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https://www.readbyqxmd.com/read/29470247/hypofibrinogenemia-is-associated-with-poor-outcome-and-secondary-hemophagocytic-lymphohistiocytosis-macrophage-activation-syndrome-in-pediatric-severe-sepsis
#1
Jessica K Signoff, Julie C Fitzgerald, David T Teachey, Fran Balamuth, Scott L Weiss
OBJECTIVES: Some children with sepsis exhibit a sustained hyperinflammatory response that can trigger secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Although hypofibrinogenemia is a shared feature of sepsis and hemophagocytic lymphohistiocytosis, there are no data about fibrinogen as a biomarker to identify children with sepsis/secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome overlap. We hypothesized that hypofibrinogenemia is associated with poor outcomes and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome and has utility as a screening biomarker for this sepsis phenotype...
February 21, 2018: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/29468593/methods-to-study-the-innate-immune-response-to-sepsis
#2
Wendy E Walker
This chapter describes techniques to measure the innate immune response in the mouse cecal ligation and puncture model of sepsis. The reader will learn how to perform retro-orbital bleeds to harvest serum from mice and learn how to perform peritoneal lavage to harvest cells and inflammatory mediators from this compartment. The enzyme-linked immunosorbent assay (ELISA) technique is described as a method to measure the levels of cytokines and chemokines in these fluids. Additionally, this chapter describes techniques to stain the cellular fraction of the peritoneal lavage with fluorescently labeled antibodies, and perform fluorescence activated cell sorting (FACS) to quantify macrophages and neutrophils in this compartment...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29466778/new-md2-inhibitors-derived-from-curcumin-with-improved-anti-inflammatory-activity
#3
Yali Zhang, Zhiguo Liu, Jianzhang Wu, Bin Bai, Hongjin Chen, Zhongxiang Xiao, Lingfeng Chen, Yunjie Zhao, Hazel Lum, Yi Wang, Hong Zhang, Guang Liang
An overactive Toll-like receptor (TLR) signaling complex is a significant pathogenic factor of acute and chronic inflammatory diseases. The natural product curcumin is reported to inhibit the TLR4 co-receptor, MD2 (myeloid differentiation protein 2), but its low in vivo bioavailability limits its therapeutic potential. We developed new curcumin analogs (MACs) with removal of the β-diketone moiety and substituted residues in benzene rings, and identify these as potential MD2 inhibitors with improved inhibition potency and stability over that of curcumin...
February 15, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29466000/python-cathelicidin-cathpb1-protects-against-multidrug-resistant-staphylococcal-infections-by-antimicrobial-immunomodulatory-duality
#4
Shasha Cai, Xue Qiao, Lan Feng, Nannan Shi, Hui Wang, Huaixin Yang, Zhilai Guo, Mengke Wang, Yan Chen, Yipeng Wang, Haining Yu
Multidrug-resistant Staphylococcus aureus, including MRSA (Methicillin-Resistant) and VRSA (Vancomycin-resistant), causes serious healthcare-associated infections, even sepsis and death. Here, we identified six novel cathelicidins (CATHPb1-6) from Python bivittatu, and CATHPb1 displayed the best in vitro pharmacological and toxicological profile. We further show that CATHPb1 exhibited evident protection in mice MRSA/VRSA infection models, either given 24h before or 4h after infection. The protection was all effective through different administration routes, but was blocked by in vivo depletion of monocyte/macrophages or neutrophils...
February 21, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29455288/mycophenolate-mofetil-protects-septic-mice-via-the-dual-inhibition-of-inflammatory-cytokines-and-pd-1
#5
Shun-Wei Huang, Hao Chen, Mei-Ling Lu, Jin-Long Wang, Rong-Li Xie, Bing Zhao, Ying Chen, Zhi-Wei Xu, Jian Fei, En-Qiang Mao, Er-Zhen Chen
Due to the imbalance between hyper-inflammation and hypo-inflammation, which are characterized by excessive cytokine productions and programmed death 1 (PD-1) upregulation, respectively, sepsis remains a highly lethal inflammatory syndrome with limited effective therapies. Mycophenolate mofetil (MMF), an immunosuppressant, has been reported to attenuate various inflammatory diseases. However, the role of MMF in sepsis therapy remains to be elucidated. C57BL-6J mice underwent cecal ligation and puncture (CLP) and were treated either with or without MMF...
