bluuebunny/crossref_metadata_2025 huggingface dataset:
A plasma proteome is associated with carotenoid status in young Nepalese children
Authors: Eroglu Abdulkerim , Schulze Kerry Jean , Cole Robert N. , Christian Parul , Nonyane Bareng Aletta Sanny , Lee Sun Eun , Wu Lee Shu Fune , Khatry Subarna , West Keith P.
Published: November 2023

Background

Dietary carotenoids are naturally occurring pigments that may function in the body as vitamin A precursors, antioxidants, anti‐inflammatory agents or biomarkers of recent intake of vegetables and fruits, and thus be important for population assessments of nutritional status. Yet, carotenoid status is rarely assessed due to cost and difficulty. Quantitative plasma proteomics may offer an indirect approach to assess carotenoid status by identifying potentially predictive plasma proteins.

Objective

To detect and quantify a set of plasma proteins associated with major dietary carotenoids including β‐carotene, α‐carotene, β‐cryptoxanthin, lycopene, lutein and zeaxanthin in a cohort of 500 6–8 year old rural Nepalese children.

Design

Study children were born to mothers enrolled in an earlier antenatal micronutrient trial in Sarlahi, Nepal. Plasma carotenoid concentrations were measured by conventional HPLC analytical methods. For analysis of the plasma proteome, plasma aliquots were immunoaffinity‐depleted of six high abundance proteins, digested with trypsin, labeled with isobaric mass tags (iTRAQ 8‐plex reagents), and analyzed for protein relative abundance on tandem mass spectrometry (MS/MS). Linear mixed effects (LME) models were used to derive estimates of relative protein abundance, determine the direction and strength of correlation between individual proteins and plasma log2 concentration of each carotenoid, accepting a false discovery rate of q <0.10, and predicting, when feasible (AIC ≥ 30, q<0.10, p<0.0004), plasma carotenoid distributions.

Results

We quantified 982 plasma proteins in >10% of all child samples. Fifty‐one proteins were correlated with log2 β‐cryptoxanthin, primarily involved in lipid transport, oxidative stress, immune system regulation, and lipid peroxidation. Three modeled plasma proteins (APO‐A1, protein phosphatase, Mg2+/Mn2+ dependent, 1M and leucine rich repeat containing 47) explained 50% of the variance in log2 β‐cryptoxanthin (model R2=0.50). Plasma β‐carotene was associated with 4 proteins (orosomucoid 1, APO‐A1, pyruvate kinase, muscle [PKM] and TNFAIP3 interacting protein 1[TNIP1]). Two (APO‐A1 and PKM) were predictive of plasma β‐carotene (R2=0.66). Eleven plasma proteins were correlated with lutein/zeaxanthin, including APO‐A1, TNIP1 and 3 were modeled to be predictive of plasma concentration (model R2=0.55) (all q<0.10). No predictive models proteomes were identified for α‐carotene and lycopene.

Conclusions

We identified plasma proteomes that varied in size and were moderately predictive of plasma concentrations of β‐cryptoxanthin, β‐carotene and lutein/zeaxanthin. Plasma proteomics may offer an approach to assess carotenoid status in undernourished populations.

Support or Funding Information

Supported by the Bill & Melinda Gates Foundation (OPP5241).
Carotenoids and apo‐carotenoids in human plasma after continued consumption of high β‐carotene or high lycopene tomato juice
Authors: Cooperstone Jessica L , Riedl Ken M , Cichon Morgan J , Francis David M , Curley Robert W , Schwartz Steven J , Novotny Janet A , Harrison Earl H
Published: November 2023

Many studies have found associations between diets rich in carotenoids and a decreased risk for chronic diseases. Recent work has suggested that putative carotenoid metabolites resulting from the cleavage of β‐carotene (β‐C) and lycopene (LYC) by β‐C 15,15′‐oxygenase or β‐C 9,10‐oxygenase may be responsible for bioactivity attributed to the parent carotenoids. As a result, significant efforts have attempted to quantify these elusive carotenoid metabolites in vivo, with limited success. The objective of our study was to quantify both carotenoids and apo‐carotenoids in the blood of individuals consuming β‐C and LYC derived from whole foods. Healthy non‐smokers (n=35) consumed a low carotenoid diet for two weeks, and then consumed the same basal diet for 4 weeks with one of three juices: high β‐C tomato juice (360 mL, 30 mg β‐C, 35 μg apo‐carotenoids/day) or high LYC tomato juice (360 mL, 43 mg LYC, 120 μg apo‐lycopenoids/day) or a calorie matched cucumber juice control (360 mL, no detectable carotenoids). Targeted HPLC‐MS/MS methods were developed to quantitate apo‐carotenoids (apo‐8′, 10′, 12′, 14′, 15′‐carotenals, 13‐carotenone) and apo‐lycopenoids (apo‐6′, 8′, 10′, 12′, 14′, 15′‐lycopenals, 13‐lycopenone) in blood plasma with a limit of quantitation (LOQ) of ~50 pM. Plasma carotenoids were determined by HPLC. After four weeks, plasma β‐C levels reached 0.36, 0.62 and 3.18 μM in groups fed control diet, high‐LYC and high β‐C tomato juice, respectively, significantly increasing in the high‐β‐C group (P<0.001). Plasma lycopene reached 0.25, 1.40 and 0.58 μM in the control, high‐LYC and high β‐C groups, respectively, significantly increasing in the high‐LYC group (P<0.001). Plasma retinol was unchanged during this intervention, and not different among groups. Apo‐10‐ and 12‐carotenal were the only carotenals detected in plasma but not above our LOQ. Apo‐6′‐lycopenal was the only lycopenoid detected. Apo‐13‐carotenone was quantifiable in all subjects, measuring 0.46 ± 0.11 nM in control and 0.53 ± 0.12 in high‐LYC groups but higher (P<0.05) in those on the high β‐C juice at 1.01 ±0.27 nM at the end of study. These data suggest blood apo‐13‐carotenone increases with supplemental β‐C intake, but its occurrence is not dependent on it. New data also suggests that apo‐13‐carotenone can be derived from vitamin A.

