bluuebunny/crossref_metadata_2025_split huggingface dataset:
C‐Abl Inhibition Exacerbates Mechanical Ventilation‐Induced Lung Injury In A Murine Model
Authors: Sammani Saad , Letsiou Eleftheria , Moreno- Liliana , Camp Sara M , Chiang Eddie T , Dudek Steven M , Garcia Joe G 
Published: June 2021

Endothelial cytoskeleton is a contractile structure responsible for cellular responses to external stimuli and mechanical stress. Nonmuscle myosin light chain kinase (nmMLCK), a critical actin‐binding protein is required for trafficking of inflammatory cellsand alterations in permeability. c‐Abl kinase plays an essential role in barrier regulation via posttranslational modification of nmMLCK. Abl tyrosine kinase phosphorylates nmMLCK and regulates endothelial barrier function. We hypothesized that tyrosine kinase inhibitor imatinib, an anticancer agent, can exacerbate lung injury induced by mechanical ventilation (MV). To explore the role of c‐Abl in lung injury in vivo, mice were tested in our ventilation‐induced acute lung injury (VILI) model after imatinib. Mice were harvested 4h after MV. Imatinib significantly increased bronchoalveolar lavage protein levels (825ug/ml) and total inflammatory cell counts (1.07 × 10□) compared to sham (571ug/ml, 0.75 × 10μ) (p<0.05). These preliminary results indicate that imatinib exacerbates VILI‐injury, likely via c‐Abl blockade. These studies have clinical relevance given the extensive use of imatinib as an anticancer agent and support an important functional role for c‐Abl in lung permeabilityFunded by: NIH grant: P01 HL58064
Influence of a short‐term increase in pressure, with and without recovery, on flow‐induced dilation in aged soleus muscle feed arteries (SFA)
Authors: Seawright John , Woodman Christopher R. 
Published: June 2021

We tested the hypothesis that a short‐term increase in intraluminal pressure, to mimic a bout of exercise, would attenuate age‐induced impairments in flow‐induced dilation in SFA and that improved endothelial function would persist after a 2 h recovery period. SFA were isolated from young (4 mo) and old (24 mo) Fischer 344 rats. SFA were cannulated and pressurized at 90 (p90) or 130 (p130) cm H2O for 1 h. At the end of the 1 h treatment period, p130 SFA were lowered to 90 cm H2O and flow‐induced dilation was assessed. In a separate group of SFA, pressure was raised to 130 cm H2O for 1 h and subsequently lowered to 90 cm H2O for 2 h. Flow‐induced dilation was significantly blunted in old SFA relative to young SFA. Pre‐treatment with increased pressure for 1 h improved flow‐induced dilation in old (not young) SFA. The beneficial effect of pressure was not apparent after 2 h recovery. To determine the role of nitric oxide (NO) in pressure treated SFA, flow‐induced dilation was assessed in the presence of a NOS inhibitor (L‐NNA). Results indicate that the beneficial effect of pressure on flow‐induced dilation in old SFA was abolished in the presence of L‐NNA. These results indicate that a short‐term increase in intraluminal pressure, to mimic a bout of exercise, improves NO‐mediated endothelium‐dependent dilation in old SFA; however, the beneficial effect of pressure is not apparent after 2 h recovery.Research supported by AHA grant 4150031 (CRW), and a Huffines Institute of Sports Medicine Graduate Student Research Grant (JWS).
STUDY OF THE EFFECT OF CHRONIC CHOLINERGIC STIMULATION WITH PYRIDOSTIGMINE BROMIDE ON CARDIOVASCULAR AUTONOMIC CONTROL IN SPONTANEOUSLY HYPERTENSIVE RATS (SHR)
Authors: BLANCO JOAO HENRIQUE DUTRA , SOUZA HUGO CELSO DUTRA 
Published: June 2021

