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1.
J Cell Mol Med ; 24(2): 1541-1552, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793207

RESUMO

Both PNPLA3 I148M and hepatic inflammation are associated with nonalcoholic fatty liver disease (NAFLD) progression. This study aimed to elucidate whether PNPLA3 I148M is involved in NF-kB-related inflammation regulation in NAFLD. HepG2 cells homozygous for the PNPLA3 I148M mutation were used. The human PNPLA3 promoter sequence was screened for NF-kB binding sites using the MATCH and PATCH tools. NF-kB-mediated transcriptional regulation of the PNPLA3 gene was assessed by luciferase reporter assay, EMSA and ChIP-qPCR. Wild-type (I148I) and mutant (M148M) PNPLA3 were overexpressed using stable lentivirus-mediated transfection. The pCMV vector and siRNA were transiently transfected into cells to direct NF-kB overexpression and PNPLA3 silencing, respectively. A putative NF-kB binding site in the human PNPLA3 promoter was shown to be necessary for basal and NF-kB-driven transcriptional activation of PNPLA3 and protein/DNA complex formation. Supershift analysis demonstrated a protein/DNA complex specifically containing the NF-kB p65 and p50 subunits. ChIP-qPCR confirmed the endogenous binding of NF-kB to the human PNPLA3 promoter in response to NF-kB overexpression and palmitic acid (PA) challenge. The silencing of PNPLA3 blocked the overexpression of NF-kB or PA-induced TNF-α up-regulation. Moreover, mutant PNPLA3 overexpression prevented NF-kB inhibitor-induced down-regulation of TNF-α expression in PA-treated HepG2 cells. Finally, the overexpression of mutant but not wild-type PNPLA3 increased TNF-α expression and activated the ER stress-mediated and NF-kB-independent inflammatory IRE-1α/JNK/c-Jun pathway. Human PNPLA3 was shown to be a target of NF-kB, and PNPLA3 I148M mediated the regulatory effect of NF-kB on inflammation in PA-treated HepG2 cells, most likely via the IRE-1α/JNK/c-Jun ER stress pathway.

2.
Diabetes Care ; 42(12): 2334-2337, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31548243

RESUMO

OBJECTIVE: To determine whether visit-to-visit fasting glucose (VVFG) variability in young adulthood is associated with midlife hippocampal integrity and volume. RESEARCH DESIGN AND METHODS: Multivariable-adjusted linear regression models were used to estimate the association between VVFG variability and brain MRI variables in 543 CARDIA study participants. VVFG variability was defined by the SD of FG (SDFG), the coefficient of variation of the mean FG (CVFG), and the average real variability (ARVFG) over 25 years of follow-up. Hippocampal integrity fractional anisotropy (FA) and tissue volume standardized to intracranial volume were measured by 3T MRI at year 25. RESULTS: After multivariable adjustment, higher FG variability (1-SD increase) was associated with lower hippocampal FA (SDFG -0.015 [95% CI -0.026, -0.004]; CVFG -0.009 [95% CI -0.018, -0.001]; ARVFG -0.011 [95% CI -0.019, -0.002]) and lower hippocampal volume (SDFG -0.012 [95% CI -0.023, -0.001]). CONCLUSIONS: Higher VVFG variability in young adulthood is associated with lower midlife hippocampal integrity and volume, suggesting its value in predicting risk for hippocampal structural damage.

