bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of Antioxidant Enzymes by Soybean‐Derived Glyceollins is Independent of p53 Expression in Human Colorectal Cancer Model
Authors: Gwon Yunjeong , Jo Gwang‐Rae , Woo Yaejin , Jeong Gain , Kim Jungeun , Averilla Janice Nullan , Seo Hyelin , Ju Sunghee , Jang Jin Ho , Oh Jisun , Kim Jong‐sang 
Published: November 2023

Soybean‐Derived glyceollins were found to induce antioxidant/phase 2 detoxifying enzymes through Nrf2‐mediated signaling pathway, and thus protect cells from exogenous oxidative insult. As Nrf2 signaling pathway has been reported to be suppressed by p53, we hypothesized that Nrf2 activation by glyceollins could also be influenced by p53. Both p53‐wildtype and p53‐knockout HCT116 cells were treated with glyceollins, and then were examined for cell growth and Nrf2‐dependent cytoprotective reactions. Glyceollins treatment increased the expression levels of Nrf2 and its downstream enzymes in both p53‐wildtype and knockout cells in a similar fashion although the expression of p53 and p21 was significantly increased in p53‐wildtype HCT116 cells but not in p53‐knockout cells by glyceollins. In contrast, the treatment of p53‐knockout human colon carcinoma HCT116 cells with either sulforaphane or tBHQ caused dramatic increase in the reporter luciferase gene expression in the cells transfected with antioxidant response element (ARE) and luciferase gene construct, while the compounds led to marginal increase in the reporter gene expression in p53‐wildtype HCT116 cells. Moreover, sulforaphane induced cell growth in wild type HCT116 cells that was inhibited by treatment of SnPP, a HO‐1 inhibitor, while glyceollins did not affect the growth of both types of cells. Thus, the crosstalk between Nrf2 signaling pathway and p53 axis were found to be dependent on Nrf2 activators. In conclusion, these observations implicate the necessity of customized anticancer strategies depending on p53 status as well as the types of Nrf2 inducers.Support or Funding InformationThis study was funded by National Research Foundation (Grant No. R2014R1A2A2A01005773), Ministry of Science, ICT and Future Planning, Republic of Korea
Oxylipids derived from arachidonic and dihomo‐gamma‐linolenic acids are associated with colon polyps in adult males
Authors: Yin Zhe , Pickens C. Austin , Sordillo Lorraine M , Fenton Jenifer I. 
Published: November 2023

Oxylipids are potent lipid mediators associated with inflammation‐induced colon carcinomas and colon tumor survival. Therefore, oxylipid profiles may be useful as biomarkers of colon polyp presence. The aim of the study was to investigate the relationship between plasma non‐esterified oxylipids and the presence of colon polyps. A total of 123 men aging from 48 to 65 were categorized into 3 groups: those with no polyps, those with 1 or more hyperplastic polyps, and those with 1 or more adenomas. Plasma non‐esterified oxylipids were analyzed using solid phase extraction and quantified using a targeted HPLC tandem mass spectrometric analysis. Statistical analyses included Kruskal‐Wallis one‐way ANOVA with Dunn's test for multiple comparison and generalized linear models. In general, monohydroxy oxylipids derived from the omega‐6 family were significantly increased in those with polyps. Concentrations of 5‐hydroxyicosatetraenoic acid (HETE), 11‐HETE, 12‐HETE, 15‐HETE and 15‐hydroxyeicosatrienoic acid (HETrE) were