bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Habits and Degree of Satisfaction with Meal Service by Students with Visual Impairment
Authors: Chung Hyun-Jung , Park Hyun-Jung
Published: June 2021

The purpose of this study was to provide basic data, to establish desirable dietary habits, and to give instructions for students with visual impairment. Over two hundred middle and high school students (137 boys and 107 girls) with visual impairment in Seoul, Gyeonggi Province and Incheon, were surveyed for interest in nutrients, dietary habits, taste for meal service and satisfaction with meal service. As for the general information of the subjects, many of them had low vision and lost sight in a postnatal manner. They showed huge interest in nutrients and obtained the most information about nutrition from the mass media and meal service. Students had meals regularly, yet showed irregular breakfast patterns. They held the right posture during eating, did not spill food, and were good at using a spoon and chopsticks. The biggest factor to affect their dietary habits was the family's dietary habits, which were followed by their homeroom teachers. As for the dietary habits to be improved and picky eating habits, many students were trying to correct their picky eating habits and demonstrated willingness to improve their picky eating habits. However, many students showed no interest in picky eating, suggesting that they need some education to choose variety of foods. In short, the schools should provide students with visual impairment with education to teach the importance of desirable dietary habits through the meal service, balanced nutrition for the menus of the lowest preference, and menus fit for their preference. In addition, they need to develop programs and education materials to provide nutrition counseling and education to help them with their picky eating habits and improper dietary habits due to multiple disabilities, diseases, long‐term intake of medication, and family environments.

Grant Funding Source: Inha University
Insulin‐Independent Mechanisms of Action of Pre‐Meal Consumption of Whey Protein on Post‐meal Glycemic Response in Healthy Adults
Authors: Akhavan Tina , Luhovyy Bohdan L. , Brown Peter H. , Anderson G. Harvey
Published: June 2021

Whey protein (WP) when consumed prior to a meal reduces post‐meal glycemic response (Akhavan et al, AJCN, 2010). The objective of the study was to identify insulin‐independent mechanisms of action. Healthy men received, in a randomized order, WP and glucose preloads (10 and 20 g/300 mL) and water control with paracetamol (1.5 g). At 30 min after consumption, the subjects were fed a preset pizza meal (12 kcal/ kg). Plasma concentrations of paracetamol, glucose and incretin hormones, involved in glycemic control, were measured at pre‐ (0–30) and post‐ (50–230 min) meal. Pre‐meal plasma paracetamol concentrations were reduced by WP, indicating delayed gastric emptying. Consumption of WP and glucose similarly reduced post‐meal plasma glucose but insulin was increased only after glucose preloads (p < 0.001). Associated with the lower post‐meal glycemic responses after WP were lower C‐peptide and higher GLP‐1, PYY and ghrelin (all p < 0.001), but similar amylin and GIP than after glucose preloads. These responses support the hypothesis the glycemic control after WP occurs in part by noninsulin dependent mechanisms. Thus, pre‐meal consumption of WP may be a novel strategy, comparable to pharmacological therapy e.g. sulphonylureas, for the prevention and treatment of hyperglycemia and type 2 diabetes.

Grant Funding Source : Supported by Natural Sciences and Engineering Research Council of Canada‐Collaborative Research and Development and Kraft Canada Inc
Isoleucine requirement for pregnancy in adult sows
Authors: Moehn Soenke , Franco Danilo J , Josephson Jessica K , Pencharz Paul B , Ball Ron O
Published: June 2021

Pregnant adult sows show little maternal growth so that accelerated conceptus growth in the 3rd trimester can cause large differences in nutrient requirements between early (EG) and late (LG) gestation. The objective of this study was to determine the Ile requirement in EG (d 37 to 61) and LG (d 89 to 109) using the indicator amino acid oxidation (IAAO) method. Seven 4th parity sows received 6 diets each based on corn, corn starch and sugar in both EG and LG at a constant intake of 2.5 kg/d. Diets in EG contained Ile at 20, 40, 60, 80, 100 and 120 % of the current Ile requirement and 60, 80, 100, 140, 160 and 180% in LG. Sows were fed 2 mg/(kg BW•h) of L[1‐13C]Phe over 4 h in 8 ½‐hourly meals. Requirements were determined as breakpoints in IAAO using 2‐phase nonlinear models. Sows, 232.0 ±4.9 kg at breeding, gained 19.1 ±4.4 kg in gestation and had litters of 17.7 ±0.75 piglets weighing 22.6 ±0.87 kg. The Ile requirement was greater in LG than EG (P = 0.001) at 3.6 g/d vs. 9.7 g/d. The increase (P = 0.001) in Phe retention (−0.48 ±0.55 g/d in EG vs. 3.34 ±0.55 g/d in LG) was caused by accelerated fetal growth. Energy and lipid retention decreased (P < 0.003) from EG to LG and were negative in LG. This indicates that Ile requirements were driven mainly by maintenance in EG and by fetal growth in LG. Both Ile and energy intake must be increased in LG but the greater change in Ile than energy requirement shows that amino acid supply is more critical in LG for adult sows.
Rab2 plays a role in lipid metabolism in the intestine
Authors: Chung Bomee , Schürmann Annette
Published: June 2021

Intestinal lipid metabolism is comprised of multi‐steps of vesicle trafficking. Rab2 is localized in pre‐Golgi intermediates and required for vesicle trafficking between the endoplasmic reticulum and the Golgi. The aim of the study was to investigate the role of Rab2 in the secretion of chylomicron in the intestine. Rab2 expression was suppressed by transfection of specific siRNA in Caco‐2 cells, an intestinal in vitro model, and lipid absorption and lipoprotein production were examined. Rab2 expression was efficiently depleted by siRNA transfection for 14 days without interrupting cell differentiation. Apolipoprotein (Apo) B100 secretion was significantly lower in Rab2 siRNA transfected cells in the basal condition, but it recovered when the cells were oil‐loaded. In the same way, triglyceride secretion was slightly decreased in the basal condition, but recovered by oil‐load. Expression of microsomal triglyceride transport protein (MTTP) was not affected by Rab2 disruption. Rab6 expression was significantly increased in Rab2 siRNA transfected cells. These data suggest that Rab2 and Rab6 are involved in chylomicron secretion in Caco‐2 cells, and compensate its role each other.

