bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric Oxide‐Mediated Nanomolar Vasodilator Potencies of Glycosylated Anthocyanins do not Correlate with Redox Potential
Authors: Garcia‐Huidobro J Pablo , Calfio Camila , Donoso M Veronica , Donoso Francisca , Silva Camila 
Published: June 2021

Calafate is an endemic Patagonian shrub (Berberis Microphylia); its berries are rich in polyphenols, including 3‐glycosylated anthocyanins (GA, delphinidin, petunidin or malvidin) or mono or disaccharide conjugated quercetin (Q). The chemical profile of Calafate berries is well characterized and indicates its high redox potential; pharmacological properties are virtually unknown. From ethno‐pharmaceutical reports we hypothesized that Calafate polyphenols are vasodilators and ascertained whether this effect is related to their cell antioxidant activity (CAA).Vascular responses of GA and Q were assessed perfusing the intact rat arterial mesenteric bed or following endothelium denudation. The role of NO was assessed in mesenteries perfused with an eNOS inhibitor (L‐NNA). Luminally accessible NO was determined by chemiluminescence; intracellular NO was quantified by DAF fluorescence in isolated mesentery endothelial cells. Antioxidant capacity was quantified either by 1,1‐Diphenyl‐2‐picryl‐hydrazyl antioxidant assay (DPPH) or by CAA assessment. Extracellular ATP was assessed by chloroacetaldehyde derivatization to yield fluorescent purines; the nucleotide is related to NO production in endothelial cells.GA proved potent vasodilators with EC50s of 84.1 ± 0.3, 65.8 ± 0.4 and 17.7 ± 0.1 nM, respectively; aglycones exhibited similar EC50s. The maximal effect of GA did not exceed 56 ± 3.7% efficacy compared to acetylcholine (EC50 was 43.4 ± 0.1 nM with 100% efficacy) while the Q EC50 was 12.8 ± 0.1 μM, with 99 ± 4.1%. The GA‐induced vasodilatation was totally endothelium‐dependent; while the Q response showed partial endothelium‐dependence. The degree of GA vasodilatation correlated with luminal NO (r2 = 0.83), confirming NO as the final intracellular signal. 30 μM Q increased both extracellular ATP secretion from endothelial cells plus intracellular DAF‐fluorescence (P<0.05), an indication that part of the Q response involves NO as the final effector. While Q exhibited the highest antioxidant effect in both the DPPH or CAA (p<0.01), the GA showed a 60‐fold lower potential than Q in the CAA test, indicating that the CAA is not related to its vasodilator profile, which apparently relies on eNOS allosteric modulation.In sum, GA are novel and potent endothelium‐dependent vasodilators, linked to modulation of NO production.Support or Funding InformationFunded by FONDECYT 117‐0842 and 21141226 to CC and CEDENNA FB0807This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deletion of T1R3 reduces atherosclerosis and liver triglyceride accumulation in ApoE−/− mice fed a high‐fat diet
Authors: Shojaat Shayla , Engman Samuel , Hofferber Jason , Keomanivong Faithe , Wauson Eric M 
Published: June 2021

To maintain homeostasis, cells continuously evaluate and adjust to their nutrient availability and current energy state. A cell's response to the fed state requires the presence of amino acids and other nutrients, which signal to the mammalian target of rapamycin complex 1 (mTORC1) coordinating cell growth, protein translation, and autophagy. The umami taste receptor, which is a heterodimer between the G protein‐coupled receptors T1R1 and T1R3, is a direct sensor of amino acid availability and signals to mTORC1. Reducing the expression of T1R1/T1R3 in mice and pancreatic beta and cardiomyocyte cell lines diminishes the activation of mTORC1 by amino acids, thereby inducing autophagy. Previous research suggests that elevated autophagic flux reduces the development and progression of atherosclerosis by protecting cells from oxidative stress, reducing apoptosis within atherosclerotic lesions, and promoting lesion stabilization by degrading intracellular components that are harmful to the cell. Other studies suggest that increased autophagic flux decreases the progression of Non‐Alcoholic Fatty Liver Disease (NAFLD) by reducing hepatocyte lipid accumulation and liver inflammation. We hypothesized that the deletion of T1R3 in ApoE−/− mice would decrease aortic atherosclerotic plaque buildup and decrease hepatosteatosis by increasing autophagic flux. Our data suggest that T1R3−/− ApoE−/− mice have less liver lipid accumulation and reduced atherosclerotic plaque area when compared to T1R3+/+ApoE−/− mice. Taken together, these data suggest that modulation of nutrient and amino acid‐sensing GPCRs like T1R1/T1R3 could be used as a potential therapeutic strategy for cardiovascular disease.Support or Funding InformationAmerican Heart Association (15SDG25090279) and Iowa Osteopathic Education and Research Funds (E.M.W.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anti‐adipogenic Activity of Terminalia pallida
Authors: BADRI KAMESWARA RAO 
Published: June 2021

