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1.
Front Immunol ; 12: 659419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079547

RESUMO

Highly pathogenic virus infections usually trigger cytokine storms, which may have adverse effects on vital organs and result in high mortalities. The two cytokines interleukin (IL)-4 and interferon (IFN)-γ play key roles in the generation and regulation of cytokine storms. However, it is still unclear whether the cytokine with the largest induction amplitude is the same under different virus infections. It is unknown which is the most critical and whether there are any mathematical formulas that can fit the changing rules of cytokines. Three coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2), three influenza viruses (2009H1N1, H5N1 and H7N9), Ebola virus, human immunodeficiency virus, dengue virus, Zika virus, West Nile virus, hepatitis B virus, hepatitis C virus, and enterovirus 71 were included in this analysis. We retrieved the cytokine fold change (FC), viral load, and clearance rate data from these highly pathogenic virus infections in humans and analyzed the correlations among them. Our analysis showed that interferon-inducible protein (IP)-10, IL-6, IL-8 and IL-17 are the most common cytokines with the largest induction amplitudes. Equations were obtained: the maximum induced cytokine (max) FC = IFN-γ FC × (IFN-γ FC/IL-4 FC) (if IFN-γ FC/IL-4 FC > 1); max FC = IL-4 FC (if IFN-γ FC/IL-4 FC < 1). For IFN-γ-inducible infections, 1.30 × log2 (IFN-γ FC) = log10 (viral load) - 2.48 - 2.83 × (clearance rate). The clinical relevance of cytokines and their antagonists is also discussed.


Assuntos
Síndrome da Liberação de Citocina/imunologia , Citocinas/sangue , Modelos Imunológicos , Viroses/complicações , Biomarcadores/sangue , Biomarcadores/metabolismo , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/virologia , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Carga Viral/imunologia , Viroses/sangue , Viroses/imunologia , Viroses/virologia
2.
Viruses ; 13(6)2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064104

RESUMO

Patients with coronavirus disease 2019 (COVID-19) predominantly have a respiratory tract infection with various symptoms and high mortality is associated with respiratory failure second to severe disease. The risk factors leading to severe disease remain unclear. Here, we reanalyzed a published single-cell RNA-Seq (scRNA-Seq) dataset and found that bronchoalveolar lavage fluid (BALF) of patients with severe disease compared to those with mild disease contained decreased TH17-type cells, decreased IFNA1-expressing cells with lower expression of toll-like receptor 7 (TLR7) and TLR8, increased IgA-expressing B cells, and increased hyperactive epithelial cells (and/or macrophages) expressing matrix metalloproteinases (MMPs), hyaluronan synthase 2 (HAS2), and plasminogen activator inhibitor-1 (PAI-1), which may together contribute to the pulmonary pathology in severe COVID-19. We propose IFN-I (and TLR7/TLR8) and PAI-1 as potential biomarkers to predict the susceptibility to severe COVID-19.


Assuntos
COVID-19/patologia , Pulmão/patologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/imunologia , COVID-19/imunologia , COVID-19/metabolismo , Bases de Dados Genéticas , Humanos , Hialuronan Sintases/metabolismo , Imunoglobulina A/metabolismo , Interferon-alfa/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Metaloproteinases da Matriz/metabolismo , Mucina-1/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , RNA-Seq , SARS-CoV-2 , Células Th17/metabolismo , Células Th17/patologia
3.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065959

RESUMO

Brain tissue may be especially sensitive to electromagnetic phenomena provoking signs of neural stress in cerebral activity. Fifty-four adult female Sprague-Dawley rats underwent ELISA and immunohistochemistry testing of four relevant anatomical areas of the cerebrum to measure biomarkers indicating induction of heat shock protein 70 (HSP-70), glucocorticoid receptors (GCR) or glial fibrillary acidic protein (GFAP) after single or repeated exposure to 2.45 GHz radiation in the experimental set-up. Neither radiation regime caused tissue heating, so thermal effects can be ruled out. A progressive decrease in GCR and HSP-70 was observed after acute or repeated irradiation in the somatosensory cortex, hypothalamus and hippocampus. In the limbic cortex; however, values for both biomarkers were significantly higher after repeated exposure to irradiation when compared to control animals. GFAP values in brain tissue after irradiation were not significantly different or were even lower than those of nonirradiated animals in all brain regions studied. Our results suggest that repeated exposure to 2.45 GHz elicited GCR/HSP-70 dysregulation in the brain, triggering a state of stress that could decrease tissue anti-inflammatory action without favoring glial proliferation and make the nervous system more vulnerable.


