bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of pattern of pulse consumption on postprandial glycemic, insulinemic and appetite responses in the second meal: a pilot study
Authors: Osei-Boadi Katherene , Campbell Wayne W. , McCrory Megan A. 
Published: June 2021

BackgroundPulses (beans, peas, lentils) contain slowly absorbed and indigestible carbohydrates. We hypothesize that the specific pattern of pulse consumption across meals affects glycemic, insulinemic and appetite responses during the second meal.MethodsSix subjects (BMI 25–35 kg/m2; aged 21–55 y) consumed ½c pulses distributed across lunch (L) and dinner (D) in 4 patterns in random order with testing 1x/wk for 4 wk. The L, D patterns were: ½c,0c; 0c,½c; ¼c,¼c and 0c,0c (control). Meals provided 30% of energy requirement and were matched for macronutrients, volume and palatability. The L and D were separated by 4h and measurements were continued for 4h post D consumption. Peak and AUC significant (p ≤ 0.05) results are reported here.ResultsPEAK glucose and insulin concentrations were lower after D relative to L (D PEAK as % of L: 94% (glucose) and 86% (insulin) among all patterns. The second meal PEAK insulin (p≤0.02), was lowest for the ¼c,¼c treatment (D as % of L: 65±4% for ¼c,¼c vs. 85±7 to 91±10% for the other patterns). Hunger AUC also differed by pattern (p=0.04) and was lowest for the 0c,½c treatment at D relative to L (75±8% vs. 88±6 to 94±9%), while the pattern of pulse ingestion did not influence desire to eat or fullness responses.ConclusionThough preliminary, these results suggest that consuming ¼c of pulses each at L and D may lower second meal glycemic and insulinemic responses.Grant Funding Source: USDBC and NIH RR025761
A blend of acacia gum, fructan‐type fibers, and outer pea fiber exhibits lower gas production compared to other fiber blends in vitro
Authors: Klosterbuer Abby , Noack Jacqueline , Timm Derek , Thomas William , Slavin Joanne 
Published: June 2021

Fiber sources differ in a number of physicochemical properties, and certain combinations may yield more desirable physiological effects. Potential benefits include normalized bowel function, increased short chain fatty acid (SCFA) production and beneficial changes in gut microbiota. Negative side effects may include excess gas production leading to intolerance. We hypothesized that a 50:50 blend of fermentable and nonfermentable fibers (Blend 1) would attenuate gas production while achieving benefits similar to more fermentable blends. The fermentation profiles of Blend 1 (fructooligosaccharide (FOS), inulin, acacia gum (AG), and outer pea fiber), Blend 2 (short chain FOS, carboxymethylcellulose, AG, oat hull and soy fiber), and Blend 3 (soy polysaccharide, cellulose, AG, inulin, oligofructose, and resistant starch) were examined using an in vitro batch fermentation model. Triplicate samples were removed at 4, 8, 12, and 24 h for analysis of gas, pH and SCFAs. Blend 1 produced significantly less gas than Blend 2 and Blend 3 (p<0.05), and had higher pH values (p<0.05). Production of total and individual SCFAs was similar among blends. In conclusion, fermentation of Blend 1 resulted in less gas while achieving similar SCFA production as other blends. These results may help predict health benefits and tolerance in vivo.Research was supported by Nestlé Health Science.
Uptake of beta‐carotene by the maternal‐fetal barrier: influences of maternal vitamin A regimens and its mechanisms
Authors: Shete Varsha , Wassef Lesley , Quadro Loredana 
Published: June 2021

