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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.
, 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

Abstract:
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

Abstract:
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

Abstract:
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

Abstract:
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

Abstract:
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

Abstract:
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

Abstract:
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

Abstract:
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

Abstract:
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.
Weijing Wu, Zaigui Li, Fei Qin,
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.4998

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Background: Tartary buckwheat has beneficial effects on glucose and lipid metabolism of patients with type 2 diabetes mellitus. However, the physiological effects of a soluble dietary fiber (SDF) from tartary buckwheat have rarely been studied, especially in vivo. Objective: This study aimed to examine the hypoglycemic and hypolipidemic effects of SDF from tartary buckwheat bran on high-fat diet/streptozotocin-induced diabetic mice. Design: The SDF of tartary buckwheat bran was collected according to the Association of Official Analytical Chemists method 991.43. Diabetic mice were treated with high-fat diets supplemented with 0.5, 1, and 2% SDF for 8 weeks. Parameters related to glucose and lipid metabolism and relevant mechanisms, including the excretion of short-chain fatty acids and the glycemic signaling pathway in the liver, were investigated. In addition, the structural characterization of a purified polysaccharide from SDF of tartary buckwheat bran was illustrated. Result: Supplementation with SDF in the diet resulted in reduced levels of fasting blood glucose, improved oral glucose tolerance, increased levels of liver glycogen and insulin, as well as improved lipid profiles in both the serum and liver, in diabetic mice. The amelioration of glucose and lipid metabolism by SDF was accompanied by an increase in the short-chain fatty acid levels in the cecum and co-regulated by hepatic adenosine- 5′-monophosphate-activated protein kinase (AMPK) phosphorylation. A neutral tartary buckwheat polysaccharide with an average molecular weight of 19.6 kDa was purified from the SDF, which consisted mainly of glucose with α-glycosidic bonds. Conclusions: The SDF of tartary buckwheat bran exhibits hypoglycemic and hypolipidemic effects in diabetic mice, contributing to the anti-diabetic mechanisms of tartary buckwheat.
, Jacqueline Maalouly, Elias Bou-Maroun, Nicolas Sok, Philippe Cayot, Maya Tueni
Food & Nutrition Research, Volume 65; https://doi.org/10.29219/fnr.v65.5556

Abstract:
Background: Plant-based foods such as hummus are alternative to animal protein, and when properly prepared, they help to alleviate nutritional iron deficiency that leads to anemia, a global health problem. Objective: The objective was to assess iron intake among Lebanese women and related participant’s characteristics, discern iron-rich dietary patterns, evaluate their association with nutrients intake and participant’s sociodemographic characteristics, and identify the women preparing hummus traditionally and properly for an enhanced iron bioavailability. Design: A cross-sectional study of 400 Lebanese women (18–74 years old) was conducted in Lebanon. Data from a questionnaire, including sociodemographic and health characteristics, dietary intake, and hummus preparation and consumption, were collected. Dietary data were obtained by a food frequency questionnaire and a 24-h recall. Dietary patterns were identified by principal component analysis. Linear regression and binomial logistic regression models were used to explore the association between the intake of dietary iron, its patterns, and the participants’ characteristics. Results: About 60% of the women had iron intake deficiency, especially with lower income (odds ratio [OR] = 1.88, 95% confidence interval [CI]: 1.107, 3.194). Four iron-rich dietary patterns were identified: legumes; organ/lunch meat and chicken; canned fish; and beef and hummus. The factor scores of the latter were positively correlated with protein, vitamin C, iron, folate, vitamin B12, and vitamin A with r = 0.195 and P < 0.01 for all. No significant difference was shown among the women’s sociodemographic characteristics for the consumption of the hummus-related pattern. Only 9.2 and 22.7% of the women considered proper preparation of chickpea and hummus, respectively, which significantly (P < 0.05) correlated with older women (66.7%). Discussion & Conclusion: The majority of the Lebanese women still have iron intake deficiency and the minority reported proper preparation of hummus. Intervention programs spreading awareness among Lebanese women are needed for encouraging adequate iron intake and considering proper steps to improve iron bioavailability from plant-based food.
Rui-Xing Zhang, Wen-Chao Zhu, Guo-Xin Cheng, Ya-Nan Yu, Quan-Hui Li, Saeed Ul Haq, Fazal Said,
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.3729