Assuntos
Cérebro/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Receptores de Glucocorticoides/metabolismo , Animais , Biomarcadores/metabolismo , Cérebro/efeitos da radiação , Feminino , Regulação da Expressão Gênica/efeitos da radiação , Hipocampo/metabolismo , Hipocampo/efeitos da radiação , Hipotálamo/metabolismo , Hipotálamo/efeitos da radiação , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/metabolismo , Córtex Somatossensorial/efeitos da radiação
4.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065977

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor, and macrophages account for 30-40% of its composition. Most of these macrophages derive from bone marrow monocytes playing a crucial role in tumor progression. Unraveling the mechanisms of macrophages-GBM crosstalk in an appropriate model will contribute to the development of specific and more successful therapies. We investigated the interaction of U87MG human GBM cells with primary human CD14+ monocytes or the THP-1 cell line with the aim of establishing a physiologically relevant heterotypic culture model. METHODS: primary monocytes and THP-1 cells were cultured in the presence of U87MG conditioned media or co-cultured together with previously formed GBM spheroids. Monocyte differentiation was determined by flow cytometry. RESULTS: primary monocytes differentiate to M2 macrophages when incubated with U87MG conditioned media in 2-dimensional culture, as determined by the increased percentage of CD14+CD206+ and CD64+CD206+ populations in CD11b+ cells. Moreover, the mitochondrial protein p32/gC1qR is expressed in monocytes exposed to U87MG conditioned media. When primary CD14+ monocytes or THP-1 cells are added to previously formed GBM spheroids, both invade and establish within them. However, only primary monocytes differentiate and acquire a clear M2 phenotype characterized by the upregulation of CD206, CD163, and MERTK surface markers on the CD11b+CD14+ population and induce alterations in the sphericity of the cell cultures. CONCLUSION: our results present a new physiologically relevant model to study GBM/macrophage interactions in a human setting and suggest that both soluble GBM factors, as well as cell-contact dependent signals, are strong inducers of anti-inflammatory macrophages within the tumor niche.


Assuntos
Neoplasias Encefálicas/metabolismo , Técnicas de Cocultura/métodos , Glioblastoma/metabolismo , Macrófagos/citologia , Monócitos/citologia , Biomarcadores/metabolismo , Proteínas de Transporte/metabolismo , Comunicação Celular , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/farmacologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Proteínas Mitocondriais/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Cultura Primária de Células , Esferoides Celulares/citologia , Esferoides Celulares/metabolismo , Células THP-1
5.
Ann Lab Med ; 41(6): 540-548, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34108281

RESUMO

During a severe infection such as coronavirus disease 2019 (COVID-19), the level of almost all analytes can change, presenting a correlation with disease severity and survival; however, a biomarker cannot be translated into clinical practice for treatment guidance until it is proven to have a significant impact. Several studies have documented the association between COVID-19 severity and circulating levels of C-reactive protein (CRP) and interleukin-6, and the accuracy of the CRP level in predicting treatment responses has been evaluated. Moreover, promising findings on prothrombin and D-dimer have been reported. However, the clinical usefulness of these biomarkers in COVID-19 is far from proven. The burst of data generation during this pandemic has led to the publication of numerous studies with several notable drawbacks, weakening the strength of their findings. We provide an overview of the key findings of studies on biomarkers for the prognosis and treatment response in COVID-19 patients. We also highlight the main drawbacks of these studies that have limited the clinical use of these biomarkers.


Assuntos
Biomarcadores/análise , COVID-19/patologia , Biomarcadores/metabolismo , Proteína C-Reativa/análise , COVID-19/terapia , COVID-19/virologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Interleucina-6/análise , MicroRNAs/metabolismo , Prognóstico , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
6.
Biomed Environ Sci ; 34(5): 356-363, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34059172

