bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute nitrate supplementation lowers retrograde shear stress in post‐menopausal women
Authors: Somani Yasina , Kim Jin‐Kwang , Burke Olivia , Moore David , Grine Kristen , Jiang Dongsheng , Flanagan Michael , Proctor David 
Published: November 2023

PurposeShear patterns in large conduit arteries are an important determinant of vascular health. More specifically, high levels of retrograde and oscillatory shear stress are associated with reduced endothelium‐mediated dilation. In the present study, we employed a double‐blind randomized cross‐over design to examine the effects of an acute dose of dietary nitrate supplementation on resting brachial artery shear patterns in post‐menopausal women.MethodsTen post‐menopausal women (age: 60–64 years; resting blood pressure: 125 ± 12/78 ± 10 mmHg) consumed beetroot juice (BrJnitrate; 140 mL) or a placebo (BrJplacebo; 140 mL of nitrate‐depleted beetroot juice, James White Beet‐It Sport; IND#119978) on two visits separated by one week. 120 minutes following juice consumption, brachial artery diameter and velocities were measured using Doppler ultrasound. Brachial artery diameter was assessed using edge detection software and oscillatory shear was calculated based on retrograde and antegrade shear rate.ResultsA lower retrograde shear rate was observed following BrJnitrate vs. BrJplacebo consumption (−4.2 ± 1.6 vs. −7.9 ± 1.9 s−1, p < 0.05). Although statistical significance was not reached, lower oscillatory shear was exhibited following BrJnitrate vs. BrJplacebo consumption (0.10 ± 0.03 vs. 0.21 ± 0.06 a.u., p = 0.055).ConclusionOur findings suggest that acute nitrate supplementation improves conduit shear patterns in older women, a population at heightened risk of cardiovascular disease. The lower retrograde shear stress, as well as the downward trend observed in oscillatory shear, suggests that nitrate supplementation may be vasoprotective in post‐menopausal women.Support or Funding InformationPenn State Ambulatory Research Fund (Jaffe Endowment)
Impact of air temperature on core temperature regulation during exercise using a simulated burn injury model
Authors: Cramer Matthew N. , Moralez Gilbert , Kouda Ken , Gagnon Daniel , Crandall Craig G. 
Published: November 2023

Following a burn injury, excision of injured skin and subsequent grafting lead to attenuated sweating rates and thereby a diminished capacity for evaporative heat loss, resulting in exacerbated elevations in core temperature and greater risk of heat illness during physical activities. Since the capacity for evaporation is dependent on the absolute area of non‐injured body surface area (BSA), and the heat load imposed on the body reflects both metabolic and environmental sources of heat gain, the detrimental effect of a burn injury on core temperature regulation during exercise at a given intensity is likely dependent on the interaction between the size of a burn injury and the prevailing air temperature. To test this possibility, four healthy males (23 ± 3 years, 80.1 ± 11.1 kg, 1.98 ± 0.15 m2) visited the laboratory on eight occasions to complete 1 h of cycling at a fixed rate of metabolic heat production (~6 W/kg; indirect calorimetry) in a 39°C or 24°C environment (20% relative humidity) with a simulated burn injury of 0%, 20%, 40%, or 60% BSA. Burn injuries were simulated by covering skin on the torso, arms, and legs with highly absorbent, vapor‐impermeable material that impedes sweat evaporation. Core temperature was measured in the gastrointestinal tract (Tgi). Elevations in Tgi at 24°C were not different across all simulated burn injury levels (0%: 0.81 ± 0.13°C, 20%: 0.70 ± 0.20°C, 40%: 0.78 ± 0.14°C, 60%: 0.65 ± 0.16°C; P ≥ 0.32). At 39°C, the increase in Tgi was not different between 0% (0.83 ± 0.24°C), 20% (0.96 ± 0.35°C), and 40% (0.99 ± 0.15°C) simulated burn injuries (P ≥ 0.60), but the rise in Tgi with a 60% simulated burn injury (1.84 ± 0.16°C) was greater than the other “injury” levels (P<0.05). Consistent with this observation, elevations in Tgi were exacerbated at 39°C versus 24°C only with a 60% simulated burn injury (P<0.01). In summary, core temperature reached similarly elevated levels following 1 h of moderate‐intensity exercise with simulated burn injuries of 20%, 40%, and 60% of BSA under temperate environmental conditions, and with simulated burn injuries of 20% and 40% in hot conditions. However, exercise in the heat at the same intensity with a 60% BSA simulated burn injury resulted in a greatly exacerbated elevation in Tgi. Therefore, burn survivors with injuries spanning 60% of total BSA may be exposed to a greater risk of hyperthermia and heat illness when working at a fixed intensity in a hot environment.Support or Funding InformationFunding: Department of Defense – US Army, W81XWH‐15‐1‐0647
Weight Loss‐Induced Changes in Muscle Protein Turnover in Young Men: Effects of Dietary Protein Intake and Resistance Exercise
Authors: Hector Amy , McGlory Chris , Damas Felipe , Phillips Stuart 
Published: November 2023

