bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of diet intervention on inflammation‐related gene expression in CD14+ circulating monocytes from metabolic syndrome patients (1037.10)
Authors: Martin Lorena , Deo Simmi , Sears Dorothy 
Published: June 2021

Study objective: To examine the effects of a dietary intervention on circulating monocytes in patients with Metabolic Syndrome.Methods: In this study, we analyzed pro‐inflammatory gene expression in CD14+ circulating monocytes from metabolic syndrome subjects before, during, and after two diet interventions. The study was a randomized, single‐blind, controlled trial of a 12‐week long, 1500 calorie diet. The active diet included low glycemic index bread products, EPA/DHA fish oil capsules (2.4g EPA+DHA/day), and delphinidin polyphenol capsules (300 mg, 10,000 ORAC units/day). The placebo diet included market variety bread products, corn oil capsules, and corn starch capsules. We hypothesized that the active dietary components would act synergistically to significantly improve the inflammatory gene expression profile of the subjects as compared to placebo diet. Baseline, midpoint, and endpoint mRNA expression profiles from monocyte RNA samples were assessed for 30 obese subjects.Results: Post‐hoc analysis of real‐time quantitative polymerase chain reaction (RT‐qPCR) results to measure the expression levels of twelve inflammatory marker genes of interest revealed significant reduction in toll‐like receptor 2 (TLR2) F (1, 16) = 9.136, p < 0.01, CD11c, F (1, 16) = 12.484, p < 0.01 and tumor necrosis factor alpha (TNFα), F (1, 16) = p < 0.05 expression in circulating monocytes of active group as compared to the placebo group, p <0.05.Conclusions: This study was part of a parent clinical trial showing that average fasting insulin and HOMA‐IR improved significantly in the active group but not the placebo group. This monocyte gene expression data will contribute to painting the picture of how the composition of a low calorie diet modulates inflammation and insulin sensitivity.Grant Funding Source: Supported by P. Robert Majumder Charitable Foundation, UCSD CTRI (DDS), NIH (SKD), and Zone labs.
High rates of riboflavin deficiency in women of childbearing age in Cambodia and Canada (1041.12)
Authors: Whitfield Kyly , McCann Adrian , Karakochuk Crystal , Talukder Aminuzzaman , Ward Mary , McNulty Helene , McLean Judy , Green Tim 
Published: June 2021

High rates of riboflavin deficiency in women of childbearing age in Cambodia and Canada Whitfield, KC1, McCann, A2, Karakochuk, C1, Talukder, A3, Ward, M2, McNulty, H2, McLean, J1, Green TJ1 (1) Department of Food, Nutrition, and Health, University of British Columbia, Canada (2) Northern Ireland Centre for Food and Health, University of Ulster, Northern Ireland (3) Helen Keller International, Phnom Penh, Cambodia As an integral component of the coenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), riboflavin is essential for metabolic homeostasis. Limited evidence is available comparing riboflavin status among individuals from developed and developing countries.We conducted two cross‐sectional studies with apparently healthy non‐pregnant, non‐lactating women of childbearing age (20‐45y), on a representative sample from urban Phnom Penh (n=146) and rural Prey Veng (n=156), Cambodia, and a convenience sample of urban women in Vancouver, Canada (n=51). As a functional biomarker of riboflavin status, erythrocyte glutathione reductase activity coefficient (EGRac) was measured.Among Cambodian women, riboflavin deficiency (EGRac 蠅1.4) was prevalent (Prey Veng, 82%; Phnom Penh, 78%). Although a significantly higher proportion of Canadian women were riboflavin sufficient (EGRac 蠄1.3; p<0.001), 67% of Canadians had a suboptimal riboflavin status (EGRac >1.3).The data suggests suboptimal riboflavin status and deficiency may be widespread in both developed and developing countries and merits further investigation.Grant Funding Source: Supported by the University of British Columbia Vitamin Research Fund
Serum 25‐hydroxy vitamin D is associated with blood total cholesterol and diastolic blood pressure in a young multi‐ethnic group living in South Florida (1041.15)
Authors: Ajabshir Sahar , Exebio Joel , Zarini Gustavo , Nayer Ali , Vaccaro Joan , Shaban Lemia , Huffman Fatma 
Published: June 2021

