ResearchPad - original-research-communications https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Vitamin D, magnesium, calcium, and their interaction in relation to colorectal cancer recurrence and all-cause mortality]]> https://www.researchpad.co/article/elastic_article_12388 Higher concentrations of 25-hydroxyvitamin D3 [25(OH)D3] at diagnosis are associated with a lower mortality risk in colorectal cancer (CRC) patients. However, magnesium and calcium are important in vitamin D metabolism.ObjectivesWe aimed to investigate 25(OH)D3, magnesium, or calcium and their interaction among patients with CRC in relation to recurrence and all-cause mortality.MethodsThe study population included 1169 newly diagnosed stage I–III CRC patients from 2 prospective cohorts. Associations between 25(OH)D3 concentrations, magnesium or calcium intake through diet and/or supplements at diagnosis, and recurrence and all-cause mortality were evaluated using multivariable Cox proportional hazard models. The interaction between 25(OH)D3 and magnesium or calcium was assessed by investigating 1) joint compared with separate effects, using a single reference category; and 2) the effect estimates of 1 factor across strata of another.ResultsSerum 25(OH)D3, calcium, and magnesium, alone and their interactions, were not associated with recurrence. Serum 25(OH)D3 concentrations seemed to be associated with all-cause mortality. An inverse association between magnesium intake (HRQ3 vs. Q1: 0.55; 95% CI: 0.32, 0.95 and HRQ4 vs. Q1: 0.65; 95% CI: 0.35, 1.21), but not calcium intake, and all-cause mortality was observed. When investigating the interaction between 25(OH)D3 and magnesium, we observed the lowest risk of all-cause mortality in patients with sufficient vitamin D concentrations (≥50 nmol/L) and a high magnesium intake (median split) (HR: 0.53; 95% CI: 0.31, 0.89) compared with patients who were vitamin D deficient (<50 nmol/L) and had a low magnesium intake. No interactions between calcium and vitamin D in relation to all-cause mortality were observed.ConclusionsOur findings suggest that the presence of an adequate status of 25(OH)D3 in combination with an adequate magnesium intake is essential in lowering the risk of mortality in CRC patients, yet the underlying mechanism should be studied. In addition, diet and lifestyle intervention studies are needed to confirm our findings. The COLON study was registered at clinicaltrials.gov as NCT03191110. The EnCoRe study was registered at trialregister.nl as NTR7099. ]]> <![CDATA[Could vitamin D reduce obesity-associated inflammation? Observational and Mendelian randomization study]]> https://www.researchpad.co/article/elastic_article_12372 Obesity is associated with inflammation but the role of vitamin D in this process is not clear.ObjectivesWe aimed to assess the associations between serum 25-hydroxyvitamin D [25(OH)D], BMI, and 16 inflammatory biomarkers, and to assess the role of vitamin D as a potential mediator in the association between higher BMI and inflammation.MethodsNorthern Finland Birth Cohort 1966 (NFBC1966) 31-y data on 3586 individuals were analyzed to examine the observational associations between BMI, 25(OH)D, and 16 inflammatory biomarkers. Multivariable regression analyses and 2-sample regression-based Mendelian randomization (MR) mediation analysis were performed to assess any role of vitamin D in mediating a causal effect of BMI on inflammatory biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and α1-acid glycoprotein (AGP)] for which observational associations were detected. For MR, genome-wide association study summary results ranging from 5163 to 806,834 individuals were used for biomarkers, 25(OH)D, and BMI. Findings were triangulated with a literature review of vitamin D supplementation trials.ResultsIn NFBC1966, mean BMI (kg/m2) was 24.8 (95% CI: 24.7, 25.0) and mean 25(OH)D was 50.3 nmol/L (95% CI: 49.8, 50.7 nmol/L). Inflammatory biomarkers correlated as 4 independent clusters: interleukins, adhesion molecules, acute-phase proteins, and chemokines. BMI was positively associated with 9 inflammatory biomarkers and inversely with 25(OH)D (false discovery rate < 0.05). 