RESUMEN
Some microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression has been reported to correlate with chemoresistance of cancer cells. Therefore, the present study aims at investigating the effects of microRNA-139-5p (miR-139-5p) on cisplatin resistance of ovarian cancer (OC) with involvement of ring finger protein 2 (RNF2) and the mitogen-activated protein kinase (MAPK) signaling pathway. OC tissues were obtained from 66 primary OC patients. The cisplatin-sensitive A2780 and cisplatin-resistant A2780/DDP cell lines were collected for construction of RNF2 silencing and overexpressed plasmids. Cell vitality and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and annexin V-FITC/propidium iodide double-staining, respectively. Next, expression of RNF2, extracellular signal-related kinase, and p38 was determined by quantitative reverse transcription-quantitative polymerase chain reaction and Western blot analysis. Finally, the volume of xenograft tumors in BALB/c nude mice was detected. RNF2 and miR-139-5p were identified to be involved in OC. In addition, MAPK activation and RNF2 were related to cisplatin resistance of OC. miR-139-5p was downregulated in cisplatin-resistant OC tissues, and miR-139-5p overexpression could inhibit cell vitality, reduce cisplatin resistance, and promote apoptosis of OC cells. Furthermore, miR-139-5p combined with MAPK inhibitors more obviously reduced cisplatin resistance of OC. Taken together, this study demonstrated that miR-139-5p overexpression combined with inactivation of the MAPK signaling pathway can reverse the cisplatin resistance of OC by suppressing RNF2. Thus, miR-139-5p overexpression might be a future therapeutic strategy for OC.
Asunto(s)
Cisplatino/farmacología , Regulación hacia Abajo/genética , Resistencia a Antineoplásicos/genética , Sistema de Señalización de MAP Quinasas/genética , MicroARNs/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Animales , Apoptosis/genética , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Xenoinjertos , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Complejo Represivo Polycomb 1 , Transducción de Señal/genéticaRESUMEN
Cervical cancer (CC) remains a highly prevalent cancer and mortality globally among women globally. The aim of the present study was to assess the ability of miR-374b to regulate CC cells through JAM-2, whilst exploring whether the underlying mechanism and its relation to the p38/ERK signaling pathway. During the study, microRNA-374b (miR-374b) was observed to have been expressed at a low level among CC tissues. Hence, a series of miR-374b mimics, miR-374b inhibitors, siRNA against JAM-2, SB202190 (an inhibitor for p38), and PD98059 (an inhibitor for ERK) were introduced to treat CC Siha cells and normal cervical Ect1/E6E7 cells. MTT, flow cytometry, scratch test, and transwell assays were applied to determine cell viability, apoptosis, migration, and invasion. The inhibitory role of the p38/ERK signaling pathway was observed in the CC cells treated with miR-374b mimics or siRNA against JAM-2. miR-374b mimic exposure was found to reduce cell viability, migration, and invasion, but induce apoptosis. MiR-374b inhibitor exposure was observed to have induced effects on the CC cells in a contrary manner to those induced by that of the miR-374b mimics. The key findings of the study demonstrated that miR-374b significantly inhibits cell proliferation, migration, and invasion through the blockade of the p38/ERK signaling pathway activation, as well as negatively binding to JAM-2, highlighting its potential as a therapeutic target for CC.
