Breaking the bond between tetranectin and HMGB1 in sepsis

Paterson, Cameron W; Ford, Mandy L.; Coopersmith, Craig M.

doi:10.1126/scitranslmed.abb2575

Cited by 14 publications

(7 citation statements)

References 10 publications

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“…fully understood, although it has been implicated in multiple bone disorders and wound healing [46]. In this study, TN showed a protective effect against mortality.…”

Section: Plos Onementioning

confidence: 64%

Characterization of a proteomic profile associated with organ dysfunction and mortality of sepsis and septic shock

et al. 2022

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Introduction The search for new biomarkers that allow an early diagnosis in sepsis and predict its evolution has become a necessity in medicine. The objective of this study is to identify, through omics techniques, potential protein biomarkers that are expressed in patients with sepsis and their relationship with organ dysfunction and mortality. Methods Prospective, observational and single-center study that included adult patients (≥ 18 years) who were admitted to a tertiary hospital and who met the criteria for sepsis. A mass spectrometry-based approach was used to analyze the plasma proteins in the enrolled subjects. Subsequently, using recursive feature elimination classification and cross-validation with a vector classifier, an association of these proteins with mortality and organ dysfunction was established. The protein-protein interaction network was analyzed with String software. Results 141 patients were enrolled in this study. Mass spectrometry identified 177 proteins. Of all of them, and by recursive feature elimination, nine proteins (GPX3, APOB, ORM1, SERPINF1, LYZ, C8A, CD14, APOC3 and C1QC) were associated with organ dysfunction (SOFA > 6) with an accuracy of 0.82 ± 0.06, precision of 0.85 ± 0.093, sensitivity 0.81 ± 0.10, specificity 0.84 ± 0.10 and AUC 0.82 ± 0.06. Twenty-two proteins (CLU, LUM, APOL1, SAA1, CLEBC3B, C8A, ITIH4, KNG1, AGT, C7, SAA2, APOH, HRG, AFM, APOE, APOC1, C1S, SERPINC1, IGFALS, KLKB1, CFB and BTD) were associated with mortality with an accuracy of 0.86 ± 0.05, a precision of 0.91 ± 0.05, a sensitivity of 0.91 ± 0.05, a specificity of 0.72 ± 0.17, and an area under the curve (AUC) of 0.81 ± 0.08 with a confidence interval of 95%. Conclusion In sepsis there are proteomic patterns associated with organ dysfunction and mortality.

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“…fully understood, although it has been implicated in multiple bone disorders and wound healing [46]. In this study, TN showed a protective effect against mortality.…”

Section: Plos Onementioning

confidence: 64%

Characterization of a proteomic profile associated with organ dysfunction and mortality of sepsis and septic shock

et al. 2022

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“…[33,34] Studies showed that CLEC3B not only played an important role in tumorigenesis and metastasis but also in tissue remolding, neuroprotection, and inflammation. [35][36][37] CRTAC1, which belongs to the beta-propeller protein, is produced by chondrocytes and alveolar AT2 cells in the human body. [38] Yang et al claimed that CRTAC1 inhibited bladder cancer proliferation migration and invasion by inactivating the TGF-β pathway.…”

Section: Discussionmentioning

confidence: 99%

Identification of metabolism-related gene signature in lung adenocarcinoma

Wang,

Wang

2023

Medicine

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Aim: Lung cancer is one of the most common cancers in China and has a high mortality rate. Most patients who are diagnosed have lost the opportunity to undergo surgery. Aberrant metabolism is closely associated with tumorigenesis. We aimed to identify an effective metabolism-related prediction model for assessing prognosis based on the cancer genome atlas (TCGA) and GSE116959 databases. Methods: TCGA and GSE116959 datasets from Gene Expression Omnibus were used to obtain lung adenocarcinoma (LUAD) data. Additionally, we captured metabolism-related genes (MRGs) from the GeneCards database. First, we extracted differentially expressed genes using R to analyze the LUAD data. We then selected the same differentially expressed genes, including 168 downregulated and 77 upregulated genes. Finally, 218 differentially expressed MRGs (DEMRGs) were included to perform functional enrichment analysis and construct a protein–protein interaction network with the help of Cytoscape and Search Tool for the Retrieval of Interacting Genes database. Cytoscape was used to visualize the intensive intervals in the network. Then univariate and Least Absolute Shrinkage and Selection Operator Cox regression analyses, which assisted in identifying the overall survival (OS)-related DEMRGs and building a 10-DEMRG prognosis model, were performed. The prognostic values, tumor immunity relevance, and molecular mechanism were further investigated. A nomogram incorporating signature, age, gender, and TNM stage was established. Results: A 10-DEMRG model was established to forecast the OS of LUAD through Least Absolute Shrinkage and Selection Operator regression analysis. This prognostic signature stratified LUAD patients into low-risk and high-risk groups. The receiver operating characteristic curve and K–M analysis indicated good performance of the DEMRGs signature at predicting OS in the TCGA dataset. Univariate and multivariate Cox regression also revealed that the DEMRGs signature was an independent prognosis factor in LUAD. We noticed that the risk score was substantially related to the clinical parameters of LUAD patients, covering age and stage. Immune analysis results showed that risk score was associated with some immune cells and immune checkpoints. Nomogram also verified the clinical value of the DEMRGs signature. Conclusion: In this study, we constructed a DEMRGs signature and established a prognostic nomogram that is robust and reliable to predict OS in LUAD. Overall, the findings could help with therapeutic customization and personalized therapies.

