bluuebunny/crossref_metadata_2025 huggingface dataset:
NADPH oxidase 1 (Nox1)‐mediated Reactive Oxygen Species generation stimulate gut homeostasis and restitution
Authors: Darby Trevor , Jones Rheinallt
Published: June 2021

It is well established that physiological generation of low levels of ROS act as critical second messengers in multiple signaling pathways. These include the regulatory networks that control growth and differentiation in disparate biological systems, including the gut of many metazoans. However, the molecular mechanism of ROS production within the intestine is unknown. Recent reports have shown that the ROS‐generating enzyme NADPH oxidase 1 (Nox1) is highly expressed by colon epithelia. Here, we report that ROS generation by Nox1 in the murine colon is necessary for normal intestinal stem cell proliferation and differentiation. Gut epithelial‐specific Nox1‐null mice exhibited increased cell‐death at the base of the crypt, altered differentiation, and slower recovery rates following gut injury. Together, these results implicate Nox1 as an essential protein in epithelial cell homeostasis and response to injury, and reveal a novel mechanism for the maintenance of intestinal tissue structure.
The Influence of Neddylation on the Mucosal Inflammatory Response
Authors: Curtis Valerie , Ehrentraut Stefan , Campbell Eric , Glover Louise , Bayless Amanda , Kelly Caleb , Kominsky Douglas , Colgan Sean
Published: June 2021

Recent work has revealed a central role for neddylation (the conjugation of a Nedd8 protein to Cullin‐proteins) in the induction of the NF‐κB pathway (via Cullin‐1) and stabilization of hypoxia‐inducible factor (HIF, via Cullin‐2) during inflammatory responses. Our recent work indicated that pharmacological stabilization of HIF with the neddylation inhibitor MLN4924 significantly abrogated colitis endpoints in mice. In the present studies, we addressed the contribution of Cullin‐1 neddylation and NF‐kB signaling to mucosal inflammatory responses in vitro and in vivo. Initial in vitro studies using T84 intestinal epithelial cells revealed that MLN4924 prominently induces the deneddylation of Cullin‐1. Parallel western blot analysis and luciferase reporter assays revealed MLN4924 as a potent inhibitor of intestinal epithelial NF‐kB. In vivo administration of MLN4924 (3mg/kg/day) in a TNBS colitis model significantly increased disease severity. Indeed, MLN4924 resulted in increased weight loss and colon shortening as well as increased mortality early in the inflammatory response (day 2). Histologic analysis of the colon revealed that neddylation inhibition results in increased tissue damage and significantly increased mucosal apoptosis as determined by TUNEL staining, particularly within the epithelium. These studies reveal that Cullin‐1 neddylation, and most particularly NF‐κB signaling, is protective during mucosal inflammatory responses. We conclude that Cullin neddylation fine‐tunes the mucosal inflammatory response in vitro and in vivo.
Loss of Slc26a9 induces an early gastric malignancy in mice and is associated with gastric cancer in humans
Authors: Liu Xuemei , Ran Lidan , Li Taolang , Seidler Ursula , Tuo Biguang
Published: June 2021

Background

Slc26a9 deficiency causes a series of precancerous changes in murine stomach at 5 weeks of age (Xu et al., PNAS 2008), suggesting that Slc26a9 may be involved in gastric malignancy with increasing of age. Aim and

Methods

To understand how Slc26a9 deficiency promotes gastric carcinogenesis in mice and humans, histopathological and immunohistochemical analysis were performed in Slc26a9‐/‐ and WT stomach at 15 months of age. Slc26a9 mRNA and protein expression were measured by qPCR and Western‐blot in human normal gastric epithelium, gastric cancer tissues and cell lines.

Results

Absence of Slc26a9 in the mouse caused epithelial cell aberrations that mimicked most of those seen in progression of human gastric cancer including oxyntic atrophy, chronic inflammation independent of Hp infection, intestinal metaplasia, TFF2‐expressing metaplasia, and ultimately high‐grade intraepithelial neoplasias. Accompanying with stimulated proliferation and suppressed apoptosis in gastric epithelial cells. human gastric cancer tissues and cell lines displayed significantly decreased of Slc26a9 mRNA and protein expression when compared with health control. Immunohistochemical analysis of human superficial gastritis, atrophic gastritis, adenomatous polyp and gastric cancer indicated progressive decrease in Slc26a9 expression.

Conclusions

Slc26a9 deficiency leads to spontaneous premalignant and malignant lesions in the gastric epithelia of mice and it can be as a useful model to study gastric cancer. Slc26a9 may be a candidate tumor suppressor gene in development and progression of human gastric cancer.
Myeloid derived suppressor cells as mediator of PAF‐R dependent systemic immunosuppression and melanoma tumor growth
Authors: Thyagarajan‐Sahu Anita , Travers Jeffrey , Sahu Ravi
Published: June 2021

