Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 214
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
J Nanosci Nanotechnol ; 20(2): 673-679, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383062

RESUMO

A proper soft tissue seal between implants and gingiva is critical for success of dental implants. Implant surface modification is an important approach for achieving ideal host-implant integration. In this study, we used a new and simple oxidation method to generate a rough surface on implants at the nano scale, which oxidized titanium nano-foveolae (TiNF) surface. We further analyzed the surface topography and tested its effects on biological activities of human gingival fibroblasts. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) examination demonstrated that TiNF disks displayed uniform rough surfaces, with average TiNF diameters of approximately 60 nm and 100 nm respectively. However, the surfaces of smooth samples were highly irregular, and cell adhesion and proliferation rates on TiNF surfaces were significantly higher than those of the smooth surfaces. Extracellular matrix synthesis was also increased in the cells that interacted with oxidized TiNF surfaces. Altogether, these results suggest that the TiNF implant surfaces perform better for human gingival fibroblast biological activities compared to traditional smooth surfaces. Therefore, the TiNF implant surfaces may serve as ideal interface to facilitate implant-host integration.

2.
Sensors (Basel) ; 19(16)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412672

RESUMO

Optical remote sensing systems (RSSs) for monitoring vehicle emissions can be installed on any road and provide non-contact on-road measurements, that allow law enforcement departments to monitor emissions of a large number of on-road vehicles. Although many studies in different research fields have been performed using RSSs, there has been little research on the automatic recognition of on-road high-emitting vehicles. In general, high-emitting vehicles and low-emitting vehicles are classified by fixed emission concentration cut-points, that lack a strict scientific basis, and the actual cut-points are sensitive to environmental factors, such as wind speed and direction, outdoor temperature, relative humidity, atmospheric pressure, and so on. Besides this issue, single instantaneous monitoring results from RSSs are easily affected by systematic and random errors, leading to unreliable results. This paper proposes a method to solve the above problems. The automatic and fast-recognition method for on-road high-emitting vehicles (AFR-OHV) is the first application of machine learning, combined with big data analysis for remote sensing monitoring of on-road high-emitting vehicles. The method constructs adaptively updates a clustering database using real-time collections of emission datasets from an RSS. Then, new vehicles, that pass through the RSS, are recognized rapidly by the nearest neighbor classifier, which is guided by a real-time updated clustering database. Experimental results, based on real data, including the Davies-Bouldin Index (DBI) and Dunn Validity Index (DVI), show that AFR-OHV provides faster convergence speed and better performance. Furthermore, it is not easily disturbed by outliers. Our classifier obtains high scores for Precision (PRE), Recall (REC), the Receiver Operator Characteristic (ROC), and the Area Under the Curve (AUC). The rates of different classifications of excessive emissions and self-adaptive cut-points are calculated automatically in order to provide references for law enforcement departments to establish evaluation criterion for on-road high-emitting vehicles, detected by the RSS.

3.
J Food Biochem ; 43(7): e12862, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31353698

RESUMO

In this study, a novel method of continuous coupling of immobilized enzymatic hydrolysis reactor and membrane separation (CIEH-MS) was used to isolate the immunomodulatory peptides from type II collagen (CII) in chick sternal cartilage. The immobilized neutral protease was successfully prepared with an activity of 400.5 U/g. The CIEH-MS system loaded with immobilized neutral protease had high operational stability with enzyme decay constant of 0.0077 and half-life of 89.61 hr. Using a CIEH-MS system, the immunomodulatory peptides were obtained with lymphocyte proliferation of 66.23%, peptide yield of 23.43%, degree of hydrolysis (DH) of 22.41%, and permeate flux of 6.17 L/m2 h. The peptide fractions were further purified and the P3-2-4 fraction (RGQLGPM) with 760.4 Da molecular weights exhibited the highest lymphocyte proliferation activity (85.54%) and binding ability to human leukocyte antigen-DRB1 (HLA-DRB1) molecules (133.2 ng/ml). The results demonstrated that CIEH-MS system is an effective way to obtain immunomodulatory peptides from CII. PRACTICAL APPLICATIONS: Chick sternal cartilage is one of the by-products of meat processing, and it is often discarded as waste or used for low-value purposes. CII is the most abundant collagen in chick sternal cartilage, and recently studies have demonstrated that CII peptides possess the ability to induce immunologic tolerance for the treatment of chronic disease. In order to find potential applications for this by-product, immunomodulatory peptides from CII hydrolysates in chick sternal cartilage were isolated using a novel CIEH-MS system. The result showed that CII peptides exhibited a high immunomodulatory activity, and had a potential application in functional foods and medical fields.

