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Jaeyong Kim, Gyuok Lee, Huwon Kang, Ji-Seok Yoo, Yongnam Lee, Hak-Sung Lee, Chul-Yung Choi
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.7666

Abstract:
Background: Inflammation is emerging as a key contributor to many vascular diseases and furthermore plays a major role in autoimmune diseases, arthritis, allergic reactions, and cancer. Lipopolysaccharide (LPS), which is a component constituting the outer membrane of Gram-negative bacteria, is commonly used for an inflammatory stimuli to mimic inflammatory diseases. Nuclear factor-kappa B (NF-κB) is a transcription factor and regulates gene expression particularly related to the inflammatory process. Stauntonia hexaphylla (Lardizabalaceae) is widely used as a traditional herbal medicine for rheumatism and osteoporosis and as an analgesic, sedative, and diuretic in Korea, Japan, and China. Objective: The purpose of this study was to investigate the anti-inflammatory activity of YRA-1909, the leaf aqueous extract of Stauntonia hexaphylla using LPS-activated rat peritoneal macrophages and rodent inflammation models. Results: YRA-1909 inhibited the LPS-induced nitric oxide (NO) and proinflammatory cytokine production in rat peritoneal macrophages without causing cytotoxicity and reduced inducible NO synthase and prostaglandin E2 levels without affecting the cyclooxygenase-2 expression. YRA-1909 also prevented the LPS-stimulated Akt and NF-κB phosphorylation and reduced the carrageenan-induced hind paw edema, xylene-induced ear edema, acetic acid-induced vascular permeation, and cotton pellet-induced granuloma formation in a dose-dependent manner in mice and rats. Conclusions: S. hexaphylla leaf extract YRA-1909 had anti-inflammatory activity in vitro and in vivo that involves modulation of Akt/NF-κB signaling. Thus, YRA-1909 is safe and effective for the treatment of inflammation.
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.
Núria Roglans, Miguel Baena, Gemma Sangüesa, Ana Magdalena Velázquez, Christian Griñán-Ferré, Mercè Pallàs, Rosa María Sánchez, Marta Alegret, Juan Carlos Laguna-Egea
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.7670

Abstract:
Background: Non-alcoholic fatty liver disease (NAFLD) has increased over the last decades and may evolve into hepatocellular carcinoma (HCC). As HCC is challenging to treat, knowledge on the modifiable risk factors for NAFLD/HCC (e.g. hyper caloric diets rich in fructose) is essential. Objective and design: We used a model of diethyl nitrosamine-induced hepatocarcinogenesis to investigate the liver cancer-promoting effects of a diet supplemented with 10% liquid fructose, administered to male and female rats for 11 months. A subset of the fructose-supplemented rats received resveratrol (RVT) in the last 4 months of treatment. Results and discussion: Rat livers showed no de visu or histological evidence of liver tumorigenesis. However, we observed metabolic abnormalities that could be related to cancer development mainly in the female fructose-supplemented rats, such as increases in weight, adiposity and hepatic triglyceride levels, as well as hyperglycaemia, hyperuricemia, hyperleptinemia and a reduced insulin sensitivity index, which were partially reversed by RVT. Therefore, we performed a targeted analysis of 84 cancer-related genes in the female liver samples, which revealed expression changes associated with cancer-related pathways. Analysis of individual genes indicated that some changes increased the risk of hepatocarcinogenesis (Sfrp2, Ccl5, Socs3, and Gstp1), while others exerted a protective/preventive effect (Bcl2 and Cdh1). Conclusion: Our data clearly demonstrate that chronic fructose supplementation, as the sole dietary intervention, does not cause HCC development in rats.
Kuang-Mao Chiang, Wen-Harn Pan
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.6300

Abstract:
Background: Obesity control and prevention remains challenging. Randomized controlled trials in western countries have demonstrated efficacy of dairy supplementation on fat mass reduction and lean mass increase, when combined with energy restriction protocols. However, there is scanty information on this issue among the East Asian population. Objective: The aim of this study is to investigate the association between milk consumption and weight status in Asian. Design: First, we studied the association between milk intake and body mass index (BMI) changes in a 10-year longitudinal study of Cardiovascular Disease Risk Factor Two-township Study (CVDFACTS) with 1,644 adults. Second, taking advantage of the genetic and phenotype data of 10,000 participants collected by Taiwan Biobank (TWB), we carried out a Mendelian randomization (MR) study to investigate the causal relationship between milk intake and BMI. A lactase persistence genetic marker (rs4954490) was used as the instrumental variable. Results: We found in the longitudinal study that higher baseline milk consumption level was associated with lower odds of increasing BMI or maintaining overweight/obesity status. In the MR study, we found that G allele of the rs4954490, a surrogate of greater milk intake, was associated with lower odds of being obese (BMI > 27 kg/m2); the odds ratio (OR) for the GG versus AA is 0.85 (P = 0.037), and the OR for the GA versus AA is 0.84 (P = 0.032). Conclusions: These findings support current food guide in Asian countries to include dairy group as one of the six food groups for nutrition recommendation.
Gil Zandani, Sarit Anavi-Cohen, Noa Sela, Abraham Nyska, Zecharia Madar
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.7631

Abstract:
Background: Nonalcoholic fatty-liver disease (NAFLD) is a global health problem associated with gut dysbiosis and intestinal permeability. Broccoli is a natural source of bioactive phytochemicals, characterized by health-promoting properties. Objective: This study evaluated the effect of broccoli florets and stalks on liver fat accumulation, inflammation, gut microbiome, and intestinal barrier integrity. Design: Male C57BL/6J mice (n = 32, 8-week-old) were fed with a high-fat high-cholesterol diet (HFCD) with/without 15% broccoli (florets or stalks) for 7 weeks. Liver damage was evaluated by changes in glucose response and histological and biochemical parameters. Protein and gene expressions related to liver inflammation were examined. The effect of broccoli on microbiota population together with genes related to barrier integrity in the gut was investigated. Results: Dietary broccoli improved the glycemic response assessed by oral glucose tolerance test (OGTT). Histological evaluation showed no change in hepatic steatosis. Broccoli consumption also attenuated inflammation as revealed by lower inducible nitric oxide synthase (iNOS) and serum amyloid A1 (SAA1) expression levels in broccoli-supplemented groups. Gut microbiota analysis demonstrated elevated Acidifaciens and reduced Mucispirillum schaedleri abundance in the stalks group, whereas Proteobacteria strains abundance was increased in the florets group. Gut integrity remained unchanged. Conclusion: Broccoli supplementation improves glucose tolerance, attenuates liver inflammation, and alters microbial composition, but does not affect gut integrity. This research provides new evidence on the effects of dietary broccoli under HFCD.
Suvara K. Wattanapitayakul, Khwandow Kunchana, Wattanased Jarisarapurin, Linda Chularojmontri
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.7807

Abstract:
Background: High consumption of antioxidant-rich fruits and vegetables reduces the endothelial damage involved in cardiovascular disease pathogenesis. Objective: To evaluate the phytochemical content, antioxidant and scavenging activities (FRAP, ORAC, OH•, HOCl, H2O2, and O2−), endothelial H2O2-cytoprotective effect, nitric oxide (NO) release activation potential, and endothelial wound healing properties of 10 tropical fruits, comprising pineapple, sugar apple, papaya fruit, longan, mangosteen, lychee, langsat, mango, rambutan, and guava. Design: Experimental study. The experiments were conducted in vitro using endothelial cell line EA.hy926. Results: The high performance liquid chromatography (HPLC) phytochemical analysis indicated the presence of gallic acid and quercetin in all fruits, along with the overall absence of ellagic acid. Chlorogenic acid was only detected in three fruits, that is, pineapple, ripe papaya, and guava. The antioxidant and scavenging activities of all fruits were concentration-dependent. Only the H2O2 scavenging activity exhibited broad positive associations with other ROS-scavenging activities. Sugar apple and unripe papaya induced a significant reduction in H2O2-induced cell death in endothelial cells while pineapple, sugar apple, longan, and langsat activated NO release. Discussion: All the studied tropical fruits contained bioactive phytoantioxidants with wide ranges of antioxidant capacity and scavenging activities. The endothelial functional tests were relevant to the screening for fruits that may benefit cardiovascular health. Among the four fruits that promoted endothelial wound closure, only sugar apple and unripe papaya induced cell migration and vascular capillary-like tube formation. Conclusion: Sugar apple and unripe papaya are potential functional fruits that can protect against oxidative cell death and enhance endothelial wound healing.
Jing Duan, Hua Guo, Yulin Fang, GuangBiao Zhou
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.6507

Abstract:
Background: Wine is one of the oldest and most popular drinks worldwide, which is rich in phenolic compounds. Epidemiological studies show that moderate consumption of wine can reduce the risk of certain diseases, and this effect is attributed to its phenolic compounds. Objective: The objective of this review was to elaborate the effects of wine-derived phenolic compounds for preclinical anticancer therapeutics and their major mechanisms. Methods: In this review, we discuss the classification and content of common phenolic compounds in wine and summarize previous studies that have evaluated the anticancer properties of wine-derived phenolic compounds and their mechanisms. Results: Wine-derived phenolic compounds have been proven to participate in several mechanisms against cancers, including deoxyribonucleic acid damage, oxidative stress, cell proliferation, cell cycle arrest, cell apoptosis, autophagy, cell invasion and metastasis, immunity and metabolism, regulation of multiple signaling molecules, and gene expression. However, the exact anticancer mechanisms of the phenolic compounds in wine need to be further investigated. Conclusion: Wine-derived phenolic compounds are promising chemoprotective and chemotherapeutic agents for cancer.
Gengdong Chen, Yan Li, Shujun Liang, Jinqiu Xiao, Xinyu Duan, Yuntao Zhou, Yangqing Zeng, Fanyiwen Sun, Shiksha Shrestha, Zheqing Zhang
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.4428

