bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA‐like prototypic INH‐ODNs selectively inhibit B cell receptor for antigen (BCR) triggered TLR9 activation in autoimmune B cells
Authors: Lenert Petar , Ratnabalasuriar Radhika S. , Fleenor Courtney J. , Ashman Robert F. , Marshak‐Rothstein Ann
Published: June 2021

Multiple lines of evidence suggest a role for nucleic‐acid sensing receptors in the pathogenesis of SLE. Strategies to preferentially block autoimmune B cells may be preferred over currently advocated non‐selective B cell depletion protocols. We have developed a new generation of small TLR9 inhibitors (Class R INH‐ODNs). These DNA‐like INH‐ODNs have a very low potency for naive resting B cells, but are very potent inhibitors of macrophages and DCs. We wondered what the effects of these agents were on autoimmune B cells. Therefore, we studied the innate activation of autoreactive B cells from MRL‐lpr/lpr lupus mice and AM‐14 RF‐specific transgenic B cells. B cells were stimulated with linear or palindromic CpG ligands; or with immune complexes containing PL2.3 or ID4 antibodies. Both dsDNA‐reactive B cells and AM‐14 B cells were inhibited with low nanomolar concentrations of Class R INH‐ODN when activation required ligand delivery via the BCR. However, when autoreactive B cells were stimulated with linear TLR9 ligands, bypassing the BCR‐mediated entry, similarly to naïve resting B cells the potency of Class R INH‐ODNs was 10–33 fold lower. Similar differences were observed in MRL‐lpr/lpr mice in vivo where the prototypic Class R INH‐ODN appeared to be more effective compared to its linear derivative. In conclusion, refinement of Class R INH‐ODN structure for human use may result in a new line of therapeutics for SLE.
Dendritic cells transduced with lentiviral vectors expressing vasoactive intestinal peptide (VIP) differentiate into tolerogenic‐like DC
Authors: Toscano Miguel Garcia , Ganea Doina
Published: June 2021

It is of increased interest to generate DC with efficient and stable genetic modifications, i.e. expressing a protein with therapeutic effects, to be used as therapeutic tools. Previous results from our laboratory indicated that the neuropeptide VIP has both preventive and therapeutic effects in models of autoimmune diseases such as rheumatoid arthritis and experimental autoimmune encephalomyelitis. We had previously shown that the therapeutic effects of VIP are mediated largely through effects on DC, specifically on the generation of tolerogenic DC. However, direct treatment of human subjects with VIP could lead to significant side effects due to its action on both the cardiovascular system and gastrointestinal tract. Therefore, we used lentiviral vectors carrying the cDNA of human VIP for the transduction of DC during their differentiation from bone marrow cells. Mouse bone marrow DC were efficiently transduced by lentiviral vectors carrying eGFP (up to 60% of cells with an MOI of 10). Use of the same vectors carrying h‐VIP led to a DC population expressing close to 350 pg/ml of VIP. The VIP expressed by transduced DC acted in an autocrine manner; leading to the differentiation of tolerogenic‐like DC, characterized by a reduction in the costimulatory molecules CD40 and CD86 following LPS stimulation. In addition, we observed a downregulation in the production in the pro‐inflammatory cytokines IL‐6 and TNF‐a and an increase in IL‐10 (anti‐inflammatory cytokine).

This work was supported by NIH/NIAID R01AI052306
Natural human IgE peptide‐specific CTL inhibit human IgE production and eliminate U266 in HLA‐A2 transgenic rodents
Authors: Chen Swey‐Shen , Hatlen Megan , Barankiewicz Teresa
Published: June 2021

Cytotoxic T‐lymphocytes elicited against a human IgE peptide nonamer restricted to HLA‐A2.1, pWV inhibit human IgE production and lyse human IgE‐secreting U266. A high throughput cell‐based ELISA is correlated with FACS determination of upregulated MHC I in RMA‐S‐A2Kb cell line. The efficiency of lysis of U266 is optimized with A2Kb transgene that also facilitates interaction of murine α3 domain with murine CD8. Activated CTL also inhibit IgE production by A2Kb‐U266 and prevent its progression in A2Kb mice, tolerized with A2Kb‐U266. Validity of human IgE peptide immunization in targeting IgE‐secreting plasma cells is extended to murine IgE peptide in non‐transgenic normal BALB/c mice. CTL responses elicited by nonameric PI‐1 peptide in CpG are intermittent in protecting a concomitant allergen‐specific KLH response without eliminating the potential of IgE production. Following each successive round of vaccination, IgE responses are fully recovered in vivo; moreover, even during effective in situ IgE suppression, competent, undiminished antigen‐specific IgE production can still be elicited in vitro, indicating the potential. Taken together, the observation suggests that a relevant human natural IgE peptide may be employed as a CTL‐based vaccine for pan‐IgE human therapy against IgE‐mediated diseases.
Positive and negative regulation of FcεRI signaling by SHP‐1
Authors: Mizuno Kazuya , Nakata Kazuko , Nakata Hiroyasu , Yakura Hidetaka
Published: June 2021

