bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of MetaboAnalyst as a tool to study metabolomics data for a dietary intervention study
Authors: Panjeton Geoffrey D. , Remz Matthew A. , Allen Hannah J. , Powell David H. , Borum Peggy R. 
Published: June 2021

BackgroundMetabolomics is the comprehensive analysis of metabolites (<1500 Da). MetaboAnalyst (MA) is web‐based, publicly available software for analysis of quantitative metabolomics data.ObjectiveTo demonstrate the use of MA in a pilot study evaluating the effect of diet change on the human plasma metabolome.MethodsPlasma collected from healthy adult females before and after 5 days of receiving a high‐fat, low‐carbohydrate, and adequate protein diet were analyzed using HPLC‐ESI‐TOF‐MS. Features (mass/retention time) and abundances were uploaded to MA for analysis. PCA and PLS‐DA were used to differentiate between groups. Features were selected based on significance, using a volcano plot (p of 0.1 and fold change of 2). The remaining features were filtered based on presence in samples. A heatmap was used to identify clusters of features.ResultsThe volcano plot showed that less than 5% of the features were significant. The number of features was reduced from 2225 to 81 and 48 of these features were present in 50% of the subjects. Using these targeted 48 features, the PCA, PLS‐DA, and heatmap showed improved clustering of subjects based on diet group compared to the global analysis.ConclusionsMA can be used to evaluate the effects of a diet change on the plasma metabolome.Supported in part by the National Institutes of Health (NIH) and National Center for Research Resources (NCRR) CTSA grant 1UL 1RR029890.
Increasing the number of masticatory cycles reduces food intake in healthy young adults
Authors: ZHU YONG , HOLLIS JAMES H 
Published: June 2021

To investigate if the number of masticatory cycles made during ingestion affects satiation, 47 healthy participants (16 lean, 16 overweight and 15 obese) were recruited for this present study. Pizza rolls were used as the test food and their habitual mastication parameters were measured before they were randomized to a treatment order. Participants were asked to consume the same breakfast and reported to the laboratory for lunch, once a week for three weeks. After baseline appetite measures were made they were asked to eat until they were comfortably full, by chewing each portion of the food at their habitual number of chews, 150% or 200% of their habitual number of chews. Subjective appetite was measured regularly for 60 minutes and upon meal termination. There was no effect of body mass index (BMI) on habitual number of chews, chewing rate and chewing duration. Adjusting for BMI, increased number of masticatory cycles resulted in increased meal duration (P<0.0001) and reduced food intake (P=0.0026). 200% of the habitual number of chews reduced the food intake by 15% (P=0.0007) whereas 150% of the habitual number of chews reduced the food intake by 10% (P=0.0257). The number of chews did not affect hunger, fullness, desire to eat and palatability of the test food. The results suggest increasing the number of chews promotes satiation and could be a strategy for body weight management.Grant Funding Source : Iowa State University
Role of clathrin‐mediated endocytosis in transferrin‐bound iron uptake by hepatocytes
Authors: Zhang Lin , Knutson Mitchell 
Published: June 2021

After erythroid cells of the bone marrow, hepatocytes of the liver represent the second largest consumer of transferrin‐bound iron, accounting for 10–20% of iron exchange with the plasma. Although it is well known that transferrin is taken up by cells via endocytosis, a previous study in hepatocytes found that chemical inhibitors of endocytosis did not inhibit the assimilation of iron from transferrin. The aim of the present study was to investigate the role of clathrin‐mediated endocytosis in the uptake of transferrin‐bound iron by HepG2 cells, a human hepatoma cell line. We used siRNA to suppress the expression of clathrin and then incubated the cells with 59Fe‐labeled transferrin for 1 hour. Although suppression of clathrin resulted in a 70% lower uptake of transferrin, the cellular assimilation of 59Fe iron was unaffected. These data suggest that HepG2 cells take up transferrin primarily through clathrin‐mediated endocytosis, but that endocytosis is not required for the uptake of iron from transferrin. Funded by NIH.Grant Funding Source : NIH
Role of the iron‐import protein DMT1 (Divalent Metal Transporter 1) in liver iron uptake
Authors: Wang Chia-Yu , Knutson Mitchell 
Published: June 2021

