bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D status and anthropometric measurements of children with Juvenile Idiopathic Arthritis compared to healthy children using the Canadian Health Measures Survey
Authors: Finch Sarah L , Rezaei Elham L , Whiting Susan J , Rosenberg Alan M , Vatanparast Hassan
Published: November 2023

Background

Nutritional impairment can be a factor that contributes to reduced growth in children with Juvenile Idiopathic Arthritis (JIA). One nutrient that might influence growth and be considered in the management of JIA is vitamin D.

Objective

To evaluate vitamin D status and growth parameters in children with JIA compared to healthy children.

Methods

Data from the Canadian multicenter Biologically Based Outcome Predictors (BBOP) study in JIA (n=136) and the Canadian Health Measures Survey (CHMS, n=3,201,735) were used. BBOP data from children, aged 6–16 years with new onset JIA, were compared to age‐matched healthy children from CHMS cycle 1 and 2 for 25(OH)D concentrations, supplement use, milk intake, season of birth, height, weight and BMI z‐scores (age and sex specific). Means and 95% confidence intervals were calculated to determine significance.

Results

Mean 25(OH)D status was significantly higher for JIA patients (79 ± 3.1 nmol/L vs. 68 ± 1.8 nmol/L) who reported use of a supplement with vitamin D more often (50% vs. 7% p <0.05). The prevalence of 25(OH)D deficiency (<30 nmol/L) was 6% for both groups. Children with JIA were more significantly likely to be born in the fall (JIA: 29 ± 3.9 % healthy: 22 ± 1.2 %) and winter (JIA: 33 ± 4.0%, healthy: 24 ± 1.2 %) compared with healthy children who were significantly more likely to be born in the spring (healthy: 27 ± 1.2% JIA: 19 ± 3.4% p<0.05) and summer (healthy: 27 ± 1.5% vs. JIA; 19 ± 3.4%). The proportion of children in each BMI class did not differ between the two groups. Weight and height z‐scores were significantly higher in healthy children (weight: 0.57 ± 0.05 vs −0.12 ± 0.16, height: 0.31 ± 0.04 vs. −0.11 ± 0.10). Daily milk intake was associated with a significantly higher 25(OH)D status (JIA: 86 ± 5.0 nmol/L vs. 70 ±1.8 nmol/L, healthy: 74 ± 5.2 nmol/L vs. 60 ± 2.3 nmol/L).

Conclusion

Children with JIA are shorter and weigh less than healthy children. Vitamin D, which was adequate in the JIA population, is not likely to be a factor accounting for impeded growth. Season of birth may reflect vitamin D status in utero or during the first few months of life. Further research into what role vitamin D status plays in the development and progression of JIA is required.

Support or Funding Information

Funding provided by the Children's Hospital Foundation of Saskatchewan http://medicine.usask.ca/BBOPStudyTeam.pdf
Vitamin C and Zinc Concentrations are Associated with Lower Risk of Inflammation in a School‐aged Population of Children in Rural Mexico
Authors: Garcia Olga P , Torres Karen , Zavala Gerardo A , Camacho Mariela , Ronquillo Dolores , Rosado Jorge L
Published: November 2023

Micronutrient deficiencies may contribute to the inflammatory processes observed in obesity. The relationship between serum micronutrients and inflammatory cytokines in school‐aged children is currently unknown. The aim of this cross‐sectional study was to evaluate the relationship of micronutrient concentrations and inflammatory cytokines in 300 school‐aged children (8.02 ± 1.5 y) in a rural area of Querétaro, Mexico. Serum zinc, iron, vitamins A, C, D, and E, inflammatory markers (IL‐6, IL‐10, TNF‐α, CRP, leptin), glucose, lipid profile, and insulin were assessed. Anthropometry measurements (weight, height and waist circumference), body composition (DXA) and blood pressure were also determined. The prevalence of overweight and obesity was 18% and 11%, respectively; a total of 43.1% of the children had excess body fat. The prevalence of zinc deficiency and vitamin D low concentrations were high (15.2% and 77.9%, respectively). Zinc deficiency, and not vitamin D deficiency, increased the risk of elevated concentrations of IL‐6 (OR= 2.57; 95%CI: 1.26, 5.24) and IL‐10 (OR=2.73; 95%CI: 1.33, 5.61, p<0.05). Of all the micronutrients studied, only zinc was associated with reduced risks of having elevated concentrations of IL‐6 (OR=0.96; 95%CI: 0.94,0.98) and IL‐10 (OR=0.97; 0.95,0.99). Data was further analyzed according to the body fat content of the children and if they were overweight/obese or normal weight. The odds of having high concentrations of IL‐6 (OR=0.82; 0.67,0.99) or IL‐10 (OR=0.80; 0.66,0.97) were reduced in children with normal body fat and high vitamin C levels. Overweight and obese children with higher zinc concentrations had reduced odds of elevated IL‐6 (OR=0.90; 95%CI: 0.85, 0.96, p<0.05) and TNF‐α (OR=0.93; 95%CI: 0.88, 0.97 p<0.05). In addition, children with higher zinc concentration that had excess body fat had reduced odds of elevated IL‐6 (OR=0.94; 95%CI: 0.91, 0.98, p<0.05). In conclusion, in this population, higher zinc and vitamin C concentrations are associated with reduced odds of higher concentration of inflammation markers.

