Pro- and Antioxidant Effect of Food Items and Matrices during Simulated In Vitro Digestion

The digestive tract can be considered a bioreactor. High levels of reactive oxygen species (ROS) during digestion may predispose for local and/or systemic oxidative stress and inflammation, e.g., inflammatory bowel diseases. Food items rich in antioxidants may prevent such aggravation. This investigation analyzed pro-and antioxidant patterns of food matrices/items following in vitro digestion. Gastrointestinal digestion reflecting typically consumed quantities was performed on nine food items (orange and tomato juice, soda, coffee, white chocolate, sausage, vitamin C and E, and curcumin) and their combinations (n = 24), using the INFOGEST model. Antioxidant potential was measured by FRAP, DPPH, and ABTS, and pro-oxidant aspects by MDA (malondialdehyde) and peroxide formation. An anti-pro-oxidant score was developed, combining the five assays. Liquid food items showed moderately high antioxidant values, except for coffee and orange juice, which exhibited a high antioxidant potential. Solid matrices, e.g., white chocolate and sausage, showed both high pro-oxidant (up to 22 mg/L MDA) and high antioxidant potential (up to 336 mg/L vitamin C equivalents) at the same time. Individual vitamins (C and E) at physiological levels (achievable from food items) showed a moderate antioxidant potential (<220 mg/L vitamin C equivalents). Overall, both antioxidant and pro-oxidant assays correlated well, with correlation coefficients of up to 0.894. The effects of food combinations were generally additive, i.e., non-synergistic, except for combinations with sausage, where strong quenching effects for MDA were observed, e.g., with orange juice. In conclusion, as especially highlighted by complex matrices demonstrating both pro- and antioxidant potential, only measuring one aspect would result in physiological misinterpretations. Therefore, it is imperative to employ a combination of assays to evaluate both pro- and antioxidant properties of food digesta to ensure physiological relevance

Effect of Digested Selected Food Items on Markers of Oxidative Stress and Inflammation in a Caco-2-Based Human Gut Epithelial Model

The human gut epithelium presents a crucial interface between ingested food items and the host. Understanding how different food items influence oxidative stress and inflammation in the gut is of great importance. This study assessed the impact of various digested food items on oxidative stress, inflammation, and DNA/RNA damage in human gut epithelial cells. Differentiated Caco-2 cells were exposed to food items and their combinations (n = 22) selected from a previous study, including sausage, white chocolate, soda, coffee, orange juice, and curcumin. Following stimulation with TNF-α/IFN-1β/LPS and H2O2 for 4 h, the cells were exposed to digested food items or appropriate controls (empty digesta and medium) for a further 16 h. Cell viability, antioxidant capacity (ABTS, FRAP), IL-6, IL-8, F2-isoprostanes, lipid peroxidation (MDA), and DNA/RNA oxidative damage were assessed (3 independent triplicates). The ABTS assay revealed that cells treated with “white chocolate” and “sausage + coffee” exhibited significantly reduced antioxidant capacity compared to stimulated control cells (ABTS = 52.3%, 54.8%, respectively, p p p < 0.05) compared to stimulated control cells. This investigation provides insights into how different food items may affect gut health and underscores the complex interplay between food components and the epithelium at this critical interface of absorption

Valproic Acid Induces Non Apoptotic Cell Death in Myeloma Cells and Cell Lines.

Abstract Multiple myeloma is, despite the emergence of new treatment strategies in recent years, still a lethal disease in 2005. Over the last several years, significant insights into the dysregulation of various signal transduction pathways of MM have emerged and have evolved the development of new agents. Histone deacetylase inhibitors as valproic acid are compounds that inhibit HDACs enzymes that, in conjunction with histone acetylases, regulate the acetylation state of histones and, by extension, the conformational status of chromatin. VPA is clinically known to be used in treatment of different types of epileptic disease. Effects and signal transduction pathways of cell death have been studied in cells harvested and purified from routine bone marrow aspirates of several patients with multiple myeloma, as well as on myeloma cell lines (OPM2, U266) treated with a physiologic dose range of valproic acid (1–4 mM). We observe significant in vitro toxicity starting at doses of 1 mM for 24h in cell lines as well as in patient cells using an XTT based cytotoxicity assay. The question we adressed was the mechanisms by which the MM died. Flow cytometric analysis with PI / Annexin V staining does not show apoptosis features, nor do TUNEL staining or DNA fragmentation assays, suggesting non activation of the intrinsic apoptosis pathway. In contrast, cell morphology of treated cells stained with May-Gruenwald-Giemsa staining show increase in multinucleated giant cells. Multinucleation has often been described in cells which die through mitotic catastrophe. Further experiments exploring this hypothesis will be conducted. Effect of 48h valproic ac on myeloma cell lines Effect of 48h valproic ac on myeloma cell lines Effect of 48h valproic ac on CD138 cells from myeloma patients Effect of 48h valproic ac on CD138 cells from myeloma patients</jats:p

Multidisciplinary management of obesity through digital-health: a scoping review.

