bluuebunny/crossref_metadata_2025 huggingface dataset:
Examination of cardiolipin biosynthesis in the diabetic heart
Authors: Croston Tara Lyne , Shepherd Danielle L , Baseler Walter A , Dabkowski Erinne R , Thapa Dharendra , Nichols Cody E , Jagannathan Rajaganapathi , Lewis Sara E , Hollander John M
Published: June 2021

Cardiac complications are a main cause of mortality in diabetic patients. Diabetes mellitus (DM) contributes to mitochondrial dysfunction, with the inner mitochondrial membrane (IMM) being highly affected. The IMM houses both vital processes and an essential lipid environment that contains cardiolipin (CL), which is a phospholipid required for proper mitochondrial function. Two cardiac mitochondrial subpopulations exist: subsarcolemmal (SSM) and interfibrillar (IFM). We previously reported decreased CL content in diabetic IFM, but the mechanisms behind this CL loss are unknown. The goal of this study was to determine how the CL biosynthetic pathway is impacted by type 1 DM. FVB mice were made diabetic by streptozotocin injection. Five weeks post‐diabetic onset, ejection fraction, fractional shortening, and cardiac output were decreased in the diabetic group (*P<0.05 for all three). mRNA content of the CL biosynthetic pathway enzymatic constituents indicated no change between treatment groups. Western blot analysis revealed decreased CL synthase protein content in diabetic IFM, with a concomitant decrease in its activity (*P<0.05 for both). Overall, the results suggest that type 1 DM negatively impacts the CL biosynthetic pathway specifically at CL synthase, and may be a contributing mechanism leading to decreased CL content observed in the diabetic heart.(Supported: NIH‐DP2DK083095, 5T32HL090610)
Haplotype association mapping for exercise training in inbred mice
Authors: Avila Joshua James , Kim Seung Kyum , Massett Michael P.
Published: June 2021

The genetic factors determining the magnitude of the response to exercise training are poorly understood. Therefore, the aim of this study was to characterize the response to exercise training in inbred mouse strains and to identify novel quantitative trait loci (QTL) for changes in exercise capacity. Male mice from 15 inbred strains (n ≈ 6/strain) completed a graded exercise performance test before and after 4 weeks of treadmill running. Changes in time and work (post minus pre) were used to determine training responses. Haplotype association mapping was performed using SNPster to identify QTL. Changes in time and work varied significantly across inbred strains. 129S1 mice showed the greatest increase in time (9.6 ± 1.0 min), which was ~10 fold greater than NZW (−0.7 ± 1.0 min). The difference between these strains for the change in work was approximately 110‐fold (129S1 = 2.01 ± 0.23 kg·m; NZW = 0.02 ± 0.23 kg·m). Eleven significant QTL on four different chromosomes were identified for the change in exercise time. Fifteen significant QTL on nine different chromosomes were identified for the change in work. QTLs were found for both delta work and time on the same chromosomes however; no QTL were common to both phenotypes. The novel QTLs identified in the current study provide new targets for investigating the underlying mechanisms for variation in exercise training responses.

Supported by NIH grant HL085918 to MPM
TNF‐á inhibits stimulation of apolipoprotein A‐IV expression induced by linoleic acid (LA) in Caco2 cells
Authors: Li Xiaoming , Xu Min , Liu Min , Li Yong , Tso Patrick
Published: June 2021

Background

Chronic feeding of a HF diet significantly reduces intestinal as well as hypothalamic apolipoprotein A‐IV (apoA‐IV) gene expression by fat feeding. Since apoA‐IV suppresses food intake, this blunting of gut & hypothalamic responses to fat feeding may contribute to diet‐induced obesity. It is well established that the circulating pro‐inflammatory cytokines are increased by HF feeding.

Aim

The following study was conducted to determine if pro‐inflammatory cytokines are involved in blunting the apoA‐IV responses to fat feeding.

Results & Discussions

LA, an important dietary fatty acid, was used to stimulate apoA‐IV expression in human intestinal Caco2 cells. Cells were pre‐treated with or without human recombinant TNF‐á, IL‐6 or both before the addition of LA to stimulate apoA‐IV expression. ApoA‐IV mRNA levels were measured by real‐time RT‐PCR. LA stimulated apoA‐IV expression markedly in a dose and time dependent manner. Pre‐treatment with the cytokines for 48 or 72 h, especially with TNF‐á, significantly reduced the mRNA of apoA‐IV induced by LA.

Conclusions

We conclude that pro‐inflammatory cytokines, especially TNF‐á, are responsible for blunting of apoA‐IV response to fat feeding. Because of apoA‐IV's role in satiety, this interaction between circulating pro‐inflammatory cytokines and apoA‐IV may contribute to diet‐induced obesity. Supported by NIH DK 59630, DK 92138, and DK 76928.
Curcumin consumption reduces gut microbial diversity among patients with colorectal adenomas
Authors: McLauchlin April , Araujo-Perez Felix , McCoy Nikki , Smith Kevin , Sandler Bob , Asher Gary , Keku Temitope
Published: June 2021

Preclinical studies suggest a role for curcumin in prevention of CRC, but there are few human studies to confirm its effects. Much of our diet is metabolized by gut bacteria, and bacterial dysbiosis is associated with colorectal adenomas, CRC precursors. We hypothesized that curcumin alters the gut microbiota. We assessed the composition of mucosally‐adherent bacteria in participants with (21 case) and without adenoma (14 control) before and after curcumin intake (4g/day for 4 weeks). Non‐prepped, rectal mucosal biopsies were used to assess bacterial profiles by terminal restriction fragment length polymorphism as well as qPCR of common gut bacterial groups. Bacterial diversity was reduced at follow‐up compared to baseline (p= 0.03). We observed reduction in copy numbers of all bacterial groups among cases following curcumin intervention; 47% E. coli, 30.7% Clostridium, 33% Bacteroides, 26% Eubacterium, 22% Bifidobacterium, and 20% Lactobacillus. Curcumin administration can reduce the adherent bacterial diversity in patients with colonic adenomas. Further understanding of the relationship between bacterial diversity and CRC may support a role for the chemopreventive properties of curcumin. Funding support by NIH P30 DK 034987, R01 CA136887, R01 CA044684, P50CA106991.
Exercise capacity and oxygen transport in native Tibetan highlanders with high‐ compared to low‐hemoglobin concentration
Authors: Simonson Tatum S. , Wei Guan , Wagner Harrieth , Wuren Tanna , Yan Ma , Qin Ga , Ge RiLi , Wagner Peter D.
Published: June 2021

