bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZnR/GPR39 mediated human salivary secretion
Authors: Kim Yoon‐Jung , Jo Youhwa , Jo Su‐Hyun , Park Hee‐Kyung , Choi Se‐Young 
Published: June 2021

Zn2+ is divalent cation that is essential for many biological events by affecting various ion channels. Zn2+ can serve G‐protein coupled receptor signaling via activation of metabotropic zinc receptors, ZnR/GPR39. In spite of several evidences of the existence of ZnR/GPR39 in salivary gland cells, there has been no evidence of ZnR/GPR39‐mediated modulation of the salivary gland functions. Here we have characterized the role of ZnR/GPR39 in human submandibular gland cells. Mouth wash with Zn‐containing solution evoked the secretion of unstimulated and stimulated whole saliva in human. We found that ZnR/GPR39 is expressed in the human submandibular glands and HSG cells. Zn2+ increased cytosolic Ca2+ concentration ([Ca2+]i) in a concentration‐dependent manner. Both muscarinic antagonist and histaminergic antagonists did not have any effect on Zn2+‐induced increase [Ca2+]i, which is completely blocked by the inhibitor of phospholipase C‐beta. Like as muscarinic and histaminergic stimulation, Zn2+ induced the translocation of aquaporin‐5 (AQP5) into the plasma membrane. These data suggest that metabotropic zinc receptors can modulate salivary secretion in human submandibular gland cells independently from the muscarinic receptor signaling.Support or Funding InformationThis work was supported by the National Research Foundation of Korea (2017R1A2B4002176 to H.K.P.; 2018R1A5A2024418 to S.Y.C.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
EFFECT OF INTERFERON‐γ ON THE NEUTROPHIL FUNCTIONAL PROPERTIES
Authors: Duarte Ana Paula Ferreira , de Souza Ivani Aparecida , Ramos Verônica Santos , Torres Anelize Sgorlon Pinheiro , Antunes Edson 
Published: June 2021

Interferon γ (IFN‐g) is a cytokine produced by natural killer T cells implicated in innate and acquired immune response during bacterial infections. Higher levels of this cytokine are suggested to suppress the hematopoiesis, leading to leukopenia that is clinically observed after the resolution of severe infectious. Evidence shows that IFN‐g induces MHC class II overexpression in human circulating neutrophils (NE) and reduces Staphylococcus aureus‐mouse induced NE infiltration. Our preliminary results have been showing that staphylococcal enterotoxins (SEs; type A and B) are able to inhibit human NE properties such as adhesion and chemotactic response. Whereas, IFN‐g release is reported to contribute to pathological events induced by SEs the aim of the present study was investigate the effect of IFN‐g on the functional properties of human NE. Blood was collected from healthy volunteers after approval from the local ethics committee (Protocol No 61370616.3.0000.5412). Blood samples were placed on isotonic Percoll solution. After centrifugation, the mononuclear cell layer was removed and the pellet containing erythrocytes and granulocytes was aspirated and subjected to isotonic lysis. After lysis cells (98% NE) were resuspended to 4 × 106 cells/ml and submitted to in vitro incubation with IFN‐g (10000 IU/ml; 30 min). Adhesion assays were carried out in 96‐well plates pre‐coated with recombinant human VCAM‐1 and ICAM‐1 for 30 min in the presence of interleukin‐8 (IL‐8). The NE adhesion was calculated by measuring myeloperoxidase (MPO) activity on adherent cells. NE migration assay was performed using a 48‐well microchemotaxis Boyden chamber. Prior NE in vitro incubation with IFN‐g reduces human NE adhesion in VCAM‐1 (Control: 4.7 ± 0.5; untreated NE + IL‐8: 6.7 ± 0.6; IFN‐g treated NE+IL‐8: 4.8 ± 0.66 optic density/NE × 106 cells; ) or ICAM‐1(Control: 4.3 ± 0.5; untreated NE + IL‐8: 6.1 ± 0.6; IFN‐g treated NE+IL‐8: 3.9 ± 0.48 optic density/NE × 106 cells) coated plates. Similar results were observed for NE chemotactic activity (Control: 18.7 ± 0.8; untreated NE +IL‐8: 52.9 ± 2.7; IFN‐g treated NE+IL‐8: 36.4 ± 1.6 NE per high‐power field). These findings support the hypothesis that IFN‐g modulates the inhibitory effects of Staphylococcal enterotoxins on NE functional properties.Support or Funding InformationCAPES‐Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (1676187).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Endothelin‐1 Induced Fibronectin Expression via c‐Jun
Authors: Hernandez Sergio J.r 
Published: June 2021

