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In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.
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BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating autoimmune disease that affects the central nervous system. It typically manifests as optic neuritis or extensive longitudinal myelitis, with or without the presence of anti-aquaporin protein 4 autoantibodies (immunoglobulin G). CASE SUMMARY: We report the case of a 45-year-old woman with a history of Sjogren's syndrome who was diagnosed with NMOSD accompanied by spinal cord injury and left calf intermuscular vein thrombosis. The patient received hormone shock and gamma globulin therapy in the acute phase and standard rehabilitation treatment during convalescence. Upon discharge, the patient was able to control urination and defecation, stand independently, and walk short distances with the aid of a walker. CONCLUSION: This case suggests that pharmacotherapy and standard rehabilitation treatment can improve the prognosis of NMSOD patients.
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The bioinspired synthesis of heterodimer neolignan analogs is reported by single-electron oxidation of both alkenyl phenols and phenols individually, followed by a combination of the resultant radicals. This oxidative radical cross-coupling strategy can afford heterodimer 8-5' or 8-O-4' neolignan analogs selectively with the use of air as the terminal oxidant and copper acetate as the catalyst at room temperature.
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Cobre/química , Lignanos/síntesis química , Fenoles/química , Catálisis , Lignanos/química , Estructura Molecular , Oxidantes , Oxidación-ReducciónRESUMEN
In this study, the ZnO quantum dots (QDs) water-based fluorescent anti-counterfeiting ink was prepared with the polyvinylpyrrolidone (PVP) content of 0.15-0.17 g/mL, the ZnO QDs concentration of 4% and water as the solvent, which has good fluorescence, printability and resistance. According to the halftone technology, fluorescence quenching of the ZnO QDs by acid, and acid resistance of the organic fluorescent ink, a high-quality anti-counterfeiting method of fluorescent discoloration was proposed. The QDs ink has broad application prospects in the field of anti-counterfeiting green packaging.
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Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become a standard therapy for non-small cell lung cancer (NSCLC) patients with sensitive mutations. However, acquired resistance inevitably emerges after a median of 6-12 months. It has been demonstrated that autophagy plays an important role in EGFR-TKI resistance. 20(S)-ginsenoside Rg3 (Rg3) is proposed to sensitize the cancer cells to chemotherapy by inhibiting autophagy. We examined the ability of Rg3 to inhibit autophagy and increase the sensitivity of NSCLC cells to icotinib. We show that the induction of autophagy in response to icotinib contributes to the development of icotinib resistance. Rg3 is capable of inhibiting autophagic flux and enhancing the sensitivity of NSCLC cells to icotinib. The resistance to icotinib could also be reversed through Rg3-induced autophagy inhibition. Autophagy inhibition by Rg3 increases the therapeutic response in both icotinib-sensitive and icotinib-resistant NSCLC cells with an EGFR-activating mutation and may be an effective new treatment strategy for this disease.
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Autofagia/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/patología , Éteres Corona/farmacología , Ginsenósidos/farmacología , Neoplasias Pulmonares/patología , Quinazolinas/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: To establish the regional lymph node (LN) distribution probability map and draw the neck clinical target volume specific to nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: One thousand patients with pathologically proven NPC were enrolled from January 2010 to December 2011. The center point of the LNs with a minimal axial diameter of ≥4 mm was marked on a single treatment planning computed tomography scan. The neck LN levels I to X using the 2013 updated international consensus guidelines were also contoured. LN distribution probability maps and distribution curves were established. The relationships between the LN distribution and consensus guidelines were analyzed to propose modifications for clinical target volume boundaries specific to NPC. RESULTS: A total of 10,651 LNs from 959 patients were marked. Based on the distribution of LNs and consensus guidelines, most of the LN levels defined in the 2013 updated consensus guidelines were confirmed to be comprehensive and applicable for NPC. However, for level Vb, 13.3% of cases (11 of 83) had LNs beyond the posteromedial border. For level VIIa (retropharyngeal LN), 1.5% of cases (12 of 819) had LNs above the cranial boundary, and 5 cases had LNs that emerged in the medial group. Moreover, we confirmed that no LN had been detected in certain areas of levels Ib, II, IVa, and Vc. Accordingly, a new level VIIc was proposed to include the medial group of retropharyngeal LNs, moderately extended boundaries for levels Vb and VIIa were recommended, and reduced boundaries are possibly adaptable for levels Ib, II, IV, and Vc. CONCLUSIONS: Most LN levels in the 2013 updated consensus guidelines are comprehensive and applicable for NPC. We have proposed a new level VIIc to include a medial group of retropharyngeal LNs, recommended moderate extended boundaries for levels Vb and VIIa, and suggested that the boundaries for levels Ib, II, IV, and Vc might be reduced.
