Synergic Role of Dietary Bioactive Compounds in Breast Cancer Chemoprevention and Combination Therapies.

Breast cancer is the most common tumor in women. Chemotherapy is the gold standard for cancer treatment; however, severe side effects and tumor resistance are the major obstacles to chemotherapy success. Numerous dietary components and phytochemicals have been found to inhibit the molecular and signaling pathways associated with different stages of breast cancer development. In particular, this review is focused on the antitumor effects of PUFAs, dietary enzymes, and glucosinolates against breast cancer. The major databases were consulted to search in vitro and preclinical studies; only those with solid scientific evidence and reporting protective effects on breast cancer treatment were included. A consistent number of studies highlighted that dietary components and phytochemicals can have remarkable therapeutic effects as single agents or in combination with other anticancer agents, administered at different concentrations and via different routes of administration. These provide a natural strategy for chemoprevention, reduce the risk of breast cancer recurrence, impair cell proliferation and viability, and induce apoptosis. Some of these bioactive compounds of dietary origin, however, show poor solubility and low bioavailability; hence, encapsulation in nanoformulations are promising tools able to increase clinical efficiency.

Sinigrin in combination with artesunate provides protection against lethal murine malaria via falcipain-3 inhibition and immune modulation.

Plant-derived antimalarials are indispensable for malaria treatment and a platform for new drugs. The present study explores sinigrin, for malaria using in vitro, in silico and in vivo strategies and the immune response generated after administration. The compound exhibited promising activity against chloroquine (CQ)-resistant (RKL-9) IC50 5.14 µg/mL and CQ-sensitive (3D7) IC50 5.47 µg/mL strains of P. falciparum and was safe in both in vitro (CC50 > 640 µg/mL) and in vivo (LD50 > 2 g/kg) toxicity studies. In addition, virtual screening showed hydrogen bonding, hydrophobic and van der Waals interactions with amino acid residues of 3BPM (falcipain-3). In vivo studies revealed promising antimalarial activity of sinigrin (200 mg/kg) with 87.44% chemo-suppression on day 5 and significantly (p < 0.0001) enhanced the mean survival time (21 ± 4.74 days) in contrast to the infected control (5.4 ± 1.14 days). In combination therapy, sinigrin (100 mg/kg and 200 mg/kg) augmented the efficacy of artesunate (AS 50 mg/kg) with 100% survival and no recrudescence. These observations are further corresponded and supported by DLC, NO production, cytokine analysis, biochemical and histopathological studies. Treatment with the combination resulted in a regulated interplay of immune cells and cytokines aiding in parasite clearance in addition to its specific inhibitory activity. We report the antimalarial activity of sinigrin first time with best D-score against falcipain-3. These findings highlight sinigrin as a HIT molecule, which may potentially be used in drug and vaccine development approaches.

Safety and tolerability of a natural supplement containing glucosinolates, phytosterols and citrus flavonoids in adult women: a randomized phase I, placebo-controlled, multi-arm, double-blinded clinical trial.

OBJECTIVE: To evaluate the safety and tolerability of an oral herbal supplement containing glucosinolates, phytosterols, and citrus flavonoids (Warmi®, Lima Perú;) in otherwise healthy adult women. METHODS: This was a phase-I, randomized parallel three arms, double-blinded, and a placebo-controlled clinical trial. A total of 55 participants aged 18-40 were randomly assigned to one of three groups to receive for three months: (1) an oral herbal supplement of 1650 mg/day; (2) an oral herbal supplement of 3300 mg/day; or (3) an oral placebo 3300 mg/day. The primary endpoints were oral safety and tolerability of the supplement. The secondary endpoint was its effect on vital functions, anthropometrics, and laboratory tests. We used an exploratory approach by covariance analysis (ANCOVA) adjusted for the variables' baseline value for the secondary outcomes. RESULTS: All women completed three months of follow-up, reporting no side effects. Our exploratory analysis revealed that treatment with the herbal supplement of 1650 mg/day was associated with increased glucose and uric acid levels. In comparison, the herbal supplement 3300 mg/day was associated with reduced breathing rate, increased basal temperature, and systolic blood pressure, both compared to the placebo group. However, despite significant differences, none of these was clinically significant. CONCLUSION: The oral herbal supplement had a favorable safety and tolerability profile in studied women. There is a need to study its potential as an option to treat menopausal symptoms.

