bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic flavan‐3‐ol exposure induces changes in metabolism and transport kinetics in differentiated Caco‐2 cell monolayers (270.1)
Authors: Redan Benjamin , Ferruzzi Mario 
Published: June 2021

A limiting factor in the application of flavan‐3‐ols for chronic disease prevention is their low oral bioavailability. However, evidence suggests that chronic dosing paradigms can significantly increase their bioavailability. To explore fundamental alterations occurring from chronic gut exposure to flavan‐3‐ols, Caco‐2 monolayers were cultured and differentiated in 6‐well plates in addition to Transwell® inserts for 12 and 21 days, respectively. Culture media contained 0, 1, or 10 μM concentrations of epigallocatechin gallate (EGCG) or epicatechin (EC). Following differentiation, cellular uptake and transport of flavan‐3‐ols was assessed from 0‐6 h following a final 50 μM acute treatment of respective pretreated compound. Transport of flavan‐3‐ols, along with metabolism to methylated and sulfonated metabolites, was assessed by LC‐TOF‐MS. After 90 min, 1 μM EGCG pretreated monolayers showed significantly (P < 0.05) greater accumulation compared to control (mean ± SEM; 310. ± 12.4 vs. 208 ± 12.1 pmol EGCG/mg protein). 1 μM EC pretreatment showed similar significant (P < 0.05) results (477 ± 65.9 vs. 150. ± 35.0 pmol EC/mg protein). Further, Papp calculated from Transwell® experiments for 10 μM pretreated cell monolayer were 7.93 x 10‐7 cm/s compared to 5.09 x 10‐7 cm/s for control. These results suggest that intestinal transport and metabolism of flavan‐3‐ols is modulated by chronic exposure.Grant Funding Source: Supported by National Science Foundation Graduate Research Fellowship Program Grant No. DGE‐1333468.
Pharmacokinetics and brain distribution of polyphenols from fruit extracts in young pigs (270.2)
Authors: Janle Elsa , Chen Tzu‐Ying , Kritchevsky Janice , Hargett Katherine , Feller Kathryn , Klobusnik Ryan , Tabaczyk Olivia , Ferruzzi Mario , Jouni Zeina 
Published: June 2021

To assess the bioavailability and brain accretion of dietary polyphenols, pigs (14 ± .5 lb) were divided into 5 groups (n=8/group) of control (water), low (27.5 mg/kg) or high (82.5 mg/kg) concentration of bilberry extract or apple/grape seed extract (A/GSE). Polyphenol ingredients were delivered once a day. After 3 weeks, a plasma 24h pharmacokinetic study was conducted. Blood and brain regions (stem, cerebellum, cortex, hypothalamus, hippocampus and amygdala) were harvested 24 h later and analyzed for key polyphenol metabolites from (epi)catechin, quercetin and anthocyanins by HPLC‐MS/MS. Polyphenols were not detected in control plasma or brain samples. A significant (p <.05) plasma dose response was observed for epicatechin and catechin metabolites in the A/GSE groups. Most of the plasma anthocyanin metabolites in bilberry groups exhibited significant or trend (0.05 < p < 0.1) dose responses. Brain accumulation varied (in pmol/g tissue): (epi)catechin (7‐1430), quercetin (0.1‐1.2), anthocyanins (0‐3). Significant differences were observed between different brain regions and not all metabolites were detected in all brain regions. The highest concentration for most metabolites was in the cerebellum in both high concentration groups. These data demonstrate that polyphenol metabolites can cross the blood‐brain barrier and accumulate at different concentrations in different brain regions. Grant Funding Source: Supported by Mead Johnson Nutrition
Ellagic acid attenuates adipocyte differentiation via histone arginine methylation‐associated epigenetic modification (271.2)
Authors: Kang Inhae , Okla Meshail , Chung Soonkyu 
Published: June 2021

