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Focus on Gastrointestinal Diseases 2.0: Inflammation

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 March 2023) | Viewed by 33749

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Guest Editor
Emergency Anesthesiological and Reanimation Sciences, Fondazione Policlinico Universitario A. Gemelli, 00168 Roma, Italy
Interests: short stay unit; infection, sepsis; trauma; syncope; pulmonary embolism; inflammatory bowel disease; gastroenteritis; gastrointestinal bleeding; diverticulitis
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Special Issue Information

Dear Colleagues,

Gastrointestinal diseases are common, multifactorial pathologies associated with specific genetic, infective, environmental, and host factors. The study of the molecular mechanisms underlying the interaction among these factors is essential to understand the pathophysiology of gastrointestinal diseases and to develop new therapies. These are extremely common diseases in the general population, with a high cost for health systems around the world. The emerging roles of the intestinal microbiome and of local and general immune factors are transforming our inderstanding of gastrointestinal diseases. The identification of molecular mechanisms involved in their development has also generated considerable progress in the therapeutic field in the last 20 years: the use of biological drugs that have changed the natural course of inflammatory bowel diseases is a clear example of this. The molecular characterization of the interactions between external pathogens, such as Helicobacter pylori and the host can also help to decipher the mechanisms that induce inflammatory processes of the mucosa and mutations that can predispose an individual to the onset of gastrointestinal cancers.

As volume 1 of Special Issue “Focus on gastrointestinal diseases ” is successful we reopen this issue again in the /International Journal of Molecular Sciences/ (https://www.mdpi.com/journal/ijms, ISSN 1422-0067, IF 5.923, JCR Category Q1). This second Special Issue, we invite all interested researchers to contribute with original research articles or literature reviews on all aspects related to the molecular mechanisms involved in pathologies of the gastrointestinal system, with particular interest in, but not limited to, inflammatory intestinal, pancreatic, and gastric diseases, further more, more inflammation content will be highly welcomed.

Dr. Marcello Candelli
Guest Editor

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Keywords

  • signal transduction
  • receptor signaling
  • infection and inflammation
  • protein interaction
  • tumor biology
  • growth factors
  • cytokines
  • cell death and differentiation
  • inflammation

Published Papers (13 papers)

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Editorial

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3 pages, 183 KiB  
Editorial
New Advances in Gastroenterology: The Crucial Role of Molecular Medicine
by Marcello Candelli and Francesco Franceschi
Int. J. Mol. Sci. 2023, 24(19), 14907; https://doi.org/10.3390/ijms241914907 - 5 Oct 2023
Viewed by 1146
Abstract
The significant progress we have recently observed in the field of gastroenterology, both in the understanding of pathophysiological mechanisms and in the diagnosis and treatment of diseases, is closely related to the improvement and discovery of new biomolecular techniques [...] Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)