25(OH)D was inversely associated with sICAM-1, hs-CRP, and AGP, which were positively associated with BMI. The MR analyses showed causal association of BMI on these 3 inflammatory biomarkers. There was no observational or MR evidence that circulating 25(OH)D concentrations mediated the association between BMI and these 3 inflammatory markers. Review of randomized controlled trials (RCTs) supported our findings showing no impact of vitamin D supplementation on inflammatory biomarkers.ConclusionsThe findings from our observational study and causal MR analyses, together with data from RCTs, do not support a beneficial role of vitamin D supplementation on obesity-related inflammation. ]]> <![CDATA[Effects of distraction on taste-related neural processing: a cross-sectional fMRI study]]> https://www.researchpad.co/article/elastic_article_12368 In the current obesogenic environment we often eat while electronic devices, such as smart phones, computers, or the television, distract us. Such “distracted eating” is associated with increased food intake and overweight. However, the underlying neurocognitive mechanisms of this phenomenon are unknown.ObjectiveOur aim was to elucidate these mechanisms by investigating whether distraction attenuates processing in the primary and secondary taste cortices, located in the insula and orbitofrontal cortex (OFC), respectively.MethodsForty-one healthy, normal-weight participants received fixed amounts of higher- and lower-sweetness isocaloric chocolate milk while performing a high- or low-distracting detection task during fMRI in 2 test sessions. Subsequently, we measured ad libitum food intake.ResultsAs expected, a primary taste cortex region in the right insula responded more to the sweeter drink (P < 0.001, uncorrected). Distraction did not affect this insular sweetness response across the group, but did weaken sweetness-related connectivity of this region to a secondary taste region in the right OFC (P–family-wise error, cluster, small-volume corrected = 0.020). Moreover, individual differences in distraction-related attenuation of taste activation in the insula predicted increased subsequent ad libitum food intake after distraction (= 0.36).ConclusionsThese results reveal a mechanism explaining how distraction during consumption attenuates neural taste processing. Moreover, our study shows that such distraction-induced decreases in neural taste processing contribute to individual differences in the susceptibility for overeating. Thus, being mindful about the taste of food during consumption could perhaps be part of successful prevention and treatment of overweight and obesity, which should be further tested in these target groups. This study was preregistered at the Open Science Framework as https://bit.ly/31RtDHZ. ]]> <![CDATA[The associations of longitudinal changes in consumption of total and types of dairy products and markers of metabolic risk and adiposity: findings from the European Investigation into Cancer and Nutrition (EPIC)–Norfolk study, United Kingdom]]> https://www.researchpad.co/article/Nc5cc96cc-4861-4bbe-9e48-1cbfff4c23a8 The consumption of some types of dairy products has been associated with lower cardiometabolic disease incidence. Knowledge remains limited about habitual dairy consumption and the pathways to cardiometabolic risk.ObjectiveWe aimed to investigate associations of habitual consumption of total and types of dairy products with markers of metabolic risk and adiposity among adults in the United Kingdom.MethodsWe examined associations of changes in dairy consumption (assessed with a food-frequency questionnaire) with parallel changes in cardiometabolic markers using multiple linear regression among 15,612 adults aged 40–78 y at baseline (1993–1997) and followed up over 1998–2000 (mean ± SD: 3.7±0.7 y) in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk study.ResultsFor adiposity, an increase in fermented dairy products [yogurt (total or low-fat) or low-fat cheese] consumption was associated with a lower increase in body weight and body mass index (BMI). For example, over 3.7 y, increasing yogurt consumption by 1 serving/d was associated with a smaller increase in body weight by 0.23 kg (95% CI: −0.46, −0.01 kg). An increase in full-fat milk, high-fat cheese, and total high-fat dairy was associated with greater increases in body weight and BMI [e.g., for high-fat dairy: β = 0.13 (0.05, 0.21) kg and 0.04 (0.01, 0.07) kg/m2, respectively]. For lipids, an increase in milk (total and low-fat) or yogurt consumption was positively associated with HDL cholesterol. An increase in total low-fat dairy was negatively associated with LDL cholesterol (−0.03 mmol/L; −0.05, −0.01 mmol/L), whereas high-fat dairy (total, butter, and high-fat cheese) consumption was positively associated [e.g., 0.04 (0.02, 0.06) mmol/L for total high-fat dairy]. For glycemia, increasing full-fat milk consumption was associated with a higher increase in glycated hemoglobin (P = 0.027).ConclusionsThe habitual consumption of different dairy subtypes may differently influence cardiometabolic risk through adiposity and lipid pathways. ]]> <![CDATA[Enteral delivery of proteins enhances the expression of proteins involved in the cytoskeleton and protein biosynthesis in human duodenal mucosa]]> https://www.researchpad.co/article/N5b0e54ba-e259-4c56-8b8c-bcf3d2b81bc7

