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1.
Huan Jing Ke Xue ; 41(6): 2586-2595, 2020 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608772

RESUMO

As important precursors of near-surface ozone, secondary organic aerosols (SOAs), and volatile organic compounds (VOCs) play an important role in photochemical reactions and fine particle formation. In this study, real-time VOCs were measured continuously by Syntech Spectras GC955 analyzers at the regional background site of the North China Plain from September 1 to 27, 2017. The VOC concentration levels, compositions, spatiotemporal variations, and the ozone formation potential during the observation period were investigated. The potential sources of initial VOCs indicated from the diagnostic ratios were further studied. The averaged total mixing ratio of VOCs was 12.53×10-9. Among all measured VOC species, alkanes were the most abundant species, which accounted for 65.3% of the total concentrations, followed by alkenes (26.7%) and aromatics (6.5%). In addition, the total OH radical loss rate of VOCs (L·OH) was 5.2 s-1. In particular, the contribution of C4-C5 alkenes to L·OH was as high as 61%, followed by C2-C3 alkenes, with a 12.8% contribution of L·OH. The average ozone formation potential of VOCs was 36.5×10-9. Among all the measured VOC species, alkenes were the most abundant species, which accounted for 71.2%. Among alkenes, the contribution of C4-C5 alkenes was the most prominent. Although the concentration of alkanes in Shangdianzi was much higher than other VOC species, the ozone formation potential was lower. Diagnostic ratios and source implications suggested that Shangdianzi was affected mainly by biomass/biofuel/coal burning, with substantially elevated benzene levels during the observation period, whereas a slight influence of traffic-related emissions was observed.

2.
Oxid Med Cell Longev ; 2020: 6841581, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32566095

RESUMO

Persistent senescence seems to exert detrimental effects fostering ageing and age-related disorders, such as cancer. Chemotherapy is one of the most valuable treatments for cancer, but its clinical application is limited due to adverse side effects. Melatonin is a potent antioxidant and antiageing molecule, is nontoxic, and enhances the efficacy and reduces the side effects of chemotherapy. In this review, we first summarize the mitochondrial protective role of melatonin in the context of chemotherapeutic drug-induced toxicity. Thereafter, we tabulate the protective actions of melatonin against ageing and the harmful roles induced by chemotherapy and chemotherapeutic agents, including anthracyclines, alkylating agents, platinum, antimetabolites, mitotic inhibitors, and molecular-targeted agents. Finally, we discuss several novel directions for future research in this area. The information compiled in this review will provide a comprehensive reference for the protective activities of melatonin in the context of chemotherapy drug-induced toxicity and will contribute to the design of future studies and increase the potential of melatonin as a therapeutic agent.

3.
Colloids Surf B Biointerfaces ; 194: 111144, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32535244

RESUMO

Histonedeacetylase inhibitor (HDACi) has great potential in targeted antitumor therapy by inhibiting tumor migration, invasion, and metastasis. As one of the typical HDACis, vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) was approved as a therapeutic agent for cancer therapy, however, challenges remain due to their poor solubility, short half-life and low efficiency in cellular penetration. Considering the disadvantages of usual drug carriers, folate and vorinostat bound BSA nanogel (FVBN)was fabricated to implement higher solubility, stability, cellular uptake, and lipase-responsive release. With good dispersion and stability, FVBN significantly increased the cellular uptake of vorinostat through folate-mediated endocytosis. FVBN exhibited comparable cytotoxicity with free SAHA, and the growth of tumor cells was blocked in G1/G0 phase just like SAHA performed in cell cycle arrest tests. Moreover, FVBN not only effectively inhibited the growth of melanoma but also observably prevented pulmonary metastasis of melanoma. In the experiment against nude mice bearing solid ovarian cancer, FVBN showed excellent antitumor effect without liver damage, demonstrating the superiority of gelated and inner-lysosome triggered release strategies to the free SAHA, and it is promising to expand the scope of application of HDACi in clinical cancer therapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32373063

