bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regular consumption of apples may promote cardiovascular health
Authors: Chai Sheau C , Saadat Raz L , Hooshmand Shirin , Arjmandi Bahram H 
Published: June 2021

Decline in estrogen levels in postmenopausal women is associated with unfavorable changes in lipid profiles and markers of inflammation placing them at a higher risk for cardiovascular disease (CVD). The present short‐term study examined the effects of daily consumption of 75 g dried apples on lipid profiles, independent atherogenic risk factors including lipoprotein (a) [Lp(a)] and high‐sensitive C‐reactive protein (hs‐CRP), in postmenopausal women. Fifty‐five postmenopausal women not on hormone replacement therapy consumed 75 g of dried apple daily for three months. Overnight fasting blood was collected at baseline and at the end of three months. The findings suggest that CVD protective effect of apple consumption is beyond improving lipid profiles (TC, LDL‐C, and TG) as evident by significant reductions in serum levels of Lp (a) (21±3.2 vs. 19±3.1 ) and hs‐CRP (1.8±0.16 vs. 1.3±0.17). Future studies are warranted to investigate the long‐term favorable effects of apple or its bioactive components consumption in improving endothelial function which is compromised as a result of aging.Grant Funding SourceAbstract submitted to the competition shall just have a title and the abstract body and nothing else
Processed tomatoes on vasodilatation and C‐reactive protein (hsCRP) in overweight and obese men and women
Authors: Giordano Rose M , Kappagoda Tissa , Cheema Mandeep , Cappozzo Jack , Cao Yumei , Kris‐Etherton Penny , Burton‐Freeman Britt 
Published: June 2021

BACKGROUNDInflammation and endothelial dysfunction are targets for lowering disease risk with dietary strategies. We tested the effect of tomato products known for their lycopene content, on inflammation and endothelial function (EF).METHODSProcessed tomato‐ or non‐tomato products matched in energy, sodium, and sugar content (high tomato HT, 5 servings/d vs low tomato LT, <1 servings/d) were included in the diets of 56 free‐living individuals (Age=44±12 yr, F=35, M=21) and tested in a multi‐center, randomized, controlled trial. All subjects had a 3wk LT run‐in followed by either 6 wk HT or LT diet. A random subset of 23 subjects had 3 postprandial (6hr) visits; at wks ‐2, ‐3 (run‐in) and at 6 wk to assess the acute and residual affects of tomato after a high fat meal (HFM). Endpoints were hsCRP and flow mediated vasodilatation (FMD).RESULTSTomato had no acute effect on hsCRP after the HFM during run‐in. However, after 6 wk HT vs LT, hsCRP was lower in response to HFM (HT:1.98 0.15, LT:2.930.27 mg/L, p=0.013). HT was associated with increased mean vessel diameter (p=0.03); however FMD was not different, possibly related to BMI (BMI by diet interaction, p=0.01).CONCLUSIONThese findings suggest that processed tomatoes provide a protective role on inflammation; increasing adiposity may negate the benefits of diet on EF. Study sponsored by the Tomato Products Wellness Council.
Almond skins digestion: release of phytochemicals and gut health.
Authors: Mandalari Giuseppina , Rich Gillian T , Bisignano Giuseppe , Parker Mary L , Waldron Keith W , Wickham Martin SJ 
Published: June 2021