We investigated in spontaneously hypertensive rats (SHR) the effect of chronic inhibition of acetylcholinesterase (AChE) with pyridostigmine bromide (PYR) on the autonomic cardiovascular control. Fourteen male SHR (22 weeks old) were divided into 2 groups: SHR‐Control and SHR‐PYR (treated with PYR dissolved in drinking water (~30mg/Kg/day) for 2 weeks). The autonomic control was investigated by using different approaches: 1) double blockade with methylatropine and propranolol, 2) baroreflex sensibility (BRS) with phenylephrine and nitroprussite and 3) autonomic modulation of heart rate variability (HRV) and the systolic blood pressure variability (SBPV).Treatment with PYR reduced the mean blood pressure (BP) and heart rate (HR) compared to control animals (141±3 vs. 151±2 mmHg and 322±6 vs. 355±5 bpm). Regarding the autonomic control, treatment with PYR promoted the following effects; increase in cardiac vagal tone (72±10 vs. 36±7 bpm); increase in BRS for the tachycardic responses (2.74±0.15 vs. 0.81±0.11 bpm/mmHg); and reduction in low frequency oscillations of SBPV (3±0.4 vs. 5.4±0.4 mmHg2).Our results show that treatment with PYR in hypertensive rats promote reduction in BP and HR associated with improvement of cardiac autonomic control assessed by different approaches.Grants: FAPESP 2011/22513‐4.
Isolation and Surface Characterization of Mesenchymal Stem Cells(MSCs) Derived From Term Human Amnion
Authors: Ren Yuexin , Stabila Joan P , Kurihara Itsuka , Morgan Jeffrey Y , Aaron Roy K , Padbury James 
Published: June 2021

ObjectiveArticular cartilage damage has a very low spontaneous healing capacity. Emerging evidence suggests human placental membrane is a valuable source of MSCs for cell‐based therapy to promote articular cartilage repair. However, the identification of MSC has been hampered. Thus there is a clear need to develop strategies leading to the identification of potential MSC markers. The objective of this study was to isolate and characterize the cell populations derived from term pregnancy human amnion.MethodsCells were isolated from amnion membranes from patients at gestational weeks 39±1. Flow cytometry analysis was performed with the cells. Direct conjugated Ab used for flow cytometry included anti‐CD44‐FITC, CD73‐FITC, CD105‐FITC, CD45‐PerCP, CD90‐PerCP, CD11b‐PE, CD29‐PE, CD34‐PE. Analysis was performed with FlowJo software.ResultsThe positive markers in isolated cell populations on Day 0 were CD14, CD11b, CD29, CD44, CD45, CD90, CD105. After 10 days culturing in expansion medium, the macrophage marker CD14 disappeared and mesenchymal stem cell markers (CD29, CD44, CD90, CD73, CD105) were demonstrated increased expression levels. Throughout, the cells were negative for markers of developmental stages of blood cells(CD11b, CD45).ConclusionOur results indicate that MSCs can be isolated from the human term placental membranes. The human amniotic MSCs maintained a marker profile similar to the mesenchymal progenitors and could be used for studies as an alternative source of MSCs for further application in cell‐based therapies.
Voluntary wheel‐running improves metabolic flexibility in the liver
Authors: Kearney Monica L. , Morris E. Matthew , Meers Grace M. , Fletcher Justin A. , Thyfault John P. 
Published: June 2021

