bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flavonoid luteolin supplementation inhibits diethylnitrosamine‐initiated alcohol‐promoted hepatic inflammation and precancerous lesions in mice (829.7)
Authors: Rafacho Bruna Paola , Stice Camilla , Liu Chun , Ausman Lynne , Greenberg Andrew , Wang Xiang‐Dong 
Published: June 2021

Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against chronic diseases. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen (diethylnitrosamine [DEN])‐initiated alcohol‐promoted pre‐neoplastic liver lesion mouse model. C57BL/6 mice were injected with DEN (i.p. 25 mg/kg of body weigth [BW]) at 14 days of age. At 8 weeks of age mice were group pair‐fed with Lieber‐DeCarli liquid control diet or alcoholic diet (EtOH diet, 27% total energy from ethanol) and supplemented with a dose of 30 mg luteolin/kg BW/day for a treatment period of 21 days. Results show a significant induction in the incidence and multiplicity of basophilic and eosinophilic foci, markers of pre‐neoplastic liver lesions, in DEN‐injected mice fed EtOH diet. The presence of pre‐neoplastic lesions was significantly correlated with the induction of steatosis and inflammatory foci in these mice. Supplementation with luteolin inhibited the presence of pre‐neoplastic liver lesions in DEN‐injected mice fed EtOH diet. Dietary luteolin significantly reduced the severity of hepatic inflammatory foci with an associated non‐significant reduction in expression of hepatic inflammatory cytokines TNF‐α, IL‐6 and IL‐1β. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1), however, luteolin supplementation significantly reversed alcohol‐reduced SIRT1 activity assessed by the ratio of acetylated and total FoXO1. The study demonstrated that luteolin prevents EtOH diet‐promoted hepatic inflammation and pre‐neoplastic lesion, potentially mediated by SIRT1‐FoxO1 signaling pathway. Grant Funding Source: USDA/ARS grant 1950‐51000‐074S
Skin whitening effects of flower extracts with high antioxidant activities (830.20)
Authors: Lee Bog‐Hieu , Choi Joo‐Yeon , Yu Miri , Jeong Gi Hee 
Published: June 2021

This study was aimed to investigate whitening effect of seven flower extracts with high electron donating ability (EDA). CCK‐8 assay revealed that the cell viability rate of all the flower extracts was significantly higher than that of control. Whitening effects of the flower extracts were measured by mushroom tyrosinase inhibition rate, cellular tyrosinase activity and cellular melanin contents in B16F1 melanoma cells. Rhododendron molle (Blume) G. Don extract reduced mushroom tyrosinase activity by 35.1% than the control and ascorbic acids. At 500 ppm, Aruncus dioicus var. kamtschaticus extract suppressed tyrosinase activity by 45.8%. In case of cellular melanin content, Euscaphis japonica extract was significantly lower than the control and the ascorbic acid. As for gene expression level of TRP‐1, TRP‐2, and tyrosinase, relative quantification value of the Euscaphis japonica extract showed inhibition of expression of three melanogenic enzymes. In conclusion, flower extracts had shown strong whitening effect. These findings suggest that flower extracts may can be further developed and potential skin‐whitening or anti‐melanogenesis preparation for cosmetics and therapeutic use.Grant Funding Source: supported by Basic Science Research Program through the Natiional Research Foundation of Korea(NRF)
Determination of plasma and leukocyte ascorbate concentrations in a randomized, double‐blind trial (830.3)
Authors: Mitmesser Susan , Combs Maile , Evans Mal 
Published: June 2021

Plasma ascorbate reflects recent intake, whereas leukocyte ascorbate more closely reflects cellular stores and total body pool.Objective was to evaluate the bioavailability of ascorbate in plasma and leukocytes from a novel vitamin C formulation.In this double‐blind, cross‐over, males and females between 18‐60 years were randomized to receive one of the following: Placebo (P, 0mg vitamin C), Ascorbic Acid (AA, 1000mg vitamin C) or Ester‐C® (EC, 1000mg vitamin C + threonate and furanone) as a single dosage. Plasma and leukocyte ascorbate were measured at 2, 4, 8, and 24 hours following treatment.An intention‐to‐treat analysis was conducted on thirty six subjects (18 males, 18 females). Plasma ascorbate percent change from Baseline was significantly higher for EC and AA at 2 hours compared to P (EC=135.55±176, AA=126.60±135, P=2.35±33; p<0.001). At 4, 8, and 24 hours the percent change from Baseline was only significantly higher for EC compared to P (all p蠄0.035). The percent change in leukocyte ascorbate was significantly higher from Baseline for EC at 2, 4, 8, and 24 hours (all p蠄0.041) and P at 4 and 24 hours (p蠄0.035) but there was no change from Baseline for the AA group.Vitamin C from Ester‐C and Ascorbic Acid has greater plasma bioavailability than Placebo. Compared to Baseline, Ester‐C® provides a higher percent change in leukocyte ascorbate, which may be due to the presence of threonate and furanone in the formula.
Sasa quelpaertensis leaf extract suppresses inflammation in DSS‐induced colitis in vivo (830.7)
Authors: Kim Kyung Mi , Kim Yoo‐Sun , Lim Ji Ye , Min Soo Jin , Ko Hee‐Chul , Kim Se‐Jae , Kim Yuri 
Published: June 2021

