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1.
J Infect Dis ; 223(1): 19-22, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33083826

RESUMO

It is critical to identify potential causal targets for SARS-CoV-2, which may guide drug repurposing options. We assessed the associations between genetically predicted protein levels and COVID-19 severity. Leveraging data from the COVID-19 Host Genetics Initiative comparing 6492 hospitalized COVID-19 patients and 1 012 809 controls, we identified 18 proteins with genetically predicted levels to be associated with COVID-19 severity at a false discovery rate of <0.05, including 12 that showed an association even after Bonferroni correction. Of the 18 proteins, 6 showed positive associations and 12 showed inverse associations. In conclusion, we identified 18 candidate proteins for COVID-19 severity.


Assuntos
Proteínas Sanguíneas/análise , /genética , Estudos de Associação Genética , Estudos de Casos e Controles , Humanos , Índice de Gravidade de Doença
3.
Sci Rep ; 10(1): 22418, 2020 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-33376242

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over forty million patients worldwide. Although most coronavirus disease 2019 (COVID-19) patients have a good prognosis, some develop severe illness. Markers that define disease severity or predict clinical outcome need to be urgently developed as the mortality rate in critical cases is approximately 61.5%. In the present study, we performed in-depth proteome profiling of undepleted plasma from eight COVID-19 patients. Quantitative proteomic analysis using the BoxCar method revealed that 91 out of 1222 quantified proteins were differentially expressed depending on the severity of COVID-19. Importantly, we found 76 proteins, previously not reported, which could be novel prognostic biomarker candidates. Our plasma proteome signatures captured the host response to SARS-CoV-2 infection, thereby highlighting the role of neutrophil activation, complement activation, platelet function, and T cell suppression as well as proinflammatory factors upstream and downstream of interleukin-6, interleukin-1B, and tumor necrosis factor. Consequently, this study supports the development of blood biomarkers and potential therapeutic targets to aid clinical decision-making and subsequently improve prognosis of COVID-19.


Assuntos
Proteínas Sanguíneas/análise , Índice de Gravidade de Doença , Adulto , Idoso , Biomarcadores/sangue , /patologia , Cromatografia Líquida de Alta Pressão , Ativação do Complemento/imunologia , Citocinas/sangue , Perfilação da Expressão Gênica , Humanos , Espectrometria de Massas , Pessoa de Meia-Idade , Ativação de Neutrófilo/imunologia , Ativação Plaquetária/imunologia , Proteoma/metabolismo , Fatores Supressores Imunológicos/sangue , Linfócitos T/imunologia
4.
Medicine (Baltimore) ; 99(45): e22971, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157938

RESUMO

Coronavirus disease 2019 (COVID-19) has rapidly spread on a global scale. Therefore, it is urgent to identify risk factors that could be associated with severe type of COVID-19 from common type.For this retrospective study, we recruited patients with COVID-19 in Wuhan and Zhoukou. Patients were classified into a severe group and common group based on guidelines after admission. Clinical manifestations and laboratory tests were compared, and univariate binary logistic regression and multivariate regression analyses were applied to assess potential risk factors.A total of 126 patients were recruited from January 23 to March 23, 2020. Ninety cases were identified as the common type and 36 as the severe type. The average age in the severe group was significantly older than that in the common group (P = .008). Patients with severe COVID-19 exhibited higher proportions of dyspnea (P = .001), weakness (P = .023), and diarrhea (P = .046). Moreover, there were more patients with hypertension (P = .01) or coinfection (P = .001) in the severe group than in the common group. Additionally, severe COVID-19 was associated with increased neutrophil counts (P < .001), C-reactive protein (P < .001), procalcitonin (P = .024) and decreased lymphocyte counts (P = .001), hemoglobin (P < .001), total protein (TP) (P < .001), and albumin (ALB) (P < .001). Based on logistic regression analysis, dyspnea (P < .001), TP (P = .042), and ALB (P = .003) were independent risk factors for severe disease.Patients with lower TP, ALB, and dyspnea should be carefully monitored, and early intervention should be implemented to prevent the development of severe disease.


