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1.
Electron. j. biotechnol ; 52: 1-12, July. 2021. tab, ilus, graf
Article in English | LILACS | ID: biblio-1283167

ABSTRACT

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a neoplasm of B-cells characterized by variable prognosis. Exploring the proteome of CLL cells may provide insights into the disease. Therefore, eleven proteomics experiments were conducted on eleven primary CLL samples. RESULTS: We reported a CLL proteome consisting of 919 proteins (false discovery rate (FDR) 1%) whose identification was based on the sequencing of two or more distinct peptides (FDR of peptide sequencing 1%). Mass spectrometry-based protein identification was validated for four different proteins using Western blotting and specific antibodies in different CLL samples. Small sizes of nucleolin (~57 kDa and ~68 kDa) showed a potential association with good prognosis CLL cells (n = 8, p < 0.01). Compared with normal B-cells, CLL cells over-expressed thyroid hormone receptor-associated protein 3 (THRAP3; n = 9; p = 0.00007), which is implicated in cell proliferation; and heterochromatin protein 1-binding protein 3 (HP1BP3; n = 10; p = 0.0002), which promotes cell survival and tumourogenesis. A smaller form of HP1BP3, which may correspond to HP1BP3 isoform-2, was specifically identified in normal B-cells (n = 10; p = 0.0001). HP1BP3 and THRAP3 predicted poor prognosis of CLL (p 0.05). Consistently, THRAP3 and HP1BP3 were found to be associated with cancer-related pathways (p 0.05). CONCLUSIONS: Our findings add to the known proteome of CLL and confirm the prognostic importance of two novel cancer-associated proteins in this disease.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Biomarkers, Tumor/analysis , Mass Spectrometry , Transcription Factors/analysis , Nuclear Proteins/analysis , Blotting, Western , Chromatography, Liquid , Proteomics , DNA-Binding Proteins/analysis
2.
Braz. j. med. biol. res ; 54(11): e11396, 2021. graf
Article in English | LILACS | ID: biblio-1339444

ABSTRACT

Current understanding of the genetic factors contributing to the etiology of non-syndromic craniosynostosis (NSC) remains scarce. The present work investigated the presence of variants in ALX4, EFNA4, and TWIST1 genes in children with NSC to verify if variants within these genes may contribute to the occurrence of these abnormal phenotypes. A total of 101 children (aged 45.07±40.94 months) with NSC participated in this cross-sectional study. Parents and siblings of the probands were invited to participate. Medical and family history of craniosynostosis were documented. Biological samples were collected to obtain genomic DNA. Coding exons of human TWIST1, ALX4, and EFNA4 genes were amplified by polymerase chain reaction and Sanger sequenced. Five missense variants were identified in ALX4 in children with bilateral coronal, sagittal, and metopic synostosis. A de novo ALX4 variant, c.799G>A: p.Ala267Thr, was identified in a proband with sagittal synostosis. Three missense variants were identified in the EFNA4 gene in children with metopic and sagittal synostosis. A TWIST1 variant occurred in a child with unilateral coronal synostosis. Variants were predicted to be among the 0.1% (TWIST1, c.380C>A: p. Ala127Glu) and 1% (ALX4, c.769C>T: p.Arg257Cys, c.799G>A: p.Ala267Thr, c.929G>A: p.Gly310Asp; EFNA4, c.178C>T: p.His60Tyr, C.283A>G: p.Lys95Glu, c.349C>A: Pro117Thr) most deleterious variants in the human genome. With the exception of ALX4, c.799G>A: p.Ala267Thr, all other variants were present in at least one non-affected family member, suggesting incomplete penetrance. Thus, these variants may contribute to the development of craniosynostosis, and should not be discarded as potential candidate genes in the diagnosis of this condition.


