bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Disease Symptoms are Reduced in C57BL/6J Mice Fed High‐fat Diets Supplemented with Oak Tannins
Authors: Shay Neil F , Luo Ting F , Sturm Marlena F 
Published: November 2023

Previous work has demonstrated that moderate red wine consumption, and intake of some bioactive compounds in wine including quercetin and resveratrol correlate with a reduced incidence of metabolic disease symptoms. The aging of wine in oak barrels adds to the polyphenolic content of wine by introducing oak tannins to the wine. Tannins have been suggested to be related to the hypothesized beneficial effect of wine against the progression of cardiovascular and metabolic disease.The objective of the present study is to investigate the influence of oak tannin intake on the symptoms of metabolic syndrome induced by the consumption of a high fat diet fed C57BL/6J (C57) mice. C57 mice were fed low fat (LF), high fat (HF), and HF containing 0.16% (w/w) of oak tannin powder (HF+OT) for 10 weeks. HF + OT intake significantly reduced body weight (42.4g±1.2g [HF] vs. 38.2g±1.4g [HF+OT]). Glucose homeostasis was regulated by OT intake, e.g., serum resistin levels were lower in HF+OT‐fed mice, compared to HF‐fed mice (374±11 pg/mL in HF vs.301±10 pg/mL). Further, hepatic lipid accumulation was lower in the HF+OT‐fed group (p<0.05). To further understand the underlying mechanisms of how OT intake regulates glucose and lipid metabolism, hepatic gene expression related to lipid, glucose, and xenobiotic metabolism was evaluated. Relative expression of Gstm2 was significantly decreased in the HF+OT group (p<0.05). Scd1 gene expression was increased in the HF‐fed group, and reduced to a value resembling the LF‐fed group in HF+OT fed mice. Nqo1 and Cyp2b10 gene expression was decreased with OT intake. Serum levels of the pro‐inflammatory cytokine MCP‐1, was marginally reduced HF+OT‐ vs. HF‐fed mice (p=0.0877).A follow‐up study was completed to determine whether the consumption of oaked vs. unoaked red wine can influence metabolic syndrome parameters in HF‐fed mice. In a ten‐week trial, mice were fed LF or HF diets, and HF diets with an oaked wine concentrate (HF+OWC) or unoaked wine concentrate (HF+UWC). Intake of both the HF+OWC and HF+UWC reduced body weight gain, compared to HF‐fed mice. Hepatic gene expression evaluation of Lipe, Cyp2b10, and Gsta showed more significant regulation of these mRNAs with intake of OWC vs. UWC.We conclude that intake of oak tannins have the potential to act as an agent to ameliorate symptoms of metabolic syndrome.Support or Funding InformationDesert Heart Foundation
Muscadine Grape Extract Inhibits Proliferation and Migration of Triple Negative Breast Cancer Cells in Association with a Reduction in TWIST
Authors: Collard Marianne , Gallagher Patricia E. , Tallant Ann 
Published: November 2023

Muscadine grape (V. rotundifolia) seeds and skins are used as nutraceuticals for their anti‐oxidant, anti‐inflammatory and anti‐cancer properties. However, the effect of treatment with muscadine grapes on different types of cancers, including breast cancer, is limited. Triple negative breast cancer is a subtype of breast cancer which is characterized by the lack of estrogen receptors, progesterone receptors and over‐expression of the epidermal growth factor receptor, limiting targeted treatment for women with the disease. In addition, triple negative breast cancer which disproportionally affects ethnic minorities and younger women has a high propensity to metastasize, rendering it one