4.
ACS Appl Mater Interfaces ; 11(28): 25524-25534, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31273980

RESUMO

Commercial hydrophobic poly(vinylidene fluoride) (PVDF) membranes are vulnerable to membrane fouling and pore wetting, hampering the use of membrane distillation (MD) for the treatment of surfactant- and oil-containing feed streams. To address these challenges, we designed novel Janus membranes with multilevel roughness to mitigate foulant adhesion and prevent pore wetting. Specifically, fouling- and wetting-resistant Janus MD membranes with hierarchically structured surfaces were tailored via a facile technique that involved oxidant-induced dopamine polymerization followed by in situ immobilization of silver nanoparticles (AgNPs) on commercial PVDF hollow fiber substrates. These membranes demonstrated outstanding antifouling properties and salt rejection performances in comparison to membranes with single-level structures. We ascribed the membranes' excellent performances to the coupled effects of improved surface hydrophilicity and self-healing mechanism brought about by AgNPs. Furthermore, the newly engineered membranes exhibited antibacterial properties in Bacillus acidicola solutions as evidenced by clear inhibition zones observed on a confocal laser scanning microscope. The development of hierarchically structured Janus MD membranes with multilevel roughness paves a way to mitigate membrane fouling and pore wetting caused by low-surface-tension feed streams in the MD process.

5.
J Gastroenterol ; 54(9): 804-818, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31037450

RESUMO

BACKGROUND: Ulcerative colitis (UC) is characterized by chronic inflammation in the colon and epigenetic factors underlying the occurrence. Circular RNAs (circRNAs) have been under intensive focus due to the circular construct and gene-regulating functions. However, the changes and roles of circRNAs in UC remain unknown. METHODS: Microarrays were used to detect the differentially expressed genes, and quantitative real-time PCR was used to identify the changes in UC. In silico analyses were performed to predict the functions of circRNAs and mRNAs. In vitro, epithelial cell lines were stimulated by pro-inflammation effectors to test the alterations in circRNAs. CircRNAs-microRNAs-mRNAs network clarified the potential mechanisms underlying circRNAs in UC. The binding site between hsa_circ_0007919 and miR-138 or let-7a was verified using dual-luciferase assay. RESULTS: A total of 264 significantly dysregulated circRNAs and 1869 differentially expressed mRNAs in inflamed mucosa were compared with the non-inflamed mucosa in UC. Hsa_circ_0004662 and hsa_circ_0007919 were altered largely in UC tissues. Hsa_circ_0007919 was reduced persistently after inflammatory treatments, and it was relevant to Mayo endoscopic subscores and the expression of tight junction molecules. Finally, hsa_circ_0007919 could harbor miR-138, and let-7a to regulate the targeted mRNAs EPC1 and VIPR1. CONCLUSIONS: Several circRNAs were differentially expressed in UC. Hsa_circ_0007919 is related to clinical characteristics and epithelial integrity by binding to hsa-let-7a, hsa-miR-138 to regulate the target genes. CircRNAs, especially hsa_circ_0007919, are associated with the pathogenesis and development of UC, with potential diagnostic and therapeutic implications.

6.
Int J Med Inform ; 126: 105-113, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31029251

RESUMO

BACKGROUND AND OBJECTIVE: The condition of vessel of the human eye is an important factor for the diagnosis of ophthalmological diseases. Vessel segmentation in fundus images is a challenging task due to complex vessel structure, the presence of similar structures such as microaneurysms and hemorrhages, micro-vessel with only one to several pixels wide, and requirements for finer results. METHODS: In this paper, we present a multi-scale deeply supervised network with short connections (BTS-DSN) for vessel segmentation. We used short connections to transfer semantic information between side-output layers. Bottom-top short connections pass low level semantic information to high level for refining results in high-level side-outputs, and top-bottom short connection passes much structural information to low level for reducing noises in low-level side-outputs. In addition, we employ cross-training to show that our model is suitable for real world fundus images. RESULTS: The proposed BTS-DSN has been verified on DRIVE, STARE and CHASE_DB1 datasets, and showed competitive performance over other state-of-the-art methods. Specially, with patch level input, the network achieved 0.7891/0.8212 sensitivity, 0.9804/0.9843 specificity, 0.9806/0.9859 AUC, and 0.8249/0.8421 F1-score on DRIVE and STARE, respectively. Moreover, our model behaves better than other methods in cross-training experiments. CONCLUSIONS: BTS-DSN achieves competitive performance in vessel segmentation task on three public datasets. It is suitable for vessel segmentation. The source code of our method is available at: https://github.com/guomugong/BTS-DSN.

