bluuebunny/crossref_metadata_2025_split huggingface dataset:
Red Raspberries and Insulin Action: Understanding the Role of Red Raspberry Consumption on Postprandial Metabolic Indices
Authors: Xiao Di , Huang Yancui , Park Eunyoung , Edirisinghe Indika , Burton‐Freeman Britt 
Published: November 2023

Red raspberries contain appreciable amounts of polyphenols and dietary fiber with documented biological activities suggesting metabolic benefits for people at risk for diabetes mellitus (DM). This study aimed to investigate the acute effect of red raspberries on meal‐induced postprandial metabolic responses in individuals with impaired fasting glucose and hyperinsulinemia (PreDM) or normo‐glycemia and insulinemia (Reference). Twenty eight adults (PreDM, n=17, age 36±13 y, Body Mass Index (BMI) 30.3±5.1 kg/m2, fasting blood sugar 110.7±0.9 mg/dL, fasting insulin 13.2±1.4 uIU/mL and Reference, n=11, age 28±6 y, BMI 23.1±3.0 kg/m2, fasting blood sugar 93.5±1 mg/dL, fasting insulin 3.7±0.4 uIU/mL) were randomized in a 2:1 ratio, respectively to a 3‐arm, single blinded, crossover clinical trial. Participants were provided 0 (Control), 125, or 250 g frozen red raspberries with a high fat high carbohydrate breakfast meal on 3 separate occasions. Blood samples were collected over 24 h. Preliminary analyses indicate a significant reduction in postprandial glucose when 250 g red raspberries (~2 cups) were consumed with the meal compared to the 125 g red raspberries or control study arms (p<0.05). A significant study group*time*treatment interaction (p<0.0001) indicated that the glucose lowering benefits of the 250 g red raspberry meal was more pronounced in the PreDM group than the Reference group. Additionally, postprandial insulin was significantly lower when either dose of red raspberries vs Control (no raspberries) were consumed with the meal (all subjects, p<0.05). No treatment related effect of red raspberries was observed on postprandial triglyceride concentrations (p=0.08), although the triglyceride response was significantly greater in the PreDM than Reference group (p<0.05). These data suggest that red raspberries have a role in post meal glycemic control in individuals with PreDM; and furthermore, indicate the effects may be related to an action of improved insulin sensitivity in both PreDM and Reference group individuals.Support or Funding InformationThis research is funded by National Processed Raspberry Council.
Quantification of Triterpenoid Acids in North Carolina Heritage Apple Peels
Authors: Root Martin , Petroski Weston , Lambiase Samantha , Wilson Brooke , Serini Justin 
Published: November 2023

BackgroundPentacyclic triterpenoid acids are found in a variety of medicinal plants and common foods. In particular, oleanolic acid, ursolic acid, and betulinic acid, found in the cuticular wax on apple peels, have anti‐inflammatory, anti‐diabetic, and cancer‐inhibiting properties in murine and in vitro models. This project aimed to find the variation of these three acids in western North Carolina heritage and commercially grown apples from the 2014 season.MethodsA total of 48 North Carolina apple cultivars were studied. Apples peels were collected and stored in −80° C. For extraction and analysis, peel samples were freeze dried, ground, and soaked in ethanol overnight. Samples were then extracted twice with ethanol. The filtrate was dried and resuspended in methanol for reverse‐phase isocratic HPLC analysis. Separation was achieved in 20 minutes with a methanol/water/acetic acid mobile phase (85/15/0.1), monitored at 207 nm.ResultsAll three triterpenoids were quantifiable in the 48 cultivars analyzed. Average total triterpenoid content was 19 mg/g dry peel weight, ranging from 2.0 mg/g (Roxbury Russet) to 36.3 mg/g (Virginia Gold). Betulinic, oleanolic, and ursolic acid averaged 0.26, 3.6, and 14.9 mg/g, respectively. Russet cultivars, such as Roxbury Russet and Sour Rusty Coat tended to contain less total triterpenoids than waxy cultivars such as Virginia Gold and Sweet Sixteen. No substantial differences were observed between green/yellow cultivars and red ones or across the season from early to late cultivars.ConclusionHeritage apple peels are a variable source of potentially salutary pentacyclic triterpenoids. Total amounts may vary almost 20 fold across cultivars with ursolic acid predominating.Support or Funding InformationAppalachian State University Office of Student Research
