Food & Nutrition Research

Transportation of whey protein-derived peptides using Caco-2 cell model and identification of novel cholesterol-lowering peptides

Thu, 25 May 2023 12:42:24 -0700

Background: The increasing morbidity and mortality of cardiovascular disease have become a major factor in human death. Serum cholesterol is considered to be an important risk factor for inducing coronary heart disease, atherosclerosis and other cardiovascular diseases. To screen intestinal absorbable functional small peptides with cholesterol-lowering activity by enzymatic hydrolysis of whey protein and develop cholesterol-based functional food that may become a substitute for chemically synthesized drugs, providing new ideas for diseases caused by high cholesterol.

Objective: This study aimed to evaluate the cholesterol-lowering activity of intestinal absorbable whey protein-derived peptides hydrolyzed by alkaline protease, trypsin and chymotrypsin, respectively.

Method: The whey protein hydrolysates acquired by enzymatic hydrolysis under optimal conditions were purified by a hollow fiber ultrafiltration membrane with a molecular weight cutoff of 10 kDa. The fractions obtained by Sephadex G-10 gel filtration chromatography were transported through a Caco-2 cell monolayer. The transported peptides were detected in the basolateral aspect of Caco-2 cell monolayers using ultra- performance liquid chromatography-tandem mass spectrometry (UPLC-MS).

Results: His-Thr-Ser-Gly-Tyr (HTSGY), Ala-Val-Phe-Lys (AVFK) and Ala-Leu-Pro-Met (ALPM) were unreported peptides with cholesterol-lowering activity. The cholesterol-lowering activities of the three peptides did not change significantly during simulated gastrointestinal digestion.

Conclusion: This study not only provides theoretical support for the development of bioactive peptides that can be directly absorbed by the human body, but also provides new treatment ideas for hypercholesterolemia.

Diallyl trisulfide induces pro-apoptotic autophagy via the AMPK/SIRT1 signalling pathway in human hepatocellular carcinoma HepG2 cell line

Shuoshuo Sun, Xiyu Liu, Xiao Wei, Shaohong Zhang, Weimin Wang — Fri, 19 May 2023 23:40:36 -0700

Background: Liver cancer is associated with a high mortality rate worldwide. Hepatocellular carcinoma (HCC) constitutes a large proportion of primary liver cancers, and most of its alterations currently remain untreatable. Diallyl trisulfide (DATS), the main chemical constituent of allicin, affects tumour development by regulating cell apoptosis. Allicin-induced autophagy could contribute to apoptosis in HepG2 cells. We rigorously examined the autophagy-related mechanism of allicin-induced apoptosis in HepG2 cells. We treated HepG2 cells with DATS to explore the effect of DATS on pro-apoptotic autophagy in HepG2 cell lines and examine its specific molecular mechanism.

Methods: HepG2 cells were treated with various concentrations of DATS for 24 and 48 h. Subsequently, cell viability was measured using the cell counting kit-8 (CCK-8) assay and cell clone formation assay. The HepG2 cell apoptosis was measured using Hoechst 33258 staining and western blotting. Autophagy and the AMP-activated protein kinase (AMPK)/NAD-dependent deacetylase sirtuin-1 (SIRT1) signalling pathway were detected using western blotting.

Results: Our results indicated that DATS inhibited HepG2 cell growth. Moreover, the ability of DATS to promote apoptosis in HepG2 cells increased with increasing concentration. We verified the phenomenon of DATS-induced autophagy in HepG2 cells and demonstrated that DATS treatment upregulated the protein expression of LC3-II/I. By measuring the expression of potential autophagy stimulators, we documented that DATS could induce pro-apoptotic autophagy by activating the AMPK/SIRT1 signalling pathway.

Conclusion: DATS induced pro-apoptotic autophagy via the AMPK/SIRT1 signalling pathway in the human HCC HepG2 cell line. Our findings further implicate allicin as a potential therapeutic agent against liver tumours in clinical settings, providing a basis for combining allicin with an autophagy agonist for treating liver cancer.

Allium macrostemon whole extract ameliorates obesity-induced inflammation and endoplasmic reticulum stress in adipose tissue of high-fat diet-fed C57BL/6N mice

Juhae Kim, Joo-Yeon Lee, Choon Young Kim — Thu, 18 May 2023 14:00:39 -0700

Background: Obesity is a major risk factor for metabolic syndrome and a serious health concern worldwide. Various strategies exist to treat and prevent obesity, including dietary approaches using bioactive ingredients from natural sources.

Objective: This study aimed to investigate the anti-obesity effect of whole-plant Allium macrostemon (also called as long-stamen chive) extract (AME) as a potential new functional food.

Design: C57BL/6N mice were divided into three groups and fed either a control diet (CD), high-fat diet (HFD), or HFD with AME treatment (200 mg/kg BW daily) for 9 weeks. The mice in the CD and HFD groups were treated with vehicle control.

Results: AME supplementation reduced HFD-induced body weight gain, fat mass, and adipocyte size. AME suppressed peroxisome proliferator-activated receptor γ and fatty acid synthase mRNA expression, indicating reduced adipogenesis and lipogenesis in adipose tissue. In addition, AME lowered inflammation in adipose tissue, as demonstrated by the lower number of crown-like structures, mRNA, and/or protein expression of macrophage filtration markers, as well as pro-inflammatory cytokines, including F4/80 and IL-6. Endoplasmic reticulum stress was also alleviated by AME administration in adipose tissue. Several phenolic acids known to have anti-obesity effects, including ellagic acid, protocatechuic acid, and catechin, have been identified in AME.