A negative consequence of diet‐induced weight loss is the loss of lean body mass (LBM), particularly muscle mass, which is induced by an imbalance between rates of muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Increased protein intake and resistance exercise during diet‐induced weight loss promote retention of LBM [1] by stimulating MPS. Currently, the relative contribution of MPS to hypoenergetic diet‐induced LBM loss, and the effect of protein intake and resistance exercise on these variables is not well characterized. In a single blind investigation, adult men (n=24, BMI=28.6±0.6kg/m2, age=22±1y) underwent 10 days of a controlled diet with a 40% reduction in energy intake to create an energy deficit, while performing unilateral resistance exercise and consuming either lower protein (LP) (1.2g/kg/d protein, n=12) or higher protein (HP) (2.4g/kg/d protein, n=12). Pre‐ and post‐intervention testing included DXA, primed constant infusion of ring‐[13C6]‐phenylalanine to measure acute MPS in the fasted state and skeletal muscle biopsies to measure gene and protein expression. Total weight loss (−1.7±0.1kg) and fat mass loss (−0.7±0.1kg) did not differ between groups; however, appendicular lean mass of the exercised leg was preserved compared to the rested leg in both groups (exercise= −0.1±0.1kg, rest= −0.4±0.1kg, p<0.05). Mixed MPS was significantly reduced in both groups following weight loss (HP= −14±4% and LP= −27±2%, p<0.05). In the exercised leg, mixed MPS was preserved in the lower protein group and elevated above baseline in the higher protein group (14±6% p<0.05) 48 hrs following the last exercise bout. Gene expression of TRAF6 was increased in the rested leg of the lower protein group (p<0.05), but there was no change in TRAF6 protein expression at any time point in either group. Gene expression of other targets in the ubiquitin‐proteasome and autophagic‐lysosomal pathways (Atrogin‐1, MuRF‐1, Foxo3a, LC3, Gabarapl1, Ulk2, Beclin1) did not change with weight loss in either group. Protein expression of p‐Foxo3a (Ser253) and p‐TSC2 (Thr1462) also did not change with weight loss in either group. These results suggest that reductions in MPS are the likely reason for LBM loss during the early phase of diet‐induced weight loss. Resistance exercise can help to preserve (LP) or even elevate (HP) rates of fasted MPS, which, in concordance with our earlier work [1], promotes LBM retention.Support or Funding InformationSupported by NSERC and OGS
Acute Effects of Incremental Resistance Training on Muscle Function in Older Adults
Authors: Abdul Majid Mufaqam Syed , Mills‐Gray Susan L , Parks Elizabeth Jane , Ball Stephen Daniel 
Published: November 2023

The population of older adults is growing significantly and is expected to reach 56.4 million by the year 2020. Aging reduces muscle mass that leads to decreases in muscle strength, flexibility, and balance in older adults and sedentary lifestyle increases the rate of progression of these conditions. Increased muscle mass and strength are associated with improved flexibility and balance, and resistance training (RT) may improve all of these aspects of aging.PURPOSEThe purpose of this study was to determine whether an 8‐week program of incremental RT (iRT) improves muscle strength and function in older adults.METHODSEighteen participants (men: n=2, women: n=16, age=61±4 y) performed iRT twice weekly for an hour for eight weeks. Dual‐x‐ray absorptiometry (DXA) scans, surface electromyography (S‐EMG, measured during bicep curl with progressive increases in weights, 0, 3, and 5 lbs.), a strength test (hand dynamometer), and plasma biochemical assays were performed at the beginning and end of the program.RESULTSiRT was associated with a reduction in BMI (32±6 vs. 31±5, P<0.001), body weight (90.0±18.1 kg vs. 87.5±17.4 kg, P<0.001) and %total body fat (40.3±5.7% vs. 39.2±5.2%, p<0.05). Lean mass increased (57.1±5.6% vs. 58.2±5.2%, P<0.05). Muscle strength tended to increase (63.5±13.5 kg vs. 64.7±12.2 kg, P<0.09), as did the efficiency of bicep EMG activity (P=0.07). Although the reduction in plasma creatinine kinase isozyme for muscle (CK‐MM) was not significant (107.6±66.1 U/L vs. 101.7±77.5 U/L, P=0.37), plasma aldolase was significantly reduced 35% (6.6±1.6 U/L vs. 4.2±1.9 U/L, P<0.001).CONCLUSIONPost 8‐weeks of iRT, body weight was reduced by 3% even though weight loss was not a primary goal of the program. Furthermore, the loss in weight was attributed to a decrease in fat mass. Importantly, a significant decrease in plasma aldolase supported the effect of iRT to preserve muscle mass in older adults. Gains in muscle strength and EMG activity indicate enhanced muscle function which should improve overall quality of life during aging.Support or Funding InformationUniversity if Missouri Extension
Prostate Cancer Reduces Endurance Exercise Capacity in the Rat: Possible Roles of Reduced Cardiac Mass and Function
Authors: Rollins Korynne S , Esau Peter J , Gittemeier Elizabeth M , Opoku‐Acheampong Alexander B , Behnke Bradley J , Copp Steven W 
Published: November 2023

