bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute and Chronic Endothelial Responses to Home-based High Intensity Interval Training in Healthy Older Adults
Authors: Lapierre-Nguyen Stephanie , Kim Jin-Su , Soonhuae Chatchamarn , Sakarya Yasemin , Riesco Eléonor , Robinson Katherine , Brierley Victoria 
Published: May 2024

Advancing age is associated with endothelial dysfunction, a key early event in atherosclerosis development. Endurance exercise is recommended for cardiovascular disease prevention and some studies report endurance exercise training has beneficial effects on endothelial function in older adults. We have recently developed a supervised home-based exercise intervention using high intensity interval training on an all-extremity non-weight-bearing ergometer (HIIT-ANE). We tested the hypotheses that in healthy older adults: 1) endothelial function is improved in response to chronic HIIT-ANE, 2) the acute endothelial responses to HIIT-ANE are different in the trained and untrained states, and 3) the acute and chronic endothelial responses to HIIT-ANE are related. We assessed flow-mediated dilation (FMD), a measure of endothelial function, using brachial artery ultrasonography in twenty healthy sedentary older adults (age: 66±1, means ± SE; 11 postmenopausal women and 9 men). FMD was assessed: 1) in response to chronic HIIT-ANE (at baseline, after 8 weeks of normal lifestyle (control condition), and after 8 weeks of home-based HIIT-ANE) and 2) in response to a single session of HIIT-ANE (at pre-exercise, end of exercise and 1-hr and 24-hrs post-exercise), in the untrained and trained states. Following 8 weeks of HIIT-ANE, FMD was improved compared with baseline (3.39±0.30 vs. 4.18±0.46 %, P=0.005), but was not significantly changed from pre- to post-HIIT-ANE (3.68±0.44 vs. 4.18±0.46 %, P=0.3) or from baseline to post-control (3.39±0.30 vs. 3.68±0.44 %, P=0.4). In the untrained state, FMD was attenuated in response to a single bout of HIIT-ANE from pre- to 1-hr post-exercise (4.15±0.35 vs. 2.92±0.36 %, P=0.0004) and returned to pre-exercise level in 24-hrs post-exercise (4.15±0.35 vs. 3.98±0.40 %, P=1). In the trained state, the acute FMD response to HIIT-ANE was similar to the untrained state (P=0.6 for training state × time). The chronic change in FMD was inversely related with the acute change in FMD in the trained state (ρ=-0.70; p<0.001), but not in the untrained state (ρ=-0.12; P=0.6). Biological sex did not significantly influence the acute or chronic FMD responses to HIIT-ANE (P≥0.1). In healthy older adults: 1) FMD is improved following 8-weeks of home-based remotely supervised HIIT-ANE compared to baseline, 2) FMD is attenuated and normalized within 24 hours of a single session of HIIT-ANE, and 3) chronic changes in FMD are related to acute changes in FMD. This work was supported by the National Institute of Aging grant AG063143. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effects of high, sub-lethal doses of fentanyl on respiratory functions in adult female goats
Authors: Taylor Reiauna , Hodges Matthew R. , Neumueller Suzanne , DeSalvo John , Hilbert Grace , Forster Hubert 
Published: May 2024

Since 1999, the opioid epidemic in the United States has claimed more than 300,000 lives, and data from more recent years indicate annual increases exceeding 80,000 fatalities. Synthetic opioids like fentanyl contribute to these opioid-related deaths through multiple physiologic effects including Opioid-induced respiratory depression (OIRD), impairment of the alveolar to arterial oxygen gradient (A-a), and rigidity of upper airway and pump muscles causing airway dysfunction, or Wooden Chest Syndrome (WCS). We have previously shown (PMID: 37885800) that sub-lethal doses of fentanyl (25-125 μg/kg; IV) cause in healthy adult goats a transient time and dose dependent effect on breathing frequency and tidal volume, WCS and A-a which varied greatly between goats. We hypothesize that high dose fentanyl will exacerbate the effects seen in sub-lethal doses in both a time and dose-dependent manner. Adult female goats (n=3) were surgically instrumented with electromyographic (EMG) wires in both the airway (genioglossus and thyropharyngeal) and respiratory pump muscles (diaphragm, transverse abdominus and diaphragm) and the carotid arteries were relocated to a subcutaneous location. Goats were allowed 2 weeks for recovery before the onset of studies. Arterial blood samples were obtained through carotid catheters and fentanyl injections were made through acute placement of jugular venous catheters. Following a 30-minute control period, we injected saline (vehicle) or high-dose fentanyl (250-500μg/kg). In a time dependent manner, high doses of IV fentanyl injections decreased breathing frequency (FB), increased expiratory time (TE) and increased tidal volume (VT). Arterial oxygen (PaO2) decreased substantially (~35 mmHg; and arterial CO2 (PaCO2) increased to as high as 70mmHg. From about 15 to 90 minutes after fentanyl injections, the overall effect on breathing and respiratory muscle activity was consistent with a stimulatory effect of fentanyl. These data suggest high dose fentanyl increases OIRD and exacerbate life-threatening effects that cause ventilatory suppression, hypoxemia, and hypercapnia. Funded by NIH DA050571. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The Role of Interleukin-6 in Regulating Glomerular Filtration Rate during Angiotensin II and High Salt Conditions
Authors: Hatcher Mark , Duan Rong , Lee Dexter 
Published: May 2024