ABSTRACT

Background: Amino acids are well known to be key effectors of gut protein turnover. We recently reported that enteral delivery of proteins markedly stimulated global duodenal protein synthesis in carbohydrate-fed healthy humans, but specifically affected proteins remain unknown.

Objective: We aimed to assess the influence of an enteral protein supply on the duodenal mucosal proteome in carbohydrate-fed humans.

Design: Six healthy volunteers received for 5 h, on 2 occasions and in random order, either an enteral infusion of maltodextrins alone (0.25 g · kg−1 · h−1) mimicking the fed state or maltodextrins with a protein powder (0.14 g proteins · kg−1 · h−1). Endoscopic duodenal biopsy specimens were then collected and frozen until analysis. A 2-dimensional polyacrylamide gel electrophoresis–based comparative proteomics analysis was then performed, and differentially expressed proteins (at least ±1.5-fold change; Student’s t test, P < 0.05) were identified by mass spectrometry. Protein expression changes were confirmed by Western blot analysis.

Results: Thirty-two protein spots were differentially expressed after protein delivery compared with maltodextrins alone: 28 and 4 spots were up- or downregulated, respectively. Among the 22 identified proteins, 11 upregulated proteins were involved either in the cytoskeleton (ezrin, moesin, plastin 1, lamin B1, vimentin, and β-actin) or in protein biosynthesis (glutamyl-prolyl–transfer RNA synthetase, glutaminyl–transfer RNA synthetase, elongation factor 2, elongation factor 1δ, and eukaryotic translation and initiation factor 3 subunit f).

Conclusions: Enteral delivery of proteins altered the duodenal mucosal proteome and mainly stimulated the expression of proteins involved in cytoskeleton and protein biosynthesis. These results suggest that protein supply may affect intestinal morphology by stimulating actin cytoskeleton remodeling. This trial was registered at clinicaltrials.gov as NCT01254110.

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<![CDATA[Genetic risk, adherence to a healthy lifestyle, and type 2 diabetes risk among 550,000 Chinese adults: results from 2 independent Asian cohorts]]> https://www.researchpad.co/article/N31cc027b-fa3c-481b-acd0-f50f4c841a4e

ABSTRACT

Background

Whether genetic susceptibility to type 2 diabetes is modified by a healthy lifestyle among Chinese remains unknown.

Objectives

The aim of the study was to determine whether genetic risk and adherence to a healthy lifestyle contribute independently to the risk of developing type 2 diabetes.

Methods

We defined a lifestyle score using BMI, alcohol intake, smoking, physical activities, and diets in 461,030 participants from the China Kadoorie Biobank and 38,434 participants from the Singapore Chinese Health Study. A genetic risk score was constructed based on type 2 diabetes loci among 100,175 and 16,172 participants in each cohort, respectively. A Cox proportional-hazards model was used to estimate the interaction between genetic and lifestyle factors on the risk of type 2 diabetes.

Results

In 2 independent Asian cohorts, we consistently found a healthy lifestyle (the bottom quintile of lifestyle score) was associated with a substantially lower risk of type 2 diabetes than an unhealthy lifestyle (the top quintile of lifestyle score) regardless of genetic risk. In those at a high genetic risk, the risk of type 2 diabetes was 57% lower among participants with a healthy lifestyle than among those with an unhealthy lifestyle in the pooled cohorts. Among participants at high genetic risk, the standardized 10-y incidence of type 2 diabetes was 7.11% in those with an unhealthy lifestyle vs. 2.45% in those with a healthy lifestyle.

