bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of regulatory T cells and Th17 cells in ovarian endometriosis and ovarian epithelial tumors
Authors: Vlad Anda Mioara , Budiu Raluca , Thaller Julia , Edwards Robert P. , Finn Olivera J.
Published: June 2021

Endometriosis is a chronic inflammatory disorder defined as abnormal growth of endometrial tissue at ectopic sites, most often on the ovary. Women with endometriosis are at higher risk of developing ovarian cancer. We recently generated a mouse model for ovarian endometriosis, using the previously established LSL‐KrasG12D mice, which we crossed with MUC1 transgenic mice. Following intra‐bursal administration of Cre‐encoding adenovirus, the MUC1Kras mice develop de novo, endometriosis‐like lesions. Interestingly, these mice show an increased percentage of FoxP3+ regulatory T cells in their spleens and para‐aortic lymph nodes but fewer Th17.

We also investigated the pattern of FoxP3, IL‐17, TGF‐b, IL‐1 and IL‐6 mRNA expression in human ovarian endometriosis and ovarian cancer using qRT‐PCR. Our results from a total of 23 patients (normal donors, physiological ovarian cysts, endometriosis, ovarian tumors with paired ascites) show that FoxP3 was detected in the ascites of all tested patients and in the majority of tumor specimens but also in 6 out of 9 of patients with endometriosis, confirming our results in mice. IL‐17 was also up‐regulated in 55% of endometriosis cases and it was highly up‐regulated in ovarian cysts. Further studies on the immune imbalance in premalignancy (endometriosis) and ovarian cancer in mice and humans are in progress. Research support from the Continuing Medical Research Fund (AMV).
Interferon Regulatory Factor 8 Mediates Apoptosis via Regulation of Fas and FLIP Expression
Authors: Yang Dafeng , Thangaraju Muthusamy , Browning Darren D. , Dong Zheng , Korchin Borys , Levi Dina C. , Ganapathy Vadivel , Xiong Huabao , Liu Kebin
Published: June 2021

IRF8 is a transcription factor that was originally identified in myeloid cells. Mice with a null mutation of IRF8 exhibit uncontrolled expansion of myeloid cells that progress into a phenotype resembling human chronic myelogenous leukemia (CML). In human patients with CML, IRF8 transcript levels are frequently diminished. Here, we report that disruption of IRF8 function diminished Fas‐mediated apoptosis in solid tumor cells. Furthermore, it was found that constitutively expressed IRF8 is associated with the Fas promoter to activate Fas transcription. In addition, disruption of constitutively expressed IRF8 function diminished JAK1 expression and thereby inhibited IFNγ‐initiated induction of STAT1 phosphorylation. Interestingly, the constitutively expressed IRF8 was also essential for TNF‐α‐sensitization of Fas‐mediated apoptosis since disruption of IRF8 function also inhibited TNFα‐sensitized and Fas‐mediated apoptosis. Analysis of IRF8‐deficient dendritic cells (DC) generated from IRF8 null mice revealed that Fas expression level is also down‐regulated as compared to the wild type mice. In addition, IRF8‐deficient DCs also exhibited higher level of FLIPs protein as compared to the control wt DCs. Taken together, our data suggest that IRF8 is an essential regulator of Fas‐mediated apoptosis and that IRF8 mediates apoptosis through regulation of Fas and FLIP.
Human Milk Oligosaccahride Extraction
Authors: Yeung Henry Fan , Gillies Laura A. , German Bruce J.
Published: June 2021

Milk is a food emerged through by Darwinian pressure to ensure the genetic success of offspring. A remarkable and yet understudied component of milk are oligosaccharides. They have been hypothesized to act as a prebiotic because they are non‐digestible by infants, yet, they are the third most abundant sugar in human milk. A key problem limiting the study of this nature is the lack of methods to isolate oligosaccharides from other compounds, especially lactose. Analytical chemistry requires only a minuscule amount of oligosaccharide; however, biological studies will require larger quantities of oligosaccharide. Previous extraction methods proposed are gel filtration, nano filtration, and solid phase extraction. Methods suitable for industrialized machinery to process liters of human and other mammalian milks were developed on top of extraction methods modified after the solid phase extraction technique to yield gram per quantities of oligosaccharides.
Food choices of young women by level of cognitive dietary restraint
Authors: Bedford Jennifer Lynn , Barr Susan Irene
Published: June 2021

The purpose of this study was to compare young women's dietary intakes and usual food choices by level of cognitive dietary restraint (CDR). 135 healthy, non‐obese, 19–35 yr old women completed questionnaires including the Three Factor Eating Questionnaire – Restraint subscale (TFEQ‐R; Stunkard & Messick, 1985) and the Diet History Questionnaire (DHQ; NIH, 2002) which assesses qualitative and quantitative usual dietary intake. Data were analyzed by CDR level (low, mid, high). Energy, carbohydrate and fat intake did not differ by CDR level. Protein intake (absolute and relative) was higher among restrained eaters as were energy‐adjusted niacin, vitamin E, sodium, selenium, magnesium and iron intakes. Food group serving numbers did not differ by CDR level except that meat product intake was higher for restrained eaters (specifically, poultry and fish/seafood intakes were higher while red meat intakes were similar). Women with high CDR reported a lower frequency of eating hamburgers, chips, French fries, chocolate, ice cream, and candy but a higher frequency of soft drink use. The fat used during food preparation did not differ in frequency of use or usual type chosen. Those with high CDR were more likely to choose diet soft drinks and light/fat‐free options for ice cream and salad dressing, but did not differ in use of light/fat‐free options for meat, snacks or added fats, or high fiber options for grain products. While women with high CDR appear to avoid foods typically considered “less healthy” or “fattening”, their energy and quantitative nutrient intakes are generally similar to those with lower CDR. Supported by CIHR 79563
High dietary energy intake during pregnancy increases net gestational weight gain in overweight and obese women
Authors: Rahn Maike , Strawderman Myla S , Olson Christine M
Published: June 2021