Conclusion: By suppressing adipose tissue expansion and inflammation, AME is a potential functional food for the prevention and/or treatment of obesity and its complications.

Iodine concentration in tap water, mineral water, and coffee

Monica Hauger Carlsen, Ellen Kielland, Maria Wik Markhus, Lisbeth Dahl — Mon, 08 May 2023 08:04:26 -0700

Background: Sufficient iodine intake is important for thyroid function and, particularly, among women of reproductive age. Water is a universal component of the diet and could be an important source of iodine. Iodine concentration in drinking water varies geographically. It is therefore of nutritional interest to explore the variation and the contribution of iodine from water and beverages.

Objective: To analyze the iodine concentrations in tap water, mineral waters, and coffee from different regions of Norway.

Design: Samples of tap water were obtained from different regions of Norway. Six brands of mineral water and several samples of coffee brews were sampled. The iodine concentration was determined by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).

Results: Iodine concentration in tap water varied from below Limit of Quantification to 0.8 μg/100 mL. Five out of six brands of mineral water had low concentrations of iodine, and one brand had a concentration of 38 μg/100 mL. Iodine concentrations in black coffee brews were similar to the tap water. Adding milk or plant-based milk alternatives increased the iodine concentration.

Discussion: Overall, iodine concentrations in tap water were generally low; however, variations were observed both for inland and coastal regions. A trend was seen for higher iodine concentrations in coastal region compared with inland region. For the average habitual iodine intake in Norway, tap water may not contribute significantly. One brand of mineral water could have considerable impact on iodine intake. Coffee does not contribute substantially more to iodine intake than tap water, unless the brew is added with milk or plant-based milk alternatives that contain iodine.

Conclusion: This study adds new information about iodine dietary sources in Norway. While tap water and black coffee have limited impact due to generally low concentrations, one mineral water brand may contribute significantly to iodine intake.

Euonymus alatus (Thunb.) Siebold leaf extract enhanced immunostimulatory effects in a cyclophosphamide-induced immunosuppressed rat model

Wed, 19 Apr 2023 13:08:38 -0700

Background: Euonymus alatus (Thunb.) Siebold (EA) is a medicinal plant used in some Asian countries to treat various diseases, including cancer, hyperglycemia, diabetes, urticaria, dysmenorrhea, and arthritis. Owing to the wide range of pharmacological applications of EA, various roles of EA are being studied.

Objective: We evaluated the immune-enhancing effect of EA treatment in a cyclophosphamide (Cy)-induced immunosuppressed rat model.

Design: We analyzed the immune enhancement effect of EA on macrophages by western blotting. In addition, cell viability and natural killer (NK) cell activity were analyzed in splenocytes following EA treatment. For in vivo studies, analysis of weekly body weight, spleen weight, immune cell count, cytokine levels, and spleen histological findings was performed following EA administration in Cy-induced immunocompromised rats.

Results: EA significantly increased cell viability and phospho-nuclear factor-kappa B and phospho-extracellular signal-regulated kinase protein levels in the macrophages. EA significantly increased NK cell activity in splenocytes compared with the control group. In Cy-induced immunosuppressed rats, EA administration increased spleen tissue weight and the contents of leukocytes, lymphocytes, granulocytes, intermediate cells, and plasma cytokines (tumor necrosis factor-α and interferon-γ). In addition, improvement in the damaged spleen tissue was observed.

Conclusions: These findings confirm that EA exerts an immune-enhancing effect, thereby suggesting its potential as an immunostimulatory agent or functional food.

Evaluation and prioritization of food environment policies in Norway using the Healthy Food Environment Policy Index (Food-EPI)

Mon, 17 Apr 2023 13:00:50 -0700

Background: Government policies promoting healthier food environments can contribute to healthier diets and prevent obesity and diet-related non-communicable diseases.

Objective: To assess the level of implementation of internationally recommended food environment policies in Norway and establish prioritised actions to create healthier food environments.

Design: The Healthy Food Environment Policy Index (Food-EPI) was adapted to the Norwegian context. It comprised 45 good practice indicators of government food environment policy and infrastructure support. Systematically compiled evidence of relevant policies was verified by government officials and formed the basis for assessing the level of implementation of these policies compared against international best practice benchmarks. The assessment was done by a national non-government expert panel (n = 35). The experts thereafter proposed and prioritized policy actions for government implementation.

Results: Most indicators were rated at a medium or high degree of implementation in both the policy action (69%) and the infrastructure support (77%) components. No indicators were rated as having ‘none or very little implementation’. Among the 14 recommended policy actions, active use of price regulation to increase the price of unhealthy foods and decrease the price of healthy foods was the highest priority. Other top priorities were ensuring healthy food environments in public settings and introducing free school meals. Demonstrating knowledge-based and coherent political leadership in public health nutrition policies was the highest priority among the 11 recommended infrastructure support actions.

Conclusion: The overall policies in Norway to promote a healthy diet show a medium to high level of implementation. This study highlights that there is still room for additional improvements in Norwegian policies and infrastructure support to promote healthy food environments.

