bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light physical activity improves lower limb perfusion asymmetries in older sedentary adults — an exploratory study
Authors: Monteiro Rodrigues Luis , Florindo Margarida 
Published: May 2024

Perfusion asymmetries between lower limbs are common even in healthy young individuals, although their physiological significance is unknown. Even in the absence of vascular disease, ageing is among the determinants that seem to accentuate those differences. While it is known that physical activity affects vascular hemodynamics, its specific impact on perfusion asymmetries in healthy elderly individuals is still unclear. This study aimed to identify vascular asymmetries and their variations after a regular program of light exercise in older individuals with age-related comorbidities in the absence of peripheral vascular disease (PVD). Ten participants, mean age 62.4 ± 5.6 years old, were selected following specific criteria. Participants were mostly sedentary, combining one or more common morbidities for this age group — in particular hypertension, overweight and / or diabetes (T2D). Exclusion criteria were an abnormal Ankle-Brachial Index assessed in a standing position at rest and evidence of compromised mobility. All procedures respected the principles of good clinical practice, being previously submitted and approved by the institutional Ethical Commission. Lower limb perfusion was assessed in both feet (anteromedial region) at two time points — day zero (D0) and thirty days later (D30) — using two optical-based technologies — Laser Doppler Flowmetry (LDF) and Polarized Spectroscopy (PSp). These two technologies measure at different depths, with LDF providing deeper tissue readings. During this evaluation period, participants underwent a daily structured program of light exercises based on the FITT principles (F, frequency; I, intensity; T, time and T, type of activity/activity performance) centred in the lower limb perfusion. The group revealed significant asymmetries at D0, where the right foot consistently showed higher values with both technologies correlating positively. At D30, LDF values increased by 57.5% in both feet, meaning that asymmetries disappeared. No significant changes were observed with PSp. Basic cardiovascular functions such as blood pressure and mean arterial pressure were also evaluated, showing significant decreases in systolic pressure and mean arterial pressure. These encouraging results suggest that regular physical activity, even if light in intensity and duration, improves overall hemodynamics and specifically raises perfusion in the lower limbs. These findings should be further explored with the aimof prevention and treatment of PVD. This research was financed by national funds through FCT - Foundation for Science and Technology, I.P. (Portugal), under the [UIDB/04567/2020] and [UIDP/ 04567/2020] programs. 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.
TRIM Enhances Dystrophic Muscle Function 70 Days Post Treatment
Authors: Kendra Jacob , Naman Alexandra , Brow Richard , Segal Steven , Morton Aaron 
Published: May 2024

Background: Duchenne Muscular Dystrophy (DMD) is associated with limb muscle dysfunction caused by progressive weakness and degeneration of skeletal muscle. Current FDA-approved therapeutic strategies are less effective than originally hoped. Our alternative approach was to develop a novel biomaterial, Time Release Ion Matrix (TRIM), shown to release angiogenic ions and enhance muscle structure and function at 14 days post injection (dpi) in dystrophic (D2. mdx) mice. However, the long-term effects of TRIM are unknown. Hypothesis: At 70 days post injection in D2. mdx mice TRIM will: 1) enhance isometric force and myofiber cross-sectional area (CSA) of the tibialis anterior (TA) muscle; and 2) promote vascular endothelial growth factor (VEGF) availability and muscle vascularity. Methods: The right and left TA of adult male D2. mdx mice (n=6-7, age 5 months) were injected with saline alone (control) or 250 μg of TRIM suspended in saline. At 70 dpi, the