bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prior eccentric exercise modifies diving‐induced inflammatory gene expression in rats
Authors: Eftedal Ingrid , Jørgensen Arve , Flatberg Arnar 
Published: June 2021

Decompression sickness (DCS) after diving is a major risk of injury to divers, aviators and space travelers. DCS is associated with gas bubbles formed during decompression, but the processes linking bubbles to DCS are unknown. Exercise before diving reduces DCS risk. The effect of exercise on DCS could be caused by reduced bubble formation and/or to the induction of genetic pathways that affect biological responses to bubbles.Study objectiveTo examine the effects of eccentric exercise on vascular gene expression and gas bubble production after diving.MethodsThree groups of female Sprague Dawley rats were used; two diving groups with or without exercise and one control group, n=9 in each group. The exercise group did one bout of 100 min downhill treadmill running before diving, and saturation diving was simulated in an air‐filled pressure chamber at 709 kPa for 50 min. Diving‐induced stress was measured by ultrasonic detection of bubbles in the pulmonary artery and by full genome mRNA analysis of the aorta. All procedures were approved by the Animal Research Ethics Authority.ResultsDiving alone activated expression of 18 genes, whereas eccentric exercise reduced expression of 12 of these and upregulated an additional 25 genes. Specifically, elevated cytokine‐cytokine receptor expression and decreased expression of anti‐fibrinolytic Serpine1 was found in the exercise group. There were no differences in bubble formation between the groups.ConclusionsWhereas diving induces cytokine and oxygen‐responsive gene expression, the protective effect of eccentric exercise before diving may be attributed to altered expression of genes involved in inflammatory responses.This study was supported by Samarbeidsorganet HMN/NTNU, Kontaktutvalget St. Olavs Hospital/NTNU, and FUGE Midt‐ Norge, Norway.
Drosha‐dependent miRNA regulate aldosterone synthesis by increasing StAR and HSD3B2 expression
Authors: Oki Kenji , Gomez-Sanchez Elise P , Gomez-Sanchez Celso E 
Published: June 2021

Drosha initiates the production of miRNAs from precursors. To study the functions of miRNA in adrenal steroid production, we knocked down Drosha expression in the HAC15 cell, a subclone of the H295R human adrenocortical cell, using lentiviral vectors to deliver shRNA of Drosha. Drosha protein levels in the infected HAC15 cells were reduced by 74.3% compared to empty vector infected control cells. Drosha knock‐down led to 36.3% and 46.4% suppression of aldosterone production under basal and after angiotensin II (A‐II) stimulated conditions, respectively. Basal and A‐II stimulated StAR and HSD3B2 mRNA expression levels in the Drosha knock‐down cells were also significantly suppressed; expression of other enzymes required for aldosterone synthesis were not altered. In conclusion, suppression of Drosha significantly diminished basal and A‐II stimulated StAR and HSD3B2 mRNA expression and aldosterone production, suggesting that at least one miRNA is essential for aldosterone production.Support: VA Medical Research Funds, NIH HL27255 & HL75321
Steroidhormones in the saliva of children after acute physical stress in school
Authors: Budde Henning , Windisch Claudia , Wegner Mirko , Arafat Ayman , Voelcker-Rehage Claudia 
Published: June 2021

Acute bouts of physical activity can influence the secretory processes of the adrenal cortex releasing cortisol (C) in adolescents (Budde et al., 2010). After 12 minutes of exercise and an adequate workload of > 70% of the HFmax adolescents revealed increased salivary C levels (Budde et al., 2010).The aim of our study was to assess to what extent these results are replicable in primary school students.53 students of a 4th grade (9–10 years of age) were randomly assigned to an experimental (EG) and a control group (CG). Saliva collection took place after a normal school lesson (pre‐test) and 5 minutes after a 12‐min. control condition (movie watching) (CG, n = 21) or intensive exercise in a defined heart rate (HR) interval (EG, n = 32) (post‐test).Repeated measures ANOVA showed a significant interaction between group (EG, CG) and test session (pre‐test, post‐test), F (1,49) = 5.00, p = .030, Î·2 = .093, pointing to a different response to physical exercise for the EG compared with the CG. However, post‐hoc t‐tests showed no significant increase of C concentration in the EG, but a significant decrease of C in the CG from pre‐ to post‐test.Results, also for testosterone, are being discussed.
Effect of the peroxisome proliferator‐activated receptor gamma (PPARγ) agonist Rosiglitazone on the hypothalamic GT1‐7 cell line
Authors: Hwang Vicky , Fernandez Marina Olga , Webster Nicholas Julian 
Published: June 2021