Abstract:
Background: Carotenoids, the secondary metabolites terpenoids, are the largest factors that form the fruit color. Similar to flavonoids, they are not only safe and natural colorants of fruits but also play a role as stress response biomolecules. Methods: To study the contribution of the key genes in carotenoids biosynthesis, fruit-color formation, and in response to cold stress, we characterized the key regulatory factor CaATHB-12 from the HD-ZIP I sub-gene family members in pepper. Results: Cold stress enhanced carotenoid accumulation as compared with the normal condition. CaATHB-12 silencing through virus-induced gene silencing changed the fruit color by regulating the carotenoid contents. CaATHB-12 silencing increased the antioxidant enzyme activities in the fruits of pepper, exposed to cold stress, whereas CaATHB-12 overexpression decreased the activities of antioxidant enzymes in the transgenic Arabidopsis lines, exposed to cold stress, suggesting that CaATHB-12 is involved in the regulation of cold stress in the pepper fruits. Conclusion: Our research will provide insights into the formation of fruit color in pepper and contribution of CaATHB-12 in response to cold stress. Further study should be focused on the interaction between CaATHB-12 and its target gene.
Honghan Ge, Tingting Yang, Jing Sun,
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.3920

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Background: Dietary factors play an important role in the development of depressive symptoms. Carotenoids have effective antioxidant and anti-inflammatory effects, but few studies have explored the associations between dietary carotenoid intake and depressive symptoms. Objective: To evaluate the association between dietary carotenoid intake and the risk of depressive symptoms in adults from the United States. Design: This cross-sectional study included adult participants from the National Health and Nutrition Examination Survey 2009–2016. Depressive symptoms were assessed using the Patients’ Health Questionnaire- 9. Intake of carotenoids was obtained through two 24-h dietary recall interviews. We applied logistic regression models and restricted cubic spline models to evaluate the associations of dietary alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein with zeaxanthin, and total carotenoid intake with the risk of depressive symptoms. Results: Overall, a total of 17,401 adults aged 18–80 years were included in this study. After adjustment for potential confounders, the odds ratios (95% confidence intervals) of depressive symptoms in the highest versus lowest quartiles were 0.71 (0.56–0.92) for alpha-carotene, 0.59 (0.47–0.75) for beta-carotene, 0.71 (0.55–0.92) for beta-cryptoxanthin, 0.66 (0.49–0.89) for lycopene, 0.50 (0.39–0.64) for lutein with zeaxanthin, and 0.59 (0.45–0.78) for total carotenoid intake. U-shaped dose–response relationships were found between both beta- carotene and lutein with zeaxanthin intake and the risk of depressive symptoms. Conclusion: Results suggest that alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein with zeaxanthin, and total carotenoid intake may be inversely associated with the risk of depressive symptoms in the U.S. adults.
Lei Jing, Baiwen Hu, Qing Hua Song
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.4208

Abstract:
Background: Obesity is closely related to osteoporosis. Lycium barbarum polysaccharides (LBPs) have anti- osteoporosis activity. Objective: This study aimed to explore the role of LBPs in palmitic acid (PA)-induced osteoblast apoptosis. Methods: The microarray data set GSE37676 was downloaded from Gene Expression Ominibus (GEO) database. Top 300 differentially expressed genes (DEGs) were used to construct a protein–protein interaction (PPI) network based on STRING database, and significant modules were analyzed and their key genes were screened by using Cytoscape software. COEXPEDIA database showed that there was co-expression between Chrdl1 and peroxisome proliferator-activated receptor (PPARγ). MC3T3-E1 cells were treated with 100–500 μg/mL of PA. Reverse transcription polymerase chain reaction (RT-PCR) and western blot assays were used to detect mRNA and protein levels. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were used to detect cell viability and cell apoptosis. Results: Chrdl1 was the key gene from the most significant module and downregulation in MC3T3-E1 cells treated with PA. MicroRNA miR-200b-3p and PPARγ were significantly upregulated among PA-treated MC3T3-E1 cells. The results of luciferase reporter gene assay showed that miR-200b-3p targeted Chrdl1 3’-UTR. Over-expressing miR-200b-3p promoted PA-induced cell apoptosis and inhibited cell viability. After pre-treating cells with PA and LBP, MC3T3-E1 cell apoptosis rate was relatively lower than that of mimics+PA200 group. Chrdl1 inhibition partly reversed miR-200b-3p effect on inhibiting apoptosis among MC3T3-E1 cells pre-treated with LBP and PA. Decreased C CASP3, PPARγ and increased Chrdl1 by miR- 200b-3p inhibition were partly reversed by Chrdl1 inhibition. Conclusions: LBPs inhibit PA-induced MC3T3-E1 cell apoptosis by mainly decreasing miR-200b-3p to upregulate Chrdl1, but miR-200b-3p/Chrdl1/PPARγ is not the only mechanism for LBPs protecting osteoblasts from PA.
Kung-Chi Chan, Kar-Eng Kok, Keh-Feng Huang, Yao-Lin Weng, Yun-Chin Chung
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.4272

