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Digestive Inflammation and New Therapeutical Targets

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 12625

Special Issue Editors


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Guest Editor
UMR 1149 Inserm, Centre de Recherche sur l’Inflammation (CRI), Université de Paris, 75018 Paris, France
Interests: GPCR; signaling pathways; gastroenterology; epithelial cells; chronic inflammation; digestive cancers; apoptosis; neuropeptides; pharmacology; structure function

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Guest Editor
INSERM UMR1149, ERL CNRS 8252, Université Paris Diderot, F-75018 Paris, France
Interests: pancreas; transcription factor; development; pancreatitis; pancreatic cancer; epigenetics

Special Issue Information

Dear Colleagues,

Chronic inflammatory gastrointestinal diseases (CIGDs) are one of the most common forms of inflammatory disease in humans. Even though CIGDs can affect any part of the gastrointestinal tract, they mainly affect the liver, the pancreas, the bile duct, the intestine/colon, as well as the stomach and esophagus. The main diseases associated with CIGDs are hepatitis, pancreatitis, cholangitis, intestinal bowel diseases (IBD), gastritis, and esophagitis. Depending on the organ involved, CIGDs have different etiologies, mechanisms, and symptoms. CIGDs have several common characteristics, including dysregulation of the immune system, imbalance of pro- and anti-inflammatory processes, disruption of the epithelium barrier function, and the involvement of microbiota or viruses. Moreover, it is now widely recognized that CIGDs represent an important risk factor in the development of cancers. Relationships between malignancies and chronic inflammation were observed for various digestive cancers, including esophagus, stomach, liver, bile duct, pancreas and colorectal cancers. Although the therapeutic arsenal for the treatment of CIGDs has developed considerably over the last decade, much remains to be done in this field.

For this Special Issue, which will be published in the International Journal of Molecular Science (IJMS), authors are welcome to submit original research articles, reviews, or shorter perspective articles dedicated to the identification of new molecular mechanisms and putative therapeutical targets in the context of CIGDs and/or the sequence CIGD cancer.

We look forward to your contributions to this Special Issue.

Dr. Alain Couvineau
Dr. Cécile Haumaitre
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • digestive chronic inflammation
  • epithelium barrier
  • microbiota
  • precancerous lesions
  • cancer

Published Papers (7 papers)

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Editorial

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4 pages, 191 KiB  
Editorial
Special Issue: “Digestive Inflammation and New Therapeutical Targets”
by Alain Couvineau and Cécile Haumaitre
Int. J. Mol. Sci. 2024, 25(8), 4361; https://doi.org/10.3390/ijms25084361 - 15 Apr 2024
Viewed by 273
Abstract
Inflammatory diseases commonly associated with humans are chronic inflammatory gastrointestinal diseases (CIGDs) [...] Full article
(This article belongs to the Special Issue Digestive Inflammation and New Therapeutical Targets)

