bluuebunny/crossref_metadata_2025 huggingface dataset:
Reading and writing about science: Biochemistry, biomedicine and bioethics presented through the first year seminar
Authors: Rohlman Christopher
Published: June 2021

Presenting students with key questions where they explore their interest in biomolecular science early in their undergraduate careers provides a context for their further study. This is true for those wishing to pursue careers in STEM, but perhaps even more crucial for those who are not. These students need this context to be literate in the language and imagery of biochemistry and molecular biology in order to participate in the debates surrounding biomedicine, and make informed decisions. The challenge is how to present the required advanced concepts to students with little or no previous experience in a field that is traditionally taught in a multi‐year sequence. The first year seminar is a format that has long been used to allow students to consider interests in fields they might otherwise not, and develop critical thinking skills in the first semester of their undergraduate career. Over the past decade the first year seminar at Albion College has been used as a venue to introduce students to current biochemical research through critical discussion and writing. This format is adaptable to larger course structures as well. Non‐major students as well as future STEM majors have been participants in the courses. The seminars have recruited students to undergraduate and graduate study in biomolecular science, and introduced a larger number of non‐science students to the field.
Microbial composition and in vitro fermentation patterns of human milk oligosaccharides and prebiotics differ between formula‐fed and sow‐reared piglets
Authors: Li Min , Laura Bauer L , Chen Xin , Wang Mei , Kuhlenschmidt Theresa B , Kuhlenschmidt Mark S , Fahey George C , Donovan Sharon M
Published: June 2021

The effects of diet and age on in vitro fermentation of human milk oligosaccharides (HMO), lacto‐N‐neotetraose (LNnT), and three prebiotics (2:1 polydextrose / galactooligosaccharides and short‐chain fructooligosaccharides) by microbiota from the ascending colon of 9‐ and 17‐day‐old (do) formula‐fed (FF) and sow‐reared (SR) piglets were assessed. Short chain fatty acid (SCFA) concentrations were determined following 0, 2, 4, 8 and 12 h of incubation. LNnT fermentation produced more total SCFA, acetate and butyrate than the other substrates, whereas more propionate was produced from HMO. Total SCFA, acetate and propionate concentration were greater in FF and 9 do pigs, while SR produced more butyrate than FF. Microbiota was assessed by 16S rRNA gene V3 region denaturing gradient gel electrophoresis and realtime PCR. Microbial structures differed among the four groups before fermentation, with higher counts of Bifidobacterium in SR, and Clostridium cluster IV, XIVa and Bacteroides vulgatus in FF. Lactobacillus counts were higher in 9‐ than 17‐do pigs, regardless of diet. Bifidobacterium, Bacteroides, and clostridial species were increased after 8 and 12 h fermentation on most substrates. In summary, piglet diet and age affected gut microbiota composition and the fermentation patterns. HMO have potential prebiotic effects as evidenced by SCFA production and modulation of the microbiota (NIH R01 HD061929).

Grant Funding Source : NIH
Nutritional Assessment of Omani Patients with diabetes and Chronic Kidney Disease a case control study
Authors: Waly Mostafa , Ali Amanat , Al-Kalbani Shabib , Al-Maskari Masoud
Published: June 2021

Background

Chronic kidney disease (CKD) is a serious complication in patients with chronic uncontrolled type 2 diabetes mellitus (T2DM).

Objective

This study aimed to evaluate the nutritional status of T2DM patients undergoing hemodialysis.

Materials and Methods

A cross‐sectional study conducted in the main Renal Dialysis Center, Muscat, Oman. The subjects were 96 Omani adults undergoing hemodialysis (48 with T2DM and 48 with no T2DM diagnosis).

Results

The study subjects (62% male and 38% female) had a comparable mean age of 51± 8 years. As judged by body mass index, 86% of patients were underweight and 14% were average weight. Base line laboratory tests were comparable for all patients with the exception of fasting glucose and glycosylated hemoglobin (HbA1C) that were higher among T2DM patients. Nutritional status was assessed using the subjective global assessment score (SGA) that revealed that in T2DM patients 22% were severely malnourished, 25% were mild to moderately malnourished and 36% were normal as compared to the other group without T2DM (8% severely malnourished, 25% mild to moderately malnourished and 67% normal).