Asunto(s)
Apoptosis/genética , Moléculas de Adhesión Celular/metabolismo , Sistema de Señalización de MAP Quinasas , MicroARNs/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Adulto , Secuencia de Bases , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica , Regulación hacia Arriba/genéticaRESUMEN
OBJECTIVE: To explore the potential correlation between apolipoprotein (Apo) levels and coronary atherosclerosis and investigate its predictive value for coronary artery lesions in asymptomatic population without diabetes. METHODS: We performed a retrospective analysis of data collected from 401 asymptomatic patients who took health check-ups. They were divided into atherosclerosis group (n=224)and control group (n=177) based on the outcome of CT angiography and blood biochemical findings. The risk factors, lipid profiles, and Apo levels were compared between these two groups. The best biochemical indicators for predicting the coronary atherosclerosis were explored. RESULTS: The levels of ApoB, ApoC2,ApoC3,and ApoE and ApoB/ApoA1 ratio were significantly higher in the atherosclerosis group than in the control group (all P<0.01), whereas the ApoA1,ApoA2, and lipoprotein a levels showed no such significant difference (all P>0.05). Logistic regression analysis revealed that age, male, hypertension,ApoC3(OR=1.572,95%CI 1.200-2.061) and ApoB/ApoA1 ratio (OR=1.767,95% CI 1.335-2.338) were independently correlated with coronary atherosclerosis (all P<0.01). In the prediction of the presence of plaque, ApoB had the largest area under curves, and the optimal cutoff point was 1.005 g/L. CONCLUSIONS: ApoC3 is closely associated with subclinical coronary atherosclerosis,while the decrease of ApoA1 level is not obvious during this period. Compared with other lipid indicators, ApoB is the strongest predictor for coronary atherosclerosis in asymptomatic non-diabetic population.
Asunto(s)
Aterosclerosis , Enfermedad Coronaria , Angiografía , Apolipoproteínas , Diabetes Mellitus , Humanos , Hipertensión , Lipoproteína(a) , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To explore the potential correlation between creatine kinase and the long-term patency of coronary drug eluting stents. METHODS: The clinical data of 74 patients who had undergone coronary computed tomography angiography after drug eluting stents implantation were retrospecpectively analyzed. Based on the computed tomography angiography findings,these patients were divided into patency group and non-patency group. The mean follow-up time was (20.5 ± 13.1) months. The serum levels of creatine kinase and creatine kinase isoenzyme were measured to determine the relationship of stent patency with these oxidative-related biomarkers after long-term follow-up. The T test or non-parametric test was adopted to compare the intergroup difference of measurement data,whereas chi-square test was conducted to test the difference of enumeration data. Logistic regression was adopted to analyze the biochemical indexes and clinical information. Only variables with a P value of less than 0.05 in the univariable analyses entered the multivariate Logistic regression model. RESULTS: Patients in the non-patency group had significantly higher serum creatine kinase level compared with patients in patency group [(115.5 ± 51.5)U/L vs.(75.9 ± 29.4)U/L, P=0.012] and significantly higher level of creatine kinase isoenzyme [(3.5 ± 5.3)U/L vs.(1.7 ± 1.3)U/L,P=0.034]. Furthermore,the Logistic analysis showed that serum creatine kinase level (odds ratio=1.573,95% CI=1.022-2.421, P=0.039)was an independent predictor of stent patency. CONCLUSION: Creatine kinase is an independent risk factor associated with stent non-patency.
Asunto(s)
Angiografía Coronaria , Distribución de Chi-Cuadrado , Creatina Quinasa , Stents Liberadores de Fármacos , Humanos , Modelos Logísticos , Factores de Riesgo , Tomografía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To discuss the correlation of pathologic subtypes and immunohistochemical implication with CT features of lung adenocarcinoma 1 cm or less in diameter with focal ground-glass opacity (fGGO). METHODS: CT appearances of 59 patients who underwent curative resection of lung adenocarcinoma ≤ 1 cm with fGGO were analyzed in terms of lesion location, size, density, shape (round, oval, polygonal, irregular), margin (smooth, lobular, spiculated, lobular and spiculated), bubble-like sign, air bronchogram, pleural tag, and tumor-lung interface. Histopathologic subtypes were classified according to International Association for the Study of Lung Cancer/ American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma. Common molecular markers in immunohistochemical study included human epidermal growth factor receptor (HER)-1,HER-2,Ki-67, vascular endothelial growth factor (VEGF) and DNA topoisomerase 2Α.Patients' age and lesions' size and density were compared with pathologic subtypes using analysis of variance or nonparametric Wilcoxon tests. Patients' gender, lesion location, shape and margin, bubble-like sign, air bronchogram, pleural tag, and tumor-lung interface were compared with histopathologic subtypes and immunohistochemical implication using ψ² test or Fisher's exact test. RESULTS: The patients' gender, age, lesion location, shape, air bronchogram, pleural tag, and tumor-lung interface were not significantly different among different histopathologic subtypes (P=0.194, 0.126, 0.609, 0.678, 0.091, 0.374, and 0.339, respectively), whereas the lesion size,density,bubble-like sign, and margin showed significant differences (P=0.028, 0.002, 0.003, 0.046, respectively). The expression of Ki-67 significantly differed among nodules with different shapes(P=0.015). Statistically significant difference also existed between tumor-lung interface and HER-1 expression (P=0.019) and between bubble sign and HER-2 expression (P=0.049). CONCLUSIONS: Of lung adenocarcinoma ≤ 1 cm with fGGO,bubble-like sign occurs more frequently in invasive pulmonary adenocarcinoma and less frequently in atypical adenomatous hyperplasia. In addition, preinvasive lesions (atypical adenomatous hyperplasia and adenocarcinoma in situ) more frequently demonstrates smooth margin,while invasive lesions (minimally invasive adenocarcinoma and invasive pulmonary adenocarcinoma) more frequently demonstrates lobular and spiculated margin. Some CT features are associated with immunohistochemical implication of lung adenocarcinoma ≤ 1 cm with fGGO.
