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Pathophysiology in Colonic Diseases
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Pathophysiology in Colonic Diseases

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 (31 October 2020) | Viewed by 70599

Special Issue Editors

Dr. Hirokazu Fukui

E-Mail Website
Guest Editor
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya 663-8501, Japan
Interests: gut microbiome; inflammation; functional gastrointestinal disorders; gut hormone; pathology; carcinogenesis; inflammatory bowel disease; mucosal barrier; immunity; metabolomics
Special Issues, Collections and Topics in MDPI journals
Dr. Jiro Watari

E-Mail
Guest Editor
President, Kinentou Hospital, Sapporo, Japan

Special Issue Information

Dear Colleagues,

This Special Issue “Pathophysiology in Colonic Diseases” of the International Journal of Molecular Sciences (IJMS) will publish contributions on all aspects of molecular pathology. Not only experimental studies but also translational researches are acceptable. As IJMS focuses on deep molecular research, papers only containing clinical trials/data are not acceptable. Although we never reject endoscopic studies, studies regarding the endoscopic techniques and/or images alone are not acceptable. This Special Issue invites submissions regarding various colonic diseases such as colorectal cancer, inflammatory bowel diseases, irritable bowel syndrome, or colonic infectious diseases. We encourage the researchers to publish studies that attempt to clarify the pathophysiological mechanism of those diseases. Particularly, microbiome, intestinal mucosal immunity, gut hormone, and pharmacological aspects are topics of interest.

Dr. Hirokazu Fukui
Dr. Jiro Watari
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 diseases
  • colonic carcinogenesis
  • irritable bowel syndrome
  • gut hormone
  • microbiome
  • intestinal mucosal immunity
  • pharmacology
  • colonic infectious disease
  • molecular pathology
  • genetic and epigenetic mechanisms

Published Papers (15 papers)

