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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 5-7, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922585

RESUMO

OBJECTIVE: To analyze variants of PRRT2 gene in two children with paroxysmal kinesigenic dyskinesia. METHODS: Genomic DNA of the two children and their parents was extracted from peripheral venous blood samples. All exons and their flanking regions of the PRRT2 gene were subjected to PCR and Sanger sequencing. RESULTS: The two children were found to respectively harbor a c.282dupA and a c.715_716dupCC variant in exon 2 of the PRRT2 gene, which were both inherited from their mothers. Pooling together their frequencies in general population, genetic models, related literature and impact on protein function, the two novel variants were both predicted to be pathogenic. CONCLUSION: The c.282dupA and c.715_716dupCC variants probably underlie the disease in the two children.


Assuntos
Distonia , Proteínas de Membrana , Proteínas do Tecido Nervoso , Criança , Distonia/genética , Feminino , Humanos , Proteínas de Membrana/genética , Mutação , Proteínas do Tecido Nervoso/genética
2.
Biosci Biotechnol Biochem ; 84(1): 154-158, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794328

RESUMO

Malectin is a maltose-binding endoplasmic reticulum protein conserved in animals. In Arabidopsis thaliana, we identified four genes that encode malectin-like domain (MLD)- and leucine-rich repeat (LRR)-containing proteins (AtMLLRs): two were receptor-like proteins (AtMLLR1 and 2) and the other two were extracellular proteins (AtMLLR3 and 4). The promoter:G3GFP+promoter:GUS assay indicated the organ- and cell-specific expression of the AtMLLR2 and AtMLLR3 genes.Abbreviations: Cmr: chloramphenicol-resistance marker; G3GFP: G3 green fluorescent protein; GUS: ß-glucuronidase; KD: kinase domain; LRR: leucine-rich repeat; MLD: malectin-like domain; RLK: receptor-like kinase; SP: signal peptide; TMD: transmembrane domain; Tnos: nopaline synthase terminator.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Expressão Gênica , Lectinas/genética , Proteínas de Membrana/genética , Proteínas/genética , Retículo Endoplasmático/metabolismo , Glucuronidase/química , Proteínas de Fluorescência Verde/química , Leucina/genética , Microscopia de Fluorescência , Filogenia , Plantas Geneticamente Modificadas , Domínios Proteicos/genética , Coloração e Rotulagem
3.
Yi Chuan ; 41(12): 1110-1118, 2019 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-31857282

RESUMO

Myogenesis is a complex physiological process that is mainly involved in the proliferation of myogenic stem cells to form myoblasts, which then differentiated and fused to form multinucleated myotubes. Many proteins have been found to be involved in myoblast fusion, but none of them are muscle-specific fusion proteins. In recent years, two muscle-specific transmembrane proteins, i.e. Myomaker and Myomerger, have been discovered and identified, which can coordinate and promote the fusion of myoblasts and thus participate in the process of myogenesis. In this review, we summarize the research progress of Myomaker and Myomerger in myogenesis, including their expression patterns and functional domains, as well as their participation in myoblast fusion mechanisms, aiming to provide relevant ideas for in-depth study of the myogenesis process and treatment of diseases related to myoblast fusion.


Assuntos
Proteínas de Membrana , Músculo Esquelético , Mioblastos , Animais , Diferenciação Celular , Fusão Celular , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Desenvolvimento Muscular , Proteínas Musculares , Músculo Esquelético/citologia , Mioblastos/citologia
4.
Anticancer Res ; 39(11): 6379-6387, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704871

