bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered Islet Function May Promote a Lean Phenotype in Tafazzin Deficient Mice
Authors: Cole Laura Kathleen , Doucette Christine , Vandel Marilyne , Fonseca Mario , Xiang Bo , Dolinsky Vernon Wayne , Hatch Grant Michael
Published: November 2023

Tafazzin is a transacylase that maintains mitochondrial membrane integrity and the function of the mitochondrial respiratory chain. Specifically, tafazzin maintains the content and molecular structure of the unique tetra‐acyl phospholipid cardiolipin (CL) located in the inner mitochondrial membrane. Despite abundant evidence that mitochondrial dysfunction is associated with insulin resistance, little is known about the potential role of CL and tafazzin in the trajectory of this disease. To investigate the in vivo effects of tafazzin deficiency, we have utilized a mouse model with a doxycycline‐ inducible tafazzin shRNA knock‐down. We have previously established that tafazzin knock‐down mice are protected against the development of obesity, and insulin resistance compared to control litter mates. Tafazzin deficiency promotes a lean phenotype due to a coordinated elevation in adipose lipolysis and hepatic fatty acid oxidation. We have now determined that glucagon and insulin levels in the blood and whole islets are significantly reduced with tafazzin deficiency. We have also ascertained that the quantity and function of beta‐cells were similar between genotypes. However, despite similar levels of alpha‐cells, glucagon secretion during high‐glucose conditions was elevated from islets isolated from tafazzin knock‐down mice. As a result, tafazzin knock‐down mice exhibited significantly higher circulating ratios of glucagon to insulin during glucose challenges. Our experiments indicate that tafazzin may have a role in regulating islet function. These data also suggest that mice deficient in tafazzin may be protected in part against weight gain by promoting glucagon secretion during fed states. Since, the development of type 2 diabetes is closely related to obesity and pancreatic function altering cardiolipin synthesis may be a novel therapeutic option for patients at risk for type 2 diabetes.

Support or Funding Information

Heart and Stroke Foundation of Canada

Children's Hospital Research Institute of Manitoba
Investigation of Free Fatty Acid on Concerted Trafficking of KATP and Kv2.1 Channels in the Adipoinsular Axis in vivo and in vitro
Authors: Ruan Jing‐Syuan , Chen Pei‐Chun
Published: November 2023

Type 2 diabetes is the most prevalent metabolic syndrome worldwide and obesity is the major risk factor. The high level of fatty acid accumulation can be observed in the pancreatic β‐cells so called lipotoxicity. The overload of free fatty acid contributes to pancreatic β‐cells apoptosis and dysfunction that are associated with the disease progression. Insulin and leptin form as the adipoinsular axis, a dual regulatory loop maintains nutrient balance. High blood glucose triggers insulin release in pancreatic β‐cells and insulin further stimulates leptin release from adipocytes. Leptin can directly act on pancreatic β‐cells to suppress insulin secretion. Plasma leptin concentration is proportional to body fat mass so it's not surprising that high plasma leptin can be observed in obese individuals. Unfortunately, leptin resistance is easily to develop therefore, chronic leptin treatment is not an effective way to treat obesity. ATP‐sensitive potassium channels (KATP channels) are essential to the connection between membrane excitability and glucose‐stimulated insulin secretion (GSIS). Physiologic role of KATP channels depend on the correct trafficking and cell surface expression. Based on the previous publication, leptin signaling leads to simultaneous increase surface expression of KATP and Kv2.1 channels that is dependent on AMPK, PKA as well as actin depolymerization and this action would cause membrane potential hyperpolarization to reduce insulin secretion. The goal of this study is to understand the effect of fatty acid on trafficking of KATP and Kv2.1 channels in adipoinsular axis. We hypothesize that free fatty acid would induce the change of membrane potentials that results in the defect of KATP and Kv2.1 channels trafficking and this would cause cell malfunction and lead to cell death in obesity‐induced type 2 diabetic β‐cells. The following three specific aims are proposed to comprehensively investigate the above hypothesis: Aim 1: to evaluate the effect of free fatty acid on the adipoinsular axis in vivo using molecular genetic approaches as well as electrophysiological experiments. Aim 2: to understand if concerted trafficking of KATP and Kv2.1 channels plays a role in free fatty acid induced apoptosis using pharmacological approaches. Aim 3: to manipulate whether concerted trafficking of KATP and Kv2.1 channels can recover the adipoinsular axis and enhance cell viability using type 2 diabetes animal model, including diet induced obese mice and leptin receptor knockout mice (db/db). The study provides the new insight by manipulating KATP and Kv2.1 channels trafficking to overcome metabolic diseases related to unbalanced adipoinsular axis.

Support or Funding Information

This work are supported by MoST grants (103‐2320‐B‐006‐005‐MY2 and 105‐2628‐B‐006‐MY3) to P‐C Chen.
Adiponectin receptor 1 resists the decline of serum osteocalcin and GPRC6A expression in ovariectomized mice
Authors: Lin YuanYu , Chen ChingYi , Wu Shinn Chih , Ding ShihTorng
Published: November 2023

Hormonal changes that cause metabolic complications are a common problem in postmenopausal women. Adiponectin and osteocalcin are cytokines associated with glucose regulatory and insulin sensitized function in postmenopausal stages. The current study investigated the role of adiponectin signaling and osteocalcin mediated function in glucose metabolism in ovariectomized mice. In a mouse menopausal‐related metabolic disorder model, overexpression of adiponectin receptor 1 improved glucose tolerance and caused resistance to body weight increase and decline of serum osteocalcin. Furthermore, adiponectin receptor 1 transgenic ovariectomized mice had higher GPRC6A (the putative osteocalcin receptor) expression in muscle tissue. Immunofluorescence indicated that GPRC6A and adiponectin receptor 1 were co‐localized in mouse muscle tissues. The present finding suggested adiponectin receptor 1 can mediate the improvement of glucose metabolism by osteocalcin in ovariectomized mice. Our findings imply the possibility to ameliorate menopause‐induced metabolic disorder by GPRC6A and adiponectin signaling.

