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Ruiting Lin, Siyuan Xia, Changliang Shan, Dong Chen, Yijie Liu, Xue Gao, Mei Wang, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Michael Rossi, Ragini R Kudchadkar, David H Lawson, Fadlo R Khuri, Sagar Lonial, Jing Chen
Dietary supplements such as vitamins and minerals are widely used in the hope of improving health but may have unidentified risks and side effects. In particular, a pathogenic link between dietary supplements and specific oncogenes remains unknown. Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors...
March 15, 2018: Molecular Cell
Brett Ronald Cutler, Samira Gholami, Jie Shi Chua, Balagurunathan Kuberan, Pon Velayutham Anandh Babu
BACKGROUND: Glycosaminoglycan (GAG), a major component of the endothelial glycocalyx, is severely perturbed in diabetic vasculature leading to endothelial inflammation and vascular disease in diabetes. We tested the hypothesis that blueberry metabolites (BBM) ameliorate endothelial inflammation in diabetic endothelial cells (ECs) by restoring cell surface GAGs. METHODS: ECs isolated from healthy individuals [human aortic ECs (HAECs)] and diabetic patients (diabetic HAECs) were treated with ±BBM (benzoic acid-4-sulfate, hippuric acid, hydroxyhippuric acid, isovanillic acid-3-sulfate, and vanillic acid-4-sulfate at concentrations known to circulate in human plasma following blueberry consumption) for 3 days, and indices for endothelial inflammation were measured...
March 8, 2018: International Journal of Cardiology
Antonio Junior Lepedda, Gabriele Nieddu, Silvia Rocchiccioli, Nadia Ucciferri, Michela Idini, Pierina De Muro, Marilena Formato
Background: Diabetes mellitus is a global health problem representing the fifth leading cause of mortality and a major risk factor for cardiovascular diseases. In the last years, we reported an association among urinary trypsin inhibitor (UTI), a small proteoglycan that plays pleiotropic roles in many inflammatory processes, and both type 1 and 2 diabetes and developed a method for its direct quantitation and structural characterization. Methods: Urine from 39 patients affected by type 1 diabetes, 32 patients with type 2 diabetes, and 52 controls were analysed...
2018: Journal of Diabetes Research
Valeryi K Lishko, Valentin P Yakubenko, Tatiana P Ugarova, Nataly P Podolnikova
Platelet Factor 4 (PF4) is one of the most abundant cationic proteins secreted from α-granules of activated platelets. Based on its structure, PF4 was assigned to the CXC family of chemokines and has been shown to have numerous effects on myeloid leukocytes. However, the receptor for PF4 remains unknown. Here, we demonstrate that PF4 induces leukocyte responses through the integrin Mac-1 (αM β2 , CD11b/CD18). Human neutrophils, monocytes, U937 monocytic and HEK293 cells expressing Mac-1 strongly adhered to immobilized PF4 in a concentration-dependent manner...
March 14, 2018: Journal of Biological Chemistry
Mao Li, Stefanie Mosel, Shirley K Knauer, Carsten Schmuck
Herein, we report a rather simple strategy to enhance the anion binding ability of a dipeptide to achieve cell uptake and also protein delivery. Peptide 1, composed of only two synthetic amino acids with an artificial anion binding site in the side chains, has an overall molecular weight of only 630 Da and demonstrated strong binding affinity (107 M-1 ) and clustering ability with heparin as a model for cell surface sugars. Furthermore, peptide 1 is also efficiently taken up by cells most likely via endocytosis...
March 14, 2018: Organic & Biomolecular Chemistry
Sara Žigon-Branc, Ariana Barlič, Miomir Knežević, Matjaž Jeras, Gordana Vunjak-Novakovic
Inflammation plays a major role in progression of rheumatoid arthritis (RA), a disease treated with antagonists of tumor necrosis factor-alpha (TNF-α) and interleukin 1ß (IL-1ß). New in vitro testing systems are needed to evaluate efficacies of new anti-inflammatory biological drugs, ideally in a patient-specific manner. To address this need, we studied microspheroids containing 10,000 human osteoarthritic primary chondrocytes (OACs) or chondrogenically differentiated mesenchymal stem cells (MSCs), obtained from three donors...
March 14, 2018: Biotechnology Progress
Yuya Otsuka, Toshinori Sato
The structures and amounts of glycosaminoglycan (GAG) produced by cells have attracted much interest because GAG biosynthesis activity can change in cellular processes such as disease and differentiation. β-Xylosides, also called saccharide primers, have been used as artificial acceptors not only to generate GAG oligosaccharides in cells and tissues but also to investigate their biosynthetic pathways. Various analytical methods have been applied to confirm the structure and amounts of GAG oligosaccharides elongated using saccharide primers, yet sample preparation processes such as solid-phase-extraction in analysis can cause experimental error and disrupt accurate comparative quantification of glycosylated products...
