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Gefitinib is the first-generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolised by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were administered a single dose of gefitinib and the blood samples were used for quantifying the concentration of gefitinib and genotyping fifteen single-nucleotide polymorphisms of cytochrome P450 enzymes (CYP3A4, CYP3A5, CYP2D6, CYP2C9 and CYP2C19) and drug transporters (ABCB1 and ABCG2).CYP3A5*3 (rs776746) polymorphism showed a significant influence, with higher gefitinib AUC0-t in carrier of CC genotype than in CT/TT genotype (BH-adjusted p value <0.05). For CYP2C9*3 (rs1057910), significant differences in pharmacokinetics of gefitinib were detected between carriers of AA and AC genotypes, with higher AUC0-t, AUC0-∞ and Cmax in carrier of AC genotype than in AA gen-otype (BH-adjusted p value <0.05). No associations were found between SNPs in CYP3A4, CYP2D6, CYP2C19, ABCB1, ABCG2 and the pharmacokinetics of gefitinib.The SNPs in CYP3A5*3 (rs776746) and CYP2C9*3 (rs1057910) were found to be associated with altered gefitinib pharmacokinetics in healthy Chinese volunteers.
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Citocromo P-450 CYP2D6 , Citocromo P-450 CYP3A , Humanos , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Gefitinib , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Voluntarios Sanos , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2C9/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Polimorfismo de Nucleótido Simple , Genotipo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , ChinaRESUMEN
OBJECTIVE: To investigate the effect of acrolein on the proliferation of pulmonary epithelial cells and its possible mechanism. METHODS: Two strains of pulmonary epithelial cells, A549 cells and MLE15 cells, were used as in vitro models of pulmonary epithelial cell, and were treated with 80 µmol/L acrolein or phosphate buffer saline (PBS) as the control. The proliferation of pulmonary epithelial cells were determined with CCK-8 kit after cell culturing resumed for 12 h, 24 h, 36 h and 48 h post acrolein treatment, and the expression of period circadian regulator gene 1 ( Per1) was examined using Western blot test 24 h after acrolein treatment. In addition, after acrolein treatment, the cells were restored with transforming growth factor-ß (TGF-ß) added in the medium, and the cell proliferation and the expression of Per1 protein were also examined. RESULTS: The proliferation of A549 cells and MLE15 cells decreased significantly after being treated with 80 µmol/L acrolein for 30 min, and the expression of Per1 protein was also downregulated significantly ( P<0.05). The addition of TGF-ß after acrolein treatment did not significantly change the reduction in cell proliferation caused by acrolein, but the expression of Per1 protein in pulmonary epithelial cells was significantly higher than that in cells restored without TGF-ß ( P<0.05). CONCLUSION: Acrolein treatment resulted in the decreased proliferation of pulmonary epithelial cells and the Per1 expression in pulmonary epithelial cells. Although TGF-ß addition did not reverse the reduction of cell proliferation after acrolein treatment, the Per1 expression levels were recovered to a certain extent compared to that in cells restored in medium without TGF-ß after acrolein treatment.
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Acroleína , Células Epiteliales , Acroleína/farmacología , Proliferación Celular , Expresión Génica , PulmónRESUMEN
Based on the software of traditional Chinese medicine inheritance support system (TCMISS), this article aims to analyze the experience and composition rules for cough from the descendant of Meng He Medical School, Xu Di-hua. The cough cases treated by Xu Di-hua were collected, and recorded into TCMISS (V2.0). Data mining methods such as Apriori algorithm and complex system entropy cluster were used to analyze the medication principles of Xu Di-hua for cough from pathogenesis and therapeutie aspects, and dig out the frequency of the herbs in prescription, core medicine and new combinations. The experience of curing cough from Professor Xu Di-hua were well found in the research. He is good at choosing prescriptions accurately, and pays attention to simultaneous use of cold and moisture drugs with combination of tonification and purgation. He is skilled in adding or reducing materia medica flexibly, as well as regulating lung to relieve cough and eliminating phlegm by clearing heat.
