Infection-induced innate antimicrobial response disorders: from signaling pathways and their modulation to selected biomarkers

Stelmasiak, Marta; Słotwiński, Robert

doi:10.5114/ceji.2020.94712

Cited by 5 publications

(4 citation statements)

References 121 publications

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“…10 The possible mechanisms of SIRS include: a pro-inflammatory response of inflammatory cytokines; an increased release of toxic substances such as excitatory amino acids, nitric oxide and free radicals; and an increased production of thrombin, which induces glial in neuronal apoptosis of cells. 11,29,30 Previous studies focused on the association between SIRS and the outcomes after ICH. Boehme et al 12 found that patients with SIRS were at an increased risk of poor prognosis, but SIRS was not an independent predictor of poor functional outcomes after ICH.…”

Section: The Logistic Regression Analysis Was Performed To Analyzementioning

confidence: 99%

Association between systemic inflammatory response syndrome and hematoma expansion in intracerebral hemorrhage

Zhu¹,

Xie²,

Shen³

et al. 2022

Adv Clin Exp Med

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Background. Hematoma expansion (HE) is a relatively common complication after intracerebral hemorrhage.Objectives. To explore the association between systemic inflammatory response syndrome (SIRS) and HE in patients with intracerebral hemorrhage (ICH). Materials and methods.From June 2013 to October 2020, the sociodemographic data and clinical data of 780 ICH patients were collected. The logistic regression analysis with odd ratios (ORs) and 95% confidence intervals (95% CIs) was performed to analyze the risk factors for HE in patients with ICH.Results. Hematoma expansion occurred in 151 (19.36%) patients with ICH. Significant differences were presented between SIRS and HE (OR = 2.549, 95% CI: [1.497; 4.342], p = 0.0006). After adjusting the covariates, a further analysis showed that the respiratory rate >20 beats/min (OR = 3.436, 95% CI: [1.981; 5.960], p < 0.0001), white blood cell (WBC) > 12×10 9 /L or WBC ≤ 4×10 9 /L (OR = 2.489, 95% CI: [1.494; 4. 149], p = 0.0005) increased the risk for HE in ICH patients. Our study also found that the significant differences between HE and non-HE patients in proportion of patients with history of diabetes mellitus, basal ganglia hemorrhage, hypothalamus hemorrhage and fasting blood glucose (all p < 0.05) (OR = 2.076, 95% CI: [1.274; 3.381], p = 0.0034), basal ganglia hemorrhage (OR = 2.512, 95% CI: [1.496; 4.218], p = 0.0005), hypothalamus hemorrhage (OR = 2. 121, 95% CI: [1.007; 4.466], p = 0.0479), high C-reactive protein (CRP) (OR = 1.013, 95% CI: [1.002; 1.024], p = 0.0184), and hyperglycemia (OR = 1.099, 95% CI: [1.026; 1. 178], p = 0.0074) were associated with an increased risk of HE in ICH patients. Conclusions.The SIRS is closely associated with the risk of HE. Respiratory rate >20 beats/min and WBC count >12(10 9 /L) or ≤4(10 9 /L) increased the risk for HE in ICH patients. These findings can help to achieve the early prevention of HE and improve the prognosis of ICH patients.

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Section: The Logistic Regression Analysis Was Performed To Analyzementioning

confidence: 99%

Association between systemic inflammatory response syndrome and hematoma expansion in intracerebral hemorrhage

Zhu¹,

Xie²,

Shen³

et al. 2022

Adv Clin Exp Med

View full text Add to dashboard Cite

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“…Based on the bench-experiments of multiplex immunoassay and flow cytometry analysis in deficient mice, the cytokine production, neutrophil migration, and phagocytic function have been suggested to play critical roles in the pathogenesis of sepsis ( 21 – 23 ). Cytokines and chemokines including IL-6 ( 24 ), IL-10 ( 7 , 24 ), CD14 ( 17 ), to name a few, were suggested as potential biomarkers for early diagnosis (before organ dysfunction occurs) of sepsis ( 25 ). But due to evolutionary discordance between human and mouse innate immune signaling ( 26 ), these may not necessarily be true biomarkers ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

CASP-Model Sepsis Triggers Systemic Innate Immune Responses Revealed by the Systems-Level Signaling Pathways

Meng

et al. 2022

Front. Immunol.

