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1.
Opt Lett ; 48(9): 2484-2487, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37126305

RESUMO

The characteristics of two noninteger cylindrical vector vortex beams (NCVVBs) propagating through a radial gradient-index (GRIN) fiber are analyzed on the basis of the generalized Huygens-Fresnel principle. The NCVVBs exhibit periodic and stable transmission characteristics in the radial GRIN fiber. Polarization changes, the presence of spin angular momentum (SAM), and changes in the orbital angular momentum (OAM) of the NCVVBs are observed at the focal plane of the radial GRIN fiber. Spin-orbit interactions of NCVVBs are verified in the radial GRIN fiber for the first time, to the best of our knowledge.

2.
Opt Express ; 31(2): 1832-1843, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36785209

RESUMO

Spin-orbit interactions (SOIs) of circularly polarized beam and circularly polarized vortex beam during paraxial propagation in a radial gradient-index (GRIN) fiber are analyzed using the generalized Huygens-Fresnel principle and the GRIN fiber's ABCD matrix. SAM is only associated with polarized light helicity and OAM is only associated with topological charge m. SAM and OAM do not crosstalk or convert between each other; SOIs did not occur at the GRIN fiber's focal plane. SOIs of partially coherent circularly polarized beam and partially coherent circularly polarized vortex beam in the GRIN fiber are also studied and show the same characteristics as the perfectly polarized beam.

3.
J Colloid Interface Sci ; 633: 374-382, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36459942

RESUMO

Rational design and facile preparation of high-performance carbon-based eletrocatalysts for both oxygen reduction and evolution reactions (ORR and OER) is crucial for practical applications of rechargeable zinc-air batteries. Inspired by the fact that the metallic Co catalysis on the formation of carbon nanotubes (CNTs), this work develops a facial compression-pyrolysis route to synthesize a mesoporous waffle-like N-doped carbon framework with embedded Co nanoparticles (Co@pNC) using a Co metal-organic framework and melamine as precursors. The unique porous waffle-like carbon framework is built up of interwoven N-doped CNTs and graphene nanosheets, which offers abundant catalytic-active sites and rapid diffusion channels for intermediates and electrolyte. The optimized Co@pNC shows excellent bifunctional ORR/OER electrocatalytic activity in alkaline media with a half-wave potential (E1/2) of 0.85 V for ORR and a small potential gap of 0.70 V between ORR E1/2 and OER potential at 10 mA cm-2. Its assembled battery exhibits a peak power density up to 150.3 mW cm-2, an energy density of 928 Wh kgZn-1 and superb rate capability. It highlights a facile component and architecture strategy to design high-performance carbon-based eletrocatalysts.

4.
Opt Express ; 30(10): 16432-16441, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-36221486

RESUMO

The characteristics of the cylindrical vector beam (CVB) and the cylindrical vector vortex beam (CVVB) in a radial gradient-index (GRIN) fiber are analyzed on the basis of the generalized Huygens-Fresnel principle. The CVB and CVVB exhibit periodic and stable transmission characteristics in the radial GRIN fiber. In the beam with a vortex phase (CVVB), the polarization changes and the spin angular momentum (SAM) is detected at the focal plane of the radial GRIN fiber. A spin-orbit periodic conversion is observed in the radial GRIN fibers. Finally, the SAM expression of partially coherent light is deduced and verified via a simulation.

5.
Appl Opt ; 61(1): 115-119, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35200802

RESUMO

Using the previously proposed spin-resolved near-field scanning optical microscopy (NSOM) technique, we mapped the spin angular momentum (SAM) axial component (Sz) distributions of tightly focused linearly and circularly polarized vortex beams. The system's effectiveness was confirmed in our previous article by mapping various tightly focused cylindrical vector vortex beams. The SAM of different focused vortex light fields is essential in the research of near-field spin optics and topological photonics. The SAM distributions of different orders of linearly and circularly polarized vortex beams were mapped by separating their right spin (IRCP) and left spin component (ILCP) using the relationship Sz∝IRCP-ILCP.

