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Sludge retention time (SRT) regulation is one of the essential management techniques for refined control of the main-sidestream treatment process under the low ammonia density. It is indispensable to understand the effect of SRTs changes on the Nitrifier kinetics to obtain the functional separation of the Nitrifier and the refined control of the nitrification process. In this study, Nitrifier was cultured with conditions of 35 ± 0.5 °C, pH 7.5 ± 0.2, DO 5.0 ± 0.5 mg-O/L, and SRTs were controlled for 40 d, 20 d, 10 d, and 5 d. The net growth rate (µm), decay rate (b), specific growth rate (µ), the yield of the Nitrifier (YA), temperature parameter (TA), and inhibition coefficient (KI) have been measured and extended with the SRT decreases. Instead, the half-saturation coefficient (KS) decreased. In addition, the limited value of pH inhibition occurs (pHUL), and the pH of keeping 5% maximum reaction rate (pHLL) was in a relatively stable state. The trade of kinetics may be induced by the change of species structure of Nitrifier. The Nitrosomonas proportion was increased, and the Nitrospira was contrary with the SRT decreasing. It is a match for the functional separation of Nitrifier when SRTs was 20 d at ambient temperature under the low ammonia density. The kinetics of ammonia-oxidizing organisms (AOO) and nitrite-oxidizing organisms (NOO) in Nitrifier under different SRT conditions should be measured respectively to the refined control of the partial nitrification process in future study.
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Amônia , Esgotos , Reatores Biológicos , Cinética , TemperaturaRESUMO
The objective of this study is to explore the optimal pre-treatment procedures and statistics methods for live/dead bacterial staining using nitrite oxidizing organism (NOO) as the research aim. This staining method was developed and widely utilized to evaluate activated bacterial survival situation, because it is direct and convenience to count live and dead bacteria amount by colour distinguishes (green/red) from pictures taken by microscope. The living cell (green colour) percentage and initial bacterial chemical oxygen demand (COD) could be used for accurate reaction rate calculation at the beginning of tests. While according to the physiological principles, the detection target was limited as the organism has a complete cell shape, that was applicable for the initial phase for decay stage (live cell â particulate dead cell), but it is impossible to evaluate the decayed soluble COD from particulate dead cell during whole reaction. To model the decay stage scientifically, a two-step decay model was developed to cater to the live/dead bacterial staining analysis of biological nitrite oxidizer under inhibition condition of high nitrite concentrations at 35 °C. As results of optimal pre-treatment, a three level ultrasonic wave with 45 seconds was explored, as a reasonable observed picture number, 30 sets with 95% confident interval for datasets statistics was summarized. A set of nitrite oxidizer inhibition test (total COD and oxygen uptake rates) under high nitrite concentrations was simulated using the above model and obtained experimental schemes. Additionally, the disintegration enhancement from particulate dead cell to soluble COD by nitrite was inspected and modelled on the basis of experimental datasets.
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Nitritos , Esgotos , Bactérias , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos , OxirreduçãoRESUMO
Nitrogen and silicon co-doped carbon nanodots (N/Si-CDs) were synthesized by one-step hydrothermal carbonization of folic acid and 3-aminopropyl trimethoxy silane with the assistance of glycerol. The resultant N/Si-CDs present intense excitation-independent photoluminescence (PL) emission owing to their monodisperse sizes and specific surface states. In comparison to nitrogen single doped CDs (N-CDs), the co-doped N/Si-CDs possess better PL properties following different emission manner due to the synergistic effects of the nitrogen and silicon dopants. Besides, the functionalized surfaces of N/Si-CDs endow them with superior solubility and stability. The as-synthesized N/Si-CDs demonstrate selective and sensitive fluorescence response to Fe3+, which could be explained by the PL quenching effects of Fe3+ on N/Si-CDs. Based on this finding, the quantitative analysis of aqueous Fe3+ by N/Si-CDs was established, showing good linearity in a range of 10 nM~45 µM and good sensitivity with a detection limit of 3.8 nM, so did for the detection of Fe3+ in fetal bovine serum (FBS) spiked samples. Therefore, the N/Si-CDs as a novel fluorescence probe hold promising for monitoring environmental and clinical Fe3+.
