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https://www.readbyqxmd.com/read/28821152/the-common-lavender-lavandula-angustifolia-mill-pectic-polysaccharides-modulate-phagocytic-leukocytes-and-intestinal-peyer-s-patch-cells
#1
Yordan N Georgiev, Berit S Paulsen, Hiroaki Kiyohara, Milan Ciz, Manol H Ognyanov, Ondrej Vasicek, Frode Rise, Petko N Denev, Haruki Yamada, Antonin Lojek, Vesselin Kussovski, Hilde Barsett, Albert I Krastanov, Irina Z Yanakieva, Maria G Kratchanova
Two pectic (chPS-L1, chPS-L2) and one polyphenolic (chPP-L) fractions were obtained from lavender flowers after boiling water extraction, exhaustive removing of alcohol-soluble molecules and SEC. chPS-L1 (52.4kDa) contains mainly low-acetylated and high-methoxylated homogalacturonans (HG), and smaller rhamnogalacturonan (RG) I backbone fragments rich in 1,3,5-branched arabinan and arabinogalactan (AG) II side chains. chPS-L2 (21.8kDa) contains predominantly similarly esterified HG, followed by RGI with AGII structures and RGII...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28821028/targeted-gene-delivery-of-polyethyleneimine-grafted-chitosan-with-rgd-dendrimer-peptide-in-%C3%AE-v%C3%AE-3-integrin-overexpressing-tumor-cells
#2
Young-Min Kim, Seong-Cheol Park, Mi-Kyeong Jang
The safe and effective delivery of genetic material into cells is a necessary factor for gene therapy. Although a wide range of materials, methods, and combinations have been reported, successful gene therapy has been limited. In the present study, a targeted gene carrier for αvβ3 integrin-overexpressing tumor cells was designed using widely applied materials containing water soluble chitosan (WSC), RGD peptide, and polyethyleneimine (PEI). The physiological characteristics, in vitro targeted gene transfection, cytotoxicity, blood-compatibility, and cellular distributions were investigated...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28820575/mbg-modified-%C3%AE-tcp-scaffold-promotes-mesenchymal-stem-cells-adhesion-and-osteogenic-differentiation-via-fak-mapk-signaling-pathway
#3
Yutong Liu, Yifan Ma, Jing Zhang, Qing Xie, Zi Wang, Shuang Yu, Yuan Yuan, Changsheng Liu
β-TCP scaffold has been widely used as bone graft substitutes, but traditional PMMA molding method-induced undesirable mechanical strength and poor interconnectivity still have not addressed till now. In this study, a MBG-based PU foam templating method was developed to fabricate β-TCP scaffolds with desirable microtopography. The MBG gel, as both binder and modifier, prepared by modified sol-gel method with controlled viscosity is incorporated with β-TCP powder and thereafter is impregnated into PU foam...
August 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28820394/the-c-terminal-region-of-the-focal-adhesion-kinase-f1-domain-binds-akt1-and-inhibits-pressure-induced-cell-adhesion
#4
M D Basson, B Zeng, S Wang
Increased extracellular pressure or shear stress activate a complex signal pathway that stimulates integrin binding affinity and potentiates metastatic cell adhesion. Inhibiting either focal adhesion kinase (FAK) and Akt1 can block this pathway, but risks interfering with the diverse other functions of each kinase. However, the mechanotransduced signal pathway involves a novel Akt1-FAK interaction not required for most FAK or Akt1 function, so modeling and blocking this interaction seems a desirable target...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819999/high-glucose-induces-hgf-independent-activation-of-met-receptor-in-human-renal-tubular-epithelium
#5
Lucia Mesarosova, Peter Ochodnicky, Jaklien C Leemans, Sandrine Florquin, Peter Krenek, Jan Klimas
CONTEXT: The role of hepatocyte growth factor (HGF) in diabetic kidney damage remains controversial. OBJECTIVE: To test the hypothesis that high glucose levels activate pathways related to HGF and its receptor Met and that this could participate in glucose-induced renal cell damage. MATERIALS AND METHODS: HK2 cells, a human proximal tubule epithelial cell line, were stimulated with high glucose for 48 hours. Levels of pMet/Met, pEGFR/EGFR, pSTAT3/STAT3, pAkt/Akt and pERK1/2/ERK1/2 were studied by immunoblotting...