Sasa quelpaertensis Nakai is a species of bamboo grasses grown in Mt.Halla on Jeju Island in South Korea. Sasa leaves have been suggested to have anti‐diabetic, anti‐cancer, and anti‐inflammatory effects. Inflammatory bowel disease (IBD) is a disease characterized by chronic inflammatory disorders of the gastrointestinal tract. The aim of this study is to investigate the possible protective role of Sasa quelpaertensis leaf extract (SQE) on dextran sodium sulphate (DSS)‐induced colitis in mice model. We found that SQE attenuated the severity of IBD assessed by disease activity index (DAI) score, shrinkage of colon length, and histopathological changes. SQE also significantly suppressed the DSS‐induced serum inflammatory cytokines including TNF‐α, IL‐1β and IL‐6. Furthermore, SQE down‐regulates the expression of TNF‐ α, COX‐2, iNOS, NF‐kB, and PPARγ. Furthermore, SQE down‐regulated ERK1/2 phosphorylation, but not p38 or JNK. These results suggest that SQE may a protective role in gut inflammation including IBD via regulation of inflammatory mediators and inflammation‐mediated signal pathway.Grant Funding Source: Support by Rural Development Administration (# PJ009777) & brain korea 21 plus (# 22A20130012143)
Effect of grape consumption on metabolic parameters in obese adults (831.11)
Authors: Giebler Kathryn , Sato Jennifer , Stevens Allison , Ford Sarah , Steinberg Francene 
Published: June 2021

Consumption of polyphenol‐rich grapes has previously shown cardioprotective effects. This randomized, double‐blind, crossover study aimed to determine the impact of whole grapes on biomarkers of cardiovascular disease risk compared to placebo. We examined plasma lipids, glucose, insulin, and C‐reactive protein in obese adults (mean BMI 39.2 ± 11.7) in good health. Diets included 60 g of whole grape powder (WGP), equivalent to 2 cups whole grapes providing 300 mg total polyphenols, or placebo(C) matched in calories and appearance providing 0 mg polyphenols. Subjects completed two 4‐wk intervention periods, separated by a 2‐wk washout, during which they consumed WGP or C once daily in addition to low polyphenol diets. Fasting blood samples were drawn at beginning and end of each intervention period. Acute postprandial effects at 1, 3, and 5 h were examined following consumption of WGP or C with a standardized high fat, high carbohydrate test meal. Preliminary data reveals subjects receiving WGP had no significant differences in fasting metabolic parameters compared to C, with exception of HDL (p<0.05). Similarly, postprandial AUC for glucose, insulin, and TG did not differ. Further evaluation is needed to determine if grape consumption improves other metabolic biomarkers in the obese population.Grant Funding Source: Supported by CTGC and USDA CRIS CA‐S*‐NTR‐6316‐H
Polyphenols from açaí: a strategy to modulate inflammation and hypertension (831.2)
Authors: Daleprane Julio , Aguiar Cristiane , da Silva Renata Cristina , Rainho Rafaela , Moura Roberto , Resende Angela de Castro Resende 
Published: June 2021

