124 results on '"Matar, C."'
Search Results
2. Numerical Investigation of the Transonic Non-ideal Gas Flow Around a Circular Cylinder at High Reynolds Number
- Author
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Matar, C., primary, Cinnella, P., additional, Gloerfelt, X., additional, Sundermeier, S., additional, Hake, L., additional, and Wiesche, S. aus der, additional
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- 2023
- Full Text
- View/download PDF
3. Rezidivierendes DMEK-Versagen
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Matar, C., Seitz, B., and Daas, L.
- Published
- 2021
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4. Reliabilität der Hornhauttomographie nach Implantation von intrakornealen Ringsegmenten bei Keratokonus
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Matar, C., Daas, L., Suffo, S., Langenbucher, A., Seitz, B., and Eppig, T.
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- 2020
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5. CFD-supported data reduction of hot-wire anemometry signals for compressible organic vapor flows
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Hake, L, primary, Sundermeier, S, additional, Wiesche, S aus der, additional, Bienner, A., additional, Gloerfelt, X, additional, Matar, C, additional, and Cinnella, P, additional
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- 2023
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6. Bioactive Peptides from Fermented Foods: Their Role in the Immune System
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Matar, C., Goulet, J., Bernier, R. L., Brochu, E., Fuller, R., editor, and Perdigon, G., editor
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- 2000
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7. Does EBV alter the pathogenesis of malaria?
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MATAR, C. G., JACOBS, N. T., SPECK, S. H., LAMB, T. J., and MOORMANN, A. M.
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- 2015
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8. Prophylactic anticoagulants for people hospitalized with COVID-19: systematic review
- Author
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Flumignan, R L, primary, Tinôco, J D de Sá, additional, Pascoal, P I, additional, Areias, L L, additional, Cossi, M S, additional, Fernandes, M I, additional, Costa, I K, additional, Souza, L, additional, Matar, C F, additional, Tendal, B, additional, Trevisani, V F, additional, Atallah, Á N, additional, and Nakano, L C, additional
- Published
- 2021
- Full Text
- View/download PDF
9. Rezidivierendes DMEK-Versagen
- Author
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Matar, C, Seitz, B, Daas, L, Matar, C, Seitz, B, and Daas, L
- Published
- 2020
10. Study of cytokines involved in the prevention of a murine experimental breast cancer by kefir
- Author
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de Moreno de LeBlanc, A., Matar, C., Farnworth, E., and Perdigon, G.
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- 2006
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- View/download PDF
11. Rezidivierendes DMEK-Versagen
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Matar, C., primary, Seitz, B., additional, and Daas, L., additional
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- 2020
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12. Antiobesity and antidiabetic effects of biotransformed blueberry juice in KKAy mice
- Author
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Vuong, T, Benhaddou-Andaloussi, A, Brault, A, Harbilas, D, Martineau, LC, Vallerand, D, Ramassamy, C, Matar, C, and Haddad, PS
- Published
- 2009
13. Oral manifestations of inflammatory bowel disease
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Mortada, I., LEONE, Angelo, Gerges Geagea, A., Mortada, R., Matar, C., RIZZO, Manfredi, Hajj Hussein, I., Massaad Massade, L., Gerges, Alice, Mortada, I., Leone, A., Gerges Geagea, A., Mortada, R., Matar, C., Rizzo, M., Hajj Hussein, I., Massaad-Massade, L., and Jurjus, A.
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Mouth ,Animals ,Humans ,Oral manifastation, inflammation, bowel disease ,Stomatitis, Aphthous ,Inflammatory Bowel Diseases ,Gingivitis - Abstract
Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, have important extraintestinal manifestations, notably in the oral cavity. These oral manifestations can constitute important clinical clues in the diagnosis and management of IBD, and include changes at the immune and bacterial levels. Aphthous ulcers, pyostomatitis vegetans, cobblestoning and gingivitis are important oral findings frequently observed in IBD patients. Their presentations vary considerably and might be well diagnosed and distinguished from other oral lesions. Infections, drug side effects, deficiencies in some nutrients and many other diseases involved with oral manifestations should also be taken into account. This article discusses the most recent findings on the oral manifestations of IBD with a focus on bacterial modulations and immune changes. It also includes an overview on options for management of the oral lesions of IBD.
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- 2017
14. Vergleich zwischen Gastamponade mit 20% Schwefelhexafluorid und Lufttamponade bei DMEK-Patienten
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Matar, C., Daas, L., Milioti, G., Suffo, S., and Seitz, B.
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Ziel: Vergleich der Re-Bubbling-Rate und der funktionellen Ergebnisse zwischen Luft- und 20% Schwefelhexafluorid (SF6) Gastamponnade bei der Descemet Membrane Endothelial Keratoplasty (DMEK). Patienten und Methoden: Es wurden retrospektiv 88 Augen von 86 Patienten mit Fuchs Dystrophie, pseudophaker[zum vollständigen Text gelangen Sie über die oben angegebene URL], 91. Versammlung des Vereins Rhein-Mainischer Augenärzte
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- 2018
15. Vergleich zwischen Gastamponade mit 20% Schwefelhexafluorid und Lufttamponade bei DMEK-Patienten
- Author
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Matar, C, Daas, L, Milioti, G, Suffo, S, Seitz, B, Matar, C, Daas, L, Milioti, G, Suffo, S, and Seitz, B
- Published
- 2018
16. Role of probiotics and prebiotics in immunomodulation
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Yahfoufi, N, primary, Mallet, JF, additional, Graham, E, additional, and Matar, C, additional
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- 2018
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17. Remote-site stimulation and duration of the immune response by kefir
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Vinderola, Celso Gabriel, Duarte, J., Thangavel, D., Perdigon, Gabriela del Valle, Farnworth, E., and Matar, C.
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Alimentos y Bebidas ,purl.org/becyt/ford/2 [https] ,Otras Ingenierías y Tecnologías ,Remote-site ,INGENIERÍAS Y TECNOLOGÍAS ,kefir ,immune response ,purl.org/becyt/ford/2.11 [https] - Abstract
Kefir is a fermented milk (drink) produced by the action of lactic acid bacteria, yeasts and acetic acid bacteria. We recently reported a comparative study on the effect of kefir containing viable or non-viable bacteria by studying their modulatory activity on the intestinal immune response. A functional dose was established in a murine model and the pattern of regulatory and pro-inflammatory cytokines induced was also studied. The existence of a common mucosal immune system implies that the immune cells stimulated in one mucosal tissue can spread and relocate through various mucosal sites. The aim of this work was to determine the effect of an oral administration of kefir on the duration of the intestinal mucosa immune response and the modulatory activity in distal mucosal sites, specifically in the peritoneal and pulmonary acrophages and in the bronchial tissue. BALB/c mice were fed with kefir or pasteurized kefir at doses previously determined as functional for intestinal mucosa immunomodulation. Kefir feeding was stopped and the number of IgA, IgG, IL-4, IL-6, IL-10, IIFNg and TNFa producing cells was determined in the lamina propria of small intestine immediately, and after 2 and 7 days of kefir withdrawal. IgAproducing cells were also measured in the bronchial tissue of lungs immediately and 2 and 7 days after kefir withdrawal. Phagocytic activity of peritoneal and pulmonary macrophages was also determined. The oral administration of kefir or pasteurized kefir increased the number of IgA+ cells not only in the gut lamina propria, but also in the bronchial tissue, supporting the concept of local antibody secretion after remote-site stimulation in the intestinal tract. Both peritoneal and pulmonary macrophages were activated by kefir or pasteurized kefir feeding. Peritoneal macrophages were stimulated faster than pulmonary macrophages (for kefir). The enhanced phagocytic activity achieved by kefir or pasteurized kefir lasted longer for the peritoneal than for the pulmonary macrophages. Due to the increased bronchial IgA and phagocytic activity of pulmonary macrophages after kefir feeding observed in this study, the oral administration of kefir could act as a natural adjuvant for enhancing the specific immune response against respiratory pathogens. The parameters studied returned to control values within a week of cessation of kefir administration. This would suggest that there is a low risk of overstimulating the gut mucosal immune system during periodic consumption of viable kefir. Fil: Vinderola, Celso Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina Fil: Duarte, J.. University of Moncton; Canadá Fil: Thangavel, D.. University of Moncton; Canadá Fil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán; Argentina Fil: Farnworth, E.. 4Agriculture and Agri-Food Canada; Canadá Fil: Matar, C.. University of Moncton; Canadá
- Published
- 2005
18. GSH monoethyl ester rescues mitochondrial defects in cystic fibrosis models
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Kelly-Aubert, M., primary, Trudel, S., additional, Fritsch, J., additional, Nguyen-Khoa, T., additional, Baudouin-Legros, M., additional, Moriceau, S., additional, Jeanson, L., additional, Djouadi, F., additional, Matar, C., additional, Conti, M., additional, Ollero, M., additional, Brouillard, F., additional, and Edelman, A., additional
- Published
- 2011
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19. ‘Desperate house genes’: the dramatic example of hypoxia
- Author
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Caradec, J, primary, Sirab, N, additional, Keumeugni, C, additional, Moutereau, S, additional, Chimingqi, M, additional, Matar, C, additional, Revaud, D, additional, Bah, M, additional, Manivet, P, additional, Conti, M, additional, and Loric, S, additional
- Published
- 2010
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20. Mucosal immunomodulation by the non-bacterial fraction of milk fermented by Lactobacillus helveticus R389
- Author
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VINDEROLA, G, primary, MATAR, C, additional, PALACIOS, J, additional, and PERDIGON, G, additional
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- 2007
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21. Study of Immune Cells Involved in the Antitumor Effect of Kefir in a Murine Breast Cancer Model
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de Moreno de LeBlanc, A., primary, Matar, C., additional, Farnworth, E., additional, and Perdigón, G., additional
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- 2007
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22. Distal Mucosal Site Stimulation by Kefir and Duration of the Immune Response
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Vinderola, C. G., primary, Duarte, J., additional, Thangavel, D., additional, Perdigon, G., additional, Farnworth, E., additional, and Matar, C., additional
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- 2005
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23. On zero clock skew hold time failure in scan test.
