Dietary Porphyra tenera ameliorated dextran sodium sulfate-induced colitis in mice via modulating gut microbiota dysbiosis.

Bioactive components from Porphyra tenera (PT) have been reported to confer various health benefits. The role of PT in inflammatory bowel disease (IBD) has not been fully investigated. This study aimed to explore the anti-inflammatory properties of PT on dextran sodium sulfate (DSS)-treated mice. PT supplementation attenuated the severity of colitis in DSS-treated mice, evidenced by the reduction of disease activity index (DAI), restoration of colonic histological damage and suppression of abnormal inflammatory response. Sequencing analysis indicated that intake of PT alleviated DSS-induced gut microbiota dysbiosis, accompanied by reversing the generation of short-chain fatty acids (SCFAs) and bile acids (BAs). Overall, our findings demonstrated that supplementation of PT attenuated the severity of intestinal inflammation and ameliorated gut microbiota dysbiosis in a murine colitis model, which provided a rationale for further application of edible seaweeds for preventing inflammation-related disorders in humans.

Unveiling the role of gut microbiota in curcumin metabolism using antibiotic-treated mice.

Curcumin might exert its therapeutic effects by interacting with gut microbiota. However, the role of gut microbiota in curcumin metabolism in vivo remains poorly understood. To address this, we used antibiotics to deplete gut microbiota and compared curcumin metabolism in control and antibiotic-treated mice. Using Q-TOF and triple quadrupole mass spectrometry, we identified and quantified curcumin metabolites, revealing distinct metabolic pathways in these two mice groups. The novel metabolites, hexahydro-dimethyl-curcumin and hexahydro-didemethyl-curcumin were exclusively derived from gut microbiota. Additionally, gut bacteria deconjugated curcumin metabolites back into their bioactive forms. Moreover, control mice exhibited significantly lower curcumin degradation, suggesting a protective role of gut microbiota against degradation. In conclusion, our results indicated that gut microbiota might enhance the effectiveness of curcumin by deconjugation, production of active metabolites, and protection against degradation in the large intestine. This study enhances our understanding of the interactions between curcumin and gut microbiota.

Metabolomics study of dietary Pleurotus eryngii ß-type glycosidic polysaccharide on colitis induced by dextran sodium sulfate in mice - Exploration for the potential metabolic indicators in urine and serum.

Pleurotus eryngii, an edible mushroom recognized for its potent polysaccharides, demonstrates significant regulatory effects on metabolic processes. ß-glucan (WPEP) derived from P. eryngii has been noted for its therapeutic potential, exhibiting notable benefits in alleviating colonic inflammation and restructuring gut microbiota in mice treated with dextran sodium sulfate (DSS). This study focuses on utilizing DSS-induced colitis mice to explore the efficacy and underlying mechanisms of WPEP in ameliorating colitis, employing a metabolomics approach analyzing urine and serum. The findings reveal that WPEP administration effectively regulates metabolic imbalances in DSS mice, impacting purine metabolism, pentose and glucuronic acid interconversion, amino acid metabolism, primary bile acid biosynthesis, citric acid cycle, and lipid metabolism. Furthermore, WPEP demonstrates a capacity to modulate colitis by regulating diverse metabolic pathways, consequently influencing intestinal barrier integrity, motility, inflammation, oxidative stress, and immunity. These insights suggest that WPEP is a promising food component for managing inflammatory bowel diseases.

The Anti-inflammatory Potential of a Strain of Probiotic Bifidobacterium pseudocatenulatum G7: In Vitro and In Vivo Evidence.

The genus Bifidobacterium has been widely used in functional foods for health promotion due to its beneficial effects on human health, especially in the gastrointestinal tract (GIT). In this study, we characterize the anti-inflammatory potential of the probiotic strain Bifidobacterium pseudocatenulatum G7, isolated from a healthy male adult. G7 secretion inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Moreover, oral administration of bacteria G7 alleviated the severity of colonic inflammation in dextran sulfate sodium (DSS)-treated colitis mice, which was evidenced by a decreased disease activity index (DAI) and enhanced structural integrity of the colon. The 16S rRNA gene sequencing result illustrated that the G7 alleviated DSS-induced gut microbiota dysbiosis, accompanied by the modulated bile acids and short-chain fatty acid (SCFA) levels. Overall, our results demonstrated the potential anti-inflammatory effects of Bifidobacterium pseudocatenulatum G7 on both in vitro and in vivo models, which provided a solid foundation for further development of a novel anti-inflammatory probiotic.