Previously, we have shown that ultraviolet B (UVB) irradiation induces systemic immunosuppression and augments the growth of experimental melanoma tumors via Tregs in a PAF‐R dependent manner. Myeloid derived suppressor cells (MDSC) are heterogeneous group of immature myeloid cells that are known to suppress host anti‐tumor immunity. However, its role in PAF‐R dependent systemic immunosuppression and melanoma tumor growth have not been investigated. The current studies were designed to determine if MDSC that are characterized by CD11b+Gr1+ cell markers (in mouse), mediate PAF‐R‐mediated effects. Using our well characterized models of contact hypersensitivity, we demonstrate that depletion of MDSC by anti‐Gr‐1 Ab abrogates PAF‐R agonists mediated systemic immunosuppression. As UVB or systemic PAF‐R agonists enhance CD11b+Gr‐1+ cell population in lymphoid organs, next studies investigated the role of MDSCs in PAF‐R‐dependent melanoma tumor growth. We observed that depleting Gr‐1+ cells, blocked both UVB and CPAF‐induced enhanced growth of melanoma tumors in WT mice. Interestingly, PAF‐R deficient mice showed substantial reduction in melanoma tumor growth by anti‐Gr‐1 Ab. These findings indicate that MDSC play crucial roles in PAF‐R agonists mediated systemic immunosuppression and melanoma tumor growth. Nevertheless, the crosstalks between MDSC and Tregs in PAF‐R dependent effects are under investigation, these studies provide novel insights into the mechanisms of PAF‐R induced effects.
Subarachnoid Hemorrhage (SAH) Triggers Arrest of Cerebral Spinal Fluid (CSF) Circulation
Authors: Federley Richard , Golanov Eugene , Wong Stephen , Britz Gavin
Published: June 2021

SAH, blood accumulation in subarachnoid space (SS), is caused by rupture of intracranial aneurisms or by TBI. CSF circulating throughout SS and brain parenchyma forms glymphatic pathways for waste removal. We explored alterations to CSF circulation following SAH in C57BL mice at various time after perforation SAH. Fluorescent microspheres (μS, 0.02, 1.0 mm) were injected into the cisterna magna (CM). One hour later, their spread across the brain was monitored using in vivo multiphoton or ex vivo fluorescence microscopy. In naive mice, from CM μS spread to the brain stem, paraarterially along Willis circle, and further along middle cerebral artery and the ventral surface vessels toward the olfactory bulb. Caudally μS spread down the spinal cord. One hour after SAH, μS were confined to the CM and brain stem region limited by the rostral pons border indicating significant CSF flow impairment. The number of μS distributed to the spinal cord was also greatly reduced. Four days post SAH CSF flow remained arrested, indicating long‐lasting CSF flow blockade and its independence from acute elevation of intracranial pressure. In vivo examination of vasculature before and after SAH showed significant vasoconstriction as early as 15 minutes post SAH, and suppression of the slow high amplitude vasomotion. The mitigation of vasomotion, in conjunction with the vasoconstriction may contribute to the CSF flow blockade. Acute and prolonged arrest of CSF flow may play an important role in SAH‐induced brain pathology. Supported by The Ting Tsung and Wei Fong Chao Center for BRAIN, John S Dunn Research Foundation, and the Oden Brain Aneurysm Research Foundation.
Persistence of Memory and Prion Mechanisms: A Perspective
Authors: Kandel Eric
Published: June 2021

Long‐term memory for behavioral sensitization is synapse specific and requires local protein synthesis at the activated synapse. Kausik Si next found that local protein synthesis is regulated by a neuron‐specific isoform of cytoplasmic polyadenylation element binding protein (CPEB). Aplysia CPEB protein is a regulator of protein synthesis that upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long‐term facilitation.

Recently we have extended this work in two directions:

1) We found CPEB‐3 as a homolog of ApCPEB in the mammalian brain and found that CPEB‐3 is activated by Neuralized, an ubiquitin hydrolase.

2) We next found for a new class of prions in the mammalian brain, and found a completely new candidate – TIA (T‐cell intracellular antigen). TIA has classic prion properties in yeast and serves as part of the cellular response to systemic stress. TIA serves as a sex‐specific protective factor in PTSD and does so in female mice only.

In my talk I will to provide an overall view of the emerging biology of functional prions and the various roles of these prions in brain and behavior.
Therapeutic Strategies for Restoring Neural Circuit Function in Rett Syndrome
Authors: Katz David
Published: June 2021

Rett syndrome (RTT) is a severe neurodevelopmental disorder with autistic features caused by loss‐of‐function mutations in the gene encoding methyl‐CpG‐binding protein 2 (MeCP2; Amir et al., Nat. Genet., 1999). Evidence from Mecp2 mutant mice indicates that neurological dysfunction in RTT is associated with abnormalities in the structure and function of brain microcircuits, including altered expression of synaptic proteins and dendritic spine defects, resulting in excitatory/inhibitory synaptic imbalance. However, the specific nature of these abnormalities varies considerably among brain regions. For example, forebrain regions exhibit reduced neuronal activity (Kron et al., J. Neuroscience, 2012) associated with decreased excitatory synaptic drive (reviewed in Katz et al., 2012). In contrast, brainstem regions such as the nucleus solitarius exhibit synaptic hyperexcitability (Kline et al., J. Neuroscience, 2010; Kron et al., J. Neuroscience, 2012). Taking this heterogeneity into account will be critical for designing molecular therapies aimed at restoring normal functional connectivity and neurological function in RTT patients.

This presentation will focus on preclinical development of potential RTT therapies targeting two different neurotransmitter/neuromodulator systems; glutamatergic signaling through NMDA receptors (Kron et al., J. Neuroscience, 2012) and brain derived neurotrophic factor (BDNF) signaling through the TrkB receptor, respectively (Kron et al., J. Neuroscience, 2014). Our data indicate that both systems can be effectively manipulated to reverse core features of murine RTT in symptomatic Mecp2 mutants. Supported by NINDS, Rett Syndrome Research Trust, Autism Speaks and AstraZeneca.
Convergence and extrusion driven by non‐muscle myosin II are required for normal fusion of the mammalian secondary palate.
Authors: Bush Jeffrey , Kim Seungil
Published: June 2021

