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1.
Life Sci ; 248: 117469, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32109485

RESUMO

AIMS: Histone deacetylases inhibitors have shown favorable antitumor activity in clinical investigations. In the present study, we assessed the effects of a novel hydroxamic acid-based HDAC inhibitor, SB939, on breast cancer metastasis and tumor growth and characterized the underlying molecular mechanisms. MAIN METHODS: MTS, Wound-healing, and Transwell chamber invasion assays were used to detect the inhibition effects of SB939 on proliferation, migration, and invasion of breast cancer cells. Western blot, cellular immunofluorescence, and EMSA were used to explore the molecular mechanism of SB939 in suppressing breast cancer metastasis. MDA-MB-231 subcutaneous tumor-bearing model of nude mice and the spontaneous metastasis model of breast cancer were both applied to verify in vivo anti-tumor growth and anti-metastatic effects. KEY FINDINGS: Our results demonstrated that SB939 at 0.5-1 µmol/L markedly impaired the chemotactic motility of breast cancer cells. SB939 reversed epithelial-mesenchymal transition (EMT) process, as evidenced by upregulation E-cadherin expression and downregulation expressions of N-cadherin and vimentin through increasing the levels of ac-histone H3 and H4 and drecreasing the expressiongs of HDAC 5 and 4. This cascade inhibition mediated by SB939 was well interpreted by inactivating phosphorylation of STAT3, blocking its DNA-binding activity, and decreasing the expressions of STAT3-dependent target genes, including MMP2 and MMP9. Furhtermore, we found that SB939 significantly inhibited breast cancer metastasis and tumor growth in vivo and showed superior anti-tumor properties compared with SAHA in two breast cancer animal models. SIGNIFICANCE: Our findings indicate that SB939 may be an effective therapeutic option for treating advanced breast cancer.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Neoplasias da Mama/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Inibidores de Histona Desacetilases/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Vimentina/genética , Vimentina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Ultrasonics ; 103: 106105, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32044565

RESUMO

Although Rayleigh waves are a research topic of constant interest, research on Rayleigh waves in flexoelectric materials is still lacking. This study reports the influences of flexoelectricity, strain gradient elasticity, micro-inertia effect and surface effect on Rayleigh waves in a homogeneous centrosymmetric flexoelectric material half-space. The nonclassical governing equations and boundary conditions are deduced with Hamilton's principle. Our findings suggest that the influence of flexoelectricity on the phase velocity depends on the flexoelectric coefficients. Strain gradient elasticity and surface elasticity can increase the phase velocity, while micro-inertia effect can decrease the phase velocity. Besides, these influences become significant for Rayleigh waves with high frequencies and short wavelengths. A mathematical foundation may be established to measure the material properties on the basis of the relationships among the material parameters, the phase velocity and the wave number. Moreover, the current work might provide guidance in developing small-scale acoustic wave devices operating at high frequencies.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32103429

RESUMO

The use of Napier grass to remediate heavy metal-contaminated soil is a new phytoremediation technique. The objective of this study was to evaluate the ability of Napier grass (Pennisetum purpureum Schumach.) to remediate Cd- and Zn-contaminated cultivated soil under nonmowing and mowing and the possibility of safe utilization of the stem and leaf after detoxification by liquid extraction. Three Napier grass varieties, P. purpureum cv. Mott (PM), P. purpureum cv. Red (PR), and P. purpureum cv. Guiminyin (PG), were planted in a field with 3.74 mg kg-1 Cd and 321.26 mg kg-1 Zn for 180 days. The maximum amounts of Cd and Zn removed by PG were 197.5 and 5023.9 g ha-1, respectively, almost equaling those of hyperaccumulators. Compared with nonmowing, mowing did not decrease the Cd and Zn contents in various tissues but increased the biomasses of PM, PR, and PG by 86.6%, 18.9%, and 26.1%, respectively. Compared with nonmowing, the amounts of Cd removed by PM, PR, and PG under mowing increased by 110.5%, 40.0%, and 107.9%, respectively, and that of Zn increased by 63.0%, 53.1%, and 71.6%. The dominant Cd and Zn chemical fractions in Napier grass were the pectate- and protein-integrated fractions. After liquid extraction, although the nutrient element (Ca, K, Mg, and Mn) contents in the stem and leaf were reduced significantly, the Cd and Zn contents decreased below the limit of the Chinese Hygienic Standard for Feeds, and the crude protein content was largely retained. Such detoxified stems and leaves can be safely used as feeds or as raw materials for energy production.