Grant Funding Source : Alexander von Humboldt Foundation
Relationships between concentrations of arachidonic and docosahexaenoic acids in cord blood and placental polychlorinated dibenzo‐p‐dioxins (PCDD), dibenzofurans (PCDF), and polychlorinated biphenyls (PCB) at delivery
Authors: SU YU TING , SUN PEI-YI , WANG SHU-LI , HUANG MENGCHUAN
Published: June 2021

Long chain polyunsaturated fatty acids (LCPUFA), ARA and DHA have positive effects, and environmental toxins, polychlorinated dibenzo‐p‐dioxins/dibenzofurans (PCDD/F) and polychlorinated biphenyls (PCB) have negative effects on perinatal development. Previous studies showed that placental toxic equivalent (TEQ) levels of PCDD/F and PCB correlated significantly with those of maternal blood, human milk, and cord blood in Taiwanese women, thus placental levels are considered indicators as perinatal accumulative exposure of dioxin and PCB (Chemosphere 54 (2004) 1459–1473). This study aimed to investigate correlations between cord blood concentrations of ARA/DHA with placental TEQ of PCDD/F and PCB in 31 pregnant women from Taiwan. Concentrations of ARA(wt%) in cord blood did not associate with placental TEQ of PCDD/F and indicator/dioxin‐like PCB(p=0.602–0.735). Cord blood DHA(wt%) also did not show correlations with PCDD (p=0.097), PCDF (p=0.219), indicator PCB (p=0.108) or dioxin‐like PCB (p=0.055). Future study will be directed to investigate relationships among food consumption and LCPUFA/dioxin/PCB levels in various peinatal biospecimens in a more representative sample size.
Metabolomics‐based investigation of cocaine‐induced disruption of lipid metabolism
Authors: Shi Xiaolei , Yao Dan , Wang Lei , Chen Chi
Published: June 2021

Besides its psychological and behavioral effects, cocaine can also cause liver injury. Lipid accumulation in the liver is a pathological change occurred prior to cell death. However, the specific effects of cocaine on the homeostasis of lipid metabolism remain largely unknown. In this study, we conduct metabolomic analysis of serum samples from control and cocaine‐treated mice, along with histological and biochemical analyses. During 3‐day cocaine injection, hepatocytes in pericentral vein zone underwent progressive impairment. Serum transaminase activity was elevated dramatically at the 2nd day of cocaine treatment while the increase of both serum and hepatic triglyceride levels occurred at the 1st day of cocaine injection, suggesting the disruption of lipid metabolism preceded cell death in cocaine‐induced hepatotoxicity. LC‐MS‐based metabolomic analysis revealed that the accumulation of long‐chain acylcarnitines in serum, together with the imbalance between phosphotidylethanolamine and phosphatidylcholine species, contributes to the time‐dependent separation of control and cocaine‐treated mice in a multivariate model. Pretreatment of fenofibrate, an agonist of transcriptional factor PPARα that regulate fatty acid oxidation, completely reversed the increases of acylcarnitine level and transaminase activity and abolished cocaine‐induced cell death, suggesting that the inhibition of fatty acid oxidation plays an important role in the cocaine‐induced liver injury. Overall, our metabolomic investigation detected the unreported metabolic events elicited by cocaine exposure and provided novel insights on the underlying mechanism of these events.

Grant Funding Source : NIH
Elongase of long chain fatty acids family 6 (ELOVL6) and stearoyl‐CoA desaturase ‐1 (SCD1) indices suggests potential metabolic benefits in patients with a range of liver fat contents
Authors: Lee Joseph J , Bradford Dora L , Valdez Maressa J , Hovhannisyan Yelena , Lambert Jennifer E , Ramos-Roman Maria A , Parks Elizabeth J
Published: June 2021

SCD1 and ELOVL6 enzyme activities and dietary fatty acid composition contribute to the balance of monounsaturated (MUFA), polyunsaturated (PUFA), and saturated fatty acids (SFA) in the plasma free fatty acid (FFA) pool. Given the potential lipotoxic effects of SFA, the present study investigated FFA composition in fasted and meal‐fed (42g fat, 100g carbohydrate) nondiabetic, African American and Hispanic adults (n = 14, BMI 35.6 ± 6.8 kg/m2, 47.7 ± 8.5 yrs) with low (< 5.6%) or high (> 5.6%) liver fat. FFA composition (mol %) was determined by GC, substrate oxidation by indirect calorimetry, and substrate metabolism using stable isotopes. Low ELOVL6 index (18:0/16:0) was associated with high postprandial insulin (r = − 0.622, P = 0.02) and lower in those with high liver fat (P = 0.01). Fasting FFA turnover correlated with FFA 18:1n9 (r = +0.694, P = 0.01) and 18:2n6 (r = +0.642, P = 0.01), and negatively with 18:0 (r = −0.731, P < 0.01) and 16:0 (r = −0.731, P < 0.01). Whole body fat oxidation correlated with 16:1n7 (r = +0.646, P = 0.02) and indices of SCD1 including 18:1n9/18:0 ratio (r = +0.558, P < 0.05) and 16:1n7/16:0 (r = +0.633, P = 0.02). Fat oxidation correlated inversely with 18:0 (r = −0.592, P = 0.03). Thus, 18:1n9 may be a biomarker for both greater FFA turnover and disposal. These data support beneficial effects of MUFA over SFA in overweight subjects and a positive influence of ELOVL6 and SCD1 on insulin sensitivity and liver fat.
Ground beef consumption and MUFA:SAT alters HDL oxylipin profile in healthy men
Authors: Wu Xiuzhi , Smith Stephen B. , Crouse Stephen F. , Pedersen Theresa L. , Newman John W. , Walzem Rosemary L.
Published: June 2021