Research

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15 pages, 2871 KiB  
Article
Using Normalized Carcinoembryonic Antigen and Carbohydrate Antigen 19 to Predict and Monitor the Efficacy of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer
by Xiao-Huan Tang, Xiao-Long Wu, Xue-Jun Gan, Yi-Ding Wang, Fang-Zhou Jia, Yi-Xue Wang, Yan Zhang, Xiang-Yu Gao and Zi-Yu Li
Int. J. Mol. Sci. 2023, 24(15), 12192; https://doi.org/10.3390/ijms241512192 - 29 Jul 2023
Cited by 3 | Viewed by 1471
Abstract
Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. Methods: We conducted a retrospective analysis to determine values of [...] Read more.
Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. Methods: We conducted a retrospective analysis to determine values of CEA and CA19-9 prior to NACT (pre-NACT) and after NACT (post-NACT) in 399 patients with locally advanced gastric cancer (LAGC) who received intended NACT and surgery. Results: Among the 399 patients who underwent NACT plus surgery, 132 patients (33.1%) had elevated pre-NACT CEA/CA19-9 values. Furthermore, either pre-NACT or post-NACT CEA /CA19-9 levels were significantly associated with prognosis (p = 0.0023) compared to patients with non-elevated levels. Moreover, among the patients, a significant proportion (73/132, 55.3%) achieved normalized CEA/CA19-9 following NACT, which is a strong marker of a favorable treatment response and survival benefits. In addition, the patients with normalized CEA/CA19-9 also had a prolonged survival compared to those who underwent surgery first (p = 0.0140), which may be attributed to the clearance of micro-metastatic foci. Additionally, the magnitude of CEA/CA19-9 changes did not exhibit a statistically significant prognostic value. Conclusions: Normalization of CEA/CA19-9 is a strong biomarker for the effectiveness of treatment, and can thus be exploited to prolong the long-term survival of patients with LAGC. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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16 pages, 2969 KiB  
Article
Artesunate Dry Emulsion Formulation Combined with Antibiotics for Treatment of Helicobacter pylori Infections: In Vitro/In Vivo Evaluation
by Canh Le-Tien, Lindsay Blemur and Dennis Baltzis
Int. J. Mol. Sci. 2023, 24(13), 11008; https://doi.org/10.3390/ijms241311008 - 2 Jul 2023
Cited by 1 | Viewed by 1562
Abstract
Helicobacter pylori is the primary pathogen responsible for causing gastroduodenal ulcers and stomach cancer. The standard treatment for H. pylori typically involves a combination of antibiotics and acid-reducing medications. However, the recurrence of ulcers is closely linked to the emergence of antibiotic resistance [...] Read more.
Helicobacter pylori is the primary pathogen responsible for causing gastroduodenal ulcers and stomach cancer. The standard treatment for H. pylori typically involves a combination of antibiotics and acid-reducing medications. However, the recurrence of ulcers is closely linked to the emergence of antibiotic resistance in H. pylori, necessitating the development of alternative drugs. This report focuses on the investigation of artesunate as a potential alternative to reduce antibiotic use and enhance effectiveness against H. pylori. Unfortunately, commercial artesunate is available in an acid form, which has poor solubility, especially in gastric acid fluid. The aim of this study is to utilize a water-soluble formulation of artesunate called dry emulsion formulation (ADEF) and combine it with amoxicillin to eradicate H. pylori. In vitro studies were conducted to evaluate the activity of ADEF against H. pylori and determine its inhibitory concentrations. In addition, pharmacokinetic parameters of orally administered ADEF and native artesunate were investigated in rats for in vivo studies. The results showed that when combined with amoxicillin and pantoprazole, ADEF exhibited effectiveness against H. pylori. It is worth noting that the solubility of ADEF in gastric acid appears to be a critical factor for achieving successful treatment. Consequently, ADEF could be considered a promising candidate for H. pylori therapy. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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11 pages, 895 KiB  
Article
Diagnostic Accuracy of Leucine-Rich α-2-Glycoprotein 1 as a Non-Invasive Salivary Biomarker in Pediatric Appendicitis
by Goran Tintor, Miro Jukić, Daniela Šupe-Domić, Ana Jerončić and Zenon Pogorelić
Int. J. Mol. Sci. 2023, 24(7), 6043; https://doi.org/10.3390/ijms24076043 - 23 Mar 2023
Cited by 6 | Viewed by 1590
Abstract
The aim of this study is to evaluate the diagnostic accuracy of leucine-rich α-2-glycoprotein 1 (LRG1) in saliva as a novel biomarker for acute appendicitis in the pediatric population. From October 2021 to June 2022, 92 children aged 5 to 17 years who [...] Read more.