March 13, 2018: Analytical Chemistry
Pattana Jaroenlak, Dominic Wiredu Boakye, Rapeepun Vanichviriyakit, Bryony A P Williams, Kallaya Sritunyalucksana, Ornchuma Itsathitphaisarn
BACKGROUND: The microsporidian Enterocytozoon hepatopenaei (EHP) is a spore-forming, intracellular parasite that causes an economically debilitating disease (hepatopancreatic microsporidiosis or HPM) in cultured shrimp. HPM is characterized by growth retardation and wide size variation that can result in economic loss for shrimp farmers. Currently, the infection mechanism of EHP in shrimp is poorly understood, especially at the level of host-parasite interaction. In other microsporidia, spore wall proteins have been reported to be involved in host cell recognition...
March 12, 2018: Parasites & Vectors
Grace Lu, Cassandra L Crihfield, Srikanth Gattu, Lindsay M Veltri, Lisa A Holland
Capillary electrophoresis has emerged as a powerful approach for carbohydrate analyses since 2014. The method provides high resolution capable of separating carbohydrates by charge-to-size ratio. Principle applications are heavily focused on N-glycans, which are highly relevant to biological therapeutics and biomarker research. Advances in techniques used for N-glycan structural identification include migration time indexing and exoglycosidase and lectin profiling, as well as mass spectrometry. Capillary electrophoresis methods have been developed that are capable of separating glycans with the same monosaccharide sequence but different positional isomers, as well as determining whether monosaccharides composing a glycan are alpha or beta linked...
March 12, 2018: Chemical Reviews
Agata Zykwinska, Ludivine Tripon-Le Berre, Corinne Sinquin, David Ropartz, Hélène Rogniaux, Sylvia Colliec-Jouault, Christine Delbarre-Ladrat
Polysaccharides have attracted much attention due to their interesting physico-chemical and also biological properties that are explored in food, cosmetic and pharmaceutical industries. GY785 exopolysaccharide (EPS) presenting an unusual structure is secreted by the deep-sea hydrothermal bacterium, Alteromonas infernus. Low-molecular weight (LMW) derivatives obtained by chemical depolymerization of the native high molecular weight (HMW) EPS were previously shown to exhibit biological properties similar to glycosaminoglycans (GAG)...
May 15, 2018: Carbohydrate Polymers
Rafael S Aquino, Yvonne Hui-Fang Teng, Pyong Woo Park
Syndecan-1 (Sdc1) is a major cell surface heparan sulfate (HS) proteoglycan of epithelial cells, a cell type targeted by many bacterial pathogens early in their pathogenesis. Loss of Sdc1 in mice is a gain-of-function mutation that significantly decreases the susceptibility to several bacterial infections, suggesting that subversion of Sdc1 is an important virulence strategy. HS glycosaminoglycan (GAG) chains of cell surface Sdc1 promote bacterial pathogenesis by facilitating the attachment of bacteria to host cells...
March 9, 2018: Biochemical Society Transactions
Wei Duan, Cong Chen, Masudul Haque, Daniel Hayes, Mandi J Lopez
BACKGROUND: Use of bioscaffolds to direct osteogenic differentiation of adult multipotent stromal cells (MSCs) without exogenous proteins is a contemporary approach to bone regeneration. Identification of in vivo osteogenic contributions of exogenous MSCs on bioscaffolds after long-term implantation is vital to understanding cell persistence and effect duration. METHODS: This study was designed to quantify in vivo equine MSC osteogenesis on synthetic polymer scaffolds with distinct mineral combinations 9 weeks after implantation in a murine model...
March 9, 2018: Stem Cell Research & Therapy
Mohammad-Hossein Beigi, Atefeh Atefi, Hamid-Reza Ghanaei, Sheyda Labbaf, Fatemeh Ejeian, Mohammad-Hossein Nasr-Esfahani
In the current study the effect of superimposing platelet-rich plasma (PRP) on different culture mediums in a three-dimensional (3D) alginate scaffold encapsulated with adipose mesenchymal stem cells (ADSCs) for cartilage tissue repair is reported. The 3D alginate scaffolds with co-administration of PRP and/or chondrogenic supplements had a significant effect on the differentiation of ADSCs into mature cartilage, as assessed by evaluation of the expression of cartilage related markers of Sox9, Collagen II, Aggrecan and collagen and glycosaminoglycan assays...
March 9, 2018: Journal of Tissue Engineering and Regenerative Medicine
Shreyasi Asthana, Bibekanand Mallick, Andrei T Alexandrescu, Suman Jha
Islet amyloid polypeptide (a.k.a. IAPP, amylin) is a 37 amino acid hormone that has long been associated with the progression of type II diabetes mellitus (TIIDM) disease. The endocrine peptide hormone aggregatively misfolds to form amyloid deposits in and around the pancreatic islet β-cells that synthesize both insulin and IAPP, leading to a decrease in β-cell mass in patients with the disease. Extracellular IAPP amyloids induce β-cell death through the formation of reactive oxygen species, mitochondrial dysfunction, chromatin condensation, and apoptotic mechanisms, although the precise roles of IAPP in TIIDM are yet to be established...
