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https://www.readbyqxmd.com/read/28648331/il-35-as-a-newly-proposed-homeostasis-associated-molecular-pattern-plays-three-major-functions-including-anti-inflammatory-initiator-effector-and-blocker-in-cardiovascular-diseases
#1
Xinyuan Li, Pu Fang, William Y Yang, Hong Wang, Xiaofeng Yang
IL-35 is a new anti-inflammatory cytokine identified in 2007, which inhibits inflammation and immune responses by inducing regulatory T cells and regulatory B cells and suppressing effector T cells and macrophages. The unique initiator and effector anti-inflammatory properties of IL-35 bring tremendous interest in investigating its role during cardiovascular disease (CVD) development, in which inflammatory processes are firmly established as central to its development and complications. In this review, we update recent understanding of how IL-35 is produced and regulated in the cells...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28639230/intracellular-pharmacokinetics-of-antibacterials-and-their-clinical-implications
#2
REVIEW
Federico Pea
The intracellular pharmacokinetics of the different classes of antimicrobials into surrogate markers of tissue accumulation (alveolar macrophages and/or total alveolar cells collected by means of bronchoalveolar lavage or peripheral white blood cells) was reviewed. The aim of this review was to discuss the clinical implications of the intracellular pharmacokinetics of antibacterials, either from the therapeutic or toxicological perspective. The different pharmacokinetic behaviour of antimicrobials within cells is mainly related to their physicochemical properties (hydrophilicity and lipophilicity), and may have several clinical implications...
June 21, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28634421/the-role-of-von-willebrand-factor-in-vascular-inflammation-from-pathogenesis-to-targeted-therapy
#3
REVIEW
Felice Gragnano, Simona Sperlongano, Enrica Golia, Francesco Natale, Renatomaria Bianchi, Mario Crisci, Fabio Fimiani, Ivana Pariggiano, Vincenzo Diana, Andreina Carbone, Arturo Cesaro, Claudia Concilio, Giuseppe Limongelli, Mariagiovanna Russo, Paolo Calabrò
Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions...
2017: Mediators of Inflammation
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
#4
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/28631997/expression-and-purification-of-a-functional-porcine-soluble-triggering-receptor-expressed-on-myeloid-cells-1
#5
Hui Li, Shuangshuang Guo, Leyan Yan, Chunhua Meng, Yiyi Hu, Kongwang He, Zhendan Shi
Triggering receptor expressed on myeloid cells 1 (TREM-1) plays a vital role in the pathogen-triggered amplification loop required for proinflammatory responses. Blockade of TREM-1 signaling may inhibit expansion of sepsis and prolong survival of animals. In the present study, the gene of porcine soluble TREM-1 was cloned and expressed in E. coli. After purification, the bioactivity of recombinant porcine soluble TREM-1 was tested in vitro on porcine alveolar macrophages. The results showed that supplementation with the recombinant porcine sTREM-1 protein rapidly and dose-dependently attenuated the upregulation of cytokines (IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12, IL-16, IL-18, and TNF-α) caused by LPS stimulation in the cultured porcine alveolar macrophages...
February 10, 2017: Animal Biotechnology
https://www.readbyqxmd.com/read/28628912/liver-kinase-b1-amp-activated-protein-kinase-pathway-activation-attenuated-the-progression-of-endotoxemia-in-the-diabetic-mice
#6
Yan Yang, Ruolan Dong, Danli Hu, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
BACKGROUND/AIMS: Sepsis is a common disease that continues to increase in prevalence worldwide, and diabetes mellitus may make the situation worse. This study was designed to determine the role of Liver Kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in diabetic mice complicated with systemic endotoxemia. METHODS: The effects of LKB1/AMPK signaling pathway activation on endotoxemia were investigated in streptozotocin induced diabetic mice (STZ-mice) and db/db diabetic mice...