Obesity rates are rising globally, with 1.5 billion overweight and 500 million obese worldwide. According to The Centers for Disease Control and Prevention, almost 2/3rds of the United States population is either overweight or obese. Growing obesity rates in children and adolescents makes the obesity pandemic more alarming and solutions more critical. Further, non‐Hispanic Black and Hispanic Americans are more prone to this disease/condition, making it also a health disparity. Obesity increases the risk for insulin resistance, diabetes mellitus, dyslipidemia, hypertension, sleep apnea, cardiovascular disease and certain types of cancer (4). Only limited obesity management options are available, including behavioral interventions, lifestyle modification and invasive surgeries.New drug development remain the cornerstone of anti‐obesity research due to the limited availability of drug treatments. Further, due to reduced costs, fewer side effects and cultural significance, many are opting for complementary treatments. Terminalia pallida (TP) is one such plant that is been used ethno‐botanically to treat metabolic diseases. Hence, here we investigated the anti‐adipogenic activity of TP. We used 3T3‐L1 embryonic fibroblast‐preadipocyte cells treated with or without adipogenic cocktail (1 μM dexamethasone, 10 μg/mL insulin and 0.5 mM 3‐isobutyl 1 methylxanthine) to induce adipogenesity. We treated the 3T3‐L1 cells with various concentrations of ethanolic extract of Terminalia pallida fruit (TP‐50, 25 and 10 μg/ml) or Simvastatin (1 μM), a known anti‐lipidemic drug. Ten days post‐adipogenic induction, the adipogenic cocktail‐treated 3T3‐L1 preadipocytes differentiated into adipocytes. However, TP‐treated groups showed significant inhibition of adipocyte formation. The Simvastatin‐treated group also showed anti‐adipogenic activity, as evidenced by the reduced size and number of adipocytes. Expression of the key adipogenic markers PPARγ2 and C/EBPα was decreased in the TP‐treated group compared to untreated control. We further investigated the cellular mechanisms by which TP elicit the antiadipogenic function. Our studies conclude that TP significantly decreased proliferation and elevated apoptosis in 3T3‐L1 adipocytes, indicating that partially TP shows its anti‐adipogenic function by regulating preadipocyte and adipocyte cell cycle.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Persistence of Exercise Training Effect on Amyloid Pathology
Authors: Lawson Justin E , Dobbs Kaylin C. , Jensen Jordan L. , Phelps Eva A. , Timson Benjamin F. , Zimmerman Scott D. 
Published: June 2021