February 17, 2018: Inflammation
https://www.readbyqxmd.com/read/29449936/function-of-aquaporins-in-sepsis-a-systematic-review
#6
REVIEW
Katharina Rump, Michael Adamzik
Background: Sepsis is a common cause of death in intensive care units worldwide. Due to the high complexity of this immunological syndrome development of novel therapeutic strategies is urgent. Promising drug targets or biomarkers may depict aquaporins (AQPs) as they regulate crucial key mechanisms of sepsis. Main body: Here we report on base of the current literature that several AQPs are involved in different physiological processes of sepsis. In immune system mainly AQPs 3, 5 and 9 seem to be important, as they regulate the migration of different immune cells...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29443058/two-photon-intravital-imaging-of-leukocytes-during-the-immune-response-in-lipopolysaccharide-treated-mouse-liver
#7
Sang A Park, Young Ho Choe, Sung Hwan Lee, Young-Min Hyun
Sepsis is a type of severe infection that can cause organ failure and tissue damage. Although the mortality and morbidity rates associated with sepsis are extremely high, no direct treatment or organ-related mechanism has been examined in detail in real time. The liver is the key organ that manages toxins and infections in the human body. Herein, we aimed to perform intravital imaging of mouse liver after induction of endotoxemia in order to track the motility of immune cells, such as neutrophils and liver capsular macrophages (LCMs)...
February 6, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29437578/tissue-factor-an-essential-mediator-of-hemostasis-and-trigger-of-thrombosis
#8
REVIEW
Steven P Grover, Nigel Mackman
Tissue factor (TF) is the high-affinity receptor and cofactor for FVII/VIIa. The TF-FVIIa complex is the primary initiator of blood coagulation and plays an essential role in hemostasis. TF is expressed on perivascular and epithelial cells at organ and body surfaces where it forms a hemostatic barrier. TF also provides additional hemostatic protection to vital organs, such as the brain, lung, and heart. Under pathological conditions, TF can trigger both arterial and venous thrombosis. For instance, atherosclerosis plaques contain high levels of TF on macrophage foam cells and microvesicles that drives thrombus formation after plaque rupture...
February 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29434211/a-cold-inducible-rna-binding-protein-cirp-derived-peptide-attenuates-inflammation-and-organ-injury-in-septic-mice
#9
Fangming Zhang, Max Brenner, Weng-Lang Yang, Ping Wang
Cold-inducible RNA-binding protein (CIRP) is a novel sepsis inflammatory mediator and C23 is a putative CIRP competitive inhibitor. Therefore, we hypothesized that C23 can ameliorate sepsis-associated injury to the lungs and kidneys. First, we confirmed that C23 dose-dependently inhibited TNF-α release, IκBα degradation, and NF-κB nuclear translocation in macrophages stimulated with CIRP. Next, we observed that male C57BL/6 mice treated with C23 (8 mg/kg BW) at 2 h after cecal ligation and puncture (CLP) had lower serum levels of LDH, ALT, IL-6, TNF-α, and IL-1β (reduced by ≥39%) at 20 h after CLP compared with mice treated with vehicle...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29432911/tephrosin-attenuates-sepsis-induced-acute-lung-injury-in-rats-by-impeding-expression-of-icam-1-and-mip-2
#10
Jiaorong Yang, Helan Tian, Xiaomo Huang
Acute lung injury (ALI), a devastating form of respiratory infections, is characterized by increased edema, release of cytokines, weakened arterial oxygenation and infiltration of neutrophils and lymphocytes. The objective of the research envisaged was to reveal protective effects of tephrosin (TP) in ALI. In the present investigation, sepsis was triggered in rats by cecal ligation and puncture (CLP) method, and TP was administered intraperitonially. Five groups - Group A (control), Group B (Sham group) Group C (infected and untreated), and Group D and E (infected and treated with 25 and 50 mg/kg TP respectively) - of ten rats each, were used for the investigation...
February 9, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29431121/methotrexate-limits-inflammation-through-an-a20-dependent-cross-tolerance-mechanism
#11
Cristina Municio, Ángeles Dominguez-Soto, Sara Fuentelsaz-Romero, Amalia Lamana, Nuria Montes, Víctor D Cuevas, Raquel García Campos, José L Pablos, Isidoro González-Álvaro, Amaya Puig-Kröger
OBJECTIVES: Methotrexate (MTX) is the anchor drug for treatment of rheumatoid arthritis (RA), but the mechanism of its anti-inflammatory action is not fully understood. In RA, macrophages display a proinflammatory polarisation profile that resembles granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated macrophages and the response to MTX is only observed in thymidylate synthase+ GM-CSF-dependent macrophages. To determine the molecular basis for the MTX anti-inflammatory action, we explored toll-like receptor (TLR), RA synovial fluid (RASF) and tumour necrosis factor receptor (TNFR)-initiated signalling in MTX-exposed GM-CSF-primed macrophages...
