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https://www.readbyqxmd.com/read/29029265/preclinical-testing-of-a-broad-spectrum-antimicrobial-endotracheal-tube-coated-with-an-innate-immune-synthetic-mimic
#1
Marjan M Hashemi, John Rovig, Jordan Bateman, Brett S Holden, Tomasz Modelzelewski, Iliana Gueorguieva, Martin von Dyck, Ronald Bracken, Carl Genberg, Shenglou Deng, Paul B Savage
Background: Endotracheal tubes provide an abiotic surface on which bacteria and fungi form biofilms, and the release of endotoxins and planktonic organisms can cause damaging inflammation and infections. Objectives: Ceragenins are small molecule mimics of antimicrobial peptides with broad-spectrum antibacterial and antifungal activity, and a ceragenin may be used to provide antimicrobial protection to the abiotic surface of an endotracheal tube. Methods: A hydrogel film, containing CSA-131, was generated on endotracheal tubes...
October 4, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28978688/rab27-dependent-exosome-production-inhibits-chronic-inflammation-and-enables-acute-responses-to-inflammatory-stimuli
#2
Margaret Alexander, Andrew G Ramstead, Kaylyn M Bauer, Soh-Hyun Lee, Marah C Runtsch, Jared Wallace, Thomas B Huffaker, Dane K Larsen, Tanya Tolmachova, Miguel C Seabra, June L Round, Diane M Ward, Ryan M O'Connell
Extracellular vesicles, including exosomes, have recently been implicated as novel mediators of immune cell communication in mammals. However, roles for endogenously produced exosomes in regulating immune cell functions in vivo are just beginning to be identified. In this article, we demonstrate that Rab27a and Rab27b double-knockout (Rab27DKO) mice that are deficient in exosome secretion have a chronic, low-grade inflammatory phenotype characterized by elevated inflammatory cytokines and myeloproliferation...
October 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28973671/pd-l1-overexpression-during-endotoxin-tolerance-impairs-the-adaptive-immune-response-in-septic-patients-via-hif1%C3%AE
#3
José Avendaño-Ortiz, Charbel Maroun-Eid, Alejandro Martín-Quirós, Víctor Toledano, Carolina Cubillos-Zapata, Paloma Gómez-Campelo, Aníbal Varela-Serrano, Jose Casas-Martin, Emilio Llanos-González, Enrique Alvarez, Francisco García-Río, Luis A Aguirre, Enrique Hernández-Jiménez, Eduardo López-Collazo
Sepsis, among other pathologies, is an endotoxin tolerance (ET)-related disease. On admission, we classified 48 patients with sepsis into 3 subgroups according to the ex vivo response to lipopolysaccharide. This response correlates with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the ET degree. Moreover, the ET-related classification determines the outcome of these patients. Programmed cell death-ligand 1 (PD-L1) expression on septic monocytes is also linked with ET status. In addition to the regulation of cytokine production, one of the hallmarks of ET that significantly affects patients with sepsis is T-cell proliferation impairment or a poor switch to the adaptive response...
July 29, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28937612/houttuynia-cordata-facilitates-metformin-on-ameliorating-insulin-resistance-associated-with-gut-microbiota-alteration-in-oletf-rats
#4
Jing-Hua Wang, Shambhunath Bose, Soo-Kyoung Lim, AbuZar Ansari, Young-Won Chin, Han Seok Choi, Hojun Kim
Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))-the same as metformin alone...
September 22, 2017: Genes
https://www.readbyqxmd.com/read/28914596/obesity-and-periodontitis-an-experimental-study-to-evaluate-the-periodontal-and-systemic-effects-of-the-co-morbidity
#5
Leire Virto, Pilar Cano, Vanesa Jiménez-Ortega, Pilar Fernández-Mateos, Jerián González, Ana Isabel Esquifino, Mariano Sanz
BACKGROUND: Obesity and overweight have been associated with periodontitis. This study aims to evaluate the periodontal and systemic effects of this association in a validated experimental model. METHODS: 28 male Wistar rats were randomly divided in four groups: control group (Con) (fed with standard diet); high-fat diet group (HFD) (fed with a diet containing 35.2% fat); control group with induced periodontitis (Con-Perio) and HFD group with induced periodontitis (HFD-Perio)...
