bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Age, Sex, Body Mass Index and APOE Genotype on Cardiovascular Biomarker Response to an n‐3 Polyunsaturated Fatty Acid Supplementation
Authors: Thifault Elisabeth , Cormier Hubert , Bouchard‐Mercier Annie , Rudkowska Iwona , Lemieux Simone , Couture Patrick , Vohl Marie‐Claude 
Published: June 2021

ObjectivesTo test whether age, sex, body mass index (BMI) and the apolipoprotein E (APOE) genotype are associated with the metabolic response to an n‐3 PUFA supplementation.Methods210 subjects followed a 2‐wk run‐in period based on Canada's Food Guide, and underwent a 6‐wk 5g/d fish oil supplementation (1.9g of EPA + 1.1g of DHA). Biochemical markers such as plasma lipids, inflammatory markers, and glycemic parameters were measured.ResultsN‐3 PUFA supplementation was associated with a decrease of plasma triglyceride (TG) levels (p 0.0002) as well as with an increase of fasting glucose (FG) levels (p = 0.02). Age was associated with post‐intervention plasma total cholesterol (total‐C) (p = 0.01), low‐density‐lipoprotein cholesterol (LDL‐C) (p = 0.007), apolipoprotein B (Apo‐B) (p = 0.04) and insulin (p = 0.002) levels. Sex was associated with post‐intervention plasma high‐density‐lipoprotein cholesterol (HDL‐C) levels (p = 0.02). BMI was associated with plasma FG (p = 0.02) and insulin levels (p <0.0001) after the supplementation. APOE genotype was associated with FG (p = 0.001) and C‐reactive protein (CRP) levels (p = 0.03) after the supplementation.ConclusionResults suggest that age, sex, BMI, and the APOE genotype contribute to the inter‐individual variability observed in the metabolic response to an n‐3 PUFA supplementation. Funding: CIHR MOP‐229488
A targeted lipidomic analysis of renal oxylipins in kidney disease reveals differences in the effects of dietary flax compared to fish oil
Authors: Devassy Jessay Gopuran , Yamaguchi Tamio , Ibrahim Naser , Ravandi Amir , Aukema Harold M 
Published: June 2021

Oxylipins are fatty acid metabolites (e.g. eicosanoids from arachidonic acid, AA) generated by cyclooxygenase (COX), lipoxygenase (LO) and cytochrome P450 (cP450) pathways. Since oxylipins have differing biologic effects, a targeted lipidomic analysis of oxylipins was performed using kidneys from normal and PCK rats with renal disease, in which disease was affected by dietary soy, flax and fish oil. Of 76 oxylipins scanned by LC/MS/MS, 59 were quantified. Heat map analyses showed that α‐linolenic acid (ALA) oxylipins were higher only with flax oil feeding, while linoleic acid oxylipins were lower to a similar extent with flax and fish oil compared to soy oil. Docosahexaenoic acid (DHA) oxylipins were higher only with fish oil, but both fish and flax oil resulted in higher eicosapentaenoic acid (EPA) oxylipins, although the effect of fish oil was greater. While AA oxylipins were generally lower with both flax and fish oil compared to soy oil, the effect was greater for fish oil for COX and cP450 products, but similar for LO products. The differential effects of flax compared to fish oil on oxylipins may help explain their differential effects in health and disease.Grant Funding Source:CIHR 230564
Effect of Magnolia/Phellodendron on Cortisol and Mood State in Moderately Stressed Subjects
Authors: Talbott Shawn , Talbott Julie , Pugh Michael 
Published: June 2021

