bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost‐benefit beliefs as predictors of behavior: a longitudinal study of fruit and vegetable intake and physical activity (810.13)
Authors: Galloway Joy , Nigg Claudio , Banna Jinan
Published: June 2021

Positive health practices coexist across different behaviors, but it is unknown if predictors of change in one health behavior may also predict change in another behavior. This study investigates the relationship between pros/cons and fruit and vegetable (FV) intake and physical activity (PA) across two consecutive 6‐month intervals in a multiethnic adult population in Hawaii (n=434; mean age=49.3 ±16.7; BMI=26.1 ±5.9). Questionnaires assessed PA and FV pros/cons on a 5‐pt scale, PA (MET‐min/wk, Godin Leisure‐Time Exercise Questionnaire), and FV intake (servings/day, National Cancer Institute FV screener). Sample had mean FV=3.28 ±1.62; PA=3883 ±3711 MET‐min/wk; FV pro=4.1 ±0.9; FV con=1.9 ±0.9; PA pro=4.1 ±0.9; PA con=1.7 ±0.8. Regressions revealed that baseline FV pros were predictive of FV intake at 6 and 12mo follow‐up (p<0.01; p<0.05). Baseline PA pros were predictive of PA at 6mo (p<0.01) but not at 12mo. FV and PA cons were not predictive. Cross behavior predictions revealed a significant effect of PA pros on FV intake and of FV pros on PA at both 6 and 12mo (p<0.05). Controlling for baseline FV pros, change in FV pros from baseline to 6mo predicted both FV and PA at 6mo but not at 12. Change in PA pros, controlling for baseline PA pros, showed no significant effect on PA or FV at either interval. Having higher FV pros and increasing FV pros may have a beneficial effect on FV and on PA, indicating that these motivations may have a gateway effect on other behaviors.
Ready to eat cereal consumption with total and cause‐specific mortality: prospective analysis of 367,442 individuals (810.20)
Authors: Qi Lu , Xu Min , Lee Albert , Cho Susan
Published: June 2021

Background □ Intakes of ready to eat cereals (RTEC) have been inversely associated with the risk factors of chronic diseases such as cardiovascular disease (CVD), diabetes, and certain cancers; however their relations with total and cause‐specific mortality remain unclear. We prospectively assessed the associations of RTEC intakes with all causes and disease‐specific mortality risk.

Methods and Results □ The study included 367,442 participants from the prospective NIH‐AARP Diet and Health Study. Intakes of RTEC were assessed at baseline. Over an average of 14 years of follow‐up, in total 46,067 deaths were documented. Consumption of RTEC was inversely associated with risk of mortality from all‐cause mortality and death from cancer, digestive cancer, CVD, and respiratory disease. In multivariable models, as compared with non‐consumers of RTEC, those in the highest intake of RTEC had a 15% lower risk of all‐cause mortality and 10‐30% lower risk of disease‐specific mortality such as deaths from CVD, diabetes, all cancers, and digestive caner (all P for trend < 0.05). Within RTEC consumers, total fiber intakes were associated with reduced risk of mortality from all‐cause mortality (15%) and deaths from CVD (12%), cancer (10%), digestive cancer (17%), and respiratory disease (10%).

Conclusions □ Intakes of RTEC were inversely associated all‐cause mortality and disease‐specific mortality; Within RTEC consumers, higher intake of total fiber was associated with reduced risk of total and cause‐specific mortality.
Psychometric properties and validation of an instrument to measure perception of well‐being associated with water intake (IPBA) (810.33)
Authors: Monterrubio Eric , Espinosa Juan , Sánchez Marcela , Barquera Simón
Published: June 2021

The IPBA was developed from a qualitative study and validated by an expert panel to measure perceived physical and mental welfare associated to hydration using 56 items and 2 dimensions: Physical (PW) and Mental (MW) Wellness. The objective of this analysis was to validate this instrument in adults of low socioeconomic status from Cuernavaca, Mexico.

The IPBA was applied to participants of an intervention study (Clinical Trial: NCT01982981). We used Cronbach's alpha (CA) and conducted Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). A score was constructed with items from the final model and was associated with total liquids intake using a regression model.

A total of 676 participants were included in the EFA. We identified two dimensions with 10 items each, the CA was 0.82 and 0.85 respectively, and the factor loadings over 0.45. In the CFA, 412 participants were included; the global CA was 0.844 (PW= 0.80; MW=0.79). Robust estimates of the model were satisfactory: Satorra‐Bentler test=115.4 (p=0.34), CFI=0.99 and RMSEA=0.011. In the final model 17 items were included achieving a maximum score of 68 and a minimum of zero. The welfare score was associated to liquid intake (0.85, p = 0.005).

The IPBA is able to quantify the perception of welfare associated with hydration.
Association of marijuana use with oxidative stress and antioxidant nutrients in HIV+ adults on antiretroviral therapy (810.34)
Authors: Vraney Joy , Stewart Tiffanie , Campa Adriana , Greer Pedro , Li Yinghui , Martinez Sabrina , Baum Marianna
Published: June 2021

Objective: To assess the effect of marijuana (MJ) use on oxidative stress and antioxidant intake in 201 HIV+ adults with a high exposure to MJ.

Methods: Plasma oxidized glutathione and 8‐oxo‐dG were collected. Intakes of Vitamins A, E and C, carotenoids, Selenium, and Zinc were assessed by 24‐hour recalls.

Results: Mean age was 45.2±8.1 years and 27% used MJ. Users were significantly younger than non‐users (42 vs. 46 years, p<0.01). There were no significant differences between MJ users and non‐users in markers of oxidative stress, although the mean oxidative stress was well above the mean for the general population and the mean antioxidant intakes were all under the RDAs.