Limited information is available about the relationship between dietary energy intake and gestational weight gain. Three hundred and twenty‐six women from rural New York participated in a prospective observational study. Dietary intake (Willet FFQ), physical activity level and SES were assessed once with mail‐in questionnaires between the 1st and 3rd trimester; maternal gestational weight gain (GWG), maternal height and infant birth weight were collected with chart reviews. Women with underweight BMI, inadequate GWG or inconsistent reporting of dietary intake were excluded. Energy balance (EB) was created by subtracting estimated total energy expenditure from dietary energy intake (EI); EB was categorized into negative, adequate and positive balance groups (cutoffs −300 and 300 kcal). Women were on average 28 years old, and 43% had a high BMI of >26 kg/m2. Mean GWG was 33.7±9.5 lbs, and 54% experienced excessive GWG. Mean net GWG was 25.6±9.4 lbs. Reported mean EI was 2480±756 kcal, mean EB was −102±817 kcal. EB and EI were highly correlated (r=0.9, p=0.03). EI tertiles were associated with net GWG in the overall group (trend p<0.05), but not in the BMI subgroups. Energy balance was associated with GWG and net GWG (trend p<0.05) in the overall sample; however, when separating normal and high BMI women, only the group with BMI >26 kg/m2 showed a significant increase (trend p<0.05) of GWG and net GWG with EB. High BMI women had a mean GWG of 29, 32, and 33 lbs for the negative, adequate and positive balance groups, respectively. Mean net GWG was 20, 24, and 25 lbs, respectively. In conclusion, increased dietary energy intake results in greater net GWG, but only in high BMI women.

This research was supported by the NIH postdoctoral grant R21 DK69448.
Examining the dietary amino acid characteristics of patients on ketogenic therapy
Authors: Nathoo Sunina , Borum Peggy R.
Published: June 2021

Ketogenic Therapy (KT) is a high fat, adequate protein, low carbohydrate diet shown to reduce seizures in patients with intractable epilepsy. While KT has been used for decades, the building blocks of the dietary components such as amino acids have not been examined. The usual diet prescription ratio of grams of fat to grams of carbohydrate plus grams of protein assumes that the all protein is the same and has the same effect on the therapy as carbohydrate. To evaluate dietary protein characteristics in patients on KT, data were collected via weekly 24 hour dietary recalls taken from 14 patients on KT. The Minnesota Database (NDS) was used to analyze these recalls. Some of the dietary protein characteristics are listed in the table below.

The characteristics of dietary amino acids vary among pediatric patients on ketogenic therapy for seizures. Characteristics such as the ratio of ketogenic amino acids to gluconeogenic amino acids may impact the therapy and these potential impacts need to be evaluated.
Evaluation of metabolism‐boosting beverages on resting energy expenditure
Authors: Coleman Christopher D. , Rampolla Joni , Kiel Jessica , Davis Lisa M.
Published: June 2021

Objective: To evaluate the effect of thermogenic meal replacement beverages (TMRB) containing 90mg ECGC and 100mg of caffeine on resting energy expenditure (REE).

Subjects: 30 adults (19 women, 11 men) were stratified into 3 groups: lean (n=10, BMI 21.5 ± 2.1); overweight/obese (OW) (n=10, BMI 29.8 ± 2.7); or weight maintainers (WM) (n=10, BMI 28.8 ± 4.0, maintained wt loss of ≥5% body wt for ≥3 mos).

Methods: Following an overnight fast, baseline measures of ht, wt, WC, bp, pulse, and REE via indirect calorimetry were performed. REE was repeated at 30, 60, 90, and 120 min after consuming a TMRB. Appetite was assessed via visual analogue scale at baseline, 30 min and 120 min after consuming the TMRB.

Results: Overall, mean REE increased 24.0 ± 10.1% for the 2‐hr period following the consumption of a TMRB. Mean 24‐hr REE was increased 5.9 ± 2.5% overall (p=0.000), 5.7 ± 3.1% among lean subjects (p=0.0002), 5.3 ± 1.4% among OW subjects (p=0.000), and 6.8 ± 2.7% among WM (p=0.0007). There was a trend toward increased fat oxidation (p=0.116). Appetite was significantly reduced 30 min after consuming the TMRB (p=0.0002), but not at 120 min.

Conclusion: Our findings suggest 3 potential benefits of TMRB in weight control: increases in resting energy expenditure, increases in fat oxidation, and decreases in appetite. Decreases in energy in and increases in energy out should translate into improved weight loss and weight maintenance.
Glycemic index of raw versus cooked food bars
Authors: Rudell Deborah , Rylander Astrid , Uribe Cisca , Engelhardt Sarah , Kubica Andrea , Villalobos Fatima , Nemoseck Tricia , Stocker Kelly , Kern Mark
Published: June 2021

Glycemic index (GI) classifies foods by the extent that their ingestion affects glucose responses, and diets with lower GI foods may reduce chronic disease risk. Proponents of raw foodism suggest that raw foods provide such advantages but this concept is supported by limited research. This study was conducted to compare the GIs of two different commercial raw food bars (Larabar®) containing either dates, walnuts, apples, almonds, raisins, and cinnamon (Apple Pie) or cashews and dates (Cashew Cookie) consumed either raw or cooked (baked at 350°F for 15 min). Food portions containing 50 g of carbohydrate from a glucose solution (tested in triplicate) and the 4 trials of test foods were administered in random order to 15 healthy adult women after at least a 4‐hour fast. Capillary blood samples were collected at baseline and 15, 30, 45, 60, 90 and 120 min after consumption and assessed for glucose concentration. GI values were calculated from the incremental area under the curve by the trapezoidal method. Data were analyzed using paired‐comparisons t‐tests between raw versus cooked varieties of each bar. GI (mean±SD) was higher (p≤0.05) for the cooked (64±40) Apple Pie bar than its raw (42±32) counterpart. No difference was detected for cooked (42±24) or raw (39±20) Cashew Cookie bars. Cooking appears to raise the GI of some, but not all, food; therefore, research is needed to establish which foods yield elevated GIs after cooking.
Fruit, Vegetable consumption and Body Weight
Authors: Pereira Paula Cardoso , Vicente Ana Filipa
Published: June 2021

Low fruit and vegetable consumption has been associated with other erratic food habits which lead to overweight and obesity. In the present study, we compare weight and body mass index (BMI) with vegetable soup, vegetables as side dish and fruit consumption.

