bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomimetic scaffolds and natural matrices for stem cell‐based tissue engineering and modeling (81.3)
Authors: Tuan Rocky
Published: June 2021

The intrinsically low reparative capacity of cartilage is a clinical challenge to effective treatment of degenerative joint diseases, such as osteoarthritis, the main cause of physical disability. Tissue engineering and regenerative medicine, combining cells, scaffolds, and biological signals, represents a potentially promising approach. Mesenchymal stem cells (MSCs), harvested from adult tissues such as bone marrow and adipose, have multi‐lineage differentiation potential, including chondrogenesis, and are considered a promising candidate cell type for cartilage repair. A biocompatible biomaterial scaffold that ideally also enhances proliferation and differentiation of the seeded cells is critical to successful cell‐based tissue engineering. We have shown that biomimetic scaffolds that simulate the structure of native extracellular matrix, e.g., the nanoscalar fibrous nature of collagen, are effective in MSC‐based skeletal tissue engineering both in vitro and in vivo. Our recent work on the use of custom‐designed, photo‐crosslinked hydrogel scaffolds, which allows cell encapsulation during fabrication, demonstrates high fidelity reproduction of internal structure and excellent cell retention, viability, and differentiation. Specifically, applying a 3D printing approach and a custom‐designed microbioreactor, we have constructed a microtissue analogue of the osteochondral junction, based entirely on MSC‐derived components, to model the pathogenesis of osteoarthritis. Adult stem cells, with their multi‐differentiation potential and recently discovered trophic activities, when used in combination with biomimetic scaffolds, present a powerful platform for regenerative, therapeutic, and disease modeling applications in biomedicine.
Glycemic load is positively associated with diastolic blood pressure levels during pregnancy: preliminary results from a prospective cohort study in Rio de Janeiro, Brazil (810.11)
Authors: Vilela Ana Amélia , Mendes Roberta , Franco‐Sena Ana Beatriz , Farias Dayana , Rebelo Fernanda , Rodriguez Camila , Kac Gilberto
Published: June 2021

Objective: To evaluate the association between dietary GL and systolic (SBP) and diastolic blood pressure (DBP) during healthy pregnancy. Methods: Prospective cohort of 155 healthy pregnant women followed at 6‐13th, 20‐26th and 30‐36th gestational weeks. Dietary GL was calculated from glycemic index, carbohydrate content, and frequency intake of selected foods, obtained from food frequency questionnaire applied in the 3rd trimester having the whole pregnancy as the time frame. SBP and DBP throughout pregnancy were the outcomes. Statistical analysis comprised multiple longitudinal linear mixed‐effect models adjusted for obstetric, socioeconomic, dietetic, and biomarker variables. Results: Mean SBP was 109.7, 107.9, and 111.3 (mmHg) and DBP was 66.6, 64.3, and 67.2 (mmHg) for the 1st, 2sd and 3rd trimester, respectively, and didn’t varied according to tertile of GL in the 3rd trimester (p>0.05). GL was not associated with SBP in the multiple model (β=0.237; 95%CI=‐0.16‐0.64; p=0.245). GL was positively associated with DBP (β=0.387; 95%CI=0.08‐0.69; p=0.015) after adjusting for confounders such as per‐capita family income, skin color, BMI, and calories. Conclusion: Dietary GL was positively associated with DBP changes during pregnancy.

Grant Funding Source: Supported by: FAPERJ, CNPq, CAPES
The snack preference could be used as a diagnostic indicator for hypertension in Korean teenagers (810.19)
Authors: Shin Dongsoon , Yun Suyoung
Published: June 2021

Nowadays metabolic syndrome is considered to be epidemic all around the world. The aim of this survey was to investigate the relationship of characters of metabolic syndrome and snack preference in teenagers around southern beach area of Korea. The subjects were 232 males and 232 females, total 464 high school students. Average of BMI range were 20.9~21.3, and blood glucose level after meal 2 hours was 98.8±13.0 mg/dL. There were no significant differences regardless of gender. However systolic pressure were boys 129.7±17.6 mmHg, girls 103.8± 9.7mmHg, respectively (p<.001), while their diastolic pressure were 70.0± 8.5mmHg similarly. At school time they had a snack for alternative meal or just habitually. Often boys also enjoyed snacks for feeling satiety between meals, but girls did for health or fitness (p<.01). Interestingly boys desired to eat whole‐grain breads, while girls did fresh fruits or vegetables as a healthy snack (p<.01). These results suggest that higher preference for whole‐grain breads rather than fresh fruit or vegetables would drive them to be hypertensive, which will deteriorate one of sings for metabolic syndrome.
Three statistical approaches to the estimation of intervention effect on a randomized cluster trial to reduce anemia and iron deficiency in children aged 12‐30 months (810.27)
Authors: Mendez Gomez Humaran Ignacio , Shamah Levy Teresa , Mendez Ramirez Ignacio
Published: June 2021

A double‐blinded, group‐randomized trial was conducted in 12 milk distribution clusters. After a randomization device, 7 clusters were assigned to consume iron‐fortified an 5 non‐fortified milk. The objective of the research, is to assess the effectiveness of a large‐scale program that distributes subsidized iron‐fortified milk in Mexico on anemia and iron deficiency in children aged 12‐30 mo. Randomized cluster trials, are experimental studies that attempt to balance confounding factors that affect outcomes across the study groups controlling for possible hidden bias, but randomization is never completely successful.The use of statistical methods to control variability in the study groups in order to make meaningful comparisons and describe characteristics of the groups being compared in order to find a reasonable amount of overlap is encouraged.

