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1.
Nanoscale ; 11(44): 21493-21501, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31686063

RESUMO

Pressure-induced surface-enhanced Raman spectroscopy (PI-SERS) represents a new frontier in the research field of SERS. However, relatively few studies have focused on PI-SERS due to many difficulties, such as easy aggregation of nanoparticles, and difficulty in understanding the interaction mechanisms between probe molecules and the SERS substrate at high pressure. Here we developed an efficient semiconductor-metal SERS substrate (MoS2/Au) to study PI-SERS. Different from the previously reported monotonous decrease in Raman intensities upon compression, an anomalous Raman enhancement of R6G molecules adsorbed on the MoS2/Au substrate was observed up to 2.39 GPa, at which the degree of charge transfer (ρCT) between the R6G molecules and the MoS2/Au substrate reaches a maximum. By comparison, it is proposed that the decoration of Au on the SERS system could bring about a two-step charge transfer (CT) process, introduce localized surface plasmon resonance (LSPR), and thus favor the PI-SERS enhancement. Moreover, this charge transfer also causes obvious changes in the optical behaviors of R6G molecules upon compression. This brings new insights into the SERS study and also offers new ideas for the development of SERS application in high pressure studies.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31728796

RESUMO

Fearful temperament represents one of the most robust predictors of child and adolescent anxiety; however, not all children with fearful temperament unvaryingly develop anxiety. Diverse processes resulting from the interplay between automatic processing (i.e., attention bias) and controlled processing (i.e., effortful control) drive the trajectories toward more adaptive or maladaptive directions. In this review, we examine the associations between fearful temperament, attention bias, and anxiety, as well as the moderating effect of effortful control. Based on the reviewed literature, we propose a two-mechanism developmental model of attention bias that underlies the association between fearful temperament and anxiety. We propose that the sub-components of effortful control (i.e., attentional control and inhibitory control) play different roles depending on individuals' temperaments, initial automatic biases, and goal priorities. Our model may help resolve some of the mixed findings and conflicts in the current literature. It may also advance our knowledge regarding the cognitive mechanisms linking fearful temperament and anxiety, as well as facilitate the continuing efforts in identifying and intervening with children who are at risk. Finally, we conclude the review with a discussion on the existing limitations and then propose questions for future research.

3.
Inorg Chem ; 58(21): 14830-14841, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31638779

RESUMO

Y2MnGa(Mn4-xGax)O12 solid solutions were synthesized at high pressure of ∼6 GPa and high temperature of ∼1570 K for the 0 ≤ x ≤ 3 compositional range. Synchrotron X-ray and neutron powder diffraction were used to study the crystal structures and cation distributions. These solutions adopt the parent structure of the A-site columnar-ordered quadruple perovskite family with space group P42/nmc (No. 137). They have lattice parameters of a = 7.36095 Å and c = 7.753 84 Å (x = 0), a = 7.361 68 Å and c = 7.716 16 Å (x = 1), a = 7.360 34 Å and c = 7.67142 Å (x = 2), and a = 7.363 93 Å and c = 7.616 85 Å (x = 3) at room temperature. The x = 0 sample has a cation distribution of [Y3+2]A[Mn3+]A'[Ga3+0.68Mn2+0.32]A″[Mn3.68Ga0.32]BO12 with a preferred localization of Ga3+ in the tetrahedral A″ site and with a small amount of Ga3+ in the octahedral B site. A complete triple A-site order, [Y3+2]A[Mn3+]A'[Ga3+]A″[Mn3+4-xGa3+x]BO12, is realized for x ≥ 1. All samples demonstrate spin-glass-like magnetic properties, and the absence of a long-range magnetic order at the ground state at 1.5 K was confirmed by neutron diffraction for the x = 1 sample. First-principles calculations indicated the spin-glass-like magnetic ordering is derived from the Ga substitution to the B sites and gave evidence that the ideal cation distribution could produce robust ferromagnetism in this family of perovskites.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31659890

