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Combination of HBA1, TTR, and SERPINF2 in plasma defines phenotype correlated with severe burn outcome.

ABSTRACT: Recent advancements in proteomics allow for the concurrent identification and quantification of multiple proteins. This study aimed to identify proteins associated with severe burn pathology and establish a clinically useful molecular pathology classification. In a retrospective observational study, blood samples were collected from severe burn patients. Proteins were measured using mass spectrometry, and prognosis-related proteins were extracted by comparing survivors and non-survivors. Enrichment and ROC analyses evaluated the extracted proteins, followed by latent class analysis. Measurements were performed on 83 burn patients. In the non-survivor group, ten proteins significantly changing on the day of injury were associated with metabolic processes and toxin responses. ROC analysis identified HBA1, TTR, and SERPINF2 with AUCs > 0.8 as predictors of 28-day mortality. Latent class analysis classified three molecular pathotypes, and plasma mass spectrometry revealed ten proteins associated with severe burn prognosis. Molecular pathotypes based on HBA1, TTR, and SERPINF2 significantly correlated with outcomes.

SUBMITTER: Onishi S

PROVIDER: S-EPMC10368932 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Combination of HBA1, TTR, and SERPINF2 in plasma defines phenotype correlated with severe burn outcome.

Onishi Shinya S Matsumoto Hisatake H Sugihara Fuminori F Ebihara Takeshi T Matsuura Hiroshi H Osuka Akinori A Okuzaki Daisuke D Ogura Hiroshi H Oda Jun J

iScience 20230703 8

Recent advancements in proteomics allow for the concurrent identification and quantification of multiple proteins. This study aimed to identify proteins associated with severe burn pathology and establish a clinically useful molecular pathology classification. In a retrospective observational study, blood samples were collected from severe burn patients. Proteins were measured using mass spectrometry, and prognosis-related proteins were extracted by comparing survivors and non-survivors. Enrichm ...[more]

PMID: 37502255

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Project description:ObjectiveWe investigated the relationship between plasma miRNAs levels and inflammatory characteristics in asthmatic patients.MethodsEligible adults with untreated asthma (n = 35) underwent a clinical assessment, sputum induction, and assessment of pulmonary function test and Asthma Control Test (ACT) scores. Asthma phenotypes were defined using the sputum cell count. miR-199a-5p expression was measured using quantitative real-time polymerase chain reaction (qPCR). Lipopolysaccharide (LPS) stimulation was used to detect miR-199a-5p secretion from peripheral blood-derived neutrophil, lymphocyte, macrophage and BEAS-2B cells. The correlation of miR-199a-5p expression with clinical parameters was analyzed using multiple linear regression analysis. In silico analysis predicted the target genes and signaling pathway of miR-199a-5p. Transfection of miR-199a-5p mimics in human airway smooth muscle cells (HASMCs) was performed in vitro.ResultsThe miRNA-199a-5p levels in plasma and sputum increased significantly in patients with neutrophilic asthma compared to healthy subjects (ps = 0.014 and 0.006, respectively). Expression of miR-199a-5p in the plasma of asthmatic patients positively correlated with sputum miR-199a-5p expression (r = 0.511, p = 0.021). The miR-199a-5p level was only elevated with LPS stimulation in neutrophils but not macrophages, lymphocytes, or epithelial cells from healthy controls (p < 0.01). miR-199a-5p expression increased in response to LPS (p = 0.005) and LPS combined with IL-4 (p = 0.003), but not IL-4 alone. However, peripheral neutrophils from eosinophilic asthma patients did not respond to LPS with increased miR-199a-5p expression (n = 5, p > 0.05) in contrast to the significant response from neutrophilic patients (n = 4, p < 0.0001). miR-199a-5p negatively correlated with FEV1, FVC and PEF (r = -0.377, p = 0.026; r = -0.419, p = 0.012; and r = -0.392, p = 0.024, respectively). Multivariate correlation analysis confirmed that the plasma miR-199a-5p levels negatively correlated with FEV1 in patients with asthma (Adjusted R2 = 0.164, p = 0.015). In silico analysis suggested that the WNT signaling pathway participates in miR-199a-5p mediation of smooth muscle cell hypertrophy. In vitro experiment, miR-199a-5p mimics inhibited the protein expressions of WNT2 and WNT4, decreased the c-myc expression and dramatically increased the Sm-MHC expression in HASMCs.ConclusionPlasma miR-199a-5p was increased in neutrophilic asthma and negatively correlated with pulmonary function, which suggests that miR-199a-5p actively contributes to disease pathogenesis by modulating the inflammatory process and transferring the signal from inflammatory cells to structure cells.

Project description:BackgroundCombination therapy with tazobactam/ceftolozane (TAZ/CTLZ) and high-dose aminoglycosides has been reported to be efficacious in extensively drug-resistant (XDR)-Pseudomonas aeruginosa infection. However, there are no reports of efficacy in XDR-P. aeruginosa infection for combination therapy with low-dose aminoglycosides and TAZ/CTLZ. Herein, we describe a rare case of severe burn injury patients with persistent bacteremia due to XDR-P. aeruginosa, which was successfully treated with TAZ/CTLZ and low-dose tobramycin (TOB).Case presentationA 31-year-old man was admitted to the intensive care unit with severe burn injury involving 52% of the total body surface area and a prognostic burn index of 79.5. The patient had recurrent bacterial infections since admission, and blood cultures collected on the 37th day of admission revealed the presence of P. aeruginosa strains that were resistant to all β-lactams and amikacin (AMK). The results of the antimicrobial synergistic study showed no synergistic effect of low-dose meropenem (MEPM) and AMK combination therapy. The patient had acute renal failure, and it was difficult to increase the dose of MEPM and AMK, respectively. Thus, we initiated TAZ/CTLZ 1.5 g/8 h instead of the AMK and MEPM combination therapy on the 43rd day of hospitalization. Low-dose TAZ/CTLZ was continued because of prolonged renal dysfunction and resulted in a transient clinical improvement. However, the dosage of TAZ/CTLZ could be increased as the renal function improved, but despite an increased TAZ/CTLZ dose, bacteremia persisted, and the blood cultures remained positive. Thus, TOB was added to TAZ/CTLZ at low doses for synergistic effect against Gram-negative bacteria. Blood cultures collected after initiation of combination therapy with TAZ/CTLZ and low-dose TOB were negative on two consecutive follow-up evaluations. Thereafter, although the patient had several episodes of fever and increased inflammatory response, blood cultures consistently tested negative, and all of the wounds healed. On the 93rd day, due to the good healing progress, the patient was transferred to another hospital.ConclusionsTAZ/CTLZ and low-dose TOB combination therapy showed the potential for synergistic effects. Our present report suggests a novel synergistic treatment strategy for rare cases that are refractory to the treatment of infections, such as XDR-P. aeruginosa infection.

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Combination of HBA1, TTR, and SERPINF2 in plasma defines phenotype correlated with severe burn outcome.

Publications

Combination of HBA1, TTR, and SERPINF2 in plasma defines phenotype correlated with severe burn outcome.

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