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sepsis AND anti-inflammatory

Weilan Kong, Kai Kang, Yang Gao, Haitao Liu, Xianglin Meng, Yanhui Cao, Songliu Yang, Wen Liu, Jiannan Zhang, Kaijiang Yu, Mingyan Zhao
Sepsis-induced myocardial injury is a well-known cause of mortality. The cholinergic anti-inflammatory pathway (CHAIP) is a physiological mechanism by which the central nervous system regulates immune response through the vagus nerve and acetylcholine; the α7-nicotinic acetylcholine receptor (α7nAChR) is the main component of CHAIP; GTS-21, a synthetic α7nAChR selective agonist, has repeatedly shown its powerful anti-inflammatory effect. However, little is known about its effect on LPS-induced myocardial injury...
April 21, 2018: Inflammation
Juan Jiang, Hongling Yin, Yao Sun, Huaiqiu Huang, Xuchu Hu
Cyclophilin A (CyPA), ubiquitously existing in cytoplasm of all eukaryotes, can be secreted in response to inflammatory stimuli. Extracellular CyPA plays a prominent role in the pathological processes of inflammatory diseases, acting as a proinflammatory mediator, exerting chemotactic effects, promoting apoptosis of endothelial cells and amplifying ROS generation, thus being considered as a potential treatment target of sepsis, a systemic inflammatory response syndrome. Our previous study found that antibodies against cyclophilin A of Clonorchis sinensis (CsCyPA) could neutralize mouse cyclophilin A (MuCyPA)...
April 18, 2018: International Immunopharmacology
Xingyu Yang, Ruilin Sun, Lei Ci, Ning Wang, Sai Yang, Jiahao Shi, Hua Yang, Mengjie Zhang, Jian Fei
Nfκb2(p52/p100) plays essential roles in many chronic inflammatory diseases. Tracing the dynamic expression of Nfκb2 during different biological processes in vivo can provide valuable clues to understand the biological functions of this gene and develop anti-inflammatory drugs. In this study, B6-Tg(Nfκb2-luc)Mlit transgenic mouse line, a mouse model in which the expression of firefly luciferase gene is under the control of a 14.6-kb mouse Nfκb2 promoter, was generated to monitor the expression of p52/p100 in vivo...
April 19, 2018: Biochemical and Biophysical Research Communications
Asma Ahmed, Komal Dolasia, Sangita Mukhopadhyay
Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli- induced septic peritonitis...
April 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Joann Hsu, John P Donnelly, Ninad S Chaudhary, Justin X Moore, Monika M Safford, Junghyun Kim, Henry E Wang
OBJECTIVE: Sepsis is the syndrome of life-threatening organ dysfunction resulting from dysregulated host response to infection. Aspirin, an anti-inflammatory agent, may play a role in attenuating the inflammatory response during infection. We evaluated the association between aspirin use and long-term rates of sepsis as well as sepsis outcomes. METHODS: We analyzed data from 30,239 adults ≥45 years old in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort...
2018: PloS One
Patrick Hoversten, Joel Beachey, Michael Pham, Anjali Bhagra
A 33-year-old man presented with new-onset, asymmetric, migratory oligoarthritis in the setting of several weeks of nausea and vomiting, diarrhoea, fevers and dysuria. He was initially treated in the inpatient setting with broad-spectrum antibiotics due to concern for an evolving sepsis presentation. Arthrocentesis of a large right knee effusion revealed inflammatory synovial fluid without findings suggestive of septic arthritis. Human leucocyte antigen B27 was positive and, taken together with the antecedent history of gastroenteritis, dysuria and inflammatory oligoarthritis, the clinical diagnosis was most consistent with reactive arthritis...
April 17, 2018: BMJ Case Reports
Gagandeep Singh, Gurjit Singh, Rajbir Bhatti, Mehak Gupta, Ajay Kumar, Ankita Sharma, Mohan Paul Singh Ishar
A library of indolyl-isoxazolidines (6-9) has been synthesized by regio- and stereoselective microwave irradiated 1,3-dipolar cycloadditions of C-(3-indolyl)-N-phenylnitrone (2') with variedly substituted dipolarophiles (3'-5') and screened for their anti-inflammatory activities through inhibition of pro-inflammatory cytokines such as TNF-α and IL-6. Amongst the evaluated compounds (6-9), bicyclic isoxazolidine (9a) was found to exhibit significant inhibitory potential against LPS induced human IL-6 and TNF-α in THP-1 cells...