DMT1 is required for intestinal iron absorption and the uptake of iron by developing erythroid cells. Here we used hepatocyte‐specific DMT1 knockout mice (Dmt1liv/liv) to examine the role of DMT1 in the liver. Dmt1liv/liv mice were crossed with models of genetic iron overload, i.e., Hfe−/− and hypotransferrinemic (Hpx) mice, to determine the role of DMT1 in hepatic iron accumulation. We found that Dmt1liv/liv mice had normal hepatic non‐heme iron concentrations and that the double‐mutant Dmt1liv/liv:Hfe−/− and Dmt1liv/liv:Hpx mice accumulated similar amounts of hepatic iron as did their respective Hfe−/− and Hpx controls. To determine if hepatocyte DMT1 is required for the uptake of non‐transferrrin‐bound iron (NTBI) and the assimilation of iron from transferrin, we injected 59Fe‐labeled NTBI or transferrin into Dmt1liv/liv mice and measured hepatic 59Fe uptake. We found that Dmt1liv/liv mice efficiently took up NTBI, but had a 40% reduction in the assimilation of iron from transferrin. These data indicate that DMT1 is not required for hepatic iron accumulation under normal and iron overload conditions, but it is required for the efficient assimilation of iron from transferrin. Funded by NIH.Grant Funding Source: NIH
Posttranslational Regulation of the Menkes Copper ATPase (Atp7a) in Intestinal Epithelial Cells
Authors: Xie Liwei , Collins James F. 
Published: June 2021

Atp7a pumps copper into the trans‐Golgi for cuproenzyme synthesis and also functions to export copper from enterocytes. It was noted that copper treatment of rat intestinal epithelial (IEC‐6) cells increased Atp7a protein abundance without effecting mRNA levels. We thus hypothesized that intracellular copper stabilizes the Atp7a protein and studies were designed to test this possibility. Differentiated IEC‐6 cells were treated with a protein translation inhibitor (cyclohexamide [CHX]) at different concentrations for different times to estimate Atp7a protein half‐life. CHX at 10 μg/ml for 48 hours led to >50% reduction in immunoreactive Atp7a protein. Next, IEC‐6 cells were exposed to 10 μg/ml CHX in the presence or absence of added copper (150 μM) for 48 hours and Atp7a protein abundance was determined. Results showed that copper stabilized the Atp7a protein, as protein abundance in CHX/Cu treated cells was similar to control cells treated with vehicle while CHX alone led to >50% protein reduction. To determine the mechanism, further studies will be designed to assess the role of the 6 metal binding domains of Atp7a, as not all of them are required for Atp7a copper transport function. We conclude that Atp7a is stabilized by copper, which could be particularly relevant during iron deficiency when the copper content of the intestinal mucosa increases and Atp7a protein abundance in enterocytes increases dramatically.Grant Funding Source : 1R01 DK074867
Development and validation of a urinary biomarker for dietary furanocoumarins
Authors: Simpkins Scott William , Young Lindsay Rae , Peterson Sabrina 
Published: June 2021

Furanocoumarins from food sources (e.g., parsnip, parsley, citrus) have been shown to inhibit carcinogen‐activating cytochrome P450 enzymes and may therefore play a role in prevention of cancer. Development of a biomarker to assess exposure to dietary furanocoumarins could be an alternative to recall‐based dietary assessment methods and be useful for epidemiologic studies of diet and cancer.In a combined dose‐response and pharmacokinetics study, timed urine samples were collected from 10 men and women over 168 hours following low (2g/kg body weight) and high (4g/kg body weight) doses of furanocoumarin‐containing vegetables (parsnips and parsley). These samples were analyzed to confirm 8‐ methoxypsoralen (8‐MOP) and 5‐methoxypsoralen (5‐MOP) as suitable biomarkers of dietary furanocoumarin intake. Pooled control urine, obtained from subjects following a week‐long abstention from furanocoumarin‐containing foods, was utilized for method development.Following β‐glucuronidase/sulfatase hydrolysis, urine samples were processed via solid phase extraction and analyzed by liquid chromatography‐mass spectrometry. Recoveries of 8‐MOP and 5‐ MOP were > 80%. Intraday coefficients of variation were < 4% for both analytes with estimated detection limits of 6.0 pM (1.3 pg/mL). With analysis times under five minutes, this method is rapid and robust enough for application to future epidemiological studies.
Fatty acid composition of erythrocytes reflects CLA intake in a depletion‐repletion study with healthy subjects
Authors: Nunes Juliana Côrtes , Penedo Letícia Abel , Torres Alexandre Guedes 
Published: June 2021