Aptamer-aided plasmonic nano-urchins for reporter-free surface-enhanced Raman spectroscopy analysis of cortisol.

Cortisol is a vital glucocorticoid hormone reflecting stress levels and related disease processes. In this study, we report an aptamer-functionalized plasmonic nano-urchin (α-FeOOH@Au-aptamer)-aided cortisol-capturing and surface-enhanced Raman spectroscopy (SERS) analysis approach. The designed α-FeOOH@Au-aptamer exhibits a well-patterned plasma structure, which combines the good SERS enhancement ability of reduced nanogaps between the Au plasma and the hot spot-favored structure of anisotropic tips from α-FeOOH urchins, with the high affinity of the aptamer towards cortisol molecules. The α-FeOOH@Au-aptamer achieved reporter-free SERS quantification for cortisol with good sensitivity (limit of detection <0.28 µmol L-1), robust salt (1.0 mol per L NaCl) and protein (5.0 mg per mL bovine serum protein) tolerance, favorable reproducibility, as well as good reusability. We further demonstrated the good cortisol-capturing ability and SERS efficacy of the α-FeOOH@Au-aptamer profiling in the serum and urine samples. Our approach provides an alternative tool for cortisol analysis and a reference strategy for report-free SERS detection of small molecules.

Dietary intake of whole king oyster mushroom (Pleurotus eryngii) attenuated obesity via ameliorating lipid metabolism and alleviating gut microbiota dysbiosis.

There is a growing interest in employing whole food-based strategies to prevent chronic diseases, owing to the potential synergistic interactions among various bioactive components found within whole foods. The current research aimed to determine inhibitory effects of the whole edible mushroom Pleurotus eryngii (WPE) on high-fat diet (HFD)-induced obesity in mice. Our results showed that dietary intake of WPE significantly inhibited the abnormal gain of body weight and adipose tissue weight, improved glucose tolerance, and ameliorated the serum biochemical parameters in HFD-fed mice. The histological analysis illustrated that the severity of non-alcoholic fatty liver induced by HFD was significantly reduced by WPE. Oral intake of WPE profoundly modulated the mRNA levels of hepatic genes involved in lipid metabolism and also increased the level of short-chain fatty acids in the mouse cecum. Moreover, WPE alleviated the HFD-induced gut microbiota dysbiosis, increasing the abundance of beneficial bacteria (Akkermansia, Lactobacillus, Bifidobacterium, and Sutteralla), and decreasing the harmful ones (rc4-4, Dorea, Coprococcus, Oscillospira, and Ruminococcus). These findings presented new evidence supporting that WPE could be used as a whole food-based strategy to protect against obesity and obesity-driven health problems.

Expression of Toll-like receptors and host defence peptides in the cecum of chicken challenged with Eimeria tenella.

Chicken coccidiosis, caused by Eimeria protozoa, affects poultry farming. Toll-like receptors (TLRs) and host defence peptides (HDPs) help host innate immune responses to eliminate invading pathogens, but their roles in Eimeria tenella infection remain poorly understood. Herein, 14-day-old chickens were treated orally with 50,000 E. tenella oocysts and the cecum was dissected at different timepoints. mRNA expression of 10 chicken TLRs (chTLRs) and five HDPs was measured by quantitative real-time PCR. chTLR7 and chTLR15 were upregulated significantly at 3 h post-infection while other chTLRs were downregulated (p < .05). chTLR1a, chTLR1b, chTLR2b and chTLR4 peaked at 36 h post-infection, chTLR3, chTLR5 and chTLR15 peaked at 72 h post-infection and chTLR21 expression was highest among chTLRs, peaking at 48 h post-infection (p < 0.05). For HDPs, cathelicidin (CATH) 1 to 3 and B1 peaked at 48 h post-infection, liver-expressed antimicrobial peptide 2 peaked at 96 h post-infection, and CATH 2 expression was highest among HDPs. CATH2 and CATH3 were markedly upregulated at 3 h post-infection (p < .05). The results provide insight into innate immune molecules during E. tenella infection in chicken, and indicate that innate immune responses may mediate resistance to chicken coccidiosis.

