bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term efficacy of a refreshing beverage, fortified with selected micronutrients, to improve the micronutrient status of schoolchildren and women in the context of the nutritional situation in rural Guatemala
Authors: Oliva Raquel Campos , Soto‐Méndez María José , Solomons Noel W. , Armas Laura , Selhub Jacob , Paul Ligi , Kraemer Klaus 
Published: November 2023

BackgroundNutritive beverages can be important sources of micronutrients. There is a need and an opportunity to determine how beverages can play their most healthful and nutritionally‐relevant role in the diets of rural populations at risk of nutrient deficiencies.ObjectiveTo compare the evolution of biomarkers of nutritional status with respect to four vitamins (riboflavin, folate, vitamins B12 and D), across two rural samples (schoolchildren and women of fertile age), randomized to receive supervised consumption of a daily serving of a beverage.MethodsA total of 236 women, and 156 schoolchildren of both sexes in 12 villages. All with informed consent, were enrolled in the baseline sampling of blood for circulating concentrations of riboflavin, folate, vitamins B12 and D in March, 2011. As of May, 2011, 10‐month, household‐level, stratified‐randomization intervention commenced, distributing 350 mL bottles of a fortified or non‐fortified beverage available to participants. Nutritional evaluation was repeated at the endline in March 2012 in the same individuals.ResultsImportant differential (baseline‐to‐endline) increases, contrasting between fortification and non‐fortification groups, existed for children with riboflavin (+16.4 vs +5%), vitamin B12 (+33.9 vs +6.5%) and vitamin D (+23.3% vs +5.0%), but not for folate. The corresponding analysis for adult women revealed an effect for folate (+30.4 vs +11.5%), but not for the remaining vitamins. All children were folate adequate at all stages. Differentially greater endline adequacy of biomarker status was seen in the fortification vs non‐fortification groups for riboflavin (25.5% vs 6.5%), vitamin B12 (46.2% vs 6.2%) and vitamin D (41.0 vs 8.6%). For women and folate, the two treatment groups had 92.3 vs 43.7% reaching normal levels at endline. Among the other three vitamins, only up to a third of women had normal status at endline without a treatment‐wise effect.ConclusionIncreases in circulating biomarkers occurred for most nutrients, variously among adult women and children, but complete resolution of initial low‐vitamin status was not seen for any nutrient.Support or Funding Informationcbc, Guatemala; DSM Nutritional and Sight & Life, Basel, Switzerland
Impact of Vitamin C supplementation on Risk for Cardiovascular events: future scenario for the elderly US population
Authors: Vecchio Maria Gabriella , Minto Clara , Gregori Dario 
Published: November 2023

BackgroundMicronutrients are an essential component in nutrition, ensuring the maintenance of a good state of health. Nowadays, among the global population, there is a high consumption of food supplementation in particular for what concern micronutrients. Several studies demonstrated that vitamins (i.e Folic acid, Vitamin C, β‐carotene), due to their intrinsic properties, have a proven efficacy toward a series of potential health targets. The aim of this study was to produce an estimation of the public health impact that vitamin supplementations have in terms of cardiovascular events risk reduction on the U.S. elderly population over the next 10 years.MethodsRelevant articles published until September 2014 were collected using electronic database PubMed. The search string was “vitamins”, limited to “clinical trials or cohort studies” and “humans”. 18091 records were retrieved and screened. Selected papers entered the meta‐analysis for effects of micronutrients. A random‐effect Der‐Simonian Laird model was estimated for the risk of having any cardiovascular event in cases of supplementation (irrespectively of dosage) or no supplementation. Dose‐response curve has been estimated using a over‐dispersed binomial meta‐regression model. Scenarios have been extrapolated to US via stochastic simulations (10000 Monte Carlo runs).ResultsNo significant reduction of Cardiovascular Events (CE) risk was found for Folic Acid (OR 0.97, 95% CI 0.91 – 1.02), β‐Carotene (OR 1.01, 95% CI 0.96 – 1.05) and Vitamin C (OR 1.03, 95% CI 0.95 – 1.11), irrespectively from dose. Only for Vitamin C, reduction in risk is significantly associated with dose of supplementation higher than 400 mg/day.ConclusionIn USA, more than 40 million people are older than 65 years. The figures increased from 2000 to 2010 census by 5276231 people. Assuming a steady growth also in the forthcoming years, a wide adoption of Vitamin C supplementation in adult and elderly population of 400mg/day could be associated in avoiding approximately additional 377670 (95% CI 256450 – 459998) CE in the forthcoming 10 years.