4.
Environ Pollut ; 260: 113970, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-32014742

RESUMO

Nano-Fe3O4-modified biochar (BC-Fe) was prepared by the coprecipitation of nano-Fe3O4 on a rice husk biochar surface. The effects of BC-Fe on cadmium (Cd) bioavailability in soil and on Cd accumulation and translocation in rice (Oryza sativa L. cv. 'H You 518') were investigated in a pot experiment with 7 application rates (0.05-1.6%, w/w). BC-Fe increased the biomass of the rice plants except for the roots and affected the concentration and accumulation of Cd and Fe in the plants. The Cd concentrations of brown rice were significantly decreased by 48.9%, 35.6%, and 46.5% by the 0.05%, 0.2%, and 0.4% BC-Fe treatments, respectively. Soil cation exchange capacity (CEC) increased by 9.4%-164.1% in response to the application of BC-Fe (0.05-1.6%), while the soil Cd availability decreased by 6.81%-25.0%. However, 0.8-1.6% BC-Fe treatments promoted Cd transport to leaves, which could increase the risk of Cd accumulation in brown rice. Furthermore, BC-Fe application promoted the formation of iron plaque and enhanced the root interception of Cd. The formation of iron plaque reduced the toxicity of Cd to rice roots, but this barrier effect was limited and had an interval threshold (DCB-Fe: 22.5-27.3 g·kg-1) under BC-Fe treatments.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32100214

RESUMO

To investigate the differences in cadmium (Cd) and lead (Pb) uptake and translocation among rape cultivars and genotypes and select suitable rape cultivars for both safe production and soil remediation, a field experiment was carried out with 39 rape cultivars of three genotypes on a farmland polluted with Cd and Pb in eastern Hunan Province, China. The Cd and Pb contents in rape tissues were measured, and the amount of Cd and Pb removed was calculated. The results showed that Cd in rape plants accumulated mostly in stems, while Pb accumulated mostly in roots. The Cd accumulation in various rape tissues followed the sequence stem > root > husk > rapeseed, while the Pb accumulation followed the sequence root > stem > husk > rapeseed. The total Cd and Pb removed by planting rape were 4.50-23.6 g ha-1 and 5.85-13.7 g ha-1, respectively, and the Cd and Pb contents in rapeseeds were in the range 0.11-0.47 mg kg-1 and 0.03-0.84 mg kg-1, respectively. Only the Pb content in rapeseed of "Youyan 9" exceeded the limit of the maximum levels of contaminants in foods (GB2762-2017, Pb ≤ 0.2 mg kg-1). In this experiment, the roots of most rape cultivars showed a greater capacity for Cd transport, while the stems showed a greater capacity for Pb transport. Except for the TFstem-husk for Cd, there were no significant differences in the TFs and BAFs of 39 rape cultivars, and clear variations in Cd content were found in the stems of the three genotypes, while there was no significant difference in the Cd and Pb contents in the other tissues. In the farmland polluted with Cd and Pb, planting "Xiangzayou 695" and "Youyan 2013" not only reduced soil pollution but also allowed the production of safe rapeseed.

