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1.
Medicine (Baltimore) ; 99(1): e18596, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895808

RESUMO

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Because the molecular mechanisms of DKD are not fully understood, exploration of hub genes and the mechanisms underlying this disease are essential for elucidating the pathogenesis and progression of DKD. Accordingly, in this study, we performed an analysis of gene expression in DKD. The differentially expressed genes (DEGs) included 39 upregulated genes and 113 downregulated genes in the GSE30528 dataset and 127 upregulated genes and 18 downregulated genes in the GSE30529 dataset. Additionally, functional analyses were performed to determine the roles of DEGs using glomeruli samples from patients with DKD and healthy controls from the GSE30528 dataset and using tubule samples from patients with DKD and healthy controls from the GSE30529 dataset. These DEGs were enriched in pathways such as the Wnt signaling pathway, metabolic pathways, and the mammalian target of rapamycin signaling pathway in the GSE30528 dataset and the longevity regulating pathway and Ras signaling pathway in the GSE30529 dataset. Moreover, a protein-protein interaction network was constructed using the identified DEGs, and hub gene analysis was performed. Furthermore, correlation analyses between key genes and pathological characteristics of DKD indicated that CCR4, NTNG1, HGF and ISL1 are related to DKD, and NTNG1 and HGF may server as diagnostic biomarkers in DKD using the receiver-operator characteristic (ROC) curve. Collectively, our findings established 2 reliable biomarkers for DKD.


Assuntos
Nefropatias Diabéticas/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Rim/metabolismo , Netrinas/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Proteínas Ligadas por GPI/metabolismo , Humanos
2.
Chemosphere ; 238: 124595, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31445330

RESUMO

Earthworms are often used as test subjects in toxicological studies, due to their ubiquitousness and sensitivity to contaminant exposure. Such testing is typically conducted using Eisenia fetida as the test subject, but continued use of E. fetida (eco) toxicology is questionable. Therefore, in this study three earthworm species, Aporrectodea rosea, Aporrectodea trapezoides and E. fetida, were exposed to lethal and sublethal concentrations of cadmium (Cd) and lead (Pb) nitrate in artificial soil for 7, 14 and 28 days. A biomarker of genotoxicity (TUNEL assay), biochemical markers [malondialdehyde (MDA) and total antioxidant capacity (TAC)], weight loss, lethal toxicity (LC50) and subcellular partitioning were assessed. Cadmium and Pb caused significant inhibition in TAC and growth and significant increases in DNA damage and lipid peroxidation in the earthworms. Acute toxicity rank (14 days) for both Cd and Pb were E. fetida > A. trapezoides > A. rosea. Subcellular partitioning of Cd and Pb in the earthworms were cytosol > debris > granules and debris > granules > cytosol, respectively. Comparison of biomarker responses between study species showed that E. fetida proved to be less susceptible to Cd and Pb exposure than A. rosea and A. trapezoides. Therefore, this study confirms that A. rosea and A. trapezoides are more suitable as subjects than E. fetida for the soil toxicity tests, because of both their greater susceptibility to toxicants and in their abundance in the field.


Assuntos
Cádmio/toxicidade , Chumbo/toxicidade , Oligoquetos/metabolismo , Poluentes do Solo/toxicidade , Animais , Biomarcadores/metabolismo , Dano ao DNA/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Oligoquetos/classificação , Solo/química , Poluentes do Solo/análise , Testes de Toxicidade
3.
Bratisl Lek Listy ; 120(12): 924-928, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31855052

RESUMO

OBJECTIVES: The aim of this study was to investigate the relationship between thromboxane levels and oxidative stress in children with Crohn´s disease (CD), and examine the effect of natural polyphenolic compounds on thromboxane levels. METHODS: This study involved 14 children suffering from CD and 15 healthy controls. Patients were receiving the polyphenolic extract Pycnogenol for 10 weeks. Plasma levels of the static and dynamic forms of thromboxane B2 as well as their metabolite 11-dehydro thromboxane B2 in urine were determined. RESULTS: In comparison to controls, CD patients had significantly higher levels of the static and dynamic forms of thromboxane B2. Pycnogenol decreased the level of the dynamic form of thromboxane B2 after 10 weeks of administration. CONCLUSIONS: Paediatric Crohn's disease is associated with higher thromboxane levels. Our results indicate that Pycnogenol administration reduces thromboxane levels, which may positively influence some clinical symptoms of CD such as thromboembolic episodes (Tab. 3, Ref. 49).