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Consenso , Ganglios Linfáticos/diagnóstico por imagen , Linfografía/normas , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Guías de Práctica Clínica como Asunto , Tomografía Computarizada por Rayos X , Adulto , Anciano , Femenino , Humanos , Linfografía/métodos , Masculino , Persona de Mediana Edad , Cuello/diagnóstico por imagen , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
OBJECTIVES: To clarify the incidence of brainstem toxicity and perform a dose-volume analysis for the brainstem after long-term follow-up of a large cohort of nasopharyngeal carcinoma (NPC) patients who underwent intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: All patients with NPC treated with IMRT at Sun Yat-sen University Cancer Center between April 2009 and March 2012 were retrospectively reviewed. A total of 1544 patients with follow-up >12months and detailed treatment plan data were included. Radiotherapy was administered using the simultaneous integrated boost technique in 2.0-2.48Gy per fractions/28-33 fractions. Brainstem necrosis was defined as lesions with high signal intensity on T2-weighted images and low signal intensity on T1-weighted images, with or without enhancement after administration of contrast in follow-up MRI. RESULTS: After median follow-up of 79.7months (range, 12.2-85.6months), 2/1544 (0.13%) patients developed brainstem necrosis after intervals of 12.3 and 18.5months. Actuarial incidence of brainstem necrosis was 0.07%, 0.13%, 0.13% and 0.13% after 1, 2, 3 and 5years, respectively. Overall, 384 (24.9%), 153 (9.9%), 67 (4.3%), 39 (2.5%), 78 (5.1%), and 114 (7.4%) patients had excessive doses of Dmax≥64Gy, D1cc>59Gy, D2cc>59Gy, aV50>5.9cc, aV55>2.7cc and aV60>0.9cc respectively, of whom only two developed brainstem necrosis. CONCLUSIONS: Brainstem necrosis is rare in NPC. The definitive criteria based on conventional radiotherapy cannot accurately predict the occurrence of brainstem necrosis after IMRT, thus more flexible definitive criteria with strict restrictions need to be defined.
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Tronco Encefálico/efectos de la radiación , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidad Modulada/efectos adversos , Adolescente , Adulto , Anciano , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/patología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/diagnóstico por imagen , Necrosis , Dosificación Radioterapéutica , Adulto JovenRESUMEN
To determine the potential effects of seasonal changes on water temperature and water quality upon removal of ammonium and organic carbon pollutants and to characterize the variations in microbial characteristics, a pilot-scale activated carbon filter biologically enhanced with heterotrophic nitrifying bacteria was investigated for 528 days. The results show that 69.2 ± 28.6% of ammonium and 23.1 ± 11.6% of the dissolved organic carbon were removed by the biologically enhanced activated carbon (BEAC) reactor. It is shown that higher biodegradable dissolved organic carbon enhances ammonium removal, even at low temperatures. The C/N ratio consumed by the BEAC reactor reached a steady value (i.e., 3.3) after 2 months of operation. Despite seasonal fluctuations and competition of the indigenous community, the heterotrophic nitrifying bacteria (Acinetobacter sp. HRBLi 16 and Acinetobacter harbinensis strain HITLi 7) remained relatively stable. The amount of carbon source was the most significant environmental parameter and dramatically affected the microbial community compositions in the BEAC reactor. The present study provides new insights into the application of a BEAC reactor for ammonium removal from drinking water, resisting strong seasonal changes.
