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Astragaloside IV, the active component of Astragalus membranaceus, exhibits diverse biological roles including the anti-tumor activity. In this study, we evaluated the chemosensitive role of astragaloside IV in non-small cell lung cancer cells. Cell Counting Kit-8 analysis was performed to determine cell viability. Real-time polymerase chain reaction and western blot were used to measure the messenger RNA and protein expression. Results showed that astragaloside IV treatment could suppress the proliferation of non-small cell lung cancer cells. In addition, combined treatment with astragaloside IV remarkably enhanced the chemosensitivity to gefitinib in three non-small cell lung cancer cell lines including NCI-H1299, HCC827, and A549. Furthermore, compared with gefitinib-treated cells, the messenger RNA expression of SIRT6 was obviously increased in non-small cell lung cancer cells treated with gefitinib combined with astragaloside IV. In addition, downregulation of SIRT6 was accomplished using small interference RNA technology. As a result, SIRT6 inhibition abolished the sensitization role of astragaloside IV in non-small cell lung cancer cells. Taken together, these data demonstrated that astragaloside IV sensitized tumor cells to gefitinib via regulation of SIRT6, suggesting that astragaloside IV may serve as potential therapeutic approach for lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quinazolinas/administración & dosificación , Saponinas/administración & dosificación , Sirtuinas/biosíntesis , Triterpenos/administración & dosificación , Células A549 , Apoptosis/efectos de los fármacos , Astragalus propinquus/química , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Gefitinib , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Sirtuinas/genéticaRESUMEN
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide and is proved to be the number three cause of death in globally. The objective of this study was to explore the molecular mechanism of the progression of COPD. METHODS: Using the GSE1650 affymetrix microarray data accessible from Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) between 18 COPD samples and 12 normal samples, followed by the GO / KEGG pathway analysis and gene interaction networks analysis of the DEGs. Our study identified 134 DEGs which involved in regulation of immune response, vesicle transport system, growth regulator and extracellular matrix (ECM)-related pathways. RESULTS: Gene interaction networks analysis showed that the sub-network involved by activating transcription factor-3 (ATF3) was the most significant sub-network in gene interaction networks. Furthermore, the investigation of extracellular matrix-related genes showed that genes like collagen and insulin-like growth factor binding protein could clearly distinguish the COPD and normal control. CONCLUSIONS: The genes regulated by ATF3 transcriptional activator as well as ECM-related genes may play an important role in the process of COPD. Our study provides a comprehensive bioinformatics analysis of genes and pathways which may be involved in the progression of COPD.
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Factor de Transcripción Activador 3/genética , Matriz Extracelular/genética , Regulación de la Expresión Génica , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Valores de Referencia , Medición de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Repeated intratracheal injection of Pseudomonas aeruginosa (PA) in male Wistar rats was used to investigate the role of chronic infection in the development of chronic obstructive pulmonary disease (COPD) and the possible involvement of connective tissue growth factor (CTGF) and bone morphogenetic protein-7 (BMP-7) in this process. Injections of PA or normal saline solution were given for 8 weeks and the rats observed for a further 8 weeks. In addition to arterial blood gas, lung function and lung pathology measurement during this time period, protein and mRNA expression of CTGF and BMP-7 were measured, and the correlation of expression of CTGF and BMP-7 with pathological changes in the lung was evaluated. Repeated intratracheal PA infection in rats caused reduction in body weight, hypoxia, carbon dioxide retention, compromised lung function, chronic inflammation, thickening of the tracheal and arterial walls, and emphysema, changes consistent with those of COPD. Rats with PA infection also had increased CTGF and decreased BMP-7 expression, suggesting that both CTGF and BMP-7 are involved in the occurrence and development of airway remodeling. Our findings suggest that repeated airway infection is not only a factor resulting in deterioration of COPD, but is also a risk factor for its development, and that CTGF and BMP-7 are involved in the pathogenesis of this condition.
