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https://www.readbyqxmd.com/read/29455288/mycophenolate-mofetil-protects-septic-mice-via-the-dual-inhibition-of-inflammatory-cytokines-and-pd-1
#1
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/29449632/inducible-nitric-oxide-synthase-during-the-late-phase-of-sepsis-is-associated-with-hypothermia-and-immune-cell-migration
#2
Yudai Takatani, Kenji Ono, Hiromi Suzuki, Masato Inaba, Makoto Sawada, Naoyuki Matsuda
Hypothermia is a significant sign of sepsis, which is associated with poor prognosis, but few mechanisms underlying the regulation of hypothermia are known. Inducible nitric oxide synthase (iNOS) is a key inflammatory mediator of sepsis. However, the therapeutic benefit of iNOS inhibition in sepsis is still controversial, and requires elucidation in an accurate model system. In this study, wild-type (WT) mice showed temperature drops in a biphasic manner at the early and late phase of sepsis, and all mice died within 48 h of sepsis...
February 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29434744/interleukin-1-receptor-associated-kinase-3-downregulation-in-peripheral-blood-mononuclear-cells-attenuates-immunosuppression-in-sepsis
#3
Qin Xia, Yupin Zhou, Xi Wang, Shukun Fu
Sepsis is the leading cause of mortality in intensive care units due to complex inflammatory immune responses and immunosuppression. Recent studies have indicated that the negative regulator of toll like receptors, interleukin-1 receptor-associated kinase 3 (IRAK-3/IRAK-M), serves an important role in immunosuppression during sepsis. In the current study, a cecal ligation puncture model was established in mice using lipopolysaccharide secondary challenge to simulate immunosuppression in sepsis. Peripheral blood mononuclear cells (PBMCs) from this model were then used to evaluate the expression and function of IRAK-M...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434211/a-cold-inducible-rna-binding-protein-cirp-derived-peptide-attenuates-inflammation-and-organ-injury-in-septic-mice
#4
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
#5
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/29431198/metabolomic-analysis-for-the-protective-effects-of-mangiferin-on-sepsis-induced-lung-injury-in-mice
#6
Yiling Wang, Yang Liu, Qiqi Cao, Xuan Shi, Hongtao Lu, Songyan Gao, Rui Yang
This study is aimed to investigate the efficacy of mangiferin, including its known antioxidant and anti-inflammatory effects on sepsis-induced lung injury induced by a classical cecal ligation and puncture (CLP) models in mouse using a metabolomics approach. Generally a total of twenty-four mice were randomly divided into four groups: sham group was given saline before sham operation. CLP group was received CLP operation only. HMF and LMF groups were given mangiferin treatment of high dose and low dose of mangiferin respectively before CLP operation...
February 12, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29428597/possible-involvement-of-tetrahydrobiopterin-in-the-disturbance-of-redox-homeostasis-in-sepsis-induced-brain-dysfunction
#7
Maha Gamal, Jackline Moawad, Laila Rashid, Mary Attia Morcos, Nivin Sharawy
BACKGROUND AND AIM: Tetrahydrobiopterin (BH4) is an essential co-factor that regulates nitric oxide (NO) and reactive oxygen species (ROS) production by nitric oxidesynthases (NOS). In this study, we evaluated the effects of sepsis on BH 4 level and redox status in the brain by using the rat model of sepsis- induced by cecal ligation and puncture (CLP) and examined whether BH4 and/or acetyl-L-carnitine(ALC) could prevent the neuronal apoptosis and neurological changes induced by sepsis...
February 8, 2018: Brain Research
https://www.readbyqxmd.com/read/29424793/regulators-of-intestinal-epithelial-migration-in-sepsis
#8
Mei Meng, Nathan J Klingensmith, Zhe Liang, John D Lyons, Katherine T Fay, Ching-Wen Chen, Mandy L Ford, Craig M Coopersmith
The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit...
