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1.
J Zhejiang Univ Sci B ; 20(11): 868-876, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595723

RESUMO

Acrolein, known as one of the most common reactive carbonyl species, is a toxic small molecule affecting human health in daily life. This study is focused on the scavenging abilities and mechanism of ferulic acid and some other phenolic acids against acrolein. Among the 13 phenolic compounds investigated, ferulic acid was found to have the highest efficiency in scavenging acrolein under physiological conditions. Ferulic acid remained at (3.04±1.89)% and acrolein remained at (29.51±4.44)% after being incubated with each other for 24 h. The molecular mechanism of the detoxifying process was also studied. Detoxifying products, namely 2-methoxy-4-vinylphenol (product 21) and 5-(4-hydroxy-3-methoxyphenyl)pent-4-enal (product 22), were identified though nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS), after the scavenging process. Ferulic acid showed significant activity in scavenging acrolein under physiological conditions. This study indicates a new method for inhibiting damage from acrolein.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31583494

RESUMO

A Gram-stain negative, aerobic, non-flagellated, non-gliding, rod-shaped bacterium, designated strain YLY04T, was isolated from the gut microflora of a sea bass (Dicentrarchus labrax L.) collected from the coast of Yuanyao Wharf, Weihai, China. Growth was found to occur at pH 6.0-9.0 (optimum, 7.0-8.0), 4-37 °C (optimum, 28-30 °C) in the presence of 0-11.0% (w/v) NaCl (optimum, 3.0-4.0%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain YLY04T is closely related to Pelagivirga sediminicola BH-SD19T and Roseovarius antarcticus M-S13-148T. Strain YLY04T contains ubiquinone-10 as the sole respiratory quinone and summed feature 8 (C18:1ω7c and/or C18:1ω6c), cyclo-C19:0ω8c, C16:0 and 11-methyl-C18:1ω7c as the major fatty acids. The polar lipids of strain YLY04T were found to consist of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, an unidentified phospholipid and three unidentified lipids. The DNA G+C content was determined to be 62.7 mol%. The phenotypic, chemotaxonomic and phylogenetic properties, and genome analysis, indicated that strain YLY04T represents a novel species within the genus Pelagivirga, for which the name Pelagivirga dicentrarchi sp. nov. is proposed. The type strain is YLY04T (= MCCC 1H00334T = KCTC 62452T).

3.
ChemSusChem ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31589802

RESUMO

For the first time, graphene supported N-doped carbon (G@NC) with a high N-doping level was synthesized via in situ self-assembly of glucaminium-based ionic liquid (GIL) on pristine graphene under hydrothermal conditions. This two-dimensional metal-free nanohybrid exhibits much higher catalytic activity than most reported metal-free OER catalysts and even state-of-the-art Ir and Ru-based ones due to the high content of graphitic N greatly increasing the number of OER-active sites, the pristine graphene significantly promoting the OER activity of the C sites adjacent to the graphitic N, and N-doped graphitic carbon remarkably enhancing the charge transfer rate. This work not only creates a facile and economical approach to controllably fabricate pristine graphene supported carbon with a high N-doping level for the development of highly efficient metal-free OER catalysts, but also provides scientific insight into the mechanisms for both the in situ self-assembly and the high OER catalytic activity of G@NC.

4.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3672-3683, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602939

RESUMO

Sesquiterpenes are a class of terpenoids composed of three isoprene units( 15 carbons). Sesquiterpenoids possess a variety of different structures,including acyclic sesquiterpenes,monocyclic sesquiterpenoids,bicyclic sesquiterpenoids,tricyclic sesquiterpenoids,tetracyclic sesquiterpenoids and macrocyclic sesquiterpenoids. Among them,a large number of monocyclic sesquiterpenoids were isolated and display extensive bioactivities,such as cytotoxic,antioxidant,anti-inflammatory,antibacterial and other activities. In this review,we summarized the progress about the phytochemistry and biological activities of monocyclic sesquiterpenoids( a total of161 compounds) reported from 2014 to 2018( 5 years),including megastigmanes,monocyclofarnesol-type,bisabolane-type,germacrane-type,and other types of monocyclic sesquiterpenoids. Furthermore,several future research perspectives and development of sesquiterpenoids as potential therapeutic agents were discussed as well.

