bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired pulmonary function and right ventricular morphology in well‐healed burn survivors is related to aerobic capacity and not severity of burn injury
Authors: Samuel T. Jake , Nelson Michael D. , Nasirian Aida , Jaffery Manall , Moralez Gilbert , Romero Steven A. , Cramer Matthew N. , Huang Mu , Kouda Ken , Babb Tony G. , Sarma Satyam , Crandall Craig 
Published: June 2021

Acute pulmonary dysfunction—second to inhalation injury—is prevalent in burn survivors, and is associated with a 24‐fold increase in morbidity and mortality. Systemic inflammation is known to persist many years post‐injury and likely compromises the pulmonary vasculature and respiratory gas exchange in well‐healed burn survivors. Whether pulmonary dysfunction in this population is related to right ventricular (RV) morphology and function remains unknown. Twenty‐six well‐healed burn survivors (age: 42 ± 14; body mass index: 28.1 ± 5.8; body surface area [BSA] burn: 49 ± 22 [range: 20–88]) and 11 age, sex and activity matched controls (age: 34 ± 9; body mass index: 28.2 ± 5.3) were recruited for assessment of maximal aerobic capacity (VO2max; via a graded cycle ergometer test), pulmonary function (diffusing capacity of the lungs for carbon monoxide [DLCO]) and RV morphology and function (via magnetic resonance imaging). Burn survivors were grouped post‐hoc by DLCO and classified as having either low (≤80% predicted; n = 6; %BSA burn: 42 ± 11), moderate (80–100% predicted; n = 11; %BSA burn: 42 ± 23), or high (>100% predicted; n = 9; %BSA burn: 61 ± 22) diffusing capacity. Group differences in RV morphology and function were assessed by one‐way ANOVA with Bonferroni correction where appropriate, and relationships between variables were assessed by partial correlation after controlling for body mass. Group differences were observed between those with low and high diffusing capacity in RV morphology (RV end‐diastolic volume [EDV] index: 73 ± 10mL/m2 vs. 81 ± 11mL/m2 vs. 95 ± 15mL/m2 vs. 84 ± 13mL/m2, low vs. moderate vs. high vs. control, respectively; ANOVA P = 0.012), but not RV function (RV ejection fraction: 54 ± 7% vs. 51 ± 9% vs. 53 ± 6% vs. 51 ± 10%, low vs. moderate vs. high vs. control, respectively; ANOVA P = 0.94). However, correlational analyses revealed that these group differences were primarily related to maximal aerobic capacity, after controlling for body mass (RV EDV vs. VO2max, r = 0.48, P = 0.003; DLCO vs. VO2max, r = 0.77, P < 0.001; RV EDV vs. DLCO, r = 0.57, P < 0.001). Taken together, we interpret these data to reflect RV remodeling due to lower maximal aerobic capacity, as opposed to frank impairments related to burn‐induced pulmonary dysfunction, and thus support a role for aerobic exercise training to improve cardiac function in well‐healed burn survivors.Support or Funding InformationProject funded by NIH GM068865This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Circulating miR‐122‐5p: A Novel Exerkine in Exercise‐induced Angiogenesis
Authors: Wu Jie , Hou Zuoxu , Li Guohua , Zhang Xing , Gao Feng 
Published: June 2021