Asunto(s)
Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma del Pulmón , Humanos , Hiperplasia , Pulmón , Factor A de Crecimiento Endotelial VascularRESUMEN
Blood-brain barrier (BBB) disruption occurring within the first few hours of ischemic stroke onset is closely associated with hemorrhagic transformation following thrombolytic therapy. However, the mechanism of this acute BBB disruption remains unclear. In the neurovascular unit, neurons do not have direct contact with the endothelial barrier; however, they are highly sensitive and vulnerable to ischemic injury, and may act as the initiator for disrupting BBB when cerebral ischemia occurs. Herein, we employed oxygen-glucose deprivation (OGD) and an in vitro BBB system consisting of brain microvascular cells and astrocytes to test this hypothesis. Neurons (CATH.a cells) were exposed to OGD for 3-h before co-culturing with endothelial monolayer (bEnd 3 cells), or endothelial cells plus astrocytes (C8-D1A cells). Incubation of OGD-treated neurons with endothelial monolayer alone did not increase endothelial permeability. However, when astrocytes were present, the endothelial permeability was significantly increased, which was accompanied by loss of occludin and claudin-5 proteins as well as increased vascular endothelial growth factor (VEGF) secretion into the conditioned medium. Importantly, all these changes were abolished when VEGF was knocked down in astrocytes by siRNA. Our findings suggest that ischemic neurons activate astrocytes to increase VEGF production, which in turn induces endothelial barrier disruption.
Asunto(s)
Astrocitos/metabolismo , Barrera Hematoencefálica/metabolismo , Endotelio Vascular/metabolismo , Neuronas/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Barrera Hematoencefálica/citología , Hipoxia de la Célula/fisiología , Células Cultivadas , Técnicas de Cocultivo , Endotelio Vascular/citología , Glucosa/deficiencia , Humanos , Oxígeno/metabolismoRESUMEN
OBJECTIVE: To assess the value of preoperative coronary computed tomographic angiography (CCTA) in the detection of coronary artery disease (CAD) in patients planned to undergo non-cardiac surgery at intermediate or high risk to avoid unnecessary invasive coronary angiography (ICA). METHODS: The study protocol was approved by our institutional review board and informed consent was given. In this prospective study, 157 consecutive patients who underwent CCTA before undergoing non-cardiac surgery at intermediate or high risk was involved. The non-cardiac surgery included high-risk surgery (17 patients) and intermediate-risk surgery (140 patients). Follow-up was performed in 6-11 months to define cardiac events described as acute coronary syndrome (ACS) or death secondary to ASC, arrhythmias, cardiac revascularization, or cardiac failure. χ(2) test was performed to compare the differences in incidence of cardiac events among patients who had undergone or who had not undergone preoperative ICA. RESULTS: CCTA was of diagnostic value in 145 of 157 patients. Thirty-seven of 145 had no CAD, and 88 of 145 had no significant CAD (<50% stenosis), and non-cardiac surgery was performed in them without preoperative ICA. No patients in those patients had postoperative ischemic events at follow-up; 20 had significant CAD (≥50% stenosis) and underwent surgery after preoperative ICA. CCTA was non-diagnostic in 12 patients who were referred for preoperative ICA, and 4 of 12 underwent surgery after PCI or CABG. There were no differences in cardiac events between patients who had undergone preoperative ICA and those who had not (P=0.45). CONCLUSIONS: In patients with planned non-cardiac surgery at medium or high risk of cardiovascular events, preoperative CCTA is an effective diagnostic tool for detecting CAD. Preoperative ICA can be safely avoided in patients with normal findings or with stenosis<50% in CCTA.