Omega‐6 fatty acids from red meat have been associated with increased inflammatory disease risk via the production of pro‐inflammatory lipid mediators. Oxylipins are oxygenated polyunsaturated fatty acids (PUFAs) that play important roles in vascular homeostasis and inflammatory responses. This study aimed to compare the effects of MUFA:SAT in ground beef patties with a fixed total fat content of 24 g fat/100 g patty on HDL oxylipin profile in 25 healthy men. Test beef patty MUFA:SAT was either 1.10 (HI) or 0.71 (LO). Subjects consumed 5 patties per week in a random test‐retest design lasting 5 weeks each separated by 4‐week wash‐out period. Results showed that independent of MUFA:SAT, beef consumption altered HDL oxylipin composition by decreasing the pro‐inflammatory 5‐oxo‐eicosatetraenoic acid (5‐KETE) (p<0.05). A greater reduction occurred in subjects of lower HDL n3:n6 fatty acid ratio (p=0.05). HI MUFA beef consumption significantly increased the total fractional abundance of oxylipins derived from DHA (p<0.05), and decreased total diol and ketone concentration (p<0.05). Our study shows that HDL oxyplin profile may be improved by beef consumption per se, as judged by the decreased oxidative stress indicator 5‐KETE, and that beef with a HI MUFA:SAT may cause further improvements. “Funded in part by The Beef Checkoff through the National Cattlemen's Beef Association”
CONJUGATED LINOLEIC ACID‐INDUCED LIPOLYSIS IN 3T3‐L1 ADIPOCYTES
Authors: Ippagunta Siri M , Barnes Kimberly M
Published: June 2021

Conjugated linoleic acid (CLA) has caused an inconsistent increase in lipolysis in cell culture studies. The objective of this study was to determine the optimum dose, time, and serum conditions for CLA‐induced lipolysis in 3T3‐L1 cells. 3T3‐L1 cells were differentiated and serum starved overnight before pre‐loading with 3‐[H] oleic acid for 12 hrs. Cells were then treated with CLA or linoleic acid (LA) at different doses and times. Lipolysis was measured as the 3 hr release of 3‐[H] oleic acid with 0 (basal) or 10 (stimulated) μM isoproterenol. For the dose curve, cells were treated with 20, 30, 50, or 75 μM CLA or LA for 12 hrs. CLA increased basal lipolysis (P < 0.0001) compared to LA at 30, 50, and 75 μM, with the greatest difference at 50 μM. For the time course, cells were treated with 50 μM CLA or LA for 6, 12, 24, or 36 hrs. CLA increased lipolysis (P<0.0001), compared to LA at 12 and 24 hr, with maximal lipolysis occurring at 12 hrs (P<0.0001). For the effect of serum, cells were either serum‐starved or treated with delipidated or whole serum prior to treatment with 50 μM CLA for 12 hrs. Serum‐starved cells had increased lipolysis (P<0.0001) compared to cells treated with delipidated or whole serum. CLA caused an increase in lipolysis (P < 0.05) only in serum‐starved cells. CLA‐induced lipolysis in 3T3‐L1 cells is most optimal at a dose of 50 μM and at a treatment period of 12hrs when cells are serum‐starved prior to treatment with CLA.

Grant Funding Source: HATCH
Effect of plant sterol esters on cardiovascular risk factors in hypercholesterolemic adults
Authors: Sauder Katherine A , Psota Tricia L , Kris-Etherton Penny M , Bagshaw Deborah , Alaupovic Peter , West Sheila G
Published: June 2021

Daily consumption of plant sterol esters has been shown to decrease total and LDL cholesterol. We examined whether delivery of plant sterol esters in a low‐fat dairy dessert could decrease cardiovascular risk factors. We enrolled 49 hypercholesterolemic adults in a randomized, double‐blind, crossover study with 4‐week control and treatment periods. Participants consumed two 68g portions of the dessert daily, providing 2 g/d free plant sterols, and were counselled to follow the Therapeutic Lifestyle Changes diet. Lipids, apolipoproteins, cellular adhesion molecules (CAM), inflammatory markers, blood pressure, and cardiovascular reactivity to stress were assessed at baseline and after each treatment period. Total and LDL cholesterol decreased more after consumption of the plant sterol dessert compared to placebo (−6.0% vs −2.4% and −8.3% vs −2.7%, respectively, p<0.0001). Apolipoprotein A‐I increased after the plant sterol dessert (p<0.05). No significant changes were observed between treatments for HDL, triglycerides, CAM, and inflammatory markers. Blood pressure and total peripheral resistance during stress were lower following the placebo dessert compared to the plant sterol dessert (p<0.05). These results demonstrate that delivering 2 g/d of free plant sterols through a low‐fat dairy dessert for four weeks is clinically effective in reducing total and LDL cholesterol.

Funding: Unilever
Dietary lipids and its effect on lipids profile in serum of growing rats
Authors: Perris Paula , Fernandez Inés , Mambrin Cecilia , Slobodianik Nora , Feliu Susana
Published: June 2021

The objective is to analyze the effect of high fat diets on triglycerides (TG), total cholesterol (TC), HDL cholesterol and fatty acid profile of growing rats. Weanling Wistar rats were fed during 10 days: 50% dietary fat provided by butter and cocoa butter (S group); 50% dietary fat provided by olive oil and soy oil (M group). Control group(C) received normocaloric diet.

Fatty acid profiles were determined by gas chromatography (GC); ω3/ω6 and unsaturated/saturated (UFA/SFA) ratios of diets were calculated. Serum levels of TG, TC and HDL were determined by enzymatic‐colorimetric method and fatty acid profile, was determined by GC (area %).

Results

ω6/ω3 diets ratio: S = 8.7 / 1; OS = 15 / 1; C = 9 / 1; UFA/SFA, S = 0.54; OS = 4.2; C = 5.5. Serum (mean±SD mg/dL) TG S: 191.9±66.5; M: 98.1±49.7 ;C: 94.1±37.7; CT S: 83.8±10.9 M: 78.2±10.5 C: 81.1±14.8; HDL S: 32.9±11 M: 36.8±9.0 C: 32.9±9.5. TG levels in S were statistically higher compared to C and M (p<0.01).

Serum oleic acid levels in S and M groups were higher than C (S = 20.49 ± 2.41, OS = 20.95 ± 5.14, ± 3.41 C = 11.43, p <0.01).