Abstract:
Background: Previous animal and in vitro studies indicated that anthocyanidins might contribute to the prevention of obesity, while epidemiological evidences were scarce and had not been conducted in children. Objective: We explored the associations between anthocyanidins and body composition in children. Design: A cross-sectional study involving 452 children aged 6–9 years in Guangzhou, China, was carried out. Dietary information was collected using a 79-items food frequency questionnaire. Fat mass (FM), lean mass (LM), and fat mass percentage (FMP) at multi-sites (whole body, trunk, limbs, android area, and gynoid area) were measured using a dual-energy X-ray scan. Abdominal obesity was defined as an age- and sex-specific abdominal FM ≥ 85th percentile. Handgrip strength was measured using a hydraulic hand dynamometer. Results: After adjusted for several potential covariates, higher dietary intake of anthocyanidin (per one standard deviation increase) was associated with a 0.013–0.223 kg increase of LM, a 0.024–0.134 kg decrease of FM, and a 0.63–0.76% decrease of FMP at multi-sites (P < 0.05). Results were similar and more pronounced for delphinidin and cyanidin, but less significant for peonidin. Higher dietary anthocyanidin intake (per standard deviation increase) was associated with a 41.0% (OR: 0.59, 95%CI: 0.37, 0.94) decreased risk of abdominal obesity. However, no significant associations were observed between anthocyanidin and handgrip strengths. Conclusions: Higher dietary intake of anthocyanidin and its components tended to be associated with better body composition, but not handgrip strength, in Chinese children at early age.
Chi Zhang, Chang Ge, Junsheng Wang, Dong Sun
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.7842

Abstract:
Background: Lupus nephritis (LN) is one of the most severe organ that damages the systemic lupus erythematosus (SLE). Cyclophosphamide is one of the main drugs used in the treatment of LN. Fish oil is a general term of all the oily substances in fish, whose main component is omega-3 fatty acid. This study aimed to investigate whether fish oil could be used as an adjunct to low-dose cyclophosphamide in proliferative LN treatment. Methods: A total of 237 patients with proliferative LN were recruited and randomized into two groups: cyclophosphamide + placebo group and cyclophosphamide + fish oil group. In the cyclophosphamide + placebo group, participants received prednisone + cyclophosphamide + placebo. In the cyclophosphamide + fish oil group, participants received prednisone + cyclophosphamide + fish oil. Before and after treatment, the clinical parameters of the patients in both groups were evaluated. Results: In the cyclophosphamide + fish oil group, the number of patients achieving complete remission (n = 45, 46.9%) was significantly higher than the cyclophosphamide + placebo group (n = 31, 32.6%). The number of patients achieving no response in the cyclophosphamide + fish oil group (n = 8, 8.3%) was significantly lower than the cyclophosphamide + placebo group (n = 22, 23.2%). Hematuria (P = 0.036), urine protein-creatinine ratio (uPCR) (P = 0.014), estimated glomerular filtration rate (eGFR) (P = 0.027), and renal SLE disease activity index (SLEDAI) (P = 0.009) improved more significantly in the cyclophosphamide + fish oil group. The number of patients with infection (P = 0.04) or urinary tract infection (P = 0.04) in the cyclophosphamide + fish oil group was lower than the cyclophosphamide + placebo group. Conclusion: In conclusion, the treatment of fish oil in LN patients enhances the efficiency of cyclophosphamide, alleviates nephritis-related parameters, and inhibits infection and urinary tract infection during the treatment. Thus, fish oil may serve as a potential adjuvant drug in the treatment of LN.
Korrie Pol,
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.6254

Abstract:
Background: Diets inducing high fluctuations in plasma glucose levels are linked to type 2 diabetes. L-arabinose and D-xylose have been hypothesized to inhibit intestinal sucrase activity, delay sucrose digestion, and reduce glycaemic and insulinaemic responses. However, few human studies have assessed this using realistic foods. Objective: We investigated the effects of the addition of L-arabinose and D-xylose on glucose homeostasis using a fruit-based drink and the effect of L-arabinose using a muffin. Design: Fifteen males participated in two double-blind, randomized cross-over experiments. In experiment A, three drinks were tested: (1) L-arabinose, (2) D-xylose and (3) control drink. In experiment B, two muffins were tested: (1) L-arabinose and (2) control muffin. All products consisted of ~50 g available carbohydrates, and L-arabinose or D-xylose was added as 10% of sucrose. Pre- and post-ingestive plasma glucose and insulin levels were measured at fixed time points up to 180 min after consumption. Results: Glucose and insulin peaks were lower after the L-arabinose and D-xylose drink than the control drink (P < 0.01). After consumption of the muffin, glucose responses were not significantly different; however, the insulin peak and incremental area under the curve (iAUC) tended to be lower for the L-arabinose muffin. Conclusion: L-arabinose and D-xylose are functional ingredients that can potentially lower the post-ingestive glycaemic and insulinaemic responses when added to realistic foods. However, the efficacy of applying L-arabinose appears to depend on the food matrix. Addition of these compounds needs further testing in other foods and in other populations, such as pre-diabetics.
Kristine E. Illøkken, Berit Johannessen, Mary E. Barker, Polly Hardy-Johnson, Nina Cecilie Øverby, Frøydis Nordgård Vik
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.7702

Abstract:
Background: There are no national arrangements for free school meals provision in Norway despite this being an important opportunity to improve children’s and adolescents’ nutritional status and ultimately their physical and cognitive development. During a one academic year (2014–2015), a group of Norwegian sixth graders were served a free healthy school meal in a project called ‘The School Meal Project’. Objective: To explore students’ and teachers’ experiences of receiving free school meals after the free school meal in 2015 and 5 years later. Design: In-depth, semi-structured interviews with separate groups in 2015 and in 2020 were conducted face to face or via telephone or digital platforms. The findings are based on 13 students (aged 12–16) and 5 teacher interviews. Findings: Thematic analysis identified four main themes that describe the perceived benefits of receiving free school meals: 1) the meal as a social event where students made new friends and learned new skills; 2) as an aid to forming healthy eating habits; and as an opportunity to 3) improve school functioning and 4) increase social equality among students. Discussion: Our analysis suggests that the free school meal may influence healthy behaviors not only at the individual level but also at the social-, physical-, and macro-levels. Methodological limitations, including self-selection bias, should be considered when interpreting our findings. Conclusion: This study provides unique insights into the social benefits for students of receiving free school meals. Our findings illustrate the potential of free school meals: eating healthy foods, sharing a meal together, and interaction between students and teachers at mealtime, to promote health, learning, and equality. In order to maximize these benefits through national implementation of free school meals, more understanding is needed of possible facilitators and barriers related to the provision and uptake of free school meals.
Xueliang Zhu, Zhichao Bi, Chen Yang, Yanhui Guo, Jieli Yuan, ,
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.6263

Abstract:
Background: Omega-3 polyunsaturated fatty acids (PUFAs) play beneficial roles in metabolism and health. Little is known about the effects of different doses of omega-3 PUFAs on gut microbiota. Objective: In this study, we focus on the effects of different doses of omega-3 PUFAs on gut microbiota and immunity. Design: BALB/c mice was first treated with ceftriaxone sodium for 7 days, and then they received saline or different doses of omega-3 PUFAs (30, 60 and 90 mg omega-3 PUFAs) via daily gavage for 21 days. Alterations of cecum microbiota; the tight junction proteins, zonula occludens 3 (ZO3) and occludin, in the ileal wall; serum lipopolysaccharide (LPS); Interleukin-10 (IL-10), interleukin-1β (IL-1β), and Tumour Necrosis Factor α (TNF-α) ; mucus SIgA levels were measured. Results: Compared with the ceftriaxone sodium administration group, significant increases in bacterial richness and diversity were observed in the 60- and 90-mg omega-3 PUFA groups, while only a slight increase was observed in the 30-mg omega-3 PUFA group. A higher percentage of several genera, including Lactobacillus, Helicobacter, and Ruminococcus, and a lower percentage of Bacteroides, Clostridium, and Prevotella were observed in the 60- and 90-mg omega-3 PUFA groups when compared with those in the 30-mg group. The expression of ZO3 and occludin proteins increased in 60- and 90-mg omega-3 PUFA groups compared with the natural recovery group. The mucus SIgA and serum IL-10 levels were increased, and serum levels of LPS, IL-1β, and TNF-α were decreased in the 60- and 90-mg omega-3 PUFA groups when compared with those in the ceftriaxone sodium-treated group. Conclusion: Different doses of omega-3 PUFAs have different therapeutic effects on the intestinal microbiota. The 60- and 90-mg omega-3 PUFA supplementation had better recovery effects on the gut microbiota and immunity than those of the 30 mg omega-3 PUFAs supplementation.
Yuan Cao, Guofeng Ren, Yahui Zhang, Hong Qin, Xin An, Yi Long, Jihua Chen, Lina Yang
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5689

