bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of sex hormones on metabolic rate, ventilation and respiratory‐related upper airway muscle activities in female rats
Authors: Richardson Patrick A. , Fregosi Ralph F. , Hoyer Patricia B , Bailey E. Fiona 
Published: June 2021

We tested the hypothesis that changes in sex hormones in female rats resulting from ovarian failure induced by exposure to 4‐vinylcyclohexene diepoxide (VCD) alter metabolism, ventilation and respiratory‐related upper airway muscle activities.Two groups of Fischer‐344 female rats were used, one group injected daily with VCD, 80 mg/kg i.p. for 25 days (N=5), the other an age‐matched control group (N=5) injected daily with sesame oil. We obtained in‐vivo measures of VCO2/VO2, tidal volume (VT ) and breathing frequency (FR) using a sealed whole‐body plethysmography chamber. In the same animals, we recorded EMG activities of hyoglossus (HG) and genioglossus (GG) muscles and esophageal pressure (Pes) under urethane anesthesia in hyperoxia (FICO2=0) and hyperoxic hypercapnia (FICO2=0.03, 0.06, 0.09, 0.12 balance O2).Preliminary data reveal increased basal VO2, VCO2 and the ratio of VCO2/VO2 for VCD treated rats relative to age‐matched controls. Measures of ventilation and whole muscle EMG were comparable for the two groups in hyperoxia whereas VCD treated rats exhibited a trend toward higher VT and FR and greater average GG and HG EMG activities in hyperoxic hypercapnia relative to the age‐matched controls.These studies provide preliminary insights into metabolic rate, ventilation and respiratory‐related upper airway activities as a function of ovarian failure in age‐matched controls.
Renal damage in the non‐clipped kidney in two kidney one clip rat is most pronounced in the juxtamedullary cortex.
Authors: Skogstrand Trude , Hultström Michael , Iversen Bjarne Magnus 
Published: June 2021

Renal damage in old spontaneous hypertensive rats (SHR) was found to start in the juxtamedullary cortex (JMC) and extend towards the outer cortex (OC), with a clear difference in gene expression for the enzymes involved in collagen metabolism in the two compartments. In the present study we studied the progression of hypertensive renal damage in the non‐clipped kidney of two kidney, one clip (2k1c) rats, 6, 16 and 24 weeks after clipping. The mean arterial pressure was increased after 2‐4 weeks, and was 166±9 mmHg in the 2k1c group and 116±7 mmHg in the control group after 24 weeks. The 6 and 16 week group showed no histological damage, or up regulation of the mRNA expression of collagen type‐1‐A1 (col1a1), procollagen‐n‐ and c‐peptidase (n‐pep, c‐pep). At sacrifice the 24 week 2k1c group had a protenuria of 760±251 mg/mmol creatinine, higher than in the control group (92± 12 mg/mmol creatinine, p<0.05). The mRNA expression of col1a1 and n‐pep in the JMC in 2k1c was higher than in the OC, and higher than in the control group. We found no difference in the expression of c‐pep.In conclusion, it looks like our previous findings of a progression of renal damage from JMC towards OC in SHR, is a systematic feature of hypertensive renal damage. The increased expression of n‐pep may be an important mechanism in the increased collagen deposition.The study was funded by the University of Bergen and Helsevest, Norway
CARDIOVASCULAR EFFECTS OF ACETYLCHOLINE MICROINJECTED INTO THE LATERAL PERIAQUEDUCTAL GRAY AREA OF RATS.
Authors: Deolindo Milena vieira , Pelosi Gislaine , Correa Fernando Morgan de Aguiar 
Published: June 2021

