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1.
Dev Neurosci ; : 1-10, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37757768

RESUMO

Glioblastoma (GBM) is the most prevalent and fatal form of brain tumor, which is associated with a poor prognosis. ATP-binding cassette subfamily F member 1 (ABCF1) is an E2 ubiquitin-conjugating enzyme, which is implicated in regulating immune responses and tumorigenesis. Aberrant E3 ubiquitylation has been evidenced in GBM. However, the role of ABCF1 in GBM needs to be further explored. The expression of ABCF1, CXC chemokine ligand 12 (CXCL12), and CXC chemokine receptor 4 (CXCR4) in GBM tissues was examined by the GEPIA tool, real-time PCR and Western blotting. HMC3, U251MG, and LN-229 cells were cultured and transfected with shRNA targeting ABCF1 and ABCF1 plasmids. The proliferative, migrative, and invasive ability of cells was detected. Western blotting was used to detect the levels of phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (AKT). We observed that GBM tissues had higher ABCF1, CXCL12, and CXCR4 expression levels. The expression levels of CXCL12 and CXCR4 were enhanced by ABCF1 overexpression, which were significantly reversed by silence of ABCF1 in GBM cells. Silencing ABCF1 or CXCR4 inhibition weakened the capacity of GBM cell growth, migration, and invasion, while ectopic ABCF1 expression or CXCL12 treatment enhanced the cellular function of GBM cells. Furthermore, p-PI3K and p-AKT protein levels were downregulated by ABCF1 knockdown or CXCR4 blockade, which were prompted by ABCF1 overexpression or CXCL12 supplement. The ABCF1-CXCL12-CXCR4 axis was identified as a key player in GBM cell survival and metastasis by activating the PI3K/AKT signaling pathway in GBM cells.

2.
Cell Mol Biol (Noisy-le-grand) ; 69(1): 131-136, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37213145

RESUMO

To analyze the application effect of anti-tuberculosis therapy (ATT) combined with all-in-one nursing care on pulmonary tuberculosis (PT). Seventy-four PT patients who received ATT in our hospital between December 2015 and June 2016 were selected as the research participants and randomized into a research group (RG; n=37) and a control group (CG; n=37) that were given all-in-one nursing care and routine care, respectively. The cure rate and treatment compliance were compared between groups, and the awareness of disease prevention and treatment was investigated. Patients' psychological status and quality of life were evaluated using the Self-Rating Depression/Anxiety Scale (SAS/SDS) and the Quality of Life Questionnaire Core 30 (QLQ-C30), respectively. RG and CG were not statistically different in the clinical cure rate (P>0.05), but the X-ray cure rate was higher and the recurrence rate was lower in RG (P<0.05). In addition, RG showed higher medication compliance rate, regular reexamination rate and awareness of disease prevention and treatment than CG (P<0.05). Reductions in SAS/SDS scores were observed in both groups after care, with even lower levels in RG, while the QLQ-C30 score increased and was higher in RG as compared to CG (P<0.05). Therefore, All-in-one nursing care can effectively enhance the level of treatment compliance and awareness of disease prevention and treatment of PT patients. In the future, when treating PT patients in the clinic, the effectiveness of ATT can be improved by implementing all-in-one nursing care to provide more reliable prognosis for patients.


Assuntos
Tuberculose Pulmonar , Tuberculose , Humanos , Antituberculosos/uso terapêutico , Inflamação , Qualidade de Vida , Tuberculose Pulmonar/tratamento farmacológico
3.
Sensors (Basel) ; 23(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37571492

RESUMO

Driving behavior recognition can provide an important reference for the intelligent vehicle industry and probe vehicle-based traffic estimation. The identification of driving behavior using mobile sensing techniques such as smartphone- and vehicle-mounted terminals has gained significant attention in recent years. The present work proposed the monitoring of longitudinal driving behavior using a machine learning approach with the support of an on-board unit (OBU). Specifically, based on velocity, three-axis acceleration and three-axis angular velocity data were collected by a mobile vehicle terminal OBU; through the process of data preprocessing and feature extraction, seven machine learning algorithms, including support vector machine (SVM), random forest (RF), k-nearest neighbor algorithm (KNN), logistic regression (LR), BP neural network (BPNN), decision tree (DT), and the Naive Bayes (NB), were applied to implement the classification and monitoring of the longitudinal driving behavior of probe vehicles. The results show that the three classifiers SVM, RF and DT achieved good performances in identifying different longitudinal driving behaviors. The outcome of the present work could contribute to the fields of traffic management and traffic safety, providing important support for the realization of intelligent transport systems and the improvement of driving safety.