August 18, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28819560/a-novel-peptide-blocking-cancer-cell-invasion-by-structure-based-drug-design
#6
Yuki Yamada, Seiji Kanayama, Fuminori Ito, Noriyuki Kurita, Hiroshi Kobayashi
The receptor for the urokinase-type plasminogen activator (uPA), uPAR, facilitates tumor cell invasion and metastasis by focusing on several ligands, including uPA, integrins and vitronectin. With computational prediction algorithms and structure-based drug design, we identified peptides containing the Gly-Lys-Gly-Glu-Gly-Glu-Gly-Lys-Gly sequence (peptide H1), which strongly interacts with uPAR. The aim of the present study was to investigate the effect of allosteric inhibition at the uPAR interface using a novel synthetic peptide and its function on ovarian cancer cell invasion...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28819447/targeting-activated-platelets-a-unique-and-potentially-universal-approach-for-cancer-imaging
#7
May Lin Yap, James D McFadyen, Xiaowei Wang, Nicholas A Zia, Jan David Hohmann, Melanie Ziegler, Yu Yao, Alan Pham, Matthew Harris, Paul S Donnelly, P Mark Hogarth, Geoffrey A Pietersz, Bock Lim, Karlheinz Peter
Rationale The early detection of primary tumours and metastatic disease is vital for successful therapy and is contingent upon highly specific molecular markers and sensitive, non-invasive imaging techniques. We hypothesized that the accumulation of activated platelets within tumours is a general phenomenon and thus represents a novel means for the molecular imaging of cancer. Here we investigate a unique single chain antibody (scFv), which specifically targets activated platelets, as a novel biotechnological tool for molecular imaging of cancer...
2017: Theranostics
https://www.readbyqxmd.com/read/28819423/reelin-promotes-adhesion-of-multiple-myeloma-cells-to-bone-marrow-stromal-cells-via-integrin-%C3%AE-1-signaling
#8
Liang Lin, Xinwei Zhang, Li Cao, Quanming An, Jie Hao, Yan Zhang, Rong Jin, Yingjun Chang, Xiaojun Huang, Jin Lu, Qing Ge
The close interaction between tumor cells and bone marrow stromal cells plays a crucial role in the tumorigenesis of multiple myeloma (MM). Reelin, an extracellular matrix protein, is found expressed in myeloma cells and is negatively associated with prognosis. We examined the role of Reelin in myeloma cell adhesion to bone marrow stromal cells and the signaling pathways involved. The results revealed that Reelin promoted the adhesion of myeloma cells to HS-5, a bone marrow stromal cell line, via the activation of β1 integrin...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818987/response-assessment-of-68-ga-dota-e-c-rgdfk-2-pet-ct-for-lung-adenocarcinoma-patients-treated-with-nintedanib-plus-docetaxel
#9
Oscar Arrieta, Francisco O Garcia-Perez, David Michel-Tello, Laura-Alejandra Ramirez-Tirado, Quetzali Pitalua-Cortes, Graciela Cruz-Rico, Eleazar-Omar Macedo-Perez, Andres F Cardona, Jaime de la Garza-Salazar
Nintedanib is an oral angiokinase inhibitor used as a second-line treatment for non-small-cell lung cancer (NSCLC). New radiotracers, such as (68)Ga-DOTA-E-[c(RGDfK)]2, that target αvβ3 integrin might impact the clinical practice as a non-invasive method for assessing angiogenesis inhibitors. Methods: From July 2014 through October 2015, 38 patients received second-line nintedanib plus docetaxel. All the patients underwent PET/CT with (68)Ga-DOTA-E-[c(RGDfK)]2 radiotracer and blood-sample tests to quantify angiogenesis factors (FGF, VEGF and PDGF-AB) prior to and after completing 2 therapy cycles...
August 17, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28818870/fra-2-negatively-regulates-postnatal-alveolar-septation-by-modulating-myofibroblast-function
#10
Kazuyuki Tsujino, John T Li, Tatsuya Tsukui, Xin Ren, Latifa Bakiri, Erwin F Wagner, Dean Sheppard
Mice that globally over-express the transcription factor, Fos-related antigen-2 (Fra-2), develop extensive pulmonary fibrosis and pulmonary vascular remodeling. To determine if these phenotypes are a consequence of ectopic Fra-2 expression in vascular smooth muscle cells and myofibroblasts, we generated mice that over-express Fra-2 specifically in these cells types (α-SMA-rtTA; tetO-Fra-2). Surprisingly, these mice did not develop vascular remodeling or pulmonary fibrosis, but developed a spontaneous emphysema-like phenotype characterized by alveolar enlargement...
