bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of nuts on coronary heart disease and cancer risk in type 2 diabetes (825.8)
Authors: Nishi Stephanie , Kendall Cyril , Bashyam Balachandran , Augustin Livia , Jenkins David 
Published: June 2021

Background: Diabetes increases the risk of coronary heart disease (CHD) by 2‐4 fold, and the risk of the majority of cancers by 1.2‐2‐fold, where CHD and cancer are two of the leading causes of morbidity and mortality worldwide. Dietary factors have long been implicated in both cancer and CHD, where diet and lifestyle changes are said to reduce risk by 10‐80%. Nuts are one dietary factor that have been associated with reduced CHD and cancer risk in epidemiological studies.Objective: To determine the effect of nut consumption on cancer cell proliferation and its association with oxidative damage.Methods: A 12 week randomized controlled trial was completed by 100 participants with type 2 diabetes consuming one of 3 isocaloric supplemental diets; 1) full‐dose nut diet (~75 g mixed nuts per day), 2) half‐dose nut diet, or 3) control diet, incorporated into a background NCEP Step 2 diet. In vitro prostate cancer cell (LNCaP) proliferation, used as a marker of cancer risk, and markers of oxidative damage for CHD risk were analyzed using available fasting blood obtained at weeks 0 and 12.Results: No treatment differences were observed. However, across treatments, when data were pooled, nut consumption was associated with increased protein thiols (P=0.001) and decreased LNCaP proliferation (P=0.01). Conjugated dienes were positively correlated with LNCaP proliferation (R=0.22, P=0.03).Conclusion: Nut consumption has been associated with reduced CHD risk, though more studies may be required to elucidate the mechanism for CHD reduction, as well as the effect on cancer risk.Grant Funding Source: Supported by the Canadian Foundation for Dietetic Research (CFDR)
Choline deficiency decreases proliferation of embryonic neural progenitor cells through inhibiting epidermal growth factor pathway (827.2)
Authors: Wang Yanyan , Mehedint Mihai , Corbin Karen , Friday Walter , Zeisel Steven 
Published: June 2021

Choline deficiency can alter the development of fetal hippocampus. Epidermal growth factor (EGF) is pivotal for neural progenitor cell (NPC) proliferation in the embryonic ventricular and subventricular zones. To address the possibility that EGF signaling pathway plays a functional role in the effect of choline deficiency, we cultured NPCs derived from E14 mouse hippocampus and treated them with low choline (5 µM) or medium choline (70 µM). Low choline significantly suppressed the phosphorylation of EGF receptor (EGFR) and activation of downstream effectors ERK1/2 and Akt after stimulation of NPCs with EGF. Moreover, low choline decreased the EGFR protein expression and half‐life in NPCs. There were no changes observed on the EGFR mRNA expression and degradation of EGFR protein. However, low choline remarkably inhibited the EGFR nascent protein synthesis. Our findings reveal that choline deficiency influences NPC proliferation by suppressing EGFR signaling pathway, which might have long‐term effects in the brain.Grant Funding Source: North Carolina Biotechnology Center (NCBC)
In vivo therapeutic modulation of stress response signaling by Pitanga (Eugenia uniflora) extracts in C. elegans for neuroprotection (829.24)
Authors: de Medeiros Katia , Stavinoha Rebecca , Correia Roberta , Vattem Dhiraj 
Published: June 2021

The effect of red (RP) and purple (PP) Pitanga (Eugenia uniflora) L. spray dried and freeze dried powders on modulating stress response signaling was evaluated in transgenic C. elegans carrying promoter‐GFP constructs for several genes in the IGFR/PI3K/AKT, ARE/NRF2, Sir2.1/AMPK, mTOR/HIF‐1α, apoptosis/cell cycle and UPR signaling pathways. Relative fold changes in gene expression in response to pitanga treatments were quantified flurometrically. Neuroprotective effects of RP and PP in experimentally induced neurodegeneration were evealuated in C. elegans models for Alzheimer’s disease (AD) and Parkinson’s disease (PD). For AD, time to thermally induced Aβ1‐42 aggregation mediated paralysis was evaluated in transgenic C. elegans (CL4176). For PD, MPP+ induced neurodegeneration was qualtified by loss in motility due to paralysis. Results suggest an upregulation in ARE and Sir2.1 signaling in response to Pitanga treatment. Treatment with polar acidic, polar basic and polar neutral fractions, abrogated Aβ1‐42 induced paralysis and MPP+ induced neurodegeneration for PD by 15‐22%. The processing technology used to produce Pitanga powders significantly impacted bioactivity.Grant Funding Source: Supported by: Vrdür Foundation (USA) & CAPES (Brazil)
Dietary intake of antioxidant nutrients and peripheral plasma determination of T‐BARS in normal weight and obese Mexican people (830.14)
Authors: Hernandez‐Guerrero Cesar , Garcia‐Del Rio Sandra , Romo‐Palafox Ines , Hernandez‐Chavez Paulina , Zelonka‐Montes de Oca Rosa , Perez‐Lizaur Ana 
Published: June 2021