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Tos/tratamiento farmacológico , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Algoritmos , Minería de Datos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Materia Medica , Medicina Tradicional ChinaRESUMEN
Flow cytometry, in conjunction with immunoprecipitation (IP-FCM), is suggested to have some advantages to conventional IP-western blot technology in analyzing protein complexes. In this paper, to further examine its practicability, we test the use of IP-FCM in detecting the HSP90 complex, which has gained importance in drug research and development and involves more than a dozen components. We found that IP-FCM could effectively detect HSP70, p23, Cdc37, and Cdk6 components in the HSP90 complex naturally formed in U937 cells when this complex was captured by anti-HSP90 antibody-coated polystyrene microspheres. IP-FCM could also detect alteration in components caused by treating cells with HSP90 inhibitors. In a cell-free environment, IP-FCM could detect the direct effects of ATP and/or HSP90 inhibitors (17-N-allylamino-17-demethoxygeldanamycin or celastrol) in causing component dissociation and the time- and dose-effects of inhibitor-caused dissociation. IP-FCM is a practical and powerful platform for analyzing HSP90 complex components, and is thus a useful tool in studying HSP90 complex function and screening inhibitors.
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Citometría de Flujo/métodos , Proteínas HSP90 de Choque Térmico/análisis , Inmunoprecipitación/métodos , Western Blotting , Línea Celular Tumoral , Humanos , MicroesferasRESUMEN
We present a high-resolution (HR) reconstruction model and algorithms for terahertz imaging, taking advantage of super-resolution methodology and algorithms. The algorithms used include projection onto a convex sets approach, iterative backprojection approach, Lucy-Richardson iteration, and 2D wavelet decomposition reconstruction. Using the first two HR reconstruction methods, we successfully obtain HR terahertz images with improved definition and lower noise from four low-resolution (LR) 22×24 terahertz images taken from our homemade THz-TDS system at the same experimental conditions with 1.0 mm pixel. Using the last two HR reconstruction methods, we transform one relatively LR terahertz image to a HR terahertz image with decreased noise. This indicates potential application of HR reconstruction methods in terahertz imaging with pulsed and continuous wave terahertz sources.
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Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson's disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+), respectively. Ferroptosis was identified by assessing the levels of Fe2+, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe2+, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP+-induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP+-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.
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Modelos Animales de Enfermedad , Neuronas Dopaminérgicas , Ferroptosis , Flavonoides , Especies Reactivas de Oxígeno , Ferroptosis/efectos de los fármacos , Animales , Flavonoides/farmacología , Ratas , Masculino , Especies Reactivas de Oxígeno/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Humanos , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Línea Celular Tumoral , Hierro/metabolismo , alfa-Sinucleína/metabolismo , Ratas Sprague-Dawley , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/efectos adversos , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
Background: The association between body mass index (BMI) and rapid eye-movement (REM) sleep-related behavioral disorder (RBD) in Parkinson's disease (PD) remains unknown. Our study was to investigate the association of BMI with RBD in PD patients. Methods: In this cross-sectional study, a total of 1,115 PD participants were enrolled from Parkinson's Progression Markers Initiative (PPMI) database. BMI was calculated as weight divided by height squared. RBD was defined as the RBD questionnaire (RBDSQ) score with the cutoff of 5 or more assessed. Univariable and multivariable logistic regression models were performed to examine the associations between BMI and the prevalence of RBD. Non-linear correlations were explored with use of restricted cubic spline (RCS) analysis. And the inflection point was determined by the two-line piecewise linear models. Results: We identified 426 (38.2%) RBD. The proportion of underweight, normal, overweight and obese was 2.61, 36.59, 40.36, and 20.44%, respectively. In the multivariate logistic regression model with full adjustment for confounding variables, obese individuals had an odds ratio of 1.77 (95% confidence interval: 1.21 to 2.59) with RBD compared with those of normal weight. In the RCS models with three knots, BMI showed a non-linear association with RBD. The turning points of BMI estimated from piecewise linear models were of 28.16 kg/m2, 28.10 kg/m2, and 28.23 kg/m2 derived from univariable and multivariable adjusted logistic regression models. The effect modification by depression on the association between BMI and RBD in PD was also found in this study. Furthermore, the sensitivity analyses linked with cognition, education, and ethnic groups indicated the robustness of our results. Conclusion: The current study found a significant dose-response association between BMI and RBD with a depression-based difference in the impact of BMI on RBD in PD patients.