A total of 25 men had their weight and height measured, we calculated their BMI and obtained vegetable and fruit consumption by food diary and average intake recall.

This data showed that only 10% were in their normal weight but even obese and overweighed men had healthy habits about vegetable and fruit consumption. The vast majority reported that it was an habit to consume vegetable soup in 1 to 2 meals but vegetables in both main meals (lunch and dinner). Fruit intake reported accomplished even more WHO recommendations (1 – 3 servings/day).

Several secondary aspects can influence these men's food choices, mainly soup and vegetable availability where they eat. This results may show that even overweighed and obese can have some healthy food habits.
Opposing effects of methylmercury and n‐3 long‐chain polyunsaturated fatty acids on oxidative status
Authors: Craig‐Schmidt Margaret C , Teodorescu Carmen A. , Colbert Katie E. , Newland M. Christopher , Huggins Kevin W.
Published: June 2021

The objective was to assess interactive effects of methylmercury (MeHg) and n‐3 long‐chain polyunsaturated fatty acids (LCPUFA) on oxidative status of animals exposed chronically to MeHg and fed a diet with (+) or (−) without n‐3 LCPUFA. Female rats (n=8/grp) were exposed for 1 yr to 0, 0.5, & 5 ppm MeHg in water and consumed a diet containing palm, safflower, soybean and either coconut in (−) n−3 diet or fish oil in (+) n‐3 diet. The expression of the pro‐oxidative enzyme NADPH oxidase (OX) and antioxidant enzymes glutathione peroxidase (GSH‐Px), catalase (CAT), and superoxide dismutase (SOD) were determined using RT‐PCR. Protein oxidation was assessed by measuring protein carbonyl content. The (+) n−3 groups had significantly lower gene expression of OX than (−) n−3 groups (P ≤ 0.001) in both heart and liver. A mercury effect was observed for this enzyme in the liver (P = 0.01), with increased prooxidant activity with MeHg. The n‐3 fed animals without MeHg have decreased oxidized protein content in heart by 35% compared to (−) n−3 group. No overall diet effect was observed in gene expression of any of the antioxidant enzymes. In the liver, presence of MeHg decreased antioxidant activity as reflected in gene expression of GSH‐Px (P = 0.05) and CAT (P = 0.005). The opposing effect of environmental contaminant, MeHg, and n‐3 LCPUFA in fish may be explained, in part, through changes in oxidative status. (Funded by AAES 13–014)
Comparative Effects of Dietary Oils on Markers of Insulin Sensitivity in Postmenopausal Women with Type 2 Diabetes
Authors: Norris Leigh , Colleen Angela , Asp Michelle , Liu LiFen , Hsu Jason , Li Dongmei , Bell Doris , Osei Kwame , Jackson Rebecca , Belury Martha A.
Published: June 2021

Dietary fatty acids have been implicated in the development of obesity and insulin resistance. This was a 36‐ week controlled, double masked randomized crossover study, to observe the effects of conjugated linoleic acid (CLA) and safflower oil (SAF) on markers of insulin sensitivity. Fifty‐five obese postmenopausal women with type 2 diabetes (T2DM) received 6.4 g mixed isomer CLA and 1.6 g SAF per day or 8.0 g SAF daily. Analyses of results at individual 5% level of significance were as follows. During diet period one (DP1), C peptide area under the curve was significantly higher while glycosylated hemoglobin and fasting glucose were significantly lower with SAF supplementation. There appeared to be no effect of CLA. Insulin sensitivity was improved in both diet periods by SAF as shown by a significant increase in quantitative insulin‐sensitivity index and significant decrease in HOMA assessment. In addition, SAF significantly reduced trunk adiposity and increased lean tissue as measured by DEXA. CLA had no significant effects on trunk adiposity. Dietary energy intake remained constant throughout the study. Reporting of adverse events did not differ between groups. In conclusion, CLA does not seem to affect insulin sensitivity, while SAF improves insulin sensitivity, which may be due to a reduction in visceral adiposity, in postmenopausal women with T2DM. Supported by Cognis GmbH.
Effect of long‐term caloric restriction on mitochondrial function in skeletal muscle and non‐exercise activity in aged rats
Authors: Schimke Jill M , Walrand Stephane , Klaus Katherine A , Morse Dawn , Short Kevin R , Novak Colleen , Levine James A , Nair K. Sreekumaran
Published: June 2021