5.
Blood Adv ; 3(19): 2883-2894, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31585952

RESUMO

We developed an in vivo hematopoietic stem cell (HSC) transduction approach that involves HSC mobilization from the bone marrow into the peripheral bloodstream and the IV injection of an integrating, helper-dependent adenovirus (HDAd5/35++) vector system. HDAd5/35++ vectors target human CD46, a receptor that is abundantly expressed on primitive HSCs. Transgene integration is achieved by a hyperactive Sleeping Beauty transposase (SB100x) and transgene marking in peripheral blood cells can be increased by in vivo selection. Here we directed transgene expression to HSC-derived erythroid cells using ß-globin regulatory elements. We hypothesized that the abundance and systemic distribution of erythroid cells can be harnessed for high-level production of therapeutic proteins. We first demonstrated that our approach allowed for sustained, erythroid-lineage specific GFP expression and accumulation of GFP protein in erythrocytes. Furthermore, after in vivo HSC transduction/selection in hCD46-transgenic mice, we demonstrated stable supraphysiological plasma concentrations of a bioengineered human factor VIII, termed ET3. High-level ET3 production in erythroid cells did not affect erythropoiesis. A phenotypic correction of bleeding was observed after in vivo HSC transduction of hCD46+/+/F8-/- hemophilia A mice despite high plasma anti-ET3 antibody titers. This suggests that ET3 levels were high enough to provide sufficient noninhibited ET3 systemically and/or locally (in blood clots) to control bleeding. In addition to its relevance for hemophilia A gene therapy, our approach has implications for the therapy of other inherited or acquired diseases that require high levels of therapeutic proteins in the blood circulation.

6.
Pharmacology ; : 1-7, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31587003

RESUMO

INTRODUCTION: Cynaroside is a biological component isolated from Lonicera japonica Thunb, and it possesses numerous pharmacological activities. However, whether cynaroside affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. The purpose of this study was to investigate the effects of cynaroside on 8 major CYP isoforms in human liver microsomes (HLMs). METHODS: In this study, the inhibitory effects of cynaroside on the 8 human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using HLMs. RESULTS: The results showed that cynaroside inhibited the activity of CYP1A2, 3A4, and 2C9, with IC50 values of 21.74, 15.88, and 16.58 µmol/L, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that cynaroside was not only a noncompetitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP1A2 and 2C9, with Ki values of 7.33, 11.60, and 8.09 µmol/L, respectively. In addition, cynaroside is a time-dependent inhibitor for CYP3A4 with Kinact/KI value of 0.049/11.62 µmol/L-1min-1. CONCLUSION: The in vitro studies of cynaroside with CYP isoforms indicate that cynaroside has the potential to cause pharmacokinetic drug interactions with other coadministered drugs metabolized by CYP1A2, 3A4, and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.

7.
J Asian Nat Prod Res ; : 1-7, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31588784

RESUMO

Phytochemical investigation of 95% ethanol extract of the fruit of Forsythia suspensa resulted in the isolation of two new furofuran lignan glycoside derivatives pinoresinoside A (1) and phillyrigeninside A (2), along with three known ones. Their structures were established based on extensive spectroscopic data analyses and comparison with literature data. Absolute configuration of 1 was determined by CD method. In addition, compounds 1 and 2 were revealed to show in vitro cytotoxicity against human tumor cell lines (SGC-7901, MCF-7 and HepG2), with IC50 values ranging from 16.77 to 37.35 µM.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31518449

