Exploring the practicality and acceptability a brief exercise communication and clinician referral pathway in cancer care: a feasibility study.

BACKGROUND: The majority of cancer patients and cancer care clinicians-CCCs (e.g., oncologists) believe that exercise is an important adjunct therapy that should be embedded in standard practice. Yet, CCCs do not routinely discuss exercise with their patients, nor do they regularly refer them to exercise professionals (e.g., exercise physiologists-EPs). This study evaluated the feasibility and acceptability of an evidence-based approach to improving exercise communication between CCCs and their patients, including an exercise referral pathway. METHODS: Implementation and testing of the Exercise Communication and Referral Pathway (ECRP) occurred in Sydney, Australia. The ECRP included a brief oncology-initiated communication exchange with patients, CCC exercise referral to an EP, followed by EP-initiated telephone consultation with patients concerning tailored exercise advice. Participant perceptions concerning the feasibility and applicability of the ECPR were evaluated. Semi-structured interviews were conducted with CCCs (n = 3), cancer patients (n = 21), and an EP (n = 1). Inductive thematic analysis was undertaken. RESULTS: Analysis generated three themes: (1) Navigating the role of CCCs in the ECRP, suggesting that oncology-initiated communication is a cue to action, however there was a lack of role clarity regarding exercise referral; (2) Implementing Patient-Orientated Care within a Standardised Pathway, highlighting the need for tailored information and advice for patients that reflects individual disease, socio-cultural, and environmental factors, and; (3) Taking Steps Towards Action, revealing the need for structural (e.g., EP initiated contact with patients) and policy changes (i.e., changes to Medicare, direct oncologist referral) to engage patients and better integrate exercise as part of standard care. CONCLUSIONS: Findings provide important insights into improving oncology-patient exercise communication and developing an exercise referral pathway to increase engagement and patient reach. However, individual (e.g., experience, knowledge) and contextual factors (e.g., time, resources) need consideration when implementing an ECRP. TRIAL REGISTRATION: This trial was prospectively registered with the Australian New Zealand Clinical (#ACTRN12620000358943) on March 13, 2020.

Cytotoxicity of Fenugreek Sprout and Seed Extracts and Their Bioactive Constituents on MCF-7 Breast Cancer Cells.

Trigonella foenum-graecum L. (fenugreek), a member of the legume family (Fabaceae), is a promising source of bioactive phytochemicals, which explains its traditional use for a variety of metabolic disorders including cancer. The current study aimed to evaluate extracts of fenugreek seeds and sprouts, and some of their constituents, to compare their cytotoxic and antiproliferative activities in MCF-7 breast cancer cells. The extracts were chemically characterised using high-resolution accurate mass liquid chromatography-mass spectrometry to reveal the detection of compounds assigned as flavone C-glycosides including those derived from apigenin and luteolin, in addition to isoflavones. Five different flavones or their glycosides (apigenin, vicenin-2, vitexin, luteolin and orientin) and two isoflavones (daidzein and formononetin) were quantified in the fenugreek extracts. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using MCF-7 cells treated with fenugreek methanolic extracts showed dose- and time-dependent effects on cell viability. The MCF-7 cancer cells treated with the fenugreek methanolic extracts also displayed increased relative mitochondrial DNA damage as well as suppressed metastasis and proliferation. This study demonstrates the potential anti-cancer effects of fenugreek seeds and sprouts and reveals fenugreek sprouts as an untapped resource for bioactive compounds.

Iron.

Iron deficiency anemia affects approximately one-third of the world's population, and about half the cases are due to iron deficiency. The latest research on iron metabolism published in original articles and systematic reviews is described, and references to recent reviews provided. The topics include dietary sources and bioavailability, iron homeostasis, functions of iron in the body, and biomarkers of status. The consequences of iron deficiency and excess are discussed, with particular focus on vulnerable populations such as pregnant women, infants and the elderly. The newest dietary recommendations, including dietary reference values and food based dietary guidelines, are briefly summarized, followed by the latest developments in food fortification and iron supplementation.

In vitro bioaccessibility and bioavailability of iron from fenugreek, baobab and moringa.