Support or Funding Information

This study was supported by NCI‐USDA‐IAA #ACN15005‐001‐00000. Carotenoid and apocarotenoid analyses were conducted within the Nutrient and Phytochemical Analytical Shared Resource (NPASR) at the OSU Comprehensive Cancer Center (NIH P30 CA016058).
Obesity Leads to Tissue, but not Serum Vitamin A Deficiency
Authors: Trasino Steven E , Tang Xiao‐Han , Jessurn Jose , Gudas Lorraine J
Published: November 2023

Objective

There is increasing evidence that states of obesity negatively affect multiple nutrient sensing and metabolic pathways including vitamin metabolism, however little is known about the impact of obesity on vitamin A (VA)[retinol (ROL)], a nutrient that regulates expression of genes in numerous pathways essential for human development and health.

Methods and Findings

Using genetic (ob/ob; db/db), high fat diet‐induced obesity (DIO) murine models, and human liver samples, we demonstrate that DIO, and genetically obese mouse models have greatly reduced ROL levels in multiple organs, including liver, lungs, pancreas, brain, testes and kidneys, even though their diets have adequate VA. Despite the reductions in tissue levels of VA, serum levels of ROL were markedly elevated in obese mice. Organs from obese mice show impaired VA transcriptional signaling, including reductions in retinoic acid receptor (RARα, RARβ2 and RARγ) mRNAs and lower intracellular ROL binding protein Crbp1 (RBP1) levels in VA‐storing hepatic stellate cells. Reductions in organ VA signaling in obese mice correlate with increasing adiposity and fatty liver (steatosis), but with weight loss VA levels and signaling normalize. Consistent with our findings in obese mice, we show that increasing severity of fatty liver disease in humans correlates with reductions in hepatic VA, VA transcriptional signaling, and Crbp1 levels in VA storing stellate cells.

Conclusions

Our data demonstrate that overnutrition and obesity, typical of western lifestyles, can also lead to major reductions in tissue VA levels. We suggest that given the essential functions of VA in humans, “silent” tissue‐specific VAD has unappreciated effects on human health in obese individuals, affecting multiple organ systems.

Support or Funding Information

This research was supported by Weill Cornell funds and by NIH R01CA043796 and R01DE010389 to Lorraine J. Gudas, and Steven E. Trasino was supported by NCI T32 grant CA062948.
Carotenoid‐mediated protection of human retinal pigment epithelial cells against hypoxic stress
Authors: Draper Christian , Allison Geoffrey S , Gong Xiaoming , Rubin Lewis P
Published: November 2023

Purpose

Hypoxic stress and inflammation are central drivers of ischemic neovascular retinopathies, including retinopathy of prematurity and diabetic retinopathy. This purpose of this study is to investigate the properties of dietary carotenoids, especially retinal xanthophylls, in mitigating effects of hypoxia (e.g., by ischemia) on the developing retina.

Methods

Human RPE‐derived ARPE‐19 and immortalized hTERT‐RPE‐1 cells were exposed to graded concentrations of specific carotenoids (lutein, zeaxanthin, β‐carotene, lycopene, astaxanthin) for up to 24 h, and then subjected to hypoxic stress (1–2% O2). Carotenoid uptake in these cells was linear to 24 h reaching maximal uptake by ~2 days. Carotenoid effects on RPE cells were assayed for proliferation (cell counts, 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide [MTT] assays), viability (trypan blue exclusion), and apoptosis (various measures of early and late apoptosis).

Results

Lutein, β‐carotene, lycopene, and astaxanthin induced concentration‐dependent decreases in RPE cell proliferation at concentrations of ≥0.5 μM in both normoxic and hypoxic conditions. Equimolar concentrations of zeaxanthin were not associated with reduced cell viability under either condition. For these RPE cellular models, the hTERT RPE‐1 line displayed greater carotenoid‐mediated growth inhibition than did the ARPE‐19 line. Pretreating RPE cells with the individual carotenoids for 24 h prior to hypoxia significantly increased cell resistance to hypoxic cell death, lutein and lycopene being most potent.

Conclusions

This study demonstrates that carotenoid treatments protect the retinal pigment epithelial cells against hypoxic damage. These results apply for lutein, another biologically active xanthophyll (astaxanthin), β‐carotene, and lycopene. In these systems, lutein and zeaxanthin show different effects. These findings bear potential impact on prevention and treatment of ischemic retinopathies, help to define some molecular mechanisms, and prompt further research in this area.

Support or Funding Information

Seed grant from Texas Tech University Health Sciences Center El Paso
Tomato based supplement protects skin from UV damage and photo‐aging processes
Authors: HERMONI KARIN LINNEWIEL , Raz Golan
Published: November 2023

The Mediterranean diet, and particularly tomato rich diet is linked to favorable effects on human health and beauty. The benefits of healthy diverse nutrition on various aspects of skin wellness have been the subject of on‐going research. In recent years the role of tomato carotenoids in the photo‐protection of human skin and their contribution to beauty parameters has been gaining attention. As UV damage is a major risk factor for skin health and a major contributor to skin aging processes, protecting human skin from UV damage is of great value.