RESUMO

BACKGROUND AND AIM: The effect of real-time analysis of needle-based confocal laser endomicroscopy (nCLE) for gastric subepithelial lesions (SELs) on the diagnostic value is unclear. The study aimed to investigate the diagnostic efficacy of real-time nCLE for gastric SELs and to assess the technical aspects and safety of real-time nCLE. METHODS: Consecutive patients with gastric SELs ≥ 1 cm were prospectively investigated by endoscopic ultrasound (EUS), followed by nCLE. During EUS-nCLE, real-time nCLE diagnosis was made by an expert endoscopist. The procedure-relative adverse events were assessed and recorded. One-month wash-out period later, nCLE videos were reviewed off-line by the same endoscopist. The nCLE diagnoses were compared with corresponding pathological results. Additionally, image quality and interobserver agreements for the criteria were evaluated by three experienced endomicroscopists. RESULTS: Except for one failing to be punctured, 60 patients completed EUS-nCLE procedures successfully. Real-time nCLE had high diagnostic accuracies of ≥ 88.3% for gastric SELs. There were no significant differences between real-time and off-line nCLE diagnoses for gastric SELs (P > 0.05). The overall accuracy of real-time nCLE for diagnosis of gastric SELs was 86.7%. There were no procedure-relative adverse events occurred. In addition, the mean image quality score was 3.6 (1 = poor and 5 = excellent). The interobserver agreement was "almost perfect" for ectopic pancreas and "substantial" for gastrointestinal stromal tumor, leiomyoma and carcinoma. CONCLUSIONS: EUS-nCLE could provide in vivo real-time diagnostic imaging with a high diagnostic accuracy. Meanwhile, real-time nCLE was feasible and had a satisfactory safety profile.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31519007

RESUMO

As the three-dimensional analogs of graphene, Weyl semimetals display signatures of chiral anomaly which arises from charge pumping between the lowest chiral Landau levels of the Weyl nodes in the presence of parallel electric and magnetic fields. In this work, we study the pseudo chiral anomaly and its transport signatures in graphene ribbon with zigzag edges. Here "pseudo" refers to the case where the inverse of width of zigzag graphene ribbon plays the same role as magnetic field in three-dimensional Weyl semimetals. The valley chiral bands in zigzag graphene ribbons can be introduced by edge potentials, giving rise to the nonconservation of chiral current, i.e., pseudo chiral anomaly, in the presence of a longitudinal electric field. Further numerical results reveal that pseudo magnetoconductivity of zigzag graphene ribbons is positive and has a nearly quadratic dependence on the pseudofield, which is regarded as the transport signature of pseudo chiral anomaly.

11.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 894-897, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31506149

RESUMO

OBJECTIVE: To investigate the serum level of soluble transferrin receptor (sTfR) and its association with the degree of anemia in children with hemoglobin H (HbH) disease. METHODS: A total of 55 children with HbH disease were enrolled as the HbH group, and 30 healthy children were enrolled as the control group. The HbH group was further divided into a deletional HbH disease group and a non-deletional HbH disease group. A retrospective analysis was performed for hematological parameters and serum sTfR level in all groups. RESULTS: Of the 55 children with HbH disease, 39 had deletional HbH disease and 16 had non-deletional HbH disease. Compared with the control group, the deletional and non-deletional HbH disease groups had significantly lower hemoglobin (Hb), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) and a significantly higher serum level of sTfR. Compared with the deletional HbH disease group, the non-deletional HbH disease group had significantly lower red blood cell count (RBC) and Hb level and significantly higher MCV, MCH, and serum sTfR level. In children with HbH disease, serum sTfR level was negatively correlated with RBC and Hb level (r=-0.739 and -0.667 respectively, P<0.05) and positively correlated with MCV and MCH (r=0.750 and 0.434 respectively, P<0.05). CONCLUSIONS: Serum sTfR level is associated the degree of anemia in children with HbH disease, and sTfR may be a target for the treatment of HbH disease.


Assuntos
Talassemia alfa , Criança , Contagem de Eritrócitos , Hemoglobina H , Humanos , Receptores da Transferrina , Estudos Retrospectivos
12.
Math Biosci Eng ; 16(5): 3367-3381, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31499618

RESUMO

Healthcare industry is one of the promising fields adopting the Internet of Things (IoT) solutions. In this paper, we study secret sharing mechanisms towards resolving privacy and security issues in IoT-based healthcare applications. In particular, we show how multiple sources are possible to share their data amongst a group of participants without revealing their own data to one another as well as the dealer. Only an authorised subset of participants is able to reconstruct the data. A collusion of fewer participants has no better chance of guessing the private data than a non-participant who has no shares at all. To realise this system, we introduce a novel research upon secret sharing in the encrypted domain. In modern healthcare industry, a patient's health Article often contains data acquired from various sensor nodes. In order to protect information privacy, the data from sensor nodes is encrypted at once and shared among a number of cloud servers of medical institutions via a gateway device. The complete health Article will be retrieved for diagnosis only if the number of presented shares meets the access policy. The retrieval procedure does not involve decryption and therefore the scheme is favourable in some time-sensitive circumstances such as a surgical emergency. We analyse the pros and cons of several possible solutions and develop practical secret sharing schemes for IoT- based healthcare systems.