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Acinetobacter/metabolismo , Compuestos de Amonio/análisis , Carbón Orgánico/química , Agua Potable/química , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Reactores Biológicos/microbiología , China , Agua Potable/normas , Filtración , Procesos Heterotróficos , Estaciones del Año , Calidad del AguaRESUMEN
BACKGROUND: The E-26 transformation-specific related gene (ERG) is frequently expressed in cytogenetically normal acute myeloid leukemia (CN-AML). Herein, we performed a meta-analysis to investigate the relationship between the prognostic significance of ERG expression and CN-AML. METHODS: A systematic review of PubMed database and other search engines were used to identify the studies between January 2005 and November 2016. A total of 667 CN-AML patients were collected from seven published studies. Of the 667 patients underwent intensive chemotherapy, 429 had low expression of ERG and 238 had high expression of ERG. Summary odds ratio (OR) and the 95% confidence interval (CI) for the ERG expression and CN-AML were calculated using fixed- or random-effects models. Heterogeneity was assessed using Chi-squared-based Q- statistic test and I2 statistics. All statistical analyses were performed using R.3.3.1 software packages (R Foundation for Statistical Computing, Vienna, Austria) and RevMan5.3 (Cochrane Collaboration, Copenhagen, Denmark). RESULTS: Overall, patients with high ERG expression had a worse relapse (OR = 2.5127, 95% CI: 1.5177-4.1601, P = 0.0003) and lower complete remission (OR = 0. 3495, 95% CI: 0.2418-0.5051, P< 0.0001). With regard to the known molecular markers, both internal tandem duplications of the fms-related tyrosine kinase 3 gene (OR = 3.8634, 95% CI: 1.8285-8.1626, P = 0.004) and brain and acute leukemia, cytoplasmic (OR = 3.1538, 95% CI: 2.0537-4.8432, P< 0.0001) were associated with the ERG expression. In addition, the results showed a statistical significance between French-American-British (FAB) classification subtype (minimally differentiated AML and AML without maturation, OR = 4.7902, 95% CI: 2.7772-8.2624, P< 0.0001; acute monocytic leukemia, OR = 0.2324, 95% CI: 0.0899-0.6006, P = 0.0026) and ERG expression. CONCLUSION: High ERG expression might be used as a strong adverse prognostic factor in CN-AML.
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Biomarcadores de Tumor/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Perfilación de la Expresión Génica , Humanos , Pronóstico , Regulador Transcripcional ERG/metabolismoRESUMEN
PURPOSE: To investigate the variability and prognostic value of nodal tumor volume (NTV) in nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Data on 1230 patients with newly diagnosed stage T1-4N1-3M0 NPC treated with definitive radiation therapy with or without chemotherapy at a single cancer center were reviewed. NTV was determined from dose volume histogram (DVH) data. X-tile analysis was applied to identify the optimal cut-off points for the NTV with respect to regional recurrence-free survival (RRFS). Correlations between the TNM classification system, NTV and RRFS were assessed using a Cox regression model. Cross-validation based on receiver operating characteristic (ROC) curve analysis was applied to compare the prognostic predictive validity of NTV and N categories. RESULTS: Within a median follow-up of 49.9 (range, 1.27-76.40) months, 61/1230 (5%) patients developed regional recurrence and 154 (12.5%) developed distant metastasis. NTV values of 7.2 cc and 35.7 cc were identified as the optimal cut-off points. Patients with larger NTV had poorer prognosis. Compared with the N category, NTV was better at determining RRFS for patients with NPC. Hazard ratios increased with NTV, ranging from 1.86 (95% confidence interval [95% CI], 0.92-3.78) for NTV between 7.2 cc to 35.7 cc, and 3.67 (95% CI, 1.58-8.50) for NTV > 35.7 cc. With both NTV and N category in the same Cox regression model, only NTV remained statistically significant in the RRFS of NPC. The validation results with ROC curves also revealed that, NTV was superior to N category for predicting RRFS with significantly larger area under the ROC curve. CONCLUSIONS: NTV offers important prognostic value for treatment outcomes in NPC, especially regional control. Volumetric analysis of nodal involvement may assist selection of patients with poor prognosis.