Conclusions

In 2 independent cohorts involving 558,302 Chinese participants, we did not observe an interaction between genetics and lifestyle with type 2 diabetes risk, but our findings provide replicable evidence to show lifestyle factors and genetic factors were independently associated with the risk of type 2 diabetes. Within any genetic risk category, a healthy lifestyle was associated with a significantly lower risk of type 2 diabetes among the Chinese population.

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<![CDATA[Evidence of gut enteropathy and factors associated with undernutrition among slum-dwelling adults in Bangladesh]]> https://www.researchpad.co/article/N06ff69e2-c801-4500-bccc-1f72c91e7cd2

ABSTRACT

Background

Adult undernutrition (BMI <18.5 kg/m2) is responsible for immune deficits, increased risk of disease burden, and higher rates of mortality. The prevalence of adult undernutrition in Bangladesh is substantial, but there have been few studies on the etiology of this condition for the inhabitants of urban slums.

Objective

The aim of this study was to identify the factors associated with undernutrition among slum-dwelling adults in Bangladesh.

Methods

A case-control study was conducted in the Bauniabadh area of Dhaka, Bangladesh. 270 adult participants (135 cases with a BMI <18.5 and 135 controls with a BMI between 18.5 and 24.9) aged 18–45 y were enrolled between October 2018 and January 2019. Sociodemographic variables, dietary diversity, micronutrient deficiencies, psychological symptoms, infection, and biomarkers of gut health were assessed to identify the factors associated with undernutrition using multivariable logistic regression analysis.

Results

A higher number of siblings [adjusted odds ratio (aOR): 1.39; 95% CI: 1.11, 1.77], increased self-reporting questionnaire-20 score (an instrument to screen mental health disorders and detect psychological symptoms) (aOR: 1.12; 95% CI: 1.04, 1.23), elevated fecal concentration of α-1 antitrypsin (aOR: 4.82; 95% CI: 1.01, 25.29), and anemia (aOR: 3.63; 95% CI: 1.62, 8.58) were positively associated with undernutrition in adults. Age (aOR: 0.90; 95% CI: 0.84, 0.96), dietary diversity score (aOR: 0.75; 95% CI: 0.56, 0.99), C-reactive protein (aOR: 0.82; 95% CI: 0.73, 0.92), Helicobacter pylori infection (aOR: 0.11; 95% CI: 0.05, 0.23), and always washing hands before eating or preparing foods (aOR: 0.33; 95% CI: 0.12, 0.87) were associated with reduced odds of undernutrition among the study population.

Conclusions

Our results indicate that undernutrition in slum-dwelling adults in Bangladesh is associated with numerous physiological and sociodemographic factors, including evidence of gastrointestinal inflammation and altered intestinal permeability.

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<![CDATA[Trajectory of body mass and skeletal muscle indices and disease progression in metastatic colorectal cancer patients]]> https://www.researchpad.co/article/N7ae2c34a-bd5a-4b63-b8c3-c2deaa048b63

ABSTRACT

Background

Knowledge of the evolution of BMI and skeletal muscle index (SMI) measurements during advanced cancer and their relationships with disease progression (PD) is relevant to improve the timing of interventions that may improve cachexia-associated outcomes.

Objectives

We investigated BMI and SMI trajectories and their associations with PD in metastatic colorectal cancer (mCRC) patients during consecutive palliative systemic regimens.

Methods

In a secondary analysis of the primary CAIRO3 trial, we included 533 mCRC patients with BMI measurements repeated every 3 wk and 95 randomly selected patients with SMI measurements repeated every 9 wk. We studied 2 periods: p1, during first-line maintenance capecitabine + bevacizumab or observation until the first progression of disease (PD1); and p2, during capecitabine + oxaliplatin + bevacizumab or another reintroduction treatment from PD1 until the second progression of disease (PD2). BMI and SMI trajectories were modeled separately throughout both periods, and joint longitudinal-survival modeling was used to investigate the relationships between slopes in BMI and SMI with PD at 9 and 3 wk pre-PD. A multivariate longitudinal joint model was used to investigate the association between the BMI trajectory and PD at time of PD, independent of SMI.