August 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28817691/rac2-is-required-for-alternative-macrophage-activation-and-bleomycin-induced-pulmonary-fibrosis-a-macrophage-autonomous-phenotype
#11
Shweta Joshi, Alok R Singh, Simon S Wong, Muamera Zulcic, Min Jiang, Annie Pardo, Moises Selman, James S Hagood, Donald L Durden
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by cellular phenotype alterations and deposition of extracellular matrix proteins. The alternative activation of macrophages in the lungs has been associated as a major factor promoting pulmonary fibrosis, however the mechanisms underlying this phenomenon are poorly understood. In the present study, we have defined a molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin lead to the activation of Rac2 which regulates alternative macrophage differentiation, a signaling axis within the pulmonary macrophage compartment required for bleomycin induced pulmonary fibrosis...
2017: PloS One
https://www.readbyqxmd.com/read/28816404/multivalency-increases-the-binding-strength-of-rgd-peptidomimetic-paclitaxel-conjugates-to-integrin-%C3%AE-v%C3%AE-3
#12
Cesare Gennari, André Raposo Moreira Dias, Arianna Pina, Alberto Dal Corso, Daniela Arosio, Laura Belvisi, Luca Pignataro, Michele Caruso
Herein we report the synthesis of three multimeric RGD peptidomimetic-paclitaxel conjugates featuring a number of αVβ3 integrin ligands ranging from 2 to 4 (compounds 7-9). These constructs were assembled by conjugation of the integrin αVβ3 ligand cyclo[DKP-RGD]-CH2NH2 (2) with paclitaxel (3) via a 2'-carbamate with a self-immolative spacer, the lysosomally cleavable Val-Ala dipeptide linker, a multimeric scaffold, a triazole linkage, and finally a PEG spacer. Two monomeric conjugates (compounds 5-6) were also synthesized as reference compounds...
August 17, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28815933/an-%C3%AE-iib-%C3%AE-3-antagonist-prevents-thrombosis-without-causing-fc%C3%AE-riia-mediated-thrombocytopenia
#13
Yu-Ju Kuo, Ying-Ru Chen, Chun-Chieh Hsu, Hui-Chin Peng, Tur-Fu Huang
BACKGROUND: Thrombocytopenia, a common side effect of Arg-Gly-Asp (RGD)-mimetic antiplatelet drugs, is associated with drug-dependent antibodies (DDAbs) that recognize conformation-altered integrin αIIb β3 . OBJECTIVE: To explore the correlation between αIIb β3 binding epitopes and induction of DDAb binding to conformation-altered αIIb β3 , we examined whether two purified disintegrins TMV-2 and TMV-7 with distinct binding motifs that have different effects on induction of αIIb β3 conformational change and platelet aggregation in the presence of AP2, an IgG1 inhibitory monoclonal antibody (mAb) raised against αIIb β3 ...
