bluuebunny/crossref_metadata_2025_split huggingface dataset:
EVALUATION OF MINERAL BONE DISEASE IN PATIENTS WITH ACUTE KIDNEY INJURY
Authors: Morales Armando , Lanzoni Luís Gustavo , Silveira Cylmara Gargalak Aziz , Grabulosa Caren Cristina , Pinto Walter Pereira , Tinucci Taís , Moysés Rosa Maria Affonso , Quinto Beata Marie Redublo , Batista Marcelo Costa , Dalboni Maria Aparecida 
Published: June 2021

IntroductionPatients with end‐stage renal disease (ESRD) develop various kinds of abnormalities in bone and mineral metabolism, widely known mineral bone disease (MBD). The MBD is one of the main cause of vascular calcification (VC) and mortality in this patients. This abnormalities are a consequence of the glomerular filtration rate declined and retention of a large number of compounds which under normal conditions are excreted by healthy kidneys. In the last years, Fibroblast Growth Factor 23 (FGF‐23) a phosphaturic hormone, Sclerostin (SOST) (a protein that inhibit bone formation ) and inflammation markers have been described as a important axis of the physiopathology of MBD and VC in ESRD. The early detection of MBD can reduced the VC and its complications. However, patients with acute kidney injury (AKI) which abruptly lose kidney function; have not been yet investigated to MBD. Thus, the objective of this study was to investigate markers of MBD in AKI patients.Material and MethodsWe included 77 severe patients without AKI and 83 severe AKI patients (ageing‐ 77 (60–84) all admitted to the Intensive Care Unit. Patients with AKI were characterized by AKIN criteria that used a 0.3 mg/dL increase in serum creatinine within seven days of admission in the hospital. Serum markers of MBD and inflammation investigated were: FGF‐23, SOST, Interleukin‐6 (IL‐6), Tumor Necrosis Factor Alpha (TNF‐α) and Interleukin‐10 (IL‐10) (by enzyme‐linked immunosorbent assay (ELISA). Results are expressed as median. Mann‐Whitney test was used to analyze the groups.ResultsAll AKI patients presented serum creatinine >3.1 mg/dL (reference value 0.8 – 1.3 mg/dL). We observed increased serum levels of SOST (pg/mL) [AKI 1.74 (1.74–46.40) vs. No‐AKI 1.74 (1.74–1.74); p=0.009)], IL‐6 (pg/mL) [AKI 21 (11–32) vs. No‐AKI 12 (7–19); p<0.001], TNF‐α (pg/mL) [AKI 8.2 (6.7–10.5) vs. No‐AKI 7.0 (6.2–7.9); p<0.001], IL‐10 (pg/mL) [AKI 1.1 (0.8–1.6) vs. No‐AKI 0.8 (0.7–1.0); p<0.001]. We did not observe difference in FGF‐23 (pg/mL) [AKI 48.3 (1.5–141.3) vs. No‐AKI 48.0 (1.5–188.5); p=0.35].ConclusionAKI patients presented higher inflammation state characterized by increased serum levels of IL‐6, TNF‐α and IL‐10. Additionally, as SOST was higher in AKI patients, is possible used it as a marker of early bone disease in this population. In summary, this is the first study that detected high levels of SOST in AKI patients.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cepharanthine improves glycemic status and slows the progression of renal and vascular injury in streptozotocin‐induced diabetic rats
Authors: Samra Yara A. , Katary Mohamed A. , El‐Shishtawy Mamdouh M. , Essa Laila A. , Baban Babak , Elmarakby Ahmed A. 
