A Review of Bioactive Compound Effects from Primary Legume Protein Sources in Human and Animal Health.

The global demand for sustainable and nutritious food sources has catalyzed interest in legumes, known for their rich repertoire of health-promoting compounds. This review delves into the diverse array of bioactive peptides, protein subunits, isoflavones, antinutritional factors, and saponins found in the primary legume protein sources-soybeans, peas, chickpeas, and mung beans. The current state of research on these compounds is critically evaluated, with an emphasis on the potential health benefits, ranging from antioxidant and anticancer properties to the management of chronic diseases such as diabetes and hypertension. The extensively studied soybean is highlighted and the relatively unexplored potential of other legumes is also included, pointing to a significant, underutilized resource for developing health-enhancing foods. The review advocates for future interdisciplinary research to further unravel the mechanisms of action of these bioactive compounds and to explore their synergistic effects. The ultimate goal is to leverage the full spectrum of benefits offered by legumes, not only to advance human health but also to contribute to the sustainability of food systems. By providing a comprehensive overview of the nutraceutical potential of legumes, this manuscript sets a foundation for future investigations aimed at optimizing the use of legumes in the global pursuit of health and nutritional security.

Rehabilitation and return to sport criteria following surgical treatment of osteochondritis dissecans of the capitellum: a systematic review.

Background: Osteochondritis dissecans (OCD) of the capitellum is a well-described condition that most commonly affects adolescent throwing athletes and gymnasts. There is no gold standard rehabilitation protocol or timing for return to sport (RTS) after surgical management of OCD of the capitellum. Hypothesis/Purpose: The purpose of the study was to identify in the existing literature any criteria used for RTS following surgical treatment of OCD of the capitellum. The hypothesis was that surgeons would utilize length of time rather than functional criteria or performance benchmarks for RTS. Methods: Level 1 to 4 studies evaluating athletes who underwent surgery for OCD of the capitellum with a minimum follow-up of 1-year were included. Studies not describing RTS criteria, including less than 1-year follow-up, non-operative management only, and revision procedures were excluded. Each study was analyzed for RTS criteria, RTS rate, RTS timeline, sport played, level of competition, graft source (if utilized), and postoperative rehabilitation parameters. Assessment of bias and methodological quality was performed using the Coleman methodology score and RTS value assessment. Results: All studies reported a rehabilitation protocol with immobilization followed by bracing with progressive range of motion. RTS rate was 80.9% (233/288). The majority of studies reported using time-based criteria for RTS (11/15). The most commonly reported timeline was 6 months (range: 3-12 months). Conclusion: The overall RTS rate after surgical treatment of capitellar OCD is high with no consensus on RTS criteria. The two most consistent RTS criteria reported in the literature are return of elbow range of motion and healing demonstrated on postoperative imaging. There is a wide range of time to RTS in the literature, which may be sport dependent. Further research is needed to develop functional and performance-based metrics to better standardize RTS criteria and rehabilitation protocols.

Soybean genetics, genomics, and breeding for improving nutritional value and reducing antinutritional traits in food and feed.

Soybean [Glycine max (L.) Merr.] is a globally important crop due to its valuable seed composition, versatile feed, food, and industrial end-uses, and consistent genetic gain. Successful genetic gain in soybean has led to widespread adaptation and increased value for producers, processors, and consumers. Specific focus on the nutritional quality of soybean seed composition for food and feed has further elucidated genetic knowledge and bolstered breeding progress. Seed components are historical and current targets for soybean breeders seeking to improve nutritional quality of soybean. This article reviews genetic and genomic foundations for improvement of nutritionally important traits, such as protein and amino acids, oil and fatty acids, carbohydrates, and specific food-grade considerations; discusses the application of advanced breeding technology such as CRISPR/Cas9 in creating seed composition variations; and provides future directions and breeding recommendations regarding soybean seed composition traits.

Determining Genetic Markers and Seed Compositions Related to High Test Weight in Glycine max.