Conclusions: In HIV+ adults, there were no differences in markers of oxidative stress and antioxidant intakes between MJ users and non‐users, probably due to the high levels of oxidative stress and low antioxidant intakes in this population, showing that this population may benefit from antioxidant supplementation. MJ use is still controversial, and our findings were limited by small sample size. More controlled research is needed to assess advantages and disadvantages of MJ use in this population with a high rate of exposure.

Grant Funding Source: NIDA and NIAAA
Effect of heat stress on expression of amino acid and glucose transporters in pigs (816.4)
Authors: Cota Margarita , Arce Néstor , Castillo Gilberto , Araiza Benedicto , Cervantes Miguel , Morales Adriana
Published: June 2021

Animals exposed to high ambient temperatures (AT) suffer from heat stress (HS), which provokes physiological and metabolic changes. HS seems to affect the gastro intestinal tract integrity hence affecting absorption capacity. An experiment was conducted with 18 pigs (32.4±2.7 kg BW) to examine the effect of natural severe HS (AT up to 45 °C) on expression of amino acid (b0,+, CAT1) and glucose (SLC2A1, GLUT4) transporters in duodenum, jejunum, liver, and Longisimus (LDM) and Semitendinosus (STM) muscles. Treatments (T) were: T1, comfort pigs housed in AT controlled room (22±2 °C) and fed ad libitum (C‐AL); T2, pigs housed as in T1, but feed‐restricted (C‐FR); T3, pigs housed in a room with no climate control (AT raised up to 45 °C; HS). HS pigs consumed about 95% of their ad libitum feed intake, and feed intake of C‐FR was similar to that of HS pigs. All pigs received the same diet and purified water. HS increased relative expression of CAT‐1 (P=0.043) in liver, but reduced it in LDM (P=0.007). HS increased duodenal expression of SLC2A1 (P=0.041), and that of GLUT4 (P=0.063) in STM. Severe HS affects the expression of glucose and amino acid transporters in selected pig tissues.

Grant Funding Source: Supported by CONACYT‐México
Zinc‐regulated gene expression in Schizosaccharomyces pombe (818.4)
Authors: Liu Yi‐Hsuan , Choi Sang Yong , Corkins Mark , Bird Amanda
Published: June 2021

Zinc is essential for all life. In the human body, zinc is a cofactor in a large number of enzymes and regulatory factors, and can act as a signaling molecule. Although zinc is essential for life, in excess it can be toxic. As a consequence, it is important to understand how cells maintain zinc homeostasis. We use the fission yeast, Schizosaccharomyces pombe, as a model system to study the mechanisms of how cells sense and regulate intracellular zinc levels. We have identified a protein called Loz1 (Loss of Zinc sensing) that inhibits target gene expression in zinc‐replete cells. Here we have used RNA‐seq to identify Loz1 target genes. Our results reveal new transporter families, regulatory factors, and enzymes that are regulated by Loz1, and provide insight into the metabolic pathways and processes that are directly regulated by zinc at a cellular level.
‘Raw Materials’ in tissue engineering (82.1)
Authors: Detamore Michael
Published: June 2021

My group is interested in new technologies and strategies for osteochondral tissue regeneration. Some of the core tenets of our philosophy for tissue regeneration include the use of “raw materials” as building blocks, the engineering of continuous gradients, and leveraging osteochondral tissue engineering to enhance cartilage regeneration. The use of scaffolds built exclusively from microspheres provides a means for both raw materials and gradients to be employed in osteochondral tissue engineering. With the use of microspheres, we have shown that a single osteochondral biomaterial implant can be created with a continuous gradient in both material composition and growth factor release, with a seamless transition from one side to the other. A series of in vivo tests in both the knee and in the temporomandibular joint (TMJ, or jaw joint) have yielded promising results for the use of microsphere‐based scaffolds. As an alternate strategy, we are pioneering the use of interpenetrating network (IPN) hydrogels to encapsulate cells for cartilage tissue engineering. We have shown that two different hydrogel networks can be combined in such a way to create an IPN hydrogel with mechanical integrity far superior to either of the original gels, with viable cells encapsulated. This IPN approach has been further enhanced with the incorporation of “raw materials” for cartilage.
Tissue‐engineered extracellular matrices for 3D tissue modeling and clinical applications (82.2)
Authors: Germain Lucie
Published: June 2021

Extracellular matrices (ECMs) are a key component of the tissue structure and influence cell responses and organ functionality. At the LOEX centre from Laval University, the self‐assembly approach for tissue engineering was designed to elaborate complex living substitutes based on the ability of cells to produce and organize their own extracellular matrices. Various tissues have been produced such as skin, cornea, blood vessels, etc without exogenous ECM or scaffolds. These natural ECMs favor the preservation of stem cells, facilitate vascularization and innervation, and provides adequate mechanical properties to these living three‐dimensional constructs. Moreover, this technique allows the fabrication of autologous substitutes. Tissue‐engineered skin, comprising a dermis and an epidermis, provides a permanent autologous graft for severely burned patients. No significant contraction was observed in vivo after grafting these tissue‐engineered skin substitutes. The presence of the ECMs promoted a good healing and suppleness after grafting. Thus, natural ECMs can be produced in vitro to generate tissue‐engineered substitutes for in vitro studies and clinical applications.

Supported by the Canadian Institutes for Health Research (CIHR), Fonds de Recherche du Québec en Santé (FRQS), and the Cell and Tissue Therapy Network of the FRQS. LG is holder of the Chair on Stem Cells and Tissue Engineering.
Pottenger's cats revisited: a classic example of a nutritional deficiency of taurine (820.4)
Authors: Davidson Robert , Emlet Jonathan
Published: June 2021

Objective. From 1932 to 1942, Dr. Francis Marion Pottenger Jr. conducted a group of experiments to determine the effects of heat‐processed food on cats. Cats fed an all‐raw diet were healthy while cats fed the cooked meat diet developed various health problems. At the time of Pottenger's studies the heat labile amino acid taurine had not yet been identified as essential for cats. This work shows that the deficiencies Pottenger identified in cats correspond with those of a taurine deficiency and are the direct result of the lack of taurine in the feline diet.