left TA was isolated for in situ muscle force measurements and histological analysis; the right TA was frozen for biochemical analysis. Muscle cross-sections were immunostained for laminin (myofiber borders), DAPI (nuclei), and CD31 (endothelial cells). An ELISA for VEGF was performed on homogenates of frozen muscles. Results: TA’s injected with TRIM increased peak isometric force (means ± SE: TRIM 70.9 ± 1.8 g; Saline, 65.9 ± 1.1 g; P= 0.04). TRIM-treated TA’s had a 2.2-fold increase in relative frequency of myofibers >1000 μm2 (TRIM, 31.8 ± 3.7%; Saline, 14.4 ± 1.9%; P= 0.001), and reduced the frequency of myofibers <400 μm2 by 32% (TRIM, 38.6% ± 2.8; Saline, 56.5% ± 3.5; P= 0.001). DAPI staining revealed a 50% increase in central myonuclei indicative of regenerated myofibers (TRIM, 30.2 ± 1.7%; Saline, 20.2 ± 1.3%; P=0.0006). Microvessel area (CD31 staining; μm2) was 2.1-fold greater in treated TA’s (TRIM, 135.6 ± 8.7 μm2; Saline, 63.6 ± 4.5 μm2; P=0.0001). In muscle homogenates, TRIM increased [VEGF] (TRIM, 139 ± 10%; Saline, 100 ± 6%; P= 0.009) Conclusion: Results support the hypothesis that 70 days following injection of TRIM into the TA of dystrophic mice, muscle force and myofiber CSA are enhanced. Moreover, TRIM enhances VEGF with increased vascularity, suggesting that the angiogenic effects of TRIM complement those on myogenesis and contractile function towards restoring muscle structure and function in DMD. University of Missouri Coulter Biomedical Accelerator (SSS), Texas A&M Department of Kinesiology and Sport Management (ABM). 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 Derived Cells from Old Human Donors Show Increased Mitochondrial Lipid Peroxidation and Reduced Mitochondrial Function
Authors: Arevalo Jose , Avalos Heidi , Brooks George , Vazquez-Medina Jose Pablo 
Published: May 2024

Skeletal muscle undergoes atrophy with age progression resulting in decreased mitochondrial function. Similarly, age-related increases in mitochondrial oxidant generation can promote mitochondrial oxidative damage, but the relationship between increased oxidant stress and mitochondrial function is not well understood. Here, we profiled changes in mitochondrial function and mitochondrial lipid peroxidation in intact primary skeletal muscle progenitor cells (myoblasts) derived from the Rectus abdominis muscle of healthy young (19.67 ± 1.70 years) and old (67.0 ± 1.41 years) humans. Using metabolic flux assays, we found that cells derived from young humans showed higher basal and maximal oxygen consumption rates compared to cells derived from old humans (basal: 22.67 ± 6.53 vs. 10.81 ± 5.69; maximal: 41.02 ± 15.20 vs. 17.33 ± 4.84 pmol/min/protein, p < 0.001). Similarly, cells derived from young humans also showed higher ATP production and spare respiratory capacity (ATP: 18.79 ± 5.17 vs. 9.15 ± 4.91; SRC: 18.35 ± 9.62 vs. 6.52 ± 3.42 pmol/min/protein, p < 0.001). In contrast, using live-cell fluorescence microscopy, MitoTracker red and the mitochondrial-target lipid peroxide probe MitoPeDPP, we found higher mitochondrial lipid peroxidation levels in cells derived from old than young humans ( p = 0.0007). We then evaluated whether peroxiredoxin 6 (Prdx6), an enzyme that repairs lipid peroxidation through its phospholipid glutathione peroxidase and phospholipase A2 activities, impacts mitochondrial function using CRISPR/Cas9-mediated knockouts of Prdx6 in C2C12 myoblasts and extracellular flux assays. Spare respiratory capacity was lower in cells with full Prdx6-KO than in cells transfected with non-target gRNAs (NT: 295.10 ± 18.59 vs. Prdx6-KO: 242.20 ± 17.93; p = 0.05). These results show that mitochondrial function decreases with age along with increases in mitochondrial lipid peroxidation in primary muscle cells derived from old humans. Similarly, these results show that the Prdx6 supports mitochondrial function. Overall, our data contributes to our understanding of the mechanistic drivers of age-related skeletal muscle mitochondrial dysfunction. NIGMS-R35GM146951 NIA-R01AG059715. 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.