September 15, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28910312/i%C3%AE%C2%BAk-16-decreases-mirna-155-expression-and-attenuates-the-human-monocyte-inflammatory-response
#6
Norman James Galbraith, James Burton, Mathew Brady Ekman, Joseph Kenney, Samuel Patterson Walker, Stephen Manek, Campbell Bishop, Jane Victoria Carter, Sarah Appel Gardner, Hiram C Polk
Excessive inflammatory responses in the surgical patient may result in cellular hypo-responsiveness, which is associated with an increased risk of secondary infection and death. microRNAs (miRNAs), such as miR-155, are powerful regulators of inflammatory signalling pathways including nuclear factor κB (NFκB). Our objective was to determine the effect of IκK-16, a selective blocker of inhibitor of kappa-B kinase (IκK), on miRNA expression and the monocyte inflammatory response. In a model of endotoxin tolerance using primary human monocytes, impaired monocytes had decreased p65 expression with suppressed TNF-α and IL-10 production (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28804981/lipopolysaccharide-inhibits-hepatic-gluconeogenesis-in-rats-the-role-of-immune-cells
#7
Hiroshi Tanaka, Yoshikazu Nishikawa, Toru Fukushima, Ataru Taniguchi, Yoshihito Fujita, Kinsuke Tsuda, Nobuya Inagaki, Masaya Hosokawa
AIMS/INTRODUCTION: Bacterial septicemia has diverse clinical symptoms including severe hypoglycemia. However, sepsis-induced hypoglycemia has not yet been examined in detail. The aim of the present study is to investigate the mechanisms underlying hypoglycemia in sepsis. MATERIALS AND METHODS: We induced endotoxin shock in rats using lipopolysaccharide (LPS). After an intraperitoneal injection of LPS, we measured gluconeogenesis using the pyruvate tolerance test (PTT)...
August 14, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28804726/low-dose-of-lipopolysaccharide-pretreatment-preventing-subsequent-endotoxin-induced-uveitis-is-associated-with-pi3k-akt-pathway
#8
Nan Zhang, Shuo Yu, Xinli Liu, Hong Lu
PURPOSE: To explore the effects of LPS pretreatment on endotoxin-induced uveitis and PI3K/AKT pathway. METHODS: Endotoxin-induced uveitis was induced by a single subcutaneous injection of 200 μg LPS. For the endotoxin tolerance group, induction of EIU was preceded by daily subcutaneous injection of 0.1 mg/kg LPS for five days. Clinical scores were graded at 24 h after EIU under a slit lamp microscope. HE stain was performed to observe the histopathology. Aqueous humor TNF-α concentration was quantified with enzyme-linked immunosorbent assay...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28776644/glucocorticoids-downregulate-tlr4-signaling-activity-via-its-direct-targeting-by-mir-511-5p
#9
Graziella Curtale, Tiziana A Renzi, Lorenzo Drufuca, Marcello Rubino, Massimo Locati
Endotoxin tolerance assures proper regulation of the TLR4 signaling pathway and avoids uncontrolled inflammation, limiting tissue damage and endotoxin shock development. Though underlying molecular mechanisms are still undefined, evidence indicates the involvement of microRNAs, which represent a new layer of regulation of inflammatory pathways. Here we report that LPS and other inflammatory stimuli repress miR-511-5p expression in human monocytes, while anti-inflammatory stimuli, such as TGFβ and glucocorticoids, have the opposite effect...
August 4, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28771573/human-leucocyte-antigen-hla-dr-gene-expression-is-reduced-in-sepsis-and-correlates-with-impaired-tnf%C3%AE-response-a-diagnostic-tool-for-immunosuppression
#10
Martin Sebastian Winkler, Anne Rissiek, Marion Priefler, Edzard Schwedhelm, Linda Robbe, Antonia Bauer, Corinne Zahrte, Christian Zoellner, Stefan Kluge, Axel Nierhaus
BACKGROUND: Sepsis is defined as a dysregulated immune response to infection. Impaired immune response in sepsis, often described as endotoxin tolerance, is characterized by unresponsiveness of monocytes on lipopolysaccharide (LPS) stimulation to release tumor necrosis factor α (TNFα). Furthermore, decreased monocyte surface protein expression of human leucocyte antigen DR (HLA-DR) is a marker for changes of the innate immune response during sepsis. Quantitative polymerase chain reaction (qPCR) and flow-cytometry (FACS) have been used to measure protein or gene expression of HLA-DR...
