bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination therapies in hormonally‐regulated tumors
Authors: Park Margaret A.
Published: June 2021

The objective of the present studies is to determine the efficacy of combination OSU‐03012 and lapatinib treatment specifically in a model of anoikis resistant (AnR) breast and prostate cancers. The Cox‐2 inhibitor Celecoxib has been reported to possess chemopreventive and chemotherapeutic properties, specifically in hormonally‐regulated tumors. We here report that a potent celecoxib derivative compound, OSU‐03012, causes strong induction of cell death in breast and prostate carcinoma cells, but not primary cells when combined with Lapatinib (GW572016, Tykerb, GSK), an ErbB1/2 dual inhibitor, which is already FDA approved for the treatment of advanced breast cancer. One of the first barriers to metastasis is resistance to anoikis, a form of matrix‐dependent cell death which prevents shed tumor cells from colonizing elsewhere. We show that combination treatment of breast and prostate tumor cells in vitro induces cell death in a synergistic fashion. This killing is achieved partially via induction of ER stress, as cell death is decreased in PERK−/− and dnPERK‐transfected cells, and leads to autophagy, as measured by LC3‐GFP‐positive vacuoles. In addition, the combination retains its synergy when cells are induced to be resistant to anoikis.
Comparison of the Smac based peptides and Smac protein in antagonizing caspase‐3 and ‐7 inhibition by the BIR12 and BIR123 domains of XIAP
Authors: davoodi jamshid , Abhari Behnaz Ahangarian , Balalaei Saeed
Published: June 2021

XIAP prevents apoptosis through inhibition of caspase‐9 by the BIR‐3 and caspases ‐3 and ‐7 through the BIR2 domain. SMAC which is released from the mitochondria competes with caspases in binding to XIAP unleashing caspase activity and causing cell death. SMAC peptides and protein were used to investigate their ability in relieving the executioner caspase activities inhibited by both the BIR12 domains and the BIR123 domains of XIAP. Furthermore, the potency of these peptides was compared to the Smac protein in antagonizing XIAP. AKPD, ANPR, SGVD, AVPI peptides and the SMAC protein were preincubated with the XIAP domains and the activity of caspases was studied in the presence of these mixtures. Moreover, the ability of these peptides in preventing the interaction of BIR12 domain with the large and the small subunits of executioner caspases was studied. It was observed that the Smac protein by far is the most potent agent in reversing caspase inhibition. In addition, Caspase‐3 inhibition by XIAP domains was more sensitive to SMAC peptides than that of caspase‐7. These results indicate that under conditions of extensive XIAP cleavage and involvement of caspase‐7 as the driving force for execution of apoptosis, Smac, and by extension Smac based anticancer agents, cannot be effective in inducing cell death.
Anti‐apoptotic Bcl‐2 uses not only the BH1‐3 groove but also the BH4 region to bind and inhibit pro‐apoptotic Bax oligomerization
Authors: ding jingzhen , Zhang Zhi , He Feng , Lin Jialing
Published: June 2021

Bcl‐2 family proteins regulate permeabilization of mitochondrial outer membrane, the commitment step of apoptosis which is often impaired in tumor cells. In particular, pro‐apoptotic Bax form oligomeric pores in the membrane to initiate apoptosis, whereas anti‐apoptotic Bcl‐2 or Bcl‐XL inhibits Bax oligomerization. Complex structures of Bcl‐2 family proteins determined in solution suggest that a groove on Bcl‐2 formed by the Bcl‐2 homology region 1–3 (BH1‐3) binds to the BH3 region of Bax. However, the structure of Bcl‐2‐Bax hetero‐complex in the membrane is elusive. We used site‐specific photocross‐linking to capture Bax‐Bcl‐2 or Bax‐Bcl‐XL hetero‐complex formed in membrane surrogate (detergent micelles) or real membrane, respectively. Many of the resulting photo‐adducts were formed by the photo‐reactive probes located in the BH3 region of Bax and the BH1‐3 groove of Bcl‐2, supporting that complex model proposed by the structural studies. However, Bax‐Bcl‐2 dimer‐specific photo‐adducts were also detected from probes located in other regions including the helix 6 of Bax and the BH4 region of Bcl‐2, suggesting an additional interface in the hetero‐dimer. Surprisingly mutations in the BH3:BH1‐3 groove interface inhibited the interactions in the helix 6:BH4 interface, and vice versa. The mutation also abolished the Bcl‐2 inhibition of Bax oligomerization. Therefore, Bcl‐2 binds to Bax through two interdependent interfaces to inhibit Bax oligomerization in the membrane surrogate. Preliminary studies of Bcl‐XL‐Bax dimer formed in liposomes indicate that the same mechanism may be used for the hetero‐complex formed in real membranes. Further studies are under way to test this hypothesis. (The project is supported by the NIH grant GM062964 to J.L.)
Aberrant expression of Glia Maturation Factor in Human PD brain
Authors: Zaheer Asgar , Thangavel Ramasamy , Anantharam Poojya , Wynn DonRaphael , Sahu Shailendra K , Zaheer Smita
Published: June 2021

Glia maturation factor (GMF) is an inflammatory protein, discovered in our laboratory, plays a major role in the pathogenesis of CNS inflammatory diseases. In the present study we demonstrate a significant up regulation of GMF in human PD brain. Human brain tissues were obtained from autopsy at University of Iowa Deeded Body Program. For the comparison, we examined brain tissue from five cases with clinically diagnosed and neuropathologically confirmed Parkinson's disease and six age‐matched non‐PD controls. Representative images showing degenerating TH+ neurons/fibers associated with activated microglia and astrocytes in the autopsied brain from PD case compared with age‐matched non‐PD controls. In the substantia nigra of patients with PD, GMF appears to be localized to astrocytes and dopaminergic neurons. We also estimated GMF protein levels in PD brains. We demonstrated a significant increase (over 10 fold) in GMF concentration in the SN and STR of PD patients compare to non‐PD controls. Thus, our results provide strong evidence that under conditions of neurodegeneration in PD the expression of GMF is significantly upregulated. (Supported by VA Merit Review award and NIH/NINSD grant NS‐47145)
Valproic acid suppresses interleukin‐1β‐induced microsomal prostaglandin E2 Synthase‐1 expression in chondrocytes
Authors: Zayed Nadia , Chabane Nadir , Elmansouri Fatima Ezzahra , Martel‐Pelletier Johanne , Pelletier Jean‐Pierre , Fahmi Hassan
Published: June 2021