Conclusion

Nutritional status was well controlled in CKD patients without T2DM and it deteriorated in CKD patients with T2DM. It is suggested that an appropriate intervention program must be introduced to improve the nutritional status of CKD patients with T2DM.
Effects of Camellia‐Oil Enriched Diet on Oxidative Stress and Oxidized LDL‐C in Hypercholesterolemic Subjects
Authors: Bumrungpert Akkarach , Pavadhgul Patcharanee , Chusri Sirimano , Kalpravidh Ruchaneekorn
Published: June 2021

Camellia oil or tea seed oil is commonly used as an adjuvant in medicine. It is rich in mono‐unsaturated fatty acids (MUFA), vitamin E and phytochemicals. The objective of this study was to determine effects of camellia oil consumption on oxidative stress and LDL‐C oxidation in hypercholesterolemic subjects. The study design was a randomized, single‐blind controlled trial. Subjects with hypercholesterolemic were randomly divided into 2 groups.

The treatment group (n = 25) was provided camellia‐ oil enriched diet and the control group (n = 25) was provided diet cooked with soybean oil 3 meals/day for 8 weeks. Biomarkers of oxidative stress including glutathione (GSH) and malondialdehyde (MDA) and LDL‐C oxidation were assessed before and after intervention. Camellia oil consumption significantly decreased MDA (11.2%) whereas GSH was not changed compared with the control group. Moreover, camellia oil group demonstrated a statistically significant reduction of oxidized LDL‐C (8.7%) compared with the control group. In conclusion, these data indicate that the consumption of camellia‐ oil enriched diet could decrease oxidative stress and LDL‐C oxidation in hypercholesterolemic subjects. (Supported by Thailand Research Fund)
Relationship of cognitive function with plasma homocysteine, folate, vitamin B12 levels and nutrient intake in cognitively impaired elderly
Authors: Kim Ggotpin , Kim Hyesook , Kim Yoonsun , Kim Hee Jung , Son Jung In , Kim Seong Yoon , Chang Namsoo
Published: June 2021

This study investigated the relationship of cognitive function with plasma homocysteine (Hcy), folate, vitamin B12 levels and nutrient intake. A total of 321 subjects, including 121 normal subjects, 100 each from mild cognitive impairment (MCI) and Alzheimerˈs disease (AD) patients participated in this study (age 60 yrs and over). Diagnostic assessments were administered using the Korean version of Consortium to Establish a Registry for Alzheimerˈs Disease. Dietary intake was assessed using 24‐hour recall. Mean plasma Hcy level was higher in AD and MCI compared to normal subjects. AD group also had higher proportion of hyperhomocysteinemia and folate deficiency. Plasma Hcy level was negatively correlated with plasma folate and vitamin B12 levels, total intake of vitamin B2, vitamin B6, folate, vitamin B12, vitamin C and vitamin E. Multiple regression analysis with covariates revealed that plasma Hcy level was negatively, whereas plasma folate level, total intake of vitamin B2, vitamin B6, folate, vitamin C, vitamin E and beta‐carotene were positively associated with cognitive function. The results suggest that plasma Hcy, B vitamins and antioxidants intake are associated with cognitive function, and plasma Hcy level is negatively correlated with B vitaminsˈ nutritional status and antioxidants intake.

This work was supported by the Brain Korea 21 project.
Participation in the food stamp program, food insecurity and HIV‐disease among low income HIV+ adults in Miami
Authors: Hatsu Irene , Campa Adriana , Huffman Fatma , Johnson Paulette , Thomlison Barbara , Barr Shakira , Williams Shawn , Baum Marianna K
Published: June 2021

Objective

The objective of this pilot study is to define the relationship between participation in the food stamp program, food security and stage of disease in HIV+ adults.

Methods

Twenty one HIV+ patients were consented. Demographics, dietary intake and food security status were obtained using questionnaires. Disease stage and other health parameters were obtained from laboratory reports. Anthropometrics were taken. SPSS was used for analysis.

Results

The participants were mostly male (71%), African American (66.7%), had a high school education or lower (67%) and monthly income ≤$1,000 (66%). Although all were eligible, only about half (52%) received food stamps, and 57.1% (n=12) were food insecure. Of those receiving food stamps, 45.5% were food insecure compared to 70% of those not receiving food stamps. There was a significant positive correlation between participation in the food stamp program and feeling food secure (r=0.54, p<0.039) after controlling for age, gender, quality of life and lean body mass. Moreover, those who were food insecure had significantly lower CD4 count compared to food secure individuals (578 vs. 249 p<0.005).