Abstract:
Background: Insulin resistance, defined as a diminished ability to respond to the stimulation of insulin, is the main line for a variety of metabolic-related diseases. Punicalagin (PU), a hydrolyzable tannin of pomegranate juice, exhibits multiple biological properties, including anti-oxidant, anti-cancer and anti-inflammatory activities. Objective: This research study aimed at determining the protective effect of PU on insulin resistance and to uncover the underlying mechanism based on the gut microbiota, IKKβ/NF-κB pathway, and autophagy. Design: An insulin resistance animal model was established using C57BL/6 mice fed with a high-fat diet (HFD) for 8 weeks. The model included two groups continuing a HFD for 12 weeks with or without administering via gavage with PU 20 mg/kg/day. Changes in fasting plasma glucose levels, fasting serum insulin levels, glucose and insulin tolerance, glycolipid metabolism, gut microbiota composition (16S rRNA gene sequencing), inflammatory responses, and autophagy in the liver were evaluated. Body weight gain, glycolipid metabolic disorder, liver injury, as well as systemic and hepatic insulin sensitivity, were significantly attenuated after supplementing with PU. Results: This research study revealed that PU alleviated HFD-induced glucose and lipid disorders, liver injury and insulin resistance; decreased the Firmicutes/Bacteroides ratio, decreased the abundance of Coprococcus and Anaerotruncus, and increased Rikenellaceae; and decreased serum and liver tumor necrosis factor-alpha and interleukin-1β levels, inhibited liver IKKβ and NF-κB phosphorylation; and increased liver autophagy-related proteins LC3-II, P62, and Beclin1, and increased the number of liver autophagosomes. Conclusion: PU can improve HFD-induced insulin resistance, improved liver glucose and lipid metabolism disorder and liver injury, and the potential mechanism is that PU inhibited the IKKβ/NF-κB inflammatory pathway by regulating gut microbiota homeostasis and up-regulating liver autophagy
Tingting Miao, Yun Yu, Jin Sun, Aiguo Ma, Jinran Yu, Mengjun Cui, Liping Yang,
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5781

Abstract:
Background: Pre-eclampsia (PE) can result in severe damage to maternal and fetal health. It has been reported that gut microbiota (GM) had important roles in regulating the metabolic and inflammatory responses of the mother. However, investigations on GM in PE are rare. Objective: The objective of the present study was to investigate the changes of GM in PE and how to alter the GM composition in PE by dietary or dietary supplements. Design: We analyzed the composition changes in GM as well as the relationship between bacteria of different genera and clinical indices by amplifying the V4 region of the 16S ribosomal RNA gene in 12 PE patients and eight healthy pregnant women in East China. Results: In the PE group, the Observed Species Index was lower than that in the control group, indicating that the α-diversity of the microbiome in the PE group decreased. At phylum, family, and genus levels, the relative abundance of different bacteria in PE patients displayed substantial differences to those from healthy women. We noted a decreased abundance of bacteria of the phylum Actinobacteria (P = 0.042), decreased abundance of bacteria of the family Bifidobacteriaceae (P = 0.039), increased abundance of bacteria of the genus Blautia (P = 0.026) and Ruminococcus (P = 0.048), and decreased abundance of bacteria of the genus Bifidobacterium (P = 0.038). Among three enriched genera, bacteria of the genus Bifidobacterium showed a negative correlation with the systolic blood pressure (SBP), diastolic blood pressure (DBP), and dyslipidemia, which involved glucose metabolism, lipid metabolism, and the oxidative-phosphorylation pathway. The increased abundance of bacteria of the genera Blautia and Ruminococcus was positively correlated with obesity and dyslipidemia, which involved lipid metabolism, glycosyltransferases, biotin metabolism, and the oxidative-phosphorylation pathways. Moreover, women in the PE group ate more than women in the control group, so fetuses were more prone to overnutrition in the PE group. Conclusion: There is a potential for GM dysbiosis in PE patients, and they could be prone to suffer from metabolic syndrome. We speculate that alterations in the abundance of bacteria of certain genera (e.g. increased abundance of Blautia and Ruminococcus, and decreased abundance of Bifidobacterium) were associated with PE development to some degree. Our data could help to monitor the health of pregnant women and may be helpful for preventing and assisting treatment of PE by increasing dietary fiber or probiotics supplement.
Breanna Weigel, Natalie Eaton-Fitch, Rachel Passmore, Hélène Cabanas, Donald Staines, Sonya Marshall-Gradisnik
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5730

Abstract:
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem illness without a currently recognized pharmacological treatment. Dietary supplementation and modification have been posited as potential management strategies; however, their efficacy is controversial. Objective: This study aimed to assess the nutritional intake and supplement use of Australian ME/CFS patients and the perceived effect on health-related quality of life (HRQoL) for the first time in an Australian patient population. Design: Between February 2019 and January 2020, ME/CFS patients across Australia volunteered in this cross-sectional study in response to online advertisements. Eligible respondents were invited to complete three online self-administered questionnaires investigating their supplement use, nutritional intake, and HRQoL. The study participants’ supplement use and nutritional intake were summarized and compared with the population data returned from the Australian Health Survey (2011–2012). Multiple linear regression analysis was also performed to determine the effect of participants’ supplement use and nutrient intake on HRQoL. Results: Twenty-four eligible ME/CFS patients (54.2% meeting the International Consensus Criteria, 79.2% female, mean age = 43.4 ± 10.5 years) completed the online questionnaires. Supplement use was highly prevalent among the study sample (87.5%) and considerably more common when compared with population data (31.9%). Daily total fats and caffeine intakes were significantly higher among ME/CFS patients when compared with the Australian population (P = 0.009 and P = 0.033, respectively), whereas daily intakes of total carbohydrates and alcohol were significantly lower (both P < 0.001). No consistent trends between nutrition and supplement use with patients’ HRQoL could be identified. Conclusions: The daily diet and supplement use of ME/CFS patients appear to vary considerably from those of the general Australian population. Although the role of nutritional intake and supplement use on ME/CFS patients’ HRQoL remains unclear, dietary changes and the use of supplements appear to be of value to ME/CFS patients.
Valerie Tarasuk, Didier Brassard
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5256

Abstract:
Background: In Canada, regulatory changes have expanded marketing opportunities for voluntarily fortified products (VFPs), with micronutrient additions permitted at levels well in excess of human requirements. Objective: To examine how the consumption of VFPs relates to usual nutrient intakes in the Canadian population. Design: The 2015 Canadian Community Health Survey comprises single 24-h dietary intake recalls on a population-representative sample of 20,487 individuals aged 1 year and older, with second recalls on a subset of 7,608. The intake data included 15 food codes denoting VFP (e.g. energy drinks, fortified beverages, cereals, and bars). We assessed VFP consumption and estimated usual intake distributions for riboflavin, niacin, zinc, and vitamins A, B6, B12, and C for VFP consumers and non-consumers 14–50 years old (n = 8,442) using the National Cancer Institute method. We applied the ‘shrink and add’ method to estimate usual intakes among supplement users and assessed apparent benefits and risks by comparing usual intake distributions to EARs and ULs. Results: Only 2.4% of the population reported any consumption of VFP on the first 24-h recall. VFP consumers were overrepresented in the upper quartile of population intake distributions for niacin, riboflavin, vitamin B6, vitamin B12, and zinc. The median usual intakes of VFP consumers were 24–111% higher than the median usual intakes of non-consumers, and VFP consumers had significantly lower prevalence of inadequacy for riboflavin and vitamins A, B6, B12, and C. Irrespective of VFP consumption, usual intake distributions reached the ULs for vitamin A and zinc with the addition of supplement intakes. Discussion: Given the limited differentiation of VFP in this survey, we have likely underestimated nutrient exposure levels. Conclusions: VFP consumption was associated with elevated usual nutrient intakes, but we found limited evidence that it protected consumers from nutrient inadequacies or propelled intakes above tolerable upper levels.
, Noha M. Almoraie, Israa M. Shatwan
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5481

Abstract:
Background: Cardiovascular disease (CVD) is a main cause of mortality and disability worldwide. One of the key factors in the soaring prevalence of CVD globally has been nutrition transitions and changes in dietary patterns. Objective: This study investigated the association between two diet scores, namely, a high-fat dietary (HFD) pattern score and a Mediterranean diet (MedDiet) score, and CVD risk factors (obesity, hypertension, total cholesterol, and blood glucose) and serum 25 hydroxy vitamin D (25[OH]D) levels. Methods: Three hundred twenty-one participants were included in this study. Fasting blood tests were collected from all participants for biochemical measurements. Blood pressure and anthropometric measurements were also taken. A validated, semi-quantitative food frequency questionnaire was used to collect data on participants’ dietary intake. Dietary scores for the HFD pattern were calculated based on recommended food groups. MedDiet scores were calculated based on a previously validated method that contains 14 questions related to MedDiet. Both diet scores were classified into tertiles. Linear regression analyses were performed to assess the statistical significance of the tertile groups. Result: A significant association was found between HFD score and obesity when comparing the lowest tertile (27.3±4.6 kg/m2) of HFD scores with the medium tertile (29.2±5.7 kg/m2; P = 0.02). A higher HFD score was significantly associated with lower 25(OH)D levels (P = 0.02). In addition, a significant association was observed between MedDiet scores and 25(OH)D levels, with an increase in MedDiet score resulting in an increase in 25(OH)D levels (P = 0.01). Furthermore, a significant negative association between MedDiet scores and low-density lipoprotein levels was reported only in participants with CVD (P = 0.03). Conclusion: The results of this study revealed that HFD and MedDiet scores might have a role in the development of CVD and vitamin D deficiency among the Saudi Arabian population. Further studies are required using diet scores to assess the quality of dietary patterns and their association with an increased risk of diseases in Saudi Arabians.
, Wenche Barth Eide, Kristin R. Kardel, Per Ole Iversen, Ane C. Westerberg
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.7686

