Food & Nutrition Research

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ISSN / EISSN : 1654-6628 / 1654-661X
Published by: SNF Swedish Nutrition Foundation (10.29219)
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Huan-Huan Zhou, Guiping Wang, Lan Luo, Wei Ding, Jia-Ying Xu, Zengli Yu, Li-Qiang Qin, Zhongxiao Wan
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.5496

Abstract:
Background: Existing evidence suggest that lactoferrin might be beneficial for Alzheimer’s disease, while precise mechanisms are not fully elucidated. Objective: To determine the effects of lactoferrin intervention on cognitive function from APPswe/PS1dE9 (APP/PS1) mice, and potential mechanisms involved. Design: Both the young and middle-aged male APP/PS1 mice were divided into the control and lactoferrin intervention groups with 16 weeks’ intervention. Results: Lactoferrin had no effects on cognitive function for both the young and middle-aged mice, and no key markers involved in Aβ, tau pathology, neuro-inflammation and synaptic plasticity were altered after lactoferrin intervention. With regards to gut microbiota profiles, in the young APP/PS1 mice, lactoferrin elevated the α diversity index including ACE and Chao 1, and reduced the relative abundance of the genera Bacteroides and Alistipes and elevated Oscillibacter; in addition, Oscillibacter, Anaerotruncus, EF096579_g, EU454405_g, Mollicutes_RF39, EU474361_g, EU774448_g, and EF096976_g were specifically abundant via linear discriminant analysis with effect size (LEfSe) analysis. In the middle-aged APP/PS1 mice, the relative abundance of the phylum Proteobacteria, as well as the genera Oscillospira, Coprococcus, and Ruminococcus was significantly reduced post lactoferrin; additionally, S24_7, Bacteroidia, Bacteroidetes, and Methylobacterium were specific via LEfSe analysis in the lactoferrin group. Conclusions: Dietary lactoferrin might be beneficial for gut microbiota homeostasis although it might have no effects on cognition.
Tatsuya Moriyama, Serina Kinugasa, Shota Hidaka, Serina Tanaka, Eri Izumi,
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.7610

Abstract:
Background: Kiwifruit is a popular fruit consumed worldwide and is also used as a cosmetic ingredient. However, it is known to cause allergic reactions in humans. Recent studies have suggested an association between food allergy and food allergens entering the body via the skin. However, percutaneously sensitizing kiwifruit allergens have not been identified in human studies or in animal models. Objective: This study aimed to identify kiwifruit proteins that percutaneously sensitized mice through the epidermal application of crude extracts from green and gold kiwifruit on the dorsal skin, and serum IgE and IgG1 levels were used as sensitization markers. Design: BALB/c mice were back-shaved and their skin was exposed to crude extracts from green and gold kiwifruit that contained sodium dodecyl sulfate. Specific IgE and IgG1 antibodies generated and secreted in response to antigens were measured using enzyme-linked immunosorbent assay or immunoblotting. Results: Skin exposure to kiwifruit extract induced an increase in the levels of kiwifruit-specific IgE and IgG1, which are helper T cell 2-related allergenic antibodies in mice. These antibodies reacted with 18, 23, and 24 kDa proteins found in both green and gold kiwifruits. Thus, three percutaneously sensitizing allergens were identified and purified. Their amino acid sequences partially matched with that of kiwellin (Act d 5). Discussion and conclusion: Kiwellin has been identified as a plant defense-related protein. Interestingly, many plant allergens are biodefense-related proteins belonging to the pathogenesis-related protein family. Kiwellin, which was discovered to be a transdermal sensitizing antigen, might also be categorized as a biodefense-related protein. This study is the first to identify kiwellin (Act d 5) as a percutaneously sensitizing kiwifruit allergen in a mouse model.
Meili Gao, Chun Deng, Fan Dang
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.3602