SHP‐1 is a cytoplasmic tyrosine phosphatase and, in mast cells, has been shown to negatively regulate the initial signaling triggered by high affinity receptors for IgE (FcεRI). To clarify the molecular mechanisms of SHP‐1 in mast cells, we generated bone marrow‐derived mast cells (BMMCs) from SHP‐1‐deficient motheaten (me) and control (wt) mice and examined downstream signaling events and final outputs following FcεRI crosslinking. FcεRI‐induced tyrosine phosphorylation of SLP‐76 and LAT was increased in me‐derived BMMCs. The activity of Syk that is responsible for the phosphorylation of SLP‐76 and LAT was comparable in both BMMCs, implying that SLP‐76 and LAT might be substrates of SHP‐1 in mast cells. Lack of SHP‐1 expression resulted in enhanced activation of mitogen activated protein kinases, Erk, JNK, and p38, and transcription of cytokine genes such as TNFα and IL‐6, in good accordance with the previous implication of SHP‐1 as a negative regulator. In contrast, FcεRI‐induced calcium mobilization was severely impaired in me‐derived BMMCs. Whereas wt‐BMMCs showed sprolonged increase in calcium flux upon high intensity stimulation, BMMCs derived from me mice demonstrated decreased and transient responses. In addition, me‐BMMCs exhibited diminished calcium flux at low intensity stimulation. Thapsigargin induced similar level of calcium flux in both BMMCs, indicating that BMMCs lacking SHP‐1 expression are still capable of mobilizing calcium. These studies revealed that SHP‐1 not only regulates FcεRI‐signaling negatively but can act as a positive regulator in mast cells. The experiments to clarify possible molecular mechanisms for the positive regulation of calcium signaling by SHP‐1 are currently under study.
Identification of the immediate precursors of tumor dendritic cells
Authors: Diao Jun , Winter Erin , Cattral Mark S.
Published: June 2021

The ontogeny of dendritic cells (DC) in tumors remains unclear. Our previous studies have shown that conventional DC (cDC) in murine lymphoid tissue and bone marrow arise from a distinct population of CD11c(+) MHC class II(−)lineage(−) immediate precursors, which are now known as pre‐cDC. In this study, we show that pre‐cDC are a key source of DC in experimental murine tumors. Pre‐cDC from tumors are replication‐competent and generate homogeneous cDC that continue to divide for several generations when co‐cultured on a supportive stromal monolayer. Adoptively transferred pre‐cDC, but not monocytes, generate DC in tumors. In vivo bromodeoxyuridine incorporation studies reveal that endogenous pre‐cDC and cDC are actively replicating in tumors. The chemokine, CCL3, was found to play a critical role in promoting pre‐cDC migration into tumors from the circulation. Collectively, our findings provide evidence of a distinct development pathway for cDC in tumors and highlight the importance of in situ replication of pre‐cDC and cDC in their expansion. The identification of this pathway is an important step in addressing how tumor microenvironments influence the developmental fate and function of DC.
IL12 polarization of mouse and human T‐cells: implications for adoptive immunotherapy
Authors: Johnson Laura Alexandra , Kaiser Andrew , Paulos Chrystal M , Powell Daniel J , Heemskerk Bianca , Restifo Nicholas P , Rosenberg Steven A
Published: June 2021

Adoptive immunotherapy with TCR transduced autologous PBL can mediate objective clinical responses in patients with advanced metastatic melanoma. Different factors affecting adoptively transferred cells include avidity and affinity of the TCR, TCR expression, differentiation state, and immunological phenotype of the transferred cells. In vitro, naïve murine splenocytes can be polarized into Type 1, 2 or 3 (Treg) cells by TCR activation in the presence of specific cytokines. Here we show both TCR‐specific murine and human T‐cells can be polarized into a Type 1 phenotype by TCR stimulation in presence of IL12, using whole PBL or naïve T‐cells. In both models, IL12 polarized T‐cells produced the most IFNg in response to tumor antigen stimulation, and had the highest lytic capabilities against cognate antigen‐bearing tumor targets in vitro. Unexpectedly, IL12 programmed human T‐cells demonstrated a reduction in FoxP3+CD4+ cells, suggesting reduced Tregs, while maintaining similar expansion. We found that IL12 polarization of TCR‐specific T‐cells from both mouse and human donors resulted in similar in vitro anti‐tumor phenotypes. These results, combined with our finding that IL12 polarized cells demonstrated superior tumor regression on established tumors in an animal model, suggest the potential to utilize IL12 polarization of TCR transduced human PBL in the clinic to treat patients with cancer.
Melanoma cells expressing membrane‐anchored IL‐2 and IL‐12 induce effective antitumor immunity in the presence or absence of B7‐1 costimulation
Authors: Shashidharamurthy Rangaiah , Panchanathan Ravichandran , Fiske Erik D , Tien Linda , Selvaraj Periasamy
Published: June 2021

Systemic and local administration of cytokines has been used as a strategy to induce an antitumor immune response to enhance the antitumor effects of many cancer vaccines. This study investigates the antitumor effects of certain cytokines and costimulatory molecules expressed on tumor cell surface as a glycolipid (GPI)‐anchored form using a murine melanoma (S91 clone M3) model. Stable transfectants of S91 cells expressing immunostimulatory molecules, such as B7‐1, IL‐2, and IL‐12, alone and in combinations were established. The transfected cells induced the proliferation of activated T cells, indicating that membrane‐expressed GPI‐anchored cytokines can stimulate immune cells directly. To determine the in vivo efficacy of these immunostimulatory molecules, groups of mice were challenged with transfected cells and no tumor growth was observed. After 56 days of observation, the immunized mice were re‐challenged with wild‐type S91 melanoma cells. The mice immunized with transfected cells did not develop tumors whereas the unimmunized control mice developed tumors. In summary, our results show that the GPI‐anchored cytokines alone or in combination with B7‐1 can augment antitumor immune response, which suggest that the combination of immunostimulatory molecules expressed on melanoma cells can be used as a vaccine against melanoma.
Lentiviral overexpression of Peroxisome Proliferator‐activated receptor gamma (PPARγ) induces apoptosis in human multiple myeloma cells
Authors: Garcia‐Bates Tatiana Margarita , Bernstein Steven H. , Phipps Richard P.
Published: June 2021

