Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 84
Filtrar
1.
Biomed Mater ; 17(1)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34736242

RESUMO

This study aims to construct a composite system of the tri-block polyethylene glycol injectable hydrogel (3B-PEG IH) and neural epithelial growth factor-like protein 1 (Nell-1), and to analyze its therapeutic effect on temporomandibular joint osteoarthritis (TMJOA). Sol-gel transition temperature was measured via inverting test. The viscoelastic modulus curves was measured by rheometer. Degradation and controlled release profiles of 3B-PEG IH were drawnin vitro.In vivogel retention and biocompatibility were completed subcutaneously on the back of rats. After primary chondrocytes were extracted and identified, the cell viability in 3B-PEG IH was measured. Evaluation of gene expression in hydrogel was performed by real-time polymerase chain reaction. TMJOA rabbits were established by intra-articular injection of type II collagenase. Six weeks after composite systems being injected, gross morphological score, micro-CT, histological staining and grading were evaluated. The rusults showed that different types of 3B-PEG IH all reached a stable gel state at 37 °C and could support the three-dimensional growth of chondrocytes, but poly(lactide-co-caprolactone)-block-poly(ethyleneglycol)-block-poly(lactide-co-caprolactone) (PLCL-PEG-PLCL) hydrogel had a wider gelation temperature range and better hydrolytic stability for about 4 weeks. Its controlled release curve is closest to the zero-order release kinetics.In vitro, PLCL-PEG-PLCL/Nell-1 could promote the chondrogenic expression and reduce the inflammatory expression.In vivo, TMJOA rabbits were mainly characterized by the disorder of cartilage structure and the destruction of subchondral bone. However, PLCL-PEG-PLCL/Nell-1 could reverse the destruction of the subchondral trabecula, restore the fibrous and proliferative layers of the surface, and reduce the irregular hyperplasia of fibrocartilage layer. In conclusion, by comparing the properties of different 3B-PEG IH, 20 wt% PLCL-PEG-PLCL hydrogel was selected as the most appropriate material. PLCL-PEG-PLCL/Nell-1 composite could reverse osteochondral damage caused by TMJOA, Nfatc1-Runx3 signaling pathway may play a role in it. This study may provide a novel, minimally-invasive therapeutic strategy for the clinical treatment of TMJOA.

2.
Arch Iran Med ; 24(9): 704-705, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34816688
3.
Polymers (Basel) ; 13(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502883

RESUMO

Polymer composites containing ferromagnetic fillers are promising for applications relating to electrical and electronic devices. In this research, the authors modified an ultraviolet light (UV) curable prepolymer to additionally cure upon heating and validated a permanent magnet-based particle alignment system toward fabricating anisotropic magnetic composites. The developed dual-cure acrylate-based resin, reinforced with ferromagnetic fillers, was first tested for its ability to polymerize through UV and heat. Then, the magnetic alignment setup was used to orient magnetic particles in the dual-cure acrylate-based resin and a heat curable epoxy resin system in a polymer casting approach. The alignment setup was subsequently integrated with a material jetting 3D printer, and the dual-cure resin was dispensed and cured in-situ using UV, followed by thermal post-curing. The resulting magnetic composites were tested for their filler loading, microstructural morphology, alignment of the easy axis of magnetization, and degree of monomer conversion. Magnetic characterization was conducted using a vibrating sample magnetometer along the in-plane and out-of-plane directions to study anisotropic properties. This research establishes a methodology to combine magnetic field induced particle alignment along with a dual-cure resin to create anisotropic magnetic composites through polymer casting and additive manufacturing.