Abstract:
Although sorafenib (Sor) is the only effective drug for hepatocellular carcinoma (HCC), its therapeutic potential to date is mainly limited to the low tumor response. This study was designed to explore whether resveratrol (Res) could potentiate the anticancerous activity of Sor. We used HepG2 and Huh7 HCC cell lines and BALB/c nude mice for in vitro and in vivo studies, respectively. The cultured cell lines and tumor induction in the mice were treated with different concentrations of Res and Sor alone, and the combination of Res and Sor to observe the antitumor effects. Significant inhibitory effects were observed in the combined treatment of Res and Sor compared to Res and Sor alone treatments both in vitro and in vivo as demonstrated by significantly high number of S phase cells and apoptotic cells. Moreover, these findings were accompanied by the reduction of CDK2, CDC25A, PKA, p-AMPK, and eEF2K protein levels and the increment of cyclin A, cleavage caspase-3, caspase-8, and caspase-9 protein levels. The combinational treatment exhibited more significant anticancerous effect than the Res and Sor alone treatments in mice-bearing HepG2 xenograft. Overall, our results suggest that PKA/AMPK/eEF2K pathway is involved in the synergistic anticancerous activity of Res and Sor combination treatment in HCC cells. Thus, Res and Sor combination therapy may be promising in increasing the tumor response of Sor in the future.
Eli Anne Myrvoll Blomkvist, Andrew K. Wills, Sissel Heidi Helland, Elisabet Rudjord Hillesund, Nina Cecilie Øverby
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.7679

Abstract:
Background: Children’s first years of life are crucial to their future health. Studies show that a varied diet with a high intake of vegetables is positive in several domains of health. The present low vegetable intake amongst children is, therefore, a concern. Food neophobia is a common barrier to vegetable intake in children. As most Norwegian children attend kindergarten from an early age, kindergartens could contribute to the prevention of food neophobia and the promotion of vegetable intake. Objective: The aim of this study was to assess the effect of a cluster randomised trial amongst 1-year-old children in kindergarten to reduce food neophobia and promote healthy eating. Methods: Kindergartens were randomly allocated to either a control group or one of two intervention groups. Both intervention groups (diet and diet + Sapere-method) were served a warm lunch meal including three alternating intervention vegetables, whilst the intervention group 2 (diet + Sapere) in addition received tools for weekly sensory lessons. The intervention was digitally administered via information and recipes on a study website. The control group did not receive any information. Parents completed digitally distributed questionnaires addressing food neophobia and food habits at baseline and post-intervention. Results: The parents of 144 1-year-old children in 46 kindergartens completed the questionnaires, which were included in the main analysis. The results suggested a higher intake of the intervention vegetables in group 2 (diet + Sapere) compared to the control group. The effect on total vegetable intake was inconclusive. No effect was observed on the level of food neophobia in either of the intervention group. Conclusion: This digitally delivered dietary and sensory intervention promoted the intake of intervention-targeted vegetables with inconclusive effect on total vegetable intake due to large loss to follow-up. No effect on the level of food neophobia was detected.
Anne Høyer, Jacob Juel Christensen, Erik Kristoffer Arnesen, Rikke Andersen, Hanna Eneroth, Maijaliisa Erkkola, Eva Warensjö Lemming, Helle Margrete Meltzer, Þórhallur Ingi Halldórsson, Inga Þórsdóttir, et al.
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.7828