Hepatic metabolic flexibility, the capacity to change substrate utilization, may be important for protection against hepatic steatosis. To examine whether increased physical activity improves substrate switching in liver mitochondria, age‐matched male Sprague‐Dawley rats underwent 4 weeks of voluntary wheel‐running (WR; n=4) or remained sedentary (SED; n=4) prior to sacrifice at 16 weeks. At sacrifice, there was a trend towards lower body weight in WR compared to SED, but food intake and intake per body weight were not different between groups over the 4 weeks. Isolated hepatic mitochondria were analyzed for fatty acid oxidation (FAO) with and without addition of 1 mM pyruvate, and pyruvate oxidation (PyvOx) with and without addition of 200 μM palmitate. Complete FAO (14C palmitate to 14CO2) was higher in WR compared to SED (4.29 ± 0.05 vs. 3.01 ± 0.11 nmol/g/h; p < 0.05), and the amount of FAO inhibited by pyruvate was 2 fold higher in WR vs. SED (1.74 ± 0.19 vs.0.82 ± 0.23 nmol/g/h; p < 0.05). Furthermore, the amount of complete PyvOx (14C pyruvate to 14CO2) inhibited by palmitate in mitochondria was 25% higher in WR compared to SED (41.57 ± 0.04 vs.31.24 ± 0.09 nmol/g/h; p < 0.05). Thus, higher daily physical activity results in greater substrate‐switching and metabolic flexibility in hepatic mitochondria.Support: NIH R01DK088940
Skeletal muscle as a possible compartment for the sequestering of Doxorubicin following administration
Authors: Fabris Sergio Antonio , Chenard Pamela , MacLean David 
Published: June 2021

Doxorubicin (DOX) is an anti‐cancer chemotherapeutic and although widely used, its accumulation over time in skeletal muscle tissue has attracted little attention. The purpose of this research was to study intracellular DOX concentrations in skeletal muscle following its administration in the rat. A bolus injection of 1.5 and 4.5 mg/kg of DOX was administered intraperitoneally in Sprague Dawley rats, and medial gastrocnemius samples were collected 24 and 96 hrs post injection. Intramuscular DOX concentrations were elevated (P<0.05) as compared to control at all time points. Following the 1.5 and 4.5 mg/kg dose, intramuscular concentrations decreased (P<0.05) from 0.24±0.05 and 0.83±0.18 nmol/g at 24 hrs to 0.04±0.01 and 0.40±0.10 nmol/g at 96 hrs, respectively. Although there was a decrease in the intramuscular concentration of DOX over time, these levels remained higher (P<0.05) in the 4.5 mg/kg rats as compared to those administered the 1.5 mg/kg dose. Interestingly, at the lower dose, the intramuscular DOX levels had decreased 83% between 24–96 hrs, while at the larger dose this decrease was only 52%. These data clearly demonstrate that DOX accumulates in skeletal muscle in a dose dependant manner. Furthermore, it appears that the rate of removal or degradation of the intramuscular DOX is slower at increasing doses. These findings have clinical implications as skeletal muscle may be an important compartment for the sequestering of DOX from the circulation, hence limiting its therapeutic impact. This intramuscular accumulation may also have an effect on long‐term function as its metabolite has been shown to be cytotoxic.Supported by NSERC.
Mid‐Career Adventure: Making a Successful Transition
Authors: Koen Deb 
Published: June 2021

“Life is either a daring adventure or nothing.” Helen KellerWhether your mid‐career transition is driven by a deeper calling, a negative situation, or simply curiosity about what else you might become, why not make your transition an adventure? Although most people change careers—some many times‐‐ over the course of their professional lives, the path forward is not always easy or obvious.Transitions can be significantly enhanced with a sound strategy and a spirit of adventure. If you're considering a dramatic change or even dabbling in minor adjustments, this talk will offer a framework for successful transition.These success strategies will allow you to immediately begin to: discover your motivators, generate options within the realm of science and beyond, overcome barriers, and develop a focused plan for your future.
Maternal DHA supplementation during pregnancy and plasma lipids and glucose levels in offspring at age 4y: follow‐up of a randomized controlled trial
Authors: Gutierrez‐Gomez Yareni Yunuen , Ramakrishnan Usha , Stein Aryeh D. , Martorell Reynaldo , Aguilar‐Salinas Carlos , Romieu Isabell , Rivera Juan A. 
Published: June 2021

