miR-92a-3p regulates ethanol-induced apoptosis in H9c2 cardiomyocytes.

The role of miR-92a-3p in the ethanol-induced apoptosis of H9c2 cardiomyocytes remains unclear. In this study, we explored the role of miR-92a-3p in the ethanol-induced apoptosis of H9c2 cardiomyocytes and identified its target genes and signaling pathways. H9c2 cells were cultured with or without 100 mM ethanol for 24 h. The differential expression of miR-92a-3p was verified in H9c2 cells through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To manipulate the expression of miR-92a-3p, both a mimic and an inhibitor were transfected into H9c2 cells. An Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit and apoptosis-related antibodies were used for apoptosis detection through flow cytometry and Western blotting, respectively. Target genes were verified through RT-qPCR, Western blotting, and double luciferase reporter gene assays. miR-92a-3p was significantly overexpressed in ethanol-stimulated H9c2 cardiomyocytes (P < 0.001). After ethanol stimulation, H9c2 myocardial cells exhibited increased apoptosis. The apoptosis rate was higher in the miR-92a-3p mimic group than in the control group. However, the apoptosis rate was lower in the miR-92a-3p inhibitor group than in the control group, indicating that miR-92a-3p promotes the ethanol-induced apoptosis of H9c2 myocardial cells. RT-qPCR and Western blotting revealed that the miR-92a-3p mimic and inhibitor significantly regulated the mRNA and protein expression levels of mitogen- and stress-activated protein kinase 2 and cyclic AMP-responsive element-binding protein 3-like protein 2 (CREB3L2), suggesting that miR-92a-3p promotes the apoptosis of H9c2 cardiomyocytes by inhibiting the MSK2/CREB/Bcl-2 pathway. Therefore, the apoptosis of H9c2 cardiomyocytes increases after ethanol stimulation, and miR-92a-3p can directly target MSK2 and CREB3L2, thereby promoting the ethanol-induced apoptosis of H9c2 myocardial cells.

Morning Glory-Inspired Dual-Function Microcapsules for the Self-Reporting and Self-Healing of Electrothermal-Induced Damage of Electrical Devices.

The long-term operation of power equipment and power electronics can cause local overheating and discharges in the insulation material, resulting in irreversible insulation damage. Further development of such damage can eventually lead to equipment failure, but this problem is very difficult to solve. In this paper, inspired by how the petals of morning glory change color with the environment due to the presence of pigmented globules, a dual-function heat alert in the form of a self-healing (HASH) microcapsule with a nested structure is prepared by using microfluidic technology. By combination of the microcapsule with the insulation material, the local overheating in equipment can be detected promptly under live operating conditions without manual external intervention, and the defects that occur can be repaired autonomously. These HASH microcapsules can be pre-embedded in places at which the material is prone to overheating using artificial magnetic targeting. The doping of the matrix material with microcapsules does not cause any deterioration in its electrical or mechanical properties. This technology is expected to be applied to electrical equipment and electronic devices to allow for the early detection of local overheating and the autonomous repair of defects, thereby ensuring the safety of the equipment and improving its service life.

Automated abdominal adipose tissue segmentation and volume quantification on longitudinal MRI using 3D convolutional neural networks with multi-contrast inputs.

