bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Bohr‐Haldane Effect on Hb‐O2 Binding to Electrical Regeneration in CHD
Authors: Delgado-Almeida Antonio Rafael 
Published: June 2021

AIMDespite extensive clinical and basic research, the precise mechanism for Hb‐O2 binding remains to be determined. Since we have confirmed that ↑RBC K rapidly reverses angina, ST‐T alterations, and induces electrical regeneration of heart in CHD, we tested the hypothesis that RBC K transport is involved on Hb‐O2 binding in human RBC.Methods/SubjectsHeparin venous sample from healthy subjects were analyzed before (4 ml) and after in Vitro oxygenation (4 ml +1ml 100% O2). In all pH, PO2/PCO2, HCO3 (Stat Profile pHOx), RBC/plasma electrolytes (Na, K, Atomic Emission Spectrophotometry), Cl (Lytek‐Cl). Statistical using Student's t‐test, analysis of variance, p<0.05 as exponential values.ResultsIn Vitro blood oxygenation (O2 Sat 87±3 vs 47±6%) resulted in sharply ↓ RBC Ki (87.6± 2.3 vs 92.0±2.3 mmol/lcell, p<4.5E‐09), ↓ RBC Nai (5.8±0.2 vs 6.3±0.2 mmol/lcell, p<6.5E‐05) along with ↓ plasma K (3.3 ±0.3 vs 3.8±0.2 mmol/l, p<9.7E‐05), ↓ Na (134±4 vs 139±2.2, p<1.3E‐03) and ↓ Cl (91±1.6 vs 98.3±1.2 mmol/l, p<7.9E‐11), uncovering a complex biochemical event in Hb‐O2 binding and Bohr Effect, which excludes a simple gas diffusion.ConclusionThis observation strongly support our novel therapeutic approach improving RBC K, and probably myocardial O2 transport in CHD. Second, it is proposed that RBC K exchange should be included in evaluation of Bohr‐Haldane Effects in clinical and experimental human Hb‐O2 exchanges.
Endothelial cell responses to laminar flow: changes in gene expression, protein, and glycocalyx
Authors: Meledeo Michael Adam , Bynum James A , Sondeen Jill L , Bowman Phillip D 
Published: June 2021

Previous studies have shown that endothelial cells (ECs) respond to laminar flow and behave more like ECs in vivo. The purpose of this study was to determine the effects of laminar flow on endothelial cells from large compared to small vessels with gene expression analysis, western blotting, and confocal microscopy. Human umbilical vein endothelial cells and dermal microvascular endothelial were grown in Ibidi μ‐VI chamber slides and exposed to 10 or 0.1 dynes/cm2 or static conditions for 24 h. RNA from replicate chambers were isolated, labeled and hybridized to Agilent human whole genome microarrays. Western blots from the same samples were prepared and probed for Syndican‐2, CD31, CD44, CD31 and heparan sulfate. Fixed specimens were prepared for confocal microscopy. Microarray analysis showed that several hundred genes were either up‐ or down‐regulated when ECs were subjected to laminar flow of 10 dynes/cm2 compared to static or low flow. These included gene networks associated with cell morphology, cellular movement, angiogenesis, and inflammation. Changes in cell morphology and rearrangement of glycocalyx elements were observed following flow treatment in both ECs.Funding provided by USAMRMC.
Functional consequences of ROS‐induced ROS release in vascular endothelium
Authors: Roos Carolyn M. , Zhang Bin , Miller Jordan D. 
Published: June 2021

We have previously shown that global reductions in mitochondrial antioxidant capacity and induction of reactive oxygen species (ROS)‐induced ROS‐release (RI‐RR) do not impair endothelial function in young mice due to compensatory increases in an apparent NAD(P)H oxidase‐derived endothelium‐derived hyperpolarizing factor (EDHF). In the present study, we hypothesized that endothelial MnSOD is a major determinant of the functional consequences of RI‐RR, and NAD(P)H oxidase‐derived H2O2 is the major compensatory EDHF released from endothelium when MnSOD is reduced. MnSOD was reduced in endothelium by crossing MnSODFL/FL mice with mice carrying cre‐recombinase driven by a Tie‐2 promoter (Cre+). Aorta from Cre+/MnSOD+/+ and Cre+/MnSODFL/+mice were used for studies of endothelial function. Maximum relaxation to acetylcholine (MR, ACH) was not affected between Cre+/ /MnSOD+/+ and Cre+/MnSODFL/+ mice (61%±1.9, 61%±2.6; respectively). Incubation with apocynin did not change MR, ACH in Cre+ /MnSOD+/+ mice (63%±2.0), but significantly impaired MR, ACH in Cre+/MnSODFL/+ (42%±4.7). Incubation with catalase did not effect MR, ACH in Cre+/MnSOD+/+ mice, but substantially impaired MR, ACH in Cre+/MnSODFL/+ mice (61%±1.2, 48%±1.7). We conclude that inducing RI‐RR in endothelium by reducing MnSOD elicits a compensatory increase in EDHF production, most likely from an increase in NOX2‐derived H2O2.NHLBI
The Effect of Treadmill Exercise on the Regulation of Protein Synthesis during IL‐6 Induced Cancer Cachexia
Authors: Puppa Melissa , White James , Sato Shu , Carson James 
Published: June 2021

