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In this study, a rapid screening method for elemental impurities in pharmaceutical products has been established by portable energy dispersive X-ray fluorescence (EDXRF) spectroscopy combined with the efficient fundamental parameter method. The proposed method has been used for the screening of 22 elemental impurities (i.e., Cd, Pb, As, Hg, Co, V, Ni, Tl, Au, Pd, Ir, Os, Rh, Ru, Se, Ag, Pt, Sb, Mo, Cu, Sn, and Cr) in the International Conference on Harmonization (ICH) Q3D guideline. The verification of results could meet the acceptance criteria for accuracy, precision and linearity in the United States Pharmacopoeia ã233ã. On the other hand, the limit of quantitation of the proposed EDXRF method for the screening of 22 elemental impurities in pharmaceutical products could meet the concentration limits of each element at 10 g maximum daily intake based on the established permitted daily exposure to oral drugs in the ICH Q3D guideline. Our findings open up new possibilities in the rapid screening of pharmaceutical products for the detection of elemental impurities by EDXRF, which can be expected to provide a novel, nondestructive, high-throughput, portable, and sensitive platform for the process control of elemental impurities to ensure the quality and safety of drugs.
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Contaminación de Medicamentos , Mercurio , Rayos X , Contaminación de Medicamentos/prevención & control , Radiografía , Preparaciones FarmacéuticasRESUMEN
OBJECTIVES: Because the purity of the two impurities reference standard (RS) of cefathiamidine is not easy to obtain, HPLC-PDA-ELSD were used to determin the RRFs of cefathiamidine impurities. METHODS: Peak area correction was applied to calculate RRFs to eliminate the influence of different responses caused by the difference in pH between the two mobile phases of HPLC-PDA and HPLC-PDA-ELSD. The resulting RRF values have been verified by qNMR. CONCLUSION: The new calcution method described in this article provides a reliable research idea for determintion the RRFs by HPLC-PDA-ELSD, especially when the purity of RS is unknown and the mobile phase of HPLC-PDA and HPLC-PDA-ELSD have difference. This method can be mutually verified with qNMR to ensure the accuracy of RRFs. It is also promingsing replace determination RRF by qNMR becausing economical, simple and low cost.
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Luz , Cromatografía Líquida de Alta Presión , Dispersión de RadiaciónRESUMEN
Chinese officials play an important role in air pollution control. This paper used a sample of 282 prefecture-level cities in China to discuss the impact of promotion incentives of officials on air pollution from the perspectives of heterogeneity, mechanism and spatial effects. We found that the promotion incentives of officials reduced air pollution, and GDP per capita had positive moderating effects. The effects of promotion incentives were more significant in cities with less air pollution, in the central and western regions, for officials with higher education levels, or years after 2007. The promotion incentives could promote the development of green finance and green technology innovation, both of which were conducive to mitigating air pollution. Using the dynamic spatial Durbin model (DSDM), we found that the promotion incentives had negative spatial spillover effects. The promotion incentives in surrounding cities reduced air pollution in the local city; however, it had only short-run effects and no long-run effects.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China , Ciudades , Conservación de los Recursos Naturales , MotivaciónRESUMEN
Antibiotics are widely used to treat bacterial infections during the process of vaccine production and storage resulting in antibiotic residues that can cause serious harm. A simple and sensitive method for residue analysis of 40 ß-lactam antibiotics was developed and validated for vaccines including inactivated enterovirus 71 vaccine (Vero cells), recombinant hepatitis B vaccine (Saccharomyces cerevisiae), and live attenuated varicella vaccine using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI- MS/MS). Samples were prepared with acetonitrile as the protein precipitant. LC separation was performed on a C18 column. These analytes were determined by LC-MS/MS operating multiple-reaction monitoring (MRM) scans in positive mode. The ranges for limits of detection (LOD) and quantification (LOQ) were as follows: 0.02-4 ng/dose (S/N ≥ 3) and 0.04-10 ng/dose in inactivated enterovirus 71 vaccine (Vero cells) and recombinant hepatitis B vaccine (Saccharomyces cerevisiae), 0.04-16 ng/dose and 0.2-20 ng/dose in live attenuated varicella vaccine. The ranges of recoveries of all antibiotics were 84.5%-108.2% in inactivated enterovirus 71 vaccine (Vero cells), 73%-108% in recombinant hepatitis B vaccine (Saccharomyces cerevisiae), and mostly 68.2%-107.8% in live attenuated varicella vaccine. This method simultaneously offers qualitative and quantitative analysis of multi-antibiotics in vaccines, which improves vaccine safety.