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Terahertz time-domain spectroscopy was employed to measure the terahertz absorption spectra of benzoic acid and sodium benzoate at room temperature. The origins of the measured features of benzoic acid were summarized based on previous study. Density functional theory was used to compute and analyze the molecular structure and vibrational modes of sodium benzoate in monomer. Based on the obtained results, the authors found that the THz spectral features can be used to distinguish benzoic acid and sodium benzoate totally; the essential reason for the THz spectral difference between benzoic acid and sodium benzoate is that the electrovalent bond of sodium benzoate affects the values of covalent bond lengths and bond angles, as well as the molecular interactions and arrangement in unit cell; the measured features of benzoic acid and sodium benzoate come from the collective vibrations except the peaks located at 107 cm-1 of benzoic acid and 54 cm-1 of sodium benzoate.
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This study aimed to identify the potential circular RNAs (circRNAs) in exosomes isolated from serum as biomarkers of lower limb vascular disease (LLVD) in patients with type 2 diabetes mellitus (T2DM). This research collected circRNAs from exosomes isolated from three T2DM patients and three T2DM patients with LLVD for microarray analysis. Five candidate biomarkers derived from differentially expressed circRNAs were then validated by quantitative real-time polymerase chain reaction in 20 T2DM patients and 20 T2DM patients with LLVD. Finally, expression levels of circRNAs were validated in 160 samples. Significant differences in the expression of 295 circRNAs were found between T2DM controls and T2DM patients with LLVD. Among them, 191 differentially expressed circRNAs were upregulated, and 104 were downregulated in T2DM patients with LLVD. Three upregulated and two downregulated circRNAs were further confirmed in 40 samples. According to the testing of 160 samples, hsa_circ_0001842 showed a noticeable specificity in the T2DM patients with LLVD group (n = 80), with an area under the curve (AUC) of 0.79, a sensitivity of 88.75%, and a specificity of 68.75%. In conclusion, hsa_circ_0001842 was found as a potential diagnostic biomarker for T2DM with LLVD.
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Diabetes Mellitus Tipo 2 , ARN Circular , Humanos , ARN Circular/genética , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Biomarcadores/metabolismo , Análisis por Micromatrices , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Introduction: Cognitive impairment includes the abnormality of learning, memory and judgment, resulting in severe learning and memory impairment and social activity impairment, which greatly affects the life quality of individuals. However, the specific mechanisms underlying cognitive impairment in different behavioral paradigms remain to be elucidated. Methods: The study utilized two behavioral paradigms, novel location recognition (NLR) and novel object recognition (NOR), to investigate the brain regions involved in cognitive function. These tests comprised two phases: mice were presented with two identical objects for familiarization during the training phase, and a novel (experiment) or familiar (control) object/location was presented during testing. Immunostaining quantification of c-Fos, an immediate early gene used as a neuronal activity marker, was performed in eight different brain regions after the NLR or NOR test. Results: The number of c-Fos-positive cells was significantly higher in the dorsal part of the lateral septal nucleus (LSD) in the NLR and dentate gyrus (DG) in the NOR experiment group than in the control group. We further bilaterally lesioned these regions using excitotoxic ibotenic acid and replenished the damaged areas using an antisense oligonucleotide (ASO) strategy. Discussion: These data reinforced the importance of LSD and DG in regulating spatial and object recognition memory, respectively. Thus, the study provides insight into the roles of these brain regions and suggests potential intervention targets for impaired spatial and object recognition memory.
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Risk avoidance behaviors are essential for survival. "Uncontrollable" risk-taking behaviors in animals or humans may have severe adverse consequences. In humans, a large proportion of psychiatric disorders are accompanied by impairments in risk avoidance. Obesity is associated with psychiatric disorders. Peroxisome proliferator-activated receptor α (PPARα) takes part in regulating lipid metabolism and neuronal function. Here, we investigated the effect of high-fat diet (HFD)-induced obesity on risk avoidance and the role of PPARα in this behavior. Male PPARα-null (KO) mice and wild-type (WT) mice were assigned to four different groups: WT-CON and KO-CON (normal diet); WT-HFD and KO-HFD (high fat diet). The HFD began at week 6 and was continued until sampling. A series of behavioral tests were performed at week 11. We found that WT but not KO mice fed with a HFD exhibited weight gain and risk avoidance impairment, compared with the mice fed with a normal diet. The staining of c-Fos revealed that the hippocampus was the main brain region involved in risk avoidance behavior. Moreover, biochemical analysis suggested that the decreased levels of the brain-derived neurotrophic factor (BDNF) in the hippocampus might contribute to risk avoidance impairment induced by a HFD. These results indicated that PPARα is involved in HFD-induced risk avoidance impairment via the regulation of hippocampal BDNF.