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Xiaonan Zhang, Xiaoliang Bai, Laisne, M., and Matar, C.
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- 2008
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24. Immunomodulating Effects of Peptidic Fractions Issued from Milk Fermented with Lactobacillus helveticus
- Author
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LeBlanc, J.G., primary, Matar, C., additional, Valdéz, J.C., additional, LeBlanc, J., additional, and Perdigon, G., additional
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- 2002
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25. Antiobesity and antidiabetic effects of biotransformed blueberry juice in KKAy mice.
- Author
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Vuong, T., Benhaddou-Andaloussi, A., Brault, A., Harbilas, D., Martineau, L. C., Vallerand, D., Ramassamy, C., Matar, C., and Haddad, P. S.
- Subjects
LABORATORY mice ,BLUEBERRIES ,BODY weight ,MUSCLE cells ,OBESITY - Abstract
Aim:Biotransformation of blueberry juice by the Serratia vaccinii bacterium gave rise to adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and glucose uptake in muscle cells and adipocytes, but inhibited adipogenesis. This study investigated the antiobesity and antidiabetic potential of biotransformed blueberry juice (BJ) in KKA
y mice, rodent model of leptin resistance.Methods:BJ was incorporated in drinking water of KKAy mice. Parameters of body weight, food intake, plasma glucose, insulin, leptin, and adiponectin were measured. Before and after therapy, animals were subjected to an oral glucose tolerance test. At the end of treatment, liver, muscle, kidney, epididymal fat pad, abdominal fat pad, and dorsal fat pad were collected and weighed.Results:Incorporating BJ in drinking water protected young KKAy mice from hyperphagia and significantly reduced their weight gain. Moreover, BJ protected young KKAy mice against the development of glucose intolerance and diabetes mellitus. Chronic BJ administration in obese and diabetic KKAy mice reduced food intake and body weight. This effect could not fully explain the associated antidiabetic effect because BJ-treated mice still showed lower blood glucose level when compared with pair-fed controls. The adipokines pathway also seems to be involved because BJ significantly increased adiponectin levels in obese mice.Conclusions:This study shows that BJ decreases hyperglycemia in diabetic mice, at least in part by reversing adiponectin levels. BJ also protects young pre-diabetic mice from developing obesity and diabetes. Thus, BJ may represent a novel complementary therapy and a source of novel therapeutic agents against diabetes mellitus. [ABSTRACT FROM AUTHOR]- Published
- 2009
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26. -Casomorphin 4 from Milk Fermented by a Mutant of Lactobacillus helveticus
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Matar, C. and Goulet, J.
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- 1996
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27. Pandemiebedingtes Verkaufsverbot von Feuerwerkskörpern in Deutschland führt zu einer deutlichen Abnahme der Augenverletzungen
- Author
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Gabel-Pfisterer, Ameli, Böhringer, Daniel, Agostini, Hansjürgen, Feuerwerks-Verletzungen-Studiengruppe, Botros, Y., Krieb, A., Emmerich, K.-H., Grajewski, L., Krause, L., Hoa, D. Q., Yilmaz, S., Jabur, A., Rüdiger, K., Boeker, T., Rashitova, D., Eberlein, G., Lehmann, F., Sachs, H., Matthee, E., Pillunat, L., Juergens, L., Kaya, S., Guthoff, R., Steindorf, F., Korbmacher, J., Geerling, G., Märtz, J., Widder, R., Rössler, G., Iseed, A., Doulgkeridis, J., Erhard, J., Tomalla, M., von Jagow, B., Filev, F., Schill, S., Kotiasvili, T., Kojetinski, C., Flach, A., Zollfrank, C., Lieder, A., Blum, M., Tourtas, T., Knorr, H., Kruse, F., Freimuth, M., Dalbah, S., Sokolenko, E., Mueller, A., Rating, P., Kiefer, T., Book, B., Westerkemper, H., Böhm, M., Bornfeld, N., Bechrakis, N., Schultheiss, M., Scheider, A., Pawlowczicz, K., Hagenbusch, J., Müller, M., Kohnen, T., Ahdab, K., Eckert, T., Eckardt, C., Wisniewska, M., Just, A., Laich, Y., Stifter, J., Avar, M., Gritzka, M., Jehle, V., Reinhard, T., Rab, S., Seewald, J., Mais, C., Basiakos, S., Osman, B., Xanthopoulou, E., Friedburg, B., Graef, M. H., Dempe, C., Lorenz, B., Just, U., Schrecker, J., Klemming, J., Drüke, D., Bemmer, L., Weiß, S., Take, P., Nguyen-Höhl, A., Oterendorp, C., Al-Ashi, N., Feltgen, N., Hoerauf, H., Prusiecki, I., Elle, J., Gundel, B., Bender, M. C., Menges, A., Tost, F., Stahl, A., Wienrich, R., Breuß, H., Huth, A., Viestenz, A., Ueberschaar, J., Daehn, T., Brooks, U., Schindler, P., Bigdon, E., Bertram, P., Skevas, C., Kromer, R., Kuchenbecker, J., Casagrande, M., Grohmann, C., Mehlan, J., Spitzer, M., Schargus, M., Eddy, M., Schumacher, S., Keserü, M., Scheler, A., Foerster, M. H., Stemplewitz, B., Schaudig, U., Herden, J., Haar, M., Tode, B., Junker, B., Abou Mouli, W., Volkmann, I., Framme, C., Scheuerle, A., Seibel, I., Auerbach, M., Beisse, C., Rohrschneider, K., Auffahrt, G., Mala, N., Rosenthal, A., Hesse, L., Daas, L., Flockerzie, E., Suffo, S., Böker, A., Seitz, B., Chrisoglou, N., Wietstock, G., Augsten, R., Meller, D., Althauspetervari, I., Rudolph, O., Floeter, C., Beutner, A., Effert, R., Greve, D., Mayer, M., Vanselow, K., Lieb, W., Kandzia, C., Purtskhvanidze, K., Ehlken, C., Roider, J., Hueber, A., Cursiefen, K., Edelmann, C., Lenglinger, M., Schrage, N., Kroeger, M., Viehweg, N., Meier, P., Unterlauft, J. D., Wiedemann, P., Rehak, M., Ziemssen, F., Rommel, F., Sonntag, S., Müller, B., Prasuhn, M., Pawlik, V., Kakkassery, V., Ranjbar, M., Mohi, A., Grisanti, S., Bastron, I., Dindin-Sarac, S., Kaskel-Paul, S., Rawohl, J., Schönfeld, S., Hattenbach, L., Stoffelns, B., Schuster, A., Pfeiffer, N., Besgen, V., Schröder, F., Schulze, S., Weber, N., Sekundo, W., Schuart, C., Renieri, G., Weigel, M., Thieme, H., Hagenau, F., Wolf, A., Vounotrypidis, E., Priglinger, S., Penkava, J., Klein, J., Bechstein, L., Joussen, A., Maier, M., Lohmann, C., Haritoglu, C., Alten, F., Eter, N., Brinkmann, C., Alshikh, F., Klishko, V., Holland, U., Medra, A., Kolarov, D., Weber, A., Höh, H., Pielen, A., Zschockelt, T., Luciani, F., Schmidbauer, J., Horn, P., Kodomskoi, L., Kuempel, H., Schwarz, P., Rivera Gomez, C., Plantzas, K., Weiss, M., Hille, K., Esper, G., Mazko, K., Kolbeck, L., Malek, S., Kupper, P., Grafmueller, S., Puk, C., Schrader, S., Darawsha, R., Bellios, N., Wulff, V., Ghaffary, A., Ghoreishi, A., Höhn, F., Napholz, A., Tandogan, T., Schmidt, L., Berthold, A., Ilski, P., Trossowski, C., Zühlsdorff-Utke, M., Liekfeld, A., Winter, I., Böhm, A., Blecha, C., Barth, T., Helbig, H., Rusch, W., Wirbelauer, C., Noerenberg, A., Juenemann, A., Fuchsluger, T. A., Matar, C., Zuche, M., Roehrig, S., Decker, A., Kühn, M., Ladewig, M., Schmidt-Wetter, J., Hofmayer, H., Machulla, R., Boateng, A.