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Antibacterianos/análisis , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Vacunas/análisis , beta-Lactamas/análisis , Animales , Vacuna contra la Varicela/análisis , Chlorocebus aethiops , Contaminación de Medicamentos , Vacunas contra Hepatitis B/análisis , Límite de Detección , Reproducibilidad de los Resultados , Saccharomyces cerevisiae , Células VeroRESUMEN
In this study, a novel colorimetric aptasensor was developed for the rapid detection and visual screening of HPV16 L1 proteins using gold nanoparticles (AuNPs) and an RNA aptamer against HPV16 L1 protein (APTHPV16 L1). The AuNP-APTHPV16 L1 conjugates could be aggregated by the addition of a salt in the presence of HPV16 L1 proteins at the ppb level. At the same time, the surface plasma resonance absorption peaks of AuNPs shifted to a short wavelength, and an observable change in color from red to blue occurred. The relative absorbance (Ablank - Asample/Ablank) at 520 nm exhibited a stable response to HPV16 L1 proteins over a concentration range from 9.6 to 201.6 ng mL-1. The visual detection limit of HPV16 L1 proteins was found to be 9.6 ng mL-1. Finally, the proposed colorimetric aptasensor was successfully applied for the rapid and effective detection of HPV16 L1 proteins in clinical samples and vaccine samples. The validity and reliability of the proposed colorimetric aptasensor were verified by the enzyme-linked immunosorbent assay method. The proposed colorimetric aptasensor provided a promising indicator for screening and quantitative detection of HPV16 L1 proteins in clinical samples.
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Alphapapillomavirus , Aptámeros de Nucleótidos , Técnicas Biosensibles , Proteínas de la Cápside , Nanopartículas del Metal , Proteínas Oncogénicas Virales , Colorimetría , Oro , Papillomavirus Humano 16 , Humanos , Reproducibilidad de los ResultadosRESUMEN
Drug detection and identification technology are of great significance in drug supervision and management. To determine the exact source of drugs, it is often necessary to directly identify multiple varieties of drugs produced by multiple manufacturers. Near-infrared spectroscopy (NIR) combined with chemometrics is generally used in these cases. However, existing NIR classification modeling methods have great limitations in dealing with a large number of categories and spectra, especially under the premise of insufficient samples, unbalanced samples, and sensitive identification error cost. Therefore, this paper proposes a NIR multi-classification modeling method based on a modified Bidirectional Generative Adversarial Networks (Bi-GAN). It makes full utilization of the powerful feature extraction ability and good sample generation quality of Bi-GAN and uses the generated samples with obvious features, an equal number between classes, and a sufficient number within classes to replace the unbalanced and insufficient real samples in the courses of spectral classification. 1721 samples of four kinds of drugs produced by 29 manufacturers were used as experimental materials, and the results demonstrate that this method is superior to other comparative methods in drug NIR classification scenarios, and the optimal accuracy rate is even more than 99% under ideal conditions.
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Preparaciones Farmacéuticas , Espectroscopía Infrarroja CortaRESUMEN
A new water-soluble 4-amino-1, 8-naphthalimide based fluorescent sensor, with iminoacetic acid and iminoethoxyacetic acid as receptor contained two different arms, was developed. Under physiological pH conditions, it demonstrates good water solubility, high selectivity and sensitivity for sensing Zn2+ with about 20-fold enhancement in aqueous solution, with a characteristic emission band of 4-amino-1, 8-naphthalimide with a green color centered at 550 nm. It was applied successfully to detect Zn2+ in living cells.