Effects of different levels of rapeseed cake containing high glucosinolates in steer ration on rumen fermentation, nutrient digestibility and the rumen microbial community.

This trial was conducted to study the effects of dietary rapeseed cake (RSC) containing high glucosinolates (GLS) on rumen fermentation, nutrient digestion and the rumen microbial community in steers. Eight growing steers and four rations containing RSC (GLS 226·1 µmol/g DM) at 0·00, 2·65, 5·35 and 8·00 % DM were assigned in a replicate 4 × 4 Latin square design. The results indicated that increasing RSC levels increased the ruminal concentration of thiocyanate (SCN) (P < 0·01), decreased the ruminal concentration of ammonia nitrogen (NH3-N) and the molar proportion of isovalerate (P < 0·05), did not affect the ruminal concentration of total volatile fatty acids (P > 0·05), decreased the crude protein (CP) digestibility (P < 0·05) and increased the ether extract (EE) digestibility (P < 0·01). Increasing RSC levels tended to decrease the abundances of ruminal Ruminobacter amylophilus (P = 0·055) and Ruminococcus albus (P = 0·086) but did not affect methanogens, protozoa, fungi and other bacteria (P > 0·05). Increasing RSC levels in the ration did not affect the ruminal bacterial diversity (P > 0·05), but it increased the operational taxonomic units and the bacterial richness (P < 0·05) and affected the relative abundances of some bacteria at the phylum level and genus level (P < 0·05). In conclusion, RSC decreased the ruminal concentration of NH3-N and the CP digestibility, increased the EE digestibility and partly affected the ruminal bacterial community. SCN, as the metabolite of GLS, could be a major factor affecting these indices.

The mother relationship between insulin resistance and non-alcoholic steatohepatitis: Glucosinolates hydrolysis products as a promising insulin resistance-modulator and fatty liver-preventer.

Non-alcoholic fatty liver disease (NFLD) is one of the present public health problems which have no specific and effective treatment. The speed of the disease progression depends on the patient's lifestyle. Due to life stresses and lack of time, a high number of people depend on fast food containing a high amount of fats which one of the main causes of insulin resistance (IR). IR is one of the metabolic disorders which strongly intersected with molecular NAFLD and leading to its progression into non-alcoholic steatohepatitis (NASH). In this review, we introduced the updated statistics of NAFLD and NASH progression all over the world shows its importance, etiologies, and pathogenesis. Also, IR and its role in NASH initiation and progression explored, and current treatments with its limitations have been explained. Glucosinolates (GLS) is a group of phytochemicals which known by its potent hydrolysis products with promising anti-cancer effect. In this review, we have collected the recent experimental studies of different GLS hydrolysis products against IR and chronic liver diseases supported by our lab finding. Finally, we recommend this group of phytochemicals as promising molecules to be studied experimentally and clinically against a wide range of chronic liver diseases with an acceptable safety margin.

Dietary intake of glucoraphanin during pregnancy and lactation prevents the behavioral abnormalities in the offspring after maternal immune activation.

