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Combination therapy which enhances efficacy and reduces toxicity, has been increasingly applied as a promising strategy for cancer therapy. Here, a reactive oxygen species (ROS) that enhanced combination chemotherapy nanodevices was fabricated based on the Fe-chelated polydopamine (PDA) nanoparticles (NPs). The structure was characterized by dynamic light scattering-autosizer, transmission electron microscopy, energy dispersive spectroscopy, and Fourier-transform infrared (FT-IR) spectrophotometer. The in vitro drug release profile triggered by low intracellular pH indicated that the system demonstrated controlled therapeutic activity. In vitro cell uptake studies showed that doxorubicin (DOX)-loaded Fe-PDA/ folic acid (FA)- polyethylene glycol (DOX@Fe-PDA/FA-PEG) had a strong uptake capacity and can be rapidly internalized by MCF-7 cells. The in vitro experiments demonstrated that DOX@Fe-PDA/FA-PEG triggered the intracellular ROS overproduction, thereby enhancing its therapeutic effect on breast cancer. In summary, this experiment demonstrated the novel DOX-loaded composite NPs used as a potential targeted nanocarrier for breast cancer treatment, which could be a promising therapeutic strategy against breast cancer.

Exploring safe and highly efficient gene carriers made from biocompatible constituents has great prospects for clinical gene therapy. Here, a supramolecular gene delivery system was readily constructed by assembling adamantyl-modified polyethylenimine (PEI-Ada) units with a versatile ruthenium bipyridine-modified cyclodextrin (Ru-CD) through host-guest interactions. The photophysical and morphological features of the PEI-Ada@Ru-CD nanoparticles were systematically characterized by techniques including UV-vis absorption spectroscopy, fluorescence spectroscopy, transmission electron microscopy, dynamic light scattering, and zeta potential experiments. The small size and suitably positive zeta potential of the nanoparticles facilitated their cellular uptake and gene transfection. As expected, DNA interaction studies, which were performed using agarose gel electrophoresis and atomic force microscopy, showed that the ability of the nanoparticles to condense DNA was higher than that of the gold standard, i.e., PEI, at low N/P ratios. The design of these ruthenium-containing supramolecular nanoparticles based on bipyridine-modified cyclodextrin and adamantyl PEI has great prospects in the development of gene delivery vehicles.

Proanthocyanidin (PC) has attracted wide attention on cosmetics and pharmaceutical due to its antioxidant, anticancer, antimicrobial, antiangiogenic, and anti-inflammatory activities. However, PC applications are limited because of its sensitivity to thermal treatment, light, and oxidation and the poor absorption in the gastrointestinal tract. Thus, a novel dosage form of PC needs to be designed to improve its stability and bioavailability for drug delivery. The objective of this study is to fabricate proanthocyanidins/chitosan/lecithin (PC/CTS/LEC) microspheres and investigate various characteristics. In the current study, PC/CTS/LEC microspheres were prepared by spray-drying technology. The yield (61.68%), encapsulation efficiency (68.19%), and drug loading capacity (17.05%) were found in the results. The scanning electron microscope demonstrated that the microspheres were spherical in shape with wrinkled surfaces. DSC study displayed that the microspheres stability was greatly improved when comparing with bare PC. The in vitro release study showed that the 76.92% of PC was released from microspheres within 48 h. The moisture contents of microspheres ranged from 8% to 13%. The swelling rate and tapped density of microspheres were elevated with increasing the concentration of chitosan in the formulations. The moisture uptake of microspheres was saturated at 40°C/RH75% within 12 h. Our results indicated that the stability of PC/CTS/LEC microspheres was enhanced, and it is a promising carrier for sustained drug delivery system.

