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1.
Nat Commun ; 10(1): 4957, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673082

RESUMO

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.

2.
Nutrients ; 11(8)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398891

RESUMO

The purpose of this study was to investigate the associations between intakes of fibre from the main food sources of fibre in the UK diet with body mass index (BMI), percentage body fat (%BF), waist circumference (WC) and C-reactive protein (CRP). Participants enrolled in the Airwave Health Monitoring Study (2007-2012) with 7-day food records (n = 6898; 61% men) were included for cross-sectional analyses. General linear models evaluated associations across fifths of fibre intakes (total, vegetable, fruit, potato, whole grain and non-whole grain cereal) with BMI, %BF, WC and CRP. Fully adjusted analyses showed inverse linear trends across fifths of total fibre and fibre from fruit with all outcome measures (ptrend < 0.0001). Vegetable fibre intake showed an inverse association with WC (ptrend 0.0156) and CRP (ptrend 0.0005). Fibre from whole grain sources showed an inverse association with BMI (ptrend 0.0002), %BF (ptrend 0.0007) and WC (ptrend 0.0004). Non-whole grain cereal fibre showed an inverse association with BMI (Ptrend 0.0095). Direct associations observed between potato fibre intake and measures of body composition and inflammation were attenuated in fully adjusted analyses controlling for fried potato intake. Higher fibre intake has a beneficial association on body composition, however, there are differential associations based on the food source.

3.
Biochim Biophys Acta Rev Cancer ; 1872(2): 188311, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31442475

RESUMO

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a group of rare tumors that are increasing in prevalence. The complex tumor immune microenvironment (TIME) plays an important role in tumor development and the response to immunotherapy but is poorly understood. In this review, the components of the TIME are described in detail, including discussion about infiltrating immune cells, the immune checkpoint system, the cytokine and chemokine milieu, and immunomodulatory factors. Moreover, a comparison between TIMEs among different types of GEP-NENs and the interplay among the TIME, tumor cells, and the stromal microenvironment is described. Novel treatment options for GEP-NENs and potential biomarkers for the immune response are also characterized. We provide a comprehensive generalized review of the TIME that can inform GEP-NEN treatment strategies.


Assuntos
Tumores Neuroendócrinos/imunologia , Neoplasias Pancreáticas/imunologia , Neoplasias Gástricas/imunologia , Animais , Antineoplásicos Imunológicos/uso terapêutico , Ensaios Clínicos como Assunto , Citocinas/metabolismo , Humanos , Fatores Imunológicos/metabolismo , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Evasão Tumoral , Microambiente Tumoral
4.
Zhongguo Zhen Jiu ; 39(7): 685-8, 2019 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-31286727

RESUMO

OBJECTIVE: To observe the therapeutic effect of acupuncture on blood pressure variability (BPV) in elderly patients with cerebral infarction complicated with essential hypertension. METHODS: Seventy-six elderly patients with cerebral infraction complicated with essential hypertension were randomized into an observation group and a control group, 38 cases in each group. Xingnao Kaiqiao acupuncture and nifedipin were given in the control group. On the basis treatment in the control group, the Huoxue Sanfeng and Tiaohe Ganpi acupuncture was applied at Renying (ST 9), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36) and Taichong (LR 3) in the observation group for 30 min. The treatment was given once a day, 5 times a week for 8 weeks. The 24-hour ambulatory blood pressure was monitored in the two groups. The changes of blood pressure and blood pressure variability were observed before and after 8 weeks of treatment, and the occurrence of adverse reactions during the treatment were recorded. RESULTS: The mean systolic blood pressure (SBP), diastolic blood pressure (DBP), daytime SBP, DBP, nighttime SBP and DBP were reduced in the two groups after 8 weeks of treatment (P<0.05), and the results in the observation group were lower than those in the control group (P<0.05). After 8 weeks of treatment, the daytime, nighttime, 24 h systolic blood pressure variability (SBPV) and diastolic blood pressure variability (DBPV) in the observation group were lower than those before treatment (P<0.05), there was no significant difference between before and after treatment in the control group (P>0.05). CONCLUSION: Huoxue Sanfeng and Tiaohe Ganpi acupuncture method can effectively control the blood pressure and blood pressure variability in the elderly patients with cerebral infraction complicated with essential hypertension.


Assuntos
Terapia por Acupuntura , Infarto Cerebral , Hipertensão , Idoso , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Infarto Cerebral/complicações , Humanos , Hipertensão/complicações
5.
Nat Hum Behav ; 3(9): 950-961, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31358974

RESUMO

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.