Fusion of two distinct embryonic prominences to form a single continuous structure occurs in numerous developmental contexts and typically requires integration of two epithelia and subsequent removal of that intervening epithelium. During fusion of the mammalian secondary palatal shelves, the medial epithelial seam (MES) is removed to form a continuous secondary palate with mesenchymal confluence, but the cellular mechanisms remain incompletely understood. Three main hypotheses for how this occurs have been proposed. Whereas considerable investigation has been made into epithelial to mesenchymal transition (EMT) and programmed cell death of the intervening epithelium as potential cellular mechanisms, the contribution of other cellular dynamics of the intervening epithelium has not been directly evaluated. Using confocal live imaging, we have now directly observed the cellular processes underlying tissue fusion in the palatal shelves. We find that convergence of a multi‐layered epithelium into a single‐layer epithelium is an essential early step driven by cell intercalation and is concurrent to orthogonal displacement of epithelial cells. Surprisingly, we find that epithelial cell extrusion, a process in which cells are surrounded and squeezed from an epithelium in an actomyosin contractility‐dependent manner functions in the removal of the MES during palate fusion. Functional studies in mice indicate that these processes require an actomyosin contractility pathway involving Rho kinase (ROCK) and myosin light chain kinase (MLCK), culminating in the activation of non‐muscle myosin IIA (NMIIA). Together, these data indicate that actomyosin contractility drives cell intercalation and cell extrusion during palate fusion and suggest a general mechanism for tissue fusion in development.
A Genetic Model to Understand Integration During Skull Development and Etiology of Craniofacial Disorders
Authors: Harris Matthew , Henke Katrin
Published: June 2021

The skull is a complex structure. It is comprised of a large number of skeletal elements that are derived from diverse embryological origins and require signaling from numerous tissues to ensure proper development. The integration of the skeletal elements of the skull and their coordinated growth is essential for normal development and disruption of these processes can lead to severe dysmorphology and function. However, little is known about how developmental integration in the skull is manifest nor how such regulation may underlie disease phenotypes. We capitalize on the zebrafish as a genetic model to understand skull development. We have performed systematic large‐scale mutagenesis screens for genes that regulate form of the adult skull. One particular class of mutants causes inappropriate fusion between the bones of the skull roof similar to craniosynostoses in children. Craniosynostosis is a genetically heterogeneous disorder with only about 15% of cases having a known genetic cause. We have identified the altered gene in several of our zebrafish mutants and the function of these genes point to the role of the extracellular matrix (ECM) and its signaling in regulation of suture patency. We hypothesize that a common mechanism shared among cases of premature fusion is differential regulation of maturation of the ECM. Using our mutant models in the zebrafish, we are systematically identifying the genes controlling suture patency. Additionally, by use of mass spectrometry, we have defined protein signatures of fused and patent sutures in our mutant fish models. Direct comparison between our mutant models and that of affected sutures from patients with craniosynostosis, suggests ECM protein candidates whose maturation is associated with suture fusion and regulation of skull form.
Why study muscles: bringing together anatomy, evolution, development, genetics, birth defects and medicine
Authors: Diogo Rui , Smith Christopher , Ziermann Janine
Published: June 2021

The results of recent comparative, Bayesian and parsimony‐based cladistic analyses, developmental and regenerative studies of muscles of humans, other primates, and other chordates show that muscles provide particularly useful data for phylogenetic, evolutionary, and developmental analyses. Importantly, the inclusion of soft tissue‐based information in such studies allows researchers to address evolutionary and developmental questions that are not tractable using molecular or skeletal evidence alone. Here we address long‐standing questions about the evolutionary history of modern humans and other chordates, focusing on: 1) the developmental and evolutionary origins of the head, neck, pectoral and forelimb muscles; 2) notions of purpose and progress in evolution and the parallelism between ontogeny and phylogeny; 3) the relationship between trisomies, ‘atavisms’, evolutionary reversions and developmental constraints; 4) the tempo and mode of primate and human evolution (e.g., modularity and ontogenetic constraints); 5) the relationship between modern human anomalies/variations, digit loss/gain, muscle changes and homeotic transformations; 5) similarities and differences among the hind and forelimb structures of modern humans (e.g., serial homology and homoplasy); and 6) the variations and anomalies in the musculature of modern humans and their medical implications.
Dendritic Spine Ultrastructure in Fragile X syndrome: Evidence for Narrower Neck Widths in Dentate Gyrus Granule Cell Neurons of the Hippocampus
Authors: Nahirney Patrick , Weiser‐Novak Samuel
Published: June 2021

Fragile X Syndrome (FXS) is a prevalent monogenic disease that presents neurological abnormalities including learning/memory deficits, autism and epilepsy. The Fmr1 gene ‐ transcriptionally silenced in FXS ‐ normally encodes the Fragile X Mental Retardation Protein (FMRP), of which its function is still obscure, but has been shown to localize at dendritic spines of cortical neurons. In an attempt to understand its role, dendritic spines in the dentate gyrus (DG) and cornu ammonis 1 (CA1) hippocampal regions of 21 day FMRP knockout (KO) mice were analyzed and compared to wildtype (WT) littermate controls using electron microscopy. Spines continuous with a parent dendrite were only included in our analyses. There were no significant differences in spine head diameters (DG: 0.529 ±0.014 vs 0.524 ±0.016; CA1: 0.515 ±0.014 vs 0.524 ±0.014µm), postsynaptic density lengths (DG: 6.18 ±0.85 vs 5.69 ±0.30; CA1: 7.55 ±0.87 vs 6.96 ±0.33µm/100µm2) or spine neck lengths (DG: 0.485 ±0.019 vs 0.457 ±0.016; CA1: 0.425 ±0.017 vs 0.421 ±0.015µm) in KO vs WT mice. Spine neck diameters, however, were significantly narrower in the DG of FMRP KO mice (0.193 ±0.0062 vs 0.167 ±0.0064µm) whereas no significant differences were observed in the CA1 (0.162 ±0.0049 vs 0.161 ±0.0061µm). Estimated resistance provided by narrower spine necks in the DG revealed a ~1.7 fold increase in the resistivity of spines. Taken together, these findings suggest that FMRP plays a role in granule cell neuron spine neck structure and may influence signal propagation in a regionally‐specific manner in the hippocampus.
Effects of Developmental Hyperserotonemia in the Rat Dentate Nucleus Neuronal Morphology
Authors: Hough Lyon , Segal Solomon
Published: June 2021

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social cognition and disordered communication. Furthermore, abnormalities in basic motor control and motor learning, are common in ASD. These have been attributed to a possible defect in the pre‐ and postnatal development of specific neural networks including the dentate‐thalamo‐cortical pathway, involved in motor learning, automaticity of movements, and higher cognitive functions.