Glaucoma is an optic disease that is characterized by slow neurodegeneration of the optical nerves and steady loss of retinal ganglion cells. Over 70 million people suffer from glaucoma and it is estimated that over 118 million will suffer from it in 2040. A prime factor causing glaucoma is an increased in intraocular pressure (IOP) but the mechanism in how IOP contributes to glaucoma is still being studied. Blocking the aqueous humor through the trabecular meshwork (TM) is a major contributor for the IOP elevation. Endothelin (ET‐1) is a potent vasoconstrictor in which play's an important role in vascular system. Previous research has discovered that ET‐1 and its ETA/ETB receptors are also involved in the pathogenesis of glaucoma. The current study aims to test whether ET‐1 induced fibronectin deposition at TM. We hypothesize that ET‐1 induces over expression of fibronectin through c‐Jun‐mediated signaling pathway. Primary human TM cells were pretreated with c‐Jun siRNA, SP600125 (a JNK inhibitor to block activation of c‐Jun) or ET receptor antagonist's followed with ET‐1 treatment. Protein levels of fibronectin and c‐Jun were detected using immunoblotting. An increase of fibronectin and c‐Jun were detected in TM cells treated with ET‐1 for 24–72 hours. Fibronectin was increased as a result of c‐Jun being partially terminated by the knockdown of c‐Jun by C‐Jun siRNA. Blocking of ETA/ETB by BQ610/BQ788 reduced the expression of fibronectin. Our results preliminary demonstrate that ET‐1 induces the expression of fibronectin through c‐Jun mediated signaling pathway, suggesting that ET‐1 may cause the accumulation of fibronectin at TM contributing to IOP elevation.Support or Funding InformationThis work was supported by the Department of Health and Human Services, National Institute of Health, National Heart, Lung and Blood Institute, SMART Award Number 4R25HL007786‐25 to Harlan Jones, Ph.D This work was also supported by MARC U*STARGrant5T34GM008395 to MariaElena Zavala, Ph.DThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High‐precision and scalable fabrication of biomimetic culture environments for enhancing adherent mammalian cell and tissue engineering
Authors: Ghazizadeh Hamed , Fisher Elliot , Gray Kevin M , Geisse Nicholas A 
Published: June 2021

Cells maintained in vitro typically lose various structural and functional phenotypes that are found in vivo. Generation of biomimetic substrates typically involves costly or hard‐to‐reproduce techniques that are often incompatible with many standard assays. Here, we will present a novel method of generating surfaces that mimic the nanoscale shape and structure of the collagen ECM. The fabrication scheme described is highly reproducible, scalable, and amenable to integration with most end‐point assays, including high‐NA optical microscopy. Further, we present techniques to can fabricate biomimetic culture surfaces out of elastomers that can be stretched in order to reproduce mechanical stimuli that are critical in the development and function of some tissues. Various cell types were tested and were amenable to this approach. Cardiac tissues showed more in vivo‐like myofibril alignment, sarcomere spacing and width, and expression of CM‐specific proteins. Stem‐cell derived CMs similarly showed earlier onset of maturity and differentiation. We will show that the nanoscale patterning also maintains the migratory phenotype of metastatic cancer cells in vitro. Finally, we will demonstrate that this patterning approach can be extended to high‐throughput electrophysiological assays when combined with micro‐electrode arrays (MEAs) without compromising signal fidelity but enhancing sensitivities to drugs of known in vivo effect.Support or Funding InformationNIH SBIR FundingThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Age‐Related Changes in Skeletal Muscle and Small Mesenteric Arterial Function in Spontaneously Hypertensive Rats
Authors: Jurrissen Thomas Jacob , Castorena‐Gonzalez Jorge A , Ramirez‐Perez Francisco I , Hill Michael A , Meininger Gerald A , Padilla Jaume , Martinez‐Lemus Luis A 
Published: June 2021