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Research

Jump to: Review

17 pages, 5092 KiB  
Article
GLP-2 Prevents Neuronal and Glial Changes in the Distal Colon of Mice Chronically Treated with Cisplatin
by Patrizia Nardini, Alessandro Pini, Anne Bessard, Emilie Duchalais, Elena Niccolai, Michel Neunlist and Maria Giuliana Vannucchi
Int. J. Mol. Sci. 2020, 21(22), 8875; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228875 - 23 Nov 2020
Cited by 15 | Viewed by 2778
Abstract
Cisplatin is a chemotherapeutic agent widely used for the treatment of solid cancers. Its administration is commonly associated with acute and chronic gastrointestinal dysfunctions, likely related to mucosal and enteric nervous system (ENS) injuries, respectively. Glucagon-like peptide-2 (GLP-2) is a pleiotropic hormone exerting [...] Read more.
Cisplatin is a chemotherapeutic agent widely used for the treatment of solid cancers. Its administration is commonly associated with acute and chronic gastrointestinal dysfunctions, likely related to mucosal and enteric nervous system (ENS) injuries, respectively. Glucagon-like peptide-2 (GLP-2) is a pleiotropic hormone exerting trophic/reparative activities on the intestine, via antiapoptotic and pro-proliferating pathways, to guarantee mucosal integrity, energy absorption and motility. Further, it possesses anti-inflammatory properties. Presently, cisplatin acute and chronic damages and GLP-2 protective effects were investigated in the mouse distal colon using histological, immunohistochemical and biochemical techniques. The mice received cisplatin and the degradation-resistant GLP-2 analog ([Gly2]GLP-2) for 4 weeks. Cisplatin-treated mice showed mucosal damage, inflammation, IL-1β and IL-10 increase; decreased number of total neurons, ChAT- and nNOS-immunoreactive (IR) neurons; loss of SOX-10-IR cells and reduced expression of GFAP- and S100β-glial markers in the myenteric plexus. [Gly2]GLP-2 co-treatment partially prevented mucosal damage and counteracted the increase in cytokines and the loss of nNOS-IR and SOX-10-IR cells but not that of ChAT-IR neurons. Our data demonstrate that cisplatin causes mucosal injuries, neuropathy and gliopathy and that [Gly2]GLP-2 prevents these injuries, partially reducing mucosal inflammation and inducing ENS remodeling. Hence, this analog could represent an effective strategy to overcome colonic injures induced by cisplatin. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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17 pages, 4198 KiB  
Article
Leptin Downregulates Angulin-1 in Active Crohn’s Disease via STAT3
by Jia-Chen E. Hu, Christian Bojarski, Federica Branchi, Michael Fromm and Susanne M. Krug
Int. J. Mol. Sci. 2020, 21(21), 7824; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217824 - 22 Oct 2020
Cited by 10 | Viewed by 2314
Abstract
Crohn’s disease (CD) has an altered intestinal barrier function, yet the underlying mechanisms remain to be disclosed. The tricellular tight junction protein tricellulin is involved in the maintenance of the paracellular macromolecule barrier and features an unchanged expression level in CD but a [...] Read more.
Crohn’s disease (CD) has an altered intestinal barrier function, yet the underlying mechanisms remain to be disclosed. The tricellular tight junction protein tricellulin is involved in the maintenance of the paracellular macromolecule barrier and features an unchanged expression level in CD but a shifted localization. As angulins are known to regulate the localization of tricellulin, we hypothesized the involvement of angulins in CD. Using human biopsies, we found angulin-1 was downregulated in active CD compared with both controls and CD in remission. In T84 and Caco-2 monolayers, leptin, a cytokine secreted by fat tissue and affected in CD, decreased angulin-1 expression. This effect was completely blocked by STAT3 inhibitors, Stattic and WP1066, but only partially by JAK2 inhibitor AG490. The effect of leptin was also seen at a functional level as we observed in Caco-2 cells an increased permeability for FITC-dextran 4 kDa indicating an impaired barrier against macromolecule uptake. In conclusion, we were able to show that in active CD angulin-1 expression is downregulated, which leads to increased macromolecule permeability and is inducible by leptin via STAT3. This suggests that angulin-1 and leptin secretion are potential targets for intervention in CD to restore the impaired intestinal barrier. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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15 pages, 1326 KiB  
Communication
Colon Transcriptomics Reveals Sex-Dependent Metabolic Signatures in Response to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Treatment in C57BL/6N Mice
by Jeong Hoon Pan, Cara Cicalo, Brandy Le, Suwon Jeon, Sangyub Kim, Kyung A. Hwang, Byungwhi Kong, Jin Hyup Lee and Jae Kyeom Kim
Int. J. Mol. Sci. 2020, 21(18), 6620; https://doi.org/10.3390/ijms21186620 - 10 Sep 2020
Cited by 1 | Viewed by 2077
Abstract
Diets high in red meats, particularly meats cooked at high temperature, increase the risk of colon cancer due to a production of heterocyclic aromatic amines (HAAs). Of the identified HAAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most mass abundant colon carcinogen in charred meat or [...] Read more.