Results

During p1, the slopes in BMI and SMI were associated with early PD1 [HRs for 9-wk BMI: 1.54 (95% CI: 1.33, 1.76); 9-wk SMI: 1.38 (95% CI: 0.87, 1.89), NS; 3-wk BMI: 1.74 (95% CI: 1.48, 1.99); 3-wk SMI: 2.65 (95% CI: 1.97, 3.32)]. During p2, only the slope in SMI was related to PD2 [9-wk BMI: 1.09 (95%: CI: 0.73, 1.45), NS; 9-wk SMI: 1.64 (95% CI: 1.25, 2.04); 3-wk BMI: 1.17 (95% CI: 0.77, 1.57); 3-wk SMI: 1.11 (95% CI: 0.70, 1.53)]. In models mutually adjusting for BMI and SMI, SMI was associated with PD in p1 [p1 ( n = 95), HR BMI: 1.32 (95% CI: 0.74, 2.39), NS; p1, HR SMI: 1.50 (95% CI: 1.04, 2.14); p2 ( n = 50), BMI: 0.98 (95% CI: 0.55, 1.75), NS; p2, HR SMI: 1.11 (95% CI: 0.61, 2.05), NS].

Conclusions

In mCRC patients during palliative systemic treatment, SMI losses, irrespective of BMI losses, may be a marker for the early initiation of cachexia interventions.

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<![CDATA[Brown adipose tissue volume and 18F-fluorodeoxyglucose uptake are not associated with energy intake in young human adults]]> https://www.researchpad.co/article/N53e83287-4fde-4d0d-bdd7-fbc756f37c03

ABSTRACT

Background

Several studies have explored the role of human brown adipose tissue (BAT) in energy expenditure. However, the link between BAT and appetite regulation needs to be more rigorously examined.

Objectives

We aimed to investigate the associations of BAT volume and 18F-fluordeoxyglucose (18F-FDG) uptake after a personalized cold exposure with energy intake and appetite-related sensations in young healthy humans.

Methods

A total of 102 young adults (65 women; age: 22.08 ± 2.17 y; BMI: 25.05 ± 4.93 kg/m 2) took part in this cross-sectional study. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18F-FDG uptake were assessed by means of static 18F-FDG positron-emission tomography and computed tomography scans after a 2-h personalized exposure to cold. Energy intake was estimated via an objectively measured ad libitum meal and three nonconsecutive 24-h dietary recalls. Appetite-related sensations (i.e., hunger and fullness) were recorded by visual analog scales before and after a standardized breakfast (energy content = 50% of basal metabolic rate) and the ad libitum meal. Body composition was assessed by a whole-body DXA scan.

Results

BAT volume and 18F-FDG uptake were not associated with quantified ad libitum energy intake (all P > 0.088), nor with habitual energy intake estimated from the 24-h dietary recalls (all P  > 0.683). Lean mass was positively associated with both the energy intake from the ad libitum meal (β: 17.612, R2 = 0.213; P < 0.001) and the habitual energy intake (β: 16.052, R2 = 0.123; P = 0.001). Neither the interaction BAT volume × time elapsed after meal consumption nor that of BAT 18F-FDG uptake × time elapsed after meal consumption had any significant influence on appetite-related sensations after breakfast or after meal consumption (all P > 0.3).

Conclusions

Neither BAT volume, nor BAT 18F-FDG uptake after cold stimulation, are related to appetite regulation in young adults. These results suggest BAT plays no important role in the regulation of energy intake in humans.

This trial was registered at clinicaltrials.gov as NCT02365129.

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<![CDATA[The role of the gut microbiome in the association between habitual anthocyanin intake and visceral abdominal fat in population-level analysis]]> https://www.researchpad.co/article/N794a55f9-27e8-4e85-8d31-2427bb10621a

ABSTRACT

Background

Flavonoid intake modifies the composition of the gut microbiome, which contributes to the metabolism of flavonoids. Few studies have examined the contribution of the gut microbiome to the health benefits associated with flavonoid intake.

Objectives

We aimed to examine associations between habitual intakes of flavonoid subclasses and MRI-determined visceral (VAT) and subcutaneous (SAT) adipose tissue. Uniquely, we also identified associations between the aforementioned measurements and gut microbiome composition sequenced from 16S ribosomal RNA genes.

