Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment / 中国中药杂志

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.

PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity / 中华医学杂志(英文版)

BACKGROUND@#Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients.@*METHODS@#A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality.@*RESULTS@#The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1.@*CONCLUSIONS@#Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

miR-139-5p protects septic mice with acute lung injury by inhibiting Toll-like receptor 4/Myeloid differentiation factor 88/Nuclear factor-&mac_kgr; B signaling pathway

OBJECTIVES: To investigate the role of miR-139-5p and the TLR4/MyD88/NF-κB signaling pathway in acute lung injury in septic mice. METHOD: A total of 140 healthy male SPF C57BL/6 mice were divided into seven groups, i.e., Normal, Control, NC, miR-139-5p mimic, miR-139-5p inhibitor, TAK-242, and miR-139-5p inhibitor+TAK-242 groups. The levels of miR-139-5p, proteins related to the TLR4/MyD88/NF-κB signaling pathway (TLR4, MyD88, and p-NF-κB p50), and MPO, SOD, GSH, and MDA in lung tissue were measured. The lung tissue wet-to-dry mass ratio (W/D), arterial oxygen partial pressure (PaO2), and carbon dioxide partial pressure (PaCO2) were measured. RESULTS: A web-based bioinformatic tool predicted that MyD88 was a target of miR-139-5p, which was verified by a dual luciferase reporter assay. Compared with those in the Normal group, the levels of miR-139-5p, PaO2, SOD, and GSH were significantly lower, while those of TLR4, MyD88, p-NF-κB p50, W/D, PaCO2, IL-1β, TNF-α, IL-6, MPO, and MDA were higher in all other groups. Moreover, compared with their levels in the Control group, these indicators exhibited contrasting results in the miR-139-5p mimic and TAK-242 groups, but were similar in the miR-139-5p inhibitor group. In the miR-139-5p inhibitor+TAK-242 group, acute lung injury, aggravated by miR-139-5p inhibitor, was partially rescued by TAK-242. CONCLUSION: miR-139-5p inhibits the TLR4/MyD88/NF-κB signaling pathway to alleviate acute lung injury in septic mice.

Mechanism and experimental verification of Dachengqi Decoction in treatment of sepsis based on network pharmacology / 中国中药杂志

This study aims to predict the material basis and mechanism of Dachengqi Decoction in the treatment of sepsis based on network pharmacology. The chemical constituents and targets of Dachengqi Decoction were retrieved from TCMSP, UniPot and DrugBank and the targets for the treatment of sepsis from OMIM and GeneCards. The potential targets of Dachengqi Decoction for the treatment of sepsis were screened by OmicShare. STRING database and Cytoscape 3.7.2 were used to construct the Chinese medicinal-active component-target-disease, active component-key target-key pathway, and protein-protein interaction(PPT) networks. The gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed by DAVID(P<0.05). Finally, the animal experiment was conducted to verify some targets and pathways. A total of 40 active components and 157 targets of the Dachengqi Decoction, 2 407 targets for the treatment of sepsis, and 91 common targets of the prescription and the disease were also obtained. The key targets were prostaglandin G/H synthase 2(PTGS2), prostaglandin G/H synthase 1(PTGS1), protein kinase cAMP-dependent catalytic-α(PRKACA), coagulation factor 2 receptor(F2 R), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic gamma subunit(PIK3 CG), dipeptidyl peptidase 4(DPP4), etc. A total of 533 terms and 125 pathways were obtained for the 91 targets. The main terms were the response to drug, negative regulation of apoptotic process, positive regulation of nitric oxide biosynthetic process and lipopolysaccharide-mediated signaling pathway, and the pathways included pathways in cancer, hepatitis B, and phosphatidylinositol 3-kinase and protein kinase B(PI3 K/Akt) signaling pathway. The animal experiment confirmed that Dachengqi Decoction can down-regulate inflammatory cytokines interleukin-1β(IL-1β), IL-6 and tumor necrosis factor α(TNF-α)(P<0.01). It could also reduce the wet/dry weight ratio of lung tissue, the level of myeloperoxidase(MPO) and the phosphorylation of PI3 K and Akt(P<0.01). These results indicated that Dchengqi Decoction could act on inflammation-related targets and improve sepsis by inhibiting PI3 K/Akt signaling pathway. The animal experiment supported the predictions of network pharmacology. Dachengqi Decoction intervenes sepsis via multiple components, multiple targets, and multiple pathways. The result lays a foundation for further research on the mechanism of Dachengqi Decoction in the treatment of sepsis.

Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways associated with sepsis-related ARDS based on a public microarray dataset and to further explore the molecular mechanism of ARDS. RESULTS: A total of 122 up-regulated DEGs and 91 down-regulated differentially expressed genes (DEGs) were obtained. The up- and down-regulated DEGs were mainly involved in functions like mitotic cell cycle and pathway like cell cycle. Protein-protein interaction network of ARDS analysis revealed 20 hub genes including cyclin B1 (CCNB1), cyclin B2 (CCNB2) and topoisomerase II alpha (TOP2A). A total of seven transcription factors including forkhead box protein M1 (FOXM1) and 30 target genes were revealed in the transcription factor-target gene regulation network. Furthermore, co-cited genes including CCNB2-CCNB1 were revealed in literature mining for the relations ARDS related genes. CONCLUSIONS: Pathways like mitotic cell cycle were closed related with the development of ARDS. Genes including CCNB1, CCNB2 and TOP2A, as well as transcription factors like FOXM1 might be used as the novel gene therapy targets for sepsis related ARDS

A validation of the construct and reliability of an emotional intelligence scale applied to nursing students / Validação do construto e da confiabilidade de uma escala de inteligência emocional aplicada a estudantes de enfermagem / Validación de constructo y confiabilidad de la escala de inteligencia emocional en estudiantes de enfermería

OBJECTIVE: The current study aimed to validate the construct and reliability of an emotional intelligence scale. METHOD: The Trait Meta-Mood Scale-24 was applied to 349 nursing students. The process included content validation, which involved expert reviews, pilot testing, measurements of reliability using Cronbach's alpha, and factor analysis to corroborate the validity of the theoretical model's construct. RESULTS: Adequate Cronbach coefficients were obtained for all three dimensions, and factor analysis confirmed the scale's dimensions (perception, comprehension, and regulation). CONCLUSION: The Trait Meta-Mood Scale is a reliable and valid tool to measure the emotional intelligence of nursing students. Its use allows for accurate determinations of individuals' abilities to interpret and manage emotions. At the same time, this new construct is of potential importance for measurements in nursing leadership; educational, organizational, and personal improvements; and the establishment of effective relationships with patients. .

OBJETIVO: este estudo tem como objetivo validar o construto e a confiabilidade de uma escala de inteligência emocional. MÉTODO: a escala Trait Meta-Mood Scale-24 foi aplicada em 349 estudantes de enfermagem. O processo envolveu a validação do conteúdo, que compreendeu avaliações de especialistas, testes piloto, medição da confiabilidade utilizando o coeficiente alfa de Cronbach e análise fatorial para corroborar a validade do construto do modelo teórico. RESULTADOS: coeficientes de Cronbach adequados foram obtidos nas três dimensões e a análise fatorial confirmou as dimensões da escala (percepção, compreensão e regulação). CONCLUSÃO: a Trait Meta-Mood Scale-24 é um instrumento confiável e válido para medir a inteligência emocional de estudantes de enfermagem. Seu uso permite determinar precisamente a capacidade dos indivíduos de interpretar e gerenciar emoções. Ao mesmo tempo, esse novo construto é de potencial importância para medidas em liderança em enfermagem; para o aperfeiçoamento educacional, organizacional e pessoal e para o estabelecimento de relacionamentos eficazes com os pacientes. .

OBJETIVO: efectuar la validación de constructo y confiabilidad de una escala de inteligencia emocional. MÉTODO: se aplicó la Trait-Meta Mood Scale-24 a 349 estudiantes de enfermería. El proceso comprendió la validación de contenido que consistió en lo siguiente: revisión por expertos; prueba piloto; medición de la confiabilidad por medio del Alfa de Cronbach; y comprobación de la validez de constructo del modelo teórico a través del Análisis Factorial. RESULTADOS: se obtuvieron adecuados coeficientes de Cronbach en las tres dimensiones, y el análisis factorial confirmó las dimensiones de la escala (percepción, comprensión y regulación). CONCLUSIÓN: la Trait-Meta Mood Scale es un instrumento confiable y válido para medir la inteligencia emocional en estudiantes de enfermería. Su uso permite identificar habilidades para interpretar y manejar las emociones. Es a la vez un nuevo constructo de potencial importancia para el liderazgo de enfermería; éste ayudará a mejorar aspectos educacionales, organizacionales y personales; además, favorecerá una relación efectiva con los pacientes. .