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“…Accordingly, we have developed a panel of TN-specific mAbs that effectively prevented both harmful HMGB1/TN interaction and resultant macrophage pyroptosis and lethal sepsis [ 172 ]. It suggested that TN domain-specific mAbs may confer protection against lethal sepsis partly by preventing harmful TN/HMGB1 interaction that may adversely trigger macrophage pyroptosis and immunosuppression ( Figure 5 ) [ 173 , 174 ]. This antibody strategy has also suggested a possibility to develop therapeutic antibodies against harmless proteins colluding with sepsis mediators [ 173 , 174 , 175 ].…”

Section: Pharmacological Modulation Of Lps-induced Hmgb1 Release or Actionmentioning

confidence: 99%

“…It suggested that TN domain-specific mAbs may confer protection against lethal sepsis partly by preventing harmful TN/HMGB1 interaction that may adversely trigger macrophage pyroptosis and immunosuppression ( Figure 5 ) [ 173 , 174 ]. This antibody strategy has also suggested a possibility to develop therapeutic antibodies against harmless proteins colluding with sepsis mediators [ 173 , 174 , 175 ].…”

Section: Pharmacological Modulation Of Lps-induced Hmgb1 Release or Actionmentioning

confidence: 99%

“…Despite a robust increase in the understanding of the pathophysiology of sepsis, many antibody-based strategies targeting early cytokines (such as TNF or IL-1) failed in clinical settings. Currently, there is still no effective therapy [ 173 ] other than adjunctive use of antibiotics, fluid resuscitation, and supportive care [ 185 ]. Thus, it would be beneficial to test the therapeutic efficacy of some promising HMGB1 inhibitors in clinical settings.…”

Section: Future Perspectivesmentioning

confidence: 99%

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Endogenous Regulation and Pharmacological Modulation of Sepsis-Induced HMGB1 Release and Action: An Updated Review

Zhu

Wang

Qiang

et al. 2021

Cells

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Sepsis remains a common cause of death in intensive care units, accounting for approximately 20% of total deaths worldwide. Its pathogenesis is partly attributable to dysregulated inflammatory responses to bacterial endotoxins (such as lipopolysaccharide, LPS), which stimulate innate immune cells to sequentially release early cytokines (such as tumor necrosis factor (TNF) and interferons (IFNs))and late mediators (such as high-mobility group box 1, HMGB1). Despite difficulties in translating mechanistic insights into effective therapies, an improved understanding of the complex mechanisms underlying the pathogenesis of sepsis is still urgently needed. Here, we review recent progress in elucidating the intricate mechanisms underlying the regulation of HMGB1 release and action, and propose a few potential therapeutic candidates for future clinical investigations.

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Breaking the bond between tetranectin and HMGB1 in sepsis

Abstract: The interaction between tetranectin and high-mobility group box-1 protein may be manipulated via monoclonal antibodies to improve survival in sepsis (Chen et al. same issue).

Cited by 14 publications

References 10 publications

Characterization of a proteomic profile associated with organ dysfunction and mortality of sepsis and septic shock

Characterization of a proteomic profile associated with organ dysfunction and mortality of sepsis and septic shock

Identification of metabolism-related gene signature in lung adenocarcinoma

Endogenous Regulation and Pharmacological Modulation of Sepsis-Induced HMGB1 Release and Action: An Updated Review

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