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sepsis AND anti-inflammatory

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https://www.readbyqxmd.com/read/28724977/therapeutic-targeting-of-hmgb1-during-experimental-sepsis-modulates-the-inflammatory-cytokine-profile-to-one-associated-with-improved-clinical-outcomes
#1
Natalie E Stevens, Marianne J Chapman, Cara K Fraser, Tim R Kuchel, John D Hayball, Kerrilyn R Diener
Sepsis remains a significant health burden and a major clinical need exists for therapeutics to dampen the excessive and uncontrolled immune activation. Nuclear protein high mobility group box protein 1 (HMGB1) is released following cell death and is a late mediator in sepsis pathogenesis. While approaches targeting HMGB1 have demonstrated reduced mortality in pre-clinical models of sepsis, the impact of HMGB1 blockade on the complex septic inflammatory milieu and the development of subsequent immunosuppression remain enigmatic...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714582/altered-levels-of-soluble-cd18-may-associate-immune-mechanisms-with-outcome-in-sepsis
#2
Tue Wenzel Kragstrup, Kristian Juul-Madsen, Stig Hill Christiansen, Xianwei Zhang, Jan Krog, Thomas Vorup-Jensen, Anders Gade Kjaergaard
The pathogenesis of sepsis involves a dual inflammatory response, with a hyper-inflammatory phase followed by, or in combination with, a hypo-inflammatory phase. The adhesion molecules LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) support leukocyte adhesion to intercellular adhesion molecules and phagocytosis through complement opsonisation, both processes relevant to the immune response during sepsis. Here, we investigate the role of soluble (s)CD18 in sepsis with emphasis on sCD18 as a mechanistic biomarker of immune reactions and outcome of sepsis...
July 17, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28713932/human-trypsin-inhibitor-reduces-the-apoptosis-of-lipopolysaccharide%C3%A2-induced-human-kidney%C3%A2-2-cells-by-promoting-mitochondrial-fusion
#3
Ning Liu, Zhiyi Jiang, Yongjun Liu, Yao Nie, Juan Chen, Bin Ouyang, Xiangdong Guan, Minying Chen
Imbalance in mitochondrial fusion/fission is one of the mechanisms leading to sepsis‑induced mitochondrial dysfunction and cell apoptosis. The present study examined the effects of human trypsin inhibitor (UTI), a well‑known antioxidant and anti‑inflammatory substance, on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)‑induced human kidney‑2 (HK‑2) cells. The HK‑2 cells were incubated for 24 h either with LPS (800 ng/ml) or LPS (800 ng/ml) mixed with UTI (250 U/ml). Cell viability was assessed using a3‑(4,5‑dimethyl‑2‑thiazolyl)‑2, 5‑diphenyl‑2‑H‑tetrazolium bromide assay...
July 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28704709/protective-role-of-surface-toll-like-receptor-9-expressing-neutrophils-in-local-inflammation-during-systemic-inflammatory-response-syndrome-in-mice
#4
Xiuping Meng, Wei Sun, Yunjia Ren, Yue Xiao, Peiyan Zhao, Wenting Lu, Li Hua, Luowei Wang, Liying Wang, Yongli Yu
Clinically, systemic inflammatory response syndrome (SIRS) occurs after serious trauma or sepsis. In sepsis, neutrophils are the major effector cells responsible for eliminating pathogens. However, the role of neutrophils in development of SIRS, especially in local inflammatory area, is controversial. In this study, we established a SIRS mouse model characterized with cytokine-mediated lethal shock by intraperitoneal injection of oligodexynucleotides containing CpG motifs (CpG ODN) in D-galactosamine (D-GalN) sensitized mice based on our previous work and found that abundant neutrophils were rapidly recruited into the peritoneal cavity, where some neutrophils expressed surface TLR9 (sTLR9), defined as sTLR9(+) neutrophils...