Abstract:
Background: The UN Sustainable Development Goal (SDG) 2 (‘Zero Hunger’) aims to end all forms of hunger and malnutrition by 2030. Thus, a range of different strategies are needed to facilitate the achievement of SDG 2 to overcome challenges and enable synergies between various SDG targets. Objective: The aim of this review is to highlight Africa’s progress toward SDG 2, including targets, strategies, synergies and challenges. Methods: We scrutinized published research articles in peer-reviewed journals, UN reports and in-country Africa reports (between 2015 and 2020) that were relevant to the current topic. Results: Several hunger indicators are showing slow progress or even deterioration in Africa. The prevalence of undernourishment in the general population was 19.1% in 2019 and is expected to increase to 25.7% by 2030. Improvements in child stunting in several regions in Africa are slow, especially in sub-Saharan Africa where about 34% of under-fives were stunted in 2012 and 31% in 2019. In Eastern Africa, stunting prevalence decreased from 38% in 2012 to 34% in 2019. Major drivers of hunger are poor governance and state fragility, war and conflicts, increasing inequality, weak economic development, climate change, biodegradation – and now lately the Covid 19 pandemic – factors that all increase food insecurity. Conclusion: Africa is off track to reach SDG – ‘Zero Hunger’ – by 2030. Current efforts and progress are insufficient. Africa must champion the SDG agenda on a national, regional and global level to facilitate synergies to unlock the potential for reaching ‘Zero Hunger’ throughout the continent.
Sasikala M. Chinnappan, Annie George, Pragya Pandey, Govinda Narke, Yogendra Kumar Choudhary
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5647

Abstract:
Background: Low testosterone levels cause physiological changes that compromise the quality of life in ageing men. A standardised water extract from the root of Eurycoma longifolia (EL), known as Physta®, is known to increase testosterone levels. Objective: To evaluate the safety and efficacy of Physta® in improving the testosterone levels and quality of life in ageing male subjects. Design: This randomised, double-blind, placebo-controlled study enrolled 105 male subjects aged 50–70 years with a testosterone level <300 ng/dL, BMI ≥ 18 and ≤30.0 kg/m2. The subjects were given either Physta® 100 mg, 200 mg or placebo daily for 12 weeks. The primary endpoints were changes in serum total and free testosterone levels. The secondary endpoints included changes in the level of sex hormone-binding globulin (SHBG), dihydroepiandrosterone (DHEA), glycated haemoglobin (HbA1c), insulin-like growth factor-1 (IGF-1), thyroid function tests (T3, T4, TSH and Free T3) and cortisol. Changes in Ageing Male Symptoms (AMS) score, Fatigue Severity Scale (FSS) score and muscle strength are other secondary endpoints. The safety of the intervention products was measured by complete blood count, lipid profile, liver and renal function tests. Results: There was a significant increase in the total testosterone levels at week 12 (P < 0.05) in the Physta® 100 mg group and at weeks 4 (P < 0.05), 8 (P < 0.01) and 12 (P < 0.001) in the Physta® 200 mg group compared to placebo. No significant between-group differences in free testosterone levels were observed but a significant within-group increase occurred at weeks 4 (P < 0.01), 8 (P < 0.001) and 12 (P < 0.001) in the Physta®100 mg group and at weeks 2 (P < 0.01), 4 (P < 0.01), 8 (P < 0.001) and 12 (P < 0.001) in the Physta® 200 mg group. The AMS and FSS showed significant reduction (P < 0.001) in total scores at all time-points within- and between-group in both Physta® groups. DHEA levels significantly increased (P < 0.05) within-group in both Physta® groups from week 2 onwards. Cortisol levels significantly (P < 0.01) decreased in the Physta® 200 mg group, while muscle strength significantly (P < 0.001) increased in both Physta® groups at week 12 in the within-group comparison. There were no significant changes in SHBG. No safety related clinically relevant changes were observed. Conclusion: Supplementation of Physta® at 200 mg was able to increase the serum total testosterone, reduce fatigue and improve the quality of life in ageing men within 2 weeks’ time. Trial registration: This clinical study has been registered in ctri.nic.in (CTRI/2019/03/017959).
Ge Song, Wentao Qi, Yong Wang, Shaojie Pang, Yong Li
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5589

Abstract:
Aims: To study the metabolic effects of fructose, glucose and saccharose in a moderate dose by analyzing changes of blood indicators, pancreas inflammation, liver fat accumulation and intestinal microbiota in normal Sprague-Dawley (SD) rats. Subjects and methods: Six-week-old rats were assigned to four groups (n = 10), which were gavaged with normalsaline (Con), glucose dissolved in normal saline (Glu), saccharose-glucose dissolved in normal saline (Sac), and fructose dissolved in normal saline (Fru) for 20 weeks. Results: No significant differences in body weight and blood parameters including total cholesterol (TC), total triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), lipase (LPS) and free fatty acid (FFA) among the Con, Glu, Sac and the Fru group. The fructose can significantly (P < 0.05) decrease fasting and postprandial blood glucose increase compared to glucose, and the risk of pancreas inflammation and liver fat accumulation induced by fructose is lower than glucose in rats. We found there were no significant differences in intestinal microbial diversity. At the family level, rats in the Glu group had a relatively higher abundance of Peptostreptococcaceae and rats in the Fru group had a relatively higher abundance of Bacteroidaceae. Moreover, the proportions of Peptostreptococcaceae romboutsia and Staphylococcus lentus in the Glu group were significantly higher than in the Fru group, while the proportions of Lachnospira; Lachnospiraceae blautia, Bacteroides and Cellulosilyticus in the Fru group were significantly higher than in the Glu group. The concentration of isobutyric acid was relatively lower in all the sugar treated groups than in the Con. A significant decrease in isobutyric acid was found on comparing the Fru group to the Con group (P < 0.05). Conclusion: Fructose, glucose and sucrose made no significant changes on rats in body weight, blood indicators, organ index and bacterial diversity. Moreover, fructose can potentially attenuate fasting and postprandial blood-glucose increase, pancreas inflammation and liver-fat accumulation when compared to glucose in mild doses. The relative abundance of six kinds of bacterial genera was found significantly different between rats fed on fructose and glucose.
Lin Zhou, Wenwen Gu, Fuguang Kui, Fan Gao, Yuji Niu, Wenwen Li, Yaru Zhang, Lijuan Guo, Junru Wang, , et al.
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.7526

Abstract:
Background: Chronic obstructive pulmonary disease (COPD) is an important risk factor for developing lung cancer. Aged citrus peel (chenpi) has been used as a dietary supplement for respiratory diseases in China. Objective: To explore the mechanism and candidate compounds of chenpi preventing COPD and its progression to lung cancer. Methods: The active components and potential targets of chenpi were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease-associated targets of COPD and lung cancer were collected in the Gene Cards and TTD database. The component-target network and PPI network were constructed using the Cytoscape 3.8.0 software. David database was used for GO and KEGG enrichment analysis. The main active components were verified by using the autodock Vina 1.1.2 software. Mouse lung cancer with COPD was induced by cigarette smoking (CS) combined with urethane injection to confirm preventing the effect of hesperetin (the candidate compound of chenpi) on COPD progression to lung cancer and its underlying mechanisms. Results: The network analysis revealed that the key active components of chenpi (nobiletin, naringenin, hesperetin) regulate five core targets (AKT1, TP53, IL6, VEGFA, MMP9). In addition, 103 potential pathways of chenpi were identified. Chenpi can prevent COPD and its progression to lung cancer by getting involved in the PI3K-Akt signaling pathway and MAPK signaling pathway. Molecular docking indicated that hesperetin had better binding activity for core targets. In mouse lung cancer with COPD, treatment with hesperetin dose-dependently improved not only lung tissue injury in COPD but also carcinoma lesions in lung cancer. Meanwhile, hesperetin could suppress the protein expression of AKT1, IL6, VEGFA, MMP9 and up-regulate the protein expression of TP53, and thus reduced the risk of COPD progression to lung cancer. Conclusion: Hesperetin is a candidate compound of chenpi that helps in preventing COPD and its progression to lung cancer by regulating AKT1, IL6, VEGFA, MMP9 and TP53.
Licong Zhang, Tao Guo, Na Zhan, Taotao Sun, Anshan Shan
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.3448