6.
Oral Dis ; 26(3): 547-557, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31926047

RESUMO

CD44, a cell-surface glycoprotein, functions as a receptor for hyaluronic acid. Our research group has previously shown that CD44 is a biomarker for the CD44hi cells (tumor-initiating cells; TICs) in murine salivary gland tumors. However, little is known concerning the biological roles of CD44 in the tumorigenesis of pleomorphic adenoma. The present study is aimed to investigate the effects of CD44 on the proliferation, invasive capability, and apoptosis of TICs in vitro, as well as the tumorigenicity of TICs in vivo. The results demonstrated that knockdown of CD44 attenuated the malignant phenotype of TICs. Furthermore, in vivo xenograft studies indicated that CD44 knockdown inhibited tumorigenesis of pleomorphic adenoma. In addition, neither the CD44low cells nor the CD44-modified CD44low cells developed neo-tumors, which indicated that overexpression of CD44 did not enable the CD44low cells to be transformed into TICs. Taken together, these data demonstrate that CD44 not only acts as a biomarker, but also functions as a key player in the tumor-initiating capacity of TICs. These results shed light on the pathogenesis of salivary gland tumors and provide a potential therapeutic target for treating pleomorphic adenoma.

7.
Naunyn Schmiedebergs Arch Pharmacol ; 393(1): 67-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31420721

RESUMO

NLRP3 inflammasome is a key contributor to obesity-related insulin resistance and type 2 diabetes (T2D). Adenosine monophosphate-activated protein kinase (AMPK) is a principle intracellular energy sensor exerting protective effect against T2D. Strikingly, compound C, an inhibitor of AMPK, considerably inhibited the secretion of IL-1ß when THP-1 cells were stimulated with LPS plus palmitic acid (PA). The underlying mechanism was examined with respect to the effect of compound C on NLRP3 inflammasome, a multiprotein complex which controls the processing and production of IL-1ß. Interestingly, compound C significantly attenuated the activation of NLRP3 inflammasome. This phenomenon was reproduced in AMPK siRNA-transfected THP-1 cells, indicating that compound C exerts this function despite AMPK knockdown. Also, it significantly suppresses the mitochondria-generated reactive oxygen species (ROS) required for NLRP3 inflammasome activation. In conclusion, compound C was shown to significantly attenuate the NLRP3 inflammasome despite AMPK knockdown, rendering it as the novel target of compound C. Potentially, compound C attenuates NLRP3 inflammasome through the suppression of mitochondrial ROS production. These findings offer initial evidence into compound C as a novel pharmacological agent with significant therapeutic potential in NLRP3 inflammasome-related disorders, including obesity, insulin resistance, and T2D. Thus, further studies are essential to identify the effect of compound C on these diseases in vitro.

8.
Sci Total Environ ; 704: 134883, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31780178

RESUMO

Heavy metal contamination in surface water of the Three Gorges Reservoir (TGR) is a distinctly important issue for the water security of the Yangtze River Basin in China. Surface water samples of 46 river sections in the main stream and tributaries of the entire TGR area were collected during high and low water level operation periods of 2015 to 2016 to investigate the spatial-temporal distribution characteristics of six heavy metals (As, Cd, Cr, Cu, Pb and Zn) and assess their health risks. Results indicated that average concentrations of heavy metals in the surface water were lower than the threshold values for the first-grade water quality based on the Chinese standard of GB3838-2002 except for Zn. Heavy metals concentrations at high water levels was slightly lower compared with that at the low water levels in the main stream, As, Cd, Cr and Cu exhibited certain inter-annual decline variations in 2015 and 2016. Heavy metals showed distinctly regional variation and mainly distributed in upstream urban sections of the TGR area. The total health risks caused by heavy metals at the low water level periods, most of which exceeded the maximum acceptable risk level recommended by ICRP (5×10-5 a-1), were slightly higher than that at the high water level periods. The average annual health risks caused by carcinogenic and non-carcinogenic heavy metals was ranked as Cr > As > Cd > Pb > Cu > Zn, meanwhile this value via drinking water ingestion was 2 to 3 orders of magnitude larger than that of dermal contact. Carcinogenic heavy metals of Cr and As were the main causes of health risk and should be prioritized as the main focus of aquatic environment risk management in the TGR area.