Abstract:
Background: The antioxidant effects of Bacillus subtilis-fermented red bean (natto-red bean) extract (NRBE) in young (6 weeks old) Sprague–Dawley rats and aged (12 months old) mice had been reported previously. Objective: To evaluate the antioxidant and anti-inflammatory effects of NRBE in the kidneys of streptozocin- induced diabetic rats. Design: Normal control rats and diabetic rats were orally gavaged with saline and low-dose NRBE (100 mg/ kg body weight [BW]), medium-dose NRBE (200 mg/kg BW), and high-dose NRBE (500 mg/kg BW), for 12 weeks and then sacrificed. Concentration of fasting glucose, adiponectin, renal function markers, antioxidative markers, and pro-inflammatory markers were measured. Results: Oral administration of 50% ethanolic extract of NRBE with a dosage of 100 mg/kg BW, 200 mg/kg BW, or 500 mg/kg BW could improve the symptoms of kidney enlargement and renal function. Supplementation of NRBE can effectively inhibit the formation of renal reactive oxygen species and advanced-glycation end-products and increase renal glutathione content and serum adiponectin. A low dose of NRBE (100 mg/ kg BW) decreased fasting blood sugar and renal interleukin (IL)-6 expression. Serum C-reactive protein, renal tumor necrosis factor-α, and monocyte chemoattractant protein-1 concentrations were decreased, and renal superoxide dismutase activity was increased in the medium-dose NRBE group. Twenty-four hour creatinine clearance and urinary albumin excretion also improved by medium-dose NRBE supplementation. In NRBE, total phenols and flavonoids were 6.3 mg gallic acid equivalent/g and 12.02 mg rutin equivalent/g, respectively, and kampherol was the major active antioxidant compound. Conclusion: This study demonstrated that appropriate amount of NRBE, 200 mg/kg BW in rats, could prevent diabetic nephropathy by improving antioxidant status and inhibiting inflammation in renal tissue.
, Nobuko Murayama, Hiromi Ishida, Taeko Yamamoto, Sayaka Hazano, Akemi Nakanishi, Yumi Arai, Miho Nozue, Yukiko Yoshioka, Saori Saito, et al.
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.5377

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Background: Evidence for whether the nutrient intakes of Japanese schoolchildren differ according to household income is sparse. Objective: We investigated the role of school lunches for nutrient adequacy among Japanese primary school children using dietary reference intakes in a cross-sectional survey. Design: Participants were 10- to 11-year-old (5th grade) children from 19 public primary schools in four prefectures of East Japan, and 836 children were analyzed. The participants completed 24-h dietary records with photographs of their meals for 4 consecutive days, composed of 2 days with and 2 days without a school lunch. Children’s household income was obtained from questionnaires that were completed by the participants’ guardians and divided into the following three categories: low (0.2236–2.2361 million yen; n = 319), middle (2.3333–2.8868 million yen; n = 194), and high (3.1305–6.3640 million yen; n = 323). Logistic regression analyses were used to estimate the odds ratios for whether participants had poor nutrient intakes, with adjustment for confounders. Results: On days without a school lunch, the prevalence of nutrient shortages was significantly higher compared with those on days with a school lunch for most macro- and micronutrients among all three levels of household income. Children from low-income households had higher rates of nutrient shortages for vitamin B6, pantothenic acid, K, Mg, P, Fe, and Zn than those from middle-income households on days without a school lunch (P = 0.004, 0.001, 0.001, 0.006, 0.037, <0.001, and 0.015, respectively), but those differences were not significant on days with a school lunch. Conclusion: The findings suggest that school lunches are important for achieving adequate nutrient intakes in schoolchildren and reduce disparities of adequate nutrient intake by household income levels.
Rongrong Lu, Zicong Zheng, Yimin Yin,
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.3666

