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Keywords = molecular gastroenterology

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27 pages, 1326 KiB  
Systematic Review
Application of Artificial Intelligence in Pancreatic Cyst Management: A Systematic Review
by Donghyun Lee, Fadel Jesry, John J. Maliekkal, Lewis Goulder, Benjamin Huntly, Andrew M. Smith and Yazan S. Khaled
Cancers 2025, 17(15), 2558; https://doi.org/10.3390/cancers17152558 - 2 Aug 2025
Viewed by 573
Abstract
Background: Pancreatic cystic lesions (PCLs), including intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), pose a diagnostic challenge due to their variable malignant potential. Current guidelines, such as Fukuoka and American Gastroenterological Association (AGA), have moderate predictive accuracy and may lead [...] Read more.
Background: Pancreatic cystic lesions (PCLs), including intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), pose a diagnostic challenge due to their variable malignant potential. Current guidelines, such as Fukuoka and American Gastroenterological Association (AGA), have moderate predictive accuracy and may lead to overtreatment or missed malignancies. Artificial intelligence (AI), incorporating machine learning (ML) and deep learning (DL), offers the potential to improve risk stratification, diagnosis, and management of PCLs by integrating clinical, radiological, and molecular data. This is the first systematic review to evaluate the application, performance, and clinical utility of AI models in the diagnosis, classification, prognosis, and management of pancreatic cysts. Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD420251008593). Databases searched included PubMed, EMBASE, Scopus, and Cochrane Library up to March 2025. The inclusion criteria encompassed original studies employing AI, ML, or DL in human subjects with pancreatic cysts, evaluating diagnostic, classification, or prognostic outcomes. Data were extracted on the study design, imaging modality, model type, sample size, performance metrics (accuracy, sensitivity, specificity, and area under the curve (AUC)), and validation methods. Study quality and bias were assessed using the PROBAST and adherence to TRIPOD reporting guidelines. Results: From 847 records, 31 studies met the inclusion criteria. Most were retrospective observational (n = 27, 87%) and focused on preoperative diagnostic applications (n = 30, 97%), with only one addressing prognosis. Imaging modalities included Computed Tomography (CT) (48%), endoscopic ultrasound (EUS) (26%), and Magnetic Resonance Imaging (MRI) (9.7%). Neural networks, particularly convolutional neural networks (CNNs), were the most common AI models (n = 16), followed by logistic regression (n = 4) and support vector machines (n = 3). The median reported AUC across studies was 0.912, with 55% of models achieving AUC ≥ 0.80. The models outperformed clinicians or existing guidelines in 11 studies. IPMN stratification and subtype classification were common focuses, with CNN-based EUS models achieving accuracies of up to 99.6%. Only 10 studies (32%) performed external validation. The risk of bias was high in 93.5% of studies, and TRIPOD adherence averaged 48%. Conclusions: AI demonstrates strong potential in improving the diagnosis and risk stratification of pancreatic cysts, with several models outperforming current clinical guidelines and human readers. However, widespread clinical adoption is hindered by high risk of bias, lack of external validation, and limited interpretability of complex models. Future work should prioritise multicentre prospective studies, standardised model reporting, and development of interpretable, externally validated tools to support clinical integration. Full article
(This article belongs to the Section Methods and Technologies Development)
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12 pages, 3342 KiB  
Article
An Additional 30-s Observation of the Right-Sided Colon Using a Novel Endoscopic System with Texture and Color Enhancement Imaging Decreases Polyp Miss Rates: A Multicenter Study
by Yoshikazu Inagaki, Naohisa Yoshida, Hikaru Hashimoto, Yutaka Inada, Takaaki Murakami, Takahito Shimomura, Kyoichi Kassai, Yuri Tomita, Reo Kobayashi, Ken Inoue, Ryohei Hirose, Osamu Dohi and Yoshito Itoh
Diagnostics 2025, 15(14), 1759; https://doi.org/10.3390/diagnostics15141759 - 11 Jul 2025
Viewed by 470
Abstract
Background/Objectives: White light imaging (WLI) of colonoscopy has a 26% adenoma miss rate. We aimed to evaluate the effectiveness of an additional 30 s (Add-30s) observation of the right-sided colon using a novel system (EVIS X1; Olympus Co.) with texture and color enhancement [...] Read more.