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Carcinoma/patología , Metástasis Linfática/patología , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia/patología , Adolescente , Adulto , Anciano , Carcinoma/diagnóstico , Carcinoma/tratamiento farmacológico , Carcinoma/radioterapia , Femenino , Humanos , Metástasis Linfática/diagnóstico , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Nasofaringe/patología , Cuello/patología , Recurrencia Local de Neoplasia/diagnóstico , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Resultado del Tratamiento , Carga Tumoral , Adulto JovenRESUMEN
This study is to investigate the dose distribution of organs at risk (OARs) in cases of nasopharyngeal carcinoma (NPC). From July 2013 to October 2014, a prospective cohort study involving 148 patients was carried out at our center. OARs surrounding the nasopharynx were contoured on axial CT planning images in all patients. Dose-volume histograms of OARs and gross tumor volumes (GTV) were calculated. Multivariate analysis showed that radiation dose to OARs was associated with T stage and, especially, GTV. Seven OARs, including the spinal cord, eye and mandible, easily tolerated radiation doses in all patients; six OARs including the brain stem, chiasm and temporal lobe easily tolerated radiation doses in patients with a small GTV, but with difficulty when GTV was large; and other nine OARs including the parotid gland, cochlea and tympanic cavity met tolerance doses with difficulty in all patients. According to the patterns of radiation doses to OARs, it may help us to further reduce subsequent complications by improving the efficiency of plan optimization and evaluation.
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Neoplasias Nasofaríngeas/radioterapia , Órganos en Riesgo/efectos de la radiación , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Adulto , Anciano , Tronco Encefálico/efectos de la radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Nasofaríngeas/patología , Glándula Parótida/efectos de la radiación , Estudios Prospectivos , Médula Espinal/efectos de la radiación , Carga Tumoral/efectos de la radiaciónRESUMEN
Variations of PM2.5 concentrations and effects of pollution control measures during two red alert periods in 2015 in Beijing were analyzed based on atmospheric pollutant monitoring data. The results showed that during the first red alert, the highest hourly-averaged PM2.5 concentration occurred at 19:00 on 9th December with a value of 282 µg·m-3 and the highest hourly PM2.5 concentration appeared at Yongledian station which is near the southeast border of Beijing, with the peak concentration of 496 µg·m-3. During the second red alert, the highest hourly-averaged concentration of PM2.5 occurred at 20:00 on 22th with a value of 421 µg·m-3. The highest hourly PM2.5 concentration was monitored at Liulihe station which is near the southwest border of Beijing, with the peak concentration of 831 µg·m-3. During the duration period of both red alerts, the concentrations at the southern stations were higher than those at downtown stations and the PM2.5 concentrations at northern stations were found to be the smallest. The difference between these two red alerts was that during the second red alert, the PM2.5 concentrations in southern Beijing were significantly higher than those in the northern area, while the magnitude of this south-to-north gradient was much smaller during the first one. During the second red alert, up to 93% of Beijing area showed an average PM2.5 concentration of above 150 µg·m-3, which was much larger than that in the first one. The meteorological conditions during the two red alerts were both not conducive to the spread of pollutants. Formation of secondary pollutants and regional pollutant transport existed as well. Though the stagnant weather conditions were in favor of the development of severe pollution, large regional-wide pollutant emission was the main reason for these two heavy air pollutions in Beijing. PM2.5 concentrations were decreased by 20%-25% after the implementation of emergency response measures, which showed the significance of emission reduction in air pollution control.
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This study aimed to identify the dosimetric parameters and radiation dose tolerances associated with moderate or severe sternocleidomastoid muscle (SCM) atrophy after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). We retrospectively analysed 138 patients treated with IMRT between 2011 and 2012 for whom IMRT treatment plans and pretreatment and 3-year post-IMRT MRI scans were available. The association between mean dose (Dmean), maximum dose (Dmax), VX (% SCM volume that received more than X Gy), DX (dose to X% of the SCM volume) at X values of 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80 and SCM atrophy at 3 years after IMRT were analyzed. All dosimetric parameters, except V40, V50 and V80, were significantly associated with moderate or severe SCM atrophy. Multivariate analysis showed that V65 was an independent predictor of moderate or severe SCM atrophy (P < 0.001). Receiver operating characteristic (ROC) curve indicated a V65 of 21.47% (area under ROC curves, 0.732; P < 0.001) was the tolerated dose for moderate or severe SCM atrophy. We suggest a limit of 21.47% for V65 to optimize NPC treatment planning, whilst minimizing the risk of moderate or severe SCM atrophy.