significantly higher in those with hyperplastic polyps (4.86 nmol, 0.93 nmol, 12.11 nmol, 1.02 nmol, and 0.33 nmol respectively) and adenomas (4.61 nmol, 0.81 nmol, 10.05 nmol, 0.93 nmol, and 0.44 nmol respectively) compared to those with no polyps (1.86 nmol, 0.39 nmol, 7.83 nmol, 0.63 nmol, and 0.24 nmol respectively). On the other hand, the concentration of endocannabinoid arachidonyl ethanolamide (AEA), derived from the non‐oxidative metabolism of arachidonic acid, decreased significantly in those with adenomas (0.18 nmol) compared to those with hyperplastic polyps (0.25 nmol). Even after adjusting for age and smoking in regression models, these oxylipids remained significantly associated with polyps. Since many of these oxylipids are formed through oxygenation by lipoxygenases (i.e., 5‐, 12‐, and 15‐HETE, and 15‐HETrE) or auto‐oxidative reactions (i.e., 11‐HETE), this may indicate that lipoxygenase activity and lipid peroxidation are increased in those with colon polyps. In addition, since oxylipids such as 5‐, 12‐, and 15‐HETE and AEA are signaling molecules involved in inflammation regulation, these oxylipids may have important functions inflammation‐associated polyp formation. Future studies should investigate if these oxylipids may be useful as potential biomarkers of colon polyps, and verify our findings in larger and more diverse populations.Support or Funding InformationFunding sources NIH R03CA142000
The proliferation and invasion of low passage number human colon cancer cell lines is inhibited by retinoids
Authors: Martinez Marissa M. , Hurst Alexandra , Reynolds C. Patrick , Lane Michelle A. 
Published: November 2023

Previously we examined how vitamin A and its metabolite, all‐trans‐retinoid acid (ATRA), inhibit the proliferation and invasion of commercially available human colon cancer cell lines. Commercial cell lines may be suboptimal models, because they have been in culture for many passages. Our goal was to determine if low‐passage patient‐derived colorectal cancer cell lines (TX‐CC‐208 and TX‐CC‐286) also responded to retinoids. To determine if retinol and ATRA inhibited proliferation, 24 hours after seeding, cells were treated with 0 (vehicle control), 1, or 10 μM retinol or ATRA for 72 hours. TX‐CC‐208 cell number was decreased to 62.1 ± 3.1% of control regardless of retinoid type or concentration. Similarly, the number of TX‐CC‐286 cells was decreased to 51.8 ± 3.9 percent of control. TX‐CC‐208 cells were not invasive. The invasion of TX‐CC‐286 cells through Matrigel‐coated Boyden chambers was decreased to 40 ± 1.2% of control following 72 h of treatment with retinoids regardless of type or concentration. In conclusion, low‐passage (pass 7–17) patient‐derived colorectal cancer cell lines exhibited decreased proliferation and, in one cell line, invasion, in response to retinoid treatment. Both cells lines were sensitive to ATRA, suggesting they express retinoic acid receptors. These receptors are often not found in commercially available colon cancer cell lines, particularly invasive cell lines. These data suggest that retinol and ATRA may decrease the growth and metastasis of colon cancer in vivo. We are currently working to determine if ATRA mediates the ability of retinol to inhibit cell proliferation and invasion.Support or Funding InformationThis research was supported by donations from the Heather Custer Memorial Fund and Kiel Colon Cancer.