Assuntos
Monitoramento Ambiental , Metais Pesados/análise , Poluentes Químicos da Água/análise , Poluição Química da Água/estatística & dados numéricos , China , Humanos , Medição de Risco , Qualidade da Água
9.
Angew Chem Int Ed Engl ; 59(1): 161-166, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31639258

RESUMO

An umpolung 1,4-addition of aryl iodides to enals promoted by cooperative (terpy)Pd/NHC catalysis was developed that generates various bioactive ß,ß-diaryl propanoate derivatives. This system is not only the first reported palladium-catalyzed arylation of NHC-bound homoenolates but also expands the scope of NHC-induced umpolung transformations. A diverse array of functional groups such as esters, nitriles, alcohols, and heterocycles are tolerated under the mild conditions. This method also circumvents the use of moisture-sensitive organometallic reagents.

10.
Biotechnol Lett ; 42(2): 197-207, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786685

RESUMO

OBJECTIVES: Although abnormal expression of early growth response-1 (Egr1) has been revealed in various human solid tumors, the functions and potential mechanisms of Egr1 in the progression of salivary gland pleomorphic adenoma (SGPA) are not entirely understood. RESULTS: An elevated expression of Egr1 was observed both in the human salivary gland pleomorphic adenoma tissues and tumor-initiating cell (TIC) cells, when compared with control group. By loss-of-function assay, the proliferation and invasion capacities of TICs were inhibited, while the cell apoptosis was promoted, which were further evidenced by the protein expression analysis of several key apoptosis-related regulators. Furthermore, TICs with Mithramycin A (an Egr1 inhibitor) treatment achieved the same effects of endogenous Egr1 knockdown. CONCLUSIONS: All these data collectively suggest that Egr1 act as an oncogenic factor in salivary gland pleomorphic adenoma, which may be a potential target for the treatment of SGPA.

11.
Chemosphere ; 240: 124837, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31542575

RESUMO

Substantial changes have occurred in hydrological situation of the Three Gorges Reservoir (TGR) after the operation of the Three Gorges project, as have the heavy metals (HMs) pollution characteristics. In this study, concentrations of Cu, Zn, Pb, Cr, and Cd in surface water and sediments of the TGR were determined during the water impoundment period (December 2015) and water drawdown period (June 2016). The index of geoaccumulation, principal component analysis (PCA), and correlation analysis were used to analyze HMs pollution characteristics. Results showed that HMs concentrations in surface water were much lower than the quality standards for drinking water and surface water of China. The pollution levels of HMs in sediments were nonpolluted for Cr, nonpolluted to moderately polluted for Cu, Zn, Pb, and moderately polluted for Cd. In the fluctuating backflow zone, HMs concentrations in sediments during the water drawdown period were lower than those during the water impoundment period, which was attributed to that faster flow velocity during the water drawdown period resulted in less deposition of suspended solids and faster release of HMs pollutants from sediments to water. HMs concentrations of sediments at sites M14 and M17 showed similar periodic changes to those at the fluctuating backflow zone, which might be attributed to the density-stratified flow in the adjacent upstream tributaries (Meixi River and Qinggan River, respectively). Correlation analysis and PCA analysis results showed that for the sediments, Cr came from natural sources, while Cu, Zn, Pb, and Cd mainly came from anthropogenic sources.


Assuntos
Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Metais Pesados/química , China
12.
Talanta ; 206: 120200, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514845

RESUMO

Highly-sensitive and contamination-free droplet digital PCR (ddPCR) is an enabling technology and widely needed for accurate quantification of nucleic acid in clinical applications. In this paper, a novel droplet reader was developed by combining a "quasi" confocal laser-induced fluorescence (LIF) cytometry with a delicate microfluidic chip design. The droplets with a size of 90 µm was illuminated at an out-of-focus position by two aligned laser beams to generate maximum fluorescent signal. Additionally, the lateral offset position of the microfluidic chip should be precisely tuned so that the bandwidth of the FAM and VIC channels were configured at the matching sizes. Then, PMT gain voltages and pneumatic pressures were optimized for better droplet detection efficiencies. An aerosol adsorption experiment was performed to demonstrate that there was no aerosol contamination, and detected copy numbers of both mutants and wild types scaled linearly with the expected input copy numbers (r2>0.998) with a LoB of 0.0 copies and LoD of 3.0 copies. The results demonstrated that this droplet reader with the delicate chip is a convenient, highly-sensitive and contamination-free to detect fluorescence signals inside droplets after ddPCR, which is highly promising for broad applications of ddPCR in clinical diagnosis.


