bluuebunny/crossref_metadata_2025_split huggingface dataset:
AVP‐ANP Signaling Axis in Salt‐Sensitive Hypertension
Authors: Polina Iuliia , Kurashkina Elizaveta , Sultanova Regina , Domondon Mark , Bankir Lise , Staruschenko Alexander , Ilatovskaya Daria 
Published: June 2021

High salt (HS) diet in salt‐sensitive (SS) individuals leads to development of hypertension and associated renal complications. Atrial natriuretic peptide (ANP) is proposed to attenuate SS hypertension by improving sodium and water excretion, thus lowering blood pressure (BP). Intriguingly, both the ANP receptor and the vasopressin‐dependent urea transporter UT‐A1 are abundantly expressed in the terminal collecting duct (CD). This segment is a major site of urea reabsorption and accumulation, and a key player in the urine concentrating mechanism. We hypothesized that ANP and vasopressin (AVP) may exert coordinated effects on salt, urea and water transport in the terminal inner medullary CD. To test this hypothesis, we compared wild type (WT) Dahl Salt Sensitive (SSWT) rats to SS rats lacking the Nppa gene which encodes for ANP (SSNppa−/−). The rats were fed either a high salt (HS, 4% NaCl) or a low salt (LS, 0.4% NaCl) diet for 21 days (Dyets, Inc). BP was monitored throughout the study using telemetry, and 24 hour urine samples were collected in metabolic cages on days 0 and 21 of the salt challenge. At the end of the protocol, rats were euthanized, kidneys and plasma samples were harvested.SSNppa−/− rats fed a HS diet exhibited severely elevated BP and attenuated diuresis (11.3 ± 0.7 vs 3.9 ± 0.9 mL per day) compared to SSWT controls. Urinary osmoles excretion was reduced SSNppa−/− rats on a HS diet. ELISA assay revealed that 24h urea excretion was significantly lower in SSNppa−/− rats on HS diet (87 ± 12 vs 139 ± 8 mg per 100 g of body weight in SSWT; p=0.003). These data suggest that SSNppa−/− rats have lower urine concentrating ability on HS diet compared to SSWT. Expression of AVP receptors (AVP2R) in the renal tissue was significantly reduced in SSNppa−/− on both diets compared to SSWT controls as shown by Western blot analysis, and further confirmed in immunohistochemical staining for both cortical and medullary CDs. However, we did not find statistically significant difference in urinary copeptin level (used as a surrogate marker for AVP) between SSWT and SSNppa−/− rats on LS diet (10.0 ± 2.8 pg/mL; vs 8.9 ± 0.8 pg/mL, respectively). CDs of SSNppa−/− rats fed a HS diet demonstrated a dramatically increased expression of AQP2 channels compared to SSWT, which did not differ in LS‐diet fed groups. Understanding ANP/AVP signaling axis and interaction with respect to water and sodium transport in the CDs can help us find new targets for medications to best compromise between efficient natriuresis and urine concentrating ability.Support or Funding InformationSupported by NIH.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Salt Loading Effects on ENaC and Blood Pressure in Aged 129Sv Mice
Authors: Schramm Whitney C. , Malik Zeeshan S. , Liu Lauren P. , Chacko Kevin M. , Alli Abdel A. 
Published: June 2021

Essential hypertension in the elderly population is a major public health problem because these patients usually do not respond well to antihypertensive drugs. More than half the cases of essential hypertension are thought to be associated with salt sensitivity from excessive dietary salt intake. We hypothesized that salt loading augments renal epithelial sodium channel expression and blood pressure in aged 129Sv mice. The renal epithelial sodium channel regulates total body salt balance and blood pressure, but mechanisms for its regulation by dietary salt intake in the aged kidney are not completely known. Twelve month old 129Sv mice were subject to salt loading for 4 weeks. Water intake, urine production, blood pressure, and electrolytes in the urine were measured before and after salt loading. Both the total and cleaved forms of ENaC subunits were assessed by Western blotting and densitometric analysis. ENaC alpha protein was augmented in the kidneys of salt‐loaded hypertensive 129Sv mice compared to non‐salt loaded mice. Water intake, urine output, and systolic blood pressure significantly increased in the 129Sv mice after salt‐loading. Salt loading resulted in an increase in urinary sodium levels and a decrease in urinary potassium levels. These findings may provide new links between salt‐sensitivity, ENaC expression, and blood pressure regulation in the aged kidney.Support or Funding InformationThis project was funded by the U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (Grant K01 DK099617; to A.A.A.) and the University of Florida College of Medicine.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 effectiveness of flaxseed (Linum usitatissimum L.) on the inflammatory response in patients with familial hypercholesterolemia receiving lipid apheresis‐preliminary results
Authors: Kanikowska Dominika , Rutkowski Rafał , Pawlaczyk Krzysztof , Sato Maki , Misian Monika , Bręborowicz Andrzej , Witowski Janusz 
Published: June 2021