Objective: The aim of this study was to investigate the relationship between serum 25‐hydroxy vitamin D, total cholesterol and blood pressure (BP) among young multi‐ethnic participants living in South Florida.Methods: This cross‐sectional study included 80 young adults, males (n=42) and females (n=38), ages 18‐36 years recruited from Florida International University campus. Serum 25‐hydroxy vitamin D and TC were measured by ELISA method. Systolic and diastolic BPs were measured by an automated monitor. Weekly total sun exposure and daily vitamin D intake were calculated from validated sun exposure and food frequency questionnaires respectively. A multi‐linear regression model was run, adjusting for age, gender, body mass index, systolic BP, daily vitamin D intake, total weekly sun exposure and tobacco use.Results: Total cholesterol (P= 0.020) and diastolic blood pressure (P= 0.025) were negatively associated with serum 25‐hydroxy vitamin D. This association remained significant after controlling for covariates (B= ‐0.074, P=.045 for total cholesterol, B= ‐0.421, P= ‐0.018 for diastolic blood pressure). The model explained 18.4% of the variation in serum 25‐hydroxy vitamin D.Conclusion: The results of this study suggest that high total blood cholesterol and diastolic blood pressure may be associated to low serum 25‐hydroxy vitamin D level. Interventions are needed to confirm these results.Grant Funding Source: Supported by NIH/NIDDK sponsored grant.
A randomized controlled trial of vitamin D supplementation in pregnancy: effects on vitamin D status and clinical outcomes (1041.5)
Authors: Zerofsky Melissa , Jacoby Bryon , Stephensen Charles 
Published: June 2021

Vitamin D status in pregnancy is associated with health outcomes for mother and infant. The current recommendation for vitamin D intake during pregnancy may be insufficient to raise serum 25‐hydroxyvitamin D (25OHD) to optimal levels. This study evaluated the effect of two treatment regimens on vitamin D status and clinical outcomes. 57 pregnant women at risk for low 25OHD were randomized to treatment (2,000 IU vitamin D3/d) or control (400 IU/d) from <20 wk gestation until delivery. 51 women completed the study. Plasma vitamin D metabolites were measured at <20 wk, 26 wk, and 36 wk gestation. 25OHD was significantly greater in the treatment group at both 26 (104.515.7 vs. 86.320.2 nmol/L) and 36 wk (115.820.1 vs. 85.618.0 nmol/L; p<0.05). The treatment group had a larger change over pregnancy than the control (p<0.0001), and a significantly greater proportion achieved a 25OHD >75 nmol/L by 36 wk (96% vs. 73.1%; p=0.02). Plasma 1,25‐dihydroxyvitamin D increased more in the treatment than the control group between baseline and 26 wk (p<0.01) and 36 wk (p<0.01). Maternal clinical outcomes, including blood pressure and glucose tolerance, did not differ between groups. Infants born to mothers in the treatment group had a marginally (p=0.06) greater birth weight (3,668431 g) than those in the control group (3,379557 g). A daily dose of 2,000 IU is effective at improving vitamin D status in pregnant women.Grant Funding Source: Supported by UC Davis CTSC Vision Grant, UL1 TR000002 and USDA‐ARS
Arginase 1 regulates SIRT1 activity and endothelial senescence in diabetes (1051.1)
Authors: Toque Haroldo , Bhatta Anil , Yao Lin , Caldwell Ruth , Caldwell R. 
Published: June 2021

