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https://www.readbyqxmd.com/read/28650427/roflumilast-reverses-polymicrobial-sepsis-induced-liver-damage-by-inhibiting-inflammation-in-mice
#1
Hongfang Feng, Jiajia Chen, Haitao Wang, Yufang Cheng, Zhengqiang Zou, Qiuping Zhong, Jiangping Xu
Sepsis is a life-threatening syndrome accompanied by an overwhelming inflammatory response and organ dysfunction. Selective targeting of phosphodiesterase 4 (PDE4) is currently being investigated as an effective therapeutic approach for inflammation-associated diseases. Roflumilast is a selective PDE4 inhibitor, used for the treatment of severe chronic obstructive pulmonary disease in clinic. However, its role in the treatment of sepsis-induced liver damage remains unclear. In the present study, we evaluated the effects of roflumilast in mice with cecal ligation and puncture-induced sepsis, and investigated the underlying mechanism...
June 26, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28648928/pg2-a-botanically-derived-drug-extracted-from-astragalus-membranaceus-promotes-proliferation-and-immunosuppression-of-umbilical-cord-derived-mesenchymal-stem-cells
#2
Yu-Hua Chao, Kang-Hsi Wu, Chiao-Wen Lin, Shun-Fa Yang, Wan-Ru Chao, Ching-Tien Peng, Han-Ping Wu
ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus membranaceus is used to manage the deficiency of vital energy in traditional Chinese medicine and confirmed to have many biological functions. Mesenchymal stem cells (MSCs) possess immunosuppressive effects, and are widely used for regenerative medicine and immune disorders. AIMS OF STUDY: This study investigated the effects of Astragalus polysaccharides (APS) on umbilical cord-derived MSCs (UCMSCs), including morphology, surface marker expression, proliferation, differentiation, and in-vitro and in-vivo immunosuppressive capacities...
June 22, 2017: Journal of Ethnopharmacology
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
#3
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
#4
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/28633555/glutamine-administration-in-early-or-late-septic-phase-downregulates-lymphocyte-pd-1-pd-l1-expression-and-the-inflammatory-response-in-mice-with-polymicrobial-sepsis
#5
Ya-Mei Hu, Yuan-Chin Hsiung, Man-Hui Pai, Sung-Ling Yeh
BACKGROUND: Sepsis is a severe inflammatory response to infection. Excessive compensation to inflammation leads to dysregulated immune response that ultimately results in organ damage and lethality of sepsis. This study administered glutamine (GLN) in the early or late phase of sepsis to investigate its effects on regulating leukocyte programmed cell death 1 (PD-1) and its ligand (programmed cell death ligand 1 [PD-L1]) expression, macrophage function, inflammation, and acute kidney injury in sepsis...
March 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28632510/itraq-based-quantitative-proteomic-analysis-of-lungs-in-murine-polymicrobial-sepsis-with-hydrogen-gas-treatment
#6
Yingxue Bian, Chao Qin, Yuchang Xin, Yang Yu, Hongguang Chen, Guolin Wang, Keliang Xie, Yonghao Yu
Sepsis-associated acute lung injury (ALI), which carries a high morbidity and mortality in patients, has no effective therapeutic strategies to date. Our group have already reported that hydrogen gas (H2) exerts a protective effect against sepsis in mice. However, the molecular mechanisms underlying H2 treatment are not fully understood. This study investigated the effects of H2 on lung injuries in septic mice through the iTRAQ-based quantitative proteomic analysis. Male ICR mice used in this study were subjected to cecal ligation and puncture (CLP) or sham operation...
June 19, 2017: Shock
https://www.readbyqxmd.com/read/28625915/high-fat-diet-induced-obesity-increases-myocardial-injury-and-alters-cardiac-stat3-signaling-in-mice-after-polymicrobial-sepsis
#7
Theodore DeMartini, Marchele Nowell, Jeanne James, Lauren Williamson, Patrick Lahni, Hui Shen, Jennifer M Kaplan
Little is known about how obesity affects the heart during sepsis and we sought to investigate the obesity-induced cardiac effects that occur during polymicrobial sepsis. Six-week old C57BL/6 mice were randomized to a high fat (HFD) (60% kcal fat) or normal diet (ND) (16% kcal fat). After 6 wks of feeding, mice were anesthetized with isoflurane and polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Plasma and cardiac tissue were obtained for analysis. Echocardiography was performed on a separate cohort of mice at 0 and 18h after CLP...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28625265/-protective-effect-of-curcumin-on-hepatocytes-in-rats-with-sepsis
#8
Haiyan Yin, Minshan Qiu, Dan He, Rui Zhang, Pei Tao, Yanwen Liang, Yuegui Yang, Yanqi Guo, Xiaoling Ye
OBJECTIVE: To investigate the protective effect of curcumin on hepatocytes in rats with sepsis. METHODS: Eighty healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, Xuebijing group and curcumin group (20 rats in each group) according to the random number table method. The animal model of sepsis was established by cecal ligation and puncture (CLP). In the sham operation group, the cecum was removed only after the operation...