Familial hypercholesterolemia is associated with severe abnormalities including atherosclerosis, dyslipidemia, cardiovascular disease, oxidative stress, inflammation, and endothelium dysfunction. Flaxseed in the diet acts upon blood lipids, lowering cholesterol, and also has anti‐oxidative effects. These effects are beneficial for patients suffering from atherosclerosis, dyslipidemia and endothelium dysfunction.The protocol consists of four stages: a run‐in phase of 10 weeks (patients on a standard diet) and an experimental stage ‐ flaxseed supplementation or placebo (whole‐wheat) supplementation, and wash out phase of 10 weeks. Samples of saliva and blood were collected after each phase of the trial, just before routine lipoprotein apheresis, which is usually once every two weeks. Saliva myeloperoxidase levels were analyzed by ELISA test, and flow cytometry was used for measurement of circulating microparticles. The study adhered to the Principles of the Declaration of Helsinki.The concentration of salivary myeloperoxidase was lower after flaxseed supplementation.The number of circulating microparticles: CD105 (endothelial‐derived), CD45 and CD41 (platelet‐derived)) was smaller after flaxseed supplementation compared with a run in phaseConclusionsOur preliminary observations indicate that a diet containing flaxseed may improve endothelial cell function and thus contribute to the amelioration of unfavorable effects associated with hypercholesterolemia.Support or Funding InformationThere is no actual or potential conflict of interest in this presentation. The Nutricia Research Foundation Poland provided the research grant support.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Predicting Protein Glycation Rate and State: The Need for Models to Incorporate Additional Features
Authors: Turkette Thomas , Rhinesmith Tyler , Root‐Bernstein Robert 
Published: June 2021

Glucotoxicity is considered to be one of the primary drivers in type 2 diabetic (T2D) pathophysiology. As such, understanding the mechanisms underlying glucotoxicity is imperative in the identification, treatment, and prevention of T2D. One contributor to glucotoxicity is protein glycation in which a reducing sugar spontaneously reacts with the ɛ‐amino group of lysine residues or an N‐terminal amino group to form a covalently bound adduct. Here we test two methods employed to predict whether a given protein sequence will undergo glycation and whether either method offers insight toward predicting the rate of glycation in vitro. The first method involves looking for sequences that are homologous to known glucose binding regions, while the second utilizes NetGlycate‐ a neural network trained to predict glycation based on a protein sequence. Both methods were used to predict potential glycation sites on the human insulin receptor and regions containing these sites were synthesized. These fragments were then incubated in high glucose for 1, 3, or 6 days. The extent of glycation was assessed using MALDI‐ToF mass spectrometry. There was some overlap in the residues predicted to undergo glycation, but both methods also predicted unique sites. Both methods generated a number of false positives, but sites predicted by both methods were generally more likely to undergo glycation. Additionally, several of the sites predicted that were unique to one method underwent glycation. The rate of glycation for a given site varies greatly regardless of the method employed to predict it and this holds true even when both methods predicted the same site. Our results suggest: 1) neither method is sufficient to independently predict protein glycation consistently and accurately, 2) a model that incorporates both evolutionary considerations in addition to protein sequence would be expected to better predict protein glycation, and 3) neither approach informs the rate of protein glycation, suggesting that some other factor(s) must also be at play.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A New Player in Intra‐islet Communication: The Hyperglycemic Effects of Neuronostatin through Increased Glucagon Production and Reduced Insulin Release
Authors: Grote Stephen , Yosten Gina , Samson Willis 
Published: June 2021