Adolescents’ attitudes, preferences and perceived behaviours regarding healthy eating and whole grains from a gender and health interest perspective

Anna Calvén, Karin Jonsson, Karin Wendin, Christel Larsson — Mon, 10 Apr 2023 22:29:55 -0700

Background: A healthy diet is important not only for the growth and development of the human body but also for the prevention of chronic diseases. However, most Swedish adolescents do not follow dietary recommendations, especially the intake of whole grain is very low. To create targeted conditions for healthy food choices amongst adolescents, comprehensive knowledge of factors related to adolescents’ unhealthy and healthy eating is needed.

Objective: To investigate adolescents’ attitudes, preferences and perceived behaviours regarding healthy eating, with a specific focus on whole grains and to evaluate differences between genders and between adolescents with higher versus lower health interest.

Design: A total of 1,178 Swedish adolescents responded to a questionnaire about their attitudes, preferences and perceived behabviours towards healthy eating and whole grains, and their general interest in nutrition and health. Results of girls and boys were compared, as well as adolescents with a higher versus lower health interest.

Results: Displays information about healthy eating among adolescents and a comprehensive set of factors that may affect their ability to eat healthier. Overall, adolescents had a positive attitude towards food and health, but less than half felt that they managed to eat healthy. The consumption of different whole grain products was low, although the willingness to eat healthier and more whole grain was high. The most reported barrier to healthy eating, as well as increasing whole grain intake, was the unavailability of tasty healthy products, taste being even more important for adolescents with a low health interest than those with a high interest. Whole grain consumption and factors increasing the willingness of whole grain consumption were most prominent not only in adolescents with high health interest but also in girls compared with boys.

Conclusion: The results show good potential to improve dietary habits amongst adolescents. Taste and availability of healthy products were rated the most important, whilst knowledge about the products’ healthiness was rated the least important, especially amongst those with low health interest. By focusing on the attitudes and preferences of adolescents, the effectiveness may increase of initiatives to improve their dietary habits.

Consumption of meat and dairy substitute products amongst vegans, vegetarians and pescatarians

Fri, 31 Mar 2023 14:03:44 -0700

Background: An increasing number of people adhere to plant-based diets, and the market for plant-based meat and dairy substitute products has been expanding rapidly.

Objective: To examine total intake of macronutrients and salt in a sample of Norwegian vegans, vegetarians and pescatarians; the consumption frequency of plant-based meat and dairy substitutes and raw ingredients used in these products; and the contribution to total macronutrient and salt intake from these products.

Design: A cross-sectional design using single 24-h dietary recall to assess the intake of macronutrients, salt and substitute products that the participants (n = 158 Norway residents [age 18–60 years]: vegans [n = 83]; vegetarians [n = 47]; pescatarians [n = 28]) consumed. The chi-square test with pairwise comparisons and the Kruskal-Wallis test with post hoc test were used to compare differences between diet groups. Macronutrient and salt intake were assessed relative to the Nordic Nutrition Recommendations (NNR).

Results: Dietary macronutrient intake fell within NNR recommendations, with a favourable distribution of fatty acids and high levels of dietary fibre. Most of the vegans (90%), vegetarians (68%) and pescatarians (64%) consumed meat or dairy substitutes. The main raw ingredient in the substitute products was soy, followed by oats and peas. Overall, substitute products contributed to 12% of total energy and 16% of total salt intake. The substitute products contributed to higher saturated fatty acid (SFA) intake amongst vegans (27% of total SFA intake) compared with vegetarians (10%) and pescatarians (8%). Moreover, substitute products contributed to higher protein intake in vegans (19%) compared with pescatarians (7%).

Conclusion: Most participants consumed meat or dairy substitute products, suggesting that these products are included regularly in Norwegian plant-based diets. Furthermore, substitute products may contribute to dietary fat, SFA and protein intake amongst vegans.

In vitro anti-hepatocellular carcinogenesis of 1,2,3,4,6-Penta-O-galloyl-β-D-glucose

Mon, 27 Mar 2023 06:53:13 -0700

Background: 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (β-PGG) is a polyphenol ellagic compound with a variety of pharmacological effects and has an inhibitory effect on lots of cancers.

Objective: To explore the antitumor effects and mechanism of 1,2,3,4,6-Penta-O-galloyl-β-D-glucose on human hepatocellular carcinoma HepG2 cells.

Design: A network pharmacology method was first used to predict the possible inhibition of hepatocellular carcinoma growth by 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (β-PGG) through the p53 signaling pathway. Next, the Cell Counting Kit (CCK-8) assay was performed to evaluate changes in the survival rate of human hepatocellular carcinoma HepG2 cells treated with different concentrations of the drug; flow cytometry was used to detect changes in cell cycle, apoptosis, mitochondrial membrane potential (MMP) and intracellular Ca2+ concentration; real-time fluorescence quantification and immunoblotting showed that the expression of P53 genes and proteins associated with the p53 signaling pathway was significantly increased by β-PGG treatment.

Reasult: It was found that β-PGG significantly inhibited survival of HepG2 cells, promoted apoptosis, decreased MMP and intracellular Ca2+ concentration, upregulated P53 gene and protein expression, increased CASP3 expression, and induced apoptosis in HepG2 cells.