Almond skins (Amygdalus communis L.) contain high‐value components, such as dietary fibre and polyphenols. Here we describe the bioaccessibility of phytochemicals from almond skins during gastrointestinal (GI) digestion and the role of cell walls in regulating bioaccessibility. A dynamic gastric model of digestion which simulates the physical‐chemical processing of the stomach and accurately mimics both the transit time and the luminal content of the upper human gut was used to digest almond skins in vitro. No significant changes were observed in the sugar composition of the cell walls of almond skin after in vitro gastric or in vitro gastric + duodenal digestion, suggesting that no degradation of the dietary fibre had occurred. The decrease in the concentration of the major phenolics and flavonoids within the almond skins after digestion was used as a measure of their bioaccessibility in the GI tract. Under UV light, blue autofluorescence was emitted from the phenolics within the walls of the sclerenchyma cells, the lignified cells of the xylem, and from the cuticle overlying the nucellar layer. Phytochemicals from almond skins are bioavailable in the GI tract. The high dietary fibre content could be exploited for the potential health benefits of non‐glycaemic carbohydrate functional food preparations, mainly for gut health.This work has been funded by the Almond Board of California.
Pharmacokinetic study of the absorption and metabolism of Montmorency tart cherry anthocyanins in human subjects
Authors: Uhley Virginia Ellen , Seymour E Mitch , Wunder Jenna , Kaufman Peter , Kirakosyan Ara , Al‐Rawi Sara , Warber Sara 
Published: June 2021

Anthocyanins found in tart cherries have been shown to function as antioxidants and anti‐inflammatory agents. The in vivo bioavailability of anthocyanins from the ingestion of whole fruits or vegetables and their potential biologic effects have not been well characterized.This study was designed to investigate the pharmacokinetics of anthocyanins in healthy human subjects following the ingestion of a measured dose of tart cherries. We quantified five major anthocyanin compounds in Montmorency cherries as cyanidin 3‐glucosylrutinoside, followed by cyanidin 3‐rutinoside, cyanydin sophoroside, peonidin 3‐glucoside and pelargonidin for the estimation of the tart cherry dose. Samples from human subjects were collected at specified time points over a 14 hour time period. Our preliminary results indicate that anthocyanin metabolites can be identified and quantified in human blood and urine using Liquid Chromatography‐Mass Spectrometry (LC‐MS) analysis. The consumption of whole fruit tart cherries resulted in the appearance of two unmodified anthocyanins in plasma: cyanidin 3‐glucosylrutinoside and cyanidin‐3‐rutinoside, and three modified anthocyanins in urine: cyanidin‐xylosylxyloside, pelarogonidin‐xylosylxyloside, and methylated peonidin‐xylosyloside. In order to determine clinical relevance, further work is planned to evaluate the antioxidant capacity of human plasma after ingestion of tart cherries.
High fat diet induces airway remodeling in ApoE deficient mice: An association with an increase in circulatory and airway inflammatory factors
Authors: Naura Amarjit Singh , Hans Chetan , Zerfaoui Mourad , Errami Youssef , Ju Jihang , Kim Hogyoung , Matrougui Khalid , Boulares Hamid A 
Published: June 2021

ObjectiveTo examine the effect of high fat (HF) diet and associated hypercholesterolemia on airway integrity in mice.MethodsThe HF diet‐induced hypercholesterolemia and atherogenesis mouse (ApoE−/−) model was used to conduct the study.ResultsHF diet induced systemic production of inflammatory cytokines including TNF‐α, IFN‐γ, GMC‐SF, RANTES, IL‐1α, IL‐2, and IL‐12 in ApoE−/− mice with TNFα as the predominant cytokine. Concomitantly, TNF‐α, IFN‐γ, and MIP‐1α were detected in brochoalveolar lavage fluids of these mice, coinciding with airway inflammation consisting primarily of monocytes/macrophages. Such airway inflammation was associated with marked collagen deposition, an increase in MMP‐9 activity and TGF‐β distribution in lungs of HF‐fed ApoE−/− mice. Direct intratracheal TNFα‐administration induced an inflammation pattern in wild type mice similar to that observed in HF diet‐fed ApoE−/− mice suggesting that TNFα may be an important player in hypercholesterolemia‐induced airway inflammation. Indeed, TNFα administration induced expression of MCP‐1, IL‐1β, TGFα1, adhesion molecules, collagen 1 and TNFα itself in the lungs of treated mice, all of which are known to be important for airway remodeling.ConclusionThese results suggest that a HF diet and associated hypercholesterolemia may promote chronic inflammatory conditions in lungs that are conducive to airway remodeling.
Longitudinal Assessment Of The Modulatory Effect Of Estrogen On Blood Pressure And Cardiac Autonomic Activity In Female Rats
Authors: El‐Mas Mahmoud M , Abdel‐Rahman Abdel A 
Published: June 2021