Conclusion

Food insecurity is prevalent among HIV+ adults. Participation in the food stamp program significantly improves food security and is associated with slower HIV disease progression. A study with a larger sample size is needed to support these findings.
Sodium benzoate intake in beverages may contribute to ADHD symptoms in college students
Authors: Beezhold Bonnie , Johnston Carol S
Published: June 2021

Adolescents and young adults are the heaviest consumers of soft drinks in the U.S. population, consuming approximately 8% of their total daily energy intake from soft drinks. Recent research has demonstrated a link between sodium benzoate, a major preservative found in many soft drinks, juices, and coffee syrups, and attention deficit symptoms in children. Up to 8% of the American college population report clinically significant levels of ADHD symptoms. We surveyed 473 college students (125 males/326 females) about their intake of major sources of sodium benzoate over the last month, and assessed the presence of attention deficit symptoms using a brief validated ADHD screener. Prior to analysis, 22 participants with a psychiatric diagnosis or use of psychotropic therapy were removed. Sodium benzoate intake (SBI) was positively correlated with the ADHD screener score (n=451, r=.217, p=.000); controlling for age and BMI which were correlated with ADHD scores did not impact this relationship. Moreover, ADHD scores of students in the fourth quartile of SBI were significantly greater than for students in the first quartile (p=.002) and third quartile (p=.035) of intake. College students who consume a high quantity of soft drinks, coffee drinks and other major sources of sodium benzoate may be a vulnerable population for ADHD symptoms. This study was funded by the Nutrition Research Fund of the ASU Foundation.
Genetic variation in TAS1R2 taste receptor and sweet taste perception and sugar intake
Authors: Dias Andre Gautam , El-Sohemy Ahmed
Published: June 2021

Taste is one of the primary determinants of food intake and variation in genes affecting taste pathways may influence taste perception and food intake. The TAS1R2 protein is part of the putative TAS1R2/TAS1R3 sweet taste receptor and likely plays a primary role in detecting sugars. Our objective was to determine whether single nucleotide polymorphisms (SNPs) in the TAS1R2 gene affect sweet (sucrose) taste (n = 95) and intake of sugars (n=535). Sucrose taste thresholds were determined using a 3 alternative forced choice staircase model with solutions ranging from 9 ×10−6 to 0.5 mol/L. Genotypes for 23 SNPs in the TAS1R2 gene were extracted from an Affymetrix 6.0 chip. Sucrose and total sugar intake was calculated using a 196 item semi‐quantitative food frequency questionnaire. A general linear model was used to compute differences between genotypes. The rs12075191 (A>G) SNP was associated with sucrose taste and intake. Carriers of the A allele had lower taste thresholds (7.00 ± 1.65 vs 9.27 ± 0.63 mmol/L, p=0.058), lower total sugar intake (111.2 ± 7.3 vs 125.9 ± 2.4 grams, p = 0.05) and lower sucrose intake(41.1 ± 3.4 vs 48.7 ± 1.1 grams, p=0.03) than TT homozygotes. These results show that the rs12075191 SNP in the TAS1R2 gene modifies both sweet taste perception and sugar intake.

Grant Funding Source : The Advanced Food and Materials Network
Vegetarians have higher risk for inadequate intake of iron, zinc, and vitamin B12 compared to non‐vegetarians even when considering use of dietary supplements
Authors: Farmer Bonnie , Larson Brian , Keast Debra R , Fulgoni Victor L
Published: June 2021

Iron, zinc, and vitamin B12 have long been considered nutrients of concern for vegetarians, and vitamin D and calcium are of concern for both vegetarians (V) and non‐vegetarians (NV). Little data exist on the effect of supplementation on usual intakes of these nutrients, especially in V. Dietary intake from the National Health and Nutrition Examination Survey (2001 – 2008) was used to determine usual nutrient intake, with and without supplement use, for V and NV using the National Cancer Institute method. The percentage of each group having inadequate intakes (less than Estimated Average Requirements) was determined. Vegetarians were defined as those who did not report consuming meat, poultry, or fish on day one of the survey, representing a lacto‐ovo vegetarian dietary pattern. In subjects 19 years and greater (N=18,954), inadequacy for vitamin D and calcium was similar for V (n=1,138) and NV (n=17,816); over 65% of V and NV had inadequate intake of vitamin D, and over 35% had inadequate intake of calcium despite supplementation. Vegetarians had higher (p<0.01) prevalence of inadequate intake than NV for iron (16% vs 7%), zinc (51% vs 10%), and vitamin B12 (28% vs 2%) from food. When considering both food and supplements, inadequacy remained higher for V for iron, zinc, and vitamin B12 (12% vs 5%, 35% vs 7%, and 18% vs 1%, respectively). Although this reflects improvement with supplementation, iron, zinc, and vitamin B12 remain nutrients of concern for vegetarians.
Nutritional profiling of cod liver oil processed by molecular distillation, fermentation, or unrefined
Authors: Metzger Brandon T. , Barnes David M.
Published: June 2021