Magnolia (Magnolia officinalis) and Phellodendron (Phellodendron amurense) barks are medicinal plants commonly used as traditional remedies for reducing stress and anxiety. Modern supplements are intended to induce relaxation and reduce stress and stress‐related eating. Previous studies have shown the combination of Magnolia/Phellodendron (MP) to reduce both cortisol exposure and the perception of stress/anxiety, while improving weight loss in subjects with stress‐related eating.We assessed salivary cortisol exposure and psychological mood state in 56 subjects (35 men and 21 women) screened for moderate stress and supplemented with a standardized/patented MP combination (ReloraTM, Next Pharmaceuticals) or Placebo for 4 weeks.Salivary cortisol exposure was significantly (p<0.05) reduced by −18% in the Relora group. Significant (p<0.05) mood state improvements were found in the Relora group for Overall Stress (−11%), Global Mood State (+11%), Vigor (+18%), Anger (−34%), Fatigue (−31%), and Confusion (−27%). These results indicate that daily supplementation with a combination of Magnolia and Phellodendron (Relora) reduces cortisol exposure and perceived stress, while improving a variety of mood state parameters, suggesting an effective natural approach to the detrimental health effects of chronic stress.This study was funded by Next Pharmaceuticals and conducted by SupplementWatch
Fortifying whole wheat flour with folic acid does not change the prevalence of folate inadequacy nor the percentage of Canadians with intakes above the Tolerable Upper Intake Level (UL)
Authors: Chan Yen‐Ming , MacFarlane Amanda , O'Connor Deborah L 
Published: June 2021

While folic acid fortification of white wheat flour in Canada has reduced neural tube defects, whole wheat flour does not fall under the current mandate. Our aim was to estimate the impact of adding folic acid to whole wheat flour on the folate intake distribution of Canadians. Twenty‐four hour dietary recalls and supplement intake data collected in the 2004 Canadian Community Health Survey 2.2 (n=35,107) were used for the analysis. The amount of folic acid added to whole wheat flour‐containing foods was set to be equivalent to the amount of folic acid in comparable white wheat flour products. SIDE (Software for Intake Distribution Estimation) was used to model distributions of folate intake and to estimate the prevalence of folate inadequacy (POFI) using the Estimated Average Requirement (EAR) cut‐point method and the proportion of the population with folic acid intakes >; UL. After folic acid addition to whole wheat foods, the POFI and intakes above the UL did not change among non‐supplement users (95% CIs overlap). Likewise, the POFI and percentages of intakes above the UL did not change after whole wheat flour fortification in supplement users (95% CIs overlap). Mean folate intake increased (432±3 to 454±3 μg DFE, p<0.0001) when whole wheat foods were fortified. In conclusion, adding folic acid to whole wheat flour will not likely change the POFI or proportion of folic acid intakes >; UL among Canadians. YC funded by NSERC‐CGS.Grant Funding Source: NSERC
Effect of vitamin‐D on ROS, ICAM‐1 and monocyte adhesion in human umbilical vein endothelial cells (HUVECs) treated with high glucose and acetoacetate
Authors: Kanikarla‐Marie Preeti , Jain Sushil K. 
Published: June 2021

Monocyte adhesion to the endothelium plays a central role in the progression of endothelial dysfunction and cardiovascular disease (CVD). Epidemiological studies report a relationship between vitamin‐D (VD) deficiency and increased risk of CVD in diabetic patients. This study examines whether or not VD supplementation is beneficial in preventing endothelial dysfunction in diabetes. HUVECs were treated with 1, 25‐(OH)2‐D3 (0–50nM) for 24h, and later exposed to the ketone body acetoacetate (AA; 0, 2, 4, 8mM) or high glucose (HG, 25mM) for 24h. There was an increase in ROS, ICAM‐1 expression, and monocyte adhesion in HUVECs treated with AA or HG. VD (50nM) supplementation lowered ROS (41%, p<0.05), ICAM‐1 (73%, p=0.05) and p‐NFêB (50%, p<0.05) expression, and IL‐8 (16%, p=0.05) and MCP‐1 (41.2%, p<0.001) secretion in HUVECs treated with AA. VD significantly inhibited (37.5%, p=0.05) monocyte adhesion to HUVECs exposed to AA. VD had a similar beneficial effect on HUVECs treated with HG. Apocyanin (NADPH oxidase inhibitor), reduced ROS in HG or AA treated HUVECs. The role of VD in inhibiting NADPH oxidases and ROS is under investigation. This study provides the biochemical mechanism through which VD supplementation can lower ROS, ICAM‐1 expression, monocyte adhesion to the endothelium, and thereby the risk of CVD in diabetes.Grant Funding Source: NIDDK and Office of Dietary Supplements
L. reuteri NCIMB 30242: The Sunshine Probiotic ?
Authors: Jones Mitchell L. , Martoni Christopher J. , Prakash Satya 
Published: June 2021