February 3, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29428804/links-between-a-biomarker-profile-cold-ischaemic-time-and-clinical-outcome-following-simultaneous-pancreas-and-kidney-transplantation
#12
Hussein A Khambalia, M Yvonne Alexander, Mahesan Nirmalan, Ria Weston, Phillip Pemberton, Zia Moinuddin, Angela Summers, David van Dellen, Titus Augustine
In sepsis, trauma and major surgery, where an explicit physiological insult leads to a significant systemic inflammatory response, the acute evolution of biomarkers have been delineated. In these settings, Interleukin (IL) -6 and TNF-α are often the first pro-inflammatory markers to rise, stimulating production of acute phase proteins followed by peaks in anti-inflammatory markers. Patients undergoing SPKT as a result of diabetic complications already have an inflammatory phenotype as a result of uraemia and glycaemia...
February 8, 2018: Cytokine
https://www.readbyqxmd.com/read/29415882/swiprosin-1-deficiency-impairs-macrophage-immune-response-of-septic-mice
#13
Su Zhang, Ye Tu, Yi-Ming Sun, Ya Li, Rong-Mei Wang, Yongbing Cao, Ling Li, Li-Chao Zhang, Zhi-Bin Wang
Despite the fact that many therapeutic strategies have been adopted to delay the development of sepsis, sepsis remains one of the leading causes of death in noncoronary intensive care units. Recently, sepsis-3 was defined as life-threatening organ dysfunction due to a dysregulated host response to infection. Here, we report that swiprosin-1 (also known as EFhd2) plays an important role in the macrophage immune response to LPS-induced or cecal ligation and puncture-induced (CLP-induced) sepsis in mice. Swiprosin-1 depletion causes higher mortality, more severe organ dysfunction, restrained macrophage recruitment in the lung and kidney, and attenuated inflammatory cytokine production (including IL-1β, IL-6, TNF-α, IL-10, and IFN-γ)...
February 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29414324/adar1-prevents-small-intestinal-injury-from-inflammation-in-a-murine-model-of-sepsis
#14
Shanshou Liu, Jiangang Xie, Bin Zhao, Xiaomin Hu, Xiao Li, Bin Zhang, Xianqi Wang, Yanjun Wang, Jinquan Jiang, Wen Yin, Junjie Li
Adenosine deaminase acting on RNA 1 (ADAR1), a double-stranded RNA-editing enzyme that converts adenosine (A) to inosine (I), has been identified as a modulator of immune responses. However, the role of ADAR1 in small intestinal homeostasis during sepsis remains unclear. In this study, we examined the role of ADAR1 on intestinal inflammation in a murine model of sepsis. We found that ADAR1 was highly expressed in "septic" macrophages and small intestinal tissue of septic mice. Deletion of ADAR1 in "septic" macrophages led to rapid apoptosis...
February 6, 2018: Cytokine
https://www.readbyqxmd.com/read/29402363/-effect-of-neuregulin-1-on-heart-function-and-inflammatory-mediators-in-rats-with-sepsis
#15
Qin Zhou, Long Wang, Xi Wang, Qiong Xiong, Yanian Wei, Song Dang, Liang Zhong
OBJECTIVE: To explore the protective effect of neuregulin-1 (NRG-1) on heart function and myocardium in rats with sepsis and its mechanism. METHODS: Healthy male Sprague-Dawly (SD) rats were divided into three groups according to random number table method, with 6 rats in each group. Sepsis model was established by cecal ligation and puncture (CLP group); rats in sham operation group (sham group) underwent the same procedure except ligation. Rats in NRG-1 pre-treatment group (NRG group) were intravenously injected with recombinant human NGR-1 (rhNRG-1) at the dose of 10 μg/kg through tail vein; rats in CLP group and sham group were treated with the same amount of saline...
