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1.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5278-5284, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38114117

RESUMO

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 µmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 µmol·L~(-1)), low-concentration(10 µmol·L~(-1)) saikosaponin D, and high-concentration(16 µmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.


Assuntos
Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Caspase 3 , Proteína X Associada a bcl-2 , Proteína Beclina-1/farmacologia , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/genética , Apoptose , Neoplasias Pancreáticas/tratamento farmacológico , Caspases , Autofagia
2.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(5): 737-744, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31631621

RESUMO

This study aims to explore the effect of aortic sinus diameter on aortic valve opening and closing performance in the case of no obvious disease of aortic valve and annulus and continuous dilation of aortic root. A total of 25 three-dimensional aortic root models with different aortic sinus and root diameters were constructed according to the size of clinical surgical guidance. The valve sinus diameter DS is set to 32, 36, 40, 44 and 48 mm, respectively, and the aortic root diameter DA is set to 26, 27, 28, 29 and 30 mm, respectively. Through the structural mechanics calculation with the finite element software, the maximum stress, valve orifice area, contact force and other parameters of the model are analyzed to evaluate the valve opening and closing performance under the dilated state. The study found that aortic valve stenosis occurs when the DS = 32 mm, DA = 26, 27 mm and DS = 36 mm, DA = 26 mm. Aortic regurgitation occurs when the DS = 32, 36 and 40 mm, DA = 30 mm and DS = 44, 48 mm, DA = 29, 30 mm. The other 15 models had normal valve movement. The results showed that the size of the aortic sinus affected the opening and closing performance of the aortic valve. The smaller sinus diameter adapted with the larger root diameter and the larger sinus diameter adapted with the smaller root diameter. When the sinus diameter is 40 mm, the mechanical performance of the valve are good and it can well adapt with the relatively large range of aortic root dilation.


Assuntos
Aorta/anatomia & histologia , Insuficiência da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/fisiopatologia , Valva Aórtica/fisiologia , Humanos
3.
Nanotechnology ; 29(44): 445701, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30113909

RESUMO

In this study, nanocrystalline-assembled mesoporous Cu2O microspheres (MCMs) with enhanced visible-light driven photocatalytic activity were synthesized by a facile one-step hydrothermal method. MCMs exhibit excellent visible-light driven photocatalytic activity with 85% removal of methyl orange (MO) (60% removal of total organic carbon (TOC)) in 40 min. The excellent photocatalytic performance is dependent on the specific morphology and excellent visible-light absorption ability. Interestingly, MCMs can efficiently remove MO with or without light. The amount and categories of active species were determined by electron paramagnetic resonance and photoluminance (PL). Reactive oxygen species (ROS) (mainly ·[Formula: see text] and H2O2) and Cu (I) radicals are important in fading and further mineralization of MO. With the assistance of gas chromatography-mass spectrometer , TOC and x-ray photoelectron spectroscopy, the degradation pathways in light and dark conditions were analyzed. It has been proven that MO could be efficiently mineralized by ROS generated in light, while reaction in dark condition was more likely to be an efficient fading process.

4.
Food Chem ; 438: 138000, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38000154

RESUMO

ß-Cyclodextrin (ß-CD) Pickering emulsion and cinnamaldehyde/ß-cyclodextrin (CIN/ß-CD) Pickering emulsion were prepared and the influences of oxidation and digestion were investigated. CIN/ß-CD composite was better dispersed at the oil-water interface than ß-CD. Hydrophobic group of CIN anchored in the oil phase and Hydrophilic hydroxyl group of ß-CD extended into the aqueous phase, which allowed CIN/ß-CD composite to be oriented at the oil-water interface and formed a more stable oil-water interface layer. ß-CD Pickering emulsion was more susceptible to oxidative deterioration than CIN/ß-CD Pickering emulsion, its malondialdehyde (MDA) value was as high as 509.41 ± 9.37 nmol/L. Digestion experiment indicated that CIN/ß-CD Pickering emulsion was released inner oil phase in the small intestine and free fatty acid (FFA) release rate was 44.32 ± 1.08%. Pharmacokinetic parameters manifested that α-tocopherol peak concentration (Cmax) was 64.32 ± 6.45 mg/L and the peak time (Tmax) appeared at 5 h after administration of CIN/ß-CD Pickering emulsion.


