bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Acute Dietary Nitrate Supplementation on Exercise Blood Flow in Hypertension: Does Medication Status Matter?
Authors: La Salle D. Taylor , Broxterman Ryan M , Ratchford Stephen M. , Richardson Russell S. , Trinity Joel D. 
Published: June 2021

Dietary nitrates are effective at lowering resting blood pressure (BP) in humans and improving skeletal muscle blood flow (BF) during exercise in animals. However, evidence of improved BP status and BF during exercise in hypertension is lacking. The purpose of this investigation was to determine if acute (3‐day) nitrate supplementation with beetroot juice (BR) lowers BP and augments BF in hypertensive individuals on and off antihypertensive medication during progressive handgrip (HG) and single‐leg knee extension (KE) exercise. In a double blind crossover study, placebo (nitrate depleted BR) and BR were administered in 14 subjects with controlled hypertension (ON‐MEDS; 53±11 yrs., 11 men, 3 women) and 14 subjects not taking antihypertensive medications (OFF‐MEDS; 49±13 yrs., 11 men, 3 women). Following either 3 days of BR or placebo supplementation, participants performed HG (15, 30, 45% of maximal voluntary contraction [MVC]) and single‐leg KE exercise (40, 60, 80% of work rate maximum [WRmax]). When OFF‐MEDs, BR significantly reduced resting diastolic BP (DBP) (BR: 84 ± 3 vs. PL: 88 ± 3 mmHg; p < 0.01) and mean arterial pressure (MAP) (BR: 101 ± 3 vs. PL: 106 ± 3 mmHg; p < 0.01), with systolic BP (SBP) trending lower (BR: 136 ± 4 vs. PL: 141 ± 5 mmHg; p = 0.067). BR did not change resting BP for the ON‐MEDS group. During HG exercise, BR supplementation only lowered SBP at 15% MVC (p < 0.05) and 30% MVC (p = 0.05) when OFF‐MEDS, with no effect on BF or vascular conductance (VC). During KE exercise, in the OFF‐MEDS group, BR significantly lowered SBP and MAP at 80% WRmax, but not at the lower intensities. When OFF‐MEDS, BR significantly increased leg BF at 40% WRmax (BR: 2667 ± 173 vs. PL: 2461 ± 193 ml/min; p = 0.04) and leg VC at 40% (BR: 24 ± 2 vs. PL: 21 ± 1 ml/min/mmHg; p < 0.01) and 60% (BR: 27 ± 2 vs. PL: 25 ± 2 ml/min/mmHg; p < 0.03) WRmax. When ON‐MEDS, BR did not alter BP, BF or VC during HG or KE exercise. These findings reveal that BR can lower BP at rest and during exercise, as well as augment the blood flow response during leg exercise in unmedicated hypertensive individuals, suggesting a potential benefit of BR to this population.Support or Funding InformationThis study was supported by Veteran Affairs Rehabilitation Research and Development Grant IK2RX001215 CDA2 (to J. D. Trinity) and American Heart Association Grant 14SDG1850039 (to J. D. Trinity)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhibition of Mitochondrial Fission Improves Mitochondrial Respiratory Capacity in Primary Myotubes Derived from Obese Humans
Authors: Kugler Benjamin A , Hale Margaret , Eugene Nancy , Garcia Jessica , Houmard Joseph A , Zou Kai 
Published: June 2021