Abstract:
Background: As part of the process of updating national dietary reference values (DRVs) and food-based dietary guidelines (FBDGs), the Nordic Nutrition Recommendations 2022 project (NNR2022) will select a limited number of topics for systematic reviews (SRs). Objective: To develop and transparently describe the results of a procedure for prioritisation of topics that may be submitted for SRs in the NNR2022 project. Design: In an open call, scientists, health professionals, national food and health authorities, food manufacturers, other stakeholders and the general population in the Nordic and Baltic countries were invited to suggest SR topics. The NNR2022 Committee developed scoping reviews (ScRs) for 51 nutrients and food groups aimed at identifying potential SR topics. These ScRs included the relevant nominations from the open call. SR topics were categorised, ranked and prioritised by the NNR2022 Committee in a modified Delphi process. Existing qualified SRs were identified to omit duplication. Results: A total of 45 nominations with suggestion for more than 200 exposure–outcome pairs were received in the public call. A number of additional topics were identified in ScRs. In order to omit duplication with recently qualified SRs, we defined criteria and identified 76 qualified SRs. The NNR2022 Committee subsequently shortlisted 52 PI/ECOTSS statements, none of which overlapped with the qualified SRs. The PI/ECOTSS statements were then graded ‘High’ (n = 21), ‘Medium’ (n = 9) or ‘Low’ (n = 22) importance, and the PI/ECOTSS statements with ‘High’ were ranked in a Delphi process. The nine top prioritised PI/ECOTSS included the following exposure–outcome pairs: 1) plant protein intake in children and body growth, 2) pulses/legumes intake, and cardiovascular disease and type 2 diabetes, 3) plant protein intake in adults, and atherosclerotic/cardiovascular disease and type 2 diabetes, 4) fat quality and mental health, 5) vitamin B12 and vitamin B12 status, 6) intake of white meat (no consumption vs. high consumption and white meat replaced with red meat), and all-cause mortality, type 2 diabetes and risk factors, 7) intake of n-3 LPUFAs from supplements during pregnancy, and asthma and allergies in the offspring, 8) nuts intake and cardiovascular disease (CVD) and type 2 diabetes in adults, 9) dietary fibre intake (high vs. low) in children and bowel function. Discussion: The selection of topics for de novo SRs is central in the NNR2022 project, as the results of these SRs may cause adjustment of existing DRVs and FBDGs. That is why we have developed this extensive process for the prioritisation of SR topics. For transparency, the results of the process are reported in this publication. Conclusion: The principles and methodologies developed in the NNR2022 project may serve as a framework for national health authorities or organisations when developing national DRVs and FBDGs. This collaboration between the food and health authorities in Denmark, Estonia, Finland, Iceland, Latvia, Lithuania, Norway and Sweden represents an international effort for harmonisation and sharing of resources and competence when developing national DRVs and FBDGs.
Ping Li, Xiaoyu Chen, Tianyi Teng, Xiuqin Fan, Tiantian Tang, Rui Wang, Yurong Zhao, Kemin Qi
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.7548

Abstract:
Background: Maternal exogenous docosahexaenoic acid (DHA)-rich n-3 polyunsaturated fatty acids (PUFAs) intake during the pregnancy, especially DHA, has inconsistent effects on reducing the fat storage of the infants in different clinical studies. Objectives: We sought to determine the effects of maternal exogenous DHA-rich n-3 PUFAs capsule intake from the different pregnancy periods on the weight gain of their infants through modifying the DNA methylation status of obesity-associated genes in the umbilical cord blood. Design: A prospective 3-year follow-up study after the pregnancy was enrolled in this cohort from May to October 2016. They were divided into different groups according to the initial time of exogenous DHA capsule intake through the questionnaires (S1 – early trimester, S2 – mid-trimester, S3 – late trimester, and control – without). The concentrations and compositions of DHA were determined by gas chromatography. We applied quantitative DNA methylation states of the obesity-associated genes in the umbilical cord blood. The growth outcomes and relevant Z-scores were recorded at birth and 1 and 2 years. The correlations between DNA methylation status of the obesity-associated genes with the consents of DNA and body mass index (BMI) values were investigated as the measures. Results: In total, 205 pregnant women and their infants were eligible for this follow-up study. The concentrations and compositions of DHA in the colostrum and umbilical cord blood were higher in the S1 and S2 groups than those in the control and S3 groups as well as the decreased weight, BMI, weight for age Z-score (WAZ) and BMI for age Z-score (BMI Z) at birth and 1 and/or 2 years, and higher levels of global DNA methylation and many CpG sites in the obesity-associated genes, such as CpG2, CpG9, CpG11, and CpG16 of PPAR-γ; CpG2,3, CpG4-6, CpG8, CpG9,10, CpG11, CpG15,16, and average of CCAAT/enhancer binding protein α (C/EBP-α); CpG1 and average of adiponectin; CpG1, CpG2, CpG3, CpG5, CpG6, CpG7, and average of insulin-like growth factor 2 (IGF-2); CpG6, CpG7, CpG9, CpG16, CpG23, and CpG24 of leptin, which were more obvious in the S1 group when compared with those in the S2 group. These above hypermethylation levels of CpG sites were negatively correlated with the BMI and positively related with the changes of DHA in the colostrum and umbilical cord blood. Conclusions: Maternal exogenous DHA-rich n-3 PUFAs intake from early- and mid- trimesters of the pregnancy may avoid the development of obesity among Chinese Han infants until 2 years by modulating DNA methylation states of obesity-associated genes, which could provide attractive targets for prenatal prevention of the metabolic disorders.
Liang Wu, Yuxuan Wang, Xiaoyan Wang, Jun Liao, Hao Dong, Xiyunyi Cai, Yurong Wang, Harvest F. Gu
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.7549