Cachexia is associated with the loss of skeletal muscle mass and a reduction in myofibrillar protein synthesis related to the suppression of the IGF‐1/mTOR signaling pathway. The purpose of this study was to determine if treadmill exercise training could offset IL‐6 over‐expression induced suppression of IGF‐1/mTOR signaling pathway. ApcMin/+ mice, an IL‐6 dependent model of colon caner cachexia, were trained on a treadmill 6d/wk 1h/d at 18m/min starting at 6wk of age. Between 12–14wks of age mice were electroporated with either an IL‐6 overexpression (IL6+) or control (CON) vector. Muscle IGF‐1 mRNA was reduced 50% by IL6+, while exercise increased muscle IGF‐1 mRNA 1.3 fold regardless of IL‐6 overexpression. Phosphorylation of mTOR(S2448), p70(T389), and 4EBP‐1(S65) were decreased 50% by IL6+. Exercise was able to attenuate the decrease in mTOR, p‐70, and 4EBP‐1 phosphorylation independent of changes in p‐AKT. These data show that treadmill exercise training can prevent IL‐6 induced skeletal muscle loss by attenuating the suppression of IGF‐1/mTOR signaling in skeletal muscle.Funded by RO1CA121249‐01
Cranberry bioactives augment the activation status of THP‐1 monocytes/macrophages
Authors: Creasy Rebecca A , Khoo Christina , Percival Susan S 
Published: June 2021

Cranberries contain proanthocyanidins (PAC), which have been suggested to interact with immune cell pathogen recognition receptors. We hypothesized that recognition of cranberry PAC would alter cellular function toward an activated state. THP‐1 monocytes were incubated with cranberry fractions and analyzed by flow cytometry with FITC‐CD49a. Cranberry fractions activated monocytes in a time and dose dependent manner as shown by increased expression of CD49a on the surface. Cytokines and chemokines secreted in the culture medium were analyzed by multiplex technology. MIP‐1a, MIP‐1β, and IL‐8 were secreted by the cells without marked secretion of pro‐inflammatory cytokines, IL‐1a, IL‐1β, TNF‐a, and IL‐6. Significantly more MIP‐1a mRNA was present. This suggests compounds found in cranberry can activate monocytes to help regulate immune cell trafficking. A second experiment was designed to determine if cranberry primes immune cells. THP‐1cells were differentiated into macrophages and treated with cranberry fractions or DMSO vehicle for 16 hr. Cells were then washed and challenged with LPS for 6 hr. A trend toward increased MIP‐1a protein was found in cranberry‐treated cells compared to vehicle‐treated cells. Taken together, this suggests that cranberry bioactives prime THP‐1 macrophages for a heightened response upon pathogen challenge.Grant Funding Source : Ocean Spray Cranberries, Inc. and AES, University of Florida
Co‐culture supernatants of toxigenic Clostridium difficile 43285 with specific Lactobacillus and Bifidobacterium species significantly attenuated IL8 and MIP3α induction and restored epithelial viability
Authors: VijayaKumar DeepakKumar , Nanthakumar Nanda 
Published: June 2021

