RESUMEN
PURPOSE: The current study aims to explore the effects of CDKN2A on cell proliferation and cycle, and investigate the underlying mechanisms. METHODS: Expression of CDKN2A in cervical cancer cell lines was evaluated by real-time quantitative PCR (RT-qPCR) and western blotting. Apoptotic rate was detected by Annexin V assay. MTT assay, Transwell assay and cell cycle assay kit were applied to examine the effect of CDKN2A on cell viability, invasion and cell cycle. Co-immunoprecipitation and western blotting were devoted to explore the mechanism by which CDKN2A contributes to cell function. RESULTS: CDKN2A was expressed at a low level in cervical cancer cell lines. Overexpression of CDKN2A inhibited cell proliferation and invasion, and caused cell cycle arrest in the G1 phase. CDKN2A mediates the AKT-mTOR signaling pathway by suppressing lactate dehydrogenase (LDHA). Taken together, our data revealed that CDKN2A can be applied as a therapeutic target for the treatment of cervical cancer in future. CONCLUSIONS: CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT-mTOR pathway.
Asunto(s)
Proliferación Celular/fisiología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Apoptosis/fisiología , Línea Celular Tumoral , Supervivencia Celular/fisiología , Regulación hacia Abajo/fisiología , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular , Células HeLa , Humanos , Inmunoprecipitación , Invasividad Neoplásica , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: We conduct this study to compare the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) concurrent weekly nedaplatin (NDP) versus IMRT alone in the stage III/IV non-surgical elderly patients with non-small-cell lung cancer (NSCLC). METHODS: 117 patients were enrolled into our study. The patients were assigned into two different groups: radiotherapy (RT) group and chemoradiotherapy (CRT) group. Patients in RT group were treated with IMRT at a single daily dose of 2 Gy for 5 days per week, totally 52-66 Gy. The CRT group, IMRT concurrent weekly NDP at a dose of 25 mg/m2. RESULTS: In CRT group, the median survival was 11.0 months (95% confidence interval [CI], 8.894-13.106 months) and in RT group, it was 7.0 months (95% CI 5.771-8.229 months). The 1-year, 2-year, 3-year, survival rates in the combined treatment arm were higher than the radiation therapy arm (46.8 vs 25.9%, 25.1 vs 11.8%, 14.7 vs 8.0%; p < 0.001). The Cox's multiple regression analysis showed that CRT had significantly better overall survival than RT (HR 0.523; 95.0% CI 0.338-0.807; p = 0.003). The objective response rate provided that 73.3% treated with CRT compared with 51.1% (p = 0.018) received RT alone. Of the hematologic toxicities, leukocytes (35.0 vs 0%; p < 0.001), neutrophils (33.3 vs 0%; p < 0.001) were significantly more common in the CRT group than the RT group. CONCLUSIONS: We first discovered that NDP concurrent IMRT for treating stage III/IV non-surgical elderly patients with NSCLC was good curative effect of better objective response rate and well-tolerated. However, within the low number of patients, only stage IV gained a survival benefit.
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Antineoplásicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia/métodos , Neoplasias Pulmonares/terapia , Compuestos Organoplatinos/administración & dosificación , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodosRESUMEN
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignant disease worldwide, especially in China. We aimed to determine the level of autoantibodies against L1CAM in patients with ESCC. METHODS: Levels of circulating autoantibodies against L1CAM antigens were determined by an enzyme-linked immunosorbent assay in cohort 1 (191 patients with ESCC and 94 normal controls) and validated in cohort 2 (47 patients with ESCC and 47 normal controls). Receiver-operating characteristics were employed to calculate diagnostic accuracy. Cumulative survival time was calculated by the Kaplan-Meier method and analyzed by the log-rank test. RESULTS: In cohorts 1 and 2, levels of autoantibodies against L1CAM were all significantly higher in sera of patients with ESCC compared to normal controls (P < 0.05). Detection of autoantibodies against L1CAM provided a sensitivity of 26.2%, a specificity of 90.4%, and an area under the curve (AUC) of 0.603 (95% CI 0.535-0.672) in diagnosing ESCC in cohort 1, and a sensitivity of 27.7%, a specificity of 91.5%, and an AUC of 0.628 (95% CI 0.516-0.741). Similar results were observed in the diagnosis of early stage ESCC (25.2% sensitivity, 90.4% specificity, and an AUC of 0.611 (95% CI 0.533-0.689) in cohort 1, and 33.3% sensitivity, 91.5% specificity, and an AUC of 0.636 (95% CI 0.439-0.832) in cohort 2). Moreover, positive rates of autoantibodies against L1CAM had no statistical correlation with clinical outcome of ESCC (P > 0.05). CONCLUSIONS: Our results suggest that circulating autoantibodies against L1CAM is a potential biomarker for the early detection of ESCC.