We studied fatty acid (FA) composition of erythrocytes in response to CLA depletion (8 w) and CLA repletion (8 w), in 27 men and women, aged 23 to 36 years. During the depletion phase all participants excluded sources of dairy fat from their diets and in the repletion phase they returned to their habitual diets and received 20 g of CLA‐biofortified butter, resulting in the intake of 1 g CLA/d. The FA composition of erythrocytes was determined by GC after lipid extraction and FA transesterification. Twenty‐seven FA were detected in the erythrocytes. The CLA contents (g/100g FA) in erythrocytes decreased significantly (p<0.01) in the depletion phase (0.18±0.03) when compared to baseline (0.31±0.05) and increased in the repletion phase (0.34±0.06). In addition, the CLA contents in erythrocytes were positively correlated with the habitual intake of CLA food sources obtained from a food‐frequency questionnaire. The ratio between 20:4n‐6 and 20:3 n‐6 was used as indicator of Δ5‐desaturase activity and reduced (p<0.05) in the CLA repletion phase. In addition, arachidonic acid was negatively correlated (r= 0.49; p<0.05) with CLA in erythrocytes. Our results are suggestive of erythrocyte composition as marker of CLA intake and of effects of CLA on Δ5‐desaturase activity, which could mediate some of the observed biological effects of CLA.Grant Funding Source: FAPERJ, CAPES, CNPq (Brazil).
The effects of almonds on the profile and bioaccessibility of isoflavones (IFN) from a soy soft pretzel
Authors: Simmons Amber L , Chitchumroonchokchai Chureeporn , Failla Mark L , Vodovotz Yael 
Published: June 2021

Soy IFN have many purported health benefits including reducing the risk of hormone‐related cancers. β‐glucosidase activity is inherently present in almonds and converts IFN to aglycones, a potentially more bioaccessible form. To test the effects of β‐glucosidase on the bioaccessibility of IFN, a soy soft pretzel was developed as a model snack food delivery system with and without almond. Also, the lipid component was altered to assess matrix effects. Each pretzel was homogenized and subjected to a 3‐stage in vitro digestion model. IFN that partitioned in the aqueous fraction of chyme were considered bioaccessible. Each pretzel contained 95.7±8.2 μmol of total IFN. Almond added at 5.8 and 12% increased the proportion of IFN aglycones by 8.8±2.4% and 23.3±3.9%, respectively, compared to the control (2.9 shortening, p<0.05). An average of 85.2±8.0% of IFN in the starting material was recovered in the aqueous fraction regardless of the type or amount of lipid. In conclusion, almond promoted partial conversion of IFN to aglycones without affecting bioaccessibility. This implies that the health promoting potential of snack foods containing soy may be enhanced when fortified with almond.Grant Funding Source : Ohio Agricultural Research and Development Center
Serum inosine, and symmetrical di‐methyl arginine (SDMA) concentrations were reduced at different time points when dogs were fed a controlled protein and phosphorus food with different fatty acid compositions
Authors: Jewell Dennis Edward , Yerramilli Maha , Obare Edward , Yerramilli Murthy 
Published: June 2021

Dogs (43, 3.1 to 14.8 years of age) were assigned to one of three dietary treatment foods which was fed throughout the experiment in order to evaluate the effect of food on specific circulating metabolites. Dogs were analyzed for body composition and serum analyzed at 0, 1, 3 and 6 months. Serum analysis included urea, albumin, fatty acids, inosine and SDMA. The experimental protocol was reviewed and approved by the Institutional Animal Care and Use Committee. All foods contained approximately 14% protein and 18% fat. Fatty acid composition was as follows:

Food
12:0
18:2  n6
18:3  n3
20:5  n3
22:6  n3

Control (C)
0.01
3.07
1.27
0.01
0.0

C + fish oil (CFO)
0.01
3.09
1.35
0.10
0.07

CFO + coconut oil (CFOCO)
0.87
4.61
1.63
0.23
0.17

Serum fatty acid concentration increased in response to increased intake throughout the study. There was no change in albumin concentration or lean body mass. There was a decrease in serum urea nitrogen and inosine after one month and through the rest of the study (P<0.05). There was no change in SDMA at one month but a significant decrease (P<0.05) through the rest of the study. The finding that SDMA was not different at one month while urea, inosine and the fatty acids mentioned above were all changed suggests that SDMA was controlled through a different function, reflecting an adaption to the dietary intake rather than a mass action response.This research was supported by Hill's Pet Nutrition and IDEXX Laboratories.
Sustainability of Backyard Gardening to Improve Nutrition in HIV‐affected Individuals in Swaziland
Authors: Malinga Steven , Magagula Celinhlanhla , Sibiya Thulani , Benson Shelby , Ramlal Roshan T 
Published: June 2021

