bluuebunny/crossref_metadata_2025_split huggingface dataset:
α‐Tocopherol absorption into a three‐dimensional human skin tissue model
Authors: Evans Julie A , Garlick Jonathan , Johnson Elizabeth J. , Wang Xiang-Dong , Chen C-Y. Oliver 
Published: June 2021

Backgroundα‐Tocopherol (AT) is an important antioxidant for skin health. An in vivo‐like model is needed for evaluation of the bioactions of AT.ObjectiveThis study aimed to determine the feasibility of AT uptake in a 3‐dimensional (3D) human skin model.Methods and MaterialsAT was applied to media (0–25 μM) or topically (0–1 mg/cm2) for up to 48 h. Skin absorption of AT was quantified in dermis and epidermis by RP‐HPLC with UV detection after proteolysis and standard lipid extraction.ResultsOver a 48 h medium incubation with AT (25 μM), dermal and epidermal concentrations of AT increased to approximately 3 and 30 ng/mg wet weight, respectively. Over a 48 h topical incubation with AT (1 mg/cm2), concentrations of AT in the dermis were 0.4 μg/mg wet weight and increased in the epidermis to approximately 27 μg/mg wet weight. After 48 h incubation with 15 μM AT, dermal and epidermal concentration of AT were 1 and 21 ng/mg wet weight, respectively.ConclusionsOur 3D skin tissue model is a feasible tool to assess AT absorption into dermal and epidermal compartments. AT absorption into this model was time and dose‐dependent with concentrations reaching those found in vivo. This model allows for further investigation into the photoprotection and mechanisms by which nutrition may play a role in skin health. Support: USDA#581950‐7‐07; Almond Board of California
Quercetin decreases tumorigenesis in a high fat diet‐enhanced mouse model of breast cancer
Authors: Steiner Jennifer , Davis J Mark , McClellan Jamie , Green Jeffrey , Murphy E Angela 
Published: June 2021

Consumption of a high fat diet (HFD) increases the risk for breast cancer (BrCa). Bioactive food components such as quercetin (Quer) may target processes relevant to HFD‐enhanced BrCa.OBJECTIVETo determine the efficacy of Quer in prevention of HFD‐enhanced tumorigenesis in the C3(1)SV40Tag mouse model of BrCa.METHODSFemale C3(1)SV40Tag mice were assigned to a dietary treatment group (n=14–15) at 4wks of age: control (CON) diet (AIN76A; 11% kcal fat), HFD (41% kcal fat), or HFD supplemented with 0.02% Quer (QHFD). Body weight (BW) and food intake were measured weekly and palpable tumors bi‐weekly. At 18wks of age mice were sacrificed and all visible tumors were counted, and measured. Tumors were analyzed for mRNA expression of pro‐tumoral factors (VEGF, IL‐6, CD206 and TNF‐á) using RT‐PCR.RESULTSHFD intake (HFD and QHFD) significantly increased BW (wks 8–18) (P<0.05), despite no differences in kcal intake. Tumor number and volume were increased following HFD at 18wks and Quer offset this effect (P<0.05). In fact, QHFD mice had significantly lower tumor volume than CON at 18 wks. Tumor expression of VEGF, IL‐6, CD206 and TNF‐á all showed strong trends of an elevation in HFD compared to CON and QHFD.CONCLUSIONSThese data provide strong support for a beneficial effect of Quer in reducing HFD‐enhanced BrCa that may be mediated by its ability to decrease pro‐tumoral factors within the tumor.Grant Funding Source : None
Bioactive tomato components inhibit cancer promoting activity of testosterone in the mouse prostate epithelium
Authors: Tan Hsueh-Li , Elsen Amy C. , Erdman John W. , Thomas-Ahner Jennifer M. , Clinton Steven K. 
Published: June 2021