February 8, 2018: Shock
https://www.readbyqxmd.com/read/29415882/swiprosin-1-deficiency-impairs-macrophage-immune-response-of-septic-mice
#9
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/29409946/fabp4-inhibitors-suppress-inflammation-and-oxidative-stress-in-murine-and-cell-models-of-acute-lung-injury
#10
Yuanqi Gong, Zhihong Yu, Yi Gao, Linlin Deng, Meng Wang, Yu Chen, Jingying Li, Bin Cheng
Acute lung injury (ALI) is a severe disease with high morbidity and mortality, and is characterized by devastating inflammation of the lung and increased production of reactive oxygen species (ROS). Recent studies have indicated that fatty acid binding protein (FABP4) is important in the regulation of inflammation. However, the role of FABP4 in sepsis-related ALI, and the specific mechanism of action have not been examined. In vitro, the exposure of human alveolar epithelial A549 cells to lipopolysaccharide (LPS) and recombinant FABP4 (hrFABP4) resulted in the production of pro-inflammatory cytokines, inflammatory cytokines, and ROS, while these changes were ameliorated by pretreatment with the FABP4 inhibitor BMS309403 and FABP4 siRNA...
February 1, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29406423/activator-protein-1-decoy-oligodeoxynucleotide-transfection-is-beneficial-in-reducing-organ-injury-and-mortality-in-septic-mice
#11
Takahiro Imaizumi, Naoyuki Matsuda, Kengo Tomita, Sailesh Palikhe, Wakana Ohashi, Kohshi Hattori, Yuichi Hattori
OBJECTIVES: Inflammation and apoptosis are decisive mechanisms for the development of end-organ injury in sepsis. Activator protein-1 may play a key role in regulating expression of harmful genes responsible for the pathophysiology of septic end-organ injury along with the major transcription factor nuclear factor-κB. We investigated whether in vivo introduction of circular dumbbell activator protein-1 decoy oligodeoxynucleotides can provide benefits for reducing septic end-organ injury...
February 5, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29402363/-effect-of-neuregulin-1-on-heart-function-and-inflammatory-mediators-in-rats-with-sepsis
#12
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/29401137/differential-effects-of-selective-and-nonselective-potassium-channel-inhibitors-in-ovine-endotoxemic-shock-macrocirculation-and-in-a-rat-model-of-septic-shock-microcirculation
#13
Michael Hessler, Bernardo B Pinto, Philip-Helge Arnemann, Tim-Gerald Kampmeier, Laura Seidel, Andrea Morelli, Hugo Van Aken, Martin Westphal, Sebastian Rehberg, Christian Ertmer
BACKGROUND: Potassium-(K)-channel inhibitors may increase systemic vascular resistance in vasodilatory shock states. OBJECTIVE: The purpose of the present study was to compare the macro- and microvascular effects of the adenosine triphosphate-sensitive K-channel-(KATP)-inhibitor glipizide and the nonselective K-channel inhibitor tetraethylammonium (TEA) in ovine endotoxemic shock and septic shock in rats. DESIGN: Two randomized, controlled laboratory studies...
February 2, 2018: Shock
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
#14
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
https://www.readbyqxmd.com/read/29384785/interleukin-34-ameliorates-survival-and-bacterial-clearance-in-polymicrobial-sepsis
#15
Xue Lin, Hongchun Luo, Xingxing Yan, Zhixin Song, Xun Gao, Yun Xia, Liping Zhang, Yibing Yin, Ju Cao
OBJECTIVES: Sepsis is a devastating condition with a high mortality rate and limited treatments. Sepsis is characterized by a failed host immune response to contain the infection, resulting in organ dysfunction. Interleukin-34 is new cytokine involved in infection and immunity. Whether interleukin-34 is beneficial or deleterious to sepsis and the underlying mechanisms remains unknown. DESIGN: Prospective randomized animal investigation and in vitro studies. SETTING: Research laboratory at a university hospital...
January 30, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29374076/pad4-deficiency-leads-to-decreased-organ-dysfunction-and-improved-survival-in-a-dual-insult-model-of-hemorrhagic-shock-and-sepsis
#16
Bethany M Biron, Chun-Shiang Chung, Yaping Chen, Zachary Wilson, Eleanor A Fallon, Jonathan S Reichner, Alfred Ayala
Indirect acute respiratory distress syndrome (iARDS) is caused by a nonpulmonary inflammatory process resulting from insults such as nonpulmonary sepsis. Neutrophils are thought to play a significant role in mediating ARDS, with the development of iARDS being characterized by dysregulation and recruitment of activated neutrophils into the lung. Recently, a novel mechanism of microbial killing by neutrophils was identified through the formation of neutrophil extracellular traps (NETs). NETs are composed of large webs of decondensed chromatin released from activated neutrophils into the extracellular space; they are regulated by the enzyme peptidylarginine deiminase 4 (PAD4) through mediation of chromatin decondensation via citrullination of target histones...