Assuntos
Antioxidantes , beta-Ciclodextrinas , Emulsões/química , Antioxidantes/química , alfa-Tocoferol , beta-Ciclodextrinas/química , Água/química , Tamanho da Partícula
5.
Oncol Lett ; 25(5): 205, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37123022

RESUMO

The objective of the present study was to investigate the role of postoperative radiotherapy (PORT) after radical resection of stage IIIA-N2 non-small cell lung cancer (NSCLC). Subgroups of patients who benefited from PORT were evaluated. A retrospective review of 288 consecutive patients with resected pIIIA-N2 NSCLC at Beijing Chest Hospital (Beijing, China) was performed. Of these patients, 61 received PORT. The 288 patients were divided into PORT and non-PORT groups according to the treatment received. The baseline characteristics of the two patient groups were balanced using propensity score-matching (PSM; 1:1 matching). In total, 60 patients in the PORT group and 60 patients in the non-PORT group were matched. After PSM, the median survival time of the matched patients was 53 months. The 1-, 3- and 5-year overall survival (OS) rates of the PORT patient group were 95.0, 63.2 and 48.2%, respectively, while those of the non-PORT group were 86.7, 58.3 and 34.5%, respectively, and there was no significant difference between the two groups (P=0.056). The 5-year local recurrence-free survival (LRFS) rate in the PORT group was significantly improved (P=0.001). The effects of PORT on OS and LRFS rates were analysed in patients with different clinicopathological features. For subgroups with multiple N2 stations, N2 positive lymph nodes ≥4 and squamous cell carcinoma, PORT significantly increased the OS and LRFS rates (P<0.05). In conclusion, there was no statistically significant improvement in the 5-year OS rate with PORT overall, but there may be subgroups, such as patients with multiple N2 stations, N2 positive nodes ≥4 and squamous cell carcinoma histology, that could be explored as potentially benefitting from improved 5-year OS and LRFS rates with PORT.

6.
Artigo em Inglês | MEDLINE | ID: mdl-37716344

RESUMO

In this work, an imidazolium-based poly (ionic liquid) (poly(1-octyl-3-vinyl- imidazolium naphthalene sulfonate)) functionalized silica (poly(C8VIm+NapSO3-) @SiO2) was successfully prepared for the determination of parabens in food samples. The prepared poly(C8VIm+NapSO3-)@SiO2 was characterized by Fourier transform infrared spectrometry (FT-IR), X-ray photoelectron spectrogram (XPS) and Scanning electron microscopy (SEM). The simulation calculation results indicated that the suitable binding energies were between the polymeric ionic liquids and parabens, and the main interactions for extraction were hydrogen bonding, electrostatic and π-π stacking interactions. In addition, compared with commercial extraction materials, the prepared poly(C8VIm+NapSO3-)@SiO2 sorbent showed comparable or even better extraction performance towards parabens. The effective parameters were optimized by a combination of the univariate method and Box-Behnken design (BBD). Under the optimum conditions, coupled with high performance liquid chromatography (HPLC), wide linear ranges (1.0-800 µg L-1), good linearity (R2 ≥ 0.9997) and low limits of detection (0.1 µg L-1) were obtained. In addition, the intra-day and inter-day relative standard deviations (RSDs) were all lower than 6.3%. Moreover, the proposed method was successfully used for the determination of parabens in food samples and satisfactory recoveries in the range of 76.9-97.4% were obtained. The results indicated that the proposed method had good sensitivity, accuracy and precision for the detection of parabens in food samples.