RESUMO

BACKGROUND/AIM: In the present retrospective study, we assessed the molecular profile and clinicopathological correlations of Greek colorectal carcinoma (CRC) patients. PATIENTS AND METHODS: Data from 157 CRC patients were collected. High Resolution Melting Analysis and Pyrosequencing/Sanger sequencing were applied to identify KRAS, BRAF, NRAS mutations and microsatellite instability (MSI) status. Immunohistochemistry was performed to characterize the associated Mismatch Repair Protein loss. Statistical calculations were performed using the statistical package SPSS v21.0. RESULTS: KRAS mutations were detected in 39.3% of cases, BRAF in 10.9% and NRAS in 4.9%. MSI status was recognized in 11.5% of CRC patients and was associated with right colon tumors. MSI phenotype was inversely correlated with stage, N status and KRAS mutations and positively correlated with BRAF mutations. CONCLUSION: MSI positive CRCs in the Greek population are more often right-sided, free of metastasis, KRAS wild type and BRAF mutated. Providing more detailed clinicopathological and molecular data for specific populations will enable better clinical management and individualized therapy in the future.


Assuntos
Neoplasias do Colo/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Instabilidade de Microssatélites , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Feminino , Grécia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Neoplasias do Colo Sigmoide/genética , Neoplasias do Colo Sigmoide/patologia
5.
Bratisl Lek Listy ; 120(11): 832-838, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31747763

RESUMO

Head and neck squamous cell carcinomas (HNSCC) are a highly heterogenous disease which can be induced by two main carcinogens - tobacco and/or alcohol, or by HR HPV infection. This work examined 60 paraffin-embedded biopsies of head and neck carcinomas after histological verification. HPV infection, including its specific types in various HNSCC areas, was studied using multiplex qPCR. Expression levels of p16INK4A and p53 were detected by subsequent IHC analysis as being potential diagnostic markers. Based on the assumption that patients with HNSCC could benefit from anti-EGFR therapy (cetuximab), but the predictors are not yet defined, analyses of point mutations of ras genes (Kras, Nras) were carried out using multiplex qPCR and sequence analysis of the Braf gene. All statistical data were processed by Chí-x2 test.HPV infection was detected in 23.34 % of cases with HNSCC, of which 100 % were HPV 16, which is the most frequently infection found in the oropharyngeal region. Using IHC analysis, a positive expression of P16INK4A was detected in 100 % of HPV-positive HNSCC while this expression was discovered to be highly correlated with HPV infection. Furthermore, a correlation between p53 and HPV-negative HNSCC was proved. The mutation incidence was the highest in the Kras gene (codon 12 and codon 146), Nras (codon 12) and Braf. A correlation between tumor location in the oropharyngeal region and Kras mutations was proved. The HPV infection correlated with Kras mutations in case of codon 146 but on the grounds of low amount of output data, these figures could be irrelevant. In one case, c.1808 G>A, protein 603 Arg>Gln mutation was found in the Braf gene but its correlation with head and neck carcinomas has not been described yet (Tab. 2, Fig. 2, Ref. 24). Keywords: head and neck carcinomas, biopsy, HPV types, PCR, p16INK4A, p53, molecular predictors, Kras, Nras, Braf.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , GTP Fosfo-Hidrolases/genética , Neoplasias de Cabeça e Pescoço/virologia , Papillomavirus Humano 16 , Humanos , Imuno-Histoquímica , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética
6.
Medicine (Baltimore) ; 98(44): e17821, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689868