INTRODUCTIONThe periaqueductal gray area (PAG) is a mesencephalic region that is involved in the modulation of cardiovascular changes associated with behavioural responses. Among the neurotransmitters present in the PAG, acetylcholine (Ach) is also known to be involved in central cardiovascular control. In the present study, we attempted the cardiovascular effects of the microinjection of Ach into the lateral portion of the PAG (lPAG) of rats.METHODSMale Wistar rats were used. Guide cannulas were implanted in the lPAG for drug injection and a polyethylene catheter was implanted in the femoral artery for arterial pressure (AP) and heart rate (HR) recording using a computerized acquisition system.RESULTSThe injection of different doses of Ach (27 and 81nmol/ 50nl) into the lPAG of unanaesthetized rats caused dose‐related depressor responses accompanied by bradycardia. However, the injection of different doses of Ach (27 and 81nmol/50nl) into the lPAG of anaesthetized rats caused dose‐related depressor responses accompanied by tachycardia.CONCLUSIONThe present results indicate that activation of cholinergic receptors within the lPAG can evoke cardiovascular responses of rats.FINANCIAL SUPPORTFapesp (07/50166‐1) and Fapesp (05/57227‐0)
Role of ghrelin in cell recovery following myelosuppressive chemotherapy
Authors: Fahim Mohamed Abdelmonem , Kataya Hazem , Karam Sherif , al‐Ramadi Basel 
Published: June 2021

Ghrelin is a peptide hormone produced by cells of the stomach in response to negative energy balance. Ghrelin promotes growth hormone secretion from the pituitary via binding to a G‐protein‐coupled growth hormone secretagogue receptor. Acumulating evidence has hinted that ghrelin may have diverse biological functions in different systems, including the immune system. Ghrelin receptors are known to be expressed on T cells and macrophages, and these cells have been shown to secrete ghrelin. In the current study, we assessed the influence of ghrelin on recovery of bone marrow‐derived cells following chemotherapy. C57BL/6 mice were given a high dose of either Doxorubicin (10 mg/kg, i.v.) or 5‐Fluorouracil (100 mg/kg, i.v.) with or without daily i.p. injections of ghrelin. WBC, RBC and platelets were substantially reduced by 4 days after administration of chemotherapy and began to recover by day 9. Ghrelin was administered i.p. in 3 different regimens: 4ng/kg body weight every 48 hours, 10 μg/kg body weight every 48 hours, and 20 μg/day given in twice daily injections for 5 consecutive days. The recovery of WBC, RBC and platelet counts was followed for up to 14 days post chemotherapy administration. The results showed that at the doses of ghrelin used, there was no difference in the rate of recovery of the three cell populations in mice co‐injected with 5‐FU and ghrelin.Supported by a grant from UAE University Research Affairs.
Inhaled nitric oxide improves left ventricular function during myocardial ischemia
Authors: Neye Nils , Habazettl Helmut , Plesnila Nick , Kuebler Wolfgang M. 
Published: June 2021

Inhaled nitric oxide (NOi) exerts extra‐pulmonary effects by formation of nitrite and/or S‐nitrosohemoglobin. Both release NO during hemoglobin desaturation, and may thus redistribute blood flow selectively to areas in need (Robin Hood Effect). Here, we studied the effects of NOi on left ventricular function and infarct size in a rat model of myocardial infarction (MI).MI was induced by occlusion of the left anterior descending (LAD) artery for 2 h. Rats were either sacrificed or reperfusion was re‐instated for 3 h. 50 ppm NOi was given during ischemia . Arterial pressure (AP), left ventricular pressure (LVP) and contractility (dp/dt) were measured, and infarct size and area at risk (AAR) were determined by methylene‐blue and tetrazolium red staining.After 2 h LAD occlusion, NOi had increased mean AP from 55.1±2.3 (in untreated controls) to 67.6±2.1 mmHg, systolic LVP from 66.3±2.8 to 80.2±2.6 mmHg, and dp/dt (max) from 1536±54 to 2287±62 mmHg/s (n=10 each, *p<0.05). NOi also reduced AAR from 39.7±1.8 to 28.7±0.9% of the left ventricle. After additional 3 h of reperfusion without NOi, mean AP, systolic LVP and dp/dt (max) were still higher in rats which had received NOi during ischemia as compared to controls, while infarct size was reduced from 24.7±2.5% to 17.4±0.3%.NOi improves left ventricular function during myocardial ischemia, presumably by selectively improving collateral blood flow to the AAR.
A role of PFKFB3/iPFK2 in the regulation of high fat diet‐induced inflammation and metabolic responses
Authors: Guo Xin , Li Honggui , Wu Chaodong 
Published: June 2021

