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1.
Artif Cells Nanomed Biotechnol ; 48(1): 276-287, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31858826

RESUMO

Background: The abnormal expression Dopamine D1 receptor (DRD1) gives rise to the dysfunction of dopaminergic neurotransmitter and may be associated with the occurrence of schizophrenia. MicroRNAs (miRNAs) can regulate the DRD1 expression by binding 3'UTR and be involved in the post-transcriptional regulation.Methods: We first constructed the pmirGLO-recombined vectors of series of DRD1 gene 3'UTR-truncated fragments and performed the luciferase receptor assay to screen the underlying 3'UTR sequence targeted by miRNAs. Then, we predicted the potential miRNAs binding the target sequence and confirmed their effects using luciferase receptor assay after transfection of the miRNA mimics/inhibitors. We also examined the effects of the miRNA on the endogenous DRD1 expression.Results: We found that the DRD1 3'UTR ranging from -12 to +1135 bp was essential for the post-transcriptional regulation of miRNAs. The deletion of -12 to +154 bp fragment significantly increased the luciferase expression but not the mRNA expression. The miRNA-15a, miRNA-15b and miRNA 16 affected DRD1 expression in HEK293, U87, SK-N-SH and SH-SY5Y cell lines.Conclusion: The miRNA-15a, miRNA-15b and miRNA-16 inhibit the human dopamine D1 receptor expression by targeting 3'UTR -12 to +154 bp.HighlightsDRD1 3'UTR ranging from -12 to +1135 bp was essential for the post-transcriptional regulation of miRNAs.The deletion of -12 to +154 bp fragment significantly increased the luciferase expression but not the mRNA expression.The miRNA-15a, miRNA-15b and miRNA 16 affected DRD1 expression in different cell lines, respectively.

2.
Genes (Basel) ; 10(10)2019 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-31614865

RESUMO

This study identified a transcription factor that might bind to the 5' regulatory region of the HTR1A and explored the potential effect on 5-HT1A receptor expression. Based on JASPAR predictions, the binding of the transcription factor was demonstrated using the electrophoretic mobility shift assay (EMSA). Vectors over-expressing the transcription factor were co-transfected into HEK-293 and SK-N-SH cells with the recombinant pGL3 vector, and relative fluorescence intensity was measured to determine regulatory activity. Additionally, the qRT-PCR and Western blot were also used to identify whether the transcription factor modulated the endogenous expression of 5-HT1A receptor. The results suggest that the transcription factor CCAA/T enhancer binding protein beta (CEBPB) likely binds to the -1219 to -1209 bp (ATG+1) region of the HTR1A. Two sequences located in the -722 to -372 bp and -119 to +99 bp were also identified. Although the effect of CEBPB on endogenous 5-HT1A receptor expression was not significant, it exhibited the strong inhibition on the relative fluorescence intensity and the mRNA level of HTR1A. CEBPB inhibited the human HTR1A expression by binding to the sequence -1219 - -1209 bp. This is useful and informative for ascertaining the regulation of 5-HT1A receptor and mental diseases.

3.
Mol Genet Genomic Med ; 7(11): e984, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566932

RESUMO

BACKGROUND: It is meaningful to expand the available population information on forensic medicine and to investigate the genetic characteristics of Han population from Jilin Province, Northeast China. METHODS: In this study, we investigated the genetic characteristics of 24 Y-chromosomal short tandem repeat (STR) loci in 1,088 unrelated Chinese Han male individuals from Jilin Province, using DNATyperTM Y24 amplification kit. Additionally, we performed the population comparison between the Jilin population and the other nine reported populations based on the Y-STR genotyping haplotypes. RESULTS: A total of 1,067 different haplotypes were found from 1,088 unrelated individuals, of which 1,046 were unique and 21 were shared by two individuals. The gene diversity values of 22 loci ranged from 0.3870 (DYS391) to 0.9668 (DYS385ab). The random match probability was 0.0010 with the discrimination capacity of 0.9807. Population comparison showed that there were minor differences compared to Beijing Chinese Han, China Manchu, Gansu Chinese Han, and Jiangsu Chinese Han, but major differences with respect to the populations of Guangdong Chinese Han, Yunnan Chinese Han, China Hui, China Korean, and China Tibetan. CONCLUSION: Our results showed that the 24 Y-STR loci in Jilin Han population are valuable for forensic application and human genetics.