June 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28611397/identification-of-gxxxxg-motif-in-chrysophsin-1-and-its-implication-in-the-design-of-analogs-with-cell-selective-antimicrobial-and-anti-endotoxin-activities
#7
Amit Kumar Tripathi, Tripti Kumari, Munesh Kumar Harioudh, Pranjal Kumar Yadav, Manoj Kathuria, P K Shukla, Kalyan Mitra, Jimut Kanti Ghosh
Marine fish antimicrobial peptide, chrysophsin-1 possesses versatile biological activities but its non-selective nature restricts its therapeutic possibilities. Often small alterations in structural motifs result in significant changes in the properties of concerned proteins/peptides. We have identified GXXXXG motif in chrysophsin-1. Glycine residue(s) of this motif in Chrysophsin-1 was/were replaced with alanine, valine and proline residue(s). Of these, proline-substituted Chrysophsin-1 analogs exhibited significantly reduced cytotoxicity towards mammalian cells...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611290/a-fragment-of-the-alarmin-prothymosin-%C3%AE-as-a-novel-biomarker-in-murine-models-of-bacteria-induced-sepsis
#8
Pinelopi Samara, Vivi Miriagou, Michael Zachariadis, Olga Mavrofrydi, Vasilis J Promponas, Skarlatos G Dedos, Panagiota Papazafiri, Hubert Kalbacher, Wolfgang Voelter, Ourania Tsitsilonis
Sepsis is a life-threatening condition that requires urgent care. Thus, the identification of specific and sensitive biomarkers for its early diagnosis and management are of clinical importance. The alarmin prothymosin alpha (proTα) and its decapeptide proTα(100-109) are immunostimulatory peptides related to cell death. In this study, we generated bacterial models of sepsis in mice using two Klebsiella pneumoniae strains (L-78 and ATCC 43816) and monitored sepsis progression using proTα(100-109) as a biomarker...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28605238/mucin-1-protects-against-severe-streptococcus-pneumoniae-infection
#9
Poshmaal Dhar, Garrett Z Ng, Eileen M Dunne, Philip Sutton
Streptococcus pneumoniae is a bacterial pathogen that commonly resides in the human nasopharynx, typically without causing any disease. However, in some cases these bacteria migrate from the nasopharynx to other sites of the body such as the lungs and bloodstream causing pneumonia and sepsis, respectively. This study used a mouse model of infection to investigate the potential role of Mucin 1 (MUC1), a cell membrane-associated glycoprotein known for playing a key barrier role at mucosal surfaces, in regulating this process...
June 12, 2017: Virulence
https://www.readbyqxmd.com/read/28601359/osteopontin-exacerbates-pseudomonas-aeruginosa-induced-bacteremia-in-mice
#10
Zhenghao Piao, Haiying Yuan
Osteopontin (OPN) is a multifunctional protein involved in various pathophysiological processes. However, the role of OPN in Pseudomonas aeruginosa-related sepsis is not yet clear. Here, we found that OPN expression was elevated in plasma and spleen samples from P. aeruginosa-infected mice. To determine the function of OPN in sepsis, we used wild-type (WT) and OPN-knockout (KO) mice with P. aeruginosa-induced bacteremia. We found that OPN-KO mice exhibited reduced mortality compared with WT mice and that OPN exacerbated spleen bleeding and functional impairment...
May 30, 2017: Cellular Immunology
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/28586037/transcriptional-co-regulator-rip140-an-important-mediator-of-the-inflammatory-response-and-its-associated-diseases-review
#12
Zhu-Jun Yi, Jian-Ping Gong, Wei Zhang
The inflammatory response is a physiological process that is essential for maintaining homeostasis of the immune system. Inflammation is classified into acute inflammation and chronic inflammation, both of which pose a risk to human health. However, specific regulatory mechanisms of the inflammatory response remain to be elucidated. Receptor interacting protein (RIP) 140 is a nuclear receptor that affects an extensive array of biological and pathological processes in the body, including energy metabolism, inflammation and tumorigenesis...
June 2, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28579909/the-alleviative-effects-of-metformin-for-lipopolysaccharide-induced-acute-lung-injury-rat-model-and-its-underlying-mechanism
#13
Xiangcheng Zhang, Futai Shang, Liangliang Hui, Kui Zang, Gengyun Sun
For patients who have sepsis, acute lung injury (ALI) causes most of death. Metformin (Met) is an anti-hyperglycemic agent and it has extensive pharmacological properties. This study aimed to analyze the influence of Met on lipopolysaccharide (LPS) -induced ALI. Met (1, 2, and 4 mg/kg) were injected and LPS was injected 30 min later. The data suggested Met can reduce release of inflammatory cytokines and bronchoalveolar lavage fluid (BALF) protein expression, reduce lung wet/dry ratio, and significantly improve LPS-induced lung destruction during ALI...
May 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28562479/sepsis-up-regulates-cd14-expression-in-a-myd88-dependent-and-trif-independent-pathway
#14
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/28562476/fn14-blockade-on-pulmonary-microvascular-endothelial-cells-improves-the-outcome-of-sepsis-induced-acute-lung-injury
#15
Yun Zou, Suhong Bao, Fang Wang, Long Guo, Jiali Zhu, Jun Wang, Xiaoming Deng, Jinbao Li
Pulmonary microvascular leakage is one of the characteristics of blood-air barrier dysfunction in septic acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Fibroblast growth factor-inducible 14 (Fn14) exerts diverse functions under certain circumstances. However, the role of Fn14 on the integrity of pulmonary microvascular endothelial cells (PMVECs) during sepsis remains unknown. Septic ALI was induced via cecal ligation and puncture (CLP). Fn14 expression on PMVECs was measured 24 h after surgery...