Assuntos
Doença de Crohn/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Tromboxanos/sangue , Adolescente , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Feminino , Flavonoides/administração & dosagem , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem
5.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4234-4240, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872704

RESUMO

The aim of this paper was to screen out relevant genes of geniposide-induced hepatotoxicity based on genomics,in order to provide a scientific basis for the non-clinical evaluation of drugs containing Gardeniae Fructus and geniposide. Fifty-five SD rats were randomly divided into normal control group,24 h group and 72 h group. The changes of appearance,behavior and weight of rats were observed after administration by gavage for 3 days. The activities of ALT and AST were detected. Molecular mechanism of geniposideinduced hepatotoxicity was investigated by Affymetrix miRNA 4. 0 and Affymetrix Rat Gene 2. 0 to examine the gene expression levels in Sprague-Dawley rat livers at 24 h and 72 h after administration of overdose-geniposide( 300 mg·kg-1 daily),and then verified by Realtime quantitative PCR. Compared with the normal control group,the activities of ALT and AST were markedly increased. In addition,experimental results indicated that 324 genes were differentially expressed,among which 259 were up-regulated and 65 down-regulated.Nine candidate genes were verified by qRT-PCR,including Bcl2,Il1 b,Tpm3,MMP2,Col1α1,Ifit1,Aldob,Nr0 b2,Cyp2 c23. And Bcl2,Col1α1,Aldob,Nr0 b2 and Cyp2 c23 were found to be correlated with geniposide-induced hepatotoxicity. This study provides an important clue for mechanism of geniposide-induced hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Iridoides/toxicidade , Animais , Biomarcadores/metabolismo , Genômica , Fígado/metabolismo , Ratos , Ratos Sprague-Dawley
6.
J Environ Pathol Toxicol Oncol ; 38(3): 229-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679310

RESUMO

Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.


Assuntos
Antiasmáticos/farmacologia , Antioxidantes/metabolismo , Asma/tratamento farmacológico , Citocinas/imunologia , Inflamação/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/farmacologia , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/química , Citocinas/efeitos dos fármacos , Inflamação/induzido quimicamente , Masculino , Camundongos , Ovalbumina/toxicidade
7.
Plant Mol Biol ; 101(4-5): 343-354, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31621005

RESUMO

KEY MESSAGE: Short review focussing on the role and targeting of vacuolar substructure in plant immunity and pathogenesis. Plants lack specialized immune cells, therefore each plant cell must defend itself against invading pathogens. A typical plant defense strategy is the hypersensitive response that results in host cell death at the site of infection, a process largely regulated by the vacuole. In plant cells, the vacuole is a vital organelle that plays a central role in numerous fundamental processes, such as development, reproduction, and cellular responses to biotic and abiotic stimuli. It shows divergent membranous structures that are continuously transforming. Recent technical advances in visualization and live-cell imaging have significantly altered our view of the vacuolar structures and their dynamics. Understanding the active nature of the vacuolar structures and the mechanisms of vacuole-mediated defense responses is of great importance in understanding plant-pathogen interactions. In this review, we present an overview of the current knowledge about the vacuole and its internal structures, as well as their role in plant-microbe interactions. There is so far limited information on the modulation of the vacuolar structures by pathogens, but recent research has identified the vacuole as a possible target of microbial interference.


Assuntos
Interações Hospedeiro-Patógeno , Imunidade Vegetal , Plantas/ultraestrutura , Vacúolos/ultraestrutura , Biomarcadores/metabolismo , Morte Celular , Membranas Intracelulares/imunologia , Membranas Intracelulares/microbiologia , Membranas Intracelulares/ultraestrutura , Proteínas de Plantas/metabolismo , Plantas/imunologia , Plantas/microbiologia , Vacúolos/imunologia , Vacúolos/microbiologia
8.
Clin Exp Rheumatol ; 37 Suppl 120(5): 73-87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621570

RESUMO

Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing the projects with the highest chance of success. Biomarkers for enrichment of clinical studies, early efficacy as well as other diagnostic tools are needed. Osteoporosis and OA have many similarities. In osteoporosis an armamentarium of treatments are now available with high clinical efficacy and well-described effects on biomarkers. Possibly, lessons learned from the osteoporosis field in the use of biomarkers may be applied in the OA field, from both technical and scientific perspectives. To help guide the way, the FDA has recently published the BEST guidelines, to facilitate obtaining a common vocabulary to assist biomarker researchers. In the current review, we will review the biomarkers of OA, with emphasis on bone, cartilage and synovial biomarkers, and draw clear perspectives to the use of biomarkers for drug development and clinical practice in the osteoporosis field.


