RESUMO
PURPOSE: To examine the possible prognostic factors in patients with type 1 and type 2 papillary renal cell carcinoma (pRCC) after surgical management and to identify the independent predictive factors of the prognosis. METHODS: From 2010 to 2017, 1405 patients underwent surgery for renal cell carcinoma, of whom 114 had type 1 or type 2 pRCC and follow-up data were available for 88 patients. Clinicopathological and prognostic parameters were compared between type 1 and type 2 pRCC. Possible prognostic factors were retrospectively analyzed by univariate and multivariate analyses with Cox regression. RESULTS: The study included 63 males and 25 females with a mean age of 54.27 ± 12.91. 53 patients were diagnosed by regular physical examination and others presented with hematuria or lumbago. 53 (60.2%) underwent radical nephrectomy and 35 (39.8%) underwent nephron sparing surgery. After a mean follow-up of 46.08 ± 22.65 months, 16 patients died of pRCC metastasis and the 5-year disease-specific survival was 79.3%. The comparison of the 39 (44.3%) type 1 and 49 (55.7%) type 2 pRCCs revealed that type 2 pRCC had significantly higher grade and worse prognosis. Univariate analysis showed that symptomatic diagnosis, type, grade, and tumor stage were prognostic factors. Multivariate analysis identified that type and tumor stage were independent factors of the prognosis. CONCLUSIONS: Pathological type and tumor stage could serve as independent factors for the prognosis of patients with pRCC.
Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Adulto , Idoso , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/classificação , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefrectomia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Quinazolinas/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Irradiação Craniana/métodos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Bevacizumab/uso terapêutico , Neoplasias Pulmonares/patologia , Antineoplásicos/uso terapêutico , Fatores de Tempo , Análise de Variância , Resultado do Tratamento , Gefitinibe , MutaçãoRESUMO
Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.
Assuntos
Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Irradiação Craniana/métodos , Neoplasias Pulmonares/patologia , Quinazolinas/uso terapêutico , Adulto , Idoso , Análise de Variância , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/secundário , Terapia Combinada/métodos , Intervalo Livre de Doença , Receptores ErbB/análise , Receptores ErbB/genética , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
This study aimed to investigate the effects of heme oxygenase-1 recombinant Lactococcus lactis (LL-HO-1) on the intestinal barrier of rats with hemorrhagic shock. One hundred Sprague-Dawley male rats (280-320 g) were randomly divided into healthy control group (N group) and hemorrhagic shock group (H group). Each group was subdivided into HO1t, HO2t, HO3t, PBS and LL groups in which rats were intragastrically injected with LL-HO-1 once, twice and three times, PBS and L. lactis (LL), respectively. The mortality, intestinal myeloperoxidase (MPO) activity, intestinal contents of TNF-α, IL-10 and HO-1, and intestinal Chiu's score were determined. Results showed that in N group, the HO-1 content increased after LL-HO-1 treatment, and significant difference was observed in HO1t group and HO2t group (P<0.05). In H groups, MPO activity and Chiu's score decreased, but IL-10 content increased in LL-HO-1-treated groups when compared with PBS and LL groups (P<0.05). When compared with N group, the MPO activity reduced dramatically in LL-HO-1-treated groups. Thus, in healthy rats (N group), intragastrical LL-HO-1 treatment may increase the intestinal HO-1 expression, but has no influence on the intestinal barrier. In hemorrhagic shock rats, LL-HO-1 may significantly protect the intestinal barrier, and repeating the intragastrical LL-HO-1 treatments twice has the most obvious protection.
Assuntos
Heme Oxigenase-1/uso terapêutico , Lactococcus lactis , Choque Hemorrágico/prevenção & controle , Animais , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
The aim of this study was to investigate whether exogenous retinoic acid (RA) can upregulate the mRNA and protein expression of growth-associated protein 43 (GAP-43), thereby promoting brain functional recovery in a rat distal middle cerebral artery occlusion (MCAO) model of ischemia. A total of 216 male Sprague Dawley rats weighing 300-320 g were divided into 3 groups: sham-operated group, MCAO+vehicle group and MCAO+RA group. Focal cortical infarction was induced with a distal MCAO model. The expression of GAP-43 mRNA and protein in the ipsilateral perifocal region was assessed using qPCR and immunocytochemistry at 1, 3, 7, 14, 21, and 28 days after distal MCAO. In addition, an intraperitoneal injection of RA was given 12 h before MCAO and continued every day until the animal was sacrificed. Following ischemia, the expression of GAP-43 first increased considerably and then decreased. Administration of RA reduced infarction volume, promoted neurological functional recovery and upregulated expression of GAP-43. Administration of RA can ameliorate neuronal damage and promote nerve regeneration by upregulating the expression of GAP-43 in the perifocal region after distal MCAO.
