bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Profiling Reveals Differences in Plasma Concentrations of Arabinose and Xylose after Consumption of Fiber‐rich Pasta and Wheat Bread with a Differential Rate of Systemic Appearance of Starch‐derived Glucose in Healthy Men
Authors: pantophlet andre , eelderink coby , vonk roel , wopereis suzan , dijk‐stroeve annelies , bijlsma sabina , van stee leo , bobeldijk ivana , priebe marion 
Published: November 2023

Consumption of starchy products with slowly digestible starch is implicated with a lower risk of metabolic diseases. Previously, it has been shown that pasta consumption resulted in a lower rate of appearance of exogenous glucose (RaE) and lower glucose clearance rate quantified with a dual isotope technique, which was in accordance with a lower insulin and GIP response after pasta intake. To get more insight in the acute metabolic consequences of the intake of products with differential rate of appearance of starch‐derived glucose, plasma metabolic profiles in 9 healthy men were analyzed after consumption of wheat bread and pasta, both enriched with wheat‐bran.Differences in postprandial responses of 134 plasma metabolites were analyzed using a GC‐MS ‐based metabolomic approach. Six samples were analyzed per subject; one baseline sample and 30, 60, 90, 120 and 180 min after consumption. A two‐way ANOVA was used to analyze the effect of time, treatment, and their interaction. Additionally, pathway analysis was performed.The observed differences occurred primarily in pathways related to protein and energy metabolism. Profiles of various amino acids had similar postprandial patterns and showed lower and attenuated responses after pasta, which could be explained by a slower absorption (parallel to the lower RaE) as well as the lower insulin response after pasta. Metabolites of glucose metabolism showed similar profiles as RaE, whereas metabolites of lipid metabolism were suppressed for a longer time after pasta intake. Remarkable higher plasma concentrations of arabinose (A) and xylose (X) after consumption of pasta were found. A and X are derived from arabinoxylans (AX), which are important components of wheat bran. The higher bioavailability of A and X coincided with a lower rate of appearance of glucose and amino acids. This is possibly due to higher viscosity of AX in the small intestine after pasta consumption, which is hindering absorption. The lower rate of glucose appearance is thus apparently not caused by slow starch digestion, but by slow absorption of starch‐derived glucose. As both food products contained the same amount of AX, different methods of processing may explain the difference in viscosity. It is speculated that the higher bioavailability of A and X after pasta is due to higher degradation of AX by small intestinal microbiota, facilitated by higher viscosity of AX after pasta. These results suggest that also wheat bran, depending of processing, may increase viscosity of the meal bolus in the small intestine and interfere with macronutrient absorption, thereby influencing postprandial glucose and insulin response.Support or Funding InformationThe project was supported by UMCG, TNO, TIFN and ZON‐MW
Respiratory effects of weight loss or gain over 1 year in obese children
Authors: Bhammar Dharini M , Stickford Jonathon L , Kim Roy J , Marines‐Price Rubria , Bassett J. Todd , Roman Maria C , Kruetzer Andreas , Babb Tony G 
Published: November 2023