-F., Dias Blak, M., Krawczyk, S., Lenhard, K., Lackner, B., Gekeler, F., Mamacek, D., Wocker, L., Holzschuh, I., Wachtlin, J., Boden, K. T., Szurmann, P., Faul, D., May-Endres, K., Press, U., Luttke, J., Wolfram, L., Reichel, F., Seitz, I., Bartz-Schmidt, U., Speidel, A., Cordes, J., Raber, F., Mikielewicz, M., Kammerer, J., Kupferschmid, S., Buchwald, H., Werner, J., Meyer, J. F., Kampmeier, J., Dithmar, S., Fischer, G., Pruefke, C., Bula, A., Krauß, P., Strzalkowski, P., Hillenkamp, J., Macher, T., Kuerten, D., Palka, K., Niemeyer, M., Walla, T., Pham, D., Aisenbrey, S., Rieck, P., Verbeck, J., Tatsiou, A., Walch, A., Burk, R., Fuest, M., Schnober, G., Elling, M., Schultz, T., Tsiampalis, N., Rehmann, J., Sliwowska, U., Schojai, M., Schulze, K., Kamguia, N., Wirtz, C., Walter, P., Dick, B., Bourauel, L., Schützeichel, F. M., Völcker, D., Wintergerst, M., Pfau, M., Melzer, C., Hoegen, D., Bosch, F., Andresen, J. C., Wanjek-Meyer, K., Krohne, T., Holz, F. G., Fries, U., Koch, M., Kwasnicki, A., Kathke, M., Noske, W., Sturm, A., Chankiewitz, E., Monastoriotis, S., Kohen, L., Kemper, O., Hübner, T., Feldmann, M., Morsek, J., Rainer, O., Bartsch, H., Ewald, K., Brandter, S., Cil, M. U., Hartmann, K., Siegmund, T., Bohlen, A., Mohr, A., Wienigk, A., Hecker, J., Smetana, P., Furashova, O., Engelmann, K., Shtaya, M., and Müller, A.-K.
- Abstract
Die Ophthalmologie 119(12), 1257-1266 (2022). doi:10.1007/s00347-022-01778-1, Published by Springer Medizin, Berlin ; Heidelberg
- Published
- 2022
28. Recommendations for pregnancy in Fanconi anemia
- Author
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Ali T. Taher, Achille Iolascon, Roberta Russo, Charbel F Matar, Rayan Bou-Fakhredin, Immacolata Andolfo, Matar, C. F., Bou-Fakhredin, R., Russo, R., Andolfo, I., Iolascon, A., and Taher, A. T.
- Subjects
0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Bone marrow transplantation ,bone marrow transplantation ,Clinical Biochemistry ,fetal outcome ,03 medical and health sciences ,0302 clinical medicine ,Fanconi anemia ,Pregnancy ,hemic and lymphatic diseases ,Drug Discovery ,medicine ,Humans ,Pharmacology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Bone marrow failure ,medicine.disease ,maternal outcome ,030104 developmental biology ,030220 oncology & carcinogenesis ,Fetal outcome ,Female ,Congenital disease ,delivery ,business - Abstract
Introduction: Fanconi anemia (FA) is a rare congenital disease that belongs to the family of congenital trilinear bone marrow failure. Most FA patients will suffer bone marrow failure and the main treatment relies on supportive measures or more recently on the use of hematopoietic stem cell transplant. The improvements seen in the management of FA has led women to reach childbearing age and have successful pregnancies. However, these pregnancies are associated with increased complications such as preterm delivery, cesarean delivery, eclampsia and others. Areas covered: This review highlights on the outcome of pregnancies in FA patients reported in the literature along with practical recommendations. Expert opinion: Multidisciplinary efforts are required to optimize the management of pregnancy in FA patients. Moreover, the development of a set of recommendations to optimize the treatment is highly necessary.
- Published
- 2021
29. Edodes Cultured Extract Regulates Immune Stress During Puberty and Modulates MicroRNAs Involved in Mammary Gland Development and Breast Cancer Suppression.
- Author
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Yasavoli-Sharahi H, Shahbazi R, Alsadi N, Robichaud S, Kambli DB, Izadpanah A, Mohsenifar Z, and Matar C
- Subjects
- Animals, Female, Mice, Cytokines metabolism, Puberty, MicroRNAs genetics, Mammary Glands, Animal metabolism, Mammary Glands, Animal immunology, Mammary Glands, Animal drug effects, Breast Neoplasms immunology, Breast Neoplasms metabolism, Mice, Inbred BALB C, Lipopolysaccharides
- Abstract
Background: Immune stressors, such as lipopolysaccharides (LPS), profoundly affect microbiota balance, leading to gut dysbiosis. This imbalance disrupts the metabolic phenotype and structural integrity of the gut, increasing intestinal permeability. During puberty, a critical surge in estrogen levels is crucial for mammary gland development. However, inflammation originating from the gut in this period may interfere with this development, potentially heightening breast cancer risk later. The long-term effects of pubertal inflammation on mammary development and breast cancer risk are underexplored. Such episodes can dysregulate cytokine levels and microRNA expression, altering mammary cell gene expression, and predisposing them to tumorigenesis., Methods: This study hypothesizes that prebiotics, specifically Lentinula edodes Cultured Extract (AHCC), can counteract LPS's adverse effects. Using BALB/c mice, an acute LPS dose was administered at puberty, and breast cancer predisposition was assessed at 13 weeks. Cytokine and tumor-related microRNA levels, tumor development, and cancer stem cells were explored through immunoassays and qRT-PCR., Results: Results show that LPS induces lasting effects on cytokine and microRNA expression in mammary glands and tumors. AHCC modulates cytokine expression, including IL-1β, IL-17A/F, and IL-23, and mitigates LPS-induced IL-6 in mammary glands. It also regulates microRNA expression linked to tumor progression and suppression, particularly counteracting the upregulation of oncogenic miR-21, miR-92, and miR-155. Although AHCC slightly alters some tumor-suppressive microRNAs, these changes are modest, highlighting a complex regulatory role that warrants further study., Conclusion: These findings underscore the potential of dietary interventions like AHCC to mitigate pubertal LPS-induced inflammation on mammary gland development and tumor formation, suggesting a preventive strategy against breast cancer., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2024
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30. Role of a Polyphenol-Enriched Blueberry Preparation on Inhibition of Melanoma Cancer Stem Cells and Modulation of MicroRNAs.