RESUMO

Objective: This study aimed to investigate the effects of N,N-dimethylglycine (DMG) on the concentration and metabolism of plasma homocysteine (pHcy) in folate-sufficient and folate-deficient rats. Methods: In this study, 0.1% DMG was supplemented in 20% casein diets that were either folate-sufficient (20C) or folate-deficient (20CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system. Results: Folate deprivation significantly increased pHcy concentration in rats fed 20C diet (from 14.19 ± 0.39 µmol/L to 28.49 ± 0.50 µmol/L; P < 0.05). When supplemented with DMG, pHcy concentration was significantly decreased (12.23 ± 0.18 µmol/L) in rats fed 20C diet but significantly increased (31.56 ± 0.59 µmol/L) in rats fed 20CFD. The hepatic methionine synthase activity in the 20CFD group was significantly lower than that in the 20C group; enzyme activity was unaffected by DMG supplementation regardless of folate sufficiency. The activity of hepatic cystathionine ß-synthase (CBS) in the 20CFD group was decreased but not in the 20C group; DMG supplementation enhanced hepatic CBS activity in both groups, in which the effect was significant in the 20C group but not in the other group. Conclusion: DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration.


Assuntos
Dieta , Suplementos Nutricionais , Deficiência de Ácido Fólico/metabolismo , Homocisteína/metabolismo , Sarcosina/análogos & derivados , Animais , Biomarcadores/metabolismo , Cromatografia Líquida , Fígado/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Sarcosina/administração & dosagem , Sarcosina/metabolismo
7.
Int J Mol Sci ; 22(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064456

RESUMO

Primary Sjögren's syndrome (pSS) is a complex heterogeneous disease characterized by a wide spectrum of glandular and extra-glandular manifestations. In this pilot study, a SWATH-MS approach was used to monitor extracellular vesicles-enriched saliva (EVs) sub-proteome in pSS patients, to compare it with whole saliva (WS) proteome, and assess differential expressed proteins between pSS and healthy control EVs samples. Comparison between EVs and WS led to the characterization of compartment-specific proteins with a moderate degree of overlap. A total of 290 proteins were identified and quantified in EVs from healthy and pSS patients. Among those, 121 proteins were found to be differentially expressed in pSS, 82% were found to be upregulated, and 18% downregulated in pSS samples. The most representative functional pathways associated to the protein networks were related to immune-innate response, including several members of S100 protein family, annexin A2, resistin, serpin peptidase inhibitors, azurocidin, and CD14 monocyte differentiation antigen. Our results highlight the usefulness of EVs for the discovery of novel salivary-omic biomarkers and open novel perspectives in pSS for the identification of proteins of clinical relevance that could be used not only for the disease diagnosis but also to improve patients' stratification and treatment-monitoring. Data are available via ProteomeXchange with identifier PXD025649.


Assuntos
Vesículas Extracelulares/metabolismo , Redes Reguladoras de Genes , Proteoma/genética , Saliva/metabolismo , Síndrome de Sjogren/genética , Adulto , Idoso , Anexina A2/genética , Anexina A2/metabolismo , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Biomarcadores/metabolismo , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Estudos de Casos e Controles , Vesículas Extracelulares/química , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Projetos Piloto , Mapeamento de Interação de Proteínas , Proteoma/classificação , Proteoma/metabolismo , Proteômica/instrumentação , Proteômica/métodos , Resistina/genética , Resistina/metabolismo , Proteínas S100/genética , Proteínas S100/metabolismo , Saliva/química , Serpinas/genética , Serpinas/metabolismo , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/metabolismo , Síndrome de Sjogren/patologia
8.
Biomolecules ; 11(5)2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066385

RESUMO

SARS-CoV-2 is a member of the family of coronaviruses associated with severe outbreaks of respiratory diseases in recent decades and is the causative agent of the COVID-19 pandemic. The recognition by and activation of the innate immune response recruits neutrophils, which, through their different mechanisms of action, form extracellular neutrophil traps, playing a role in infection control and trapping viral, bacterial, and fungal etiological agents. However, in patients with COVID-19, activation at the vascular level, combined with other cells and inflammatory mediators, leads to thrombotic events and disseminated intravascular coagulation, thus leading to a series of clinical manifestations in cerebrovascular, cardiac, pulmonary, and kidney disease while promoting severe disease and mortality. Previous studies of hospitalized patients with COVID-19 have shown that elevated levels of markers specific for NETs, such as free DNA, MPO, and H3Cit, are strongly associated with the total neutrophil count; with acute phase reactants that include CRP, D-dimer, lactate dehydrogenase, and interleukin secretion; and with an increased risk of severe COVID-19. This study analyzed the interactions between NETs and the activation pathways involved in immunothrombotic processes in patients with COVID-19.