Asunto(s)
Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tomografía Computarizada Espiral/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Perioperativa , Estudios ProspectivosRESUMEN
Ginseng, a highly esteemed herbal medicine, has been utilized over 5000 years, predominantly in Far Eastern countries. Ginseng is categorized into garden ginseng (GG) and ginseng under forest (FG). However, in contrast to FG, excessive intake of GG may lead to potential adverse effects due to disruption of epithelial cell integrity, and the specific population groups that may be at higher risk. In this work, untargeted metabolomics were used to determine the heterogeneity between GG and FG, the data indicates that the content of Ethyl caffeate, Homoorientin, Citric acid and Quinic acid in GG were higher than in FG. Mass spectrometry imaging showed that ethyl caffeate and Homoorientin were concentrated on the brownish yellow exocarp of the primary root. Our experiments demonstrated that excessive exposure to ethyl caffeate and Homoorientin exacerbated the inflammatory response of HUVECs and reduced the expression of cell junctions. This suggest that the compounds causing adverse effects from excessive intake of GG are mainly concentrated in the yellow exocarp of the primary root of GG. These results suggest that untargeted metabolomics coupled with MALDI-MSI can visualize the spatial distribution of endogenous differential molecules of the same herb in different growth environments or developmental stages.
RESUMEN
In order to reduce the errors of near-infrared spectral acquisition, analytical models of coal spectra with different particle sizes, 0.2, 1, 3 and 13 mm, were studied in this paper. The feature information of spectra was extracted by PCA method, then two quantitative analytical models were established based on GA-BP and GA-Elman neural network algorithms. Through spectral preprocessing with data normalization and multiplicative scatter correction methods, the results showed that with the 0.2 mm size, the correlations between spectra and the standard value were the strongest, and the analytical precision of models were the best. But for smoothed spectra, the models, under 1 mm size, were better than others. Smoothing method was not suitable for the spectra with less obvious wave crest characteristics, while multiplicative scatter correction method was better. According to original spectra, particle size of 0.2 mm had the highest accuracy, followed by 1 and 3 mm and the worst was under 13 mm. Overall, the larger the size for coal particle, the more the unstable factors for spectra, increasing negative influences on analytical models.
RESUMEN
Reactive oxygen species (ROS) can induce oxidative injury and are generally regarded as toxic byproducts, although they are increasingly recognized for their signaling functions. Increased ROS often accompanies liver regeneration (LR) after liver injuries, however, their role in LR and the underlying mechanism remains unclear. Here, by employing a mouse LR model of partial hepatectomy (PHx), we found that PHx induced rapid increases of mitochondrial hydrogen peroxide (H2O2) and intracellular H2O2 at an early stage, using a mitochondria-specific probe. Scavenging mitochondrial H2O2 in mice with liver-specific overexpression of mitochondria-targeted catalase (mCAT) decreased intracellular H2O2 and compromised LR, while NADPH oxidases (NOXs) inhibition did not affect intracellular H2O2 or LR, indicating that mitochondria-derived H2O2 played an essential role in LR after PHx. Furthermore, pharmacological activation of FoxO3a impaired the H2O2-triggered LR, while liver-specific knockdown of FoxO3a by CRISPR-Cas9 technology almost abolished the inhibition of LR by overexpression of mCAT, demonstrating that FoxO3a signaling pathway mediated mitochondria-derived H2O2 triggered LR after PHx. Our findings uncover the beneficial roles of mitochondrial H2O2 and the redox-regulated underlying mechanisms during LR, which shed light on potential therapeutic interventions for LR-related liver injury. Importantly, these findings also indicate that improper antioxidative intervention might impair LR and delay the recovery of LR-related diseases in clinics.