Support or Funding Information

Partially funded by INSK
Cranberry Beverage Consumption Reduces Antibiotic Use for Clinical Urinary Tract Infection in Women with a Recent History of Urinary Tract Infection
Authors: Nieman Kristin M , Dicklin Mary R , Schild Arianne L , Kaspar Kerrie L , Khoo Christina , Derrig Linda H , Gupta Kalpana , Maki Kevin C
Published: November 2023

Urinary tract infection (UTI) is one of the most commonly diagnosed types of bacterial infection, and is often treated with antibiotic therapy. Preventive approaches are needed to minimize unnecessary use of antibiotic therapy, which can contribute to the development of antibiotic resistant pathogens. The effect of the consumption of a daily cranberry beverage (240 mL/d; n = 185) compared to a placebo beverage (n = 188) on episodes of clinical UTI was investigated in a 24‐week, randomized, double‐blind, placebo‐controlled, multicenter clinical trial in women with a history of a recent UTI (Am J Clin Nutr 2016;103:1434–42; NCT01776021). The aim of this post‐hoc analysis was to evaluate the effect of consuming the cranberry beverage on the incidence of antibiotic use for treatment of three categories of clinical UTI: investigator‐diagnosed, probable UTI (subject was not examined by the investigator but a non‐study healthcare provider prescribed an antibiotic), and possible UTI (self‐administered antibiotic therapy). Investigator‐diagnosed episodes of clinical UTI were significantly reduced in the cranberry beverage group, relative to placebo (39 vs. 66; incidence rate ratio [IRR]: 0.63; 95% confidence interval [CI]: 0.42, 0.93; P = 0.021). There was a trend for reduced investigator‐diagnosed plus probable episodes of UTI in the cranberry group (47 vs. 71; IRR: 0.70; 95% CI: 0.48, 1.01; P = 0.056). Investigator‐diagnosed plus probable and possible episodes of UTI were significantly reduced in the cranberry group (47 vs. 73; IRR: 0.68; 95% CI: 0.47, 0.98; P = 0.038). The results of this post‐hoc analysis indicate that daily consumption of a cranberry beverage reduced the incidence of antibiotic treated clinical UTI in women with a recent history of UTI.

Support or Funding Information

Funded by Ocean Spray Cranberries, Lakeville‐Middleboro, MA
B cell cytokine secretion and antibody production are impaired upon BCR/TLR9 stimulation in obese subjects
Authors: Kosaraju Rasagna , Guesdon William , Shaikh Saame Raza
Published: November 2023

Obesity is hypothesized to drive an impairment in humoral immunity. However, it is unclear how obesity directly targets B cell responses in humans. This study investigated how obese subjects, relative to lean controls, responded to anti‐B cell receptor (BCR) and toll‐like receptor (TLR) 9 stimulation. Obese individuals with a BMI of >30 had a significant increase in the percentage of B cells in circulation compared to their lean counterparts whereas the percentage of monocytes, helper T cells, and cytotoxic T cells remained unchanged. B cell IL‐6 secretion was lowered upon anti‐BCR/TLR9 stimulation in the obese compared to lean controls. Furthermore, a positive correlation was observed between BMI and IgM, but not IgG, production upon anti‐BCR/TLR9 stimulation. These results demonstrate that B cell function is impaired in obese individuals, which could contribute toward diminished responses to infection and vaccination in obesity.

Support or Funding Information

Research was supported by NIH R01AT008375
Effects of a 6 Week Aerobic Exercise Intervention on Gut Bacterial Metabolites in Lean and Obese Adults
Authors: Mailing Lucy , Allen Jacob , Niemiro Grace , Cohrs Josh , Holscher Hannah , De Lisio Michael , Woods Jeffrey
Published: November 2023

Introduction

Dietary changes have been shown to significantly alter the composition and metabolic function of the gut microbiota in both mice and humans; however, study of the effects of exercise alone on the gut microbiota and microbial metabolites has been limited to mice. Short chain fatty acids (SCFAs) are bacterial metabolites with numerous downstream effects on the host, influencing satiety, inflammation, and adiposity. Here, we characterized the effects of an aerobic exercise intervention on fecal SCFA output in lean and obese humans.

Methods

Previously sedentary but otherwise healthy adults (n=11 lean; n=4 obese) underwent a six week aerobic exercise intervention. Participants performed 3 exercise sessions per week on a bike and/or treadmill, starting with 30 min at 60% HRR and building up to 60 min at 75% HRR by week 6. Fecal samples were collected before and after the intervention, preceded by a 3‐day control diet. Approximately 0.1 g of fecal samples was immediately stabilized in metaphosphoric acid until SCFA analysis by gas chromatography/mass spectrometry (GC/MS).

Results

Six weeks of exercise caused a significant increase in the fecal concentration of butyrate, acetate, and propionate (p<0.01), among lean individuals. The changes in acetate and butyrate concentrations were strongly correlated to changes in lean mass as a result of training, an effect driven by the lean individuals (r=.633 p<0.029 and r=0.854, p<0.01, respectively). However, exercise training failed to increase fecal SCFA concentration in our small sample of obese individuals (p>0.05).

Conclusion

A 6‐week aerobic exercise intervention is sufficient to increase fecal SCFA concentrations in lean, adult humans. This effect was not observed in obese individuals, however, and thus suggests that exercise‐induced metabolic changes within the gut may be influenced by obesity status
Lipid‐Lowering Potential of Combined Phytosterols and Curcumin Supplementation in Hypercholesterolaemic Individuals
Authors: Ferguson Jessica Jayne Anne , Stojanovski Elizabeth , MacDonald‐Wicks Lesley , Garg Manohar Lal
Published: November 2023

Hyperlipidaemia remains one of the major risk factors for the development of cardiovascular disease (CVD). Phytosterols (PS) are well known for their potent cholesterol‐lowering potential, while curcumin has also been shown to possess lipid‐lowering properties.