RESUMO

Two-dimensional heterojunctions exhibit many unique features in nanoelectronic and optoelectronic devices. However, heterojunction engineering requires a complicated alignment process and some defects are inevitably introduced during material preparation. In this work, a laser scanning technique is used to construct a lateral WSe2 p-n junction. The laser-scanned region shows p-type behavior, and the adjacent region is electrically n-doped with a proper gate voltage. The laser-oxidized product WOx is found to be responsible for this p-type doping. After laser scanning, WSe2 displays a change from ambipolar to unipolar p-type property. A significant photocurrent emerges at the p-n junction. Therefore, a self-powered WSe2 photodetector can be fabricated based on this junction, which presents a large photoswitching ratio of 106, a high photoresponsivity of 800 mA W-1, and a short photoresponse time with long-term stability and reproducibility. Therefore, this selective laser-doping method is prospective in future electronic applications.

5.
Proteins ; 87(12): 1200-1221, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31612567

RESUMO

We present the results for CAPRI Round 46, the third joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of 20 targets including 14 homo-oligomers and 6 heterocomplexes. Eight of the homo-oligomer targets and one heterodimer comprised proteins that could be readily modeled using templates from the Protein Data Bank, often available for the full assembly. The remaining 11 targets comprised 5 homodimers, 3 heterodimers, and two higher-order assemblies. These were more difficult to model, as their prediction mainly involved "ab-initio" docking of subunit models derived from distantly related templates. A total of ~30 CAPRI groups, including 9 automatic servers, submitted on average ~2000 models per target. About 17 groups participated in the CAPRI scoring rounds, offered for most targets, submitting ~170 models per target. The prediction performance, measured by the fraction of models of acceptable quality or higher submitted across all predictors groups, was very good to excellent for the nine easy targets. Poorer performance was achieved by predictors for the 11 difficult targets, with medium and high quality models submitted for only 3 of these targets. A similar performance "gap" was displayed by scorer groups, highlighting yet again the unmet challenge of modeling the conformational changes of the protein components that occur upon binding or that must be accounted for in template-based modeling. Our analysis also indicates that residues in binding interfaces were less well predicted in this set of targets than in previous Rounds, providing useful insights for directions of future improvements.

6.
Mol Med Rep ; 20(4): 3679-3690, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485671

RESUMO

Diffuse large B­cell lymphoma (DLBCL) is a common subtype of non­Hodgkin lymphoma, which is curable in the majority of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R­CHOP) immunochemotherapy. However, the therapeutic mechanism of R­CHOP has not been elucidated. The GSE32918 and GSE57611 datasets were retrieved from The Gene Expression Omnibus database. The differentially expressed genes (DEGs) associated with R­CHOP therapy were identified using limma. Combined with prognostic information in GSE32918, DEGs found to be significantly associated with prognosis were selected using univariate Cox regression analysis and a risk prediction model was constructed. Based on this model, the samples in the training set (GSE32918) were divided into high and low risk score groups according to the median risk score. A total of 801 DEGs were identified between the R­CHOP treated DLBCL and primary DLBCL samples, from this 116 prognosis­associated genes were selected. Using Cox proportional hazards model, an optimal combination of 12 genes [including calcium/calmodulin dependent protein kinase I (CAMK1), hippocalcin like 4 (HPCAL4) and ephrin A5 (EFNA5)] was selected, and the sample risk score prediction model was constructed and validated. The DEGs between high risk score and low risk score groups were significantly enriched in functions associated with 'response to DNA damage stimulus', and pathways including 'cytokine­cytokine receptor interaction' and 'cell cycle'. The optimal combination of the 12 genes, including CAMK1, HPCAL4 and EFNA5, was found to be useful in predicting the prognosis of patients with DLBCL after R­CHOP treatment. Therefore, these genes may be affected by R­CHOP in DLBCL.

