RESUMEN

OBJECTIVES: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. RESULTS: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). CONCLUSIONS: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.

Asunto(s)

Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Papillomavirus Humano 16 , Proteínas Oncogénicas Virales/metabolismo , Infecciones por Papillomavirus/complicaciones , Proteínas Represoras/metabolismo , Macrófagos Asociados a Tumores/patología , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Diferenciación Celular , China/etnología , Técnicas de Cocultivo , Neoplasias Esofágicas/etnología , Neoplasias Esofágicas/virología , Carcinoma de Células Escamosas de Esófago/etnología , Carcinoma de Células Escamosas de Esófago/virología , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/etnología , Fenotipo , Receptores de Superficie Celular/metabolismo , Proteínas Represoras/genética , Microambiente Tumoral , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/virología

RESUMEN

The molecular mechanism of nasopharyngeal carcinoma (NPC) is poorly understood and effective therapeutic approaches are needed. This research aimed to excavate the attractor modules involved in the progression of NPC and provide further understanding of the underlying mechanism of NPC. Based on the gene expression data of NPC, two specific protein-protein interaction networks for NPC and control conditions were re-weighted using Pearson correlation coefficient. Then, a systematic tracking of candidate modules was conducted on the re-weighted networks via cliques algorithm, and a total of 19 and 38 modules were separately identified from NPC and control networks, respectively. Among them, 8 pairs of modules with similar gene composition were selected, and 2 attractor modules were identified via the attract method. Functional analysis indicated that these two attractor modules participate in one common bioprocess of cell division. Based on the strategy of integrating systemic module inference with the attract method, we successfully identified 2 attractor modules. These attractor modules might play important roles in the molecular pathogenesis of NPC via affecting the bioprocess of cell division in a conjunct way. Further research is needed to explore the correlations between cell division and NPC.

Asunto(s)

Carcinoma/genética , Regulación Neoplásica de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , Neoplasias Nasofaríngeas/genética , Perfilación de la Expresión Génica , Humanos , Carcinoma Nasofaríngeo , Mapeo de Interacción de Proteínas

RESUMEN

Carotenoids are important components of plant antioxidant systems, which protect photosystems from photooxidative destruction during ultraviolet-B (UV-B) exposure. The influence of carotenoids on total antioxidant capacity (TAC) of plants has rarely been studied. In this study, tobacco (Nicotiana tabacum L., 'K326') seedlings exposed to UV-B radiation were used in order to evaluate the effects of ambient levels of UV-B radiation on carotenoid accumulation. The aim was to investigate whether carotenoids could enhance TAC as a means of UV protection. Our results showed that leaf carotenoid content in the low UV-B exposure (+9.75 µW/cm2) plants was approximately 8% higher than that observed in control plants at 2-8 days of exposure. At high UV-B exposure (+20.76 µW/cm2), the carotenoid content increased rapidly after 1 day's exposure (10.41% higher than the control), followed by a return to the content as in control plants. Furthermore, carotenoid content positively correlated with TAC (P = 0.024). These results suggest that carotenoids have antioxidant properties and play an important role in the antioxidant system. UV-B exposure increased the carotenoid synthesis capability of plants. The plants could deplete the carotenoids to scavenge excess ROS at high UV-B radiation levels, which protects the tobacco plant from oxidative damage caused by UV-B stress.

Asunto(s)

Carotenoides/metabolismo , Nicotiana/metabolismo , Nicotiana/efectos de la radiación , Rayos Ultravioleta , Antioxidantes/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Plantones/metabolismo , Plantones/efectos de la radiación

RESUMEN

BACKGROUND: The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC. METHODS: 98 patients with GBC were recruited in this retrospective study. Using immunohistochemistry, we examined tumor-infiltrating CD3+ generic T-cells, CD8+ cytotoxic T-cells, CD45RO+ memory T-cells, and CD15+ neutrophils. Peripheral venous blood samples were also collected, and absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) were measured. The relationships between these variables and patient outcome were evaluated. RESULTS: Survival analysis revealed that the density of CD3+ cell infiltrates in the tumor microenvironment was positively correlated with overall survival (OS) and the density of CD15+ cell infiltrates was negatively correlated with the OS. The combined analysis showed that a high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates was an independent prognostic factor for GBC. In peripheral blood, survival analysis suggested that ANC and NLR were negatively correlated, while ALC was positively correlated with OS. Multivariate survival analysis showed that NLR was an independent prognostic factor for gallbladder cancer prognosis. CONCLUSIONS: The results indicate that the combination of high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates in tumor samples and pretreatment peripheral blood NLR were independent prognostic factors in patients with GBC.