HLA-A*31 como marcador de suscetibilidade genetica em sepse / HLA-A*31 as a marker of genetic susceptibility to sepsis

Objetivo: Haplótipos do HLA têm sido associados a muitas doenças autoimunes, mas não foi descrita qualquer associação na sepse. O objetivo desse estudo é investigar o sistema HLA como um possível marcador de suscetibilidade genética à sepse. Métodos: Estudo prospectivo de coorte, incluindo pacientes admitidos em unidade de terapia intensiva e controles-saudáveis obtidos em lista de doadores de transplante renal. Foram excluídos pacientes abaixo dos 18 anos de idade, gestantes ou HIV positivos, pacientes com doença maligna metastática ou sob quimioterapia, pacientes com hepatopatia avançada, com condições de fim de vida. O DNA foi extraído de sangue total, e a haplotipagem de HLA foi realizada com a tecnologia MiliPlex®. Resultados: Foram incluídos 1.121 pacientes (1.078 doadores de rim, 20 pacientes com sepse grave e 23 pacientes admitidos por choque séptico) entre outubro de 2010 e outubro de 2012. Os participantes positivos para HLA-A*31 tiveram risco aumentado de desenvolver sepse (OR: 2,36 IC95%: 1,26-5,35). Não foi identificada outra associação significativa, quando considerado como nível de significância o valor de p<0,01. Conclusão: A expressão de HLA-A*31 está associada ao risco de desenvolvimento de sepse. .

Objective: The HLA haplotype has been associated with many autoimmune diseases, but no associations have been described in sepsis. This study aims to investigate the HLA system as a possible marker of genetic sepsis susceptibility. Methods: This is a prospective cohort study including patients admitted to an intensive care unit and healthy controls from a list of renal transplant donors. Patients with less 18 years of age; pregnant or HIV positive patients; those with metastatic malignancies or receiving chemotherapy; or with advanced liver disease; or with end-of-life conditions were excluded. The DNA was extracted from the whole blood and HLA haplotypes determined using MiliPlex® technology. Results: From October 2010 to October 2012, 1,121 patients were included (1,078 kidney donors, 20 patients admitted with severe sepsis and 23 with septic shock). HLA-A*31 positive subjects had increased risk of developing sepsis (OR 2.36, 95%CI 1.26-5.35). Considering a p value <0.01, no other significant association was identified. Conclusion: HLA-A*31 expression is associated to risk of developing sepsis. .

Prediction of sepsis-related outcomes in neonates through systematic genotyping of polymorphisms in genes for innate immunity and inflammation: a narrative review and critical perspective / Previsao de desfechos relacionados a sepse em neonatos atraves da genotipagem sistematica de polimorfismos de genes da imunidade inata e inflamacao: uma revisao narrativa e perspectiva critica

CONTEXT AND OBJECTIVE: Neonatal sepsis is associated with premature birth and maternal infection. Large-scale studies seek to define markers that identify neonates at risk of developing sepsis. Here, we examine whether the scientific evidence supports systematic use of polymorphism genotyping in cytokine and innate immunity genes, to identify neonates at increased risk of sepsis. DESIGN AND SETTING: Narrative literature review conducted at Fernandes Figueira Institute, Brazil. METHODS: The literature was searched in PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) and Cochrane Library. From > 400,000 references, 548 were retrieved based on inclusion/exclusion criteria; 22 were selected for detailed analysis after quality assessment. RESULTS: The studies retrieved addressed the impact of gene polymorphisms relating to immune mechanisms (most often TNF-a, LT-a, IL-6, IL-1β, IL-1ra, L-selectin, CD14 and MBL) or inflammatory mechanisms (ACE and angiotensin II receptors; secretory PLA2; and hemostatic factors). Despite initial reports suggesting positive associations between specific polymorphisms and increased risk of sepsis, the accumulated evidence has not confirmed that any of them have predictive power to justify systematic genotyping. CONCLUSIONS: Sepsis prediction through systematic genotyping needs to be reevaluated, based on studies that demonstrate the functional impact of gene polymorphisms and epidemiological differences among ethnically distinct populations. .