Polycystic ovary syndrome (PCOS) is a major cause of infertility in women and is linked to obesity and insulin resistance. Rosiglitazone, a PPARγ agonist, increases insulin sensitivity and improves PCOS and diabetes. PPARγ ligands have also been found to affect the hypothalamus‐pituitary‐gonadal axis, although their site and mechanism of action are not entirely known. The aim of this study was to determine the effects of rosiglitazone on insulin and kisspeptin stimulation of GT1‐7 hypothalamic GnRH neurons. Timecourse and dose response experiments were conducted using 24 hour pretreatment of rosiglitazone or vehicle, and with either insulin or kisspeptin stimulation. Akt and ERK phosphorylation were analyzed with Western Blot and GnRH mRNA expression was analyzed with RT‐QPCR. Preliminary results indicated that treatment with rosiglitazone increased insulin‐induced phosphorylation of Akt in GT1‐7 cells. Maximal stimulation occurred between 10 and 15 minutes, and an insulin concentration of 10 nM. Kisspeptin alone increased GnRH mRNA, with maximal stimulation at 1 nM, as reported by others. Furthermore, rosiglitazone appears to increase kisspeptin induced GnRH mRNA. In conclusion, rosiglitazone appears to have a direct role in regulating hypothalamic GT1‐7 neurons by acting as an insulin sensitizer and modulating the effects of kisspeptin.Supported by NIH grant U54HD12303. VH was supported by Julia Brown Undergraduate Research Scholarship.
PERIPHERAL PRAZOSIN COMBINED WITH NORADRENALINE INTO THE LATERAL PARABRACHIAL NUCLEUS FACILITATES CHOLINERGIC‐INDUCED SODIUM APPETITE
Authors: Gasparini Silvia , Gomide Joelma Maria Cardoso , Andrade-Franzé Glaucia Maria Fabricio , Andrade Carina Aparecida Fabricio , de Almeida Colombari Débora Simões , De Luca Laurival Antônio , De Paula Patrícia Maria , Moreira Thiago Santos , Menani José Vanderlei 
Published: June 2021

ObjectivesIn the present study, we investigated the effects of the combination of noradrenaline into the LPBN and prazosin (α1‐adrenoceptor antagonist) intraperitoneally (ip) on water and 0.3 M NaCl intake in rats treated with ip injection of the cholinergic agonist pilocarpine.Methods and resultsMale Holtzman rats with bilateral stainless steel guide‐cannulas implanted into LPBN were used. Pilocarpine (1 mg/kg) injected ip induced water intake (2.9 ± 0.3 ml/180 min), without affecting 0.3 M NaCl intake (0.5 ± 0.3 ml/180 min). Bilateral injections of noradrenaline (80 nmol/0.2 μl) into the LPBN combined with ip prazosin (1 mg/kg) increased ip pilocarpine‐induced water intake (6.3 ±1.7 ml/180 min) and 0.3 M NaCl intake (14.7 ± 3.5 ml/180 min). LPBN noradrenaline injections combined with ip saline did not affect 0.3 M NaCl (0.8 ± 2.4 ml/180 min) and decreased water intake (0.8 ± 0.3 ml/180 min) induced by ip pilocarpine. Prazosin ip did not modify 0.3 M NaCl (4.8 ± 3.6 ml/180 min) or water intake (0.5 ± 0.3 ml/180 min) in rats treated with pilocarpine ip combined saline into the LPBN.ConclusionThe results suggest that strong cholinergic‐induced sodium intake arises when the inhibitory mechanisms are deactivated with noradrenaline injected into the LPBN combined with the blockade of pressor responses with ip prazosin.
Effects of Korean red ginseng on cyclophosphamide‐induced immunosuppression: comparative effects of 6‐year and 4‐year old Korean red ginseng
Authors: Hyun Sun Hee 
Published: June 2021