Previously, we have demonstrated that ellagic acid (EA), a naturally occurring polyphenol in numerous fruits and vegetables, represses adipogenic conversion of human adipose‐derived stem cells (hASCs) by altering epigenetic factors. However, the detailed mechanism by which EA attenuates adipocyte differentiation is largely unknown. In this study, we first hypothesized that upregulation of HDAC9 by EA is the key mechanism to inhibit adipogenesis. Unexpectedly, knockdown HDAC9 by siRNA had marginal impact on recovering adipogenesis. Intriguingly, EA treatment was associated with reduced histone 3 arginine 17 methylation levels (H3R17me2), implying the inhibitory role of EA in CARM1 (coactivator associated arginine methyltransferase 1) activity. To test the hypothesis that recovery of H3R17me2 will rescue EA‐mediated inhibition of adipogenesis, cell‐penetrating peptides of CARM1 (CPP‐CARM1) was delivered to compensate the loss of CARM1 activity by EA. Delivery of CPP‐CARM1 was able to restore H3R17me2, HDAC9 dissociation, histone acetylation levels, PPARγ expression, and triglyceride accumulation. Taken together, our data suggest that reduced CARM1 activity by EA results in a decrease of H3R17me2 levels, which may interrupt consecutive histone remodeling steps for adipocyte differentiation including histone acetylation and HDAC9 dissociation from chromatin.Grant Funding Source: Supported by USDA‐HATCH
Folate in a high multivitamin gestational diet causes obesogenic phenotype and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring (271.3)
Authors: Cho Clara E. , Pannia Emanuela , Huot Pedro S.P. , Sánchez‐Hernández Diana , Kubant Ruslan , Bazinet Richard P. , Anderson G. Harvey 
Published: June 2021

High multivitamin (HV, 10‐fold AIN‐93G) gestational diets fed to Wistar rats produce offspring with higher food intake, obesity and characteristics of metabolic syndrome. The objective was to determine if folate within the HV diet contributes to obesogenic phenotype through epigenetic effects on hypothalamic regulatory mechanisms. Male offspring of dams fed HV diet with normal folate (NF) (HVNF) were compared with those from HV fed dams. Offspring were weaned to a high fat diet for 8 weeks. HVNF offspring had lower food intake (5%, P=0.0005), body weight (4%, P=0.03), fat preference (12%, P=0.02), adiposity index (10%, P=0.04), plasma leptin concentration (24%, P=0.03), glucose response to a glucose load (18%, P<0.05) and insulin resistance (12%, P=0.03). They had higher pro‐opiomelanocortin (POMC; 38%, P<0.05) and lower leptin receptor (Ob‐Rb; 10%, P=0.03), mammalian target of rapamycin (MTOR; 7%, P=0.01), serotonin receptor (5‐HTR) 1A (11%, P=0.03) and 5‐HTR2A (21%, P=0.03) gene expression. DNA methylation of 5‐HTR1A (P=0.0007) was lower but higher in 5‐HTR2A (P=0.01). Phosphoinositide 3‐kinase (PI3K) signaling protein expression was improved (42%, P=0.03). In conclusion, folate in the HV gestational diet contributes to the obesogenic phenotype in the offspring concurrent with alterations in gene expression, DNA methylation and energy sensing in the hypothalamus that favor increased food intake.Grant Funding Source: Supported by Canadian Institutes of Health Research, Institute of Nutrition, Metabolism and Diabetes
Quantity of dietary protein, but not pattern of intake, affects net protein accretion in older adults (272.4)
Authors: Kim Il‐Young , Schutzler Scott , Wolfe Robert , Ferrando Arny 
Published: June 2021

We examined 16‐h whole body protein turnover [protein synthesis (PS), breakdown (PB), and net balance (NB), expressed as delta changes from the fasted state] in four permutations: a level of protein intake of 0.8g/kg/day (1RDA) or 1.5g/kg/day (2RDA) with an uneven [U: 15/20/65%)] or even distribution patterns of intake (E: 33/33/33%) for breakfast, lunch, &amp; dinner of intake over the day. Twenty healthy older subjects were randomly assigned into one of 4 groups: 1RDA‐U, 1RDA‐E, 2RDA‐U, or 2RDA‐E, and were studied with primed continuous infusions of ring‐[2H5]phenylalanine &amp; ring‐[2H2]tyrosine on day 4 following 3 days of diet habituation. Positive NB was achieved at both protein levels, but NB was significantly greater in 2RDA vs. 1RDA [NB: 94.75 ± 6.01 vs. 58.86 ± 4.91 g protein/kg/750min; p = 0.0001], without effects of distribution on NB. The greater NB was due to the higher PS with 2RDA vs. 1RDA [PS: 15.40 ± 4.84 vs. ‐17.98 ± 8.44 g protein/kg/750min; p = 0.0018]. PS was significantly correlated with delta changes of mean plasma concentrations of leucine from the fasted state (R2 = 0.51, p = 0.0004). We conclude that in the context of mixed meals whole body net protein accretion is greater with protein intake above recommended dietary allowance (0.8 g protein/kg/day), regardless of protein intake pattern, primarily through increased protein synthesis.Grant Funding Source: Supported by Dairy Research Institute and Award Number UL1TR000039 and KL2TR000063 (NCATS and NIH)
The addition of non‐fat dairy products to the regular diet reduces central blood pressure and improves vascular function (272.5)
Authors: Machin Daniel , Park Wonil , Alkatan Mohammed , Mouton Melissa , Tanaka Hirofumi 
Published: June 2021