CONTEXTO E OBJETIVO: A sepse neonatal está associada ao parto prematuro e à infecção materna. Estudos em grande escala buscam marcadores que identifiquem neonatos em risco de desenvolver sepse. Examinamos aqui se a evidência científica apoia o uso sistemático de genotipagem dos polimorfismos em genes de citocinas e imunidade inata, para identificar neonatos com risco elevado de sepse. TIPO DE ESTUDO E LOCAL: Revis ão narrativa da literatura, Instituto Fernandes Figueira, Brasil. M ÉTODOS: Busca online da literatura foi feita no PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) e Cochrane Library. De mais de 400.000 referências, 548 foram recuperadas com base nos critérios de inclusão/exclusão, e 22, selecionadas para análise detalhada após verificação da qualidade. RESULTADOS: Recuperamos estudos de impacto dos polimorfismos em genes relacionados com mecanismos imunes (mais frequentemente, TNF-a, LT-a, IL-6, IL-1 β, IL-1ra, L-selectin, CD14, e MBL) ou inflamatórios (ACE e receptores de angiotensina II; PLA2 secretória; fatores hemostáticos). Contrariando estudos que inicialmente sugeriram associação positiva entre polimorfismos específicos e risco aumentado de sepse, a evidência acumulada não confirmou, para qualquer deles, valor preditivo que justifique genotipagem sistemática para orientar antibioticoterapia. CONCLUSÕES: A previsão da sepse por meio de genotipagem sistemática precisa ser reavaliada, com base em estudos que demonstram o impacto funcional de polimorfismos gênicos e as diferenças epidemiológicas entre populações etnicamente distintas. .

Estudo de associação genética entre fator de necrose tumoral alfa e sepse e choque séptico em pacientes pediátricos tailandeses / Genetic association study of tumor necrosis factor-alpha with sepsis and septic shock in Thai pediatric patients

OBJETIVOS: Avaliar a associação entre o polimorfismo genético do fator de necrose tumoral alfa (TNF-α) e o desenvolvimento de sepse e choque séptico em pacientes pediátricos tailandeses e investigar o impacto clínico de polimorfismos do TNF-α nessa população. MÉTODOS: Para a realização deste estudo de associação genética, foram analisados prospectivamente pacientes pediátricos (idade < 18 anos) com sepse clínica/choque séptico. Todos os dados foram coletados por especialistas em terapia intensiva pediátrica e as análises genéticas foram realizadas em um laboratório central. Um polimorfismo de nucleotídeo único [single nucleotide polymorphism (SNP)], localizado na região promotora 5' na posição -308, foi genotipado e os resultados foram associados a fenótipos clínicos. RESULTADOS: Foram investigados 167 indivíduos tailandeses, dos quais 66 eram pacientes pediátricos com sepse/choque séptico e 101 eram controles saudáveis. Curiosamente, não foi possível identificar associação entre sepse e o polimorfismo -308 (G→A), um dos principais SNPs anteriormente associado à sepse em várias populações caucasianas, visto que não houve diferença de frequência entre casos e controles. CONCLUSÕES: Neste estudo, o principal polimorfismo do TNF-α -308 não esteve associado à sepse clínica/choque séptico na população tailandesa. Essa informação é importante para futuras análises que busquem identificar a função do TNF-α como risco genético para o desenvolvimento de imunopatologia subjacente a várias doenças no continente asiático.

OBJECTIVES: To evaluate the association between the genetic polymorphism of the tumor necrosis factor-alpha (TNF-α) gene and the development of sepsis and septic shock in Thai pediatric patients and to investigate the clinical impacts of TNF-α polymorphisms in this population. METHODS: To perform this genetic association study, a prospective analysis of pediatric patients (age < 18 years) with clinical sepsis/septic shock was conducted. All clinical data were collected by pediatric intensive care experts, and genetic analyses were performed at a central laboratory. A single nucleotide polymorphism (SNP) located in the 5'-promoter region at position -308 was genotyped and the results were associated with clinical phenotypes. RESULTS: A total of 167 Thai individuals were investigated, 66 of which were pediatric patients with sepsis/septic shock and 101 were healthy controls. Interestingly, we could not identify an association between sepsis and -308 (G→A) polymorphism, which have previously been demonstrated to be a major SNP associated with sepsis in several Caucasian populations, since there was no frequency difference between cases and controls. CONCLUSIONS: In this report, the major TNF-α polymorphism (-308) was not associated with clinical sepsis/septic shock in Thais. This information will be important for future analyses to identify the role of TNF-α as a genetic risk for the development of immunopathology underlying several diseases in Asia.