RESUMO

Aim: Melatonin is an indolamine secreted by the pineal gland, as well as most of the organs and tissues. In addition to regulating circadian biology, studies have confirmed the multiple pharmacological effects of melatonin. Melatonin provides a strong defense against septic myocardial injury. However, the underlying mechanism has not been fully described. In this study, we investigated the protective effects of melatonin against lipopolysaccharide (LPS)-induced myocardial injury as well as the mechanisms involved. Methods: Mice were intraperitoneally injected with LPS to induce a septic myocardial injury model or an LPS shock model, depending on the dose of LPS. Melatonin was given (20 mg/kg/day, via intraperitoneal injection) for a week prior to LPS insult. 6 h after LPS injection, echocardiographic analysis, TUNEL staining, transmission electron microscopy (TEM), western blot, quantitative real-time PCR and ELISA were used to investigate the protective effects of melatonin against LPS induced myocardial injury. AMPK inhibitor, autophagy activator and inhibitor, siRNAs were used for further validation. Results: Survival test showed that melatonin significantly increased the survival rate after LPS-induced shock. In the sepsis model, melatonin markedly ameliorated myocardial dysfunction, decreased the release of inflammatory cytokines, activated AMP-activated protein kinase (AMPK), improved mitochondrial function, and activated autophagy. To confirm whether the protection of melatonin was mediated by AMPK and autophagy, Compound C, an AMPK inhibitor; 3-MA, an autophagy inhibitor; and Rapamycin (Rapa), an autophagy activator, were used in this study. AMPK inhibition down-regulated autophagy, abolished protection of melatonin, as indicated by significantly decreased cardiac function, increased inflammation and damaged mitochondrial function. Furthermore, autophagy inhibition by 3-MA significantly impaired the protective effects of melatonin, whereas autophagy activation by Rapa reversed LPS + Compound C induced myocardial injury. In addition, in vitro studies further confirmed the protection of melatonin against LPS-induced myocardial injury and the mechanisms involving AMPK-mediated autophagy signaling. Conclusions: In summary, our results demonstrated that melatonin protects against LPS-induced septic myocardial injury by activating AMPK mediated autophagy pathway.

5.
Environ Sci Technol ; 54(7): 3849-3860, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32131584

RESUMO

Secondary organic aerosol (SOA) constitutes a large fraction of organic aerosol worldwide, however, the formation mechanisms in polluted environments remain poorly understood. Here we observed fast daytime growth of oxygenated organic aerosol (OOA) (with formation rates up to 10 µg m-3 h-1) during low relative humidity (RH, daytime average 38 ± 19%), high RH (53 ± 19%), and fog periods (77 ± 13%, fog occurring during nighttime with RH reaching 100%). Evidence showed that photochemical aqueous-phase SOA (aqSOA) formation dominantly contributed to daytime OOA formation during the periods with nighttime fog, while both photochemical aqSOA and gas-phase SOA (gasSOA) formation were important during other periods with the former contributing more under high RH and the latter under low RH conditions, respectively. Compared to daytime photochemical aqSOA production, dark aqSOA formation was only observed during the fog period and contributed negligibly to the increase in OOA concentrations due to fog scavenging processes. The rapid daytime aging, as indicated by the rapid decrease in m,p-xylene/ethylbenzene ratios, promoted the daytime formation of precursors for aqSOA formation, e.g., carbonyls such as methylglyoxal. Photooxidants related to aqSOA formation such as OH radical and H2O2 also bear fast daytime growth features even under low solar radiative conditions. The simultaneous increases in ultraviolet radiation, photooxidant, and aqSOA precursor levels worked together to promote the daytime photochemical aqSOA formation. We also found that biomass burning emissions can promote photochemical aqSOA formation by adding to the levels of aqueous-phase photooxidants and aqSOA precursors. Therefore, future mitigation of air pollution in a polluted environment would benefit from stricter control on biomass burning especially under high RH conditions.