7.
J Phys Chem Lett ; 10(18): 5634-5639, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31483663

RESUMO

Tuning electron-transfer (ET) rates from catalysts to substrates is important for modulating photocatalytic organic reactions. In this work, we have taken pyrene-based photocatalysts (Py's) for photocatalytic hydrodefluorination of polyfluoroarenes (FAs) as model systems and conducted a first-principles study on modulating ET rates from Py to FA via the chemical modification of Py with different electron-donating/withdrawing groups (EDGs/EWGs). The computed spatial distributions of frontier Kohn-Sham orbitals suggest that ET is energetically more favorable for Py-EDGs than for Py-EWGs. The estimated ET rates by a simplified Marcus model show that they are appreciably enhanced by EDG substitution and weakened by EWG substitution. Noticeably, the associated Gibbs free-energy change plays a dominant role. Our findings of tuning ET rates for Py-FA complexes via chemical group modifications cast new insight into the rational design of metal-free photocatalysts for organic transformations.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31535296

RESUMO

PURPOSE: Vulnerable plaque detection is important to acute coronary syndrome (ACS) diagnosis. In recent years, intravascular optical coherence tomography (IVOCT) imaging has been used for vulnerable plaque detection. Current automated detection methods adopt the traditional image classification and object detection algorithms, such as the logistic regression model, SVM, and Haar-Adaboost, to detect vulnerable plaques. The detection quality of these methods is relatively low. The aim of this study is to improve the detection quality of vulnerable plaque. METHODS: We propose an automatic detection system of vulnerable plaque for IVOCT images based on deep convolutional neural network (DCNN). The system is mainly composed of four modules: pre-processing, deep convolutional neural networks (DCNNs), post-processing, and ensemble. The IVOCT images input to DCNNs are firstly pre-processed by using the methods of de-noising and data augmentation. Then multiple DCNNs are used to detect the vulnerable plaques in the IVOCT images; the vulnerable plaque regions and their corresponding labels and scores are output. Next, the output results of each network are processed by the post-processing module. We propose three algorithms, union of intersecting regions, duplicated region processing, and small gaps removal for post-processing. Finally, the output detection results of multiple networks are combined using a proposed combining method in ensemble module. RESULTS: We evaluated the proposed method in a dataset of 300 IVOCT images. Experimental results show that our system can achieve a precision rate of 88.84%, a recall rate of 95.02%, and an overlap rate of 85.09%; the detection quality score is 88.46%. CONCLUSIONS: The proposed algorithms can detect vulnerable plaques with superior performance; our system can be used as an auxiliary diagnostic tool for vulnerable plaque detection in IVOCT images.

9.
J Cell Physiol ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541467

RESUMO

The long intergenic noncoding RNA, regulator of reprogramming (linc-ROR) has been reported to participate in tumorigenesis, while its functions and fundamental mechanisms in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, gain-of-function assays showed that linc-ROR upregulation enhanced cell viability, promoted cell proliferation, and inhibited apoptosis. Mechanistically, the regulatory network of linc-ROR/miR-204-5p/MDM2 was established with bioinformatics analysis and online databases, then validated via dual-luciferase reporter assays, RNA immunoprecipitation assays in ESCC cells. Linc-ROR positively regulates the expression of MDM2 as a molecular sponge of miR-204-5p. Moreover, results of western blot and coimmunoprecipitation indicated that linc-ROR overexpression enhanced the ubiquitination level of p53, and its downstream apoptosis-related genes have showed higher bcl-2 expression, lower bax, and cleaved caspase-3 expressions, while miR-204-5p could counteract with this effect. Finally, small interfering RNAs tailored to linc-ROR were established to further evaluate its effects on ESCC comprehensively. In summary, this study revealed that linc-ROR modulated cell apoptosis and regulated p53 ubiquitination via targeting miR-204-5p/MDM2 axis, which provides a novel therapeutic insight into treatments for ESCC.