Diets high in red meats, particularly meats cooked at high temperature, increase the risk of colon cancer due to a production of heterocyclic aromatic amines (HAAs). Of the identified HAAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most mass abundant colon carcinogen in charred meat or fish. Here, we comprehensively examined sex-dependent colon transcriptome signatures in response to PhIP treatment to identify biological discrepancies. Eight-week-old male and female C57BL/6N mice were intraperitoneally injected with PhIP (10 mg/kg of body weight) and colon tissues were harvested 24 h after PhIP injection, followed by colon transcriptomics analysis. A list of differentially expressed genes (DEGs) was utilized for computational bioinformatic analyses. Specifically, overrepresentation test using the Protein Analysis Through Evolutionary Relationships tool was carried out to annotate sex-dependent changes in transcriptome signatures after PhIP treatment. Additionally, the most significantly affected canonical pathways by PhIP treatment were predicted using the Ingenuity Pathway Analysis. As results, male and female mice presented different metabolic signatures in the colon transcriptome. In the male mice, oxidative phosphorylation in the mitochondrial respiratory chain was the pathway impacted the most; this might be due to a shortage of ATP for DNA repair. On the other hand, the female mice showed concurrent activation of lipolysis and adipogenesis. The present study provides the foundational information for future studies of PhIP effects on underlying sex-dependent mechanisms. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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14 pages, 3942 KiB  
Article
Alteration of Colonic Mucosal Permeability during Antibiotic-Induced Dysbiosis
by Ying Ran, Hirokazu Fukui, Xin Xu, Xuan Wang, Nobuhiko Ebisutani, Yoshiki Tanaka, Ayako Maeda, Yutaka Makizaki, Hiroshi Ohno, Takashi Kondo, Tomoaki Kono, Katsuyuki Tozawa, Toshihiko Tomita, Tadayuki Oshima and Hiroto Miwa
Int. J. Mol. Sci. 2020, 21(17), 6108; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176108 - 25 Aug 2020
Cited by 21 | Viewed by 2873
Abstract
Although dysbiosis is likely to disturb the mucosal barrier system, the mechanism involved has remained unclear. Here, we investigated alterations of colonic mucosal permeability and tight junction (TJ) molecules in mice with antibiotic-induced dysbiosis. Mice were orally administered vancomycin or polymyxin B for [...] Read more.
Although dysbiosis is likely to disturb the mucosal barrier system, the mechanism involved has remained unclear. Here, we investigated alterations of colonic mucosal permeability and tight junction (TJ) molecules in mice with antibiotic-induced dysbiosis. Mice were orally administered vancomycin or polymyxin B for 7 days, and then fecal samples were subjected to microbial 16S rRNA analysis. The colonic mucosal permeability was evaluated by chamber assay. The colonic expression of TJ molecules and cytokines was examined by real-time RT-PCR, Western blotting, and immunohistochemistry. Caco2 cells were stimulated with cytokines and their transepithelial electric resistance (TEER) was measured. Vancomycin-treated mice showed significantly lower gut microbiota diversity than controls, and the same tendency was evident in polymyxin B-treated mice. The colonic mucosal permeability was significantly elevated in both vancomycin- and polymyxin B-treated mice. The expression of claudin 4 in the colonic mucosa was decreased in both vancomycin- and polymyxin B-treated mice. Colonic expression of TNF-α and/or IFN-γ was significantly increased in mice that had been administered antibiotics. TNF-α and IFN-γ stimulation dose-dependently decreased TEER in Caco2 cells. Antibiotic-induced dysbiosis is correlated with the enhancement in colonic tissue permeability, accompanied by a reduction in claudin 4 expression and enhancement in TNF-α and/or IFN-γ expression in mice. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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17 pages, 2511 KiB  
Article
Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1
by Keitaro Takahashi, Mikihiro Fujiya, Hiroaki Konishi, Yuki Murakami, Takuya Iwama, Takahiro Sasaki, Takehito Kunogi, Aki Sakatani, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe and Toshikatsu Okumura
Int. J. Mol. Sci. 2020, 21(12), 4514; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124514 - 25 Jun 2020
Cited by 13 | Viewed by 2100
Abstract
The oncogenic properties of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) have been reported, although the tumor-promoting mechanism remains unclear. We herein report the mechanism underlying colorectal cancer cell progression mediated by hnRNP H1. The growth of colorectal cancer cells was suppressed by hnRNP [...] Read more.