Assuntos
Poluentes Atmosféricos , Aerossóis , China , Peróxido de Hidrogênio , Raios Ultravioleta
6.
Environ Sci Pollut Res Int ; 27(15): 18602-18614, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32198692

RESUMO

This paper probes the nexus between solar energy technology, carbon intensity of energy structures, economic expansion, and carbon emissions (CO2) throughout 1990-2017 in China. The study utilized the vector auto-regressive (VAR) approach to co-integration testing and vector error-correction models to identify the most effective method for reducing CO2 emissions. Results from the Granger causality (GC) suggest a unidirectional causality between the variables. The test of impulse response function (IRF) constituted in the VAR technique was also applied in this study. The results indicate that energy structure intensity and economic expansion positively affect carbon emissions, while solar energy technology negatively affects carbon emissions. Simultaneous IRF analysis demonstrated that solar energy technology, energy structure carbon intensity, and economic expansion all have long-term effects on carbon emissions. The study concluded that when the economy expands, it influences CO2 emissions. Also, there exists a positive impact on CO2 emissions from the number of solar patents, but was seen to be decreasing gradually. The policy implications were also stated.


Assuntos
Desenvolvimento Econômico , Energia Solar , Carbono , Dióxido de Carbono/análise , China , Ecossistema
7.
Cells ; 9(2)2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32102444

RESUMO

Ubiquinone is an important cofactor that plays vital and diverse roles in many biological processes. Ubiquinone-binding proteins (UBPs) are receptor proteins that dock with ubiquinones. Analyzing and identifying UBPs via a computational approach will provide insights into the pathways associated with ubiquinones. In this work, we were the first to propose a UBPs predictor (UBPs-Pred). The optimal feature subset selected from three categories of sequence-derived features was fed into the extreme gradient boosting (XGBoost) classifier, and the parameters of XGBoost were tuned by multi-objective particle swarm optimization (MOPSO). The experimental results over the independent validation demonstrated considerable prediction performance with a Matthews correlation coefficient (MCC) of 0.517. After that, we analyzed the UBPs using bioinformatics methods, including the statistics of the binding domain motifs and protein distribution, as well as an enrichment analysis of the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32086219

RESUMO

Detection and diagnosis of cancer are especially essential for early prevention and effective treatments. Many studies have been proposed to tackle the subtype diagnosis problems with those data, which often suffer from low diagnostic ability and bad generalization. This paper studies a multiobjective PSO-based hybrid algorithm (MOPSOHA) to optimize four objectives including the number of features, the accuracy, and two entropy-based measures: the relevance and the redundancy simultaneously, diagnosing the cancer data with high classification power and robustness. First, we propose a novel binary encoding strategy to choose informative gene subsets to optimize those objective functions. Second, a mutation operator is designed to enhance the exploration capability of the swarm. Finally, a local search method based on the ''best/1'' mutation operator of differential evolutionary algorithm (DE) is employed to exploit the neighborhood area with sparse high-quality solutions since the base vector always approaches to some good promising areas. In order to demonstrate the effectiveness of MOPSOHA, it is tested on 41 cancer datasets including thirty-five cancer gene expression datasets and six independent disease datasets. Compared MOPSOHA with other state-of-the-art algorithms, the performance of MOPSOHA is superior to other algorithms in most of the benchmark datasets.

9.
Integr Zool ; 15(4): 314-328, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31912651

RESUMO

In this study, the lateral line systems in Chinese cavefish eyeless Sinocyclocheilus tianlinensis and eyed Sinocyclocheilus macrophthalmus were investigated to reveal their morphological changes to survive in harsh environments. Compared with the eyed cavefish S. macrophthalmus (atypical), the lateral line system in the eyeless cavefish S. tianlinensis (typical) has certain features to adapt to the dark cave environments: the superficial lateral line system in the eyeless species possesses a higher number of superficial neuromasts and more hair cells within an individual neuromast, and the trunk lateral line canal system in S. tianlinensis exhibits larger canal pores, higher canal diameter and more pronounced constrictions. Fluid-structure interaction analysis suggested that the trunk lateral line canal system in the eyeless S. tianlinensis should be more sensitive than that in the eyed S. macrophthalmus. These morphological features of the lateral line system in the eyeless S. tianlinensis probably enhance the functioning of the lateral line system and compensate for the lack of eyes. The revelation of the form-function relationship in the cavefish lateral line system provides inspiration for the design of sensitive artificial flow sensors.