The S diet induces high levels of TG, as a result of the type of fatty acids received more than to the high concentration of lipids. The administration of diets probably caused changes in serum levels of oleic acid in response to differences in the profile of fatty acids of the sources used and the provided percentage of fat, which would exacerbate the route of the ω9 family.
Omega‐6 to omega‐3 fatty acid ratio and higher‐order cognitive functions in 7‐to‐9‐year‐olds
Authors: Will Kelly , Cheatham Carol L , Stegall Julie
Published: June 2021

This study's objective was to investigate the importance of the omega‐6/omega‐3 fatty acid ratio to higher‐order cognitive functions in early school‐age children. Omega‐6(n‐6) and omega‐ 3(n‐3) fatty acids are found in abundance in the human brain, and n‐3 fatty acids have long been thought to be important for cognitive function. However, n‐6 fatty acids work with n‐3 fatty acids for functions such as synaptic transmission and synaptogenesis. Moreover, n‐6 and n‐3 fatty acids compete for metabolic resources. The n‐6/n‐3 ratio is a better measure for understanding the importance of fatty acids for optimal cognitive functioning. We hypothesized that children with a lower n‐6/n‐3 ratio would perform better on cognitive function tests than children with a higher ratio. Children ages 7 to 9 provided three days of diet recalls and their parents completed a Diet History Questionnaire. The participants then completed a series of standardized cognitive function tests using CANTAB software. The n‐6/n‐3 ratio was a significant predictor of processing speed in solving harder working memory, F(11,51)=2.08, p=.039, and planning problems, F(11,45)=2.24, p=.029. n‐6 and n‐3 fatty acids alone were not significant predictors of any cognitive function measures. These results suggest that the n‐6/n‐3 ratio is a better tool for understanding the importance of fatty acids to cognitive functions than n‐6 or n‐3 fatty acids alone. This research was supported by a pilot grant # 2KR221004 from the North Carolina Translational and Clinical Science (TraCS) Institute and the Cheatham Nutrition & Cognition Lab.
Antioxidant and skin pores contraction activity of Malus domestica Borkh
Authors: Son Da-Hee , Nam Mi-Hyun , Hong Chung-Oui , Chun Su-Hyun , Kim Young-Bu , Lee Kwang-Won
Published: June 2021

Green apple is important not only for its high antioxidant contents, but also for its acceptance among the general consumer. The aim of this study is to confirm the effect of green apple extracts on skin pores contraction through antioxidant activity, quantification of tannin contents, protein aggregation assay and inhibition of 5‐alpha‐reductase type 1 mRNA expression. First, Green apple was separated to whole apple, apple rind, pulp, seed and each group was extracted with 70% ethanol. Apple rind exhibited significantly higher antioxidant activity, tannin contents. So, apple rind was fractionated with hexane, CHCl3, EtOAc, BuOH and water to get active fraction. Among these solvent fractions, green apple rind ethyl acetate (AR‐E) has a greatest antioxidant activity and tannin content. Also, protein aggregation of green apple fraction has an effect as compared with positive control tannic acid. The major factor contributing to excess sebum is 5‐alpha reductase type1 which related to enlarge skin pores. We confirmed that green apple fraction reduced 5‐alpha reductase type1 expression in HaCaT using RT‐PCR method. In conclusion, we expected the beneficial effect of green apple on skin pores contraction

Grant Funding Source : Ipeeres Ltd.
Antioxidant and skin pores contraction activity of Vaccinium corymbosum
Authors: Son Da-Hee , Nam Mi-Hyun , Hong Chung-Oui , Chun Su-Hyun , Lee Sun-Young , Lee Kwang-Won
Published: June 2021

Blueberry has attracted much attention due to their potential health benefits. Blueberry contains a diverse of biological properties such as antioxidant and anti‐inflammatory activities. The aim of this study is to confirm the effect of blueberry extracts on skin pores contraction through antioxidant activity, quantification of tannin contents, protein aggregation assay and inhibition of 5‐alpha‐reductase type 1 mRNA expression. Blueberry was extracted with 70% ethanol and then fractionated with hexane, CHCl3, EtOAc, BuOH and water to get active fractions. Antioxidant activity of each fraction was determined by using the DPPH and FRAP assay. All fractions had high antioxidant activities, tannin contents than crude extract, but blueberry ethyl acetate (BB‐E) fraction was at the top of the list. Protein aggregation of blueberry fraction has an effect as compared with positive control tannic acid. The major factor contributing to excess sebum is 5‐alpha reductase type1 which related to enlarge skin pores. We confirmed that blueberry fractions reduced 5‐alpha reductase type1 expression in HaCaT using RT‐PCR method. In conclusion, we expected the beneficial effect of blueberry on skin pores contraction.

Grant Funding Source : Ipeeres Ltd.
White common beans (Phaseolus vulgaris) have higher in vitro iron bioavailability than colored seed coat varieties
Authors: Mutambuka Martin , Murphy Patricia , Hendrich Suzanne , Reddy Manju B.
Published: June 2021

The common bean is an important source of iron in developing countries and there is need to improve their iron bioavailability. This study aimed at screening 21 bean varieties (16 varieties from Uganda and 5 from Columbia) for iron bioavailability with an overall objective of modeling it with respect to key influencing factors; protein, polyphenol, phytate, bean ferritin and iron content. A Caco‐2 cell culture model was used to determine iron uptake from in vitro digested bean samples. Protein content ranged from 25.7–31.6 %; polyphenols, 0.07–0.37 mg/100g; phytates, 0.91–2.17 g/100g; iron, 128.5–154.5 μg/g; bean ferritin, 206–497 μg/g, and relative iron bioavailability (based on 100% bioavailability of ferrous sulfate) was 9.1–52.1%. The two white bean varieties had the highest bioavailability (38–52%) and were significantly different from colored seed coat varieties (9–18%). A fixed effects multiple regression model showed negative effects of polyphenols and phytates and positive effects of iron content. In conclusion, iron bioavailability in common beans is influenced by iron, polyphenol and phytate contents.