Test weight, one of the primary indicators of soybean seed quality, is measured as the amount of soybean seeds in kilograms that can fit into one hectoliter. The price that growers receive for their soybean is dependent on test weight. Over the past 50 years, growers have observed a decreasing trend in test weight. Therefore, it is imperative to understand better the relationship between soybean test weight and other traits to enable breeders to select parental lines with high test weights in breeding programs to ensure the grower's profitability. The objectives of the study were to identify genetic markers associated with high test weight in soybean and to determine the correlation between high test weight and five important seed composition traits (protein, oil, sucrose, raffinose, and stachyose content). Maturity group IV and V germplasms from the USDA soybean germplasm collection were grown in Blacksburg and Warsaw in Virginia from 2019 to 2021 and were measured for all of the above traits. Results show that test weight values ranged from 62-77 kg/hL over the three years. Multiple single-nucleotide polymorphisms (SNPs) significantly associated with high test weight were found on chromosome (Chr.) 15 along with a couple on chromosome 14, and 11 candidate genes were found near these SNPs. Test weight was found to be significantly negatively correlated with oil content, inconsistently correlated with protein content in all environments, and negatively correlated but not significantly with all three sugars except for raffinose in Blacksburg 2019. We concluded that the genes that underlie test weight might be on chromosome 15, and the validated associated SNPs might be used to assist breeding selection of test weight. Breeders should pay special attention to test weight while selecting for high oil content in soybean due to their negative correlation.

A novel non-invasive method for predicting bone mineral density and fracture risk using demographic and anthropometric measures.

Fractures are costly to treat and can significantly increase morbidity. Although dual-energy x-ray absorptiometry (DEXA) is used to screen at risk people with low bone mineral density (BMD), not all areas have access to one. We sought to create a readily accessible, inexpensive, high-throughput prediction tool for BMD that may identify people at risk of fracture for further evaluation. Anthropometric and demographic data were collected from 492 volunteers (♂275, ♀217; [44 â€‹± â€‹20] years; Body Mass Index (BMI) = [27.6 â€‹± â€‹6.0] kg/m2) in addition to total body bone mineral content (BMC, kg) and BMD measurements of the spine, pelvis, arms, legs and total body. Multiple-linear-regression with step-wise removal was used to develop a two-step prediction model for BMC followed by BMC. Model selection was determined by the highest adjusted R2, lowest error of estimate, and lowest level of variance inflation (α â€‹= â€‹0.05). Height (HTcm), age (years), sexm=1, f=0, %body fat (%fat), fat free mass (FFMkg), fat mass (FMkg), leg length (LLcm), shoulder width (SHWDTHcm), trunk length (TRNKLcm), and pelvis width (PWDTHcm) were observed to be significant predictors in the following two-step model (p â€‹< â€‹0.05). Step1: BMC (kg) = (0.006 3 × HT) â€‹+ â€‹(-0.002 4 × AGE) â€‹+ â€‹(0.171 2 × SEXm=1, f=0) â€‹+ â€‹(0.031 4 × FFM) â€‹+ â€‹(0.001 × FM) â€‹+ â€‹(0.008 9 × SHWDTH) â€‹+ â€‹(-0.014 5 × TRNKL) â€‹+ â€‹(-0.027 8 × PWDTH) - 0.507 3; R2 â€‹= â€‹0.819, SE â€‹± â€‹0.301. Step2: Total body BMD (g/cm2) = (-0.002 8 × HT) â€‹+ â€‹(-0.043 7 × SEXm=1, f=0) â€‹+ â€‹(0.000 8 × %FAT) â€‹+ â€‹(0.297 0 × BMC) â€‹+ â€‹(-0.002 3 × LL) â€‹+ â€‹(0.002 3 × SHWDTH) â€‹+ â€‹(-0.002 5 × TRNKL) â€‹+ â€‹(-0.011 3 × PWDTH) â€‹+ â€‹1.379; R2 â€‹= â€‹0.89, SE â€‹± â€‹0.054. Similar models were also developed to predict leg, arm, spine, and pelvis BMD (R2 â€‹= â€‹0.796-0.864, p â€‹< â€‹0.05). The equations developed here represent promising tools for identifying individuals with low BMD at risk of fracture who would benefit from further evaluation, especially in the resource or time restricted setting.

Genome-Wide Association Study and Genomic Selection for Proteinogenic Methionine in Soybean Seeds.

