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https://www.readbyqxmd.com/read/29778505/novel-peptide-nanoparticle-biased-antagonist-of-ccr3-blocks-eosinophil-recruitment-and-airway-hyperresponsiveness
#1
Milica Grozdanovic, Kimberly G Laffey, Hazem Abdelkarim, Ben Hitchinson, Anantha Harijith, Hyung-Geon Moon, Gye Young Park, Lee K Rousslang, Joanne C Masterson, Glenn T Furuta, Nadya I Tarasova, Vadim Gaponenko, Steven J Ackerman
BACKGROUND: Chemokine signaling through CCR3 is a key regulatory pathway for eosinophil recruitment into tissues associated with allergic inflammation and asthma. To date, none of the CCR3 antagonists have shown efficacy in clinical trials. One reason may be their unbiased mode of inhibition that prevents receptor internalization, leading to drug tolerance. OBJECTIVE: We sought to develop a novel peptide nanoparticle CCR3 inhibitor (R321) with a biased mode of inhibition that would block G-protein signaling, but enable or promote receptor internalization...
May 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29777988/insight-into-structural-requirements-for-selective-and-or-dual-cxcr3-and-cxcr4-allosteric-modulators
#2
Anja Kolarič, Urban Švajger, Tihomir Tomašič, Regine Brox, Theresa Frank, Nikola Minovski, Nuska Tschammer, Marko Anderluh
Based on the previously published pyrazolopyridine-based hit compound for which negative allosteric modulation of both CXCR3 and CXCR4 receptors was disclosed, we designed, synthesized and biologically evaluated a set of novel, not only negative, but also positive allosteric modulators with preserved pyrazolopyridine core. Compound 9e is a dual negative modulator, inhibiting G protein activity of both receptors. For CXCR4 receptor para-substituted aromatic group of compounds distinguishes between negative and positive modulation...
May 11, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29777657/mcv-mir-m1-targets-the-host-cell-immune-response-resulting-in-the-attenuation-of-neutrophil-chemotaxis
#3
P Akhbari, D Tobin, K Poterlowicz, W Roberts, J R Boyne
Virus-encoded miRNAs are emerging as key regulators of persistent infection and host-cell immune evasion. Merkel cell polyomavirus (MCPyV), the predominant aetiological agent of Merkel cell carcinoma (MCC), encodes a single miRNA, MCV-miR-M1, which targets the oncogenic MCPyV large T antigen (LT). MCV-miR-M1 has previously been shown to play an important role in establishment of long-term infection, however, the underlying mechanism is not fully understood. A key unanswered question is whether, in addition to auto-regulating LT, MCV-miR-M1 also targets cellular transcripts to orchestrate an environment conducive for persistent infection...
May 16, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29776055/optimal-methylation-noise-for-best-chemotactic-performance-of-e-coli
#4
Subrata Dev, Sakuntala Chatterjee
In response to a concentration gradient of chemoattractant, E. coli bacterium modulates the rotational bias of flagellar motors which control its run-and-tumble motion, to migrate towards regions of high chemoattractant concentration. Presence of stochastic noise in the biochemical pathway of the cell has important consequences on the switching mechanism of motor bias, which in turn affects the runs and tumbles of the cell in a significant way. We model the intracellular reaction network in terms of coupled time evolution of three stochastic variables-kinase activity, methylation level, and CheY-P protein level-and study the effect of methylation noise on the chemotactic performance of the cell...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29772391/development-of-ionic-liquid-assisted-synthesized-nano%C3%A2-silver-combined-with-vascular-endothelial-growth-factor-as-wound-healing-in-the-care-of-femoral-fracture-in-the-children-after-surgery
#5
Xingli Li, Maohua Liu, Hongxia Cheng, Qun Wang, Chuanna Miao, Shumei Ju, Fang Liu
This investigation aimed to develop the silver (Ag) nanoparticles incorporated vascular endothelial growth factor (VEGF) for the improvement wound healing and reduce Aseptic necrosis in treatment of femoral fracture healing. The spherical shaped Ag nanoparticles with improved morphology have been effectively synthesized via microwave assisted method using ionic liquids 1-dodecyl-3-methylimidazolium chloride. The morphological structure and crystalline properties of Ag nanoparticles are analyzed by using UV, XRD and TEM-EDX analytical methods...