Synthesis of vitamin A by cleavage of β‐carotene, its most abundant precursor in human diet, is regulated by nutrient availability in adult tissues. Intact β‐carotene is transported in association with various lipoprotein particles in circulation. Local de novo biosynthesis of retinoids from β‐carotene can be an important source of retinoids during embryonic development. Retinoids, especially transcriptionally active retinoic acid, are essential for normal embryonic development.This study examines effects of different maternal vitamin A regimens on uptake of supplemented β‐carotene by maternal‐fetal barrier. Wild‐type mice were maintained on diets containing sufficient, deficient and excess amounts of vitamin A during pregnancy. At 13.5 days of gestation, dams were supplemented with 10–30 μg/gbody weight of β‐carotene by intraperitonial injection. Maternal serum, liver, placenta, embryos were collected after 24 hours and analyzed by HPLC. Pregnant females injected with vehicle were controls.Well detectable β‐carotene levels were observed in maternal serum, liver, placenta and embryos in all supplemented mice. Serum and liver β‐carotene levels were unaltered under different vitamin A regimens. Embryonic β‐carotene levels were reduced when dams were maintained on vitamin A‐excess diet, but placental levels were not altered under any of the dietary regimens. This suggests a protective action of placenta that limits the transfer of β‐carotene from maternal circulation to embryo under vitamin A excess conditions. mRNA expressions of placental LDL receptor, SRBI (HDL receptor) were unchanged upon β‐carotene supplementation, however LRP1 (chylomicron remnants receptor) was dramatically downregulated upon β‐carotene supplementation, at least when dams were on vitamin A‐sufficient diet.Grant Funding Source : NIH
Olfactory manganese uptake in Hfe knockout mice, a model of iron overload
Authors: Kim Jonghan , Wessling-Resnick Marianne 
Published: June 2021

Iron deficiency increases dietary Fe absorption due to up‐regulation of divalent metal transporter‐1 (DMT1) in intestinal epithelium. DMT1 also transports Mn and we have shown iron deficiency enhances olfactory Mn uptake to the brain due to iron‐responsive regulation of DMT1 in olfactory epithelium. Understanding the influence of iron homeostasis on olfactory Mn uptake is important due to the neurotoxicity of airborne metal. Whether iron loading alters olfactory Mn uptake is unknown. Hereditary hemochromatosis, an iron overload disease associated with excessive intestinal Fe absorption, is commonly caused by loss of HFE gene function. We have characterized Mn pharmacokinetics in Hfe knockout mice after intravenous and intranasal 54Mn administration. Hfe−/− mice had higher serum and liver iron than Hfe+/+mice, consistent with iron overload status. In contrast, Hfe−/− mice displayed lower blood Mn levels. After intravenous injection, Hfe−/− mice cleared 54Mn from the blood more rapidly than Hfe+/+mice while 54Mn distribution to the brain was similar. However, after intranasal instillation 54Mn brain levels in Hfe−/− mice were elevated indicating olfactory uptake to the brain is enhanced by iron loading. The possible role of DMT1 and other metal transporters in enhanced olfactory Mn absorption to the brain due to HFE‐associated iron loading should be further studied. Supported by NIH DA027030 and ES017781.Grant Funding Source: NIH
Iron overload upregulates the expression of regenerating isletderived family genes in rat pancreas
Authors: Coffey Richard , Nam Hyeyoung , Knutson Mitchell 
Published: June 2021

Iron overload is associated with an increased incidence of hyperglycemia and diabetes resulting from beta cell destruction. The aim of the present study was to identify genes that are regulated by iron in the pancreas. Sprague‐Dawley rats were fed modified AIN‐93G diets that were either iron deficient, adequate, or overloaded for 3 wk. Microarray analysis of RNA isolated from pancreas revealed that the most upregulated mRNAs by iron overload were the regenerating islet‐derived genes (Reg) Reg1a, Reg3a, and Reg3b, which are associated with islet cell regeneration and diabetogenesis. Quantitative RT‐PCR analyses of these genes confirmed that their mRNA levels were more than 20 fold higher in iron overload relative to controls. These data suggest that Reg mRNAs may be sensitive indicators of pancreatic beta cell stress during iron overload. To investigate the effect of iron per se on Reg gene expression, INS1 cells, a rat pancreatic beta cell line, were incubated with or without 200 μM Fe‐NTA for 48 h. We found that Reg mRNA expression was unaffected by iron, suggesting that iron loading of beta cells is not responsible for elevated Reg expression in iron‐loaded pancreas. Funded by NIH.Grant Funding Source : NIH
Copper Transport by Divalent Metal Transporter 1 (Dmt1) Under Low Iron Conditions
Authors: Jiang Lingli , Collins James F. 
Published: June 2021