Greater Perseverance and Determination Predicts Lower Odds of Food Insecurity in Households with Children
Authors: Nikolaus Cassandra Jean , Schierer Megan Jean , Nickols‐Richardson Sharon M 
Published: November 2023

Food insecurity (FI), defined as the lack of access to culturally appropriate and adequate food to meet an individual's (or family's) needs, is often considered an international concern, but it continues to persist in developed countries. Diet quality and subsequent health of millions of American adults and children are threatened by household FI. Previous work has consistently established a negative relationship between household income and risk of FI. However, a small portion of households below the poverty line are able to maintain food security despite limited incomes. This has inspired researchers to investigate determinants, beyond income, that predict lower odds of household FI. The aim of this study was to investigate grit (a measure of two non‐cognitive traits: perseverance and determination) as a predictor of FI risk among a cross‐sectional sample of parents. An online questionnaire was designed to assess: 1) household FI using the 18‐item Household Food Security Survey Module; 2) perseverance and determination using the validated 8‐item Grit‐S questionnaire; and 3) several previously established predictors of FI (race, ethnicity, household size, education, marital status, health insurance, and income). This questionnaire was distributed to an online panel of U.S. consumers (Qualtrics LLC.). To be eligible, parents needed to have at least one child under the age of 18 years in the household and an overall household income below the 2015 median household income ($52,250 U.S. dollars per year). All statistical analyses were conducted using STATA/MP 14.1 (StataCorp LP); significance was set to α=0.05. Within the sample of n=252 parents, 61.1% reported household FI. Mean (±SD) Grit‐S was 3.35 (±0.62), on a scale of 1 (low grit) to 5 (high grit). Logistic regression was used to predict household FI from parent's Grit‐S score and established covariates. Overall, the model had a R2=0.08, and parent's Grit‐S score significantly decreased the odds of household FI (β= −1.12; 95% CI= −2.02, −0.23; P= 0.01); no other variables were significantly associated with FI. These results suggest that parent's perseverance and determination (as measured by Grit‐S) may be a valuable determinant of household FI. Future research should investigate whether these results are consistent when repeated in a larger and more diverse sample.Support or Funding InformationN/A
Consumption of whole aronia berry powder inhibits adoptive transfer‐induced colitis in mice
Authors: Pei Ruisong , Martin Derek , Bolling Bradley 
Published: November 2023

BackgroundAronia berries are rich in polyphenols which may inhibit inflammation by modulating gut immunocyte function. However, the mechanisms responsible for this effect is unclear.ObjectiveTo identify the effects of aronia consumption on intestinal inflammation and T cell populations in the mouse adoptive transfer model of colitis.DesignRecombinase activating gene (RAG)−/− mice were obtained at 4 wk age and were acclimatized for 2 weeks prior to experiments. Live CD4+CD45RBhigh cells were obtained by magnetic activated cell sorting (MACS) from gender and age‐matched syngeneic C57BL6 mice and transferred to RAG1−/− mice by intraperitoneal (IP) injection. Injected RAG1−/− mice were randomly assigned to receive a control or 4.5% w/w lyophilized ‘Viking’ aronia berry supplemented diet (n = 21/group). A negative control group of RAG−/− mice were injected with sterile phosphate‐buffered saline (PBS) as the sham group (n = 21). Body weight (BW) and food intake were recorded twice a week. Groups of mice were sacrificed at 7–8 wk post injection. Colons were collected for weight and length measurement. Lamina propria lymphocytes (LPL) and mesenteric lymph nodes (MLN) were isolated from colon and analyzed by flow cytometry to determine Th17 and Treg populations.ResultsBW declined at 4 weeks after CD4+CD45RBhigh transfer, and was accompanied by reduced