INTRODUCTION

Microsomal prostaglandin E2 Synthase (mPGES)‐1 catalyzes the terminal step in the biosynthesis of PGE2. Early growth response factor‐1 (Egr‐1) is a key transcription factor in the regulation of mPGES‐1. In the present study we examined the effects of valproic acid (VA), a histone deacetylase (HDAC) inhibitor, on interleukin (IL)‐1β‐induced mPGES‐1‐expression in human chondrocytes.

METHODS

Chondrocytes were stimulated with IL‐1 in the absence or presence of VA, and the level of mPGES‐1 protein and mRNA expression were evaluated using Western blotting and real‐time reverse‐transcription polymerase chain reaction, respectively. The mPGES‐1 promoter activity was analyzed in transient transfection experiments. Egr‐1 recruitment to the mPGES‐1 promoter were evaluated using chromatin immunoprecipitation (ChIP) assays.

RESULTS

VA dose‐dependently suppressed IL‐1β‐induced mPGES‐1 protein and mRNA expression as well as its promoter activation. Treatment with VA did not alter IL‐1‐induced Egr‐1 expression, nor its recruitment to the mPGES‐1 promoter, but prevented its transcriptional activity.

CONCLUSION

Our study demonstrates that VA inhibits IL‐1‐induced mPGES‐1 expression in chondrocytes. The suppressive effect of VA was not due to reduced expression or recruitment of Egr‐1 to the mPGES‐1 promoter.
Prostaglandin D2 enhances interleukin ‐1β‐induced cyclooxygenase‐2 expression in osteoarthritic cartilage
Authors: Zayed Nadia , Chabane Nadir , Elmansouri Fatima Ezzahra , Martel‐Pelletier Johanne , Pelletier Jean‐Pierre , Fahmi Hassan
Published: June 2021

OBJECTIVE

To investigate the effects of prostaglandin D2 (PGD2) on interleukin‐1β (IL‐1beta)‐induced cyclooxygenase (COX)‐2 expression in human cartilage and the signalling pathways involved in these effects.

METHODS

chondrocytes were stimulated with IL‐1 in the presence or absence of PGD2, and expression of COX‐2 protein was evaluated by western‐blotting. Messenger RNA (mRNA) expression was analyzed by real‐time reverse transcription‐polymerase chain reaction. The role of the PGD2 receptors D prostanoid receptor 1 (DP1) and chemoattractant receptor‐like molecule expressed on Th2 cells (CRTH2) was evaluated using specific agonists.

RESULTS

PGD2 increased in a dose‐dependent manner IL‐1‐induced COX‐2 protein and mRNA expression. DP1 and CRTH2 were expressed and functional in chondrocytes. The effect of PGD2 was mimicked by DK‐PGD2 and Indomethacin, selective agonists of CRTH2, but not by BW245C, a selective agonist of DP1. Furthermore, treatment with an anti‐CRTH2 antibody reversed the effect of PGD2, indicating that the stimulatory effect of PGD2 is mediated by CRTH2. Activation of CRTH2 is consistent with the activation of a receptor coupled to a phosphoinositide‐specific phospholipase, suggesting that the effect of PGD2 is mediated by the CRTH2/PIP2/PKC.

CONCLUSION

PGD2 stimulates IL‐1‐induced production of COX‐2 by chondrocytes through the CRTH2/PIP2/PKC signalling pathway.
Effects of kaempferol on the release of proinflammatory mediators by macrophages stimulated with lipopolysaccharide from Prevotella intermedia
Authors: Kim Sung‐Jo , Choi Eun‐Young , Jin Ji‐Young , Lee Ju‐Youn , Choi Jeom‐Il , Choi In Soon
Published: June 2021

In this study, we investigated the effects of kaempferol on the production of inflammatory mediators by murine macrophage‐like RAW264.7 cells stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory periodontal disease, and sought to determine the underlying mechanisms of action. LPS was prepared from lyophilized P. intermedia ATCC 25611 cells by the standard hot phenol‐water method. Kaempferol suppressed the production of nitric oxide (NO) and interleukin‐6 (IL‐6) at both gene transcription and translation levels in P. intermedia LPS‐activated RAW264.7 cells. Kaempferol did not reduce NF‐κB transcriptional activity at the level of IκB‐α degradation. Kaempferol blocked NF‐κB signaling through inhibition of nuclear translocation and DNA binding activity of NF‐κB p50 subunit and suppressed STAT1 signaling. Although further research is required to clarify the detailed mechanism of action, we conclude that kaempferol may contribute to blockade of the host‐destructive processes mediated by these two proinflammatory mediators, and could be a highly efficient modulator of host response in the treatment of inflammatory periodontal disease.

“This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010‐0010325)”
Th2 lymphocyte potassium channels in asthma
Authors: Koshy Shyny , Porter Paul , Hu Xueyou , Atik Mustafa A , Hanania Nicola A , Corry David B , Beeton Christine
Published: June 2021

Asthma is characterized by episodes of breathlessness and airway hyper reactivity, often when provoked by allergens. T‐helper type 2 (Th2) lymphocytes are the predominant T cell population in the lungs of patients with asthma and have been linked to asthma pathogenesis. These Th2 cells represent an attractive target for the treatment of asthma. The use of immunomodulators selective for disease‐relevant T cells that do not affect the bulk of the lymphoid compartment would reduce the risk of side effects. We propose Kv1.3 potassium channel blockers for the preferential targeting of lung‐infiltrating Th2 cells. T lymphocytes express two types of potassium channels, Kv1.3 and KCa3.1 during Th1‐mediated chronic inflammatory diseases. We have used whole‐cell patch clamp to show that Th2 cells isolated from induced sputum of patients with asthma up‐regulate Kv1.3 channels upon activation. In contrast, T cells isolated from induced sputum of healthy controls remained Kv1.3low upon activation. In functional assays, we found that T cells stimulated with an allergen are sensitive to a selective Kv1.3 channel blocker. Selective Kv1.3 channel blockers represent attractive targets for the treatment of allergic asthma.