of the more aggressive breast cancer subtypes. The goal of this project was to determine whether a proprietary muscadine grape extract (MGE; from Piedmont Research & Development Corp.) reduces the growth and metastatic progression of triple negative breast cancer. A dose‐ and time‐dependent decrease in proliferation was observed following MGE treatment of murine 4T1 cells (83.3% inhibition at 25 μg/mL for 24 h; n=3, p < 0.01) and human MDA‐MB‐231 (49.4% inhibition at 25 μg/mL for 48 h; n=3, p < 0.001), BT‐549 (46.0% inhibition at 25 μg/mL for 48 h; n=3, p < 0.001) and BT‐20 (43.6% inhibition at 25 μg/mL for 48 h; n=3, p < 0.001) triple negative breast cancer cells as compared to untreated cells. MGE also reduced the migration of triple negative breast cancer cells measured using a scratch wound assay. The significant reduction in migration of 4T1 (220.9 ± 16.6 μm vs 44.0 ± 6.2 μm at 25 μg/mL for 12 h; n=3, p < 0.001), MDA‐MB‐231 (549.2 ± 53.5 μm vs 268.3 ± 41.5 μm at 25 μg/mL for 18 h; n=3, p < 0.01) and BT‐549 (424.4 ± 40.7 μm vs 140.3 ± 33.6 μm at 25 μg/mL for 36 h; n=3, p < 0.01) cells by MGE was dose‐ and time‐dependent as well as independent of proliferation.The transcription factor TWIST, which is involved in the epithelial‐to‐mesenchymal transition, is critical in the development of metastasis due to the increased migration and invasion of cancer cells exhibiting the mesenchymal phenotype. MGE significantly reduced TWIST expression at a concentration of 20 μg/mL in 4T1 triple negative breast cancer cells with a maximal decrease of 64.6% compared to untreated cells after 12 h of treatment (n = 5; p < 0.05). Furthermore, phospho‐ERK1/2, a MAP kinase which positively regulates TWIST, was reduced approximately 2‐fold (n = 5; p < 0.05) after 10 h of 20 μg/mL MGE treatment or greater than 3‐fold (n = 6; p < 0.05) after 12 h. Taken together, these results suggest that MGE reduces ERK1/2 activities to down‐regulate TWIST and inhibit the migration of triple negative breast cancer cells, and that treatment with MGE may be an effective therapeutic to decrease the progression of triple negative breast cancer and prevent metastasis at distant sites.
Monomeric cocoa procyanidins enhances β‐cell function by increasing mitochondrial respiration
Authors: Tessem Jeffery Sivert , Rowley Thomas J. , Bitner Benjamin F. , Ray Jason D. , Smithson Andrew T. , Hansen Jason M , Bikman Benjamin T. , Neilson Andrew P 
Published: November 2023

A hallmark of type 2 diabetes (T2D) is β‐cell dysfunction and the eventual loss of functional β‐cell mass. Therefore, mechanisms that can improve β‐cell function could be used as a treatment for the millions of individuals with T2D. Recent studies have shown that monomeric, oligomeric and polymeric cocoa derived procyanidins have vastly different effects on obesity, insulin resistance and glucose tolerance during high fat feeding. Based on these previously published data, we hypothesized that cocoa derived procyanidins may have beneficial effects on improving β‐cell function. 