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Drugs in Inflammatory Bowel Diseases
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Drugs in Inflammatory Bowel Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 7732

Special Issue Editors

Dr. Vanessa D’Antongiovanni

E-Mail Website
Guest Editor
Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Interests: inflammatory bowel disease; phytochemicals; prebiotics; probiotics; small molecules; gut–brain axis; enteric glial network; pharmacological approaches; obesity; intestinal organoids
Special Issues, Collections and Topics in MDPI journals
Dr. Carolina Pellegrini

E-Mail Website
Guest Editor
Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Interests: inflammatory bowel diseases; inflammation; intestinal functional disorders; animal models; gut–brain axis; obesity; patients
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammatory bowel diseases (IBDs) make up a group of idiopathic, chronic, relapsing, and inflammatory conditions, which include ulcerative colitis and Crohn’s disease. These disorders are characterized by intestinal symptoms associated with chronic inflammation of the intestinal mucosa, such as gut dysmotility and visceral pain. A common denominator observed in IBD patients is deregulated intestinal mucosa functions, as well as the exuberant activity of immune cell populations. Indeed, it is widely recognized that in genetically susceptible hosts, pathologic immune responses with an imbalanced interaction with luminal microbes compromise the intestinal epithelial barrier, triggering the development of chronic intestinal inflammation.

Currently, the pharmacological management of IBD patients is far from satisfactory. Indeed, the insufficient efficacy and safety of traditional drugs (i.e., corticosteroids, immunosuppressants, and salicylates), as well as recent biotechnological drugs (including anti-TNF and other biologic treatments), have spurred the interest of the scientific community who have sought to identify novel molecular targets for the management of the immune inflammatory components and visceral hypersensitivity associated with IBDs.

On these bases, this Special Issue, entitled “Drugs in Inflammatory Bowel Diseases”, invites researchers to contribute with original research articles, review articles, and short communications related to all aspects of developing new therapeutic agents or therapeutic strategies for the management of IBDs.

Dr. Vanessa D'Antongiovanni
Dr. Carolina Pellegrini
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

  • inflammatory bowel disease
  • molecular target
  • phytochemicals
  • prebiotics
  • probiotics
  • ulcerative colitis
  • Crohn’s disease
  • small molecules
  • therapeutical approaches
  • therapeutic agents

Published Papers (5 papers)