A scoping review will be conducted in order to summarise the available evidence on digital health and multidisciplinary management of obesity including overweight. Studies will be selected if the obesity management is based on nutrition education, promotion of regular physical activity and/or psychological support through digital health. The PRISMA-ScR checklist (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Review) will be followed. - Hypotheses and objectives: Obesity is a multifactorial disease. Multidisciplinary approaches based on nutrition education, promotion of regular physical activity and/or psychological support provide an optimal management of obesity (1-4). As digital health enables people to manage their own health, digital health technologies might sustainably help to take charge of obesity (5, 6). The objective of the scoping review is to summarise the available evidence on multidisciplinary management of obesity through digital health, based on nutritional, exercise and/or psychological support. - Design Plan: +Study type: Scoping review. +Study design: Scoping review based on a systematic search of evidence. The evidence will include observational (i.e. cross-sectional, case-control studies and cohorts) and experimental (i.e. randomised controlled trials or non-randomised trials) studies. - Sampling Plan: +Existing Data: The present study corresponds to the first research conducted by our group in this domain. +Explanation of existing data: Understanding on the existing data has been limited to exploratory non-systematic searches of reviews and studies using PubMed. - Data collection procedures: +Eligibility criteria: Studies published in English since January 1st 2000 will be considered. Studies will be selected if they consider the management of obesity as a disease through digital health in humans. Eligible studies will have information on the multidisciplinary management of obesity, including overweight, through nutrition education, physical activity promotion and/or psychological support through digital health technologies. Original research will be eligible. Brief reports, reviews and commentaries will be considered as a potential source of references not found in our systematic search. The age range of inclusion will be between 6 and 64 years old: children (6-12 years), adolescents (13-18 years), adults (19-44 years) and people at middle age (45-64 years) having overweight or obesity. +Exclusion criteria: Children and adults with normal weight (without overweight or obesity), Children &lt; 6 years, Elderly people (≥ 65 years), Studies targeting the management of other chronic diseases than obesity as primary outcome (e.g. cardiovascular disease, diabetes, cancer, hypertension…). In these studies, obesity is not considered as a disease, but as a risk factor of the other chronic diseases, Pregnancy, Articles published languages other than English, “Grey” literature (reports, doctoral theses, conference contributions, book chapters, editorials), unless they will be used to identify potential references. - Systematic search: 1. An exhaustive systematic search of the literature will be performed through the following selected databases: +PubMed covering all records from Medline, as well as in-processing publications, + Scopus covering all records from PsycINFO and Web of Science, in addition to Medline records. + If needed we will contact colleagues working on the topic of interest to ask to them for potential relevant material. 2. Joanna Briggs Manual: The scoping review will be performed according to the Joanna Briggs Manual: + Identification of key words An initial limited search in 20 previously published papers will be performed. This will enable us to identify the main keywords and synonyms associated with the topic. These keywords will be extracted from the title, abstract and the main text of the selected articles. A snowball search will be performed, based on the references cited in the selected papers. The 20 most significant studies will be selected from the snowball search. A MeSH (Medical Subject Headings) terms search will also be conducted. + Execution of systematic search: The systematic final search will be conducted, in the selected databases, based on the combination of the selected keywords. The search strategy will have the following structure: “keywords for obesity” AND “keywords for digital health” AND “keywords for nutritional education OR promotion of physical activity OR psychological support”. The full electronic search strategy will be presented in the appendix of the final manuscript. + Data charting process: The open access online software CADIMA (JKI—Julius Kühn-Institut, vers. 2.1.3 - Feb 2020) will be used to conduct the systematic search. ++ Papers selection: The literature search will be uploaded from the PubMed and Scopus databases into the software CADIMA as a bibliographic citation file that will be registered in RIS (Research Information Systems) format. The search results will then be combined. The duplicated studies will be detected and eliminated. In order to select the papers that will be included in the scoping review, the recorded papers will be screened. The screening of the identified references will be performed at the level of the title, abstract and the full text. Two independent researchers will work on the pre-selection and selection of the studies and a third researcher will act as a mediator for agreement of the selection. The titles, abstracts and texts should mention the multidisciplinary management of obesity through digital health, based on nutrition education, promotion of regular physical activity and/or psychological support. ++The following selection criteria will be applied to define the eligibility of a study: Population: Human 6-64 years, having overweight or obesity, no pregnant. Intervention/Exposure: Digital technologies to manage obesity including overweight, based on a multidisciplinary approach including nutrition education, promotion of physical activity and/or psychological support. - Study Design: Observational studies (cross sectional studies, case-control, and cohorts) or interventional studies (randomized controlled trials and non-randomized controlled trials). A consistency check will be performed on a random sample of the selected references in order to assess the inter reviewer agreement, following the application of the selection criteria. -. Data extraction: The following information will be extracted from the selected papers: +Study information ++ Specific Objective of the study (feasibility, efficacy or efficiency) ++ Study design ++ Study location and country (school, workplace…) ++ Study duration (weeks) ++ Study / Weight management program's name ++ Type of digital health technology used (internet-based weight loss program, mobile application…) ++ Name of the digital health technology used (MyFitnessPal, Lose it!....) ++ Target population: Adults / Children / Parent-child dyad (yes, no) ++ Sample size ++ Gender (N, %) ++ Age (minimum, maximum) ++ Dropout (N, %) ++ Interventions: Nutritional education, physical activity, psychological support without and with digital health. + Study outcomes ++ Feasibility, efficacy and/or efficiency ++ Anthropometric, clinical, biological and nutrition-physical activity-psychology related outcomes. - Data presentation: The presentation of the data and the results will include the description of the study selection process through a flow diagram based on the PRISMA for scoping review checklist, as well as a bibliographic reference list for each database after elimination of the duplicates, the results of the consistency check. The main findings will be presented in tables and supplementary material. - Co-authors contributions: HS conceptualized the study and coordinated the review. AB and SSFDC performed the systematic search. SSFDC, GRM and B Leners performed the papers selection and data extraction. HS acted as a mediator for agreement of the studies selection and data extraction. SS advised the team on the scoping review process. SSFDC and HS drafted the manuscript. AB, GF, SS, B Lefebvre and TB provided further input to the manuscript. All authors critically revised the manuscript for important intellectual content, and approved the final version. - Acknowledgement: We acknowledge Coralie Dessenne, Documentation Officer at the Luxembourg Institute of Health, for her support, especially her advice advising on the literature search. - References: 1. Bischoff SC, Damms-Machado A, Betz C, Herpertz S, Legenbauer T, Low T, et al. Multicenter evaluation of an interdisciplinary 52-week weight loss program for obesity with regard to body weight, comorbidities and quality of life--a prospective study. Int J Obes (Lond). 2012; 36: 614-24. 2. Yumuk V, Tsigos C, Fried M, Schindler K, Busetto L, Micic D, et al. European Guidelines for Obesity Management in Adults. Obesity facts. 2015; 8: 402-24. 3. Yumuk V, Fruhbeck G, Oppert JM, Woodward E, Toplak H. An EASO position statement on multidisciplinary obesity management in adults. Obesity facts. 2014; 7: 96-101. 4. Ross MM, Kolbash S, Cohen GM, Skelton JA. Multidisciplinary treatment of pediatric obesity: nutrition evaluation and management. Nutr Clin Pract. 2010; 25: 327-34. 5. World Health Organisation. WHO Guideline: recommendations on digital interventions for health system strengthening. 2019. 6. Castelnuovo G, Simpson S. Ebesity - e-health for obesity - new technologies for the treatment of obesity in clinical psychology and medicine. Clin Pract Epidemiol Ment Health. 2011; 7: 5-8

