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https://www.readbyqxmd.com/read/29351441/vx-809-vx-770-treatment-reduces-inflammatory-response-to-pseudomonas-aeruginosa-in-primary-differentiated-cystic-fibrosis-bronchial-epithelial-cells
#1
Manon Ruffin, Lucie Roussel, Émilie Maillé, Simon Rousseau, Emmanuelle Brochiero
Cystic fibrosis patients exhibit chronic P. aeruginosa respiratory infections and sustained pro-inflammatory state favoring lung tissue damage and remodeling, ultimately leading to respiratory failure. Loss of CFTR function is associated with MAPK hyper-activation and increased cytokines expression, such as the interleukin 8 (CXCL8). Recently, new therapeutic strategies directly targeting the basic CFTR defect have been developed and ORKAMBI (Vx-809/Vx-770 combination) is the only FDA-approved treatment for CF patients homozygous for the F508del mutation...
December 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29350771/recombinant-relaxin-protects-liver-transplants-from-ischemia-damage-via-hepatocyte-glucocorticoid-receptor-from-bench-to-bedside
#2
Shoichi Kageyama, Kojiro Nakamura, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and acute/chronic rejection as well as a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although glucocorticoid receptor (GR) signaling may enhance cytoprotective programs, clinical use of glucocorticoid is limited due to adverse effects, while clinical relevance of GR-facilitated cytoprotection in OLT remains unknown. We aimed to evaluate the significance of hepatic GR in clinical OLT and verify the impact of recombinant human relaxin (rhRLX), which may function as GR agonist in tissue/disease-specific manner...
January 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29345368/therapeutic-effect-of-lipoxin-a4-%C3%A2-in-malaria-induced-acute-lung-injury
#3
Tatiana A Pádua, Natalia D Torres, André L P Candéa, Maria Fernanda Souza Costa, Johnatas D Silva, João Luiz Silva-Filho, Fabio T M Costa, Patricia R M Rocco, Mariana C Souza, Maria G Henriques
Acute lung injury (ALI) models are characterized by neutrophil accumulation, tissue damage, alteration of the alveolar capillary membrane, and physiological dysfunction. Lipoxin A4  (LXA4 ) is an anti-inflammatory eicosanoid that was demonstrated to attenuate lipopolysaccharide-induced ALI. Experimental models of severe malaria can be associated with lung injury. However, to date, a putative effect of LXA4  on malaria (M)-induced ALI has not been addressed. In this study, we evaluated whether LXA4 exerts an effect on M-ALI...
January 3, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345065/fingolimod-targets-cerebral-endothelial-activation-to-block-leukocyte-recruitment-in-the-central-nervous-system
#4
Yawei Zhao, Dongyan Shi, Kelei Cao, Fengjiao Wu, Xingxing Zhu, Shuang Wen, Qiang You, Keqi Zhang, Lixin Liu, Hong Zhou
Fingolimod (FTY720), an immunomodulator, is approved as an oral treatment for patients with relapsing forms of multiple sclerosis. Its effects are largely attributed to its mechanism of selectively retaining lymphocytes in the lymph nodes to reduce autoreactive T-cell recruitment in the CNS. In this study, we investigated the therapeutic effect of FTY720 on an animal model of CNS inflammation induced by intracerebral ventricle LPS injection. We found that FTY720 treatment significantly prevented LPS-induced neutrophil recruitment in the CNS by inhibiting leukocyte recruitment in cerebral microvessels...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29317577/-therapeutic-effect-of-anti-cxcl1-neutralizing-antibody-on-%C3%A2-acute-ulcerative-colitis-in-mice
#5
Linglong Luo, Xuemei Zhang, Jing Wang, Xiayu Li, Jian Ma, Shourong Shen
To evaluate the therapeutic effect of CXCL1 monoclonal antibody on dextra sulfate sodium (DSS)-induced acute ulcerative colitis (UC) in mice, and to elucidate its effect on the expressions of TNF-α, IFN-γ, IL-17 and IL-10 as well as neutrophil infiltration.
 Methods: Female BALB/c mice were randomly divided into a normal group (DSS-), a disease group (DSS+saline), an anti-CXCL1 antibody group (DSS+anti-CXCL1 Ab) and a treatment control group (DSS+IgG Ab). The DSS+saline, DSS+anti-CXCL1 Ab and DSS+anti-CXCL1 Ab groups were given 3...