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Proteína Morfogenética Ósea 7/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Infecciones por Pseudomonas/complicaciones , Pseudomonas aeruginosa , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Animales , Proteína Morfogenética Ósea 7/genética , Factor de Crecimiento del Tejido Conjuntivo/genética , Modelos Animales de Enfermedad , Masculino , Infecciones por Pseudomonas/metabolismo , Infecciones por Pseudomonas/patología , Enfermedad Pulmonar Obstructiva Crónica/patología , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVE: To explore whether injury and repair occur in the trachea and the lung after intra-tracheal administration of different drugs. METHODS: Wistar rats were randomly divided into 5 groups, a normal group, a blank control (BC) group, a normal saline (NS) group, a lidocaine (LD) group and an amikacin (AK) group. For the latter 3 groups, normal saline, lidocaine and amikacin were injected into trachea by needle puncture. Scanning electron microscope was used to observe the ultra-structural changes of the epithelium, and the percentage of the area of damage (PAD) in tracheal mucosa was calculated. Moreover, pathological changes of the mucous membrane of bronchioles and alveolar epithelial cells were also examined, and the degree of lung pathology was semi-quantified. RESULTS: Two hours after the injection of the 3 drugs, derangement and edema of the cilia were evident by scanning electron microscopy. The PAD of the NS group, the LD group and the AK group were (94.2 ± 3.2)%, (93.1 ± 3.0)% and (95.5 ± 1.8)%, respectively; all being significantly higher than that of the BC group (1.3 ± 0.3)%. For the NS group and the LD group, the PAD decreased significantly after 24 h, which were (73.7 ± 7.8)% and (81.0 ± 4.6)% respectively, and returned to normal at 48 h and 96 h. While for the AK group, the damage began to improve at 72 h [PAD (62.1 ± 5.2)%], and recovered at 96 h. Airway epithelial derangement and cell edema in the alveoli and the bronchioles also occurred 2 h after drug injection, and inflammatory cell infiltration became evident at 24 h. At this time, the score of pathology was 1.80 ± 0.84, 2.60 ± 0.55 and 2.80 ± 0.45 for the NS group, the LD group and the AK group, respectively; all being higher than that of the BC group (0). These pathological changes recovered totally after 72 h for the NS and the LD groups, and 96 h for the AK group. CONCLUSIONS: Intra-tracheal administration of normal saline, lidocaine and amikacin in rats led to reversible airway mucosal and lung tissue damages.
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Inyecciones/efectos adversos , Tráquea/lesiones , Animales , Lesión Pulmonar/etiología , Masculino , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To investigate the clinical features, radiology, diagnosis and treatment of pulmonary cryptococcosis. METHODS: A total of 38 cases of pulmonary cryptococcosis, confirmed by pathological examinations at Fuzhou General Clinical Medical College, Fujian Medical University from March 2003 to February 2010, were retrospectively studied. RESULTS: All of the cases were community-acquired. The patients consisted of 29 males and 9 females, aged from 21 to 70 years. There were no underlying diseases in 29 cases. The CD(4) cell numbers were normal in 20 patients. Radiological study showed that the majority of the lesions (35 cases) were close to the pleura. Lower lungs were often involved (left 21 and right 23). Pulmonary nodules, either solitary nodules (11 cases) or multiple nodules (16 cases), were the most common CT finding. The lesions had a higher standardized uptake value (SUV) in 4 patients with a PET-CT scan. The lung specimens of 33 cases were obtained by CT guided transthoracic needle aspiration biopsy. The disease was cured in 34 cases, and improved in 3 cases, but 1 died. CONCLUSIONS: Pulmonary cryptococcosis must be considered in the differential diagnosis of lesions of the lungs. The disease has some characteristics on radiology, such as multiple lesions, always close to the pleura and occurs frequently in the lower lungs. CT guided percutaneous biopsy is a safe and effective method for diagnosis.