Subject(s)
Humans , Child , Craniosynostoses/genetics , Transcription Factors/genetics , Base Sequence , Family , Cross-Sectional Studies , Mutation, Missense/genetics , DNA-Binding Proteins/genetics
3.
Frontiers of Medicine ; (4): 91-100, 2021.
Article in English | WPRIM | ID: wpr-880951

ABSTRACT

Congenital heart disease (CHD) is the most common birth defect worldwide. Long non-coding RNAs (lncRNAs) have been implicated in many diseases. However, their involvement in CHD is not well understood. This study aimed to investigate the role of dysregulated lncRNAs in CHD. We used Gene Expression Omnibus data mining, bioinformatics analysis, and analysis of clinical tissue samples and observed that the novel lncRNA SAP30-2:1 with unknown function was significantly downregulated in damaged cardiac tissues from patients with CHD. Knockdown of lncRNA SAP30-2:1 inhibited the proliferation of human embryonic kidney and AC16 cells and decreased the expression of heart and neural crest derivatives expressed 2 (HAND2). Moreover, lncRNA SAP30-2:1 was associated with HAND2 by RNA immunoprecipitation. Overall, these results suggest that lncRNA SAP30-2:1 may be involved in heart development through affecting cell proliferation via targeting HAND2 and may thus represent a novel therapeutic target for CHD.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Cell Proliferation , Heart Defects, Congenital/genetics , Histone Deacetylases , Humans , RNA, Long Noncoding/genetics , Transcription Factors
4.
Article in Chinese | WPRIM | ID: wpr-880127

ABSTRACT

Sickle cell disease (SCD) is a single gene genetic disease, which seriously threatens the life span and quality of patients. On the basis of the pathogenesis of SCD and the alternative therapy based on fetal hemoglobin F (HbF), the research progress of transcription factors involved in the regulation of HbF gene expression, such as BCL11A, ZBTB7A, KLF-1, c-MYB and SOX6, as well as the application of CRISPR / Cas9, TALEN, zinc finger nuclease and other gene editing technologies in this field has been made, providing a solid theoretical basis for the exploration of new treatment schemes for β- like hemoglobin diseases, such as sickle cell disease and β- thalassemia.


Subject(s)
Anemia, Sickle Cell/therapy , Cell Line, Tumor , DNA-Binding Proteins , Fetal Hemoglobin/genetics , Genetic Therapy , Humans , Repressor Proteins/genetics , Transcription Factors
5.
Article in Chinese | WPRIM | ID: wpr-880096

ABSTRACT

OBJECTIVE@#To investigate the relationship between acute myeloid leukemia (AML) patients ASXL2, ZBTB7A gene mutations and the prognosis.@*METHODS@#42 AML Patients treated in our hospital from January 2014 to January 2016 were selected and ASXL2 and ZBTB7A genes of their bone marrow samples were sequenced, the genetic characteristics and prognosis of core-binding factor-AML(CBF-AML) patients with ASXL2 and ZBTB7A mutations were analyzed.@*RESULTS@#ASXL2 (33.3%) and ZBTB7A (9.5%) mutations were found in t (8; 21) AML patients. Compared with wild-type, patients with ASXL2 mutations showed significantly higher white blood cell count at diagnosis [(9.49±1.85)×10@*CONCLUSION@#ASXL2 and ZBTB7A mutations are frequently found in t (8; 21) AML patients. The mutation of ASXL2 and ZBTB7A genes shows no significant effect on the prognosis of AML patients.


Subject(s)
Cell Line, Tumor , DNA-Binding Proteins/genetics , Humans , Leukemia, Myeloid, Acute/genetics , Mutation , Oncogene Proteins, Fusion/genetics , Prognosis , Repressor Proteins/genetics , Transcription Factors/genetics
6.
Article in Chinese | WPRIM | ID: wpr-879853

ABSTRACT

Neural development is regulated by both external environment and internal signals, and in addition to transcription factors, epigenetic modifications also play an important role. By focusing on the genetic mechanism of ATP-dependent chromatin remodeling in children with neurodevelopmental disorders, this article elaborates on the effect of four chromatin remodeling complexes on neurogenesis and the development and maturation of neurons and neuroglial cells and introduces the clinical research advances in neurodevelopmental disorders.


Subject(s)
Child , Chromatin , Chromatin Assembly and Disassembly , Humans , Neurodevelopmental Disorders/genetics , Neurogenesis , Transcription Factors/genetics
7.
Article in Chinese | WPRIM | ID: wpr-879091