Iron deficiency anaemia (IDA) is a common nutritional disorder worldwide. Sustainable food-based approaches are being advocated to use high and bioavailable dietary iron sources to prevent iron deficiency. The study investigated the bioaccessibility and bioavailability of iron from some plant products. Total iron levels in the samples were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Fractionation of the iron from the digested extracts was carried out by centrifugation and ultrafiltration. Iron bioavailability was determined using an in vitro simulated peptic-pancreatic digestion, followed by measurement of ferritin in Caco-2 cells. The highest amount of bioaccessible iron was obtained from moringa leaves (9.88% ± 0.45 and 8.44 ± 0.01 mg/100 g), but the highest percentage bioavailability was from baobab fruit pulp (99.7% ± 0.13 and 1.74 ± 0.01 mg/100 g) respectively. All the plant products, except for baobab, significantly inhibited iron uptake from FeSO4 and FAC, with fenugreek sprout being the most inhibitory.

Inhibition of the facilitative sugar transporters (GLUTs) by tea extracts and catechins.

Tea polyphenolics have been suggested to possess blood glucose lowering properties by inhibiting sugar transporters in the small intestine and improving insulin sensitivity. In this report, we studied the effects of teas and tea catechins on the small intestinal sugar transporters, SGLT1 and GLUTs (GLUT1, 2 and 5). Green tea extract (GT), oolong tea extract (OT), and black tea extract (BT) inhibited glucose uptake into the intestinal Caco-2 cells with GT being the most potent inhibitor (IC50 : 0.077 mg/mL), followed by OT (IC50 : 0.136 mg/mL) and BT (IC50 : 0.56 mg/mL). GT and OT inhibition of glucose uptake was partial non-competitive, with an inhibitor constant (Ki ) = 0.0317 and 0.0571 mg/mL, respectively, whereas BT was pure non-competitive, Ki  = 0.36 mg/mL. Oocytes injected to express small intestinal GLUTs were inhibited by teas, but SGLT1 was not. Furthermore, catechins present in teas were the predominant inhibitor of glucose uptake into Caco-2 cells, and gallated catechins the most potent: CG > ECG > EGCG ≥ GCG when compared to the non-gallated catechins (C, EC, GC, and EGC). In Caco-2 cells, individual tea catechins reduced the SGLT1 gene, but not protein expression levels. In contrast, GLUT2 gene and protein expression levels were reduced after 2 hours exposure to catechins but increased after 24 hours. These in vitro studies suggest teas containing catechins may be useful dietary supplements capable of blunting postprandial glycaemia in humans, including those with or at risk to Type 2 diabetes mellitus.

Iron and Zinc Homeostasis and Interactions: Does Enteric Zinc Excretion Cross-Talk with Intestinal Iron Absorption?

Iron and zinc are essential micronutrients required for growth and health. Deficiencies of these nutrients are highly prevalent among populations, but can be alleviated by supplementation and food fortification. Cross-sectional studies in humans showed positive association of serum zinc levels with hemoglobin and markers of iron status. Dietary restriction of zinc or intestinal specific conditional knock out of ZIP4 (SLC39A4), an intestinal zinc transporter, in experimental animals demonstrated iron deficiency anemia and tissue iron accumulation. Similarly, increased iron accumulation has been observed in cultured cells exposed to zinc deficient media. These results together suggest a potential role of zinc in modulating intestinal iron absorption and mobilization from tissues. Studies in intestinal cell culture models demonstrate that zinc induces iron uptake and transcellular transport via induction of divalent metal iron transporter-1 (DMT1) and ferroportin (FPN1) expression, respectively. It is interesting to note that intestinal cells are exposed to very high levels of zinc through pancreatic secretions, which is a major route of zinc excretion from the body. Therefore, zinc appears to be modulating the iron metabolism possibly via regulating the DMT1 and FPN1 levels. Herein we critically reviewed the available evidence to hypothesize novel mechanism of Zinc-DMT1/FPN1 axis in regulating intestinal iron absorption and tissue iron accumulation to facilitate future research aimed at understanding the yet elusive mechanisms of iron and zinc interactions.

Pea Ferritin Stability under Gastric pH Conditions Determines the Mechanism of Iron Uptake in Caco-2 Cells.