Asunto(s)

Carcinoma de Células Escamosas/inmunología , Neoplasias de la Vesícula Biliar/inmunología , Inflamación/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Microambiente Tumoral/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/secundario , Femenino , Estudios de Seguimiento , Neoplasias de la Vesícula Biliar/sangre , Neoplasias de la Vesícula Biliar/patología , Humanos , Técnicas para Inmunoenzimas , Inflamación/sangre , Inflamación/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neutrófilos/inmunología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia

RESUMEN

Chronic obstructive pulmonary disease (COPD) is a devastating lung disorder characterized by sustained airway flow restriction that is not fully reversible. The precise pathogenic mechanisms are unknown, but it is clear that cigarette smoking and chronic inflammatory stimulation are the major causes of COPD. Lung inflammation associated with COPD involves multiple cytokines, aggregation, and activation of neutrophils in the airway and lung tissue, and release of proteases and oxygen free radicals. In this study, a rat model of COPD was established by daily cigarette smoke exposure plus endotoxin treatment (the experimental group). Respiratory curves were recorded by the BL-420 biological signal collecting and processing system. Furthermore, the contents of inflammatory mediators, intercellular adhesion molecular (ICAM)-1 and interleukin (IL)-1ß, in bronchoalveolar lavage fluid (BALF) were determined by enzyme linked immunosorbent assay for experimental, smoke-exposed only (control), and untreated (blank) rat groups. Protein expression levels of ICAM-1 and IL-1ß in the lung tissue were also compared among groups by the immunohistochemical streptavidin-peroxidase method. The COPD model rats exhibited severe dyspnea and lung inflammation as evidenced by significantly prolonged expiratory duration, higher respiratory rate, elevated ICAM-1 and IL-1ß in BALF, and higher ICAM-1 and IL-1ß protein expression in lung tissue compared to control and blank group rats. Chronic cigarette smoke exposure plus endotoxin is a feasible and reliable model of COPD that recapitulates many clinical signs and pathogenic responses. ICAM-1 and IL-1ß upregulation are possible early contributors to COPD-associated inflammatory lung injury.

Asunto(s)

Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1beta/metabolismo , Lesión Pulmonar/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Animales , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Interleucina-1beta/genética , Lesión Pulmonar/genética , Lesión Pulmonar/patología , Modelos Animales , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/patología , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba

RESUMEN

Recombinant human anti-tumor necrosis factor (TNF)-α scFv-Fc was expressed in TKO mutant Arabidopsis thaliana seeds using plant-specific codons. Immunoblotting using a human IgG1 antibody detected the expression of anti-TNF-α proteins in plants. Results from qRT-PCR analysis demonstrated that the time of harvest significantly affected the protein yield and quality. Our results indicate that the Phaseolus vulgaris ß-phaseolin promoter directed anti-TNF-α scFv-Fc expression in A. thaliana seeds, with a maximum yield obtained at 20-days of development. Although the yield of anti-TNF-α scFv-Fc protein was not very high, accumulation of recombinant proteins in seeds is an attractive and simple method that can be used to purify biologically active anti-TNF-α scFv-Fc.

Asunto(s)

Arabidopsis/genética , Fragmentos Fc de Inmunoglobulinas/genética , Semillas/metabolismo , Anticuerpos de Cadena Única/genética , Transgenes , Factor de Necrosis Tumoral alfa/inmunología , Arabidopsis/metabolismo , Fragmentos Fc de Inmunoglobulinas/inmunología , Fragmentos Fc de Inmunoglobulinas/metabolismo , Proteínas Recombinantes , Semillas/genética , Anticuerpos de Cadena Única/inmunología , Anticuerpos de Cadena Única/metabolismo

RESUMEN

Desmoglein 4 (DSG4) has an important role in the development of wool traits in domestic animals. The full-length DSG4 gene, which contains 3918 bp, a complete open-reading-frame, and encodes a 1040-amino acid protein, was amplified from Liaoning cashmere goat. The sequence was compared with that of DSG4 from other animals and the results show that the DSG4 coding region is consistent with interspecies conservation. Thirteen single-nucleotide polymorphisms (SNPs) were identified in a highly variable region of DSG4, and one SNP (M-1, G>T) was significantly correlated with white and black coat color in goat. Haplotype distribution of the highly variable region of DSG4 was assessed in 179 individuals from seven goat breeds to investigate its association with coat color and its differentiation among populations. However, the lack of a signature result indicates DGS4 haplotypes related with the color of goat coat.

