bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Peptide Bound to Major Histocompatibility Complex Allows Visualization of Insulin Secreting Beta Cells in vivo
Authors: Miller Keith Russell , Taft Joseph , Koide Akiko , Johnson Mark , Tisch Roland , Koide Shohei , Collins Edward
Published: November 2023

The breaking of T cell tolerance in autoimmune disease results in selective killing of healthy cells. In Type 1 Diabetes (T1D), autoreactive T cells use their T cell receptor (TCR) to recognize β cells by binding to the β cells’ antigen‐peptide bound to Class I Major Histocompatibility (pMHC) molecules. The interaction of the TCR with the pMHC is required for T1D to develop; however, precise mechanisms and timing of β cell destruction have not been defined. A significant problem in developing T1D therapies and studying its disease initiation and progression is the absence of a noninvasive in vivo β cell imaging agent for early diagnosis and evaluation of potential treatments. To address this problem, we used phage display technology to isolate recombinant antibody fragments (Fabs) that mimic the TCR. Surface plasmon resonance showed that two Fabs, fIGRP and fHA, that target an islet‐specific glucose‐6‐phosphatase catalytic subunit‐related protein (IGRP) peptide and influenza hemagglutinin (HA) peptide respectively, restricted to the histocompatibility‐2 Kd (H2‐Kd) have nanomolar binding affinity. Using immunofluorescence microscopy, both Fabs were shown to successfully localize to β cells on cryopreserved mouse pancreas sections. The Fabs also blocked cytokine production of autoreactive T cells when presented with cognate pMHC in vitro. The ability to generate affinity reagents with high affinity and specificity for pMHC has vast potential for understanding where and when specific autoantigens are presented and by which cell types during the progression of T1D and developing targeted therapies for β cell recovery.

Support or Funding Information

This research was supported by the National Institutes of Health AI088081 (EJC), NIH R01‐GM072688 (SK), the University of Chicago Comprehensive Cancer Center supported by P30‐CA014599, the DANA Foundation (http://www.dana.org), the University of North Carolina at Chapel Hill Center for AIDS Research (CFAR), an NIH funded program P30 AI50410 and a University of North Carolina University Cancer Research Fund pilot project award.
Novel small molecule, WZB117, competitively inhibit GLUT1‐mediated glucose transport to halt cancer growth
Authors: Ojelabi Ogooluwa , DeZutter Julie , Lloyd Kenneth , Carruthers Anthony
Published: November 2023

GLUT1‐mediated cellular glucose transport is required to fuel anaerobic metabolism in proliferating cancer cells. Accordingly, GLUT1 inhibition by small molecules is a viable strategy to halt the proliferation of cancers. However, GLUT1 is presently not targeted therapeutically in cancers because of lack of potent and specific inhibitors. Recently, a novel small molecule, WZB117, was shown to kill lung and breast cancer cells by inhibiting GLUT1‐mediated glucose transport, without affecting non‐tumorigenic cells. Here, we studied the detailed kinetics of WZB117 inhibition of GLUT1, and found that WZB117 inhibits uptake of the non‐metabolizable sugar, 3‐O‐methylglucose, by red blood cells with an inhibition constant of 2.83 μM. Our data show that WZB117 is a competitive inhibitor of GLUT1‐mediated zero‐trans sugar uptake and exchange transport but is a non‐competitive inhibitor of zero‐trans exit. These results, together with our docking studies, suggest that WZB117 binds at or near the exofacial sugar‐binding site of GLUT1. In addition, our preliminary data on the specificity of WZB117 for GLUT1 suggests that, while WZB117 inhibits GLUT1 with a high affinity, it is also a potent inhibitor of the skeletal muscle and adipose specific transporter GLUT4 and the neuronal glucose transporter GLUT3. We conclude that the ability of WZB117 to serve as a tumor‐specific inhibitor derives, not from specificity of transport inhibition but rather, from the absolute dependence of tumor cells on anaerobic metabolism and glucose‐dependent anabolism.

Support or Funding Information

This work is supported by NIH grant DK 44888.
Self activation of IGF1R signaling by cancer cells confers a paracrine metabolic advantage
Authors: Lenz Gal , Hamilton Angelica , Huss Janice , Kane Susan
Published: November 2023

A hallmark of tumors is the ability to gain metabolic advantage that enables them to meet an increasing energy demand as part of their rapid proliferation phenotype. As part of this metabolic advantage, tumors use secreted growth factors and hormones that stimulate glucose uptake and signaling to promote glycolysis and ATP production. t‐Darpp, a truncated isoform of the dopaminergic regulator Darpp‐32, has been described as a mediator of drug resistance and enhanced growth and survival in a variety of cancer types. We now demonstrate that cells stably transfected with t‐Darpp (SK.tDp) have increased growth rate, glycolytic capacity and ATP levels relative to control SK‐Br‐3 cells. The increased growth phenotype is also conferred in a paracrine manner to neighboring SK‐Br‐3 cells grown in co‐culture with SK.tDp cells. Moreover, recombinant t‐Darpp added to the growth medium of SK‐Br‐3 cells conferred the same enhanced metabolic phenotype via a mechanism that appears to involve binding and signal transduction via IGFR1. This same effect was seen in L6 myotubes, a natural target of insulin signaling. We propose a model by which cancer cells are able to increase their metabolic capacity and provide a proliferative advantage through novel insulin‐like hormone activity linked to t‐Darpp and IGFR1 signaling.
Mitochondrial Transfer by Photothermal Nanoblade Restores Respiration in Mammalian Cells with Dysfunctional Mitochondria
Authors: Patananan Alexander Nikolich , Wu Ting‐Hsiang , Sagullo Enrico , Case Dana , Zheng Xin , Li Yanjing , Hong Jason , TeSlaa Tara , McCaffery J. Michael , Niazi Kayvan , Braas Daniel , Koehler Carla , Graeber Thomas , Chiou Pei‐Yu , Teitell Michael
Published: November 2023