Support or Funding Information

This study was supported in part by the Grants NSC 102‐2313‐B‐002‐026‐MY3 and NSC 99‐2628‐B‐002‐067‐MY3 grants from Ministry of Science and Technology in Taiwan.
Use of a three dimensional porcine retinal explant model to detect HIF1α for understanding diabetic retinopathy
Authors: Iwuagwu B. U. , Cruickshank S. F. , Rowe I. , Knott R. M.
Published: November 2023

Introduction

Diabetic retinopathy is a major microvascular complication of diabetes mellitus and a leading cause of blindness [1]. Hypoxia is suggested to play a crucial pathophysiological role in diabetic retinopathy (DR) [2], but the exact mechanisms are complex and the precise events are still debated. An agarose‐collagen three‐dimensional (3D) porcine retinal explant model is used here to investigate the expression of the hypoxia inducible factor ‐1 alpha (HIF‐1α), a transcription factor critical for cellular response to hypoxia [2].

Aim

To study the expression and localization of the hypoxia‐inducible factor 1 alpha ((HIF)‐1α, a key target in DR using a 3D porcine retinal explant model.

Method

Porcine retinal tissues were extracted from ocular globes, (n ≥ 6) donated by a local abattoir. Extracts were cultured in DMEM within a 3D matrix derived from 0.5% agarose + collagen (0.25mg/ml) co‐gel solution and explants were maintained in a humidified atmosphere with 5% CO2 at 37°C. Explants were harvested at less than 2 h (T0) and 24 h (T1) post culture, fixed overnight in 10% neutral buffered formalin (NBF) and incubated in 30% sucrose. Serial sections (20μm) were cut using a cryostat. To ascertain tissue integrity, sections were stained with Mayer's hematoxylin and Eosin according to protocol (Sigma‐Aldrich). To detect the expression and sub‐cellular location of the hypoxia inducible factor (HIF) 1α at T0 and T1, sections (20μm) were washed 2 × 15 minutes in 50mM Tris buffered saline (TBS) plus 0.1% Triton X‐100, followed with blocking in 10% normal goat serum/1% bovine serum albumin (BSA) (Santa Cruz) for 2 hours at room temperature with final incubation with primary mouse anti‐Hif1α (Thermo Fischer) (1:20) overnight at 4°C. Post‐incubation, specimens were rinsed 1 × 15 minutes with TBS 0.1% Triton. Non‐specific endogenous peroxidase reaction was blocked with 0.3% H2O2 in 0.3% normal serum (goat) in TBS for 15 minutes at RT. Goat anti‐Mouse IgG (H+L) secondary antibody, DyLight 488 (Thermo Fischer scientific) (1:200) was used for detection.

Results & Conclusion

H & E stain demonstrated preservation of retinal integrity and does indicate that the use of agarose‐based 3D system provided structural and mechanical support which may have prevented early retinal tissue degeneration. Preliminary immunohistochemistry results revealed positive identification of HIF1α expression at less than 2 h (T0) and 24 h (T1). HIF1‐α expression was localized in the photoreceptor and dispersed throughout the outer and inner layers of the retina. Further investigation is needed to establish the precise cell‐specific co‐localization of HIF1α.

Support or Funding Information

Benedicta Iwuagwu, the presenting author is a recipient of an academic scholarship from the Robert Gordon University (RGU). This thesis is fully funded by RGU and the author receives a tax‐free monthly personal stipend in addition from the university.
Potential role of hepatic lipase in the accrual of docosahexaenoic acid (DHA) in the brain
Authors: Dhavamani Sugasini , Yang Peng , Ng Dominic , Khetarpal Sumeet , Vitali Cecilia , Rader Daniel , Subbaiah Papasani
Published: November 2023

DHA is an essential fatty acid that is required for the normal development and function of the brain. Because of its inability to synthesize adequate amounts of DHA from the precursors, the brain has to acquire DHA through the blood brain barrier (BBB). Recent studies demonstrated the presence of a transporter at the BBB that specifically transports DHA into the brain in the form of lysophosphatidylcholine (LPC‐DHA). However, the mechanism by which LPC‐DHA is generated in the plasma is not known. Our previous studies showed that there are three different enzymes in plasma‐ lecithin cholesterol acyltransferase (LCAT), endothelial lipase (EL), and hepatic lipase (HL), which can generate LPC‐DHA from sn‐2 DHA PC of lipoproteins. In this study we determined the potential roles of these enzymes in the delivery of DHA to the brain by examining the brain DHA levels in the mice genetically deficient in each of these enzymes. The results show that the brain DHA levels of LCAT‐deficient mice (16.3%) or EL‐deficient mice (15.2%) were not significantly lower than those of their littermates. However, the concentration of brain DHA was significantly lower in HL knockout (KO) mice (13.5%) compared to their littermates (17.1%) (p<0.002). The DHA levels were also lower in the plasma but not in the liver, or heart of HL KO mice. Furthermore, the concentration of LPC‐DHA was significantly decreased in the plasma of HL KO mice. These results suggest that HL may be important for the supply of DHA to the brain by generating LPC‐DHA either in the plasma itself, or in the liver, followed by its secretion into plasma.