Eight commercial molecular distilled (MD), one commercial fermented, and five crude manufacturer supplied fish (Gadidae) liver oils were analyzed for fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), vitamin A and ester profiles, sterols, and oxidative state (malondialdehyde, MDA). Fatty acids and sterols were determined by GC‐MS, MDA by colorimetric assay, vitamin A by HPLC. Vitamin A ester profiles were determined by UPLC‐MS (QTOF). The ratio of DHA/EPA for MD products was 1.3–1.7 with one exception, while the fermented product (0.5), and crude samples (2.2–3.3) were different. The total concentration of EPA and DHA per 5 mL serving was 944–1200 mg in MD, 957 mg in fermented, and 182–274 mg in unrefined oil. MDA, an indicator of polyunsaturated fatty acid oxidation, was 10‐fold higher in the fermented product, and 2.4‐fold higher in the unrefined oils compared to MD products. Vitamin A concentrations in the MD products were 500–583 IU/mL with the exception of one product (1,086 IU/mL). The fermented product contained 1117 IU/mL, while the unrefined contained 611–2126 IU/mL vitamin A. Vitamin A2, the dehydroretinol form was only detected in fermented and unrefined samples in measurable amounts. Total sterols were lower in the fermented sample. Commercial MD products contain higher amounts of EPA/DHA than crude, while the fermented and crude products contain higher levels of vitamin A.
Dose‐Response Effect of Long‐Term Quercetin Supplementation on Metabolomics and Quercetin Conjugate Profile in Adults
Authors: Cialdella-Kam Lynn , Nieman David C. , Sha Wei , Meaney Mary Pat , Knab Amy M. , Shanely R. Andrew
Published: June 2021

Quercetin, a flavonol in fruits and vegetables, has been demonstrated to have antioxidant, anti‐inflammatory, and immunomodulating influences. Using a randomized double‐blinded placebo‐controlled trial, we examined if 2 different quercetin doses (500 or 1000 mg/d) would alter metabolic profiles and serum quercetin conjugate levels in adults (58 women and 42 men; 40–83y). Overnight fasted blood samples were collected at 0‐, 1‐, and 3‐mo and analyzed for metabolic profiles using 2 mass spectrometry platforms (UPLC‐QTOFMS and GC‐TOFMS) with partial least square discriminant analysis (PLS‐DA) and linear mixed model with repeated measures. After accounting for age, sex, and BMI, quercetin supplementation was associated with significant shifts in 163 metabolites/quercetin conjugates (FDR p‐value <0.05). The top 5 metabolite shifts were an increase in serum guaiacol, 2‐oxo‐4‐methylthiobutanoic acid, allocystathionine, and two bile acids. Inflammatory and oxidative stress metabolites were not affected. PLS‐DA revealed a clear separation only between the 1000 mg/d and placebo groups (Q2Y=0.763). The quercetin conjugate, isorhamnetin‐3‐glucuronide, had the highest concentration at 3‐mo followed by quercetin‐3‐glucuronide, quercetin‐3‐sulphate, and quercetin diglucuronide respectively. In humans, quercetin exerts disparate and wide‐ranging metabolic effects especially with 1000 mg/d dose.
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

Background

Pulses (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.

Methods

Six 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.

Results

PEAK 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.

Conclusion

Though 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.
High‐fat feeding leads to decreased responsiveness to the GLP‐1 analogue, exendin‐4, in obesity‐prone (OP) rats
Authors: Duca Frank , Sakar Yassine , Covasa Mihai
Published: June 2021