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Criptococosis/diagnóstico , Enfermedades Pulmonares Fúngicas/diagnóstico , Adulto , Anciano , Criptococosis/patología , Cryptococcus , Femenino , Humanos , Pulmón/patología , Enfermedades Pulmonares Fúngicas/microbiología , Enfermedades Pulmonares Fúngicas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
The capability of detecting biomarkers, such as amino acids, in chemically complex field samples is essential to establishing the knowledge required to search for chemical signatures of life in future planetary explorations. However, due to the complexities of in situ investigations, it is important to establish a new analytical scheme that utilizes a minimal amount of sample preparation. This paper reports the feasibility of a novel and sensitive technique, which has been established to quantitate amino acids in terrestrial crust samples directly without derivatization using volatile ion-pairing liquid chromatography and tandem mass spectrometry equipped with an electrospray ionization source. Adequate separation of 20 underivatized amino acids was achieved on a C(18) capillary column within 26 min with nonafluoropentanoic acid (NFPA) as ion-pairing reagent. Each amino acid was identified from its retention time as well as from its characteristic parent-to-daughter ion transition. Using tandem mass spectrometry as a detection technique allows co-elution of some amino acids, as it is more specific than traditional spectrophotometric methods. In the present study, terrestrial samples collected from 3 different locations were analyzed for their water-extractable free amino acid contents, following the removal of metal and organic interferences via ion exchange procedures. This is the first time that amino acids in geological samples were directly determined quantitatively without complicated derivatization steps. Depending on the amino acid, the detection limits varied from 0.02 to 5.7 pmol with the use of a 1 microl sample injection loop.
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Aminoácidos/análisis , Cromatografía Liquida/métodos , Geología , Espectrometría de Masa por Ionización de Electrospray/métodos , Aminoácidos/química , Técnicas de Laboratorio Clínico , Estudios de Factibilidad , Fenómenos Geológicos , Sensibilidad y EspecificidadRESUMEN
The safety of vegetable production is a key link in reducing cadmium consumption through the food chains. Field experiments were conducted to investigate the effects of composite materials (calcium silicate-biological humus fertilizer) on the growth of shallots and the uptake of Cd by shallots from contaminated agricultural soil. Four treatments (T1: 0.5% calcium silicate+0.5% biological humus fertilizer; T2: 0.5% calcium silicate+1.0% biological humus fertilizer; T3: 1.0% calcium silicate+0.5% biological humus fertilizer; and T4: 1.0% calcium silicate+1.0% biological humus fertilizer) and a control group (CK) were adopted. The changes in soil pH, DTPA-extractable Cd, biomass of shallots, and cadmium concentrations in shallots over time under different treatments were analyzed. The results show that the application of composite amendments decreased the concentrations of DTPA-extractable Cd in the soil. In particular, after T3 treatment, the concentrations of soil DTPA-extractable Cd decreased by 60.71%, 49.54%, 44.63%, and 58.94% after 14, 28, 42, and 56 d, respectively. The biomass of the shallots aboveground increased significantly by 107.99% and 107.19% after T3 and T4 treatment, respectively. The composite amendments exhibited different effects on the uptake of Cd by the shallots from the soil, and the T4 treatment was the most effective in immobilizing Cd and inhibiting translocation of Cd into the shallots. The cadmium concentration in the shallots decreased by 43.80% after 56 d with the T4 treatment. In conclusion, T4 is the optimum treatment for soil cadmium immobilization.
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Cadmio/metabolismo , Compuestos de Calcio/química , Fertilizantes , Chalotes/metabolismo , Silicatos/química , Contaminantes del Suelo/metabolismo , Suelo/química , Chalotes/efectos de los fármacosRESUMEN
The massive release of soil arsenic and its enrichment in rice are significantly associated with the flooded and anaerobic management in paddy soil. Soil redox potential (Eh), pH and iron oxides exert remarkable impacts on arsenic release, which remain to be explored. In this study, long-term aerobic and anaerobic as well as intermittent aerobic incubation treatments were applied to investigate the influences of Eh, pH and iron content on arsenic release. It was found that anaerobic and flooded treatment contributed to the highest arsenic release. With decreasing Eh, significant enhancement in As(â ¢) and As(â ¤) contents in soil solution was observed. Particularly, As(â ¢) and As(â ¤) contents during the second phase increased by 1.37 and 0.99 µg·L-1compared with those in the first phase. Conversely, significant reduction in soil arsenic release (P<0.05) occurred when intermittent aerobic treatment was adopted, and the lowest level of arsenic release was observed along with the longest treatment time (6 d). The exponent relationships between arsenic and soil Eh, pH and Fe2+ content were also established, which indicated that arsenic release could be accelerated by lower pH and elevated Eh. In addition, a significant positive correlation was also found between iron(â ¡) content and arsenic content in soil solution. Since low Eh and elevated pH served as critical factors driving arsenic release, intermittent and aerobic water management was proved to be an effective method for the inhibition of arsenic release and uptake and accumulation of arsenic by rice.
