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1.
Mol Med Rep ; 24(6)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34643245

RESUMO

The aim of the present study was to investigate the effect of hedgehog­interacting protein antisense RNA 1 (HHIP­AS1) on epithelial­mesenchymal transition (EMT) and cellular stemness of human lung cancer cells by regulating the microRNA (miR)­153­3p/PCDHGA9 axis. Reverse transcription­quantitative PCR was used to compare the expression of HHIP­AS1 in lung cancer and adjacent normal lung tissues. In addition, the correlation of HHIP­AS1 with E­cadherin, Vimentin, N­cadherin and Twist1 was analyzed. HHIP­AS1 overexpression vector was transfected into lung cancer A549 and NCI­H1299 cell lines. Cell Counting Kit­8 and Transwell and clonogenic assays were used to detect the proliferation, invasion and clonogenesis of the lung cancer cells, respectively. The associations among HHIP­AS1, miR­153­3p and PCDHGA9 were predicted by bioinformatics analysis and verified by a dual­luciferase reporter system. The results showed that the expression of HHIP­AS1 in lung cancer tissues was significantly lower than that in normal tissues (P<0.001). HHIP­AS1 was positively correlated with E­cadherin and negatively correlated with Vimentin, N­cadherin and Twist1. HHIP­AS1 overexpression inhibited the proliferation, invasion and clonal formation of the A549 and NCI­H1299 cells. The luciferase reporter system verified that HHIP­AS1 could adsorb miR­153­3p and that PCDHGA9 was the target gene of miR­153­3p. A549 cells were transfected with HHIP­AS1 overexpression vector and miR­153­3p mimic, and the miR­153­3p mimic had a mitigating effect on HHIP­AS1 inhibition (P<0.001). In conclusion, HHIP­AS1 inhibits the EMT and stemness of lung cancer cells by regulating the miR­153­3p/PCDHGA9 axis. Thus, HHIP­AS1 may be a new potential target for lung cancer treatment.

2.
Int J Biol Macromol ; 188: 983-992, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34403677

RESUMO

Plant laccases have been proposed to participate in lignin biosynthesis. However, there is no direct evidence that individual laccases in Populus can polymerize lignin monomers and alter cell wall structure. Here, a Populus laccase, PtrLAC16, was expressed and purified in a eukaryotic system. Enzymatic analysis of PtrLAC16 showed that it could polymerize lignin monomers in vitro. PtrLAC16 preferred sinapyl alcohol, and this preference is associated with an altered S/G ratio in transgenic Populus lines. PtrLAC16 was localized exclusively in the cell walls of stem vascular tissue, and a reduction in PtrLAC16 expression led to a significant decrease in lignin content and altered cell wall structure. There was a direct correlation between the inhibition of PtrLAC16 expression and structural changes in the stem cell wall of Populus. This study provides direct evidence that PtrLAC16 plays a key role in the polymerization of lignin monomers, especially for sinapyl lignin, and affects the formation of xylem cell walls in Populus.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34424850

RESUMO

The feature pyramid has been widely used in many visual tasks, such as fine-grained image classification, instance segmentation, and object detection, and had been achieving promising performance. Although many algorithms exploit different-level features to construct the feature pyramid, they usually treat them equally and do not make an in-depth investigation on the inherent complementary advantages of different-level features. In this article, to learn a pyramid feature with the robust representational ability for action recognition, we propose a novel collaborative and multilevel feature selection network (FSNet) that applies feature selection and aggregation on multilevel features according to action context. Unlike previous works that learn the pattern of frame appearance by enhancing spatial encoding, the proposed network consists of the position selection module and channel selection module that can adaptively aggregate multilevel features into a new informative feature from both position and channel dimensions. The position selection module integrates the vectors at the same spatial location across multilevel features with positionwise attention. Similarly, the channel selection module selectively aggregates the channel maps at the same channel location across multilevel features with channelwise attention. Positionwise features with different receptive fields and channelwise features with different pattern-specific responses are emphasized respectively depending on their correlations to actions, which are fused as a new informative feature for action recognition. The proposed FSNet can be inserted into different backbone networks flexibly, and extensive experiments are conducted on three benchmark action datasets, Kinetics, UCF101, and HMDB51. Experimental results show that FSNet is practical and can be collaboratively trained to boost the representational ability of existing networks. FSNet achieves superior performance against most top-tier models on Kinetics and all models on UCF101 and HMDB51.