3.
J Nutr Biochem ; 72: 108212, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473513

RESUMO

Migration of vascular smooth muscle cell (VSMC) plays a critical role in the pathophysiology of hypertension and several other vascular diseases. Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a bioactive constituent from Curcuma longa, is commonly used as a spice, food additive or dietary pigment. It has several health benefits including antioxidant, anti-inflammatory and anticancer properties. This study examined the roles of curcumin in VSMC migration in hypertension and underlying mechanism. VSMC was isolated and prepared from thoracic aorta of Wistar-Kyoto rats and spontaneously hypertensive rats (SHR). VSMC migration was evaluated with Boyden chamber assay and wound-healing assay. Curcumin attenuated VSMC migration, inhibited nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) expression and reduced interleukin (IL)-1ß concentration in VSMC of SHR, which were similar to the effects of NLRP3 knockdown on IL-1ß concentration and VSMC migration. Curcumin inhibited NFκB activation in VSMC of SHR, which was similar to the effects of NFκB inhibitor BAY11-7082 on NFκB activation. In another in vitro model of rat VSMC migration, curcumin also inhibited angiotensin II-induced VSMC migration, NFκB activation, NLRP3 expression and IL-1ß production. Intragastric administration of curcumin in SHR attenuated hypertension and reduced NFκB activation, NLRP3 and matrix metalloproteinase-9 expressions and aortic media thickness. These results indicate that curcumin inhibits VSMC migration via inhibiting NFκB-mediated NLRP3 expression in VSMC of SHR or in angiotensin II-treated VSMC. Curcumin attenuates hypertension, vascular inflammation and vascular remodeling in SHR.

4.
Bioresour Technol ; 289: 121637, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31207411

RESUMO

Interest in the resource utilization of algae has gradually increased due to the frequent occurrence of harmful algal blooms. Here, biochar derived from algae was applied to algae anaerobic fermentation for short-chain fatty acids (SCFAs) production. In the presence of algae-derived biochar, the concentration of SCFAs within 4 d (4334 mg COD/L) was approximately doubled compared to the control (2016 mg COD/L), and the fermentation time for maximal SCFAs yield was shortened. Biochar improved the disruption of algae to release more intracellular macromolecular organics. Altering algae hydrolysis, the activity of hydrolase and the contents of functional gene were advantageous to SCFAs accumulation by providing more micromolecular organics in the presence of biochar. Additionally, the relative abundance and survival of acid-forming bacteria were enhanced significantly. Furthermore, biochar accelerated the electron transport and energy synthesis in the biological system, driving the biological reactions that allow microorganisms to function and life to flourish.


Assuntos
Ácidos Graxos Voláteis , Esgotos , Anaerobiose , Carvão Vegetal , Fermentação
5.
J Cancer ; 10(4): 789-798, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854084

RESUMO

Background: Billroth I, Billroth II, Roux-en-Y, and Un-cut Roux-en-Y are common reconstruction techniques of distal gastrectomy. Which of these techniques is better has yet to be established. We performed an indirect comparison to evaluate which technique was optimal for preventing reflux symptoms. Methods: The PubMed, Cochrane Collaboration, Embase, ClinicalTrials.gov and Web of Science databases were searched to identify clinical trials that compared at least two of the reconstruction skills among Billroth I, Billroth II, Roux-en-Y, and Un-cut Roux-en-Y. Data on reflux gastritis, intraoperative blood loss, bile reflux and postoperative hospital stays were extracted from the included clinical trials for meta-analysis using a random-effects model. Results: Twenty-four articles that included 5419 individuals were assessed as eligible for meta-analysis. The indirect comparison suggested that Roux-en-Y reconstruction significantly reduces reflux gastritis, and it tended to rank first and had the highest probability of preventing bile reflux. No significant differences were found in intraoperative blood loss and postoperative hospital stays. Conclusion: This indirect comparison suggested some superiority of Roux-en-Y reconstruction after distal gastrectomy. Further perspective clinical trials are required to provide evidence for the optimal reconstruction skill.

6.
Sci Total Environ ; 658: 1131-1138, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30677977

RESUMO

Alkaline pH was beneficial for short-chain fatty acids (SCFAs) production from algae during anaerobic fermentation. This study focused on the effects of activated carbon on SCFAs production from algae during alkaline anaerobic fermentation. When activated carbon was present at 0.5 g/L, the maximum production of SCFAs was 4875 mg COD/L, which was nearly 2.4 times that of the control (2026 mg/L). Moreover, the fermentation time required for the highest SCFAs production was shortened from 6 d in the control to 4 d with activated carbon. Mechanism exploration revealed that solubilization and hydrolysis of algae as well as activities of key hydrolases and quantities of encoding genes were improved in the presence of activated carbon, which provided more proteins and carbohydrates for acid-forming bacteria. More importantly, the electron transfer among microorganisms in the algae fermentation systems was enhanced by activated carbon, contributing to improvement of the SCFAs yield and reduction of fermentation time.


