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Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NH
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Objective To construct a novel thiolated chitosan modified poly(lactide-co-ε-caprolactone)-d-α-tocopheryl polyethylene glycol 1 000 succinate (PLA-PCL-TPGS) nanoparticle,and investigate the feasibility of its use as an oral carrier for lung cancer chemotherapy.Methods The PLA-PCL-TPGS random copolymer was synthesized and characterized.Then three types of nanoparticles from commercial PCL and PLA-PCL-TPGS random copolymer were prepared for oral carrier of paclitaxel,including 5％ thiolated chitosan-modified PCL nanoparticles (CNPs),unmodified PLA-PCL-TPGS nanoparticles (UNPs),and 5％ thiolated chitosan-modified PLA-PCL-TPGS nanoparticles (TNPs).The prepared nanoparticles were characterized in terms of size,Zeta potential,morphology,drug loading and encapsulation efficiency.The in vitro drug release profiles and cellular uptake of the nanoparticles by human lung cancer cell lines A549 cells were investigated,and cytotoxicity against A549 cells was also evaluated.The evened sac method was used for the measurement of transportation of paclitaxel across the intestine barrier.Results The field emission scanning electron microscopy results showed that the three types of paclitaxel-loaded nanoparticles were spherical with a diameter about 200 nm.The surface charge of PLA-PCL-TPGS nanoparticles was reversed from negative to positive charge after thiolated chitosan modification.The UNPs and TNPs achieved higher drug loading,encapsulation efficiency and drug release after 32 d than CNP (all P＜0.05).The TNPs had significantly higher cell uptake efficiency than that of CNPs and UNPs (all P＜0.05).In vitro cell viability studies showed advantages of TNPs over a clinically available paclitaxel injection in terms of cytotoxicity against A549 cells.Ex vivo absorption studies revealed that the TNPs can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein.Conclusion PLA-PCL-TPGS nanoparticles modified by thiolated chitosan can enhance the cellular uptake and cytotoxicity,which reveals a potential application for oral chemotherapy of lung cancer.
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AIM: To explore the neuroprotective effect of fasudil combined with bone marrow -derived neural stem cells ( BM-NSCs) on the mice with experimental autoimmune encephalomyelitis ( EAE).METHODS: Female C57BL/6 mice (8~10 weeks old, n=32) were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) to establish chronic EAE model .The mice were randomly divided into control ( ddH2 O ) group, fasudil group , BM-NSCs group , and fasudil+BM-NSCs group .The clinical score and body weight were recorded every other day .The expression of neurotrophic factors was determined by immunofluorescence staining .RESULTS:In comparison with ddH2O group, fasud-il combined with BM-NSCs delayed onset and ameliorated severity of EAE .The numbers of brain-derived neurotrophic fac-tor, glial cell-derived neurotrophic factor , nerve growth factor , neurotrophin-3 and ciliary neurotrophic factor positive cells in fasudil group, BM-NSCs group and fasudil +BM-NSCs group were all increased in various extents .In particularly, the expression of these neurotrophic factors in fasudil +BM-NSCs group was significantly higher than that in the mice treated with fasudil or BM-NSCs alone (P<0.01).CONCLUSION:Fasudil combined with BM-NSCs promotes the expression of neurotrophic factors and improves microenvironment of central nervous system , thus playing a positive role in neural restora-tion and regeneration through a synergistic and superimposed effect .