Interleukin‐8 (IL8) and macrophage inflammatory protein 3α (MIP3α) are chemokines secreted by the intestinal epithelium to attract innate immune cells during the onset of inflammatory responses. During C. difficile infection in human, these chemokines are significantly induced to attract the neutrophils to the site of infection. In this study, we investigated the impact of culturing specific probiotic (Lactobacillus or Bifidobacterium species) and commensal (B. fragilis) bacterium with virulent C. difficile 43285 and assayed for IL8 and MIP3α responses in CaCo‐2 cells. CaCo‐2 cell is a model for human enterocytes. Only the co‐culture of C. difficile with L. paracasei, L. casei, L. plantarum, L. rhamnosus LGG, L. delbruikii, B. infantis and B. adolescentis significantly attenuated IL8 and MIP3α responses compared to the monoculture supernatant of C. difficile. This suggests specificity of few probiotics and may suggest that coculture with these probiotics may act to neutralize the toxins and other virulence factors of C. difficile or create a metabolic environment that makes it less favorable for C. difficile to become virulent. Cell viability assay showed that CaCo‐2 cells treated with these specific probiotic co‐cultured supernatants showed enhanced viability as compared to the supernatant of C. difficile. This suggests that the culture supernatants of specific probiotic co‐cultures may possess metabolites that are likely to prevent inflammatory response and ultimately cell death in human enterocytes.Supported by NIH grant RO1HD059126; Contact: Dr. Nanda Nanthakumar; e‐mail: nanthaku@helix.mgh.harvard.edu
CCN1 induces death of esophageal adenocarcinoma: Trick or TRAIL?
Authors: Chai Jianyuan , Norng Manith , Pham Jennifer , Wu Sing-Yung , Jamal M Mazen 
Published: June 2021

BackgroundSelectively to kill cancer cells has always been a dream of all oncologists. TRAIL has shown promising effect in several types of cancer. A recent study demonstrated a synergistic apoptotic effect of TRAIL and CCN1 in prostate cancer. This study is to investigate the role of CCN1 in esophageal adenocarcinoma (EAC).MethodsExpression of CCN1 and TRAIL were assessed in EAC cells (OE33) and the tumor tissue by quantitative PCR. Normal esophageal cells (Het‐1A) and tissue were used as control.Results(1) CCN1 expression was down by 65% (P < 0.01, N = 15) in OE33 cells compared in Het‐1A cells; and by 95% (P < 0.05, N = 3 normal and 12 EAC) in EAC tumors compared in normal esophageal tissue. (2) OE33 cells expressed TRAIL receptors but not TRAIL ligand, while Het‐1A cells just the opposite. (3) CCN1 up‐regulated pro‐apoptotic genes (e.g. TRADD 181 fold) in OE33 cells, but promoted anti‐apoptotic genes (e.g. BIRC5 137 fold) in Het‐1A cells. (4) TRAIL induced apoptosis in OE33 cells but not in Het‐1A cells. TRAIL and CCN1 combination increased apoptosis by 35% (P < 0.01, N = 3) in OE33 cells. (5) Mixed culture of OE33 and Het‐1A cells caused massive death of OE33 cells.ConclusionsTRAIL can selectively kill EAC cells without harming normal esophageal cells due to the lack of receptor, and CCN1 can enhance the effect. Expression of TRAIL receptors but not the ligand is a strategy of EAC to escape potential cell death. The study was supported by the VA Merit Review.
Effects of whole and refined grains on cardiometabolic risk factors in a controlled‐feeding, weight loss study: Preliminary findings
Authors: Harris Kristina Arline , West Shiela , Heuvel Jack Vanden , Jonnalagadda Satya , Kris-Etherton Penny 
Published: June 2021

Making “half your grains whole” is recommended to reduce risk of chronic disease; yet, evidence from clinical trials is mixed. Our aim was to study the effects of chronic whole (WG) and refined grain (RG) intake on cardiometabolic risk factors in a controlled‐feeding setting. Overweight or obese (BMI 25–42 kg/m2) men (n=25) and women (n=25) aged 35–55 with increased waist circumference and at least 1 other Metabolic Syndrome criterion were randomized to a healthy diet containing either WG or RG. An isocaloric diet was provided for 6 weeks followed by a hypocaloric diet (~500 kcal/day) for 6 weeks. Both groups had reductions (p for time <0.001) in body weight, waist circumference, abdominal % body fat, C‐reactive protein, insulin, triglycerides, HDL‐C, LDL‐C, and blood pressure, but group differences for these endpoints were not significant. Fasting plasma glucose (FPG) tended to decrease more with WG compared to RG (−1.2±0.9 vs −4.0±0.9 mg/dL, p=0.1) while controlling for baseline FBG and weight loss. In a subgroup analysis, there was a greater decrease in the number of prediabetic participants (FPG ≥100 mg/dL) from baseline to study end in the WG (10 to 1) compared to the RG group (8 to 7). In conclusion, a healthy diet led to significant improvement of cardiometabolic risk factors in an “unhealthy overweight” population while WG provided extra benefits for glycemic control, particularly in prediabetic individuals.Grant Funding Source : Bell Institute for Health and Nutrition, General Mills, Inc.; NIH Grant M01RR10732; ClinicalTrials.gov NCT00924521
Problem solving strategies and the relationship between visualization ability and spatial anatomy task performance
Authors: Nguyen Ngan , Mulla Ali , Nelson Andrew J , Wilson Timothy D 
Published: June 2021