Previous results demonstrate that interleukin-6 (IL-6) increases mean arterial pressure (MAP) during Angiotensin II (Ang II)-salt hypertension. In addition, albumin excretion was lower in IL-6 knockout mice (KO) when compared to wild-type (WT). This study investigated the role of IL-6 on regulating glomerular filtration rate (GFR), renal plasma flow (RPF) and MAP in WT and IL-6 KO mice treated with a slow pressor dose of Ang II (200 ng/kg/min) +/- 6% high-salt (HS) diet. Male C57BL6 and IL-6 KO mice (12 weeks old) were treated with Ang II +/- 6% HS diet for 12 – 14 days. Mean arterial pressure, RPF and GFR were measured in anesthetized mice. MAP was 130 ± 7 mmHg and 91 ± 4 mmHg in control WT and IL-6 KO mice, respectively. Ang II treatment increased MAP in WT (153 ± 5 mmHg) and no change in IL-6 KO (83 ± 4 mmHg) mice. Ang II + 6% HS increased MAP to 150 ± 11 mmHg in WT and 93 ± 4 mmHg in IL-6 KO mice. Baseline RPF was 1822 ± 229 and 1912 ± 402 ml/min/g in control WT and IL-6 KO mice, respectively. Ang II treatment increased RPF in WT (3156 ± 753 ml/min/g), while lowering RPF in IL-6 KO (1648 ± 422 ml/min/g) mice. RPF during Ang II + 6% HS treatment was decreased in WT (1095 ± 305 ml/min/g) and IL-6 KO (1133 ml/min/g) mice. GFR was 756 ± ml/min/g and 788 ± ml/min/g in control WT and IL-6 KO mice, respectively. Ang II increased GFR in WT (1009 ± 63 ml/min/g) and no change in IL-6 KO (756 ± 23 ml/min/g). Ang II + 6% HS increased GFR in WT (1095 ± 146 ml/min/g) and no change in GFR of IL-6 KO (540 ± 207 ml/min/g) mice. Our results suggest that IL-6 reduces MAP during baseline, Ang II, and Ang II + 6% HS. The absence of IL-6 prevented increases in MAP, RPF and GFR during Ang II treatment. Our data also suggest that IL-6 contributes to increased MAP and GFR during Ang II + 6% HS treatment. K01HL092593-05. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Noninvasive focused ultrasound stimulation of the celiac-superior mesenteric ganglion complex regulates inflammation in murine endotoxemia
Authors: Palandira Santhoshi Poonacha , Falvey Aidan , Brines Michael , Chavan Sangeeta S. , Tracey Kevin J. , A. Pavlov Valentin 
Published: May 2024