In this work we compare three statistical methods to establish effect estimates and control variability in the studygroups. First, it is common the use generalized linear models with several covariates to establish corrected effect estimates. Second, a simplest approach is the use cluster analysis to generate multivariate post stratums and use them in those models to control variability among groups. Finally, the use of propensity score matching procedures is useful to estimate treatment effects and approximated bias estimates. All three methods present different ways to address the roll of covariates in the understanding of the whole phenomena.
Food group sources and intake of long‐chain fatty acids in the Adventist Health Study‐2 cohort (810.30)
Authors: Heskey Celine , Jaceldo‐Siegl Karen , Sabate Joan , Rajaram Sujatha
Published: June 2021

Long chain fatty acids have unique and varying effects on health. Identifying common dietary sources of fatty acids can help in developing individual and public health recommendations regarding intake. The purpose of this descriptive study is to identify the food group sources of long‐chain fatty acids in the Adventist Health Study‐2 cohort. This cohort has approximately 96,000 participants (65% female; 26% Black; mean age 58.2 years) from the U.S. and Canada. A quantitative 204 food‐item food frequency questionnaire (FFQ) was used to measure food intake. The FFQ was used to estimate fatty acid intake, identify 14 major and 51 minor food groups, and define dietary patterns (vegan (7.6%), vegetarian (28.9%), semi‐vegetarian (5.5%), pesco‐vegetarian (9.8%), and non‐vegetarians (48.2%)). Preliminary results show mean dietary intake (per 2000 kcal) of 72.1 g total fat, 17.7 g linoleic acid, 0.02 g arachidonic acid, 1.85 g α‐linolenic acid (ALA), 16 mg of eicosapentaenoic acid and 39 mg docosahexaenoic acid. Estimated ALA (0.8% kcal) and linolenic acid (8% kcal) intake meets the dietary reference intake of 0.6‐1.2 and 5‐10% kcals, respectively. Average dietary EPA+DHA intake in this cohort is less than the American Heart Association recommendation of 0.5‐1 g for prevention of heart disease. Further analyses will determine food sources of these fatty acids within each dietary pattern.
Qualitative validation and construction instrument for measuring well‐being perception associated with water consumption (810.32)
Authors: Espinosa Juan , Monterrubio Eric , Castañeda Sandra , Barquera Simon
Published: June 2021

An instrument for assessing well‐being perception associated with water consumption (IPBA) in adults for low socioeconomic status in Cuernavaca, Mexico was constructed and validated. Focus groups were made as well as semi‐structured interviews including adult men and women (21‐59 years old) who are sedentary. Two groups of people with a different consume of water were formed: the ones who consume a lot of water (> 2.0L total liquids (TL) and plain water (PW) < 1L) and the ones who hardly consume any water (< 1.5L of TL and PW < 0.3L). Guidance was used to investigate the meaning of well‐being by PW consumption from the knowledge, attitudes, beliefs and perceptions of everyday life. Internal consistency was assessed by means of Cronbach´s Alpha (CA). Sessions were leaded by expert psychologists and were audio recorded under the oral consent of participants.

Items were created from keywords and symptoms related to hydration. IPBA was adjusted by pilot testing; was revised by experts on hydration and sent to judges for validating facie and construct. A total of 55 items were chosen; such items reference perception of well‐being in the last 7 days and uses a liker‐type answer scale (Always, almost always, sometimes, almost never, never). The IPBA identifies two dimensions (Physical well‐being and mental well‐being) with a CA of 0.83 and 0.91 respectively. In a subsequent phase exploratory and confirmatory factors analyses are performed.

IPBA is the first proposal of instrument for measuring well‐being perception related to hydration. The construction of items was based on empirical evidence about how the target population senses well‐being related to hydration.

Grant Funding Source: Sponsored/funded by Instituto Danone de Mexico
Modification in milk fatty acids during processing to whey protein concentrate (813.11)
Authors: Silva Luciana , Quintanilla Andrew , Espinosa Kristen , Macha Aaron , Wells Shawn , Wildman Robert
Published: June 2021

Whey Protein Concentrate (WPC) is used as an ingredient in many foods and is a desirable protein source in sports nutrition products. By and large WPC is produced from the whey fraction byproduct of cheese production called “sweet whey” and undergoes microfiltration to remove fat (whey cream) and ultrafiltration to remove much of the carbohydrate (primarily lactose) content. On a dry weight basis WPC approximates 80% protein, 5‐6% carbohydrate (mostly lactose) and 6‐8% lipids. While most of the attention is focused on the whey protein content, little attention is afforded to the unique and potential beneficial lipid fraction of WPC such as butyric acid and long chain fatty acids including omega‐3 and omega‐6 fatty acids. Moreover, little attention is provided to the effects of processing sweet whey to WPC on the resulting proportion of fatty acids in the reduced fat WPC. In this study, samples of sweet whey, whey cream and WPC from the same production lot were analyzed for fatty acid composition. The total fatty acid content of whey cream is 30.4% while WPC was 4.3%. Comparatively the proportion of butyric acid and other SCFA and MCFA were lower and longer chain PUFAs where higher in the WPC versus the whey cream. For instance, SCFAs butyric acid (4:0) and caproic acid (6:0) were 30.3% and 41.8% and MCFAs caprylic acid (8:0) and capric acid (10:0) were 65.6% and 65.4% concentration levels versus whey cream. Meanwhile, content of linoleic acid (18:2 n‐6) was assessed to be doubled versus whey cream (5.84% vs 2.84%). These findings are aligned with the notion that more of the relatively smaller lipid molecules would be removed during microfiltration while larger, more complex fatty acids would remain with the protein.
Identification and functional characterization of an alternative 5’ exon of the sodium dependent ascorbic acid transporter SLC23A1 (818.5)
Authors: Amir Shaghaghi Mandana , Yurkova Natalia , Tu Hongbin , Levine Mark , Eck Peter
Published: June 2021

