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Abstract Obesity is often associated with sex-dependent metabolic complications, in which altered intestinal barrier function and gut microbiota contribute. We aimed to characterize in mice the sex-dependent effects of a high fat diet on these parameters. Male and female C57BL/6 mice received a standard (SD) or high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14). Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic expression of 44 genes encoding factors involved in inflammatory response and gut barrier function, cecal microbiota, plasma adipokines and white adipose tissue response have been assessed. Both male and female HFD mice exhibited an increase of body weight and fat mass gain and glucose intolerance compared to SD mice. However, only male HFD mice tended to develop insulin resistance associated to increased Tnfα and Ccl2 mRNA expression in perigonadal adipose tissue. By contrast, only female HFD mice showed significant intestinal hyperpermeability that was associated with more markedly altered colonic inflammatory response. Cecal microbiota richness was markedly reduced in both sexes (Observed species) with sex-dependent modifications at the phyla or family level, e.g. decreased relative abundance of Bacillota and Lachnospiraceae in females, increased of Bacteroidaceae in males. Interestingly, some of these microbiota alterations were correlated with peripheral metabolic and inflammatory markers. In conclusions, male and female mice exhibit different responses to a high fat diet with specific changes of gut microbiota, intestinal barrier function, colonic and white adipose tissue inflammation, metabolic markers and body weight gain. The underlying mechanisms should be deciphered in further investigations.

Abstract Rationale Patients with anorexia nervosa (AN) often present sleep disorders and circadian hormonal dysregulation. The role of the microbiota–gut–brain axis in the regulation of feeding behavior has emerged during the last decades but its relationships with the circadian rhythm remains poorly documented. Thus, we aimed to characterize the circadian clock genes expression in peripheral and central tissues in the activity-based anorexia mouse model (ABA), as well as the dynamics of the gut–microbiota composition. Methods From day 1 to day 17, male and female C57Bl/6 mice were submitted or not to the ABA protocol (ABA and control (CT) groups), which combines a progressive limited access to food and a free access to a running wheel. At day 17, fasted CT and ABA mice were euthanized after either resting (EoR) or activity (EoA) phase (n = 10–12 per group). Circadian clock genes expression was assessed by RT-qPCR on peripheral (liver, colon and ileum) and central (hypothalamic suprachiasmatic nucleus or SCN) tissues. Cecal bacterial taxa abundances were evaluated by qPCR. Data were compared by two-way ANOVA followed by post-tests. Results ABA mice exhibited a lower food intake, a body weight loss and an increase of diurnal physical activity that differ according with the sex. Interestingly, in the SCN, only ABA female mice exhibited altered circadian clock genes expression (Bmal1, Per1, Per2, Cry1, Cry2). In the intestinal tract, modification of clock genes expression was also more marked in females compared to males. For instance, in the ileum, female mice showed alteration of Bmal1, Clock, Per1, Per2, Cry1, Cry2 and Rev-erbα mRNA levels, while only Per2 and Cry1 mRNAs were affected by ABA model in males. By contrast, in the liver, clock genes expression was more markedly affected in males compared to females in response to ABA. Finally, circadian variations of gut–bacteria abundances were observed in both male and female mice and sex-dependent alteration were observed in response to the ABA model. Conclusions This study shows that alteration of circadian clock genes expression at both peripheral and central levels occurs in response to the ABA model. In addition, our data underline that circadian variations of the gut–microbiota composition are sex-dependent.

The gut microbiota produces a wide variety of metabolites, which interact with intestinal cells and contribute to host physiology. The effect of gut commensal bacteria on host protein SUMOylation, an essential ubiquitin-like modification involved in various intestinal functions, remains, however, unknown. Here, we show that short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) produced by the gut microbiota increase protein SUMOylation in intestinal cells in a pH-dependent manner. We demonstrate that these metabolites inactivate intestinal deSUMOylases and promote the hyperSUMOylation of nuclear matrix-associated proteins. We further show that BCFAs inhibit the NF-κB pathway, decrease pro-inflammatory cytokine expression, and promote intestinal epithelial integrity. Together, our results reveal that fatty acids produced by gut commensal bacteria regulate intestinal physiology by modulating SUMOylation and illustrate a new mechanism of dampening of host inflammatory responses triggered by the gut microbiota.