4.
Front Mol Biosci ; 8: 675198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381812

RESUMO

Background: Epigenetic dysregulation via aberrant DNA methylation has gradually become recognized as an efficacious signature for predicting tumor prognosis and response to therapeutic targets. However, reliable DNA methylation biomarkers describing tumorigenesis remain to be comprehensively explored regarding their prognostic and therapeutic potential in breast cancer (BC). Methods: Whole-genome methylation datasets integrated from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were profiled (n = 1,268). A three-stage selection procedure (discovery, training, and external validation) was utilized to screen out the prominent biomarkers and establish a robust risk score from more than 300,000 CpG sites after quality control, rigorous filtering, and reducing dimension. Moreover, gene set enrichment analyses guided us to systematically correlate this epigenetic risk score with immunological characteristics, including immunomodulators, anti-cancer immunity cycle, immune checkpoints, tumor-infiltrating immune cells and a series of signatures upon modulating components within BC tumor microenvironment (TME). Multi-omics data analyses were performed to decipher specific genomic alterations in low- and high-risk patients. Additionally, we also analyzed the role of risk score in predicting response to several treatment options. Results: A 10-CpG-based prognostic signature which could significantly and independently categorize BC patients into distinct prognoses was established and sufficiently validated. And we hypothesize that this signature designs a non-inflamed TME in BC based on the evidence that the derived risk score is negatively correlated with tumor-associated infiltrating immune cells, anti-cancer immunity cycle, immune checkpoints, immune cytolytic activity, T cell inflamed score, immunophenoscore, and the vast majority of immunomodulators. The identified high-risk patients were characterized by upregulation of immune inhibited oncogenic pathways, higher TP53 mutation and copy number burden, but lower response to cancer immunotherapy and chemotherapy. Conclusion: Our work highlights the complementary roles of 10-CpG-based signature in estimating overall survival in BC patients, shedding new light on investigating failed events concerning immunotherapy at present.

5.
Oral Dis ; 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342085

RESUMO

OBJECTIVES: Many activities overload temporomandibular joint (TMJ) and cause mandibular condylar cartilage (MCC) degradation by inducing the expression of hypoxia-inducible factor-2α (HIF-2α). Although NF-κB signaling pathway has been reported to induce HIF-2α expression, the underlying mechanisms need to be verified. The aim was to investigate the effects of NF-κB/HIF-2α on MCC degradation induced by mechanical stress and the regulatory mechanism of NF-κB in the HIF-2α pathway. METHODS: Chondrocytes were subjected to cyclic compressive forces in a hypoxic environment. Western blotting was used to test the effects of stress on the expression of NF-κB and HIF-2α. HIF-2α siRNA and shRNA were constructed and transfected into MCC cells in vitro and in vivo to inhibit HIF-2α expression. To test the regulatory effect of the NF-κB pathway on HIF-2α, siRNA p65 was transfected into MCC. RESULTS: The results showed that mechanical stress could cause cartilage degradation and significantly increased the expression of NF-κB, HIF-2α, and downstream degradation factors (MMP13 and ADAMTs-4). Blockade of HIF-2α decreased cartilage degradation and related degradation factors. Suppression of p65 significantly decreased the expression of HIF-2α. CONCLUSIONS: Our results indicated that the upstream NF-κB pathway exerted a regulatory effect on HIF-2α in the degradation of MCC induced by stress.

6.
Oncogene ; 40(33): 5168-5181, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34218271

RESUMO

Fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) demethylase, participates in tumor progression and metastasis in many malignancies, but its role in colorectal cancer (CRC) is still unclear. Here, we found that FTO protein levels, but not RNA levels, were downregulated in CRC tissues. Reduced FTO protein expression was correlated with a high recurrence rate and poor prognosis in resectable CRC patients. Moreover, we demonstrated that hypoxia restrained FTO protein expression, mainly due to an increase in ubiquitin-mediated protein degradation. The serine/threonine kinase receptor associated protein (STRAP) might served as the E3 ligase and K216 was the major ubiquitination site responsible for hypoxia-induced FTO degradation. FTO inhibited CRC metastasis both in vitro and in vivo. Mechanistically, FTO exerted a tumor suppressive role by inhibiting metastasis-associated protein 1 (MTA1) expression in an m6A-dependent manner. Methylated MTA1 transcripts were recognized by an m6A "reader", insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which then stabilized its mRNA. Together, our findings highlight the critical role of FTO in CRC metastasis and reveal a novel epigenetic mechanism by which the hypoxic tumor microenvironment promotes CRC metastasis.