10.
Brain Res ; 1723: 146378, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31425677

RESUMO

Cholesterol sulfate (CS) is one of the most important known sterol sulfates in human plasma and it is present as a normal constituent in a variety of human tissues. In both the brain and periphery, CS serves as a substrate for the synthesis of sulfonated adrenal steroids such as pregnenolone sulfate and dehydroepiandrosterone (DHEA) sulfate and as a constituent of many biological membranes including red blood cells where it functions as a stabilizing agent. It also acts as an endogenous regulator of cholesterol synthesis. However, the role of CS in brain metabolism and neurological disorder is unclear. In the current study we investigated the neuroprotective action of CS as well as its role in brain energy metabolism. The neuroprotective effect of CS and its role on cell metabolism were determined in primary astrocyte prepared from the cortex of postnatal day 0-2 C57BL/6 pups and a hippocampal HT-22 cell line using Calcein AM and MTT cell viability assay, flow cytometry, Seahorse extracellular flux analysis, and metabolism assay kits. We found that CS attenuates glutamate and rotenone induced cell death in HT-22 cells, decrease glutamate induced mitochondria membrane potential collapse, and reactive oxygen species production. Additionally, CS activates the Akt/Bcl2 pathway. We observed that CS impacts astrocyte metabolism by increasing mitochondrial phosphorylation, ATP, and glycogen contents. Our study demonstrated that CS modulates brain energy metabolism and its neuroprotective effects might be due to the activation of Akt signaling or its ability to decrease reactive oxygen species production.

11.
Colloids Surf B Biointerfaces ; 183: 110400, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31394421

RESUMO

A pesticide microcapsule was prepared by encapsulating avermectin (AVM) in a polyurea microcapsule via interfacial polymerization in acetic ether/water emulsion. The polyurea microcapsule was consisted of chitosan oligomer (CO) as the membrane material and diphenyl methane-4,4'-diisocyanate (MDI) as the crosslinker. A chemical modification was carried out by grafting a UV-absorbent, 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BTDA), to CO before interfacial polymerization to enhance the UV-resistance of the microcapsule. The BTDA grafted CO (CO-BTDA) and the AVM microcapsules were characterized by a variety of instrumental techniques, including NMR, FTIR, UV-vis, GPC-LS, DLS, SEM and TEM. The in vitro release test showed that the polyurea microcapsule maintained the sustained release of AVM for a longer period (up to 120 h) in comparison with the commercial AVM formulations (within 24 h). The photodegradation test revealed that the polyurea microcapsule significantly reduced the AVM degradation and extended the half-life of AVM from 4.16 h to 9.43 h. The AVM degradation was further reduced by using the BTDA-modified polyurea microcapsule. The corresponding half-life was extended up to 17.33 h and can be mediated by changing the mass ratio of BTDA: CO during the synthesis of CO-BTDA. The use of polyurea microcapsule did not raise a concern about pesticide residue as no AVM was detected after the photodegradation test. In addition, the polyurea microcapsule itself was subject to degradation under sunlight exposure, which reduced its residue in the environment.

13.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1126-1127: 121734, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31401450

RESUMO

Non-small cell lung cancer (NSCLC), as the most common histological type of lung cancer with high mortality rates, has been widely treated by Compound Kushen Injection (CKI) in China. Among various active components with many pharmacologic properties, matrine, oxymatrine, sophoridine, oxysophocarpine and N-methylcytisine, are the main bioactive alkaloids of CKI. Therefore, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously quantify the five alkaloids in nude rat plasma in this study. With aminopyrine as internal standard (IS), plasma samples were extracted by alkalified chloroform and then separated on an Agela Venusil MP C18 column (2.1 mm × 100 mm, 3 µm) using gradient elution. Water containing 10 mmol/L ammonium acetate (adjusted to pH 8.0 with ammonia water, A) and methanol (B) constituted the mobile phase system. Notably, the analysis was rapid and accurate due to a short running time of 6 min and a stereoisomer separation between matrine and sophoridine. Detection was implemented in MRM mode with an electrospray positive ionization source. Validation parameters were all in accordance with current criterion. The established method has been effectively employed to compare the pharmacokinetic behaviors of five alkaloids between normal and NSCLC nude rats. Results indicated that the pharmacokinetic behaviors of oxymatrine, sophoridine and N-methylcytisine from CKI could be changed when it was intravenously administrated to the NSCLC model rats, and possible reasons have been proposed. This study could provide meaningful reference for further clinical medication of CKI when combined with time-effect curve and clinical symptoms.