N-Ethyl-N-Nitrosourea Induced Leukaemia in a Mouse Model: Protective Effect of Icaritin via Inhibition of IL-6/JAK2/STAT3 Pathway Causes Apoptosis.

Background: The present study aimed to investigate the protective effect of icaritin (ICT) on ENU-induced leukemia in male mice. Methods: The mice received intraperitoneal injections of 80 mg/kg ENU twice a week for three months for induction of leukemia. Blood smears from these mice showed blast cells, confirming the presence of leukemia. After confirming leukemia, mice were divided into control, ENU-induced leukemia, and leukemia groups (10 mg/kg bw and 20 mg/kg bw) were treated with ICT for 35 days. Blood, spleen, and liver samples were collected for analysis. The expression of IL-6, JAK2, STAT3, as well as inflammatory, pro-apoptotic (Bax), and anti-apoptotic (Bcl-2) proteins were evaluated using qPCR, immunohistochemistry, and immunofluorescence techniques. Results: The study found that ICT inhibited inflammation and the IL-6/JAK2/STAT3 pathway in ENU-induced mice. ICT treatment induced apoptosis in the spleen and liver by activating Bax and downregulating Bcl-2. The findings provide novel evidence that ICT acts as a dual inhibitor of IL-6/JAK2/STAT3 signaling, promoting apoptosis and playing an essential role in anti-leukemic activity. Conclusion: These results suggest that ICT has potential as a therapeutic target for treating leukemia, offering a novel approach to leukemia treatment through inhibiting the IL-6/JAK2/STAT3 pathway and induction of apoptosis.

Dietary nobiletin regulated cefuroxime- and levofloxacin-associated "gut microbiota-metabolism" imbalance and intestinal barrier dysfunction in mice.

Nobiletin (NOB) exhibits significant biological activities and may be a potential dietary treatment for antibiotic-associated gut dysbiosis. In this study, mice were gavaged with 0.2 mL day-1 of 12.5 g L-1 cefuroxime (LFX) and 10 g L-1 levofloxacin (LVX) for a duration of 10 days, accompanied by 0.05% NOB to investigate the regulatory effect and potential mechanisms of NOB on antibiotic-induced intestinal microbiota disorder and intestinal barrier dysfunction. Our results indicated that dietary NOB improved the pathology of intestinal epithelial cells and the intestinal permeability by upregulating the expression of intestinal tight junction proteins (TJs) and the number of goblet cells. Furthermore, dietary NOB reduced the levels of serum lipopolysaccharide (LPS) and pro-inflammatory factors (TNF-α and IL-1ß), thereby facilitating the restoration of the intestinal mucosal barrier. Additionally, dietary NOB increased the abundance of beneficial bacteria f_Lachnospiraceae and regulated the metabolic disorders of short-chain fatty acids (SCFAs) and bile acids (BAs). Notably, NOB supplementation resulted in elevated levels of butyric acid and lithocholic acid (LCA), which contributed to the repair of the intestinal mucosal barrier function and the maintenance of intestinal homeostasis. Collectively, our results propose a healthy dietary strategy for the prevention or mitigation of antibiotic-associated gut dysbiosis by dietary NOB.

Charge Characteristics of Dielectric Particle Swarm Involving Comprehensive Electrostatic Information.

The triboelectrification effect caused by dynamic contact between particles is an issue for explosions caused by electrostatic discharging (ESD) in the triboelectric nanogenerators (TENGs) for powering the flexible and wearable sensors. The electrostatic strength of dielectric particles (surface charge density, surface potential, electric field, etc.) is essential to evaluate the level of ESD risk. Those differential electrostatic characteristics concerned with unhomogenized swarmed particles cannot be offered via in-current employed-joint COMSOL 6.1 simulation, in which the discrete charged dielectric particles are mistakenly regarded as continuous ones. In this paper, the hybrid discrete element method (EDEM tool) associated with programming in COMSOL Multiphysics 6.1 with MATLAB R2023a was employed to obtain the electrostatic information of the triboelectric dielectric particle swarm. We revealed that the high-accuracy strengths of electric potential and electric field inside particle warm are crucial to evaluating ESD risk. The calculated electrostatic characteristics differ from the grid method and continuous method in the surface potential and electric field. This EDEM-based simulation method is significant for microcosmic understanding and the assessment of the ESD risk in TENGs.

