bluuebunny/crossref_metadata_2025_split huggingface dataset:
Up‐regulation of Clusterin is Involved in MSC Overexpressing GATA‐4 Mediated Cell Protection
Authors: Yang Yueting , Yu Bin , Liu Huan , Wang Yi‐Gang , Ashraf Muhammad , Xu Meifeng 
Published: June 2021

We have previously reported that GATA‐4 gene transfection in mesenchymal stem cells (MSC) prolongs MSC survival in the ischemic heart and promotes heart repair. Our preliminary studies show that clusterin was prominently upregulated in MSCs overexpressing GATA‐4 (MSCGATA‐4). In this study, we hypothesized that upregulation of clusterin was responsible for GATA‐4 mediated cell protection.Methods and ResultsMSCs were harvested from rat bone marrow and transduced with GATA‐4 by using the murine stem cell virus retroviral expression system. The expression of clusterin in MSCs was documented by real‐time PCR, immunofluorescence, and western blotting. The released clusterin from MSCs was estimated using ELISA. Cardiomyocytes (CM) from neonatal rat ventricles were cultured and exposed to hypoxia and anoxia to mimic ischemic injury. The cytoprotection was determined by measuring lactate dehydrogenase release, MTT intake, Annexin‐V staining, and mitochondrial membrane potential (ΔΨm). Compared to vector‐empty transduced control MSCs, the expression of clusterin was significantly up‐regulated in MSCGATA‐4 accompanied by its significant release from MSCGATA‐4. Direct administration of clusterin protected MSCs and CM against ischemic injury by increased cell survival, reduced apoptosis, and maintenance of ΔΨm. The cytoprotective effect of clusterin was partially abrogated by Akt inhibitor LY294002. Clusterin also significantly augmented expression of p‐Akt in MSCs and CM.ConclusionsIt is concluded that clusterin played a prominent role in MSCGATA‐4 mediated cytoprotection via Akt signaling.
The Form of Energy‐containing Food Alters Satiety and fMRI Brain Responses in Humans
Authors: Soto Marion , Darcel Nicolas , Piedcoq Julien , Tomé Daniel , Fromentin Gilles , Nadkarni Nachiket 
Published: June 2021

We examined the differences in satiety and brain activation after ingestion of apple in the form of juice, puree or slices.25 normal‐weight men had to eat a breakfast consisting of one of three apple products (cross‐over design): apple juice, puree or slices, each with the same caloric content. After breakfast, a fMRI session was conducted as follows: a 'liking' run consisting of viewing images (food and objects) whilst rating their appeal value, and a 'choice' run in which participants had to choose between two images of different categories (high‐fat/low‐fat sweet/savory). Measures of appetite were obtained by using visual analog scales at different times.Consumption of the three apple products led to differences in short‐term satiety, in the order slice > puree > juice. In the 'liking' run, the nucleus accumbens (NAcc), the orbitofrontal cortex (OFC) and the hypothalamus were more activated after consumption of apple juice vs. apple slices. Neural activity in the NAcc and OFC was positively correlated with hunger ratings after breakfast. In the 'choice' run, the OFC was more activated after the juice breakfast vs. slices, when subjects chose sweet images (rather than savory) and high‐fat images (rather than low‐fat). BOLD signal in the OFC measured when high‐fat foods were chosen was positively correlated with hunger ratings and ratings of 'expected pleasure to eat' reported after breakfast.These findings suggest that food form elicits differences in short‐term satiety, and leads to different responses to food cues in limbic (NAcc and OFC) and homeostatic (hypothalamus) regions underlying food intake.
Gastrodin Promotes SGC7901 Apoptosis by Up‐regulating the ProBDNF Signaling Pathway
Authors: jianhui Guo , jinwei Yang , wei Ma , bin Du , jingru Cheng , liyan Li 
Published: June 2021

