The Effect of Oil-Based Cannabis Extracts on Metabolic Parameters and Microbiota Composition of Mice Fed a Standard and a High-Fat Diet.

The prevalence of obesity and obesity-related pathologies is lower in frequent cannabis users compared to non-users. It is well established that the endocannabinoid system has an important role in the development of obesity. We recently demonstrated that prolonged oral consumption of purified Δ-9 Tetrahydrocannabinol (THC), but not of cannabidiol (CBD), ameliorates diet-induced obesity and improves obesity-related metabolic complications in a high-fat diet mouse model. However, the effect of commercially available medical cannabis oils that contain numerous additional active molecules has not been examined. We tested herein the effects of THC- and CBD-enriched medical cannabis oils on obesity parameters and the gut microbiota composition of C57BL/6 male mice fed with either a high-fat or standard diet. We also assessed the levels of prominent endocannabinoids and endocannabinoid-like lipid mediators in the liver. THC-enriched extract prevented weight gain by a high-fat diet and attenuated diet-induced liver steatosis concomitantly with reduced levels of the lipid mediators palmitoyl ethanolamide (PEA) and docosahexaenoyl ethanolamide (DHEA) in the liver. In contrast, CBD-enriched extract had no effect on weight gain, but, on the contrary, it even exacerbated liver steatosis. An analysis of the gut microbiota revealed that mainly time but not treatment exerted a strong effect on gut microbiota alterations. From our data, we conclude that THC-enriched cannabis oil where THC is the main constituent exerts the optimal anti-obesity effects.

Phytocannabinoids Reduce Inflammation of Primed Macrophages and Enteric Glial Cells: An In Vitro Study.

Intestinal inflammation is mediated by a subset of cells populating the intestine, such as enteric glial cells (EGC) and macrophages. Different studies indicate that phytocannabinoids could play a possible role in the treatment of inflammatory bowel disease (IBD) by relieving the symptoms involved in the disease. Phytocannabinoids act through the endocannabinoid system, which is distributed throughout the mammalian body in the cells of the immune system and in the intestinal cells. Our in vitro study analyzed the putative anti-inflammatory effect of nine selected pure cannabinoids in J774A1 macrophage cells and EGCs triggered to undergo inflammation with lipopolysaccharide (LPS). The anti-inflammatory effect of several phytocannabinoids was measured by their ability to reduce TNFα transcription and translation in J774A1 macrophages and to diminish S100B and GFAP secretion and transcription in EGCs. Our results demonstrate that THC at the lower concentrations tested exerted the most effective anti-inflammatory effect in both J774A1 macrophages and EGCs compared to the other phytocannabinoids tested herein. We then performed RNA-seq analysis of EGCs exposed to LPS in the presence or absence of THC or THC-COOH. Transcriptomic analysis of these EGCs revealed 23 differentially expressed genes (DEG) compared to the treatment with only LPS. Pretreatment with THC resulted in 26 DEG, and pretreatment with THC-COOH resulted in 25 DEG. To evaluate which biological pathways were affected by the different phytocannabinoid treatments, we used the Ingenuity platform. We show that THC treatment affects the mTOR and RAR signaling pathway, while THC-COOH mainly affects the IL6 signaling pathway.

The Effect of Orally Administered Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) on Obesity Parameters in Mice.

