RESUMO

Glutathione synthetase deficiency (GSSD) is a rare inborn error of glutathione metabolism with autosomal recessive inheritance. The severe form of the disease is characterized by acute metabolic acidosis, usually present in the neonatal period with hemolytic anemia and progressive encephalopathy. A case of a male newborn infant who had severe metabolic acidosis with high anion gap, hemolytic anemia, and hyperbilirubinemia is reported. A high level of 5-oxoproline was detected in his urine and a diagnosis of generalized GSSD was made. DNA sequence analysis revealed the infant to be compound heterozygous with two mutations, c.738dupG in exon 8 of GSS gene resulting in p.S247fs and a repetitive sequence in exon 3 of GSS gene. Treatment after diagnosis of GSSD included supplementation with antioxidants and oral sodium hydrogen bicarbonate. However, he maintained a variable degree of metabolic acidosis and succumbed shortly after his parents requested discontinuation of therapy because of dismal prognosis and medical futility when he was 18 days old.

Assuntos

Erros Inatos do Metabolismo dos Aminoácidos/genética , Glutationa Sintase/deficiência , Mutação , Acidose/etiologia , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Ácido Glutâmico/análise , Glutationa Sintase/genética , Glutationa Sintase/metabolismo , Humanos , Recém-Nascido , Masculino , Piroglutamato Hidrolase/deficiência , Piroglutamato Hidrolase/genética , Análise de Sequência de DNA/métodos

RESUMO

Glutathione synthetase deficiency (GSSD) is a rare inborn error of glutathione metabolism with autosomal recessive inheritance. The severe form of the disease is characterized by acute metabolic acidosis, usually present in the neonatal period with hemolytic anemia and progressive encephalopathy. A case of a male newborn infant who had severe metabolic acidosis with high anion gap, hemolytic anemia, and hyperbilirubinemia is reported. A high level of 5-oxoproline was detected in his urine and a diagnosis of generalized GSSD was made. DNA sequence analysis revealed the infant to be compound heterozygous with two mutations, c.738dupG in exon 8 of GSS gene resulting in p.S247fs and a repetitive sequence in exon 3 of GSS gene. Treatment after diagnosis of GSSD included supplementation with antioxidants and oral sodium hydrogen bicarbonate. However, he maintained a variable degree of metabolic acidosis and succumbed shortly after his parents requested discontinuation of therapy because of dismal prognosis and medical futility when he was 18 days old.

Assuntos

Humanos , Masculino , Recém-Nascido , Erros Inatos do Metabolismo dos Aminoácidos/genética , Glutationa Sintase/deficiência , Mutação , Acidose/etiologia , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Ácido Glutâmico/análise , Glutationa Sintase/genética , Glutationa Sintase/metabolismo , Piroglutamato Hidrolase/deficiência , Piroglutamato Hidrolase/genética , Análise de Sequência de DNA/métodos

RESUMO

As a mechanism compensating for obstructive coronary artery disease, coronary collateral circulation (CCC) has attracted cardiologists for a long time to explore its potential impact. In the present study, Chinese patients suffering from ≥95% coronary stenosis, as diagnosed by angiography, have been investigated for the correlation between CCC and lipoprotein(a) [Lp(a)] levels. A cohort of 654 patients was divided into four categories according to Rentrop grades 0, 1, 2, and 3. Lp(a) levels were divided into model 1, discretized with critical values of 33 and 66%, and model 2, discretized with a cutoff value of 30.0 mg/dL. Furthermore, we evaluated the correlation between CCC and serum Lp(a) levels. The four groups had significantly different Lp(a) levels (25.80±24.72, 18.99±17.83, 15.39±15.80, and 8.40±7.75 mg/dL; P<0.001). In model 1, concerning R0, the risk in the third Lp (a) tertile (OR=3.34, 95%CI=2.32-4.83) was greater than that in the first tertile. In model 2, concerning R0, the risk in Lp(a) >30.0 group (OR=6.77, 95%CI=4.44-10.4) was greater than that of Lp(a) <30.0 mg/dL. The worst condition of CCC can be predicted independently by Lp(a) levels. In addition to clinical usage, Lp(a) levels can also be utilized as biological markers.