February 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28623379/cathelicidin-deficient-mice-exhibit-increased-survival-and-upregulation-of-key-inflammatory-response-genes-following-cecal-ligation-and-puncture
#9
Patricia Severino, Suely Kubo Ariga, Hermes Vieira Barbeiro, Thais Martins de Lima, Elisangela de Paula Silva, Denise Frediani Barbeiro, Marcel Cerqueira César Machado, Victor Nizet, Fabiano Pinheiro da Silva
Antimicrobial peptides possess a myriad of molecular properties including bacterial killing and the regulation of many aspects of innate immunity. Cathelicidins are a group of antimicrobial peptides widely investigated by the scientific community. Many studies have focused on the bactericidal and pro-inflammatory roles of cathelicidins. Because the role of endogenous cathelicidin expression remains obscure in deep-seated systemic infections, we induced sepsis in cathelicidin knockout and wild-type (WT) mice by cecal ligation and puncture, performing transcriptome screening by DNA microarray in conjunction with other immunologic assays...
June 16, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28616781/impact-of-hyperglycemia-on-cystathionine-%C3%AE-lyase-expression-during-resuscitated-murine-septic-shock
#10
Tamara Merz, Josef A Vogt, Ulrich Wachter, Enrico Calzia, Csaba Szabo, Rui Wang, Peter Radermacher, Oscar McCook
BACKGROUND: Cystathionine-γ-lyase (CSE) was shown to have a regulatory role in glucose metabolism. Circulatory shock can induce metabolic stress, thereby leading to hyperglycemia and mitochondrial dysfunction. In vitro data suggest an effect of high glucose on CSE expression. Therefore, the aim of this study was to investigate the effects of hyperglycemia on CSE expression in resuscitated murine septic shock. METHODS: Normo- (80-150 mg/dl) and hyperglycemic (>200 mg/dl) male C57/BL6J mice (n = 5-6 per group) underwent cecal ligation and puncture (CLP)-induced polymicrobial sepsis or sham procedure (n = 6 per group) and, 15 h afterwards, were anesthetized again, surgically instrumented and received intensive care treatment, including antibiotics, lung protective mechanical ventilation, circulatory support, and intravenous (i...
December 2017: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/28601327/milk-fat-globule-epidermal-growth-factor-factor-viii-attenuates-sepsis-induced-acute-kidney-injury
#11
Cindy Cen, Monowar Aziz, Weng-Lang Yang, Mian Zhou, Jeffrey M Nicastro, Gene F Coppa, Ping Wang
BACKGROUND: Acute kidney injury (AKI) is most commonly caused by sepsis in critically ill patients, and it is associated with high morbidity and mortality. The pathophysiology of sepsis-induced AKI is generally accepted to include direct inflammatory injury, endothelial cell dysfunction, and apoptosis. Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein with a known role in the enhancement of apoptotic cell clearance and regulation of inflammation...
June 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28598488/myosin-light-chain-kinase-knockout-improves-gut-barrier-function-and-confers-a-survival-advantage-in-polymicrobial-sepsis
#12
C Adam Lorentz, Zhe Liang, Mei Meng, Ching-Wen Chen, Benyam P Yoseph, Elise R Breed, Rohit Mittal, Nathan J Klingensmith, Alton B Farris, Eileen M Burd, Michael Koval, Mandy L Ford, Craig M Coopersmith
Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK(-/-) and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies...
June 7, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28597756/lack-of-elevation-in-plasma-levels-of-pro-inflammatory-cytokines-in-common-rodent-models-of-pulmonary-arterial-hypertension-questions-of-construct-validity-for-human-patients
#13
Kenny Schlosser, Mohamad Taha, Yupu Deng, Baohua Jiang, Lauralyn A McIntyre, Shirley Hj Mei, Duncan J Stewart
Translational research depends on the relevance of animal models and how well they replicate human disease. Here, we investigated plasma levels of three important pro-inflammatory cytokines (TNFα, IL-6, and MCP-1), known to be elevated in human pulmonary arterial hypertension (PAH), and systematically assessed their levels in PAH patients compared to five different rodent models of pulmonary hypertension (PH). A consistent immunoassay platform (Luminex xMAP) and source (Millipore) was used to measure all specimens...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28595959/cudratricusxanthone-a-attenuates-renal-injury-in-septic-mice
#14
Wonhwa Lee, Yuri Lee, Gil-Saeng Jeong, Sae-Kwang Ku, Jong-Sup Bae
As a natural compound extracted from the roots of Cudrania tricuspidata Bureau, Cudratricusxanthone A (CTXA) is known to possess hepatoprotective, anti-inflammatory, and anti-proliferative activities. This study was aimed to clarify the role of CTXA in modulating renal functional damage in a mouse model of sepsis and to elucidate its underlying mechanisms. We examined the renal protective effects of CTXA on cecal ligation and puncture (CLP)-induced renal damage by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity...