5.
Sensors (Basel) ; 21(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34450942

RESUMO

In the important and challenging field of environmental sound classification (ESC), a crucial and even decisive factor is the feature representation ability, which can directly affect the accuracy of classification. Therefore, the classification performance often depends to a large extent on whether the effective representative features can be extracted from the environmental sound. In this paper, we firstly propose a sub-spectrogram segmentation with score level fusion based ESC classification framework, and we adopt the proposed convolutional recurrent neural network (CRNN) for improving the classification accuracy. By evaluating numerous truncation schemes, we numerically figure out the optimal number of sub-spectrograms and the corresponding band ranges, and, on this basis, we propose a joint attention mechanism with temporal and frequency attention mechanisms and use the global attention mechanism when generating the attention map. Finally, the numerical results show that the two frameworks we proposed can achieve 82.1% and 86.4% classification accuracy on the public environmental sound dataset ESC-50, respectively, which is equivalent to more than 13.5% improvement over the traditional baseline scheme.


Assuntos
Redes Neurais de Computação , Som
6.
Molecules ; 26(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199966

RESUMO

Nanfeng mandarins (Citrus reticulata Blanco cv. Kinokuni), Xunwu mandarins (Citrus reticulata Blanco), Yangshuo kumquats (Citrus japonica Thunb) and physiologically dropped navel oranges (Citrus sinensis Osbeck cv. Newhall) were used as materials to extract peel essential oils (EOs) via hydrodistillation. The chemical composition, and antibacterial and antioxidant activities of the EOs were investigated. GC-MS analysis showed that monoterpene hydrocarbons were the major components and limonene was the predominate compound for all citrus EOs. The antibacterial testing of EOs against five different bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium) was carried out using the filter paper method and the broth microdilution method. Kumquat EO had the best inhibitory effect on B. subtilis, E. coli and S. typhimurium with MIC (minimum inhibitory concentration) values of 1.56, 1.56 and 6.25 µL/mL, respectively. All citrus EOs showed the antioxidant activity of scavenging DPPH and ABTS free radicals in a dose-dependent manner. Nanfeng mandarin EO presented the best antioxidant activity, with IC50 values of 15.20 mg/mL for the DPPH assay and 0.80 mg/mL for the ABTS assay. The results also showed that the antibacterial activities of EOs might not be related to their antioxidant activities.


Assuntos
Antibacterianos/química , Antioxidantes/química , Citrus/química , Óleos Voláteis/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Bacillus subtilis/efeitos dos fármacos , Citrus/classificação , Destilação , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Vegetais/química , Óleos Vegetais/isolamento & purificação , Óleos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
7.
Biomed Pharmacother ; 142: 111652, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34112534

RESUMO

Chemotherapy resistance remains to be the primary barrier to acute myeloid leukemia (AML) treatment failure. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been well established as a truly pleiotropic transcription factor. Inhibition of Nrf2 function increases the sensitivity of various chemotherapeutics and overcomes chemoresistance effectively. Brusatol (Bru) has been reported to decrease Nrf2 protein expression specifically by ubiquitin degradation of Nrf2. However, it remains elusive whether combination of Brusatol and Cytarabine (Ara-C) elicits a synergistic antitumor effect in AML. Our results demonstrated that combination of Ara-C and Brusatol synergistically exerted remarkable pro-apoptosis effect in HL-60 and THP-1 cells. Mechanistically, synergistic anti-tumor effect of Ara-C/Brusatol in AML cells is mediated by attenuating Nrf2 expression. To our surprise, Nrf2 inhibition by Brusatol causes downregulation of the expression of glycolysis-related proteins and decreased glucose consumption and lactate production, whereas the level of ROS production was unaffected. The activation of Nrf2 by Sulforaphane (SFP) could reverse the chemotherapeutic effect and changes of glycolysis of concomitant of Ara-C with Brusatol in AML cell lines. Additionally, Ara-C/Brusatol co-treatment decreased Glucose-6-phosphate dehydrogenase (G6PD) protein expression and increased the sensitivity of Ara-C. Moreover, the mouse xenograft in vivo experiment confirmed that combining Ara-C with Brusatol exerted stronger antileukemia than Ara-C alone. The efficacy, together with the mechanistic observations, reveals the potential of simultaneously giving these two drugs and provides a rational basis for targeting glucose catabolism in future clinical therapeutic approach.