This study is funded by an R56 AI084981‐01A1 from NIH/NIAID to Christine Beeton.
Study of the molecular interaction between RssB Adaptor protein and IraP Anti‐Adaptor protein in Escherichia coli
Authors: Milanesio Paola Andrea , Battesti Aurelia , Mann Jessica , Bougdour Alexandre , Gottesman Susan
Published: June 2021

In exponential phase, the stationary phase sigma factor σS is maintained at low levels by proteolysis; RssB binds directly to σS and targets it to the ClpXP protease. Under stress conditions this process is inhibited, in part by sequestration of RssB by anti‐adaptor proteins. IraP is an anti‐adaptor made after phosphate starvation. We screened for RssB mutants resistant to IraP. The mutants identify a critical and conserved region between amino acids 214–221 in the C‐terminal domain of RssB. In vivo, cells carrying plasmids encoding RssBL214H or RssBA216T were able to degrade σS even in the presence of high levels of IraP. In a bacterial two‐hybrid assay, RssBL214H and RssBA216AT do not interact with IraP, while RssB+ does. In vitro, purified RssB mutant proteins were fully functional for RpoS degradation; RssBwt but not RssBL214H and RssBA216T were inhibited by IraP. Pull‐down analysis confirmed the loss of interaction of RssBL214H and RssBA216T with IraP. Thus, RssBL214H and RssBA216T have lost the interaction with IraP. Because other data suggests that IraP interacts with the N‐terminal domain of RssB, and these mutations are in the C‐terminal domain, we believe these mutations lead to an allosteric change in RssB, blocking the IraP interaction site. This allosteric change may normally be part of the activation cycle allowing RssB to deliver σS to the protease.
Evaluating Antioxidant Efficacy via Changes in the Oxidized Protein Profile in the Zucker Diabetic Fatty Rat
Authors: Myracle Angela Denise , Madian Ashraf , Burgess John R , Ferruzzi Mario , Regnier Fred E , Janle Elsa M
Published: June 2021

Chronic diseases such as diabetes mellitus are associated with increased levels of oxidative stress. The aim of this study was to evaluate the potential of antioxidant supplements to reduce oxidative stress using a newly developed proteomics technique. Zucker diabetic rats were dosed daily with water, ascorbic acid, green tea or ascorbic acid and green tea for 6 weeks. Oxidized plasma proteins were labeled with biotin hydrazide and separated from the abundant non‐oxidized proteins by affinity chromatography. Oxidized proteins were identified by mass spectrometry and quantified via isobaric‐tag for relative and absolute quantification (iTRAQ). One hundred and twenty oxidized plasma proteins were identified and quantified in 5 sets of supplemented animals. F2 isoprostane values were significantly different from control rats at 6 weeks for ascorbic acid and green tea supplemented groups. The study found several acute phase proteins, which are secreted from the liver during the inflammatory state, are decreased with green tea or ascorbic acid in comparison to the control. This proteomics approach may prove useful in evaluating the efficacy of antioxidant supplements to reduce inflammation and oxidative stress.

Supported by a pilot grant from the Purdue University‐University of Alabama at Birmingham Botanical Center for Age Related Diseases funded by the Office of Dietary Supplements and NCCAM Grant P50 AT 00477
The LIM‐homeodomain transcription factor LMX1B supports the maintenance of differentiated podocytes by modulating the actin cytoskeleton
Authors: Burghardt Tillmann , Kastner Juergen , Suleiman Hani , Kubitza Marion , Rascle Anne , Spang Rainer , Wegener Joachim , Moser Markus , Mierke Claudia , Witzgall Ralph
Published: June 2021

Mutations in the LMX1B gene cause a rare autosomal‐dominant disorder affecting the development of the limbs, eyes, brain and kidneys, called nail‐patella syndrome. In order to determine the role of LMX1B in the differentiation and maintenance of the renal filtration barrier we generated inducible podocyte‐specific Lmx1b knockout mice. Already one week after inactivation of Lmx1b in adult mice foot process effacement and rising proteinuria were detectable underlining the physiological significance of LMX1B in the maintenance of differentiated podocytes.

Using a variety of different biophysical assays such as electric cell‐substrate impedance sensing, nano‐scale particle tracking, magnetic tweezer measurements and adhesion assays we were able to demonstrate that LMX1B affects the organization of the actin cytoskeleton. These findings were corroborated by micro array data which reveal LMX1B‐regulated genes encoding actin cytoskeleton‐associated proteins. Our data highlights the importance of LMX1B in fully differentiated podocytes and describes an essential role of LMX1B for the maintenance of an appropriately structured actin cytoskeleton in podocytes. This work was supported by the German Research Council through SFB 699.
TAp63alpha is involved in toll‐like receptor 3 (TLR3) induced apoptosis via death receptors and mitochondria
Authors: Hu Jinyue , Sun Ruili , Zhang Yu , Liu Bei , Jin Miao , Zhang Weijia , Deng Minjie , Liu Xueting , Li Guancheng , Li Yuehui , Zhuo Guohua , Xie Pingli , Duan Zhaojun
Published: June 2021

