: Previous studies have indicated that the monocyte chemo-attractant protein 1 (MCP-1), also referred to as C-C motif chemokine ligand 2 (CCL2), plays a significant role in the pathogenesis of sepsis, and this study investigated the clinical relevance of two MCP-1 gene polymorphisms on sepsis onset and progression. The Multiplex SNaPshot genotyping method was used to detect MCP-1 gene polymorphisms in the Chinese Han population (403 sepsis patients and 400 controls). MCP-1 mRNA expression levels were measured using real-time quantitative PCR, and enzyme-linked immunosorbent assays were used to analyze MCP-1, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and interleukin-1 beta (IL-1β) plasma concentrations. The rs1024611 polymorphism analysis showed lower frequencies of minor homozygous genotype (AA) and allele (A) in sepsis patients compared to the healthy controls (19.4% vs. 31.5%, P = 0.0001 and 45.9% vs. 54.8%, P = 0.0004, respectively). And the frequencies of GG genotype and G allele were lower in sepsis patients compared to the controls (19.6% vs. 31.3%, P = 0.0002 and 46.0% vs. 54.5%, P = 0.0007, respectively). The rs1024611 AG/GG and rs2857656 GC/CC genotypes were both overrepresented in patients with severe sepsis (both P = 0.0005) and septic shock (P = 0.010 and P = 0.015, respectively) compared to the patients with mild sepsis. Moreover, among sepsis patients, the rs1024611 AG/GG and rs2857656 GC/CC carriers exhibited significant increases in expression levels of MCP-1 (P = 0.025), TNF-α (P = 0.034) and IL-6 (P = 0.043) compared with the rs1024611 AA or rs2857656 GG carriers. This study provides valuable clinical evidence that the MCP-1/CCL2 polymorphisms rs1024611 and rs2857656 are associated with sepsis susceptibility and development. We conclude that MCP-1/CCL2 plays a significant role in the pathogenesis of sepsis, which has potentially important therapeutic implications.
Receptor for advanced glycation end products (RAGE) is considered a major pattern recognition receptor, which plays an important role in the development of sepsis. Increasing evidence showed an association between RAGE polymorphisms and the susceptibility to several inflammatory-related diseases. However, little is known about the clinical relationship between RAGE polymorphisms and sepsis. In this study, we analyzed the association of sepsis with three functional RAGE gene polymorphisms (rs1800...
Data on sepsis prevalence on the general wards is lacking on the UK and in the developed world. We conducted a multicentre, prospective, observational study of the prevalence of patients with sepsis or severe sepsis on the general wards and Emergency Departments (ED) in Wales. During the 24-hour study period all patients with NEWS≥3 were screened for presence of 2 or more SIRS criteria. To be eligible for inclusion, patients had to have a high clinical suspicion of an infection, together with a ...
Background: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to play a significant role in the pathogenesis of sepsis. However, little is known about the clinical relevance of ADAM17 polymorphisms to sepsis onset and development. Methods: This study analyzed the associations of five ADAM17 promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and rs11689958) with sepsis (370 sepsis cases and 400 controls). Genotyping was performed using pyrosequencing and polyme...
Last. Derek C. Angus(University of Pittsburgh)H-Index: 128
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Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. Objective To evaluate and, as needed, update definitions for sepsis and septic shock. Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epide...
#1Yu Wen Li(SYSU: Sun Yat-sen University)H-Index: 2
#2Ci Qiu Yang(SYSU: Sun Yat-sen University)H-Index: 1
Last. Min Hu Chen(SYSU: Sun Yat-sen University)H-Index: 16
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Objective The monocyte chemoattractant protein-1 (MCP-1) -A2518G gene polymorphism has been found to be involved in the susceptibility to inflammatory bowel disease (IBD); however, the results of existing studies are controversial. The aim of this meta-analysis was to assess the relationship between the MCP-1 -A2518G polymorphism and the risk of IBD. Methods PubMed, EMBASE and MEDLINE were searched for studies assessing the relationship between the -A2518G polymorphism in MCP-1 gene and the risk...
Sepsis—a complication of infection—is a factor in at least a third of all hospital deaths—a sobering statistic ( 1 ). Patients with sepsis frequently present with fever, shock, and multiorgan failure. Because of this dramatic clinical scenario, investigators have generally assumed that sepsis mortality is due to unbridled inflammation ( 2 ). Research in animal models, in which administration of the cytokines tumor necrosis factor–α (TNF-α) and interleukin-1 (IL-1) reproduced many features of sep...
#2Yan Gao(HMU: Harbin Medical University)H-Index: 1
Last. Keshen Li(Guangdong Medical College)H-Index: 24
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Introduction Although genetic variants of the A disintegrin and metalloproteinase 10 (ADAM10) gene have been shown to be associated with susceptibility to several inflammatory-related diseases, to date little is known about the clinical relationship in the development of sepsis.