4.
Int J Environ Health Res ; 33(4): 337-347, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35098822

RESUMO

This study explored the association of exposure to air pollutants during gestational and the first year of life with physical growth in preschoolers. The linear and logistic regression models were used to estimate the associations between air pollution and childhood growth. After adjusting for confounders, z-scores of body mass index (zBMI, and 95% confidence intervals, 95%CI) increased by 1.164(1.054,1.285), 1.136(1.050,1.228) and 1.165(1.041,1.303), associated with per interquartile range (IQR) increase in NO2 (nitrogen dioxide), PM2.5 and PM10 (particulate matter with aerodynamic diameters ≤2.5 µm and 10 µm) during gestational, respectively. The odds ratios (and 95%CI) of childhood overweight/obesity associated with per IQR increase in NO2, PM2.5 and PM10 during gestational were 1.425(1.168,1.737), 1.255(1.087,1.450) and 1.332(1.104,1.605). Positive associations were found between air pollution during the first year of life and zBMI or overweight/obesity. Our findings suggest exposure to air pollution were associated with childhood growth, and improving air quality is beneficial for childhood growth.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Dióxido de Nitrogênio/análise , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Obesidade , Sobrepeso , Exposição Ambiental/análise , China
5.
Can J Microbiol ; 68(7): 483-492, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35344674

RESUMO

Numerous studies have reported the dynamics of microbes when biochar was applied, whereas the information on the alterations of bacterial community after application of rapeseed straw-derived biochar is limited. A pot experiment with two rapeseed straw-derived biochar application treatments (with biochar application at the rate of 200 g/pot, C1, and without biochar application, 0 g/pot, C0) was conducted. No significant differences were observed in the number of operational taxonomic units, observed species, Shannon index, Simpson index, Chao1, ACE, and phylogenetic diversity whole tree between the C1 and C0 treatments. Taxonomic analysis at the phylum level showed that the abundances of Bacteroidetes and Parcubacteria were higher in the C1 treatment compared to the C0 treatment, while Acidobacteria, Chloroflexi, Rokubacteria, Berkelbacteria, and Latescibacteria were observed with higher abundance in the C0 treatment compared to the C1 treatment. Taxonomic analysis at the genus level showed that the abundances of Gracilibacter, Lentimicrobium, unidentified Rikenellaceae, Hydrogenophaga, and Bacillus were higher in the C1 treatment compared to the C0 treatment, while Candidatus Solibacter, Candidatus Koribacter, and Lutispora abundances were found to be higher in the C0 treatment compared to the C1 treatment. Obvious clusters were observed between the C1 and C0 treatments in both principal component analysis and nonmetric multidimensional scaling. These results indicate that soil bacterial community was altered after rapeseed straw-derived biochar was applied.


Assuntos
Brassica napus , Oryza , Bactérias/genética , Carvão Vegetal , Filogenia , Solo/química , Microbiologia do Solo
6.
Sensors (Basel) ; 21(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34451061

RESUMO

The advantages of UAV video in flexibility, traceability, easy-operation, and abundant information make it a popular and powerful aerial tool applied in traffic monitoring in recent years. This paper proposed a systematic approach to detect and track vehicles based on the YOLO v3 model and the deep SORT algorithm for further extracting key traffic parameters. A field experiment was implemented to provide data for model training and validation to ensure the accuracy of the proposed approach. In the experiment, 5400 frame images and 1192 speed points were collected from two test vehicles equipped with high-precision GNSS-RTK and onboard OBD after completion of seven experimental groups with a different height (150 m to 500 m) and operating speed (40 km/h to 90 km/h). The results indicate that the proposed approach exhibits strong robustness and reliability, due to the 90.88% accuracy of object detection and 98.9% precision of tracking vehicle. Moreover, the absolute and relative error of extracted speed falls within ±3 km/h and 2%, respectively. The overall accuracy of the extracted parameters reaches up to 98%.