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Research

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19 pages, 3901 KiB  
Article
Enhancement of Radiation Sensitivity by Cathepsin L Suppression in Colon Carcinoma Cells
by Ramadan F. Abdelaziz, Ahmed M. Hussein, Mohamed H. Kotob, Christina Weiss, Krzysztof Chelminski, Tamara Stojanovic, Christian R. Studenik and Mohammed Aufy
Int. J. Mol. Sci. 2023, 24(23), 17106; https://doi.org/10.3390/ijms242317106 - 4 Dec 2023
Cited by 2 | Viewed by 1163
Abstract
Cancer is one of the main causes of death globally. Radiotherapy/Radiation therapy (RT) is one of the most common and effective cancer treatments. RT utilizes high-energy radiation to damage the DNA of cancer cells, leading to their death or impairing their proliferation. However, [...] Read more.
Cancer is one of the main causes of death globally. Radiotherapy/Radiation therapy (RT) is one of the most common and effective cancer treatments. RT utilizes high-energy radiation to damage the DNA of cancer cells, leading to their death or impairing their proliferation. However, radiation resistance remains a significant challenge in cancer treatment, limiting its efficacy. Emerging evidence suggests that cathepsin L (cath L) contributes to radiation resistance through multiple mechanisms. In this study, we investigated the role of cath L, a member of the cysteine cathepsins (caths) in radiation sensitivity, and the potential reduction in radiation resistance by using the specific cath L inhibitor (Z-FY(tBu)DMK) or by knocking out cath L with CRISPR/Cas9 in colon carcinoma cells (caco-2). Cells were treated with different doses of radiation (2, 4, 6, 8, and 10), dose rate 3 Gy/min. In addition, the study conducted protein expression analysis by western blot and immunofluorescence assay, cytotoxicity MTT, and apoptosis assays. The results demonstrated that cath L was upregulated in response to radiation treatment, compared to non-irradiated cells. In addition, inhibiting or knocking out cath L led to increased radiosensitivity in contrast to the negative control group. This may indicate a reduced ability of cancer cells to recover from radiation-induced DNA damage, resulting in enhanced cell death. These findings highlight the possibility of targeting cath L as a therapeutic strategy to enhance the effectiveness of RT. Further studies are needed to elucidate the underlying molecular mechanisms and to assess the translational implications of cath L knockout in clinical settings. Ultimately, these findings may contribute to the development of novel treatment approaches for improving outcomes of RT in cancer patients. Full article
(This article belongs to the Special Issue Drugs in Inflammatory Bowel Diseases)
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12 pages, 2334 KiB  
Article
Long Non-Coding RNA Signatures in the Ileum and Colon of Crohn’s Disease Patients and Effect of Anti-TNF-α Treatment on Their Modulation
by Montse Baldan-Martin, Cristina Rubín de Célix, Macarena Orejudo, Lorena Ortega Moreno, Samuel Fernández-Tomé, Irene Soleto, Cristina Ramirez, Ricardo Arroyo, Paloma Fernández, Cecilio Santander, José Andrés Moreno-Monteagudo, María José Casanova, Fernando Casals, Sergio Casabona, Irene Becerro, Juan J. Lozano, Ana M. Aransay, María Chaparro and Javier P. Gisbert
Int. J. Mol. Sci. 2023, 24(21), 15691; https://doi.org/10.3390/ijms242115691 - 28 Oct 2023
Viewed by 885
Abstract
Biological therapies only benefit one-third of patients with Crohn’s disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in [...] Read more.
Biological therapies only benefit one-third of patients with Crohn’s disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptome. Full article
(This article belongs to the Special Issue Drugs in Inflammatory Bowel Diseases)
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16 pages, 12768 KiB  
Article
Anti-Hyperalgesic Efficacy of Acetyl L-Carnitine (ALCAR) Against Visceral Pain Induced by Colitis: Involvement of Glia in the Enteric and Central Nervous System
by Elena Lucarini, Laura Micheli, Alessandra Toti, Clara Ciampi, Francesco Margiotta, Lorenzo Di Cesare Mannelli and Carla Ghelardini
Int. J. Mol. Sci. 2023, 24(19), 14841; https://doi.org/10.3390/ijms241914841 - 2 Oct 2023
Cited by 1 | Viewed by 1504
Abstract
The management of abdominal pain in patients affected by inflammatory bowel diseases (IBDs) still represents a problem because of the lack of effective treatments. Acetyl L-carnitine (ALCAR) has proved useful in the treatment of different types of chronic pain with excellent tolerability. The [...] Read more.
The management of abdominal pain in patients affected by inflammatory bowel diseases (IBDs) still represents a problem because of the lack of effective treatments. Acetyl L-carnitine (ALCAR) has proved useful in the treatment of different types of chronic pain with excellent tolerability. The present work aimed at evaluating the anti-hyperalgesic efficacy of ALCAR in a model of persistent visceral pain associated with colitis induced by 2,4-dinitrobenzene sulfonic acid (DNBS) injection. Two different protocols were applied. In the preventive protocol, ALCAR was administered daily starting 14 days to 24 h before the delivery of DNBS. In the interventive protocol, ALCAR was daily administered starting the same day of DNBS injection, and the treatment was continued for 14 days. In both cases, ALCAR significantly reduced the establishment of visceral hyperalgesia in DNBS-treated animals, though the interventive protocol showed a greater efficacy than the preventive one. The interventive protocol partially reduced colon damage in rats, counteracting enteric glia and spinal astrocyte activation resulting from colitis, as analyzed by immunofluorescence. On the other hand, the preventive protocol effectively protected enteric neurons from the inflammatory insult. These findings suggest the putative usefulness of ALCAR as a food supplement for patients suffering from IBDs. Full article
(This article belongs to the Special Issue Drugs in Inflammatory Bowel Diseases)
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Review