Conferring liver selectivity to a thyromimetic using a novel nanoparticle increases therapeutic efficacy in a diet-induced obesity animal model.

Optimization of metabolic regulation is a promising solution for many pathologies, including obesity, dyslipidemia, type 2 diabetes, and inflammatory liver disease. Synthetic thyroid hormone mimics-based regulation of metabolic balance in the liver showed promise but was hampered by the low biocompatibility and harmful effects on the extrahepatic axis. In this work, we show that specifically directing the thyromimetic to the liver utilizing a nanogel-based carrier substantially increased therapeutic efficacy in a diet-induced obesity mouse model, evidenced by the near-complete reversal of body weight gain, liver weight and inflammation, and cholesterol levels with no alteration in the thyroxine (T4) / thyroid stimulating hormone (TSH) axis. Mechanistically, the drug acts by binding to thyroid hormone receptor ß (TRß), a ligand-inducible transcription factor that interacts with thyroid hormone response elements and modulates target gene expression. The reverse cholesterol transport (RCT) pathway is specifically implicated in the observed therapeutic effect. Overall, the study demonstrates a unique approach to restoring metabolic regulation impacting obesity and related metabolic dysfunctions.

CYP eicosanoid pathway mediates colon cancer-promoting effects of dietary linoleic acid.

Human and animal studies support that consuming a high level of linoleic acid (LA, 18:2ω-6), an essential fatty acid and key component of the human diet, increases the risk of colon cancer. However, results from human studies have been inconsistent, making it challenging to establish dietary recommendations for optimal LA intake. Given the importance of LA in the human diet, it is crucial to better understand the molecular mechanisms underlying its potential colon cancer-promoting effects. Using LC-MS/MS-based targeted lipidomics, we find that the cytochrome P450 (CYP) monooxygenase pathway is a major pathway for LA metabolism in vivo. Furthermore, CYP monooxygenase is required for the colon cancer-promoting effects of LA, since the LA-rich diet fails to exacerbate colon cancer in CYP monooxygenase-deficient mice. Finally, CYP monooxygenase mediates the pro-cancer effects of LA by converting LA to epoxy octadecenoic acids (EpOMEs), which have potent effects on promoting colon tumorigenesis via gut microbiota-dependent mechanisms. Overall, these results support that CYP monooxygenase-mediated conversion of LA to EpOMEs plays a crucial role in the health effects of LA, establishing a unique mechanistic link between dietary fatty acid intake and cancer risk. These results could help in developing more effective dietary guidelines for optimal LA intake and identifying subpopulations that may be especially vulnerable to LA's negative effects.

Adverse effects of titanium dioxide nanoparticles on beneficial gut bacteria and host health based on untargeted metabolomics analysis.

Titanium dioxide (TiO2) is a common additive in foods, medicines, and personal care products. In recent years, nano-scale particles in TiO2 additives have been an increasing concern due to their potential adverse effects on human health, especially gut health. The objective of this study was to determine the impact of titanium dioxide nanoparticles (TiO2 NPs, 30 nm) on beneficial gut bacteria and host response from a metabolomics perspective. In the in vitro study, four bacterial strains, including Lactobacillus reuteri, Lactobacillus gasseri, Bifidobacterium animalis, and Bifidobacterium longum were subjected to the treatment of TiO2 NPs. The growth kinetics, cell viability, cell membrane permeability, and metabolomics response were determined. TiO2 NPs at the concentration of 200 µg/mL showed inhibitory effects on the growth of all four strains. The confocal microscope results indicated that the growth inhibitory effects could be associated with cell membrane damage caused by TiO2 NPs to the bacterial strains. Metabolomics analysis showed that TiO2 NPs caused alterations in multiple metabolic pathways of gut bacteria, such as tryptophan and arginine metabolism, which were demonstrated to play crucial roles in regulating gut and host health. In the in vivo study, mice were fed with TiO2 NPs (0.1 wt% in diet) for 8 weeks. Mouse urine was collected for metabolomics analysis and the tryptophan metabolism pathway was also significantly affected in TiO2 NPs-fed mice. Moreover, four neuroprotective metabolites were significantly reduced in both in vitro bacteria and in vivo urine samples. Overall, this study provides insights into the potential adverse effects of TiO2 NPs on gut bacteria and the metabolic responses of both bacteria and host. Further research is needed to understand the causality between gut bacteria composition and the metabolism pathway, which is critical to monitor the gut-microbiome mediated metabolome changes in toxicological assessment of food components.