Cardiovascular events risk and vitamin supplementation

Vitamin
Dose (mg/day)
OR for CE
95% CI

Vitamin C
400
0.93
(0.88, 0.99)

β‐Carotene
50
0.28
(0.03, 3.00)

Folic Acid
2000
21.20
(0.01, 60.11)
Effect of thymol on oxidative stress and inflammation‐related gene expression in high fat diet‐induced hyperlipidemic rabbits
Authors: Yu Ya‐Mei , Chao Tzu‐Yu , Chang Weng‐Cheng , Chang Margaret J. , Lee Ming‐Fen 
Published: November 2023

Cardiovascular diseases contribute to one major cause of deaths worldwide, where atherosclerosis plays a key role in the development of the diseases and is often associated with oxidative stress and local inflammation. Thymol, a polyphenolic compound in thyme which has been widely used in cooking, food preservation, and folk medicine, exhibits both antioxidant and anti‐inflammatory properties. This study was aimed to investigate the effect of thymol in a high fat diet‐induced hyperlipidemic animal model. New Zealand white rabbits were fed with regular chow, high fat and cholesterol diet (HC), T3 or T6 (HC supplemented with thymol at 3 or 6 mg/kg/day), for 8 weeks. Aortic intimal lipid lesion, serum lipid profiles, inflammation‐related biomarkers including C‐reactive protein (CRP), interleukin‐1 (IL‐1)β, IL‐6, tumor necrosis factor (TNF)‐α, TNF‐β, and atherosclerosis‐associated indicators including vascular cell adhesion molecule‐1 (VCAM‐1), monocyte chemotactic protein‐1 (MCP)‐1, and matrix metalloproteinase (MMP)‐9, were significantly increased in the HC group but lessened upon thymol supplementation. Our data indicate that thymol not only displays strong antioxidant activity but also reduces aortic intimal thickness, lower serum lipids and oxidative stress, and alleviate inflammatory reactions, thereby may suppress the development of high fat diet‐induced hyperlipidemia and atherosclerosis.Support or Funding InformationThis study was supported by NSC102‐2320‐B‐309‐001‐MY3 to M‐F Lee and NSC99‐2320‐B‐309‐002 to Y‐M Yu.
The Effects Of Soluble Dietary Fiber On Blood Pressure: A Systematic Review And Meta Analysis Of Randomized Controlled Trials
Authors: Jovanovski Elena , Khan Kashif , Sievenpiper John , Ho Thanh , Zurbau Andreea , Au‐Young Rodney , Mejia Sonia Blanco , Vuksan Vladimir 
Published: November 2023

ObjectiveEpidemiological evidence suggests an inverse relationship between soluble fiber intake and blood pressure, while evidence from randomized controlled trials remains largely controversial and poorly characterized. The present study aim is to conduct a systematic review and a meta‐analysis of randomly controlled trials to assess the effects of soluble fiber intake on blood pressure.Study DesignMedline, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials, through to January 2015 were searched. Randomized, controlled, clinical trials that were ≥30 days in duration testing soluble fiber supplementation against an adequate comparator were included. Two independent reviewers extracted the data and assessed study quality and risk of bias. Data were pooled using the generic inverse variance method with random effects model and were expressed as mean differences (MD) with 95% confidence intervals (CI). Study heterogeneity was estimated using Cochran Q‐statistic and quantified I2 statistic. Studies were also assessed for their quality using the Heyland Methodological Quality Score and for risk of bias using Cochrane's risk of bias tool.ResultsFourteen studies (n=1112 participants) were included for analysis. Soluble fiber had no effect on systolic (MD=1.00 mmHg [95% CI 2.46 to 0.46]) or diastolic (MD=L0.23 mmHg [95% CI 1.17, 0.71]) blood pressures. Substantial and moderate unexplained heterogeneity were present for the systolic (I2=63%, P=0.18) and diastolic (I2=40%, P=0.63) blood pressure analyses.ConclusionPooled analyses show that dietary supplementation of soluble fiber from all sources is not associated with systolic or diastolic blood pressure reduction. More studies will need to be included in future meta analyses to better understand the potential blood pressure reducing effects of soluble fiber, especially in patients with hypertension, and to delineate potential benefits of highly viscous soluble fibers.Support or Funding InformationSupported by Internal research funding.
Enhancement the Antioxidant Activity, Total Phenolic and Flavonoid Contents by Optimizing the Germination Conditions of Desi Chickpea (Cicer arietinum L) Seeds
Authors: Domínguez Dulce , Cuevas Edith , Milan Jorge , Garzón Jose Antonio , Canizalez Adrian , Gutirerrez Roberto , Rochin Saraid Mora , Reyes Cuauhtemoc 
Published: November 2023

