Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway

Chu, Chien‐Ming; Chiu, Li-Chung; Yu, Chih-Teng; Chuang, Li‐Pang; Kao, Kuo‐Chin; Li, Lifu; Wu, Huang-Pin

doi:10.1155/2021/2255017

Cited by 7 publications

(5 citation statements)

References 27 publications

(22 reference statements)

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“…Although all three types of cell death have been studies in sepsis, their communication pathways at the molecular level are largely unknown. Moreover, cell death mediated by apoptosis often occurs in heart, kidney, and other organ failures during sepsis ( 6 ) pyroptosis is more commonly associated with lethal sepsis ( 4 , 7 , 8 ). Necroptosis has also been observed in kidney damage resulting from mitochondrial dysfunction in sepsis ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis

Dai,

Zheng,

et al. 2024

Front. Immunol.

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BackgroundThe poor prognosis of sepsis warrants the investigation of biomarkers for predicting the outcome. Several studies have indicated that PANoptosis exerts a critical role in tumor initiation and development. Nevertheless, the role of PANoptosis in sepsis has not been fully elucidated.MethodsWe obtained Sepsis samples and scRNA-seq data from the GEO database. PANoptosis-related genes were subjected to consensus clustering and functional enrichment analysis, followed by identification of differentially expressed genes and calculation of the PANoptosis score. A PANoptosis-based prognostic model was developed. In vitro experiments were performed to verify distinct PANoptosis-related genes. An external scRNA-seq dataset was used to verify cellular localization.ResultsUnsupervised clustering analysis using 16 PANoptosis-related genes identified three subtypes of sepsis. Kaplan-Meier analysis showed significant differences in patient survival among the subtypes, with different immune infiltration levels. Differential analysis of the subtypes identified 48 DEGs. Boruta algorithm PCA analysis identified 16 DEGs as PANoptosis-related signature genes. We developed PANscore based on these signature genes, which can distinguish different PANoptosis and clinical characteristics and may serve as a potential biomarker. Single-cell sequencing analysis identified six cell types, with high PANscore clustering relatively in B cells, and low PANscore in CD16+ and CD14+ monocytes and Megakaryocyte progenitors. ZBP1, XAF1, IFI44L, SOCS1, and PARP14 were relatively higher in cells with high PANscore.ConclusionWe developed a machine learning based Boruta algorithm for profiling PANoptosis related subgroups with in predicting survival and clinical features in the sepsis.

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Section: Introductionmentioning

confidence: 99%

Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis

Dai,

Zheng,

et al. 2024

Front. Immunol.

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“…One prominent aspect of immunosuppression observed in experimental sepsis was lymphocyte apoptosis. This process further contributed to immunosuppression, making the host more vulnerable to invading pathogens [45][46][47]. Sepsis patients often experienced a signi cant decrease in lymphocyte count, which can be attributed to lymphocyte marginalization, increased apoptosis, and cell redistribution [48].…”

Section: Discussionmentioning

confidence: 99%

The value of Lymphocyte-to-C-Reactive Protein Ratio for predicting clinical outcomes in patients with sepsis in intensive care unit: a retrospective single-center study