8.
J Mater Sci Mater Med ; 32(6): 72, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34125310

RESUMO

To find out the optimal porosity and pore size of porous titanium (Ti) regarding the cytocompatibility and osteogenic differentiation. Six groups of porous Ti samples with different porosities and pore sizes were fabricated by the powder metallurgy process. The microstructure and compressive mechanical properties were characterized. The cytocompatibility was examined by a series of biological tests as protein absorption with BCA assay kit, cell attachment with laser scanning confocal microscopy and vinculin expression, cell proliferation with CCK-8 assay. Cell differentiation and calcification were detected by qPCR and Alizarin Red S dying respectively. Pores distributed homogeneously throughout the porous Ti samples. The compressive test results showed that Young's modulus ranged from 2.80 ± 0.03 GPa to 5.43 ± 0.34 GPa and the compressive strength increased from 112.4 ± 3.6 MPa to 231.1 ± 9.4 MPa. Porous Ti with high porosity (53.3 ± 1.2%) and small pore size (191.6 ± 3.7 µm) adsorbed more proteins. More MC3T3-E1 cells adhered onto dense Ti samples than onto any other porous ones already after culture and no difference was identified within the porous groups. The porous structure of porous Ti with a porosity of 53.3 ± 1.2% and an average pore size of 191.6 ± 3.7 µm facilitated cell differentiation and calcification. Small pores were not beneficial to the osteo-initiation at the very beginning. Porous Ti with a porosity of 53.3 ± 1.2% and an average pore size of 191.6 ± 3.7 µm fabricated by powder metallurgy process showed the expected mechanical property and improved osseointegration as implants in dental treatment.

9.
Pharmacol Res Perspect ; 9(3): e00774, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33939886

RESUMO

This meta-analysis was performed to compare the safety, efficacy, and pharmacoeconomic of bivalirudin versus heparin in high-risk patients for percutaneous coronary interventions (PCI). Earlier meta-analysis comparing bivalirudin and heparin during PCI demonstrated that bivalirudin caused less bleeding with more stent thrombosis. However, little data were available on the safety of bivalirudin versus heparin in high-risk patients for PCI. Thus, we performed a meta-analysis to evaluate the efficacy and safety in the "high-risk" patients. A systematic search of electronic databases was conducted up to July 30, 2020. The Cochrane Risk of Bias assessment tool was used to assess the quality of included studies. The primary outcomes were all-cause death and major adverse cardiac events (MACE); secondary outcomes were major and minor bleeding, followed by a cost-minimization analysis comparing bivalirudin and heparin using a local drug and medical costs reported in China. Subgroup analysis was based on the type of disease of the high-risk population. Finally, a total of 10 randomized controlled trials involved 42,699 patients were collected. The Cochrane Risk of Bias Tool was employed to appraise the research quality. No significant difference was noted between bivalirudin and heparin regarding all-cause death and MACE. However, subgroup analysis showed that bivalirudin caused less major bleeding in female (OR:0.65, 95% CI:0.53-0.79), diabetes (OR:0.55, 95%CI:0.42-0.73), and CKD (OR:0.59, 95%CI:0.63-1.65). The scatterers of the included literature were approximately symmetrical, and no research was outside the funnel plot. Additionally, cost-minimization analysis showed that heparin was likely to represent a cost-effective option compared with bivalirudin in China, with potential savings of 2129.53 Chinese Yuan (CNY) per patient for one PCI. Overall, the meta-analysis showed that although bivalirudin appeared to have a lower risk of major bleeding rate, the overall effectiveness and safety between the two groups showed no significant difference in high-risk patients for PCI. But the results of the cost-minimization analysis showed that heparin could be a potential cost-saving drug than bivalirudin in patients for PCI in China.