The study objective was to evaluate the consumption of antioxidants and the oxidative stress condition in the peripheral compartment of Mexican obese people. The control group (CG) included 52 participants with a BMI of 18.5‐24.9. The overweight (OW) group included 31 participants with BMI of 25‐29.9 and the obesity group (OB) included 64 participants with IMC>30. A standardized antioxidant food frequency survey was applied to assess the intake of antioxidant vitamins A, C, E and the minerals: Cu, Mn, Se and Zn. T‐BARS concentration was assayed in plasma spectrophotometrically. The intake of vitamins, minerals and the T‐BARS concentration were compared with ANOVA of Kruskal‐Wallis between groups; a p<0.05 was accepted as a statistical difference. There were not differences between the consumption of minerals and vitamins between the CG, OW and OB groups. The concentration of T‐BARS in CG, OW and OB were 5.5+/‐3.8 µM, 6.1+/‐5.2 µM and 15.9+/‐8.2 (p<0.05 versus CG), respectively. When OB group was stratified by obesity degrees the concentration of T‐BARS were 14.9+/‐8.9, 15.2+/‐6.7 and 14.8+/‐8.1 for OB‐1 (BMI 30‐34.9), OB‐2 (BMI 35‐39.9) and OB‐3 (BMI>40), respectively. There were no statically differences between stratified OB groups and all of them showed difference (p<0.05) versus CG. The consumption of vitamins and minerals by CG, OW and OB groups showed similar values; however the oxidative stress marker (T‐BARS) in peripheral plasma of OB group showed a robust increase in comparison with CG and OW groups, respectively.Grant Funding Source: Supported by Universidad Iberoamericana Ciudad de Mexico
Konjac glucomannan and inulin modulated the immune function in a murine model of dextran sodium sulfate‐induced colitis (830.2)
Authors: Han Yi‐Chun , Chen Hsiao‐Ling Chen 
Published: June 2021

This study was to investigate the protective effects of konjac glucomannan (KGM) and inulin on colonic colitis in a dextran sodium sulfate (DSS)‐induced murine model.During the 21‐d diet period, six‐week‐old C57BL/6J mice were randomly assigned and fed AIN‐93 diet (vehicle, DSS group) or fiber‐supplemented (KGM 2%, Inulin 2%, or KGM 1% + Inulin 1% w/w) diet. In the following 5‐d DSS period, all mice were fed AIN‐93 fiber‐free diet while drinking water with DSS (3% w/v) was offered only to DSS and fiber groups. Mice were sacrificed on the 3rd of DSS‐withdrawn period. The colonic tissues were collected to determine the pathohistology and gene expression of tight junction proteins by RT‐PCR. The plasma TNF‐α and IL‐10 were also analyzed.DSS group had the greatest weight loss and DAI throughout the DSS period and its index of colitis continued to increase in the DSS‐withdrawn period. At the end of the study, the crypt depth was reduced at the proximal colon and severe colitis occurred at the distal colon in the DSS group, which was ameliorated with fiber supplementation. In addition to that, soluble fiber normalized the DSS‐induced alteration in the plasma TNF‐α and IL‐10 levels and the gene expression of occludin.Pre‐supplementation of KGM and inulin prevented the colitis‐related symptoms in the DSS‐induced colitis.
Purple Perilla frutescens extracts enhanced cholesterol efflux and inhibited ER stress in macrophages exposed to oxidized LDL (831.8)
Authors: Park Sin‐Hye , Kang Young‐Hee 
Published: June 2021

