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https://www.readbyqxmd.com/read/29924419/induction-of-endoplasmic-reticulum-stress-under-endotoxin-tolerance-increases-inflammatory-responses-and-decreases-pseudomonas-aeruginosa-pneumonia
#1
Sena Kim, Yeonsoo Joe, Se-Ung Park, Sun Oh Jeong, Jin-Kyung Kim, Seong Hoon Park, Hyun-Ock Pae, Young-Joon Surh, Jaekyoon Shin, Hun Taeg Chung
Endotoxin tolerance develops in the late phase of sepsis to protect cells from an early hyperinflammatory response. Nonetheless, because it induces an immunosuppressive environment, patients with sepsis in its late phase are affected by secondary infections, particularly bacterial pneumonia. Here, we showed that induction of endoplasmic reticulum (ER) stress leads to activation of glycogen synthase kinase 3β (GSK-3β) and X-box-binding protein 1 (XBP-1) in an inositol-requiring enzyme 1α (IRE1α)-mediated manner, which in turn restores the inflammatory response in endotoxin-tolerant macrophages...
June 20, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29922941/cardioprotective-and-functional-effects-of-levosimendan-and-milrinone-in-mice-with-cecal-ligation-and-puncture-induced-sepsis
#2
Shigeyuki Yamashita, Tokiko Suzuki, Keisuke Iguchi, Takuya Sakamoto, Kengo Tomita, Hiroki Yokoo, Mari Sakai, Hiroki Misawa, Kohshi Hattori, Toshi Nagata, Yasuhide Watanabe, Naoyuki Matsuda, Naoki Yoshimura, Yuichi Hattori
Levosimendan and milrinone may be used in place of dobutamine to increase cardiac output in septic patients with a low cardiac output due to impaired cardiac function. The effects of the two inotropic agents on cardiac inflammation and left ventricular (LV) performance were examined in mice with cecal ligation and puncture (CLP)-induced sepsis. CLP mice displayed significant cardiac inflammation, as indicated by highly increased pro-inflammatory cytokines and neutrophil infiltration in myocardial tissues. When continuously given, levosimendan prevented but milrinone exaggerated cardiac inflammation, but they significantly reduced the elevations in plasma cardiac troponin-I and heart-type fatty acid-binding protein, clinical markers of cardiac injury...
June 20, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29922426/metformin-attenuated-sepsis-induced-oxidative-damages-a-novel-role-for-metformin
#3
Hamed Ghavimi, Sasan Sheidaei, Haleh Vaez, Elmira Zolali, Parina Asgharian, Hadi Hamishehkar
Objectives: Sepsis can result in severe organ injury by provoking inflammatory cascades and oxidative stress. Several studies are currently underway to find a drug with anti-inflammatory effects to prevent mortality and morbidity during sepsis. The present study was undertaken to assess the effects of metformin on oxidative stress and antioxidant status in sepsis induced by the Cecal Ligation and Puncture (CLP) method. Materials and Methods: Male Wistar rats were divided into 4 groups (n=10): sham, CLP, and 50 and 100 mg/kg metformin-treated CLP groups...
May 2018: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29914696/role-of-complement-c5a-and-histones-in-septic-cardiomyopathy
#4
Fatemeh Fattahi, Lynn M Frydrych, Guowu Bian, Miriam Kalbitz, Todd J Herron, Elizabeth A Malan, Matthew J Delano, Peter A Ward
Polymicrobial sepsis (after cecal ligation and puncture, CLP) causes robust complement activation with release of C5a. Many adverse events develop thereafter and will be discussed in this review article. Activation of complement system results in generation of C5a which interacts with its receptors (C5aR1, C5aR2). This leads to a series of harmful events, some of which are connected to the cardiomyopathy of sepsis, resulting in defective action potentials in cardiomyocytes (CMs), activation of the NLRP3 inflammasome in CMs and the appearance of extracellular histones, likely arising from activated neutrophils which form neutrophil extracellular traps (NETs)...
June 15, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29910685/activation-of-central-alpha-7-nicotinic-acetylcholine-receptor-reverses-suppressed-immune-function-of-t-lymphocytes-and-protects-against-sepsis-lethality
#5
Chao Ren, Xiu-Hua Li, Shi-Bin Wang, Li-Xue Wang, Ning Dong, Yao Wu, Yong-Ming Yao
Sepsis remains the leading cause of high mortality and huge financial burden in intensive care units (ICU), but with scarce effective treatments due to refractory multiple organ dysfunction and persistent immunosuppression. Treatments that aim at modulating immune function and attenuating multiple organ injury will certainly benefit septic cases. Alpha 7 nicotinic acetylcholine receptor (α7nAchR) has been reported with potent immunomodulatory properties in various diseases as the essential mediator of the cholinergic anti-inflammatory pathway (CAP)...