Assuntos
Infecções por Coronavirus/diagnóstico , Progressão da Doença , Hospitalização , Pneumonia Viral/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Proteínas Sanguíneas/análise , Proteína C-Reativa/análise , China , Dispneia/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica Humana/análise , Adulto Jovem
5.
Medicine (Baltimore) ; 99(42): e22802, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080754

RESUMO

The agents used in the treatment of acute lymphoblastic leukaemia (ALL) might affect the oral health of cancer patients.The study aims to assess the changes in the levels of immunoglobulin A (IgA) in saliva and blood, during first 22 days of intensive chemotherapy of ALL in children.Saliva and blood samples were taken from 24 patients, including 13 boys and 11 girls (age range: 4 - 17 years) on days 1, 8 and 22 of treatment. The levels of immunoglobulin A and total protein were estimated in samples at each time-point. The distribution of the quantitative variables was assessed using the Shapiro-Wilk test. Non-parametric statistics were used to compare the levels of repeated measurements and post hoc non-parametric analysis was applied for between time-point comparisons.A constant relationship was found between the levels of Ig A in blood and saliva (r = 0.28; P = .031). No change in salivary IgA level was observed in the prednisone-only prephase, but it dropped significantly on day 22 (10.7+/-4.8 vs 9.6+/-6.4 vs 5.7+/-3.9 ng/mL; P = .04), when chemotherapy was given (anthracycline, vincristine, L-asparaginase).In blood, the total protein level decreased significantly between day 1 and 22 (6.2+/-0.4 vs 5.1+/-0.3 g/dL; P = .001). Lymphocyte count (per microliter) also decreased (2.12+/-0.8 vs 0.41+/-0.1 vs 1.08+/-0.5; P = .002). Four children suffered from oral mucositis graded 1 or higher between days 8 and 22.Chemotherapy given during the treatment of childhood ALL is associated with a reduction in the level of salivary immunoglobulin A. Prevention of the drop of salivary IgA may diminish the risk of occurrence of acute mucosal complications.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glucocorticoides/uso terapêutico , Imunoglobulina A Secretora/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Saliva/imunologia , Adolescente , Asparaginase/administração & dosagem , Proteínas Sanguíneas/análise , Criança , Pré-Escolar , Daunorrubicina/administração & dosagem , Feminino , Humanos , Contagem de Linfócitos , Masculino , Prednisona/uso terapêutico , Proteínas/análise , Indução de Remissão , Saliva/química , Estomatite/induzido quimicamente , Vincristina/administração & dosagem
7.
PLoS One ; 15(9): e0239235, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941548

RESUMO

New evidence on the COVID-19 pandemic is being published daily. Ongoing high-quality assessment of this literature is therefore needed to enable clinical practice to be evidence-based. This review builds on a previous scoping review and aimed to identify associations between disease severity and various clinical, laboratory and radiological characteristics. We searched MEDLINE, CENTRAL, EMBASE, Scopus and LILACS for studies published between January 1, 2019 and March 22, 2020. Clinical studies including ≥10 patients with confirmed COVID-19 of any study design were eligible. Two investigators independently extracted data and assessed risk of bias. A quality effects model was used for the meta-analyses. Subgroup analysis and meta-regression identified sources of heterogeneity. For hospitalized patients, studies were ordered by overall disease severity of each population and this order was used as the modifier variable in meta-regression. Overall, 86 studies (n = 91,621) contributed data to the meta-analyses. Severe disease was strongly associated with fever, cough, dyspnea, pneumonia, any computed tomography findings, any ground glass opacity, lymphocytopenia, elevated C-reactive protein, elevated alanine aminotransferase, elevated aspartate aminotransferase, older age and male sex. These variables typically increased in prevalence by 30-73% from mild/early disease through to moderate/severe disease. Among hospitalized patients, 30-78% of heterogeneity was explained by severity of disease. Elevated white blood cell count was strongly associated with more severe disease among moderate/severe hospitalized patients. Elevated lymphocytes, low platelets, interleukin-6, erythrocyte sedimentation rate and D-dimers showed potential associations, while fatigue, gastrointestinal symptoms, consolidation and septal thickening showed non-linear association patterns. Headache and sore throat were associated with the presence of disease, but not with more severe disease. In COVID-19, more severe disease is strongly associated with several clinical, laboratory and radiological characteristics. Symptoms and other variables in early/mild disease appear non-specific and highly heterogeneous. Clinical Trial Registration: PROSPERO CRD42020170623.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Adulto , Idoso , Biomarcadores , Contagem de Células Sanguíneas , Proteínas Sanguíneas/análise , Sedimentação Sanguínea , Terapia Combinada , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/terapia , Feminino , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/terapia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Avaliação de Sintomas
8.
Sci Rep ; 10(1): 16029, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994444