Little is known about the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring lipid and glucose metabolism. We investigated the effect of maternal DHA supplementation during pregnancy on offspring plasma lipid and glucose levels at age 4 y. In a double‐blind, randomized, controlled trial conducted in Mexico, pregnant women were supplemented daily with 400 mg DHA or placebo from 18–22 wk gestation to parturition. Offspring of the women who participated in this study are being followed; at age 4 y non‐fasting blood samples, were obtained from 524 children (53.9% of the birth cohort). We assessed total cholesterol (TC; mean ±SD 157.9 ±25.3mg/dl); LDL‐C (83.0 ±21.9mg/dl); HDL‐C (51.7 ±10.1mg/dl); Apo B (76.9 ±15.2mg/dl); triglycerides (122.1 ±67.4mg/dl); glucose (93.7 ±10.9mg/dl) and insulin (9.7 ±11.2μU/ml). Between‐group differences (DHA ‐ placebo), adjusted for maternal height and time since last food intake, were: TC, 1.73 mg/dl (95% CI −2.63, 6.09); LDL‐C, 1.62 mg/dl (0.24, 1.42); HDL‐C, 0.66 mg/dl (−1.07, 2.39); Apo B, −0.15 mg/dl (−2.78, 2.48); triglycerides −0.15 mg/dl (−11.50, 11.21); glucose −0.99 mg/dl (−2.86, 0.88); insulin −0.18 μU/ml (− 2.08, 1.7). In this study, prenatal DHA supplementation did not impact on lipids and glucose markers in early childhood.Funded by NIH (HD043099)
Leptin and resistin are influenced by increased body fat measurements in pregnant women
Authors: Ozias Marlies K , Li Shengqi , Lin Ping‐Chang , Schmitt Allan , Hull Holly R , Carlson Susan E 
Published: June 2021

Our objective was to determine if adipokine concentrations were associated with total body fat, subcutaneous (SF) and visceral abdominal fat (VF) in obese (O) and normal weight (N) pregnant women. Plasma adipokines (leptin, adiponectin, visfatin, and resistin) were measured in 5 O and 9 N pregnant women (no pre‐eclampsia or GDM) after 35 wks gestation by EIA (Alpco Diagnostics; Phoenix Pharmaceuticals). We grouped women based on subject‐reported pre‐pregnancy weight and height. Total body fat was measured 2‐wks postpartum by iDXA (GE Healthcare). SF and VF were measured with Image J software from MRI (Siemens Skyra 3T) abdominal axial scans (5.0mm; 5.0mm gap) of vertebral L2‐S3. Statistical analyses involved t‐tests between groups and simple linear regression to compare adiposity measurements to adipokine concentrations. Leptin increased in O vs N (74 vs. 31 ng/mL, P < 0.001) and was associated with total body fat mass (r = 0.843; P < 0.001), SF (r = 0.649; P = 0.012) and VF (r = 0.618; P = 0.019). Resistin was only associated with SF (r = 0.538; P = 0.038). O women had significantly more SF (2137 vs. 706 g; P = 0.041) but not VF (290 vs. 103 g; P = 0.117) compared to N women. In pregnancy, elevated leptin concentration was associated with all measures of adiposity while resistin was only associated with SF. These findings suggest that increased leptin may be an accurate biomarker of adiposity during pregnancy.Grant Funding Source: Sam E. and Mary F. Roberts Endowment, NICHD HD02528, NIH S10 RR029577 and UL1 TR000001
Salt induced cardiac hypertrophy is blood pressure independent and prevented by Losartan and N‐acetylcysteine
Authors: Katayama Isis AKemi , Pereira Rafael Canavel , Shimizu Maria Heloísa Massola , Heimann Joel Claudio 
Published: June 2021

ObjectiveTo evaluate the mechanisms of left (LV) and right (RV) ventricular hypertrophy induced by high salt intake.MethodsWistar rats were fed normal (NS1.3% NaCl) or high (HS 8%) salt diet since weaning. From the 7th week of age, 3 HS subgroups received hydralazine, losartan or N‐acetylcysteine (HZ 15 and LOS 20mg/kg/day and NAC 600mg/l). Tail blood pressure (BP), food intake (FI), cardiac mass to tibial length ratio (CM/TL), cardiomyocyte transverse diameter (TD) in both ventricles and myocardial TBARS were measured.Results (n=8/group):