RESUMO

Although many genetic variants related to anti-tuberculosis drug induced liver injury (ATDILI) have been identified, the prediction and personalized treatment of ATDILI have failed to achieve, indicating there remains an area for further exploration. This study aimed to explore the influence of single nucleotide polymorphisms (SNPs) in Bradykinin receptor B2 (BDKRB2), Teneurin transmembrane protein 2 (TENM2), transforming growth factor beta 2 (TGFB2), and solute carrier family 2 member 13 (SLC2A13) on the risk of ATDILI.The subjects comprised 746 Chinese tuberculosis (TB) patients. Custom-by-design 2x48-Plex SNPscanTM kit was employed to genotype 28 selected SNPs. The associations of SNPs with ATDILI risk and clinical phenotypes were analyzed according to the distributions of allelic and genotypic frequencies and different genetic models. The odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated.Among subjects with successfully genotyped, 107 participants suffered from ATDILI during follow-up. In BDKRB2, patients with rs79280755 G allele or rs117806152 C allele were more vulnerable to ATDILI (PBonferronicorrection = .002 and .03, respectively). Rs79280755 increased the risk of ATDILI significantly whether in additive (OR = 3.218, 95% CI: 1.686-6.139, PBonferroni correction = .003) or dominant model (PBonferroni correction = .003), as well as rs117806152 (Additive model: PBonferroni correction = .05; dominant model: PBonferroni correction = .03). For TENM2, rs80003210 G allele contributed to the decreased risk of ATDILI (PBonferroni correction = .02), while rs2617972 A allele conferred susceptibility to ATDILI (PBonferroni correction = .01). Regarding rs2617972, significant findings were also observed in both additive (OR = 3.203, 95% CI: 1.487-6.896, PBonferroni correction = .02) and dominant model (PBonferroni correction = .02). Moreover, rs79280755 and rs117806152 in BDKRB2 significantly affected some laboratory indicators. However, no meaningful SNPs were observed in TGFB2 and SLC2A13.Our study revealed that both BDKRB2 and TENM2 genetic polymorphisms were interrogated in relation to ATDILI susceptibility and some laboratory indicators in the Western Chinese Han population, shedding a new light on exploring novel biomarkers and targets for ATDILI.


Assuntos
Antituberculosos/efeitos adversos , Sinalização do Cálcio/genética , Doença Hepática Induzida por Substâncias e Drogas/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Receptor B2 da Bradicinina/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Proteínas Facilitadoras de Transporte de Glucose/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fator de Crescimento Transformador beta2/genética
7.
Protein Pept Lett ; 26(10): 751-757, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618170

RESUMO

BACKGROUND: NMAAP1 plays a role in regulating macrophage differentiation to the M1 type and exerting antitumoral functions. It is not clear what role and mechanism NMAAP1 does play in the reversal of macrophages from M1 to M2. METHODS: We detected the typing of macrophages with high or low expression of NMAAP1 by QPCR and ELISA, and detected the colocalization of NMAAP1 and endogenous IP3R by laser confocal microscopy, and detected the protein expression in cells by Western-blotting. RESULTS: Our study found that knockdown NMAAP1 in RAW264.7 cells induced macrophage polarization to the M2 type and up-regulation of NMAAP1 in RAW264.7 cells maintain M1 Phenotype even in the presence of IL-4, a stronger inducer of the M2 type. Additionally, Coimmunoprecipitation revealed a protein-protein interaction between NMAAP1 and IP3R and then activates key molecules in the PKC-dependent Raf/MEK/ERK and Ca2+/CaM/CaMKII signaling pathways. Activation of PKC (Thr638/641), ERK1/2 (Thr202/Tyr204) and CaMKII (Thr286) is involved in the regulation of cell differentiation. CONCLUSION: NMAAP1 interacts with IP3R, which in turn activates the PKC-dependent Raf/MEK/ERK and Ca2+/CaM/CaMKII signaling pathways. These results provide a new explanation of the mechanism underlying M1 differentiation.


Assuntos
Cálcio/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Macrófagos/metabolismo , Proteínas de Membrana/metabolismo , Transdução de Sinais , Animais , Diferenciação Celular , Citocinas/metabolismo , Regulação da Expressão Gênica , Humanos , Macrófagos/citologia , Proteínas de Membrana/genética , Camundongos , Fenótipo , Ligação Proteica , Células RAW 264.7 , RNA Interferente Pequeno/metabolismo , Regulação para Cima
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 1022-1024, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598951

RESUMO

OBJECTIVE: To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF). METHODS: Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The fetus was found to carry compound heterozygous variants c.1440+1G>A and c.925G>T of the NPHS1 gene, which were respectively inherited from its mother and father. CONCLUSION: Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.