Assuntos
Líquidos Iônicos , Líquidos Iônicos/química , Dióxido de Silício/química , Parabenos/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Adsorção , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção
7.
Phytomedicine ; 120: 155068, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37690228

RESUMO

BACKGROUND: Lycium barbarum L. is a typical Chinese herbal and edible plant and are now consumed globally. Low molecular weight L. barbarum L. oligosaccharides (LBO) exhibit better antioxidant activity and gastrointestinal digestibility in vitro than high molecular weight polysaccharides. However, the LBO on the treatment of liver disease is not studied. PURPOSE: Modification of the gut microbial ecosystem by LBO is a promising treatment for liver fibrosis. STUDY DESIGN AND METHODS: Herein, LBO were prepared and characterized. CCl4-treated mice were orally gavaged with LBO and the effects on hepatic fibrosis and mitochondrial abnormalities were evaluated according to relevant indicators (gut microbiota, faecal metabolites, and physiological and biochemical indices). RESULTS: The results revealed that LBO, a potential prebiotic source, is a pyranose cyclic oligosaccharide possessing α-glycosidic and ß-glycosidic bonds. Moreover, LBO supplementation restored the configuration of the bacterial community, enhanced the proliferation of beneficial species in the gastrointestinal tract (e.g., Bacillus, Tyzzerella, Fournierella and Coriobacteriaceae UCG-002), improved microbial metabolic alterations (i.e., carbohydrate metabolism, vitamin metabolism and entero-hepatic circulation), and increased antioxidants, including doxepin, in mice. Finally, LBO administration reduced serum inflammatory cytokine and hepatic hydroxyproline levels, improved intestinal and hepatic mitochondrial functions, and ameliorated mouse liver fibrosis. CONCLUSION: These findings indicate that LBO can be utilized as a prebiotic and has a remarkable ability to mitigate liver fibrosis.


Assuntos
Lycium , Animais , Camundongos , Antioxidantes/farmacologia , Cirrose Hepática/tratamento farmacológico , Oligossacarídeos , Microbioma Gastrointestinal
8.
Foods ; 12(19)2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37835211

RESUMO

Herein, we applied the Illumina MiSeq pyrosequencing platform to amplify the V3-V4 hypervariable regions of the 16 S rRNA gene of the gut microbiota (GM) and a gas chromatograph-mass spectrometer to detect the metabolites after supplementation with pumpkin oligosaccharides (POSs) to determine the metabolic markers and mechanisms in rats with type 2 diabetes (T2D). The POSs alleviated glucolipid metabolism by decreasing the serum low-density lipoprotein (LDL), total cholesterol (TC), and glucose levels. These responses were supported by a shift in the gut microbiota, especially in the butyric-acid-producing communities. Meanwhile, elevated total short-chain fatty acid (SCFA), isovaleric acid, and butyric acid levels were observed after supplementation with POSs. Additionally, this work demonstrated that supplementation with POSs could reduce TNF-α and IL-6 secretion via the FFA2-Akt/PI3K pathway in the pancreas. These results suggested that POSs alleviated T2D by changing the SCFA-producing gut microbiota and SCFA receptor pathways.

9.
Bioinformatics ; 27(21): 2936-43, 2011 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-21903628

RESUMO

MOTIVATION: Many new methods have recently been proposed for detecting epistatic interactions in GWAS data. There is, however, no in-depth independent comparison of these methods yet. RESULTS: Five recent methods-TEAM, BOOST, SNPHarvester, SNPRuler and Screen and Clean (SC)-are evaluated here in terms of power, type-1 error rate, scalability and completeness. In terms of power, TEAM performs best on data with main effect and BOOST performs best on data without main effect. In terms of type-1 error rate, TEAM and BOOST have higher type-1 error rates than SNPRuler and SNPHarvester. SC does not control type-1 error rate well. In terms of scalability, we tested the five methods using a dataset with 100 000 SNPs on a 64 bit Ubuntu system, with Intel (R) Xeon(R) CPU 2.66 GHz, 16 GB memory. TEAM takes ~36 days to finish and SNPRuler reports heap allocation problems. BOOST scales up to 100 000 SNPs and the cost is much lower than that of TEAM. SC and SNPHarvester are the most scalable. In terms of completeness, we study how frequently the pruning techniques employed by these methods incorrectly prune away the most significant epistatic interactions. We find that, on average, 20% of datasets without main effect and 60% of datasets with main effect are pruned incorrectly by BOOST, SNPRuler and SNPHarvester. AVAILABILITY: The software for the five methods tested are available from the URLs below. TEAM: http://csbio.unc.edu/epistasis/download.php BOOST: http://ihome.ust.hk/~eeyang/papers.html. SNPHarvester: http://bioinformatics.ust.hk/SNPHarvester.html. SNPRuler: http://bioinformatics.ust.hk/SNPRuler.zip. Screen and Clean: http://wpicr.wpic.pitt.edu/WPICCompGen/. CONTACT: wangyue@nus.edu.sg.