The tight regulation of blood glucose with insulin and antidiabetic agents greatly increases the risk and dangers of hypoglycemia in patients with Type 1 and Type 2 Diabetes. In addition, repeated bouts of hypoglycemia diminish the sympathetic arms of the counterregulatory response and blunt awareness of symptoms, creating a vicious cycle of unawareness and increasingly severe hypoglycemia. The only option in preventing or reversing hypoglycemia unawareness is careful avoidance of hypoglycemia through close monitoring– an often unobtainable goal. There is great need for other therapies and better understanding of diabetic hypoglycemia. We recently identified a novel peptide, neuronostatin (NST), encoded in the somatostatin preprohormone and found in all somatostatin‐positive tissues and cells. However, the activity of NST is functionally distinct from other preprosomatostatin products. Furthermore, it appears the physiologic stimuli of the peptides are different and that the peptides are sequestered in separate secretory vesicles. Our group identified the orphan GPCR, GPR107, as a cognate receptor of NST. Through an interaction with GPR107, NST enhanced proglucagon mRNA expression and glucagon release from isolated islets and immortalized alpha cells. NST also reduced beta cell release of insulin in response to high glucose conditions in isolated islets. Based off our findings, we hypothesized that NST is a pancreatic component of the counterregulatory response to hypoglycemia. In support of our hypothesis, an infusion of NST substantially increased plasma glucose levels over a 30‐minute time period in male rats. Additionally, NST delayed glucose clearance and diminished the insulin response to hyperglycemia in a glucose tolerance test. Fasting blood glucose raised plasma NST levels in rats, and exposure to low glucose stimulated NST release from human islets. Further experiments will confirm the role of NST in preventing or reversing hypoglycemia and determine how NST plays a role in the complex relationships of islet regulation and signaling. We propose that NST could represent a novel therapeutic target for the treatment and prevention of hypoglycemia in diabetes.Support or Funding InformationThis work was completed with funding support from the NIH and NIDDK, and the Helmsley Charitable Trust.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Constructing glucagon biosensors as an alternative to conventional detection methods
Authors: Ennis Teresa Annmarie , Samson Willis K. , Yosten Gina L. C. 
Published: June 2021

Glucagon is a counterregulatory hormone, produced by the pancreatic alpha cells, that is essential for protection against hypoglycemia. In patients with Type 1 Diabetes, failure of appropriate glucagon responses can lead to severe hypoglycemia, coma, and death. Studies into the regulation of glucagon secretion have been hindered by a lack of assays that exhibit adequate specificity and sensitivity. To overcome this limitation, we constructed glucagon biosensors expressing the glucagon receptor and the calcium sensor, GCamP6s. First, HEK‐293 cells were transfected with a GCGR (RFP‐Tagged) Human Glucagon Receptor vector, followed by transfection with the GCamP6s calcium reporter (GFP). After transfection, the cells were then passaged and maintained with media containing puromycin and G418 to isolate the cells that took up both vectors. Expression of the vectors could then be detected and monitored for changes stimulated by glucagon under different glucose conditions. After applying varied concentrations of glucagon, the GFP signal was detected using microscopy. The images produced clearly showed the receptor was visible in the membrane, and when glucagon was present the GCamP6s sensor was activated. In future studies, these glucagon‐sensing cells can be utilized to detect and monitor glucagon release from isolated islets, offering an alternative to conventional detection methods such as ELISA.Support or Funding InformationNIHThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lactobacilli ‐induced Generation of Reactive Oxygen Species via Formyl Peptide Receptor‐1 (FPR1) Regulates Intestinal Motility in Mice
Authors: Chandrasekharan Bindu , Saeedi Bejan , Alam M Ashfaqul , Srinivasan Shanthi , Tansey Malu , Jones Rheinallt , Nusrat Asma , Neish Andrew S 
Published: June 2021