Assuntos
Proteína GAP-43/metabolismo , Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Tretinoína/farmacologia , Regulação para Cima/efeitos dos fármacos , Animais , Isquemia Encefálica/prevenção & controle , Proteína GAP-43/genética , Imuno-Histoquímica , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Distribuição Aleatória , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
The aim of this study was to investigate whether exogenous retinoic acid (RA) can upregulate the mRNA and protein expression of growth-associated protein 43 (GAP-43), thereby promoting brain functional recovery in a rat distal middle cerebral artery occlusion (MCAO) model of ischemia. A total of 216 male Sprague Dawley rats weighing 300–320 g were divided into 3 groups: sham-operated group, MCAO+vehicle group and MCAO+RA group. Focal cortical infarction was induced with a distal MCAO model. The expression of GAP-43 mRNA and protein in the ipsilateral perifocal region was assessed using qPCR and immunocytochemistry at 1, 3, 7, 14, 21, and 28 days after distal MCAO. In addition, an intraperitoneal injection of RA was given 12 h before MCAO and continued every day until the animal was sacrificed. Following ischemia, the expression of GAP-43 first increased considerably and then decreased. Administration of RA reduced infarction volume, promoted neurological functional recovery and upregulated expression of GAP-43. Administration of RA can ameliorate neuronal damage and promote nerve regeneration by upregulating the expression of GAP-43 in the perifocal region after distal MCAO.
Assuntos
Animais , Masculino , Proteína GAP-43/metabolismo , Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Tretinoína/farmacologia , Regulação para Cima/efeitos dos fármacos , Isquemia Encefálica/prevenção & controle , Proteína GAP-43/genética , Imuno-Histoquímica , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Distribuição Aleatória , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
In recent years, Guangxi has become one of the most severely affected provinces by epidemics of avian cholera in China. To date, the major determinant climatic factors of the disease in the region have remained largely unknown, making it difficult to effectively target countermeasures for avian cholera surveillance and control. This study aimed to quantify the relationship between climatic variables and cases of avian cholera in subtropical areas of China. Data relating to local meteorological variables and notified cases of avian cholera were supplied by the relevant authorities between January 2006 and December 2015. Spearman correlation, co-linearity statistics and cross-correlation analysis were applied to the data, controlling for co-linearity and lag effects. A time-series Poisson regression analysis was conducted to examine the degree of correlation between the climate variables and avian cholera transmission. The results indicated that monthly mean temperature, relative humidity, rainfall and the multivariate El Niño Southern Oscillation Index, with 2-3 months lag, were correlated with avian cholera incidence. The final model had good predictive ability for the occurrence of avian cholera. Overall, the findings indicate that climate variability plays an important role in avian cholera transmission in Guangxi province. Adoption of the model presented in this study could usefully inform avian cholera surveillance strategies, making them significantly simpler and more effective. The model could also serve as a decision support tool for veterinary professionals and health authorities.