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Background: Diabetic osteoporosis has become a severe public health problem in the aging societies. Genistein has been reported to play an important role in preventing and treating metabolic diseases via its anti-inflammatory, antioxidant, anti-estrogenic, and estrogen-like functions. Objective: We aimed to investigate whether genistein exerts bone-protective effect on diabetic rats induced by 35 mg/kg streptozotocin (STZ) plus a 4-week high-fat diet. Design: Sprague–Dawley rats were randomly divided into four groups: (1) control group, (2) type 2 diabetes mellitus (T2DM) model group, (3) T2DM with 10 mg/kg genistein, and (4) T2DM with 30 mg/kg genistein. After an 8-week treatment with genistein, the femurs, tibias, and blood were collected from all rats for further analysis. Results: Genistein at 10 mg/kg showed little effect on diabetic osteoporosis, whereas genistein at 30 mg/kg significantly improved glucose and bone metabolisms compared with diabetic rats. Our results showed that 30 mg/ kg genistein significantly increased bone mineral density, serum osteocalcin, and bone alkaline phosphatase. Genistein also effectively lowered fasting blood glucose, tartrate-resistant acid phosphatase 5b, tumor necrosis factor-α, interleukin-6, and numbers of adipocytes and osteoclasts. Compared with the T2DM group, protein levels of receptor activator of nuclear factor κB ligand (RANKL) and peroxisome proliferator-activated receptor- γ (PPAR-γ) were decreased, while protein levels of osteoprotegerin (OPG), β-catenin, and runt-related transcription factor 2 (Runx-2) were increased after genistein intervention. Conclusion: Genistein could effectively improve abnormal bone metabolism in STZ-induced diabetic rats; the underlying molecular mechanisms might be related to OPG/RANKL, PPAR-γ, and β-catenin/Runx-2 pathways.
, Ali A Al-Qarni, Mohammed Al-Jamaan
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.4751

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Background: Food intake has important implications for patients with type 2 diabetes. Objective: Similarly, in other crop species, this observational study aimed to assess dietary carbohydrate (CHO) and non-starch polysaccharide (NSP) intake and examine their association with glycemic control among Saudi patients with type 2 diabetes mellitus (T2DM). Design: We investigated dietary intake in 404 patients (207 males and 197 females) with T2DM between November 2018 and March 2019. Dietary intake was assessed by face-to-face interviews using a validated dietary questionnaire. Results: The results revealed that dietary CHO intake (67% of energy) exceeded the recommended daily intake, and white rice (Basmati rice) was the major contributor to CHO intake. However, the dietary NSP intake was lower than recommended, and it was negatively associated with HbA1c levels. Conclusion: This cross-sectional study showed that dietary CHO intake was high among Saudi patients with type 2 diabetes, and that their daily intake of NSPs was correlated with a lower level of HbA1c. Dietary advice should be given for patients with diabetes to reduce their intake of starchy food such as rice.
Yang Li, Xin Jiang, Hongjian Xu, Jingyi Lv, Guangning Zhang, , Yonggen Zhang, Xiaoxiang Li
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.3649

Abstract:
Background: As a major disease affecting dairy cow production worldwide, bovine mastitis is caused by a variety of pathogenic microorganisms that eventually cause mammary gland inflammation. Acremonium terricola culture (ATC) is a new type of affordable feed additive produced by the solid fermentation of A. terricola isolated from Cordyceps gunnii and exerted its anti-inflammatory effect. Objectives: To evaluate the protective effects of ATC on mastitis and investigate its active mechanism, a lipopolysaccharide (LPS)-induced rat mastitis model was used in two experiments. Design: In Experiment 1, a total of 40 female Sprague–Dawley rats were used to determine the optimal supplementary dose of ATC via gavage trial. In Experiment 2, we examined the effects of an optimal dose of ATC on LPS-induced mastitis in rats. Results: The results of Experiment 1 showed that administration of ATC improved growth performance and antioxidant functions in the serum and the liver, as well as immunoglobulin A, G, and M levels in rat serum, and it decreased the content of alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein, and serum urea nitrogen in rat serum; a dosage of 250–1,250 mg/kg/day was shown to be high enough to be effective. The results of Experiment 2 indicated that ATC can relieve the inflammatory reaction of mammary glands in rats, and the LPS-induced expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, and inducible nitric oxide synthase significantly decreased after ATC treatment. Moreover, our results demonstrated that ATC markedly enhanced the activity of antioxidase in this rat mastitis model. The results of Western blot analysis revealed that ATC could suppress the expression of toll-like receptor 4, phosphorylation of extracellular signal-regulated kinase, and activity of c-Jun N-terminal kinase in the LPS-stimulated mastitis model. Conclusion: Taken together, ATC was shown to exert its anti-inflammatory effect by blocking mitogen-activated protein kinase signaling pathways. These results demonstrate that ATC exerts anti-inflammatory and antioxidant effects in mastitis prevention.
Jin Wang, Ping Li, Shuang Liu, Bowei Zhang, Yaozhong Hu, Hui Ma,
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.3672