Peroxisome proliferator‐activated receptor γ (PPAR‐γ) is a transcription factor that has key role in adipocyte differentiation. PPARγ also regulates immune and inflammatory responses. Our laboratory has demonstrated that normal and malignant B cells express PPARγ and that exposure to certain PPARγ ligands inhibits their proliferation and induces apoptosis. These studies support a key role for PPARγ in B lymphocyte activation and death. We first examined the functional consequences of PPARγ overexpression in human multiple myeloma cells using a lentiviral vector approach. Human multiple myeloma 8226 cells were infected with a lentivirus expressing PPARγ. Here, PPARγ overexpression decreased multiple myeloma cell proliferation and induced spontaneous apoptosis, even in the absence of exogenous ligand, as determined by 3H thymidine and BrdU incorporation, annexin‐V‐7AAD staining, DAPI staining and caspase activation. The decrease in proliferation was associated with increased levels in p21 and decreased cyclin D1 levels. These cells were dramatically more sensitive to PPARγ‐ligand exposure, as treatment with ciglitazone enhanced apoptosis. Collectively, these findings support a regulatory role for PPARγ in the proliferation and apoptosis of malignant B cells and suggest the potential of PPARγ as a therapeutic target for multiple myeloma. Supported by DE011390 and the Leukemia and Lymphoma Society
IL‐12/IL‐23 production induced by Toll‐like receptor agonist primed myeloid dendritic cells is differentially regulated by prostaglandin E2
Authors: Xu Min , Xu Shuwen , Roses Robert E. , Koldovsky Ursula , Koski Gary K. , Czerniecki Brian J.
Published: June 2021

DCs are potent APCs. Besides providing signal one and two in T cell activation, DCs critically provide third signals that direct T cell polarization. Important third signaling molecules produced by DCs include IL‐12 and IL‐23. IL‐12, however, is anti‐angiogenic and enhances anti‐tumor immunity while IL‐23 is pro‐angiogenic and is linked with chronic inflammation associated tumorigenesis. We examined the role of PGE2, a ubiquitous inflammatory molecule, in regulating IL‐12 and IL‐23 production by myeloid DCs. TLR agonists comparably matured DCs whether used singly, in pairs, or in conjunction with IFN‐γ. Maximal IL‐12 production, however, required TLR agonist pairing or combinations of single TLR agonist with IFN‐γ. Adding PGE2 enhanced the migratory capacity of all DCs. PGE2 also significantly inhibited IL‐12 production while increasing the production of IL‐23. PGE2‐treated, TLR agonist‐activated DCs also demonstrated an enhanced ability to activate Th17 cells at the expense of Th1 in the allogenic MLR. Moreover, addition of PGE2 inhibited TLR agonist‐activated DC from sensitizing high avidity, tumor‐recognizing CTL. Because of the profound functional divergence of the IL‐12/Th1 and the IL‐23/Th17 axis as it relates to cancer resistance, the balance of IL‐12 and IL‐23 production by DC may play a critical role in regulating tumor promotion or regression and should be considered in tumor vaccine design.
A 3‐year longitudinal study of zinc status in infants fed human milk (HM), casein‐based (CBF), or soy‐based formula (SBF) in Korea
Authors: Hyun Taisun H , Han Young‐Hee , Yon Miyong , Han Heon‐Seok , Lee Yoon‐Bok , Tamura T
Published: June 2021

Zinc nutritional status was longitudinally assessed by measuring zinc intakes and serum zinc concentrations from birth to 36 months in 51 infants who were exclusively fed HM (n=20), CBF (n=12), or SBF (n=19) during the first 5 months of life. Zinc contents in milk and formulas were measured, and zinc intake was estimated at 1–36 months of life by weighing infants before and after feeding in the HM group and by collecting formula intake records in the CBF and SBF groups. After solid foods were introduced, all foods consumed were also included to estimate zinc intake. Mean daily zinc intakes were 1.0, 3.8, and 7.0 mg at 5 months and 3.8, 5.8 and 11.6 mg at 12 months and 5.5, 3.7, and 6.0 mg at 36 months in the HM, CBF, and SBF groups, respectively. Although the overall zinc intake in infants fed SBF was higher than those in the HM or CBF groups throughout the study, mean serum zinc concentrations were similar in all groups. The proportions of infants with low serum zinc (< 65 μg/100 mL) were 10%, 17%, and 20% at 5 months, and 42%, 30%, and 12% at 12 months, and 33%, 13%, and 20% at 36 months in the HM, CBF, and SBF groups, respectively, suggesting the presence of inadequate zinc status. The strategies to increase zinc intake in the HM group and to increase bioavailability of zinc in CBF or SBF should be studied. Research Support: Dr. Chung's Food Co.
The health and nutrition status of Vietnamese wives in Korea
Authors: Lee Sang‐Eun , Lyu Ji‐Eun , Chung Hye‐Won , Kim Wha‐Young
Published: June 2021

In recent years, international marriages have been rapidly increasing in Korea. The purpose of this study was to assess health and nutrition status for Vietnamese wives in Korea. The subjects were recruited from a medical examination center in Seoul. The mean age of the subjects was 24.7±0.3 years and mean length of residence in Korea was 2.8 years. The mean BMI (body mass index), systolic, diastolic blood pressure, HDL‐cholesterol, triglycerides and fasting blood glucose of the subjects were within the normal ranges. However, some subjects should abnormal anthropometry and hematological variables as follows high BMI; 7.4%, high blood pressure; 6.8%, low HDL‐cholesterol; 59.2%, high triglycerides; 12.8%, and high fasting blood glucose; 0.3%. Intakes of protein and vitamin C were above Estimated Average Requirements (EAR). However, intakes of vitamin A, iron, zinc and folate did not meet EAR. In conclusion, anthropometry and hematological variables were within the normal ranges. However, status of nutrient intakes was not satisfactory, especially intakes of antioxidant nutrients such as vitamin A and folate were lower than EAR. The society must give special attention so that the Vietnamese wives should be encouraged to lead a stable dietary life. (This study was supported by a grant of the Korea Centers for Disease Control and Prevention (2006‐347‐2910‐213‐207) and second stage of BK21 project in 2007.)
Gestational diabetes, nutrient intake, anthropometry and ethnicity: Associations to risk factors for type 2 diabetes in young women
Authors: Young Tara , Peerson Janet , Steinberg Francene
Published: June 2021