The aim of this study was evaluated the anti‐inflammatory effects in vivo model of renovascular hypertension (RH) and in endothelial cells (ECs). Rats were treated with ASE 200 mg.kg‐1.day (or vehicle) for 40 days. Oxidative damage, antioxidant activity and the expression of endothelial nitric oxide synthase (eNOS), superoxide dismutase 1 and 2 (SOD 1 and 2), metalloproteinase (MMP‐2) and tissue inhibitor of metalloproteinases (TIMP)‐1 were determined. Structural changes in the aortic and mesenteric MMP‐2 levels were evaluated. In in vitro experiments, ECs were treated with 100 ug/mL of ASE and the expressions of inflammatory markers were evaluated. ASE reduced the increased mesentery levels of malondialdehyde and carbonyl protein in hypertensive rats. SOD, catalase and glutathione peroxidase activities and SOD1 and 2, eNOS and TIMP‐1 expressions were reduced. ASE prevented the vascular remodeling, as well as, the increased MMP‐2 expression and levels found in hypertensive rats. In ECs ASE was able to decreased TNFα, eNOS and IL‐8 mRNA expression. These results suggest that ASE prevents the endothelial dysfunction and vascular structural changes associated with hypertensionGrant Funding Source: FAPERJ, CNPq and CAPES
Effect of orally administered EPA and DHA on congestive heart failure in rat (831.7)
Authors: Yamanushi Tomoko , Kabuto Hideaki , Hirakawa Eiichiro , Janjua Najma , Takayama Fusako , Mankura Mitsumasa 
Published: June 2021

This study assessed the effect of EPA and DHA on congestive heart failure (CHF) in rat. Four‐week‐old male rats were divided into 4 groups: C (normal, administered saline, n=4‐5); H (with CHF, administered saline, n=10‐11); HE (with CHF, administered EPA‐ethyl ester (EPA‐Et), n=9‐10); and HD (with CHF, administered DHA‐ethyl ester (DHA‐Et), n=10). CHF was produced by subcutaneous injection of monocrotaline (MCT) into 5‐week‐old rats. Starting from 3 days before MCT injection, rats were orally administered (1g/kg body weight) saline or one of the two fatty acids daily, anaesthetized on day 24, their electrocardiograms (ECGs) recorded, serum samples drawn, and then killed. The heart was removed, and kept at ‐80ºC or fixed with paraformaldehyde. Fatty acid levels in the heart and triglycerides in serum were determined. Pathological assessment was performed on heart tissue. The Q and T waves (QT) interval on ECG was significantly shorter (P 蠄 0.05) in C and HD groups than in H and HE groups. In the heart, EPA level was higher in HE group and DHA level higher in C and HD groups, compared to H group (P 蠄 0.05). Triglyceride level was significantly decreased (P 蠄 0.05) in H, HE and HD groups compared to C group. In HD group, mononuclear cells tended to infiltrate less into myocytes than in H group (P = 0.06). The right ventricle weighed significantly more (P 蠄 0.05) in H, HE and HD groups compared to C group. The mean survival rate in the three experiments was 100% for C group, 74% for H group, 65% for HE group and 70% for HD group. Administration of EPA‐Et or DHA‐Et may affect cardiac function through alteration of heart fatty acid composition. Furthermore, DHA‐Et administration may contribute to ameliorating CHF.Grant Funding Source: Supported by JSPS KAKENHI Grant Number 21500788
Effect of immune modulators on the activity of enzymes after experimental myocardial infarction (832.10)
Authors: Sarapultsev Alexey , Gette Irina , Abidov Musa , Sarapultsev Petr , Chupakhin Oleg , Danilova Irina 
Published: June 2021

It was revealed (patent RUS 2437165 from 13.04.2010) that application of immune modulators fosters reducing the severity of inflammation reaction, faster cicatrization, provokes angiogenesis. As tissue regeneration depends on energy supply of the cell, the goal of the research was studying the effect of immune modulators on the activity of enzymes involved in energy exchange in the damaged myocardium. The experiment was conducted with 65 male rats of the Wistar line. The immune modulators used were derivatives of 1,3,4‐thiadiazine (L‐17) and 3‐aminophtalhydrazine (AMP), exerting antioxidant effect as well. Modeling myocardial infarction was verified by morphological research methods and increasing activity of organo‐specific myocardium enzymes in the blood plasma. With experimental myocardial infarction, the myocardium tissue showed CPK activation and decreasing activity of LDH1,2 isoenzymes. Introduction of AMP facilitated faster cardiac enzymes normalization in the blood plasma of the animals than introduction of L‐17. Nevertheless, both compounds prevented decreasing activity of LDH1,2 induced by myocardial infarction modeling in the myocardium at early stages (1 day), without decreasing CPK activity at all stages of the experiment.Grant Funding Source: Supported by grant 12‐Ц‐41059
Targeted inhibition of ATP‐binding cassette transporter A1 protein degradation promotes reverse cholesterol transport and reduces atherosclerosis in mice (832.15)
Authors: Huang Linzhang , Zhu Haibo 
Published: June 2021