The nervous system has an important role in the regulation of cytokines and inflammation ( Nature, 2002). The celiac-superior mesenteric ganglion complex (CSMGC) is an important component of the vagus nerve based inflammatory reflex, which controls inflammation ( Nat Neuroscience 2017). In addition to receiving cholinergic innervations from the efferent vagus nerve, the CSMGC is innervated by preganglionic sympathetic splanchnic nerves, which also are involved in the inflammatory regulation. Both neuronal types - vagal and preganglionic sympathetic - interact with catecholaminergic neurons, which reside in this ganglionic complex and innervate the liver, spleen, and other abdominal organs. Despite being a prominent locus of neuronal interactions, the possibilities of directly targeting the CSMGC to regulate cytokine responses and inflammation remains unexplored. To provide insight, we subjected the CSMGC in mice to focused ultrasound stimulation (FUS) - a non-invasive approach, which has been increasingly utilized in neuromodulation. We used ultrasound imaging and doppler to localise the complex in anesthetized 10–14-week-old male C57BL/6J mice. To perform stimulation, the FUS transducer was placed on the abdominal surface over the CSMGC and FUS (1.1MHz and 200mV per pulse, 150 burst cycles, 500μs burst period) or sham stimulation was delivered for 2 mins or 5 mins. Five mins post FUS, mice were injected with lipopolysaccharide (endotoxin, 0.25mg/kg, i.p.) and euthanized after 90 mins. Blood and liver were collected and processed for cytokine analysis. Compared to sham stimulation, FUS of the CSMGC for 5mins (n=11,12/group) significantly decreased serum TNF levels (1,875 ± 750 pg/ml vs 672.9 ± 335 pg/ml, P< 0.0001) and hepatic TNF levels (27.8 ± 8.6 pg/mg vs 16.0 ± 7.1 pg/mg, P= 0.0018) in endotoxemic mice. In contrast, FUS of CSMGC for 2 mins (n=15/group) did not significantly alter serum TNF levels (1,458 ± 599.9 pg/ml vs 1,120 ± 332.5 pg/ml, P=0.1607). These results demonstrate the anti-inflammatory effcacy of noninvasive FUS of the CSMGC. Our findings also identify the CSMGC as an easily targetable new therapeutic site for controlling systemic and hepatic inflammation with a potential for clinical translation. This work was partially supported by NIGMS. R01GM128008. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Increased Farnesoid X Receptor agonism in frontal cortex is associated with neuronal loss in a pig model of pediatric non-alcoholic fatty liver disease
Authors: Maj Magdalena , Burrin Douglas , Manjarin Rodrigo 
Published: May 2024

Clinical studies suggest a link between non-alcoholic fatty liver disease (NAFLD) and neurodegeneration, but the mechanisms connecting both pathologies remain unknown. Rodent models of liver failure have shown neurological decline to be associated with increased bile acid (BA) levels and BA-activated farnesoid X receptor (FXR) signaling in the brain, which may disrupt brain’s cholesterol metabolism and promote neuronal death. We have previously established a pediatric animal model of NAFLD by feeding juvenile Iberian pigs a diet high in fat and fructose (HFF) for 10 weeks. The aim of this study was to determine whether BAs and FXR gene expression were increased in the frontal cortex (FC) of NAFLD pigs, and whether these changes were associated with neuronal loss. Eighteen 15-day-old Iberian pigs were assigned to receive for 10 weeks either a control (CON) or a HFF diet. FC was collected for immunohistochemistry, metabolomics, and transcriptomics analyses. Functional enrichment analyses were performed on differentially expressed genes to identify Gene Ontology (GO) terms using the Database for Annotation, Visualization, and Integrated Discovery. All HFF-fed pigs developed NAFLD. Immunostaining of mature neurons with NeuN was lower in FC of HFF compared with CON (P ≤ 0.05), whereas total BA levels increased (P ≤ 0.05) in FC of HFF-fed pigs. Brain levels of cholic and conjugated deoxycholic acids, which are FXR agonists, increased ( P ≤ 0.05) in HFF compared with CON. Conversely, tauroursodeoxycholic acid, which has strong FXR-antagonistic effect and has been shown to exert neuroprotective functions, was decreased (P ≤ 0.001) in HFF and was positively correlated with NeuN staining intensity (R2 = 0.623; P ≤ 0.001). Expression of FC genes encoding FXR, BA synthetic enzymes sterol 24- and 27-hydroxylases, and BA transporters Na+-taurocholate cotransporting polypeptide, organic anion transporting polypeptide, and organic solute transporters alpha and beta did not differ between groups. GO terms associated with Wnt/β-catenin pathway, which promotes neuronal survival and neurogenesis, were downregulated in HFF-fed pigs ( P ≤ 0.05), whereas mitochondrial respiratory chain complex and mitochondrion increased in HFF compared with CON ( P ≤ 0.01). In conclusion, increased BA levels and FXR agonism in frontal cortex of NAFLD pigs was associated with dysregulated Wnt/β-catenin signaling pathway and neuronal loss. California State University Agriculture Research Institute (grants 58873 and 58913), California Polytechnic State University internal funding programs Baker/Koob, RSCA, Frost, BiOWiSH Technologies, Hilmar Ingredients, and Acorn Seekers. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Cross Sex Steroid Therapy and Baseline Cardiac Function in a Rodent Model of Gender Affrming Hormone Therapy in the Male Rat
Authors: Crudup Breland F , Mallette Jordan H , Nabors Harley S , Willis Alex T , Cockrell Kathy L , da Silva Alexandre A , L Yanes Cardozo Licy 
Published: May 2024