There is a lack of research investigating the correlation between metabolic risk factors for Diabetes Mellitus (DM) and a history of gestational diabetes (hGDM). The objective of this analysis was to determine the correlation between hGDM, diet, body mass index (BMI), ethnicity and biochemical markers associated with DM. Data from the National Health and Nutrition Examination Survey III was analyzed using SAS Survey Regression procedures. Subjects included women who were < 5 years post‐partum without type 2 diabetes. Dependent variables included insulin, glucose, glycosylated hemoglobin (HbA1c), c‐peptide and HOMA. Independent variables included hGDM, BMI, ethnicity, nutrients and other covariates, including caloric intake, age, education, and income. Nutrients including total fat, saturated fat, total fiber, insoluble fiber, magnesium (Mg) and zinc were analyzed in separate models. BMI was positively associated with all dependent variables. hGDM was positively associated with all variables except HbA1c. Mg was inversely associated with all variables except HbA1c. Total fat was inversely associated with HbA1c. There were no significant effects for ethnicity or other nutrients. These results underscore the significant impact of hGDM and Mg, independent of BMI and other covariates, on biomarkers associated with DM risk. Support: Pfeiffer Foundation.
Micronutrient quality of weight loss diets that focus on macronutrients: results from the A TO Z study
Authors: Gardner Christopher D , Kim Soowon , Morris Jennifer L , Bersamin Andrea , Cherin Rise
Published: June 2021

Information on diet quality of alternative weight loss diets is limited. Our objective was to compare nutrient intake among overweight/obese women randomly assigned to the Atkins (n=73), Zone (n=73), LEARN (n=72), or Ornish (n=73) diets. Diet data were collected by 3‐day, unannounced, 24‐hour recall at baseline and after 8 weeks of diet instruction. Nutrient intakes were compared between groups at 8 weeks, and within groups for changes in risk of micronutrient deficiency (<2/3 RDA) between baseline and 8 weeks. At 8 weeks there were significant differences among groups for all macronutrients and many micronutrients (p<0.0001). Energy intake decreased from baseline for all 4 groups but was similar among groups. The proportion of individuals at risk of deficiency increased significantly (p<0.05) in the Atkins group for thiamin, folate, vitamin C, iron, and magnesium; in the LEARN group for vitamin E and calcium; and in the Ornish group for vitamins E and B12 and zinc. In contrast, for the Zone group the risk of deficiencies significantly decreased for vitamins A, C, E and K (p<0.05) with no significant increases in risk of deficiency. Weight loss diets that emphasize macronutrient composition should consider not only the weight loss outcomes, but also the adequacy of micronutrient intakes. This research was supported by NIH and the Community Foundation of Southeastern Michigan.
Energy expenditure and physical activity in recovering malnourished infants
Authors: Rising Russell
Published: June 2021

Background: Malnourished infants are small for age and weight.

Objectives: Determine 24‐hour energy expenditure (24‐h EE) and physical activity (PA) in recovering malnourished infants.

Methods: 10 malnourished infants (58.1 ± 5.9 cm, 7.7 ± 5.0 months), six classified as primary and four as primary/secondary, were determined to be healthy prior to spending 24‐hours in the Enhanced Metabolic Testing Activity Chamber for measurement of EE, resting (RMR) and sleeping metabolic rates (SMR), respiratory quotient (RQ; VCO2/VO2) and PA (oscillations in wt/min/kg BW). Energy intake and percent sleep were recorded. These data were compared to similar results from 10 healthy infant controls (68.8 ± 2.8 cm, 5.0 ± 0.8 months). Data analysis (SPSS, Version 13) involved independent t‐test (p<0.05) between malnourished and healthy controls and expressed as kcal/kg/day.

Results: In comparison to controls, malnourished infants were lighter (4.1 ± 1.2 vs. 7.3 ± 0.8 kg; p<0.05) and had a lower BMI (12.0 ± 1.7 vs. 15.5 ± 1.5; p<0.05). In contrast, malnourished infants had greater energy intake (142.7 ± 14.6 vs. 85.1 ± 25.8; p<0.05) with a greater percentage of carbohydrates (55.1 ± 3.9 vs. 47.2 ± 5.2; p<0.05). However, malnourished infants had greater 24‐h EE (101.3 ± 20.1 vs. 78.6 ± 8.4; p<0.05), RMR (90.9 ± 18.4 vs. 66.0 ± 3.5; p<0.05), SMR (92.6 ± 17.1 vs. 65.0 ± 3.9; p<0.05) and RQ (1.00 ± 0.13 vs. 0.86 ± 0.08; p<0.05). Moreover, malnourished infants also slept more (57.2 ± 6.8 vs. 49.7 ± 6.0 %; p<0.05) and had a lower amount of PA (2.3 ± 0.94 vs. 4.0 ± 1.5; p<0.05) in comparison to controls. Moreover, malnourished infants lacked a metabolic circadian rhythm.