Vitamin C, an essential micronutrient and a critical cofactor for several intracellular enzymatic reactions, is actively transported across epithelial barriers through the sodium‐dependent ascorbic acid transporter 1 (SLC23A1). The SLC23A1 gene encodes SLC23A1 transporter and is located on human chromosome 5q31.2 (138702885‐138719039 compl.; NC_000005.9). Previously, the SLC23A1 transcript has been described as containing 15 exons, stretching over 16 kilobases; however, no alternative splice variant has been described yet. Variations in SLC23A1 gene would impact vitamin C dietary requirements and/or susceptibility to common complex diseases. We have, therefore, evaluated the existence of additional SLC23A1 transcripts in silico and examined the function of new transcript through Xenopus laevis oocytes injection. Here, we characterized a novel alternative first exon encoding a SLC23A1 isoform which is exclusive to human and is expressed in the small intestine. The novel SLC23A1 protein isoform adds 36 N‐terminal amino acids but does not alter transmembrane topology or intracellular location. The novel SLC23A1 isoform is located on the plasma membrane and mediates very low ascorbic acid transport when expressed in Xenopus laevis oocytes. This is the first report of an alternative splice variant in human SLC23A1 locus and confirmed an extension of about 1kb further 5’ than previously described gene.

Grant Funding Source: This work was funded through Peter Eck’s Canada Research Chair in Nutrigenomics award and in part b
Leucine activation of mTORC1 in skeletal muscle cells is inhibited by the lysosomotropic agent chloroquine (820.2)
Authors: Borack Michael , Rasmussen Blake
Published: June 2021

Recent work in human embryonic kidney cells has uncovered many of the cellular mechanisms underlying amino acid activation of the mTORC1 signaling pathway. It is now known that mTORC1 translocation to the lysosomal surface is required for the amino acid activation of mTORC1 signaling. It is not known if the lysosome is required for amino acid activation of mTORC1 in skeletal muscle cells. To test this hypothesis, we exposed C2C12 muscle cells (that were plated and differentiated into myotubes for 7‐8 days) to both leucine and a potent lysosomal inhibitor (chloroquine). Cells were placed into three groups: control (1), leucine only (2) and leucine+chloroquine (3). The first two groups were taken out of media and starved in a Hepes buffer for 9hrs. Group 3 was starved for 8hrs followed by a 1hr starve in 2000ug/ml chloroquine in the same Hepes buffer. Groups 2 and 3 were given 1mM leucine for ten minutes before collection. Western blotting was used to determine phosphorylation of mTOR and its downstream targets. The leucine only group showed a significant increase in mTOR and p70s6k phosphorylation compared to control and leucine+chloroquine groups (p<0.05). It appears that disruption of lysosomal function by chloroquine blocks leucine activation of the mTORC1 signaling pathway in skeletal muscle cells. Future work will determine the role of the lysosome for amino acid activation of mTORC1 in vivo.

Grant Funding Source: Supported by NIH AR049877
Effect of nuts on coronary heart disease and cancer risk in type 2 diabetes (825.8)
Authors: Nishi Stephanie , Kendall Cyril , Bashyam Balachandran , Augustin Livia , Jenkins David
Published: June 2021

Background: Diabetes increases the risk of coronary heart disease (CHD) by 2‐4 fold, and the risk of the majority of cancers by 1.2‐2‐fold, where CHD and cancer are two of the leading causes of morbidity and mortality worldwide. Dietary factors have long been implicated in both cancer and CHD, where diet and lifestyle changes are said to reduce risk by 10‐80%. Nuts are one dietary factor that have been associated with reduced CHD and cancer risk in epidemiological studies.

Objective: To determine the effect of nut consumption on cancer cell proliferation and its association with oxidative damage.

Methods: A 12 week randomized controlled trial was completed by 100 participants with type 2 diabetes consuming one of 3 isocaloric supplemental diets; 1) full‐dose nut diet (~75 g mixed nuts per day), 2) half‐dose nut diet, or 3) control diet, incorporated into a background NCEP Step 2 diet. In vitro prostate cancer cell (LNCaP) proliferation, used as a marker of cancer risk, and markers of oxidative damage for CHD risk were analyzed using available fasting blood obtained at weeks 0 and 12.

Results: No treatment differences were observed. However, across treatments, when data were pooled, nut consumption was associated with increased protein thiols (P=0.001) and decreased LNCaP proliferation (P=0.01). Conjugated dienes were positively correlated with LNCaP proliferation (R=0.22, P=0.03).

Conclusion: Nut consumption has been associated with reduced CHD risk, though more studies may be required to elucidate the mechanism for CHD reduction, as well as the effect on cancer risk.

Grant Funding Source: Supported by the Canadian Foundation for Dietetic Research (CFDR)
Choline deficiency decreases proliferation of embryonic neural progenitor cells through inhibiting epidermal growth factor pathway (827.2)
Authors: Wang Yanyan , Mehedint Mihai , Corbin Karen , Friday Walter , Zeisel Steven
Published: June 2021

Choline deficiency can alter the development of fetal hippocampus. Epidermal growth factor (EGF) is pivotal for neural progenitor cell (NPC) proliferation in the embryonic ventricular and subventricular zones. To address the possibility that EGF signaling pathway plays a functional role in the effect of choline deficiency, we cultured NPCs derived from E14 mouse hippocampus and treated them with low choline (5 µM) or medium choline (70 µM). Low choline significantly suppressed the phosphorylation of EGF receptor (EGFR) and activation of downstream effectors ERK1/2 and Akt after stimulation of NPCs with EGF. Moreover, low choline decreased the EGFR protein expression and half‐life in NPCs. There were no changes observed on the EGFR mRNA expression and degradation of EGFR protein. However, low choline remarkably inhibited the EGFR nascent protein synthesis. Our findings reveal that choline deficiency influences NPC proliferation by suppressing EGFR signaling pathway, which might have long‐term effects in the brain.

