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https://www.readbyqxmd.com/read/29667660/a-new-functional-membrane-protein-microarray-based-on-tethered-phospholipid-bilayers
#1
Meriem Chadli, Ofelia Maniti, Christophe Marquette, Bruno Tillier, Sandra Cortès, Agnès Girard-Egrot
A new prototype of a membrane protein biochip is presented in this article. This biochip was created by the combination of novel technologies of peptide-tethered bilayer lipid membrane (pep-tBLM) formation and solid support micropatterning. Pep-tBLMs integrating a membrane protein were obtained in the form of microarrays on a gold chip. The formation of the microspots was visualized in real-time by surface plasmon resonance imaging (SPRi) and the functionality of a GPCR (CXCR4), reinserted locally into microwells, was assessed by ligand binding studies...
April 18, 2018: Analyst
https://www.readbyqxmd.com/read/29667232/the-pleiotropic-cardiovascular-effects-of-dipeptidyl-peptidase-4-inhibitors
#2
REVIEW
Angelo Avogaro, Gian Paolo Fadini
Patients with Type 2 Diabetes have an excess risk for cardiovascular disease. One of the several approaches, included in the Guidelines for the management of Type 2 Diabetes, is based on dipeptidyl peptidase 4 (DPP-4; also termed CD26) inhibitors (DPP-4-I), also called gliptins. Gliptins inhibit the degradation of glucagon-like peptide-1 GLP-1RA: this effect is associated with increased circulating insulin-to-glucagon ratio, and a consequent reduction of HbA1c. Beside incretin hormones, there are several proteins that may be affected by DPP-4 and its inhibition: among these some are relevant for the cardiovascular system homeostasis such as SDF-1α and its receptor CXCR4, brain natriuretic peptides, neuropeptide Y, and peptide YY...
April 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29666970/histopathological-and-molecular-predictors-of-growth-patterns-and-recurrence-in-craniopharyngiomas-a-systematic-review
#3
REVIEW
Josephine R Coury, Brittany N Davis, Christoforos P Koumas, Giovanna S Manzano, Amir R Dehdashti
Craniopharyngiomas (CPs) are rare, benign tumors derived from Rathke's pouch, known for their high recurrence rates and associated morbidity and mortality. Despite significant investigation on risk factors for recurrence, a lack of consensus persists. Recent research suggests that specific histopathological and molecular characteristics are prognostic for disease progression. In this systematic review, we analyzed and consolidated key features of CPs that contribute to increased recurrence rates. This systematic review was performed in accordance with PRISMA guidelines...
April 17, 2018: Neurosurgical Review
https://www.readbyqxmd.com/read/29665227/microenvironment-induced-pim-kinases-promote-cxcr4-triggered-mtor-pathway-required-for-chronic-lymphocytic-leukaemia-cell-migration
#4
Emilia Białopiotrowicz, Patryk Górniak, Monika Noyszewska-Kania, Bartosz Puła, Hanna Makuch-Łasica, Grażyna Nowak, Aleksandra Bluszcz, Maciej Szydłowski, Ewa Jabłonska, Karolina Piechna, Tomasz Sewastianik, Anna Polak, Ewa Lech-Marańda, Bożena K Budziszewska, Maja Wasylecka-Juszczyńska, Katarzyna Borg, Krzysztof Warzocha, Wojciech Czardybon, Michał Gałęzowski, Renata Windak, Krzysztof Brzózka, Przemysław Juszczyński
Lymph node microenvironment provides chronic lymphocytic leukaemia (CLL) cells with signals promoting their survival and granting resistance to chemotherapeutics. CLL cells overexpress PIM kinases, which regulate apoptosis, cell cycle and migration. We demonstrate that BCR crosslinking, CD40 stimulation, and coculture with stromal cells increases PIMs expression in CLL cells, indicating microenvironment-dependent PIMs regulation. PIM1 and PIM2 expression at diagnosis was higher in patients with advanced disease (Binet C vs...
April 17, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29664678/endothelial-and-smooth-muscle-cell-interaction-via-foxm1-signaling-mediates-vascular-remodeling-and-pulmonary-hypertension
#5
Zhiyu Dai, Maggie M Zhu, Yi Peng, Hua Jin, Narsa Machireddy, Zhijian Qian, Xianming Zhang, You-Yang Zhao
RATIONALE: Angioproliferative vasculopathy is a hallmark of pulmonary arterial hypertension (PAH). However, little is known how endothelial cell (EC) and smooth muscle cell (SMC) crosstalk regulates the angioproliferative vascular remodeling. OBJECTIVES: We aimed to investigate the role of EC and SMC interaction and underlying signaling pathways in PH development. METHODS: SMC-specific Foxm1 or Cxcr4 knockout mice, EC-specific Foxm1 or Egln1 knockout mice, as well as EC-specific Egln1/Cxcl12 double knockout mice were used to assess the role of FoxM1 on SMC proliferation and PH...