BackgroundIn a previous study, we showed that visualization ability (VZ) is related to performance on a spatial anatomy task (SAT). Low VZ learners demonstrated consistently poorer task performance than high VZ learners. In the current study, we explored the processing commonalities and differences of learners in order to determine which problem solving strategies distinguish those of high VZ from those of low VZ.MethodsForty‐two students completed a standardize measure of VZ, the SAT, and a questionnaire involving self‐analysis of the processes and strategies used while performing the SAT.ResultsConsistent with our previous study, high VZ learners performed better on the SAT than low VZ learners. Concerning problem solving strategies, more low VZ learners reported using movements of body parts and/or surrounding objects while performing the SAT. These learners also stated they were more concerned about time, that is finishing all SAT questions, than they were about answering correctly.ConclusionThe tendency for low VZ learners to offload cognitive work onto external perceptual‐motor processes suggests that they have problems with mental manipulations, which may contribute to their poor SAT performance. Furthermore, low VZ learners are more prone to errors while performing the SAT, as suggested by their tendency to focus on the quantity, rather than the quality, of their answers.Grant Funding Source: none
Assessment of whole body cholesterol pool size in Smith‐Lemli‐ Opitz syndrome children using liquid chromatography tandem mass spectrometry
Authors: Myrie Semone B , Merkens Louise , Yang Haifeng , Roullet Jean- Baptiste , Steiner Robert D , Jones Peter J 
Published: June 2021

Smith‐Lemli‐Opitz syndrome (SLOS) patients typically exhibit abnormally low cholesterol, high 7‐dehyrocholesterol (DHC) and 8‐DHC levels in tissues and plasma. Therapeutic intervention for SLOS is aimed at maximizing whole body cholesterol pool size (WBCP) while down‐regulating biosynthesis to decrease the buildup of potentially toxic precursors. The study aim was to develop a sensitive liquid chromatography‐tandem mass spectrometry (LC/MS/MS) method for detection of changes in blood isotope cholesterol enrichment over time, for assessment of WBCP in SLOS patients receiving supplemental dietary cholesterol. Subjects (n=13; mean age: 7±1 yr) were given iv [18O]cholesterol (1.0–1.4 mg/kg bodyweight) or D7‐cholesterol (0.9–1.4 mg/kg). Blood samples were collected at baseline and over a 10 wk period, cholesterol extracted from RBC, derivatized with piconyl ester and analyzed using LC/MS/MS. The [M+H] +>[M‐picolinic acid] + transition was chosen for monitoring, with 18O‐cholesterol at m/z 494>369 and D7‐cholesterol at 499>376. WBCP was 427.3 ±52.0 mg/kg bodyweight. Plasma cholesterol level was not related to WBCP (p>0.05), but inversely related to 7DHC and 8DHC (p<0.05). In summary, LC/MS/MS is a sensitive method for stable isotopic assessment of WBCP in humans. This study is the first assessment of WBCP in children and in SLOS patients. The data will be a useful reference for a longitudinal SLOS study.Grant Funding Source : NIH
ABCG5/G8 deficiency results in reduced intestinal cholesterol and fatty acid transport
Authors: Zhang Linda Shuo , Kohan Alison B , Tso Patrick 
Published: June 2021

Adenosine triphosphate‐binding cassette (ABC) half transporters G5 and G8 are critical in protecting the body from the accumulation of dietary phytosterols, which is associated with an elevated risk of coronary heart disease. Expressed in the liver and intestines, they are proposed to promote phytosterol excretion and to limit phytosterol absorption. However, the role of G5/G8 in cholesterol and fatty acid (FA) absorption is unclear. The aim of this study was to investigate the effects of G5/G8 deficiency on intestinal lipid transport in chow‐fed mice. We employed the conscious lymph fistula model to examine radiolabeled dietary cholesterol and FA transport into the lymph using wild‐type (WT) and G5/G8 knockout (KO) mice. Since it has been thought that G5/G8 promote sterol excretion, we were surprised to find that G5/G8 KO mice displayed a ~53% reduction in dietary cholesterol transport into the lymph compared to WT controls. In addition, G5/G8 KO mice also displayed a ~45% reduction in FA transport into the lymph. This reduction in cholesterol and FA transport was also accompanied by an accumulation of cholesterol and FAs in the intestinal lumen, suggesting that the loss of G5/G8 inhibit transport across the enterocyte. We conclude that G5/G8 deficiency results in reduced intestinal cholesterol and FA absorption in mice, and therefore may play a previously unknown role in intestinal lipid absorption.Grant Funding Source: University of Cincinnati
Feeding Blueberry Diets Dose‐Dependently Inhibits Bone Resorption in Young Rats
Authors: Zhang Jian , Lazarenko Oxana P. , Badger Thomas M. , Ronis Martin J. , Chen Jin-Ran 
Published: June 2021