July 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28701511/n-arachidonoyl-dopamine-modulates-acute-systemic-inflammation-via-nonhematopoietic-trpv1
#5
Samira K Lawton, Fengyun Xu, Alphonso Tran, Erika Wong, Arun Prakash, Mark Schumacher, Judith Hellman, Kevin Wilhelmsen
N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28697503/update-of-sepsis-in-the-intensive-care-unit
#6
Kelly Roveran Genga, James A Russell
Sepsis, the most common cause of admission to an intensive care unit (ICU), has had an increased incidence and prevalence over the last years with a simultaneous decrease in its short-term mortality. Sepsis survivors are more frequently discharged from hospital and often experience long-term outcomes such as late mortality, immune dysfunction, secondary infections, impaired quality of life, and unplanned readmissions. Early recognition and management of sepsis have challenged emergency care and critical care physicians and nurses...
July 12, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28694452/phosphatidylserine-mediated-platelet-clearance-by-endothelium-decreases-platelet-aggregates-and-procoagulant-activity-in-sepsis
#7
Ruishuang Ma, Rui Xie, Chengyuan Yu, Yu Si, Xiaoming Wu, Lu Zhao, Zhipeng Yao, Shaohong Fang, He Chen, Valerie Novakovic, Chunyan Gao, Junjie Kou, Yayan Bi, Hemant S Thatte, Bo Yu, Shufen Yang, Jin Zhou, Jialan Shi
The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692671/immune-profiles-and-clinical-outcomes-between-sepsis-patients-with-or-without-active-cancer-requiring-admission-to-intensive-care-units
#8
Wen-Feng Fang, Yu-Mu Chen, Chiung-Yu Lin, Kuo-Tung Huang, Hsu-Ching Kao, Ying-Tang Fang, Chi-Han Huang, Ya-Ting Chang, Yi-His Wang, Chin-Chou Wang, Meng-Chih Lin
BACKGROUND: Immunoparalysis was observed in both patients with cancer and sepsis. In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death protein 1/programmed death-ligand 1 axis are two key components of immunoparalysis. Several emerging therapies against these two axes gained significant clinical benefit. In severe sepsis patients, immunoparalysis was known as compensatory anti-inflammatory response syndrome and this has been suggested as an important cause of death in patients with sepsis...
2017: PloS One
https://www.readbyqxmd.com/read/28692111/a-randomised-trial-on-the-effect-of-anti-platelet-therapy-on-the-systemic-inflammatory-response-in-human-endotoxaemia
#9
Dorien Kiers, Wouter A van der Heijden, Lisa van Ede, Jelle Gerretsen, Quirijn de Mast, André J van der Ven, Saloua El Messaoudi, Gerard A Rongen, Marc Gomes, Matthijs Kox, Peter Pickkers, Niels P Riksen
The use of acetylsalicylic acid (ASA) is associated with improved outcome in patients with sepsis, and P2Y12 inhibitors have been suggested to also have immunomodulatory effects. Therefore, we evaluated the effects of clinically relevant combinations of antiplatelet therapy on the immune response in experimental endotoxaemia in humans in vivo. Forty healthy subjects were randomised to seven days of placebo, placebo with ASA, ticagrelor and ASA, or clopidogrel and ASA treatment. Systemic inflammation was elicited at day seven by intravenous administration of Escherichia coli endotoxin...
July 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28691814/intervention-of-dietary-dipeptide-gamma-l-glutamyl-l-valine-%C3%AE-ev-ameliorates-inflammatory-response-in-a-mouse-model-of-lps-induced-sepsis
#10
MacKenzie E Chee, Kaustav Majumder, Yoshinori Mine
Sepsis, the systemic inflammatory response syndrome (SIRS) with infection is one of the leading causes of death in critically ill patients in the developed world due to the lack of effective antisepsis treatments. This study examined the efficacy of dietary dipeptide gamma-l-glutamyl-l-valine (γ-EV), which was characterized previously as an anti-inflammatory peptide, in an LPS-induced mouse model of sepsis. BALB/c mice were administered γ-EV via oral gavage followed by an intraperitoneal injection of LPS to induce sepsis...