ObjectiveThe CDC‐funded Community Linkages Project aims to improve nutrition of HIV‐affected individuals through backyard gardening in Swaziland.MethodsQuantitative and qualitative data collected from February 2010 to September 2011 were used to assess the sustainability of backyard gardening to improve nutrition among those affected by HIV. Individuals included those at high risk of malnutrition due to comorbidities such as HIV and tuberculosis. The project provided training, garden tools, seeds of six vegetables and ongoing supervision to 355 individuals establishing backyard gardens. Individuals from dry and humid climates, across 14 clinics, who did not own a garden and were willing to participate, were selected and monitored. Individuals were categorized according to garden progress as follows, stage 1: land clearing and preparation, stage 2: seedbed preparation and transplanting, stage 3: weeding, watering, pest and disease control, and stage 4: harvesting.Results191 individuals were evaluated; others being lost to death or relocation. Of 191, 85% sustained their garden after a year (stage 3 or 4). Interviews showed benefits included many teaching neighbors the practice and expanding gardens to larger areas.ConclusionIn a country where food and micronutrient supplements are becoming less popular due to issues of sustainability and cost, backyard gardens are a viable alternative.
Phosphorylation of cytokeratin fibers alters their response to mechanical extension
Authors: Fois Giorgio , Weimer Michael , Felder Erika T , Zheng Xing , Tobias Busch , Seufferlein Thomas , Dietl Paul , Felder Edward 
Published: June 2021

Cytokeratin (CK) fibers protect epithelia from mechanical stress. High loads of mechanical strain lead to overextension of the CK‐fibers, discernible by wavy CK‐fibers in living cells after the strain is released. As mechanical properties of CK‐fibers are modulated by phosphorylation, we investigated the effect of phosphorylation on the waviness of overextended CK‐fibers.Using FP‐labeled CK8/18 constructs and a cell stretching device, we found that wavy CK‐fibers were prevented by treatment with Staurosporin (unspecific kinase inhibitor), by depleting the cells of ATP and with CK‐mutants that abrogate phosphorylation at specific sites. Interfering with actin/myosin had a similar effect. The time that it took the CK‐fibers to regain their taut structure was not affected by phosphorylation but clearly depended on intact microtubuli.Further experiments will identify the signaling pathway for CK‐fiber dephosphorylation and will demonstrate if the mechanical stimulation itself triggers this pathway ‐ possibly as an adaptive mechanism to protect the CK‐fibers from mechanical damage.This work was supported by the DFG, grant DI 1402/1‐1 and DI1402/3‐1, and the Baden‐Württemberg Stiftung, grant P‐LS‐Biomat/03.
Newly Designed and Improved Human Soluble Epoxide Hydrolase Inhibitors for Neuropathic pain
Authors: Lee Kin Sing Stephen , Liu Jun-Yan , Inceoglu Bora , Wagner Karen , Dong Hua , Rose Tristan E. , Yang Jun , Morisseau Christophe , Hammock Bruce D. 
Published: June 2021

Soluble epoxide hydrolase (sEH, EC 3.3.2.10) is responsible for metabolism of endogeneously derived fatty acid oxiranes, epoxyeicosatrienoic acids (EETs) to the corresponding diols, dihydroxyepoxyeicosatrienoic acids (DHETs). EETs are the products of arachidonic acid by cytochromes P450 epoxygenases and are key modulators involved in inflammation, pain and blood pressure. Inhibition of sEH that results in an increase in endogenous EETs, which have a significant effect on resolving inflammation and high blood pressure in rodent models. Therefore, the sEH has emerged as a pharmaceutical target for hypertension, inflammation and organ‐protection. Recently, we have demonstrated that elevation of epoxy‐fatty acid through sEH inhibition is able to resolve diabetic neuropathic pain in rodent.Over last decade, a series of N,N′‐disubstituted ureas has been developed to study the physiological effects of sEH inhibition in various murine and rodent models and their beneficial effects in several animals disease models has been demonstrated. To better study the effect of epoxy‐fatty acids on health, a set of new compounds with dramatically potency, a better solubility and an improved pharmacokinetic profiles has been synthesized, their PK‐ADME and efficacy on diabetic neuropathic pain will be determined and the results will be presented and discussed here.
Role of Beta2‐Adrenoceptor Signaling and Mitogen Activated Protein Kinases in IL‐13 Induced Mucus Production in Human Airway Epithelial Cells
Authors: Al-Sawalha Nour , Pokkunuri Indira , Omoluabi Ozozoma , Bond Richard , Knoll Brian 
Published: June 2021