Legumes have high nutritional value and play an important role in traditional diets throughout the world. Consumption of legumes has been linked to reduced risk of diabetes and obesity, coronary heart disease, colon cancer, prostate cancer, and gastrointestinal disorders. Some biotechnological processes such as germination are considered both simple and economical to improve the nutritive and functional value of legumes due to the increase in the bioactive compounds and related antioxidant acitivity. Chickpea (Cicer arietinum L.) is one of the most important grain‐legume crops in the world. Chickpeas contain high levels of proteins, carbohydrates, minerals, vitamins, unsaturated fatty as well as bioactive compounds.The aim of this study was to optimize the germination conditions of desi chickpea seeds that would maximize the antioxidant activity (AoxA), total phenolic (TPC), and flavonoid (TFC) contents. To optimize the germination bioprocess, response surface methodology was applied over three response variables (AoxA, TPC, TFC). A central composite rotable experimental design with two factors [germination temperature (GT), 20–35ºC; germination time (Gt), 10–240 h] in five levels was used; 13 treatments were generated. The sprouts from each treatment were lyophilized, tempered, and ground to obtain germinated chickpea flours (GCF). The best combination of germination bioprocess variables for producing optimized GCF with the highest AoxA [ABTS: 14,435 □mol Trolox equivalents (TE) / 100 g simple, dw; ORAC: 15,143 □mol TE/100 g sample, dw], TPC [217.69 mg Gallic acid equivalents (GAE) / 100 g sample, dw], and TFC [122.61 mg Quercetin equivalents (QE)/100 g sample, dw] was GT= 34ºC/Gt=171 h. The germination bioprocess increased AoxA, TPC, and TFC in 146–178, 98, and 111 %, respectively. The germination is an effective strategy to increase the TPC and TFC of desi chickpea seeds for enhancing functionality with improved antioxidant activity. The chickpea germinated flour or extract might be recommended for use as a source of natural antioxidants in functional foods.Domínguez‐Arispuro DM1, Cuevas‐Rodríguez EO1,2, Milán‐Carrillo JM1,2, Garzón‐Tiznado JA1, Canizalez‐Roman VA1, Gutiérrez‐Dorado R1,2, Reyes‐Moreno C1,2*1 Programa Regional de Posgrado en Biotecnología, Facultad de Ciencias Químico Biológicas (FCQB), Universidad Autónoma de Sinaloa (UAS), Ciudad Universitaria, AP 1354, CP 80,000 Culiacán, Sinaloa, México.2 Programa de Posgrado en Ciencia y Tecnología de Alimentos, FCQB‐UAS, Cd Universitaria, AP 1354, CP 80,000 Culiacán, Sinaloa, México.(*) C Reyes‐Moreno, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Calle Lichis Ote 1986, Col La Campiña, CP 80,060 Culiacán, Sinaloa, México, e mail: creyes@uas.edu.mx
Cytotoxic effect of proanthocyanidins from a Mexican endemic blackberry (Rubus liebmannii) on the synthesis of ROS on two murine glioma cell lines
Authors: Cuevas‐Rodríguez Edith‐Oliva , Sanchez‐Velazquez Oscar‐Abel , Rangel‐Lopez Edgar , Saraid Mora‐Rochin , Reyes‐Moreno Cuauhtemoc , Milan‐Carrillo Jorge 
Published: November 2023

Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism as well as in cellular response to xenobiotics, cytokines, and bacterial invasion, and it indicates possible cellular damage. In tumor cells the accelerated metabolism produces a high number of ROS. Brain tumors represent the third cause of death in cancer patient's woldwide. Gliomas are the most frequents tumors of the neuroepitelial tissue, and they are graded on a scale from I to IV based on their malignancy. The alternative medicine offers some options of natural origin as possible therapeutic agents against neoplastic cells, such as proanthocyanidins extracted from berries and other fruits and grains. Here, the objective was to determine the cytotoxic effect of proanthocyanidins from a wild blackberry (R. liebmanii) from Mexico on two murine glioma cell lines (C6 and RG2), and determinate the formation of ROS. After 22 and 46 hours of incubation (1 × 105 cells/mL) at 37°C, the viability was determined with two concentrations of proanthocyanidins (0.5 y 100 μg/mL) extracts by 24 and 48 h, respectively, in 96 well plates. ROS concentration was determined with spectrophometric method using 2′,7′‐DCFH‐diacetate (DCFH‐DA). Our results show that the neoplastic cells has a dose dependent cytotoxic response and the major effect was at 48 hours of exposition at 100 μg/mL in RG2 (>80%) vs the control. The results obtained will allow us to suggest suitable compounds for the development of alternative treatment against tumors of glial origin.Support or Funding InformationPROFAPI2014, Universidad Autonoma de Sinaloa, Mexico
Preparation technology of feruloylated fatty acyl structured lipids and its stabilities in high temperature
Authors: Wang Qiang , Long Jie , Zhang Yubin 
Published: November 2023