The reliable delivery of large cargo into mammalian cells could have profound impacts on cell engineering and medicine. Current techniques, such as electroporation, sonoporation, and microcapillary injection, can deliver DNAs, RNAs, and proteins into cells, but they are limited by cargo size, endosomal cargo degradation, and poor efficiency. To circumvent these problems, we invented a photothermal nanoblade. The nanoblade is a titanium‐coated glass pipet that is placed near a cell membrane and heated by a laser pulse. A resulting vapor bubble generates a transient membrane incision that allows the pressure driven delivery of cargo up to 3 μm in size into cells with high efficiency and cell viability. Here, we evaluated whether the nanoblade could transfer isolated mitochondria into cells to rescue mitochondrial dysfunction. The transfer of MDA‐MB‐453 mitochondria into 143BTK‐ρ0 cells, which lack mtDNA, do not respire, and require uridine supplementation to proliferate, resulted in the emergence of three rescued clones in uridine‐free medium 2 weeks after delivery. Interestingly, clones 1 and 3 had ATP levels, oxygen consumption rates, and ETC complex activities similar to the donor and parent cells, while clone 2 continued to have abnormal levels. qRT‐PCR of genes encoding anaplerotic and catapleurotic enzymes showed that rescue lines 1 and 3 were similar to the 143 BTK‐ parent, whereas clone 2 remained similar to the 143BTK‐ ρ0 cells. This distinction between the three clones was maintained in the metabolic profiling of TCA cycle and cytosolic metabolites by mass spectrometry. In conclusion, the ability of transferring functional mitochondria to cells by the photothermal nanoblade is not only important for basic research studies, but also has potential for therapies targeted at correcting mitochondrial diseases.

Support or Funding Information

UCLA Tumor Immunology Training Grant (Ruth L. #Kirschstein Institutional National Research Service Award # T32 CA 009120)
Calcineurin B Homologous Protein Isoform 2 (CHP2) Expression and Activity Impact Cell Migration and Tumor Formation in Non‐small Cell Lung Cancer
Authors: Wallert Clarice , Buchholz Scott , Provost Joseph J , Wallert Mark A
Published: November 2023

The Na+‐ H+ exchanger isoform 1 (NHE1) is a key regulator of cell proliferation, migration and invasion in cells from a variety of solid tumors. The calcineurin B homologous proteins (CHP1 and CHP2) appear to be essential cofactors to support NHE1 function. CHP1 appears to be expressed ubiquitously in healthy tissue, while CHP2 is predominantly expressed in tumor cells. While both CHP isoforms are highly homologous and bind in nearly identical regions on NHE1, each has been identified to have a distinct impact on NHE1 function. Our research has demonstrated an elevation in CHP2 expression in tumor samples from patients with either adenocarcinoma or squamous cell carcinoma of the lung as well as in a broad range of NSCLC cell lines. We hypothesized that elevated CHP2 expression enhances cell survival and the tumorigenic potential of these cells. To evaluate the role of CHP2 in NSCLC cells we used NCI‐H1299, a carcinoma cell line, as the parent cell line and developed two new cell lines. One of these cell lines lacked CHP2 expression (H1299 CHP2KD) and the other lacked NHE1 expression (H1299 NHE1KD). We evaluated the impact of a low serum environment on CHP2 expression and determined that CHP2 levels increased when H1299 cells are grown in 0.5% serum compared to cells grown in 10% serum. This increased CHP2 expression drives changes that support the cells ability to survive these low serum environments. In Electric Cell‐substrate Impedance Sensing (ECIS) migration experiments in 10% serum, H1299 cells reestablished a confluent monolayer within 18 hours of wounding. In contrast, the H1299 CHP2KD cells migrated at approximately 50% of that rate and the H1299 NHE1KD cells showed extremely limited cell migration. When these experiments were performed in 0.5% serum, the migration rate of the H1299 cells was reduced to about 50% of that seen in 10% serum while the rate of migration in H1299 CHP2KD was reduced to a rate equivalent to the H1299 NHE1KD cells. In cell proliferation experiments, H1299 cells in 0.5% serum grow at a rate equivalent to H1299 CHP2KD cells in 10% serum. Finally, in a soft agar assay, a greater rate of tumor formation occurred for H1299 cells in both 10% and 0.5% serum than either the H1299 CHP2KD or H1299 NHE1KD cells. These data suggest a major role for CHP2 expression in the development and progression of non‐small cell lung cancer.
Evaluation of the in vivo role of Cold‐Inducible RNA Binding Protein (CIRP) in Breast Cancer
Authors: Lujan Daniel A , Ochoa Joey L , Peterson Melanie N , Hartley Rebecca S
Published: November 2023