Support or Funding Information

Supported by NIH R01 HL 68685 (PVS)
Crystal structure and activation mechanism of human neutral sphingomyelinase 2
Authors: Shanbhogue Prajna , Airola Michael , Shamseddine Achraf , Guja Kip , Maini Rohan , Bartke Nana , Wu Bill , Obeid Lina , Garcia‐Diaz Miguel , Hannun Yusuf
Published: November 2023

Neutral sphingomyelinase 2 (nSMase2) is a magnesium‐dependent phophodiesterase that generates the bioactive sphingolipid ceramide. Ceramide is a critically important secondary messenger that acts in a variety of cellular pathways such as apoptosis, inflammation, cell growth and differentiation. Accordingly, mutations in nSMase2 can affect ceramide production and have been implicated in cancers of the breast, urinary bladder and colon. Obtaining a detailed understanding of the structure and function of this enzyme is of significant interest and has the potential to uncover new avenues for cancer therapeutics. We have obtained the first high‐resolution X‐ray crystallographic structure of human nSMase2 and developed a yeast two‐hybrid system to analyze its inter‐domain interactions, which likely play a role in activation of the enzyme by anionic phospholipids (APLs). Previous work in our laboratory identified amino acid residues in the N‐terminal hydrophobic domain of nSMase2 that interact with APLs in the inner membrane. Our current results suggest that these residues also interact with the cytoplasmic C‐terminal domain of nSMase2 and may help regulate activation of the enzyme by APLs. Furthermore, we have identified additional amino acid residues in the juxtamembrane region of nSMase2 that may also contribute to regulation of enzyme activity. In sum, our results provide a model for activation of nSMase2, and reveal a novel structure that paves the way for rational drug design endeavors.

Support or Funding Information

This work was supported by grants from the National Institutes of Health R37GM043825 (to Y.A.H.), R01GM100021 (to M.G.D.), F32GM100679 (to M.V.A.), and F30ES022930 (to K.E.G.).
Phosphorylation of the Nem1‐Spo7/Pah1 Phosphatase Cascade by Pkc1 Protein Kinase C
Authors: Dey Prabuddha , Su Wen‐Min , Carman George M
Published: November 2023

In the yeast Saccharomyces cerevisiae, the Pah1 phosphatidate phosphatase is responsible for catalyzing the penultimate step in the synthesis of triacylglycerol. Phosphatidate phosphatase dephosphorylates phosphatidate to form diacylglycerol, the precursor of triacylglycerol. Pah1 exists in the cytosol as a phosphoprotein, but it must be dephosphorylated by the Nem1‐Spo7 protein phosphatase for its interaction with the ER membrane to associate with the substrate phosphatidate. In this work, we examined the regulation of the Nem1‐Spo7/Pah1 phosphatase cascade by its phosphorylation by Pkc1 protein kinase C (PKC). Pah1, Nem1, and Spo7 were expressed and purified from Escherichia coli to utilize non‐phosphorylated pristine substrates for PKC, which was purified from yeast. PKC phosphorylated each component of the phosphatase cascade on a serine residue, and the reactions were dependent on phosphatidylserine (0.5 mM) and diacylglycerol (0.15 mM) for the maximum phosphorylations. This was a surprising result given the fact that previous data indicated that yeast PKC does not require lipids for its activity, at least in the absence of GTP‐bound Rho1. Owing that prior work on yeast PKC utilized a peptide substrate, we examined the PKC activity using peptide substrates with sequences derived from Nem1, Spo7, or Pah1. With these substrates, PKC did not require phosphatidylserine and/or diacylglycerol for its activity. We found that mammalian PKC, using Pah1 or the Pah1‐derived peptide as substrates, were dependent on phosphatidylserine and diacylglycerol for activity. These results indicated a fundamental difference in the mechanisms of the reactions catalyzed by the yeast and mammalian PKC enzymes, and that yeast PKC is likely to require lipids for activity in vivo.

Support or Funding Information

Supported by NIH grant GM050679
ANGPTL8 Promotes the Ability of ANGPTL3 to Inhibit Lipoprotein Lipase
Authors: Davies Brandon S.J. , Chi Xun , Britt Emily C. , Shows Hannah W. , Hjelmaas Alexander J. , Shetty Shwetha K. , Cushing Emily M. , Zhang Ren
Published: November 2023

Lipoprotein lipase (LPL) is critically important for the delivery of plasma lipoprotein–derived triglycerides to peripheral tissues. Activity of LPL is carefully regulated and misregulation of LPL can contribute to metabolic diseases including obesity, metabolic syndrome, and cardiovascular disease. Several members of the angiopoietin‐like (ANGPTL) family of proteins, including ANGPTL3 and ANGPTL8, regulate LPL activity. Deficiency in either ANGPTL3 or ANGPTL8 reduces plasma triglyceride levels and increases LPL activity, whereas overexpression of either protein does the opposite. Recent studies showed that ANGPTL8 overexpression only raises plasma triglycerides when ANGPTL3 is present suggesting that ANGPTL3 and ANGPTL8 work together to alter clearance of plasma triglycerides, however the nature of this interaction has remained elusive. We tested the hypothesis that ANGPTL8 forms a complex with ANGPTL3 and that this complex is necessary for efficient inhibition of LPL. We found that ANGPTL3 or ANGPTL8 alone could inhibit LPL only at concentrations that far exceeded physiological levels, especially when LPL was bound to its endothelial cell receptor/transporter GPIHBP1 (glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1). Physical interaction was observed between ANGPTL3 and ANGPTL8 when the proteins were co‐expressed, and co‐expression with ANGPTL3 greatly enhanced the secretion of ANGPTL8. Importantly, the ability of ANGPTL3‐ANGPTL8 complexes to inhibit LPL was dramatically increased compared to either protein alone. Part of this improvement could be ascribed to an improved ability to bind LPL as protein interaction assays showed that ANGPTL8 increased the ability of ANGPTL3 to bind LPL. Together, these data suggest that ANGPTL8 binds to ANGPTL3, forming a complex that has an increased ability to bind and inhibit LPL.