We hypothesize that tomato phytochemicals, such as lycopene (LYC), may antagonize cancer promoting testosterone activity in the normal prostate. C57/BL6 male mice (4 wks; n=84) consumed a control AIN93G or an identical diet with 10% tomato powder (TP) or 0.04% LYC beadlets. Mice were randomized to intact, castration, or castration + testosterone at 8 wks. Serum LYC analysis was by HPLC and prostate proliferation (Ki67) and apoptosis (ApopTag) were evaluated. Prostate gene expression was by qRT‐PCR. Serum LYC concentrations were 366 nmol/L for TP and 371 nmol/L for LYC and were reduced by castration (−38% in TP, P=0.02; −42% in LYC, P<0.001). Epithelial proliferation in TP and LYC fed intact mice was reduced by 50% (P<0.001) with a 30% inhibition (TP, P=0.02; LYC, P<0.001) observed in the castrate‐testosterone mice. Castration dramatically enhanced apoptosis which was further increased by TP (2.2%, P<0.05). CMO1 expression is present in the liver and not detected in the prostate. The CMO2 gene, present in the liver and potentially involved in eccentric LYC cleavage, was detected in the prostate and reduced by castration (P=0.005) with no effect of diet. Tomato phytochemicals may inhibit early prostate carcinogenesis by impacting androgen signaling pathways that impact sensitivity to early steps in the carcinogenic process. Testosterone may impact CMO2 gene expression suggesting a diet and endocrine interaction.Grant Funding Source: NIH‐NCI/AICR
Quality Characteristics of Korean Traditional Pancake(Jeon) Containing Blueberry for the Global Marketing as a Functional Food
Authors: jung ji-hye , yang jinyoung , park junghyun , shin junghee , kim hyunsook 
Published: June 2021

Korean traditional pancake, a popular traditional food, is often consumed as a side dish in Korea. However, it is very calorific and contains a lot of sodium so not ideal for people with overweight. We attempt to develop functional Korean traditional pancake low in calorie, with a good taste for the world. The Korean traditional pancake was made with blueberry(0% BBP, 16.5% BBP, 22.5% BBP). To exam the quality characteristic, nutritive components, total polyphenol and antioxidant activity(2,2‐diphenyl‐1‐picrylhydrazyl( DPPH) radical scavenging activity, Oxygen Radical Absorbance Capacity(ORAC) activity) were measured. The amount of calorie and sodium were decreased in a dose dependent manner(0% BBP; 177.16 kcal/448.93 mg, 22.5% BBP; 122.2 kcal/288.87 mg). Total contents of polyphenol were significantly high in 22.5% BBP(220.05 ± 10.98 mgGAE/100g sample) and the lowest in 0% BBP(67.61 ± 1.61 mgGAE/100g sample). The DPPH activity was the highest value of 62.81 ± 0.74% in the 22.5% BBP. As the results, this study showed that Korean traditional pancake containing blueberry decreased the calorie, sodium and improved antioxidant enzyme activity. This work was supported by Korean Food Foundation and BK 21.Grant Funding Source: Korean Food Foundation
Flavanols exert cardiovascular health benefits in humans by altering gene transcription levels in white blood cells
Authors: Weseler Antje R. , Ruijters Erik J. B. , Milenkovic Dragan , Haenen Guido R. M. M. , Bast Aalt 
Published: June 2021

Epidemiological evidence highlights that a diet rich in flavanols reduces the risk of cardiovascular disease. The molecular mechanisms by which flavanols establish their vascular health effects in humans are still not fully clear.In a randomized, double‐blind, placebo controlled study gene transcription levels were determined in white blood cells of male smokers before and at the end of the 8‐weeks supplementation of daily 200 mg of monomeric and oligomeric grape‐seed flavanols. Upon approval by the Medical Ethical Committee of the Maastricht University and Academic Hospital Maastricht, The Netherlands, the study was conducted in accordance with the World Medical Association Declaration of Helsinki of 1975 as revised in 2008.Flavanols significantly altered expression of genes mediating inflammation, redox processes, lipid metabolism and endothelial homeostasis. The beneficial regulation of transcriptional pathways involved in the pathology of cardiovascular diseases is suggested a major subcellular mechanism by which flavanols sustain vascular health in humans.
Effects of Combinations of Metyrapone and Oxazepam on Methamphetamine Cue Reactivity and the HPA Axis in Rats
Authors: Miller Andrew Joseph , Cornett Elyse , Guerin Glenn , Goeders Nick 
Published: June 2021