IntroductionThe purpose of this case series was to investigate the respiratory effects of weight loss or gain in obese children over 1 yr.MethodsTwo obese children filled out the physical activity questionnaire for children (PAQ‐C) and underwent pulmonary function testing, dual‐energy x‐ray absorptiometry, maximal exercise testing, and constant load cycling at 40W before and after either 1 yr of: 1) exercise training and weight loss, or 2) free‐living weight gain. The children were not provided with a supervised intervention for weight loss or gain.ResultsSubject 1 was a girl, age 11.8yr, who engaged in a program of diet and regular exercise. The child's PAQ‐C score increased from 1.71 to 3.40. Height increased from 147.4 to 152.1cm, weight increased from 57.6 to 58.1kg, and BMI decreased from the 96th percentile (z‐score = 1.84) to the 93rd percentile (z‐score = 1.52). The percent body fat decreased from 44.1 to 36.3%, fat mass decreased from 25.4 to 21.1kg, and lean body mass increased from 32.2 to 37.0kg. FEV1/FVC ratio increased from 85 to 89%, TLC increased from 96 to 102% of predicted, and FRC (% TLC) increased from 34 to 40%. VO2peak (% predicted based on ideal body weight) increased from 106 to 117%. During constant load exercise at 40W, ratings of perceived exertion (RPE) reduced from 12 to 8, and ratings of perceived breathlessness (RPB) did not change (2 to 2).Subject 2 was a boy, age 10.8yr, who continued to gain weight. PAQ‐C score reduced from 2.12 to 1.94. Height increased from 150.2 to 157.6cm and weight increased from 76.3 to 91.9kg. BMI stayed over the 99th percentile, and the BMI z‐score increased from 2.53 to 2.60. The percent body fat increased from 48.3 to 50.6%, and fat mass and lean body mass increased from 36.9 to 46.5kg and 39.4 to 45.4kg, respectively. FEV1/FVC ratio decreased from 90 to 81%, TLC decreased from 110 to 102% of predicted, and FRC (% TLC) decreased from 32 to 22%. VO2peak (% predicted based on ideal body weight) decreased from 103 to 101%. During constant load exercise at 40W, RPE reduced from 11 to 10 and RPB reduced from 4 to 2.DiscussionAn exercise training and weight loss program in children could substantially alter body composition and improve respiratory function and aerobic fitness, while a continued weight gain trajectory worsens body composition and could negatively impact respiratory function and aerobic fitness. Furthermore, body composition determination may be an important tool to help clinicians track progress of children undergoing lifestyle interventions during maturation in addition to measurements of BMI percentile or z‐score.Support or Funding InformationSupported by unrestricted grant funds from Dr. Pepper Snapple, King Foundation, and Texas Health Presbyterian Hospital Dallas.
Calcium‐binding Peptides Isolated from Casein Hydrolysates Enhances Intestinal Calcium Uptake
Authors: Miao Jianyin , Liu Guo , Luo Zhen , Xia Zumeng , Liu Fei , Chen Yunjiao , Dixon William , Xiao Hang , Cao Yong 
Published: November 2023

The aim of this study was to isolate calcium‐binding peptides from casein hydrolysates and to determine their effects on intestinal uptake of calcium in Caco‐2 cell monolayers. Five peptide fractions (P1 to P5) with calcium‐binding capacity were isolated from casein hydrolysates using HPLC. All five fractions promoted calcium uptake by Caco‐2 cell monolayers with fraction P5 showing the highest potency in enhancing calcium uptake. Within 1 hour of treatment, fraction P5 increased the calcium uptake by more than 7‐fold compared to the control group. The chemical composition of P5 was elucidated using LC‐MS/MS analysis and the amino acid sequence was determined to be RELEELNVPGEIVESpLSpSpSpEESITR. This calcium‐binding peptide was derived from β‐casein and contained four characteristic phosphorylated seryl residues. Our results demonstrated that synthetic P5 also displayed capacity to increase calcium uptake in Caco‐2 cell monolayers. Overall, our results provide novel insight into the identity and potency of bioactive phosphopeptides from casein hydrolysates that may enhance intestinal calcium uptake.Support or Funding InformationTheauthors would like to express their gratitude to the Infinitus(China) Company Ltd for the financial support.
Testing the Use of Urinary Biomarkers to Assess Added Sugar Intake in Obese Postmenopausal Women
Authors: Arnold Kristen , Bomser Joshua , Andridge Rebecca , Orchard Tonya 
Published: November 2023

RationaleAssessment of dietary intake is most frequently done by self‐reported measures such as 24‐hour recalls and food frequency questionnaires. Although these measures are useful, there is error associated with self‐report. This is found to be particularly true in overweight/obese individuals and for specific foods perceived as having negative health outcomes (e.g. added sugars) which are often under‐reported. Therefore objective measurements are needed to more accurately assess dietary intake of certain nutrients. Urinary sucrose and fructose excretion measured in urine samples collected over 24 hours has been validated as a biomarker of added sugar intake in controlled feeding studies. However, whether a single spot urine sample can be used to assess self‐reported added sugar intake is less clear, especially in overweight/obese individuals.ObjectiveTest correlations between urinary biomarkers from a single spot urine sample and self‐reported dietary intake of added sugars in obese postmenopausal women.MethodsFasting urine samples were collected at the baseline visit from 8 postmenopausal women with a BMI >30, who were enrolled in a dietary intervention study aimed at lowering added sugars and increasing fiber and fatty fish. Urine samples were transferred to cryovials and frozen at −20 C until assayed in batches. Urinary sucrose and fructose excretion was measured using a modified enzymatic assay (Rosche BioPharm). Participants completed 24 hour recalls at the baseline visit with the guidance of a Registered Dietitian using the USDA 5‐step multiple‐pass method designed to enhance accuracy of dietary data collection. Self‐reported added sugar intake (g/d) was estimated using Nutritional Data System for Research (NDSR). Pearson correlations were used to examine associations of added sugar intake with urinary sucrose and fructose excretion.ResultsPreliminary baseline data from 24‐hour recalls revealed a mean added sugar intake of 40.1 g/d (SD 25.2), with a range of 0 – 97 g/d. Mean urinary sucrose excretion was 0.024 g/L (SD 0.004), range 0.000 – 0.108 g/L. Fructose in the urine was undetectable. A statistically significant correlation (r=0.74, p=0.04) was observed between baseline urinary sucrose excretion and added sugar intake from 24 hour recalls. There was no significant correlation (r= 0.15, p=0.81) between baseline urinary sucrose excretion and self‐reported sucrose intake, which includes sucrose naturally found in plant foods.ConclusionPreliminary cross‐sectional data from a small sample of postmenopausal obese females suggest that urinary sucrose excretion can be used as an objective biomarker of added sugar intake. This warrants further testing in a larger sample.Support or Funding InformationInternal Ohio State University Funds
iTRAQ‐Based Quantitative Proteomic Analysis of the Anticancer Mechanism of a Novel Ent‐kaurane Diterpenoid from RubuscorchorifoliusL.f
Authors: Chen Xuexiang , Gao Zili , Ou Yan Wen , Liu Guo , Gao Xiangyang , Liu Xiaojuan , Chen Yunjiao , He Lliping , Xiao Hang , Cao Yong 
Published: November 2023