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Autoanticuerpos/sangre , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Neoplasias Esofágicas/sangre , Molécula L1 de Adhesión de Célula Nerviosa/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/terapia , Estudios de Casos y Controles , Terapia Combinada , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Curva ROC , Tasa de SupervivenciaRESUMEN
The tumor necrosis factor-alpha (TNF-α) G-308A polymorphism has been suggested to be a susceptibility factor for myocardial infarction (MI). However, differing results from various studies have led to controversial conclusions. Hence, we performed a meta-analysis to evaluate the association between TNF-α G-308A polymorphism and MI. Reported studies published before March 30, 2015 were included and analyzed from the PubMed and Embase databases. Study selection and data extraction were carried out independently by two authors. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association between the selected variables using the Comprehensive Meta-Analysis v2.2 software. In total, 12 publications with 13 case-control studies consisting of 6037 cases and 7262 controls were included in our meta-analysis. The overall results showed that there was no significant association between TNF-α G-308A polymorphism and MI risk [A vs G: OR = 1.18, 95%CI = 0.94-1.48; AA vs GG: OR = 1.23, 95%CI = 0.74-2.05; GA vs GG: OR = 1.22, 95%CI = 0.98-1.51; (GA+AA) vs G: OR = 1.21, 95%CI = 0.96-1.54; AA vs (GG+GA): OR = 1.16, 95%CI = 0.72-1.88]. However, when subgroup analysis was performed according to the stages of MI, results indicated that there was a significant association between TNF-α G-308A polymorphism and the risk of acute MI. Other subgroup analyses revealed no significant associations. Current evidence suggests that TNF-α G-308A polymorphism may be associated with increased risk for acute MI.
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Predisposición Genética a la Enfermedad , Infarto del Miocardio/genética , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/genética , Estudios de Casos y Controles , Expresión Génica , Humanos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/patología , Oportunidad Relativa , Factores de RiesgoRESUMEN
Members of the archaeal phylum Bathyarchaeota are widespread and abundant in the energy-deficient marine subsurface sediments. However, their life strategies have remained largely elusive. Here, we provide genetic evidence that some lineages of Bathyarchaeota are acetogens, being capable of homoacetogenesis, a metabolism so far restricted to the domain Bacteria. Metabolic reconstruction based on genomic bins assembled from the metagenome of deep-sea subsurface sediments shows that the metabolism of some lineages of Bathyarchaeota is similar to that of bona fide bacterial homoacetogens, by having pathways for acetogenesis and for the fermentative utilization of a variety of organic substrates. Heterologous expression and activity assay of the acetate kinase gene ack from Bathyarchaeota, demonstrate further the capability of these Bathyarchaeota to grow as acetogens. The presence and expression of bathyarchaeotal genes indicative of active acetogenesis was also confirmed in Peru Margin subsurface sediments where Bathyarchaeota are abundant. The analyses reveal that this ubiquitous and abundant subsurface archaeal group has adopted a versatile life strategy to make a living under energy-limiting conditions. These findings further expand the metabolic potential of Archaea and argue for a revision of the role of Archaea in the carbon cycle of marine sediments.