The oncogenic properties of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) have been reported, although the tumor-promoting mechanism remains unclear. We herein report the mechanism underlying colorectal cancer cell progression mediated by hnRNP H1. The growth of colorectal cancer cells was suppressed by hnRNP H1 downregulation. A terminal deoxynucleotidyl transferase dUTP nick-end labeling assay revealed the anti-apoptotic effect of hnRNP H1 in colorectal cancer cells. An RNA immunoprecipitation assay revealed that hnRNP H1 bound to sphingosine-1-phosphate lyase 1 (SGPL1). Reverse transcription-polymerase chain reaction revealed the high expression of hnRNP H1 mRNA in colorectal cancer cells and Spearman’s rank correlation coefficient showed a strong positive correlation between hnRNP H1 mRNA and SGPL1 mRNA. An siRNA of hnRNP H1 decreased SGPL1 mRNA expression in colorectal cancer cells, but not in non-tumorous cells. These findings suggested that hnRNP H1 increased SGPL1 mRNA expression specifically in cancer cells through direct binding. Targeted knockdown of hnRNP H1 or SGPL1 with siRNAs upregulated p53 phosphorylation and p53-associated molecules, resulting in cell growth inhibition, while hnRNP H1 upregulated the mRNA of SGPL1 and inhibited p53 activation, thereby promoting tumor cell growth. This is a novel mechanism underlying colorectal cancer cell progression mediated by hnRNP H1–SGPL1 mRNA stabilization. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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14 pages, 3155 KiB  
Article
Monoamine Oxidase B Expression Correlates with a Poor Prognosis in Colorectal Cancer Patients and Is Significantly Associated with Epithelial-to-Mesenchymal Transition-Related Gene Signatures
by Yi-Chieh Yang, Ming-Hsien Chien, Tsung-Ching Lai, Chia-Yi Su, Yi-Hua Jan, Michael Hsiao and Chi-Long Chen
Int. J. Mol. Sci. 2020, 21(8), 2813; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082813 - 17 Apr 2020
Cited by 22 | Viewed by 2928
Abstract
Monoamine oxidases (MAOs) including MAOA and MAOB are enzymes located on the outer membranes of mitochondria, which are responsible for catalyzing monoamine oxidation. Recently, increased level of MAOs were shown in several cancer types. However, possible roles of MAOs have not yet been [...] Read more.
Monoamine oxidases (MAOs) including MAOA and MAOB are enzymes located on the outer membranes of mitochondria, which are responsible for catalyzing monoamine oxidation. Recently, increased level of MAOs were shown in several cancer types. However, possible roles of MAOs have not yet been elucidated in the progression and prognosis of colorectal carcinoma (CRC). We therefore analyzed the importance of MAOs in CRC by an in silico analysis and tissue microarrays. Several independent cohorts indicated that high expression of MAOB, but not MAOA, was correlated with a worse disease stage and poorer survival. In total, 203 colorectal adenocarcinoma cases underwent immunohistochemical staining of MAOs, and associations with clinicopathological parameters and patient outcomes were evaluated. We found that MAOB is highly expressed in CRC tissues compared to normal colorectal tissues, and its expression was significantly correlated with a higher recurrence rate and a poor prognosis. Moreover, according to the univariate and multivariate analyses, we found that MAOB could be an independent prognostic factor for overall survival and disease-free survival, and its prognostic value was better than T and N stage. Furthermore, significant positive and negative correlations of MAOB with mesenchymal-type and epithelial-type gene expressions were observed in CRC tissues. According to the highlighted characteristics of MAOB in CRC, MAOB can be used as a novel indicator to predict the progression and prognosis of CRC patients. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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20 pages, 8382 KiB  
Article
Predominant Distribution of the RNAi Machinery at Apical Adherens Junctions in Colonic Epithelia Is Disrupted in Cancer
by Joyce Nair-Menon, Amanda C. Daulagala, Dean M. Connor, Lauren Rutledge, Trevor Penix, Mary Catherine Bridges, Bridgette Wellslager, Demetri D. Spyropoulos, Cynthia D. Timmers, Ann-Marie Broome and Antonis Kourtidis
Int. J. Mol. Sci. 2020, 21(7), 2559; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072559 - 07 Apr 2020
Cited by 14 | Viewed by 3650
Abstract
The RNA interference (RNAi) machinery is an essential component of the cell, regulating miRNA biogenesis and function. RNAi complexes were thought to localize either in the nucleus, such as the microprocessor, or in the cytoplasm, such as the RNA-induced silencing complex (RISC). We [...] Read more.
The RNA interference (RNAi) machinery is an essential component of the cell, regulating miRNA biogenesis and function. RNAi complexes were thought to localize either in the nucleus, such as the microprocessor, or in the cytoplasm, such as the RNA-induced silencing complex (RISC). We recently revealed that the core microprocessor components DROSHA and DGCR8, as well as the main components of RISC, including Ago2, also associate with the apical adherens junctions of well-differentiated cultured epithelial cells. Here, we demonstrate that the localization of the core RNAi components is specific and predominant at apical areas of cell-cell contact of human normal colon epithelial tissues and normal primary colon epithelial cells. Importantly, the apical junctional localization of RNAi proteins is disrupted or lost in human colon tumors and in poorly differentiated colon cancer cell lines, correlating with the dysregulation of the adherens junction component PLEKHA7. We show that the restoration of PLEKHA7 expression at adherens junctions of aggressively tumorigenic colon cancer cells restores the junctional localization of RNAi components and suppresses cancer cell growth in vitro and in vivo. In summary, this work identifies the apical junctional localization of the RNAi machinery as a key feature of the differentiated colonic epithelium, with a putative tumor suppressing function. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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Review