Prolonged cannabis users show a lower prevalence of obesity and associated comorbidities. In rodent models, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) from the plant Cannabis sativa L. have shown anti-obesity properties, suggesting a link between the endocannabinoid system (ECS) and obesity. However, the oral administration route has rarely been studied in this context. The aim of this study was to investigate the effect of prolonged oral administration of pure THC and CBD on obesity-related parameters and peripheral endocannabinoids. C57BL/6 male mice were fed with either a high-fat or standard diet and then received oral treatment in ramping doses, namely 10 mg/kg of THC or CBD for 5 weeks followed by 30 mg/kg for an additional 5 weeks. Mice treated with THC had attenuated weight gain and improved glucose tolerance, followed by improvement in steatosis markers and decreased hypertrophic cells in adipose epididymal tissue. Mice treated with CBD had improved glucose tolerance and increased markers of lipid metabolism in adipose and liver tissues, but in contrast to THC, CBD had no effect on weight gain and steatosis markers. CBD exclusively decreased the level of the endocannabinoid 2-arachidonoylglycerol in the liver. These data suggest that the prolonged oral consumption of THC, but not of CBD, ameliorates diet-induced obesity and metabolic parameters, possibly through a mechanism of adipose tissue adaptation.

Anti-Inflammatory Activity of Black Soldier Fly Oil Associated with Modulation of TLR Signaling: A Metabolomic Approach.

Dietary intervention in the treatment of ulcerative colitis involves, among other things, modifications in fatty acid content and/or profile. For example, replacing saturated long chain fatty acids with medium chain fatty acids (MCFAs) has been reported to ameliorate inflammation. The Black Soldier Fly Larvae's (BSFL) oil is considered a sustainable dietary ingredient rich in the MCFA C12:0; however, its effect on inflammatory-related conditions has not been studied until now. Thus, the present study aimed to investigate the anti-inflammatory activity of BSFL oil in comparison to C12:0 using TLR4- or TLR2-activated THP-1 and J774A.1 cell lines and to assess its putative protective effect against dextran sulfate sodium (DSS)-induced acute colitis in mice. BSFL oil and C12:0 suppressed proinflammatory cytokines release in LPS-stimulated macrophages; however, only BSFL oil exerted anti-inflammatory activity in Pam3CSK4-stimulated macrophages. Transcriptome analysis provided insight into the possible role of BSFL oil in immunometabolism switch, involving mTOR signaling and an increase in PPAR target genes promoting fatty acid oxidation, exhibiting a discrepant mode of action compared to C12:0 treatment, which mainly affected cholesterol biosynthesis pathways. Additionally, we identified anti-inflammatory eicosanoids, oxylipins, and isoprenoids in the BSFL oil that may contribute to an orchestrated anti-inflammatory response. In vivo, a BSFL oil-enriched diet (20%) ameliorated the clinical signs of colitis, as indicated by improved body weight recovery, reduced colon shortening, reduced splenomegaly, and an earlier phase of secretory IgA response. These results indicate the novel beneficial use of BSFL oil as a modulator of inflammation.

Human Milk Oligosaccharide Profile across Lactation Stages in Israeli Women-A Prospective Observational Study.

Human milk oligosaccharides (HMOs) stimulate the growth of gut commensals, prevent the adhesion of enteropathogens and modulate host immunity. The major factors influencing variations in the HMO profile are polymorphisms in the secretor (Se) or Lewis (Le) gene, which affect the activity of the enzymes fucoslytransferase 2 and 3 (FUT2 and FUT3) that lead to the formation of four major fucosylated and non-fucosylated oligosaccharides (OS). This pilot study aimed to determine the HMO profile of Israeli breastfeeding mothers of 16 term and 4 preterm infants, from a single tertiary center in the Tel Aviv area. Fifty-two human milk samples were collected from 20 mothers at three-time points: colostrum, transitional milk and mature milk. The concentrations of nine HMOs were assessed using liquid chromatography coupled with mass spectra chromatograms. Fifty-five percent of the mothers were secretors and 45% were non-secretors. Infant sex affected HMO levels depending on the maternal secretor status. Secretor mothers to boys had higher levels of FUT2-dependent OS and higher levels of disialyllacto-N-tetraose in the milk of mothers to girls, whereas non-secretor mothers to girls had higher levels of 3'-sialyllactose. In addition, the season at which the human milk samples were obtained affected the levels of some HMOs, resulting in significantly lower levels in the summer. Our findings provide novel information on the irregularity in the HMO profile among Israeli lactating women and identify several factors contributing to this variability.

