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sepsis macrophage

Zhixiang Xie, Zhuangbo Guo, Jianfeng Liu
BACKGROUND Whey acidic protein/four-disulfide core domain 21 (Wfdc21), also known as Lnc-DC, it has been reported to be correlated with immune response. However, the role of Wfdc21 in the pathogenesis of sepsis is still unknown. In the present study, we aimed to investigate the role of Wfdc21 in the pathogenesis of sepsis. MATERIAL AND METHODS The cecal ligation and puncture (CLP)-induced sepsis model was established in Balb/c mice. Animals were euthanized 4, 8, 16, or 24 h after CLP. The glycogen distribution in the kidney and liver was checked by Periodic acid-Schiff (PAS) staining...
June 14, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Laurence Black, Jeremie M Lever, Amie M Traylor, Bo Chen, Zhengqin Yang, Stephanie Esman, Yanlin Jiang, Gary Cutter, Ravindra Boddu, James George, Anupam Agarwal
Chronic kidney disease (CKD) is a condition with significant morbidity and mortality that affects 15% of adults in the United States. One cause of CKD is acute kidney injury (AKI), which commonly occurs secondary to sepsis, ischemic events, and drug-induced nephrotoxicity. Unilateral ischemia-reperfusion injury (UIRI) without contralateral nephrectomy (CLN) and repeated low dose cisplatin (RLDC) models of AKI to CKD demonstrate responses characteristic of the transition; however, previous studies have not effectively compared the pathogenesis...
June 13, 2018: American Journal of Physiology. Renal Physiology
Xuyun Gu, Chen Wei, Xishan Zhu, Feiping Lu, Bo Sheng, Xuefeng Zang
Sepsis with severe systemic inflammation remains a great challenge for the intensive care unit in clinics. Although biomarkers have been identified to diagnose, monitor and predict these syndromes, novel therapeutic approaches are required for the amelioration of symptoms of sepsis and septic shock. The present study demonstrated that interleukin (IL)-31 was able reduce the mortality rate of lipopolysaccharide (LPS)-induced sepsis with the reduction of inflammatory cytokines in the sera. IL-31 also inhibited IL-1β production in the peritoneal lavage fluid in LPS-induced or cecal ligation and puncture-induced sepsis...
July 2018: Experimental and Therapeutic Medicine
Rima Tapader, Dipro Bose, Pujarini Dutta, Santasabuj Das, Amit Pal
SslE (YghJ), a cell surface associated and secreted lipoprotein was identified as a potential vaccine candidate for extraintestinal pathogenic E. coli providing nearly complete protection from sepsis in a mouse model. We earlier found that SslE from neonatal septicemic E. coli could trigger the secretion of various proinflammatory cytokines in murine macrophages, the signaling pathway of which is still obscure. In this study, we showed that SslE specifically binds to TLR2/TLR1 heterodimer and recruits downstream adaptors MyD88, TIRAP and TRAF6...
June 11, 2018: Infection and Immunity
Zakia Sefsafi, Brahim El Hasbaoui, Amina Kili, Aomar Agadr, Mohammed Khattab
Macrophage activation syndrome (MAS) is a severe and potentially fatal life-threatening condition associated with excessive activation and expansion of T cells with macrophages and a high expression of cytokines, resulting in an uncontrolled inflammatory response, with high levels of macrophage colony-stimulating factor and causing multiorgan damage. This syndrome is classified into primary (genetic/familial) or secondary forms to several etiologies, such as infections, neoplasias mainly hemopathies or autoimmune diseases...
2018: Pan African Medical Journal
Balázs Csóka, Zoltán H Németh, Ildikó Szabó, Daryl L Davies, Zoltán V Varga, János Pálóczi, Simonetta Falzoni, Francesco Di Virgilio, Rieko Muramatsu, Toshihide Yamashita, Pál Pacher, György Haskó
The macrophage is a major phagocytic cell type, and its impaired function is a primary cause of immune paralysis, organ injury, and death in sepsis. An incomplete understanding of the endogenous molecules that regulate macrophage bactericidal activity is a major barrier for developing effective therapies for sepsis. Using an in vitro killing assay, we report here that the endogenous purine ATP augments the killing of sepsis-causing bacteria by macrophages through P2X4 receptors (P2X4Rs). Using newly developed transgenic mice expressing a bioluminescent ATP probe on the cell surface, we found that extracellular ATP levels increase during sepsis, indicating that ATP may contribute to bacterial killing in vivo...
June 7, 2018: JCI Insight
Xiaozhi Bai, Ting He, Yang Liu, Julei Zhang, Xiaoqiang Li, Jihong Shi, Kejia Wang, Fu Han, Wei Zhang, Yijie Zhang, Weixia Cai, Dahai Hu
SIRT1 is reported to participate in macrophage differentiation and affect sepsis, and Notch signaling is widely reported to influence inflammation and macrophage activation. However, the specific mechanisms through which SIRT1 regulates sepsis and the relationship between SIRT1 and Notch signaling remain poorly elucidated. In this study, we found that SIRT1 levels were decreased in sepsis both in vitro and in vivo and that SIRT1 regulation of Notch signaling affected inflammation. In lipopolysaccharide (LPS)-induced sepsis, the levels of Notch signaling molecules, including Notch1, Notch2, Hes1, and intracellular domain of Notch (NICD), were increased...