832/13 INS‐1 derived β‐cells and primary rat islets cultured with monomeric cocoa procyanidins demonstrated enhanced glucose stimulated insulin secretion (GSIS), while cells cultured with total cocoa extract, oligomeric procyanidins or polymeric procyanidins demonstrated no improvement. The increased GSIS observed with culture in the presence of monomeric procyanidin fractions corresponded with enhanced mitochondrial respiration, suggesting improvements in β‐cell fuel utilization. We demonstrated upregulation of electron transport chain components Complex III, IV and V after culture with monomeric procyanidins. Monomeric procyanidins also resulted in an increased cellular redox state and increased glutathione concentration, which corresponds with Nrf2 nuclear localization. We propose a model by which cocoa derived monomeric procyanidins enhance the cellular redox state, allowing Nrf2 to migrate to the nucleus and enhance expression of key mitochondrial genes that results in enhanced GSIS and improved β‐cell function. These results suggest that cocoa derived monomeric procyanidins could be leveraged as a treatment modality for patients with T2D.Support or Funding InformationBYU MEG Grant to JST, Diabetes Action Research and Education Grant to JST, BYU ORCA Grant to JDR and BFB
Altered Postprandial Lipemia and Fatty Acid Handling in Obese vs. Normal‐Weight Men Is Rectified by Reducing Dietary Fat Load: A Dose‐Response Trial
Authors: Vors Cécile , Gabert Laure , Drai Jocelyne , Louche‐Pélissier Corinne , Laville Martine , Vidal Hubert , Michalski Marie‐Caroline 
Published: November 2023

BackgroundPostprandial hyperlipemia and altered dietary lipid beta‐oxidation are now recognized as metabolic risk factors in obesity that are directly associated with dietary fat intake. The amount and size of chylomicrons are known to impact their clearance and thus possibly modulate the final partitioning of dietary fatty acids (FA) between β‐oxidation and storage, which is altered in obesity. However, the detailed impact of ingested fat amount on postprandial lipemia and dietary FA fate in obese subjects remains to be elucidated.MethodsIn a randomized crossover study, eighteen healthy normal‐weight (NW) and obese men ingested meals containing 10g or 40g of fat (typical breakfast fat contents) labeled with a mix of 13C‐triglyceride tracers. Chylomicron triglyceride content and size were measured during 8h of digestion. Plasma concentrations of 13C‐palmitate and 13C‐oleate were also measured during 8h in parallel with their fecal loss (72h‐stool collection). 13CO2 breath‐test coupled to indirect calorimetry measures during 8h allowed to calculate exogenous lipid fate.ResultsChylomicron triglycerides increased in all subjects according to ingested fat amount (P<0.01). After 40g of fat, obese men had delayed postprandial lipemia compared to NW men (PtimexBMI<0.0001) especially at 5–8h post‐breakfast (P<0.01), with different variations in chylomicron size (PtimexBMI<0.01). This was associated with a lower appearance of tracers in plasma in obese men (P<0.01 for AUC 0–5h vs. NW), and a tendency to higher fecal excretion of 13C‐oleate (P=0.1 vs. NW) after 40g of fat. However after 10g of fat, chylomicron TG and size, and tracer kinetics and fecal loss, were similar regardless of BMI. Finally, the impact of fat amount on exogenous lipid β‐oxidation was different according to BMI (PdosexBMI<0.01): 39.6% of ingested lipids were β‐oxidized after 40g of fat in obese (vs. 45.1% in NW) but this was increased to 53.1% in obese for 10g of fat (vs. 49.7% in NW subjects; P<0.001 vs. 40g).ConclusionsPostprandial lipemia profile after a realistic high‐fat load is altered in obese subjects. Although the reduction of ingested fat amount seems to normalize the postprandial fate of dietary lipids in obese men, further research is needed to understand mechanisms of altered postprandial lipid metabolism in obesity.Support or Funding InformationThe Study was funded by CNIEL (French Dairy Interbranch Sector) and INRA (French National Institute for Agricultural Research).