Our previous study has identified (16R)‐16,17‐dihydroxy‐ent‐ kaur‐2‐one (a novel ent‐kaurane diterpenoid) from Rubuscorchorifolius L.f.as a potential anti‐cancer agent. Herein, we determined the mechanism of action of the diterpenoid in inhibiting the growth of human colon cancer cells. The results from flow cytometry analysis showed that the diterpenoid induced extensive apoptosis and cell cycle arrest in human colon cancer cells. iTRAQ‐Based Quantitative Proteomic analysis revealed that treatment with the diterpenoid led to upregulation of 67 proteins and down regulation of 53 proteins. These proteins play important roles in multiple cellular processes such as enzyme activity adjusting, electron transferring, anti‐oxidation and protein transcription. These proteins also are critical in path ways related to carcinogenesis such as oxidative phosphorylation pathway, cell cycle regulation, and p53 pathway. Treatment with the diterpenoid modulated the expression levels of APC, DCC, TGFβRII, Smad2m, Bax, p53 and 14‐3‐3σ, which may contribute to its inhibitory effects on colon cancer cells. Overall, our work produce dinitial mechanistic information on the action of (16R)‐16,17‐dihydroxy‐ent‐ kaur‐2‐one in inhibiting the growth of colon cancer cells, which provided important scientific basis for further investigation.Support or Funding InformationThe authors are grateful for the financial support from the University of International Cooperation in Science and Technology Innovation Platform Project of Guangdong (2013gjhz0003), the Joint Specialized Research Fund for the Doctoral Program of Higher Education (Grant No. 20114404120022),
Adenosine A2A Receptor Driven Impulsivity Promotes Cue‐Dependent Reward Seeking Behavior and Increases Hippocampal Immature Neurons
Authors: Oliveros Alfredo , Cho Chang Hoon , Choi Sun , Jang Mi‐Hyeon , Choi Doo‐Sup 
Published: November 2023

Mice lacking the ethanol‐sensitive equilibrative nucleoside adenosine transporter 1 (ENT1–/–) display enhanced goal‐directed behaviors due to decreased adenosine A2AR function. However, the role of A2AR signaling in the regulation of impulsivity remains unknown. Using Pavlovian conditioning, second‐order schedule discrimination, and the 5‐choice serial reaction time task (5‐CSRTT), which incorporates differential‐reward of low rate (DRL) schedules, we reveal that deficits in A2AR function promote impulsivity. ENT1–/– mice display exaggerated impulsive responses and faster reaction times to retrieve reward during conditioning and extinction. Interestingly, our results show that basal ERK1/2 phosphorylation is reduced in the dorsal hippocampus (dHPC) of ENT1–/– mice and that impulsive Pavlovian conditioning significantly increases ERK1/2 phosphorylation. Subsequently, we validate that inhibition of A2AR promotes impulsivity during Pavlovian conditioning and the 5‐CSRTT. In addition to increased ERK1/2 phosphorylation, mice demonstrating exaggerated impulsivity as a result of A2AR inhibition exhibit enhanced expression of doublecortin and increased incorporation of BrdU within the HPC. Taken together, these findings indicate that impaired ENT1/A2AR signaling promotes impulsivity during cue‐induced conditioning and contributes to reward seeking during extinction. More importantly, these results demonstrate that impulsive behavior is associated with aberrant hippocampal neurogenesis, which may contribute to the development of maladaptive reward‐seeking behaviors.Support or Funding InformationNIH R01 AA018779
Co‐ultra PEALut enhances neuronal recovery after a moderate traumatic brain injury
Authors: Campolo Michela , Crupi Rosalia , Cordaro Marika , Bruschetta Giuseppe , Siracusa Rosalba , Esposito Emanuela , Cuzzocrea Salvatore 
Published: November 2023