The most consistent neurochemical finding reported in autism is an observed 50‐70% increase in platelet serotonin. Occurring in 30% of autistic subjects, developmental hyperserotonemia (DHS) has been implicated in the pathophysiology of ASD. Prior to its role as a neurotransmitter, serotonin functions as a developmental signal, promoting dendritic elaboration, synaptogenesis, cortical organization and autoregulation of the serotonergic system. Accordingly, it has been hypothesized that during the early stages of neural development, the diffusion of abnormally increased amounts of serotonin into the central nervous system, could induce changes in various neural networks relevant to ASD.

In the present study, rat pups were exposed to high levels of the serotonergic agonist 5‐methyloxytryptamine both pre‐and postnatally. This exposure produced changes in the dendritic architecture and synaptic connectivity of neurons in the dentate nucleus of the cerebellum. We observed changes in dendritic branching morphology such that DHS groups presented with short reaching, elaborately branched segments, expressing significantly fewer dendritic spines compared with controls. These alterations may be implicated in the neuropathological and behavioral changes observed in ASD.
Early Life Microbiome, Obesity and Diabetes
Authors: Blaser Martin
Published: June 2021

The congruence of the phylogenies of hominid hosts and their fecal microbiota provide strong evidence for vertical microbiota transmission extending for millions of years. Increasing evidence indicates that the vertically transmitted early life microbiota in mammals is involved in the choreography of host metabolic and immune development. We have used mouse models to assess microbiota roles in development, using perturbation by antibiotics as an experimental tool. Compared to untreated mice, we have found evidence for changes in microbiota diversity and community structure and metabolic activities, as well as changes in host intestinal and hepatic gene expression, immune cell populations, adiposity, and metabolic diseases. These murine models permit analysis of how antibiotic perturbations early in life predispose to obesity, metabolic syndrome, and diabetes in humans.
T Cell Receptor Recognition and the Composite Peptide/MHC Surface
Authors: Baker Brian
Published: June 2021

αβ T cell receptors (TCRs) recognize peptide antigens bound and “presented” by class I or class II major histocompatibility complex (MHC) proteins. Although the T cell‐mediated immune response is directed towards the antigenic peptide, the composite nature of the peptide/MHC ligand has substantial implications for TCR recognition. Here we describe how, at a structural and biophysical level, the common immunological distinction between peptide and MHC becomes blurred. This blurring extends to the TCR itself, such that widely‐held assumptions about the “roles” played by various TCR binding loops in antigen recognition cannot be easily supported. The more nuanced view of TCR recognition that emerges has implications for immunological specificity and cross‐reactivity, the development of the T cell repertoire, vaccine design, and efforts to engineer TCRs with therapeutic applicability.
Bioavailability of iron from plant and animal ferritins
Authors: lyu Chenyan , Lönnerdal Bo , zhao guanghua
Published: June 2021

Iron deficiency is a major public health problem in the world. Ferritin is being explored as a novel and natural strategy for iron supplementation. The objective of this study was to evaluate iron bioavailability from ferritin isolated from plant and animal sources. The stability of plant ferritin and animal ferritin and the effects of cooking and skim milk were studied by in vitro and in vivo digestion. Results from SDS‐PAGE and Western blot indicate that both plant ferritin and animal ferritin can resist digestion (both under acidic and moderately acidic conditions). Furthermore, ferritin was labelled with 59Fe and bioavailability of iron from ferritin was assessed by uptake into Caco‐2 cells. Our results indicate that iron is taken up from the ferritins and that iron bioavailability from soybean ferritin (rH‐1: rH‐2= 1:1) is the highest. These results may be explained by the binding of ferritin to Caco‐2 cells, which can be attributed to the interaction between ferritin and its putative receptor(s) at the surface of Caco‐2 cells. In conclusion, ferritin from plant and animal sources may be developed as an iron source.
Lower Prevalence Of Vitamin And Mineral Deficiencies Among Adolescent Users Of Full Spectrum Multivitamin/Multimineral Supplements
Authors: Murphy Rachel , Ciappio Eric , Bird Julia
Published: June 2021

Introduction

Adequate intake of vitamins and minerals is essential for supporting health, however intakes of several vitamins and minerals from food are below the recommendations in US adolescents. Dietary supplements (DS) and full spectrum multivitamin/multimineral (FSMV) supplements help improve nutrient intakes. We aimed to determine the prevalence of vitamin/mineral deficiency in US adolescents, and associations between DS and FSMV use and the prevalence of vitamin/mineral deficiency.

Methods

Cross‐sectional analysis of serum vitamins A, B6, B12, folate, C, D, E, and serum minerals iron and iodine in 4637 adolescents aged 9‐18y from the NHANES (2003‐2006) dataset. Deficiencies were defined using standard age and gender‐based cutoffs established by the CDC and the WHO. Supplement use categories were no DS use, DS use other than a FSMV, or use of a FSMV containing 蠅12 vitamins and 6‐14 minerals. Analyses took into account the complex survey design and were weighted to be representative of the US population.