Assuntos
Síndrome Nefrótica/congênito , Síndrome Nefrótica/diagnóstico , Feminino , Feto , Finlândia , Heterozigoto , Humanos , Proteínas de Membrana/genética , Gravidez , Diagnóstico Pré-Natal
9.
DNA Cell Biol ; 38(11): 1188-1196, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31603699

RESUMO

The mammary gland is an important organ for lactation in dairy goats. Mammary gland development and lactation functions are primarily regulated by natural hormones and certain crucial regulatory factors. Nedd4 family-interacting protein 1 (Ndfip1) can specifically bind to neural precursor cell-expressed, developmentally downregulated protein 4 (Nedd4) family members to participate in ubiquitination, which in turn regulates a range of biological processes in the body. However, the effects of Ndfip1 expression regulation at the post-transcriptional level on the development of mammary gland cells have not been previously reported. To study the regulation of Ndfip1 at post-transcriptional level, the overexpression and interference vectors of Ndfip1 were constructed, and co-transfected into the primary mammary gland epithelial cells cultured in vitro with miR-143 mimics and inhibitor. Dual luciferase reporter gene system, real-time quantitative polymerase chain reaction, western blotting, cholecystokinin octapeptide assays, and flow cytometry were used to identify their regulation and function. As a result, Ndfip1 was targeted and regulated by miR-143, which influences the development of mammary gland epithelial cells in dairy goats cultured in vitro. This study will lay an experimental foundation for further understanding the functions of Ndfip1 and miR-143.


Assuntos
Apoptose/genética , Células Epiteliais/fisiologia , Cabras , Lactação/genética , Glândulas Mamárias Animais/fisiologia , Proteínas de Membrana/genética , MicroRNAs/fisiologia , Animais , Células Cultivadas , Indústria de Laticínios , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Cabras/genética , Cabras/metabolismo , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/metabolismo
10.
Life Sci ; 237: 116902, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610195

RESUMO

AIMS: Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) promotes hepatic stellate cell (HSC) autophagy and activation. However, the underlying mechanism remains unknown. Noncoding RNAs (ncRNAs) including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), have received increasing attention. We aimed to investigate the roles of the lncRNA nuclear enriched abundant transcript 1 (NEAT1), miR-29b, and autophagy related protein 9a (Atg9a), and their relationships with each other during IGFBPrP1-induced HSC autophagy and activation. MAIN METHODS: Levels of NEAT1, miR-29b, Atg9a, and autophagy were detected in adenovirus-mediated IGFBPrP1 (AdIGFBPrP1)-treated mouse liver tissue and immortalized mouse hepatic stellate cell line JS1 transfected with either AdIGFBPrP1 or siIGFBPrP1. In AdIGFBPrP1-treated JS1 cells, autophagy and activation were detected after altering NEAT1, miR-29b, or Atg9a levels. In AdIGFBPrP1-treated JS1 cells, relationships among NEAT1, miR-29b, and Atg9a were explored using dual-luciferase reporter assays, Western blot, qRT-PCR, and immunofluorescence. KEY FINDINGS: IGFBPrP1 increased levels of NEAT1, Atg9a, and autophagy while decreasing the level of miR-29b in mouse liver tissues and mouse HSCs. Moreover, NEAT1 increased HSC autophagy and activation while miR-29b decreased both processes. Atg9a also participated in IGFBPrP1-induced HSC autophagy and activation. Importantly, NEAT1, miR-29b, and Atg9a formed a NEAT1/miR-29b/Atg9a regulatory axis for IGFBPrP1-induced HSC autophagy and activation. SIGNIFICANCE: Our study unveiled the new NEAT1/miR-29b/Atg9a regulatory axis involved in IGFBPrP1-induced mouse HSC autophagy and activation. The study thus provides new insights in the pathogenesis and potential therapeutic strategies of liver fibrosis.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Autofagia , Células Estreladas do Fígado/patologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Cirrose Hepática/patologia , Proteínas de Membrana/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteínas de Transporte Vesicular/metabolismo , Adenoviridae/genética , Animais , Proteínas Relacionadas à Autofagia/genética , Células Cultivadas , Células Estreladas do Fígado/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Transporte Vesicular/genética
11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 373-378, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31631606