Prostate cancer is the most commonly diagnosed non‐skin cancer in men. Exercise intolerance is common in prostate cancer patients; particularly those subject to androgen deprivation therapy. Whether prostate cancer itself reduces exercise capacity is unknown.ObjectiveWe used a preclinical rat prostate tumor model to test the hypothesis that untreated prostate cancer reduces endurance exercise capacity.MethodsSixteen male Copenhagen rats performed an initial treadmill test to exhaustion. The rats' prostates were subsequently injected with either prostate carcinoma cells (R‐3327 AT‐1 cell line) in Matrigel (cancer, n=9) or Matrigel only (sham, n=7) and the treadmill tests were repeated eight weeks post‐surgery. Following the final treadmill test, left ventricle contractility (left ventricle Δpressure/Δtime) was measured under anesthesia and the heart and gastrocnemius muscles were then dissected and weighed.ResultsAverage prostate tumor mass in the cancer group was 9.8±2.6 g (range: 0.2 to 19.5 g). Initial times to exhaustion were not significantly different between groups (sham: 29.8±1.3, cancer: 28.6±2.5 min, p=0.710). Time to exhaustion at eight weeks post‐surgery was reduced compared to initial values for both groups but the eight‐week time to exhaustion was significantly lower in the cancer group (13.3±1.4 min) compared to the sham group (19.7±2.1 min, p=0.019). Left ventricle Δpressure/Δtime was not significantly different between groups, but within the cancer group prostate tumor mass was significantly inversely correlated to left ventricle Δpressure/Δtime (−0.71, p=0.047). Total body mass was not significantly different between groups (p=0.363) but heart (↓12%, p=0.021), left ventricle (↓16%, p=0.003) and gastrocnemius (↓9%, p=0.005) muscle mass were significantly lower in the cancer group compared to the sham group. Within the cancer group heart (r=−0.74, p=0.22) and left ventricle (r=−0.85, p=0.004) mass, but not gastrocnemius muscle mass (r=−0.15, p=0.696), were inversely correlated with prostate tumor mass. In other words, within the cancer group the rats with the largest prostate tumors had the lowest cardiac contractility, the smallest heart mass, and, more specifically, the smallest left ventricle mass.ConclusionWe found that untreated prostate cancer reduced endurance exercise capacity in rats. Although multiple mechanisms likely contributed to the reduced exercise capacity in rats with prostate cancer, reductions in cardiac muscle function and mass, as well as reductions in gastrocnemius muscle mass, likely played an important role.Support or Funding InformationAmerican Cancer Society (RSG‐14‐150‐01‐CCE to BJB)
Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism
Authors: von Walden Ferdinand , Gidlund Eva‐Karin , Venojärvi Mika , Heinonen Olli , Norrbom Jessica , Sundberg Carl‐Johan 
Published: November 2023