Methods. Pub Med and EBSCO Host were utilized to obtain journal articles. The Pottenger papers were obtained from the Price‐Pottenger Nutritional Foundation. The physiological effects of a cooked diet described by Pottenger in his papers were compared with data from recent studies on taurine deficiency in the feline diet.

Results. Pottenger’s main observations of near and far sightedness, cardiac leasions, increased stillbirth, low birthweight, poor kitten survival, and developmental abnormalities each correspond to published descriptions of taurine deficiency in cats with multiple references for each described condition.

Conclusions. Taurine deficiency is a strong explanation for the symptoms observed by Pottenger in his cat studies. Pottenger’s own conclusion that there was an ‘as yet unidentified, heat‐labile protein factor’ is realized in taurine.
LDL fraction in rats‐fed trans fatty acids induces inflammatory factors in human umbilical vein endothelial cells (821.1)
Authors: Chiba Shun , Hara Hiroshi
Published: June 2021

Trans‐fatty acid is a well‐known risk factor of atherogenesis, however its mechanism has not been clarified. Plasmalogen is a subclass of phospholipids, characterized by vinyl‐ether bond in sn‐1 position, and known to have the anti‐atherogenenic property. We have found that trans‐fatty acids were incorporated into sn‐1 position of plasmalogen (trans‐type plasmalogen) in trans‐fatty acids fed rats. The aim of this study was to examine the physiological effects of trans‐type plasmalogen on vascular endothelium. Wistar‐ST male rats were fed an AIN‐93G based diet with or without 23% hydrogenated rape seed oil (including 40% trans‐fatty acids) for 8 weeks, and then we prepared LDL fraction from their aorta blood. Human Umbilical Vein Endothelial Cells (HUVEC, p=4~6) were cultivated until the cells were 80% confluent and the medium was changed containing rat LDL, then HUVEC were cultivated for 24h. The gene expressions of ICAM1, VCAM1 and MCP1 in HUVEC were increased in trans LDL group (LDL including trans‐type plasmalogen) more than control LDL group. MCP1 protein in cell supernatant was also higher in the trans group. These results suggest that LDL including trans‐type plasmalogen has inflammatory effects in HUVEC. We should clarify that trans‐type plasmalogens actually contribute the inflammatory effects in LDL on HUVEC.
Role of ACOT1 in hepatic lipid trafficking (821.6)
Authors: Franklin Mallory , Sathyanarayan Aishwarya , Mashek Mara , Mashek Douglas
Published: June 2021

Peroxisome proliferator‐activated regulator alpha (PPARα) is a major regulator of fasting lipid metabolism. PPARα induces transcription of cytosolic Acyl‐CoA Thioesterase 1 (ACOT1), which hydrolyzes acyl‐CoAs into long‐chain free fatty acids and Coenzyme A. However, the physiological role of ACOT1 in lipid metabolism is not known. Thus, the objective of this research was to determine the contribution of hepatic ACOT1 to lipid metabolism and signaling. To test our objectives, we injected C57/Bl6 mice with an adenovirus harboring shRNA targeted to ACOT1 or a scrambled control. One week post‐injection, mice were fasted overnight and sacrificed. Compared to control mice, ACOT1 knockdown resulted in an increase in serum β‐hydroxybutyrate, a marker of fatty acid oxidation, and an increase in serum triglyceride, indicating a possible increase in very‐low density lipoprotein secretion. These changes were not accompanied by a significant change in liver triglyceride. In addition, genes involved in mitochondrial biogenesis were decreased in response to ACOT1 knockdown suggesting that ACOT1 alters cell signaling to influence gene expression. In summary, these results show that ACOT1 plays an important role in regulating hepatic lipid metabolism and may serve an important novel role in trafficking of lipids to influence cell signaling.
High protein diets enhance glycemic regulation during energy restriction: a comparative analysis of milk‐ and soy‐based diets (823.1)
Authors: Lin Gregory , Murphy Nancy , Gaffney‐Stomberg Erin , Young Andrew , McClung James , Pasiakos Stefan
Published: June 2021

Consuming high protein during energy restriction (ER) promotes glycemic control. However, the extent to which protein source modulates the glycemic response and the intracellular mechanisms by which hepatic regulation of blood glucose is maintained during ER is not well described. Eighty male Sprague‐Dawley rats (12 weeks old) were randomly divided into 8 treatment groups and fed energy adequate (EA) or ER (60% of the ad libitum feed intake for EA) diets containing two levels (control: CP, 10%; and high protein: HP, 35%) and sources (milk protein concentrate: MPC; and low isoflavone soy concentrate: SOY) of protein for 16 weeks. Fasting serum insulin and glucose concentrations were assessed, and hepatic regulators of gluconeogenesis were analyzed using Western blot. Blood glucose was similar across groups (group mean ± SD, 109 ± 11 mg/dL, P > 0.05). However, insulin levels were lower (P < 0.05) for HP (162 ± 63 pmol/L) than CP (208 ± 80 pmol/L); ER (165 ± 65 pmol/L) than EA (204 ± 80 pmol/L); and MPC (160 ± 66 pmol/L) than SOY (208 ± 75 pmol/L). Independent of protein source and energy status, glucose‐6‐phosphatase, phosphoenolpyruvate carboxykinase, and hepatic nuclear factor‐1α total protein content were higher (P < 0.05) for HP than CP. These data confirm the gluconeogenic advantage conferred by consuming a HP diet and suggest that a milk‐based diet may further enhance glycemic control by increasing insulin sensitivity.