Dietary effect of Kaempferia parviflora, a PPARγ agonist, on glucose tolerance in non‐obese type diabetic mice
Authors: Ochiai Masaru , Azuma Yoshiyuki , Matsuo Tatsuhiro 
Published: November 2023

Type 2 diabetes mellitus (T2DM) in Asian countries is often characterized as non‐obese type. PPARγ agonists are known to reduce adipocyte size and improve adiponectin secretion and insulin resistance, but to induce abdominal fat accumulation as an adverse effect. Search for PPARγ agonists which have little adverse effects from natural food resources is desirable for people with non‐obese T2DM. We previously showed that Kaempferia parviflora (black ginger, BG) and its ethanol extract (BGE) had PPARγ agonistic activities in a binding study, and exerted a beneficial impact on adiponectin secretion in an animal study. Although some studies showed anti‐T2DM effects of BG in diet‐induced obesity animal model, little is known to have suppressive effect of BG and BGE on T2DM in non‐obese T2DM model. We here investigated the effect of BG and BGE in diet on glucose tolerance in NSY mice with non‐obese T2DM. Male NSY mice were divided into five dietary groups and fed each diet for 8 weeks; mice fed an AIN‐93G diet (N‐LF), high‐fat and high‐sucrose diet (HF), HF diet supplemented with BG (1%) (BG), and HF diet supplemented with BGE (0.19%) (BGE). Half of mice in HF group were treated with pioglitazone (3 mg/kg) as PPARγ agonistic positive control (PIO). ICR mice fed the LF diet are used as non‐diabetic control (I‐LF). At the end of 6th and 7th week, oral glucose and insulin tolerance tests (OGTT and ITT) were respectively carried out. In OGTT, elevation of plasma glucose level was significantly suppressed in the BG and BGE groups. In ITT, plasma glucose level was significantly lowered in the BG and BGE groups. These effects were equivalent to those of pioglitazone. In conclusion, BG and its methanol extract can be effective for prevention of insulin resistance and T2DM.Support or Funding InformationThis work was supported by JSPS KAKENHI Grant Number 16K21349 and Mishima Kaiun Memorial Fundation.
A Closer Look at the Influence of Processing on Polyphenol Composition and Degree of Polymerization in Wine and Wine‐like Products
Authors: Griffin Laura Elizabeth , Neilson Andrew , Stewart Amanda 
Published: November 2023

Associations of moderate wine intake with positive health outcomes are often hypothesized to be attributable to polyphenols in wine. Polyphenol size, or mean degree of polymerization (mDP) may influence bioactivity. This study examined how starting materials and processing parameters in the wine production process impact the polyphenolic profile in finished wine and wine‐like products. Cabernet Sauvignon grapes were fermented under typical red winemaking conditions and following an extended chilled fruit maceration period. Additionally, rosé wine was made from the same grapes processed and fermented under typical rosé winemaking conditions, with excess skins, with excess seeds, and with excess crushed seeds (from the same lot of grapes). Analytical replicates (n =5) of each wine or wine‐like product (n = 8) were thiolyzed to determine mean degrees of polymerization (mDP) using UPLC‐MS, and the polyphenolic profile of each wine was characterized using normal‐phase HPLC. Examination of the normal‐phase HPCL