Asunto(s)

Desmogleínas/genética , Cabras/metabolismo , Color del Cabello/genética , Polimorfismo de Nucleótido Simple , Animales , Cabras/genética , Haplotipos , Filogenia , Análisis de Secuencia de ARN

RESUMEN

The aim of this study was to investigate the effects of dendritic cell (DC) therapy in osteosarcoma. Bone marrow DCs from Wistar (allograft group) and Sprague Dawley (SD) (homograft group) rats were electrically fused with the SD-derived osteosarcoma cell line UMR106 to generate a DC-osteosarcoma fusion (DOF) tumor vaccine, which was co-incubated with SD T lymphocytes to stimulate T cell proliferation. CD8+ and CD4+ cell percentages were measured by flow cytometry; tumor-cytotoxic effects of cytotoxic T lymphocytes (CTLs) were measured by the MTT assay. Active immunotherapy was applied to SD osteosarcoma model rats via subcutaneous injection of the tumor vaccine. Significant potentiation of T lymphocyte proliferation was observed in both groups. In the homograft group, the CD8+/CD4+ ratio was elevated to 78.2 from 55.1% after stimulation (P < 0.05) whereas the CD4+ cell percentage was reduced from 61.3 to 21.2% (P < 0.05). Similarly, in the allograft group the CD8+ and CD4+ cell percentages significantly increased (33.8 to 69.6%) or decreased (61.3 to 28.1%) after stimulation, respectively (P < 0.05). The preferential homograft group response was not significant (P > 0.05). Induced UMR106- specific CTLs showed a significantly higher tumor-cytotoxic effect after stimulation (P < 0.05). After DOF active immunotherapy, tumor bodies displayed atrophy or disappearance, leading to higher survival times and rates (60 and 70% in the allograft and homograft groups) (P < 0.05). This study demonstrated that osteosarcoma immunotherapy using a DC-fused tumor vaccine can effectively stimulate T lymphocyte proliferation and induce the tumor-cytotoxic activity of CTLs.

Asunto(s)

Neoplasias Óseas/terapia , Linfocitos T CD4-Positivos/inmunología , Vacunas contra el Cáncer/farmacología , Células Dendríticas/inmunología , Osteosarcoma/terapia , Linfocitos T Citotóxicos/inmunología , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Neoplasias Óseas/inmunología , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/trasplante , Fusión Celular , Línea Celular Tumoral , Proliferación Celular , Técnicas de Cocultivo , Citotoxicidad Inmunológica , Células Dendríticas/citología , Células Dendríticas/trasplante , Inmunoterapia/métodos , Activación de Linfocitos , Recuento de Linfocitos , Masculino , Osteosarcoma/inmunología , Osteosarcoma/mortalidad , Osteosarcoma/patología , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Análisis de Supervivencia , Linfocitos T Citotóxicos/citología , Trasplante Homólogo , Resultado del Tratamiento

RESUMEN

The ZmDULL1 gene encodes a starch synthase and is a determinant of the structure of endosperm starch in maize (Zea mays L.). However, little is known regarding the regulatory mechanism of the ZmDULL1 gene. In this study, we isolated and characterized the ZmDULL1 promoter (PDULL1), which is the 5' flanking region of ZmDULL1 in maize. Sequence analysis showed that several cis-acting elements important for endosperm expression (GCN4_motif and AACA-element) were located within the promoter. A series of PDULL1 deletion derivatives, PDULL1-1-PDULL1-4, from the translation start code (-1676, -1216, -740, and -343) were fused to the ß-glucuronidase (GUS) reporter gene. Each deletion construct was transformed into rice using the Agrobacterium-mediated method, and then GUS activity was measured in transgenic plants. The results showed that PDULL1 was an endosperm-specific promoter. Further analysis showed that the promoter sequence (-343 to -1 base pairs) was sufficient for mediating GUS gene expression in endosperm. These results indicate that the region from -343 to -1 base pairs of PDULL1 is valuable for transgenic rice breeding and genetic engineering studies.