Published: June 2021

We have previously demonstrated that Cepharanthine improves glycemic status and reduces renal injury in streptozotocin‐induced diabetic rats via antioxidant and anti‐inflammatory mechanisms. However, the hypoglycemic mechanism of Cepharanthine remains unclear. We hypothesize that Cepharanthine reduces blood glucose in steptozotocin‐induced diabetic rats via restoring pancreatic β‐cells mass and insulin secretion. Diabetes was induced by a single i.p. injection of streptozotocin (50 mg/kg) in male Sprague Dawley rats. Control and diabetic rats were treated with Cepharanthine (10 mg/kg/day, i.p.) for six weeks (n=6–8). Cepharanthine treatment significantly reduced blood glucose levels and increased plasma insulin levels in diabetic rats (blood glucose was 290± 67 in Cepharanthine treated diabetic rats vs. 550±17 mg/dl in non‐treated diabetic rats, P<0.05). The percentage of TUNEL positive cells was significantly elevated in the pancreas of diabetic rats and these changes was reduced by Cepharanthine treatment (P<0.05). Immunohistochemcial analysis revealed a decrease in pancreatic islet‐specific glucose‐6‐phosphatase catalytic subunit related protein (IGRP) and an increase in pancreatic and duodenal homeobox 1 (PDX‐1) expression levels in Cepharanthine treated vs. non treated diabetic rats (P<0.05). Cepharanthine also improved vascular endothelial function as it significantly attenuated the impairment in aortic ring relaxation to acetylcholine in diabetic rats. Moreover, Cepharanthine reduced markers of renal injury and inflammation and slowed the progression of renal fibrosis as evidenced by the reduction in levels of albuminuria, podocalyxin excretion, renal ICAM‐1 and TGF‐β in diabetic rats. The reduction in renal inflammation and injury was associated with decreased in renal caspase 3 expression in Cepharanthine treated diabetic rats. These data suggest that Cepharanthine halts the progression of streptozotocin‐induced diabetic complications in rats via reduced pancreatic β‐cells apoptosis and increased β‐cells maturation and subsequently insulin release probably via the regulation of the PDX‐1 and IGRP transcription factors of pancreatic β‐cells.Support or Funding InformationThe work was supported by bridge funding grant from Augusta University, Augusta, Georgia to Dr. Ahmed A. ElmarakbyThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dietary Nitrate Enhances Peak Power in Aged Murine Diaphragm
Authors: Kelley Rachel C. , Kumar Ravi A. , Hahn Dongwoo , Ferreira Leonardo F. 
Published: June 2021

Inspiratory muscle (diaphragm) function declines with age. Aging‐related diaphragm atrophy and/or dysfunction likely contribute to impaired airway clearance and exercise intolerance in the elderly. The goal of our current study was to determine the therapeutic potential of dietary nitrate supplementation in aged diaphragm. Aging decreases the availability of nitric oxide (NO), but supplementation with NO precursors (e.g., sodium nitrate, beetroot juice, arginine) may augment NO production. Previous studies have shown that dietary nitrate may improve skeletal muscle contractile efficiency, mitochondrial function, and anabolism by enhancing NO's vasodilatory and/or cell signaling effects. In this study, old (n=14, 24 months old) mice received sodium nitrate (NaNO3, 1 mM) in drinking water or vehicle (deionized H2O) ad libitum for a total of 14 days. After treatment, diaphragm function was evaluated using isolated muscle bundles. Dietary nitrate supplementation did not result in improvements in maximal isometric force (control: 20.5 ± 2.9 vs NaNO3: 22 ± 3.4 N/cm2), twitch force (control: 3 ± 0.5 vs NaNO3: 3.6 ± 0.6 N/cm2), time‐to‐peak tension (control: 16.7 ± 0.5 vs NaNO3: 15.3 ± 1.7 ms), ½ relaxation time (control: 14.1 ± 1.8 vs NaNO3: 14.3 ± 2 ms), or maximal shortening velocity (control: 7 ± 3.1 vs NaNO3: 8.1 ± 1.2 Lo/s). However, dietary nitrate supplementation did significantly increase peak power from 161.4 ± 32.3 W/kg in controls to 224.8 ± 35.5 W/kg in supplemented mice (p < 0.05). Ventilation during exercise as well as non‐ventilatory behaviors needed for airway clearance, such as coughing and sneezing, require rapid, forceful contractions of the diaphragm. Therefore, our results suggest that supplementation with dietary nitrate may increase peak power and thus be of benefit in aging populations.Support or Funding InformationNIA 1R03AG04040001A1This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Electric stimulation alters intercellular stress within the epithelial monolayer
Authors: Cho Youngbin , Son Minjeong , Ko Ung Hyun , Jeong Hyuntae , Shin Jennifer Hyunjong 
Published: June 2021