ObjectiveTo investigate the affect of Gastrodin on human gastric cancer cells (SGC7901) and its relationship with precursor brain‐derived neurotrophic factor proBDNF signal pathway.MethodsSGC‐7901 was cutured in vitro and randomly divided into normal, control and experimental groups, and then, each group was divided into 6, 12, 24, 48 and 72 h groups. The experimental group cells were co‐cultured with Gastrodin at 2 mg/ml, but saline in control groups, and normal groups had no other treatment. After that, 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to detect the cell activity and terminal dexynucleotidyl transferase(TdT)‐mediated dUTP nick end labeling (TUNEL) was used to detect the apoptosis of the cells. Immunofluorescence was used to locate the proBDNF, p75 and Sortilin positive cells, and the expression of proBDNF, p75 and Sortilin mRNA was detected by Real time Polymerase Chain Reaction (PCR).Results1, SGC7901 was successfully cultured. 2, Cell viability in experimental groups was decreased compared with normal or control groups, but the apoptosis was increased. 3, proBDNF, p75 and Sortilin mRNA was up‐regulated in experimental groups.ConclusionGastrodin can decrease the biological activity and increase the apoptosis of SGC7901, and the mechanism may be by increasing the proBDNF apoptosis signal pathway.Corresponding author: Li‐yan Li.
Region‐Specific Expression of ProBDNF and MatureBDNF in Alcohol Preference
Authors: Li Liyan , Ma Wei , Yang Jinwei , Yang Yanlei , Wang Dongyan , Luo Tao , Cheng Jingru , Guo Jianhui 
Published: June 2021

Brain‐derived neurotrophic factor precusor (proBDNF) plays different roles from mature BDNF through different receptors and pathways in the central nerve system (CNS), some research indicated that BDNF plays important roles in alcohol preference in murine, however, the region‐specific BDNF expression remains to be controversial. So we investigated the responsiveness of proBDNF, matureBDNF and their receptors to acute and chronic alcohol exposure in rat. On the one hand, western blot was used for detecting the expression level of proBDNF, TrkB and Sortilin proteins in cortex, hippocampus, amygdala and dorsal striatum after acute alcohol exposure; on the other hand, we successfully established psychomotor sensitization (PS) model for chronic alcohol exposure. RT‐PCR were performed for measuring the mRNA level of BDNF, TrkB, P75NTR and Sortilin in the cortex, hippocampus and dorsal striatum after chronic alcohol exposure. Our research found that mRNAs for BDNF, trkB, p75 and sortilin were detected in all brain regions in both control and alcohol groups. Chronic alcohol exposure upregulated BDNF mRNA level in prefrontal cortex, but decreased Sortilin mRNA level in dorsal striatum. No changes of these mRNAs were found in other brain regions between alcohol group and control group. We conclude that chronic alcohol exposure caused differential expression of BDNF and sortilin in different brain regions, but proBDNF and matureBDNF do not play key roles in alcohol preference.*Corresponding author: Jian‐hui Guo.
Olanzapine Reduces Neuronal Activity in the Dorsal Motor Nucleus of the Vagus
Authors: Anwar Imran , Miyata Kayoko , Zsombok Andrea 
Published: June 2021