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Alpha-lipoic acid (ALA) is a naturally occurring compound synthesized by mitochondria and widely distributed in both animal and plant tissues. It primarily influences cellular metabolism and oxidative stress networks through its antioxidant properties and is an important drug for treating metabolic diseases associated with oxidative damage. Nevertheless, research indicates that the mechanism by which ALA affects cancer cells is distinct from that observed in normal cells, exhibiting pro-oxidative properties. Therefore, this review aims to describe the main chemical and biological functions of ALA in the cancer environment, including its mechanisms and effects in tumor prevention and anticancer activity, as well as its role as an adjunctive drug in cancer therapy. We specifically focus on the interactions between ALA and various carcinogenic and anti-carcinogenic pathways and discuss ALA's pro-oxidative capabilities in the unique redox environment of cancer cells. Additionally, we elaborate on ALA's roles in nanomedicine, hypoxia-inducible factors, and cancer stem cell research, proposing hypotheses and potential explanations for currently unresolved issues.
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Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors (PEComas) because PEComas are mainly benign tumors and may not require surgical intervention. By analyzing the causes, properties and clinical manifestations of PEComas, we summarize the challenges and solutions in the diagnosis of PEComas.
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Neoplasias Hepáticas , Neoplasias de Células Epitelioides Perivasculares , Humanos , Neoplasias de Células Epitelioides Perivasculares/cirurgia , Neoplasias de Células Epitelioides Perivasculares/patologia , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico , Hepatectomia , Cuidados Pré-Operatórios/métodos , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Fígado/patologia , Fígado/cirurgia , Fígado/diagnóstico por imagemRESUMO
Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare subtype of follicular dendritic cell sarcoma (FDCS) that primarily occurs in the liver and spleen. The etiology of IPT-like FDCS is unknown, and it has nonspecific clinical manifestations, imaging performance and laboratory test results. Recently, a patient with IPT-like FDCS was admitted to our hospital because of abdominal distension and anemia. Over the past 3 years, the patient has been followed up after a liver mass was found in a physical examination. The lesion gradually enlarged and caused compression symptoms. In November 2022, a tumor with a diameter of approximately 20 cm was found in the right posterior lobe of the liver after abdominal enhanced Magnetic resonance imaging (MRI) in our hospital. Liver tumor biopsy before the operation revealed a large number of hyperplastic plasma cells and a small number of spindle cells, and the spindle cells were atypical. After a complete examination, the patient underwent liver resection. Pathology after surgery confirmed liver IPT-like FDCS.
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BACKGROUND: Liver cancer resection, especially in patients with hemihepatectomy or extended hemihepatectomy, often leads to poor prognosis, such as liver insufficiency and even liver failure and death, because the standard residual liver volume (SRLV) cannot be fully compensated after surgery. AIM: To explore the risk factors of poor prognosis after hemihepatectomy for hepatocellular carcinoma and evaluate the application value of related prognostic approaches. METHODS: The clinical data of 35 patients with primary liver cancer in Nantong Third People's Hospital from February 2016 to July 2020 were retrospectively analyzed. The receiver operating characteristic curve was created using medcac19.0.4 to compare the critical values of the SRLV in different stages of liver fibrosis after hemihepatectomy with those of liver dysfunction after hemihepatectomy. It was constructed by combining the Child-Pugh score to evaluate its application value in predicting liver function compensation. RESULTS: The liver stiffness measure (LSM) value and SRLV were associated with liver dysfunction after hemihepatectomy. Logistic regression analysis showed that an LSM value ≥ 25 kPa [odds ratio (OR) = 6.254, P < 0.05] and SRLV ≤ 0.290 L/m2 (OR = 5.686, P < 0.05) were independent risk factors for postoperative liver dysfunction. The accuracy of the new liver reserve evaluation model for predicting postoperative liver function was higher than that of the Child-Pugh score (P < 0.05). CONCLUSION: SRLV and LSM values can be used to evaluate the safety of hemihepatectomy. The new liver reserve evaluation model has good application potential in the evaluation of liver reserve function after hemihepatectomy.
