration of TIMPs also may denote some of the activity of the MMPs found in serum...
January 2019: Clinical and Applied Thrombosis/hemostasis
Yifan Joshua Li, Katalin A Wilkinson, Robert J Wilkinson, Anthony A Figaji, Ursula K Rohlwink
We collected lumbar and ventricular cerebrospinal fluid and serum from 40 children treated for tuberculous meningitis and measured the concentrations of gelatinases and their inhibitors. The concentrations of matrix metalloproteinase 9 (MMP-9), MMP-2, tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2 were significantly elevated in the lumbar CSF samples, and we found interesting dynamics for MMP-9 that offer novel insight into its role in pediatric patients with tuberculous meningitis.
February 12, 2019: Journal of the Pediatric Infectious Diseases Society
Quang T Nguyen, Mohamed Jalloul Nsaibia, Martin G Sirois, Angelino Calderone, Jean-Claude Tardif, Yan Fen Shi, Matthieu Ruiz, Caroline Daneault, Lyne Gagnon, Brigitte Grouix, Pierre Laurin, Jocelyn Dupuis
Aims: Heart failure with reduced ejection fraction (HFrEF) causes lung remodelling with myofibroblasts proliferation and fibrosis leading to a restrictive lung syndrome with pulmonary hypertension (PH) and right ventricular (RV) dysfunction. PBI-4050 is a first-in-class anti-fibrotic, anti-inflammatory and anti-proliferative compound. The present study evaluated the therapeutic impact of PBI-4050 on PH in an HFrEF model. Methods and Results: HFrEF was induced after myocardial infarction (MI) in rats...
February 7, 2019: Cardiovascular Research
Sina Waldherr, Alexander Fichtner, Bernd Beedgen, Thomas Bruckner, Franz Schaefer, Burkhard Tönshoff, Johannes Pöschl, Timm H Westhoff, Jens H Westhoff
BACKGROUND: Serum creatinine (SCr)- or urine output-based definitions of acute kidney injury (AKI) have important limitations in neonates. This study evaluates the diagnostic value of urinary biomarkers in very low-birth-weight (VLBW) infants receiving indomethacin for closure of a patent ductus arteriosus (PDA). METHODS: Prospective cohort study in 14 indomethacin-treated VLBW infants and 18 VLBW infants without indomethacin as controls. Urinary biomarkers were measured before, during, and after indomethacin administration...
February 11, 2019: Pediatric Research
Philippe Grieshaber, Sina Möller, Borros Arneth, Peter Roth, Bernd Niemann, Harald Renz, Andreas Böning
BACKGROUND:  Prediction, early diagnosis, and therapy of cardiac surgery-associated acute kidney injury (CSA-AKI) are challenging. We prospectively tested a staged approach to identify patients at high risk for CSA-AKI combining clinical risk stratification and early postoperative quantification of urinary biomarkers for AKI. METHODS:  All patients, excluding those on chronic hemodialysis, undergoing scheduled surgery with cardiopulmonary bypass between August 2015 and July 2016 were included...
February 11, 2019: Thoracic and Cardiovascular Surgeon
Liyao Lin, Keluo Cheng, Zhan He, Qiongyan Lin, Yidong Huang, Chunyuan Chen, Zhanqiang Xie, Lin Chen, Zhu Liang
In this study we investigated the potential effects of a polysaccharide (HDP) from Hedyotis diffusa on the metastasis in human lung adenocarcinoma A549 cells. HDP (25, 50 and 100 μg/ml) significantly suppressed the cell adhesion, invasion and migration of A549 cells in a dose dependent manner by downregulation of matrix metalloproteinase (MMP-2 and MMP-9) and upregulation of tissue inhibitors of metalloproteinase (TIMP-2 and TIMP-9). Moreover, HDP effectively downregulated the protein expressions of epithelial-mesenchymal transition (EMT) markers (N-cadherin and vimentin), and upregulated E-cadherin protein expression, which is involved in interrupting EGFR/Akt/ERK signaling pathways, as well as inhibiting COX-2 protein expression...
February 7, 2019: International Journal of Biological Macromolecules
Bo Peng, Rong He, Qihua Xu, Yifei Yang, Qin Hu, Hongping Hou, Xinmin Liu, Jianrong Li
Metastasis is the primary cause of cancer recurrence and cancer related mortality in triple-negative breast cancer (TNBC). EGFR overexpression is in 50-75% TNBC and EGFR-mediated signaling has potential as an attractive therapeutic target in some specific subtypes of breast cancer due to its significant association with tumor metastasis and poor prognosis. Therefore, identification of promising therapeutic strategies targeting EGFR with higher specificity toward cancer metastasis is urgently needed. 20(S)-protopanaxadiol (PPD), one of the major active metabolites from Panax ginseng, has been widely reported to possess pleiotropic anticancer activities in various cancers...