We have recently shown that diet‐induced obese rats exhibit decreased responses to nutrient‐induced satiation, and this was associated with diminished protein expression of several gut peptides, including GLP‐1. Exogenous GLP‐1, and its analogue exendin‐4 (Ex‐4) decrease food intake, however, it is not known whether obese prone (OP) rats have an impaired response to GLP‐1, that could contribute to decreased nutrient induced satiation and hyperphagia. Therefore, we examined the effects of Ex‐4 on food intake in OP and obesity resistant (OR) rats maintained on either chow or high‐energy/high‐fat (HE/HF) diet. When exposed to chow, there was no difference in 1h food intake between OP and OR rats following Ex‐4 (0, 0.625, 1.25, 2.5, and 5 μg/kg, IP). However, when fed the HE/HF diet, OP suppressed intake significantly less than OR rats at all Ex‐4 doses tested. Also, compared to OR, OP rats expressed less GLP‐1 protein in the intestinal epithelium irrespective of the maintenance diet. There was with no difference in fasting GLP‐1 circulating plasma levels between OP and OR rats. Finally, HE/HF feeding resulted in downregulation of GLP‐1 mRNA expression in the vagal nodose ganglia of OP rats. We conclude that feeding a HE/HF diet leads to impaired feeding responses to GLP‐1 in OP rats, which is associated with diminished gene expression in the vagal afferents.
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
Differences in pharmacological activities of the antioxidant flavonoid monoHER in humans and mice are caused by variations in its metabolic profile
Authors: Jacobs Hilde , Koek Ger H , Peters Ron , Moalin Mohamed , Tack Jan , van der Vijgh Wim J , Bast Aalt , Haenen Guido R
Published: June 2021

Despite its well‐known cardiotoxicity, the anthracycline doxorubicin continues to be a widely used chemotherapeutic agent. The flavonoid 7‐mono‐O‐(β‐hydroxyethyl)‐rutoside (monoHER) has shown protection against doxorubicin‐induced cardiotoxicity in mice. However, this protection has not been observed in humans. This prompted us to investigate monoHER metabolism in humans and compare it with that in mice. Five healthy volunteers received monoHER by intravenous infusion. After infusion, bile fluid was collected, and the monoHER metabolites were identified by liquid chromatography–diode‐array detection (LC–DAD), time‐of‐flight mass spectrometry (TOF‐MS), and 1H‐nuclear magnetic resonance (NMR). Thirteen different metabolites were identified. MonoHER was predominantly converted into inactive glucuronidated metabolites. In mice, the major metabolic route is methylation, which forms bioactive metabolites that are implicated in the cardioprotective effect of monoHER. This indicates that the different pharmacological effects of monoHER in mice and humans might be explained by a difference in monoHER metabolism. This study adds to the growing appreciation of flavonoid metabolites as bioactive compounds.
Glutathione S‐transferase (GST) M1 and Tl polymorphism influence plasma antioxidant status of Korean smokers after grape juice supplementation
Authors: Kang Myung-Hee , Lee Hye-Jin , Cho Mi Ran
Published: June 2021

Grape juice is a rich source of polyphenols, which have antioxidant properties. Glutathione S‐transferase (GST) belongs to a multigene family of phase II enzymes, which are involved in detoxification and function as antioxidants. In this study, we examined whether daily supplementation of grape juice can modulate the levels of plasma antioxidants, lipid profiles and conjugated dienes (CD), which are markers of lipid peroxidation, and whether this modulation can be affected by the GSTM1 and T1 polymorphisms. 95 male smokers received 480 ml/day of grape juice for 8 weeks, and blood samples were drawn before and after this 8 week period. Plasma levels of γ‐tocopherol increased and plasma CD decreased only in the GSTM1‐null genotype when compared to the GSTM1‐ present genotype after supplementation (p<0.05). Supplementation did not change the plasma levels of the other antioxidants and lipid profiles in GSTM1‐null or present genotypes. There were no significant changes in the plasma levels of antioxidants and lipid profiles for the GSTT1‐null or present genotypes after supplementation. Our findings suggest that supplementation of grape juice might increase plasma γ‐tocopherol levels and decrease lipid peroxidation in smokers with a GSTM1‐null genotype. (This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011‐0003613)).
The Effects of 24R, 25‐Dihydroxyvitamin D3 and 24S, 25Dihydroxyvitamin D3 on Phosphate Transport in Vivo
Authors: Meng Yu , Nemere Ilka
Published: June 2021