7.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(2): 212-221, 2021 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-34137227

RESUMO

Temporomandibular joint osteoarthritis (TMJOA) is mainly manifested as perforation of temporomandibular joint disc (TMJD) and destruction of condylar osteochondral complex (COCC). In recent years, tissue engineering technology has become one of the effective strategies in repairing this damage. With the development of scaffold material technology, composite scaffolds have become an important means to optimize the performance of scaffolds with the combined advantages of natural materials and synthetic materials. The gelling method with the minimally invasive concept can greatly solve the problems of surgical trauma and material anastomosis, which is beneficial to the clinical transformation of temporomandibular joint tissue engineering. Extracellular matrix scaffolds technology can solve the problem of scaffold source and maximize the simulation of the extracellular environment, which provides an important means for the transformation of temporo joint tissue engineering to animal level. Due to the limitation of the source and amplification of costal chondrocytes, the use of mesenchymal stem cells from different sources has been widely used for temporomandibular joint tissue engineering. The fibrochondral stem cells isolated from surface layer of articular cartilage may provide one more suitable cell source. Transforming growth factor ß superfamily, due to its osteochondrogenesis activity has been widely used in tissue engineering, and platelet-rich derivative as a convenient preparation of compound biological factor, gradually get used in temporomandibular joint tissue engineering. With the deepening of research on extracellular microenvironment and mechanical stimulation, mesenchymal stem cells, exosomes and stress stimulation are increasingly being used to regulate the extracellular microenvironment. In the future, the combination of complex bioactive factors and certain stress stimulation may become a trend in the temporomandibular joint tissue engineering research. In this article, the progress on tissue engineering in repairing COCC and TMJD, especially in scaffold materials, seed cells and bioactive factors, are reviewed, so as to provide information for future research design and clinical intervention.


Assuntos
Células-Tronco Mesenquimais , Engenharia Tecidual , Animais , Articulação Temporomandibular/cirurgia , Disco da Articulação Temporomandibular/cirurgia , Tecidos Suporte
8.
Front Mol Biosci ; 8: 639079, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095219

RESUMO

Patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) were treated with immediate or sequential withdrawal after 5 days of systemic glucocorticoids. The effects of the two withdrawal methods on the prognosis of patients were compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, double-blind, parallel-controlled, open-label study was conducted in the respiratory department of tertiary hospitals in Central China. Patients met inclusion criteria for AECOPD and needed to use systemic glucocorticoids. They were randomly assigned to immediate and sequential withdrawal groups at a 1:1 ratio. The study was completed in August 2020 and is registered at the China Clinical Trials Registry (Chictr.org) (ChiCTR1800018894). According to general data and clinical characteristics, there were no statistically significant differences between the 329 patients in the immediate withdrawal group and the 310 patients in the sequential withdrawal group (P > 0.05). At the 30, 90, 180, and 360-days follow-up, the acute exacerbation frequency, rehospitalization rate, mortality, and intensive care unit (ICU) treatment rate were not significantly different between the immediate withdrawal group and sequential withdrawal group (P > 0.05). The modified Medical Research Council (mMRC) and COPD assessment test (CAT) scores were also not significantly different between the two groups. At the 180- and 360-day follow-up, forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups (P > 0.05). The time from discharge to first acute exacerbation was significantly lower in the immediate withdrawal group (46.12 days) than in sequential withdrawal group (49.02 days) (P < 0.05). The time of stay in the hospital for the first time after discharge was not significantly different between the two groups (P > 0.05). Adverse events were not significantly different between the immediate withdrawal group and sequential withdrawal group (P < 0.05). Subgroup analysis was performed according to age, degree of disease, and relevant indicators. At the 30-day follow-up, the acute exacerbation frequency of patients with advanced age, high global strategy for chronic obstructive lung disease (GOLD), and high fractional exhaled nitric oxide was significantly higher in the immediate withdrawal group than in the sequential withdrawal group (P < 0.05). In addition, according to receiver operating characteristic (ROC) curve analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly higher in patients with age > 63.5 years or GOLD > 3 in the immediate withdrawal group than in the sequential withdrawal group, suggesting that the short-term efficacy was poor.

9.
J Clin Lab Anal ; 35(6): e23782, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33942374

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD-ILD) has not been determined. METHODS: A two-stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD-ILD cases, and 225 controls). RESULTS: We identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212-4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376-4.128, p = 0.002 in stage two). However, we did not observe this association in CTD-ILD (OR = 1.401, 95% CI = 0.790-2.485, p = 0.248). CONCLUSION: Our findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD-ILD.