chromatograms revealed that the polyphenol profiles of the wines were different, but most peaks were identified in the monomer region. Interestingly, the rosé wines with excess seeds had the greatest amount of oligomer (DP = 2–8) and polymer (DP >9–10) compounds. Monomers were the most abundant flavanols present in all wines. Due to the high concentrations of baseline monomers, mDP of flavanols were not significantly different among the products (p > 0.05). mDP for each wine was approximately 2, indicating that the average size of the flavanols in these products were dimers, not large polymers. It can be concluded that processing parameters, even when pushing the boundaries of winemaking practice, are not the primary factor enriching wine in large polymeric flavanols. Flavanol solubility may limit enrichment potential in wine, particularly for larger species. Future research in this area will include products made from other fruits, and subjected to other processing methods such as oxidation and cooking.Support or Funding InformationVirginia Agricultural Experiment Station, Virginia Tech Translational Obesity Interdisciplinary Graduate Education Program
Paradoxical effects of PGC‐1 isoforms on retinal pigment epithelium: Implication for neovascular retinal diseases
Authors: SAINT‐GENIEZ MAGALI , Charles Quincy , Rosales Mariana , Khadka Arogya , Iacovelli Jared 
Published: November 2023

Age‐related macular degeneration (AMD) is the leading cause of blindness in the elderly population of industrialized countries. A compelling set of evidences indicates that oxidative damage and mitochondrial dysfunctions of the retinal pigment epithelium (RPE) are key early events in age‐related macular degeneration (AMD) but the root mechanisms for RPE pro‐angiogenic switch remain unclear. The transcriptional co‐activators, peroxisome proliferator‐activated receptor‐gamma coactivator‐1alpha and beta (PGC‐1α and β) are critical regulators of mitochondrial biogenesis and oxidative metabolism in many tissues. We recently demonstrated that RPE maturation in vitro is correlated with PGC‐1α induction, mitochondrial biogenesis and increased oxidative phosphorylation. Furthermore, we showed that PGC‐1α controls RPE cells oxidative metabolism and efficiently protects cells from cytotoxic oxidative damage. Remarkably, our results indicate that, conversely to PGC‐1α, PGC‐1β expression is repressed during RPE maturation in a PGC‐1α‐dependent manner. Here we examined the role of PGC‐1β in RPE biology and response to oxidative damage. We showed that while forced expression of PGC‐1β stimulates RPE mitochondrial respiration similarly to PGC‐1α, PGC‐1β significantly repressed the expression of critical antioxidant transcription factors (FOXO3 and NFE2L2) and enzymes (HMOX1, CAT) leading to increased oxidative damage and cell death in RPE exposed to cytotoxic levels of H2O2 (0.5 mM for 18 hours). We next evaluated whether AMD‐related toxicants could induce PGC‐1β expression in cultured RPE and demonstrated that PGC‐1β, but not PGC‐1α, is selectively induced by cytotoxic doses of oxidized LDL (500 μg/ml for 24 hrs) while non‐oxidized LDL had no effect. Finally we demonstrated that PGC‐1β overexpression in RPE robustly induced PlGF (Placenta Growth factor) expression but not VEGFA and strongly repressed the RPE‐secreted anti‐angiogenic factors, thrombospondin‐1 (THBS1) and PEDF. All together, these findings indicate that PGC‐1s exert paradoxical functions in RPE and that pathologic induction of PGC‐1β may promote RPE oxidative damage and choroidal neovascularization.Support or Funding InformationSupported by the National Institutes of Health (1R01EY023682 to M.S.G.), a Research to Prevent Blindness Unrestricted Grant (M.S.G), donations to the Macular Degeneration Research, a program of the BrightFocus Foundation (M.S.G) and the NIH National Eye Institute core grant P30EY003790.