2018: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29900929/whey-acidic-protein-four-disulfide-core-domain-21-regulate-sepsis-pathogenesis-in-a-mouse-model-and-a-macrophage-cell-line-via-the-stat3-toll-like-receptor-4-tlr4-signaling-pathway
#6
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
https://www.readbyqxmd.com/read/29896237/effect-of-interleukin-31-on-septic-shock-through-regulating-inflammasomes-and-interleukin-1%C3%AE
#7
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
https://www.readbyqxmd.com/read/29889817/alpha-1-adrenergic-receptor-agonist-phenylephrine-inhibits-sepsis-induced-cardiomyocyte-apoptosis-and-cardiac-dysfunction-via-activating-erk1-2-signal-pathaway
#8
Hongmei Li, Yun Xing, Duomeng Yang, Xiangxu Tang, Daxiang Lu, Huadong Wang
It was demonstrated that α1 adrenergic receptor (α1-AR) activation by phenylephrine (PE) attenuated cardiac dysfunction in lipopolysaccharide (LPS) - challenged mice. However, it is unclear whether PE suppresses sepsis-induced cardiomyocyte apoptosis. Here, we investigated the effects of PE on cardiomyocyte apoptosis in LPS-treated adult rat ventricular myocytes (ARVMs) and septic rats induced by cecal ligation and puncture. Cardiomyocyte apoptosis and caspase activity were detected by TUNEL and spectrophotometrical assay, respectively...
June 8, 2018: Shock
https://www.readbyqxmd.com/read/29889816/murine-pancreatic-cancer-alters-t-cell-activation-and-apoptosis-and-worsens-survival-after-cecal-ligation-and-puncture
#9
John D Lyons, Ching-Wen Chen, Zhe Liang, Wenxiao Zhang, Deena B Chihade, Eileen M Burd, Alton B Farris, Mandy L Ford, Craig Coopersmith
Patients with cancer who develop sepsis have a markedly higher mortality than patients who were healthy prior to the onset of sepsis. Potential mechanisms underlying this difference have previously been examined in two preclinical models of cancer followed by sepsis. Both pancreatic cancer/pneumonia and lung cancer/cecal ligation and puncture (CLP) increase murine mortality, associated with alterations in lymphocyte apoptosis and intestinal integrity. However, pancreatic cancer/pneumonia decreases lymphocyte apoptosis and increases gut apoptosis while lung cancer/CLP increases lymphocyte apoptosis and decreases intestinal proliferation...
June 8, 2018: Shock
https://www.readbyqxmd.com/read/29877959/premise-for-standardized-sepsis-models
#10
Daniel G Remick, Alfred Ayala, Irshad Chaudry, Craig M Coopersmith, Clifford Deutschman, Judith Hellman, Lyle Moldawer, Marcin Osuchowski
Sepsis morbidity and mortality exacts a toll on patients and contributes significantly to healthcare costs. Preclinical models of sepsis have been used to study disease pathogenesis and test new therapies, but divergent outcomes have been observed with the same treatment even when using the same sepsis model. Other disorders such as diabetes, cancer, malaria, obesity and cardiovascular diseases have used standardized, preclinical models that allow laboratories to compare results. Standardized models accelerate the pace of research and such models have been used to test new therapies or changes in treatment guidelines...
June 5, 2018: Shock
https://www.readbyqxmd.com/read/29864919/taurine-enhances-the-protective-effect-of-dexmedetomidine-on-sepsis-induced-acute-lung-injury-via-balancing-the-immunological-system
#11
Wei Zhao, Ling Jia, Hui-Jing Yang, Xiang Xue, Wei-Xiao Xu, Jian-Qin Cai, Rui-Juan Guo, Chang-Chun Cao
Sepsis, an overwhelming systemic inflammatory disease, is the leading cause of acute lung injury (ALI). Despite plenty of researches have been done, effective drugs treating septic ALI are still eagerly needed in the clinic. Dexmedetomidine (Dex), a potent alpha-2 adrenoreceptor agonist, has been reported to possess antioxidant, anti-apoptosis and anti-inflammatory abilities. Taurine, a kind of intracellular free amino acid, has been used to treat various diseases. This study aimed to explore the combination effect of Dex and Taurine on septic ALI and the underlying mechanism in vivo...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29847187/toll-like-receptors-2-3-4-and-7-expression-patterns-in-the-liver-of-a-clp-induced-sepsis-mouse-model
#12
Chrysostomos V Aravanis, Alkistis Kapelouzou, Stylianos Vagios, Diamantis I Tsilimigras, Michalis Katsimpoulas, Demetrios Moris, Theano D Demesticha, Dimitrios Schizas, Alkiviadis Kostakis, Anastasios Machairas, Theodore Liakakos
OBJECTIVE: To investigate the expression of toll-like receptors (TLRs) in the liver of septic mouse model. MATERIALS AND METHODS: For this study seventy-two C57BL/6J mice were utilized. Sepsis was induced by cecal ligation and puncture (CLP) in the mice of the three septic (S) groups (euthanized at 24 hours, 48 hours and 72 hours). Sham (laparotomy)- operated mice constituted the control (C) groups (euthanized at 24, 48 and 72 hours). Blood samples were drawn and liver tissues were extracted and examined histologically...