Conclusion: This study has shown that network pharmacology can accurately predict the target of β-PGG’s anti-hepatocellular carcinoma action. Moreover, it was evident that β-PGG can induce apoptosis in HepG2 cells by activating the p53 signaling pathway to achieve its anti-hepatocellular carcinoma effect in vitro.

Lactobacillus plantarum LP45 inhibits the RANKL/OPG signaling pathway and prevents glucocorticoid-induced osteoporosis

Xiaofeng Jiang , Xiaojun Qi , Chao Xie — Fri, 24 Mar 2023 00:00:00 -0700

Objective: To examine the potential effect of the probiotic strain Lactobacillus plantarum LP45 on osteoporosis and to explore the involved molecular mechanisms.

Methods: A rat model of glucocorticoid-induced osteoporosis (GIO) was established, which was also orally administered with increasing doses of LP45 for 8 weeks. After the termination of the 8-week treatment, the tibia and femur bones of rats were analyzed for bone histomorphometry, bone mineral content (BMC), and bone mineral density (BMD). Femoral biomechanics were assessed. In addition, levels of osteocalcin, tartrate-resistant acid phosphatase 5 (TRAP5), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) in the serum and bone marrow were also measured using ELISA, Western blot, and real time-polymerase chain reaction.

Results: GIO caused obvious defects in tibia and femur bone structures, in terms of tissue/bone volume, trabecular separation, trabecular thickness, and trabecular number, which could be rescued by LP45 dose dependently. The GIO-induced reductions in BMC, BMD, osteoblast surfaces per bone surface (BS), as well as elevated osteoclast surface per BS were largely restored by LP45 administration dose-dependently. LP45 also increased femoral biomechanics of GIO rats. Importantly, LP45 dose-dependently restored the changes of osteocalcin, TRAP5, OPG, and RANKL in the serum as well as bone marrow of GIO rats.

Conclusion: Oral LP45 administration could significantly prevent bone defects in GIO rats, suggesting its potential as a dietary supplement with beneficial effects against osteoporosis, which might involve the RANKL/OPG signaling pathway.

Garcinia cambogia water extract alleviates insulin resistance and hepatic lipid accumulation in mice fed a high-fat diet

Tue, 14 Mar 2023 12:22:08 -0700

Background: Garcinia cambogia is widely used as a weight-loss supplement, and it is reported to be negatively associated with metabolic diseases including insulin resistance (IR), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and dyslipidemia.

Objective: This study aimed to investigate the effect of G. cambogia water extract (GE) on high-fat diet (HFD)-induced obesity, IR, and hepatic lipid accumulation.

Design: C57BL/6 male mice were fed HFD with or without GE, GED and GEP for 16 weeks, and the mice were subjected to insulin tolerance tests and liver histological analysis. The hydroxycitric acid (HCA) levels of GE, GED, and GEP were measured by high-performance liquid chromatography.

Results: The results showed that GE significantly reduced HFD-induced body weight gain (P < 0.001), alleviated IR (P < 0.01), reduced serum total cholesterol (TC) (P < 0.001), and attenuated HFD-induced hepatic lipid accumulation. To investigate the constituent that was responsible for these effects, we separated GE into the component that dissolved in ethanol (GED) and the component that was precipitated by ethanol (GEP). Further mouse experiments showed that both GED and GEP were effective, but GED (which was used at a dose of 4 g/L) was more effective than GEP (which was used at a lower dose of 1 g/L). The HCA levels in GED and GEP were similar, although less than in GE. HCA may be the effective component in GE.

Conclusion: This study provides evidence that G. cambogia can be used as a natural supplement to alleviate IR and hepatic lipid accumulation.

Can vitamin D status influence the effect of stress on planning and problem-solving? A randomized control trial

Mon, 13 Mar 2023 12:14:27 -0700

Background: Nutritional interventions may serve as a stress resilience strategy with important implications for human health.

Objective: The aim of this study was to investigate the effect of vitamin D supplementation throughout wintertime on problem-solving and planning abilities during stressful circumstances.

Design: A total of 77 male inpatients with a mean age of 48 years (range 31–81) and stress-related mental health disorders were randomly assigned into a Vitamin D supplement group (daily intake of 40 μg) or a placebo supplement group (Control) (daily intake of 120 mg olive oil). The intervention period was from January 2018 to May 2018. The means and standard deviations for vitamin D status (25-hydroxyvitamin D3, nmol/L), pre- and post-test, respectively, were 58(21) and 46(15) for the Control group, and 63(18) and 76(21) for the Vitamin D group. Problem-solving and planning abilities were measured by the Tower of London (ToL) task pre- (midwinter) and post- (spring) supplement intervention. The ToL task was performed during exposure to distracting noise.

Results: The results revealed that vitamin D supplementation throughout the winter had a significant effect on number of correct responses on easier (1 and 2 move) ToL problems during stress; the Vitamin D group improved significantly from pre- to post-test, whereas the Control group did not. In addition, the Vitamin D group had significantly more correct responses than the Control group on post-test. The improved performance was not related to a speed-accuracy trade off effect; both groups showed significantly decreased planning times from pre- to post-test. The intervention did not differentially affect task performance on the more difficult (3 to 5 move) ToL problems. For the more demanding problems, IQ seemed to explain most of the variance regarding accuracy. Age explained most of the variance associated with task planning time.