Assuntos

Circulação Colateral/fisiologia , Doença da Artéria Coronariana/sangue , Circulação Coronária/fisiologia , Oclusão Coronária/sangue , Lipoproteína(a)/sangue , Biomarcadores/sangue , Estudos de Coortes , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco

RESUMO

We investigated the expression level of p53 upregulated modulator of apoptosis (PUMA), myeloid cell leukemia-I (MCL-1), and p53 in renal cell carcinoma (RCC) and para-carcinoma tissues, as well as their clinical significance. The expression levels of PUMA, MCL-1, and p53 in RCC and para-carcinoma tissues were measured using immunohistochemical and quantitative real-time PCR methods. Correlations between protein expression and pathological characteristics were analyzed. Renal clear cell carcinoma showed elevated MCL-1 and p53 protein expression (P > 0.05) and reduced PUMA expression as compared to that in para-carcinoma tissues. Spearman ranking correlation analysis showed that expression of PUMA, MCL-1, and p53 in was negatively correlated with RCC (r = -0.504, P = 0.001; r = -0.413, P = 0.008). We also observed significant correlation between MCL-1 expression and tumor differentiation (P < 0.05), where MCL-1 expression was significantly higher in well-differentiated adenocarcinoma as compared to that in medium or lowly differentiated adenocarcinoma. In addition, p53 expression was highly correlated with TNM staging (P < 0.05). Single factor analysis on COX's proportional hazard model indicated that postoperative survival rate and prognosis of renal clear cell carcinoma was highly correlated with TNM staging (P < 0.05). Quantitative real-time PCR analysis indicated higher expression of PUMA, MCL-1, and p53 in cancer tissues as compared to that in para-carcinoma tissues (P < 0.05).The expression of PUMA, MCL-1, and p53 can reflect the biological behavior of renal cell carcinoma, and can be used to indicate tumor invasion, progression, and prognosis.

Assuntos

Proteínas Reguladoras de Apoptose/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteínas Proto-Oncogênicas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo

RESUMO

Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250-300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg·kg-1·day-1) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.

Assuntos

Benzofuranos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Inflamação/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Peroxidase/efeitos dos fármacos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais

RESUMO

As a mechanism compensating for obstructive coronary artery disease, coronary collateral circulation (CCC) has attracted cardiologists for a long time to explore its potential impact. In the present study, Chinese patients suffering from ≥95% coronary stenosis, as diagnosed by angiography, have been investigated for the correlation between CCC and lipoprotein(a) [Lp(a)] levels. A cohort of 654 patients was divided into four categories according to Rentrop grades 0, 1, 2, and 3. Lp(a) levels were divided into model 1, discretized with critical values of 33 and 66%, and model 2, discretized with a cutoff value of 30.0 mg/dL. Furthermore, we evaluated the correlation between CCC and serum Lp(a) levels. The four groups had significantly different Lp(a) levels (25.80±24.72, 18.99±17.83, 15.39±15.80, and 8.40±7.75 mg/dL; P<0.001). In model 1, concerning R0, the risk in the third Lp (a) tertile (OR=3.34, 95%CI=2.32-4.83) was greater than that in the first tertile. In model 2, concerning R0, the risk in Lp(a) >30.0 group (OR=6.77, 95%CI=4.44-10.4) was greater than that of Lp(a) <30.0 mg/dL. The worst condition of CCC can be predicted independently by Lp(a) levels. In addition to clinical usage, Lp(a) levels can also be utilized as biological markers.

Assuntos

Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Circulação Colateral/fisiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária/fisiologia , Oclusão Coronária/sangue , Lipoproteína(a)/sangue , Biomarcadores/sangue , Estudos de Coortes , Angiografia Coronária , Doença da Artéria Coronariana/fisiopatologia , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/fisiopatologia , Valor Preditivo dos Testes , Fatores de Risco