AIM: Epidemiological data suggest that maternal immune activation (MIA) plays a role in the etiology of neuropsychiatric disorders including autism spectrum disorder (ASD) and schizophrenia. However, there is no prophylactic nutrition that can prevent the onset of neurodevelopmental disorders in offspring after MIA. The aim of this study was undertaken to examine whether dietary intake of glucoraphanin (GF: the precursor of a natural anti-inflammatory compound sulforaphane) can prevent the onset of behavioral abnormalities in offspring after MIA. METHODS: One percent of GF food pellet or normal food pellet was given into female mice during pregnancy and lactation (from E5 to P21). Saline (5 mL/kg/d) or poly(I:C) (5 mg/kg/d) was injected into pregnant mice from E12 to E17. Behavioral tests and immunohistochemistry of parvalbumin (PV) were performed in male offspring. RESULTS: Dietary intake of GF during pregnancy and lactation prevented cognitive deficits and social interaction deficits in the juvenile offspring after MIA. Furthermore, dietary intake of GF during pregnancy and lactation prevented cognitive deficits in the adult offspring after MIA. Moreover, dietary intake of GF prevented the reduction of PV immunoreactivity in the medial prefrontal cortex of adult offspring after MIA. CONCLUSION: These data suggest that dietary intake of GF during pregnancy and lactation could prevent behavioral abnormalities in offspring after MIA.

Targeting hallmarks of cancer with a food-system-based approach.

Although extensive resources are dedicated to the development and study of cancer drugs, the cancer burden is expected to rise by about 70% over the next 2 decade. This highlights a critical need to develop effective, evidence-based strategies for countering the global rise in cancer incidence. Except in high-risk populations, cancer drugs are not generally suitable for use in cancer prevention owing to potential side effects and substantial monetary costs (Sporn, 2011). There is overwhelming epidemiological and experimental evidence that the dietary bioactive compounds found in whole plant-based foods have significant anticancer and chemopreventative properties. These bioactive compounds often exert pleiotropic effects and act synergistically to simultaneously target multiple pathways of cancer. Common bioactive compounds in fruits and vegetables include carotenoids, glucosinolates, and polyphenols. These compounds have been shown to target multiple hallmarks of cancer in vitro and in vivo and potentially to address the diversity and heterogeneity of certain cancers. Although many studies have been conducted over the past 30 y, the scientific community has still not reached a consensus on exactly how the benefit of bioactive compounds in fruits and vegetables can be best harnessed to help reduce the risk for cancer. Different stages of the food processing system, from "farm-to-fork," can affect the retention of bioactive compounds and thus the chemopreventative properties of whole foods, and there are opportunities to improve handling of foods throughout the stages in order to best retain their chemopreventative properties. Potential target stages include, but are not limited to, pre- and postharvest management, storage, processing, and consumer practices. Therefore, there is a need for a comprehensive food-system-based approach that not only taking into account the effects of the food system on anticancer activity of whole foods, but also exploring solutions for consumers, policymakers, processors, and producers. Improved knowledge about this area of the food system can help us adjust farm-to-fork operations in order to consistently and predictably deliver desired bioactive compounds, thus better utilizing them as invaluable chemopreventative tools in the fight to reduce the growing burden of cancer worldwide.

A Strategy to Deliver Precise Oral Doses of the Glucosinolates or Isothiocyanates from Moringa oleifera Leaves for Use in Clinical Studies.

The tropical tree Moringa oleifera produces high yields of protein-rich leaf biomass, is widely used as a food source, contains an abundance of phytochemicals, and thus has great potential for chronic disease prevention and perhaps, treatment. We have developed and characterized standardized ways of preparing aqueous "teas" from moringa leaves to deliver precisely calibrated levels of phytochemicals for use in clinical trials. These phytochemicals, especially the glucosinolate glucomoringin and the isothiocyanate moringin, produced from it following hydrolysis by the enzyme myrosinase, provide potent anti-inflammatory and cytoprotective indirect antioxidant activity. The taste of both hot and cold teas is palatable without the need for flavor masking. These teas can be easily and reproducibly prepared in underserved tropical regions of the world where moringa is cultivated. Isothiocyanate yield from a cold extraction was rapid and essentially complete after 30 min and its anti-inflammatory potential is comparable to that of equimolar purified moringin. A preparation similar to this may be safe to consume with respect to its bacterial titer even after 48 h without refrigeration. Thus, facile delivery of moringa tea to both adults and children for clinical evaluation of their effects on such conditions as autism, diabetes, and hypertension, is now possible.