Reported findings on the effect of ovarian hormones on hemodynamic variability are contradictory. In this study we employed radiotelemetric hemodynamic monitoring to investigate the long‐term effect of estrogen depletion and repletion on cardiac autonomic control and baroreflex sensitivity (BRS). Blood pressure (BP), heart rate (HR), and +dP/dtmax (index of myocardial contractility) were monitored in sham‐operated (SO), ovariectomized (OVX), and estrogen‐treated OVX (OVXE2) rats for 16 weeks. Cardiovascular autonomic control was assessed by frequency analysis of interbeat intervals (IBI) and systolic BP (SBP). Compared with SO, OVX rats exhibited sustained reductions in dP/dtmax despite similar BP and HR. High‐frequency (HF, 0.75‐3 Hz), but not low‐frequency (LF, 0.25‐0.75 Hz), bands of IBI were reduced in OVX rats, suggesting attenuated cardiac vagal activity. OVX increased IBILF/HF ratio, indicating increased sympathetic dominance. Indexα, spectral index of BRS, was reduced in OVX rats. E2 replacement decreased BP and HR and reversed the effects of OVX on dP/dtmax and cardiac autonomic activity. LF oscillations of SBP were reduced in OVXE2 rats, highlighting a reduction in vascular sympathetic tone.Conclusionslong‐term estrogen therapy rectifies the detrimental cardiovascular and baroreflex influences caused by depletion of ovarian hormones.Supported by Grant R01 AA014441 from NIAAA.
The Morphological Investigation Of The Mechanism Of Astragalus Polysaccharide Against Endoplasmic Reticulum Stress By Activation Of AMPK In TIID Rats
Authors: Zhao Ming , Ouyang Jingping 
Published: June 2021

OBJECTIVETo investigate the effects of Astragalus polysaccharide on reducing ER stress in a rat Model of Type 2Diabetes.Methods44 SD male rats were randomly divided into two groups, group A was fed with high fat forage and injected with small dosage STZ 25mg/kg through caudal vein, successful rat models were randomly divided into two groups: diabetes group DM group,DM +APS group.Group B were fed with normal forage and also randomly divided into two groups: control group (group C), control+APS (group C +APS group) ,C +APS group and DM +APS group were administered with APS 700mg/kg/day , while group C and DM group were administered with the same dose of Sodium Chloride for 8 weeks. The animals were killed at the end of 8 week treatment with APS,the expression of p‐PERK and p‐AMPK in liver tissue was detected by immunohistochemistry.Results1, The expression of p‐PERK was significantly increased in DM group as compared with the control group ,but the expression in DM +APS group was markedly lower than DM group 2,The expression of p‐AMPK was significantly decreased in DM group as compared with the control group, but the expression in DM group was markedly lower than DM+APS group.ConclusionAPS treatment can relieve ER stress through reducing the expression of phosphorylated PERK in a rat model of type 2 diabetes by activation of AMPK.
Differential effects of COX‐2 inhibitors on vascular smooth muscle cell function
Authors: Mackie Alexander R , Brueggemann Lioubov I 
Published: June 2021