Assuntos
COVID-19/patologia , Armadilhas Extracelulares/metabolismo , Trombose/imunologia , Trombose/patologia , Biomarcadores/metabolismo , COVID-19/imunologia , COVID-19/virologia , Proteínas do Sistema Complemento/metabolismo , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/patologia , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/patologia , Humanos , Neutrófilos/citologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , SARS-CoV-2/isolamento & purificação , Trombose/metabolismo
9.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067072

RESUMO

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman's correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.


Assuntos
COVID-19/sangue , Galectinas/sangue , Osteopontina/sangue , Pneumonia/sangue , Síndrome Respiratória Aguda Grave/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores/metabolismo , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Feminino , Humanos , Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Rim/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/tratamento farmacológico , Pneumonia/virologia , Curva ROC , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Adulto Jovem
10.
Int J Mol Sci ; 22(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34073119

RESUMO

Cells convey information among one another. One instrument employed to transmit data and constituents to specific (target) cells is extracellular vesicles (EVs). They originate from a variety of cells (endothelial, immune cells, platelets, mesenchymal stromal cells, etc.), and consequently, their surface characteristics and cargo vary according to the paternal cell. The cargo could be DNA, mRNA, microRNA, receptors, metabolites, cytoplasmic proteins, or pathological molecules, as a function of which EVs exert different effects upon endocytosis in recipient cells. Recently, EVs have become important participants in a variety of pathologies, including atherogenesis and coronavirus disease 2019 (COVID-19)-associated thrombosis. Herein, we summarize recent advances and some of our own results on the role of EVs in atherosclerotic cardiovascular diseases, and discuss their potential to function as signaling mediators, biomarkers and therapeutic agents. Since COVID-19 patients have a high rate of thrombotic events, a special section of the review is dedicated to the mechanism of thrombosis and the possible therapeutic potential of EVs in COVID-19-related thrombosis. Yet, EV mechanisms and their role in the transfer of information between cells in normal and pathological conditions remain to be explored.


Assuntos
Aterosclerose/metabolismo , COVID-19/metabolismo , Vesículas Extracelulares/metabolismo , Trombose/metabolismo , Aterosclerose/fisiopatologia , Aterosclerose/terapia , Aterosclerose/virologia , Biomarcadores/metabolismo , COVID-19/complicações , COVID-19/fisiopatologia , COVID-19/terapia , Células Endoteliais/metabolismo , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/virologia , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais/imunologia , Trombose/complicações , Trombose/fisiopatologia , Trombose/virologia
11.
Nat Commun ; 12(1): 3447, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103494

RESUMO

Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women.


Assuntos
Sistema Cardiovascular/embriologia , Embrião de Mamíferos/patologia , Ferro/deficiência , Animais , Aorta Torácica/anormalidades , Biomarcadores/metabolismo , Diferenciação Celular , Vasos Coronários/embriologia , Vasos Coronários/patologia , Suplementos Nutricionais , Edema/patologia , Embrião de Mamíferos/anormalidades , Desenvolvimento Embrionário , Feminino , Perfilação da Expressão Gênica , Interação Gene-Ambiente , Proteínas de Fluorescência Verde/metabolismo , Ferro/metabolismo , Vasos Linfáticos/embriologia , Vasos Linfáticos/patologia , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Penetrância , Fenótipo , Gravidez , Transdução de Sinais , Células-Tronco/patologia , Transgenes , Tretinoína/metabolismo
12.
Int J Mol Sci ; 22(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064267

RESUMO

Sustainability of aquaculture is tied to the origin of feed ingredients. In search of sustainable fish meal-free formulations for rainbow trout, we evaluated the effect of Hermetia illucens meal (H) and poultry by-product meal (P), singly (10, 30, and 60% of either H or P) or in combination (10% H + 50% P, H10P50), as partial replacement of vegetable protein (VM) on gut microbiota (GM), inflammatory, and immune biomarkers. Fish fed the mixture H10P50 had the best growth performance. H, P, and especially the combination H10P50 partially restored α-diversity that was negatively affected by VM. Diets did not differ in the Firmicutes:Proteobacteria ratio, although the relative abundance of Gammaproteobacteria was reduced in H and was higher in P and in the fishmeal control. H had higher relative abundance of chitin-degrading Actinomyces and Bacillus, Dorea, and Enterococcus. Actinomyces was also higher in H feed, suggesting feed-chain microbiome transmission. P increased the relative abundance of protein degraders Paeniclostridium and Bacteroidales. IL-1ß, IL-10, TGF-ß, COX-2, and TCR-ß gene expression in the midgut and head kidney and plasma lipopolysaccharide (LPS) revealed that the diets did not compromise the gut barrier function or induce inflammation. H, P, and H10P50 therefore appear valid protein sources in fishmeal-free aquafeeds.