Impact of exercise on uncoupling protein 1 and macrophage phenotype in mesenteric adipose tissue in an animal model of endometriosis
Authors: Cruz Myrella L. , Torres-Pirela James , Chompre Gladys , Vazquez-Ubides Ernesto , Rivera-Arce Luis A. , Appleyard Caroline B. 
Published: May 2024

Endometriosis is a gynecological disorder characterized by growth of endometrial tissue outside the uterine cavity, with symptoms which may include chronic pelvic pain and infertility resulting in a decreased quality of life. Previous studies in our laboratory demonstrated that endometriosis animals have increased mesenteric adipose tissue (MAT), inflammation, and growth of implanted endometrial vesicles which are decreased by voluntary exercise. The levels of Uncoupling Protein 1 (UCP-1), a mitochondrial protein, are known to be increased by exercise in rodents, promoting thermogenesis and decreasing inflammation. Exercise can also increase expression of peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily. When activated PPARγ polarizes the macrophages into an anti-inflammatory M2 state, which can stimulate white adipose tissue beiging. We hypothesized that voluntary wheel running exercise can increase UCP-1 and M2 macrophages, decreasing MAT and endometrial vesicle size. Aim: To assess the impact of voluntary exercise on UCP-1 expression and macrophage phenotype in MAT of an animal model of endometriosis. Methods: Endometriosis was induced by implanting uterine tissue on the intestinal mesentery of female Sprague Dawley rats while control group only received sutures (SHAM). Exercise rats had access to a running wheel after surgery (ENDO-EX or SHAM-EX), while non-exercised animals didn’t (ENDO and SHAM; n=10-11/group). After sixty days, animals were sacrificed, and MAT was collected to determine CD68, UCP-1 and PPARγ expression by immunofluorescence staining. Results: Vesicles from ENDO-EX animals exhibited significantly decreased average weight (p<0.01) and smaller average total area (p<0.01) compared with the ENDO group. Endometriosis animals showed increased mesenteric adipose tissue when compared to sham group (p<0.01), which was reduced by voluntary exercise (p<0.001). Macrophage infiltration, UCP-1 and PPARγ expression increased with exercise. Conclusions: Increased UCP-1 and anti-inflammatory M2 macrophages following exercise may result in browning of MAT which can have a role in reducing the development of vesicles in the endometriosis model. These findings suggest that exercise may be a potential complementary therapeutic strategy for managing endometriosis symptoms. This work was supported by R15AT009915, R16GM149365, T32GM144896, PRI MD Summer Program and Porter Physiology Development Fellowship. 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 Impact of Goode Health LLC Superfood Chocolate Blend Beverage on Peripheral Macro and Microvascular Function
Authors: Ortiz Alison , Kolade John O. , Perry Ken A. , Shah Prarthi J. , Brothers R. Matthew 
Published: May 2024

Cardiovascular disease (CVD) is the leading cause of death in the US and world-wide. The are many risk factors associated with elevated risk for and prevalence of CVD; however, it is well documented that reduced macro and microvascular function/health is a major contributing factor. The mechanisms are multifactorial however, reduced vasodilatory reactivity, secondary to elevated oxidative stress and/or inflammation contribute to elevated disease risk. Diets and/or interventions high in antioxidants, polyphenols, and/or anti-inflammatory properties reduce CVD and metabolic disease risk. Furthermore, this is mediated in part through improvements in vascular function. This study tested the hypothesis that 2-weeks of increased daily consumption of a beverage high in antioxidants, polyphenols, and anti-inflammatory properties would improve well-validated indices of peripheral macro and microvascular function in a cohort of Hispanic individuals. METHODS: Six Hispanic individuals (4 males; age: 42±14 yr.; BMI 