Evidence suggests elevated [Hb] at high altitude is a non‐advantageous, possibly misguided, response to high‐altitude hypoxia. In support of that, lower [Hb] is often observed in native high‐altitude resident Tibetans. To determine whether [Hb] in Tibetans is associated with peak VO2 and/or changes in particular step(s) of the O2 transport chain, we compared ventilation, lung diffusional conductance, cardiac output and systemic O2 delivery, and muscle O2 diffusional conductance in 21 Tibetan males with [Hb] ranging from 15.2 g/gl to 22.9 g/dl [Hb] by measuring their ventilation, VO2 and VCO2, heart rate, cardiac output, and arterial PO2, PCO2, pH, P50, and O2 saturation at peak exercise on a cycle ergometer. [Hb] showed a significant negative relationship with VO2/kg (r= −0.45, p< 0.05), cardiac output/kg (r= −0.54, p < 0.01), and diffusion capacity in muscle (DM/kg: r= −0.44, p<0.05) but not lung. Furthermore, VO2/kg was highly positively correlated with DM/kg (r=0.84, p< 2×10‐6), QT/kg (r=0.76, p < 7.5×10‐5), and arterial [H+] (r= 0.52, p < 0.02), and DM/kg was related to QT/kg (r=0.43, p < 0.051). These trends suggest that genetic mutations resulting in reduced [Hb] may convey an advantage in exercise capacity, possibly via higher cardiac function, ventilation, and diffusion capacity in the muscle and support the emerging hypothesis that the polycythemia of altitude is a misguided response to low cellular PO2.
Polycystin‐1 stimulates skeletogenesis via TAZ‐mediated activation of RunX2
Authors: Merrick David Michael , Wu Jingshing , Baggs Julie E , Hogenesch John B , Caplan Michael J
Published: June 2021

Polycystin‐1 (PC1) plays an important regulatory role in bone growth and development, as evidenced by decreased bone density found in Pkd1 mutant mice. The activity of the transcription factor RunX2, the master control gene for osteoblast differentiation, is downregulated in Pkd1 mutant mice, suggesting a relationship between PC1 and RunX2. The mechanism of RunX2 activation by PC1, however, has not yet been established. We have shown that the carboxy‐terminal tail of PC1 (PC1‐CTT) is released by a γ‐secretase‐mediated cleavage and traffics to the nucleus, where it regulates the activity of nuclear signaling proteins. Using a novel ‘Co‐Activator Trap’ screen consisting of a library of Gal‐4 tagged transcription factors, the activity of which can be monitored by luciferase production, we identified the transcriptional co‐activator TAZ (Wwtr1) to be highly stimulated by the PC1‐CTT. The PC1‐CTT strongly stimulates RunX2 activity in a TAZ‐dependent manner, and enhances the ability of TAZ/RunX2 to recruit the transcriptional co‐activator p300. Loss of the two Pkd1 alleles in zebrafish results in a significant decrease in bone density, which can be partially rescued with reintroduction of the PC1‐CTT. TAZ is an essential co‐activator of RunX2 activity and may thus represent the missing mechanistic link between PC1 and RunX2.
ATP mediates flow‐induced nitric oxide production in thick ascending limbs by activating luminal and basolateral P2 receptors
Authors: Cabral Pablo , Garvin Jeffrey L.
Published: June 2021

In the thick ascending limb (TAL) ATP mediates flow‐induced nitric oxide (NO) production via purinergic type 2 receptors (P2r) activation. Both P2r subtypes, P2X and P2Y, are differentially expressed in the luminal (LL) and basolateral (BL) sides of the TAL. We hypothesized that ATP mediates flow‐induced NO production in the TAL via activation of both LL and BL P2r. We measured NO production in isolated and perfused rat TALs using the fluorescent dye DAF FM. Increasing luminal flow from 0 to 20 nL/min stimulated NO production from 17±15 to 130±34 arbitrary units (AU)/min (p < 0.04; n=7). The P2r antagonist suramin (300 μmol/L) reduced flow‐induced NO production by 83 ± 25 % (p < 0.03; n = 5) when added to both LL and BL sides. Luminal hexokinase plus glucose (HK + GL) decreased flow‐induced NO production from 205.6 ± 85.6 to 36.6 ± 118.6 AU/min (p < 0.02; n=7). Basolateral HK + GL reduced flow‐induced NO production from 186.4 ± 45.7 to 30.9 ± 38.4; p <0.005; n=6). The P2Xr selective antagonist NF023 (200 umol/L) prevented flow‐induced NO production when added to the BL side (from 286.1 ± 8.1 to −23.5 ± 17.3; p <0.01; n=6). Luminal NF023 did not affect flow‐induced NO production. We conclude that ATP mediates flow‐induced NO production in the TAL likely via activation of P2Yr at the LL and P2Xr at the BL side.
Physiological activation of Renal‐Angiotensin System (RAS) by low salt diet does not cause kidney injury
Authors: Prieto Minolfa C , Shao Weijian , Demers Sara , Seth Dale M , Navar L Gabriel
Published: June 2021