May 30, 2018: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/29844304/alleviation-of-acute-lung-injury-in-rats-with-sepsis-by-resveratrol-via-the-phosphatidylinositol-3-kinase-nuclear-factor-erythroid-2-related-factor-2-heme-oxygenase-1-pi3k-nrf2-ho-1-pathway
#13
Yu Wang, Xiaofeng Wang, Lichun Zhang, Rong Zhang
BACKGROUND Resveratrol (Res) is a type of polyphenol found in many plants, which can protect important organs from the damage induced by sepsis. However, the exact mechanism of its protective effect has not been established. This study investigated the effect of Res on the PI3K/Nrf2/HO-1 signaling pathway in rats with sepsis-induced acute lung injury (ALI). MATERIAL AND METHODS Male Wistar rats were treated with 30 mg/kg Res by intraperitoneal administration for 1 hour immediately after cecal ligation and puncture...
May 30, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29794022/yap-controls-endothelial-activation-and-vascular-inflammation-through-traf6
#14
Yang Lv, Kyungho Kim, Yue Sheng, Jaehyung Cho, Zhijian Qain, You-Yang Zhao, Gang Hu, Duojia Pan, Asrar B Malik, Guochang Hu
<u>Rationale:</u> Microvascular inflammation and endothelial dysfunction secondary to unchecked activation of endothelium plays a critical role in the pathophysiology of sepsis and organ failure. The intrinsic signaling mechanisms responsible for dampening excessive activation of endothelial cells are not completely understood. <u>Objective:</u> To determine the central role of Yes-associated protein (YAP), the major transcriptional co-activator of the Hippo pathway, in modulating the strength and magnitude of endothelial activation and vascular inflammation...
May 23, 2018: Circulation Research
https://www.readbyqxmd.com/read/29793310/mir-142-inhibits-cecal-ligation-and-puncture-clp-induced-inflammation-via-inhibiting-pd-l1-expression-in-macrophages-and-improves-survival-in-septic-mice
#15
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
https://www.readbyqxmd.com/read/29787988/microrna-30e-promotes-hepatocyte-proliferation-and-inhibits-apoptosis-in-cecal-ligation-and-puncture-induced-sepsis-through-the-jak-stat-signaling-pathway-by-binding-to-fosl2
#16
Lan Ling, Shan-Hong Zhang, Li-Da Zhi, Hong Li, Qian-Kuan Wen, Gang Li, Wen-Jia Zhang
INTRODUCTION: Hepatocyte proliferation and apoptosis are critical cellular behaviors in rat liver as a result of a liver injury. Herein, we performed this study in order to evaluate the role of miR-30e and its target Fos-Related Antigen-2 (FOSL2) in septic rats through the JAK/STAT signaling pathway. METHODS: Rat models of sepsis were induced by cecal ligation and puncture. Enzyme-linked immunosorbent assay (ELISA) was performed to access serum levels of lipopolysaccharide (LPS), inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to confirm the successful establishment of the model...
May 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29787416/cecal-ligation-and-puncture-alters-glucocorticoid-receptor-expression
#17
Mabel N Abraham, Daniela M Jimenez, Tiago D Fernandes, Clifford S Deutschman
OBJECTIVES: Interventional trials on glucocorticoids in sepsis have yielded capricious results. Recent studies have identified multiple glucocorticoid receptor isoforms. The relative abundance of these isoforms in septic patients and following murine cecal ligation and puncture is unknown. The objective of this study is to determine the effects of cecal ligation and puncture on glucocorticoid receptor isoform abundance. DESIGN: Determination of effects of cecal ligation and puncture on glucocorticoid receptor isoform subtype abundance in C57BL/6 mice...
May 21, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29778842/curcumin-attenuates-sepsis-induced-acute-organ-dysfunction-by-preventing-inflammation-and-enhancing-the-suppressive-function-of-tregs
#18
Longwang Chen, Yang Lu, Linjun Zhao, Lili Hu, Qiaomeng Qiu, Zhuoling Zhang, Mengfang Li, Guangliang Hong, Bing Wu, Guangju Zhao, Zhongqiu Lu
Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP)...
May 17, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29765498/edaravone-improves-septic-cardiac-function-by-inducing-an-hif-1-%C3%AE-ho-1-pathway
#19
Chao He, Wei Zhang, Suobei Li, Wei Ruan, Junmei Xu, Feng Xiao
Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29762676/interleukin-38-is-a-protective-cytokine-for-lethal-sepsis
#20
Fang Xu, Shihui Lin, Xingxing Yan, Chuanjiang Wang, Hongmei Tu, Yibing Yin, Ju Cao
Background: IL-38 is the most recently characterized cytokine of the IL-1 family. However, its role in sepsis remains unknown. Methods: Circulating IL-38 was measured in two cohorts of adult and pediatric patients with sepsis. Using two murine models of lipopolysaccharide (LPS)-induced endotoxinemia and cecal ligation and puncture (CLP)-induced sepsis, the effects of IL-38 on survival, inflammation, tissue injury, or bacterial clearance were assessed. Results: Serum IL-38 concentrations were significantly elevated in adult and pediatric patients with sepsis relative to corresponding healthy adult and pediatric controls, respectively...
May 12, 2018: Journal of Infectious Diseases
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