METH is a highly addictive psychostimulant. There is currently no FDA approved treatment for METH addiction. Study in our lab focuses on the role of the stress response and the influence of environmental cues in accounting for the high rate of relapse in recovering addicts (60% relapse for METH patients).The combination of Metyrapone (MET, a CORT synthesis inhibitor) and Oxazepam (OX, a benzodiazepine) has been shown to decrease both cocaine self‐administration and cue‐induced reinstatement. The MET/OX combination was used in these experiments to test its effects on cue‐induced METH craving in rats.Rats were trained to self‐administer METH via lever response. Drug delivery was paired with a tone and the illumination of a houselight, both serving as secondary reinforcers, or cues. After stable self‐administration of METH for at least 10 days, subjects entered a 2‐week abstinence period. Rats were then given a cue reactivity test wherein the cues were presented at lever response, but no METH was delivered. With vehicle pretreatment, the response‐contingent presentation of the cues reliably maintained METH seeking (i.e. lever responses). Pretreatment with the MET/OX combination attenuated responding at both doses tested, suggesting diminished craving. Levels of stress hormones corticosterone (CORT) and ACTH were measured to ensure that the MET/OX combination did not cause adrenal insufficiency.
Evaluation of aminoglycosides‐induced cardiotoxicity in zebrafish obtained in a low cost facility
Authors: Vargas Rafael Antonio 
Published: June 2021

Zebrafish is a popular model in basic medical sciences research since middle eighties. Cardiovascular research has been made in larvae and adults and different aspects of cardiovascular development and physiology has been described. Zebrafish heart is sensible to external chemicals agents and cardiac alterations in shape and function could be observed under conventional microscopy.Currently, we describe the set up of a low cost, custom‐built facility to produce zebrafish. In addition, we explore toxicity of aminoglycosides on cardiac activity of transparent zebrafish larvae. We have found that some aminoglycosides can cause arrhythmic activity at high doses. This effect has some similarities to the arrhythmogenic effect caused by classical antiarrhythmic drugs.Use of zebrafish as a model to investigate pharmacological and toxicological properties of different drugs could be an inexpensive, an ideal model, which could be an advantage for researchers in undeveloped countries where to obtain financial aid, in many cases, is too complicated.
Nitric Oxide Synthase, But Not Heme Oxygenase, Mediates The Adenosine A2B Receptor‐Sensitive Renal Vasodilations In Female Rats
Authors: El-Mas Mahmoud M , El-Gowelli Hanan M , Elsalakawy Lamiaa K , El-gowilly Sahar M 
Published: June 2021

Stimulation of adenosine receptors by 5′‐N‐ethylcarboxamidoadenosine (NECA) dilates the renal vasculature. Studies were conducted in phenylephrine‐preconstricted isolated perfused kidneys of female rats to determine: (i) the relative contributions of adenosine receptor subtypes to NECA responses and (ii) the potential modulation of these responses by nitric oxide synthase (NOS) and/or heme oxygenase (HO). Cumulative bolus injections of NECA (1.6–50 nmol) elicited dose‐related vasodilations. NECA responses were attenuated after blockade of A2B (alloxazine) but not A2A [8‐(3‐Chlorostyryl) caffeine] or A3 (VUF 5574) receptors, suggesting preferential involvement of A2B receptors in NECA vasodilations. NOS activation appears to mediate the A2B‐dependent NECA response because: (i) NOS inhibition by L‐NAME attenuated NECA responses, (ii) no additional inhibition of NECA responses occurred upon concurrent exposure to L‐NAME and alloxazine, and (iii) L‐arginine abrogated the alloxazine‐evoked inhibition of NECA responses. Conversely, HO inhibition by zinc protoporphyrin affected neither NECA responses nor the attenuating effect of alloxazine on these responses. Overall, the activation of A2B/NOS signaling underlies the vasodilatory effect of NECA in female kidneys.This project was supported financially by the Science and Technology Development Fund (STDF), Egypt, Grant No. 502.
AMP‐activated protein kinase activation is associated with an inhibition of fibrotic properties of cardiac fibroblasts
Authors: Horman Sandrine , Noppe Gauthier-Thibaut , Buchlin Patricia , Marquet Nicolas , Baeyens Nicolas , Morel Nicole , Vanoverschelde Jean-Louis , Bertrand Luc , Beauloye Christophe 
Published: June 2021