The aim of the current study was to investigate the effect of a supplement combining a carotenoid‐rich Tomato Nutrient Complex and Rosemary extract on cellular processes related to skin wellness and protection from UV damage

Pre‐clinical study in human keratinocytes revealed that both the Tomato Nutrient complex and the Carnosic acid present in Rosemary extract are potent activators of the antioxidant defense mechanism (EpRE/ARE). Furthermore, a synergistic inhibition of pro‐inflammatory cellular processes was evident. For example‐we found a synergistic inhibition of UV‐induced IL‐6 secretion following UV treatment. Of note, the effect of the whole fruit extract, containing several tomato phytonutrients was better than lycopene as a standalone as measured in several models. To further explore the mechanism by which the Tomato Nutrient Complex can help reduce photo‐damage we evaluated its protective effect in a human clinical trial. We found that tomato phytonutrients regulated the expression of a few UV‐inducible genes serving as biomarkers to skin health (eg ICAM‐I, HO‐1, MMP‐1). Moreover, preliminary results from a follow up study suggest that a supplement designed as a response to the pre‐clinical study and combining Tomato Nutrient Complex and Rosemary extract was protective in reducing erythema intensity following UV exposure.

In conclusion

This study suggests that tomato phytonutrients, especially when combined with Rosemary extract possess favorable, synergistic effects on various aspects of skin health, supporting the body's own defense mechanisms and allowing the skin to better cope with environmental challenges that are reflected in both skin health and skin appearance.

Support or Funding Information

This study was founded by Lycored Ltd
LIGHT AND ANTIBIOTIC STRESS FACTOR IN THE ACCUMULATION OF CAROTENOID PIGMENTS IN GREEN MICROALGAE ISOLATE
Authors: Oyebamiji Olufunke , Adeoso Abiodun
Published: November 2023

Carotenoid pigments are mainly C40 lipophilic isoprenoids and synthesized in most photosynthetic organisms (bacteria, algae, and plants), as well as in some non‐photosynthetic bacteria and fungi. While carotenoids are necessary to maintain normal health and behaviour of animals, animals do not synthesize carotenoids and therefore rely on their diet to obtain these compounds. Green microalgae isolates identified as Grasiella emersoni and Coelastrella sp. were isolated from soil samples and purified with Plant Preservative Mixture (PPM). Exposure to high light intensity (121.2 Klux) while culturing made these green isolates turn orange. A laser confocal microscope was used to compare emitted fluorescence in the chloroplast of green and orange cells, and an overlay was acquired. The green and red cells were also excited with Argon 488 spectrum, and the emitted wavelength from 500 – 750 nm was collected and plotted. The Scanning Electron Microscope (SEM) images were acquired to show the effect of the stress factors on the cells. The chloroplast in the red cells emitted fluorescence mostly in the carotenoid emission range and weakly in the chlorophyll range, therefore the chlorophyll fluorescence emission is masked by carotenoid fluorescence in the overlay picture. The 488 spectrum emission wavelength of the red microalga showed an additional peak in the carotenoid emission region (550 nm) in addition to the chlorophyll peak in the 680 nm region. This shows the accumulation of carotenoids in the red cells of the microalgal isolate.
Efficacy of lycopene to prevent against atrazine‐induced cardiotoxicity via modulation of nitric oxide and inflammatory NF‐κB pathways
Authors: Li Xue‐Nan , Lin Jia , Qin Lei , Xia Jun , Zhu Shi‐Yong , Li Jin‐Long
Published: November 2023

Atrazine (ATR), a synthetic herbicide in the 2‐chloro‐s‐triazine family, has been widely used in crop lands and often detected in some crops, in soil, environmental water and drinking water samples in recent years, which is considered as a potential threat to cardiovascular health. Persistent prevalence of heart disease and its high morbidity and mortality suggest that there are significant gaps in our understanding of the mechanisms that impair cardiovascular health and that better preventive strategies are needed to manage heart disease. Lycopene (LYC), a polyunsaturated hydrocarbon phytochemical present in red fruit and vegetables, plays roles in preventing heart disease. However, true confirmation that cardioprotective effects of LYC against ATR‐induced heart injury occured through modulation of the inflammation response is lacking. To ascertain the chemoprevention of LYC on ATR‐induced cardiotoxicity, male Kunming mice were treated with LYC (5mg/kg) and/or ATR (50mg/kg or 200mg/kg) by gavage administration for 21 days. The serum tumor necrosis factor‐α (TNF‐α) concentration were quantified by 125I Radioimmunoassay (RIA) Kits. The nitric oxide (NO) content and nitric oxide synthase (NOS) activities were determined by assay kits. The mRNA expressions of TNF‐α, IL‐6, COX‐2, IL‐1β and TGF‐β were tested by quantitative real‐time polymerase chain reaction (real‐time RT‐PCR). Furthermore, Western blotting was used to determine whether the signaling pathway NF‐κB was involved in the inflammatory action. These results indicated that LYC significantly protected the heart against ATR‐induced histological alterations, including increased NO content and NOS activities, up‐regulation of pro‐inflammatory (TNF‐α, IL‐6, COX‐2 and IL‐1β), and down‐regulation of anti‐inflammatory (TGF‐β) cytokines and activation of the TRAF6‐NF‐κB pathway. ATR induced cardiac damage via enhancing NO production and triggering the inflammatory response. Supplementary LYC significantly alleviated the cardiac injury via modulating NO and NO‐generating systems and blocking the TRAF6‐NF‐κB pathway. This work helps not only in understanding the mechanism of the ATR‐induced environmental cardiology but also in developing LYC chemoprevention for minimizing the harmful influences of ATR in the environment.