OBJECTIVE: Increased subcutaneous and visceral adipose tissue (SAT/VAT) volume is associated with risk for cardiometabolic diseases. This work aimed to develop and evaluate automated abdominal SAT/VAT segmentation on longitudinal MRI in adults with overweight/obesity using attention-based competitive dense (ACD) 3D U-Net and 3D nnU-Net with full field-of-view volumetric multi-contrast inputs. MATERIALS AND METHODS: 920 adults with overweight/obesity were scanned twice at multiple 3 T MRI scanners and institutions. The first scan was divided into training/validation/testing sets (n = 646/92/182). The second scan from the subjects in the testing set was used to evaluate the generalizability for longitudinal analysis. Segmentation performance was assessed by measuring Dice scores (DICE-SAT, DICE-VAT), false negatives (FN), and false positives (FP). Volume agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: ACD 3D U-Net achieved rapid (< 4.8 s/subject) segmentation with high DICE-SAT (median ≥ 0.994) and DICE-VAT (median ≥ 0.976), small FN (median ≤ 0.7%), and FP (median ≤ 1.1%). 3D nnU-Net yielded rapid (< 2.5 s/subject) segmentation with similar DICE-SAT (median ≥ 0.992), DICE-VAT (median ≥ 0.979), FN (median ≤ 1.1%) and FP (median ≤ 1.2%). Both models yielded excellent agreement in SAT/VAT volume versus reference measurements (ICC > 0.997) in longitudinal analysis. DISCUSSION: ACD 3D U-Net and 3D nnU-Net can be automated tools to quantify abdominal SAT/VAT volume rapidly, accurately, and longitudinally in adults with overweight/obesity.

Clinical characteristics and prognostic analysis of postoperative recurrence or metastasis of low-risk gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. This study aimed to investigate the clinical characteristics and prognosis of postoperative recurrence or metastasis in patients with low-risk stromal tumors, in order to take individualized postoperative management and treatment for patients with low-risk GISTs with relatively high recurrence. METHODS: We retrospectively analyzed the clinicopathological and follow-up data of patients with GISTs who underwent surgical resection in Nanjing Drum Tower Hospital from March 2010 to December 2021. A total of 282 patients with low-risk GISTs were included, none of whom were treated with imatinib. Univariate and multivariate Cox analysis and survival curves were used to explore the relationship between clinical features and recurrence or metastasis in patients with low-risk GISTs. RESULTS: Of the 282 patients with low-risk GISTs who met inclusion criteria, 14 (4.96%) had recurrence or metastasis. There was a correlation between tumor size, primary site, resection type, Ki67 index, neutrophil lymphocyte ratio (NLR) and CD34 expression and postoperative recurrence or metastasis of GISTs (P < 0.05). Subsequently, multifactorial analysis showed that tumor primary site, tumor size, and Ki67 index were independent risk factors affecting postoperative recurrent or metastasis in patients with low-risk GISTs (P < 0.05). Ultimately, According to Kaplan-Meier analysis, non-gastric primary tumors, larger tumors, and high Ki67 index were significantly associated with poor progression-free survival ( PFS ). CONCLUSIONS: Tumor location, tumor size and Ki-67 were independent risk factors for postoperative recurrence and metastasis in patients with low-risk GISTs. Based on the 2008 modified NIH recurrence risk grading system, combined with the above three factors, it can be used to evaluate the prognosis of patients with low-risk GISTs and provide personalized postoperative review and follow-up management recommendations.

One Avocado per Day as Part of Usual Intake Improves Diet Quality: Exploratory Results from a Randomized Controlled Trial.