Abstract Background The use of animal models with depleted intestinal microbiota has recently increased thanks to the huge interest in the potential role of these micro-organisms in human health. In particular, depletion of gut bacteria using antibiotics has recently become popular as it represents a low cost and easy alternative to germ-free animals. Various regimens of antibiotics are used in the literature, which differ in composition, dose, length of treatment and mode of administration. In order to help investigators in choosing the most appropriate protocol for their studies, we compared here three modes of antibiotic delivery to deplete gut bacteria in C57Bl/6 mice. We delivered one of the most frequently used combination of antibiotics (a mix of ampicillin, neomycin, metronidazole and vancomycin) either ad libitum in drinking water or by oral gavage once or twice per day. Results We quantified the global bacterial density, as well as the abundance of specific bacterial and fungal taxa, in mouse feces in response to antibiotics exposure. We observed that oral gavage once a day with antibiotics is not a reliable method as it occasionally triggers hyperproliferation of bacteria belonging to the Escherichia/Shigella taxon and leads, as a consequence, to a moderate decrease in fecal bacterial density. Antibiotics delivery by oral gavage twice a day or in drinking water induces in contrast a robust and consistent depletion of mouse fecal bacteria, as soon as 4 days of treatment, and is associated with an increase in fecal moisture content. Extending exposure to antibiotics beyond 7 days does not improve total bacteria depletion efficiency and promotes fungal overgrowth. We show in addition that all tested protocols impact neither gut microbiota recolonization efficiency, 1 or 2 weeks after the stop of antibiotics, nor mice body composition after 1 week of treatment. Conclusions Our study provides key experimental data and highlights important parameters to consider before selecting an appropriate protocol for antibiotic-mediated depletion of gut bacteria, in order to optimize the accuracy and the reproducibility of results and to facilitate comparison between studies.

Abstract Undernutrition is a global health issue leading to 1 out 5 all deaths in children under 5 years. Undernutrition is often associated with environmental enteric dysfunction (EED), a syndrome associated with increased intestinal permeability and gut inflammation. We aimed to develop a novel murine model of undernutrition with these EED features. Post-weaning mice were fed with low-protein diet (LP) alone or combined with a gastrointestinal insult trigger (indomethacin or liposaccharides). Growth, intestinal permeability and inflammation were assessed. LP diet induced stunting and wasting in post-weaning mice but did not impact gut barrier. We therefore combined LP diet with a single administration of indomethacin or liposaccharides (LPS). Indomethacin increased fecal calprotectin production while LPS did not. To amplify indomethacin effects, we investigated its repeated administration in addition to LP diet and mice exhibited stunting and wasting with intestinal hyperpermeability and gut inflammation. The combination of 3-weeks LP diet with repeated oral indomethacin administration induced wasting, stunting and gut barrier dysfunction as observed in undernourished children with EED. As noninvasive methods for investigating gut function in undernourished children are scarce, the present pre-clinical model provides an affordable tool to attempt to elucidate pathophysiological processes involved in EED and to identify novel therapeutic strategies.

Summary: Dysregulation of gut-brain axis seems to play a key role in anorexia nervosa (AN) pathophysiology. Central alterations of hypothalamic–pituitary–adrenal axis, neurotransmission, food intake regulation, and peripheral alterations of gut barrier, gut microbiota, immune system, have been reported in AN. Potential beneficial effects of physical activity on gut-brain axis have been observed during refeeding in AN. As nutritional support, psychotherapy, anxiolytics, antidepressants, programmed physical activity needs to be considered as a novel therapeutic tool in AN management. In the future, combined strategies of gut-brain modulations should be assessed in AN, including other promising candidates, probiotics, glutamine and omega-3 fatty acids. Keywords: Physical activity, Anorexia nervosa, Microbiota, Gut, Brain

Summary: Anorexia nervosa is an eating disorder characterized by a severe malnutrition, an intense fear of gaining weight and a disturbed self-body image. Anorexia is conventionally considered as a multifactorial disease depending on biological, psychological and socio-cultural factors. Among the different biological factors involved in this eating disorder, the gut microbiota has recently gained a lot of attention. Indeed, the identification of an intestinal microbiota dysbiosis in individuals with anorexia has opened new and promising lines of research. These researches focus in particular on the role of intestinal micro-organisms in the functional gastrointestinal disorders associated with Anorexia, in anxiety and depression-related disorders as well as in the regulation of eating behavior. This review aims to present the current knowledge about the putative role of the gut microbiota in the pathogenesis, course and treatment of Anorexia nervosa. Keywords: Microbiota, Anorexia nervosa, Eating disorders, Functional gastrointestinal disorders, Anxiety, Depression

