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https://www.readbyqxmd.com/read/28224786/cisplatin-crosslinked-multifunctional-nanodrugplexes-for-combination-therapy
#1
Weiqi Zhang, Ching-Hsuan Tung
Combination therapy efficiently tackles cancer by hitting multiple action mechanisms. However, drugs administered, simultaneously or sequentially, may not reach the targeted sites with the desired dose and ratio. The outcomes of combination therapy could be improved with a polymeric nanoparticle, which can simultaneously transport an optimal combination of drugs. We have demonstrated a simple one-pot strategy to formulate nanomedicines based on platinum coordination and the non-covalent interactions of the drugs...
February 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28222208/effect-of-thiolated-glycosaminoglycans-on-the-behavior-of-breast-cancer-cells-toward-the-development-of-in-vitro-models-of-cancer
#2
Alexander Köwitsch, Ankur Chhalotre, Thomas Groth
PURPOSE: The influence of extracellular matrix components like glycosaminoglycans (GAG) or adhesive proteins on the migration of cancer cells and the progression of tumorigenesis remains a challenging task. Therefore, this study aims to give insight into the interaction of cancer cells exhibiting different metastatic potential (MDA-MB-231, MDA-MB-468) with surface immobilized GAG interacting with serum proteins like fibronectin. METHODS: Model substrata were covalently coated with different thiolated GAG (hyaluronan (HA), chondroitin sulfate (CS), heparin (Hep)) and investigated for the adsorption of fibronectin (FN) with surface plasmon resonance...
February 18, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28217782/receptor-for-hyaluronan-mediated-motility-rhamm-hmmr-is-a-novel-target-for-promoting-subcutaneous-adipogenesis
#3
S B Bahrami, C Tolg, T Peart, C Symonette, M Veiseh, J U Umoh, D W Holdsworth, J B McCarthy, L G Luyt, M J Bissell, A Yazdani, E A Turley
Hyaluronan, CD44 and the Receptor for Hyaluronan-Mediated Motility (RHAMM, gene name HMMR) regulate stem cell differentiation including mesenchymal progenitor differentiation. Here, we show that CD44 expression is required for subcutaneous adipogenesis, whereas RHAMM expression suppresses this process. We designed RHAMM function blocking peptides to promote subcutaneous adipogenesis as a clinical and tissue engineering tool. Adipogenic RHAMM peptides were identified by screening for their ability to promote adipogenesis in culture assays using rat bone marrow mesenchymal stem cells, mouse pre-adipocyte cell lines and primary human subcutaneous pre-adipocytes...
February 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28214837/efficacy-of-glucosamine-sulphate-in-skin-ageing-results-from-an-ex-vivo-anti-ageing-model-and-a-clinical-trial
#4
Audrey Gueniche, Isabelle Castiel-Higounenc
BACKGROUND: Glucosamine sulphate (GS) is essential in the biosynthesis of glycolipids, glycoproteins, glycosaminoglycans (GAGs), hyaluronate, and proteoglycans. Connective tissues primarily contain collagen and proteoglycans and play an important role in skin ageing. OBJECTIVE: The objectives were to assess ex vivo the impact of GS on skin ageing parameters and in vivo the effect of GS on the skin physiology of mature healthy volunteers after oral intake. METHODS: The impact of GS on skin ageing was assessed ex vivo via different immunohistochemical assays and histology and via a clinical study using biopsies...
February 18, 2017: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/28211875/a-hyaluronan-hydrogel-scaffold-based-xeno-free-culture-system-for-ex-vivo-expansion-of-human-corneal-epithelial-stem-cells
#5
D Chen, Y Qu, X Hua, L Zhang, Z Liu, S C Pflugfelder, D-Q Li
PurposeTo develop a hyaluronan hydrogel scaffold-based xeno-free culture system for ex vivo cultivation of human corneal epithelial stem cells (CESCs).Patients and MethodsCESCs were cultivated from donor limbal explants on the HyStem-C Hydrogel bio-scaffold in 12-well plates for 3 weeks. Group A used the traditional supplemented hormonal epidermal medium (SHEM) and group B used the defined SHEM (without fetal bovine serum and toxin A, adding 20% serum replacement). The growth and morphology of the cultured cells were assessed by phase contrast microscope...