The steroid hormone 1, 25‐dihydroxyvitamin D3 [1,25D3] rapidly stimulates the uptake of phosphate in isolated chick intestinal cells, while 24,25‐dihydroxyvitamin D3 [24,25D3] inhibits the rapid stimulation by 1,25D3. in isolated intestinal cells and perfused duodenal loops. Studies were undertaken to determine if 24,25D3 had a similar effect in vivo. 24,25D3 has two isomers which are 24R, 25dihydroxyvitamin D3 [24R,25D3] and 24S, 25dihydroxyvitamin D3 [24S,25D3]. We studied these two isomers separately and tested them over a time course of 1, 5, 10, 15 and 18 h after steroid using chicks on regular diet, but fasted, and chicks on a lower vitamin D diet. All chicks were anesthetized prior to surgical exposure of the duodenal loop and injection of H3 32PO4 in buffer into the lumen. An initial study determined that 3 to 9 min of absorption in vivo was in a linear range, as judged by serum levels of radioactivity. Chicks were then injected IM with either 200 μg 24R,25D3, 20 μg 24S,25D3 or vehicle (1–18 h prior to experimentation) within the same time course studies. The isomers had different effects on phosphate absorption: 24R,25D3 had a hypophosphatemic effect in vivo in which serum levels at 5, 15 and 18 h had decreased to 42%, 39% and 43%, respectively, (P< 0.05) compared with controls. In contrast, 24S, 25(OH)2D3 stimulated intestinal phosphate absorption at the 5h time point by 64%, but had no effect at the other time points tested. Supported by Agriculture and Food Research Initiative Competitive Grant no. 2010‐65206‐20652 from the USDA National Institute of Food and Agriculture.
Omeprazol produces changes in blood calcium, phosphorous and magnesium after food ingestion in horses
Authors: Manso-Filho Hélio Cordeiro , Manso Helena Emília Cavalcanti C C , Mélo Stephânia , Lima Rebeca , DˈAraújo Juliana , Almeida Telga , Silva Flávia Souza e , Cortizo Julianne , DˈPaula Joyci , Wanderley Erika , Hunka Monica
Published: June 2021

Omeprazol (OMPZ) is used to prevent gastric ulcer syndrome in athletic horses. The aim of this research was to characterize changes in blood [Ca++], [P‐] and [Mg++] in ulcer‐free horses after omeprazol treatment. A Latin square design, with four horses and four treatments (T1: control, T2: 4mg/kg PO bolus treatment, T3: 1mg/kg PO during 11 days and T4: 4mg/kg PO during 11 days) was used. Blood was collected during fasting and 0.5h through 7.0h after feeding. Data were analyzed by two‐way ANOVA. It was observed decrease in [P] between treatments (P<0.05) but not change in [Ca] or [Mg] (P>0.05). Similarly, only [P] showed a significant difference between the phases of blood collection (P<0.05). There were no interactions between the phases of blood collection and treatments (P>0.05). These results demonstrated that OMPZ, which reduces pH of stomach, changed absorption of dietary P, reducing the serum concentration (T1: ~3,4mg/mL; T2: ~3,6mg/mL; T3: ~2,6mg/mL; T4: ~3,2mg/mL). In conclusion, treatment with OMPZ lowered serum [P] but not [Ca] or [Mg] in healthy horses. Changes in blood mineral parameters are important in athletic horses, which are undergo intense bone adaptation in response to exercise.
Influence of dietary carbohydrate source and high fat on reproductive tract characteristics of prepubertal female pigs
Authors: Xie G. , Reeves H.F. , Deaver S.E. , Dixon K.A. , Escobar J. , Rhoads R.P. , Rhoads M.L.
Published: June 2021

The objective was to assess reproductive tract characteristics of prepubertal female pigs receiving diets that differed in carbohydrate (CHO) source. For 8 weeks, pigs (28d‐old) were fed either Control or high‐fat (HF) diets. HF diets contained either complex (Corn) or simple (Glucose or Fructose) CHO. Control pigs were pair‐fed with HF pigs resulting in similar final body weight across treatments (P=0.81). Ultrasound backfat depth (indicative of body adiposity) was 84% higher (P<0.001) in HF, and simple CHO diets tended to increase backfat (P=0.11). Pigs receiving HF diets have heavier (P=0.08) ovaries containing more antral follicles compared to Control. Further, simple CHO diets resulted in heavier uteri and ovaries and more antral follicles (P<0.01) compared to Control or complex CHO. HOMA‐B was negatively correlated (P=0.05) with ovarian weight and tended (P=0.10) to be negatively correlated with total tract weight. Total tract weight was positively correlated (P=0.07) with fasting glucose levels. Thus, observed reproductive differences among treatments appear to be related to metabolic status. Greater tissue weights and antral follicle numbers indicate that pigs receiving simple CHO diets may have been maturing more quickly from a reproductive standpoint, and would have likely ovulated before their counterparts. College of Agriculture and Life Sciences
Neutrophil infiltration related to the methotrexate‐induced intestinal barrier dysfunction
Authors: Horie Toshiharu , Asada Chiaki , Kakigawa Naoko , Sekine Shuichi
Published: June 2021

Objective

Methotrexate (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.

Methods

T84 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.

Results

PMN 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.