10.
J Clin Lab Anal ; 35(6): e23813, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33969541

RESUMO

BACKGROUND: Although studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals. METHODS: To identify genetic risk factors for asthma in a Han Chinese population, 211 asthma-related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next-generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls). RESULTS: First, we identified 18 potentially functional rare loss-of-function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant (p < 0.05) burdens of rare nonsynonymous variants in 10 genes. Third, 23 common single-nucleotide polymorphisms were associated with the risk of asthma, 7/23 (30.4%) and 9/23 (39.1%) of which were modestly significant (p < 9.1 × 10-4 ) in the Replication Cohort and Combined Cohort, respectively. According to our cumulative risk model involving the modestly associated alleles, middle- and high-risk subjects had a 2.0-fold (95% CI: 1.621-2.423, p = 2.624 × 10-11 ) and 6.0-fold (95% CI: 3.623-10.156, p = 7.086 × 10-12 ) increased risk of asthma, respectively, compared with low-risk subjects. CONCLUSION: This study revealed novel rare and common genetic risk factors for asthma, and provided a cumulative risk model for asthma risk prediction and stratification in Han Chinese individuals.

11.
ACS Appl Mater Interfaces ; 13(17): 20014-20023, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33853324

RESUMO

The solid-state method is extensively applied to the synthesis of electrode materials for its simplicity and low cost. However, particles obtained using the traditional solid-state method exhibited a large, uneven particle size and a severe aggregation phenomenon, leading to an unsatisfactory electrochemical performance. Here, spinel LiNi0.5Mn1.5O4 (LNMO) with good dispersion was synthesized using the solid-state method with the addition of N,N-dimethylpyrrolidone (NMP). During the LNMO preparation process, NMP is effective in refining and optimizing the particle size and suppressing the aggregation phenomenon. Meanwhile, the N element migration phenomenon was also observed in the bulk of LNMO, and it was beneficial for extending solid-solute reactions as demonstrated by in situ X-ray diffraction. LNMO prepared with NMP (LNMO-N-x) exhibited a higher discharge voltage and capacity (115.3 mA h g-1 at 2 C) compared with LNMO (105.8 mA h g-1). These results reveal the function of NMP in the preparation of LNMO and the effect of the physical characteristic changes on structure and phase transition in a working battery, and it can be easily incorporated into other electrode materials; if well engineered, it will contribute a lot to the further applications of lithium ion batteries.

12.
Front Cell Dev Biol ; 9: 656153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33869221

RESUMO

Background: Temporomandibular joint osteoarthritis (TMJOA) seriously affects the health of patients, and the current treatments are invasive and only used for advanced cases. Bone marrow mesenchymal stem cell (BMSC)-derived small extracellular vesicles (BMSC-sEVs) may represent a safer and more effective treatment, but their role in TMJOA has not been elucidated. This study attempted to analyze the cartilage reconstruction effect of BMSC-sEVs on TMJOA and the mechanism underlying this effect. Methods: BMSC-sEVs were isolated and purified by microfiltration and ultrafiltration and were subsequently characterized by nanoparticle tracking analysis, electron microscopy, and immunoblotting. TMJOA models were established in vivo and in vitro, and hematoxylin-eosin staining, immunohistochemistry, and histological scoring were performed to analyze the histological changes in TMJOA cartilage tissues treated with BMSC-sEVs. The proliferation, migratory capacity, and cell cycle distribution of TMJOA cartilage cells treated with BMSC-sEVs were detected. Furthermore, the related mechanisms were studied by bioinformatic analysis, immunoblotting, and quantitative PCR, and they were further analyzed by knockdown and inhibitor techniques. Results: The acquisition and identification of BMSC-sEVs were efficient and satisfactory. Compared with the osteoarthritis (OA) group, the condylar tissue of the OA group treated with BMSC-sEV (OAsEV) showed an increase in cartilage lacuna and hypertrophic cartilage cells in the deep area of the bone under the cartilage. Significantly upregulated expression of proliferating cell nuclear antigen and cartilage-forming factors and downregulated expression of cartilage inflammation-related factors in OAsEV were observed. In addition, we found higher rates of cell proliferation and migratory activity and alleviated G1 stagnation of the cell cycle of OAsEV. Autotaxin was found in the BMSC-sEVs, and key factors of the Hippo pathway, Yes-associated protein (YAP), phosphorylated Yes-associated protein (p-YAP), etc. were upregulated in the OAsEV group. Treatment with BMSC-sEVs after autotaxin knockdown or inhibition no longer resulted in expression changes in cartilage-forming and inflammation-related factors and key factors of the Hippo pathway. Conclusions: These results suggest that the autotaxin-YAP signaling axis plays an important role in the mechanism by which BMSC-sEVs promote cartilage reconstruction in TMJOA, which may provide guidance regarding their therapeutic applications as early and minimally invasive therapies for TMJOA, and provide insight into the internal mechanisms of TMJOA.