RESUMO

Objective: To establish a radiomic model for predicting lymph node (LN) metastasis in patients with non-small cell lung cancer (NSCLC). Methods: The prediction model was developed using a training cohort comprising 100 patients with clinicopathologically confirmed NSCLC. Data were gathered from January 2014 to December 2015. Radiomic features of NSCLC were obtained from non-contrast and enhancement computed tomography (CT). Lasso-logistic regression models were established for data dimension reduction, feature selection, and radiomics signature building. Consistency coefficient ( ICCs) was used to evaluate the consistency between observer interior and interobserver.The consistency index (C-index)is used to evalutate the prediction of lymph node metastasis by using the radiomics signature, shown with the area under the receiver operating characteristic curve ( AUC).Multivariate logistic regression analyses were performed to develop the prediction model, considering radiomics signature and clinicopathologic risk factors. The radiomics model was validated in a validation cohort comprising 100 consecutive NSCLC patients from January 2016 to December 2017 in terms of its calibration and discrimination. AUC was used to evaluate the predictive effectiveness of the model, and Delong test was used to compare models. Hosmer-Lemeshow good of fit test was used to evaluate the calibration of prediction models.The results were represented by correction curves to compare the consistency between the predicted results of the model and the actual probability of LN metastasis. Results: The consistency between observer interior and interobserver was good, with ICCs higher than 0.75.The radiomics signature, including 22 selected features, was associated with LN metastasis. AUC was 0.781 in training cohort and 0.776 in validation cohort. The individualized prediction model identified radiomics signature, neuron specific enolase (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and carbohydrate antigen 125 (CA125) as independent predictors. The model showed good discrimination, with 0.836 AUC in the training cohort, and 0.821 AUC in the validation cohort. The model in both the training and validation cohorts had good calibration,which demonstrated high consistency with the actual LN metastasis. Conclusion: The radiomics model incorporating radiomics signature and clinical risk factors can be conveniently used to facilitate preoperative individualized prediction of LN metastasis in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Metástase Linfática/diagnóstico , Antígenos de Neoplasias/genética , Antígeno Ca-125/genética , Humanos , Queratina-19/genética , Modelos Logísticos , Linfonodos , Proteínas de Membrana/genética , Fosfopiruvato Hidratase/genética , Valor Preditivo dos Testes , Estudos Retrospectivos
12.
Zhonghua Yi Xue Za Zhi ; 99(36): 2831-2835, 2019 Sep 24.
Artigo em Chinês | MEDLINE | ID: mdl-31550811

RESUMO

Objective: To investigate the expression of Golgi phosphoprotein 3 (GOLPH3) in papillary thyroid carcinoma (PTC) and its relationship with clinicopathological characteristics of PTC and American Thyroid Association (ATA) risk of recurrence stratification. Methods: The mRNA expression level of GOLPH3 in PTC tissues and the matched adjacent noncancerous tissues from 30 cases of PTC undergoing surgical operation in Fujian Provincial Hospital between March 2017 and April 2018 was detected by reverse transcription-quantitative PCR (RT-qPCR). The protein expression of GOLPH3 in PTC tissues and the matched adjacent noncancerous tissues of 135 cases of PTC between January 2013 and April 2018 was measured by immunohistochemistry. The correlation between the expression of GOLPH3 in PTC and clinicopathologic characteristics and ATA risk of recurrence stratification was analyzed. Results: The mRNA level of GOLPH3 in PTC tissues was significantly higher than that in adjacent noncancerous tissues (7.53±1.32 vs 3.64±1.44, P<0.001). The protein expression level of GOLPH3 in PTC tissues was significantly higher than that in adjacent noncancerous tissues [66(30, 95) vs 34(20, 72), P<0.001]. The expression of GOLPH3 was significantly correlated to the tumor size (P=0.026), extrathyroid invasion (P=0.016), lymph node metastasis (P=0.001) and TNM stage (P=0.027) in PTC. Multivariate logistic regression analysis showed that GOLPH3 expression was independently correlated to tumor size (OR=3.58, 95%CI: 1.19-15.46, P=0.017) and lymph node metastasis (OR=7.28, 95%CI: 2.43-10.08, P=0.002). The expression of GOLPH3 was positively correlated to ATA risk of recurrence stratification (P=0.041). Conclusions: Overexpression of GOLPH3 is associated with the development of PTC and poor prognosis in patients with PTC. Detection of GOLPH3 expression can help evaluate proliferative and metastatic potential of PTC, as well as the risk of postoperative recurrence in patients with PTC.


