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1.
Food Chem ; 371: 131384, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34808777

RESUMO

In-package cold plasma (ICP) pretreatment is an emerging non-thermal food processing methods. In the current study, ICP on the formation of polycyclic aromatic hydrocarbons (PAHs) in grilled beef steaks with different oils and fats was evaluated, the influence of prolonged storage periods (1 d, 2 d) of raw meat after ICP pretreatment on the PAH inhibitory effect was investigated. The results showed that sunflower seed oil had an inhibitory effect on PAH formation; the groups with ICP pretreatment showed a significant decrease in PAH content (p < 0.05) according to the UHPLC results, inhibitory rates were dependent on the original contents in each group without ICP pretreatment, ranging from 35% to 96%. The optimal condition was grilling immediately after ICP pretreatment, and the results indicated that the nonpolar radical scavenging activity (RSA) of ungrilled meat was negatively correlated with PAH8 contents according the DPPH assay, while ICP pretreatment enhanced the RSAoil of raw meat.


Assuntos
Gases em Plasma , Hidrocarbonetos Policíclicos Aromáticos , Animais , Bovinos , Carvão Vegetal , Culinária , Óleos , Hidrocarbonetos Policíclicos Aromáticos/análise
3.
Artigo em Inglês | MEDLINE | ID: mdl-34817638

RESUMO

BACKGROUND: Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy. METHOD: Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32). RESULTS: Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032). CONCLUSION: This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.

4.
Front Immunol ; 12: 766178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721438

RESUMO

Neuroinflammation is a key process in the pathogenesis of subarachnoid hemorrhage (SAH) and contributes to poor outcome in patients. The purpose of this study is to explore the effect of triggering receptor expressed on myeloid cells 1 (TREM1) in the SAH, as well as its potential mechanism. In our study, plasma levels of soluble TREM1 was increased significantly after SAH and correlated to SAH severity and serum C-reactiveprotein. TREM1 inhibitory peptide LP17 alleviated the neurological deficits, attenuated brain water content, and reduced neuronal damage after SAH. Meanwhile, TREM1 inhibitory peptide decreased neuroinflammation (evidenced by the decreased levels of markers including IL-6, IL-1ß, TNF-α) by attenuating proinflammatory subtype transition of microglia (evidenced by the decreased levels of markers including CD68, CD16, CD86) and decreasing the formation of neutrophil extracellular traps (evidenced by the decreased levels of markers including CitH3, MPO, and NE). Further mechanistic study identified that TREM1 can activate downstream proinflammatory pathways through interacting with spleen tyrosine kinase (SYK). In conclusion, inhibition of TREM1 alleviates neuroinflammation by attenuating proinflammatory subtype transition of microglia and decreasing the formation of neutrophil extracellular traps through interacting with SYK after SAH. TREM1 may be a a promising therapeutic target for SAH.

6.
J Proteome Res ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34672606

RESUMO

The study of proteins circulating in blood offers tremendous opportunities to diagnose, stratify, or possibly prevent diseases. With recent technological advances and the urgent need to understand the effects of COVID-19, the proteomic analysis of blood-derived serum and plasma has become even more important for studying human biology and pathophysiology. Here we provide views and perspectives about technological developments and possible clinical applications that use mass-spectrometry(MS)- or affinity-based methods. We discuss examples where plasma proteomics contributed valuable insights into SARS-CoV-2 infections, aging, and hemostasis and the opportunities offered by combining proteomics with genetic data. As a contribution to the Human Proteome Organization (HUPO) Human Plasma Proteome Project (HPPP), we present the Human Plasma PeptideAtlas build 2021-07 that comprises 4395 canonical and 1482 additional nonredundant human proteins detected in 240 MS-based experiments. In addition, we report the new Human Extracellular Vesicle PeptideAtlas 2021-06, which comprises five studies and 2757 canonical proteins detected in extracellular vesicles circulating in blood, of which 74% (2047) are in common with the plasma PeptideAtlas. Our overview summarizes the recent advances, impactful applications, and ongoing challenges for translating plasma proteomics into utility for precision medicine.