Olanzapine, a widely prescribed atypical antipsychotic, relieves the symptoms of schizophrenia and bipolar disorder. Despite its positive impact on mental health, patients treated with olanzapine experience side effects related to weight gain and impaired glucose homeostasis. A variety of mechanisms and brain areas underlying the metabolic side effects have been proposed; however, the involvement of the brainstem remained to be elucidated. Parasympathetic neurons in the dorsal motor nucleus of the vagus (DMV) set the vagal tone and thus control visceral functions including feeding, digestion, and glucose homeostasis. In this study, whole‐cell patch‐clamp recordings were performed to test the hypothesis that olanzapine modulates neuronal activity in the DMV of mice. Acute application of olanzapine (10 µM) hyperpolarized the majority (~70 %) of DMV neurons in male mice by an average of ‐7.77 ± 1.17 mV (n=20). This effect was concentration‐dependent (EC50 = 16.02 ± 1.78 µM), and was associated with a reduction of input resistance. Similarly, hyperpolarization was observed in female mice (n=9). The hyperpolarization also occurred in the presence of tetrodotoxin, suggesting a postsynaptic mechanism of action. Next, stomach‐ and liver‐projecting DMV neurons were identified with transsynaptic retrograde viral labeling. Acute olanzapine application resulted in hyperpolarization of the majority of both liver‐ and stomach‐related DMV neurons. In summary, our data demonstrate that in slices olanzapine administration hyperpolarizes the majority of DMV neurons via postsynaptic mechanisms. These data suggest that olanzapine has the potential to modulate vagal outflow to subdiaphragmatic organs.Supported by: Pilot Project Grant Tulane University School of Medicine
Dietary Nitrate improves Cerebral Perfusion, in Young Adults during Exercise: Relationship to Cognitive Performance
Authors: Rattray Ben , Egle‐Marshall Lauren , Northey Joseph , Hone Simon , Smee Disa , Brassard Patrice 
Published: June 2021

Dietary nitrate increases middle cerebral artery mean velocity (MCA Vmean) during aerobic exercise but it remains unclear if this is true with the simultaneous inclusion of a cognitively demanding task. Therefore, our aim was to investigate whether nitrate supplementation would influence exercise‐induced changes in MCA Vmean, and cognitive performance.In a double blind randomized crossover design, 12 healthy adults consumed two 70 ml doses of either beetroot juice or placebo two hours prior to exercise. Subjects then completed four 8‐min workloads of exercise set to elicit 30%, 50%, 70%, and 85% of heart rate reserve (HRR) on a cycle ergometer. Reaction time and accuracy was assessed during a modified version of the color Stroop task, with simple and complex (incongruent) response types, in the last 3 min of each workload. MCA Vmean (Transcranial Doppler) was monitored throughout.MCA Vmean displayed a typical relationship with exercise intensity, but was significantly elevated with beetroot, especially during the complex Stroop task, at 70% (p=0.001, d=0.47) and 85% HRR (p=0.027, d=0.74). Reaction time was not statistically different between conditions regardless of the difficulty level. However, beetroot may have contributed to increased accuracy in the complex task (p=0.059) whilst cycling.These preliminary results suggest that dietary nitrate elevates MCA Vmean during a combined exercise and cognitive challenge, which may be related to improved accuracy during the most demanding tasks.
ICP During Daily Life in Healthy Adults: What Does Microgravity Add to the Mix?
Authors: Lawley Justin , Williams Michael , Petersen Lonnie , Zhang Rong , Whitworth Tony , Levine Benjamin 
Published: June 2021

PURPOSEDue to visual changes seen in astronauts, the primary objective is to make the first direct, invasive measurements of intracranial pressure (ICP) during changes in hydrostatic gradients experienced during daily life and induced by simulated and real microgravity.METHODSSubjects are four healthy adults who previously had an Ommaya reservoir implanted, which allows continuous pressure measurements to be made. Central venous pressure (CVP) is measured by a peripherally inserted central catheter. Hemodynamics are obtained upright, supine, then after 5 min, 3 hrs and 24 hrs of 6° head‐down tilt (HDT). Measurements are repeated during real microgravity (parabolic flight).RESULTSICP increased by transitioning from the sitting to supine position (4±2 vs 15±2 mmHg); ICP increased further with HDT (17±3, Δ2 mmHg), but returned towards normal values after 3 hrs (16 mmHg) and 24 hrs (14 mmHg). In comparison to the supine position, CVP tended to decrease over time during HDT (5 min, Δ1 mmHg; 3 hrs, Δ2 mmHg; 24 hrs, Δ1 mmHg). ICP increased during the 1.8g (Gx) phase of the parabola (from supine 17±2 to 25±2). However, ICP fell dramatically during 0g (to 13±4, Δ12 mmHg). The magnitude of the reduction in ICP is the combination of removing the 1.8 Gx and the subsequent fall in CVP (1g, 5±4; 1.8g, 7±5; 0g, 4±3).imageConclusionsElevated ICP is unlikely to be the culprit for visual impairment in space. Alternatively, visual impairments may be simply due to consistently “elevated” ICP relative to the upright posture, due to the inability to “stand‐up” in space.
Lumbar Paraspinal Muscle Atrophy during Long Duration Spaceflight
Authors: Snyder Alex , Macias Brandon , Healey Rob , Holt Jacquelyn , Chang Douglas , Lotz Jeffrey , Hargens Alan 
Published: June 2021