Assuntos
Proteínas Animais da Dieta/metabolismo , Biomarcadores/metabolismo , Microbioma Gastrointestinal/fisiologia , Inflamação/metabolismo , Oncorhynchus mykiss/metabolismo , Oncorhynchus mykiss/microbiologia , Ração Animal , Animais , Aquicultura/métodos , Dieta/métodos , Rim Cefálico/metabolismo , Insetos/metabolismo , Aves Domésticas/metabolismo , Produtos Avícolas
13.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066951

RESUMO

Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer's disease (AD) and Parkinson's disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.


Assuntos
Doença de Alzheimer/patologia , Doenças de Pequenos Vasos Cerebrais/patologia , Esclerose Múltipla/patologia , Degeneração Neural/patologia , Doença de Parkinson/patologia , Doença de Alzheimer/fisiopatologia , Animais , Biomarcadores/metabolismo , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Humanos , Esclerose Múltipla/fisiopatologia , Degeneração Neural/fisiopatologia , Doença de Parkinson/fisiopatologia
14.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067001

RESUMO

Investigations into the mechanisms regulating obesity are frantic and novel translational approaches are needed. The raccoon dog (Nyctereutes procyonoides) is a canid species representing a promising model to study metabolic regulation in a species undergoing cycles of seasonal obesity and fasting. To understand the molecular mechanisms of metabolic regulation in seasonal adaptation, we analyzed key central nervous system and peripheral signals regulating food intake and metabolism from raccoon dogs after autumnal fattening and winter fasting. Expressions of neuropeptide Y (NPY), orexin-2 receptor (OX2R), pro-opiomelanocortin (POMC) and leptin receptor (ObRb) were analyzed as examples of orexigenic and anorexigenic signals using qRT-PCR from raccoon dog hypothalamus samples. Plasma metabolic profiles were measured with 1H NMR-spectroscopy and LC-MS. Circulating hormones and cytokines were determined with canine specific antibody assays. Surprisingly, NPY and POMC were not affected by the winter fasting nor autumn fattening and the metabolic profiles showed a remarkable equilibrium, indicating conserved homeostasis. However, OX2R and ObRb expression changes suggested seasonal regulation. Circulating cytokine levels were not increased, demonstrating that the autumn fattening did not induce subacute inflammation. Thus, the raccoon dog developed seasonal regulatory mechanisms to accommodate the autumnal fattening and prolonged fasting making the species unique in coping with the extreme environmental challenges.


Assuntos
Adiposidade , Jejum/metabolismo , Metaboloma , Cães Guaxinins/metabolismo , Estações do Ano , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/patologia , Animais , Biomarcadores/metabolismo , Peso Corporal , Análise Discriminante , Feminino , Hormônios/sangue , Hipotálamo/metabolismo , Inflamação/patologia , Análise dos Mínimos Quadrados , Limite de Detecção , Análise Multivariada , Peptídeos/genética , Peptídeos/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Cães Guaxinins/sangue , Receptores de Peptídeos/metabolismo
15.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067060

RESUMO

Recent findings suggest that epithelial to mesenchymal transition (EMT), a key step during heart development, is involved in cardiac tissue repair following myocardial infarction (MI). MicroRNAs (miRNAs) act as key regulators in EMT processes; however, the mechanisms by which miRNAs target epicardial EMT remain largely unknown. Here, by using an in vitro model of epicardial EMT, we investigated the role of miRNAs as regulators of this process and their potential targets. EMT was induced in murine epicardial-mesothelial cells (EMCs) through TGF ß1 treatment for 48, 72, and 96 h as indicated by the expression of EMT-related genes by qRT-PCR, WB, and immunofluorescence. Further, enhanced expression of stemness genes was also detected. Among several EMT-related miRNAs, miR-200c-3p expression resulted as the most strongly suppressed. Interestingly, we also found a significant upregulation of Follistatin-related protein 1 (FSTL1), a miR-200c predicted target already identified as a potent cardiogenic factor produced by epicardial cells that promotes regeneration following MI. Dual-luciferase reporter assay demonstrated that miR-200c-3p directly targeted the 3'-untranslated region of FSTL1 in EMCs. Consistently, WB analysis showed that knockdown of miR-200c-3p significantly increased FSTL1 expression, whereas overexpression of miR-200c-3p counteracted TGF ß1-mediated FSTL1 upregulation. Importantly, FSTL1 silencing maintained epithelial features in EMCs, despite EMT induction by TGF ß1, and attenuated EMT-associated traits, including migration and stemness. In conclusion, epicardial FSTL1, an important cardiogenic factor in its secreted form, induces EMT, stemness, and migration of EMCs in a miR-200c-3p dependent pathway.