6.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(5): 580-584, 2021 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-34628777

RESUMO

The panoramic perception of medical equipment operation and maintenance status is the basic guarantee for the implementation of smart medical care, the machine learning algorithm-based autonomous perception and active early warning model of medical equipment operation and maintenance status is proposed. Introduce deep learning multi-dimensional perception of medical equipment multi-source heterogeneous fault data training sample characteristics to realize autonomous perception of medical equipment operation and maintenance status, introduce reinforcement learning to realize autonomous decision-making of test sample fault characteristics, and build the active early warning mechanism for medical equipment faults. Taking the equipment department of hospital as the carrier of model effectiveness verification, the effectiveness simulation of the model was carried out, the results show that the model has the advantages of comprehensive fault information perception, strong compatibility of medical equipment, high efficiency of active early warning.


Assuntos
Algoritmos , Aprendizado de Máquina , Simulação por Computador , Autoimagem , Equipamentos Cirúrgicos
7.
Opt Express ; 28(10): 14831-14838, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32403517

RESUMO

Near-field scanning optical microscopy (NSOM) is a powerful tool for study of the nanoscale information of objects by measuring their near-field electric field distributions. The near-field probe, which determines NSOM system performance, can be either a scattering-type or an aperture-type. Both types have strengths and weaknesses. Here we propose and study a surface plasmon-coupled type nano-probe, which works as a hybrid scheme and could potentially combine the advantages of the two NSOM probe types. The key element of the proposed probe is a nanoparticle-on-film structure designed on a tapered fiber tip. On the one hand, the probe can yield the signals scattered in the near field by a nanoparticle with a scattering mechanism; on the other hand, the scattered signals can be transmitted by the metal film and coupled into the fiber via surface plasmon coupled emission, thus providing a collection mode similar to an aperture-type NSOM. This will lead to signal enhancement, while greatly suppressing background noise. This surface plasmon-coupled nano-probe thus has great potential for near-field optical microscopy applications.

8.
Food Chem ; 240: 239-244, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28946267

RESUMO

Ginger, the rhizome of Zingiber officinale Roscoe, is a popular spice used in the food, beverage and confectionary industries. In this study, we report an untargeted UPLC-Q/TOF-MS-based metabolomics approach for comprehensively discriminating between ginger from two geographical locations, Ghana in West Africa and China. Forty batches of fresh ginger from both countries were discriminated using principal component analysis and orthogonal partial least squares discrimination analysis. Sixteen differential metabolites were identified between the gingers from the two geographical locations, six of which were identified as the marker compounds responsible for the discrimination. Our study highlights the essence and predictive power of metabolomics in detecting minute differences in same varieties of plants/plant samples based on the levels and composition of their metabolites.


Assuntos
Metabolômica , Zingiber officinale , África Ocidental , China , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas
9.
Cancer Biol Ther ; 18(3): 166-176, 2017 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-28368741

RESUMO

Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related deaths with 750,000 newly diagnosed cases each year. Surgery, radiotherapy, and chemotherapy constitute the main treatment modalities for HCC, but liver cirrhosis and damage often occur. Molecular targeted drugs have been recently developed to treat HCC. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) autocrine signaling is closely related to the growth, progression, and metastasis of HCC, making the VEGF/VEGFR axis an ideal target for the development of molecular targeted agents. Here, we report the effects of the novel anti-VEGF humanized monoclonal antibody BD0801 on the growth of HCC cells in vitro and in vivo as well as the underlying mechanisms. BD0801 significantly inhibited the proliferation of HepG2, SMMC-7721, and Bel7402 cells in vitro, accompanied with an induction of apoptosis and cell cycle arrest at the G1 phase. BD0801 potently suppressed AKT, Erk1/2, and retinoblastoma (Rb) phosphorylation, while increasing p21 and decreasing cyclin D1 protein levels. BD0801 significantly inhibited growth in mouse tumor xenografts and induced cell apoptosis of HepG2 and SMMC-7721 tumor xenografts. Furthermore, BD0801 effectively reduced the vascular density and tumor tissue microvessel density (MVD). Similarly, BD0801 decreased AKT, Erk1/2, and Rb phosphorylation and cyclin D1 expression whereas it increased p21 protein expression in mouse HCC tumor xenografts. Importantly, BD0801 showed a better effect than Bevacizumab (Bev) on the inhibition of cell growth and induction of apoptosis in HCC cells in vitro and in vivo. These findings suggest that BD0801 is a potent anti-VEGF monoclonal antibody for the treatment of HCC.