Assuntos
Proteínas de Membrana/genética , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Metástase Linfática , Recidiva Local de Neoplasia , Fosfoproteínas , Prognóstico , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética
13.
DNA Cell Biol ; 38(11): 1249-1256, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31553233

RESUMO

Transmembrane protein 39A (TMEM39A) gene polymorphisms have been related to various autoimmune diseases, but the relationship between TMEM39A polymorphisms and autoimmune thyroid disease (AITD) remains unknown. This study was aimed at investigating whether the polymorphisms of the TMEM39A were associated with AITD in the Chinese Han population. A case-control study was performed in a total of 906 AITD patients and 744 healthy controls. Four single nucleotide polymorphisms, including rs1132200, rs12492609, rs2282175, and rs7629750, in TMEM39A were examined by polymerase chain reaction-ligase detection reaction. We found that the allele T of rs12492609 in TMEM39A was associated with AITD and Hashimoto's thyroiditis (HT) (p = 0.023; p = 0.028 respectively). Compared with controls, the frequency of haplotype CCA in AITD patients was higher than that in controls (p = 0.036), but the frequency of haplotype CTA in AITD and HT patients was lower than that in controls (p = 0.046; p = 0.047 respectively). In addition, the frequency of allele A at rs7629750 in AITD patients with onset age ≤18 years old was higher than that in AITD patients with onset age ≥19 (p = 0.046). Further, there was an obvious difference in the genotype distributions of rs12492609 and rs7629750 between HT patients with hypothyroidism and those without hypothyroidism (p = 0.034 and p = 0.023, respectively). Our study first reveals that the polymorphisms of the TMEM39A gene are associated with the susceptibility to AITD, especially for early-onset AITD and HT with hypothyroidism.


Assuntos
Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Tireoidite Autoimune/genética , Adolescente , Adulto , Idade de Início , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/genética , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/genética , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Tireoidite Autoimune/epidemiologia , Adulto Jovem
14.
J Agric Food Chem ; 67(40): 11119-11128, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525874

RESUMO

Xanthohumol (Xan) is a prenylated chalcone mainly found in hops; it has been demonstrated to function against hypercholesterolemia, hyperlipidemia, and atherosclerosis. In this study, we focused on the hypocholesterolemic effect of Xan on cholesterol uptake and the underlying molecular mechanisms of Xan in human intestinal Caco-2 cells. The microarray data showed that Niemann-Pick C1-like 1 (NPC1L1), an essential transporter for dietary cholesterol absorption, was significantly downregulated in Xan-treated Caco-2 cells. We demonstrated that Xan (10 and 20 µM) suppressed the mRNA and protein expression of NPC1L1 by 0.65 ± 0.12-fold and 0.54 ± 0.15-fold and 0.72 ± 0.04-fold and 0.44 ± 0.12-fold, respectively, compared to that of the vehicle-treated Caco-2 cells. Moreover, Xan (10 and 20 µM) significantly inhibited cholesterol uptake by approximately 12 and 32% in Caco-2 cells. NPC1L1 promoter activity was significantly suppressed by Xan, and a DNA element within the NPC1L1 promoter involved in Xan-mediated NPC1L1 reduction located between the -120 and -20 positions was identified. Moreover, Xan markedly decreased the mRNA and protein levels of hepatocyte nuclear factor 4α (HNF-4α), a critical activator of NPC1L1 transcription, and subsequently attenuated HNF-4α/NPC1L1 promoter complex formation, resulting in the suppression of NPC1L1 gene expression. Finally, we demonstrated that Xan markedly abolished lovastatin-induced NPC1L1 overexpression in Caco-2 cells. These findings reveal that Xan suppresses NPC1L1 expression via downregulation of HNF-4α and exerts inhibitory effects on cholesterol uptake in the intestinal Caco-2 cells. Our findings suggest Xan could serve as a potential cholesterol-lowering agent and supplement for statin therapy.