The aim of this research was to investigate the effects of combined dietary supplementation with PS and curcumin on blood lipid concentrations in hypercholesterolaemic individuals based on a four‐week 2×2 factorial, double‐blinded, randomised, placebo‐controlled trial. Participants received either control (double placebo) or 2 g/d PS or 200 mg/d curcumin or a combination of PS plus curcumin.

Following dietary supplementation with PS, LDL‐cholesterol (LDL‐C) was significantly reduced (−8.1%, p<0.05) compared to the control group. The combined PS plus curcumin treatment lowered plasma total‐ and LDL‐C concentrations (−9.9%, p<0.05 and −13.5%, p<0.05; respectively) more effectively than the curcumin (−2.9% and −3.2% respectively) and control (−1.2% and −0.9% respectively) treatments. Plasma HDL‐C, triglyceride concentrations and total cholesterol/HDL ratio remained unchanged irrespective of the intervention.

This study presents a novel two‐pronged approach to minimise CVD risk in hypercholesterolaemic adults using a unique dietary combination with a clinically significant effect and no adverse side effects by reducing blood cholesterol concentrations and potentially inflammation within a short period of time. These results support the development of functional foods containing the two bioactives as a preventative strategy providing effective drug‐like cardio‐protection.

Support or Funding Information

Not applicable
Replacement of Refined Carbohydrates with a Combination of Egg Protein and Unsaturated Fatty Acids Improves the Lipoprotein Lipid Profile in Adults with Elevated Triglycerides
Authors: Palacios Orsolya M , Maki Kevin C , Nieman Kristin M , Lindner Emily , Huebner Margie , Sorce Jennifer
Published: November 2023

The aim of this trial was to evaluate the effects of a combination of egg protein (Epro) and unsaturated fatty acids (UFA), substituted for refined carbohydrates (CHO), on the lipoprotein lipid profile in adults with elevated triglycerides (TG). This randomized, controlled‐feeding, crossover study included an evaluable sample of 25 men and women with a mean (± SEM) age and body mass index of 46.3 ± 2.4 y and 31.8 ± 1.0 kg/m2, respectively, and a median (interquartile range) baseline TG of 173 mg/dL (159, 228). Subjects consumed a standardized diet that incorporated at least 3 servings/d of test foods (yogurt, muffins, waffles, and cookies), which provided 40–60% of daily energy needs. The study foods accounted for 8% higher protein energy (from Epro) and 8% higher fat energy (from UFA) in the Epro/UFA condition and 16% higher CHO energy in the refined CHO condition. Total energy intake was held constant during each condition; dietary CHO, protein and fat comprised 42%, 23% and 35% of energy intake during the Epro/UFA condition and 58%, 15% and 27% of energy intake during the refined CHO condition. Both the Epro/UFA and the refined CHO diets were low in saturated fatty acids (7.0 ± 0.1% and 6.5 ± 0.1% of energy intakes, respectively). Fasting blood samples were collected at baseline and the end of each condition, and lipid profiles were analyzed using enzymatic colorimetric methodology. Low‐density lipoprotein cholesterol (LDL‐C) concentrations were calculated using the Friedewald equation. The median percent change from the habitual diet at baseline for TG was −18.5% (−35.7%, −6.9%) following the Epro/UFA condition relative to a 2.5% (−13.4%, 17.0%) increase following the refined CHO condition (p < 0.002). The median percent change from baseline in very low‐density lipoprotein cholesterol (VLDL‐C) was −18.6% (−34.8%, −7.4%) following the Epro/UFA condition and −3.6% (−12.5%, 16.2%) following the refined CHO condition (p < 0.002). Both conditions resulted in reductions from baseline in total cholesterol, LDL‐C, non‐high‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol, but there were no significant differences between conditions. In summary, replacement of dietary CHO with a combination of Epro and UFA reduced circulating TG and VLDL‐C levels in adults with elevated TG.

Support or Funding Information

Funded by American Egg Board/Egg Nutrition Center, Park Ridge, IL
Therapeutic Benefits of Glutamine: An Umbrella Review of Meta‐Analyses
Authors: McRae Marc
Published: November 2023

Introduction

Glutamine may become a conditionally essential amino acid in patients with catabolic disease as it has been shown that circulating glutamine levels drop during critical illness and following major surgery and this may result in an increase in secondary infection risk, recovery time and mortality rates. However there is much discrepancy in the literature when it comes to randomized controlled studies and so this umbrella review of published meta‐analysis was performed to examine the effectiveness of glutamine's role as a therapeutic agent.

Methods

A PubMed, Cochrane Library and CINAHL from January 1st, 1980 to September 30th, 2016 was conducted using the following search strategy: “glutamine AND (meta‐analysis OR systematic review)”. Only English language publications were retrieved which provided quantitative statistical analysis on pooled treatment effects on the relative risks and odds ratios of infectious complications, length of stay in hospital and mortality.