Assuntos
Animais , Aves Domésticas/anormalidades , Aves Domésticas/crescimento & desenvolvimento , Cólera/diagnóstico , Cólera/veterinária , Distribuição de Poisson , Zonas ClimáticasRESUMO
In recent years, Guangxi has become one of the most severely affected provinces by epidemics of avian cholera in China. To date, the major determinant climatic factors of the disease in the region have remained largely unknown, making it difficult to effectively target countermeasures for avian cholera surveillance and control. This study aimed to quantify the relationship between climatic variables and cases of avian cholera in subtropical areas of China. Data relating to local meteorological variables and notified cases of avian cholera were supplied by the relevant authorities between January 2006 and December 2015. Spearman correlation, co-linearity statistics and cross-correlation analysis were applied to the data, controlling for co-linearity and lag effects. A time-series Poisson regression analysis was conducted to examine the degree of correlation between the climate variables and avian cholera transmission. The results indicated that monthly mean temperature, relative humidity, rainfall and the multivariate El Niño Southern Oscillation Index, with 2-3 months lag, were correlated with avian cholera incidence. The final model had good predictive ability for the occurrence of avian cholera. Overall, the findings indicate that climate variability plays an important role in avian cholera transmission in Guangxi province. Adoption of the model presented in this study could usefully inform avian cholera surveillance strategies, making them significantly simpler and more effective. The model could also serve as a decision support tool for veterinary professionals and health authorities.(AU)
Assuntos
Animais , Aves Domésticas/anormalidades , Aves Domésticas/crescimento & desenvolvimento , Cólera/diagnóstico , Cólera/veterinária , Zonas Climáticas , Distribuição de PoissonRESUMO
Transgene silencing, which is common in transgenic plants and animals, limits the generation and application of genetically modified organisms, and is associated with the exogenous gene copy number, the methylation status of its promoters, and histone modification abnormalities. Here, we analyzed the expression of the exogenous gene DsRed and the methylation status of its cytomegalovirus (CMV) promoter in six healthy transgenic cashmere goats and transgenic nuclear donor cells. The CMV promoter exhibited high methylation levels (74.4-88.2%) in four of the goats, a moderate methylation level (58.7%) in one, and a low methylation level (21.2%) in one, while the methylation level of the transgenic nuclear donor cells was comparatively low (14.3%). DsRed expression was negatively correlated with promoter methylation status. Transgenic cashmere goats carried one to three copies of the CMV promoter fragment and one to six copies of the DsRed fragment, but copy number showed no obvious correlation with DsRed expression. After treatment with the methylation inhibitor 5-azacytidine, DsRed expression in transgenic goat cells significantly increased and CMV promoter methylation significantly decreased; this indicated an inverse correlation between promoter methylation status and DsRed expression. After treatment with the histone deacetylase inhibitor trichostatin A, DsRed expression increased, indicating that an abnormal histone modification in transgenic goats is also involved in exogenous gene silencing. These findings indicate the potential of trichostatin A and 5-azacytidine to rescue the biological activity of silenced exogenous transgenes in adult-derived transgenic cells under culture conditions.
Assuntos
Azacitidina/farmacologia , Cabras/genética , Histonas/genética , Ácidos Hidroxâmicos/farmacologia , Proteínas Luminescentes/genética , Regiões Promotoras Genéticas/efeitos dos fármacos , Animais , Animais Geneticamente Modificados , Citomegalovirus/genética , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA/efeitos dos fármacos , Feminino , Dosagem de Genes , Expressão Gênica , Inativação Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Histonas/metabolismo , Proteínas Luminescentes/agonistas , Proteínas Luminescentes/antagonistas & inibidores , Proteínas Luminescentes/metabolismo , Masculino , TransgenesRESUMO
The aim of this study was to identify core pathways associated with juvenile idiopathic arthritis (JIA) using the attract method. Kyoto Encyclopedia of Genes and Genomes pathways were determined using the GSEA-ANOVA method, based on the gene expression data of JIA. Syn-expression groups within core attractor pathways were identified by hierarchical clustering. Correlated sets of genes exhibiting highly similar profiles to the syn-expression groups were identified and each correlated set was subjected to a gene ontology functional enrichment analysis to discover potentially shared biological themes. Based on a false-discovery rate < 0.05, we identified 11 significant pathways were identified as potential attractors. Flag genes or uninformative genes were removed and 5 discriminative pathways: the proteasome, ribosome, protein export, spliceosome, and Parkinson's disease pathways were identified. A final set of syn-expression groups with a consistent trend of relative expression of pathway-related genes was obtained; that is, the proteasome, ribosome, protein export, spliceosome, and Parkinson's disease pathways were composed of 2, 2, 1, 2, and 3 clusters, respectively. Genes in each correlated set shared common roles, and changes at the pathway level were more likely to be real. In light of these, the attract method was able to on expand important context to find distinguishing expression patterns within pathways. This paper predicted that the functional themes involved in protein synthesis (such as proteasome, ribosome, spliceosome) were closely related to the progression of JIA, which might contribute to the detection of therapy target for JIA.