7.
Crit Rev Eukaryot Gene Expr ; 30(4): 349-357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32894664

RESUMO

Multiple myeloma (MM) is one of the most common malignancies, and the clinical outcome of patients with MM remains poor. Our objective is to screen biomarkers correlated with clinicopathological features and survival of patients with MM. A gene co-expression network was constructed to screen hub genes related to the three stages in the International Staging System (ISS) of MM. Functional analysis and protein-protein interaction analysis of the hub genes was performed. CHEK1, a gene most related to the ISS stages of MM, was selected for further clinical validation. A total of 780 hub genes correlated with ISS stages of MM were identified. Functional enrichment analysis of hub genes suggested that these genes were mostly enriched in several gene ontology (GO) terms and pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) that were involved in cell proliferation and immune response. Expression of the gene for the protein checkpoint kinase I (CHEK1) was increased in MM cells from newly diagnosed patients (P = 0.0304) and relapsed patients (P = 0.0002) as compared to normal plasma cells. Meanwhile, CHEK1 was increased more in MM patients with stage II disease (P = 0.0321) and stage III disease (P = 0.0076) than in those with stage I disease. Survival analysis indicated that MM patients in the group characterized by low CHEK1 expression were associated with better clinical outcomes in terms of time to progression, event-free survival, and overall survival. High expression of CHEK1 predicted poor clinical characteristics of MM patient, and our results indicate that it can be considered a biomarker for the diagnosis of MM.


Assuntos
Quinase 1 do Ponto de Checagem/genética , Mieloma Múltiplo/genética , Biomarcadores Tumorais/genética , Humanos , Mieloma Múltiplo/patologia , Análise de Sobrevida
8.
Phys Chem Chem Phys ; 22(18): 10305-10313, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32356552

RESUMO

Transition metal modified molybdenum disulfide to improve the performance of photocatalytic reduction of carbon dioxide has been receiving much attention. Herein, a novel high-efficiency photocatalytic composite Ag/2H-MoS2 has been constructed and simulated using density functional theory (DFT) for unveiling the mechanism of improved photocatalytic reduction of CO2 in our experimental research. Our calculations about the band structure and electronic and optical properties indicate that the loading of Ag atoms enhances the photocatalytic performance of 2H-MoS2 nanosheets by transferring the photogenerated electrons from the valence band of 2H-MoS2 to the loaded Ag atoms. Furthermore, 20 wt% Ag loaded 2H-MoS2 is the most suitable for the thermodynamic requirement of reducing CO2 to CH4 among the catalysts with different Ag loadings, and the formation of *CHO in 20 wt% Ag/2H-MoS2 is the potential-determining step, whose Gibbs free energy reduces from 2.830 eV of 2H-MoS2 to 0.925 eV. Meanwhile the thermochemical results predict the best path for reducing CO2 on such a photocatalyst as CO2 → *COOH → *CO → *CHO → *CH2O → *OCH3 → *CH3OH → CH4. The photocatalytic performance of pristine 2H-MoS2 in CO2 reduction is therefore significantly improved by loading silver. This research provides a theoretical reference for transition metal modified 2H-MoS2 nanosheets.

9.
J Cell Biochem ; 120(6): 9724-9736, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30582214

RESUMO

OBJECTIVES: Adamantinomatous craniopharyngiomas (adaCP) accounts for 5.6% to 15% of intracranial tumors. High expression of chemokine (C-X-C motif) ligand 12 (CXCL12, also known as stromal cell-derived factor 1 [SDF1]) and its receptor CXC receptor type 4 (CXCR4) are widespread in various malignancy via multiple signal transduction pathways. This study aims to investigate the mechanism of CXCL12/CXCR4 promoting proliferation, migration, and invasion of adaCP. METHODS: Quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry were used to evaluate the expression of CXCL12/CXCR4 mRNA and protein in 10 human adaCP tissues. Three successfully primary cell lines were obtained from native mainly solid tumor specimens, and confirmed by the means of inverted contrast microscope directly and following hematoxylin and eosin staining. Immunofluorescence was used to detect protein expression in vivo for the verification of primary cell line. Proliferation, migration, and invasion assays were performed to assess the biological functional role of CXCL12/CXCR4 in adaCP. The signal pathways involved in the action of CXCL12/CXCR4 in adaCP were also evaluated. RESULTS: CXCL12 and CXCR4 were highly expressed in human adaCP samples. Primary adaCP cells were isolated and detected by the means of immunofluorescence for the detection of pan cytokeratin (pan-CK) and vimentin (VIM). Overexpression of CXCL12/CXCR4 significantly promoted the proliferation, migration, and invasion of primary adaCP cells. Moreover, cancer-promoting activity of CXCL12/CXCR4 is partially through its facilitation of PI3K/AKT signal pathway. CONCLUSIONS: Our data showed that CXCL12/CXCR4 promotes adaCP proliferation, migration, and invasion through PI3K/AKT signal pathway. These findings suggested that therapeutic strategies regulating CXCL12/CXCR4 expression may provide an effective treatment of adaCP.