Results

Overall, 26.4% of adolescents had at least 1 vitamin/mineral deficiency. 34.6% of females (14‐18y) were deficient in at least one nutrient. Among non‐DS users 23.3%, 4.98% and 1.21% were deficient in 1, 2, or 蠅3 vitamins/minerals. In comparison, the prevalence of deficiencies for DS and FSMV users was lower, with 18.3%, 2.31%, and 0.34% of DS users and 11.6%, 2.94% and 0.4% of FSMV users, respectively, having deficiencies in 1, 2, or 蠅3 vitamins/minerals. DS and FSMV users had a similar prevalence of vitamin/mineral deficiency, likely reflecting the small number of FSMV users.

Conclusion

Adolescent users of DS and FSMV have a lower prevalence of vitamin/mineral deficiencies compared to non‐users.
Examining the Influence of Cultural Immersion on Willingness to Try Fruits and Vegetables among Children in Guam: the Traditions study
Authors: Aflague Tanisha , Leon Guerrero Rachael , Boushey Carol
Published: June 2021

Culturally relevant programs among indigenous populations have had positive dietary outcomes, yet less is known about cultural immersion. This study examined the influence of cultural immersion on willingness to try fruits and vegetables (FV) among children 3‐12 y in Guam. A pre‐post, quasi‐experimental design was used to evaluate 3 summer camps with different exposure levels of cultural immersion. High, moderate, and zero exposure was provided by a cultural immersion camp (CIC), a university‐based day camp (UDC), and a recreational sports camp (RSC), respectively. CIC (n=47) delivered 4 culturally adapted nutrition lessons within the context of Chamorro cultural traditions. The UDC (n=23) delivered the same lessons within a physiology framework. The RSC (n=33) was without nutrition lessons and cultural immersion. Children's willingness to try FV was assessed with the interview‐administered WillTry tool before (± 2 weeks) and after (± 1 week) each summer program. Outcomes examined WillTry post‐scores using multivariate regression models adjusting for the relevant pre‐score, sex, age, ethnicity, dose, BMI, and parent's cultural affiliation. Post‐WillTry scores for local novel FV by highest exposure camp to lowest were 2.30, 2.33, 2.27. For local common FV, the post‐scores were 2.62, 2.61, 2.56, respectively. No differences by the primary outcomes were found. An unexpected result was the higher imported FV WillTry post‐score of 2.81 for RSC compared to the 2.75 for UDC (P=0.023). The Traditions study is the first to explore novel influences on dietary habits and reveals further research involving indigenous peoples and cultural immersion are needed.
Cardiometabolic and Immunological Impacts of Extra Virgin Olive Oil Consumption in Overweight and Obese Older Adults: A Randomized Controlled Trial
Authors: Rozati Mitra , Barnett Junaidah , Wu Dayong , Handelman Garry , Dallal Gerard , Saltzman Edward , Wilson Thomas , Li Lijun , Wang Junpeng , Marcos Ascensión , Ordovás José , Lee Yu‐Chi , Meydani Mohsen , Meydani Simin
Published: June 2021

Both aging and obesity are related to dysregulated immune function and increased risk of infection and chronic non‐infectious diseases. Dietary lipids are known to impact immune responses and cardiometabolic risk factors. We determined effect of replacing oils used in a typical American diet with extra virgin olive oil (EVOO) for 3 mo on immune and inflammatory responses and cardiometabolic risk factors in overweight and obese older adults. Forty‐one participants (aged 蠅65) who consumed a typical American diet were randomized into the control (CON, n=21) group to consume a mixture of corn, soybean oil and butter, and the olive oil (OO, n=20) group to consume EVOO to replace substitutable oils in their diet. At baseline and 3 mo, we measured cardiometabolic, and in vivo and ex vivo immunologic parameters. Compared to the CON group, the OO group showed decreased systolic blood pressure (P < 0.05), a strong trend toward increased plasma HDL‐C concentrations (P = 0.06), and increased T cell proliferative response (P < 0.05). No differences were found in T cell phenotype, cytokine production, and delayed‐type hypersensitivity skin response between the two groups. Our results indicate that substitution of oils used in a typical American diet with EVOO in overweight and obese older adults may have cardiometabolic and immunological health benefits.
Investigation of the 3‐epimer of 25‐hydroxyvitamin D3 in urban schoolchildren
Authors: Berger Samantha , Van Rompay Maria , Gordon Catherine , Goodman Elizabeth , Economos Christina , Eliasziw Misha , Holick Michael , Sacheck Jennifer
Published: June 2021

Objective

The biological relevance of the 3‐epimer of 25‐hydroxyvitamin D (25OHD) is not well classified. Our goal was to examine associations between serum 3‐epimer and demographics and blood lipids in diverse school‐aged children.

Methods

Multivariate logistic and linear regression models were used to examine relationships between having detectable 3‐epimer, demographics and blood lipids, controlling for age, sex, race, puberty status, BMI z‐score and total 25OHD, in Boston‐area urban schoolchildren (n=687, 8‐15 yrs).

Results

40% exhibited total 25OHD <20ng/mL and 49% had detectable 3‐epimer. Serum 3‐epimer was correlated with total 25OHD (r=0.36). Being female (OR 0.69, 95%CI: 0.49‐0.96) and race (Asian vs. white, OR 0.24, 95%CI: 0.11‐0.50) were associated with a lower likelihood of having detectable 3‐epimer. Significant interactions between detectable 3‐epimer and sex and puberty status revealed that females with detectable 3‐epimer had higher HDL cholesterol (3.0 mg/dL, p=0.03) and triglycerides (0.90 mg/dL, p=0.02) while pre‐pubertal children with detectable 3‐epimer had higher triglycerides (0.99 mg/dL, p=0.02).