Assuntos
DNA/análise , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/métodos , Reação em Cadeia da Polimerase/métodos , Desenho de Equipamento , Receptores ErbB/genética , Antígeno HLA-B27/genética , Limite de Detecção , Técnicas Analíticas Microfluídicas/instrumentação , Mutação , Reação em Cadeia da Polimerase/instrumentação
13.
Cell Res ; 30(2): 133-145, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31853004

RESUMO

Multisystem manifestations in myotonic dystrophy type 1 (DM1) may be due to dosage reduction in multiple genes induced by aberrant expansion of CTG repeats in DMPK, including DMPK, its neighboring genes (SIX5 or DMWD) and downstream MBNL1. However, direct evidence is lacking. Here, we develop a new strategy to generate mice carrying multigene heterozygous mutations to mimic dosage reduction in one step by injection of haploid embryonic stem cells with mutant Dmpk, Six5 and Mbnl1 into oocytes. The triple heterozygous mutant mice exhibit adult-onset DM1 phenotypes. With the additional mutation in Dmwd, the quadruple heterozygous mutant mice recapitulate many major manifestations in congenital DM1. Moreover, muscle stem cells in both models display reduced stemness, providing a unique model for screening small molecules for treatment of DM1. Our results suggest that the complex symptoms of DM1 result from the reduced dosage of multiple genes.

14.
Environ Sci Pollut Res Int ; 27(7): 7071-7086, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31883081

RESUMO

The optimal allocation of sediment resources needs to balance three objectives including ecological, economic, and social benefits so as to realize sustainable development of sediment resources. This study aims to apply fuzzy programming and bargaining approaches to solve the problem of optimal allocation of sediment resources. Firstly, Pareto-optimal solutions of multi-objective optimization were introduced, and the multi-objective optimal allocation model of sediment resources and fuzzy programming model was constructed. Then, from the perspective of multiplayer cooperation, the optimal allocation model of sediment resources was transformed into a game model by using Nash bargaining, and Nash bargaining solution was obtained as the optimal equilibrium strategy. Finally, the influence of different disagreement utility points and bargaining weights on the results was discussed, and the results of Nash bargaining and fuzzy programming methods were compared and analyzed. Results corroborate that Nash bargaining can achieve the cooperative optimization of multiple objectives with competitive relationship and obtain satisfactory scheme. Disagreement utility points and bargaining weights have a certain impact on the optimization results. The solution of fuzzy programming is close to that of Nash bargaining, which provides different ideas for multi-objective optimization problem.

15.
Ann Hepatol ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31870745

RESUMO

INTRODUCTION AND OBJECTIVES: Hepatitis B virus (HBV) might be an etiological factor modulating fat distribution in steatotic livers. We aim to compare hepatic steatosis distribution patterns between NAFLD and FL&CHB patients with second-harmonic generation (SHG)/two-photon excited fluorescence (TPEF) method. PATIENTS AND METHODS: 42 patients with NAFLD, 46 with FL&CHB and 55 without steatosis were enrolled in the study. Overall and regional steatosis in liver sections were quantified by SHG/TPEF method. The accuracy of which was validated by pathologist evaluation and magnetic resonance spectroscopy (MRS). Difference in degree of overall and regional steatosis between NAFLD and FL&CHB groups was analyzed by Mann-Whitney U test. Multivariable linear regression analysis was used to model factors contributing to steatosis distribution. RESULTS: The hepatic steatosis measured by SHG/TPEF method was highly correlated with pathologist grading (r=0.83, p<0.001) and MRS measurement (r=0.82, p<0.001). The level of overall steatosis in FL&CHB group is significantly lower than that in NAFLD group (p<0.001). In NAFLD group, periportal region has significantly lower steatosis percentage than lobule region and overall region (p<0.001); while in FL&CHB group there is no difference among regions. The ratio of steatosis at periportal region to lobule region is significantly higher in FL&CHB group than that in NAFLD group (p<0.05). Multivariable linear regression analysis shows that HBV infection is the major contributing factor (ß=0.322, p<0.01). CONCLUSIONS: SHG/TPEF method is an accurate and objective method in hepatic steatosis quantification. By quantifying steatosis in different histological regions, we found steatosis distribution patterns are different between FL&CHB and NAFLD patients.