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Dieta Alta en Grasa , PPAR alfa , Humanos , Ratones , Masculino , Animales , Dieta Alta en Grasa/efectos adversos , PPAR alfa/genética , PPAR alfa/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Obesidad/metabolismo , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
OBJECTIVE: To quantitatively investigate the characteristics of the microsaccadic eye-movements in anisometropic amblyopia and to evaluate the using value of high-speed eye-movement recording in objective and quantitative evaluation and diagnosis of amblyopia. METHODS: From September in 2010 to March in 2011, 19 cases of anisometropic amblyopic patients (19 amblyopic eyes as group AM and 19 their sound eyes as group AS) and 19 cases of subjects with normal corrected visual acuities (19 dominant eyes as group ND and 19 non-dominant eyes as group NN) were recruited from the outpatient clinic at Tianjin Eye Hospital. A high-speed eye-movement recording system was used to monocularly record the fixational eye-movements of subjects' both eyes. A Matlab routine was used to detect and analyze the microsaccadic components of eye-movement waveforms. The microsaccadic amplitudes, peak velocities, occurrence rates, inter-microsaccadic intervals, cumulative probabilities of all groups were analyzed and compared using Origin8.0 and Matlab2008 statistics toolbox. RESULTS: The mean microsaccadic amplitude of group AM (0.76 ± 0.07)° was larger than groups AS, ND and NN (F = 49.95, P = 0.000). The mean peak velocity of group AM (79.72 ± 5.64)°/s was faster than groups AS, ND and NN (F = 4.93, P = 0.004). The mean occurrence rate of group AM (1.52 ± 0.08) Hz was less than groups AS, ND and NN (F = 120.39, P = 0.000). The mean inter-microsaccadic interval of group AM (537.40 ± 65.47) ms was longer than groups AS, ND and NN (F = 4.41, P = 0.007). The amplitude dependent cumulative probability curve of group AM shifted to right compared with other groups and its amplitude 0.67° ± 0.06° at half cumulative probability was obviously increased compared with other groups (F = 203.05, P = 0.000). CONCLUSION: Microsaccadic amplitude, peak velocity, occurrence rate, inter-microsaccadic interval and cumulative probability could be used as the parameters for objective and quantitative evaluation of eye-movement function in amblyopia. High-speed eye-movement recording could provide useful assistance in evaluation of eye-movements in amblyopic patients.
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Ambliopía/fisiopatología , Anisometropía/fisiopatología , Movimientos Sacádicos , Adolescente , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Proyectos PilotoRESUMEN
We compared the therapeutic effects between botulinum toxin and surgery for acute acquired comitant esotropia (AACE) and analyze its clinical characteristics. The data of the 29 cases, who received treatment for AACE in the Ophthalmic Center of the First Affiliated Hospital of Zhengzhou University and Henan Provincial Ophthalmology Hospital between January 2016 and January 2017, were collected. The 29 cases with AACE were followed for 6 months or more, and received either botulinum toxin injection (group A with 13 cases) or squint correction (group B with 16 cases). The distant and near deviation angles were compared between the two groups before and after treatment. The success rate (total horizontal deviation of 10 prism diopters or less) and stereopsis were compared between the two groups at post-treatment 6 months. At the same time, the relations between distant and near deviation angles were analyzed among different myopia levels and different AACE types. Results indicated that he success rate was not significantly different at post-treatment 6 months (84.6% vs 81.3%, P = 1.00). The distant and near deviation angles were all significantly different one day and one month after treatment (all P < 0.05); but at post-treatment 6 months, they were not significantly different (all P > 0.05) between the two groups. There were no significant differences in the distant and near stereoacuity between the two groups at post-treatment 6 months (all P > 0.05). Among the 25 cases with myopia, the pre-treatment distant deviation angle was significantly higher than pre-treatment near deviation angle in the cases with myopia level >-2.5 D (P < 0.05), and the pre-treatment distant and near deviation angles were all significantly higher in the cases with type-IIAACE than in the cases with type-IIIAACE (all P < 0.05). This study suggests that Botulinum toxin is as effective as surgery in the treatment of AACE at post-treatment 6 months. For the cases with myopia level >-2.5 D, the pre-treatment distant deviation angle is significantly higher than pre-treatment near deviation angle; and both pre-treatment distant and near deviation angles are greater in the cases with type-IIAACE than in the cases with type-IIIAACE.