Nutritional status is a critical factor that influences bone development. We previously reported that weanling rats fed AIN‐93G semi‐purified diets supplemented with 10% whole blueberry (BB) powder for only two weeks beginning on postnatal day 21 (PND21) significantly promoted bone formation. However, whether there is an effect of BB diet on bone at lower levels of supplementation or if there are additional effects on bone resorption is unknown. The current study examined the effects of three levels of BB diet supplementation (1, 3, and 5%) for 14 days beginning on PND21on osteoclastic bone resorption. Using peripheral quantitative CT scan of tibia, we demonstrated that bone mineral density and content were dose‐dependently increased in BB rats compared to control AIN‐93G fed animals (p < 0.05). Proteins were isolated from long bone of femurs, and Western blot revealed that RANKL (the cytokine receptor activator of nuclear factor‐κB ligand essential for osteoclast formation) protein expression was dose‐dependently decreased (p<0.05). This was accompanied by decreased expression of PPARγ, RANKL and TRAP (Tartrate‐resistant acid phosphatase) mRNA expression (p<0.05). These results indicate significant stimulation of bone growth by dose‐dependent inhibition of bone resorption after BB consumption during early development. Supported in part by ARS CRIS #6251‐51000‐005‐03S.Grant Funding Source: USDA / ARS CRIS
Pediatric Overweight Prevention through a Parent Training Program for 2–4 year old Latino Children
Authors: Slusser Wendelin , Neumann Charlotte , Cumberland William , Renenger Kristel , Fischer Heidi , Frankel Fred 
Published: June 2021

The objective of this study was to measure over a one‐year period, whether a parent training based on social learning theory combined with evidenced based interventions to promote optimal nutrition and physical activity will reduce the upward trend of BMI z‐scores in groups of 2–4 year old Latino children living in low‐income households.MethodsA randomized controlled pilot study evaluated the effectiveness of the intervention contrasting 61 children whose mothers were randomized to receive Parent Training (PT) with 60 Wait‐list (WL) subjects. 7 weekly classes with 2 booster classes were delivered to mothers. Forty subjects did not attend the one‐year follow up assessment resulting in 81 subjects who have measurements for both baseline, and one‐year follow up assessments. To adjust for differential dropout rates and missing observations, imputation of missing data was done using a carefully constructed model.ResultsThere were no significant subject differences between groups at baseline for family characteristics and BMI categories for child and mother. Children in the intervention group decreased their z scores significantly on average by .20 (SE= .08) compared to children in the control group who increased z scores on average by .04 (SE=.09) at one year (P<.05).ConclusionPT is effective to reduce the risk of overweight in preschool Latino children living in low‐income households.
Estrone‐3‐Sulfate is a substrate to verify functionality of uptake transporters in primary hepatocytes
Authors: Keiser Markus , Radebold Jennifer , Ullrich Anett , Damm Georg , Nüssler Andreas , Siegmund Werner , Runge Dieter 
Published: June 2021

BackgroundPrimary mammalian hepatocytes are used for several in vitro applications like testing of drug metabolism, toxicity and transporter assays. However, little is known about species specific differences or similarities in the activity of uptake and efflux transporter. Therefore, we started a species specific characterization and comparison of uptake transporters functionalities in relevant species used for drug testing. Here, we report the uptake of estrone‐3‐sulfate (E3S) in primary hepatocyte cultures of human, rat and monkey.MethodsHepatocytes were incubated in serum free media. Two ‐ four days after cell isolation a time and concentration dependent uptake of [3H]‐E3S was measured using liquid scintillation counting. Rifampicin was added in various concentrations to measure its effects on E3S uptake.ResultsAll hepatocytes showed at 37 °C a time‐dependent and saturable increase in E3S uptake compared to the uptake at 4 °C. E3S revealed a high affinity to human (Km = 12.9 ± 10.1 μmol/l; Vmax = 84.2 ± 30.3 pmol/mg × min) and monkey (Km = 8.2 ± 2.3 μmol/l; Vmax = 31.3 ± 3.6 pmol/mg × min) but not to rat hepatocytes. Rifampicin clearly inhibited the E3S uptake in monkey hepatocytes while rat hepatocytes were not influenced.ConclusionOur data suggest that [3H]‐E3S is a suitable substrate to verify the functionality of uptake transporters in primary hepatocytes of humanoids but not of rats.