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Alsadi N, Yahfoufi N, Nessim C, and Matar C
- Abstract
Melanoma is a type of skin cancer known for its high mortality rate. Cancer stem cells (CSCs) are a subpopulation of cancer cells that significantly contribute to tumour recurrence and differentiation. Epigenetic-specific changes involving miRNAs maintain CSCs. Plant polyphenols have been reported to be involved in cancer chemoprevention and chemotherapy, with miRNAs being the novel effectors in their biological activities. A polyphenol-enriched blueberry preparation (PEBP) derived from fermented blueberries has demonstrated promising chemopreventative properties on breast cancer stem cells by influencing inflammatory pathways and miRNAs. In our current investigation, we seek to unveil the impact of PEBP on inhibiting melanoma development and to elucidate the underlying mechanisms. Our study employs various human cell lines, including an ex vivo cell line derived from a patient's metastatic tumour. We found that it elevates miR-200c, increasing E-cadherin expression and inhibiting miR-210-3p through NF-κB signalling, impacting Epithelial-to-Mesenchymal Transition (EMT), a critical process in cancer progression. PEBP increases the SOCS1 expression, potentially contributing to miR-210-3p inhibition. Experiments involving miRNA manipulation confirm their functional roles. The study suggests that PEBP's anti-inflammatory effects involve regulating miR-200c and miR-210 expression and their targets in EMT-related pathways. The overall aim is to provide evidence-based supportive care and preclinical evaluation of PEBP, offering a promising strategy for skin cancer chemoprevention.
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- 2024
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31. Protective Mechanisms of Polyphenol-Enriched Blueberry Preparation in Preventing Inflammation in the Skin against UVB-Induced Damage in an Animal Model.
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Alsadi N, Yasavoli-Sharahi H, Mueller R, Cuenin C, Chung F, Herceg Z, and Matar C
- Abstract
UVB significantly impacts the occurrence of cutaneous disorders, ranging from inflammatory to neoplastic diseases. Polyphenols derived from plants have been found to exhibit photoprotective effects against various factors that contribute to skin cancer. During the fermentation of the polyphenol-enriched blueberry preparation (PEBP), small oligomers of polyphenols were released, thus enhancing their photoprotective effects. This study aimed to investigate the protective effects of PEBP on UVB-induced skin inflammation. Topical preparations of polyphenols were applied to the skin of dorsally shaved mice. Mice were subsequently exposed to UVB and were sacrificed 90 min after UVB exposure. This study revealed that pretreatment with PEBP significantly inhibited UVB-induced recruitment of mast and neutrophil cells and prevented the loss of skin thickness. Furthermore, the findings show that PEBP treatment resulted in the downregulation of miR-210, 146a, and 155 and the upregulation of miR-200c and miR-205 compared to the UVB-irradiated mice. Additionally, PEBP was found to reduce the expression of IL-6, IL-1β, and TNFα, inhibiting COX-2 and increasing IL-10 after UVB exposure. Moreover, DNA methylation analysis indicated that PEBP might potentially reduce the activation of inflammation-related pathways such as MAPK, Wnt, Notch, and PI3K-AKT signaling. Our finding suggests that topical application of PEBP treatment may effectively prevent UVB-induced skin damage by inhibiting inflammation.
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- 2023
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32. Novel Probiotic Bacterium Rouxiella badensis subsp. acadiensis (Canan SV-53) Modulates Gut Immunity through Epigenetic Mechanisms.
- Author
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Shahbazi R, Yasavoli-Sharahi H, Mallet JF, Sharifzad F, Alsadi N, Cuenin C, Cahais V, Chung FF, Herceg Z, and Matar C
- Abstract
Gut immune system homeostasis is crucial to overall host health. Immune disturbance at the gut level may lead to systemic and distant sites' immune dysfunction. Probiotics and prebiotics consumption have been shown to improve gut microbiota composition and function and enhance gut immunity. In the current study, the immunomodulatory and anti-inflammatory effects of viable and heat-inactivated forms of the novel probiotic bacterium Rouxiella badensis subsp. acadiensis (Canan SV-53), as well as the prebiotic protocatechuic acid (PCA) derived from the fermentation of blueberry juice by SV-53, were examined. To this end, female Balb/c mice received probiotic (viable or heat-inactivated), prebiotic, or a mixture of viable probiotic and prebiotic in drinking water for three weeks. To better decipher the immunomodulatory effects of biotics intake, gut microbiota, gut mucosal immunity, T helper-17 (Th17) cell-related cytokines, and epigenetic modulation of Th17 cells were studied. In mice receiving viable SV-53 and PCA, a significant increase was noted in serum IgA levels and the number of IgA-producing B cells in the ileum. A significant reduction was observed in the concentrations of proinflammatory cytokines, including interleukin (IL)-17A, IL-6, and IL-23, and expression of two proinflammatory miRNAs, miR-223 and miR425, in treated groups. In addition, heat-inactivated SV-53 exerted immunomodulatory properties by elevating the IgA concentration in the serum and reducing IL-6 and IL-23 levels in the ileum. DNA methylation analysis revealed the role of heat-inactivated SV-53 in the epigenetic regulation of genes related to Th17 and IL-17 production and function, including Il6 , Il17rc , Il9 , Il11 , Akt1 , Ikbkg , Sgk1 , Cblb , and Smad4 . Taken together, these findings may reflect the potential role of the novel probiotic bacterium SV-53 and prebiotic PCA in improving gut immunity and homeostasis. Further studies are required to ascertain the beneficial effects of this novel bacterium in the inflammatory state.
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- 2023
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33. Lentinula edodes Cultured Extract and Rouxiella badensis subsp. acadiensis (Canan SV-53) Intake Alleviates Immune Deregulation and Inflammation by Modulating Signaling Pathways and Epigenetic Mechanisms.
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Shahbazi R, Yasavoli-Sharahi H, Alsadi N, Sharifzad F, Fang S, Cuenin C, Cahais V, Chung FF, Herceg Z, and Matar C
- Subjects
- Mice, Animals, Female, Lipopolysaccharides toxicity, Sexual Maturation, Prebiotics, Signal Transduction, Cytokines metabolism, Inflammation, Epigenesis, Genetic, Interleukin-17 metabolism, Shiitake Mushrooms metabolism
- Abstract
Puberty is a critical developmental period of life characterized by marked physiological changes, including changes in the immune system and gut microbiota development. Exposure to inflammation induced by immune stressors during puberty has been found to stimulate central inflammation and lead to immune disturbance at distant sites from the gut; however, its enduring effects on gut immunity are not well explored. Therefore, in this study, we used a pubertal lipopolysaccharides (LPS)-induced inflammation mouse model to mimic pubertal exposure to inflammation and dysbiosis. We hypothesized that pubertal LPS-induced inflammation may cause long-term dysfunction in gut immunity by enduring dysregulation of inflammatory signaling and epigenetic changes, while prebiotic/probiotic intake may mitigate the gut immune system deregulation later in life. To this end, four-week-old female Balb/c mice were fed prebiotics/probiotics and exposed to LPS in the pubertal window. To better decipher the acute and enduring immunoprotective effects of biotic intake, we addressed the effect of treatment on interleukin (IL)-17 signaling related-cytokines and pathways. In addition, the effect of treatment on gut microbiota and epigenetic alterations, including changes in microRNA (miRNA) expression and DNA methylation, were studied. Our results revealed a significant dysregulation in selected cytokines, proteins, and miRNAs involved in key signaling pathways related to IL-17 production and function, including IL-17A and F, IL-6, IL-1β, transforming growth factor-β (TGF-β), signal transducer and activator of transcription-3 (STAT3), p-STAT3, forkhead box O1 (FOXO1), and miR-145 in the small intestine of adult mice challenged with LPS during puberty. In contrast, dietary interventions mitigated the lasting adverse effects of LPS on gut immune function, partly through epigenetic mechanisms. A DNA methylation analysis demonstrated that enduring changes in gut immunity in adult mice might be linked to differentially methylated genes, including Lpb , Rorc , Runx1 , Il17ra , Rac1 , Ccl5 , and Il10 , involved in Th17 cell differentiation and IL-17 production and signaling. In addition, prebiotic administration prevented LPS-induced changes in the gut microbiota in pubertal mice. Together, these results indicate that following a healthy diet rich in prebiotics and probiotics is an optimal strategy for programming immune system function in the critical developmental windows of life and controlling inflammation later in life.
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- 2023
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34. Implication of KDM6A in bladder cancer.