Assuntos
Transição Epitelial-Mesenquimal , Epitélio/metabolismo , Proteínas Relacionadas à Folistatina/metabolismo , MicroRNAs/metabolismo , Pericárdio/patologia , Animais , Biomarcadores/metabolismo , Transição Epitelial-Mesenquimal/genética , Feminino , Mesoderma/patologia , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fator de Crescimento Transformador beta1/farmacologia
16.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067156

RESUMO

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.


Assuntos
Asma/metabolismo , Vesículas Extracelulares/metabolismo , Animais , Asma/genética , Asma/microbiologia , Asma/fisiopatologia , Biomarcadores/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos
17.
Med Sci Monit ; 27: e930688, 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33934098

RESUMO

BACKGROUND Influenza-associated acute necrotizing encephalopathy (IANE) can be lethal and disabling and have a sudden onset and deteriorate rapidly but lacks early diagnostic indicators. We aimed to examine the early clinical diagnostic indicators in children with IANE. MATERIAL AND METHODS Acute influenza patients were grouped according to their clinical manifestations: flu alone (FA), flu with febrile seizure (FS), influenza-associated encephalopathy (IAE), and IANE. The clinical features, biomarkers, neuroelectrophysiological results, and neuroimaging examination results were compared. RESULTS A total of 31 patients were included (FA (n=4), FS (n=8), IAE (n=14), and IANE (n=5)). The IANE group, whose mean age was 3.7 years, was more likely to show rapid-onset seizure, acute disturbance of consciousness (ADOC), Babinski's sign, and death/sequela. More patients in the IANE group required tracheal intubation mechanical ventilation and received intravenous immunoglobulins (IVIG) and glucocorticoids. The alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels in the IANE group were significantly higher than in the FS and IAE groups. The aquaporin-4 (AQP-4) antibody and malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) were notably higher in IANE patients in the acute stage compared with FS and IAE patients. All patients in the IANE group had positive neuroimaging findings. CONCLUSIONS Early clinical warning factors for IANE include rapid-onset seizures in patients under 4 years of age, ADOC, and pathological signs. Increased AQP-4 antibodies and MDA levels in CSF might contribute to early diagnosis. Early magnetic resonance venography (MRV) and susceptibility-weighted imaging (SWI) sequences, or thrombelastography to identify deep vein thrombosis, might indicate clinical deterioration.


Assuntos
Encefalopatias/diagnóstico , Influenza Humana/diagnóstico , Doença Aguda , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Aquaporinas/sangue , Aquaporinas/metabolismo , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Encefalopatias/sangue , Encefalopatias/metabolismo , Líquido Cefalorraquidiano/metabolismo , Pré-Escolar , Feminino , Glucocorticoides/sangue , Glucocorticoides/metabolismo , Humanos , Imunoglobulinas Intravenosas/sangue , Imunoglobulinas Intravenosas/metabolismo , Influenza Humana/sangue , Influenza Humana/metabolismo , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Neuroimagem/métodos , Convulsões/sangue , Convulsões/diagnóstico , Convulsões/metabolismo
18.
Medicine (Baltimore) ; 100(21): e25808, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032694

RESUMO

ABSTRACT: MicroRNAs play important roles in gestational diabetes mellitus (GDM), and this study aimed to elucidate the clinical significance of miR-96-5p in diagnosing GDM.There are 123 pregnant women diagnosed with GDM and 123 healthy pregnant women were enrolled as control participants. Placenta and plasma samples from the patients and control participants were collected, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to determine miR-96-5p expression levels. Moreover, a receiver operating characteristic (ROC) curve was established to evaluate the significance of miR-96-5p in diagnosing GDM. HRT-8/SVneo trophoblasts were cultured under high glucose conditions and treated with miR-96-5p mimics, and cell viability was examined.miR-96-5p levels were significantly decreased in both the placenta and plasma samples of patients with GDM. The ROC curve indicated that miR-96-5p can serve as a diagnostic biomarker for GDM with high sensitivity and specificity. Moreover, miR-96-5p levels were markedly low under high glucose conditions, and the overexpression of miR-96-5p increased the viability, respectively, of trophoblasts in vitro.miR-96-5p may participate in the pathogenesis of GDM by exerting effects on the viability of trophoblasts.