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22 pages, 1644 KiB  
Review
Role of Inflammation in Pathophysiology of Colonic Disease: An Update
by Noha Ahmed Nasef and Sunali Mehta
Int. J. Mol. Sci. 2020, 21(13), 4748; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21134748 - 03 Jul 2020
Cited by 15 | Viewed by 10740
Abstract
Diseases of the colon are a big health burden in both men and women worldwide ranging from acute infection to cancer. Environmental and genetic factors influence disease onset and outcome in multiple colonic pathologies. The importance of inflammation in the onset, progression and [...] Read more.
Diseases of the colon are a big health burden in both men and women worldwide ranging from acute infection to cancer. Environmental and genetic factors influence disease onset and outcome in multiple colonic pathologies. The importance of inflammation in the onset, progression and outcome of multiple colonic pathologies is gaining more traction as the evidence from recent research is considered. In this review, we provide an update on the literature to understand how genetics, diet, and the gut microbiota influence the crosstalk between immune and non-immune cells resulting in inflammation observed in multiple colonic pathologies. Specifically, we focus on four colonic diseases two of which have a more established association with inflammation (inflammatory bowel disease and colorectal cancer) while the other two have a less understood relationship with inflammation (diverticular disease and irritable bowel syndrome). Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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27 pages, 2954 KiB  
Review
Antioxidant, Anti-Inflammatory, and Microbial-Modulating Activities of Essential Oils: Implications in Colonic Pathophysiology
by Enzo Spisni, Giovannamaria Petrocelli, Veronica Imbesi, Renato Spigarelli, Demetrio Azzinnari, Marco Donati Sarti, Massimo Campieri and Maria Chiara Valerii
Int. J. Mol. Sci. 2020, 21(11), 4152; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21114152 - 10 Jun 2020
Cited by 44 | Viewed by 5380
Abstract
Essential oils (EOs) are a complex mixture of hydrophobic and volatile compounds synthesized from aromatic plants, most of them commonly used in the human diet. In recent years, many studies have analyzed their antimicrobial, antioxidant, anti-inflammatory, immunomodulatory and anticancer properties in vitro and [...] Read more.
Essential oils (EOs) are a complex mixture of hydrophobic and volatile compounds synthesized from aromatic plants, most of them commonly used in the human diet. In recent years, many studies have analyzed their antimicrobial, antioxidant, anti-inflammatory, immunomodulatory and anticancer properties in vitro and on experimentally induced animal models of colitis and colorectal cancer. However, there are still few clinical studies aimed to understand their role in the modulation of the intestinal pathophysiology. Many EOs and some of their molecules have demonstrated their efficacy in inhibiting bacterial, fungi and virus replication and in modulating the inflammatory and oxidative processes that take place in experimental colitis. In addition to this, their antitumor activity against colorectal cancer models makes them extremely interesting compounds for the modulation of the pathophysiology of the large bowel. The characterization of these EOs is made difficult by their complexity and by the different compositions present in the same oil having different geographical origins. This review tries to shift the focus from the EOs to their individual compounds, to expand their possible applications in modulating colon pathophysiology. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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23 pages, 1724 KiB  
Review
Interplay between Cytokine Circuitry and Transcriptional Regulation Shaping Helper T Cell Pathogenicity and Plasticity in Inflammatory Bowel Disease
by Shin-Huei Fu, Ming-Wei Chien, Chao-Yuan Hsu, Yu-Wen Liu and Huey-Kang Sytwu
Int. J. Mol. Sci. 2020, 21(9), 3379; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093379 - 11 May 2020
Cited by 15 | Viewed by 4723
Abstract
Inflammatory bowel disease (IBD) is a chronic disorder manifested as Crohn’s disease (CD) and ulcerative colitis (UC) characterized by intestinal inflammation and involves a dysregulated immune response against commensal microbiota through the activation of CD4 T helper cells. T helper cell differentiation to [...] Read more.