"Residential greenness, gestational diabetes mellitus (GDM) and microbiome diversity during pregnancy".

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with reduced gut microbiota richness that was also reported to differ significantly between those living in rural compared to urban environments. Therefore, our aim was to examine the associations between greenness and maternal blood glucose levels and GDM, with microbiome diversity as a possible mediator in these associations. METHODS: Pregnant women were recruited between January 2016 and October 2017. Residential greenness was evaluated as mean Normalized Difference Vegetation Index (NDVI) within 100, 300 and 500 m buffers surrounding each maternal residential address. Maternal glucose levels were measured at 24-28 weeks of gestation and GDM was diagnosed. We estimated the associations between greenness and glucose levels and GDM using generalized linear models, adjusting for socioeconomic status and season at last menstrual period. Using causal mediation analysis, the mediation effects of four different indices of microbiome alpha diversity in first trimester stool and saliva samples were assessed. RESULTS: Of 269 pregnant women, 27 participants (10.04%) were diagnosed with GDM. Although not statistically significant, adjusted exposure to medium tertile levels of mean NDVI at 300 m buffer had lower odds of GDM (OR = 0.45, 95% CI: 0.16, 1.26, p = 0.13) and decreased change in mean glucose levels (ß = -6.28, 95% CI: 14.91, 2.24, p = 0.15) compared to the lowest tertile levels of mean NDVI. Mixed results were observed at 100 and 500 m buffers, and when comparing highest tertile levels to lowest. No mediation effect of first trimester microbiome on the association between residential greenness and GDM was observed, and a small, possibly incidental, mediation effect on glucose levels was observed. CONCLUSION: Our study suggests possible associations between residential greenness and glucose intolerance and risk of GDM, though without sufficient evidence. Microbiome in the first trimester, while involved in GDM etiology, is not a mediator in these associations. Future studies in larger populations should further examine these associations.

The Effect of Bioactive Aliment Compounds and Micronutrients on Non-Alcoholic Fatty Liver Disease.

In the current review, we focused on identifying aliment compounds and micronutrients, as well as addressed promising bioactive nutrients that may interfere with NAFLD advance and ultimately affect this disease progress. In this regard, we targeted: 1. Potential bioactive nutrients that may interfere with NAFLD, specifically dark chocolate, cocoa butter, and peanut butter which may be involved in decreasing cholesterol concentrations. 2. The role of sweeteners used in coffee and other frequent beverages; in this sense, stevia has proven to be adequate for improving carbohydrate metabolism, liver steatosis, and liver fibrosis. 3. Additional compounds were shown to exert a beneficial action on NAFLD, namely glutathione, soy lecithin, silymarin, Aquamin, and cannabinoids which were shown to lower the serum concentration of triglycerides. 4. The effects of micronutrients, especially vitamins, on NAFLD. Even if most studies demonstrate the beneficial role of vitamins in this pathology, there are exceptions. 5. We provide information regarding the modulation of the activity of some enzymes related to NAFLD and their effect on this disease. We conclude that NAFLD can be prevented or improved by different factors through their involvement in the signaling, genetic, and biochemical pathways that underlie NAFLD. Therefore, exposing this vast knowledge to the public is particularly important.

Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.

B Vitamins, Glucoronolactone and the Immune System: Bioavailability, Doses and Efficiency.