16.
J Microsc ; 276(3): 118-127, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31696930

RESUMO

White light interferometry (WLI) is an effective and widely-used technique for structured surface measurement. However, it requires multiframe interferograms with vertical scanning to realise large-scale measurement, which is time consuming and computationally intensive. This paper proposes a rapid surface measurement method to realise surface recovery with a single interferogram by white light interferometry. First, the feasibility to solve the wrapped phase of a single white-light interferogram by Hilbert transform is certified. Then, unwrapped phases against zero optical path difference position (OPD) are achieved by a zero optical path difference detection algorithm applied to unwrapping process, which provides efficient surface recovery. To ensure the accuracy of phase solution in the proposed method, the necessary number and width of the interference fringes in the interferogram are analysed and determined based on Hilbert transform and sampling analysis. Finally, measurement results of a standard step sample and a standard reticle template are presented, which prove the accuracy and efficiency of the proposed method. LAY DESCRIPTION: As an effective and widely-used technique for structured surface measurement, white light interferometry (WLI) has the major advantage to measure noncontinuous surfaces using the short coherence length of a wide bandwidth source. However, frequently vertical scanning is required to get series of white light interferograms at different axial positions for surface recovery by recovered algorithms. The vertical scanning process is complicated and time consuming. This paper proposes a fast and efficient method to realise rapid surface measurement using only a single-frame interferogram based on WLI. First, the feasibility of using only one single white light interferogram to solve wrapped phases by Hilbert transform (HT) is discussed. Next, unwrapping process and zero optical path difference(OPD) detection algorithms are combined to unwrap phases against zero OPD position, which makes the structured surface recovery much easier. After that, the feasible number and width of interference fringes are determined based on sampling analysis and HT to guarantee the reliability and accuracy of phase solution in the proposed method. Finally, the accuracy and efficiency of this method is verified by measurement experiments of a standard step sample and a standard reticle template.

17.
J Cancer ; 10(25): 6457-6465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772678

RESUMO

Gene methylation is an epigenetic alteration in hepatocellular carcinoma (HCC), and hepatitis B virus (HBV) plays a crucial role in carcinogenesis of HCC. However, the association between gene methylation and HBV infection in HCC remains unclear. In our study, we conducted a comprehensive meta-analysis to evaluate the association. A total of 1,148 studies were initially retrieved from some literature database. After a four-step filtration, we obtained 69 case-control studies in this meta-analysis. Our results showed six genes (p16, RASSF1A, GSTP1, APC, p15 and SFRP1) in HBV-positive carcinoma tissues, one gene (GSTP1) in HBV-positive adjacent tissues and two gene (p16 and APC) in HBV-positive carcinoma serums, which were significantly hypermethylated. Subgroup meta-analysis by geographical populations revealed that GSTP1 methylation was significantly higher in HBV-positive carcinoma tissues in China and Japan. In addition, p16 and RASSF1A methylation was significantly higher in China but not in Japan. Our study indicated that HBV infection could induce DNA methylation in HCC and DNA methylation could lead to the development of HBV-related HCC.