Dietary 5-demethylnobiletin prevents antibiotic-associated dysbiosis of gut microbiota and damage to the colonic barrier.

5-Demethylnobiletin (5DN) is an important ingredient of citrus extract that is rich in polymethoxyflavones (PMFs). In this study, we systemically investigated the preventive effects of 5DN on antibiotic-associated intestinal disturbances. Experimental mice were gavaged 0.2 mL per day of the antibiotic cocktail (12.5 g L-1 cefuroxime and 10 g L-1 levofloxacin) for 10 days, accompanied by dietary 0.05% 5DN for 10 and 20 days. The results showed that the combination of cefuroxime and levofloxacin caused swelling of the cecum and injury to the colon tissue. Meanwhile, the balance of intestinal oxidative stress and the barrier function of mice was also damaged by the antibiotics through upregulation of the relative mRNA levels of superoxide dismutase 3 (SOD3), quinine oxidoreductase 1 (NQO1) and glutathione peroxidase 1 (GPX1), and downregulation of the relative protein levels of tight junction proteins (TJs). Moreover, antibiotic exposure led to disorder of the gut microbiota, particularly increased harmful bacteria (Proteobacteria) and decreased beneficial bacteria (Bacteroideta). However, dietary 5DN could reduce antibiotic-associated intestinal damage, evidenced by the results that 5DN alleviated gut oxidative damage and attenuated intestinal barrier injury via increasing the expression of TJs including occludin and zonula occluden1 (ZO1). Additionally, dietary 5DN modulated the composition of the gut microbiota in antibiotic-treated mice by increasing the relative levels of beneficial bacteria, such as Dubosiella and Lactobacillus. Moreover, PMFs increased the contents of isobutyric acid and butyric acid, which were almost eliminated by antibiotic exposure. In conclusion, 5DN could alleviate antibiotic-related imbalance of intestinal oxidative stress, barrier function damage, intestinal flora disorders and the reduction of short-chain fatty acids (SCFAs), which lays a foundation for exploring safer and more effective ways to prevent or mitigate antibiotic-associated intestinal damage.

Characteristics of Mulberry Leaf Powder Enriched With γ-Aminobutyric Acid and Its Antioxidant Capacity as a Potential Functional Food Ingredient.

To improve the functional properties of mulberry leaves, γ-aminobutyric acid (GABA) enrichment treatments were applied. The results showed that the combined treatment of sodium glutamate immersion, cold shock, and anoxic significantly increased the GABA content. HPLC analysis displayed that the quantity of some active phenolics was significantly increased after the treatment. The GABA-enriched mulberry leaf powders were subsequently prepared, and it was found that as the particle size decreased, their water and oil holding capacity and their swelling power decreased, while the angle of repose increased. The dissolution rate of GABA and total phenolics increased as the particle size decreased. Optical observations and SEM results revealed that the fiber structures of the particles were gradually destroyed as the particle size decreased. Further, FTIR analysis showed that the active compounds in the powders were not destroyed. M400 and M140 powder showed the maximum DPPH radical scavenging ability and AGEs inhibition capacity, respectively. Additionally, adding the powders effectively alleviated the staling of bread without any significant effect on taste.

Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol.

Although resveratrol (RES) is barely detectable in the plasma and tissues upon oral consumption, collective evidence reveals that RES presents various bioactivities in vivo, including anti-inflammation and anti-cancer. This paradox necessitates further research on profiling and characterizing the biotransformation of RES, as its metabolites may contribute profound biological effects. After 4-week oral administration, 11 metabolites of RES were identified and quantified in mice by HPLC-MS/MS, including dihydro-resveratrol (DHR), lunularin (LUN), and conjugates (sulfates and glucuronides) of RES, DHR and LUN. Importantly, DHR, LUN, and their conjugates were much more abundantly distributed in tissues, gastrointestinal tract (GIT), and biological fluids compared to RES and its conjugates. Moreover, we established that DHR and LUN were gut bacteria-derived metabolites of RES, as indicated by their depletion in antibiotic-treated mice. Furthermore, the biological activities of RES, DHR, and LUN were determined at physiologically relevant levels. DHR and LUN exhibited stronger anti-inflammatory and anti-cancer effects than RES at the concentrations found in mouse tissues. In summary, our study profiled the tissue distribution of the metabolites of RES after its oral administration in mice and uncovered the important role of gut microbial metabolites of RES in the biological activities of RES in vivo.