10.
Phys Chem Chem Phys ; 22(2): 734-739, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31832632

RESUMO

ZSM-5 zeolites attract considerable attention owing to their wide range of applications in catalysis and separation. The crystals that are synthesized with tetrapropylammonium ions (TPA+) as the template show aluminum-zoning, i.e. aluminum being concentrated in the rim part of the crystal. Here, we study the aluminum distribution within individual crystals as a function of synthesis time and find that the degree of aluminum-zoning evolves. Crystals with inhomogeneous aluminum distribution persist since their emergence from the early stages of hydrothermal treatment. The degree of aluminum-zoning in the crystals increases with the synthesis time, accompanied by an increase in the crystal size and subsequently the formation of a well-defined crystal morphology. This indicates a gradual aluminum migration toward the crystal surface during the course of crystallization. Moreover, the addition of high-aluminum-containing species to the existing crystals preferentially takes place at the late stages of synthesis, which contributes to the inhomogeneous aluminum distribution within a crystal. As a result, the finally formed crystals have not only the largest crystal size but also the highest degree of aluminum-zoning. The insight into the origin of aluminum-zoning that our work provides advances our understanding of the relationship between aluminum distribution in zeolites and the synthesis time to design better catalysts.

11.
Sci Total Environ ; 707: 136083, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31863975

RESUMO

The characteristics of benzene, toluene, ethylbenzene, and xylene (BTEX) concentrations, their temporal and spatial variations, and their source origins from September-December 2017 at an urban and a background site in Beijing, China were investigated. The averaged (±σ) total mixing ratios of benzene, toluene, ethylbenzene, m, p-xylenes, and o-xylene were 0.40 ± 0.39 ppbv, 0.31 ± 0.34 ppbv, 0.08 ± 0.07 ppbv, 0.08 ± 0.08 ppbv, and 0.05 ± 0.05 ppbv at the SDZ site, which were 63%, 79%, 83%, 85%, and 89% lower than those at the Chinese Academy of Meteorological Sciences site (CMA). It is worth noting that the average mixing ratios of BTEX at SDZ and CMA were 0.86 ± 1.03 ppbv and 3.38 ± 2.80 ppbv during the heating period (HP), which were 2.3% and 21.9% lower than those before the HP, a decrease that was mainly related to the frequent occurrence of strong northerly and northwesterly winds and low relative humidity (RH) during the HP. Obvious differences were also observed between the BTEX composition proportions at the SDZ and CMA sites. On average, benzene comprised 44% of the total BTEX at SDZ, whereas toluene was the largest contributor to the total BTEX at CMA, accounting for 37%. In addition, the contributions of C8 aromatics (the sum of ethylbenzene, m, p-xylenes, and o-xylene) at CMA (36%) were also higher than those at SDZ (21%), reflecting the different emission sources of the two sites. In addition, the BTEX species showed similar and pronounced diurnal profiles at SDZ and CMA, all characterized by much higher values at night than during the day. Diagnostic ratios and source implications suggested that SDZ was affected mainly by biomass/biofuel/coal burning, with substantially elevated benzene levels during the winter HP, whereas CMA was affected both by traffic-related emissions and biomass/biofuel/coal burning emissions. These findings suggest the necessity of regionally-tailored control strategies both to reduce BTEX levels and to mitigate their environmental impact. Further analysis of the backward trajectories revealed that the BTEX compounds varied greatly in terms of air mass origins, but generally exhibited high values for slow air masses passing over areas south of Beijing, with dominant contributions from benzene, toluene, and m, p-xylenes.