N-[(2-Hydroxyl)-propyl-3-trimethyl ammonium] chitosan chloride (HTCC), a hydrosoluble chitosan derivative, has been extensively investigated as a class of drug delivery vehicles because of its unique features. However the studies on HTCC for pulmonary delivery systems have been rarely conducted. This study aimed to design porous microspheres (MS) containing cyclosporine A (CsA) using HTCC as the carrier. The physicochemical properties and biocompatibility of the MS were evaluated. The in vivo efficacy of MS was evaluated in an asthmatic rat model after pulmonary administration. The results showed that porous MS suitable for inhalation could be readily produced by spray drying method. Optimized porous MS in this study exhibited to be biocompatible and safe to use in the lung, and they were effective in suppression of inflammation in the asthmatic rat model. Above all, our results suggested that HTCC porous MS are promising drug carriers for pulmonary drug delivery.

A series of new 1,2,3-triazole derivatives were synthesized and evaluated for anticholinesterase and neuroprotective activities. Some synthetic derivatives, especially compound 32, exhibited improved acetylcholinesterase (AChE) inhibitory activity by comparison with the hit 1, high selectivity toward AChE over butyrylcholinesterase (BuChE), and suitable in vitro neuroprotective effect against amyloid-β25-35 (Aβ25-35)-induced neurotoxicity in SH-SY5Y cells. Furthermore, these molecules have desired physicochemical properties in the range of CNS drugs and showed no cytotoxicity against two normal cells, including human keratinocytes HaCaT and murine fibroblasts NIH-3T3. The preliminary bioassay results and docking study indicated that compound 32 might be a promising lead compound with dual action for the treatment of Alzheimer's disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Ab initio calculations on potential energy curves (PECs), spectroscopic constants, transition dipole moments, radiative transition probabilities and lifetimes for the ground state (X(2)Σ(+)) and the first excited state (A(2)Π) of MgX (X=F, Cl, Br, I) molecules are determined by high-level internally contracted multi-reference configuration interaction (ic-MRCI) method. In order to improve the calculation, the Davidson modification (+Q) and scalar relativistic correction are included. The present results show that most of spectroscopic constants are in accordance with the measurements, the equilibrium internuclear distance Re increases while the other spectroscopic constants reduce along with the increasing of the atomic number of the halogen from F to I. Diagonal vibrational transitions are found to be dominant for the A(2)Π→X(2)Σ(+) system of MgX molecules. The corresponding radiative lifetimes of ν'=0 are computed to be 7.24, 9.98, 18.94 and 22.72 ns for MgF, MgCl, MgBr, and MgI, respectively. The calculated result of MgF molecule is in good agreement with the recent theoretical result of 7.16 ns, with a small relative error percent of 1.11%., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Developing anticancer agents by a prooxidant strategy has attracted increasing attention in recent years, although it is not conventional in medicinal chemistry and is completely opposite to antioxidant therapy. In this work, a panel of diarylpentanoids as the curcumin mono-carbonyl analogs were designed and synthesized, and their cytotoxic and proapoptotic mechanisms against human lung cancer A549 cells were investigated at the frontiers of chemistry and biology. It was found that compared with curcumin, the compounds (A1, B1, and C1) bearing two ortho substituents on the aromatic rings, especially A1, exhibit significantly increased cytotoxic and proapoptotic activities through a Michael acceptor unit-dependent prooxidant-mediated mechanism. The prooxidative ability is governed not only by their electrophilicity but also by their geometry, cellular uptake and metabolic stability, and TrxR-inhibitory activity. Mechanistic investigation reveals that the compound A1 could effectively and irreversibly modify the TrxR by virtue of the above optimal biochemical parameters, and convert this antioxidant enzyme into a reactive oxygen species (ROS) promoter, resulting in a burst of the intracellular ROS including H2O2 and O2(-)•. The ROS generation is associated with falling apart in the redox buffering system, and subsequently induces increases in Ca(2+) influx and oxidative stress, collapse of mitochondrial membrane potential, and activation of caspase-9 and caspase-3, ultimately leading to cell apoptosis. This work highlights the feasibility in designing curcumin-inspired anticancer agents by a prooxidant strategy, and gives us useful information on how to design them., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Resveratrol (3,5,4'-trihydroxystilbene, RES), a star among dietary polyphenols, shows a wide range of biological activities, but it is rapidly and extensively metabolized into its glucuronide and sulfate conjugates as well as to the corresponding reduced products. This begs the question of whether the metabolites of RES contribute to its in vivo biological activity. To explore this possibility, we synthesized its glucuronidation (3-GR and 4'-GR) and reduction (DHR) metabolites, and evaluated the effect of these structure modifications on biological activities, including binding ability with human serum albumin (HSA), antioxidant activity in homogeneous solutions and heterogeneous media, anti-inflammatory activity, and cytotoxicity against various cancer cell lines. We found that 1) 4'-GR, DHR and RES show nearly equal binding to HSA, mainly through hydrogen bonding, whereas 3-GR adopts a quite different orientation mode upon binding, thereby resulting in reduced ability; 2) 3-GR shows comparable (even equal) ability to RES in FRAP- and AAPH-induced DNA strand breakage assays; DHR, 3-GR, and 4'-GR exhibit anti-hemolysis activity comparable to that of RES; additionally, 3-GR and DHR retain some degree activity of the parent molecule in DPPH.