RNA binding proteins (RBPs) post‐transcriptionally regulate gene expression by associating with the regulatory sequences in the 5′ and 3′ untranslated regions of mRNAs to regulate their stability, translation, and localization. RBPs are often disrupted in cancer, but our current knowledge of their role in regulating cancer‐associated genes is largely based on in vitro studies. This study seeks to determine the in vivo role of cold‐inducible RBP (CIRP), which is overexpressed in human breast cancer, in breast tumorigenesis. In cultured cells, CIRP promotes cell proliferation and survival and inhibits apoptosis, as well as promotes inflammation in vivo, all hallmarks of cancer. We set out to test the hypothesis that CIRP promotes breast tumorigenesis in vivo by crossing a transgenic mouse overexpressing CIRP in the mammary epithelium with the PyMT mouse model of breast cancer. Effects on both early (7 weeks of age) and late (14 weeks) tumorigenesis were assessed. Whole‐mounts of mammary glands from 7‐week mice showed that CIRP/PyMT glands had 50% fewer mammary intraepithelial neoplasias than those from PyMT mice. Consistent with this, histopathological analysis showed decreased mitosis and increased apoptosis in CIRP/PyMT vs. PyMT mammary glands. Late stage tumorigenesis was also inhibited, including slower tumor growth kinetics, smaller tumors and decreased tumor burden (8% CIRP/PyMT vs 21% PyMT). To begin to assess mechanism, mammary glands from 7‐week mice were incubated in medium overnight followed by Luminex cytokine assays on the medium. Results showed a decrease in cytokines that promote inflammation, angiogenesis and metastasis. Altogether results suggest that CIRP inhibits proliferation and promotes apoptosis to suppress early tumorigenesis, potentially via decreasing the protumorigenic inflammatory response.
Crosstalk Between MAP Kinase And Hedgehog Pathways by Direct Phosphorylation of Gli Transcription Factors
Authors: Bardwell Lee , Bardwell A Jane , Wu Beibei , Waterman Marian
Published: November 2023

MAP kinase pathways are hyperactivated in many of the same tumor types in which Hedgehog signaling is deregulated. Indeed, crosstalk between the Hedgehog/Gli pathway and Ras/mitogen‐activated protein kinase (MAPK) signaling pathways occurs in many types of cancer, including pancreatic cancer, melanoma, colorectal cancer, and medulloblastoma, and may contribute to the emergence of clinical resistance to Hedgehog pathway inhibitors (reviewed in [1, 2]). However, the molecular mechanism(s) of this crosstalk are unclear. We have shown that the transcription factors Gli1 and Gli3, which are downstream targets of the Hedgehog pathway, are also efficient substrates of ERK and JNK‐family MAPKs [3]. Here we show that MAPKs phosphorylate Gli1, Gli2 and Gli3 on residues located near the binding site for Sufu, a key negative regulator of Gli function. Furthermore, we show that MAPK‐mediated phosphorylation weakens the binding of Sufu to Gli1‐3. We have mapped the MAPK phosphorylation sites in Gli1, and show that three sites are collectively necessary and sufficient for Sufu release. Cells expressing Gli1 alleles mutated in these residues exhibit perturbed Hedgehog signaling. Hence, we identify a functional mechanism of MAPK‐Hedgehog crosstalk that could contribute to developmental signaling, tumorigenesis and clinical resistance.

Support or Funding Information

This work was supported by NIH‐NIGMS grant P50‐GM76516 and by a grant from the University of California Cancer Research Coordinating Committee
Arsenite activates Hog1 MAPK through an intracellular pathway in Saccharomyces cerevisiae
Authors: Lee Jongmin , Levin David E
Published: November 2023

Arsenite is a toxic metalloid that is abundant in the environment. It is known as a carcinogen as well as a drug for anti‐cancer treatment. In the yeast Saccharomyces cerevisiae, arsenite enters the cell through the aquaglyceroprin Fps1. Control of Fps1 channel activity in response to arsenite involves the MAPK Hog1 of the High Osmolarity Glycerol (HOG) pathway. However, the mechanism by which Hog1 regulates channel activity in response to this stress is not understood. We found that Hog1 is activated by arsenite through an intracellular mechanism, rather than through the canonical MAPK signaling pathway. Activation of Hog1 in response to arsenite is achieved through direct targeting of two tyrosine phosphatases, Ptp2 and Ptp3, by a methylated metabolite of arsenite, monomethylarsonous acid. Because Ptp2 and Ptp3 maintain Hog1 in an unphosphorylated, inactive state, their inhibition results in elevated Hog1 activity. We also found that Hog1 activated in response to arsenite induces closure of Fps1 through phosphorylation of a redundant pair of Fps1 regulators, Rgc1 and Rgc2, in a manner similar to its response to hyper‐osmotic shock. These regulators associate with Fps1 under non‐stress conditions, maintaining the channel in an open conformation. In response to arsenite, activated Hog1 phosphorylates Rgc1 and Rgc2 and induces their rapid eviction from Fps1 and consequent channel closure. However, unlike the response of Hog1 to hyper‐osmotic shock, Hog1 activated by arsenite does not translocate from the cytoplasm to the nucleus and does not drive HOG pathway transcription. We speculate that the different mechanisms by which Hog1 is activated in response to these different stresses plays a critical role in its signaling output.
Specific Inhibition of Smad3 Nuclear Translocation with TAT Fusion Peptides Prevents Profibrotic TGFβ Activity
Authors: Kang Jeong‐Han , Jung Mi‐Yeon , Yin Xueqian , Andrianifahanana Mahefatiana , Hernandez Danielle , Leof Edward B.
Published: November 2023

Transforming growth factor‐β (TGFβ) is the prototype of a family of secreted polypeptide growth factors with key roles in cellular growth and differentiation. The primary mediators of TGFβ action are the Smad proteins, specifically Smad2 and Smad3. Upon receptor activation these 55–60 kDa proteins are phosphorylated (p) by the type I TGFβ receptor and undergo nuclear translocation to function as co‐modulators of gene expression. While the specific roles of Smad2 and Smad3 are being actively investigated, recent findings have shown that while Smad3 is clearly pro‐fibrotic/pro‐carcinogenic, Smad2 can induce anti‐fibrotic/anti‐carcinogenic responses. Thus, approaches designed to target more downstream TGFβ receptor signaling components may provide equivalent efficacy and greater specificity. To that end, as we previously determined that sorting nexin 9 (SNX9) plays an integral role in the nuclear import of pSmad3 (but not pSmad2), we have extended those findings and identified the functional element in SNX9 critical for pSmad3 binding. Furthermore, we show that a TAT‐fusion encompassing this region can act in a dominant manner to block SNX9/pSmad3 binding, pSmad3 nuclear translocation, and subsequent pro‐fibrotic responses dependent upon pSmad3 both in vitro and in vivo.