Background: Iron deficiency is an enduring global health problem that requires new remedial approaches. Iron absorption from soybean-derived ferritin, an ∼550-kDa iron storage protein, is comparable to bioavailable ferrous sulfate (FeSO4). However, the absorption of ferritin is reported to involve an endocytic mechanism, independent of divalent metal ion transporter 1 (DMT-1), the transporter for nonheme iron. Objective: Our overall aim was to examine the potential of purified ferritin from peas (Pisum sativum) as a food supplement by measuring its stability under gastric pH treatment and the mechanisms of iron uptake into Caco-2 cells. Methods: Caco-2 cells were treated with native or gastric pH-treated pea ferritin in combination with dietary modulators of nonheme iron uptake, small interfering RNA targeting DMT-1, or chemical inhibitors of endocytosis. Cellular ferritin formation, a surrogate measure of iron uptake, and internalization of pea ferritin with the use of specific antibodies were measured. The production of reactive oxygen species (ROS) in response to equimolar concentrations of native pea ferritin and FeSO4 was also compared. Results: Pea ferritin exposed to gastric pH treatment was degraded, and the released iron was transported into Caco-2 cells by DMT-1. Inhibitors of DMT-1 and nonheme iron absorption reduced iron uptake by 26-40%. Conversely, in the absence of gastric pH treatment, the iron uptake of native pea ferritin was unaffected by inhibitors of nonheme iron absorption, and the protein was observed to be internalized in Caco-2 cells. Chlorpromazine (clathrin-mediated endocytosis inhibitor) reduced the native pea ferritin content within cells by ∼30%, which confirmed that the native pea ferritin was transported into cells via a clathrin-mediated endocytic pathway. In addition, 60% less ROS production resulted from native pea ferritin in comparison to FeSO4. Conclusion: With consideration that nonheme dietary inhibitors display no effect on iron uptake and the low oxidative potential relative to FeSO4, intact pea ferritin appears to be a promising iron supplement.

Mindfulness training induces structural connectome changes in insula networks.

Although mindfulness meditation is known to provide a wealth of psychological benefits, the neural mechanisms involved in these effects remain to be well characterized. A central question is whether the observed benefits of mindfulness training derive from specific changes in the structural brain connectome that do not result from alternative forms of experimental intervention. Measures of whole-brain and node-level structural connectome changes induced by mindfulness training were compared with those induced by cognitive and physical fitness training within a large, multi-group intervention protocol (n = 86). Whole-brain analyses examined global graph-theoretical changes in structural network topology. A hypothesis-driven approach was taken to investigate connectivity changes within the insula, which was predicted here to mediate interoceptive awareness skills that have been shown to improve through mindfulness training. No global changes were observed in whole-brain network topology. However, node-level results confirmed a priori hypotheses, demonstrating significant increases in mean connection strength in right insula across all of its connections. Present findings suggest that mindfulness strengthens interoception, operationalized here as the mean insula connection strength within the overall connectome. This finding further elucidates the neural mechanisms of mindfulness meditation and motivates new perspectives about the unique benefits of mindfulness training compared to contemporary cognitive and physical fitness interventions.

In vitro assessment of iron availability from commercial Young Child Formulae supplemented with prebiotics.

PURPOSE: Iron is essential for development and growth in young children; unfortunately, iron deficiency (ID) is a significant public health problem in this population. Young Child Formulae (YCF), milk-derived products fortified with iron and ascorbic acid (AA, an enhancer of iron absorption) may be good sources of iron to help prevent ID. Furthermore, some YCF are supplemented with prebiotics, non-digestible carbohydrates suggested to enhance iron bioavailability. The aim of our study was to evaluate iron bioavailability of YCF relative to prebiotic and AA concentrations. We hypothesised that YCF with the highest levels of prebiotics and AA would have the most bioavailable iron. METHODS: We used the in vitro digestion/Caco-2 cell model to measure iron bioavailability from 4 commercially available YCF with approximately equal amounts of iron, but varying amounts of: AA and the prebiotics fructo- and galacto-oligosaccharides. Caco-2 cell ferritin formation was used as a surrogate marker for iron bioavailability. RESULTS: The YCF with the highest concentration of prebiotics and AA had the highest iron bioavailability; conversely, the YCF with the lowest concentration of prebiotics and AA had the lowest. After the addition of exogenous prebiotics, so that all tested YCF had equivalent amounts, there was no longer a significant difference between YCF iron bioavailability. CONCLUSION: Our results suggest that ascorbic acid and prebiotics in YCF improve iron bioavailability. Ensuring that iron is delivered in a bioavailable form would improve the nutritional benefits of YCF in relation to ID/IDA amongst young children; therefore, further exploration of our findings in vivo is warranted.

Iron bioavailability from commercially available iron supplements.