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Descubrimiento de Drogas , Colorantes Fluorescentes/química , Zinc/análisis , Teoría Funcional de la Densidad , Relación Dosis-Respuesta a Droga , Colorantes Fluorescentes/síntesis química , Células HeLa , Humanos , Estructura Molecular , Imagen Óptica , Solubilidad , Espectrometría de Fluorescencia , Relación Estructura-Actividad , Agua/químicaRESUMEN
The detection of the HPV L1 protein provides information about the infection status of the virus, reflects the replication status of the HPV virus in cervical cells, and helps understand the regression and progress of cervical lesions. Herein, we report a novel laser desorption ionization mass spectrometry (LDI MS) method for the sensitive detection of the HPV 16 L1 protein, based on non-covalent competitive adsorption between the HPV 16 L1 aptamer and melamine on gold nanoparticles (AuNPs). The intensity of the MS signal corresponding to the mass tag shows a linear relationship with the HPV 16 L1 concentration in the range 2-80 ng mL-1, with a limit of detection (LOD) of 58.8 pg mL-1. Using this method, the HPV 16 L1 protein is quantitatively analyzed in both clinical and vaccine samples. The described method is simple and has high sensitivity and good reliability.
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Proteínas de la Cápside/análisis , Nanopartículas del Metal/química , Proteínas Oncogénicas Virales/análisis , Adsorción , Aptámeros de Nucleótidos/química , Secuencia de Bases , Proteínas de la Cápside/química , Oro/química , Papillomavirus Humano 16/química , Límite de Detección , Espectrometría de Masas/métodos , Proteínas Oncogénicas Virales/química , Vacunas contra Papillomavirus/análisis , ARN/química , Triazinas/químicaRESUMEN
The combination of near infrared spectrum and pattern recognition methods has a wide application prospect in rapid and nondestructive supervision and management of drugs. The traditional identification methods regard the smallest error rate as the goal while the imbalance of classes is ignored. This makes the positive class is overwhelming covered by the negative class and reduces its effect for the classifier, so that the classification results tend to recognize the negative class correctly, which severely affects the identification accuracy. In this paper, we mainly studied the class imbalance problems of true or false drugs via infrared spectral data of its, and then propose a balance cascading and sparse representation based classification method (BC-SRC) by combining the Balance Cascading with SRC. We sampling majority samples from the majority class for several times, which has the same size as minority samples and the majority samples we sampled can contain all the majority class samples entirely (sampling times is ceiling the result of majority samples number divide minority samples number). We can get sets of results, and then obtain the final predict labels form those results. Experiments of three databases achieved on Matlab2012a shows that the method is effective. From the experimental results, it can be seen that the method is superior to the commonly used Partial Least Squares (PLS), Extreme Learning Machine (ELM) and BP. Particularly, for the imbalanced databases, when the imbalance factor is greater than 10, the proposed method has more stable performance with higher classification accuracy than the existing ones mentioned above.
RESUMEN
Near-infrared(NIR)As a fast and non-destructive testing technology, spectroscopy techniques is very suitable for pharmaceutical discrimination. Autoencoder network, as a hot research topic, has drawn widespread attention in machine learning research in recent years. Compared with traditional surface learning algorithm models, Autoencoder network has more powerful modeling capability as a typical deep networks model. Based on the unsupervised greedy layer-wise pre-training, autoencoder trains the network layer by layer while minimizing the error in reconstructing. Each layer is pre-trained with an unsupervised learning algorithm, learning a nonlinear transformation of the input of each layer which is the output of the previous layer. Pre-whitening process could get the inner structural features of the data more effectively. The supervised fine-tuning is followed with the unsupervised pre-training which sets the stage for a final training phase. The deep architecture is fine-tuned with respect to a supervised training criterion with gradient-based optimization. In this paper, firstly, the preprocessing step and pre-whitening transformation were used to treat near-infrared spectroscopy data of erythromycin ethylsuccinate, The pre-whitening transformation would reduce the correlation of the features, which gave each feature the same variance. Experimental results showed that the pre-whitening process had improved the classification accuracy of Sparse Denoising Autoencoder (SDAE) effectively. The SDAE with two hidden layers combined with pre-whitening was used to build the classification model for the identification of counterfeit pharmaceutical. The BP neural networks was compared with SVM algorithm for the classification accuracy and mean absolute difference (MAD). SDAE algorithm had higher classification accuracy than BP neural networks which had the same network structure with the SDAE networks, and SDAE algorithm also performed better than the SVM algorithm when the train datasets achieved a certain amount. As to the generalization performances, SDAE algorithm had less mean absolute difference of classification accuracy than SVM and BP Neural Networks. This result showed that SDAE algorithm could be effectively used to discriminate the counterfeit pharmaceutical.