Elevated central systolic blood pressure and vascular dysfunction increase the risk of cardiovascular disease. Using a randomized, crossover study design, we tested the hypothesis that the addition of non‐fat dairy products to the regular diet would reduce carotid systolic blood pressure (cSBP) and improve vascular function. Forty‐four adults with elevated brachial blood pressure (52±2 yr, 133±1/80±1 mmHg) underwent a high dairy condition (+4 servings/day non‐fat dairy products) and isocaloric non‐dairy condition (+4 servings/day fruit products) in which all dairy products were removed. Both dietary conditions lasted four weeks with a 2‐week washout before crossing over. After the high dairy condition, cSBP decreased, brachial flow‐mediated dilation (FMD) increased, and carotid‐femoral pulse wave velocity (cfPWV) decreased (‐3±1mmHg, +1.1±0.5%, ‐66±18 cm/sec, respectively; p<0.05). After the non‐dairy condition, cSBP or cfPWV did not change, but FMD was reduced (‐1.0±0.5%, p<0.05). ∆cSBP was positively related to ∆cfPWV (r=0.59). In conclusion, the addition of non‐fat dairy products to the regular diet reduced central systolic blood pressure and improved vascular function. Additionally, the hypotensive effects of non‐fat dairy products may in part be mediated by reductions in central arterial stiffness.Grant Funding Source: Supported by Dairy Research Institute
Potentiation of TNF‐induced inflammatory transcriptional regulation by SFK activation (278.3)
Authors: Adam Alejandro , Lu Yao Wei , Alsaffar Hiba , Martino Nina , Lowery Anthony , Schwarz John , Vincent Peter 
Published: June 2021

TNF induces dramatic changes in the transcriptional profile of endothelial cells to promote a pro‐inflammatory phenotype that allows leukocyte transendothelial migration and loss of barrier function. We have previously shown that treatment with 50 pg/ml TNF increases endothelial permeability after 4‐6 h in monolayers of human dermal microvascular endothelial cells expressing DN‐Csk to activate endogenous Src Family Kinases (SFKs) but not in control (LacZ) monolayers. We thus reasoned that this delay in increasing permeability could be due to a requirement in transcriptional changes. Here, we demonstrate that activation of SFKs potentiates the transcriptional effects induced by TNF. After 6 h, TNF elevated ICAM1, E‐Selectin, HSPA1A/B and complement C3 mRNA levels 41‐, 76‐, 12‐ and 24‐fold respectively. In the presence of DN‐Csk, the same treatment induced these genes 149‐, 310‐, 38‐ and 202‐fold, respectively. Similar effects were observed in the mRNA of TNF itself (46 vs 193 fold) and lymphotoxin A (5 vs 21 fold), but not lymphotoxin B (86 vs 83 fold). ATF3 was induced 7 and 20‐fold respectively. EGR2 mRNA was induced 5‐fold by DN‐Csk and 9‐fold by the dual treatment, while Fos mRNA was induced 4‐fold in DN‐Csk‐expressing cells after 6h TNF and 9‐fold after 18 h. While these treatments did not lead to changes in the expression of many junctional genes, ZO‐1 and VE‐cadherin localization was drastically altered as determined by immunofluorescence. A pro‐inflammatory transcriptional profile, together with local posttranslational changes at the cell‐cell junctions, could explain the synergistic loss of barrier function observed with dual TNF signaling and endogenous SFK activation.Grant Funding Source: Supported by an AHA SDG grant 13SDG17100110 to APA.
Validation of a unilateral heating model to increase hindlimb length in growing mice (342.4)
Authors: Tamski Holly , Stanko Laura , Godby Justin , Efaw Morgan , Schlierf Thomas , Salisbury Travis , Ion Gabriella , Serrat Maria 
Published: June 2021