Dietary Cholesterol Contained in Whole Eggs is Not Well Absorbed and Does Not Affect Plasma Total Cholesterol Concentration in Men and Women: Results from Two Randomized Controlled Crossover Trials
Authors: Kim Jung Eun , Campbell Wayne W 
Published: November 2023

Whole egg is a well‐known food source of dietary cholesterol and inconsistent research findings exist about the effect of dietary cholesterol from whole egg on blood cholesterol concentration. A previous animal study reported that phosphatidylcholine in egg yolk inhibits dietary cholesterol uptake by the intestine. Therefore, in this study, we assessed the effect of co‐consuming cooked whole eggs on dietary cholesterol absorption in adults from 2 randomized controlled crossover trials.For study 1, 16 men (mean ± SE; age: 24 ± 1 y; BMI: 24 ± 1 kg/m2) consumed a raw mixed vegetable salad (0 mg dietary cholesterol) with no egg, with 75 g cooked whole egg (CWE) (280 mg dietary cholesterol), or with 150 g CWE (560 mg dietary cholesterol). For study 2, 17 women (age: 45 ± 4 y; BMI: 25 ± 2 kg/m2) consumed cooked mixed vegetables (0 mg dietary cholesterol) with no egg or with 100 g CWE (373 mg dietary cholesterol). In both studies, blood was collected hourly for 10 hours and triacylglycerol‐rich lipoprotein (TRL) fractions were isolated. Total cholesterol and triacylglycerol concentrations in TRL fractions and plasma were analyzed and composite areas under the curve (AUCs) were calculated. Concentrations of total cholesterol and triacylglycerol within TRL fractions represent newly absorbed cholesterol and triacylglycerol.In study 1, total cholesterol AUC0–10h in TRL fractions was not different among 150 g CWE vs. 75 g CWE vs. no egg (lsmean ± SE; 5.3 ± 1.2 vs. 4.2 ± 1.2 vs. 1.7 ± 1.2 mg • dL−1 • 10h, p = 0.11) but triacylglycerol AUC0–10h in TRL fractions was greater for 150 g CWE vs. 75 g CWE and no egg (79 ± 12a vs. 21 ± 12b vs. 13 ± 12b mg • dL−1 • 10h, p = 0.0005). Similarly, in study 2, total cholesterol AUC0–10h in TRL fractions was not different between 100 g CWE vs. no egg (5.2 ± 0.9 vs. 3.8 ± 0.9 mg • dL−1 • 10h, p = 0.30) but triacylglycerol AUC0–10h in TRL fractions was greater for 100 g CWE vs. no egg (31 ± 3a vs. 11 ± 3b mg • dL−1 • 10h, p < 0.0001). In both studies, plasma total cholesterol AUC0–10h was not affected by egg consumption (23 ± 13 vs. 20 ± 13 vs. 22 ± 13 mg • dL−1 • 10h, p = 0.92; 50 ± 11 vs. 43 ± 11 mg • dL−1 • 10h, p = 0.65), while triacylglycerol AUC0–10h was increased (207 ± 36 vs. 66 ± 36 vs. 66 ± 36 mg • dL−1 • 10h, p = 0.0097; 125 ± 23 vs. 50 ± 23 mg • dL−1 • 10h, p = 0.0257) when subjects consumed more eggs that contain greater amounts of dietary cholesterol and triacylglycerol.Collectively, these findings support that the dietary cholesterol found in whole eggs was not well absorbed and did not affect plasma total cholesterol concentration, although whole egg contains high amount of dietary cholesterol. Thus, increased intake of dietary cholesterol from eggs may not indeed raise the blood cholesterol concentration.Support or Funding InformationSupport: American Egg Board‐Egg Nutrition Center; NIH UL1TR001108; Purdue Ingestive Behavior Research Center
Intake of up to Three Eggs per Day is Associated with Improvements in Markers of HDL Function and Antioxidant Capacity in a Young, Healthy Population
Authors: DiMarco Diana M , Norris Gregory H , Millar Courtney L , Blesso Christopher N , Fernandez Maria Luz 
Published: November 2023

Recent evidence suggests that the composition and function of HDL particles may be more important than HDL cholesterol concentration when assessing risk for cardiovascular disease (CVD). HDL is involved in reverse cholesterol transport, the process by which excess cholesterol is removed from tissues and returned to the liver for biliary excretion. In addition to transporting cholesterol, HDL particles carry antioxidant proteins, enzymes, and carotenoids, all of which help protect against oxidative damage to both HDL and LDL particles. Eggs contain cholesterol and carotenoids and therefore may impact CVD risk by modulating lipoprotein composition and function. The goal of this research was to determine the impact of intake of up to 3 eggs/d on LDL and HDL particle size, function, and associated antioxidants in a young, healthy population. Thirty‐eight healthy individuals (19 men/19 women, 24.1 ± 2.2 y, BMI 24.3 ± 2.5 kg/m2) completed this 14‐week