Results

Twenty‐one meta‐analyses were entered into this umbrella review. Fifteen of 19 meta‐analyses found statistically significant reductions of infectious complications with relative risks ranging between 0.42 and 0.93. Twelve of 18 meta‐analyses found statistically significant reductions in the length of stay in hospital with reductions ranging between 0.42 to 4.73 days. Only 4 of 15 meta‐analyses found statistically significant reductions in mortality with relative risks ranging between 0.64 and 1.01. Statistically significant heterogeneity was observed in 16 of 22 meta‐analyses, and publication bias was observed in 5 of 11 meta‐analyses.

Conclusion

Glutamine supplementation for critically ill or surgical patients through parenteral or enteral routes appears to reduce the rate of hospital acquired infectious complications and shortening of the length of stay in hospital. Glutamine supplementation also appeared to reduce the rate of in‐patient mortality, but the majority of meta‐analyses did not reach statistical significance. However, we must appreciate the positive results with some caution in light of the fact that there exists statistically significant heterogeneity for the majority of meta‐analyses, and statistically significant publication bias in almost half.

Support or Funding Information

There was no funding for this project.
Moderate/severe acne in adults is associated with a poor diet quality
Authors: Burris Jennifer Christine , Rietkerk William , Shikany James , McConnell Colleen , Woolf Kathleen
Published: November 2023

Increasing evidence suggests a relationship between dietary intake and acne. The 2010 Healthy Eating Index (HEI‐2010) is a measure of diet quality used to determine adherence to dietary guidelines. This study investigated diet quality using the HEI‐2010 among adults with no acne and those with moderate/severe acne. Thirty‐four participants with no acne (22±4 years; n=7 males, n=27 females) and 33 participants with moderate/severe acne (21±2 years; n=11 males, n=22 females) completed a 5‐day food record, body composition assessment, and health history questionnaire. Self‐reported diet and HEI‐2010 scores were analyzed using Nutrition Data System for Research (NDSR). A dermatologist assessed acne severity using digital photographs. There were no significant differences in age, sex, percent body fat, and body mass index (BMI) between groups. Participants with moderate/severe acne had a significantly lower mean (±SD) overall diet quality score (HEI‐2010=53.0±14.7) compared to participants with no acne (HEI‐2010=68.4±15.6) (p<0.001). Participants with moderate/severe acne had significantly lower scores for the vegetables (p=0.008), greens and beans (p=0.003), whole grains (p=0.019), seafood and plant proteins (p=0.004), and refined grains (<0.001) components compared to participants with no acne. There were no differences in the total fruit, whole fruit, total dairy, total protein, fatty acids, total sodium, and empty calorie components between the groups. These results suggest an association between diet quality and acne.
Luteolin inhibits indoxyl sulfate‐induced inflammation through suppression of NF‐kB activation in human endothelial cells
Authors: Chuang Ya‐Chi , Hsu Yi‐Hsuan , Li Chien‐Chun
Published: November 2023

Atherosclerosis is an inflammatory vascular disease frequently associated with chronic kidney disease (CKD). Indoxyl sulfate, one of the uremic toxins, has been shown to stimulate the production of reactive oxygen species, accelerate kidney injury and progression of CKD. In addition, other studies reported that indoxyl sulfate may also be responsible for vascular disease by inducing inflammation in endothelial cells. Luteolin, also known as 3′4′5,7‐hydroxyl flavone, has been reported to have anti‐oxidative and anti‐inflammatory properties. The aim of this study was to investigate the effect ofluteolin on indoxyl sulfate‐mediated inflammatory response in endothelial cells, and the underlying mechanism involved. In this study, the human EA.hy926 cells were incubated with or without luteolinin the presence of indoxyl sulfate. The expression of the intracellular cell adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecules‐1 (VCAM‐1), monocyte chemotactic protein‐1 (MCP‐1) and NF‐kB p65 subunit were determined by Western blotting. Adhesion of HL‐60 cells onto EA.hy926 cells was assessed by cell adhesion assay. The results showed indoxyl sulfate dose‐dependently induced ICAM‐1, VCAM‐1, and MCP‐1 expression, whereas treatment with luteolin suppressed this induction by indoxyl sulfate. We found that 2 μM of luteolin significantly attenuated indoxyl sulfate‐induced adhesion of leukocyte to EA.hy926 cells. Furthermore, luteolin inhibited indoxyl sulfate‐induced nuclear accumulation of p65 and NF‐kB transactivation in EA.hy926 cells. Our results demonstrated that luteolin attenuates indoxyl sulfate‐induced expression of adhesion molecules and chemokines at least partially through suppression of NF‐kB signaling in endothelial cells, suggests that luteolin might has a potential effect against vascular inflammation in patients with CKD.
Dietary Red Raspberry Enhances Intestinal Epithelium Repair in Chronic Colitis
Authors: Bibi Shima , Du Min , Kang Yifei , Sun Xiaofei , Xue Yansong , Moraes Luis Fernando Sousa , Zhu Meijun
Published: November 2023

Introduction

Ulcerative colitis (UC) causes repeated mucosal injuries of the intestinal epithelium, increasing the likelihood of colorectal cancer development. The risk of UC‐associated colorectal cancer increases with increase in wound region and duration of the disease. Dietary nutrients affect the intestinal epithelium repair and wound healing. Red raspberry (RB), a rich source of phytochemicals, has beneficial effects on the acute colitis by reducing inflammation.