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Acetatos/metabolismo , Archaea/enzimología , Archaea/genética , Sedimentos Geológicos/microbiología , Metagenoma , Agua de Mar/microbiología , Acetato Quinasa/genética , Archaea/clasificación , Archaea/metabolismo , Ciclo del Carbono , ADN de Archaea , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Oxidación-Reducción , Perú , Filogenia , ARN Ribosómico 16S , Sulfatos/metabolismoRESUMEN
The Anyi tile-like gray chicken is a Chinese indigenous breed with a gray dilution phenotype, having gray feathers, comb, skin, shanks, and beak, which is valuable for genetic research on pigmentation. However, the genetic basis of the gray dilution phenotype remains unknown. The objective of this study was to investigate the genetic basis of the gray dilution phenotype in the Anyi tile-like gray chicken. We found that all Anyi tile-like gray chickens tested in this study carried at least one E allele, which is responsible for the appearance of black feathers, and some of them carried the FM allele, which is responsible for the black skin phenotype. A single nucleotide polymorphism (C.1909A>G) was identified within the melanophilin (MLPH) gene and was significantly associated with the gray dilution phenotype. Our findings suggest that the E and FM alleles act together to cause the development of the "five-black" phenotype (black feather, comb, skin, shank, and beak), whereas the MLPH mutation results in defective melanosome transport, leading to the development of the "five-gray" phenotype.
Asunto(s)
Mutación , Fenotipo , Receptor de Melanocortina Tipo 1/genética , Pigmentación de la Piel/genética , Animales , Pollos , Plumas/metabolismo , Polimorfismo de Nucleótido SimpleRESUMEN
The effect of weaning age on the adrenal cortex, which plays a vital role in the stress response, is currently unknown. Therefore, plasma adrenocorticotropic hormone (ACTH) and cortisol levels, weights and relative weights of adrenal glands, and steroidogenesis-related protein and enzyme expression levels in piglets weaned on different days were determined. Piglets weaned at 35 days had significantly lower ACTH levels than those weaned at 14 or 21 days, and cortisol levels of piglets weaned at 21, 28, and 35 days were significantly lower than those of piglets weaned on day 14. Adrenal gland weights of piglets weaned at 28 and 35 days and relative adrenal gland weights of piglets weaned at 35 days were significantly lower than those of piglets weaned at 14 days. However, no significant difference was detected in the expression of melanocortin-type 2 receptor mRNA, which is associated with weaning age. Steroidogenic acute-regulatory (StAR) mRNA and cholesterol side-chain cleavage cytochrome P450 mRNA expression levels in piglets weaned at 28 and 35 days were significantly lower than in those weaned at 14 or 21 days, and P450 11ß mRNA expression levels in piglets weaned at 28 and 35 days were significantly lower than in those weaned at 14 days. Therefore, early-weaned piglets exhibited increased adrenal gland weights and StAR and steroidogenic enzyme expression, all of which contributed to high cortisol levels. The high plasma ACTH and cortisol levels in early-weaned piglets indicate that these animals would be greatly affected by stress.