BackgroundEarly life aerobic exercise training (ET) reduces amyloid beta (Aβ) plaque load and improves cognition in transgenic mouse models of Alzheimer's Disease (Yuede, et al. Neurobiology of Disease, 35, 2009). Many people are physically active into early adulthood, but it is less likely that they continue lifelong ET. In addition, it is unclear if the benefits of early ET persist into later life. We examined the persistence of ET effects by measuring cognition and plaque load at 12 months of age in transgenic mice that had participated in ET during various periods of life.MethodsThree groups of male APP/PS1 mice ran on a motorized treadmill at 20 m/min five days a week for 12 weeks at different times during their first year of life; EARLY (from 3–6 months), MIDLIFE (from 6–9 months), and LATE (from 9–12 months of age). A fourth group did not exercise train and served as sedentary controls (SED). At 12 months of age, all groups underwent Novel Object Recognition (NOR) and Morris Water Maze (MWM) testing to assess recognition memory and spatial learning. Brain hemispheres were collected for Thioflavin S staining to assay plaque load and for protein quantification. Soleus muscles were assayed for citrate synthase activity to verify the effectiveness of the ET regimen.ResultsOne‐way ANOVA revealed a significant main effect of ET on citrate synthase activity with the LATE group having 25.8% greater activity. There was also a significant effect of ET on cognition though the effect was limited to the most recently trained groups and absent in the EARLY animals. There was a main effect of ET group on the latency to platform during the MWM Place Trials with significantly lower latencies in the MIDLIFE and LATE groups compared to SED and EARLY. Similarly, there was an increased time in target region in the LATE group compared to others in the MWM Probe trials. Recognition memory was also improved in the LATE group as demonstrated by a greater novel investigation time relative to the other groups. Finally, there was significantly lower plaque load in MIDLIFE and LATE animals (59.6% and 45.8% lower than SED, respectively).ConclusionThere are significant cognitive benefit of ET, but little persistence once ET is discontinued in APP/PS1 mice. Interestingly, LATE group data provide evidence that beginning ET later in the amyloidogenic process is still effective at preserving cognitive function and reducing plaque load. Protein analysis is on‐going and will assess the impact of ET on brain signaling and clearance proteins in these 4 groups.Support or Funding InformationSupported by Missouri State Research FundsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acute Phase Response to Exertional Heat Stroke in Mice
Authors: Iwaniec John D , Robinson Gerard D , Garcia Christian D , Murray Kevin D , Laitano Orlando D , Clanton Thomas D 
Published: June 2021

Exertional heat stroke (EHS) is a serious illness and a common occurrence for military personnel, athletes, and occupational workers. Innate immunity is vital for cell survival and tissue repair needed for recovery following EHS. Previously, our group revealed a unique cytokine response to EHS where circulating interleukin‐6 (IL‐6) peaked at 0.5 h post EHS; however, little is known about the acute phase response, a subsequent response to IL‐6 signaling. Therefore, we hypothesized that EHS would induce an acute phase response that would be observed in skeletal muscles, hepatocytes, and in the circulation.PurposeTo determine if acute phase proteins (APPs), fibrinogen, lipocalin, and serum amyloid A1 (SAA1) are expressed in liver and skeletal muscle following EHS and whether these result in their accumulation in the circulation.MethodsMice were subject to a standardized EHS protocol using a forced running wheel. While running, the mice experienced environmental temps of 37.5 (EHS) or 22.5 (exercise control) until they experienced loss of consciousness (at a core temperature of ~42.2). The tibialis anterior, soleus, liver, and plasma were collected from the mice (n = 8/group) at 0.5, 3, 24, 96, 216, or 336 h post‐EHS. Tissue samples from exercise controls were retrieved at 3 and 96 h post exercise.ResultsUsing protein immunoblots, a significant increase of SAA1 was observed in liver at 3 h of recovery and peaked at 24 h when compared to the exercise control (2.4 ± 1.2*, 2.5 ± 1.4* vs. 0.1 ± 0.1 AU/total protein; respectively). Moreover, circulating SAA1 was observed at the 3 h time point (5.0 ± 3.8 AU/TP). No difference for SAA1 was observed for any other time points when compared to the control. In the liver, fibrinogen, and lipocalin were undetectable for any of the recovery timepoints. No acute phase proteins were detected in skeletal muscle; although, preliminary data revealed that SAA1 expression is elevated in skeletal muscle during sepsis.ConclusionA single episode of EHS alters the expression of SAA1 in mouse liver and plasma. This observation is consistent with an acute phase response to thermal damage, in response to IL‐6 signaling, initiating cell survival and tissue repair pathways needed for recovery.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Perception of Weight Status and BMI Based on Self‐Reported Weight and Height Among Undergraduate Students
Authors: Khanna Deepesh 
Published: June 2021