10.
Front Immunol ; 12: 632864, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968024

RESUMO

Chronic periaortitis (CP) is a rare autoimmune disease without effective treatment. By analyzing the serum bile acid spectrum in 28 CP patients with the ultra-performance liquid chromatography-tandem mass spectrometry, we found that the bile acids were significantly altered in CP patients, with significant increases in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) and decrease in deoxycholic acid (DCA). Signaling pathway enrichment analysis from the RNA sequencing results suggested that the altered gene sets in PBMC of CP patients were associated with bile acid metabolism. Furthermore, we found that pathological concentration of CDCA could significantly inhibited IL-6 expression in RAW 264.7 cells after LPS stimulation. Since CDCA is a well-known natural high-affinity ligand for the bile acid receptor farnesoid-x-receptor (FXR) while GW4064 is the synthetic specific agonist of this receptor, we then revealed that GW4064 significantly decreased IL-6 expression in RAW 264.7 cells and bone marrow-derived macrophages but not in FXR-/- macrophages upon LPS stimulation. The western blot results with the anti-FXR antibody showed significantly increased expression in the nuclear proportion, suggesting that FXR agonist promoted the transportation of FXR into the nucleus but did not increase the FXR expression in macrophages. Dual-luciferase report assay and ChIP assay demonstrated that upon activation, FXR could directly bind to the promoter site of IL-6, leading to the decreased expression of IL-6. Thus, bile acids, especially CDCA, may operate to damp inflammation via FXR-mediated downregulation of IL-6 in mononuclear cells and provide a protective mechanism for CP patients.


Assuntos
Ácidos e Sais Biliares/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Fibrose Retroperitoneal/metabolismo , Idoso , Animais , Ácidos e Sais Biliares/sangue , Núcleo Celular/metabolismo , Ácido Quenodesoxicólico/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Interleucina-6/genética , Isoxazóis/farmacologia , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Células RAW 264.7 , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/genética , Fibrose Retroperitoneal/sangue , Transdução de Sinais
11.
Huan Jing Ke Xue ; 42(6): 2668-2678, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34032066

RESUMO

As an important component of atmospheric aerosols, black carbon (BC) has a great influence on the regional and global radiation balance, climate, and human health due to its small particle size, large specific surface area, and radiative forcing potential. Here, the spatio-temporal characteristics of atmospheric BC were investigated based on modern-era retrospective analysis for research and applications version 2 (MERRA-2) reanalysis data and ground observation data during 1980-2019 in Shanghai, a highly urbanized city in mainland China. The influences of local emissions and regional transmission on regional-scale BC concentrations were examined using the M-K trend test, backward trajectory analysis, and the potential source contribution function (PSCF). The results showed that:① MERRA-2 BC and ground observation datasets showed good consistency (R∈[0.68, 0.72]), indicating that MERRA-2 reanalysis data can be used to reveal long-term changes in ground-level atmospheric BC concentrations; ② Atmospheric BC concentrations in Shanghai over the past 40 years can be divided into three stages:a "low value" stage of slow growth[1980-1986, (1.75±0.17) µg·m-3], a relatively stable "median value" stage[1987-1999, (2.18 ±0.07) µg·m-3], and a fluctuating "high value" stage[2000-2019, (3.07±0.31) µg·m-3]. Seasonally, Shanghai's BC concentrations generally show a "U" pattern with low concentrations in summer and high concentrations in winter. As a result of black carbon emissions from marine diesel engines and other engines used for water transportation, a small peak also occurs in July; ③ The diagnostic quality ratio of air pollutants and the bivariate correlation analysis[R(BC-NO2)>R(BC-CO)>R(BC-SO2)] indicated that traffic emissions were the main sources of atmospheric BC in Shanghai, especially by heavy diesel vehicles; ④ The backward trajectory and PSCF analyses found that the air mass of Shanghai in summer was dominated by a clean sea breeze, accounting for 77.18%. In contrast, during the other seasons, more than 50% of the air mass came from the north. The potential source regions of atmospheric BC in Shanghai are mainly distributed in eastern China, expanding outwards and centering on the Yangtze River Delta, and the expansion direction is consistent with the directions of the backward trajectories.

12.
Materials (Basel) ; 14(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808233

RESUMO

A large amount of cow hair solid waste is produced in leather production, and a reasonable treatment should be developed to reduce the pollution. In this study, cow hair waste was utilized as the carbon precursor, and N2 was determined to be the most appropriate atmosphere for biochar preparation. We performed a comparison of the properties of biochars that were prepared with different methods, including direct pyrolysis, KOH activation, and the MgO template method. The characterization results show that the highest specific surface area reaches 1753.075 m2/g. Subsequently, the keratin that was extracted from cow hair and purified was used to prepare a biochar with the MgO template method, obtaining an orderly sponge structure. The biochar from cow hair waste was further used to absorb direct blue dye wastewater, and its adsorption capacity reached 1477 mg/g after 10 h with a high efficiency of regeneration. This study successfully utilized keratin-containing hair waste and provides a new source for synthesizing carbon materials for dye wastewater treatment.