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Hidrocortisona/sangre , Destete , Glándulas Suprarrenales/crecimiento & desarrollo , Glándulas Suprarrenales/metabolismo , Hormona Adrenocorticotrópica/sangre , Animales , Familia 2 del Citocromo P450/genética , Familia 2 del Citocromo P450/metabolismo , Femenino , Masculino , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Receptor de Melanocortina Tipo 2/genética , Receptor de Melanocortina Tipo 2/metabolismo , PorcinosRESUMEN
This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China. This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 ± 10 years]; 482 men and 32 women in the control group [mean age, 53 ± 10 years]) with confirmed COPD or at risk for COPD. Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly. Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD. Control group patients received usual care. The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD. COPD incidence was lower in the intervention group than in the control group (10% vs 16%, <0.05). A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients. The intervention group showed significant improvement in smoking cessation compared with the control group, and smokers in the intervention group had lower smoking indices than in the control group (350 vs 450, <0.05). The intervention group also had a significantly lower cumulative COPD-related death rate than the control group (37% vs 47%, <0.05). A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk, delaying a decline in lung function in COPD patients and those at risk, and reducing mortality of COPD.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/prevención & control , Población Rural , Cese del Hábito de Fumar/estadística & datos numéricos , Análisis por Conglomerados , China/epidemiología , Personal de Salud/educación , Incidencia , Estilo de Vida , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Gestión de Riesgos , Espirometría , Factores de TiempoRESUMEN
Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL)-1β and transforming growth factor (TGF)-β levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12±10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81±10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P<0.01) and significantly higher plasma TGF-β levels (P=0.002), whereas there was no difference in plasma IL-1β levels between the two groups. Moreover, plasma MFG-E8 levels decreased progressively between Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and GOLD IV stage COPD. Multiple regression analysis showed that the forced expiratory volume in 1 s (FEV1 % predicted) and smoking habit were powerful predictors of MFG-E8 in COPD (P<0.01 and P=0.026, respectively). MFG-E8 was positively associated with the FEV1 % predicted and negatively associated with smoking habit. The area under the receiver operating characteristic curve was 0.874 (95% confidence interval: 0.798-0.95; P<0.01). Our findings demonstrated the utility of MFG-E8 as a marker of disease severity in COPD and that cigarette smoke impaired MFG-E8 expression in these patients.
Asunto(s)
Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antígenos de Superficie/sangre , Apoptosis/fisiología , Proteínas de la Leche/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Volumen Espiratorio Forzado , Interleucina-1beta/sangre , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Análisis de Regresión , Curva ROC , Índice de Severidad de la Enfermedad , Fumar/sangre , Factor de Crecimiento Transformador beta/sangreRESUMEN
Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL)-1ß and transforming growth factor (TGF)-ß levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12±10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81±10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P<0.01) and significantly higher plasma TGF-ß levels (P=0.002), whereas there was no difference in plasma IL-1ß levels between the two groups. Moreover, plasma MFG-E8 levels decreased progressively between Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and GOLD IV stage COPD. Multiple regression analysis showed that the forced expiratory volume in 1 s (FEV1 % predicted) and smoking habit were powerful predictors of MFG-E8 in COPD (P<0.01 and P=0.026, respectively). MFG-E8 was positively associated with the FEV1 % predicted and negatively associated with smoking habit. The area under the receiver operating characteristic curve was 0.874 (95% confidence interval: 0.798-0.95; P<0.01). Our findings demonstrated the utility of MFG-E8 as a marker of disease severity in COPD and that cigarette smoke impaired MFG-E8 expression in these patients.
Asunto(s)
Antígenos de Superficie/sangre , Apoptosis/fisiología , Proteínas de la Leche/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Factores de Confusión Epidemiológicos , Ensayo de Inmunoadsorción Enzimática , Femenino , Volumen Espiratorio Forzado , Humanos , Interleucina-1beta/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Curva ROC , Análisis de Regresión , Índice de Severidad de la Enfermedad , Fumar/sangre , Factor de Crecimiento Transformador beta/sangreRESUMEN