Grant Funding Source: North Carolina Biotechnology Center (NCBC)
Nutritional content of common Amaranthus hybridus vegetable (Efo Tete) in Nigeria (828.4)
Authors: Oyelola Olukemi , Banjoko Immaculata , Ajioshin Isaac
Published: June 2021

Generality of Nigerians depend on starch‐based foods as the main staple food for the supply of both energy and protein. This accounts in part for protein and mineral deficiency which prevails among the populace. Many of the local vegetable materials are under‐exploited because of inadequate scientific knowledge of their nutritional potentials. The focus of this study was to determine the nutritional value of Amaranthus hybridus vegetable commonly consumed by the generality of the people. The vegetable seeds were planted in five different locations in the Botanical Garden of Yaba College of Technology and harvested after eight weeks. The freshly harvested leaves from each of the locations were subjected to proximate and micronutrient analyses using standard analytical methods. The Proximate analysis showed the percentage moisture content 84.0%, ash 12.70%, fat 3.25%, protein 16.38%, crude fibre 7.9% and carbohydrate 50.77%, while its calorific value was 289.92 Kcal/100g. The dietary mineral content values in mg/100g are calcium 153+1.3 phosphorus 63.20+ 1.04, potassium 370.12+ 2.84, magnesium 215+ 1.06, iron 12.5+ 0.47, sodium 3.72+ 0.15, copper 0.67+ 0.05, zinc 1.32+ 0.10, cobalt 0.52+ 0.08, selenium 0.067+ 0.03, and chromium 1.36+ 0.13. These results showed that the vegetable contained an appreciable amount of nutrients and mineral elements that could be included in diets to supplement the daily requirement by the body. Consumption of the vegetable will help average Nigerians to obtain the minerals required for healthy living.
Chardonnay grape seed flour alters expression of hepatic genes for lipid and glucose metabolism, inflammation, and leptin receptor (829.13)
Authors: Kim Hyunsook , Bartley Glenn , Chon Jung‐Whan , Seo Kun‐ho , Yokoyama Wallace
Published: June 2021

To determine whether flavonoid‐rich wine grape seed flour improves insulin sensitivity and glucose metabolism in obese mice, diet‐induced obese (DIO) mice were fed a HF diet supplemented with either 10% partially defatted Chardonnay grape seed flours (ChrSd) or microcrystalline cellulose (MCC, control) for 4 weeks. The 2‐h insulin and glucose areas under the curve were lowered by ChrSd indicating that ChrSd enhanced insulin sensitivity and improved glucose metabolism. ChrSd intake also reduced body weight gain, liver and adipose tissue weight, and plasma total and LDL‐cholesterol concentration despite a significant increase in food intake. Exon microarray analysis of hepatic gene expression revealed down‐regulation of genes related to gluconeogenesis, inflammation, triglyceride synthesis, and polyunsaturated fatty acid elongation, and up‐regulation of genes related to fatty acid oxidation, cholesterol and bile acid synthesis. The expression of hepatic leptin receptor was up‐regulated by the ChrSd diet supporting a role for leptin in the reduction of insulin resistance, inflammation, and hepatic steatosis. Analysis of the microarray data identified TCA cycle II, gluconeogensis, and glycolysis pathways as being differentially regulated by the ChrSd diet. In conclusion, Chardonnay grape seed flour ameliorates the effects of a HF diet on insulin resistance, hepatic lipid accumulation and glucose production, inflammation, and weight gain in DIO mice.
Anti‐diabetic effect of mixed raw food containing germinated barley and wheat with less side‐effect in SD rats and db/db mice model (829.15)
Authors: Zhou Bing , Lee Sang‐Hyun , Kim Jin‐Kyoung , Kwon Young‐In , Jang Hae‐Dong
Published: June 2021

The blood glucose lowering effect and side‐effect reducing potential of the mixed raw food (Saengshik) which contains germinated barley extract (GBE) and germinated wheat extract (GWE) were investigated in SD rats and db/db mice model. Saengshik was prepared by mixing different kinds of raw food with GBE and GWE. According to the results of blood glucose, HbA1c, insulin, HOMA‐IR analysis, Saengshik with GBE and GWE can not only lower the blood glucose level, but also improve insulin resistance both in SD rats and db/db mice. Saengshik with GBE and GWE significantly reduced total glyceride (TG) and total cholesterol (TC) in db/db mouse compared to the control group. In addition, the several symptoms of side effects including enlarged cecum, reduced intestinal transport activity and increased starch contents in feces were notably improved by Saengshik feeding compared to the Acarbose group in SD rats and db/db mice. Our results indicate that Saengshik with GBE and GWE may have a potential to be served as useful dietary strategy for diabetes.
In vivo therapeutic modulation of stress response signaling by Pitanga (Eugenia uniflora) extracts in C. elegans for neuroprotection (829.24)
Authors: de Medeiros Katia , Stavinoha Rebecca , Correia Roberta , Vattem Dhiraj
Published: June 2021

The effect of red (RP) and purple (PP) Pitanga (Eugenia uniflora) L. spray dried and freeze dried powders on modulating stress response signaling was evaluated in transgenic C. elegans carrying promoter‐GFP constructs for several genes in the IGFR/PI3K/AKT, ARE/NRF2, Sir2.1/AMPK, mTOR/HIF‐1α, apoptosis/cell cycle and UPR signaling pathways. Relative fold changes in gene expression in response to pitanga treatments were quantified flurometrically. Neuroprotective effects of RP and PP in experimentally induced neurodegeneration were evealuated in C. elegans models for Alzheimer’s disease (AD) and Parkinson’s disease (PD). For AD, time to thermally induced Aβ1‐42 aggregation mediated paralysis was evaluated in transgenic C. elegans (CL4176). For PD, MPP+ induced neurodegeneration was qualtified by loss in motility due to paralysis. Results suggest an upregulation in ARE and Sir2.1 signaling in response to Pitanga treatment. Treatment with polar acidic, polar basic and polar neutral fractions, abrogated Aβ1‐42 induced paralysis and MPP+ induced neurodegeneration for PD by 15‐22%. The processing technology used to produce Pitanga powders significantly impacted bioactivity.