Assuntos
Carvão Vegetal/química , Ácidos Graxos Voláteis/metabolismo , Microalgas/metabolismo , Microcystis/metabolismo , Anaerobiose , Fermentação
7.
J Asthma ; 56(12): 1266-1273, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30395756

RESUMO

Background: In the past few years, growing evidence supports a preventive role of vitamin D supplementation during pregnancy for wheezing or asthma in offspring. However, the optimal dose of vitamin D intake is unclear. We conducted a meta-analysis to examine the linear and nonlinear dose-response pattern of vitamin D intake during pregnancy and asthma or wheezing in offspring. Questions/purposes: The purpose of this study was to answer the following question: Which dose of vitamin D is more effective in preventing wheezing in offspring? Method: We identified relevant studies by searching PubMed, EMBASE and CENTRAL up to December 2017 and by hand-searching reference lists. Meta-analysis and subgroup analysis were performed. Fixed or random effects model linear trends analyses were conducted based on the heterogeneity test. Then, if the data did not show linear trends, we considered a nonlinear trend analysis instead. Results: A total of 6068 participants were included in the study. Our analysis showed an inverse relationship between the intake of vitamin D during pregnancy and the occurrence of wheezing in offspring (pooled OR = 0.68, 95% CI = 0.55-0.83, I2 = 24%, Z statistic = 3.64, p < 0.01). We found a nonlinear U-shaped association between vitamin D supplementation during pregnancy and asthma or wheezing in offspring, with the lowest risk at approximately 800 IU/d. Publication bias was shown in a funnel plot without Egger's test. Conclusions: Vitamin D intake during pregnancy is inversely related to wheezing or asthma in offspring. Furthermore, the trend analysis indicates that offspring may benefit from approximately 800 IU/d vitamin D intake during pregnancy.

8.
Chron Respir Dis ; 16: 1479972318790269, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30101613

RESUMO

Non-cystic fibrosis (non-CF) bronchiectasis is a condition characterized by an airway inflammatory response to bacterial pathogens. Frequent exacerbations have a major influence on the quality of life. Macrolide antibiotics have not only antibacterial but also immune-regulation effects. It is proved that macrolides have a benefit in preventing exacerbations. However, it is still uncertain whether azithromycin or erythromycin is more effective and safe. The purpose of this study was to answer the following question: Which kind of macrolide antibiotic is more effective and safe in preventing non-CF bronchiectasis exacerbation? We conducted a systematic review to identify randomized clinical trials published up to May 2017 that reported on macrolides for non-CF bronchiectasis and an adjusted indirect treatment comparison (AITC) between macrolides to evaluate their efficacy and safety. The direct comparison meta-analysis found that macrolides decreased the rate of exacerbation of non-CF bronchiectasis (risk ratio (RR) = 0.45; 95% confidence interval (CI) 0.36-0.55) with heterogeneity ( I2 = 63.7%, p = 0.064). The AITC showed that azithromycin had a significantly lower bronchiectasis exacerbation rate than erythromycin (RR = 0.35; 95% CI: 0.403-0.947). Azithromycin increased the risk of diarrhea and abnormal pain. This meta-analysis suggested that long-term treatment with macrolides significantly reduced the incidence of non-CF bronchiectasis exacerbation. Moreover, azithromycin is more efficient than roxithromycin and erythromycin in preventing exacerbation.