Abstract:
Background: Colocasia esculenta Schott (called as Xiangshayu in Chinese) is an excellent local cultivar of the genus polymorpha in Jiangsu Province, China. Objective: In the present study, we have performed a comparative study before and after dietary consumption with Colocasia esculenta Schott to evaluate its anti-cancerous properties. Design: Forty-two healthy volunteers were recruited, and dietary consumption with 200 g of tap water cooked Colocasia esculenta Schott daily was conducted for 1 month. Plasma samples from the subjects before and after dietary consumption with Colocasia esculenta Schott were analyzed with proximity extension assays for the alteration of 92 proteins in relation with cancers, while blood samples were examined for physiological parameters with an automatic biochemical analyzer. Bioinformatic analyses were conducted using MalaCards and GEPIA. Results: After taking dietary consumption with Colocasia esculenta Schott, circulating CYR61, ANXA1, and VIM protein levels in the subjects was found to be most significantly downregulated, while for ITGB5, EPHA2, and CEACAM1, it was upregulated. Alternation of these proteins was predicted to be associated with the development of tumors such as pancreatic adenocarcinoma and breast and prostate cancers. Conclusion: The present study provides evidence that Colocasia esculenta Schott, as a healthy food, has anti-cancerous properties. Further investigation of phytochemistry in Colocasia esculenta Schott has been taken into our consideration.
Mengling Zhang, Jian Liu, Rui Zhang, Zengenni Liang, Shenghua Ding, Huanling Yu, Yang Shan
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.5649

