bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Monocyte Toll‐like receptor Activity In Patients With Metabolic Syndrome
Authors: Kaur Harmeet , Adams-Huet Beverley , Devaraj Sridevi , Jialal Ishwarlal 
Published: June 2021

The Metabolic Syndrome (MetS) is a pro‐inflammatory state and confers an increased risk for both diabetes and cardiovascular disease. There is a sparse data on cellular sources of inflammation in MetS, especially monocytes. Toll‐like receptors (TLRs) TLR2 and TLR4 have been incriminated in atherosclerosis and insulin resistance. The aim of present study was to examine any difference in monocyte activity in terms of expression of TLR2, TLR4 and downstream signaling cascades in MetS patients compared to controls. Surface expression of both TLR2 and TLR4 on monocytes were significantly increased in MetS subjects versus controls after adjustment for waist circumference along with further increase in NFkappa b and p38 MAPKinase activity (p<0.01). Also, priming of monocytes with lipopolysaccharide resulted in significant release of interleukin 1‐beta, 6 and 8 in MetS subjects. TLR4 correlated significantly with IL‐Ib, MCP‐I, NFKappa B and p38‐MAPKinase and TLR2 correlated significantly with IL‐6, NFKappa b and p38‐MAPKinase. Thus this study provides novel data of increased TLR2 and TLR4 activity in MetS serving as a cellular hub for the pro‐inflammatory state.Grant Funding Source : AMERICAN DIABETES ASSOCIATION
Flaxseed lignan supplementation improves markers of obesity in C57BL6 mice
Authors: Ford Nikki A. , Hursting Stephen D. 
Published: June 2021

Overweight breast cancer patients have a poorer prognosis than their lean counterparts which may be attributed to increased inflammation and higher levels of serum hormones. Due to the ineffectiveness of many weight loss regimens we utilized a commercially available flaxseed lignan supplement (Brevail®) to modulate the effects of body fatness on serum and tissue biomarkers. C57BL/6 mice, which are prone to obesity, were fed a 10% fat diet for 8 weeks prior to randomization onto one of two doses of Brevail (0.074 mg (B2) or 0.025 mg (B1) secoisolariresinol diglycoside/ kg diet) for another 8 weeks. Although flaxseed lignan supplementation did not alter final body weight, B2 significantly reduced the percentage of body fat (P=0.017) relative to control fed mice. Hepatic lipid droplets were also reduced in size and number by lignan consumption. Fasting glucose and insulin were reduced in a dose‐dependent manner (P=0.036 and P<0.0001, respectively) while the QUICKI index, which is a measure of insulin resistance, also significantly improved with lignan consumption (P=0.001) relative to control fed mice. B2 also reduced the adipokines resistin and leptin (P=0.001, P=0.032, respectively) which have been implicated in chronic inflammation. Together these data suggest that Brevail supplementation may improve breast cancer risk markers by altering body fatness, obesity‐related adipokines and markers of inflammation.Grant Funding Source: Susan G. Komen
Increased mRNA expressions of atheroprotective proteins in the peripheral blood mononuclear cells of humans taking low‐dose methotrexate
Authors: Chiang En-Pei Isabel , Chih Hui-Min , Chen Der-Yuan , Lan Joung-Liang , Chang Hsin-Yueh , Chen Wei-Wen , Tang Feng-Yao 
Published: June 2021

Methotrexate (MTX) is a commonly prescribed disease‐modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). ATP‐binding cassette transporter‐A1 (ABCA1) and 27‐Hydroxylase (HY27) are known antiatherogenic proteins that promote cellular cholesterol efflux. MTX promotes the reversal of cholesterol transport in vitro. We examined whether clinical MTX use is associated with altered blood lipids and/or ABCA1/HY27 expressions. Plasma lipid profiles and PBMC HY27 and ABCA1 expressions were compared between subjects taking MTX and other DMARDs (MTX‐)(n=100). ABCA1 and HY27 expressions significantly elevated in MTX+ compared to MTX‐subjects. ABCA correlated with MTX doses (r=0.205, p=0.042). MTX+ subjects are more likely to have increased HY27 (OR=2.5, p=0.038). Although no differences were observed in the blood lipids, the potential impacts of MTX on cholesterol metabolism should not be overlooked and the atheroprotective effects from MTX induced HY27 and ABCA1 expressions may still be present in those persons with pre‐existing dyslipidemia.CONCLUSIONSWe demonstrated novel findings on the increased gene expressions of atheroprotective protein HY27 and ABCA1 in human PBMCs with clinical use of low‐dose MTX.
n‐3 PUFAs reorganize B cell membrane rafts and molecular order accompanied by differential effects on B cell function
Authors: Rockett Benjamin Drew , Teague Heather , Harris Mitchel , Shaikh Saame Raza 
Published: June 2021