9.
J Biol Eng ; 12: 6, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719565

RESUMO

Background: Regenerative medicine and tissue engineering are promising approaches for organ transplantation. Extracellular matrix (ECM) based scaffolds obtained through the decellularization of natural organs have become the preferred platform for organ bioengineering. In the field of pancreas bioengineering, acellular scaffolds from different animals approximate the biochemical, spatial and vascular relationships of the native extracellular matrix and have been proven to be a good platform for recellularization and in vitro culture. However, artificial endocrine pancreases based on these whole pancreatic scaffolds have a critical flaw, specifically their difficult in vivo transplantation, and connecting their vessels to the recipient is a major limitation in the development of pancreatic tissue engineering. In this study, we focus on preparing a novel acellular extracellular matrix scaffold derived from the rat pancreatic body tail (pan-body-tail ECM scaffold). Results: Several analyses confirmed that our protocol effectively removes cellular material while preserving ECM proteins and the native vascular tree. DNA quantification demonstrated an obvious reduction of DNA compared with that of the natural organ (from 931.9 ± 267.8 to 11.7 ± 3.6 ng/mg, P < 0.001); the retention of the sGAG in the decellularized pancreas (0.878 ± 0.37) showed no significant difference from the natural pancreas (0.819 ± 0.1) (P > 0.05). After transplanted with the recellularized pancreas, fasting glucose levels declined to 9.08 ± 2.4 mmol/l within 2 h of the operation, and 8 h later, they had decreased to 4.7 ± 1.8 mmol/l (P < 0.05). Conclusions: The current study describes a novel pancreatic ECM scaffold prepared from the rat pancreatic body tail via perfusion through the left gastric artery. We further showed the pioneering possibility of in vivo circulation-connected transplantation of a recellularized pancreas based on this novel scaffold. By providing such a promising pancreatic ECM scaffold, the present study might represent a key improvement and have a positive impact on endocrine pancreas bioengineering.

11.
Bioresour Technol ; 250: 777-783, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29245128

RESUMO

Short-chain fatty acid (SCFAs) produced from harvested algae by anaerobic fermentation with uncontrolled pH was limited due to the solid cell structure of algae. This study, therefore, was undertaken to enhance the generation of SCFAs from algae by controlling the fermentation pH. pH influenced not only the total SCFAs production, but the percentage of individual SCFA. The maximal yield of SCFAs occurred at pH 10.0 and fermentation time of 6 d (3161 mg COD/L), which mainly contained acetic and iso-valeric acids and was nearly eight times that at uncontrolled pH (392 mg COD/L). Mechanism exploration revealed at alkaline pH, especially at pH 10.0, not only the cell structure of algae was damaged effectively, but also activities and relative quantification of hydrolases as well as the abundance of microorganisms responsible for organics hydrolysis and SCFAs production were improved. Also, the released microcystins from algae were removed efficiently during alkaline anaerobic fermentation.


Assuntos
Ácidos Graxos Voláteis , Esgotos , Ácidos Graxos , Fermentação , Concentração de Íons de Hidrogênio , Hidrolases , Hidrólise
12.
Biomed Pharmacother ; 98: 88-94, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29247951

RESUMO

Cervical cancer is one of the most common malignant carcinomas in the female reproductive system. Long non-coding RNAs (lncRNAs) have been verified to participate in the tumorigenesis of cervical cancer. In present study, we investigate the role of lncRNA XLOC_008466 in the occurrence and progression of cervical cancer. Results showed that XLOC_008466 expression was up-regulated in cervical cancer tissue and cells compared to normal controls. In vitro functional experiments, CCK-8 assay and colony formation assay showed that XLOC_008466 knockdown suppressed the proliferation of cervical cancer cells. Flow cytometry and transwell assay showed that XLOC_008466 knockdown induced G0/G1 phase arrest and aggravated the apoptosis. In vivo, XLOC_008466 knockdown inhibited the tumor growth. Bioinformatics analysis revealed that XLOC_008466 sponged miR-216b with the complementary binding sites at 3'-UTR. Overall, our study reveals the tumor promoting role of XLOC_008466 in cervical cancer carcinogenesis, providing a novel molecular mechanism and therapeutic target for cervical cancer.


