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https://www.readbyqxmd.com/read/29334428/development-of-potent-inhibitors-of-the-mycobacterium-tuberculosis-virulence-factor-zmp1-and-evaluation-of-their-effect-on-mycobacterial-survival-inside-macrophages
#1
Marco Paolino, Margherita Brindisi, Alessandra Vallone, Stefania Butini, Giusepp Campiani, Chiara Nannicini, Germano Giuliani, Maurizio Anzini, Stefania Lamponi, Gianluca Giorgi, Diego Sbardella, Davide M Ferraris, Stefano Marini, Massimo Coletta, Ivana Palucci, Mariachiara Minerva, Giovanni Delogu, Ilaria Pepponi, Delia Goletti, Andrea Cappelli, Sandra Gemma, Simone Brogi
The enzyme Zmp1 is a zinc-peptidase having a critical role in M. tuberculosis pathogenicity. Here we describe the identification of a small set of Zmp1 inhibitors based on a novel 8-hydroxyquinoline-2-hydroxamate scaffold. Among the synthesized compounds, 1c was the most potent Zmp1 inhibitor known to date, and its binding mode was analysed both through kinetic studies and molecular modelling, identifying critical interactions of 1c with the zinc-ion and residues in the active site. Effect of 1c on intracellular Mycobacterium survival was assayed in J774 murine macrophages infected with M...
January 15, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29334374/transitory-presence-of-myeloid-derived-suppressor-cells-in-neonates-is-critical-for-control-of-inflammation
#2
Yu-Mei He, Xing Li, Michela Perego, Yulia Nefedova, Andrew V Kossenkov, Erik A Jensen, Valerian Kagan, Yu-Feng Liu, Shu-Yu Fu, Qing-Jian Ye, Yan-Hong Zhou, Lai Wei, Dmitry I Gabrilovich, Jie Zhou
Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions. Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics. No or very few MDSCs are observed in steady-state physiological conditions. Therefore, until recently, accumulation of MDSCs was considered a consequence of pathological processes or pregnancy...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334370/scaffolds-that-mimic-antigen-presenting-cells-enable-ex-vivo-expansion-of-primary-t-cells
#3
Alexander S Cheung, David K Y Zhang, Sandeep T Koshy, David J Mooney
Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-cell receptor stimulation and costimulation, while the micro-rods enable sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and interleukin-2, we show that the APC-mimetic scaffolds (APC-ms) promote two- to tenfold greater polyclonal expansion of primary mouse and human T cells compared with commercial expansion beads (Dynabeads)...
January 15, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29333081/innate-immunity-recovers-earlier-than-acquired-immunity-during-severe-postoperative-immunosuppression
#4
Gunnar Lachmann, Clarissa von Haefen, Johannes Kurth, Fatima Yuerek, Claudia Spies
Background: Postoperative immune suppression, particularly a loss of cell-mediated immunity, is commonly seen after surgery and is associated with worse outcome, i.e. delayed wound healing, infections, sepsis, multiple-organ failure and cancer recurrence. However, the recovery of immune cells focusing on differences between innate and acquired immunity during severe postoperative immunosuppression is not investigated. Methods: In this retrospective randomized controlled trial (RCT) subgroup analysis, 10 postoperatively immune suppressed patients after esophageal or pancreatic resection were analyzed...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29332916/mir-135a-promotes-inflammatory-responses-of-vascular-smooth-muscle-cells-from-db-db-mice-via-downregulation-of-foxo1
#5
Xiaochun Lu, Dawei Yin, Bo Zhou, Tieling Li
It has been shown that microRNAs (miRNAs) greatly affect the functions of vascular smooth muscle cells (VSMC), but the effects of mRNAs under diabetic conditions remain unclear.Using a model of diabetic db/db mice, we studied the functions of microRNA-135a (miR-135a) during VSMC dysfunction.Compared to control WT mice, miR-135a expression in VSMC was significantly increased while the level of forkhead box O1 (FOXO1) protein decreased significantly. After transfecting miR-135a mimics into VSMC, the expression of FOXO1 was decreased, while cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1) expression levels were increased, thus promoting the interaction between monocytes and WT VSMC...