ABSTRACT

NAC(NAM/ATAF/CUC) protein plays an important role in plant growth and development, secondary cell wall formation and stress response. In this study, based on the sequencing data of Angelica dahurica, the NAC family was systematically analyzed using bioinformatics methods and its expression pattern was analyzed. Studies showed that 75 candidate genes had been selected from the NAC transcription factor family of A. dahurica, with the protein size of 148-641, all of which were unstable hydrophilic proteins. Most NAC proteins were localized in the nucleus, and had complete NAC domain. Phylogenetic analysis of NAC family proteins of A.dahurica and Arabidopsis thaliana showed that among the 17 subfamilies, NAC members were unevenly distributed in each subfamily, indicating that the evolution of species is developing in multiple directions. Among them, ANAC063 subfamily contained no NAC sequence of A. dahurica, which might be due to the functional evolution of the species. Analysis of protein transmembrane structure and signal peptide showed that NAC transcription factor could carry out transmembrane transportation, but its signal peptide function had not been found. Expression analysis showed that most transcription factors responded to abiotic stress and hormones to varying degrees, and the effects of hormones were obvious, especially ABA and IAA. In different organs of A. dahurica, most members of the NAC family had higher expression in root phloem, followed by root xylem. This study lays a foundation for further research on the function of A. dahurica NAC transcription factor and for solving the biological problems of A. dahurica.


Subject(s)
Angelica , Computational Biology , Gene Expression Regulation, Plant , Phylogeny , Plant Proteins/metabolism , Stress, Physiological , Transcription Factors/metabolism
8.
Article in Chinese | WPRIM | ID: wpr-878916

ABSTRACT

This study cloned the transcription factor gene PnbHLH which held an open reading frame of 966 bp encoding 321 amino acids. This study constructed the overexpression vector of transcription factor PnbHLH of Panax notoginseng. The combination of PnbHLH overexpression and RNAi of the key enzyme gene PnCAS involved in the phytosterol biosynthesis was achieved in P. notoginseng cells, thus exploring the biosynthetic regulation of P. notoginseng saponins(PNS) by the synergistic effect of PnbHLH overexpression and PnCAS RNAi. The results showed that the PnbHLH transcription factor interacted with the promoters of key enzyme genes PnDS, PnSS and PnSE in the biosynthetic pathway of PNS, and then regulated the expression levels of key enzyme genes and affected the biosynthesis of saponins indirectly. Further study indicated that the synergistic effect of PnbHLH overexpression and PnCAS RNAi was a more effective approach to regulate the biosynthesis of saponins. Compared with the wild type and PnCAS RNAi cells of P. notoginseng, the contents of total saponins and monomeric saponins(Rd, Rb_1, Re, Rg_1 and R_1) were increased to some extent in the cell lines of PnbHLH overexpression and PnCAS RNAi. This indicated that the two ways of forward regulation and reverse regulation of saponin biosynthesis showed superposition effect. This study explored a more rational and efficient regulation strategy of PNS biosynthesis based on the advantages of multi-point regulation of transcription factors as well as the down-regulation of by-product synthesis of saponins.


Subject(s)
Intramolecular Transferases , Panax notoginseng , RNA Interference , Saponins , Transcription Factors/genetics
9.
Article in Chinese | WPRIM | ID: wpr-878693

ABSTRACT

Objective To summarize clinical characteristics and investigate possible pathogenic gene of Klippel-Feil syndrome(KFS)by the self-designed multigene panel sequencing,so as to decipher the molecular basis for early diagnosis and targeted therapy.Methods From January 2015 to December 2018,we consecutively recruited 25 patients who were diagnosed with KFS in Peking Union Medical College Hospital.The demographic information,clinical manifestations,physical examination and radiological assessments were analyzed.Multigene panel sequencing was performed after DNA extraction from peripheral blood.The possible pathogenic mutations of KFS were explored on the basis of bioinformatics analysis.Results The KFS cohort consisted of 25 patients,including 15 males and 10 females,with a mean age of(12.9±7.3)years.Limited cervical range of motion was the most common clinical feature(12 cases,48%).Based on the Samartzis classification,the proportion of patients suffered from short neck(P=0.031)and limited cervical range of motion(P=0.026)in type Ⅲ KFS was significantly higher than that in type Ⅱ and type Ⅰ KFS.Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients,including COL6A1,COL6A2,CDAN1,GLI3,FLNB,CHRNG,MYH3,POR,and TNXB.There was no pathogenic mutation found in five reported pathogenic genes(GDF6,MEOX1,GDF3,MYO18B and RIPPLY2)associated with KFS.Conclusions Our study has shown that patients with multiple contiguous cervical fusions are more likely to manifest short neck,limited cervical range of motion,and clinical triad.Therefore,these patients need additional attention and follow-up.Our analysis highlights novel KFS-related genetic variants,such as COL6A and CDAN1,extending the spectrum of known mutations contributing to this syndrome and providing a basis for elucidating the pathogenesis of KFS.


