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941.
Songyan Zheng Difei Qiu Monica Adams Jinjiang Li Rao V. Mantri Rajesh Gandhi 《AAPS PharmSciTech》2017,18(1):42-48
This study aimed in understanding the degradation behaviors of an IgG 1 subtype therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. The information obtained in this study can augment conventional, stability-based screening paradigms by providing the direction necessary for efficient experimental design. Differential scanning calorimetry (DSC) was used for studying conformational stability. Dynamic light scattering (DLS) was utilized to generate B 22*, a modified second virial coefficient for the character of protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC) were employed to separate degradation products. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for determining the molecular size and liquid chromatography mass spectrometry (LC-MS) were used for identifying the sequence of the separated fragments. The results showed that both pH and buffer species played the roles in controlling the degradation behaviors of mAb-A, but the pH was more significant. In particular, pH 4.5 induced additional thermal transition peaks occurring at a low temperature compared with pH 6.5. A continual temperature-stress study illustrated that the additional thermal transition peaks related to the least stable structure and a greater fragmentation. Although mAb-A showed the comparable conformational structures and an identical amount of aggregates at time zero between the different types of buffer species at pH 6.5, the aggregation formation rate showed a buffer species-dependent discrepancy over a temperature-stress period. It was found that the levels of aggregations associated with the magnitudes of protein-protein interaction forces. 相似文献
942.
Differential killing and radio-modifying effects of iodoacetate in mammalian normal and cancer cells
Usha?Yadav K.?B.?Anjaria Rajesha?Nairy K.?B.?Shirsath Utkarsha?N.?Desai Rajesh?K.?Chaurasia Nagesh?N.?BhatEmail author B.?K.?Sapra 《Radiation and environmental biophysics》2017,56(3):227-239
To explore possible applications of iodoacetate (IA), a glycolytic inhibitor, in cancer treatment, we screened its cytotoxicity and radioprotective/sensitizing efficacy in three different mammalian cell lines; A549 (human lung carcinoma), MCF7 (human mammary cancer), a non-cancerous CHO (Chinese hamster ovary) cells and human lymphocytes. Experiments were carried out using IA concentrations ranging from 0.01 to 2.5 µg/ml, with or without 60Coγ-radiation. In the outcomes, IA was found to exhibit higher toxicity in the cancer cells, whereas it was non-toxic/marginally toxic to the non-cancerous cells. Considerably higher glucose uptake in both cancer cells lines was observed indicating higher rates of glycolysis. IA significantly inhibited glycolysis as reflected by GAPDH activity inhibition. Radiomodifying effects of IA were found to be concentration dependent in both cancerous and non-cancerous cells. The response in non-cancerous was found to be biphasic: at lower concentrations, it offered significant radioprotection; however, the protection decreased with increasing concentration. Moreover, at the highest tested concentration, marginal radiosensitization was also observed (as indicated by clonogenic assay). In both cancer cells, IA offered significant amount of radiosensitization which was considerably high at higher concentrations. Further experiments were carried out to estimate the Dose Modification Factor (DMF) to quantify and compare relative radiosensitization by IA in cancer and normal cell lines. The DMF was calculated for three different concentrations of IA, 0.5, 1, and 1.5 µg/ml, and corresponding values were found to be 1.26, 1.43, and 1.89 for A549 cancer cells, whereas for normal CHO cells, it was 1.13, 1.13, and 1.24. In conclusion, differential killing and radiosensitizing effects of IA suggest that it may have potential use as a anticancer agent and radiosensitizer in cancer therapy. 相似文献
943.
944.
Krishan Kumar Gururaja Vulugundam Pradeep Kumar Jaiswal Bharti Rajesh Kumar Shyamlal Sandeep Chaudhary 《Bioorganic & medicinal chemistry letters》2017,27(18):4288-4293
This study reports the simultaneous delivery of EGFP siRNA and the chemotherapeutic drug, doxorubicin by means of the composition that results from the electrostatic interaction between positively charged siRNA-complexes of gold nanoparticles (AuNPs) capped with PEI, 25 kDa (P25-AuNPs) and negatively charged carboxymethyl cellulose formulated PLGA nanoparticles loaded with doxorubicin. The nanoparticles and their facile interaction were studied by means of dynamic light scattering (DLS), zeta potential, transmission electron microscopic (TEM) measurements. The flow cytometric and confocal microscopic analysis evidenced the simultaneous internalization of both labelled siRNA and doxorubin into around 55% of the HeLa cancer cell population. Fluorescence microscopic studies enabled the visual analysis of EGFP expressing HeLa cells which suggested that the composition mediated codelivery resulted in a substantial downregulation of EGFP expression and intracellular accumulation of doxorubicin. Interestingly, codelivery treatment resulted in an increased cellular delivery of doxorubicin when compared to PLGA-DOX alone treatment. On the other hand, the activity of siRNA complexes of PEI-AuNPs was completely retained even when they were part of composition. The results suggest that this formulation can serve as promising tool for delivery applications in combinatorial anticancer therapy. 相似文献
945.