April 3, 2018: European Journal of Medicinal Chemistry
Wen-Ying Wei, Zhen-Guo Ma, Ning Zhang, Si-Chi Xu, Yu-Pei Yuan, Xiao-Feng Zeng, Qi-Zhu Tang
C1q/tumor necrosis factor-related protein-3 (CTRP3) shows striking homologies of genomic structure to the adiponectin. In this study, we aimed to investigate the protective role of CTRP3 against sepsis-induced cardiomyopathy. Here, we overexpressed CTRP3 in myocardium by direct intramyocardial injection and constructed a model of lipopolysaccharide (LPS)-induced sepsis in mice. Our results demonstrated that cardiac-specific overexpression of CTRP3 remarkably attenuated myocardial dysfunction and increased the phosphorylation level of AMPKα during LPS-induced sepsis...
April 12, 2018: Molecular and Cellular Endocrinology
Jing Wang, Ruiting Li, Zhiyong Peng, Wenhai Zhou, Bo Hu, Xin Rao, Xiao Yang, Jianguo Li
BACKGROUND: Acute lung injury (ALI) is a severe outcome of sepsis. Alveolar macrophages (AMs) play key roles in defense, resolution in ALI. The polarization of AMs is dependent on micro environmental stimuli and might influence the progression of ALI. GTS-21, a selective α7 nicotinic acetylcholine receptor agonist of the cholinergic anti-inflammatory pathway (CAP), has recently been established to be promising in the treatment of ALI. However, the molecular mechanism underlying the GTS-21-mediated suppression of inflammatory responses has been explored only partially...
March 30, 2018: Shock
Brent T Xia, Nadine Beckmann, Leah K Winer, Young Kim, Holly S Goetzman, Rosalie E Veile, Erich Gulbins, Michael D Goodman, Vanessa Nomellini, Charles C Caldwell
During sepsis, the early innate response and inflammatory cytokine cascade are associated with activation of the coagulation cascade. Acute hypercoagulability can contribute to lethal sequela of vascular thrombosis, tissue ischemia, and organ failure. We investigated if amitriptyline (AMIT), an antidepressant drug with a number of anti-inflammatory effects, could ameliorate sepsis in a murine model of sepsis - cecal ligation and puncture (CLP). We hypothesized that AMIT treatment would reduce inflammation and mitigate sepsis-induced coagulopathy...
March 30, 2018: Shock
Xiong Yuyun, Cheng Xi, Yin Qing, Xia Lin, Rui Ke, Sun Bingwei
Sepsis is a severe multisystem disease with high mortality rates and limited treatment options. However, advances during the last decade have opened opportunities to develop novel therapeutic strategies. The Notch signaling pathway plays a critical role in inflammation, and its inhibition offers an avenue to treat inflammatory diseases, such as sepsis. Asiatic acid (AA), a triterpenoid isolated from Centella asiatica, reportedly exerts anti-oxidant, anti-tumor, and anti-inflammatory effects, but its mechanisms remain unclear...
March 13, 2018: Oncotarget
Yarong Zhao, Haiyan Zhu, Haining Wang, Liang Ding, Lizhi Xu, Dai Chen, Sunan Shen, Yayi Hou, Huan Dou
Background: The liver is a vital target for sepsis-related injury, leading to inflammatory pathogenesis, multiple organ dysfunction and high mortality rates. Monocyte-derived macrophage transformations are key events in hepatic inflammation. N1 -[(4-methoxy)methyl]-4-methyl-1,2-benzenediamine (FC-99) previously displayed therapeutic potential on experimental sepsis. However, the underlying mechanism of this protective effect is still not clear. Results: FC-99 treatment attenuated the liver dysfunction in septic mice that was accompanied with reduced numbers of pro-inflammatory Ly6Chi monocytes in the peripheral blood and CD11b+ F4/80lo monocyte-derived macrophages in the liver...
March 13, 2018: Oncotarget
Fang-Hsuean Liao, Te-Haw Wu, Yu-Ting Huang, Wen-Jye Lin, Chun-Jen Su, U-Ser Jeng, Shu-Chen Kuo, Shu-Yi Lin
Endotoxicity originating from a dangerous debris (i.e., lipopolysaccharide, LPS) of gram-negative bacteria is a challenging clinical problem, but no drugs or therapeutic strategies that can successfully address this issue have been identified yet. In this study, we report a sub-nanometer gold sticker that can efficiently block endotoxin activity to protect against sepsis. The ultra-small sticker consists of a gold nanocluster that serves as a flake-like substrate and a coating of short alkyl motifs that act as an adhesive, allowing the sticker to dock with LPS by compacting the intramolecular hydrocarbon chain-chain distance (d-spacing) of lipid A, an endotoxicity active site that can cause overwhelming cytokine induction resulting in sepsis progression...
March 28, 2018: Nano Letters
Alexander Michael Abdelnoor, Soha Mcheik, Nayla S Al AKl
BACKGROUND: Previous studies have demonstrated that flagellin, a component of bacterial flagella, engages Toll- Like receptor 5 (TLR-5) causing the activation of the Myeloid Differentiation Factor-88 (MYD-88) pathway that leads to the production of pro-inflammatory cytokines including Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). In physiological levels cytokines can aid in protection against infectious agents. However, excessive production of cytokines can lead to septic shock during sepsis...