Research

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15 pages, 2010 KiB  
Article
The Effect of Sex-Specific Differences on IL-10−/− Mouse Colitis Phenotype and Microbiota
by Maite Casado-Bedmar, Maryline Roy and Emilie Viennois
Int. J. Mol. Sci. 2023, 24(12), 10364; https://doi.org/10.3390/ijms241210364 - 20 Jun 2023
Cited by 2 | Viewed by 1680
Abstract
Sexual dimorphism is an important factor in understanding various diseases, including inflammatory bowel disease (IBD). While females typically exhibit stronger immune responses, the role of sex in IBD remains unclear. This study aimed to explore the sex-dependent differences and inflammatory susceptibility in the [...] Read more.
Sexual dimorphism is an important factor in understanding various diseases, including inflammatory bowel disease (IBD). While females typically exhibit stronger immune responses, the role of sex in IBD remains unclear. This study aimed to explore the sex-dependent differences and inflammatory susceptibility in the most extensively used IBD mouse model as they developed colitis. We monitored IL10-deficient mice (IL-10−/−) up to 17 weeks of age and characterized their colonic and fecal inflammatory phenotype, as well as their microbiota changes. Here, we originally identified IL-10−/− female mice as more prone to developing intestinal inflammation, with an increase in fecal miR-21, and dysbiosis with more detrimental characteristics compared to males. Our findings provide valuable insights into the sex-based differences in the pathophysiology of colitis and emphasize the importance of considering sex in experimental designs. Moreover, this study paves the way for future investigations aiming at addressing sex-related differences for the development of adequate disease models and therapeutic strategies, ideally enabling personalized medicine. Full article
(This article belongs to the Special Issue Digestive Inflammation and New Therapeutical Targets)
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13 pages, 1828 KiB  
Article
Efficiency of Orexin-A for Inflammatory Flare and Mucosal Healing in Experimental Colitis: Comparison with the Anti-TNF Alpha Infliximab
by Anne Blais, Annaïg Lan, François Blachier, Robert Benamouzig, Pauline Jouet and Alain Couvineau
Int. J. Mol. Sci. 2023, 24(11), 9554; https://doi.org/10.3390/ijms24119554 - 31 May 2023
Viewed by 1343
Abstract
Inflammatory bowel diseases are chronic inflammation of the intestinal mucosa characterized by relapsing–remitting cycle periods of variable duration. Infliximab (IFX) was the first monoclonal antibody used for the treatment of Crohn’s disease and ulcerative colitis (UC). High variability between treated patients and loss [...] Read more.
Inflammatory bowel diseases are chronic inflammation of the intestinal mucosa characterized by relapsing–remitting cycle periods of variable duration. Infliximab (IFX) was the first monoclonal antibody used for the treatment of Crohn’s disease and ulcerative colitis (UC). High variability between treated patients and loss of IFX efficiency over time support the further development of drug therapy. An innovative approach has been suggested based on the presence of orexin receptor (OX1R) in the inflamed human epithelium of UC patients. In that context, the aim of this study was to compare, in a mouse model of chemically induced colitis, the efficacy of IFX compared to the hypothalamic peptide orexin-A (OxA). C57BL/6 mice received 3.5% dextran sodium sulfate (DSS) in drinking water for 5 days. Since the inflammatory flare was maximal at day 7, IFX or OxA was administered based on a curative perspective at that time for 4 days using intraperitoneal injection. Treatment with OxA promoted mucosal healing and decreased colonic myeloperoxidase activity, circulating concentrations of lipopolysaccharide-binding protein, IL-6 and tumor necrosis factor alpha (TNFα) and decreased expression of genes encoding cytokines in colonic tissues with better efficacy than IFX allowing for more rapid re-epithelization. This study demonstrates the comparable anti-inflammatory properties of OxA and IFX and shows that OxA is efficient in promoting mucosal healing, suggesting that OxA treatment is a promising new biotherapy. Full article
(This article belongs to the Special Issue Digestive Inflammation and New Therapeutical Targets)
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17 pages, 5193 KiB  
Article
PPAR-Gamma Orchestrates EMT, AGE, and Cellular Senescence Pathways in Colonic Epithelium and Restrains the Progression of IBDs
by Simona Pompili, Antonella Vetuschi, Giovanni Latella, Amarildo Smakaj, Roberta Sferra and Alfredo Cappariello
Int. J. Mol. Sci. 2023, 24(10), 8952; https://doi.org/10.3390/ijms24108952 - 18 May 2023
Cited by 6 | Viewed by 1596
Abstract
Intestinal fibrosis, the most common complication of inflammatory bowel disease (IBD), is characterized by an uncontrolled deposition of extracellular matrix proteins leading to complications resolvable only with surgery. Transforming growth factor is the key player in the epithelial-mesenchymal transition (EMT) and fibrogenesis process, [...] Read more.
Intestinal fibrosis, the most common complication of inflammatory bowel disease (IBD), is characterized by an uncontrolled deposition of extracellular matrix proteins leading to complications resolvable only with surgery. Transforming growth factor is the key player in the epithelial-mesenchymal transition (EMT) and fibrogenesis process, and some molecules modulating its activity, including peroxisome proliferator-activated receptor (PPAR)-γ and its agonists, exert a promising antifibrotic action. The purpose of this study is to evaluate the contribution of signaling other than EMT, such as the AGE/RAGE (advanced glycation end products/receptor of AGEs) and the senescence pathways, in the etiopathogenesis of IBD. We used human biopsies from control and IBD patients, and we used a mouse model of colitis induced by dextran-sodium-sulfate (DSS), without/with treatments with GED (PPAR-gamma-agonist), or 5-aminosalicylic acid (5-ASA), a reference drug for IBD treatment. In patients, we found an increase in EMT markers, AGE/RAGE, and senescence signaling activation compared to controls. Consistently, we found the overexpression of the same pathways in DSS-treated mice. Surprisingly, the GED reduced all the pro-fibrotic pathways, in some circumstances more efficiently than 5-ASA. Results suggest that IBD patients could benefit from a combined pharmacological treatment targeting simultaneously different pathways involved in pro-fibrotic signals. In this scenario, PPAR-gamma activation could be a suitable strategy to alleviate the signs and symptoms of IBD and also its progression. Full article
(This article belongs to the Special Issue Digestive Inflammation and New Therapeutical Targets)
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Review