Assuntos
Epistasia Genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Software
10.
Biomed Res Int ; 2022: 5489553, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467888

RESUMO

Saikosaponin D (SSD), a saponin derivative, is extracted from Bupleurum falcatum. It exhibits an inhibitory effect on a number of tumor cells and is relatively safe when used at therapeutic doses. However, its effects on glioblastoma multiforme (GBM) have not been fully explored. This study is aimed at investigating the cytotoxic effects of SSD in GBM cell lines. SSD induces apoptosis and autophagy by activating endoplasmic reticulum (ER) stress in GBM cells. GBM cell proliferation activity and morphology were observed using the Cell Counting Kit-8 assay and hematoxylin and eosin staining. Hoechst 33258 fluorescence staining and flow cytometry were performed to assess apoptosis. Western blotting and immunocytochemical staining were used to detect protein expression and distribution. SSD significantly inhibited the proliferation of RG-2, U87-MG, and U251 cells in a dose-dependent manner, and the proportion of apoptotic cells increased significantly. Additionally, the expressions of ER-, apoptosis-, and autophagy-related proteins were significantly upregulated and distributed in the cytoplasm and nucleus. Therefore, SSD may be considered a novel treatment option for GBM. This study demonstrated the anti-GBM effect of SSD from the perspectives of cell apoptosis and autophagy.


Assuntos
Glioblastoma , Saponinas , Humanos , Estresse do Retículo Endoplasmático , Glioblastoma/tratamento farmacológico , Saponinas/farmacologia , Autofagia , Apoptose
11.
Food Sci Nutr ; 10(6): 2101-2110, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35702278

RESUMO

Germination and ultrasonic-assisted extraction (UAE) are economical and effective methods to enhance bioactive compounds in plant seeds. We optimized the germination parameters and UAE parameters by using response surface methodology to maximize the recovery of γ-aminobutyric acid (GABA) in pumpkin seeds. The optimal germination conditions were as follows: soaking the seeds at 28°C for 6 h with 0.2% CaCl2, 3.8 mg/ml monosodium glutamate, and 4.0 mg/ml vitamin B6, then germination at 30°C for 61.6 h. The optimal conditions for UAE were as follows: 1:75 (w/v) material-to-solvent ratio, 220 W ultrasonic power, and ultrasonic treatment at 50°C for 14.4 min, which afforded an extraction yield of 2679 ± 10 mg/100 g. Moreover, the GABA-enhanced extract showed the potential of hypolipidemic effect in type 2 diabetes rats. These results confirmed that a combination of germination and UAE increased the GABA yield from pumpkin seeds and provided a basis for GABA-enhanced production to improve lifestyle-associated diseases.

12.
Nutrients ; 14(22)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36432405

RESUMO

Subclinical mastitis (SCM) is an inflammatory state of the lactating mammary gland, which is asymptomatic and may have negative consequences for child growth. The objectives of this study were to: (1) test the association between the dietary inflammatory index (DII®) and SCM and (2) assess the differences in nutrient intakes between women without SCM and those with SCM. One hundred and seventy-seven women with available data on human milk (HM) sodium potassium ratio (Na:K) and dietary intake data were included for analysis. Multivariable logistic regression was used to examine the association between nutrient intake and the DII score in relation to SCM. Women without SCM had a lower median DII score (0.60) than women with moderate (1.12) or severe (1.74) SCM (p < 0.01). A one-unit increase in DII was associated with about 41% increased odds of having SCM, adjusting for country and mode of delivery, p = 0.001. Women with SCM had lower mean intakes of several anti-inflammatory nutrients. We show for the first time exploratory evidence that SCM may be associated with a pro-inflammatory diet and women with SCM have lower intakes of several antioxidant and anti-inflammatory nutrients.