March 26, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
L Ratiani, N Intskirveli, L Goliadze, T Chkhikvadze, L Koptonashvili, E Khuchua
A 65-year-old male patient, unconscious, was admitted into the clinic by the Ambulance. From the patient's medical history it was revealed that several hours before the admission in the clinic the following symptoms were present: shortness of breath, fever, hypotonia, consciousness inhibition, because of which emergency brigade was called and was brought by the Emergency Brigade. The history is loaded by chronic pathologies: myeloma disease, prostate cancer, ciliary arrhythmia, heart failure; received several courses of polichemotherapy, last ten days has been treated for pneumonia with antibiotics of ceftriaxone group in outpatient setting...
February 2018: Georgian Medical News
Catherine M Dickinson, Brian W LeBlanc, Muhammad M Edhi, Daithi S Heffernan, Mohd Hafeez Faridi, Vineet Gupta, William G Cioffi, Xian O'Brien, Jonathan S Reichner
Background: Multi-organ failure occurs during critical illness and is mediated in part by destructive neutrophil-to-endothelial interactions. The β2 integrin receptor, CR3 (complement receptor 3; Mac-1; CD11b/CD18), which binds endothelial intercellular adhesion molecule-1 (ICAM-1), plays a key role in promoting the adhesion of activated neutrophils to inflamed endothelia which, when prolonged and excessive, can cause vascular damage. Leukadherin-1 (LA-1) is a small molecule allosteric activator of CR3 and has been shown to promote adhesion of blood neutrophils to inflamed endothelium and restrict tissue infiltration...
2018: Journal of Intensive Care
Chien-Hsin Chang, Chun-Chieh Hsu, An-Sheng Lee, Shih-Wei Wang, Kung-Tin Lin, Wei-Luen Chang, Hui-Chin Peng, Wen-Chiung Huang, Ching-Hu Chung
BACKGROUND: Antrodia cinnamomea is an indigenous medicinal mushroom in Taiwan, commonly used for the treatment of cancers and inflammatory disorders. 4-acetylantroquinonol B (4AAQB) is one of the active component isolated from the mycelium of A. cinnamomea. However, whether 4AAQB exhibits anti-inflammatory effect is not clear. METHODS: The anti-inflammatory activity of 4AAQB was examined by ELISA to measure the pro-inflammatory cytokines production in lipopolysaccharide (LPS)-simulated RAW264...
March 23, 2018: BMC Complementary and Alternative Medicine
Mohamed A Dkhil, Rami B Kassab, Saleh Al-Quraishy, Mohamed M Abdel-Daim, Rafat Zrieq, Ahmed E Abdel Moneim
Ziziphus spina-christi (L.), a traditional Arabian medicinal herb, has been used by Egyptians (Bedouin and Nubian) to treat inflammatory symptoms and swellings, pain, and heat since long. We aimed to investigate whether Ziziphus spina-christi leaf extract (ZSCLE) exerted a myocardial and renal protective effect on mice in which sepsis had been induced with cecal ligation and puncture (CLP). Male C57BL/6 mice were divided randomly into six groups (n = 7): sham-operated group, sham-operated mice treated with ZSCLE (300 mg/kg), CLP-induced sepsis group, ZSCLE (100 mg/kg)-treated group, ZSCLE (200 mg/kg)-treated group, and ZSCLE (300 mg/kg)-treated group...
March 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yizi Xia, Ying Chen, Luming Tang, Zheng Wang, Yu Zheng
Acute kidney injury (AKI) is a severe complication of sepsis with a high mortality and morbidity. Pterostilbene (Pte) has been suggested to confer anti-apoptotic and anti-inflammatory effects. In the current study, the effects of Pte on AKI were evaluated in septic mice. Cecal ligation and puncture surgery was performed to induce sepsis. The results suggested that Pte administration significantly decreased the levels of serum urea nitrogen and creatinine, and improved the survival rate of septic mice. Additionally, the renal injury induced by sepsis was attenuated by pterostilbene treatment...
April 2018: Experimental and Therapeutic Medicine
Shujun Zhou, Gui Wang, Wenbin Zhang
The present study aimed to investigate the effects of the Toll-like receptor (TLR)4/myeloid differentiation primary response (MyD)88 signaling pathway on sepsis-associated acute respiratory distress syndrome (ARDS) in rats, and the involvement of macrophage activation and the inflammatory response. A total of 36 specific pathogen-free male Sprague-Dawley rats were selected to establish the rat model of sepsis-associated ARDS using cecal ligation and puncture (CLP). Rats were assigned into the Ab (anti-TLR4 monoclonal antibody)-CLP, CLP and Sham groups...
April 2018: Experimental and Therapeutic Medicine
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