IntroductionThe directed migration of cell plays a pivotal role in physiological processes such as development, wound healing, vasculogenesis, and cancer metastasis. Electric field (EF) is one of the prevailing guidance cues in vivo, which promotes directional migration in both single and collective cells. Numerous studies have studied the detailed biochemical mechanism of electrotaxis, directional guidance by EF, both in vivo and in vitro. However, these studies mainly focused on a single cell behavior. Since the collective cells are feeling severe confinement due to their neighboring cells, not only biochemical but also physical analysis is essential to understand the mechanism of coordinated cellular guidance by EF. Here, we aimed to investigate how the cellular physical forces are altered in response to externally applied direct current electric field (dcEF). We established the EF stimulating platform combined with polyacrylamide gel for the simultaneous measurement of Traction Force Microscopy (TFM) and Monolayer Stress Microscopy (MSM).Materials and MethodsIn this study, we developed cell observable platform, equipped with agar bridge and steinberg's solution to apply dcEF. To analyze cellular forces, we combined 0.5 μm fluorescence bead embedded poly‐acrylamide hydrogel within the chamber. We micropatterned HacaT cell‐line using PDMS stencil on the poly‐acrylamide gel before stimulating dcEF. After 1 day maturation of HacaT monolayer, we stimulated 0.5 V/cm dcEF continuously over the experiment. Traction field was calculated from the measured displacement field of fluorescent beads embedded within a hydrogel of 3 kPa stiffness. Gel displacement was quantified at each experimental time point, and a reference image was obtained after cell detachment. Traction was obtained by the numerical procedure from Fourier‐transform‐traction‐microscopy (FTTM). Based on the traction field, we calculated intercellular stress using monolayer stress microscopy (MSM).Results and discussionWe observed that the EF stimulation induced the rapid response of collective migration toward the anode. This guided migration was followed by the reorientation of individual cells to perpendicular axis against the EF direction. Interestingly, enhancement of intercellular stress component perpendicular to the EF preceded the coordinated alignment of cellular orientation within the epithelial monolayer. These results suggest that the EF‐induced formation of anisotropic intercellular stress leads the reorientation of individual epithelial cells within the bulk of collective monolayer.Support or Funding InformationThis work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF‐2013S1A2A2035518, NRF‐2016K2A9A2A08003761)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inclusion of Dairy Cheese In An 8‐day Controlled Dietary Intervention Prevents Sodium‐Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy Older Adults
Authors: Alba Billie K. , Stanhewicz Anna E. , Bruno Richard S. , Kenney W. Larry , Alexander Lacy M. 
Published: June 2021

Excess dietary sodium is associated with impaired vascular function and increased cardiovascular mortality. In controlled feeding studies, the inclusion of 3 daily servings of any dairy product improves blood pressure and measures of vascular health. Few studies have examined the inclusion of individual dairy products that contain both the beneficial bioactive dairy proteins and sodium. We recently demonstrated that single‐meal cheese consumption ameliorates acute sodium‐induced impairments in nitric oxide‐dependent vasodilation. However, controlled feeding studies examining the vasoprotective role of dairy cheese on sodium‐induced microvascular dysfunction are lacking. We hypothesized that (1) endothelium‐dependent vasodilation would be impaired by a high‐sodium diet compared to a low sodium diet, and (2) that a high‐cheese diet would preserve endothelium‐dependent vasodilation that is otherwise impaired by a high‐sodium diet. In a randomized, crossover study design, seven healthy older adults (63 ± 3 years; salt‐resistant: <10 mmHg increase in mean arterial pressure, 24 hour monitoring) with normal to elevated blood pressure completed 4 separate 8‐day controlled dietary interventions: 1) low‐sodium (LNa: 1500 mg sodium) diet devoid of dairy products, 2) low‐sodium high‐cheese diet (LNaC: 1500 mg sodium, 6 oz/d cheese), 3) high‐sodium (HNa: 5500 mg sodium) diet devoid of dairy products, and 4) high‐sodium high‐cheese diet (HNaC: 5500 mg sodium, 6 oz/d cheese). At the end of each dietary intervention, subjects participated in an intradermal microdialysis protocol in which one microdialysis fiber was inserted into the forearm skin for measurement of red cell flux (laser Doppler flowmetry) during local infusion of the endothelium‐dependent agonist acetylcholine (Ach; 10−12 to 10−1 M). Data were expressed as a percentage of maximum cutaneous vascular conductance (%CVCmax; 28 mM sodium nitroprusside, 43°C). Ach‐induced vasodilation was significantly attenuated during the HNa diet compared to the LNa diet (LNa: −5.06±0.20 M vs HNa: −3.22±0.63 M logEC50: p < 0.05). Conversely, Ach‐induced dilation during either the LNaC or HNaC diet was not different from the LNa diet (p > 0.05). These results demonstrate that increased dietary sodium intake impairs endothelium‐dependent dilation whereas the inclusion of cheese prevents sodium‐induced endothelial dysfunction in salt‐insensitive older adults.Support or Funding InformationSupported by National Dairy CouncilThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regulation of basolateral ClC‐K2‐dependent Cl‐ reabsorption in collecting duct intercalated cells by dietary electrolyte intake and Ang II
Authors: Zaika Oleg , Tomilin Viktor N. , Pochynyuk Oleh M. 