Aging is associated with a concomitant decline in non exercise activity (NEA) and mitochondrial ATP production rate (MAPR) in skeletal muscle. To determine whether caloric restriction (CR) could prevent the decline in MAPR and NEA we studied young (Y, 7 month‐old, n=8), old (O, 27 month‐old, n=7) and old caloric‐restricted F344/BN rats (OCR, 27 month‐old, 40% CR from 16 weeks of age, n=7). Energy expenditure (kcal/d/gBW) was lower in O (0.311±0.005) than Y (0.365±0.004) and was higher in OCR (0.341±0.008) (P<0.05). Muscle mass (mg/gBW) of O was lower than Y, and Y and OCR are similar (Y=0.96±0.18, O=0.71±0.16, OCR=1.03±0.04; P<0.05 OCR vs O). Citrate synthase activity and MAPR were lower in both O and OCR than Y (P<0.05). UCP3 protein level was higher in soleus and plantaris muscles from O rats than Y and OCR (p<0.005). CR lowered UCP3 expression in skeletal muscles to the level in Y rats (p<0.005 OCR vs O). CR also lowered expression of mRNA levels of NADH4 (p<0.005 OCR vs O). NEA levels were lower in O and OCR rats than in Y (p<0.05 Y vs O and OCR). In conclusion, the decline in mitochondrial functions during aging can be counteracted by CR but an age‐related decline in activity levels could not be prevented. Funded by NIH RO1 AG09531 and Mayo Foundation.
Walking as a complement to hypocaloric diet leads to greater weight loss in early‐postmenopausal overweight women
Authors: Ilich Jasminka Z , Pounds Susan , Liu Pei‐Yang , Shin Hyehyung , Humphrey Kristen , Crombie Aaron P , Dutton Gareth
Published: June 2021

In efforts to curb overweight, different dietary and/or physical activity regimens are employed. We examined success of a weight‐loss protocol during 3 months. Subjects were 33 Caucasian, healthy, overweight, early‐postmenopausal women. Weight‐loss protocol consisted of energy restriction with calcium supplements (or placebo in double blind design) and/or low‐fat dairy foods. In this preliminary analysis, data from all participants were pooled, however, calcium intake was controlled for in statistical analyses. Subjects were also encouraged to increase walking, but strenuous exercise was not allowed. Parameters assessed at baseline and 3 months were: height, weight (BMI), walking (by survey and expressed as hr/week), and 3‐day dietary records. Participants lost ~3% weight and dropped from 83.7±12.8 to 80.3±12.4 kg (BMI from 31.6 to 30.3 kg/m2). Walking increased from 1.4±1.9 to 2.7±3.1 hr/week. Multiple regression models with % weight difference as dependent variable and controlled for energy and calcium intake, revealed that participants who walked more were able to lose more weight (p=0.05). In conclusion, even low number of hours of walking/week (2.7) made difference in weight loss outcomes in this population. These results indicate that dietary intervention in weight loss regimens should be complemented by walking, as a relatively easily achievable and widely popular mode of physical activity.
Who's Eating Spinach Again?
Authors: Dellava Jocilyn E. , Cuite Cara L. , Hallman William H.
Published: June 2021

In September of 2006, the Food and Drug Administration issued an advisory warning against the consumption of fresh spinach due to contamination with E. coli 0157:H7. Subsequently, spinach was largely recalled by manufacturers. Spinach is a healthful, nutrient dense food. Generally, low income and African American groups have low quality diets lacking in healthful items. Therefore, the objective of this report is to determine if persons in these groups who ate spinach prior to the recall were less likely to consume spinach in the weeks following the recall.

A national telephone survey of 1200 Americans was conducted in November, 2006. Within two weeks of the recall's end 55% of participants that ate spinach before the recall and heard about the recall had not returned to eating spinach. Using Student's t‐tests, factors associated with a lower likeliness of eating spinach immediately following the recall include African American ethnicity (p ≤ 0.001) and having an income less than 35,000/yr p ≤ 0.000.

Overall, groups with traditionally poor quality diets were less likely to return to eating spinach in the weeks following the recall. Since this study only assessed spinach consumption following the recall in participants that consumed spinach before the recall, it is likely the recall had more adverse effects on these groups that are all ready at risk for unhealthy diets.

Funding Source: Cooperative State Research, Education, and Extension Service of the United States Department of Agriculture under the National Integrated Food

Safety Initiative: Grant # 2005‐51110‐02335.
Relation between lifestyle factors and anti‐fat attitudes in college students
Authors: Kennedy Tay , Felts Emily , Parker Stephany , Topham Glade
Published: June 2021

Overweight individuals are affected by prejudice. This study examined antifat bias and body image dissatisfaction and their relation to body mass index (BMI) among college students. Height and weight were measured in 187 (78% female) college students between the ages 18–24. Antifat bias was assessed using Crandall's antifat attitudes (AFA) questionnaire and body dissatisfaction was assessed using Davison and McCabe's questionnaire. Differences between genders were found for all three subscales of the AFA questionnaire: females were found to have a higher Fear of Fat than males (p=.000), males possessed a higher level of Dislike for overweight individuals (p=.004), and males attribute overweight to a Lack of Willpower more readily than did females (p=.010). BMI and the Fear of Fat were positively correlated even after controlling for gender (R=.252, p=.001) and there was a significant difference among BMI groups (BMI<19, BMI 19 to 25, BMI>25) in Fear of Fat scores (p=.005). A positive relationship between total AFA scores and total Body Image scores (R=.457, p=.000) was discovered and supports the view that as one's opinion about their own appearance and/or weight becomes more positive, their attitude toward overweight and obese people becomes more negative. Males appear to be more extreme in their attitudes toward overweight individuals.
Compliance to an Exchange‐list Mediterranean Diet
Authors: Djuric Zora , Ren Jianwei , Radakovich Katherine , VanLoon Glee , DiLaura Nora Mary , Sen Ananda
Published: June 2021

A Greek‐Mediterranean dietary pattern has great potential for cancer prevention. We developed an exchange list diet that would target key nutrient intakes of the Mediterranean eating pattern. The goals were to replace half of usual polyunsaturated fat intake with monounsaturated fats (MUFA) and to increase intakes of a wide variety of fruits and vegetables, including dark green vegetables, allium vegetables and herbs. A total of 69 women, ages 25–59, were enrolled in the study and randomized to the Mediterranean diet or not for 6 months. Subjects in the Mediterranean diet arm received individualized telephone counseling. Menus were provided as examples, but the diets were self‐selected. Compliance to the dietary goals was assessed by 7‐day food records and by levels of plasma fatty acids, lipids and carotenoids. The women were able to make large changes. Intake of MUFA increased by 48% without a change in overall fat intake. Fatty acids levels in plasma changed in the same direction as dietary fatty acids, but were smaller in magnitude. Intakes of carotenoids more than doubled in the Mediterranean diet arm, and plasma total carotenoids increased by 65%. A statistical model was developed to identify clustered outcome variables. This modified Mediterranean diet will be tested for its effects on markers of cancer risk in future studies.