Conclusion: Malnourished infants require more energy, possibly for growth. Moreover, it appears they conserve energy by a reduction in PA, greater amount of sleep and the elimination of the metabolic circadian rhythm.
Accuracy of Self Reported Weight Status in a College Population
Authors: Buechler Angela , Malinauskas Brenda , Heidal Kimberly , Duffrin Melani
Published: June 2021

The American College Health Association estimates that 31% of college students are overweight or obese. It is important that students have a correct perception of body weight status as extra weight has adverse health effects. This study assessed accuracy of perceived weight status versus medical classification among 102 college students. Perceived weight status was determined by responses to these questions, as part of a health questionnaire, “Are you overweight?” and “Which of the following best describes you?” (obese, overweight, normal weight, under weight). Medical classification was indicated from body mass index (using researcher‐recorded weight and height) based on World Health Organization standards. Seventy eight percent of participants (n = 80) correctly assessed their weight status with significantly more females (79%, n = 45 of 57) than males (53%, n = 24 of 45) correctly assessing their status (p < 0.01). All participants who misclassified their weight (n = 33) under classified their status as compared to the medical classification. Participants who correctly classified their status were, on average, 0–10 pounds overweight whereas those who misclassified were 11–20 pounds overweight. Among college students, nutrition education strategies should focus on students correctly identifying their weight status and health implications associated with an overweight/obese condition.
Development of a Body Fat Prediction Equation for Young Adults
Authors: Zanovec Michael , Tuuri Georgianna
Published: June 2021

Given the rising prevalence of obesity, particularly in young adults, it is important to develop valid field‐based methods that can used to estimate body fatness. Body mass index (BMI; in kg/m2) is currently used to categorize obesity, despite the fact that BMI is only moderately correlated with percent body fat. The purpose of this study was to develop a body fat prediction equation specifically for a college‐aged population. 270 Caucasian (n=161) and African American (n=109) students aged 18‐24 volunteered to participate. Height and weight were measured and BMI values calculated. Total percent body fat (%BF) was estimated using dual‐energy X‐ray absorptiometry (DXA). Stepwise multiple linear regression examined significant predictor variables of %BF, including gender, race, age, and BMI. The predicted residual error sum of squares (PRESS) statistic cross‐validated the model. The reduced model explained 80% of the variance in total percent body fat (%BF = 1.53[BMI] ‐ 16.47[gender] ‐ 1.29[race] ‐ 4.5; note: 0 =female, 1=male; 0=Caucasian, 1=African American). Additionally, the root mean squared error (RMSE) for the model (4.2 %BF) was equivalent to the cross‐validation statistic. These results suggest that body adiposity can be predicted with greater accuracy in a college‐aged population when gender and race are included in addition to BMI.

Grant Funding Source: N/A
Modulation of heart rate variability by dietary carbohydrate in healthy adolescent African‐Americans
Authors: Austin Rachel E. , Bond Vernon , Polk Octavius D. , Millis Richard M.
Published: June 2021

Low heart rate variability (HRV) after eating may be a risk factor for obesity among African‐Americans because of its association with a limitation of postprandial sympathetic regulation of adipokinesis and fat utilization.

Purpose

The present study was designed to test the hypothesis that a subpopulation of adolescents may be differentiated by changes in HRV after ingesting beverages of high carbohydrate or high fat content.

Methods

HRV was computed as the standard deviation of the normal‐normal (SDNN) and as the very low, low and high frequency spectral powers measured on electrocardiogram (ECG) RR intervals during paced breathing. Respiratory exchange ratio (RQ) and metabolic energy expenditure were measured.

Results

The results showed that RQ consistently increased after ingestion of the high carbohydrate and did not change consistently after ingestion of the high fat beverages. The peak increment in RQ was associated with an increase in the very low frequency and a decrement in the high frequency in the absence of consistent changes in the low frequency ECG spectral power.

Conclusion

These findings suggest that ingestion of high‐carbohydrate may produce sympathetic modulation of metabolism and thermogenesis in healthy adolescent African‐Americans. Furthermore, carbohydrate induced production of carbon dioxide may function as a metabolic signal for autonomic nervous system activity and HRV. The results of this study suggest that the increment in very low frequency ECG spectral power associated with ingestion of carbohydrate may be a physiological marker for postprandial sympathetic mediated adipokinesis, a limitation of which could be a marker of increased risk for obesity.
RNA Catalysis: Ribozymes, Ribosomes and Riboswitches
Authors: Strobel Scott
Published: June 2021

The catalytic mechanisms employed by RNA are chemically more diverse than initially suspected. Divalent metal ions, nucleobases, ribosyl hydroxyl groups, and even functional groups on metabolic cofactors all contribute in the various strategies employed by RNA enzymes. This catalytic breadth raises intriguing evolutionary questions about how RNA lost its biological role in some cases, but not in others, and what catalytic roles RNA might still be playing in biology.
The influence of expeller processed soybean oil on lipid responses in rats
Authors: Shadzi Pey , Alvarez Elizabeth , Price Penny , Ciepiela Magdalena , Kern Mark
Published: June 2021

Oil refinement has been demonstrated to reduce the content of potentially important nutritional components of food oils such as polyphenols. The influence of soybean oil refinement on health‐related properties has not been an active area of investigation. This study was designed to assess the influence of expeller pressed soybean oil (EPSO) versus conventionally refined soybean oil (RSO). Sixteen male weanling Sprague‐Dawley rats were equally divided into two groups. Rats consumed diets consisting of 20% fat by weight from either EPSO or RSO for 30 days. At the end of the study, animals fed EPSO tended to have a lower (p=0.065) body weight with no difference (p>0.05) in epididymal fat weight. EPSO‐fed rats exhibited significantly lower (p<0.05) serum concentrations of triglycerides and non‐HDL‐cholesterol with higher (p<0.05) HDL‐cholesterol. No differences in serum glucose, insulin, or leptin were detected. Results suggest that consuming a diet containing a minimally processed soybean oil promotes an improved blood lipid profile in rats relative to consuming a refined soybean oil. Research is needed to determine the safety of unrefined soybean oil for animals and humans and to determine if similar positive effects occur in humans.
Relationship between nutritional biomarkers and health status in the Korean elderly women
Authors: Yang Eunju , Chung Haekyung
Published: June 2021