Asunto(s)
Hepatectomía , Regeneración Hepática , Animales , Ratones , Modelos Animales de Enfermedad , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/metabolismo , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
Asymmetric functionalization of alkenes allows the direct synthesis of a wide range of chiral compounds. Vicinal hydroxyazidation of alkenes provides a desirable path to 1,2-azidoalcohols; however, existing methods are limited by the control of stereoselectivity and regioselectivity. Herein, we describe a dual-enzyme cascade strategy for regiodivergent and stereoselective hydroxyazidation of alkenes, affording various enantiomerically pure 1,2-azidoalcohols. The biocatalytic cascade process is designed by combining styrene monooxygenase-catalyzed asymmetric epoxidation of alkenes and halohydrin dehalogenase-catalyzed regioselective ring opening of epoxides with azide. Additionally, a one-pot chemo-enzymatic route to chiral ß-hydroxytriazoles from alkenes is developed via combining the biocatalytic cascades and Cu-catalyzed azide-alkyne cycloaddition.
RESUMEN
Phosgene is a toxic gas that is widely used in modern industry, and its inhalation can cause severe pulmonary edema. There is no effective clinical treatment because the mechanism of phosgene-induced pulmonary edema still remains unclear. Many studies have demonstrated that the Na(+)/K(+)-ATPase plays a critical role in clearing pulmonary edema and the inhibition of Na(+)/K(+)-ATPase protein expression has been found in many other pulmonary edema models. In the present study, after the mice were exposed to phosgene, there was serious pulmonary edema, indicating the dysfunction of the ATPases in mice. However, in vitro enzyme study showed that there were increases in the activities of the Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Further investigation showed that the ATP content and mitochondrial respiratory control ratio (RCR) in the lungs decreased significantly. The oxidative stress product, malondialdehyde (MDA), increased while the antioxidants (GSH, SOD, and TAC) decreased significantly. These results indicate that mitochondrial respiration is the target of phosgene. The dysfunction of ATPases due to impaired mitochondrial respiration may be a new mechanism of phosgene-induced pulmonary edema.
Asunto(s)
Adenosina Trifosfatasas/metabolismo , Respiración de la Célula/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosgeno/toxicidad , Edema Pulmonar/inducido químicamente , Edema Pulmonar/metabolismo , Animales , Antioxidantes/farmacología , Respiración de la Célula/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Estrés Oxidativo/fisiología , Edema Pulmonar/patología , Factores de TiempoRESUMEN
Blood-brain barrier (BBB) opening occurs under many physiological and pathological conditions. BBB opening will lead to the leakage of large circulating molecules into the brain parenchyma. These invasive molecules will induce immune responses. Microglia and astrocytes are the two major cell types responsible for immune responses in the brain, and Fc gamma receptor I (FcgammaRI) and Toll-like receptor 4 (TLR4) are the two important receptors mediating these processes. Data suggest that activation of the FcgammaRI pathway mediates antiinflammatory processes, whereas activation of TLR4 pathway leads to proinflammatory activities. In the present study, we tested the hypothesis that BBB opening could lead to alterations in FcgammaRI and TLR4 pathways in microglia and astrocytes, thus limiting excessive inflammation in the brain. The transient BBB opening was induced by adrenaline injection through a caudal vein in Sprague-Dawley rats. We found that the FcgammaRI pathway was significantly activated in both microglia and astrocytes, as exhibited by the up-regulation of FcgammaRI and its key downstream molecule Syk, as well as the increased production of the effector cytokines, interleukin (IL)-10 and IL-4. Interestingly, after transient BBB opening, TLR4 expression was also increased. However, the expression of MyD88, the central adapter of the TLR4 pathway, was significantly inhibited, with decreased production of the effector cytokines IL-12a and IL-1beta. These results indicate that, after transient BBB opening, FcgammaRI-mediated antiinflammatory processes were activated, whereas TLR4-mediated proinflammatory activities were inhibited in microglia and astrocytes. This may represent an important neuroprotective mechanism of microglia and astrocytes that limits excessive inflammation after BBB opening.