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Background: In the past, most researchers paid more attention to the biological activity of tea infusion and tea polyphenols; however, the prebiotic role of tea leaf powder is still unknown. Green tea leaf powder is rich in dietary fiber and is suggested to be beneficial for human health. Only limited studies have looked at the effects of tea leaf powder (which mainly contains tea dietary fiber) on gut microbiota and health. Objective: The purpose of our study was to determine the effects of green tea leaf powder in preventing hyperlipidemia and to understand its potential lipid-lowering mechanism. Design: Mice in three treatment groups were fed high-fat diets (HFDs) by administering either 0.5, 1.0, or 2.0 g/kg•d dietary fiber-enriched green tea leaf powder of low, medium, or high, respectively, for 12 weeks. Serum biochemical analyses and mRNA gene expression levels of related energy and lipid metabolism biomarkers from the liver were investigated. In addition, 16S rRNA cecal microbiota and fecal short chain fatty acids (SCFAs) were tested. Results: Green tea leaf powder reduced body weight and total cholesterol of HFD-fed mice in a dose-dependent manner. Green tea leaf powder also increased satiety hormone secretion and reduced systemic inflammation of HFD-fed mice. Real-time polymerase chain reaction (PCR) analyses reconfirmed that green tea leaf powder prevented dyslipidemia by enhancing hepatic mRNA expression levels of peroxisome proliferator-activated receptor alpha, cholesterol 7a-hydroxylase, and Adenosine triphosphate (ATP)-binding cassette transporter A1 and decreasing the expression of fatty acid synthase, sterol regulatory element-binding protein 1c, and liver X receptor. Green tea leaf powder promoted the growth of Blautia, Oscillibacter, Ruminiclostridium, Alloprevotella, and Butyrivibrio and inhibited the growth of Erysipelatoclostridium, Desulfovibrio, and Candidatus_Saccharimonas in the cecum of HFD-fed mice. Conclusion: In summary, our results indicate that green tea leaf powder improves lipid metabolism of HFDfed mice in a dose-dependent manner. The potential mechanism involves a synergistic role in reprogramming gut microbiota, increasing satiety hormone secretion, and reducing systemic inflammation.
Wenli Huang, Guangqiang Wang, Yongjun Xia, Zhiqiang Xiong,
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.3751

Abstract:
Background: Non-alcoholic fatty liver disease (NAFLD) includes a range of liver diseases that occur in the absence of significant alcohol consumption. The probiotic bacterial strains Lactobacillus casei LC2W, which overexpresses the bile salt hydrolase (BSH) gene (referred to as pWQH01), and Lactobacillus plantarum AR113, which exhibits high BSH activity, have been shown to improve hepatic lipid accumulation and may lower cholesterol levels in vivo. These effects may be BSH-dependent, as L. casei LC2W without BSH activity did not exert these beneficial effects. Objective: This study aimed to investigate the effects of Lactobacillus with high BSH activity on cholesterol accumulation and lipid metabolism abnormalities in oleic acid (OA)- and cholesterol-induced HepG2 cell models, and to determine the mechanism underlying the effects. Design: A HepG2 cell model of OA-induced steatosis and cholesterol-induced cholesterol accumulation was developed. OA- and cholesterol-treated HepG2 cells were incubated with L. plantarum AR113, L. casei LC2W or L. casei pWQH01 for 6 h at 37°C with 5% CO2. Subsequently, a series of indicators and gene expressions were analysed. Results: Both L. plantarum AR113 and L. casei pWQH01 significantly reduced lipid accumulation, total cholesterol (TC) levels and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) mRNA expression relative to the control group, whereas L. casei LC2W had no similar effect. Additionally, exposure to L. plantarum AR113 or L. casei pWQH01 significantly reduced the expression of sterol regulatory element-binding protein 1c (SREBP-1c), Acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and tumour necrosis factor-α (TNF-α) andsignificantly increased the expression of 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPARα). Conclusion: Both L. plantarum AR113 and L. casei pWQH01 appear to improve steatosis in vitro in a BSH-dependent manner.
Qilin Zhang, Zhaosong Du, Yu Zhang, Ziming Zheng, Qiang Li, Kaiping Wang
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.4364