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Toxinas Botulínicas Tipo A/uso terapéutico , Esotropía/tratamiento farmacológico , Esotropía/cirugía , Adolescente , Adulto , Toxinas Botulínicas Tipo A/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
Cell adhesion molecules (CAM) expressed by vascular endothelium in response to cytokine stimulation play a key role in leukocyte adhesion to endothelium during the inflammatory response. Tripterine, a chemical compound of the Chinese plant Tripterygium wilfordii Hook f, displays anti-inflammatory properties in several animal models. However, mechanisms of its action are poorly understood. In the present study, we show that in inflammatory conditions, mimicked by tumor necrosis factor alpha (TNF-alpha) stimulation, pretreatment for 6 h with tripterine at nontoxic concentrations of 20-200 nM inhibits the expression of E-selectin, vascular cell adhesion molecule (CAM)-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner. Tripterine (200 nM) almost completely inhibits expression of VCAM-1 [50% inhibitory concentration (IC50) = 52 nM] and ICAM-1 (IC50 = 51 nM) and 73% of E-selectin (IC50 = 94 nM). This inhibition effect is prominent, compared with that of dexamethasone, ibuprofen, methotrexate, or probucol, which revealed a much weaker inhibition at doses as high as 1 mM. Effects on endothelial CAM of other proinflammatory cytokines, such as interleukin-1beta and interferon-gamma, were also inhibited significantly by tripterine. Moreover, significant inhibition was equally observable in postincubation experiments. In addition, tripterine inhibited adhesion of human monocytes and T lymphocytes to TNF-alpha-stimulated HUVEC. Finally, tripterine inhibited TNF-alpha-driven CAM mRNA transcription and nuclear factor-kappaB nuclear (NF-kappaB) translocation. Hence, we describe a new mechanism of tripterine's anti-inflammatory action obtained at nanomolar concentrations, owing to the negative regulation of cytokine-induced adhesion molecule expression and adhesiveness in human endothelium.
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Antiinflamatorios/farmacología , Moléculas de Adhesión Celular/metabolismo , Células Endoteliales/fisiología , Molécula 1 de Adhesión Intercelular/metabolismo , Triterpenos/farmacología , Molécula 1 de Adhesión Celular Vascular/metabolismo , Línea Celular , Proliferación Celular , Supervivencia Celular , Relación Dosis-Respuesta a Droga , Humanos , Interferón gamma/farmacología , Interleucina-1/farmacología , Modelos Moleculares , FN-kappa B/metabolismo , Triterpenos Pentacíclicos , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
OBJECTIVE: Increasing of adhesion between leukemia cells and endothelial cells during all-trans retinoic acid (ATRA) treatment plays an important role in retinoic acid syndrome. This work observed the effects of tripterine on this ATRA-caused increasing in adhesion. METHODS: The effects of tripterine on ATRA-induced expressions of adhesive molecules in acute promyelocytic leukemia cell line NB4 and human umbilical vascular endothelial cells (HUVEC) were detected by flow cytometry. The effects of tripterine on adhesion between ATRA-treated NB4 and HUVEC were determined by adhesive assays. RESULTS: ATRA caused remarkable elevation of intercellular adhesion molecule-1 (ICAM-1) in NB4 cells, which could be significantly reduced by tripterine (P<0.01). The expressions of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and ICAM-1 in HUVEC were elevated by conditioned medium from ATRA-induced NB4 (ATRA-NB4-CM) (P<0.01), and inhibited by tripterine with inhibition rates being 25.3%, 42.4% and 61.0% respectively. ATRA increased the adhesion between NB4 and HUVEC, which was reversed completely by tripterine. CONCLUSION: Tripterine can inhibit ATRA-caused adhesion between leukemia cells and endothelial cells, and it might be a potential agent for treating retinoic acid syndrome.