Humanin (HN) is a mitochondrially encoded and secreted peptide linked to glucose metabolism and tissue protecting mechanisms. Plasma HN levels are lower in people with type 2 diabetes. Whether skeletal muscle HN expression is influenced by exercise is unknown. Therefore, the aim of this study was to investigate serum and skeletal muscle HN levels in men with impaired glucose control in response to 12 weeks of either resistance or aerobic (nordic walking) training.Men (n=55) with impaired glucose regulation (IGR) were recruited and randomly assigned to resistance training (RT), Nordic walking (NW) or control (CON). Subjects trained three times per week for twelve weeks with progressively increased intensity during the intervention period. Biopsies from the vastus lateralis muscle and venous blood samples were taken before and after the intervention. A 2‐hr oral glucose tolerance test (OGTT) with 75 g of glucose loading was performed before and after the intervention period. Skeletal muscle and serum HN protein levels and skeletal muscle gene expression of MT‐NRN2 (the 16S gene), MT‐NRN1 (the 12S gene) and HNM1 were analyzed.Skeletal muscle HN protein levels increased by 35 % after twelve weeks of resistance training (time × group interaction p=0.022). No significant interactions over time were seen in the NW or the C groups (ns). In the RT group, ΔHN serum protein concentration was correlated to the improvement of 2‐hr glucose loading test (R= 0.597, p=0.019). Twelve weeks of either RT or NW did not change mRNA levels of MT‐NRN2, MT‐NRN1 or of HNM1. There was a significant increase in citrate synthase activity in the RT group (1.8‐fold ± 0.47 p<0.05, time × group interaction p=0.027).HN protein levels in skeletal muscle increase after regular resistance training in pre‐diabetic men. The significant correlation between ΔHN serum levels and improvements in the 2‐hr time point of the OGTT suggests a role for HN in the regulation of glucose metabolism. Given the preventative effect of exercise on diabetes type 2, the role of HN as a mitochondrially derived peptide and an exercise‐responsive mitokine warrants further investigation.Support or Funding InformationThe study was supported by grants from the Research Council for Physical Education and Sports, of the Finnish Ministry of Education, of Turku University of Applied Sciences R&D program and from Karolinska Institutet, Department of Physiology & Pharmacology.
Oral administration of BGP‐15 significantly increases HSP72 expression and attenuates ventilator‐induced diaphragm dysfunction
Authors: Morton Aaron B , Smuder Ashley J , Hall Stephanie E , Wiggs Michael P , Powers Scott K 
Published: November 2023

Mechanical ventilation (MV) is a life‐saving intervention for patients unable to sustain adequate pulmonary gas exchange on their own. Unfortunately, prolonged MV results in rapid atrophy and contractile dysfunction of the diaphragm, collectively termed ventilator‐induced diaphragm dysfunction (VIDD). Although the mechanisms responsible for VIDD remain elusive, it is established that increased mitochondrial production of reactive oxygen species (ROS) is required for the development of VIDD. Notably, recent evidence reveals that endurance exercise training performed prior to MV is sufficient to protect the diaphragm against VIDD. While the mechanisms responsible for exercise‐induced prevention of VIDD remain unknown, evidence suggests that endurance exercise training may reduce diaphragm oxidative damage by elevating heat shock protein 72 (HSP72) expression. Therefore, these experiments tested the hypothesis that oral administration of a pharmacological inducer of HSP72 expression (BGP‐15) would increase HSP72 expression and attenuate VIDD. Our data reveal that 5 days of oral administration of BGP‐15 prior to prolonged MV results in increased HSP72 expression in the diaphragm and protection against VIDD. Specifically, BGP‐15 administration resulted in the prevention of the MV‐induced decrease in diaphragm muscle cross sectional area. Further, treatment with BGP‐15 protected against both MV‐induced diaphragm contractile dysfunction and attenuated the increase in mitochondrial ROS production in the diaphragm. Collectively, these results reveal that oral administration of BGP‐15 provides protection against VIDD presumably through an increase in HSP72.Support or Funding InformationSupported by NIH R01 AR064189 awarded to SKP
Overexpression of SIRT6 Suppresses TNFα‐induced Muscle Cell Atrophy via NFκB Inhibition
Authors: Yeo Dongwook , Kang Chounghun , Ji LiLi 
Published: November 2023