7.
J Exp Clin Cancer Res ; 40(1): 300, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556175

RESUMO

BACKGROUND: The global epidemiological studies reported lower cancer risk after long-term use of contraceptives. Our systematic studies demonstrated that abortifacients are effective in preventing cancer metastases induced by circulating tumor cells (CTCs). However, the molecular and cellular mechanisms by which abortifacients prevent CTC-based cancer metastases are almost unknown. The present studies were designed to interdisciplinarily explore similarities and differences between embryo implantation and cancer cell adhesion/invasion. METHODS: Biomarker expressions on the seeding embryo JEG-3 and cancer MCF-7 cells, as well as embedding uterine endometrial RL95-2 and vascular endothelial HUVECs cells were examined and compared before and after treatments with 17ß-estradiol plus progesterone and abortifacients. Effects of oral metapristone and mifepristone on embryo implantation in normal female mice and adhesion/invasion of circulating tumor cells (CTCs) in BALB/C female mice were examined. RESULTS: Both embryo JEG-3 and cancer MCF-7 cells expressed high sLex, CD47, CAMs, while both endometrial RL95-2 and endothelial HUVECs exhibited high integrins and ICAM-1. Near physiological concentrations of 17ß-estradiol plus progesterone promoted migration and invasion of JEG-3 and MCF-7 cells via upregulating integrins and MMPs. Whereas, mifepristone and metapristone significantly inhibited migration and invasion of JEG-3 and MCF-7 cells, and inhibited JEG-3 and MCF-7 adhesion to matrigel, RL95-2 cells and HUVECs, respectively. The inhibitions were realized by downregulating sLex, MMPs in JEG-3 and MCF-7 cells, and downregulating integrins in RL95-2 cells and HUVECs, respectively. Mifepristone and metapristone significantly inhibited both embryo implantation and cancer cell metastasis in mice. CONCLUSIONS: The similarities between the two systems provide fundamentals for abortifacients to intervene CTC adhesion/invasion to the distant metastatic organs. The present studies offer the rationale to repurpose abortifacients for safe and effective cancer metastasis chemoprevention.

8.
J Agric Food Chem ; 69(38): 11470-11484, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34543010

RESUMO

The development of new green fungicides based on the structural optimization of natural products can effectively solve the problems of low safety and high pathogen resistance of traditional fungicides. In this paper, based on pyrazole amide compound h-I-9 with excellent fungicidal activity discovered in the previous work, a series of l-serine-derived pyrazole amide and waltherione alkaloid-derived pyrazole ester derivatives were synthesized. The structures were successively identified by 1H NMR, 13C NMR, high-resolution mass spectrometry, and X-ray single-crystal diffraction. The in vitro and in vivo fungicidal activity screening demonstrated that compound II-5 showed a good inhibition rate against Physalospora piricola. A transmission electron microscope and fluorescence microscope observation further revealed that compound II-5 may cause damage to the cell membranes and vacuoles, and the hyphae treated with II-5 could produce obvious and easily observed blue fluorescence. The succinate dehydrogenase (SDH) enzymatic activity and molecular docking simulation indicated that compounds I-3 and I-4 may be potential SDH inhibitors against Alternaria sp.


Assuntos
Alcaloides , Produtos Biológicos , Fungicidas Industriais , Alcaloides/farmacologia , Amidas/farmacologia , Produtos Biológicos/farmacologia , Ésteres , Fungicidas Industriais/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirazóis/farmacologia , Serina , Relação Estrutura-Atividade , Succinato Desidrogenase/metabolismo
9.
Front Neurol ; 12: 688019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589044

RESUMO

Objective: To evaluate the efficacy and safety of tirofiban for patients with acute ischemic stroke (AIS), especially posterior circulation stroke (PCS). Methods: We enrolled consecutive patients with AIS who suffered large artery occlusion (LAO) and underwent mechanical thrombectomy (MT) between January 2016 and May 2020. Patients were divided into two groups according to whether tirofiban was used during MT. The primary efficacy outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-2 at 3 months. The safety outcomes were the rate of mortality at 3 months and the presence of intracranial hemorrhage (ICH) and symptomatic intracranial hemorrhage (sICH). Cohorts were balanced using 1:1 propensity score matching (PSM). Subgroup analysis was further performed to compare the efficacy and safety of tirofiban between the anterior circulation stroke (ACS) and PCS groups. Results: A total of 292 patients were eligible for this study and divided into the tirofiban group (n = 51) and the no-tirofiban group (n = 241). In the propensity-score-matched cohort, the tirofiban group had a higher rate of favorable outcomes than the no-tirofiban group (49.0 vs. 25.5%, p = 0.014), and the mortality at 3 months showed a greater downward trend in the tirofiban group than the no-tirofiban group (15.6 vs. 33.3% p = 0.064). The risk of sICH and ICH was the same between the tirofiban and control groups (17.6 vs. 27.4% p = 0.236, 31.3 vs. 45.1% p = 0.154, respectively). Tirofiban use was predictive of favorable outcomes [adjusted odds ratio (aOR) = 2.87, 95% confidence interval (CI) 1.52-6.44, p = 0.043] after multiple logistic regression analysis. Subgroup analysis revealed that tirofiban use was significantly associated with favorable outcomes in ACS (aOR = 3.66, 95% CI 1.24-5.22, p = 0.019) but not in PCS (aOR = 1.12, 95% CI 0.47-7.52, p = 0.570). Conclusion: We demonstrated that tirofiban may be associated with improving favorable outcome for the AIS patients who underwent MT, without increasing ICH or sICH. Furthermore, our results indicated that for PCS patients tirofiban may not be associated with favorable outcome, and more comprehensive randomized controlled trials are needed to confirm this finding.