Abstract:
Background: Antibiotics are very effective for treating diarrhea in weaned pigs, but the global prohibition of antibiotics makes it urgent to find an alternative to antibiotics. Objective: An experiment was conducted to determine the antimicrobial activity of a linear trpzip-like β-hairpin antimicrobial peptide WK3 in vivo and to assess its effects on growth performance and intestinal health. Design: Thirty-two piglets were weaned at 21 days and housed in individual metabolic cages, which were randomly divided into four groups and were maintained on a corn-soybean meal-based basal diet. Group 1 included a blank group. Groups 2, 3, and 4 were orally infected by feeding with Enterotoxigenic Escherichia coli (ETEC) K88, which was followed by saline treatment (group 2), enrofloxacin injection at a dose of 2.5 mg/ kg (group 3), and WK3 injection at a dose of 2 mg/kg (group 4). The experiment lasted for 6 days, and feed and water were provided ad libitum. Results: Both WK3 and enrofloxacin effectively attenuated diarrhea and improved growth performance of piglets. Compared with the control group, WK3 significantly improved the villus height in the ileum (P < 0.05) but did not affect the villus height in the duodenum or jejunum. Additionally, we did not observe any obvious difference in crypt depth or villus height/crypt depth among the duodenum, jejunum and ileum (P > 0.05). WK3 also reduced the numbers of Enterococcus spp (P < 0.01) in the cecal contents, and the number of Enterobacterium spp tended to decrease (0.05 < P < 0.1). Moreover, the jejunal mucosa of the WK3 group exhibited lower interleukin-1α (IL-1a; P < 0.01), toll-like receptors-4 (TLR-4; P < 0.05), and myeloid differentiation primary response 88 (MyD88; P < 0.01) messenger ribonucleic acid (mRNA) expression levels. The jejunum of the WK3 group also exhibited an increased antioxidant capacity, reduced concentration of malondialdehyde (MDA; P < 0.05), and enhanced superoxide dismutase (SOD) activity (P < 0.05). Conclusions: WK3 has the potential to replace antibiotics as a new generation feed additive.
Cui Lin, Jihua Chen, Minmin Hu, Wenya Zheng, Ziyu Song,
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.7577

Abstract:
Background: Obesity is defined as an imbalance between energy intake and expenditure, and it is a serious risk factor of non-communicable diseases. Recently many studies have shown that promoting browning of white adipose tissue (WAT) to increase energy consumption has a great therapeutic potential for obesity. Sesamol, a lignan from sesame oil, had shown potential beneficial functions on obesity treatment. Objective: In this study, we used C57BL/6J mice and 3T3-L1 adipocytes to investigate the effects and the fundamental mechanisms of sesamol in enhancing the browning of white adipocytes to ameliorate obesity. Methods: Sixteen-week-old C57BL/6J male mice were fed high-fat diet (HFD) for 8 weeks to establish the obesity models. Half of the obese mice were administered with sesamol (100 mg/kg body weight [b.w.]/day [d] by gavage for another 8 weeks. Triacylglycerol (TG) and total cholesterol assay kits were used to quantify serum TG and total cholesterol (TC). Oil red O staining was used to detect lipid droplet in vitro. Mito-Tracker Green was used to detect the mitochondrial content. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the levels of beige-specific genes. Immunoblotting was used to detect the proteins involved in beige adipocytes formation. Results: Sesamol decreased the content of body fat and suppressed lipid accumulation in HFD-induced obese mice. In addition, sesamol significantly upregulated uncoupling protein-1 (UCP1) protein in adipose tissue. Further research found that sesamol also significantly activated the browning program in mature 3T3-L1 adipocytes, manifested by the increase in beige-specific genes and proteins. Moreover, sesamol greatly increased mitochondrial biogenesis, as proved by the upregulated protein levels of mitochondrial biogenesis, and the inhibition of the proteins associated with mitophagy. Furthermore, β3-adrenergic receptor (β3-AR), protein kinase A-C (PKA-C) and Phospho-protein kinase A (p-PKA) substrate were elevated by sesamol, and these effects were abolished by the pretreatment of antagonists β3-AR. Conclusion: Sesamol promoted browning of white adipocytes by inducing mitochondrial biogenesis and inhibiting mitophagy through the β3-AR/PKA pathway. This preclinical data promised the potential to consider sesamol as a metabolic modulator of HFD-induced obesity.
Frauke Assmus, Cecilia Galbete, Sven Knueppel, Matthias B. Schulze, Erik Beune, Karlijn Meeks, Mary Nicolaou, Stephen Amoah, Charles Agyemang, Kerstin Klipstein-Grobusch, et al.
Food & Nutrition Research; https://doi.org/10.29219/fnr.v65.5435

Abstract:
Background: African populations in sub-Saharan Africa and African migrants in Europe are facing a rapid upsurge in obesity. This trend has been related to urbanization, migration and associated shifts in lifestyle, including dietary habits. Whether changes in eating patterns contribute to the rising burden of obesity among African populations is currently unknown. Objective: Our aims in conducting this study were to characterize eating patterns among Ghanaian adults living in their country of origin and in Europe and to explore associations of meal patterns with body mass index (BMI). Design: Within the cross-sectional RODAM (Research on Obesity and Diabetes among African Migrants) study, data of single 24-h dietary recalls from Ghanaian adults in rural Ghana (n = 20), urban Ghana (n = 42), and Europe (n = 172) were recorded. Eating frequencies, energy intake, and macronutrient composition of eating occasions (EOs, i.e. meals or snacks) were compared between study sites based on descriptive statistics and χ2-/Kruskal–Wallis tests. Results: A rising gradient of EO frequencies from rural Ghana through urban Ghana to Europe was observed, mainly reflecting the differences in snacking frequencies (≥1 snack per day: 20 vs. 48 vs. 52%, P = 0.008). Meal frequencies were similar across study sites (≥3 meals per day: 30 vs. 33 vs. 38%, P = 0.80). Meals were rich in carbohydrates (median 54.5, interquartile range (IQR): 43.2–64.0 energy%) and total fats (median: 27.0, IQR: 19.9–34.4 energy %); their protein content was lowest in rural Ghana, followed by urban Ghana and Europe (P = 0.0005). Snacks mainly contained carbohydrates (median: 75.7, IQR: 61.0–89.2 energy%). In linear regression analyses, there was a non-significant trend for an inverse association between snacking frequencies and BMI. Discussion and conclusions: The observed integration of carbohydrate-dense snacks into the diet supports the growing evidence for a nutrition transition among African populations undergoing socioeconomic development. This analysis constitutes a starting point to further investigate the nutritional implications of increased snacking frequencies on obesity and metabolic health in these African populations.
, María Dolores Pérez-Carrión, Lucía Casariego Olavarría, Luis F. Alguacil, María José Polanco Mora, Carmen González-Martín
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5709

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Food-related disorders are increasingly common in developed societies, and the psychological component of these disorders has been gaining increasing attention. Both overnourishment with high-fat diets and perinatal undernourishment in mice have been linked to a higher motivation toward food, resulting in an alteration in food intake. Clusterin (CLU), a multifaced protein, is overexpressed in the nucleus accumbens (NAc) of overfed rats, as well as in those that suffered chronic undernutrition. Moreover, an increase of this protein was observed in the plasma of obese patients with food addiction, suggesting the implication of CLU in this eating disorder. To characterize CLU’s cellular mechanisms, in vitro experiments of undernutrition were performed using dopaminergic SH-SY5Y cells. To mimic in vivo dietary conditions, cells were treated with different fetal bovine serum (FBS) concentrations, resulting in control (C group) diet (10% FBS), undernourishment (U group) diet (0.5% FBS), and undernourishment diet followed by restoration of control diet (UC group) (0.5 + 10% FBS). Undernourishment compromised cell viability and proliferation, and concomitantly increased CLU secretion as well as the cytosolic pool of the protein, while decreasing the mitochondrial level. The restoration of normal conditions tended to recover cell physiology, and the normal levels and distribution of CLU. This research study is a step forward toward the characterization of clusterin as a potential marker for food addiction and nutritional status.
Eunyoung Lee, Mak-Soon Lee, Eugene Chang, Chong-Tai Kim, Ae-Jin Choi, In-Hwan Kim, Yangha Kim
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.7587

Abstract:
Background: Mulberry leaf (Morus alba L.) contains multiple bioactive ingredients and has been used in the treatment of obesity, diabetes, inflammation, and atherosclerosis. High hydrostatic pressure (HHP) processing has been developed for the extraction of bioactive compounds from plants. However, the hypocholesterolemic effect of the HHP extract from mulberry leaves and its underlying mechanism have never been investigated. Objective: The specific aim of the present study was to investigate the hypocholesterolemic property of a novel extract obtained from mulberry leaves under HHP in rats. Design: Sprague–Dawley rats were divided into four groups and fed either a normal diet (NOR), a high cholesterol diet containing 1% cholesterol and 0.5% cholic acid (HC), an HC diet containing 0.5% mulberry leaf extract (ML), or a 1% mulberry leaf extract (MH) for 4 weeks. Results: High hydrostatic pressure extract of mulberry leaves significantly reduced the HC-increased serum levels of triglyceride (TG), cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), and hepatic contents of TG and TC. The HHP extraction from mulberry leaves also increased the HC-decreased fecal TC and bile acid levels without changing body weight, food intake, liver weight, and serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) (P < 0.05). The mulberry leaf extract significantly enhanced the expression of hepatic genes such as cholesterol 7 alpha-hydroxylase (CYP7A1), liver X receptor alpha (LXRα), and ATP-binding cassette transporters, ABCG5/ABCG8, involved in hepatic bile acid synthesis and cholesterol efflux (P < 0.05). In addition, the HHP extraction of mulberry leaves significantly suppressed hepatic microRNA(miR)-33 expression and increased adenosine monophosphate-activated protein kinase (AMPK) activity. Conclusion: These results suggest that the HHP extract of mulberry leaves lowers serum cholesterol levels by partially increasing hepatic bile acid synthesis and fecal cholesterol excretion through the modulation of miR- 33 expression and AMPK activation in the liver.
Meilan Xue, Hui Liang, Zhitong Zhou, Ying Liu, Xinjia He, Zheng Zhang, Ting Sun, Jia Yang, Yimin Qin, Kunpeng Qin
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5384