Obesity induces mitochondrial fragmentation in skeletal muscle causing reduced mitochondrial respiratory capacity, which has been linked with the development of insulin resistance and type 2 diabetes. Recent evidence suggests that excessive mitochondrial fission is the culprit behind the mitochondrial fragmentation in skeletal muscle from obese humans. The purpose of this study was to determine if inhibiting mitochondrial fission in human skeletal muscle cells derived from severely obese individuals reduces mitochondrial fragmentation and improves mitochondrial respiratory capacity. Human skeletal muscle cells were isolated from muscle biopsies obtained from severely obese, insulin‐resistant subjects (n=6, BMI = 47.3 ± 2.8 kg/m2, HOMA‐IR = 3.4 ± 0.4), pooled and differentiated into myotubes. On day 6 of differentiation, myotubes were treated with either mitochondrial fission inhibitor Mdivi‐1 (20μM) or DMSO for 12 hrs. Mitochondrial respiratory capacity was measured using Seahorse XFp Analyzer. Live cells were stained with MitoTracker, and mitochondrial morphology was examined by confocal microscopy. Mitochondrial fission, fusion, and OXPHOS protein expressions were assessed by immunoblot. All experiments were repeated on three different occasions. Preliminary data indicate that mitochondrial fission protein dynamin related protein (Drp1) was reduced (20.9%, P = 0.093), with no changes in mitochondrial content or mitochondrial fusion proteins. Inhibiting mitochondrial fission resulted in a reduction of mitochondrial networks (9.7%) while increasing mitochondrial branch length (14.7%). Reserved mitochondrial respiratory capacity, as measured by the mitochondrial spare capacity, was significantly increased (31.4%, P < 0.05) with Mdivi‐1 treatment. These results demonstrate that inhibition of mitochondrial fission improves mitochondrial morphology and respiratory capacity in skeletal muscle from obese humans, suggesting mitochondrial fission may be a novel therapeutic target for treating metabolic disorders that are typically linked to mitochondrial dysfunction.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Altered skeletal muscle redox status, structural integrity, and ryanodine receptor are associated with contractile dysfunction following systemic iron loading in mice
Authors: Liang Chen , Mickey Marisa C , Receno Candace N , Atalay Mustafa , DeRuisseau Keith C 
Published: June 2021

We previously reported that a moderate degree of systemic iron loading caused muscle functional impairment in mice. Such deterioration was not attributed to oxidative stress since it did not incur protein or lipid oxidative damage. On the other hand, muscle contractile dysfunction was associated with increased thioredoxin protein levels, suggestive of altered redox signaling. Thus, the purpose of this study was to further examine skeletal muscle redox status and potential meditators of contractile dysfunction following a physiologically‐relevant degree of iron loading. Twelve‐week‐old male CD‐1 mice received subcutaneous injections of iron (4 mg iron dextran/200 μL) or vehicle 5 days/week for 2 weeks (n=10/group). One day following the last injection the gastrocnemius muscles were harvested for measurement of biochemical parameters. Systemic iron loading elevated the muscle non‐heme iron (NHI) concentration by approximately 4‐fold (P < 0.001). Although reduced glutathione GSH (P = 0.39) and glutathione peroxidase (GPX) activity (P = 0.82) measures were similar between the two groups, iron‐loaded mice displayed greater glutathione disulfide (GSSG; P = 0.03) and GSSG/GSH ratio (P = 0.03), which are sensitive markers of oxidative stress and redox status. In addition, redox regulator glutaredoxin‐2 (GRX2) protein expression was lower in the muscle of iron‐loaded mice compared with controls (P = 0.04). Muscle structural integrity marker αII‐spectrin at 240 kDa was lower in the iron‐loaded muscles compared with controls (P = 0.02). No differences were observed in its cleavage products at 150 kDa (P = 0.41) or 120 kDa (P = 0.11). Similar to αII‐spectrin, protein levels of focal adhesion α‐actinin were also lower in the iron‐loaded gastrocnemius (P = 0.04). Levels of calstabin‐1 associated with ryanodine receptor (RyR1) were lower in iron‐loaded muscles compared with controls (P = 0.04), while total RyR1 (P = 0.99) was similar between groups. In summary, contractile dysfunction that results from moderate iron loading may be mediated by a disturbance in the muscle redox balance and from changes arising from an increased proteolytic response and aberrant sarcoplasmic reticulum Ca2+ release.Support or Funding InformationSupported by the Syracuse University SOEThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
F‐box and WD‐40 Domain Protein 5 (Fbxw5) and F‐box Protein 44 (Fbxo44) are Expressed in Skeletal Muscle
Authors: White Adrianna , Parke Jane , Waddell David 
Published: June 2021