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Arsénico/química , Hierro/química , Oryza , Contaminantes del Suelo/química , Oxidación-Reducción , SueloRESUMEN
MicroRNAs (miRNAs) are a class of small non-coding RNAs that play key roles in cancer development and progression. Therefore, the discovery of miRNAs may provide a new and powerful tool for understanding the mechanism of carcinogenesis. In the present study, we aimed to investigate the functional significance of miR-630 and to identify its possible target genes in human non-small cell lung cancer (NSCLC). Our results showed that miR-630 was significantly down-regulated in NSCLC tissues and cell lines. The enforced expression of miR-630 was able to inhibit cell proliferation, migration, and invasion of NSCLC cells. Moreover, our results further revealed that LMO3, a nuclear LIM-only proteins, was identified as a target of miR-630. Restoration of LMO3 remarkably reversed the tumor-suppressive effects of miR-630 on cell proliferation, migration, and invasion in NSCLC cells. Therefore, we demonstrated that miR-630 suppressed the proliferation, migration, and invasion of NSCLC cells by down-regulating LMO3 expression, suggesting miR-630 as a potential therapeutic target for the treatment of human NSCLC in the future.
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OBJECTIVE: To evaluate the inhibitory effect of recombinant human endostatin on tumor growth and metastasis of adenocarcinoma LA795 in mice. METHODS: Recombinant human endostatin was purified rom endostadin-expressing pCX clones. LA795 cells were inoculated subcutaneously on the back of T739 mice, which were randomized into 2 groups. From the tenth day on, treatment group was given 20 mg/kg recombinant human endostatin subcutaneously daily for 14 consecutive days, and the control group received PBS in the same manner. The sizes of the subcutaneous tumors, lung weights, the number of metastases over the lung surface and the survival time of the mice were observed. RESULTS: The tumor sizes of the treatment group in creased slowly from (650+/-201) mm3 to (1 642+/-21) mm3 when compared with those of the control group which showed and increase from (623+/-248) mm3 to (9 194+/-952) mm3. The lung weight of the 2 groups was (190+/-25) mg and (324+/-43) mg respectively, and the number of lung sung surface metastases was 8+/-2 and 22+/-8 for each. The average survival time of the rats in the 2 groups was 48 d and 27 d, respectively. All parameters measured between the 2 groups showed significant differences (P<0.01). CONCLUSION: Recom binent human endostatin has strong inhibitory effect on both the growth of primary tumor and metastasis of lung adenocarcinoma LA795 cells, and prolongs the survival time of the tumor-bearing mice.
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Adenocarcinoma del Pulmón/diagnóstico , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios RetrospectivosRESUMEN
Photolysis of heptanal is investigated from an experimental and theoretical point of view. Photoexcited heptanal is believed to undergo rapid intersystem crossing to the triplet manifold and from there undergoes internal H-abstraction to form biradical intermediates. The favored gamma-H abstraction pathway can cyclize or cleave to 1-pentene and hydroxyethene, which tautomerizes to acetaldehyde. Yields of 1-pentene and acetaldehyde were measured at 62 +/- 7% and 63 +/- 7%, respectively, relative to photolyzed heptanal. Additionally, small quantities of hexanal and hexanol were observed. On the basis of combined experimental and theoretical evidence, the remaining heptanal photolysis proceeds to form an estimated 10% HCO + hexyl radical and 30% cyclic alcohols, particularly 2-propyl cyclobutanol and 2-ethyl cyclopentanol.