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19 pages, 2285 KiB  
Review
Pomegranate (Punica granatum L.) and Its Rich Ellagitannins as Potential Inhibitors in Ulcerative Colitis
by Huimin Li, Jingya Ruan, Jiayan Huang, Dingshan Yang, Haiyang Yu, Yuzheng Wu, Yi Zhang and Tao Wang
Int. J. Mol. Sci. 2023, 24(24), 17538; https://doi.org/10.3390/ijms242417538 - 16 Dec 2023
Cited by 2 | Viewed by 1442
Abstract
Ulcerative colitis, an immune-mediated inflammatory disease of the gastrointestinal tract, places a significant financial burden on patients and the healthcare system. Recently, reviews of the pomegranate and the abundant medicinal applications of its ellagitannins, as well as its pharmacological action, phytochemicals, metabolism, and [...] Read more.
Ulcerative colitis, an immune-mediated inflammatory disease of the gastrointestinal tract, places a significant financial burden on patients and the healthcare system. Recently, reviews of the pomegranate and the abundant medicinal applications of its ellagitannins, as well as its pharmacological action, phytochemicals, metabolism, and pharmacokinetics, have been completed. However, summaries on their anti-ulcerative colitis effects are lacking. Numerous preclinical animal investigations and clinical human trial reports demonstrated the specific therapeutic effects of pomegranate and the effect of its ellagitannins against ulcerative colitis. According to the literature collected by Sci-finder and PubMed databases over the past 20 years, this is the first review that has compiled references regarding how the rich ellagitannins found in pomegranate have altered the ulcerative colitis. It was suggested that the various parts of pomegranates and their rich ellagitannins (especially their primary components, punicalagin, and ellagic acid) can inhibit oxidant and inflammatory processes, regulate the intestinal barrier and flora, and provide an anti-ulcerative colitis resource through dietary management. Full article
(This article belongs to the Special Issue Drugs in Inflammatory Bowel Diseases)
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23 pages, 1709 KiB  
Review
Manipulating Microbiota in Inflammatory Bowel Disease Treatment: Clinical and Natural Product Interventions Explored
by Mengjie Zhu, Yijie Song, Yu Xu and Hongxi Xu
Int. J. Mol. Sci. 2023, 24(13), 11004; https://doi.org/10.3390/ijms241311004 - 2 Jul 2023
Cited by 7 | Viewed by 2173
Abstract
Inflammatory bowel disease (IBD) is a complex multifactorial chronic inflammatory disease, that includes Crohn’s disease (CD) and ulcerative colitis (UC), having progressively increasing global incidence. Disturbed intestinal flora has been highlighted as an important feature of IBD and offers promising strategies for IBD [...] Read more.
Inflammatory bowel disease (IBD) is a complex multifactorial chronic inflammatory disease, that includes Crohn’s disease (CD) and ulcerative colitis (UC), having progressively increasing global incidence. Disturbed intestinal flora has been highlighted as an important feature of IBD and offers promising strategies for IBD remedies. A brief overview of the variations occurring in intestinal flora during IBD is presented, and the role of the gut microbiota in intestinal barrier maintenance, immune and metabolic regulation, and the absorption and supply of nutrients is reviewed. More importantly, we review drug research on gut microbiota in the past ten years, including research on clinical and natural drugs, as well as adjuvant therapies, such as Fecal Microbiota Transplantation and probiotic supplements. We also summarize the interventions and mechanisms of these drugs on gut microbiota. Full article
(This article belongs to the Special Issue Drugs in Inflammatory Bowel Diseases)
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