February 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29401625/novel-half-life-extended-anti-mif-nanobodies-protect-against-endotoxic-shock
#16
Amanda Sparkes, Patrick De Baetselier, Lea Brys, Inês Cabrito, Yann G-J Sterckx, Steve Schoonooghe, Serge Muyldermans, Geert Raes, Richard Bucala, Peter Vanlandschoot, Jo A Van Ginderachter, Benoît Stijlemans
Sepsis-leading to septic shock-is the leading cause of death in intensive care units. The systemic inflammatory response to infection, which is initiated by activated myeloid cells, plays a key role in the lethal outcome. Macrophage migration inhibitory factor (MIF) is an upstream immunoregulatory mediator, released by myeloid cells, that underlies a common genetic susceptibility to different infections and septic shock. Accordingly, strategies that are aimed at inhibiting the action of MIF have therapeutic potential...
January 25, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29397306/anti-inflammatory-roles-of-mesenchymal-stromal-cells-during-acute-streptococcus-pneumoniae-pulmonary-infection-in-mice
#17
Takahiro Asami, Makoto Ishii, Ho Namkoong, Kazuma Yagi, Sadatomo Tasaka, Takanori Asakura, Shoji Suzuki, Tetsuro Kamo, Satoshi Okamori, Hirofumi Kamata, Haiyue Zhang, Ahmed E Hegab, Naoki Hasegawa, Tomoko Betsuyaku
BACKGROUND: Pneumonia is the fourth leading cause of death worldwide, and Streptococcus pneumoniae is the most commonly associated pathogen. Increasing evidence suggests that mesenchymal stromal cells (MSCs) have anti-inflammatory roles during innate immune responses such as sepsis. However, little is known about the effect of MSCs on pneumococcal pneumonia. METHODS: Bone marrow-derived macrophages (BMDMs) were stimulated with various ligands in the presence or absence of MSC-conditioned medium...
January 31, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29393983/a-novel-role-for-coinhibitory-receptors-checkpoint-proteins-in-the-immunopathology-of-sepsis
#18
REVIEW
Eleanor A Fallon, Bethany M Biron-Girard, Chun-Shiang Chung, Joanne Lomas-Neira, Daithi S Heffernan, Sean F Monaghan, Alfred Ayala
Coinhibitory molecules, such as PD-1, CTLA-4, 2B4, and BTLA, are an important new family of mediators in the pathophysiology of severe bacterial and/or fungal infection, as well as the combined insults of shock and sepsis. Further, the expression of these molecules may serve as indicators of the immune status of the septic individual. Using PD-1:PD-L as an example, we discuss in this review how such checkpoint molecules may affect the host response to infection by mediating the balance between effective immune defense and immune-mediated tissue injury...
February 2, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29393431/knockout-of-toll-like-receptor-4-improves-survival-and-cardiac-function-in-a-murine-model-of-severe-sepsis
#19
Dan Zhou, Yun Zhu, Min-Zhi Ouyang, Ming Zhang, Kui Tang, Cheng-Cheng Niu, Ling Li
Toll-like receptor 4 (TLR4) is a transmembrane pattern‑recognition receptor expressed in immune cells and the heart. Activation of TLR4 signaling during sepsis results in the release of cardiac depression mediators that may impair heart function. The present study aimed to determine whether TLR4 contributes to development of severe sepsis‑induced myocardial dysfunction. A cecum ligation and puncture (CLP) procedure was employed to establish severe sepsis models. Wild type (WT) and TLR4 knock‑out (TLR4‑KO) mice were divided into four groups: WT‑sham, TLR4‑KO‑sham, WT‑CLP, and TLR4‑KO‑CLP...
January 25, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29393221/the-synergy-of-endotoxin-and-1%C3%A2-3-%C3%AE-d-glucan-from-gut-translocation-worsens-sepsis-severity-in-a-lupus-model-of-fc-gamma-receptor-iib-deficient-mice
#20
Jiraphorn Issara-Amphorn, Saowapha Surawut, Navaporn Worasilchai, Arthid Thim-Uam, Malcolm Finkelman, Ariya Chindamporn, Tanapat Palaga, Nattiya Hirankarn, Prapaporn Pisitkun, Asada Leelahavanichkul
We investigated the influence of spontaneous gut leakage upon polymicrobial sepsis in a lupus model with Fc gamma receptor IIb-deficient (FcGRIIb-/-) mice aged 8 and 40 weeks, as representing asymptomatic and symptomatic lupus, respectively. Spontaneous gut leakage, determined by (i) the presence of FITC-dextran, (ii) elevated serum endotoxin, and (iii) elevated serum (1→3)-β-D-glucan (BG), was demonstrated in symptomatic lupus but not in the asymptomatic group. In parallel, spontaneous gut leakage, detected by elevated serum BG without fungal infection, was demonstrated in patients with active lupus nephritis...
January 31, 2018: Journal of Innate Immunity
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