Potential health effects of brewers’ spent grain as a functional food ingredient assessed by markers of oxidative stress and inflammation following gastro-intestinal digestion and in a cell model of the small intestine

Brewery spent grain increased dietary fiber when incorporated into bread, together with total phenolics and antioxidant capacity. This was retained after gastro-intestinal digestion. 150 g of such a bread can supply the recommended daily 25 g of fiber.</jats:p

Multidisciplinary management of obesity through digital-health: a scoping review.

A scoping review will be conducted in order to summarise the available evidence on digital health and multidisciplinary management of obesity including overweight. Studies will be selected if the obesity management is based on nutrition education, promotion of regular physical activity and/or psychological support through digital health. The PRISMA-ScR checklist (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Review) will be followed. - Hypotheses and objectives Obesity is a multifactorial disease. Multidisciplinary approaches based on nutrition education, promotion of regular physical activity and/or psychological support provide an optimal management of obesity (1-4). As digital health enables people to manage their own health, digital health technologies might sustainably help to take charge of obesity (5, 6). - The objective of the scoping review is to summarise the available evidence on multidisciplinary management of obesity through digital health, based on nutritional, exercise and/or psychological support. - Design Plan: + Study type: Scoping review. + Study design: Scoping review based on a systematic search of evidence. The evidence will include observational (i.e. cross-sectional, case-control studies and cohorts) and experimental (i.e. randomised controlled trials or non-randomised trials) studies. - Sampling Plan: + Existing Data: The present study corresponds to the first research conducted by our group in this domain. + Explanation of existing data: Understanding on the existing data has been limited to exploratory non-systematic searches of reviews and studies using PubMed. + Data collection procedures: ++Eligibility criteria: Studies published in English since January 1st 2000 will be considered. Studies will be selected if they consider the management of obesity as a disease through digital health in humans. Eligible studies will have information on the multidisciplinary management of obesity, including overweight, through nutrition education, physical activity promotion and/or psychological support through digital health technologies. Original research will be eligible. Brief reports, reviews and commentaries will be considered as a potential source of references not found in our systematic search. The age range of inclusion will be between 6 and 64 years old: children (6-12 years), adolescents (13-18 years), adults (19-44 years) and people at middle age (45-64 years) having overweight or obesity. ++Exclusion criteria: Children and adults with normal weight (without overweight or obesity), Children &lt; 6 years, Elderly people (≥ 65 years), Studies targeting the management of other chronic diseases than obesity as primary outcome (e.g. cardiovascular disease, diabetes, cancer, hypertension…). In these studies, obesity is not considered as a disease, but as a risk factor of the other chronic diseases, Pregnancy, Articles published languages other than English, “Grey” literature (reports, doctoral theses, conference contributions, book chapters, editorials), unless they will be used to identify potential references. ++Systematic search: 1. An exhaustive systematic search of the literature will be performed through the following selected databases: PubMed covering all records from Medline, as well as in-processing publications, Scopus covering all records from PsycINFO and Web of Science, in addition to Medline records. If needed we will contact colleagues working on the topic of interest to ask to them for potential relevant material. 2. Joanna Briggs Manual: The scoping review will be performed according to the Joanna Briggs Manual: 2.1. Identification of key words An initial limited search in 20 previously published papers will be performed. This will enable us to identify the main keywords and synonyms associated with the topic. These keywords will be extracted from the title, abstract and the main text of the selected articles. A snowball search will be performed, based on the references cited in the selected papers. The 20 most significant studies will be selected from the snowball search. A MeSH (Medical Subject Headings) terms search will also be conducted. 