Inflammatory bowel disease (IBD) is a chronic disorder manifested as Crohn’s disease (CD) and ulcerative colitis (UC) characterized by intestinal inflammation and involves a dysregulated immune response against commensal microbiota through the activation of CD4 T helper cells. T helper cell differentiation to effector or regulatory phenotypes is controlled by cytokine networks and transcriptional regulators. Distinct polarized T helper cells are able to alter their phenotypes to adapt to diverse and fluctuating physiological environments. T helper cells exhibit intrinsic instability and flexibility to express cytokines of other lineages or transdifferentiate from one T helper cell type to another in response to various perturbations from physiological cytokine milieu as a means of promoting local immunity in response to injury or ensure tissue homeostasis. Furthermore, functional plasticity and diversity of T helper cells are associated with pathogenicity and are critical for immune homeostasis and prevention of autoimmunity. In this review, we provide deeper insights into the combinatorial extrinsic and intrinsic signals that control plasticity and transdifferentiation of T helper cells and also highlight the potential of exploiting the genetic reprogramming plasticity of T helper cells in the treatment of IBD. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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17 pages, 1254 KiB  
Review
Post-Translational Modifications of Transcription Factors Harnessing the Etiology and Pathophysiology in Colonic Diseases
by Chao-Yuan Hsu, Shin-Huei Fu, Ming-Wei Chien, Yu-Wen Liu, Shyi-Jou Chen and Huey-Kang Sytwu
Int. J. Mol. Sci. 2020, 21(9), 3207; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093207 - 01 May 2020
Cited by 11 | Viewed by 2988
Abstract
Defects in mucosal immune balance can lead to colonic diseases such as inflammatory bowel diseases and colorectal cancer. With the advancement of understanding for the immunological and molecular basis of colonic disease, therapies targeting transcription factors have become a potential approach for the [...] Read more.
Defects in mucosal immune balance can lead to colonic diseases such as inflammatory bowel diseases and colorectal cancer. With the advancement of understanding for the immunological and molecular basis of colonic disease, therapies targeting transcription factors have become a potential approach for the treatment of colonic disease. To date, the biomedical significance of unique post-translational modifications on transcription factors has been identified, including phosphorylation, methylation, acetylation, ubiquitination, SUMOylation, and O-GlcNAcylation. This review focuses on our current understanding and the emerging evidence of how post-translational regulations modify transcription factors involved in the etiology and pathophysiology of colonic disease as well as the implications of these findings for new therapeutic approaches in these disorders. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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12 pages, 1601 KiB  
Review
Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis
by Takehiro Hirano, Daisuke Hirayama, Kohei Wagatsuma, Tsukasa Yamakawa, Yoshihiro Yokoyama and Hiroshi Nakase
Int. J. Mol. Sci. 2020, 21(9), 3062; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093062 - 26 Apr 2020
Cited by 68 | Viewed by 6165
Abstract
Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor [...] Read more.
Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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21 pages, 664 KiB  
Review
Gut Microbiota beyond Bacteria—Mycobiome, Virome, Archaeome, and Eukaryotic Parasites in IBD
by Mario Matijašić, Tomislav Meštrović, Hana Čipčić Paljetak, Mihaela Perić, Anja Barešić and Donatella Verbanac
Int. J. Mol. Sci. 2020, 21(8), 2668; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082668 - 11 Apr 2020
Cited by 122 | Viewed by 9915
Abstract
The human microbiota is a diverse microbial ecosystem associated with many beneficial physiological functions as well as numerous disease etiologies. Dominated by bacteria, the microbiota also includes commensal populations of fungi, viruses, archaea, and protists. Unlike bacterial microbiota, which was extensively studied in [...] Read more.