-scavenging and cupric ion-initiated oxidation of LDL assays, respectively; 3) compared to RES, 4'-GR displays equipotent ability in the inhibition of COX-2, and DHR presents comparable activity in inhibiting NO production and growth of SMMC-7721 cells. Relative to RES, its glucuronidation and reduction metabolites showed equal, comparable, or some degree of activity in the above assays, depending on the specific compound and test model, which probably supports their roles in contributing to the in vivo biological activities of the parent molecule., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Five hydroxylated phenanthrenes as "cis-configuration-fixed" resveratrol analogues differing in the number and position of the hydroxyl groups were designed and synthesized. Their antioxidant activity was studied by ferric reducing antioxidant power, 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging, and DNA strand breakage-inhibiting assays, corresponding to their electron-donating, hydrogen-transfer and DNA-protecting abilities, respectively. In the above assays, their activity depends significantly on the number and position of the hydroxyl groups, and most of them are more effective than resveratrol. Noticeably, compound 9b (2,4,6-trihydroxyl phenanthrene) with the same hydroxyl group substitutions as resveratrol, is superior to the reference compound, highlighting the importance of extension of the conjugation over multiple aromatic-rings. Similar activity sequences were obtained in different experimental models, but the appreciable differences could contribute detailed insights into antioxidant mechanisms. Based on these results, the hydroxylated phenanthrenes may be considered as a novel type of resveratrol-directed antioxidants., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Development of potential cancer treatment strategies by using an exogenous reactive oxygen species (ROS)-generating agent (prooxidant) or redox intervention, has attracted much interest. One effective ROS generation method is to construct a prooxidant system by polyphenolic compounds and Cu(II) ions. This work demonstrates that Cu(II) and the stilbene-chroman hybrid with a catechol moiety could synergistically induce pBR322 plasmid DNA damage, as well as cell cycle arrest and apoptosis of HepG2 cells. Additionally, an interesting acid/base-promoted prooxidant reaction was found. The detailed chemical mechanisms for the reaction of the hybrid with Cu(II) in acid, neutral and base solutions are proposed based on UV/Vis spectral changes and identification of the related oxidative intermediates and products., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An efficient catalytic system for biomass oxidation to form formic acid was developed. The conversion of glucose to formic acid can reach up to 52% yield within 3 h when catalyzed by 5 mol% of H(5)PV(2)Mo(10)O(40) at only 373 K using air as the oxidant. Furthermore, the heteropolyacid can be used as a bifunctional catalyst in the conversion of cellulose to formic acid (yield=35%) with air as the oxidant., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the past decade, there was a great deal of interest and excitement in developing more active antioxidants and cancer chemoprevention agents than resveratrol, a naturally occurring stilbene. In this work, eight resveratrol-directed 4-mercaptostilbenes were constructed based on the inspiration that thiophenol should be a stronger radical scavenger than phenol, and their reaction rates with galvinoxyl (GO(.)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH(.)) radicals in methanol and ethyl acetate were measured by using stopped-flow UV/Vis spectroscopy at 25 °C. Kinetic analysis demonstrates that 4-mercaptostilbenes are extraordinary radical scavengers, and the substitution of the 4-SH group for the 4-OH group in the stilbene scaffold is an important strategy to improve the radical-scavenging activity of resveratrol. Surprisingly, in methanol, some of the 4-mercaptostilbenes are 10(4)-times more active than resveratrol, dozens of times to hundreds of times more effective than known antioxidants (α-tocopherol, ascorbic acid, quercetin, and trolox). The detailed radical-scavenging mechanisms were discussed based on acidified-kinetic analysis. Addition of acetic acid remarkably reduced the GO(.) and DPPH(.) radical-scavenging rates of the 4-mercaptostilbenes in methanol, a solvent that supports ionization, suggesting that the reactions proceed mainly through a sequential proton loss electron transfer mechanism. In contrast, an interesting acid-promoted kinetics was observed for the reactions of the 4-mercaptostilbenes with DPPH(.) in ethyl acetate, a solvent that weakly supports ionization. The increased ratio in rates is closely correlated with the electron-rich environment in the molecules, suggesting that the acceleration could benefit from the contribution of the electron transfer from the 4-mercaptostilbenes and DPPH(.). However, the addition of acetic acid had no influence on the GO(.)-scavenging rates of the 4-mercaptostilbenes in ethyl acetate, due to the occurrence of the direct hydrogen atom transfer. Our results show that the radical-scavenging activity and mechanisms of 4-mercaptostilbenes depends significantly on the molecular structure and acidity, the nature of the attacking radical, and the ionizing capacity of the solvent., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The adsorption of six free radicals (FRs) respectively on a graphene fragment was studied using a density functional tight-binding method with the inclusion of an empirical dispersion term in total energy. The results indicate that the different interaction paths between the FRs and the graphene lead to different forms of physical (PA) or chemical adsorptions (CA). The CA appears only in the condition where some of the nonhydrogen atoms are closer to the graphene, with the deformation occurring in the latter. The charge transfer increases with the increase in adsorption energy in every FR-graphene system. Although the deformation in the graphene is negligible in all PA cases, the FR is closer to the graphene and the graphene deformation is clearer in all CA cases, with all atomic displacements being larger than 0.1 Å. Our findings are useful not only for FR scavenging but also for studying the interaction between general molecules and material surfaces., (Copyright © 2011 Wiley Periodicals, Inc.)