Methods

We undertook cross-sectional analyses of 618 men and women (n = 368 male), aged 25–83 y, from the PopGen cohort.

Results

Higher intake of anthocyanins was associated with lower amounts of VAT [tertile (T)3-T1:  −0.49 dm3; β: −8.9%; 95% CI: −16.2%, −1.1%; = 0.03] and VAT:SAT ratio (T3-T1: −0.04; β: −7.1%; 95% CI: −13.5%, −0.3%; = 0.03). Higher intakes of anthocyanin-rich foods were also inversely associated with VAT [quantile (Q)4-Q1: −0.39 dm3; β: −9.9%; 95% CI: −17.4%, −1.6%; = 0.02] and VAT:SAT ratio (Q4-Q1: −0.04; β: −6.5%; 95% CI: −13.3%, −0.9%; = 0.03). Participants with the highest intakes of anthocyanin-rich foods also had higher microbial diversity (Q4-Q1: β: 0.18; 95% CI: 0.06, 0.31; P < 0.01), higher abundances of Clostridiales (Q4-Q1: β: 449; 95% CI: 96.3, 801; = 0.04) and Ruminococcaceae (Q4-Q1: β: 313; 95% CI: 33.6, 591; = 0.04), and lower abundance of Clostridium XIVa (Q4-Q1: β: −41.1; 95% CI: −72.4, −9.8; = 0.04). Participants with the highest microbial diversity, abundances of Clostridiales and Ruminococcaceae, and lower abundance of Clostridium XIVa had lower amounts of VAT. Up to 18.5% of the association between intake of anthocyanin-rich foods and VAT could be explained by the gut microbiome.

Conclusions

These novel data suggest that higher microbial diversity and abundance of specific taxa in the Clostridiales order may contribute to the association between higher intake of anthocyanins and lower abdominal adipose tissue.

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<![CDATA[Two apples a day lower serum cholesterol and improve cardiometabolic biomarkers in mildly hypercholesterolemic adults: a randomized, controlled, crossover trial]]> https://www.researchpad.co/article/Ne6879576-4e05-438c-a24c-49734dc1393b

ABSTRACT

BACKGROUND

Apples are rich in bioactive polyphenols and fiber. Evidence suggests that consumption of apples or their bioactive components is associated with beneficial effects on lipid metabolism and other markers of cardiovascular disease (CVD). However, adequately powered randomized controlled trials are necessary to confirm these data and explore the mechanisms.

OBJECTIVE

We aimed to determine the effects of apple consumption on circulating lipids, vascular function, and other CVD risk markers.

METHODS

The trial was a randomized, controlled, crossover, intervention study. Healthy mildly hypercholesterolemic volunteers (23 women, 17 men), with a mean ± SD BMI 25.3 ± 3.7 kg/m2 and age 51 ± 11 y, consumed 2 apples/d [Renetta Canada, rich in proanthocyanidins (PAs)] or a sugar- and energy-matched apple control beverage (CB) for 8 wk each, separated by a 4-wk washout period. Fasted blood was collected before and after each treatment. Serum lipids, glucose, insulin, bile acids, and endothelial and inflammation biomarkers were measured, in addition to microvascular reactivity, using laser Doppler imaging with iontophoresis, and arterial stiffness, using pulse wave analysis.

RESULTS

Whole apple (WA) consumption decreased serum total (WA: 5.89 mmol/L; CB: 6.11 mmol/L; P = 0.006) and LDL cholesterol (WA: 3.72 mmol/L; CB: 3.86 mmol/L; P = 0.031), triacylglycerol (WA: 1.17 mmol/L; CB: 1.30 mmol/L; P = 0.021), and intercellular cell adhesion molecule-1 (WA: 153.9 ng/mL; CB: 159.4 ng/mL; P = 0.028), and increased serum uric acid (WA: 341.4 μmol/L; CB: 330 μmol/L; P = 0.020) compared with the CB. The response to endothelium-dependent microvascular vasodilation was greater after the apples [WA: 853 perfusion units (PU), CB: 760 PU; P = 0.037] than after the CB. Apples had no effect on blood pressure or other CVD markers.

