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Two coordination polymers (CPs), [Zn5(L)2(phen)5](1) and [Cd2(HL)(2,2-bpy)(H2O)3](2), were synthesized by using 2',3,3',5,5'-Diphenyl ether pentacarboxylic acid (H5L), phenanthroline (phen), and 2,2'-bipyridine (2,2'-bpy) under hydrothermal conditions. The L5- ligand adopts the µ6-к2: к2: к1: к1: к1: к1 mode in 1 and the µ5-к2: к2: к2: к2: к1 mode in 2. Sensing experiments show that 1 and 2 are fluorescence probes with high sensitivity and rapid detection of nitro explosives, antibiotics, and pesticides. In order to verify the ability of 2 to detect FLU in actual samples, we performed a spiked recovery experiment in green pepper water. The spiked recoveries were 97.77-101.18 %. Interestingly, because H5L is not completely deprotonated in 2, there is abundant hydrogen bonding, which makes the fluorescence quenching rate higher and the detection limit lower. The possible fluorescence quenching mechanism of 1 and 2 can be explained by their UV-VIS absorption spectra and orbital energy levels.
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The study aims to lessen the monetary burden on patients and society by decreasing the price of proprietary drugs used in leukemia therapy. Flow cytometry, reverse transcription polymerase chain reaction, western blot, and a patient-derived xenograft mouse model were used to confirm the therapeutic effect of Pinellia ternata extract on leukemia. Three types of leukemia cells (K562, HL-60, and C8166 cell lines) were found to undergo early apoptosis (P ≤ .05) after being exposed to P. ternata extract, as measured by flow cytometry. Reverse transcription polymerase chain reaction results showed that P. ternata extract at both middle (300 µg/mL) and high (500 µg/mL) concentrations was able to down-regulate Bcl-2 and upregulate mRNA expression of Bax and caspase-3. In the patient-derived xenograft mouse model formed by BALB/c-nu/nu nude mice, immunohistochemistry indicated that P. ternata extract effectively suppressed the proliferation of leukemia cells. Therefore, P. ternata extract at 300 µg/mL and 500 µg/mL could effectively inhibit myeloid and lymphocytic leukemia cell proliferation and promote leukemia cell apoptosis by regulating Bax/Bcl-2 and caspase-3.
Assuntos
Leucemia , Pinellia , Humanos , Camundongos , Animais , Caspase 3/genética , Caspase 3/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Pinellia/metabolismo , Camundongos Nus , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Apoptose , Leucemia/tratamento farmacológico , Proliferação de CélulasRESUMO
Surface plasmon coupled emission (SPCE), a novel surface-enhanced fluorescence technique, can generate directional and amplified radiation by the intense interaction between fluorophores and surface plasmons (SPs) of metallic nanofilms. For plasmon-based optical systems, the strong interaction between localized and propagating SPs and "hot spot" structures show great potential to significantly improve the electromagnetic (EM) field and modulate optical properties. Au nanobipyramids (NBPs) with two sharp apexes to enhance and restrict the EM field were introduced through electrostatic adsorption to achieve a mediated fluorescence system, and the emission signal enhancement was realized by factors over 60 compared with the normal SPCE. It has been demonstrated that the intense EM field produced by the NBPs assembly is what triggered the unique enhancement of SPCE by Au NBPs, which effectively overcomes the inherent signal quenching of SPCE for ultrathin sample detection. This remarkable enhanced strategy offers the chance to improve the detection sensitivity for plasmon-based biosensing and detection systems, and expand the range of applications for SPCE in bioimaging with more comprehensive and detailed information acquisition. The enhancement efficiency for various emission wavelengths was investigated in light of the wavelength resolution of SPCE, and it was discovered that enhanced emission for multi-wavelength could be successfully detected through the different emission angles due to the angular displacement caused by wavelength change. Benefit from this, the Au NBP modulated SPCE system was employed for multi-wavelength simultaneous enhancement detection under a single collection angle, which could broaden the application of SPCE in simultaneous sensing and imaging for multi-analytes, and expected to be used for high throughput detection of multi-component analysis.