13.
Plant Physiol Biochem ; 163: 108-118, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33826995

RESUMO

Early seedling development is one of the most crucial period of the plant's life cycle, which is highly susceptible to adverse environmental conditions, especially those impose by salt stress. Castor plant (Ricinus communis) is a famous non-edible oilseed and salt-resistant crop worldwide. However, the specific metabolic responses in the cotyledons and roots of this species during seedling establishment under salt stress are still not clearly understood. In the present study, 16 d castor seedlings were treated with 150 mM NaCl for 6 d, and the metabolite profiling of cotyledons and roots was conducted using liquid chromatography (LC) combined with electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS). The Principal Component Analysis (PCA) results showed that the metabolites were great differed in cotyledons and roots under salt stress. There were 38 differential metabolites, mainly including fatty acid, nucleic acid and organic acids in the cotyledons, but only 19 differential metabolites, mainly including fatty acid and organic acids in the roots under such condition. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that flavone and flavonol biosynthesis, pantothenate and CoA biosynthesis, citrate cycle and carotenoid biosynthesis were the common metabolic pathways in response to salt stress in the two organs. Salt stress caused metabolite process alteration mainly on carbon and nitrogen metabolisms, and the carbon allocation from root to cotyledon was increased. Additionally, changes of amino acids and nucleic acids profiles were only found in the cotyledons, and the roots could enhance the activity of antioxidant enzyme systems to scavenge ROS under salinity. In conclusion, the present research provides an improved understanding on specific physiological changes in the cotyledons in castor early seedlings, and explores their interaction under salt stress.


Assuntos
Cotilédone , Plântula , Cromatografia Líquida , Metabolômica , Raízes de Plantas , Ricinus , Estresse Salino , Espectrometria de Massas em Tandem
14.
Cancer Med ; 10(7): 2423-2441, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33666372

RESUMO

BACKGROUND: Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR-125b-2-3p, has been identified for predicting chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR-125b-2-3p in advanced CRC under chemotherapy have yet to be elucidated. METHODS: MiR-125b-2-3p expression was detected by real-time PCR (RT-PCR) in CRC tissues. The effects of miR-125b-2-3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR-125b-2-3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on. RESULTS: MiR-125b-2-3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR-125b-2-3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR-125b-2-3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR-125b-2-3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR-125b-2-3p inhibited the proliferation and epithelial-mesenchymal transition (EMT) of CRC induced by lncRNA XIST. CONCLUSIONS: Lower miR-125b-2-3p expression resulted in lower sensitivity of CRC to chemotherapy and was correlated with poorer survival of CRC patients. LncRNA XIST promoted CRC metastasis acting as a ceRNA for miR-125b-2-3p to mediate WEE1 expression. LncRNA XIST-miR-125b-2-3p-WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , MicroRNAs/metabolismo , Proteínas Tirosina Quinases/metabolismo , RNA Longo não Codificante/metabolismo , Idoso , Animais , Antineoplásicos/uso terapêutico , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Células HCT116 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Proteínas Tirosina Quinases/genética , Reação em Cadeia da Polimerase em Tempo Real , Ensaio Tumoral de Célula-Tronco , Regulação para Cima
15.
ACS Omega ; 6(11): 7655-7668, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33778276

RESUMO

An effective NO x prediction model is the basis for reducing pollutant emissions. In this paper, a real-time NO x prediction model based on an ensemble deep belief network (DBN) is proposed. Variable importance projection analysis is adopted to screen variables, the time delay of each variable is estimated, and the phase space of the original sample is reconstructed by analyzing the historical data. An ensemble strategy based on random subspace is presented, including the data set partition method and ensemble mode of the model. First, subspaces are constructed according to the component information extracted by partial least squares. Then, the deep belief network is used as a submodel. Finally, a back propagation neural network is developed for model combination. The ensemble deep belief network model has been used to model the NO x emission prediction of a 660 MW boiler. The simulation results show that the ensemble DBN model can fully exploit the nonlinear mapping relationship between input variables and NO x concentration by using various learning learners. Compared with the back propagation neural network and support vector machine, which are commonly used in NO x modeling, the ensemble DBN model has better prediction performance and generalization ability.