January 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29370574/the-protective-effect-of-ticagrelor-on-renal-function-in-a-mouse-model-of-sepsis-induced-acute-kidney-injury
#17
Xiuhua Li, Yusheng Li, Kan Shen, Hongqiang Li, Jianwen Bai
Platelets are traditionally considered to be essential components of primary hemostasis. Recent investigations have revealed that platelets can be activated in patients with sepsis and are implicated in the development of sepsis and sepsis-induced-acute kidney injury (SAKI). In the present study, ticagrelor was used to induce a mouse model of SAKI by cecal ligation and puncture. It was found that ticagrelor could inhibit platelet activity, decrease the levels of interleukin-1β and serum creatinine, reduce infiltration of neutrophils in renal tissue, and attenuate cell apoptosis in the kidney...
January 25, 2018: Platelets
https://www.readbyqxmd.com/read/29369056/prompt-administration-of-antibiotics-and-fluids-in-the-treatment-of-sepsis-a-murine-trial
#18
Anthony J Lewis, John E Griepentrog, Xianghong Zhang, Derek C Angus, Christopher W Seymour, Matthew R Rosengart
OBJECTIVES: Sepsis, the acute organ dysfunction caused by a dysregulated host response to infection, poses a serious public health burden. Current management includes early detection, initiation of antibiotics and fluids, and source control as necessary. Although observational data suggest that delays of even a few hours in the initiation of antibiotics or IV fluids is associated with survival, these findings are controversial. There are no randomized data in humans, and prior animal studies studied time from experimental manipulation, not from the onset of clinical features of sepsis...
January 23, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29365277/interferon-%C3%AE-improves-sepsis-related-alveolar-macrophage-dysfunction-and-post-septic-ards-related-mortality
#19
Takahiro Hiruma, Hitoshi Tsuyuzaki, Kanji Uchida, Bruce C Trapnell, Yoshiro Yamamura, Yoshiomi Kusakabe, Tokie Totsu, Takuji Suzuki, Shigeki Morita, Kent Doi, Eisei Noiri, Kensuke Nakamura, Susumu Nakajima, Naoki Yahagi, Naoto Morimura, Kyungho Chang, Yoshitsugu Yamada
Interferon-β (IFNβ) is reported to improve survival in patients with acute respiratory distress syndrome (ARDS), possibly by preventing sepsis-induced immunosuppression, but its therapeutic nature in ARDS pathogenesis is poorly understood. We investigated the therapeutic effects of IFNβ for post-septic ARDS to better understand its pathogenesis in mice. Post-septic ARDS was reproduced in mice by cecal ligation and puncture to induce sepsis followed 4 days later by intratracheal instillation of Pseudomonas aeruginosa to cause pneumonia with or without subcutaneous administration of IFNβ 1 day earlier...
January 24, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29348412/influence-of-autophagy-on-acute-kidney-injury-in-a-murine-cecal-ligation-and-puncture-sepsis-model
#20
Satoshi Sunahara, Eizo Watanabe, Masahiko Hatano, Paul E Swanson, Takehiko Oami, Lisa Fujimura, Youichi Teratake, Takashi Shimazui, Chiwei Lee, Shigeto Oda
The role of autophagy in the maintenance of renal homeostasis during sepsis is not well understood. We therefore aimed to determine the influence of autophagy on kidney during sepsis using a murine sepsis model, i.e. cecal ligation and puncture (CLP). In CLP treated animals, the number of autolysosomes observed by electron microscopy increased over time. The number of autophagosomes in CLP animals decreased relative sham operated controls at 24 hrs after CLP, indicating that autophagy flux is already diminishing by that time...
January 18, 2018: Scientific Reports
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