The aim of this study is to evaluate the diagnostic accuracy of leucine-rich α-2-glycoprotein 1 (LRG1) in saliva as a novel biomarker for acute appendicitis in the pediatric population. From October 2021 to June 2022, 92 children aged 5 to 17 years who presented with acute abdomen and suspected acute appendicitis were enrolled in this prospective study. The parameters documented included demographic and clinical information, as well as operative and postoperative data. Patients were divided into two groups: those with acute appendicitis who underwent laparoscopic appendectomy (n = 46) and those without appendicitis (n = 46). The total white blood cell (WBC) count, percent of neutrophils, C-reactive protein (CRP) level, and salivary LRG1 were compared between groups. A commercially available enzyme-linked immunosorbent assay (ELISA) LRG kit was used to measure the LRG levels. The median salivary LRG1 level was significantly higher in the group of children with pathohistologically confirmed acute appendicitis compared to the control group: 233.45 ng/mL (IQR 114.9, 531.2) vs. 55.95 ng/mL (IQR 51.5, 117.9), p < 0.001. LRG1 had an overall good receiver-operator characteristic area under the curve of 0.85 (95% CI 0.76–0.92; p < 0.001). The optimal LRG1 cutoff with best separation between acute appendicitis and the controls was >352.6 ng/mL (95% CI from >270.7 to >352.6). Although the specificity was 100% at this cutoff, the sensitivity for identifying appendicitis was 36%. In addition, a significant difference was found between groups in the laboratory values of all inflammatory markers tested: WBC, absolute neutrophil count, and CRP (p < 0.001 for all). Although LRG1 in saliva showed a good AUC parameter and significantly higher values in patients with acute appendicitis compared to the controls, its usefulness in the patient population who present at emergency departments with abdominal pain is debatable. Future studies should focus on investigating its diagnostic potential. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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16 pages, 4832 KiB  
Article
Development of Highly Sensitive Digital Droplet PCR for Detection of cKIT Mutations in Circulating Free DNA That Mediate Resistance to TKI Treatment for Gastrointestinal Stromal Tumor (GIST)
by Michael Rassner, Silvia Waldeck, Marie Follo, Stefanie Jilg, Ulrike Philipp, Martina Jolic, Julius Wehrle, Philipp J. Jost, Christian Peschel, Anna Lena Illert, Justus Duyster, Florian Scherer and Nikolas von Bubnoff
Int. J. Mol. Sci. 2023, 24(6), 5411; https://doi.org/10.3390/ijms24065411 - 12 Mar 2023
Cited by 2 | Viewed by 1672
Abstract
Background: Mutations in cKIT or PDGFRA are found in up to 90% of patients with gastrointestinal stromal tumors (GISTs). Previously, we described the design, validation, and clinical performance of a digital droplet (dd)PCR assay panel for the detection of imatinib-sensitive cKIT and PDFGRA [...] Read more.
Background: Mutations in cKIT or PDGFRA are found in up to 90% of patients with gastrointestinal stromal tumors (GISTs). Previously, we described the design, validation, and clinical performance of a digital droplet (dd)PCR assay panel for the detection of imatinib-sensitive cKIT and PDFGRA mutations in circulating tumor (ct)DNA. In this study, we developed and validated a set of ddPCR assays for the detection of cKIT mutations mediating resistance to cKIT kinase inhibitors in ctDNA. In addition, we cross-validated these assays using next generation sequencing (NGS). Methods: We designed and validated five new ddPCR assays to cover the most frequent cKIT mutations mediating imatinib resistance in GISTs. For the most abundant imatinib-resistance-mediating mutations in exon 17, a drop-off, probe-based assay was designed. Dilution series (of decreasing mutant (MUT) allele frequency spiked into wildtype DNA) were conducted to determine the limit of detection (LoD). Empty controls, single wildtype controls, and samples from healthy individuals were tested to assess specificity and limit of blank (LoB). For clinical validation, we measured cKIT mutations in three patients and validated results using NGS. Results: Technical validation demonstrated good analytical sensitivity, with a LoD ranging between 0.006% and 0.16% and a LoB ranging from 2.5 to 6.7 MUT fragments/mL. When the ddPCR assays were applied to three patients, the abundance of ctDNA in serial plasma samples reflected the individual disease course, detected disease activity, and indicated resistance mutations before imaging indicated progression. Digital droplet PCR showed good correlation to NGS for individual mutations, with a higher sensitivity of detection. Conclusions: This set of ddPCR assays, together with our previous set of cKIT and PDGFRA mutations assays, allows for dynamic monitoring of cKIT and PDGFRA mutations during treatment. Together with NGS, the GIST ddPCR panel will complement imaging of GISTs for early response evaluation and early detection of relapse, and thus it might facilitate personalized decision-making. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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13 pages, 1883 KiB  