Support or Funding Information

This work was supported by Public Health Service grants GM‐055816 and GM‐054200 from National Institutes of General Medical Sciences.
Structured RNAs that Manipulate the Translation Machinery
Authors: Kieft Jeff S
Published: November 2023

Translation is a complex process that is subject to precise regulation throughout all of its phases, but the repertoire of mechanisms by which this regulation is achieved remains unknown. We are interested in understanding one particular class of regulation mechanism: how structured RNA elements embedded within mRNAs can alter or regulate translation through direct interaction with the ribosome. Such interactions can drive non‐canonical modes of translation initiation (e.g. cap‐independent or IRES‐driven translation), programmed ribosomal frameshifting, enhancement of the rate of translation, etc. Many of the most useful model systems for understanding how diverse structured RNAs can manipulate the ribosome come from viral RNAs, therefore these have been the focus of much of our research. We employ a combination of structural biology, biophysics, biochemistry, and virology. In this talk, I will present some of our latest findings and efforts to link the structure of a given RNA with its ability to manipulate the translation machinery.

Support or Funding Information

Howard Hughes Medical Institute early Career Scientist Award

National Institutes of Health R01GM081346 & R01GM097333

Cancer League of Colorado
Dissecting Functions of the Turnip yellows virus Suppressor of RNA Silencing P0 in Evasion and Elicitation of Plant Defenses
Authors: Dughbaj Mansour , Valdez Kevin , Wang Ken‐Der , Nguyen Tan Tri , Oza Shyamal Vishnu , Sacco Melanie Ann
Published: November 2023

The Turnip yellows virus (TuYV) protein P0 (P0Tu) is a viral suppressor of RNA silencing (VSR) that targets Argonaute (AGO) proteins for degradation. P0Tu is also recognized in Nicotiana glutinosa accession TW59, in which it elicits hypersensitive response (HR) and resistance to TuYV. We are interested in understanding how P0Tu interacts with the host plant cell as a VSR versus an elicitor of HR. To identify amino acids that are critical for these activities, P0Tu has been subjected to serial deletion analysis and site‐directed mutagenesis at either several conserved sites or by systematic substitutions with the 6 amino acid sequence NAAIRS along the entire length of the coding sequence. We predicted that the modifications could potentially cause loss of VSR activity in Nicotiana benthamiana and/or loss of HR activation in N. glutinosa to dissect these two functions. Mutant clones were co‐infiltrated with GFP into the leaves of N. glutinosa accession TW59 and N. benthamiana to observe for suppression of RNA silencing and induction of cell death. Substitution of two conserved central arginine residues with lysine caused P0Tu to activate more rapid and robust HRs on N. glutinosa. Deletion or mutation of the amino terminus inactivated P0Tu, while modifications within or deletion of the last 22 carboxy‐terminal amino acid residues (227–249) resulted in mutants that maintained VSR activity, but had impaired ability to elicit HR on N. glutinosa, suggesting that P0 activities in suppression of silencing and elicitation of HR may be distinct.

Support or Funding Information

National Science Foundation (NSF) Grant #1122256 to M. A. Sacco.
Exploring the Relationship between Corruption and Food Security Status on a Global Scale
Authors: Helal Gabrielle , Ahmadigheidari Davod , Kosoy Nicolas , Melgar‐Quiñonez Hugo
Published: November 2023

Food insecurity is a global problem that has yet to be properly addressed. Its determinants are part of a greater scheme of food security governance and overall governance. Presence of corruption occurs when there are failures in governance. There are currently no studies exploring corruption and food security, on a global scale, with internationally validated tools. This study aimed to fill this gap in the literature. The main objective was to explore the relation between corruption and food security status on a global scale.

Data from 2014 Gallup World Poll (GWP) were analyzed. The sample included 185,341 individuals. Food security status, the dependant variable, was assessed using the Food and Agriculture Organization's Food Insecurity Experience Scale. Corruption, the independent variable, was measured using the GWP Corruption Index. Several statistical analyses formed the basis of the current work. Cross‐tabs and logistic regression were conducted to evaluate the relationship between socio‐demographic characteristics and corruption on food security, using IBM ® SPSS ® version 23, using the complex samples module.

Descriptive statistics shows that an absence of perceived corruption was significantly higher in food secure population, when compared to food insecure. Women had higher rates of food insecurity than men. Lastly, higher level of education, higher income and full‐time employment were found among food secure population. All of these results were significant.

Findings using a logistic regression model show that food insecurity was significantly higher in a population that perceives corruption (OR 1.192), after adjusting for other variables. Food insecurity was significantly higher among women (OR 1.123). Also, individuals who were unemployed (OR 1.077), or had part‐time employment (OR 1.492) had significantly higher odds of being food insecure. When compared to the high‐income group, low‐income individuals had significantly higher odds of being food insecure (OR 19.498). Finally, in terms of age, food insecurity was higher in the younger population (p=0.03).

