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Admixture-like plot displaying membership probabilities for NCWS and continental population clusters computed by DAPC. Probabilities belonging to the EAS, EUR, and AFR clusters are, respectively, displayed in green, red, and blue. (PDF 74Â kb)

Flowchart describing schematic representation of the implemented research approach detailing steps for NCWS sample selection and applied population genetics analytical workflow. (PDF 24Â kb)

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in Western countries. Although the aberrant expression of several microRNAs (oncomiRs) is associated with CRC progression, the molecular mechanisms of this phenomenon are still under investigation. Here we show that miR-101 expression is differentially impaired in CRC specimens, depending on tumour grade. miR-101 re-expression suppresses cell growth in 3D, hypoxic survival and invasive potential in CRC cells showing low levels of miR-101. Additionally, we provide molecular evidence of a bidirectional regulatory mechanism between miR-101 expression and important CRC pro-malignant features, such as inflammation, activation of the Wnt/β-catenin signalling pathway and epithelial–mesenchymal transition (EMT). We then propose that up-regulated miR-101 may function as a tumour suppressor in CRC and that its pharmacological restoration might hamper the aggressive ehaviour of CRC in vivo. MiR-101 expression may also represent a cancer biomarker for CRC diagnosis and prognosis.

BACKGROUND: Cannabinoid (CB) receptors have been located in brain areas involved in the triggering of TLESRs as well as in the nodose ganglion from which vagal afferents emanate. The distribution of CB(1) receptors has been investigated in the human gastrointestinal mucosa, as expression of inflammatory process. AIM: To evaluate the CB(1) expression in oesophageal mucosa. METHODS: A total of 87 consecutive subjects were enrolled: 10 controls, 39 NERD and 38 erosive oesophagitis. Eight specimens were taken from macroscopically normal mucosa. Five were processed by haematoxylin-eosin, MIB1/CB(1) evaluation and three for the RNA and proteins extraction. RESULTS: The mean MIB1-LI value was 31% and 22% in NERD and ERD patients, respectively, compared to 68% in the healthy subjects. Mean CB(1)mRNA/GUSB mRNA value of the controls was 0.66, while in GERD patients, it was 0.28. In NERD and ERD, the mean values of CB(1)/GUSB were 0.38 and 0.17, respectively, with highly significant differences between the NERD vs. ERD groups. Semi-quantitative analysis of CB(1) expression, performed with WB, shows in NERD patients a higher CB(1) receptor expression than ERD patients. CONCLUSIONS: With this study, we showed for the first time the presence of CB(1) receptors in the human oesophageal epithelium.

The distinction between active inflammation and fibrosis of the bowel wall is essential for therapeutic decisions in stricturing Crohn's disease. We aimed to assess whether real-time elastography (RTE) with strain ratio measurement could be useful in differentiating fibrotic from inflamed bowel strictures and to evaluate the possible relationship between US techniques and the histology of the stenotic bowel wall.Bowel ultrasonography (including RTE, color-Doppler and CEUS examination) was prospectively evaluated in 26 patients with symptomatic stricturing Crohn's disease, before surgery. RTE was adopted to evaluate bowel stiffness: five loops of 20 RTE frames were recorded for each stenotic segment and the mean strain ratio (MSR) was obtained. Histology scoring systems both for inflammation and fibrosis were established for surgical specimens.No significant correlation was found between MSR and fibrosis score (MSR detection was not able to distinguish fibrotic from inflammatory tissue in our selected population. This result could be influenced by the presence of the superimposed inflammation. Larger cohort of patients, further analysis with shear wave elastography, and validated histopathology classification systems for fibrosis and inflammation are necessary to assess if intestinal fibrosis could be reliably detected on the basis of bowel elastic properties.la distinzione tra infiammazione attiva e fibrosi nella parete intestinale è essenziale nel proceso decisionale della terapia nella malattia di Crohn stenosante. Lo scopo del nostro studio era di stabilire se l’elastografia real-time (RTE) con la misurazione dello strain ratio potesse essere utile nel differenziare il tessuto fibrotico da quello infiammatorio nella parete intestinale stenotica, e di valutare la presenza di correlazioni tra le tecniche ecografiche di studio delle anse intestinali e le caratteristiche istologiche dei segmenti analizzati.Lo studio ecografico delle anse intestinali che comprendeva anche RTE, valutazione color-Doppler e CEUS, è stato eseguito in maniera prospettica in 26 pazienti con malattia di Crohn stenosante sintomatica, prima dell’ intervento chirurgico resettivo. La RTE è stata utilizzata per valutare la rigidità della parete intestinale: 5 filmati di 20 frames di elastografia sono stati registrati per ogni segmento stenotico, per ogni frame è stato calcolato lo strain ratio e quindi ne è stata ottenuta la media (MSR). E’ stato poi stabilito uno score istologico per l’ infiammazione e la fibrosi per i pezzi operatori analizzati.non è stata rilevata alcuna correlazione significativa tra MSR e score istologico della fibrosi (P = 0877). Il Color-doppler correlava significativamente con lo spessore di parete e l’ispessimento della sottomucosa (P = 0006 e P = 0032, rispettivamente). Non è stata trovata una correlazione significativa tra il numero di vasi rilevato sul pezzo istologico e gli score color-Doppler e CEUS (P = 0170 e P = 0302, rispettivamente).il calcolo del MSR non si è rivelato un parametro efficace nel distinguere tra tessuto fibrotico ed infiammatorio nella nostra popolazione. Questo risultato è influenzato da vari fattori, tra cui probabilmente la compresenza di infiammazione. Coorti di pazienti più ampie, ulteriori analisi con l’ausilio eventualmente dell’ elastografia shear-wave, e sistemi di classificazione istopatologici validati sia per la fibrosi che per l’infiammazione, risultano necessari per stabilire se la fibrosi intestinale possa essere rilevata in maniera affidabile sulla base delle proprietà elastiche della parete intestinale.