Physical exercise effectively boosts angiogenesis in skeletal muscles, but the mechanisms remain poorly understood. Our previous study showed that 4‐week swimming training (1.5 h×2/d, 7 d/wk×4 weeks) significantly promoted angiogenesis in skeletal muscle. And we had found the expression of several circulating miRNAs profoundly changed. Among which, miR‐122‐5p, a liver specific microRNA, promoted endothelial proliferation significantly. Here we further determined the role of circulating miR‐122‐5p in exercise‐induced angiogenesis. Exercised mice (running wheel training, 1.5 h/d ×9 d) exhibited elevated miR‐122‐5p in serum and aorta (2.132±0.294, 3.275±0.819 fold of Sedentary, p<0.05), concomitant with increased capillary density in the quadriceps marked with fluorescent CD31 (3.562±0.354 fold of Sedentary, p<0.01). Whereas, tail vein injection of miR‐122‐5p antagomir partially decreased the exercise‐induced VEGF expression and CD31 staining in quadriceps, suggesting that elevated circulating mir‐122‐5p partially contributes to the exercise‐induced angiogenesis. In vitro study on primary aortic endothelial cells (ECs) transfected with miR‐122‐5p mimic showed increased tube numbers, migration distance and relative sprouting distance, accompanied with increased expression of p‐ERK/ERK and VEGF. Mechanistically, miR‐122‐5p mimic increased the expression of CD36, CPT1a and CPT1b together with the uptake of fatty acid assessed by BODIPY fluorescence intensity in ECs, suggesting an increased free fatty acid (FFA) metabolism. Transfection of CD36 siRNA blunted the pro‐angiogenic effect of miR‐122‐5p. In conclusion, our findings demonstrate that exercise‐induced proangiogenic effects are partly attributed to elevated circulating miR‐122‐5p via increasing endothelial FFA metabolism.Support or Funding InformationThis study was supported by the grants from the National Natural Science Foundation of China (Grant No. 816770253)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exosomal Signaling by Skeletal Muscle: Role in Neuromuscular Ageing
Authors: Hemmings Kay , Girithananda Aarthi , Robertson Rebecca , Pugh Jamie , Scalabrin Mattia , Mora Silvia , McArdle Anne 
Published: June 2021

Muscle mass and function are reduced with age in mammals and this is associated with disrupted neuromuscular interactions. Skeletal muscle mounts a robust stress response to contractions by the increased expression of Heat Shock Proteins (HSPs), which facilitate muscle remodelling, promote protein folding and clearance of damaged proteins. In contrast, other tissues, including neuronal cells are unable to mount a stress response. It has been proposed that HSPs may be transferred from one cell type to another in exosomes to maintain proteostasis in the recipient cells. Further, HSP generation by muscle following contractions is attenuated in old mice and humans. We hypothesise that this inability of muscles of old mice to produce HSPs in response to contractions results in altered exosomal HSP transfer, and therefore a failure to maintain proteostasis in neighbouring cells including motor neurons, with subsequent neuronal and muscle degeneration (1).Single muscle fibres were isolated from flexor digitorum bravis (FDB) muscles of adult (6–12 month) mice, and initiated to contract using a non‐damaging electrical stimulation protocol. Media was collected at time points up to 24hrs, and exosomes were purified from the media using ultracentrifugation approaches. NanoSight analysis was used to characterize and quantify the exosomes, and HSP content analysed by western blotting.Data demonstrated that there was a significant (2–3 fold) increase in exosome release by muscle fibres of adult mice following contraction compared with non‐stimulated controls, and that the exosomal HSP content was also increased. For example, at 4hrs post contraction, there was no increase in HSP25 content of exosomes but a 2 fold increase in HSP60 was detected at this time point compared with non‐stimulated controls. Preliminary data also showed that there was a 3.5 fold increase in HSP25 exosomal content at 24hrs post stimulation.Additional data demonstrated the potential uptake of exosomes labelled with lipophilic carbocyanine fluorescent dye by immortalized neuronal cells. Additional studies will also examine the effect of age on exosome production by muscle fibres, including HSP content and neuronal uptake, by comparison with muscle from CuZn superoxide dismutase (CuZnSOD) null mice, a model of accelerated muscle ageing.Support or Funding InformationWith thanks to National Institute of Ageing (AG051442), the Physiological Society (summer studentship awarded to RR) and the University of Liverpool for their generous 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.
A model of skeletal muscle showing the process of cramp and the mechanism of its relief
Authors: Tasaki Kazuyo Maria , Noble Penelope Jean , Garny Alan , Noble Denis 
Published: June 2021