Abstract Background We evaluated the performance of a clinical algorithm (Expali™), combining two or more positive answers to SCOFF questionnaire with Body Mass Index (BMI), to identify four Broad Categories of eating disorders (ED) derived from DSM-5. Methods The clinical algorithm (Expali™) was developed from 104 combinations of BMI levels and answers to five SCOFF questions with at least two positive answers. Two senior ED physicians allocated each combination to one of the four Broad Categories of ED derived from DSM-5: restrictive disorder, bulimic disorder, hyperphagic disorder and other unspecified ED diagnosed by ED clinicians. The performance of Expali™ was evaluated on data from 206 patients with ED. Sensitivity, specificity values and Youden index were calculated for each category. Results The 206 patients were diagnosed as follows: 31.5% restrictive disorder, 18.9% bulimic disorder, 40.8% hyperphagic disorder and 8.8% other ED. The sensitivity of Expali™ for restrictive, bulimic, hyperphagic and other unspecified ED were respectively: 76.9, 69.2, 79.7 and 16.7%. The Youden index was respectively 0.73, 0.57, 0.67 and 0.07. Conclusions In a SCOFF-positive ED population (at least two positive answers), the clinical algorithm Expali™ demonstrated good suitability by correctly classifying three of the four Broad Categories of eating disorders (restrictive, bulimic and hyperphagic disorder). It could be useful both to healthcare professionals and the general population to enable earlier detection and treatment of ED and to improve patient outcomes.

BackgroundGastric necrosis following acute gastric dilatation is rare but more common in females with eating disorders, such as anorexia nervosa or bulimia, during which patients often alternate restriction and binge eating behaviors.Case PresentationA 37-year old female patient with a history of 15 years of bulimia nervosa was admitted to the emergency department 24 h after binge eating. Abdominal Computed Tomography imaging showed major gastric distension reaching the pelvis and compressing the digestive organs. Total gastrectomy was required because of gastric necrosis. The patient reported significant reduction in bulimic symptoms after gastrectomy.ConclusionWe discuss here the possible mechanisms underlying this recovery, including changes in gut-derived factors that could mediate eating behavior changes.

Obesity, a worldwide health concern with a constantly rising prevalence, is a multifactorial chronic disease associated with a wide range of physiological disruptions, including energy imbalance, central appetite and food reward dysregulation, and hormonal alterations and gut dysbiosis. The gut microbiome is a well-recognized factor in the pathophysiology of obesity, and its influence on host physiology has been extensively investigated over the last decade. This review highlights the mechanisms by which gut dysbiosis can contribute to the pathophysiology of obesity. In particular, we discuss gut microbiota’s contribution to host energy homeostatic changes, low-grade inflammation, and regulation of fat deposition and bile acid metabolism via bacterial metabolites, such as short-chain fatty acids, and bacterial components, such as lipopolysaccharides, among others. Finally, therapeutic strategies based on next-generation probiotics aiming to re-shape the intestinal microbiota and reverse metabolic alterations associated with obesity are described.

Abstract Restrictive anorexia nervosa is associated with reduced eating and severe body weight loss leading to a cachectic state. Hypothalamus plays a major role in the regulation of food intake and energy homeostasis. In the present study, alterations of hypothalamic proteome and particularly of proteins involved in energy and mitochondrial metabolism have been observed in female activity-based anorexia (ABA) mice that exhibited a reduced food intake and a severe weight loss. In the hypothalamus, mitochondrial dynamic was also modified during ABA with an increase of fission without modification of fusion. In addition, increased dynamin-1, and LC3II/LC3I ratio signed an activation of autophagy while protein synthesis was increased. In conclusion, proteomic analysis revealed an adaptive hypothalamic protein response in ABA female mice with both altered mitochondrial response and activated autophagy.