Objectives Higher prevalence of psychiatric disorders, such as anxiety and depression, has been found in people with Crohn's disease and Ulcerative Colitis compared to the general population. Nowadays, international guidelines advocate psychotherapy and psycho-pharmacological treatments as playing an important role in IBD care. The main goal of this systematic literature review was summarize the evidence on the utilization and effectiveness of treatments for depression and anxiety in persons with IBD. Methods A systematic literature review was conducted using three different electronic databases: MEDLINE, PsychINFO, and EMBASE to identify studies reporting the prevalence and efficacy of psycho-pharmacological and psychotherapeutic treatments for IBD. A quality appraisal was conducted using several scales as appropriate for each study design. A narrative synthesis was also performed. Results Forty-three studies were included. Although a high rate of psychoactive drug use was found in people with IBD, a low proportion of IBD patients have access to psychiatric referral. 1/3 of the studies found that psychotherapy was effective for improving the quality of life, perception of stress, anxiety and depression as well as disease. Antidepressants proved effective in reducing disease activity, gastrointestinal symptoms, anxiety and depression. Conclusion Our results suggest that psychiatric treatment should be implemented in IBD care. However, further studies are needed to confirm the findings of our systematic review.

Ulcerative colitis (UC) is a chronic inflammatory disease which involves the colonic mucosa continuously starting from the rectum and progressively involving the entire colon. Its etiology is still unknown, although numerous studies have clarified the inflammatory mechanisms involved in the pathogenesis, allowing the development of new targeted drugs. Correct medical treatment requires the evaluation of disease extension, activity and behavior [1]. The Montreal classification allows extent to be defined into three subgroups: proctitis (when the inflammation is limited to the rectum), left-sided colitis (distal to the splenic flexure), and extensive or pancolitis (proximal to the splenic flexure) [2]. Drug formulation is chosen based on the disease extent: suppositories for proctitis, enemas for left-sided colitis and tablets for extensive colitis. Furthermore, patients with extensive colitis have a higher risk of colectomy or of developing colorectal...

Introduction: Beclomethasone dipropionate (BDP) is a second-generation corticosteroid that uses novel drug technologies to ensure colonic targeting and potentially reducing systemic corticosteroid concentrations. It is approved for treatment of patients with mild-to-moderate ulcerative colitis (UC) who do not respond to mesalazine. The gut-selective mechanism of action has the potential to improve the safety profile of BDP compared with other conventional corticosteroids. Areas covered: We reviewed the mechanism of action, efficacy, and safety of BDP in the treatment of UC. The positioning of BDP in management algorithms is also discussed. Expert opinion: The highly selective mechanism of action of BDP restricts the steroid-related side effects. BDP is efficacious in the treatment of active UC. Topical formulation is the first choice in distal UC, while oral formulation is used in patients with an extensive involvement of the colon. The rates of adverse events (AE), serious AEs, and steroid-related side-effects are similar to placebo and mesalamine and slightly inferior to traditional corticosteroids.