Source of support: US‐AID under the Dry Grain Pulses CRSP
Impact of iron‐contained micronutrient supplementation on macrosomia and large for gestational age births
Authors: Liu Jian-meng , Mei Zuguo , Ye Rongwei , Serdula Mary , Li Hong-tian , Cogswell Mary
Published: June 2021

Objective

We aimed to assess the impact of prenatal iron‐contained micronutrient supplementation on macrosomia or large for gestational age (LGA) births in a relatively wealthier area of China.

Methods

We conducted a randomized controlled trial among nulliparous pregnant women. Women were enrolled before 20 weeks gestation and randomized to receive daily folic acid (FA), iron + folic acid (IFA), or iron, folic acid, + 13 other micronutrients (MN). Outcomes were macrosomia and LGA. In main analyses, we calculated relative risks (RRs) of macrosomia or LGA for IFA and MN versus FA. In subgroup analyses, we used logistic regression with interaction terms to adjust for covariates and assess modification effect of maternal baseline BMI (<25/≥25kg/m2).

Results

Of 18775 women randomized, 17738 delivered singleton live births. Baseline characteristics and adherence did not differ by groups. Prevalence of macrosomia and LGA were 4.3% and 22.9%. Compared to FA, the RR (95% CI) of macrosomia was 1.04 (0.87, 1.23) for IFA and 1.08 (0.91, 1.28) for MN; corresponding RR of LGA was 1.01 (0.95, 1.08) and 0.99 (0.93, 1.06). In multivariable analyses, odds ratios were not varied by maternal BMI (P values for interaction >0.19).

Conclusion

Compared with FA, IFA or MN supplementation did not increase the risk of macrosomia or LGA in this well nourished population.

The study is funded by a cooperative agreement between PUHSC and CDC.

Grant Funding Source : Centers for Disease Control and Prevention
Kaempferol ameliorates airway inflammation through Tyk2‐STAT1/3 signaling in human airway epithelial cells and ovalbumin‐challenged mice: role of interleukin‐8
Authors: Gong Ju Hyun , Kang Young-Hee
Published: June 2021

Allergic asthma is characterized by bronchial airway inflammation resulting in increased airway hyperresponsiveness, eosinophilia and mucus hyperproduction. The interaction between the airway epithelium and inflammatory mediators plays a key role in the pathogenesis of allergic asthma. The in vitro study elucidated inhibitory effects of kaempferol, a flavonoid with anti‐inflammatory activity, on LPS or IL‐8‐induced airway inflammation in BEAS‐2B cells. Nontoxic kaempferol at ≤20 μM significantly inhibited the LPS‐induced IL‐8 production through the TLR4 activation, resulting in eotaxin‐1 induction. In addition, kaempferol attenuated Tyk2 phosphorylation and STAT1/3 activation following IL‐8 secretion by LPS, and further enhanced the Tyk activation‐inhibiting SOCS3 expression. The in vivo study explored demoting effects of kaempferol on asthmatic responses in BALB/c mice sensitized with ovalbumin (OVA). Oral administration of kaempferol suppressed goblet cell hyperplasia, collagen deposition and mucus secretion in the airway and lung of OVA‐challenged mice via a blockade of STAT3 transactivation. These results demonstrate that dietary kaempferol alleviated airway asthmatic remodeling through modulating Tyk‐STAT signaling responsive to the inflammatory chemokine IL‐8. Therefore, kaempferol may be a potential therapeutic agent targeting inflammatory airway diseases such as asthma.
Population dynamics of leukocytes in blood during early activation of the chicken immune system by E. coli
Authors: Iseri Vanessa J. , Klasing Kirk C.
Published: June 2021

The immune system must have appropriate levels of nutrients to support changes in leukocyte numbers during immune response, but quantitative aspects are poorly characterized. Thus, examined the early time course of peripheral blood leukocytes of adult Hyline chickens injected IV with dead E. coli. After primary injection, blood was collected and total white blood cells (WBC), CD4+, CD8+), IgM+, IgG+), and macrophage/monocyte numbers were determined. WBCs decreased at 4hr, 18hr, 24hr, and 48hr post‐injection (PI) compared to baseline (P<0.0001 for first 3, P=0.04). CD4+ decreased compared to baseline at 4hr, 18hr, 24hr, and 48hr PI (P<0.0001 for first 3, P=0.01). CD8+ decreased compared to baseline at 4hr, 18hr, 24hr, and 48hr PI (P<0.0001 for first 3, P=0.0001). IgM+ decreased compared to baseline at 4hr, 18hr, 24hr, and 48hr PI (P<0.001 for first 3, P=0.004). IgG+ decreased at 4hr, 18hr, 24hr, and 48hr PI compared to baseline (P<0.0001 for first 3, P=0.0009). Macrophage/monocytes decreased at 4hr, 18hr, 24hr, and 48hr PI compared to baseline (P=0.0008, P=0.003, P=0.008, P=0.01). Maximal percent decrease in cell numbers at 4hr for WBC was 96%. Decrease of cellular components in blood occurred, observed an increase in cell number in spleen, thymus and bone marrow. Converted to a whole body basis, the 70% decrease is less than the changes observed in other tissues indicating a decrease in nutrient use due to activation.

Grant Funding Source: USDA Regional Research project 1013
Dietary Gangliosides Improve Intestinal Integrity and Function by Decreasing sPLA2 Independent NF‐kB Activation Mechanism in a Caco‐2 Cell Model of IBD by DSS
Authors: Li Qun , Thomsom Alan B.R. , Mazurak Vera C. , Field Catherine J. , Clandinin M. Tom
Published: June 2021

Gangliosides are negatively charged glycosphingolipids that consist of a hydrophobic ceramide and a hydrophilic oligosaccharide chain bearing one or more sialic acid. Both animal and human cell studies suggest that gangliosides have anti‐inflammatory effects by modulating cytokine expression. The objective of this study was to use Caco‐2 IBD model induced by dextran sulfate sodium to investigate benefits of ganglioside supplementation on IBD signaling mechanisms. Epithelial barrier function was examined by measuring TEER and intestinal morphological structure damage was studied via TEM. HBD‐2, sPLA2 and NF‐kB was determined by ELISA methods. Results indicated that supplementary ganglioside significantly decreased inflammatory HBD‐2 level, improved the defective epithelial barrier function and protected the disruption of intestinal junction complexes. The sPLA2 level in the basolateral medium was significantly decreased in ganglioside supplemented cells by 40%. NF‐kB P65 activation was significantly increased by DSS alone or with ganglioside supplement. In conclusion, the present study indicated that ganglioside has promising beneficial effects on IBD by decreasing inflammatory signaling, improving epithelial barrier function and protecting intestinal integrity. The anti‐inflammatory effect may also partly contribute to decrease of sPLA2 level, while independent of NF‐kB activation.