Spaceflight results in significant lumbar pain and muscle atrophy in astronauts. The rate of disc herniation is about four times greater in US astronauts than in matched controls. Muscles are vital spine stabilizers, and trunk muscle atrophy is associated with chronic back pain. Yet, it is unclear whether current countermeasures during 6‐month International Space Station (ISS) missions prevent lumbar paraspinal muscle atrophy.PURPOSETo quantify paraspinal muscle functional cross sectional area (FCSA) before, immediately after, and 30‐days after 6‐month ISS missions.METHODSTo date, complete paraspinal MRI data for three astronauts were available. FCSA was measured in four lumbar paraspinal muscles (multifidus, erector spinae, quadratus lumborum, and psoas) at lumbar vertebral level 3/4. FCSA was measured by setting a threshold to isolate lean muscle.RESULTSLong duration spaceflight produced a significant 15.1% decrease (p=0.023) in total lumbar paraspinal muscle FCSA, as compared to before flight (Table 1). Subsequently 63.3% of FCSA loss was recovered by 30‐days post flight and was not significantly different from before flight (p=0.152).imageCONCLUSIONDespite low sample size, paraspinal muscle atrophy is not prevented by current countermeasures on 6‐month ISS missions. However, recovery activities resulted in a 63% recovery 30‐days post flight. This suggests spaceflight induced back pain and disc herniation risk may be partly related to reduced dynamic trunk stability linked to atrophied lumbar paraspinal muscles.Project supported by NASA grant # NNX13AM89G (to ARH) and NSBRI through NASA NCC 9‐58 (to BRM).
AT1R Blockade Attenuates Reflex Cutaneous Vasoconstriction in Aged but not Young Skin
Authors: Lang James , Kolb Kelsey 
Published: June 2021

Stimulation of the angiotensin II type I receptor (AT1R) elicits vasoconstriction (VC) that may be occurring through the activation of a pathogenic vascular pathway such as Rho kinase (ROCK). We hypothesize that the reflex cutaneous VC response to whole‐body cooling (Tsk = 30.5 oC) in older humans relies in part on AT1R activation, which may explain greater ROCK activity attendant with aging. Two microdialysis (MD) fibers were placed in the forearm skin of 10 young (Y) (24 ± 1 years) and 10 older (O) (70 ± 2 years) individuals for infusion of 1) lactated Ringer's solution (control) and 2) AT1R blockade with 2 μg/L losartan. Laser Doppler flux (LDF) was measured over each MD site and cutaneous vascular conductance (CVC) was calculated as CVC = LDF/mean arterial pressure and expressed as a percent change from baseline (%ΔCVC). In older individuals the VC response to whole‐body cooling was blunted (Y = ‐34 ± 2, O = ‐17 ± 3 %ΔCVC) and this was further attenuated at the losartan site (Y = ‐34 ± 3, O = ‐9 ± 3 %ΔCVC; P < 0.05). The VC response to an exogenous 10 μM dose of angiotensin II (Y = ‐27 ± 3, O = ‐42 ± 5 %ΔCVC) was completely blocked in sites pretreated with losartan or with fasudil, a ROCK antagonist. These data suggest that AT1R activation contributes to the reflex VC response in aged but not young skin. Furthermore, the angiotensin II component of the VC response appears to occur primarily through a ROCK‐mediated mechanism.**Funded by Iowa Osteopathic & Education Research Grant (IOER #05‐13‐05)
Deprivation of plasma estradiol level affects circadian rhythms of body core and tail skin temperature in female rats
Authors: Marui Shuri , Nagashima Kei 
Published: June 2021