August 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28815778/mapk8-regulates-chicken-male-germ-cell-differentiation-through-jnk-signaling-pathway
#14
Yingjie Wang, Yulin Bi, Qisheng Zuo, Wenhui Zhang, Dong Li, Na-Na He, Shaoze Cheng, Ya-Ni Zhang, Bichun Li
The study aims to analyze the key signaling pathways in regulating the process of embryonic stem cells (ESCs) differentiation into spermatogonial stem cells (SSCs). We explored the specific regulating mechanisms of C-Jun amino-terminal kinase (JNK) signaling in this process. Interference/overexpression of MAPK8 allows the JNK signaling pathway to be blocked/activated. In Retinoic acid (RA) induced in vitro differentiation assays, the expression of germ cell marker genes, cvh, c-kit, integrin α6 and integrin β1, was observed to upregulate while activating JNK signaling significantly...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#15
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28814519/extracellular-matrix-proteins-mediate-hiv-1-gp120-interactions-with-%C3%AE-4%C3%AE-7
#16
David Plotnik, Wenjin Guo, Brad Cleveland, Priska von Haller, Jimmy K Eng, Miklos Guttman, Kelly K Lee, James Arthos, Shiu-Lok Hu
Gut-homing α4β7(high) CD4(+) T lymphocytes have been shown to be preferentially targeted by Human Immunodeficiency Virus-1 (HIV), and are implicated in HIV pathogenesis. Previous studies demonstrated that HIV envelope protein gp120 binds and signals through α4β7, and that this likely contributes to the infection of α4β7(high) T cells and promotes cell-to-cell virus transmission. Structures within the second variable loop (V2) of gp120, including the tripeptide motif LDV/I, are thought to mediate gp120-α4β7 binding...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28813592/3d-printed-phema-materials-for-topographical-and-biochemical-modulation-of-dorsal-root-ganglion-cell-response
#17
Adina Badea, Joselle M McCracken, Emily G Tillmaand, Mikhail Eugene Kandel, Aaron W Oraham, Molly B Mevis, Stanislav S Rubakhin, Gabriel Popescu, Jonathan V Sweedler, Ralph G Nuzzo
Understanding and controlling the interactions occurring between cells and engineered materials are central challenges towards progress in the development of biomedical devices. In this work, we describe materials for direct ink writing (DIW), an extrusion-based type of 3D printing, that embed a custom synthetic protein (RGD-PDL) within the microfilaments of 3D-hydrogel scaffolds to modify these interactions and differentially direct tissue-level organization of complex cell populations in vitro. The RGD-PDL is synthesized by modifying poly-ᴅ-lysine (PDL) to varying extents with peptides containing the integrin-binding motif Arg-Gly-Asp (RGD)...
August 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28811641/joint-inflammation-related-citrullination-of-functional-arginines-in-extracellular-proteins
#18
Kalle H Sipilä, Vipin Ranga, Pekka Rappu, Markku Mali, Laura Pirilä, Ilona Heino, Johanna Jokinen, Jarmo Käpylä, Mark S Johnson, Jyrki Heino
We report the extent, specific sites and structural requirements of joint inflammation related citrullination in extracellular proteins. A total of 40 synovial fluid samples derived from chronically inflamed human joints were analysed by heparin-agarose fractionation and LC-MS/MS. Citrullination of 55 arginines in extracellular proteins was detected. Importantly, 20% of the sites have a characterized function related to the hallmarks of destructive joint inflammation. E.g. four arginine residues, shown here to be citrullinated, are also affected by mutations in inherited diseases causing haemolysis or blood clotting dysfunction...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811304/selectin-catch-bonds-mechanotransduce-integrin-activation-and-neutrophil-arrest-on-inflamed-endothelium-under-shear-flow
#19
Vasilios A Morikis, Shannon Chase, Ted Wun, Elliot L Chaikof, John L Magnani, Scott I Simon
E-selectin extends from the plasma membrane of inflamed endothelium and serves to capture leukocytes from flowing blood via long-lived catch-bonds that support slow leukocyte rolling under shear stress. Its ligands are glycosylated with the tetrasaccharide sialyl Lewis(x) (sLe(x)), which contributes to bond affinity and specificity. E-selectin mediated rolling transmits signals into neutrophils that triggers activation of high-affinity β2-integrins necessary for transition to shear resistant adhesion and transendothelial migration...
August 15, 2017: Blood
https://www.readbyqxmd.com/read/28809082/development-of-a-dual-functional-hydrogel-using-rgd-and-anti-vegf-aptamer
#20
Nan Zhao, Mark R Battig, Ming Xu, Xiuli Wang, Na Xiong, Yong Wang
Synthetic molecular libraries hold great potential to advance the biomaterial development. However, little effort is made to integrate molecules with molecular recognition abilities selected from different libraries into a single biomolecular material. The purpose of this work is to incorporate peptides and nucleic acid aptamers into a porous hydrogel to develop a dual-functional biomaterial. The data show that an anti-integrin peptide can promote the attachment and growth of endothelial cells in a 3D porous poly(ethylene glycol) hydrogel and an antivascular endothelial growth factor aptamer can sequester and release VEGF of high bioactivity...
August 15, 2017: Macromolecular Bioscience
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