10.
Signal Transduct Target Ther ; 6(1): 304, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404759

RESUMO

A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host's innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , Imunidade Humoral , SARS-CoV-2/imunologia , Proteínas não Estruturais Virais/imunologia , COVID-19/mortalidade , Estado Terminal , Intervalo Livre de Doença , Epitopos/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Análise Serial de Proteínas , Taxa de Sobrevida
11.
BMC Plant Biol ; 21(1): 388, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416870

RESUMO

BACKGROUND: Soybean is a globally important legume crop that provides a primary source of high-quality vegetable protein and oil. Seed protein content (SPC) is a valuable quality trait controlled by multiple genes in soybean. RESULTS: In this study, we performed quantitative trait loci (QTL) mapping, QTL-seq, and RNA sequencing (RNA-seq) to reveal the genes controlling protein content in the soybean by using the high protein content variety Nanxiadou 25. A total of 50 QTL for SPC distributed on 14 chromosomes except chromosomes 4, 12, 14, 17, 18, and 19 were identified by QTL mapping using 178 recombinant inbred lines (RILs). Among these QTL, the major QTL qSPC_20-1 and qSPC_20-2 on chromosome 20 were repeatedly detected across six tested environments, corresponding to the location of the major QTL detected using whole-genome sequencing-based QTL-seq. 329 candidate DEGs were obtained within the QTL region of qSPC_20-1 and qSPC_20-2 via gene expression profile analysis. Nine of which were associated with SPC, potentially representing candidate genes. Clone sequencing results showed that different single nucleotide polymorphisms (SNPs) and indels between high and low protein genotypes in Glyma.20G088000 and Glyma.16G066600 may be the cause of changes in this trait. CONCLUSIONS: These results provide the basis for research on candidate genes and marker-assisted selection (MAS) in soybean breeding for seed protein content.


Assuntos
Mapeamento Cromossômico , Estudos de Associação Genética , Proteínas de Plantas/análise , Proteínas de Plantas/genética , Sementes/química , Soja/química , Soja/genética , Produtos Agrícolas/química , Produtos Agrícolas/genética , Regulação da Expressão Gênica de Plantas , Marcadores Genéticos , Variação Genética , Genótipo , Locos de Características Quantitativas , Análise de Sequência de RNA
12.
Angew Chem Int Ed Engl ; 60(39): 21521-21528, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34346153

RESUMO

A diazirine-based four-armed cross-linker (4CNN) with a tetrahedron geometry is presented for efficient patterning of polymeric semiconductors by photo-induced carbene insertion. After blending of 4CNN with no more than 3 % (w/w), photo-patterning of p-, n-, and ambipolar semiconducting polymers with side alkyl chains was achieved; regular patterns with size as small as 5 µm were prepared with appropriate photomasks after 365 nm irradiation for just 40 s. The interchain packing order and the thin film morphology were nearly unaltered after the cross-linking and the semiconducting properties of the patterned thin films were mostly retained. A complementary-like inverter with a gain value of 112 was constructed easily by two steps of photo-patterning of the p-type and n-type semiconducting polymers. The results show that 4CNN is a new generation of cross-linker for the photo-patterning of polymeric semiconductors for all-solution-processible flexible electronic devices.

