bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locally‐Mediated Cutaneous Vasoconstriction is Augmented in Essential Hypertensive Humans
Authors: Smith Caroline J , Holowatz Lacy A 
Published: June 2021

Essential hypertension (HT) is associated with augmented vasoconstriction (VC) which may be secondary to increased Rho/Rho‐Kinase (ROCK)‐dependent mechanisms. Our aim was to assess the magnitude of cutaneous VC to local cooling as a stimulus to induce ROCK‐mediated VC. Four microdialysis fibers were placed in the forearm of 5 hypertensive (MAP: 103 ± 4 mmHg) and 7 normotensive (NT; 89 ± 7 mmHg) men and women: Ringers (control; C), 3 mM fasudil (ROCK inhibited), 5 mM yohimbine + 1 mM proprananol (α‐ and β‐adrenoceptor inhibited; Y + P), Y + P + 3 mM fasudil (ROCK and adrenocepor inhibited; Y + P + F). Skin blood flow was measured and cutaneous vascular conductance was calculated (ΔCVC) during early and late stage local cooling (24°C) to induce VC via adrenergic and ROCK‐dependent mechanisms, respectively. Greater basal VC (Tsk 34°C) was observed in HT compared to NT (0.00 ± 0.05 vs. 0.28 ± 0.06 CVC, P < 0.05). HT show significantly greater VC at both early (1–5 min; −0.10 ± 0.06 vs. 0.21 ± 0.07 ΔCVCbaseline, p < 0.01) and late (36–40 min; −0.32 ± 0.11 vs. −0.07 ± 0.04 ΔCVCbaseline, p < 0.05) stage cooling compared to NT, with a trend towards augmented ROCK‐mediated VC (1–5 min; −0.97 ± 0.26 vs. −0.25 ± 0.22 ΔCVCbaseline, p = 0.07). These data suggest that VC to local cooling was augmented in HT, which may be linked to increased Rho/ROCK mechanisms.Supported by NIH RO1‐HL093238‐02
Exercise capacity is influenced by thermal balance at onset of active/inactive phases of circadian cycle
Authors: Machado Frederico Sander Mansur , Coimbra Candido Celso 
Published: June 2021

The aim of this study was to verify if circadian phase at which exercise is performed influences performance and thermoregulatory adjustments.Wistar rats (n=8), in a L/D cycle of 14/10h with free access to water and food, were used. To establish active and inactive phase of each animal, spontaneous locomotor activity and core temperature (Tc) were continuously recorded during 48h with an implanted telemetric sensor. After acclimatized to running animals were submitted to incremental exercise until fatigue during both the onset of active and inactive phases of circadian Tc rhythm. Time to fatigue (TF), Tc and skin tail temperature (Ttail) were monitored during exercise. Workload (W) and TF were used as performance index.Results confirmed that onset of active phase was followed by peak Tc (p<0.05) while trough was observed just after inactive phase onset (p<0.05). This was accompanied by superior TF and W during inactive compared to active phase (p<0.05). Exercise capacity differences were followed by higher Tc and Ttail before exercise at active phase (p<0.05). After fatigue Ttail remained higher at active phase (p<0.05).We have demonstrated that exercise capacity was indirectly influenced by time of the day through a circadian‐related modulation of heat production and dissipation before and during exercising until fatigue.Financial support: CAPES, CNPq and FAPEMIG.
Activation of the novel estrogen receptor GPR30 reduces blood pressure and renal injury in the streptozotocin (STZ)‐induced diabetic rat infused with angiotensin II
Authors: Maric-Bilkan Christine , Flynn Elizabeth 
Published: June 2021