Resveratrol is the subject of intense research as a natural antioxidant and cancer chemopreventive agent. There has been a great deal of interest and excitement in understanding its action mechanism and developing analogs with antioxidant and cancer chemoprevention activities superior to that of the parent compound in the past decade. This work delineates that elongation of the conjugated links is an important strategy to improve the antioxidant activity of resveratrol analogs, including hydrogen atom- or electron-donating ability in homogeneous solutions and antihemolysis activity in heterogeneous media. More importantly, C3, a triene bearing 4,4'-dihydroxy groups, surfaced as an important lead compound displaying remarkably increased antioxidant, cytotoxic, and apoptosis-inducing activities compared with resveratrol., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The 355 nm laser pulse from THG (Third Harmonic Generation) of a Qswitched Nd3+ : YAG laser was used to ablate silicon mounted in air. The time-and space-resolved optical emission spectra were measured for different pulse energy in the wavelength range of 380-420 nm, the emission spectra of N+ was found for impact ionization of air near target surface on the early stage of plasma plume expansion. Under the model of local thermodynamic equilibrium, the electronic temperature of plasma was deduced to be in the range of 18 000-40 000 K using the Saha equation by the relative line intensities, and the electron density was deduced to be in the 10(17) cm(-3) scale by FWHM (the full width at half maximum) of Si spectral lines, the temporal and spatial evolution of the electronic temperature and electron density was given, showing that the electronic temperature and electron density exhibited second order exponential decreasing with laser delay time and a Lorentz distribution in space. The reason for the spatial position deviation of the maximum electron density from the maximum spectral intensity was analyzed. The relationship between the plasma plume parameters and laser pulse energy was discussed.