February 17, 2017: Eye
https://www.readbyqxmd.com/read/28207787/hyaluronic-acid-synthesis-is-required-for-zebrafish-tail-fin-regeneration
#6
Xiaohu Ouyang, Nicholas J Panetta, Maya D Talbott, Alexander Y Payumo, Caroline Halluin, Michael T Longaker, James K Chen
Using genome-wide transcriptional profiling and whole-mount expression analyses of zebrafish larvae, we have identified hyaluronan synthase 3 (has3) as an upregulated gene during caudal fin regeneration. has3 expression is induced in the wound epithelium within hours after tail amputation, and its onset and maintenance requires fibroblast growth factor, phosphoinositide 3-kinase, and transforming growth factor-ß signaling. Inhibition of hyaluronic acid (HA) synthesis by the small molecule 4-methylumbelliferone (4-MU) impairs tail regeneration in zebrafish larvae by preventing injury-induced cell proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28202328/discovery-of-hyaluronidase-inhibitors-from-natural-products-and-their-mechanistic-characterization-under-dmso-perturbed-assay-conditions
#7
Keisuke Tomohara, Tomohiro Ito, Saika Onikata, Atsushi Kato, Isao Adachi
The present study discovered four novel hyaluronan-degrading enzyme (hyaluronidase) inhibitors including chikusetsusaponins and catechins through the activity-guided separation of Panax japonicus and Prunus salicina, respectively. Although the discovery resulted in identification of usual frequent hitters, subsequent mechanistic characterizations under our DMSO-perturbed assay conditions and related protocols revealed that chikusetusaponin IV would serve as an aggregating and non-specific binding inhibitor, while (-)-epicatechin would interact specifically with enzyme at the catalytic site or more likely at a kind of catechin-binding site with a relatively week inhibitory activity...
January 31, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28196904/extracellular-matrix-receptor-expression-in-subtypes-of-lung-adenocarcinoma-potentiates-outgrowth-of-micrometastases
#8
Laura E Stevens, William Kc Cheung, Sally J Adua, Anna Arnal-Estapé, Minghui Zhao, Zongzhi Liu, Kelly Brewer, Roy S Herbst, Don X Nguyen
Mechanisms underlying the propensity of latent lung adenocarcinoma (LUAD) to relapse are poorly understood. In this study, we show how differential expression of a network of extracellular matrix (ECM) molecules and their interacting proteins contributes to risk of relapse in distinct LUAD subtypes. Overexpression of the hyaluronan receptor HMMR in primary LUAD was associated with an inflammatory molecular signature and poor prognosis. Attenuating HMMR in LUAD cells diminished their ability to initiate lung tumors and distant metastases...
February 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28196902/hyaluronidase-2-deficiency-causes-increased-mesenchymal-cells-congenital-heart-defects-and-heart-failure
#9
Biswajit Chowdhury, Bo Xiang, Michelle Liu, Richard Hemming, Vernon W Dolinsky, Barbara Triggs-Raine
BACKGROUND: Hyaluronan (HA) is required for endothelial-to-mesenchymal transition and normal heart development in the mouse. Heart abnormalities in hyaluronidase 2 (HYAL2)-deficient (Hyal2(-)(/-) ) mice and humans suggested removal of HA is also important for normal heart development. We have performed longitudinal studies of heart structure and function in Hyal2(-/-) mice to determine when, and how, HYAL2 deficiency leads to these abnormalities. METHODS AND RESULTS: Echocardiography revealed atrial enlargement, atrial tissue masses, and valvular thickening at 4 weeks of age, as well as diastolic dysfunction that progressed with age, in Hyal2(-/-) mice...
January 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28192668/key-role-of-the-carboxyl-terminus-of-hyaluronan-synthase-in-processive-synthesis-and-size-control-of-hyaluronic-acid-polymers
#10
Ji Yang, Fangyu Cheng, Huimin Yu, Junting Wang, Guo Zhi Gang, Gregory Stephanopoulos
The essential pathophysiological roles of hyaluronic acid (HA) strongly depend on HA binding and HA size. Here we deployed the atomic vision of molecular dynamics (MD) simulation to experimentally investigate the influence of C-terminal mutations of Streptococcus equisimilis hyaluronan synthase (SeHAS) on HA product synthesis in Escherichia coli. R413 was vital for HA production, as the removal or mutation of R413 led to inactivation of SeHAS. MD simulations indicated that R406-R413 constituted an HA-binding pattern that stabilized the HA-SeHAS complex...