Assuntos
Lactação , Mastite , Feminino , Humanos , Dieta , Mastite/complicações , Leite Humano/química , Sódio/análise
13.
Proteome Sci ; 9 Suppl 1: S15, 2011 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-22165860

RESUMO

BACKGROUND: Protein complexes are important for understanding principles of cellular organization and functions. With the availability of large amounts of high-throughput protein-protein interactions (PPI), many algorithms have been proposed to discover protein complexes from PPI networks. However, existing algorithms generally do not take into consideration the fact that not all the interactions in a PPI network take place at the same time. As a result, predicted complexes often contain many spuriously included proteins, precluding them from matching true complexes. RESULTS: We propose two methods to tackle this problem: (1) The localization GO term decomposition method: We utilize cellular component Gene Ontology (GO) terms to decompose PPI networks into several smaller networks such that the proteins in each decomposed network are annotated with the same cellular component GO term. (2) The hub removal method: This method is based on the observation that hub proteins are more likely to fuse clusters that correspond to different complexes. To avoid this, we remove hub proteins from PPI networks, and then apply a complex discovery algorithm on the remaining PPI network. The removed hub proteins are added back to the generated clusters afterwards. We tested the two methods on the yeast PPI network downloaded from BioGRID. Our results show that these methods can improve the performance of several complex discovery algorithms significantly. Further improvement in performance is achieved when we apply them in tandem. CONCLUSIONS: The performance of complex discovery algorithms is hindered by the fact that not all the interactions in a PPI network take place at the same time. We tackle this problem by using localization GO terms or hubs to decompose a PPI network before complex discovery, which achieves considerable improvement.

14.
Food Funct ; 12(19): 9273-9285, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606538

RESUMO

This study aimed to explore the protection mechanism of a debranched corn starch/konjac glucomannan (DCSK) composite against type 2 diabetes (T2D) related to dyslipidemia and gut microbiota in mice fed on a high-fat diet (HFD). The results showed that the consumption of DCSK led to a significant improvement in the biochemical parameters and physiological indices associated with T2D in the HFD group, including the decrease in blood glucose, triglyceride, total cholesterol, and high-density lipoprotein cholesterol levels, as well as the suppression of the oxidative stress of the liver and kidneys. Furthermore, the health of the intestinal microbiota in the HFD-fed mice was altered dramatically after DCSK consumption. Metabolomics revealed 13 differential metabolites strongly linked to DCSK intervention, and DCSK supplementation regulated amino acid metabolism, nucleotide metabolism, and lipid metabolism. These findings demonstrated that DCSK has an outstanding ability to improve hyperglycemia, hyperlipidemia, and gut microbiota associated with T2D.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Suplementos Nutricionais , Dislipidemias/prevenção & controle , Microbioma Gastrointestinal , Mananas , Amido , Animais , Glicemia/metabolismo , Peso Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/complicações , Rim/patologia , Fígado/patologia , Masculino , Redes e Vias Metabólicas , Camundongos , Camundongos Endogâmicos C57BL
15.
Front Physiol ; 12: 697502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526908

RESUMO

Patients with aortic valve disease can suffer from valve insufficiency after valve repair surgery due to aortic root dilatation. The paper investigates the effect of valve height (Hv) on the aortic valve opening and closing in order to select the appropriate range of Hv for smoother blood flow through the aortic valve and valve closure completely in the case of continuous aortic root dilatation. A total of 20 parameterized three-dimensional models of the aortic root were constructed following clinical surgical guidance. Aortic annulus diameter (DAA) was separately set to 26, 27, 28, 29, and 30 mm to simulate aortic root dilatation. HV value was separately set to 13.5, 14, 14.5, and 15 mm to simulate aortic valve alterations in surgery. Time-varying pressure loads were applied to the valve, vessel wall of the ascending aorta, and left ventricle. Then, finite element analysis software was employed to simulate the movement and mechanics of the aortic root. The feasible design range of the valve size was evaluated using maximum stress, geometric orifice area (GOA), and leaflet contact force. The results show that the valve was incompletely closed when HV was 13.5 mm and DAA was 29 or 30 mm. The GOA of the valve was small when HV was 15 mm and DAA was 26 or 27 mm. The corresponding values of the other models were within the normal range. Compared with the model with an HV of 14 mm, the model with an HV of 14.5 mm could effectively reduce maximum stress and had relatively larger GOA and less change in contact force. As a result, valve height affects the performance of aortic valve opening and closing. Smaller HV is adapted to smaller DAA and vice versa. When HV is 14.5 mm, the valve is well adapted to the dilatation of the aortic root to enhance repair durability. Therefore, more attention should be paid to HV in surgical planning.