RationaleVarious clinical conditions like diabetes and inflammatory diseases of the gut are associated with gastrointestinal (GI) motility disorders. Despite the increased consumption of beneficial commensal microbes marketed as ‘probiotics’, their mechanism of action on the enteric nervous system (ENS) is still unclear.AimWe studied the effects of the widely used probiotic and normal commensal Lactobacillus rhamnosus GG (LGG) on ENS and GI motility.MethodsConventional (Conv), formyl peptide receptor‐1 (FPR1 KO) and formyl peptide receptor‐2 (FPR2 KO) knockout mice were gavaged with hanks buffered salt solution (HBSS, negative control) or LGG. Mice were sacrificed after 2 h, and the jejunum was cryofixed and immunostained for phospho‐Erk (p44/42 MAPK, mitogen activated protein kinase). In a separate experiment, mice were intra peritoneally injected with a fluorescent hydro‐cy3 dye prior to HBSS/LGG gavage, and production of reactive oxygen species (ROS) was assessed in the longitudinal muscle myenteric plexus (LMMP) by confocal imaging after 2h. Ileum was assayed for gene expression of neuropeptides and Hand‐2 (transcription factor promoting enteric neuronal differentiation) by real time polymerase chain reaction (qRT‐PCR). Fluorescence in situ hybridization (FISH) was done on ileal cryosections from conventional mice using FPR1 and peripherin (pan neuronal marker) RNA probes. Conv mice were gavaged daily with HBSS or LGG for 2 weeks, and motility was assessed from stool frequency, total gastrointestinal transit time and ex vivo studies on isolated circular muscle strips by isometric muscle recording.ResultsLGG stimulated myenteric ROS production, enhanced Erk 1/2 phosphorylation and upregulated choline acetyl transferase (ChAT) neurons (P < 0.001) in Conv and FPR2 KO mice. These effects were abrogated in FPR1 KO mice, suggesting that LGG‐mediated signaling in the ENS is redox‐dependent and requires FPR1(P < 0.001), localized on enteric neurons by FISH assay. Functionally, LGG gavage for 2 weeks significantly improved stool frequency, reduced total GI transit time and enhanced ileal circular muscle strip contractions (P < 0.05).ConclusionsOur study demonstrates for the first time, the presence of FPR1 on enteric neurons, and the LGG‐FPR1‐dependent redox‐signaling pathway that could be exploited to improve GI motility.Support or Funding InformationWe acknowledge support from the U.S. National Institutes of Health grant AI64462 (A.S.N.) and DK089763 (A.N. and A.S.N.)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Chrysin on intestinal inflammation and gut microbiota in lipopolysaccharides‐induced mice
Authors: Wu Wen‐Tzu , Wang Zhi‐Hong 
Published: June 2021

Chrysin is a natural flavonoid with a variety of biological activities such as antioxidant, antivirus, antitumor, antidiabetic and so on. However, the potential protective effects of chrysin, against lipopolysaccharides (LPS)‐induced intestinal inflammation and its associated alteration of gut microbiota have not been studied. In the present study, male C57BL6/J mice were randomly divided into three groups and fed either normal chow diet (CON and LPS groups) or that supplemented with 1% (wt/wt) chrysin (CHY group) for 28 days followed by a single intraperitoneal injection of LPS (10 mg/kg BW). Control mice were given normal saline and all animals were kept for 72 hours before sacrifice. The results showed that chrysin attenuated histological injury of intestine and the production of pro‐inflammatory cytokines, TNFα, IL‐6 and IL‐1β. When compared to the LPS group revealed at genus level, CHY increased the proportion of Alloprevotella and Lachnospiraceae NK4A136, and decreased Escherichia_Shigella and Akkermansia. Furthermore, LPS group showed lower species richness of gut microbiota compared to the control animals, and the reduction was reversed by the addition of chrysin. In conclusion, chrysin can attenuate the LPS‐induced intestinal damage in mice. This protective effect appears to be mediated, in part, through beneficial changes to the microbiota.Support or Funding InformationThis study was supported by the National Science Council Grant 105‐2320‐B‐468‐001 Taipei, Taiwan.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Posttreatment Thymoquinone Can Reverse High‐Dose, Atorvastatin‐Induced Renal Injury in Rats
Authors: Hassan Sherif Sabry , Youakim Magdy Fouad , Aboulhoda Basma Emad 
Published: June 2021