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Algoritmos , Redes Neurales de la Computación , Aprendizaje Automático , Espectroscopía Infrarroja CortaRESUMEN
Honokiol, a constituent of Magnolia officinalis, has been reported to possess potent anti-cancer activity through targeting multiple signaling pathways in numerous malignancies including acute myeloid leukemia (AML). However, the underlying mechanisms remain to be defined. Here, we report that honokiol effectively decreased enzyme activity of histone deacetylases (HDACs) and reduced the protein expression of class I HDACs in leukemic cells. Moreover, treatment with proteasome inhibitor MG132 prevented honokiol-induced degradation of class I HDACs. Importantly, honokiol increased the levels of p21/waf1 and Bax via triggering acetylation of histone in the regions of p21/waf1 and Bax promoter. Honokiol induced apoptosis, decreased activity of HDACs, and significantly inhibited the clonogenic activity of hematopoietic progenitors in bone marrow mononuclear cells from patients with AML. However, honokiol did not decrease the activity of HDACs and induce apoptosis in normal hematopoietic progenitors from unbilicial cord blood. Finally, honokiol dramatically reduced tumorigenicity in a xenograft leukemia model. Collectively, our findings demonstrate that honokiol has anti-leukemia activity through inhibiting HDACs. Thus, being a relative non-toxic agent, honokiol may serve as a novel natural agent for cancer prevention and therapy in leukemia.
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Apoptosis/efectos de los fármacos , Compuestos de Bifenilo/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Histona Desacetilasas/metabolismo , Leucemia Mieloide/tratamiento farmacológico , Lignanos/farmacología , Enfermedad Aguda , Adulto , Anciano , Animales , Biocatálisis/efectos de los fármacos , Western Blotting , Línea Celular Tumoral , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Medicamentos Herbarios Chinos/farmacología , Femenino , Humanos , Células K562 , Leucemia Mieloide/genética , Leucemia Mieloide/metabolismo , Masculino , Ratones Desnudos , Persona de Mediana Edad , Complejo de la Endopetidasa Proteasomal/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
MYC dysregulation, including MYC gene rearrangement and Myc protein overexpression, is of increasing clinical importance in diffuse large B-cell lymphoma (DLBCL). However, the roles of MYC and the relative importance of rearrangement vs overexpression remain to be refined. Gaining knowledge about the tumor biology associated with MYC dysregulation is important to understand the roles of MYC and MYC-associated biology in lymphomagenesis. In this study, we determined MYC rearrangement status (n=344) and Myc expression (n=535) in a well-characterized DLBCL cohort, individually assessed the clinical and pathobiological features of patients with MYC rearrangement and Myc protein overexpression, and analyzed the prognosis and gene expression profiling signatures associated with these MYC abnormalities in germinal center B-cell-like and activated B-cell-like DLBCL. Our results showed that the prognostic importance of MYC rearrangement vs Myc overexpression is significantly different in germinal center B-cell-like vs activated B-cell-like DLBCL. In germinal center B-cell-like DLBCL, MYC-rearranged germinal center B-cell-like DLBCL patients with Myc overexpression significantly contributed to the clinical, biological, and prognostic characteristics of the overall Myc-overexpressing germinal center B-cell-like DLBCL group. In contrast, in activated B-cell-like DLBCL, the occurrence, clinical and biological features, and prognosis of Myc overexpression were independent of MYC rearrangement. High Myc levels and Myc-independent mechanisms, either tumor cell intrinsic or related to tumor microenvironment, conferred significantly worse survival to MYC-rearranged germinal center B-cell-like DLBCL patients, even among Myc(high)Bcl-2(high) DLBCL patients. This study provides new insight into the tumor biology and prognostic effects associated with MYC dysregulation and suggest that detection of both MYC translocations and evaluation of Myc and Bcl-2 expression is necessary to predict the prognosis of DLBCL patients.