Assuntos
Carcinogênese/genética , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Regiões 3' não Traduzidas/genética , Animais , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Fase G1/genética , Células HeLa , Humanos , Camundongos , Camundongos Nus , Fase de Repouso do Ciclo Celular/genética , Regulação para Cima/genética
13.
Exp Ther Med ; 14(4): 3851-3855, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29042991

RESUMO

Diabetes mellitus (DM)-induced high blood sugar severely damages vascular endothelial cells (VECs), which are in direct contact with the blood. Diabetic complications cause difficulties in skin wound healing and VECs are important for this process. Previous studies demonstrated that high blood sugar delayed the repair of wounded VECs, but the underlying mechanism has remained elusive. To explore the effects of diabetic conditions on VEC damage, cells were incubated in a medium with high glucose and then subjected to RNA-sequencing based transcriptome analysis. The results revealed that numerous biological processes were altered by HG stress, including extracellular matrix-receptor interaction, NOD-like receptor signaling and the nuclear factor (NF)-κB pathway. HG treatment increased the levels of phosphorylated inhibitor of NF-κB (IκB-α), the key NF-κB signaling regulator as well as the transcripts of plasminogen activator inhibitor-1 and interleukin-8, two inflammatory response markers. Treatment with extracellular signal-regulated kinase (ERK)- and c-Jun N-terminal kinase (JNK)-specific inhibitors U0126 and sp600125, respectively, led to the activation of IκB-α; however, the inhibitor of IκBα phosphorylation Bay11-7082 did not affect ERK and JNK activity, suggesting that ERK/JNK signaling occurs upstream of NF-κB in VECs. The present study provided useful information regarding the effects of diabetes on VECs, which may provide approaches for therapies of diabetes-associated complications in the future.

14.
Cell Death Dis ; 8(10): e3074, 2017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28981106

RESUMO

Inflammation is involved in pathogenesis of hypertension. NLRP3 inflammasome activation is a powerful mediator of inflammatory response via caspase-1 activation. The present study was designed to determine the roles and mechanisms of NLRP3 inflammasome in phenotypic modulation and proliferation of vascular smooth muscle cells (VSMCs) in hypertension. Experiments were conducted in spontaneously hypertensive rats (SHR) and primary aortic VSMCs. NLRP3 inflammasome activation was observed in the media of aorta in SHR and in the VSMCs from SHR. Knockdown of NLRP3 inhibited inflammasome activation, VSMC phenotypic transformation and proliferation in SHR-derived VSMCs. Increased NFκB activation, histone acetylation and histone acetyltransferase expression were observed in SHR-derived VSMCs and in media of aorta in SHR. Chromatin immunoprecipitation analysis revealed the increased histone acetylation, p65-NFκB and Pol II occupancy at the NLRP3 promoter in vivo and in vitro. Inhibition of NFκB with BAY11-7082 or inhibition of histone acetyltransferase with curcumin prevented the NLRP3 inflammasome activation, VSMC phenotype switching and proliferation in VSMCs from SHR. Moreover, curcumin repressed NFκB activation. Silencing of NLRP3 gene ameliorated hypertension, vascular remodeling, NLRP3 inflammasome activation and phenotype switching in the aorta of SHR. These results indicate that NLRP3 inflammasome activation response to histone acetylation and NFκB activation contributes to VSMC phenotype switching and proliferation and vascular remodeling in hypertension.