Subject(s)
Cervical Vertebrae , Child , Cohort Studies , Female , Glycoproteins , Humans , Klippel-Feil Syndrome/genetics , Male , Mutation , Nuclear Proteins , Radiography , Transcription Factors/genetics
10.
Chinese Journal of Biotechnology ; (12): 1155-1167, 2021.
Article in Chinese | WPRIM | ID: wpr-878621

ABSTRACT

With the constant change of global climate, plants are often affected by multiple abiotic stresses such as heat stress, drought stress, cold stress and saline-alkali stress. Heat shock transcription factors (HSFs) are a class of transcription factors widely existing in plants to respond to a variety of abiotic stresses. In this article, we review and summarize the structure, signal regulation mechanism of HSFs and some research in plants like Arabidopsis thaliana, tomato, rice and soybean, to provide reference for further elucidating the role of HSFs in the stress regulation network.


Subject(s)
Arabidopsis/metabolism , Droughts , Gene Expression Regulation, Plant , Heat Shock Transcription Factors/genetics , Plant Proteins/genetics , Stress, Physiological , Transcription Factors/metabolism
11.
Chinese Journal of Biotechnology ; (12): 911-922, 2021.
Article in Chinese | WPRIM | ID: wpr-878603

ABSTRACT

Transcription factor-based biosensors (TFBs) play an essential role in metabolic engineering and synthetic biology. TFBs sense the metabolite concentration signals and convert them into specific signal output. They hold high sensitivity, strong specificity, brief analysis speed, and are widely used in response to target metabolites. Here we reviewe the principles of TFBs, the application examples, and challenges faced in recent years in microbial cells, including detecting target metabolite concentrations, high-throughput screening, adaptive laboratory evolutionary selection, and dynamic control. Simultaneously, to overcome the challenges in the application, we also focus on reviewing the performance tuning strategies of TFBs, mainly including traditional and computer-aided tuning strategies. We also discuss the opportunities and challenges that TFBs may face in practical applications, and propose the future research trend.


Subject(s)
Biosensing Techniques , Gene Expression Regulation , Metabolic Engineering , Synthetic Biology , Transcription Factors/metabolism
12.
Chinese Journal of Biotechnology ; (12): 500-512, 2021.
Article in Chinese | WPRIM | ID: wpr-878578

ABSTRACT

Metabolic syndrome is a global chronic epidemic. Its pathogenesis is determined by genetic and environmental factors. Epigenetic modification is reported to regulate gene expression without altering its nucleotide sequences. In recent years, epigenetic modification is sensitively responded to environmental signals, further affecting the gene expression and signaling transduction. Among these regulators, chromatin remodeling SWI/SNF (SWItch/Sucrose non fermentable, SWI/SNF) complex subunit Baf60a plays an important role in maintaining energy homeostasis in mammals. In this paper, we described the pathophysiological roles of Baf60a in maintaining the balance of energy metabolism, including lipid metabolism, cholesterol metabolism, urea metabolism, as well as their rhythmicity. Therefore, in-depth understanding of Baf60a-orchestrated transcriptional network of energy metabolism will provide potential therapeutic targets and reliable theoretical supports for the treatment of metabolic syndrome.


Subject(s)
Animals , Energy Metabolism/genetics , Homeostasis , Lipid Metabolism , Signal Transduction , Transcription Factors/metabolism
13.
Chinese Journal of Biotechnology ; (12): 142-148, 2021.
Article in Chinese | WPRIM | ID: wpr-878549

ABSTRACT

WRKY transcription factors are one of the largest families of transcription factors in higher plants and involved in regulating multiple and complex growth and development processes in plants. WRKY12 is a typical member of WRKY family. This article summarizes recent research progresses on the regulatory mechanism of WRKY12 in multiple growth and development processes, and analyzes the functional differences between WRKY12 and WRKY13. It provides a useful reference for further studying the molecular mechanism of WRKY12 in plant complex developments. It also provides clearer research ideas and reference strategies for exploring the self-regulation of other WRKY member and the mutual regulatory relationships between different WRKY family genes.