Assuntos
Artrite Juvenil/metabolismo , Artrite Juvenil/genética , Estudos de Casos e Controles , Criança , Análise por Conglomerados , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Redes e Vias Metabólicas , TranscriptomaRESUMO
This study aimed to predict pathogenic genes of childhood asthma based on molecular interaction networks and gene expression data. Known pathogenic genes identified from the human protein-protein interaction network were denoted as seed genes, and were included in network A. We extracted sub-network B (pathogenic network), which consisted of genes that interacted with at least two seed genes. We assigned a weight to select the pathogenic genes from this network according to its interactions and co-expressions with the seed genes. We also conducted ClusterONE analysis for the pathogenic network, and determined the statistical significance of the predicted clusters through a significance score (SS). Lastly, we investigated the biological pathways of the seed and candidate genes based on information obtained from the KEGG database. In network A, we identified 172 interactions and 125 genes that interacted with seed genes. In the pathogenic network, we found 51 genes and 102 interactions. The top 10 candidate genes with high weight scores were recorded. The SS of the predicted clusters demonstrated that 3 gene clusters were statistically relevant for childhood asthma. Pathway analysis showed that the seed genes and the top 10 candidate genes were significantly enriched in the same three biological processes. NFKBIA and BIRC3, which were involved in all three biological processes, may therefore be pathogenic genes. Using the network approach, we predicted that the pathogenic genes NFKBIA and BIRC3 are associated with childhood asthma. This information can provide guidelines for future experimental verification of childhood asthma.
Assuntos
Asma/genética , Redes Reguladoras de Genes , Proteínas I-kappa B/genética , Proteínas Inibidoras de Apoptose/genética , Mapas de Interação de Proteínas , Ubiquitina-Proteína Ligases/genética , Proteína 3 com Repetições IAP de Baculovírus , Estudos de Casos e Controles , Criança , Humanos , Inibidor de NF-kappaB alfaRESUMO
We conducted a case-control study to investigate the role of ERCC2 rs13181 polymorphism in glioma development. A total of 165 patients who were histopathologically diagnosed to have gliomas and 330 controls were collected at Jiujiang First People's Hospital between July 2012 and June 2014. The ERCC2 rs13181 polymorphism was analyzed using a polymerase chain reaction -restriction fragment length polymorphism assay. By conditional regression analysis, we found that the GG genotype of the ERCC2 rs13181 polymorphism is associated with susceptibility to gliomas when compared to the TT genotype (OR = 2.05, 95%CI = 1.11-3.79). In the recessive model, the GG genotype is associated with an increased risk of gliomas when compared with the TT+TG genotype (OR = 1.87, 95%CI = 1.03-3.37). In conclusion, the ERCC2 rs13181 polymorphism is correlated with an increased risk of gliomas in codominant and recessive models, which suggests that this polymorphism could influence the etiology of gliomas.
Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Glioma/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Adulto , Idoso , Povo Asiático , Feminino , Genótipo , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Euroleon coreanus (Okamoto) is widely distributed in China, and the larval stage can be treated as traditional Chinese medicine. However, the host-bacterium relationship remains unexplored, as there is a lack of knowledge on the microbial community of ant lions. Hence, in the current study, we explored the microbial community of the larval ant lion E. coreanus using Illumina MiSeq sequencing. Results indicated that a total of 10 phyla, 126 genera, and 145 species were characterized from the second instars of E. coreanus, and most of the microbes were classified in the phylum Proteobacteria. Cronobacter muytjensii was the most abundant species characterized in the whole body and gut of E. coreanus, and the unclassified species in the genera Brevundimonas and Lactobacillus were relatively more abundant in the head and carcass. In addition, no Wolbachia-like bacteria were detected, whereas bacteria like Francisella tularensis subsp. Holarctica OSU18 and unclassified Rickettsiella were first identified in ant lion E. coreanus.
Assuntos
Insetos/microbiologia , Animais , Bactérias , China , Larva/microbiologiaRESUMO
BACKGROUND AND AIMS: The relationship between multiple lifestyle components analyzed in combination and inflammation remains understudied. We aimed to assess the association between a Healthy Lifestyle Score (HLS) that includes adherence to five behavioral components (diet, physical activity and sedentary behaviors, smoking, social support and network, and sleep) and inflammatory markers, as well as the role of the HLS in inflammation among individuals with cardiometabolic conditions, in Puerto Rican adults. METHODS AND RESULTS: In a cross-sectional study of 842 Puerto Ricans adults (aged 45-75 y) living in Boston, MA, the HLS (range = 0-190; maximum indicative of healthiest adherence) was analyzed for association with three inflammatory markers: interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). In multivariable-adjusted models, the HLS was inversely associated with IL-6 (ß ± SE = -0.55 ± 0.13; P < 0.001) and TNF-α (-0.39 ± 0.13; P = 0.004). The dietary and smoking components were associated with both inflammatory markers independently of the other HLS components. Significant inverse associations were observed for each 20-unit increase in HLS and IL-6 and TNF-α for participants with hypertension (n = 600; ß ± SE = -0.58 ± 0.16; -0.46 ± 0.16, respectively) and with overweight/obesity (n = 743; ß ± SE = -0.59 ± 0.13; -0.50 ± 0.14, respectively), but not for those with diabetes (n = 187) or heart disease (n = 192). The HLS was not associated with CRP, after adjustment for potential confounders. CONCLUSION: Higher adherence to multiple lifestyle behaviors was associated with lower concentrations of inflammatory markers. Because low-grade inflammation may precede chronic diseases, following an overall healthy lifestyle may help lower risk of these diseases.