Assuntos
Colesterol/metabolismo , Flavonoides/farmacologia , Fator 4 Nuclear de Hepatócito/metabolismo , Proteínas de Membrana/genética , Propiofenonas/farmacologia , Anticolesterolemiantes/farmacologia , Transporte Biológico/efeitos dos fármacos , Células CACO-2 , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Fator 4 Nuclear de Hepatócito/genética , Humanos , Proteínas de Membrana/metabolismo , Regiões Promotoras Genéticas
15.
Chemosphere ; 226: 874-882, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31509916

RESUMO

The exposure and health effects of fluoride are an ongoing topic that has attracted worldwide attention. Fluoride exposure disturbs the testicular development, sexual hormone levels and spermatogenesis. However, as to whether fluoride interferes with acrosome formation which is essential for production of capable spermatozoa during spermatogenesis still remains unclear. The objective was to determine the effects of fluoride on the acrosome formation and to further elucidate the potential mechanism of impaired reproductive function. For this, forty adult rats were assigned into four groups. The control group received distilled water, while the other three groups were treated with 25, 50 and 100 mg NaF/L via drinking water for 56 d, respectively. Testes were processed for total RNA extraction and western blot analysis. Three samples of each group were fixed in 2.5% glutaraldehyde solution for transmission electron microscopy analysis. From the results, we first found that fluoride decreased the expression of mRNA and protein levels of Zpbp1, Spaca1 and Dpy19l2 of seven markers during acrosome biogenesis in testes. Furthermore, fluoride damaged not only the acrosome structure, but also the structure of the nuclear lamina which was observed to be discontinuous and partially missing by transmission electron microscopy. Moreover, the results indicated that the altered structure in nuclear lamina maybe due to reduced LMNB2 expression in testis induced by fluoride. In a nutshell, fluoride exposure could restrain acrosome biogenesis during spermatogenesis and contribute to the elucidation of the underlying mechanisms of fluoride-induced male reproductive toxicity.


Assuntos
Acrossomo/patologia , Fluoretos/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/patologia , Testículo/patologia , Acrossomo/efeitos dos fármacos , Acrossomo/metabolismo , Animais , Proteínas do Ovo/genética , Proteínas do Ovo/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas de Plasma Seminal/genética , Proteínas de Plasma Seminal/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 890-892, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515783

RESUMO

OBJECTIVE: To detect potential mutation in a Chinese pedigree affected with congenital limb malformations. METHODS: Clinical data was collected. Genomic DNA was extracted from peripheral blood samples of family members. The zone of polarizing activity regulatory sequence (ZRS) were amplified by PCR and subjected to direct sequencing. RESULTS: Among the 13 individuals in this pedigree, there were 4 PPD patients, who were characterized by varying degrees of deformity. The female patients suffered triphalangeal thumb and preaxial polydactyly, while the male patients only had preaxial polydactyly. Only one patient had foot involvement. TA heterogeneous mutations was discovered in the ZRS (105C>G) in all patients, the same mutation was not detected in 2 healthy family members. CONCLUSION: The inheritance pattern of PPD was autosomal dominant inheritance. There was a significant variability of symptoms among family patients. The heterozygous mutation of the ZRS (105C>G) probably underlie the disease.