Soybean [Glycine max (L.) Merr.] seeds have an amino acid profile that provides excellent viability as a food and feed protein source. However, low concentrations of an essential amino acid, methionine, limit the nutritional utility of soybean protein. The objectives of this study were to identify genomic associations and evaluate the potential for genomic selection (GS) for methionine content in soybean seeds. We performed a genome-wide association study (GWAS) that utilized 311 soybean accessions from maturity groups IV and V grown in three locations in 2018 and 2019. A total of 35,570 single nucleotide polymorphisms (SNPs) were used to identify genomic associations with proteinogenic methionine content that was quantified by high-performance liquid chromatography (HPLC). Across four environments, 23 novel SNPs were identified as being associated with methionine content. The strongest associations were found on chromosomes 3 (ss715586112, ss715586120, ss715586126, ss715586203, and ss715586204), 8 (ss715599541 and ss715599547) and 16 (ss715625009). Several gene models were recognized within proximity to these SNPs, such as a leucine-rich repeat protein kinase and a serine/threonine protein kinase. Identification of these linked SNPs should help soybean breeders to improve protein quality in soybean seeds. GS was evaluated using k-fold cross validation within each environment with two SNP sets, the complete 35,570 set and a subset of 248 SNPs determined to be associated with methionine through GWAS. Average prediction accuracy (r 2) was highest using the SNP subset ranging from 0.45 to 0.62, which was a significant improvement from the complete set accuracy that ranged from 0.03 to 0.27. This indicated that GS utilizing a significant subset of SNPs may be a viable tool for soybean breeders seeking to improve methionine content.

Genome-wide association analysis of sucrose and alanine contents in edamame beans.

The sucrose and Alanine (Ala) content in edamame beans significantly impacts the sweetness flavor of edamame-derived products as an important attribute to consumers' acceptance. Unlike grain-type soybeans, edamame beans are harvested as fresh beans at the R6 to R7 growth stages when beans are filled 80-90% of the pod capacity. The genetic basis of sucrose and Ala contents in fresh edamame beans may differ from those in dry seeds. To date, there is no report on the genetic basis of sucrose and Ala contents in the edamame beans. In this study, a genome-wide association study was conducted to identify single nucleotide polymorphisms (SNPs) related to sucrose and Ala levels in edamame beans using an association mapping panel of 189 edamame accessions genotyped with a SoySNP50K BeadChip. A total of 43 and 25 SNPs was associated with sucrose content and Ala content in the edamame beans, respectively. Four genes (Glyma.10g270800, Glyma.08g137500, Glyma.10g268500, and Glyma.18g193600) with known effects on the process of sucrose biosynthesis and 37 novel sucrose-related genes were characterized. Three genes (Gm17g070500, Glyma.14g201100 and Glyma.18g269600) with likely relevant effects in regulating Ala content and 22 novel Ala-related genes were identified. In addition, by summarizing the phenotypic data of edamame beans from three locations in two years, three PI accessions (PI 532469, PI 243551, and PI 407748) were selected as the high sucrose and high Ala parental lines for the perspective breeding of sweet edamame varieties. Thus, the beneficial alleles, candidate genes, and selected PI accessions identified in this study will be fundamental to develop edamame varieties with improved consumers' acceptance, and eventually promote edamame production as a specialty crop in the United States.

Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors.

Targeted polypharmacology provides an efficient method of treating diseases such as cancer with complex, multigenic causes provided that compounds with advantageous activity profiles can be discovered. Novel covalent TAK1 inhibitors were validated in cellular contexts for their ability to inhibit the TAK1 kinase and for their polypharmacology. Several inhibitors phenocopied reported TAK1 inhibitor 5Z-7-oxozaenol with comparable efficacy and complementary kinase selectivity profiles. Compound 5 exhibited the greatest potency in RAS-mutated and wild-type RAS cell lines from various cancer types. A biotinylated derivative of 5, 27, was used to verify TAK1 binding in cells. The newly described inhibitors constitute useful tools for further development of multi-targeting TAK1-centered inhibitors for cancer and other diseases.

Structural and Biochemical Analyses Reveal the Mechanism of Glutathione S-Transferase Pi 1 Inhibition by the Anti-cancer Compound Piperlongumine.

