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Angela L Riffo-Campos, Azahara Fuentes-Trillo, Wan Y Tang, Zoraida Soriano, Griselda De Marco, Pilar Rentero-Garrido, Victoria Adam-Felici, Veronica Lendinez-Tortajada, Kevin Francesconi, Walter Goessler, Christine Ladd-Acosta, Montse Leon-Latre, Jose A Casasnovas, F Javier Chaves, Ana Navas-Acien, Eliseo Guallar, Maria Tellez-Plaza
We explored the association of metal levels with subclinical atherosclerosis and epigenetic changes in relevant biological pathways. Whole blood DNA Infinium Methylation 450 K data were obtained from 23 of 73 middle age men without clinically evident cardiovascular disease (CVD) who participated in the Aragon Workers Health Study in 2009 (baseline visit) and had available baseline urinary metals and subclinical atherosclerosis measures obtained in 2010-2013 (follow-up visit). The median metal levels were 7...
June 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Sebastian Heck, François Daubeuf, Duc Dung Le, Martina Sester, Dominique Bonnet, Robert Bals, Nelly Frossard, Quoc Thai Dinh
OBJECTIVE: The chemokine CXCL12 interacting with the CXC receptor 4 (CXCR4) has been reported to play a role in the development and progression of bronchial asthma, but its mechanism of action is still unknown. The objective of this study was to assess the effect of the CXCL12 neutraligand chalcone 4 on the migration of dendritic cells (DCs) in a murine model of allergic airway inflammation. METHODS: A 21-day ovalbumin (OVA)-induced allergic-airway TH2 inflammation model in BALB/c mice was used...
April 20, 2018: Neuroimmunomodulation
Jeremiah D Heredia, Jihye Park, Riley J Brubaker, Steven K Szymanski, Kevin S Gill, Erik Procko
Chemokine receptors CXCR4 and CCR5 regulate WBC trafficking and are engaged by the HIV-1 envelope glycoprotein gp120 during infection. We combine a selection of human CXCR4 and CCR5 libraries comprising nearly all of ∼7000 single amino acid substitutions with deep sequencing to define sequence-activity landscapes for surface expression and ligand interactions. After consideration of sequence constraints for surface expression, known interaction sites with HIV-1-blocking Abs were appropriately identified as conserved residues following library sorting for Ab binding, validating the use of deep mutational scanning to map functional interaction sites in G protein-coupled receptors...
April 20, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Denisa Baci, Antonino Bruno, Barbara Bassani, Matilde Tramacere, Lorenzo Mortara, Adriana Albini, Douglas M Noonan
Carnitines play an important role in the energy exchange in cells, involved in the transport of fatty acids across the inner mitochondrial membrane. L-Acetylcarnitine (ALCAR) is an acetic acid ester of carnitine that has higher bioavailability than carnitine and is considered a fat-burning energizer supplement. We previously found that in serum samples from prostate cancer (PCa) patients, 3 carnitine family members were significantly decreased, suggesting a potential protective role of carnitine against PCa...
April 17, 2018: Cancer Letters
Geoffrey Lee, Ana Isabel Espirito Santo, Stefan Zwingenberger, Lawrence Cai, Thomas Vogl, Marc Feldmann, Nicole J Horwood, James K Chan, Jagdeep Nanchahal
A major discovery of recent decades has been the existence of stem cells and their potential to repair many, if not most, tissues. With the aging population, many attempts have been made to use exogenous stem cells to promote tissue repair, so far with limited success. An alternative approach, which may be more effective and far less costly, is to promote tissue regeneration by targeting endogenous stem cells. However, ways of enhancing endogenous stem cell function remain poorly defined. Injury leads to the release of danger signals which are known to modulate the immune response, but their role in stem cell-mediated repair in vivo remains to be clarified...
April 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Saleem Ullah Shahid, N A Shabana, Abdul Rehman, Steve Humphries
BACKGROUND: Coronary artery disease (CAD) remains the single most important cause of mortality worldwide. Many candidate and GWAS genetic variants have been identified in the recent years. In the current study, we selected six SNPs from various genes that have originally been identified in GWAS studies and examined the association of SNPs individually and as a genetic risk score (GRS) with CAD and blood lipid levels in the Pakistani subjects. METHODS: Six hundred twenty-four (404 cases and 219 controls) subjects were genotyped for variants rs10757274 in CDKN2A gene, rs17465637 in MIA3 gene, rs7025486 in DAB2IP gene, rs17228212 in SMAD3 gene, rs981887 in MRAS gene and rs1746048 in CXCL12 gene, by TaqMan and KASPar allele discrimination techniques...
April 19, 2018: Lipids in Health and Disease
Pierre Nicolle, Hong Liang, Elodie Reboussin, Ghislaine Rabut, Elise Warcoin, Françoise Brignole-Baudouin, Stéphane Melik-Parsadaniantz, Christophe Baudouin, Antoine Labbe, Annabelle Reaux-Le Goazigo
Dry eye symptoms are among the leading complaints in ophthalmology. Dry eye disease (DED) is associated with significant pain affecting quality of life. Cellular and molecular mechanisms underlying ocular pain associated with DED are not fully understood. In this study, we investigated the ocular surface of patients with DED using in vivo confocal microscopy (IVCM) to quantify corneal nerve density and its relation with corneal inflammation. Gene expression of the proinflammatory markers HLA-DR, IL-6, CXCL12, and CCL2 and the receptors CXCR4 and CCR2, as well as PENK (enkephalin precursor), was therefore quantified in conjunctival impression cytology specimens...