n‐3 PUFAs manipulate lipid raft organization to suppress T cell and macrophage function; however, little is known about this relationship with B cells, especially at the animal level. We previously established a high n‐3 PUFA dose remodeled mouse B cell raft clustering. To establish relevance, we first tested a n‐3 PUFA dose modeling human intake on B cell raft organization, relative to a control, using biochemical and quantitative imaging methods. Biochemical analysis revealed incorporation of docosahexaenoic acid into phosphatidylcholines of raft‐like domains with no change in cholesterol distribution. TIRF and fluorescence polarization imaging showed n‐3 PUFAs manipulated B cell raft size, increased GM1 expression, and increased membrane order upon cross‐linking GM1 molecules. Finally, we tested the hypothesis that modifying rafts would suppress B cell responses ex vivo. Contrary to expectations, n‐3 PUFAs enhanced LPS‐induced B cell activation, yet suppressed B cell stimulation of naïve CD4+ T cells. Overall, the results demonstrated a relevant n‐3 PUFA dose remodeled rafts; furthermore, the data showed raft remodeling was accompanied by unique changes in B cell function.Grant Funding Source: NIH R15AT006122
Energy Restriction Results in Phenotypic and Functional Alterations to NK Cells
Authors: Clinthorne Jonathan Frederick , Gardner Elizabeth 
Published: June 2021

Energy restriction (ER) is a dietary intervention shown to increase lifespan and reduce the incidence of spontaneous tumors in rodents. Natural killer (NK) cells are innate lymphocytes responsible for tumor surveillance and their activity is altered by ER. We have previously shown NK cell function is reduced in influenza infected ER mice, prompting us to investigate whether ER influences NK cell homeostasis independent of influenza infection. Here, we show 40% ER of young mice results in phenotypic and functional changes to NK cells compared to AL mice. Splenic NK cells from ER mice were analyzed for various cell surface markers associated with NK cell maturation and development using flow cytometry. NK cells from ER mice were not only reduced in number and percentage compared to AL mice; but also expressed significantly less CD11b, CD43, and KLRG1, markers normally associated with mature NK cells. We observed no impairment in the ability of NK cells from ER mice to produce interferon‐γ, but found granzyme B production significantly reduced compared to NK cells from AL mice. Phenotypic and functional changes to NK cells observed in ER mice provide insight into how ER may compromise the innate immune response to intact pathogens. Supported by R01AG034949 (E.G.)Grant Funding Source : NIA
Maternal blueberry diet suppresses Wnt1‐induced mammary tumor progression in offspring
Authors: Rahal Omar , Pabona John Mark P , Hennings Leah , Prior Ronald L , Kelly Thomas , Al-Dwairi Ahmed , Simmen Frank A , Simmen Rosalia CM 
Published: June 2021

Despite the well‐accepted notion of peri‐natal origins of adult diseases, the factors and regulatory mechanisms underlying breast cancer development remain unclear. Diet is a highly modifiable determinant of breast cancer risk, and the effects of the in utero nutritional environment persist beyond fetal life. We investigated whether in utero/lactational exposure to blueberry (BB) via maternal diet alters the trajectory of Wnt1‐induced mammary tumorigenesis in offspring. Wnt1 transgenic mice were exposed to maternal diets of casein (CAS; n=33) or blueberry‐supplemented CAS (3% BB; n=28) from gestation day 4 until post‐natal day 21. Offspring were then weaned to CAS and mammary tumor development was followed until age 8 months. While tumor incidence and latency were similar for both groups, tumor weight (by 2‐fold, p=0.034) and growth rate (by 60%; p=0.008) were reduced in offspring of BB‐ versus CAS‐fed dams. Tumors from the BB group had higher expression of tumor suppressors PTEN and E‐cadherin and lower cyclin D1 and pro‐apoptotic Bcl2 levels. Transcript levels for DNA methylation enzymes DNMT1 and EZH2 were higher in BB tumors. Serum levels of insulin and serum leptin/adiponectin ratio were lower for tumor‐bearing BB than CAS offspring at sac. Our findings support a role for nutritional epigenetics in adult breast cancer outcome.Grant Funding Source : USDA‐CRIS (RCMS), DOD‐BCRP (OR) and NIH‐NCI (FAS).
DNA methylation in candidate genes as a biomarker for transgenerational risk of preeclampsia
Authors: Wright Michelle L. , Anderson Cindy M. , Uthus Eric O. , Ohm Joyce E. 
Published: June 2021