There is growing evidence that excess lipids can stimulate endoplasmic reticulum (ER) stress in atherosclerosis. However, the pathophysiological importance and the underlying mechanisms of this phenomenon remain unknown. The current study tested that oxidized LDL promoted ER stress in macrophages, which was blocked by purple Perilla frutescens extracts (PPE). The ER stressor tunicamycin was employed as a positive control. Treating oxidized LDL for 24 h accumulated lipid droplets in macrophages and formed foam cells, evidenced by Oil red O staining. PPE suppressed foam cell formation, but enhanced ATP‐binding cassette (ABC) transporter A1 and G1, cholesterol efflux markers. Oxidized LDL as well as tunicamycin induced the ER stress markers of activating transcription factor 6 and this effect was blocked by 蠅5 μg/ml PPE, indicating that intracellular toxic lipids in macrophages initiated ER stress. PPE also down‐regulated the induction of the ER resident chaperone BiP/Grp78. The LXR ligand TO‐0131917 increased ABCA1 expression that was blunted by the ER stressor. Accordingly, an upstream mechanism that links toxic lipids to ER stress may entail the action of lipid chaperones through inhibition of LXR. Purple Perilla frutescens extract (PPE) is an annual herb of mint family, which has possessed against inflammation and cancer. Therefore, PPE enhanced cholesterol efflux and inhibited ER stress in macrophages exposed to lipotoxic signals associated with atherosclerosis.Grant Funding Source: Supported by Ministry for Food, Agriculture, Forestry and Fisheries and Brain Korea 21 plus
Transmigration of M1 and M 2 macrophages in pulmonary vessels following intratracheal bleomycin (834.7)
Authors: Wang Ping , Martin William 
Published: June 2021

We have demonstrated macrophage transmigration in pulmonary vessels in murine lungs following bleomycin (Am J Pathol. 2011 Jun; 178(6):2560‐72). Because there are two distinct phenotypes in macrophages, M1 and M2, we wanted to compare the difference between them in transmigration of pulmonary vessels. To address this, we intratracheally instilled bleomycin (3.33 U/kg) into female adult mice (C57BL/6J, n=8). Lungs were isolated at day 2‐21 after bleomycin and cryostat sectioned for immunostaining with iNOS and arginase I to identify M1 and M2 macrophages, respectively. We used ki67 as the marker of cell proliferation. We used confocal microscopy to image pulmonary vascular region covered from the lumen to the perivascular interstitium. We found that more macrophages expressed arginase I [6.7‐fold to iNOS, p<0.05, unpaired t‐test], indicating that more M2 than M1 macrophages transmigrated in pulmonary vessels after bleomycin. Also, up to 20% M2 macrophages revealed ki67 expression (2‐fold to M1 macrophages, p<0.05) in arteriolar region, indicating higher local proliferation of M2 macrophages there. Our results provide direct evidence that primarily M2 macrophages transmigrated in pulmonary vessels. In addition, M2 exhibited more proliferation than M1 macrophages in pulmonary arterioles after bleomycin. This suggests an important role of M2 macrophages in bleomycin‐induced inflammation. (Funder: NIH)Grant Funding Source: NIH
The bronchial hyperactivity in children with pollinosis (834.9)
Authors: Saparova L. , Rozenson R.I. , Abduldayeva A. 
Published: June 2021

Aim of the study was to develop an easy available technique of lung function monitoring in pollinosis patients to predict the clinical course of disease both in seasonal exacerbation period and during the winter remission. Material: We studied 98 children with pollinosis aged 6‐14 years. Peak flow (PF) parameters were studied 3 times per day, namely in the morning, lunch time and in the evening, from the first of April to 30th October. Patients’ history records included hay fever symptoms and peak flow data. The curves of PF were drawn for disease monitoring and prediction. Results: Analyzing the daily changes of peak expiratory flow parameters, we estimated that in children with hay fever sensibilization to Artemisia species without evident asthma symptoms already at the second season peak expiratory flow decreased by 15‐20% and during the third season decreased further by 30% from the best parameters of the first year.Most striking in our studies was the finding that after the pollination season especially in children with disease duration more than 3 years and who did not receive the specific immunotherapy the level of changes decreased, but the type of PF curve didn’t change. In prognosis the most important was the possibility of pollen asthma appeared in most children already during the second hay fever season and was easy predictable by “bad” peak expiratory flow curves ‐ second and third type.
The role of the locus coeruleus in the coping response to social stress (839.1)
Authors: Melson Michael , Wood Christopher , Lombard Calliandra , Wood Susan 
Published: June 2021