7.
Cell Mol Biol Lett ; 24: 21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30915128

RESUMO

Melatonin receptors MT1 and MT2 (genes officially named MTNR1A and MTNR1B, respectively) play crucial roles in melatonin-mediated regulation of circadian rhythms, the immune system, and control of reproduction in seasonally breeding animals. In this study, immunolocalization assay showed that MT1 and MT2 are highly expressed in Leydig cell membrane. To understand the biological function of melatonin receptors in hCG-induced testosterone synthesis, we generated melatonin receptor knockdown cells using specific siRNA and performed testosterone detection after hCG treatment. We found that knockdown of melatonin receptors, especially MTNR1A, led to an obvious decrease (> 60%) of testosterone level. Our further study revealed that knockdown of melatonin receptors repressed expression, at both the mRNA level and the protein level, of key steroidogenic genes, such as p450scc, p450c17 and StAR, which are essential for testosterone synthesis. hCG triggered endoplasmic reticulum (ER) stress to regulate steroidogenic genes' expression and apoptosis. To further investigate the potential roles of melatonin receptors in hCG-induced regulation of ER stress and apoptosis, we examined expression of some crucial ER stress markers, including Grp78, Chop, ATF4, Xbp1, and IRE1. We found that inhibition of melatonin receptors increased hCG-induced expression of Grp78, Chop and ATF4, but not Xbp1 and IRE1, suggesting that hCG may modulate IRE1 signaling pathways in a melatonin receptor-dependent manner. In addition, our further data showed that knockdown of MTNR1A and MTNR1B promoted hCG-induced expression of apoptosis markers, including p53, caspase-3 and Bcl-2. These results suggested that the melatonin receptors MTNR1A and MTNR1B are essential to repress hCG-induced ER stress and cell apoptosis. Our studies demonstrated that the mammalian melatonin receptors MT1 and MT2 are involved in testosterone synthesis via mediating multiple cell pathways.


Assuntos
Gonadotropina Coriônica/farmacologia , Deleção de Genes , Células Intersticiais do Testículo/metabolismo , Receptor MT1 de Melatonina/metabolismo , Testosterona/metabolismo , Animais , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Masculino , Camundongos , RNA Interferente Pequeno/metabolismo , Esteroides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testosterona/biossíntese
8.
Biotechnol J ; 14(9): e1900003, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30925016

RESUMO

Phosphoserine aminotransferase (SerC) from Escherichia coli (E. coli) MG1655 is engineered to catalyze the deamination of homoserine to 4-hydroxy-2-ketobutyrate, a key reaction in producing 1,3-propanediol (1,3-PDO) from glucose in a novel glycerol-independent metabolic pathway. To this end, a computation-based rational approach is used to change the substrate specificity of SerC from l-phosphoserine to l-homoserine. In this approach, molecular dynamics simulations and virtual screening are combined to predict mutation sites. The enzyme activity of the best mutant, SerCR42W/R77W , is successfully improved by 4.2-fold in comparison to the wild type when l-homoserine is used as the substrate, while its activity toward the natural substrate l-phosphoserine is completely deactivated. To validate the effects of the mutant on 1,3-PDO production, the "homoserine to 1,3-PDO" pathway is constructed in E. coli by coexpression of SerCR42W/R77W with pyruvate decarboxylase and alcohol dehydrogenase. The resulting mutant strain achieves the production of 3.03 g L-1 1,3-PDO in fed-batch fermentation, which is 13-fold higher than the wild-type strain and represents an important step forward to realize the promise of the glycerol-independent synthetic pathway for 1,3-PDO production from glucose.