Support or Funding Information

China New Century Excellent Talents in University (No. NECT‐1207‐02), National Natural Science Foundation of China (No. 31572586) and Academic Backbone Project of Northeast Agricultural University (No. 15XG16).
Effects of Potatoes and Other Carbohydrates Consumed at Breakfast on Cognition, Glycemia and Satiety in Children
Authors: Lee Jennifer J. , Wong Vincent C.H. , Cleary Shane , de Zepetnek Julia Totosy , Fiocco Alexandra J. , Bellissimo Nick
Published: November 2023

Background

There is a positive association between regular breakfast consumption and cognitive performance in children, however, little is known about the role of macronutrient composition on cognition. The objective of the study was to examine the effects of 50 grams of available carbohydrates from potatoes and other carbohydrates on cognitive performance, glycemia and subjective appetite in 9–14 year old children.

Methods

Using a within‐subject cross‐over design, 22 children (age=12.4±0.3) were exposed to six counterbalanced conditions, each separated by one week, in which they consumed 50 grams of available carbohydrates from mashed potatoes (426kcal), French fries (424kcal), hash browns (515kcal), rice (407kcal), beans (476kcal), or continued to fast (no breakfast condition) within 2 hours of awakening following a 12‐hour overnight fast. In each condition, children underwent a battery of cognitive tests assessing short‐term and long‐term verbal declarative memory, spatial memory, short‐term auditory memory, working memory, and information‐processing speed over a 3‐hour period. Children provided capillary blood glucose and subjective appetite ratings at baseline (0min) and at 10, 30, 60, 120, and 180 min post‐meal consumption.

Results

Analyses showed that blood glucose incremental area under the curve (mean mmol·min/L ± SEM) was highest after rice (160±16.8) compared with beans (84.0±12.7) and hash browns (106.8±13.8) (p<0.01). Although alertness was higher after French fries (p<0.01), hash browns (p<0.01), mashed potatoes (p<0.01), and rice (p=0.04) compared with beans and meal skipping, children recalled more words after consuming French fries only, compared with mashed potatoes (p<0.01) and rice (p=0.03). Subjective average appetite (mm/kcal) was lowest after mashed potatoes compared with all other test treatments (p<0.01).

Conclusions

This study suggests that different forms of carbohydrate intake differentially impact cognitive function and appetite, independent of glycemia. Future studies investigating the physiological and neurochemical mechanisms for cognitive performance and food intake control in breakfast‐eating and non‐breakfast eating children are recommended.

Support or Funding Information

This study was supported by the Alliance for Potato Research and Education (APRE).
Evaluation of the Association of Toll‐Like Receptor 4 and BMI with Postpartum Depressive Symptomatology
Authors: Molkenthin Brittany A , Judge Michelle P , Young Erin E , Beck Cheryl T
Published: November 2023

Obesity has been associated with elevated Toll‐like receptor 4 (TLR4) expression. An imbalance in TLR4 expression and increased inflammatory load may play a role in the regulation of mood and in the etiology of mood disturbances. This study was designed to explore the underlying correlations between maternal BMI, circulating TLR4, and postpartum depressive symptoms. This exploratory secondary analysis utilized existing samples (n=42) during pregnancy and postpartum periods. Maternal plasma samples were collected at 20, 36–38 weeks gestation, and 2 weeks postpartum. Existing plasma samples were used to quantify TLR4 using ELISA. The Postpartum Depression Screening Scale (PDSS) was used to evaluate depressive symptoms at four time points (2 weeks, 6 weeks, 3 months, and 6 months) during the postpartum period. Pregnancy BMI was positively correlated with average PDSS score (r = 0.352, p <0.05) across the four time points. TLR4 at 2 weeks postpartum was positively correlated with the PDSS score at 6 months postpartum, (r=0.396, p<0.05). TLR4 and PDSS scores were not significantly correlated at the 2 week, 6 week, or 3 month postpartum time points. Our findings suggest that higher pregnancy BMI and greater inflammatory activation may increase risk for postpartum depressive symptoms at 6 months postpartum. These preliminary findings indicate a need for further large‐scale study of the interrelationships between BMI, inflammation, and postpartum depressive symptoms in an effort to inform future development of precision medicine initiatives to predict, prevent, and treat postpartum depression.

Support or Funding Information

Donaghue Foundation, University of Connecticut Summer Undergraduate Fund
Modulation of Protein Status in Humans Leads to Preference for Increased Portions
Authors: Davidenko Olga , Fromentin Sébastien , Barbillon Pierre , Fromentin Gilles , Tomé Daniel , Darcel Nicolas
Published: November 2023

Introduction

Protein together with energy is an essential component of the diet. Implicit control of protein consumption is a key element of food decision‐making and behavior in humans. However, it is unclear which food characteristics, especially sensory, are the determinants of food choices guiding to adequate protein intake. A low‐protein diet is known to induce unconscious search for foods containing protein. By comparing food preferences of human subjects under a low‐protein diet to preferences of the same subjects subjected to a balanced diet, this study aimed at identifying implicit determinants of protein level in common foods.

Materials and Methods

23 healthy volunteers (13 women) 18 to 35 years old, non‐overweight (BMI between 18 and 25 kg/m2) followed two successive dietary interventions in a randomized crossover design during which they consumed either a diet containing 0.5g of protein/kg body weight/day, or 1.4g protein/kg/day. Both diets were iso‐energetic and variations in protein content were compensated by variations in both carbohydrates and fats. Experimental diets lasted 4 days each and were separated by a 10‐day wash‐out period during which participants were instructed to go back to their normal diet. At the beginning and at the end of each experimental diet period participants completed an on‐screen task during which they choose the preferred food from two food photographs. Foods present on photographs differed in protein content, portion size, or sensory qualities. A total of 153 pairs was used. Based on this task, preference scores for each food was estimated using the Bradley‐Terry method for analysis of paired comparisons. Effect of subjects' protein status on preference scores and its interaction with food sensory and nutritional characteristics was then evaluated.