RESUMO

A large proportion of end-stage renal disease (ESRD) patients under long-term haemodialysis, have persistent anaemia and require high doses of recombinant human erythropoietin (rhEPO). However, the underlying mechanisms of renal anaemia have not been fully elucidated in these patients. In this study, we will be focusing on anaemia and plasma proteins in ESRD patients on high-flux haemodialysis (HF) and on-line haemodiafiltration (HDF), to investigate using two proteomic approaches if patients undergoing these treatments develop differences in their plasma protein composition and how this could be related to their anaemia. The demographic and biochemical data revealed that HDF patients had lower anaemia and much lower rhEPO requirements than HF patients. Regarding their plasma proteomes, HDF patients had increased levels of a protein highly similar to serotransferrin, trypsin-1 and immunoglobulin heavy constant chain alpha-1, and lower levels of alpha-1 antitrypsin, transthyretin, apolipoproteins E and C-III, and haptoglobin-related protein. Lower transthyretin levels in HDF patients were further confirmed by transthyretin-peptide quantification and western blot detection. Since ESRD patients have increased transthyretin, a protein that can aggregate and inhibit transferrin endocytosis and erythropoiesis, our finding that HDF patients have lower transthyretin and lower anaemia suggests that the decrease in transthyretin plasma levels would allow an increase in transferrin endocytosis, contributing to erythropoiesis. Thus, transthyretin could be a critical actor for anaemia in ESRD patients and a novel player for haemodialysis adequacy.


Assuntos
Anemia/tratamento farmacológico , Eritropoetina/administração & dosagem , Falência Renal Crônica/terapia , Pré-Albumina/metabolismo , Proteômica/métodos , Diálise Renal/classificação , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/etiologia , Proteínas Sanguíneas/análise , Cromatografia Líquida , Regulação para Baixo , Eritropoetina/uso terapêutico , Feminino , Hemodiafiltração/métodos , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Espectrometria de Massas em Tandem
9.
Biomed Khim ; 66(4): 294-316, 2020 Jul.
Artigo em Russo | MEDLINE | ID: mdl-32893820

RESUMO

The proteomic composition of a biological sample serves as the most important feature of a biological object, and it allows discriminating normal and pathological conditions. Targeted mass spectrometric analysis, namely, multiple reaction monitoring (MRM) using synthetic isotopically-labeled internal standard (SIS), is the main alternative to the ELISA method for the analysis of diagnostically significant proteins. Based on the MRM results, a prototype test system has been developed; it employs the targeted mass spectrometric method for multiplex, quantitative analysis of FDA-verified proteins in whole blood plasma. Using this approach, it was possible to measure the content of 42 proteins in 31 samples in a concentration range spanning five orders of magnitude. The interindividual variability for 30 of the 42 registered proteins was less than 40%. The largest scatter was observed for haptoglobin (68%), immunoglobulin heavy constant delta IGHD (90%), angiotensin (72%), sex hormone-binding globulin SHBG (100%) and lipoprotein-(a) (136%). The obtained results on the concentration of proteins correlate with published data (Hortin et al., 2008, Clinical Chemistry, 54, 1608) with R2=0.84. The developed prototype test system based on targeted mass spectrometric analysis of proteins can be considered as an alternative to methods using monoclonal antibodies.


Assuntos
Proteínas Sanguíneas , Proteínas , Proteômica , Proteínas Sanguíneas/análise , Ensaio de Imunoadsorção Enzimática , Voluntários Saudáveis , Humanos , Espectrometria de Massas
10.
PLoS One ; 15(9): e0238533, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966280

RESUMO

In this proof-of-concept study, we tested whether placebo effects can be monitored and predicted by plasma proteins. In a randomized controlled design, 90 participants were exposed to a nauseating stimulus on two separate days and were randomly allocated to placebo treatment or no treatment on the second day. Significant placebo effects on nausea, motion sickness, and (in females) gastric activity could be verified. Using label-free tandem mass spectrometry, 74 differentially regulated proteins were identified as correlates of the placebo effect. Gene ontology (GO) enrichment analyses identified acute-phase proteins and microinflammatory proteins to be involved, and the identified GO signatures predicted day-adjusted scores of nausea indices in the placebo group. We also performed GO enrichment analyses of specific plasma proteins predictable by the experimental factors or their interactions and identified 'grooming behavior' as a prominent hit. Finally, Receiver Operator Characteristics (ROC) allowed to identify plasma proteins differentiating placebo responders from non-responders, comprising immunoglobulins and proteins involved in oxidation reduction processes and complement activation. Plasma proteomics is a promising tool to identify molecular correlates and predictors of the placebo effect in humans.