TLR3 is widely expressed in various cells and has been shown to activate immune signaling pathways by recognizing virus double strain RNA. Recently, it has been reported that the activation of TLR3 induced apoptosis in some cells, but the detailed molecular mechanism is not fully understood. In this study, we found that Poly I:C induced TLR3 dependent cell death in endothelial cells. Poly I:C treatment activated both caspase 8 and 9, indicating that TLR3 triggered the signaling of both extrinsic and intrinsic pathways. Poly I:C treatment up‐regulated TRAIL and DR4/5, resulting in the initiating of extrinsic pathway. Meanwhile, Poly I:C down‐regulated Bcl‐2, up‐regulated Noxa, leading to the priming of intrinsic pathway. A p53 related protein, TAp63alpha was induced by TLR3 activation and contributed to the activation of both intrinsic and extrinsic apoptosis pathways. The cells deficient in p63 gene expression by RNA interference and the cells over expressed DNp63alpha, a dominant negative variant of TAp63alpha, survived TLR3 activation. Taken together, TAp63alpha as a crucial regulator functions downstream of TLR3 in inducing cell death via both death receptors and mitochondria.
TFL, a putative tumor suppressor, negatively regulates NF‐kappa B signaling pathways by deubiquitination
Authors: Huang Shengping , Qi Dongfei , Fu Mingui
Published: June 2021

Activation of NF‐kappa B signaling pathways could induce cellular transformation and proliferation, as well as tumor development. Therefore, inhibition of NF‐kappa B signaling pathways is crucial for tumorigenesis prevention. In this study, we showed that TFL, a putative tumor suppressor, had an essential role in preventing aberrant activation of NF‐kappa B signaling pathway. Western Blot analysis revealed that the expression of TFL was markedly induced in response to TLR2 ligand Pam3CSK4 and TLR9 ligand ODN1826 treatment in macrophages. Further studies demonstrated that over‐expression of TFL significantly inhibited LPS induced NF‐kappa B activation and its responsive inflammatory cytokine production. Furthermore, we demonstrated that over‐expression of TFL could decrease polyubiquitinating of TNF receptor adaptor factors (TRAFs), which are critical for activation of NF‐kappa B signaling pathways, Conversely, Down‐regulation of TFL level had an opposite effect. Taken together, our data suggest that TFL is involved in negative regulation of NF‐kappa B signaling and this regulation is likely deubiquitination dependent. These findings may implicate that TFL potentially repress tumor proliferation by controlling the activation of NF‐kappa B signaling. These works are supported by UMKC Start‐up Fund.
Evidence in Favor of a Novel Excitation‐Contraction Calcium Release Mechanism in Skeletal Muscle L6 Cells
Authors: Pitake Saumitra , Ochs Raymond
Published: June 2021

Our laboratory has provided evidence for the first half of a model to explain both store‐operated or capacitative Ca2+ entry (CCE) as well as excitation‐contraction coupled Ca2+ release (ECC) in skeletal muscle. Here we offer evidence in favor of a model that proposes ECC acts by a relative displacement of the sarcolemmal L‐channel (DHPR) with respect to the sarcoplasmic reticulum‐localized Ryanodine Receptor (RyR). We titrated cells with ryanodine (Ry) which is known to both active (low concentrations) and inhibit (high concentrations) the RyR. We then repeated this titration after two types of treatments: conditions to depolarize the sarcolemma; and alterations in cytosolic Ca2+ levels under non‐depolarizing conditions. Depolarizing conditions, including high extracellular [K+] and field depolarization with solution electrodes, caused a shift in the Ry titration such that lower concentrations elicited both stimulation and inhibition. Addition of the DHPR agonist BAY K‐8644 caused a similar shift, although of smaller magnitude. On the other hand, altering intracellular Ca2+ through direct activation of RyR with the caffeine‐like xx did not cause a shift in Ry sensitivity. Similarly, alterations in exogenous Ca2+ concentration did not change Ry sensitivity. We suggest that these findings are consistent with our “relative displacement” hypothesis for ECC, whereby excitation moves the DHPR to unoccupied RyR, releasing Ca2+ into the cytosol from previously occluded RyR channels.
Crosstalk between the androgen receptor and liver X receptor
Authors: Krycer James Robert , Brown Andrew John
Published: June 2021

High cholesterol levels are associated with prostate cancer development. Androgens promote cholesterol accumulation by activating sterol‐regulatory element binding protein (SREBP) transcription factors. However, SREBPs are in balance with the liver X receptor (LXR; NR1H2/NR1H3), a transcription factor that prevents cholesterol accumulation. Here, we show that LXR activity is downregulated by the androgen receptor (NR3C4). In turn, this reduces LXR target gene expression. This antagonism on LXR is exerted by other steroid hormone receptors, including the estrogen, glucocorticoid, and progesterone receptors. We are currently determining the mechanism, and have eliminated effects on LXR mRNA levels, protein degradation or DNA‐binding. However, the androgen receptor does not require protein synthesis to influence LXR, suggesting a direct antagonism. Overall, this androgen‐mediated antagonism of LXR complements SREBP activation, providing a more complete picture as to how androgens increase cellular cholesterol levels in a prostate cancer setting. Given the crosstalk between other steroid hormone receptors and LXR, hormonal regulation of cholesterol via LXR may occur in a variety of cellular contexts. This research is supported by the Prostate Cancer Foundation of Australia, and JRK is the recipient of the Petre Foundation Scholarship.
Vitamin B12 is inversely correlated with latency of multifocal visual evoked potential in healthy older adults
Authors: Miller Joshua W , Green Ralph , Wilheim Reva , Songster Chris , Green Ari J
Published: June 2021

The visual evoked potential (VEP) is the electrical potential recorded with scalp electrodes over the occipital cortex after sensory stimulation of the visual field. The latency of VEP response is dependent on the integrity of the myelin sheath. Vitamin B12 deficiency causes demyelination that affects peripheral and central nervous system axons leading to varied neurophysiological and neuropathological manifestations. We investigated the relationship between B12 status and multifocal VEP (mfVEP) in healthy older adults without overt neurological deficits (n = 97; age 70 ± 5y). Serum B12 was measured by automated chemiluminescence assay. mfVEPs were performed using a VERIS‐6 system with 120 sectors per recording. Mean B12 for the cohort was 415 ± 221 pmol/L (range: 135–1401 pmol/L). Only one subject had deficient serum B12 (<148 pmol/L). Mean latency of VEP was 123 ± 5 msec (range: 110–139 msec). In subjects with serum B12 <400 pmol/L (n = 54), B12 was inversely correlated with mfVEP latency (r = −0.325; p = 0.02) after controlling for age and sex. These results suggest that serum B12 within the low normal range (148–400 pmol/L) is a significant determinant of VEP latency in healthy older adults. Whether low B12 status predicts increasing VEP latency over time and whether B12 supplements improve VEP latency in older adults remains to be determined.