9.
Ann Thorac Surg ; 108(1): 219-226, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30885850

RESUMO

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can obtain a small amount of specimen. This study aims to evaluate the feasibility and robustness of using EBUS-EBNA samples to perform capture-based targeted next-generation sequencing (NGS). METHODS: Tissue samples from patients with advanced non-small cell lung cancer were collected by EBUS-TBNA and were formalin-fixed paraffin-embedded. Three representative genes, EGFR, ALK, and ROS1, were examined by amplification refractory mutation system polymerase chain reaction, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction. The remaining samples were processed with NGS assay with a 56-gene panel. Classic driver mutations detected by NGS were verified by conventional methods. RESULTS: Of the 85 samples from patients with advanced non-small cell lung cancer, 77 were performed successfully with all assays. Forty-one mutations in EGFR, ALK, and ROS1 were detected in both conventional methods and NGS, representing a 100% concordance. In contrast, four EGFR mutations detected by NGS were not covered in the targeted regions of amplification refractory mutation system polymerase chain reaction, leading to a negative call in these patients. Altogether, NGS detected 12 additional variants, including six KRAS mutations, one BRAF mutation, one RET fusion, one MET amplification concurrent with EGFR L858R, one KRAS amplification together with EGFR 19del, and one ERBB2 amplification. The mean number of needle passes per lymph node was 5.2 in samples successfully applied in all assays. CONCLUSIONS: NGS assay can be successfully conducted with limited tissue samples obtained from EBUS-TBNA. Compared with conventional methods, NGS assay provides more comprehensive information on genetic alterations in tumors, which greatly assists therapeutic decision making for advanced lung cancer.

10.
Cancer Lett ; 448: 117-127, 2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-30742939

RESUMO

Studies have shown that hypoxia can induce cytoskeletal injury and remodeling through the activation of the RhoA/ROCK signaling pathway by hypoxia-inducible factor-1α (HIF-1α). Our previous study confirmed that CAPZA1 can modulate EMT by regulating actin cytoskeleton remodeling. However, the relationship between HIF-1α and CAPZA1 has not been illustrated. Therefore, this study aimed to investigate the mechanism by which hypoxia induces the remodeling of the actin cytoskeleton by regulating CAPZA1 in hepatocellular carcinoma (HCC) cells. In the present study, we showed that the low expression of CAPZA1 promotes HCC cell invasion and migration in vitro and in vivo by regulating actin cytoskeleton remodeling to drive EMT. Furthermore, we found that the combination of PIP2 and CAPZA1 enables CAPZA1 to be released from the barbed end of F-actin, which in turn drives the remodeling of the actin cytoskeleton. Finally, we confirmed that hypoxia increases PIP2 levels and its binding to CAPZA1 in HCC cells via the HIF-1α/RhoA/ROCK1 pathway. Thus, CAPZA1 and PIP2 could be therapeutic targets to inhibit the invasion and migration promoted by hypoxia in HCC cells.

11.
Plant J ; 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30444296

RESUMO

Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asia countries. A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India and is still used for the treatment of infectious disease in China. A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide, neoandrographolide and their analogs; touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases. Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and Hi-C data. Gene annotation predicted 25,428 protein-coding genes. To decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate also was obtained, which enabled identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis. We further carried out functional characterization of pairs of classes I and II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds. In addition, a glycosyltransferase able to catalyze O-linked glucosylation of andrograpanin, yielding the major active product neoandrographolide, was identified as well. Thus, our results demonstrate the utility of the combined genomic and transcriptomic dataset generated here for investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata. This article is protected by copyright. All rights reserved.