2017: PloS One
https://www.readbyqxmd.com/read/28755952/are-humans-prone-to-autoimmunity-implications-from-evolutionary-changes-in-hominin-sialic-acid-biology
#11
REVIEW
Ajit Varki
Given varied intrinsic and extrinsic challenges to the immune system, it is unsurprising that each evolutionary lineage evolves distinctive features of immunoreactivity, and that tolerance mechanisms fail, allowing autoimmunity. Humans appear prone to many autoimmune diseases, with mechanisms both genetic and environmental. Another rapidly evolving biological system involves sialic acids, a family of monosaccharides that are terminal caps on cell surface and secreted molecules of vertebrates, and play multifarious roles in immunity...
July 26, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28740170/a-galnac-gal-specific-lectin-from-the-sea-mussel-crenomytilus-grayanus-modulates-immune-response-in-macrophages-and-in-mice
#12
Oleg V Chernikov, Wei-Ting Wong, Lan-Hui Li, Irina V Chikalovets, Valentina I Molchanova, Shih-Hsiung Wu, Jiahn-Haur Liao, Kuo-Feng Hua
A GalNAc/Gal-specific lectin (CGL) from the edible mussel Crenomytilus grayanus has been demonstrated to exhibit antibacterial properties. However, the mechanism of immune modulation by CGL in mammalian cells remains unclear. Here, we demonstrated that CGL can activate immune responses in macrophages and in mice. In the in vitro cell models, CGL induced tumour necrosis factor-α and interleukin-6 secretion in mouse RAW264.7 macrophages, mouse bone marrow-derived macrophages, human THP-1 macrophages, human peripheral blood mononuclear cells and human blood monocyte-derived macrophages...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28739595/retraction-hypoxia-inducible-factor-hif-1%C3%AE-accumulation-and-hif-target-gene-expression-are-impaired-after-induction-of-endotoxin-tolerance
#13
Stilla Frede, Christian Stockmann, Sandra Winning, Patricia Freitag, Joachim Fandrey
No abstract text is available yet for this article.
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28714978/%C3%AE-ketoglutarate-orchestrates-macrophage-activation-through-metabolic-and-epigenetic-reprogramming
#14
Pu-Ste Liu, Haiping Wang, Xiaoyun Li, Tung Chao, Tony Teav, Stefan Christen, Giusy Di Conza, Wan-Chen Cheng, Chih-Hung Chou, Magdalena Vavakova, Charlotte Muret, Koen Debackere, Massimiliano Mazzone, Hsien-Da Huang, Sarah-Maria Fendt, Julijana Ivanisevic, Ping-Chih Ho
Glutamine metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the underlying mechanisms regulated by glutamine metabolism to orchestrate macrophage activation remain unclear. Here we show that the production of α-ketoglutarate (αKG) via glutaminolysis is important for alternative (M2) activation of macrophages, including engagement of fatty acid oxidation (FAO) and Jmjd3-dependent epigenetic reprogramming of M2 genes. This M2-promoting mechanism is further modulated by a high αKG/succinate ratio, whereas a low ratio strengthens the proinflammatory phenotype in classically activated (M1) macrophages...