Assuntos
Proliferação de Células/genética , Hipertensão/genética , Inflamassomos/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Angiotensina II/genética , Animais , Caspase 1/genética , Curcumina/administração & dosagem , Regulação da Expressão Gênica , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , NF-kappa B/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fenótipo , Ratos , Ratos Endogâmicos SHR/genética , Ratos Endogâmicos SHR/metabolismo , Transdução de Sinais
17.
PLoS One ; 12(3): e0173410, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28306739

RESUMO

ICD-10(International Classification of Diseases 10th revision) is a classification of a disease, symptom, procedure, or injury. Diseases are often described in patients' medical records with free texts, such as terms, phrases and paraphrases, which differ significantly from those used in ICD-10 classification. This paper presents an improved approach based on the Longest Common Subsequence (LCS) and semantic similarity for automatic Chinese diagnoses, mapping from the disease names given by clinician to the disease names in ICD-10. LCS refers to the longest string that is a subsequence of every member of a given set of strings. The proposed method of improved LCS in this paper can increase the accuracy of processing in Chinese disease mapping.


Assuntos
Algoritmos , Classificação Internacional de Doenças , Humanos
18.
J Cell Mol Med ; 20(5): 903-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26820236

RESUMO

UNLABELLED: Xeroderma pigmentosum group G (XPG) protein plays an important role in the DNA repair process by cutting the damaged DNA at the 3' terminus. Previous studies have indicated some polymorphisms in the XPG gene are associated with stomach cancer susceptibility. We performed this hospital-based case-control study to evaluate the association of four potentially functional XPG polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C and rs873601G>A) with stomach cancer susceptibility. The four single nucleotide polymorphisms (SNPs) were genotyped in 692 stomach cancer cases and 771 healthy controls. Logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association of interest. Of the studied SNPs, XPG rs873601G>A polymorphism was found to significantly associate with stomach cancer susceptibility (AA versus GG/AG: OR = 1.31, 95% CI = 1.03-1.66, P = 0.027). Combined analysis of all SNPs revealed that the individuals with two of risk genotypes had a significantly increased stomach cancer risk (OR = 1.52, 95% CI = 1.13-2.06). In the stratification analysis, the association between the rs873601AA genotype and stomach cancer risk was observed in older group (>59 year), as well as patients with non-cardia stomach cancer. Further combined analysis indicated men, smokers, or non-drinkers more than one risk genotypes had a significantly increased stomach cancer risk. Our results indicate that XPG rs873601G>A polymorphism may be associated with the risk of stomach cancer. Further prospective studies with different ethnicities and large sample sizes are needed to validate our findings.


Assuntos
Proteínas de Ligação a DNA/genética , Endonucleases/genética , Predisposição Genética para Doença , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Expressão Gênica , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/patologia
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 32(1): 25-31, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25997261

RESUMO

To explore the self-organization robustness of the biological neural network, and thus to provide new ideas and methods for the electromagnetic bionic protection, we studied both the information transmission mechanism of neural network and spike timing-dependent plasticity (STDP) mechanism, and then investigated the relationship between synaptic plastic and adaptive characteristic of biology. Then a feedforward neural network with the Izhikevich model and the STDP mechanism was constructed, and the adaptive robust capacity of the network was analyzed. Simulation results showed that the neural network based on STDP mechanism had good rubustness capacity, and this characteristics is closely related to the STDP mechanisms. Based on this simulation work, the cell circuit with neurons and synaptic circuit which can simulate the information processing mechanisms of biological nervous system will be further built, then the electronic circuits with adaptive robustness will be designed based on the cell circuit.


Assuntos
Modelos Neurológicos , Rede Nervosa , Potenciais de Ação , Plasticidade Neuronal , Neurônios
20.
PLoS One ; 10(2): e0117576, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25658482

RESUMO

BACKGROUND: Several genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs). METHODS: To evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings. RESULTS: In the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07-1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03-1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02-1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00-1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15-1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14-1.84), respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60-0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03-1.64), when compared with those having 0-1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer. CONCLUSIONS: This study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.


Assuntos
Antígenos de Neoplasias/genética , Mucina-1/genética , Proteínas de Neoplasias/genética , Fosfoinositídeo Fosfolipase C/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Proteínas Ligadas por GPI/genética , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/patologia , Adulto Jovem
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