Our previous studies have shown that supplementation with 17‐β estradiol is renoprotective in the STZ‐induced diabetic rat. The aim of this study was to examine if activation of the novel, membrane‐bound estrogen receptor, GPR30, could mediate some of the renoprotective effects of estrogens.Angiotensin II (200 ng/kg/min) was infused via osmotic minipumps from the onset of diabetes (STZ, 50 mg/kg) for 6 weeks. These female diabetic Sprague‐Dawley rats were then either left untreated (D) or were treated with G1 (400 μg/kg/day via minipump), a GPR30 agonist (D+G1) for additional 3 weeks. Urine protein excretion (UPE) was measured before and after G1 treatment, while mean arterial pressure (MAP), blood glucose, glomerulosclerosis (GSI) and glomerular filtration rate (GFR) were assessed only at the end of the study.While no difference in UPE were observed in the D+G1 between baseline and time of sacrifice, UPE was reduced by 40% compared with the untreated D at the time of sacrifice. G1 also reduced MAP by 22% and attenuated glomerulosclerosis without affecting GFR or blood glucose levels.The study suggests that activating the GPR30 receptor is renoprotective in the STZ‐induced diabetic rat infused with Ang II, possibly via lowering MAP. Supported by RO1DK075832

D (n=4)
D+G1 (n=5)
P value

Baseline
Sacrifice
Baseline
Sacrifice

UPE (mg/day)
81.4±14.1
133±27.8*
66.2±5.78
77.9±13.7#
*0.05 vs Baseline in the same treatment group  #0.05 vs. D at sacrifice

MAP (mmHg)
‐
128±8.99
‐
100±6.30#

Blood glucose (mg/dL)
‐
348±10.9
‐
341±20.7

GFR (ml/min/kidney)
‐
1.62±0.07
‐
1.50±0.09

GSI (AU)
‐
1.60±0.05
‐
1.28±0.08#
The Fast Skeletal Troponin Activator, CK‐2017357, Improves Resistance to Fatigue in Healthy, Conscious Rats
Authors: Kennedy Adam Richard , Heald Nathan , Pakdel Arash , Ryans Julie , Musch Tim , Poole David , Hageman Sue , Copp Steve , Malik Fady , Jasper Jeffrey 
Published: June 2021

Fast skeletal muscle troponin activators, such as CK‐2017357, amplify the sub‐maximal force frequency response in ex vivo and in situ muscle studies, and decrease muscle fatigue in a rat femoral artery ligation model of vascular insufficiency. We report the effects of CK‐2017357 on running fatigue resistance in conscious, healthy rats.

Treadmill running time (aerobic ). Rats were tested at 30m/min until failure; time and distance run were recorded. Oral CK‐ 2017357 at doses of 10 and 20mg/kg, significantly increased running time on the treadmill by 20% over baseline (p<0.01) and 50% over vehicle control (p<0.01).
Rotarod running time (anaerobic). An accelerating rotarod was ramped between 12–25 revolutions per minute (RPM) over 10 minutes after which animals were allowed to continue at 25RPM for a further 5 minutes. CK‐2017357 increased rotarod running time by up to 2‐fold at doses of 1 and 3mg/kg (p<0.05 and p<0.01 respectively vs. vehicle control). Similar effects were seen with other fast skeletal muscle troponin activators but not with caffeine, creatine or phosphoserine.
Fast skeletal troponin activators, such as CK‐2017357, seem to reduce susceptibility to fatigue in healthy rats both in a long distance, endurance assay (treadmill), and in a shorter distance, high‐intensity assay (rotarod). Thus, the mechanism of action may be useful in treating disorders that increase susceptibility to muscle fatigue.
Mechanisms of myocardial alterations induced by chronic high‐salt intake
Authors: Katayama Isis Akemi , Dopona Ellen Priscila Brito , Heimann Joel Claudio 
Published: June 2021