Article
Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins
by Alexandra A. Livanova, Arina A. Fedorova, Alexander V. Zavirsky, Igor I. Krivoi and Alexander G. Markov
Int. J. Mol. Sci. 2023, 24(2), 1753; https://doi.org/10.3390/ijms24021753 - 16 Jan 2023
Cited by 3 | Viewed by 1643
Abstract
The damaging effect of ionizing radiation (IR) exposure results in the disturbance of the gut natural barrier, followed by the development of severe gastrointestinal injury. However, the dose and application segment are known to determine the effects of IR. In this study, we [...] Read more.
The damaging effect of ionizing radiation (IR) exposure results in the disturbance of the gut natural barrier, followed by the development of severe gastrointestinal injury. However, the dose and application segment are known to determine the effects of IR. In this study, we demonstrated the dose- and segment-specificity of tight junction (TJ) alteration in IR-induced gastrointestinal injury in rats. Male Wistar rats were subjected to a total-body X-ray irradiation at doses of 2 or 10 Gy. Isolated jejunum and colon segments were tested in an Ussing chamber 72 h after exposure. In the jejunum, 10-Gy IR dramatically altered transepithelial resistance, short-circuit current and permeability for sodium fluorescein. These changes were accompanied by severe disturbance of histological structure and total rearrangement of TJ content (increased content of claudin-1, -2, -3 and -4; multidirectional changes in tricellulin and occludin). In the colon of 10-Gy irradiated rats, lesions of barrier and transport functions were less pronounced, with only claudin-2 and -4 altered among TJ proteins. The 2-Gy IR did not change electrophysiological characteristics or permeability in the colon or jejunum, although slight alterations in jejunum histology were noted, emphasized with claudin-3 increase. Considering that TJ proteins are critical for maintaining epithelial barrier integrity, these findings may have implications for countermeasures in gastrointestinal acute radiation injury. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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15 pages, 5875 KiB  
Article
Alpha-1 Antitrypsin Inhibits Tumorigenesis and Progression of Colitis-Associated Colon Cancer through Suppression of Inflammatory Neutrophil-Activated Serine Proteases and IGFBP-3 Proteolysis
by Qing Cai, Minsun Kim, Aki Harada, Michael O. Idowu, Gobalakrishnan Sundaresan, Jamal Zweit and Youngman Oh
Int. J. Mol. Sci. 2022, 23(22), 13737; https://doi.org/10.3390/ijms232213737 - 8 Nov 2022
Cited by 4 | Viewed by 1853
Abstract
Colitis-associated colon cancer (CAC) accompanies the massive infiltration of neutrophils during tumorigenesis and progression of CAC. Depletion of neutrophils in circulation results in significant inhibition of tumor incidence in CAC. However, the underlying mechanisms are largely unclear. In this study, we provide evidence [...] Read more.
Colitis-associated colon cancer (CAC) accompanies the massive infiltration of neutrophils during tumorigenesis and progression of CAC. Depletion of neutrophils in circulation results in significant inhibition of tumor incidence in CAC. However, the underlying mechanisms are largely unclear. In this study, we provide evidence for the crucial involvement of inflammatory neutrophil-activated serine proteases (NSPs) on the dysregulation of the anti-inflammatory and antitumor IGFBP-3/IGFBP-3R signaling axis in CAC using a chronic AOM/DSS mouse model. We also provide preclinical evidence for α1-antitrypsin (AAT) as a preventive and as a therapeutic for CAC. AAT administration not only prevented colitis-associated tumorigenesis but also inhibited established CAC. AOM/DSS treatment results in the significant activation of NSPs, leading to CAC through increased pro-inflammatory cytokines and decreased anti-inflammatory and antitumor IGFBP-3. Collectively, these data suggest that the NSPs proteolyze IGFBP-3, whereas AAT inhibits chronic colonic inflammation-induced NSP activity and subsequently suppresses IGFBP-3 proteolysis. Therefore, the anti-inflammatory and antitumor functions of the IGFBP-3/IGFBP-3R axis are restored. AAT mimicking small peptides also showed their inhibitory effects on NSP-induced IGFBP-3 proteolysis. These results suggest that targeting the NSP-IGFBP-3/IGFBP-3R axis using NSP inhibitors such as AAT and the AAT mimics and IGFBP-3R agonists could lead to novel approaches for the prevention and treatment of CAC. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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15 pages, 3642 KiB  