Support or Funding Information

This work was supported by grants from the NHLBI (HL130146) and the Carver Medical Research Initiative
Microbiota‐sensing O‐GlcNAc signaling in intestinal and metabolic homeostasis
Authors: Ruan Hai‐Bin , Zhao Ming
Published: November 2023

The gut microbiota plays a fundamental role for host metabolism and immune response. Alterations in microbial composition and function have been associated with many diseases, including obesity, diabetes, inflammatory bowel disease, and liver diseases. Microbial metabolism yields a number of bioactive molecules such as short‐chain fatty acids (SCFAs) that may modulate host physiology; however, the molecular mechanisms by which host cells sense and respond to microbiota‐derived molecules are largely unknown.

O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) signaling has been proposed as a nutrient sensor in diverse metabolic processes. Herein, we investigated the role of O‐GlcNAc in microbiota‐host interactions in intestinal inflammation and glucose metabolism. We found that intestinal epithelial levels of O‐GlcNAc reduce in response to microbial depletion and can be partially rescued by SCFAs in mice. Intestinal epithelial cell (IEC)‐specific knockout of O‐GlcNAc transferase (OGT) in mice causes epithelial barrier dysfunction, microbial dysbiosis, and intestinal inflammation.

Meanwhile, IEC‐Ogt KO mice show increased numbers of intestinal L cells, elevated serum GLP‐1 levels, improved glucose metabolism, and decreased body weight when compared with control mice. On the other hand, IEC‐specific overexpression of OGT downregulates intestinal glucagon gene expression and levels of serum GLP‐1 and insulin.

Fecal transplantation into antibiotic‐treated mice demonstrated that microbial dysbiosis in IEC‐Ogt KO mice is not important for the progression of intestinal inflammation, but is sufficient to drive the improvement of glucose homeostasis and the loss of body weight. These results demonstrate that, in response to microbiota‐derived SCFAs, epithelial O‐GlcNAc signaling maintains intestinal homeostasis by restraining the inflammation and the incretin effect.

Support or Funding Information

This work was partially supported by American Heart Association Scientist Development Grant.
Correspondence of 25‐hepcidin concentrations by ELISA and mass spectrometric methods and their discrimination across healthy and ill subject groups
Authors: Orozco Monica , Arriaga Claudia Lorena , Solomons Noel W. , Schümann Klaus
Published: November 2023

Background

Increasing use of hepcidin as a biomarker of iron homeostasis, especially during infection and inflammation and other iron‐related disorders, calls for affordable and convenient assessment methods capable of precisely quantifying a wide range of hepcidin concentrations.

Objective

To evaluate two different versions of a commercial competitive enzyme‐linked immunosorbent assay (ELISA) kit for bioactive hepcidin‐25 quantitation, with similar dynamic ranges but different specificities, within a large range of hepcidin concentrations.

Methods

Plasma samples from 8 apparently healthy adults recruited in Sololá, Guatemala; 8 mildly sick patients attending clinical consultation at Sololá's National Hospital, and 8 end‐stage renal failure juvenile patients undergoing hemodialysis in FUNDANIER, Guatemala City, were collected to represent the widest possible range of continuous hepcidin concentrations in a human context: low (LH), middle (MH) and high (HH) levels. Hepcidin‐25 was quantified with two ELISA kits (DRG® EIA‐5258 & EIA‐5782) and the gold standard weak cation exchange time‐of‐flight mass‐spectrometry (TOFMS) method. Pearson product‐moment correlation coefficient test was applied to the 3 data‐sets to assess statistical dependence between the 3 methods to determine validity and repeatability.

Results

Average hepcidin concentrations (ng/ml) for LH subjects were: 9±5, 10±2, and 155±67; for MH patients: 29±12, 20±11, and 437±283; and for HH patients: 145±130, 212±295, and 3380±3486, with the TOFMS, EIA‐5258, and EIA‐5782 methods, respectively. Pearson rank correlation coefficients between TOFMS & EIA‐5258 and TOFMS & EIA‐5782 (validity) were 0.94 and 0.123, respectively, and between EIA‐5258 & ‐5782 (repeatability), 0.061.

Conclusion

Despite the declared improved specificity of the newest version of the kit (EIA‐5782), the older version (EIA‐5258) revealed a higher validity when compared to the gold standard, making it a better option for the assessment of a wide range of hepcidin concentrations.
Regulation of Inflammation Metabolism of Hibiscus manihot L. Water Extract
Authors: Kim Kyoung Kon , Choe Myeon
Published: November 2023

The study was conducted to investigate candidate materials as anti‐inflammation agent from Hibiscus manihot L. water extract (HMWE). Activities of HMWE with the final concentration of 1 mg/mL were evaluated on the several inflammation related markers such as the release of proinflammatoty cytokine of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2) in lipopolysaccharide (LPS) treated RAW 264.7 cells.

