Inhibition of intestinal inflammation and fibrosis by Scutellaria Baicalensis georgi and Boswellia serrata in human epithelial cells and fibroblasts.

Objective And Rationale: Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, manifests with chronic intestinal inflammation and frequent sequential fibrosis. Current pharmacological therapies may show harmful side effects and are not useful for prevention or resolution of fibrosis. Thus, the use of alternative therapies is emerging as a novel useful approach.

PARP1 inactivation increases regulatory T / Th17 cell proportion in intestinal inflammation. Role of HMGB1.

Inflammatory bowel diseases (IBD) are chronic relapsing disorders with increasing prevalence. Knowledge gaps still limit the possibility to develop more specific and effective therapies. Using a dextran sodium sulfate colitis mouse model, we found that inflammation increased the total number and altered the frequencies of leukocytes within colon mesenteric lymph nodes (cMLNs).

Characterization of patient-derived intestinal organoids for modelling fibrosis in Inflammatory Bowel Disease.

Background And Aims: Intestinal fibrosis is a common complication of Inflammatory Bowel Disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), but the precise mechanism by which it occurs is incompletely understood hampering the development of effective therapeutic strategies. Here, we aimed at inducing and characterizing an inflammation-mediated fibrosis in patient-derived organoids (PDOs) issued from crypts isolated from colonic mucosal biopsies of IBD pediatric patients and age matched-control subjects (CTRLs).

Methods: Inflammatory-driven fibrosis was induced by exposing CTRL-, CD- and UC-PDOs to the pro-inflammatory cytokine TNF-α for one day, followed by a co-treatment with TNF-α and TGF-β1 for three days.

Characterization of Early and Late Damage in a Mouse Model of Pelvic Radiation Disease.

Pelvic radiation disease (PRD), a frequent side effect in patients with abdominal/pelvic cancers treated with radiotherapy, remains an unmet medical need. Currently available preclinical models have limited applications for the investigation of PRD pathogenesis and possible therapeutic strategies. In order to select the most effective irradiation protocol for PRD induction in mice, we evaluated the efficacy of three different locally and fractionated X-ray exposures.

PARP1 Activation Induces HMGB1 Secretion Promoting Intestinal Inflammation in Mice and Human Intestinal Organoids.

Extracellular High-mobility group box 1 (HMGB1) contributes to the pathogenesis of inflammatory disorders, including inflammatory bowel diseases (IBD). Poly (ADP-ribose) polymerase 1 (PARP1) has been recently reported to promote HMGB1 acetylation and its secretion outside cells. In this study, the relationship between HMGB1 and PARP1 in controlling intestinal inflammation was explored.

ZNF281 Promotes Colon Fibroblast Activation in TGFβ1-Induced Gut Fibrosis.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract. Chronic inflammation is the main factor leading to intestinal fibrosis, resulting in recurrent stenosis, especially in CD patients. Currently, the underlying molecular mechanisms of fibrosis are still unclear.

Proteomic Analysis Identifies Three Reliable Biomarkers of Intestinal Inflammation in the Stools of Patients With Inflammatory Bowel Disease.

Background: Faecal biomarkers have emerged as important tools in managing of inflammatory bowel disease [IBD], which includes Crohn's disease [CD] and ulcerative colitis [UC].

Aim: To identify new biomarkers of gut inflammation in the stools of IBD patients using a proteomic approach.

Methods: Proteomic analysis of stools was performed in patients with both active CD and CD in remission and in controls by 2-DIGE and MALDI-TOF/TOF MS.

Innovative method to grow the probiotic Lactobacillus reuteri in the omega3-rich microalga Isochrysis galbana.

Microalgae are natural sources of valuable bioactive compounds, such as polyunsaturated fatty acids (PUFAs), that show antioxidant, anti-inflammatory, anticancer and antimicrobial activities. The marine microalga Isochrysis galbana (I. galbana) is extremely rich in ω3 PUFAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Colonic inflammation accelerates the progression of liver disease: A protective role of dipotassium glycyrrhizate.