Assuntos
Anticorpos Monoclonais/farmacologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Fator A de Crescimento do Endotélio Vascular/imunologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Anticorpos Monoclonais/imunologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Appl Opt ; 55(5): 974-8, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26906361

RESUMO

An all-fiber reflecting fluorescent temperature probe is proposed based on the simplified hollow-core photonic crystal fiber (SHC-PCF) filled with an aqueous CdSe/ZnS quantum dot solution. SHC-PCF is an excellent PCF used to fill liquid materials, which has low loss transmission bands in the visible wavelength range and enlarged core sizes. Both end faces of the SHC-PCF were spliced with multimode fiber after filling in order to generate a more stable and robust waveguide structure. The obtained temperature sensitivity dependence of the emission wavelength and the self-referenced intensity are 126.23 pm/°C and -0.007/°C in the temperature range of -10°C-120°C, respectively.


Assuntos
Tecnologia de Fibra Óptica/métodos , Fibras Ópticas , Fótons , Pontos Quânticos/química , Temperatura , Compostos de Cádmio/química , Luminescência , Compostos de Selênio/química , Soluções , Espectrometria de Fluorescência , Sulfetos/química , Compostos de Zinco/química
11.
Oncol Lett ; 9(6): 2694-2700, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26137130

RESUMO

Endostar, a modified recombinant human endostatin, inhibits the growth of a variety of tumors by suppressing neovascularization. Vascular endothelial growth factor (VEGF) has an important role in malignant ascites formation. In order to determine whether Endostar can suppress the formation of ascites and prolong survival times, mouse models of malignant ascites were established using S180 and H22 tumor cells. The experimental mice were randomly divided into four groups: The three treatment groups received different doses of Endostar (4, 8 and 16 mg/kg), and the control group received 0.9% w/v NaCl. The volume of ascites, and the tumor cell, red blood cell (RBC), VEGF protein and mRNA content of the ascites was measured alongside the peritoneal permeability and the mouse survival time. In vitro analysis of cultured Endostar-treated S180 and H22 cells was also performed in order to examine cellular proliferation and the level of VEGF secreted protein and mRNA. The results revealed that Endostar suppressed the ascites volume, decreased the level of tumor cells, RBCs and VEGF in the ascites fluid, and lowered the permeability of the peritoneum. The tumor cells collected from the ascites in the Endostar-treated mice demonstrated a decrease in the expression of VEGF mRNA. The survival rates of the 8 and 16 mg/kg Endostar-treated mice were longer than those of the controls. The in vitro experiments revealed a significant inhibition of VEGF protein secretion and VEGF mRNA by Endostar, but no effect on cellular proliferation. In conclusion, Endostar lowers ascites production by downregulating VEGF expression, and may therefore be effective for the treatment of malignant ascites.

12.
Gastroenterol Res Pract ; 2015: 957574, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25983751

RESUMO

To investigate the effect of endostar on specific angiogenesis induced by human hepatocellular carcinoma, this research systematically elucidated the inhibitory effect on HepG2-induced angiogenesis by endostar from 50 ng/mL to 50000 ng/mL. We employed fluorescence quantitative Boyden chamber analysis, wound-healing assay, flow cytometry examination using a coculture system, quantitative analysis of tube formation, and in vivo Matrigel plug assay induced by HCC conditioned media (HCM) and HepG2 compared with normal hepatocyte conditioned media (NCM) and L02. Then, we found that endostar as a tumor angiogenesis inhibitor could potently inhibit human umbilical vein endothelial cell (HUVEC) migration in response to HCM after four- to six-hour action, inhibit HCM-induced HUVEC migration to the lesion part in a dose-dependent manner between 50 ng/mL and 5000 ng/mL at 24 hours, and reduce HUVEC proliferation in a dose-dependent fashion. Endostar inhibited HepG2-induced tube formation of HUVECs which peaked at 50 ng/mL. In vivo Matrigel plug formation was also significantly reduced by endostar in HepG2 inducing system rather than in L02 inducing system. It could be concluded that, at cell level, endostar inhibited the angiogenesis-related biological behaviors of HUVEC in response to HCC, including migration, adhesion proliferation, and tube formation. At animal level, endostar inhibited the angiogenesis in response to HCC in Matrigel matrix.

