Plant-based diets are recommended for coronary heart disease (CHD) prevention. However, not all plant foods are necessarily beneficial for health.
This study sought to examine associations between ...plant-based diet indices and CHD incidence.
We included 73,710 women in NHS (Nurses’ Health Study) (1984 to 2012), 92,329 women in NHS2 (1991 to 2013), and 43,259 men in Health Professionals Follow-up Study (1986 to 2012), free of chronic diseases at baseline. We created an overall plant-based diet index (PDI) from repeated semiquantitative food-frequency questionnaire data, by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful plant-based diet index (hPDI) where healthy plant foods (whole grains, fruits/vegetables, nuts/legumes, oils, tea/coffee) received positive scores, whereas less-healthy plant foods (juices/sweetened beverages, refined grains, potatoes/fries, sweets) and animal foods received reverse scores. To create an unhealthful PDI (uPDI), we gave positive scores to less-healthy plant foods and reverse scores to animal and healthy plant foods.
Over 4,833,042 person-years of follow-up, we documented 8,631 incident CHD cases. In pooled multivariable analysis, higher adherence to PDI was independently inversely associated with CHD (hazard ratio HR comparing extreme deciles: 0.92; 95% confidence interval CI: 0.83 to 1.01; p trend = 0.003). This inverse association was stronger for hDPI (HR: 0.75; 95% CI: 0.68 to 0.83; p trend <0.001). Conversely, uPDI was positively associated with CHD (HR: 1.32; 95% CI: 1.20 to 1.46; p trend <0.001).
Higher intake of a plant-based diet index rich in healthier plant foods is associated with substantially lower CHD risk, whereas a plant-based diet index that emphasizes less-healthy plant foods is associated with higher CHD risk.
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Critical limb ischemia, first defined in 1982, was intended to delineate a subgroup of patients with a threatened lower extremity primarily because of chronic ischemia. It was the intent of the ...original authors that patients with diabetes be excluded or analyzed separately. The Fontaine and Rutherford Systems have been used to classify risk of amputation and likelihood of benefit from revascularization by subcategorizing patients into two groups: ischemic rest pain and tissue loss. Due to demographic shifts over the last 40 years, especially a dramatic rise in the incidence of diabetes mellitus and rapidly expanding techniques of revascularization, it has become increasingly difficult to perform meaningful outcomes analysis for patients with threatened limbs using these existing classification systems. Particularly in patients with diabetes, limb threat is part of a broad disease spectrum. Perfusion is only one determinant of outcome; wound extent and the presence and severity of infection also greatly impact the threat to a limb. Therefore, the Society for Vascular Surgery Lower Extremity Guidelines Committee undertook the task of creating a new classification of the threatened lower extremity that reflects these important considerations. We term this new framework, the Society for Vascular Surgery Lower Extremity Threatened Limb Classification System. Risk stratification is based on three major factors that impact amputation risk and clinical management: Wound, Ischemia, and foot Infection (WIfI). The implementation of this classification system is intended to permit more meaningful analysis of outcomes for various forms of therapy in this challenging, but heterogeneous population.
Current evidence on associations between intakes of linoleic acid (LA), the predominant n–6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized by a systematic review and ...meta-analysis.
The aim was to perform a systematic review and meta-analysis of prospective cohort studies to examine associations between LA intake and mortality.
We conducted a comprehensive search of MEDLINE and EMBASE databases through 31 July 2019 for prospective cohort studies reporting associations of LA (assessed by dietary surveys and/or LA concentrations in adipose tissue or blood compartments) with mortality from all causes, cardiovascular disease (CVD), and cancer. Multivariable-adjusted RRs were pooled using random-effects meta-analysis.
