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1.
Clin. transl. oncol. (Print) ; 26(3): 756-764, mar. 2024.
Artigo em Inglês | IBECS | ID: ibc-230805

RESUMO

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan–Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3–5) to 11 months (95% CI 8–12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38–50) and 25% (95 CI 20–30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19–29) and 6% (95 CI 3–9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88–2.72, p value < 0.001) was an adverse independent prognostic factor for patients (AU)


Assuntos
Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , Estudos Prospectivos , Qualidade de Vida , Prognóstico
2.
Clin Transl Oncol ; 26(3): 756-764, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37606846

RESUMO

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan-Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3-5) to 11 months (95% CI 8-12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38-50) and 25% (95 CI 20-30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19-29) and 6% (95 CI 3-9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88-2.72, p value < 0.001) was an adverse independent prognostic factor for patients. This study concludes that CDS prolonged survival in patients with gastric cancer with liver metastases. Due to the lack of information on the quality of life, biomarkers, targeted therapies, and immunotherapy in the SEER database, the observed improved survival rates following CDS of hepatic metastasis from gastric cancer requires prospective studies that take these factors into account to properly address the survival advantages and impact on quality of life of such a method.


Assuntos
Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Prognóstico , Neoplasias Hepáticas/secundário
3.
Small ; 18(49): e2203659, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36310137

RESUMO

Photoimmunotherapy is attractive for cancer treatment due to its spatial controllability and sustained responses. This work presents a ferrocene-containing Ir(III) photosensitizer (IrFc1) that can bind with transferrin and be transported into triple-negative breast cancer (TNBC) cells via a transferrin receptor-mediated pathway. When the ferrocene in IrFc1 is oxidized by reactive oxygen species, its capability to photosensitize both type I (electron transfer) and type II (energy transfer) pathways is activated through a self-amplifying process. Upon irradiation, IrFc1 induces the generation of lipid oxidation to cause ferroptosis in TNBC cells, which promotes immunogenic cell death (ICD) under both normoxia and hypoxia. In vivo, IrFc1 treatment elicits a CD8+ T-cell response, which activates ICD in TNBC resulting in enhanced anticancer immunity. In summary, this work reports a small molecule-based photosensitizer with enhanced cancer immunotherapeutic properties by eliciting ferroptosis through a self-amplifying process.


Assuntos
Neoplasias , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/farmacologia , Irídio , Receptores da Transferrina
4.
Nutrients ; 14(12)2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35745162

RESUMO

Obesity is an important public health problem nowadays. Long-term obesity can trigger a series of chronic diseases and impair the learning and memory function of the brain. Current studies show that scientific exercise can effectively improve learning and memory capacity, which also can provide benefits for obese people. However, the underlying mechanisms for the improvement of cognitive capacity under the status of obesity still need to be further explored. In the present study, the obesity-induced cognition-declined model was established using 4-week-old mice continuously fed with a high-fat diet (HFD) for 12 weeks, and then the model mice were subjected to an 8-week swimming intervention and corresponding evaluation of relevant indicators, including cognitive capacity, inflammation, insulin signal pathway, brain-derived neurotrophic factor (BNDF), and apoptosis, for exploring potential regulatory mechanisms. Compared with the mice fed with regular diets, the obese mice revealed the impairment of cognitive capacity; in contrast, swimming intervention ameliorated the decline in cognitive capacity of obese mice by reducing inflammatory factors, inhibiting the JNK/IRS-1/PI3K/Akt signal pathway, and activating the PGC-1α/BDNF signal pathway, thereby suppressing the apoptosis of neurons. Therefore, swimming may be an important interventional strategy to compensate for obesity-induced cognitive impairment.