Objective

To investigate the effects of RB on intestinal repair mechanisms using dextran sulfate sodium (DSS)‐induced chronic colitis model

Methods

Six‐week‐old wild‐type male mice were fed with a standard rodent diet supplemented with RB (0 or 5% of dry feed weight) for 10‐weeks. At 4th week of the dietary treatment, mice were subjected to two repeated cycles of 1% DSS induction. Each cycle was consisted of 7 days of 1% DSS treatment and 14 days of recovery (removing the DSS from their drinking water). Mice were monitored on daily basis for disease symptom throughout the DSS‐treatment and recovery period. Colonic tissues were collected at the end of the study.

Results

There was no difference in feed and water consumption among the treated groups throughout the study. All the mice survived during DSS‐treatment and recovery period. RB supplementation decreased body weight, improved the disease activity index, and colon epithelium repair and wound healing in DSS‐induced mice. In addition, RB supplementation decreased cyclooxygenase‐2 (COX‐2) and interleukin (IL)‐6 protein content, and decreased CD4 T‐cell infiltration in the colon. Furthermore, RB supplementation enhanced the content of differentiation markers, Hairy/Enhancer of Split 1 (HES 1), E‐cadherin, while reduced mucin (MUC)‐1 and β‐catenin contents.

Conclusion

RB supplementation suppressed inflammation and facilitated epithelium repair in DSS‐induced chronic colitis (NATL PROC RASPBERRY CNCL)

Support or Funding Information

(NATL PROC RASPBERRY CNCL)
Phenolic profiles and antioxidant abilities of various extracts from white maitake mushrooms (Grifola frondosa)
Authors: Chen Hsiao‐ling , Wang Ya‐Chien , Lin Chien‐Yih
Published: November 2023

Maitake (Grifola frondosa), a basidiomycete fungus belonging to the Polyporaceae family is consumed as a valuable mushroom in the Asia. Extensive studies focus on the anti‐carcinogenic and immune‐modulatory aspects of the polysaccharide fractions, such as maitake D (MD) and X fractions, that are isolated from a boiling water extract of grey fruiting bodies. However, the non‐polysaccharide bioactive compounds, especially the phenolic compounds, are rarely studied in the maitake mushroom and never studied in the white maitake. The white maitake fruiting body was extracted with 50% ethanol (v/v) and cold water into fractions (F) 1 and 2, respectively. The F2 was further extracted with 75% ethanol (v/v) to remove the polysaccharide, and the soluble fraction was denoted as fraction 3. All fractions were lyophilized for further analysis including the DPPH scavenging ability, total polyphenol, flavonoid and the individual phenolic compound content. Results indicated that the white maitake contained a large amount, 62% w/w, of cold‐water soluble material. The DPPH scavenging effect was F3>F2>>F1as the concentration was equal or greater than 0.4 mg/mL. At 1.2 mg/mL, the DPPH scavenging effect of F3 was almost equal to that of ascorbic acid. The F2 and F3 contained much more total polyphenol and flavonoid than F1. The major phenolic compounds identified were tannic and gallic acids. The F1–3 contained (mg/g extract) 1.33 ± 0.01, 12.33 ± 0.42 and 13.33 ± 0.32 of tannic acid, and 0.43 ± 0.02, 5.68 ± 0.12, and 6.45 ± 0.32 of galllic acid. The antioxidant ability was strongly and positively correlated with the total polyphenol, flavonoid, tannic, and gallic acid content, respectively. Therefore, this study suggests that cold water extract of white maitake exhibited strong DPPH scavenging effect, which was likely to be mainly contributed by tannic and gallic acids.
Characterization of the immunomodulatory compound derived from beta‐lactoglobulin via Maillard reaction
Authors: Chun Su‐Hyun , Lee Kwang‐Won
Published: November 2023

Beta‐lactoglobulin (BLG) is the major compound more than 50% of whey protein. Although it has high contents of the essential amino acids and functional properties, its application of ingredient in food manufacturing is limited due to its allergenicity. Recently, to increase the application in food industry, research of the reducing the allergenicity was reported the methods such as chemical modification, heating, or proteolysis. There are several reports that Maillard reaction improves the functional properties of protein. In this research, we prepared BLG which has reduced allergenicity by removing endotoxin, derived Escherichia coli. The BLG was glycated with lactose under the condition at 55°C for 24 h. To identify the immunomodulatory compounds derived BLG, glycated BLG was applied to the sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, and the separated bands were digested using the method of in‐gel trypsin digestion. The peptide sequence of the immunomodulatory compound was obtained by the results of a matrix‐assisted laser desorption/ionization coupled with time‐of‐flight tandem mass spectrometer (MALDI‐TOF‐MS) analysis. On the result of this research, we found that the immunomodulatory effect of BLG was observed in the active compound derived BLG via Maillard reaction. Therefore, we suggested that glycated BLG could be an immunomodulatory material in the foods.
The intake of xylobiose containing sugar mixture improves the defecation frequency and symptoms in young women with chronic constipation
Authors: Kim Arm , Kim(a) Hye Young , Lee Jung Sug , Kyung Myungok , Chang Moon Jeong
Published: November 2023

We investigated the effects of the intake of xylobiose containing sugar mixture(XBS) in the defecation frequency and bowel symptoms in young women (mean age of 22.6 years old) with chronic constipation. Fifteen subjects were treated with 10 gram of sugar containing 7% xylobiose daily for 8 weeks. During the experimental period, the clinical efficacy was evaluated by a daily self‐administered questionnaire survey including the number of stools and the clinical symptoms score. The mean frequency of defecations were 2.31in the pretreatment week and increased significantly to 3.47, 3.67, 3.73, 3.67, 4.00, 3.73,3.87 and 4.27 in weeks of 2 to 8 of XBS intake. The total constipation symptom score was 10.53 initially and significantly decreased to 6.92 at final week. At the end of the study the occurrence of very hard stools and hard stools decreased and the stool consistency normalized. XBS intake significantly alleviated the abdominal displeasure and bloating in weeks 6,7, and 8 (p<0.05). The transition time of evacuation of stool was significantly different in week of 5, 7, and 8 (p<0.05). Side effects were not reported. Our results suggest that he intake of XBS was effective for the alleviation of clinical symptoms related with constipation in young women in this study. This study was approved by the IRB at Kookmin University, Seoul, Republic of Korea.