Subject(s)
Gene Expression Regulation, Plant , Humans , Phylogeny , Plant Development/genetics , Plant Proteins/metabolism , Plants/metabolism , Stress, Physiological , Transcription Factors/metabolism
14.
Acta Physiologica Sinica ; (6): 217-222, 2021.
Article in English | WPRIM | ID: wpr-878250

ABSTRACT

Accumulating evidence demonstrates that the nucleus tractus solitarii (NTS) neurons serve as central respiratory chemoreceptors, but the underlying molecular mechanisms remain undefined. The present study investigated the expression of acid-sensitive ether-à-go-go-gene-like (Elk, Kv12) channels in the NTS of mice. Immunofluorescence staining was used to observe the distribution and cellular localization of the Kv12 channels in NTS neurons. Western blot and quantitative real-time PCR (qPCR) were used to evaluate protein and mRNA expression levels of Kv12 channels. The results showed that all of the three members (Kv12.1, Kv12.2, Kv12.3) of the Kv12 channel family were expressed in NTS neurons, and their expressions were co-localized with paired-like homeobox 2b gene (Phox2b) expression. The expression of Kv12.1 mRNA was the largest, whereas the expression of Kv12.3 was the least in the NTS. The results suggest Kv12 channels are expressed in Phox2b-expressing neurons in the NTS of mice, which provides molecular evidence for pH sensitivity in Phox2b-expressing NTS neurons.


Subject(s)
Animals , Mice , Neurons , Potassium Channels, Voltage-Gated , Solitary Nucleus , Transcription Factors/genetics
15.
Chinese Medical Journal ; (24): 1017-1030, 2021.
Article in English | WPRIM | ID: wpr-878138

ABSTRACT

The LIM domain only 1 (LMO1) gene belongs to the LMO family of genes that encodes a group of transcriptional cofactors. This group of transcriptional cofactors regulates gene transcription by acting as a key "connector" or "scaffold" in transcription complexes. All LMOs, including LMO1, are important players in the process of tumorigenesis. Unique biological features of LMO1 distinct from other LMO members, such as its tissue-specific expression patterns, interacting proteins, and transcriptional targets, have been increasingly recognized. Studies indicated that LMO1 plays a critical oncogenic role in various types of cancers, including T-cell acute lymphoblastic leukemia, neuroblastoma, gastric cancer, lung cancer, and prostate cancer. The molecular mechanisms underlying such functions of LMO1 have also been investigated, but they are currently far from being fully elucidated. Here, we focus on reviewing the current findings on the role of LMO1 in tumorigenesis, the mechanisms of its oncogenic action, and the mechanisms that drive its aberrant activation in cancers. We also briefly review its roles in the development process and non-cancer diseases. Finally, we discuss the remaining questions and future investigations required for promoting the translation of laboratory findings to clinical applications, including cancer diagnosis and treatment.


Subject(s)
Carcinogenesis/genetics , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Humans , LIM Domain Proteins/genetics , Male , Transcription Factors/metabolism
16.
Article in Chinese | WPRIM | ID: wpr-879570

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child affected with Bainbridge-Ropers syndrome.@*METHODS@#Genomic DNA was extracted from peripheral venous blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out to detect genetic variant of the proband. Candidate variant was verified by Sanger sequencing.@*RESULTS@#The 3-year-old boy presented with psychomotor retardation, linguistic difficulties, mental retardation and peculiar craniofacial phenotype. A de novo heterozygous nonsense variant of the ASXL3 gene, c.3106C>T, was identified by WES in the proband, and the same mutation was not found among his parents. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.3106C>T variant was predicted to be pathogenic (PVS1+PS2+PP4).@*CONCLUSION@#The heterozygous variant c.3106C>T of the ASXL3 gene probably underlies the Bainbridge-Ropers syndrome in the patient. Above result has enabled the clinical diagnosis and genetic counseling for the family.


Subject(s)
Child , Child, Preschool , Heterozygote , Humans , Intellectual Disability/genetics , Male , Mutation , Phenotype , Transcription Factors/genetics , Whole Exome Sequencing
17.
Article in Chinese | WPRIM | ID: wpr-879542

ABSTRACT

OBJECTIVE@#To explore the genetic etiology for a newborn with corneal opacity.@*METHODS@#The neonate and her parents were subjected to routine G-banding chromosomal karyotyping analysis. Copy number variation (CNV) was analyzed with low-coverage whole-genome sequencing (WGS) and single nucleotide polymorphism microarray (SNP array).@*RESULTS@#No karyotypic abnormality was found in the newborn and her parents. Low-coverage WGS has identified a de novo 5.5 Mb microdeletion at chromosome 8q21.11-q21.13 in the neonate, which encompassed the ZFHX4 and PEX2 genes. The result was confirmed by SNP array-based CNV analysis.@*CONCLUSION@#The newborn was diagnosed with chromosome 8q21.11 deletion syndrome. ZFHX4 may be one of the key genes underlying this syndrome.