Asunto(s)

Endospermo/genética , Secuencias Reguladoras de Ácidos Nucleicos/genética , Almidón Sintasa/genética , Zea mays/enzimología , Clonación Molecular , Endospermo/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Genes Reporteros , Glucuronidasa/biosíntesis , Glucuronidasa/genética , Glútenes/metabolismo , Oryza/genética , Oryza/crecimiento & desarrollo , Plantas Modificadas Genéticamente/enzimología , Plantas Modificadas Genéticamente/genética , Regiones Promotoras Genéticas , Almidón/metabolismo , Almidón Sintasa/biosíntesis , Zea mays/genética

RESUMEN

PURPOSE: Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were immune response-related indicators. Preoperative NLR and PLR had been considered to be related to the prognosis of various cancers. The objective of this study was to evaluate the prognostic significance of NLR and PLR in patients with gallbladder carcinoma (GBC). METHODS: From 2001 to 2013, 145 patients with GBC were recruited in this retrospective study. Cutoff values of NLR and PLR were determined by receiver operating characteristic curves (ROC). The correlation of clinical data, including tumor differentiation, nevin stage, TNM stage, operation margin, operation mode, NLR, PLR, hemoglobin, C reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 199 (CA199) with median survival period of patients was analyzed by univariate survival analysis. The multivariate prognosis analysis was performed to select the independent prognostic factors. RESULTS: The cutoff values of NLR and PLR were 1.94 and 113.34, respectively. Compared with low NLR and low PLR group, the 5-year survival rates in high NLR and high PLR group were reduced (P < 0.05). The degree of tumor differentiation, nevin stage, TNM stage, operation mode, NLR, PLR, CA199, total bilirubin, CRP and CEA were associated with the median survival period of patients (P < 0.01). The multivariate prognosis analysis showed that NLR, nevin stage, operation mode and hemoglobin were independent prognostic factors (P < 0.05). CONCLUSION: Preoperative NLR and PLR were closely related to prognosis of patients with GBC and might be useful for the evaluation of prognosis of patients with GBC.

Asunto(s)

Adenocarcinoma/sangre , Plaquetas , Carcinoma Adenoescamoso/sangre , Carcinoma de Células Escamosas/sangre , Neoplasias de la Vesícula Biliar/sangre , Linfocitos , Neutrófilos , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Proteína C-Reactiva/metabolismo , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Carcinoma Adenoescamoso/patología , Carcinoma Adenoescamoso/cirugía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Recuento de Plaquetas , Periodo Preoperatorio , Pronóstico , Curva ROC , Estudios Retrospectivos , Análisis de Supervivencia

RESUMEN

Hepatocyte growth factor (HGF) is a protective factor in myocardial injury, but its mechanisms of action have not yet been fully elucidated. Nexilin, which locates specifically to the Z-disc, is a novel Z-disc protein that enables the Z-discs to persistently withstand the extreme mechanical forces generated during muscle contraction. Therefore, we investigated the role of HGF in modulating nexilin expression in hypoxia-reoxygenation (H/R)-treated cardiomyocytes. We cultured neonatal cardiomyocytes and treated them with HGF. The mRNA and protein levels of nexilin were determined by RT-PCR and Western blotting. H/R treatment decreased nexilin mRNA expression and nexilin protein levels in cardiomyocytes. Furthermore, treatment with HGF upregulated nexilin expression and the JNK inhibitor SP600125 partly inhibited HGF-induced nexilin upregulation. In conclusion, our results suggest that ischemia-reperfusion injury may downregulate nexilin expression in cardiomyocytes, and HGF may exert its protective role during myocardial ischemic injury through upregulation of nexilin expression in cardiomyocytes.

Asunto(s)

Factor de Crecimiento de Hepatocito/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Proteínas de Microfilamentos/genética , Miocitos Cardíacos/efectos de los fármacos , Oxígeno/farmacología , ARN Mensajero/genética , Animales , Animales Recién Nacidos , Antracenos/farmacología , Butadienos/farmacología , Hipoxia de la Célula , Flavonoides/farmacología , Regulación de la Expresión Génica , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas de Microfilamentos/agonistas , Proteínas de Microfilamentos/antagonistas & inhibidores , Proteínas de Microfilamentos/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Nitrilos/farmacología , Cultivo Primario de Células , Inhibidores de Proteínas Quinasas/farmacología , ARN Mensajero/metabolismo , Ratas , Transducción de Señal

RESUMEN

The interaction between neutron-rich nuclei plays an important role for understanding the reaction mechanism of the fusion process as well as for the energy production through pycnonuclear reactions in the crust of neutron stars. We have performed the first measurements of the total fusion cross sections in the systems (10,14,15)C+(12)C using a new active target-detector system. In the energy region accessible with existing radioactive beams, a good agreement between the experimental and theoretical cross sections is observed. This gives confidence in our ability to calculate fusion cross sections for systems which are outside the range of today's radioactive beam facilities.