In this study, the protective effects of Korean red ginseng (KRG) against cyclophosphamide (CY)‐induced immunosuppression were investigated in animal models. Male BALB/c mice were divided into 6 groups: Normal and CY‐control groups were fed normal diet and the four test groups received modified diets containing 5 or 10% of 4‐year old or 6‐year old KRG powder for 4 weeks. In the subtype and NK cell activity assay, CY was given intraperitoneally in a single dose of 50 mg/kg three days before sacrifice. For the T‐dependent antibody response, CY was given intraperitoneally in a single dose of 50 mg/kg five days before sacrifice and mice were immunized with sheep red blood cells (SRBCs) intraperitoneally in the next day.CY, as reported, showed suppressed effects on body weights, organ weights, splenic lymphocyte subpopulation (total T cells, CD4+ T cells, CD8+ T cells, macrophages and B cells), antibody‐forming cells to SRBC and NK cell activity in these animals. The administration of KRG powder elevated the depressed relative weights of thymus and spleen and increased the number of splenic lymphocyte subpopulation, anti‐SRBC producing cells that were remarkably decreased by the treatment of CY. 6‐year old KRG powder showed more potent effect than 4‐year old KRG in enhancing immune function in the CY‐immunosuppressed mice. These results suggest that 6‐year old KRG is more potent in stimulating immunity in immunosupressed condition than 4‐year old KRG.
Activation of Protease‐activated receptor −3 signals independently to phosphorylate endothelial nitric oxide synthase in human endothelial cells
Authors: Tillery Lakeisha C. , Epperson Tenille , Mantey Jane , Motley Evangeline 
Published: June 2021

Protease‐activated receptor‐3 (PAR‐3) is widely recognized as a non‐signaling elusive member of a G protein‐coupled receptor family known to regulate the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathway via phosphorylation of its regulatory sites. Failure of the eNOS/NO pathway leads to endothelial dysfunction, a precursor to cellular induced hypertension. Using human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) as a model for human endothelium, we demonstrated that PAR‐3 is highly co‐expressed with PAR‐1 and ‐2 and can be activated using a synthetic peptide, SFNGGP‐NH2. We hypothesize that PAR‐3 can signal independently of PAR‐1 and ‐2 to regulate eNOS. Analysis using eNOS specific antibodies showed that 50uM of SFNGGP lead to the phosphorylation of the positive site of eNOS at ‐Ser1177 and the negative site ‐Thr495 in a time‐dependent manner in both cell lines. Human endothelial cells pretreated with 10uM of SCH79797, a selective PAR‐1 inhibitor, and then stimulated with SFNGGP; we observed an increase in phosphorylation at both eNOS regulatory sites. Using siRNA, transient knock‐down of PAR‐1 confirms PAR‐3 independent signaling potential. Our data suggests that PAR‐3 is able to regulate eNOS/NO signaling via site specific phosphorylation that is independent of PAR‐1 activation. Cardiovascular disease is the leading cause of death among Americans, where hypertension can be a silent aggressor. Studying the signaling pathways responsible for eNOS‐induced NO production will lead to a better understanding of endothelial dysfunction in cardiovascular diseases.NIH‐NIGMS‐SCORE and Porter Physiology Developmental Fellowship
Differences in resting metabolic rate and physical activity patterns in lean and overweight/obese pregnant women
Authors: Ruebel Meghan Lynne , Shankar Kartik , Badger Thomas , Andres Aline 
Published: June 2021

