Silencing Cardiac Troponin I‐Interacting Kinase Reduces Lipopolysaccharide‐Induced Sepsis‐Induced Myocardial Dysfunction in Rat by Regulating Apoptosis‐Related Proteins

Yang, Dong; Jiang, Yanzhou; Qian, Hai-xia; Liu, Xiaomin; Mi, Liguo

doi:10.1155/2021/5520051

“…In the general hospital population suspected of infection, when SOFA score is more than 2, the in-hospital mortality rate can exceed 10%. Even if the patient showed mild dysfunction, it may further worsen [ 35 ]. David and other studies found that the SOFA score of children with sepsis with long hospitalization days was remarkably higher compared to children with short hospitalization days.…”

Section: Discussionmentioning

confidence: 99%

Evaluation Value and Clinical Significance of Cardiac Troponin Level and Pediatric Sequential Organ Failure Score in the Definition of Sepsis 3.0 in Critically Ill Children

Wu

¹

,

Shen²,

Wang

³

et al. 2022

Computational and Mathematical Methods in Medicine

2

0

1

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Objective. A case-control study was conducted to explore the value and clinical significance of troponin level and pediatric sequential organ failure score in the evaluation of sepsis 3.0 definition in critically ill children. Methods. 180 children with sepsis who were admitted to the ICU from March 2019 to June 2021 were enrolled in our hospital as the research objects. In addition, 100 children with general infection did not meet the diagnostic criteria of systemic inflammatory response syndrome (SIRS) as controls. The creatine kinase MB (CK-MB) and cardiac troponin I (cTnI) data at the 1st and 24-72 h after admission to pediatric intensive care unit (PICU) were enrolled as the observation indexes of myocardial enzymology. In the meantime, the relevant literature was reviewed to obtain the indicators related to sepsis death. The data of the first examination in the medical history data were enrolled for analysis. According to the definition of sepsis 3.0 in critically ill children, they were assigned into sepsis and nonsepsis group. According to the survival outcome of discharge and 30 days after discharge, the patients were assigned into the death subgroup and survival subgroup and were assigned into the sequential organ failure assessment SOFA score ≥ 2 subgroup and< 2 subgroup according to SOFA score. COX proportional hazard regression was used to analyze the relationship between CK-MB, cTnI, and SOFA scores and prognosis. ROC curve was adopted to analyze the value of CK-MB, cTnI, and SOFA scores in the evaluation of critical sepsis in children. Results. Univariate analysis indicated that the prognosis of children with sepsis was correlated with abnormal levels of CK-MB and cTnI, SOFA score, oxygenation index < 200 , mean arterial pressure, and Glasgow coma scale (GCS), and the difference was statistically significant ( P < 0.05 ). The results of COX regression analysis indicated that the variables that were remarkably associated with death from sepsis in children were CK-MB, elevated cTnI levels, and SOFA score ≥ 2 , and serum cTnI and/or CK-MB levels and SOFA score were remarkably higher correlation ( r = 0.453 , P < 0.05 ). In terms of the myocardial enzyme levels in the sepsis group and the nonsepsis group, the levels of CK-MB and (or) cTnI augmented in 121/180 cases (67.22%) in the sepsis group and in 19/100 cases (19.00%) in the nonsepsis group. The levels of CK-MB and (or) cTnI were augmented, and the difference was statistically significant ( P < 0.05 ). The levels of CK-MB and cTnI in the sepsis group at admission to ICU and 24 to 72 hours after admission were remarkably higher compared to the nonsepsis group. The levels of CK-MB and cTnI at 24-72 h were higher compared to ICU. The myocardial enzyme levels of different SOFA scores and survival outcome subgroups in the sepsis group were compared. The subgroup with SFOA score ≥ 2 points had remarkably higher levels of CK-MB and (or) cTnI than the subgroup with <2 points. The survival subgroup of CK-MB and cTnI level was remarkably higher compared to the death subgroup, the CK-MB and cTnI levels in each subgroup at 224-72 hours were remarkably higher compared to the ICU, and the difference was statistically significant ( P < 0.05 ). Kaplan-Meier method and log-rank test indicated that the survival rates of groups 1 to 4 at 30 days were 33.23%, 78.71%, 40.03%, and 100.00%, respectively. The average survival time and their 95% CI were 12.82 d (10.52~ 16.26 d), 22.34 d (18.76~ 25.81 d), 14.65 d (11.62~ 16.38 d), and 30 d (30.00~ 30.00 d), respectively. Pairwise comparison indicated that the survival time of children in group 1 was the shortest, and that in group 4 was the longest. The results of ROC curve research showed that the CK-MB, cTnI, and SOFA scores and AUC for the combination test were 0.778 (95% CI 0.642–0.914), 0.736 (95% CI 0.602–0.890), 0.848 (95% CI 0.733–0.963), and 0.934 (95% CI 0.854–0.999), respectively. The AUC of combined diagnosis was remarkably higher compared to single factor prediction, and the difference was statistically significant ( P < 0.05 ). Predictive value showed the joint test > SOFA score > CK − MB > cTnI . Conclusion. Troponin level and pediatric SOFA score can be adopted as effective indicators to assess the severity and prognosis of patients with sepsis and can guide the formulation of a reasonable treatment plan.