Essential hypertension is a chronic idiopathic medical condition that is characterized by elevated arterial blood pressure and is associated with increased risk of cardiovascular disease. Endothelial dysfunction is associated with increased age and a casual factor for the development of hypertension. Therefore, we hypothesized that endothelial dysfunction would be exacerbated by age to a greater extent in spontaneously hypertensive rats (SHRs) compared to Wistar‐Kyoto rats (WKY) control rats. Vascular function was assessed using pressure myography in skeletal muscle and mesenteric resistance arteries isolated from SHR and WKY across three age groups: young (16–17 weeks, n = 4/group), aged (62–64 weeks, n = 4/group) and old (88–100 weeks, n = 5/group). Phenylephrine‐induced vasoconstriction responses in either of the resistance arteries were not significantly different between WKY and SHR at any of the age groups. Endothelial‐dependent vasodilation in mesenteric arteries was not significantly different between WKY and SHR across age groups either. However, endothelium‐dependent vasodilation in the skeletal muscle resistance arteries was significantly enhanced in the young SHR compared to WKY, but not in the aged or old rats. Moreover, endothelial‐independent vasodilation in mesenteric arteries was significantly enhanced in SHR compared to WKY across all age groups, while this difference was only observed in the skeletal muscle resistance arteries of the young rats. Contrary to our hypothesis, these data suggest that endothelial dysfunction is not exacerbated by age in the resistance arteries of SHR.Support or Funding InformationResearch support: National Institute of Health grants: R01 HL137769 (JP), R01 HL088105 (LM‐L).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Treatment of Hypertension with Stable Analogue of 14, 15‐Epoxyeicosatrienoic Acid (EET‐A) in Spontaneously Hypertensive Rats
Authors: Baranowska Iwona , Gawrys Olga , Walkowska Agnieszka , Husková Zuzana , Honetschlagerová Zuzana , Cervenka Ludek , Falck John , Kompanowska‐Jezierska Elzbieta 
Published: June 2021

IntroductionHypertension and concomitant complications, such as blood circulation disorders, stroke, heart attack or kidney failure, became one of the leading causes of death in the world. Recent reports indicate on epoxyeicosatrienoic acids (EETs) as significant factors in blood pressure regulation. These cytochrome P‐450 dependent metabolites of arachidonic acid, exhibit vasodilator and natriuretic activity. It has been shown that EETs facilitate the production of vasodilatory NO, protect the endothelium, exhibit antioxidant properties and might inhibit inflammation. All of the above‐mentioned features should contribute to the reduction of blood pressure and adverse effect of hypertension, hence we postulate the usefulness of EETs as novel drugs for the prevention and/or treatment of hypertension. In the present study the potential hypotensive efficiency of a stable analogue of 14,15‐EET: disodium (S)‐2‐(13‐(3‐entyl)ureido)‐tridec‐8(Z)‐enamido) succinate, called EET‐A, in genetic model of hypertension (spontaneously hypertensive rat, SHR) was evaluated.MethodsMale SHR (n = 6) in the established stage of hypertension (16 weeks) were treated for four weeks with EET‐A dissolved in drinking water (10 mg/kg/day); aged‐matched control group received water only (n = 6). Systolic blood pressure (SBP) was measured by telemetry technique every three days. Once a week observations in metabolic cages (food and water intake, feces, diuresis) were performed; urine and blood samples were collected for further analysis. Nitric oxide metabolites and vascular endothelial growth factor (VEGF) content in urine was measured with commercial ELISA kit.ResultsPreliminary results showed that EET‐A did not impact the blood pressure of adult SHR. We did not observe any changes in diuresis, water and food intake. Also sodium excretion did not change after EET‐A treatment, however, surprisingly, it significantly increased in the control group (EET‐A day 0: 0.5 ± 0.1 vs day 28: 0.5 ± 0.1, NS; control group day 0: 0.4 ± 0.2 vs day 28: 1.0 ± 0.1#* mmol/24h, *p<0.05 within the control group; # values on day 28th between groups, p<0.05). The excretion rates of NO metabolites (nitrates/nitrites; NOx) and VEGF‐A increased significantly in the EET‐A treated group (NOx day 0: 0.99 ± 0.18 vs day 28: 1.56 ± 0.13 μmol/24h, p<0.05; VEGF‐A day 0: 3.2 ± 0.7 vs day 28: 9.5 ± 2.0 ng/24h, p<0.05).SummaryAnalysis of the obtained data suggests that EET‐A in the applied dose does not lower blood pressure. Further studies are necessary to investigate if, despite the lack of blood pressure decrease, EET‐A improved kidney function.Support or Funding InformationNational Science Centre 2017/26/M/NZ5/00367This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Two‐Weeks of Remote Ischemic Preconditioning Alters Sympathovagal Balance
Authors: Gardner Richard N , Sabino‐Carvalho Jeann L , Vianna Lauro C , Lang James A 
Published: June 2021