Subject(s)
Chromosome Banding , Chromosomes, Human, Pair 8/genetics , DNA Copy Number Variations , Female , Genetic Testing , Homeodomain Proteins/genetics , Humans , Infant, Newborn , Karyotyping , Monosomy/genetics , Peroxisomal Biogenesis Factor 2/genetics , Polymorphism, Single Nucleotide , Transcription Factors/genetics
18.
Electron. j. biotechnol ; 47: 17-28, sept. 2020. ilus, graf
Article in English | LILACS | ID: biblio-1253006

ABSTRACT

BACKGROUND: Cichoric acid (CA) is extracted from Echinacea purpurea. It is well known and widely used for its immunological function. However, the effect of CA on peripheral blood mononuclear cells (PBMCs) from yaks is still unclear. This study investigated the potential influences of CA on the proliferation, cytokine induction, and apoptosis of PBMCs from Datong yak in vivo, and aimed to provide a basis for exploring the pharmacological activities of CA on yaks. RESULTS: In this study, CA promoted PBMCs proliferation by combining concanavalin A (Con A) and exhibited a dose-dependent effect as demonstrated by a Cell Counting Kit-8. The concentration of 60 µg/ml CA was the best and promoted the transformation from the G0/G1 phase to the S and G2/M phases with Con A. Furthermore, 60 µg/ml CA significantly increased IL-2, IL-6, and IFN-γ levels and PCNA, CDK4 and Bcl-2 expression levels, but it significantly inhibited the TP53, Bax, and Caspase-3 expression levels. Transcriptome analysis revealed a total of 6807 differentially expressed genes (DEGs) between the CA treatment and control groups. Of these genes, 3788 were significantly upregulated and 3019 were downregulated. Gene Ontology and pathway analysis revealed that DEGs were enriched in cell proliferation and immune function signaling pathways. The expression level of some transcription factors (BTB, Ras, RRM_1, and zf-C2H2) and genes (CCNF, CCND1, and CDK4) related to PBMCs proliferation in yaks were significantly promoted after CA treatment. By contrast, anti-proliferation-associated genes (TP53 and CDKN1A) were inhibited. CONCLUSIONS: In summary, CA could regulate the immune function of yaks by promoting proliferation and inhibiting inflammation and apoptosis of PBMCs.


Subject(s)
Animals , Cattle , Succinates/pharmacology , Caffeic Acids/pharmacology , Leukocytes, Mononuclear/drug effects , Echinacea/chemistry , Cell Proliferation/drug effects , Transcription Factors , Enzyme-Linked Immunosorbent Assay , Leukocytes, Mononuclear/cytology , Blotting, Western , Cytokines , Apoptosis/drug effects , Concanavalin A/pharmacology , Real-Time Polymerase Chain Reaction , RNA-Seq
19.
Braz. j. otorhinolaryngol. (Impr.) ; 86(3): 370-375, May-June 2020. tab, graf
Article in English | LILACS | ID: biblio-1132588

ABSTRACT

Abstract Instruction: Noise-induced hearing loss is a leading occupational disease caused by gene-environment interaction. The Grainy Like 2, GRHL2, is a candidate gene. In this regard, many studies have evaluated the association between GRHL2 and noise-induced hearing loss, although the results are ambiguous and conflicting. Objective: The purpose of this study was to identify a precise estimation of the association between rs3735715 polymorphism in GRHL2 gene and susceptibility of noise-induced hearing loss. Methods: A comprehensive search was performed to collect data up to July 8, 2018. Finally, 4 eligible articles were included in this meta-analysis comprising 2410 subjects. The pooled odds ratios with 95% confidence intervals were used to evaluate the strength of the association. Results: Significant association was found in the overall population in the dominant model (GA/AA vs. GG, odds ratio = 0.707, 95% confidence interval = 0.594-0.841) and allele model (G allele vs. A allele, odds ratio = 1.189, 95% confidence interval = 1.062-1.333). When stratified by source of the subjects, we also found association between rs3735715 and noise-induced hearing loss risk in the dominant model (GA/AA vs. GG, odds ratio = 0.634, 95% confidence interval = 0.514-0.783) and allele model (G allele vs. A allele, odds ratio = 1.206, 95% confidence interval = 1.054-1.379). Conclusion: Rs3735715 polymorphism in GRHL2 gene may influence the susceptibility of noise-induced hearing loss. Additional large, well-designed and functional studies are needed to confirm this association in different populations.