ObjectiveTo evaluate the mechanisms of left (LV) and right (RV) ventricular hypertrophy induced by high salt intake.Methods18‐week‐old male Wistar rats were fed normal (NS: 1.3% NaCl) or high (HS 8%) salt diet since weaning. From the 7th week of age, two HS subgroups received hydralazine or losartan (HZ 15 or LO 20mg/kg/day). Tail blood pressure (BP), cardiac mass to tibial length ratio (CM/TL), cardiomyocyte transverse diameter (TD) and interstitial fibrosis (IF) were measured.Results(mean±SEM – p<0.05, n=8/group): At 18th week of age, BP (mmHg) was higher in HS (142±6) than in NS (112±2). BP in HS+HZ (116±6) and HS+LO (118±2) did not differ from NS. TD (μm) in the LV was higher in HS (19±0.6) and HS+HZ (17±0.8) than in NS (13±0.4) and HS+LO (13±0.8). TD in the RV was higher in HS (16±0.3) and HS+HZ (14±0.4) than in NS (12±0.2) and HS+LO (12±0.8). IF (%) was higher in HS than NS, HS+HZ and HS+LO in both ventricles (LV: HS 0.56±0.08, NS 0.22±0.04, HS+HZ 0.10±0.04 and HS+LO 0.16±0.03) (RV: HS 0.92±0.06, NS 0.32±0.02, HS+HZ 0.52±0.08 and HS+LO 0.56±0.08). CM/TL did not differ among all experimental groups.ConclusionsIn Wistar rats, salt induced cardiac hypertrophy is blood pressure independent and unrelated to changes in ventricular mass. It can be speculated that this result is an angiotensin II type 1 receptor‐dependent mechanism.Supported by FAPESP and CNPq.
Monitoring exercise intensity during long‐term endurance exercise training in aging rats
Authors: Hoffman Marie , Akins Tiffany , Barton Gregory , McKiernan Susan , Aiken Judd , Diffee Gary 
Published: June 2021

Chronic exercise is known to counter a number of deleterious effects of aging. There are a number of difficulties associated with long term exercise training in aged animals, such as matching appropriate training intensities to the declining exercise capacity as animals age. But there is little quantitative information available regarding exercise capacity in very old rats. We conducted a 1 year endurance exercise study in male FBN rats, starting with rats at age 24 mo and continuing daily until 36 mo of age. Rats were divided into 3 groups; high intensity (H), and moderate intensity treadmill exercise (M), and sedentary (S). M and H animals trained at 13 m/min for 30 min/day, with the H group at 5% incline. We monitored exercise capacity and its response to training by measurements of VO2 max and blood lactate threshold (LT) every 3 mo throughout the training. The relative training intensity for the M animals, expressed by training speed as a percent of the running speed at LT, rose significantly as the animals aged (88% at 27 mo, 104% at 30 mo, 142% at 33 mo, and 325% at 36 mo). Similar results were seen with the H animals and when using VO2 max as a measure of exercise capacity. These results indicate that even in trained animals exercise capacity declines significantly in advanced age and stress the importance of measuring exercise ability at various time points throughout a prolonged training program.Supported by: NIH AG030423
Extensive type II muscle fiber atrophy in elderly women undergoing acute hip surgery after falling
Authors: Snijders Tim , Verdijk Lex B , Poeze Martijn , van Loon Luc J.C. 
Published: June 2021

BACKGROUNDAge‐related loss of skeletal muscle mass and strength increases the risk of falls and fractures, which is the most common cause of injury‐related death in persons above 75 years. This study compares muscle fiber characteristics of elderly women undergoing acute hip fracture surgery with those of healthy young and elderly controls.METHODSPercutaneous needle biopsies were collected from the vastus lateralis muscle in healthy young (21±1y) and older women (79±3y), and frail elderly women admitted for acute hip fracture surgery (83±6y). Immunohistochemical analyses were performed to assess muscle fiber size and satellite cell (SC) content in a fiber type‐specific manner.RESULTSType II muscle fiber size in both the healthy and frail elderly were smaller when compared with the young. Frail elderly showed a higher degree of muscle fiber atrophy and lower SC content when compared with healthy elderly, with differences being most prominent in type II muscle fibers.CONCLUSIONElderly at risk of falling show extensive type II muscle fiber atrophy and a decline in SC content when compared with age‐matched controls. Elderly at risk of falls and fractures may be identified by such muscle characteristics.
Contribution of group III and IV muscle afferents to ventilatory control during submaximal exercise in heart failure
Authors: Olson Thomas P , Joyner Michael J , Eisenach John H , Curry Timothy B , Johnson Bruce D 
Published: June 2021