Bioavailability of Sulforaphane Following Ingestion of Glucoraphanin-Rich Broccoli Sprout and Seed Extracts with Active Myrosinase: A Pilot Study of the Effects of Proton Pump Inhibitor Administration.

We examined whether gastric acidity would affect the activity of myrosinase, co-delivered with glucoraphanin (GR), to convert GR to sulforaphane (SF). A broccoli seed and sprout extract (BSE) rich in GR and active myrosinase was delivered before and after participants began taking the anti-acid omeprazole, a potent proton pump inhibitor. Gastric acidity appears to attenuate GR bioavailability, as evidenced by more SF and its metabolites being excreted after participants started taking omeprazole. Enteric coating enhanced conversion of GR to SF, perhaps by sparing myrosinase from the acidity of the stomach. There were negligible effects of age, sex, ethnicity, BMI, vegetable consumption, and bowel movement frequency and quality. Greater body mass correlated with reduced conversion efficiency. Changes in the expression of 20 genes in peripheral blood mononuclear cells were evaluated as possible pharmacodynamic indicators. When grouped by their primary functions based on a priori knowledge, expression of genes associated with inflammation decreased non-significantly, and those genes associated with cytoprotection, detoxification and antioxidant functions increased significantly with bioavailability. Using principal components analysis, component loadings of the changes in gene expression confirmed these groupings in a sensitivity analysis.

Chemical Analysis of Lepidium meyenii (Maca) and Its Effects on Redox Status and on Reproductive Biology in Stallions †.

The present study was conducted to assess the chemical composition of Yellow Maca (Lepidium meyenii) and its biological activity on stallions following oral administration of hypocotyl powder. Maca was subjected to methanolic extraction and the chemical analysis was carried out by LC-MS-QTOF (liquid chromatography-mass spectrometry). Our results showed that Maca contains some effective antioxidants, a high percentage of glucosinolates, and other important components with a high antioxidant capacity. To evaluate the plant biological activity in stallions fed with Maca powder for 60 days, the redox status and some reproductive parameters were investigated. Blood and semen samples were collected at 0, 30, 60, and 90 days from the beginning of this study. Blood samples showed a decrease of the reactive oxygen metabolites, evaluated by d-ROMs test, and an increase of the antioxidant barrier in terms of biological antioxidant potential (BAP test), powerful oxidant capacity (OXY-Adsorbent test), and thiols evaluation (-SHp test). Furthermore, semen samples showed a positive trend during Maca administration in the following parameters: ejaculate volumes and sperm concentrations, total and progressive motility, and acrosome integrity.

Dietary intake of glucoraphanin prevents the reduction of dopamine transporter in the mouse striatum after repeated administration of MPTP.

AIMS: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Although diet may influence the development of PD, the precise mechanisms underlying relationship between diet and PD pathology are unknown. Here, we examined whether dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane in cruciferous vegetables, can affect the reduction of dopamine transporter (DAT) in the mouse striatum after repeated administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). METHODS: Normal food pellet or 0.1% GF food pellet was given into male mice for 28 days from 8-week-old. Subsequently, saline (5 mL/kg × 3, 2-hour interval) or MPTP (10 mg/kg × 3, 2-hour interval) was injected into mice. Immunohistochemistry of DAT in the striatum was performed 7 days after MPTP injection. RESULTS: Repeated injections of MPTP significantly decreased the density of DAT-immunoreactivity in the mouse striatum. In contrast, dietary intake of 0.1% GF food pellet significantly protected against MPTP-induced reduction of DAT-immunoreactivity in the striatum. CONCLUSION: This study suggests that dietary intake of GF food pellet could prevent MPTP-induced dopaminergic neurotoxicity in the striatum of adult mice. Therefore, dietary intake of GF-rich cruciferous vegetables may have beneficial effects on prevention for development of PD.

Piglet performance and physiological effects linked to reduced glucosinolate transformations in feed products based on rapeseed pressed cakes.