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AIM:To explore the therapeutic effect of a novel Rho kinase inhibitor FSD-C10 onβ-amyloid pro-tein precursor (APP)/presenilin-1 (PS1) double transgenic mice.METHODS: The transgenic mice overexpressing hu-man APP with the Swedish mutation (695) and human PS1 with ΔE9 mutation at the age of 8 months were used in this study.The mice were randomly divided into model group and FSD-C10 intervention group, and wild-type mice at the same age served as normal controls .The mice in FSD-C10 intervention group were treated with FSD-C10 (25 mg· kg-1 · d-1 ) for 2 months by intraperitoneal injection .The mice in model group and the wild-type mice were injected with saline in the similar manner.Morris water maze (MWM) test was applied to examine the capacity of learning and memory .The Aβ1-42 deposition, Tau protein phosphorylation , and the expression of β-site APP-cleaving enzyme ( BACE) as well as inflammato-ry molecules, such as TLR-4 and NF-Κb, and M1/M2 microglial markers, such as Inos and Arg-1, were determined by the methods of immunohistochemistry and Western blot .RESULTS: Compared with model group , FSD-C10 significantly improved the learning and memory abilities of APP/PS1 double transgenic mice , accompanied by reduced Aβ1-42 deposi-tion, Tau protein phosphorylation and BACE expression in the hippocampus .The intervention of FSD-C10 decreased the protein levels of TLR-4 and p-NF-Κb, reduced the expression of Inos and increased the expression of Arg-1 in the brain tissues.CONCLUSION:The novel Rho kinase inhibitor FSD-C10 improves the capacity of spatial learning and memory in APP/PS1 double transgenic mice , which may be related to the inhibition of TLRs/NF-Κb signaling pathway , the reduction of the secretion of inflammatory molecules and the polarization of anti-inflammatory M2 microglia, thus improving the in-flammatory microenvironment of the brain in APP/PS1 double transgenic mice .
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AIM:To explore the therapeutic effect of a novel Rho kinase inhibitor FSD-C10 onβ-amyloid pro-tein precursor (APP)/presenilin-1 (PS1) double transgenic mice.METHODS: The transgenic mice overexpressing hu-man APP with the Swedish mutation (695) and human PS1 with ΔE9 mutation at the age of 8 months were used in this study.The mice were randomly divided into model group and FSD-C10 intervention group, and wild-type mice at the same age served as normal controls .The mice in FSD-C10 intervention group were treated with FSD-C10 (25 mg· kg-1 · d-1 ) for 2 months by intraperitoneal injection .The mice in model group and the wild-type mice were injected with saline in the similar manner.Morris water maze (MWM) test was applied to examine the capacity of learning and memory .The Aβ1-42 deposition, Tau protein phosphorylation , and the expression of β-site APP-cleaving enzyme ( BACE) as well as inflammato-ry molecules, such as TLR-4 and NF-Κb, and M1/M2 microglial markers, such as Inos and Arg-1, were determined by the methods of immunohistochemistry and Western blot .RESULTS: Compared with model group , FSD-C10 significantly improved the learning and memory abilities of APP/PS1 double transgenic mice , accompanied by reduced Aβ1-42 deposi-tion, Tau protein phosphorylation and BACE expression in the hippocampus .The intervention of FSD-C10 decreased the protein levels of TLR-4 and p-NF-Κb, reduced the expression of Inos and increased the expression of Arg-1 in the brain tissues.CONCLUSION:The novel Rho kinase inhibitor FSD-C10 improves the capacity of spatial learning and memory in APP/PS1 double transgenic mice , which may be related to the inhibition of TLRs/NF-Κb signaling pathway , the reduction of the secretion of inflammatory molecules and the polarization of anti-inflammatory M2 microglia, thus improving the in-flammatory microenvironment of the brain in APP/PS1 double transgenic mice .
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<p><b>BACKGROUND</b>A positive association between the ABO blood types and survival has been suggested in several malignancies. The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of Chinese patients with curatively resected non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>We retrospectively analyzed 1601 consecutive Chinese patients who underwent curative surgery for NSCLC between January 1, 2005 and December 31, 2009. The relationship between the ABO blood types and survival was investigated. In addition, univariate and multivariate analyses were performed.</p><p><b>RESULTS</b>Group 1 (patients with the blood type O or B) had significantly prolonged overall survival (OS) compared with group 2 (patients with the blood type A or AB), with a median OS of 74.9 months versus 61.5 months [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.72-0.96; P = 0.015]. Additionally, group 1 had significantly longer disease-free survival (DFS; HR 0.86; 95% CI 0.76-0.98; P = 0.022) and locoregional relapse-free survival (LRFS; HR 0.79; 95% CI 0.64-0.98; P = 0.024) than group 2. The association was not significantly modified by other risk factors for NSCLC, including smoking status, pathologic tumor-node-metastasis stage, pT category, pN category, and chemotherapy.</p><p><b>CONCLUSIONS</b>There is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC. Patients with the blood type O or B had significantly prolonged OS, DFS, and LRFS compared with those with the blood type A or AB.</p>