Limb length inequality is prevalent in nearly 90% of the population. Differences of 20mm can cause gait asymmetry and chronic back pain. Surgical treatments are invasive and alternatives are needed. Exposure to warm ambient temperature accelerates limb elongation in mice, suggesting that targeted heat could be a noninvasive way to promote limb length equalization. We tested the hypothesis that daily heat exposure on one side of the body will unilaterally increase limb length. Female mice (N=6) were treated with 40C unilateral heat for 40 minutes per day for 14 days post‐weaning. Controls (N=6) were not treated. Femur length was increased 1.3% on the heat‐treated side. Tibial elongation rate, measured by oxytetracycline labeling, was increased >12%. Body mass was unaffected. Histological analysis revealed morphological differences in the growth plate. To validate a protein assay for the next step, we developed western blotting methods to asses IGF‐I activation in whole proximal tibias. We show that IGF‐I (100ng/ml) stimulates Akt phosphorylation after 90 minutes in culture, suggesting that this method will be effective for measuring IGF‐I signaling in heat‐treated bones. This model will be important for elucidating mechanisms of heat‐enhanced growth. Our findings are relevant for the development of non‐invasive heat‐based therapies to increase length of specific bones without surgery.Grant Funding Source: Supported by NASA WV Space Grant Consortium and UK CCTS (NIH UL1TR000117)
Therapeutic delivery of placental stem cells to modulate vasculature and promote fracture repair (342.6)
Authors: Bahney Chelsea , Taylor Aaron , Sadat Ali , Tormos Kathryn , Miclau Ted , Maltepe Emin , Marcucio Ralph 
Published: June 2021

Blood supply to a bone fracture is a critical determinant of the rate and extent of healing. Therapies designed promote bone healing by stimulating angiogenesis have been proposed for a long time, yet, to date no effective treatments are available. In this work, we capitalize on a transient process that modifies the vasculature during pregnancy to support the developing fetus. Placental progenitors, trophoblast stem cells (TSCs), promote vasculogenesis in response to fetal hypoxia by physically remodeling the maternal arterioles and secreting angiogenic factors to generate a high volume, low pressure fluid exchange. We hypothesize that the therapeutic application of TSCs will promote vascular remodeling and enhance fracture healing. Our data shows that TSCs injected to non‐stabilized murine fractures engraft into the vasculature and enhance the local blood supply. Furthermore, injection of TSCs increased the volume of the cartilage callus 7‐days post fracture, leading to more bone after 14‐days of healing. To our knowledge, this is the first study evaluating the therapeutic potential of trophoblasts. Our results have the potential to enhance clinical outcomes in skeletal trauma, where there is often poor vascular perfusion. Importantly, this work may also have a significant impact on the broader field of regenerative medicine, since loss of organ function is often intimately tied to compromised vascularity.Grant Funding Source: NIH ‐ NRSA F32
Ultrasound imaging in anatomy: a supplement to dissection (343.3)
Authors: Lee Vaughan , Schneider Brandt 
Published: June 2021

Advances in ultrasound technology have made ultrasound imaging an important skill for physicians. To prepare our students for this clinical skill, TTUHSC/SOM is incorporating ultrasound in the undergraduate medical curriculum. Ultrasound imaging naturally integrates with anatomical dissections, providing a method to view anatomy in a clinical manner. Ultrasound sessions were designed for first year students and integrated with dissection sessions of the wrist, neck and liver. Wrist and neck sessions were conducted in a classroom with 15 ultrasound machines and 30 students in pairs scanning each other. The liver session was conducted in a simulation center with simulated patients and small groups of five students. The exercises were assessed with pre‐ and post‐test for each session. Average grades increased from pre‐ to post‐test; wrist (57.0/85.8), neck (75.8/92.8), and liver (71.4/95.4). Student opinions were assessed by survey on a five‐point Likert scale. Improved understanding of anatomy received scores of 3.43, 4.13 and 4.19, respectively, for the three sessions. Students indicated a desire for more in‐depth ultrasound sessions, including such statements as “LOVE the ultrasound sessions!” Supplementing anatomy sessions with ultrasound imaging enhanced dissections and introduced students to clinical skills.Grant Funding Source: Supported by the TTUHSC/SOM
A comparative examination of odontogenic markers in both toothed and toothless amniotes (344.3)
Authors: Lainoff Alexis , Moustakas Jacqueline , Kallonen Aki , Hämälainen Keijo , Smith Kathleen , Hu Diane , Marcucio Ralph , Hlusko Leslea 
Published: June 2021