Skeletal muscle atrophy is a physiological condition that is caused by a myriad of conditions, including immobilization, denervation, spinal cord injury and corticosteroid use and results in decreased muscle size and strength. The molecular genetic events of neurogenic atrophy were analyzed in a previous study using gastrocnemius muscle isolated from mice following 3 days and 14 days of denervation. The gene expression profile in the denervated muscle tissue was analyzed by microarray and compared to control muscle tissue to identify novel genes that are differentially expressed in response to neurogenic atrophy. The microarray data revealed for the first time that F‐box and WD‐40 Domain Protein 5 (Fbxw5) and F‐box Protein 44 are expressed in skeletal muscle and are differentially regulated in response to denervation. Fbxw5 and Fbxo44 are classified as E3 ubiquitin ligases and both have been found to interact with cullin 4 and DNA damage binding protein 1 (DDB1) complexes. Furthermore, Fbxo44 has been found to ubiquitinate and destabilize both BRCA1 and regulator of G protein signaling 2 (RGS2), while Fbxw5 has been shown to destabilize DLC1, a RhoA GTPase‐activating protein, and tuberous sclerosis complex 2 (TSC2), a negative regulator of mTOR. To confirm that Fbxw5 and Fbxo44 are expressed in muscle, quantitative PCR (qPCR) was used to assess the expression levels of these two E3 ligases in both proliferating and differentiated muscle cells and the results demonstrate that expression levels appear to remain relatively constant in proliferating myoblasts and differentiated myotubes. Furthermore, Western blot analysis supported the qPCR data and showed that Fbxw5 and Fbxo44 protein levels remain relatively constant as cultured myoblasts differentiate to myotubes. The discovery that Fbxw5 and Fbxo44 are expressed in skeletal muscle and are differentially regulated in response to neurogenic atrophy helps further our understanding of the molecular genetic events of muscle wasting and may eventually lead to the identification of new therapeutic targets for the treatment and prevention of atrophy.Support or Funding InformationThe work was support by University of North Florida Transformational Learning Opportunity grants and a University of North Florida Foundation Board Grant to D.W.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 sex and exercise training on bone volume and density in Nrf2‐deficient rats
Authors: Wahl John Andrew , Park Hyerim , Barsoum Mina‐Michael , Restrepo Alexis , Dewell Isabella , Wahl Jake , Maraj Joshua , Peterson William , Reid‐Foley Emily , Ballehr Kelsey , Bedwell Kristin , Medarev Steven , Schartz Kaley , Sadowsky Dylan , Delp Michael , Geurts Aron , Muller‐Delp Judy 
Published: June 2021

Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is a transcription factor that is crucial in maintaining cellular redox homeostasis. In female mice, Nrf2 deficiency has been shown to increase bone resorption in the femur. In contrast, treadmill exercise training has been shown to increase bone density in the femur of aged rats. We tested the hypothesis that the absence of Nrf2 would reduce or negate increases in bone density induced by exercise training. We exercise trained male and female wild type Sprague‐Dawley (WT) rats, and their littermates lacking the Nrf2 gene (Nrf2KO). Rats were either exercise trained (EX) on a motor‐driven treadmill 5 days/wk or remained sedentary (SED) in their cages for 10–12 weeks. A mixed moderate aerobic and high‐intensity interval training protocol was utilized. At the end of the training period, femurs were cleaned, then scanned and analyzed using a Scanco Medical uCT35 micro‐CT with a resolution of 12 micron‐voxels. Total volume, bone volume, bone volume/total volume (BV/TV), connectivity and number of trabeculae were evaluated in trabecular bone. In both WT and Nrf2KO male rats, exercise training increased trabecular number (EX: 2.8 ± 0.1 vs. SED: 2.4 ± 0.1; P<0.05) and BV/TV (EX: 0.17± 0.01 vs. SED: 0.13 ± 0.01; P=0.06), and tended to increase connectivity (EX: 31.9 ± 2.5 vs. SED: 24.7 ± 2.5; P=0.09). Surprisingly, total volume, bone volume, BV/TV, connectivity and number of trabeculae were all more than 100% higher in femurs from females as compared to males (female vs. male; P<0.0000001 for all parameters). There were no significant effects of training or Nrf2KO genotype on bone parameters in females. These data suggest that female hormones are powerful regulators of bone growth and remodeling, masking the effects of either deletion of the Nrf2 gene or treadmill exercise.Support or Funding InformationNIH Grant Number R15AG055029This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of Exercise Training and Exercise Training plus Kinesio Taping on Cartilage and Synovial Markers and Pain in Patients with Knee Osteoarthritis
Authors: Okudan Nilsel , Belviranli Muaz , Oguz Ramazan 
Published: June 2021