PURPOSE: Iron deficiency anaemia (IDA) is a global public health problem. Treatment with the standard of care ferrous iron salts may be poorly tolerated, leading to non-compliance and ineffective correction of IDA. Employing supplements with higher bioavailability might permit lower doses of iron to be used with fewer side effects, thus improving treatment efficacy. Here, we compared the iron bioavailability of ferrous sulphate tablets with alternative commercial iron products, including three liquid-based supplements. METHODS: Iron bioavailability was measured using Caco-2 cells with ferritin formation as a surrogate marker for iron uptake. Statistical analysis was performed using one-way ANOVA followed by either Dunnett's or Tukey's multiple comparisons tests. RESULTS: Spatone Apple(®) (a naturally iron-rich mineral water with added ascorbate) and Iron Vital F(®) (a synthetic liquid iron supplement) had the highest iron bioavailability. There was no statistical difference between iron uptake from ferrous sulphate tablets, Spatone(®) (naturally iron-rich mineral water alone) and Pregnacare Original(®) (a multimineral/multivitamin tablet). CONCLUSION: In our in vitro model, naturally iron-rich mineral waters and synthetic liquid iron formulations have equivalent or better bioavailability compared with ferrous iron sulphate tablets. If these results are confirmed in vivo, this would mean that at-risk groups of IDA could be offered a greater choice of more bioavailable and potentially better tolerated iron preparations.

Regulation of glucose transporter expression in human intestinal Caco-2 cells following exposure to an anthocyanin-rich berry extract.

Polyphenols contained within plant tissues are consumed in significant amounts in the human diet and are known to influence a number of biological processes. This study investigated the effects of an anthocyanin-rich berry-extract on glucose uptake by human intestinal Caco-2 cells. Acute exposure (15 min) to berry extract (0.125%, w/v) significantly decreased both sodium-dependent (Total uptake) and sodium-independent (facilitated uptake) ³H-D-glucose uptake. In longer-term studies, SGLT1 mRNA and GLUT2 mRNA expression were reduced significantly. Polyphenols are known to interact directly with glucose transporters to regulate the rate of glucose absorption. Our in vitro data support this mechanism and also suggest that berry flavonoids may modulate post-prandial glycaemia by decreasing glucose transporter expression. Further studies are warranted to investigate the longer term effects of berry flavonoids on the management of glycaemia in human volunteers.

The molecular basis of copper and iron interactions.

The intimate relationship between Fe and Cu in human nutrition has been recognised for many years. The best-characterised link is provided by caeruloplasmin, a multiCu-binding protein that acts as a serum ferrioxidase and is essential for the mobilisation of Fe from storage tissues. Decreased Cu status has been shown to reduce holo-caeruloplasmin production and impair ferrioxidase activity, leading, in a number of cases, to decreased tissue Fe release and the generation of anaemia that is responsive to dietary supplementation with Cu but not Fe. Dietary Fe absorption also requires the presence of a multiCu ferrioxidase. Hephaestin, a caeruloplasmin homologue, works in concert with the IREG1 transporter to permit Fe efflux from enterocytes for loading onto transferrin. The essential role of hephaestin in this process has been recognised from studies in the sex-linked anaemic (sla) mouse, in which Fe efflux is markedly impaired as a result of a mutation in the hephaestin gene that results in a truncated and non-functional version of the protein. There is emerging evidence that a number of other components of the intestinal Fe transport pathway are also Cu sensitive. Divalent metal transporter 1 (DMT1), the Fe transporter located at the apical membrane of enterocytes, is also a physiologically-relevant Cu transporter, suggesting that these two metals may compete with each other for uptake into the duodenal enterocytes. Furthermore, expression of both DMT1 and the basolateral Fe-efflux transporter IREG1 can be regulated by Cu, suggesting that the Fe-Cu relationship may be more complex than first thought.

Decreased expression of the vitamin C transporter SVCT1 by ascorbic acid in a human intestinal epithelial cell line.

Vitamin C (ascorbic acid) is an essential nutrient that is involved in a number of cellular processes. However, unlike most mammals, man is unable to synthesize vitamin C and it must therefore be acquired from the diet. Absorption of vitamin C is achieved by two transporters, SVCTI and SVCT2, recently cloned from rat and human kidney. SVCT1 is thought to be the predominant transporter in the intestine. Vitamin C supplements are increasingly common, thus contributing to an increased dietary load, and therefore the aim of the present study was to investigate the effect of high doses of ascorbic acid on SVCT1 expression. Using the Caco-2 TC7 cell model of small intestinal enterocytes, we measured the effects of ascorbic acid (4.5 mg/ml culture medium) on L-[14C]ascorbic acid uptake and SVCT1 expression (determined by reverse transcription-polymerase chain reaction). Ascorbic acid uptake was decreased significantly in Caco-2 TC7 cells exposed to ascorbate for 24 h (-50%, P<0.0005). Expression of SVCT1 was also significantly reduced by exposure to elevated levels of ascorbate for 24h (-77%, P<0.005). Taken together these results suggest that high-dose supplements might not be the most efficient way of increasing the body pool of vitamin C.