Objective ATP‐Bing Cassette Transporter A1 (ABCA1) is a key protein in the rate‐limiting step of reverse cholesterol transport, which maintains plasma HDL levels. Transcriptional regulating ABCA1 promotes HDL generation and RCT is well established, however, little is known about the posttranspcriptional inhibition of ABCA1 degradation on macrophage RCT and atherosclerosis. We therefore investigate whether suppressing ABCA1 degradation would promote RCT and reduce atherosclerosis.Methods and results Pulse‐chase analysis revealed that a small molecular (IMM‐H007) significantly inhibits ABCA1 degradation and facilitates its cell‐surface localization in THP‐1 macrophages. In vitro tests described that IMM‐H007 promote cholesterol efflux via ABCA1‐mediated pathway. Animals fed a western diet containing 1.25% cholesterol with IMM‐H007 treatment showed an increase in circulating HDL levels and enhanced RCT to the plasma, liver, and feces. Additional, elevated hepatic ABCA1 expression and functional HDL were also observed in mice after IMM‐H007 administration. Furthermore, suppressing ABCA1 degradation gave rise to the reduction of plaque size, lipid content and increase markers of plaque stability in apoE‐/‐ mice.Conclusion Our findings reveal that raising HDL levels by inhibiting ABCA1 protein degradation enhances reverse cholesterol transport and decreases plaque formation, suggesting that it is a promising HDL therapeutic strategy to protect against atherosclerotic. IMM‐H007 could be a leading compound for development of drugs for raising HDL quantity and function.
Elderly individuals with high IL‐6 levels have proinflammatory HDL (832.16)
Authors: Farazmand Marya , Dadgostar Amir , Seddigh Farhad , Reuben David 
Published: June 2021

Introduction: High density lipoprotein removes the oxidatively modified lipids and other toxic molecules from peripheral cells for elimination and thus it is anti inflammatory and protective. Under chronic acute phase pressure, unsaturated fatty acids and phospholipids in HDL undergo oxidative modification and that results in HDL losing its anti inflammatory and protective capacity. Objective: we sought to determine if HDL from individuals with inflammatory background can retain its protective ability. Methods: We recruited a group of elderly, visiting the UCLA clinics (n=40), who had normal (Group 1) or higher than normal plasma IL‐6 levels (Group 2). We followed the UCLA Medical Center IRB rules and instructions and analyzed their plasma sample for HDL anti inflammatory capacity. This was done using monocyte chemotactic activity toward human artery wall cells in co culture. Results: While the plasma HDL cholesterol levels of the two groups was similar (59.2+ 7.6 and 61+6.9 mg per dL respectively) with no significant difference, the HDL protective capacity of the group with high serum IL‐6 level was significantly lower than the group 1 who did not have high circulating IL‐6 levels (‐ 35% vs + 67% respectively, p <0.01). Conclusion: The data obtained indicates that in the elderly with high plasma IL‐6 levels the inflammatory pressure results in the loss of the protective capacity of HDL and this in turn moves the organism toward a vicious cycle. HDL protects lipids and other substances form oxidative modification. Los of HDL protective capacity increases the modification of lipids and other macromolecules in LDL, in cell membrane and basically throughout the organism with the pursuing undesirable structural and functional consequences.Grant Funding Source: NIH
The role of endothelial nitric oxide synthase coupling status during acute hyperglycemia as determined by real‐time measurements of blood nitric oxide and hydrogen peroxide in rat (832.2)
Authors: Bertolet Matthew , Minni Michael , Galbreath Tyler , Patel Shan , Selko Robert , Barsotti Robert , Young Lindon , Chen Qian 
Published: June 2021