PurposeWe aimed to assess the effect of estradiol on daily changes of thermoregulatory responses of the tail vasculature in ovariectomized rats.MethodsFemale Wistar rats (n=10, age of 8‐12 wk) were bilaterally ovariectomized, and placed a telemetry device for the measurements of body core temperature (Tcore) and spontaneous activity (ACT) in the abdominal cavity. Temperature of the tail surface (Ttail) was estimated by thermography. Two silicon tubes containing 17β‐estradiol (E2, 50mg) were subcutaneously placed in one group (n=5, E2 (+)), and empty tubes were placed in the other group (n=5, E2 (‐)). The tubes were removed 10 days after the surgery. Tcore, ACT, and Ttail were measured a day before and 14 days after the removal of the tubes (PRE and Day 14, respectively). Regression analysis was conducted for the relationship between the daily values of Tcore and Ttail.ResultsOn the PRE, Tcore was higher (P<0.05) in the E2 (‐) group than in the E2 (+) group at 12:30‐17:00 (37.2±0.2°C and 36.5±0.2°C, respectively). Ttail was higher (P<0.05) in the E2 (‐) group than the E2 (+) group at 20:00‐0:30 (33.4±0.3°C and 31.2±0.6°C, respectively). The regression slope for Ttail and Tcore was greater (P<0.05) in the E2 (‐) group than in the E2 (+) group on the PRE (1.41±0.34 and 0.60±0.16, respectively). On Day 14, in the E2 (‐) group, circadian rhythms of Tcore and Ttail remained unchanged from those on the PRE. Tcore and Ttail were higher than those on PRE at 14:30‐18:30 and 19:00‐18:30, respectively. The regression slope was greater (P<0.05) than that of the PRE.ConclusionA reduction of estradiol affects circadian rhythms of Tcore and Ttail. Moreover, a lack of estradiol may decrease the ability in thermoregulatory response of the tail vasculature.
Lisinopril Improves Cutaneous Microvascular Function in Hypertensive Men and Women
Authors: Craighead Daniel , Kenney W Larry , Alexander Lacy 
Published: June 2021

Hypertension is a chronic disease that induces microvascular dysfunction through upregulation of arginase and inducible nitric oxide synthase (iNOS) resulting in a loss of endothelial (e)NOS‐dependent vasodilation. Angiotensin converting enzyme inhibitors may have off‐target beneficial vascular effects on endothelial signaling and microvessel structure. We hypothesized that treatment with Lisinopril (>3 month) would improve cutaneous microvascular function in hypertensive adults. Four intradermal microdialysis fibers were placed in the forearm skin of 6 controlled hypertensive subjects (Lisinopril (LIS): MAP 94 mmHg), 9 hypertensive (HTN: MAP 111 mmHg) and 10 age matched normotensive (NTN: MAP 86 mmHg) subjects. Ringer's solution (control), 20mM L‐NAME (NOS inhibited), 0.1mM 1400w (iNOS inhibited), and 5mM BEC (arginase inhibited) were perfused through the fibers. Red cell flux was measured by laser‐Doppler flowmetry (LDF) during an acetylcholine (ACh) dose‐response (0.01mM‐100mM ACh). Cutaneous vascular conductance (CVC=LDF/MAP) was calculated and normalized to a percent of maximum (%CVCmax: 28mM SNP). SNP‐induced maximum vasodilation (CVCmax) was also assessed. There were no differences in ACh‐induced vasodilation between the LIS and NTN groups. LIS treatment improved %CVCmax responses to ACh compared to unmedicated HTN (all ACh doses 蠅 1mM p<0.05). Neither iNOS nor arginase inhibition altered the %CVCmax response to ACh in the LIS group (vs. control site). CVCmax was attenuated in HTN (1.57 ± 0.6 vs NTN 1.75 ± 0.6, p<0.05) and not improved in LIS (1.64 ± 0.5, p=0.33). These data suggest that pharmacotherapy for essential hypertension with Lisinopril improves eNOS‐dependent but not SNP‐induced maximal vasodilation in hypertensive adults.NIH R01 HL089302
Exercise‐Induced Heat Stress Disrupts the Shear‐Dilatory Relationship in the Brachial Artery
Authors: Ives Stephen , Lefferts Wesley , Wharton Margret , Fehling Patricia , Smith Denise 
Published: June 2021