Conclusion: Vitamin D supplementation seemed to improve resilience to stress, but it was limited to performance of easier tasks

Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytes

Haiwen Li, Ahmed Reza Rafie, Anwar Hamama, Rafat A. Siddiqui — Thu, 02 Mar 2023 13:17:12 -0800

Background: Obesity is the underlying risk factor for major metabolism complications, including non-alcoholic-fatty liver disease, atherosclerosis, and cardiovascular disease. The adipose tissue is a vital endocrine organ that plays a role in the synthesis and storage of lipid and, therefore, is a contributory factor to the development and progression of obesity. A growing interest in nutraceuticals suggests that natural products can alleviate the risk factors and may be effective in mitigating obesity.

Aim: The objective of this study was to examine the underlying mechanisms of immature ginger on adipocyte differentiation and lipogenesis in a 3T3-L1 cellular model.

Methods: Ginger samples, extracted in 80% methanol, were dried and resuspended in DMSO at 50 μg/mL as stock solution. For analysis, the extracted samples were further diluted in media. Effects on adipogenesis were evaluated by determining lipid droplet and triglyceride accumulation, whereas effects on lipogenesis were determined by measuring triglyceride contents and fatty acid profile. The expression of key regulatory genes involved in adipogenesis and lipogenesis was also determined.

Results: Our data indicate that the intracellular lipid accumulation decreased significantly by 15 or 25% on treatment with 25 or 50 μg/mL of ginger extract. Consistent with these data, significantly reduced triglyceride levels by 30 or 50% were observed on 25 or 50 μg/mL treatment with ginger extracts, respectively. In addition, ginger treatment significantly inhibited the differentiation-induced de novo lipogenesis and Δ9 desaturase activity. Furthermore, ginger treatment reduced adipogenesis genes, C/ebpβ and C/ebpδ, expression by 47 or 64%, respectively, but significantly increased Pparγ expression by 60% and adiponectin by 75%. Ginger extracts had no effect on Fas genes but reduced lipogenesis genes, acyl CoA carboxylase (Acc) expression by two-fold, and phosphoenolpyruvate carboxy kinase 1 (Pepck1) expression by 50%.

Conclusion: Our findings suggest immature ginger can potentially inhibit lipogenesis pathways by limiting the channeling of glucose carbon in fatty acid synthesis by inhibiting the expression of ACC and glycerol production via inhibiting the expression of PEPCK, which consequently inhibits triglyceride formation.

Inositol hexaphosphate promotes intestinal adaptation in short bowel syndrome via an HDAC3-mediated epigenetic pathway

Thu, 02 Feb 2023 05:20:39 -0800

Background: Short bowel syndrome (SBS) has high morbidity and mortality rates, and promoting intestinal adaptation of the residual intestine is a critical treatment. Dietary inositol hexaphosphate (IP6) plays an important role in maintaining intestinal homeostasis, but its effect on SBS remains unclear. This study aimed at investigating the effect of IP6 on SBS and clarified its underlying mechanism.

Methods: Forty male Sprague–Dawley rats (3-week-old) were randomly assigned into four groups (Sham, Sham + IP6, SBS, and SBS + IP6 groups). Rats were fed standard pelleted rat chow and underwent resection of 75% of the small intestine after 1 week of acclimation. They received 1 mL IP6 treatment (2 mg/g) or sterile water daily for 13 days by gavage. Intestinal length, levels of inositol 1,4,5-trisphosphate (IP3), histone deacetylase 3 (HDAC3) activity, and proliferation of intestinal epithelial cell-6 (IEC-6) were detected.

Results: IP6 treatment increased the length of the residual intestine in rats with SBS. Furthermore, IP6 treatment caused an increase in body weight, intestinal mucosal weight, and IEC proliferation, and a decrease in intestinal permeability. IP6 treatment led to higher levels of IP3 in feces and serum, and higher HDAC3 activity of the intestine. Interestingly, HDAC3 activity was positively correlated with the levels of IP3 in feces (r = 0.49, P = 0.01) and serum (r = 0.44, P = 0.03). Consistently, IP3 treatment promoted the proliferation of IEC-6 cells by increasing HDAC3 activity in vitro. IP3 regulated the Forkhead box O3 (FOXO3)/Cyclin D1 (CCND1) signaling pathway.

Conclusion: IP6 treatment promotes intestinal adaptation in rats with SBS. IP6 is metabolized to IP3 to increase HDAC3 activity to regulate the FOXO3/CCND1 signaling pathway and may represent a potential therapeutic approach for patients with SBS.

Inhibition of castration-resistant prostate cancer growth by genistein through suppression of AKR1C3

Xiaoping Yu, Jiali Yan, Yulu Li, Jing Chen, Lujie Zheng, Tianyu Fu, Yanfeng Zhu — Tue, 31 Jan 2023 00:00:00 -0800

Background: Prostate cancer is the second leading cause of cancer-related death among males in America. The patients’ survival time is significantly reduced after prostate cancer develops into castration-resistant prostate cancer (CRPC). It has been reported that AKR1C3 is involved in this progression, and that its abnormal expression is directly correlated with the degree of CRPC malignancy. Genistein is one of the active components of soy isoflavones, and many studies have suggested that it has a better inhibitory effect on CRPC.

Objective: This study aimed to investigate the antitumor effect of genistein on CRPC and the potential mechanism of action.