Background: The incidence of non-alcoholic fatty liver disease (NAFLD) and its more severe and progressive form, non-alcoholic steatohepatitis (NASH) is increasing worldwide. Gut inflammation seems to concur to the pathogenesis of NASH. No drugs are currently approved for NASH treatment.

Fecal High-Mobility Group Box 1 as a Marker of Early Stage of Necrotizing Enterocolitis in Preterm Neonates.

An early diagnosis of necrotizing enterocolitis (NEC), a major gastrointestinal emergency in preterm newborns, is crucial to improve diagnostic approach and prognosis. We evaluated whether fecal high-mobility group box protein 1 (HMGB1) may early identify preterms at risk of developing NEC. A case-control study including neonates admitted at the Neonatal Intensive Care Unit (NICU) of the Sapienza University Hospital "Umberto I" in Rome, from July 2015 to December 2016.

Intestinal Inflammation Alters the Expression of Hepatic Bile Acid Receptors Causing Liver Impairment.

Objectives: The gut-liver axis has been recently investigated in depth in relation to intestinal and hepatic diseases. Key actors are bile acid (BA) receptors, as farnesoid-X-receptor (FXR), pregnane-X-receptor (PXR), and G-protein-coupled-receptor (GPCR; TGR5), that control a broad range of metabolic processes as well as inflammation and fibrosis. The present study aims to investigate the impact of intestinal inflammation on liver health with a focus on FXR, PXR, and TGR5 expression.

Functional analysis of gut microbiota and immunoinflammation in children with autism spectrum disorders.

Background And Aims: Recent evidence implicates gut microbiota (GM) and immune alterations in autism spectrum disorders (ASD). We assess GM profile and peripheral levels of immunological, neuronal and bacterial molecules in ASD children and controls. Alarmin HMGB1 was explored as a non-invasive biomarker to monitor gastrointestinal (GI) symptoms.

A structure-based mechanism of cisplatin resistance mediated by glutathione transferase P1-1.

Cisplatin [diamminedichloroplatinum(II) (-DDP)] is one of the most successful anticancer agents effective against a wide range of solid tumors. However, its use is restricted by side effects and/or by intrinsic or acquired drug resistance. Here, we probed the role of glutathione transferase (GST) P1-1, an antiapoptotic protein often overexpressed in drug-resistant tumors, as a -DDP-binding protein.

Dipotassium Glycyrrhizate Improves Intestinal Mucosal Healing by Modulating Extracellular Matrix Remodeling Genes and Restoring Epithelial Barrier Functions.

Gut mucosal healing (MH) is considered a key therapeutic target and prognostic parameter in the management of inflammatory bowel disease (IBD). The dipotassium glycyrrhizate (DPG), a salt of the glycoconjugated triterpene glycyrrhizin, has been shown to inhibit the High Mobility Group Box 1 (HMGB1) protein, an allarmin strongly implicated in the pathogenesis of most inflammatory and auto-immune disorders. Here we discuss new insights on how DPG acts on MH comparing the acute phase and the recovery phase from experimental colitis in mice.

Transcription Factor ZNF281: A Novel Player in Intestinal Inflammation and Fibrosis.

Recent evidences reveal the occurrence of a close relationship among epithelial to mesenchymal transition (EMT), chronic inflammation and fibrosis. ZNF281 is an EMT-inducing transcription factor (EMT-TF) involved in the regulation of pluripotency, stemness, and cancer. The aim of this study was to investigate , and a possible role of ZNF281 in the onset and progression of intestinal inflammation.

Faecal high mobility group box 1 in children with celiac disease: A pilot study.

Background: Celiac disease (CD) is a gluten-related immunological disorder resulting in inflammatory enteropathy.

Aims: We assessed a stool marker of intestinal inflammation, the HMGB1 protein, in children with CD on a gluten free diet (GFD) at baseline and at follow up (FU).

Methods: Thirty-nine children were investigated at diagnosis and at FU.

Quantitative Assessment of Shotgun Metagenomics and 16S rDNA Amplicon Sequencing in the Study of Human Gut Microbiome.