The nutritional quality of rapeseed press cakes (RPCs) in piglet feed is closely linked to its digestibility and the content of glucosinolates. This study investigates the significance of intact glucosinolate (glc) levels and degree of glc transformations on piglets performance. Four different RPCs were made from a low glc (11 µmol/g seed DM) containing B. napus L. seed variety Lioness (RPC-LW, RPC-LXW, RPC-LC, RPC-LCD). RPC made from the variety Excalibur containing the upper level of glc (24 µmol/g seed DM) of double rapeseed and produced at higher and prolonged temperature (RPC-UXW) served as negative control, while soya bean protein concentrate served as positive control. Piglets (8 kg) were fed ad libitum diets balanced for RPC protein content, with RPC inclusion of 84-98 g/kg (day 0-14) and 151-178 g/kg (day 15-50). Glc transformation was reduced from 42% to 24% (7.3-4.2 µmol/g RPC) when the temperature input was lowered in the warm pressing of oil, while the glc loss was less pronounced (17%) when cold pressing was applied. The following feed pelleting process further reduced Glc concentration from 11% to 40% in warm-pressed RPCs and 54 to 85% in cold-pressed RPCs. The RPC products replaced soya bean protein without any negative effects on performance, except for piglets served cold-pressed RPC, which had a reduction in average daily weight gain (ADG) (5%-7%, p < 0.05, Day 15-50). RPC in the feed led to increased liver weight in all piglets (p = 0.026). This may point at long-term effects from feeding with RPC. Intestinal absorption of intact glcs was proven by their detection in urine. In conclusion, warm-pressed RPC can be used as feed for piglet, while the presence of active myrosinase may have a negative effect on performance and cakes should either be included in lower amounts than used in the present study (18%) or include myrosinase inactivation before use.

Interleukin-22 protects intestinal stem cells against genotoxic stress.

Environmental genotoxic factors pose a challenge to the genomic integrity of epithelial cells at barrier surfaces that separate host organisms from the environment. They can induce mutations that, if they occur in epithelial stem cells, contribute to malignant transformation and cancer development1-3. Genome integrity in epithelial stem cells is maintained by an evolutionarily conserved cellular response pathway, the DNA damage response (DDR). The DDR culminates in either transient cell-cycle arrest and DNA repair or elimination of damaged cells by apoptosis4,5. Here we show that the cytokine interleukin-22 (IL-22), produced by group 3 innate lymphoid cells (ILC3) and γδ T cells, is an important regulator of the DDR machinery in intestinal epithelial stem cells. Using a new mouse model that enables sporadic inactivation of the IL-22 receptor in colon epithelial stem cells, we demonstrate that IL-22 is required for effective initiation of the DDR following DNA damage. Stem cells deprived of IL-22 signals and exposed to carcinogens escaped DDR-controlled apoptosis, contained more mutations and were more likely to give rise to colon cancer. We identified metabolites of glucosinolates, a group of phytochemicals contained in cruciferous vegetables, to be a widespread source of genotoxic stress in intestinal epithelial cells. These metabolites are ligands of the aryl hydrocarbon receptor (AhR)6, and AhR-mediated signalling in ILC3 and γδ T cells controlled their production of IL-22. Mice fed with diets depleted of glucosinolates produced only very low levels of IL-22 and, consequently, the DDR in epithelial cells of mice on a glucosinolate-free diet was impaired. This work identifies a homeostatic network protecting stem cells against challenge to their genome integrity by AhR-mediated 'sensing' of genotoxic compounds from the diet. AhR signalling, in turn, ensures on-demand production of IL-22 by innate lymphocytes directly regulating components of the DDR in epithelial stem cells.

Supplementation of the Diet by Exogenous Myrosinase via Mustard Seeds to Increase the Bioavailability of Sulforaphane in Healthy Human Subjects after the Consumption of Cooked Broccoli.