RESUMO

Comprehensive multi-omics data analyses have become an important means for understanding cancer incidence and progression largely driven by the availability of high-throughput sequencing technologies for genomes, proteomes, and transcriptomes. However, how tumor cells from the site of origin of the cancer begin to grow in other sites of the body is very poorly understood. In order to examine potential connections between different cancers and to gain an insight into the metastatic process, we conducted a multi-omics data analysis using data deposited in The Cancer Genome Atlas database. By combining somatic mutation data along with DNA methylation level and gene expression level data, we applied a Bayesian network analysis to detect the potential association among four distinct cancer types namely, Head and neck squamous cell carcinoma (Hnsc), Lung adenocarcinoma (Luad), Lung squamous cell carcinoma (Lusc), and Skin cutaneous melanoma (Skcm). Further validation based on the 'identification of somatic signatures' and the 'association rules analysis' confirmed these associations. Previous investigations have suggested that common risk factors and molecular abnormalities in cell-cycle regulation and signal transduction predominate among these cancers. This evidence indicates that our study provides a rational analysis and hopefully will help shed light on the links between different cancers and metastasis as a whole.

Assuntos

Metástase Neoplásica/genética , Teorema de Bayes , Análise Mutacional de DNA , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Genéticos , Mutação

RESUMO

Chronic obstructive pulmonary disease (COPD) is an important respiratory disease with high mortality. Although smoking is the major environmental risk factor for the development of COPD, only 10% of heavy smokers develop symptomatic disease, suggesting association between genetic susceptibilities and environmental influences. In recent years, as one of the most widely studied genes including tests for associations between a genetic variant and COPD, epoxide hydrolase 1 (EPHX1) was found to be involved in the metabolism of tobacco smoke, an important risk factor of COPD. However, genetic associations with COPD identified in studies on EPHX1 are controversial. To address this issue, except for performing the meta-analysis, which specially added our current study on two polymorphisms (T337C and A416G) of EPHX1, we performed combined data mining based on functional prediction algorithms of nonsynonymous single-nucleotide polymorphisms and gene-based variable threshold testing. Genetic variations in EPHX1 did not affect COPD in Caucasian and Eastern Asian population, which is supported by recent evidence. We found no association between EPHX1 and COPD; however, a minor effect of EPHX1 on COPD risk was not completely excluded; further replication studies with large samples are needed to confirm our findings.

Assuntos

Epóxido Hidrolases/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto

RESUMO

SQUAMOSA promoter-binding protein-like (SPL) proteins play crucial roles in plant growth, development, and responses to environmental stressors. The peanut (Arachis hypogaea L.) is a globally important oil crop. In this study, we cloned the full-length cDNA of 15 SPLs in the peanut by transcriptome sequencing and rapid amplification of cDNA ends, and analyzed their genomic DNA sequences. cDNA lengths varied significantly, from 369 to 3102 bp. The SBP domain of the peanut SPL proteins was highly conserved compared to SPLs in other plant species. Based on their sequence similarity to SPLs from other plant species, the peanut SPLs could be grouped into five subgroups. In each subgroup, lengths of individual genes, conserved motif numbers, and distribution patterns were similar. Seven of the SPLs were predicted to be targets of miR156. The SPLs were ubiquitously expressed in the roots, leaves, flowers, gynophores, and seeds, with different expression levels and accumulation patterns. Significant differences in the expression of most of the SPLs were observed between juvenile and adult leaves, suggesting that they are involved in developmental regulation. Dynamic changes occurred in transcript levels at stage 1 (aerial grown green gynophores), stage 2 (gynophores buried in soil for about three days), and stage 3 (gynophores buried in soil for about nine days with enlarged pods). Possible roles that these genes play in peanut pod initiation are discussed.

Assuntos

Arachis/metabolismo , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Arachis/genética , Sequência de Bases , Regulação da Expressão Gênica no Desenvolvimento , Genes de Plantas , MicroRNAs , Especificidade de Órgãos , Filogenia , Componentes Aéreos da Planta/genética , Componentes Aéreos da Planta/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , RNA Mensageiro , Alinhamento de Sequência , Análise de Sequência de DNA , Análise de Sequência de RNA , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo

RESUMO

Nucleotide-binding site (NBS) disease resistance genes play a crucial role in plant defense responses against pathogens and insect pests. Many NBS-encoding genes have been detected in Lotus japonicus, an important forage crop in many parts of the world. However, most NBS genes identified so far in L. japonicus were only partial sequences. We identified 45 full-length NBS-encoding genes in the L. japonicus genome, and analyzed gene duplications, motifs, and the molecular phylogeny to further understand the NBS gene family. We found that gene duplication events rarely occur in L. japonicus NBS-encoding (LjNBS) genes. In addition, LjNBS genes were subjected to selection pressure, and codon usage bias was evident. We tested for purifying selection (specifically in the CC-NBS-LRR and TIR-NBS-LRR groups), and found strong purifying selection in the TIR-domain-containing sequences, indicating that the CC-NBS-LRR group is more likely to undergo expansion than the TIR-NBS-LRR group. Moreover, our results showed that both selection and mutation contributed to LjNBS codon usage bias, but mutational bias was the major influence on codon usage.