food intakes. The aronia diet prevented colitic weight loss. Control BW decreased to 82.5% at wk 7, whereas the aronia‐fed mice decreased to 93.2% BW at wk 7. Intestinal inflammation was evident by noticeable increases in colon weight/length ratios compared to sham. Aronia consumption inhibited increases in colon weight/length ratios relative to the control (0.042 ± 0.008 vs. 0.058 ± 0.006 g/cm). MLN and LPL Treg populations in both groups of colitic mice did not differ from that in the sham. The total Th17 in LPL but not MLN was higher in aronia group than the control (P = 0.0216, n = 5–7/group).ConclusionWhole aronia berry consumption reduced wasting in T‐cell transfer‐induced colitis, and increased Th17 but not Treg populations in LPL.Support or Funding Information USDA NIFA AFRI WIS01909
Elevated Muscle Inflammatory Response After Protein‐Dense Food Ingestion in Obese Adults
Authors: Skinner Sarah K , Beals Joseph , Van Vliet Stephan , Niemiro Grace M , Dilger Anna C , De Lisio Michael , Paluska Scott , Burd Nicholas A 
Published: November 2023

Skeletal muscle inflammation related to alterations in the toll‐like receptor 4 (TLR4) signaling may lead to insulin resistance and poor muscle remodeling. However, the effect of food ingestion on modulating TLR4/ myeloid differentiation factor 88 (MyD88) signaling with or without excess fat mass has not been examined. Therefore, we examined skeletal muscle TLR4 and MyD88 protein content before and after protein‐dense food ingestion across a range of body mass indexes (BMIs) in healthy, sedentary adults. Eight healthy‐weight (HW: age; 25±1 y, BMI: 23.0±0.4 kg/m2, HOMA‐IR: 1.3±0.2), 8 overweight (OW: age; 25±2 y, BMI: 27.3±0.4 kg/m2, HOMA‐IR: 1.3±0.1), and 8 obese (OB: age; 29±3 y, BMI; 36.0±1.4 kg/ m2, HOMA‐IR: 6.1±0.8) men and women ingested 170 g of lean pork (36 g protein, 3 g fat). Repeated blood samples and muscle biopsies were collected from the vastus lateralis in the basal‐state and over a 5 h postprandial period. Plasma non‐esterified fatty acid (NEFA) concentrations declined during the postprandial period and these values did not differ between groups (P=0.61). Skeletal muscle TLR4 and MyD88 protein content were not different between groups at baseline (P>0.05). However, pork ingestion increased muscle TLR4 (1.9‐fold from baseline) and MyD88 protein content (1.6‐fold from baseline) (both P<0.05) in the OB group at 5 h of the postprandial period when compared to the OW and HW groups. These data show that food ingestion modulates the muscle inflammatory effect related to TLR signaling in obese adults, but not overweight and healthy weight adults, and appears to be independent of circulating plasma NEFA concentrations. The elevated muscle inflammatory response to food ingestion may, at least partly, contribute to the impaired postprandial glucose and protein handling commonly observed in obese adults.Support or Funding InformationThe National Pork Board
High‐Fat Diets Enriched with Varying Fatty Acid Compositions Have Differential Effects on Skeletal Muscle Troponin T pre‐mRNA Alternative Splicing
Authors: Black Adam , Schilder Ruud , Kimball Scot 
Published: November 2023

Alternative splicing (AS) of pre‐mRNA allows for a significant expansion of the proteome from a limited number of protein coding genes. Skeletal muscle Troponin T (Tnnt3) is known to be highly alternative spliced and expression of Tnnt3α splice forms in muscle has been shown to engender increased sensitivity to calcium‐induced muscle contraction and force production compared to Tnnt3β splice forms. We have previously shown that in the rat gastrocnemius, Tnnt3 AS is adjusted in a quantitative fashion in response to natural and experimental increases in body mass and these responses are impaired in obese rats. Therefore, the goal of the current study was to assess whether or not fatty acids or their downstream metabolites alter the pattern of Tnnt3 AS. In these studies, rats were fed either a 10% or 45% fat diet enriched with various types of fat (i.e. lard, saturated, mono‐, or poly‐unsaturated fats) for two‐weeks and the pattern of Tnnt3 AS in