13.
J Neuroinflammation ; 18(1): 154, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233703

RESUMO

BACKGROUND: Complex changes in the brain microenvironment following traumatic brain injury (TBI) can cause neurological impairments for which there are few efficacious therapeutic interventions. The reactivity of astrocytes is one of the keys to microenvironmental changes, such as neuroinflammation, but its role and the molecular mechanisms that underpin it remain unclear. METHODS: Male C57BL/6J mice were subjected to the controlled cortical impact (CCI) to develop a TBI model. The specific ligand of AXL receptor tyrosine kinase (AXL), recombinant mouse growth arrest-specific 6 (rmGas6) was intracerebroventricularly administered, and selective AXL antagonist R428 was intraperitoneally applied at 30 min post-modeling separately. Post-TBI assessments included neurobehavioral assessments, transmission electron microscopy, immunohistochemistry, and western blotting. Real-time polymerase chain reaction (RT-PCR), siRNA transfection, and flow cytometry were performed for mechanism assessments in primary cultured astrocytes. RESULTS: AXL is upregulated mainly in astrocytes after TBI and promotes astrocytes switching to a phenotype that exhibits the capability of ingesting degenerated neurons or debris. As a result, this astrocytic transformation promotes the limitation of neuroinflammation and recovery of neurological dysfunction. Pharmacological inhibition of AXL in astrocytes significantly decreased astrocytic phagocytosis both in vivo and in primary astrocyte cultures, in contrast to the effect of treatment with the rmGas6. AXL activates the signal transducer and activator of the transcription 1 (STAT1) pathway thereby further upregulating ATP-binding cassette transporter 1 (ABCA1). Moreover, the supernatant from GAS6-depleted BV2 cells induced limited enhancement of astrocytic phagocytosis in vitro. CONCLUSION: Our work establishes the role of AXL in the transformation of astrocytes to a phagocytic phenotype via the AXL/STAT1/ABCA1 pathway which contributes to the separation of healthy brain tissue from injury-induced cell debris, further ameliorating neuroinflammation and neurological impairments after TBI. Collectively, our findings provide a potential therapeutic target for TBI.

14.
Database (Oxford) ; 20212021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244719

RESUMO

Trained immunity is a newly emerging concept that defines the ability of the innate immune system to form immune memory and provide long-lasting protection against previously encountered antigens. Accumulating evidence reveals that trained immunity not only has broad benefits to host defense but is also harmful to the host in chronic inflammatory diseases. However, all trained immunity-related information is scattered in the literature and thus is difficult to access. Here, we describe Trained Immunity DataBase (TIDB), a comprehensive database that provides well-studied trained immunity-related genes from human, rat and mouse as well as the related literature evidence. Moreover, TIDB also provides three modules to analyze the function of the trained-immunity-related genes of interest, including Reactome pathway over-representation analysis, Gene Ontology enrichment analysis and protein-protein interaction subnetwork reconstruction. We believe TIDB will help developing valuable strategies for vaccine design and immune-mediated disease therapy. Database URL: http://www.ieom-tm.com/tidb.


Assuntos
Imunidade Inata , Animais , Imunidade Inata/genética , Camundongos , Ratos
15.
Methods Mol Biol ; 2344: 99-106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34115354

RESUMO

Autoantibodies are humoral antibodies against self-proteins and play vital roles in maintaining the homeostasis. Autoantibodies can also target posttranslational modifications (PTMs) of proteins and the identification of new PTM autoantibodies is important to identify biomarkers for the early diagnosis of cancer and autoimmune diseases. In this chapter, we describe a method to detect PTM autoantibodies using citrullinated peptide microarray as an example. This method can be used to screen serum autoantibodies for different human diseases.


Assuntos
Autoanticorpos/análise , Doenças Autoimunes/diagnóstico , Análise Serial de Proteínas , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Biomarcadores/análise , Humanos , Processamento de Proteína Pós-Traducional
16.
Dev Comp Immunol ; 124: 104175, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34147569

RESUMO

Bacterial disease outbreaks in filter feeder bivalve Hyriopsis cumingii as water contamination become more frequent in the water ecosystem, especially in intensive aquaculture habitats. To characterize host-pathogen interactions between H. cumingii and bacterial infection, we investigated the effects of Stenotrophomonas maltophilia HOP3 and Aeromonas veronii GL1 on the antioxidant response, tissue invasion and transcriptome expression of H. cumingii by infectivity trials. We showed that bacterial infections resulted in tubular necrosis of the hepatopancreas and induced the acute immune response in H. cumingii. The transcriptomic study identified a total of 5957 differentially expressed genes (DEGs) after A. veronii challenge. These DEGs were implicated in 302 KEGG pathways, notably in Apoptosis, Phagosome and Lysosome. The results showed that the relative expressions of all six immune-related DEGs were effectively stimulated with A. veronii, accompanied by tissue differences. Overall, these findings will contribute to an analysis of the immune response of H. cumingii to bacterial infection at the transcriptomic level and its genomic resource for research.

