scholarly journals Proteolytic Cleavage of Bioactive Peptides and Protease-Activated Receptors in Acute and Post-Colitis

2021 ◽  
Vol 22 (19) ◽  
pp. 10711
Author(s):  
Michelle De De bruyn ◽  
Hannah Ceuleers ◽  
Nikita Hanning ◽  
Maya Berg ◽  
Joris G. De De Man ◽  
...  
Keyword(s):  
Bioactive Peptides ◽  
Colonic Tissue ◽  
Trinitrobenzenesulfonic Acid ◽  
Acute Colitis ◽  
Protease Activated Receptors ◽  
Inflammatory Phase ◽  
Tethered Ligand ◽  
Inflammatory Bowel ◽  
Irritable Bowel ◽  
The One

The protease activity in inflammatory bowel disease (IBD) and irritable bowel syndrome has been studied extensively using synthetic fluorogenic substrates targeting specific sets of proteases. We explored activities in colonic tissue from a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model by investigating the cleavage of bioactive peptides. Pure trypsin- and elastase-like proteases on the one hand and colonic tissue from rats with TNBS-induced colitis in the acute or post-inflammatory phase on the other, were incubated with relevant peptides to identify their cleavage pattern by mass spectrometry. An increased cleavage of several peptides was observed in the colon from acute colitis rats. The tethered ligand (TL) sequences of peptides mimicking the N-terminus of protease-activated receptors (PAR) 1 and 4 were significantly unmasked by acute colitis samples and these cleavages were positively correlated with thrombin activity. Increased cleavage of β-endorphin and disarming of the TL-sequence of the PAR3-based peptide were observed in acute colitis and linked to chymotrypsin-like activity. Increased processing of the enkephalins points to the involvement of proteases with specificities different from trypsin- or chymotrypsin-like enzymes. In conclusion, our results suggest thrombin, chymotrypsin-like proteases and a set of proteases with different specificities as potential therapeutic targets in IBD.

scholarly journals Engineering of an Anti-Inflammatory Peptide Based on the Disulfide-Rich Linaclotide Scaffold

Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 97
Author(s):  
Claudia Cobos ◽  
Paramjit Bansal ◽  
Linda Jones ◽  
Phurpa Wangchuk ◽  
David Wilson ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Acute Colitis ◽  
Agonist Peptide ◽  
Amino Acid Peptide ◽  
Guanylate Cyclase C ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Irritable Bowel ◽  
Drug Leads

Inflammatory bowel diseases are a set of complex and debilitating diseases, for which there is no satisfactory treatment. Peptides as small as three amino acids have been shown to have anti-inflammatory activity in mouse models of colitis, but they are likely to be unstable, limiting their development as drug leads. Here, we have grafted a tripeptide from the annexin A1 protein into linaclotide, a 14-amino-acid peptide with three disulfide bonds, which is currently in clinical use for patients with chronic constipation or irritable bowel syndrome. This engineered disulfide-rich peptide maintained the overall fold of the original synthetic guanylate cyclase C agonist peptide, and reduced inflammation in a mouse model of acute colitis. This is the first study to show that this disulfide-rich peptide can be used as a scaffold to confer a new bioactivity.

scholarly journals Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives

2020 ◽  
Vol 9 (11) ◽  
pp. 3535
Author(s):  
Marcantonio Gesualdo ◽  
Felice Rizzi ◽  
Silvia Bonetto ◽  
Stefano Rizza ◽  
Federico Cravero ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Current Knowledge ◽  
Research Area ◽  
Fecal Microbiota ◽  
Pancreatic Diseases ◽  
Rheumatologic Diseases ◽  
Inflammatory Bowel ◽  
Irritable Bowel ◽  
The One

Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.

Are Viruses and Parasites Linked to Celiac Disease? A Question that Still has no Definite Answer

2019 ◽  
Vol 20 (14) ◽  
pp. 1181-1193 ◽  
Author(s):  
Aref Shariati ◽  
Hamid R. Aslani ◽  
Mohammad R.H. Shayesteh ◽  
Ali Taghipour ◽  
Ahmad Nasser ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Multiple Roles ◽  
Barr Virus ◽  
The People ◽  
Intestinal Infections ◽  
Inflammatory Bowel ◽  
Epstein Barr ◽  
Irritable Bowel ◽  
Related Proteins