12.
Clin Lung Cancer ; 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30341018

RESUMO

BACKGROUND: For oligometastatic lung adenocarcinoma patients with sensitive epidermal growth factor receptor (EGFR) mutations, the role of local consolidative therapy (LCT) remains debatable. The purpose of this study was to investigate the efficacy of LCT in oligometastatic lung adenocarcinoma patients. PATIENTS AND METHODS: We conducted a retrospective study to assess the effects of LCT on progression-free survival (PFS) and overall survival (OS). Patients with advanced-stage oligometastatic lung adenocarcinoma harboring sensitive mutation of epidermal growth factor receptor (EGFR) who received EGFR-tyrosine kinase inhibitor (TKI) or EGFR-TKI plus LCT were admitted to Shanghai Chest Hospital from January 2010 to December 2016. The PFS and OS of the 2 groups were accordingly analyzed. RESULTS: A total of 231 patients (143 patients who received LCT plus EGFR-TKI [combination group] and 88 patients who only received EGFR-TKI only [monotherapy group]) were included in this study. Median PFS was significantly longer in the combination group (15 months; 95% confidence interval [CI], 13.611-16.389) than in the monotherapy group (10 months; 95% CI, 8.936-11.064; hazard ratio = 0.610; 95% CI, 0.461, 0.807; P = .000). The median OS in the combination group was 34 months (95% CI, 27.889, 40.111) versus 21 months (95% CI, 18.445, 23.555) in the monotherapy group (hazard ratio = 0.593; 95% CI, 0.430-0.817; P = .001). CONCLUSION: LCT combined with TKIs therapy was a feasible method that significantly improved PFS and OS among oligometastatic lung adenocarcinoma patients with EGFR mutations, and it thus might be considered as an important medical treatment during clinical management.

13.
Opt Express ; 26(15): 19328-19340, 2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30114108

RESUMO

During the atmospheric detection process in open space, the excessive phase noise is introduced into the signal, due to the atmospheric turbulence, which causes the intensity and phase fluctuation. In the previous study, a spectral data processing method based on the co-frequency and dual-wave has been used to reduce the influence of the scintillation noise from the atmospheric turbulence in open space, while the influence of the phase noise remains to be solved. So the wavelength modulated signal is theoretically analyzed at first. On studying the relationship between the dual-waves in one cycle to eliminate the phase fluctuation and reduce the phase fluctuation caused by the atmospheric turbulence, a new method of the spectral phase correction for the open space atmospheric detection has been proposed. An atmospheric detection experiment on the phase correction in the open space based on co-frequency and dual-wave has been carried out. The results show that the maximum fluctuation of the spectral signal processed with this method is 1.06%, while the power spectral density fluctuation is suppressed below 50Hz, and the Allan analysis result is 8.8 × 10-8(1s). Compared with the traditional concentration inversion method using 2f-wavelength modulation and the classical light intensity elimination, the proposed phase correction method can effectively reduce the fluctuation of random noise caused by the short-term atmospheric turbulence and the laser flashing to improve the stability of the concentration measurement, which has practical engineering value.

14.
Lung Cancer ; 121: 54-60, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29858028

RESUMO

OBJECTIVES: Genetic profiles of primary and metastatic lung tumor have been investigated by previous studies. However, whether they can be replaced by each other to guide treatment remains controversial. Moreover, it is unclear that whether genetic profiles of plasma can reflect genetic divergence between primary and metastatic lesions. MATERIALS AND METHODS: In this prospective study, we collected 35 pairs of matched primary tumor tissue, metastatic lymph nodes and plasma from treatment-naïve patients with advanced non-squamous non-small cell lung cancer (NSCLC) and applied to capture-based sequencing using a panel consisting 56 NSCLC-related genes to interrogate the heterogeneity and similarity among the 3 sites. RESULTS: We observed 62.0% (67/108) by-variant concordance rate among primary tumor, metastatic lymph nodes and plasma as well as 76.4% (81/106) by-variant concordance rate between primary tumor and metastatic lymph nodes. When the analysis restricted to driver genes, we achieved 60.9% (28/46) and 77.3% (34/44) concordance, respectively. Furthermore, there is no statistically significant difference in progression-free survival (PFS) of 17 patients who used matched targeted therapy between patients having 100% concordance rate between primary tumor and metastatic lymph nodes and patients having partially matched mutational profiles. CONCLUSION: Collectively, our study revealed a similar genetic profile shared between primary tumor and metastatic lymph nodes. The limited discordance observed can be partially reflected by plasma. Sequencing results obtained from either site can be utilized for providing treatment guidance.