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Corantes Fluorescentes , Ressonância de Plasmônio de Superfície , Ressonância de Plasmônio de Superfície/métodos , Corantes Fluorescentes/químicaRESUMO
Wernekink commissure syndrome is a rare midbrain syndrome with bilateral cerebellar dysfunction,eye movement disorder,and palatal myoclonus.Few cases of this syndrome have been reported in China,let alone those combined with hallucinations and involuntary groping.This paper reports the diagnosis and treatment of a case of Wernekink commissure syndrome with hallucinations and involuntary groping,aiming to enrich the knowledge about this disease for clinicians.
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Mesencéfalo , Transtornos da Motilidade Ocular , Humanos , Transtornos da Motilidade Ocular/diagnóstico , Medula Espinal , Síndrome , AlucinaçõesRESUMO
Neuroblastoma has obvious heterogeneity. It is one of the few undifferentiated malignant tumors that can spontaneously degenerate into completely benign tumors. However, for its high-risk type, even with various intensive treatment options, the prognosis is still unsatisfactory. At the same time, a large number of research data show that the abnormal amplification and high-level expression of the MYCN gene are positively correlated with the malignant progression, poor prognosis, and mortality of neuroblastoma. In this context, this article explores the role of the N-Myc, MYCN gene expression product on its target genes related to the cell cycle and reveals its regulatory network in promoting tumor proliferation and malignant progression. We hope it can provide ideas and direction for the research and development of drugs targeting N-Myc and its downstream target genes.
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Neuroblastoma , Proteínas Nucleares , Humanos , Proteínas Nucleares/metabolismo , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Genes myc , Ciclo Celular/genética , Neuroblastoma/patologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular TumoralRESUMO
WHAT IS KNOWN AND OBJECTIVES: Ciclosporin (CsA), a potent immunosuppressive agent used to prevent graft-versus-host disease in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, is characterized by large inter-individual variability and a narrow therapeutic range. The aim of this study was to develop a population pharmacokinetic model for CsA in Chinese allo-HSCT recipients and to identify covariates influencing CsA pharmacokinetics. METHODS: A total of 758 retrospective drug monitoring data points were collected after intravenous infusion or oral administration of CsA from 59 patients. Population pharmacokinetic analysis was performed using nonlinear mixed effects modelling expressed by differential equations. Monte Carlo simulation was applied to optimize dosage regimens. The final model was validated using bootstrap and normalized prediction distribution errors. RESULTS AND DISCUSSION: The results showed that the daily CsA dose, haematocrit, total bile acid, C-reactive protein (CRP) and co-administration of triazole antifungal agent were identified as significant covariates for clearance (CL) of CsA. The typical value of CL was 19.8 L/h with an inter-individual variability of 13.1%. The volume of distribution was 1340 L. Bioavailability was 67.2% with an inter-individual variability of 8.5%. Dosing simulation based on the developed model indicated that patients with high CRP concentration required a higher daily dose to attain the therapeutic trough concentration. The influence of CRP ultimately on the therapy outcome of CsA is not clear, which needs further study. WHAT IS NEW AND CONCLUSION: CRP concentration was identified as a novel marker associated with CsA pharmacokinetics, which should be considered when determining the appropriate dosage of CsA in allo-HSCT recipients.
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Ciclosporina , Transplante de Células-Tronco Hematopoéticas , Proteína C-Reativa , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores , Modelos Biológicos , Estudos Retrospectivos , TransplantadosRESUMO
1. We aimed to establish a population pharmacokinetic (PK) model of tacrolimus and identify clinical covariates, especially the genetic polymorphisms of CYP3A5, ABCB1 and POR*28 that affected the PK to prevent fluctuation in the trough concentration of tacrolimus during the early period after renal transplantation. 2. Tacrolimus trough concentration, clinical data and CYP3A5/ABCB1/POR28 genotypes were retrospectively collected from 234 kidney transplant recipients during the first month post-transplantation. The population PK model was built using the non-linear mixed effects modeling software NONMEM. Dosing simulation was performed based on the final model. 3. A one-compartment model with first-order absorption and elimination was used to characterize the PK of tacrolimus. Among the genotypes, only CYP3A5 genotype was confirmed to have clinical significance. The final model describing CL/F (l/h) was as follows: 23.3 × ( HCT / 0.309 ) - 0.445 × [ ( 0.897 , i f POD > 10 ) o r ( 1 , i f POD ≤ 10 ) ] × ( 0.657 , i f CYP 3 A 5 * 3 / * 3 genotype ) . The inter-individual variability in CL/F was 21.9%. Monte Carlo simulation based on the final model was carried out to determine the optimal dosage regimen. 4. CYP3A5 genotype, post-operative day and hematocrit were confirmed as critical PK factors of tacrolimus. The model could be used to accurately predict individual PK parameters of tacrolimus and provide valuable insights into the dosage optimization.