Ferulic acid has obvious antioxidant, scavenging free radicals, anti infection and neuroprotective effects. However, the poor solubility of ferulic acid, which limits its application in the oil based food, medicine, and cosmetics. Several studies have found that the natural antioxidant composition of the modified structure of lipid can significantly improve the application of natural antioxidant components. To model and optimize the reaction conditions of enzymatic esterification of ferulic acid with maize germ oil in solvent system by response surface metodology (RSM) based commercial lipases Lipozyme RM IM. Central composite design was used to design the experiments. The reaction factors investigated were the substrate molar ratio of maize germ oil and ferulic acid (Sr=4:1~10:1), temperature (T=60~80°C) and time (t=20~30h). The yield of of eruloylated fatty acyl structured lipids was selected as response value. All factors investigated positively affected the yield of of eruloylated fatty acyl structured lipids. The optimal reaction conditions were: Sr =8.9, T=76.0°C and t=28.1h, and yield of of eruloylated fatty acyl structured lipids was 59.1% under these conditions. The actual value was in reasonable agreement with the predicted value of 58.8%. The above prepared structured lipids produces low polymer in the frying experiment, and it has high storage stability. RM IM Lipozyme is an effective and specific technique for the synthesis of ferulic acyl fatty acyl group. It can be used in the produced process of feruloylated fatty acyl structured lipids.Support or Funding InformationThis research was supported by the Natural Science Foundations of China (No. 31401559)
Salt Exacerbates Development of Aortic Dissection and Rupture in LNK/SH2B3 Deficient Mice
Authors: LAROUMANIE Fanny , Saleh Mohamed A. , McMaster William , Kirabo Annet , Madhur Meenakshi s. 
Published: November 2023

BackgroundInflammation plays a key role in the development of aortic dissection. In particular, the Th1 cytokine IFNγ has been detected in patients with aortic dissection. A polymorphism in the gene SH2B3 encoding the lymphocyte adaptor protein, LNK, is associated with hypertension and other cardiovascular and autoimmune diseases in human. We previously showed that mice deficient in LNK have exacerbated hypertension, enhanced T cell production of IFNγ and increased aortic inflammation. Salt has been shown to modulate T cell polarization. We hypothesized that LNK deficiency promotes aortic dissection/rupture at least in part through enhanced production of IFNγ, and that this is exacerbated by salt.MethodsLNK−/− mice or wild type (WT) controls were infused with angiotensin II (1000 ng/kg/min) for 14 days with or without an initial intraperitoneal injection of saline equal to 10% of their body weight. Kaplan‐Meier survival curves were generated and flow cytometry, histology, and quantitative RT‐PCR were employed to evaluate aortic inflammation, remodeling, and gene expression.ResultsLNK−/− mice infused with angiotensin II exhibited an accelerated rate of suprarenal aortic dissection or rupture compared to WT mice, and this was exacerbated by salt injection (Figure). Aortas from LNK−/− mice treated with salt plus angiotensin II expressed higher mRNA levels of IFNγ (2.8 fold increase, p<0.05) and the Th1 transcription factor T‐bet (6.2 fold increase, p<0.05) compared to aortas from WT mice that underwent the same treatment. Moreover, the aortic expression of the metalloproteinase MMP‐9 was upregulated compared to WT mice. In mice that developed aortic rupture, loss of LNK was associated with a decrease in the aortic expression of both pro collagens type 1 and 3.ConclusionLoss of LNK combined with salt exacerbates the development of aortic dissection and rupture. Targeting LNK and reducing salt intake may be a potential therapeutic strategy for the management of aortic dissections.Support or Funding InformationThe Fondation pour la Recherche Medicale (FRM)
Intronic regulation of human GLI1 DNA by cis DNA elements and epigenetic marks
Authors: Iannaccone Philip , Taylor Robert , Long Jun , Childs Ronnie , Yoon JoonWon , Sylvestersen Kathrine , Nielsen Michael Lund , Walterhouse David O. , Robbins David 
Published: November 2023