Transgender females (TGF) are individuals who are born biologically male, but identify as female. Gender-Affrming Hormone Therapy (GAHT), consisting of 17β-Estradiol (E2) supplementation with androgen suppression [i.e. castration (CTX)], is used in TGFs to match their physical characteristics with their perceived gender. Previously, we reported that E2+CTX in the normotensive male Sprague-Dawley (SD) rat is associated with a significant increase in E2 and decrease in testosterone, body weight, and lean mass. Whether GAHT enhances cardiac morbidity and mortality in the transgender population on GAHT relative to cisgender individuals is still unclear. Moreover, the sustained effect of high E2 coupled to androgen suppression in male rats on their cardiac morphology and function is unknown. Thus, this study tested the hypothesis that GAHT in the adult male SD rat is associated with impaired cardiac function under baseline conditions. Methods: Adult male SDs (13 weeks of age) were randomly assigned to either: Control or E2+CTX therapy (E2 at 5 mg/day, pellet sc, replaced every 3 weeks, with CTX performed at 15 weeks of age) (n=8/grp). Baseline cardiac function was measured via echocardiogram (VEVO 3100), body composition via EchoMRI. Results: at 28 weeks of age, total lean mass and body weight were significantly decreased in the E2+CTX group, as previously observed; total fat mass did not differ between groups. Heart rate was significantly decreased; yet, other indices of cardiac function were not altered at baseline. Although no major differences in baseline cardiac function were observed, the long-term impact of GAHT on CV health and the ability of the heart to respond to secondary challenges are unknown. This study is ongoing and further studies will determine the ability of the heart to recover from secondary insults in order to determine if GAHT in males is associated with increased CV risk. [Formula: see text] Funding sources: HL143459, P20-GM-104357, P20-GM121334, T32-HL105324. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Skeletal muscle ULK1 and ULK2 modulate protein synthesis impacting fiber size
Authors: Son Wangkuk , Fuqua Jordan , Harris Matthew P. , Allen Ryan J. , Kronemberger Ana , De Sousa Luis G , Bodine Sue C 
Published: May 2024

Maintenance of skeletal muscle homeostasis is largely influenced by the processes of protein synthesis and degradation. However, the regulation of these processes remains incompletely understood particularly in a tissue or cell type-specific manner. We have previously demonstrated that Unc-51 like autophagy activating kinases 1 and 2 (Ulk1/2) are among the top 5 mostly enriched putative autophagy genes in skeletal muscle when compared to >90 other mouse tissues and cell lines (Fuqua et al., FASEB J, 2019). However, because protein kinases commonly have several downstream targets, here we hypothesized that skeletal muscle ULK1 and ULK2 redundantly modulate other important cellular processes. To begin to address this question, we generated mice with skeletal muscle-specific knockout of ULK1 and ULK2 (i.e., ULK1/2 skmDKO) and studied those at different ages. Muscle basal autophagy flux was impaired in ULK1/2 skmDKO mice. However, contrary to other models of autophagy impairment, which commonly leads to muscle atrophy, adult ULK1/2 skmDKO mice had increased muscle size (15-25%, P≤0.01). Hypertrophy occurred in all fiber types (6-20% increase in fiber diameter, P≤0.05) and in response to an acute (4-week) deficiency of ULK1/2 (via electroporations of plasmids encoding ULK1/2miR), where TA fiber diameter increased by 9% (p<0.05). Further studies using D2O labeling and cellular fractionation revealed that ULK1/2 skmDKO mice have increased myofibrillar protein synthesis rates (~5%/day, p<0.05). Examination of the molecular mechanisms involved suggests that ULK1/2 skmDKO mice have enhanced mTORC1-dependent signaling, particularly in the fed state. Altogether, our findings reveal for the first time that ULK1 and ULK2 collectively stimulate protein degradation and inhibit protein synthesis in skeletal muscle potentially impacting muscle mass and function in conditions of muscle atrophy and hypertrophy. Supported by the University of Iowa Fraternal Order of Eagles Diabetes Research Center (UIowa FOEDRC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effect of Adipose Biopsy Technique on Inflammatory Markers in Adipose Tissue
Authors: Brandt Anna , Lynch Colleen , Robbins Ethan , Chambers Toby , Trappe Todd , Trappe Scott 
Published: May 2024