Acute hyperglycemia impairs vascular dilatory function in normal subjects. Normally, vascular endothelial function depends on nitric oxide (NO) production from coupled eNOS in the presence of cofactor 5,6,7,8‐tetrahydrobiopterin (BH4). By contrast, 7,8‐dihydrobiopterin (BH2, oxidized form of BH4) and/or lack of L‐arginine (eNOS substrate) causes eNOS uncoupling to produce superoxide (SO), which can be quickly converted to hydrogen peroxide (H2O2). The role of eNOS coupling status in mediating acute hyperglycemia‐induced vascular dysfunction is not known. We simultaneously measured blood NO and H2O2 during the infusion of saline (control), or 20% glucose with or without BH4 (MW=314 g/mol, 6.5 mg/kg), or L‐arginine (MW=211 g/mol, 600 mg/kg), or BH2 (MW=239 g/mol, 4 mg/kg) by NO or H2O2 microsensors (100 µm, WPI Inc.) from the femoral veins of male Sprague‐Dawley rats. We found that acute hyperglycemia (200 mg/dL, n=6) significantly increased blood H2O2 and reduced blood NO levels compared to the saline group over a 3 hr. period (n=7, p<0.05). By contrast, BH4 (n=6), or L‐arginine (n=5‐6), not BH2 (n=6‐7), significantly reduced blood H2O2 and improved vascular NO levels (p<0.05). This study provides novel evidence indicating that eNOS uncoupling during acute hyperglycemia causes endothelial dysfunction and oxidative stress. Promotion of eNOS coupling may be beneficial to maintain normal vascular function.Grant Funding Source: Supported by Center for Chronic Disorders of Aging and Department of Bio‐Medical Sciences at PCOM
Alteration of retinal vascular development by postnatal systemic lipopolysaccharide administration: a novel model of retinopathy of prematurity (832.6)
Authors: Hong Hye kyoung , Oh Joo youn , Park Ji Hyun , Park Ji Yeon , Park Kyu Hyung , Choi Chang Wong , Woo Se Joon 
Published: June 2021

Purpose: ROP is the leading cause of blindness in the children. Inflammation is being highlighted as the major factor for the morbidity of prematurity. We intended to investigate the effect of neonatal systemic inflammation on the retinal angiogenesis in newborn rats and to show the role of inflammation in the retinopathy of prematurity.Method: Systemic inflammation was induced by the pre‐ and post‐natal intraperitoneal injections of lipopolysaccharide (LPS) in neonatal rats. Enucleation and retinal separation was performed at 1 and 2 post‐natal weeks. Analyses on morphology of retinal vessels, recruited immune cells, change of inflammatory cytokines were assessed with immunofluorescence, FACS and RT‐PCR.Result: Administration of LPS postnatlly, not prenatally, induced inflammation in the retina with recruitment of CD11c positive cells and increased expression of a set of inflammatory cytokine genes. Postnatal LPS administration also suppressed retinal vessel development and deranged the retinal vascular structures combined with abnormal vascular tuft formation that resembles features of retinopathy of prematurity.Conclusion: Neonatal systemic inflammation alters the normal development of retinal vessels by inducing retinal inflammation. Our model of systemic inflammation‐induced abnormal development of retinal vasculature can be a novel experimental model of retinopathy of prematurity.
Comparison of cynomolgus macques (Macaca fasicularis) basic coagulation paprameters based on genetic origin versus attributed sources (833.4)
Authors: Waller Donald , McGeehan Elizabeth , Dubach Jean , Sinacore James 
Published: June 2021

Cynomolgus macaques (Macaca fascicularis) are increasingly being used for a wide variety of studies, including anticoagulant therapy development and toxicology testing. Cynomoglus macaques are sourced from several different countries, some have indigenous populations and some have established breeding colonies from unknown indigenous populations. Genetic monitoring can verify the source of the macaques but is not usually included in study group monitoring. Small study group numbers and heterogeneous groups of animals can create difficulty in statistical interpretation of study results. The present study compares coagulation responses from animals attributed to sources in Vietnam, Cambodia, Philippines, Indonesia, China and Mauritius. Genetic characterization of 12 microsatellite loci used a Beckman/Coulter capillary electrophoresis system to determine genotypes. The baseline clotting profile was evaluated by determination of prothrombin time (PT), activated partial thromboplastin time (aPTT), common pathway (Heptest®), and thrombin time (TT). Blood was drawn and stored in EDTA for genetic analysis or immediately transferred to sodium citrate tubes, centrifuged to obtain plasma and stored at ‐80oC. Clotting tests were performed using the ACL 300+ and BBL Fibro System manual fibrometers. Statistical analysis for heterogeneity were performed with the groups of animals by their attributed source and reanalyzed after regrouping by genetic data. The heterogeneity was highly significant when the groups were evaluated based only on their attributed source, but was not significant when assigned to groups based on genetic characterization. The animals sourced from Mauritius were consistently more homogenous when compared to the other sources.A clear understanding of the genetic background can insure group consistency and is essential when applying specific statistical tests to interpret data.