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Matar M, Prince G, Hamati I, Baalbaky M, Fares J, Aoude M, Matar C, and Kourie HR
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- Humans, Histone Demethylases genetics, Urinary Bladder pathology, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms pathology
- Abstract
Background: Bladder cancer is a common urogenital malignancy characterized by frequent genetic alterations. Histone demethylase gene KDM6A is commonly mutated in bladder cancer. Aim: To review the characteristics of KDM6A and its mutation consequences, and to introduce a potential KDM6A-targeted treatment. Methods: We conducted a comprehensive literature search using two electronic databases, MEDLINE and Cochrane Library, to retrieve topic-related articles from July 2013 to July 2022 using keywords 'KDM6A', 'bladder cancer', 'UTX', 'treatment' and 'mutation'. Five reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted and 30 articles were retained. Main Results: A total of 30 articles were retrieved. Experimental and clinical data were collected and grouped by theme. Therapeutic strategies are depicted and organized by tables for a better understanding. Conclusion: This review demonstrates that KDM6A has crucial implications in bladder cancer pathogenesis and treatment.
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- 2023
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35. Evaluation of Rouxiella badensis Subsp Acadiensis (Canan SV-53) as a Potential Probiotic Bacterium.
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Novotny-Nuñez I, Perdigón G, Matar C, Martínez Monteros MJ, Yahfoufi N, Cazorla SI, and Maldonado-Galdeano C
- Abstract
The advent of omic platforms revealed the significant benefits of probiotics in the prevention of many infectious diseases. This led to a growing interest in novel strains of probiotics endowed with health characteristics related to microbiome and immune modulation. Therefore, autochthonous bacteria in plant ecosystems might offer a good source for novel next-generation probiotics. The main objective of this study was to analyze the effect of Rouxiella badensis acadiensis Canan ( R. acadiensis) a bacterium isolated from the blueberry biota, on the mammalian intestinal ecosystem and its potential as a probiotic microorganism. R . acadiensis , reinforced the intestinal epithelial barrier avoiding bacterial translocation from the gut to deep tissues, even after feeding BALB/c mice for a prolonged period of time. Moreover, diet supplementation with R. acadiensis led to increases in the number of Paneth cells, well as an increase in the antimicrobial peptide α defensin. The anti-bacterial effect of R . acadiensis against Staphylococcus aureus and Salmonella enterica serovar Typhimurium was also reported. Importantly, R. acadiensis -fed animals showed better survival in an in vivo Salmonella enterica serovar Typhimurium challenge compared with those that received a conventional diet. These results demonstrated that R. acadiensis possesses characteristics of a probiotic strain by contributing to the reinforcement and maintenance of intestinal homeostasis.
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- 2023
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36. Complete PacBio Single-Molecule Real-Time Sequence of a Novel Probiotic-Like Bacterium, Rouxiella badensis subsp. acadiensis , Isolated from the Biota of Wild Blueberries in the Acadian Forest.
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Salvetti E, Tremblay J, Arbour M, Mallet JF, Masson L, and Matar C
- Abstract
The PacBio whole-genome sequencing of the potential probiotic strain Canan SV-53T recovered from lowbush blueberries demonstrates high homology to Rouxiella badensis but with distinct enough clusters to propose the name Rouxiella badensis subsp. acadiensis . The sequencing also detected the presence of two native plasmids., Competing Interests: The authors declare no conflict of interest.
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- 2023
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37. Role of a Mixture of Polyphenol Compounds Released after Blueberry Fermentation in Chemoprevention of Mammary Carcinoma: In Vivo Involvement of miR-145.
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Mallet JF, Shahbazi R, Alsadi N, Saleem A, Sobiesiak A, Arnason JT, and Matar C
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- Animals, Female, Mice, Cell Line, Tumor, Cell Proliferation, Chemoprevention, Fermentation, Gallic Acid pharmacology, Gene Expression Regulation, Neoplastic, Mammary Neoplasms, Animal drug therapy, Mammary Neoplasms, Animal genetics, Mammary Neoplasms, Animal metabolism, Humans, Blueberry Plants chemistry, MicroRNAs drug effects, MicroRNAs metabolism, Polyphenols pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms metabolism
- Abstract
Epigenetic mechanisms such as microRNA (miRNA) deregulation seem to exert a central role in breast cancer initiation and progression. Therefore, targeting epigenetics deregulation may be an effective strategy for preventing and halting carcinogenesis. Studies have revealed the significant role of naturally occurring polyphenolic compounds derived from fermented blueberry fruits in cancer chemoprevention by modulation of cancer stem cell development through the epigenetic mechanism and regulation of cellular signaling pathways. In this study, we first investigated the phytochemical changes during the blueberry fermentation process. Fermentation favored the release of oligomers and bioactive compounds such as protocatechuic acid (PCA), gallic acid, and catechol. Next, we investigated the chemopreventive potentials of a polyphenolic mixture containing PCA, gallic acid, and catechin found in fermented blueberry juice in a breast cancer model by measuring miRNA expression and the signaling pathways involved in breast cancer stemness and invasion. To this end, 4T1 and MDA-MB-231 cell lines were treated with different doses of the polyphenolic mixture for 24 h. Additionally, female Balb/c mice were fed with this mixture for five weeks; two weeks before and three weeks after receiving 4T1 cells. Mammosphere formation was assayed in both cell lines and the single-cell suspension obtained from the tumor. Lung metastases were counted by isolating 6-thioguanine-resistant cells present in the lungs. In addition, we conducted RT-qPCR and Western blot analysis to validate the expression of targeted miRNAs and proteins, respectively. We found a significant reduction in mammosphere formation in both cell lines treated with the mixture and in tumoral primary cells isolated from mice treated with the polyphenolic compound. The number of colony-forming units of 4T1 cells in the lungs was significantly lower in the treatment group compared to the control group. miR-145 expression significantly increased in the tumor samples of mice treated with the polyphenolic mixture compared to the control group. Furthermore, a significant increase in FOXO1 levels was noted in both cell lines treated with the mixture. Overall, our results show that phenolic compounds found in fermented blueberry delay the formation of tumor-initiating cells in vitro and in vivo and reduce the spread of metastatic cells. The protective mechanisms seem to be related, at least partly, to the epigenetic modulation of mir-145 and its signaling pathways.
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- 2023
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38. Pubertal consumption of R. badensis subspecies acadiensis modulates LPS-induced immune responses and gut microbiome dysbiosis in a sex-specific manner.
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Yahfoufi N, Kadamani AK, Aly S, Al Sharani S, Liang J, Butcher J, Stintzi A, Matar C, and Ismail N
- Subjects
- Female, Male, Mice, Animals, Immunity, Illness Behavior, Lymphatic System
- Abstract
Puberty is a critical period of development characterized by significant brain remodeling and increased vulnerability to immune challenges. Exposure to an immune challenge such as LPS during puberty can result in inflammation and gut dysbiosis which may lead to altered brain functioning and psychiatric illnesses later in life. However, treatment with probiotics during puberty has been found to mitigate LPS-induced peripheral and central inflammation, prevent LPS-induced changes to the gut microbiota and protect against enduring behavioural disorders in a sex-specific manner. Recent findings from our laboratory revealed that pubertal R. badensis subspecies acadiensis (R. badensis subsp. acadiensis) treatment prevents LPS-induced depression-like behavior and alterations in 5HT1A receptor expression in a sex-specific manner. However, the underlying mechanism remains unclear. Thus, the aim of this study was to gain mechanistic insights and to investigate the ability of R. badensis subsp. acadiensis consumption during puberty to mitigate the effects of LPS treatment on the immune system and the gut microbiome. Our results revealed that pubertal treatment with R. badensis subsp. acadiensis reduced sickness behaviors in females more than males in a time-specific manner. It also mitigated LPS-induced increases in pro-inflammatory cytokines in the blood and in TNFα mRNA expression in the prefrontal cortex and the hippocampus of female mice. There were sex-dependent differences in microbiome composition that persisted after LPS injection or R. badensis subsp. acadiensis consumption. R. badensis subsp. acadiensis had greater impact on the microbiota of male mice but female microbiota's were more responsive to LPS treatment. This suggested that female mice microbiota's may be more prone to modulation by this probiotic. These findings emphasize the sex-specific effects of probiotic use during puberty on the structure of the gut microbiome and the immune system and highlight the critical role of gut colonization with probiotics during adolescence on immunomodulation and prevention of the enduring effects of infections., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AS is a co-founder of MedBiome, a clinical microbiomics company. Rouxiella badensis subsp. acadiensis has been filed in a U.S. Provisional Application No. 62/916,921 titled “Probiotics Composition and Methods” for its potential probiotic effects (Matar et al. 2020)., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2023
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39. miRNA-200b Signature in the Prevention of Skin Cancer Stem Cells by Polyphenol-enriched Blueberry Preparation.