16.
BMC Bioinformatics ; 11: 66, 2010 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-20113476

RESUMO

BACKGROUND: Human genome contains millions of common single nucleotide polymorphisms (SNPs) and these SNPs play an important role in understanding the association between genetic variations and human diseases. Many SNPs show correlated genotypes, or linkage disequilibrium (LD), thus it is not necessary to genotype all SNPs for association study. Many algorithms have been developed to find a small subset of SNPs called tag SNPs that are sufficient to infer all the other SNPs. Algorithms based on the r2 LD statistic have gained popularity because r2 is directly related to statistical power to detect disease associations. Most of existing r2 based algorithms use pairwise LD. Recent studies show that multi-marker LD can help further reduce the number of tag SNPs. However, existing tag SNP selection algorithms based on multi-marker LD are both time-consuming and memory-consuming. They cannot work on chromosomes containing more than 100 k SNPs using length-3 tagging rules. RESULTS: We propose an efficient algorithm called FastTagger to calculate multi-marker tagging rules and select tag SNPs based on multi-marker LD. FastTagger uses several techniques to reduce running time and memory consumption. Our experiment results show that FastTagger is several times faster than existing multi-marker based tag SNP selection algorithms, and it consumes much less memory at the same time. As a result, FastTagger can work on chromosomes containing more than 100 k SNPs using length-3 tagging rules.FastTagger also produces smaller sets of tag SNPs than existing multi-marker based algorithms, and the reduction ratio ranges from 3%-9% when length-3 tagging rules are used. The generated tagging rules can also be used for genotype imputation. We studied the prediction accuracy of individual rules, and the average accuracy is above 96% when r2 >/= 0.9. CONCLUSIONS: Generating multi-marker tagging rules is a computation intensive task, and it is the bottleneck of existing multi-marker based tag SNP selection methods. FastTagger is a practical and scalable algorithm to solve this problem.


Assuntos
Algoritmos , Mapeamento Cromossômico/métodos , Análise Mutacional de DNA/métodos , Marcadores Genéticos/genética , Desequilíbrio de Ligação/genética , Polimorfismo de Nucleotídeo Único/genética , Software
17.
Bioinformatics ; 25(15): 1891-7, 2009 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-19435747

RESUMO

MOTIVATION: Protein complexes are important for understanding principles of cellular organization and function. High-throughput experimental techniques have produced a large amount of protein interactions, which makes it possible to predict protein complexes from protein-protein interaction (PPI) networks. However, protein interaction data produced by high-throughput experiments are often associated with high false positive and false negative rates, which makes it difficult to predict complexes accurately. RESULTS: We use an iterative scoring method to assign weight to protein pairs, and the weight of a protein pair indicates the reliability of the interaction between the two proteins. We develop an algorithm called CMC (clustering-based on maximal cliques) to discover complexes from the weighted PPI network. CMC first generates all the maximal cliques from the PPI networks, and then removes or merges highly overlapped clusters based on their interconnectivity. We studied the performance of CMC and the impact of our iterative scoring method on CMC. Our results show that: (i) the iterative scoring method can improve the performance of CMC considerably; (ii) the iterative scoring method can effectively reduce the impact of random noise on the performance of CMC; (iii) the iterative scoring method can also improve the performance of other protein complex prediction methods and reduce the impact of random noise on their performance; and (iv) CMC is an effective approach to protein complex prediction from protein interaction network. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Biologia Computacional/métodos , Mapeamento de Interação de Proteínas/métodos , Proteínas/química , Sítios de Ligação , Análise por Conglomerados
18.
Carbohydr Polym ; 229: 115534, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826396

RESUMO

As a new platform of systems biology, metabolomics provides a powerful approach to discover therapeutic biomarkers and mechanism of metabolic disease. Type 2 diabetes mellitus (T2DM) is a global metabolic disease, thus, a urinary metabolomics profiling was analyzed to study the anti-diabetic effects and mechanism of stachyose (ST) on high-fat diet- and low dose streptozotocinc-induced T2DM rats. The results showed that ST treatment regulated the level of insulin, low-density lipoprotein cholesterol, and triglycerides, which demonstrates improvement in T2DM on ST treatment. Urinary samples from the ST and T2DM group were enrolled in metabolomics study, 21 differential metabolites were identified from urinary metabolomics analysis, indicating that the ST treatment partly exerted the anti-diabetes activity by regulating energy metabolism, gut microbiota changes and inflammation. A metabolomics strategy is both suitable and reliable for exploring the anti-diabetes effects and understanding the mechanisms of ST treatment against T2DM.