Grant Funding Source: Supported by Dairy Research Institute and USAMRMC
Association between vegetarian diets and bone health (823.2)
Authors: Knurick Jessica , Johnston Carol , Wherry Sarah
Published: June 2021

Low bone mineral density (BMD) is associated with an increased risk of osteoporotic fracture, and diet is considered an important modifiable risk factor linked to bone health. While vegetarian diets appear to exhibit health advantages, there is conflicting evidence regarding the effect of these diets on long‐term bone health. Purpose: To compare dietary composition, protein status, and bone health in long‐term omnivores (OMN) and vegetarians (VEG). Methods: Dietary intake and 24‐hour urine was examined in healthy OMN (n=23) and VEG (n=46), aged 19‐50 years (30.3 ± 8.0 y). Dietary status ranged from one‐year to lifetime adherence. Each subject completed a 24‐hour recall, administered by a trained nutritionist, to assess dietary intake and completed a 24‐hour urine collection. Urinary nitrogen and calcium were measured in 24‐hour urine with colorimetric enzymatic assays. After testing for normality, univariate analyses of total body BMD z‐scores were controlled for body weight. Independent samples T‐tests were used on all remaining variables. Results: BMD z‐score was significantly lower in the VEG group (p=0.028), which was associated with protein status (p=0.49). VEG diets also exhibited lower urinary nitrogen (p<0.001) and lower urinary calcium (p=0.008) levels than OMN diets. Conclusion: VEG diets were associated with decreased protein intake, urinary nitrogen, and urinary calcium. These factors may contribute to the low bone mineral densities observed in the VEG group. These data suggest that VEG diets, marked by inferior protein and calcium statuses, may pose a risk to bone health.
Plasma and breast milk biotin concentrations decrease in lactating women consuming a dietary biotin intake exceeding current recommendations (827.10)
Authors: Perry Cydne , West Allyson , Yan Jian , Jiang Xinyin , Malysheva Olga , Caudill Marie
Published: June 2021

Biotin is a water‐soluble B vitamin with many key roles in human metabolism. As a cofactor for several carboxylation reactions, biotin is required for gluconeogenesis, fatty acid synthesis, and leucine catabolism. Biotin may also interact with histones to affect genome expression. The dietary requirement for biotin is unknown. Thus, recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30μg/d and for lactating women, 35μg/d. As part of a controlled feeding study, healthy pregnant (n=26, 27wk gestation), lactating (n=28, 5wk postpartum), and control (non‐pregnant, non‐lactating; n=21) women consumed ~60μg dietary biotin/d for 10‐12 weeks. Plasma and breast milk samples were collected and biotin was measured at baseline (wk 0) and study end (wk 10 or 12). Plasma biotin was measured via ELISA kit and breast milk biotin was measured via LCMS. Throughout the study, the response of plasma biotin varied by reproductive group (P = 0.05). Among pregnant (P=0.65) and control (P=0.88) women, plasma biotin did not change from baseline (pregnant: 130ng/L (105, 161); control: 143ng/L (113, 180)) to study end (pregnant: 137ng/L (111, 170); control: 146ng/L (115, 184)). However, among lactating women, plasma biotin decreased (P < 0.01) from baseline (193ng/L (157, 237)) to study end (136ng/L (111, 167)) as did breast milk biotin concentrations (P = 0.02; baseline: 12pM/mL (8.2, 16.5); study end: 7pM/mL (4.8, 9.7)). In addition, plasma and breast milk biotin concentrations were correlated (rho=0.501; P< 0.001). These results indicate that plasma biotin may be a biomarker for breast milk biotin and that lactating women may benefit from a dietary biotin intake that exceeds the study dose of 60μg/d. Data presented as means and 95% confidence intervals.

Grant Funding Source: Support:The Hartwell Foundation,The Gerber Foundation,NIH R03 HD065962‐01A1,Shepherd Univ Foundation
Chromium 3+ as a therapy for diabetes type 2 (828.1)
Authors: Harland Barbara , Oberleas Donald
Published: June 2021

Chromium in the +3 oxidative state is an essential and important form metabolically Chromium forms very stable complexes with water (5 x 10‐7 M‐1s‐1), urea, ammonia, halides, sulfate and organic acids. Chromium's major function is in proper glucose utilization by establishing stable complexes with glutamic acid residues in insulin, in a chaperone located between the insulin and insulin receptor. The insulin receptor will open a glucose channel in the cell membrane and thus allow the glucose to enter the cell to be metabolized by glycolysis. Only small amounts of chromium are required, less than 1 % of dietary chromium is absorbed and retained. The chaperone has been isolated from liver and kidney of several mammalian species and bovine colostrum. The chaperone is composed of glycine, cysteine, aspartate and glutamate in a molar ratio of 2:2:2:4 and has a molecular weight of ~1500.