Traumatic brain injury (TBI) is a major health problem worldwide. Currently, there is no effective treatment to improve neural structural repair and functional recovery. Recently, has been demonstrated that hippocampal injury‐induced neurogenesis is one mechanism underlying endogenous repair following TBI. The aim of this study was to evaluate the neuro‐regenerative properties co‐ultra PEALut (constituted by the association of palmitoylethanolamide (PEA), with the flavonoid luteolin (Lut) in a mouse model of TBI until 7 days. TBI was induced in mice by the controlled cortical impact (CCI), one of the most common models of TBI; the mice were orally administered co‐ultra PEALut (1mg/Kg) 1h after trauma and daily for 72h and 7d. A conspicuously neurogenesis was seen in mice 72h and 7d after trauma. Co‐ultra PEALut treatment stimulated neuronal reconstitution process restoring the basal level of new neurons (by BrdU staining) and mature neurons (by doublecortin staining). Moreover this positive effect was associated with an important upregulation of neurotrophic factors (BDNF and NT‐3), ultimately leading to improvement in memory recall on behavioral testing (Morris water maze test).Co‐ultra PEALut could represent a therapeutic potential of augmenting the endogenous repair response for treating TBI.
In Vitro Characterization of a Novel Allosteric Potentiator of the Dopamine D1 Receptor
Authors: Heinz Beverly A , Schaus John M , Beck James P , Hao Junliang , Wang Xushan , Krushinski Joseph , Reinhard Matthew , Hellman Sarah , Getman Brian , Suter Todd , Nelson David , Wiernicki Todd , Cohen Michael P , Yang Charles R , Svensson Kjell A , Bruns Robert F 
Published: November 2023

Allosteric potentiators of the dopamine D1 receptor could be useful for treatment of Parkinson's disease, schizophrenia, depression, ADHD, and narcolepsy. We identified a novel D1 potentiator (“DETQ”)by high‐throughput screening followed by iterative chemical optimization. In a HEK293 cell line expressing the human D1 receptor, agonist‐stimulated cAMP production was measured in the presence of an EC20 concentration of dopamine using homogeneous time resolved fluorescence (HTRF) technology. DETQ potentiated the dopamine response with a mean EC50 of 5.8 nM and mean efficacy corresponding to 95% of the maximum response to dopamine. In the absence of exogenous dopamine (agonist mode), the maximum efficacy of DETQ was 11.6% with an EC50 of 30 nM; based on the initial slopes of the two curves (Ehlert R‐ratio), DETQ was thus 43‐fold less potent as an allosteric agonist than as a potentiator. When concentration‐response curves for dopamine were carried out at multiple DETQ concentrations in the cAMP assay, DETQ shifted the dopamine curve 21‐fold to the left with a KB of 26 nM. In experiments measuring binding of the D1 antagonist 3H‐SCH23390 to the human D1 receptor, 100 nM DETQ caused a 5‐fold leftward shift in the concentration‐inhibition curve for dopamine, indicating adirect effect of DETQ on the D1 receptor. The potency of DETQ in the cAMP assay was about 50‐fold lower at the mouse and rat D1 receptors than at human, rhesus, and dog D1 receptors. DETQ was inactive at concentrations up to atleast 10 uM when tested in agonist and potentiator modes at related receptors, including D2, D5, β1, β2, β3, and 5HT6. DETQ was also inactive in binding and/or functional assays at a largeset of unrelated targets.These results suggest that DETQ could be a useful tool to probe applications of dopamine D1 potentiators for CNS disorders.
GPCRs as Possible Therapeutic Targets in Pancreatic Cancer
Authors: Chang Sarah , McCann Thalia , Zhou Shu , French Randall , Lowy Andrew M , Corriden Ross , Insel Paul A 
Published: November 2023

