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1.
PLoS Pathog ; 17(9): e1009892, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34555119

RESUMO

In this essay, we show that 3 distinct approaches to immunological exhaustion coexist and that they only partially overlap, generating potential misunderstandings. Exploring cases ranging from viral infections to cancer, we propose that it is crucial, for experimental and therapeutic purposes, to clarify these approaches and their interconnections so as to make the concept of exhaustion genuinely operational.


Assuntos
Fenômenos do Sistema Imunológico , Linfócitos T/imunologia , Animais , Humanos
2.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299312

RESUMO

It is well known that lifestyle changes can alter several physiological functions in the human body. For exercise and diet, these effects are used sensibly in basic therapies, as in cardiovascular diseases. However, the physiological changes induced by exercise and a modified diet also have the capacity to influence the efficacy and toxicity of several drugs, mainly by affecting different pharmacokinetic mechanisms. This pharmacological plasticity is not clinically relevant in all cases but might play an important role in altering the effects of very common drugs, particularly drugs with a narrow therapeutic window. Therefore, with this review, we provide insights into possible food-drug and exercise-drug interactions to sharpen awareness of the potential occurrence of such effects.


Assuntos
Dieta , Exercício Físico/fisiologia , Farmacocinética , Peso Corporal , Dieta Saudável , Interações Medicamentosas , Interações Alimento-Droga , Humanos , Fenômenos do Sistema Imunológico , Estilo de Vida , Microbiota , Modelos Biológicos , Fenômenos Fisiológicos da Nutrição
3.
Genes (Basel) ; 12(5)2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-34069220

RESUMO

Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting α (ATP7A) gene. Our objective was to identify genomic alterations and circulating proteomic profiles related to MD assessing their potential roles in the clinical features of the disease. We describe the case of a male patient of 8 months of age with silvery hair, tan skin color, hypotonia, alterations in neurodevelopment, presence of seizures, and low values of plasma ceruloplasmin. Trio-whole-exome sequencing (Trio-WES) analysis, plasma proteome screening, and blood cell migration assays were carried out. Trio-WES revealed a hemizygous change c.4190C > T (p.S1397F) in exon 22 of the ATP7A gene. Compared with his parents and with child controls, 11 plasma proteins were upregulated and 59 downregulated in the patient. According to their biological processes, 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins (p = 9.44 × 10-11). Additional studies are necessary to validate these findings as hallmarks of MD.


Assuntos
Movimento Celular/genética , Fenômenos do Sistema Imunológico/genética , Síndrome dos Cabelos Torcidos/genética , Proteoma/genética , Adolescente , Adulto , ATPases Transportadoras de Cobre/genética , Regulação para Baixo/genética , Feminino , Humanos , Lactente , Masculino , Mutação/genética , Proteômica/métodos , Regulação para Cima/genética , Sequenciamento Completo do Exoma/métodos , Adulto Jovem
4.
Infect Dis Now ; 51(5): 418-423, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33991720

RESUMO

Since the beginning of the COVID-19 pandemic, reduced incidence of many viral and bacterial infections has been reported in children: bronchiolitis, varicella, measles, pertussis, pneumococcal and meningococcal invasive diseases. The purpose of this opinion paper is to discuss various situations that could lead to larger epidemics when the non-pharmaceutical interventions (NPI) imposed by the SARS-CoV-2 epidemic will no longer be necessary. While NPIs limited the transmission of SARS-CoV-2, they also reduced the spread of other pathogens during and after lockdown periods, despite the re-opening of schools since June 2020 in France. This positive collateral effect in the short term is welcome as it prevents additional overload of the healthcare system. The lack of immune stimulation due to the reduced circulation of microbial agents and to the related reduced vaccine uptake induced an "immunity debt" which could have negative consequences when the pandemic is under control and NPIs are lifted. The longer these periods of "viral or bacterial low-exposure" are, the greater the likelihood of future epidemics. This is due to a growing proportion of "susceptible" people and a declined herd immunity in the population. The observed delay in vaccination program without effective catch-up and the decrease in viral and bacterial exposures lead to a rebound risk of vaccine-preventable diseases. With a vaccination schedule that does not include vaccines against rotavirus, varicella, and serogroup B and ACYW Neisseria meningitidis, France could become more vulnerable to some of these rebound effects.