Objective: To understand the influence of different sleep stages on respiratory regulation in normal people., Methods: We measured ventilation (VE) and occlusion pressure (P0.1) responses to hyperoxia hypercapnia (deltaVE/deltaPaCO2, deltaP0.1/deltaPaCO2) and isocapnic hypoxia (deltaVE/deltaSaO2 and deltaP0.1/deltaSaO2) in eleven non-snoring healthy people during wakefulness and during non-rapid eye movement (NREM) I + II, NREM III+IV, and rapid eye movement (REM) sleep stages., Results: During NREM I + II and NREM III+IV, the normal subjects showed no significant decrease in P0.1, deltaP0.1/deltaSaO2 and deltaP0.1/deltaPaCO2 (P > 0.05), but deltaVE/ deltaSaO2 and deltaVE/ deltaPaCO2 decreased significantly (P < 0.05). During REM sleep, P0.1 maintained the level during wakefulness, but both hypoxic and hypercapnic responses decreased significantly (P < 0.05)., Conclusions: Sleep has significant influence on respiratory regulation in normal people. The respiratory drive (P0.1) in both NREM and REM sleep stages could maintain the awake level due to an effective compensation to the increase of upper airway resistance. The P0.1 responses to both hypoxia and hypercapnia decrease only in REM sleep stage, which is in consistent with the clinical phenomenon that sleep disordered breathing occurs in REM in normal people.

Objective: It is assumed that the reduced ventilatory control during sleep may be related to the nocturnal hypoxia in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and daytime CO(2) retention., Methods: Oxygen desaturation index (ODI(4)), sleep time spent when SaO(2) was below 90% (SIT(90)), the lowest SaO(2) (LSaO(2)) and the mean SaO(2) (MSaO(2)) during sleep were measured in 24 OSAHS patients with daytime PaCO(2) > or = 45 mm Hg and 39 with PaCO(2) < 45 mm Hg. Hypoxic (DeltaP(0.1)/DeltaSaO(2)) and hypercapnic (DeltaP(0.1)/DeltaPaCO(2)) responsiveness were measured in 11 eucapnic and 4 hypercapnic patients during wakefulness, NREM and REM sleep stages., Results: Compared with the eucapnic patients, all the hypercapnic patients had more severe hypoxia during sleep (P < 0.05). Although both groups had similar chemical responsiveness during wakefulness, the hypercapnic patients had lower DeltaP(0.1)/DeltaSaO(2) and DeltaP(0.1)/DeltaPaCO(2) during both REM and NREM sleep (P < 0.05)., Conclusion: The depressed chemical responsiveness during sleep plays an important role in the development of nocturnal hypoxia in OSAHS patients with daytime CO(2) retention.

Objectives: To study the association of narcolepsy with HLA class II alleles in Chinese narcoleptic patients., Methods: 31 patients with narcolepsy underwent brain computed tomography (CT) scan and magnetic resonance imaging (MRI) testing. All patients received a MSLT test following a routine night's sleep, and serological HLA typing for HLA DR(2). 21 patients received PCR-SSP HLA DR and DQ typing., Results: All patients had sleepiness and cataplexy. There was no evidence for other functional or structural diseases. Sleep paralysis was elicited in 45%; hypnagogic hallucinations, in 61%. Mean sleep latency on MSLT was 2.1 min +/- 1.3 min; sleep-onset rapid eye movement (SOREM) occurred during 2/5 naps in 30 of 31 patients. The average number and latency of SOREM episodes were 4.2 +/- 1.0 episodes and 4.0 min +/- 1.8 min, respectively. All patients but one were HLA DR(2) positive and 86% were HLADRB(1) * 1501-HLADQB(1)*0602 positive., Conclusions: HLA DR(2) and HLADQw6 are markers for narcolepsy-cataplexy in Chinese.