Supported by AICR grant #03B043.
Home and community‐based trial implemented by college mentors prevents overweight among urban adolescents
Authors: Black Maureen , Hager Erin , Shebl Fatma
Published: June 2021

Objective: Conduct RCT of health promotion among low‐income, urban adolescents (11–14 yrs). The 12‐session home and community intervention was implemented by college mentors. Method: BMI was measured. Dietary patterns were measured with the Youth Adolescent Food Frequency Questionnaire, and physical activity was measured by accelerometry. Adolescents were randomized into intervention (121/235) or control (114/235). Evaluations were conducted at baseline, post intervention (PI), and 2 years after baseline. Results: Retention over 2 years was 76%. At baseline 39% were at risk/overweight (OWT, BMI ≥ 85th %ile). After 2 years, rates of OWT declined 2.4% in the intervention and increased 12.1% in the control, OR=7.97, p=.007. Using GEE, intervention adolescents were less likely to advance to OWT than control adolescents, χ2=5.8, p=0.02. The decline in snacks/desserts was greater in intervention than in control (b=0.31, F=7.21, p=.007). Changes in play‐equivalent physical activity (PEPA ≥ 1800 activity counts/min) were moderated by BMI. Among youth who were OWT at baseline, PEPA decreased among control and increased among intervention, F=4.12, p=.03 at PI. There were no differences at 2 years. Conclusion: A home‐ and community based intervention delivered by college mentors prevented BMI increase, decreased snack/dessert consumption, and protected the heaviest youth from a decline in physical activity.
The effect of calcium status on the immune function of ovariectomized rats
Authors: Son Eunwha , Choi Hyesook , Do Hang , Kim Mihyun , Pyo Suhkneung
Published: June 2021

Mineral supplements are helpful for strong bones and the immune system plays an important role in postmenopausal stimulation of bone loss. This study examined the effect of calcium‐deficiency diet on immune functions and cell viability in ovariectomized rats (OVX). The treatments were as follows: Group 1, sham/AIN‐93M diet(0.5% Ca diet); Group 2, low‐Ca diet (0.25% Ca);Group 3, OVX/AIN‐93M diet; and Group 4, OVX/low‐Ca diet (0.25% Ca). The treated rats were sacrificed after 10 wks. In vitro lymphocyte proliferative responses and NK cell activity were measured in pooled spleen from each group. The mitogenic activity of lymphocytes in the spleen was slightly reduced in low‐Ca diet group. Ovariectomy caused a little decrease in the tumoricidal activity of NK cells, whereas low‐Ca diet resulted in the increase of tumoricidal acitivity. Ovariectomy caused the decrease of reactive oxygen species and NO production by macrophages. In contrast, low‐Ca diet induced the increase of tumoricidal activity. Moreover, ovariectormy marginally increased cell viability, whereas cell viability was reduced in group receiving low‐dose Ca supplement. Cell death was more pronounced in OVX on low Ca diet. Overall, our data suggest that calcium status of the animal has a differential effect on the function of immune cells. (This work was supported by grant No. RTI05‐01‐02 from the Regional Technology Innovation Program of MOCIE)
A combined marginal deficiency of copper and zinc does not exacerbate oxidant stress associated with copper or zinc deficiency
Authors: Nielsen Forrest H
Published: June 2021

Both copper deficiency (Cu‐def) and zinc deficiency (Zn‐def) result in oxidative stress. Thus, an experiment was conducted to determine whether a marginal Zn‐def amplified oxidative stress responses to a marginal Cu‐def, or vice versa. Weanling male Sprague‐Dawley rats were assigned to groups of 10 and fed an AIN‐93G diet with dried egg whites as the protein source and modified to increase oxidative stress (safflower oil instead of soybean oil and sucrose instead of dextrinized cornstarch) for 6 wk. Dietary variables were the basal diet containing (per kg) 1.5 mg Cu and 8 mg Zn, and basal diet supplemented (per kg) with 4.5 mg Cu, 10 mg Zn, or 4.5 mg Cu and 10 mg Zn. Two additional groups of 10 rats were fed the diets containing 18 mg Zn and 1.5 or 6 mg Cu per kg and pair‐fed with corresponding rats fed 8 mg Zn/kg diet. Cu‐def increased plasma extracellular superoxide dismutase and 8‐isoprostaglandin F2α (F2‐IsoP); the increases were amplified by pair feeding but not by Zn‐def. Zn‐def did not exacerbate the Cu def‐induced decrease in plasma ceruloplasmin. Zn‐def decreased urinary F2‐IsoP in Cu‐def but not Cu‐adequate rats, and decreased plasma RANKL in Cu‐adequate but not Cu‐def rats. The dietary treatments did not affect urinary nitrate. The findings indicate that a combined marginal Cu‐def and Zn‐def did not exacerbate, and even alleviated, some signs (RANKL and F2‐IsoP) of oxidative stress.
Carotenoid monooxygenase II knock‐out mice exhibit phenotypical differences and altered lycopene accumulation pattern compared to C57Bl6 mice
Authors: Ford Nikki A. , von Lintig Johannes , Wyss Adrian , Erdman John W.
Published: June 2021