Abstract Background Enterococcus faecalis, generally considered as a saprophytic bowel commensal, has recently emerged as an important nosocomial pathogen causing severe urinary tract infections, surgical wound infections, bacteremia, and bacterial endocarditis. This bacterium is capable of forming biofilms on various surfaces and its high level of antibiotic resistance contributes to its pathogenicity. The aim of this study was to evaluate the effect on E. faecalis, of Substance P (SP), an antimicrobial peptide that is produced in the gut and skin. Results We found that SP did not have antibacterial activity against E. faecalis V583 (MIC >1000 µg/ml). Conversely, SP stimulated aggregation, hydrophobicity, lactic acid and tyramine production in this bacterium. The cytotoxicity and bacterial translocation were also accelerated when E. faecalis V583 were pretreated with SP before infection of intestinal Caco-2/TC7 cells. Conclusion SP can modulate the physiology of E. faecalis. Extensive studies are now needed to screen within the human microbiota which bacteria are responsive to host molecules, and to identify their sensors.

Objective: To compare the prevalence of anxiety and depression states and eating disorders (EDs) between patients with irritable bowel syndrome (IBS) and healthy volunteers without IBS.Methods: IBS patients according to Rome III criteria referred to our tertiary care center for therapeutic management and matched volunteers without IBS were prospectively included. EDs were screened by Sick, Control, One stone, Fat, Food—French version (SCOFF-F) questionnaire. IBS symptom severity (IBS symptom severity score), stool consistency (Bristol stool scale), anxiety and depression levels (Hospital Anxiety and Depression scale), and quality of life (validated Gastrointestinal Quality of Life Index) were assessed by validated self-questionnaires.Results: IBS (228) patients and healthy volunteers (228) were included. Mean age was 42.5 ± 13.9 years with mainly women (76.7%). Among IBS patients, 25.4% had positive SCOFF-F compared to 21.1% of volunteers. IBS patients more frequently had a lower body mass index (BMI) than volunteers (p < 0.0001). IBS patients with ED had poorer quality of life and more stressful life events (p = 0.02) than IBS patients without ED. The prevalence of anxiety and depression was significantly higher in IBS patients with ED than in volunteers without ED, respectively (19.0% vs 1.9%, p=0.00, and 60.3% vs 19.7%, p < 0.0001).Conclusions: The prevalence of ED assessed with positive SCOFF-F questionnaire was not significantly different between IBS patients and healthy volunteers. The combination of IBS and ED was associated with higher levels of anxiety or depression and poorer quality of life.

Altered signaling between gut bacteria and their host has recently been implicated in the pathophysiology of eating disorders, whereas the enterobacterial caseinolytic protease B (ClpB) may play a key role as an antigen mimetic of α-melanocyte-stimulating hormone, an anorexigenic neuropeptide. Here, we studied whether ClpB production by gut bacteria can be modified by chronic food restriction and female sex, two major risk factors for the development of eating disorders. We found that food restriction increased ClpB DNA in feces and ClpB protein in plasma in both male and female rats, whereas females displayed elevated basal ClpB protein levels in the lower gut and plasma as well as increased ClpB-reactive immunoglobulins (Ig)M and IgG. In contrast, direct application of estradiol in E. coli cultures decreased ClpB concentrations in bacteria, while testosterone had no effect. Thus, these data support a mechanistic link between host-dependent risk factors of eating disorders and the enterobacterial ClpB protein production.

In today’s Integrated Circuit (IC) production chains, a designer’s valuable Intellectual Property (IP) is transparent to diverse stakeholders and thus inevitably prone to piracy. To protect against this threat, numerous defenses based on the obfuscation of a circuit’s control path, i.e. Finite State Machine (FSM), have been proposed and are commonly believed to be secure. However, the security of these sequential obfuscation schemes is doubtful since realistic capabilities of reverse engineering and subsequent manipulation are commonly neglected in the security analysis. The contribution of our work is threefold: First, we demonstrate how high-level control path information can be automatically extracted from third-party, gate-level netlists. To this end, we extend state-of-the-art reverse engineering algorithms to deal with Field Programmable Gate Array (FPGA) gate-level netlists equipped with FSM obfuscation. Second, on the basis of realistic reverse engineering capabilities we carefully review the security of state-of-the-art FSM obfuscation schemes. We reveal several generic strategies that bypass allegedly secure FSM obfuscation schemes and we practically demonstrate our attacks for a several of hardware designs, including cryptographic IP cores. Third, we present the design and implementation of Hardware Nanomites, a novel obfuscation scheme based on partial dynamic reconfiguration that generically mitigates existing algorithmic reverse engineering.