Grant Funding Source: Supported by: Vrdür Foundation (USA) & CAPES (Brazil)
Dietary intake of antioxidant nutrients and peripheral plasma determination of T‐BARS in normal weight and obese Mexican people (830.14)
Authors: Hernandez‐Guerrero Cesar , Garcia‐Del Rio Sandra , Romo‐Palafox Ines , Hernandez‐Chavez Paulina , Zelonka‐Montes de Oca Rosa , Perez‐Lizaur Ana
Published: June 2021

The study objective was to evaluate the consumption of antioxidants and the oxidative stress condition in the peripheral compartment of Mexican obese people. The control group (CG) included 52 participants with a BMI of 18.5‐24.9. The overweight (OW) group included 31 participants with BMI of 25‐29.9 and the obesity group (OB) included 64 participants with IMC>30. A standardized antioxidant food frequency survey was applied to assess the intake of antioxidant vitamins A, C, E and the minerals: Cu, Mn, Se and Zn. T‐BARS concentration was assayed in plasma spectrophotometrically. The intake of vitamins, minerals and the T‐BARS concentration were compared with ANOVA of Kruskal‐Wallis between groups; a p<0.05 was accepted as a statistical difference. There were not differences between the consumption of minerals and vitamins between the CG, OW and OB groups. The concentration of T‐BARS in CG, OW and OB were 5.5+/‐3.8 µM, 6.1+/‐5.2 µM and 15.9+/‐8.2 (p<0.05 versus CG), respectively. When OB group was stratified by obesity degrees the concentration of T‐BARS were 14.9+/‐8.9, 15.2+/‐6.7 and 14.8+/‐8.1 for OB‐1 (BMI 30‐34.9), OB‐2 (BMI 35‐39.9) and OB‐3 (BMI>40), respectively. There were no statically differences between stratified OB groups and all of them showed difference (p<0.05) versus CG. The consumption of vitamins and minerals by CG, OW and OB groups showed similar values; however the oxidative stress marker (T‐BARS) in peripheral plasma of OB group showed a robust increase in comparison with CG and OW groups, respectively.

Grant Funding Source: Supported by Universidad Iberoamericana Ciudad de Mexico
Konjac glucomannan and inulin modulated the immune function in a murine model of dextran sodium sulfate‐induced colitis (830.2)
Authors: Han Yi‐Chun , Chen Hsiao‐Ling Chen
Published: June 2021

This study was to investigate the protective effects of konjac glucomannan (KGM) and inulin on colonic colitis in a dextran sodium sulfate (DSS)‐induced murine model.

During the 21‐d diet period, six‐week‐old C57BL/6J mice were randomly assigned and fed AIN‐93 diet (vehicle, DSS group) or fiber‐supplemented (KGM 2%, Inulin 2%, or KGM 1% + Inulin 1% w/w) diet. In the following 5‐d DSS period, all mice were fed AIN‐93 fiber‐free diet while drinking water with DSS (3% w/v) was offered only to DSS and fiber groups. Mice were sacrificed on the 3rd of DSS‐withdrawn period. The colonic tissues were collected to determine the pathohistology and gene expression of tight junction proteins by RT‐PCR. The plasma TNF‐α and IL‐10 were also analyzed.

DSS group had the greatest weight loss and DAI throughout the DSS period and its index of colitis continued to increase in the DSS‐withdrawn period. At the end of the study, the crypt depth was reduced at the proximal colon and severe colitis occurred at the distal colon in the DSS group, which was ameliorated with fiber supplementation. In addition to that, soluble fiber normalized the DSS‐induced alteration in the plasma TNF‐α and IL‐10 levels and the gene expression of occludin.

Pre‐supplementation of KGM and inulin prevented the colitis‐related symptoms in the DSS‐induced colitis.
Purple Perilla frutescens extracts enhanced cholesterol efflux and inhibited ER stress in macrophages exposed to oxidized LDL (831.8)
Authors: Park Sin‐Hye , Kang Young‐Hee
Published: June 2021

There is growing evidence that excess lipids can stimulate endoplasmic reticulum (ER) stress in atherosclerosis. However, the pathophysiological importance and the underlying mechanisms of this phenomenon remain unknown. The current study tested that oxidized LDL promoted ER stress in macrophages, which was blocked by purple Perilla frutescens extracts (PPE). The ER stressor tunicamycin was employed as a positive control. Treating oxidized LDL for 24 h accumulated lipid droplets in macrophages and formed foam cells, evidenced by Oil red O staining. PPE suppressed foam cell formation, but enhanced ATP‐binding cassette (ABC) transporter A1 and G1, cholesterol efflux markers. Oxidized LDL as well as tunicamycin induced the ER stress markers of activating transcription factor 6 and this effect was blocked by 蠅5 μg/ml PPE, indicating that intracellular toxic lipids in macrophages initiated ER stress. PPE also down‐regulated the induction of the ER resident chaperone BiP/Grp78. The LXR ligand TO‐0131917 increased ABCA1 expression that was blunted by the ER stressor. Accordingly, an upstream mechanism that links toxic lipids to ER stress may entail the action of lipid chaperones through inhibition of LXR. Purple Perilla frutescens extract (PPE) is an annual herb of mint family, which has possessed against inflammation and cancer. Therefore, PPE enhanced cholesterol efflux and inhibited ER stress in macrophages exposed to lipotoxic signals associated with atherosclerosis.