April 17, 2018: International Journal of Molecular Sciences
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
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
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
Shabnam Hemmati-Sadeghi, Pradip Dey, Jochen Ringe, Rainer Haag, Michael Sittinger, Tilo Dehne
This study aimed to evaluate the potential of an anti-inflammatory polyethylene glycol (PEG) hydrogel for osteoarthritis (OA) management in an OA in vitro model. Freshly isolated porcine chondrocytes were maintained in high-density cultures to form cartilage-like three-dimensional micromasses. Recombinant porcine tumor necrosis factor-alpha (TNF-α) was used to induce OA-like changes. Normal and OA-like micromasses were treated with dendritic polyglycerol sulfate-based PEG hydrogel. Live/dead staining showed that all micromasses remained vital and presented similar morphological characteristics...
April 16, 2018: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
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
Michael Simoni, Hugh S Taylor
PURPOSE OF REVIEW: The current review provides an update on recent advances in stem cell biology relevant to female reproduction. RECENT FINDINGS: Stem cells are undifferentiated cells that often serve as a reservoir of cells to regenerate tissue in settings or injury or cell loss. The endometrium has progenitor stem cells that can replace all of the endometrium during each menstrual cycle. In addition, multipotent endometrial cells replace these progenitor cells when depleted...
April 12, 2018: Current Opinion in Obstetrics & Gynecology
Frank M Davis, Katherine Gallagher
Chronic nonhealing wounds represent a significant clinical problem and cost the healthcare system $19 billion annually. Recently, Vågesjö et al. (2018) demonstrated a promising therapeutic approach for nonhealing wounds with topical application of CXCL12-producing Lactobacilli that enhanced healing through alterations in the wound microenvironment.
April 11, 2018: Cell Host & Microbe
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
Julia Ney, Katleen Hoffmann, Patrick Meybohm, Andreas Goetzenich, Sandra Kraemer, Carina Benstöm, Nina C Weber, Johannes Bickenbach, Rolf Rossaint, Gernot Marx, Kai Zacharowski, Jürgen Bernhagen, Christian Stoppe
In contrast to several smaller studies, which demonstrate that remote ischemic preconditioning (RIPC) reduces myocardial injury in patients that undergo cardiovascular surgery, the RIPHeart study failed to demonstrate beneficial effects of troponin release and clinical outcome in propofol-anesthetized cardiac surgery patients. Therefore, we addressed the potential biochemical mechanisms triggered by RIPC. This is a predefined prospective sub-analysis of the randomized and controlled RIPHeart study in cardiac surgery patients ( n = 40) that was recently published...
April 5, 2018: International Journal of Molecular Sciences
Fang Yuan, Shuang Chang, Longlong Luo, Yaning Li, Liping Wang, Yaying Song, Meijie Qu, Zhijun Zhang, Guo-Yuan Yang, Yongting Wang
Oligodendrocyte precursor cells (OPCs) are needed for white matter repair after various brain injury. Means that promote OPC functions could benefit white matter recovery after injury. Chemokine CXCL12 and endothelial progenitor cells (EPCs) both have been shown to promote remyelination. We hypothesize that the beneficial effects of EPCs and CXCL12 can be harnessed by genetically modifying EPCs with cxcl12 to synergistically improve the functions of OPCs. In this work, CXCL12-EPC was generated using virus-mediated gene transfer...
March 31, 2018: Experimental Cell Research
Haruka Sekiguchi, Tomoko Kuroyanagi, David Rhainds, Kazuya Kobayashi, Yuka Kobayashi, Hiroaki Ohno, Nikolaus Heveker, Kenichi Akaji, Nobutaka Fujii, Shinya Oishi
The atypical chemokine receptor 3 (ACKR3)/CXC chemokine receptor 7 (CXCR7) recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12 and is involved in a number of physiological and pathological processes. Here, we investigated the SAR of the component amino acids in a ACKR3-selective ligand, FC313 [cyclo(-D-Tyr-L-Arg-L-MeArg-L-Nal(2)-L-Pro-)], for the devel-opment of highly active ACKR3 ligands. Notably, modification at the L-Pro position with a bulky hydrophobic side chain led to improved bioactivity toward ACKR3...
April 2, 2018: Journal of Medicinal Chemistry
Rafet Ameti, Serena Melgrati, Egle Radice, Elisabetta Cameroni, Elin Hub, Sylvia Thelen, Antal Rot, Marcus Thelen
Chemokines, small chemotactic cytokines, orchestrate cell migration by binding to their cognate chemokine receptors. While chemokine-mediated stimulation of typical G-protein-coupled chemokine receptors leads to cell migration, binding of chemokines to atypical chemokine receptors (ACKRs) does not induce canonical signaling. ACKRs are considered important chemokine scavengers, that can create gradients which help direct cells to sites of inflammation or to their immunological niches. Synthetic chemokines have been used in the past to study and decode chemokine-receptor interactions...
March 30, 2018: Journal of Leukocyte Biology
Yuko Kitawaki, Yasuhiro Nakamura, Fumie Kubota-Nakayama, Yuto Yamazaki, Yasuhiro Miki, Shuko Hata, Kazue Ise, Kumi Kikuchi, Ryo Morimoto, Fumitoshi Satoh, Hironobu Sasano
The tumor microenvironment plays pivotal roles in various human neoplasms. However, that of benign tumor, particularly hormone-secreting endocrine tumors, has remained virtually unknown. Therefore, we firstly attempted to analyze the tumor microenvironment of autonomous hormone-secreting adrenocortical adenomas. We first histologically evaluated 21 cortisol-producing adrenocortical adenoma (CPA) and 13 aldosterone-producing adrenocortical adenoma (APA) cases. Quantitative histological analysis revealed that intratumoral immune cell infiltration (ICI) was more pronounced in CPAs than APAs...
March 26, 2018: Human Pathology
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