6.
Appl Microbiol Biotechnol ; 103(17): 7151-7160, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250059

RESUMO

10-hydroxy-cis-12 octadecenoic acid (10-HOE) is a type of octadecenoic acid with a hydroxyl on the C10 carbon. It is generated from linoleic acid (LA) catalyzed by linoleate hydratase in lactobacilli, which was initially named as myosin-cross-reactive antigen (MCRA). In lactobacilli, 10-HOE is the first intermediate in the production of conjugated LA (CLA). Although MCRA from bifidobacteria can generate 10-HOE, the precise role of 10-HOE in CLA production in bifidobacteria remains unknown. In the current work, 10-HOE and LA were added to the medium as the substrate both separately and synchronously to analyze their influence on CLA production. Using 10-HOE as the substrate, bifidobacteria were able to generate CLA by first converting it to LA, followed by CLA accumulation. Recombinant MCRA catalyzed the conversion of 10-HOE to LA, indicating that bifidobacterial MCRA can account for the reversible conversion between LA and 10-HOE. This is the first report to demonstrate the precise role of 10-HOE in the process of CLA production among bifidobacteria.

7.
Food Res Int ; 121: 367-378, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31108759

RESUMO

The effect of Lactobacillus plantarum-fermentation on the anti-diabetic functionality of Momordica charantia was examined using a high-fat-diet and low-dose streptozocin-induced type 2 diabetic rat model. Fermented Momordica charantia juice (FMCJ) administration mitigated the hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress in diabetic rats more favorably than the non-fermented counterpart. Treatments with FMCJ improved ergosterols and lysomonomethyl-phosphatidylethanolamines metabolisms more effectively. Supplement of FMCJ regulated the composition of the gut microbiota, such as increased the abundance of Bacteroides caecigallinarum, Oscillibacter ruminantium, Bacteroides thetaiotaomicron, Prevotella loescheii, Prevotella oralis, and Prevotella melaninogenica, in diabetic rats compared with untreated diabetic rats. Moreover, FMCJ-treated diabetic rats exhibited higher concentrations of acetic acid, propionic acid, butyric acid, total short-chain fatty acids and lower pH values in colonic contents than that in non-fermented juice-treated rats. These results demonstrated that Lactobacillus plantarum-fermentation enhanced the anti-diabetic property of MC juice by favoring the regulation of gut microbiota and the production of SCFAs.

8.
Environ Res ; 175: 148-155, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31125718

RESUMO

BACKGROUND: Terrestrial Trunked Radio (TETRA) is used for radiocommunications among the British police forces. OBJECTIVES: To investigate association of personal radio use and sickness absence among police officers and staff from the Airwave Health Monitoring Study. METHODS: Participant-level sickness absence records for 26 forces were linked with personal radio use for 32,102 participants. We used multivariable logistic regression to analyse TETRA usage in year prior to enrolment and sickness absence (lasting more than 7 or 28 consecutive days) in the following year and a zero-inflated negative binomial model for analyses of number of sickness absence episodes of any duration ('spells') over the same period. In secondary analyses, we looked at an extended period of observation among a sub-cohort with linked data over time, using Cox proportional hazards regression. RESULTS: Median personal radio use (year prior to enrolment) was 29.7 min per month (interquartile range 7.5, 64.7) among users. In the year following enrolment there were 25,655 sickness absence spells among 15,248 participants. There were similar risks of sickness absence lasting more than seven days among users and non-users, although among users risk was higher with greater use, odds ratio = 1.04 (95% confidence interval [CI] 1.02 to 1.06) per doubling of radio use. There was no association for sickness absence of more than 28 days. For sickness absence spells, risk was lower among users than non-users (incidence rate ratio = 0.91; 95% CI 0.75 to 1.11), again with higher risk among users for greater radio use. There was no association between radio use and sickness absence in secondary analyses. DISCUSSION: There were similar or lower risks of sickness absence in TETRA radio users compared with non-users. Among users, the higher risk of sickness absence with greater radio use may reflect working pattern differences among police personnel rather than effects of radiofrequency exposure.