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Colon ascendens stent peritonitis (CASP) surgery induces a leakage of intestinal contents which may cause polymicrobial sepsis related to post-operative failure of remote multi-organs (including kidney, liver, lung and heart) and possible death from systemic syndromes. Mechanisms underlying such phenomena remain unclear. This article aims to elucidate the mechanisms underlying the CASP-model sepsis by analyzing real-world GEO data (GSE24327_A, B and C) generated from mice spleen 12 hours after a CASP-surgery in septic MyD88-deficient and wildtype mice, compared with untreated wildtype mice. Firstly, we identify and characterize 21 KO MyD88-associated signaling pathways, on which true key regulators (including ligands, receptors, adaptors, transducers, transcriptional factors and cytokines) are marked, which were coordinately, significantly, and differentially expressed at the systems-level, thus providing massive potential biomarkers that warrant experimental validations in the future. Secondly, we observe the full range of polymicrobial (viral, bacterial, and parasitic) sepsis triggered by the CASP-surgery by comparing the coordinated up- or down-regulations of true regulators among the experimental treatments born by the three data under study. Finally, we discuss the observed phenomena of “systemic syndrome”, “cytokine storm” and “KO MyD88 attenuation”, as well as the proposed hypothesis of “spleen-mediated immune-cell infiltration”. Together, our results provide novel insights into a better understanding of innate immune responses triggered by the CASP-model sepsis in both wildtype and MyD88-deficient mice at the systems-level in a broader vision. This may serve as a model for humans and ultimately guide formulating the research paradigms and composite strategies for the early diagnosis and prevention of sepsis.

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“…MicroRNAs (miRNAs), a type of ncRNAs, are short, single-stranded RNA fragments of 21-23 bases that contribute to the maintenance of homeostasis, regulation of cellular physiological functions, the cell cycle, differentiation, and apoptosis. miRNAs have been implicated to affect in ammatory and antiin ammatory immune responses, such as sepsis, diabetes, tumors, chronic obstructive pulmonary disease, asthma, in ammatory bowel disease, and schizophrenia [12].…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of messenger RNA and microRNA in patients with community- acquired pneumonia-associated sepsis

Oda

Matsumoto

Togami

et al. 2023

Preprint

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Background: Community-acquired pneumonia (CAP) is defined as an acute lung infection involving the alveoli that occurs in a patient without recent health care exposure. A complication of CAP is severe sepsis, a syndrome of infection often accompanied by systemic inflammation and organ dysfunction. The aim of this study was to evaluate mRNA and miRNA in whole blood and to perform an integrative analysis to assess cellular signals that play a role in the pathogenesis of patients with CAP-associated sepsis. Methods: This was a prospective, observational, single-center study of patients transported to the Department of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University. Patients with CAP-associated sepsis were analyzed. The diagnosis of pneumonia was made according to the clinical findings, including blood samples and chest computed tomography scan, and the diagnosis of sepsis followed the Sepsis-3 guidelines. Results: We included 14 critically ill patients with CAP-associated sepsis and 15 healthy control subjects (HCS). The median ages of the patient group and HCS were 78 and 55 years, and their body mass indexes were 22.8 and 21.7 kg/m2, respectively. All patients were treated at the critical care center, and 11 of the 14 patients received ventilatory management. All patients survived. These 14 patients met the diagnostic criteria of Sepsis-3 and were diagnosed as having CAP-associated sepsis. Of them, 6 patients met the diagnostic criteria for septic shock. RNA sequencing showed the number of genes with up:down (upregulated:downregulated) expression variation (false discovery rate [FDR] <0.05, |log2 fold change| >1.2) to be 1209:1461 for mRNA; 51:21 for microRNA; and 646:1274 for miRNA-targeted mRNA. Canonical pathway analysis using mRNA showed activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathways and inhibition of the Th1 signaling pathway as well as that using miRNA-targeted mRNAs. Conclusions: Using integrated analysis of mRNA and miRNA, we elucidated for the first time, to our knowledge, that T-cell exhaustion occurred during the acute phase of CAP-associated sepsis and that miRNA regulated Th1 signaling and PD-1 and PD-L1 cancer immunotherapy signaling through the RNA interference action of mRNA.

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Infection-induced innate antimicrobial response disorders: from signaling pathways and their modulation to selected biomarkers

Cited by 5 publications

References 121 publications

Association between systemic inflammatory response syndrome and hematoma expansion in intracerebral hemorrhage

Association between systemic inflammatory response syndrome and hematoma expansion in intracerebral hemorrhage

CASP-Model Sepsis Triggers Systemic Innate Immune Responses Revealed by the Systems-Level Signaling Pathways

Integrated analysis of messenger RNA and microRNA in patients with community- acquired pneumonia-associated sepsis

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