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1.
MedComm (2020) ; 2(2): 207-220, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34766142

RESUMO

Adoptive cellular immunotherapy harnessing the intrinsic immune system for precise treatment has exhibited preliminary success against malignant tumors. As one of the emerging roles in adoptive cellular immunotherapy, neoantigen-reactive T cell (NRT) focuses on the antigens expressed only by tumor cells. It exclusively obliterates tumor and spares normal tissues, achieving more satisfying effects. However, the development of NRT immunotherapy remains in a relatively primitive stage. Current challenges include identification of NRTs and maintenance of adoptive cell efficacy in vivo. The possible side effects and other limitations of this treatment also hinder its application. Here, we present an overview of NRT immunotherapy and discuss the progress and challenges as well as the prospects in this promising field.

2.
Biomed Res Int ; 2021: 6653802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860048

RESUMO

Objective: Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. Methods: Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. Results: 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 (degree = 24), GNB3 (degree = 23), QSOX1 (degree = 21), and APOB (degree = 17). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. Conclusion: Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM.


Assuntos
Cardiomiopatia Dilatada/genética , Epigenoma , Genoma Humano , Genômica , Transcriptoma/genética , Cardiomiopatia Dilatada/sangue , Metilação de DNA/genética , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Mapas de Interação de Proteínas/genética , Reprodutibilidade dos Testes , Sequenciamento Completo do Exoma
3.
Exp Ther Med ; 18(3): 2346-2352, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452718

RESUMO

The present study attempted to determine the correlation of the degree of coronary artery stenosis and Tolllike receptor 2/4 (TLR2/4) levels in Chinese Zhuang patients with coronary heart disease (CHD). A total of 466 Chinese patients from the Zhuang Ethnic population diagnosed with CHD at the Department of Cardiology the Affiliated Hospital of Youjiang Medical University between January 2016 and August 2017, together with 102 control patients, were recruited for the present study. The patients with CHD were divided into three groups depending on the number of diseased arteries. The patients with CHD were also classified according to their Gensini scores. Blood liver and renal function parameters, as well as blood sugar and lipid levels were measured. ELISA was used for TLR2/4 measurements. There were no significant differences with gender, age and body mass index between the CHD and control groups. The levels of TLR2/4 in the peripheral blood of the control and CHD groups were 2.34±0.85/5.08±2.41 and 5.22±3.16/9.33±4.92 ng/ml, respectively, and the differences were significant (P<0.001). Analysis of the three subgroups of vessel disease indicated that the expression of TLR2/4 was progressively higher with the increase in the number of affected vessels (P<0.01). There were also significant differences between the mild, moderate and severe stenosis groups (P<0.01). A positive linear correlation between TLR2/4 and the Gensini coronary artery score was identified (r=0.508 and 0.346, respectively; P<0.0001). In conclusion, the present study determined a positive correlation between the degree of coronary artery stenosis and the expression level of TLR2/4 in the serum of Chinese Zhuang patients with CHD. Serum TLR2/4 may be used to predict the severity of CHD.

4.
Gene ; 708: 1-9, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31082501

RESUMO

OBJECTIVES: Toll-like receptor 4 (TLR4) is known to be involved in the innate immunity and inflammatory responses that plays a crucial role in the pathogenesis of coronary artery disease (CAD). This study aimed to examine the potential relationship of TLR4 polymorphisms and serum TLR4 protein levels and the risk of CAD in the ethnic Zhuang population of China. METHODS: 1171 serum samples were collected from Zhuang patients, including 556 CAD cases (≥50% luminal stenosis of any coronary vessel) and 615 normal healthy controls (subjects with no luminal stenosis in coronary arteries). Detection of TLR4 polymorphisms was by single base extension polymerase chain reaction (Snapshot PCR) and DNA sequencing (rs11536879A/G and rs11536889G/C) gene sequence in all subjects. Serum TLR4 protein concentrations was measured by ELISA. RESULTS: There are significant differences in the allele and genotype frequencies of TLR4 gene rs11536889 between Chinese Zhuang CAD patients and controls, especially in the males. Male carriers of rs11536879 andrs11536889 variant alleles show an increased risk of CAD compared to non-carriers. Serum TLR4 protein levels of CAD patients are higher than controls and the levels tended to increase with the number of coronary artery lesions. Serum TLR4 protein levels of CAD patients showed no correlation with rs11536879 and rs11536889 polymorphisms. CONCLUSIONS: The rs11536879 and rs11536889 polymorphisms of TLR4 gene and serum TLR4 protein levels may contribute to the occurrence and development of CAD. However, the rs11536879 and rs11536889 polymorphisms have no significant effects on the expression of serum TLR4 protein in Zhuang patients with CAD.


Assuntos
Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Receptor 4 Toll-Like/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Receptor 4 Toll-Like/sangue
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