March 6, 2018: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29771911/asymmetric-polar-localization-dynamics-of-the-serine-chemoreceptor-protein-tsr-in-escherichia-coli
#6
Dongmyung Oh, Yang Yu, Hochan Lee, Jae-Hyung Jeon, Barry L Wanner, Ken Ritchie
The spatial location of proteins in living cells can be critical for their function. For example, the E. coli chemotaxis machinery is localized to the cell poles. Here we describe the polar localization of the serine chemoreceptor Tsr using a strain synthesizing a fluorescent Tsr-Venus fusion at a low level from a single-copy chromosomal construct. Using photobleaching and imaging during recovery by new synthesis, we observed distinct asymmetry between a bright (old) pole and a dim (new) pole. The old pole was shown to be a more stable cluster and to recover after photobleaching faster, which is consistent with the hypothesis that newly synthesized Tsr proteins are inserted directly at or near the old pole...
2018: PloS One
https://www.readbyqxmd.com/read/29768676/ccl19-with-ccl21-tail-displays-enhanced-glycosaminoglycan-binding-with-retained-chemotactic-potency-in-dendritic-cells
#7
Astrid S Jørgensen, Pontian E Adogamhe, Julia M Laufer, Daniel F Legler, Christopher T Veldkamp, Mette M Rosenkilde, Gertrud M Hjortø
CCL19 is more potent than CCL21 in inducing chemotaxis of human dendritic cells (DC). This difference is attributed to 1) a stronger interaction of the basic C-terminal tail of CCL21 with acidic glycosaminoglycans (GAGs) in the environment and 2) an autoinhibitory function of this C-terminal tail. Moreover, different receptor docking modes and tissue expression patterns of CCL19 and CCL21 contribute to fine-tuned control of CCR7 signaling. Here, we investigate the effect of the tail of CCL21 on chemokine binding to GAGs and on CCR7 activation...
May 16, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29768163/tissue-damage-signaling-is-a-prerequisite-for-protective-neutrophil-recruitment-to-microbial-infection-in-zebrafish
#8
Cong Huang, Philipp Niethammer
Tissue damage and infection are deemed likewise triggers of innate immune responses. But whereas neutrophil responses to microbes are generally protective, neutrophil recruitment into damaged tissues without infection is deleterious. Why neutrophils respond to tissue damage and not just to microbes is unknown. Is it a flaw of the innate immune system that persists because evolution did not select against it, or does it provide a selective advantage? Here we dissect the contribution of tissue damage signaling to antimicrobial immune responses in a live vertebrate...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29766831/phagocytosis-and-motility-in-human-neutrophils-is-competent-but-compromised-by-pharmacological-inhibition-of-ezrin-phosphorylation
#9
Rhiannon E Roberts, Geetha L Elumalai, Maurice B Hallett
BACKGROUND AND OBJECTIVE: Ezrin links the cortical cytoskeleton to the plasma membrane and plays a role in regulating cell shape change. Recently NSC668394 has been shown to inhibit a key step for its activity, i.e. phosphorylation at threonine 567. In neutrophils, another key regulatory step is the Ca2+-mediated cleavage of ezrin by calpain. METHODS: In this paper we use NSC668394 as a pharmacological inhibitor to investigate the interplay between these two steps in regulating neutrophil shape change...