13.
Vaccine ; 33(35): 4247-54, 2015 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-25858855

RESUMO

Hepatitis B virus infection is a non-cytopathic hepatotropic virus which can lead to chronic liver disease and hepatocellular carcinoma. Traditional therapies fail to provide sustained control of viral replication and liver damage in most patients. As an alternative strategy, immunotherapeutic approaches have shown promising efficacy in the treatment of chronic hepatitis B patients. Here, we investigated the efficacy of a novel therapeutic vaccine formulation consisting of two HBV antigens, HBsAg and HBcAg, and CpG adjuvant. This vaccine formulation elicits forceful humoral responses directed against HBsAg/HBcAg, and promotes a Th1/Th2 balance response against HBsAg and a Th1-biased response against HBcAg in both C57BL/6 and HBV transgenic mice. Vigorous cellular immune response was also detected in HBV transgenic mice, for a significantly higher number of HBs/HBc-specific IFN-γ secreting CD4+ and CD8+ T cells was generated. Moreover, vaccinated mice elicited significantly intense in vivo CTL attack, reduced serum HBsAg level without causing liver damage in HBV transgenic mice. In summary, this study demonstrates a novel therapeutic vaccine with the potential to elicit vigorous humoral and cellular response, overcoming tolerance in HBV transgenic mice.


Assuntos
Adjuvantes Imunológicos , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Vacinas contra Hepatite B/uso terapêutico , Hepatite B Crônica/terapia , Oligodesoxirribonucleotídeos/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/química , Hepatite B Crônica/imunologia , Tolerância Imunológica , Imunidade Celular , Imunidade Humoral , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Oligodesoxirribonucleotídeos/uso terapêutico , Equilíbrio Th1-Th2
14.
Exp Ther Med ; 4(2): 277-284, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23139716

RESUMO

To explore an effective combination therapy for malignant ascites, the therapeutic value of the combination of Endostar, a modified recombinant human endostatin, and ß-elemene, an active component of a traditional Chinese herb, in an H22 mouse malignant ascites model was investigated. The optimal dose combination of Endostar and ß-elemene was determined by evaluating the inhibition of ascites volume and increase in the survival rate of the mice. Other therapeutic effects and the underlying mechanisms were investigated under the optimal dose combination (8 mg/kg Endostar plus 100 mg/kg ß-elemene). The mice were randomly divided into four treatment groups and received intraperitoneal injection once a day for eight days: control (0.9% normal saline), Endostar (8 mg/kg), ß-elemene (100 mg/kg) or optimal dose combination (8 mg/kg Endostar plus 100 mg/kg ß-elemene), respectively. The results of this study revealed that the combination therapy had significant synergistic effects on the inhibition of ascites formation and a deceased number of tumor cells and protein levels in ascites compared with the results of treatment with a single agent. A decreased peritoneal microvascular permeability and reduction in VEGF, MMP-2 and hypoxia inducible factor 1α (HIF1α) was noted in the combination group, when compared with single agent treatment. These studies found that in the ascitic tumor cells, the protein levels of VEGF and MMP-2, as well as levels of VEGF mRNA, were significantly inhibited by the combination therapy. The potentiating effects of the combination of Endostar with ß-elemene suggest that this novel therapy may yield an effective therapy for the treatment of malignant ascites.

15.
J Ind Microbiol Biotechnol ; 39(3): 471-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21997275

RESUMO

CD137 ligand (CD137L) is a member of the tumor-necrosis factor superfamily that binds CD137 to provide positive co-stimulatory signals for T cells activation. Co-stimulation through CD137/CD137L has become one of the promising approaches for cancer therapy. Previous reports have shown that CD137L expressed in Escherichia coli resulted in inclusion bodies or low yield. In this study, the effects of five different chaperone teams on the soluble expression of recombinant human CD137L protein were explored and analyzed. The poor expression of CD137L in the cytoplasm of E. coli was improved significantly by co-expression of chaperone GroES-GroEL-Tf. After dual induction and affinity chromatography, purified recombinant CD137L was obtained at a yield of 3 mg protein per liter with purity greater than 98% from original undetectable level. Additionally, the purified recombinant CD137L could bind CD137-positive cells in a dose-dependent manner, markedly promote the growth of activated mice T cells, and elevate the release of IL-2. The present work provides an effective system for soluble expression of functional human co-stimulatory molecule CD137L, which will facilitate the clinical developments of recombinant protein drugs.