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Citocromo P-450 CYP3A/genética , Imunossupressores/farmacocinética , Tacrolimo/farmacocinética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Humanos , Transplante de Rim , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We experimentally demonstrated a diode-pumped 587 fs ultrafast laser by using an a-cut Nd:CaYAlO4 crystal. Pumped by an 808 nm fiber-coupled laser diode, a stable continuous-wave mode-locked ultrafast laser was achieved with a semiconductor saturable absorber. The ultrafast pulses had a repetition rate of 75 MHz at the center wavelength of 1080.8 nm. A maximum average output power of the mode-locked laser reached 375 mW delivering a slope efficiency of 9%.
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A simple and sensitive liquid chromatography method with diode array detector was established for simultaneous determination of 11 components (geniposidic acid, chlorogenic acid, caffeic acid, geniposide, luteoloside, isochlorogenic acid C, baicalin, luteolin, wogonoside, baicalein and wogonin) in various commercial Yinzhihuang preparations and their herbs by optimizing the extraction, separation and analytical conditions. Eleven components were identified on the basis of their retention times and mass spectra. Chromatographic separation was performed on a C18 analytical column with a gradient elution of acetonitrile and 0.1% formic acid water solution at a flow rate of 1.0 mL/min. The linearity, precision and accuracy of the data obtained were acceptable. The method was used to analyze four Yinzhihuang preparations (powder, capsule, oral liquid and injection) and related herbs (Radix Scutellariae, Flos Lonicerae, Herba Artemisiae Scopariae and Fructus gardeniae). Results suggested that the optimized method could be considered as a good approach to control the quality of Yinzhihuang preparations and their herbs.
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Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Espectrofotometria Ultravioleta/métodos , Reprodutibilidade dos TestesRESUMO
Rhizoma alismatis (the rhizome of Alisma orientalis) polysaccharides (RAP) have been reported to have a variety of important biological activities. However, effective extraction of RAP has been an unsolved issue. In this study, we used an ultrasound method for high yield extraction of RAP and optimized the conditions using the response surface methodology (RSM). Following multiple regression analyses of the experimental results, we applied the 3-D response surface and the contour plots to determine the optimal conditions, which were found to be ultrasound treatment at 76.1°C for 75.2 min, and water to material ratio at 30.1 ml/g. Under such conditions, the yield was 6.90% which was much higher than traditional hot water extraction yield (3.41%). The fractionated RAPs following stepwise ethanol precipitation showed strong antioxidant activities. The results indicated that ultrasound extraction was a very effective method for the extraction of RAP and the polysaccharides could be explored as a potential antioxidant agent for use in medicine or functional food.
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Alisma/química , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Polissacarídeos/isolamento & purificação , Ultrassom/métodos , Análise de Variância , Animais , Compostos de Bifenilo/química , Eritrócitos/efeitos dos fármacos , Sequestradores de Radicais Livres/química , Hemólise/efeitos dos fármacos , Temperatura Alta , Masculino , Peso Molecular , Picratos/química , Polissacarídeos/farmacologia , Ratos Wistar , Reprodutibilidade dos Testes , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de Tempo , Água/farmacologiaRESUMO
Three kinds of chitooligosaccharides (COS) with different degrees of deacetylation were prepared and named MD90, MD70 and MD50, respectively. Antioxidation, antiglycation and nitric oxide (NO) promotion in erythrocyte of these samples were investigated. The results showed that COS, especially MD90 had obviously inhibitory effects on oxidation and glycation. In addition, MD90 displayed stronger effect on increasing endogenous NO content than both MD70 and MD50, whose degrees of deacetylation were lower. The results indicated that amino group in COS has a certain effect on the activities of COS. As COS have a conformed activity to treat diabetes, the results of this study may be meaningful for further understanding the mechanism of the action.