Background/ObjectivesLow serum 25‐hydroxyvitamin D (25(OH)D) is a risk factor for cardiovascular disease (CVD). Bile salt hydrolase (BSH) – active Lactobacillus reuteri NCIMB 30242 capsules have been shown to lower cholesterol and reduce sterol absorption; however their effect on fat soluble vitamins are unknown and the main objective of this study.HypothesisThe research hypothesis is that L. reuteri NCIMB 30242 capsules would not significantly alter serum fat soluble vitamins in a randomized controlled trial.Methods127 subjects were randomized to consume L. reuteri NCIMB 30242 or placebo capsules over a 9‐week intervention period.ResultsOral supplementation of L. reuteri NCIMB 30242 capsules did not result in reduced serum vitamins A, E and â‐carotene and unexpectedly increased 25(OH)D. Despite no differences in dietary intake (P>;0.05), subjects consuming L. reuteri NCIMB 30242 showed increased serum 25(OH)D over the intervention period by 14.9 nmol/l or 25.5%, which was a significant mean change relative to placebo of 17.1 nmol/l (P=0.005) or 22.4% respectively (P=0.011). Changes in 25(OH)D were negatively correlated with hs‐CRP (r = −0.208, P=0.023).ConclusionsTo our knowledge this is the first report of increased serum 25(OH)D with oral probiotic supplementation. L. reuteri NCIMB 30242 should be considered for improving vitamin D status in individuals with CVD.
Exercise Training on Left Ventricular Interstitial Collagen in Spontaneously Hypertensive Rats
Authors: Pagan Luana Urbano , Damatto Ricardo , Cezar Marcelo , Lima Aline , Bonomo Camila , Guizoni Daniele , Martinez Paula , Gimenes Rodrigo , Okoshi Marina , Okoshi Katashi 
Published: June 2021

Systemic hypertension can cause myocardial interstitial collagen matrix remodeling and exercise may be beneficial in this process. The aim of this study was to evaluate the influence of exercise training on left ventricular interstitial collagen matrix in spontaneously hypertensive rats (SHR) before clinical evidence of heart failure.MethodsSixteen month old SHR were divided into two groups: sedentary (SED, n=8) and exercised (EX, n=8). Physical training was performed 5 times per week for 16 weeks in a treadmill. Myocardial total and soluble collagen and hydroxyproline concentrations were determined by spectrophotometry. Collagen I and III and lysyl oxidase gene expression were analyzed by real‐time PCR.StatisticsStudent's t test (p<0.05).ResultsMyocardial total and soluble collagen concentration did not differ between groups. Hydroxyproline concentration was lower in EX (0.22±0.04 vs. 0.32±0.08 μm/mg, p<0.05). Gene expression was not significant different between groups.ConclusionExercise training decreases myocardial hydroxyproline concentration in spontaneously hypertensive rats.
Deficiency of Apoptosis Inducing Factor (AIF) decreases complex I activity and increases the ROS generation in isolated cardiac mitochondria
Authors: Szczepanek Karol , Hu Ying , Lesnefsky Edward , Chen Qun 
Published: June 2021