Premature senescence in endothelial cells (EC) has emerged as a factor in vascular endothelial dysfunction (VED) during diabetes and other cardiovascular diseases. Diabetes‐induced VED involves elevated arginase (ARG) activity. Reduced levels/activity of sirtuin 1 (SIRT1, a histone deacetylase essential for EC self‐renewal and resistance to stressors) have been linked to premature senescence. We examined the roles of ARG and SIRT1 in diabetes‐induced premature EC senescence by studies using EC specific‐ARG1 knockout (KO) mice and bovine aortic and human coronary EC and WT mouse aorta transduced with ARG1 cDNA (24 hr) or exposed to high glucose (HG, 25 mM, 72 hr). We observed that diabetic or ARG1 transduced aorta exhibited premature EC senescence [measured as senescence‐associated β‐galactosidase (SA‐β‐gal) activity], decreases in SIRT1 activity/expression and VED accompanied by increases in ARG activity and reduced NO production. These effects were not seen in diabetic KO mice with EC specific deletion of ARG1. Furthermore, EC transduced with ARG1 or treated with HG showed marked decreases in SIRT1 activity and NO production which were accompanied by significant increases in activity of ARG and SA‐β‐gal. Hence, reducing ARG1 activity/expression preserves SIRT1 levels, maintains NO production and prevents premature EC senescence and thus has therapeutic potential in attenuating diabetes‐induced VED.Grant Funding Source: AHA Scientific Development Grant
Expression and localization of alpha‐1 adrenergic receptors in aorta of diabetic Wistar Kyoto and spontaneously hypertensive rats (1051.18)
Authors: Rodriguez Jessica , Reséndiz‐Albor Aldo , Rosales‐Cruz Erika , Hong Enrique , Villafaña Santiago 
Published: June 2021

Hypertension and diabetes are multifactorial diseases that frequently coexist and exacerbate each another. During the development of diabetes the impairment of noradrenergic system has been reported especially to the response mediated by alpha‐1 receptors. Although their participation in the development of cardiovascular complications is still controversial some studies have found increased or diminished response to the vasoconstrictive effect of noradrenaline in a time‐dependent manner of diabetes. Thus, the aim of this work was to investigate possible changes in the expression or localization of alpha‐1 adrenergic receptors (alpha‐1A and alpha‐1D) in aorta of rat after 4 weeks of the onset of diabetes. In order to be able to examine the expression of alpha‐1 adrenergic receptors immunofluorescence procedure was performed in túnica intima and media of hystological sections of aorta. Fluorescence was detected by a confocal microscopy. Our results suggest that both receptors showed a higher density in tunica intima and tunica media of SHR aorta compared with WKY rats. Whereas 4 weeks diabetes increases the expression of the receptors dependently of the aortic región and the receptor subtype wherein expression of the alpha‐1A receptor is increased in the intima while the alpha‐1D receptor in tunica media. In conclusion early diabetes modifies the expression of alpha‐1 adrenergic receptors in aorta of both WKY and SHR strains in a different way.Grant Funding Source: CONACYT CB‐2012‐01‐183660/ COFAA
Positive KCa channel gating modulators with selectivity for KCa3.1 (1057.6)
Authors: Brown Brandon , Coleman Nichole , Oliván‐Viguera Aida , Köhler Ralf , Wulff Heike 
Published: June 2021

Intermediate and small‐conductance Ca2+ activated K+ (KCa) channels regulate membrane excitability and Ca2+ signaling. Pharmacological activation of these voltage‐independent channels has therefore been suggested for the treatment of various diseases. While KCa2 activators can potentially reduce neuronal excitability in CNS disorders, selective KCa3.1 activators could be useful as endothelial targeted antihypertensives. KCa channels are gated by Ca2+ binding to a constitutively associated calmodulin at the C‐terminus. Recent work by Zhang et al. (Zheng M. 2012 Nat Commun 3:1021) demonstrated that the benzimidazolone 1‐EBIO binds at the interface of the CAM N‐lobe and the calmodulin binding domain (CAMBD) of KCa2.2. Mutations of A477V/L480M and A477I in KCa2.2 were shown to increase and decrease potency of 1‐EBIO, respectively. Here we report that the same mutations (A625V/L628M and A625I) in KCa2.3 also alter the potency of KCa2/3 activators of the benzothiazole class such as SKA‐31. However, like 1‐EBIO and NS309, SKA‐31 suffers from a lack of selectivity between KCa3.1 and KCa2 channels. Via a structure activity relationship study we have optimized the pharmacophore of SKA‐31 and have now identified several compounds that display 40 to 160‐fold selectivity for KCa3.1 over KCa2.3. SKA‐121, a compound generated through an isosteric replacement approach, lowers blood pressure in mice as determined by telemetry without exerting KCa2 channel mediated effects on heart rate.Grant Funding Source: Supported by a NIGMS funded T32GM099608
Novel GABAA‐rho1 interactions with acid sensing ion channel ligands (1059.3)
Authors: Snell Heather , Gonzales Eric 
Published: June 2021