Assuntos
Biomarcadores/análise , Cartilagem Articular , Osteoartrite , Biomarcadores/metabolismo , Cartilagem Articular/metabolismo , Humanos , Osteoartrite/metabolismo , Osteoporose/metabolismo , Membrana Sinovial
9.
Results Probl Cell Differ ; 68: 321-353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598863

RESUMO

When shifting research focus from model to non-model species, many differences in the working approach should be taken into account and usually methodological modifications are required because of the lack of genetics/genomics and developmental information for the vast majority of organisms. This lack of data accounts for the largely incomplete understanding of how the two components-genes and developmental programs-are intermingled in the process of evolution. A deeper level of knowledge was reached for a few model animals, making it possible to understand some of the processes that guide developmental changes during evolutionary time. However, it is often difficult to transfer the obtained information to other, even closely related, animals. In this chapter, we present and discuss some examples, such as the choice of molecular markers to be used to characterize differentiation and developmental processes. The chosen examples pertain to the study of germline in molluscs, reptiles, and other non-model animals.


Assuntos
Biomarcadores/metabolismo , Diferenciação Celular , Células Germinativas/citologia , Células Germinativas/metabolismo , Moluscos/citologia , Répteis , Animais , Biomarcadores/análise , Répteis/embriologia
10.
Results Probl Cell Differ ; 68: 355-377, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598864

RESUMO

The knowledge of the morphological and functional aspects of mammalian glial cells has greatly increased in the last few decades. Glial cells represent the most diffused cell type in the central nervous system, and they play a critical role in the development and function of the brain. Glial cell dysfunction has recently been shown to contribute to various neurological disorders, such as autism, schizophrenia, pain, and neurodegeneration. For this reason, glia constitutes an interesting area of research because of its clinical, diagnostic, and pharmacological relapses. In this chapter, we present and discuss the cytoarchitecture of glial cells in tetrapods from an evolutive perspective. GFAP and vimentin are main components of the intermediate filaments of glial cells and are used as cytoskeletal molecular markers because of their high degree of conservation in the various vertebrate groups. In the anamniotic tetrapods and their progenitors, Rhipidistia (Dipnoi are the only extant rhipidistian fish), the cytoskeletal markers show a model based exclusively on radial glial cells. In the transition from primitive vertebrates to successively evolved forms, the emergence of a new model has been observed which is believed to support the most complex functional aspects of the nervous system in the vertebrates. In reptiles, radial glial cells are prevalent, but star-shaped astrocytes begin to appear in the midbrain. In endothermic amniotes (birds and mammals), star-shaped astrocytes are predominant. In glial cells, vimentin is indicative of immature cells, while GFAP indicates mature ones.Olfactory receptor neurons undergo continuous turnover, so they are an easy model for neurogenesis studies. Moreover, they are useful in neurotoxicity studies because of the exposed position of their apical pole to the external environment. Among vertebrates, fish represent a valid biological model in this field. In particular, zebrafish, already used in laboratories for embryological, neurobiological, genetic, and pathophysiological studies, is the reference organism in olfactory system research. Smell plays an important role in the reproductive behavior of fish, with direct influences also on the numerical consistency of their populations. Taking into account that a lot of species have considerable economic importance, it is necessary to verify if the model of zebrafish olfactory organ is also directly applicable to other fish. In this chapter, we focus on crypt cells, a morphological type of olfactory cells specific of fish. We describe hypothetical function (probably related with social behavior) and evolutive position of these cells (prior to the appearance of the vomeronasal organ in tetrapods). We also offer the first comparison of the molecular characteristics of these receptors between zebrafish and the guppy. Interestingly, the immunohistochemical expression patterns of known crypt cell markers are not overlapping in the two species.