The combination of insulin, chaperone and insulin receptor are the functional aspects of the receptor. Chaperone and insulin require stability for activation of tyrosine kinase for the process of providing the means to transport glucose into the metabolic cells for metabolism to energy and the provision of carbon segments for other metabolic entities. Though the number of human test subjects is small, it has been demonstrated that Diabetes Type 2 can be effectively treated as a chromium deficiency.
Quercetin and red onion extract attenuate high fat diet‐induced insulin resistance while increasing energy expenditure and skeletal muscle mitochondrial number despite a decrease in Pgc1a (829.1)
Authors: Henagan Tara , Stewart Laura , Ribnicky David , Noland Robert , Forney Laura , Gettys Thomas , Cefalu William
Published: June 2021

Quercetin (Q), a bioflavonoid abundant in onions, attenuates the development of insulin resistance (IR) and increases expression of the transcriptional coactivator, peroxisome proliferator‐activated receptor gamma coactivator‐1 alpha (PGC1α). We investigated the effects of Q and Q‐rich red onion extract (RO) on ameliorating high fat diet (HFD)‐induced IR and altering skeletal muscle Pgc1a expression and mitochondrial biogenesis. 9wks of Q and RO supplementation on a 45% HFD decreased adiposity (P<0.05) in C57BL6/J mice and increased energy expenditure (P<0.05) compared to HFD‐fed mice. Q and RO mice exhibited increased insulin sensitivity (P<0.05) and muscle mitochondrial number (P<0.05). Pgc1a gene expression was decreased in Q (P<0.01) and RO (P<0.05) groups. In direct contradiction to the 9wk Q‐ and RO‐induced decreases in the present study, we previously found that Q significantly increased Pgc1a after 8wks of supplementation, suggesting that (1) Q and RO may mediate their effects on mitochondrial adaptation independent of changes in Pgc1a or (2) Q‐ and RO‐induced increases in Pgc1a are necessary for establishing but not sustaining mitochondrial adaptation. We conclude that dietary Q and RO supplementation ameliorate HFD‐induced obesity and prevent IR by increasing energy expenditure and skeletal muscle mitochondrial number.

Grant Funding Source: Supported by NIH 5T32‐DK064584‐09, 5P50‐AT002776‐09, 8P20‐GM103528‐07 and 5P30‐DK072476‐07 grants.
Alpha‐lipoic acid reduces LDL‐particle number and PCSK9 concentrations in high‐fat fed obese Zucker rats (829.14)
Authors: Rideout Todd , Carrier Bradley , Wen Shin , Zigouras Sophia
Published: June 2021

Alpha‐lipoic acid (LA) possesses hypocholesterolemic properties; however, the underlying molecular mechanisms have not been fully elucidated. We examined the effects of LA supplementation on blood cholesterol, lipoprotein distribution, and hepatic cholesterol homeostasis in a high fat fed Zucker rat model driven by both a genetic predisposition and diet induction toward obesity and dyslipidemia. Rats (n=8) were assigned to a high fat (HF) diet or the HF diet with 0.25% LA (HF‐LA) for 30 days. LA‐supplementation protected against diet‐induced obesity (102.5±3.1 vs. 121.5± 3.6, % change BW), reduced plasma total‐C (11%), non‐HDL‐C (25%) and LDL particle number (46%) and increased HDL particle number (22%) compared with the HF group. Hepatic cholesterol concentration did not differ between the HF and HF‐LA groups. LA supplementation reduced the mRNA expression of HMG‐CoAr (0.7 fold of HF) and enhanced the protein abundance of LDLr (2 fold of HF) and nuclear SREBP2 (3 fold of HF). LA supplementation was also associated with a reduction in hepatic PCSK9 mRNA (0.5 fold of HF) and serum PCSK9 concentration (70%), a primary regulator of LDLr turnover. Study results suggest that LA supplementation protects against hypercholesterolemia through a mechanism that involves modulation of PCSK9 activity and hepatic LDL‐C clearance.

Grant Funding Source: Supported by a grant from the National Center for Complementary and Alternative Medicine
Workshop: how to include ultrasound in your anatomy course (83.1)
Authors: Guttmann Geoffrey
Published: June 2021

Attendees will be introduced to the principles of ultrasound, the ultrasound machine and probes, and some approaches to applying ultrasound imaging in the anatomy lab. Attendees will have an opportunity to use ultrasound to obtain images relevant to the thyroid, wrist, liver and gallbladder, which would give one experience with the common probes being used in ultrasound clinics. A demonstration will precede the ultrasound activity. Attendees will work in groups and use the ultrasound machine on each other. There will also be a demonstration of musculoskeletal ultrasound imaging of the upper limb (rotator cuff muscles) to demonstrate the relevance of ultrasound to illustrate the rotator cuff muscles and their function. The last part of this activity will be to view the heart on a live model. A live model will be available.
Scavenging of toxic α‐dicarbonyls and α,β‐unsaturated aldehydes using polyphenol phytochemicals: reactivity studies and adduct identification (830.10)
Authors: Gu Liwei , Wang Wei , Liu Haiyan
Published: June 2021

Reactive toxic carbonyls include α‐dicarbonyls (e.g. glyoxal & methylglyoxal) and α,β‐unsaturated aldehydes (e.g. malondialdehyde & acrolein). These compounds react with proteins to form the Advanced Glycation End‐products (AGEs) in vivo, contributing to aging, diabetic complications, and other chronic diseases. The objective of this study was to investigate the efficacy of selected polyphenol phytochemicals in scavenging reactive carbonyls and identify phytochemical‐carbonyl adducts. Resveratrol, quercetin, (+)‐Catechin, (‐)‐epicatechin, and chlorogenic acid reacted with glyoxal, methylglyoxal, malondialdehyde, or acrolein in pH 7.4 phosphate buffer for 48 hours. Phytochemicals and carbonyl compounds were quantified during the reaction and empirical degradation half‐time was calculated. Results showed that resveratrol, catechin, and epicatechin were more efficient in scavenging carbonyls than quercetin and chlorogenic acid. Malondialdehyde had the least reactivity towards phytochemicals compared with other carbonyls. Polyphenol carbonyl reaction gave rise to various adducts. A number of adducts were detected and their structures were tentatively identified using HPLC‐ESI‐MSn. Results of this study showed that polyphenols and carbonyl compounds reacted with different velocities and generated adducts, providing insight to the health benefits of polyphenols.
Antioxidant activity of Phellinus igniarius extracts (830.32)
Authors: Liu Fan , Liao Sentai , Zou Yuxiao , Xiao Gengsheng
Published: June 2021