Background: Few clinical trials have evaluated diet quality change as a predictor of intervention effectiveness. Objectives: The aim of this study was to examine changes in the Healthy Eating Index (HEI)-2015 after a food-based intervention, and assess the associations between HEI-2015 change and intervention effects on cardiometabolic risk-related outcomes. Methods: The Habitual Diet and Avocado Trial was a 26-wk, multicenter, randomized, controlled parallel-arm study. Participants were 1008 individuals aged ≥25 y with abdominal obesity (females ≥ 35 inches; males ≥ 40 inches). The avocado-supplemented diet group was provided 1 avocado per day, and the habitual diet group maintained their usual diet. Change in diet quality was assessed using the HEI-2015 from a single 24-h recall conducted at 4 time points. Mixed models were used for analysis. Results: The avocado-supplemented diet group had a greater increase in the HEI-2015 (4.74 points; 95% CI: 2.93, 6.55) at 26 wk than the habitual diet group. Compared with the habitual diet group, the avocado-supplemented diet group had greater increases in the following HEI-2015 components from baseline: total vegetables (0.99 points; 95% CI: 0.77, 1.21), fatty acid ratio (2.25 points; 95% CI: 1.74, 2.77), sodium (1.03 points; 95% CI: 0.52, 1.55), refined grains (0.82 points; 95% CI: 0.32, 1.31), and added sugars (0.84 points; 95% CI: 0.49, 1.19). No differences in HEI-2015 improvements were observed by race, ethnicity, study site, body mass index, or age category. In the avocado-supplemented diet compared with the habitual diet group, the HEI-2015 increased in females (6.50 points; 95% CI: 4.39, 8.62) but not in males (0.02 points; 95% CI: -3.44, 3.48). Median HEI-2015 change was not associated with intervention-related changes in cardiometabolic disease risk factors. Conclusions: Intake of 1 avocado per day for 26 wk in adults with abdominal obesity increased adherence to the Dietary Guidelines for Americans. Changes in diet quality did not predict changes in risk factors for cardiometabolic disease.This trial was registered at clinicaltrials.gov as NCT03528031 (https://clinicaltrials.gov/study/NCT03528031).

Effect of cinnamon spice on continuously monitored glycemic response in adults with prediabetes: a 4-week randomized controlled crossover trial.

BACKGROUND: Previous clinical studies showing that cinnamon spice lowers blood glucose concentrations had inconsistent results. OBJECTIVES: To determine the effect of daily cinnamon spice supplementation in an amount commonly used for seasoning on glucose concentrations in adults with obesity and prediabetes. METHODS: Following a 2-wk run-in period of maintaining a low polyphenol/fiber diet, 18 participants with obesity and prediabetes underwent a 10-wk randomized, controlled, double-blind, crossover trial (mean age 51.1 y; mean fasting plasma glucose 102.9 mg/dL). The participants were randomly assigned to take cinnamon (4 g/d) or placebo for 4-wk, followed by a 2-wk washout period, and then crossed over to the other intervention for an additional 4-wk. Glucose changes were measured with continuous glucose monitoring. Oral glucose tolerance testing immediately following ingestion of cinnamon or placebo was performed at 4-time points to assess their acute effects both at the baseline and end of each intervention phase. Digestive symptom logs were obtained daily. RESULTS: There were 694 follow-up days with 66,624 glucose observations. When compared with placebo, 24-h glucose concentrations were significantly lower when cinnamon was administered [mixed-models; effect size (ES) = 0.96; 95 % confidence interval (CI): -2.9, -1.5; P < 0.001]. Similarly, the mean net-area-under-the-curve (netAUC) for glucose was significantly lower than for placebo when cinnamon was given (over 24 h; ES = -0.66; 95 % CI: 2501.7, 5412.1, P = 0.01). Cinnamon supplementation resulted in lower glucose peaks compared with placebo (Δpeak 9.56 ± 9.1 mg/dL compared with 11.73 ± 8.0 mg/dL; ES = -0.57; 95 % CI: 0.8, 3.7, P = 0.027). Glucose-dependent-insulinotropic-polypeptide concentrations increased during oral glucose tolerance testing + cinnamon testing (mixed-models; ES = 0.51; 95 % CI: 1.56, 100.1, P = 0.04), whereas triglyceride concentrations decreased (mixed-models; ES = 0.55; 95 % CI: -16.0, -1.6, P = 0.02). Treatment adherence was excellent in both groups (cinnamon: 97.6 ± 3.4 % compared with placebo: 97.9 ± 3.7 %; ES = -0.15; 95 % CI: -1.8, 0.2, P = 0.5). No differences were found in digestive symptoms (abdominal pain, borborygmi, bloating, excess flatus, and stools/day) between cinnamon and placebo groups. CONCLUSIONS: Cinnamon, a widely available and low-cost supplement, may contribute to better glucose control when added to the diet in people who have obesity-related prediabetes. This trial was registered at clinicaltrials.gov as NCT04342624.

Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality.

INTRODUCTION AND OBJECTIVES: Accumulating evidence has supported that mild elevated total bilirubin exerts antioxidant and anti-inflammatory properties in multiple metabolic diseases. We aimed to explore the association of circulating total bilirubin concentration with non-alcoholic fatty liver disease (NAFLD) risk and all-cause mortality and examine the potential nonlinear relationships between them. MATERIAL AND METHODS: We used nationally representative data from the National Health and Nutrition Examination Survey (NHANES). NAFLD was assessed using the fatty liver index (FLI) and United States fatty liver index (USFLI), respectively. RESULTS: A total of 35 912 and 17 329 participants were included in FLI-NAFLD (case with NAFLD was diagnosed by FLI) and USFLI-NAFLD (case with NAFLD was diagnosed by USFLI) groups, respectively. The mean age of total population was 46.25 years, and 48.51% were male. Compared to participants with lowest quintile of total bilirubin concentration, those with highest quintile had lower risk of NAFLD in both FLI-NAFLD (OR: 0.48, 95% CI: 0.40, 0.59) and USFLI-NAFLD (OR: 0.55, 95% CI: 0.43, 0.70) groups. Compared to participants with lowest quintile of total bilirubin concentration, the association between total bilirubin concentration and all-cause mortality was not significant among those with highest quintile of total bilirubin concentration (HR: 0.89, 95% CI: 0.66, 1.20). The restricted spline curves showed the nonlinear U-shaped association of total bilirubin concentration with NAFLD risk and all-cause mortality. The segmented linear regression analysis showed negative associations between total bilirubin concentration and risk of NAFLD in both FLI-NAFLD (OR: 0.94, 95% CI: 0.93, 0.95) and USFLI-NAFLD (OR: 0.95, 95% CI: 0.93, 0.96) groups when total bilirubin concentration was below the turning point (FLI-NAFLD: 18.81 µmol/L; USFLI-NAFLD: 15.39 µmol/L) and these associations were not significant when total bilirubin concentration was higher than the turning point. Furthermore, all-cause mortality decreased (OR: 0.97, 95%CI: 0.95, 1.00) with increased total bilirubin concentration up to the turning point (11.97 µmol/L), and then all-cause mortality increased with increasing total bilirubin concentration (OR: 1.03, 95%CI: 1.02, 1.04). CONCLUSIONS: We found that higher circulating total bilirubin concentration within the physiological range was associated with decreased risk of NAFLD and all-cause mortality among NAFLD patients.

Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy.

Inflammation is a fundamental defensive response to harmful stimuli, but the overactivation of inflammatory responses is associated with most human diseases. Reactive oxygen species (ROS) are a class of chemicals that are generated after the incomplete reduction of molecular oxygen. At moderate levels, ROS function as critical signaling molecules in the modulation of various physiological functions, including inflammatory responses. However, at excessive levels, ROS exert toxic effects and directly oxidize biological macromolecules, such as proteins, nucleic acids and lipids, further exacerbating the development of inflammatory responses and causing various inflammatory diseases. Therefore, designing and manufacturing biomaterials that scavenge ROS has emerged an important approach for restoring ROS homeostasis, limiting inflammatory responses and protecting the host against damage. This review systematically outlines the dynamic balance of ROS production and clearance under physiological conditions. We focus on the mechanisms by which ROS regulate cell signaling proteins and how these cell signaling proteins further affect inflammation. Furthermore, we discuss the use of potential and currently available-biomaterials that scavenge ROS, including agents that were engineered to reduce ROS levels by blocking ROS generation, directly chemically reacting with ROS, or catalytically accelerating ROS clearance, in the treatment of inflammatory diseases. Finally, we evaluate the challenges and prospects for the controlled production and material design of ROS scavenging biomaterials.