Results

Preference analysis showed a significant effect of subjects' protein status on food preference scores (p=0.0047). A significant interaction was found between protein status and portion size (p=0.0002), a low‐protein diet resulting in a preference for larger portions. Other food characteristics such as protein content of foods and their sweet or salty taste, did not appear to affect preferences in a situation of low protein status (p=0.11 and p=0.14, respectively).

Conclusion

This study showed an alteration of food preferences induced by a low‐protein diet, observed after 4‐day dietary intervention. Subjects following a low‐protein diet appear to prefer larger food portions that could be interpreted as an attempt to restore protein balance.

Support or Funding Information

The study was funded by a grant from French Nutrition Society
Early life diet alters sleep architecture following an acute stress: The potential role of milk oligosaccharides
Authors: Chichlowski Maciej , Morairty Stephen , Berg Brian M.
Published: November 2023

Stress exposure can produce disruptions in the sleep cycle that may contribute to altered cognitive performance. Prebiotics can selectively enhance select gut microbial species that may promote favorable response to stressrobustness. Our previous studies showed that a milk oligosaccharide, sialyllactose, supported normal microbial communities (similar to non‐stressed animals) and behavioral responses during stressor exposure, potentially through effects on the gut microbiota–brain axis. The aim of the current study was to determine whether early life dietary oligosaccharides would modulate the sleep cycle and protect sleep architecture following stress. We hypothesized that diet containing a blend of prebiotics (galactooligosaccharides, GOS+polydextrose, PDX) and/or sialyllactose (Lacprodan SAL‐10®; SL) would mitigate stress induced alterations of electrophysiological markers of sleep. Male Sprague Dawley rats (postnatal day (P)21) were placed on one of the experimental diets for 30d: a) SL [2.2g/kg], b)GOS+PDX [7g/kg each], c) GOS+PDX [7g/kg each] + SL [2.2g/kg] or d) Control[cellulose as fiber source]. Telemetry devices were implanted on P64 to examine the differences in electroencephalograph (EEG) and electromyograph (EMG)measurements. Baseline 24h EEG recordings were performed on P84. Rats were exposed to an acute stressor (inescapable stress) on P85 in order to examine the potential protective effects of our experimental diets on stress‐induced sleep/wake cycle. An additional group of Control animals remained undisturbed(Control Unstressed). There were no differences in food intake and body weight gain among the groups. There was a normal EEG distribution of power across the 24 h period under baseline conditions for all diets. During baseline, GOS+PDX+SL group had decreased waketheta frequency compared to Control Unstressed group (P<0.05). All stressed groups slept more (both NREM and REM) compared to the Control Unstressed group. Test diet groups had less overall waking following stress compared to the control animals. Rats on GOS+PDX diet had more overall NREM (NREM consolidation)compared to Control Unstressed animals (P<0.05). REM alpha and beta power were increased in rats on GOS+PDX and SL diets compared to control animals during baseline (prior to stress exposure) and following stress (P<0.05). Overall, these data demonstrate that an early life diet containing GOS+PDX and/or SL can increase NREM sleep consolidation and mitigate stress‐induced sleep disruptions in adulthood. Ongoing microbiome analysis might provide further insights on the mechanism of actions of this novel dietary intervention.

Support or Funding Information

Supported by Mead Johnson Nutrition.
A possible emerging role of Stachys siedlbodii MIQ extract in neuroprotection: in vitro and in vivo
Authors: Ravichandran Vijaya Abinaya , Kim Mina , Cha Youn Soo
Published: November 2023

Dementia is the most common problem affecting older people; recently demonstrated the importance of oxidative process and loss of cholinergic neuron in parts of the brain subserving aspects of memory. Plants are an important source of essential nutrients, such as choline, vitamins, phenyl ethanoid glycosides and saponins, etc. These nutrients have shown promising effect to prevent or delay the onset of neurological disorder. This work aims to evaluate the potential effect of Stachys siedlbodii MIQ (SS) against oxidative stress induced by hydrogen peroxide (H2O2) in SK‐N‐SH cells, and memory enhancement in ICR mice using the passive avoidance test. This study also investigated the role of cholinergic activity in SS induced brain tissue. In SK‐N‐SH cell culture, SS could partially antagonize the effects of 150 μM H2O2 on cell viability. In vivo study, SS (100 mg/kg, 250 mg/kg, and 500 mg/kg) was administered orally to mice for 4 weeks. Treatment with SS, based on dose dependent manner had a significantly longer step‐through latency time than the control suggesting retained of fear memory. SS improved cholinergic system reactivity by increased level of acetylcholine in hippocampus and frontal cortex. These results suggest that SS administration significantly ameliorate the memory retention, by improving cholinergic activity on mice brain.

Support or Funding Information

This research was financially supported by the Ministry of Trade, Industry, and Energy (MOTIE), Korea, under the “Regional Specialized Industry Development Program” supervised by the Korea Institute for Advancement of Technology (KIAT)
A randomized double‐blind, placebo controlled, four‐arm parallel study investigating the effect of a broad spectrum wellness beverage on mood state in healthy, moderately stressed adults
Authors: Aruoma Okezie , Evans Malkanthi , Anthony Joseph , Guthrie Najla , Landes Bernie
Published: November 2023

Objective

To investigate the effect of a broad spectrum wellness beverage (Zeal Wellness) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults.