Phellinus igniarius, widely distributed in eastern Asia, has long been used in folkloric and traditional medicine especially in China to increasing immunity and resistance to tumor. The aim of the present study was screening antioxidant activity of the methanolic extract and its fractions (petroleum ether, ethyl acetate, n‐butanol and water) of the fruit body of Phellinus igniarius. In this study, the in vitro antioxidant activities of these extracts were evaluated by ferric reducing antioxidant power (FRAP), hydroxyl radical scavenging activity (HSA) and DPPH radical scavenging activity assays. The total phenolics (TP) and flavanoids (TFA) were also measured. The results indicated that almost all extracts performed well in all assays of antioxidant capacity. In the HSA assay, extracts of Phellinus igniarius all displayed high antioxidant activity. In the DPPH radical scavenging assay and FRAP assay, the ethyl acetate and n‐butanol fraction displayed higher activity than petroleum ether and water fraction. Most antioxidant performance indicators (FRAP, HAS, DPPH) correlated well with the TP and TFA content of the extracts, reflecting a higher involvement of these compounds in antioxidant processes.On the other hand, the n‐butanol fraction contained average amounts of polyphenols but ranked first in the majority of the tests, indicating the occurrence of particularly efficient compounds with very important antioxidant properties.

Grant Funding Source: Supported by the Foundation of President of Guangdong Academy of Agricultural Sciences (No. 201006)
Macrophage migration inhibitory factor increases vascular permeability through autophagy formation (832.3)
Authors: Yeh Trai‐Ming , Chen Hong‐Ru
Published: June 2021

Vascular hyperpermeability is an early pathogenic change in acute inflammatory shock. The high mortality rate of shock patients suggest our understanding of the molecular mechanisms to cause vascular hyperpermeability is not enough. Macrophage migration inhibitory factor (MIF) is a pro‐inflammatory cytokine that plays important roles in many different forms of shock. In the past we found recombinant MIF can induce vascular leakage in mice and induce autophagy in cells. However, little is known whether autophagy is involved in MIF‐induced vascular hyperpermeability. Here, we demonstrated that the permeability of human endothelial cell line HMEC‐1 cells was increased in the presence of MIF in a dose‐and time‐dependent manner. In addition, the permeability of HMEC‐1 cell increased by MIF was inhibited in the presence of MIF inhibitor (ISO‐1) as well as ROS scavenger N‐acetyl‐L‐cysteine (NAC) or PI3K inhibitor (3‐MA), indicating autophagy formation is involved in MIF‐induced hyperpermeability of HMEC‐1 cells. Furthermore, western blot analysis of HMEC‐1 cell lysate confirmed that MIF promoted LC3 conversion, together with activation of autophagy upstream signal pathway. Taken together, these results suggest, in addition to block MIF, blocking autophagy formation by its inhibitors may provide potential therapeutic approaches against shock.
A possible cell surface mechanism for magnesium sulfate's antithrombocytic activity (833.1)
Authors: Zem Gregory , Arvizu S. , Ter‐Papyan H. , Sadeghi H. , Hovsepian G. , Hambarsoomian A. , Evans A. , Chavez C. , Tivriktsyan A. , Tortorice C.. , Ohanessian K. , Orujyan A. , Irikyan C.. , Molina D. , Behshadpour A. , Markosian S. , Boyadjian Z. , Salas N. , Basmajian M. , Aminian P. , Patel K. , Haritounian A. , Kurginyan A. , Sheikhpoor B. , Sarkissian L. , Tosunyan O. , Simidyan A. , Mikaelyan H. , Bardo M. , Simonyan K. , Yahya‐Kashani D. , Labson K. , Asatryan M. , Gyurgchyan T. , Oppenheimer S.
Published: June 2021

MgS04 suppresses platelet aggregation (Brit J Hematol 119: 1033, 2002; Circulation 105: 1970, 2002; Magnes Res 18: 7, 2005; J Matern Fetal Neonat Med: 478, 2012). Intracellular metabolic mechanisms have been proposed to cause this suppression. Here we show, using a simple, inexpensive quantitative assay (FASEB J 27: abs 341, 2013) that MgSO4 disaggregates fixed cells in a yeast (Saccharomyces cerevisiae) model. In 1715 separate experiments by 35 independent investigators, MgSO4 (3mg/slide droplet) increased percent of fixed single cells by 60 min by an average of 17% to as much as 33% (with p values often less than 0.05 compared to controls without reagent), while alpha methyl glucose, D‐glucose and D‐mannitol decreased percent single cells by an average of 15%. It remains to be determined if MgSO4 can unclump fixed platelets, implicating a cell surface mechanism in its antithrombocytic activity. MgSO4 may be a useful anticlumping agent in many applications (Science 341: 186, 2013). Anti‐infection, anti‐biofilm, and anti‐cancer reagents could be identified using this simple, inexpensive, quantitative assay system (Supported by university incentives and grants from NIH RISE, SCORE, Sidney Stern Memorial Trust, Joseph Drown Fdn and NSF Presidential Award 0731633).
Synthetic melanin polymers with antithrombotic activity (833.3)
Authors: Holmes Earle
Published: June 2021