February 13, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28188289/human-keratinocytes-respond-to-extracellular-utp-by-induction-of-hyaluronan-synthase-2-expression-and-increased-hyaluronan-synthesis
#11
Tiina A Jokela, Riikka Kärnä, Leena Rauhala, Genevieve Bart, Sanna Pasonen-Seppänen, Sanna Oikari, Markku I Tammi, Raija H Tammi
The release of nucleotides into extracellular space is triggered by insults like wounding and ultraviolet radiation, resulting in stimulatory or inhibitory signals via plasma membrane nucleotide receptors. As similar insults are known to activate hyaluronan synthesis we explored the possibility that extracellular UTP or its breakdown products UDP and UMP act as mediators for hyaluronan synthase (HAS) activation in human epidermal keratinocytes. UTP increased hyaluronan both in the pericellular matrix and in the culture medium of HaCaT cells...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28183614/evaluation-of-cell-surface-interaction-using-a-3d-spheroid-cell-culture-model-on-artificial-extracellular-matrices
#12
Wolfgang Metzger, Sandra Rother, Tim Pohlemann, Stephanie Möller, Matthias Schnabelrauch, Vera Hintze, Dieter Scharnweber
Since decades, cell-surface interactions are studied in 2D cell culture approaches, but cells organized in 3D (spheroids) reflect the normal situation of cells in tissues much better due to intense cell-cell-contacts. Accordingly, this study aimed to prove, if spheroids could be used to study cell-surface interaction. Spheroids consisting of fibroblasts and/or osteoblasts were seeded on artificial extracellular matrices. Here, non-sulfated hyaluronan as a biological relevant compound of the extracellular matrix was chemically sulfated to different extents and co-fibrillised with collagen...
April 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28181464/physicochemical-characterization-of-chitosan-hyaluronan-coated-solid-lipid-nanoparticles-for-the-targeted-delivery-of-paclitaxel-a-proof-of-concept-study-in-breast-cancer-cells
#13
Javier Campos, Manuel Varas-Godoy, Ziyad Samir Haidar
AIM: To investigate the potential of modified solid lipid nanoparticles (SLN) for the delivery of paclitaxel (PAX). MATERIALS & METHODS: SLN loaded with PAX were prepared via modified high-pressure hot homogenization. Formulation parameters were optimized to obtain a high-quality delivery system. SLN cores were coated, layer-by-layer, with a chitosan and hyaluronan (HA) shell. Selectivity toward HA receptors was tested in a breast cancer cell line, MCF-7. RESULTS: Stable and reproducible nano-sized and negatively charged nanoparticles resulted...
February 9, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28179576/kiaa1199-is-induced-by-inflammation-and-enhances-malignant-phenotype-in-pancreatic-cancer
#14
Shiro Kohi, Norihiro Sato, Atsuhiro Koga, Nobutaka Matayoshi, Keiji Hirata
BACKGROUND: Recent evidence suggests a critical role of hyaluronan (HA), especially low-molecular-weight HA (LMW-HA), in the aggressive tumor phenotype. Increased expression of KIAA1199, a newly identified protein involved in HA degradation, has been reported in various cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the functional significance of KIAA1199 in PDAC. METHODS: Using siRNA knockdown and forced expression models, we investigated the effects of KIAA1199 expression on malignant behaviors (proliferation, migration, and invasion) of PDAC cells...
February 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176896/paclitaxel-loaded-hyaluronan-solid-nanoemulsions-for-enhanced-treatment-efficacy-in-ovarian-cancer
#15
Joo-Eun Kim, Young-Joon Park
Paclitaxel-loaded hyaluronan solid nanoemulsions (PTX-HSNs) were successfully fabricated for the delivery of PTX to improve ovarian cancer treatment via active tumor targeting. PTX-HSNs were fabricated using high-pressure homogenization with a microfluidizer and were lyophilized with d-mannitol. Hyaluronan was coated on the outside of the PTX-HSN sphere. The mean size of the PTX-HSNs was maintained less than 100 nm, with a relatively narrow size distribution. The PTX loading content was 3 mg/mL, and encapsulation efficiency (EE) was close to 100%...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28168629/role-of-hyal1-expression-in-primary-breast-cancer-in-the-formation-of-brain-metastases
#16
Isabell Witzel, Anna K Marx, Volkmar Müller, Harriet Wikman, Jakob Matschke, Udo Schumacher, Christine Stürken, Peter Prehm, Elena Laakmann, Barbara Schmalfeldt, Karin Milde-Langosch, Leticia Oliveira-Ferrer
BACKGROUND: The incidence of brain metastases in breast cancer patients has increased in the last years. However, the knowledge about tumor cell invasion in the brain is still very limited. Based on our recent study on cDNA microarray data of breast cancer patients, we hypothesized that two enzymes involved in the hyaluronan metabolism, namely, hyaluronan synthase 2 (HAS2) and hyaluronidase 1 (HYAL1) are associated with brain metastases formation. METHODS: Protein expression levels of hyaluronan, HAS2, and HYAL1 were analyzed in primary breast cancer, and metastatic tissue samples from different localizations (brain, bone, skin, liver, and lung) were included in four different cohorts by immunohistochemistry...