The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a strong relationship between the recommended daily dose of selected B vitamins and a functional immune system. Regarding specific B vitamins: (1) Riboflavin is necessary for the optimization of reactive oxygen species (ROS) in the fight against bacterial infections caused by Staphylococcus aureus and Listeria monocytogenes. (2) Niacin administered within normal doses to obese rats can change the phenotype of skeletal fibers, and thereby affect muscle metabolism. This metabolic phenotype induced by niacin treatment is also confirmed by stimulation of the expression of genes involved in the metabolism of free fatty acids (FFAs) and oxidative phosphorylation at this level. (3) Vitamin B5 effects depend primarily on the dose, thus large doses can cause diarrhea or functional disorders of the digestive tract whereas normal levels are effective in wound healing, liver detoxification, and joint health support. (4) High vitamin B6 concentrations (>2000 mg per day) have been shown to exert a significant negative impact on the dorsal root ganglia. Whereas, at doses of approximately 70 ng/mL, sensory symptoms were reported in 80% of cases. (5) Chronic increases in vitamin B12 have been associated with the increased incidence of solid cancers. Additionally, glucuronolactone, whose effects are not well known, represents a controversial compound. (6) Supplementing with D-glucarates, such as glucuronolactone, may help the body's natural defense system function better to inhibit different tumor promoters and carcinogens and their consequences. Cumulatively, the present review aims to evaluate the relationship between the selected B vitamins group, glucuronolactone, and the immune system and their associations to bioavailability, doses, and efficiency.

The relationship between nutrition and the immune system.

Nutrition plays an essential role in the regulation of optimal immunological response, by providing adequate nutrients in sufficient concentrations to immune cells. There are a large number of micronutrients, such as minerals, and vitamins, as well as some macronutrients such as some amino acids, cholesterol and fatty acids demonstrated to exert a very important and specific impact on appropriate immune activity. This review aims to summarize at some extent the large amount of data accrued to date related to the modulation of immune function by certain micro and macronutrients and to emphasize their importance in maintaining human health. Thus, among many, some relevant case in point examples are brought and discussed: (1) The role of vitamin A/all-trans-retinoic-acids (ATRA) in acute promyelocytic leukemia, being this vitamin utilized as a very efficient therapeutic agent via effective modulation of the immune function (2) The involvement of vitamin C in the fight against tumor cells via the increase of the number of active NK cells. (3) The stimulation of apoptosis, the suppression of cancer cell proliferation, and delayed tumor development mediated by calcitriol/vitamin D by means of immunity regulation (4) The use of selenium as a cofactor to reach more effective immune response to COVID vaccination (5). The crucial role of cholesterol to regulate the immune function, which is demonstrated to be very sensitive to the variations of this macronutrient concentration. Other important examples are reviewed as well.

Critical Sites on Ostreolysin Are Responsible for Interaction with Cytoskeletal Proteins.

We explored the structural features of recombinant ostreolysin A (rOlyA), a protein produced by Pleurotus ostreatus and responsible for binding to α/ß-tubulin. We found that rOlyA cell internalization is essential for the induction of adipocyte-associated activity, which is mediated by the interaction of rOlyA and microtubule proteins. We created different point mutations at conserved tryptophan (W) sites in rOlyA and analyzed their biological activity in HIB-1B preadipocytes. We demonstrated that the protein's cell-internalization ability and the differentiated phenotype induced, such as small lipid-droplet formation and gene expression of mitogenesis activity, were impaired in point-mutated proteins W96A and W28A, where W was converted to alanine (A). We also showed that an rOlyA homologue, OlyA6 complexed with mCherry, cannot bind to ß-tubulin and does not induce mitochondrial biosynthesis-associated markers, suggesting that the OlyA6 region masked by mCherry is involved in ß-tubulin binding. Protein-protein docking simulations were carried out to investigate the binding mode of rOlyA with ß-tubulin. Taken together, we identified functional sites in rOlyA that are essential for its binding to ß-tubulin and its adipocyte-associated biological activity.

A Case-Control Study Examining the Association of Fiber, Fruit, and Vegetable Intake and the Risk of Colorectal Cancer in a Palestinian Population.