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“…erefore, this research indicated that sepsis is not only accompanied by inflammation but also extensive apoptosis, which could induce LDH release due to structural damage to the affected cells [21]. Similarly, the relative levels of Bax, a proapoptotic protein that can release apoptosis-promoting substances into the cytoplasm [22], and Bcl2, an antiapoptotic protein that blocks oligomerization of proapoptotic proteins [23], suggested that sepsis is correlated with increased apoptosis. In addition, we also investigated the expression and activation of caspase-3, and the vital terminal splicing enzyme in the process of apoptosis is one of the executors of apoptosis [24].…”

Section: Discussionmentioning

confidence: 83%

Electroacupuncture at Zusanli Alleviates Sepsis by Regulating the TLR4-MyD88-NF-Kappa B Pathway and Diversity of Intestinal Flora

Zhan

¹

,

Líu

²

,

Zheng

³

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Electroacupuncture (EA) at the Zusanli acupoint (ST36) has shown therapeutic potential for sepsis due to its ability to limit inflammation and to regulate gastrointestinal tract symptoms. However, the mechanisms contributing to the effects of EA at ST36 on sepsis and connections with the intestinal flora remain unclear. This study was designed to explore the effects of EA at ST36 on Toll-like receptor 4 signaling and the intestinal flora. Methods. ICR mice were randomly divided into 4 groups: control group, model group, EA group, and sham EA group. EA at ST36 was performed at 2.5 mA and 2 to 100 Hz, and the 30 min of dense wave was achieved over 5 days. A sepsis model was built by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/mL). The levels of expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and IL-10 were detected by enzyme-linked immunosorbent assays, and lactate dehydrogenase (LDH) levels in serum were measured by biochemical tests. Expression levels of Bax, Bcl2, cleaved caspase-3, Toll-like receptor (TLR4), nuclear factor-kappa B (NF-κB), and myeloid differentiation factor 88 (MyD88) were assessed by the Western blotting. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to evaluate apoptosis. The intestinal microecology was assessed via 16S rRNA gene sequencing. Results. EA at ST36 reduced the expression of IL-1β, IL-6, and TNF-α and increased the expression of IL-10 to inhibit the inflammatory response. EA at ST36 also inhibited apoptosis, as measured by TUNEL staining, and decreased the Bax/Bcl2 ratio and levels of caspase-3 and cleaved caspase-3, as well as LDH release. Our results suggest that alleviation of sepsis may correlate with the downregulation of levels of TLR4, NF-κB, and MyD88. Importantly, EA at ST36 improved the diversity of the intestinal flora and increased the abundance of Firmicutes and Actinobacteria. Conclusion. EA at ST36 prevented sepsis from worsening by inhibiting inflammation and apoptosis, which correlated with the regulation of the TLR4/NF-κB/MyD88 signaling axis and modulation of the intestinal flora.

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“…Yang et al reported that the inhibition of pro-apoptotic protein Bax could alleviate the injury of H9C2 cells induced by LPS. 37 Sun et al also found that the release of inflammatory cytokines by activated astrocytes can exacerbate sepsis-associated encephalopathy. 13 Recent research has implicated that ferroptosis is distinct from apoptosis and pyroptosis, which is involved in developing sepsis.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Dexmedetomidine on Sepsis-Induced Vascular Leakage by Alleviating Ferroptosis via Regulating Metabolic Reprogramming

She¹,

Hu²,

Zhou³

et al. 2021

JIR

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Introduction Vascular leakage plays a vital role in sepsis-induced multi-organ dysfunction. Currently, no specific measures are available for vascular leakage. Ferroptosis, as a recently recognized form of cell death, plays a crucial role in cell dysfunction. It is still unknown whether ferroptosis participates in the occurrence of organ dysfunction following sepsis. Our previous study showed that dexmedetomidine (Dex) could alleviate sepsis-induced organ dysfunction. However, whether the mechanism is related to ferroptosis is not clear. Methods The publicly available datasets of septic patients were reanalyzed, and septic models in vivo and vitro by cecal ligation and puncture and lipopolysaccharide-stimulated vascular endothelial cells (VECs) were applied. The occurrence of ferroptosis in septic patients and rats was observed, and the protective effects of Dex on ferroptosis, and related mechanisms on regulating metabolic reprogramming and mitochondrial fission were further studied. Results The transcriptomics data of patients from the GEO database showed that ferroptosis was closely related to sepsis. Sepsis induced significant ferroptosis in VECs by metabolomics analysis. The level of lipid peroxidation was increased in VECs, and the mitochondrial cristae was decreased after sepsis. Metabolomics analysis showed that Dex activated the pentose phosphate pathway and increased glutathione in VECs via up-regulation of G6PD expression. Dex could antagonize sepsis-induced the decrease in the level of Nrf2. The Nrf2 inhibitor reversed the protective effect of Dex on ferroptosis. Further study showed that Dex significantly alleviated sepsis-induced mitochondrial over-division, improved mitochondrial function, and decreased ROS, further inhibiting the ferroptosis of VECs. Dex alleviated the permeability of vessels by reducing ferroptosis and enhanced the intercellular junction of VECs. Conclusion Dex protects vascular leakage following sepsis by inhibiting ferroptosis. The mechanism is mainly related to metabolic reprogramming via Nrf2 up-regulation and inhibition of mitochondrial fission.

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Silencing Cardiac Troponin I‐Interacting Kinase Reduces Lipopolysaccharide‐Induced Sepsis‐Induced Myocardial Dysfunction in Rat by Regulating Apoptosis‐Related Proteins

Cited by 9 publications

References 27 publications

Evaluation Value and Clinical Significance of Cardiac Troponin Level and Pediatric Sequential Organ Failure Score in the Definition of Sepsis 3.0 in Critically Ill Children

Evaluation Value and Clinical Significance of Cardiac Troponin Level and Pediatric Sequential Organ Failure Score in the Definition of Sepsis 3.0 in Critically Ill Children

Electroacupuncture at Zusanli Alleviates Sepsis by Regulating the TLR4-MyD88-NF-Kappa B Pathway and Diversity of Intestinal Flora

Protective Effects of Dexmedetomidine on Sepsis-Induced Vascular Leakage by Alleviating Ferroptosis via Regulating Metabolic Reprogramming

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