Conclusion

This study provides insight into prevalence of detectable 3‐epimer levels in children and variation in the relationship between detectable 3‐epimer and blood lipids by sex and puberty status.
Vitamin D Supplementation and Quality of Life Following Diagnosis in Stage II Colorectal Cancer Survivors
Authors: Lewis Cari , Xun Pengcheng , He Ka
Published: June 2021

Research shows people are motivated to change their lifestyles following a cancer diagnosis; however few studies have investigated whether these changes could benefit people's health condition. The objective of this study was to examine the associations between vitamin D supplementation and quality of life (QoL) in stage II colorectal cancer (CRC) patients after diagnosis. A total of 453 newly diagnosed patients were enrolled in the North Carolina Central Cancer Registry from 2009 to 2011. Data on demographic and lifestyle variables, treatment, diet and supplementation were collected at diagnosis, 12‐, and 24 months post‐diagnosis. QoL was measured via the Functional Assessment of Cancer Therapy‐Colorectal Cancer (FACT‐C) and the 12‐item Short Form survey of medical outcomes (SF‐12). After adjustment for potential confounders, a positive association was found between baseline vitamin D supplementation (yes vs.no) and the CRC subscale of the FACT‐C (β = 1.28; 95% CI: 0.07 – 2.48). A positive trend between vitamin D change and changes in Functional wellbeing scale was also found, which remained in those who did not decrease calcium supplementation, but not in those increased (Pinteraction<0.01). An increase in vitamin D consumption was also positively associated with change in the physical component score of the SF‐12 (β = 2.98; 0.37 – 5.60) over 2 years. No association was found with risk of reoccurrence or mortality. This study suggests that changes in supplementation may influence QoL following diagnosis in stage II CRC survivors. Future research should address the dose‐response relationship of interest. This work was supported by the American Cancer Society (RSGT‐08‐094‐CPPB).
Alternate‐day fasting and daily calorie restriction similarly affect visceral adiposity and circulating inflammatory cytokine concentrations
Authors: Trepanowski John , Kroeger Cynthia , Barnosky Adrienne , Hoddy Kristin , Varady Krista
Published: June 2021

Background

Visceral obesity is associated with dysregulated inflammatory cytokine secretion. We tested the hypothesis that alternate‐day fasting (ADF) would preferentially reduce visceral fat mass and normalize circulating inflammatory cytokines compared to daily calorie restriction (CR).

Methods

Overweight and obese subjects (n = 62) were randomized to 1 of 3 groups for 24 weeks: 1) ADF (feed day: 125% of energy needs, alternated with a fast day: 25% of energy needs; all meals provided); 2) CR (75% of energy needs every day; all meals provided); 3) Control (100% of energy needs every day; self‐selected diet).

Results

Changes in visceral fat mass and concentrations of all measured circulating inflammatory cytokines were similar among all three groups (p > 0.05 for all comparisons). After pooling together the data from the dietary intervention groups, C‐reactive protein decreased relative to the control group (0.19 mg/dl; p < 0.02), while insulin‐like growth factor 1 decreased in the control group relative to the dietary intervention groups (24 ng/ml; p < 0.03). There were no changes between the dietary intervention groups and the control group for tumor necrosis factor α, interleukin 6, adiponectin, leptin, or resistin (p > 0.05 for all comparisons).

Conclusion

ADF and CR produce similar changes in C‐reactive protein and insulin‐like growth factor‐1 relative to a control group.
The Metabolic Response to a Standardized High Fat, High Calorie Meal in Healthy Obese Individuals is Similar to that of Healthy Lean Individuals
Authors: Mutch David , Lam Karen , Britz‐McKibbin Philip , Badoud Flavia
Published: June 2021

Obesity is associated with numerous health complications; however, a subgroup of individuals (termed the metabolically healthy obese or MHO) may be protected from the cardiometabolic complications typically associated with a high body mass index. We previously showed that MHO individuals have reduced levels of serum inflammatory markers and saturated fatty acids (FAs), as well as altered adipose tissue amino acid homeostasis, compared to their metabolically unhealthy obese (MUO) counterparts. Building on this past foundational work, the goal of this study was to examine the postprandial metabolic response to a standardized high fat, high calorie meal in lean healthy (LH), MHO, and MUO individuals. Blood glucose and insulin levels were measured during the 2 h postprandial period and used to calculate the area under the curve (AUC). The AUC for both glucose and insulin were similar between LH and MHO individuals, and significantly lower compared to MUO individuals (p<0.05). Gas chromatography and capillary electrophoresis‐mass spectrometry revealed significant postprandial differences in several FAs and amino acids, respectively, between MHO and MUO individuals. Furthermore, we found that baseline levels of various FAs and amino acids were predictive of the glycemic and insulinemic postprandial response. Taken together, our results highlight that MHO individuals represent an important subgroup of obesity that appear to have a preserved metabolic response to a challenge meal in comparison to their MUO counterparts.