Expression of Glucose Transporter Proteins (GLUTs) in Human Placental Tissue after Normal vs. Diabetic Pregnancy
Authors: Szukiewicz Dariusz , Stanirowski Pawel Jan , Pyzlak Michal , Abdalla Nabil , Sawicki Wlodzimierz , Cendrowski Krzysztof 
Published: November 2023

Altered expression of GLUTs in diabetic placenta has been suggested recently by independent authors, including the role of insulin therapy as a possible modulatory factor. In this study we examined comparatively the expression of GLUTs (GLUT‐1, GLUT‐4, and GLUT‐9) in the placental tissue obtained after normal healthy and diabetic pregnancies. Additionally, the effect of insulin therapy on the expression of selected GLUTs isoforms was analyzed. Placental samples derived from healthy gravidas after normal term pregnancies (N = 25) and obtained after diabetic pregnancies, including diet‐controlled gestational diabetes mellitus (GDMG1; N = 16), insulin‐controlled GDM (GDMG2; N = 6), and pre‐gestational DM (PGDM; N = 6). To visualize GLUT‐1, GLUT‐4, and GLUT‐9, standard immunohistochemical procedures were used with the respective anti‐GLUT antibodies. Thereafter, computer‐assisted quantitative morphometry was performed to identify immunostained GLUTs in 5‐μm paraffin‐embedded sections of the placental specimens, and the final results were adjusted for the mean microvascular density with the permitted margin of error not exceeding ± 5 %. Morphometric evaluation revealed a significant increase (p < 0.05) in the mean expression of GLUT‐4 and GLUT‐9 in insulin‐dependent diabetes (GDMG2 + PGDM) as compared to both, the control and GDMG1 groups. A significant increase in the mean GLUT‐1 expression was observed only in placental specimens obtained from PGDM group (p < 0.05). The differences in GLUTs expression between GDMG1 group and the healthy controls did not reach statistical significance. In conclusion, our results have confirmed the presence of GLUT‐1, GLUT‐4 and GLUT‐9 proteins in the trophoblast from both, uncomplicated and diabetic pregnancies. Interestingly, insulin therapy may significantly increase placental expression of GLUT‐4 and GLUT‐9 isoforms, and partially GLUT‐1, in diabetic gravidas classified as GDMG2 and PGDM.Support or Funding InformationWUM grant: 2WA/PM23D/14
ErbB Receptors Signaling Promote Endothelial Phenotype of Human Left Ventricular Epicardial Highly Proliferative Cells
Authors: Ryzhov Sergey , Robich Michael P. , Rath Rutwik , Roberts Daniel J , Quinn Reed , Kramer Robert S , Sawyer Douglas B 
Published: November 2023

Despite a long history of heart‐specific ErbB signaling research, the role of ErbB receptors in cardiac non‐myocyte cells is largely unknown. We recently have shown that neuregulin‐1b (NRG‐1b) prevented transition of CD105posCD31neg cells obtained from mouse heart into myfibroblasts. These cells can form single‐cell derived colonies with high proliferative potential and capability to differentiate into different cell types. The present study examines the expression of ErbB receptors on highly proliferative cells (HiPC) obtained from human LV epicardium and the role of ErbB receptor subtypes in the regulation of CD31, VEGFR2 and Tie2 endothelial markers expression. Left ventricular free wall epicardial biopsies from human subjects undergoing open heart surgery were used to obtain myocytes‐depleted cardiac cell suspension. These cells were seeded at low cell density to produce colonies of HiPC. We found that human HiPC are characterized by expression of all four ErbB receptors. The level of ErbB receptors varied among HiPC obtained from different subjects. ErbB2 and ErbB3 showed highest level of inter‐individual variability compared to ErbB1 and ErbB4. Flow cytometric analysis revealed strong expression of CD105 (endoglin), CD73 (ecto‐5′‐nucleotidase) and CD29 (integrin β1), and lack of CD34, CD117 (c‐kit), CD11b, and CD45 on HiPC. In addition, we detected expression of CD49f (integrin