Grant Funding Source: Supported by Ministry for Food, Agriculture, Forestry and Fisheries and Brain Korea 21 plus
Transmigration of M1 and M 2 macrophages in pulmonary vessels following intratracheal bleomycin (834.7)
Authors: Wang Ping , Martin William
Published: June 2021

We have demonstrated macrophage transmigration in pulmonary vessels in murine lungs following bleomycin (Am J Pathol. 2011 Jun; 178(6):2560‐72). Because there are two distinct phenotypes in macrophages, M1 and M2, we wanted to compare the difference between them in transmigration of pulmonary vessels. To address this, we intratracheally instilled bleomycin (3.33 U/kg) into female adult mice (C57BL/6J, n=8). Lungs were isolated at day 2‐21 after bleomycin and cryostat sectioned for immunostaining with iNOS and arginase I to identify M1 and M2 macrophages, respectively. We used ki67 as the marker of cell proliferation. We used confocal microscopy to image pulmonary vascular region covered from the lumen to the perivascular interstitium. We found that more macrophages expressed arginase I [6.7‐fold to iNOS, p<0.05, unpaired t‐test], indicating that more M2 than M1 macrophages transmigrated in pulmonary vessels after bleomycin. Also, up to 20% M2 macrophages revealed ki67 expression (2‐fold to M1 macrophages, p<0.05) in arteriolar region, indicating higher local proliferation of M2 macrophages there. Our results provide direct evidence that primarily M2 macrophages transmigrated in pulmonary vessels. In addition, M2 exhibited more proliferation than M1 macrophages in pulmonary arterioles after bleomycin. This suggests an important role of M2 macrophages in bleomycin‐induced inflammation. (Funder: NIH)

Grant Funding Source: NIH
The bronchial hyperactivity in children with pollinosis (834.9)
Authors: Saparova L. , Rozenson R.I. , Abduldayeva A.
Published: June 2021

Aim of the study was to develop an easy available technique of lung function monitoring in pollinosis patients to predict the clinical course of disease both in seasonal exacerbation period and during the winter remission. Material: We studied 98 children with pollinosis aged 6‐14 years. Peak flow (PF) parameters were studied 3 times per day, namely in the morning, lunch time and in the evening, from the first of April to 30th October. Patients’ history records included hay fever symptoms and peak flow data. The curves of PF were drawn for disease monitoring and prediction. Results: Analyzing the daily changes of peak expiratory flow parameters, we estimated that in children with hay fever sensibilization to Artemisia species without evident asthma symptoms already at the second season peak expiratory flow decreased by 15‐20% and during the third season decreased further by 30% from the best parameters of the first year.

Most striking in our studies was the finding that after the pollination season especially in children with disease duration more than 3 years and who did not receive the specific immunotherapy the level of changes decreased, but the type of PF curve didn’t change. In prognosis the most important was the possibility of pollen asthma appeared in most children already during the second hay fever season and was easy predictable by “bad” peak expiratory flow curves ‐ second and third type.
Standardization method using argon plasma electric on strains of yeast genus Candida (836.7)
Authors: Sorge Camila , Rodrigues Fabiana , Doria Anelise Cristina , Santos Thaisa , Teodoro Guilherme , Oliveira Elizabeth , Lázaro João , Khouri Sônia
Published: June 2021

Fungal sepsis is the leading cause of death among hospitalized patients, 80 % caused by Candida species. The electric plasma has been widely used in the sterilization of materials, and easy handling, fast and safer than current methods of microbial control. The study is focused on the standardization of a technique physicochemical control based on the use of the electric plasma argon ‐ oxygen. Strains of Candida albicans ATCC and clinics, were grown in Sabouraud agar for 24 h at 37 °C and subsequently diluted in sterile saline to 0.9 %, according to the scale 0.5 MacFarland then promptly plated in Sabouraud. The plates were irradiated with plasma DBD (Dieletric Barrier Discharge 04W) at time zero, six and ten minutes and observed after 24 and 48 hours of incubation at 37 ° C. Through this methodology, it was observed that after irradiation of ATCC strains at times of 6 and 10 minutes, there was a reduction in the growth ofCFU 's of 50 and 100%, respectively reducing and of 86 and 95.7 % in clinical strains . The results are shown promise for the use of new techniques for sterilization of hospital supplies and possible application to control fungal biofilms using plasma jet.
The role of the locus coeruleus in the coping response to social stress (839.1)
Authors: Melson Michael , Wood Christopher , Lombard Calliandra , Wood Susan
Published: June 2021

Psychosocial stress is linked to psychiatric disorders such as depression. Using a social stressor in rats (resident‐intruder model) we previously identified two phenotypic responses to social stress. One population (45%) exhibited a passive coping response and assumed a defeat posture within a short latency (SL, <300s). The other phenotype (55%) exhibited proactive coping behaviors and a longer defeat latency (LL, >300s). Furthermore, SL rats developed endocrine and behavioral characteristics resembling depression, while the LL phenotype remains resilient. As the locus coeruleus (LC) is a stress‐sensitive brain region that is implicated in the stress coping response, it may mediate individual differences in the response to social stress and resulting pathology. Therefore the present study utilized the neurotoxin DSP‐4 to selectively lesion the noradrenergic LC prior to social stress. DSP‐4 treated rats exhibited decreased active coping behaviors upon the first exposure to social stress (upright posture: veh; 124±40, DSP‐4; 56±42). Furthermore, 5 days after the 5th exposure to social stress, DSP‐4 rats exhibited a reduction in sucrose intake compare with controls (Con: 84%, Veh: 80%, DSP‐4, 72%). These data suggest that lesioning the LC shifted rats towards a passive coping response and increase anhedonic behaviors. Therefore, the LC may mediate a protective effect over consequences of social stress.