Support or Funding Information

This research was supported by High Value added Food Technology Development Program 2016, Ministry for Food, Agriculture, Forestry, Republic of Korea
Behaviour Change Counselling: Training Graduate Dietetic Students in Shortened Motivational Interviewing
Authors: Hagedorn Rebecca L , Barr Makenzie L , Famodu Oluremi A , Clark Rashel L , Morris Allison M , Wattick Rachel A , Waanders Timothy R , Olfert Melissa Diann
Published: November 2023

Motivational interviewing is a client centered approach that works to elicit behaviour change from within. A shortened method, Behavior Change Counseling, is often used in lifestyle changes in the clinical setting. For this study, graduate dietetic students were counselors as part of a fruit and vegetable intervention and were assessed for adherence to behavior change counseling. The counselors (n=5) were doctoral students in dietetics at West Virginia University and n=2 hold registered dietitian (RD) licensure. Counselors were female with average counseling experience of one year (0.8±1.3), with two counselors having no previous counseling experience. Each counselor was assigned intervention participants to counsel based on schedule, with each counselor having at least one participant and no more than 10 participants. Counselors were first trained across two consecutive days on motivational interviewing techniques by a member of the Motivational Interviewing Network of Trainers (MINT). Training tactics included lecture, role play and teach backs. Following training, counselors completed the 8‐week fruit and vegetable intervention where they met with subjects weekly. Counseling sessions were audio recorded with permission from subjects. To measure adherence and improvements in behavior change counseling, baseline (week 2) and post (week 8), audio tapes were randomly selected and coded using the Behaviour Change Counselling Index (BECCI) by three independent raters. BECCI contains eleven, five‐point Likert‐scaled items that ranks counselor's motivational interviewing techniques (0‐not at all, 1‐minimally, 2‐to some extent, 3‐a good deal, 4‐a great extent). All raters underwent a brief training on motivational interviewing and watched a training video on health behaviour change. The raters completed one counselling session together to ensure reliability between raters, with results showing interrater reliability .20 points of one another. Results showed that on average counselors used motivational interviewing techniques a good deal of the time at baseline (t0=2.71) and improved slightly to post (t1=2.75) yet did not reach significant improvements for overall score (p=0.87). Counselors with limited counseling experience at baseline showed greater improvements over time (t0=2.63; t1=2.83; p=0.29). These findings indicate that graduate dietetic students were already using motivational interviewing techniques as part of their counseling sessions but did show slight improvements, especially in those with low counseling experience.

Support or Funding Information

Approval to use the data set was granted by the University of West Virginia University Institutional Review Board prior to study implementation.
Purine Metabolism and Barrier Formation in Intestinal Epithelial Cells
Authors: Lee J Scott , Colgan Sean P
Published: November 2023

Loss of epithelial barrier function is a hallmark in the pathogenesis of inflammatory bowel disease (IBD). Active inflammatory responses in the mucosa are characterized by fundamental shifts in energy supply and demand, although such metabolic changes are incompletely understood. Guided by an unbiased metabolomic screen of colonic tissue from healthy and actively colitic mice, we identified broad depletion of purine metabolites and cellular initiation of the energetically costly de novo synthesis of purines in response to metabolite loss. As barrier function is known to require high cellular energy, we pursued the hypothesis that protection against purine depletion will promote barrier function, with selective purine metabolites serving as predictable biomarkers of successful barrier formation. For these purposes, we profiled purine metabolism during the formation of intestinal epithelial barrier in vitro. These studies revealed that limiting purine loss through creatine supplementation enhanced barrier formation – a “top‐down” protection by increasing the phosphocreatine pool to limit ATP degradation. Additionally, we observed that hypoxanthine positively correlated with the magnitude and kinetics of barrier formation. As hypoxanthine‐guanine phosphoribosyltransferase (HGPRT) utilizes hypoxanthine in the first step of the purine salvage pathway, hypoxanthine may protect against purine degradation from the “bottom‐up.” Further studies with hypoxanthine and allopurinol (to inhibit hypoxanthine degradation by xanthine oxidase) supplementations supported the hypothesis by enhancing barrier, implicating the significance of purine salvage in barrier function. These findings are in agreement with the strategies employed by intestinal epithelial cells to preserve purine metabolites upon inflammatory insult and represent a potential therapeutic approach for the treatment of IBD.
Insulin alters brain lipid profile and mitochondrial function
Authors: Carr Sheryl , Trumbull Annie , Hutchinson BreAnna , Dallon Blake , Harrison Mitchell , Gray Harrison , Gibbs Jonathan , Eskildsen Dane , Kudlacek Jess , Heldt Brett , Clayton Craig , Wisco Jonathan J. , Bikman Benjamin T.
Published: November 2023