Grant Funding Source: Supported by CIHR
APotato (Poly)phenols on Postprandial Insulinemia and Platelet Aggregation in Premenopausal Overweight Women: A Pilot Study
Authors: Huang Yancui , Qian Cheng , Xiao Di , Rudraiah Laasya , Park Eunyoung , Edirisinghe Indika , Burton‐Freeman Britt
Published: June 2021

Potatoes are known for their carbohydrate, potassium, vitamin C and fiber content; however potatoes also contain chlorogenic acids (CGA). Colored potatoes may contain additional (poly)phenols, such as anthocyanins (ACN) in purple potatoes. Polyphenols exert various health promoting biological effects. Previous work suggests CGA and ACN have a role in glycemic control and platelet function. The present study examined two potato varieties: white potato (WP) containing CGA and purple potato (PP) containing CGA and ACN in a 6 h postprandial study in women (n=12, crossover design) on postprandial metabolic and epinephrine (EPI)‐ and ADP‐ induced platelet aggregation responses. Potatoes (200 g cooked) were included in a high carbohydrate, high fat breakfast (~690 kcal). A demographically match control group (CON, n=8) consumed a rice substituted breakfast without CGA or ACN and were used for metabolic comparisons only. PP and WP significantly reduced postprandial insulin responses compared to CON (p<0.05). Glucose responses were not different among groups. PP significantly inhibited EPI‐induced‐ (p=0.015) and ADP‐induced‐ (P=0.009) platelet aggregation compared to WP. Potatoes compared to a common starch replacement reduced the insulin demand to achieve post‐meal glucose homeostasis. PP with CGA and ACN prolonged platelet aggregation time compared to WP, suggesting a potential role for certain potato varieties containing (poly)phenols in cardiovascular disease risk reduction. The work supports future research to explore potatoes and cardio‐metabolic health.

Supported by various donor funds.
The Effect of Vitamin D Supplementation on Glucose Homeostasis among African Americans and Hispanics with Type 2 Diabetes
Authors: Exebio Joel , Zarini Gustavo , Vaccaro Joan , Ajabshir Sahar , Huffman Fatma
Published: June 2021

The aim of the present study is to determine the effect of supplemental vitamin D intake (4000 IU or 6000 IU of cholecalciferol daily for 6 months) on fasting plasma glucose, fasting insulin, and glycosylated hemoglobin (A1C) in a sample of African Americans and Hispanics with type 2 diabetes and vitamin D insufficiency. Seventy five participants were recruited by community outreach. Plasma glucose concentration was measured by hexokinase enzymatic method. A1C was measured by the DCA2000+ system. Insulin in fasting blood was determined by radioimmunoassay. Serum vitamin D concentrations were measured with an enzyme‐immunoassay kit. General lineal model was used to compare treatment effects and Bonferroni multiple comparison tests was used to detect significant changes from baseline, 3 months, and 6 months on the outcome variables. No significant changes were observed for fasting plasma glucose, insulin or A1C between groups and within groups. Vitamin D supplementation did not improve glucose homeostasis in this sample. Funding for this research was provided through an NIH/NIDDK sponsored grant.
Dietary Patterns and Risk of Age‐Related Macular Degeneration After More Than Two Decades of Follow‐Up
Authors: Wu Juan , Schaumberg Debra , Fung Teresa , Sastry Srinivas , Willett Walter
Published: June 2021

Method

This prospective study included 76,693 female participants in the Nurses' Health Study and 39,519 male participants in the Health Professionals Follow‐Up Study. We developed two cardioprotective dietary patterns, the Dietary Approaches to Stop Hypertension (DASH) and the alternative Mediterranean Diet (aMED), and two overall dietary patterns from factor analysis, prudent and western pattern. We calculated each dietary pattern score from repeated food frequency questionnaires. We confirmed 1,531 intermediate and 1,269 advanced age‐related macular degeneration (AMD) cases. Cox proportional hazards model was used to estimate the relative risks (RR's) and 95% confidence intervals (CI's).

Results

For advanced AMD, the prudent dietary pattern was inversely associated with risk (comparing extreme quintiles, multivariate RR = 0.77, 95% CI = 0.63 to 0.94; p trend = 0.008), whereas the western pattern was positively related to risk (RR = 1.36; 95% CI = 1.09 to 1.71; p trend = 0.005). The RR for DASH was 0.83 (95% CI = 0.69 to 1.00; p trend = 0.01) and for aMED was 0.86 (95% CI = 0.71 to 1.04; p trend = 0.10). In contrast, none of the dietary patterns was associated with intermediate AMD.

Conclusion

DASH diet protects against advanced AMD, likely reflecting shared risk factors between cardiovascular disease and AMD. However, broadly, a prudent dietary pattern with a high intake of plant‐based foods may reduce the risk of advanced AMD whereas a western pattern with a high intake of red meat, butter, and refined grains may increase the risk.
Household Food Insecurity and Asthma in the 3rd Grade of the Early Childhood Longitudinal Study‐Kindergarten Cohort
Authors: Mangini L , Dong Y , Hayward M , Forman M
Published: June 2021

In 2013, 20% of U.S. households with children experienced food insecurity, which is associated with poor physical and nutritional health and shares determinants such as poverty and race with asthma. Asthma afflicts over 7 million American children, and prevalence rates have steadily increased while incidence peaks in young children. Asthma is positively associated with childhood obesity; however, limited research on the relationship between food insecurity and asthma exists. The objective was to determine the association between food insecurity and asthma in a diverse sample of 3rd graders.
Cross‐sectional data from the 3rd grade year (2002) of the Early Childhood Longitudinal Study‐ Kindergarten cohort (ECLS‐K) were analyzed (N=11,480). Food security status was measured with the 18‐item USDA module. Asthma diagnosis and sociodemographic characteristics were based on parental report; anthropometric data were collected in person. Multivariate logistic regression was done to test the association between food security status and asthma, controlling for covariates.
Children in food‐insecure households had higher odds of asthma (OR 1.38, 95% CI 1.12‐1.70), independent of sex, race, weight, insurance coverage, household poverty, or maternal nativity or education. Being male (OR 1.82, 95% CI 1.62‐2.05), non‐Hispanic Black (OR 1.77, 95% CI 1.49‐2.09) or Hispanic (OR 1.36, 95% CI 1.13‐1.64), and/or overweight (OR 1.25, 95% CI 1.06‐1.46) or obese (OR 1.63, 95% CI 1.42‐1.87) were positively associated with asthma.