4.
Neurosci Lett ; 713: 134535, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31586698

RESUMO

The Schizophrenia Psychiatric GWAS Consortium (PGC) has identified the rs1625579 polymorphism in the MIR137 gene, which encodes miR-137, as the strongest new association with schizophrenia in the European population. However, whether the influence of rs1625579 on schizophrenia in the Asian population is consistent with these results remains unclear. A total of 21 studies (9878 schizophrenic patients and 9447 control subjects) that met the inclusion criteria were included in our meta-analysis. Pooled analysis, subgroup analysis, sensitivity analysis and publication bias were performed. The T allele, TT genotype and TT + GG genotype were associated with schizophrenia as risk factors. Subgroup analysis shows that no heterogeneity existed in the European and Asian populations. Our meta-analysis found that the Rs1625579 polymorphism in the MIR137 gene was associated with the risk of schizophrenia. The current findings provide a reference for case-control studies of schizophrenia in the future.

5.
J Mol Neurosci ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31440993

RESUMO

The dopamine transporter is coded by the SLC6A3 gene and plays an important role in regulation of the neurotransmitter dopamine. To detect the association between the SLC6A3 gene and the risk of schizophrenia, 31 case-control articles were included in this meta-analysis. There were 23 studies with 40 bp VNTR (3246 cases and 3639 controls), 4 studies with rs40184 (2020 cases and 1674 controls), rs6347 (1317 cases and 1917 controls), rs403636 (2045 cases and 1704 controls), and rs2975226 (849 cases and 904 controls); and 3 studies with rs12516948 (1920 cases and 1569 controls), rs27072 (984 cases and 1015 controls), rs6869645 (1142 cases and 1082 controls), rs37022 (1168 cases and 1091 controls), rs464049 (1169cases and 1096 controls), rs2652511 (707 cases and 714 controls), and rs3756450 (1176 cases and 1096 controls). Pooled, subgroup, and sensitivity analyses were performed, and the results were visualized by forest and funnel plots. In the dominant genetic model, the genotype AA+AT of rs2975226 in the Indian population (Pz = 0, odds ratio [OR] = 3.245, 95% confidence interval [CI] = 1.806-5.831), TT of rs464049 (Pz = 0.002, OR = 1.389, 95% CI = 1.129-1.708), and TT of rs3756450 (Pz = 0.014, OR = 1.251, 95% CI = 1.047-1.495) might be risk factors for schizophrenia. Additionally, no other single nucleotide polymorphisms were observed. These results indicate that more functional studies are warranted.

7.
Mol Genet Genomic Med ; 7(5): e652, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30908890

RESUMO

BACKGROUND: This study investigated the effects of haplotypes T-G and C-A derived from NG_012836.1:g.4160T>C and NG_012836.1:g.4326G>A on protein expression levels in vitro and identified the functional sequence in the regulatory region of the GABRB3 gene linked to possible associations with schizophrenia. METHODS: Recombinant plasmids with haplotypes T-G and C-A and 10 recombinant vectors containing deletion fragments from the GABRB3 gene 5' regulatory region were transfected into HEK-293, SK-N-SH, and SH-SY5Y cells. The relative fluorescence intensity of the two haplotypes and different sequences was compared using a dual luciferase reporter assay system. RESULTS: The relative fluorescence intensity of haplotype C-A was significantly lower than that of T-G. We shortened the core promoter sequence of the GABRB3 gene 5' regulation region from -177 bp to -18 bp (ATG+1). We also found an expression suppression region from -1,735 bp to -1,638 bp and an enhanced regulatory region from -1,638 bp to -1,335 bp. Multiple inhibitory functional elements were identified in the region from -680 bp to -177 bp. CONCLUSION: We demonstrated that haplotype C-A might increase the risk of schizophrenia and found multiple regulatory regions that had an effect on GABRB3 receptor expression.