May 15, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29764856/-tp53-stk11-and-egfr-mutations-predict-tumor-immune-profile-and-the-response-to-anti-pd-1-in-lung-adenocarcinoma
#10
Jerome Biton, Audrey Mansuet-Lupo, Nicolas Pécuchet, Marco Alifano, Hanane Ouakrim, Jennifer Arrondeau, Pascaline Boudou-Rouquette, Francois Goldwasser, Karen Leroy, Jeremy Goc, Marie Wislez, Claire Germain, Pierre Laurent-Puig, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Ronald Herbst, Hélène F Blons, Diane Damotte
PURPOSE: By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. EXPERIMENTAL DESIGN: We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29763693/influence-of-lipopolysaccharide-on-proinflammatory-gene-expression-in-human-corneal-conjunctival-and-meibomian-gland-epithelial-cells
#11
Di Chen, Afsun Sahin, Wendy R Kam, Yang Liu, Raheleh Rahimi Darabad, David A Sullivan
PURPOSE: Lipopolysaccharide (LPS), a bacterial endotoxin, is known to stimulate leuokotriene B4 (LTB4) secretion by human corneal (HCECs), conjunctival (HConjECs) and meibomian gland (HMGECs) epithelial cells. We hypothesize that this LTB4 effect represents an overall induction of proinflammatory gene expression in these cells. Our objective was to test this hypothesis. METHODS: Immortalized HCECs, HConjECs and HMGECs were cultured in the presence or absence of LPS (15 μg/ml) and ligand binding protein (LBP; 150 ng/ml)...
May 12, 2018: Ocular Surface
https://www.readbyqxmd.com/read/29763691/insights-on-the-age-dependent-neurodegeneration-induced-by-monocrotophos-an-organophosphorous-insecticide-in-caenorhabditis-elegans-fed-high-glucose-evidence-in-wild-and-transgenic-strains
#12
Chinnu Salim, Nidheesh Thadathil, M Muralidhara, P S Rajini
The higher susceptibility of high glucose fed C. elegans to Monocrotophos (MCP, an organophosphorus insecticide) - induced dopaminergic (DA) neuronal degeneration was recently demonstrated. Employing this acute exposure model, the impact of MCP on DA degeneration among worms of two age groups (8 and 13 d old) fed control (CO) and high glucose (GF) diet with specific focus on phenotypic alterations, oxidative impairments and associated molecular perturbations employing both wild (N2) and transgenic strains(BZ555 and NL5901) was investigated...
May 12, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29761401/in-vitro-migration-assays
#13
Lewis Taylor, Carlota Recio, David R Greaves, Asif J Iqbal
The timely recruitment of innate and adaptive immune cells to sites of inflammation and repair is essential for host defense against pathogens and repair of damaged tissues. The development of bioassays such as in vitro chemotaxis assays played an important role in the original purification of chemoattractant cytokines including interleukin-1 and the CC and CXC chemokines. The earliest chemotaxis methods were based on the principle of the Boyden chamber, first described in 1962. In this chapter we give detailed protocols for more recent techniques that allow determination of macrophage chemotaxis in real time...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29758623/pseudochemotaxis-in-inhomogeneous-active-brownian-systems
#14
Hidde D Vuijk, Abhinav Sharma, Debasish Mondal, Jens-Uwe Sommer, Holger Merlitz
We study dynamical properties of confined, self-propelled Brownian particles in an inhomogeneous activity profile. Using Brownian dynamics simulations, we calculate the probability to reach a fixed target and the mean first passage time to the target of an active particle. We show that both these quantities are strongly influenced by the inhomogeneous activity. When the activity is distributed such that high-activity zone is located between the target and the starting location, the target finding probability is increased and the passage time is decreased in comparison to a uniformly active system...
April 2018: Physical Review. E
https://www.readbyqxmd.com/read/29758486/poly-i-c-and-lps-induce-distinct-immune-responses-by-ovarian-stromal-fibroblasts
#15
Mickey V Patel, Zheng Shen, Charles R Wira
Despite its anatomical location, the ovary is a site of pathogen exposure in the human female reproductive tract (FRT). However, the role of ovarian stromal fibroblasts in immune protection is unclear. We generated a population of ovarian stromal fibroblasts derived from normal human ovaries that expressed the pattern recognition receptors TLR3, TLR4, RIG-I, & MDA5. Poly (I:C) and LPS, respective mimics of viral and bacterial infections, selectively upregulated antiviral gene expression and secretion of chemokines and antimicrobials...