Abstract:
Background: Lentinus edodes is a medicinal mushroom widely used in Asian countries for protecting people against some types of cancer and other diseases. Objective: The objective of the present study was to investigate the direct antiproliferation activity and the antitumor mechanisms of water-extracted polysaccharide (WEP1) purified from L. edodes in H22 cells and H22-bearing mice. Design: The extraction, isolation, purification, and structure determination of the water-soluted L. edodes polysaccharide WEP1 were performed. The growth inhibitory effects of WEP1 on H22 cells and H22-bearing mice were determined by 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) method and animal studies. Flow cytometry, scanning electron microscopy, and laser scanning confocal microscopy were used to observe the morphological characteristics of apoptotic cells. The levels of intracellular reactive oxygen species (ROS) were detected by flow cytometry using 2’,7’-dichlorofluorescein-3’,6’-diacetate (DCFH-DA). Western blot was used to determine the expressions of cell cycle proteins and apoptosis-related proteins. Results: Results showed that WEP1 with a molecular weight of 662.1 kDa exhibited direct antiproliferation activity on H22 cells in a dose-dependent manner. In vivo, WEP1 significantly inhibited the growth of tumor at different doses (50, 100, and 200 mg/kg) and the inhibition rates were 28.27, 35.17, and 51.72%, respectively. Furthermore, morphological changes of apoptosis and ROS overproduction were observed in H22 cells by WEP1 treatment. Cell cycle assay and western blot analyses indicated that the apoptosis induction activity of WEP1 was associated with arresting cell cycle at G2/M phase and activating mitochondrial-apoptotic pathway. Besides, WEP1 disrupted the microtubule network accompanied by alteration of cellular morphology. Conclusion: Results suggested that the antitumor mechanisms of WEP1 might be related to arresting cell cycle at G2/M phase, inhibiting tubulin polymerization and inducing mitochondrial apoptosis. Therefore, WEP1 possibly could be used as a promising functional food for preventing or treating liver cancer.
Gyuok Lee, Jawon Shin, Ara Jo, Sojeong Lm, Mi-Ri Kim, Yunhee Shoi, Hyojeong Yun, Donghyuck Bae, Jaeyong Kim, Chul-Yung Choi
Food & Nutrition Research, Volume 64; https://doi.org/10.29219/fnr.v64.5233

Abstract:
Background: Climacterium is a series of physical and mental symptoms occurring in women and men due to decreased levels of sex hormones. Women lose the ability to become pregnant due to decreased ovarian estrogen production; the initial symptom being hot flushes. In addition, urogenital atrophy, sexual dysfunction, mood changes, and osteoporosis occur. Extracts of Stauntonia hexaphylla (SH) and Vaccinium bracteatum (VB) fruits, with a wide range of biological activities, are widely used in traditional herbal medicine. Objective: The purpose of this study was to investigate the mitigation of menopausal symptoms, such as hot flushes and postmenopausal osteoporosis after combinatorial treatment with SH and VB (SHVB) of ovariectomized (OVX) rats. Design: We measured the bone regenerative effect of SHVB on receptor activator of nuclear factor-κB (NF- κB) ligand-induced osteoclast differentiation in vitro and on ovariectomy-induced osteoporosis in vivo. We investigated the effect of SHVB in a rat model of menopausal hot flushes, in which the tail skin temperature increases following ovariectomy-induced rapid decline in estrogen levels. Results: SHVB inhibited osteoclast formation and tartrate-resistant acid phosphatase activity in primary mouse bone marrow-derived cells. In an estrogen deficiency-induced rat model, measurement of serum bone turnover factors showed that treatment with SHVB lowered the increased bone turnover. Additionally, SHVB decreased OVX-induced bone loss of the total femur. SHVB inhibited osteoclast differentiation, prevented bone mass reduction, and improved trabecular bone structure and biochemical markers in OVX-induced osteoporosis. In addition, administration of SHVB significantly ameliorated the changes in skin temperature in OVX rats. Conclusion: SHVB improved the symptoms of menopause. These results provide the foundation for developing SHVB as a natural substance to replace hormones in the future.
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