PurposeWe asked whether cardiac fibroblast (CF) function might be regulated by AMP‐activated protein kinase (AMPK). We also investigated cardiac fibrosis in AMPK knockout mice (KO) after myocardial infarction.MethodsCF were treated by Transforming growth factor‐beta‐1 (TGF‐beta‐1), serum or platelet derived growth factor (PDGF‐BB) to stimulate myodifferentiation, proliferation and migration respectively. AMPK was activated prior to the different treatments with thienopyridone derivative A‐769662. For in vivo studies, KO mice and their wild‐type (WT) littermate were submitted to a ligation of the coronary artery to mimic myocardial infarction. Gene expression in the left ventricule was measured by qRT‐PCR.ResultsA‐769662 compound dose‐dependently prevented TGF‐beta‐ 1‐induced myodifferentiation. In addition, it decreased by 50% proliferation and completely prevented PDGF‐induced migration of CF, without affecting their mortality. Studies in KO mice show that RNA expression for collagen I and III was significantly increased in the infarct area of KO mice compared to WT mice, after myocardial infarction.ConclusionOur data indicate that AMPK could be a negative regulator of CF function, and by this way decrease the fibrotic component of ventricular remodelling which takes place after myocardial infarction.
Distinct atrial and ventricular microRNA changes in experimental heart failure
Authors: Chen Yu , Wakili Reza , Luo Xiaobin , Naud Patrice , Kaab Stefan , Dobrev Dobromir , Nattel Stanley 
Published: June 2021

Heart failure (HF) causes different forms of remodeling in left atrium (LA) vs left ventricle (LV), with fibrosis much more prominent in LA. MicroRNAs (miRs) are central regulators in cardiac remodeling. This study compared LA and LV miRNA changes during the development of experimental HF.MethodsHF was induced in dogs by ventricular tachypacing (VTP, 240 bpm) for 0 (CTL), 12, 24 hrs, 1, 2 and 5 wks (n=5–8/group). MiR expression was assessed by microarray and qPCR.ResultsMicroarrays showed greater changes in LA vs LV (Fig A). MiR‐29b, miR‐133a and miR‐30a decreased within 24 hrs; MiR‐21 and miR‐146b increases started at 1 wk only in LA (B, C). In contrast, miR‐214 and miR‐146a showed similar changes in LA and LV (D). MiR‐21, miR‐29b, miR‐133 and miR‐30 are implicated in extracellular‐matrix (ECM) remodeling. Collagen‐1/ ‐3, fibronectin 1 and fibrillin increased ~3.8–26‐fold*** to steady state at 1–2 wk, TIMP‐3 decreased from 24 hrs (~58%***) while MMP‐9 increased at 12 hrs (~9‐fold***) and remained elevated. Changes were much smaller in LV at all times, agreeing with atrial‐predominant fibrosis. miR‐214 and miR‐146 target IKs and ICa,L subunits, known to change in HF LA and LV.ConclusionsVTP‐induced HF causes greater miRNA changes in LA vs LV. LA expression of miRs with effects on ECM synthesis, paralleled by related ECM expression changes, implicate miRNAs in HF related LA‐selective structural remodeling.
Rap1 and afadin promote interactions between adherens junctions and tight junctions and regulate endothelial permeability
Authors: Birukova Anna A , Zebda Noureddine , Wu Tinghuai , Dubrovskyi Oleksii , Sarich Nicolene , Birukov Konstantin G 
Published: June 2021