#1Hanan Slimani(University of Colorado Denver)H-Index: 1
#2Yufeng Zhai(University of Colorado Denver)H-Index: 21
Last. Xianzhong Meng(University of Colorado Denver)H-Index: 62
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Introduction Endotoxemia and the systemic inflammatory response syndrome have a significant impact on post-surgery outcome, particularly in the elderly. The cytokine response to endotoxin is altered by aging. We tested the hypothesis that vulnerability to endotoxemic cardiac depression increases with aging due to age-related augmentation of myocardial inflammatory responses.
Objective Autophagy is the regulated catabolic process for recycling damaged or unnecessary organelles, which plays crucial roles in cell survival during nutrient deficiency, and innate immune defense against pathogenic microorganisms. Autophagy has been also reported to be involved in various conditions including inflammatory diseases. IRGM (human immunity-related GTPase) has an important function in eliminating Mycobacterium tuberculosis from host cells via autophagy. We examined the associati...
Sepsis is an extremely complex clinical syndrome, usually involving an excessive inflammatory response including an overshooting cytokine release that damages tissue and organs of the patient. Due to the severity of this condition, it is estimated that over 11 million people die from sepsis each year. Despite intensive research in the field, there is still no specific therapy for sepsis. Many sepsis patients show a marked deficiency of vitamin C. 9 out of 10 sepsis patients have a hypovitaminosi...
Nucleotide-binding domain and leucine-rich repeat (LRR)-containing family protein 3 (NLRP3) regulated the maturation of inflammation-related cytokines by forming NLRP3 inflammasome, which plays pivotal roles in sepsis pathogenesis. In this study, we evaluated the genetic association of NLRP3 polymorphisms with sepsis (640 patients and 769 controls) and characterized the impact of NLRP3 polymorphisms on NLRP3 expression and inflammatory responses. No significant differences were observed in genot...
Last. Ming Liu(Dalian Medical University)H-Index: 4
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Background: Hepatitis C virus (HCV) infection is a global public health burden. Chronic HCV infection leads to the development of fibrosis, cirrhosis, liver cancer, and liver failure over time.Methods: A total of 250 patients with chronic HCV infection and 299 healthy blood donors were recruited. Sixteen candidate single nucleotide polymorphisms (SNPs) in chemokine (C-C motif) ligand 2 (CCL2), CCL5, CCL8, C-C chemokine receptor 2 (CCR2), and CCR5 were genotyped in all participants.Results: The r...
Last. Jonathan J. Magaña(Tec: Monterrey Institute of Technology and Higher Education)H-Index: 15
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Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated response to an infection that is common among patients with moderate to severe burn injury. Previously, genomic variants in Toll-like receptor 4 (TLR4), a key innate immunity receptor, have been associated with sepsis and infection susceptibility. In this study, the association of six TLR4 SNPs with sepsis after burn injury was tested in the Mexican mestizo population. We found that the rs2737190 polymorphism is as...
The mechanisms of how obesity contributes to the development of cardio-metabolic diseases are not entirely understood. Obesity is frequently associated with adipose tissue dysfunction, characterized by, e.g., adipocyte hypertrophy, ectopic fat accumulation, immune cell infiltration, and the altered secretion of adipokines. Factors secreted from adipose tissue may induce and/or maintain a local and systemic low-grade activation of the innate immune system. Attraction of macrophages into adipose t...
The regulatory elements controlling gene expression during acute inflammation are not fully elucidated. Here we report the identification of a set of NF-κB-bound elements and common chromatin landscapes underlying the acute inflammatory response across cell-types and mammalian species. Using primary vascular endothelial cells (human/mouse/bovine) treated with the pro−inflammatory cytokine, Tumor Necrosis Factor-α, we identify extensive (~30%) conserved orthologous binding of NF-κB to accessible,...
Recent studies underline a potential role of autoimmune and genetic disturbances in this disorder pathogenesis. Variants in genes related to inflammatory processes may possibly predispose to chroni...
Growing evidence indicated that single nucleotide polymorphisms (SNPs) in the apolipoprotein E (APOE) gene are related to increase the risk of many inflammatory-related diseases. However, few genetic studies have associated the APOE gene polymorphism with sepsis. This study was to investigate the clinical relevance of the APOE gene polymorphism in the onset and progression of sepsis. A multicenter case-control association study with a large sample size (601 septic patients and 699 healthy indivi...
Abstract Background Standard treatment for diffuse peritonitis due to colorectal perforation may be insufficient to suppress inflammatory reaction in sepsis. Thus, developing new treatments is important. This study aimed to examine whether intraperitoneal irradiation by artificial sunlight suppresses inflammatory reaction in a lipopolysaccharide (LPS)-induced peritonitis model after surgical treatments. Materials and methods Mice were divided into naive, nontreatment (NT), and phototherapy (PT) ...
Abstract Background Diabetic foot ulcer (DFU) is one of the frequent diabetic problems, and the main reason for hospitalization and lower extremity amputation, among patients with type 2 diabetes mellitus (T2DM). The factors correlated with vascular functions and angiogenesis may be involved in the development and prevalence of DFU. Monocyte chemoattractant protein-1 (MCP-1) is a pro-inflammatory cytokine, playing a principal role in the inflammatory process. The influence of MCP-1 –2518A/G poly...