BackgroundHealthcare students are future health care providers and serve as role models and coaches to enhance behaviors for healthy lifestyles. However healthcare students face multiple stressors that could lead to adopting risk behaviors.ObjectivesTo assess the changes in health risk factors among healthcare students between 2007 and 2015, and to identify specific health behaviors based on the curriculum in a population of healthcare students.MethodsTwo cross sectionnal studies were conducted in 2007 and 2015 among nursing, medical, pharmacy, and physiotherapy students (Rouen, France). During compulsory courses and examination sessions students filled self-administered questionnaires on socio-demographic characteristics and behavior as: tobacco smoking, alcohol consumption, cannabis consumption, eating disorders, regular practice of sport, perceived health, stress and use of psychotropic drugs.Results2,605 healthcare students were included (1,326 in 2007 and 1,279 in 2015), comprising 1,225 medical students (47.0%), 738 nursing students (28.3%), 362 pharmacy students (13.9%), and 280 physiotherapy students (10.8%). Between 2007 and 2015, occasional binge drinking and regular practice of sport increased significantly among healthcare students, respectively AOR = 1.48 CI95% (1.20-1.83) and AOR = 1.33 CI95% (1.11-1.60), regular cannabis consumption decreased significantly, AOR = 0.32 CI95% (0.19-0.54). There was no change in smoking or overweight/obese. There was a higher risk of frequent binge drinking and a lower risk of tobacco smoking in all curricula than in nursing students. Medical students practiced sport on a more regular basis, were less overweight/obese, had fewer eating disorders than nursing students.ConclusionOur findings demonstrate a stable frequency of classic behaviors as smoking but a worsening of emerging behaviors as binge drinking among healthcare students between 2007 and 2015. Health behaviors differed according to healthcare curricula and nursing students demonstrated higher risks. As health behaviors are positively related to favorable attitudes towards preventive counseling, therefore healthcare students should receive training in preventive counseling and develop healthy lifestyles targeted according to the health curriculum.

BACKGROUND AND AIMS:Body composition assessment is often used in clinical practice for nutritional evaluation and monitoring. The standard method, dual-energy X-ray absorptiometry (DXA), is hardly feasible in routine clinical practice contrary to Bioelectrical Impedance Analysis (BIA) method. We thus aimed to compare body composition assessment by DXA and BIA according to the body mass index (BMI) in a large cohort. METHODS:Retrospectively, we analysed DXA and BIA measures in patients followed in a Nutrition Unit from 2010 to 2016. Body composition was assessed under standardized conditions in the morning, after a fasting period of 12 h, by DXA (Lunar Prodigy Advance) and BIA (Bodystat QuadScan 4000, Manufacturer's equation). Bland-Altman test was performed for each class of BMI (kg/m2) and fat mass and fat free mass values were compared using Kruskal-Wallis test. Pearson correlations were also performed and the concordance coefficient of Lin was calculated. RESULTS:Whatever the BMI, BIA and DXA methods reported higher concordance for values of FM than FFM. Body composition values were very closed for patients with BMI between 16 and 18,5 (difference < 1kg). For BMI > 18,5 and BMI < 40, BIA overestimated fat free mass from 3,38 to 8,28 kg, and underestimated fat mass from 2,51 to 5,67 kg compared with DXA method. For BMI ≥ 40, differences vary with BMI. For BMI < 16, BIA underestimated fat free mass by 2,25 kg, and overestimated fat mass by 2,57 kg. However, limits of agreement were very large either for FM and FFM values, irrespective of BMI. CONCLUSION:The small bias, particularly in patients with BMI between 16 and 18, suggests that BIA and DXA methods are interchangeable at a population level. However, concordance between BIA and DXA methods at the individual level is lacking, irrespective of BMI.