December 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29316242/sustained-high-fat-diet-modulates-inflammation-insulin-signalling-and-cognition-in-mice-and-a-modified-xenin-peptide-ameliorates-neuropathology-in-a-chronic-high-fat-model
#6
Paul Denver, Victor A Gault, Paula L McClean
AIMS: Metabolic disease increases risk of Alzheimer's disease and cognitive dysfunction. Chronic high fat diet (HFD) feeding leads to cognitive impairment and neuroinflammation. This study demarcated pathological events in brain as a result of short-term to chronic HFD feeding. Efficacy of Xenin-25[Lys(13)PAL] was assessed in chronic HFD-fed mice. METHODS: C57BL/6 mice were fed HFD or normal diet for 18 days, 34 days, 10 and 21 weeks. Cognition was assessed using novel object recognition and Morris water maze...
January 5, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29311111/dual-blockade-of-interleukin-1%C3%AE-and-interleukin-17a-reduces-murine-arthritis-pathogenesis-but-also-leads-to-spontaneous-skin-infections-in-non-human-primates
#7
Melanie C Ruzek, Lili Huang, Ting Ting Zhang, Shaughn Bryant, Peter F Slivka, Carolyn A Cuff, Catherine Tripp, Guenter Blaich
Despite the efficacy of biologics for treatment of rheumatoid arthritis (RA), many patients show inadequate responses and likely require neutralization of multiple mediators. Neutralization of both interleukin (IL)-1β and IL-17A with monoclonal antibodies showed greater efficacy than either agent alone in a mouse arthritis model with cooperative inhibition of key inflammatory factors, IL-6, granulocyte colony stimulating factor (G-CSF) and CXC chemokine ligand (CXCL)1. Given the potential clinical benefit in RA, we generated a human dual variable domain antibody (DVD-Ig), ABBV-615, capable of simultaneous binding and neutralization of IL-1β and IL-17A...
January 8, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29305095/a-method-for-high-transfection-efficiency-in-thp-1-suspension-cells-without-pma-treatment
#8
Xiaoren Tang, Bushra Aljahdali, Mansour Alasiri, Abdullah Bamashmous, Feng Cao, Serge Dibart, Erdjan Salih
Adherent cells such as mouse RAW cells or human cancer U2OS cells are beneficial to DNA transfection, with 20%-60% transfection efficiency. However, this DNA transfection is rarely used on suspension cells due to its low transfection efficiency (≤5%). We recently found a new DNA transfection method to increase the efficiency up to 13.5% in suspension cells without PMA treatment. We also found that DNA transfection of human TNFAIP1 or CXCL1 recombinant plasmid DNA in THP-1 cells induces a high level of TNF-α protein...
January 2, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29288512/pretreatment-of-probiotic-bifico-ameliorates-colitis-associated-cancer-in-mice-transcriptome-and-gut-flora-profiling
#9
Huan Song, Weiyi Wang, Bo Shen, Hao Jia, Zhaoyuan Hou, Ping Chen, Yunwei Sun
Individuals with inflammatory bowel disease (IBD) are at a high risk for developing colitis-associated cancer (CAC). Strategies to block the process from IBD to CAC should be considered. In the experiment, we aim to explore the chemopreventive efficacy of the probiotic cocktail Bifico and its potential mechanism in azoxymethane (AOM) and dextran sodium sulphate (DSS) induced colitis-associated cancer in mice. Oral pretreatment of Bifico was adopted to evaluate its protective effect. The colorectums of thirty-five C57BL/6 mice were collected and examined for degree of inflammation and tumorigenesis...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29283424/integrated-microrna-mrna-analysis-reveals-mir-204-inhibits-cell-proliferation-in-gastric-cancer-by-targeting-cks1b-cxcl1-and-gprc5a
#10
Sirjana Shrestha, Chi-Dung Yang, Hsiao-Chin Hong, Chih-Hung Chou, Chun-San Tai, Men-Yee Chiew, Wen-Liang Chen, Shun-Long Weng, Chung-Chu Chen, Yi-An Chang, Meng-Lin Lee, Wei-Yun Huang, Sheng-Da Hsu, Yi-Chang Chen, Hsien-Da Huang
Gastric cancer (GC) is the second most frequent cause of cancer-related deaths worldwide. MicroRNAs are single-stranded RNA molecules of 21-23 nucleotides that regulate target gene expression through specific base-pairing interactions between miRNA and untranslated regions of targeted mRNAs. In this study, we generated a multistep approach for the integrated analysis of miRNA and mRNA expression. First, both miRNA and mRNA expression profiling datasets in gastric cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) identified 79 and 1042 differentially expressed miRNAs and mRNAs, respectively, in gastric cancer...