γ‐ amino butyric acid (GABA) is the major inhibitory neurotransmitter in the vertebrate brain, and targets the ionotropic GABAA receptors. GABAC, or GABAA‐rho, is a subclass of GABAA receptors composed entirely of rho (ρ) subunits and are located on the axonal terminal of retinal bipolar cells, where it not only exhibits a tonic inhibitory current, but also regulates the GABA‐A and other GABAA‐rho synaptic currents (Jones et al 2011). GABAA‐rho exhibits unique properties, such as insensitivity to select antagonists of the heteromeric GABAA receptors (Korpi et al., 2002). A group of ligands, which possess a guanidine group, have been shown to influence GABAA receptors. These compounds, such as (S)‐2‐Guanidinopropionic acid and guanidine acetic acid were competitive antagonists for the GABAA‐rho1 receptor. Other guanidine compounds that are acid sensing ion channel (ASIC) ligands, might also exhibit unique effects on the GABAA‐rho1 receptor. We hypothesize that these ASIC ligands will exhibit unique intrinsic activities on the GABAA‐rho1 receptor, which is different from that of the heteromeric GABAA receptor. The human GABAA‐rho1 receptors were expressed in HEK‐293T cells, and activity was analyzed using whole cell patch‐clamp electrophysiology. When co‐applied with GABA and compared to the GABA concentration profile, one ligand was found to decrease the maximal response, with no change in the GABA EC50. This indicates characteristics of non‐competitive inhibition, while a different ligand shifted the GABA EC50 to lower GABA concentrations, suggesting this guanidine compound is a positive allosteric modulator. When applied alone, it failed to directly activate GABA rho1 receptors. These contrasting effects suggest that these ligands act at two binding sites within the GABAA‐rho architecture. Future experiments will focus on additional characterization of these novel effects on GABA rho receptors and offer a novel chemical structure to design novel GABAA‐rho therapeutics.Grant Funding Source: Supported by: Welch Foundation Grant No: BK‐1736, NIH training grant: NBA T32 AG020494
BPC 157 antagonized the general anesthetic potency of thiopental and reduced prolongation of anesthesia time induced by L‐NAME/thiopental combination (1061.3)
Authors: Zemba Mladen , Zemba Cilic Andrea , Balenovic Igor , Cilic Matija , Radic Bozo , Suran Jelena , Drmic Ivan , Stambolija Vasilije , Murselovic Tamara , Katancic Holjevac Jadranka , Uzun Sandra , Djuzel Viktor , Seiwerth Sven , Sikiric Predrag 
Published: June 2021

We hypothesized the general anesthetic thiopental effect depending on NO‐related mechanisms, consequently counteracted by stable gastric pentadecapeptide BPC 157.(i) To determine the general anesthetic effect of thiopental and possible counteraction depending on BPC 157 administration, all rats received intraperitoneally thiopental (20, 30, 40 mg/kg) while medication (BPC 157 (10 μg/kg, 10 ng/kg, 10 pg/kg) was given intraperitoneally at 5 min before thiopental. (ii) To determine NO‐related mechanisms, all rats received intraperitoneally thiopental 40 mg/kg while BPC 157 (10 μg/kg), L‐NAME (10 mg/kg), L‐arginine (30 mg/kg) were applied alone and/or combined. BPC 157 was given at 25 min before thiopental while L‐NAME, L‐arginine, alone and/or combined, were applied at 20 min before thiopental.(i) BPC 157 (10 ng/kg and 10 μg/kg), caused significant antagonism of general anesthesia produced by thiopental with a parallel shift of the dose‐response curve to the right. (ii) L‐NAME. Thiopental‐induced anesthesia duration was tripled. L‐arginine. Active only given with L‐NAME or BPC 157: habitual thiopental anesthesia time not influenced; potentiating effects of L‐NAME lessened, not abolished; shortening effect of BPC 157: abolished. BPC 157 and L‐NAME. Potentiating effects of L‐NAME was abolished. L‐NAME and L‐arginine and BPC 157. L‐NAME+L‐arginine+BPC 157 rats exhibited values close to those in BPC 157 rats.Thiopental general anaesthesia is simultaneously manipulated in both ways with NO‐system activity modulation, L‐NAME (prolongation) and BPC 157 (shortening/counteraction). BPC 157 and L‐arginine might serve two NO‐system pathways, more or less active, alternatively activated.Grant Funding Source: Supported by Grant 108‐ 1083570‐3635, Croatia
Tumor‐targeting and anti‐tumor activity of anti‐claudin‐3/‐4 antibody (1062.7)
Authors: Kimura Yuka , Li Xiangru , Iida Manami , Tada Minoru , Ishii Akiko , Watari Akihiro , Fukasawa Masayoshi , Yagi Kiyohito , Kondoh Masuo 
Published: June 2021