13.
Ying Yong Sheng Tai Xue Bao ; 32(4): 1406-1416, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33899409

RESUMO

Based on the ground-based observations from seven atmospheric background stations during 2009 to 2018 in monsoon Asia (including BKT station in Indonesia, LLN and WLG stations in China, RYO and YON stations in Japan, TAP station in Republic of Korea, and UUM station in Mongolia), we analyzed the temporal and spatial variation of atmospheric CH4 concentration and its driving factors using harmonic model and maximal information-based nonparametric exploration. The results showed that the CH4 concentration in monsoon Asia varied from 1853.04 to 1935.61 nmol·mol-1, higher than that in Mauna Loa (MLO) station (1838.33 nmol·mol-1) in Hawaii, USA. The CH4 concentration decreased from north to south, with the highest value in TAP station (1935.61 nmol·mol-1) in Republic of Korea and RYO station (1907.19 nmol·mol-1) in Japan. The average seasonal amplitude at YON station in Japan was the largest (108.20 nmol·mol-1); while that at WLG station in China was the smallest (29.48 nmol·mol-1). The seasonal amplitude of TAP station in Republic of Korea changed faster at the rate of 4.49 nmol·mol-1·a-1. Except for WLG and TAP stations, CH4 concentrations were low in summer and high in winter. From the long-term perspective, the CH4 concentration at LLN (7.68 nmol·mol-1·a-1) and WLG (7.56 nmol·mol-1·a-1) stations in China exhibited the most obvious growth trend. Compared with wind speed, temperature and precipitation had greater impact on CH4 concentration, which were negatively associated with CH4 concentration. Local CH4 emission at some stations had a significant positive effect on CH4 concentration.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Poluentes Atmosféricos/análise , Ásia , China , Mongólia , República da Coreia , Estações do Ano
14.
Chemosphere ; 271: 129562, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33453481

RESUMO

Soil salinization is becoming a major threat to the sustainable development of global agriculture. Kenaf is an industrial fiber crop with high tolerance to salt stress and could be used for soil phytoremediation. However, the molecular mechanism of kenaf salt tolerance remains largely unknown. DNA methylation is an important epigenetic modifications phenomena and plays a key role in gene expression regulation under abiotic stress condition. In the present study, the kenaf seedlings were pre-treated or not with 50 µM 5-azacytidine (5-azaC, a DNA methylation inhibitor) and then subjected to different concentrations of NaCl. Results showed that the biomass and antioxidant activities (superoxide dismutase, peroxidase and catalase) of kenaf seedlings pre-treated with 5-azaC were significantly increased, while the contents of superoxide anion (O2-) and malondialdehyde (MDA) were decreased, indicating that 5-azaC pre-treatment could significantly alleviate salt stress injury. Furthermore, the methylation-sensitive amplified polymorphism (MSAP) analysis revealed that DNA methylation level of keanf seedlings pre-treated with 5-azaC significantly decreased. The expression of seven differentially methylated genes responsing to salt stress was significantly changed from real-time fluorescent quantitative (qRT-PCR) analysis. Finally, knocked-down of the l-ascorbate oxidase (L-AAO) gene by virus-induced gene silencing (VIGS) resulted in increased sensitivity of kenaf seedlings under salt stress. Overall, it was suggested that 5-azaC pre-treatment can significantly improve salt tolerance in kenaf by decreasing ROS content, raising anti-oxidant activities, and regulating DNA methylation and expression of stress-responsive genes.


Assuntos
Hibiscus , Azacitidina , Metilação de DNA , Tolerância ao Sal/genética , Estresse Fisiológico/genética
15.
Eur J Pharmacol ; 895: 173894, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476656