Oxidized 1‐palmitoyl‐2‐arachidonoyl‐sn‐glycero‐3‐phosphocholine (OxPAPC) enhances vascular endothelial barrier properties in vitro and in vivo. This study examined the role of small GTPase Rap1 and its downstream target afadin in regulation of OxPAPC‐induced interactions between adherens junctions and tight junctions, the major gatekeepers of endothelial barrier. Immunofluorescence analysis, subcellular fractionation, and co‐immunoprecipitation assays revealed OxPAPC‐induced translocation of cell junction adaptor protein afadin to the cell periphery. OxPAPC also promoted accumulation of adherens junction proteins: VE‐cadherin, p120‐catenin, and beta‐catenin and tight junction proteins: ZO‐1, occludin, and JAM‐A in the cell membrane. OxPAPC induced novel cross‐interactions between adherens junction and tight junction protein complexes, which were dependent on the OxPAPC‐induced Rap1/afadin activation. Inhibition of Rap1 or afadin function suppressed OxPAPC‐mediated endothelial barrier enhancement as well as it inhibited protective effects of OxPAPC against ventilator‐induced lung injury in vivo. These results show the critical role of Rap1/afadin‐mediated interactions between adherens junction and tight junction complexes in the pulmonary vascular endothelial barrier preservation.Funding: NHLBI HL089257, HL107920, HL76259, HL58064, HL89257
Estimating Water Loss During Hibernation in the American Black Bear (Ursus americanus)
Authors: Howard Stephen Andrew , Rothstein Krista , Laske Timothy G , Garshelis David L , Iaizzo Paul A 
Published: June 2021

The American black bear can hibernate for up to 6 months. During this period they do not eat, drink, urinate, or defecate: they elicit minimal movements and typically do not leave their dens. Still, they lose minimal skeletal muscle mass and strength, and do not suffer any adverse consequences of either starvation or dehydration. In previous reports bears have been shown to maintain normal blood compositions, suggesting that they sustain homeostasis of their blood and other bodily fluids. To maintain this water balance without any fluid intake, bears must minimize water loss throughout their bodies, including their respiratory systems.Radio‐collared wild black bears in northern Minnesota were tracked to their dens during early or late hibernation. Bears were anesthetized, after which the relative amount of water vapor expired was analyzed using a hygrometer/mask system. We designed a respiratory mask to fit on the muzzle of the bear to collect expired air while still allowing them to breathe normally. From these data we estimated the amount of water vapor lost by bears during hibernation and were able to estimate that a 200–250 lbs bear would lose only 2.3L of water in 5 months of hibernation. This ability to conserve water during respiration is required to sustain long periods without intake through diet or drinking. Funding by NIH training grant 5T32AR007612 and Medtronic professorship funding.
Absolute quantification of muscle glycogen content in patients with glycogen storage disease by 13C NMR spectroscopy at 7 Tesla
Authors: Heinicke Katja , Dimitrov Ivan , Cheshkov Sergey , Malloy Craig R. , Haller Ronald G. 
Published: June 2021