Abstract:
Background: Hypoxia is associated with abnormal cell apoptosis in trophoblast cells, which causes fetal growth restriction and related placental pathologies. Few effective methods for the prevention and treatment of placenta-related diseases exist. Natural products and functional foods have always been a rich source of potential anti-apoptotic drugs. Nobiletin (NOB), a hexamethoxyflavonoid derived from the citrus pomace, shows an anti-apoptotic activity, which is a non-toxic constituent of dietary phytochemicals approved by the Food and Drug Administration. However, their effects on hypoxia-induced human trophoblast cells have not been fully studied. Objective: The aim of this study was to investigate the protective effects of NOB on hypoxia-induced apoptosis of human trophoblast JEG-3 and BeWo cells, and their underlying mechanisms. Design: First, the protective effect of NOB on hypoxia-induced apoptosis of JEG-3 and BeWo cells was studied. Cell viability and membrane integrity were determined by CCK-8 assay and lactate dehydrogenase activity, respectively. Real Time Quantitative PCR (RT-qPCR) and Western blot analysis were used to detect the mRNA and protein levels of HIF1α. Propidium iodide (PI)-labeled flow cytometry was used to detect cell cycle distribution. Cell apoptosis was detected by flow cytometry with Annexin V-FITC and PI double staining, and the expression of apoptosis marker protein cl-PARP was detected by Western blot analysis. Then, the molecular mechanism of NOB against apoptosis was investigated. Computer molecular docking and dynamics were used to simulate the interaction between NOB and p53 protein, and this interaction was verified in vitro by Ultraviolet and visible spectrum (UV-visible spectroscopy), fluorescence spectroscopy and circular dichroism. Furthermore, the changes in the expression of p53 signaling pathway genes and proteins were detected by RT-qPCR and Western blot analysis, respectively. Results: Hypoxia treatment resulted in a decreased cell viability and cell membrane integrity in JEG-3 and BeWo cell lines, and an increased expression of HIF1α, cell cycle arrest in the G1 phase, and massive cell apoptosis, which were alleviated after NOB treatment. Molecular docking and dynamics simulations found that NOB spontaneously bonded to human p53 protein, leading to the change of protein conformation. The intermolecular interaction between NOB and human p53 protein was further confirmed by UV-visible spectroscopy, fluorescence spectroscopy and circular dichroism. After the treatment of 100 μM NOB, a down-regulation of mRNA and protein levels of p53 and p21 and an up-regulation of BCL2/BAX mRNA and protein ratio were observed in JEG-3 cells; however, there was also a down-regulation of mRNA and protein levels observed for p53 and p21 in BeWo cells after the treatment of NOB. The BCL2/BAX ratio of BeWo cells did not change after the treatment of 100 μM NOB. Conclusion: NOB attenuated hypoxia-induced apoptosis in JEG-3 and BeWo cell lines and might be a potential functional ingredient to prevent pregnancy-related diseases caused by hypoxia-induced apoptosis. These findings would also suggest the exploration and utilization of citrus resources, and the development of citrus industry.
Lingyu Fang, Meili Zhang, Lianqiang Wu, Ruiquan Wang, Bangbang Lin, Jianfeng Yao, Dongmei Chen
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.5346

Abstract:
Background: Preterm human milk has advantages over preterm formula (PF), but it may compromise some functions after pasteurization. Objective: To explore the effects of preterm donor milk (DM) on growth, feeding tolerance, and severe morbidity in very-low-birth-weight infants. Method: This was a single-center, prospective cohort study that included 304 preterm infants weighing <1,500 g or of gestational age 0.05). Feeding intolerance in the DM group was significantly lower than that in PF group (P < 0.05), and parenteral nutrition time and hospitalization time were also shorter than that in the PF group (P < 0.05). Moreover, the incidence of necrotizing enterocolitis and sepsis was also significantly lower in the DM group (P < 0.05). Conclusion: The study indicated that preterm DM does not affect the growth of very-low-birth-weight infants. Further, it significantly reduces feeding intolerance, helps achieve full enteral feeding early, and has protective effects against necrotizing enterocolitis and sepsis. Thus, compared with formula, preterm DM can lower the rate of infection in preterm infants and is worthy of promotion.
Ursula Schwab, Maria Lankinen, Markku Laakso
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.7721

Abstract:
Purpose: Genetic and lifestyle/environmental factors as well as their interplay contribute to the pathogenesis of type 2 diabetes (T2D). Several trials have shown that lifestyle intervention is effective in the prevention of T2D, but there are no trials that have taken into account the genetic risk of the participants. The aim of our T2D-GENE trial (ClinicalTrials.gov ID: NCT02709057) is to investigate the effects of lifestyle intervention on the prevention of T2D in participants with a high genetic risk of T2D compared with participants with a low genetic risk of T2D. Methods: Both intervention and control groups include 300 participants with low and 300 participants with high genetic risk for T2D. Genetic risk was evaluated by genetic risk score, and these two groups were matched additionally for fasting plasma glucose concentration, age, and body mass index. Corresponding control groups (300 participants each) do not have lifestyle intervention. The inclusion criteria are impaired fasting glucose at entry with or without impaired glucose tolerance, age 50–75 years, and body mass index ≥25 kg/m2. The primary outcome is incident T2D and the intervention lasts for 3 years. Conclusion: If the effects of the lifestyle intervention are independent from the genetic risk of the participants, our study will be of great importance for the entire T2D research community, health care providers, and individuals at high risk for T2D. In this case, lifestyle intervention is beneficial for all individuals at risk for developing T2D, independently of genetic risk.
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