SCOPE: Broccoli contains glucosinolate glucoraphanin, which, in the presence of myrosinase, can hydrolyze to isothiocyanate sulforaphane, reported to have anticarcinogenic activity. However, the myrosinase enzyme is denatured on cooking. Addition of an active source of myrosinase, such as from powdered mustard seed, to cooked Brassica vegetables can increase the release of health beneficial isothiocyanates; however, this has not previously been proven in vivo. METHODS AND RESULTS: The concentration of sulforaphane metabolite (sulforaphane N-acetyl-l-cysteine [SF-NAC]) in 12 healthy adults after the consumption of 200 g cooked broccoli, with and without 1 g powdered brown mustard, was studied in a randomized crossover design. During the 24-h period following the consumption of the study sample, all urine was collected. SF-NAC content was assayed by HPLC. When study subjects ingested cooked broccoli alone, mean urinary SF-NAC excreted was 9.8 ± 5.1 µmol per g creatinine, and when cooked broccoli was consumed with mustard powder, this increased significantly to 44.7 ± 33.9 µmol SF-NAC per gram creatinine. CONCLUSION: These results conclude that when powdered brown mustard is added to cooked broccoli, the bioavailability of sulforaphane is over four times greater than that from cooked broccoli ingested alone.

Dietary glucosinolates and risk of type 2 diabetes in 3 prospective cohort studies.

Background: Glucosinolates are a group of phytochemicals that are abundant in cruciferous vegetables and precursors of the potentially chemopreventive isothiocyanates. Isothiocyanates may reduce oxidative stress and inflammation, but little is known regarding the association between glucosinolate intake and risk of type 2 diabetes (T2D). Objective: To evaluate the association between the intake of glucosinolates and the incidence of T2D in US men and women. Design: This prospective cohort study investigated 200,907 women and men [71,256 women from the Nurses' Health Study (NHS; 1984-2012), 88,293 women from the NHS II (1991-2013), and 41,358 men from the Health Professionals Follow-Up Study (1986-2012)] who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed using validated semiquantitative food frequency questionnaires. Self-reported T2D incidence was confirmed by a supplementary questionnaire. Results: During follow-up in the 3 cohorts, we accumulated 4,303,750 person-years and 16,567 incident cases of T2D. After adjustment for major lifestyle and dietary risk factors for T2D, participants in the highest quintile of total glucosinolate intake had a 19% higher risk (95% CI: 13%, 25%; Ptrend < 0.001) of T2D than did those in the lowest quintile. The intake of 3 major glucosinolate subtypes was consistently and significantly associated with T2D risk, with pooled HRs ranging from 1.13 to 1.18 (all Ptrend < 0.001). A significant association was also observed between total cruciferous vegetable consumption and T2D (HR: 1.16; 95% CI :1.07, 1.25; Ptrend < 0.001). These associations persisted in subgroups defined by demographic, lifestyle, and other dietary factors. Conclusions: Dietary glucosinolate intake was associated with a moderately higher risk of T2D in US adults. These results need to be replicated in further investigations, including biomarker-based studies. Mechanistic research is also needed to understand the relation between exposures to glucosinolates, isothiocyanates, and other metabolites with T2D risk. This trial was registered at clinicaltrials.gov as NCT03366532.

Glucosinolate and isothiocyanate intakes are inversely associated with breast cancer risk: a case-control study in China.

Although previous studies have investigated the association of cruciferous vegetable consumption with breast cancer risk, few studies focused on the association between bioactive components in cruciferous vegetables, glucosinolates (GSL) and isothiocyanates (ITC), and breast cancer risk. This study aimed to examine the association between consumption of cruciferous vegetables and breast cancer risk according to GSL and ITC contents in a Chinese population. A total of 1485 cases and 1506 controls were recruited into this case-control study from June 2007 to March 2017. Consumption of cruciferous vegetables was assessed using a validated FFQ. Dietary GSL and ITC were computed by using two food composition databases linking GSL and ITC contents in cruciferous vegetables with responses to the FFQ. The OR and 95 % CI were assessed by unconditional logistic regression after adjusting for the potential confounders. Significant inverse associations were found between consumption of cruciferous vegetables, GSL and ITC and breast cancer risk. The adjusted OR comparing the highest with the lowest quartile were 0·51 (95 % CI 0·41, 0·63) for cruciferous vegetables, 0·54 (95 % CI 0·44, 0·67) for GSL and 0·62 (95 % CI 0·50, 0·76) for ITC, respectively. These inverse associations were also observed in both premenopausal and postmenopausal women. Subgroup analysis by hormone receptor status found inverse associations between cruciferous vegetables, GSL and ITC and both hormone-receptor-positive or hormone-receptor-negative breast cancer. This study indicated that consumption of cruciferous vegetables, GSL and ITC was inversely associated with breast cancer risk among Chinese women.