Glutathione S-transferase pi 1 (GSTP1) is frequently overexpressed in cancerous tumors and is a putative target of the plant compound piperlongumine (PL), which contains two reactive olefins and inhibits proliferation in cancer cells but not normal cells. PL exposure of cancer cells results in increased reactive oxygen species and decreased GSH. These data in tandem with other information led to the conclusion that PL inhibits GSTP1, which forms covalent bonds between GSH and various electrophilic compounds, through covalent adduct formation at the C7-C8 olefin of PL, whereas the C2-C3 olefin of PL was postulated to react with GSH. However, direct evidence for this mechanism has been lacking. To investigate, we solved the X-ray crystal structure of GSTP1 bound to PL and GSH at 1.1 Å resolution to rationalize previously reported structure activity relationship studies. Surprisingly, the structure showed that a hydrolysis product of PL (hPL) was conjugated to glutathione at the C7-C8 olefin, and this complex was bound to the active site of GSTP1; no covalent bond formation between hPL and GSTP1 was observed. Mass spectrometry (MS) analysis of the reactions between PL and GSTP1 confirmed that PL does not label GSTP1. Moreover, MS data also indicated that nucleophilic attack on PL at the C2-C3 olefin led to PL hydrolysis. Although hPL inhibits GSTP1 enzymatic activity in vitro, treatment of cells susceptible to PL with hPL did not have significant anti-proliferative effects, suggesting that hPL is not membrane-permeable. Altogether, our data suggest a model wherein PL is a prodrug whose intracellular hydrolysis initiates the formation of the hPL-GSH conjugate, which blocks the active site of and inhibits GSTP1 and thereby cancer cell proliferation.

Effect of a 6-month vegan low-carbohydrate ('Eco-Atkins') diet on cardiovascular risk factors and body weight in hyperlipidaemic adults: a randomised controlled trial.

OBJECTIVE: Low-carbohydrate diets may be useful for weight loss. Diets high in vegetable proteins and oils may reduce the risk of coronary heart disease. The main objective was to determine the longer term effect of a diet that was both low-carbohydrate and plant-based on weight loss and low-density lipoprotein cholesterol (LDL-C). DESIGN, SETTING, PARTICIPANTS: A parallel design study of 39 overweight hyperlipidaemic men and postmenopausal women conducted at a Canadian university-affiliated hospital nutrition research centre from April 2005 to November 2006. INTERVENTION: Participants were advised to consume either a low-carbohydrate vegan diet or a high-carbohydrate lacto-ovo vegetarian diet for 6 months after completing 1-month metabolic (all foods provided) versions of these diets. The prescribed macronutrient intakes for the low-carbohydrate and high-carbohydrate diets were: 26% and 58% of energy from carbohydrate, 31% and 16% from protein and 43% and 25% from fat, respectively. PRIMARY OUTCOME: Change in body weight. RESULTS: 23 participants (50% test, 68% control) completed the 6-month ad libitum study. The approximate 4 kg weight loss on the metabolic study was increased to -6.9 kg on low-carbohydrate and -5.8 kg on high-carbohydrate 6-month ad libitum treatments (treatment difference (95% CI) -1.1 kg (-2.1 to 0.0), p=0.047). The relative LDL-C and triglyceride reductions were also greater on the low-carbohydrate treatment (treatment difference (95% CI) -0.49 mmol/L (-0.70 to -0.28), p<0.001 and -0.34 mmol/L (-0.57 to -0.11), p=0.005, respectively), as were the total cholesterol:HDL-C and apolipoprotein B:A1 ratios (-0.57 (-0.83, -0.32), p<0.001 and -0.05 (-0.09, -0.02), p=0.003, respectively). CONCLUSIONS: A self-selected low-carbohydrate vegan diet, containing increased protein and fat from gluten and soy products, nuts and vegetable oils, had lipid lowering advantages over a high-carbohydrate, low-fat weight loss diet, thus improving heart disease risk factors. TRIAL REGISTRATION: clinicaltrials.gov (http://www.clinicaltrials.gov/), #NCT00256516.

Increased dietary cholesterol promotes enhanced mutagenesis in DNA polymerase kappa-deficient mice.