32±7 kg/m2) participated. All measures were assessed before (pre) and following (post) 14-days of increased daily consumption of the Goode Health LLC Superfood Moroccan Chocolate Blend. During the intervention participants added the chocolate blend powder mix (~28 g) to 8 oz water twice daily. This beverage is high in healthy ingredients including plant-based proteins, prebiotic fiber, antioxidant polyphenols, and anti-inflammatory properties. Peripheral macro and microvascular function/health were assessed pre- and post-intervention as vasodilation in the brachial artery (flow mediated vasodilation; %FMD) and reactive hyperemia (peak mean forearm blood velocity (FBVmean)) in the forearm vasculature respectively following 5-min of forearm ischemia induced by suprasystolic cuff occlusion. RESULTS: Peripheral macrovascular function assessed as %FMD tended to be augmented following Goode Health LLC beverage consumption (Pre: 4.2±2.2 % vs. Post: 5.8±1.6 %, P=0.08). Whereas peripheral microvascular function assessed as peak FBVmean was augmented following the intervention (Pre: 70±17 cm·s−1 vs. Post: 78±20 cm·s−1, P=0.04) CONCLUSION: These preliminary data indicate a positive effect of Goode Health LLC Superfood Moroccan Chocolate Blend consumption on indices of peripheral macro and microvascular function/health. Future studies will continue to expand upon these findings in a larger cohort. Goode Health LLC. 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.
Myoglobin: A versatile age-old oxygen carrying hemoprotein and its emerging role in metabolite regulation in diverse tissues
Authors: Adepu Kiran Kumar , Anishkan Andriy , Adams Sean , Chintapalli Sree 
Published: May 2024

Myoglobin (Mb) is an age-old heme containing cytoplasmic protein primarily expressed in heart and skeletal muscles, which is capable of rapid release of O2 during the periods of hypoxia or anoxia. The canonical view of the primary physiological function of Mb is that it is a tissue oxygen (O2) storage protein supporting mitochondrial oxidative phosphorylation especially as the tissue O2 partial pressure ( pO2) drops and Mb increasingly offloads O2. For the past 50 years, many investigators are constantly exploring wide-range of physiological functions and metabolic regulation activities of Mb. Advanced genetic engineering tools and molecular techniques revealed important new insights and provided additional functions of Mb. However, accumulating evidence indicates that this paradigm is too narrow, especially in light of recent findings supporting plausible functions for Mb in lipid traffcking and sequestration, binding of small molecules such as lactate (LAC), pyruvate (PYR), glucose (GLU), polyamines, and glutathione (GSH), and “ectopic” expression in some types of cancer cells. Data from Mb knockout mice (Mb−/−) and biochemical models suggest additional metabolic roles for Mb, especially regulation of nitric oxide (NO) pools and modulation of thermogenic brown adipose tissue (BAT) bioenergetics and lipid storage phenotypes. From these and other findings in the literature over many decades, it may be contemplated that the primary role for Mb under most conditions for Mb besides delivering O2 in support of oxidative phosphorylation, but also serve as an O2-sensor that modulates intracellular O2- and NO-responsive molecular signaling pathways. This paradigm shift reflect a fundamental change in how oxidative metabolism and cell regulation are viewed in Mb-expressing cells such as skeletal muscle, heart, brown adipocytes, and select cancer cells. Herein, we present historic and emerging views related to the physiological roles for Mb, and working models illustrating the possible importance of interactions between Mb, gases, and small molecule metabolites in regulation of cell signaling and bioenergetics. USDA-ARS project 6026-51000-010-06S, Sturgis Foundation Grant AWD00054750 and ACRI-ABI Investigator Initiated Grant Award GR037175-4450S ABI. 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.