13.
J Vis Exp ; (150)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31498306

RESUMO

Aberrant changes in endothelial phenotype and morphology are considered to be initial events in the pathogenesis of atherosclerosis. Direct observation of the intact endothelium will provide valuable information for understanding the cellular and molecular events in the dysfunctional endothelial cells. Here, we describe a modified en face immunofluorescence staining technique which enables scientists to obtain clear images of the intact endothelial surface and analyze the molecule expression patterns in situ. The method is simple and reliable for observing the entire endothelial monolayer at different sites of the aorta. This technique may be a promising tool for understanding the pathophysiology of atherosclerosis, especially at an early stage.

14.
Mol Ther ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31494053

RESUMO

Our goal is the development of in vivo hematopoietic stem cell (HSC) transduction technology with targeted integration. To achieve this, we modified helper-dependent HDAd5/35++ vectors to express a CRISPR/Cas9 specific to the "safe harbor" adeno-associated virus integration site 1 (AAVS1) locus and to provide a donor template for targeted integration through homology-dependent repair. We tested the HDAd-CRISPR + HDAd-donor vector system in AAVS1 transgenic mice using a standard ex vivo HSC gene therapy approach as well as a new in vivo HSC transduction approach that involves HSC mobilization and intravenous HDAd5/35++ injections. In both settings, the majority of treated mice had transgenes (GFP or human γ-globin) integrated into the AAVS1 locus. On average, >60% of peripheral blood cells expressed the transgene after in vivo selection with low-dose O6BG/bis-chloroethylnitrosourea (BCNU). Ex vivo and in vivo HSC transduction and selection studies with HDAd-CRISPR + HDAd-globin-donor resulted in stable γ-globin expression at levels that were significantly higher (>20% γ-globin of adult mouse globin) than those achieved in previous studies with a SB100x-transposase-based HDAd5/35++ system that mediates random integration. The ability to achieve therapeutically relevant transgene expression levels after in vivo HSC transduction and selection and targeted integration make our HDAd5/35++-based vector system a new tool in HSC gene therapy.

15.
Anal Chim Acta ; 1086: 46-54, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31561793

RESUMO

Fusion of spectral and spatial information has been proved to be an effective approach to improve model performance in near-infrared hyperspectral data analysis. Regardless, most of the existing spectral-spatial classification methods require fairly complex pipelines and exact selection of parameters, which mainly depend on the investigator's experience and the object under test. Convolutional neural network (CNN) is a powerful tool for representing complicated data and usually works with few "hand-engineering", making it an appropriate candidate for developing a general and automatic approach. In this paper, a two-branch convolutional neural network (2B-CNN) was developed for spectral-spatial classification and effective wavelengths (EWs) selection. The proposed network was evaluated by three classification data sets, including herbal medicine, coffee bean and strawberry. The results showed that the 2B-CNN obtained the best classification accuracies (96.72% in average) when compared with support vector machine (92.60% in average), one dimensional CNN (92.58% in average), and grey level co-occurrence matrix based support vector machine (93.83% in average). Furthermore, the learned weights of the two-dimensional branch in 2B-CNN were adopted as the indicator of EWs and compared with the successive projections algorithm. The 2B-CNN models built with wavelengths selected by the weight indicator achieved the best accuracies (96.02% in average) among all the examined EWs models. Different from the conventional EWs selection method, the proposed algorithm works without any additional retraining and has the ability to comprehensively consider the discriminative power in spectral domain and spatial domain.