ObjectiveGenomic downregulation of mitochondrial AIF content in Harlequin (Hq) mice increases cardiac injury during ischemia‐reperfusion (IR). We investigated if the AIF deficiency in cardiac mitochondria affects the rate of oxidative phosphorylation (OXPHOS) and the electron transport chain (ETC)‐mediated generation of reactive oxygen species (ROS).MethodsThe rate of OXPHOS, complex I activity, and the net release of H2O2 were determined in isolated mitochondria from Hq or wild type (WT) mouse hearts.ResultsDownregulation of AIF expression inhibited the rate of OXPHOS using glutamate and malate (Glu+mal) as complex I substrates (Table). The complex I activity was also decreased in Hq mouse heart mitochondria vs. WT. The net release of H2O2 was increased in Hq mitochondria vs. WT, using both complex I and complex II substrates (Succinate + rotenone, Succ+ROT).ConclusionMitochondrial AIF deficiency leads to a defect at the proximal portion of ETC and increased generation of ROS from the ETC. This setting likely contributes to increased cardiac injury in Hq mice during IR.This work was supported by the American Heart Association (QC, 11SDG5120011) and the Department of Veterans Affairs (EJL).
Role of bile acids in autophagy and alcohol‐induced liver injury
Authors: Manley Sharon , Ni Hongmin , Yang Hua , Guo Grace , Apte Udayan , Ding Wen‐Xing 
Published: June 2021

Autophagy is a lysosomal degradation process and cellular protective mechanism. Bile acids display hepatotoxicity by inducing cell death and has been shown to modulate alcohol‐induced liver injury but the mechanism is not clear. We found that Farnesoid X Receptor deficient (FXR‐/−) mice which have increased hepatic bile acid levels had impaired autophagy. This is supported by the finding that the levels of LC3‐II and p62, two proteins which are normally degraded by autophagy, are significantly higher in FXR−/− mouse livers compare to that of wild type. Because inhibition of autophagy exacerbates alcohol‐induced liver injury, we hypothesized that FXR−/− mice may have exacerbated liver injury after alcohol treatment. Indeed, alcohol treated‐FXR−/− mice had increased serum alanine aminotransferase (ALT) and hepatic triglyceride levels compared to wild type mice. Alcohol‐treatment increased the expression of autophagy genes in wild type mice, but not in FXR−/− mice, suggesting the expression of autophagy genes might require FXR. In conclusion, the impaired autophagy in FXR−/− mice may contribute to the increased alcohol‐induced liver injury.This work was supported by NIH R01 AA020518–01 (WXD) and P20 RR021940 (COBRE).
Aptamer‐Drug Conjugates for Targeted Therapy of CD30‐expressing Lymphomas
Authors: Parekh Parag A , Kamble Sanchit R , Zihua Zeng , Zu Youli 
Published: June 2021

CD30 is a biomarker for diagnosis and targeted therapy of Anaplastic Large cell lymphoma (ALCL) and Classical Hodgkin Lymphoma (CHL). Our previous studies have demonstrated specific binding of RNA aptamer to CD30 positive tumor cells. However, for in vivo targeted therapy there is a concern about biostability of the RNA aptamers.To overcome this, an ssDNA aptamer was developed via a hybrid SELEX approach using CD30‐expresing lymphoma cells and purified CD30 protein to yield the aptamer C2NP which specifically bound to CD30 expressing ALCL and CHL cells at concentrations ≤10 nm and did not react to control tumor cells. Importantly, C2NP is highly stable and more than 50% of them remained after incubation in human serum at 37°C for 24 hours, indicating the suitability for in vivo use.For targeted therapy study, C2NP was conjugated with a chemotherapeutic agent and a fluorescent reporter to form an aptamer‐drug conjugate (ADC). The specificity of ADC was confirmed by flow cytometry and intracellular delivery of chemo‐drug was observed by microscopy. Chemical conjugation of drug had no effect on aptamer binding specificity and affinity to lymphoma cells. In addition, potential therapeutic effects of the aptamer‐drug conjugate are under investigation by using cultured ALCL and CHL cell‐lines currently. This is the first study to use an aptamer‐drug conjugate for targeted therapy of CD30‐exprssing lymphomas.
Reversal of P‐glycoprotein mediated multidrug resistance by Cryptotanshinone and Dihydrotanshinone
Authors: HU Tao , Yeung John H.K. , Wang Lin , Zhou Xuelin , Or Penelope M.Y. , To Kenneth K.W. , Cho Chi Hin 
Published: June 2021