Grant Funding Source : CIHR
Porcine milk fat globule membrane proteins that bind to F4ac fimbria of Escherichia coli
Authors: Novakovic Predrag , Huang Yanyun , Charavaryamath Chandrashekhar , Lockerbie Betty , Kelly John , Loewen Matthew E. , Simko Elemir
Published: June 2021

Post‐weaning colibacillosis in pigs is caused by enterotoxigenic Escherichia coli (ETEC) which is often controlled by antibiotic feed supplements with potential risk of generation of antibiotic resistant bacteria. Prevention of attachment of F4ac+ ETEC to intestinal mucosa may potentially be used as one of antibiotic‐free strategies for the control of this disease. F4ac+ ETEC has been reported to bind to fat globule membrane in porcine milk. In this study, we used two different methods to identify individual milk fat globule membrane (MFGM) proteins that interact with F4ac fimbria. First, two‐dimensional SDS‐PAGE overlay Western Blot was used to demonstrate the interaction between F4ac and several MFGM proteins: namely, lactadherin, butyrophilin, adipophilin, acyl‐CoA synthetase 3, and fatty acid binding protein 3. Subsequently, affinity chromatography was designed to isolate the following F4ac‐binding proteins from the porcine MFGM: lactadherin, butyrophilin, adipophilin, acyl‐CoA synthetase 3, fatty acid binding protein 3, and xanthine dehydrogenase. Selected individual proteins and their subunits (e.g. carbohydrates) are being tested for their inhibitory effects against attachment of ETEC to porcine enterocytes. This project was supported by the Saskatchewan Agriculture Development Fund, WCVM Canadian Vitamins Class Action Settlement Fund.
Neuron‐targeted Cav‐1 as a novel therapy for Traumatic Brain Injury
Authors: Kellerhals Sarah Elizabeth , Niesman Ingrid , Kleschevnikov Alexander M. , Patel Hemal H. , Patel Piyush M. , Head Brian P.
Published: June 2021

Traumatic Brain Injury (TBI) is the leading cause of death in young adults in the civilian and military population in the Western world. TBI causes excessive release of glutamate, hyperactivation of NMDAR, excitotoxicity, and neuronal death. Membrane/lipid rafts (MLR) are plasmalemmal microdomains enriched in sphingolipids, cholesterol, and the protein caveolin (Cav) and are essential for pro‐growth neuronal signaling and synaptic development/stabilization. Cav‐1 organizes glutamate and neurotrophin receptors (e.g. NMDAR, AMPAR, GPCRs, Trk), pro‐survival kinases, and regulates cAMP formation. We have previously shown that neuron‐targeted Cav‐1 driven by a synapsin promoter (SynCav1) increased neuronal arborization in vitro. We have extended our studies to an in vivo mouse TBI model that utilizes a stereotaxic SynCav1 gene delivery before and after controlled cortical impact (CCI). Treatment with SynCav1 prior to CCI blunted TBI‐enhanced polysynaptic responses, a pre‐seizure indicator and augmented long‐term potentiation (LTP) of CA1 monosynpatic responses. Sucrose density fractionation, EM, and IF demonstrate SynCav1 delivery to the hippocampus protects CA1 neurons against CCI. Such data indicate that SynCav1 may be a novel therapy to limit brain injury following TBI.

Work supported by Veterans Affairs CDA‐2 (B.P. Head)
Proinflamatory cytokines affect dystrophin expression in cultured newborn cardiomyocytes under different stimuli
Authors: Malvestio Lygia Maria Mouri , Prado Cibele , Campos Érica , Celes Mara R.N. , Ferezin Patrícia , Silva João Santana , Rossi Marcos A
Published: June 2021

Previous studies from our laboratory demonstrated dystrophin disruption in the sepsis induced by cecal ligation and puncture in mice (CLP) and experimentally‐induced T.cruzi myocarditis. This study evaluated the dystrophin expression in cultured newborn cardiomyocytes stimulated with serum of mice infected with T.cruzi and serum of mice subjected to severe septic. Cardiomyocytes were incubated for 24 h with serum from chagasic mice or serum from septic mice, the controls cells received fetal bovine serum. The serums were obtained from C57Bl/6 mice infected with T.cruzi at the peak of parasitemia and the septic serum was collected from C57Bl/6 6 h after CLP. After incubation, the cells were processed to evaluate the expression of dystrophin, myosin and phalloidin. The immunofluorescent staining (IF) for myosin confirmed the presence of cardiomyocytes. The cells stimulated with serum from chagasic mice and septic mice presented disarrangement of myofibrils in the phalloidin staining compared to control. The IF for dystrophin showed vacuolization in the cytoplasm of cells incubated with serum from septic and T.cruzi infected mice. These results show that serum from chagasic and septic mice could be responsible for alterations in dystrophin expression in cardiomyocytes. It can be hypothesized that proinflamatory cytokines presented in serums of chagasic and septic mice could affect dystrophin expression.
Histological markers of Cardiovascular Diseases in a mouse model of social stress simulating aspects of PTSD
Authors: Urow Umid Farach , Melige Monique , Sowe Bintu , Chakraborty Nabarun , Carroll Erica , Meheroff James , Hammamieh Rasha , Jett Marti
Published: June 2021

Posttraumatic stress disorder (PTSD), a common psychiatric disorder, is associated with risk of cardiovascular (CV) atrophy and possible thromboembolic stroke. We examined the histology of cardiac samples from mice (C57BL/6) that had been subjected to social stress (SS) for 5 or 10 d. SS mice, housed with an aggressor mouse (AGG) for 6h/d sans food/liquid, were subjected to direct exposures with AGG at 3x/d at random times. Control mice (C) were put in the same environment without any direct agonistic interaction with AGG. Cardiac tissues were harvested 1d or 4wks after 10d SS, and 1d or 1.5wks after 5d SS, and were stained and examined under the brightfield optic. Cardiac tissues from C were harvested at the same time points.