14.
Chemosphere ; 235: 288-296, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31260869

RESUMO

The Huai'an area in Jiangsu Province of East China is an endemic region of esophageal cancer (EC). The regional heterogeneity of EC suggests that the levels of potential carcinogens might vary throughout the environment. It has been suggested that the most likely carcinogens related to EC are a group known as the N-nitrosamines. In this study, we measured the concentrations of nine nitrosamines in drinking water and human urine in two areas in China, one with a high incidence of EC (Huai'an) and one with a low incidence (Nanjing). Among the nine target analytes, N-nitrosodi-n-propylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosopyrrolidine (NPyr), N-nitrosodiethylamine (NDEA) and N-nitrosomorpholine (NMor) occurred at higher concentrations in drinking water in the high incidence area. Inhabitants from the high incidence area also had urinary excretions with significantly higher concentrations of NDEA, NDBA, N-nitrosopiperidine (NPip) and N-nitrosodiphenylamine (NDPhA). These findings indicated that people in the high EC incidence area were exposed to higher levels of nitrosamines. However, the association between the incidence of EC and nitrosamines exposure will need to be evaluated in more detail.

15.
Clin Rheumatol ; 38(11): 3169-3178, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31302858

RESUMO

OBJECTIVE: This retrospective study evaluates lung abnormalities on high-resolution CT (HRCT) and clarifies which abnormality can predict the progressive fibrosis of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). OBJECTS AND METHODS: We identified 1096 RA patients, and enrolled 213 patients with a diagnosis of RA-ILD who underwent serial chest HRCT. Clinical data of the patients were obtained. The presence, extent, and distribution of lung abnormalities were assessed on CT scans. Logistic regression analysis was used to determine positive indicators with predictive value for progressive fibrosis, and 2 × 2 contingency tables were constructed to assess their diagnostic efficiency. RESULT: Of 213 RA-ILD patients, 106 (49.8%) were diagnosed as progressive fibrosis. The rates of advanced age, male, smoking history, shortness of breath, and anti-CCP antibody high titer positive were higher, and RA duration was shorter in progressive fibrosis patients. Reticular pattern (RP), peribronchovascular interstitium (PBVI) thickening, interlobular septal thickening, and traction bronchiolectasis were more common in the progressive fibrosis group (84.9% vs 42.1%, P < 0.001; 79.3% vs 45.8%, P < 0.001; 74.5% vs 43.9%, P < 0.001; 67.0% vs 40.2%, P < 0.001; respectively). Lung abnormalities demonstrated subpleural predominance, and the subpleural RP and/or interlobular septal thickening had a wide distribution in the progressive fibrosis group (71.7% vs 14.0%, P < 0.001). The overall extent of lung abnormalities was more extensive in the progressive fibrosis group (18.4% vs 14.2%, P < 0.05). Logistic regression analysis showed that a wide distribution of subpleural RP and/or interlobular septal thickening (OR, 18.15) and PBVI thickening (OR, 4.98) were independent risk factors predictive of progressive fibrosis. For the combination of these two CT abnormalities, sensitivity was 63.2%, specificity was 92.5%, positive likelihood ratio was 8.5, and negative likelihood ratio was 0.4 in predicting progressive fibrosis. CONCLUSIONS: A wide distribution of subpleural RP and/or interlobular septal thickening and PBVI thickening on HRCT appear predictive of progressive fibrosis in RA-ILD. The combined evaluation of these two CT abnormalities has a good judgment value. Key Points • We designed this study to investigate the risk factors for progressive fibrosis in patients with RA-ILD. Factors including clinical, physiological, radiological and therapeutic variables were all included in the data analysis. • Our results showed HRCT abnormalities, rather than other parameters, appeared predictive of progressive fibrosis in RA-ILD. • The methods and results of image evaluation in this article would provide reference to rheumatologists in identifying early stage of progressive fibrosis which helps to improve poor prognosis of RA-ILD.