Asunto(s)
Barrera Hematoencefálica/inmunología , Encefalitis/inmunología , Gliosis/inmunología , Neuroglía/inmunología , Receptores de IgG/inmunología , Receptor Toll-Like 4/inmunología , Animales , Astrocitos/inmunología , Astrocitos/metabolismo , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/fisiopatología , Citocinas/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/inmunología , Encefalitis/metabolismo , Encefalitis/fisiopatología , Epinefrina/farmacología , Gliosis/metabolismo , Gliosis/fisiopatología , Tolerancia Inmunológica/inmunología , Péptidos y Proteínas de Señalización Intracelular/inmunología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Microglía/inmunología , Microglía/metabolismo , Factor 88 de Diferenciación Mieloide/inmunología , Factor 88 de Diferenciación Mieloide/metabolismo , Neuroglía/citología , Neuroglía/metabolismo , Proteínas Tirosina Quinasas/inmunología , Proteínas Tirosina Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de IgG/metabolismo , Transducción de Señal/inmunología , Quinasa Syk , Receptor Toll-Like 4/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/inmunología , Vasoconstrictores/farmacologíaRESUMEN
OBJECTIVE: To investigate the feasibility of low-tube-voltage (80 kVp) coronary CT angiography (CCTA) combined with contrast medium (CM) reduction and iterative model reconstruction (IMR) on patients with standard body mass index compared with clinical routine protocol. METHODS: Retrospectively gated helical CCTA scans were acquired using a 256-slice multi-slice CT (Brilliance iCT; Philips Healthcare, Cleveland, OH) on 94 patients with standard body mass index (20-25 kg m(-2)) who were randomly assigned into 2 groups. The scan protocol for Group 1 was 100 kVp and 600 mAs with 70 ml CM at an injection rate of 4.5-5.5 ml s(-1); images were reconstructed by a hybrid iterative reconstruction technique (iDose(4); Philips Healthcare). Group 2 was scanned at 80 kVp and 600 mAs with 35 ml CM at an injection rate of 3.5-4.5 ml s(-1); images were reconstructed with IMR. Objective measurements such as the mean image noise and contrast-to-noise ratio of the two groups were measured on CT images and compared using the paired t-test. In addition, a subjective image quality evaluation was performed by two radiologists who were blinded to the scan protocol, using a 5-point scale [1 (poor) to 5 (excellent)]. The results of the two groups were compared using Mann-Whitney U test. RESULTS: The iodine delivery rate of Group 2 was 1.0 ± 0.5 gI s(-1) compared with 2.1 ± 0.5 gI s(-1) in Group 1 resulting in a reduction of 52.4%. In addition, an effective radiation dose reduction of 56.4% was achieved in Group 2 (2.4 ± 1.2 mSv) compared with Group 1 (5.5 ± 1.4 mSv). The mean CT attenuation, contrast-to-noise ratio and image quality of all segments in Group 2 were significantly improved compared with those in Group 1 (all, p < 0.01). CONCLUSION: The use of IMR along with a low tube voltage (80 kVp) combined with a low CM protocol for CCTA can reduce both radiation and CM dose with improved image quality. ADVANCES IN KNOWLEDGE: In this study, we used a novel knowledge-based IMR which remarkably reduced the image noise. We compared the quality of the images obtained when the tube voltage was reduced to 80 kVp and that of those obtained according to the clinical routine protocols to determine whether ultra-low-dose imaging plus IMR is feasible in CCTA scans. We found that a low dose protocol combined with 80 kVp and reduced CM for CCTA can reduce both radiation dose and CM dose with improved image quality by the use of IMR in non-obese patients.