Excessive airway mucus production by airway epithelium is a hallmark feature of asthma that contributes to airway obstruction. Our objectives were to determine the requirements for β2‐adrenoceptor (β2AR) signaling and mitogen activated protein kinases (MAPKs) in enhancing the expression of MUC5AC, which encodes a major airway mucin, in response to IL‐13 in normal human bronchial epithelial cells (NHBECs). Cells were cultured at air‐liquid interface for 14 days on Transwell filter supports and MUC5AC expression was assessed by quantitative RT‐PCR. Only in the presence of epinephrine (3 μM) was MUC5AC transcription induced in response to IL‐13 (20 ng/ml); there was a 14.9‐fold increase in MUC5AC transcript numbers in cells cultured with IL‐13 and epinephrine compared to epinephrine alone. The addition of ICI‐118,551, a selective β2AR inverse agonist, blocked MUC5AC expression while CGP‐20712A, which is a β1AR selective antagonist, did not. MUC5AC expression in response to IL‐13 and epinephrine was blocked by treatment with chemical inhibitors of MEK‐1/2, ERK‐1/2, JNK or p38. We conclude that β2AR signaling is required to induce MUC5AC expression in response to IL‐13. Moreover, MAPKs are components of the required β2AR/IL‐13 receptor signaling pathways in producing MUC5AC expression in human airway epithelial cells.Supported by NIH 1R01A179236 to RAB
Thyroid hormone affects both endothelial and vascular smooth muscle cells in rat arteries
Authors: Cai Yin , Leung George P.H. , Vanhoutte Paul M. 
Published: June 2021

SAR, China, Peopleˈs Republic of The effect of thyroid hormone on vascular cells is controversial. The present study investigated in isolated arteries [with and without endothelium; suspended for isometric tension measurement] whether or not thyroid hormone causes relaxations in, or alleviates endothelial dysfunction in diabetic animals.Triiodothyronine, (T3) did not relax aortae of control rats with or without endothelium but caused endothelium‐independent decreases in tension in mesenteric arteries, suggesting an endothelium‐independent vasodilator effect of the hormone.In femoral arteries of rats with streptozotocin‐induced Type 1 diabetes, A23187 caused the release of endothelium‐derived contracting factors (EDCF). After four weeks of chronic treatment with T3, the contractions to A23187 of preparations with endothelium were unchanged, but those without endothelium were augmented, suggesting that the release of EDCF was reduced. Thus, thyroid hormone affects both endothelial and vascular smooth muscle cells in rat arteries.
Increased Lymphatic Permeability During Shock and Burn Trauma Alters Antigen Presenting Cell Recruitment to Mesenteric Lymph Vessels
Authors: Cromer Walter Emerson , Zawieja Scott , Stagg Hayden , Hunter Felicia , Tharakan Binu , Meininger Cynthia , Childs Ed , Zawieja David 
Published: June 2021

Recent attempts to define mediators of lymphatic permeability and their functional roles have been made but few definitive conclusions have been drawn. We hypothesize that failure of the lymphatic barrier induced by inflammatory cytokines during trauma leads to enhanced trafficking of antigen presenting cells to the lymphatic in the mesentery.Lymphatic endothelial cell (LEC) permeability was measured using a transwell FITC‐BSA assay. LECs were treated with inflammatory cytokines or serum from rats subjected to either hypovolemic shock (HVS) or burn trauma (BT). Also, mesenteric tissues were harvested from sham, HVS and BT and stained for MHCII expression.LEC permeability increased when treated with HVS, or BT serum or inflammatory cytokines (in particular IL‐6, which produced responses similar to HVS & BT). Numbers of MHCII cells associated with mesenteric lymphatics increased with both HVS and BT as expected.We examined the effect of mediators of LEC permeability and what effects this might have on immune cell trafficking. We conclude that LECs can alter their barrier in response to mediators of permeability and that the number of MHCII cells increases around lymphatics under conditions of increased permeability. Together these findings present a new role for lymphatics in both immunology and physiology.