Low bone mineral density (BMD) is a frequent complication in anorexia nervosa (AN). There are controversial points of views regarding the restoration of bone mineralization after recovery in AN. We aimed to assess changes of BMD at 3 years in patients with AN and to explore the relationships between body composition, physical activity, and BMD. Patients with AN were included from 2009 to 2011 in a first visit (T0) with evaluation of weight, height, body mass index (BMI), body composition [fat mass (FM) and fat-free mass], and BMD. Those who had low BMD, either osteoporosis or osteopenia, were admitted in a second visit (T1) to carry out a new bone densitometry examination and body composition; they were also asked for their physical activity. At T0, our study involved 160 patients. Low BMD was observed in 53.6% of them and significant factors associated with demineralization were lower BMIs (16.5 ± 2.1 vs 17.3 ± 2.3 kg/m2, p = 0.01) and higher duration of AN (11.4 ± 10.5 vs 6.4 ± 6.5 years, p = 0.001). At 3 years follow-up (T1), 42 patients were involved and no significant changes in BMD were observed despite body weight increase (3.8 ± 6.1 kg). Interestingly, FM gain was a significant factor associated with BMD improvement at follow-up (8.0 ± 9.1 vs 3.0 ± 3.5 kg, p = 0.02). Our findings suggest that the restoration of normal bone values is not related to the increase of body weight, at least after 3 years. FM seems to play an important role in the pathophysiological mechanism of osteoporosis and osteopenia in AN.

Use of new generation probiotics may become an integral part of the prevention and treatment strategies of obesity. The aim of the present study was to test the efficacy of a potential probiotic strain of lactic bacteria Hafnia alvei (H. alvei) HA4597™, in a mouse model of obesity characterized by both hyperphagia and diet-induced adiposity. For this purpose, 10-week-old high-fat-diet (HFD)-fed hyperphagic ob/ob male mice received a daily treatment with 1.4 × 1010 CFU of H. alvei for 38 days. Effects of H. alvei were compared to those of a lipase inhibitor orlistat (80 mg/kg daily) and a vehicle (NaCl 0.9%) in HFD-fed ob/ob mice. A control untreated group of ob/ob mice received the standard diet throughout the experiment. The vehicle-treated HFD group displayed increased food intake, worsening of adiposity, and glycemia. Treatment with H. alvei was accompanied by decreased body weight and fat-mass gain along with reduced food intake to the level of the standard-diet-fed mice. At the end of the experiment, the group treated with H. alvei showed a decrease of glycemia, plasma total cholesterol, and alanine aminotransferase. The orlistat-treated mice showed a lower rate of body weight gain but were hyperphagic and hyperglycemic. These results demonstrate the beneficial anti-obesity and metabolic effects of H. alvei HA4597™ in mice with obesity resulting from hyperphagia and diet-induced adiposity.

Background and aims: Cancer chemotherapy is commonly accompanied by mucositis, anorexia, weight loss and anxiety independently from cancer-induced anorexia-cachexia, further aggravating clinical outcome. Ghrelin is a peptide hormone produced in gastric mucosa that reaches the brain to stimulate appetite. In plasma, ghrelin is protected from degradation by ghrelin-reactive immunoglobulins (Ig). To analyze possible involvement of ghrelin in the chemotherapy-induced anorexia and anxiety, gastric ghrelin expression, plasma levels of ghrelin and ghrelin-reactive IgG were studied in rats treated with methotrexate (MTX).Methods: Rats received MTX (2.5 mg/kg, S.C.) for three consecutive days and were killed 3 days later, at the peak of anorexia and weight loss. Control rats received phosphate-buffered saline. Preproghrelin mRNA expression in the stomach was analyzed by in situ hybridization. Plasma levels of ghrelin and ghrelin-reactive IgG were measured by immunoenzymatic assays and IgG affinity kinetics by surface plasmon resonance. Anxiety- and depression-like behaviors in MTX-treated anorectic and in control rats were evaluated in the elevated plus-maze and the forced-swim test, respectively.Results: In MTX-treated anorectic rats the number of preproghrelin mRNA-producing cells was found increased (by 51.3%, p

BACKGROUND:Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu2+ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients. METHODS:This retrospective study was conducted at a single center (University Hospital of Clermont-Ferrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb-IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples. RESULTS:Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p

BACKGROUND: Magnetic resonance colonography (MRC) has been developed to assess inflammatory bowel diseases. We aimed to assess the feasibility of MRC in rats with TNBS-induced chronic colitis and to confront imaging results with fibrosis and stenosing features of the model. MATERIALS AND METHODS: Chronic colitis was induced in 12 rats by weekly intra-rectal injection of increasing doses of TNBS for 6 weeks, while 8 control rats received the vehicle. At week 7, MRC was performed. Fibrosis scores were assessed and fibrosis mediators measured. RESULTS: Chronic colitis was associated with significant body weight loss (p