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Metabolic Basis of Inflammation and Carcinogenesis in Digestive Disorders
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Metabolic Basis of Inflammation and Carcinogenesis in Digestive Disorders

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

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 12551

Special Issue Editors

Dr. Yoshinori Harada

E-Mail Website
Guest Editor
Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
Interests: pathology; metabolism; hepatology; gastroenterology; cardiology; bioimaging; Raman spectroscopy
Dr. Yasuko Fujita

E-Mail Website
Guest Editor
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Aichi 464-8681, Japan
Interests: pathology; gastroenterology; cancer; gastrointestinal neoplasm; molecular oncology
Dr. Hiroaki Yasuda

E-Mail Website
Guest Editor
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kajii-cho 465, Kamigyo-ku, Kyoto 602-8566, Japan
Interests: gastroenterology; pancreatology; endoscopic ultrasonography; oncology; bile duct

Special Issue Information

Dear Colleagues,

The concept of metabolic dysfunction-associated fatty liver disease (MAFLD), which is related to various metabolic disorders including diabetes, has been proposed, and the scope of research on fatty liver diseases is expanding. Moreover, it has been reported that metabolic abnormalities such as diabetes and dyslipidemia may affect onset and progression of digestive organ cancers. Metabolic basis of inflammation and carcinogenesis in digestive disorders that have recently attracted attention include nonalcoholic steatohepatitis, pancreatic tumor, and colon cancer. This special topic is prompting original articles and reviews that address metabolic basis of inflammation and carcinogenesis in digestive disorders including MAFLD. Manuscripts on metabolic imaging of cancers including other organs are also welcomed. We hope that this topic will be helpful for the readers of IJMS in furthering the growing understanding and the latest knowledge of basic research and clinical research from various angles for future research and medical care.

Suggested Topics:

  1. Lipid metabolism and inflammation in MAFLD;
  2. Mechanisms of insulin resistance and hepatic steatosis/fibrosis;
  3. Mechanisms of neoplasm development in MAFLD;
  4. Bioimage analysis of MAFLD/cancers;
  5. Metabolic transformation during carcinogenesis;
  6. Roles of lipid droplets in cancers;
  7. Lipid metabolism in cancers;
  8. The Warburg effect in cancer/non-cancer cells.

Dr. Yoshinori Harada
Dr. Yasuko Fujita
Dr. Hiroaki Yasuda
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

  • metabolic dysfunction-associated fatty liver disease
  • nonalcoholic fatty liver disease
  • nonalcoholic steatohepatitis
  • carcinoma
  • lipid metabolism
  • Warburg effect

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Published Papers (3 papers)

