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Lymphatic vessels are essential for tissue fluid homeostasis, immune cell trafficking, and intestinal lipid absorption. The lymphatics have long been recognized to serve as conduits for distant tumor dissemination. However, recent findings suggest that the regional lymphatic vasculature also shapes the immune microenvironment of the tumor mass and potentiates immunotherapy. This review discusses the role of lymphatic vessels in tumor metastasis and tumor immunity.
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Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.
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Objective To investigate antimicrobial resistance of Escherichia coli (E.coli)and Klebsiella pneumoniae (K.pneumoniae),antimicrobial use density(AUD),as well as relation between antimicrobial resistance and AUD in a ter-tiary first-class hospital.Methods Antimicrobial resistance rates of clinically-isolated E.coli and K.pneumoniae,AUD of carbapenems and quinolones,as well as relation between resistance and AUD in 2013-2015 were statistically analyzed. Results Correlation analysis of antimicrobial resistance of bacteria and AUD showed that the decrease in resistance rate of E.coli to levofloxacin was related to the decrease in the use density of quinolones(r=0.61,P=0.03);increase in resist-ance rate of K.pneumoniae to imipenem was related to the increase in the use density of carbapenems(r=0.78,P<0.01). Conclusion Antimicrobial use is one of the causes of bacterial resistance,management on antimicrobial use needs to be strengthened to reduce the threat of bacterial resistance to human health.
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In recent years, the development of molecular biology and medicine has prompted the research of gene therapy for brain diseases. In this review, we summarized the current gene therapy approaches of major brain diseases. Against the pathogenesis of major brain diseases, including brain tumors, Parkinson's disease, Alzheimer's disease and cerebrovascular disorders, there are several effective gene therapy strategies. It is no doubt that, gene therapy, as a novel treatment, is of great significance for understanding the causes, as well as comprehensive treatment for brain diseases.
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Purpose To optimize the preparation of NC-1900 loaded MePEG-PLA nanoparticles (NPs). Methods MePEG-PLA copolymers of different molecular weight synthesized by solvent poly-merization method were used to prepare NC-1900 loaded MePEG-PLA NPs by double emulsion/solvent evaporation method.Orthogonal experimental design and multiple regressions were used to optimize the preparation method with nanoparticle size and NC-1900 encapsulation efficiency (EE) as res-ponse variables.NPs were characterized by particle size and Zeta potential detector and transmission electron microscope.The leakage of NC-1900 from NPs was evaluated by high-performance liquid chromatography (HPLC) detection. Results MePEG3000-PLA44800 NPs prepared according to the optimized conditions had a mean diameter of (77 ± 11) nm and EE of (21.4 ± 0.1) %.Only 5% and 15% of NC-1900 were leaked in pH 7.4 PBS and blank plasma at the end of 48 h,respectively. Conc-lusions The optimized MePEG3000-PLA44800 NPs is a favorable carrier for NC-1900.
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Aim A method of coculture of brain capillary endothelial cells (BCECs) and astrocytes of rats was used to evaluate nanoparticle' s blood-brain barrier (BBB) transcytosis and toxicity at the endothelial tight junction. Methods A lipophilic fluorescent probe, 6-coumarin, was incorporated in poly(ethyleneglycol)-poly (lactide) nanoparticle using double emulsion/solvent evaporation method. BCECs and astrocytes were firstly isolated from brain of newborn rats and characterized by their morphology and immunocytochemistry staining, separately. Subsequently, a coculture model with BCECs on the top of micro-porous membrane of cell culture insert and astrocytes on the bottom side was established. The permeability of 14C-labeled sucrose and nanoparticle were determined, separately. Results The meanweight-based diameter of 6-coumarin loaded nanoparticles was ( 102.4 ± 6.8) nm, with zeta potential of ( - 16.81 ± 1.05) mV. BCECs were positive for factor Ⅷ staining and glial fibrillary acidic protein was tight junction between BCECs in the coculture model could be visualized by both scanning electron microscopy and transmission electron microscopy. The unchanged paracellular transport of sucrose proved vivo situation for examination of the permeability of nanoparticle and toxicity evaluation.
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Aim To investigate the extent of systemic absorption and uptake of meptazinol (MEP) hydrochloride in cerebrospinal fluid (CSF) after intranasal administration on rats and compare with oral administration. Methods CSF samples were collected by a serial sampling method. The concentration of MEP in the biological samples was measured by HPLC with fluorescence detector. Results Rapid and significant levels of MEP in plasma and CSF can be achieved after nasal administration whereas the oral administration resulted in considerably lower drug concentrations. AUC in plasma and CSF from the nasal route are 7.375 and 15.6 folds compared with those of the oral route, respectively. Conclusion Intranasal MEP is able to show quick absorption and improve the bioavailability, which could be a promising alternative to oral administration.