It is a well‐known tenet of murine tooth development that BMP4 and FGF8 antagonistically initiate odontogenesis, but it is largely unexplored whether this tenet is conserved across amniotes. Additionally, changes in BMP4‐signaling have previously been implicated in evolutionary tooth loss in Aves. Here we demonstrate that Bmp4, Msx1, and Msx2 expression is limited proximally in the red‐eared slider turtle (Trachemys scripta) mandible, at stages equivalent to those at which tooth development is initiated in mice, similar to previously reported results in chicks. To address the question of whether the limited domains shared between the turtle and the chicken are indicative of an evolutionary molecular parallelism that resulted in the loss of the dentition, or whether the domains simply constitute an ancestral phenotype, we assessed expression of Bmp4, Msx1, Msx2, and Fgf8 expression in a toothed reptile (the American alligator, Alligator mississippiensis) and a toothed non‐placental mammal (the Gray short‐tailed opossum, Monodelphis domestica). We demonstrate that the Bmp4 domain is limited proximally in M. domestica and that the Fgf8 domain is limited distally in A. mississippiensis just preceding odontogenesis. Additionally, we show that Msx1 and Msx2 expression patterns in these species differ from those found in mice. Our data suggest that a limited Bmp4 domain does not necessarily correlate with edentulism, and reveal that the initiation of odontogenesis in non‐murine amniotes may be more complex than previously imagined. Our data also suggest a partially conserved odontogenic program in T. scripta, as indicated by the conserved mandibular expression domains of Pitx2, Pax9, and Barx1 and by the presence of Shh‐expressing palatal epithelium in some Yntema stage 17 (Y17) T. scripta specimens, which we hypothesize may represent potential dental rudiments based on the fossil record of Testudinata.Grant Funding Source: Supported by NIH‐NIDCR‐R01DE018234 and NSF‐BSC‐0616308 with REU supplement.
Activation of musculoskeletal development and repair mechanisms in the regenerating lizard tail (344.7)
Authors: Hutchins Elizabeth , Tokuyama Minami , Eckalbar Walter , Fisher Rebecca , Rawls Alan , Wilson‐Rawls Jeanne , Kusumi Kenro 
Published: June 2021

Uniquely among amniote vertebrates, lizards can lose their tails and regrow a functional replacement. These regenerated tails, which have an organization distinct from the original tail, contain newly formed hyaline cartilage, muscle, vasculature, spinal cord, and skin. Using Illumina RNA‐Seq technology, we have identified over 300 differentially expressed (DE) genes along the proximal/distal axis of the regenerating tail at a mid‐growth stage (n=5). Histological and immunohistological analysis reflect these transcriptomic data. Specifically, there are proliferative cells throughout the proximal/distal axis and proliferative markers are expressed throughout the proximal/distal axis. However, cells progressively show differentiation towards the proximal region of the regenerating tail, and genes with high expression in this region include myogenic regulators and factors for muscle structure and differentiation. In contrast, genes with high expression in the regenerating tail tip include factors for wound and inflammatory response, hormonal and homeostatic regulation, and skeletal system development, including regulation of the Wnt pathway. Thus, these studies have identified components of a genetic program for regeneration in the lizard that includes both developmental and adult repair mechanisms, indicating value in the translation of these findings to future regenerative therapies.Grant Funding Source: Supported by NIH NCRR/ORIP Grant R21RR031305 and Arizona Biomedical Research Commission
Child dietary intake data by tablet‐based 24‐hour recall in rural Zambia (36.3)
Authors: Lewis Bess , Siamusantu Ward , Dyer Brian , Talegawkar Sameera , Klemm Rolf , Schulze Kerry , Palmer Amanda , West Keith 
Published: June 2021

Digital data collection represents the leading edge for dietary assessment in rural areas of low‐income countries, providing ease of use, speed of training and rapid availability of food and nutrient data. A multi‐pass 24 hour dietary recall program for the tablet‐based Android operating system was developed and used to collect dietary intake data for 4 to 8 year old children in rural Zambia. A list of 608 food items was incorporated into the tablet programming. Mothers of children enrolled into a biofortified maize flour efficacy trial were interviewed about the foods their child consumed over the previous 24 hours (n=1226). Staff followed prompts on the tablet for administering questions and entering data on the type, cooking method, quantity and source of food consumed at six time periods over the course of the previous 24 hours. At baseline, 8379 food items of 243 different types were reported. Children’s diets were predominated by maize porridge and vegetables such as leafy greens, tomato and onion. Dietary data uploaded from the tablets was linked to extant regional and USDA food composition tables using SAS 9.3 programming. The tablet was an effective tool for characterizing diets in a rural, low income country setting.Grant Funding Source: Supported by HarvestPlus