Psychosocial stress is linked to psychiatric disorders such as depression. Using a social stressor in rats (resident‐intruder model) we previously identified two phenotypic responses to social stress. One population (45%) exhibited a passive coping response and assumed a defeat posture within a short latency (SL, <300s). The other phenotype (55%) exhibited proactive coping behaviors and a longer defeat latency (LL, >300s). Furthermore, SL rats developed endocrine and behavioral characteristics resembling depression, while the LL phenotype remains resilient. As the locus coeruleus (LC) is a stress‐sensitive brain region that is implicated in the stress coping response, it may mediate individual differences in the response to social stress and resulting pathology. Therefore the present study utilized the neurotoxin DSP‐4 to selectively lesion the noradrenergic LC prior to social stress. DSP‐4 treated rats exhibited decreased active coping behaviors upon the first exposure to social stress (upright posture: veh; 124±40, DSP‐4; 56±42). Furthermore, 5 days after the 5th exposure to social stress, DSP‐4 rats exhibited a reduction in sucrose intake compare with controls (Con: 84%, Veh: 80%, DSP‐4, 72%). These data suggest that lesioning the LC shifted rats towards a passive coping response and increase anhedonic behaviors. Therefore, the LC may mediate a protective effect over consequences of social stress.Grant Funding Source: Supported by NARSAD 17830 and 13BGIA 14370026
Social learning reverses conditioned aversion to nicotine via oxytocin receptor in the infralimbic cortex in rats (839.4)
Authors: Han Wenyan , Chen Hao 
Published: June 2021

The initial aversive response to cigarettes in most smokers is thought to be ameliorated by the presence of peers who also smoke. We previously reported that social learning (i.e. detecting an odor cue associated with nicotine from peer rats) reversed the development of conditioned taste aversion (CTA) between self‐administered nicotine and a contingent olfactogustatory cue in adolescent rats (PMID:21796102). Herein, we focused on the role of oxytocin in infralimbic cortex (IL) as a mechanism for the effect of social learning. Bilateral lesions of IL before (F1,13=18.1, p=0.001) but not after (F1,16=0.481, p>0.05) self‐administration reduced the effect of social learning on tests of CTA. We also found that carbon disulfide contained in rats’ breath was the signal mediating social learning and its effect also required intact IL. We then infused a specific oxytocin receptor antagonist, desGly‐NH2‐d(CH2)5[D‐Tyr]OVT, (0.028 ~ 2.8 μg/ml, a gift from Dr. Mannings) bilaterally into the IL, which dose‐dependently reduced the effect of carbon disulfide on nicotine CTA (F4,30=3.9, p=0.01). The highest dose of the antagonist had no effect on i.v. saline control rats. These results suggested that the release of oxytocin in the IL is a critical signal that reversed the conditioned aversion between nicotine and its olfactogustatory cue, which in turn enabled voluntary nicotine intake in adolescent rats.Key words: nicotine; aversion; social learning; infralimbic cortex; oxytocin
The role of adenosine in helper T cell differentiation and function (840.1)
Authors: Klann Jane , Drygiannakis Ioannis , Gomez Bobbie , Thai Rosarlin , Ernst Peter 
Published: June 2021

Background and Aims: Extracellular signaling molecules, such as anti‐inflammatory adenosine, play a major role in restraining immune response and protecting tissue from inflammatory damage. Adenosine is generated from the ATP through the action of ectonucleoside triphosphate diphosphohydrolase 1 (CD39) that sequentially dephosphorylates ATP to ADP to 5’‐AMP, which is then catabolized to adenosine by ecto‐5'‐nucleotidase (CD73, Nt5e). The aim of this study was to investigate the role of extracellular adenosine in control of helper T cell (Th) cell differentiation and cellular function. Results: Adenosine levels were controlled with a pharmacological approach using the non‐hydrolysable adenosine analog, NECA. Naïve CD4+ T cells were differentiated in vitro in the presence or absence of NECA in selective culture conditions. The presence of NECA suppressed the production of IL‐17a in cells isolated from Th17 conditions. We then explored a genetic approach to control adenosine levels in vivo, using an adoptive transfer colitis model. According to the model, the transfer of CD4+CD45RBhi cells, a subset that contains largely T effector (Teff) cells, will induce colitis when transferred to Rag1‐/‐ mice. Colitis can be ameliorated with the co‐transfer of CD4+CD45RBlo, a cell population with a primarily regulatory phenotype. T cells were isolated from Nt5e‐/‐ mice to investigate the function of Th cells compromised in the ability to produce adenosine. In our adoptive transfer studies, CD73 on both Treg and T effector proved to be necessary for Treg to prevent Teff‐induced colitis. Conclusions: Adenosine signaling has the ability to restrain Th17 response during differentiation through the direct reduction of the production of the pro‐inflammatory cytokine IL‐17a. The ability to produce adenosine is essential for effective Treg activity and compromising the adenosine pool changes the differentiation patterns of Th cells causing excessive inflammatory activation and tissue damage.Grant Funding Source: Supported By: T32 Gastrointestinal Training Grant
Anti‐angiogenic anti‐tumor activity of BJ‐1301, an α‐tocopherol analog (842.5)
Authors: Banskota Suhrid , Chandra Regmi Sushil , Gautam Jaya , Ku Jin‐Mo , Nam Tae‐gyu , Jeong Byeong‐Seon , Kim Jung‐Ae 
Published: June 2021