Many human and animal studies have shown that serum and liver copper levels increase during iron deficiency. This phenomenon could involve enhanced copper transport in the small intestine. During iron deficiency, when iron absorption increases dramatically, divalent metal transporter 1 (Dmt1) expression is strongly induced. Whether Dmt1 can transport copper has not been definitively answered. These studies were designed to test the hypothesis that Dmt1 transports copper during low iron states, when it is strongly induced and competing iron atoms are low. A doxycycline (DOX) inducible Dmt1 overexpression system in HEK‐293 cells was utilized to assess this possibility (developed by Dr. Michael Garrick, SUNY Buffalo). Induction of Dmt1 by DOX was confirmed by qRT‐PCR, immunoblot analysis, immunocytochemistry and 59Fe uptakes studies. In DOX treated cells with confirmed Dmt1 overexpression, 64Cu uptake was not different from untreated cells. However, a significant increase in copper uptake was noted (~5‐fold) when cells were treated with DOX in the presence of an iron chelator (as compared to DOX only treated cells). It is thus concluded that under control conditions, Dmt1 does not transport copper, but that it may be involved in copper transport under low‐iron conditions.Grant Funding Source : NIH grant 1R01 DK074867
Neutrophil infiltration related to the methotrexate‐induced intestinal barrier dysfunction
Authors: Horie Toshiharu , Asada Chiaki , Kakigawa Naoko , Sekine Shuichi 
Published: June 2021

ObjectiveMethotrexate (MTX) is used for the treatment of acute leukemia, rheumatoid arthritis and some intraosseous sarcomas. It causes severe side effects like mucosal inflammation, nausea and diarrhea. We found that MTX‐induced ROS resulted in neutrophil (PMN) accumulation and migration in rat intestine. MTX‐induced secretion of inflammatory cytokines seemed to be a triggering factor for the PMN migration. Thus, we built the in vitro assay system for PMN migration and studied the molecular mechanism.MethodsT84 cells derived from human colon carcinoma were seeded on to the lower side of inverted transwell and cultured for 3 weeks. PMNs isolated from human venous blood were applied to the upper chamber of transwell. PMNs in the lower chamber were evaluated by myeloperoxidase (MPO) activity.ResultsPMN number in the lower side was increased by adding MTX treated conditioned medium, but not changed by MTX exposure alone. IL‐8 mRNA expression was increased in a time‐dependent manner. IL‐8 secretion into MTX treated conditioned medium was increased. PMN migration was suppressed by IL‐8 neutralizing antibody, but not by control IgG. Treatment with SB203580, a p38 MAPK inhibitor regulated the MTX‐induced PMN transmigration.ConclusionsMTX caused PMN infiltration across T84 monolayer, which was caused by secreted IL‐8. It was likely triggered by IL‐1β production and p38 MAPK signal pathway.
Doxycycline protects against right ventricular dysfunction and dilatation caused by acute pulmonary thromboembolism
Authors: Neves Evandro Manoel Neto , Santos Ozelia Sousa , Ferraz Karina Coutinho , Ceron Carla Speroni , Romano Minna Dias , Gali Luis Gustavo , Maciel Benedito Carlos , Santos Jose Eduardo Tanus 
Published: June 2021