Chronic inflammation is a primary cause of muscle atrophy partly due to nuclear factor (NF)κB‐mediated upregulation of pro‐inflammatory cytokines such as TNFα, IL‐6, and IL‐1β. SIRT6, a NAD+ dependent histone deacetylase has been shown to suppress inflammatory responses by inhibiting NFκB signaling in several mammalian cells, but its role in muscle atrophy has never been studied.PURPOSEThe aim of this study was to investigate whether SIRT6 overexpression (OE) can prevent TNFα‐induced proteolysis and atrophy in skeletal muscle cells.METHODSC2C12 cells were cultured in DMEM supplemented with 10% FBS, 100 U/ml pen:strep in 37°C with 5% CO2 incubator. Transient transfections were performed with 2 ng of GFP or Flag‐SIRT6 DNA transfected with PEI transfection reagent in 70% confluency cells. After 24 h, various doses of TNFα were added and the cells were incubated for various times.RESULTSAfter 48 h TNFα‐treated cells decreased SIRT6 level in a dose‐dependent manner, whereas this effect was abolished in SIRT6 OE cells. GFP+TNFα decreased IκBα content and increased nuclear p65 level indicating NFκB activation; however, SIRT6+TNFα cells showed minimal effect compared to GFP+TNFα. P65 DNA binding was increased by 6.7, 3.5, 4.2, 3.9‐fold with GFP+TNFα at 10min, 1h, 2h, and 6h, respectively (P<0.01); however, SIRT6 OE cells showed 12, 20, and 31% less activation than GFP+TNFα at the above‐mentioned corresponding time points (P<0.05) IL‐6 levels in GFP increased with TNFα at 1h (P<0.05) but were reduced by 18, 13, and 14% (P<0.05) with SIRT6 OE at 1h, 3h, and 6h, respectively. IL‐1β level in GFP was increased by 28% with TNFα 3h (P<0.05), whereas this effect was abolished in SIRT6 OE cells. TNFα treatment increased reactive oxygen species (ROS) production in a dose‐dependent manner (P<0.05), but ROS showed no change with SIRT6 OE. E3 ubiquitin ligase Atrogin‐1 level increased in response to TNFα in GFP but not in SIRT6 OE cells. TNFα treatment increased MuRF‐1 levels in GFP+TNFα; however, the effect tends to be lower in SIRT6 OE cells. The cell viability was decreased in TNFα treatment (P<0.01), but not in SIRT6 OE cells.CONCLUSIONOverexpression of SIRT6 reduced pro‐inflammatory cytokine transactivation and ROS production, and improved viabilities possibly due to inhibition of TNFα‐induced NFκB activation in C2C12 cells.
Manual Acupuncture, but not Electroacupuncture Stimulate Afferent Nerves through Activation of TRPV1 Receptors to Modulate Pressor Reflexes
Authors: Guo Zhiling , Fu Liang‐Wu , Su Hou‐Fen , Longhurst John C. 
Published: November 2023

We have shown that manual acupuncture (MA) at the P6 acupoint and electroacupuncture at the P5‐6 acupoints stimulate afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, mechanisms underlying MA and EA activation of these sensory afferents and their cell bodies in the dorsal root ganglia (DRG) are unknown. A histological study demonstrated that, compared to non‐acupoints, TRPV1 receptors are expressed in greater quantities in sensory nerve fibers located in the area of the ST36 acupoint. It remains unclear if TRPV1 receptors at the P5‐6 areas and DRG neurons contribute to activation of sensory nerves by MA and EA, leading to modulation of pressor responses. Therefore, in the present study, we investigated sensory neural mechanisms by which acupuncture inhibited cardiovascular responses. We hypothesized that acupuncture stimulates afferent nerves through activation of TRPV1 receptors to modulate pressor reflexes. In rats, we found that phasic single‐unit MN activity evoked by MA at P6 was significantly attenuated (P<0.05) by local administration of Iodoresiniferatoxin (a selective TRPV1 receptor antagonist, n=12), but not 5% Dimethyl sulfoxide (DMSO; vehicle, n=12) into the acupoint. Administration of Iodoresiniferatoxin into P5‐6 did not reduce EA‐evoked single‐unit MN activity (n=8). We also observed that MA at P6 and EA at P5‐6 induced phosphorylation of extracellular signal‐regulated kinases (ERK; an intracellular signaling messenger involved in cellular excitation) in DRG neurons at spinal levels of C6‐T1 that receive MN inputs. After knocking‐down of DRG TRPV1 receptors at these spinal levels with intrathecal injection of siRNA, expression of phosphorylated ERK in DRG neurons was reduced by MA, but not EA. Moreover, local injection of Iodoresiniferatoxin (n=5), but not 5% DMSO (n=5) into P6 reversed the inhibitory action of MA at this acupoint on pressor reflexes induced by gastric distension. However, the inhibitory effect of EA at P5‐6 on pressor responses evoked by gastric distension was not reversed after administration of Iodoresiniferatoxin into P5‐6 in two separate rats. Thus, these data suggest that MA, but not EA activate sensory afferents through stimulation of TRPV1 receptors to inhibit reflex increases in blood pressure.Support or Funding InformationNIH grant AT009347