Assuntos
Disfunção Cognitiva , Resistência à Insulina , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Dieta Hiperlipídica/efeitos adversos , Hipocampo/metabolismo , Humanos , Inflamação/metabolismo , Camundongos , Camundongos Obesos , Obesidade/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Natação
5.
Environ Sci Pollut Res Int ; 29(25): 37359-37374, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35064512

RESUMO

Municipal solid waste (MSW) is a highly heterogeneous porous medium that contains a variety of components and has complex pores and solid structures. Macroscale experiments are insufficient to describe the hydraulic and mechanical properties of MSW, especially for preferential flow in pores and the reinforcing effect of solids. For a deep understanding of the microscale structure of MSW, CT scanning tests were carried out on two kinds of samples prepared in the laboratory and drilled in landfills. MSW images were divided into pores and solids through dynamic threshold segmentation and morphological denoising methods. The distributions of pore size and structural solid angle were calculated by the maximum inscribed sphere (MIS) algorithm and angle statistical algorithm based on the surface model, respectively. According to the pore-size distribution, the pores were divided into large (diameter > 1 mm), medium (1 mm > diameter > 0.1 mm), and small (diameter < 0.1 mm) pores in MSW. Under a vertical stress of 50 kPa, the porosities of the large, medium, and small pores were 35%, 12%, and 26%, respectively. As the vertical stress increased to 400 kPa, the porosity of large pores decreased significantly to 15%, while the porosities of medium and small pores remained almost unchanged. In addition, the structural solid angle tended to be horizontal under compression, but its influence was limited. The structural solid angle was mainly concentrated at approximately 30-32°. The probability distribution of the structural solid angle could be well fitted using the Gauss function.


Assuntos
Eliminação de Resíduos , Resíduos Sólidos , Eliminação de Resíduos/métodos , Resíduos Sólidos/análise , Tomografia , Tomografia Computadorizada por Raios X , Instalações de Eliminação de Resíduos
6.
World J Clin Cases ; 9(16): 3848-3857, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34141741

RESUMO

BACKGROUND: Conventional recanalization techniques may fail in patients with completely occluded superior vena cava (SVC). AIM: To analyze the effectiveness and complications of sharp recanalization for completely occluded SVC. METHODS: This was a retrospective study of patients that underwent puncture and recanalization of the SVC between January 2016 and December 2017 at our hospital. Sharp recanalization was performed using the RUPS-100 system. The patients were followed for 12 mo. The main outcomes were the patency rate of SVC and arteriovenous fistula flow during dialysis. RESULTS: The procedure was successful in all 14 patients (100%). Blood pressure in the distal SVC decreased in all 14 cases (100%) from 26.4 ± 2.7 cmH2O to 14.7 ± 1.3 cmH2O (P < 0.05). The first patency rates of the SVC at 24 h and at 3, 6, 9 and 12 mo after sharp recanalization were 100%, 92.9%, 85.7%, 78.6% and 71.4%, respectively. There were two (14.3%) severe, one (7.1%) moderate and one (7.1%) minor complication. The severe complications included one case of pericardial tamponade and one case of hemothorax. CONCLUSION: The results suggest that sharp recanalization can be an additional tool to extend or renew the use of an occluded upper extremity access for hemodialysis. This could be of use in patients with long-term maintenance hemodialysis in whom the maintenance of central venous access is often a challenge.

7.
Adv Sci (Weinh) ; 7(1): 1901992, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31921566

RESUMO

Ruthenium complexes are promising photosensitizers (PSs), but their clinical applications have many limitations. Here, a multifunctional nano-platform PDA-Pt-CD@RuFc formed by platinum-decorated and cyclodextrin (CD)-modified polydopamine (PDA) nanoparticles (NPs) loaded with a ferrocene-appended ruthenium complex (RuFc) is reported. The NPs can successfully deliver RuFc to the tumor sites. The release of RuFc from the NPs can be triggered by low pH, photothermal heating, and H2O2. The combined photodynamic and photothermal therapy (PDT-PTT) mediated by PDA-Pt-CD@RuFc NPs can overcome the hypoxic environment of tumors from several aspects. First, the platinum NPs can catalyze H2O2 to produce O2. Second, vasodilation caused by photothermal heating can sustain the oxygen supplement. Third, PDT exerted by RuFc can also occur through the non-oxygen-dependent Fenton reaction. Due to the presence of PDA, platinum NPs, and RuFc, the nanosystem can be used in multimodal imaging including photothermal, photoacoustic, and computed tomography imaging. The NPs can be excited by the near-infrared two-photon light source. Moreover, the combined treatment can improve the tumor microenvironments to obtain an optimized combined therapeutic effect. In summary, this study presents a tumor-microenvironment-adaptive strategy to optimize the potential of ruthenium complexes as PSs from multiple aspects.