Assuntos
Proteínas Sanguíneas/análise , Náusea/sangue , Náusea/terapia , Efeito Placebo , Terapia por Acupuntura , Adulto , Terapia por Estimulação Elétrica , Feminino , Humanos , Masculino , Enjoo devido ao Movimento/sangue , Enjoo devido ao Movimento/terapia , Proteômica , Adulto Jovem
11.
J Neuroimmunol ; 348: 577359, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32841722

RESUMO

Multiple sclerosis (MS) manifesting before age 18 years is defined as pediatric MS (pMS). We analysed plasma proteins in pMS by an untargeted proteomic approach. Patients with pMS (Group pMS, n = 33), patients with demyelinating disease not meeting pMS diagnostic criteria (unclassified demyelinating disease, Group U, n = 4) and age-matched healthy subjects (Group C, n = 40) were included. Plasma proteomic analysis was performed using Q-TOF LC/MS. Proteins having fold change >1.2 and found to be statistically different (p < 0.05) between the groups were identified and discussed with a clinical perspective. Group pMS had higher alpha 1B glycoprotein (A1BG), complement factor B (CFB), plasminogen (PLG), alpha-2-antiplasmin (α2-AP, SERPINF2), inter alpha trypsin inhibitor heavy chain H2 (ITIH2), and lower centrosomal protein of 290 (CEP290) and F-box/LRR-repeat protein 17 (FBXL17) concentrations than Group C. Measurements from Group U, whose definite diagnoses were established as pMS (n = 3) and myelin oligodendrocyte glycoprotein antibody-associated disease (n = 1) on follow-up after the study, were statistically close to the results of Group pMS. Plasma protein changes observed in our study were related to the inflammation, coagulation and oxidative stress pathways. If confirmed and validated in larger groups, these results may indicate potential biomarker(s) for demyelinating diseases at proteome level and could encourage studies for the development of novel diagnostic kits.


Assuntos
Biomarcadores/sangue , Esclerose Múltipla/sangue , Adolescente , Idade de Início , Proteínas Sanguíneas/análise , Criança , Feminino , Humanos , Masculino , Esclerose Múltipla/diagnóstico , Proteômica , Adulto Jovem
12.
Nat Commun ; 11(1): 3903, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764543

RESUMO

Top-down mass spectrometry (MS)-based proteomics provides a comprehensive analysis of proteoforms to achieve a proteome-wide understanding of protein functions. However, the MS detection of low-abundance proteins from blood remains an unsolved challenge due to the extraordinary dynamic range of the blood proteome. Here, we develop an integrated nanoproteomics method coupling peptide-functionalized superparamagnetic nanoparticles (NPs) with top-down MS for the enrichment and comprehensive analysis of cardiac troponin I (cTnI), a gold-standard cardiac biomarker, directly from serum. These NPs enable the sensitive enrichment of cTnI (<1 ng/mL) with high specificity and reproducibility, while simultaneously depleting highly abundant proteins such as human serum albumin (>1010 more abundant than cTnI). We demonstrate that top-down nanoproteomics can provide high-resolution proteoform-resolved molecular fingerprints of diverse cTnI proteoforms to establish proteoform-pathophysiology relationships. This scalable and reproducible antibody-free strategy can generally enable the proteoform-resolved analysis of low-abundance proteins directly from serum to reveal previously unachievable molecular details.


Assuntos
Análise Química do Sangue/métodos , Proteínas Sanguíneas/análise , Espectrometria de Massas/métodos , Proteômica/métodos , Troponina I/sangue , Biomarcadores/sangue , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Nanotecnologia , Processamento de Proteína Pós-Traducional , Proteoma/análise , Reprodutibilidade dos Testes , Albumina Sérica Humana/análise
13.
J Proteome Res ; 19(11): 4417-4427, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-32786691