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Genes myc/genética , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Reordenamiento Génico , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-myc/genética , Rituximab/administración & dosificación , Transcriptoma , Vincristina/administración & dosificaciónRESUMEN
This study aimed to explore the tumor-promoting function of esophageal cancer-related gene 4 (ECRG4) in the papillary thyroid cancer and its related mechanism. ECRG4 Messenger RNA (mRNA) and protein expression analysis in papillary thyroid cancer tissues was performed by quantitative real-time PCR (Q-RT-PCR), Western blot, and immunohistochemistry methods. Ten pairs of fresh samples from the papillary thyroid carcinoma patients were analyzed for ECRG4 promoter CpG island methylation status by bisulfite sequencing analysis. We also transfected ECRG4 into papillary thyroid cancer cell lines W3 and K1 with lentivirus and analyzed ECRG4 functions through evaluating the changes of the proliferation activity, the cell cycle, and the cell apoptosis rate of these transformed cells. We found that ECRG4 expression was upregulated in most papillary thyroid cancer samples (70.0%, 28 out of 40 papillary thyroid cancer samples) on the protein level, and the ECRG4 mRNA level was also enhanced in tumor tissues compared to their matched nontumor tissues. CpG islands around the ECRG4 promoter region were demethylated in the papillary thyroid cancer samples. At the same time, the upregulated expression of ECRG4 in papillary thyroid cancer cell lines W3 and K1 could promote both the proliferation activity and the cell cycle transition from the G1 phase into the G2 but could not affect the cell apoptosis rate. The expression of ECRG4 is frequently upregulated in a papillary thyroid carcinoma through the demethylation mechanism of CpG islands in the gene promoter region, and the ECRG4 has a tumor-promoting function through inducing the cell cycle transition from the G1 phase to the G2 in papillary thyroid carcinoma cells.
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Carcinogénesis/genética , Carcinoma/genética , Metilación de ADN/genética , Proteínas de Neoplasias/biosíntesis , Neoplasias de la Tiroides/genética , Apoptosis/genética , Carcinoma/patología , Carcinoma Papilar , Línea Celular Tumoral , Proliferación Celular/genética , Islas de CpG/genética , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Fase G2/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas de Neoplasias/genética , Regiones Promotoras Genéticas , ARN Mensajero/biosíntesis , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Proteínas Supresoras de TumorRESUMEN
Drug safety has become a very important subject, and more countries have joined in the fight against counterfeit drugs. This study demonstrated a non-invasive Raman spectroscopy method that could be utilized for screening liquid injectable drugs for spurious/falsely-labeled/falsified/counterfeit medical products (SFFCs). Two problems were solved to remove the blocks in identification and quantitation: one problem was the weak API signal extraction from the non-invasive Raman spectra and the other was the problem of Raman absolute measurement. Principal component analysis (PCA) and classical least square (CLS) algorithms were performed to establish the models. Water was chosen as the "internal standard" to normalize the spectra to solve the problem of Raman absolute measurement. The results showed that the 11 positive samples and 66 negative samples were all well identified with a threshold of 0.95. One of the positive samples contained the excipient propylene glycol, which was identified successfully at the same time. The accuracy of quantitative results was approximately 5% for doxofylline liquid injectables and about 10% for the low-concentration and big glass bottle-containers of Levofloxacin Lactate and Sodium Chloride Injections as compared to the results using an HPLC method, this is satisfactory for fast screening of SFFCs. In conclusion, with the development of a database of identification and quantitation models, this method may determine liquid injectable drugs in a fast and non-invasive way and become one of the most powerful weapons against SFFCs. Graphical Abstract á .