16.
Lipids Health Dis ; 18(1): 131, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31153370

RESUMO

OBJECTIVE: Familial hypercholesterolemia (FH) is an important cause of premature coronary artery disease (CAD). Prognosis data are lacking in patients with FH and coronary artery disease particularly in the era of widespread statin use. We compared long-term prognosis between patients with and without FH after a coronary event. METHODS: In this retrospective study, 865 patients younger than 40 years of age with CAD were enrolled. FH was diagnosed based on the Dutch Lipid Clinic Network algorithm. Baseline characteristics, coronary angiographic findings and prognosis during median follow-up of 5 (3-8) years were compared between patients with or without FH. RESULTS: Definite or probable FH was detected in 37 patients (4.3%) and possible FH in 259 patients (29.9%). FH was associated with significantly higher prevalence of multi-vessel lesions (p < 0.001) and higher Gensini score (p = 0.008). In the subset of 706 patients for whom follow-up data were available, 127 (18.0%) suffered major adverse cardiovascular and cerebrovascular events (MACCE). FH was associated with increased risk of MACCE, independently of age, sex, smoking, body mass index, hypertension or diabetes mellitus (HR = 2.30, 95%CI = 1.09 to 4.84, p = 0.028). CONCLUSIONS: FH is an independent risk factor for MACCE in young patients after a coronary event during long-term follow-up. It is necessary to optimize lipid treatment of patients with FH after a coronary event.

17.
FASEB J ; 33(9): 10152-10164, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31184927

RESUMO

Endoplasmic reticulum (ER) stress is essential for brain ischemia/reperfusion (I/R) injury. However, whether it contributes to I/R-induced blood-brain barrier (BBB) injury remains unclear. cilostazol exerts protective effects toward I/R-induced BBB injury, with unclear mechanisms. This study explored the potential role of ER stress in I/R-induced endothelial cell damage and determined whether the therapeutic potential of cilostazol, with respect to I/R-induced endothelial cell damage, is related to inhibition of ER stress. We found that exposing brain endothelial cells (bEnd.3) to oxygen-glucose deprivation/reoxygenation (OGD/R) significantly activated ER stress and diminished the barrier function of cell monolayers; treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) or cilostazol prevented OGD/R-induced ER stress and preserved barrier function. Furthermore, OGD/R induced the expression and secretion of matrix metalloproteinase-9 and nuclear translocation of phosphorylated NF-κB. These changes were partially reversed by 4-PBA or cilostazol treatment. In vivo, 4-PBA or cilostazol significantly attenuated I/R-induced ER stress and ameliorated Evans blue leakage and tight junction loss. These results demonstrate that I/R-induced ER stress participates in BBB disruption. Targeting ER stress could be a useful strategy to protect the BBB from ischemic stroke, and cilostazol is a promising therapeutic agent for this process.-Nan, D., Jin, H., Deng, J., Yu, W., Liu, R., Sun, W., Huang, Y. Cilostazol ameliorates ischemia/reperfusion-induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress.