15.
Front Plant Sci ; 9: 782, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29946330

RESUMO

The chloroplast is a self-independent organelle and contains its own transcription and translation systems. The establishment of genetic systems is vital for normal plant growth and development. We isolated a rice zebra leaf 16 (zl16) mutant derived from rice cultivar 9311. The zl16 mutant showed chlorotic abnormalities in the transverse sectors of the young leaves of seedlings. The use of transmission electron microscopy (TEM) demonstrated that dramatic defects occurred in variegated zl16 leaves during the early development of a chloroplast. Map-based cloning revealed that ZL16 encodes a ß-hydroxyacyl-ACP dehydratase (HAD) involved in de novo fatty acid synthesis. Compared with the wild type, a missense mutation (Arg164Trp) in the zl16 mutant was identified, which significantly reduced enzymatic activity and altered the three-dimensional modeling structure of the putative protein. ZL16 was ubiquitously expressed in various plant organs, with a pronounced level in the young leaf. A subcellular localization experiment indicated that ZL16 was targeted in the chloroplast. Furthermore, we analyzed the expression of some nuclear genes involved in chloroplast development, and found they were altered in the zl16 mutant. RNA-Seq analysis indicated that some genes related to cell membrane constituents were downregulated in the mutant. An in vivo metabolic assay revealed that the total fatty acid content in the mutant was significantly decreased relative to the wild type. Our results indicate that HAD is essential for the development of chloroplasts by regulating the synthesis of fatty acids in rice.

16.
Biomaterials ; 177: 52-66, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29885586

RESUMO

BACKGROUND: Naïve decellularized liver scaffold (nDLS)-based tissue engineering has been impaired by the lack of a suitable extracellular matrix (ECM) to provide "active micro-environmental" support. AIM: The present study aimed to examine whether a novel, regenerative DLS (rDLS) with an active ECM improves primary hepatocyte survival and prevents thrombosis. METHODS: rDLS was obtained from a 30-55% partial hepatectomy that was maintained in vivo for 3-5 days and then perfused with detergent in vitro. Compared to nDLS generated from normal livers, rDLS possesses bioactive molecules due to the regenerative period in vivo. Primary mouse hepatocyte survival was evaluated by staining for Ki-67 and Trypan blue exclusion. Thrombosis was assessed by immunohistochemistry and ex vivo diluted whole-blood perfusion. Hemocompatibility was determined by near-infrared laser-Doppler flowmetry and heterotopic transplantation. RESULTS: After recellularization, rDLS contained more Ki-67-positive primary hepatocytes than nDLS. rDLS had a higher oxygen saturation and blood flow velocity and a lower expression of integrin αIIb and α4 than nDLS. Tumor necrosis factor-α, hepatocyte growth factor, interleukin-10, interleukin-6 and interleukin-1ß were highly expressed throughout the rDLS, whereas expression of collagen-I, collagen-IV and thrombopoietin were lower in rDLS than in nDLS. Improved blood vessel patency was observed in rDLS both in vitro and in vivo. The results in mice were confirmed in large animals (pigs). CONCLUSION: rDLS is an effective DLS with an "active microenvironment" that supports primary hepatocyte survival and promotes blood vessel patency. This is the first study to demonstrate a rDLS with a blood microvessel network that promotes hepatocyte survival and resists thrombosis.

17.
Cell Death Differ ; 25(12): 2118-2129, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29880857

RESUMO

p63 and c-Myc are key transcription factors controlling genes involved in the cell cycle and cellular senescence. We previously reported that p63α can destabilize MM1 protein to derepress c-Myc, resulting in cell cycle progress and tumorigenesis. However, how the proteasomal degradation of MM1 is facilitated remains unclear. In the present study, we identified a novel E3 ligase, HERC3, which can mediate ubiquitination of MM1 and promote its proteasome-dependent degradation. We found that ΔNp63α transcriptionally up-regulates HERC3 and knockdown of HERC3 abrogates ΔNp63α-induced down-regulation of MM1. Either overexpression of MM1 or ablation of HERC3 induces cell senescence, while knockdown of MM1 rescues cell senescence induced by deficiency of either ΔNp63α or HERC3, implicating the involvement of the ΔNp63α/HERC3/MM1/c-Myc axis in the modulation of cell senescence. Additionally, our Oncomine analysis indicates activation of the ΔNp63α/HERC3/MM1/c-Myc axis in invasive breast carcinoma. Together, our data illuminate a novel axis regulating cell senescence: ΔNp63α stimulates transcription of E3 ligase HERC3, which mediates ubiquitination of c-Myc modulator MM1 and targets it to proteasomal degradation; subsequently, c-Myc is derepressed by ΔNp63α, thereby cell senescence is modulated by this axis. Our work provides a new interpretation of crosstalk between p63 and c-Myc, and also sheds new light on ΔNp63α-controlled cell senescence and tumorigenesis.