This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China. This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 ± 10 years]; 482 men and 32 women in the control group [mean age, 53 ± 10 years]) with confirmed COPD or at risk for COPD. Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly. Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD. Control group patients received usual care. The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD. COPD incidence was lower in the intervention group than in the control group (10% vs 16%, <0.05). A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients. The intervention group showed significant improvement in smoking cessation compared with the control group, and smokers in the intervention group had lower smoking indices than in the control group (350 vs 450, <0.05). The intervention group also had a significantly lower cumulative COPD-related death rate than the control group (37% vs 47%, <0.05). A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk, delaying a decline in lung function in COPD patients and those at risk, and reducing mortality of COPD.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/prevención & control , Población Rural , Cese del Hábito de Fumar/estadística & datos numéricos , Adulto , China/epidemiología , Análisis por Conglomerados , Femenino , Personal de Salud/educación , Humanos , Incidencia , Estilo de Vida , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Gestión de Riesgos , Espirometría , Factores de TiempoRESUMEN
DDX6 belongs to a family of DEAD-box RNA helicases, which are RNA splicing proteins that ensure the correct folding and structure of mature RNA. Gametogenesis requires the participation of many kinds of RNA. To explore its functions during Eriocheir sinensis gametogenesis, we cloned a full-length DDX6 cDNA sequence from E. sinensis (Es-DDX6) which contains a 1536-nucleotide open reading frame encoding a 512-amino acid protein. Multiple sequence alignments showed that Es-DDX6 has ten conservative DEAD-box family motifs. Tissue expression analysis of Es-DDX6 mRNA and protein levels showed that Es-DDX6 was highly expressed in both the ovary and testis. qRT-PCR analysis revealed the widespread expression of Es-DDX6 mRNA during various stages of gonad development peaking in October. In addition, immunohistochemical studies showed that oocytes and the spermatogonium and primary spermatocytes of testes contained high levels of cytoplasmic Es-DDX6 and decreased expression levels in spermatids. Interestingly, there was no expression of Es-DDX6 in these cells as they matured along the male reproductive system. Since oocytes and spermatocytes are active in meiosis and oocytes undergo rapid growth in October, these results provide preliminary evidence that Es-DDX6 plays a role in E. sinensis gametogenesis and oocyte growth processes.
Asunto(s)
Braquiuros/genética , ARN Helicasas DEAD-box/genética , Gametogénesis , Secuencia de Aminoácidos , Animales , Braquiuros/metabolismo , Clonación Molecular , ARN Helicasas DEAD-box/metabolismo , Evolución Molecular , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Masculino , Datos de Secuencia Molecular , Especificidad de Órganos , Ovario/metabolismo , Alineación de Secuencia , Testículo/metabolismoRESUMEN
We examined the value of serum procalcitonin (PCT), C-reactive protein (CRP), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for predicting the survival of patients with early-onset stroke associated pneumonia (EOP). A total of 207 stroke patients were enrolled, and 91 developed EOP. Upon admission, serum PCT, CRP, sTREM-1 levels, clinical pulmonary infection score, and Acute Physiology and Chronic Health Evaluation II score were all significantly higher in patients with EOP than in those without EOP (P < 0.05). Of the 91 patients who developed EOP, 39 (42.9%) died (non-survivors) within 28 days. The Acute Physiology and Chronic Health Evaluation II score on admission was significantly higher in non-survivors than in survivors (P < 0.05). Serum PCT and sTREM-1 levels were slightly elevated on days 1, 3, and 5 in non-survivors and gradually decreased in survivors. Serum PCT, sTREM-1, and CRP levels were all significantly higher in non-survivors than in survivors on days 1, 3, and 5 (P < 0.05). The sensitivity and specificity of PCT for predicting the outcome of EOP were 84.6 and 71.2%, the sensitivity and specificity of sTREM-1 were 71.8 and 92.3%, and the sensitivity and specificity of sTREM-1 combined with PCT were 74.4 and 96.2%. Serum PCT combined with sTREM-1 accurately predicted the outcome of EOP patients, and dynamic monitoring of serum PCT and sTREM-1 levels is necessary.
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Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Calcitonina/sangre , Células Mieloides/metabolismo , Neumonía/complicaciones , Precursores de Proteínas/sangre , Receptores Inmunológicos/metabolismo , Accidente Cerebrovascular/complicaciones , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Péptido Relacionado con Gen de Calcitonina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía/sangre , Accidente Cerebrovascular/sangre , Tasa de Supervivencia , Adulto JovenRESUMEN
The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.