Article
Identification of SLC15A4/PHT1 Gene Products Upregulation Marking the Intestinal Epithelial Monolayer of Ulcerative Colitis Patients
by Aurora Mazzei, Grazia Serino, Alessandro Romano, Emanuele Piccinno, Viviana Scalavino, Anna Maria Valentini, Raffaele Armentano, Roberta Schiavone, Gianluigi Giannelli, Tiziano Verri and Amilcare Barca
Int. J. Mol. Sci. 2022, 23(21), 13170; https://doi.org/10.3390/ijms232113170 - 29 Oct 2022
Cited by 1 | Viewed by 1680
Abstract
SLC15A4/PHT1 is an endolysosome-resident carrier of oligopeptides and histidine recently come into view as a key path marker of immune/autoimmune/inflammatory pathways in immune cells. Yet, its emerging role in inflammatory processes directly targeting the gastrointestinal epithelial layer, as in the multifactorial pathophysiology of [...] Read more.
SLC15A4/PHT1 is an endolysosome-resident carrier of oligopeptides and histidine recently come into view as a key path marker of immune/autoimmune/inflammatory pathways in immune cells. Yet, its emerging role in inflammatory processes directly targeting the gastrointestinal epithelial layer, as in the multifactorial pathophysiology of inflammatory bowel disease (IBD), is poorly investigated. Here, the first identification of SLC15A4/PHT1 gene products in human colonic epithelium of ulcerative colitis (UC) patients is reported, showing protein primarily localized in intracellular vesicle-like compartments. Qualitative and quantitative immunohistochemical analyses of colon biopsies revealed overexpression of SLC15A4/PHT1 protein product in the epithelial layer of UC patients. Results were successfully mirrored in vitro, in spontaneously differentiated enterocyte-like monolayers of Caco-2 cells specifically exposed to DSS (dextran sodium sulphate) to mimic IBD inflammatory onsets. SLC15A4/PHT1 expression and cellular localization were characterized confirming its (dys)regulation traits in inflamed vs. healthy epithelia, strongly hinting the hypothesis of SLC15A4/PHT1 increased function associated with epithelial inflammation in IBD patients. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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18 pages, 2558 KiB  
Article
Dysregulation of miR-1-3p: An Early Event in Colitis-Associated Dysplasia
by Mariana F. Fragoso, Geysson J. Fernandez, Lisa Vanderveer, Harry S. Cooper, Michael Slifker and Margie L. Clapper
Int. J. Mol. Sci. 2022, 23(21), 13024; https://doi.org/10.3390/ijms232113024 - 27 Oct 2022
Cited by 1 | Viewed by 1667
Abstract
Detection of colorectal dysplasia during surveillance colonoscopy remains the best method of determining risk for colitis-associated colorectal cancer (CAC). miRNAs (miRs) show great promise as tissue-specific biomarkers of neoplasia. The goal of this study was to explore the miR expression profile of precancerous [...] Read more.
Detection of colorectal dysplasia during surveillance colonoscopy remains the best method of determining risk for colitis-associated colorectal cancer (CAC). miRNAs (miRs) show great promise as tissue-specific biomarkers of neoplasia. The goal of this study was to explore the miR expression profile of precancerous dysplastic lesions in the AOM/DSS mouse model and identify early molecular changes associated with CAC. Epithelial cells were laser-microdissected from the colonic mucosa (inflamed versus dysplastic) of mice with AOM/DSS-induced colitis. A miR signature that can distinguish inflamed non-neoplastic mucosa from dysplasia was identified. Bioinformatic analyses led to the discovery of associated miR gene targets and enriched pathways and supported the construction of a network interaction map. miR-1a-3p was one of the miRs with the highest number of predicted targets, including Cdk6. Interestingly, miR-1a-3p and Cdk6 were down- and up-regulated in dysplastic lesions, respectively. Transfection of HCT116 and RKO cells with miR-1a-3p mimics induced apoptosis and cell cycle arrest in G1, suggesting its biological function. A slight reduction in the level of CDK6 transcripts was also observed in cells transfected with miR-1. These data provide novel insight into the early molecular alterations that accompany the development of CAC and identify a miR signature that represents a promising biomarker for the early detection of colitis-associated dysplasia. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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13 pages, 3734 KiB  
Article
P-Selectin is a Critical Factor for Platelet-Mediated Protection on Restraint Stress-Induced Gastrointestinal Injury in Mice
by Subhashree Pethaperumal, Shih-Che Hung, Te-Sheng Lien, Der-Shan Sun and Hsin-Hou Chang