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Background: Alcoholic liver disease is caused as a result of chronic alcohol consumption. In this study, we used an alcoholic liver injury mouse model to investigate the effect of fucoidan on ethanol-induced liver injury and steatosis and the underlying mechanisms. Methods: All mice were randomly divided into four groups: 1) control group, 2) model group, 3) diammonium glycyrrhizinate treatment group (200 mg/kg body weight), and 4) fucoidan treatment group (300 mg/kg body weight). Administration of ethanol for 8 weeks induced liver injury and steatosis in mice. Results: Fucoidan treatment decreased serum alanine aminotransferase activity, serum total cholesterol levels, and hepatic triglyceride levels, and improved the morphology of hepatic cells. Fucoidan treatment upregulated the expression of AMPKα1, SIRT1, and PGC-1α and inhibited the expression of ChREBP and HNF-1α. The levels of hepatic IL-6 and IL-18 were significantly decreased in the fucoidan group. Further, the levels of cytochrome P450-2E1 (CYP2E1), glucose-regulated protein (GRP) 78, and 3-nitrotyrosine (3-NT) in hepatic tissues were reduced in the fucoidan group as compared to the model group. Fucoidan significantly reversed the reduction of ileac Farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) levels induced by alcohol- feeding and reduced CYP7A1 (cholesterol 7α-hydroxylase) expression and total bile acid levels in the liver tissue. In addition, fucoidan regulated the structure of gut flora, with increased abundance of Prevotella and decreased abundance of Paraprevotella and Romboutsia as detected by 16S rDNA high-throughput sequencing. Conclusion: Fucoidan inhibited alcohol-induced steatosis and disorders of bile acid metabolism in mice through the AMPKα1/SIRT1 pathway and the gut microbiota–bile acid–liver axis and protected against alcohol- induced liver injury in vivo.
, Dina Doblaug Solli, Maria Wik Markhus, Hanne K. Mæhre, Lisbeth Dahl, Sigrun Henjum, Jan Alexander, Patrick-Andre Korneliussen, Lise Madsen, Marian Kjellevold
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.7584

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Background: Seaweeds and kelps, also known as macroalgae, have long been common in the East-Asian diet. During recent years, macroalgae have entered the global food market, and a variety of macroalgae products are now available for consumers. Some macroalgae species are known to be particularly rich in iodine, but little data regarding the iodine content of macroalgae-containing foods exists. Objective: The aim of this research study was to analyse the iodine content in a large variety of commercially available macroalgae-containing foods and supplements and to evaluate whether such products are sources of adequate dietary iodine. Design: Ninety-six different products were collected after surveying the Norwegian market for commercially available macroalgae products, collected from three categories: 1) wholefood macroalgae products (n = 43), 2) macroalgae-containing foods (n = 39), and 3) dietary supplements containing macroalgae (n = 14). All products were analysed for iodine content by inductively coupled plasma-mass spectrometry (ICP-MS). Results: The iodine content in one portion of wholefood macroalgae products ranged from 128 to 62,400 μg. In macroalgae-containing foods, the iodine content ranged from 30 to 25,300 μg per portion, and in supplements it ranged from 5 to 5,600 μg per daily dose. The species with the highest analysed iodine content were oarweed, sugarkelp and kombu, with mean iodine levels of 7,800, 4,469 and 2,276 μg/g, respectively. For 54 products, the intake of one portion or dose would exceed the tolerable upper intake level (UL) for iodine. Discussion and conclusion: The iodine content in the included products was variable and for most products high, exceeding the tolerable upper intake level (UL) if consumed as a serving or portion size. The labelling of macroalgae species included, and declaration of iodine content, were inadequate or inaccurate for several products. As macroalgae-containing products are unreliable iodine sources, inclusion of such products in the diet may pose a risk of consuming excessive amounts of iodine.
Vincenzo Nobile, Irene Schiano, Ana Peral, Silvana Giardina, Eleonora Spartà,
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5619

Abstract:
Background: Air pollution exposure is one of the major threats to skin health and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure to air pollutants, especially in urban areas, strategies to protect the skin are needed. Plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants and a dietary approach based on these compounds could provide an efficient protection measure. Objective: Here we investigated the efficacy of a commercially available polyphenol-enriched dietary supplement (Zeropollution®) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian subjects exposed to air pollution. Zeropollution is composed of four standardized herbal extracts: Olea europaea leaf, Lippia citriodora, Rosmarinus officinalis, and Sophora japonica. Design: A double-blind randomized, parallel group study was carried out on 100 outdoor workers living in a polluted urban European area (Milan) to assess the efficacy of the dietary supplement. The total antioxidant capacity on saliva (FRAP), the oxidative damage on skin (lipoperoxides content), skin moisturization (corneometer), transepidermal water loss (tewameter), skin radiance and colour (spectrophotometer), skin elasticity (cutometer), skin sebum content (sebumeter), and the skin roughness (image analysis) were measured. Results: Both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical-monitored parameters, in both Caucasian and Asian individuals. Some of the positive effects such as decreased wrinkle depth, increased elasticity and firmness, improved skin moisturization and transepidermal water loss, and reduced dark spots pigmentation were statistically significant as early as 2 weeks of product consumption. Conclusions: The results of the study indicate reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area. Therefore, the oral intake of this four-plant based supplement could be considered a complementary nutrition strategy to avoid the negative effects of environmental pollution exposure.
, Marlene Slydahl, Monica Hellmann, Lisa Garnweidner-Holme, Knut E. A. Lundin, Christine Henriksen, Vibeke H. Telle-Hansen
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.6121

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Background: Celiac disease is a chronic autoimmune disease triggered by gluten exposure in genetically predisposed individuals. A life-long intake of a gluten-free (GF) diet is required for its management. Wheat, rye and barley are eliminated in a GF diet and the nutritional adequacy of the diet has been questioned. In Norway, cereals and bread constitute a key role of the diet and are the main source of fiber intake. Gluten restrictions may therefore offer important implications for nutrient adequacy especially linked to fiber intake in people with celiac disease. Objective: The aim of the study was to investigate the nutritional quality and price of GF products and compare with gluten-containing counterparts available at instead of in the Norwegian market. Design: The macronutrient content of 423 unique GF products were compared with 337 equivalents with gluten. All products were selected from grocery stores and web-based shops, with the aim of including as many GF products as possible. Listed macronutrients content and price in 11 different food categories were compared to gluten-containing counterparts with Wilcoxon signed rank test. Results: The GF products contained less protein and fiber, and higher content of saturated fat, carbohydrate and salt compared to the gluten-containing products. The total amount of fat was not different between the groups. A similar pattern was found within several of the food categories. More gluten-containing products met the nutrition claim “high in fiber” (fiber > 6 g/100 g) compared to the GF products. The price of the GF products was higher; ranging from 46%–443% more expensive than the gluten-containing products. Conclusion: GF products are less nutritious and have a higher price compared to equivalent gluten-containing products. Knowing that an unhealthy diet is the most important risk factor for developing non-communicable diseases, the nutritional quality of a GF diet needs to be addressed and should be improved.
Yue Sun, Hong Qin, Huihui Zhang, Xiangling Feng, Lina Yang, De-Xing Hou, Jihua Chen
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.6355

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Background: Fisetin, a natural potent flavonoid, has various beneficial, pharmacological activities. In this study, we investigated expression changes of the fisetin regulating genes in lipopolysaccharide (LPS)-treated RAW264.7 cells and explored the role of fisetin in inflammation and autophagy. Methods and results: Microarray analysis identified 1,071 genes that were regulated by fisetin in LPS-treated RAW264.7 cells, and these genes were mainly related to the process of immune system response. Quantitative real-time polymerase chain reaction and Bio-Plex analysis indicated that fisetin decreased the expression and secretion of several inflammatory cytokines in cells administered with LPS. Western blot analysis and immunofluorescence assay showed that fisetin decreased microtubule-associated protein 1 light-chain 3B (LC3B) and lysosome-associated membrane protein 1 (LAMP1) expression in LPS-treated cells, while the autophagy inhibitor chloroquine (CQ) could partially reverse this effect. In addition, fisetin reduced the elevated expression of p-PI3K, p-AKT and p-mTOR induced by LPS in a concentration-dependent manner. Conclusions: Fisetin diminished the expression and secretion of inflammatory cytokines and facilitated autophagosome- lysosome fusion and degradation in LPS-treated RAW264.7 cells via inhibition of the PI3K/ AKT/mTOR signaling pathway. Overall, the results of this study provide new clues for the anti-inflammatory mechanism of fisetin and explain the crosstalk between autophagy and inflammation to some extent.
Kristin S. Magnusdottir, Ellen A. Tryggvadottir, Ola K. Magnusdottir, Laufey Hrolfsdottir, Thorhallur I. Halldorsson, Bryndis E. Birgisdottir, Ingibjorg T. Hreidarsdottir, Hildur Hardardottir, Ingibjorg Gunnarsdottir
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5574