Remote ischemic preconditioning (RIPC), elicited by brief, intermittent periods of ischemia followed by reperfusion, has cardioprotective effects. Our lab recently found that repeated bouts of RIPC improves microvascular function; however, it is unclear whether autonomic function would also be affected. We hypothesize that heart rate variability (HRV) will be altered following two weeks of repeated RIPC. Eleven healthy adults (age = 22 ± 2 yrs, 6 males, 5 females, BMI = 23.1 ± 3.4) performed two weeks of RIPC over 3 four‐day periods, each separated by a one‐day break. Each RIPC session consisted of 4 repetitions of 5 minutes of arm blood flow occlusion interspersed by 5 minutes of reperfusion. Before and one day after two weeks of RIPC, resting heart rate was collected with lead II electrocardiogram (ECG) while the participant was comfortably lying in a semi‐recumbent position in a quiet, dimly lit thermoneutral environment. Power spectral density and symbolic dynamics were used to assess HRV from ~350 beat ECG segments. Two weeks of repeated RIPC decreased the percentage of 0V beat fragments (pre‐RIPC = 13.1 ± 6.5%, post‐RIPC = 6.9 ± 4.9%, P < 0.05) and increased the percentage of 2V beat fragments (pre‐RIPC = 42.9 ± 12.1%, post‐RIPC = 52.5 ± 10.0%, P < 0.01), while decreasing the LF/HF ratio (pre‐RIPC = 1.1 ± 0.6, post‐RIPC = 0.7 ± 0.3, P < 0.01). Thus, both the spectral and fractal analyses indicate that repeated RIPC shifts sympathovagal balance by increasing parasympathetic and decreasing sympathetic activity.Support or Funding InformationFunded by the Iowa Space Grant ConsortiumThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Endothelial cell‐mediated formation of high density lipoprotein‐like particles
Authors: Yang Hong , Zhang Ningya , Okoro Emmanuel U. , Hairston‐Paschall Jenaqua , Guo Zhongmao 
Published: June 2021

Passage of plasma triglyceride‐rich lipoproteins (TRLs) and low‐density lipoproteins (LDLs) through the monolayer endothelium occurs in normal and atherosclerotic arteries. The current report studied the effect of transendothelial transport on the density distribution of TRL‐ and LDL‐associated cholesterol and apolipoproteins (apo). Our data indicated that the 3H‐cholesterol and 125I‐apoE in the TRLs and LDLs that were not incubated with the mouse aortic endothelial cell (MAEC) monolayer distributed primarily in the low density (LD) fractions (d: ≤1.063). In contrast, a substantial portion of the 3H‐cholesterol and 125I‐apoE that had passed through the MAEC monolayer were allotted into the high density (HD) (d: ≥1.063) fractions. ApoB protein was detectable only in the LD fractions before or after TRLs or LDLs were incubated with the MAEC monolayer. Inhibition of caveolae‐dependent endocytosis reduced the transendothelial transport of TRLs and LDLs and its associated apoE‐carrying HD particle formation. These suggest that TRLs and LDLs pass through the MAEC monolayer in the forms of apoB‐carrying LD particles and apoE‐carrying HD particles.Support or Funding InformationNIH SC1HL101431This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Study of a New Working Memory Paradigm for Hypertensive Patients
Authors: Paradela Regina , Cabella Brenno , Nucci Mariana Penteado , Irigoyen Maria Claudia 
Published: June 2021