June 12, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28591008/plasma-resuscitation-improved-survival-in-a-cecal-ligation-and-puncture-rat-model-of-sepsis
#15
Ronald Chang, John B Holcomb, Par I Johansson, Shibani Pati, Martin A Schreiber, Charles E Wade
BACKGROUND: The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-hour survival in a rat sepsis model. METHODS: Adult male Sprague-Dawley rats (375-425 g) were subjected to 35% cecal ligation and puncture (CLP) (t = 0 h)...
June 6, 2017: Shock
https://www.readbyqxmd.com/read/28589293/impairment-of-osmotic-challenge-induced-neurohypophyseal-hormones-secretion-in-sepsis-survivor-rats
#16
Nilton Nascimento Santos-Junior, Luís Henrique Angenendt Costa, Carlos Henrique Rocha Catalão, Alexandre Kanashiro, Tarek Sharshar, Maria José Alves Rocha
BACKGROUND/PURPOSE: Recent studies have reported that sepsis survivors show impaired central nervous system functions. The osmoregulation in this post-sepsis condition has not been well investigated. In the present study, we evaluated the secretion of neurohypophyseal hormones, arginine vasopressin (AVP) and oxytocin (OT), and water intake induced by osmotic challenge in survivor rats. METHODS: Wistar rats were submitted to sepsis by cecal ligation and puncture (CLP)...
June 6, 2017: Pituitary
https://www.readbyqxmd.com/read/28576491/blockage-of-glycolysis-by-targeting-pfkfb3-alleviates-sepsis-related-acute-lung-injury-via-suppressing-inflammation-and-apoptosis-of-alveolar-epithelial-cells
#17
Yuanqi Gong, Haibing Lan, Zhihong Yu, Meng Wang, Shu Wang, Yu Chen, Haiwei Rao, Jingying Li, Zhiyong Sheng, Jianghua Shao
Sepsis-related acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells resulting in acute hypoxemic respiratory failure. Recent studies indicated that anaerobic glycolysis play an important role in sepsis. However, whether inhibition of aerobic glycolysis exhibits beneficial effect on sepsis-induced ALI is not known. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was set up and mice treated with glycolytic inhibitor 3PO after CLP...
May 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28572445/complement-induced-activation-of-mapks-and-akt-during-sepsis-role-in-cardiac-dysfunction
#18
Fatemeh Fattahi, Miriam Kalbitz, Elizabeth A Malan, Elizabeth Abe, Lawrence Jajou, Markus S Huber-Lang, Markus Bosmann, Mark W Russell, Firas S Zetoune, Peter A Ward
Polymicrobial sepsis in mice causes myocardial dysfunction after generation of the complement anaphylatoxin, complement component 5a (C5a). C5a interacts with its receptors on cardiomyocytes (CMs), resulting in redox imbalance and cardiac dysfunction that can be functionally measured and quantitated using echocardiology/Doppler technology. In this report we have evaluated activation of MAPKs and Akt in CMs exposed to C5a in vitro and after cecal ligation and puncture (CLP) in vivo In both cases, C5a in vitro caused activation (phosphorylation) of MAPKs and Akt in CMs, which required availability of both C5a receptors...
June 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28562479/sepsis-up-regulates-cd14-expression-in-a-myd88-dependent-and-trif-independent-pathway
#19
Zhixia Chen, Zhenzhen Shao, Shuya Mei, Zhengzheng Yan, Xibing Ding, Timothy Billiar, Quan Li
An overwhelming immune response, particularly from macrophages, plays a critical role in survival and organ damage in sepsis patients. TLRs are important receptors to recognize the conserved motifs expressed by invading bacteria. The TLRs except TLR3 signal via a MyD88 dependent pathway. TLR3 uses a TRIF dependent pathway, while TLR4 uses both MyD88 and TRIF dependent pathways. Previous studies indicated that CD14 was necessary for TLRs dependent production of pro-inflammatory cytokines. Blocking CD14 protected against the deleterious systemic inflammatory response associated with sepsis...
May 29, 2017: Shock
https://www.readbyqxmd.com/read/28562477/sepsis-induced-channelopathy-in-skeletal-muscles-is-associated-with-expression-of-non-selective-channels
#20
Elisa Balboa, Fujiko Saavedra, Luis A Cea, Aníbal A Vargas, Valeria Ramírez, Rosalba Escamilla, Juan C Sáez, Tomás Regueira
Skeletal muscles (∼50% of the body weight) are affected during acute and late sepsis and represent one sepsis associate organ dysfunction. Cell membrane changes has been proposed to result from a channelopathy of yet unknown cause associated to mitochondrial dysfunction and muscle atrophy. We hypothesize that the channelopathy might be explained at least in part by the expression of non-selective channels. Here, this possibility was studied in a characterized mice model of late sepsis with evident skeletal muscle atrophy induced by cecal ligation and puncture (CLP)...
May 30, 2017: Shock
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