2018: Frontiers in Immunology
Dustin R Middleton, Amy V Paschall, Jeremy A Duke, Fikri Y Avci
Despite a century of investigation, Streptococcus pneumoniae ( Spn ) remains a major human pathogen, causing a number of diseases such as pneumonia, meningitis, and otitis media. Like many encapsulated pathogens, the capsular polysaccharide (CPS) of Spn is a critical component for colonization and virulence in mammalian hosts. This study aimed to evaluate the protective role of a glycoside hydrolase, Pn3Pase, targeting the CPS of type 3 Spn , which is one of the most virulent serotypes. We have assessed the ability of Pn3Pase to degrade the capsule on a live type 3 strain...
June 4, 2018: Infection and Immunity
Annette Wegner, Dragan Pavlovic, Sebastian Haußmann-Vopel, Christian Lehmann
It has been observed, that patients who were treated medically for dyslipoproteinemia had a potentially lower risk of complications during infection and sepsis, regarding both morbidity and mortality. Aim of this study in experimental sepsis was to elucidate the impact of lipid metabolism modulation by simvastatin, HDL, or bezafibrate, respectively, on the intestinal microcirculation which plays a crucial role in the development of multiple organ failure in sepsis. Experimental sepsis was induced in Lewis rats by intravenous lipopolysaccharide (LPS) administration...
May 31, 2018: Microvascular Research
Xiang Si, Daiyin Cao, Juan Chen, Yao Nie, Zhiyi Jiang, Min-Ying Chen, Jian-Feng Wu, Xiang-Dong Guan
Autophagy, part of the innate immune defense mechanisms, is activated during the initial phase of septic insult. Previous studies indicated that micro (mi)RNAs are additionally involved in the host response to sepsis; however, the association between miRNAs and autophagy during this process is not fully understood. To study the role of miRNA (miR)‑23a in autophagy initiated by sepsis, macrophages treated with lipopolysaccharides, in addition to blood samples from patients, were evaluated for miR‑23a expression levels...
May 29, 2018: Molecular Medicine Reports
Jia-Yih Feng, Wei-Juin Su, Sheng-Wei Pan, Yi-Chen Yeh, Yung-Yang Lin, Nien-Jung Chen
Triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory responses and is upregulated during sepsis and pulmonary infection. The association between serum soluble TREM-1 (sTREM-1) level and pulmonary tuberculosis (PTB) disease deserves investigation. In the present study, patients with PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects were prospectively enrolled and serum levels of sTREM-1, sTREM-2, and C-reactive protein (CRP) were measured. We correlated serum biomarkers and clinical presentations and treatment outcomes of PTB cases...
May 29, 2018: Scientific Reports
Tobias Zrzavy, Romana Höftberger, Thomas Berger, Helmut Rauschka, Oleg Butovsky, Howard Weiner, Hans Lassmann
AIMS: Experimental data suggest that systemic immune activation may create a pro-inflammatory environment with microglia activation in the central nervous system in the absence of overt inflammation, which in turn may be deleterious in conditions of neurodegenerative disease. The extent to which this is relevant for the human brain is unknown. The central aim of this study is to provide an in-depth characterization of the microglia and macrophage response to systemic inflammation. METHODS: We used recently described markers to characterize the origin and functional states of microglia/macrophages in white and grey matter in patients who died under septic conditions and compared it to those patients without systemic inflammation...
May 27, 2018: Neuropathology and Applied Neurobiology
Guangliang Hong, Dong Zheng, Lulu Zhang, Rui Ni, Grace Wang, Guo-Chang Fan, Zhongqiu Lu, Tianqing Peng
AIMS: Sepsis-caused multiple organ failure remains the major cause of morbidity and mortality in intensive care units. Nicotinamide riboside (NR) is a precursor of nicotinamide adenine dinucleotide (NAD+ ), which is important in regulating oxidative stress. This study investigated whether administration of NR prevented oxidative stress and organ injury in sepsis. METHODS: Mouse sepsis models were induced by injection of lipopolysaccharides (LPS) or feces-injection-in-peritoneum...
May 24, 2018: Free Radical Biology & Medicine
Qinlan Wang, Chunmei Wang, Nan Li, Xingguang Liu, Wenhui Ren, Qingqing Wang, Xuetao Cao
Structural maintenance of chromosome (Smc) protein complex (condensin) plays a central role in organizing and compacting chromosomes, which determines DNA-binding activity and gene expression; however, the role of condensin Smc in innate immunity and inflammation remains largely unknown. Through a high-throughput screening of the epigenetic modifiers, we identified Smc4, a core subunit of condensin, to potentially promote inflammatory innate immune response. Knockdown or deficiency of Smc4 inhibited TLR- or virus-triggered production of proinflammatory cytokines IL-6, TNF-α and IFN-β in macrophages...