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Atrofia Muscular/etiología , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidad Modulada/efectos adversos , Adolescente , Adulto , Anciano , Área Bajo la Curva , Carcinoma , Femenino , Humanos , Incidencia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Atrofia Muscular/epidemiología , Atrofia Muscular/patología , Carcinoma Nasofaríngeo , Curva ROC , Tolerancia a Radiación , Radiometría , Dosificación Radioterapéutica , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
The growth and physiology of bloom-forming cyanobacterium Microcystis aeruginosa were determined by the pulse amplitude modulated fluorimetry when exposed to different concentrations of Litchi chinensis defoliation extract for 15 d. The growth, maximal efficiency (Fv/Fm), effective quantum yield (YII) of PSII photochemistry, photosynthesis efficiency (α) , maximum electron transport rate (rETRmax) and light saturation coefficient (Ik) were used to evaluate the growth and photosynthesis in M. aeruginosa. It was found that the extract of L. chinensis defoliation stored for 5 days significantly inhibited the growth of M. aeruginosa in a concentration-dependent way. After a long time of exposure, stimulation effect disappeared gradually. Fv/Fm fluorescence parameters, YII and alpha changed from negative correlation to positive correlation or kept positive correlation with the extract of L. chinensis defoliation, which might affect the photosynthesis of M. aeruginosa at early time or help the cyanobacterium to survive in the stress environment by improving the efficiency of light energy. Ik, rETRmax and the content of algal chlorophyll-a changed from negative to significant negative correlation with the extract. Three-dimensional fluorescence spectra showed that the peak intensities of tryptophan and tyrosine fluorescence were only about one third in 2.0 g · L(-1) extract treatment when compared to the 1.2 g · L(-1) extract treatment on day 15. At the same time, the peak intensity of humic acid fluorescence was weaker than that on day 1. Further study showed that the EC50 of algal growth was smaller than that of the traditional crops straw, which might achieve good effect to control the growth of algae with lower concentration of L. chinensis defoliation extract due to its strong allelopathy.
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Litchi/química , Microcystis/efectos de los fármacos , Microcystis/fisiología , Fotosíntesis , Extractos Vegetales/química , Clorofila , Clorofila A , Transporte de Electrón , Fluorescencia , LuzRESUMEN
Relationship between high lung cancer incidence in Xuanwei residents and environmental pollution has been a hot topic in the field of environmental sciences. Street dusts in Xuanwei power plant area as well as its upwind area (Banqiao town) and downwind area (Laibin town, Tangtang town) were collected. Chemical elements in the street dust samples were investigated using ICP-MS. Health risk assessment of heavy metals in the street dusts was carried out using the US EPA Health Risk Assessment Model. Our results showed that the mass level of Al, V, Ni, Co, Zn and Cd in street dusts followed the order of Xuanwei power plant > Laibin town > Tangtang town. The mean concentrations of V, Cd, Cr, Cu, Mn, Co, Ni, Pb, As and Zn were all higher than the background values in Yunnan soil, indicating that the street dusts of Xuanwei city have been heavily polluted by those metals. The health risk assessment results showed that the non-cancer hazard risks induced by the 10 heavy metals were higher to children compared to adults. The heavy metals in street dust were mainly ingested by human bodies through hand-mouth ingestion. The 5 carcinogenic metals, including Cd, Cr, Ni, Cr and As, had a potential risk of carcinogenicity in human after exposed to the dusts. Cr was the major toxic element to the local children's health.
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Polvo/análisis , Monitoreo del Ambiente , Contaminación Ambiental/análisis , Metales Pesados/análisis , Adulto , Niño , China , Ciudades , Humanos , Modelos Teóricos , Centrales Eléctricas , Medición de Riesgo , Suelo/químicaRESUMEN
This paper reports a room temperature visible-light-driven protocol for the intermolecular [2+2] cycloadditions between coumarin-3-carboxylates and acrylamides analogs by an energy-transfer process. Using an iridium complex FIrPic as a photosensitizer and a 3â W blue LED as a light source, an array of cyclobutabenzocypyranones were prepared in moderate to excellent yields.