Counterintuitive relationship between the triglyceride glucose index and diabetic foot in diabetes patients: A cross-sectional study.

BACKGROUND: Research has shown that insulin resistance (IR) is a known risk factor for diabetic foot (DF), and the triglyceride-glucose (TyG) index is a reliable and simple indicator of IR. However, less is known about the relationship between the TyG and the risk of DF. Here, we investigated the association between the TyG index and the prevalence of DF. METHODS: The eligible records from the Departments of Endocrinology of Shandong Provincial Hospital Affiliated to Shandong First Medical University were screened (from December 1, 2012, to December 31, 2021), and a total of 8866 patients were enrolled. The TyG index was calculated as ln[(fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2)]. The continuous variables between the DF and the non-DF groups were compared by Student's t test or the Mann-Whitney U test, and categorical variables were compared by the chi-square test. Receiver operating characteristic curve (ROC) analysis was carried out to estimate the predictive value of the TyG index for DF. Logistic regression models were used to evaluate the associations between the quartiles of the TyG index and the risk of DF. Subgroup and sensitivity analyses were conducted. RESULTS: The TyG index was significantly lower in the DF group than in the no-DF group. The logistic regression revealed that an increased TyG index was associated with a lower risk of DF after adjusting for potential confounders. In addition, an ROC analysis indicated the discriminatory ability of the TyG index in DF presence with an area under the curve (AUC) of 0.661 (95% CI 0.642-0.680, P < 0.001). Subgroup and sensitivity analysis also supported these robust results. CONCLUSIONS: The TyG index was inversely and dose-dependently associated with the risk of DF in diabetes patients, indicating that elevated TyG index was a protective factor for DF. Future studies are therefore warranted to confirm our finding and to explore the detailed pathological mechanism involved in this process.

Concentrated Grape Powder Consumption Modulates Cholesterol Metabolism and Homeostasis in Healthy Subjects.

SCOPE: Four weeks' of concentrated grape powder (GP) consumption reduces circulating cholesterol in healthy free-living subjects consuming a low-fiber/low-polyphenol diet. Here, the study aims to investigate the underlying mechanisms for cholesterol reduction by evaluating biomarkers of cholesterol de novo biosynthesis, intestinal absorption, miRNA involved in transcriptional regulation of cholesterol metabolism, as well as cholesterol oxidation. METHODS AND RESULTS: Fasting plasma samples collected from 19 healthy free-living subjects at baseline and week 4 of GP consumption are used in this study. Gas chromatography-mass (GC-MS) analysis of plasma samples shows that lathosterol, a precursor of cholesterol synthesis, is significantly decreased after GP consumption indicating reduced cholesterol de novo biosynthesis. Markers of intestinal absorption, campesterol, and ß-sitosterol are not changed. Realtime PCR shows that plasma exosomal miRNA-1 is increased after GP consumption. GC-MS also shows that GP consumption reduces the plasma cholesterol oxidation product 27-hydroxycholesterol (27-HC). CONCLUSIONS: This study enhances the understanding of the mechanisms of the cholesterol lowering effects of GP, and provides new insights into the potential health benefits of grape consumption.

Relationship between dyslipidemia and diabetic retinopathy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Diabetic retinopathy (DR) affects more than 80% of patients with diabetes. However, literature on the association between serum lipids and DR in patients with type 2 diabetes mellitus (T2DM) is inconsistent. Hence, in this study, we aimed to investigate the relationship between baseline serum lipids and the incidence of DR in patients with T2DM. METHODS: We searched relevant articles in the PubMed, Embase databases, and the Cochrane Library up to February 7, 2022, and reviewed the reference lists of the included articles to identify appropriate cohort studies. The weighted mean difference (WMD) and the corresponding 95% confidence intervals (CIs) were calculated. RESULTS: Thirteen cohort studies, including 7459 participants, were included in the present study. Higher levels of total cholesterol (2.94 mg/dL, 95% CI 1.32, 4.56), triglycerides (8.13 mg/dL, 95% CI 5.59, 10.66), and low-density lipoprotein cholesterol (2.53 mg/dL, 95% CI 1.02, 4.04) at baseline were observed in patients with later onset of DR. However, no significant difference in the high-density lipoprotein cholesterol level (0.27 mg/dL, 95% CI - 0.91, 1.45) was observed between patients with DR and without DR. CONCLUSION: The present results suggest that baseline triglyceride and cholesterol levels are significantly associated with the occurrence of DR in patients with T2DM. Thus, patients with T2DM may benefit from lowering serum lipids. Future studies exploring the relationship between longitudinal changes in serum lipids and DR occurrence are warranted. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022319978.