While increased intrarenal angiotensin (Ang) II is implicated in the development of renal injury in AngII‐dependent hypertension, the changes that occur when Ang II is increased physiologically by low salt (LS) diet have not been delineated. To evaluate the effects of high intrarenal AngII on renal injury elicited by a physiological stimulus, a LS diet (0.03% NaCl, N=6) was given to SD rats for 13d and tissues were compared with rats fed a normal salt (NS) diet (0.3% NaCl, N=6) and rats chronically AngII infused (80ng/min x 13d; N=5). By day 12, SBP was not different from NS rats (118±4 vs. 113±2 mmHg) but was lower than AngII rats (175±10 mmHg). Plasma and kidney AngII levels were greater in rats fed a LS diet than rats with NS (Plasma:154±49 vs. 33±10 fmol/ml; Kidney: 435±57 vs. 265±12 fmol/g) and similar to those in AngII rats (179±56 fmol/ml; 408±196 fmol/g). Glomerular expansion, glomerular and tubular cell proliferation, and macrophage infiltration were not different or slightly less intense in kidneys from LS rats compared to NS rats. However, glomerular and tubulointerstitial fibrosis were greater in LS rats (p<0.05). In contrast, all these markers were markedly augmented in AngII‐infused rats (p<0.001). In conclusion, high intrarenal AngII due to LS diet causes only modest kidney injury changes suggesting that intrarenal AngII must synergize with other factors in AngII‐dependent hypertension to cause kidney injury.
Post natal impact of maternal tryptophan deficiency on central CO2/PH chemosensitivity
Authors: Mosher Bryan Patrick , Iceman Kimberly , Harris Michael
Published: June 2021

Serotonergic dysfunction is thought to enhance vulnerability to Sudden Infant Death Syndrome (SIDS) by compromising critical homeostatic reflexes. Rat dams fed a tryptophan deficient diet produce pups with low tissue serotonin (5HT) had a reduced ventilatory sensitivity to inspired CO2 in vivo. We use a perfused in situ brainstem model derived from pups of dams fed either a control or tryptophan deficient diet, to test the hypothesis that developmental tryptophan deficiency alters central CO2/pH chemosensitivity. Pups (P21‐P83) developmentally exposed and maintained on the experimental diet had decreased ventilatory responses to arterial hypercapnia. Results indicate that central chemosensitive mechanisms are influenced by this treatment. We have proposed that raphé 5HT and GABA mediated mechanisms contribute to central CO2/pH chemosensitivity. Current experiments indicate that these mechanisms continue to contribute to the residual chemosensitivity remaining after tryptophan deficiency. These data further illustrate the contributions of 5HT dysfunction to SIDS vulnerability and enhance our understanding of the impacts of pre and postnatal nutrition. Supported by NIH 2U54NS041069‐06A1 (NINDS), and 5P20RR016466 (NCRR).
Human Stn1 protects telomere integrity by promoting efficient lagging‐strand telomere synthesis
Authors: Huang Chenhui , Dai Xueyu , Chai Weihang
Published: June 2021

Telomeres are critical for maintaining genome stability. The length of telomere is regulated by telomere specific and non‐specific proteins. Stn1, a component of Ctc1/Stn1/Ten1 complex, is known as DNA polymerase α‐accessory factor and plays an unclear role in telomere maintenance. In our studies, Stn1 depletion causes elongated G‐overhang and persistent ssDNA at G‐rich strand in both telomerase‐positive and negative cells. Stn1 depletion shows an increase of fragile telomeres in strands replicated by lagging strand synthesis, implicating that Stn1 is important in efficient replication of lagging strand telomeres. Consistently, BrdU incorporation into lagging telomeres is reduced when Stn1 is depleted. In addition, Stn1 depletion leads to rapid telomere shortening. Cell cycle‐regulated G‐overhang dynamics showed that deficiency of hStn1 delays and compromises C‐strand synthesis that occurs in the late S/G2 phase, leading to persistent lengthening of G‐overhangs at lagging daughter telomeres. We also found that Stn1 interacts with Polα throughout the cycle. ChIP experiments showed that Stn1 depletion results in increased and prolonged Polα association with telomeres, but does not affect the association of Pot1 with telomeres. Our data indicate a key role of Stn1 in telomere replication and maintenance.

Supported by NIH R15GM099008 and American Cancer Society grant IRG‐77‐003‐32
Cell surface expression of xCT is regulated by the Akt signaling pathway
Authors: Chase Leah , Smith Daniel , Schiller NaTasha
Published: June 2021

System xc− is a heterodimeric plasma membrane transporter, comprised of xCT and CD98, which plays a critical role in the maintenance of intracellular glutathione levels. We have previously demonstrated that the cell surface expression of xCT increases by nearly 2‐fold within 10 min of exposure of confluent U‐138MG human glioma cells to H2O2. In addition, we have shown that cell surface expression of xCT is higher in non‐confluent U138MG cultures than confluent cultures. In this study, we sought to determine if the Akt signaling pathway regulates xCT cell surface expression during oxidative stress and cell proliferation, since Akt activation is associated with H2O2 exposure and cell proliferation in other cell types. In support of this hypothesis, we observed a significant increase in Akt phosphorylation in non‐confluent U138MG cells compared to confluent cultures and in confluent cells following a ten‐minute exposure to H2O2 compared to vehicle‐treated confluent cells. Inhibition of Akt signaling with an Akt inhibitor cocktail or transfection with a dominant‐negative mutant of Akt prevented the H2O2‐mediated trafficking of xCT to the membrane in confluent U138MG cells and decreased basal xCT membrane expression in non‐confluent cultures to those observed in confluent cultures. Thus, these data suggests that the cell surface expression of xCT is ultimately regulated by activation of the Akt signaling pathway.
V‐ATPase is a novel evolutionarily conserved cytohesin‐signaling receptor
Authors: Hosokawa Hiroyuki , Dip Phat V. , Merkulova Maria , Bakulina Anastasia , Zhuang Zhenjie , Khatri Ashok , Jian Xiaoying , Randazzo Paul A. , Ausiello Dennis A. , Grüber Gerhard , Marshansky Vladimir
Published: June 2021