Assuntos
COVID-19/imunologia , Fenômenos do Sistema Imunológico , Infecções/epidemiologia , Vacinas/imunologia , Criança , Humanos
5.
Nutrients ; 13(4)2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33919499

RESUMO

Autism spectrum disorder (ASD) pathophysiology is not completely understood; however, altered inflammatory response and glutamate signaling have been reported, leading to the investigation of molecules targeting the immune-glutamatergic system in ASD treatment. Palmitoylethanolamide (PEA) is a naturally occurring saturated N-acylethanolamine that has proven to be effective in controlling inflammation, depression, epilepsy, and pain, possibly through a neuroprotective role against glutamate toxicity. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in ASD. Studies indicate altered serum/brain levels of PEA and other endocannabinoids (ECBs)/acylethanolamines (AEs) in ASD. Altered PEA signaling response to social exposure and altered expression/activity of enzymes responsible for the synthesis and catalysis of ECBs/AEs, as well as downregulation of the peroxisome proliferator activated receptor-α (PPAR-α) and cannabinoid receptor target GPR55 mRNA brain expression, have been reported. Stress and exposure to exogenous cannabinoids may modulate ECBs/AEs levels and expression of candidate genes for neuropsychiatric disorders, with implications for ASD. Limited research suggests that PEA supplementation reduces overall autism severity by improving language and social and nonsocial behaviors. Potential neurobiological underpinnings include modulation of immune response, neuroinflammation, neurotrophy, apoptosis, neurogenesis, neuroplasticity, neurodegeneration, mitochondrial function, and microbiota activity, possibly through peroxisome proliferator-activated receptor-α (PPAR-α) activation.


Assuntos
Amidas/farmacologia , Transtorno do Espectro Autista/metabolismo , Encéfalo/metabolismo , Etanolaminas/farmacologia , Fármacos Neuroprotetores/farmacologia , Ácidos Palmíticos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Endocanabinoides/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Fenômenos do Sistema Imunológico/efeitos dos fármacos , Inflamação , Mitocôndrias/efeitos dos fármacos , PPAR alfa/metabolismo , Receptores de Canabinoides/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
Multimedia | Recursos Multimídia | ID: multimedia-8267

RESUMO

¿Cómo actúan las vacunas para protegernos? Y ¿cuáles son los diferentes enfoques de los que estamos oyendo hablar con respecto a las vacunas?


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Pandemias/prevenção & controle , Vacinas Virais/imunologia , Fenômenos do Sistema Imunológico
9.
Theranostics ; 11(10): 5028-5044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754042

RESUMO

Background: Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Although several transcriptome studies have been done on placentae from PE patients, only a small number of differentially expressed genes have been identified due to very small sample sizes and no distinguishing of clinical subtypes. Methods: We carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for dysregulated genes and the molecular network and pathways they are involved in. Results: We identified two functionally distinct sets of dysregulated genes in the two major subtypes: 2,977 differentially expressed genes in early-onset severe preeclampsia, which are enriched with metabolism-related pathways, notably transporter functions; and 375 differentially expressed genes in late-onset severe preeclampsia, which are enriched with immune-related pathways. We also identified some key transcription factors, which may drive the widespread gene dysregulation in both early-onset and late-onset patients. Conclusion: These results suggest that early-onset and late-onset severe preeclampsia have different molecular mechanisms, whereas the late-onset mild preeclampsia may have no placenta-specific causal factors. A few regulators may be the key drivers of the dysregulated molecular pathways.


Assuntos
Expressão Gênica , Idade Gestacional , Placenta/metabolismo , Pré-Eclâmpsia/genética , Adulto , Metabolismo dos Carboidratos/genética , Proteínas de Transporte/genética , Feminino , Humanos , Fenômenos do Sistema Imunológico/genética , Gravidez , RNA-Seq , Índice de Gravidade de Doença , Transcriptoma
10.
Multimedia | Recursos Multimídia | ID: multimedia-8116

RESUMO

Science in 5 series - episode 18 /How long does your immunity last after you recover from COVID-19? Can you get reinfected? Why do you need to continue with preventative measures? Dr Maria Van Kerkhove explains on "Science in 5".