Bioavailability of Isothiocyanates From Broccoli Sprouts in Protein, Lipid, and Fiber Gels.

SCOPE: Optimization of bioavailability of dietary bioactive health-beneficial compounds is as important as increasing their concentration in foods. The aim of this study is to explore the change in bioavailability of isothiocyanates (ITCs) in broccoli sprouts incorporated in protein, fiber, and lipid gels. METHODS AND RESULTS: Five participants took part in a cross-over study and collected timed urine samples up to 24 h after consumption of proteins, dietary fibers, and lipid gels containing broccoli sprouts powder. Sulforaphane and iberin metabolites were determined in the urine samples. Samples in which sulforaphane and iberin were preformed by myrosinase led to a higher bioavailability of those compounds. Compared to the control broccoli sprout, incorporation of sprouts in gels led to lower bioavailability for preformed sulforaphane and iberin (although for sulforaphane the lower bioavailability was not significantly different) whereas for the gels rich in their precursors, glucoraphanin and glucoiberin, the opposite trend was observed (although not significantly different). CONCLUSION: This explorative study suggests that ITCs bioavailability can be modulated by food structure and composition and further and deeper investigations are needed to develop food products that lead to an optimized ITCs bioavailability.

Dietary glucoraphanin prevents the onset of psychosis in the adult offspring after maternal immune activation.

Maternal immune activation (MIA) contributes to behavioral abnormalities relevant to schizophrenia in adult offspring, although the molecular mechanisms underlying MIA-induced behavioral changes remain unclear. Here we demonstrated that dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane, during juvenile and adolescent stages prevented cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial prefrontal cortex (mPFC) of adult offspring after MIA. Gene set enrichment analysis by RNA sequencing showed that MIA caused abnormal expression of centrosome-related genes in the PFC and hippocampus of adult offspring, and that dietary intake of GF improved these abnormal gene expressions. Particularly, MIA increased the expression of suppressor of fermentation-induced loss of stress resistance protein 1 (Sfi1) mRNA in the PFC and hippocampus of adult offspring, and dietary intake of GF prevented the expression of Sfi1 mRNA in these regions. Interestingly, we found altered expression of SFI1 in the postmortem brains and SFI1 mRNA in hair follicle cells from patients with schizophrenia compared with controls. Overall, these data suggest that centrosome-related genes may play a role in the onset of psychosis in offspring after MIA. Therefore, dietary intake of GF-rich vegetables in high-risk psychosis subjects may prevent the transition to psychosis in young adulthood.

Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention.

Chemoprevention-the use of medication to prevent cancer-can be augmented by the consumption of produce enriched with natural metabolites. However, chemopreventive metabolites are typically inactive and have low bioavailability and poor host absorption. Here, we show that engineered commensal microbes can prevent carcinogenesis and promote the regression of colorectal cancer through a cruciferous vegetable diet. The engineered commensal Escherichia coli bound specifically to the heparan sulphate proteoglycan on colorectal cancer cells and secreted the enzyme myrosinase to transform host-ingested glucosinolates-natural components of cruciferous vegetables-to sulphoraphane, an organic small molecule with known anticancer activity. The engineered microbes coupled with glucosinolates resulted in >95% proliferation inhibition of murine, human and colorectal adenocarcinoma cell lines in vitro. We also show that murine models of colorectal carcinoma fed with the engineered microbes and the cruciferous vegetable diet displayed significant tumour regression and reduced tumour occurrence.