Perspective: Challenges and Future Directions in Clinical Research with Nuts and Berries.

Consumption of nuts and berries are considered part of a healthy eating pattern. Nuts and berries contain a complex nutrient profile consisting of essential vitamins and minerals, fiber, polyunsaturated fatty acids, and phenolics in quantities that improve physiological outcomes. The spectrum of health outcomes that may be impacted by the consumptions of nuts and berries includes cardiovascular, gut microbiome, and cognitive, among others. Recently, new insights regarding the bioactive compounds found in both nuts and berries have reinforced their role for use in precision nutrition efforts. However, challenges exist that can affect the generalizability of outcomes from clinical studies, including inconsistency in study designs, homogeneity of test populations, variability in test products and control foods, and assessing realistic portion sizes. Future research centered on precision nutrition and multi-omics technologies will yield new insights. These and other topics such as funding streams and perceived risk-of-bias were explored at an international nutrition conference focused on the role of nuts and berries in clinical nutrition. Successes, challenges, and future directions with these foods are presented here.

Micronutrient deficiencies in patients with gastrointestinal cancer: To treat or not to treat.

Nutrition supplements are widely used among patients with cancer. The general public perceives supplements as more natural anticancer and antitoxicity agents, and often supplements are used without the knowledge of the treating physician. In the clinical setting, there are concerns that supplements may decrease effectiveness of chemotherapy and/or radiotherapy and, as a result, supplementation is avoided. There is a body of literature evaluating micronutrient deficiencies, supplementation, and cancer risk; however, little is known about the risks of treatment of micronutrient deficiencies in specific cancers. Of the types of cancers, patients with gastrointestinal cancers are at high risk of developing malnutrition and, subsequently, possible micronutrient deficiencies. This review aims to evaluate the effects of supplementation of specific micronutrients in patients with cancer of the digestive tract.

Pea Starch-Lauric Acid Complex Alleviates Dextran Sulfate Sodium-Induced Colitis in C57BL/6J Mice.

The previous documentation has shown the role of resistant starch in promoting intestinal health, while the effect of starch-lipid complex (RS5) on colitis remains unclear. This study aimed to investigate the effect and potential mechanism of RS5 in colitis. We prepared RS5 complexes by combining pea starch with lauric acid. Mice with dextran sulfate sodium-induced colitis were treated with either RS5 (3.25 g/kg) or normal saline (10 mL/kg) for seven days, and the effects of pea starch-lauric acid complex on mice were observed. The RS5 treatment significantly attenuated weight loss, splenomegaly, colon shortening, and pathological damage in mice with colitis. Compare with the DSS group, cytokines levels, such as tumor necrosis factor-α and interleukin-6 in both serum and colon tissue was significantly decreased in RS5 treatment group, while the gene expression of interleukin-10 and the expression of mucin 2, zonula occludens-1, Occludin, and claudin-1 in the colon was significantly upregulated in RS5 treatment group. In addition, RS5 treatment altered the gut microbiota structure of colitis mice by increasing the abundance of Bacteroides and decreasing Turicibacter, Oscillospira, Odoribacter, and Akkermansia. The dietary composition could be exploited to manage colitis by attenuating inflammation, restoring the intestinal barrier, and regulating gut microbiota.