2.2. - Execution of systematic search: The systematic final search will be conducted, in the selected databases, based on the combination of the selected keywords. The search strategy will have the following structure: “keywords for obesity” AND “keywords for digital health” AND “keywords for nutritional education OR promotion of physical activity OR psychological support”. The full electronic search strategy will be presented in the appendix of the final manuscript. ++Data charting process: The open access online software CADIMA (JKI—Julius Kühn-Institut, vers. 2.1.3 - Feb 2020) will be used to conduct the systematic search. +++ Papers selection: The literature search will be uploaded from the PubMed and Scopus databases into the software CADIMA as a bibliographic citation file that will be registered in RIS (Research Information Systems) format. The search results will then be combined. The duplicated studies will be detected and eliminated. In order to select the papers that will be included in the scoping review, the recorded papers will be screened. The screening of the identified references will be performed at the level of the title, abstract and the full text. Two independent researchers will work on the pre-selection and selection of the studies and a third researcher will act as a mediator for agreement of the selection. The titles, abstracts and texts should mention the multidisciplinary management of obesity through digital health, based on nutrition education, promotion of regular physical activity and/or psychological support. The following selection criteria will be applied to define the eligibility of a study: ++++ Population: Human 6-64 years, having overweight or obesity, no pregnant. ++++ Intervention/Exposure: Digital technologies to manage obesity including overweight, based on a multidisciplinary approach including nutrition education, promotion of physical activity and/or psychological support. ++++ Study Design: Observational studies (cross sectional studies, case-control, and cohorts) or interventional studies (randomized controlled trials and non-randomized controlled trials). A consistency check will be performed on a random sample of the selected references in order to assess the inter reviewer agreement, following the application of the selection criteria. +++ Data extraction: The following information will be extracted from the selected papers: ++++Study information: Specific Objective of the study (feasibility, efficacy or efficiency) Study design Study location and country (school, workplace…) Study duration (weeks) Study / Weight management program's name Type of digital health technology used (internet-based weight loss program, mobile application…) Name of the digital health technology used (MyFitnessPal, Lose it!....) ++++Target population: Adults / Children / Parent-child dyad (yes, no) Sample size Gender (N, %) Age (minimum, maximum) Dropout (N, %) ++++ Approaches: Nutritional intervention / Digital health-Nutritional intervention / Physical activity intervention / Digital health- Physical activity intervention / Psychological support intervention / Digital health- Psychological support intervention / Control Group / Dropout. - Study outcomes: + Feasibility, efficacy and/or efficiency + Anthropometric, biological, clinical, nutrition-physical activity and psychological related outcomes. - Data presentation: The presentation of the data and the results will include the description of the study selection process through a flow diagram based on the PRISMA for scoping review checklist, as well as a bibliographic reference list for each database after elimination of the duplicates, the results of the consistency check. The main findings will be presented in tables and supplementary material. - Co-authors contributions: HS conceptualized the study and coordinated the review. AB and SSFDC performed the systematic search. SSFDC, GRM and B Leners performed the papers selection and data extraction. HS acted as a mediator for agreement of the studies selection and data extraction. SS advised the team on the scoping review process. SSFDC and HS drafted the manuscript. AB, GF, SS, B Lefebvre and TB provided further input to the manuscript. All authors critically revised the manuscript for important intellectual content, and approved the final version. - Acknowledgement: We acknowledge Coralie Dessenne, Documentation Officer at the Luxembourg Institute of Health, for her support, especially her advice advising on the literature search. - References: 1. Bischoff SC, Damms-Machado A, Betz C, Herpertz S, Legenbauer T, Low T, et al. Multicenter evaluation of an interdisciplinary 52-week weight loss program for obesity with regard to body weight, comorbidities and quality of life--a prospective study. Int J Obes (Lond). 2012; 36: 614-24. 2. Yumuk V, Tsigos C, Fried M, Schindler K, Busetto L, Micic D, et al. European Guidelines for Obesity Management in Adults. Obesity facts. 2015; 8: 402-24. 3. Yumuk V, Fruhbeck G, Oppert JM, Woodward E, Toplak H. An EASO position statement on multidisciplinary obesity management in adults. Obesity facts. 2014; 7: 96-101. 4. Ross MM, Kolbash S, Cohen GM, Skelton JA. Multidisciplinary treatment of pediatric obesity: nutrition evaluation and management. Nutr Clin Pract. 2010; 25: 327-34. 5. World Health Organisation. WHO Guideline: recommendations on digital interventions for health system strengthening. 2019. 6. Castelnuovo G, Simpson S. Ebesity - e-health for obesity - new technologies for the treatment of obesity in clinical psychology and medicine. Clin Pract Epidemiol Ment Health. 2011; 7: 5-8