The findings of this study help fuel a new approach in the global fight against food insecurity. These findings suggest that amongst diverse population demographics, an absence of corruption has a positive impact on food security. The results of this novel study will promote governmental accountability in regards to corruption, and will contribute to emerging research in the field of food security governance.
The Perceived Food Environment Surrounding Tribal Lands in California: Tribal Member Perspectives
Authors: Chodur Gwen Marie , Kodish Stephen , Antiporta Daniel , Oddo Vanessa , Shen Ye , Jones‐Smith Jessica
Published: November 2023

Objective

To describe and understand the food environment surrounding tribal lands in California and its impact on food choices among Native American tribal members.

Methods

We conducted in‐depth interviews with a sample of Native American parents living in California (N=24). Tribal members were purposively sampled from California's federally recognized tribes by study staff at health clinics and conferences, as well as through word‐of‐mouth referrals. We analyzed data using a modified Grounded Theory approach with Dedoose. Initial descriptive categories were developed based on the study objectives using a deductive approach and additional themes were added as they emerged, using the constant comparative method. We assessed discrepancies between coders using IRR and proceeded with coding once high reliability (IRR= 0.83) was achieved.

Results

Salient themes that were identified included limited food purchasing options; challenges in acquiring food due to distance to a food source and financial constraints; and a negative perception of the food environment. It was common for participants to describe tribal lands as more distantly located from food stores and state that the distance to the closest grocery store was an influential factor in choosing foods to purchase. Interview participants tended to have negative perceptions of the quality of food available in their immediate environment and expressed that the lack of convenient healthy food options limited their ability to acquire and consume healthy food. Many expressed frustration at their experience of wanting to provide healthy food for their families, but being unable to do so because of limitations in affordability and availability. Perceptions about restaurants and fast food outlets were mixed.

Conclusions

Native American parents living on tribal lands in California perceived food availability and purchasing options to place considerable constraints on diet quality that conflicted with the intention to purchase and prepare healthy food. The limitations of the food environment may contribute to the health disparities of this population and should be addressed in interventions.

Support or Funding Information

Supported by the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (4R00HD073327).
Physical Activity and Inactivity and its Association with Overweight and Obesity on Children and Adolescents between 10 to 14 Years Old
Authors: Pantoja Itzayana Yarabetzy , Sandoval Ximena , Talavera Juan Osvaldo , Pérez Marcela
Published: November 2023

Introduction

Physical activity and inactivity have been considered risk factors for developing overweight and obesity. Excess weight occurs when the intake from diet is greater than the energy expenditure.

Objective

Determine the association of physical activity and inactivity and overweight and obesity on children and adolescents from 10 to 14 years old in Mexico City.

Methods

Cross sectional study. We recruited 213 children and adolescents. Weight and height were collected by trained personnel. Physical activity and inactivity were measured with an adapted physical activity and inactivity questionnaire for Mexican students (CAINM).

Results

The prevalence of low weight, normal weight, overweight and obesity was 0.9%,57.7%, 23.9% and 7.4% respectively. The median of sleep time on week days was 8 hours and on weekends 10 hours for both genders. 73.5% of the girls and 81.5% of the boys spent ≥2 h/d in front of a screen. The percentage of girls and boys who use inactive transportation to school (car, bus) was 54.5% and 69.1% respectively. 77.8% of the boys and 72%of the girls practice physical activity. No association was found between sleeping hours on week days, sleeping hours on weekends, time spent in front of a monitor, practice of a physical activity and overweight and obesity on girls and boys. The association between the mode of transport to school and overweight and obesity in boys was OR=4.64 (IC95%=1.45–14.83), in girls, there was no significant results.

Conclusions

Despite no association was found between the time spent in front of a monitor, practice of a physical activity and overweight and obesity in girls and boys, the hours a day spent in front of a screen by most children and adolescents exceed the international recommendations (≥2 hours per day). The major finding of this research was that the use inactive transportation to school is a risk factor for overweight and obesity in boys. It is important to take actions that promote the use of active transportation to school (walk, bicycle)because it is a simple way to increase the physical activity.
Added Sugars in the Diet Are Positively Associated with Mean Arterial Pressure and Systolic Blood Pressure in Older Adults
Authors: Chai Sheau C , Davis Kristina , Wright Regina S , Pohlig Ryan , Saltzgiver Julia , Caulfield Alexandra , Falk Danielle
Published: November 2023

Recent evidence suggests that added sugars in the diet have been associated with higher risk of high blood pressure. However, there is a paucity of such research in older adults. Epidemiological studies also support that rich‐fruit diet is associated with lower blood pressure. Hence, the present study examined the relationship between added sugar and fruit consumption, mean arterial pressure and blood pressure in older adults. A cross‐sectional study was conducted that included 128 men and women aged 65–80. Dietary intake was assessed using a food frequency questionnaire. Anthropometric and blood pressure measurements were measured. Partial Pearson correlations were run to examine the association between added sugar and fruit consumption, mean arterial pressure and blood pressure, after adjusting for body mass index. Our findings indicate that added sugar was positively correlated with both mean arterial pressure (r = 0.214; p = 0.017) and systolic blood pressure (r = 0.233; p = 0.009). Overall fruit consumption was inversely associated with mean arterial pressure (r = −0.181; p = 0.044) and diastolic blood pressure (r = −0.206; p = 0.021) levels. More importantly, intake of solid fruits, but not juice, was inversely associated with mean arterial pressure (r = −0.281; p = 0.001), and systolic (r = −0.199; p = 0.026) and diastolic (r = −0.304; p = 0.001) blood pressure levels. Findings suggest a need for reduced intake of added sugars, but increased intakes of solid fruits among older adults to promote healthy blood pressure. Future studies are warranted to investigate the relationship of added sugar to vascular biomarkers.
Metabolism of uniformly labelled 13C‐eicosapentaenoic acid and 13C–arachidonic acid during healthy aging
Authors: Léveillé Pauline , Chouinard‐Watkins Raphael , Cunnane Stephen , Brenna J. Thomas , Plourde Mélanie
Published: November 2023