December 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29282770/effect-of-continuous-digital-hypothermia-on-lamellar-inflammatory-signaling-when-applied-at-a-clinically-relevant-timepoint-in-the-oligofructose-laminitis-model
#11
K Dern, A van Eps, T Wittum, M Watts, C Pollitt, J Belknap
BACKGROUND: Although continuous digital hypothermia (CDH) protects lamellae from injury in the oligofructose (OF) model of sepsis-related laminitis (SRL), conflicting results exist from these studies regarding effects of CDH on lamellar inflammatory events. HYPOTHESIS/OBJECTIVES: To determine the effect of CDH on lamellar inflammatory events in normal and OF-treated horses when instituted at a clinically relevant time point (onset of clinical signs of sepsis in this model)...
December 27, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/29282312/nlrp12-mediates-adverse-neutrophil-recruitment-during-influenza-virus-infection
#12
Emma E Hornick, Balaji Banoth, Ann M Miller, Zeb R Zacharias, Nidhi Jain, Mary E Wilson, Katherine N Gibson-Corley, Kevin L Legge, Gail A Bishop, Fayyaz S Sutterwala, Suzanne L Cassel
Exaggerated inflammatory responses during influenza A virus (IAV) infection are typically associated with severe disease. Neutrophils are among the immune cells that can drive this excessive and detrimental inflammation. In moderation, however, neutrophils are necessary for optimal viral control. In this study, we explore the role of the nucleotide-binding domain leucine-rich repeat containing receptor family member Nlrp12 in modulating neutrophilic responses during lethal IAV infection. Nlrp12-/- mice are protected from lethality during IAV infection and show decreased vascular permeability, fewer pulmonary neutrophils, and a reduction in levels of neutrophil chemoattractant CXCL1 in their lungs compared with wild-type mice...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29274868/galectin-3-mediates-tumor-cell-stroma-interactions-by-activating-pancreatic-stellate-cells-to-produce-cytokines-via-integrin-signaling
#13
Wei Zhao, Jaffer A Ajani, Guha Sushovan, N Ochi, Rosa Hwang, Margarete Hafley, Randy L Johnson, Robert S Bresalier, Craig D Logsdon, Zhiqian Zhang, Shumei Song
BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is characterized by activated pancreatic stellate cells (PSCs), abundance of extracellular matrix (ECM), and production of cytokines and chemokines. Galectin 3 (GAL3), a β galactoside-specific lectin, contributes to PDAC development but its effects on the stroma and cytokine production are unclear. METHODS: The effect of recombinant human GAL3 (rGAL3) on activation of PSC, production of cytokines, and ECM proteins were determined by proliferation, invasion, cytokine array, and quantitative PCR...
December 21, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29274415/the-activation-and-function-of-il-36%C3%AE-in-neutrophilic-inflammation-in-chronic-rhinosinusitis
#14
Hai Wang, Zhi-Yong Li, Wen-Xiu Jiang, Bo Liao, Guan-Ting Zhai, Nan Wang, Zhen Zhen, Jian-Wen Ruan, Xiao-Bo Long, Heng Wang, Wei-Hong Liu, Geng-Tian Liang, Wei-Min Xu, Atsushi Kato, Zheng Liu
BACKGROUND: Although increased accumulation of neutrophils has been noted in chronic rhinosinusitis (CRS), the function and regulation of neutrophils in CRS are largely unknown. IL-36 family cytokines may play an important role in neutrophilic inflammation. OBJECTIVE: To investigate the expression and function of IL-36 cytokines in CRS. METHODS: Quantitative RT-PCR, immunohistochemistry, immunofluorescence, and ELISA were used to investigate the expression of IL-36 cytokines and IL-36 receptor (IL-36R) in sinonasal mucosa...
December 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29273051/a-role-for-b-cells-in-organic-dust-induced-lung-inflammation
#15
Jill A Poole, Ted R Mikuls, Michael J Duryee, Kristi J Warren, Todd A Wyatt, Amy J Nelson, Debra J Romberger, William W West, Geoffrey M Thiele
BACKGROUND: Agriculture organic dust exposures induce lung disease with lymphoid aggregates comprised of both T and B cells. The precise role of B cells in mediating lung inflammation is unknown, yet might be relevant given the emerging role of B cells in obstructive pulmonary disease and associated autoimmunity. METHODS: Using an established animal model, C57BL/6 wild-type (WT) and B-cell receptor (BCR) knock-out (KO) mice were repetitively treated with intranasal inhalation of swine confinement organic dust extract (ODE) daily for 3 weeks and lavage fluid, lung tissues, and serum were collected...