Feeding of a high fat diet (HFD) is shown to induce inflammation and dysregulated metabolic homeostasis. Here we show that PFKFB3, a gene whose product controls glycolysis, plays a pivotal role in the regulation of HFD‐induced inflammatory and metabolic responses. Upon feeding a HFD, C57BL6 wild‐type mice exhibit a significant increase in body weight, which is associated with increased fat accumulation in both the liver and adipose tissue. This weight gain‐effect of HFD feeding is significantly lessened in mice that lack one allele of PFKFB3 (PFKFB3+/− mice). In addition, there are no increases in fat accumulation in both the liver and adipose tissue of HFD‐fed PFKFB3+/− mice. However, compared to HFD‐fed wild‐type mice, HFD‐fed PFKFB3+/− mice exhibited a greater increase in tumor necrosis factor α(TNFα) and interleukin 6 (IL6) expression in both the liver and adipose tissue, indicating elevated inflammation. Moreover, plasma levels of glucose in HFD‐fed PFKFB3+/− mice are much higher than those in HFD‐fed wild‐type control mice, which are accompanied by exacerbated glucose intolerance and insulin resistance. Together, these findings demonstrate that PFKFB3 is crucial for the regulation of HFD‐induced inflammation and dysregulated metabolic homeostasis. Approaches that stimulate PFKFB3 expression may be viable to prevent or treat diabetes.Grant Funding Sourcenone
Mediterranean diet, weight loss and features of the metabolic syndrome
Authors: Richard Caroline , Charest Amélie , Couture Patrick , Lamarche Benoît 
Published: June 2021

The objective of this study was to examine the efficacy of the Mediterranean diet (MedDiet) under optimally controlled conditions, with and without weight loss, on the cardiometabolic risk profile of male patients with the metabolic syndrome (MetS). Twenty‐six men aged between 24 to 62 years with the MetS (NCEP‐ATP III) consumed a North American control diet for 5 weeks followed by a 5‐week MedDiet, both under weight‐maintaining conditions. They then underwent a 20‐week weight loss phase, after which they consumed the weight stabilizing MedDiet for the second time. All foods were provided to participants during the isocaloric phases of the study. The MedDiet without weight loss decreased total plasma cholesterol (C), LDL‐C and the total/HDL‐C ratio by 7.1%, 9.3% and 6.5% respectively, compared to the control diet (all p<0.05). Body weight was reduced by 8.2% and waist circumference by 8.0 cm during the weight loss phase (p<0.001). The MedDiet with weight loss reduced systolic blood pressure (‐4.6%), diastolic blood pressure (‐9.5%), triglyceride (‐16%), apoB (‐10%) and fasting glucose (‐6.0%) compared to the control diet (all p<0.03).ConclusionThe MedDiet leads to significant changes in plasma cholesterol concentrations but weight loss appears to be required for the MedDiet to modify the cardiometabolic risk factors associated with the MetS. Financial support: Canadian Institutes for Health Research.
Instrumental variable analysis to adjust for non‐compliance to randomized dietary interventions: An application to protein intake and bone health in adults
Authors: Thorpe Matthew P , Layman Donald K , Evans Ellen M 
Published: June 2021