BackgroundHeart failure (HF) causes abnormal ventilatory responses to exercise which are inked to poor prognosis. We examined the impact of blocking fine afferents from locomotor muscles on exercise ventilatory efficiency in HF.Methods9 HF patients (60±6yrs, LVEF 27±6%) and 9 healthy controls (63±7yrs) underwent two 5 min cycling sessions at 65% peak workload with and without intrathecal fentanyl. VO2, VCO2, VE, breathing frequency (fb), tidal volume (VT), and chemoreceptor sensitivity (CO2 rebreathe) were measured.ResultsFentanyl did not influence exercise VO2 in either group (HF=1.5±0.3 vs 1.5±0.3 L/min, control=1.7±0.4 vs 1.7±0.5 L/min). VE was lower with fentanyl in HF but not control (−12.3±7.1 vs 0.8±6.2%, p<0.001) due to lower fb (−10.5±4.6 vs 0.5±7.1%, p<0.01) with no change in VT (−1.2±9.4 vs 0.4±5.7%, p=0.67). VE/VCO2 improved during exercise with fentanyl in HF but not in controls (−14.8±7.1 vs ‐ 0.5±7.0, p<0.01). Fentanyl did not influence chemoreceptor sensitivity in either group.ConclusionBlocking group III and IV afferent feedback from the locomotor muscles during exercise improves ventilatory efficiency in HF. NIH/NCRR grant KL2‐RR024151.
Genistein represses invasion in an in vitro colon cancer metastasis model by transcriptionally upregulating metastasis repressor NDRG1
Authors: Li Qian , Chen Hong 
Published: June 2021

Cancer metastasis accounts for most cancer deaths. Genistein, a biologically active soy isoflavone, has been indicated as an inhibitor of cancer progression. In this study, we tested our hypothesis that genistein can repress colon cancer metastasis in vitro by modifying the expression of metastasis suppressor NDRG1. Cell models SW480 and SW620 which are poorly and highly metastatic human colon cancer cell lines respectively, were used. Genistein treatment reduced the proliferation and wound healing ability of both cell lines. Interestingly, genistein specifically increased the adhesion of the metastatic cell line SW620 and inhibited the migration of SW620. Moreover, genistein increased the mRNA expression of NDRG1 in both cell lines. The low NDRG1 gene expression in SW620 compared to that in SW480 is associated with altered chromatin configuration of the gene. In conclusion, genistein treatment increased expression of several genes responsible for metastasis repression in SW620. Future research will focus on illustrating the epigenetic mechanisms underlining the metastasis inhibiting effects by genistein.Grant Funding Source : University of Illinois at Urbana‐Champaign
Validating sugar‐sweetened beverage intake and adiposity among African‐American and White adults in a doubly labeled water study
Authors: Emond Jennifer A. , Patterson Ruth E , Jardack Patricia M , Arab Lenore 
Published: June 2021

Evidence is mixed regarding sugar‐sweetened beverage (SSB) intake and adiposity among adults. To look at the effect of reporting bias, we compared SSB intake and overweight/obese status (BMI ≥25 kg/m2) among adults in a dietary assessment and doubly labeled water study (n=250). Four web‐based, 24‐hour recalls assessed dietary intake. SSB intake was categorized as none, 1–99 kcals/day, or >99 kcals/day; 99 kcals/day was median SSB intake among consumers. Logistic regression models, adjusted for total caloric intake, age, race, education and diet quality, compared SSB intake to overweight/obese status. We repeated analyses in a subset of “true reporters”: those with self‐reported total caloric intake within 25% of total energy expenditure per doubly labeled water (n=108). One‐half of participants were overweight/obese; more overweight/obese participants drank SSB than normal weight participants (69% vs. 47%; p<0.001). Intake of other beverages did not differ by adiposity. Compared to no intake, SSB intake up to the median doubled the risk of being overweight/obese (OR: 2.1, 95% CI: 1.0–4.3; p=0.046), and SSB intake over the median more than doubled the risk (OR: 2.6, 95% CI: 1.2–6.0; p=0.018). When limited to true reporters, SSB intake significantly increased the risk of being overweight/obese by nearly 4 fold. Results support that SSB consumption increases the risk of being overweight/obese among adults. This funding for this project was provided by the National Institutes of Health grant R01CA105048, as well as training grant T32 GM084896.Grant Funding Source: Training grant T32 GM084896
Coffee consumption and risk of chronic disease in the European Prospective Investigation into Cancer and Nutrition (EPIC)‐Germany study
Authors: Floegel Anna , Pischon Tobias , Bergmann Manuela M , Teucher Birgit , Kaaks Rudolf , Boeing Heiner 
Published: June 2021