Celiac Disease (CD) is a complex autoimmune enteropathy of the small intestine that commonly occurs in genetically predisposed individuals due to intake of gluten and related proteins. Gluten consumption, duration of breast-feeding, various infections, especially frequent intestinal infections, vaccinations and use of antibiotics can be linked to CD. It is predicted that it affects 1% of the global population and its incidence rate is increasing. Most of the people with the HLA-DQ2 or HLADQ8 are at a higher risk of developing this disease. The link between infections and autoimmune diseases has been very much considered in recent years. In several studies, we explained that pathogenic and non-pathogenic microorganisms might have multiple roles in initiation, exacerbation, and development of Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). In various studies, the relationship between infections caused by viruses, such as Epstein-Barr Virus (EBV), Rotavirus, Hepatitis C (HCV), Hepatitis B virus (HBV), Cytomegalovirus (CMV), and Influenza virus, and parasites including Giardia spp. and Toxoplasma gondii with CD has been raised. However, increasing evidence proposes that some of these microorganisms, especially helminths, can also have protective and even therapeutic roles in the CD process. Therefore, in order to determine the role of microorganisms in the process of this disease, we attempted to summarize the evidence suggesting the role of viral and parasitic agents in pathogenesis of CD.

scholarly journals BIOSIMILARS IN INFLAMMATORY BOWEL DISEASES: an important moment for Brazilian gastroenterologists

2015 ◽  
Vol 52 (1) ◽  
pp. 76-80 ◽  
Author(s):  
Fábio Vieira TEIXEIRA ◽  
Paulo Gustavo KOTZE ◽  
Aderson Omar Mourão Cintra DAMIÃO ◽  
Sender Jankiel MISZPUTEN
Keyword(s):  
Small Molecules ◽  
Inflammatory Bowel Diseases ◽  
Generic Drugs ◽  
Specific Data ◽  
Chemical Structures ◽  
Bowel Diseases ◽  
Original Product ◽  
Inflammatory Bowel ◽  
The One ◽  
Extrapolation Of Indications

ABSTRACT Biosimilars are not generic drugs. These are more complex medications than small molecules, with identical chemical structures of monoclonal antibodies that lost their patency over time. Besides identical to the original product at the end, the process of achieving its final forms differs from the one used in the reference products. These differences in the formulation process can alter final outcomes such as safety and efficacy of the drugs. Recently, a biosimilar of Infliximab was approved in some countries, even to the management of inflammatory bowel diseases. However, this decision was based on studies performed in rheumatologic conditions such as rheumatoid arthritis and ankylosing spondylitis. Extrapolation of the indications from rheumatologic conditions was done for Crohn’s disease and ulcerative colitis based on these studies. In this article, the authors explain possible different mechanisms in the pathogenesis between rheumatologic conditions and inflammatory bowel diseases, that can lead to different actions of the medications in different diseases. The authors also alert the gastroenterological community for the problem of extrapolation of indications, and explain in full details the reasons for being care with the use of biosimilars in inflammatory bowel diseases without specific data from trials performed in this scenario.

Impact of titanium dioxide nanoparticles on intestinal community in the 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced acute colitis mice and the intervention effect of vitamin E

Nanoscale ◽  
2020 ◽  
Author(s):  
Yanjun Gao ◽  
Tingyu Li ◽  
Shuming Duan ◽  
Lizhi Lv ◽  
Yuan Li ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Titanium Dioxide ◽  
Vitamin E ◽  
Titanium Dioxide Nanoparticles ◽  
Trinitrobenzenesulfonic Acid ◽  
Acute Colitis ◽  
Intervention Effect ◽  
Tio2 Nps

Titanium dioxide nanoparticles (TiO2-NPs) is widely applicated as additives in foods for its excellent whitening and brightening capability. Although the toxicity and antibacterial activity of TiO2-NPs has been extensively studied,...

scholarly journals The Colonic Tissue Levels of TLR2, TLR4 and Nitric Oxide in Patients with Irritable Bowel Syndrome

2016 ◽  
Vol 55 (9) ◽  
pp. 1043-1048 ◽  
Author(s):  
Erdem Koçak ◽  
Erdem Akbal ◽  
Seyfettin Köklü ◽  
Bilal Ergül ◽  
Murat Can
Keyword(s):  
Nitric Oxide ◽  
Irritable Bowel Syndrome ◽  
Colonic Tissue ◽  
Tissue Levels ◽  
Irritable Bowel
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