Assuntos
Diabetes Gestacional/diagnóstico , MicroRNAs/análise , Adulto , Biomarcadores/análise , Biomarcadores/metabolismo , Glicemia/análise , Estudos de Casos e Controles , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura/metabolismo , Diabetes Gestacional/sangue , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , MicroRNAs/agonistas , MicroRNAs/metabolismo , Placenta/patologia , Gravidez , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trofoblastos
19.
Medicine (Baltimore) ; 100(21): e26036, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032726

RESUMO

BACKGROUND: As a gynecological disease, endometriosis (EM) seriously endangers the health of women at the age of childbearing and is closely related to long noncoding RNAs (lncRNAs). Current studies have discovered that there are differential expressions of many kinds of lncRNAs in EM. However, whether lncRNAs can be applied as a new marker for the prediction of the recurrence of EM is still controversial. In this study, meta-analysis and bioinformatics analysis were carried out to explore the value of lncRNAs as a predictor of the recurrence of EM and to analyze its biological role. METHODS: PubMed, Embase, and Web of Science databases were searched through computer and the articles published from the self-built database to April 2021 were collected. According to the inclusion and exclusion criteria, the literature was screened, and the quality of the inclusion study was evaluated. Stata 16.0 software was used for meta-analysis. The co-expression genes related to lncRNAs were screened by online tool Co-LncRNA. Then David for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were conducted. A competitive endogenous RNA network that may exist in lncRNAs through Starbase was built. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: This meta-analysis could provide high-quality evidence support for lncRNAs, so as to predict the recurrence of EM. At the same time, we use bioinformatics technology to predict and analyze its biological effects, which provides a theoretical basis for further experimental verification. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/MF3QJ.


Assuntos
Endometriose/diagnóstico , Redes Reguladoras de Genes , RNA Longo não Codificante/análise , Biomarcadores/análise , Biomarcadores/metabolismo , Biologia Computacional , Endometriose/genética , Endometriose/patologia , Endometriose/cirurgia , Endométrio/patologia , Endométrio/cirurgia , Feminino , Humanos , Metanálise como Assunto , RNA Longo não Codificante/metabolismo , Recidiva
20.
Medicine (Baltimore) ; 100(21): e26153, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032772

RESUMO

ABSTRACT: Although the incidence is lower in men than women, osteoporosis remains a significant health issue in men as it may give rise to severe complications if not managed appropriately. As men and women show different biological and social backgrounds, we retrospectively evaluated the differences in the bone metabolism between men and women using bone biomarkers.Bone mineral density (BMD) was determined in all patients using dual-energy X-ray absorptiometry (DXA) and analyzing various bone biomarkers such as carboxyl-terminal collagen crosslinks (CTX), osteocalcin (OCT), and alkaline phosphatase (ALP). The CTX/OCT ratio was used to estimate the association between bone absorption and formation.OCT, CTX, and ALP levels were elevated in patients with osteoporosis. Women displayed a higher incidence of osteoporosis and greater reduction in BMD than men. The mean OCT level in men was lower than that in women. Moreover, men showed significantly lower OCT levels than women of aged 65 and under 80 years old. Among patients with osteoporosis, men had a higher ratio of bone markers than women.Levels of biomarkers of bone formation and absorption were increased in the osteoporosis group. However, men showed lower increases in bone formation biomarkers than did women, indicating that the rate of bone formation relative to bone absorption did not increase in men compared with that in women. Therefore, we suggest that men and women have different bone metabolism in old age.


Assuntos
Osso e Ossos/metabolismo , Osteoporose/metabolismo , Caracteres Sexuais , Absorciometria de Fóton , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Densidade Óssea , Reabsorção Óssea , Osso e Ossos/diagnóstico por imagem , Feminino , Humanos , Masculino , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteoclastos/metabolismo , Osteogênese , Osteoporose/diagnóstico por imagem , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Estudos Retrospectivos
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