Conclusions

MTX 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.
Weaning weight and impact on innate immunological status of beef cattle
Authors: Preston Whitney Dawn , Fergerstrom Marla , Fukumoto Glen , Sy Tracy , Abran Melelani , Stokes Ashley Michelle
Published: June 2021

Weaning is considered one of the most stressful events in the life of beef cattle and can impact health and growth, therefore examination of its effects on innate immunity is needed. An animal with depressed immunity is susceptible to disease, can have poor growth, and increased morbidity and/or mortality during stressors. We isolated leukocytes and evaluated gene expression of components of the Toll‐like Receptor (TLR) Signaling Pathway. Beef calves (Angus, Hereford, and Angus‐cross breeds) were placed into groups of early (400lb), standard (500lb), and late weaned (600lb) animals. Blood samples were taken at birth, 1 month pre‐weaning, and 1 month post‐weaning. TaqMan PCR was conducted for TLR‐2, TLR‐4, PI3KR1, IKBα, TNFα, IL‐1β, IL‐8, MyD88, CASP8, p38, JNK, substance P precursor, and COX2 with housekeeping genes 18S and GAPDH. Final data is pending, however findings suggest increased expression of pro‐inflammatory and immunological mediators after weaning, yet no difference in expression found between weaning groups. Results may impact current weaning methods in tropical systems. Funded by the University of Hawaii at Manoa, College of Tropical Agriculture and Human Resources.
Plasma kininogen and bradykinin receptors are required for collagen antibody‐induced arthritis (CAIA)
Authors: yang aizhen , Xie Zhanli , Zhu Xuemei , Wu Yi
Published: June 2021

Studies in experimental and clinical arthritis have suggested that plasma kallikrein‐kinin system (KKS) plays an important role in the pathogenesis of arthritis, however, the elucidation of the underlying mechanisms awaits further investigation in gene deficient mouse model. High molecular weight kininogen (HK) is a major component of KKS, the activation of which induces HK cleavage to generate bradykinin (BK) and active form of HK (HKa). BK and HKa are both proinflammatory. In this study, we used a kininogen‐1−/− (Kng1−/−) mouse strain we newly generated and double BK receptors knockout (B2RB1R−/−) mice. In mice Kng1 gene drives the production of HK in plasma. Removals of Kng1 gene and plasma HK protein of Kng1−/− mice were confirmed by RT‐PCR and Western‐blotting, respectively. To induce CAIA, three groups of mice (WT, Kng1−/−, and B2RB1R−/−) were injected intraperitoneally with anti‐type II collagen antibody cocktail (3 mg) on day 0 and LPS (50 μg) on day 3. WT mice started to develop joint swelling and erythema on day 5, and the increase in ankle joint diameter became marked on day 6 (1.32±0.13 mm) and peaked on day 8 (1.41±0.17 mm). In contrast, either Kng1−/− or B2RB1R−/− mice did not develop joint arthritis (p<0.01). Our results for the first time demonstrate an essential role of plasma HK in the pathogenesis of arthritis, and BK is a key mediator. Blockade of HK cleavage could be an attractive anti‐arthritic treatment.
Induced myeloperoxidase activity in ovarian cancer mouse model
Authors: Papineni Rao V , Mor Gil , McLaughlin William , Holmberg Jennie , Craveiro Vinicius
Published: June 2021

Promotion of neutrophil‐mediated inflammation at the tumor enhances the anti‐tumor immune response. Here we investigated the possibilities of using nutriceuticals in induction of myeloperoxidase (MPO activity) in a tumor mouse model. We monitored in vivo MPO activity in a intraperitoneal ovarian cancer tumor mouse model by injecting (i.p) luminol. Multimodal imaging at different time points were performed to determine both the progression of the intraperitoneal tumor metastasis (fluorescence) and the MPO activity (lumiscence). The results show that basal MPO activity signal was not uniform between the tumors, and in some tumors, the MPO activity was completely absent indicating the presence of a differential tumor microenvironment within the mouse. Enhancement in MPO activity was observed upon administration of a single dose of 0.1 ml (50% volume/volume) of nutriceutical‐ BV9 (i.p injection). BV9 elicited a robust increase in the MPO activity within 3 hrs of its administration and the luminescence signals co localized with the tumors. Further investigations assessing the role of elicited MPO activity in cancer progression will greatly enhance the understanding of the tumor microenvironment and aid in better cancer treatments.
Conditioned taste aversion elicited by synthetic cannabinoid JWH‐018 in mice is attenuated by pretreatment with phytocannabinoid Δ9‐THC
Authors: Hyatt William S. , Zimmerman Sarah M. , Fantegrossi William E.
Published: June 2021