Assuntos
Biomarcadores/metabolismo , Neuroglia/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Peixe-Zebra , Animais , Neurogênese , Peixe-Zebra/fisiologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-31594645

RESUMO

The number of disorders now linked to increased intestinal mucosal permeability implies that a substantial percent of the population is affected. Drug interventions targeting reduced tight junctional permeability are being pursued. Although hyper-permeability in itself is not a clinically recognized disease entity, its relationship to disease processes has driven interest in measuring, and even monitoring mucosal permeability in vivo. Along with improved knowledge of gut barrier physiology, advances have been made in tests and biomarkers of barrier function. Drawing from our experiences in the past decade, considerations and challenges faced in assessing in vivo intestinal permeability are discussed herein, along with indications of what the future might hold.


Assuntos
Biomarcadores/metabolismo , Mucosa Intestinal/fisiologia , Intestinos/fisiopatologia , Permeabilidade , Humanos
12.
J Assoc Physicians India ; 67(10): 54-56, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31571453

RESUMO

Background: Attention has increasingly turned towards the role of factors, such as inflammation in the development of atherosclerosis and CHD. C-reactive protein (CRP) has emerged as one of the most important novel inflammatory marker. Subsequent risk modification and treatment strategies of CHD keeping on pointer towards inflammation may be the appropriate approach. Aim: The aim of this study was to determine the association of CHD with CRP, a sensitive marker of inflammation. Material and Methods: This is a case control study amongst 300 subjects (150 cases and 150 controls), conducted in the Department of Cardiology at Sri Aurobindo Medical College and P.G Institute, Indore, M.P. Subjects with definite diagnosis of CHD established by coronary angiography (CAG) was taken as cases, subjects matched with age, gender with no conventional risk factor and past history of CHD from the relatives and accompanying persons were enlisted as controls. Results: Estimation of CRP reveals ≥0.6 mg/dl in 88(58.7%) subjects out of 150, compared to 26 (17.3%) control subjects out of 150 which is statistically significant (p value<0.0001) (OR=6.7). Conclusion: CRP as a noble marker of inflammation was significantly higher in subjects of CHD and thus supported adequately the hypothesis of an activation of inflammatory cascade for coronary atheromatous plaque formation and causation of CHD.


Assuntos
Proteína C-Reativa/metabolismo , Doença das Coronárias/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Humanos , Inflamação/metabolismo , Fatores de Risco
13.
J Clin Pathol ; 72(12): 785-799, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31611285

RESUMO

Progresses in liquid-based assays may provide novel useful non-invasive indicators of cardiovascular (CV) diseases. By analysing circulating cells or their products in blood, saliva and urine samples, we can investigate molecular changes present at specific time points in each patient allowing sequential monitoring of disease evolution. For example, an increased number of circulating endothelial cells may be a diagnostic biomarker for diabetic nephropathy and heart failure with preserved ejection fraction. The assessment of circulating cell-free DNA (cfDNA) levels may be useful to predict severity of acute myocardial infarction, as well as diagnose heart graft rejection. Remarkably, circulating epigenetic biomarkers, including DNA methylation, histone modifications and non-coding RNAs are key pathogenic determinants of CV diseases representing putative useful biomarkers and drug targets. For example, the unmethylated FAM101A gene may specifically trace cfDNA derived from cardiomyocyte death providing a powerful diagnostic biomarker of apoptosis during ischaemia. Moreover, changes in plasma levels of circulating miR-92 may predict acute coronary syndrome onset in patients with diabetes. Now, network medicine provides a framework to analyse a huge amount of big data by describing a CV disease as a result of a chain of molecular perturbations rather than a single defect (reductionism). We outline advantages and challenges of liquid biopsy with respect to traditional tissue biopsy and summarise the main completed and ongoing clinical trials in CV diseases. Furthermore, we discuss the importance of combining fluid-based assays, big data and network medicine to improve precision medicine and personalised therapy in this field.