I evaluated the anticoagulant properties of a family of novel water soluble melanin polymers (Mels) synthesized by a patented process (12/809,369). Mels were screened for activity in standard assays for the measurement of the PT, the aPTT and the TT. Active Mels were further investigated by the evaluation of the kinetics of fibrin polymerization and the re‐polymerization of fibrinopeptides, and for the direct inhibition of factors Xa and thrombin. Ten of the Mels prolonged the aPTT and the TT by more than 2‐ fold (aPTT: mean, 3.7‐fold, range, 2.1‐6.7; TT: mean, 8‐fold, range, 2.1‐15). Mels C1, C12, EM and CAM (2.5 to 41mcg/mL) caused dose‐dependent delays in the onset, rate, and extent of thrombin‐mediated fibrinogenesis in the presence and absence of Ca++. Mels C1 and C12 inhibited the re‐polymerization of fibrinopeptides at high doses, but increased the rate and extent of re‐polymerization at low doses. Mels minimally inhibited factor Xa activity in a chromogenic assay, whereas Mels C1, EM, and C12 inhibited the hydrolysis of a chromogenic thrombin substrate by 49%, 39%, and 28%, respectively. Mels inhibit the common pathway of coagulation by multiple mechanisms. These activities, in conjunction with the high chemical reactivity of the intermediates that are generated during Mel synthesis may provide a new approach to the incorporation anti‐thrombotic properties into biomaterials.
Acne in workers at the ferroalloy production (835.7)
Authors: Batpenova Gulnar , Kotlyarova Tatiyana , Tarkina Tatiyana , Dzhetpisbaeva Zulfiya
Published: June 2021

Enterprises of the ferroalloy production are characterized by a combination of adverse factors, such as chemical, physical, temperature differences, thermal radiation.

The aim of the study was to investigate the frequency and severity of acne definition of the employees at ferroalloy production. We have carried out a preventive medical examination of 2856 workers.

From 2856 examined workers, skin pathology is identified at 621 that was 21,7±0,8%, including acne ‐ 53 (18,5±2,3%). In a comparative analysis on groups of units higher incidence of acne was found in group 1 workers coming into contact with more intense dermotropic factors of production cycle 36 (67,9±6,4); Group II ‐ 10 patients (18,9±5,4); in III ‐ 7 people (13,2± 4,6). The severity was assessed by a simple three‐step scale: acne vulgaris I and II severity ‐ 43 (81,1±5,4%), severe degrees of acne ‐ 10 (18,9 ± 4,6%); including acne conglobate ‐ 3 (5,7±3,2%) and nodular ‐ cystic acne ‐ 7 (13,2 ± 4,6%). Severe forms of acne were to the employees I division. Patients with acne related mainly to the age group of 20‐29 years ‐ 34 people (64.1%) and 30‐39 years ‐ 19 people (35.9%). It was characterized by a more frequent development of the disease in up to 5 years ‐ 36 workers (67.9%), respectively.

Thus, acne is more prevalent in one group of workers are employed directly in the production of ferroalloys 36 (67,9±6,4).
Antiplatelet characteristics of Z4A5, a novel selective platelet glycoprotein IIb/IIIa inhibitor, under long‐term infusion (837.13)
Authors: Shin Xiaolian , Shen Xin , Jing Jing , Feng Meng , Wang Bing
Published: June 2021

Introduction:Glycoprotein IIb/IIIa inhibitors are important in the treatment of acute coronary syndromes (ACS) and percutaneous coronary interventions due to their effects on the final common pathway of platelet aggregation. Z4A5 is a new hexapeptide IIb/IIIa inhibitor with antiplatelet and antithrombotic effects. This study was performed to assess the stability of the antiplatelet effects and characteristics of Z4A5 with long‐term infusion. Materials and Methods:Light‐transmission aggregometry was used to measure platelet aggregation to assess the antiplatelet efficacy of Z4A5 in vitro and ex vivo. The activity of Z4A5against platelet aggregation and template bleeding time were evaluated after 8‐hour intravenous infusions in Beagle dogs following a 3 × 3 Latin square design. The recovery of platelet function after suppression by Z4A5 was compared with the recovery following eptifibatide and tirofiban administration 4h after termination. Results:Z4A5 completely inhibited Adenosine diphosphate (ADP)‐ and thrombin‐induced in vitro platelet aggregation with an IC50 of 265.8±22.9 nM and 180.3±58.2 nM. It also markedly and stably prevented ADP‐induced ex vivo platelet aggregation and prolonged the bleeding time throughout the 8‐hour infusion. Platelet function suppressed by long‐term infusion of Z4A5 recovered significantly faster than after eptifibatide infusion.Conclusions: Z4A5 has a stable antiplatelet effect and can be more readily controlled by physicians to monitor platelet function in ACS patients compared with two other GP IIb/IIIa inhibitors.

Grant Funding Source: Supported by the Ministry of Science and Technology New Drug Major Project (No. 2012ZX09103‐301‐039)
Protective effect of remote ischemic preconditioning by brief hind limb ischemia against the gastric mucosal injury caused by severe gastric ischemia‐reperfusion: participation of glucocorticoids (840.12)
Authors: Filaretova Ludmila , Komkova Olga , Morozova Olga , Bagaeva Tatiana
Published: June 2021

In the present study we investigated the effect of noninvasive hind limb ischemic preconditioning on the gastric mucosal injury caused by severe gastric ischemia‐reperfusion and participation of glucocorticoids in this effect. Under deep anesthesia rats were exposed to prolonged gastric ischemia‐reperfusion (30 min occlusion of celiac artery followed by 3 h of reperfusion) alone or with preliminary remote ischemic preconditioning (10 min hind limb ischemia, by placing a tourniquet on the proximal part of the limb, followed by 30 min of reperfusion). The participation of glucocorticoids was investigated by glucocorticoid receptor antagonist RU‐38486, inhibitor of glucocorticoids’ synthesis metyrapone, and adrenalectomy alone or with corticosterone replacement. The prolonged gastric ischemia‐reperfusion resulted in the gastric injury. In control animals limb remote ischemic preconditioning induced plasma corticosterone rise and attenuated the gastric injury caused by prolonged gastric ischemia‐reperfusion. In adrenalectomized rats without corticosterone replacement and in rats pretreated with metyrapone or RU38486 the gastroprotective effect of limb remote ischemic preconditioning was prevented. The results suggest that hind limb remote ischemic preconditioning attenuates gastric injury caused by severe ischemia‐reperfusion and glucocorticoids participate in the protective effect.

