1H-Pyrazol-3-amine, 5-phenyl-/1H-Pyrazol-5-amine, 3-phenyl-/3-Phenyl-1H-pyrazol-5-amine/3-Amino-5-phenylpyrazole
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Evidence suggests a role of intestinal microbiota-host interactions in the pathophysiology and symptoms of irritable bowel syndrome (IBS).
The objective of this article is to assess the effects of Lactobacillus paracasei CNCM I-1572 on clinical and gut microbiota-related factors in IBS.
We conducted a multicenter, randomized, double-blind, cross-over, 18-week, placebo-controlled, pilot trial assessing the effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota composition, fecal short chain fatty acid (SCFA), immunoglobulin A, and cytokines in IBS. The intestinal microbial ecosystem was characterized by 16S rRNA gene profiling.
Forty IBS patients were enrolled from five Italian centers. Lactobacillus paracasei CNCM I-1572 did not significantly improve IBS symptoms, including primary efficacy variables worst abdominal pain/discomfort and IBS degree of relief. Interestingly, Lactobacillus paracasei CNCM I-1572 induced a significant reduction in genus Ruminococcus, dominated by taxa related to Ruminococcus bromii and Ruminococcus callidus, a significant increase in the SCFAs acetate and butyrate, and a significant reduction in the pro-inflammatory cytokine interleukin-15.
This pilot study shows that Lactobacillus paracasei CNCM I-1572 is able to modulate gut microbiota structure/function and reduce immune activation in IBS. As no statistically significant effect on IBS-symptoms was found, further studies are necessary to determine the role of this probiotic in IBS. The study was registered at ClinicalTrials.gov registry under identifier NCT02371499.
Irritable bowel syndrome, dietary compounds, probiotics, microbiota
Effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: A pilot randomized clinical trial
Cesare Cremon,1 Simone Guglielmetti,2 Giorgio Gargari,2 Valentina Taverniti,2 Anna Maria Castellazzi,3 Chiara Valsecchi,3 Carlotta Tagliacarne,3 Walter Fiore,4 Massimo Bellini,5 Lorenzo Bertani,5 Dario Gambaccini,5 Michele Cicala,6 Bastianello Germanà,7 Maurizio Vecchi,8 Isabella Pagano,1 Maria Raffaella Barbaro,1 Lara Bellacosa,1 Vincenzo Stanghellini,1 and Giovanni Barbara1
Uterus transplantation (UTx) is an option for women with uterine factor infertility to have a child, but is still in the experimental stage. Therefore, allogeneic animal models of UTx are required for resolution of clinical issues. In this study, long-term outcomes were evaluated in four recipients (cases 1-4) after allogeneic UTx in cynomolgus macaques. Immunosuppression with antithymocyte globulin induction and a triple maintenance regimen was used. Postoperative ultrasonography and biopsy of the transplanted uterus and immunoserological examinations were performed. All four recipients survived for >3 months after surgery, but continuous menstruation did not resume, although temporary menstruation occurred (cases 1 and 2). All animals were euthanized due to irreversible rejection and no uterine blood flow (cases 1, 2 and 4) and post-transplant lymphoproliferative disorder (case 3). Donor-specific antibodies against MHC class I and II were detected in cases 1, 2 and 4, but not in case 3. Peripheral lymphocyte counts tended to elevate for CD3+, CD20+ and NK cells in conjunction with uterine rejection, and all animals had elevated stimulation indexes of mixed lymphocyte reaction after surgery. Establishment of allogeneic UTx in cynomolgus macaque requires further exploration of immunosuppression, but the clinicopathological features of uterine rejection are useful for development of human UTx.
uterus transplantation, uterine transplantation, cynomolgus macaque, uterine factor infertility, allogeneic uterus transplantation, rejection
Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques
Iori Kisu,1,* Hirohito Ishigaki,2 Katsura Emoto,3 Yojiro Kato,4 Yohei Yamada,5 Kentaro Matsubara,6 Hideaki Obara,6 Yohei Masugi,3 Yusuke Matoba,1 Masataka Adachi,1 Kouji Banno,1 Yoko Saiki,7 Iori Itagaki,8,9 Ikuo Kawamoto,8 Chizuru Iwatani,8 Takahiro Nakagawa,8 Hideaki Tsuchiya,8 Takako Sasamura,2 Hiroyuki Urano,10 Masatsugu Ema,8 Kazumasa Ogasawara,2,8 Daisuke Aoki,1 Kenshi Nakagawa,10 and Takashi Shiina11
Background: Following the publication of the 2018 World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) Third Expert Report, a collaborative group was formed to develop a standardized scoring system and provide guidance for research applications. Methods: The 2018 WCRF/AICR Cancer Prevention Recommendations, goals, and statements of advice were examined to define components of the new Score. Cut-points for scoring were based on quantitative guidance in the 2018 Recommendations and other guidelines, past research that operationalized 2007 WCRF/AICR Recommendations, and advice from the Continuous Update Project Expert Panel. Results: Eight of the ten 2018 WCRF/AICR Recommendations concerning weight, physical activity, diet, and breastfeeding (optional), were selected for inclusion. Each component is worth one point: 1, 0.5, and 0 points for fully, partially, and not meeting each recommendation, respectively (Score: 0 to 7-8 points). Two recommendations on dietary supplement use and for cancer survivors are not included due to operational redundancy. Additional guidance stresses the importance of accounting for other risk factors (e.g., smoking) in relevant models. Conclusions: The proposed 2018 WCRF/AICR Score is a practical tool for researchers to examine how adherence to the 2018 WCRF/AICR Recommendations relates to cancer risk and mortality in various adult populations.
cancer prevention, diet, weight, physical activity, breastfeeding, dietary guidelines, index score
Operationalizing the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations: A Standardized Scoring System
Marissa M. Shams-White,1,* Nigel T. Brockton,2 Panagiota Mitrou,3 Dora Romaguera,4,5,6 Susannah Brown,3 Alice Bender,2 Lisa L. Kahle,7 and Jill Reedy1