Assuntos
Receptores de GABA-A/genética , Esquizofrenia/genética , Região 5'-Flanqueadora , Linhagem Celular Tumoral , Células HEK293 , Haplótipos , Humanos , Regiões Promotoras Genéticas , Receptores de GABA-A/metabolismo
8.
BMC Med Genet ; 20(1): 26, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30704411

RESUMO

BACKGROUND: Schizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. Abnormal glutamate ionotropic N-methyl-D-aspartate receptor (NMDA) type subunit 1 (NR1) may be a potential cause of schizophrenia. METHODS: We conducted a case-control study to investigate the association between the GRIN1 gene, which encodes the NR1 subunit, and the risk of schizophrenia in a northern Chinese Han population using Sanger DNA sequencing. The dual luciferase reporter assay was used to detect the influence of two different haplotypes on GRIN1 gene expression. RESULTS: Seven SNPs (single nucleotide polymorphisms), including rs112421622 (- 2019 T/C), rs138961287 (- 1962--1961insT), rs117783907 (-1945G/T), rs181682830 (-1934G/A), rs7032504 (-1742C/T), rs144123109 (-1140G/A), and rs11146020 (-855G/C) were detected in the study population. Rs117783907 (-1945G/T) was associated with the occurrence of schizophrenia as a protective factor. The genotype frequencies of rs138961287 (- 1962--1961insT) and rs11146020 (-855G/C) were statistically different between cases and controls (p < 0.0083). The other four variations were not shown to be associated with the disease. Two haplotypes were composed of the seven SNPs, and distribution of T-del-G-G-C-G-G was significantly different between the case and control groups. However, the dual luciferase reporter assay showed that neither of the haplotypes affected luciferase expression in HEK-293 and SK-N-SH cell lines. CONCLUSIONS: The GRIN1 gene may be related to the occurrence of schizophrenia. Additional research will be needed to fully ascertain the role of GRIN1 in the etiology of schizophrenia.


Assuntos
Grupo com Ancestrais do Continente Asiático/etnologia , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Receptores de N-Metil-D-Aspartato/genética , Esquizofrenia/genética , Análise de Sequência de DNA/métodos , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Células HEK293 , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Elementos Reguladores de Transcrição , Esquizofrenia/etnologia
9.
Electrophoresis ; 40(11): 1591-1599, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30740746

RESUMO

Semi-nested PCR with allele-specific (AS) primers and sequencing of mitochondrial DNA (mtDNA) were performed to analyze and interpret DNA mixtures, especially when biological materials were degraded or contained a limited amount of DNA. SNP-STR markers were available to identify the minor DNA component using AS-PCR; moreover, SNPs in mtDNA could be used when the degraded or limited amounts of DNA mixtures were not successful with SNP-STR markers. Five pairs of allele-specific primers were designed based on three SNPs (G15043A, T16362C, and T16519C). The sequence of mtDNA control region of minor components was obtained using AS-PCR and sequencing. Sequences of the amplification fragments were aligned and compared with the sequences of known suspects or databases. When this assay was used with the T16362C and T16519C SNPs, we found it to be highly sensitive for detecting small amounts of DNA (∼30 pg) and analyzing DNA mixtures of two contributors, even at an approximately 1‰ ratio of minor and major components. An exception was tests based on the SNP G15043A, which required approximately 300 pg of a 1% DNA mixture. In simulated three contributor DNA mixtures (at rate of 1:1:1), control region fragments from each contributor were detected and interpreted. AS-PCR combined with semi-nested PCR was successfully used to identify the mtDNA control region of each contributor, providing biological evidence for excluding suspects in forensic cases, especially when biological materials were degraded or had a limited amount of DNA.