NS
HS
HS+HZ
HS+LOS
HS+NAC

BP (mmHg)
110.7± 1.6a
143.1± 4.0b
116.4± 1.8a
116.5± 1.6a
166.8± 1.6c

FI (g/day)
16.6±1.85 a
15.7±0.91 a
14.3±0.59 a
16.5±0.98 a
23.7±0.63 a

CM/TL (g/cm)
0.34±0.01a
0.51±0.02b
0.47±0.02b
0.38±0.01a
0.44±0.00c

TD – LV (μm)
12.5±0.47a
19.6±0.44b
18.9±0.76b
13.2±0.33a
15.9±0.75c

TD – RV (μm)
11.8±0.32a
17.7±0.56b
16.4±0.71b
11.9±0.45a
12.8±0.41a

TBARS (nmol/mg/ml)
0.78±0.27 a
2.57±0.38 b
2.75±0.75 b
2.65±0.32 b
0.89±0.09 a

Data are reported as mean±SEM. Means in row with superscripts without a common letter differ, P<0.05

ConclusionsIn Wistar rats, LOS prevented cardiac hypertrophy induced by high salt intake. It can be speculated that this result is an AT1 receptor‐dependent mechanism. However, NAC partially prevented the cardiac hypertrophy, suggesting that oxidative stress also could be involved on this process.Supported by FAPESP and CNPq.
Diverse Effects of Aging on the Cardiac Response in Pathological Left Ventricular Remodeling and Dysfunction
Authors: de Boer Martine , van Deel Elza D. , de Kleijnen Marion , Hoeijmakers Jan H.J. , Duncker Dirk J. 
Published: June 2021

The aging heart undergoes structural and functional changes that are reminiscent of the failing heart, and which thus may increase cardiac vulnerability to develop heart failure. To test this hypothesis, we subjected mice to pressure overload by transverse aortic constriction (TAC) or myocardial infarction (MI) at 3, 12 and 24 months of age. Eight weeks after TAC or MI, left ventricular (LV) geometry and function were measured. Aging mildly affected cardiac geometry and function in sham operated animals. TAC produced marked LV hypertrophy, cardiac dysfunction, pulmonary congestion and right ventricular (RV) hypertrophy in all age groups. MI produced LV dilation, cardiac dysfunction and LV and RV hypertrophy in all age groups. Interestingly, the hypertrophic responses to TAC and MI were diminished with aging, but whereas the blunted hypertrophic response in TAC was associated with aggravated LV dysfunction, LV function tended to improve in MI. Thus, aging aggravated the TAC‐induced decrease in LV dP/dtP40 and LV dP/dtmin and the increase in lung fluid and RV weight in the 24 vs. 3 months old mice. In contrast, MI‐induced diastolic dysfunction was slightly blunted with aging as demonstrated by decreases in tau and LV end diastolic pressure in the 24 vs. 3 months old mice. These observations indicate that the effects of aging on the cardiac response to hemodynamic overload depend critically on the underlying pathology.Supported by a NHF Grant 2007B024
VPT‐60: A novel approach to monitoring peripheral nerve sensitivity
Authors: Blackburn Mollie , Gibson Janelle , Breen Paul , Latman N. S. 
Published: June 2021

Peripheral nerve sensitivity (PNS) can be used as an indicator of nerve loss or damage known as peripheral neuropathy. Because peripheral neuropathy can result in morbidity and mortality, accurate monitoring of PNS is imperative.A review of the literature has shown that variables such as age, sex, compression force and temperature can effect PNS. Neither of the two clinical reference standards [Semmes‐Weinstein Monofilaments (SWM) or Bio‐Thesiometer (BT)] take these variables into account in determining PNS.We developed a novel instrument, VPT‐60, that measures PNS, temperature and compression force of a digit. It can vary the frequency of vibration and the rate of amplitude change among other variables.The correlation of these variables with PNS was analyzed in 41 subjects that exhibited a wide range of characteristics. We found a statistically significant correlation coefficient between VPT‐60 PNS and age [0.52 (p=0.001)]; sex [0.33 (p=0.03)]; finger weight [−0.045 (p=0.005)]; and finger temperature [0.34 (p=0.03)]. While the VPT‐60 had a significant correlation with both the SWM (0.75) and the BT (0.86), the BT correlation with SWM was only 0.51. At 60 Hz vibration, the VPT‐60 had a higher correlation with SWM than did the BT at 120 Hz.In this study, the VPT‐60 appeared to provide a better approach to determining peripheral nerve sensitivity and the factors that effect it than the SWM or BT.
The Sydney Diet Heart Study: a randomised controlled trial of linoleic acid for secondary prevention of coronary heart disease and death
Authors: Ramsden Christopher E , Zamora Daisy , Faurot Kim , Majchrzak Sharon , Hibbeln Joseph 
Published: June 2021