Preeclampsia (PE), characterized by global fetal undernutrition due to placental insufficiency, affects over 100,000 women annually in the US. Gene‐environment interactions resulting from placental insufficiency during critical developmental windows may explain differential methylation of key genes associated with familial risk of PE. In this study, our goal was to validate methylation status of CpG dinucleotides in loci of genes identified via genome‐wide methylation array (Illumina Infinium) in women with and without PE (n=6/group). Differentially methylated loci were primarily located in non‐CpG island regions of genes. Bisulfite sequencing was performed on maternal peripheral blood samples and placental tissue of fetal origin to detect methylated cytosines in 7 candidate genes involved with vascular function, inflammation, and lipid metabolism. Pyrosequencing was performed to identify conversion of unmethylated cytosine to uracil in the altered sequence, providing single‐nucleotide resolution of the segment of DNA. This study provides novel evidence for the generation of epigenomic marks associated with an intrauterine environment of placental insufficiency, providing a putative explanation for the heritable risk of preeclampsia across generations.Grant Funding Source: Robert Wood Johnson Foundation
Targeted messages delivered by nurses and radio improved infant and young child feeding in Mexico
Authors: Monterrosa Eva C , Frongillo Edward A , Gonzalez-Cossio Teresa , Bonvecchio Anabelle , Villanueva Maria Angeles , Thrasher James , Rivera Juan A 
Published: June 2021

Scalable interventions are needed to improve infant and young child feeding (IYCF). We examined effectiveness of a theory‐based communication intervention to improve IYCF in Mexico. Women with children 6–24 mo were selected randomly from vaccination rosters from 6 semi‐urban low‐income communities in Morelos state (intervention, n=266) and 3 in Puebla state (control, n=201). For the intervention, nurses visited participants once at home to deliver 5 messages: breastfeeding, food consistency, flesh‐food and vegetable consumption, and responsive feeding; messages aired 7 times/d for 21 days on 3 radio stations. We used a pre‐post‐test design to evaluate changes in beliefs, attitudes, and intentions via 3‐point scales, and in practices with a 7‐d food frequency. Mixed models were used to examine intervention‐control differences in pre‐post changes. Coverage for the nurse component was 89%, and 34% for radio. Beliefs, attitudes, and intention about IYCF were significantly improved in the intervention communities compared to control. Intervention participants had significantly greater: breastfeeding frequency (2 times/d), vegetable (0.5 day) and beef consumption (0.2 day), and thicker consistency in soups (0.5 day). This study provides evidence that a targeted communication intervention using a scalable model significantly improved IYCF.Funding by Alive & Thrive, Health Services MorelosGrant Funding Source: Alive and Thrive
Feasibility of accelerometers for measuring children's daily physical activity
Authors: Schaefer Sara Elizabeth , Van Loan Marta , Allen Lindsay , German John Bruce 
Published: June 2021

Understanding physical activity is essential in the fight against child obesity. Certain accelerometers may be more useful in assessing this variable in children; easier to wear devices may facilitate better compliance and measurement over longer time periods. The objectives of this study were to a) compare children's acceptability of various accelerometers and b) compare their research utility. Children 7–10 y (n=25) were recruited within Yolo County, CA to test each of three accelerometers; the Philips Actical™ (worn on hip), the SenseWear BodyMedia™ (upper arm) and the Polar Active™ (wrist). Each week children received a device to wear over 5 continuous days. Parents were asked to note device removals. After each use, children and parent each completed a structured interview with trained staff. Upon completion, children were asked to place the devices in order from most to least preferred. The Polar Active was most accepted by children and useful to researchers in providing data on activity intensity levels. This device also engaged children with real time feedback on activity achievements. These findings will aid researchers in choosing measurement tools for children's physical activity.Grant Funding Source : Foods for Health Institute
STIM1 silencing prevents pressure‐overload induced cardiac hypertrophy in mice
Authors: Benard Ludovic Olivier , Jeong Dongtak , Matasic Daniel S , Kohlbrenner Erik , Hajjar Roger J , Hulot Jean-Sebastien 
Published: June 2021