Assuntos
Ligante 4-1BB/metabolismo , Escherichia coli/metabolismo , Animais , Bioengenharia , Biotecnologia , Escherichia coli/genética , Fermentação , Humanos , Ativação Linfocitária/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Chaperonas Moleculares/metabolismo , Ligação Proteica/fisiologia , Proteínas Recombinantes/metabolismo
16.
Cancer Immunol Immunother ; 61(4): 489-95, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21968735

RESUMO

Co-stimulatory molecules can be efficiently produced as a recombinant protein in E. coli with a large range of applications in the fields of immunotherapy. However, whether, different fusions that would affect their functions have rarely been analyzed. To explore the effects of different fusions and linkers on the molecular conformation and activity of CD137 ligand (CD137L), a recombinant human CD137L protein (rhCD137L) library, which consists of the entire extracellular domain of human CD137L fused to N- or C-terminal His-tag through different linkers, was constructed and all rhCD137Ls were, respectively, expressed in E. coli BL21 (DE3) strain carrying a chaperone plasmid pG-Tf2. After purification of the soluble rhCD137Ls, the recombinant fusion proteins could markedly promote the growth of activated T cells, but their effects on cytokine productions were different from each other. The present work indicated that, although all rhCD137Ls have desired biological activity, different fusions and linkers did affect their structures and functions. Consequently, rational design of a library is a necessary and feasible approach for fusion proteins in order to obtain a satisfactory drug candidate for further development.


Assuntos
Ligante 4-1BB/química , Ligante 4-1BB/uso terapêutico , Imunoterapia , Neoplasias/terapia , Proteínas Recombinantes de Fusão/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Técnicas de Química Combinatória , Citocinas/genética , Citocinas/imunologia , Descoberta de Drogas , Escherichia coli/genética , Engenharia Genética , Humanos , Ativação Linfocitária/efeitos dos fármacos , Neoplasias/imunologia , Conformação Proteica , Proteínas Recombinantes de Fusão/uso terapêutico , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
17.
Int J Pharm ; 397(1-2): 136-43, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20655370

RESUMO

The incomplete release of Endostar from PLGA microspheres was observed in our previous study. In the present study, we focused on the effect of medium-chain triglycerides (MCT) on the in vitro/in vivo release behavior of Endostar encapsulated PLGA microspheres, which were prepared by a water-in-oil-in-water (W/O/W) double-emulsion method with or without MCT. The in vitro accumulated release of Endostar from microspheres co-encapsulated with 30% MCT was found to be 79.04% after a 30-day incubation period in PBS (pH 7.4) at 37 degrees C. However, the accumulated release of Endostar from MCT-free microspheres was found to be only 32.22%. Pouches containing Endostar encapsulated PLGA microspheres were implanted subcutaneously in rats. The effect of MCT on the in vivo release showed a similar trend to the in vitro release. After 30 days, only 9.87% of the total encapsulated Endostar was retained in microspheres co-encapsulated with 30% MCT, while 42.25% of Endostar was retained in MCT-free microspheres. The co-encapsulation of MCT provided the microspheres with a porous surface, which significantly improved the in vitro/in vivo release of Endostar from PLGA microspheres. In addition, in vitro experiments showed that MCT co-encapsulated PLGA microspheres had more inter-connected pores, faster degradation of PLGA, and faster swelling of microspheres, which helped to explain the mechanism of the effect of MCT on improving the release of Endostar from PLGA microspheres.