Objectives: The purpose of this study was to compare adipose tissue (AT) biomarkers obtained from the Bergström and Mercedes biopsy techniques in healthy, recreationally active adults. Hypotheses: There would be no difference in expression of inflammatory and adipokine genes of interest between techniques. There would be no difference in the concentration of inflammatory cytokine levels between techniques. Methods: Basal abdominal subcutaneous AT was obtained from 12 (8M, 4F; 28±4 y; 86±8 kg; BMI 26.8±2.9 kg/m2; body fat 29±8%; VO2max 3.4±0.7 L/min) healthy, recreationally active adults (i.e., regular aerobic and/or resistance exercise 3-5 days/wk) on contralateral sides of the umbilicus via Bergström and Mercedes biopsy techniques. Inflammatory and adipokine gene expression levels (IL1β, IL6, IL8, IL10, TNFα, ADIPOQ, LEPD) were measured in AT (n=8) via qPCR. Inflammatory cytokine concentrations (GM-CSF, IFNγ, IL1β, IL2, IL5, IL6, IL8, IL12p70, IL17A, IL23, TNFα, IL4, IL10, IL13) were measured in AT (n=11) via high sensitivity discovery assay. Results: There were no differences in inflammatory nor adipokine gene expression between AT biopsy techniques (P>0.05). Of the measurable cytokines (GM-CSF, IFNγ, IL8, IL17A, IL13), there were no differences between Bergström and Mercedes AT (P>0.05). Average tissue yield for the Mercedes biopsy was greater than the Bergström biopsy (1007±625 mg vs. 291±83 mg, respectively; p<0.05). Conclusions: The analyses performed in this study suggest AT collected from Bergström and Mercedes techniques provide high-quality RNA (RNA integrity numbers >7.0) and protein with comparable basal transcriptional and translational profiles. Both techniques may be utilized in the collection of AT; however, research questions may impact the technique chosen as the Mercedes biopsy technique obtains larger tissue yields whereas the Bergström technique may allow for an increased number of biopsies due to the smaller abdominal area impacted. This research was supported by the Human Bioenergetics program at Ball State University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Mesenchymal Stem Cells improve phenotype of induced pluripotent stem cell (iPSC)-derived cardiomyocytes in Hypoplastic Left Heart Syndrome
Authors: Liang Huan-Ling , Anfinson Melissa , Mahnke Donna , Pereckas Michaela , Pan Amy , Tefft Brandon , Lincoln Joy 
Published: May 2024

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). We previously demonstrated that genetic variants in the alpha myosin heavy chain (MYH6) gene are significantly associated with HLHS as well as poor outcomes in patients. Additionally, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carrying an MYH6-R443P head domain variant demonstrated an impaired CM phenotype including dysmorphic sarcomere structure, altered contractility, and upregulated MYH7 expression. Mesenchymal stem cells (MSCs) and their secretome are currently being explored as a potential therapeutic for cardiac injury. In this study, a possible treatment strategy for iPSC-CMs with a MYH6 tail domain variant was examined through investigation of co-culturing umbilical cord tissue derived MSCs from a healthy newborn. iPSC-CMs from an unaffected family member were included as a normal control to compare cellular RNA and protein changes observed in the MYH6-E1584K line. The MYH6-E1584K variant line demonstrated significant upregulation of sarcomere, calcium channel, and inflammation/immune related gene expression in both mRNA and protein levels. Co-culturing with MSCs rescued expression of several genes and was confirmed through label free proteomic analysis. Co-culturing iPSC-CMs with MSCs also significantly improved contraction (contraction maximum displacement and velocity) in MYH6-E1584K iPSC-CMs. Finally, measurements of microRNA, cytokines, and exosomes secreted into cultured media indicated significant changes. This study suggests that MSC secreted factors improve CM expression and function and may elucidate a new mechanistic target for patients with HLHS. AHW/HHI Innovation Pilot Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.