Assuntos

Resistência à Doença/genética , Evolução Molecular , Genes de Plantas , Estudo de Associação Genômica Ampla , Lotus/genética , Motivos de Aminoácidos , Mapeamento Cromossômico , Códon , Biologia Computacional/métodos , Sequência Conservada , Bases de Dados Genéticas , Duplicação Gênica , Interações Hospedeiro-Patógeno , Lotus/classificação , Família Multigênica , Filogenia , Seleção Genética

RESUMO

Brain natriuretic peptide (BNP) has a protective effect on acute injury of the heart, brain, and lung. However, its role in acute kidney injury (AKI) remains unclear. The aim of this study was to investigate the effect of lyophilized recombinant human BNP (lrh-BNP) on AKI and the underlying molecular mechanisms. An experimental model for AKI was established using an ischemia/reperfusion (I/R) procedure. Healthy adult BALB/c mice were randomized to the sham, I/R, and lrh-BNP-treated post-I/R (BNP + I/R) groups. Post-operatively, the BNP + I/R group was subcutaneously injected with lrh-BNP (0.03 µg·kg(-1)·min(-1)), whereas the other groups received saline at the same dose. Serum creatinine (Scr) and blood urea nitrogen levels were examined; tissue staining was performed to evaluate the degree of I/R injury (IRI). Ki67 positive staining of renal tubular epithelial cells was observed using immunofluorescence confocal laser scanning to assess the effect of BNP on cell proliferation after IRI. Inflammatory factor expression levels were detected to evaluate the effect of BNP on renal inflammation. Compared with the sham group, the I/R group showed increased Scr levels, severe tubular injury of the renal outer medulla, increased Kim-1 mRNA expression, an increased number of infiltrative macrophages in the renal interstitium, and increased TNF-α, IL- 1ß, IL-6, MCP-1, and HIF-1α mRNA expression. BNP delivery significantly reduced all pathological changes in the I/R group. The protective role of BNP in murine renal IRI may be associated with its inhibition of renal interstitial inflammation and hypoxia and its promotion of renal tubule repair.

Assuntos

Injúria Renal Aguda/patologia , Injúria Renal Aguda/fisiopatologia , Peptídeo Natriurético Encefálico/farmacologia , Substâncias Protetoras/farmacologia , Proteínas Recombinantes/farmacologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Modelos Animais de Doenças , Epitélio/irrigação sanguínea , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/patologia , Humanos , Hipóxia/tratamento farmacológico , Hipóxia/etiologia , Hipóxia/metabolismo , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/patologia , Testes de Função Renal , Túbulos Renais/irrigação sanguínea , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Camundongos , Peptídeo Natriurético Encefálico/administração & dosagem , Substâncias Protetoras/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo

RESUMO

Baculovirus is the only virus that has been found to encode the ubiquitin protein. In this study, ubiquitin sequences from 16 insects and 49 viruses were collected and compared. The resulting sequences were aligned with virus genomes. Then MAGE 5.0, k-estimated software, as well as other software programs were used for systemic evolutionary, selection pressure, and evolutionary distance analysis. The results of the pairwise ratio of non-synonymous to synonymous substitution values and evolutionary distances showed that ubiquitin from baculovirus and insect hosts have been under purifying selection during evolution and are thus evolutionarily conserved. Moreover, genes from insect hosts were more conserved than those in baculovirus. Analysis of the non-synonymous to synonymous substitution rates at each site and entropy calculations revealed the evolutionary status of every site in the ubiquitin genes of baculovirus and their hosts. Genome locations and phylogenetic trees indicated that granuloviruses and non-photosynthetic vegetation evolved, and granulovirus evolution was more similar to that of insect hosts. Our results suggest that the ubiquitin gene in baculovirus may have been acquired through horizontal transfer from the host.