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Vías de Administración de Medicamentos , Espectrometría Raman/métodos , Algoritmos , Levofloxacino/administración & dosificación , Análisis de Componente Principal , Teofilina/administración & dosificación , Teofilina/análogos & derivadosRESUMEN
This study aims to explore the apoptotic function of shikonin on the papillary thyroid cancer cells and the related mechanism. The papillary thyroid cancer cell lines K1 and W3 and thyroid follicular epithelial cells NTHY-ORI 3-1 were treated with different concentrations of shikonin. Cell proliferation was tested. Morphological changes of the apoptotic cells were observed by Hoechst 33342 staining. The apoptosis rate of the papillary thyroid cancer cells was measured with flow cytometry. Changes of the cell cycle were explored. The mitochondrial membrane potential changes were analyzed after JC-1 staining. Bcl-2 family proteins and caspase-3 expression with shikonin treatment was analyzed by real-time fluorescence polymerase chain reaction (PCR). Cell proliferation of K1 and W3 was inhibited by shikonin, and the inhibition was dose-time dependent. Papillary thyroid carcinoma cells treated by shikonin had no obvious cell cycle arrest but were observed with the higher apoptosis rate and the typical apoptotic morphological changes of the cell nucleus. JC-1 staining showed that shikonin reduced the mitochondrial membrane potential of papillary thyroid carcinoma cells. Real-time PCR results showed that shikonin significantly increased Bax and caspase-3 expression and upregulated Bcl-2 expression in a dose-dependent manner in papillary thyroid carcinoma cells. However, the NTHY-ORI 3-1 was almost not affected by shikonin treatment. Shikonin can inhibit K1 and W3 cell proliferation in a dose- and time-dependent manner, enhance Bax levels, reduce anti-apoptotic protein Bcl-2 levels, result in decreasing mitochondrial membrane potential and activating caspase-3 enzyme, and finally lead to apoptosis.
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Antiinflamatorios no Esteroideos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Naftoquinonas/farmacología , Neoplasias de la Tiroides/metabolismo , Carcinoma Papilar , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citometría de Flujo , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Cáncer Papilar TiroideoRESUMEN
This study aims to explore the apoptotic function of apigenin on the gastric cancer cells and the related mechanism. The gastric cancer cell lines HGC-27 and SGC-7901, and normal gastric epithelial cell line GES1 were treated with different concentrations of apigenin. Cell proliferation was tested. Morphological changes of the apoptotic cells were observed after Hoechst33342 staining. The apoptosis rate of the gastric cancer cells were measured with flow cytometry. Changes of the cell cycle were explored. The mitochondrial membrane potential changes were analyzed after JC-1 staining. Bcl-2 family proteins and caspases-3 expression with apigenin treatment was analyzed by real-time PCR. Cell proliferation of HGC-27 and SGC-7901 was inhibited by apigenin, and the inhibition was dose-time-dependent. Gastric carcinoma cells treated by apigenin had no obvious cell cycle arrest, but were observed with the higher apoptosis rate and the typical apoptotic morphological changes of the cell nucleus. JC-1 staining showed that apigenin could reduce mitochondrial membrane potential of gastric carcinoma cells. Real-time PCR results showed that apigenin significantly increased caspase-3 and Bax expression level, and down-regulated Bcl-2 expression in a dose-dependent manner in gastric carcinoma cells. However, the GES1 was almost not affected by apigenin treatment. Apigenin can inhibit cell lines HGC-27 and SGC-7901 proliferation in a time and dose-dependent manner, reduce anti-apoptotic protein Bcl-2 levels, enhance apoptosis-promoting protein Bax level, result in mitochondrial membrane potential decreasing and caspase-3 enzyme activating, then lead to cell apoptosis.