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Células Endoteliales/efectos de los fármacos , Tretinoina/farmacología , Triterpenos/farmacología , Adhesión Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Selectina E/biosíntesis , Células Endoteliales/citología , Células Endoteliales/metabolismo , Humanos , Molécula 1 de Adhesión Intercelular/biosíntesis , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patología , Triterpenos Pentacíclicos , Tripterygium/química , Molécula 1 de Adhesión Celular Vascular/biosíntesisRESUMEN
BACKGROUND: Gliomas are the most common type of primary brain tumour in the central nervous system of adults. The long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) is transcribed from the 5' tip of the HOXA locus. HOTTIP has recently been shown to be dysregulated and play an important role in the progression of several cancers. However, little is known about whether and how HOTTIP regulates glioma development. METHODS: In this study, we assayed the expression of HOTTIP in glioma tissue samples and glioma cell lines using real-time polymerase chain reaction and defined the biological functions of HOTTIP using the CCK-8 assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL assay) and tumour formation assay in a nude mouse model. Finally, we discovered the underlying mechanism using the Apoptosis PCR 384HT Array, Western blot, RNA immunoprecipitation (RIP) and luciferase reporter assay. RESULTS: HOTTIP was aberrantly down-regulated in glioma tissues and glioma cell lines (U87-MG, U118-MG, U251 and A172), and over-expression of HOTTIP inhibited the growth of glioma cell lines in vitro and in vivo. Furthermore, HOTTIP could directly bind to the brain and reproductive expression (BRE) gene and down-regulate BRE gene expression. In addition, we further verified that over-expression of the BRE gene promoted the growth of glioma cell lines in vitro. Finally, over-expression of HOTTIP significantly suppressed the expression of the cyclin A and CDK2 proteins and increased the expression of the P53 protein. However, we found that the over-expression of BRE significantly increased the expression of the cyclin A and CDK2 proteins and suppressed the expression of the P53 protein. Taken together, these findings suggested that high levels of HOTTIP reduced glioma cell growth. Additionally, the mechanism of HOTTIP-mediated reduction of glioma cell growth may involve the suppression of cyclin A and CDK2 protein expression, which increases P53 protein expression via the down-regulation of BRE. CONCLUSIONS: Our studies demonstrated that over-expression of HOTTIP promotes cell apoptosis and inhibits cell growth in U118-MG and U87-MG human glioma cell lines by down-regulating BRE expression to regulate the expression of P53, CDK2 and Cyclin A proteins. The data described in this study indicate that HOTTIP is an interesting candidate for further functional studies in glioma and demonstrate the potential application of HOTTIP in glioma therapy.
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Neoplasias Encefálicas/patología , Glioma/patología , Proteínas del Tejido Nervioso/genética , ARN Largo no Codificante/genética , Regulación hacia Arriba , Regiones no Traducidas 3' , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Ciclina A/metabolismo , Quinasa 2 Dependiente de la Ciclina/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Ratones , Trasplante de Neoplasias , Proteína p53 Supresora de Tumor/metabolismoAsunto(s)
Fracturas Óseas , Trastornos de la Motilidad Ocular , Humanos , Órbita , Estudios RetrospectivosRESUMEN
BACKGROUND: Non-small cell lung cancer (NSCLC) is a prolific and high-mortality disease with few effective treatments. Although the detection and surgical techniques for NSCLC continue to advance, the survival rate for the patients with NSCLC remains poor. Enhanced predictive biomarkers such as microRNAs (miRNAs) are needed at the time of diagnosis to better tailor therapies for patients. This study focused on the expression of miR-1280 in NSCLC tissues and distal normal tissues in order to explore the association between miR-1280 expression and NSCLC. METHODS: A total of 72 newly diagnosed primary NSCLC patients were enrolled in this study. Quantitative real-time polymerase chain reaction (PCR) was performed to identify the expression level of miR-1280 in the NSCLC tissues and distal normal tissues of these patients. RESULTS: The miR-1280 expression was significantly higher in the NSCLC tissues (0.084 ± 0.099) than distal normal tissues (0.014 ± 0.015, P = 0.009). In 54 patients (75%), the miR-1280 expression in the NSCLC tissues was upregulated (2-ΔΔct > 2), and no case showed a downregulation of miR-1280 expression. CONCLUSIONS: The expression level of miR-1280 could be regarded as a biomarker for NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Anciano , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia ArribaRESUMEN
[This corrects the article DOI: 10.1155/2014/621756.].