SS‐induced cardiomyopathy, specifically degeneration and inflammation, was evident 24h after 10d and 5d among SS mice, but not C.

Animals showed almost no trace of CV pathology 4wks after 10d SD; although after 1.5wks post 5d SD, traces of CV atrophy persisted. While SS induced significant short term CV pathology, progressive remission was evident over 4 wks following cessation of SS exposure.
Signaling pathways involved in skeletal muscle response to oxidative stress in rats with heart failure
Authors: Martinez Paula Felippe , Guizoni Daniele , Junior Silvio Oliveira , Bonomo Camila , Damatto Ricardo , Lima Aline , Cezar Marcelo , Zornoff Leonardo , Okoshi Katashi , Campana Alvaro , Okoshi Marina
Published: June 2021

This study examined whether mitogen‐activated protein kinases (MAPK) and nuclear factor‐kappaB (NF‐κB) pathways participate in skeletal muscle response to oxidative stress in heart failure rats.

Methods

Myocardial infarction (MI) was induced by left coronary occlusion. Four months later, rats were assigned to three groups: Sham (n=8), MI without treatment (n=8), and MI/NAC (MI treated with the antioxidant N‐acetylcysteine, 120 mg/kg/day, n=8). Rats with small MI were excluded. Six months after surgery, total and phosphorylated forms of MAPK (JNK and p38) and NF‐κB proteins were analyzed by Westen blot in soleus muscle.

Results

MI size did not differ between MI and MI/NAC groups (P>0.05; Student's t test). Total JNK, p‐p38 and p‐NF‐κB did not differ among the groups. Table shows the other Western blot results.

Conclusion

Skeletal muscle response to oxidative stress is combined with JNK and NF‐κB protein expression changes in rats with heart failure. Support: FAPESP, CNPq, and Fundunesp.
Early rather than late aldosterone blockade improves myocardial function in spontaneously hypertensive rats without heart failure
Authors: CEZAR MARCELO DIARCADIA MARIANO , Junior Silvio , Martinez Paula , Damatto Ricardo , Lima Aline , Bonomo Camila , Guizoni Daniele , Campos Dijon , Moretto Fernanda , Blotta Daniella , Rosa Camila , Campana Alvaro , Okoshi Marina , Okoshi Katashi
Published: June 2021

The purpose of this study was to compare the effect of early and late aldosterone blockade with spironolactone (SPR) on ventricular remodeling in spontaneously hypertensive rats (SHR) without HF.

Methods

SHR were divided into four groups: control: CTL13 (n=20) 13 month‐old and CTL16 (n=72) 16 month‐old; SPR: SPR13 (n=24) 13 month‐old and SPR16 (n=34) 16 month‐old. SPR groups were treated with SPR for six months (20 mg/kg/day). Systolic blood pressure (BP) was measured. Echocardiogram (ECHO) was performed to evaluate cardiac structures and left ventricular (LV) function. Myocardial function was analyzed in LV papillary muscle preparations. Statistics: two way ANOVA and Student‐Newman‐Keuls. Significance: p<0.05.

Results

BP was not different between groups (CTL13: 184±24; SPR13: 197±22; CTL16: 199±43; SPR16: 200±35 mmHg; p>0.05). ECHO did not show differences between groups. In vitro evaluated myocardial function was improved in SPR13 vs. CTL13 group (developed tension (dT): 7.00±1.68 vs. 5.22±1.64 g/mm2; maximum rate of dT: 61.0±17.4 vs. 46.8±5.00 g/mm2/s; maximum rate of tension decline: 28.9±7.06 vs. 21.6±5.40 g/mm2/s; p<0.05). Mortality rate was significantly lower in SPR16 than CTL16 (38% vs. 71%; p<0.05).

Conclusion

Aldosterone blockade initiated at 13 months but not at 16 months induces beneficial effects on myocardial function and collagen accumulation in SHR without heart failure.
Ethanol extracts of fruiting bodies of Antrodia cinnamomea suppresses CL1‐5 human lung adenocarcinoma cells migration by inhibiting matrix metalloproteinase‐2/9 through ERK, JNK, p38 and PI3K/Akt signaling pathways
Authors: Chen Ying-Yi , Wu Chieh-Hsi , Sheu Ming-Jyh
Published: June 2021

Cancer metastasis is a primary cause of cancer death. Antrodia cinnamomea (A. cinnamomea), a medicinal mushroom in Taiwan, has been shown antioxidant and anticancer activities. In this study, we first observed that ethanol extract of fruiting bodies of A. cinnamomea (EEAC) exerted a concentration‐dependent inhibitory effect on migration and motility of the highly metastatic CL1‐5 cells in the absence of cytotoxicity. The results of a gelatin zymography assay showed that A. cinnamomea suppressed the activities of matrix metalloproteinase (MMP)‐2 and MMP‐9 in a concentration‐dependent manner. Western blot results demonstrated that treatment with A. cinnamomea decreased the expression of MMP‐9 and MMP‐2; while the expression of the endogenous inhibitors of these proteins, i.e., tissue inhibitors of MMP (TIMP‐1 and TIMP‐2) increased. Further investigation revealed that A. cinnamomea suppressed the phosphorylation of ERK1/2, p38, and JNK1/2. A. cinnamomea also suppressed the expressions of PI3K and phosphorylation of Akt. Furthermore, treatment of CL 1–5 cells with inhibitors specific for PI3K (LY 294002), ERK1/2 (PD98059), JNK (SP600125) and p38 MAPK (SB203580) decreased the expression of MMP‐2, and MMP‐9. This is the first report confirming the anti‐migration activity of this potentially beneficial mushroom against human lung adenocarcinoma CL1‐5 cancer cells.
Saussurea involucrata extract induces cell cycle arrest and apoptosis in HepG2 human hepatocarcinoma cells
Authors: byambaragchaa munkhzaya , Yoo Yng-Choon , Khajidsuren Altantsetseg , Hwang Seong Gu
Published: June 2021