Funding: NIH CTSA KL2 RR024130, Private Foundation
Acute effects of pistachio consumption on postprandial glucose and insulin levels, oxidative stress, gut satiety hormone responses and endothelial function
Authors: Kendall Cyril W.C. , Campbell Janice , Jenkins Alexandra L. , Jenkins David J.A.
Published: June 2021

Background

Nut consumption has been found to decrease risk of CHD, to improve control of type 2 diabetes and to promote healthy body weights, possibly related to their favorable fat, protein and antioxidant profiles. Previous studies have demonstrated that pistachios when included in meals decrease the postprandial glycemic response of carbohydrate foods.

Methods

20 subjects, 40–65y, BMI>30kg/m2, with metabolic syndrome as defined by NCEP ATP III guidelines were recruited. Each subject participated in a total of 5 breakfast study meals over 5–10wks. Study meal order was randomized and were consumed after an overnight fast. Meal 1 was a control meal of white bread (50g available CHO). Meals 2 (white bread, butter and cheese) and 3 (white bread plus 3oz pistachios) had similar macronutrient profiles. Meals 4 (white bread) and 5 (3oz pistachios alone) had the same amount of available CHO (12g). Capillary finger‐prick and venous blood samples were taken and subjective satiety measures via a visual analogue scale were assessed along with endothelial function over the 3h study periods. Differences were assessed by least squares means with a Tukey adjustment for multiple comparisons.
Energy Expenditure in Urban African‐American Congregants: Baseline data from Healthy Body, Healthy Souls initiative
Authors: Kodish Stephen , Deka Sidhartha , Martins Paula , Rowan Megan , Suratkar Sonali , Gittelsohn Joel
Published: June 2021

It is well documented that many ethnic minorities do not meet national physical activity (PA) recommendations, but it is unclear what factors are related to this inactivity. This cross‐sectional study used baseline data from Healthy Bodies, Healthy Souls, a 3‐year trial to reduce the risk for diabetes in a low‐to‐moderate income, urban African‐American (AA) population centered on churches. We evaluated whether a cohort of non‐diabetic, AA adults (N = 136) from a larger randomized group trial are meeting recommended levels of PA as defined by the American College of Sports Medicine and the American Heart Association. Participants self‐reported PA using the International Physical Activity Questionnaire, long form. Data analysis revealed that the majority (63.2%) of participants did not expend the recommended > 7.5 MET (metabolic equivalents) hours/week (median = 3.48 METs) and there were no differences by gender or age. The data indicated a significant relationship (p = 0.015) between income (>$30,000/year) and PA (OR=3.1, 95%CI=1.2–7.8) demonstrating that while individual risk factors play a role in predicting health‐seeking behaviors, there are larger social patterns associated with engagement in PA.

Grant Funding Source: American Diabetes Association Clinical Research Award
Multi‐Vitamin (MVI) Use in Black (BK) Patients with Heart Failure (HF) is Associated with Higher Vitamin D levels, Lower intact PTH (iPTH), Better Cardiac Function and Exercise Tolerance
Authors: Markell Mariana , Terebelo Sima , Caboral Meriam , Mitchell Judith
Published: June 2021

MVI use is associated with improved health in other populations. We studied MVI use in 44 BK pts from HF clinic, mean age 62±11, BMI 30±7, Ejection Fraction (EF) 34±2, Left Ventricular End Diastolic Diameter (LVEDD) 6.0±0.9. There were 31 men (71%), 27 (64%) income <20K/yr. 23 pts (50%) took multi‐vitamins (HFMVI), with only half recommended by an MD. By t‐test, HFMVI had lower LVEDD (5.6±0.8 vs. 6.4±1.0, p<0.05), diastolic BP (71±10 vs 80±15 mmHg, p<0.05), iPTH (62.0±30.2 vs 91.4±30.8, p<0.05), ionized Ca/ionized Mg ratio (2.33±0.2 vs 2.58±0.2, p<0.05), and higher total 25‐OH Vit D (33.3±13.7 vs 19.1±10.3, p<0.001) and Vit D3 levels (31.0±13.8 vs 18.8±10.2, p<0.001). By Chi‐square, HFMVI pts more likely had Medicaid (p<0.05), & they had better exercise tolerance (p=0.005). There was no difference for gender, income, age, BMI, dairy servings/week, albumin, creatinine, hemoglobin, cholesterol, serum Ca, Mg, or PO4. We conclude: 1. Vit use in BK pts with HF is associated with better BP control, iPTH levels, cardiac, and physical function, but unrelated to other recorded measures of nutrition. 2. Higher use of MVI by Medicaid pts possibly reflects reimbursement issues. 3. The contribution of improved Vit D levels or iCa/iMg ratio is not known. 4. Recommending use of MVI may be a cost effective intervention in pts with HF.
Effects of lifestyle intervention on blood pressure and serum leptin in high blood pressure Korean men
Authors: Kim EunJin , Cho SangWoon , Hwang MyungOk , Paek YunMi , Choi TeaIn , Park YooKyoung
Published: June 2021