Dietary Boswellia serrata Acid Alters the Gut Microbiome and Blood Metabolites in Experimental Models.

Boswellia serrata, commonly known as frankincense, has been used for centuries as a natural anti-inflammatory and anti-microbial remedy for many illnesses. However, the effect of the bioactive ingredient of it, 3-O-acetyl-11-keto-b-boswellic acid (AKBA), on both the gut microbiome and blood metabolites, is not known. In this study, we observe the effect of this isolated active ingredient orally on both male and female mice. Gut microbiota and blood metabolites were determined at the beginning and end of a 14-day consumption period. AKBA significantly decreased gut bacterial richness in male mice, and had no effect on female mice. Akkermansia muciniphila, associated with weight loss and anti-inflammation, was found to be significantly increased in both male and female mice, along with an increase in Bifidobacterium in female mice. Akkermansia muciniphila and Bifidobacterium were plated on media containing varying levels of AKBA (0%, 0.001%, 0.01%, and 0.1%). All concentrations of AKBA completely inhibited growth of Akkermansia muciniphila but had no effect on Bifidobacterium. Several blood metabolites differed with AKBA between both males and females. These results show the potential benefits of dietary Boswellia serrata on the modulation of gut microbiome composition, along with differences between sexes.

Alterations of host-gut microbiome interactions in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder. METHODS: We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. Circulating metabolites were profiled by untargeted UPLC-MS. A four-day food diary was recorded to capture the habitual dietary pattern of study participants. FINDINGS: Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. The microbiome and metabolome profiles remained stable over six months in MS and control individuals. INTERPRETATION: Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. FUNDING: This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Adverse effects of linoleic acid: Influence of lipid oxidation on lymphatic transport of citrus flavonoid and enterocyte morphology.

Lipids usually contain a large ratio of polyunsaturated fatty acids (PUFAs), which are highly susceptible to oxidation. Presence of oxidized lipids in foods may affect the bioavailability of lipophilic bioactive components after ingestion. In this study, the effect of oxidized and unoxidized linoleic acid (LA) on the transport of a highly lipophilic bioactive citrus flavonoid (5-hydroxy - 6, 7, 8, 4' tetramethoxylflavone or 5-DMT) was determined using a Caco-2 cell model. Results demonstrated that compared to free 5-DMT, unoxidized LA improved the trans-enterocyte absorption of 5-DMT by stimulating the production of lipid droplets and chylomicrons. Although the amount of 5-DMT transported across the enterocyte doubled by oxidized LA compared to free 5-DMT, it significantly induced reactive oxygen species (ROS), affected the function of tight junction and caused damages to the morphology of enterocyte monolayer. This study re-emphasized the importance of preventing lipid oxidation in foods.

Protective effects of non-extractable phenolics from strawberry against inflammation and colon cancer in vitro.

Strawberry is a rich source of phenolics. However, most studies focused on extractable phenolics (EP) while neglecting non-extractable phenolics (NEP). The aim of this study was to characterize EP and NEP from strawberry (Fragaria × ananassa) and determine their anti-inflammatory and anti-colon cancer potentials in cell culture models. NEP contained flavonols, flavanols and phenolic acids that were released through alkaline hydrolysis. NEP dose-dependently inhibited lipopolysaccharides -induced NO production in RAW 264.7 macrophage. Western blotting showed that NEP reduced the expression levels of pro-inflammatory proteins such as iNOS and c-FOS, but increased the expression level of antioxidative protein, such as HO-1. Moreover, NEP markedly suppressed proliferation of human colon cancer HCT116 cells via inducing G2/M phase cell cycle arrest and apoptosis. Collectively, these findings illustrated preventive effects of strawberry NEP against inflammation and colon cancer, shedding light on potential contribution of NEP from strawberry as a health-promoting agent.