8.
J Clin Pharm Ther ; 45(3): 419-429, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31954070

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Corticosteroids are recommended by almost all international guidelines for the management of exacerbations of chronic obstructive pulmonary disease (COPD). Nevertheless, due to their side effects, there are still concerns regarding the use of systemic corticosteroids (SCs). The Global Initiative for Chronic Obstructive Lung Disease guideline states nebulized budesonide (NB) may be a suitable alternative to SCs for treating COPD exacerbations. We conducted this study to systematically compare the efficacies of NB and SCs by using a meta-analysis. METHODS: PubMed, EMBASE and Cochrane Library databases were searched from database inception to 10 October 2019. Our main end points were change in pulmonary function and blood gas analysis. Secondary end points were numbers of exacerbations and hyperglycaemia. RESULTS AND DISCUSSION: Of 645 identified studies, 6 were eligible and were included in our analysis (N = 867 participants). Compared with SCs, NB was non-inferior on the change in FEV1 %predicted at 24 hours, 48-72 hours and 5-7 days; FEV1 at 5-7 days; FEV1 /FVC at 7 days. For blood gas analysis, our meta-analysis indicated that PaO2 , PaCO2 at 24 hours, 48-72 hours and 7-10 days and SaO2 at 24 hours and 7-10 days showed a non-significant difference in both groups, whereas the SaO2 was significant higher in NB group at 48-72 hours after treatment. Hyperglycaemia was less frequent with NB (odds ratio, 0.1; 95% CI, 0.01-0.85; P = .04). WHAT IS NEW AND CONCLUSION: Based on our meta-analysis, NB was not inferior to SCs when used in the treatment of COPD exacerbations. However, additional well-designed prospective studies are needed to identify the optimal dose of nebulized budesonide and the effects of nebulized budesonide in outpatients, or patients in ICU settings.


Assuntos
Corticosteroides/administração & dosagem , Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Humanos , Nebulizadores e Vaporizadores
9.
Chemistry ; 25(28): 7012-7022, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-30913329

RESUMO

The chemo-anti-inflammatory strategy is attracting ever more attention for the treatment of cancer. Here, two cyclometalated IrIII complexes Ir2 and Ir3 formed by conjugation of Ir1 with two antiphlogistics (aspirin and salicylic acid) have been designed. Ir2 and Ir3 exhibit higher antitumor and anti-inflammatory potencies than a mixture of Ir1 and aspirin/salicylic acid. We show that they can be hydrolyzed, accumulate in mitochondria, and induce mitochondrial dysfunction. Due to their intense long-lived phosphorescence, Ir2 and Ir3 can track mitochondrial morphological changes. Phosphorescence lifetime imaging shows that Ir2 and Ir3 can aggregate during mitochondrial dysfunction. As expected, Ir2 and Ir3 exhibit immunomodulatory properties by regulating the activity of immune factors. Both Ir2 and Ir3 can induce caspase-dependent apoptosis and caspase-independent paraptosis and inhibit several events related to metastasis. Moreover, Ir2 and Ir3 show potent tumor growth inhibition in vivo. Our study demonstrates that the combination of mitochondrial-targeting and immunomodulatory activities is feasible to develop multifunctional metal-based anticancer agents.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Aspirina/uso terapêutico , Complexos de Coordenação/uso terapêutico , Imunomodulação/efeitos dos fármacos , Irídio/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Aspirina/química , Aspirina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Feminino , Humanos , Irídio/química , Irídio/farmacologia , Medições Luminescentes/métodos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Imagem Óptica/métodos
10.
J Med Chem ; 62(7): 3311-3322, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30816710