12.
Sensors (Basel) ; 19(24)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817605

RESUMO

Fish and some amphibians can perform a variety of behaviors in confined and harsh environments by employing an extraordinary mechanosensory organ, the lateral line system (LLS). Inspired by the form-function of the LLS, a hydrodynamic artificial velocity sensor (HAVS) was presented in this paper. The sensors featured a polarized poly (vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)]/barium titanate (BTO) electrospinning nanofiber mat as the sensing layer, a polyimide (PI) film with arrays of circular cavities as the substrate, and a poly(methyl methacrylate) (PMMA) pillar as the cilium. The P(VDF-TrFE)/BTO electrospinning nanofiber mat demonstrated enhanced crystallinity and piezoelectricity compared with the pure P(VDF-TrFE) nanofiber mat. A dipole source was employed to characterize the sensing performance of the fabricated HAVS. The HAVS achieved a velocity detection limit of 0.23 mm/s, superior to the conventional nanofiber mat-based flow sensor. In addition, directivity was feasible for the HAVS, which was in accordance with the simulation results. The proposed bio-inspired flexible lateral line sensor with hydrodynamic perception ability shows promising applications in underwater robotics for real-time flow analysis.

13.
Aging (Albany NY) ; 11(22): 10061-10073, 2019 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733141

RESUMO

Doxorubicin (DOX) is a widely used and potent anticancer agent, but DOX dose-dependently induced cardiotoxicity greatly limits its use in clinic. Pterostilbene, a natural analog of resveratrol, is a known antioxidant and exerts myocardial protection. The present study explored the action and detailed mechanism of pterostilbene on DOX-treated cardiomyocytes. We investigated the effects of pterostilbene on established acute DOX-induced cardiotoxicity models in both H9c2 cells treated with 1 µM DOX and C57BL/6 mice with DOX (20 mg/kg cumulative dose) exposure. Pterostilbene markedly alleviated the DOX exposure-induced acute myocardial injury. Both in vitro and in vivo studies revealed that pterostilbene inhibited the acute DOX exposure-caused oxidative stress and mitochondrial morphological disorder via the PGC1α upregulation through activating AMPK and via PGC1α deacetylation through enhancing SIRT1. However, these effects were partially reversed by knockdown of AMPK or SIRT1 in vitro and treatment of Compound C (AMPK inhibitor) or EX527 (SIRT1 inhibitor) in vivo. Our results indicate that pterostilbene protects cardiomyocytes from acute DOX exposure-induced oxidative stress and mitochondrial damage via PGC1α upregulation and deacetylation through activating AMPK and SIRT1 cascades.

14.
Aging (Albany NY) ; 11(18): 7948-7960, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562288

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is a heavy burden on cancer patients worldwide. This study aimed to evaluate the prevalence and influence of cardiovascular risk factors (CVRF) and CVD on the all-cause mortality among Chinese cancer patients. RESULTS: Overall, 13.0% of all cancer patients had at least one type of CVRFs and 5.0% with CVDs. Patients with CVRF or CVD presented more frequently at later stages and received higher percentage of oncotherapy. During 1,782,527 person-years of follow-up, the all-cause mortality in cancer patients with CVDs and with CVRFs was higher compared with those without (182.6/1000, 109.5/1000 and 93.3/1000 person-years, respectively). Cox regression analysis showed that patients with heart failure (HR 1.79, 95% CI 1.61-1.99), myocardial infarction (HR 1.50, 95% CI 1.16-1.95), atrial fibrillation (HR 1.30, 95% CI 1.09-1.53), stroke (HR 1.21, 95% CI 1.11-1.32), hypertension (HR 1.10, 95% CI 1.04-1.16) and diabetes (HR 1.16, 95% CI 1.08-1.24) had increased all-cause mortality, whereas dyslipidemia patients had better prognosis (HR 0.73, 95% CI 0.64-0.83). Stratified by cancer type, the prognostic impact of specific CVRF or CVD varied. METHODS: We consecutively recruited 710,170 cancer patients between Feb. 1995 and Jun. 2018. A stratified Cox proportional hazards model was used to analyze the effect of comorbidities on the overall survival of patients stratified by cancer type. CONCLUSIONS: Cancer patients are vulnerable to comorbidity related to heart and cerebral disease. The influence of comorbidities on prognosis is noticeable and specific both for the type of cancer and comorbidities.