Carotenoid monooxygenase II (CMO‐II) cleaves lycopene excentrically in vitro. Little is known about CMO‐II in vivo and therefore we evaluated feed intake, weight change, and lycopene accumulation in 11 male and 8 female CMO‐II knock‐out (CMO‐II KO) mice. Twenty‐three to twenty‐seven week old CMO‐II KO mice consumed a 10% tomato powder diet for 60 days and were compared to 27 week old C57Bl6 wild‐type mice. Twenty‐four hours prior to sacrifice, some mice were orally intubated with 3μCi of 14C‐lycopene in cottonseed oil. We verified successful loss of expression of CMO‐II by Real‐Time PCR. No differences in feed intake, weight, or health status were observed in CMO‐II KO mice compared to C57Bl6 wild‐type mice. Student's t‐test showed total lycopene concentration was higher in the adrenals (p=0.005) and uterus (p=0.02) of CMO‐II KO mice compared with wild‐type while no differences were found in the liver, seminal vesicles, or spleen. Organ weights were evaluated as a percentage of body weight. CMO‐II KO mice had significantly smaller livers (p=0.003), thymus (p=0.036), and seminal vesicles (p=0.034), but larger testes (p=0.0003). Preliminary evidence indicates CMO‐II KO mice have phenotypical differences from wild‐type mice and metabolize lycopene differently than wild‐type mice. (Funded in part by NIH grant PHS‐1‐RO1 CA125384.)
Effects of pumpkin seed extracted oil supplementation on benign prostatic hyperplasia patients
Authors: Hong Heeok , Kim Chun‐Soo , Kim Jung Yoon , Maeng Won Jai
Published: June 2021

This study was designed to investigate the effects of pumpkin seed extracted oil supplementation for 6 months on the treatment in benign prostatic hyperplasia (BPH) patients with average age 49.5 years old and total 33 BPH patients which were divided into two groups: placebo(sweet potato starch 320 mg/day, control) and pumpkin seed extracted oil (320 mg/day, PS group) supplementation. Measured parameters were international prostate symptom score (IPSS), quality of life (QoL), serum prostate specific antigen (PSA), prostate volume, maximum flow rate, serum total cholesterol, HDL‐cholesterol (HDL), LDL‐cholesterol (LDL), triglyceride (TG), and blood pressure. The IPSS, QoL, and PSA, measured after 3 and 6 months treatment decreased significantly in PS group as compared with pre‐experimental level, respectively(p<0.05). On the contrary, urine speed in all groups increased significantly after 6 months treatment (p<0.05). Diastolic and systolic blood pressure weren' t changed for all groups. All groups were kept normal criteria range during treatment period for total cholesterol, HDL, LDL and TG. According to the above results, pumpkin seed extracted oil supplementation is possible effectiveness of complementary for Korean men with BPH.
Puerarin and its glycosides do not show toxicity in vitro and in vivo.
Authors: Chung Hyuk jin , Chung Mi ja , Ham Seung‐Shi , Park Kwan Hwa , Lee Sung joon
Published: June 2021

Puerarin is an isoflavone derived from Kudzu roots and has antioxidant and hypocholesterolemic effects; however, its insolubility often limits its biological availability in vivo. Using a novel transglycosylation process, the solubility of puerarin glycosides was increased >100‐fold. High levels of puerarin and its glycosides might exert toxicity due to an estrogenic activity and other biological effects, thus, we investigated potential toxicity of puerarin and its glycosides. Mutagenic effects were investigated with Ames test and the results showed that both puerarin and its glycosides did not have dose‐dependent mutagenic effects. Antimutagenic properties of puerarin and its glycosides were tested with 4‐nitro‐quinoline‐1‐oxide as a mutagen. The results showed that the puerarin and its glycosides were able to significantly inhibit the mutations up to 50% of the controls. In addition, in vivo genotoxicity and cytotoxicity were examined by bone marrow micronucleus assay with ICR mice after oral administration of puerarin and its glycosides. Both puerarin and its glycosides did not reveal significant genotoxic and cytotoxic properties. Finally, Sprauge‐Dawley rats were orally administered with puerarin and its glycosides to investigate subchronic safety for 2 months. It was found that the administration of both puerarin and its glycosides did not significantly affect plasma and histological toxicity markers. These results suggest that puerarin and its glycosides do not have significant toxic effects both in vitro and in vivo, and may be safe as functional foods or other health related industrial applications.
Anti‐atherogenic effect of dandelion extracts through anti‐inflammatory and anti‐oxidative processes in C57BL/6 mice
Authors: Kim Jinju , Noh Kyunghee , Cho Mikyung , Jang Jihyun , Song Youngsun
Published: June 2021

Dandelion (Taraxacum officinale) a tranditional Oriental medicine, has been known to have anti‐atherogenic effects. However, the mechanism by which dandelion extracts protect against atherosclelosis is not clearly known. This study was designed to explore the effect of dandelion extract on inflammation and oxidative stress, risk factors of early atherosclerosis development. Five group of C57BL/6 mice were given atherogenic diet (control) or diets supplemented with 1.5%, 3% dandelion water extract (DWE I and II) and alcohol extract (DAE I and II) for 6 weeks. Supplementation of dandelion extracts did not affect body weight gain and food intake. sVCAM‐1 and MCP‐1 levels were decreased in dandelion supplemented groups and those levels are profoundly decreased in mice treated with DAE. The mRNA expression of MCP‐1 and VCAM‐1 were also down regulated, while the mRNA expression of eNOS was up regulated in aorta of dandelion supplemented groups than the control group. Hepatic TBARS was significantly decreased and GSH was elevated in dandelion supplemented groups. Furthermore, expressions of Cu/Zn SOD, Mn SOD and catalase were dose dependently up‐regulated in dandelion supplemented groups, while GSH reductase expression was up‐regulated at 1.5%, but down‐regulated at 3% supplementation level. SEM study showed that leukocyte adhesion and its subendothelial migration were more frequently observed in control group than dandelion supplemented groups. These data suggest that supplementation of dandelion extracts may ameliorate the development of atherosclerosis via the anti‐oxidative and anti‐inflammatory processes.
Dose response to antenatal corticosteroid (AC) exposure in rat offspring
Authors: Mikati Nadine , Church Michael W , Adams Brittany R , Jen K‐L. Catherine
Published: June 2021