Atualidades proteômicas na sepse / Proteomic updates on sepsis

A ampliação do conhecimento das técnicas de análise proteômica tem permitido maior compreensão das bases moleculares relacionadas à identificação de vias de sinalização celular, de proteínas modificadoras, de modificações pós-traducionais, além de caracterizar marcadores biológicos específicos. Desta feita, a documentação de determinadas proteínas expressas na sepse constitui uma promissora abordagem para elucidação dos aspectos fisiopatológicos, diagnósticos, terapêuticos e prognósticos dessa condição, com a finalidade de aplicação na prática clínica. Embora os resultados sejam ainda preliminares, a proteômica poderá oferecer bons subsídios para o melhor manejo dos pacientes sépticos. Dessa feita, o objetivo do presente artigo é apresentar uma breve revisão das aplicações dos estudos proteômicos na sepse.

The increased knowledge regarding proteomic analysis techniques has allowed for better understanding of the molecular bases related to the identification of cell signaling, modifying protein, and post-translational modification pathways, in addition to the characterization of specific biological markers. Thus, documenting certain proteins expressed in sepsis is a promising approach to elucidate pathophysiological, diagnostic, therapeutic, and prognostic aspects in this condition with a purpose of applying them to clinical practice. Although the studies are still preliminary, proteomics may offer good benefits for the better management of septic patients. Thus, this article aims to introduce a short review of the applications of proteomic studies to sepsis.

Sepsis: la otra cara de la respuesta inmune / Sepsis: the other face of immune response

La sepsis continúa siendo una de las principales causas de muerte alrededor del mundo a pesar de los grandes avances en su investigación. Representa un desequilibrio en los diferentes mecanismos inmunológicos responsables de neutralizar la invasión de un agente infeccioso. En este artículo se presenta una revisión sobre los conceptos fisiopatológicos de la sepsis, así como sobre las diferentes alteraciones genéticas que hacen a un individuo susceptible a desarrollarla.

Worldwide, sepsis continues to be a major cause of death, in spite of the impressive advances in its research. This condition represents an imbalance in the different immunological mechanisms responsible for neutralizing the infectious agent invasion. In this paper, a review of the physiopathological concepts of sepsis is presented, including the different genetic variations which make an individual susceptible to sepsis.

TNF -308G > a promoter polymorphism (rs1800629) and outcome from critical illness

BACKGROUND: The susceptibility to adverse outcome from critical illness (occurrence of sepsis, septic shock, organ dysfunction/failure, and mortality) varies dramatically due to different degrees of inflammatory response. An over expression of tumor necrosis factor alpha (TNF-α) can lead to the progression of the inflammatory condition. OBJECTIVE: We assessed the relationship of the genotype distribution of -308G >A TNF-α polymorphism with regard to the development of sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients. METHODS: Observational, hospital-based cohort study of 520 critically ill Caucasian patients from southern Brazil admitted to the general ICU of São Lucas Hospital, Porto Alegre, Brazil. Patients were monitored daily from the ICU admission day to hospital discharge or death, measuring SOFA score, sepsis, and septic shock occurrences. The -308G >A TNF-α SNP effect was analyzed in the entire patient group, in patients with sepsis (349/520), and in those who developed septic shock (248/520). RESULTS: The genotypic and allelic frequencies were -308GG = 0.72; -308GA = 0.27; -308AA = 0.01; -308G = 0.85; -308A = 0.15. No associations were found with sepsis, septic shock, organ dysfunction, and/or mortality rates among the TNF-α genotypes. Our results reveal that the -308G >A TNF-α SNP alone was not predictive of severe outcomes in critically ill patients. CONCLUSION: The principal novel input of this study was the larger sample size in an investigation with -308G > A TNF-α SNP. The presence of -308A allele is not associated with sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients.

Comet assay in neonatal sepsis.

Objective. To determine whether the DNA damage detected using the Comet assay helps in the diagnosis of neonatal sepsis Methods. Sepsis was diagnosed, based on clinical findings, laboratory findings and positive culture results, in 24 of the 48 newborns who participated in the study. Hematological parameters, baseline demographic data and genotoxic evaluation were investigated. Results. There were no significant differences in hematological, demographic and genotoxic data between cases and controls. Conclusions. The Comet assay proved to be ineffective in the diagnosis of neonatal sepsis.