Non‐compliance in randomized controlled trials (RCT) dilutes estimated treatment efficacy under intent‐to‐treat analysis (ITT), producing an overly conservative statistic. ITT is preferred to as‐treated analysis, where treatment actually received is subject to confounding related to non‐compliance. Another approach, instrumental variable (IV) analysis, is gaining acceptance in clinical trial analysis but is not commonly applied to dietary interventions. We use a RCT of dietary protein and bone health to explore benefits and limitations of IV analysis. Patients (n = 73) were randomized to weight loss diets providing 1.4 (PRO) or 0.8 (CHO) g/kg·d protein. Compliance was monitored by weekly 3d weighed food records. Change in total hip bone mineral density (BMD) as a percent of baseline, measured by dual X‐ray absorptiometry, was compared at 1 year. IV analysis was applied using two‐stage least squares regression. Based on ITT analysis, random assignment to PRO (without respect to compliance) caused (B±SE) 1.36±0.59% (p=0.023) improvement in BMD compared to CHO. IV analysis estimated this value at 1.51±0.63% (p=0.019). Accounting for non‐compliance using an IV approach resulted in an 11% increase in estimated efficacy of treatment. IV analysis provides unbiased estimates of efficacy, corrected for non‐compliance, in the interpretation of RCTs. Discussion of logic and implementation of IV analysis follows.Grant Funding SourceIllinois Council on Food and Agricultural Research
Dietary Supplements Protect Retinal Pigment Epithelial Cells From Hyperglycemic Damage
Authors: Lin Dingbo , Zhang Yunong , Medeiros Denis M 
Published: June 2021

ObjectiveTo determine the protective effects of wolfberry on hyperglycemic damage in retinal pigment epithelial cells.MethodsHuman retinal pigment epithelial ARPE‐19 cells were treated with 36 mM glucose for 60 hrs, with or without 1 mg/mL crude wolfberry extracts. PKCgamma activation was determined by enzyme activity assay. Gap junction activity was determined by scrape loading/dye transfer assay. Western blotting was used to determined activation of AMP‐activated protein kinase (AMPK), acetyl‐CoA carboxylase (ACC), and apoptosis‐inducing factor (AIF).ResultsHigh glucose‐activated PKCgamma phosphorylated Connexin 50 (Cx50) and Cx57 on serines, and subsequently inhibited gap junction activity. Wolfberry extracts abolished the effects of high glucose on PKCgamma activation. Application of wolfberry extracts abolished the inhibitory effect of high glucose on AMPK activation, completely restored ACC phosphorylation by AMPK, and inhibited AIF translocation out of mitochondria.ConclusionsHigh glucose‐induced AIF‐dependent apoptosis would be protected by application of wolfberry extracts through restoration of cellular gap junctional communication and rebalance of cellular energy homeostasis.
Variations in Dietary Copper Alter Physiological and Behavioral Function
Authors: Bousquet‐Moore Danielle , Eipper Betty , Prohaska Joseph , Mains Richard 
Published: June 2021

Post‐translational α‐amidation by peptidyglycine α‐amidating monooxygenase (PAM), a Cu‐dependent enzyme, is required for the synthesis of many neuropeptides. Homozygous deletion of PAM is lethal and mice heterozygous for PAM (PAM+/−) exhibit decreased peptide amidation, increased anxiety‐like behavior, decreased cold‐induced vasoconstriction and increased sensitivity to pentylenetetrazole (PTZ)‐induced seizures. Dietary and genetic limitations to Cu availability result in phenotypes similar to those observed in PAM+/− mice. We tested the hypotheses that increased dietary Cu could ameliorate deficits identified in PAM+/− mice and decreased dietary Cu could cause similar deficits in wildtype (WT) mice. PAM+/− and WT mice were supplemented with Cu (14d; 70 ppm Cu in drinking water), fed a Cu deficient diet (9 wk; Harlan Teklad 80388) or controls. As assessed in the elevated zero maze, anxiety‐like behavior was sensitive to Cu supplementation in PAM+/− mice and to Cu depletion in WT mice. Laser Doppler monitoring of tail blood flow in cold‐exposed mice revealed the ability of Cu supplementation to restore vasoconstriction in PAM+/‐ mice and Cu depletion to impair vasoconstriction in WT mice. Cu deficiency increased seizure sensitivity of WT mice (PTZ; 30 mg/kg ip). Serum levels of PAM activity rose in Cu deficiency and fell following Cu supplementation. Cu availability may affect similar parameters in man.Grant Funding SourceNational Research Service Award from the National Institute of Mental Health
Calpain 2 is activated downstream of wall shear stress and sphingosine‐1‐phosphate to induce endothelial cell sprout formation in three dimensional collagen matrices
Authors: Kang Hojin , Kwak Hyeongil , Kaunas Roland , Bayless Kayla 
Published: June 2021