Design: A xenograft tumor mouse model established with 22RV1 cells was divided into the experimental group and the control group, and the former was given 100 mg/kg.bw/day of genistein, with 22RV1, VCaP, and RWPE-1 cells cultured in a hormone-free serum environment and treated with different concentrations of genistein (0, 12.5, 25, 50, and 100 μmol/L) for 48 h. Molecular docking was used to elucidate the molecular interactions between genistein and AKR1C3.

Results: Genistein inhibits CRPC cell proliferation and in vivo tumorigenesis. The western blot analysis confirmed that the genistein significantly inhibited prostate-specific antigen production in a dose-dependent manner. In further results, AKR1C3 expression was decreased in both the xenograft tumor tissues and the CRPC cell lines following genistein gavage feeding compared to the control group, with the reduction becoming more obvious as the concentration of genistein was increased. When the genistein was combined with AKR1C3 small interfering ribonucleic acid and an AKR1C3 inhibitor (ASP-9521), the inhibitory effect on the AKR1C3 was more pronounced. In addition, the molecular docking results suggested that the genistein had a strong affinity with the AKR1C3, and that it could be a promising AKR1C3 inhibitor.

Conclusion: Genistein inhibits the progression of CRPC via the suppression of AKR1C3.

A proprietary blend of Sphaeranthus indicus flower head and Mangifera indica bark extracts increases muscle strength and enhances endurance in young male volunteers: a randomized, double-blinded, placebo-controlled trial

Meher Prasanna Rokkam, Olos Gora, Manikyeswara Rao Konda, Ajay Koushik — Fri, 27 Jan 2023 14:14:05 -0800

Background: The demand for safe and efficacious botanical formulations to increase muscle mass, strength, and stamina is increasing among athletes and the general population. The nutraceutical supplements of medicinal plant origin exert minimal health concern.

Objective: This randomized, double-blind, placebo-controlled study was aimed to evaluate the ergogenic potential of a proprietary, standardized formulation (LI12542F6) of Sphaeranthus indicus flower head and Mangifera indica stem bark extracts.

Methods: Forty male participants 18–40 years of age were assigned to receive either a placebo (n = 20) or 650 mg/day LI12542F6 (n = 20) for 56 days. All participants performed a fixed set of resistance exercises during the intervention. The primary endpoint was the change from baseline muscle strength, assessed by one-repetition maximum (1-RM) bench and leg presses, and handgrip strength. The secondary endpoints included cable pull-down repetitions, time to exhaustion on a treadmill, mid-upper arm circumference (MUAC), body composition using dual-energy x-ray absorptiometry (DEXA), and free testosterone and cortisol levels in serum.

Results: Fifty-six days supplementation of LI12542F6 significantly improved baseline bench press (P < 0.0001), leg press (P < 0.0001), handgrip strength (P < 0.0006), number of repetitions (P < 0.0001), and time to exhaustion (P < 0.0008), compared to placebo. Post-trial, the LI12542F6 group also showed significantly increased MUAC and improved body composition and serum hormone levels. The participants’ hematology, clinical chemistry, and vital signs were within the normal range. No adverse events were observed.

Conclusion: This study demonstrates that LI12542F6 supplementation significantly increases muscle strength and size and improves endurance in healthy men. Also, LI12542F6 is well-tolerated by the participants.

The clinicians’ view of food-related obstacles for treating eating disorders: A qualitative study

Billy Langlet, Maria Nyberg, Karin Wendin, Modjtaba Zandian — Wed, 25 Jan 2023 10:08:34 -0800

Background: Good health requires healthy eating. However, individuals with eating disorders, such as anorexia nervosa, require treatment to modify their dietary behaviours and prevent health complications. There is no consensus on the best treatment practices and treatment outcomes are usually poor. While normalising eating behaviour is a cornerstone in treatment, few studies have focused on eating and food-related obstacles to treatment.

Objective: The aim of the study was to investigate clinicians’ perceived food-related obstacles to treatment of eating disorders (EDs).

Design: Qualitative focus group discussions were conducted with clinicians involved in eating disorder treatment to get an understanding of their perceptions and beliefs regarding food and eating among eating disorder patients. Thematic analysis was used to find common patterns in the collected material.

Results: From the thematic analysis the following five themes were identified: (1) ideas about healthy and unhealthy food, (2) calculating with calories, (3) taste, texture, and temperature as an excuse, (4) the problems with hidden ingredients and (5) the challenges of extra food.

Discussion: All identified themes showed not only connections to each other but also some overlap. All themes were associated with a requirement of control, where food may be perceived as a threat, with the effects of food consumption resulting in a perceived net loss, rather than a gain. This mindset can greatly influence decision making.

Conclusions: The results of this study are based on experience and practical knowledge that could improve future ED treatments by enhancing our understanding the challenges certain foods pose for patients. The results may also help to improve dietary plans by including and explaining challenges for patients at different stages of treatment. Future studies could further investigate the causes and best treatment practices for people suffering from EDs and other eating disturbances.

Seed-derived peptide lunasin suppressed breast cancer cell growth by regulating inflammatory mediators, aromatase, and estrogen receptors

Chia-Chien Hsieh, Chi-Hao Wu, Shih-Han Peng, Chia-Hsin Chang — Wed, 25 Jan 2023 10:51:02 -0800

Background: Breast cancer is one of the most prevalent cancers in women. Its pathology comprises tumor cells and nearby stromal cells, accompanied by cytokines and stimulated molecules, resulting in a favorable microenvironment for tumor progression. Lunasin is a seed peptide with multiple bioactivities derived from seeds. However, the chemopreventive effect of lunasin on different characteristics of breast cancer has not been fully explored.