Pancreatic ductal adenocarcinoma (PDAC, the most common type of pancreatic cancer) is the 4th leading cause of cancer deaths in the US and has a survival rate of ~5%. New therapeutic approaches are thus needed for this disease. PDAC tumors are composed of malignantductal epithelial cells, and cells of the tumor microenvironment, which includes inflammatory/immune cells, cancer‐associated fibroblasts (CAFs, stromal cells), vascular cells and dense extracellular matrix. In this study, we tested the hypothesis that PDAC cells express G‐protein‐coupled receptors (GPCRs, the largest class of targets of FDA‐approved drugs) that may be novel therapeutic targets for pancreatic cancer.We used GPCR Taqman arrays to identify and quantify mRNA of ~350 GPCRs and assessed PDAC tumors(n=3), patient‐derived PDAC cell lines (n =2), established PDAC cell lines (Miapaca, ASPC‐1), and patient‐derived pancreatic CAF cells (n=5). We found 77 GPCRs expressed commonly by the tumor samples, 46 GPCRs expressed in common in the patient‐derived and established PDAC cell lines and 104 GPCRs shared among the CAF samples.An orphan GPCR (termed Orphan A) was highly expressed in PDAC tumors and cells and CAFs, results confirmed by independent qPCR. OrphanA was among the most highly up‐regulated GPCRs in PDAC cells compared to their normal precursor, pancreatic ductal epithelial cells (HPDE6). Transfection of Orphan A into HPDE6 cells increased their DNA synthesis, implying that Orphan A enhances PDAC proliferation and that its inhibition may blunt tumor growth. These results indicate the utility of an unbiased Taqman array approach to identify GPCRs expressed by PDAC cells and pancreatic CAFs. We propose that GPCRs, such as Orphan A, whose expression is shared by these two cell types and more highly expressed than in normal precursor cells may be novel targets for the treatment of pancreatic cancer.Support or Funding InformationSupported by NIH R21CA189477 and T32CA121938
GPCRs as novel targets in pulmonary artery smooth muscle cells in pulmonary arterial hypertension
Authors: Sriram Krishna , Aroonsakool Nakon , Michkov Alexander V. , Insel Paul A. 
Published: November 2023

There is an unmet need for new therapeutics to treat pulmonary arterial hypertension (PAH): currently approved therapy has limited benefit in terms of overall mortality and many such treatments not only reduce vascular resistance in the pulmonary arterial tree but also have side‐effects, including systemic hypotension. We sought to determine if certain G‐protein‐coupled receptors (GPCRs) are more highly expressed in pulmonary artery smooth muscle cells (PASMCs) from patients with PAH compared to controls and thus might be novel therapeutic target for the treatment of PAH.METHODSWe performed GPCR expression profiling using qPCR‐based Taqman GPCR arrays that identify and quantify mRNA expression of non‐chemosensory endo‐GPCRs. Profiling was done on PASMCs isolated from PAH and non‐PAH patients. We also assessed GPCR expression in PASMCs from mice and rats and in SMCs from the human aorta and coronary artery.RESULTSPASMCs expressed ~120 GPCRs, including ~45 orphan (without known physiologic agonist) GPCRs. Numerous adhesion and frizzled receptors were detected: LPHN2, CD97, ELTD1 and GPR124 were among the highest expressed GPCRs in all human SMCs profiled. Expression and identities of the highest expressed GPCRs were consistent among biological replicates of non‐diseased human PASMCs. GPCR expression profiles were similar, between non‐IPAH PASMCs and SMCs from the aorta and coronary artery but PAH‐PASMCs showed changes in GPCR expression. We identified ~20 receptors with at least 2‐fold increases in expression in PASMCs from PAH patients compared to controls. These include numerous orphan receptors as well as GPCRs previously not known to play a role in PAH. In addition, a similar number of GPCRs had reduced expression in PAH‐PASMC relative to control‐PASMCs, indicating a subset of GPCRs that might be considered for gene‐based therapies of PAH. GPCR expression profiling in mouse and rat PASMCs revealed a high degree of similarity with PASMCs from human subjects, highlighting the utility of animal models and cells for further investigation of the physiological/functional role for the GPCRs we identified.CONCLUSIONNumerous orphan and previously under‐studied GPCRs are expressed by PASMCs with a number of GPCRs having increases/decreases in PAH compared to control PASMCs. GPCR expression in PASMCs from rats and mice are similar to that of human PASMCs, highlighting the potential for use of animal models to study these GPCRs as potential therapeutic targets for PAHSupport or Funding InformationSupported by DOD AWARD: No. W81XWH‐14‐1‐0372