15.
Materials (Basel) ; 12(19)2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31557933

RESUMO

Calcium sulphoaluminate cement (CSA) has the characteristics of quick hardening, high early strength and high impermeability, however its strength growth persistence in the middle and late stages (after the age of 3 days) is poor. In order to improve this disadvantage, the pilot production of alite (C3S) modified CSA (AMCSA) clinker was carried out by liquid phase manipulation and barium ion doping technology. The effects of different dosages of gypsum on the hydration and hardening properties of AMCSA, such as setting time, hydration rate, compressive strength and hydration products, were studied. The results show that the mineral content of ye'elimite, C2S, C3S and iron phase in the calcined AMCSA clinker are 48.5 wt.%, 32.6 wt.%, 11.7 wt.% and 7.2 wt.% respectively, which are close to the designed mineral composition. The stable coexistence of ye'elimite and C3S in the same clinker system is realized. The initial and final setting time of AMCSA are retarded with the increasing gypsum dosage. When the gypsum dosage is 15 wt.% under the experimental conditions in this study, the AMCSA mortar reaches the highest compressive strength at every age. The strength of AMCSA mortar at 28 days is still significantly improved compared with that at 3 days, which indicates that the shortcoming of the low strength growth persistence of CSA in the middle and late stages is improved.

16.
Bioinspir Biomim ; 14(6): 066004, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31434068

RESUMO

With the assistance of mechanosensory lateral line system, fish can perceive minute water motions in complex underwater environments. Inspired by the constriction within canal nearby canal neuromast in fish lateral line system, we proposed a novel canal artificial lateral line (CALL) device with constriction in canal nearby the sensing element. The designed CALL device consisted of a poly(vinylidene fluoride-trifluoroethylene)/polyimide cantilever as the sensing element and a polydimethylsiloxane (PDMS) microfluid canal. Two types of CALL devices, i.e., CALL with straight canal (S-CALL) and CALL with constriction canal (C-CALL), were developed and characterized employing a dipole source. Experimental results showed that the proposed C-CALL device achieved a pressure gradient detection limit of 0.64 Pa m-1, which was much lower than the S-CALL device. It indicates that the constriction in the canal nearby the sensing element could enhance the hydrodynamic pressure sensing performance of the CALL device. In addition, the constriction could modify the frequency response of the CALL device, and the C-CALL device achieved higher voltage output than S-CALL in high-frequency domain.


Assuntos
Biomimética/instrumentação , Peixes/fisiologia , Animais , Desenho de Equipamento , Hidrodinâmica , Sistema da Linha Lateral , Reologia/instrumentação
17.
Int J Nanomedicine ; 14: 5527-5540, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413561

RESUMO

Background: Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic. Purpose: In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) grafted folate (FA-PEG-b-PAsp) to obtain the block polymer folate polyethylene glycol-b-poly(asparaginyl-chidamide) (FA-PEG-b-PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice. Methods: Model photosensitizer pyropheophorbide-a (Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol-b-poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis. Results: With favorable and stable sphere morphology under transmission electron microscope (TEM) (~93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi. Conclusion: As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.


Assuntos
Aminopiridinas/química , Benzamidas/química , Ácido Fólico/uso terapêutico , Micelas , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofila/análogos & derivados , Clorofila/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Ácido Fólico/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/metabolismo
18.
Int J Biol Sci ; 15(8): 1637-1653, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360107