The results revealed that the HMWE exhibited potent anti‐inflammatory action. HMWE treatment decreased the release NO and inhibited the mRNA expression of TNF‐α, COX‐2, iNOS, IL‐1β and IL‐6 in the LPS‐stimulated RAW 264.7 cells.
IMPACT OF DOSING REGIMEN ON CONSUMPTION OF CALCIUM SUPPLEMENTS FOR PREVENTION OF PREECLAMPSIA AMONG ANTENATAL CARE CLIENTS: A CLUSTER‐RANDOMIZED, NON‐INFERIORITY TRIAL IN WESTERN KENYA
Authors: Omotayo Moshood Olanrewaju , Dickin Katherine , Pelletier David Louis , Mwanga Erick , Kung'u Jacqueline , Stoltzfus Rebecca
Published: November 2023

Background

To prevent pre‐eclampsia, the World Health Organization (WHO) recommends ante‐natal calcium (Ca) supplementation in populations with inadequate habitual intake. The WHO guideline recommends 1.5–2.0 g /d with a dosing regimen that might require 4–5 pill‐taking events when iron and folic acid (IFA) supplements are also taken. We hypothesized that simpler regimens with lower daily dosages might lead to higher adherence, and therefore have the same impact on supplemental calcium intake while costing less.

Methods

We examined the impact of Regimen A, a 3‐dose regimen (500mg × 3, per WHO guidelines), compared to Regimen B, a lower 2‐dose regimen (500mg ×2), on average daily supplement intake, using a parallel, cluster‐randomized non‐inferiority trial in 16 primary healthcare facilities in western Kenya. We enrolled 990 pregnant women between 16 to 30 weeks gestational age. The primary outcome was average daily amount of Ca supplement consumed (mg/d), measured by pill counts assessed at 2 time points, 4 weeks and 8 weeks after recruitment. We carried out intention‐to‐treat analysis using mixed effect models, with regimen as fixed effects, using a non‐inferiority margin of 125 mg/d.

Results

Participants from facilities assigned Regimen A consumed 388 mg/d (95%CI = 341, 434) more supplemental calcium than those assigned regimen B.

Conclusion

Recommending a lower and simpler 2‐dose regimen led to lower impact on estimated supplemental calcium intake than the current WHO‐recommended regimen. Further studies are needed to evaluate how contextual factors influence adherence, clarify the dose‐response relationship of calcium supplementation and preeclampsia prevention and determine cost‐effectiveness of lower and simpler regimens in programs. Trial Registration: NCT02238704

Support or Funding Information

Funding for this research was provided by the Micronutrient Initiative
Consumption of raisin‐containing foods is associated with increased nutrient intake and better diet quality in adult participants (19+ y) from the NHANES (2001–2012)
Authors: Fulgoni Victor L , Painter James E , Carughi Arianna
Published: November 2023

We have previously described the association of raisin consumption with nutrient intake and diet quality; raisin consumers had higher diet quality scores (61.4 ± 1.0 vs. 49.1 ± 0.2) and better intakes of nutrients of public health concern/shortfall nutrients. In this study we examined the association between consumption of raisin‐containing foods (n=149) with nutrient intake and diet quality in adults using data from National Health and Nutrition Examination Survey (NHANES), 2001–2012 (n=29,684). Consumers of raisin‐containing foods (n=4,201; 51.7% female) were defined as having any amount of raisin‐containing foods during the first 24‐hour diet recall. Diet quality was calculated using the Healthy Eating Index‐2010 (HEI). Covariate adjusted (age, gender, race/ethnicity, poverty income ratio, physical activity level, current smoking status, and alcohol intake) regression analyses were conducted using appropriate sample weights; significance was set at p<0.01. For analyses of nutrient intake energy intake was an additional covariate. Energy intake was higher in consumers of raisin‐containing foods than non‐consumers (2241 ± 22 vs. 2054 ± 9). Examining nutrients of public health concern/shortfall nutrients identified by the 2015–2020 Dietary Guidelines for Americans, dietary fiber (18.6 ± 0.2 vs. 16.2 ± 0.1 g/d) and potassium (2758 ± 24 vs. 2656 ± 9 mg/d) were significantly higher in consumers of raisin‐containing foods compared to non‐consumers, while no associations were observed for intakes of calcium and vitamin D. Intakes of vitamin C and E were similar in consumers of raisin‐containing foods and non‐consumers but intakes of vitamin A (719 ± 33 vs. 568 ± 10 μg RAE/d), folate (589 ± 8 vs. 526 ± 4 μg DFE/d), iron (16.6 ± 0.3 vs. 14.9 ± 0.2 mg/d) and magnesium (317 ± 3 vs. 287 ± 1 mg/d) were higher in consumers of raisin‐containing foods. Regarding nutrients to limit, intakes of saturated fat (23.6 ± 0.2 vs. 25.1 ± 0.1 g/day) and sodium (3326 ± 27 vs. 3567 ± 17 mg/day) were significantly lower while added sugar intake was similar in consumers of raisin‐containing foods vs. non‐consumers. Consumers of raisin‐containing foods had higher total HEI scores (58.6 ± 0.6 vs. 54.3 ± 0.4). Regarding HEI sub‐components, the largest differences in sub‐component scores were seen for whole grains (3.3 ± 0.07 vs. 1.9 ± 0.04), whole fruit (2.7 ± 0.06 vs. 2.2 ± 0.03), and sodium (5.0 ± 0.08 vs. 4.2 ± 0.05). In conclusion, consumption of raisin‐containing foods was associated with better nutrient intake and better diet quality in adults.