Methods

A randomized, double‐blind, placebo‐controlled, clinical trial was conducted on 100 eligible participants for 4 weeks. Participants were randomized to one of four groups including; Zeal Wellness (ZW) once daily (1‐dose‐ZW), ZW twice daily (2‐dose‐ZW), Placebo once daily (1‐dose‐Placebo) and Placebo twice daily (2‐dose‐Placebo). At all visits a Stress/Vitality questionnaire was administered and anthropometric measures were collected. The Profile of Moods (POMS) Questionnaire was administered at Day 0, 8, 15 and 29.

Results

Participants supplemented with 2‐dose‐ZW reported a 6.6% decrease in POMS‐TMD (p<0.05) and a 6.8% decrease in the Anger‐Hostility mood state (p<0.022) compared to the combined placebo group at day 29. The 2‐dose‐ZW was shown to provide a 12.8% greater improvement in POMS‐TMD when compared to 1‐dose‐ZW in participants after 29 days of supplementation (p = 0.014). Within groups, there was a 22.4% decrease in POMS‐TMD in participants supplemented with 2‐dose‐ZW and a 9.6% decrease in POMS‐TMD in participants supplemented with 1‐dose‐ZW. Additionally, participants receiving 2‐dose‐ZW showed marked improvements in the POMS T‐score Iceberg profile that represented a shift to a more‐healthy profile. Safety markers including hematology, clinical chemistry, vitals, and anthropometric measures showed no difference between groups after 29 days of supplementation.

Conclusion

Participants supplemented with 2‐dose‐ZW significantly decreased POMS‐TMD, Anger‐Hostility mood state and elicited a shift in the POMS T‐score iceberg to a more‐healthy profile compared to combined placebo.

Support or Funding Information

Zurvita, Houston, Texas, 77024
Why Kids Should Play with Their Phone During Dinner: Active Engagement Can Decrease Food Consumption
Authors: Tal Aner , Wansink Brian
Published: November 2023

Prior research has consistently demonstrated increased in food consumption under distraction (e.g., DeCastro and Brewer 1992; Hetherington et al. 2006; Wansink et al. 2004; Tal and Wansink 2014). In the current research, we aim to explore whether active engagement with content (vs. passive consumption) leads to opposite effects.

For‐credit participants (N = 86) snacked on 62 gram bowls of M&Ms while undergoing distraction. Half were instructed to go online with their smartphones and visit websites they like, and the other half were left with no special instructions (control). We measured leftover M&Ms. Participants who used their smartphones at 37% less (12 grams) than those in the control group (19 grams). The effect was significant at a .02 level, t(84) = 2.35.

The study provides initial evidence that distractions that offer active (vs. passive) engagement may have different effects than passive distractions. Past research has consistently demonstrated increases in food consumption due to distraction (Wansink et al. 2004). However, in the current study we found that actively engaging with content as happens during online browsing may lead to effects that are the reverse of regular, passive distraction. Future research should replicate these effects and explore what types of distractions in particular may lead to reversal of the regular effects of distraction.
Relationship between polyphenol consumption and physical activity and sleep
Authors: Grobe Stephanie , teRiele JoAnne , Martin Rebecca , Boolani Ali
Published: November 2023

Objective

The purpose of this study was to investigate the relationship between polyphenol consumption, physical activity, and hours of sleep.

Methodology

Participants (n=912; Males=555, Females=357; age=21.18±4.85 years, BMI=25.10±5.06) were administered an online survey that included questions about: polyphenol (caffeine, fruit, vegetable, energy beverages, and chocolate) consumption frequency; physical activity frequency and duration; and number of hours slept on a typical night. A bi‐variate Pearson correlation was used to determine relationships between polyphenol consumption, number of minutes of moderate (MPA) and high (HPA) intensity physical activity/week, and number of hours of sleep.

Results

Analysis yielded statistically significant relationships between: energy drink consumption and sleep (p<.01, R=−0.15); fruit consumption and HPA (p<.01, R=0.095); vegetable consumption and HPA (p<.01, R=0.104) and MPA (p<.01, R=0.100); chocolate consumption and HPA (p<.01 and R=.105); and total polyphenol consumption and HPA (p<.01, R=0.134) and MPA (p<.01, R=0.095).

Conclusion

A positive relationship was noted between healthy eating habits and moderate to high intensity activity levels. People who eat healthier may also adopt healthier lifestyle habits such as exercise. However, results also indicate that increased energy beverage consumption will negatively correlate with the number of hours of sleep. These relationships should be farther explored because the survey administration was limited to a small town in upstate New York.

Support or Funding Information

No funding
Acute Effects of Wild Blueberry Intake on Metabolic Markers and Cognitive Performance in Middle‐Aged Adults
Authors: Rahman Sajida , Whyte Adrian , Huang Yancui , Williams Claire , Krikorian Robert , Burton‐Freeman Britt
Published: November 2023

BACKGROUND

Consumption of polyphenols has been associated with improvements in cognitive function in children (aged 8–10 years old), young adults (18–21 years old) and older adults (65–80 years old). In this study, we investigated the effect of wild blueberry (WBB) consumption on cognitive performance in middle aged adults (45–60 years old) and examined the relationship of cognitive outcomes with metabolic control.

METHODS

In this randomized, single‐blind, 2‐arm, cross‐over trial, 29 middle aged men and women were asked to consume a high carbohydrate, moderate fat meal with 1 cup fresh weight equivalent freeze dried WBB drink or control beverage (flavored lemonade). Cognitive tests measuring response interference, executive/working memory, and performance in learning, memory recall and recognition were performed immediately before and every 2 hours after meal consumption for 8 h. Blood samples were collected at defined time points over 8 h after meal intake.