RESUMEN

To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

Asunto(s)

Minería de Datos , Redes Reguladoras de Genes , Transducción de Señal/genética , Neoplasias Gástricas/genética , Secuencias de Aminoácidos/genética , Carcinogénesis/genética , Muerte Celular , Retroalimentación Fisiológica , Regulación de la Expresión Génica , Ontología de Genes , Humanos , Anotación de Secuencia Molecular , Fosforilación , Neoplasias Gástricas/metabolismo

RESUMEN

To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

Asunto(s)

Humanos , Minería de Datos , Redes Reguladoras de Genes , Transducción de Señal/genética , Neoplasias Gástricas/genética , Secuencias de Aminoácidos/genética , Muerte Celular , Carcinogénesis/genética , Retroalimentación Fisiológica , Regulación de la Expresión Génica , Ontología de Genes , Anotación de Secuencia Molecular , Fosforilación , Neoplasias Gástricas/metabolismo

RESUMEN

Laryngeal carcinoma is a common tumor of the head and neck region. This study aimed to examine the outcomes of laryngectomy in elderly patients with laryngeal carcinoma. One-hundred twenty-two patients (male, 117; female, 5) aged 60 years or older (range, 60-94 years) who underwent laryngectomy between 1996 and 2010 were included. All patients were diagnosed with squamous cell carcinoma of the larynx, and 95 patients (77.9%) had additional concurrent diseases. Tumors were staged according to the TNM categories of the American Joint Committee on Cancer 2002 criteria; there were 16 stage-I, 24 stage-II, 52 stage-III, and 30 stage-IV cases. With regard to treatment modalities, 10 patients underwent transoral laser laryngectomy, 25 underwent partial laryngectomy, and 87 underwent total laryngectomy. When necessary, neck dissection was performed according to the Dalian criteria set in 2004 (a Chinese standard). Of the 122 cases, there were 114 cases of grade I (93.4%), 5 cases of grade II, and 3 cases of grade III (pharyngeal fistula in 2 cases recovered after 2 weeks of care) wound healing. No significant differences were observed in the occurrence or severity of comorbidities. The 1-, 3-, and 5-year actuarial survival rates were 97.5% (119/122), 84.4% (92/109), and 68.4% (67/98), respectively. Age alone should not be used to determine treatment options for elderly patients with squamous cell carcinoma. Presuming that careful pre-treatment evaluations are performed, laryngectomy is a key method for elderly patients with laryngeal carcinoma.

Asunto(s)

Carcinoma de Células Escamosas/cirugía , Neoplasias Laríngeas/cirugía , Laringectomía , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Neoplasias Laríngeas/epidemiología , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento

RESUMEN

Authenticating multi-species original raw materials in commercial formulations is difficult. Jin Yin Hua and Shan Yin Hua, both classified as raw honeysuckle materials in the Chinese Pharmacopoeia, are used in various medicines. Differentiating one variety from another is difficult based on chemical analysis. We developed molecular authentication of multi-species original honeysuckle in 3 brands of commercial tablets using allele-specific PCR. All 3 tablets contained both Jin Yin Hua and Shan Yin Hua. We also built a PCR-enzyme digestion method and enzymatic mutation detection in the PCR fragments of psbA-trnH and trnL-trnF, and the restriction endonucleases HinfI and NlaIV, respectively. The PCR-enzyme digestion method produced the same result as the allele-specific PCR. Sequence and phylogenetic analyses show that the tablets YXC and YQJ contained Lonicera japonica and L. macranthoides as original raw materials, and LYG contained L. japonica, L. hypoglauca, and L. macranthoides.

Asunto(s)

Lonicera/clasificación , Lonicera/genética , Medicina Tradicional China/normas , Alelos , Biología Computacional , ADN de Plantas , Filogenia , Polimorfismo de Nucleótido Simple

RESUMEN

Keshan disease (KD) is an endemic cardiomyopathy associated with selenium deficiency. Recent studies indicate that glutathione peroxidase 1 (GPx1) mutation decreases GPx activity in myocardial cells and increases the risk of KD. To further clarify the correlation between GPx1 polymorphism and KD, we analyzed GPx1 polymorphism, blood selenium levels and GPx activity in KD patients and healthy controls in Heilongjiang Province. Four and 24 new mutation loci in the promoter and the exon region, respectively, of the GPx1 gene were found in the subjects, in contrast with the previously reported loci. There were no significant differences in the mutation frequency of these loci between the KD group and controls (chi-square test; P > 0.05). However, the mutation frequency of exon 474 was higher in the KD group (7/36) than in controls (2/41), and GPx activity was lower in the mutation group (90.475 ± 23.757 U/L) than in the non-mutation group (93.947 ± 17.463 U/L). Further investigation is necessary to clarify a possible causality between GPx1 exon 474 mutation and KD.