July 10, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28690060/genetically-modified-lactococcus-lactis-producing-a-green-fluorescence-protein-bovine-lactoferrin-fusion-protein-suppresses-proinflammatory-cytokine-expression-in-lipopolysaccharide-stimulated-raw-264-7-cells
#11
S Shigemori, F Namai, Y Yamamoto, S Nigar, T Sato, T Ogita, T Shimosato
Lactoferrin (LF), an iron-binding glycoprotein distributed widely in the biological fluids of mammals, is believed to play an important role in host defenses against infection. Previous studies in animal models and humans demonstrated that combined administration of LF and probiotic lactic acid bacteria (LAB) can prevent sepsis. In this study, we genetically engineered a probiotic LAB strain, Lactococcus lactis, to produce recombinant bovine LF based on the green fluorescence protein (GFP)-fused expression system...
July 6, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28688914/glucagon-and-glucagon-like-peptide-1-as-novel-anti-inflammatory-and-immunomodulatory-compounds
#12
REVIEW
Daniella B R Insuela, Vinicius F Carvalho
Glucagon and glucagon-like peptide-1 (GLP-1) are polypeptide hormones that are produced by pancreatic α-cells and the intestine, respectively, whose main function is to control glucose homeostasis. The glucagon and GLP-1 levels are imbalanced in diabetes. Furthermore, type 1diabetic patients and animals present with a diminished inflammatory response, which is related to some morbidities of diabetes, such as a higher incidence of infectious diseases, including sepsis. The focus of this review is to briefly summarize the state of the art concerning the effects of glucagon and GLP-1 on the inflammatory response...
July 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28679406/the-common-promoter-polymorphism-rs11666254-downregulates-fpr2-alx-expression-and-increases-risk-of-sepsis-in-patients-with-severe-trauma
#13
Han Zhang, Yao Lu, Guixiang Sun, Fang Teng, Nian Luo, Jianxin Jiang, Aiqing Wen
BACKGROUND: Formyl peptide receptor 2-lipoxin receptor (FPR2/ALX) modulates the anti-inflammatory response and therefore may be a target for treating sepsis. The purpose of this study was to investigate the association between genetic variants of the FPR2/ALX gene and sepsis after severe trauma as well as to further analyze the functions of sepsis-related genetic polymorphisms. METHODS: Three tag single-nucleotide polymorphisms (tag SNPs) that captured all common alleles across the FPR2/ALX genomic region were genotyped using pyrosequencing in an initial sample consisting of 275 patients with severe trauma...
July 6, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28662100/mir-146a-mir-146b-and-mir-155-increase-expression-of-il-6-and-il-8-and-support-hsp10-in-an-in-vitro-sepsis-model
#14
Dagmar Pfeiffer, Eva Roßmanith, Ingrid Lang, Dieter Falkenhagen
microRNAs (miRNAs) play an essential role in inflammation processes including sepsis. This study aimed to identify miRNAs as candidates for therapies that are involved in the innate immune response and to assess their potential functions in the activation of the endothelium. We stimulated THP-1 monocytes with 10 ng/ml LPS for 4 h and used the supernatant for the stimulation of human umbilical vein endothelial cells (HUVEC) or human pulmonary microvascular endothelial cells (HPMEC) for 16 h. miRNA array analysis (of 1,891 miRNAs) identified a 1...