16.
J Hazard Mater ; 402: 123459, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32683157

RESUMO

Perfluorooctanoic acid (PFOA) is highly stable due to the strong CF bond and extremely difficult to be removed by conventional photocatalysts. In this study, Bi doped BiOI1-xFx solid solutions with hollow microsphere structure were prepared through a facile one-step hydrothermal method. Compared with pure BiOI and BiOF, the band gap of the Bi/BiOI1-xFx solid solutions was significantly reduced, thus promoting the visible light absorbance. The cavity structure of the BiOI1-xFx solid solutions enhanced the surface areas and active sites for reaction. The local electromagnetic field dominated by surface plasmon resonance (SPR) effect of Bi metal on the surface favored the separation of the photoinduced charge pairs. As a consequence, Bi/BiOI0.8F0.2 (x = 0.20, the doping amount of fluorine was 20 %) composite displayed the best photocatalytic performance for decomposing PFOA, and 40 mg/L PFOA could be removed within 2 h illumination. The degradation rate constant (k = 0.0375 min-1) of PFOA by Bi/BiOI0.8F0.2 was about tenfold of that by pure BiOI and BiOF. Superoxide radical (·O2-) predominated in the degradation of PFOA by Bi/BiOI0.8F0.2, and the possible degradation pathway of PFOA by Bi/BiOI0.8F0.2 was proposed. This work provides a highly efficient catalyst for the practical application in removal of highly persistent PFOA.

17.
Int J Mol Med ; 46(6): 2115-2125, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33125101

RESUMO

Oral cancer (OC) is the most common type of head and neck malignant tumor. Tumor­derived exosomes induce a complex extracellular environment that affects tumor immunity. In the present study, exosomes were isolated from OC cell lines (WSU­HN4 and SCC­9) by ultrafiltration and the protein content of these oral cancer­derived exosomes (OCEXs) was analyzed by mass spectrometry, which revealed the enrichment of transforming growth factor (TGF)­ß1. Natural killer (NK) cells were examined by flow cytometry following co­culture with OCEXs. The expression of killer cell lectin like receptor K1 (KLRK1; also known as NKG2D, as used herein) and natural cytotoxicity triggering receptor 3 (NCR3; also known as NKp30, as used herein) in NK cells was found to be significantly upregulated following co­culture with the OCEXs for 1 day, whereas this expression decreased at 7 days. Killer cell lectin like receptor C1 (KLRC1; also known as NKG2A; as used herein) expression exhibited an opposite trend at 1 day. In addition, NK cell cytotoxicity against the OC cells was enhanced at 1 day, but was attenuated at 7 days. TGF­ß1 inhibited the function of NK cells at 7 days, whereas it had no obvious effects at 1 and 3 days. On the whole, the findings of the present study reveal changes in NK cell function and provide new insight into NK cell dysfunction.


Assuntos
Exossomos/metabolismo , Células Matadoras Naturais/metabolismo , Neoplasias Bucais/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Receptor 3 Desencadeador da Citotoxicidade Natural/metabolismo , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Humanos , Proteômica , Fator de Crescimento Transformador beta1
18.
Clin Transl Immunology ; 9(10): e1173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33033616

RESUMO

Objectives: Although the genomic landscape of small-cell carcinoma of the oesophagus (SCCE) has been dissected, its transcriptome-level aberration and immune microenvironment status are unknown. Methods: Using ultra-deep whole transcriptome sequencing, we analysed the expression profile of nine paired SCCE samples and compared the transcriptome with public transcriptomic data set of normal oesophageal mucosa and other cancer types. Based on the transcriptome data, the immune signatures were investigated. The genomic data of 55 SCCE samples were also applied for immune checkpoint blockade therapy (ICBT) biomarker evaluation including microsatellite instability (MSI) status, tumor mutation burden (TMB) and neoantigen burden (TNB). Also, we evaluated the CD8, CD68 and programmed death-ligand 1 (PD-L1) in 62 retrospective SCCE samples with IHC assay. Results: Differential expression analysis revealed that the cell cycle, p53, and Wnt pathways are significantly deregulated in SCCE. Immune microenvironment analysis showed that high leucocyte infiltration and adaptive immune resistance did occur in certain individuals, while the majority showed a relatively suppressive immune status. Immune checkpoints such as CD276 and LAG-3 were upregulated, and higher M2 macrophage infiltration in tumor tissues. Furthermore, normal tissues adjacent to the tumors of SCCE presented a more activated inflammatory status than tumor-free healthy controls. These observations showed that ICBT might benefit SCCE patients. As the critical biomarker of ICBT, TMB of SCCE was 3.64 with the predictive objective response rate 13.2%, while the PD-L1-positive rate was 43%. Conclusions: Our study systematically characterized the immune microenvironment in small-cell carcinoma of the esophagus and provided evidence that several patients with SCCE may benefit from immune checkpoint blockade therapy.