Asunto(s)
Animales , Ratas , Antiinflamatorios/uso terapéutico , Ácido Glutámico/toxicidad , Ácido Glicirrínico/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , /efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , /aislamiento & purificación , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromonas/farmacología , Citocromos c/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Morfolinas/farmacología , /clasificación , /citología , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , /aislamiento & purificación , /aislamiento & purificaciónRESUMEN
Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues that form the pancreas. To investigate whether the tribbles homolog 1 (Drosophila) gene (TRIB1) is associated with pancreatic cancer in the Chinese Han population, we conducted this case-control study and genotyped 3 single nucleotide polymorphisms (rs2980879, rs2980874, and rs2235108) of the TRIB1 gene in 182 patients and 359 normal controls of Chinese Han origin and analyzed their association. The results showed that the rs2980879 polymorphism was associated with pancreatic cancer [allele: P = 0.023434, genotype: P = 0.03005; odds ratio (OR) and 95% confidence interval (CI) = 0.727788 (0.552664-0.958404)], whereas the rs2980874 polymorphism had no association with pancreatic cancer [allele: P = 0.749885, genotype: P = 0.699533; OR and 95%CI = 1.041981 (0.809196-1.341734)], and the rs2235108 polymorphism was not associated with the disease [allele: P = 0.629475, genotype: P = 0.547534, OR and 95%CI = 1.128290 (0.690829-1.842770)]. Haplotype analyses and linkage disequilibrium tests were also conducted, and the results showed that these 3 loci are not in the same block. In conclusion, our study indicated that the TRIB1 gene is associated with pancreatic cancer. More studies with larger samples are needed in order to support this finding.
Asunto(s)
Estudios de Asociación Genética , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Pancreáticas/genética , Polimorfismo de Nucleótido Simple , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.
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Antiinflamatorios/uso terapéutico , Ácido Glutámico/toxicidad , Ácido Glicirrínico/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Células PC12/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/aislamiento & purificación , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromonas/farmacología , Citocromos c/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Morfolinas/farmacología , Células PC12/clasificación , Células PC12/citología , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/aislamiento & purificación , Ratas , Proteína X Asociada a bcl-2/aislamiento & purificaciónRESUMEN
This study investigated the induced immune tolerance of autoantigen dendritic cells (imDCs) in homogenic lupus mice to support the use of dendritic cell treatment against autoimmune diseases, such as systemic lupus erythematosus. A lupus mouse was used to model based on in vitro cell culture. An immunohistochemistry assay was used to assess CD8(+), CD4(+) cell ratio in mouse spleen cells. The ratio of CD4(+)CD25(+) cells in mouse spleen lymphocytes was detected by flow cytometry, whereas the kidney was directly measured by immunofluorescence. After the injection of mouse antigen loaded bone marrow-derived antigen imDCs with a homogenetic background, mouse nucleoprotein immune with a homogenetic background was carried out. The results were compared against the simple mouse nucleoprotein immune model with a homogenic background. The 24-h urine protein, serum antinuclear antibody and anti-ds-DNA antibodies of the simple mouse model were lower compared to group S1. The CD4(+)CD25(+) cell percentage of spleen was higher in the simple mouse model compared to group S1. In the spleen, the number of lymphocyte CD8(+) cells declined, whereas the number of CD4(+) cells increased. In conclusion, after autoantigen uptake, imDCs are able to induce immune tolerance to the antigen by reinfusion, which appears to prevent or mitigate systemic lupus erythematosus-like illness.
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Autoantígenos/inmunología , Células Dendríticas/trasplante , Lupus Eritematoso Sistémico/terapia , Bazo/inmunología , Animales , Recuento de Linfocito CD4 , Células Cultivadas , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/patología , Ratones , Ratones Endogámicos BALB C , Tolerancia al TrasplanteRESUMEN
We investigated the immune response effects of porcine circovirus type 2 (PCV2) on cells inoculated with pseudorabies attenuated vaccine (PRV). Real-time PCR was used to detect the mRNA expression levels of the regulatory cytokines IL-4, IL-10, IL-12p40, and IFN-γ in pig peripheral blood mononuclear cells, after in vitro single vaccination and co-inoculation with PCV2 and the PRV. We found that PRV causes upregulation of IL-4, IL-12p40, and IFN-γ mRNA expression, while PCV2 causes mRNA upregulation of IL-4, IL-10, and IL-12p40. Moreover, PCV2 inhibited PRV-induced upregulation of IL-4, IL-12p40, and IFN-γ mRNA expression; IFN-γ mRNA expression was significantly inhibited. We conclude that PCV2 can reduce the cellular immune response to PRV.