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The precipitation of struvite (MgNH4PO4·6H2O) is considered to be a promising method for the recovery of phosphate from wastewater. In this review, the kinetic models, which are commonly used to explain the process of struvite crystallization, are described. The mixed-suspension mixed-product removal (MSMPR) model is based on the population balance equation (the size-dependent growth model and the size-independent growth model). Thereafter, the first-order kinetic fitting model that aligned with concentration changes in the substrate is summarized. Finally, the several physical and chemical factors that affected the efficiency of struvite crystallization are determined. The supersaturation ratio, which is seen as the driving force of struvite crystallization, is the main factor that influences crystallization; however, it cannot be used in practical applications of engineering because it is indirectly associated with the following factors: pH, the molar ratio of Mg:N:P, and the interference of foreign impurities. In this study, we present conclusions that should be used to guide further research studies, and encourage the engineering practice of wastewater treatment with struvite precipitation.
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Fosfatos , Águas Residuárias , Precipitação Química , Cristalização , Cinética , Fosfatos/química , Fósforo/química , Estruvita/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/químicaRESUMO
Realgar (As4S4) has been used in traditional Chinese medicines for treatment of malignancies. The poor solubility of As4S4 hampered its clinical applications. Realgar quantum dots (RQDs) were developed to overcome these problems. Previous studies revealed that the RQDs were effective against endometrial cancer JEC cells and hepatocarcinoma HepG2 cells via inducing apoptosis.Apoptosis and autophagy are important programmed cell death pathways leading to anticancer effects. This study further examined effects of RQDs on autophagy, focusing on the formation of the autophagosome in JEC cells. CCK8 assay was used to examine cell proliferation. Flow cytometry was used to analyze cell cycle. Transmission electron microscopy (TEM) was used to examine the autophagy, cells were transfected with pEGFP-C3-MAP1LC3B plasmid to examine effects of RQDs on autophagosome via confocal microscope. Autophagy-related proteins were examined by Western blot. RQDs exhibited cytotoxicity in JEC cells in a concentration- and time- dependent manner. RQDs induced G2 and S phase arrest in JEC cells. RQDs significantly induced autophagy, with the double-membrane and autophagosome-like structures by TEM. The diffused distribution of pEGFP-C3-MAP1LC3B green fluorescence were become the punctuate pattern fluorescence after treatment with RQDs in cells transfected with pEGFP-C3-MAP1LC3B plasmid RQDs increased the expression of autophagyregulatory proteins LC3 I/II, Beclin-1, p62 and Atg12 in a concentration-dependent manner, similar to autophagy induced by serum starvation, except for p62, as induction of p62 is a characteristic of arsenic compounds. Taken together, the present study clearly demonstrated that RQDs can induce autophagy in JEC cells as one of mechanisms of anticancer effects, and indicated that RQDs may be developed as an autophagy inducer.
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PURPOSE: To investigate the association between various arsenicals and the potential oxidative stress caused, we examined the urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dGuo), a biomarker of oxidative DNA damage in rats after daily oral administration of arsenic trioxide/arsenite (As(2)O(3)), realgar (alpha-As(4)S(4)) and orpiment (As(2)S(3)) over 14 days and compared the levels with control rats. METHODS: 8-OH-dGuo in urine was quantified with isotope-dilution liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) after sample cleaning with solid phase extraction (SPE). Urinary arsenic concentrations were measured by graphite furnace atomic absorption spectrometry (GFAAS). RESULTS: All arsenicals caused elevated urinary 8-OH-dGuo excretion in rats from day 1 after oral administration (p < 0.01 respectively). There were significant correlations between urinary 8-OH-dGuo and urinary arsenic levels (slope = 0.8164, 0.5801, 0.6582; r (2) = 0.5946, 0.7883, 0.8426 for arsenite, realgar and orpiment-treated group respectively, p < 0.001). This illustrates that urinary 8-OH-dGuo level could be a valid biomarker for detecting the extent of arsenic exposure. Arsenite was found to cause significantly higher urinary 8-OH-dGuo levels than both realgar and orpiment (p < 0.01) even after creatinine and dose adjustments. CONCLUSIONS: Arsenite could cause more oxidative DNA damage than both realgar and orpiment and may be more genotoxic.