10.
Front Mol Neurosci ; 12: 13, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30766477

RESUMO

Abnormal expression of the 5-HT1A receptor, which is encoded by the HTR1A gene, leads to susceptibilities to neuropsychiatric disorders such as depression, anxiety, and schizophrenia. miRNAs regulate gene expression by recognizing the 3'-UTR region of mRNA. This study evaluated the miRNAs that might identify and subsequently determine the regulatory mechanism of HTR1A gene. Using the HEK-293, U87, SK-N-SH and SH-SY5Y cell lines, we determined the functional sequence of the 3'-UTR region of the HTR1A gene and predicted miRNA binding. Dual luciferase reporter assay and Western Blot were used to confirm the effect of miRNA mimics and inhibitors on endogenous 5-HT1A receptors. In all cell lines, gene expression of the -17 bp to +443 bp fragment containing the complete sequence of the 3'-UTR region was significantly decreased, although mRNA quantification was not different. The +375 bp to +443 bp sequence, which exhibited the most significant change in relative chemiluminescence intensity, was recognized by hsa-miR-3177-5p and hsa-miR-3178. In HEK-293 and U87 cells, hsa-miR-3177-5p significantly inhibited the 5-HT1A receptor expression, while a hsa-miR-3178 inhibitor up-regulated HTR1A gene expression in SK-N-SH and SH-SY5Y cells. By constructing the pmirGLO-vector with the mutated HTR1A gene, we further confirmed that hsa-miR-3177-5p recognized the HTR1A gene tgtacaca at +377 bp to +384 bp, and the +392 bp to +399 bp fragment cgcgccca was identified by hsa-miR-3178. hsa-miR-3177-5p and hsa-miR-3178 had significant inhibitory effects on expression of the HTR1A gene and 5-HT1A receptor and may directly participate in the development of neuropsychiatric diseases.

11.
Brain Behav ; 9(2): e01193, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30657260

RESUMO

BACKGROUND: Epidemiological studies found that genetic factors are among the causes of schizophrenia, exclusively the genes involved in the dopamine system. Prior to this, the role of dopamine receptor D2 (DRD2) gene promoter polymorphisms and schizophrenia has been studied extensively, but there are still some uncertainties about these associations. The present study is focusing on the association between the DRD2 gene promoter region polymorphisms and schizophrenia in the northern Chinese Han population. METHODS: We sequenced 2,111-bp fragment of DRD2 gene promoter region in 306 schizophrenic patients and 324 healthy controls to find association between DRD2 and schizophrenia. SPSS version 18 0.0 was used to calculate odds ratios (OR), 95% confidence intervals (CIs).The Hardy-Weinberg equilibrium test and the confirmation of haplotypes were calculated using Haploview version 4.1. The association of schizophrenic risk of DRD2 genotypes, alleles, and haplotypes between case and control groups was calculated using the chi-squared test. PS program was used to calculate the Power analysis. RESULTS: The genotype frequencies of rs7116768 (p = 0.025) and rs1799732 (p = 0.042) were associated meagerly. After Bonferroni correction, there was no association found between DRD2 gene promoter region with schizophrenia risk in the northern Chinese Han population. CONCLUSIONS: In this study, we did not find any significant difference between schizophrenia and the polymorphisms of DRD2 gene promoter region. A more forceful conclusion remains to be verified by further confirmatory experiments.


Assuntos
Receptores de Dopamina D2/genética , Esquizofrenia , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Correlação de Dados , Dopamina/metabolismo , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Polimorfismo Genético , Regiões Promotoras Genéticas , Esquizofrenia/epidemiologia , Esquizofrenia/genética
12.
Neuropsychiatr Dis Treat ; 15: 143-155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30643413

RESUMO

Background: In order to explore the association between the SLC6A4 gene and the risk of schizophrenia, an updated meta-analysis was conducted using a total of 46 scientific articles. Methods: Through a literature search, papers studied included 35 articles on serotonin-transporter-linked polymorphic region (5-HTTLPR) with 8,752 cases and 10,610 controls, 17 articles on second intron variable number of tandem repeats with 7,284 cases and 8,544 controls, four studies on rs1042173 with 1,351 cases and 2,101 controls, and four studies on rs140700 with 1,770 cases and 2,386 controls. Pooled, subgroup, and sensitivity analyses were performed, and the results were visualized by forest and funnel plots. Results: An association between 5-HTTLPR and the risk of schizophrenia was not found, except for an Indian subgroup analysis (Pz =0.014, OR =1.749, 95% CI =1.120-2.731). A 10 repeats/12 repeats (10R/12R) genotype was a protective factor against schizophrenia (Pz =0.020, OR =0.789, 95% CI =0.646-0.963), but a 12R/12R genotype was a risk factor for schizophrenia (Pz =0.004, OR =1.936, 95% CI =1.238-3.029) in the pooled analyses. In Caucasians, a GG genotype of rs1042173 may be a risk factor for schizophrenia (Pz =0.006, OR =1.299, 95% CI =1.079-1.565). No association was found between rs140700 and the risk for schizophrenia. Conclusion: Through meta-analysis, we were able to gain insight into previously reported associations between SLC6A4 polymorphism and schizophrenia.