Assuntos
Biomarcadores/sangue , Estilo de Vida Saudável , Inflamação/sangue , Idoso , Boston/epidemiologia , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Dieta Saudável , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Hipertensão/sangue , Hipertensão/etnologia , Hipertensão/prevenção & controle , Inflamação/etnologia , Inflamação/prevenção & controle , Interleucina-6/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etnologia , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , Avaliação Nutricional , Obesidade/sangue , Obesidade/prevenção & controle , Porto Rico/etnologia , Fatores de Risco , Comportamento Sedentário , Sono , Fumar , Apoio Social , Fator de Necrose Tumoral alfa/sangueRESUMO
Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=â¼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.
Assuntos
Cardiopatias/fisiopatologia , Fator 88 de Diferenciação Mieloide/metabolismo , Remodelação Ventricular/fisiologia , Animais , Fator Natriurético Atrial/metabolismo , Western Blotting , Ecocardiografia , Cardiopatias/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Masculino , Camundongos , Camundongos Transgênicos , Fator 88 de Diferenciação Mieloide/genética , Contração Miocárdica/fisiologia , Miocárdio/patologia , Peptídeo Natriurético Encefálico/metabolismo , Escores de Disfunção Orgânica , Tamanho do Órgão , Fenótipo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=∼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.
Assuntos
Animais , Masculino , Coelhos , Remodelação Ventricular/fisiologia , Fator 88 de Diferenciação Mieloide/metabolismo , Cardiopatias/fisiopatologia , Tamanho do Órgão , Camundongos Transgênicos , Ecocardiografia , Western Blotting , Fator Natriurético Atrial/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Escores de Disfunção Orgânica , Cardiopatias/metabolismo , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/patologia , Contração Miocárdica/fisiologia , Miocárdio/patologiaRESUMO
An antifungal protein exhibiting a high activity against Sclerotinia sclerotiorum in vivo was purified by ammonium sulfate precipitation, hydrophobic chromatography, and gel filtration chromatography from the culture filtrate of the endophytic Bacillus subtilis strain Em7. The protein was characterized as a ß-1,3-1,4-glucanase according to amino acid analysis, and showed excellent properties in thermal stability and acid resistance. At the same time, the antifungal protein was cloned and heterologously expressed in Escherichia coli BL21. The recombinant protein was purified and showed similar enzymatic properties to the native protein, exhibiting strong inhibitory activity against S. sclerotiorum. This shows that the ß-1,3-1,4-glucanase may play a very important role in B. subtilis Em7 biocontrol function. In addition, many physiochemical properties of the native and purified recombinant protein were compared, including the effect of pH, temperature, metal cations, substrate specificity, and kinetic parameters. All parameters were similar between the native and recombinant purified protein, indicating that the purified recombinant protein has potential for industrial applications.