Food insecurity represents a threat to children's health beyond sociodemographic factors. Interventions to reduce chronic disease outcomes may need to address food insecurity.
Health Care Costs Associated with Household Food Insecurity in Ontario, Canada
Authors: Tarasuk Valerie , Gundersen Craig , Cheng Joyce , DeOliveira Claire , Dachner Naomi
Published: June 2021

A broad spectrum of health conditions has been linked to household food insecurity in Canada and the US, but the health care costs associated with food insecurity have not been well documented. We examined the relationship between individuals' household food security status over a 12‐month period and their health care utilization and resultant costs during this period, using data for 67,033 Ontario adults 18‐64 yr from the Canadian Community Health Survey for 2005 and 2007‐2010 linked with administrative health care data from Ontario. Two‐part regression analyses were conducted, adjusting for age, sex, education, home ownership, household composition, and neighborhood income quintile. Based on responses to the Household Food Security Survey Module, 12% of the sample was food insecure (4% marginal, 5% moderate and 3% severe). Over the 12 months, 89% used some health care, with odds of utilization 1.71 times higher (95% CI: 1.44, 2.04) for adults in severely food insecure households compared to fully food secure households. Among health care users, total health care costs rose significantly with food insecurity, increasing by 15% with marginal insecurity, 27% with moderate insecurity, and 56% with severe insecurity, when compared to the food secure. Our results suggest that household food security status is a robust predictor of health care costs, independent of other social determinants of health, and that food insecurity contributes significantly to health care expenditures in Ontario. Funded by the Canadian Institutes of Health Research (FRN 115208).
Low and Very Low Food Security are Associated with Differences in Emotional and Behavioral Problems among Children and Adolescents in the US
Authors: Burke Michael , Martini Lauren , Cayir Ebru , Hartline‐Grafton Heather , Meade Randa
Published: June 2021

The adverse association between food insecurity and emotional and behavioral problems (EBP) among children and adolescents has been studied, but little work has examined if more severe food insecurity is associated with higher EBP.

Using a national sample of households (HH) with children and adolescents, we examined the association between EBP and food security status (FSS) (i.e., food secure (FS), low food secure (LFS), and very low food secure (VLFS)). Data were collected from a total of 22,522 children and adolescents from 2011 to 2013.

The Strengths and Difficulties Questionnaire (SDQ) and the 10‐item USDA HH Food Security Survey were used to measure EBP and FSS. Negative binomial and logistic regressions were used to test the associations between total SDQ score, high SDQ score (SDQ score 蠅 6), and FSS. All models adjusted for demographic and socioeconomic confounders.

Compared to FS HH, children and adolescents in LFS or VLFS HH had higher SDQ scores (LFS, incidence rate ratio (IRR) 1.22, p<0.001; VLFS IRR 1.37, p<0.001) and had increased odds of having a high SDQ score (LFS, odds ratio (OR) 1.35, p<0.05; VLFS OR 2.07, p<0.001). Compared to LFS HH, VLFS HH had a mean IRR that was 0.12 higher (p<0.01) and a mean OR that was 0.43 higher (p<0.01).

Compared to LFS HH, children and adolescent in VLFS HH have higher EBP. In addition, compared to FS HH, children and adolescents in LFS and VLFS have higher EBP. This work was supported by FRAC.
Components of a Mediterranean Diet are Associated with Gut Permeability in Obese Adults
Authors: Moss Olivia , Keshavarzian Ali , Tangney Christy , Shawron Krista , Kester Kelly , Clifford Kerry , Piazza Bryana , Shaikh Maliha , Betz Melanie , Rasmussen Heather
Published: June 2021

Increased gut permeability allows translocation of inflammatory microbiota products into the host system. However, it is unknown how dietary patterns and their components impact permeability. Therefore, the objective was to determine if a Mediterranean dietary (MedDiet) pattern is associated with gut permeability. In this cross‐sectional study, urine was collected after a sugar challenge (mannitol, sucrose, sucralose, lactulose) in 32 obese (BMI, mean ± SD; 37.0 ± 6.0 kg/m2) adults aged 47.0 ± 10.9 yrs; 59% were African American and 81% were female. Collections at the 5‐ and 24‐hr time points were analyzed. All completed a 16‐component MedDiet screener. Median (IQR) overall MedDiet score was 8 (6, 9). There were no differences in permeability (% oral sugar dose excreted; Mann Whitney U) observed between those assessed as MedDiet accordant (蠅 8) vs those not accordant. Those accordant to the green leafy vegetable, berries, red meat, chicken, beans, sweets, and fast‐food subcomponents had lower permeability than those not accordant; most notably, gastro‐duodenal (5‐hr sucrose; 0.22 [0.14, 0.75] vs 0.42 [0.25, 0.73]), small bowel (5‐hr lactulose; 0.56 [0.31, 0.75] vs 0.84 [0.61, 1.4]), and total gut permeability (24‐hr sucralose; 0.37 [0.21, 1.00] vs 0.86 [0.54, 1.82]) was lower in those accordant vs those not accordant to the berries subcomponent. Accordance to the fast‐food subcomponent had lower total gut permeability, with greater than a two‐fold difference in 24‐hr sucralose:lactulose between accordance and non‐accordance (0.16 [0.08, 0.36] vs 0.40 [0.24, 0.57]). While exploratory, these data suggest that specific subcomponents of a MedDiet may be protective to the intestinal barrier.