Support or Funding Information

Funding provided by Sun‐Maid Growers of California.
Validation of Masimo Pronto 7 and Hemocue 201 for hemoglobin determination in children from 1 to 5 years of age
Authors: HUMARAN IGNACIO MENDEZ GOMEZ , Levy Teresa Shamah , del Carmen Morales Ruán María , Tapia Brenda Martinez , Hernández Salvador Villalpando , Ávila Mauricio Hernández
Published: November 2023

Objective

Evaluate the accuracy and precision of Hemocue 201 (Hemocue) and Masimo Pronto 7 (Masimo) devices for measuring hemoglobin in epidemiological studies using having as a gold standard venous blood samples.

Material and methods

In a field sample of 148 children aged 1–5 years were subjects to measure Hemoglobin (Hb) using Masimo, and a capillary blood sample for Hemocue; and a venous blood sample for an automatic analyzer. We constructed regression models with no intercept, for precision and predictability; concordance correlations for accuracy and precision; Band and Altman limits of agreement, and thierarchical linear models for measurement system variance diagnostics.

Results

Both devices under estaimated Hb concentartions compared with gold standard. Hemocue and Masimo devices have regression coefficients of 0.887 and 0.876 with predictability of 98.7% and 98.6% respectively. Concordance correlation coefficients for Hemocue was 0.18341, (p<0.001) and for Masimo 0.16638, (p<0.001). Bland and Altman showed a difference of −1.51 for Hemocue and −1.62 for Masimo. The three level hierarchical linear model shows that 57.9% of the total variance for Masimo came from repeated measure on same subjects.

Conclusions

Hemocue and Masimo measure less concentrations of Hb than the gold standard. The accuracy and presicion of Hb measurements with Hemocue and Masimo devices are very similar in the field. Devices should be used properly in field work, based on enhanced training schedules.
Trends in Consumption of Candy by The U.S. Population between 1971 and 2012: Results from NHANES
Authors: Barraj Leila , Murphy Mary M , Shumow Laura
Published: November 2023

Recent data have shown that candy is a modest source of energy in the average American's diet, but little is known about how the contribution of candy to energy intake has changed over time. This study examined trends in consumption of candy by the U.S. population. Data from day 1 dietary recalls from participants in 11 National Health and Nutrition Examination Surveys (NHANES): NHANES I 1971–1974; NHANES II 1976–80; NHANES III phase I 1988–1991 and phase II 1991–1994; NHANES 1999–2000; and NHANES, What We Eat in America (WWEIA) 2001–2002, 2003–2004, 2005–2006, 2007–2008, 2009–2010 and 2011–2012 were used. Percent consumers of candy (total excluding chewing gum), per capita intake of candy (g/day), per capita energy intake from candy (kcal/day) and a population proportion of percent energy from candy were estimated within each survey period and trends across survey periods were examined using linear and logistic regression and analysis of covariance (ANCOVA). The sample was comprised of children age 2–18 years (n=49,140) and adults age 19–74 years (n=71,139). Across the 4 decades, percent consumers of candy on a given day increased (p<0.05), with 20.5% consumers on a day in 1971–1974 and 24.6% in 2011–2012. The per capita amount of candy consumed and energy from candy increased for the total population and adults, though there were no changes for children. Percent contributions to energy intake from candy were consistent for each population across the 11 surveys, ranging from a minimum of 1.3% to a maximum of 2.4% for the population ages 2–74 y. In analyses limited to data collected in WWEIA components of NHANES (2001–2002 through 2011–2012), percent consumers, per capita candy intake and per capita energy intake from candy significantly decreased (p<0.05) for the total population and among adults 19–74 y. In the WWEIA components among the population 2–74 y, percent consumers of candy ranged from 24.6 to 27.6% and per capita candy intake was 9 to 11 g/day, providing 41 to 50 kcal/day and accounting for 1.9 to 2.2% of total energy intake. Results from this study show that per capita consumption of candy in the United States increased relative to levels in the early 1970s though remained stable as a percent of energy. Additionally, per capita consumption declined over the last decade. The improved methods of data collection in WWEIA, including better capture of potentially forgotten foods, may explain the apparent changes in candy consumption since the early 1970s. Overall, candy remains a relatively small source of energy in the U.S. diet accounting for approximately 2% of energy.

Support or Funding Information

National Confectioners Association
Palm Oil in Myanmar: A Spatiotemporal Study of How Industrial Farming Affects Biodiversity Loss and the Sustainable Diet
Authors: Nicholas Khristopher Mark , Fanzo Jessica , MacManus Kytt
Published: November 2023

Background

Palm oil consumption is not only potentially deleterious to human health, but its production has resulted in 11 million hectares of deforestation globally. Palm oil development and consumption in Myanmar is a burgeoning and under‐researched phenomenon. Importing roughly 394,000 metric tons of palm oil in 2012 alone, the Burmese government has recently pushed for intensive palm oil development to sate domestic demand for consumption and become international market players. Given well‐studied linkages between biodiversity loss and ecosystem instability, this study aims to characterize the nature of deforestation for palm oil production in Myanmar, its effects on the ‘sustainable diet’, and what factors influence it.

Methods

First, a GIS land suitability analysis overlaying spatial data on rainfall, elevation, and slope was conducted in order to identify areas of Myanmar best suited to palm oil tree growth. Second, after narrowing the geographic range, vegetation indices using varying spectral band models in ENVI (specifically, bands 3, 2, 1; 4, 5, 1; and 5, 4, 3) allowed a more granular examination of vegetation phenology over the past 30 years. Lastly, ground‐truthing permitted an in‐person verification of GIS and ENVI results and provided contextual understanding of palm oil development in Myanmar.