The research reported here is the first time that skeletal muscle cramp has been modelled using biophysically detailed processes, and the first time that the mechanism of its relief has been identified. We extended the Shorten et al (2007) skeletal muscle model to include sarcolemmal Ca2+ transporters, including ICaL, Na+‐Ca2+ exchange, and Ca2+ pump. When stimulated at 100 Hz the model successfully reproduces cramp, defined as a maintained contraction that does not immediately reverse when stimulation is stopped. The incorporation of ICaL is necessary for the model to reproduce the cramp process since block of ICaL, or using the original model without ICaL, removes the cramp mechanism. A further important process in maintaining cramp is accumulation of interstitial [K+] which produces large membrane depolarization. Relief of cramp is shown to require rapid washout of interstitial [K+]. The resulting hyperpolarization enables Na+‐Ca2+ exchange to promote Ca2+ efflux and so relieve the cramped state (Figure 1).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 the Anticancer Drug Doxorubicin and Dietary Creatine Supplementation on Myogenic Regulatory Factor Expression
Authors: Busekrus Raquel B , Torok Zoltan A , Hydock David S 
Published: June 2021

The purpose of this study was to explore the acute effects of doxorubicin (Dox) treatment on myogenic regulatory factor (MRF) expression and determine the impact that creatine monohydrate (Cr) feeding prior to Dox treatment has on the MRF response. Male Sprague‐Dawley rats were randomly assigned to one of three feeding groups: rodent chow supplemented with 2% Cr for four weeks (Cr1), rodent chow supplemented with 4% Cr for one week followed rodent chow supplemented with 2% Cr for three weeks (Cr2), or standard rodent chow for four weeks (Con). After four weeks, animals in each feeding intervention received a 15 mg/kg bolus Dox i.p. injection or a 0.9% bolus saline i.p. injection as a placebo (Sal). One day after injections, animals were anesthetized, and the extensor digitorum longus (EDL) muscles were excised. Expression of the primary MRFs Myf5 and MyoD and the secondary MRFs myogenin and Mrf4 were then quantified with Western blotting. Creatine feeding promoted an upregulation in Myf5 and MyoD (significant diet effect p=0.022 and p=0.017, respectively), and this upregulation was more profound with MyoD expression in Cr2. Significant diet effects were also observed with myogenin (p=0.0011) and Mrf4 (p<0.001) with Cr1 and Cr2 expressing higher levels of myogenin than Con+Sal (p<0.05) and Cr2 expressing higher levels of Mrf4 than Con+Sal and Con+Dox (p<0.05). In conclusion, Cr feeding prior to Dox treatment increased MRF expression suggesting that Cr may enhance signaling for skeletal muscle repair and regeneration following Dox treatment thereby attenuating muscle damage.Support or Funding InformationDavid S. Hydock, PhD was supported by a Pilot and Exploratory Projects in Palliative Care of Cancer Patients and Their Families, PEP‐17‐193‐01 ‐ PCSM, from the American Cancer Society.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Skeletal Muscle Stretch‐Induced PGE2 Formation does not Impact the Muscle Mechanoreflex in Decerebrate Rats
Authors: Rollins Korynne , Butenas Alec L , Hopkins Tyler D , Felice Kennedy P , Copp Steven W 
Published: June 2021