16.
Thorac Cancer ; 10(10): 1993-1999, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31475791

RESUMO

BACKGROUND: This study compared the results of the application of two different chest tube management systems; a drainage ball with low negative pressure and the more commonly used chest tube with water-sealed bottle, after video-assisted thoracoscopic (VATS) lobectomy. METHODS: A total of 60 patients undergoing lobectomy were enrolled into this prospective open label randomized clinical trial and equally divided into two groups. The data collected in the trial included age, gender, forced expiratory volume in 1 second (FEV1), blood loss, operation time, drainage volume, drainage time, length of stay, postoperative pain score according to the Visual Analogue Scale (VAS) within 24 hours after surgery and chest tube removal. This study was registered at ClinicalTrials.gov (NCT03598296). RESULTS: The characteristics of the patients were similar in both groups. Group ball patients had a lower pain score (after operation: 3.47 ± 1.80 vs. 6.20 ± 1.56, P < 0.001; after removal of chest tube: 1.47 ± 1.28 vs. 3.00 ± 1.29, P < 0.001); less analgesic used (2.83 ± 2.09 times vs. 5.00 ± 3.24 times, P = 0.003); less drainage time (upper tube: 3.89 ± 1.63 days vs. 5.10 ± 2.02 days, P = 0.048; lower tube: upper lobe 4.84 ± 1.61 days vs. 5.90 ± 1.52 days, P = 0.041; lower lobe: 3.82 ± 1.08 days vs. 5.70 ± 2.63 days, P = 0.042) and shorter length of stay (5.40 ± 1.65 days vs. 6.37 ± 1.99 days, P = 0.045). All other related parameters were similar in both groups. CONCLUSIONS: For patients undergoing lobectomy, using a drainage ball with negative pressure could reduce hospitalization days and postoperative pain compared with the more commonly used chest tube with water-sealed bottle when a strict postoperative curative procedure was performed.

17.
J Hazard Mater ; 383: 121198, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31541955

RESUMO

In this study, we discovered and isolated a new genus Brevibacillus strain from effluent of dyeing and finishing factory containing highly toxic p-chloroanilines (PCA). Based on the morphological, physiological and biochemical characteristics, as well as 16S rDNA sequence, the strain was identified and denominated as Brevibacillus S-618. Co-metabolism effect was found with extra carbon sources including sodium succinate, sodium citrate, ammonium chloride and glucose which can efficiently promote the biodegradation process of PCA. Under the optimal growth conditions at temperature of 30 °C, pH˜7 and air-water ratio of 0.3 m3/m3·min, the degradation rate of PCA in a 2 L pilot bioreactor with high concentration of 180 mg/L increased from 86.7% to 100% within 72 h after adding sodium succinate. The release of chloride ions during the growth process of the strain was equivalent to the degradation amount of PCA. Meanwhile, the cleavage pathway of PCA degradation by Brevibacillus S-618 was proposed by analysis of enzyme activities of microorganism and intermediate products in the reaction. Benefiting from excellent degradation ability and unique characters in high pollutant contents, high efficient bioreactor can easily be scale up for industrial application. Our study provides a facile route for cost-effectively and environmental-friendly degrading hazardous chemicals.

18.
Cells ; 8(9)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546785

RESUMO

The Wnt/ß-catenin pathway plays a crucial role in development and renewal of the intestinal epithelium. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting ketogenic enzyme in the synthesis of ketone body ß-hydroxybutyrate (ßHB), contributes to the regulation of intestinal cell differentiation. Here, we have shown that HMGCS2 is a novel target of Wnt/ß-catenin/PPARγ signaling in intestinal epithelial cancer cell lines and normal intestinal organoids. Inhibition of the Wnt/ß-catenin pathway resulted in increased protein and mRNA expression of HMGCS2 and ßHB production in human colon cancer cell lines LS174T and Caco2. In addition, Wnt inhibition increased expression of PPARγ and its target genes, FABP2 and PLIN2, in these cells. Conversely, activation of Wnt/ß-catenin signaling decreased protein and mRNA levels of HMGCS2, ßHB production, and expression of PPARγ and its target genes in LS174T and Caco2 cells and mouse intestinal organoids. Moreover, inhibition of PPARγ reduced HMGCS2 expression and ßHB production, while activation of PPARγ increased HMGCS2 expression and ßHB synthesis. Furthermore, PPARγ bound the promoter of HMGCS2 and this binding was enhanced by ß-catenin knockdown. Finally, we showed that HMGCS2 inhibited, while Wnt/ß-catenin stimulated, glycolysis, which contributed to regulation of intestinal cell differentiation. Our results identified HMGCS2 as a downstream target of Wnt/ß-catenin/PPARγ signaling in intestinal epithelial cells. Moreover, our findings suggest that Wnt/ß-catenin/PPARγ signaling regulates intestinal cell differentiation, at least in part, through regulation of ketogenesis.