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Circovirus/genética , Citocinas/inmunología , ARN Mensajero/genética , Vacunas/inmunología , Animales , Circovirus/inmunología , Circovirus/patogenicidad , Citocinas/genética , Regulación de la Expresión Génica/inmunología , Humanos , Leucocitos Mononucleares , ARN Mensajero/inmunología , Porcinos/virología , Vacunas/genéticaRESUMEN
BACKGROUND: The nuclear protein Sam68 has been implicated in the oncogenesis and tumor growth. The aim of this study was to explore the clinical value of Sam68 in patients with non-small cell lung cancer (NSCLC). METHODS: We examined Sam68 expression in 50 NSCLC tissues and matched adjacent noncancerous tissues by quantitative RT-PCR (qRT-PCR) and Western blotting. Furthermore, the Sam68 protein expression was analyzed by immunohistochemistry in 208 NSCLC samples. Kaplan-Meier method and multivariate Cox regression model were used to evaluate the prognostic value of nuclear Sam68 expression in NSCLC for disease survival. RESULTS: The expression of Sam68 was significantly elevated in NSCLC tissues as compared with adjacent non-cancerous tissues (P < 0.01). The high expression of Sam68 in NSCLC was significantly correlated with lymph node metastasis and tumor TNM stage. Kaplan-Meier survival analysis revealed that high expression of Sam68 correlated with poor prognosis of NSCLC patients (P < 0.01). Multivariate analysis showed that Sam68 expression was an independent prognostic marker for overall survival of NSCLC patients (HR 2.73, 95 % CI 1.549-4.315, P = 0.002). CONCLUSION: Our results suggest that high Sam68 expression predicts poor prognosis of NSCLC patients, and Sam68 may be potentially a prognostic biomarker for NSCLC.
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Proteínas Adaptadoras Transductoras de Señales/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas de Unión al ADN/genética , Neoplasias Pulmonares/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores de Tumor/metabolismo , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Estudios de Cohortes , Proteínas de Unión al ADN/metabolismo , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas de Unión al ARN/metabolismo , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
PURPOSE: CKLF-like MARVEL transmembrane domain containing member 3 (CMTM3) is silenced in many kinds of cancers and inhibits tumor cells growth. We investigated the expression and role of CMTM3 in clear cell renal cell carcinoma (ccRCC). METHODS: The expression of CMTM3 was detected in ccRCC tissue microarray, specimens, and cell lines by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. After transfected with CMTM3 plasmid or vector, the proliferation and migration of ccRCC 786-0 cells were determined by MTT assay and transwell assay, respectively. Furthermore, the anchorage-independent growth of transfected cells was assessed using soft agar colony formation assay. RESULTS: CMTM3 was down-regulated in 84 % (63/75) of ccRCC tissues and its expression had no correlation with the gender, age, clinical staging and histologic grade. CMTM3 protein was undetectable by western blot in most detected ccRCC specimens and two RCC cell lines (786-0 and ACHN). qRT-PCR analysis showed that CMTM3 mRNA was dramatically down-regulated in 40 ccRCC cancer tissues as compared with the paired adjacent normal ones. Restoration of CMTM3 significantly suppressed the anchorage-independent growth, proliferation and migration of 786-0 cells. CONCLUSION: These results indicate that CMTM3 is significantly down-regulated in ccRCC and exerts remarkable tumor-suppressive functions in 786-0 cells. Reduction of CMTM3 expression may contribute to the pathogenesis of ccRCC and CMTM3 may be a potentially target for therapeutic strategy.