Assuntos
Movimento Celular , Proliferação de Células , Quimiocina CXCL12/metabolismo , Craniofaringioma/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Hipofisárias/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais , Craniofaringioma/patologia , Humanos , Invasividade Neoplásica , Neoplasias Hipofisárias/patologia
10.
Bioorg Med Chem Lett ; 29(20): 126673, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31519373

RESUMO

A series of benzothiazoles with a cyano group was synthesized and evaluated as endothelial lipase (EL) inhibitors for the potential treatment of cardiovascular diseases. Efforts to reduce molecular weight and polarity in the series led to improved physicochemical properties of these compounds, as well as selectivity for EL over hepatic lipase (HL). As a benchmark compound, 8i demonstrated potent EL activity, an acceptable absorption, distribution, metabolism and elimination (ADME) profile and pharmacokinetic (PK) exposure which allowed further evaluation in preclinical animal efficacy studies.


Assuntos
Benzotiazóis/química , Doenças Cardiovasculares/tratamento farmacológico , Inibidores Enzimáticos/química , Lipase/antagonistas & inibidores , Animais , Benzotiazóis/farmacologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lipase/genética , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
11.
Bioorg Med Chem Lett ; 29(15): 1918-1921, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31176700

RESUMO

A low level of high density lipoprotein (HDL) is an independent risk factor for cardiovascular disease. HDL reduces inflammation and plays a central role in reverse cholesterol transport, where cholesterol is removed from peripheral tissues and atherosclerotic plaque. One approach to increase plasma HDL is through inhibition of endothelial lipase (EL). EL hydrolyzes phospholipids in HDL resulting in reduction of plasma HDL. A series of benzothiazole sulfone amides was optimized for EL inhibition potency, lipase selectivity and improved pharmacokinetic profile leading to the identification of Compound 32. Compound 32 was evaluated in a mouse pharmacodynamic model and found to show no effect on HDL cholesterol level despite achieving targeted plasma exposure (Ctrough > 15 fold over mouse plasma EL IC50 over 4 days).

12.
Anal Chem ; 90(14): 8592-8599, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-29939012

RESUMO

Ionic current rectification (ICR) phenomena within dual glass pipettes are investigated for the first time. We demonstrate that the ionic flow presents different behaviors in dual nano- and micropipettes when the two channels are filled with the same electrolyte KCl and hung in air. Bare dual nanopipettes cannot rectify the ionic current because of their geometric symmetry, but the ICR can be directly observed based on bare dual micropipettes. The phenomena based on dual micropipettes could be explained by the simulation of the Poisson-Nernst-Plank equation. After modification with different approaches, the dual nanopipettes have asymmetric charge patterns and show various ICR behaviors. They have been successfully employed to fabricate various nanodevices, such as ionic diodes and bipolar junction transistors. Due to the simple and fast fabrication with high reproducibility, these dual pipettes can provide a novel platform for controlling ionic flow in nano- and microfluidics, fabrication of novel nanodevices, and detection of biomolecules.

13.
Opt Express ; 26(9): 11250-11264, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29716049

RESUMO

This work presents a novel nondestructive cavity pressure characterization approach in microinjection molding (µIM) through measuring 3D part thickness distributions. For this purpose, a plano lens was designed and experiments based on Taguchi method were conducted. Both overall and local lens thickness distributions under various process conditions were analyzed in terms of their relevance with the cavity pressure during molding. Unexpectedly, a reliable linear regression model was developed fulfilling nondestructive multi-point or even continuous cavity pressure characterization with the overall lens thickness distribution. Furthermore, the topography of the constructed 3D thickness surface was found to depend on both process condition and measuring position. Finally, the process conditions were optimized for obtaining uniform distributions of both 3D thickness and cavity pressure.