The positive relationships between high blood pressure (BP) and obesity have been reported and leptin, adipocyte‐derived hormone, has been known to increase blood pressure. The study aimed to find out the effect of lifestyle intervention on BP in Korean men with systolic BP ≥ 130 mmHg or diastolic BP ≥ 85 mmHg. Fifty‐two men (age 42.5 ± 8.5 yrs) with normal weight (BMIs < 25 kg/m2) and high BP (NH) and forty men (age 42.0 ± 8.4 yrs) with obese (BMIs ≥ 25 kg/m2) and high BP (OH) underwent 5 times of 1:1 intensive counseling during 12 weeks. Anthropometric, blood pressure measurements and 24hr recall were performed, and blood levels of lipids, glucose, leptin, C‐reactive protein (CRP) were analyzed at 0 week and 12 week. In both groups, weight, body mass index, fat, waist circumference, SBP, DBP were significantly decreased after 12 weeks (p < 0.05). Similarly, TC, LDL‐C, CRP and HbA1c levels were decreased (p < 0.05). In the case of subjects with higher than 10 ng/mL of leptin level at 0 wk, percentage change of DBP were negatively associated, but only in NH (p < 0.05). Therefore, these results suggest that upon serum leptin levels at baseline, effects of lifestyle intervention would be different in Korean men.
Registered Dietitian Involvement in Interdisciplinary Rounds and its Effects on Intervention of Nutrition Support in Adult Ventilated Patients
Authors: Frazier Elizabeth , Gonzales Dana , Hays Nicholas , Hakkak Reza
Published: June 2021

Study Objective

To determine the effectiveness of Registered Dietitian involvement in Intensive Care Unit (ICU) Interdisciplinary Rounds on the implementation of nutrition support compared to an ICU where no interdisciplinary rounds take place.

Methods

A chart review was conducted on seventy adult mechanically ventilated patients. Differences between the number of days to initiation of nutrition support between the two groups were evaluated using the independent sample t‐test as well as the mean number of days on the ventilator and length of stay in ICU between both critical care units. A multiple regression analysis was used to predict the correlation between the time elapsed prior to initiation of tube feeding and length of stay in ICU and time spent on the ventilator.

Results

Patients in MICU where interdisciplinary rounds take place received nutrition support 0.5 days sooner (p=.033). In addition, patients who received nutrition support earlier also received two more days of nutrition (p=.104), were extubated one day sooner (p=.015), and were discharged from the MICU one day sooner (p=.023), than those patients whose nutrition support was delayed.

Conclusion

Registered Dietitian involvement in interdisciplinary rounds in the ICU setting can result in earlier initiation of nutrition support, increased time on nutrition support, and decreased length of stay in the ICU.
The association of food purchasing and body mass index (BMI) among African American church members in urban Baltimore, MD
Authors: Robb Katherine , Rubin Michelle , Budd Nadine , Surkan Pamela , Martins Paula , Gittelsohn Joel
Published: June 2021

Diabetes and obesity is highest among African Americans and is associated with increased chronic disease risk and healthcare costs. We aimed to examine food purchasing patterns among African‐American churchgoers in relation to BMI. In 2010, we surveyed 139 adults from churches in urban low‐income neighborhoods of Baltimore. A food purchasing questionnaire was used to assess food items in eight categories (e.g. dairy products, beverages). Items were designated as unhealthy or healthy relative to their fat and sugar content and summed (mean=38.7(19.8); α=0.71 for 38 items; mean=16.23(11.4); α=0.77 for 16 items, respectively). A Mann‐Whitney test was used to determine differences in scores for each food group, for total of healthy foods, and total of unhealthy foods comparing respondents with higher BMI (≥ 25 kg/m2; n=116) and lower BMI (<25 kg/m2; n=23). Respondents with higher BMIs had higher total unhealthy food scores (mean=16.8, p=0.04) than those with lower BMIs (mean=13.3, p=0.04). Both unhealthy (mean=2.9 v. 1.9, p=0.01) and healthy (mean=0.5 v. 0.2, p=0.04) condiments, unhealthy beverages (mean= 3.9 v. 2.5, p=0.03), and healthy meats (mean=9.1 v. 6.4, p=0.02) were purchased more frequently among those with higher BMIs. Results suggest that food choice is important for BMI and that focusing on food choice may be important in efforts to reduce obesity in this population.

Grant Funding Source: American Diabetes Association
Body composition analysis by DXA in a pre‐school population of Argentina
Authors: Rodriguez Patricia N. , Lifshitz Fima , Bermudez Enrique , Suarez Cristina , Argentieri Angela , Reinoso Josefina Martinez , Exeni Ramon , Friedman Silvia
Published: June 2021

Obesity and osteoporosis are worldwide problems causing high mortality and Public Health costs; pediatricians should play an important role in the early recognition by the evaluation of body fat and mineral content. DXA has considered one of the most precise and applicable method for body composition. Good reference data, which is ethnic, age, gender and manufacture specific, are required.

Objective

To obtain bone mineral content (BMC) and density (BMD), and fat mass (FM) reference values in healthy children aged 2 to 5.

Hundred twenty one children (males=62, females=59) from La Matanza, Province of Buenos Aires, Argentina, attending a day care center, were included. There were healthy according to anthropometric (WHO, 2007) and clinical evaluation. BMC (g) and BMD (g/cm2) less head and %BF were measured by Lunar DPX‐L, pediatric software.

Results

BMD and BMC were significantly increased with age (p < 0.000001); independently of gender. Conversely, girls but not boys showed a significant decreased in FM% depending on age. FM% was significantly high in girls (p < 0.000001).

Conclusion

Because the prevention of adult disease is a central goal of pediatrics, it is necessary to establish body composition reference values, in healthy children by DXA.