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Doxorubicin plays a major role in the treatment of osteosarcoma disorders. The Notch signaling pathway exerts various biological functions, including cell proliferation, differentiation, and apoptosis. In the present study, we investigated the effects of different doses of doxorubicin on proliferation and apoptosis of osteosarcoma cells with or without Notch signaling. Results found that cellular viability was downregulated while caspase 3 activity and expression were promoted in osteosarcoma cells following treatment with various doses of doxorubicin for 24, 48, and 72 h, and the effects showed a dose- and time-dependent manner. Furthermore, it was found that various doses of doxorubicin activated the Notch signaling pathway, shown by the elevated expression of Notch target genes NOTCH1, HEY1, HES1, AND HES5. It was further proved that, after small interfering RNA (siRNA)-mediated knockdown of Notch, the effects of doxorubicin on the viability and apoptosis of osteosarcoma cells were significantly reduced. It was indicated that doxorubicin treatment reduced the proliferation and promoted the apoptosis of osteosarcoma cells, and this effect was mediated by the Notch signaling pathway.
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Antibióticos Antineoplásicos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Doxorrubicina/farmacología , Osteosarcoma/tratamiento farmacológico , Receptores Notch/metabolismo , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Osteosarcoma/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , Interferencia de ARN , Receptor Notch1/genética , Receptor Notch1/metabolismo , Receptores Notch/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factores de Tiempo , Factor de Transcripción HES-1 , Transfección , Regulación hacia ArribaRESUMEN
OBJECTIVE: To establish and characterize imatinib-resistant gastrointestinal stromal tumor (GIST) xenografts. Further provided an ideal experimental platform through the imatinib-resistant GIST xenografts to investigate the mechanism of resistance to imatinib. METHODS: Imatinib-resistant GIST cells were injected under the skin of athymic nude mice to establish animal models of human imatinib-resistant GIST. The molecular and histopathologic features of GIST xenografts were also analysed and compared with their counterpart of cell lines. RESULTS: The xenograft tumor models had been established by subcutaneously injection of GIST cells into nude mice. Immunohistochemistry results showed CD117 expression was positive in GIST-PR2 xenograft tumor, but negative in GIST-R. In GIST-PR1, tumor areas showing rhabdomyoblastic differentiation were presented next to areas with classic GIST morphology. The rhabdomyoblastic component demonstrated consistently positivity for desmin and myogenin, whereas CD117 was completely negative. The mutation profiles of these xenograft tumors were the same as their counterpart of cell lines. CONCLUSIONS: Human GIST xenografts with mutation in c-kit have been established from imatinib-resistant GIST lines. Those models will enable further studies on mechanisms of resistance, combination therapies and allow testing of novel targeted therapies.
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Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/patología , Proteínas Proto-Oncogénicas c-kit/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Antineoplásicos/farmacología , Benzamidas , Diferenciación Celular , Línea Celular Tumoral , Desmina/metabolismo , Resistencia a Antineoplásicos , Femenino , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/metabolismo , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/metabolismo , Humanos , Mesilato de Imatinib , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Mutación , Miogenina/metabolismo , Piperazinas/farmacología , Proteínas Proto-Oncogénicas c-kit/genética , Pirimidinas/farmacología , Rabdomiosarcoma/metabolismo , Rabdomiosarcoma/patologíaRESUMEN
Ambient particulate matters (PM) and allergenic pollens in urban atmosphere have taken negative effects on human health and air quality. Studies on synergistic effects between the two pollutants are being focused in disciplines, such as atmospheric sciences, environmental toxicology, and immunology. In this study, physicochemical characterization of airborne fine/ultrafine particles in Shanghai, China and ambient allergenic pollens (cedar) in Kanto, Japan were investigated. We found that allergenic protein particles (Ubisch body) with diameter less than 0.7 microm were absorbed on Japanese cedar pollen, and airborne particles which contained allergenic particles mainly distributed in < 1 microm size range. The highest mass concentration of chemical elements in Shanghai airborne particles was found in the 0.3-0.18 microm size range, but mass level of pollutant elements, such as S and Pb, in ambient in ultrafine (nano) particles were higher than that in coarse and fine particles. And also, pollen particles were found in Shanghai airborne particles. Synergistic effects between diesel exhaust particles (DEPs), which were the main component in urban airborne particles, and ambient pollens in urban atmosphere can be found, but their mechanism have not been clear. After our new results and other conclusions published recently on allergenic pollen and airborne fine/ultrafine particles were summarized, perspectives of this new discipline were presented.