Working memory (WM) has been extensively explored in the field of cognitive neuroscience, and several programs have been developed to train this ability in different clinical conditions. Among them, Cogmed stands out, since its effects have shown beneficial for many populations, but few studies have evaluated the effects of this training on brain function. In addition, none of these studies were with hypertensive patients who are known to have deficits in executive functions, including WM. Therefore, the aim of this study was to evaluate the neuronal activation of hypertensive patients during a WM task. A next step will be to re‐evaluate activation after training with Cogmed and compare it with pre‐training. The results described are related to the pilot study carried out to evaluate the feasibility and adequacy of the proposed protocol. The pilot study was composed by two stages: 1) stimulus programming in E‐prime software version 1.2; and 2) acquisition of structural and functional images on a 3.0 T magnetic resonance imaging device, followed by analysis of the activation of brain areas of interest. The paradigm was adapted from Brehmer et al., 2011 and consists of two active conditions with different levels of difficulty, Low (4 stimuli) and High (6 stimuli), and their respective controls. The sample consisted of 4 healthy young volunteers and 1 patient with hypertension, as an exploratory analysis for future study intervention. The activation map obtained corresponds to the group analysis of these volunteers and the term ‘activation’ refers to the positive BOLD contrast. In the group activation maps (n = 4 Z‐score> 2.3; p, <0.05), the most activated regions in Low were superior parietal lobe, precuneus, frontal lobe, medial frontal gyrus, pre‐central gyrus, cingulate gyrus, temporal lobe, fusiform gyrus and thalamus; in the High condition the most activated areas were superior parietal lobe, precuneus, insula, frontal lobe, medial frontal gyrus and thalamus; and in the comparison between the active conditions (High x Low), we observed higher activation in the High condition in the superior parietal lobe. These preliminary results showed that the paradigm is activating areas involved with WM processing and a statistically significant difference between the conditions tested. In this way, we considered the protocol adequate to evaluate the neuronal activation during a WM task in a larger group of volunteers (N = 40) with arterial hypertension.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CD8 T cells exert a critical role in the transition from left heart failure to lung remodeling and right ventricular hypertrophy
Authors: Wang Dongzhi , Weng Xinyu , Yue Wenhui , Chen Yingjie 
Published: June 2021

BackgroundPatients with left ventricular (LV) failure or heart failure (HF) often progress to right ventricular (RV) hypertrophy and/or failure even with optimal medical care. Previously, we have shown a potential role for regulatory T cells (Tregs) in suppressing LV failure progression. However, the particular leukocyte subset(s) that promote the transition from LV failure to RV hypertrophy and failure are unknown. Here, we investigated the role of cytotoxic CD8+T cells in this progression.MethodsMice with LV failure produced by transverse aortic constriction (TAC) were randomized to depletion of cytotoxic CD8+T cells using specific blocking antibodies. The cardiac function, lung inflammation, fibrosis, vascular remodeling, and right ventricular remodeling were determined.ResultsLV failure caused lung inflammation and lung T cell activation involving both CD4+and CD8+T cell activation. Depletion of CD8+ T cells dramatically attenuated the increase of lung weight, lung inflammation, lung vascular remodeling, and RV hypertrophy in mice with existing LV failure.ConclusionsOur findings demonstrate that CD8+T cells play a critical role in promoting the transition from LV failure to lung remodeling and RV hypertrophy, indicating that modulation of CD8+T cell activity may represent a new approach to heart failure therapy.Support or Funding InformationThis study was supported by research grants 81470512 and 81570355 from Nature Science Foundation, and Grants HL098669, HL102597, R01HL105406 from the National Institutes of Health, and a grant in aid from American Heart Association.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.