Energy requirements vary during pregnancy due to changes in physical activity (PA) and maternal fat stores. This study measured resting metabolic rate (RMR) and PA patterns in healthy lean and overweight/obese (OW) pregnant women. RMR was measured using indirect calorimetry (MOXUS), activity patterns were estimated by omnidirectional accelerometers (Actical®) and body composition was measured using air displacement plethysmography (BodPod®). Nineteen pregnant women including 12 lean (BMI 18.5–24.9 kg/m2) and 7 OW (BMI 25–35 kg/m2) were assessed at 6–10, 12 and 24 weeks (wk) of gestation. Absolute RMR differed significantly between lean and OW women (1438 ± 49 vs. 1753 ± 62 kcal/day, p<0.05) at 6–10 wk. Moreover, when adjusted for weight, RMR (kcal/kg/d) differed (p<0.05) throughout pregnancy for lean and OW women (23 ± 1 vs. 21 ± 1, 24 ± 1 vs. 20 ± 1, 22 ± 1 vs. 19 ± 1 at 6–10, 12 or 24 wk, respectively). RMR was also positively correlated with fat mass and fat free mass in both groups (r=0.77, and r= 0.52, respectively, p<0.05). Although not significant, lean women spent ~50 more minutes in moderate to vigorous and ~150 less minutes in sedentary time compared to the OW over the 24 wk. In conclusion, OW women had lower RMR (kcal/kg/d) and decreased PA compared to lean women, suggesting a greater risk of excessive gestational weight gain and post partum weight retention. USDA‐ARS CRIS# 6251‐51000‐005‐03S.Grant Funding Source : USDA‐ARS CRIS# 6251‐51000‐005‐03S
Combined Effect of Flow‐Mediated Shear Stress and Resveratrol on Sirt1/PGC‐1α Pathway in Vascular Endothelial Cells.
Authors: Kim Ji Seok , Kim Boa , Park Joon-Young 
Published: June 2021

The concept of enhancing structural integrity of mitochondria has emerged as a novel protective mechanism against CVD. Flow‐mediated laminar shear stress (LSS) and resveratrol (RSV) have vasoprotective effects, in part, by promoting mitochondrial biogenesis through Sirt1/PGC‐1α pathway.ObjectiveThe purpose of this study was to test a hypothesis that combined treatment of the two effective stimulators would have synergistic effect on the activation of Sirt1/PGC‐1α pathway in endothelial cells (ECs).MethodsHUVECs were exposed to either high LSS (h‐flow, exercise‐mimic, 20 dyne/cm2), RSV (20 μM), or h‐flow + RSV conditions for 12 h. For the h‐flow conditions, cells were further exposed to low LSS (l‐flow, postexercise recovery‐mimic, 5 dyne/cm2) for 24 h.ResultsRSV treatment increased Sirt1 and PGC‐1α expression levels in a dose‐and time‐dependent fashion. We observed that the Sirt1 protein expression level was further increased under h‐flow + RSV condition (P < .05). Moreover, h‐flow resulted in 10‐fold increase in PGC‐1α expression level during l‐flow (P < .05). However, there was no additive effect of RSV on PGC‐1α expression level at any shear conditions.ConclusionThe current preliminary data suggests that, although the combined RSV and h‐flow treatment has a synergistic effect on Sirt1 expression, h‐flow may override the effect of RSV with respect to the mitochondrial biogenesis in ECs.
Effects of physical training on neuronal hypothalamic activation induced by exercise
Authors: Santiago Henrique Pereira , Leite Laura Hora Rios , de Andrade Lima Paulo Marcelo , Rodovalho Gisele Vieira , Szawka Raphael Escorsim , Coimbra Cândido Celso 
Published: June 2021