April 17, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29662864/expression-of-adhesion-molecules-on-cd34-cells-from-steady-state-bone-marrow-before-and-after-mobilization-and-their-association-with-the-yield-of-cd34-cells
#6
Karin Zattar Cecyn, Eliza Y S Kimura, Dulce Marta S M Lima, Miyoko Yamamoto, José Orlando Bordin, José Salvador R de Oliveira
Background: Cell adhesion molecules (CAMs) expressed on hematopoietic progenitor cells (HPCs), endothelial cells, and stromal cells play a pivotal role in the mobilization of CD34+ cells. Herein, we conducted a non-randomized peripheral blood stem cell (PBSC) mobilization study aimed to compare the potential differences in the expressions of several CAMs and chemokines on CD34+ cells obtained from bone marrow aspirate before and after HPC mobilization from patients with hematologic malignancies and healthy donors...
March 2018: Blood Research
https://www.readbyqxmd.com/read/29661775/prospective-clinical-trial-of-ixazomib-dexamethasone-and-rituximab-as-primary-therapy-in-waldenstr%C3%A3-m-macroglobulinemia
#7
Jorge J Castillo, Kirsten Meid, Joshua Gustine, Toni Dubeau, Patricia Severns, Zachary R Hunter, Guang Yang, Lian Xu, Steven P Treon
INTRODUCTION: Proteasome inhibition is of proven efficacy in patients with Waldenström macroglobulinemia (WM). However, WM remains incurable with standard treatments. Novel agents, safe and effective, are needed. METHODS: We designed a prospective phase II study evaluating the combination of ixazomib, dexamethasone and rituximab (IDR) as primary therapy in symptomatic patients with WM. Protocol therapy consisted of oral ixazomib, 4 mg, with intravenous or oral dexamethasone, 20 mg, on days 1, 8 and 15 every 4 weeks for induction cycles 1 and 2, and in combination with intravenous rituximab, 375 mg/m2, on day 1, every 4 weeks for cycles 3 to 6...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29661652/next-generation-sequencing-reveals-a-high-frequency-of-cxcr4-utilizing-viruses-in-hiv-1-chronically-infected-drug-experienced-individuals-in-south-africa
#8
Nontokozo D Matume, Denis M Tebit, Laurie R Gray, Marie-Louise Hammarskjold, David Rekosh, Pascal O Bessong
BACKGROUND: Entry inhibitors, such as Maraviroc, bind to CCR5 inhibiting entry of CCR5 utilizing viruses (R5 viruses). In the course of HIV infection, CXCR4 utilizing viruses (X4 viruses) may emerge and outgrow R5 viruses, and potentially limit the effectiveness of Maraviroc. The use of Maraviroc is reserved for salvage therapy in South Africa. OBJECTIVE: In this study, we examined the frequency of R5 and X4 viruses, using next generation sequencing, in patients under treatment to draw inferences on the utility of Maraviroc in a South African population...
February 15, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/29661298/engineering-of-thermoresponsive-gels-as-a-fake-metastatic-niche
#9
Simona Giarra, Caterina Ierano, Marco Biondi, Maria Napolitano, Virginia Campani, Roberto Pacelli, Stefania Scala, Giuseppe De Rosa, Laura Mayol
Chemoattraction through the CXCR4-CXCL12 axis has been shown to be an important mechanism to direct circulating tumor cells toward distant sites. The objective of this work was to prepare a fake metastatic niche made up of a gel loaded with CXCL12. The gel is designed to create a steep concentration gradient of the chemokine in the proximity of the site of administration/injection, aimed to divert and capture circulating CXCR4+ tumor cells. To this aim, different thermoresponsive gels based on methylcellulose (MC) or poloxamers, loaded with CXCL12, with or without hyaluronic acid (HA) were designed and their mechanical properties correlated with the ability to attract and capture in vitro CXCR4+ cells...
July 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29659363/-late-diagnosis-of-whim-sydrome
#10
María V Paolini, Silvia Danielian, Emma Prieto, María Fernanda Tami, Matías M Oleastro, Diego S Fernández Romero
WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4 mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathesis. Treatment consists in prophylactic antibiotics, immunoglobulin replacement and granulocyte or granulocyte/monocyte colony stimulating factors. We present the case of a 21 year old woman who showed leukopenia at 10 months of age and one year later multiple infections with hypogammaglobulinemia requiring intravenous immunoglobulin...