The benefits of single course of AC treatment to pregnant woman with risk of preterm delivery are well‐established. However, repeated AC courses may impose harmful effects in offspring. The present study was designed to examine the relationship between different doses of AC on postnatal growth and brain morphology in rat offspring. Twenty‐four female Wistar rats were mated. The day when vaginal plugs were found was day 1 of pregnancy (P1). On P17, rats were randomly divided into 3 groups and received injections twice/day: Control (CON, n=6) with saline injections for 6 days; moderate (MOD, n=8) with 3 doses of betamethasone (BETA, 0.2 mg/kg) on P17–P19, saline on P20–P22; and high (HIGH, n=10) with 6 doses of BETA on P17–P22. Delivery occurred on P23–24. The birth weights of 3 groups were in the following order: CON>MOD>HIGH (p=0.08). One litter in CON group (16.7%), 1 in MOD (12.5%) and 2 in HIGH (20%) lost all pups within one week. At weaning, 16.7% of the CON, 37.5% of the MOD and 63.6% of the HIGH litters lost some or all pups. During the preweaning period, HIGH pups grew significantly slower than the CON pups (p<.01), even with fewer pups per litter, while MOD pup's weights were similar to the other 2 groups. Gross brain morphology revealed reduced myelination in the HIGH pups sacrificed at 24 days of age. Thus repeated AC not only impaired preweaning growth, but also affected brain development in offspring.
Activation of the liver x receptor (LXR) in utero does not affect lipid metabolism in mouse offspring upon high fat dietary challenge
Authors: Plosch Torsten , van Straten Esther M.E. , Huijkman Nicolette C.A. , Baller Juul F.W. , Kuipers Folkert
Published: June 2021

The Liver X Receptors LXRα/ß are vitally important in regulating cholesterol and fatty acid metabolism in the adult. Earlier studies by us have shown that prenatal exposure to a synthetic LXR agonist induces hyperlipidemia and hepatic steatosis in fetal mice. Aim of this study was to investigate effects of LXR activation in utero on lipid metabolism at a later age. Methods: Pregnant C57BL/6 mice were fed a diet containing the synthetic LXR agonist T0901317 from E10.5 until delivery. Pups were weaned onto chow. Pups received a high‐fat/high cholesterol (HFHC) diet or chow (C) from 6 till 8 weeks of age, after which hepatic gene expression and lipid levels were measured. Results: The HFHC diet led to 2‐ to 3‐fold increased hepatic triglyceride concentrations in male offspring. Plasma cholesterol concentrations were increased 1.6 times, while plasma triglyceride concentrations were unchanged. However, no differences between groups having received T0901317 or chow during gestation were observed. The HFHC diet led to induction of LXR target genes, but no effect of gestational T0901317 exposure was seen: expression of the cholesterol transporter Abcg8 was increased 2 times in both HFHC groups (with or without T0901317) whereas the expression of lipogenic genes Srebp1c and Scd1 were increased 2.5‐fold and 3‐fold, respectively in both HFHC groups. Conclusions: Fetal activation of LXR does not influence short‐term coping with a high‐fat/high cholesterol diet in young mice. Long‐term studies should elucidate whether fetal LXR activation exerts long‐lasting effects on the health of the offspring.

Supported by the Dutch Heart Foundation (2004T048).
Dietary supplementation with a nitric oxide donor to the diet for lactating sows enhances the growth of suckling piglets
Authors: Kim Sung Woo , Wu Guoyao
Published: June 2021

Diethylenetriamine‐NO adduct (DETA) is an effective NO donor which has a long half‐life in aqueous solutions. This study was to determine whether dietary DETA supplementation to lactating sows can increase their production performance and the growth of their nursing piglets. Nine primiparous sows with average litter size of 11.5±0.3 were assigned to 2 treatments: CON (without DETA, n=5) and DT (with DETA 50 mg/d, n=4) between d 7 and 21 of lactation. Sows had free access to feed and drinking water. Body weights and backfat thickness of sows, as well as body weights of piglets were measured at d 0, 7, 14, and 21 of lactation. Body weight loss during 21‐d lactation were 17.0 and 11.0 kg for CON and DT, respectively (P>0.05). Backfat losses of sows were 0.8 and 0.5 mm for CON and DT, respectively (P>0.05). However, litter weight gain of DT (40.5 kg) was greater (P<0.05) than CON (36.5 kg) during d 7 to 21 of lactation. Feed intakes of sows were 7.2 and 7.5 kg/d for CON and DT, respectively (P>0.05). Dietary DETA supplementation to lactating sows improved the growth of nursing pigs possibly by enhancing nutrient outputs in milk due to increased blood flow across the mammary gland.
Effect of total dietary fiber on satiety in dogs.
Authors: Yamka Ryan Michael , Friesen Kim
Published: June 2021