Mechanical and metabolic signals associated with skeletal muscle contraction stimulate thin fiber muscle afferents and produce reflex increases in blood pressure (i.e., the exercise pressor reflex). There is an interplay between those signals as metabolites may sensitize afferent responsiveness to mechanical signals. A common strategy used to study the mechanical component of the exercise pressor reflex (i.e., the mechanoreflex) in isolation from the metabolic component is to measure the reflex increase in blood pressure during passive hindlimb muscle stretch in an experimental animal preparation. Passive muscle stretch has been presumed to impart a purely mechanical stimulus. However, intermittent but not static mechanical stimulation of cultured skeletal muscle cells was found to increase PGE2 production and PGE2 has been shown to sensitize the muscle mechanoreflex. Based on those findings, the purpose of this investigation was to test the hypothesis that in decerebrate, unanesthetized rats, dynamic but not static hindlimb skeletal muscle stretch would increase interstitial PGE2 concentration. Moreover, we tested the hypothesis that COX inhibition with indomethacin would attenuate the stretch‐induced increase in PGE2 concentration and the increase in blood pressure during mechanoreflex activation. Experiments were performed on 28 young adult male Sprague‐Dawley rats. The microdialysis technique was used to collect triceps surae muscle interstitial fluid at rest and during 4 minutes of 1 Hz dynamic muscle stretch and 4 minutes of static muscle stretch (performed in random order and separated by 10 minutes). Muscle stretch was performed by manually turning the rack and pinion. We found that triceps surae muscle interstitial PGE2 concentration was significantly increased during both static (↑38%, p=0.01) and dynamic (↑56%, p<0.01) stretch above their respective baseline concentrations (n=9). Indomethacin (1μg/kg) significantly reduced baseline PGE2 concentration and prevented the increase in PGE2 during static (n=4) and dynamic (n=5) stretch. Importantly, indomethacin had no effect on the peak pressor response during static (control: 15±4, indomethacin: 16±4 mmHg; p=0.82) and dynamic (control: 17±2, indomethacin: 18±4 mmHg; p=0.68) stretch (n=7). Collectively, these data indicate that static and dynamic hindlimb muscle stretch in decerebrate, unanaesthetized rats increased muscle interstitial PGE2 concentration. The magnitude of increase in PGE2, however, was not sufficient to impact the muscle mechanoreflex.Support or Funding Information1R01HL142877 to SWCThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Attenuated Skeletal Muscle Contraction‐Induced Rapid Onset Vasodilation in African Americans
Authors: Kaur Jasdeep , Barbosa Thales C. , Young Benjamin E. , Stephens Brandi Y. , Nandadeva Damsara P. , Brothers R. Matthew , Fadel Paul J. 
Published: June 2021

A number of studies have demonstrated that African Americans (AA) have a blunted ability to vasodilate at rest compared to Caucasian Americans (CA). Recently, our laboratory has demonstrated that AA have an attenuated forearm vascular conductance (FVC) response to rhythmic handgrip exercise at moderate and high intensities. Whether these differences in vasodilation also occur at the immediate onset of exercise remains unknown. Herein, we tested the hypothesis that AA subjects have an attenuated increase in FVC following a single muscle contraction, compared to CA subjects. A single muscle contraction model was chosen since it allows for isolation of rapid and robust local vasodilatory responses that are independent of large changes in systemic hemodynamics or sympathetic activation. Young, healthy AA (n = 4) and CA (n = 4) men performed single forearm contractions at 20%, 40%, and 60% of their maximum voluntary contraction (MVC). Heart rate (ECG), arterial blood pressure (Finometer), and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured. FVC was calculated as forearm blood flow (FBF)/mean arterial pressure (MAP). Baseline FVC (CA: 1.04 ± 0.18 and AA: 1.31 ± 0.11 ml/min/mmHg; p = 0.26), FBF (CA: 99.5 ± 16.1 and AA: 105.9 ± 8.7 ml/min; p = 0.54), MAP (CA: 82 ± 2 and AA: 84 ± 2 mmHg; p = 0.46) and MVCs (CA: 56 ± 1 and AA: 58 ± 3 kg; p = 0.45) were similar between the groups. Following single forearm contraction, both groups exhibited intensity‐dependent increases in FBF and FVC; however, these responses were significantly attenuated in AA at all intensities compared to CA. For instance, in response to 20% MVC single contractions, AA had a 34 ± 10% increase in FVC from baseline compared to a 86 ± 31% increase in CA (mixed‐model ANOVA; p < 0.001), and in response to 60% MVC single contractions, AA had a 132 ± 9% increase in FVC from baseline compared to a 198 ± 30% in CA (mixed‐model ANOVA; p < 0.001). These preliminary data suggest that AA have blunted vasodilation in response to single forearm contractions at mild, moderate and high‐intensity workloads.Support or Funding InformationSupported by UTA College of Nursing and Healthy InnovationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Aged neutrophils fuel tumor progression: Good cells gone bad
Authors: Mittmann Laura Alice , Schaubaecher Johanna B. , Hennel Roman , Lauber Kirsten , Uhl Bernd , Reichel Christoph A. 
Published: June 2021