December 22, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29245915/curcumin-interacts-with-sildenafil-to-kill-gi-tumor-cells-via-endoplasmic-reticulum-stress-and-reactive-oxygen-nitrogen-species
#16
Jane L Roberts, Andrew Poklepovic, Laurence Booth
The present studies focused on the ability of the phosphodiesterase 5 (PDE5) inhibitor sildenafil to enhance the anti-cancer properties of clinically relevant concentrations of the dietary diarylheptanoid curcumin. In gastrointestinal tumor cells, sildenafil and curcumin interacted in a greater than additive fashion to kill. Inhibition of the extrinsic apoptotic pathway suppressed killing by ∼50%, as did blockade of the intrinsic apoptotic pathway. Sildenafil and curcumin reduced mTORC1 and mTORC2 activity and increased Beclin1 levels and the numbers of autophagosomes and autolysosomes in cells in a PERK-eIF2α-dependent fashion...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29242385/differential-regulation-of-zfp30-expression-in-murine-airway-epithelia-through-altered-binding-of-zfp148-to-rs51434084
#17
Lucas T Laudermilk, Joseph M Thomas, Samir N Kelada
Neutrophil chemotaxis to the airways is a key aspect of host response to microbes and a feature of multiple pulmonary diseases including asthma. Tight regulation of this recruitment is critical to prevent unwanted host tissue damage and inflammation. Using a mouse (Mus musculus) model of asthma applied to the Collaborative Cross (CC), we previously identified a lung gene expression quantitative trait locus (eQTL) for Zinc finger protein 30 (Zfp30) that was also a QTL for neutrophil recruitment and the hallmark neutrophil chemokine CXCL1...
December 14, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29224368/immune-response-proteins-as-predictive-biomarkers-of-doxorubicin-induced-cardiotoxicity-in-breast-cancer-patients
#18
Li-Rong Yu, Zhijun Cao, Issam Makhoul, Jaclyn R Daniels, Suzanne Klimberg, Jeanne Y Wei, Jane Pf Bai, Jinong Li, Julia T Lathrop, Richard D Beger, Valentina K Todorova
Cancer treatment with doxorubicin (DOX) can induce cumulative dose-dependent cardiotoxicity. Currently, there are no specific biomarkers that can identify patients at risk during the initial doses of chemotherapy. The aim of this study was to examine plasma cytokines/chemokines and potential cardiovascular biomarkers for the prediction of DOX-induced cardiotoxicity. Plasma samples were collected before (T0), and after the first (T1) and the second (T2) cycles of DOX-based chemotherapy of 27 breast cancer patients, including five patients who presented with >10% decline of left ventricular ejection fraction (LVEF), five patients with LVEF decline of 5-10%, and 17 patients who maintained normal LVEF at the end of chemotherapy (240 mg/m2 cumulative dose of DOX from four cycles of treatment)...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29223534/systemic-recovery-and-therapeutic-effects-of-transplanted-allogenic-and-xenogenic-mesenchymal-stromal-cells-in-a-rat-blunt-chest-trauma-model
#19
Elisa Maria Amann, Markus Thomas Rojewski, Sinja Rodi, Daniel Fürst, Jörg Fiedler, Annette Palmer, Sonja Braumüller, Markus Huber-Lang, Hubert Schrezenmeier, Rolf Erwin Brenner
BACKGROUND: Effective therapy of Acute Lung Injury (ALI) is still a major scientific and clinical problem. To define novel therapeutic strategies for sequelae of blunt chest trauma (TxT) like ALI/Acute Respiratory Distress Syndrome, we have investigated the immunomodulatory and regenerative effects of a single dose of ex vivo expanded human or rat mesenchymal stromal cells (hMSCs/rMSCs) with or without priming, immediately after the induction of TxT in Wistar rats. METHODS: We analyzed the histological score of lung injury, the cell count of the broncho alveolar lavage fluid (BAL), the change in local and systemic cytokine level and the recovery of the administered cells 24 h and 5 days post trauma...
December 6, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29209334/absence-of-the-non-signalling-chemerin-receptor-ccrl2-exacerbates-acute-inflammatory-responses-in-vivo
#20
Daniel Regan-Komito, Sophia Valaris, Theodore S Kapellos, Carlota Recio, Lewis Taylor, David R Greaves, Asif J Iqbal
Chemerin is a chemotactic protein that induces migration of several immune cells including macrophages, immature dendritic cells, and NK cells. Chemerin binds to three G protein-coupled receptors (GPCRs), including CCRL2. The exact function of CCRL2 remains unclear. CCRL2 expression is rapidly upregulated during inflammation, but it lacks the intracellular DRYLAIV motif required for classical GPCR downstream signalling pathways, and it has not been reported to internalise chemerin upon binding. The aim of this study was to investigate what role if any CCRL2 plays during acute inflammation...
2017: Frontiers in Immunology
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