Int. J. Mol. Sci. 2022, 23(19), 11909; https://doi.org/10.3390/ijms231911909 - 7 Oct 2022
Cited by 4 | Viewed by 1614
Abstract
Psychological stress is associated with increased risk of gastrointestinal (GI) tract diseases. Evidence indicated that platelets facilitate GI tissue repair in intestinal anastomosis models. However, whether platelets are involved in native mechanism of the rescue of stress-induced GI injury for maintaining the GI [...] Read more.
Psychological stress is associated with increased risk of gastrointestinal (GI) tract diseases. Evidence indicated that platelets facilitate GI tissue repair in intestinal anastomosis models. However, whether platelets are involved in native mechanism of the rescue of stress-induced GI injury for maintaining the GI homeostasis remains elusive. Because P-selectin-deficient (Selp−/) mice displayed higher stress-induced GI injury compared to the wild-type (Selp+/+) mice, and P-selectin is specifically expressed in platelets, we hypothesize that P-selectin-expressing platelets play a protective role in the rescue of stress-induced GI injury. Our goal is to clarify the putative protective role of platelets in a GI system, thereby develop a feasible intervention strategy, such as platelet transfer, to overcome stress-induced GI injury. Through monitoring the plasma levels of GI-nonabsorbable Evans blue dye to reveal the progression course of GI injury in live mice, we found that intravenous treatments of purified platelets ameliorated stress-induced GI leakage. The transfer of platelets from wild-type mice was more potent than from Selp−/ mice in the rescue of stress-induced-GI leakage in the recipients. As such, platelet transfer-mediated rescue was conducted in a P-selectin dependent manner. Additionally, platelet-mediated protection is associated with corrections of stress-induced aberrant GI mRNA expressions, including tight junctions claudin 3 and occludin, as well as stress-induced genes activating transcription factor 3 and AMP-activated protein kinase, after the transfer of wild-type platelets into wild-type and Selp−/ mice. Furthermore, the stress-induced apoptosis of CD326+ GI epithelial cells was rescued by the transfer of wild type, but not P-selectin-deficient platelets. These results suggest that platelet plays a protective role for maintaining the GI homeostasis during stress in vivo, and that P-selectin is a molecular target for managing stress-induced GI tract injury. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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14 pages, 2628 KiB  
Article
Psychological Stress Exacerbates Inflammation of the Ileum via the Corticotropin-Releasing Hormone-Mast Cell Axis in a Mouse Model of Eosinophilic Enteritis
by Atsushi Kanamori, Fumio Tanaka, Masaki Ominami, Yuji Nadatani, Shusei Fukunaga, Koji Otani, Shuhei Hosomi, Noriko Kamata, Yasuaki Nagami, Koichi Taira and Yasuhiro Fujiwara
Int. J. Mol. Sci. 2022, 23(15), 8538; https://doi.org/10.3390/ijms23158538 - 1 Aug 2022
Cited by 4 | Viewed by 1925
Abstract
The effects of psychological stress on eosinophilic gastrointestinal disorders have not been elucidated. This study investigated the effects of psychological stress in a mouse model of eosinophilic enteritis (EoN). BALB/c mice were treated with ovalbumin (OVA) to create an EoN model and subjected [...] Read more.
The effects of psychological stress on eosinophilic gastrointestinal disorders have not been elucidated. This study investigated the effects of psychological stress in a mouse model of eosinophilic enteritis (EoN). BALB/c mice were treated with ovalbumin (OVA) to create an EoN model and subjected to either water avoidance stress (WAS) or sham stress (SS). Microscopic inflammation, eosinophil and mast cell counts, mRNA expression, and protein levels of type 2 helper T cell (Th2) cytokines in the ileum were compared between groups. We evaluated ex vivo intestinal permeability using an Ussing chamber. A corticotropin-releasing hormone type 1 receptor (CRH-R1) antagonist was administered before WAS, and its effects were analyzed. WAS significantly increased diarrhea occurrence and, eosinophil and mast cell counts, and decreased the villus/crypt ratio compared to those in the SS group. The mRNA expression of CRH, interleukin IL-4, IL-5, IL-13, eotaxin-1, and mast cell tryptase β2 significantly increased, and the protein levels of IL-5, IL-13, and OVA-specific immunoglobulin E (IgE) also significantly increased in the WAS group. Moreover, WAS significantly increased the intestinal permeability. The CRH-R1 antagonist significantly inhibited all changes induced by WAS. Psychological stress exacerbated ileal inflammation via the CRH-mast cell axis in an EoN mouse model. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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Review