Awarded by UBACyT O 015.
Adolescents improve healthy‐eating outcome expectancy: Impact of the Baltimore Healthy Eating Zones study
Authors: Shin Ahyoung , Dennisuk Lauren , Martins Paula , Yong Rachel , Rowan Megan T , Cook Micaela , Coutinho Anastasia , Gittelsohn Joel
Published: June 2021

The Baltimore Healthy Eating Zones (BHEZ) study was designed to address the rising prevalence of childhood obesity in low‐income communities in Baltimore City. During the 9‐month intervention, various food‐related activities and materials including taste tests, cooking demonstrations, giveaways, shelf labels, and point‐of‐purchase posters and flyers were introduced in recreation centers and local corner stores to improve food‐related psychosocial indicators and the overall food environment in low income areas of Baltimore. The study was evaluated in 242 African‐American youths aged 10 to 14 and their caregivers recruited from 14 local recreation centers (7 control + 7 intervention). The impact of the intervention on psychosocial indicators was assessed using a survey informed by Social Cognitive Theory, and analyzed through the t‐test in SPSS. When comparing pre‐ and post‐intervention data, we found that youths in intervention zones significantly improved their healthy‐eating outcome‐expectancy scores (p=0.027, Cronbach's α=0.69) compared to those who are in control zones (p=0.953). No significant improvement was observed for healthy‐eating self‐efficacy (p=0.503 for intervention, p=0.472 for control, Cronbach's α=0.60). These preliminary findings show that the intervention was successful in improving certain psychosocial factors among adolescents. Funding: Robert Wood Johnson: 63149.

Grant Funding Source: The Robert Wood Johnson Foundation
The Wichita “One‐Ton” Weight Loss Program: Community Weight Loss and the National Mindless Eating Challenge
Authors: Wansink Brian , Tal Aner , shimizu mitsuru
Published: June 2021

Community level programs of weight loss have had mixed results due to differing levels involvement, contact, and self‐efficacy of the participants. As a test of concept, a six‐month program was developed for 1000 individuals in the Wichita School District that was based on the National Mindless Eating Challenge. For each of six months, each individual was given three different environmental weight loss suggestions (such as use smaller plates, eat dinner without watching TV, drink 12 ounces of water before every meal and snack, and so on) based on their answers to a series of questions. They received weekly reminders and a $100 insurance rebate for completing 6 months of the program.

Dependent variables included monthly measures of absenteeism, medical expenses, doctor visits, along with self‐reported weight loss and well‐being. Analyses will be presented on what types of individuals were most influenced by the program as well as which specific tips are – in combination with others – most associated with self‐reported weight loss.
High bioavailability of zeaxanthin from deuterium labeled spirulina in humans
Authors: Yu Bolan , Wang Jie , Wang Zhixu , Wang Yin , Suter Paolo M , Russell Robert M , Grusak Michael A , Yin ShiAn , Tang Guangwen
Published: June 2021

Zeaxanthin is a predominant xanthophyll in human eyes and its consumption may reduce the risk of cataracts and age‐related macular degeneration. To determine zeaxanthin bioavailability from spirulina, it was grown in nutrient solution with deuterium oxide for carotenoid labeling. A single servings (4.0–5.0 g) containing 2.6–3.7 mg of zeaxanthin were consumed by 14 healthy male volunteers (4 US Caucasian and 10 Chinese) with 20 g fat. Serum concentrations of total zeaxanthin were measured by using HPLC and enrichment of labeled zeaxanthin was determined by using LC‐APCI‐MS. The intrinsically labeled spirulina zeaxanthin in the circulation was detected at levels as low as 10% enrichment for up to 45 days after intake of spirulina. The average 15‐day area under the serum zeaxanthin response curve to the single dose of spirulina was higher in the US Caucasian subjects 293 nmole‐day/μmole than in the Chinese subjects 197 nmole‐day/μmole (P<0.001). It is concluded that spirulina can serve as a rich source of dietary zeaxanthin with high bioavailability in humans and that there may be racial differences in this bioavailability. (Supported by Nestle Foundation, Lausanne, Switzerland and by the USDA 58‐1950‐7‐707 and 58‐6250‐6‐001).

Grant Funding Source: Nestle Foundation
Consumption of one lutein‐enriched egg per day decreases C reactive protein, plasma insulin levels and improves insulin sensitivity in men and women
Authors: Ata Shymaa M , Barona Jacquline , Fernandez Maria Luz
Published: June 2021

Thirty three subjects (men and women) aged 40 – 75 y were recruited and randomly assigned to consume either 1 egg per day (200 additional μg lutein/d) (EGG), one lutein‐enriched egg (800 additional μg/d) (L‐EGG) or the equivalent amount of egg substitute (0 additional μg lutein)(SUB) for 12 wk. Dietary records and plasma lutein concentrations indicated that subjects complied with the diet. Plasma glucose levels did not change over time in any of the groups. However plasma insulin levels were significantly reduced from 384 ± 150 to 279 ± 161 pmol/L ( P < 0.01) in the L‐EGG group with no changes in the EGG or SUB groups. Similarly, insulin resistance as measured by homeostatic model assessment (HOMA) was reduced from 1.55 ± 0.76 to 1.02 ± 0.82 (P = 0.008) in the L‐EGG group only. Although no changes were observed in Inteleukin‐6, tumor necrosis factor‐alpha or monocyte chemotactic protein‐1 over time, those subjects consuming eggs(EGG and L‐EGG groups) had a significant reduction in CRP (P < 0.01)after 12 wk. Further, 4 of the subjects had metabolic syndrome at the beginning of the intervention (2 EGG and 2 SUB) and only 1 subject from the SUB group remained in this condition. These data suggest that consumption of one egg per day decreases inflammation and the inclusion of additional lutein results in decreased insulin levels and improved insulin sensitivity [Supported by the American Egg Board].
Antioxidant status and its association with elevated depressive symptoms among US adults: National Health and Nutrition Examination Surveys 2005–06
Authors: Beydoun May A , Beydoun Hind A , Boueiz Adel , Shroff Monal R , Zonderman Alan B
Published: June 2021