While there is an association between Western diets and the incidence of colorectal cancer (CRC), this dietary association has remained unexplored in Palestine. The aim of this study was to examine how fiber and fruit and vegetable (FV) intakes are associated with CRC risk among Palestinian adults. We recruited 528 Palestinians between 2014 and 2016. We identified 118 patients who received CRC treatment at Augusta Victoria Hospital, East Jerusalem. We additionally identified 410 controls who consisted of community-based Palestinians without cancer. All participants completed a survey on demographics and a validated dietary intake food screener. Multivariable logistic regression models tested associations between fiber and FV intakes (categorized into quartiles) with CRC risk. After adjusting for significant covariates (age, sex, education, physical activity, smoking status, BMI, IBD, and family history of CRC), as fibers increased across increasing quartiles, the CRC risk significantly decreased (OR = 0.36, 95% CI: 0.15-0.86, p-trend = 0.02). After adjusting for age and sex, as FV intake increased, the CRC risk significantly decreased (OR = 0.34, 95% CI: 0.15-0.75, p-trend = 0.009). Consumption of fiber-rich foods was inversely associated with CRC risk. Understanding this relationship among Palestinians is essential in order to develop targeted, culturally relevant strategies that may potentially alleviate the burden of CRC.

Beta-glucans induce cellular immune training and changes in intestinal morphology in poultry.

Introduction: Beta-glucans are known as biological response modifiers due to their ability to activate the immune system. This research aimed to determine the efficacy and safety of feeding beta-glucans from various sources on the immune status and intestinal morphology of chickens. Methods: To this end we used in vitro and in vivo set-ups. In the in vitro set-up the chicken macrophage cell line HD-11 was used to measure the response of the chicken immune cells to beta-glucans extracted from algae and mushrooms on immune-related gene expression and associated activities. Additionally, we conducted two in vivo experiments using either beta-glucans extracted from yeast or mix of yeast and mushrooms beta-glucans as part of the chicks feed in order to test their effects on the chick intestinal morphology. Results: In the in vitro set-up exposure of HD-11 cells to a concentration of 1 mg/ml of algae and mushroom beta-glucans resulted in significantly higher expression of 6 genes (TNFα, IL4, IL6, IL8, IL10, and iNOS2) compared to control. The release of nitrite oxide (NO) to the medium after exposure of HD-11 cells to mushrooms or algae beta-glucans was significantly increased compared to control. Additionally, significantly increased phagocytosis activity was found after exposure of the cells to algae and mushroom beta-glucans. In the in vivo set-up we observed that the length of the villi and the number of goblet cells in the ileum and the jejunum in the beta-glucan fed chicks were significantly augmented compared to control, when the chicks were fed with either yeast or yeast and mushroom beta-glucans mix. Discussion: In conclusion, dietary supplementation of poultry with beta-glucan exerts significant and positive effects on immune activity and the intestinal morphology in poultry.

Review: ß-glucans as Effective Antibiotic Alternatives in Poultry.

The occurrence of microbial challenges in commercial poultry farming causes significant economic losses. Antibiotics have been used to control diseases involving bacterial infection in poultry. As the incidence of antibiotic resistance turns out to be a serious problem, there is increased pressure on producers to reduce antibiotic use. With the reduced availability of antibiotics, poultry producers are looking for feed additives to stimulate the immune system of the chicken to resist microbial infection. Some ß-glucans have been shown to improve gut health, to increase the flow of new immunocytes, increase macrophage function, stimulate phagocytosis, affect intestinal morphology, enhance goblet cell number and mucin-2 production, induce the increased expression of intestinal tight-junctions, and function as effective anti-inflammatory immunomodulators in poultry. As a result, ß-glucans may provide a new tool for producers trying to reduce or eliminate the use of antibiotics in fowl diets. The specific activity of each ß-glucan subtype still needs to be investigated. Upon knowledge, optimal ß-glucan mixtures may be implemented in order to obtain optimal growth performance, exert anti-inflammatory and immunomodulatory activity, and optimized intestinal morphology and histology responses in poultry. This review provides an extensive overview of the current use of ß glucans as additives and putative use as antibiotic alternative in poultry.