RESUMO

Emerging studies have shown that mitochondrial DNA (mtDNA) is a potential target for cancer therapy. Herein, six cyclometalated Ir(III) complexes Ir1-Ir6 containing a series of extended planar diimine ligands have been designed and assessed for their efficacy as anticancer agents. Ir1-Ir6 show much higher cytotoxicity than cisplatin and they can effectively localize to mitochondria. Among them, complexes Ir3 and Ir4 with dipyrido[3,2- a:2',3'- c]phenazine (dppz) ligands can bind to DNA tightly in vitro, intercalate to mtDNA in situ, and induce mtDNA damage. Ir3- and Ir4-impaired mitochondria exhibit decline of mitochondrial membrane potential, disability of adenosine triphosphate generation, disruption of mitochondrial energetic and metabolic status, which subsequently cause protective mitophagy, G0/G1 phase cell cycle arrest, and apoptosis. In vivo antitumor evaluations also show that Ir4 can inhibit tumor xenograft growth effectively. Overall, our work proves that targeting the mitochondrial genome may present an effective strategy to develop metal-based anticancer agents to overcome cisplatin resistance.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Dano ao DNA , DNA Mitocondrial/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Irídio/química , Células A549 , Animais , Complexos de Coordenação/química , Cristalografia por Raios X , DNA Mitocondrial/metabolismo , Células HeLa , Humanos , Ligantes , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
J Pharm Biomed Anal ; 166: 30-39, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30599279

RESUMO

Diabetic nephropathy (DN) is one of the leading causes of death in diabetes mellitus (DM). Early warning and therapy has significant clinical value for DN. This research sought to find biomarkers to predict the occurrence and development of DN and the intervention of Ginkgo biloba leaves extract (GBE) by quantifying fatty acids, amino acids, and nucleosides and nucleobases in rat plasma. Samples were respectively collected at the weekend of 5-10 weeks after diabetic rats induced by streptozotocin were defined. Plasma fasting blood-glucose, kidney index, blood urea nitrogen, creatinine, urine albumin excretion and ultrastructural morphology of kidney were measured or observed. Fatty acids, amino acids and nucleosides and nucleobases in rat plasma were analyzed by gas chromatography or liquid phase chromatography and mass spectrometry, respectively. From the biochemical index and morphological change of kidney, the rats from the 5th to 7th week were in the stage of DM while from the begin of 8th week the rats were suggested in the early stage of DN. The results of quantitative metabolomics showed that 16 differential metabolites were related to the progression of DN, and oleic acid, glutamate and guanosine might be the potential biomarkers of kidney injury. 14 differential metabolites were related to GBE against the progression of DN, while oleic acid and glutamate might be the potential biomarkers of GBE against kidney injury. Those findings potentially promote the understanding of the pathogenic progression of DN and reveal the therapeutic mechanism of GBE against DN.


Assuntos
Aminoácidos/sangue , Nefropatias Diabéticas/sangue , Ácidos Graxos/sangue , Metabolômica , Nucleosídeos/sangue , Extratos Vegetais/uso terapêutico , Albuminúria , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/tratamento farmacológico , Ginkgo biloba , Rim/patologia , Rim/ultraestrutura , Masculino , Ratos
12.
Dalton Trans ; 46(39): 13482-13491, 2017 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-28951916

RESUMO

Organometallic iridium complexes have emerged as potent anticancer agents in recent years. In this work, three cyclometalated iridium(iii) complexes Ir1-Ir3 containing monodentate five-membered heterocyclic ligands have been synthesized and characterized. Upon visible light (425 nm) irradiation, the five-membered heterocyclic ligands will dissociate from the metal centre. Moreover, Ir1-Ir3 can also act as effective singlet oxygen photosensitizers. Thus, Ir1-Ir3 can exert their light-mediated activation of anticancer effects by dual modes including ligand exchange reactions and generation of singlet oxygen (1O2) upon visible light irradiation. Notably, Ir1 displays a high phototoxicity index of 61.7 against human cancer cells. Further studies show that light-mediated anticancer properties exerted by Ir1-Ir3 occur through reactive oxygen species (ROS) generation, caspase activation, and eventually apoptosis induction. Our study demonstrates that these complexes can act as novel dual-mode light-mediated anticancer agents.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Compostos Heterocíclicos/química , Irídio/química , Fármacos Fotossensibilizantes/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Luz , Microscopia Confocal , Conformação Molecular , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-26113453