We examined whether pretreatment with doxycycline (a matrix metalloproteinase MMP inhibitor) protects against acute pulmonary thromboembolism (APT)‐induced right ventricular dysfunction and dilatation.APT (350 mg/kg of autologous blood clots) increased mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance index (PVRI) by approximately 186% and 196% respectively. Ecocardiography showed that right ventricle (RV) diameter increased in animals with APT (from 10.7±0.8 to 18.3±1.6 mm, P<0.05), but not in embolized animals pretreated with doxycycline at 10 mg/kg i.v. (from 13.3±0.9 to 14.4±1.0 mm, P>0.05). Dobutamine stimulation induced minor improvements in RV function in embolized animals. However, doxycycline improved the RV contractile reserve. APT increased serum cardiac troponin I concentrations and RV gelatinolytic activity, and doxycycline prevented theses increases (P<0.05).These results suggest that MMPs are involved in APT‐induced cardiomyocyte injury, RV dysfunction and dilatation, and degrade contractile proteins. Doxycycline improves the responses to dobutamine during APT.Funded by FAPESP, CNPq, and CAPES (Brazil).
Extravascular platelets in corneal microvascular inflammation: a potential determinant of recovery from wound injury
Authors: Rumbaut Rolando , Li Zhijie , Burns Alan R , Smith C Wayne 
Published: June 2021

The notion that platelets extravasate across inflamed microvessels is not well appreciated and their functional role is unknown. Recently, we reported evidence of extravascular platelets surrounding inflamed venules in a mouse model of corneal wound injury, and of a functional role for platelets in nerve recovery in this model. Whether extravascular platelets are required for nerve recovery remains unclear. In this study we assessed the relationship between microvascular platelet recruitment (intra vs. extravascular, at 12 h) and nerve recovery (at 96 h) following wound injury. We studied wild type (WT) mice, and mice deficient in either ICAM‐1 or gamma‐delta T cells. Nerve recovery was reduced by ~50% in both strains of deficient mice. Interestingly, the number of intravascular platelets was comparable among all strains, while the number of extravascular platelets was markedly reduced (by > 85%) in mice deficient in ICAM‐1 and gamma‐delta T cells. These data suggest a functional role for extravascular platelets in nerve recovery following corneal injury.Support: NIH EY018239, EY17120, HL079368
Cerebral Compliance Changes With Sympathetic Activation During Cold Pressor Test
Authors: Witkowski Jaclyn , Falvo Michael , Blatt Melissa , Jasien Jessica , Deegan Brian M , OLaighin Gearoid , Serrador Jorge M 
Published: June 2021

The role of sympathetic activation on arterial compliance has yet to be examined. This study examined cerebral flow velocity and cerebral compliance in response to sympathetic activation.Healthy subjects (n=13) performed a cold pressor test in which their forearms were immersed in a bucket of ice water for up to 3 minutes. Cerebral flow velocity (CFV) (middle (MCA), anterior cerebral (ACA), vertebral arteries (VA), external carotid), blood pressure, and end‐tidal CO2 were measured. Data was collected at baseline, first and final 15 sec of immersion.Compared to initial immersion, CFV increased the most in the last 15 sec of the protocol: ACA (+9.5±3.2%, P<0.02), MCA (+10.0±2.8%, P<0.02), VA (+15.4±4.6%, P<0.02). At the end of the protocol, significant increases in blood pressure were seen (+15.5±2.5 mmHg, P<0.001). Pulse wave velocity (PWV) increased in the periphery from baseline and through each time point: ACA (7.2±0.4 to 8.5±0.8 to 8.5±0.7 m/s); MCA (7.2±0.4 to 9.9±1.6 to 9.2±0.6 m/s); VA (6.7±0.5 to 7.0±0.4 to 8.5±1.4 m/s).Findings suggest that increasing sympathetic activity does not cause cerebral vasoconstriction, but increases CFV while reducing arterial compliance. Sympathetically mediated reductions in compliance may be an adaptive mechanism to enhance pressure transmission to the brain when humans are upright and pressure at the brain is lower due to the hydrostatic gradient. Supported by NASA/NIH.
Role of Adenosine A1 Receptors in Regulation of Arteriolar Responses to Adenosine and Angiotensin II
Authors: Gao Xiang , Carlström Mattias , Fredholm Bertil , Persson Erik 
Published: June 2021