Cell-autonomous effect of cardiomyocyte branched-chain amino acid catabolism in heart failure in mice.

Parallel to major changes in fatty acid and glucose metabolism, defect in branched-chain amino acid (BCAA) catabolism has also been recognized as a metabolic hallmark and potential therapeutic target for heart failure. However, BCAA catabolic enzymes are ubiquitously expressed in all cell types and a systemic BCAA catabolic defect is also manifested in metabolic disorder associated with obesity and diabetes. Therefore, it remains to be determined the cell-autonomous impact of BCAA catabolic defect in cardiomyocytes in intact hearts independent from its potential global effects. In this study, we developed two mouse models. One is cardiomyocyte and temporal-specific inactivation of the E1α subunit (BCKDHA-cKO) of the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, which blocks BCAA catabolism. Another model is cardiomyocyte specific inactivation of the BCKDH kinase (BCKDK-cKO), which promotes BCAA catabolism by constitutively activating BCKDH activity in adult cardiomyocytes. Functional and molecular characterizations showed E1α inactivation in cardiomyocytes was sufficient to induce loss of cardiac function, systolic chamber dilation and pathological transcriptome reprogramming. On the other hand, inactivation of BCKDK in intact heart does not have an impact on baseline cardiac function or cardiac dysfunction under pressure overload. Our results for the first time established the cardiomyocyte cell autonomous role of BCAA catabolism in cardiac physiology. These mouse lines will serve as valuable model systems to investigate the underlying mechanisms of BCAA catabolic defect induced heart failure and to provide potential insights for BCAA targeted therapy.

Microbial changes from bariatric surgery alters glucose-dependent insulinotropic polypeptide and prevents fatty liver disease.

Bariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes.

Mixed Nuts as Healthy Snacks: Effect on Tryptophan Metabolism and Cardiovascular Risk Factors.

We recently demonstrated that the consumption of mixed tree nuts (MTNs) during caloric restriction decreased cardiovascular risk factors and increased satiety. Tryptophan (Trp) metabolism has been indicated as a factor in cardiovascular disease. Here, we investigated the effect of MTNs on Trp metabolism and the link to cardiovascular risk markers. Plasma and stool were collected from 95 overweight individuals who consumed either MTNs (or pretzels) daily as part of a hypocaloric weight loss diet for 12 weeks followed by an isocaloric weight maintenance program for an additional 12 weeks. Plasma and fecal samples were evaluated for Trp metabolites by LC-MS and for gut microbiota by 16S rRNA sequencing. Trp-kynurenine metabolism was reduced only in the MTNs group during weight loss (baseline vs. week 12). Changes in Trp-serotonin (week 24) and Trp-indole (week 12) metabolism from baseline were increased in the MTNs group compared to the pretzel group. Intergroup analysis between MTN and pretzel groups does not identify significant microbial changes as indicated by alpha diversity and beta diversity. Changes in the relative abundance of genus Paludicola during intervention are statistically different between the MTNs and pretzel group with p < 0.001 (q = 0.07). Our findings suggest that consumption of MTNs affects Trp host and microbial metabolism in overweight and obese subjects.

Perspective: A Comprehensive Evaluation of Data Quality in Nutrient Databases.