Early studies suggested that coffee consumption may increase risk of chronic disease. We investigated prospectively the association between coffee consumption and risk of chronic disease (type 2 diabetes, cardiovascular disease and cancer) in 42659 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)‐Germany study. Coffee consumption was assessed by self‐administered food frequency questionnaire at baseline and incident cases of chronic disease were identified and medically verified during follow‐up. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariate Cox proportional hazard regression. During 8.9 years of follow‐up, we observed 1432 cases of type 2 diabetes, 704 cases of cardiovascular disease, and 1801 cancer cases as first qualifying event. Coffee consumption was not associated with the overall risk of chronic disease (≥4 cups/d compared to <1 cup/d, HR: 0.94; 95% CI: 0.84–1.05). We observed an inverse association between coffee consumption and type 2 diabetes risk (≥4 cups/d compared to <1 cup/d: HR: 0.77, 95% CI: 0.63–0.94) and no association with risk of cardiovascular disease and cancer (≥4 cups/d compared to <1 cup/d: HR: 1.10, 95% CI: 0.84–1.44; and HR: 0.97; 95% CI: 0.83–1.14, respectively). Our data indicate that coffee consumption does not increase risk of chronic disease, but may be linked to lower risk of type 2 diabetes.Grant Funding Source : Federal Ministry of Science, Germany (grant No. 01 EA 9401), the European Union (grant No. SOC 95 201408 05F02), and the German Cancer Aid (grant No. 70‐2201‐Bo2)
Synergistic Inhibition of Lung Cancer Cell Growth by Nobiletin and Atorvastatin in Combination
Authors: Charoensinphon Noppawat , Zheng Jinkai , Qiu Peiju , Ngauv Perline , Xiao Hang 
Published: June 2021

Combination of different bioactive agents may produce enhanced inhibitory effects on cancer cells due to their synergistic interactions. We studied combination of nobiletin (NBT, a citrus flavonoid) and atorvastatin (ATST, a cholesterol‐lowering drug) in 3 human lung cancer cells. NBT/ATST co‐treatments at low doses produced much stronger inhibitory effects on all three cancer cells in comparison to those produced by NBT or ATST alone at higher doses. Isobologram analysis confirmed NBT/ATST combinations produced strong synergistic inhibition on lung cancer cells. Flow cytometry analysis showed NBT/ATST co‐treatments for 24 hrs induced G0/G1 cell cycle arrest, while the prolonged co‐treatments for 48 hrs caused extensive apoptosis. Immunoblotting showed NBT/ATST co‐treatments activated caspase‐3 and cleavage of PARP, increased levels of p21 (Cip1/Waf1) and p27 (Kip1), while decreased expression levels of Cdk‐2, Cdk‐4, Cdk‐6, Cyclin D1, hyper‐p‐Rb, and Mcl‐1. Expression levels of both EGFR and p‐EGFR (Tyr1068) in plasma membrane were decreased by NBT/ATST co‐treatment. qRT‐PCR assay showed that NBT/ATST co‐treatments profoundly modulated oncoginic miRNA (e.g., mir‐7) profile in lung cancer cells. Overall, our results demonstrated strong synergy between NBT and ATST in inhibiting human lung cancer cell growth, which warrants future investigation on the in vivo efficacy of NBT/ATST combination.Grant Funding Source: NIH: CA139174, AICR: 10A044
Nutrient biomarker patterns and rates of cognitive decline in dementia‐free elders
Authors: Bowman Gene L. , Quinn Joseph F. , Kaye Jeffrey A. , Shannon Jackilen 
Published: June 2021