Determination of genes and microRNAs involved in the resistance to fludarabine in vivo in chronic lymphocytic leukemia

Background: Chronic lymphocytic leukemia (CLL) cells are often affected by genomic aberrations targeting key regulatory genes. Although fludarabine is the standard first line therapy to treat CLL, only few data are available about the resistance of B cells to this purine nucleoside analog in vivo. Here we sought to increase our understanding of fludarabine action and describe the mechanisms leading to resistance in vivo. We performed an analysis of genomic aberrations, gene expression profiles, and microRNAs expression in CLL blood B lymphocytes isolated during the course of patients' treatment with fludarabine. Results: In sensitive patients, the differentially expressed genes we identified were mainly involved in p53 signaling, DNA damage response, cell cycle and cell death. In resistant patients, uncommon genomic abnormalities were observed and the resistance toward fludarabine could be characterized based on the expression profiles of genes implicated in lymphocyte proliferation, DNA repair, and cell growth and survival. Of particular interest in some patients was the amplification of MYC (8q) observed both at the gene and transcript levels, together with alterations of myc-transcriptional targets, including genes and miRNAs involved in the regulation of cell cycle and proliferation. Differential expression of the sulfatase SULF2 and of miR-29a, -181a, and -221 was also observed between resistant and sensitive patients before treatment. These observations were further confirmed on a validation cohort of CLL patients treated with fludarabine in vitro. Conclusion: In the present study we identified genes and miRNAs that may predict clinical resistance of CLL to fludarabine, and describe an interesting oncogenic mechanism in CLL patients resistant to fludarabine by which the complete MYC-specific regulatory network was altered (DNA and RNA levels, and transcriptional targets). These results should prove useful for understanding and overcoming refractoriness to fludarabine and also for predicting the clinical outcome of CLL patients before or early during their treatment