This study was performed to exam association between nutritional biomarkers and health status based on metabolic syndrome (MS) and obesity in the elderly women. This was a across‐sectional study involving Korean elderly women (≥60, n=99) and socio‐demographics, life style characteristics, health conditions, dietary behavior, anthropometric measures (wt, ht, waist, hip, body protein, body fat, and abdominal fat, triceps skinfold thickness), and nutritional biomarkers (serum total cholesterol, HDL‐cholesterol, triglyceride, total protein, albumin, prealbumin, hemoglobin, hematocrit, fasting blood glucose, HbA1C, ferritin, Zn, Ca, Na, K, Vt. B12, folate), and systolic blood pressure and diastolic blood pressure were examined. MS group had significantly higher WBC, serum TG and glucose level, but had lower serum HDL‐cholesterol and folate level than normal elderly women. Obesity group had significantly higher serum TG and glucose level, but lower serum HDL‐cholesterol level than normal weight elderly women. Serum TG, HDL‐cholesterol, and glucose were significantly correlated with BMI, waist, WHR, and abdominal fat(%) which suggested the risk of abdominal obesity for health status in the Korean elderly women. Other nutritional biomarkers except serum folate were not significantly related to the health status in the elderly women. These results suggest that serum TG, HDL‐cholesterol, glucose, and abdominal obesity may be the important risk factors in the Korean elderly women. (Funded by the Korea Research Foundation)
Vitamin B6 intake/supplementation, Plasma PLP and inflammatory disease
Authors: Barrett Lydia , Selhub Jacob , Troen Aron , Bujanover Yoram
Published: June 2021

Introduction: Patients with the inflammatory disease, rheumatoid arthritis, have significantly lower plasma pyridoxal‐5‐phosphate (PLP) levels than controls, despite normal intakes and metabolism of vitamin B6. Because of the theoretical role for PLP in the inflammatory response, we sought to investigate plasma PLP levels in patients with other chronic inflammatory conditions. Methods: We searched pubmed for studies that examined plasma PLP levels in diseases that are known to involve inflammation, using keywords such as plasma PLP, vitamin B6, inflammation, rheumatoid arthritis, inflammatory bowel disease, diabetes, obesity, and cardiovascular disease. Results: All studies that examined plasma PLP levels in patients with rheumatoid arthritis (N=5), inflammatory bowel disease (N=1), and diabetes (N=3) reported that patients had lower levels of plasma PLP than controls despite normal intakes. For CVD, 16 out of 20 studies found patients to have lower plasma PLP levels than controls and/or a higher prevalence of PLP deficiency than in controls. Collectively, these studies find plasma PLP to be inversely correlated with markers of inflammation including: CRP, α‐acid‐glycoprotein, fibrinogen, ICAM, VCAM, IL‐6r, and erythrocyte sedimentation rate. Discussion: The basis for these relationships is presently unclear. Supplementation with B6 is effective in increasing plasma PLP levels, but this does not seem to bring about an improvement in disease outcomes. A possible explanation for this phenomenon is that the observed decrease in plasma PLP is caused by its mobilization and utilization by the inflamed tissue. If so, in those cases where chronic inflammation has adverse effects, PLP supplementation could be harmful. Clearly, further research into the role of PLP in inflammatory disease is a priority.
Potential impact of policy changes to eliminate the availabilty of sweetened beverages in elementary schools: evidence from the Early Childhood Longitudinal Study
Authors: Gonzalez Wendy , Jones Sonya J , Frongillo Edward A
Published: June 2021

Sweetened beverage consumption has been associated with negative nutritional and health consequences for children. Schools, school districts, and states have developed policies to regulate availability of sweetened beverages under the largely untested assumption that such regulation will affect purchase and consumption. We tested whether availability of these beverages in school was associated with children's purchase at school and total daily consumption. The US nationally representative Early Childhood Longitudinal Study—Kindergarten cohort 5th grade panel data were used. Multi‐level regression models that accounted for clustering of children in schools examined the relationships of availability, purchase, and consumption behaviors. Sweetened beverages were available in 26% of elementary schools. Children were five times more likely to purchase a sweetened beverage at least once per week if available in school. Availability of alternatives, particularly bottled water, lessened somewhat the probability of purchase of sweetened beverage. In schools where sweetened beverages were available, purchase of these beverages was related to frequent or occasional consumption. Our findings provide evidence that having sweetened beverages available is related to their consumption, suggesting that policy changes to eliminate availability of sweetened beverages could potentially have an impact.
Inhibition of chlorophyll derivatives on aflatoxin B1‐induced damage in hepatoma cells
Authors: HSU CHING‐YUN , HU SHENE‐PIN , CHEN CHIAO‐MING
Published: June 2021