Grant Funding Source: Supported by NARSAD 17830 and 13BGIA 14370026
Social learning reverses conditioned aversion to nicotine via oxytocin receptor in the infralimbic cortex in rats (839.4)
Authors: Han Wenyan , Chen Hao
Published: June 2021

The initial aversive response to cigarettes in most smokers is thought to be ameliorated by the presence of peers who also smoke. We previously reported that social learning (i.e. detecting an odor cue associated with nicotine from peer rats) reversed the development of conditioned taste aversion (CTA) between self‐administered nicotine and a contingent olfactogustatory cue in adolescent rats (PMID:21796102). Herein, we focused on the role of oxytocin in infralimbic cortex (IL) as a mechanism for the effect of social learning. Bilateral lesions of IL before (F1,13=18.1, p=0.001) but not after (F1,16=0.481, p>0.05) self‐administration reduced the effect of social learning on tests of CTA. We also found that carbon disulfide contained in rats’ breath was the signal mediating social learning and its effect also required intact IL. We then infused a specific oxytocin receptor antagonist, desGly‐NH2‐d(CH2)5[D‐Tyr]OVT, (0.028 ~ 2.8 μg/ml, a gift from Dr. Mannings) bilaterally into the IL, which dose‐dependently reduced the effect of carbon disulfide on nicotine CTA (F4,30=3.9, p=0.01). The highest dose of the antagonist had no effect on i.v. saline control rats. These results suggested that the release of oxytocin in the IL is a critical signal that reversed the conditioned aversion between nicotine and its olfactogustatory cue, which in turn enabled voluntary nicotine intake in adolescent rats.

Key words: nicotine; aversion; social learning; infralimbic cortex; oxytocin
The role of adenosine in helper T cell differentiation and function (840.1)
Authors: Klann Jane , Drygiannakis Ioannis , Gomez Bobbie , Thai Rosarlin , Ernst Peter
Published: June 2021

Background and Aims: Extracellular signaling molecules, such as anti‐inflammatory adenosine, play a major role in restraining immune response and protecting tissue from inflammatory damage. Adenosine is generated from the ATP through the action of ectonucleoside triphosphate diphosphohydrolase 1 (CD39) that sequentially dephosphorylates ATP to ADP to 5’‐AMP, which is then catabolized to adenosine by ecto‐5'‐nucleotidase (CD73, Nt5e). The aim of this study was to investigate the role of extracellular adenosine in control of helper T cell (Th) cell differentiation and cellular function. Results: Adenosine levels were controlled with a pharmacological approach using the non‐hydrolysable adenosine analog, NECA. Naïve CD4+ T cells were differentiated in vitro in the presence or absence of NECA in selective culture conditions. The presence of NECA suppressed the production of IL‐17a in cells isolated from Th17 conditions. We then explored a genetic approach to control adenosine levels in vivo, using an adoptive transfer colitis model. According to the model, the transfer of CD4+CD45RBhi cells, a subset that contains largely T effector (Teff) cells, will induce colitis when transferred to Rag1‐/‐ mice. Colitis can be ameliorated with the co‐transfer of CD4+CD45RBlo, a cell population with a primarily regulatory phenotype. T cells were isolated from Nt5e‐/‐ mice to investigate the function of Th cells compromised in the ability to produce adenosine. In our adoptive transfer studies, CD73 on both Treg and T effector proved to be necessary for Treg to prevent Teff‐induced colitis. Conclusions: Adenosine signaling has the ability to restrain Th17 response during differentiation through the direct reduction of the production of the pro‐inflammatory cytokine IL‐17a. The ability to produce adenosine is essential for effective Treg activity and compromising the adenosine pool changes the differentiation patterns of Th cells causing excessive inflammatory activation and tissue damage.

Grant Funding Source: Supported By: T32 Gastrointestinal Training Grant
Effects of oroxylin A in cerebral vascular tone regulation (841.3)
Authors: Tsai Andy , Chen Mei‐Fang , Liew Hock‐Kean , Chen Yen‐Chou , Tseng Tzu‐Ling , Pang Cheng‐Yoong , Lai Chih‐Chia , Lee Tony
Published: June 2021

Oroxylin A, a flavonoid and an active component isolated from Scutellariae baicalensis, has been considered beneficial in preventing inflammation‐induced microglia‐mediated neurodegeneration. Its role in regulation of cerebral vascular smooth muscle tone and blood flow, however, remains unclear. This study was designed to assess possible beneficial effects of oroxylin A in cerebral blood flow and cerebral vascular smooth muscle tone regulation in vitro and in vivo. The results indicated that oroxylin A (10 mg/Kg, iv), which did not affect the systemic blood pressure, significantly increased regional cerebral blood flow in the striatum of the rat in vivo, using laser Doppler flowmetry. Results from tissue bath myography studies indicated that oroxylin A (100 nM ‐ 30 μM) in a concentration‐dependent manner relaxed U46619‐precontracted porcine isolated basilar arteries. The vasorelaxation was not affected by denudation of the endothelium, cold storage for 5 days, tetrodotoxin (0.3 μM), ODQ (10 μM, a soluble guanylate cyclase inhibitor), SQ22536 (200 μM, an adenylate cyclase inhibitor) and H89 (10 μM, an inhibitor of protein kinase A), but was blocked by iberiotoxin (100 nM). These results suggest that oroxylin A induces dilation of large pial arteries and intraparenchymal vessels. The relaxation in large basilar arteries is independent of the endothelium and is mediated by large‐conductance Ca2+‐activated K+ channels on the smooth muscle cells. The vasodilatory effect with increased regional cerebral blood flow of oroxylin A may provide additional benefits in preventing inflammation‐mediated neurodegeneration.
Captopril treatment improves endothelium dependent dilation and middle cerebral artery remodeling in hypertensive rats (841.8)
Authors: Matin Nusrat
Published: June 2021