alpha 6), CD90 (Thy‐1) and CD31 (PECAM‐1) on cell surface of HiPC. A strong positive correlation was found between CD31/PECAM‐1 and ErbB2 but not ErbB1, 3 or 4. To determine the role of ErbB receptors, we incubated HiPC in the absence or presence of EGF to stimulate ErbB1, and NRG‐1b to stimulate ErbB3 and ErbB4 receptor activation. We found that both EGF and NRG‐1b ligands promoted CD31 cell surface expression on HiPC which express high level of ErbB2 (ErbB2hi). In contrast, no effects of ErbB ligands were seen in ErbB2low/− HiPC. Only EGF but not NRG‐1b increased VEGFR2 expression on HiPC. No difference was found between ErbB2hi and ErbB2low/− HiPC, indicating that ErbB1 receptors are solely responsible for the upregulation of cell surface expression of VEGFR2. In addition, both EGF and NRG‐1b induced up‐regulation of Tie2 on HiPC to a similar degree, irrespective of the level of ErbB2 expression. Thus our data identified a novel role of ErbB signaling in promotion of endothelial phenotype of human HiPC.Support or Funding InformationSupported in part by Acorda therapeutics, Inc, U01 HL100398, and the Osher Cardiovascular Research Fund at Maine Medical Center
Naturally Occurring Mechanisms for the Resolution of Pulmonary Vascular and Right Ventricular Remodeling
Authors: Shults Nataliia V. , Suzuki Yuichiro 
Published: November 2023

Pulmonary arterial hypertension (PAH) is a lethal disease and improved therapeutic strategies are needed. Increased pulmonary arterial pressure, due to vasoconstriction and vascular remodeling, causes right ventricle (RV) failure and death. The treatment of Sprague‐Dawley rats with the SU5416 injection and the exposure to chronic hypoxia for 3 weeks followed by maintenance in normoxia promotes progressive and severe PAH with pathologic features that resemble human PAH. At 5–17 weeks after the SU5416 injection, PAH is developed with pulmonary vascular remodeling as well as RV hypertrophy and fibrosis. The present study investigated subsequent events that occur in these PAH animals. At 35 weeks after the SU5416 injection, rats still maintained high RV pressure, but pulmonary vascular remodeling was significantly reduced. Metabolomics analysis revealed that lungs of normal rats and rats from the 35‐week time point had different molecular profiles. Despite the maintenance of high RV pressure, the fibrosis was resolved at 35‐weeks. Masson's trichrome stain and Western blotting monitoring collagen 1 determined 12% fibrosis in the RV at 17‐weeks, and this was decreased to 5% at 35‐weeks. The expression of a‐smooth muscle actin (a marker of myofibroblasts) was elevated at 17‐weeks compared to control, and this was normalized at 35‐weeks.ConclusionsThese results suggest that biological systems possess natural ways to resolve pulmonary and RV remodeling. The resolution of RV fibrosis appears to involve the reduction of myofibroblast‐dependent collagen synthesis. Understanding these endogenous mechanisms should help improve therapeutic strategies to treat PAH and RV failure.Support or Funding InformationNIH
TNFalpha and IL‐1beta Synergically Decrease VEGFR2 and Increase VEGFR1 Protein Expression in Endothelial Cells
Authors: Yan Xiaocai , Managlia Elizabeth , De Plaen Isabelle G 
Published: November 2023

Necrotizing enterocolitis (NEC) is the most serious gastrointestinal disease affecting premature infants. Among other inflammatory cytokines, TNFalpha and IL1beta are significantly increased in intestinal tissues during NEC induction in a neonatal mouse model. We previously found that intestinal villous endothelial cell (EC) proliferation and VEGFR2 expression are decreased, and mucosal vascular network development impaired during experimental NEC induction. Furthermore, inhibiting VEGFR2 kinase activity increased NEC severity. However, whether cytokines directly affect VEGFR2 expression in neonatal intestinal EC remains unknown. Here, we hypothesize that increased inflammatory cytokines may affect microvascular development by decreasing intestinal EC VEGFR2 signaling. To test our hypothesis, EC isolated from mouse neonatal intestine tissue and HUVEC were cultured in vitro and incubated with TNFalpha and/or IL1beta and VEGFR1 and 2 assessed by western blot. We found that: 1) TNFalpha treatment of both mouse EC and HUVEC for 12 hours dramatically decreased their VEGFR2 expression while inducing an increase in VEGFR1 expression. 