Alzheimer's disease (AD), the most common neurodegenerative disorder worldwide, is characterized by increased levels of neurofibrillary tangles and amyloid‐beta plaques. Evidence has previously implicated the potent role that insulin resistance plays in the development and progression of AD, suggesting to some that AD represents a distinct type of diabetes. Additionally, disparate lines of evidence find a role for alterations in brain mitochondrial function in AD etiology. We sought to test a unifying hypothesis—namely, that hyperinsulinemia promotes accrual of the sphingolipid ceramide, which, as we've previously found, pathologically alters mitochondrial function. Via daily insulin injections, we induced hyperinsulinemia in ApoE4 mice. In addition to insulin, one group received myriocin injections to inhibit ceramide biosynthesis. We observed significant increases in brain ceramides in the insulin‐treated group, which correlated with disrupted brain mitochondrial function. However, the group receiving myriocin alone, or, importantly, myriocin with insulin had normal lipid profiles and apparently normal mitochondrial bioenergetics. Altogether, our findings suggest a causative role for insulin in AD etiology via an insulin‐induced upregulation of ceramide biosynthesis and accrual in the brain.
The Role of Cystathionine Gamma Lyase and Endothelial Nitric Oxide Synthase for Cardiovascular Homeostasis
Authors: Al Shaarani Majd , Green Jonette , Traylor James , Bhuiyan Md Shenuarin , Orr A Wayne , Kevil Christopher G
Published: November 2023

Nitric oxide (NO) and hydrogen sulfide (H2S) are two important vasoactive gasotransmitters. Both NO and H2S are essential in the genesis, development, repair and remodeling of blood vessels. They also have a cardio‐protective role that stems from their ability to regulate vasodilation, blood pressure and and the growth of new blood vessels. Genetic deficiency of either endothelial NO synthase (eNOS) or Cystathionine γ‐lyase (CSE, one of the genes implicated in H2S synthesis) has detrimental effects on tissue vascularization and vascular repair against shear forces and atherosclerotic changes. While the deletion of either gene alone has been previously studied; the effects of genetic deficiency of both genes together in the same animal has not been previously evaluated. In this study, we report that when both genes are deleted severe cardiovascular pathological changes emerge. Cardiac ejection fraction (EF) and fraction shortening (FS) measured on 2D/M mode echocardiogram performed on homozygous eNOS/CSE double knockout mice was severely diminished compared to that of homozygous CSE null/heterozygous eNOS knockout mice. H&E stained sections of the aorta showed significant changes with irregular, eosinophilic and less defined elastic laminae with loss of refractility and edematous tunica media with pauci‐cellularity and hypochromatic nuclei. These data are the first to reveal a critical relationship between eNOS and CSE expression for basal cardiac function and tissue histological organization.

Support or Funding Information

This work supported by HL113303
ENaC‐a mediates the protective effect of the TNF‐derived TIP peptide in pneumolysin‐induced capillary barrier dysfunction
Authors: Czikora Istvan , Sridhar Supriya , Alli Abdel , Verin Alexander , Chakraborty Trinad , Fulton David , Eaton Douglas C , Lucas Rudolf
Published: November 2023

Background

Streptococcus pneumoniae is the major etiologic agent of bacterial pneumonia. Autolysis and antibiotic‐mediated lysis of pneumococci releases the pore‐forming toxin, pneumolysin (PLY), which is the primary cause of acute lung injury. PLY unleashes the perfect storm, by inhibiting alveolar liquid clearance (ALC) and by potently compromising alveolar‐capillary barrier function, which together cause potentially lethal permeability edema associated with pneumonia. As a consequence, alveolar flooding occurs, which can precipitate lethal hypoxemia by impairing gas exchange. Apart from being the entry step in Na+ reabsorption across Na+‐transporting epithelia, the epithelial sodium channel (ENaC) was recently suggested to affect stiffness in the large vasculature, but its role in barrier function in the microvasculature has not been investigated so far. In this study, we therefore investigated the consequences of specific ENaC activation or depletion on capillary barrier function, in the presence or absence of PLY.

Methods

Expression of α, β and γ subunits of ENaC and protein phosphorylation status in HL‐MVEC were assessed in Western blotting. Barrier function in untreated and PLY‐treated human lung microvascular endothelial cell (HL‐MVEC) monolayers was monitored using electrical cell‐substrate impedance sensing (ECIS). In order to investigate the role of ENaC in barrier function in HL‐MVEC, we either activated the channel, using the TNF‐derived TIP peptide, which directly binds to the α subunit, or we depleted the crucial ENaC‐α subunit with specific siRNA.

Results

HL‐MVEC express all three subunits of ENaC. TIP peptide‐mediated ENaC activation significantly strengthened barrier function in PLY‐treated HL‐MVEC. By contrast, ENaC‐α depletion significantly increased sensitivity to PLY‐induced hyperpermeability and blunted the protective effect of the TIP peptide. PLY significantly increased phosphorylation of the actin‐binding protein filamin A, which was shown to directly bind to ENaC‐α and which promotes the interaction between ENaC with MARCKS, an important mechanism for activation of the channel's open probability. TIP peptide‐mediated activation of ENaC blunted phosphorylation of both calmodulin dependent Kinase II (CaMKII) and its substrate filamin A.