14.
Langmuir ; 34(26): 7738-7743, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29806943

RESUMO

Monodisperse patchy silica nanoparticles (PSNPs) less than 100 nm are prepared based on the seed-regrowth method using a poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO)-PEO-type block copolymer as a surface modifier. Well-defined patches are controllably synthesized through area-selective deposition of silica onto the surface of seeds. After colloidal PSNPs are further modified with trimethylchlorosilane, the advancing and receding contact angles of water for PSNPs are 168 ± 2° and 167 ± 2°, respectively. The superhydrophobic and transparent coatings on the various types of substrates are obtained by a simple drop-casting procedure. Additionally, almost the same superhydrophobicity can be achieved by using colloidal PSNPs via redispersing the powder of superhydrophobic PSNPs in ethanol.

15.
Med Sci Monit ; 24: 3113-3118, 2018 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-29752880

RESUMO

BACKGROUND The present study aimed to investigate the clinical relevance of fragile histidine triad protein (FHIT) in patients with bladder cancer (BC). MATERIAL AND METHODS Three independent BC microarray studies were collected and reanalyzed. The expression of FHIT was evaluated between BC samples and normal bladder tissues. The correlation between the expression of FHIT and clinicopathological features was analyzed using the chi-square test. Log-rank based survival analysis was conducted to detect the survival significance of FHIT in patients with BC. Gene set enrichment analysis (GSEA) was performed to identify the mechanisms. RESULTS FHIT was significantly downregulated in BC cells (p=0.0044). BC patients in the FHIT high expression group had better clinical characteristics (including invasiveness, tumor grade, disease progression, and T staging) than those in the FHIT low expression group (p<0.0001, p<0.0001, p=0.031, p<0.0001, and p=0.056, respectively). Patients in the FHIT high expression group had better cancer-specific survival (p<0.0001) and overall survival (p=0.0008) than those in the FHIT low expression. GSEA results indicated that BC samples in the FHIT low expression group were enriched in interferon alpha response, apoptosis, androgen response, interferon gamma response, heme metabolism, and transforming growth facto r(TGF) beta signaling. CONCLUSIONS FHIT predicts better clinical relevance for patients with BC, which may be a promising therapeutic target.


Assuntos
Hidrolases Anidrido Ácido/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Hidrolases Anidrido Ácido/genética , Neoplasias da Mama/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Análise de Sobrevida , Neoplasias da Bexiga Urinária/genética
16.
J Nanosci Nanotechnol ; 17(4): 2438-446, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-29648748

RESUMO

Nanosheet and hierarchical microsphere nanostructures of ZnFe2O4­BiOCl nanocomposites with various ZnFe2O4 contents were prepared through hydrothermal deposition method. The morphology and structure of the as-prepared samples were systematically characterized by field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, UV-vis diffuse reflectance spectroscopy, Brunauer-Emmert-Teller method, and photoluminescence spectra. The photocatalytic activities of the two different shapes of ZnFe2O4­BiOCl composites have been evaluated by photocatalytic reduction of CO2 in cyclohexanol under UV light irradiation. The results showed that cyclohexanol was oxidized to cyclohexanone (CH), and CO2 was reduced and then reacted with cyclohexanol to produce cyclohexyl formate (CF). The ZnFe2O4­BiOCl composites with different shapes showed much higher CF and CH yields than those of pristine BiOCl and mechanically mixed samples, respectively. When the ZnFe2O4 content in the composites reached 9%, two different shapes of ZnFe2O­BiOCl composites both achieved the highest photocatalytic activities. In contrast, the activities for photocatalytic reduction of CO2 in cyclohexanol over hierarchical microsphere ZnFe2O4­BiOCl composites were higher than those of nanosheet structure samples. The higher activities over hierarchical microsphere composites could be attributed to its unique hierarchical structure, large illumination area, and low Photoluminescence (PL) emission intensity, which were beneficial for the separation of photogenerated charge carriers. This work provided a novel approach for the design and construction of highly efficient photocatalyst and reaction system for photoreduction of CO2.