Published: June 2021

Hypertension is the major clinically relevant problem, which commonly stems from excessive renal salt retention. Both basic and clinical studies show that elevated dietary Na+ can promote volume expansion and increased blood pressure only when accompanied with high Cl−. The collecting duct (CD) is the only tubular segment with capacity to separately reabsorb Na+ and Cl−. Here, principal cells perform electrogenic Na+ reabsorption via the epithelial Na+ channel (ENaC), whereas activity of the basolateral ClC‐K2 chloride channel mediates trans‐cellular Clmovement in electrically uncoupled intercalated cells. In contrast to ENaC, little is known about dietary and hormonal means controlling ClC‐K2 activity in the CD. Using patch clamp electrophysiology at both single channel and macroscopic levels in freshly isolated CDs, we found that ClC‐K2 single channel activity and macroscopic Cl− conductance in intercalated cells are inversely related to dietary Cl−, but not K+ intake. Furthermore, stimulation of mineralocorticoid receptors with deoxycorticosterone acetate (DOCA) failed to affect ClC‐K2 activity arguing against a role of aldosterone in regulation of ClC‐K2 by dietary Cl−. In contrast, Angiotensin II (Ang II) exerts a set of stimulatory actions by acutely increasing ClC‐K2 single channel open probability, ClC‐K2/b‐dependent Cl− conductance in ICs and on a longer timescale promotes ClC‐K2/b trafficking to the basolateral membrane of ICs in freshly isolated CDs implicating its potential role during variations in dietary Cl− intake. Inhibition of AT1 receptors (AT1R) with losartan precluded regulation of ClC‐K2 by Ang II. Moreover, ClC‐K2 abundance was significantly reduced in mice lacking AT1R. Overall, our results point to a critical role of dietary Cl− in controlling ClC‐K2 activity in the CD likely in an Ang II‐AT1R dependent manner. We propose that this mechanism could be instrumental for the discrete CD responses to hypovolemia (when Ang II is high) and hyperkalemia (Ang II is low).Support or Funding InformationThis research was supported by NIH‐NIDDK DK095029 (to O. P.), AHA 17GRNT33660488 (to O. P.), and ASN Ben J. Lipps Research Fellowship (to V. T.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Metformin Blunts Exercise‐Induced Improvements in Skeletal Muscle Mitochondrial Respiration Independent of Changes in Mitochondrial Biogenesis
Authors: Konopka Adam R. , Castor William M. , Reid Justin , Schoenberg Hayden , Laurin Jamie , Wolff Christopher , Hamilton Karyn , Miller Benjamin 
Published: June 2021

The anti‐hyperglycemic agent Metformin and exercise independently prevent the progression from prediabetes to overt type two diabetes (T2D) and are both implicated in healthspan extension. However, emerging evidence indicates the addition of Metformin to exercise may inhibit the health benefits of exercise. The purpose of the current study was to test the hypothesis that Metformin blunts the positive adaptations to exercise by inhibiting skeletal muscle mitochondrial fractional protein synthesis rates (FSR) and respiration. Older adults (n=53, 62±5 yrs) with at least one risk factor for T2D were randomized in a double‐blinded fashion to consume Metformin or placebo (1500–2000 mg/day) during 12‐weeks of aerobic exercise training (AET). VO2max and skeletal muscle mitochondrial respiration were assessed before (PRE) and after (POST) the 12‐week intervention. Skeletal muscle biopsy samples were obtained 48 hrs after the last exercise bout and 36 hrs after the last metformin dose. High‐resolution respirometry was performed on permeabilized skeletal muscle fibers to assess submaximal and maximal oxidative phosphorylation (OXPHOS; P) primarily linked to complex‐I (CIP), fatty acid oxidation (CIP&FAO), and complex II (CI+IIP&FAO). Subsequent addition of FCCP determined maximal uncoupled electron