February 6, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28166932/hyaluronan-mediates-the-adhesion-of-porcine-peripheral-blood-mononuclear-cells-to-poly-i-c-treated-intestinal-cells-and-modulates-their-cytokine-production
#17
María José Docampo, Jennifer Cabrera, Anna Bassols
Hyaluronan (HA), a major component of the extracellular matrix (ECM), has been increasingly recognized as a regulator of inflammation. Its role is complex since it has pro- and anti-inflammatory actions by modulating the expression of inflammatory genes, the recruitment of inflammatory cells and the production of inflammatory cytokines, but also by attenuating the course of inflammation and providing protection against tissue damage. Certain viruses and other inflammatory stimuli induce organization of HA into cable-like structures, which may be responsible for leukocyte recruitment and, on the other hand, low molecular weight fragments of HA have been shown to activate various inflammatory responses...
February 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28165063/heavy-chain-hyaluronan-pentraxin-3-from-amniotic-membrane-suppresses-inflammation-and-scarring-in-murine-lacrimal-gland-and-conjunctiva-of-chronic-graft-versus-host-disease
#18
Yoko Ogawa, Hua He, Shin Mukai, Toshihiro Imada, Shigeru Nakamura, Chen-Wei Su, Megha Mahabole, Scheffer C G Tseng, Kazuo Tsubota
Chronic graft-versus-host disease (cGVHD) is a major complication of hematopoietic stem cell transplantation. Dry eye disease is the prominent ocular sequel of cGVHD and is caused by excessive inflammation and fibrosis in the lacrimal glands. Heavy chain-Hyaluronan/Pentraxin 3 (HC-HA/PTX3) is a complex purified from human amniotic membrane (AM) and known to exert anti-inflammatory and anti-scarring actions. In this study, we utilized a mouse model of cGVHD to examine whether HC-HA/PTX3 could attenuate dry eye disease elicited by cGVHD...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28163228/a-novel-in-situ-silver-hyaluronan-bio-nanocomposite-fabrics-for-wound-and-chronic-ulcer-dressing-in-vitro-and-in-vivo-evaluations
#19
A M Abdel-Mohsen, J Jancar, R M Abdel-Rahman, L Vojtek, P Hyršl, M Dušková, H Nejezchlebová
In-situ formed hyaluronan/silver (HA/Ag) nanoparticles (NPs) were used to prepare composite fibers/fabrics for the first time. Different concentrations of silver nitrate (1, 2mg/100ml) were added at ambient temperature to sodium hyaluronate solution (40mg/ml), then the pH was increased to 8 by adding sodium hydroxide. The in-situ formed HA/Ag-NPs were used to prepare fibers/nonwoven fabrics by wet-dry-spinning technique (WDST). UV/vis spectroscopy, SEM, TEM, DLS, XPS, XRD and TGA were employed to characterize the structure and composition of the nanocomposite, surface morphology of fiber/fabrics, particle size of Ag-NPs, chemical interactions of Ag(0) and HA functional groups, crystallinity and thermal stability of the wound dressing, respectively...
February 3, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28161704/serum-derived-hyaluronan-associated-protein-is-a-novel-biomarker-for-inflammatory-bowel-diseases
#20
Yoshiharu Yamaguchi, Hisatsugu Noda, Noriko Okaniwa, Kazunori Adachi, Tetsuya Shinmura, Shoko Nakagawa, Masahide Ebi, Naotaka Ogasawara, Yasushi Funaki, Lisheng Zhuo, Koji Kimata, Makoto Sasaki, Kunio Kasugai
BACKGROUND/AIMS: We evaluated the role of serum-derived hyaluronan-associated protein (SHAP) in inflammatory bowel disease (IBD) pathogenesis and its potential as a novel IBD biomarker. METHODS: We studied the SHAP expression in a mouse model of colitis and in human intestinal samples of IBD and compared serum concentrations with normal controls. RESULTS: SHAP was expressed in the connective tissue derived from inflamed regions of the intestine...
February 4, 2017: Digestion
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