The objective of this study was to investigate the effects of feeding two foods with elevated levels of total dietary fiber on satiety in dogs. Both foods were formulated to contain similar levels of total dietary fiber (TDF; > 25% dry matter basis). The foods were fed to two groups of 10 beagles (average age = 4.64 ± 2.79 years; average weight = 14.0 ± 2.2 kg) for a period of 16 weeks in order to determine the effect of total dietary fiber on satiety. During the study dogs were given ad libitum access to the foods for a period of 45 minutes. Food intake was recorded daily and body weight was recorded weekly to determine the effects of fiber on satiety and weight maintenance. During the 16 week study, body weight decreased (1.4 kg on average; P < 0.01) on both treatments while intake increased (82 g on average; P < 0.01). There were no differences between the two treatments for intake or body weight at week 1 or 16 indicating that the level of TDF in the food was efficacious in promoting satiety in beagles. Interestingly, dogs only lost weight during weeks 1 to 4 and then maintained body weight thereafter (weeks 4 to 16). The results of this study demonstrate that satiety and body weight can be controlled in beagles fed ad libitum with foods containing > 25% total dietary fiber.
Defibrotide Interactions with Anticoagulant Drugs. Developmental Implications.
Authors: Hoppensteadt Debra , Cunanan Josephine , Clark Melanie , Iqbal Omer , Adiguzel Cafer , Fareed Daniel , Fareed Jawed
Published: June 2021

Defibrotide (D) is a mammalian polyelectrolyte/polyribonucleotide derived antithrombin agent with aptameric consensus antithrombin sequences. This agent is used in vascular system in both the intravenous and oral regimens. Since this drug is used in certain pathologic conditions where other anticoagulants such as heparin (H), low molecular weight heparins (LMWHs) and oral anticoagulants (OAC) are used, the potential interaction of this agent with these drugs needed an understanding of these processes. In order to investigate the potential interaction between D, H and OAC, plasma samples from patients treated with H at therapeutic dosages (n=100), (APTT=50–90 seconds): LMWHs (n=100), (Heptest= 60–90 seconds); and OAC (n=100), (PT= 18–25 seconds) were supplemented with graded dosages of D, 10–100 ug/ml. H showed a D concentration dependent synergistic interaction in terms of a 20–80% increase in the APTT, whereas this interaction was not sp obvious with Heptest and anti‐Xa. LMWHs at concentrations >0.3 U/ml also showed an interaction with D, however to a lesser magnitude that H. D did not show any strong interaction with OAC in terms of PT/INR measurements. In the thrombin generation assays D supplementation augmented the inhibition of protease generation. These results suggest that D can potentially interact with currently available anticoagulant drugs. Moreover, the interaction of this agent with newly developed antithrombin and anti‐Xa agents warrants additional studies.
Differential Prevalence of Anti‐Heparin PF4 Immunoglobulin Subtypes in Patients Treated with Reviparin, Enoxaparin, and Certoparin. Implications in HIT Pathogenesis.
Authors: Fareed Jawed , Hoppensteadt Debra , Ahmad Sarfraz , Walenga Jeanine , Cunanan Josephine , Bick Rodger , Saxena Renu
Published: June 2021

Heparin and low molecular weight heparin (LMWHs) represent complex mixtures of sulfomucopolysaccharides with structural and functional heterogeneity. Therefore, there interactions with endogenous binding proteins such as platelet factor 4 (PF4) differ leading to differential neutralization and immunogenic responses. In order to demonstrate the difference in immunogenic responses in plasma samples from patients treated in three different clinical trials, namely ECHOS (Reviparin, 4200 anti‐Xa U/o.d., s.c. for 11–14 days) for post‐orthopedic prophylaxis; OCENOX (enoxaparin, 1.0 mg/kg s.c. bid for up to 3 months) for treatment of deep vein thrombosis in cancer patients and PARAT (Certoparin, 1mg/kg s.c.,o.d. for up to 3 months) for post PTCA restenosis were retrospectively analyzed for the presence of anti‐heparin – PF4 antibodies and there subtypes using an ELISA method (GTI, Brookfield, WI). The antibody titers and subtypes were compared in samples collected at 10–14 days. Of the 100 samples analyzed in each of these groups, the prevalence of ELISA positive antibodies differed, Reviparin (12.5%), Enoxaparin (15.2%) and Certoparin (18.1%). None of these sera produced 14C serotonin release. The subtyping of these antibodies in terms of IgG, IgA and IgM, also exhibited different profiles with predominant IgA and IgM subtypes. Certoparin exhibited relatively higher IgG subtypes. These studies demonstrated that the immunogenic potential of different LMWHs vary widely in terms of the antibody titer and subtypes.
Vascular Leak in Melanoma is Triggered by VEGF and Other Secreted Factors
Authors: Kluger Martin S. , Weng Shaojie
Published: June 2021

Because leaky blood vessels promote melanoma progression and blockade of VEGF‐A by Avastin (bevacizumab; FDA‐approved anti‐VEGF‐A) is only partially effective, we have developed new models for studying the endothelial cell (EC) response to YUSIT, a human melanoma cell line. Human dermal microvascular EC (HDMEC) forming leak‐resistant monolayers on transwells reduced transendothelial electrical resistance (TEER) by 50% at 24 h when co‐cultured with YUSIT, suggesting YUSIT secrete leak‐inducing factors. Indeed, YUSIT conditioned medium contains VEGF‐A (6 ng/ml) and incubation with HDMEC decreased TEER 40–50% by 4 h. Although this response was inhibitable by Avastin, TEER was partially decreased even by conditioned medium depleted of VEGF. Adding back a small amount of VEGF (0.2 ng/ml) to VEGF‐depleted conditioned medium decreased TEER more effectively than a 100‐fold greater VEGF concentration in fresh medium, suggesting YUSIT secrete additional leak factors. YUSIT injected s.c. formed leaky tumors in human skin grafted onto immunodeficient SCID mice and conditioned medium elicited vascular leak as well as high concentration VEGF; depleting conditioned medium of VEGF removed most of the in vivo leak activity. We conclude melanoma VEGF and other secreted factors trigger vascular leak and that these new models can be used for understanding how human EC contribute to melanoma progression. Supported by NCI.