Thirty-eight studies reporting 44 prospective cohorts were identified; these included 811,069 participants with dietary intake assessment (170,076 all-cause, 50,786 CVD, and 59,684 cancer deaths) and 65,411 participants with biomarker measurements (9758 all-cause, 6492 CVD, and 1719 cancer deaths). Pooled RRs comparing extreme categories of dietary LA intake (high vs low) were 0.87 (95% CI: 0.81, 0.94; I2= 67.9%) for total mortality, 0.87 (95% CI: 0.82, 0.92; I2= 3.7%) for CVD mortality, and 0.89 (95% CI: 0.85, 0.93; I2= 0%) for cancer mortality. Pooled RRs for each SD increment in LA concentrations in adipose tissue/blood compartments were 0.91 (95% CI: 0.87, 0.95; I2= 64.1%) for total mortality, 0.89 (95% CI: 0.85, 0.94; I2= 28.9%) for CVD mortality, and 0.91 (95% CI: 0.84, 0.98; I2= 26.3%) for cancer mortality. Meta-regressions suggested baseline age and dietary assessment methods as potential sources of heterogeneity for the association between LA and total mortality.
In prospective cohort studies, higher LA intake, assessed by dietary surveys or biomarkers, was associated with a modestly lower risk of mortality from all causes, CVD, and cancer. These data support the potential long-term benefits of PUFA intake in lowering the risk of CVD and premature death.
Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted.
To conduct an updated ...systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes.
We searched PubMed and Embase until 6 March 2021.
We selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes.
Baseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies.
A total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate-corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07-2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69-0.90).
Substantial heterogeneity (I2 > 50%, τ2 > 0.1) was observed for some of the metabolites.
Several plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.
Recent attention has focused on fructose as having a unique role in the pathogenesis of cardiometabolic diseases. However, because we rarely consume fructose in isolation, the major source of ...fructose in the diet comes from fructose-containing sugars, sucrose and high fructose corn syrup, in sugar-sweetened beverages and foods. Intake of sugar-sweetened beverages has been consistently linked to increased risk of obesity, type 2 diabetes, and cardiovascular disease in various populations. Putative underlying mechanisms include incomplete compensation for liquid calories, adverse glycemic effects, and increased hepatic metabolism of fructose leading to de novo lipogenesis, production of uric acid, and accumulation of visceral and ectopic fat. In this review we summarize the epidemiological and clinical trial evidence evaluating added sugars, especially sugar-sweetened beverages, and the risk of obesity, diabetes, and cardiovascular disease and address potential biological mechanisms with an emphasis on fructose physiology. We also discuss strategies to reduce intake of fructose-containing beverages.
The ATR replication checkpoint ensures that stalled forks remain stable when replisome movement is impeded. Using an improved iPOND protocol combined with SILAC mass spectrometry, we characterized ...human replisome dynamics in response to fork stalling. Our data provide a quantitative picture of the replisome and replication stress response proteomes in 32 experimental conditions. Importantly, rather than stabilize the replisome, the checkpoint prevents two distinct types of fork collapse. Unsupervised hierarchical clustering of protein abundance on nascent DNA is sufficient to identify protein complexes and place newly identified replisome-associated proteins into functional pathways. As an example, we demonstrate that ZNF644 complexes with the G9a/GLP methyltransferase at replication forks and is needed to prevent replication-associated DNA damage. Our data reveal how the replication checkpoint preserves genome integrity, provide insights into the mechanism of action of ATR inhibitors, and will be a useful resource for replication, DNA repair, and chromatin investigators.
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•iPOND-SILAC-MS across experimental perturbations identifies protein complexes•ZNF644 forms a complex with G9a/GLP at replication forks•Replisome stabilization is not a major function of the replication checkpoint•The replication checkpoint prevents two distinct types of fork collapse
Dungrawala et al. use quantitative iPOND-mass spectrometry analysis of proteins associated with nascent DNA during replication stress to understand how the replication checkpoint controls the replisome and replication stress response.
Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of ...α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.
For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.
A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all
< 0.001). ALA was not associated with T2D (HR 0.97 95% CI 0.92, 1.02) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.
Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.
Purpose of Review
To examine recent literature on dairy products, dairy fatty acids, and cardiometabolic disease. Primary questions of interest include what unique challenges researchers face when ...investigating dairy products/biomarkers, whether one should consume dairy to reduce disease risk, whether dairy fatty acids may be beneficial for health, and whether one should prefer low- or high-fat dairy products.