January 15, 2018: International Heart Journal
https://www.readbyqxmd.com/read/29332562/the-delicate-balance-between-the-good-and-the-bad-il-1-proinflammatory-effects-in-endometriosis
#6
Justyna Sikora, Simone Ferrero, Aleksandra Mielczarek-Palacz, Zdzislawa Kondera-Anasz
BACKGROUND: Endometriosis is an inflammatory gynaecological disease with an associated chronic inflammation. Interleukin(IL)-1 is one of the most important immune and proinflammatory factors, produced mainly by monocytes and macrophages. Studies indicate the role of the cytokine from IL-1 family in endometrium-related disorders, particularly in endometriosis. METHODS: The information about the impact of cytokine from IL-1 cytokine family on the pathogenesis and development of endometriosis was obtained with an electronic literature search based on the PubMed and Medline databases, spanning the period of January 1950 to July 2017 and includes associated references in the published studies...
January 10, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29332538/role-of-infiltrating-monocytes-in-the-development-of-radiation-induced-pulmonary-fibrosis
#7
Angela M Groves, Carl J Johnston, Jacqueline P Williams, Jacob N Finkelstein
Lung exposure to radiation induces an injury response that includes the release of cytokines and chemotactic mediators; these signals recruit immune cells to execute inflammatory and wound-healing processes. However, radiation alters the pulmonary microenvironment, dysregulating the immune responses and preventing a return to homeostasis. Importantly, dysregulation is observed as a chronic inflammation, which can progress into pneumonitis and promote pulmonary fibrosis; inflammatory monocytes, which are bone marrow derived and express CCR2, have been shown to migrate into the lung after radiation exposure...
January 13, 2018: Radiation Research
https://www.readbyqxmd.com/read/29332250/the-levels-of-12-cytokines-and-growth-factors-in-tears-hyperthyreosis-vs-euthyreosis
#8
Jelena Juri Mandić, Ana Kozmar, Sanja Kusačić-Kuna, Anamarija Jazbec, Krešimir Mandić, Danijela Mrazovac, Nenad Vukojević
PURPOSE: Simultaneous analyses of the contents and ratios of 12 cytokines and growth factors in single samples of human tears were performed, and the results were compared between a group of healthy subjects and a group of patients with Graves' hyperthyreosis (GH) without thyroid-associated orbitopathy (TAO). METHODS: Determinations and concentration measurements of interleukins (IL-2, IL4, IL-6, IL-8, IL-10, IL-1α, and IL-1β) interferon (IFN-γ), tumor necrosis factor (TNF-α), monocyte chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were performed with single tear samples from 21 patients with hyperthyreosis and 22 healthy subjects...
January 14, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/29332062/cytologic-features-of-malignant-melanoma-with-osteoclast-like-giant-cells
#9
José A Jiménez-Heffernan, Magdalena Adrados, Patricia Muñoz-Hernández, Paloma Fernández-Rico, Ana I Ballesteros-García, Javier Fraga
BACKGROUND: Malignant melanoma showing numerous osteoclast-like giant cells (OGCs) is an uncommon morphologic phenomenon, rarely mentioned in the cytologic literature. The few reported cases seem to have an aggressive clinical behavior. Although most findings support monocyte/macrophage differentiation, the exact nature of OGCs is not clear. CASE: A 57-year-old woman presented with an inguinal lymphadenopathy. Sixteen years before, cutaneous malignant melanoma of the lower limb had been excised...
January 13, 2018: Acta Cytologica
https://www.readbyqxmd.com/read/29331734/in-vitro-assessment-of-silver-nanoparticles-immunotoxicity
#10
Valentina Galbiati, Laura Cornaghi, Elisabetta Gianazza, Marco A Potenza, Elena Donetti, Marina Marinovich, Emanuela Corsini
This study aimed to characterize unwanted immune effects of nanoparticles (NP) using THP-1 cells, human whole blood and enriched peripheral blood monocytes. Commercially available silver NP (AgNP < 100 nm, also confirmed by Single Particle Extinction and Scattering) were used as prototypical NP. Cells were treated with AgNP alone or in combination with classical immune stimuli (i.e. LPS, PHA, PWM) and cytokine assessed; in addition, CD54 and CD86 expression was evaluated in THP-1 cells. AgNP alone induced dose-related IL-8 production in all models, with higher response observed in THP-1 cells, possibly connected to different protein corona formation in bovine versus human serum...