Hypertension is associated with cognitive deficits. Angiotensin converting enzyme inhibitors (ACEI) improve cognitive decline in hypertensive patients. We hypothesized that centrally active ACEI captopril (CTP) would alleviate cognitive function by improving endothelium dependent dilation and middle cerebral artery (MCA) remodeling from stroke prone spontaneously hypertensive rats (SHRSP). Data are shown as mean±SEM, SHRSP vs CTP and are analyzed by Student’s t‐test. 12 week old male SHRSP received CTP (50 mg/kg/day) for 6 weeks. Cognitive function, evaluated by Morris water maze, showed no difference between groups. CTP reduced systolic blood pressure (178±8 vs 131±6 mmHg, p<0.05). MCA reactivity and passive structure was assessed by pressure myography (data shown at 80 mmHg). CTP did not increase lumen diameter (232.6±8.1 vs 249.1±8.1). CTP reduced wall thickness (21.9±0.1 vs 17.3±1.0 µm, p<0.05) and wall/lumen ratio (0.1±0.01 vs 0.07±0.01, p<0.05). CTP improved endothelial function as evidenced by enhanced dilation to 10 µM adenosine diphosphate (change in diameter from baseline at: 36.2±1.0 vs 54.2± 5.3 µm, p<0.05). CTP increased resting pial artery perfusion (673±32 vs 750±201 laser Doppler units, p<0.05). These data suggests that while CTP does not affect cognitive abilities, it may contribute to increased baseline perfusion by enhancing dilation and reversing remodeling of MCAs.
Anti‐angiogenic anti‐tumor activity of BJ‐1301, an α‐tocopherol analog (842.5)
Authors: Banskota Suhrid , Chandra Regmi Sushil , Gautam Jaya , Ku Jin‐Mo , Nam Tae‐gyu , Jeong Byeong‐Seon , Kim Jung‐Ae
Published: June 2021

Because reactive oxygen species (ROS) are generated upon activation of growth factor receptors including VEGFR, and direct application of ROS induces angiogenesis, many natural and synthetic antioxidants including vitamin E were examined and found to have a certain level of antiangiogenic activity. In the present study, we observed that a synthetic aminopyridinol antioxidant, BJ‐1301, inhibits vascular endothelial growth factor (VEGF)‐induced angiogenesis in the growing chick embryo chorioallantoic membrane (CAM), and tumor growth on CAM xenografted with A549 human lung cancer cells. The inhibitory effects of BJ‐1301 were more potent than those of natural and synthetic counterparts, α‐tocopherol (α‐TOH) and 2,2,5,7,8‐pentamethyl‐6‐hydroxychroman (PMC), as well as SU4312, a VEGF receptor tyrosine kinase inhibitor. BJ‐1301 also inhibited ROS generation by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), a direct activator of NADPH oxidase with greater potency than α‐TOH and PMC, and a similar potency trend was observed for their antiangiogenic activities in vivo as well as in vitro (BJ‐1301 > PMC > α‐TOH). Together, these results suggest that BJ‐1301, the aminopyridinol analog of α‐TOH, induces stronger inhibition of both angiogenesis and tumor growth than α‐TOH, PMC, or SU4312 by targeting NADPH oxidase.

Grant Funding Source: This work was supported by the Basic Science Research Program through the National Research Foundati
Regulation of hypoxia inducible factors by Sprouty2 (842.9)
Authors: Hicks Kristin , Patel Tarun
Published: June 2021

Sprouty2 (Spry2) is an inhibitor of receptor tyrosine kinase signaling. Spry2 levels are decreased in cancers of the breast, lung, prostate and liver, thereby permitting excessive receptor tyrosine kinase signaling in these pathologies. Furthermore, a decrease in Spry2 levels has been correlated with poor patient prognosis. In development and tumor growth, cells experience a hypoxic environment to which they adapt to by up regulating the transcription factors, Hypoxia Inducible Factors (HIFs). The HIFs are composed of a beta subunit (HIF1β or aryl hydrocarbon nuclear translocator (ARNT)) and an oxygen sensitive alpha subunit (HIF1α or HIF2α). Using a hepatocellular carcinoma cell line (HuH7), we have shown that Spry2 decreases the protein levels of HIF1α, HIF2α, and ARNT without altering the mRNA levels. Additionally, Spry2 reduces the ability of the HIFs to induce transcription as measured by luciferase assays and mRNA levels of their target genes. We also show that Spry2 interacts with HIF1α and ARNT and that Spry2 decreases the stability of ARNT and HIF1α. To begin to deduce the mechanism, we have shown that Spry2 enhances the ubiquitination of HIF1α. Collectively, our data reveal a novel regulation of the HIFs by Spry2.

Grant Funding Source: Supported in part by NIH grant GM 073181
Coincident intracellular calcium rise is essential for Gi/o‐mediated activation of TRPC4 (843.3)
Authors: Thakur Dhananjay , Zhu Michael
Published: June 2021

TRPC4 is a member of the Canonical Transient Receptor Potential family of non‐selective cation channels. Na+ and Ca2+ influx through the active TRPC4 channel elicits membrane depolarization and intracellular Ca2+ signaling in various cell types including neurons, vascular endothelium and smooth muscle cells. It has been well‐established that homomeric TRPC4 channels are synergistically activated by co‐stimulation of two separate G protein pathways, Gq/11 and Gi/o. However, it remains unclear which step(s) or constituent(s) of the Gq/11 pathway is(are) essential for synergizing with Gi/o proteins to maximally activate TRPC4 channels. Using patch‐clamp recordings and fluorescence membrane potential measurements in HEK293 cells heterologously coexpressing mouse TRPC4β and Gi/o‐coupled µ opioid receptor, we have identified intracellular Ca2+ rise as the primary event associated with Gq/11 activation that synergizes with Gi/o stimulation to elicit maximal TRPC4 current. We also show that a signification portion of this effect is independent of calmodulin although Ca2+‐calmodulin can enhance channel activation. Our experiments demonstrate the contribution of phosphoinositide hydrolysis and IP3 receptors but rule them out as essential players. These findings argue for a critical role of intracellular Ca2+ rise in TRPC4 activation by Gi/o‐coupled receptors and illustrate the key requirements that support TRPC4 as a coincidence sensor of multiple signaling pathways.

Grant Funding Source: American Heart Association