Previously, we reported an acidification‐dependent interaction of the endosomal V‐ATPase with cytohesin‐2, a GDP/GTP‐exchange factor (GEF), suggesting that it functions as a pH‐sensing receptor. Here, we have studied the molecular mechanism of signaling between the V‐ATPase, cytohesin‐2 and Arf GTP‐binding proteins. We found that part of the N‐terminal cytosolic tail of the V‐ATPase a2‐subunit (a2N1–402), corresponding to its first seventeen amino acids (a2N1–17), potently modulates the GDP/GTP‐exchange activity of cytohesin‐2. Moreover, this peptide strongly inhibits GEF‐activity via direct interaction with the Sec7 domain of cytohesin‐2. The structure of a2N1–17 and its amino acids F5, M10 and Q14 involved in interaction with Sec7 domain were determined by NMR spectroscopy analysis. In silico docking experiments revealed that part of the V‐ATPase formed by its a2N1–17 epitope competes with the Switch 2 region of Arf1 and Arf6 for a binding on the Sec7 domain of cytohesin‐2. Moreover, the amino acid sequence alignment and GEF‐activity experiments also uncovered the conserved character of signaling between all four (a1‐a4) a‐subunit isoforms of mammalian V‐ATPase and cytohesin‐2. Thus, here we have uncovered an evolutionarily conserved function of the V‐ATPase as a novel cytohesin‐signaling receptor. Supported by grants NIH DK038452, BADERC DK057521–08 to VM and by A*STAR BMRC09/1/22/19/609 to GG.
Contribution of Residue 188 Identity to RhoA and RhoC Membrane Association
Authors: Peyton Nicole , Reicks Amy , Patel Aditi , Ellerbroek Shawn
Published: June 2021

Presence of a negative charge at RhoA residue 188, such as through PKA‐catalyzed serine phosphorylation, has been found to destabilize RhoA membrane association. Closely related RhoC retains an adjacent canonical PKA recognition sequence (KRR), but possesses an Arg residue in place of serine at position 188. Therefore, we propose divergence at residue 188 between these two Rho isoforms directly impacts membrane association. We found transiently expressed RhoC more membrane associated than RhoA when expressed in ovarian cancer cells. Using a residue swap approach, RhoA‐S188R was found more membrane associated than wild‐type RhoA, while RhoC‐R188S had similar membrane association as wild‐type RhoC. At the same time, RhoC‐R188S was more effectively driven from membranes following forskolin treatment than RhoC. Altogether, these data suggest that a positively charged residue at position 188 strengthens RhoC membrane association and provides a mechanism for regulatory divergence.
Use of calcium isotope tracers for screening potential treatments for osteoporosis
Authors: Hohman Emily E , Martin Berdine R , McCabe Linda D , McCabe George P , Jackson George S , Peacock Munro , Weaver Connie M
Published: June 2021

Determining the efficacy of novel osteoporosis therapies and preventive interventions (ie. dietary supplements) is costly and time consuming when using the traditional endpoints of bone mineral density (BMD) or fracture prevention. Calcium isotope tracers offer a relatively cheap and rapid technique to screen potential osteoporosis therapies in both humans and animals. We have developed methods to screen potential anti‐osteoporosis therapies using 41Ca in humans and 45Ca in rats. Following a single dose of the tracer and an equilibration period through one bone remodeling cycle (150d in humans and 30d in rats), the blood and urine clearance of tracer reflects bone turnover, and changes in urine tracer excretion in response to therapy measure changes in net bone turnover. Using this method, efficacy of potential anti‐osteoporosis therapies can be determined in as few as 50 days in humans and 10d in rats, and multiple therapies can be sequentially screened in the same individual. We have utilized this method to compare efficacy of antiresorptives, including bisphosphonates, estrogen, and soy isoflavones, in both humans (Weaver et al. 2009 J Clin Endocrinol Metab) and in rats and have recently confirmed that this method is also suitable for comparing anabolic therapies. These methods will be used in future planned studies to screen botanical products and drug/botanical combination therapies.

Grant Funding Source: NIH, Purdue University
New formulation with potential for the prevention and treatment of Osteoporosis and Osteoarthritis
Authors: Torrent Anna , Montell E. , Vergés J. , Ruhí R. , Dalmau P. , Carceller M.C. , Blanco A. , Terencio M.C. , Ferrándiz M.L. , Alcaraz M.J.
Published: June 2021

Objective

The aim of this study was to investigate the effect of a new formulation in a combined rat model of Osteoporosis (OP) and Osteoarthritis (OA). The nutraceutical formulation (BIS073) contains mainly mucopolysaccharides, a source of calcium and Vitamin D3.

Methods

OP was induced by ovariectomy in female Wistar rats (n=15 rats/group) and 2 weeks after OA was induced by Anterior Cruciate Ligament Transection (ACLT). BIS073 was administered daily (oral gavage) at two doses (93.3 mg/kg/day and 280 mg/kg/day) from week 0 until week 12 after ovariectomy. A Control Group and Vehicle Group were also included. After week 12, animals were sacrificed. For the assessment of OA, histology was performed and cartilage degeneration was evaluated by means of the OARSI score. Bone microarchitecture and density were assessed by microCT.

Results

BIS073 has been shown to induce a statistically significant reduction (approximately 40%) of the cartilage degradation according to the OARSI score. MicroCT revealed that this treatment exerted a positive effect in bone structure, especially at the high dose. In addition, a significant reduction in the pro‐inflammatory cytokines IL‐1β and IL‐17 was observed.

Conclusion

Our data demonstrate that treatment with BIS073 could be an effective strategy to control the progression of experimental Osteoarthritis and Osteoporosis.