Selective cyclooxygenase‐2 inhibitors (known as coxibs) are efficacious anti‐inflammatory drugs. Despite their efficacy, reports of off‐target cardiovascular effects of coxibs led us to investigate the effects of these drugs on vascular smooth muscle ion channels. The ability of various coxibs to influence KCNQ K+ and L‐type Ca2+ currents in rat mesenteric artery smooth muscle cells (MASMCs) was evaluated using perforated patch clamp techniques.ResultsVoltage clamp recordings of MASMCs revealed that celecoxib (10 μM) enhanced KCNQ currents two‐fold while rofecoxib and diclofenac (both at 10 μM) were without effect. Celecoxib also decreased L‐type Ca2+ channel maximal conductance three‐fold in MASMCs. Isolated artery pressure myography experiments revealed that celecoxib induced dose‐dependent dilation of rat mesenteric arteries (MAs) pre‐constricted with 100pM vasopressin. Endothelium‐denuded MAs also dilated in response to celecoxib, suggesting that this effect was endothelium‐independent. In separate experiments, celecoxib (20 μM) produced 97.6 ± 1.2% of dilation of MAs pre‐constricted with 100pM vasopressin, whereas rofecoxib and diclofenac (both at 20 μM) produced only 11.5 ± 2.5% and 5.8 ± 2.0% dilation respectively.Conclusioncoxibs display differential effects on vascular KCNQ and L‐type Ca2+ channels that may account for some off‐target cardiovascular effects. This work was supported by the AHA (0715618Z to ARM).
role of protein kinase C in 15‐HETE‐induced hypoxic pulmonary vasoconstriction
Authors: Zhu Daling , Guo Lei , Tang Xiaobo , Chu Xiaojie 
Published: June 2021

AbstractThe aim of the present study was to investigate the roles of protein kinase C (PKC) signal transduction pathways in the 15‐hydroxyeicosatetraenoic acid (15‐HETE)‐induced down‐regulated expression of KV1.5, KV2.1 and KV3.4, and pulmonary vasoconstriction under hypoxia. Tension measurements on rat pulmonary artery (PA) rings, Western blots, semi‐quantitative PCR, and whole‐cell patch clamp technique were employed to investigate the effects of 15‐HETE on PKC and KV channels. Hypericin (6.8 μmol/L), a PKC inhibitor, significantly attenuated the constriction of PA rings to 15‐HETE under hypoxia. The down‐regulation of KV1.5, KV2.1 and KV3.4 channel expression, and inhibition of whole‐cell K currents (IKV) induced by 15‐HETE were rescued, and restored, respectively, by hypericin. These studies indicate that the PKC signal transduction pathway is involved in 15‐HETE‐induced rat pulmonary vasoconstriction under hypoxia. 15‐HETE suppresses the expression of KV1.5, KV2.1 and KV3.4 channels and inhibits IKV through the PKC signaling pathway in pulmonary arterial smooth muscle cells.
Modulation of Synaptic Transmission by G Protein βγ Subunits
Authors: Betke Katherine , Wells Christopher , Lindsley Craig , Gao Alice , Marala Ravi , Hamm Heidi 
Published: June 2021

Synaptic transmission is characterized by exocytotic events which mediate the release of chemical transmitters to facilitate neuronal communication. Gi/Go coupled GPCRs play an important role in controlling exocytosis. In addition to direct interaction with voltage‐gated calcium channels to inhibit calcium influx, Gβγ subunits bind directly to SNARE proteins in the regulation of fusion events. The current study is aimed at developing small, druglike molecules which target the βγ /SNARE interaction to elucidate details involved in this novel mode of neuromodulation.Compound libraries were screened using a novel, label free detection method, Corning Epic®, which identifies protein‐protein interactions as changes in the local index of refraction due to binding events. Using these signals, we evaluated the ability of small molecules to modulate the Gβγ /SNARE interaction. Initial screening identified five lead compounds. By further application of an iterative analog library synthesis approach, we will develop analogs with improved physiochemical properties to serve as tools to dissect the therapeutic relevance of the Gβγ /SNARE interaction. This work was supported by the National Institutes of Health (EY010291).
Chemotherapy associated memory/learning loss and reversal with supplemental amino acids in a rat model
Authors: Morgan Lee Roy , Thornton Melissa E. , Benes Edmund , Luttrell Melody M , LaHoste Gerald J. , Jursic Branko S. 
Published: June 2021