song,

hu,

zhang

2024

Preprint

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Background The lymphocyte-to-C-reactive protein ratio (LCR) was a novel biomarker of inflammation that had been implicated in various diseases. Nevertheless, the role of LCR in the context of sepsis patients admitted to the Intensive Care Unit (ICU) had not been thoroughly elucidated. This study aimed to determine the significance of the LCR in predicting the prognosis of sepsis patients within ICU. Methods A sample of sepsis patients requiring ICU care was selected from the Affiliated Hospital of Jiangsu University. These patients were then segmented into four quartiles based on their LCR levels. The primary endpoint of the study was 30-day mortality and the secondary endpoint was the occurrence of Acute Kidney Injury (AKI). Survival analysis, via the Kaplan-Meier method and log-rank test, was conducted to assess survival rates. Cox proportional hazards regression and logistic regression models were employed to investigate the association between LCR and clinical outcomes. Additional subgroup analyses were conducted to evaluate the influence of other confounding factors on the relationship between LCR and patient outcomes. Results A total of 1123 patients were enrolled in this study, with a median age of 75 (65–84) years, and 707 (63.0%) of them were male. The 30-day mortality rate was 28.1%, while the incidence of AKI was 45.6%. A progressive decrease in LCR levels was found to be associated with an increased cumulative incidence of 30-day mortality (log-rank P < 0.001). Multivariable Cox proportional hazards analyses demonstrated that LCR was an independent predictor of 30-day mortality [per 1-unit increase in LCR: HR (95%CI): 0.370 (0.142–0.963); P = 0.042]. Additionally, multivariable logistic regression analysis revealed a significant association between LCR and AKI occurrence [per 1-unit increase in LCR: OR (95%CI): 0.541 (0.307–0.953); P = 0.034]. Furthermore, subgroup analysis indicated a stronger correlation for patients aged over 65 years compared to those aged 65 or younger (p for interaction < 0.05) in predicting 30-day mortality or AKI occurrence based on LCR. Conclusions A reduction in LCR was notably linked to 30-day mortality and the occurrence of AKI in sepsis patients. These findings suggested that LCR could potentially serve as a valuable tool in identifying sepsis patients at a heightened risk of adverse outcomes.

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“…An essential stage in the onset of experimental sepsis has been identified as lymphocyte apoptosis. This process can further induce a state of immunosuppression, which increases host susceptibility to invading pathogens [ 8 , 25 , 26 ]. Meanwhile, several studies reported that peripheral blood lymphocyte count decreased in patients with sepsis, and lymphopenia was associated with poor outcomes [ 10 , 27 – 29 ].…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte-to-C-Reactive Protein Ratio as an Early Sepsis Biomarker for Neonates with Suspected Sepsis

Wei

et al. 2023

Mediators of Inflammation

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Background. Neonatal sepsis is an extremely dangerous and fatal disease among neonates, and its timely diagnosis is critical to treatment. This research is aimed at evaluating the clinical significance of the lymphocyte-to-C-reactive protein ratio (LCR) as an early sepsis indicator in neonates with suspected sepsis. Methods. Between January 2016 and December 2021, 1269 neonates suspected of developing sepsis were included in this research. Among them, sepsis was diagnosed in 819 neonates, with 448 severe cases, as per the International Pediatric Sepsis Consensus. Data related to clinical and laboratory tests were obtained via electronic medical records. LCR was calculated as total lymphocyte (109 cells/L)/C-reactive protein (mg/L). Multivariate logistic regression analysis was employed to evaluate the effectiveness of LCR as an independent indicator for determining sepsis in susceptible sepsis neonates. Receiver operating characteristic (ROC) curve analysis was conducted for investigating the diagnostic significance of LCR in sepsis. When suitable, the statistical tool SPSS 24.0 was used for statistical analyses. Results. LCR decreased significantly in the control, mild, and severe sepsis groups. Further analyses exhibited that there was a substantially greater incidence of sepsis in neonates in the low-LCR group ( LCR ≤ 3.94 ) as opposed to the higher LCR group ( LCR > 3.94 ) (77.6% vs. 51.4%, p < 0.001 ). Correlation analysis indicated a substantial negative association of LCR with procalcitonin ( r = − 0.519 , p < 0.001 ) and hospital stay duration ( r = − 0.258 , p < 0.001 ). Multiple logistic regression analysis depicted LCR as an independent indicator for identifying sepsis and severe cases of this disease. ROC curve analysis indicated the optimal cutoff value of LCR in identifying sepsis to be 2.10, with 88% sensitivity and 55% specificity. Conclusions. LCR has proven to be a potentially strong biomarker capable of identifying sepsis in a timely manner in neonates suspected to have the disease.

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Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway

Cited by 7 publications

References 27 publications

Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis

Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis

The value of Lymphocyte-to-C-Reactive Protein Ratio for predicting clinical outcomes in patients with sepsis in intensive care unit: a retrospective single-center study

Lymphocyte-to-C-Reactive Protein Ratio as an Early Sepsis Biomarker for Neonates with Suspected Sepsis

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