IntroductionUniversity students, especially women perceive themselves as overweight. This is of major concern because inappropriate weight perceptions can lead to inappropriate dietary behaviors or a sedentary lifestyle. Perception of overweight at the normal or underweight range of BMI leads to conditions like anorexia nervosa or bulimia.MethodsThe cross‐sectional study was conducted among undergraduate students at a university in Arkansas during August‐December 2018. Face‐to‐face interviews using a validated questionnaire were employed to collect the data. BMI was calculated based on the self‐reported height and weight. Perceptions regarding weight were elicited using two questions: “Do you consider yourself to be underweight, overweight, or about right”? And, “if overweight, do you consider yourself to be obese or not?” The association between self‐reported BMI and weight perception was assessed with Chi‐Square tests for males and females. Level of significance was set at 0.05.ResultsData are presented as mean ± SD. Total 126 undergraduate students participated in the study, 86 males and 36 females. Descriptive statistics showed BMI of 27.07 ± 5.61 kg/m2 in males and 25.69 ± 4.52 kg/m2 in females. Majority of students reported a BMI range of normal weight which is 18.5–24.9 kg/m2 (88.9% of males, 72.2% of females). Out of the total males who self‐reported normal BMI, 3.7% considered themselves underweight and 7.4% considered overweight (χ2 = 33.6, p = 0.000). On the other hand, females who reported normal BMI, 16.7% considered themselves underweight and 11.1% considered overweight (χ2 = 13.250, p = 0.01). Among males who considered themselves overweight, 74.1% did not perceive themselves as obese (χ2 = 51.7, p = 0.000). On the other hand, among females who considered themselves overweight, 78.6% did not perceive themselves as obese (χ2 = 5.7, p = 0.677).ConclusionResults show that the average BMI is higher for males as compared to females. Weight standards are rather uniform between males and females, with female students more likely to perceive themselves as overweight and underweight at a normal BMI range. Furthermore, among males and females who perceived themselves as overweight, most of them do not consider themselves as obese. These findings are important for future primary and secondary prevention efforts. The gender differences advocate the need for gender‐tailored intervention programs.Support or Funding InformationDepartment of Health & Physical Education, Arkansas Tech University, Russellville, ARThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Tumor microenvironment regulates endothelial cell transformation via modulation of TRPV4 channels
Authors: Guarino Brianna D , Adapala Ravi K , Kanugula Anantha K , Lenkey Nina M , Paruchuri Sailaja , Thodeti Charles K 
Published: June 2021

Abnormal angiogenesis and hyper‐permeable vessels characterize the tumor vasculature. Together, these attributes contribute to atypical growth rate and metastasis of tumor cells. We have recently shown that the mechanosensitive ion channel, transient receptor vanilloid 4 (TRPV4) expression and activity is significantly reduced in tumor endothelial cells (TEC), and that activation of TRPV4 normalized tumor vasculature and improved cancer therapy. However, whether and how the tumor microenvironment downregulates TRPV4 and transforms normal endothelial cell phenotype remains unknown. To explore this, we repeatedly exposed normal human endothelial cells (NhEC) to human lung adenocarcinoma (tumor) cell conditioned media and measured phenotypic changes, angiogenesis, and functional expression of TRPV4. We found that treatment with cancer cell conditioned media changed NhEC to a tumor endothelial‐like phenotype (ThEC) as evidenced by; increased expression of tumor endothelial cell marker 8 (TEM8) and exhibition of abnormal angiogenesis on 2D‐Matrigels compared to normal NhEC. Mechanistically, we observed that expression and activity of TRPV4 was reduced in ThEC. Finally, we found that treatment with a Rho kinase inhibitor, Y‐27632 normalized abnormal tube formation exhibited by ThEC. Taken together, our results suggest that the tumor microenvironment transforms normal endothelial cells into tumor endothelial cell‐like phenotype through the downregulation of TRPV4.Support or Funding InformationNIH (1RO1HL119705), NIH (1R15CA202847‐01), and start‐up funds from NEOMED (CKT).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effect of a high fat diet in the regulation of MAP kinase in left ventricle fibrosis
Authors: Cudnoch‐Jedrzejewska Agnieszka , Czarzasta Katarzyna , Koperski Lukasz , Segiet Agnieszka , Fus Lukasz , Gornicka Barbara 
Published: June 2021