RESUMO

Over 5 million people around the world have tested positive for the beta coronavirus SARS-CoV-2 as of May 29, 2020, a third of which are in the United States alone. These infections are associated with the development of a disease known as COVID-19, which is characterized by several symptoms, including persistent dry cough, shortness of breath, chills, muscle pain, headache, loss of taste or smell, and gastrointestinal distress. COVID-19 has been characterized by elevated mortality (over 100 thousand people have already died in the US alone), mostly due to thromboinflammatory complications that impair lung perfusion and systemic oxygenation in the most severe cases. While the levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) have been associated with the severity of the disease, little is known about the impact of IL-6 levels on the proteome of COVID-19 patients. The present study provides the first proteomics analysis of sera from COVID-19 patients, stratified by circulating levels of IL-6, and correlated to markers of inflammation and renal function. As a function of IL-6 levels, we identified significant dysregulation in serum levels of various coagulation factors, accompanied by increased levels of antifibrinolytic components, including several serine protease inhibitors (SERPINs). These were accompanied by up-regulation of the complement cascade and antimicrobial enzymes, especially in subjects with the highest levels of IL-6, which is consistent with an exacerbation of the acute phase response in these subjects. Although our results are observational, they highlight a clear increase in the levels of inhibitory components of the fibrinolytic cascade in severe COVID-19 disease, providing potential clues related to the etiology of coagulopathic complications in COVID-19 and paving the way for potential therapeutic interventions, such as the use of pro-fibrinolytic agents. Raw data for this study are available through ProteomeXchange with identifier PXD020601.


Assuntos
Proteínas Sanguíneas/análise , Proteínas do Sistema Complemento/análise , Infecções por Coronavirus , Interleucina-6/sangue , Pandemias , Pneumonia Viral , Proteoma/análise , Adulto , Betacoronavirus , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Feminino , Hemólise , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Proteômica
14.
J Environ Pathol Toxicol Oncol ; 39(2): 113-123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749121

RESUMO

Liver cancer or hepatocellular carcinoma is considered to be the third leading cause of death among all other cancers. The rate of liver cancer occurrence is high, and the rate of recovery is low. In this study, we investigated the therapeutic efficacy of vicenin-2 against the diethylnitrosamine-induced liver carcinoma in experimental rats. Diethylnitrosamine was widely employed as a carcinogenic agent to stimulate the cancer in animal models. Our results indicated that vicenin-2 administration effectively attenuates the diethylnitrosamine-induced physiological and pharmacological alterations in the experimental rats. Vicenin-2 treatment significantly enhanced the pathological lesions and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and α-fetoprotein (AFP) in serum. We also observed that vicenin-2 reduced the production of reactive oxygen species, decreased the liver weight, upregulated expression of apoptotic proteins, and decreased the histological changes in the liver, which are induced by the diethylnitrosamine in rats. Moreover, vicenin-2 downregulates antiapoptotic Bcl-2 and Bcl-xL, and upregulates the proapoptotic Bax and caspase. Hence, our results suggested that vicenin-2 had a highly therapeutic effect in reversing diethylnitrosamine-induced liver carcinoma in rats, which might be related to the apoptosis induced by vicenin-2. Therefore vicenin-2 could be a good candidate for future therapeutic use to inhibit chemically induced liver cancer.


Assuntos
Apigenina/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Glucosídeos/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biomarcadores Tumorais/sangue , Proteínas Sanguíneas/análise , Peso Corporal/efeitos dos fármacos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Dietilnitrosamina/toxicidade , Enzimas/sangue , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Soroglobulinas/análise
15.
Nature ; 583(7817): 596-602, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32669715

RESUMO

Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified-such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function1-these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis2-or 'Mouse Ageing Cell Atlas'-which follows on from the original Tabula Muris3. We reveal linear and nonlinear shifts in gene expression during ageing, with the associated genes clustered in consistent trajectory groups with coherent biological functions-including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Notably, these gene sets show similar expression across tissues, differing only in the amplitude and the age of onset of expression. Widespread activation of immune cells is especially pronounced, and is first detectable in white adipose depots during middle age. Single-cell RNA sequencing confirms the accumulation of T cells and B cells in adipose tissue-including plasma cells that express immunoglobulin J-which also accrue concurrently across diverse organs. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing, providing a foundation from which to track systemic sources of declining health at old age.


Assuntos
Envelhecimento/genética , Envelhecimento/fisiologia , Regulação da Expressão Gênica , Especificidade de Órgãos/genética , Animais , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/genética , Feminino , Cadeias J de Imunoglobulina/genética , Cadeias J de Imunoglobulina/metabolismo , Masculino , Camundongos , Plasmócitos/citologia , Plasmócitos/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/genética , RNA-Seq , Análise de Célula Única , Linfócitos T/citologia , Linfócitos T/metabolismo , Fatores de Tempo , Transcriptoma
16.
Cell Syst ; 11(1): 11-24.e4, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32619549

RESUMO

The COVID-19 pandemic is an unprecedented global challenge, and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high-throughput serum and plasma proteomics that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories. Our low-cost workflow handles up to 180 samples per day, enables high precision quantification, and reduces batch effects for large-scale and longitudinal studies. We use our platform on samples collected from a cohort of early hospitalized cases of the SARS-CoV-2 pandemic and identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. In total, this work supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.