We assessed whether the effects of physical training on heat balance are followed by hypothalamic activation induced by exercise. After physical training (8 weeks), trained (T) and untrained (UT) Wistar rats were submitted to graded running until fatigue while body (Tb) and tail (Ttail) temperatures were recorded. Workload (W), body heating rate (BHR), heat storage (HS) and Tb threshold for tail vasodilation (TTbV) were determined. Afterwards, c‐Fos immunohistochemistry was conducted in paraventricular nucleus (PVN), medial preoptic nucleus (MPO) and median preoptic nucleus (MnPO). T animals had a 110% increase in W (p < 0.01), however, animals from both groups had similar increases in Tb and Ttail during exercise. A reduction of 0.6°C in TTbV was shown by T animals (p < 0.01), being possibly responsible for the lower BHR (0.019 ± 0.002 °C.min‐1, T vs 0.030 ± 0.005 °C, UT, p < 0.05) and ratio between HS and W (18.18 ± 1.65 cal/Kgm, T vs 31.38 ± 5.35 cal/Kgm, UT, p < 0.05). Physical training increased by 112%, 90% and 65% neuronal activation in the PVN, MPO and MnPO after running, respectively (p < 0.01), which was directly associated with W (PVN: r = 0.97; MPO: r = 0.86; MnPO: r = 0.77, p < 0.05). The data indicate that physical training enhances neuronal activation induced by exercise in these nuclei, related with improvement of exercise performance and probably with heat loss enhancement.Supported by: CNPq, FAPEMIG and CAPES.
Presence of VDR and CYP27B1 in mouse C2C12 cells and skeletal muscle reveal the action of 25(OH)D3 on suppression of myoblast proliferation
Authors: Srikuea Ratchakrit , Zhang Xiping , McCarthy John J. , Esser Karyn A. , Park-Sarge Ok-Kyong 
Published: June 2021

1α,25(OH)2D3, an active form of vitamin D3 was demonstrated to regulate myoblast proliferation via its nuclear vitamin D receptor (VDR). Local production of 1α,25(OH)2D3 was reported in the cells that express VDR and CYP27B1, the latter is used to convert 25(OH)D3 to 1α,25(OH)2D3. However, whether skeletal muscle expresses CYP27B1 and 25(OH)D3 can be used as a precursor for the local synthesis of 1α,25(OH)2D3 in skeletal muscle and regulate muscle cell functions are currently unknown. In this study, we investigated 1) VDR and CYP27B1 mRNA transcripts in C2C12 cells (mouse muscle cell line) and skeletal muscle tissue 2) the expression of VDR and CYP27B1 protein in C2C12 cells 3) the effect of 25(OH)D3 on C2C12 cell proliferation. Here, we demonstrated that C2C12 cells and skeletal muscle expressed VDR and CYP27B1 mRNA transcripts. Both genes were significantly up‐regulated at the mRNA level after skeletal muscle was overloaded. Nuclear VDR and mitochondrial CYP27B1 were expressed in C2C12 myoblasts but not myotubes. 25(OH)D3 treatment increased nuclear VDR expression and inhibited C2C12 myoblast proliferation. This effect was abolished by CYP27B1 knockdown, suggesting CYP27B1 is required for 25(OH)D3 action in myoblasts. Taken together, the presence of VDR and CYP27B1 in C2C12 cells and skeletal muscle revealed the possible contribution of 25(OH)D3 on the regulation of skeletal muscle function, in part on controlling of muscle cell proliferation.This work was supported by NIH R01AR45617 to KAE and PGY funds to OKPS
Regulation of skeletal muscle oxidative phenotype by classical NF‐κB signalling
Authors: Remels Alexander , Gosker Harry , Schols Annemie , Langen Ramon 
Published: June 2021