Asunto(s)
Índice de Masa Corporal , Angiografía Coronaria/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Técnicas de Imagen Sincronizada Cardíacas , Medios de Contraste/administración & dosificación , Estudios de Factibilidad , Femenino , Humanos , Masculino , Estudios Prospectivos , Dosis de Radiación , Tomografía Computarizada por Rayos X/instrumentaciónRESUMEN
Glycoprotein nonmetastatic melanoma B (GPNMB) is a type I transmembrane glycoprotein which is overexpressed in many tumors and seems to play a critical role in metastasis of malignant tumors. The purpose of this study was to determine GPNMB expression in small cell lung cancer (SCLC) and analyze the prognostic value in patients with SCLC. A total of 132 cases of SCLCs were analyzed immunohistochemically on tissue microarrays (TMAs). Patients were divided into weak-positive and strong-positive GPNMB groups. In addition, serum GPNMB was evaluated by enzyme-linked immunosorbent assay (ELISA). The average serum GPNMB concentration was 1054.15 ± 363.71 pg/mL in the weak-positive group, 2611.52 ± 457.57 pg/mL in the strong-positive group, and 427.61 ± 273.9 pg/mL in the control. The strong-positive group showed significantly higher serum GPNMB levels than the weak-positive group and healthy control (p < 0.01). Overall survival in the weak-positive GPNMB group was significantly longer than in the strong-positive group (27 months vs 15 months, p < 0.01). These results suggest that the expression of GPNMB may be useful as a prognostic indicator in patients with SCLC.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Glicoproteínas de Membrana/sangre , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/genética , Adulto , Anciano , Anciano de 80 o más Años , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Pronóstico , Análisis de Matrices TisularesRESUMEN
Reactive oxygen species (ROS) are closely related to the aging process. In our previous studies, we found that the saponins from Aralia taibaiensis have potent antioxidant activity, suggesting the potential protective activity on the aging. However, the protective effect of the saponins and the possible underlying molecular mechanism remain unknown. In the present study, we employed a D-galactose-induced aging rat model to investigate the protective effect of the saponins. We found that D-galactose treatment induced obvious aging-related changes such as the decreased thymus and spleen coefficients, the increased advanced glycation end products (AGEs) level, senescence-associated ß-galactosidase (SAß-gal) activity, and malondialdehyde (MDA) level. Further results showed that Forkhead box O3a (FOXO3a), nuclear factor-erythroid 2-related factor 2 (Nrf2), and their targeted antioxidants such as superoxide dismutase 2 (SOD2), catalase (CAT), glutathione reductase (GR), glutathione (GSH), glutamate-cysteine ligase (GCL), and heme oxygenase 1 (HO-1) were all inhibited in the aging rats induced by D-galactose treatment. Saponins supplementation showed effective protection on these changes. These results demonstrate that saponins from Aralia taibaiensis attenuate the D-galactose-induced rat aging. By activating FOXO3a and Nrf2 pathways, saponins increase their downstream multiple antioxidants expression and function, at least in part contributing to the protection on the D-galactose-induced aging in rats.
Asunto(s)
Envejecimiento/efectos de los fármacos , Aralia/química , Factores de Transcripción Forkhead/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Saponinas/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Proteína Forkhead Box O3 , Galactosa , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Bazo/efectos de los fármacos , Bazo/patología , Timo/efectos de los fármacos , Timo/patologíaRESUMEN
Arsenic exposure has been shown to induce hypoxia inducible factor 1α (HIF-1α) accumulation, however the underlying mechanism remains unknown. In the present study, we tested the hypothesis that arsenic exposure triggered the interaction between NADPH oxidase and mitochondria to promote reactive oxygen species (ROS) production, which inactivate prolyl hydroxylases (PHDs) activity, leading to the stabilization of HIF-1α protein. Exposure of human immortalized liver cell line HL-7702 cells to arsenite induced HIF-1α accumulation in a dose-dependent manner, which was abolished by SOD mimetic MnTMPyP. Inhibition of NADPH oxidase with diphenyleneiodonium chloride (DPI) or inhibition of mitochondrial respiratory chain with rotenone significantly blocked arsenite-induced ROS production, and the mitochondria appeared to be the major source of ROS production. Arsenite treatment inhibited HIF-1α hydroxylation by prolyl hydroxylases (PHDs) and increased HIF-1α stabilization, but did not affect HIF-1α mRNA expression and Akt activation. Supplementation of ascorbate or Fe(II) completely abolished arsenite-induced PHDs inhibition and HIF-1α stabilization. In conclusion, these results define a unique mechanism of HIF-1α accumulation following arsenic exposure, that is, arsenic activates NADPH oxidase-mitochondria axis to produce ROS, which deplete intracellular ascorbate and Fe(II) to inactivate PHDs, leading to HIF-1α stabilization.