9.
PLoS Genet ; 15(4): e1008065, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30946745

RESUMO

Integration of environmental and endogenous cues at plant shoot meristems determines the timing of flowering and reproductive development. The MADS box transcription factor FLOWERING LOCUS C (FLC) of Arabidopsis thaliana is an important repressor of floral transition, which blocks flowering until plants are exposed to winter cold. However, the target genes of FLC have not been thoroughly described, and our understanding of the mechanisms by which FLC represses transcription of these targets and how this repression is overcome during floral transition is still fragmentary. Here, we identify and characterize TARGET OF FLC AND SVP1 (TFS1), a novel target gene of FLC and its interacting protein SHORT VEGETATIVE PHASE (SVP). TFS1 encodes a B3-type transcription factor, and we show that tfs1 mutants are later flowering than wild-type, particularly under short days. FLC and SVP repress TFS1 transcription leading to deposition of trimethylation of Iysine 27 of histone 3 (H3K27me3) by the Polycomb Repressive Complex 2 at the TFS1 locus. During floral transition, after downregulation of FLC by cold, TFS1 transcription is promoted by SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1), a MADS box protein encoded by another target of FLC/SVP. SOC1 opposes PRC function at TFS1 through recruitment of the histone demethylase RELATIVE OF EARLY FLOWERING 6 (REF6) and the SWI/SNF chromatin remodeler ATPase BRAHMA (BRM). This recruitment of BRM is also strictly required for SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 9 (SPL9) binding at TFS1 to coordinate RNAPII recruitment through the Mediator complex. Thus, we show that antagonistic chromatin modifications mediated by different MADS box transcription factor complexes play a crucial role in defining the temporal and spatial patterns of transcription of genes within a network of interactions downstream of FLC/SVP during floral transition.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Proteínas de Domínio MADS/genética , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Cromatina/genética , Cromatina/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Código das Histonas/genética , Proteínas de Domínio MADS/metabolismo , Meristema/genética , Meristema/crescimento & desenvolvimento , Meristema/metabolismo , Modelos Biológicos , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Plantas Geneticamente Modificadas , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
Neuropeptides ; 75: 18-24, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30922523

RESUMO

The corticotropin-releasing factor (CRF) related peptides system has widespread distributions in central nervous system, to perform many physiological and pathophysiological functions, including cardiovascular functions. A complex connection exists between the central CRF related peptides system and cardiovascular system. There are multiple pathways and mechanisms through which the central CRF related peptides system influences cardiovascular functions. A dysfunction in the central CRF related peptides system may lead to a wide range of alterations in cardiovascular functions. Though there are difficulties or limitations in establishing exact modulatory roles of the central CRF related peptides system in cardiovascular functions. The central CRF related peptides system as target to prevent cardiovascular diseases is being pursued with increasing interest. In this review, we summarize recent understanding on cardiovascular functions of the CRF related peptides system in limbic forebrain, hypothalamus and brain stem structures, discuss mechanisms of the central CRF related peptides system in control of cardiovascular functions, and suggest that the central CRF related peptides system may be a potent candidate for prevention of cardiovascular diseases.

11.
Cereb Cortex ; 29(4): 1736-1751, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30721969

RESUMO

Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-κB activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 × 10-19) and regional methylation (P = 5.90 × 10-25). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-κB. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.

12.
Sleep Breath ; 23(2): 719-728, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30783913

RESUMO

OBJECTIVES: To determine inter-lab reliability in sleep stage scoring using the 2014 American Academy of Sleep Medicine (AASM) manual. To understand in-depth reasons for disagreement and provide suggestions for improvement. METHODS: This study consisted of 40 all-night polysomnographys (PSGs) from different samples. PSGs were segmented into 37,642 30-s epochs. Five doctors from China and two doctors from America scored the epochs following the 2014 AASM standard. Scoring disagreement between two centers was evaluated using Cohen's kappa (κ). After visual inspection of PSGs of deviating scorings, potential disagreement reasons were analyzed. RESULTS: Inter-lab reliability yielded a substantial degree (κ = 0.75 ± 0.01). Scoring for stage W (κ = 0.89) and R (κ = 0.87) achieved the highest agreement, while stage N1 (κ = 0.45) reflected the lowest. Considering the relative disagreement ratio, N2-N3 (22.09%), W-N1 (19.68%), and N1-N2 (18.75%) were the most frequent combinations of discrepancy. American and Chinese doctors showed certain characteristics in the scoring of discrepancy combination W-N1, N1-N2, and N2-N3. There are seven reasons for disagreement, namely "on-threshold characteristic" (29.21%), "context influence" (18.06%), "characteristic identification difficulty" (8.81%), "arousal-wake confusion" (7.57%), "derivation inconsistence" (2.15%), "on-borderline characteristic" (0.92%), and "misrecognition" (33.27%). CONCLUSIONS: This study demonstrated the sleep stage scoring agreement of the 2014 AASM manual and explored potential sources of labeling ambiguity. Improvement measures were suggested accordingly to help remove ambiguity for scorers and improve scoring reliability at the international level.