In humans, a large cancer burden is associated with dysregulation of the Hedgehog/Patched/GLI (HH/PCTH/GLI) pathway. The canonical Hedgehog signal (including Sonic Hedgehog [SHH]) is mediated by the GLI family of transcription factors (GLI1, GLI2 and GLI3). GLI1 plays an important role in normal development and differentiation and is a human oncogene that is believed to be active in up to one‐third of all cancers. GLI1 gene targets sustain proliferation, inhibit apoptosis, and promote angiogenesis and tumor cell migration. Wild‐type p53 competes with GLI1 for the co‐activator TAF9, inhibiting GLI1's oncogenic activity. GLI1 and GLI2 form a positive‐feedback loop that drives their expression. Mechanisms that regulate this positive‐feedback loop remain unknown. We identified 6 GLI binding sites (GBS) in the large first intron of the human GLI1 gene that are highly conserved among mammals and are associated with histone H3K27Ac marks and DNase hypersensitivity clusters. GLI1 binds all of the GBS and GLI2 binds 2 of them, shown using gel mobility shift assays. Elimination of some of the GBS attenuates transcriptional activation. Removal of all GBS eliminates reporter gene activation. Preliminary evidence suggests GLI1 multimerizes and can bind the pioneer protein CBP. ChIP qPCR shows SHH signal dependent (Smoothened agonist) occupancy of the 1st intron near the GBS by GLI2, and increased occupancy by the histones H3K4me3 and H3K27Ac and the histone bromodomain reader protein BRD4. BRD4 can be driven off the intron and transcription start site region with a small inhibitory molecule, I‐BET151, providing a possible route to disrupting GLI1 expression. Further, GLI1 binds the histone variant H2A.Z. These results suggest that GLI1 and GLI2 could auto‐regulate GLI1 expression at GBS in the 1st intron of GLI1 through protein‐protein interactions involving complexes of the transcription factors, histone variants, and reader proteins. Given the widespread involvement of GLI1 and GLI2 in human cancers including medulloblastoma and rhabdomyosarcoma, it is important to try and understand key elements of the regulation of their expression.Support or Funding InformationSupported in part by PHS grant ES1054, Illinois Excellence in Academic Medicine award, Illinois Regenerative Medicine Institute and the Eisenberg Foundation for Charities.
Use of Hepatic Gene Expression Analysis to Investigate Iron Accumulation in Rats Treated with an RGMc Antagonist Monoclonal Antibody
Authors: Liguori Michael J. , Boeser Preethne , Fan Leimin , Huang Lili , Seemann Dietmar , Blomme Eric A.G. , Popp Andreas , Mueller Bernhard K. 
Published: November 2023

As the development processes mature for large molecule biologics, additional technologies to assess potential safety issues would be favorable, especially as related to target engagement. ABT‐207 is a humanized antibody that inhibits repulsive guidance molecule C (RGMc). The antibody has possible application to treat anemia of chronic disease. In this study, we used an affinity maturated variant of ABT‐207 (PR‐1285929; h5F9‐AM8) to examine the toxicological effects of RGMc inhibition. We applied hepatic whole genome transcriptomic profiling using the Affymetrix platform to investigate the effects of PR‐1285929 and to examine whether there were toxicologically relevant pathway perturbations. Female Sprague Dawley rats were treated for 3 weeks (i.v.) with PR‐1285929 at doses of 0.02, 0.20, 2.0, or 20.0 mg/kg/week. At the end of the dosing period, the rats were sacrificed, and liver was collected for histology and gene expression analysis (rat RAE230 2.0 array). Histological examination showed mild to moderate dose dependent accumulation of hepatic iron as determined by Prussian blue staining. This effect was histopathologically assessed as non‐adverse since no other effects (e.g. inflammation or degeneration) were observed. Global gene expression profiling revealed a relatively minor impact on the hepatic transcriptome. Levels of hepatic hepcidin (Hamp) mRNA, the main regulator of serum iron homeostasis, declined in excess of 20‐fold in a dose dependent manner. This finding was also reflected in liver Hamp mRNA expression as measured using RT‐PCR and decreased serum hepcidin protein levels. Interestingly, RGMc is a main regulator of hepcidin, and thus, its inhibition is likely associated with the reduced Hamp. At the transcript level, a minor oxidative stress response induction, mostly related to glutathione metabolism, was apparent at the highest dose (20 mg/kg), but lower doses revealed few consistent changes in these genes. Only minor modulations were apparent with respect to select BMPs and ferroportin. No other toxicologically relevant pathways were consistently up‐ or down‐regulated. This experimental example shows the potential utility of transcriptomic profiling to investigate plausible mechanisms of cellular changes mediated by biologic therapies and can serve as a method for risk mitigation in the development of protein pharmaceuticals.Support or Funding InformationAuthor Disclosures: All authors are employees of AbbVie. The design, study conduct, and financial support for this research was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.