Saikrishna Balabadra MeenaKumari Kotni Vijjulatha Manga Aparna Devi Allanki Rajesh Prasad Puran Singh Sijwali 《Bioorganic & medicinal chemistry》2017,25(1):221-232
Novel series of naphthyl bearing 1,2,3-triazoles (4a–t) were synthesized and evaluated for their in vitro antiplasmodial activity against pyrimethamine (Pyr)-sensitive and resistant strains of Plasmodium falciparum. The synthesized compounds were assessed for their cytotoxicity employing human embryonic kidney cell line (HEK-293), and none of them was found to be toxic. Among them 4j, 4k, 4l, 4m, 4n, 4t exhibited significant antiplasmodial activity in both strains, of which compounds 4m, 4n and 4t (~3.0-fold) displayed superior activity to Pyr against resistant strain. Pyr and selected compounds (4n, 4p and 4t) that repressed parasite development also inhibited PfDHFR activity of the soluble parasite extract, suggesting that anti-parasitic activity of these compounds is a result of inhibition of the parasite DHFR. In silico studies suggest that activity of these compounds might be enhanced due to π-π stacking. 相似文献
946.
Eun-A. Jo Rajesh Kumar Tewari Eun-Joo Hahn Kee-Yoeup Paek 《Plant biotechnology reports》2008,2(3):207-212
Plantlets of Alocasia amazonica regenerated under a photon flux density (PFD) of 15 or 30 μmol m−2 s−1 showed better growth and development than those grown under higher PFDs. While chlorophyll a and chlorophyll b decreased, the number of stomata increased with increasing PFD. Photoperiods also affected plantlet growth and stomatal development.
Highest growth was observed for the short photoperiod (8/16 h) and for equinoctial (12/12 h) light and dark periods. Very
few stomata developed in the leaves of plantlets grown under a short photoperiod (8/16 h) and the number of stomata increased
with increasing light period. In conclusion, both light intensity and photoperiod independently affect growth of A. amazonica and development of stomata, depending on the intensity and duration of light treatment. 相似文献
947.
This paper discusses the binding and release properties of hydrophobically modified hyperbranched polyglycerol-polyethylene glycol copolymers that were originally developed as human serum albumin (HSA) substitutes. Their unimolecular micellar nature in aqueous solution has been proven by size measurements and other spectroscopic methods. These polymers aggregate weakly in solution, but the aggregates are broken down by low shear forces or by encapsulating a hydrophobic ligand within the polymer. The small molecule binding properties of these polymers are compared with those of HSA. The preliminary in vitro paclitaxel release studies showed very promising sustained drug release characteristics achieved by these unimolecular micelles. 相似文献
948.
Heme peroxidases are a class of multifunctional redox-active proteins found in all organisms. We recently cloned, expressed, and characterized an ascorbate peroxidase from Leishmania major (LmAPX) that was capable of detoxifying hydrogen peroxide. Localization studies using green fluorescent protein fusions revealed that LmAPX was localized within the mitochondria by its N-terminal signal sequence. Subcellular fractionation analysis of the cell homogenate by the Percoll density-gradient method and subsequent Western blot analysis with anti-LmAPX antibody further confirmed the mitochondrial localization of mature LmAPX. Submitochondrial fractionation analysis showed that the mature enzyme (~3.6 kDa shorter than the theoretical value of the whole gene) was present in the intermembrane space side of the inner membrane. Moreover, expression of the LmAPX gene was increased by treatment with exogenous H(2)O(2), indicating that LmAPX was induced by oxidative stress. To investigate the biological role of LmAPX we generated Leishmania cells overexpressing LmAPX in the mitochondria. Flow-cytometric analysis, thin-layer chromatography, and IC(50) measurements suggested that overexpression of LmAPX caused depletion of the mitochondrial ROS burden and conferred a protection against mitochondrial cardiolipin oxidation and increased tolerance to H(2)O(2). These results suggest that the single-copy LmAPX gene plays a protective role against oxidative damage. 相似文献
949.
V. Vivekanand Pallavi Dwivedi Amit Sharma Nidhi Sabharwal Rajesh P. Singh 《World journal of microbiology & biotechnology》2008,24(12):2799-2804
An environmentally sound biobleaching to get high quality paper pulp from mixed wood pulp was attempted employing laccase
from Aspergillus fumigatus VkJ2.4.5 for lignin removal. Laccase treatment was performed in the presence of a mediator N-hydroxybenzotriazole (HBT, 1.5% w/w), resulting into notably higher level of delignification of the pulp. Enzyme at 10 Ug−1 of pulp at 50°C, pH 6.0, for 2 h with a pulp consistency of 10% was found suitable for enabling maximum decrease in the kappa
number. The kappa number and yellowness decreased by 14 and 4% whereas ISO brightness improved by 7%. The presence of a characteristic
peak at 280 nm indicated the presence of lignin in the effluent during biobleaching. Analysis of FTIR spectra of residual
lignin revealed characteristic modifications following enzymatic bleaching by laccase mediator system (LMS). Variations in
morphology and crystallinity of pulp were evaluated by scanning electron microscopy and X-ray diffraction analysis. 相似文献
950.
Foote KM Mortlock AA Heron NM Jung FH Hill GB Pasquet G Brady MC Green S Heaton SP Kearney S Keen NJ Odedra R Wedge SR Wilkinson RW 《Bioorganic & medicinal chemistry letters》2008,18(6):1904-1909
A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume. 相似文献