May 30, 2017: Shock
https://www.readbyqxmd.com/read/28554875/cd39-limits-p2x7-receptor-inflammatory-signaling-and-attenuates-sepsis-induced-liver-injury
#16
Luiz Eduardo Baggio Savio, Paola de Andrade Mello, Vanessa R Figliuolo, Thiago F de Avelar Almeida, Patrícia T Santana, Suellen D S Oliveira, Claudia L M Silva, Linda Feldbrügge, Eva Csizmadia, Richard D Minshall, Maria Serena Longhi, Yan Wu, Simon C Robson, Robson Coutinho-Silva
BACKGROUND & AIMS: The severity of sepsis can be linked to excessive inflammatory responses resulting in hepatic injury with progressive cholestasis. Monocyte/macrophages have been linked to the pathogenesis of cholestasis, cellular injury, and liver failure. P2X7 receptor activation by extracellular ATP (eATP) exacerbates inflammation by augmenting cytokine production; while CD39 scavenges eATP to generate adenosine, thereby limiting P2X7 activation and resulting in A2A receptor stimulation...
May 26, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28539262/synthetic-anti-endotoxin-peptides-inhibit-cytoplasmic-lps-mediated-responses
#17
Anja Pfalzgraff, Lena Heinbockel, Qi Su, Klaus Brandenburg, Günther Weindl
Toll-like receptor (TLR) 4-independent recognition of lipopolysaccharide (LPS) in the cytosol by inflammatory caspases leads to non-canonical inflammasome activation and induction of IL-1 secretion and pyroptosis. The discovery of this novel mechanism has potential implications for the development of effective drugs to treat sepsis since LPS-mediated hyperactivation of caspases is critically involved in endotoxic shock. Previously, we demonstrated that Pep19-2.5, a synthetic anti-endotoxin peptide, efficiently neutralises pathogenicity factors of Gram-negative and Gram-positive bacteria and protects against sepsis in vivo...
May 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28535510/heat-shock-protein-a12b-protects-vascular-endothelial-cells-against-sepsis-induced-acute-lung-injury-in-mice
#18
Yi Chen, Lei Wang, Qiuxiang Kang, Xu Zhang, Guifang Yu, Xiaojian Wan, Jiafeng Wang, Keming Zhu
BACKGROUND: Pulmonary endothelial injury is a critical process in the pathogenesis of acute lung injury (ALI) during sepsis. Heat shock protein A12B (HSPA12B) is mainly expressed in endothelial cells and protects against several harmful factors. However, the effects of HSPA12B in sepsis-induced ALI and its potential mechanisms of action remain unclear. METHODS: For in vivo experiments, C57BL/6 mice were randomly divided into four groups (n=15): a sham operation group, a cecal ligation and puncture (CLP) group, a HSPA12B siRNA-CLP group and a negative control (NC) siRNA-CLP group...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534038/analysis-of-mitochondrial-transfer-in-direct-co-cultures-of-human-monocyte-derived-macrophages-mdm-and-mesenchymal-stem-cells-msc
#19
Megan V Jackson, Anna D Krasnodembskaya
Mesenchymal stem/stromal cells (MSC) are adult stem cells which have been shown to improve survival, enhance bacterial clearance and alleviate inflammation in pre-clinical models of acute respiratory distress syndrome (ARDS) and sepsis. These diseases are characterised by uncontrolled inflammation often underpinned by bacterial infection. The mechanisms of MSC immunomodulatory effects are not fully understood yet. We sought to investigate MSC cell contact-dependent communication with alveolar macrophages (AM), professional phagocytes which play an important role in the lung inflammatory responses and anti-bacterial defence...
May 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28533056/white-matter-damage-after-traumatic-brain-injury-a-role-for-damage-associated-molecular-patterns
#20
REVIEW
Molly Braun, Kumar Vaibhav, Nancy M Saad, Sumbul Fatima, John R Vender, Babak Baban, Md Nasrul Hoda, Krishnan M Dhandapani
Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. Despite decades of pre-clinical investigation, therapeutic strategies focused on acute neuroprotection failed to improve TBI outcomes. This lack of translational success has necessitated a reassessment of the optimal targets for intervention, including a heightened focus on secondary injury mechanisms. Chronic immune activation correlates with progressive neurodegeneration for decades after TBI; however, significant challenges remain in functionally and mechanistically defining immune activation after TBI...
May 19, 2017: Biochimica et Biophysica Acta
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