Hibernating at High Temperatures Increases Variability in Arousal Dynamics
Authors: Yankaway Raizel , van Breukelen Frank , Hindle Allyson G , Utz Jenifer 
Published: May 2024

In the winter, and presumably due to low resource availability, many mammals enter into a state of torpor wherein body temperature approaches that of ambient temperature and oxygen consumption rates can be as low as 1/100th of active rates. The canonical hibernation season is not static. Rather periods of torpor are interrupted by predictable periods of euthermy called interbout arousals which allows for a resetting of homeostatic processes. Here, we exposed golden-mantled ground squirrels to a range of ambient temperatures including high temperatures (4, 12, 20, 25, and 30°C). Preliminary analyses demonstrated higher temperatures resulted in decreased maximum rates of rewarming. On average, at 4°C ambient temperature rewarming was 0.14 °C per minute, while at 30°C ambient temperature the average maximum rate of rewarming was 0.012°C per minute. In addition, higher temperatures had a 2-fold higher relative time index which is defined as the time required to reach maximum rate of rewarming divided by the total arousal duration. Lastly, the interbout arousals increased 5-fold at warmer temperatures, lasting 12 hours at 4°C and 66 hours at 30°C. We interpret these data to suggest high temperature torpor leads to homeostatic issues wherein key processes are poorly coordinated. The result is an inherent increase in variability between individual squirrels and a loss of predictability of key hibernation aspects. NASA TRISH Department of Education NSF. 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 antagonism of thromboxane-prostanoid receptor on alcohol-associated liver disease
Authors: Ai Weilun , Casey Carol , Saraswathi Viswanathan 
Published: May 2024

Backgrounds: Alcohol-associated liver disease (ALD) is one of the leading causes of liver diseases. Thromboxane-prostanoid receptor (TP-R) is widely expressed in the liver and is activated by thromboxane A2 (TXA2). A previous study reported an increase in TP-R mRNA level in liver after ethanol feeding. Preclinical studies have documented that TP-R antagonists exert a protective effect against cardiovascular and liver diseases. In particular, TP-R antagonist is reported to attenuate ALD in rodents. However, the mechanism(s) by which antagonizing TP-R attenuates ALD remains unclear. Methods: Herein, we used the chronic plus binge ethanol feeding model. Briefly, male, C57BL/6 wild-type mice (8-week) were fed a Lieber-Decarli ethanol (5% v/v) diet (ET, n = 10) or isocaloric control diet (CON, n = 6) for ten days followed by a single binge administration of ethanol or maltose-dextrin via oral gavage. A cohort of ethanol-fed mice received SQ 29,548, a TP-R antagonist (ET+SQ, n = 8) by oral administration. Results: Western blot analysis showed that the protein level of thromboxane A2 synthase 1 ( P<0.05), responsible for TXA2 production, was upregulated in the mouse liver upon ethanol exposure. Of note, ethanol feeding significantly increased plasma aspartate transferase (AST) level ( P<0.05), which was abolished by SQ administration ( P<0.05). Moreover, compared with CON mice, ET mice showed an increase in liver protein levels of pro-inflammatory markers, including TNFa ( P<0.05), cluster of differentiation 68 (CD68, P<0.001), and vascular cell adhesion protein 1 ( P<0.05). In addition, the pro-fibrogenic markers including collagen type 1 alpha 1 chain (COL1A1, P<0.05) and matrix metalloproteinase 9 (MMP9, P<0.01) were also increased in ET mice. However, these alterations were not found in ET+SQ mice compared to their controls. In particular, ET+SQ mice exhibited a marked reduction in hepatic protein levels of CD68 ( P<0.001), COL1A1 ( P<0.001), and MMP9 ( P<0.01) versus ET mice. Interestingly, we noted that ethanol consumption decreases the protein level of NADH:ubiquinone oxidoreductase subunit B8 (NDUFB8), a component of mitochondrial complex I, in mouse liver ( P<0.05), which was reversed by SQ administration( P<0.05). Conclusion: These findings suggest that blockade of TP-R activity attenuates ethanol-induced liver inflammation and fibrosis possibly through improving the function of mitochondrial complex I. This study was supported by the NIH-NIAAA P50 award-Alcohol Center of Research-Nebraska (P50AA030407-5130). 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.