Supported by BIOIBERICA S.A, Barcelona, Spain.
Influence of leadership on the systematic identification of child food insecurity in schools
Authors: Fishbein Eliza M. , Fram Maryah S. , Frongillo Edward A.
Published: June 2021

Many of the more than 20% of US children living in a food‐insecure household experience hunger, and currently there is no system to identify these children. Schools are existing systems that could be used for identification because they already confront and respond to food insecurity. This research examined how school leadership influenced whether or how schools could systematically identify children who are food‐insecure. In 3 elementary and middle schools in one school district, we assessed among key actors current practices and attitudes towards food issues, challenges, and leadership. All students (n=763) participated in an assessment about their experiences related to food insecurity. Follow‐up in‐depth interviews with children who affirmed food insecurity guided responses by the schools to resolve the problem through a regular take‐home backpack of food and/or linking the family to other resources. We found that collaborative school leadership promoted buy‐in and ownership from all actors. Top‐down leadership promoted buy‐in but limited ownership, and disinterested leadership allowed individual beliefs to determine practices. School systems provide a scalable way to identify children who are food‐insecure that can contribute to ending child hunger. Funded by Nord Family Foundation.

Grant Funding Source: Nord Family Foundation
The distribution of food insecurity in Mexico
Authors: Levy Teresa Shamah , Mundo‐Rosas Verónica , Cuevas‐Nasú Lucía , del Carmen Morales‐Ruan Ma , Rivera Dommarco Juan A.
Published: June 2021

Objective

To estimate the proportion of Mexican households those suffer food insecurity and their association with some interest variables.

Methods

Data comes from the National Nutrition Survey in Mexico. We used the Latin American and Caribbean household food Security measurement scale (ELCSA) and their association with an index of welfare conditions, allowing categorize households by poverty level, also we included if the head of household or spouse speak an indigenous language.

Results

Information from 40,809 ‐that nationwide expanded represents 29,099,600‐ households was included. From this data we classify 41.6% of such households in the mild food insecurity (FI) category, 17.7% as moderate and 10.5% as severe. Adding the ciphers from the two lowest categories (moderate and severe) it is observed that in the three months prior the interview date, about 8,322,486 households had to reduce the consumed food amount, or in the worst scenario an adult or a children in such house was left without any food throughout the day. Analyzing the data by urban and rural condition we found a 34.5% and 26.2% of moderate and severe food insecurity respectively. Four out of ten households classified as indigenous and belonging to the lower tertile of welfare conditions index reported suffering moderate or severe food insecurity in the three months prior to the scale application.

Conclusions

The proportion of FI in Mexico is high. It is necessary to analyze and redesign the strategies implemented by the State in order to ensure food security in Mexico.
Determining the gut microbiota‐independent effects of prebiotic fiber in diet‐induced obese rats
Authors: Bomhof Marc , Skochylas Heather , Reimer Raylene
Published: June 2021

Prebiotics, which are indigestible carbohydrates that are selectively fermented in the gut, have been shown to improve glycemia, inflammation, satiety, and body weight. The health benefits elicited by prebiotics are believed to be mediated through compositional changes in gut microbiota and associated metabolic activity. The extent to which prebiotics are dependent on gut microbiota for improved metabolic health is not clear. Our aim was to examine the gut‐microbiota independent effects of prebiotics on body weight, adiposity, intestinal permeability, and glycemia in a model of antibiotic‐induced intestinal decontamination. Diet induced obese male Sprague Dawley rats were randomized into 1 of 6 groups: 1) High energy (HE) ; 2) HE+Ampicillin (AMP); 3) HE+AMP+Neomycin (NEO); 4) HE+10% oligofructose (OFS); 5) HE+OFS+AMP; 6) HE+OFS+AMP+NEO (n=10 rats/gp). Decontamination of the gut with AMP and NEO did not limit classical prebiotic effects including reduced body fat and food intake and improved glucose tolerance (P<0.05). Decontamination with AMP, which is known to decrease the beneficial bacteria associated with OFS consumption, prevented prebiotic‐mediated improvements in adiposity and intestinal permeability (P<0.05). Taken together, this data suggests that prebiotics elicit both microbiota‐independent and microbiota‐dependent effects on metabolism in obesity. Funded by CIHR, NSERC, and AIHS.

Grant Funding Source: Canadian Institutes of Health Research
Lathosterol to cholesterol ratio in serum predicts cholesterol lowering response to plant sterol therapy in a dual center, randomized, single‐blind placebo controlled trial.
Authors: MacKay Dylan Stapenhorst , Gebauer Sarah , Baer David , Jones Peter
Published: June 2021

Plant sterol (PS) therapy for LDL‐C lowering has highly variable efficacy across individuals. It has been suggested that cholesterol synthesis levels may affect PS response. A study was conducted to test lathosterol to cholesterol ratio (L/C), a marker of cholesterol synthesis, as a predictor of response to PS consumption. 63 mildly hypercholesterolemic adults, with high (n=24, L/C = 2.03 ± 0.39) or low (n=39, L/C =0.99±0.28) L/C ratio at baseline, consumed either 0 or 2g/d (free sterol) of PS ester in margarine for 28 days in a dual‐center, single‐blind, randomized, crossover design. Plasma lipids, non‐cholesterol sterols, and 7‐α hydroxy‐cholesterol (7αHC) a marker of bile acid (BA) synthesis, were measured at the end of each phase. PS consumption significantly lowered LDL‐C, with a significant interaction with L/C ratio. LDL‐C was lowered in the low L/C group (−0.29 mmol/L 95% CI [−0.39, −0.19] p=<0.0001), but not the high L/C group (−0.04 mmol/L 95% CI [−0.18, 0.09] p=0.4904). 7αHC after PS consumption correlated with LDL response in high L/C group (r=−0.59, p=0.002), but not in the low or combined L/C groups. The L/C ratio predicts reductions in LDL‐C in response to PS consumption. BA synthesis may be associated with PS response in individuals with high cholesterol synthesis. These findings could help in identifying non‐responders to PS therapy. Registered at clinicaltrials.gov as NCT01131832.