Long chain polyunsaturated fatty acids (LC‐PUFA) are involved in signalling pathways that control a wide range of bodily functions, notably inflammatory response. We previously gave a single dose of 13C‐docosahexaenoic acid (13C‐DHA) to six young (~25 yrs old) and six older (~75 yrs old) participants and we found that 4 h after the tracer intake, 13C‐DHA was fourfold higher in the plasma of older participants than the young. Because previous studies reported that EPA (eicosapentaenoic acid) and AA (arachidonic acid) concentrations are age‐dependant, we sought to better characterize the kinetics of these two fatty acids between young and older participants.

Objective

To determine the kinetics of 13C‐EPA and 13C‐AA in young and older participants.

Method

Six young (18–30 yrs old) and six elderly (≥ 70 yrs old) healthy participants were recruited. The study is designed in three blocks of one month: 13C‐EPA follow‐up, wash‐out and 13C‐AA follow‐up. Each participant will orally consume a single oral dose of 35 mg of 13C‐EPA, and after the wash out a 50 mg dose of 13C‐AA. Fasted blood and breath samples will be collected before breakfast (baseline) and thereafter 2 h, 4 h, 6 h, 12 h, 24 h, 7 d, 14 d, 21 d and 28 d after the tracer intake. Breath samples will be collected in triplicate.13C enrichment in breath 13CO2 was measured by isotope ratio mass spectrometry.

Preliminary results

To date, two young and four elderly participants have started the study. Mean age of the young and the elderly is 24 ± 4 and 75 ± 2 yrs old, respectively. Weight and body mass index were not different between the two groups. At baseline, there was no difference in plasma triglycerides, HDL, LDL and total cholesterol between the two groups supporting that the elderly are metabolically healthy. Cumulative β‐oxidation of 13C‐EPA over 7 days reached 40% in both groups. 13C‐EPA and 13C‐AA will be analyzed in the plasma of both groups. Aging is associated with low‐grade inflammation and EPA and AA are precursors of anti‐ and pro‐inflammatory molecules, respectively. Hence, this study will provide new insight into physiological modifications of these fatty acids metabolism associated with aging and could open new directions for research in this area.

Support or Funding Information

Quebec Network for Research on Aging. Pauline Léveillé is supported by a postdoctoral fellowship from the department of medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke.
Possible Nutritional Etiology of Osteosarcopenic Obesity Syndrome
Authors: Inglis Julia E , Jafarinasabian Pegah , Gilman Jenifer C , Kelly Owen Joseph , Ilich Jasminka Z
Published: November 2023

Osteosarcopenic obesity (OSO) is a recently identified syndrome characterized by simultaneous presence of osteopenia/osteoporosis, sarcopenia, and increased adiposity (either as overt overweight or fat redistribution and infiltration into bone and muscle). Our objective was to examine possible dietary macro and micro nutrient patterns, possibly leading to OSO. We analyzed 2011–2012 NHANES data (as a proxy for Western‐type diet) for macro and micro nutrients in older women to determine possible relevant nutritional deficiencies and/or excesses. The data revealed reduced energy intake with aging, despite the weight gain. This suggests that decrease in higher metabolically active tissue, especially muscle mass (sarcopenia), coupled with increased adipose tissue (obesity) and overall lower metabolic rate requires less energy to maintain/gain body weight. Protein intake (as % of energy) was below recommendations, while total fat (as % of energy) remained stable, but EPA and DHA were low. Carbohydrate intake was higher than recommendations and simple sugars contributed to more than 50% of total carbohydrate intake. Women were insufficient in Ca, Mg, and K, vitamins A, D, E, K, C and B6, but in excess of minerals P, Na and Fe, and possibly B12, niacin and riboflavin. Although there is a limited knowledge as to how each separate nutrient behaves within the current nutritional environment, our analysis suggests that the typical Western‐diet nutrient composition, for both macro and micro nutrients may not promote healthy aging and may be contributing to the low‐grade chronic inflammation and ultimately development of OSO. In conclusion, the combination of low protein, high simple carbohydrates, and deficiencies of Ca, Mg and K and excess of P, Na and Fe, and deficiencies of fat soluble vitamins, may be associated with lower bone mass, sarcopenia and increased/redistributed adiposity, and therefore lead to OSO.

Support or Funding Information

No funding source.
BODY COMPSOTION AND DIETYARY INTAKES IN CHILDREN WITH CEREBRAL PALSY ACCORDING TO OBESITY DEGREE
Authors: Kim Hyo‐Jung , Yim Jung‐Eun
Published: November 2023

The major obstacles to the development of children with cerebral palsy (CP) are related with inadequate nutrient intake. This study aims to reveal meal‐related factors affecting nutritional status and development of CP by conducting and evaluating surveys on dietary intake of children with cerebral palsy considering obesity degree.