18.
Obesity (Silver Spring) ; 27(12): 2055-2066, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31657148

RESUMO

OBJECTIVE: Bile acids (BAs) are important molecules in the progression of nonalcoholic fatty liver disease. This study aimed to investigate BA profile alterations in Chinese nonalcoholic steatohepatitis (NASH) patients. METHODS: BA profiles in serum and liver tissues were determined by ultraperformance liquid chromatography coupled to tandem mass spectrometry in patients from two different clinical centers. RESULTS: A total of 134 participants were enrolled in this study to serve as the training (n = 87) and validation (n = 47) cohorts. The ratio of circulating conjugated chenodeoxycholic acids to muricholic acids (P = 0.001) was elevated from healthy controls to non-NASH individuals to NASH individuals in a stepwise manner in the training cohort and was positively associated with the histological severity of NASH: steatosis (R2 = 0.12), lobular inflammation (R2 = 0.12), ballooning (R2 = 0.11), and fibrosis stage (R2 = 0.18). The ratio was elevated in the validation cohort of NASH patients (P < 0.001), and it was able to predict NASH (area under the receiver operating characteristic curve: 75%) and significant fibrosis (area under the receiver operating characteristic curve: 71%) in these two cohorts. Moreover, this elevated ratio and impaired farnesoid X receptor signaling were found in the NASH liver. CONCLUSIONS: Altered BA profile in NASH is closely associated with the severity of liver lesions, and it has the potential for predicting NASH development.

19.
Int J Endocrinol ; 2019: 3206587, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485221

RESUMO

Objectives: The aim of this study was to investigate the effects of compound C on an in vivo mouse model of high-fat diet- (HFD-) induced obesity and hepatosteatosis. Methods: C57BL/6 mice were fed with a standard diet (n = 5) for 16 weeks and then injected saline once a day for 4 weeks as the normal chow group. Mice (n = 10) were fed with HFD for 16 weeks to induce obesity and hepatosteatosis and then divided into two groups: HFD + vehicle group injected with the vehicle solution (saline) and HFD + compound C group injected with compound C in saline (5 mg/kg i.p., once a day) for 4 weeks. Liver histology was observed. The expression levels of genes related to lipid metabolism and proinflammation in liver tissue were examined. NLRP3 inflammasome expression in liver tissue was detected by the western blot assay. HepG2 cells were pretreated with compound C and/or AICAR for 1 h and then treated with palmitic acid (PA) for 3 h. The cells were collected, and mRNA levels were determined. Results: There was a significant reduction in body-weight gain and daily food intake in the HFD + compound C group compared with the HFD + vehicle group (p < 0.05). The glucose tolerance test (GTT) and insulin tolerance test (ITT) showed that compound C alleviated insulin resistance. Histology analysis showed a significant reduction of hepatic steatosis by compound C. Compound C also significantly decreased fatty acid synthesis genes, while increased fatty acid oxidation genes. Furthermore, compound C significantly reduced the expression of proinflammatory markers and NLRP3 inflammasome (p < 0.05). Compound C enhanced mRNA levels of SOD1, SOD2, catalase, GPx1, and GPx4 and reduced the p-AMPK/AMPK ratio, which were stimulated by palmitic acid (PA). The effect was enhanced by AICAR. Conclusion: Our data suggest that compound C is a potent NAFLD suppressor and an attractive therapeutic target for hepatic steatosis and related metabolic disorders.

20.
Opt Express ; 27(16): 22737-22752, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510560

RESUMO

Characterization of the displacement response is critical for accurate chromatic confocal measurement. Current characterization methods usually provide a linear or polynomial relationship between the extracted peak wavelengths of the spectral signal and displacement. However, these methods are susceptible to errors in the peak extraction algorithms and errors in the selected model. In this paper, we propose a hybrid radial basis function network method to characterise the displacement response. With this method, the peak wavelength of the spectral signal is firstly extracted with a state-of-art peak extraction algorithm, following which, a higher-accuracy chromatic dispersion model is applied to determine the displacement-wavelength relationship. Lastly, a radial basis function network is optimized to provide a mapping between the spectral signals and the residual fitting errors of the chromatic dispersion model. Using experimental tests, we show that the hybrid radial basis function network method significantly improves the measurement accuracy, when compared to the existing characterizing methods.

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