STromal Interaction Molecule 1 (STIM1), a membrane protein of the endoplasmic reticulum (ER), has recently been proposed as a positive regulator of cardiomyocyte growth by promoting calcium (Ca2+) entry through the plasma membrane and the activation of Ca2+‐mediated signaling pathways (Circulation, 2011).To further extend this observation, we studied the impact of STIM1 silencing in pressure‐overload induced mouse model of cardiac hypertrophy using recombinant Associated Adenovirus 9 (AAV9)‐mediated gene silencing. C57/Bl6 Mice were injected with saline (noAAV) or with rAAV9 expressing shRNA against STIM1 (shSTIM1) or a control shRNA (shScr) at 1E+11 viral genome by tail vein injection. Three weeks later, Transverse Aortic Constriction (TAC) surgery was performed (4 experimental groups: sham, TAC‐noAAV, TAC‐shScr and TAC‐shSTIM1). In contrast to TAC‐noAAV or TAC‐shScr, the rAAV9‐shSTIM1 treated animals developed significantly reduced cardiac hypertrophy developed as assessed by echocardiogtaphy and hemodynamics three weeks after surgery. TAC‐ShSTIM1 however displayed left ventricular dilation and a non‐significant trend for depressed systolic function.These results indicate STIM1 as a key regulator of cardiac hypertrophy.
Chinese Visible Human Project and its application
Authors: Zhang Shao-Xiang 
Published: June 2021

“Visible Human Project (VHP)” was initiated by US National Library of Medicine in 1989. Afterwards, the library signed contract with Health Science Center of the University of Colorado to formally carry out the project in August 1991. Accordingly, research team at the University of Colorado collected a structural data set of human body after obtaining successive sectional images. A digital image data set of a complete human male cadaver was acquired and made available for public use in November 1994, which aroused worldwide enthusiasm in this field. And remarkable social and economic benefit has been gained. Thereafter, some countries initiated their visible human project one after another. Korea started 5‐year “Visible Korean Human (VKH)” project (Mar.2000—Feb.2005) in 2000 and first data set was derived from a patient with acquired cerebroma in 2001. China started its project in 1999 which the first data set of Chinese visible human was set up at The Third Military Medical University in October 2002. Before then, by utilizing data made public by US VHP, Chinese scientists in informatics had exerted themselves on preliminary work to pave the way for further achievement. Now VHP research is so promising a scientific field to meet the need of digital era and will be increasingly common in many areas relating with structure and function of human body, the deployment of Chinese Visible Human Project (CVHP) is of great strategic significance in science and technology.Since it was build up nine years ago, CVH data set has been widely applicated in various fields including creating a human body model for radiation protection and for comparing images for B ultra sound diagnosis and making models for surgary simulation.
Estrogen Receptor‐Positive Breast Cancer Cells Drive CAFs to Secrete Leptin and Support Tumor Invasiveness
Authors: Barone Ines , Catalano Stefania , Gelsomino Luca , Panza Salvatore , Marsico Stefania , Giordano Cinzia , Bonofiglio Daniela , Casaburi Ivan , Covington Kyle R , Fuqua Suzanne , Andò Sebastiano 
Published: June 2021

BackgroundTumor phenotype is a result of the complex interactions between malignant cells and surrounding stroma. Leptin, a known cytokine involved in breast cancer development, is expressed by several cells as fibroblasts. K303R estrogen receptor (ERα) mutation, identified in 50% of invasive breast tumors, was associated with worst outcomes.MethodsWild type (WT) and K303R ERα stably transfected MCF‐7 cells for breast cancer. Human Cancer Associated Fibroblasts (CAFs) as stromal cells. Microarray and realtime PCR to evaluate changes in breast cancer‐secreted factors. MTT, Soft Agar and Scratch assays for growth and motility. Leptin release by RIA.ResultsCAFs secrete leptin when cocultured with WT ERα breast cancer cells and to a higher extent in cells expressing the K303R hyperactive ERα. Immunodepletion experiments show that CAFs‐derived leptin, in turn, supports cancer cell invasiveness. Moreover, K303R‐conditioned media (CM) dramatically alter CAFs shape, increase Fibroblast Activation Protein expression, and enhance CAFs viability and motility compared to WT‐CM. We identify Epidermal Growth Factor as a major determinant for K303R‐activated CAFs phenotype.ConclusionsWe uncover a bidirectional cross‐talk between breast cancer cells and ‘educated’ CAFs. Blockade of these intercellular communications represent an effective strategy for molecular targeted therapies in breast cancer.
Transgenic mice overexpressing an endothelial‐targeted Fas‐inducing apoptosis construct exhibit pulmonary hypertension associated with marked lung arterial remodeling
Authors: Goldthorpe Heather , Parsons Sean A. , Jiang Jin-Yi , Deng Yupu , Stewart Duncan J. 
Published: June 2021