RESUMO

The mesangial cell (MC) cultured with high glucose has been used to observe the protective effect of Ginkgo biloba extract (GBE) against diabetic nephropathy (DN), but the compounds interacting with cell are still unknown, which may be potential bioactive components. Based on this, the determination of GBE in MC lysates was proposed by high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) in this study. The MC was cultured with normal or high glucose with GBE for 4, 8, 12, 16, 24 and 48h. The harvested cell was extracted with 40% acetic acid in water and further analyzed by LC-MS/MS. All the validation data including linearity, intra-day and inter-day precision, limit of detection and quantification, matrix effect, and stability were within the required limits. The validated method was successfully applied to quantify 11 compounds of GBE in cell lysates. The results showed that high glucose prolonged the peak time of all observed 11 compounds and peak concentrations of bilobalide, ginkgolide C, ginkgolide B, quercetin, luteolin, kaempferol, isorhamnetin and genkwanin in cell lysates, which hinted that these compounds may be the potential bioactive components of GBE with preventive effect against DN.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ginkgo biloba/química , Células Mesangiais/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/metabolismo , Espectrometria de Massas em Tandem/métodos , Técnicas de Cultura de Células , Nefropatias Diabéticas , Glucose/metabolismo , Humanos , Reprodutibilidade dos Testes
14.
Biomed Chromatogr ; 29(12): 1819-25, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26018907

RESUMO

A novel UPLC-DAD method was developed and validated for the simultaneous determination of baicalin (baicalein-7-glucuronide, BG), oroxylin A-7-O-glucuronide (OAG) and wogonoside (WG) in rat plasma using rutin as the internal standard. Plasma samples were precipitated using acetonitrile containing 0.1% formic acid. Separation was performed on an Agilent Eclipse Plus C18 column (2.1 × 50 mm, 1.8 µm) using gradient acetonitrile and 0.2% formic acid water solution as mobile phase. The flow-rate was set at 0.4 mL/min and the eluate was detected at 275 nm. The method was linear over the ranges of 0.075-17.50, 0.050-12.60 and 0.056-14.10 µg/mL for BG, OAG and WG, respectively. The intra- and inter-day precisions were respectively <4.8% and 6.4%. All of the limits of detection of three analytes in rat plasma were 0.01 µg/mL, whereas the limits of quantification were, respectively, 0.035, 0.025 and, 0.025 µg/mL. This assay has been successfully applied to pharmacokinetics of BG, OAG and WG in rats after oral administration of Yinhuang granule (YHG) and comparative pharmacokinetics of BG in rats following oral administration of the pure BG, Radix Scutellariae (RS) or YHG. We speculate that some co-existing ingredients in RS or YHG may increase the absorption and elimination of BG in rat. This work may be helpful for the quality control of Yinhuang granule.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/sangue , Flavonoides/farmacocinética , Administração Oral , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Flavonoides/química , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Scutellaria baicalensis
15.
Anal Bioanal Chem ; 407(14): 4143-53, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25855151

RESUMO

The quantitative analysis of taurine and edaravone in biological sample is critical in pharmaceutical studies. Although each of them can be individually analyzed by different approaches, concurrent quantification is still a highly challenging task with respect to their great polarity variation and the complex composition of tissue sample. In the present study, to simultaneously determine taurine and edaravone in rat tissue, the sample preparation and chromatographic separation conditions were evaluated and discussed in detail. As for the sample preparation, four kinds of solvent and the volume ratio of the optimal solvent to biological sample were both tested and evaluated based on the chromatographic profile, extraction recovery, and matrix effect (ME). The chromatographic separation was performed in a reverse phase (RP) and two hydrophilic interaction liquid chromatography (HILIC) modes, and the corresponding separation efficiencies were assessed using chromatographic parameters like half-width (W 1/2 ), tailing factor (f t), theoretical plates number (N), and ME. Furthermore, adopted composition of two mobile phase systems and the concentrations of the additives in the optimum buffer system were also investigated on an Atlantis HILIC silica column according to the resultant chromatographic profiles and peak areas of the analytes. The optimal results were obtained when the biological samples were deproteined by 4-fold volume of methanol/acetonitrile (1:3, v/v) and separated on a HILIC column with a gradient elution of acetonitrile/water containing 0.2 % formic acid and 10 mM ammonium formate. The proposed approach was validated and successfully applied to the parallel determination of the tissue distribution of edaravone and taurine in rat tissues.