Establishing prevention and therapeutic strategies for osteoarthritis (OA) is necessary to minimize functional disability and the impact of the disease on society. Therefore, the aim of this study was to investigate the effect of exercise training and exercise training plus kinesio taping technique on cartilage and synovial markers and pain at rest and 20 minutes after the walking exercise in patients with knee OA. The study protocol was approved by Local Ethical Committee of Faculty of Medicine, Selçuk University. Twenty‐two female patients aged between 38–60 years who were diagnosed with OA according to the criteria of the American Rheumatology Association participated in this study. The participants were divided into exercise training and exercise training plus kinesio taping groups randomly. The functional status of the patients was assessed using the Western Ontario and McMaster Universities OA index (WOMAC). Pain assessment was performed on a visual analogue scale (VAS). Participants were invited to the laboratory twice before and after treatment. The blood samples were taken at rest and immediately after the 20‐min walking exercise before treatment and 6‐week after the application of exercise training or exercise training plus kinesio taping technique. Cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)‐1 and ‐3 concentrations were measured in these samples. In patients with knee OA, VAS and WOMAC scores significantly decreased after the exercise training or exercise training plus kinesio taping (P < 0.05). Plasma MMP‐1 and MMP‐3, and serum COMP concentrations significantly increased immediately after 20‐min of walking exercise both before and after treatment (P < 0.05). Resting serum COMP concentrations did not significantly differ after 6 weeks of exercise training when compared to the pre‐treatment (P > 0.05). However, resting serum COMP concentration decreased with exercise training plus kinesio taping technique (P < 0.05). Plasma MMP‐3 concentration decreased with both exercise training or exercise training plus kinesio taping technique (P < 0.05). However, plasma MMP‐1 concentrations did not differ between groups after treatment (P > 0.05). As a result, exercise training and exercise training plus kinesio taping reduced pain and improved functional capacity in patients with knee OA. Additionally, exercise training plus kinesio taping showed a positive effect on cartilage and synovial destruction, but only exercise training showed a positive effect on synovial destruction.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 3‐bormopyruvate on the growth of castration‐resistant prostate cancer
Authors: Wu Yen‐Hsuan , Wu Hsin‐En , Li Chia‐Yang 
Published: June 2021

Prostate cancer (PCa) is the second most frequently diagnosed cancer and the sixth leading cause of cancer death among men worldwide. Androgen deprivation therapy has been the mainstay of treatment for patients with advanced PCa; however, the majority of patients will eventually develop a poor prognosis stage of castration resistant prostate cancer (CRPC) and lead to mortality. For the treatment of CRPC, the therapeutic efficacy of currently treated drugs for CRPC is limited. Therefore, development of new agents for treating CRPC is urgently needed.3‐bormopyruvate (3‐BP) 3‐bromopyruvic acid (3‐BP) is a pyruvate analogue with anti‐tumor activity in breast cancer, pancreatic cancer, colon cancer, liver cancer. However, the effect of 3‐BP on the growth of CRPC remains unclear. In the present study we tested the effects of 3‐BP in CRPC including cell growth, cell cycle progression, cell apoptosis, migration, and the therapeutic efficiency of combination therapy with chemotherapy. Our results showed that 3‐BP inhibited the growth rate of cells, induced G2/M phase arrest, increased cell apoptosis, attenuated cell migration, _and promoted the therapeutic efficiency of combination therapy with chemotherapy in prostate cancer cells. These results suggest that 3‐BP has potential to be a therapeutic agent for treating CRPC.Support or Funding InformationThis study was supported by the Ministry of Science and Technology, Taiwan, R.O.C. (Grant No. MOST 107‐2320‐B‐037‐019).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 differential expression of cytokines secreted by rhesus monkeys bone marrow mesenchymal stromal cells on age‐related bone aging and autophagy
Authors: Liu Fei , Li Yuanmin , Zhang Jie , Lu Yanrong , Chen Younan , Cheng Jingqiu 
Published: June 2021