Conclusions

Taken together, our results demonstrate a previously unrecognized role for ENaC, and more specifically for ENaC‐α, in strengthening barrier function of human lung capillaries. As such, these data suggest that strategies aiming to activate ENaC have the potential to not only improve ALC in the alveolar epithelium, but also barrier function in the capillary endothelium during pneumonia.
Epigenetic Regulation of Stab2 Expression in DBA Mice in Determining Atherosclerosis Susceptibility
Authors: Dong Sharlene , Kayashima Yukako , Maeda Nobuyo
Published: November 2023

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in the large arteries that often leads to acute occlusion and myocardial infarction. The aortic arch and root are two regions with distinct patterns of lesion development in a mouse model of atherosclerosis. A quantitative trait locus (QTL) analysis of the F2 generation from an intercross between ApoE‐null mice on 129S6 and DBA/2J backgrounds has revealed a significant locus on chromosome 10, Aath5, that affects plaque size in the aortic arch. The DBA allele of Aath5 confers resistance to aortic arch atherosclerosis. One candidate gene in the Aath5 locus is the Stab2 gene, which encodes a receptor for hyaluronan. The DBA allele of Stab2 was found to be associated with ten‐fold levels of plasma hyaluronan in DBA mice compared to 129 mice. The DBA allele of the Stab2 gene also includes a unique intracisternal A‐particle (IAP) retrotransposon inserted in a reverse orientation in the promoter region, driving the Stab2 expression from its long‐terminal repeat sequence (5′ LTR). Methylation status of the LTR of the IAP sequence was analyzed through allele‐specific bisulfite sequencing and found to be correlated with ectopic expression in the heart, aorta, macrophages and kidneys. Thus, epigenetic regulation of this IAP element may play a role in regulating Stab2 expression and possibly affect atherosclerotic susceptibility in the aortic arch in certain strains of mice.

Support or Funding Information

The work is supported by a National Institutes of Health (NIH) grant HL042630 to NM.
Development of compounds with mu‐opioid agonism and delta‐opioid antagonism as novel analgesics
Authors: Fernández Thomas Joaquín , Griggs Nicholas W , Traynor John R
Published: November 2023

Opioid analgesics exert both their beneficial and unwanted effects by activation of the mu‐opioid receptor (MOPR). Furthermore, repeated administration of opioid analgesics and subsequent chronic MOPR activation leads to opioid tolerance and physical dependence. Many attempts to eliminate the adverse effects of opioids by the synthesis of more potent and selective MOPR agonists have proved to be unsuccessful. It has been proposed that activation of MOPR with concurrent antagonism of the delta‐opioid receptor (DOPR) can reduce the development of opioid tolerance and reward. Here we report on the development of “mixed efficacy compounds” that activate MOPR and inhibit DOPR. We evaluated potential mixed efficacy compounds using two in vitro assays; 1) [35S]‐GTPγS binding assays to measure G protein activation in membrane preparations of cloned cell lines expressing either MOPR, DOPR, or kappa‐opioid receptors (KOPR). Full agonists at each opioid receptor (DAMGO, DPDPE, and U69,593, respectively) were used as standards for [35S]‐GTPγS binding. Maximum binding and potency (EC50) values of the novel compounds were determined from concentration‐effect curves. 2) Competition binding assays using [3H]‐diprenorphine (opioid antagonist) to determine affinity (Ki) values. Comparison of affinity and degree of agonism of the novel compounds at MOPR and DOPR revealed structure‐activity relationships to guide further chemical modification and drug development to improve compounds devoid of tolerance and dependence liabilities.

Support or Funding Information

Supported by DA‐03910
Inhibition of Opioid Induced Reward via Genetic and Pharmacological Manipulations
Authors: Davidson‐Knapp Rachel , Sandweiss Alesander J. , McIntosh Mary I. , Moutal Aubin , Hu Jackie , Giri Aswini , Yamamoto Takashi , Hruby Victor J. , Khanna Rajesh , Largent‐Milnes Tally M. , Vanderah Todd W.
Published: November 2023

Chronic pain affects approximately 100 million Americans for which opioids are the mainstay therapy. While physicians and patients alike are apprehensive about using opioids due to their side effects including respiratory depression and addiction, 259 million opioid prescriptions were written in 2012. Although opioids are the best available analgesics, they increase both positive and negative reinforcement, ultimately leading to addiction. The pro‐nociceptive or pain promoting, neurotransmitter Substance P (SP) and its corresponding receptor (NK1R) are found associated with dopamine neurons in the ventral tegmental area (VTA). Evidence exists suggesting that SP potentiates positive reinforcement of opiates leading to reward. Using in vivo microdialysis, we show that systemic morphine significantly increases SP release in the VTA, an effect mediated by inhibition of VTA GABAergic neurons. SP administered in the VTA significantly increases levels of dopamine in the nucleus accumbens (NAc), a reward processing center in the ventral striatum. Using CRISPR‐Cas9 knockdown of NK1R in the VTA, we show this prevents the activation of opiate reward, corroborating the results from a conditioned place preference paradigm (CPP). Finally, we developed a novel opioid agonist/NK1R antagonist, TY032, which was shown to inhibit acute and chronic pain in male rats. Importantly, our study found TY032 microinjection into the VTA did not result in an increase in extracellular dopamine release in the NAc. These data support targeting the dopamine reward circuitry and pain pathways with multifunctional opioid‐NK1R compounds could be a path to developing analgesics that lack the potential for abuse.

Support or Funding Information

Funding NIH/NIDA DA018717, NIH/NIDA DA013449.