2018: Medicina
https://www.readbyqxmd.com/read/29658658/-icaritin-promotes-maturation-and-mineralization-of-mouse-osteoblast-mc3t3-e1-cells-through-cxcr4-sdf-1-signal-pathway
#11
Zhenlong Wei, Wengui Shi, Keming Chen, Jian Zhou, Minggang Wang
<b>Objective:</b> To investigate the effect of icaritin on maturation and mineralization of mouse osteoblast MC3T3-E1 cells and its mechanism. <b>Methods:</b> The cultured MC3T3-E1 cells were divided into blank control group, CXC chemokine receptor type 4 (CXCR4) inhibitor (AMD3100) group, icaritin group, and icaritin plus AMD3100 group. The expression of CXCR4, stromal cell-derived factor 1 (SDF-1) and osteogenesis-related genes and proteins were detected by real-time RT-PCR and Western blotting after drug treatment for 24 h...
May 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/29658570/jwa-suppresses-the-invasion-of-human-breast-carcinoma-cells-by-downregulating-the-expression-of-cxcr4
#12
Lingyun Xu, Lin Cheng, Fangliang Yang, Bei Pei, Xiaoan Liu, Jianwei Zhou, Yulan Zhu, Shui Wang
Breast cancer is the second leading cause of cancer‑associated mortality, and metastatic breast cancer is responsible for 90% of patient mortalities. Given that JWA represses the proliferation, invasion and metastasis of a number of other human tumor cells, including melanoma, esophageal, hepatocellular and gastric carcinomas, via mitogen‑activated protein kinase or integrin signaling, the present study investigated the expression and function of JWA in human breast cancers. The results showed that the expression level of JWA was significantly reduced in human primary breast cancers when compared with the paired adjacent tissues...
April 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29658309/individuals-with-hiv-1-subtype-c-infection-and-cryptococcal-meningitis-exhibit-viral-genetic-intermixing-of-hiv-1-between-plasma-and-cerebrospinal-fluid-and-a-high-prevalence-of-cxcr4-using-variants
#13
Katlego Sojane, Richard T Kangethe, Christina C Chang, Mahomed-Yunus Moosa, Sharon Ruth Lewin, Martyn A French, Thumbi Ndung'u
The genotypic properties of HIV-1 subtype C in individuals presenting with cryptococcal meningitis (CM) are not well established. Employing single-genome amplification as well as bulk PCR, cloning and sequencing strategies, we evaluated the genetic properties of HIV-1 subtype C env in 16 antiretroviral therapy naïve study participants with CM. Eleven of the 16 participants had matched blood plasma and cerebrospinal fluid (CSF) evaluated, with the rest having either a plasma or CSF sample evaluated. Before antiretroviral therapy initiation, matched plasma and cerebrospinal fluid-derived env sequences of all 11 participants displayed genetic intermixing between the two compartments...
April 15, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29649974/delayed-and-repeated-intranasal-delivery-of-bone-marrow-stromal-cells-increases-regeneration-and-functional-recovery-after-ischemic-stroke-in-mice
#14
Monica J Chau, Todd C Deveau, Xiaohuan Gu, Yo Sup Kim, Yun Xu, Shan Ping Yu, Ling Wei
BACKGROUND: Stroke is a leading cause of death and disability worldwide, yet there are limited treatments available. Intranasal administration is a novel non-invasive strategy to deliver cell therapy into the brain. Cells delivered via the intranasal route can migrate from the nasal mucosa to the ischemic infarct and show acute neuroprotection as well as functional benefits. However, there is little information about the regenerative effects of this transplantation method in the delayed phase of stroke...
April 12, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29649432/nitric-oxide-signaling-regulates-tumor-induced-intussusceptive-like-angiogenesis
#15
Selvaraj Vimalraj, Srinivasan Bhuvaneswari, Sundaresan Lakshmikirupa, Ganesh Jyothsna, Suvro Chatterjee
Existing animal models for screening tumor angiogenic process have various setbacks that necessitate further investigations. In this study, we developed an ex-ovo egg yolk angiogenesis model to screen the angiogenic potency of tumor cells (HeLa and SiHa cell lines). The egg yolk angiogenesis assay was applied to study the nitric oxide (NO) influence on switching from sprouting angiogenesis (SA) to intussusceptive angiogenesis (IA) under tumor microenvironment. Morphological analysis and SA-like or IA-like markers expression were determined during the development of chicken chorioallantoic membrane (CAM) from day 5 to 13...