Findings

GIS analysis reveals that the Tanintharyi region, one of the most biodiverse regions in Myanmar, proves best suited to palm oil growth. Next, vegetation indices reveal a rapid shift from smallholder farming to what appears to be industrial palm oil plantations all throughout Tanintharyi. Ground‐truthing suggests that plantations are indeed becoming fully industrial, encourage construction of massive processing plants like the Yuzana plant 15km north of Maliwan, and accompany an apparent local embracing of the industrial activity.

Interpretation

If these trends of palm oil intensification continue, then four key outcomes may follow: (1) even higher levels of biodiversity loss, (2) increased access and affordability of edible palm oil, (3) decreased importing of palm oil, and (4) large profits made from selling excess palm oil on the international market. Although the first two may adversely affect low‐income Burmese populations, the latter two may bode well for the domestic economy and international trade partners, thus encouraging competing interests.

Support or Funding Information

Funded by: Global Fellows in Sustainable Development Grant, Columbia University
International food group based diet quality and risk of coronary heart disease in men and women
Authors: Fung Teresa , Isanaka Sheila , Willett Walter
Published: November 2023

Background

Simple diet quality scores have been constructed for low income countries to measure micronutrient adequacy. However, the utility of these scores in high‐income countries have not been examined with regard to clinical outcomes.

Objective

We prospectively examined the association between the Food Group Index (FGI), the Minimal Diet Diversity Score for Women (MDDW), and a newly constructed Prime Diet Quality Score (PDQS) and the risk of coronary heart disease in 3 U.S. cohorts.

Methods

75,055 women (baseline age 43–63), 41,506 men (aged 40–75), and 93,131 younger women (aged 27–44) without a history of cardiovascular disease were followed up to 28 years from 1984 to 2012. Diet was assessed up to 7 times using repeated food frequency questionnaires. The FGI comprised of 8 food groups, the MDDW 10, and the PDQS 21. We computed the 3 diet quality scores for each individual. The association with CHD was modeled with Cox proportional hazard model, controlling for potential confounders.

Results

During follow‐up, we ascertained 2,908 incident CHD in NHS, 3,547 in HPFS, and 505 in NHS II. The FGI was not associated with total CHD in any cohort while the MDDW was significantly but modestly associated with a lower risk of total CHD in NHS and HPFS (total CHD: RR one point increase = 0.95 for both NHS and HPFS, 95%CI=0.91–0.98 for NHS, 0.92–0.98 for HPFS). The PDQS was clearly and significantly associated with CHD in all 3 cohorts (RRs comparing top to bottom quintiles ranged from 0.63 in NHS II to 0.76 in NHS, lower bound of 95% CI ranged from 0.46 to 0.86, upper bound ranged from 0.84 to 0.86). The association did not differ by age.

Conclusion

We found that the PDQS with the most detailed differentiation of healthy and unhealthy foods, was associated with a lower risk of CHD in a high income country. On the other hand, diet quality scores that do not account for unhealthy foods or have little gradation within each food group had limited (MDDW) or no (FGI) association with CHD.
Age at Diagnosis and Duration of Hypertension on the Adherence to the Dietary Approaches to Stop Hypertension (DASH) Diet
Authors: Kim Hyun , Andrade Flavia
Published: November 2023

The DASH diet is a widely recommended diet for individuals with hypertension. Adherence to the DASH diet has been shown to be effective for controlling hypertension, but it is unclear whether age at diagnosis and duration of hypertension have an impact on adherence to the overall diet and nutrient intake. This study examines how age at hypertension diagnosis and time since its diagnosis are associated with the DASH nutrient intake. The data come from the 2007–2008, 2009–2010 and 2011–2012 cross‐sectional National Health and Nutrition Examination Survey (NHANES). Seemingly unrelated regression (SUR) method is used in order to estimate adherence to the DASH diet by age at hypertension diagnosis and time since diagnosis. The outcome is accordance with the DASH recommended intake of nine nutrients (0 to 9 point‐scale DASH score). Age at diagnosis of hypertension is significantly associated with the DASH nutrients. Older age at diagnosis is associated with significant decreases in intake of sodium, cholesterol, saturated fat, total fat, protein, calcium and magnesium and increased intake of fiber. Similarly, duration of hypertension is positively associated with intake of sodium, cholesterol, saturated fat, total fat, protein, calcium and magnesium. As a result, individuals with shorter duration are likely to have lower DASH score, and they less satisfy the DASH target score of 4.5 points. Despite the study findings that individuals with hypertension improve their diet with increased duration of disease, their diet is not still accordant to the DASH diet based on age at diagnosis and its duration. In order to achieve healthy diet and to deliver more tailored educational messages, it is important to first understand what barriers individuals with hypertension have in order to engage in healthy behaviors.
Gestational Weight Gain and Pregnancy Risk Factors among Low Income Women
Authors: Kim Juhee , Chagarlamudi Hemadhanvi , Patil Shiv , Bray Emily
Published: November 2023

Objectives

This study aims to: 1) examine the prevalence of meeting Institute of Medicine (IOM) weight gain recommendations among a low income population, and 2) examine the effects of prenatal factors, especially pre‐pregnancy weight status and nutrition care visit on gestational weight gain (GWG) among low income pregnant women.