This study conducts a survey of 16 children with cerebral palsy. The children are categorized into underweight group, normal weight group, and obesity group. The general characteristics and motor disturbance were evaluated by specialist in rehabilitation. The body composition was measured by bioimpedance method. The feeding disturbance, eating habits, dietary intake, and intake patterns by foods were examined by registered dietitian.

The underweight children with CP had higher degree of motor disturbance and feeding disturbance (p<0.05). The percentage of body fat were 12.5%, 32.1%, and 44.5% in underweight, normal, and obese CP children, respectively (p<0.05). The visceral fat were 28.0cm2, 36.4 cm2, and 75.5 cm2 in underweight, normal, and obese CP children, respectively (p<0.05). In the eating habits, the underweight children with CP had unbalanced meals, and those in obesity group tend to have larger and faster intake meals. The obese CP children had eating problems such as overeating and unbalanced diet (p<0.05). The intake amounts of magnesium, vitamin D, and calcium were deficient in CP children.

Our result suggested that obesity degree affected disability, body composition, and dietary intakes in children with CP. It is necessary to emphasize the adequate dietary intake and nutrients (magnesium, vitamin D, and calcium) in CP children, especially in underweight children with CP. The obese children with CP had severe abdominal obesity, and were needed change of eating habits.
Serum Lipids Profile of Growing Rats Feed with Different Sources of Lipids
Authors: Perris Paula , Inés Fernandez , Mambrin Maria Cecilia , Slobodianik Nora , Feliu Maria Susana
Published: November 2023

Introduction

Diet lipid profile is important to prevent chronic diseases and improve the quality of life of individuals.

Objective

analyze the effect of different sources of dietary lipids on sera triglycerides (TG), total cholesterol (TC) and fatty acid profile of growing rats.

Methods

weanling Wistar rats were fed during 40 days with experimental diet containing: 15 Kcal of lipids % (F%) provided by butter (B group) and olive oil (O group). Control group(C) received diet according to AIN’93 (soy oil and F%=15). Sera levels of TG and TC were determined by enzymatic‐colorimetric method. Diets, serum fatty acids profiles were determined by gas chromatography. Statistical analysis used ANOVA and Dunnett/Kruskal‐Wallis as post tests (*p<0.01).

Results

Sera (mean±SD, mg/dL) TG B15=122.9±28.4*; O15=94.6±23.7; C=62.2±27.3; TC B=65.7±8.8; O=69.5±7,0; C=62.1±9.6. Results of fatty acids expressed as % Area (*p<0.01) were: PALMITIC B=20.66±1.86* O=19.44±2.05 C=16.08±2.15 OLEIC B=19.26±1.97* O=20.42±3.51* C=11.29±2.27 LINOLEIC B=5.71±3.35* O=8.40±0.96* C=18.50±3.31 LINOLENIC B=0.33±0.16* O=0.35±0.15* C=0.81±0.22.

Conclusion

TG were statistical higher in B compared with C. Experimental groups B and O showed higher sera oleic acid levels with lower linolenic and linoleic levels compared to C. Conclusions: The increase of TG would be a consequence of the type of lipid received. The results of sera fatty acids suggest that it was exacerbated ω9 family with diminution of essential fatty acids. The sources of dietary lipids provoked changes in sera fatty acids profiles.

Support or Funding Information

Supported by UBACyT 20020120200068.
Protein Quantity, Quality, and Distribution Have No Effect on Daily Appetite Control, Satiety, or Free living, Ad libitum Food Intake during Energy Balance in Healthy, Overweight Women
Authors: Shafer Rebecca
Published: November 2023

Background

Acute, single‐meal trials have illustrated postprandial improvements in appetite control and satiety following the consumption of single, high‐protein (HP) vs. standard‐protein (SP) meals. However, it is unclear as to whether these improvements occur across the day when protein is consumed at each eating occasion. Other factors, including protein quality and distribution, may also influence the protein‐related benefits.

Objectives

To examine the effects of protein quantity, quality, and distribution across the day on appetite control, satiety, and ad libitum food intake during energy balance (EB) in healthy, overweight women.

Methods

Seventeen women (age: 33±1y; BMI: 27.8±0.1kg/m2) completed the following randomized controlled‐feeding, cross‐over design study. Participants consumed 4 EB diets (~2000 kcal/d) containing SP (15% of energy from protein; 76±1g protein/d) or HP (25% of energy from protein; 126g protein/d). The SP diets contained either all plant proteins (PLANT) or a combination of beef and plant proteins (BEEF), in which the protein was evenly distributed throughout the day (EVEN). The HP treatments were BEEF and were provided as an EVEN or uneven distribution (UNEVEN) pattern – with 15% of daily protein consumed at breakfast, 20% at lunch, and 65% between dinner and the evening snack. All food was provided for 7 days/diet. On day 6 of each pattern, participants completed a tightly‐controlled 12‐h testing day consisting of questionnaires assessing perceived hunger, fullness, desire to eat, prospective food consumption (PFC), and food cravings. On day 7, protein intake was held constant but carbohydrate and fat‐rich foods were provided ad libitum at each meal and snack.

Results

Protein quality, quantity, and distribution had no effect on daily hunger, fullness, desire to eat, or PFC. In addition, no differences in food cravings were detected between treatments. By design, daily protein intake was greater following the HP vs. SP diets (p<0.05). However, ad libitum carbohydrate and fat intake was not different between treatments.

Conclusions

These data suggest that protein quantity, quality, and distribution do not significantly influence eating behavior during energy balance in healthy, overweight women.