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Arsenicais/efeitos adversos , Cromatografia Líquida/métodos , Dano ao DNA/efeitos dos fármacos , Desoxiguanosina/análogos & derivados , Espectrometria de Massas em Tandem/métodos , 8-Hidroxi-2'-Desoxiguanosina , Animais , Arsenicais/administração & dosagem , Arsenitos/administração & dosagem , Arsenitos/efeitos adversos , Desoxiguanosina/urina , Oxirredução , Ratos , Ratos Sprague-Dawley , Sulfetos/administração & dosagem , Sulfetos/efeitos adversosRESUMO
Desoxyrhapontigenin (DRG, 4-methoxyresveratrol or trans-3,5-dihydroxy-4'-methoxystilbene) is a naturally occurring resveratrol (RES) derivative with a variety of biological activities. To facilitate its further medicinal exploration, a reliable LC-MS/MS method was developed and validated for the quantification of DRG in rat plasma using heavy isotope labelled RES as an internal standard. The ESI was operated in its negative ion mode while DRG and RES were determined by multiple reaction monitoring (MRM) using precursor-to-product ion transitions of m/z 241.1â¯ââ¯180.8 and m/z 233.0â¯ââ¯191.0, respectively. This LC-MS/MS method displayed excellent selectivity, sensitivity (LLOQâ¯=â¯2.5â¯ng/ml), accuracy (both intra- and interday mean analytical recovery within 100⯱â¯15%) and precision (both intra- and interday CVâ¯<â¯15%). The mean matrix factors were all within 1.000⯱â¯0.150 with CVâ¯<â¯15%. The pharmacokinetic profiles of DRG were subsequently examined in Sprague-Dawley rats. Upon intravenous administration (4 or 10â¯mg/kg), DRG displayed very rapid clearance (Clâ¯=â¯338⯱â¯66 or 275⯱â¯30â¯ml/min/kg) and short mean residence time (MRTâ¯=â¯12.9⯱â¯4.7 or 10.4⯱â¯0.5â¯min). After oral administration of DRG fully solubilized by 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), the plasma profiles of DRG were highly erratic with a low absolute bioavailability (Fâ¯<â¯9.83⯱â¯5.31%). When DRG was given at a higher dose (50â¯mg/kg) in suspension form, the F was increased to 24.1⯱â¯5.6%. The pharmacokinetic comparison among DRG, RES and some of its hydroxyl analogues stilbenes was performed. The information obtained from this study will facilitate further exploration on DRG as well as other RES derivatives.
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Plasma/química , Estilbenos/sangue , Estilbenos/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Cromatografia Líquida/métodos , Infusões Intravenosas/métodos , Masculino , Ratos , Ratos Sprague-Dawley , Resveratrol , Espectrometria de Massas em Tandem/métodosRESUMO
Bismuth dithiocarbamate complexes of general formula Bi(S(2)CNR(2))(3) demonstrate potent in vitro cytotoxicity against a panel of seven human cancer cell lines; a structure-activity relationship has been established. Potency exhibited by the R=Et (2) derivative, for example, is unrivalled by standard cancer drugs with the exception of paclitaxel. In vivo studies indicate a significant anti-tumor effect exerted by (2) against both OVCAR-3, an ovarian cancer cell line, and HT-29, a colon carcinoma cell line.