Multidrug resistance of cancer cells is an obstacle to successful cancer chemotherapy. Overexpression of P‐glycoprotein (P‐gp), an ATP‐binding cassette (ABC) membrane transporter, can mediate the efflux of drugs out of cancer cells, leading to multidrug resistance and chemotherapy failure. Therefore, development of safe and effective P‐gp inhibitors plays an important role in chemotherapy.This study investigated the reversal of P‐gp mediated multidrug resistance by several tanshinones including Tanshinone I, Tanshinone IIA, Cryptotanshinone and Dihydrotanshinone isolated from Danshen (Salvia miltiorrhiza), a traditional Chinese medicine. Bi‐directional transport assay in Caco‐2 cells showed that Cryptotanshinone and Dihydrotanshinone could decrease digoxin efflux ratio in a concentration‐dependent manner, indicating inhibitory effects on P‐gp function. Whereas, Tanshinone I and Tanshinone IIA had no effects. Moreover, Cryptotanshinone and Dihydrotanshinone could increase the intracellular accumulation of doxorubicin in P‐gp overexpressing SW620 Ad300 cancer cells. To this end using MTT assay Cryptotanshinone and Dihydrotanshinone could potentiate the cytotoxicity of doxorubicin and irinotecan in SW620 Ad300 cells as well. These findings suggest that Cryptotanshinone and Dihydrotanshinone could be used as an adjuvant therapy together with anticancer drugs in chemotherapy to improve their therapeutic effects for colon cancer.
Neuroblastoma cell proliferation involves prostaglandin E2 and subsequent β‐catenin stabilization
Authors: Jansen Sepp , Van Oppen Jessica , Hedemann Ilja , Holman Rian , Faraj Sayf , Kok Jan Willem , Diks Sander , Timens Wim , Gosens Reinoud , De Bont Eveline , Schmidt Martina 
Published: June 2021

Neuroblastoma (NBL) is a neural crest derived tumor which accounts for ±15% of pediatric cancer deaths. Despite recent efforts to elucidate the genetic background of NBL, the molecular etiology remains unclear. Recent evidence points to the cyclic‐ AMP (cAMP) elevating ligand prostaglandin E2 (PGE2) and the oncoprotein β‐catenin as two novel players in NBL. Here, we aimed to define a potential role and interplay of PGE2 and β‐catenin in survival of NBL.β‐Catenin expression was analyzed by immunohistochemistry in 41 human NBL biopsies. Further, we studied survival of 8 human NBL cell lines in response to PGE2 and cAMP elevation by the adenylyl cyclase activator forskolin.Our findings show that β‐catenin expression inversely correlates with NBL patient survival. In addition, we show that expression of a degradation‐resistant β‐catenin mutant (S33Y) increased NBL cell proliferation. Similarly, both PGE2 and forskolin enhanced proliferation, promoted GSK‐3 phosphorylation, β‐catenin stabilization and β‐catenin dependent gene transcription. In line with our hypothesis, reduction of endogenous PGE2 by a cyclooxygenase‐2 inhibitor attenuated NBL cell survival, a process being partially reversed by exogenous PGE2. We conclude that PGE2‐induced cAMP stabilizes β‐catenin and promotes NBL tumor cell survival via enhanced β‐catenin target gene transcription.This study is supported by the UMCG.
Evaluation of muscle sympathetic nerve activity in patients with chronic severe aortic insufficiency
Authors: SOUZA SILVIA B P C , Accorsi Tarso A D , Katz Marcelo , Bezerra Otavio C , Neves Gizele a , Grinberg Max B P , Consolim‐Colombo Fernanda M , Tarasoutchi Flavio B P 
Published: June 2021