Abstract:
Background: Vitamin D deficiency has been associated with an increased risk of gestational diabetes mellitus (GDM), one of the most common pregnancy complications. The vitamin D status has never previously been studied in pregnant women in Iceland. Objective: The aim of this research study was to evaluate the vitamin D status of an Icelandic cohort of pregnant women and the association between the vitamin D status and the GDM incidence. Design: Subjects included pregnant women (n = 938) who attended their first ultrasound appointment, during gestational weeks 11–14, between October 2017 and March 2018. The use of supplements containing vitamin D over the previous 3 months, height, pre-pregnancy weight, and social status were assessed using a questionnaire, and blood samples were drawn for analyzing the serum 25‑hydroxyvitamin D (25OHD) concentration. Information regarding the incidence of GDM later in pregnancy was collected from medical records. Results: The mean ± standard deviation of the serum 25OHD (S-25OHD) concentration in this cohort was 63±24 nmol/L. The proportion of women with an S-25OHD concentration of ≥ 50 nmol/L (which is considered adequate) was 70%, whereas 25% had concentrations between 30 and 49.9 nmol/L (insufficient) and 5% had concentrations < 30 nmol/L (deficient). The majority of women (n = 766, 82%) used supplements containing vitamin D on a daily basis. A gradual decrease in the proportion of women diagnosed with GDM was reported with increasing S-25OHD concentrations, going from 17.8% in the group with S-25OHD concentrations < 30 nmol/L to 12.8% in the group with S-25OHD concentrations ≥75 nmol/L; however, the association was not significant (P for trend = 0.11). Conclusion: Approximately one-third of this cohort had S-25OHD concentrations below adequate levels (< 50 nmol/L) during the first trimester of pregnancy, which may suggest that necessary action must be taken to increase their vitamin D levels. No clear association was observed between the vitamin D status and GDM in this study.
Dan Hao, Xiao Wang, Xiaogang Wang, Bo Thomsen, Kaixing Qu, Xianyong Lan, Yongzhen Huang, Chuzhao Lei, Bizhi Huang, Hong Chen
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5453

Abstract:
Background: Resveratrol (RSV), a phenolic compound, is present in many human dietary sources, such as peanuts, peanut butter, grapes skin, and grape wine. RSV has been widely known for its benefits on human health. Beef from cattle skeletal muscle is one of the main sources of protein for human consumption. Previous studies have also found that pork and chicken qualities are influenced by the feed supplementation with RSV. In addition, our previous study demonstrated the RSV effects on bovine myoblast differentiation using messenger RNA (mRNA) data. In this study, we mainly focused on the influences of RSV on microRNA (miRNA) expression. Method: We used 20 μM RSV to treat primary bovine myoblasts and extracted RNA for miRNA sequencing. After quality control and alignment for clean reads, we conducted quantification and analysis of differentially expressed (DE) miRNAs in the case (RSV-treated) group versus control (non-RSV treated) group. Next, we predicted the target genes for the DE miRNAs and analyzed them for the enrichments of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results: Finally, we identified 93 DE miRNAs (adjusted P-value < 0.05), of them 44 were upregulated and 49 were downregulated. Bta-miR-34c was the most significantly upregulated miRNA. In silico, prediction results indicated 1,869 target genes for the 93 DE miRNAs. GO enrichment analysis for the genes targeted by DE miRNAs revealed two significant GO terms (adjusted P-value < 0.05), in which the most significant one was stereocilium (GO:0032420). KEGG enrichment analysis showed five significant pathways, and the top significant KEGG pathway was the insulin signaling pathway (bta04910) (adjusted P-value < 0.05). Conclusions: This study provided an improved understanding of effects of RSV on primary bovine myoblast differentiation through the miRNA modulations. The results suggested that RSV could promote differentiation of primary bovine myoblast by stimulating the miRNA expressions. The target genes of DE miRNAs were significantly enriched in the insulin signaling pathway, thus potentially contributing to improving muscle leanness by increasing the energy metabolism.
Yu Zhang, Kui Yang, Song Hou, , Jonathan Crush
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5501

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Background: In coping with the coronavirus disease 2019 (COVID-19) epidemic, cities adopted social isolation and lockdown measures; however, little is known about the impacts of these restrictions on household food security. Objective: This study provides a timely assessment of household food insecurity (HFI) in the Chinese city of Wuhan during the COVID-19 epidemic period and also investigates its determinant factors. Design: We collected valid data on food insecurity from 653 households in Wuhan via an online questionnaire in March 2020. The Household Food Insecurity Access Scale Score (HFIASS) was used to measure HFI, and a multiple linear regression model was used to determine the HFIASS. Results: The mean HFIASS in Wuhan was 9.42 (standard deviation: 5.82), with more than 50% of the households had an HFIASS < 9. Compared with normal conditions, lockdown measures had a huge negative impact on household food security. The results revealed that socio-demographic characteristics remained the underlying determinants of HFIASS during the epidemic. Households in Wuhan with local Hukou (city household registration) and self-owned property had a lower risk of food insecurity. Discussion and conclusion: After the restriction of conventional food access channels, intermediary food purchase methods such as group purchasing, shopping with the help of neighborhood committees, property management agents, and volunteers became the most important or the only channel for residents to access food. There were similarities in the use of these intermediary channels. Based on the probability that the epidemic will continue and the probability of similar public health-related outbreaks in the future, the study calls for a more resilient and responsive sustainable food supply system by harnessing the capacity of communities, e-commerce and rapid logistics.
Lang You, Fengxia Li, Yan Sun, Liang Luo, Jian Qin, Tao Wang, Yuchen Liu, Ruogu Lai, Ruohan Li, Xiaoran Guo, et al.
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.4246

Abstract:
Background: Obesity is a principal risk factor for the development of type 2 diabetes and cardiovascular diseases. Natural plants and/or foods play an important role in the management of obesity. Acalypha australis L. (AAL) is a kind of potherb popular among Asian populations, and it is also consumed as a food ingredient and traditional herbal medicine. Objective: We investigated the effects of water extract from AAL on high-fat-diet (HFD)-induced obese mice and 3T3-L1 adipocytes to develop a new functional food material. Design: Nine-week-old male mice were randomly divided into control (chow diet, n = 6) and HFD (n = 30) group. From 12-weeks onward, mice in the HFD group were further separated into model (saline, 6 mL/ kg), simvastatin (0.11 mg/mL, 6 mL/kg), and AAL treatment (low, middle, and high dosage: 300, 600, and 900 mg/kg) group, with 6 animals per group, while mice in the control group were treated with saline (6 mL/ kg). Food intake, body/fat weight, liver/kidney indexes, and lipid profiles were determined. Tissues were fixed with formalin for pathological examination. Western blotting and PCR were performed to evaluate the protein and mRNA expression in 3T3-L1 adipocytes. Oil Red O staining was used to determine lipid accumulation. Results: AAL administration significantly suppressed body weight gain, and reduced fat pad weight and Lee’s index in obese mice, but had no effect on liver/kidney index. AAL also reduced serum cholesterol, triglyceride, and LDL-C and increased HDL-C levels. Histological analysis revealed that AAL significantly ameliorated lipid accumulation in the liver and subcutaneous adipose tissue. In vitro, Oil Red O staining showed that AAL inhibited adipose differentiation by down-regulating the gene and protein expression of PPARγ and C/EBPα. AAL also reversed HFD-induced intestinal dysbacteriosis. Conclusion: AAL water-soluble extract has a significant anti-adipogenic effect in the HFD-induced obese mice model.
Mai Hijikata, , Takamasa Ichijo, Takahisa Hirose
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5490

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Aims: To identify factors predicting a need for insulin therapy in gestational diabetes mellitus (GDM) by comparing plasma glucose (PG) levels in a 75-g oral glucose tolerance test (75-g OGTT) with those in a 500-kcal meal tolerance test (MTT) containing 75 g of carbohydrate. Subjects and methods: The MTT was performed in 61 patients who diagnosed with GDM by a 75-g OGTT (age, 33.2 ± 4.5 years; prepregnancy body mass index, 22.6 ± 4.7 kg/m2; number of gestational weeks, 25.1 ± 6.4 weeks). PG and serum insulin levels were measured before the meal and up to 180 min after the meal. The insulin secretion capacity and resistance index were calculated. Results: PG levels increased from 86.8 ± 8.8 mg/dL at fasting to 132.7 ± 20.1 mg/dL at 30 min, and 137.8 ± 27.7 mg/dL at 60 min after MTT in the 35 patients with needed insulin therapy; these levels were significantly higher than those in the 26 patients, who only needed diet therapy. The patients with needed insulin therapy had significantly higher fasting PG levels in the 75-g OGTT, PG levels at fasting and 30 min after the MTT, and homeostasis model assessment of insulin resistance (HOMA-IR), and a significantly lower disposition index (DI) and insulin index than patients treated by diet alone. Receiver operating characteristic curve analysis was performed for factors involved in insulin therapy, with the following cutoff values: fasting PG in the 75-g OGTT, 92 mg/dL; PG 30 min after MTT, 129 mg/dL; HOMA-IR, 1.51; DI, 3.9; HbA1c, 5.4%. Multivariate analysis revealed that the 30-min PG level after MTT and HOMA-IR predicted insulin therapy. Conclusion: PG levels at 30 min after MTT may be useful for identifying patients with GDM, who need insulin therapy.
Amandine Duclau, Fanny Abad, Antoine Adenis, Nadia Sabbah, Malika Leneuve,
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5268