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Pandemias/prevenção & controle , Fenômenos do Sistema Imunológico , Máscaras , Isolamento Social ,
11.
Bioengineered ; 12(1): 540-554, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33535891

RESUMO

Preeclampsia (PE) is an important topic in obstetrics. In this study, we used weighted gene co-expression network analysis (WGCNA) to screen the key modules related to immune cell infiltration and to identify the hub genes for the molecular subtyping of PE. We first downloaded a set of PE transcriptional data (GSE75010; 157 samples: 80 PE and 77 non-PE) from the GEO database. We then analyzed the PE samples and non-PE samples for immune cell infiltration and screened cells with differences in such infiltration. Next, we downloaded the immune-related genes from an immune-related database to screen the expression profile of the immune-related genes. Then, we obtained a candidate gene set by screening the immune-related genes differentially expressed between the two groups. We used WGCNA to construct a weighted co-expression network for these candidate genes, mined co-expression modules, and then calculated the correlation between each module and immune cells with differential infiltration. We screened the modules related to infiltrating immune cells, identified the key modules' hub genes, and determined the key module genes that interacted with each other. Finally, we obtained the hub genes related to the infiltrating immune cells. We classified the preeclampsia patients by unsupervised cluster molecular typing, determined the difference of immune cell infiltration among the different PE subtypes, and calculated the expression of hub genes in these different subtypes. In conclusion, we found 41 hub genes that may be closely related to the molecular typing of PE.


Assuntos
Redes Reguladoras de Genes , Pré-Eclâmpsia , Transcriptoma , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/imunologia , Marcadores Genéticos/genética , Marcadores Genéticos/imunologia , Humanos , Fenômenos do Sistema Imunológico/genética , Leucócitos/imunologia , Macrófagos/imunologia , Tipagem Molecular , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/imunologia , Gravidez , Transcriptoma/genética , Transcriptoma/imunologia
12.
Ann Rheum Dis ; 80(5): 626-631, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33408077

RESUMO

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common type of arthritis among children, but a few studies have investigated the contribution of rare variants to JIA. In this study, we aimed to identify rare coding variants associated with JIA for the genome-wide landscape. METHODS: We established a rare variant calling and filtering pipeline and performed rare coding variant and gene-based association analyses on three RNA-seq datasets composed of 228 JIA patients in the Gene Expression Omnibus against different sets of controls, and further conducted replication in our whole-exome sequencing (WES) data of 56 JIA patients. Then we conducted differential gene expression analysis and assessed the impact of recurrent functional coding variants on gene expression and signalling pathway. RESULTS: By the RNA-seq data, we identified variants in two genes reported in literature as JIA causal variants, as well as additional 63 recurrent rare coding variants seen only in JIA patients. Among the 44 recurrent rare variants found in polyarticular patients, 10 were replicated by our WES of patients with the same JIA subtype. Several genes with recurrent functional rare coding variants have also common variants associated with autoimmune diseases. We observed immune pathways enriched for the genes with rare coding variants and differentially expressed genes. CONCLUSION: This study elucidated a novel landscape of recurrent rare coding variants in JIA patients and uncovered significant associations with JIA at the gene pathway level. The convergence of common variants and rare variants for autoimmune diseases is also highlighted in this study.


Assuntos
Artrite Juvenil/genética , Variação Genética/genética , Fenômenos do Sistema Imunológico/genética , Criança , Bases de Dados Genéticas , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Masculino , RNA-Seq , Transdução de Sinais/genética , Sequenciamento Completo do Exoma
14.
J Gen Virol ; 102(3)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33284098

RESUMO

Rabies is a lethal disease caused by Rabies lyssavirus, commonly known as rabies virus (RABV), and results in nearly 100 % death once clinical symptoms occur in human and animals. Long non-coding RNAs (lncRNAs) have been reported to be associated with viral infection. But the role of lncRNAs involved in RABV infection is still elusive. In this study, we performed global transcriptome analysis of both of lncRNA and mRNA expression profiles in wild-type (WT) and lab-attenuated RABV-infected mouse brains by using next-generation sequencing. The differentially expressed lncRNAs and mRNAs were analysed by using the edgeR package. We identified 1422 differentially expressed lncRNAs and 4475 differentially expressed mRNAs by comparing WT and lab-attenuated RABV-infected brains. Then we predicted the enriched biological pathways by the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) database based on the differentially expressed lncRNAs and mRNAs. Our analysis revealed the relationships between lncRNAs and RABV-infection-associated immune response and ion transport-related pathways, which provide a fresh insight into the potential role of lncRNA in immune evasion and neuron injury induced by WT RABV.