19.
PLoS One ; 14(9): e0222603, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31513669

RESUMO

OBJECTIVES: To examine the morbidities associated with workplace injury and to explore how clinical variables modify the risk of injury recurrence. METHODS: A case-control study was designed using Florida's statewide inpatient, outpatient, and emergency visits data obtained from the Healthcare Cost and Utilization Project. We included adults who were admitted for a workplace injury (WPI) or injury at other places (IOP), and a matched population of random controls without WPI/IOP. The associations between WPI and clinical morbidities were assessed by univariate and multivariable regression, ranking predictors by information gain, area under the receiver operating characteristic (AUROC), and odds ratios. We analyzed WPI recurrence using survival methods (Kaplan-Meier, Cox regression, survival decision trees) and developed prediction models via regularized logistic regression, random forest, and AdTree. Performance was assessed by 10-fold cross-validation comparing AUROC, sensitivity, specificity, and Harrell's c-index. RESULTS: A total of 80,712 WPI, 161,424 IOP, and 161,424 control patients were included; 485 distinct clinical diagnostic and 160 procedure codes were analyzed after filtering. Acute bronchitis and bronchiolitis, sprains and strains of shoulder and upper arm, ankle and foot, or other and unspecified parts of back, accidents caused by cutting and piercing instruments or objects, and overexertion and strenuous movements were identified as important consequences of WPI. The prediction models of injury recurrence identified several key factors, such as insurance type and prior injury events, although none of the models exhibited high predictive performance (best AUROC = 0.60, best c-index = 0.62). CONCLUSIONS: WPI is associated to diverse serious physical comorbidity burden. There are demographic, social and clinical comorbidity components associated to the risk of WPI recurrence, although their predictive value is moderate, which warrants future investigation in other information source domains, e.g. deepening into the environmental and societal sphere.

20.
Theranostics ; 9(21): 6314-6333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534553

RESUMO

Regenerated silk fibroin (SF) is a type of natural biomacromolecules with outstanding biocompatibility and biodegradability. However, stimulus-responsive SF-based nanocomplex has seldom been reported for application in tumor diagnosis and therapy. Methods: As a proof-of-concept study, a multifunctional SF@MnO2 nanoparticle-based platform was strategically synthesized using SF as a reductant and a template via a biomineralization-inspired crystallization process in an extremely facile way. Because of their mesoporous structure and abundant amino and carboxyl terminal residues, SF@MnO2 nanoparticles were co-loaded with a photodynamic agent indocyanine green (ICG) and a chemotherapeutic drug doxorubicin (DOX) to form a SF@MnO2/ICG/DOX (SMID) nanocomplex. Results: The obtained product was highly reactive with endogenous hydrogen peroxide (H2O2) in tumor microenvironment, which was decomposed into O2 to enhance tumor-specific photodynamic therapy (PDT). Moreover, SMID nanocomplex produced a strong and stable photothermal effect upon near-infrared (NIR) irradiation for photothermal therapy (PTT) owing to the distinct photothermal response of SF@MnO2 and stably conjugated ICG. The concurrent NIR fluorescence and magnetic resonance (MR) imaging in vivo both indicated effective tumor-specific enrichment of SMID nanoparticles via enhanced permeability and retention (EPR) effect. Animal studies further verified that SMID nanoparticles remarkably improved tumor inhibitive efficacy through combination PTT/PDT/chemotherapy with minimal systemic toxicity or adverse effect. Conclusion: This study demonstrated the promising potential of SF-based nanomaterial to address some of the key challenges in cancer therapy due to unfavorable tumor microenvironment for drug delivery.

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