IntroductionMost chemotherapy drugs (5‐FU, penclomedine (PEN), phosphamides) that alter memory are pyrimidines, pyridines or other pseudohetero‐cyclic rings that could interact with/antagonize the CNS N‐methyl‐D‐aspartate (NMDA)receptor complex ‐ a memory transmitter pathway. NMDA has numerous neurotransmitter substrates ‐ glutamate, serine, glycine, N‐methyl D‐spartate, all of which can also exist as pseudo‐pyridine or pyrroles. Agents that reverse the memory/learning deficiencies are described here.MethodsThe Morris water maze was modified to screen agents for behaviorial changes. Adult female rats were dosed IP once with PEN (100 mg/kg or 5‐FU (78 mg/kg) and compared vs. controls for learning/memory over 24 h. The time required for each rat to swim & find a pedestal was compared (6 consecutive swims ‐ avg/SD of the 1st vs 6th were compared). Either N‐acetyl cysteine (NAC)(200 mg/kg) or L‐lysine (50 mg/kg) was administered (PO) x 3 days pre‐chemotherapy. The results were compared with the NMDA binding assay in vitro in rat brain homogenates.ResultsPEN and 5‐FU had significant impacts on memory and learning with 1.5 & 2.5‐fold impairment, resp., after 3 hr., and >85% for PEN & 5‐FU at 24 h.,which continued for 1‐3 days, despite normal appearances. 5‐FU and PEN impairments were reversed 1.5 ‐ 2.3 fold with NAC and L‐lysine, resp.ConclusionDrugs that can exist in 5‐6 membered ring configurations could interact antagonize the NMDA receptor complex. NAC is a Lewis acid and L‐lysine a Lewis base, each reversing basic and acidic drugs, resp. The described behavorial screen is easy to use and could be useful in screening anti‐cancer agents for behavioral modification. Supported by NCI/SBIR grant ‐ 5R44CA85021.
Insulin‐like growth factor I (IGF‐1) downregulates lipoprotein lipase and suppresses atherosclerotic foam cell formation in vivo and in vitro
Authors: Sukhanov Sergiy , Vaughn Charlotte , Higashi Yusuke , Titterington Jane , Delafontaine Patrick 
Published: June 2021

We have shown that IGF‐1 decreases atherosclerosis in ApoE‐null mice. Lipoprotein lipase (LPL) increases the uptake of OxLDL by macrophages (MΦ), promoting foam cell formation and atherosclerosis development. To determine a potential effect of IGF‐1 on LPL and foam cell formation, we infused ApoE‐null mice with 1.5 mg/kg IGF‐1 or saline for 12w. IGF‐1 reduced aortic LPL mRNA levels by 31% (RT‐PCR) and serum LPL activity by 66% (fluorescence assay). This effect correlated with a 27% reduction in Oil Red‐positive lesion area and a 36% decrease in plaque MΦ (immunostaining with Mac‐3 a/b) suggesting that IGF‐1 reduced MΦ‐derived foam cell formation.Human blood monocyte‐derived MΦ were treated with 80 ug/ml OxLDL for 48h to stimulate formation of Oil Red‐positive "foam cells". OxLDL increased MΦ LPL mRNA levels and LPL activity >5‐fold. Pre‐treatment with IGF‐1 (25 ng/ml, 24h) reversed OxLDL‐induced upregulation of LPL activity by 52% and decreased lipid uptake by 88%. Furthermore, adenovirus‐mediated overexpression of IGF1 receptor in MΦ prevented lipid uptake by 82% vs. control Ad‐GFP‐infected MΦ. Conversely, addition of exogenous LPL (5 ug/ml) stimulated DiI‐OxLDL binding by MΦ by 2.3‐fold and increased lipid uptake by 1.9‐fold (Oil Red‐staining). Liver X receptor (LXR) is a nuclear transcription factor regulating MΦ LPL expression. The LXR agonist 22R‐oxycholesterol (50 uM, 16h) increased LPL activity in MΦ >2‐fold and IGF‐1 reversed this effect by 65%. In summary, our data indicate that IGF‐1 downregulates LPL in vivo and in vitro potentially via a LXR‐dependent mechanism and inhibits foam cell formation. This is the first report of an effect of IGF‐1 on cellular lipid internalization and these findings have major relevance for the understanding of mechanisms whereby IGF‐1 reduces atherosclerosis.
Development of an animal model of microvascular thrombosis
Authors: Calhoun William R , Kanth Shreya , Torres Filho Ivo 
Published: June 2021