Assuntos
Antifúngicos/farmacologia , Ascomicetos/efeitos dos fármacos , Bacillus subtilis/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/farmacologia , Proteínas Recombinantes , Proteínas de Bactérias/química , Proteínas de Bactérias/isolamento & purificação , Ativação Enzimática , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Cinética , Testes de Sensibilidade Microbiana , Estabilidade Proteica , Especificidade por SubstratoRESUMO
Apolipoprotein E (APOE) is recognized for its importance in lipoprotein metabolism and cardiovascular disease. We evaluated the association between APOE rs4420638 genotypes and circulating lipid concentrations along with the risk of coronary heart disease (CHD). We conducted a case-control study involving 1508 individuals to investigate the contribution of rs4420638 to the risk of CHD in Han Chinese. In addition, we performed a meta-analysis to evaluate the association between rs4420638 and CHD in Europeans and Asians. The results show that rs4420638 is significantly correlated with increased CHD risk in male Han Chinese [P = 0.040, odds ratio (OR) = 1.34, 95% confidential interval (95%CI) = 1.01-1.78] and is likely to increase the risk of CHD under the dominant model in males (P = 0.036, OR = 1.38, 95%CI = 1.02-1.88). A further subgroup analysis by rs4420638 genotype found a significant association of rs4420638 AA with high-density lipoprotein cholesterol (HDL-C) (P = 0.012) and APOA-I levels (P = 0.0001) in males. The meta-analysis suggests that rs4420638 significantly increases the risk of CHD (OR = 1.18, 95%CI = 1.14-1.22, P < 0.0001, fixed-effect method). Our case-control study shows that rs4420638 genotype AA has a significant association with the concentrations of circulating HDL-C and APOA-I in CHD in Han Chinese males. The meta-analysis suggests that rs4420638 is associated with CHD risk in Europeans and Asians.
Assuntos
Apolipoproteína A-I/sangue , Apolipoproteínas E/genética , HDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Polimorfismo Genético/genética , Idoso , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Sex hormones from environmental and physiological sources might play a major role in the pathogenesis of hepatoblastoma in children. This study investigated the effects of estradiol and bisphenol A on the proliferation and telomerase activity of human hepatoblastoma HepG2 cells. The cells were divided into 6 treatment groups: control, bisphenol A, estradiol, anti-estrogen ICI 182,780 (hereinafter ICI), bisphenol A+ICI, and estradiol+ICI. Cell proliferation was measured based on average absorbance using the Cell Counting-8 assay. The cell cycle distribution and apoptotic index were determined by flow cytometry. Telomerase activity was detected by polymerase chain reaction and a telomeric repeat amplification protocol assay. A higher cell density was observed in bisphenol A (P<0.01) and estradiol (P<0.05) groups compared with the control group. Cell numbers in S and G2/M phases after treatment for 48 h were higher (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h (P<0.05) were higher in these groups than in the control group. The cell density was also higher in bisphenol A+ICI (P<0.01) and estradiol+ICI (P<0.05) groups compared with the ICI group. Furthermore, cell numbers were increased in S and G2/M phases (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h were higher (P<0.05) in these groups than in the ICI group. Therefore, bisphenol A and estradiol promote HepG2 cell proliferation in vitro by inhibition of apoptosis and stimulation of telomerase activity via an estrogen receptor-dependent pathway.
Assuntos
Humanos , Compostos Benzidrílicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Estradiol/farmacologia , Antagonistas do Receptor de Estrogênio/farmacologia , Estrogênios não Esteroides/farmacologia , /efeitos dos fármacos , Fenóis/farmacologia , Telomerase/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estradiol/análogos & derivados , Citometria de Fluxo , /enzimologia , Interfase/efeitos dos fármacos , Telomerase/metabolismoRESUMO
The aim of this study was to optimize candidate antigen proteins for serological screening of Chlamydia trachomatis infection. C. trachomatis positive serum and swabs of genital secretions were collected from 50 patients in the Tianjin Medical University General Hospital, as well as from 30 patients negative for C. trachomatis. Samples were assessed by colloidal gold assay in a sexually transmitted disease clinic as follows: serum antibodies for eight kinds of C. trachomatis immunodominant proteins (Pgp3, CPAF, CT143, CT101, CT694, CT875, CT813, and IncA) were detected, and two traditional gold standards, immunofluorescence and C. trachomatis cell culture of genital secretions, were used for comparison in order to determine the antigen protein combinations with the highest sensitivity and specificity. Of the 50 samples that tested positive for C. trachomatis infection by colloidal gold assay, 44 tested positive by micro-immunofluorescence, whereas 6 tested negative. In contrast, 14 samples tested positive by cell culture, whereas 36 tested negative. Serological results of the immunodominant protein combination of Pgp3, CT694, and CT875 shared positive coincidence rates of 97.73 and 92.86% with C. trachomatis micro-immunofluorescence and cell culture, respectively. No antibodies of the three proteins were detected in the 30 C. trachomatis samples that tested negative by colloidal gold assay; these samples also tested negative in C. trachomatis genital secretion culture. Overall, the combination of the three immunodominant proteins Pgp3, CT694, and CT875 had good sensitivity and specificity for serological screening of C. trachomatis infection, and the process was simple and easy to apply.