May 24, 2018: Journal of Autoimmunity
Fang Li, Fangfang Lang, Yidan Wang, Chunxiao Zhai, Chuanbei Zhang, Liping Zhang, Enkui Hao
Cyanidin, an anthocyanin pigment, demonstrates anti-oxidant and anti-inflammatory properties. Here, we examined the mechanistic role of cyanidin in endotoxin induced myocardial injury in inflammation and oxidative stress. In lipopolysaccharide (LPS) induced myocardial injury model, cyanidin ameliorated cardiac injury (Lactate dehydrogenase or LDH, Creatine Kinase or CK, cardiac troponin I or cTnI and cardiac myosin light chains 1 or cMLC1), cell death (caspase 3 activity and PARP activity), and improved cardiac function (ejection fraction or EF and end diastolic left ventricular inner dimension or LVID)...
May 24, 2018: Food and Chemical Toxicology
Mei Kuang, Yanyan Cen, Rongxin Qin, Shenglan Shang, Zhaoxia Zhai, Chao Liu, Xichun Pan, Hong Zhou
BACKGROUND/AIMS: Lipopolysaccharide (LPS) plays a critical role in excessive inflammatory cytokine production during sepsis. Previously, artesunate (AS) was reported to protect septic mice by reducing LPS-induced pro-inflammatory cytokine release. In the present study, the possible mechanism of the anti-inflammatory effect of AS was further investigated. METHODS: An enzyme-linked immunosorbent assay was used to detect TNF-α and IL-6 release from macrophages. Specific small interfering RNAs (siRNAs) were used to knockdown the mRNA expression of target genes...
May 22, 2018: Cellular Physiology and Biochemistry
Xi-Ling Wang, Li-Long Pan, Fen Long, Wei-Jun Wu, Di Yan, Peng Xu, Si-Yu Liu, Ming Qin, Wan-Wan Jia, Xin-Hua Liu, Yi Zhun Zu
BACKGROUND/AIMS: Sepsis is a severe and complicated syndrome that is characterized by dysregulation of host inflammatory responses and organ failure. Cystathionine-γ-lyase (CSE)/ hydrogen sulfide (H2S) has potential anti-inflammatory activities in a variety of inflammatory diseases. NADPH oxidase 4 (Nox4), a member of the NADPH oxidases, is the major source of reactive oxygen species (ROS) and its expression is increased in sepsis, but its function in CSE-mediated anti-inflammatory activities remains unknown...
May 22, 2018: Cellular Physiology and Biochemistry
Jie Zhen, Wei Chen
This study aims to explore the roles of miR-142/PD-L1 axis in cecal ligation and puncture (CLP)-induced inflammation and the survival in septic mice. Here, miR-142 was found to be decreased in sepsis patients. And miR-142 was decreased but PD-L1 was increased in CLP-treated mice macrophages in a time-dependent manner. Mechanistically, miR-142/PD-L1 regulatory axis was identified in macrophages. Pre-injection of miR-142 agomir following CLP treatment attenuated CLP-induced inflammation, characterized as the downregulation of IL-2 and TNF-α secretion, but this effect could not be ameliorated by post-injection of miR-142 agomir after CLP treatment...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Linsong Chen, Yanfeng Zhao, Dengming Lai, Peng Zhang, Yang Yang, Yuehua Li, Ke Fei, Gening Jiang, Jie Fan
In response to infection, polymorphonuclear neutrophils (PMN) are recruited in the infectious sites, and employ three major strategies to fight against the microbes including phagocytosis, degranulation, and neutrophil extracellular traps (NETs). NETs are a meshwork of chromatin fibers mixed with granule-derived antimicrobial peptides and enzymes, which trap and kill the bacteria extracellularly. In this study, by using a mouse sepsis model, we identified a novel mechanism by which NETs induce macrophage (Mϕ) pyroptosis, a caspase-1-dependent regulated cell death...
May 22, 2018: Cell Death & Disease
Hye-Eun Choi, Hyun Jeong Kwak, Seul Ki Kim, Hyae Gyeong Cheon
Foenumoside B (FSB), a bioactive component isolated from the Lysimachia foenum-graecum extract (LFE), has been shown to possess anti-inflammatory effects, but the underlying molecular mechanisms involved have not been elucidated. Accordingly, the authors investigated the mechanisms responsible for the anti-inflammatory effects of FSB in murine macrophages activated by LPS. FSB suppressed the LPS-induced expressions of iNOS and COX-2 at protein and mRNA levels and consequently decreased NO and PGE2 production in RAW264...
May 18, 2018: European Journal of Pharmacology
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