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Alsadi N, Mallet JF, and Matar C
- Abstract
Exposure of the skin to solar UV radiation leads to inflammation, DNA damage, and dysregulation of cellular signaling pathways, which may cause skin cancer. Photochemoprevention with natural products is an effective strategy for the control of cutaneous neoplasia. Polyphenols have been proven to help prevent skin cancer and to inhibit the growth of cancer stem cells (CSCs) through epigenetic mechanisms, including modulation of microRNAs expression. Thus, the current study aimed to assess the effect of polyphenol enriched blueberry preparation (PEBP) or non-fermented blueberry juice (NBJ) on expression of miRNAs and target proteins associated with different clinicopathological characteristics of skin cancer such as stemness, motility, and invasiveness. We observed that PEBP significantly inhibited the proliferation of skin CSCs derived from different melanoma cell lines, HS 294T and B16F10. Moreover, PEBP was able to reduce the formation of melanophores. We also showed that the expression of the CD133
+ stem cell marker in B16F10 and HS294T cell lines was significantly decreased after treating the cells with PEBP in comparison to the NBJ and control groups. Importantly, tumor suppressors' miR-200s, involved in the regulation of the epithelial-to-mesenchymal transition and metastasis, were strikingly upregulated. In addition, we have shown that a protein target of the tumor suppressor miR200b, ZEB1, was also significantly modulated. Thus, the results demonstrates that PEBP possesses potent anticancer and anti-metastatic potentials and may represent a novel chemopreventative agent against skin cancer., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed., (Copyright © 2021 Korean Society of Cancer Prevention.)- Published
- 2021
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40. Polyphenol-Enriched Blueberry Preparation Controls Breast Cancer Stem Cells by Targeting FOXO1 and miR-145.
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Mallet JF, Shahbazi R, Alsadi N, and Matar C
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- Animals, Antineoplastic Agents, Phytogenic chemistry, Blueberry Plants chemistry, Breast Neoplasms genetics, Breast Neoplasms pathology, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Mice, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Polyphenols chemistry, Antineoplastic Agents, Phytogenic pharmacology, Breast Neoplasms drug therapy, Forkhead Box Protein O1 genetics, MicroRNAs genetics, Neoplastic Stem Cells drug effects, Polyphenols pharmacology
- Abstract
Scientific evidence supports the early deregulation of epigenetic profiles during breast carcinogenesis. Research shows that cellular transformation, carcinogenesis, and stemness maintenance are regulated by epigenetic-specific changes that involve microRNAs (miRNAs). Dietary bioactive compounds such as blueberry polyphenols may modulate susceptibility to breast cancer by the modulation of CSC survival and self-renewal pathways through the epigenetic mechanism, including the regulation of miRNA expression. Therefore, the current study aimed to assay the effect of polyphenol enriched blueberry preparation (PEBP) or non-fermented blueberry juice (NBJ) on the modulation of miRNA signature and the target proteins associated with different clinical-pathological characteristics of breast cancer such as stemness, invasion, and chemoresistance using breast cancer cell lines. To this end, 4T1 and MB-MDM-231 cell lines were exposed to NBJ or PEBP for 24 h. miRNA profiling was performed in breast cancer cell cultures, and RT-qPCR was undertaken to assay the expression of target miRNA. The expression of target proteins was examined by Western blotting. Profiling of miRNA revealed that several miRNAs associated with different clinical-pathological characteristics were differentially expressed in cells treated with PEBP. The validation study showed significant downregulation of oncogenic miR-210 expression in both 4T1 and MDA-MB-231 cells exposed to PEBP. In addition, expression of tumor suppressor miR-145 was significantly increased in both cell lines treated with PEBP. Western blot analysis showed a significant increase in the relative expression of FOXO1 in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Furthermore, a significant decrease was observed in the relative expression of N-RAS in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Our data indicate a potential chemoprevention role of PEBP through the modulation of miRNA expression, particularly miR-210 and miR-145, and protection against breast cancer development and progression. Thus, PEBP may represent a source for novel chemopreventative agents against breast cancer.
- Published
- 2021
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41. Immunomodulation and Intestinal Morpho-Functional Aspects of a Novel Gram-Negative Bacterium Rouxiella badensis subsp. acadiensis .
- Author
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Yahfoufi N, Alsadi N, Mallet JF, Kulshreshtha G, Hincke M, Ismail N, and Matar C
- Abstract
A novel bacterium ( Rouxiella badensis subsp. acadiensis ) isolated from the microbiota of wild blueberry fruit was investigated for its immunomodulation capabilities and intestinal morpho-functional aspects. The whole-genome shotgun sequencing of this bacterium led to its new taxonomy and showed absence of pathogenicity genes. Although the bacterium was used for blueberry-fermentation and enhancing its anti-inflammatory effects on neurodegeneration, diabetes, and cancer, no study has assessed the effect of the bacterium on health. In this study, we used several in vitro and in vivo assays to evaluate the interaction of R. badensis subsp. acadiensis with the intestinal mucosa and its impact on the localized immune response. The strain antibiotic susceptibility has been investigated as well as its tolerance to gastric and intestinal environment and ability to attach to human intestinal epithelial cells (Caco-2 and HT-29). In addition, Balb/c mice were used to explore the immune-modulatory characteristics of the live bacterium at the intestinal level and its impact on the morpho-functional aspects of the intestinal mucosa. In vitro assays revealed the ability of R. badensis subsp. acadiensis to survive the gastric and intestinal simulated conditions and to satisfactorily adhere to the human intestinal epithelial cells. The bacterium was shown to be sensitive to an array of antibiotics. Immuno-modulation studies with mice orally administered with R. badensis subsp. acadiensis showed a higher number of IgA positive cells in the small intestine, a higher concentration of the anti-inflammatory cytokine IL-10 in the intestinal mucosa, as well as an increase in the number of goblet cells. The anti-inflammatory cytokine miR146a was found to be increased in the ileum and brain. Furthermore, it increases the number of goblet cells which contribute to intestinal barrier integrity. Taken together, our findings reflect the ability of the tested bacterium to modulates the intestinal homeostasis and immune response. Detailed safety unpublished studies and genome data support our finding. The strain Rouxiella badensis subsp. acadiensis has been filed in a provisional patent; a U.S. Provisional Application No. 62/916,921 entitled "Probiotics Composition and Methods." Future studies are still needed to validate the potential utilization of this strain as functional food and its potential probiotic effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yahfoufi, Alsadi, Mallet, Kulshreshtha, Hincke, Ismail and Matar.)
- Published
- 2021
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42. Adolescent use of potential novel probiotic Rouxiella badensis subsp. acadiensis ( Canan SV-53 ) mitigates pubertal LPS-Induced behavioral changes in adulthood in a sex-specific manner by modulating 5HT1A receptors expression in specific brain areas.
- Author
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Yahfoufi N, Ah-Yen EG, Chandrasegaram R, Aly S, Murack M, Kadamani AK, Matar C, and Ismail N
- Abstract
Adolescence is a critical period of development during which the brain undergoes significant remodeling that impacts behavior later in life. Exposure to stress, and especially immune challenge, during this period triggers changes in brain function resulting in the development of mental disorders in adulthood, such as depression and anxiety. Previous studies from our laboratory have shown that a single exposure to LPS (lipopolysaccharide) during puberty causes enduring depression-like behaviour in females and anxiety-like behaviours in males. However, administration of probiotics during puberty blocked the enduring effects of LPS on depression-like and anxiety-like behaviors in female and male mice, respectively. These results suggest that the gut microbiome is a mediator of the effects of stress on mental health. The objective of the current study is to examine the effectiveness of a novel probiotic Rouxiella badensis subsp. acadiensis (Canan SV-53) in blocking LPS-induced anxiety-like and depression-like behaviors in adult male and female mice. Our results showed that Rouxiella badensis subsp. acadiensis (Canan SV-53) blocked LPS-induced depression-like behavior in female mice. We also found that pubertal treatment with Rouxiella badensis subsp. acadiensis (Canan SV-53) mitigated the LPS-induced decrease in 5HT1A expression in CA1 as well as the LPS-induced increase in 5HT1A expression in the raphe-nuclei in female mice. Contrary to our predictions, pubertal LPS treatment at 6 weeks of age did not induce enduring anxiety-like behavior in males. There was also no difference in anxiety-like behavior between the LPS-sucrose and LPS-probiotic male groups. However, pubertal LPS treatment increased the expression of 5HT1A receptors in the DRN in males, while probiotic exposure mitigated this increase. Our study highlights the consequences of stress exposure (immune challenge) on mental health in adulthood taking into consideration 5HT1A receptors expression at different regions of the brain. It also emphasizes on the importance of considering adolescence as window of opportunities during which probiotic use can alleviate the long-term neural and behavioral alterations induced by stress., Competing Interests: We have no conflict to declare., (© 2021 The Authors.)