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Bismuto/farmacologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Tiocarbamatos/química , Tiocarbamatos/farmacologia , Animais , Bismuto/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Feminino , Células HT29 , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Compostos Organometálicos/síntese química , Neoplasias Ovarianas/tratamento farmacológico , Relação Quantitativa Estrutura-Atividade , Distribuição Aleatória , Espectrofotometria Infravermelho , Tiocarbamatos/síntese química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
An environmentally friendly atomic layer deposition (ALD) method with excellent atomic scale roughness controllability is developed to fabricate a highly conformal, corrosion preventive and conducting Al doped ZnO (AZO) film on a plasma electrolytic oxidation (PEO) layer coated AZ31 magnesium alloy. Compared with the insulated PEO coated magnesium alloy, the electrical conductivity of the composite coating increases to 25 S m-1, and in the meantime the anticorrosion performance of the PEO/AZO coating is greatly improved compared to the bare Mg alloy. The enhanced electrical properties of the composite coating are due to the abundant oxygen deficiency in the AZO film generated during the ALD process. The improvement of the corrosion resistance is attributed to the changes in the bond angle and the distance between the surface coating molecule and adsorbent H2O molecule. As a result, the hydrophilic surface of PEO changes to the hydrophobic surface of AZO, providing a novel process to protect the surface of the magnesium alloy. It is believed that this technique may provide a novel and controllable strategy to expand the practical applications of magnesium alloys.
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Highly conductive and optical transparent Al-doped ZnO (AZO) thin film composed of ZnO with a Zn-Al-O interface was fabricated by thermal atomic layer deposition (ALD) method. The as-prepared AZO thin film exhibits excellent electrical and optical properties with high stability and compatibility with temperature-sensitive flexible photoelectronic devices; film resistivity is as low as 5.7 × 10-4 Ω·cm, the carrier concentration is high up to 2.2 × 1021 cm-3. optical transparency is greater than 80% in a visible range, and the growth temperature is below 150 °C on the PEN substrate. Compared with the conventional AZO film containing by a ZnO-Al2O3 interface, we propose that the underlying mechanism of the enhanced electrical conductivity for the current AZO thin film is attributed to the oxygen vacancies deficiency derived from the free competitive growth mode of Zn-O and Al-O bonds in the Zn-Al-O interface. The flexible transparent transistor based on this AZO electrode exhibits a favorable threshold voltage and Ion/Ioff ratio, showing promising for use in high-resolution, fully transparent, and flexible display applications.
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Arsenic trioxide (As2O3) has been a research focus because of its promising anticancer effects especially in the treatment of leukemia. Another arsenic compound, realgar (As2S2), has long been used as a therapeutic agent to treat some diseases in ancient China and Europe, and its medicinal effects have attracted increasing attentions in recent years. However, its poor water-solubility unfortunately results in poor bioavailability and hampers it from being studied and used for possible clinical application. In this study, nanosized realgar particles were prepared by cryo-grinding with polyvinylpyrrolidone (PVP) and/or sodium dodecyl sulfate (SDS). Major physical properties of the respective nanosized realgar particles were characterized. Co-grinding realgar with PVP and/or SDS produced smaller and more monodisperse suspension of nanoparticles. The in vitro cytotoxic effects of such nanosized realgar particles on selected human ovarian (CI80-13S, OVCAR, OVCAR-3) and cervical (HeLa) cancer cell lines were investigated. Significant anti-proliferation effect of these realgar nanoparticles on these cancer cell lines was observed. CI80-13S was most sensitive to the nanosized realgar particles with IC50 values of less than 1 microM as As2S2, whereas the other cancer cell lines had IC50 values in a range of 2-4 microM as As2S2. The cytotoxic activity of the realgar nanoparticles to these human gynecological cell lines was comparable to arsenic trioxide observed previously. In these cancer cell lines, the cytotoxic effects were caused by apoptosis as confirmed by cell cycle and DNA laddering analysis. In in vivo study, a remarkable increase in urinary recovery of arsenic was observed in rats after a single oral administration of the cryo-ground realgar particle suspension. Ranging from 58.5 to 69.6% of the administered dose of arsenic was recovered in urine in the first 48 h from the PVP and/or SDS co-ground preparations; whereas the original realgar powder gave a urinary recovery of only 24.9%. The finding suggested that size reduction of realgar particles to nano levels could enhance its bioavailability substantially.