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Research

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17 pages, 4403 KiB  
Article
Assessment of Ultra-Early-Stage Liver Fibrosis in Human Non-Alcoholic Fatty Liver Disease by Second-Harmonic Generation Microscopy
by Takeo Minamikawa, Eiji Hase, Mayuko Ichimura-Shimizu, Yuki Morimoto, Akihiro Suzuki, Takeshi Yasui, Satoko Nakamura, Akemi Tsutsui, Koichi Takaguchi and Koichi Tsuneyama
Int. J. Mol. Sci. 2022, 23(6), 3357; https://doi.org/10.3390/ijms23063357 - 20 Mar 2022
Cited by 4 | Viewed by 3492
Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with the chronic progression of fibrosis. In general, the progression of liver fibrosis is determined by a histopathological assessment with a collagen-stained section; however, the ultra-early stage of liver fibrosis is challenging to identify because of [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is associated with the chronic progression of fibrosis. In general, the progression of liver fibrosis is determined by a histopathological assessment with a collagen-stained section; however, the ultra-early stage of liver fibrosis is challenging to identify because of the low sensitivity in the collagen-selective staining method. In the present study, we demonstrate the feasibility of second-harmonic generation (SHG) microscopy in the histopathological diagnosis of the liver of NAFLD patients for the quantitative assessment of the ultra-early stage of fibrosis. We investigated four representative NAFLD patients with early stages of fibrosis. SHG microscopy visualised well-matured fibrotic structures and early fibrosis diffusely involving liver tissues, whereas early fibrosis is challenging to be identified by conventional histopathological methods. Furthermore, the SHG emission directionality analysis revealed the maturation of each collagen fibre of each patient. As a result, SHG microscopy is feasible for assessing liver fibrosis on NAFLD patients, including the ultra-early stage of liver fibrosis that is difficult to diagnose by the conventional histopathological method. The assessment method of the ultra-early fibrosis by using SHG microscopy may serve as a crucial means for pathological, clinical, and prognostic diagnosis of NAFLD patients. Full article
(This article belongs to the Special Issue Metabolic Basis of Inflammation and Carcinogenesis in Digestive Disorders)
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12 pages, 1798 KiB  
Article
Accumulation of Uroporphyrin I in Necrotic Tissues of Squamous Cell Carcinoma after Administration of 5-Aminolevulinic Acid
by Masatomo Beika, Yoshinori Harada, Takeo Minamikawa, Yoshihisa Yamaoka, Noriaki Koizumi, Yasutoshi Murayama, Hirotaka Konishi, Atsushi Shiozaki, Hitoshi Fujiwara, Eigo Otsuji, Tetsuro Takamatsu and Hideo Tanaka
Int. J. Mol. Sci. 2021, 22(18), 10121; https://doi.org/10.3390/ijms221810121 - 19 Sep 2021
Cited by 7 | Viewed by 3343
Abstract
5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is widely used for the intraoperative detection of malignant tumors. However, the fluorescence emission profiles of the accompanying necrotic regions of these tumors have yet to be determined. To address this, we performed fluorescence and high-performance [...] Read more.
5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is widely used for the intraoperative detection of malignant tumors. However, the fluorescence emission profiles of the accompanying necrotic regions of these tumors have yet to be determined. To address this, we performed fluorescence and high-performance liquid chromatography (HPLC) analyses of necrotic tissues of squamous cancer after 5-ALA administration. In resected human lymph nodes of metastatic squamous cell carcinoma, we found a fluorescence peak at approximately 620 nm in necrotic lesions, which was distinct from the PpIX fluorescence peak at 635 nm for viable cancer lesions. Necrotic lesions obtained from a subcutaneous xenograft model of human B88 oral squamous cancer also emitted the characteristic fluorescence peak at 620 nm after light irradiation: the fluorescence intensity ratio (620 nm/635 nm) increased with the energy of the irradiation light. HPLC analysis revealed a high content ratio of uroporphyrin I (UPI)/total porphyrins in the necrotic cores of murine tumors, indicating that UPI is responsible for the 620 nm peak. UPI accumulation in necrotic tissues after 5-ALA administration was possibly due to the failure of the heme biosynthetic pathway. Taken together, fluorescence imaging of UPI after 5-ALA administration may be applicable for the evaluation of tumor necrosis. Full article
(This article belongs to the Special Issue Metabolic Basis of Inflammation and Carcinogenesis in Digestive Disorders)
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Review

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23 pages, 3404 KiB  
Review
5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges
by Yoshinori Harada, Yasutoshi Murayama, Tetsuro Takamatsu, Eigo Otsuji and Hideo Tanaka
Int. J. Mol. Sci. 2022, 23(12), 6478; https://doi.org/10.3390/ijms23126478 - 9 Jun 2022
Cited by 51 | Viewed by 4767
Abstract
5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of heme and chlorophyll. Exogenously administered 5-ALA is metabolized into protoporphyrin IX (PpIX). PpIX accumulates in cancer cells because of the low activity of ferrochelatase, an enzyme that metabolizes PpIX to heme. [...] Read more.
5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of heme and chlorophyll. Exogenously administered 5-ALA is metabolized into protoporphyrin IX (PpIX). PpIX accumulates in cancer cells because of the low activity of ferrochelatase, an enzyme that metabolizes PpIX to heme. High expression of 5-ALA influx transporters, such as peptide transporters 1/2, in cancer cells also enhances PpIX production. Because PpIX radiates red fluorescence when excited with blue/violet light, 5-ALA has been used for the visualization of various tumors. 5-ALA photodynamic diagnosis (PDD) has been shown to improve the tumor removal rate in high-grade gliomas and non-muscular invasive bladder cancers. However, 5-ALA PDD remains a challenge as a diagnostic method because tissue autofluorescence interferes with PpIX signals in cases where tumors emit only weak signals, and non-tumorous lesions, such as inflammatory sites, tend to emit PpIX fluorescence. Here, we review the current outline of 5-ALA PDD and strategies for improving its diagnostic applicability for tumor detection, focusing on optical techniques and 5-ALA metabolic pathways in both viable and necrotic tumor tissues. Full article
(This article belongs to the Special Issue Metabolic Basis of Inflammation and Carcinogenesis in Digestive Disorders)
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