Assuntos

Baculoviridae/genética , Evolução Molecular , Insetos/genética , Ubiquitina/genética , Motivos de Aminoácidos , Substituição de Aminoácidos , Animais , Baculoviridae/classificação , Biologia Computacional , DNA Complementar/genética , Variação Genética , Genoma Viral , Filogenia , Matrizes de Pontuação de Posição Específica , Seleção Genética

RESUMO

The aim of this study was to identify the factors related to and determine the prevalence of Parkinson's disease (PD) among Uygur residents in Hetian Prefecture, Xinjiang Uygur Autonomous Region. This population-based prospective cohort study used structured questionnaires to screen for factors related to PD. The prevalence in different age groups was analyzed, and PD risk was assessed using univariate and multivariate conditional logistic regression analysis. In total, 5932 subjects participated in the survey; of these, 88 individuals, all of whom were Uygurs, had PD. The overall prevalence of PD was 1.48% (1.32%) in people over the age of 45; the prevalence was 1.68% (1.59%) in men and 1.28% (1.36%) in women. The Fifth Population Census in China found the prevalence of PD in Hetian, Xinjiang, to be 1.32%. Single-factor results showed that exercise, social activities, and frequent consumption of nuts are protective factors for PD, and long-term pesticide exposure, family history of PD, and consumption of barbecued food were risk factors for this condition. Multi-factor conditional logistic regression analysis showed that participation in sports and social activities can reduce the risk of PD, whereas long-term pesticide exposure and family history of PD increases this risk. These results show that PD is caused by the interaction of several factors.

Assuntos

Doença de Parkinson/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários

RESUMO

Recent genome-wide association studies identified 11 risk loci in different populations of familial and sporadic Parkinson's disease (PD) patients. Few loci have been verified in different European and Asian populations. We also validated 2 new single-nucleotide polymorphisms, rs947211 and rs823144, in PARK16 to explore their association with susceptibility to PD in the Xinjiang Uygur and Han populations. This case-control study included 312 PD patients (130 Uygur and 182 Han) and 359 control subjects (179 Uygur and 180 Han). Polymerase chain reaction-restriction fragment length polymorphism analysis and DNA sequencing were used to detect the rs947211 and rs823144 polymorphism in the PARK16 gene between the Xinjiang Uygur and Han populations. Frequencies of the A allele and AA genotype (42.1 and 15.7%, respectively) of rs947211 in PD patients were significantly lower than those in the control group (54.7 and 28.7%, respectively, P < 0.01). A allele and AA genotype frequencies of rs823144 were 56.8 and 31.8% in the PD patients group and were 54.1 and 29.3% in the control group; no significant difference was found (P > 0.05). In both the Han and Uygur groups, the rs947211 polymorphism was associated with PD. Haplotype analysis also indicated that the A-A and G-A haplotypes were associated with PD. We found that the rs947211 polymorphism may be a susceptibility marker for PD in the Chinese population; the A-A and G-A haplotypes may be a protective factor and a risk factor, respectively, for PD in the Chinese population.

Assuntos

Doença de Parkinson/genética , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , China , Etnicidade/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único

RESUMO

Objective: To study clinical semi-permeability tolerance level in the field of dental restoration. Method: Vita 95 enamel porcelain powder was adopted and 6.0% used as the control transmissivity. Discoid porcelain plates with different transmissivity, namely increasing transmissivity (0.25%, 0.5%, 1.0%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4% and 4.5%) and decreasing transmissivity (-0.25%, -0.5%, -1.0%, -1.5%, -2%, -2.5%, -3% and -3.5%) were made. Forty observers judged these according to six grades: same, similar, slightly different, visibly different, recognizable and significantly different, and under the observation conditions of a neutral grey background and 45°/0° lighting. The judgment results were analysed statistically. Results: When the transmissivity of the control porcelain plates was 6.032%, and the transmissivity of test porcelain plates decreased by 1% or increased by 3%, observers could find slight differences between the test samples and the control samples. When transmissivity of test samples decreased by 2.5% or increased by 4.5%, observers thought that the two porcelain plates belonged to different orders of magnitude. Conclusions: Under the experimental conditions, the upper and lower limits of clinical semi-permeability tolerance were 3% and 1%, respectively.