The inhibitory effects of four chlorophyll derivatives (chlorophyllide a and b [Chlide a and b] and pheophorbide a and b [Pho a and b]) on aflatoxin B1 (AFB1)‐DNA adduct formation, and on the modulation of hepatic glutathione S‐transferase [GST] in murine hepatoma (Hepa‐1) cells were evaluated. Enzyme‐linked immunosorbent assay was used for the former and spectrophotometric assay for the latter. Pretreatment with Chlide or Pho (20 and 50 μM) significantly reduced the formation of AFB1‐ DNA adducts, and Pho was the more potent inhibitor. However, wash out prior to adding AFB1 totally eliminated inhibition by Childe and partially eliminated inhibition by Pho, indicating the inhibitory effect of Chlide, and to some extent Pho, was mediated through direct trapping of AFB1. Furthermore, Pho or Chllin treatment can also increase GST activity in Hepa‐1 cell. These observations indicate that all the chlorophyll derivatives may attenuate AFB1‐induced DNA damage in the Hepa‐1 cell by direct trapping of AFB1. Pho had more protective effect not only by direct trapping but also modulating GST activity to hepatic AFB1 metabolites.
The effect of consuming pistachios on the high‐density lipoprotein (HDL) concentration of lutein and zeaxanthin (L/Z)
Authors: Radcliffe John , DiMarco Nancy , Imrhan Victorine , Grubesic Ruth , Hernandez Ladia
Published: June 2021

HDLs play a key role in the transport of L/Z into the retina. Retinal L/Z, which reflects serum L/Z concentration, may protect against age‐related macular degeneration (AMD). Pistachios are a dietary source of L/Z, and consumption of these nuts may beneficially affect L/Z status. The effect of consumption of pistachios (68 g per day) on HDL‐L/Z was investigated in a 6‐wk feeding study with healthy adult volunteers (17 female, 13 male; mean age 38 yr) randomized into a control (n = 14) and an intervention group (n = 16). Both groups consumed their usual diets for the first two weeks of the study; for the next 4 weeks, the control group consumed their usual diets, and the intervention group was given pistachios to incorporate into their diets. HDL‐L/Z decreased by 4% for the control group but increased 52% for the intervention group; similar changes were noted for the TC‐L/Z (−1% for the control group and +53% for the intervention group). Thus, consumption of pistachios may be useful in protecting against AMD, the leading cause of blindness in adults over 65 years of age in the U.S.

Funding: TWU Human Nutrition Fund; Texas Dept. of Agriculture
Cooking process decreased nutaceutical contents and anticancer effects of Angelica keiskei in human cancer cells
Authors: Park Kun‐Young , Kim Boh‐Kyung , Bak Soon‐Sun , Kim Tae‐Seok , Yeo Ik‐Hyun
Published: June 2021

Changes of nutraceuticals and anticancer effects of Angelica keiskei with cooking process were evaluated. Cooked Angelica keiskei was prepared with heat in boiling water at 100°C for 5min, 10min and 20 min, respectively. The contents of carotenoids and chlorophyll of raw Angelica keiskei were higher than those in cooked Angelica keiskei and the contents significantly decreased by the cooking treatment in a time‐dependent manner. The juice of Angelica keiskei inhibited the survival of AGS human gastric adenocarcinoma cells and HT‐29 human colon carcinoma cells in MTT assay and growth inhibition test. The juice of raw Angelica keiskei exhibited stronger antiproliferative effect than that of cooked Angelica keiskei against the cancer cells. The juice of raw Angelica keiskei showed a higher inhibitory effect (83%) on the growth of AGS human adenocarcinoma cells than that of the 20 min cooked Angelica keiskei (47%) at 40 μl/mL. The raw Angelica keiskei induced apoptosis in the AGS cells by DAPI staining. The raw Angelica keiskei induced apoptosis in the AGS cells was associated with the decreased mRNA and protein expressions of the anti‐apoptotic Bcl‐2 and increased the expressions of Bax. The content of lutein of raw Angelica keiskei was higher than that in cooked. Lutein also induced apoptosis in the AGS cells associated mRNA and protein expressions of Bcl‐2 and Bax.
Hypoglycemic Effect of Korean Red Ginseng according to the Processing Methods in Streptozotocin‐Induced Diabetic Rats
Authors: Chung Young‐Jin , Kim Shin‐Hee
Published: June 2021

Hypoglycemic effects of Korean red ginseng according to processing methods was investigated in STZ‐induced diabetic rats. Five weeks‐old SD rats were divided into 5 groups; normal control (NC) group, STZ‐induced diabetic (DM) group, red ginseng (RG) group, fermented red ginseng (FG)group and pupped red ginseng (PG) group. RG, PG and FG groups fed the corresponding ginseng powder (500mg/kg) for 7 weeks after single injection of STZ (50mg/kg, i.v.). Body weight gain looked to be more in three ginseng groups compared to DM group. At week 7, the FBS levels of the RG, FG and PG groups were reduced by 12.88%, 11.7% and 21.55% when compared with DM group. The AUC levels in OGTT was not significantly different among the groups Serum insulin and TG levels were most significantly improved in PG group and serum amylase level was increased in RG group(p<0.05). DNA damage of blood lymphocyte deceased in PG group. Histopathological results of pancreas showed that destruction of exocrine as well as endocrine might be prevented by red ginseng administration. Immunohistochemistry of glut2 were improved in the three ginseng treated groups. From this result, it was suggested that pupped ginseng could be a depressant of STZ‐induced toxicity.
Experimental animal model to study of diet supplementation with phosphorylated alpha glucomannan polysaccharide
Authors: Lindemann Garrett W , Guerrero Antonio , Alonso‐Lebrero Jose L , Valdes‐Hevia Marta D , Brieva Aurora , Reyes Eduardo , Griffin Cristina E
Published: June 2021