Recent Findings
Dairy composes about 10% of the calories in a typical American diet, about half of that coming from fluid milk, half coming from cheese, and small amounts from yogurt. Most meta-analyses report no or weak inverse association between dairy intake with cardiovascular disease and related intermediate outcomes. There is some suggestion that dairy consumption was inversely associated with stroke incidence and yogurt consumption was associated with lower risk of type 2 diabetes. Odd chain fatty acids (OCFAs) found primarily in dairy (15:0 and 17:0) appear to be inversely associated with cardiometabolic risk, but causation is uncertain. Substitution analyses based on prospective cohorts suggested that replacing dairy fat with vegetable fat or polyunsaturated fat was associated with significantly lower risk of cardiovascular disease.
Summary
Current evidence suggests null or weak inverse association between consumption of dairy products and risk of cardiovascular disease. However, replacing dairy fat with polyunsaturated fat, especially from plant-based foods, may confer health benefits. More research is needed to examine health effects of different types of dairy products in diverse populations.
Spatial restriction of mRNA to distinct subcellular locations enables local regulation and synthesis of proteins. However, the organizing principles of mRNA localization remain poorly understood. ...Here we analyzed subcellular transcriptomes of neural projections and soma of primary mouse cortical neurons and two neuronal cell lines and found that alternative last exons (ALEs) often confer isoform-specific localization. Surprisingly, gene-distal ALE isoforms were four times more often localized to neurites than gene-proximal isoforms. Localized isoforms were induced during neuronal differentiation and enriched for motifs associated with muscleblind-like (Mbnl) family RNA-binding proteins. Depletion of Mbnl1 and/or Mbnl2 reduced localization of hundreds of transcripts, implicating Mbnls in localization of mRNAs to neurites. We provide evidence supporting a model in which the linkage between genomic position of ALEs and subcellular localization enables coordinated induction of localization-competent mRNA isoforms through a post-transcriptional regulatory program that is induced during differentiation and reversed in cellular reprogramming and cancer.
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•Alternative mRNA isoforms of a gene often differ in subcellular localization•Gene-distal alternative last exon isoforms preferentially localize to neurites•A shift toward gene-distal last exon isoforms occurs during differentiation•Neurite localization of mRNAs often depends on expression of Mbnl proteins
Taliaferro et al. show that mRNA isoforms that contain gene-distal alternative last exons are preferentially localized to neurites. These isoforms are induced during neuronal differentiation, suggesting that a coordinated post-transcriptional program targets messages to neurites. Localization of many neuronal mRNAs depends on muscleblind proteins.
Vertebrate red blood cells (RBCs) seem to serve tissue oxygen delivery in two distinct ways. Firstly, RBCs enable the adequate transport of O(2) between respiratory surfaces and metabolizing tissues ...by means of their high intracellular concentration of hemoglobin (Hb), appropriate allosteric interactions between Hb ligand-binding sites, and an adjustable intracellular chemical environment that allows fine-tuning of Hb O(2) affinity. Secondly, RBCs may sense tissue O(2) requirements via their degree of deoxygenation when they travel through the microcirculation and release vasodilatory compounds that enhance blood flow in hypoxic tissues. This latter function could be important in matching tissue O(2) delivery with local O(2) demand. Three main mechanisms by which RBCs can regulate their own distribution in the microcirculation have been proposed. These are: (1) deoxygenation-dependent release of ATP from RBCs, which stimulates production of nitric oxide (NO) and other vasodilators in the endothelium; (2) release of vasoactive NO from S-nitroso-Hb upon deoxygenation; and (3) reduction of naturally occurring nitrite to vasoactive NO by deoxygenated Hb. This Commentary inspects all three hypotheses with regard to their mechanisms, experimental evidence in their support and details that remain unresolved. The prime focus is on human/mammalian models, where most evidence for a role of erythrocyte ATP and NO release in blood flow regulation have accumulated. Information from other vertebrate groups is integrated in the analysis and used to discuss the evolutionary origin and general relevance of each hypothesis.
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