IntroductionIt is well known that obesity contributes to the development of systemic inflammatory responses, which in turn may be involved in the process of interstitial fibrosis and left ventricular (LV) remodeling. Activation of proinflammatory factors such as transforming growth factor β (TGF‐β) can directly stimulate mitogen‐activated protein kinase (MAPK) p38 and JNK.PurposeThe aim of this study was to evaluate the level of TGF‐β, MAPK p38 and JNK in the LV in Sprague Dawley (SPRD) rats maintained on a high fat diet (HFD).MethodsThe SPRD rats were maintained on a normal fat diet (NFD) or on a HFD from 4 weeks of age for 12 weeks (NFD 16‐week‐old rats, NFD 16‐wk; or HFD 16‐week‐old rats, HFD 16‐wk) or for 16 weeks (NFD 20‐week‐old rats, NFD 20‐wk; or HFD 20‐week‐old rats, HFD 20‐wk). At the end of the experiment, blood and LV were collected from all rats for further analysis (Real‐Time PCR, histopathological and immunohistochemical analysis). Consent was obtained from The Local Animal Research Ethics Committee (33/2011).ResultsThe LV fibrosis area in relation to the entire LV area was significantly higher in the HFD 16‐wk rats and the HFD 20‐wk rats compared with the NFD 16‐wk rats and the NFD 20‐wk rats, respectively. TGF‐β mRNA expression did not differ between the study groups of rats. However, p38 MAPK mRNA expression and c‐jun mRNA expression were significantly lower in the HFD 20‐wk rats than in the HFD 16‐wk rats. TGF‐β type II receptor (TβRII) protein demonstrated only cytoplasmic reactivity, while p38 MAPK protein and c‐jun protein showed both nuclear and cytoplasmic reactivity. The p38 MAPK nuclear reaction did not differ significantly between the study groups of rats. In contrast, the cytoplasmic response of the p38 MAPK was dependent on the administration of both HFD in two time intervals to the groups of rats. Significant differences in the nuclear reaction for c‐jun were observed between the exanimated groups of rats. The c‐jun nuclear expression was significantly lower in the HFD 20‐wk rats than in the HFD 16‐wk rats.ConclusionA high fat diet caused an increase in LV fibrosis in SPRD rats. Additionally, extension by the next 4 weeks the duration of HFD intake did not increase the LV fibrosis area. Moreover, high fat diet in both intervals significantly influences the expression of p38 MAPK and JNK in the LV. However, demonstrating their potential involvement in the processes of interstitial myocardial fibrosis and left ventricular remodeling requires further research.Support or Funding InformationThis study was financially supported by statutory funds from the Medical University of Warsaw (1MA/N/2018).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Vascular Action of Insulin in Pregnancy
Authors: Reyes Betzabel Rodríguez , Pérez Muñoz Eduardo I , López Mayorga Ruth M , Lugo Rosa Amalia Bobadilla 
Published: June 2021

Physiological insulin resistance associated with pregnancy is attributed to the increase of anti‐insulin hormones such as placental lactogen and p85 (potent negative regulator of PI3K), human growth hormone, TNFα, as well as adipokines. Besides, AT1 receptor for angiotensin II has a clear role in insulin resistance while the role of AT2 receptors is not well understood. On the other hand, it has been described an increased vascular expression of AT2 receptor during pregnancy. On the other hand, insulin has shown a PI3K‐AKT NO mediated vasodilator effect that may contribute to its metabolic actions. Therefore, the aim of this study was to evaluate if pregnancy decrease in the vasodilatory action of insulin and AT2 receptors participation in this change. Using a conventional isolated organ preparation, the vasodilator effect of cumulative concentrations of insulin was evaluated in rat aortic rings pre‐contracted with phenylephrine. Vasorelaxation of aorta rings was compared at day 14 and day 20 (term) of pregnancy in the presence and absence of the AT2 receptor antagonist PD123319. Pregnancy produced resistance to insulin induced vasodilatation in the thoracic aorta while the vasodilator effect increased in the abdominal aorta only in rings with intact endothelium. AT2 receptors participation on the insulin induced vasodilation was more evident on day 14 (half) gestation. These results suggest that the vascular action of insulin is enhanced by the participation of AT2 receptors for angiotensin II. Also, that both insulin action and AT2 receptor participation during pregnancy depend on the vascular territory studied.Support or Funding InformationSIP Instituto Politécnico Nacional, COFFAAThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.