February 5, 2019: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Carin E Ahner, Aaron M Stoker, Chantelle C Bozynski, Cristi R Cook, Emily Leary, Keiichi Kuroki, Carissa N Cruz, James L Cook
This study compares serum and urine concentrations of relevant protein biomarkers among adult dogs with or without radiographic canine hip dysplasia (CHD). Adult (≥ 2 years of age), client-owned dogs (n = 74) radiographically categorized as having at least "good" hips (n = 49) or having "mild", "moderate", or "severe" hip dysplasia (n = 25) by the Orthopedic Foundation for Animals (OFA). Urine and serum samples were obtained from each dog at a single time-point and processed and analyzed for relevant protein biomarkers...
February 5, 2019: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Ji Suk Choi, Woo Lee Cho, Yeo Jin Choi, Jae Dong Kim, Hyun-A Park, Su Yeon Kim, Jae Hyung Park, Dong-Gyu Jo, Yong Woo Cho
Ultraviolet-B (UVB) irradiation causes imbalance between dermal matrix synthesis and degradation through aberrant upregulation of matrix metalloproteinases (MMPs), which leads to overall skin photoaging. We investigated the effects of extracellular vesicles (EVs) derived from human adipose-derived stem cells (HASCs) on photo-damaged human dermal fibroblasts (HDFs). EVs were isolated from conditioned media of HASCs with tangential flow filtration and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), western blotting, micro RNA (miRNA) arrays, cytokine arrays and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)...
2019: Journal of Extracellular Vesicles
Marta Łukaszewicz-Zając, Mariusz Gryko, Sara Pączek, Maciej Szmitkowski, Bogusław Kędra, Barbara Mroczko
Objectives: The incidence rate of pancreatic cancer (PC) is similar to mortality rate, thus searching specific tumor biomarkers of PC is sorely needed. Matrix metalloproteinase-2 (MMP-2) and the imbalance between MMP-2 and its tissue inhibitor (TIMP-2) play a critical role in tumor progression. We aim to assess the diagnostic and prognostic usefulness of serum MMP-2 and TIMP-2 as potential biomarkers in comparison to well-established tumor markers of PC (CA 19-9, carbohydrate antigen 19-9 and CEA, carcinoembryonic antigen)...
January 8, 2019: Oncotarget
J Dinesh Kumar, Iman Aolymat, Laszlo Tiszlavicz, Zita Reisz, Hanan M Garalla, Rob Beynon, Deborah Simpson, Graham J Dockray, Andrea Varro
The chemokine-like peptide, chemerin, stimulates chemotaxis in several cell types. In this study we examined the expression of putative chemerin receptors in gastric cancer and the action of chemerin on cancer cell migration and invasion. Immunohistochemical studies of gastric tumors identified expression of two putative receptors, chemokine-like receptor-1 (CMKLR1) and G-protein coupled receptor 1(GPR1), in cancer cells; there was also some expression in stromal myofibroblasts although generally at a lower intensity...
January 4, 2019: Oncotarget
Yaqin Jiang, Canwei Zhang, Jianli Ma, Luping Wang, Jing Gao, Jiantao Ren, Wei He, Sheng Wang, Shuai Sheng, Xudong Huang
BACKGROUND: To investigate the expression of Matrix Metalloproteinases 2 and aquaporin-1 in corneoscleral junction and explore the mechanism of trabecular damageafter angle-closure. METHODS: Thirty New Zealand white rabbits were randomly assigned into 2 groups, theexperimental group (Group 1) including twenty five rabbits and the control group (Group 2) including 5 rabbits. The rabbits in the experimental group were used to establish angle-closure models, and the rabbits in the control group were not subjected to any operation...
February 4, 2019: BMC Ophthalmology
Yuanjian Chen, Wenyuan Zhao, Chang Liu, Weixin Meng, Tieqiang Zhao, Syamal K Bhattacharya, Yao Sun
Background: Studies implicate that Ang1-7 imparts protective effects in the kidney. However, its relevance in hypertensive kidney disease is not fully understood. The purpose of this study is to explore the role of Ang1-7 on renal damage/remodeling during hypertension and its potential underlying molecular-cellular mechanisms. Methods: Hypertension was induced in adult Sprague Dawley rats by infusion of ALDO (0.75μg/h) for 4 weeks with or without co-treatment of Ang1-7 (1mg/kg/day)...
January 29, 2019: American Journal of Hypertension
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