19.
Cancer Commun (Lond) ; 40(11): 620-632, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32914570

RESUMO

BACKGROUND: Inherited susceptibility accounts for nearly one-third of colorectal cancer (CRC) predispositions and has an 80%-100% lifetime risk of this disease. However, there are few data about germline mutations of hereditary CRC-related genes in Chinese patients with CRC. This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC, differences between Chinese and Western patients, and the phenotype-genotype correlation. METHODS: We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing. A series of bioinformatic analyses, as well as statistical comparisons, were performed. RESULTS: We found that 77 patients (14.6%) harbored functional variants of the 12 genes. The mutation frequencies of the top 5 mutated genes were 6.5% for MutL homolog 1 (MLH1), 5.1% for MutS homolog 2 (MSH2), 1.0% for MSH6, 0.8% for PMS1 homolog 2 (PMS2), and 0.8% for APC regulator of the WNT signaling pathway (APC). Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair (MMR) genes as compared with those in Western populations. Mutations in MLH1, MSH2, and MSH6 were found to be mutually exclusive. Patients with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer (MLH1: 20.6% vs. 8.7%; MSH2: 25.9% vs. 8.6%) and family history of cancer than those without these mutations (MLH1: 73.5% vs. 48.4%; MSH2: 70.4% vs. 48.9%), and the lesions were more prone to occur on the right side of the colon than on the left side (MLH1: 73.5% vs. 29.3%; MSH2: 56.0% vs. 31.0%). The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations (70.6% vs. 50.7%), and the rate of polyps was higher in patients with APC mutations than in those with wild-type APC (75.0% vs. 17.4%). CONCLUSION: These results provide a full-scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi-gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.


Assuntos
Neoplasias Colorretais , Mutação em Linhagem Germinativa , Idoso , China , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Feminino , Células Germinativas , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Estudos Retrospectivos
20.
Mol Ecol ; 29(9): 1642-1656, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32285491

RESUMO

The degree to which adaptation to similar selection pressures is underlain by parallel versus non-parallel genetic changes is a topic of broad interest in contemporary evolutionary biology. Sticklebacks provide opportunities to characterize and compare the genetic underpinnings of repeated marine-freshwater divergences at both intra- and interspecific levels. While the degree of genetic parallelism in repeated marine-freshwater divergences has been frequently studied in the three-spined stickleback (Gasterosteus aculeatus), much less is known about this in other stickleback species. Using a population transcriptomic approach, we identified both genetic and gene expression variations associated with marine-freshwater divergence in the nine-spined stickleback (Pungitius pungitius). Specifically, we used a genome-wide association study approach, and found that ~1% of the total 173,491 identified SNPs showed marine-freshwater ecotypic differentiation. A total of 861 genes were identified to have SNPs associated with marine-freshwater divergence, but only 12 of these genes have also been reported as candidates associated with marine-freshwater divergence in the three-spined stickleback. Hence, our results indicate a low degree of interspecific genetic parallelism in marine-freshwater divergence. Moreover, 1,578 genes in the brain and 1,050 genes in the liver were differentially expressed between marine and freshwater nine-spined sticklebacks, ~5% of which have also been identified as candidates associated with marine-freshwater divergence in the three-spined stickleback. However, only few of these (e.g., CLDND1) appear to have been involved in repeated marine-freshwater divergence in nine-spined sticklebacks. Taken together, the results indicate a low degree of genetic parallelism in repeated marine-freshwater divergence both at intra- and interspecific levels.


Assuntos
Evolução Biológica , Smegmamorpha , Transcriptoma , Animais , Água Doce , Estudos de Associação Genética , Oceanos e Mares , Smegmamorpha/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...