International audience; Background and Aims: Gut microbiota is involved in many physiological functions and its imbalance is associated with several diseases, particularly with inflammatory bowel diseases. Mucosa-associated microbiota could have a key role in induction of host immunity and in inflammatory process. Although the role of fungi has been suggested in inflammatory disease pathogenesis, the fungal microbiota has not yet been deeply explored. Here we analysed the bacterial and fungal composition of the mucosa-associated microbiota of Crohn's disease patients and healthy subjects.Methods: Our prospective, observational study evaluated bacterial and fungal composition of mucosa-associated microbiota of 23 Crohn's disease patients [16 in flare, 7 in remission] and 10 healthy subjects, using 16S [MiSeq] and ITS2 [pyrosequencing] sequencing, respectively. Global fungal load was assessed by real time quantitative polymerase chain reaction. Results: Bacterial microbiota in Crohn's disease patients was characterised by a restriction in biodiversity. with an increase of Proteobacteria and Fusobacteria. Global fungus load was significantly increased in Crohn's disease flare compared with healthy subjects [p < 0.05]. In both groups, the colonic mucosa-associated fungal microbiota was dominated by Basidiomycota and Ascomycota phyla. Cystofilobasidiaceae family and Candida glabrata species were overrepresented in Crohn's disease. Saccharomyces cerevisiae and Filobasidium uniguttulatum species were associated with non-inflamed mucosa, whereas Xylariales order was associated with inflamed mucosa.Conclusions: Our study confirms the alteration of the bacterial microbiota and is the first demonstration of the existence of an altered fungal microbiota in Crohn's disease patients, suggesting that fungi may play a role in pathogenesis.

Background & Aims: High fecal levels of calprotectin indicate mucosal inflammation and have been shown to predict relapse in patients with ulcerative colitis (UC). Eicosapentaenoic acid (EPA), the major component of n-3 fish oil, has anti-inflammatory properties in patients with chronic inflammatory disorders. We performed a placebo-controlled trial of patients with UC at risk of relapse to determine the ability of the free fatty acid form of EPA (EPA-FFA) to reduce intestinal inflammation, using fecal level of calprotectin as a marker. Methods: From June 2014 to May 2016, 60 patients with UC with a partial Mayo score < 2 and fecal calprotectin ≥150 μg/g, in stable therapy for at least the 3 previous months, were randomly assigned to groups (1:1) given either EPA-FFA (500 mg, twice daily) or placebo for 6 months. A colonoscopy was performed at baseline. Clinical assessments and measurements of fecal calprotectin were made at baseline, at study months 3 and 6, or the time of clinical relapse. Patients with a relapse of UC underwent a second colonoscopy. The primary end point was a 100-point reduction in fecal levels of calprotectin at 6 months from the baseline value; the secondary end point was maintenance of clinical remission at 6 months. Results: The primary end point was achieved by 19 of 30 patients (63.3%) in the EPA-FFA group vs 4 of 30 patients (13.3%) in the placebo group (odds ratio, 12.0; 95% CI, 3.12–46.24; P

none 15 no Background: Non-celiac wheat sensitivity is an emerging wheat-related syndrome showing peak prevalence in Western populations. Recent studies hypothesize that new gliadin alleles introduced in the human diet by replacement of ancient wheat with modern varieties can prompt immune responses mediated by the CXCR3-chemokine axis potentially underlying such pathogenic inflammation. This cultural shift may also explain disease epidemiology, having turned European-specific adaptive alleles previously targeted by natural selection into disadvantageous ones. Methods: To explore this evolutionary scenario, we performed ultra-deep sequencing of genes pivotal in the CXCR3-inflammatory pathway on individuals diagnosed for non-celiac wheat sensitivity and we applied anthropological evolutionary genetics methods to sequence data from worldwide populations to investigate the genetic legacy of natural selection on these loci. Results: Our results indicate that balancing selection has maintained two divergent CXCL10/CXCL11 haplotypes in Europeans, one responsible for boosting inflammatory reactions and another for encoding moderate chemokine expression. Conclusions: This led to considerably higher occurrence of the former haplotype in Western people than in Africans and East Asians, suggesting that they might be more prone to side effects related to the consumption of modern wheat varieties. Accordingly, this study contributed to shed new light on some of the mechanisms potentially involved in the disease etiology and on the evolutionary bases of its present-day epidemiological patterns. Moreover, overrepresentation of disease homozygotes for the dis-adaptive haplotype plausibly accounts for their even more enhanced CXCR3-axis expression and for their further increase in disease risk, representing a promising finding to be validated by larger follow-up studies. open Sazzini, Marco; De Fanti, Sara; Cherubini, Anna; Quagliariello, Andrea; Profiti, Giuseppe; Martelli, Pier Luigi; Casadio, Rita; Ricci, Chiara; Campieri, Massimo; Lanzini, Alberto; Volta, Umberto; Caio, Giacomo; Franceschi, Claudio; Spisni, Enzo; Luiselli, Donata Sazzini, Marco; De Fanti, Sara; Cherubini, Anna; Quagliariello, Andrea; Profiti, Giuseppe; Martelli, Pier Luigi; Casadio, Rita; Ricci, Chiara; Campieri, Massimo; Lanzini, Alberto; Volta, Umberto; Caio, Giacomo; Franceschi, Claudio; Spisni, Enzo; Luiselli, Donata