Lysophosphatidylcholines modulate immunoregulatory checkpoints in peripheral monocytes and are associated with mortality in people with acute liver failure

Trovato, Francesca M.; Zia, Rabiya; Artru, Florent; Mujib, Salma; Jerome, Ellen; Cavazza, Anna; Coen, Muireann; Wilson, Ian D.; Holmes, Elaine; Morgan, Phillip E.; Singanayagam, Arjuna; Bernsmeier, Christine; Napoli, Salvatore; Bernal, William; Wendon, Julia; Miquel, Rosa; Menon, Krishna; Patel, Vishal C.; Smith, John; Atkinson, Stephen R.; Triantafyllou, Evangelos; McPhail, Mark

doi:10.1016/j.jhep.2022.10.031

Cited by 26 publications

(14 citation statements)

References 56 publications

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“…Second, current lack of universally accepted HBV-based ACLF animal model that represent the disease manifestations, despite the successfulness of our ACLF rat model to resemble the clinical spectrum of the disease. Regardless the shared clinical symptoms between ALF and ACLF [ 69 ], which was previously confirmed even at the monocyte transcriptome level [ 70 ], we cannot exclude the possibility of distinct differences in the disease entity between ACLF and ALF in our animal models, as mice were insensitive to porcine serum in establishing an immune-based ACLF [ 71 ]. If such model is established, the genuine protective capacity of THBS1 knockout could be examined.…”

Section: Discussionmentioning

confidence: 79%

Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure

Hassan,

Liang,

Xin

et al. 2024

BMC Med

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Background The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis. Methods Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice. Results THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (< 28 µg/ml). External validation in ACLF rat serum and livers confirmed the functional association between THBS1, the immune response and hepatocellular apoptosis. Hepatocyte-specific THBS1 knockout improved mouse survival, significantly repressed major inflammatory cytokines, enhanced the expression of several anti-inflammatory mediators and impeded hepatocellular apoptosis. Conclusions THBS1 might be an ACLF disease development-related biomarker, promoting inflammatory responses and hepatocellular apoptosis, that could provide clinicians with a new molecular target for improving diagnostic and therapeutic strategies. Graphical Abstract

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Section: Discussionmentioning

confidence: 79%

Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure

Hassan,

Liang,

Xin

et al. 2024

BMC Med

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“…Metabolites associated with the arachidonic acid pathway, such as PGE 2, have been identified as inflammation‐related biomarkers of metabolic disorders in systemic inflammatory processes such as ureteral stent disease (Huang et al., 2020). LPC16:0 and 1‐oleoylglycerophosphocholine have been associated with glycerophospholipid metabolism, and LPCs and their derivatives have been reported to be positively correlated with inflammation (Trovato et al., 2023; Wang et al., 2022). 12,13‐DiHOME belongs to the group of hydroxyoctadecadienoic acids (HODEs) and may be associated with inflammation because HODEs can be produced from linoleic acid via lipoxygenase activated by inflammatory reactions (Kikut et al., 2020).…”

Section: Resultsmentioning

confidence: 99%

Identification of lymph node adulteration in minced pork by comprehensive metabolomics and lipidomics approach based on UPLC/LTQ‐Orbitrap MS

Wang,

Jiang,

et al. 2024

Journal of Food Science

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The deliberate pork adulteration with lymph nodes is a common adulteration phenomenon, and it poses a serious threat to public health and food safety. An untargeted metabolomics and lipidomics approach based on ultrahigh performance liquid chromatography coupled with linear ion trap quadrupole‐Orbitrap high resolution mass spectrometry (MS) was used to distinguish lymph nodes from minced pork. The principal component analysis and orthogonal projection to latent structures discriminant analysis models were established with the good of fitness and predictivity. The results showed that there were significant differences in metabolites and lipids between lymph nodes and pork. A total of 16 significantly differentiated metabolites were identified, of which 1‐palmitoylglycerophosphocholine, 12,13‐dihydroxy‐9‐octadecenoic acid, and prostaglandin E2 (PGE2) were positively correlated with lymph node content and were identified as potential markers of lymph nodes. These three markers were combined to create a binary logistic regression model, and a combined‐factor exceeding 0.75 was ultimately identified as a marker for pork adulteration with lymph nodes. The desorption electrospray ionization‐MS images showed that PGE2 had a higher relative abundance in the lymph node region than in adjacent non‐lymph node regions, indicating that PGE2 was a marker that contributed significantly for identifying lymph nodes adulteration into pork. Our results provide a theoretical basis for identifying lymph node adulteration, which will contribute to combating fraud in the meat industry.

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“…Furthermore, a single-center retrospective study revealed that a high monocyte-to-lymphocyte ratio was a risk factor for clinical progression in patients with pulmonary Mycobacterium avium complex disease 41 . Additionally, a growing body of research indicates that monocytes and macrophages play crucial roles in the prognosis of non-infectious diseases 34 , 42 . Interestingly, the results of the present study align with the findings of the aforementioned studies, revealing a markedly elevated level of monocytes in the SCI group.…”

Section: Discussionmentioning

confidence: 99%

Prediction model for spinal cord injury in spinal tuberculosis patients using multiple machine learning algorithms: a multicentric study

Feng,

Wang,

Liu

et al. 2024

Sci Rep

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Spinal cord injury (SCI) is a prevalent and serious complication among patients with spinal tuberculosis (STB) that can lead to motor and sensory impairment and potentially paraplegia. This research aims to identify factors associated with SCI in STB patients and to develop a clinically significant predictive model. Clinical data from STB patients at a single hospital were collected and divided into training and validation sets. Univariate analysis was employed to screen clinical indicators in the training set. Multiple machine learning (ML) algorithms were utilized to establish predictive models. Model performance was evaluated and compared using receiver operating characteristic (ROC) curves, area under the curve (AUC), calibration curve analysis, decision curve analysis (DCA), and precision-recall (PR) curves. The optimal model was determined, and a prospective cohort from two other hospitals served as a testing set to assess its accuracy. Model interpretation and variable importance ranking were conducted using the DALEX R package. The model was deployed on the web by using the Shiny app. Ten clinical characteristics were utilized for the model. The random forest (RF) model emerged as the optimal choice based on the AUC, PRs, calibration curve analysis, and DCA, achieving a test set AUC of 0.816. Additionally, MONO was identified as the primary predictor of SCI in STB patients through variable importance ranking. The RF predictive model provides an efficient and swift approach for predicting SCI in STB patients.

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Lysophosphatidylcholines modulate immunoregulatory checkpoints in peripheral monocytes and are associated with mortality in people with acute liver failure

Cited by 26 publications

References 56 publications

Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure

Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure

Identification of lymph node adulteration in minced pork by comprehensive metabolomics and lipidomics approach based on UPLC/LTQ‐Orbitrap MS

Prediction model for spinal cord injury in spinal tuberculosis patients using multiple machine learning algorithms: a multicentric study

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