The human microbiota is a diverse microbial ecosystem associated with many beneficial physiological functions as well as numerous disease etiologies. Dominated by bacteria, the microbiota also includes commensal populations of fungi, viruses, archaea, and protists. Unlike bacterial microbiota, which was extensively studied in the past two decades, these non-bacterial microorganisms, their functional roles, and their interaction with one another or with host immune system have not been as widely explored. This review covers the recent findings on the non-bacterial communities of the human gastrointestinal microbiota and their involvement in health and disease, with particular focus on the pathophysiology of inflammatory bowel disease. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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14 pages, 1188 KiB  
Review
Potential Use of Biotherapeutic Bacteria to Target Colorectal Cancer-Associated Taxa
by Garreth W. Lawrence, Máire Begley, Paul D. Cotter and Caitriona M. Guinane
Int. J. Mol. Sci. 2020, 21(3), 924; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030924 - 30 Jan 2020
Cited by 18 | Viewed by 5211
Abstract
The role of the gut microbiome in human health and disease is the focus of much attention. It has been widely agreed upon that our gut bacteria play a role in host immunity, nutrient absorption, digestion, metabolism, and other key drivers of health. [...] Read more.
The role of the gut microbiome in human health and disease is the focus of much attention. It has been widely agreed upon that our gut bacteria play a role in host immunity, nutrient absorption, digestion, metabolism, and other key drivers of health. Furthermore, certain microbial signatures and specific taxa have also been associated with the development of diseases, such as obesity; inflammatory bowel disease; and, indeed, colorectal cancer (CRC), which is the focus of this review. By extension, such taxa represent potential therapeutic targets. In particular, the emerging human pathogen Fusobacterium nucleatum represents an important agent in CRC development and its control within the gastrointestinal tract is desirable. This paper reviews the principal bacterial pathogens that have been associated with CRC to date and discusses the in vitro and human studies that have shown the potential use of biotherapeutic strains as a means of targeting CRC-associated bacteria. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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17 pages, 3141 KiB  
Review
Exosomes for Diagnosis and Therapy in Gastrointestinal Cancers
by Maria Principia Scavo, Nicoletta Depalo, Valeria Tutino, Valentina De Nunzio, Chiara Ingrosso, Federica Rizzi, Maria Notarnicola, Maria Lucia Curri and Gianluigi Giannelli
Int. J. Mol. Sci. 2020, 21(1), 367; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010367 - 06 Jan 2020
Cited by 28 | Viewed by 6059
Abstract
Exosomes are membrane-bound extracellular vesicles (EVs) released by most cells, having a size ranging from 30 to 150 nm, and are involved in mechanisms of cell-cell communication in physiological and pathological tissues. Exosomes are engaged in the transport of biomolecules, such as lipids, [...] Read more.
Exosomes are membrane-bound extracellular vesicles (EVs) released by most cells, having a size ranging from 30 to 150 nm, and are involved in mechanisms of cell-cell communication in physiological and pathological tissues. Exosomes are engaged in the transport of biomolecules, such as lipids, proteins, messenger RNAs, and microRNA, and in signal transmission through the intercellular transfer of components. In the context of proteins and nucleic acids transported from exosomes, our interest is focused on the Frizzled proteins family and related messenger RNA. Exosomes can regenerate stem cell phenotypes and convert them into cancer stem cells by regulating the Wnt pathway receptor family, namely Frizzled proteins. In particular, for gastrointestinal cancers, the Frizzled protein involved in those mechanisms is Frizzled-10 (FZD-10). Currently, increasing attention is being devoted to the protein and lipid composition of exosomes interior and membranes, representing profound knowledge of specific exosomes composition fundamental for their application as new delivering drug tools for cancer therapy. This review intends to cover the most recent literature on the use of exosome vesicles for early diagnosis, follow-up, and the use of these physiological nanovectors as drug delivery systems for gastrointestinal cancer therapy. Full article
(This article belongs to the Special Issue Pathophysiology in Colonic Diseases)
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