transport system (ETS) capacity. During the last four weeks of the intervention, participants consumed the stable isotope deuterium oxide (2H2O) to measure cumulative FSR (%/day) in a mitochondrial enriched skeletal muscle fraction. Compared to placebo, Metformin tended (P=0.10) to attenuate the increase in VO2max after 12 weeks of AET (Metformin: 0.06±0.02 vs. Placebo: 0.13±0.03 L/min). Congruent with these findings, Metformin abrogated (P<0.05) the exercise‐mediated increase in submaximal mitochondrial respiration, CIp, CI+IIP, and CI+IIP&FAO after AET (Metformin: −0.7 to 2.6 vs Placebo: 5.3 to 22.8 pmol/s/mg tissue). Unlike the effect of Metformin on mitochondrial respiration, mitochondrial protein synthesis rates assessed during AET were not different between Metformin and placebo (1.06±0.05 vs. 1.00±0.04 %/day; P=0.38). Here we demonstrate that metformin tended to diminish the improvement in VO2max and inhibited the increase in skeletal muscle mitochondrial respiration after AET in older adults at risk for T2D. However, the effects on mitochondrial respiration do not appear to be related to changes in mitochondrial biogenesis. Future research is warranted to determine mechanisms by which metformin influences skeletal muscle mitochondrial respiration and impacts the health benefits of exercise.Support or Funding InformationThis study was supported by the National Dairy CouncilThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CHARACTERISATION OF NF‐KB ACTIVATION IN REGENERATING FIBRES OF OLD MICE
Authors: Owen Euan David , Pollock Natalie , Jackson Malcolm Joseph , Vasilaki Aphrodite , McArdle Anne 
Published: June 2021

Sarcopenia is the age‐related loss of muscle mass and function. In human studies a decrease of up to 50% in muscle mass and function is observed from the ages of 25 to 70 years and this contributes significantly to frailty and loss of independence in the ageing population. An increase in pro‐inflammatory cytokines is associated with many age‐related conditions including sarcopenia (particularly TNF‐alpha and IL‐6). Many inflammatory processes are under the direct influence of the NF‐κB pathway and a chronic activation of NF‐κB has been shown in muscles from old mice and in accelerated models of muscle ageing (eg. Vasilaki et al, 2006). Additional studies using immunofluorescent antibody staining demonstrated the presence of p65 (a subunit of NF‐κB) only in muscle fibres containing centrally located nuclei, suggesting that NF‐kB was only active in regenerating muscle fibres.The aim of this study was to determine the extent and nature of activation of NF‐kB during regeneration in a well established mouse model of muscle degeneration and regeneration using the myotoxin, barium chloride (BaCl‐2‐). BaCl‐2‐ was injected into the extensor digitorum longus (EDL) muscles of adult (8 months) and old (22 month) wild‐type (WT) C57BL/6 mice. At defined time points the muscles were quickly excised, weighed and frozen in OCT for transverse sectioning. Changes in muscle morphology were observed through haemotoxylin and eosin staining while fluorescently labelled antibodies against p65 targeted the cellular localization of NF‐κB.Centrally located nuclei were present in the majority of the fibres at 14, 28 and 60 days post BaCl2 injection. Nuclear translocation of p65 was seen 14 and 28 days post BaCl2 injection indicating activation of the canonical NF‐κB pathway in regenerating fibres.The results of these experiments reveal an association between muscle fibre regeneration and activation of the canonical NF‐κB pathway. Further studies will determine the effect of activation of NF‐kB during regeneration on inflammatory gene expression and compare with activation in ageing models.Support or Funding InformationFunded by the National Institutes of Health (NIA).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.