Conclusions

These data support beneficial hypocholesterolemic and vascular effects of the daily consumption of PA-rich apples by mildly hypercholesterolemic individuals.

This trial was registered at clinicaltrials.gov as NCT01988389.

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<![CDATA[The association of fish consumption and its urinary metabolites with cardiovascular risk factors: the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP)]]> https://www.researchpad.co/article/N46311f01-d886-404b-8e11-d1d8ba11d7c8

ABSTRACT

Background

Results from observational studies regarding associations between fish (including shellfish) intake and cardiovascular disease risk factors, including blood pressure (BP) and BMI, are inconsistent.

Objective

To investigate associations of fish consumption and associated urinary metabolites with BP and BMI in free-living populations.

Methods

We used cross-sectional data from the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP), including 4680 men and women (40–59 y) from Japan, China, the United Kingdom, and United States. Dietary intakes were assessed by four 24-h dietary recalls and BP from 8 measurements. Urinary metabolites (2 timed 24-h urinary samples) associated with fish intake acquired from NMR spectroscopy were identified. Linear models were used to estimate BP and BMI differences across categories of intake and per 2 SD higher intake of fish and its biomarkers.

Results

No significant associations were observed between fish intake and BP. There was a direct association with fish intake and BMI in the Japanese population sample (P trend = 0.03; fully adjusted model). In Japan, trimethylamine-N-oxide (TMAO) and taurine, respectively, demonstrated area under the receiver operating characteristic curve (AUC) values of 0.81 and 0.78 in discriminating high against low fish intake, whereas homarine (a metabolite found in shellfish muscle) demonstrated an AUC of 0.80 for high/nonshellfish intake. Direct associations were observed between urinary TMAO and BMI for all regions except Japan (P < 0.0001) and in Western populations between TMAO and BP (diastolic blood pressure: mean difference 1.28; 95% CI: 0.55, 2.02 mmHg; P = 0.0006, systolic blood pressure: mean difference 1.67; 95% CI: 0.60, 2.73 mmHg; P = 0.002).

Conclusions

Urinary TMAO showed a stronger association with fish intake in the Japanese compared with the Western population sample. Urinary TMAO was directly associated with BP in the Western but not the Japanese population sample. Associations between fish intake and its biomarkers and downstream associations with BP/BMI appear to be context specific. INTERMAP is registered at www.clinicaltrials.gov as NCT00005271.

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<![CDATA[Intake of vitamin D and calcium, sun exposure, and risk of breast cancer subtypes among black women]]> https://www.researchpad.co/article/N445047c2-70c8-49c4-bc93-5116669e08e7

ABSTRACT

Background

The randomized placebo-controlled Vitamin D and Omega-3 Trial suggested a possible benefit of vitamin D on cancer incidence among black individuals. However, data are limited regarding the impact of vitamin D on breast cancer subtypes among African-American/black women, who tend to develop more aggressive forms of breast cancer.

Objectives

We hypothesize that more vitamin D exposure (through diet, supplements, and sunlight) and higher intake of calcium are associated with decreased risk of estrogen receptor (ER)+ and ER− breast cancer, and of triple-negative breast cancer (TNBC) among black women.

Methods

This study was conducted among 1724 black cases and 1233 controls in the Women's Circle of Health Study (WCHS) and WCHS2. Polytomous logistic regressions were used to estimate ORs and 95% CIs of ER+ and ER− breast cancer; logistic regressions were used for TNBC. The ORs from each study were pooled using an inverse-variance-weighted random-effects model.

Results

Dietary vitamin D and calcium intake were not associated with risk of breast cancer subtypes in the pooled analysis. For supplemental vitamin D, we observed possible inverse associations between intake of ≤800 IU/d (compared with nonuse) and risk of several subtypes, with effects that appeared strongest for TNBC (OR: 0.58; 95% CI: 0.35, 0.94); no association was found for >800 IU/d. More daylight hours spent outdoors in a year was associated with lower risk of ER+, ER−, and TNBC (e.g., highest compared with lowest quartile: TNBC OR: 0.53; 95% CI: 0.31, 0.91; P-trend = 0.02).