the gastrocnemius/plantaris complex was assessed. Rats fed high fat diets enriched with lard expressed significantly less Tnnt3α isoforms and more Tnnt3β isoforms compared to rats fed control lard diets. Rats fed high fat diets enriched with saturated fats had a similar trend in Tnnt3 AS. Interestingly, the high fat diet‐induced effects on Tnnt3 AS were not observed in rats fed diets enriched in mono‐or poly‐unsaturated fatty acids, suggesting that diets with varying fatty acid compositions have differential effects on Tnnt3 AS and that dietary saturated fatty acids may be driving this effect. To assess the possibility that saturated fat was acting directly on muscle to promote changes in AS, L6 myotubes were treated with either a saturated fat (palmitate), a monounsaturated fat (oleate), or a polyunsaturated fat (linoleate) for 24 h. Palmitate treatment caused a significant change in Tnnt3 AS as well as a 50% reduction in phosphorylation of Akt S473. In contrast, treatment with either oleate or linoleate had differential effects on Tnnt3 AS compared to palmitate treated myotubes and had no effect on Akt phosphorylation. Treatment with a downstream metabolite of palmitate, ceramide, had effects similar to palmitate on Tnnt3 AS and Akt phosphorylation. Moreover, co‐treatment with an inhibitor of ceramide biosynthesis attenuated the palmitate‐induced changes in AS. Overall, we show that varying the fatty acid composition of the diet can alter Tnnt3 AS and that in vitro fatty acids can directly and differentially alter Tnnt3 AS and signaling pathways important in skeletal muscle. Further elucidation of the environmental and intra‐ and extracellular signals regulating Tnnt3 AS will help us better understand the development of obesity induced muscle pathologies.Support or Funding InformationNIH (DK‐094141)
Energy intake during the Last Supper: Insights from Mathematical Models
Authors: Aselton Chris , Thomas Diana , Salinas Antonio 
Published: November 2023

BackgroundHistorical research and reliance on descriptions in the Bible provide insight into the kinds of foods that may have been consumed during the Last Supper. However, little is known regarding energy intake during this era.MethodsWe first applied historical food records to estimate the habitual energy intake. Using ancient Roman estimates of height from military recruitment records and life expectancy, we employed Waaler surfaces to algebraically back calculate body weight. A range of plausible PAL for males was derived from direct measurements in modern day agrarian cultures. Using the range of plausible physical activity levels (PAL) and estimated resting metabolic rate (RMR) from the Mifflin St. Jeor, Harris Benedict, and Livingston Kohlstadt models we derived lower and upper bounds for estimated habitual energy intake during the period of the Last Supper.ResultsFood records in the Mishnah tractate Ketubboth describes a minimum weekly diet for a woman when her husband was absent: two cobs of wheat (2.2 liters), half a cob of pulse (1.1 liters), half a log of oil (.5 liters), and one cob (1.1 liters) of dried figs or other fruit. A rough translation of these amounts into habitual daily intake averages to 1176 kcal/d. This estimate is below the cost to sustain life and implausible. Minimum height for Roman military recruits was approximately 163 cm and a rough estimate of height within the Roman army was 170 cm. Life expectancy was approximately 35 –45 years. Back calculation of the life expectancy from Waaler surfaces yielded a range of body mass index from 19–21 kg/m2. Range of weight was then computed to be 50.5 to 60.7 kg. The range of PAL obtained from Bolivian farmers was estimated between 1.65–2.51. The range of energy intake derived from the three different RMR models and ranges of PAL yielded daily intake as 2319 – 3973 kcal/d.ConclusionsHistorical records can provide information on what types of foods may have been consumed; however, the information is sparse and yields physiologically implausible values for habitual intake. The mathematical approach here can inform historical research by filling this gap.