Grant Funding Source: Supported by grants from RFBR (N13‐04‐01680‐a); Programs of Presidium RAS 7P
Inhibition of the transient receptor potential melastatin‐2 ion channel in breast adenocarcinoma cells causes increased DNA damage and decreased proliferation (842.2)
Authors: Koh David , Hopkins Mandi , Liu Mengwei , Feng Xiaoxing
Published: June 2021

The transient receptor potential, melastatin‐2 (TRPM2) cation channel is known for facilitating cell death and is thus targeted for pharmacologic inhibition in debilitating diseases/conditions to decrease tissue injury and prevent cell death. The objective of this study was to determine the role of TRPM2 in breast cancer cells. TRPM2 function in MCF‐7 and MDA‐MB‐231 breast adenocarcinoma cells was investigated using TRPM2 pharmacologic inhibitors or RNAi silencing. In these cells, inhibition or knockdown of TRPM2 led to decreased proliferation and increased cell death after chemotherapeutic treatments. These effects were not observed after equivalent treatments in noncancerous breast cells. Cellular localization studies confirmed the plasma membrane/cytoplasmic localization of the TRPM2 ion channel in noncancerous breast cells. However, it exhibited a unique nuclear localization in breast adenocarcinoma cells. Investigation into a possible nuclear role for TRPM2 demonstrated that inhibition or RNAi silencing of TRPM2 in breast adenocarcinoma cells led to increased DNA damage and decreased genomic integrity as measured by Comet assay. Minimal effects on genomic integrity were observed in noncancerous breast cells after equivalent treatments. This data indicates that TRPM2 facilitates genomic integrity in breast adenocarcinoma cells. Taken together, these results demonstrate that TRPM2 has a novel role in facilitating breast cancer cell genomic integrity, survival, and proliferation. Because these effects are in direct contrast to the pro‐cell death role of TRPM2 in all other tissues and noncancerous cells studied, TRPM2 may represent a novel target in breast cancer treatment. More specifically, TRPM2 pharmacologic inhibition is expected to lead to the selective eradication of breast tumors. These results are therefore expected to provide a basis for inhibiting TRPM2 for the improved treatment of breast cancer patients.
A role for Gai‐GTP‐mediated inhibition of cAMP levels in neutrophil polarization and chemotaxis in response to chemoattractants (843.2)
Authors: Surve Chinmay , Kim Minsoo , Smrcka Alan
Published: June 2021

G protein βγ subunits released upon Gi activation are the major direct transducers of chemotactic GPCR‐dependent immune cell migration. We previously demonstrated that the small molecule 12155 binds to, and directly activates Gβγ signaling without activation of Gαi, and is sufficient to act as a chemoattractant in a solution‐based assay. To mimic adherence and migration on endothelial cells we examined mouse neutrophil migration on surfaces coated with ICAM‐1. Here, uniform application of fMLP resulted in cell polarization, and increased cell movement. In contrast, application of 12155 led to neutrophil adhesion and actin polymerization surrounding the cells without polarization, suggesting that signals other than Gβγ are required for cell polarization. Activation of Gi directly with Mas7 led to neutrophil polarization and migration indistinguishable from fMLP, suggesting that the missing signal is not from GPCRs but rather is Gαi activation. We compared cAMP levels in cells treated with fMLP and 12155 which increased cAMP levels by 2.5 and 4.7 fold respectively. This suggests that Gαi‐GTP moderates the increase in cAMP driven by Gβγ activation alone. Inhibiting PKA activity in the presence of 12155 led to cell polarization. These data support the hypothesis that Gαi‐GTP‐dependent suppression of cAMP levels is required for polarization of neutrophils in response to chemoattractants.
Peptide modulators of adenylyl cyclase signaling: modulation of receptor‐mediated Gβγ signaling (843.6)
Authors: Soto Velasquez Monica , Spence John , Brust Tarsis , Perez Minervo , Parker Laurie , Watts Val
Published: June 2021

The objective of this study was to explore the use of lipidated peptides as peptide modulators of adenylyl cyclase signaling (PMACS). The activity of several palmitoylated PMACS on adenylyl cyclase 2 (AC2) signaling was explored. AC2 is closely related to AC4 and AC7 and all of these isoforms are characterized by their ability to be conditional activated by Gβγ subunits. There are several putative Gβγ binding sites that are conserved between AC2, AC4, and AC7. The domains targeted here included the N‐terminus, a recently identified Gβγ binding region in C1a, and an uncharacterized domain in C2a. Initial studies examined the effect of each peptide on Gβγ potentiation of phorbol ester‐stimulated AC2 activity in intact cells. The peptides targeting the N‐terminus and C1a domain were inactive, however, the C2a domain peptide inhibited completely Gβγ potentiation of AC2 following activation of the D2 dopamine receptor. Additional experiments demonstrated that palmitoylation was required for activity, and that eliminating C terminal amino acids of the C2a‐targeted peptide reduced its potency. The C2a peptide also blocked Gβγ potentiation of Gαs‐stimulated cAMP accumulation of AC2, and Gβγ signaling involving μ opioid receptors. Further studies revealed that the C2a peptide attenuated Gi/o‐coupled receptor‐induced heterologous sensitization of AC2 and potentiated forskolin‐stimulated cAMP accumulation in HEK cells. These findings demonstrate that lipidated peptides can be applied to study receptor‐mediated Gβγ signaling as well as the regulatory properties of adenylyl cyclases.

Grant Funding Source: Supported by NIH Research MH60397 and Purdue University Research Incentive Grant