crossover dietary intervention. Qualifying participants underwent a 2‐week washout (0 eggs/d), followed by intake of 1, 2, and 3 eggs/d for 4 weeks each. Following each dietary period, fasting plasma and serum were collected for analysis of lipoprotein particle size and subfractions by nuclear magnetic resonance and concentrations of plasma apolipoproteins and carotenoids (lutein and zeaxanthin). Activities of plasma cholesteryl ester transfer protein (CETP) and lecithin‐cholesterol acyltransferase (LCAT) were assessed using fluorometric kinetic assays. Lastly, serum paraoxonase‐1 (PON1) activity toward phenyl acetate was measured using an in‐house kinetic assay. Compared to 0 eggs/d, intake of 1–3 eggs/d led to increased large LDL and large HDL particle concentrations (p < 0.05), a 9–20% increase in plasma apoA‐I (p < 0.05), and increased LCAT activity (p < 0.05). Furthermore, as compared to 0–1 eggs/d, intake of 2–3 eggs/d resulted in an 11% increase in apoA‐II (p < 0.05) and a 20–31% increase in plasma lutein + zeaxanthin (p < 0.05). Lastly, as compared to lesser quantities of eggs, intake of 3 eggs/d led to increased serum PON1 activity (p < 0.05). In contrast, egg intake had no impact on plasma CETP activity. In summary, intake of 1 egg/d appears sufficient to increase large LDL particle concentration and biomarkers associated with HDL function. However, intake of 2–3 eggs/d supports greater improvements in markers of HDL function and antioxidant capacity. Overall, intake of up to 3 eggs/d improves these biomarkers associated with lipoprotein function and CVD risk in a young, healthy population.Support or Funding InformationThis research was supported by an award to MLF from the Esperance Family Foundation and a grant to DMD from the Egg Nutrition Center.
How to create interactive digital resources that result in real learning outcomes
Authors: Rea Paul , Krebs Claudia 
Published: November 2023

Over recent years, technological advances and digital tools in anatomical education have been rapidly developing. Indeed, the way our students learn and access educational resources has changed significantly over the years. This is also reflected in the surge to the market of digital educational material, and not always validated by professional anatomists.Through an International Anatomy Education Hub, we have combined our skillsets in the field of digital anatomy from anatomy and surgical staff, from four leading universities across the globe. We aim to introduce a variety of tools and software that we as educators, and student users, could use in generating educationally validated, curriculum specific, digital anatomical training materials.Based on human‐computer interaction research and theories, evidence‐based guides to building effective educational content in the digital environment will be discussed. It will also highlight strategies for involving the students as co‐creators of educational materials, designing assessment tools, and will present feedback from the end user.Simple and effective ways to build local, curriculum specific content, in an open source format, will be presented, as well as the benefits of international collaborations. This will show how local digital focused activities can benefit the global anatomical education community.
The Influence of Dietary Micronutrients Upon the Risk of ‘Pouchitis’‐like Inflammation in Genetically Susceptible Hosts
Authors: Pierre Joseph F. , Hinterleitner Reinhard , Bouziat Romain , Hubert Nate , Miyoshi Jun , Jabri Bana , Chang Eugene B 
Published: November 2023

Ulcerative colitis (UC) is a subset of inflammatory bowel disease (IBD) characterized by inflammation in the colon, but not small bowel. In medically refractory UC, the ultimate treatment is total proctocolectomy and surgical creation of an ileal pouch. Unfortunately, many IBD patients develop inflammation within the pouch, termed ‘pouchitis’. Gut dysbiosis, host genetics, and environmental triggers are implicated as causative factors in IBD, yet mechanisms are poorly understood. Following observations that diet may influence inflammatory risk, we employed our newly established murine model of ‘pouchitis’ – using surgically created ileal self‐filling loops ‐ to investigate the role of dietary micronutrients upon disease risk in genetically susceptible hosts. C57B/6 WT and IL‐10−/− mice were randomized to Control (CON) or Antioxidant (AOX) diet ‐ containing