RESUMO

Butein, a member of the chalcone family, is a potent anticarcinogen against multiple cancers, but its specific anti-NSCLC mechanism remains unknown. The present study examined the effects of butein treatment on NSCLC cell lines and NSCLC xenografts. Butein markedly decreased NSCLC cell viability; inhibited cell adhesion, migration, invasion, and colony forming ability; and induced cell apoptosis and G2/M phase arrest in NSCLC cells. Moreover, butein significantly inhibited PC-9 xenograft growth. Both in vivo and in vitro studies verified that butein exerted anti-NSCLC effect through activating endoplasmic reticulum (ER) stress-dependent reactive oxygen species (ROS) generation. These pro-apoptotic effects were reversed by the use of 4- phenylbutyric acid (4-PBA), CHOP siRNA, N-acetyl-L-cysteine (NAC) and Z-VAD-FMK (z-VAD) in vitro. Moreover, inhibition of ER stress markedly reduced ROS generation. In addition, in vivo studies further confirmed that inhibition of ER stress or oxidative stress partially abolished the butein-induced inhibition of tumor growth. Therefore, butein is a potential therapeutic agent for NSCLC, and its anticarcinogenic action might be mediated by ER stress-dependent ROS generation and the apoptosis pathway.


Assuntos
Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Acetilcisteína/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Butilaminas/metabolismo , Adesão Celular/genética , Adesão Celular/fisiologia , Ciclo Celular/genética , Ciclo Celular/fisiologia , Movimento Celular/genética , Movimento Celular/fisiologia , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Estresse do Retículo Endoplasmático/genética , Estresse do Retículo Endoplasmático/fisiologia , Fator de Iniciação 2 em Eucariotos/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Potencial da Membrana Mitocondrial/genética , Potencial da Membrana Mitocondrial/fisiologia , Camundongos Nus , Estresse Oxidativo/genética , Transdução de Sinais/fisiologia , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-31277519

RESUMO

We observed significant effects of particulate matter (PM2.5) on cause-specific mortality by applying a time-stratified case-crossover and lag-structure designs in Beijing over a nine-year study period (2005-2013). The year-round odds ratio (OR) was 1.005 on the current day with a 10 µg/m3 increase in PM2.5 for all-cause mortality. For cardiovascular mortality and stroke, the ORs were 1.007 and 1.008 on the current day, respectively. Meanwhile, during a lag of six days, the cumulative effects of haze on relative risk of mortality, respiratory mortality and all-cause mortality was in the range of 2~11%. Moreover, we found a significant seasonal pattern in the associations for respiratory mortality: significant associations were observed in spring and fall, while for all-cause mortality, cardiovascular mortality, cardiac and stroke, significant associations were observed in winter. Moreover, increasing temperature would decrease risks of mortalities in winter taking fall as the reference season. We concluded that in summer, temperature acted as a direct enhancer of air pollutants; while in winter and spring, it was an index of the diameter distribution and composition of fine particles.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Mortalidade , Material Particulado/toxicidade , Estações do Ano , Poluentes Atmosféricos/química , Pequim , China , Monitoramento Ambiental , Humanos , Razão de Chances , Material Particulado/química , Projetos de Pesquisa , Fatores de Risco , Temperatura , Estudos de Tempo e Movimento
20.
Front Genet ; 10: 542, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244885

RESUMO

The early control and prevention of cancer contributes effectively interventions and cancer therapies. Secretory protein, one of the richest biomarkers, is proved important as molecular signposts of the physiological state of a cell. In this work, we aim to propose a proteomic high-throughput technology platform to facilitate detection of early cancer by means of biomarkers that secreted into the bloodstream. We compile a new benchmark dataset of human secretory proteins in plasma. A series of sequence-derived features, which have been proved involved in the structure and function of the secretory proteins, are collected to mathematically encode these proteins. Considering the influence of potential irrelevant or redundant features, we introduce discrete firefly optimization algorithm to perform feature selection. We evaluate and compare the proposed method SCRIP (Secretory proteins in plasma) with state-of-the-art approaches on benchmark datasets and independent testing datasets. SCRIP achieves the average AUC values of 0.876 and 0.844 in five-fold the cross-validation and independent test, respectively. Besides that, we also test SCRIP on proteins in four types of cancer tissues and successfully detect 66∼77% potential cancer biomarkers.

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