Neutrophilic granulocytes (neutrophils) represent the first immune cells recruited to the site of injury or infection. Beyond their well‐established role in inflammatory pathologies, these leukocytes are increasingly recognized to modulate initiation, progression, and metastasis of cancer. Recently, ageing of mature neutrophils in the circulation has been identified to be critical for proper immune responses in inflammatory scenarios. The fate and function of aged neutrophils in malignant disorders, however, remain elusive. Here, we demonstrate for the first time that particularly aged neutrophils are recruited to malignant tumors as evidenced in heterotopic (multi‐channel in vivo microscopy) and orthotopic mouse models (multi‐channel flow cytometry) of mammary or head and neck carcinoma. Mechanistically, tumor‐released damage associated molecular patterns (DAMPs) including S100A8/9 and uric acid, but not high mobility group box 1 (HMGB1), initiate responses of these ‘experienced’ immune cells by activating the multimeric intracellular NLRP3 inflammasome (but not NLRP1, AIM2, or NLRC4 inflammasomes) in peritumoral macrophages. This leads to the release of cytokines that, in turn, activate microvascular endothelial cells, ultimately promoting the trafficking of aged neutrophils to neoplastic lesions. Most interestingly, aged neutrophils were found to exhibit a pro‐tumorigenic ‘N2’ phenotype. Accordingly, blockade of NLRP3 activation almost completely abolished responses of aged neutrophils in the peritumoral microvasculature as well as the subsequent infiltration of these immune cells into malignant lesions. Concomitantly, NLRP3 inhibition severely compromised tumor growth to the level of neutrophil‐depleted animals in these experiments, but did not directly affect the proliferation of cancer cells in vitro. Thus, our experimental data uncover a previously unappreciated role of aged neutrophils as potent regulators of tumor progression. Interfering with the recruitment of these immune cells to malignant lesions might emerge as a promising immunotherapeutic strategy to prevent advanced stages of cancer.Support or Funding InformationThis study was supported by Deutsche Forschungsgemeinschaft (DFG), Sonderforschungsbereich (SFB) 914.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anti‐inflammatory effects of punicalagin on LPS‐activated microglia
Authors: Lee Yueh‐Shan , Lai Yi‐Xin , Li Chia‐Yang 
Published: June 2021

Pomegranate (Punica granatum L.) is a popular fruit originated in the Middle East and has been widely planted around the world. It contains various phytochemicals such as polyphenolic compounds and has a wide range of biological activities, including anti‐inflammatory, anti‐tumor, antibacterial, and anti‐oxidant activities. Among many polyphenols of pomegranate, punicalagin is the main component of pomegranate polyphenols. However, the effect of punicalagin on immunoregulation has not been well examined. Since inflammation is associated with several neurodegenerative diseases, the inhibition of inflammatory response has benefit to delay the progression of the neurodegenerative diseases. Hence, the aim of this study is to examine whether punicalagin affects LPS‐induced inflammatory responses in BV2 murine microglial cells. Cell viability was analyzed by MTT assay. The production of nitric oxide (NO) was determined by Griess reagent assay. The expression of cyclooxygenase‐2 (COX‐2), inducible NO synthase (iNOS) and mitogen‐activated protein kinases (MAPKs)‐related proteins was examined by Western blot. The production of pro‐inflammatory cytokines, interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α (TNF‐α), was detected using ELISA. Our experimental showed that punicalagin inhibits NO production, attenuates COX‐2 and iNOS expression, decreases IL‐1β, IL‐6 and TNF‐α production in LPS‐activated BV2 microglial cells. In addition, we also found that punicalagin inhibits the phosphorylation of ERK, JNK, and P38 in LPS‐activated BV2 microglial cells. Collectively, these results pointed out that punicalagin has anti‐inflammatory activities in LPS‐activated BV2 microglial cells and suggest that punicalagin might have benefit in attenuating brain inflammation and delaying the progression of the neurodegenerative diseases.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.