pharmacologically relevant levels of 4 micronutrients – for two weeks following surgical recovery. There were no differences in body weight change or survival; however, IL‐10−/− CON animals had significantly larger lymphoid organs compared with IL‐10−/− AOX or WT mice on either diet. Examination of IL‐10−/− CON loop mucosa demonstrated histological inflammation characterized by goblet cell depletion, increased tissue MPO levels, and elevated IFN‐γ, TNFα, and IL‐17α expression, which was attenuated with AOX. There were no difference in luminal IgA between diets in eiher genotype; however, compared with IL‐10−/− CON mice, AOX mice had significantly greater CD45+CD4+FOXp3+ Treg cells and fewer CD45+CD4+RORg T cells, without changes in CD45+CD4+T‐bet cells. 16S analysis demonstrated AOX increased the Bacteriodetes‐to‐Firmicutes ratio and increased alpha diversity compared with CON diet in both genotypes. Importantly, convention alization of germ‐free IL‐10−/− with CON derived microbes, but not AOX microbes, recapitulated the inflammatory phenotype. These experiments demonstrate the ability of common dietary components to mitigate intestinal inflammatory disease in genetically susceptible hosts and highlight the role of microbial populations in disease pathogenesis. Using this model, further elucidation of immune‐microbial compartment set points that occur under specific dietary components may help us understand, and eventually avoid, dietary factors that result in recurrent inflammatory episodes in susceptible pouchitis patients.Support or Funding InformationThis work was supported by NIH NIDDK F32DK105728‐01A1, P30DK42086.
Combination of Quercetin and Green Tea Extract Increased Plasma Epicatechingallate and Decreased Urine Epigallocatechin and Epicatechin Concentrations
Authors: Henning Susanne M , Aronson William J , Wang Piwen , Wang Jieping , Lee Ru‐Po , Grojean Emma M , Ly Austin , Hsu Mark , Heber David , Li Zhaoping 
Published: November 2023

Preclinical studies have shown that the combination of quercetin (Q) and green tea (GT) extract enhanced the anti‐carcinogenic activity in a prostate cancer xenograft model, increased the bioavailability of GT polyphenols (P) and decreased P methylation compared to GT extract alone. In order to test the hypothesis in humans that Q in combination with GT extract would enhance bioavailability of GTP compared to GT extract consumption alone we enrolled 32 men diagnosed with prostate cancer and randomized them to receive 2 capsules of GT extract (240 mg) in combination with either 1 capsule of Q (400 mg) (GT+Q) or placebo (GT+PL) two times per day prior to prostatectomy. Blood and early morning spot urine were collected at baseline and at 3 weeks. Bioavailability of GTP and Q were tested at 3 weeks by sampling before and 2 hours after administration of GT and Q. Immediately after the surgery a small aliquot of prostate tissue was collected. All urine, blood and tissue samples were analyzed for GTP and Q by high performance liquid chromatography with coularray detection and mass‐spectrometry. Red blood cell (RBC) and prostate gene expression, protein expression and DNA and polyphenol methylation enzyme activity were determined. There was no liver toxicity in any subject. Q was increased 14‐fold, 12‐fold and 4.5‐fold in plasma, urine, and prostate tissue, respectively, in subjects given GT+Q by comparison to GT+PL. Plasma ECG was significantly increased in men consuming GT+Q compared to GT+PL consistent with an effect of Q on bioavailability of GT as previously observed in animals. Urinary excretion of EGC, 4'‐MeEGC and EC was significantly decreased in urine collected prior to surgery in participants consuming GT+Q compared to GT+PL. The percent of methylated EGC tended to increase from 36 to 79% in urine from men consuming GT+Q compared to GT+PL (p=0.137). ECG and/or EGCG were found in the prostate tissue of 31 out of 32 participants, but there was no difference in prostate GTP content between the GT+Q and GT+PL groups. There were also no epigenetic differences in prostate or RBC as determined by catechol‐methyltransferase and DNA‐methyltransferase gene and protein expression and enzyme activity. Further investigations are underway to determine whether the presence of quercetin in addition to GT polyphenols in the prostate modulated inflammation or oxidant stress in prostate tissue.Support or Funding InformationNIH RO3CA171583