17.
Nurs Health Sci ; 19(4): 403-413, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28730735

RESUMO

In this systematic review and meta-analysis, we evaluated the effectiveness, safety and comfort of StatLock for the securement of peripherally-inserted central catheters. PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, WanFang Database, and China Science and Technology Journal Database were searched. Randomized, controlled trials comparing StatLock with tape or suture on the performance of securing peripherally-inserted central catheters were selected. Meta-analysis was performed using Review Manager 5.3 software. Thirteen randomized, controlled trials involving 1970 patients were included. Our results showed that StatLock reduced the incidence of catheter dislodgement and unplanned removal. Moreover, patients in the StatLock group had lower incidence of skin ulceration, phlebitis, catheter-related bloodstream infection, and cellulitis, and felt more comfortable compared with those in the control group. Current evidence suggests that the StatLock securement device offer advantages over tape and suture in preventing catheter-related complications and improving patient comfort. However, as considerable heterogeneity was found among the included studies, and the quality of evidence for main outcomes was relatively low, the results should be viewed with caution.


Assuntos
Cateterismo Venoso Central/instrumentação , Cateterismo Periférico/instrumentação , Desenho de Equipamento/normas , Segurança de Equipamentos/normas , China , Humanos , Complicações Pós-Operatórias/prevenção & controle
18.
J Cell Mol Med ; 20(5): 769-81, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26929182

RESUMO

Glucose is the major energy supply and a critical metabolite for most cells and is especially important when cell is differentiating. High or low concentrations of glucose enhances or inhibits the osteogenic, chondrogenic and adipogenic differentiation of cell via the insulin, transforming growth factor-ß and peroxisome proliferator-activated receptor γ pathways, among others. New evidence implicates the hexosamine biosynthetic pathway as a mediator of crosstalk between glucose flux, cellular signalling and epigenetic regulation of cell differentiation. Extracellular glucose flux alters intracellular O-GlcNAcylation levels through the hexosamine biosynthetic pathway. Signalling molecules that are important for cell differentiation, including protein kinase C, extracellular signal-regulated kinase, Runx2, CCAAT/enhancer-binding proteins, are modified by O-GlcNAcylation. Thus, O-GlcNAcylation markedly alters cell fate during differentiation via the post-transcriptional modification of proteins. Furthermore, O-GlcNAcylation and phosphorylation show complex interactions during cell differentiation: they can either non-competitively occupy different sites on a substrate or competitively occupy a single site or proximal sites. Therefore, the influence of glucose on cell differentiation via O-GlcNAcylation offers a potential target for controlling tissue homoeostasis and regeneration in ageing and disease. Here, we review recent progress establishing an emerging relationship among glucose concentration, O-GlcNAcylation levels and cell differentiation.


Assuntos
Acetilglucosamina/metabolismo , Epigênese Genética , Glucose/metabolismo , Células-Tronco Mesenquimais/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Processamento de Proteína Pós-Traducional , Acilação , Adipócitos/citologia , Adipócitos/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Diferenciação Celular , Condrócitos/citologia , Condrócitos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , N-Acetilglucosaminiltransferases/genética , Osteoblastos/citologia , Osteoblastos/metabolismo , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Transdução de Sinais
19.
Bioorg Med Chem Lett ; 26(14): 3278-3281, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27256912

RESUMO

Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice.


Assuntos
Aminas/farmacologia , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Descoberta de Drogas , Aminas/síntese química , Aminas/química , Animais , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Relação Dose-Resposta a Droga , Humanos , Camundongos , Camundongos Transgênicos , Estrutura Molecular , Relação Estrutura-Atividade
20.
Anal Chem ; 87(17): 9070-7, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26218167

RESUMO

The study of behaviors of ionic current rectification (ICR) in organic solutions with quartz nanopipettes is reported. ICR can be observed even in organic solutions using quartz pipettes with diameters varied from several to dozens of nanometers, and the direction of ICR is quite different from the ICR observed in aqueous phase. The influences of pore size, electrolyte concentration, and surface charge on the ICR have been investigated carefully. Water in organic solutions affects the direction and extent of ICR significantly. Mechanisms about the formation of an electrical double layer (EDL) on silica in organic solutions with different amount of water have been proposed. An improved method, which can be employed to detect trace water in organic solutions, has been implemented based on Au ultramicroelectrodes with cathodic differential pulse stripping voltammetry.

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