Self‐reported Stress is Not Associated with Functional Magnetic Resonance Imaging Food‐cue Reactivity in Adults with Obesity
Authors: Quarles William R , Kahathuduwa Chanaka Nadeeshan , Davis Tyler , O'Boyle Michael , Binks Martin 
Published: November 2023

BackgroundPrevious studies have suggested that stress influences ingestive behavior in people with obesity. We hypothesized this may in part be influenced by heightened reactivity to food cues.ObjectiveTo examine the association between self‐reported levels of stress and brain functional magnetic resonance imaging (fMRI) food‐cue reactivity (FCR).MethodsBaseline data of 32 adults with obesity (age 19–65 yrs.; BMI 30–39.9kg/m2) was used from a larger study. Subjects rated their self‐reported perceived stress level in relation to household and work environments using 1–5 Likert‐scales (part of a larger demographic, health & weight history form). The subjects underwent an fMRI scanning session while rating 240 images (120 food and 120 objects) presented in an event‐related paradigm. Household and work environment stress scores were combined, and the mean of those scores was used to create a composite stress score. Subjects were then divided into two groups based on their composite stress score, using the median as the cutoff. FMRI analyses were conducted using FSL, in a three‐level model, to compare food‐cue reactivity of high vs. low stress groups. In separate analyses we compared high stress and low stress group associations with the following pre‐hypothesized regions of interest: amygdala, hippocampus, anterior cingulate cortex, orbitofrontal cortex, insula.ResultsFMRI analysis did not reveal any significant differences in FCR at the whole brain level or in pre‐hypothesize regions of interest.ConclusionWhile previous behavioral studies have suggested that stress influences ingestive behavior, we found no significant association of self‐reported stress with food‐cue reactivity in our sample of individuals with obesity. Therefore, our findings suggest that heightened food‐cue reactivity may not be a salient contributor to the previously noted relationship of stress to ingestion. However, further research is needed to more fully investigate the likely multidimensional contributors to this phenomenon.Support or Funding InformationFunding: Nestle Health Science.
Safety and Efficacy of a Novel Green Coffee Bean Extract (GCB‐70) in Overweight Subjects
Authors: BAGCHI DEBASIS , Verma Narsingh , Mittal Madhukar , Swaroop Anand , Bagchi Manashi , Preuss Harry G 
Published: November 2023

Obesity is now a worldwide epidemic and a novel natural therapeutic intervention is warranted. We have developed a novel, patent‐pending (PCT/IN2015/000236 dated 10th June 2015), water‐soluble green coffee bean extract, GCB‐70) enriched in 70% total chlorogenic acid including 45% caffeoylquinic acid and <1% caffeine in our laboratories. Our earlier studies demonstrated its novel antioxidant efficacy and its potential efficacy in weight management in rodents. This open‐labelled investigation evaluated the efficacy of GCB‐70 in 100 men and women overweight subjects (age: 18–65 years; body weight: 84.04 ± 1.46 kg) and BMI; 31.45 ± 4.49 kg/m2) over a period of 12 weeks. Institutional Review Board (IRB) and other institutional regulatory approvals were obtained for this study. This study was also registered in www.clinicaltrials.gov NCT02703025 Unique Protocol ID: Protocol #CR‐GCB‐ 70/ 07/14). Capsules (500 mg each, b.d.) were administered by the subjects 30–60 min prior to lunch and dinner. This study examined the body weight, BMI, WC and fasting glucose at 0, 4, 8 and 12 weeks of treatment. HbA1c, plasma leptin levels and thyroid stimulating hormone (TSH) were assessed at 0 and 12 weeks of treatment. Furthermore, extensive blood chemistry, adverse events, and physical health of the subjects were extensively evaluated to demonstrate the broad spectrum safety of GCB‐70. Body weight was reduced by 1.9%, 3.9% and 5.9% in male volunteers at 4, 8 and 12 weeks of treatment, respectively, while under these same conditions approximately 2.3%, 3.8% and 6.0% reductions were observed in female volunteers. BMI was reduced by 1.3%, 3.9% and 5.9% in male volunteers at 4, 8 and 12 weeks of treatment, respectively, while under these same conditions approximately 2.3%, 3.9% and 6.1% reductions were observed in female volunteers. Significant reductions in WC and fasting glucose were observed at these same time points in both male and female volunteers. HbA1c and plasma leptin levels were significantly reduced at 90‐days of treatments as compared to the corresponding baseline values, respectively. Blood chemistry data demonstrated the broad spectrum safety of GCB‐70. Overall, the results demonstrate that GCB‐70 is novel, safe and low caffeine antioxidant supplement effective in healthy weight management.Support or Funding InformationThe Study Was Funded by Cepham Inc, Piscataway, NJ