Methods

An observational prospective study was conducted with a convenient sample of low income (Medicaid‐insured) pregnant women seeking care in prenatal clinics in Eastern North Carolina (n=108, 52.8% were African American).

Results

The study population exhibits a high prevalence of obesity (24%) and morbid obesity (17%), with an average pre‐pregnancy BMI of 30.1 (SD=9.7). About 60% of participants were receiving care in a high risk clinic. A majority of women exceeded IOM weight gain recommendations (40.7%) while 29.5% fell below recommendations; 63.0% of women used at least one nutrition care visit. While 63% of the overweight group exceeded weight gain recommendations, 72.2% of morbidly obese women fell below the recommended level (p=0.0033). Only 45.4% of participants initiated breastfeeding after birth. Of the mothers who planned to breastfeed, 55.8% successfully initiated breastfeeding. Pre‐pregnancy weight status (P< 0.001) and gestational week at delivery (p=0.0242) were positively associated with GWG (R2=0.363). Potential effects of race, age, nutritional guidance, pregnancy risk status, breastfeeding intention, and initiating breastfeeding at delivery on GWG were not detected.

Conclusions

Low income pregnant women present disproportionately high rates of nutritional risk, inadequate GWG, and low breastfeeding rate. Given these poor nutritional and health outcomes, improved prenatal care focused on nutrition is greatly needed.

Support or Funding Information

East Carolina University Faculty Start‐Up Funding.
Inhibitory effects of DHA and its peroxidation product 4‐HHE on human Colon cancer cells
Authors: Lin Yun‐Hsien , Ganbat Uyanga , Tang Feng‐Yao
Published: November 2023

Background

Fish oil and its constituent, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been known to reduce risk of inflammatory diseases and have anticancer effects on various types of cancers, such as breast, colon, prostate, endometrium and ovary. In epidemiological studies, fish oil is proven to reduce risk of colon cancer. In epidemiological studies, fish oil is proven to reduce risk of colon cancer. In this study we tested effects of DHA and its peroxidation product 4‐hydroxyhexenal (4‐HHE) on colon cancer cells. Lipid peroxidation products may regulate tumourigenesis process and we examined the inhibitory effects of DHA and 4‐HHE on colon cancer cells and investigate if DHA's anticancer effect is due to 4‐HHE.

Materials/Methods

Colon (HCT‐116 and HT‐29) cancer cells were treated with 0, 1, 5, 10, 25 and 50 μM concentrations of DHA and 4‐HHE for 24 and 48 hours and MTT, cell cycle, western blotting assay was performed. For detection of cell signaling pathway, cancer cells were treated for 1 hour with DHA and 4‐HHE with the concentrations mentioned above.

Results

Treatment with DHA and 4‐HHE decreased cell viability in all cancer cells with dose and time dependently. G2/M phase at 48 hours. G2/M phase arrest was seen in MDAMB‐468 cell line at 48 hour time point. Cell cycle regulatory protein expressions were also modulated with both treatments in all cell lines. P‐STAT3 protein expression was reduced with DHA and 4‐HHE treatments dose dependently in every cancer cells.

Conclusion

DHA and its peroxidation product 4‐HHE inhibited cell viability, cell cycle progression and cell cycle regulatory proteins via blockade of p‐STAT3 pathway in human colorectal cancer cells. DHA seemed to be a more effective agent in suppression of colorectal cancer cell growth in comparison with 4‐HHE.
Upregulation of Antioxidant Enzymes by Soybean‐Derived Glyceollins is Independent of p53 Expression in Human Colorectal Cancer Model
Authors: Gwon Yunjeong , Jo Gwang‐Rae , Woo Yaejin , Jeong Gain , Kim Jungeun , Averilla Janice Nullan , Seo Hyelin , Ju Sunghee , Jang Jin Ho , Oh Jisun , Kim Jong‐sang
Published: November 2023

Soybean‐Derived glyceollins were found to induce antioxidant/phase 2 detoxifying enzymes through Nrf2‐mediated signaling pathway, and thus protect cells from exogenous oxidative insult. As Nrf2 signaling pathway has been reported to be suppressed by p53, we hypothesized that Nrf2 activation by glyceollins could also be influenced by p53. Both p53‐wildtype and p53‐knockout HCT116 cells were treated with glyceollins, and then were examined for cell growth and Nrf2‐dependent cytoprotective reactions. Glyceollins treatment increased the expression levels of Nrf2 and its downstream enzymes in both p53‐wildtype and knockout cells in a similar fashion although the expression of p53 and p21 was significantly increased in p53‐wildtype HCT116 cells but not in p53‐knockout cells by glyceollins. In contrast, the treatment of p53‐knockout human colon carcinoma HCT116 cells with either sulforaphane or tBHQ caused dramatic increase in the reporter luciferase gene expression in the cells transfected with antioxidant response element (ARE) and luciferase gene construct, while the compounds led to marginal increase in the reporter gene expression in p53‐wildtype HCT116 cells. Moreover, sulforaphane induced cell growth in wild type HCT116 cells that was inhibited by treatment of SnPP, a HO‐1 inhibitor, while glyceollins did not affect the growth of both types of cells. Thus, the crosstalk between Nrf2 signaling pathway and p53 axis were found to be dependent on Nrf2 activators. In conclusion, these observations implicate the necessity of customized anticancer strategies depending on p53 status as well as the types of Nrf2 inducers.

Support or Funding Information

This study was funded by National Research Foundation (Grant No. R2014R1A2A2A01005773), Ministry of Science, ICT and Future Planning, Republic of Korea