RESUMO

Acute myeloid leukemia (AML) is a hematopoietic disease with poor survival. Chemotherapy resistance is one of the determinant factors influencing AML prognosis. To identify genes possibly affecting the drug responses in AML, the Illumina Infinium MethylationEPIC (850K) was used to screen for differential DNA methylation loci between patients achieved complete remission (CR) or not (non-CR) after induction therapy in 37 AML patients. Then, 32 differentially methylated sites (DMS) were selected for replication in another 86 AML patients by next-generation sequencing. Nine sites including cg03988660, cg16804603, cg18166936, cg11308319, cg09095403, cg18493214, cg01443536, cg16030878 and cg10143426 were replicated. Analysis of the Gene Expression Omnibus (GEO) database showed that mRNA expression of TBC1D16 and HDAC4 was associated with AML prognosis. Methylation level of the cg16030878 in TBC1D16 3'-UTR correlated positively with TBC1D16 mRNA expression in samples both in the TCGA database and clinically collected in the study. Both higher cg16030878 methylation and higher TBC1D16 mRNA expression were associated with increased risk of non-CR and worse overall survival (OS) in AML patients. In AML cells, knockdown of TBC1D16 decreased cell proliferation and ERK phosphorylation levels, as well as increased sensitivity to mitoxantrone and decitabine indicated by IC50. In patients with combined use of decitabine, those patients with CR showed significantly lower TBC1D16 mRNA expression. On the contrary, knockdown of TBC1D16 resulted in decreased sensitivity to cytarabine in U937 cells. Our findings implicated that TBC1D16 is a potential predictor for chemosensitivity and prognosis in adult AML patients.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Ativadoras de GTPase/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Regiões 3' não Traduzidas , Adolescente , Adulto , Idoso , Proliferação de Células/efeitos dos fármacos , Metilação de DNA , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla , Células HEK293 , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Células THP-1 , Fatores de Tempo , Células U937 , Adulto Jovem
16.
Cell Death Differ ; 28(4): 1364-1378, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33188281

RESUMO

Metastatic melanoma remains a challenging disease. Understanding the molecular mechanisms how melanoma becomes metastatic is therefore of interest. Herein we show that downregulation of the AP-1 transcription factor member Fra-2 in melanoma cells is associated with an aggressive melanoma phenotype in vitro and in vivo. In vitro, Fra-2 knockdown in melanoma cells promoted cell migration and invasion associated with increased Snail-1, Twist-1/2, and matrix metalloproteinase-2 (MMP-2) expression. In vivo, Fra-2 knockdown in a melanoma cell line led to increased metastasis into the lungs and liver. The increased metastatic potential of Fra-2 knockdown melanoma cells was likely due to an accelerated cell cycle transition and increased tissue angiogenesis. Using Fra-2 knockdown cell lines microarray analysis, we identified the protein Fam212b (family with sequence similarity 212 member B) as a downstream target of Fra-2. By additional knockdown of Fam212b in Fra-2 mutant cells, we mitigated the cell migration, invasion, and cell cycle transition phenotype induced by Fra-2 knockdown. Furthermore, Fam212b overexpression enhanced ß-catenin pathway. Finally, Fam212b expression is correlated with increased melanoma metastasis and poor clinical outcomes in human patients. In summary, these findings reveal the Fra-2-Fam212b axis as a new pathway of melanoma metastasis, which can be in the future used as potential marker of the metastatic properties of melanoma.

17.
Biochem J ; 478(1): 247-260, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33346337

RESUMO

The integrity of the intestinal mucosal barrier protects hosts against pathological conditions. Early mucosal restitution after wounding refers to epithelial cell migration into a defect. The RNA-binding protein HuR plays an important role in the posttranscriptional regulation of gene expression and is involved in many aspects of cellular physiology. In the present study, we investigated the role of HuR in the regulation of cell migration through the posttranscriptional regulation of Caveolin-1 (Cav-1). Online software was used to identify Cav-1 mRNA as a potential target of HuR. The interaction of HuR with Cav-1 mRNA was investigated via ribonucleoprotein immunoprecipitation (RNP IP) assays and biotin pulldown analysis. HuR was found to bind specifically to the Cav-1 3'-UTR rather than the coding region or 5'-UTR. Transfection of cells with siHuR decreased both HuR protein levels and Cav-1 protein levels; conversely, ectopic overexpression of HuR via infection of cells with an adenoviral vector containing HuR cDNA (AdHuR) increased Cav-1 protein levels without disturbing Cav-1 mRNA levels. Thus, HuR enhanced Cav-1 expression in vitro by stimulating Cav-1 translation. Intestinal epithelium-specific HuR knockout in mice decreased Cav-1 protein levels without changing Cav-1 mRNA levels, consistent with the in vitro results. Decreasing the levels of HuR via siHuR transfection inhibited early epithelial repair, but this effect was reversed by ectopic overexpression of GFP-tagged Cav-1. These results indicate that posttranscriptional regulation of Cav-1 gene expression by HuR plays a critical role in the regulation of rapid epithelial repair after wounding.