Molecular mechanisms underlying loss of muscle oxidative phenotype (OXPHEN: intrinsic features determining fatigue resistance and capacity for substrate oxidation) in diseases associated with chronic systemic inflammation are unclear. In C2C12 myotubes, TNF‐α reduced protein and mRNA levels of myosin heavy chain (MyHC) slow and oxidative phosphorylation (OXPHOS) complex (I‐III) subunits. These effects of TNF‐α were blocked when classical NF‐κB signalling was genetically abrogated (C2C12‐IκBα‐SR). Accordingly, TNF‐α‐induced reductions in mRNA levels of the key OXPHEN regulators PGC‐ 1α and mitochondrial transcription factor A (Tfam) were attenuated in C2C12‐IκBα‐SR myotubes. Also, TNF‐α reduced mitochondrial fission (MTP18) and fusion (mfn‐2) mRNA expression in a classical NF‐κB‐dependent manner. In analogy, IL‐ 1β or over‐expression of P65/RelA or a constitutive active form of IKK‐β (key constituents of classical NF‐κB signalling) significantly decreased Tfam promoter trans‐activation as well as nuclear respiratory factor 1 (NRF‐1) transcriptional activity. This data shows that classical NF‐κB activation is both sufficient and required for TNF‐α‐induced impairment of skeletal muscle OXPHEN, which is relevant for several pathological conditions characterized by systemic inflammation and muscle dysfunction.This study was supported by the Netherlands Asthma Foundation (3.2.09.068).
Doxorubicin impairs skeletal muscle mitochondrial respiratory capacity in skeletal muscle
Authors: Gilliam Laura A. A. , Fisher-Wellman Kelsey H. , Lin Chien-Te , Maples Jill M. , Neufer P. Darrell 
Published: June 2021

Debilitating muscle weakness and fatigue are common side effects of chemotherapy in cancer patients, limiting recovery and increasing morbidity. Our previous work shows that doxorubicin, a common chemotherapy drug, elevates reactive oxygen species (ROS) and decreases contractile force in skeletal muscle. As mitochondria represent a primary source of oxidant generation in muscle, we hypothesized that doxorubicin may compromise mitochondrial respiratory control and increase ROS production. 72 hrs following a single doxorubicin injection (20 mg/kg), maximal ADP‐stimulated O2 consumption was decreased during respiration supported by palmitoylcarnitine (PC) (−46 ± 26 %, p<0.05) and pyruvate/malate (−43 ± 21 %, p<0.05, n=6/group) in permeabilized fiber bundles (PmFB) from red gastrocnemius muscle. PmFB from doxorubicin treated animals also display increased rates of mitochondrial H2O2 emission with PC (23 ± 2 %) and 3‐phosphoglycerate (49 ± 2 %, p=0.1). Our data indicate that doxorubicin impairs both maximal State 3, and fatty‐acid‐supported respiration. In addition, doxorubicin promotes mitochondrial ROS generation, a potential underlying cause of doxorubicin‐induced muscle dysfunction.Supported by DK073488
Genioglossus motor unit properties in a rat model of sleep apnoea
Authors: O'Halloran Ken D. , Bradford Aidan , Jones James FX , Edge Deirdre 
Published: June 2021

Intermittent hypoxia elicits plasticity in sensory and motor pathways involved in the control of breathing with potentially adaptive and maladaptive consequences for respiratory homeostasis. Chronic intermittent hypoxia (CIH) is a major feature of sleep‐disordered breathing. We sought to test the hypothesis that CIH alters pharyngeal dilator muscle motor unit properties.Adult male Wistar rats were exposed to 20 cycles of normoxia and hypoxia (5% O2 at nadir; SaO2 ~ 80%) per hour, 8 hours a day for 7 days (CIH, N=5) or sham treatment (N=5). Following gas treatments, rats were anaesthetized (urethane 1.5g/kg i.p.) and genioglossus (GG) muscle single motor unit potentials were recorded during quiet basal breathing.During basal breathing, the amplitude and duration of GG motor units was significantly different in sham vs. CIH‐treated rats (313±32μV vs. 430±46μV (amplitude) and 5.0±0.4ms vs. 3.4±0.2ms (duration); mean±SEM, Student's t test, p=0.0415 and 0.0013 respectively). The most common firing frequency of individual units determined from auto correlograms was significantly decreased (53±6Hz vs. 37±3Hz, sham vs. CIH, p=0.0318).Our results indicate that CIH causes remodelling in the central respiratory motor network with potential consequences for the physiological control of upper airway patency.