Asunto(s)

Cardiomiopatías/genética , Infecciones por Enterovirus/genética , Glutatión Peroxidasa/genética , Miocitos Cardíacos/enzimología , Polimorfismo Genético , Selenio/deficiencia , Cardiomiopatías/sangre , Cardiomiopatías/enzimología , Estudios de Casos y Controles , China , Infecciones por Enterovirus/sangre , Infecciones por Enterovirus/enzimología , Exones , Femenino , Estudios de Asociación Genética , Genotipo , Glutatión Peroxidasa/metabolismo , Humanos , Masculino , Tasa de Mutación , Miocitos Cardíacos/patología , Regiones Promotoras Genéticas , Selenio/sangre , Glutatión Peroxidasa GPX1

RESUMEN

We identified a disease-causing mutation of the RUNX2 gene in a four-generation Chinese family affected with cleidocranial dysplasia (CCD). For mutation analysis, the coding region of RUNX2 was sequenced with DNA from two patients and three unaffected family members. The RUNX2 mutation was investigated in 50 normal controls by denaturing high pressure liquid chromatography. A heterozygous single-base deletion (c.549delC) of RUNX2, which predicts a termination site at the 185th codon and leads to a stop in the runt domain of RUNX2 protein, was detected in both patients but not in the three unaffected members of the family. This mutation was also not found in 50 controls and has not been reported previously. We demonstrated that a novel mutation (c.549delC) of RUNX2 is associated with CCD in a Chinese family, adding to the repertoire of RUNX2 mutations related to CCD.

Asunto(s)

Pueblo Asiatico/genética , Displasia Cleidocraneal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Eliminación de Secuencia/genética , Adolescente , Secuencia de Aminoácidos , Secuencia de Bases , China , Displasia Cleidocraneal/diagnóstico por imagen , Subunidad alfa 1 del Factor de Unión al Sitio Principal/química , Análisis Mutacional de ADN , Familia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Fenotipo , Radiografía

Asunto(s)

Accesibilidad a los Servicios de Salud , Adolescente , China/epidemiología , Distribución por Edad , Distribución por Sexo , Estudios Retrospectivos , Factores Socioeconómicos , Factores de Tiempo , Etnicidad , Lepra/diagnóstico , Lepra/epidemiología , Lepra/prevención & control , Encuestas Epidemiológicas

RESUMEN

Maize streak virus (MSV) disease may cause significant grain yield reductions in maize in Africa. Réunion island maize germplasm is a proven source of strong resistance. Its genetic control was investigated using 123 RFLP markers in an F(2) population of D211 (resistant) × B73 (susceptible). This population of 165 F(2:3) families was carefully evaluated in Harare (Zimbabwe) and in Réunion. Artificial infestation was done with viruliferous leafhoppers. Each plant was rated weekly six times after infestation on a 1-9 scale previously adjusted by image analysis. QTL analyses were conducted for each scoring date, and for the areas under the disease, incidence and severity progress curves. The composite interval mapping method used allowed the estimation of the additive and dominance effects and QTL × environment interactions. Heritabilities ranged from 73% to 98%, increasing with time after infestation. Resistance to streak virus in D211 was provided by one region on chromosome 1, with a major effect, and four other regions on chromosomes 2, 3 (two regions) and 10, with moderate or minor effects. Overall, they explained 48-62% of the phenotypic variation for the different variables. On chromosome 3, one of the two regions seemed to be more involved in early resistance, whereas the second was detected at the latest scoring date. Other QTLs were found to be stable over time and across environments. Mild QTL × environment interactions were detected. Global gene action appeared to be partially dominant, in favor of resistance, except at the earliest scoring dates, where it was additive. From this population, 32 families were chosen, representing the whole range of susceptibility to MSV. They were tested in Réunion against three MSV clones, along with a co-inoculation of two of them. Virulence differences between clones were significant. There were genotype × clone interactions, and these were more marked for disease incidence than for severity. Although these interactions were not significant for the mean disease scores, it is suggested that breeders should select for completely resistant genotypes.