scholarly journals Exosomes as a new pain biomarker opportunity

2020 ◽  
Vol 16 ◽  
pp. 174480692095780
Author(s):  
Simona D’Agnelli ◽  
Maria C Gerra ◽  
Elena Bignami ◽  
Lars Arendt-Nielsen
Keyword(s):  
Biological Fluids ◽  
Pain Syndrome ◽  
Cellular Origin ◽  
Non Invasive ◽  
Distant Target ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Therapeutic Tools ◽  
Molecular Patterns ◽  
Potential Use

Exosomes are extracellular microvesicles implicated in intercellular communication with ability to transfer cargo molecules, including protein, lipids, and nucleic acids, at both close and distant target sites. It has been shown that exosomes are implicated in physiological and pathological processes. In recent years, the interest on exosomes’ role in many pain states has increased. Their involvements in pain processes have been demonstrated by studies on different chronic pain diseases, both inflammatory and neuropathic, such as osteoarthritis, rheumatoid arthritis, inflammatory bowel diseases, neurodegenerative pathologies, complex regional pain syndrome, and peripheral nerve injury. Animal and clinical studies investigated exosomes-based treatments, showing their ability to improve painful symptoms with fewer side effects, with potential immunoprotective and anti-inflammatory effect. Specific molecular patterns characterize exosomes’ cargo according to the cellular origin, epigenetic modifications, environmental state, and stressor factors. Therefore, the identification of specific cargo’s profile associated to pain states may lead to recognize specific pathological states and to consider the use of exosomes as biomarkers of diseases. Furthermore, exosomes’ ability to transfer information and their presence in many accessible biological fluids suggest a potential use as novel non-invasive therapeutic tools in pain field.

scholarly journals Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Luca Pastorelli ◽  
Elena Dozio ◽  
Laura Francesca Pisani ◽  
Massimo Boscolo-Anzoletti ◽  
Elena Vianello ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Intestinal Barrier Function ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Molecular Patterns ◽  
D Dimer

Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragmentF1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer andF1+2measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.

scholarly journals Review Article. Absent in melanoma 2 (AIM2) in the intestine: diverging actions with converging consequences

Inflammasome ◽  
2017 ◽  
Vol 3 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Wiebe Vanhove ◽  
Paul M. Peeters ◽  
Isabelle Cleynen ◽  
Gert Van Assche ◽  
Marc Ferrante ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Epithelial ◽  
Intestinal Immunity ◽  
Intestinal Homeostasis ◽  
Caspase 1 ◽  
Essential Components ◽  
Food Antigens ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Molecular Patterns

AbstractThe intestinal mucosa is a difficult environment to maintain homeostasis as it is constantly challenged by microbial and food antigens. Maintaining an intact epithelial barrier, a continuous turnover of intestinal epithelial cells and normobiosis of the gut microbiota are essential components to prevent intestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Inflammasomes are critical immune regulators that are involved in all of these processes. They are multiprotein complexes able to assemble upon interaction with a noxious stimulus that will subsequently lead to caspase-1 activation. Activated caspase-1 will orchestrate the maturation and release of proinflammatory cytokines IL-1β and IL-18, and induce pyroptosis, an inflammatory form of cell death. Both cytokine release and pyroptosis are initiated after detection of molecular patterns by a distinct inflammasome sensor protein. Absent in melanoma 2 (AIM2) is such an inflammasome sensor that specifically responds to the presence of double stranded DNA (dsDNA) in the cytoplasm, leading to the recruitment and activation of caspase-1. Recent studies revealed additional roles of AIM2 in controlling epithelial cell proliferation, tight junction expression and the microbiome. Therefore, AIM2 plays a significant role in maintaining intestinal homeostasis. This review focuses on the multifunctional role of AIM2 in intestinal homeostasis by regulating intestinal immunity and preventing colorectal cancer development.

scholarly journals P211 Pseudopolyps are associated with increased fecal calprotectin levels in patients with Inflammatory Bowel Disease in clinical and endoscopic remission

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S270-S271
Author(s):  
I Spigarelli De Rábago ◽  
C Suárez Ferrer ◽  
J Poza Cordón ◽  
E Martín Arranz ◽  
M Sánchez Azofra ◽  
...  
Keyword(s):  
Fecal Calprotectin ◽  
Clinical Settings ◽  
Optimal Cutoff ◽  
Non Invasive ◽  
Endoscopic Remission ◽  
Active Colitis ◽  
Bowel Diseases ◽  
Endoscopic Score ◽  
Inflammatory Bowel ◽  
Histological Activity