Assuntos
Líquidos Corporais/metabolismo , Doenças Cardiovasculares/diagnóstico , Técnicas de Diagnóstico Molecular , Medicina de Precisão , Biomarcadores/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Ácidos Nucleicos Livres/sangue , Tomada de Decisão Clínica , Humanos , Biópsia Líquida , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes
14.
Expert Opin Investig Drugs ; 28(11): 951-965, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31614096

RESUMO

Introduction: Dementia with Lewy bodies (DLB) is an under-researched area despite being the second most common type of degenerative dementia after Alzheimer's disease. It is an area of unmet need with no approved symptomatic or disease-modifying therapies. The pharmacological management of DLB is complex and challenging because early trials of drugs for DLB have resulted in no demonstrable efficacy. Randomized controlled trials (RCTs) in the DLB population have only recently been initiated. Understanding results from previous and current clinical trials in DLB can provide insights for future research and development.Areas covered: We provide an overview of the DLB drug development landscape and the current treatment strategies. We reviewed ClinicalTrials.gov to identify all clinical trials for the treatment of DLB.Expert opinion: DLB drug development has significantly improved in recent years with eight agents now in clinical trials. However, more rigorous RCTs are urgently needed. Diagnostic criteria must be optimized to accurately diagnose patients for clinical trials and care. New biomarker strategies are necessary to improve diagnostic capabilities and trial designs, and novel drug targets should be identified to develop DLB specific disease-modifying therapies. Evaluating the current drug development landscape can provide insight into how best to optimize development practices.


Assuntos
Desenvolvimento de Medicamentos , Doença por Corpos de Lewy/tratamento farmacológico , Terapia de Alvo Molecular , Animais , Biomarcadores/metabolismo , Humanos , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Prague Med Rep ; 120(2-3): 103-106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31586509

RESUMO

Myristic acid was identified as a metabolite with the highest diagnostic sensitivity and specificity in the metabolome of patients with bacteraemia. Subsequently, its significant decrease was observed in patients in septic shock not responding to treatment. In our study we have captured myristic acid serum level kinetics in 96 hours following accidental intravenous self-administration of eubiotic Hylak forte causing infection-like systemic inflammatory response syndrome (SIRS). To our knowledge, this is the first time the kinetics of myristic acid levels is presented in a septic patient. Myristic acid was evaluated in comparison with other inflammatory biomarkers and with its level in a control group of healthy subjects. Myristic acid levels during septic response were significantly elevated in comparison with the control group. The peak level was recorded almost immediately after the insult with a gradual decrease within 96 hours. Myristic acid appears to be a promising biomarker in sepsis diagnostics, further research by our group into this topic is ongoing.


Assuntos
Ácido Mirístico/metabolismo , Sepse/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Humanos , Inflamação/metabolismo , Cinética , Choque Séptico/metabolismo , Síndrome
16.
Adv Exp Med Biol ; 1164: 47-61, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576539

RESUMO

Stem cell antigen-1 (Sca-1) is the first identified member of mouse Ly6 gene family. We discovered that Sca-1 disrupts TGFß signaling and enhances mammary tumorigenesis in a DMBA-induced mammary tumor model. Sca-1 gene is lost during evolution in humans. Human Ly6 genes Ly6D, LyE, LyH, and LyK on human chromosome 8q24.3 genes are syntenic to the mouse chromosome 15 where Sca-1 is located. We found that Ly6D, E, H, and K are upregulated in human cancer compared to normal tissue and that the increased expression of these genes are associated with poor prognosis of multiple types of human cancer. Several other groups have indicated increased expression of Ly6 genes in human cancer. Here we described the relevance of expression of human Ly6D, LyE, LyH, and LyK in functioning of normal tissues and tumor progression.


Assuntos
Antígenos Ly , Biomarcadores , Regulação Neoplásica da Expressão Gênica , Neoplasias , Animais , Antígenos Ly/genética , Biomarcadores/metabolismo , Transformação Celular Neoplásica , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Prognóstico
17.
Medicine (Baltimore) ; 98(40): e17471, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577778

RESUMO

Hand, foot, and mouth disease (HFMD) spreads rapidly and has been recognized as a public health problem in recent years in China. Unfortunately, there is no effective vaccine or antiviral drug currently for EV71 infection. In this study, we aim to identify biomarker which are associated with for severity of EV71 infection cases using high-throughput RNA sequencing approach.RNA sequencing of samples from severe HFMD (S) patients group (n = 10) and control HFMD (C) patients group (n = 10) were performed and the results were verified by qPCR. mRNA with the highest expression level was selected to be validated in an independent cohort comprising of 45 severe EV71 infected patients and 45 control by qPCR assay.Seventeen significant differentially expressed genes were identified. Scavenger receptor class A, member 3 (SCARA3) was one of the significantly upregulated genes with the highest expression level and was selected for validation. The mean relative expression levels in severe HFMD and control HFMD patients were 10.1-fold and 5.0-fold, respectively, P value <.001.We found that SCARA3 is associated with severity of HFMD, and it may be a potential prognostic marker to predict the HFMD progression in EV71 infected patients.