13.
Ann Hum Genet ; 83(3): 134-140, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30506867

RESUMO

BACKGROUND: China harbors 56 ethnic groups, including Korean, with a population size of approximately 1.92 million at the 2010 census. Most of the Koreans live in Northeastern parts of China, including Jilin (59.64%), Heilongjiang (20.21%), and Liaoning (12.55%) provinces, and the rest are spread to other parts of China. Koreans across China share a common culture, which is similar to Korea. METHODS: We have explored the genetic characteristics of 20 Y-chromosomal short tandem repeat (Y-STR) loci in 252 unrelated Chinese Korean male individuals from Jilin Province, using a Goldeneye 20Y amplification kit. Moreover, phylogenetic analysis was performed between the Korean population and other relevant populations based on the Y-STR haplotypes. RESULTS: We have found 237 different haplotypes among 252 unrelated individuals. The haplotype frequencies ranged from 0.0238 to 0.0040, while gene diversity ranged from 0.9666 (DYS385a/b) to 0.2260 (DYS391). The random match probability was 0.0048, the haplotype diversity was 0.9992 ± 0.0006 and discrimination capacity was 0.9405. Population comparison revealed that Korean populations are lining up together with other Korean populations from East Asia. CONCLUSION: Our results showed that the 20 Y-STR loci in the Yanbian Korean population are valuable for forensic application and human genetics. The Yanbian Koreans have lined up with other Korean population from China and Korea while showing significant differences from other East Asian populations.


Assuntos
Cromossomos Humanos Y/genética , Grupos Étnicos/genética , Genética Populacional , Grupo com Ancestrais do Continente Asiático/genética , China , Frequência do Gene , Haplótipos , Humanos , Masculino , Filogenia , República da Coreia/etnologia
15.
BMC Genet ; 19(1): 115, 2018 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-30594152

RESUMO

BACKGROUND: The serotonin neurotransmitter (5-HT) and its receptors have important roles in neuropsychiatric disorders such as schizophrenia. The aim of this study was to investigate the functional sequences of the 5' regulation region of the human HTR1A gene to explore the effects on the expression of the 5-HT1A receptor. METHODS: Fourteen recombinant pGL3-basic vectors containing deletion fragments of the HTR1A gene regulatory region were transfected with HEK-293 and SK-N-SH cells. The relative chemiluminescence intensities of different length fragments were analyzed. The JASPAR software was used for the prediction of transcription factors. RESULTS: In the HEK-293 cells, the relative chemiluminescence intensity of the - 1649 bp to - 1550 bp (ATG + 1) fragment was significantly different. Two inhibitory activity regions were found in the - 1409 bp to - 1381 bp and - 1196 bp to - 1124 bp fragments, which might be bound to the GATA or SOX10 transcription factors as predicted by the JASPAR software. In addition, the fragments located from - 1124 bp to - 1064 bp and from - 908 bp to - 722 bp up-regulated protein expression. Only the sequence from - 1550 bp to - 1409 bp demonstrated a difference in luciferase expression in the both cell lines. According to the results of the 5'-UTR truncated vectors, there was a repression region at the distal end of the 5'-UTR, an enhancer region might be present at the proximal end of the transcription start site. CONCLUSIONS: Although the functional sequences of the HTR1A gene regulatory region were confirmed, the regulatory factors and functional components require further investigation.