Assuntos
Caveolina 1/metabolismo , Proteína Semelhante a ELAV 1/metabolismo , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Proteínas de Ligação a RNA/metabolismo , Regiões 3' não Traduzidas , Animais , Caveolina 1/genética , Movimento Celular , Proteína Semelhante a ELAV 1/genética , Feminino , Expressão Gênica , Regulação da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Biossíntese de Proteínas/genética , Estabilidade de RNA/genética , RNA Interferente Pequeno , Proteínas de Ligação a RNA/genética , Ratos
18.
Front Neurol ; 11: 838, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903360

RESUMO

Background: The sequence effect (SE), referring to step-to-step reduction in amplitude, is considered to lead to freezing of gait (FOG) in Parkinson's disease (PD). Visual cues may alleviate SE and help reduce freezing episodes. FOG patients show significant SE prior to turning or toward a doorway, but the SE toward a destination has not been clearly studied. Objectives: To examine the SE when approaching a destination in PD patients with FOG, and to further explore the effects of different types of visual cues on destination SE. Methods: Thirty-five PD patients were divided into a freezing (PD+FOG, n = 15) group and a non-freezing (PD-FOG, n = 20) group. Walking trials were tested under three conditions, including without cues (no-cue condition), with wearable laser lights (laser condition), and with transverse strips placed on the floor (strip condition). Kinematic data was recorded by a portable Inertial Measurement Unit (IMU) system. The destination SE and some key gait parameters were evaluated. Results: The PD+FOG group showed greater destination SE in the no-cue and laser conditions when compared to the PD-FOG group. There were no significant differences in the strip condition when comparing destination SE of the two groups. The destination SE was alleviated only by using the transverse strips on the floor. In contrast, transverse strips and wearable laser lights could increase the step length. Conclusions: The significant destination SE may explain why FOG patients are prone to freezing when heading toward their destination. Visual cues using transverse strips on the floor may be a more effective strategy for FOG rehabilitation in PD patients.

19.
Molecules ; 25(18)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32916953

RESUMO

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is the only natural vector of bacteria responsible for Huanglongbing (HLB), a worldwide destructive disease of citrus. ACP reproduces and develops only on the young leaves of its rutaceous host plants. Olfactory stimuli emitted by young leaves may play an important role in ACP control and HLB detection. In this study, volatile organic compounds (VOCs) from healthy and HLB-infected young leaves of navel orange and pomelo were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). A total of 36 compounds (including dimers or polymers) were identified and quantified from orange and 10 from pomelo leaves. Some compounds showed significant differences in signal intensity between healthy and HLB-infected leaves and may constitute possible indicators for HLB infection. Principal component analysis (PCA) clearly discriminated healthy and HLB-infected leaves in both orange and pomelo. HS-GC-IMS was an effective method to identify VOCs from leaves. This study may help develop new methods for detection of HLB or find new attractants or repellents of ACP for prevention of HLB.


Assuntos
Citrus/química , Doenças das Plantas/microbiologia , Folhas de Planta/química , Compostos Orgânicos Voláteis/análise , Animais , Bactérias , Cromatografia Gasosa , Citrus/classificação , Frutas , Hemípteros , Espectrometria de Mobilidade Iônica , Análise de Componente Principal , Software
20.
Waste Manag ; 105: 531-539, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32146414

RESUMO

Preparation of biochar from industrial solid wastes is receiving increasing attention in recent years. In this paper, alkaline protease, neutral protease and collagenolytic protease are used in preliminary steps of leather production, which are expected to replace the traditional chemical agents while preserving quality of the finished leather. The protease application has remarkable positive influence towards characteristics of biochar prepared by collagen-containing solid wastes produced in preliminary steps. The enzymatic action time should be more than 3 h for complete permeation and catalysis, and the diameters of treated collagen fibers were in the range of 10 to 20 nm. The micro-cracks occurring on collagen fibers would have an obviously impact on the formation of biochar. The application of proteases reduce the pollution of traditional production through replacing traditional polluted chemicals, and the characteristics of biochars are obviously improved with good surface area and high carbon content approximately 70%. Its surface area can reach 967 m2/g. These biochars contain oxygen-containing functional groups, and the oxygen content of biochars are all over 20%. The enzyme application in leather production are effective to the properties of biochars prepared by collagen-containing solid wastes. This research can serve as a basis for the preparation of biochar derived from of natural bio-wastes thereby promoting the development of biomaterials.


Assuntos
Carvão Vegetal , Resíduos Sólidos , Colágeno , Peptídeo Hidrolases
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