2017: PloS One
https://www.readbyqxmd.com/read/28648331/il-35-as-a-newly-proposed-homeostasis-associated-molecular-pattern-plays-three-major-functions-including-anti-inflammatory-initiator-effector-and-blocker-in-cardiovascular-diseases
#15
Xinyuan Li, Pu Fang, William Y Yang, Hong Wang, Xiaofeng Yang
IL-35 is a new anti-inflammatory cytokine identified in 2007, which inhibits inflammation and immune responses by inducing regulatory T cells and regulatory B cells and suppressing effector T cells and macrophages. The unique initiator and effector anti-inflammatory properties of IL-35 bring tremendous interest in investigating its role during cardiovascular disease (CVD) development, in which inflammatory processes are firmly established as central to its development and complications. In this review, we update recent understanding of how IL-35 is produced and regulated in the cells...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28646428/effects-of-carvacrol-on-survival-mesenteric-blood-flow-aortic-function-and-multiple-organ-injury-in-a-murine-model-of-polymicrobial-sepsis
#16
Erdem Kamil Ozer, Mustafa Tugrul Goktas, Aysun Toker, Hulagu Bariskaner, Ceyhan Ugurluoglu, Alper Bektas Iskit
Carvacrol (CRV) has strong cytoprotective, antioxidant, and anti-inflammatory properties. We aimed to demonstrate the possible protective effects of CRV on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wistar rats were allocated into the following four groups: Sham, CLP, Sham + CRV, and CLP + CRV. The animals were orally administered with CRV (80 mg/kg/day) or vehicle (corn oil; 1 mL/kg/day) for 7 days...
June 23, 2017: Inflammation
https://www.readbyqxmd.com/read/28637971/esculentoside-a-ameliorates-cecal-ligation-and-puncture-induced-acute-kidney-injury-in-rats
#17
Guodong Sun, Wei Yang, Yang Zhang, Mingyan Zhao
Esculentoside A (EsA), a saponin isolated from Phytolacca esculenta, can attenuate acute liver and lung injury. However, whether EsA has a protective effect against sepsis-induced acute kidney injury (AKI) has not been reported. In this study, EsA (2.5, 5, or 10 mg/kg) was given to rats with sepsis induced by cecal ligation and puncture (CLP). We found that EsA improved the survival of septic rats in a dose-dependent manner. In addition, EsA lowered the kidney tubular damage score and decreased blood urea nitrogen and creatinine...
June 22, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28634421/the-role-of-von-willebrand-factor-in-vascular-inflammation-from-pathogenesis-to-targeted-therapy
#18
REVIEW
Felice Gragnano, Simona Sperlongano, Enrica Golia, Francesco Natale, Renatomaria Bianchi, Mario Crisci, Fabio Fimiani, Ivana Pariggiano, Vincenzo Diana, Andreina Carbone, Arturo Cesaro, Claudia Concilio, Giuseppe Limongelli, Mariagiovanna Russo, Paolo Calabrò
Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28628607/host-gene-expression-analysis-in-sri-lankan-melioidosis-patients
#19
Shivankari Krishnananthasivam, Nimanthi Jayathilaka, Harindra Darshana Sathkumara, Enoka Corea, Mohan Natesan, Aruna Dharshan De Silva
BACKGROUND: Melioidosis is a life threatening infectious disease caused by the gram-negative bacillus Burkholderia pseudomallei predominantly found in southeast Asia and northern Australia. Studying the host transcription profiles in response to infection is crucial for understanding disease pathogenesis and correlates of disease severity, which may help improve therapeutic intervention and survival. The aim of this study was to analyze gene expression levels of human host factors in melioidosis patients and establish useful correlation with disease biomarkers, compared to healthy individuals and patients with sepsis caused by other pathogens...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28625271/-advances-in-immunotherapeutic-research-of-sepsis
#20
Lihua Dong, Juan Lyu, Lili Ding, Zhongmin Liu
Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Despite decades of research, it remains the leading cause of death in intensive care units (ICUs). None of the current treatment, including antibiotics, organ protection and liquid resuscitation, is specifically effective for sepsis. Immunosuppression is one of the currently accepted pathogenesis and immunotherapy is one of the hot spot of current sepsis research. Immune related treatments include restricting the release of pathogen toxin and its removal, controlling the excessive inflammatory reaction and apoptosis inhibition, etc...
February 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
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