Assuntos
Doença de Mão, Pé e Boca/diagnóstico , Doença de Mão, Pé e Boca/genética , Proteínas de Choque Térmico/genética , Receptores Depuradores Classe A/genética , Biomarcadores/metabolismo , Estudos de Casos e Controles , Pré-Escolar , Feminino , Doença de Mão, Pé e Boca/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Lactente , Masculino , RNA Mensageiro/metabolismo , Receptores Depuradores Classe A/metabolismo , Índice de Gravidade de Doença
18.
Zhonghua Yan Ke Za Zhi ; 55(10): 769-776, 2019 Oct 11.
Artigo em Chinês | MEDLINE | ID: mdl-31607066

RESUMO

Objective: To identify differentially expressed proteins between the patients with proliferative diabetic retinopathy (PDR) and vitreous floaters, and explore treatment target for PDR based on isobaric tags for relative and absolute quantification (iTRAQ) LC-MS/MS Proteomics. Method: Vitreous samples were collected from 28 eyes of patients with PDR and 4 eyes with vitreous floaters, which served as controls. For quantitative proteomics, vitreous samples were combined and proteins extracted and labeled with iTRAQ peptide-tagging reagents. Samples were fractionated by liquid chromatography (LC), analyzed by tandem mass spectrometry (MS/MS) and Gene Ontology (GO) analyses performed on differentially expressed proteins identified in the PDR samples. Results: In the PDR vitreous, 26 proteins were identified that were differentially expressed when compared to the controls. Of these, 7 showed a significant increase (P<0.05) and 19 a significant decrease (P<0.05)in expression in PDR patients. These included some high abundance proteins including Retinoic acid receptor reactive protein 2 (PDR 1=85.0, PDR 2=83.0, Control 1=119.6, Control 2=120.2, FC=0.710, P=0.001), Semaphorin-4B(PDR 1=64.4, PDR 2=68.8, Control 1=135.4, Control 2=146.0, FC=0.473, P=0.023), Apolipoprotein B (PDR 1=104.4, PDR 2=106.6, Control 1=89.0, Control 2=85.3, FC=1.211, P=0.024), and Heat shock protein 70 (PDR 1=69.3, PDR 2=75.0, Control 1=137.7, Control 2=138.3, FC=0.523, P=0.026), which are closely related to the pathological mechanism of PDR. GO analysis clustered the differentially expressed genes into three major functional domains: Biological Processes, Molecular Function and Cellular Component. Differential gene expression was found in the categories of cellular metabolism, organonitrogen compound and carbohydrate derivative metabolic processes, transferase activity and transmembrane signaling receptor activity. KEGG Pathway analysis indicate that Chemerin signaling through Akt, Sema4B signaling via PI3K, and HIF-1α signal pathways were all altered in the PDR samples. Conclusions: In this study we identified variations in expression of genes extensively involved in key biological processes in the retina including neovascularization, cellular metabolism and transmembrane signaling, which provide new insights into the pathophysiology of PDR. Extracellular matrix was degraded and endothelial cell migration was induced by Chemerin, in addition, the destruction of blood-retinal barrier and neuronal apoptosis were induced by ApoB. Chemerin and ApoB accelerated the development of PDR. Sema 4B participated in vascular protection, HSP70 conducted anti-apoptosis. These two cytokines protected the retinal neurovascular in PDR patients. Therefore, Chemerin, Sema 4B, ApoB and HSP70 may be the treatment target for PDR. (Chin J Ophthalmol, 2019, 55:769-776).


Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Corpo Vítreo/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Quimiocinas/metabolismo , Cromatografia Líquida/métodos , Diabetes Mellitus Tipo 2/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Proteoma/análise , Espectrometria de Massas em Tandem/métodos , Corpo Vítreo/química
19.
J Agric Food Chem ; 67(44): 12191-12198, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31588747

RESUMO

Fermented black garlic has multiple beneficial biological activities, including cardiovascular protection, anticancer, hepatoprotective, and antibacterial properties. In this study, metabolic differences in the properties of black and fresh garlic were investigated via liquid chromatography quadrupole/time-of-flight-based metabolomics, leading to the identification of characteristic components. Fermented black garlic samples and their Amadori products (AC) promoted angiogenesis, prevented thrombus formation by rescuing chemical-induced vascular lesions in zebrafish, and inhibited H2O2-induced injury of endothelial cells, thus reducing the risk of cardiovascular disease. AC suppressed activation of the mitogen-activated protein kinase pathway through inhibition of p38 and ERK1/2 phosphorylation, in turn, increasing the availability of c-Fos/c-Jun or c-Jun/c-Jun complexes for apoptotic resistance. Clarification of the associated signaling pathways should therefore provide a solid foundation for optimization of black garlic-based therapies.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Alho/química , Extratos Vegetais/administração & dosagem , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Humanos , Peróxido de Hidrogênio/toxicidade , Masculino , Espectrometria de Massas , Metabolômica , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
20.
Zhonghua Zhong Liu Za Zhi ; 41(10): 753-759, 2019 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-31648497

RESUMO

Objective: To investigate the effects of miR-23a-3p on proliferation, migration and apoptosis on human acute myeloid leukemia (AML) cells by targeting SMC1A. Methods: Microarray analysis was used to screen differentially expressed microRNAs and mRNAs in human AML cells. Real-time fluorescence quantitative PCR (RT-qRCR) was used to detect the expressions of miR-23a-3p and SMCA in human AML cell line U937. TargetScan database was used to analyze the correlation between miR-23a-3p and SMC1A. Double luciferase reporter gene was used to detect the interaction between miR-23a-3p and SMC1A. The effect of miR-23a-3p expression on the proliferation of U937 cells was detected by clonal assay. The migration, apoptosis, cell cycle and caspase-3 activity of U937 cells regulated by miR-23a-3p were detected by cell scratch assay and flow cytometry, respectively. Western blot was used to detect the expressions of Bax and Bcl-2 in U937 cells. Results: Compared with human normal monocyte SC group (1.00), the expression of miR-23a-3p in U937 cells was up-regulated (2.56±0.78) (P<0.01), while the expression of SMC1A was down-regulated (0.48±0.56, P<0.01). miR-23a-3p specifically bond to SMC1A 3'UTR and regulated the expression activity of SMC1A. Overexpression of miR-23a-3p promoted the proliferation and migration of U937 cells and inhibited the apoptosis of U937 cells, while up-regulation of SMC1A inhibited the proliferation and migration of U937 cells and promoted the apoptosis of U937 cells. The percentages of G(0)/G1 phase, G(2)/M phase and S phase cells in the negative control group were (37.48±0.21)%, (16.78±0.18)% and (45.74±0.15)% respectively, and those in the miR-23a-3p mimics group were (19.96±0.11)%, (41.69±0.24)% and (38.24±0.34)%, respectively. The difference was statistically significant (all P<0.05). The proportions of G(0)/G(1) phase, G(2)/M phase and S phase cells in the group of miR-23a-3p mimics+ pcDNA3.1-SMC1A were (36.88±0.21)%, (30.44±0.33)% and (32.88±0.16)%, respectively, without significant difference when compared with those of the miR-23a-3p mimics group (P>0.05). The relative expression levels of Bax and Bcl-2 protein in the negative control group were 0.55±0.45 and 0.31±0.54, respectively. Overexpression of miR-23a-3p inhibited the expression of Bax protein in U937 cells (0.23±0.13, P<0.001), promoted the expression of Bcl-2 protein (0.50±0.23, P<0.01), while SMC1A increased the expression of Bax protein in U937 cells (0.40±0.11, P<0.01), and inhibited the expression of Bcl-2 protein (0.37±0.15). In the negative control group, caspase-3 activity was (25.82±0.89)%. Overexpression of miR-23a-3p inhibited caspase-3 activity in U937 cells (3.64±0.56)%, P<0.01, while up-regulation of SMC1A promoted caspase-3 activity in U937 cells (15.29±0.85)%, P<0.01. Conclusion: miR-23a-3p can inhibit the proliferation and migration and promote apoptosis of human AML cells by targeting SMC1A.


Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , MicroRNAs/genética , Biomarcadores/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proteínas Cromossômicas não Histona , Humanos , Leucemia Mieloide Aguda/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
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