Grant Funding Source: CIHR
A randomized controlled trial of genetic information on dietary intake
Authors: Nielsen Daiva , El‐Sohemy Ahmed
Published: June 2021

Personal genetic information has become obtainable as a result of commercial genetic tests, but its effect on dietary change is not clear. We compared the effects of providing DNA‐based dietary advice with general recommendations on dietary intake using a randomized trial. Subjects aged 20–35 years (n=102) completed a baseline food frequency questionnaire (FFQ) and were randomized to an intervention (I) or control (C) group. Subjects in the intervention group were genotyped for the angiotensin‐I converting enzyme (ACE) gene, which has been associated with salt‐sensitive hypertension, and were given personalized advice for sodium intake based on their ACE genotype. The control group was given a general recommendation for sodium intake without genetic information. A second FFQ was collected 3 months later. A significant reduction in sodium intake was observed in subjects in the intervention group who were informed that they carried the risk allele for ACE when compared to the control group (−174.9±89.1 mg/day [I] vs. 225.5±123.5 mg/day [C]; p = 0.008). No difference was observed between subjects who were informed that they did not carry the risk allele and controls (111.2±145.0 mg/day [I] vs. 225.5±123.5 mg/day [C]; p = 0.48). The results suggest that personalized advice based on genetic information may be superior to general advice in motivating individuals to adopt dietary changes.

Grant Funding Source: Advanced Foods and Materials Network
Effectiveness of Insulin Pump use in regulating blood glucose in Type 1 Diabetes Mellitus Patients
Authors: Nemeh‐Saad Nadia M , Mistry Anahita M
Published: June 2021

It is vital for type 1 diabetes mellitus (Type 1 DM) patients to regulate blood glucose. Glycemic control for these patients is achieved by delivering insulin by continuous subcutaneous insulin infusion (CSII) via a pump or by multiple daily insulin injections (MDI). The purpose of this study was to evaluate the effectiveness of CSII compared with MDI, in regulating blood glucose in adult (18–50 yrs) type 1 DM patients. A retrospective comparison of two groups of type 1 DM patients (n=35 per group) was conducted. One group received MDI therapy and the other received CSII therapy. Parameters compared included HgA1C, fasting blood glucose concentrations, total episodes of hypoglycemia, severe and nocturnal hypoglycemia, and diabetic ketoacidosis (DKA). Results indicated a slight but significant decrease in HgA1C (7.19 and 7.04) in CSII patients at 3 and 6 months respectively, compared with patients on MDI (7.46 and 7.29). Furthermore, fasting blood glucose concentrations were lower in CSII (104.5 mg/dl) patients compared to those on MDI (122.4 mg/dl) at 6 months. There was also a decline in the total number of hypoglycemic and nocturnal hypoglycemic events over 6 months in these patients. CSII therapy in this study was more effective than MDI in regulating blood glucose in type 1 DM patients.
Prospective associations of biomarkers of glucose metabolism and obesity‐related cancers in the Framingham Heart Study (1971–2008)
Authors: Parekh Niyati , Lin Yong , Vadiveloo Maya , Hayes Richard , Lu‐Yao Grace , Lin Yong
Published: June 2021

Obesity‐induced aberrations in glucose metabolism are associated with cancer risk. We investigated prospective associations of hyperglycemia with incidence of cancers associated with obesity, in the Framingham Heart Study Offsprings (n=4615; n events=787; 1971–2008; mean age 66.8y in 2008). Serum insulin and glucose were estimated from fasting blood; lifestyle and demographic information was obtained from in‐person interviews. Time‐dependant survival analyses were used to compute hazard ratios (HR) and 95% confidence interval (CI) of cancer incidence, using SAS. After adjusting for age, sex, smoking status, alcohol and physical activity, hyperglycemia (>;110 mg/dl) was associated with 27% increased risk of overall obesity‐related cancer incidence (HR:1.27; CI:1.1–1.5). Risk was 47% (CI:1.1–1.9) and 54% (CI:1.1–2.1) higher among persons with hyperinsulinemia and poor long‐term glycemic control measured by hemoglobin A1c, respectively for tertiles 3 vs 1. Associations were stronger in “ever” smokers (HR:1.41; CI: 1.1–1.8). In gender stratified analyses, associations were stronger among females. Hyperglycemia for 10–20y and 20+y increased risk by 44% (CI: 1.1–1.6) and 86% (CI: 1.5–2.2) of overall obesity‐related cancers, respectively. Hyperglycemia, particularly poor long‐term glycemic control, is a ‘high‐risk’ condition for obesity‐related cancer incidence.
Dietary intakes of children from birth to 24 months: What We Eat in America, NHANES 2007–2010
Authors: Rhodes Donna G , Adler Meghan E , Clemens John C , Goldman Joseph D , Moshfegh Alanna J
Published: June 2021

What We Eat in America, National Health and Nutrition Examination Survey (WWEIA, NHANES) collects dietary intake data on a nationally representative sample of all individuals; however, data release and analysis have mainly focused on Americans ages two and above. Using day one dietary data from WWEIA, NHANES 2007–2010 nutrient intakes were estimated for children, aged 0–24 months (n=1391). The 5‐step USDA Automated Multiple‐Pass Method was used to collect a 24h recall from a proxy knowledgeable about the child's intake. Breast milk (BM), not quantified during the recall, was reported by 19% of the sample. For this research, BM volumes were assigned using assumptions based on amounts typically consumed per day for infants (0–11.9 mo) or per breastfeeding occasion for toddlers (12– 23.9 mo). Mean energy intake for younger infants < 6mo (n=372) was 618 kcal/d. Breast milk, formula/other milk (FM) and other foods (OF) contributed 147 kcal, 438 kcal and 33 kcal, respectively to daily energy. Energy intake increased to 850 kcal/d for older infants 6–11.9mo (n=428); BM, FM and OF contributed 62 kcal, 460 kcal and 328 kcal, respectively to daily energy. For all infants, frequently reported OF included baby foods: rice cereal, oat cereal, apple juice, puffs; plus raw banana. Mean energy intake for toddlers (n=591) was 1211 kcal/d. This data will help eliminate gaps in knowledge about dietary intakes during the first two years of life.