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Antineoplásicos/farmacocinética , Arsenicais/farmacocinética , Sulfetos/farmacocinética , Animais , Antineoplásicos/administração & dosagem , Arsenicais/administração & dosagem , Disponibilidade Biológica , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Creatinina/urina , Cristalografia por Raios X , Fragmentação do DNA , Composição de Medicamentos , Excipientes , Fibroblastos , Citometria de Fluxo , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Nanoestruturas , Tamanho da Partícula , Povidona , Ratos , Ratos Sprague-Dawley , Dodecilsulfato de Sódio , Espectrofotometria Atômica , Sulfetos/administração & dosagemRESUMO
In this communication, we present a versatile and controllable strategy for formation of superhydrophobic micro/nano hierarchical Al doped ZnO (AZO) films with a water contact angle (CA) of 170 ± 4°. This strategy involves a two-step layer-by-layer process employing an atomic layer deposition (ALD) technique followed by a hydrothermal method, and the resulting novel AZO surface layer consists of (100) dominant nano-rice-like AZO seed layer (the water CA of 110 ± 4°) covered with micro-peony-like AZO top. The growth mechanisms and superhydrophobic properties of the hierarchical AZO layer are discussed. It is believed that the present route holds promise for future success in the design and development of practical superhydrophobic materials.
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Realgar (AS4S4) has been used in traditional medicines for malignancy, but the poor water solubility is still a major hindrance to its clinical use. Realgar quantum dots (RQDs) were therefore synthesized with improved water solubility and bioavailability. Human endometrial cancer JEC cells were exposed to various concentrations of RQDs to evaluate their anticancer effects and to explore mechanisms by the MTT assay, transmission electron microscopy (TEM), flow cytometry, real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. Results revealed that the highest photoluminescence quantum yield of the prepared RQDs was up to approximately 70%, with the average size of 5.48 nm. RQDs induced antipro-liferative activity against JEC cells in a concentration-dependent manner. In light microscopy and TEM examinations, RQDs induced vacuolization and endoplasmic reticulum (ER) dilation in JEC cells in a concentration-dependent manner. ER stress by RQDs were further confirmed by increased expression of GADD153 and GRP78 at both mRNA and protein levels. ER stress further led to JEC cell apoptosis and necrosis, as evidenced by flow cytometry and mitochondrial membrane potential detection. Our findings demonstrated that the newly synthesized RQDs were effective against human endometrial cancer cells. The underlying mechanism appears to be, at least partly, due to ER stress leading to apoptotic cell death and necrosis.
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Apoptose/efeitos dos fármacos , Neoplasias do Endométrio/genética , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Necrose/patologia , Pontos Quânticos/toxicidade , Sulfetos/toxicidade , Arsenicais , Linhagem Celular Tumoral/efeitos dos fármacos , Neoplasias do Endométrio/patologia , Chaperona BiP do Retículo Endoplasmático , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Potencial da Membrana Mitocondrial , Microscopia Eletrônica de Transmissão , Necrose/induzido quimicamente , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismoRESUMO
Realgar (As4S4) has been used in traditional Chinese medicines for treatment of malignancies. However, the poor water solubility of realgar limits its clinical application. To overcome this problem, realgar quantum dots (RQDs; 5.48±1.09 nm) were prepared by a photoluminescence method. The mean particle size was characterized by high-resolution transmission electron microscopy and scanning electron microscopy. Our recent studies revealed that the RQDs were effective against tumor growth in tumor-bearing mice without producing apparent toxicity. The present study investigated their anticancer effects and mechanisms in human hepatocellular carcinoma (HepG2) cells. The HepG2 cells and human normal liver (L02) cells were used to determine the cytotoxicity of RQDs. The portion of apoptotic and dead cells were measured by flow cytometry with Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Apoptosis-related proteins and genes were examined by western blot analysis and reverse transcription-quantitative polymerase chain reaction, and the mitochondrial membrane potential was assayed by confocal microscope with JC-1 as a probe. RQDs exhibited cytotoxicity in a concentration-dependent manner and HepG2 cells were more sensitive compared with normal L02 cells. At 15 µg/ml, 20% of the cells were apoptotic, while 60% of the cells were necrotic at 30 µg/ml. The anti-apoptosis protein Bcl-2 was dose-dependently decreased, while pro-apoptotic protein Bax was increased. There was a loss of mitochondrial membrane potential and expression of the stress genes C/EBP-homologous protein 10 and glucose-regulated protein 78 was increased by RQDs. RQDs were effective in the inhibition of HepG2 cell proliferation and this effect was due to induction of apoptosis and necrosis through endoplasmic reticulum stress.