18.
Drug Des Devel Ther ; 13: 1107-1115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31040647

RESUMO

Background: With the development of drug delivery, novel tools and technological approaches have captured the attention of researchers in recent years. Several target drug delivery systems (DDSs) including nanoparticles (NPs) have been developed as an important strategy to deliver classical medicine. Objective: The objective of this study was to evaluate the application of novel daunorubicin (DNR)-loaded poly(lactic-co-glycolic acid)-poly-l-lysine-polyethylene glycol-transferrin (Tf) nanoparticles (DNR-loaded NPs) in hematologic malignancies in vitro and in vivo. Materials and methods: DNR-loaded NPs were prepared by the modified double-emulsion solvent evaporation/diffusion method, and its microscopic form was observed under scanning electron microscope. Intracellular distribution of DNR was directly detected by fluorescence microscopy. After establishment of a tumor xenograft model by injecting K562 cells into the left leg of nude mice, the therapeutic effect of the DNR-loaded NPs on the growth of tumors was measured by calculating the tumor size, and the relative expression of Caspase-3 protein was detected by immunohistochemical staining. Furthermore, intracellular concentration of DNR and the extent of cell apoptosis in primary leukemia cells were quantified by flow cytometry. Results: DNR-loaded NPs had a spherical shape of about 180 nm in diameter. DNR-loaded NP group showed a significant enhancement of cellular uptake in K562 cells compared with DNR group. Tumor inhibition rate was higher in DNR-loaded NP group in comparison with DNR group, and the relative expression of Caspase-3 protein was upregulated in DNR-loaded NP group compared with DNR group. Furthermore, DNR-loaded NPs obviously increased intracellular concentration of DNR in primary leukemia cells compared with DNR group, but there was no significant difference in primary cell apoptosis between the two groups. These findings suggest that the novel NP DDS can enhance the performance of conventional antitumor drugs and may be suitable for further application in the treatment of hematologic malignancies.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Daunorrubicina/farmacologia , Neoplasias Hematológicas/tratamento farmacológico , Nanopartículas/química , Poliésteres/química , Polilisina/análogos & derivados , Transferrina/química , Animais , Antibióticos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Daunorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias Hematológicas/patologia , Humanos , Células K562 , Camundongos , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Polilisina/química , Células Tumorais Cultivadas
19.
Biochem Biophys Res Commun ; 515(1): 92-98, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31128919

RESUMO

Angiogenesis plays a vital role in the process of embryo implantation, as it improves endometrial receptivity and guides embryo implantation, thus creating a favorable environment for subsequent development of the embryo. Hence, a theory of achieving contraception by inhibiting angiogenesis was put forward. Here, we screened the drugs inhibiting angiogenesis using cell scratch wound assay and a 3D biomimetic vascular microfluidic chip, then observed the effect of them on contraception by injecting these drugs into fertilized mice and observing if the embryos were implanted. We preliminarily verify the feasibility of contraception by inhibiting angiogenesis and gives a new direction in the development of contraceptive pills.

20.
Biosci Rep ; 39(6)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31101684

RESUMO

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Hydroxysteroid dehydrogenase like 2 (HSDL2) can regulate lipid metabolism and take part in cell proliferation. The purpose of the present study was to explore functional role of HSDL2 gene in PTC. The expression of HSDL2 protein in PTC tissues was estimated using immunohistochemistry analysis (IHC). HSDL2 mRNA level was detected through quantitative real-time polymerase chain reaction (qRT-PCR). Effects of HSDL2 gene on cell proliferation and apoptosis were assessed using the shRNA method for both in vitro and in vivo experiments. Potential target genes of HSDL2 were determined via bioinformatics analyses and Western blotting. HSDL2 was up-regulated in PTC tissues and cell lines compared with the controls (all P<0.05). Inhibiting HSDL expression could suppress PTC cell proliferation and cycle, and promote apoptosis in vitro. In vivo, the knockdown of HSDL2 gene could significantly suppress tumor growth (all P<0.05). Furthermore, AKT3, NFATc2 and PPP3CA genes might be potential targets of HSDL2 in PTC. HSDL2 expression was increased in PTC tissues and cells, which could promote tumor progression in vitro and in vivo.

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