RESUMO

This study aimed to provide data for imaging diagnosis and clinical surgical plans by reconstructing a three-dimensional (3-D) digital visible heart model of single ventricle (SV) connection with aortic coarctation (CoA) and characterizing the myocardial and vascular wall pathological characteristics. Fifteen miscarried fetus cadavers with SV and CoA were selected. Fourteen cardiac specimens were systematically reviewed for segmental anatomy and conventional histological examinations. One fetus cadaver was used to obtain the structural dataset of the fetal body and to reconstruct a 3-D digital visible heart model. Specimen pathological dissection indicated hypertrophic myocardium SV, significant aortic wall thickening, and localized coarctation area elevation. Ten cases of SV with left ventricular morphology displayed a large muscle ridge and solitus normally aligned great arteries. Five cases of SV with right ventricular morphology had coarse, parallel trabeculations and received a common atrioventricular valve. The reconstructed 3-D heart and the main internal structures were realistic, which were beneficial for clinical and image teaching of fetal heart development. The change of characteristics of the myocardium and great vascular wall was obvious and may be the critical cause leading to progressive dysfunction in the postnatal heart.

Assuntos

Coartação Aórtica/diagnóstico , Coração Fetal/anormalidades , Coração Fetal/patologia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/patologia , Imageamento Tridimensional/métodos , Aorta/patologia , Coartação Aórtica/patologia , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X

RESUMO

Diallyl disulfide (DADS) inhibits growth and induces cell cycle G2/M arrest in human gastric cancer MGC803 cells. In this study, 15 mg/L DADS exerted similar effects on growth and cell cycle arrest in human gastric cancer BGC823 cells. Due to the importance of cell cycle redistribution in DADS-mediated anti-carcinogenic effects, we investigated the role of checkpoint kinases (Chk1 and Chk2) during DADS-induced cell cycle arrest. We hypothesized that DADS could mediate G2/M phase arrest through either Chk1 or Chk2 signal transduction pathways. We demonstrated that DADS induced the accumulation of phosphorylated Chk1, but not of Chk2, and that DADS down-regulated Cdc25C and cyclin B1. The expression of mRNA and total protein for Chkl and Chk2 was unchanged. Chk1 is specifically phosphorylated by ATR (ATM-RAD3-related gene). Western blot analysis showed that phospho-ATR was activated by DADS. Taken together, these data suggest that cell cycle G2/M arrest, which was associated with accumulation of the phosphorylated forms of Chk1, but not of Chk2, was involved in the growth inhibition induced by DADS in the human gastric cancer cell line BGC823. Furthermore, the DADS-induced G2/M checkpoint response is mediated by Chk1 signaling through ATR/Chk1/Cdc25C/cyclin B1, and is independent of Chk2.

Assuntos

Compostos Alílicos/farmacologia , Antineoplásicos/farmacologia , Dissulfetos/farmacologia , Fase G2/efeitos dos fármacos , Inibidores do Crescimento/farmacologia , Proteínas Quinases/efeitos dos fármacos , Neoplasias Gástricas/enzimologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quinase 1 do Ponto de Checagem , Humanos , Proteínas Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/patologia

RESUMO

Diallyl disulfide (DADS) inhibits growth and induces cell cycle G2/M arrest in human gastric cancer MGC803 cells. In this study, 15 mg/L DADS exerted similar effects on growth and cell cycle arrest in human gastric cancer BGC823 cells. Due to the importance of cell cycle redistribution in DADS-mediated anti-carcinogenic effects, we investigated the role of checkpoint kinases (Chk1 and Chk2) during DADS-induced cell cycle arrest. We hypothesized that DADS could mediate G2/M phase arrest through either Chk1 or Chk2 signal transduction pathways. We demonstrated that DADS induced the accumulation of phosphorylated Chk1, but not of Chk2, and that DADS down-regulated Cdc25C and cyclin B1. The expression of mRNA and total protein for Chkl and Chk2 was unchanged. Chk1 is specifically phosphorylated by ATR (ATM-RAD3-related gene). Western blot analysis showed that phospho-ATR was activated by DADS. Taken together, these data suggest that cell cycle G2/M arrest, which was associated with accumulation of the phosphorylated forms of Chk1, but not of Chk2, was involved in the growth inhibition induced by DADS in the human gastric cancer cell line BGC823. Furthermore, the DADS-induced G2/M checkpoint response is mediated by Chk1 signaling through ATR/Chk1/Cdc25C/cyclin B1, and is independent of Chk2.