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Background: Involved in physical and brain development, immunity and metabolism, micronutrients have profound health effects. The nutritional status of pregnant women is a major determinant of foetal health. French Guiana has a rapid population growth. Social inequalities, cultural practices and gastrointestinal nematode infections in French Guiana could affect the prevalence of these deficiencies. The main objective of the present study was to estimate the prevalence of micronutrient deficiency among pregnant women in French Guiana. The secondary objective was to identify socio-demographic, dietary, obstetrical and neonatal risk factors associated with deficiencies. Methods: Pregnant women over 22 weeks of pregnancy hospitalized for delivery at the Obstetrical Emergency Department of the Hospital Center in Cayenne from May 2018 to March 2019 were included. A socio-demographic and food questionnaire was administered. Medical data were collected from the medical records. Blood and urine samples were taken. The descriptive analysis used Student and chi-squared tests. Results: A total of 341 women were included. The majority were born in Haiti (39%) and French Guiana (34%). At least one micronutrient deficiency was observed in 81% of women. Precarious women had a significantly greater risk of micronutrient deficiency during pregnancy compared to those with both normal and complementary health insurance. Conclusions: Micronutrient deficiencies in pregnant women in French Guiana are a public health problem, a fact that was previously overlooked in the context of rising obesity. With over half the women overweight or obese, and 81% with at least 1 micronutrient deficiency, balanced nutrition should be a major focus.
, Maria Biörklund-Helgesson, Kristina Andersson-Stefanovic, Anders Lareke, Olof Böök, Christina Skjöldebrand
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5635

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Background: An adequate dietary intake, especially of protein and energy, is important for maintaining health among elderly people, especially those in care homes. One strategy to ensure nutritional intake is to customise attractive products through enrichment to match the needs of elderly people in care homes. Objective: To evaluate liking and practical aspects of protein and energy enriched in-between meals designed for elderly people in care homes through the use of quantitative and qualitative assessments. Design: A broad range of energy and protein enriched in-between meals, including both savoury and sweet products, were included. The products were evaluated by a consumer test and a focus group discussion with elderly respondents. The products were also evaluated by a second focus group discussion with care staff. Results: The most liked products were ice cream and cheesecake. All products achieved high scores for appearance, taste/flavour and texture. No product included in the study was extremely disliked. However, the least liked product was tomato soup, which scored above the middle of the scale except for texture. It was clear from the focus group discussions that a colourful appearance, small portion size and texture were of primary importance. The temperature had an impact on liking and swallowability. Discussion: Most products were perceived by the elderly participants as appealing and tasting good, and possible to include in a daily diet. It was clear that the colours of the foods were of primary importance. In line with other studies, it was found that highly liked in-between meals were frozen, cold and sweet. These products were also easy to swallow. Conclusions: It is possible to produce highly liked energy and protein enriched in-between meal products designed for elderly people. The temperature had a great impact on the liking of texture, taste and flavour. In-between meals should preferably be colourful and have a small portion size.
, Iii Victor L. Fulgoni
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5618

Abstract:
Mushrooms are part of vegetables and are important source of nutrients and bioactive compounds. The objective was to assess the nutritional impact of adding a serving of mushrooms in USDA Food Patterns using a similar approach to that used by USDA for Dietary Guidelines. A composite of commonly consumed raw mushrooms (white, brown/crimini and portabella; at 1:1:1 ratio) and raw speciality mushrooms (oyster mushrooms) were used for modeling. The United States Department of Agriculture (USDA) Food Data central database (https://fdc.nal.usda.gov/) was used to obtain nutrient profiles of mushrooms. Nutritional profiles of USDAs Food Patterns were obtained from the Scientific Report of the 2015 Dietary Guidelines Advisory Committee, Appendix E-3 (https://health.gov/dietaryguidelines/ 2015-scientific-report/15-appendix-E3/) and dietary modeling was accomplished by adding nutrients from mushrooms. Addition of an 84 g serving of commonly consumed raw mushrooms to USDA Food Patterns resulted in about 1% increase in calories, less than 5% increase in macronutrients, 2–3% increase in fiber, 8–12% increase in potassium, 12–18% increase in riboflavin, 11–26% increase in niacin, 11–23% selenium and 16–26% increase in copper depending upon the pattern type and calorie level. Mushrooms exposed to UV light to increase vitamin D levels to 200 IU/serving also increased vitamin D by 67–90% in USDA Food Patterns. Addition of oyster mushroom also additionally increased 8–11% vitamin D and 10–16% choline in USDA Food Patterns. Addition of mushrooms had minimal effect on sodium (1% or less increase) and no effect on saturated fat or cholesterol in USDA Food Patterns. Based on published data, a serving of commonly consumed mushrooms would also be expected to add 2.2 mg ergothioneine and 3.5 mg glutathione to the USDA Food Patterns. Addition of mushrooms to USDA Food Patterns increased several micronutrients including shortfall nutrients (such as potassium, vitamin D and choline), and had a minimal or no impact on overall calories, sodium or saturated fat.
Yuehua Wang, Wenwen Gu, Fuguang Kui, Fan Gao, Yuji Niu, Wenwen Li, Yaru Zhang, Zhenzhen Guo, Gangjun Du
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5623

Abstract:
Background: Coronavirus disease 2019 (COVID-19) outbreak is progressing rapidly, and poses significant threats to public health. A number of clinical practice results showed that traditional Chinese medicine (TCM) plays a significant role for COVID-19 treatment. Objective: To explore the active components and molecular mechanism of semen armeniacae amarum treating COVID-19 by network pharmacology and molecular docking technology. Methods: The active components and potential targets of semen armeniacae amarum were retrieved from traditional Chinese medicine systems pharmacology (TCMSP) database. Coronavirus disease 2019-associated targets were collected in the GeneCards, TTD, OMIM and PubChem database. Compound target, compound- target pathway and medicine-ingredient-target disease networks were constructed by Cytoscape 3.8.0. Protein-protein interaction (PPI) networks were drawn using the STRING database and Cytoscape 3.8.0 software. David database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The main active components were verified by AutoDock Vina 1.1.2 software. A lipopolysaccharide (LPS)-induced lung inflammation model in Institute of Cancer Research (ICR) mice was constructed and treated with amygdalin to confirm effects of amygdalin on lung inflammation and its underlying mechanisms by western blot analyses and immunofluorescence. Results: The network analysis revealed that nine key, active components regulated eight targets (Protooncogene tyrosine-protein kinase SRC (SRC), interleukin 6 (IL6), mitogen-activated protein kinase 1 (MAPK1), mitogen- activated protein kinase 3 (MAPK3), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), HRAS proto-oncogene (HRAS), caspase-3 (CASP3)). Gene ontology and KEGG enrichment analysis suggested that semen armeniacae amarum plays a role in COVID- 19 by modulating 94 biological processes, 13 molecular functions, 15 cellular components and 80 potential pathways. Molecular docking indicated that amygdalin had better binding activity to key targets such as IL6, SRC, MAPK3, SARS coronavirus-2 3C-like protease (SARS-CoV-2 3CLpro) and SARS-CoV-2 angiotensin converting enzyme II (ACE2). Experimental validation revealed that the lung pathological injury and inflammatory injury were significantly increased in the model group and were improved in the amygdalin group. Conclusion: Amygdalin is a candidate compound for COVID-19 treatment by regulating IL6, SRC, MAPK1 EGFR and VEGFA to involve in PI3K-Akt signalling pathway, VEGF signalling pathway and MAPK signalling pathway. Meanwhile, amygdalin has a strong affinity for SARS-CoV-2 3CLpro and SARS-CoV-2 ACE2 and therefore prevents the virus transcription and dissemination.
Wen-Cheng Fu, Hai-Yan Li, Tian-Tian Li, Kuo Yang, Jia-Xiang Chen, Si-Jia Wang, Chun-Hui Liu,
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.4527

Abstract:
Background: Saturated fatty acids (SFAs) generally have been thought to worsen insulin-resistance and increase the risk of developing type 2 diabetes mellitus (T2DM). Recently, accumulating evidence has revealed that SFAs are not a single homogeneous group, instead different SFAs are associated with T2DM in opposing directions. Pentadecanoic acid (C15:0, PA) is directly correlated with dairy products, and a negative association between circulating PA and metabolic disease risk was observed in epidemiological studies. Therefore, the role of PA in human health needs to be reinforced. Whether PA has a direct benefit on glucose metabolism and insulin sensitivity needs further investigation. Objective: The present study aimed to investigate the effect and potential mechanism of action of PA on basal and insulin stimulated glucose uptake in C2C12 myotubes. Methods: Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay. Cell membrane proteins were isolated and glucose transporter 4 (GLUT4) protein was detected by western blotting to examine the translocation of GLUT4 to the plasma membrane. The phosphorylation levels of proteins involved in the insulin and 5'-adenosine monophosphate-activated protein kinase (AMPK) pathways were examined by western blotting. Results: We found that PA significantly promoted glucose uptake and GLUT4 translocation to the plasma membrane. Mechanistically, PA had no effect on the insulin-dependent pathway involving insulin receptor substrate (Tyr632) and Akt, but increased phosphorylation of AMPK and Akt substrate of 160 kDa (AS160). Compound C (an AMPK inhibitor) blocked PA-induced AMPK activation and reversed PA-induced GLUT4 translocation, indicating that PA promotes glucose uptake via the AMPK pathway in vitro. Moreover, PA significantly promoted insulin-stimulated glucose uptake in myotubes. Under insulin stimulation, PA did not affect the insulin-dependent pathway, but still activated AMPK. Conclusion: PA, an odd-chain saturated fatty acid, significantly stimulates glucose uptake via the AMPK-AS160 pathway and exhibits an insulin-sensitizing effect in myotubes.
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