Assuntos
Encéfalo/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Vírus da Raiva/patogenicidade , Raiva/genética , Raiva/virologia , Animais , Transporte Biológico/genética , Encéfalo/virologia , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Fenômenos do Sistema Imunológico/genética , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Transmissão Sináptica/genética , Transcriptoma , Regulação para Cima , Carga Viral
15.
Dig Dis Sci ; 66(3): 674-693, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33289902

RESUMO

Bile acids are a group of chemically different steroids generated at the host/microbial interface. Indeed, while primary bile acids are the end-product of cholesterol breakdown in the host liver, secondary bile acids are the products of microbial metabolism. Primary and secondary bile acids along with their oxo derivatives have been identified as signaling molecules acting on a family of cell membrane and nuclear receptors collectively known as "bile acid-activated receptors." Members of this group of receptors are highly expressed throughout the gastrointestinal tract and mediate the bilateral communications of the intestinal microbiota with the host immune system. The expression and function of bile acid-activated receptors FXR, GPBAR1, PXR, VDR, and RORγt are highly dependent on the structure of the intestinal microbiota and negatively regulated by intestinal inflammation. Studies from gene ablated mice have demonstrated that FXR and GPBAR1 are essential to maintain a tolerogenic phenotype in the intestine, and their ablation promotes the polarization of intestinal T cells and macrophages toward a pro-inflammatory phenotype. RORγt inhibition by oxo-bile acids is essential to constrain Th17 polarization of intestinal lymphocytes. Gene-wide association studies and functional characterizations suggest a potential role for impaired bile acid signaling in development inflammatory bowel diseases (IBD). In this review, we will focus on how bile acids and their receptors mediate communications of intestinal microbiota with the intestinal immune system, describing dynamic changes of bile acid metabolism in IBD and the potential therapeutic application of targeting bile acid signaling in these disorders.


Assuntos
Ácidos e Sais Biliares/metabolismo , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Transdução de Sinais/imunologia , Ácidos e Sais Biliares/imunologia , Microbioma Gastrointestinal/imunologia , Humanos , Fenômenos do Sistema Imunológico/fisiologia , Mucosa Intestinal/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Acoplados a Proteínas G/metabolismo
16.
Environ Res ; 194: 110659, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33359674

RESUMO

Exposure to air pollutants may be associated with preterm birth (PB) through oxidative stress, metabolic detoxification, and immune system processes. However, no study has investigated the interactive effects of maternal air pollution and genetic polymorphisms in these pathways on risk of PB. The study included 126 PB and 310 term births. A total of 177 single nucleotide polymorphisms (SNPs) in oxidative stress, immune function, and metabolic detoxification-related genes were examined and analyzed. The China air quality index (AQI) was used as an overall estimation of ambient air pollutants. Among 177 SNPs, four SNPs (GPX4-rs376102, GLRX-rs889224, VEGFA-rs3025039, and IL1A-rs3783550) were found to have significant interactions with AQI on the risk of PB (Pinteraction were 0.001, 0.003, 0.03, and 0.04, respectively). After being stratified by the maternal genotypes in these four SNPs, 1.38 to 1.76 times of the risk of PB were observed as per interquartile range increase in maternal AQI among women who carried the GPX4-rs376102 AC/CC genotypes, the GLRX-rs889224 TT genotype, the VEGFA-rs3025039 CC genotype, or the IL1A-rs3783550 GT/TT genotypes. After adjustment for multiple comparisons, only GPX4-rs376102 and AQI interaction remained statistically significant (false discovery rate (FDR)=0.17). After additional stratification by preeclampsia (PE) status, a strongest association was observed in women who carried the GPX4-rs376102 AC/CC genotypes (OR, 2.26; 95% CI, 1.41-3.65, Pinteraction=0.0002, FDR=0.035) in the PE group. Our study provided the first evidence that association between maternal air pollution and PB risk may be modified by the genetic polymorphisms in oxidative stress and immune function genes. Future large studies are necessary to replicate and confirm the observed associations.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Fenômenos do Sistema Imunológico , Nascimento Prematuro , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , China/epidemiologia , Feminino , Humanos , Imunidade , Recém-Nascido , Exposição Materna/efeitos adversos , Estresse Oxidativo/genética , Material Particulado/análise , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/genética
17.
Methods Mol Biol ; 2201: 199-207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32975801