- Published
- 2021
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43. Pubertal immune challenge suppresses the hypothalamic-pituitary-gonadal axis in male and female mice.
- Author
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Smith KB, Murray E, Chandrasegaram R, Liang J, Mallet JF, Matar C, Blaustein JD, and Ismail N
- Subjects
- Animals, Female, Follicle Stimulating Hormone blood, Hypothalamus metabolism, Lipopolysaccharides pharmacology, Luteinizing Hormone blood, Male, Mice, Hypothalamo-Hypophyseal System metabolism, Hypothalamus drug effects, Kisspeptins metabolism, Receptors, Kisspeptin-1 metabolism
- Abstract
Kisspeptin is a neuropeptide responsible for propagating the hypothalamic-pituitary-gonadal (HPG) axis and initiating puberty. Pubertal exposure to an immune challenge causes enduring sexual behavior dysfunction in males and females, but the mechanism underlying this stress-induced sexual dysfunction remains unknown. Previous findings show that stress exposure can downregulate the HPG axis in adult females. However, it is unclear whether stress induced HPG axis suppression is limited to adult females or also extends to males and to pubertal animal models. The current study was designed to investigate the sex-specific consequences of a pubertal immune challenge on specific components of the HPG axis. Six-week old pubertal male and female mice were treated with saline or with lipopolysaccharide, a bacterial endotoxin. Expression of hypothalamic Kiss1 and Kiss1R as well as serum concentrations of luteinizing hormone, follicle-stimulating hormone, and growth hormone were examined. Pubertal lipopolysaccharide treatment decreased hypothalamic Kiss1, but not Kiss1R, expression in both males and females. Furthermore, only males showed decreases in circulating luteinizing and follicle-stimulating hormones. These results show that pubertal immune challenge suppresses the HPG axis by inhibiting Kiss1 production and decreasing serum gonadotropin concentrations in pubertal males, but points to a different mechanism in pubertal females., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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44. Anti-Inflammatory and Immunomodulatory Properties of Fermented Plant Foods.
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Shahbazi R, Sharifzad F, Bagheri R, Alsadi N, Yasavoli-Sharahi H, and Matar C
- Subjects
- Anti-Inflammatory Agents chemistry, Humans, Anti-Inflammatory Agents pharmacology, Fermented Foods, Immunomodulation
- Abstract
Fermented plant foods are gaining wide interest worldwide as healthy foods due to their unique sensory features and their health-promoting potentials, such as antiobesity, antidiabetic, antihypertensive, and anticarcinogenic activities. Many fermented foods are a rich source of nutrients, phytochemicals, bioactive compounds, and probiotic microbes. The excellent biological activities of these functional foods, such as anti-inflammatory and immunomodulatory functions, are widely attributable to their high antioxidant content and lactic acid-producing bacteria (LAB). LAB contribute to the maintenance of a healthy gut microbiota composition and improvement of local and systemic immunity. Besides, antioxidant compounds are involved in several functional properties of fermented plant products by neutralizing free radicals, regulating antioxidant enzyme activities, reducing oxidative stress, ameliorating inflammatory responses, and enhancing immune system performance. Therefore, these products may protect against chronic inflammatory diseases, which are known as the leading cause of mortality worldwide. Given that a large body of evidence supports the role of fermented plant foods in health promotion and disease prevention, we aim to discuss the potential anti-inflammatory and immunomodulatory properties of selected fermented plant foods, including berries, cabbage, and soybean products, and their effects on gut microbiota.
- Published
- 2021
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45. Characterization of Critical Determinants of ACE2-SARS CoV-2 RBD Interaction.
- Author
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Brown EEF, Rezaei R, Jamieson TR, Dave J, Martin NT, Singaravelu R, Crupi MJF, Boulton S, Tucker S, Duong J, Poutou J, Pelin A, Yasavoli-Sharahi H, Taha Z, Arulanandam R, Surendran A, Ghahremani M, Austin B, Matar C, Diallo JS, Bell JC, Ilkow CS, and Azad T
- Subjects
- Amino Acid Sequence, Angiotensin-Converting Enzyme 2 genetics, Antibodies, Neutralizing immunology, Antiviral Agents pharmacology, Binding Sites, COVID-19 immunology, HEK293 Cells, Host Microbial Interactions, Humans, Models, Molecular, Mutation, Protein Binding, Protein Interaction Domains and Motifs, Receptors, Virus chemistry, Receptors, Virus metabolism, SARS-CoV-2 drug effects, Sequence Alignment, COVID-19 Drug Treatment, Angiotensin-Converting Enzyme 2 chemistry, Angiotensin-Converting Enzyme 2 metabolism, COVID-19 metabolism, COVID-19 virology, SARS-CoV-2 metabolism, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus metabolism
- Abstract
Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. In this study, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2, by utilizing our recently developed NanoBiT technology-based biosensor as well as pseudotyped-virus infectivity assays. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, efficacy of competitive inhibitors, as well as neutralizing antibody activity. We also look at the implications the mutations may have on virus transmissibility, host susceptibility, and the virus transmission path to humans. These critical determinants of virus-host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity.
- Published
- 2021
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46. Probiotics in Treatment of Viral Respiratory Infections and Neuroinflammatory Disorders.
- Author
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Shahbazi R, Yasavoli-Sharahi H, Alsadi N, Ismail N, and Matar C
- Subjects
- Betacoronavirus drug effects, Betacoronavirus pathogenicity, Betacoronavirus physiology, Brain immunology, COVID-19, Coronavirus Infections immunology, Coronavirus Infections microbiology, Coronavirus Infections virology, Gastrointestinal Microbiome immunology, Gastrointestinal Tract immunology, Gastrointestinal Tract microbiology, Humans, Immunomodulation, Influenza, Human immunology, Influenza, Human microbiology, Influenza, Human virology, Lung immunology, Mental Disorders immunology, Mental Disorders microbiology, Microbial Consortia immunology, Multiple Sclerosis immunology, Multiple Sclerosis microbiology, Orthomyxoviridae drug effects, Orthomyxoviridae pathogenicity, Orthomyxoviridae physiology, Pandemics, Pneumonia, Viral immunology, Pneumonia, Viral microbiology, Pneumonia, Viral virology, Respiratory Tract Infections immunology, Respiratory Tract Infections microbiology, SARS-CoV-2, Symbiosis immunology, Coronavirus Infections therapy, Influenza, Human therapy, Mental Disorders therapy, Multiple Sclerosis therapy, Pneumonia, Viral therapy, Probiotics therapeutic use, Respiratory Tract Infections therapy
- Abstract
Inflammation is a biological response to the activation of the immune system by various infectious or non-infectious agents, which may lead to tissue damage and various diseases. Gut commensal bacteria maintain a symbiotic relationship with the host and display a critical function in the homeostasis of the host immune system. Disturbance to the gut microbiota leads to immune dysfunction both locally and at distant sites, which causes inflammatory conditions not only in the intestine but also in the other organs such as lungs and brain, and may induce a disease state. Probiotics are well known to reinforce immunity and counteract inflammation by restoring symbiosis within the gut microbiota. As a result, probiotics protect against various diseases, including respiratory infections and neuroinflammatory disorders. A growing body of research supports the beneficial role of probiotics in lung and mental health through modulating the gut-lung and gut-brain axes. In the current paper, we discuss the potential role of probiotics in the treatment of viral respiratory infections, including the COVID-19 disease, as major public health crisis in 2020, and influenza virus infection, as well as treatment of neurological disorders like multiple sclerosis and other mental illnesses.