Claudins (CLDNs) comprise a tetra‐transmembrane protein family with ~20 members, which are located in the lateral membrane between adjacent epithelial cells. Because of loss of cellular polarity during malignant transformation, CLDN often migrates from the lateral membrane and becomes exposed on epithelial cell surfaces. CLDN3 and CLDN4 are targets for tumor therapy because they are overexpressed in various malignant tumors. We previously optimized a protocol for immunization with CLDN and developed 8 rat anti‐CLDN4 monoclonal antibodies, one of which recognized both CLDN3 and CLDN4. In this study, we focused on the CLDN3/4 antibody. The CLDN3/4 antibody showed high affinity for CLDN4 (KD value: 4.3 nM). We fluorescently labeled the CLDN3/4 antibody and intravenously injected it into mice bearing tumors (human colon cancer Lovo cells, or human gastric cancer MKN74 cells). The CLDN3/4 antibody accumulated in tumor tissues and attenuated tumor growth without apparent adverse effects in the Lovo‐ and MKN74‐bearing mice. Furthermore, CLDN3/4 antibody activated the Fcγ receptor in vitro. Therefore, the CLDN3/4 antibody may exert its anti‐tumor activity through antibody‐dependent cellular toxicity. These findings suggest that the CLDN3/4 antibody is a candidate anti‐tumor agent.Grant Funding Source: supported by the Ministry of Health, Labor, and Welfare of Japan
Cerebral blood flow regulation during blood loss compared to lower body negative pressure in humans (1068.9)
Authors: Barnes Jill , Johnson Blair , Convertino Victor , Joyner Michael , Rickards Caroline 
Published: June 2021

Lower body negative pressure (LBNP) is often used to simulate blood loss in humans. However, it is unknown if the effects of actual blood loss (BL) on cerebral blood flow regulation is analogous to simulated blood loss during LBNP. Nine healthy men (32±6 y) were studied at baseline, during 3 levels of LBNP (5 min each at ‐15, ‐30, ‐45 mmHg), and during 3 levels of blood loss (5 min each at 333, 667, 1000 mL). LBNP and BL conditions were randomized. Intra‐arterial mean arterial pressure (MAP) was similar during LBNP compared with BL (p>0.20). Central venous pressure (CVP; 2.8±0.7 vs. 4.0±0.8, 1.2±0.6 vs. 3.5±0.8, 0.2±0.9 vs. 2.1±0.9 mmHg for level 1, 2, and 3; p<0.01) and stroke volume (71±4 vs. 80±3, 60±3 vs. 74±3, 51±2 vs. 68±4 mL for level 1, 2, and 3; p<0.01) were lower during LBNP compared with BL. Despite differences in CVP, middle cerebral artery velocity (MCAv) and cerebrovascular conductance index (CVCi) were similar between LBNP and BL at each level (MCAv at level 3: 62±6 vs. 66±5 cm/s; p=0.37; CVCi at level 3: 0.72±0.05 vs. 0.73±0.05 cm/s/mmHg; p=0.29). Furthermore, the slope of the relationship between MAP and MCAv was not different between LBNP and BL (1.06 vs. 1.07 cm/s/mmHg). Our results suggest that the cerebral hemodynamic responses to LBNP are similar to actual blood loss.Grant Funding Source: Supported by U.S. Army MRMC Combat Casualty Care Research Program Grant # W81XWH‐11‐1‐0823
Dynamic and static factors predicting vasomotor reactivity in forced hypocapnia (1070.8)
Authors: Müller Martin , Österreich Mareike 
Published: June 2021