The aim of this study is to evaluate the activity of sympathetic nerve sistem by microneurography in asymptomatic patients with aortic insufficiency (AoI) chronic important.Were included 10 asymptomatic patients with anatomically important AoI of rheumatic etiology with normal left ventricular function (ejection fraction>; 55%) by echocardiogram.Exclusion criteriadiabetes mellitus, renal failure, neuropathy, or beta‐blockers. A control group of normotensive volunteers (control group, n=11) with age, sex and body mass index‐ matched was included. MNSA by microneuragraphy, and blood pressure (BP) by FINOMETER® were evaluated in supine rest position. Continuous variables are described as mean ± SD and categorical variables as relative frequencies. Student t test and a multivariate analysis model were used, p <0.05 was considered statistically significant.AoI group and control group showed no statistically significant regarding age, sex and BMI. Systolic BP in AoI group was 148 +16 mmHg vs. 120±4 mmHg in control group (p = 0.0001), Diastolic BP was 60±6 mmHg in AoI and 73±3 mmHg in control group (p = 0.0001). The MSNA was in the AoI group 25±3 vs. 15±2 in the control group (p <0.001). Aortic insufficiency was associated independently with a higher MSNA (p = 0.02).AoI important chronic and asymptomatic is associated with increased MSNA.
Continuous and intermittent electrical stimulation of the aortic depressor nerve in conscious rats: time course of the hemodynamic responses
Authors: Salgado Helio , Brognara Fernanda , Dias Daniel Penteado Martins , Castania Jaci Airton , Fazan Rubens 
Published: June 2021

We investigated the time course of the hemodynamic responses to continuous (CONT) or intermittent (ON/OFF) electrical stimulation of the aortic depressor nerve (ADN) in conscious rats. Rats were implanted with electrodes around the ADN and a catheter into the femoral artery. On the next day the baseline systolic (SAP), diastolic (DAP), mean arterial pressure (MAP) and heart rate (HR) were recorded during 30 minutes and the rats were randomly assigned to CONT (0.5 mA; 0.25 ms; 30 Hz) or ON/OFF (5s ON/3s OFF; 0.5 mA; 0.25 ms; 30 Hz;) stimulation during 60 min. Changes were greater under CONT as compared to ON/OFF stimulation (SAP: −21 ± 4 vs −10 ± 2 %; DAP: −23 ± 4 vs −14 ± 3 %; MAP: −22 ± 4 vs −12 ± 3 %). In addition, under CONT stimulation the HR was reduced within the first 5 min. The hypotensive and bradycardic responses were maintained over the entire period of stimulation in the ON/OFF protocol. Nevertheless, as compared to the first 5 min, CONT stimulation showed a rapid transitory increase in DAP (72 ± 3 vs 64 ± 3 mmHg) and MAP (87 ± 3 vs 78 ± 4 mmHg). In conclusion, CONT stimulation of the ADN elicits greater hemodynamic responses as compared to the ON/OFF protocol. This finding indicates that the CONT stimulation is more effective to reduce the arterial pressure during long period of electric baroreflex activation.Financial support: FAPESP, CNPq and CAPES.
Technique‐dependent considerations when assessing racial differences in arterial baroreflex function
Authors: Keller David M , Holwerda Seth W , Credeur Daniel P , Fadel Paul J 
Published: June 2021

Examination of the arterial baroreflex (ABR) may provide insight into underlying racial differences in the development of hypertension. We compared the ability of a commonly used open loop method to assess ABR gain (i.e., modified Oxford) with a standard closed loop “spontaneous” method (sequence technique) in detecting potential racial differences. Fifteen non‐hypertensive men (7 black and 8 white, ages 18–27 yr) participated. Mod‐Ox trials were performed using 100μg iv bolus of sodium nitroprusside (NTP) followed 1min by 150μg bolus of phenylephrine (PE) during supine rest (3X per subject). Sequence technique was performed during 10min of supine rest. Overall ABR gain, while not different using modified Oxford analysis (p=0.64), was greater in blacks with sequence technique (p<0.05). In addition, ‘hypotensive’ responses were not different using the mod‐Ox, yet enhanced in blacks using sequence technique (p<0.05). For hypertensive responses, a greater gain was also found with the sequence technique (black: 28±11 vs white: 18±5 ms/mm Hg, p<0.05); however, the ABR gain for the mod‐Ox was in complete opposition with a significantly lower gain in blacks (10±4) compared to whites (16±5 ms/mm Hg, p<0.05). These findings demonstrate technique‐dependent outcomes that warrant consideration when assessing group differences in ABR function.Supported by NIH R15HL096103 (DMK) and RO1 HL093167 (PJF)