January 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29331320/zika-dengue-and-yellow-fever-viruses-induce-differential-anti-viral-immune-responses-in-human-monocytic-and-first-trimester-trophoblast-cells
#11
Huanle Luo, Evandro R Winkelmann, Ildefonso Fernandez-Salas, Li Li, Sandra V Mayer, Rogelio Daniz-Lozano, Rosa Ma Sanchez-Casas, Nikos Vasilakis, Robert Tesh, Alan D Barrett, Scott C Weaver, Tian Wang
Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neonatal birth defects, but the causative mechanism is incompletely understood. ZIKV shares sequence homology and early clinical manifestations with yellow fever virus (YFV) and dengue virus (DENV) and are all transmitted in urban cycles by the same species of mosquitoes. However, YFV and DENV have been rarely reported to cause congenital diseases. Here, we compared infection with a contemporary ZIKV strain (FSS13025) to YFV17D and DENV-4 in human monocytic cells (THP-1) and first-trimester trophoblasts (HTR-8)...
January 10, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29331088/significance-of-circulatory-dpp4-activity-in-metabolic-diseases
#12
REVIEW
Titli Nargis, Partha Chakrabarti
Dipeptidyl peptidase 4 (DPP4), also known as CD26 is a type II transmembrane protein that is released from the cell membrane in a nonclassical secretory mechanism. This exopeptidase selectively degrades varieties of substrates including incretin hormones, growth factors, and cytokines. A significant detectable amount of DPP4 activity can be measured in plasma as well as in different tissues such as intestinal epithelium, vascular endothelium, lymphocytes, monocytes, kidney, liver, adipose, lung, thymus, spleen, prostate, etc...
January 13, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29331029/characterization-of-cd34-hematopoietic-cells-in-systemic-mastocytosis-potential-role-in-disease-dissemination
#13
Andrea Mayado, Cristina Teodosio, Noelia Dasilva Freire, Maria Jara-Acevedo, Andrés C Garcia-Montero, Ivan Álvarez-Twose, Laura Sánchez-Muñoz, Almudena Matito, Carolina Caldas, Javier I Muñoz-González, Ana Henriques, José I Sánchez-Gallego, Luis Escribano, Alberto Orfao
BACKGROUND: Recent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry the KIT D816V mutation in PB leukocytes. We investigated the potential association between the degree of involvement of BM hematopoiesis by the KIT D816V mutation and the distribution of different maturation-associated compartments of bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic precursors (HPC) in ISM, and identified the specific PB cell compartments that carry this mutation...
January 13, 2018: Allergy
https://www.readbyqxmd.com/read/29330445/a-novel-approach-for-correction-of-crosstalk-effects-in-pathway-analysis-and-its-application-in-osteoporosis-research
#14
Yu Zhou, Yunlong Gao, Chao Xu, Hui Shen, Qing Tian, Hong-Wen Deng
Osteoporosis is a prevalent bone metabolic disease and peripheral blood monocytes represent a major systemic cell type for bone metabolism. To identify the key dysfunctional pathways in osteoporosis, we performed pathway analyses on microarray data of monocytes from subjects with extremely high/low hip bone mineral density. We first performed a traditional pathway analysis for which different pathways were treated as independent. However, genes overlap among pathways will lead to "crosstalk" phenomenon, which may lead to false positive/negative results...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329985/the-scavenger-activity-of-the-human-p2x7-receptor-differs-from-p2x7-pore-function-by-insensitivity-to-antagonists-genetic-variation-and-sodium-concentration-relevance-to-inflammatory-brain-diseases
#15
Amber Ou, Ben J Gu, James S Wiley
Activation of P2X7 receptors is widely recognised to initiate proinflammatory responses. However P2X7 also has a dual function as a scavenger receptor which is active in the absence of ATP and plasma proteins and may be important in central nervous system (CNS) diseases. Here, we investigated both P2X7 pore formation and its phagocytic function in fresh human monocytes (as a model of microglia) by measuring ATP-induced ethidium dye uptake and fluorescent bead uptake respectively. This was studied in monocytes expressing various polymorphic variants as well as in the presence of different P2X7 antagonists and ionic media...