Abstract Background Fecal calprotectin (FC) has become a fundamental tool in the non-invasive monitorization of activity in patients with inflammatory bowel diseases (IBD). However, there is still debate over the choice of the optimal cut-off point for the different clinical settings. The aim of this study is to analyze whether the presence of pseudopolyps and their characteristics have an impact on the value of FC and should therefore be taken into account when deciding the optimal cutoff values. Methods A single-centered, retrospective analysis including data from patients with colonic Crohn′s disease or Ulcerative colitis who underwent colonoscopy for dysplasia screening at our center between 2018 and 2019. Patients that did not have a FC registered within 8 months from to the colonoscopy, or that did not maintain clinical remission between the colonoscopy and the measurement of the FC, were excluded. Patients that had activity in the colonoscopy (Mayo endoscopic score >0, SESCD >0) were also excluded. Results 73 patients were included. 26 (35.6%) of them had pseudopolyps in the colonoscopy. The median value of the FC was significantly different in patients with pseudopolyps (110.1 µg/g, CI 95% [48.6–171.5]) compared to those without them (52.5 µg/g, CI 95% [29.9–75.1]). In 11 (42.3%) of the patients with pseudopolyps, biopsies were taken, observing histological activity in 3 of them (27.3%) and no inflammatory activity in the other 8 (72.7%). We found that FC was higher in patients with inflammatory polyps (119.0 µg/g) in comparison to those without histological activity in their pseudopolyps (96.9 µg/g); however, these results were not statistically significant. The location of the pseudopolyps had no influence over the FC in our study. In addition, no correlation was found between the presence of polyps or diverticula and FC. Conclusion In our study, the presence of pseudopolyps is associated with significantly higher levels of FC. Moreover, our results suggest a tendency towards higher FC in patients who had active colitis in the histological samples of their pseudopolyps.

scholarly journals New Metabolic and Genetic Biomarkers for Diagnosis of Ulcerative Colitis

2021 ◽  
Author(s):  
Elena Emilia Tudoroniu ◽  
Mihaela Andreea Costache ◽  
Maria-Andreea Stancu ◽  
Anca Lucia Pop
Keyword(s):  
Ulcerative Colitis ◽  
Case Series ◽  
Diagnostic Value ◽  
Eligibility Criteria ◽  
Non Invasive ◽  
Randomized Controlled ◽  
Genetic Biomarkers ◽  
Bowel Diseases ◽  
Invasive Method ◽  
Inflammatory Bowel

Ulcerative colitis (UC) is one of the two disorders known as inflammatory bowel diseases (IBD) along with Crohn’s disease (CD), with complex pathogenesis, requiring costly invasive investigations. Objective: to examine the most recent biomarkers proposed for UC diagnosis; to establish the strategy used to make the differential diagnosis between UC and CD relying on these biomarkers, also adding the benefit of finding new non-invasive tools in managing this condition. The search was performed in a single database (Web of Science) using the specific keywords „ulcerative colitis”, „biomarkers” and „diagnosis” for the last five years. Study eligibility criteria: clinical trials on adults and pediatric patients with ulcerative colitis compared with Crohn’s disease. Results: We selected 57 studies, randomized controlled trials (RCTs) and clinical case series (CCS), summarizing the latest most specific biomarkers in diagnosis of UC. Limitations: we considered RCTs and CCS from one database, limited to the search topics. Our findings indicate a important number of potential biomarkers with diagnostic value, which bring the advantage of a non-invasive method to approach this challenging disorder.

scholarly journals Dynamic, Transient, and Robust Increase in the Innervation of the Inflamed Mucosa in Inflammatory Bowel Diseases

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2253
Author(s):  
Miguel Gonzalez Acera ◽  
Marvin Bubeck ◽  
Fabrizio Mascia ◽  
Leonard Diemand ◽  
Gregor Sturm ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Inflammatory Bowel Diseases ◽  
Cell Activation ◽  
Immune Cell ◽  
Bowel Diseases ◽  
Treatment Naïve ◽  
Inflammatory Bowel ◽  
Molecular Patterns ◽  
The Impact

Inflammatory bowel diseases (IBD) are characterized by chronic dysregulation of immune homeostasis, epithelial demise, immune cell activation, and microbial translocation. Each of these processes leads to proinflammatory changes via the release of cytokines, damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs), respectively. The impact of these noxious agents on the survival and function of the enteric nervous system (ENS) is poorly understood. Here, we show that in contrast to an expected decrease, experimental as well as clinical colitis causes an increase in the transcript levels of enteric neuronal and glial genes. Immunostaining revealed an elevated neuronal innervation of the inflamed regions of the gut mucosa. The increase was seen in models with overt damage to epithelial cells and models of T cell-induced colitis. Transcriptomic data from treatment naïve pediatric IBD patients also confirmed the increase in the neuroglial genes and were replicated on an independent adult IBD dataset. This induction in the neuroglial genes was transient as levels returned to normal upon the induction of remission in both mouse models as well as colitis patients. Our data highlight the dynamic and robust nature of the enteric nervous system in colitis and open novel questions on its regulation.