18.
Int J Nanomedicine ; 13: 2477-2489, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719395

RESUMO

Background: Designer self-assembling peptide nanofibers (SAPNFs) as a novel kind of emerging nanomaterial have received more and more attention in the field of nanomedicine in recent years. However, a simple method to monitor and image SAPNFs is still currently absent. Methods: RADA16-I, a well-studied ionic complementary peptide was used as a model to check potential amyloid-like staining properties of SAPNFs. Thioflavin-T (ThT) and Congo red (CR) as specific dyes for amyloid-like fibrils were used to stain RADA16-I nanofibers in solution, combined with drugs or cells, or injected in vivo as hydrogels. Fluorescent spectrometry and fluorescent microscopy were used to check ThT-binding property, and polarized light microscopy was used to check CR-staining property. Results: ThT binding with the nanofibers showed enhanced and blue-shifted fluorescence, and specific apple-green birefringence could be observed after the nanofibers were stained with CR. Based on these properties we further showed that ThT-binding fluorescence intensity could be used to monitor the forming and changing of nanofibers in solution, while fluorescent microscopy and polarized light microscopy could be used to image the nanofibers as material for drug delivery, 3D cell culture, and tissue regeneration. Conclusion: Our results may provide convenient and reliable tools for detecting SAPNFs, which would be helpful for understanding their self-assembling process and exploring their applications.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Imagem Molecular/métodos , Nanofibras/química , Peptídeos/metabolismo , Amiloide/metabolismo , Animais , Corantes/metabolismo , Vermelho Congo/metabolismo , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Hidrogéis/química , Masculino , Microscopia de Fluorescência , Células PC12 , Peptídeos/química , Pirenos/administração & dosagem , Pirenos/química , Ratos , Ratos Sprague-Dawley , Espectrometria de Fluorescência , Coloração e Rotulagem/métodos , Tiazóis/metabolismo
19.
Nat Commun ; 9(1): 1813, 2018 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-29739938

RESUMO

Developing high-performance film dielectrics for capacitive energy storage has been a great challenge for modern electrical devices. Despite good results obtained in lead titanate-based dielectrics, lead-free alternatives are strongly desirable due to environmental concerns. Here we demonstrate that giant energy densities of ~70 J cm-3, together with high efficiency as well as excellent cycling and thermal stability, can be achieved in lead-free bismuth ferrite-strontium titanate solid-solution films through domain engineering. It is revealed that the incorporation of strontium titanate transforms the ferroelectric micro-domains of bismuth ferrite into highly-dynamic polar nano-regions, resulting in a ferroelectric to relaxor-ferroelectric transition with concurrently improved energy density and efficiency. Additionally, the introduction of strontium titanate greatly improves the electrical insulation and breakdown strength of the films by suppressing the formation of oxygen vacancies. This work opens up a feasible and propagable route, i.e., domain engineering, to systematically develop new lead-free dielectrics for energy storage.

20.
Ann Thorac Surg ; 106(4): 1251-1257, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29738756

RESUMO

BACKGROUND: In this study, we investigated the clinical significance of endobronchial ultrasound elastography for differentiating malignant and benign intrathoracic lymph nodes. METHODS: A meta-analysis was performed to evaluate the sensitivity and specificity of endobronchial ultrasound elastography in diagnosing intrathoracic lymph nodes. Publications before October 1, 2017, were included for analysis. Sensitivity, specificity, and other variables were pooled using the bivariate mixed-effects regression model. RESULTS: Seven studies met the inclusion criteria and were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio was 0.93 (95% confidence interval [CI], 0.85 to 0.97), 0.85 (95% CI, 0.78 to 0.90), 6.3 (95% CI, 4.2 to 9.2), 0.08 (95% CI, 0.04 to 0.18), and 74 (95% CI, 33 to 168), respectively. The summary receiver operating characteristic curve was 0.93 (95% CI, 0.91 to 0.95). CONCLUSIONS: The results revealed endobronchial ultrasound elastography is a new technique with high sensitivity and specificity. It has a fine performance in diagnosing intrathoracic lymph nodes.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA