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1.
Nat Commun ; 12(1): 6388, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737258

RESUMO

The relationship between dietary factors and liver disease remains poorly understood. This study evaluated the associations of whole grain and dietary fiber intake with liver cancer risk and chronic liver disease mortality. The National Institutes of Health-American Association of Retired Persons Diet and Health Study cohort recruited 485, 717 retired U.S. participants in 1995-1996. Follow-up through 2011 identified 940 incident liver cancer cases and 993 deaths from chronic liver disease. Compared with the lowest, the highest quintile of whole grain intake was associated with lower liver cancer risk (Hazard ratio [HR]Q5 vs. Q1 = 0.78, 95% confidence interval [CI]: 0.63-0.96) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.44, 95% CI: 0.35-0.55) in multivariable Cox models. Dietary fiber was also associated with lower liver cancer risk (HRQ5 vs. Q1 = 0.69, 95% CI: 0.53-0.90) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.37, 95% CI: 0.29-0.48). Fiber from vegetables, beans and grains showed potential protective effect. Here, we show that higher intake of whole grain and dietary fiber are associated with lower risk of liver cancer and liver disease mortality.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34791515

RESUMO

Mupirocin, a polyketide antibiotic produced by Pseudomonas fluorescens, is used as a topical antimicrobial treatment to cure various skin infections. Quorum sensing system plays an important role in regulation of mupirocin biosynthesis in P. fluorescens NCIMB 10586. In Pseudomonas, the RpeA/RpeB two-component signal transduction (TCST) system regulates quorum sensing system. However, the influences of the RpeA/RpeB TCST system on mupirocin production or other cell activities have not been studied. In this work, the homologous genes of rpeA and rpeB in P. fluorescens NCIMB 10586 were identified and inactivated in the chromosome, respectively. The deletion of rpeA reduced the mupirocin production from 160 in the wild-type to 21.3 mg/L along with slightly decreased cell growth, while no significant effected on mupirocin production in the rpeB mutant. Next, it was found that the RpeA/RpeB TCST system regulated the biosynthesis of mupirocin by modulating the quorum sensing system. Furthermore, untargeted metabolomics analysis was employed to detect the influences of RpeA on other cell activities modulated by quorum sensing system. Combined with quantitative real-time PCR, the results demonstrated that RpeA also regulated other cell activities including central carbon, amino acids, fatty acids, and purine metabolism. Overall, this study expands the current understanding of the RpeA/RpeB TCST system and provides several targets for increasing yields of mupirocin. KEY POINTS: • In P. fluorescens, the RpeA/RpeB TCST system regulates the biosynthesis of mupirocin. • RpeA modulates the cell activities through effecting the central carbon metabolism.

3.
Front Nutr ; 8: 690428, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616762

RESUMO

Background: Dietary patterns promoting hyperinsulinemia and chronic inflammation, including the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP), have been shown to strongly influence risk of weight gain, type 2 diabetes, cardiovascular disease, and cancer. EDIH was developed using plasma C-peptide, whereas EDIP was based on plasma C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha receptor 2 (TNF-αR2). We investigated whether these dietary patterns were associated with a broader range of relevant biomarkers not previously tested. Methods: In this cross-sectional study, we included 35,360 women aged 50-79 years from the Women's Health Initiative with baseline (1993-1998) fasting blood samples. We calculated EDIH and EDIP scores from baseline food frequency questionnaire data and tested their associations with 40 circulating biomarkers of insulin response/insulin-like growth factor (IGF) system, chronic systemic inflammation, endothelial dysfunction, lipids, and lipid particle size. Multivariable-adjusted linear regression was used to estimate the percent difference in biomarker concentrations per 1 standard deviation increment in dietary index. FDR-adjusted p < 0.05 was considered statistically significant. Results: Empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) were significantly associated with altered concentrations of 25 of the 40 biomarkers examined. For EDIH, the percent change in biomarker concentration in the insulin-related biomarkers ranged from +1.3% (glucose) to +8% (homeostatic model assessment for insulin resistance) and -9.7% for IGF-binding protein-1. EDIH impacted inflammation and endothelial dysfunction biomarkers from +1.1% (TNF-αR2) to +7.8% (CRP) and reduced adiponectin by 2.4%; and for lipid biomarkers: +0.3% (total cholesterol) to +3% (triglycerides/total cholesterol ratio) while reducing high-density lipoprotein cholesterol by 2.4%. EDIP showed a similar trend of associations with most biomarkers, although the magnitude of association was slightly weaker for the insulin-related biomarkers and stronger for lipids and lipid particle size. Conclusions: Dietary patterns with high potential to contribute to insulin hypersecretion and to chronic systemic inflammation, based on higher EDIH and EDIP scores, were associated with an unfavorable profile of circulating biomarkers of glucose-insulin dysregulation, chronic systemic inflammation, endothelial dysfunction and dyslipidemia. The broad range of biomarkers further validates EDIH and EDIP as mechanisms-based dietary patterns for use in clinical and population-based studies of metabolic and inflammatory diseases.

4.
J Mol Cell Biol ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34529077

RESUMO

Clustered protocadherins (Pcdhs) are a large family of cadherin-like cell adhesion proteins that are central for neurite self-avoidance and neuronal connectivity in the brain. Their downstream non-receptor tyrosine kinase Pyk2 (proline-rich tyrosine kinase 2, also known as Ptk2b, Cakb, Raftk, Fak2, and Cadtk) is predominantly expressed in the hippocampus. We constructed Pyk2 null mouse lines and found that these mutant mice showed enhancement in contextual fear memory, without any change in auditory-cued and spatial-referenced learning and memory. In addition, by preparing Y402F mutant mice, we observed that Pyk2 suppressed contextual fear memory in an autophosphorylation-independent manner. Moreover, using high-throughput RNA sequencing, we found that immediate early genes, such as Npas4, cFos, Zif268/Egr1, Arc, and Nr4a1, were enhanced in Pyk2 null mice. We further showed that Pyk2 disruption affected pyramidal neuronal complexity and spine dynamics. Thus, we demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2 null mice provide a model for understanding fear-related disorders. These findings have interesting implications regarding dysregulation of the Pcdh‒Pyk2 axis in neuropsychiatric disorders.

5.
iScience ; 24(9): 103031, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34541467

RESUMO

Ultrathin hexagonal GaTe, with relatively high charge density, holds great potential in the field of optoelectronic devices. However, the thermodynamical stability limits it fabrications as well as applications. Here, by introducing two-dimensional MoS2 as the substrate, we successfully realized the phase-controlled synthesis of ultrathin h-GaTe, leading to high-quality h-GaTe/MoS2 heterostructures. Theoretical calculation studies reveal that GaTe with hexagonal phase is more thermodynamically stable on MoS2 templates, which can be attributed to the strain stretching and the formation energy reduction. Based on the achieved p-n heterostructures, optoelectronic devices are designed and probed, where remarkable photoresponsivity (32.5 A/W) and fast photoresponse speed (<50 µs) are obtained, indicating well-behaved photo-sensing behaviors. The study here could offer a good reference for the controlled growth of the relevant materials, and the achieved heterostructure will find promising applications in future integrated electronic and optoelectronic devices and systems.

6.
Am J Clin Nutr ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582546

RESUMO

BACKGROUND: The associations between nut consumption and cancer risk have not been extensively investigated. OBJECTIVES: We aimed to examine the associations between nut consumption, especially specific types of nuts (peanut, tree nut, walnut, and tree nut other than walnut), and cancer risk. METHODS: Nut consumption was assessed by FFQ at baseline and updated every 2-4 y in the Nurses' Health Study (1980-2014), the Nurses' Health Study II (1991-2015), and the Health Professionals Follow-up Study (1986-2018). We examined the associations between the intake of total and specific types of nuts and risk of total cancer and common cancers, including lung, colorectal, breast, bladder, and aggressive prostate cancer. Cox proportional-hazards models were used to obtain the HRs and 95% CIs in each cohort as well as pooled. RESULTS: During 5,873,671 person-years of follow-up in 180,832 women and 45,560 men, we documented 44,561 incident cancer cases. As compared with nonconsumers, the pooled multivariable HRs of total nut consumption for ≥5 times/wk were 0.99 (95% CI: 0.94, 1.04; P-trend = 0.54) for total cancer, 0.88 (95% CI: 0.74, 1.04; P-trend = 0.18) for lung cancer, 1.07 (95% CI: 0.92, 1.26; P-trend = 0.89) for colorectal cancer, 0.90 (95% CI: 0.71, 1.14; P-trend = 0.65) for bladder cancer, 0.96 (95% CI: 0.85, 1.08; P-trend = 0.36) for breast cancer, and 1.18 (95% CI: 0.92, 1.51; P-trend = 0.52) for aggressive prostate cancer. CONCLUSIONS: In 3 large prospective cohorts, frequent nut consumption was not associated with risk of total cancer and common individual cancers.

7.
Molecules ; 26(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34361645

RESUMO

The deficiency of available silicon (Si) incurred by year-round agricultural and horticultural practices highlights the significance of Si fertilization for soil replenishment. This study focuses on a novel and economical route for the synthesis of Si fertilizer via the calcination method using talc and calcium carbonate (CaCO3) as starting materials. The molar ratio of talc to CaCO3 of 1:2.0, calcination temperature of 1150 °C and calcination time of 120 min were identified as the optimal conditions to maximize the available Si content of the prepared Si fertilizer. X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) characterizations elucidate the principles of the calcination temperature-dependent microstructure evolution of Si fertilizers, and the akermanite Ca2Mg(Si2O7) and merwinite Ca3Mg(SiO4)2 were identified as the primary silicates products. The results of release and solubility experiments suggest the content of available metallic element and slow-release property of the Si fertilizer obtained at the optimum preparation condition (Si-OPC). The surface morphology and properties of Si-OPC were illuminated by the results of scanning electron microscope (SEM), surface area and nitrogen adsorption analysis. The acceleration action of CaCO3 in the decomposition process of talc was demonstrated by the thermogravimetry-differential scanning calorimetry (TG-DSC) test. The pot experiment corroborates that 5 g kg-1 soil Si-OPC application sufficed to facilitate the pakchoi growth by providing nutrient elements. This evidence indicates the prepared Si fertilizer as a promising candidate for Si-deficient soil replenishment.

8.
Cancer Cell Int ; 21(1): 451, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446004

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) remains one of the world's most known aggressive malignancies with a high mortality rate. Molecular biological analysis and bioinformatics are of great importance as they have recently occupied a large area in the studies related to the identification of various biomarkers to predict survival for LUAD patients. In our study, we attempted to identify a new prognostic model by developing a new algorithm to calculate the allele frequency deviation (AFD), which in turn may assist in the early diagnosis and prediction of clinical outcomes in LUAD. METHOD: First, a new algorithm was developed to calculate AFD using the whole-exome sequencing (WES) dataset. Then, AFD was measured for 102 patients, and the predictive power of AFD was assessed using Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and area under the curve (AUC). Finally, multivariable cox regression analyses were conducted to evaluate the independence of AFD as an independent prognostic tool. RESULT: The Kaplan-Meier analysis showed that AFD effectively segregated patients with LUAD into high-AFD-value and low-AFD-value risk groups (hazard ratio HR = 1.125, 95% confidence interval CI 1.001-1.26, p = 0.04) in the training group. Moreover, the overall survival (OS) of patients who belong to the high-AFD-value group was significantly shorter than that of patients who belong to the low-AFD-value group with 42.8% higher risk and 10% lower risk of death for both groups respectively (HR for death = 1.10; 95% CI 1.01-1.2, p = 0.03) in the training group. Similar results were obtained in the validation group (HR = 4.62, 95% CI 1.22-17.4, p = 0.02) with 41.6%, and 5.5% risk of death for patients who belong to the high and low-AFD-value groups respectively. Univariate and multivariable cox regression analyses demonstrated that AFD is an independent prognostic model for patients with LUAD. The AUC for 5-year survival were 0.712 and 0.86 in the training and validation groups, respectively. CONCLUSION: AFD was identified as a new independent prognostic model that could provide a prognostic tool for physicians and contribute to treatment decisions.

9.
JAMA ; 326(6): 519-530, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34374722

RESUMO

Importance: The childhood obesity rate has been steadily rising among US youths during the past 2 decades. Increasing evidence links consumption of ultraprocessed foods to excessive calorie consumption and weight gain, but trends in the consumption of ultraprocessed foods among US youths have not been well characterized. Objective: To characterize trends in the consumption of ultraprocessed foods among US youths. Design, Setting, and Participants: Serial cross-sectional analysis using 24-hour dietary recall data from a nationally representative sample of US youths aged 2-19 years (n = 33 795) from 10 cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999-2000 to 2017-2018. Exposures: Secular time. Main Outcomes and Measures: Percentage of total energy consumed from ultraprocessed foods as defined by NOVA, an established food classification system that categorizes food according to the degree of food processing. Results: Dietary intake from youths were analyzed (weighted mean age, 10.7 years; 49.1% were girls). From 1999 to 2018, the estimated percentage of total energy from consumption of ultraprocessed foods increased from 61.4% to 67.0% (difference, 5.6% [95% CI, 3.5% to 7.7%]; P < .001 for trend), whereas the percentage of total energy from consumption of unprocessed or minimally processed foods decreased from 28.8% to 23.5% (difference, -5.3% [95% CI, -7.5% to -3.2%]; P < .001 for trend). Among the subgroups of ultraprocessed foods, the estimated percentage of energy from consumption of ready-to-heat and -eat mixed dishes increased from 2.2% to 11.2% (difference, 8.9% [95% CI, 7.7% to 10.2%]) and from consumption of sweet snacks and sweets increased from 10.7% to 12.9% (difference, 2.3% [95% CI, 1.0% to 3.6%]), but the estimated percentage of energy decreased for sugar-sweetened beverages from 10.8% to 5.3% (difference, -5.5% [95% CI, -6.5% to -4.5%]) and for processed fats and oils, condiments, and sauces from 7.1% to 4.0% (difference, -3.1% [95% CI, -3.7% to -2.6%]) (all P < .05 for trend). There was a significantly larger increase in the estimated percentage of energy from consumption of ultraprocessed foods among non-Hispanic Black youths (from 62.2% to 72.5%; difference, 10.3% [95% CI, 6.8% to 13.8%]) and Mexican American youths (from 55.8% to 63.5%; difference, 7.6% [95% CI, 4.4% to 10.9%]) than the increase among non-Hispanic White youths (from 63.4% to 68.6%; difference, 5.2% [95% CI, 2.1% to 8.3%]) (P = .04 for trends). Conclusions and Relevance: Based on the NHANES cycles from 1999 to 2018, the estimated proportion of energy intake from consumption of ultraprocessed foods has increased among youths in the US and has consistently comprised the majority of their total energy intake.


Assuntos
Dieta/tendências , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Inquéritos sobre Dietas , Açúcares da Dieta , Ingestão de Energia , Fast Foods/estatística & dados numéricos , Feminino , Alimentos/classificação , Manipulação de Alimentos , Humanos , Masculino , Inquéritos Nutricionais , Lanches , Fatores Socioeconômicos , Estados Unidos , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-34247242

RESUMO

OBJECTIVE: To examine the association of long-term weight change with rheumatoid arthritis (RA) risk in a large prospective cohort study. METHODS: The Nurses' Health Study (NHS) II started in 1989 (baseline); after exclusions, we studied 108,505 women 25-42 years old without RA. Incident RA was reported by participant and confirmed by medical record review. Body weight was reported biennially through 2015. We investigated two time-varying exposures: weight changes from baseline and from age 18; change was divided into 5 categories. We used a marginal structural model (MSM) approach to account for time-varying weight change and covariates. RESULTS: Over 2,583,266 person-years, with a median follow-up time of 25.3 years, 541 women developed RA. Compared to women with stable weight from baseline, weight change was significantly associated with increased RA risk [weight gain 2-<10 kg: RR = 1.98 (95% CI 1.38, 2.85); 10-<20 kg: RR = 3.28 (95% CI 2.20, 4.89); ≥20 kg: RR = 3.81 (95% CI 2.39, 6.07); and weight loss >2 kg: RR = 2.05 (95% CI 1.28, 3.28)]. Weight gain of 10 kg or more from age 18 compared with stable weight was also associated with increased RA risk [10-< 20 kg: RR = 2.12 (95% CI 1.37, 3.27), ≥20 kg: RR = 2.31 (95% CI 1.50, 3.56)]. Consistent findings were observed for seropositive and seronegative RA. CONCLUSION: Long-term weight gain was strongly associated with increased RA risk in women, with weight gain of ≥ 20 kg associated with more than a three-fold increased RA risk. Maintenance of healthy weight may be a strategy to prevent or delay RA.

11.
Chin J Cancer Res ; 33(3): 352-363, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34321832

RESUMO

Objective: Hepatocellular carcinoma (HCC) development among hepatitis B surface antigen (HBsAg) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBsAg-positive male adults. Methods: HBsAg-positive males of 35-69 years old (N=6,153) were included from a multi-center population-based liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using B-ultrasonography and α-fetoprotein (AFP). We used logistic regression models to determine potential risk factors, built and examined the operating characteristics of a point-based algorithm for HCC risk prediction. Results: With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT (γ-glutamyl-transpeptidase), counts of platelets, white cells, concentration of DCP (des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91 (0.90-0.93), larger than existing models. At 1.5 points of risk score, 26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk, with positive prediction value of 22.85% and 12.35%, respectively. Conclusions: Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.

12.
J Natl Cancer Inst ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264325

RESUMO

BACKGROUND: Biological evidence indicates that smoking can influence macrophage functions and polarization, thereby promoting tumor evolution. We hypothesized that the association of smoking with colorectal cancer incidence might differ by macrophage infiltrates. METHODS: Utilizing the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association of smoking with incidence of colorectal cancer subclassified by macrophage counts. Multiplexed immunofluorescence [for CD68, CD86, IRF5, MAF, and MRC1 (CD206)] combined with digital image analysis and machine learning was used to identify overall, M1-polarized, and M2-polarized macrophages in tumor. We used inverse-probability-weighted multivariable Cox proportional hazards regression models to control for potential confounders and selection bias due to tissue data availability. All statistical tests were 2-sided. RESULTS: During follow-up of 131,144 participants (3,648,370 person-years), we documented 3,092 incident colorectal cancer cases including 871 cases with available macrophage data. The association of pack-years smoked with colorectal cancer incidence differed by stromal macrophage densities (Pheterogeneity=.003). Compared to never smoking, multivariable-adjusted hazard ratios (95% confidence interval) for tumors with low macrophage densities were 1.32 (0.97 to 1.79) for 1-19 pack-years, 1.31 (0.92 to 1.85) for 20-39 pack-years, and 1.74 (1.26 to 2.41) for ≥40 pack-years (Ptrend=.004). In contrast, pack-years smoked were not statistically significantly associated with the incidence of tumors having intermediate or high macrophage densities (Ptrend>.009, with the α level of 0.005). No statistically significant differential association was found for colorectal cancer subclassified by M1-like or M2-like macrophages. CONCLUSIONS: The association of smoking with colorectal cancer incidence is stronger for tumors with lower stromal macrophage counts. Our findings suggest an interplay of smoking and macrophages in colorectal carcinogenesis.

13.
Curr Microbiol ; 78(9): 3494-3504, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34279672

RESUMO

The gram-negative Pseudomonas aeruginosa is an opportunistic human pathogen that contains two different types of strains: the "classical" and the "outlier". In the "classical" strain, its bacterial subfamily I.1 lipases, such as LipA and LipC in P. aeruginosa PAO1, play critical roles in its pathogenicity. However, less is known about the subfamily I.1 lipases in the "outlier" strain, nor the evolution paths of those lipases in both types of P. aeruginosa strains. Our genome-scale investigation on I.1 lipases across different bacterial strains demonstrates the presence of one LipA-like and one new type of I.1 lipase (LipC2) in those "outlier" strains. The related genomic islands analyses further suggest that the LipC counterpart gene in the "outlier" strain was lost by gene truncation. In addition, the evolutionary analyses also indicates the horizontal LipC2 gene transfer from other gammaproteobacterial species, as well as the horizontal LipA gene transfer between two different phyla, both suggesting that the gene transfer of bacterial I.1 lipases might occur in different taxonomical levels. Our results not only provide an evidence to understand the pathogenicity among different P. aeruginosa strains, but add to the knowledge of I.1 lipase evolution in bacteria.


Assuntos
Lipase , Pseudomonas aeruginosa , Proteínas de Bactérias/genética , Transferência Genética Horizontal , Ilhas Genômicas , Humanos , Lipase/genética , Lipase/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Virulência
14.
Cancer Prev Res (Phila) ; 14(10): 945-954, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34266856

RESUMO

Prospective data are limited regarding dynamic adulthood weight changes and hepatocellular carcinoma (HCC) risk. We included 77,238 women (1980-2012) and 48,026 men (1986-2012), who recalled young-adult weight [age 18 years (women); 21 years (men)], and provided biennially updated information regarding weight, body mass index (BMI), and comorbidities. Overall adulthood weight change was defined as the difference in weight (kilograms) between young-adulthood and present. Using Cox proportional hazards models, we calculated multivariable adjusted HRs (aHR) and 95% confidence intervals (CI). Over 3,676,549 person-years, we documented 158 incident HCC cases. Elevated HCC risk was observed with higher BMI in both young-adulthood and later-adulthood [continuous aHRs per each 1 unit = 1.05; 95% CI = 1.02-1.09 (P trend = 0.019), and 1.08; 95% CI = 1.06-1.10 (P trend = 0.004), respectively]. Moreover, overall adulthood weight gain was also significantly associated with increased HCC risk (aHR per each 1-kg increase = 1.03; 95% CI = 1.01-1.08; P trend = 0.010), including after further adjusting for young-adult BMI (P trend = 0.010) and later-adult BMI (P trend = 0.008). Compared with adults with stable weight (±5 kg), the multivariable-aHRs with weight gain of 5-<10 kg, 10-<20 kg, and ≥20 kg were, 1.40 (95% CI = 0.67-2.16), 2.09 (95% CI = 1.11-3.95), and 2.61 (95% CI = 1.42-5.22), respectively. In two prospective, nationwide cohorts, adulthood weight gain was significantly associated with increased HCC risk. PREVENTION RELEVANCE: Our data suggest that maintaining a stable weight during adulthood, specifically by preventing weight gain, could represent an important public health strategy for the prevention of hepatocellular carcinoma.

15.
Cancer Epidemiol Biomarkers Prev ; 30(10): 1816-1825, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34272268

RESUMO

BACKGROUND: Patients with cancer are recommended to follow cancer prevention guidelines due to inadequate evidence for specific recommendations for cancer survivors. METHODS: We examined whether diet and lifestyle scores measuring adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention guidelines were associated with colorectal cancer-specific and overall mortality among 1,491 patients with colorectal cancer in two prospective cohorts. Cox proportional hazards regression models were used to calculate the multivariable-adjusted HRs and 95% confidence intervals (CI). RESULTS: During a median follow-up of 7.92 years, there were 641 deaths (179 colorectal cancer-specific deaths). Patients in the highest quartile of the post-diagnostic WCRF/AICR lifestyle score including diet, body mass index (BMI), and physical activity had a 24% lower risk (HR = 0.76, 95% CI: 0.49-1.18) of colorectal cancer-specific mortality and a 37% lower risk (HR = 0.63, 95% CI: 0.50-0.78) of overall mortality compared with the lowest quartile. When BMI was not included in the lifestyle score due to potential disease-related weight loss, stronger inverse associations were observed for both colorectal cancer-specific and overall mortality for the same comparison (colorectal cancer-specific: HR = 0.50, 95% CI: 0.32-0.79; overall: HR = 0.59, 95% CI: 0.47-0.75). The post-diagnostic WCRF/AICR diet score was not statistically significantly associated with either colorectal cancer-specific or overall mortality. CONCLUSIONS: Greater adherence to the WCRF/AICR cancer prevention recommendations was associated with improved survival in patients with colorectal cancer. IMPACT: This study provides support for patients with colorectal cancer to follow cancer prevention recommendations after diagnosis. Future studies on cancer survivors will continue to contribute to evidence-based diet and lifestyle recommendations for patients with cancer.

16.
Sci Rep ; 11(1): 13805, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226613

RESUMO

Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40-80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was - 0.91 standard-deviations lower in women than men (95%CI - 0.98; - 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking status point to normalization of multiple physiological processes after smoking cessation.


Assuntos
Biomarcadores/sangue , Carbono/metabolismo , Inflamação/genética , Rim/metabolismo , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Proteína C-Reativa/genética , Feminino , Humanos , Inflamação/sangue , Inflamação/metabolismo , Inflamação/patologia , Cinurenina/sangue , Masculino , Pessoa de Meia-Idade , Fumar/genética , Abandono do Hábito de Fumar , Vitaminas/sangue
17.
Hepatology ; 74(6): 3394-3408, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34216018

RESUMO

BACKGROUND AND AIMS: Most of the genetic basis of chronic liver disease remains undiscovered. APPROACH AND RESULTS: To identify genetic loci that modulate the risk of liver injury, we performed genome-wide association studies on circulating levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin across 312,671 White British participants in the UK Biobank. We focused on variants associated with elevations in all four liver biochemistries at genome-wide significance (P < 5 × 10-8 ) and that replicated using Mass General Brigham Biobank in 19,323 European ancestry individuals. We identified a genetic locus in mitochondrial glycerol-3-phosphate acyltransferase (GPAM rs10787429) associated with increased levels of ALT (P = 1.4 × 10-30 ), AST (P = 3.6 × 10-10 ), ALP (P = 9.5 × 10-30 ), and total bilirubin (P = 2.9 × 10-12 ). This common genetic variant was also associated with an allele dose-dependent risk of alcohol-associated liver disease (odd ratio [OR] = 1.34, P = 2.6 × 10-5 ) and fatty liver disease (OR = 1.18, P = 5.8 × 10-4 ) by International Classification of Diseases, 10th Revision codes. We identified significant interactions between GPAM rs10787429 and elevated body mass index in association with ALT and AST (P = 7.1 × 10-9 and 3.95 × 10-8 , respectively), as well as between GPAM rs10787429 and weekly alcohol consumption in association with ALT, AST, and alcohol-associated liver disease (P = 4.0 × 10-2 , 1.6 × 10-2 , and 1.3 × 10-2 , respectively). Unlike previously described genetic variants that are associated with an increased risk of liver injury but confer a protective effect on circulating lipids, GPAM rs10787429 was associated with an increase in total cholesterol (P = 2.0 × 10-17 ), LDL cholesterol (P = 2.0 × 10-10 ), and HDL cholesterol (P = 6.6 × 10-37 ). Single-cell RNA-sequencing data demonstrated hepatocyte-predominant expression of GPAM in cells that co-express genes related to VLDL production (P = 9.4 × 10-103 ). CONCLUSIONS: Genetic variation in GPAM is associated with susceptibility to liver injury. GPAM may represent a therapeutic target in chronic liver disease.

18.
ACS Appl Mater Interfaces ; 13(24): 29130-29136, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34126739

RESUMO

The natural-product-based low-molecular-weight supramolecular hydrogels (LMWSHs) induced by heating are rarely reported. In this work, a simple salt of oleanolic acid (OA) and choline ([choline][OA]) was used as the natural product hydrogelator (NPHG) to form LMWSHs. Unlike common sol-gel transitions, the OA-based LMWSH displayed a unique property with which the system could undergo a phase transition from the sol state to the gel state upon heating. Moreover, the phase separation was observed in sol and gel states when the temperature was elevated with nonreversible transparent-turbid transitions. LMWSHs showed good stability and injectability and the potential to be a drug delivery vehicle for sustained release of drugs. In this regard, this work provided a facile approach to designing an OA-based NPHG for preparing heat-induced LMWSHs.

19.
Cancer Cell Int ; 21(1): 294, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34092242

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common types in the world with a high mortality rate. Despite advances in treatment strategies, the overall survival (OS) remains short. Our study aims to establish a reliable prognostic signature closely related to the survival of LUAD patients that can better predict prognosis and possibly help with individual monitoring of LUAD patients. METHODS: Raw RNA-sequencing data were obtained from Fudan University and used as a training group. Differentially expressed genes (DEGs) for the training group were screened. The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate cox regression analysis were conducted to identify the candidate prognostic genes and construct the risk score model. Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC) curve were used to evaluate the prognostic power and performance of the signature. Moreover, The Cancer Genome Atlas (TCGA-LUAD) dataset was further used to validate the predictive ability of prognostic signature. RESULTS: A prognostic signature consisting of seven prognostic-related genes was constructed using the training group. The 7-gene prognostic signature significantly grouped patients in high and low-risk groups in terms of overall survival in the training cohort [hazard ratio, HR = 8.94, 95% confidence interval (95% CI)] [2.041-39.2]; P = 0.0004), and in the validation cohort (HR = 2.41, 95% CI [1.779-3.276]; P < 0.0001). Cox regression analysis (univariate and multivariate) demonstrated that the seven-gene signature is an independent prognostic biomarker for predicting the survival of LUAD patients. ROC curves revealed that the 7-gene prognostic signature achieved a good performance in training and validation groups (AUC = 0.91, AUC = 0.7 respectively) in predicting OS for LUAD patients. Furthermore, the stratified analysis of the signature showed another classification to predict the prognosis. CONCLUSION: Our study suggested a new and reliable prognostic signature that has a significant implication in predicting overall survival for LUAD patients and may help with early diagnosis and making effective clinical decisions regarding potential individual treatment.

20.
Cancer Discov ; 11(10): 2446-2455, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34140290

RESUMO

Several risk factors have been established for colorectal cancer, yet their direct mutagenic effects in patients' tumors remain to be elucidated. Here, we leveraged whole-exome sequencing data from 900 colorectal cancer cases that had occurred in three U.S.-wide prospective studies with extensive dietary and lifestyle information. We found an alkylating signature that was previously undescribed in colorectal cancer and then showed the existence of a similar mutational process in normal colonic crypts. This alkylating signature is associated with high intakes of processed and unprocessed red meat prior to diagnosis. In addition, this signature was more abundant in the distal colorectum, predicted to target cancer driver mutations KRAS p.G12D, KRAS p.G13D, and PIK3CA p.E545K, and associated with poor survival. Together, these results link for the first time a colorectal mutational signature to a component of diet and further implicate the role of red meat in colorectal cancer initiation and progression. SIGNIFICANCE: Colorectal cancer has several lifestyle risk factors, but the underlying mutations for most have not been observed directly in tumors. Analysis of 900 colorectal cancers with whole-exome sequencing and epidemiologic annotations revealed an alkylating mutational signature that was associated with red meat consumption and distal tumor location, as well as predicted to target KRAS p.G12D/p.G13D.This article is highlighted in the In This Issue feature, p. 2355.

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