RESULTS

Preliminary analysis showed significant effects for treatment (p=0.01) and time (p=0.02) with respect to response inhibition on a task assessing executive function. Response inhibition was significantly higher after WBB consumption compared to control (p<0.05) at the 2 hour time point and a trend for higher response inhibition was observed at the 4 hour time point (p = 0.08). Changes in postprandial insulin were significantly different by treatment (mean ± SE; WBB, 35.0 ± 3.0 uIU/mL, Control, 40.0 ± 3.0 uIU/mL, p=0.02) and time (p<0.0001), whereas glucose and TG were different by time only (p<0.0001 for both). Incremental area under the curve analysis also showed significantly reduced insulin exposure (control, 236.3 ± 32.7 uIU/mL*h vs WBB, 204.8 ± 33.4 uIU/mL*h, p=0.0431) with no significant change in glucose or TG (p>0.05) between WBB and control.

CONCLUSION

These results support a role of WBB in acute facilitation of cognitive performance on the more demanding conditions of a response inhibition task and enhancing insulin action when consumed with a meal in middle aged adults. These findings, in conjunction with similar reports in young and older aged groups, support the notion that wild blueberry supplementation can be beneficial with respect to neurocognitive and metabolic function throughout the life span.

Support or Funding Information

Wild Blueberry Association of North America
α‐Tocotrienol protects primary hippocampal neurons against oxidative stress‐mediated ΔN‐Bcl‐xL formation in the mitochondria
Authors: Park Han‐A , Jonas Elizabeth A
Published: November 2023

The mitochondrial pro‐survival protein, B‐cell lymphoma‐extra large(Bcl‐xL) enhances energy metabolism and mitochondrial/neuronal function, but it is also capable of forming an N‐terminus cleaved‐, pro‐death fragment, ΔN‐Bcl‐xL, under excitotoxic stimulation. Neuroprotective properties of α‐tocotrienol (TCT) have been previously reported in both in vivo and in vitro systems. However, the mechanism of neuroprotection, particularly in mitochondrial targets, is not fully understood. In this study, we tested whether excitotoxic (glutamate)‐induced ΔN‐Bcl‐xL formation is mediated by redox homeostasis in neurons, and whether the neuroprotective properties of α‐TCT occur via regulation of ΔN‐Bcl‐xL formation in the mitochondria. Primary hippocampal neurons were treated with α‐TCT, glutamate, or a combination of both, and then assayed for caspase 3 and ΔN‐Bcl‐xL formation, mitochondrial function, redox status, and neuronal viability. Glutamate caused abnormalities in mitochondrial function leading to neuronal death. The antioxidant α‐TCT protected neurons from glutamate‐induced mitochondrial dysfunction and cytotoxicity. α‐TCT treatment protected against cleavage of full length anti‐apoptotic Bcl‐xL to form pro‐death ΔN‐Bcl‐xL. α‐TCT significantly attenuated glutamate‐induced reactive oxygen species (ROS) formation in primary hippocampal neurons, reduced caspase 3 activation at the mitochondria and reduced‐ΔN‐Bcl‐xL formation at the mitochondria. Our data suggest that mitochondrial ROS production is responsible for glutamate‐induced ΔN‐Bcl‐xL expression. We find that ΔN‐Bcl‐xL is formed at mitochondria, suggesting that caspase 3 is activated there to cleave a specific mitochondrial protein, full length Bcl‐xL. Clearance of mitochondrial ROS may be an important protective mechanism against ΔN‐Bcl‐xL‐mediated mitochondrial dysfunction and neuronal death.

Support or Funding Information

NIH NS045876
The Loss of Copper and the Increase in COMMD‐1 in Ischemic Hearts of Mice
Authors: Li Kui , Li Chen , Hu Sheng , Fu Chunyan , Kang Y. James
Published: November 2023

Myocardial ischemia is accompanied by the loss of copper. The present study was undertaken to understand the relationship between copper loss and alterations in copper efflux transporters. Male mice (C57 BL/6J) were subjected to left anterior descending artery (LAD) ligation to induce myocardial ischemia. The heart was harvested at different time points after the operation. Copper concentration in the heart was measured by atomic absorption spectrometry (AAS). Copper metabolism MURR1 domain (COMMD‐1) mRNA and protein levels were determined by RT‐PCR and western blot. Copper concentrations in the infarct area were decreased at the 4th day after ischemia, and further decreased thereafter. Prior to the gradually decreasing in copper concentrations, COMMD‐1 protein level was significantly increased at the 1st day in the infarct area. The result suggests that during the process of myocardial infarction, COMMD‐1 might play a key role in the loss of copper.

Support or Funding Information

This study is supported by National Science Foundation of China (81230004).
Loss of ZIP12 Leads to Mitochondrial Dysfunction and Reduced Neurite Outgrowth in Neuro‐2A Neuroblastoma Cells
Authors: Tang Tony Z. , Hart Matthew D. , Nacke Mariah R. , Wu Lei , Fiddler Joanna L. , Clarke Stephen L. , Smith Brenda J. , Lin Dingbo , Chowanadisai Winyoo
Published: November 2023

Introduction

Zinc is an essential micronutrient needed for proper neuronal development and brain function. Previous studies on the zinc transporter gene, ZIP12, have shown that it is necessary for neuronal development. However, it is not known what cellular processes require ZIP12 for neuronal function.