Assuntos
Receptor 5-HT1A de Serotonina/genética , Regiões 5' não Traduzidas , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Genes Reporter , Células HEK293 , Humanos , Receptor 5-HT1A de Serotonina/metabolismo , Elementos Reguladores de Transcrição , Esquizofrenia/genética , Esquizofrenia/patologia , Deleção de Sequência , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Transfecção
16.
BMC Psychiatry ; 18(1): 303, 2018 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-30231895

RESUMO

BACKGROUND: Schizophrenia is associated with multiple neurotransmitter disorders, including serotonin (5-hydroxytryptamine, 5-HT). The neuromodulatory action of serotonin on brain function largely depends on the action of specific subtypes of serotonin receptors. The serotonin receptor 1B (HTR1B) gene has been proposed to play putative roles in the development of multiple emotional and psychiatric disorders. METHODS: To study the relationship of HTR1B polymorphisms and schizophrenia, gene information was drawn from a cohort of 310 schizophrenic patients (152 men and 158 women) and 313 healthy controls (153 men and 160 women) of northern Han Chinese descent. The χ2 test was used to compare allele and genotype distributions between case and control groups. The haplotype and linkage equilibrium were also assessed in two group comparisons. RESULTS: We detected 14 SNPs. Male patients were observed to have higher frequencies of the A-allele and AA+AG genotype at rs1778258 than female patients (p = 0.012 and p = 0.015, respectively). Both the A-allele and AA+AG genotype were associated with schizophrenia risk (OR = 1.986 and OR = 2.061, respectively), although the statistical significance of the genotype was lost after Bonferroni correction. Linkage analysis showed that rs17273700, rs11568817, rs9361234 and rs58138557 polymorphisms exhibit strong linkage disequilibrium (LD). In addition, schizophrenic patients show stronger linkage between 11,568,817 and rs130058 than healthy controls. CONCLUSIONS: HTR1B polymorphisms are associated with schizophrenia in the northern Han Chinese population, which provides an etiological reference for schizophrenia.


Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptor 5-HT1B de Serotonina/genética , Esquizofrenia/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Feminino , Marcadores Genéticos , Genótipo , Haplótipos , Humanos , Masculino
17.
J Mol Neurosci ; 65(4): 438-443, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30022436

RESUMO

Dysregulation of dopamine receptor D1 (DRD1) is involved in multiple neuropsychiatric disorders. The 5' regulatory region of DRD1 has not been characterized fully. We applied the luciferase assay and the electrophoretic mobility shift assay to explore the activity of the 5' regulatory region of DRD1 in SH-SY5Y and 293T cells. We found that the promoter region of DRD1 corresponded to positions - 1250 to + 250 in the DNA sequence, and the putative core promoter region was from - 113 to + 250 (transcriptional start site of exon, +1). The sequence 5'-gggacgcgcgggcggggtgggctgtgccccgcgggaaccccgccggcctgtgcgcttgctg-3' was identified as a possible transcription factor-binding domain. Further research is warranted to explore the function of the 5' regulatory region of DRD1.


Assuntos
Regiões Promotoras Genéticas , Receptores de Dopamina D1/genética , Linhagem Celular Tumoral , Células HEK293 , Humanos , Motivos de Nucleotídeos , Ligação Proteica , Receptores de Dopamina D1/metabolismo , Fatores de Transcrição
18.
J Neurol Sci ; 385: 192-197, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29406904

RESUMO

OBJECTIVE: To observe and compare the efficacy and tolerability of azathioprine (AZA), mycophenolate mofetil (MMF) and lower dosages of rituximab (RTX) among patients with neuromyelitis optica spectrum disorder. METHODS: In this prospective cohort, AQP4-IgG-seropositive patients with neuromyelitis optica spectrum disorder (NMOSD) were enrolled and randomly divided into three groups, using AZA, MMF or lower dosages of RTX (defined as 100mg RTX intravenous injection, once per week for 4 consecutive weeks) respectively. Annualized relapse rate (ARR), EDSS scores, CD19+ B-cell counts in peripheral blood, serum AQP-4-IgG titre and drug adverse reactions were compared between three groups. RESULTS: In the AZA group (n=22), MMF group (n=30) and RTX group (n=20), 54.5%, 60.0% and 65.0% of patients reached a relapse-free state and EDSS score improved in 90.9%, 83.3% and 90.0% of patients respectively. In addition, there was significant reduction in ARR in all the three groups. Reduced dosage of RTX exerted a significant effect in reducing CD19+ B-cell counts (P<0.01). Compared with the AZA group, the MMF group and the RTX group decreased the AQP-4-IgG titre evidently and caused fewer adverse events. Neither the Kaplan-Meier survival curves nor the Cox proportional hazard model indicated a significant difference in relapse among the three groups (P>0.05). CONCLUSIONS: AZA, MMF and reduced dosages of rituximab are all effective in reducing ARR and improving the clinical symptom of patients with NMOSD. Lower dosages of RTX are more effective than the others in decreasing the CD19 B-cell counts. MMF and reduced RTX decrease AQP-4-IgG titre more and cause fewer adverse events than AZA. However, more multicentre studies are still needed to find more effective therapeutic regimen.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Adulto , Aquaporina 4/imunologia , Azatioprina/uso terapêutico , Linfócitos B/metabolismo , Linfócitos B/patologia , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Neuromielite Óptica/imunologia , Rituximab/uso terapêutico , Resultado do Tratamento
19.
Fish Shellfish Immunol ; 76: 27-34, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29444463