New blood vessel growth is essential for vascularization of wounded tissues. Endothelial cells are integral for this process and are stimulated by growth factors and platelet‐derived lipids such as sphingosine‐1‐phosphate (S1P), while also integrating mechanical signals, such as wall shear stress (WSS). However the molecular signals activated downstream of these cues are not completely defined. Previously, we have established a system to demonstrate that S1P and WSS combine to stimulate primary endothelial cell invasion of 3D collagen matrices. S1P and WSS induced Akt phosphorylation and MMP‐2 activation that correlated with invasion responses. Here we determined whether calpain regulates S1P and WSS‐induced invasion into 3D collagen matrices. WSS and S1P combined to enhance calpain activation. Pharmacological inhibitors of calpain 2, but not calpain 1, significantly reduced S1P and WSS‐induced endothelial sprout density and thickness. Also, Akt phosphorylation and MMP‐2 activation were attenuated by calpain inhibition. To confirm a functional role for calpain 2, short hairpin RNA was delivered using recombinant lentiviruses. Silencing of calpain 2, but not calpain 1, blocked WSS/S1P‐induced EC invasion. These data support an integral role for calpain 2 in mediating S1P and WSS‐induced invasion responses in 3D collagen matrices.Grant Funding SourceAmerican Heart Association
Late Neointimal Hyperplasia in Vein Grafts Expands via TGF‐β/CTGF Mediated Fibrosis
Authors: Jiang Zhihua , Tao Ming , Omalley Kerri A , Wang Danlu , Ozaki C. Keith , Berceli Scott A 
Published: June 2021

IntroductionIn weeks to months following implantation, neointimal hyperplasia (NIH) in vein grafts (VG) transitions from a cellularized to decellularized phenotype. Inhibition of early cellular proliferation failed to improve long‐term VG patency. We have previously demonstrated that TGF‐β /CTGF pathways mediate a conversion of fibroblasts to myofibroblasts in the early VG (<2wks). We hypothesize that these similar pathways drive fibrosis observed in the late VG lesion.MethodsWithin rabbit VGs, real time RT‐PCR, Western blotting, and immunohistochemistry were used to examine TGF‐β /CTGF pathways in late (1‐6 month) NIH.ResultsAll VGs exhibited a steady NIH growth (p=0.006) with significant reduction in cellularity (p=0.01) over time. Substantial TGF‐β profibrotic activities, as evidenced by enhanced TGF‐β1 activation, TGF‐β types I to II receptor ratio, SMAD2/3 phosphorylation, and CTGF production, persisted throughout the observation period. Increased matrix synthesis was accompanied by a temporal reduction of MMP2 (p=0.001) and 9 (p<0.001) activity.ConclusionVG NIH is characterized by a conversion from a pro‐proliferative to profibrotic morphology. Enhanced signaling via TGF‐β /CTGF coupled with reduced MMP activities promotes progressive fibrotic NIH expansion. Modulation of late TGF‐β /CTGF signaling may offer a novel therapeutic strategy to improve the long‐term VG durability.
Massively‐Parallel Sequencing Of Nascent RNA Sequencing Reveals Widespread Pausing And Divergent Initiation From Mammalian Promoters
Authors: Lis John T , Core Leighton J , Min Irene , Waterfall Joshua J 
Published: June 2021