Funding source for this study is USDA
Nutritional Deficits in Juvenile End‐Stage Renal Disease in a Guatemalan Context
Authors: Casimiro Juliana , Lou‐Meda Randall , Solomons Noel W , Schümann Klaus
Published: June 2021

Background

Guatemala is a tropical developing country with a legacy of early child undernutrition and micronutrient deficits. These represent a background setting for any nutritional challenges superimposed by juvenile end‐stage renal disease (ESRD).

Objective

To assess anemia and growth attainment comparatively in hemodialysis (HD) and peritoneal dialysis (PD) patients in Guatemala.

Methods

54 patients (7–20 y), 27 on HD and 27 on PD, constituting most of the dialysis population of the Pediatric Renal Unit of the Roosevelt Hospital in Guatemala City, were measured (height, post‐dialysis weight and blood samples) and assessed for Hb status. Age‐appropriate WHO Hb cut‐offs were adjusted (+0.7 g/dL) for the altitude of 1500 m. Median duration on dialysis was 7 mo. Both groups regularly received Fe supplements, parenterally in HD and orally in PD.

Results

The overall median height‐for‐age (HAZ) score was −2.7, with a mean of −3.1 ± 1.3 in HD and −2.3 ± 1.4 in PD (p=0.16). 93% of the former and 55% of the latter were “stunted” (<−2 HAZ). Hb mean was 9.0 ± 1.9 g/dL in HD and 9.9 ± 2.7 g/dL in PD (p=0.17). Overall, 83% of the subjects were “anemic” on an altitude‐adjusted basis, 96% of HD and 70% of PD.

Conclusions

Linear growth failure and anemia were almost universal, with no differences by mode of dialysis.

Funded by Hildegard Grunow Foundation, Munich
Teaching 3rd & 4th year medical students how to cook: an innovative approach to balance lifestyle modification and medication therapy in chronic disease management
Authors: Leong Benjamin , Abu‐Shamat Layla , Kay Danielle , Monlezun Dominique , Sarris Leah , Harlan Timothy
Published: June 2021

An electronic survey was sent to all Tulane medical students to assess students’ baseline perceptions about perceived competence regarding nutrition counseling. Students were able to rate themselves as ‘totally proficient,’ ‘somewhat proficient,’ and ‘not proficient.’ Proficiency increased between 1st and 2nd year medical students (p=0.02) and between 2nd and 3rd year medical students (P=0.0001). However, no increase in proficiency was observed between 3rd and 4th year medical students (p=0.48). The Tulane University School of Medicine has launched a curriculum for its medical students that teach nutrition science in the context of preparing and cooking food. Beginning in the third and fourth year, students will have the opportunity to take disease‐based seminars (e.g. hypertension) and conduct away rotations with the Dept. of Culinary Nutrition at Johnson and Wales University. The curriculum will include lessons in food preparation using recipes that follow DASH diet guidelines. The survey described above will be given yearly to assess if students participating in this curriculum are different from classmates who did not participate. Research support: Tulane University Center for Culinary Medicine

Grant Funding Source: Tulane University Center for Culinary Medicine
Reduction of metabolic syndrome by a lifestyle‐modification program is accompanied by improvements of aerobic fitness and plasma antioxidant markers
Authors: Moreto Fernando , Manda Rodrigo Minoru , Portero‐McLellan Katia Cristina , Correa Camila Renata , Burini Roberto Carlos
Published: June 2021

Lifestyle change is an effective strategy in the primary care of metabolic syndrome (MetS). To verify the effects of a lifestyle‐modification program (LISC) on MetS and its co‐morbidities, 60 subjects (53yrs, 84% women) clinically approved to attend a 20wks intervention in the LISC “Move for Health” were submitted to weekly nutritional counseling and daily (3–5 times/wk) physical activities. Before and after intervention there were performed anthropometric, clinical, physical (with VO2max test) and laboratorial assessments including plasma analysis of total antioxidant performance (TAP), reduced (GSH) and oxidized (GSSG) glutathione, malonyldialdehyde (MDA) and C‐reactive protein (CRP). For statistical analysis we used paired‐t or signed rank tests with p<0.05 by SigmaStat 3.5 software. The reduction of MetS (47 to 40%) was followed by reductions in waist circumference (97±16 to 94±14cm) and elevations in plasma HDLC levels (47±12 to 49±12mg/dL). VO2max increased (30±5 to 33±5.2mL/kg/min) as well as plasma TAP (50±9 to 52±9%), reduced GSH (5.9±1.9 to 6.9±1.9μmol/L) with a decrease of GSSG/GSH ratio (0.13[0.08–0.17] to 0.10[0.07–0.13]). No differences in insulin resistance (fasting glucose and HOMA‐IR), inflammatory (CRP) and pro‐oxidant markers (MDA and GSSG) were observed. This LISC was effective in lowering MetS probably secondary to raising either cardiorespiratory fitness and/or antioxidant potential.

Supported by CAPES, CNPq
Contrast ultrasound imaging of the aorta does not affect progression of atherosclerosis in ApoE−/− mice
Authors: Smith Brendon W. , Simpson Douglas G. , Sarwate Sandhya , Miller Rita J. , Abuhabsah Rami M. , Erdman John W. , O'Brien William D.
Published: June 2021

Ultrasound Contrast Agents (UCAs) are used clinically to enhance ultrasound imaging of the cardiovascular system. Adverse biological effects have been noted after administration of UCAs, and more research is needed for an understanding of the biological effects of UCAs. Male ApoE−/− mice (8 weeks old, n=38) were intravenously infused with the Definity® UCA (2×1010 UCA/hr) and either exposed to 2.8‐MHz 10‐Hz PRF 1.4‐μs PD 2‐min ED 1.4‐MPa PRPA ultrasound or sham exposed, and then consumed either a chow or Western diet for either 4 or 8 weeks after ultrasound exposure (n=4–5 per group). Plasma total cholesterol was greater in the Western diet group than the chow group for all timepoints after baseline (p<0.0001). Plasma von Willebrand Factor (vWF), a biomarker of endothelial function, was elevated in Western diet animals compared to chow animals (p<0.05). Atheroma thickness was greater in animals consuming the Western diet than in chow‐fed animals (p<0.001), and in animals euthanized after 8 weeks than after 4 weeks (p<0.005). Ultrasound did not affect plasma total cholesterol levels, plasma vWF or atheroma thickness. [Supported by NIH R37EB002641]
Effect of cinnamon on blood glucose, satiety and caloric intake in middle‐aged obese adults
Authors: Chezem Jo Carol , Tickle Samatha , Fernandes Nicolle , Bolin Jocelyn H
Published: June 2021