17.
Front Microbiol ; 12: 647304, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025607

RESUMO

Intracerebral hemorrhage (ICH) induces a strong hematoma-related neuroinflammatory reaction and alters peripheral immune homeostasis. Recent research has found that gut microbiota plays a role in neurodegeneration and autoimmune diseases by regulating immune homeostasis and neuroinflammation. Therefore, we investigated the relationship between ICH, microbiota alteration, and immune responses after hematoma-induced acute brain injury. In our study, we used a mouse model of ICH, and 16S ribosomal RNA sequencing showed that ICH causes gut microbiota dysbiosis, which in turn affects ICH outcome through immune-mediated mechanisms. There was prominent reduced species diversity and microbiota overgrowth in the dysbiosis induced by ICH, which may reduce intestinal motility and increase gut permeability. In addition, recolonizing ICH mice with a normal health microbiota ameliorates functional deficits and neuroinflammation after ICH. Meanwhile, cell-tracking studies have demonstrated the migration of intestinal lymphocytes to the brain after ICH. In addition, therapeutic transplantation of fecal microbiota improves intestinal barrier damage. These results support the conclusion that the gut microbiome is a target of ICH-induced systemic alteration and is considered to have a substantial impact on ICH outcome.

19.
Nature ; 592(7854): 433-437, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33790463

RESUMO

Upon gamete fusion, animal egg cells secrete proteases from cortical granules to establish a fertilization envelope as a block to polyspermy1-4. Fertilization in flowering plants is more complex and involves the delivery of two non-motile sperm cells by pollen tubes5,6. Simultaneous penetration of ovules by multiple pollen tubes (polytubey) is usually avoided, thus indirectly preventing polyspermy7,8. How plant egg cells regulate the rejection of extra tubes after successful fertilization is not known. Here we report that the aspartic endopeptidases ECS1 and ECS2 are secreted to the extracellular space from a cortical network located at the apical domain of the Arabidopsis egg cell. This reaction is triggered only after successful fertilization. ECS1 and ECS2 are exclusively expressed in the egg cell and transcripts are degraded immediately after gamete fusion. ECS1 and ESC2 specifically cleave the pollen tube attractor LURE1. As a consequence, polytubey is frequent in ecs1 ecs2 double mutants. Ectopic secretion of these endopeptidases from synergid cells led to a decrease in the levels of LURE1 and reduced the rate of pollen tube attraction. Together, these findings demonstrate that plant egg cells sense successful fertilization and elucidate a mechanism as to how a relatively fast post-fertilization block to polytubey is established by fertilization-induced degradation of attraction factors.


Assuntos
Arabidopsis/metabolismo , Endopeptidases/metabolismo , Fertilização , Óvulo Vegetal/metabolismo , Tubo Polínico/metabolismo , Pólen/metabolismo , Arabidopsis/citologia , Arabidopsis/enzimologia , Proteínas de Arabidopsis/metabolismo , Fusão Celular , Óvulo Vegetal/enzimologia , Pólen/enzimologia
20.
J Thromb Haemost ; 19(7): 1738-1751, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825327

RESUMO

BACKGROUND: Pulmonary embolism (PE) is a leading cause of cardiovascular mortality worldwide. Rapid and accurate diagnosis and risk stratification are crucial for timely treatment options, especially in high-risk PE. OBJECTIVES: The study aims to profile the comprehensive changes of plasma proteomes in PE patients and identify the potential biomarkers for both diagnosis and risk stratification. PATIENTS/METHODS: Based on the data-independent acquisition mass spectrometry and antibody array proteomic technology, we screened the plasma samples (13 and 32 proteomes, respectively) in two independent studies consisting of high-risk PE patients, non-high-risk PE patients, and healthy controls. Some significantly differentially expressed proteins were quantified by ELISA in a new study group with 50 PE patients and 26 healthy controls. RESULTS: We identified 207 and 70 differentially expressed proteins in PE and high-risk PE. These proteins were involved in multiple thrombosis-associated biological processes including blood coagulation, inflammation, injury, repair, and chemokine-mediated cellular response. It was verified that five proteins including SAA1, S100A8, TNC, GSN, and HRG had significant change in PE and/or in high-risk PE. The receiver operating characteristic curve analysis based on binary logistic regression showed that the area under the curve (AUC) of SAA1, S100A8, and TNC in PE diagnosis were 0.882, 0.788, and 0.795, and AUC of S100A8 and TNC in high-risk PE diagnosis were 0.773 and 0.720. CONCLUSION: As predictors of inflammation or injury repair, SAA1, S100A8, and TNC are potential plasma biomarkers for the diagnosis and risk stratification of PE.


Assuntos
Proteômica , Embolia Pulmonar , Biomarcadores , Humanos , Espectrometria de Massas , Embolia Pulmonar/diagnóstico , Medição de Risco
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