BackgroundWe previously identified three distinct nutrient biomarker patterns associated with both psychometric and neuroimaging indices in a cross‐sectional analysis. The objective of this study was to examine the relationship between the nutrient biomarker patterns and cognitive decline over 2 years.MethodsThirty biological markers of diet were assayed in plasma drawn from 104 dementia‐free participants of the Oregon Brain Aging Study. Principal component analysis constructed 8 distinct nutrient biomarker patterns. A linear regression model was used to examine the change in the Clinical Dementia Rating ‐ sum of box score over two years explained by the nutrient biomarker patterns.ResultsMean age was 87±10, 62% are female, and 10% are carrying the ApoEe4 allele. Two distinct nutrient biomarker patterns were associated with rates of cognitive decline: a vitamin pattern high in vitamins B, C, E and D (p=0.001) and a high trans fat pattern (p<0.001) associated with less and more decline over two years, respectively. These findings were independent of age, gender, education years, ApoEe4 carrier status and vascular risk factors.ConclusionA nutrient biomarker pattern high in specific vitamins and low in trans‐fat may offer a prudent profile for promoting cognitive health in older populations. Funding: NIH/NCCAM AT004777 (GLB), NIH/NIA AG08017 (JAK), NIH/NCRR UL1 RR024140Grant Funding Source : NIH AT004777
Early Obesity Prevention: A Randomized Trial of a Practice‐Based Intervention in 0–24 Months Infants
Authors: Schroeder Natalia , Rushovich Berenice , Bartlett Edward , Gittelsohn Joel , Caballero Benjamin 
Published: June 2021

A pediatric office‐based intervention was implemented following a randomized, controlled design, aimed at improving child feeding practices, growth and ultimately reducing risk for overweight and obesity later in life. Educational materials on feeding and physical activity called Growing Leaps and Bounds was delivered by the health care provider during each well‐baby clinic visit. A total of 232 infants at 4 clinics (2 urban, 2 suburban), followed for 24 months completed the study. The intervention (I) group offered significantly less soda (p=0.006), sweetened tea (p=0.01), punch (p=0.02) or cow's milk (p=0.001) to infants compared to the control (C) group. I group delayed introduction of drink/food other than breast milk (p<0.05). Furthermore, parents in I group had higher perceived parental monitoring (p=0.05) and restriction (p=0.01) on infant feeding. While I group exhibited at baseline more adverse socioeconomic indicators than the C group, growth trajectory or body size indices did not significantly differ between the groups at the end of the follow‐up period. Education provided by health care providers may help modify parental behaviors related to child feeding and increase parental sense of responsibility toward child eating behaviors.Funded by the Dannon Institute
Intestinal Effects of Alanyl‐Glutamine Dipeptide‐Supplemented Diet in a Mouse Model of DSS‐Induced Colitis
Authors: Benton Shana , Hao Li , Merlin Didier , Jones Dean P. , Ziegler Thomas R. 
Published: June 2021

Enteral and parenteral glutamine administration has cytoprotective effects in animal models of gut injury. We investigated intestinal effects of oral diet supplemented with alanyl‐glutamine dipeptide (AG) in dextran sulfate sodium (DSS)‐induced colitis in mice.MethodsC57BL/6 mice were given 3.5% DSS in water and concomitantly pair‐fed iso‐N oral diets without AG (DSS) or with AG supplementation (AG‐DSS). Control mice did not receive DSS or AG. Mucosal injury scores, myeloperoxidase (MPO) activity, TNF‐α and IL‐6 mRNA (qPCR) and GSH/GSSG redox status were determined in jejunum, ileum and colon after 7 days; clinical status was assessed daily.ResultsFood intake was similar in all groups. DSS‐treated mice had weight loss, bloody diarrhea, and increased small bowel and colonic MPO activity vs controls regardless of diet (P <0.05). The AG‐DSS group exhibited greater histologic injury in both ileum and colon vs the DSS and control groups (P<0.05). Colonic TNF‐α mRNA was increased in the DSS group vs the AG‐DSS and control groups (P<0.05). IL‐6 mRNA and GSH/GSSG redox in jejunum, ileum and colon was similar in all 3 groups.ConclusionDietary supplementation with AG increased histologic gut injury and decreased colonic TNF‐α in this model of colitis. Supported by NIH grants K24 RR023356 and T32 DK007298.