We examined the relationship of elevated depressive symptoms with antioxidant status as measured by serum levels of carotenoids, retinol+retinyl esters, vitamin C and vitamin E. Data from the National Health and Nutrition Examination Surveys 2005–06 on US adults aged 20–85 years (n=1,798) were analyzed. Depressive symptoms were measured using the Patient Health Questionnaire with a score cutpoint of 10 to define “elevated depressive symptoms”. An inverse association between total carotenoid level and elevated depressive symptoms was found with a reduction in the odds by 38% overall with each SD increase in exposure, and by 34% among women (p<0.05). A dose‐response relationship was observed when total carotenoids were expressed as quartiles [Q4 vs. Q1: OR=0.42; 95% CI:0.24–0.72, P<0.001; p‐ value for trend=0.042], though no significant associations were found with other antioxidant levels. Among carotenoids, β‐carotene and lutein+zeaxanthins had an independent inverse association with elevated depressive symptoms among US adults (per 1 SD OR=0.62, 95%CI:0.39–1.00 and 0.69, 95% CI: 0.50–0.96, respectively, p<0.05). Total carotenoids (mainly β‐carotene and lutein+zeaxanthins) in plasma were associated with reduced levels of depressive symptoms among community‐dwelling US adults.
β‐Cryptoxanthin and lutein mediate inflammatory mediators and cytokines in human chondrosarcoma cells induced with interleukin‐1β
Authors: Kimble Lindsey L , Mathison Bridget D , Chew Boon P
Published: June 2021

Arthritis is characterized by chondrocyte dysfunction resulting in inflammation, matrix metalloproteinase (MMP) production and the progressive degeneration of articular cartilage. β‐Cryptoxanthin (β‐Cr) and lutein (Lu) may downregulate inflammation‐associated factors involved in arthritis. We studied the uptake and protective effects of β‐Cr and Lu, alone and in combination, against chondrocyte dysfunction using SW‐1353 human chondrosarcoma cells induced with IL‐1β. β‐Cr and Lu (10 μmol/L) accumulated in SW‐1353 cells in a time‐dependent manner; β‐Cr and Lu in combination inhibited β‐Cr uptake. Cells were pre‐incubated with 0, 0.01, 0.1, or 1.0 μmol/L β‐Cr, Lu, or a mixture of β‐Cr and Lu for 48 h, then oxidative stress‐induced with 10 ng/mL IL‐1β overnight. Both β‐Cr and Lu, alone and in combination, increased (p<0.05) glutathione peroxidase activity. β‐Cr alone (0.1 μmol/L) decreased (p<0.05) MMP‐13, TNF‐α, inflammatory mediator production and NFκB translocation at the expense of IL‐2 and IFN‐γ upregulation. Lu alone decreased (p<0.05) TNF‐α, inflammatory mediators and NFκB, but did not downregulate MMP‐13. In combination, β‐Cr and Lu decreased (p<0.05) MMP‐13, inflammatory mediators and NFκB without inflammatory cytokine upregulation. Therefore, β‐Cr and Lu protect against degenerative factors upregulated by IL‐1β, likely by scavenging reactive oxygen species required for NFκB activation.
CMO‐II KO mice display altered lipid metabolism compared to CMO‐I KO and wild‐type mice
Authors: Elsen Amy Christine , Ford Nikki Ann , Erdman John W
Published: June 2021

Adult mice lacking the β‐carotene central cleavage enzyme, carotene‐15,15'‐monoxygenase (CMO‐I), have altered lipid metabolism, but little is known about the lipid metabolism in carotene‐9′10′‐monooxygenase II knock‐out (CMO‐II KO) mice. The objective of this study was to examine lipid metabolism in female CMO‐I KO, CMO‐II KO and wild type (C57BL/6Jx129x1/SvJ) mice fed AIN‐93G based diets for 30 days: 20mg lycopene/kg diet from lycopene beadlets, 10% tomato powder, or placebo beadlets. CMO‐II KO mice were significantly smaller (p <.0001) and gained less weight (p <.0001) compared to CMO‐I KO and wild‐type mice. Hepatic lipid content of CMO‐II KO mice was significantly greater compared to CMO‐I KO and wild‐type mice (p <0.05), but serum cholesterol levels were lower in both CMO‐II KO and CMO‐I KO mice compared to wild‐type mice (p <.0001). Expression of adipogenic genes, PPAR‐γ and Acox‐1 was measured in liver and adipose tissue. Hepatic PPAR‐α and adipocyte protein 2 were also measured. Differences were primarily seen between genotypes suggesting that diet did not affect gene expression. Adipose PPAR‐γ expression was greater in CMO‐II KO mice (p <.0001), whereas ap2 gene expression was lower (p <0.05). These results suggest that CMO‐II KO mice have altered lipid metabolism compared to CMO‐I KO mice and wild‐type mice. (Funded in part by NIH grant PHS‐1‐RO1 CA125384.)

Grant Funding Source: NIH
Zinc deficiency increases miR‐34a expression in mice
Authors: Liuzzi Juan , Valencia Katherine , Cao Jay , Gonzalez Armando
Published: June 2021

MicroRNAs play a significant role in the regulation of gene expression in a plethora of eukaryotic systems by binding to complementary regions of specific target mRNAs. To explore the possible changes of microRNA expression induced by zinc deficiency, we compared the global microRNA expression in small intestine of young CD‐1 mice fed either a zinc‐sufficient or zinc‐deficient diet. Microarray analysis revealed up‐regulation of miR‐34a, miR‐1949, miR‐1274a, and miR‐140 in small intestine of zinc deficient mice. Validation study using RT‐PCR showed that zinc deficiency increased miR‐34a expression in small intestine and thymus but did not alter the expression of this microRNA in liver. Moreover, zinc deficiency did not affect the expression of the miR‐34a target SIRT1. The miR‐34 family has been implicated in the p53 tumor suppressor network. Therefore, the up‐regulation of miR‐34a associated with zinc deficiency could be part of an adaptive response to oxidative DNA damage caused by zinc depletion. This project was supported by Florida International University.