RESUMO

The discovery of opioid receptor expression on immune cells has originated a large research activity on the possible modulation by opioid drugs of immune system responses. In this chapter we describe an easy methodology useful to obtain information about the potential immunomodulatory activity of opioid drugs. An in vivo treatment schedule is used, and macrophages are studied for their ability to release different cytokines.


Assuntos
Citocinas/análise , Macrófagos/efeitos dos fármacos , Cultura Primária de Células/métodos , Analgésicos Opioides/imunologia , Analgésicos Opioides/farmacologia , Animais , Citocinas/efeitos dos fármacos , Fenômenos do Sistema Imunológico , Fatores Imunológicos/análise , Fatores Imunológicos/farmacologia , Imunomodulação/efeitos dos fármacos , Imunomodulação/imunologia , Macrófagos/metabolismo , Camundongos , Morfina/efeitos adversos , Morfina/metabolismo , Morfina/farmacologia , Receptores Opioides/imunologia
18.
Methods Mol Biol ; 2201: 209-217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32975802

RESUMO

The immune system is a complex and finely orchestrated system, and many soluble molecules and receptors contribute to its regulation.Recent studies have suggested that many of the modulatory effects induced by morphine on innate immunity, and in particular the effects on macrophage activation and function, can be due to the modulation of an important macrophage surface receptor, the toll-like receptor (TLR), that is primarily involved in early regulatory steps. In this chapter we describe a RT-real-time PCR method for assessing TLR expression in macrophage after in vivo morphine treatment.


Assuntos
Macrófagos/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptor 4 Toll-Like/análise , Analgésicos Opioides/imunologia , Analgésicos Opioides/farmacologia , Animais , Citocinas/biossíntese , Fenômenos do Sistema Imunológico , Imunidade Inata/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Morfina/efeitos adversos , Morfina/metabolismo , Morfina/farmacologia , Receptores Opioides/imunologia , Receptor 4 Toll-Like/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
19.
Multimedia | Recursos Multimídia | ID: multimedia-7895

RESUMO

How do vaccines work to protect us? What are the vaccine technologies in the pipeline and how do we ensure safe vaccines? Dr Katherine O’ Brien explains in Science in 5 !


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pneumonia Viral/prevenção & controle , Pandemias/prevenção & controle , Vacinas Virais/imunologia , Fenômenos do Sistema Imunológico
20.
Medicine (Baltimore) ; 99(49): e23554, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285774

RESUMO

Targeting protein for Xenopus kinesin-like protein 2 (TPX2) has been identified as an oncogene in multiple cancers. However, the associations among TPX2 expression, prognosis, and tumor immunity in hepatic cell cancer (HCC) have not been explored. We analyzed TPX2 expression by multiple gene expression databases, including Oncomine, TIMER, and UALCAN. The prognosis effect of TPX2 was analyzed by Kaplan--Meier plotter. The coexpressed genes with TPX2 were analyzed using Linked Omics. The association among TPX2 and immune infiltrates and immune checkpoints was determined by TIMER. It was found that TPX2 expression was notably upregulated in multiple HCC tissues. Overexpression of TPX2 has associations with race, age, weight, clinical stage and tumor grade, as well as poor prognosis in overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and disease-specific survival (DSS). In addition, TPX2 expression has a positive association with the infiltration of immune cells and the expression of immune checkpoint molecules. Coexpressed genes and functional network analysis suggested several potential mechanisms of TPX2 affecting HCC progression. The findings reveal that TPX2 has associations with prognosis and infiltration of immune cells in HCC patients, which has laid a basis for in-depth study of TPX2 role in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/imunologia , Fenômenos do Sistema Imunológico/genética , Neoplasias Hepáticas/genética , Proteínas Associadas aos Microtúbulos/imunologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Estimativa de Kaplan-Meier , Fígado/imunologia , Fígado/metabolismo , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Taxa de Sobrevida
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