May 9, 2018: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29757152/dynamic-seesaw-model-for-rapid-signaling-responses-in-eukaryotic-chemotaxis
#16
Shiliang Feng, Lvwen Zhou, ShouQin Lü, Yan Zhang
Directed movement of eukaryotic cells toward spatiotemporally varied chemotactic stimuli enables rapid intracellular signaling responses. While macroscopic cellular manifestation is shaped by balancing external stimuli strength with finite internal delays, the organizing principles of the underlying molecular mechanisms remain to be clarified. Here, we developed a novel modeling framework based on a simple seesaw mechanism to elucidate how cells repeatedly reverse polarity. As a key feature of the modeling, the bottom module of bidirectional molecular transport is successively controlled by three upstream modules of signal reception, initial signal processing, and Rho GTPase regulation...
May 14, 2018: Physical Biology
https://www.readbyqxmd.com/read/29756050/effects-of-arginine-vasopressin-on-migration-and-respiratory-burst-activity-in-human-leukocytes
#17
Franz J Wiedermann, Kathrin Watzinger, Martina Stichlberger, Michael Joannidis, Christian Kaehler, Wolfgang Lederer
Arginine vasopressin can bind to high-affinity vasopressin V1a receptors in human leukocytes. This study aims to investigate the effects of arginine vasopressin on migration and chemotaxis of neutrophils and oxygen free radical release by human leukocytes. Neutrophils and monocytes were obtained from peripheral blood samples of ten healthy volunteers. Leukocyte migration was microscopically assessed in a modified 48-blind well microchemotaxis chamber, and respiratory burst activity was estimated using 2',7'-dichlorofluorescin diacetate in descending concentrations of arginine vasopressin...
2018: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/29755672/inhibition-of-mtor-complex-2-restrains-tumor-angiogenesis-in-multiple-myeloma
#18
Aurelia Lamanuzzi, Ilaria Saltarella, Vanessa Desantis, Maria Antonia Frassanito, Patrizia Leone, Vito Racanelli, Beatrice Nico, Domenico Ribatti, Paolo Ditonno, Marcella Prete, Antonio Giovanni Solimando, Francesco Dammacco, Angelo Vacca, Roberto Ria
The mammalian Target of Rapamycin (mTOR) is an intracellular serine/threonine kinase that mediates intracellular metabolism, cell survival and actin rearrangement. mTOR is made of two independent complexes, mTORC1 and mTORC2, activated by the scaffold proteins RAPTOR and RICTOR, respectively. The activation of mTORC1 triggers protein synthesis and autophagy inhibition, while mTORC2 activation promotes progression, survival, actin reorganization, and drug resistance through AKT hyper-phosphorylation on Ser473...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752469/microrna-17-92-cluster-promotes-the-proliferation-and-the-chemokine-production-of-keratinocytes-implication-for-the-pathogenesis-of-psoriasis
#19
Weigang Zhang, Xiuli Yi, Yawen An, Sen Guo, Shuli Li, Pu Song, Yuqian Chang, Shaolong Zhang, Tianwen Gao, Gang Wang, Chunying Li
Keratinocytes are the main epidermal cell type that constitutes the skin barrier against environmental damages, which emphasizes the balance between the growth and the death of keratinocytes in maintaining skin homeostasis. Aberrant proliferation of keratinocytes and the secretion of inflammatory factors from keratinocytes are related to the formation of chronic inflammatory skin diseases like psoriasis. MicroRNA-17-92 (miRNA-17-92 or miR-17-92) is a miRNA cluster that regulates cell growth and immunity, but the role of miR-17-92 cluster in keratinocytes and its relation to skin diseases have not been well investigated...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29752100/squid-type-ii-collagen-as-a-novel-biomaterial-isolation-characterization-immunogenicity-and-relieving-effect-on-degenerative-osteoarthritis-via-inhibiting-stat1-signaling-in-pro-inflammatory-macrophages
#20
Meilu Dai, Xin Liu, Nanping Wang, Jiao Sun
Collagen from marine organisms has a broad prospect in biomedical field, yet the knowledge on marine-derived type II collagen is rare. Herein, a novel type II collagen was successfully isolated from squid cartilage for the first time. After being characterized, the immunogenicity of squid type II collagen (SCII) was evaluated and compared with that of bovine type II collagen (BCII). Then investigations were further conducted for the impacts of SCII on pro-inflammatory macrophages and macrophage chemotaxis. The degenerative osteoarthritis (OA) -relieving effects of SCII were explored using OA rat model in vivo...
August 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
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