RNA polymerases are highly‐modulated molecular machines. We have developed a highly‐sensitive method (GRO‐seq) that maps the position, amount, and orientation of transcriptionally‐engaged RNA polymerases across the entire genome, and have applied it to a primary human fibroblast cell line, and to mouse embryonic stem (ES) cells and isogenic embryonic fibroblasts (MEFs). In this method, nuclear run‐on reactions allow RNA polymerase to incorporate BrU affinity‐tags into nascent RNA that is fragmented, purified 10,000 fold, and subjected to large‐scale parallel sequencing. Mapping these sequences to the genome in these different cell types shows that 30% of all genes have promoter‐proximal paused polymerase, that transcription continues kilobases beyond the 3' cleavage for many genes, and that antisense transcription is prevelant. Surprisingly, in addition promoter‐proximal paused polymerase, most promoters also have an engaged polymerase upstream and in an orientation opposite to the annotated gene. This divergent polymerase is associated with active genes, but does not elongate effectively beyond the promoter. These results imply that the interplay between polymerases and regulators over broad promoter regions dictates the orientation and efficiency of productive transcription.This research was supported by NIH.
Tomato Product Adherence Dynamics in African‐American Men at Risk for Prostate Cancer
Authors: Park Eunyoung , Stacewicz‐Sapuntzakis Maria , Sharifi Roohollah , Freeman Vincent , Xie Hui , Tampe Carolyn , Bowen Phyllis E. 
Published: June 2021

African‐American (AA) men have the highest incidence of prostate cancer (PC) and tomato product (TP) intake is associated with reduced risk. Can AA men significantly increase self‐selected TP intake through diet counseling alone? AA men with PSA ≥ 2.5 ng/mL were randomized to either increase TP intake (intervention group (IG), N = 22) through weekly telephone calls, or to a control group (CG, N=14) receiving no TP coaching over 3 months. Mean dietary lycopene intake was 24.6 ± 27.1 and 5.8 ± 9.6 mg/d, respectively for IG and CG (p = 0.04). The IG consumed a mean of 7.1 TP servings/wk and CG only 3.5 (p = 0.005). The IG increased plasma lycopene level by 53% and 40%, at 1 and 3 months (p = 0.001, p = 0.003, respectively), while there was no increase in the CG. Subjects with high baseline leukocyte DNA damage had significantly less damage after 3 months (22.8%). Incentives/impediments to TP intake were assessed weekly in the IG. Incentives in order of frequency were (1) in study, (2) likability, (3) mass media, (4) social support. Impediments were (1) forgot, (2) run out, (3) hospitalization/sick, (4) tight budget. AA men at risk for PC were able and willing to increase TP intake sufficiently to raise plasma lycopene levels and decrease DNA damage over 3 months. Self‐selected whole food interventions through diet counseling alone may be a feasible approach for efficacy studies.Support: Roybal Center Health Promotion, UIC
Finding cancerous anaplastic cells with image analysis
Authors: Nicol Kathleen , Plaskow Mark Edward , Barr Thomas , Billiter Dave 
Published: June 2021

ObjectiveAdvancing cancer research and location with image analysisMethodThe application was built using Microsoft technologies including Visual Basic 6.0, Visual Basic .NET, C++.NET, and SQLServer 2000‐2005. Key points of interest for anaplastic cells are stored in a database during the batching process, allowing for fast retrieval of areas for visual confirmation and analysis.Results87% of all anaplastic nuclei analyzed were located, counted, and highlighted for the using pathologist/reviewer.ConclusionLack of differentiation in cell nuclei is a constant marker for malignancy. With technology, programming, and image analysis breakthroughs such diffusion of nuclei is able to be located for pathologists across cases, studies, slide libraries, etc. using digital pathology. Our team's pixel analysis and experience makes possible the location of nuclei, cytoplasm, and connective tissue areas within digitized slides for measuring, highlighting, counting, etc. Pathologists are able to get electronic decision support in rapidly finding certain features for malignant cancerous tumors.