We have developed a model of thrombosis to test in vivo the efficacy of antithrombotic agents in a microvascular network. The model involves the induction of a platelet thrombus within venules of the spinotrapezius muscle in anesthetized Sprague Dawley rats using a compound normally employed for microvascular oxygenation measurements (Pd‐tetra‐4‐carboxyphenylporphyrin). The photoactive chemical is injected intravascularly and is excited with a 532 nm pulsed, Er:YAG laser ( 8‐10 ?W, 0.4‐0.6 kHz). As a result, free radicals are formed causing injury to the endothelial wall, subsequent platelet aggregation and thrombus formation without microvascular constriction. Red blood cell (RBC) velocity and intravascular diameter at thrombus site are monitored periodically. After testing venules of different sizes and RBC velocities, the most repeatable data were gathered from venules with diameters ranging from 40 to 60 µm and with RBC velocities ranging from 2 to 4 mm/sec. Upon establishing these control parameters, the model is being used to induce local ischemia and to test the effects of injected anti‐thrombotic agents on platelet thrombus formation and local blood flow.Support: AD Willliams Trust Funds (VCU).
Human thermoregulation and obesity
Authors: de Graaf Albert Arjaan , Freidig Andreas , van Ommen Ben 
Published: June 2021

On average 80% of muscular physical activity energy has to be released by the body as heat. Obese people have a thick insulating fat layer. We investigated whether the concomitant thermal isolation can fundamentally limit heat dissipation and therefore exercise capacity in the obese.To estimate key values of thermoregulatory properties in humans, relevant mechanisms, models, their parametrization and data that were taken from the literature. Investigated thermoregulatory relevant properties and mechanisms included body heat capacity, clothing, sweating, vasodilation, respiratory evaporation, and body thermal resistance.We found that the most effective mechanisms for heat loss during exercise are vasodilation (increased tissue conductance) and sweating. Thermal insulation by the fat layer is effectively shunted by increased skin blood flow.Since muscle and skin compete for blood flow for energy supply and heat transport, respectively, we hypothesize that cardiac output and tissue/muscle blood flow are major players in thermoregulation in the obese. The available data suggest that in untrained obese, tissue conductance as well as sweating rate are significantly lower than in lean, fit people, with total heat loss capacity possibly limited to 350 W. It is concluded that thermoregulation may fundamentally restrict exercise performance in unfit obese.
Mechanical ventilation induces diaphragmatic mitochondrial oxidant production resulting in mitochondrial damage and respiratory dysfunction
Authors: Kavazis Andreas N , Talbert Erin E , Smuder Ashley J , Hudson Matthew B , Nelson W. Bradley , Powers Scott K 
Published: June 2021

Mechanical ventilation (MV) is a life saving intervention used in patients with acute respiratory failure. Unfortunately, prolonged MV results in diaphragmatic weakness which is an important contributor to the failure to wean patients from MV. We have shown that reactive oxygen species (ROS) play a critical role in diaphragmatic weakness following MV, but the pathways responsible for MV‐induced diaphragmatic ROS production remain unknown. We hypothesized that following MV diaphragmatic mitochondria produce higher rates of ROS resulting in mitochondrial oxidative damage and dysfunction. Our results support this hypothesis as mitochondria isolated from the diaphragm of MV rats possessed a lower respiratory control ratio compared to control. Further, MV diaphragmatic mitochondria produced higher rates of ROS in both state 3 and state 4 respiration. MV diaphragmatic mitochondria also exhibited higher levels of oxidative damage as indicated by increased lipid peroxidation and protein oxidation. Finally, our data also reveal that the activities of electron transport chain complex II, III, and IV are depressed in diaphragmatic mitochondria following MV. In summary, these results are consistent with the concept that diaphragmatic inactivity promotes an increase in mitochondrial ROS production resulting in mitochondrial oxidative damage and respiratory dysfunction.Supported by an NIH R01 awarded to SKP.