Heat stress increases cardiovascular strain and is of particular concern in occupations, such as military personnel and firefighters, where individuals are required to perform strenuous work while wearing personal protective equipment (PPE). Sudden cardiac events are the leading cause of duty‐related death among firefighters, accounting for ~50% of fatalities each year. Increased cardiovascular strain may initiate an ischemic condition and heat stress may exacerbate this condition. Understanding the acute effects of exercise‐induced heat stress (EIHS) on vascular reactivity may provide insight into mechanisms precipitating acute coronary events in firefighters.METHODSUsing a balanced crossover design, 12 young healthy males performed 100 minutes of moderate‐intensity, intermittent exercise with and without EIHS (PPE or cooling vest, respectively). Measurements of FMD and reactive hyperemia (RH) were performed pre‐ and post‐exercise. RESULTS: During EIHS core temperature was significantly greater (38±0.1 vs. 37±0.1°C). Post‐exercise FMD tended to be suppressed in both conditions, but there were no statistical differences. RH was reduced following control but was increased following EIHS. Thus, normalizing FMD to the shear stimulus (FMD/SSAUC) revealed a significant reduction in FMD following EIHS only (Pre: 0.22±0.1 and 0.13 ±0.0 vs. post: 0.26±0.1 and 0.05±0.0 %FMD/SSAUC, control vs. EIHS, respectively). CONCLUSIONAcute intermittent moderate‐intensity exercise tends to reduce large artery endothelial function, which was aggravated by heat stress, and this may contribute to increased risk of acute coronary events. Support: DHS# EMW‐2010‐FP‐01992.
Effect of Beetroot Juice Supplementation on Conduit Artery and Microvascular Hemodynamics During Small Muscle Mass Handgrip Exercise
Authors: Craig Jesse , Broxterman Ryan , Barstow Thomas 
Published: June 2021

Beetroot juice (BR) supplementation has been shown to have positive ergogenic effects on blood flow (Q) as well as mitochondrial and muscle efficiency during large muscle mass aerobic exercise in animals and man.PurposeTo determine if the previously demonstrated effects of BR translate to small muscle mass exercise.MethodsSubjects completed constant power two‐handed handgrip tests at 40% peak power for 10 min under both BR and placebo (PLA) conditions. Mean arterial pressure (MAP) was measured using an automated cuff, Q was measured in the brachial artery via Doppler ultrasound, and muscle oxygenation characteristics were measured in the flexor digitorum superficialis (FDS) using near infrared spectroscopy.ResultsBR decreased resting MAP (76.3 ± 3.4 vs 84.1 ± 5.7 mmHg, p=0.014) but did not significantly lower exercising values. There were no significant differences in Q or vascular conductance between conditions. There were no significant differences between FDS deoxy‐[Hb+Mb] at rest or during the first minute of exercise, but after an initial overshoot PLA deoxy‐[Hb+Mb] decreased to a lower steady‐state value, while BR remained significantly elevated (49.3 ± 0.96 vs 43.8 ± 0.31 μM, p<0.013) until min 8. BR deoxy‐[Hb+Mb] decreased to values similar to PLA for min 8 through 10. FDS total‐[Hb+Mb] was not significantly different at rest or during exercise.ConclusionThese preliminary findings suggest that BR may have no effect on Q during moderate intensity small muscle mass exercise. Contrary to contemporary findings in large muscle mass exercise, BR may lead to an increased deoxy‐[Hb+Mb] in small muscle mass exercise.