Assuntos

Humanos , Compostos Alílicos/farmacologia , Antineoplásicos/farmacologia , Dissulfetos/farmacologia , /efeitos dos fármacos , Inibidores do Crescimento/farmacologia , Proteínas Quinases/efeitos dos fármacos , Neoplasias Gástricas/enzimologia , Linhagem Celular Tumoral , Divisão Celular/efeitos dos fármacos , Proteínas Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/patologia

RESUMO

Las asociaciones malformativas nos dan la clave para comprender la embriogénesis de sus componentes.El objetivo de nuestro trabajo es comparar las malformaciones esqueléticas(ME)de un modelo teratogénico de atresia de esófago(AE) en fetos de ratas con ME de la AE clínica y esbozar un posible mecanismo patogénico común.Para ello revisamos las historias y radiografías de 443 niños con AE tratados entre los años 1965 y 1996.Se indujo la aparición de AE en las camadas de 16 ratas mediante la inyección de adriamicina en los días 8 y 9 de la gestación.A los embriones recuperados se les tiño el esqueleto de azul alcián y rojo alizarina para evidenciar la presencia de anomalías.De los 443 pacientes estudiados,239(53,9 por ciento)tenían una o más malformaciones esqueléticas asociadas,siendo las más frecuentes:hipersegmentación vertebral(n=102)hipoplasia sacra(n=42)vértebras malformadas principalmente torácicas(n=47) e hipoplasia radial y del pulgar(n=57).De 52 embriones de rata con atresia de esófago todos ellos tenían alguna anomalía esquelética,siendo frecuentes las vértebras torácicas malformadas(n=52) y la hipoplasia sacra(n=27).La asociación de malformaciones esofágicas,vertebrales y de los miembros en el mismo individuo,sugiere que estas anomalías se deben a un mecanismo patogénico común tanto en la rata,como en el humano,capaces de alterar tanto la segmentación como la organización del mesodermo paraxial durante la organogénesis.La naturaleza de las malformaciones encontradas sugiere que los genes Hox podrían estar involucrados en la etiología de la AE

Assuntos

Animais , Camundongos , Atresia Esofágica/cirurgia , Anormalidades Congênitas , Esqueleto

RESUMO

Las asociaciones malformativas nos dan la clave para comprender la embriogénesis de sus componentes.El objetivo de nuestro trabajo es comparar las malformaciones esqueléticas(ME)de un modelo teratogénico de atresia de esófago(AE) en fetos de ratas con ME de la AE clínica y esbozar un posible mecanismo patogénico común.Para ello revisamos las historias y radiografías de 443 niños con AE tratados entre los años 1965 y 1996.Se indujo la aparición de AE en las camadas de 16 ratas mediante la inyección de adriamicina en los días 8 y 9 de la gestación.A los embriones recuperados se les tiño el esqueleto de azul alcián y rojo alizarina para evidenciar la presencia de anomalías.De los 443 pacientes estudiados,239(53,9 por ciento)tenían una o más malformaciones esqueléticas asociadas,siendo las más frecuentes:hipersegmentación vertebral(n=102)hipoplasia sacra(n=42)vértebras malformadas principalmente torácicas(n=47) e hipoplasia radial y del pulgar(n=57).De 52 embriones de rata con atresia de esófago todos ellos tenían alguna anomalía esquelética,siendo frecuentes las vértebras torácicas malformadas(n=52) y la hipoplasia sacra(n=27).La asociación de malformaciones esofágicas,vertebrales y de los miembros en el mismo individuo,sugiere que estas anomalías se deben a un mecanismo patogénico común tanto en la rata,como en el humano,capaces de alterar tanto la segmentación como la organización del mesodermo paraxial durante la organogénesis.La naturaleza de las malformaciones encontradas sugiere que los genes Hox podrían estar involucrados en la etiología de la AE

Assuntos

Animais , Camundongos , Anormalidades Congênitas , Esqueleto , Atresia Esofágica/cirurgia