RESUMO

White shrimp Litopenaeus vannamei were reared under conditions of gradual changes to a low pH (gradual-low pH, 6.65-8.20) or a high pH (gradual-high pH, 8.20-9.81) versus a normal pH environment (8.14-8.31) during a 28-day period. Survival of shrimp, and ROS production, antioxidant responses and oxidative damage in the hepatopancreas and midgut were investigated. Consequently, shrimp enhanced MnSOD, GPx, and Hsp70 transcripts as early defense mechanism in the hepatopancreas and midgut to scavenge excessive ROS during short-term (≤ 7 days) gradual-low and high pH stress. Meanwhile, the hepatopancreas was more sensitive to ROS than midgut because of earlier ROS production increase, antioxidant response and oxidative damage. Then, suppressed antioxidant response in the hepatopancreas and midgut of shrimp suggested a loss of antioxidant regulatory capacity caused by aggravated oxidative damage after long-term (≥ 14 days) gradual-high pH stress, leading to continuous death. However, enhanced GPx, GST, and Hsp70 transcripts in the hepatopancreas and midgut might be long-term(≥ 14 days) antioxidant adaptation mechanism of shrimp to gradual-low pH stress, which could prevent further ROS perturbation and weaken oxidative damage to achieve a new immune homeostasis, contributing to stable survival rate. Therefore, we have a few insights that it is necessary to protect hepatopancreas for controlling shrimp death under gradual-high pH stress.


Assuntos
Proteínas de Artrópodes/metabolismo , Imunidade Inata , Estresse Oxidativo/fisiologia , Penaeidae/enzimologia , Água/química , Animais , Hepatopâncreas/metabolismo , Concentração de Íons de Hidrogênio , Mucosa Intestinal/metabolismo
20.
Neuropsychiatr Dis Treat ; 14: 153-164, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29379288

RESUMO

To explore the association between DRD4 polymorphisms and schizophrenia risk, a meta-analysis was carried out with 41 case-control articles. Specifically, we included 28 articles (5,735 cases and 5,278 controls) that pertained to the 48 bp variable number tandem repeat (VNTR) polymorphism, nine articles (1,517 cases and 1,746 controls) that corresponded to the 12 bp tandem repeat (TR), six articles (1,912 cases and 1,836 controls) that addressed the 120 bp TR, 10 articles (2,927 cases and 2,938 controls) that entailed the -521 C>T polymorphism, six articles (1,735 cases and 1,724 controls) that pertained to the -616 C>G polymorphism, and four articles (1,191 cases and 1,215 controls) that involved the -376 C>T polymorphism. Pooled analysis, subgroup analysis, and sensitivity analysis were performed, and the data were visualized by means of forest and funnel plots. Results of pooled analysis indicated that the -521 CC variant (Pz=0.009, odds ratio [OR] =1.218, 95% confidence interval [CI] =1.050-1.413) and genotype L/L (ie, long allele) of the 120 bp TR were risk factors of schizophrenia (Pz=0.004, OR =1.275, 95% CI =1.081-1.504). The 48 bp VNTR, the 12 bp TR, the -616 C>G polymorphism, and the -376 C>T polymorphism were not associated with schizophrenia. Additional research is warranted to explore the association between polymorphisms of DRD4 and schizophrenia risk.

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