Assuntos
Antipirina/análogos & derivados , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Taurina/química , Animais , Antipirina/química , Química Encefálica , Edaravone , Rim/química , Fígado/química , Miocárdio/química , Ratos , Baço/química
16.
Biomed Chromatogr ; 28(9): 1173-82, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24706508

RESUMO

Three liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the simultaneous or independent determination of taurine and edaravone in rat plasma using 3-methyl-1-p-tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Chromatographic separations were achieved on an Agilent Zorbax SB-Aq (100 × 2.1 mm, 3.5 µm) column. Gradient 0.03% formic acid-methanol, isocratic 0.1% formic acid-methanol (90:10) and 0.02% formic acid-methanol (40:60) were respectively selected as the mobile phase for the simultaneous determination of two analytes, taurine or edaravone alone. The MS acquisition was performed in multiple reaction monitoring mode with a positive and negative electrospray ionization source. The mass transitions monitored were m/z [M + H](+) 175.1 → 133.0 and [M + H](+) 189.2 → 147.0 for edaravone and its IS, m/z [M - H](-) 124.1 → 80.0 and [M - H](-) 172.0 → 80.0 for taurine and its IS, respectively. The validated methods were successfully applied to study the pharmacokinetic interaction of taurine and edaravone in rats after independent intravenous administration and co-administration with a single dose. Our collective results showed that there were no significant alterations on the main pharmacokinetic parameters (area under concentration-time curve, mean residence time, half-life and clearance) of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible.


Assuntos
Antipirina/análogos & derivados , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Taurina/sangue , Administração Intravenosa , Animais , Antipirina/administração & dosagem , Antipirina/sangue , Antipirina/química , Antipirina/farmacocinética , Interações Medicamentosas , Edaravone , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Taurina/administração & dosagem , Taurina/química , Taurina/farmacocinética
17.
J Sep Sci ; 36(24): 3837-44, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24133013

RESUMO

An LC-MS/MS method was developed and validated for the simultaneous quantification of edaravone and taurine in beagle plasma. The plasma sample was deproteinized using acetonitrile containing formic acid. Chromatographic separations were achieved on an Agilent Zorbax SB-Aq (100 × 2.1 mm, 3.5 µm) column, with a gradient of water (containing 0.03% formic acid) and methanol as the mobile phase at a flow rate of 0.3 mL/min. The analyte detection was carried out in multiple reaction monitoring mode and the optimized precursor-to-product transitions of m/z [M+H](+) 175.1 → 133.0 (edaravone), m/z [M+H](+) 189.1 → 147.0 (3-methyl-1-p-tolyl-5-pyrazolone, internal standard, IS), m/z [M-H](-) 124.1→80.0 (taurine), and m/z [M-H](-) 172.0 → 80.0 (sulfanilic acid, IS) were employed to quantify edaravone, taurine, and their corresponding ISs, respectively. The LOD and the lower LOQ were 0.01 and 0.05 µg/mL for edaravone and 0.66 and 2 µg/mL for taurine, respectively. The calibration curves of these two analytes demonstrated good linearity (r > 0.99). All the validation data including the specificity, precision, recovery, and stability conformed to the acceptable requirements. This validated method has successfully been applied in the pharmacokinetic study of edaravone and taurine mixture in beagle dogs.


Assuntos
Antipirina/análogos & derivados , Taurina/sangue , Animais , Antipirina/sangue , Antipirina/química , Cromatografia Líquida de Alta Pressão , Cães , Edaravone , Espectrometria de Massas em Tandem , Taurina/química
18.
Eur J Med Chem ; 63: 269-78, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23501112

RESUMO

IκB kinase ß (IKKß), an attractive anti-inflammation and anti-cancer target, plays a crucial role in the activation of NF-κB signalling pathway. To identify novel IKKß inhibitors, we combined structure-based and ligand-based methods based on the co-crystal structure of IKKß. According to the chemical similarity, 162 reported IKKß inhibitors were divided into five classes. For each class, a 3D pharmacophore model was established based on the binding conformations of the compounds. The validated models were further used in virtual screening. Twelve drugable compounds were retained for biological test, resulting in two novel inhibitors with IC50 values lower than 10 µM. Compared to other models, our method considers the crystal structure of IKKß for the first time.