Assuntos
Inibidores da Angiogênese/farmacocinética , Endostatinas/farmacocinética , Ácido Láctico , Ácido Poliglicólico , Triglicerídeos , Animais , Química Farmacêutica , Portadores de Fármacos , Composição de Medicamentos , Estabilidade de Medicamentos , Emulsões , Masculino , Microesferas , Microtecnologia , Peso Molecular , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(7): 1509-13, 2010 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-20650753

RESUMO

OBJECTIVE: To investigate the effect of endostar in controlling ascites tumor formation in mice. METHODS: Mouse models bearing ascites tumors were established via intraperitoneal injection of H22 and S180 cell lines. Eighty-eight ICR mice were randomly assigned into 4 groups, namely the control group (0.9% normal saline) and 3 endostar groups with 8 mg/kg endostar administration daily, every other day or every two days. The peritoneal membrane permeability of the mice was assessed using Evan blue staining. The body weight curve of mice was drawn, and the cumulative ascites volume and number of red cells and tumor cells in the malignant ascites were determined. The survival of the mice was evaluated to assess the therapeutic effect of endostar. RESULTS: Compared with the control group, the mice receiving daily endostar injection showed obviously lower ascites accumulation and peritoneal capillary permeability (P<0.05) with reduced count of ascites tumor cells and red cells and tumor burden of the abdominal cavity. The mice with daily endostar injection also showed longer survival than the control group. CONCLUSIONS: Continuous intraperitoneal injection can be the optimal means for endostar administration for treatment of malignant ascites.


Assuntos
Carcinoma de Ehrlich/irrigação sanguínea , Endostatinas/administração & dosagem , Endostatinas/farmacologia , Animais , Linhagem Celular Tumoral , Endostatinas/uso terapêutico , Feminino , Humanos , Camundongos , Camundongos Endogâmicos ICR , Neovascularização Patológica , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico
19.
Int J Biol Macromol ; 46(3): 331-6, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20122957

RESUMO

In this study, we investigated the PEG attachment site of mono-PEGylated Endostar, a modified recombinant human endostatin approved in China for lung cancer. N-terminal site-directed mono-PEGylation of Endostar was accomplished using mPEG-propionaldehyde derivatives (Mw=20 kDa) under slightly acidic pH conditions (pH 5.5). One-step cation exchange chromatography was used to purify the mono-PEGylated Endostar. Following tryptic digestion, the peptide fragment containing PEG was separated by SDS-PAGE. Barium iodide staining and Western blotting were used to detect the PEG moiety and the N-terminus of Endostar, respectively. The peptide fragment stained by barium iodide showed a positive response to anti-(His) 6 mAb, demonstrating that PEG was located at the N-terminus of Endostar. LC/MS was applied to verify the occurrence of mono-PEGylation at the N-terminus of Endostar.


Assuntos
Endostatinas/análise , Polietilenoglicóis/análise , Sequência de Aminoácidos , Western Blotting , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Cromatografia de Fase Reversa , Eletroforese em Gel de Poliacrilamida , Endostatinas/química , Endostatinas/isolamento & purificação , Humanos , Dados de Sequência Molecular , Peptídeos/química , Polietilenoglicóis/química , Polietilenoglicóis/isolamento & purificação , Proteínas Recombinantes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Tripsina/metabolismo
20.
Eur J Med Chem ; 44(4): 1486-99, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18771818

RESUMO

Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed for a series of dipeptide boronate proteasome inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. A training set containing 46 molecules served to establish the models. The optimum CoMFA and CoMSIA models obtained for the training set were all statistically significant with cross-validated coefficients (q(2)) of 0.676 and 0.630 and conventional coefficients (r(2)) of 0.989 and 0.956, respectively. The predictive capacities of both models were successfully validated by calculating a test set of 13 molecules that were not included in the training set. The predicted correlation coefficients (r(2)(pred)) of CoMFA and CoMSIA are 0.963 and 0.919, respectively. The CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of beta5 subunit of 20S proteasome, which suggests that the 3D-QSAR models constructed in this paper can be used to guide the development of novel dipeptide boronate inhibitors of 20S proteasome.


Assuntos
Boro/química , Dipeptídeos/química , Dipeptídeos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Modelos Moleculares , Inibidores de Proteassoma , Relação Quantitativa Estrutura-Atividade , Simulação por Computador , Desenho de Fármacos , Ligantes , Conformação Molecular
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