Asunto(s)
Arsenitos/toxicidad , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Mitocondrias/fisiología , NADPH Oxidasas/fisiología , Inhibidores de Prolil-Hidroxilasa/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Células Cultivadas , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/químicaRESUMEN
Human arsenic exposure is associated with increased risk of skin cancer, and arsenite greatly enhances ultraviolet (UV)-induced skin tumors in a mouse model of carcinogenesis. Inhibition of DNA repair is one proposed mechanism for the observed cocarcinogenicity. We have previously demonstrated that low concentrations of arsenite inhibit poly(ADP-ribose) polymerase (PARP)-1, thus interfering with DNA repair process triggered by UV radiation. Because overactivation of PARP-1 often leads to apoptotic cell death, and unrepaired DNA lesions promote genomic instability and carcinogenesis, we hypothesized that inhibition of PARP-1 by arsenic may promote the survival of potentially "initiated carcinogenic cells," i.e., cells with unrepaired DNA lesions. In the present study, we tested this hypothesis on UV-challenged HaCat cells. Cells were pretreated with 2µM arsenite for 24 h before UV exposure. Outcome parameters included apoptotic death rate, PARP-1 activation, apoptotic molecules, and retention of DNA lesions. UV exposure induced PARP-1 activation and associated poly(ADP-ribose) production, apoptosis-inducing factor release, cytochrome C release, and caspases activation, which led to apoptotic death in HaCat cells. Pretreatment with 2µM arsenite significantly inhibited UV-induced cell death as well as the associated molecular events. Notably, knockdown of PARP-1 with small interfering RNA completely abolished the antagonism of arsenite. Furthermore, arsenite pretreatment led to long-term retention of UV-induced cyclobutane pyrimidine dimers. Together, these results suggest that low concentration of arsenite reduces UV-induced apoptosis via inhibiting PARP-1, thus promoting the survival of cells with unrepaired DNA lesions, which may be an important mechanism underlying arsenic cocarcinogenic action.
Asunto(s)
Arsenitos/toxicidad , Daño del ADN/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Inhibidores Enzimáticos/toxicidad , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Rayos Ultravioleta/efectos adversos , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Inhibidores de Caspasas , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/efectos de la radiación , Poli(ADP-Ribosa) Polimerasa-1 , Efectos de la RadiaciónRESUMEN
BACKGROUND: Perceptions of exercise benefits and barriers affect exercise behavior. Because of the clinical course and treatment, dialysis patients differ from the general population in their perceptions of exercise benefits and barriers, especially the latter. At present, no valid instruments for assessing perceived exercise benefits and barriers in dialysis patients are available. OBJECTIVES: Our goal was to develop and test the psychometric properties of the Dialysis patient-perceived Exercise Benefits and Barriers Scale (DPEBBS). METHODS: A literature review and two focus groups were conducted to generate the initial item pool. An expert panel examined the content validity. Then, 269 Chinese hemodialysis patients were recruited by convenience sampling. Exploratory and confirmatory factor analyses were used to test construct validity. Finally, internal consistency and test-retest reliability were assessed. RESULTS: The expert panel determined that the content validity index was satisfactory. The final 24-item scale consisted of six factors explaining 57% of the total variance in the data. Confirmative factor analysis supported the six-factor structure and a higher-order model. Cronbach's alpha was 0.87 for the total scale, and 0.84 for test-retest reliability. CONCLUSION: The DPEBBS was a valid and reliable instrument for evaluating dialysis patients' perceived benefits and barriers to exercise. The application value of this scale remains to be investigated by increasing the sample size and evaluating patients undergoing different dialysis modalities and coming from different regions and cultural backgrounds.
Asunto(s)
Ejercicio Físico/psicología , Psicometría/métodos , Diálisis Renal/psicología , Anciano , China , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Two new compounds, named as sonchifolactone E (1) and sonchifolinin B (2), have been isolated from the whole plant of Ixeris sonchifolia, along with one known compound, sonchifolatone A (3). Their structures and stereochemistry were determined by spectroscopic methods.