Because reactive oxygen species (ROS) are generated upon activation of growth factor receptors including VEGFR, and direct application of ROS induces angiogenesis, many natural and synthetic antioxidants including vitamin E were examined and found to have a certain level of antiangiogenic activity. In the present study, we observed that a synthetic aminopyridinol antioxidant, BJ‐1301, inhibits vascular endothelial growth factor (VEGF)‐induced angiogenesis in the growing chick embryo chorioallantoic membrane (CAM), and tumor growth on CAM xenografted with A549 human lung cancer cells. The inhibitory effects of BJ‐1301 were more potent than those of natural and synthetic counterparts, α‐tocopherol (α‐TOH) and 2,2,5,7,8‐pentamethyl‐6‐hydroxychroman (PMC), as well as SU4312, a VEGF receptor tyrosine kinase inhibitor. BJ‐1301 also inhibited ROS generation by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), a direct activator of NADPH oxidase with greater potency than α‐TOH and PMC, and a similar potency trend was observed for their antiangiogenic activities in vivo as well as in vitro (BJ‐1301 > PMC > α‐TOH). Together, these results suggest that BJ‐1301, the aminopyridinol analog of α‐TOH, induces stronger inhibition of both angiogenesis and tumor growth than α‐TOH, PMC, or SU4312 by targeting NADPH oxidase.Grant Funding Source: This work was supported by the Basic Science Research Program through the National Research Foundati
Regulation of hypoxia inducible factors by Sprouty2 (842.9)
Authors: Hicks Kristin , Patel Tarun 
Published: June 2021

Sprouty2 (Spry2) is an inhibitor of receptor tyrosine kinase signaling. Spry2 levels are decreased in cancers of the breast, lung, prostate and liver, thereby permitting excessive receptor tyrosine kinase signaling in these pathologies. Furthermore, a decrease in Spry2 levels has been correlated with poor patient prognosis. In development and tumor growth, cells experience a hypoxic environment to which they adapt to by up regulating the transcription factors, Hypoxia Inducible Factors (HIFs). The HIFs are composed of a beta subunit (HIF1β or aryl hydrocarbon nuclear translocator (ARNT)) and an oxygen sensitive alpha subunit (HIF1α or HIF2α). Using a hepatocellular carcinoma cell line (HuH7), we have shown that Spry2 decreases the protein levels of HIF1α, HIF2α, and ARNT without altering the mRNA levels. Additionally, Spry2 reduces the ability of the HIFs to induce transcription as measured by luciferase assays and mRNA levels of their target genes. We also show that Spry2 interacts with HIF1α and ARNT and that Spry2 decreases the stability of ARNT and HIF1α. To begin to deduce the mechanism, we have shown that Spry2 enhances the ubiquitination of HIF1α. Collectively, our data reveal a novel regulation of the HIFs by Spry2.Grant Funding Source: Supported in part by NIH grant GM 073181
Coincident intracellular calcium rise is essential for Gi/o‐mediated activation of TRPC4 (843.3)
Authors: Thakur Dhananjay , Zhu Michael 
Published: June 2021

TRPC4 is a member of the Canonical Transient Receptor Potential family of non‐selective cation channels. Na+ and Ca2+ influx through the active TRPC4 channel elicits membrane depolarization and intracellular Ca2+ signaling in various cell types including neurons, vascular endothelium and smooth muscle cells. It has been well‐established that homomeric TRPC4 channels are synergistically activated by co‐stimulation of two separate G protein pathways, Gq/11 and Gi/o. However, it remains unclear which step(s) or constituent(s) of the Gq/11 pathway is(are) essential for synergizing with Gi/o proteins to maximally activate TRPC4 channels. Using patch‐clamp recordings and fluorescence membrane potential measurements in HEK293 cells heterologously coexpressing mouse TRPC4β and Gi/o‐coupled µ opioid receptor, we have identified intracellular Ca2+ rise as the primary event associated with Gq/11 activation that synergizes with Gi/o stimulation to elicit maximal TRPC4 current. We also show that a signification portion of this effect is independent of calmodulin although Ca2+‐calmodulin can enhance channel activation. Our experiments demonstrate the contribution of phosphoinositide hydrolysis and IP3 receptors but rule them out as essential players. These findings argue for a critical role of intracellular Ca2+ rise in TRPC4 activation by Gi/o‐coupled receptors and illustrate the key requirements that support TRPC4 as a coincidence sensor of multiple signaling pathways.Grant Funding Source: American Heart Association