Whole body metabolism is improved by hemin added to high fat diet while counteracted by nitrite: a mouse model of processed meat consumption.

Nitrites and nitrates are traditional food additives used as curing agents in the food industry. They inhibit the growth of microorganisms and give a typical pink color to meat. Besides the positive effects of nitrite in foods, if present at high levels in the body, may induce hypoxia and contribute to the production of pro-carcinogenic secondary N-nitrosamines. This study investigated the whole-body metabolic effects of hemin and nitrite added to a high fat diet as red and processed red meat nutritional models. Mice were fed for 11 weeks with five different diets-(1) control diet (ND), (2) high fat diet (HFD) with 60% fat, (3) HFD with hemin (HFD + H, red meat model), (4) HFD with hemin and nitrite (HFD + HN, processed meat model), and (5) HFD with hemin, nitrite, and secondary amine (HFD + HNN, N-nitrosamine generating model)-and several metabolic parameters were determined and respiratory measurements were performed. Mice fed with the HFD + H or HFD + HNN diet had a lower epididymal white adipose tissue (eWAT) : body ratio and lower fasting glucose level than those fed the HFD alone. In addition, our results demonstrated a relief in hepatosteatosis grade among the HFD + H and HFD + HNN diet fed mice. Nitrite added to the HFD impaired the ability to use fat for energy, opposite to the effect of hemin. This study shows that nitrite in addition to pro-carcinogenesis and hypoxia can impact metabolic disease progression when added to meat.

The Role of Omega-3 Polyunsaturated Fatty Acids from Different Sources in Bone Development.

N-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained from the diet. We have previously showed that endogenous n-3 PUFAs contribute to skeletal development and bone quality in fat-1 mice. Unlike other mammals, these transgenic mice, carry the n-3 desaturase gene and thus can convert n-6 to n-3 PUFAs endogenously. Since this model does not mimic dietary exposure to n-3 PUFAs, diets rich in fish and flaxseed oils were used to further elucidate the role of n-3 PUFAs in bone development. Our investigation reveals that dietary n-3 PUFAs decrease fat accumulation in the liver, lower serum fat levels, and alter fatty acid (FA) content in liver and serum. Bone analyses show that n-3 PUFAs improve mechanical properties, which were measured using a three-point bending test, but exert complex effects on bone structure that vary according to its source. In a micro-CT analysis, we found that the flaxseed oil diet improves trabecular bone micro-architecture, whereas the fish oil diet promotes higher bone mineral density (BMD) with no effect on trabecular bone. The transcriptome characterization of bone by RNA-seq identified regulatory mechanisms of n-3 PUFAs via modulation of the cell cycle and peripheral circadian rhythm genes. These results extend our knowledge and provide insights into the molecular mechanisms of bone remodeling regulation induced by different sources of dietary n-3 PUFAs.

Nitrogen availability and genotype affect major nutritional quality parameters of tef grain grown under irrigation.

Worldwide demand for tef (Eragrostis tef) as a functional food for human consumption is increasing, thanks to its nutritional benefits and gluten-free properties. As a result, tef in now grown outside its native environment in Ethiopia and thus information is required regarding plant nutrition demands in these areas, as well as resulting grain health-related composition. In the current work, two tef genotypes were grown in Israel under irrigation in two platforms, plots in the field and pots in a greenhouse, with four and five nitrogen treatments, respectively. Nutritional and health-related quality traits were analyzed, including mineral content, fatty acid composition, hydrophilic and lipophilic antioxidative capacity, total phenolic content and basic polyphenolic profile. Our results show that tef genotypes differ in their nutritional composition, e.g. higher phenolic contents in the brown compared to the white genotype. Additionally, nitrogen availability positively affected grain fatty acid composition and iron levels in both experiments, while negatively affecting total phenolics in the field trials. To conclude, nitrogen fertilization is crucial for crop growth and productivity, however it also implicates nutritional value of the grains as food. These effects should be considered when fertilizing tef with nitrogen, to optimize both crop productivity and nutritional effects.