January 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29329953/canine-macrophages-can-like-human-macrophages-be-in-vitro-activated-toward-the-m2a-subtype-relevant-in-allergy
#16
Ina Herrmann, Jelena Gotovina, Judit Fazekas-Singer, Michael B Fischer, Karin Hufnagl, Rodolfo Bianchini, Erika Jensen-Jarolim
The M2a subtype of macrophages plays an important role in human immunoglobulin E (IgE-mediated allergies) and other Th2 type immune reactions. In contrast, very little is known about these cells in the dog. Here we describe an in-vitro method to activate canine histiocytic DH82 cells and primary canine monocyte-derived macrophages (MDMs) toward the M2a macrophages using human cytokines. For a side-by-side comparison, we compared the canine cells to human MDMs, and the human monocytic cell line U937 activated towards M1-and M2a cells on the cellular and molecular level...
January 9, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29329815/exploring-molecular-insights-into-the-interaction-mechanism-of-cholesterol-derivatives-with-the-mce4a-a-combined-spectroscopic-and-molecular-dynamic-simulation-studies
#17
Shagufta Khan, Faez Iqbal Khan, Taj Mohammad, Parvez Khan, Gulam Mustafa Hasan, Kevin A Lobb, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being considered as a potential drug target of Mycobacterium tuberculosis infection because it is required for invasion and latent survival of pathogen by utilizing host's cholesterol. In the present study, we performed molecular docking followed by 100 ns MD simulation studies to understand the mechanism of interaction of Mce4A to the cholesterol derivatives and probucol. The selected ligands, cholesterol, 25-hydroxycholesterol, 5-cholesten-3β-ol-7-one and probucol bind to the predicted active site cavity of Mce4A, and complexes remain stable during entire simulation of 100 ns...
January 9, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29329786/clinicopathological-and-prognostic-significance-of-lymphocyte-to-monocyte-ratio-in-patients-with-gastric-cancer-a-meta-analysis
#18
REVIEW
Jian-Ying Ma, Qin Liu
BACKGROUND: Recently, the lymphocyte-to-monocyte ratio (LMR) has been reported to be a prognostic factor in multiple malignancies. The current study was designed to assess the prognostic value of pretreatment LMR in gastric cancer (GC). METHODS: MEDLINE, EMBASE, Cochrane, and CNKI databases were searched until April 2017. Eligible articles were defined as studies assessing the prognostic role of pretreatment LMR in GC. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were calculated using fixed-effects or random-effects models...
January 9, 2018: International Journal of Surgery
https://www.readbyqxmd.com/read/29329608/polyphenols-isolated-from-acacia-mearnsii-bark-with-anti-inflammatory-and-carbolytic-enzyme-inhibitory-activities
#19
Jia Xiong, Mary H Grace, Debora Esposito, Slavko Komarnytsky, Fei Wang, Mary Ann Lila
The present study was designed to characterize the polyphenols isolated from Acacia mearnsii bark crude extract (B) and fractions (B1-B7) obtained by high-speed counter-current chromatography (HSCCC) and evaluate their anti-inflammatory and carbolytic enzymes (α-glucosidase and α-amylase) inhibitory activities. Fractions B4, B5, B6, B7 (total phenolics 850.3, 983.0, 843.9, and 572.5 mg·g-1, respectively; proanthocyanidins 75.7, 90.5, 95.0, and 44.8 mg·g-1, respectively) showed significant activities against reactive oxygen species (ROS), nitric oxide (NO) production, and expression of pro-inflammatory genes interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in a lipopolysaccharide (LPS)-stimulated mouse macrophage cell line RAW 264...
November 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29329563/pm2-5-induced-oxidative-stress-increases-intercellular-adhesion-molecule-1-expression-in-lung-epithelial-cells-through-the-il-6-akt-stat3-nf-%C3%AE%C2%BAb-dependent-pathway
#20
Chen-Wei Liu, Tzu-Lin Lee, Yu-Chen Chen, Chan-Jung Liang, Shu-Huei Wang, June-Horng Lue, Jaw-Shiun Tsai, Shih-Wei Lee, Shun-Hua Chen, Yi-Fan Yang, Tzu-Yi Chuang, Yuh-Lien Chen
BACKGROUND: Epidemiological studies have shown that ambient air pollution is closely associated with increased respiratory inflammation and decreased lung function. Particulate matters (PMs) are major components of air pollution that damages lung cells. However, the mechanisms remain to be elucidated. This study examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1) expression and the related mechanisms in vitro and in vivo. RESULT: The cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to A549 cells were more severely affected by treatment with O-PMs (organic solvent-extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of SRM1649b)...
January 12, 2018: Particle and Fibre Toxicology
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