ObjectivePulmonary arterial hypertension (PAH) is a lethal disease, characterized by complex vascular lesions and increased pulmonary vascular resistance. To test the hypothesis that lung EC apoptosis at the level of distal pulmonary arterioles is necessary and sufficient to cause PAH phenotype we developed a novel transgenic model.Methods and ResultsThe Fas‐Induced Apoptosis (FIA) construct was expressed under the control of endothelial‐specific, Tie2 promoter in transgenic mice (i.e. EFIA mice). Two transgenic lines characterized by low and high expression levels (LE and HE, respectively) were generated. LE‐EFIA exhibited normal pulmonary hemodynamics and vascular structure at baseline; however, administration of a small molecule dimerizing agent, AP20187, resulted in lung microvascular apotosis and modest dose‐dependent increase in RVSP. Interestingly, HE‐EFIA transgenic mice showed significant elevation in baseline RVSP compared to wild‐type controls even in the absence of the AP compound (34± vs. 24±4 mm Hg, respectively; p<0.005). 40% of HE‐EFIA mice also exhibited perivascular lesions, localized to distal lung arterioles which were highly proliferative by Ki67 and EDU staining, and exhibited variable degrees of apoptosis.ConclusionOur data suggest that EC apoptosis is sufficient to induce PAH, which is associated with marked inflammation and remodeling of lung arterioles.
Profiling candidate housekeeping genes for data normalization in chronic ethanol treated rat liver regeneration model
Authors: Juskeviciute Egle , Vadigepalli Rajanikanth , Hoek Jan B. 
Published: June 2021

This study focuses on selecting suitable housekeeping genes (HKGs) to normalize gene expression data in the regenerating liver of the rats subjected to chronic ethanol treatment. Rats were fed a liquid diet containing 36% of total calories derived from ethanol for 5 weeks; for pair‐fed controls ethanol calories were replaced by carbohydrates. After five weeks, rats were subjected to 70% PHx and liver samples were collected at 1, 6, 12, 24, 36 and 48 h after the surgery.Our global gene expression analysis indicates that almost 50% of hepatic genes are differentially expressed within the first 24 h after PHx. The ideal HKGs should be expressed at a constant level during different stages of liver regeneration and be unaffected by chronic ethanol treatment. We analyzed expression levels of 35 candidate HKGs using a high throughput microfluidic qPCR platform. This set included both traditional HKGs (Actb, Gapdh) and novel candidates selected based on our global gene expression data. Gene expression analysis using modified geNorm algorithm showed that only five of these genes could be considered suitable HKGs in this model. Results of our gene expression data analysis were significantly affected by the choice of HKGs. Our newly characterized HKGs improved the patterns identified for the cell cycle pathway demonstrating the functional validity of our approach.Supported by AA018873, AA008714, AA014986, AA017261.
Developing a completely biological tissue‐engineered blood vessel for clinical use
Authors: L'Heureux Nicolas 
Published: June 2021

In the 1990's, biomaterials were considered an integral part of the new field of tissue engineering, particularly in projects where mechanical functions were important. However, these foreign scaffolds often significantly limited in vivo performance because they interfered with physiological functions (immune, remodeling, mechanical). Our goal was to grow a completely biological human blood vessel in the hope that it could be positively remodeled by the recipient's body.Using normal adult skin fibroblasts, we developed an approach termed Tissue Engineering by Self‐Assembly (TESA) in which sheets of cell‐synthesized extracellular matrix and living cells are assembled into strong complex tissues. Multilamellar tubes where developed as autologous vascular grafts for hemodialysis access. These vessels displayed promising mechanical properties including burst pressures that surpassed those of human arteries. Phase I/II clinical trials have shown promising safety and efficacy results even in a high‐risk patient population. Early clinical results with a second‐generation graft (allogeneic, non‐living) support the feasibility of this more widely available design. A third generation graft, based on cell‐synthesized threads and textile technologies, can be produced three times fasters. This truly biocompatible “biomaterial” can mimic the conjunctive component of many tissues and organs.