Objectives: In mechanically ventilated patients intensive hyperventilation can be detrimental. Using transfer function (TF) estimates we were interested in which Parameter could be used for monitoring autoregulation in this condition.Methods: 18 healthy persons (9 women; mean age 32 +‐9 years) underwent simultaneously recordings of blood flow velocity (BFV) by means of transcranial Doppler sonography, blood pressure and endtidal pCO2 (ETpCO2) during 4‐5 minute periods of normoventilation and voluntary hyperventilation. Breath holding (BH) as long as possible started immediately at the end of hyperventilation. TF and Coherence were calculated using Welsh's periodogram method. Mean values were calculated for phase and gain in the very low frequency (vlf) range (0.02‐0.07 Hz), low frequency (lf) range (0.07‐0.15 Hz) and high frequency (hf) range (0.15‐0.40 Hz). VMR was indicated by: 1. VMR% = [BFVnormov‐(BFVbh‐BFVhyperv)/BFVnormov]* 100; 2. BHI= VMR% divided by time of BH.Results: Mean BP was 83±10 mm HG in normoventilation (ETpCO2 0.53 ±0.05 Vol%), 84±11 in hyperventilation (ETpCO2 0.36±0.05) and 82±14 at BH release (ETpCO 0.56 ±0.06); BFV was 59±19 cm/sec, 47±17 and 78±28 cm/sec respectively. Stepwise regression analysis indicated: 1. VMR% was significantly related to ETpCO2 (r=0.50, p<0.01), lf gain (r=0.40, p<0.01) and hf gain (r=0.63, p<0.001) each under hypocapnia; 2. BHI was significantly related to lf phase (r=‐0.58; p=0.01) and lf gain (r=0.63; p<0.001) under hypocapnia and to hf gain (r=0.49; p<0.01) under normocapnia.Conclusion: VMR% and BHI remained related to blood pressure derived gain function. The negative correlation between phase and BHI may give a first hint why extreme hypocapnia can be detrimental to patients under mechanical ventilation
Inhibition of high salt‐induced activation of NLRP3 inflammasome by mesenchymal stem cell transplantation in the renal medulla in Dahl S rats (1074.7)
Authors: Li Xiaoxue , Zhu Qing , Conley Sabena , Hu Junping , Li Pin‐Lan , Li Ningjun 
Published: June 2021

Activation of NALP3 inflammasome has been shown to be involved in various renal pathological conditions. It remains unknown whether renal NALP3 inflammasome activation participates in the abnormal renal response to high salt diet in Dahl salt sensitive rats. In addition, whether inhibition of NALP3 inflammasome activation contributes to the renal protective actions of stem cells is not clear. The present study detected the response of NALP3 inflammasome to high salt intake and determined the effect of mesenchymal stem cell (MSC) transplantation on inflammasome activation. Immunostaining showed that 3 essential components of the NALP3 inflammasome, NALP3, ASC and caspase‐1, were all mainly present in distal tubules and collecting ducts. Interestingly, the renal medullary mRNA and protein levels of these inflammasome components were remarkably increased by 2‐4 fold in response to high salt intake in Dahl S rats, while remained no change in normal rats. High salt‐induced increases of renal medullar inflammasome were significantly blocked by MSC transplantation into the renal medulla compared with control cell in Dahl S rats. These data suggested that high salt‐induced activation of renal medullary inflammasome may contribute to the renal medullary dysfunction in Dahl S rats and that inhibition of inflammasome activation may be one of the mechanisms for the protective effects of stem cells in the renal medulla.Grant Funding Source: HL089563 and HL106042