The objective of this study was to examine the effect of cinnamon on postprandial blood glucose, satiety and subsequent caloric intake in middle‐aged obese adults. Using a crossover design, subjects consumed 50 g available carbohydrate as a breakfast drink with or without 6 g ground cassia cinnamon. Blood glucose and satiety were evaluated at 0, 15, 30, 45, 60, 90 and 120 minutes. Ad libitum caloric intake was estimated from a meal served at 240 minutes. Twenty‐six adults (9 males and 17 females), aged 40–63 years, completed the study. Paired t‐test, with Bonferroni correction, assessed differences in blood glucose, satiety and caloric intake between the control and cinnamon conditions. There were no significant differences in blood glucose and satiety values at any time point between the two conditions (p>;0.05). Subsequent caloric intake was similar in the two conditions (p>;0.05). The lack of agreement with earlier research may be related to differences in study populations and/or study foods.
Cellular pyridoxal phosphate concentration influences amino acid profiles and presence of hydrogen sulfide biomarkers in cultured HepG2 cells
Authors: DeRatt Barbara Neal , Ralat Maria , Kabil Omer , Banerjee Ruma , Gregory Jesse F.
Published: June 2021

Pyridoxal phosphate (PLP) functions as a coenzyme in cellular one carbon metabolism and many other roles in amino acid interconversion and catabolism. The PLP‐dependent transsulfuration enzymes, cystathionine beta‐synthase and cystathionine gamma‐lyase, have been implicated in hydrogen sulfide (H2S) production that is concurrent with the formation of lanthionine and homolanthionine. Thus, cellular PLP availability may influence the concentration of many amino acids including these H2S biomarkers. In this study, we examined amino acid profiles in HepG2 cells cultured six weeks in supraphysiological to deficient concentrations (2000, 200, 50, and 10 nM) of pyridoxal (PL). Fluorometric HPLC was used to quantify the amino acids as danysl derivatives. Assuming the 50 nM PL reflects nutritional adequacy, the deficient 10 nM cells showed higher concentrations of arginine, asparagine, glutamine, serine, threonine, glycine, alanine, methionine, valine, leucine, lanthionine, and lysine (P<0.05). Results indicate that restriction of vitamin B6 can alter amino acid profiles, including biomarkers of H2S synthesis, in HepG2 cells.

Grant Funding Source: NIH Grant DK072398
Wild blueberry‐enriched diet affects α1‐adrenergic induced vasoconstrictor response in the aorta of obese Zucker rats
Authors: Vendrame Stefano , Kristo Aleksandra S. , Daugherty Allison , Schuschke Dale A. , Klimis‐Zacas Dorothy
Published: June 2021

This study investigates the effects of wild blueberry (WB, Vaccinium angustifolium) on arterial contractile response to the α1‐adrenergic agonist phenylephrine (Phe) in 8 week old obese Zucker rats (OZR). Twenty OZR were randomly assigned to a control (C) or an 8% WB diet for 8 weeks. Vascular studies were conducted in isolated aortic ring preparations to measure vasoconstriction induced by Phe, 10–8 to 3×10–6M. Plasma nitric oxide (NO) and aortic concentration of prostacyclin (PGI2) and thromboxane A2 (TXA2) in the effluent was determined.

Obese Zucker rats exhibited a reduced response to Phe‐induced vasoconstriction, possibly due to a compensatory overproduction of NO under inflammatory conditions. The WB diet partially restored Phe‐induced constrictor responses, compared to their lean littermates, by increasing the maximal force developed (0.55±0.02 g WB vs 0.43±0.02 g C, p≤0.05)

Plasma NO was significantly attenuated (22.1±1.1 μmol/L, WB vs 25.6±1.4 μmol/L, C, p≤0.05) with the WB diet. Aortic effluent TXA2 levels were not significantly altered, while PGI2 concentration significantly increased (766.5±92.2 pg/mg WB vs 571.7±37.8 pg/g C aorta, p≤0.05).

In conclusion, WB consumption significantly altered vasomotor tone in response to an α1‐adrenergic agonist in the OZR aorta and modulated plasma NO and aortic effluent PGI2.

Grant Funding Source: Wild Blueberry Association of North America
A flavonoid‐rich apple extract inhibits growth of HCT116 human colon cancer cells
Authors: Morton Andrew , Cao Loan , Bourquin Leslie D.
Published: June 2021

Colorectal cancer is one of the most prevalent types of cancer that can be influenced by diet. Many different flavonoids have been shown to inhibit colon cancer, and apples, rich in flavonoids, are one of the most common flavonoid sources in the American diet. We investigated the effect of an apple extract from apple pomace, containing many different flavonoids, on the growth of HCT116 human colorectal cancer cells. Apple extract was created by extracting apple pomace with ethanol and was concentrated by rotary evaporation before storage. Before addition to the media, the extract was further evaporated by rotary evaporation and filtered. HCT116 cells were seeded in 24‐well plates and treated with increasing concentrations of the apple extract. Cell number was assessed by quantification of total DNA content. After 72 hours of treatment, the apple extract caused a dose‐dependent reduction in cell number. This inhibition may be indicative of the combined effects that many different flavonoids in the apple extract have on colon cancer cells. Future research will investigate the mechanisms of action of this extract. This research was funded in part by the Michigan Apple Committee.