Saussurea involucrata is a Mongolian pharmaceutical plant well known for its effect on promoting blood circulation, anti‐inflammation and analgesic functions. Very few earlier studies have reported that Saussurea involucrata has anti‐cancer activity. In order to evaluate the anticancer effect of Saussurea involucrata extract (SIE), HepG2 cells were treated with 50–400ppm of SIE. The underlying molecular mechanisms involved in antitumor activity of SIE were investigated by proliferation assay, FACS analysis, laser confocal assay, real time PCR and Western blotting. Treatment with SIE inhibited HepG2 cell proliferation dose‐dependently. The cells exposed to SIE showed typical hallmarks of apoptotic cell death such as chromatin condensation and DNA fragmentation. In addition, cell cycle analysis revealed that SIE caused G1‐phase arrest in HepG2 cells. But SIE exerted a modest cytotoxic effect on a viability of Chang human liver cells. SIE also suppressed mRNA expression of Bcl2 dose‐ and time‐dependently, but induced p21 and caspase‐3 protein expression. Both mRNA and protein expression of p21 were decreased at early time point and gradually increased preceding the onset of arrest at G1 phase. Collectively, SIE has antitumor activity to induce apoptosis of HepG2 cells, its apoptosis‐inducing activity may be related to activation of caspase‐3, increase of p21 expression, and cell cycle arrest to G1 phase.
Targeting the glycolytic pathway in cancer cells: glycolytic and regulatory functions of GAPDH
Authors: Krynetskiy Evgeny
Published: June 2021

Glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) is a pivotal enzyme of the glycolytic pathway, and a regulatory protein in several cellular networks. Knockdown of GAPDH induces senescence in human cancer cells A549, as revealed by senescence biomarkers SA‐â‐galactosidase and DEC1. To assess the potential role of GAPDH as a molecular target within the cancer energy metabolism network, we (1) characterized structural elements of GAPDH polypeptide pertinent to its intranuclear functions, and (2) evaluated sensitivity of GAPDH‐depleted cells against a panel of chemotherapeutic agents. We performed site‐mutagenesis of the functional domains in GAPDH, and estimated the enzymatic properties, intracellular distribution, and intranuclear mobility of GAPDH mutated variants. The fluorescence recovery after photobleaching experiments revealed that the substitution of Thr and Ser by non‐phosphorylated amino acid residues significantly increased intranuclear mobility of GAPDH. Our results indicate that GAPDH phosphorylation is important both for GAPDH enzymatic activity, and interactions with intranuclear components. Identification of intranuclear functional partners of GAPDH is expected to define targets for development of novel antiproliferative agents.
PENTOXIFYLLINE INITIATES GSK‐3β‐INDUCED PROTEASOMAL DEGRADATION OF CYCLIN D1 AND ARRESTS RENAL CANCER CELLS IN THE G1 PHASE
Authors: Mastrandrea Nicholas , Cai Wesley , Tham Kim , Monks Terrence , Lau Serrine
Published: June 2021

Cyclin D1 is required for cells to progress from the G1 phase into the S phase of the cell cycle. Several tumors display elevations in cyclin D1, concomitant with increased cell cycle progression and proliferation. QTRRE (rodent) and ACHN (human) cell models of renal cell carcinoma display elevated cyclin D1 protein levels. Pentoxifylline (PTX), a competitive non‐specific phosphodiesterase inhibitor, has found recent use as an adjunct in chemotherapy for patients to help treat cachexia and capillary leak syndrome. We report that PTX causes a time‐ (1–24 hr) and dose‐dependent (35 μM −3.5 mM) decrease in cyclin D1 protein levels in both cell lines. PTX's ability to decrease cyclin D1 in QTRRE and ACHN was abolished in the presence of a proteasome inhibitor (MG‐132, 10μM) as well as a GSK‐3β inhibitor (VI, 1μM). Consistent with decreases in cyclin D1, flow cytometric analysis revealed that QTRRE and ACHN cells treated for 24hr with PTX undergo enhanced cell cycle arrest in the G1 phase (170 & 140%, respectively). Collectively the data suggest that PTX decreases cyclin D1 protein levels by stimulating GSK‐3β‐induced proteasomal degradation, which promotes G1 phase cell cycle arrest. Moreover, because our findings reveal a novel anti‐cancer chemotherapeutic property of PTX, the utility of PTX as an adjuvant therapy in the treatment of cancer should be further explored. (AstraZeneca Studentship, T32ES016652, P30ES006694)
Disease stage‐specific G protein‐coupled receptor expression in clinical disorders: Chronic lymphocytic leukemia as a model
Authors: Katakia Trishna , Murray Fiona , Zhang Lingzhi , Gray Charles , Insel Paul
Published: June 2021

G protein‐coupled receptors (GPCRs) are attractive targets in disease since they are expressed on the plasma membrane and show tissue‐specific expression. A clinical problem for many heterogeneous diseases, such as Chronic lymphocytic leukemia (CLL), is the lack of markers that can predict prognosis. CLL, which is characterized by the accumulation of B‐cells, is classified as aggressive, which requires immediate treatment, or indolent, which does not require treatment. We hypothesized that patterns of GPCR expression are disease stage‐specific and used CLL as a model to test if such patterns can identify biomarkers and therapeutic targets. Using a TaqMan® GPCR array we found that normal B‐cells (n=10) express greater than 200 GPCRs (74 orphan receptors), indolent CLL cells (n=10) express greater than 170 GPCRs (74 orphan GPCRs) and aggressive CLL cells (n=10) express greater than 117 GPCRs (51 orphan GPCRs). Numerous GPCRs were uniquely expressed or altered in CLL and expression differed in the 2 stages of CLL. Expression of vasoactive intestinal polypeptide receptor 1 (VIPR1), a Gs‐coupled GPCR, increased >700‐fold in aggressive CLL compared to indolent, and VIP (1 μM, 48h) induced apoptosis of CLL cells (P<0.05, n=3). Thus, expression of particular GPCRs can provide stage‐specific markers and identify novel targets for the treatment of CLL or other heterogeneous diseases. Funded by NIH.