Assuntos
Deformidades Congênitas da Mão/genética , Deformidades Congênitas dos Membros/genética , Proteínas de Membrana/genética , Polidactilia/genética , Feminino , Testes Genéticos , Humanos , Masculino , Linhagem , Polegar/patologia
18.
Rev Bras Parasitol Vet ; 28(3): 451-457, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31390434

RESUMO

The msp4 gene of A. marginale is unicodon, stable and mostly homogeneous, being considered as a useful marker for phylogeographic characterization of this bacterium. The objective of this work was to analyze the phylogeography of A. marginale based on the msp4 gene in beef cattle from the Brazilian Pantanal, compared to those found in other regions worldwide. The blood samples investigated were collected from 400 animals (200 cows and 200 calves) reared in five extensive breeding farms in this region. The results indicated that of the evaluated samples, 56.75% (227/400) were positive for A. marginale based on the msp1ß gene by quantitatitve PCR (qPCR), while 8.37% (19/227) were positive for the msp4 gene in the conventional PCR. In the Network distance analysis, 14 sequences from the Brazilian Pantanal were grouped into a single group with those from Thailand, India, Spain, Colombia, Parana (Brazil), Mexico, Portugal, Argentina, China, Venezuela, Australia, Italy and Minas Gerais (Brazil). Among 68 sequences from Brazil and the world, 15 genotypes were present while genotype number one (#1) was the most distributed worldwide. Both Splitstree and network analyses showed that the A. marginale msp4 sequences detected in beef cattle from the Brazilian Pantanal showed low polymorphism, with the formation of one genogroup phylogenetically related to those found in ruminants from South and Central America, Europe, and Asia.


Assuntos
Anaplasma marginale/genética , Proteínas de Bactérias/genética , Bovinos/microbiologia , Proteínas de Membrana/genética , Filogeografia/métodos , Américas , Sequência de Aminoácidos , Anaplasma marginale/isolamento & purificação , Animais , Ásia , Brasil , DNA Bacteriano/genética , Europa (Continente) , Feminino , Genótipo , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase
20.
Cancer Sci ; 110(10): 3122-3131, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31369178

RESUMO

Delta-like 3 (DLL3) is a member of the Delta/Serrate/Lag2 (DSL) group of Notch receptor ligands. Five DSL ligands are known in mammals, among which DLL3 has a unique structure. In the last few years, DLL3 has attracted attention as a novel molecular targeting gene in neuroendocrine carcinoma of the lung due to its high expression. However, the expression pattern and functions of DLL3 in the gastrointestinal tract and gastrointestinal neuroendocrine carcinoma remain unclear. In this study, we examined the expression and role of DLL3 in the gastrointestinal tract, as well as in gastrointestinal neuroendocrine carcinoma. Immunohistochemical staining of the human normal gastrointestinal tract revealed that DLL3 localized in neuroendocrine cells. DLL3 showed intense staining in chromogranin A-positive gastric cancer specimens. Real-time quantitative RT-PCR and western blotting analyses showed considerable upregulation of DLL3 in gastrointestinal neuroendocrine carcinoma cell lines. Immuno-electron microscopy demonstrated abundant expression of DLL3 in neurosecretory granules in these cells. Furthermore, gene silencing of DLL3 caused significant growth inhibition through the induction of intrinsic apoptosis. Our findings suggest that DLL3 is expressed in neuroendocrine cells of the gastrointestinal tract and that it has a pivotal role in gastrointestinal neuroendocrine carcinoma cells. Based on these findings, further investigations are required to achieve a breakthrough in developing therapeutic strategies for gastrointestinal neuroendocrine carcinoma.


Assuntos
Carcinoma Neuroendócrino/metabolismo , Neoplasias Gastrointestinais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Células Neuroendócrinas/metabolismo , Idoso , Apoptose , Carcinoma Neuroendócrino/genética , Linhagem Celular Tumoral , Neoplasias Gastrointestinais/genética , Trato Gastrointestinal/citologia , Trato Gastrointestinal/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Regulação para Cima
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