Objective: This study aims to explore the chemopreventive mechanisms of lunasin through inflammatory mediators and estrogen-related molecules in breast cancer cells.

Design: Estrogen-dependent MCF-7 and independent MDA-MB-231 breast cancer cells were used. The β-estradiol was used to mimic physiological estrogen. The gene expression, mediator secretion, cell vitality, and apoptosis impacting breast malignancy were explored.

Results: Lunasin did not affect normal MCF-10A cell growth but inhibited breast cancer cell growth, increased interleukin (IL)-6 gene expression and protein production at 24 h, and decreased its secretion at 48 h. In both breast cancer cells, aromatase gene and activity and estrogen receptor (ER)α gene expression were decreased by lunasin treatment, while ERβ gene levels were significantly increased in MDA-MB-231 cells. Moreover, lunasin decreased vascular endothelial growth factor (VEGF) secretion and cell vitality and induced cell apoptosis in both breast cancer cell lines. However, lunasin only decreased leptin receptor (Ob-R) mRNA expression in MCF-7 cells. Additionally, β-estradiol increased MCF-7-cell proliferation but not the proliferation of other cells; in particular, lunasin still inhibited MCF-7-cell growth and cell vitality in the presence of β-estradiol.

Conclusion: Seed peptide lunasin inhibited breast cancer cell growth by regulating inflammatory, angiogenic, and estrogen-related molecules, suggesting that lunasin is a promising chemopreventive agent.

The PPARα/CYP4A14 bile acid pathway is associated with lipid metabolism disorders caused by low birth weight with high-fat diet

Fei Zhou, Linquan Yang, Wenwen Sun, Xing Wang, Na Guo, Huijuan Ma, Linlin Yang — Tue, 24 Jan 2023 14:13:31 -0800

Purpose: To investigate possible mechanisms underlying the greater susceptibility of lipid metabolism disorders in low birth weight (LBW) mice fed with high-fat diets (HFDs).

Methods: LBW mice model was established by using the pregnancy malnutrition method. Male pups were selected from LBW and normal-birth weight (NBW) offspring at random. After 3 weeks of weaning, all offspring mice were fed with HFD. Serum triglycerides (TGs), cholesterol (TC), low density lipoprotein (LDL-C), total bile acid (TAB), non-esterified fatty acid (NEFA), and mice fecal bile acid profiles were measured. Lipid deposition in liver sections was visualized by Oil Red O staining. The weight ratio of liver, muscle, and adiposity was calculated. Tandem mass tag (TMT) combined with LC-MS/MS was used to determine the differentially expressed proteins (DEPs) of liver tissue in two groups. Bioinformatics was used for further analysis of DEPs to screen key target proteins, and then Western Blot (WB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to validate the expressions of DEPs.

Results: LBW mice fed with HFD showed more severe lipid metabolism disorders in the childhood. In contrast to the NBW group, the serum bile acids and fecal ω-muricholic acid (ω-MCA) levels in the LBW group were significantly lower. LC-MS/MS analysis showed that downregulated proteins were associated with lipid metabolism, and further analysis found that these proteins are mainly concentrated in peroxisome proliferation-activated receptor (PPAR) and primary bile acid synthesis signaling pathways and are involved in cellular processes and metabolic processes through binding and catalytic functions. Bioinformatics analysis indicated that the level of Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1), PPARα, key factors of cholesterol metabolism and bile acid synthesis, as well as downstream molecules Cytochrome P450 Family 4 Subfamily A Member 14 (CYP4A14), and Acyl-Coenzyme A Oxidase 2 (ACOX2) are markedly different in the liver of LBW individuals fed with HFD, and confirmed by WB and RT-qPCR.

Conclusion: LBW mice are more prone to dyslipidemia probably due to downregulated bile acid metabolism-related PPARα/CYP4A14 pathway, resulting in insufficient metabolism of cholesterol to bile acids, which, in turn, leads to elevated blood cholesterol.

Animal versus plant-based protein and risk of cardiovascular disease and type 2 diabetes: a systematic review of randomized controlled trials and prospective cohort studies

Tue, 28 Mar 2023 13:07:49 -0700

Objectives: To systematically review the evidence on the effect of replacing the intake of animal protein with plant protein on cardiovascular disease (CVD) and type 2 diabetes (T2D) and their intermediate risk factors.

Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 12th May 2022 for randomized controlled trials (RCTs) or prospective cohort studies that investigated replacement of animal protein with plant protein from foods. Outcomes were CVDs, T2D, and in RCTs also the effects on blood lipids, glycemic markers, and blood pressure. Risk of bias was evaluated with the Cochrane’s RoB2, ROBINS-I, and USDA’s RoB-NObS tools. Random-effects meta-analyses assessed the effects of plant vs. animal proteins on blood lipids in RCTs. The evidence was appraised according to the World Cancer Research Fund’s criteria.