BackgroundAging is a gradual process characterized by a deterioration in the function of the organism. Studies have shown that there may be a close relationship between organ/tissue aging and stem cells. In addition, progressive DNA damage and mitochondrial dysfunction are considered to be major causes of natural aging. Moreover, autophagy plays an important role in maintaining skeletal homeostasis, and changes in this pathway are associated with osteoporosis. Therefore, the search for age‐related bone aging mechanisms can explain the progressive decline of organs and the development of diseases associated with advanced age, and can clarify the ways in which the relevant therapeutic methods are developed.MethodsWe isolated bone marrow mesenchymal stem cells (rBMSCs) from aged, middle‐aged, and young rhesus monkeys and cultured them to passage 3, followed by transcriptome sequencing of three different age‐derived cells to explore aging‐related GO term and KEGG Pathway. Further analysis of hub genes were performed by gene co‐expression network analysis. In addition, we also measured telomerase activity, cell death and β‐galactosidase staining in rBMSCs of different ages.ResultsWe successfully isolated and cultivated old, middle and young rBMSCs. As shown in Figure 1D, aged rBMSCs stained the most prominent positive galactosidase, while Figure 1C showed that the telomerase activity of rBMSCS gradually decreased from young to old, and the same results also be obtained by cell death analysis and cell culture supernatants (Figure 1A, B). In addition, we found the enrichment of aging‐related genes through both GO term and KEGG pathway analysis (Figure 2). Eleven hub genes were further obtained by the protein interaction map, including LRRC17, VILL, PENK, IFIT1B, MX1, PTGFR, GJB2, IFI44L, CHI3L, LOC718478, GBP2 (Figure 3).Among them, LRRC17 has been reported to participate in and maintain bone homeostasis of osteoblasts and osteoclasts.ConclusionsWe initially explored the effects of age on rBMSCs and possible hub genes in the aging process. The aging characterization of rBMSCs in different age groups all showed a significant decreasing trend. Eleven key factors, including LRRC17, may be involved in the process of bone aging. Taken together, these results suggest several new key factor in bone aging and related aging pathways.Support or Funding InformationThis work was supported by the Chengdu Giant Panda Breeding Research Foundation (CPF2015‐08).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
IP3‐evoked Ca2+ release in Endothelial Cells is Modulated by the Immunosuppressant FK506‐binding Protein (FKBP12)
Authors: Buckley Charlotte , Wilson Calum , McCarron John 
Published: June 2021

The endoplasmic reticulum (ER) is integral to the regulation of cytoplasmic Ca2+ concentration in endothelial cells. Ca2+ release from the ER is controlled by two intracellular receptor/channel complexes, the inositol 1,4,5‐triphosphate receptor (IP3R) and the ryanodine receptor (RyR). These receptors have been shown to be regulated by the accessory FK506‐binding protein (FKBP). FK506 is a potent immunosuppressant, which is routinely used after organ transplant to lower the risk of rejection, and has also been used in drug‐eluting stents. FK506 has been shown to act on smooth muscle cells either directly by binding to the channel, or indirectly via FKBP modulation of two targets, calcineurin or the mammalian target of rapamycin (mTOR). However very little is known on the role FKBPs play in endothelial cell Ca2+ signaling.To investigate this, Ca2+ signals were measured in the endothelium of second order mesenteric arteries using Cal‐520 (5 μM). IP3Rs were activated by localised photo‐uncaging of IP3 (5 μM), and RyR by the application of Caffeine (10 mM). FK506 (10 μM), which displaces FKBP from each receptor to inhibit calceinurin, increased the IP3‐evoked Ca2+ rise. The phosphatase inhibitors cypermethrin and okadaic acid also increased the IP3‐mediated Ca2+ release. Cypermethrin and okadaic acid did not prevent FK506‐induced increase in Ca2+ release. These results suggest that while calceinurin may modulate IP3‐evoked Ca2+ release, the phosphatase is not necessary for the FK506‐mediated potentiation of IP3‐evoked Ca2+ increase.Rapamycin (10 μM), which disrupts the binding of FKBP12 to the receptor and inhibits mTOR, did not significantly alter IP3‐induced Ca2+ release in endothelial cells, indicating that mTOR does not exert a significant role in endothelial IP3‐induced Ca2+ release.Interestingly Caffeine, the activator of RyR‐mediated Ca2+ release, did not activate Ca2+ signals in the endothelium either in intact tissue or in freshly isolated endothelial patches, suggesting that Caffeine‐activated RyRs do not play a role in endothelial Ca2+ release.These results indicate that FKBPs play an integral role in regulating endothelial IP3‐mediated Ca2+ release, and may underlie the severe endothelial dysfunction associated with FK506 immunosuppressants.Support or Funding InformationWellcome TrustBritish Heart FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.