ObjectiveEvaluate the invivo muscle glycogen content in patients with glycogen storage disease by performing noninvasive 13C NMR spectroscopy in ultra‐high fields with the advantages of improved signal‐to‐noise ratio and spectral resolution.MethodsMuscle glycogen content was measured in 3 patients with McArdle disease (MD), 1 phosphofructokinase deficient (PFKD) patient, and 4 healthy controls (C). 13C spectra were acquired on a whole‐body 7T scanner (Philips Medical) using a partial volume human calf coil operating in quadrature for 1H and 13C. The coil had a small vial of acetate fixed inside, to serve as an external reference for quantification. For absolute quantification, a 1L cylindrical phantom was prepared with 100 mM glycogen, and 40 mM creatine.ResultsMuscle glycogen concentration was increased in MD (184.7±14.9 mM) and PFKD (196.0 mM) compared with C (73.1±13.0 mM). Creatine concentration and glycogen/creatine ratio respectively were 82.2±21.9 mM and 2.3±0.6 in MD, 120.5 mM and 1.6 in PFKD, 74.5±8.3 mM and 1.0±0.3 in C. T1 values, the strongly field dependent relaxation times, were established at 7T for glycogen 3.1±1.4 s and creatine 8.8±5.7 s in MD, 0.8±0.4 s and 2.0±1.4 s in C, respectively.ConclusionsMuscle glycogen concentration was 2.5‐fold increased in patients with glycogen storage disease. Noninvasive ultra‐high filed 13C NMR spectroscopy may provide a valuable tool to study glycogen storage in progression of the pathology and efficacy of treatment.Study supported by Muscular Dystrophy Association and Giant Tiger Foundation.
Differential Responses of Genes for Neurosecretory Granules in the Rat Adrenal Medulla to Acute and Repeated Stress
Authors: Sabban Esther Louise , Tillinger Andrej , Serova Lidia I , Nostramo Regina 
Published: June 2021

With acute stress, release of adrenomedullary catecholamines is important for handling the emergency situation. However, when chronic or repeated, stress leads to development or worsening of wide range of diseases. To clarify the mechanism, we studied changes in components of neurosecretory granules in adrenal medulla of male Sprague Dawley rats exposed to immobilization stress for 2 h once (1xIMO) or for 6 days (6xIMO). While vesicular monoamine transporter 1 (VMAT1) was expressed in all chromaffin cells, VMAT2, which has greater affinity for catecholamines, and higher turnover number than VMAT1, was expressed only in the NE‐cells under basal conditions. 1xIMO elevated VMAT2 mRNA, and after 6xIMO, this was reflected in nearly 3‐fold rise in VMAT2 protein, and expression in many Epi‐synthesizing cells. With 6xIMO, not only was VMAT2 mRNA still elevated, but chromogranin A (CgA) and chromogranin B (CgB) mRNAs were also increased 2–3 fold. The elevation of CgA, CgB and VMAT2 are each expected to increase the quantal size. This can facilitate more efficient use of the well characterized heightened catecholamine levels. To investigate a possible role of the HPA axis in induction of VMAT2, PC12 cells were treated with dexamethasone, which elevated VMAT2 mRNA expression. In contrast, the rise in Egr1 and P‐CREB may mediate the induction of CgA and CgB with repeated IMO stress.American Heart Association 10GRNT4420001
Role of interstitial nodal spaces in the urine concentrating mechanism of the rat kidney
Authors: Gilbert Rebecca L , Pannabecker Thomas L. , Layton Anita T. 
Published: June 2021

Recent findings in the upper inner medulla of the rat kidney indicate thin limbs of Henle's loops and vasa recta are arranged in repeating patterns among clusters of collecting ducts (CDs). Within CD clusters an interstitial compartment (interstitial nodal space INS) can be seen in transverse sections of the inner medulla. INSs are delimited by a single CD, one or more ascending thin limbs (ATLs) and ascending vasa recta (AVR). In this study we investigated possible fluid and solute flows among CDs, ATLs and AVR, by examining the spatial interactions of structures that form the INSs. Nephron tubules and vasa recta were identified using immunohistochemistry. Spatial interactions were assessed by quantifying lengths of abutting segments of the rat inner medulla. INS architecture was incorporated into a mathematical model simulating steady‐state solute exchange through INSs at given inner medullary levels. At 400 μm below the outer medullary‐inner medullary border approximately 70% of CD was found to abut the INS. In the INS there are negative fixed charges representing macromolecules, e.g. hyaluronan, balanced by Na+ that may promote water reabsorption from CDs. Model results quantify potential fluid and solute fluxes between INSs, nephrons and vessels, and support the hypothesis that INSs serve as fluid and solute mixing chambers that support the inner medullary osmotic gradient.NIH: DK083338 and NSF: DMS0701412