Results: After screening 15,090 titles/abstracts, full text of 124 papers was scrutinized in detail, from which 13 RCTs and seven cohort studies were included. Eight of the RCTs had either some concern or high risk of bias, while the corresponding evaluation of cohort studies resulted in moderate risk of bias for all seven. Meta-analyses of RCTs suggested a protective effect on total cholesterol (mean difference -0.11 mmol/L; 95% CI -0.22, -0.01) and low-density lipoprotein cholesterol (-0.14 mmol/L; 95% CI -0.25, -0.02) by replacing animal protein with plant protein. The substitution of animal protein with plant protein (percentage of energy intake) in cohort studies was associated with lower CVD mortality (n = 4) and lower T2D incidence (n = 2). The evidence was considered limited-suggestive for both outcomes.

Conclusion: Evidence that the substitution of animal protein with plant protein reduces risk of both CVD mortality and T2D incidence is limited-suggestive. Replacing animal protein with plant protein for aspects of sustainability may also be a public health strategy to lower the risk of CVD mortality and T2D.

Dietary fiber and growth, iron status and bowel function in children 0–5 years old: a systematic review

Mon, 27 Mar 2023 09:27:23 -0700

Background: While dietary fiber intake is low in many children, the current trend to plant-based diets is associated with higher fiber intake in children raised on these diets. As older reports indicate that diets providing high fiber intake in children 0–5 years may affect growth, iron status and bowel function, we summarized the available evidence in this systematic review.

Objective: To identify, critically appraise, and synthesize evidence on the effect of high fiber intake on growth, iron and bowel function in children 0–5 years, with relevance to the Nordic and Baltic countries.

Methods: Following a pre-registered protocol, we searched MEDLINE, EMBASE, Cochrane Central of Controlled Trials, and Scopus for clinical trials and prospective cohort studies published until November 2021. Two reviewers independently screened retrieved literature, extracted relevant data, and performed risk of bias assessment. Outcomes were growth, iron metabolism and bowel function in children 0–5 years. We narratively described findings from studies that met inclusion criteria.

Results: From 5,644 identified records, five articles met the inclusion criteria. Two RCTs had an overall moderate risk of bias, while the three observational studies had serious risk. Overall, we found no robust association between high intake of dietary fiber and growth. In the RCTs, higher intake of fiber had a positive effect on bowel movements and constipation. No studies on fiber intake and iron status were identified.

The certainty of the overall evidence was inconclusive for growth and bowel function, while no assessment was made for iron status.

Conclusion: We found no clear association between high intake of dietary fiber and growth or bowel function in young children living in affluent countries, albeit with only a limited number of studies. There is a lack of studies investigating health effects of high fiber intake in small children.

Nuts and seeds consumption and risk of cardiovascular disease, type 2 diabetes and their risk factors: a systematic review and meta-analysis

Tue, 14 Feb 2023 00:00:00 -0800

Objectives: We aimed to systematically review studies and evaluate the strength of the evidence on nuts/seeds consumption and cardiometabolic diseases and their risk factors among adults.

Methods: A protocol was pre-registered in PROSPERO (CRD42021270554). We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to September 20, 2021 for prospective cohort studies and ≥12-week randomized controlled trials (RCTs). Main outcomes were cardiovascular disease (CVD), coronary heart disease (CHD), stroke and type 2 diabetes (T2D), secondary total-/low density lipoprotein (LDL)-cholesterol, blood pressure and glycaemic markers. Data extraction and risk of bias (RoB) assessments (using RoB 2.0 and RoB-NObS) were performed in duplicate. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk (RR) or weighted mean differences with 95% confidence intervals (CI); heterogeneity quantified as I². One-stage dose-response analyses assessed the linear and non-linear associations with CVD, CHD, stroke and T2D. The strength of evidence was classified per the World Cancer Research Fund criteria.

Results: After screening 23,244 references, we included 42 papers from cohort studies (28 unique cohorts, 1,890,573 participants) and 18 RCTs (2,266 participants). In the cohorts, mainly populations with low consumption, high versus low total nuts/seeds consumption was inversely associated with total CVD (RR 0.81; 95% CI 0.75, 0.86; I² = 67%), CVD mortality (0.77; 0.72, 0.82; I² = 59.3%), CHD (0.82; 0.76, 0.89; I² = 64%), CHD mortality (0.75; 0.65, 0.87; I² = 66.9%) and non-fatal CHD (0.85; 0.75, 0.96; I² = 62.2%). According to the non-linear dose-response analyses, consumption of 30 g/day of total nuts/seeds was associated with RRs of similar magnitude. For stroke and T2D the summary RR for high versus low intake was 0.91 (95% CI 0.85, 0.97; I² = 24.8%) and 0.95 (0.75, 1.21; I² = 82.2%). Intake of nuts (median ~50 g/day) lowered total (−0.15 mmol/L; −0.22, −0.08; I² = 31.2%) and LDL-cholesterol (−0.13 mmol/L; −0.21, −0.05; I² = 68.6%), but not blood pressure. Findings on fasting glucose, HbA1c and insulin resistance were conflicting. The results were robust to sensitivity and subgroup analyses. We rated the associations between nuts/seeds and both CVD and CHD as probable. There was limited but suggestive evidence for no association with stroke. No conclusion could be made for T2D.

Conclusion: There is a probable relationship between consumption of nuts/seeds and lower risk of CVD, mostly driven by CHD, possibly in part through effects on blood lipids. More research on stroke and T2D may affect the conclusions. The evidence of specific nuts should be further investigated.