OBJECTIVEAdenosine (Ado) mediates tubuloglomerular feedback, whereas AngII and NO are important modulators. A1‐deficiency abolish TGF and diminish effectiveness of L‐NAME and AngII to constrict renal resistance vessels. We used A1‐knockout (A1−/−) and wild‐type (A1+/+) mice to investigate the synergism between AngII and low‐dose Ado in regulation of arteriolar responses.METHODSContractions were measured in renal afferent arterioles from nontreated mice and those with 14‐days pretreatment with L‐NAME (10‐4M) or AngII (400 ng/kg/min). Concentration response curves were obtained by Ado (10‐8M; 15 min) alone, or in combination with cumulative application of AngII (10–12 to 10‐6M).RESULTSAdo contracted arterioles from A1+/+ (11%), but had no significant effect in A1−/−. Ado significantly enhanced AngII‐mediated contraction in both genotypes, however, the contractile response was stronger in A1+/+ (56%) than in A1−/− (40%). Prolonged treatment with L‐NAME or AngII did not change the responses to Ado alone. However, arteriolar response to combination with Ado+AngII was enhanced in A1+/+, but was attenuated in A1−/−.CONCLUSIONLow‐dose Ado augments AngII‐induced constriction in both A1+/+ and A1−/−, by non‐receptor‐mediated actions. Underlying mechanisms may involve modulation of NO bioavailability or intracellular effects of Ado, introduced by Ado‐transporters.
Structural determination of OATP transporters utilising homology models and cell based assays
Authors: Taylor-Wells Jennina C. , Meredith David , Kelly Sarah 
Published: June 2021

Membrane transport proteins (transporters) are present in the lipid bilayer of cells and selectively transport compounds across the membrane. The organic anion transporting polypeptides (OATPs) are a family of membrane transporters expressed in a variety of tissues, including absorptive/excretory cells of the liver, kidney and intestine. In addition, OATPs transport an array of endogenous and xenobiotic compounds including bile salts, thyroid hormones, statins and antineoplastics. OATPs play an important role in cell homeostasis and drug absorption/excretion, and have also been implicated in disease and drug‐drug interactions. However there is still much to determine regarding the binding properties and exact structure of these proteins. The topology and binding properties of OATP1A2, OATP1B1, OATP1B3 and OATP2B1 have been investigated using a HEK293T cell model.OATP proteins have been expressed in HEK293T cells and kinetic properties determined using the OATP substrate estrone‐3‐sulfate. Bioinformatics analysis using various topology models has revealed that OATP1B1, OATP1B3 and OATP2B1 have between 11–12 transmembrane domains. However there could be as few as 8 domains, as is the predicted topology of the less well characterised OATP1A2. The topology of these proteins has been experimentally investigated using a FLAG epitope tag recognition system. Epitope tags were cloned into the putative extracellular regions of the protein, which were recognised by a FLAG antibody. The detection of the antibody was quantified by a chemiluminescence method and those detected confirmed as extracellular regions. The findings of this study will be used to further determine drug transport pathways and aid in future drug development.
Antenatal nicotine exposure results in programming of aberrant alveolar development and interstitial pulmonary fibrosis in adult male rats
Authors: DASGUPTA CHIRANJIB , Xiao DaLiao , Xu Zhice , Yang Shumei , Zhang Lubo 
Published: June 2021

ObjectiveIdentification of abnormalities in lung structure, and expression of profibrotic proteins in the adult rat offspring lung exposed to maternal smoking in fetal life.MethodsAntenatal nicotine exposed adult offspring lungs were analyzed for lung volume (LV), lung/body weight ratio (L/BWR), morphology, and protein expression patterns.ResultsMale offspring lung showed decreased radial alveolar count, thickened alveolar septa, with heightened interstitial collagen expression, angiotensin II type 1 receptor (AT1R), TGF‐ β1, and CTGF proteins. In contrast, female offspring lungs had reduced L/BWR, increased LV, and expression of angiotensin II type 2 receptor (AT2R), resulting in the decreased AT1R to AT2R ratio. Smad3 expression was down‐regulated in male but not in female lungs.ConclusionsAntenatal nicotine exposure results in fetal programming of abnormal lung development linking maternal nicotine use to increased susceptibility of interstitial pulmonary fibrosis in adult male offspring lung in a sex‐dependent manner.Supported in part by NIH grant HL83966
Proliferation of human alveolar epithelial cells down‐regulates ACE‐2 activity
Authors: Dang Vinh Xuan , Uhal Bruce David 
Published: June 2021