2) IL‐1beta treatment for 12 hours decreased VEGFR2 expression without affecting VEGFR1 in both mouse EC and HUVEC. 3) When EC (both neonatal mouse intestinal EC and HUVEC) were incubated with IL1beta and TNFalpha together, there was a synergistic decrease in VEGFR2 expression and a synergistic increase in VEGFR1 protein expression. Other inflammatory cytokines found to be increased in NEC, such as IL6, IL10, CCL2 and CCL20 had no effect on HUVEC VEGFR1 and 2 expression. This suggests that TNFalpha and IL1beta produced during NEC induction may promote disease progression by impairing the development of the mucosal intestinal microvasculature, thus further affecting intestinal tissue perfusion.Support or Funding InformationNIH grant RO1HD060876 and Ann & Robert H. Lurie Children's Hospital of Chicago Foundation
Inhibition of the Receptor for Advanced Glycation End‐products (RAGE) protects from secondhand smoke (SHS) induced intrauterine growth restriction (IUGR) in mice
Authors: Lewis Joshua B , Mejia Camilo A , Jordan Clinton , Monson Troy D , Bodine Jared S , Dunaway Todd M , Egbert Kaleb M , Wright Tanner J , Ogden K Connor , Broberg Dallin S , Hall Parker D , Nelson Shawn M , Hirschi Kelsey M , Reynolds Paul R , Arroyo Juan A 
Published: November 2023

Intrauterine growth restriction (IUGR) is a disease affecting 10% of all pregnancies. IUGR is associated with maternal, fetal, or placental abnormalities, but studies investigating the effects of secondhand smoke (SHS) exposure and IUGR are limited. Receptors for Advanced Glycation End‐products (RAGE) are pro‐inflammatory transmembrane receptors increased by SHS in the placenta. We tested the hypothesis that inhibition of RAGE during SHS exposure protects from smoke‐induced IUGR. C57Bl6 mice were exposed to SHS or SHS + semi‐synthetic glycosaminoglycan ethers (SAGEs) known to inhibit RAGE signaling. RAGE −/− mice were also exposed to SHS. Trophoblast cells were treated with cigarette smoke extract (CSE) with or without SAGEs in order to address the effects of RAGE inhibition during trophoblast invasion in vitro. SHS treated mice demonstrated a significant reduction in fetal weight (7.35‐fold; p≤0.0001) and placental weight (1.13‐fold; p≤0.0001) compared with controls. RAGE −/− mice were completely protected from fetal and placental weight deviations when exposed to SHS. Mice co‐treated with SHS and SAGEs were protected from SHS‐induced fetal weights decreases (4.22‐fold; p≤0.0001). SHS treatment of C57Bl6 mice activated placental ERK (2.61‐fold, p≤0.05), JNK (1.79‐fold, p≤0.05), and p38 (2.44‐fold, p≤0.05) and the expression of inflammatory mediators including TNF‐α (1.34‐fold p≤0.05) and IL‐1β (1.03‐fold p≤0.05). SHS‐mediated activation of these molecules was reduced to basal levels when SAGE was co‐administered. Invasion of trophoblast cells decreased 92% (p<0.002) when treated with CSE and CSE‐mediated invasion was completely reversed by SAGEs. We conclude that inhibition of RAGE protects against fetal weight loss during SHS‐induced IUGR. Our results further suggest that there is a direct correlation between RAGE activation and the development of IUGR during SHS. These studies provide insight into tobacco‐mediated IUGR development and clarify avenues that may be helpful in the alleviation of placental complications.Support or Funding InformationThis work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR) and a BYU Mentoring Environment Grant (PRR).