BackgroundAtorvastatin (ATO) is an HMG‐CoA reductase inhibitor used to lower blood cholesterol, but it causes renal injury in high doses, including the kidney. The active ingredient of Nigella sativa, Thymoquinone (TQ), has antioxidant, antiapoptotic, and antiinflammatory properties.Aim of studyThe aim was to investigate whether posttreatment TQ could reverse ATO‐induced renal injury, and the possible mechanism of action by which TQ produces such effect.MethodsForty adult male Sprague Dawley rats were divided into 4 groups: control, TQ‐treated, ATO‐treated, and combined ATO/TQ‐treated. Rats were euthanized by cervical dislocation. Blood samples and kidneys were tested for kidney functions, oxidative stress, and apoptosis markers and for histopathological examination. Data was expressed as mean ± standard deviation (SD) and categorical variables are presented as percentage. One‐way analysis of variance (ANOVA) and post hoc tests (Bonferroni test) were used for the comparison of mean values between groups. P values of less than 0.01 were assumed to be significant (P<0.01). Data analysis was done using Study data were analyzed using SPSS.ResultsThe ATO‐treated group showed an increase in kidney functions, decreases in the oxidative stress markers, reduced glutathione and catalase, and increases in the protein carbonylation, lipid peroxidation, and caspase 3 activity. The ATO/TQ‐treated group appeared to improve these pathological changes. Morphometric analyses of the histopathological and ultrastructural examination supported these results.ConclusionPosttreatment TQ seemed to ameliorate oxidative stress‐induced renal injury produced by high‐dose ATO, suggesting a potential clinical application to the administration of high‐dose ATO, in patients with renal insufficiency.Support or Funding InformationSelf‐FundedThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Visualizing Cellular Adaptations during Ozone‐induced Lung Inflammation
Authors: Aulakh Gurpreet K , Singh Jaswant , Snead Elizabeth 
Published: June 2021

Ozone (O3) is a prevalent environmental pollutant with well‐documented acute and chronic health effects. Neutrophils are known as the prime orchestrators of lung immune surveillance. Although bacterial infections are known to elicit a robust lung neutrophil and alveolar macrophage response, it is not known why and how neutrophils are activated in response to sterile lung injury. Acute exposures to 2 ppm O3 induce lung macrophage and neutrophil extravasation and airway hyper‐reactivity at 24 h, however, these concentrations are manifold higher than ambient O3 concentrations, thus precluding any understanding of the initial events. Our pilot experiments established ozone's dose and time dependent killing of alveolar macrophages and concomitant recruitment of leukocytes. Our data indicated that 50 ppb of O3 induces cell death in half of the lung alveolar macrophage population. Thereafter, we exposed C57BL6 mice to either filtered air or 50 ppb of O3 for 2 h to understand the kinetics of murine ozone induced acute lung injury. We report acute vascular neutrophil concentration and activation at as early as 2 h post exposure which continues up to 24 h after ozone exposure. Immunofluorescent staining revealed CD11b positive lung alveolar macrophage and neutrophil recruitment. In addition to conventional bronchoalveolar lavage, lung vascular perfusate and peripheral blood analysis, we present novel application of simple, yet powerful, configuration of a fixed‐stage wide‐field upright fluorescent intravital microscopic set‐up to investigate ozone's oxidative lung damage. We observed extensive alveolar actin filament disorganization (Fig. 1), an initial drop (at 2 h post‐O3 exposure) followed by restoration (18 h post‐O3 exposure) of alveolar reactive oxygen species (ROS) (Fig. 2) as well as mitochondrial potential (Fig. 3) in live animals. Important findings from these preliminary experiments include CD11b predominant phenotypes of pulmonary leukocytes, alveolar necrosis, actin disorganization, acute alterations in alveolar ROS production as well as mitochondrial potential. Thus, we present evidence of systemic as well as lung toxicity at 40 fold lower O3 concentrations. The findings are important in establishing a sensitive model of ozone induced acute lung injury.Support or Funding InformationFedoruk Centre and Innovation Saskatchewan.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.