In pulmonary fibrosis, a profibrotic effect is mediated by angiotensin II (ANGII). The accumulation of ANGII is limited by its conversion to angiotensin 1‐7 (ANG1‐7) by angiotensin converting enzyme‐2 (ACE‐2). Previous work from this lab demonstrated that ACE‐2 is protective against fibrogenesis, but down‐regulated in human and experimental lung fibrosis. ACE‐2 is expressed primarily by alveolar epithelial cells (AECs), which are quiescent in normal lung but proliferate in lung fibrosis. On this basis, we hypothesized that ACE‐2 activity would be dependent on cell cycle progression. It was predicted that ACE‐2 activity would be greater in quiescent cultures of human AECs (A‐549) compared to their proliferating counterparts. ACE‐2 activity was measured by assay with an ACE‐2 fluorogenic substrate and normalized to protein concentration. A competitive inhibitor for ACE‐2, Dx600, was co‐administered to analyze the specificity. In A‐549s, ACE‐2 activity was five‐fold greater in quiescent cells than proliferating cells (p = 0.0008). Inhibition of ACE‐2 with Dx600 demonstrated high specificity of the fluorogenic substrate. A similar effect was also seen in mouse lung epithelial cells (MLE‐12) with similar statistical significance (p < 0.001). These data show that proliferation of AECs down‐regulates ACE‐2 activity as a normal but unfortunate consequence of AEC proliferation during fibrogenesis. This cell culture model can be used to investigate the molecular control of the down‐regulation.Support: PHS HL‐45136
Angiotensin type 1A receptors (AT1a) and reactive oxygen species (ROS) mediate nuclear factor‐κ‐B (NF‐κB) activation in the subfornical organ (SFO) during slow‐pressor Angiotensin‐II (Ang‐II) hypertension
Authors: Li Anfei , Young Colin N. , Davisson Robin L. 
Published: June 2021

We recently showed that NF‐κB is activated in the SFO of the brain during slow‐pressor Ang‐II hypertension (HTN). The molecular mechanisms contributing to NF‐κB activation, however, remain unclear. We tested the hypothesis that NF‐κB activation in the SFO during slow‐pressor Ang‐II HTN is mediated by AT1a receptors and ROS. Male AT1a flox mice underwent SFO‐targeted injections of an adenovirus encoding firefly luciferase downstream of NF‐κB response elements, in conjunction with adenoviral delivery of Cre‐recombinase (Cre) for selective deletion of AT1a or control LacZ. After recovery, osmominipumps were implanted for slow‐pressor Ang‐II infusion (600ng/kg/min), and NF‐κB activity in the SFO was measured daily using in vivo bioluminescence imaging. A surge in SFO‐NF‐κB activity was seen at day 5 of slow‐pressor Ang‐II infusion and this was significantly reduced by deletion of AT1a (LacZ 1.8 ± 0.7 vs Cre −0.2 ± 0.1 photons/s fold baseline, p<0.05, n=6). In a separate cohort of mice, scavenging of superoxide in the SFO via adenoviral overexpression of CuZnSOD also prevented the prehypertensive surge in NF‐κB activity (Day 5: LacZ 1.5 ± 0.7 vs CuZnSOD −0.5 ± 0.1 photons/s fold baseline, p<0.05, n=9–10). These findings suggest that AT1a redox‐sensitive mechanisms are key steps mediating SFO‐NF‐κB activation during slow‐pressor Ang‐IIHTN. HL864624