Immunomodulating Effects Exerted by Glucans Extracted from the King Oyster Culinary-Medicinal Mushroom Pleurotus eryngii (Agaricomycetes) Grown in Substrates Containing Various Concentrations of Olive Mill Waste.

We have recently demonstrated that we could enhance glucan content in Pleurotus eryngii following cultivation of the mushrooms on a substrate containing different concentrations of olive mill solid waste (OMSW). These changes are directly related to the content of OMSW in the growing substrate. Using dextran sulfate sodium (DSS)-in-flammatory bowel disease (IBD) mice model, we measured the colonic inflammatory response to the different glucan preparations. We found that the histology damaging score (HDS) resulting from DSS treatment reach a value of 11.8 ± 2.3 were efficiently downregulated by treatment with the fungal extracted glucans. Glucans extracted from stalks cultivated at 20% OMSW downregulated to a HDS value of 6.4 ± 0.5 whereas those cultivated at 80% OMSW showed the strongest effects (5.5 ± 0.6). Similar downregulatory effects were obtained for expression of various intestinal cytokines. All tested glucans were equally effective in regulating the number of CD14/CD16 monocytes from 18.2 ± 2.7% for DSS to 6.4 ± 2.0 for DSS + glucans extracted from stalks cultivated at 50% OMSW. We tested the effect of glucans on lipopolysaccharide-induced production of TNF-α, which demonstrated that stalk-derived glucans were more effective than caps-derived glucans. Isolated glucans competed with anti-Dectin-1 and anti-CR3 antibodies, indicating that they contain ß-glucans recognized by these receptors. In conclusion, the most effective glucans in ameliorating IBD-associated symptoms induced by DSS treatment in mice were glucan extracts prepared from the stalk of P. eryngii grown at higher concentrations of OMSW. We conclude that these stress-induced growing conditions may be helpful in selecting more effective glucans derived from edible mushrooms.

Adipocytes Isolated from Visceral and Subcutaneous Depots of Donors Differing in BMI Crosstalk with Colon Cancer Cells and Modulate their Invasive Phenotype.

PURPOSE: Mechanisms related the crosstalk between adipocytes and colon cancer cells are still not clear. We hypothesize that molecules and adipocytokines generated from the adipose tissue of obese individuals accentuate the effect on the metabolic reprogramming in colon cancer cells, i.e. induce disarray in energy metabolism networks of the targeted affected colonic epithelial cells, prompting their malignant phenotype. METHODS: To explore the mechanistic behind this crosstalk we conducted a co-culture model system using human colon cancer cells having different malignant abilities and adipocytes from different depots and subjects. RESULTS: The results demonstrate that co-culturing aggressive colon cancer cells such as HM-7 cells, with Visceral or Subcutaneous adipocytes (VA or SA respectively) from lean/obese subjects significantly up-regulate the secretion of the adipokines IL-8, MCP1, and IL-6 from the adipocytes. Surprisingly, the response of co-culturing HM-7 cells with obese SA was substantially more significant. In addition, these effects were significantly more pronounced when using HM-7 cells as compared to the less malignant HCT116 colon cancer cells. Moreover, the results showed that HM-7 cells, co-cultured with VA or SA from obese subjects, expressed higher levels of fatty acid binding protein 4; thus, the conditioned media obtained from the wells contained HM-7 cells and adipocytes from obese subjects was significantly more efficient in promoting invasion of HM-7 cells. CONCLUSIONS: We conclude that interaction between adipocytes and colon cancer cells, especially the highly malignant cells, results in metabolic alterations in colon cancer cells and in highly hypertrophy phenotype which characterized by increasing adipokines secretion from the adipocytes.