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44 pages, 2411 KiB  
Review
Long Non-Coding RNAs and Their “Discrete” Contribution to IBD and Johne’s Disease—What Stands out in the Current Picture? A Comprehensive Review
by Kostas A. Triantaphyllopoulos
Int. J. Mol. Sci. 2023, 24(17), 13566; https://doi.org/10.3390/ijms241713566 - 01 Sep 2023
Cited by 5 | Viewed by 1473
Abstract
Non-coding RNAs (ncRNA) have paved the way to new perspectives on the regulation of gene expression, not only in biology and medicine, but also in associated fields and technologies, ensuring advances in diagnostic means and therapeutic modalities. Critical in this multistep approach are [...] Read more.
Non-coding RNAs (ncRNA) have paved the way to new perspectives on the regulation of gene expression, not only in biology and medicine, but also in associated fields and technologies, ensuring advances in diagnostic means and therapeutic modalities. Critical in this multistep approach are the associations of long non-coding RNA (lncRNA) with diseases and their causal genes in their networks of interactions, gene enrichment and expression analysis, associated pathways, the monitoring of the involved genes and their functional roles during disease progression from one stage to another. Studies have shown that Johne’s Disease (JD), caused by Mycobacterium avium subspecies partuberculosis (MAP), shares common lncRNAs, clinical findings, and other molecular entities with Crohn’s Disease (CD). This has been a subject of vigorous investigation owing to the zoonotic nature of this condition, although results are still inconclusive. In this review, on one hand, the current knowledge of lncRNAs in cells is presented, focusing on the pathogenesis of gastrointestinal-related pathologies and MAP-related infections and, on the other hand, we attempt to dissect the associated genes and pathways involved. Furthermore, the recently characterized and novel lncRNAs share common pathologies with IBD and JD, including the expression, molecular networks, and dataset analysis results. These are also presented in an attempt to identify potential biomarkers pertinent to cattle and human disease phenotypes. Full article
(This article belongs to the Special Issue Digestive Inflammation and New Therapeutical Targets)
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21 pages, 1520 KiB  
Review
Acinar-to-Ductal Metaplasia (ADM): On the Road to Pancreatic Intraepithelial Neoplasia (PanIN) and Pancreatic Cancer
by Louis Marstrand-Daucé, Diane Lorenzo, Anaïs Chassac, Pascal Nicole, Anne Couvelard and Cécile Haumaitre
Int. J. Mol. Sci. 2023, 24(12), 9946; https://doi.org/10.3390/ijms24129946 - 09 Jun 2023
Cited by 3 | Viewed by 4196
Abstract
Adult pancreatic acinar cells show high plasticity allowing them to change in their differentiation commitment. Pancreatic acinar-to-ductal metaplasia (ADM) is a cellular process in which the differentiated pancreatic acinar cells transform into duct-like cells. This process can occur as a result of cellular [...] Read more.
Adult pancreatic acinar cells show high plasticity allowing them to change in their differentiation commitment. Pancreatic acinar-to-ductal metaplasia (ADM) is a cellular process in which the differentiated pancreatic acinar cells transform into duct-like cells. This process can occur as a result of cellular injury or inflammation in the pancreas. While ADM is a reversible process allowing pancreatic acinar regeneration, persistent inflammation or injury can lead to the development of pancreatic intraepithelial neoplasia (PanIN), which is a common precancerous lesion that precedes pancreatic ductal adenocarcinoma (PDAC). Several factors can contribute to the development of ADM and PanIN, including environmental factors such as obesity, chronic inflammation and genetic mutations. ADM is driven by extrinsic and intrinsic signaling. Here, we review the current knowledge on the cellular and molecular biology of ADM. Understanding the cellular and molecular mechanisms underlying ADM is critical for the development of new therapeutic strategies for pancreatitis and PDAC. Identifying the intermediate states and key molecules that regulate ADM initiation, maintenance and progression may help the development of novel preventive strategies for PDAC. Full article
(This article belongs to the Special Issue Digestive Inflammation and New Therapeutical Targets)
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12 pages, 291 KiB  
Review
Microbiota Composition in Diverticular Disease: Implications for Therapy
by Antonio Tursi, Valerio Papa, Loris Riccardo Lopetuso, Carlo Romano Settanni, Antonio Gasbarrini and Alfredo Papa
Int. J. Mol. Sci. 2022, 23(23), 14799; https://doi.org/10.3390/ijms232314799 - 26 Nov 2022
Cited by 1 | Viewed by 1541
Abstract
Gut microbiota (GM) composition and its imbalance are crucial in the pathogenesis of several diseases, mainly those affecting the gastrointestinal tract. Colon diverticulosis and its clinical manifestations (diverticular disease, DD) are among the most common digestive disorders in developed countries. In recent literature, [...] Read more.
Gut microbiota (GM) composition and its imbalance are crucial in the pathogenesis of several diseases, mainly those affecting the gastrointestinal tract. Colon diverticulosis and its clinical manifestations (diverticular disease, DD) are among the most common digestive disorders in developed countries. In recent literature, the role of GM imbalance in the onset of the different manifestations within the clinical spectrum of DD has been highlighted. This narrative review aims to summarize and critically analyze the current knowledge on GM dysbiosis in diverticulosis and DD by comparing the available data with those found in inflammatory bowel disease (IBD). The rationale for using probiotics to rebalance dysbiosis in DD is also discussed. Full article
(This article belongs to the Special Issue Digestive Inflammation and New Therapeutical Targets)
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