Support or Funding Information

The Beef Checkoff
Effects of folic acid supplementation in Alzheimer diseases‐associated mitochondrial pathology and genomic expression profiles in the 3xTg‐AD mice model
Authors: Jheng Yu , Chen Ta‐Fu , Chou Chien‐Yu , Chiu Ming‐Jang , Hsieh Rong‐Hong , Wang Chia‐Chuan , Huang Rwei‐Fen S.
Published: November 2023

Aims of the study were to evaluate effects of folic acid supplementation in Alzheimer diseases‐associated mitochondrial pathology and genomic expression profiles using the 3xTg‐AD mice model. Non‐transgene mice C57BL/6 mice (non‐Tg control) and 3xTg‐AD mice at 11 months were fed with the diet in the absence and presence of folic acid supplementation (FS: in drinking water and by folate gavage) for 4 months. The data revealed that FS for 4 months significantly ameliorate AD‐induced pTau expression, apoptotic signaling, mitochondrial abnormalities in fission and fusion (Mfn1 and Drp1 protein) and mitochondrial pathology in neuron myelination of AD mice. Brain folate was significantly and inversely correlated with Aβ40 deposition. Hepatic folate levels were significantly correlated with improved slope of cognition learning. Microarray analysis revealed that genetic expression profiles of AD mice hippocampus in complement and coagulation cascades, neuroactive ligand‐receptor interaction, long‐term depression, focal adhesion and Wnt signaling pathways were significantly modulated by FS, which may play the important role of AD‐associated mitochondrial pathology and neuron demyelination.
Anti‐Proliferative and Anti‐Inflammatory Action of Blueberry Polyphenols in HIG‐82 Rabbit Synoviocytes
Authors: South Sanique , Lucero Jacquelynn , Imrhan Victorine , Prasad Chandan , Vijayagopal Parakat , Juma Shanil
Published: November 2023

Rheumatoid arthritis (RA) is an autoimmune and a chronic inflammatory disease resulting in joint destruction and disability in the adult population. The etiology of this condition is not well understood and presently there is no cure for this disease. The accumulation and proliferation of fibroblast‐like synoviocytes may be involved in cartilage destruction. Proinflammatory cytokines such as interleukin 1‐beta (IL‐1β) and tumor‐necrosis factor‐alpha (TNFα) are implicated in the progression of RA. Both in vitro and in vivo studies support an anti‐inflammatory role of dietary polyphenols, the bioactive constituents found in fruits and vegetables. Hence we investigated the anti‐proliferative and anti‐inflammatory role of blueberry polyphenols (BBP) using rabbit synoviocytes stimulated with TNFα. BBP significantly decreased cell proliferation (p < 0.05) in a dose dependent manner reaching 34.1% vs Control at a dosage of 200mg/ml. In‐Cell ELISA analysis for cyclooxygenase (COX‐1) and COX‐2 showed a significant decline with increasing doses of BBP. Post TNFα stimulation, cells treated with BBP resulted in decreases in IL‐1β and Nuclear Factor Kappa B (NF‐κB) protein expressions. Our results suggest that down‐regulation of proinflammatory cytokines and transcription factor NF‐κB by naturally‐occurring bioactives such as blueberry polyphenols may be an appropriate therapeutic strategy for rheumatoid arthritis.

Support or Funding Information

Partially supported from Human Nutrition Research Funds at Texas Woman's University. Lyophilized blueberry powder was generously provided by the US Highbush Blueberry Council.
Screening Acerola (Malpighia emarginata) Genotypes for Protection against LPS‐Induced Inflammation in Macrophage Cells and Selectivity to Cyclooxygenase‐2 (COX‐2) Activity
Authors: Bhargava Prerna , Nair Vimal , Bang Woo Young , Schreckinger Maria Elisa , Alves Ricardo Elesbao , Cisneros‐Zevallos Luis
Published: November 2023

Acerola has been extensively studied for its antioxidant, antimicrobial, anti‐inflammatory, anticancer, antigenotoxic and antihyperglycemic properties. The aim of this investigation has been to study the putative anti‐inflammatory mechanism of various genotypes of acerola (fruit and leaves) fractions and project acerola as natural substitute for aspirin and ibuprofen.

Conventionally, NSAID has been known to have preventive action against acute and chronic inflammation by inhibiting cyclooxygenases. Previous studies have illustrated that phytochemicals like alkaloids, terpenoids, flavonoids, curcumin and phenolics have COX inhibitory action. However, there is a necessity to seek for a naturally occurring selective inhibitor of COX‐2, that can modulate inflammation and could overcome the limitations of drugs like aspirin. Aspirin is known to form an irreversible and non‐competitive binding to COX which proves to be a potent cardiovascular protective agent. On the other hand, irreversible binding inhibits blood platelet aggregation.

For characterization of phytochemicals that are responsible for scavenging and anti‐inflammatory effect of acerola a comparative study using TLC and LC‐MS was employed. Phytochemicals of acerola were extracted using two different solvents ‐ methanol and methanolic/ acetone/ water. Each solvent extracted different category of compounds. One of the two fractions included polyphenols and other one was polyphenols/terpenoids. The two fractions were explored to elucidate mode of action for different acerola genotypes in an in‐vitro system of macrophages. Results indicated with p‐ value < 0.05, which means that the methanolic fractions of acerola exhibited suppression of ROS and partial decrease of nitric oxide levels in LPS‐stimulated RAW264.7 macrophage cell line. This fraction also demonstrated inhibition of enzyme expression of COX‐1/2. Moreover, with p‐ value < 0.05, BRS‐238, a ripe fruit genotype of acerola, displayed a selective action against COX‐2. This confirms that acerola's anti‐inflammatory action is through selective inhibition of COX‐2.