Methods

Loss of ZIP12 function in Neuro‐2A cells was achieved by ZIP12‐targeted shRNA depletion via plasmid transfection or the generation of a ZIP12 knockout (KO) cell line by Cas9/CRISPR‐mediated genome editing. ZIP12‐depleted cells were differentiated in medium containing retinoic acid (2% fetal bovine serum in DMEM + 20 uM retinoic acid) for 48 hours and assayed for cellular oxygen respiration, a measure of mitochondrial function, using the Seahorse XFe96 flux analyzer or neurite length by microscopy using ImageJ software and the NeuronJ plugin. Different measures of mitochondrial function include maximal respiration, proton leak and ATP production capacity were assessed by the Seahorse flux analyzer. Sensitivity of ZIP12‐depleted cells to a sublethal dose of rotenone, a mitochondrial inhibitor, was measured by incubating ZIP12‐depleted cells in 2.5 nM rotenone for 48 hours in differentiating media, followed by neurite imaging. The effect of ZIP12 KO on mitochondrial abundance during differentiation was quantified by Mitotracker Green fluorescence staining relative to Hoescht 33342 nuclear dye intensity, as measured using the BioTek Synergy HT plate reader. The effect of ZIP12 KO on neurite length during differentiation was also determined.

Results

ZIP12‐targeted shRNA depletion resulted in reduced ATP production, proton leak and maximal respiration of mitochondria compared to control shRNA transfected cells, as measured by the Seahorse flux analyzer. Rotenone exposure during differentiation resulted in significantly shorter neurites in ZIP12 shRNA transfected cells. Similarly, the ZIP12 KO cells displayed blunted neurite extension during differentiation compared to uncut control cells with functional ZIP12. Furthermore, mitochondrial abundance of ZIP12 KO cells during differentiation was also significantly decreased.

Conclusions

Loss of function of ZIP12 impairs neuronal development and mitochondrial function in Neuro‐2A cells during differentiation. ZIP12 may play an important role in the regulation of mitochondria which subsequently affects proper neuronal development.

Support or Funding Information

This work was supported by Faculty Startup funds from the Oklahoma State University Office of Research and a grant from the Oklahoma Center for the Advancement of Science and Technology (HR16‐060).
Modifiers of the Effect of Maternal Multiple Micronutrient Supplementation: an individual patient data meta‐analysis of 17 randomized trials
Authors: Smith Emily R. , Shankar Anuraj , Wu Lee , Aboud Said , Adu‐Afarwuah Seth , Ali Hasmot , Apriatni Mandri , Arifeen Shams , Ashorn Per , Bhutta Zulfiqar A , Christian Parul , Devakumar Delanjathan , Dewey Kathryn G , Friis Henrik , Gomo Exnevia , Gupta Piyush , Kæstel Pernille , Kolsteren Patrick , Lanou Hermann , Maleta Kenneth , Mamadoultaibou Aissa , Msamanga Gernard , Osrin David , Persson Lars Åke , Ramakrishnan Usha , Rivera Juan A , Rizvi Arjumand , Sachdev HPS , Urassa Willy , West Keith P , Zagre Noel , Zeng Lingxia , Fawzi Wafaie , Sudfeld Christopher
Published: November 2023

Objective

To identify individual‐level effect modifiers of the effect of multiple micronutrient supplementation (MMS) containing iron and folic acid (IFA) during pregnancy, compared to IFA alone, on the risk of stillbirth, infant mortality, and birth outcomes.

Methods

We performed an individual patient data meta‐analysis. Study‐specific estimates were generated, and we pooled subgroup estimates using fixed effects models.

Findings

We included 17 randomized controlled trials (including 112,953 pregnancies). MMS resulted in greater reductions in low birthweight (RR 0.81; 95% CI: 0.74–0.89), small‐for‐gestational age births (RR 0.91; 95% CI: 0.87–0.96), and six‐month mortality (RR: 0.71; 95% CI: 0.60–0.86) among anemic (hemoglobin <110g/L) as compared with non‐anemic pregnant women. MMS had a greater impact on preterm birth among underweight pregnant women (body mass index <18.5kg/m2) (RR: 0.84; 95% CI: 0.78–0.90) compared to those with BMI ≥18.5 (RR: 0.94; 95% CI 0.90–0.98) (p value heterogeneity 0.01). MMS provided significantly greater reductions in infant mortality for female (RR: 0.87; 95% CI: 0.77–0.99) as compared to male infants (RR: 1.05; 95% CI: 0.93–1.18) (p value heterogeneity 0.04). In general, the survival and birth outcome effects of MMS were greater with high adherence (≥95%) to supplementation.

Conclusion

MMS produced greater birth outcome benefits for pregnant women with indicators of nutritional deficiency and improved survival for female infants.

Support or Funding Information

None.
Micro‐nutrient Supplementation Affects Mood Depending on Dopamine and Serotonin Single Nucleotide Polymorphisms Associated with Psychiatric Symptoms
Authors: Benton David , Long Sara‐Jayne , Young Hayley Anne
Published: November 2023

As a meta‐analysis found that micro‐nutrient supplementation improved mood (Long & Benton, 2013), to establish mechanisms and to pin‐point those more likely to benefit, the roles of various polymorphisms were examined. For three months in a double‐blind trial, 200 young healthy male adults took vitamin/mineral supplements or a placebo and ratings of mood were obtained. With rs1800497 (Taq1A; dopamine D2 receptors) those with the CT, but not other alleles, benefitted from supplementation. Similarly with rs1800955 (dopamine D4 receptor) those with the CC allele benefitted. Rs2550946 is associated with the dopamine transporter molecule (DAT1 – SLC6A3) and the reports of feeling depressed declined in those with the TT allele. When serotonin was considered there was an influence of rs1050565 (Human Serotonin Transporter gene); in those with the AA allele the consumption of vitamins/minerals rather than a placebo resulted in a significant improvement in mood, something not true in those with other genetic make ups. Thus gene/nutrition interactions were found where genes associated with psychiatric symptoms responded to micro‐nutrient supplementation.

Support or Funding Information

The research received no external funding