September 2017: Nature Immunology
https://www.readbyqxmd.com/read/28674400/endotoxin-tolerance-in-mast-cells-its-consequences-for-ige-mediated-signalling-and-the-effects-of-bcl3-deficiency
#15
Magdalena Poplutz, Maryna Levikova, Juliane Lüscher-Firzlaff, Marina Lesina, Hana Algül, Bernhard Lüscher, Michael Huber
Stimulation with lipopolysaccharide (LPS; endotoxin) not only causes rapid production of proinflammatory cytokines, but also induces a state of LPS hypo-responsiveness to a second LPS stimulation (endotoxin tolerance (ET)). Murine bone marrow-derived MCs (BMMCs) and peritoneal MCs (PMCs) developed ET as shown by an abrogated production of Il6/Tnf RNAs and IL-6/TNF-α proteins. In naive BMMCs, LPS stimulation induced a transient decline in the trimethylation of lysine 9 of the core histone H3 (H3K9me3), a suppressive chromatin mark, at the Il6/Tnf promoters, which correlated with p50(NFκB) and p65(NFκB) binding...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622363/acyloxyacyl-hydrolase-promotes-the-resolution-of-lipopolysaccharide-induced-acute-lung-injury
#16
Benkun Zou, Wei Jiang, Han Han, Jing Li, Weiying Mao, Zihui Tang, Qian Yang, Guojun Qian, Jing Qian, Wenjiao Zeng, Jie Gu, Tianqing Chu, Ning Zhu, Wenhong Zhang, Dapeng Yan, Rui He, Yiwei Chu, Mingfang Lu
Pulmonary infection is the most common risk factor for acute lung injury (ALI). Innate immune responses induced by Microbe-Associated Molecular Pattern (MAMP) molecules are essential for lung defense but can lead to tissue injury. Little is known about how MAMP molecules are degraded in the lung or how MAMP degradation/inactivation helps prevent or ameliorate the harmful inflammation that produces ALI. Acyloxyacyl hydrolase (AOAH) is a host lipase that inactivates Gram-negative bacterial endotoxin (lipopolysaccharide, or LPS)...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28609207/protection-of-lipopolysaccharide-lps-preconditioning-against-endotoxin-induced-uveitis-eiu-in-rats-is-associated-with-overexpression-of-interleukin-1-receptor-associated-kinase-m-irak-m
#17
Shuo Yu, Xinli Liu, Nan Zhang, Shuo Yang, Cui Mao, Shilan Feng, Hong Lu
PURPOSE: To investigate the protective effect of LPS preconditioning against EIU in rats. METHODS: EIU in Wistar rats was developed by subcutaneous injection of LPS (200 μg). Lower dose of LPS (0.1 mg/kg, intraperitoneally) or its carrier was injected daily for five days before EIU induction. Twenty-four hours after EIU, eyes were examined and then enucleated. The degree of inflammatory reaction was determined by routine histological examinations. Real-time RT-PCR and Western blot were used to determine the activation of NF-kB and expression of IRAK-1, IRAK-4, and IRAK-M Results: Repeated pre-administration of LPS induced a significant reduction in ocular inflammation and the expression of NF-κb p65 in neurons...
June 13, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28586037/transcriptional-co-regulator-rip140-an-important-mediator-of-the-inflammatory-response-and-its-associated-diseases-review
#18
Zhu-Jun Yi, Jian-Ping Gong, Wei Zhang
The inflammatory response is a physiological process that is essential for maintaining homeostasis of the immune system. Inflammation is classified into acute inflammation and chronic inflammation, both of which pose a risk to human health. However, specific regulatory mechanisms of the inflammatory response remain to be elucidated. Receptor interacting protein (RIP) 140 is a nuclear receptor that affects an extensive array of biological and pathological processes in the body, including energy metabolism, inflammation and tumorigenesis...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28583844/nociceptin-orphanin-fq-antagonizes-lipopolysaccharide-stimulated-proliferation-migration-and-inflammatory-signaling-in-human-glioblastoma-u87-cells
#19
Andrea Bedini, Monica Baiula, Gabriele Vincelli, Francesco Formaggio, Sara Lombardi, Marco Caprini, Santi Spampinato
Glioblastoma is among the most aggressive brain tumors and has an exceedingly poor prognosis. Recently, the importance of the tumor microenvironment in glioblastoma cell growth and progression has been emphasized. Toll-like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and endogenous ligands originating from dying cells or the extracellular matrix involved in host defense and in inflammation. G-protein coupled receptors (GPCRs) have gained interest in anti-tumor drug discovery due to the role that they directly or indirectly play by transactivating other receptors, causing cell migration and proliferation...
September 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28576646/increase-in-hypothalamic-ampk-phosphorylation-induced-by-prolonged-exposure-to-lps-involves-ghrelin-and-cb1r-signaling
#20
Priscila M S Rivas, Fernanda M V Vechiato, Beatriz C Borges, Rodrigo Rorato, Jose Antunes-Rodrigues, Lucila L K Elias
Acute administration of lipopolysaccharide (LPS) from Gram-negative bacteria induces hypophagia. However, the repeated administration of LPS leads to desensitization of hypophagia, which is associated with increased hypothalamic p-AMPK expression. Because ghrelin and endocannabinoids modulate AMPK activity in the hypothalamus, we hypothesized that these neuromodulators play a role in the reversal of tolerance to hypophagia in rats under long-term exposure to LPS. Male Wistar rats were treated with single (1 LPS, 100μg/kg body weight, ip) or repeated injections of LPS over 6days (6 LPS)...
June 8, 2017: Hormones and Behavior
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