ObjectiveTo evaluate the effectiveness of replacing saturated fat (SFA) with omega‐6 linoleic acid (LA) for the secondary prevention of coronary heart disease (CHD) and death.BackgroundAdvice to substitute polyunsaturated fats (PUFAs) for SFA is a cornerstone of dietary guidelines. However, clinical CHD benefits of the most abundant PUFA, omega‐6 LA have not been established. A complete analysis of the effects of LA on CHD and CVD mortality has not previously been possible due to missing data from the Sydney Diet Heart Study (SDHS). We recovered the original SDHS dataset to fill two key evidence gaps by (1) reporting unpublished CHD and CVD mortality outcomes, and (2) updating our incomplete 2010 meta‐analysis of LA intervention trials.DesignRandomised controlled trial in 458 men with CHD.InterventionsThe intervention group replaced SFA with LA from safflower oil and safflower oil polyunsaturated margarine. The control group continued their habitual diet.ResultsThe intervention group had higher all‐cause (HR 1.62; 95%CI 1.00–2.64; p=0.051), CVD (HR 1.70; 95%CI 1.03–2.80; p=0.037) and CHD mortality (HR 1.74; 95%CI 1.04–2.92; p=0.036). An updated meta‐analysis of LA intervention trials showed concordant unfavorable effects for CHD and CVD death.ConclusionsSubstituting LA in place of SFA increased all‐cause, CVD and CHD mortality. Advice to increase LA or unspecified PUFAs merits reconsideration.Support:NIAAA
Dietary carotenoids may reduce testicular steroidogenesis through HMG‐CoA reductase in mice with altered carotenoid metabolism
Authors: Smith Josh , Ford Nikki , Clinton Steven K , Erdman John W 
Published: June 2021

Higher serum levels of lycopene are inversely associated with prostate cancer incidence. Previous work in our lab has demonstrated that, in mice lacking carotene‐15,15′‐ monooxygenase (CMO1), dietary tomato powder or lycopene reduces testicular and serum testosterone levels. We hypothesized that lycopene may reduce testicular steroidogenesis through HMG‐CoA reductase (HMGCoAr). Nine‐ to twelve‐week‐old male wild‐type (WT), CMO1−/−, and carotene‐9′,10′‐monooxygenase knockout (CMO2−/−) mice were fed AIN‐93G‐based diets containing 10% tomato powder (TP), lycopene beadlets matched for lycopene content (LYC), or control diets for four days. We examined testicular mRNA and protein expression of canonical steroidogenic enzymes and found no alterations which explained the observed hormonal changes. However, protein levels of HMGCoAr were significantly decreased (p<0.05) in WT and CMO1−/− mice fed TP or LYC, but not in CMO2−/− mice. HMGCoAr mRNA expression was unaltered, suggesting that control is through a post‐transcriptional mechanism. We also examined mRNA expression of a testicular cholesterol acquisition mediator, SR‐B1, and found no changes. In summary, LYC and TP decreased testicular HMGCoAr protein levels in a CMO2‐ dependent manner, suggesting that metabolites of lycopene or other tomato carotenoids, produced by CMO2 cleavage, may mediate this effect.Grant Funding Source: NIH grant PHS‐1‐RO1 CA125384