Resumo Introdução: Perda auditiva induzida por ruído é uma das principais doenças ocupacionais causadas pela interação gene-ambiente. O Grainy Like 2, ou GRHL2 é um gene que tem sido considerado como candidato. Nesse sentido, muitos estudos avaliaram a associação entre o GRHL2 e perda auditiva induzida por ruído, embora os resultados sejam ambíguos e conflitantes. Objetivo: Identificar uma estimativa precisa da associação entre o polimorfismo rs3735715 no gene GRHL2 e a suscetibilidade à perda auditiva induzida por ruído. Método: Uma pesquisa abrangente foi feita para coletar dados até 8 de julho de 2018. No fim, quatro artigos elegíveis foram incluídos nesta metanálise, abrangeram 2.410 indivíduos. As odds ratios agrupadas com intervalos de confiança de 95% foram usadas para avaliar a força da associação. Resultados: Uma associação significante foi encontrada na população geral no modelo de dominância (GA/AA vs. GG, odds ratio = 0,707, intervalo de confiança 95% = 0,594-0,841) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,189, intervalo de confiança 95% = 1,062 a 1,333). Quando estratificados pelo local de trabalho dos indivíduos, também encontramos associação entre rs3735715 e risco de perda auditiva induzida por ruído no modelo de dominância (GA/AA vs. GG, odds ratio = 0,634, intervalo de confiança 95% = 0,514 ± 0,783) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,206, intervalo de confiança 95% = 1,054- 1,379). Conclusão: O polimorfismo Rs3735715 no gene GRHL2 pode influenciar a suscetibilidade à perda auditiva induzida por ruído. Estudos adicionais, amplos, bem desenhados e funcionais são necessários para confirmar essa associação em diferentes populações.


Subject(s)
Humans , Transcription Factors/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , DNA-Binding Proteins/genetics , Hearing Loss, Noise-Induced/genetics , Genotype , Noise, Occupational/adverse effects , Occupational Diseases/genetics
20.
Electron. j. biotechnol ; 45: 53-59, May 15, 2020. tab, ilus
Article in English | LILACS | ID: biblio-1177447

ABSTRACT

BACKGROUND: Helicobacter pylori is a chronic pathogenic bacteria that causes gastric mucosal damage through various host-related and pathogen-related factors. Thus, a single gene research cannot fully explain its pathogenicity. PURPOSE OF STUDY: It is necessary to establish a Helicobacter pylori pathogenic gene transcription factor regulatory network (TFRN) and study its central nodes. RESULTS: The expression data of Helicobacter pylori pathogenic genes were obtained through GEO Datasets of NCBI. The genes were screened using linear model-empirical Bayesian statistics in R language Limma package combined with the conventional t-test; the results identified 1231 differentially expressed genes. The functional analysis (gene ontology-analysis) and signal pathway analysis (pathway-analysis) of differentially expressed genes were performed using the DAVID and KEGG databases, respectively. The pathogenic gene regulatory network was constructed by integrating transcriptional regulatory element database (TRED); the disease-related analysis of the pathogenic genes was conducted using the DAVID annotation tool. Five pathogenic genes (Nos2, Il5, Colla1, Tnf, and Nfkb1) and their transcription factors (Jun, Cebpa, Egrl, Ppara, and Il6) were found to suppress the host immune function and enhance the pathogenicity of Helicobacter pylori by regulating the host immune system. CONCLUSIONS: This effect was largely mediated via three signaling pathways: Tnf pathway, PI3K Akt pathway, and Jak­STAT pathway. The pathogenicity of Helicobacter pylori is closely related to the body's immune and inflammatory system. A better understanding of the correlation of the pathogenic factors with the host immune and inflammatory factors may help to determine the precise pathogenic mechanism of H. pylori infection.


Subject(s)
Helicobacter pylori/genetics , Helicobacter pylori/pathogenicity , Computational Biology , Transcription Factors , Cytokines , Virulence Factors , Gastritis/immunology , Gastritis/microbiology , Genes, Bacterial , Immune System , Inflammation
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