P162 RAID-Monitor: a new non-invasive method to determine endoscopic activity in inflammatory bowel diseases

2019 ◽  
Vol 13 (Supplement_1) ◽  
pp. S169-S170
Author(s):  
J Amoedo ◽  
S Ramió-Pujol ◽  
A Bahí ◽  
C Puig-Amiel ◽  
L Oliver ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Non Invasive ◽  
Bowel Diseases ◽  
Invasive Method ◽  
Inflammatory Bowel

Particularities of IBD Trials in Children

2019 ◽  
Vol 25 (1) ◽  
pp. 69-72 ◽  
Author(s):  
Dan Turner
Keyword(s):  
Recent Trend ◽  
Safety Data ◽  
New Drugs ◽  
Phase 3 ◽  
Non Invasive ◽  
Randomized Controlled ◽  
Adult Phase ◽  
Bowel Diseases ◽  
Pediatric Trial ◽  
Inflammatory Bowel

Pediatric inflammatory bowel diseases (IBD) are similar to the adult-onset type in many aspects, including the necessity of high-quality randomized controlled trials. However, recruiting children into clinical trials is conceptually more challenging than in adults. Furthermore, the long delay between adult and pediatric approval of new drugs leads not only to the unbearable extensive use of these drugs as off-label without appropriate dosing and safety data but also to more challenges when eventually the pediatric trial is performed. This review offers possible solutions to age-specific pitfalls in performing trials in pediatric IBD. Many of the challenges could be adequately addressed by accepting full extrapolation of efficacy from adult trials. This is advisable if small pharmacokinetics/ pharmacodynamics (PK/PD) studies show similarity to adult data. Then, pediatric trials can focus on dosing and safety while avoiding the controversial use of placebo. Judicious use of non-invasive activity scores and biomarkers, providing immediate and effective treatment in active disease and ensuring equipoise of treatments both within and outside the trial are the mainstay of a feasible trial in children. The recent trend of including adolescents in adult phase-3 trials addresses some obstacles but introduces others. Acknowledging and addressing these age-specific challenges would facilitate pediatric drug development in IBD.

scholarly journals Emerging Role of Exosomes in Diagnosis and Treatment of Infectious and Inflammatory Bowel Diseases

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1111 ◽  
Author(s):  
Anaïs Larabi ◽  
Nicolas Barnich ◽  
Hang Thi Thu Nguyen
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Intestinal Inflammation ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Bowel Diseases ◽  
Therapeutic Molecules ◽  
Inflammatory Bowel

To communicate with each other, cells release exosomes that transfer their composition, including lipids, proteins and nucleic acids, to neighboring cells, thus playing a role in various pathophysiological processes. During an infection with pathogenic bacteria, such as adherent-invasive E. coli (AIEC) associated with Crohn disease, exosomes secreted by infected cells can have an impact on the innate immune responses of surrounding cells to infection. Furthermore, inflammation can be amplified via the exosomal shuttle during infection with pathogenic bacteria, which could contribute to the development of the associated disease. Since these vesicles can be released in various biological fluids, changes in exosomal content may provide a means for the identification of non-invasive biomarkers for infectious and inflammatory bowel diseases. Moreover, evidence suggests that exosomes could be used as vaccines to prime the immune system to recognize and kill invading pathogens, and as therapeutic components relieving intestinal inflammation. Here, we summarize the current knowledge on the role of exosomes in bacterial infections and highlight their potential use as biomarkers, vaccines and conveyers of therapeutic molecules in inflammatory bowel diseases.

scholarly journals Capturing the Biologic Onset of Inflammatory Bowel Diseases: Impact on Translational and Clinical Science

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 548 ◽  
Author(s):  
Dario Sorrentino ◽  
Vu Q. Nguyen ◽  
Maithili V. Chitnavis
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Clinical Stage ◽  
Major Drawback ◽  
Disease Etiology ◽  
Non Invasive ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Potential Impact ◽  
Made In

While much progress has been made in the last two decades in the treatment and the management of inflammatory bowel diseases (IBD)—both ulcerative colitis (UC) and Crohn’s Disease (CD)—as of today these conditions are still diagnosed only after they have become symptomatic. This is a major drawback since by then the inflammatory process has often already caused considerable damage and the disease might have become partially or totally unresponsive to medical therapy. Late diagnosis in IBD is due to the lack of accurate, non-invasive indicators that would allow disease identification during the pre-clinical stage—as it is often done in many other medical conditions. Here, we will discuss what is known about the biologic onset and pre-clinical CD with an emphasis on studies conducted in patients’ first degree relatives. We will then review the possible strategies to diagnose IBD very early in time including screening, available disease markers and imaging, and the possible clinical implications of treating these conditions at or close to their biologic onset. Later, we will review the potential impact of conducting translational research in IBD during the pre-clinical stage, especially focusing on the role of the microbiome in disease etiology and pathogenesis. Finally, we will highlight possible future developments in the field and how they can impact IBD management and our scientific knowledge of these conditions.

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