March 5, 2018: Biochimica et Biophysica Acta
Yung-Ching Chen, King-Chuen Wu, Bu-Miin Huang, Edmund Cheung So, Yang-Kao Wang
Midazolam, a benzodiazepine derivative, is widely used for sedation and surgery. However, previous studies have demonstrated that Midazolam is associated with increased risks of congenital malformations, such as dwarfism, when used during early pregnancy. Recent studies have also demonstrated that Midazolam suppresses osteogenesis of mesenchymal stem cells (MSCs). Given that hypertrophic chondrocytes can differentiate into osteoblast and osteocytes and contribute to endochondral bone formation, the effect of Midazolam on chondrogenesis remains unclear...
March 7, 2018: Journal of Cellular and Molecular Medicine
Yan Wen, Ping Li, Jingcan Hao, Chen Duan, Jing Han, Awen He, Yanan Du, Li Liu, Xiao Liang, Feng Zhang, Xiong Guo
BACKGROUND: Kashin-Beck disease (KBD) is an endemic osteochondropathy of unknown etiology. Osteoarthritis (OA) is a form of degenerative joint disease sharing similar clinical manifestations and pathological changes to articular cartilage with KBD. METHODS: A genome-wide DNA methylation profile of articular cartilage from five KBD patients and five OA patients was first performed using the Illumina Infinium HumanMethylation450 BeadChip. Together with a previous gene expression profiling dataset comparing KBD cartilage with OA cartilage, an integrative pathway enrichment analysis of the genome-wide DNA methylation and the mRNA expression profiles conducted in articular cartilage was performed by InCroMAP software...
March 7, 2018: Arthritis Research & Therapy
Nancy B Schwartz, Miriam S Domowicz
Proteoglycans are diverse, complex extracellular/cell surface macromolecules composed of a central core protein with covalently-linked glycosaminoglycan (GAG) chains; both of these components contribute to the growing list of important bio-active functions attributed to proteoglycans. Increasingly, attention has been paid to the roles of proteoglycans in nervous tissue development due to their highly regulated spatio/temporal expression patterns, whereby they promote/inhibit neurite outgrowth, participate in specification and maturation of various precursor cell types, and regulate cell behaviors like migration, axonal pathfinding, synaptogenesis, and plasticity...
March 7, 2018: FEBS Letters
Yasar Hoosen, Priyamvada Pradeep, Pradeep Kumar, Lisa C du Toit, Yahya E Choonara, Viness Pillay
Ovarian cancer (OC) has gained a great deal of attention due to its aggressive proliferative capabilities, high death rates and poor treatment outcomes, rendering the disease the ultimate lethal gynaecological cancer. Nanotechnology provides a promising avenue to combat this malignancy by the niche fabrication of optimally-structured nanomedicines that ensure potent delivery of chemotherapeutics to OC, employing nanocarriers to act as "intelligent" drug delivery vehicles, functionalized with active targeting approaches for precision delivery of chemotherapeutics to overexpressed biomarkers on cancer cells...
March 4, 2018: International Journal of Molecular Sciences
Lilla Turiák, Gábor Tóth, Oliver Ozohanics, Ágnes Révész, András Ács, Károly Vékey, Joseph Zaia, László Drahos
A simple, isocratic HPLC method based on HILIC-WAX separation, has been developed for analyzing sulfated disaccharides of glycosaminoglycans (GAGs). To our best knowledge, this is the first successful attempt using this special phase in nano-HPLC-MS analysis. Mass spectrometry was based on negative ionization, improving both sensitivity and specificity. Detection limit for most sulfated disaccharides were approximately 1 fmol; quantitation limits 10 fmol. The method was applied for glycosaminoglycan profiling of tissue samples, using surface digestion protocols...
February 25, 2018: Journal of Chromatography. A
Erin L Stephenson, Manoj K Mishra, Daniel Moussienko, Nataly Laflamme, Serge Rivest, Chang-Chun Ling, V Wee Yong
Multiple sclerosis presents with profound changes in the network of molecules involved in maintaining central nervous system architecture, the extracellular matrix. The extracellular matrix components, particularly the chondroitin sulfate proteoglycans, have functions beyond structural support including their potential interaction with, and regulation of, inflammatory molecules. To investigate the roles of chondroitin sulfate proteoglycans in multiple sclerosis, we used the experimental autoimmune encephalomyelitis model in a time course study...
March 1, 2018: Brain: a Journal of Neurology
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