- Published
- 2020
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47. Adolescence and Aging: Impact of Adolescence Inflammatory Stress and Microbiota Alterations on Brain Development, Aging, and Neurodegeneration.
- Author
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Yahfoufi N, Matar C, and Ismail N
- Subjects
- Adolescent, Aging physiology, Aging psychology, Humans, Inflammation complications, Stress, Psychological complications, Aging pathology, Brain pathology, Gastrointestinal Microbiome physiology, Inflammation pathology, Neurodegenerative Diseases etiology, Stress, Psychological pathology
- Abstract
Puberty/adolescence is a critical phase during neurodevelopment with numerous structural, neurochemical, and molecular changes occurring in response to genetic and environmental signals. A consequence of this major neuronal reorganizing and remodeling is a heightened level of vulnerability to stressors and immune challenges. The gut microbiota is a fundamental modulator of stress and immune responses and has been found to play a role in mental health conditions and neurodegenerative disorders. Environmental insults (stress, infection, neuroinflammation, and use of antibiotics) during adolescence can result in dysbiosis subsidizing the development of brain disorders later in life. Also, pubertal neuroinflammatory insults can alter neurodevelopment, impact brain functioning in an enduring manner, and contribute to neurological disorders related to brain aging, such as Alzheimer's disease, Parkinson's disease, and depression. Exposure to probiotics during puberty can mitigate inflammation, reverse dysbiosis, and decrease vulnerabilities to brain disorders later in life. The goal of this review is to reveal the consequences of pubertal exposure to stress and immune challenges on the gut microbiota, immune reactivity within the brain, and the risk or resilience to stress-induced mental illnesses and neurodegenerative disorders. We propose that the consumption of probiotics during adolescence contribute to the prevention of brain pathologies in adulthood., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.)
- Published
- 2020
- Full Text
- View/download PDF
48. Probiotic consumption during puberty mitigates LPS-induced immune responses and protects against stress-induced depression- and anxiety-like behaviors in adulthood in a sex-specific manner.
- Author
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Murray E, Sharma R, Smith KB, Mar KD, Barve R, Lukasik M, Pirwani AF, Malette-Guyon E, Lamba S, Thomas BJ, Sadeghi-Emamchaie H, Liang J, Mallet JF, Matar C, and Ismail N
- Subjects
- Animals, Anxiety drug therapy, Anxiety metabolism, Anxiety Disorders drug therapy, Anxiety Disorders metabolism, Behavior, Animal physiology, Cytokines metabolism, Depression drug therapy, Depression metabolism, Depressive Disorder drug therapy, Depressive Disorder metabolism, Female, Gastrointestinal Microbiome drug effects, Illness Behavior drug effects, Inflammation metabolism, Lipopolysaccharides pharmacology, Male, Mice, Sex Factors, Gastrointestinal Microbiome physiology, Probiotics pharmacology, Sexual Maturation drug effects
- Abstract
Puberty/adolescence is a significant period of development and a time with a high emergence of psychiatric disorders. During this period, there is increased neuroplasticity and heightened vulnerability to stress and inflammation. The gut microbiome regulates stress and inflammatory responses and can alter brain chemistry and behaviour. However, the role of the gut microbiota during pubertal development remains largely uninvestigated. The current study examined gut manipulation with probiotics during puberty in CD1 mice on lipopolysaccharide (LPS)-induced immune responses and enduring effects on anxiety- and depression-like behaviours and stress-reactivity in adulthood. Probiotics reduced LPS-induced sickness behaviour at 12 h in females and at 48 h following LPS treatment in males. Probiotics also reduced LPS-induced changes in body weight at 48 h post-treatment in females. Probiotic treatment also prevented LPS-induced increases in pro- and anti-inflammatory peripheral cytokines at 8 h following LPS treatment, reduced central cytokine mRNA expression in the hypothalamus, hippocampus and PFC, and prevented LPS-induced changes to in the gut microbiota. A single exposure to LPS during puberty resulted in enduring depression-like behaviour in female mice, and anxiety-like behaviour in male mice in adulthood. However, pubertal exposure to probiotics prevented enduring LPS-induced depression-like behaviour in females and anxiety-like behaviors in males. Moreover, probiotics altered toll-like receptor-4 activity in the paraventricular nucleus of the hypothalamus (PVN) in males in response to a novel stressor in adulthood. Our results suggest that the gut microbiome plays an important role in pubertal neurodevelopment. These findings indicate that exposure to probiotics during puberty mitigates inflammation and decreases stress-induced vulnerabilities to emotional behaviours later in life, in a sex-specific manner., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
49. Perceptions and Attitudes of Cancer Patients and Caregivers Towards Enrollment in Clinical Trials in Lebanon.
- Author
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Salem R, Matar C, Assi R, Alameddine R, Temraz S, Shamseddine A, and Mukherji D
- Subjects
- Adult, Aged, Aged, 80 and over, Caregivers, Female, Humans, Lebanon, Male, Middle Aged, Surveys and Questionnaires, Clinical Trials as Topic, Health Knowledge, Attitudes, Practice, Neoplasms, Patient Participation, Research Subjects
- Abstract
The rates of participation in oncology clinical trials (CTs) are relatively lower in the Middle East compared to other areas in the world. Many social and cultural factors underlie the patients' reluctance to participate. To probe the knowledge, attitudes, and perceptions of patients with cancer and their caregivers regarding participation in CTs at our tertiary referral center in Lebanon, we interviewed 210 patients and caregivers visiting the outpatient clinics in the Naef Basile Cancer Institute at the American University of Beirut. A questionnaire was derived from literature and administered in Arabic. The study was approved by the Institutional Review Board (IRB). Two hundred individuals agreed to answer the questionnaire. The majority of participants (90.5%) were Lebanese with the remaining being non-Lebanese Arabs. Eighty-nine participants (45%) were aware of the concepts of CTs. Eighty-two respondents (41%) would participate in phase I CTs. Twenty-nine individuals (14.5%) agree to be enrolled in CTs with the approval of their family members only. One hundred twenty-nine subjects (64.5%) stated that they would refuse enrollment in a CT where they might receive placebo. Eighty-eight (44%) of participants considered that medical records could be reviewed for research without consent while 54% agreed that samples collected during clinical workup could be used for research without the consent of the patient. There are several social and demographic correlates for participation in CTs. Raising awareness and overcoming barriers of misconception are keys to promote participation in CTs in Lebanon.
- Published
- 2019
- Full Text
- View/download PDF
50. Programming Effects of Pubertal Lipopolysaccharide Treatment in Male and Female CD-1 Mice.
- Author
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Sharma R, van Mil S, Melanson B, Thomas BJ, Rooke J, Mallet JF, Matar C, Schwarz JM, and Ismail N
- Subjects
- Animals, Female, Male, Mice, Immune System Phenomena drug effects, Lipopolysaccharides toxicity, Sexual Maturation immunology, Stress, Physiological immunology
- Abstract
Puberty is a critical period of development marked by sexual, immune, and neural maturation. Exposure to stress during this period can lead to enduring changes in brain functioning and in behavior; however, the underlying mechanisms and the programming effects of stress during puberty remain unknown. Therefore, the objective of this study was to investigate the programming effects of pubertal immune challenge in response to a homotypic stressor later in life in CD-1 mice. Age and sex differences in the peripheral and central cytokine levels, along with sickness behavior and telemetry data, were analyzed following the secondary treatment. The results showed that pretreatment with LPS attenuated the immune response to a second homotypic challenge. Males pretreated with LPS during puberty and in early adulthood displayed an attenuated hypothermic response following the second LPS treatment compared with saline-pretreated controls, which is consistent with the attenuated peripheral IL-6 and IFN-γ concentrations. Females pretreated with LPS during puberty displayed lower IL-1β, TNF-α, and IL-6 mRNA expression in the prefrontal cortex following the secondary immune challenge compared with saline controls. The results of this study show that exposure to LPS during puberty programs the peripheral and central immune responses, resulting in an attenuated immune response following a subsequent homotypic stressor. Thus, exposure to an immune challenge during puberty affects immune function later in life, which could permanently affect brain function and have implications on mental health., (Copyright © 2019 by The American Association of Immunologists, Inc.)
- Published
- 2019
- Full Text
- View/download PDF
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