The analysis of microbiota composition in humans, animals, and built environments is important because of emerging roles and applications in a broad range of disease and ecological phenotypes. Next Generation Sequencing is the current method of choice to characterize microbial community composition. The taxonomic profile of a microbial community can be obtained either by shotgun analysis of random DNA fragments or through 16S ribosomal RNA gene (rDNA) amplicon sequencing.

Krill oil, vitamin D and Lactobacillus reuteri cooperate to reduce gut inflammation.

Current research into original therapies to treat intestinal inflammation is focusing on no-drug therapies. KLD is a mixture of krill oil (KO), probiotic Lactobacillus reuteri (LR), and vitamin D (VitD3). The aim of this study was to assess in vitro and in vivo the potential cooperative effects of KLD in reducing gut inflammation.

RIP3 AND pMLKL promote necroptosis-induced inflammation and alter membrane permeability in intestinal epithelial cells.

Background: Necroptosis is an inflammatory form of programmed cell death requiring receptor-interacting protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL).

Aims: The aim of this study is to examine in depth in vitro and ex vivo the contribution of necroptosis to intestinal inflammation.

Methods: In vitro: we used an intestinal cell line, HCT116RIP3, produced in our laboratory and overexpressing RIP3.

Fecal HMGB1 Reveals Microscopic Inflammation in Adult and Pediatric Patients with Inflammatory Bowel Disease in Clinical and Endoscopic Remission.

Background: Fecal high mobility group box 1 (HMGB1) has been suggested to be a novel noninvasive biomarker of gut inflammation. We aimed to assess the reliability of fecal HMGB1, compared with fecal calprotectin (FC), in detecting intestinal inflammation in pediatric and adult patients with inflammatory bowel disease (IBD) and to evaluate the accuracy of HMGB1 in identifying patients with IBD in clinical and endoscopic remission who still have histologic features of inflammation.

Methods: Stool samples from 85 children with IBD (49 Crohn's disease [CD] and 36 ulcerative colitis [UC] and 119 adults [57 Crohn's disease and 62 ulcerative colitis]) were analyzed for the study.

NOD2 induces autophagy to control AIEC bacteria infectiveness in intestinal epithelial cells.

Objective: The importance of autophagy in mechanisms underlying inflammation has been highlighted. Downstream effects of the bacterial sensor NOD2 include autophagy induction. Recently, a relationship between defects in autophagy and adherent/invasive Escherichia coli (AIEC) persistence has emerged.

Krill oil reduces intestinal inflammation by improving epithelial integrity and impairing adherent-invasive Escherichia coli pathogenicity.

Background: Krill oil is a marine derived oil rich in phospholipids, astaxanthin and omega-3 fatty acids. Several studies have found benefits of krill oil against oxidative and inflammatory damage.

Aims: We aimed at assessing the ability of krill oil to reduce intestinal inflammation by improving epithelial barrier integrity, increasing cell survival and reducing pathogenicity of adherent-invasive Escherichia coli.

Dipotassium glycyrrhizate via HMGB1 or AMPK signaling suppresses oxidative stress during intestinal inflammation.

Aims: Oxidative stress and inflammation are always associated. Appropriate management of oxidative mediators may represent a therapeutic strategy to reduce inflammation, and use of antioxidant can be protective against inflammatory diseases. Glycyrrhizin (GL) plays an anti-inflammatory and antioxidant effect by inhibiting high mobility group box 1 (HMGB1) or 11-β-hydroxysteroid dehydrogenase type II (11βHSD2) enzyme.

Role of HMGB1 as a suitable biomarker of subclinical intestinal inflammation and mucosal healing in patients with inflammatory bowel disease.

Background: Noninvasive biomarkers of high- and low-grade intestinal inflammation and of mucosal healing (MH) in patients with inflammatory bowel disease are currently lacking. We have recently shown that fecal high mobility group box 1 (HMGB1) protein is a novel biomarker of gut inflammation. We aimed at investigating in a mouse model if HMGB1 was able to foresee both a clinically evident and a subclinical gut inflammation and if its normalization indicated MH.