Jump to: Editorial, Research

14 pages, 1016 KiB  
Review
Helicobacter pylori and Gastric Cancer: Pathogenetic Mechanisms
by Silvia Salvatori, Irene Marafini, Federica Laudisi, Giovanni Monteleone and Carmine Stolfi
Int. J. Mol. Sci. 2023, 24(3), 2895; https://doi.org/10.3390/ijms24032895 - 2 Feb 2023
Cited by 40 | Viewed by 8147
Abstract
Gastric cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide. Helicobacter pylori (H. pylori) is one of the main risk factors for this type of neoplasia. Carcinogenetic mechanisms associated with H. pylori are [...] Read more.
Gastric cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide. Helicobacter pylori (H. pylori) is one of the main risk factors for this type of neoplasia. Carcinogenetic mechanisms associated with H. pylori are based, on the one hand, on the onset of chronic inflammation and, on the other hand, on bacterial-specific virulence factors that can damage the DNA of gastric epithelial cells and promote genomic instability. Here, we review and discuss the major pathogenetic mechanisms by which H. pylori infection contributes to the onset and development of gastric cancer. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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18 pages, 808 KiB  
Review
Autoimmune Pancreatitis: From Pathogenesis to Treatment
by Enrico Celestino Nista, Sara Sofia De Lucia, Vittoria Manilla, Tommaso Schepis, Antonio Pellegrino, Veronica Ojetti, Giulia Pignataro, Lorenzo Zileri dal Verme, Francesco Franceschi, Antonio Gasbarrini and Marcello Candelli
Int. J. Mol. Sci. 2022, 23(20), 12667; https://doi.org/10.3390/ijms232012667 - 21 Oct 2022
Cited by 11 | Viewed by 6832
Abstract
Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological, serological, and pathological findings. Two different types of AIP have been identified: autoimmune pancreatitis type 1 (AIP-1), which is [...] Read more.
Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological, serological, and pathological findings. Two different types of AIP have been identified: autoimmune pancreatitis type 1 (AIP-1), which is considered a pancreatic manifestation of multiorgan disease related to IgG4, and autoimmune pancreatitis type 2 (AIP-2), which is considered a pancreas-specific disease not related to IgG4. Although the pathophysiological conditions seem to differ between type 1 and type 2 pancreatitis, both respond well to steroid medications. In this review, we focused on the pathogenesis of the disease to develop a tool that could facilitate diagnosis and lead to the discovery of new therapeutic strategies to combat autoimmune pancreatitis and its relapses. The standard therapy for AIP is oral administration of corticosteroids. Rituximab (RTX) has also been proposed for induction of remission and maintenance therapy in relapsing AIP-1. In selected patients, immunomodulators such as azathioprine are used to maintain remission. The strength of this review, compared with previous studies, is that it focuses on the clear difference between the two types of autoimmune pancreatitis with a clearly delineated and separate pathogenesis. In addition, the review also considers various therapeutic options, including biologic drugs, such as anti-tumor necrosis factor (TNF) therapy, a well-tolerated and effective second-line therapy for AIP type 2 relapses or steroid dependence. Other biologic therapies are also being explored that could provide a useful therapeutic alternative to corticosteroids and immunosuppressants, which are poorly tolerated due to significant side effects. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases 2.0: Inflammation)
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