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Apigenina/farmacología , Apoptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Núcleo Celular/patología , Proliferación Celular/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/fisiología , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/patologíaRESUMEN
The therapeutic potential of baicalein against hepatoma cells was evaluated in vitro and in vivo. In cell viability assays, baicalein showed significant cytotoxicity against the hepatocellular carcinoma cell lines H22, Bel-7404, and Hep G2 and moderate cytotoxicity against immortalized human hepatocytes. Baicalein induced G0/G1-phase arrest in hepatocellular carcinoma cells, inhibited AKT, and promoted the degradation of ß-catenin and cyclin D1 without activation of GSK-3ß. Furthermore, baicalein significantly inhibited H22 xenograft tumor growth without causing obvious adverse effects on weight or liver and spleen weight indexes in ICR mice. Immunohistochemical analysis showed that the inhibition of tumor growth in baicalein-treated mice was associated with decreased AKT, ß-catenin, and cyclin D1 expression ex vivo. Our data indicate that baicalein might regulate cyclin D1 transcription via a ß-catenin-dependent mechanism, leading to cell cycle arrest at G0/G1 phase and impaired cancer cell proliferation. These results suggest that baicalein is a potential candidate for the treatment of hepatocellular carcinoma.
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Carcinoma Hepatocelular/patología , Flavanonas/farmacología , Neoplasias Hepáticas/patología , Animales , Carcinoma Hepatocelular/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina D1/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Ratones Endogámicos ICR , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/metabolismoRESUMEN
Powder X-ray diffraction (PXRD) technology combined with cluster analysis method was used to classify 75 batches of crystalline ceftriaxone sodium into subtypes, the crystalline characteristics of each subtype were measured with scanning electron microscope (SEM). By comparing some parameters of these subtypes correlated to crystallization process of ceftriaxone sodium, such as salification rate, water content in different subtypes, as well as by studying different lattice stabilities, different compatibilities with rubber closures during accelerated stability tests, the key point to improve the quality of domestic ceftriaxone sodium was disclosed. The results of this paper indicated that the fine structure of the products could be controlled well by improving the salification and crystallization process. As a result, the subtype II of ceftriaxone sodium with high stability can be produced.
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Ceftriaxona/química , Ceftriaxona/clasificación , Cristalización , Microscopía Electrónica de Rastreo , Polvos , Agua , Difracción de Rayos XRESUMEN
This study assessed the presence of the genotoxic impurity 1-methyl-4-nitrosopiperazine (MNP) in 27 batches of rifampicin capsules obtained from 11 manufacturers in China. While they were below the temporary limit of 5â¯ppm set by the US Food and Drug Administration, the observed levels (0.33-2.36â¯ppm) exceeded the acceptable threshold of 0.16â¯ppm. Building upon preliminary findings and degradation experiments, we concluded that MNP is a by-product of the oxidative degradation of rifampicin or is introduced via oxidation or nitrosation during the synthesis process involving 1-methyl-4-aminopiperazine. The pathways of MNP formation were confirmed in this study. Furthermore, we observed that the addition of antioxidants, sealed storage, and selection of dominant crystal forms can aid in controlling MNP levels.
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Contaminación de Medicamentos , Piperazinas , Rifampin , Rifampin/química , Rifampin/análisis , Contaminación de Medicamentos/prevención & control , Piperazinas/química , Piperazinas/análisis , Mutágenos/química , Mutágenos/análisis , Oxidación-Reducción , Cápsulas , China , Antioxidantes/química , Antioxidantes/análisisRESUMEN
Dezocine, which is well-known as an analgesic, had about 45% share of the Chinese opioid analgesic market. Since drug products containing impurities could bring serious health consequences, it was important to control the generation of impurities and degradation products in the dezocine product. In this study, two kinds of photodegradation products (i.e., degradation product 1 and degradation product 2) in the dezocine injection were isolated using high-performance liquid chromatography. The possible structures of the photodegradation products were identified using both high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. In addition, the possible generation mechanism showed that degradation product 1 was the oxidation product of dezocine, and degradation product 2 was the coupled dimer of dezocine. Finally, we found that the degradation rate of dezocine increased with the increase in light intensity. Moreover, the degradation of dezocine easily occurred under ultraviolet light in comparison with visible light. A deeper insight into the generation of the photodegradation products in the dezocine injection would directly contribute to the safety of drug therapy based on the dezocine injection by minimizing the degradant/impurity-related adverse effects of drug preparations.