Conclusions

Moderate supplemental vitamin D intake was associated with decreased risk of TNBC, and increased sun exposure was associated with reduced risk of ER+, ER−, and TNBC among black women.

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<![CDATA[Scavenging Reactive Oxygen Species Production Normalizes Ferroportin Expression and Ameliorates Cellular and Systemic Iron Disbalances in Hemolytic Mouse Model]]> https://www.researchpad.co/article/5c0aedd6d5eed0c48459d247

Abstract

Aims: Release of large amounts of free heme into circulation, overproduction of reactive oxygen species (ROS), and activation of toll-like receptor-4-dependent responses are considered critical for the ability of heme to promote oxidative stress and to initiate proinflammatory responses, posing a serious threat to the body. A deep understanding of the consequences of heme overload on the regulation of cellular and systemic iron homeostasis is, however, still lacking.

Results: The effects of heme on iron metabolism were studied in primary macrophages and in mouse models of acute and chronic hemolysis. We demonstrated that hemolysis was associated with a significant depletion of intracellular iron levels and increased expression of the sole iron exporter protein, ferroportin. The pathophysiological relevance of this mechanism was further demonstrated in sickle cell anemia mice, which, despite chronic hemolysis, maintained high ferroportin expression and increased iron export. We identified a redox active iron species and superoxide as regulators for ferroportin induction by heme. Scavenging the ROS production, by use of a pharmacological antioxidant N-acetylcysteine, prevented ferroportin induction and normalized intracellular iron levels in macrophages and in experimentally induced hemolysis in mice.

Innovation: Our data propose that scavenging ROS levels may be a novel therapeutic strategy to balance intracellular iron levels and systemic iron influx in conditions associated with heme overload.

Conclusion: This study identifies that the pro-oxidant, and not the proinflammatory, actions of heme profoundly impact on iron homeostasis by critically regulating the expression of ferroportin and iron export in hemolytic conditions. Antioxid. Redox Signal. 29, 484–499.

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<![CDATA[The Broad-Spectrum Antimicrobial Potential of [Mn(CO)4(S2CNMe(CH2CO2H))], a Water-Soluble CO-Releasing Molecule (CORM-401): Intracellular Accumulation, Transcriptomic and Statistical Analyses, and Membrane Polarization]]> https://www.researchpad.co/article/5bff41d4d5eed0c484aa1e2a

Abstract

Aims: Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM.

Results: [Mn(CO)4S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. CORM-401 releases CO that binds oxidases in vivo, but is an ineffective respiratory inhibitor. Extensive CORM accumulation (assayed as intracellular manganese) accompanies antimicrobial activity. CORM-401 stimulates respiration, polarizes the cytoplasmic membrane in an uncoupler-like manner, and elicits loss of intracellular potassium and zinc. Transcriptomics and mathematical modeling of transcription factor activities reveal a multifaceted response characterized by elevated expression of genes encoding potassium uptake, efflux pumps, and envelope stress responses. Regulators implicated in stress responses (CpxR), respiration (Arc, Fnr), methionine biosynthesis (MetJ), and iron homeostasis (Fur) are significantly disturbed. Although CORM-401 reduces bacterial growth in combination with cefotaxime and trimethoprim, fractional inhibition studies reveal no interaction.

Innovation: We present the most detailed microbiological analysis yet of a CORM that is not a ruthenium carbonyl. We demonstrate CO-independent striking effects on the bacterial membrane and global transcriptomic responses.

Conclusions: CORM-401, contrary to our expectations of a CO delivery vehicle, does not inhibit respiration. It accumulates in the cytoplasm, acts like an uncoupler in disrupting cytoplasmic ion balance, and triggers multiple effects, including osmotic stress and futile respiration.

Rebound Track: This work was rejected during standard peer review and rescued by rebound peer review (Antioxid Redox Signal 16: 293–296, 2012) with the following serving as open reviewers: Miguel Aon, Giancarlo Biagini, James Imlay, and Nigel Robinson. Antioxid. Redox Signal. 28, 1286–1308.

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