DNA polymerase kappa (Polκ) bypasses planar polycyclic N2-guanine adducts in an error-free manner. Cholesterol derivatives may interact with DNA to form similarly bulky lesions. In accordance, these studies examined whether increased mutagenesis of DNA accompanies hypercholesterolemia in Polk-/- mice. These mice also carried apoE gene knockouts to ensure increased levels of plasma cholesterol following exposure to a high cholesterol diet. The mice carried a reporter transgene (the λ-phage cII gene) for subsequent quantitative analysis of mutagenesis in various tissues. We observed significantly increased mutation frequencies in several organs of apoE-/-Polk-/- mice following a high cholesterol diet, compared to those remaining on a standard diet. Regardless of dietary regime, the mutation frequency in many organs was significantly higher in apoE-/-Polk-/- than in apoE-/-Polk+/+ mice. As expected for polycyclic guanine adducts, the mutations mainly consisted of G:C transversions. The life expectancy of apoE-/-Polk-/- mice maintained on a high cholesterol diet was reduced compared to apoE-/-Polk+/+ mice. Overall, this study demonstrates a role for Polκ in bypass of cholesterol-induced guanine lesions.

Equol status and blood lipid profile in hyperlipidemia after consumption of diets containing soy foods.

BACKGROUND: Recent analyses have challenged the effectiveness of soy foods as part of a cardiovascular risk reduction diet. OBJECTIVE: The objective of the study was to show whether equol status determines the effectiveness of soy foods to lower LDL cholesterol and to raise HDL cholesterol. DESIGN: Eighty-five hypercholesterolemic men and postmenopausal women (42 men, 43 women) participated in 1 of 3 studies that represented a range of soy interventions and that followed the same general protocol at a Canadian university hospital research center. Soy foods were provided for 1 mo at doses of 30-52 g/d for the 3 studies as follows: 1) soy foods with either high-normal (73 mg/d) or low (10 mg/d) isoflavones, 2) soy foods with or without a prebiotic to enhance colonic fermentation (10 g polyfructans/d), or 3) soy foods with a low-carbohydrate diet (26% carbohydrate). Studies 1 and 2 were randomized controlled crossover trials, and study 3 was a parallel study. RESULTS: The separation of the group into equol producers (n = 30) and nonproducers (n = 55) showed similar reductions from baseline in LDL cholesterol (-9.3 ± 2.5% and -11.1 ± 1.6%, respectively; P = 0.834), with preservation of HDL cholesterol and apolipoprotein A-I only in equol producers compared with reductions in nonproducers (HDL cholesterol: +0.9 ± 2.7% compared with -4.3 ± 1.1%, P = 0.006; apolipoprotein A-I: -1.0 ± 1.1% compared with -4.7 ± 1.0%; P = 0.011). The amount of urinary equol excreted did not relate to the changes in blood lipids. CONCLUSIONS: Soy foods reduced serum LDL cholesterol equally in both equol producers and nonproducers. However, in equol producers, ~35% of our study population, soy consumption had the added cardiovascular benefit of maintaining higher HDL-cholesterol concentrations than those seen in equol nonproducers. This trial was registered at clinicaltrials.gov as NCT00877825 (study 1), NCT00516594 (study 2), and NCT00256516 (study 3).

The effect of a plant-based low-carbohydrate ("Eco-Atkins") diet on body weight and blood lipid concentrations in hyperlipidemic subjects.

BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.

The effect of strawberries in a cholesterol-lowering dietary portfolio.

Effective diets reduce blood lipids and oxidative damage, both of which have been linked to the complications of diabetes and coronary heart disease. Our objective was to assess the effect of adding strawberries, as a source of antioxidants, to improve the antioxidant effect of a cholesterol-lowering diet (dietary portfolio). To this end, 28 hyperlipidemic subjects who had followed the dietary portfolio consisting of soy, viscous fiber, plant sterol, and nuts for a mean of 2.5 years were randomized to receive supplements of strawberries (454 g/d, 112 kcal) or additional oat bran bread (65 g/d, 112 kcal, approximately 2 g beta-glucan) (control) in a randomized 1-month crossover study with a 2-week washout. Strawberry supplementation resulted in a greater reduction in oxidative damage to low-density lipoprotein (LDL) measured as thiobarbituric acid-reactive substances in the LDL fraction (P = .014). At the end of the strawberry period, reductions in LDL cholesterol and in the ratio of total to high-density lipoprotein cholesterol were maintained close to 1-year values at -13.4% +/- 2.1% and -15.2% +/- 1.7%, respectively (P < .001), and were similar to the post-oat bran bread values. Strawberries also improved the palatability of the diet. We conclude that strawberry supplementation reduced oxidative damage to LDL while maintaining reductions in blood lipids and enhancing diet palatability. Added fruit may improve the overall utility of diets designed to lower coronary heart disease risk.

Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF.

G12 class heterotrimeric G proteins stimulate RhoA activation by RGS-RhoGEFs. However, p115RhoGEF is a GTPase Activating Protein (GAP) toward Galpha13, whereas PDZRhoGEF is not. We have characterized the interaction between the PDZRhoGEF rgRGS domain (PRG-rgRGS) and the alpha subunit of G13 and have determined crystal structures of their complexes in both the inactive state bound to GDP and the active states bound to GDP*AlF (transition state) and GTPgammaS (Michaelis complex). PRG-rgRGS interacts extensively with the helical domain and the effector-binding sites on Galpha13 through contacts that are largely conserved in all three nucleotide-bound states, although PRG-rgRGS has highest affinity to the Michaelis complex. An acidic motif in the N terminus of PRG-rgRGS occupies the GAP binding site of Galpha13 and is flexible in the GDP*AlF complex but well ordered in the GTPgammaS complex. Replacement of key residues in this motif with their counterparts in p115RhoGEF confers GAP activity.

Effect of almonds on insulin secretion and insulin resistance in nondiabetic hyperlipidemic subjects: a randomized controlled crossover trial.

Nuts appear to have a marked effect in cohort studies in reducing the risk of coronary heart disease (CHD), but their demonstrated ability to lower cholesterol can only explain a proportion of the reduction in risk. Our aim was to assess whether improvement in carbohydrate metabolism provides a further explanation for the effect of nuts in reducing CHD. The effects of whole almonds, taken as snacks, were compared with the effects of low saturated fat (<5% energy) whole-wheat muffins (control) in the therapeutic diets of hyperlipidemic subjects. In a randomized crossover study, 27 hyperlipidemic men and women consumed 3 isoenergetic (mean, 423 kcal/d) supplements each for 1 month. Supplements provided 22.2% of energy and consisted of full-dose almonds (73 +/- 3 g/d), half-dose almonds plus half-dose muffins, and full-dose muffins. Subjects were assessed at weeks 0, 2, and 4 and fasting blood samples were obtained. Twenty-four-hour urinary output was collected at the end of week 4 on each treatment. Mean body weights differed by less than 300 g between treatments. No differences were seen in baseline or treatment values for fasting glucose, insulin, C-peptide, or insulin resistance as measured by homeostasis model assessment of insulin resistance. However, 24-hour urinary C-peptide output as a marker of 24-hour insulin secretion was significantly reduced on the half-and full-dose almonds by comparison to the control after adjustment for urinary creatinine output (P = .002 and P = .004, respectively). We conclude that reductions in 24-hour insulin secretion appear to be a further metabolic advantage of nuts that in the longer term may help to explain the association of nut consumption with reduced CHD risk.

Effect of plant sterols in combination with other cholesterol-lowering foods.

The National Cholesterol Education Program Adult Treatment Panel III guidelines advocate effective combinations of cholesterol-lowering dietary components. This approach (dietary portfolio) produces large reductions in serum cholesterol, but the contribution of individual components remains to be established. We therefore assessed the effect of eliminating one out of the 4 dietary portfolio components. Plant sterols were selected because at 2 g/d, they have been reported to reduce low-density lipoprotein cholesterol (LDL-C) by 9% to 14%. Forty-two hyperlipidemic subjects were prescribed diets high in soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal) for 80 weeks. Subjects were instructed to take these together with plant sterols (1.0 g/1000 kcal) except between weeks 52 and 62. While taking the full dietary portfolio, including plant sterols, mean LDL-C reduction from baseline was 15.4% +/- 1.6% (P < .001). After sterol elimination, mean LDL-C reduction was 9.0% +/- 1.5% (P < .001). Comparable LDL-C reductions were also seen for the 18 subjects with a complete data set: on plant sterols, 16.7% +/- 3.1% (P < .001) and off plant sterols, 10.3% +/- 2.6% (P < .001), resulting in a 6.3% +/- 2.0% (P = .005) difference attributable to plant sterols. Compliance in this group of 18 was 67.0% +/- 5.9% for plant sterols and 61.9% +/- 4.8% for the other components. In combination with other cholesterol-lowering foods and against the background of a low-saturated fat diet, plant sterols contributed over one third of the LDL-C reduction seen with the dietary portfolio after 1 year of following dietary advice.