Assuntos
Proteínas Sanguíneas/metabolismo , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Proteômica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Infecções por Coronavirus/classificação , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/classificação , Pneumonia Viral/classificação , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Adulto Jovem
17.
Sci Rep ; 10(1): 12415, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709962

RESUMO

Obesity is a chronic disease that negatively affects life expectancy through its association with life-threatening diseases such as cancer and cardiovascular diseases. Expression proteomics combined with in silico interaction studies are used to uncover potential biomarkers and the pathways that promote obesity-related complications. These biomarkers can either aid in the development of personalized therapies or identify individuals at risk of developing obesity-related diseases. To determine the serum protein changes, Wistar rats were fed standard chow (low fat, LF), or chow formulated high fat (HF) diets (HF1, HF2 and HF3) for 8 and 42 weeks to induce obesity. Serum samples were collected from lean and obese rats at these time points. The serum samples were precipitated using trichloroacetic acid (TCA)/acetone and analyzed by 2-Dimensional SDS-PAGE. Serum protein profiles were examined using mass spectrometry (MS)-based proteomics and validated by western blotting. Protein-protein interactions among the selected proteins were studied in silico using bioinformatics tools. Several proteins showed differences in expression among the three HF diets when compared to the LF diet, and only proteins with ≥ twofold expression levels were considered differentially expressed. Apolipoprotein-AIV (APOA4), C-reactive protein (CRP), and alpha 2-HS glycoprotein (AHSG) showed differential expression at both 8 and 42 weeks, whereas alpha 1 macroglobulin (AMBP) was differentially expressed only at 8 weeks. Network analysis revealed some interactions among the proteins, an indication that these proteins might interactively play a crucial role in development of obesity-induced diseases. These data show the variation in the expression of serum proteins during acute and chronic exposure to high fat diet. Based on the expression and the in-silico interaction these proteins warrant further investigation for their role in obesity development.


Assuntos
Proteínas Sanguíneas/metabolismo , Obesidade/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Proteínas Sanguíneas/análise , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Masculino , Obesidade/sangue , Obesidade/complicações , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteômica , Ratos , Fatores de Risco
18.
Bioanalysis ; 12(13): 919-935, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32686955

RESUMO

Aim: Evaluation of a novel microsampling device for its use in clinical sample collection and biomarker analysis. Methodology: Matching samples were collected from 16 healthy donors (ten females, six males; age 42 ± 20) via K2EDTA touch activated phlebotomy (TAP) device and phlebotomy. The protein profile differences between sampling groups was evaluated using aptamer-based proteomic assay SomaScan and selected ELISA. Conclusion: Somascan signal concordance between phlebotomy- and TAP-generated samples was studied and comparability of protein abundances between these blood sample collection methods was demonstrated. Statistically significant correlation in selected ELISA assays also confirmed the TAP device applicability to the quantitative analysis of protein biomarkers in clinical trials.


Assuntos
Proteínas Sanguíneas/análise , Flebotomia/instrumentação , Adulto , Biomarcadores/sangue , Ensaios Clínicos como Assunto , Infecções por Coronavirus/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Hemólise , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Proteômica/instrumentação , Adulto Jovem
19.
Clin Appl Thromb Hemost ; 26: 1076029620943671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702995

RESUMO

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.


Assuntos
Afro-Americanos , Betacoronavirus , Infecções por Coronavirus/etnologia , Pandemias , Pneumonia Viral/etnologia , Trombofilia/etnologia , Tromboembolia Venosa/etnologia , Afro-Americanos/genética , Anemia Falciforme/sangue , Anemia Falciforme/etnologia , Anticoagulantes/uso terapêutico , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/genética , Ensaios Clínicos como Assunto , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Fator VIII/análise , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Estudos de Associação Genética , Predisposição Genética para Doença , Disparidades em Assistência à Saúde , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Seleção de Pacientes , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Polimorfismo de Nucleotídeo Único , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etnologia , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
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