Twelve subjects with COPD in acute exacerbation of respiratory failure were studied. The experiment of each subject was divided into three steps: room air breathing, 35% O2 inhalation for one hour, and then intravenous drip of nikethamide (1.875g) for two hours with 35% oxygen inhalation at the same time. At the end of each step, mouth occlusion pressure (P0.1), VT, VE, VA, VCO2, VD and PaO2, PaCO2 were measured respectively. The results showed that, when breathing air, all the patients presented significant higher P0.1 than normal subjects, indicated higher central drive. After oxygen inhalation, P0.1 decreased markedly, but still higher than normal. No correlation was found between delta P0.1 and delta PaO2. VE declined with the drop of P0.1, but this was due to a decrease of respiratory frequency, while VA remained unchanged (P > 0.05). The increase of PaCO2 was unremarkable. Neither correlation was found between delta VA and delta P0.1, nor between delta VA and delta PaCO2. However, a close correlation existed between delta VCO2/VCO2 and delta VE/VE. The result of our study is not consistent with the postulation, the removal of the hypoxic stimulate after oxygen administration results in a decrease of ventilation and CO2 retention. After nikethamide administration, P0.1 increased as well as VE while VA and PaCO2 remained unchanged. The increase of VE was caused by the increase of respiratory rate. Furthermore, PaO2 decreased in some patients. All of the changes demonstrated that nothing is worthwhile with the treatment of nikethamide, but a side effect from increasing work of breathing and consumption of oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to study the relationship between the acute lower respiratory tract infection (ALRTI) during childhood and the occurrence of chronic bronchitis in adults, 90 cases (infection group) admitted to hospital for ALRTI before 7 yr old were followed up 24-31 years later. Their siblings without ALRTI during childhood were selected as the control group. The prevalence of chronic bronchitis in the infection group (12.2%) is significantly higher than that of the control group (2.2%). It is concluded that ALRTI during childhood may play an important role in the occurrence of chronic bronchitis in adults. Further analysis showed that infection and smoking have synergic effects on the occurrence of chronic bronchitis.

In order to study the nature of chronic asthmatic bronchitis, we compared the clinical features of patients with chronic asthmatic bronchitis, bronchial asthma and simple chronic bronchitis. We also measured FEV1 on these patients before and after inhaling 1% isoproterenol aerosol as well as after administration of oral prednisone (40 mg/day) for a week. The results showed that there was little difference in terms of precipitating factors, attacking features, premonitory symptoms, developing course and relieving measures between the patients with chronic asthmatic bronchitis and bronchial asthma. The improved percentage of FEV1 (more than 15%) on the patients with chronic asthmatic bronchitis after inhalation of bronchodilator aerosol and administration of oral prednisone showed no significant difference from that of bronchial asthma. We suggest that the former term be replaced by the term of chronic bronchitis associated with asthma. It can probably avoid the confusion on the diagnosis of chronic bronchitis and bronchial asthma.

We examined the effects of lung volume on the bronchoconstriction induced by inhaled aerosolized methacholine (MCh) in seven normal subjects. We constructed dose-response curves to MCh, using measurements of inspiratory pulmonary resistance (RL) during tidal breathing at functional residual capacity (FRC) and after a change in end-expiratory lung volume (EEV) to either FRC -0.5 liter (n = 5) or FRC +0.5 liter (n = 2). Aerosols of MCh were generated using a nebulizer with an output of 0.12 ml/min and administered for 2 min in progressively doubling concentrations from 1 to 256 mg/ml. After MCh, RL rose from a base-line value of 2.1 +/- 0.3 cmH2O. 1-1 X s (mean +/- SE; n = 7) to a maximum of 13.9 +/- 1.8. In five of the seven subjects a plateau response to MCh was obtained at FRC. There was no correlation between the concentration of MCh required to double RL and the maximum value of RL. The dose-response relationship to MCh was markedly altered by changing lung volume. The bronchoconstrictor response was enhanced at FRC - 0.5 liter; RL reached a maximum of 39.0 +/- 4.0 cmH2O X 1-1 X s. Conversely, at FRC + 0.5 liter the maximum value of RL was reduced in both subjects from 8.2 and 16.6 to 6.0 and 7.7 cmH2O X 1-1 X s, respectively. We conclude that lung volume is a major determinant of the bronchoconstrictor response to MCh in normal subjects. We suggest that changes in lung volume act to alter the forces of interdependence between airways and parenchyma that oppose airway smooth muscle contraction.