April 9, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29644002/loss-of-neutrophil-polarization-in-colon-carcinoma-liver-metastases-of-mice-with-an-inducible-liver-specific-igf-i-deficiency
#16
Roni F Rayes, Simon Milette, Maria Celia Fernandez, Boram Ham, Ni Wang, France Bourdeau, Stephanie Perrino, Shoshana Yakar, Pnina Brodt
The growth of cancer metastases in the liver depends on a permissive interaction with the hepatic microenvironment and neutrophils can contribute to this interaction, either positively or negatively, depending on their phenotype. Here we investigated the role of IGF-I in the control of the tumor microenvironment in the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID) induced by a single tamoxifen injection. In mice that had a sustained (3 weeks) IGF-I deficiency prior to the intrasplenic/portal inoculation of colon carcinoma MC-38 cells, we observed an increase in neutrophil accumulation in the liver relative to controls...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29627496/simvastatin-inhibits-sonic-hedgehog-signaling-and-stemness-features-of-pancreatic-cancer
#17
Yefeng Yin, Li Liu, Zhefu Zhao, Libo Yin, Nathalie Bauer, Clifford C Nwaeburu, Jury Gladkich, Wolfgang Gross, Thilo Hackert, Carsten Sticht, Norbert Gretz, Oliver Strobel, Ingrid Herr
Pancreatic ductal adenocarcinoma (PDA) has poor therapeutic options. Recent patient studies indicate that cholesterol-lowering statins have anti-tumor capacities. We examined several established and primary PDA and normal cell lines as well as PDA patient tissues (n = 68). We found that simvastatin inhibited viability, stemness, tumor growth and metastasis and that it enhanced the efficacy of gemcitabine. These changes were associated with modulation of Shh-related gene expression. Overexpression of Shh prevented the anti-cancer effect of simvastatin, and inhibition of Shh mimicked the simvastatin effect...
April 5, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29627450/combined-thermodynamic-and-kinetic-analysis-of-groel-interacting-with-cxcr4-transmembrane-peptides
#18
Haixia Chi, Baomei Xu, Zhenzhen Liu, Junting Wei, Shixin Li, Hao Ren, Yan Xu, Xinwei Lu, Xiaojuan Wang, Xiaoqiang Wang, Fang Huang
GroEL along with ATP and its co-chaperonin GroES has been demonstrated to significantly enhance the folding of newly translated G-protein-coupled receptors (GPCRs). This work extends the previous studies to explore the guest capture and release processes in GroEL-assisted folding of GPCRs, by the reduced approach of employing CXCR4 transmembrane peptides as model substrates. Each of the CXCR4-derived peptides exhibited high affinity for GroEL with a binding stoichiometry near seven. It is found that the peptides interact with the paired α helices in the apical domain of the chaperonin which are similar with the binding sites of SBP (strongly binding peptide: SWMTTPWGFLHP)...
April 5, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29626713/differentiation-of-hepatocyte-like-cells-from-human-pluripotent-stem-cells-using-small-molecules
#19
Faizal Z Asumda, Konstantinos E Hatzistergos, Derek M Dykxhoorn, Silvia Jakubski, Jasmine Edwards, Emmanuel Thomas, Eugene R Schiff
A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific differentiation into definitive endoderm, hepatoblast and hepatocyte-like derivatives...
March 27, 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29625032/separating-actin-dependent-chemokine-receptor-nanoclustering-from-dimerization-indicates-a-role-for-clustering-in-cxcr4-signaling-and-function
#20
Laura Martínez-Muñoz, José Miguel Rodríguez-Frade, Rubén Barroso, Carlos Óscar S Sorzano, Juan A Torreño-Pina, César A Santiago, Carlo Manzo, Pilar Lucas, Eva M García-Cuesta, Enric Gutierrez, Laura Barrio, Javier Vargas, Graciela Cascio, Yolanda R Carrasco, Francisco Sánchez-Madrid, María F García-Parajo, Mario Mellado
A current challenge in cell motility studies is to understand the molecular and physical mechanisms that govern chemokine receptor nanoscale organization at the cell membrane, and their influence on cell response. Using single-particle tracking and super-resolution microscopy, we found that the chemokine receptor CXCR4 forms basal nanoclusters in resting T cells, whose extent, dynamics, and signaling strength are modulated by the orchestrated action of the actin cytoskeleton, the co-receptor CD4, and its ligand CXCL12...
April 5, 2018: Molecular Cell
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