The WHO has recommended that antibiotics not be used for growth promotion in feed animals. The purpose of this study was to compare the efficacy of Candida utilis alpha phosphoglucomannan (GLPH‐1) to a commercially available bacitracin (BMD60) in broiler chickens. A three hundred forty five poultry study was conducted with Ross x Ross male broiler chickens to evaluate the efficacy of GLPH‐1 to a commercially available BMD60 at a sub‐therapeutic level in a production setting. On study days 7, 14 and weekly there after food intake per pen and individual body weights were collected for the determination of body weight gain. We found that GLPH‐1, feed at 1 mg per kg body weight, as a growth promoting additive increased body weight and gain by 2.87% and 3.10% respectively. The use of GLPH‐1 is not associated with increased mortality. In the group treated with diet including BMD60, as a growth promoting additive, suffered a reduced accumulated survival at 15, 21 and 49 days of treatment of 84.34%, 80.00% and 78.26% respectively as well as suffered a diminished percentage of body weight and weight gain with respect to the group treated with a diet not containing any growth promoting additive (−3.72% and −4.03% respectively). The main finding of this study was that a substantial improvement in chicken mortality and body weight gain in the presence of GLPH‐1. GLPH‐1 is also a good growth promoting additive, safe and efficacious.
Tissue Expression of Fasting‐Induced Adipocyte Factor in Cattle
Authors: Mamedova Liaman , Bradford Barry , Robbins Kabel , Johson Brad
Published: June 2021

Fasting‐induced adipocyte factor (FIAF; also known as angiopoietin‐like 4) is a plasma protein that stimulates the oxidation of fatty acids and inhibits fat accumulation. The gastrointestinal tract appears to play an important role in regulating plasma FIAF concentration in some situations. Bovine FIAF shares 87% homology with the mouse protein. Our aim was to determine tissue expression of FAIF in the bovine. Rumen, omasum, abomasum, duodenum, jejunum, ileum, colon, pancreas, liver and adipose tissue samples were collected postmortem from 2 steers. FIAF mRNA was quantified by qPCR, and was most abundant in liver (420 arbitrary units; AU) and adipose tissue (320 AU). We detected FIAF mRNA throughout the gastrointestinal tract, with values ranging from 10 AU in the abomasum to 28 AU in the abomasum. By Western blot, FIAF protein was most abundant in liver and adipose tissue. However, FIAF protein was barely detectable in the rumen or duodenum, but was highly abundant in the omasum. Finally, cross‐sections of the rumen wall were used for immunohistochemistry staining, and strong signals for FIAF were detected in the epithelial layer. These findings suggest host/microbe interactions may influence FIAF expression in the ruminant gastrointestinal tract.
Dietary supplementation with cholesterol (Chol) and docosahexaenoic acid (DHA) alters the profiles of amino acids in tissues of neonatal pigs
Authors: Li Peng , Kim Sung Woo , Datta Sujay , Pond Wilson G. , Wu Guoyao
Published: June 2021

Enogenous synthesis of Chol is limited in neonates. However, its concentrations in current infant formulae remain low. DHA is a component of complex lipids in membranes and a precursor for signaling molecules. Sixteen newborn pigs were nursed by sows for 24 h and then assigned to one of 4 treatment groups, representing supplementation with 0.0%, 0.2% Chol, 0.2% DHA, and Chol plus DHA to the basal formula consisting of coconut oil, soybean oil, soybean flour, whey, whey protein concentrate, minerals and vitamins. All piglets were euthanized at day 49 of life. Plasma, brain, liver and gastrocnemius muscle were analyzed for amino acids using HPLC methods. Chol supplementation increased (P<0.05) concentrations of Val, Ile and Leu in plasma, Gly, Arg, Lys and GABA in brain, and Gly in muscle, while reducing (P<0.05) concentrations of Glu, Gln and Thr in brain and Arg in liver. DHA supplementation increased (P<0.05) concentrations of Ser, Thr, Arg, Met, Val, Ile, Leu and Lys in plasma, Arg in brain, Asn in liver, and Asp, Glu, Asn, Ser, Gln, Ala, Leu and Lys in muscle, while reducing concentrations of Gln in brain and carnosine in muscle. There were interactions between Chol and DHA in their effects on branched‐chain amino acids in brain. The tissue‐specific effects of Chol and DHA on neurotransmitter and regulatory amino acids may play an important role in neonatal growth and development. Supported by TAES and NCSU.
Choice of diet impacts the incidence of stroke in the spontaneously hypertensive stroke‐prone rat model
Authors: Scanlan Adam P , Shaughnessy Kevin S , Sweeney Marva I , Gottschall‐Pass Kathy T
Published: June 2021

Selecting appropriate research models is of utmost importance as incorrect models can lead to misleading results. The spontaneously hypertensive stroke‐prone rat (SHRSP) is a commonly used model of cerebrovascular disease and hypertension. Signs of stroke are reported to be observed in SHRSP typically by age 14 weeks, involving any or all of the following acute symptoms: loss of coordination, twitching, weight loss, loss of appetite, and lack of thriftiness. However, after feeding a standard AIN93G purified diet, and 1 or 2% NaCl in water for 8 or 17 weeks, none of the symptoms of stroke were observed in any SHRSP in our laboratory (n=15). Thus, a follow‐up pilot study compared the incidence of stroke in SHRSP fed AIN93‐G purified diet to a commercially available rat chow starting at age 8 weeks. All rats had 4% NaCl in the diet. All SHRSP fed chow showed stroke symptoms at age 14.6 ± 0.7 wks (n=3), while no symptoms developed in SHRSP fed purified diet, and so rats were sacrificed at age 19 weeks (n=3). Body weight was significantly lower at age 14 wks in SHRSP fed chow (261.6 ± 7.5 g) than SHRSP fed AIN93‐G (307.3 ± 4.9 g). In another study, SHRSP rats fed chow with 4 % NaCl developed stroke symptoms by age 15.3 ± 0.5 wks (n=10). These data provide evidence to suggest that dietary composition is a major contributor to the onset of stroke in SHRSP. Further investigations are being carried‐out to determine the specific dietary components of the commercial rat chow that increase incidence of stroke in SHRSP. Funded by NSERC & Atlantic Innovation Fund.