Regulation of Rho guanine nucleotide exchange factors by G proteins.

Monomeric Rho GTPases regulate cellular dynamics through remodeling of the cytoskeleton, modulation of immediate signaling pathways, and longer-term regulation of gene transcription. One family of guanine nucleotide exchange factors for Rho proteins (RhoGEFs) provides a direct pathway for regulation of RhoA by cell surface receptors coupled to heterotrimeric G proteins. Some of these RhoGEFs also contain RGS domains that can attenuate signaling by the G(12) and G(13) proteins. The regulation provided by these RhoGEFs is defined by their selective regulation by specific G proteins, phosphorylation by kinases, and potential localization with signaling partners. Evidence of their physiological importance is derived from gene knockouts in Drosophila and mice. Current understanding of the basic regulatory mechanisms of these RhoGEFs is discussed. An overview of identified interactions with other signaling proteins suggests the growing spectrum of their involvement in numerous signaling pathways.

Assessment of the longer-term effects of a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia.

BACKGROUND: Cholesterol-lowering foods may be more effective when consumed as combinations rather than as single foods. OBJECTIVES: Our aims were to determine the effectiveness of consuming a combination of cholesterol-lowering foods (dietary portfolio) under real-world conditions and to compare these results with published data from the same participants who had undergone 4-wk metabolic studies to compare the same dietary portfolio with the effects of a statin. DESIGN: For 12 mo, 66 hyperlipidemic participants were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal). Fifty-five participants completed the 1-y study. The 1-y data were also compared with published results on 29 of the participants who had also undergone separate 1-mo metabolic trials of a diet and a statin. RESULTS: At 3 mo and 1 y, mean (+/-SE) LDL-cholesterol reductions appeared stable at 14.0 +/- 1.6% (P < 0.001) and 12.8 +/- 2.0% (P < 0.001), respectively (n = 66). These reductions were less than those observed after the 1-mo metabolic diet and statin trials. Nevertheless, 31.8% of the participants (n = 21 of 66) had LDL-cholesterol reductions of >20% at 1 y (x +/- SE: -29.7 +/- 1.6%). The LDL-cholesterol reductions in this group were not significantly different from those seen after their respective metabolically controlled portfolio or statin treatments. A correlation was found between total dietary adherence and LDL-cholesterol change (r = -0.42, P < 0.001). Only 2 of the 26 participants with <55% compliance achieved LDL-cholesterol reductions >20% at 1 y. CONCLUSIONS: More than 30% of motivated participants who ate the dietary portfolio of cholesterol-lowering foods under real-world conditions were able to lower LDL-cholesterol concentrations >20%, which was not significantly different from their response to a first-generation statin taken under metabolically controlled conditions.

Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants.

BACKGROUND: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol. Newer dietary approaches combining cholesterol-lowering foods may offer another option, but these approaches have not been compared directly with statins in the same persons. OBJECTIVE: The objective was to compare, in the same subjects, the cholesterol-lowering potential of a dietary portfolio with that of a statin. DESIGN: Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in random order as outpatients: a very-low-saturated-fat diet (control diet), the same diet plus 20 mg lovastatin (statin diet), and a diet high in plant sterols (1.0 g/1000 kcal), soy-protein foods (including soy milks and soy burgers, 21.4 g/1000 kcal), almonds (14 g/1000 kcal), and viscous fibers from oats, barley, psyllium, and the vegetables okra and eggplant (10 g/1000 kcal) (portfolio diets). Fasting blood samples were obtained at 0, 2, and 4 wk. RESULTS: LDL-cholesterol concentrations decreased by 8.5+/-1.9%, 33.3+/-1.9%, and 29.6+/-1.3% after 4 wk of the control, statin, and portfolio diets, respectively. Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk (P=0.013), 9 participants (26%) achieved their lowest LDL-cholesterol concentrations with the portfolio diet. Moreover, the statin (n=27) and the portfolio (n=24) diets did not differ significantly (P=0.288) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff. CONCLUSIONS: Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention. They may, therefore, bridge the treatment gap between current therapeutic diets and newer statins.