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A capillary zone electrophoresis (CZE) method with indirect UV detection was developed to simultaneously separate inorganic and organic arsenic compounds including arsenite (iAsIII), arsenate (iAsV), monomethylarsonate and dimethylarsenic acid (DMAV). 2,6-Pyridinedicarboxylic acid (PDC) and n-hexadecyltrimethylammonium hydroxide (CTAOH) were selected to compose a background electrolyte (BGE), where PDC was used as chromophore and CTAOH functioned as electroosmotic flow (EOF) modifier to reduce/eliminate EOF. The choice of detection wavelength, the optimization of BGE pH, and effects of applied electric field strength and temperature on separation were further investigated. The limits of detection for the targeted analytes were between 0.19 and 0.23 ppm as molecule. Good linearity of more than three orders of magnitude was obtained. Repeatability of migration times and peaks areas were 0.8-1.7 and 3.4-6.9% R.S.D.; whereas reproducibility were 1.2-2.2 and 3.6-7.1% R.S.D., respectively. The established CZE method was then applied to analyze the alkali extracts of realgar (As2S2) and orpiment (As2S3). The main components in both alkali extracts were identified to be iAsIII and iAsV.
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Arsenicais/análise , Arsenicais/química , Eletroforese Capilar/métodos , Álcalis/química , Arsenicais/isolamento & purificação , Calibragem , Compostos Inorgânicos/análise , Compostos Inorgânicos/química , Compostos Organometálicos/análise , Compostos Organometálicos/química , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta , Sulfetos/análise , Sulfetos/químicaRESUMO
Pinosylvin (trans-3,5-dihydroxystilbene), a naturally occurring analogue of resveratrol (trans-3,5,4'-trihydoxystilbene), exhibited various beneficial pharmacological activities in pre-clinical studies. To further probe its potential medicinal application, a sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed and validated for the quantification of pinosylvin in rat plasma. A simple protein precipitation procedure was used for plasma cleanup before analysis by LC-MS/MS with electrospray ionisation and multiple reaction monitoring in its negative ion mode. This LC-MS/MS method demonstrated good selectivity, accuracy (intra- and inter-day analytical recovery within 100±7.7%), precision (intra- and inter-day coefficient of variation<12.0%) and sensitivity (lower limit of detection=1.0ng/mL), with excellent linearity (R(2)>0.99) over the range of 1-1000ng/mL. The pharmacokinetic profiles of pinosylvin were subsequently assessed in Sprague-Dawley rats. Following intravenous administration (5 or 10mg/kg), plasma levels of pinosylvin declined rapidly with a short half-life (t1/2<10min). Upon oral administration at 15mg/kg, pinosylvin could not be quantified in plasma (<1ng/mL) while dose-escalation to 50mg/kg led to a low and erratic plasma exposure with very poor estimated oral bioavailability (F<1%). The short half-life and limited systemic exposure of pinosylvin prompt caution in its therapeutic application and it warrants exploration in developing pinosylvin pro-drug.