13.
Am J Hum Genet ; 104(1): 112-138, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30595373

RESUMO

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E-04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E-03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E-06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.


Assuntos
DNA Mitocondrial/genética , Genes Mitocondriais/genética , Variação Genética/genética , Metabolismo/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Adipócitos/metabolismo , Índice de Massa Corporal , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Estudos de Coortes , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Glucose/metabolismo , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/metabolismo , Locos de Características Quantitativas , Relação Cintura-Quadril
14.
Food Funct ; 10(1): 448-457, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30628614

RESUMO

Momordica charantia (M. charantia) has been widely used to treat obesity due to its bioactive ingredients. This research aimed to investigate the anti-obesity effect of polysaccharides (FP) from fermented M. charantia with Lactobacillus plantarum NCU116 on high-fat induced obese rats. We found that FP could effectively lower the body weight gain, Lee's index, insulin resistance and cell sizes of epididymal adipose tissues in obese rats compared with polysaccharides from non-fermented M. charantia (NFP). FP treatments decreased the total cholesterol, triacylglycerols, and low-density lipoprotein cholesterol, leptin, whereas they elevated the high-density lipoprotein cholesterol, adiponectin, significantly in the serum of obese rats. Furthermore, administrations of FP notably improved oxidative balance in obese rats. Lipidomics results indicated that 24 potential biomarkers have been identified in serum. Additionally, 21 lipids were considerably altered by FP and NFP intakes, such as fatty acyls, glycerolipids, sphingolipids, sterol lipids and glycerophospholipids. The anti-obesity properties of FP were revealed via relieving insulin resistance and fat accumulation of obese rats, which was associated with the regulation of lipid metabolism. Overall, FP exerted more favourable impacts on the anti-obesity effect than NFP, which may be attributed to fermentation.


Assuntos
Lactobacillus plantarum/metabolismo , Momordica charantia/química , Momordica charantia/microbiologia , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fermentação , Humanos , Resistência à Insulina , Masculino , Momordica charantia/metabolismo , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/metabolismo , Polissacarídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
15.
Br J Cancer ; 120(3): 375-378, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30585256

RESUMO

BACKGROUND: Radiofrequency electromagnetic fields (RF-EMF) from mobile phones have been classified as potentially carcinogenic. No study has investigated use of Terrestrial Trunked Radio (TETRA), a source of RF-EMF with wide occupational use, and cancer risks. METHODS: We investigated association of monthly personal radio use and risk of cancer using Cox proportional hazards regression among 48,518 police officers and staff of the Airwave Health Monitoring Study in Great Britain. RESULTS: During median follow-up of 5.9 years, 716 incident cancer cases were identified. Among users, the median of the average monthly duration of use in the year prior to enrolment was 30.5 min (inter-quartile range 8.1, 68.1). Overall, there was no association between personal radio use and risk of all cancers (hazard ratio [HR] = 0.98, 95% confidence interval [CI]: 0.93, 1.03). For head and neck cancers HR = 0.72 (95% CI: 0.30, 1.70) among personal radio users vs non-users, and among users it was 1.06 (95% CI: 0.91, 1.23) per doubling of minutes of personal radio use. CONCLUSIONS: With the limited follow-up to date, we found no evidence of association of personal radio use with cancer risk. Continued follow-up of the cohort is warranted.


Assuntos
Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/efeitos adversos , Neoplasias de Cabeça e Pescoço/epidemiologia , Ondas de Rádio/efeitos adversos , Telefone Celular , Grupos Étnicos , Feminino , Neoplasias de Cabeça e Pescoço/etiologia , Humanos , Masculino , Polícia , Reino Unido/epidemiologia
16.
Eur J Surg Oncol ; 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30416079

RESUMO

INTRODUCTION: Arpin (Arp2/3 complex inhibitor), a novel protein found in 2013, plays a pivotal role in cell motility and migration. However, the prognostic value of Arpin in pancreatic ductal adenocarcinoma (PDAC) remains unknown. MATERIALS AND METHODS: We analyzed the gene expression of ARPIN using the GEO dataset (GSE71989) and validated the results by immunohistochemistry (IHC) and Western blot in our clinical database. Tissue microarray specimens from 214 patients who underwent curative pancreatectomy for PDAC were used. The tumors that expressed high and low levels of Arpin were compared with patient outcome using Kaplan-Meier curves and the multivariate Cox proportional hazard regression model. IHC was then used in 43 paired primary tumor tissues and metastasis tissues to detect the expression of Arpin. RESULTS: Arpin had low expression in the tumor tissue compared with the paracancerous tissue in PDAC. Patients with low intratumoral Arpin expression had worse overall survival (OS) and recurrence-free survival (RFS) than patients with high expression in the training set (p < 0.001, p < 0.001) and validation set (p < 0.001, p < 0.001). The multivariate analysis revealed that the 8th edition TNM stage and Arpin expression were independent prognostic factors associated with OS and RFS in the training and validation sets, respectively. Arpin had lower expression in the metastasis tissues than in the primary tumors of patients with PDAC (p = 0.048). CONCLUSION: The Arpin level is an independent prognostic factor that can be a potential predictor to aid in the management of PDAC.

18.
Ann Surg Oncol ; 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30374923

RESUMO

BACKGROUND: Tumor-infiltrating neutrophils (TINs) indicate poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC). Activated neutrophils can generate neutrophil extracellular traps (NETs). Little is known about the presence and prognostic significance of tumor-infiltrating NETs in PDAC. METHODS: This study enrolled 317 patients, in two independent sets (training and validation), who underwent curative pancreatectomy for PDAC in Shanghai Cancer Center. TINs and NETs were identified by immunohistochemical staining for CD15 and citrullinated histone H3, respectively. The relationship between clinicopathological features and outcomes was analyzed. Accuracy of prognostic prediction models was evaluated using concordance index (C-index) and Akaike information criterion (AIC). RESULTS: NETs were associated with OS (both, P < 0.001) and RFS (both, P < 0.001) in the training and validation sets. Tumor-infiltrating NETs predicted poor postsurgical survival of patients with PDAC. Moreover, multivariate analysis identified NETs and AJCC TNM stage as two independent prognostic factors for OS and RFS. Combination of NETs with the 8th edition TNM staging system (C-index, 0.6994 and 0.6669, respectively; AIC, 1067 and 1126, respectively) generated a novel model that improved the predictive accuracy for survival in both sets (C-index, 0.7254 and 0.7117, respectively; AIC, 1047 and 1102, respectively). The model combining presence of NETs with the 7th edition AJCC TNM staging system also had improved predictive accuracy. CONCLUSIONS: NETs were an independent prognostic factor in PDAC and incorporation of NETs along with the standard TNM stating system refined risk-stratification and predicted survival in PDAC with improved accuracy.

19.
Comput Biol Med ; 103: 71-81, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30342269

RESUMO

BACKGROUND: Automatic sleep stage classification is essential for long-term sleep monitoring. Wearable devices show more advantages than polysomnography for home use. In this paper, we propose a novel method for sleep staging using heart rate and wrist actigraphy derived from a wearable device. METHODS: The proposed method consists of two phases: multi-level feature learning and recurrent neural networks-based (RNNs) classification. The feature learning phase is designed to extract low- and mid-level features. Low-level features are extracted from raw signals, capturing temporal and frequency domain properties. Mid-level features are explored based on low-level ones to learn compositions and structural information of signals. Sleep staging is a sequential problem with long-term dependencies. RNNs with bidirectional long short-term memory architectures are employed to learn temporally sequential patterns. RESULTS: To better simulate the use of wearable devices in the daily scene, experiments were conducted with a resting group in which sleep was recorded in the resting state, and a comprehensive group in which both resting sleep and non-resting sleep were included. The proposed algorithm classified five sleep stages (wake, non-rapid eye movement 1-3, and rapid eye movement) and achieved weighted precision, recall, and F1 score of 66.6%, 67.7%, and 64.0% in the resting group and 64.5%, 65.0%, and 60.5% in the comprehensive group using leave-one-out cross-validation. Various comparison experiments demonstrated the effectiveness of the algorithm. CONCLUSIONS: Our method is efficient and effective in scoring sleep stages. It is suitable to be applied to wearable devices for monitoring sleep at home.

20.
J Cancer ; 9(18): 3417-3426, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271504

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer. The 5-year survival rate for PDAC remains low because it is always diagnosed at an advanced stage and it is resistant to therapy. A biomarker, which could detect asymptomatic premalignant or early malignant tumors and predict the response to treatment, will benefit patients with PDAC. However, traditional biopsy has its limitations. There is an urgent need for a tumor biomarker that could easily and repeatedly sample and monitor, in real time, the progress of tumor development. Liquid biopsy could be a tool to assess potential biomarkers. In this review, we focused on the latest discoveries and advancements of liquid biopsy technology in pancreatic cancer research and demonstrated how this technology is being used in clinical applications.

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