Nutrient databases are a critical component of nutrition science and the basis of exciting new research in precision nutrition (PN). To identify the most critical components needed for improvement of nutrient databases, food composition data were analyzed for quality, with completeness being the most important measure, and for FAIRness, how well the data conformed with the data science criteria of findable, accessible, interoperable, and reusable (FAIR). Databases were judged complete if they provided data for all 15 nutrition fact panel (NFP) nutrient measures and all 40 National Academies of Sciences, Engineering, and Medicine (NASEM) essential nutrient measures for each food listed. Using the gold standard the USDA standard reference (SR) Legacy database as surrogate, it was found that SR Legacy data were not complete for either NFP or NASEM nutrient measures. In addition, phytonutrient measures in the 4 USDA Special Interest Databases were incomplete. To evaluate data FAIRness, a set of 175 food and nutrient data sources were collected from worldwide. Many opportunities were identified for improving data FAIRness, including creating persistent URLs, prioritizing usable data storage formats, providing Globally Unique Identifiers for all foods and nutrients, and implementing citation standards. This review demonstrates that despite important contributions from the USDA and others, food and nutrient databases in their current forms do not yet provide truly comprehensive food composition data. We propose that to enhance the quality and usage of food and nutrient composition data for research scientists and those fashioning various PN tools, the field of nutrition science must step out of its historical comfort zone and improve the foundational nutrient databases used in research by incorporating data science principles, the most central being data quality and data FAIRness.

Obesity among Asian American people in the United States: A review.

Standard measures of obesity, i.e., body weight and BMI, suggest that Asian American people have a lower obesity prevalence than other racial groups in the United States. However, Asian American people face a unique challenge in their pattern of adiposity with central obesity, which raises the risk for multiple comorbidities, such as type 2 diabetes, metabolic syndrome, and cardiovascular disease, at a lower BMI compared with other populations. Several organizations recommend lower BMI cutoffs for obesity in Asian people (BMI ≥25.0 or ≥27.5 kg/m2 ) instead of the standard ≥30.0 kg/m2 threshold. The risks of obesity and related comorbidities in this population are further influenced by diet, physical activity, perceptions of health, and access to information and therapies. Asian-specific parameters for assessing obesity should become a standard part of clinical practice. Asian American people should equally be offered subgroup-specific tailored interventions owing to heterogeneity of this population. Access to medications and surgery should be improved, in part by updating US indications for therapies to reflect race-specific obesity thresholds and through inclusion of Asian American people of all subtypes with lower BMI values in clinical trials.

Improved outcomes in rheumatoid arthritis with obesity after a weight loss intervention: randomized trial.

OBJECTIVE: To examine whether a weight loss intervention programme improves RA disease activity and/or musculoskeletal ultrasound synovitis measures in obese RA patients. METHODS: We conducted a proof-of-concept, 12-week, single-blind, randomized controlled trial of obese RA patients (BMI ≥ 30) with 28-joint DAS (DAS28) ≥ 3.2 and with evidence of power Doppler synovitis. Forty patients were randomized to the diet intervention (n = 20) or control group (n = 20). Diet intervention consisted of a hypocaloric diet of 1000-1500 kcal/day and high protein meal replacements. Co-primary outcomes included change in DAS28 and power Doppler ultrasound (PDUS)-34. Clinical disease activity, imaging, biomarkers, adipokines and patient-reported outcomes were monitored throughout the trial. Recruitment terminated early. All analyses were based on intent-to-treat for a significance level of 0.05. RESULTS: The diet intervention group lost an average 9.5 kg/patient, while the control group lost 0.5 kg (P < 0.001). Routine Assessment of Patient Index Data 3 (RAPID3) improved, serum leptin decreased and serum adiponectin increased significantly within the diet group and between the groups (all P < 0.03). DAS28 decreased, 5.2 to 4.2, within the diet group (P < 0.001; -0.51 [95% CI -1.01, 0.00], P = 0.056, between groups). HAQ-Disability Index (HAQ-DI) improved significantly within the diet group (P < 0.04; P = 0.065 between group). Ultrasound measures and the multi-biomarker disease activity score did not differ between groups (PDUS-34 -2.0 [95% CI -7.00, 3.1], P = 0.46 between groups). CONCLUSION: Obese RA patients on the diet intervention achieved weight loss. There were significant between group improvements for RAPID3, adiponectin and leptin levels, and positive trends for DAS28 and HAQ-DI. Longer-term, larger weight loss studies are needed to validate these findings, and will allow for further investigative work to improve the clinical management of obese RA patients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02881307.