Assuntos
Biomarcadores/urina , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metabolômica , Oligossacarídeos/uso terapêutico , Animais , LDL-Colesterol/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Análise Discriminante , Metabolismo Energético/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Histamina/urina , Hipoglicemiantes/farmacologia , Insulina/sangue , Análise dos Mínimos Quadrados , Masculino , Oligossacarídeos/farmacologia , Análise de Componente Principal , Ratos , Ratos Wistar , Estreptozocina/toxicidade , Triglicerídeos/sangue
19.
Carbohydr Polym ; 235: 115904, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122473

RESUMO

In vitro digestive conditions were simulated to investigate the digestibility of polysaccharides prepared from squash (SPS). A small amount of free glucose monosaccharide was released after salivary and intestinal digestion due to the breakdown of α-(1 → 4)-glucose linkages and may form SPS or a starch impurity. At the same time, there was no obvious change in molecular weight distribution and reducing sugar content throughout this digestion period, demonstrating that the main structure of SPS was relatively stable under the simulated digestive conditions. Thus, most SPS can be transported intact to the large intestine. In addition, SPS alleviated type 2 diabetes (T2D) in rats. Moreover, the content of short-chain fatty acids (SCFAs) in the colon significantly increased after treatment with SPS. The present research provides insight into the non-digestibility of SPS, and suggests its utility to alleviate T2D by promoting the production of SCFA in the colon.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos Voláteis/biossíntese , Polissacarídeos/metabolismo , Animais , Colo/química , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Ácidos Graxos Voláteis/análise , Intestinos/química , Masculino , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Ratos , Ratos Wistar , Saliva/química , Saliva/metabolismo , Estômago/química , Estreptozocina/administração & dosagem
20.
Radiol Oncol ; 55(1): 66-76, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33885242

RESUMO

BACKGROUND: The beneficial effect of postoperative radiotherapy (PORT) on completely resected pathological IIIA-N2 (pIIIA-N2) non-small cell lung cancer (NSCLC) has been a subject of interest with controversy. The aim of the study was to distinguish the clinical efficacy of PORT on lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC) among pIIIA-N2 NSCLC. PATIENTS AND METHODS: Between October 2010 and September 2016, 288 consecutive patients with completely resected pIIIA-N2 NSCLC at Beijing Chest Hospital were retrospectively analyzed, which consisted of 194 cases of LADC and 85 cases of LSCC. There were 42 (21.6%) patients treated with PORT in LADC cases and 19 (22.3%) patients treated with PORT in LSCC cases. The 5-year overall survival (OS), loco-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method. The prognostic factors were determined using Cox's regression model. RESULTS: Among 194 cases of LADC, the 1-, 3-, and 5-year OS in the PORT group were 95.2%, 61.9% and 40.0%, respectively, while in the non-PORT group were 90.1%, 63.3% and 45.0% (p = 0.948). The use of postoperative chemotherapy (POCT) and smoking index ≥ 400 were both prognostic factors of 5-year rates of OS, LRFS and DMFS. On the other hand, among 85 cases of LSCC, the 1-, 3-, and 5-year OS in the PORT group were 94.7%, 63.2% and 63.2%, respectively, whereas in the non-PORT group were 86.4%, 48.5% and 37.1% (p = 0.026). In this group, only the use of PORT was a favorable prognostic factor for 5-year OS, LRFS and DMFS. CONCLUSIONS: Due to clinicopathological differences among completely resected pIIIA-N2 NSCLC, PORT may not be suitable to all patients. Our study distinguishes pIIIA-N2 LSCC from LADC by their positive responses to PORT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Escamosas/radioterapia , Neoplasias Pulmonares/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
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