Aminoalkylindole cannabinioids have recently emerged as drugs of abuse in the US and worldwide. Perhaps the most common such compound present in commercial K2/Spice blends is JWH‐018. The effects of these smoking blends are often more intense than those of marijuana, likely because the aminoalkylindoles have higher affinity for and efficacy at CB1 cannabinoid receptors. Indeed, adverse reactions including agitation, paranoia, tachycardia, seizure, and even death have been reported following exposure to K2 products containing JWH‐018. To model the aversive effects of JWH‐018, we used a conditioned taste aversion procedure in mice. Briefly, mice were trained to emit an operant response (nose‐poke) reinforced with evaporated milk under a fixed‐ratio 5 (FR5) schedule. When responding became regular and reliable, the evaporated milk was replaced with a strawberry‐flavored milk solution; immediately after this session, mice were injected with 3 mg/kg JWH‐018. At least three evaporated milk recovery sessions occurred between strawberry‐flavored milk exposures. Separate groups of animals were treated with the phytocannabinoid Δ9‐THC prior to the first strawberry‐flavored milk exposure. In mice lacking a Δ9‐THC history, JWH‐018 elicited a robust and persistent taste aversion to the strawberry‐flavored milk which was apparent after a single pairing. Interestingly, mice pretreated with Δ9‐THC developed a less intense and shorter‐lived taste aversion following exposure to JWH‐018. These studies suggest that JWH‐018 has pronounced aversive effects, and that these effects may be more prominent in users who have no previous history of marijuana use. This work was supported by US PHS Grant RR020146, and by National Center for Research Resources grant 1UL1RR029884.
Enhanced Δ9–THC precipitated withdrawal in desensitizationresistant S426/430A mutant mice
Authors: Cook Alex J. , Morgan Dan J. , Mackie Ken
Published: June 2021

Δ9‐THC and other cannabinoid agonists have been reported to induce rewarding effects and physical dependence in several different animal models. In this study, desensitization–resistant CB1 “knock‐in” mice were used to determine whether this “hyper‐sensitive” form of CB1 would cause more sever symptoms associated with precipitated withdrawal (physical dependence). These mice contain two point mutations in C‐terminus of the CB1 receptor where serines at residues 426 and 430 have been substituted for non‐phosphorylatable alanines (S426/430A). Withdrawal was measured in wild‐type, CB1 knock‐out and S426/430A mutant mice after administering two daily injections of 50 mg/kg Δ9–THC over a period of six consecutive days. Withdrawal symptoms were precipitated using 10 mg/kg of rimonabant, a selective inverse agonist for CB1. Behavioral manifestations of withdrawal (head shakes, paw tremors, jumps) were recorded and scored by a trained observer blind to genotype. Our results demonstrate a significant increase in paw tremors and jumps, two measures of cannabinoid withdrawal, in S426/430A mutant mice relative to wild‐type littermate controls. In addition, all symptoms of precipitated withdrawal are absent in mice lacking the CB1 receptor. Our results suggest that that dependence for Δ9– THC is enhanced in desensitization‐resistant S426/430A mutant mice.
Further characterization of dopamine D2/D3 receptors and cocaine self‐administration in socially housed female monkeys
Authors: Duke Angela N , Nader Susan H , Riddick Natallia V , Czoty Paul W , Nader Michael A
Published: June 2021

Previous research in male subjects has shown an inverse relationship between vulnerability to drug abuse and dopamine D2/D3 receptor availability as measured with positron emission tomography. However, in female monkeys, this relationship appears opposite. Dominant female monkeys had higher D2/D3 receptor availability than subordinates, but acquired cocaine reinforcement at lower doses. These sex differences are of significance because they imply different treatment strategies in males vs. females (increase vs. decrease D2/D3 receptor availability, respectively). In the current study, we examined the relationship between D2/D3 receptor availability and responding maintained by food and cocaine in socially housed females. There was no relationship between D2/D3 receptor availability and food‐maintained response rates. However, females with high D2/D3 receptor measures had significantly higher cocaine‐maintained response rates using the lowest dose that functioned as a reinforcer (r2=0.30, p <0.05). In male monkeys the relationship is inverse. Ongoing studies with females will determine whether this relationship between D2/D3 receptors and cocaine reinforcement is a trait variable or related to the formation of social rank (i.e., a state variable). Altogether, these findings support the examination of treatment strategies that consider the sex of the individual.