Assuntos
Quinase I-kappa B/química , Conformação Molecular , Inibidores de Proteínas Quinases/química , Estrutura Terciária de Proteína , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Quinase I-kappa B/antagonistas & inibidores , Quinase I-kappa B/metabolismo , Ligantes , Modelos Moleculares , Estrutura Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Relação Estrutura-Atividade
19.
Talanta ; 85(2): 885-90, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21726714

RESUMO

A novel method combining high performance liquid chromatography (HPLC) fingerprint and simultaneous quantitative analysis of multiple active components was developed and validated for quality evaluation of one type of traditional Chinese medicine preparations: Shuang-huang-lian (SHL) oral liquid formulation. For fingerprint analysis, 45 peaks were selected as the common peaks to evaluate the similarities among several different SHL oral liquid preparations collected from manufacturers. Additionally, simultaneous quantification of eleven markers, including chlorogenic acid, caffeic acid, rutin, forsythiaside, scutellarin, baicalin, forsythin, luteoloside, apigenin, baicalein and wogonin, was performed. Statistical analysis of the obtained data demonstrated that our method has achieved desired linearity, precision and accuracy. Finally, concentrations of these eleven markers in SHL oral liquid prepared by different manufacturers in China were determined. These results demonstrated that the combination of HPLC chromatographic fingerprint and simultaneous quantification of multi-ingredients offers an efficient and reliable approach for quality evaluation of SHL oral liquid preparations.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa/normas , Administração Oral , Composição de Medicamentos/normas , Medicamentos de Ervas Chinesas/administração & dosagem , Limite de Detecção , Modelos Lineares , Controle de Qualidade , Reprodutibilidade dos Testes
20.
Artigo em Chinês | MEDLINE | ID: mdl-12884613

RESUMO

OBJECTIVE: To sub-clone and express the gene encoding Schistosoma japonicum calcium-binding protein (SjE16) and study its immunological response. METHODS: The specific primers were designed according to the expressed sequence tags (ESTs) sequence, which was used for amplification of the encoding sequence from the cDNA clone containing SjE16. The gene was subcloned into pGEX4T-1 plasmid and expressed. The rSjE16 was tested for its immunological response by ELISA. RESULTS: The gene encoding Schistosoma japonicum SjE16 was cloned and expressed successfully. The immunogenicity and diagnostic potential of rSjE16 were investigated. It was demonstrated by immunoassay in rabbits that the specificity and sensitivity of the test were 94.1% (16/17) and 88.2% (15/17), respectively, and the level of antibody titer of the untreated group reached a peak at 9-11 wk post infection and maintained high at least for 21 wk post infection, while the antibody level in the treated group rapidly decreased to pre-infection level in 11 wk after treatment. In human, the specificity of the test was 98.3% (57/58); the sensitivity of acute and chronic patient serum assay was 85.5% (53/62) and 70.2% (40/57), respectively. CONCLUSION: The recombinant protein of SjE16 (rSjE16) was acquired. It can be recognized by the sera from schistosomiasis patients, and the level of antibodies decreased quickly after treatment in experimental rabbits, which implicates the potential value for the evaluation of chemotherapy and detection of active infection.


Assuntos
Proteínas de Ligação ao Cálcio/imunologia , Proteínas Recombinantes de Fusão/imunologia , Schistosoma japonicum/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Proteínas de Ligação ao Cálcio/biossíntese , Proteínas de Ligação ao Cálcio/genética , Ensaio de Imunoadsorção Enzimática , Etiquetas de Sequências Expressas , Testes Imunológicos , Proteínas Recombinantes de Fusão/biossíntese , Schistosoma japonicum/genética , Esquistossomose Japônica/diagnóstico , Sensibilidade e Especificidade
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