Background/Objectives: White light imaging (WLI) of colonoscopy has a 26% adenoma miss rate. We aimed to evaluate the effectiveness of an additional 30 s (Add-30s) observation of the right-sided colon using a novel system (EVIS X1; Olympus Co.) with texture and color enhancement imaging (TXI). Methods: We reviewed 515 patients who underwent colonoscopy with Add-30s TXI between February 2021 and December 2023 at three affiliated hospitals. After initial right-sided colon observation with WLI, the colonoscope was reinserted into the cecum, and the right-sided colon was re-observed with Add-30s TXI. Adenoma and sessile serrated lesion (SSL) detection rate (ASDR) and adenoma detection rate (ADR) were examined. Multivariate analysis identified factors influencing lesion detection using the Add-30s TXI. The difference in WLI and TXI between the novel and previous scopes was performed using propensity score matching (PSM). The efficacy of WLI with the novel system was compared to that of the previous system. Results: Among the 515 cases, Add-30s TXI observation increased right-sided ADR and ASDR by 7.4% and 9.5%, respectively. The multivariate analysis showed novel scope as an independent factor for adenoma and SSL detection (odds ratio: 2.41, p < 0.01). Right-sided ADR and ASDR for Add-30s TXI were significantly higher in the novel scope than the previous scope (ADR, 25.2% vs. 15.3%; p = 0.04; ASDR, 32.4% vs. 18.9%; p = 0.02). ASDR for WLI observation was significantly higher in the novel system than the previous system (34.8% vs. 25.9%; p < 0.01). Conclusions: Add-30s TXI significantly improved the detection of missed adenomas and SSLs in the right-sided colon. Full article
(This article belongs to the Special Issue Recent Advances and Challenges in Gastrointestinal Endoscopy)
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13 pages, 652 KiB  
Review
Evaluating the Risk of Hypophosphatemia with Ferric Carboxymaltose and the Recommended Approaches for Management: A Consensus Statement
by Giuseppe Rosano, Justin Ezekowitz, Elizabeta Nemeth, Piotr Ponikowski, Martina Rauner, Melvin Seid, Donat R. Spahn, Jurgen Stein, Jay Wish and Robert J. Mentz
J. Clin. Med. 2025, 14(14), 4861; https://doi.org/10.3390/jcm14144861 - 9 Jul 2025
Viewed by 1197
Abstract
Background/Objectives: The development of hypophosphatemia has been associated with intravenous iron products, with the rate of hypophosphatemia found to be higher with ferric carboxymaltose. This consensus statement provides clinical guidance on the risk of hypophosphatemia development with ferric carboxymaltose and the approaches for [...] Read more.
Background/Objectives: The development of hypophosphatemia has been associated with intravenous iron products, with the rate of hypophosphatemia found to be higher with ferric carboxymaltose. This consensus statement provides clinical guidance on the risk of hypophosphatemia development with ferric carboxymaltose and the approaches for management. To develop consensus recommendations regarding the clinical implications of hypophosphatemia after the administration of ferric carboxymaltose, the assessment of patient risk profile, and recommended approaches for risk reduction. Methods: Consensus statements were developed from an in-person meeting of specialists with expertise in iron pathophysiology and iron therapy and further supplemented with literature review. The multidisciplinary expert panel comprised global iron specialists spanning anesthesiology, cardiology, gastroenterology, obstetrics/gynecology, hematology, nephrology, and iron molecular biology. Structured discussions were held in an in-person meeting to gather expert opinion on the evidence base regarding intravenous iron and hypophosphatemia. Consolidated summary opinions underwent further iterations of panel review to form consensus recommendation statements. Results: The expert panel developed the following consensus statements: (1) Routine serum phosphate level measurement is not recommended for low-risk patients before or after treatment with ferric carboxymaltose, as most cases of hypophosphatemia that occur following the administration of ferric carboxymaltose are asymptomatic and transient; (2) patients receiving ferric carboxymaltose should be assessed for the degree of risk for developing symptomatic or severe hypophosphatemia prior to administration; (3) monitoring serum phosphate is recommended for patients at an increased risk for developing low serum phosphate or who require repeated courses of ferric carboxymaltose treatment at higher doses; (4) prophylactic oral phosphorus after ferric carboxymaltose is unlikely to effectively elevate phosphate and is not recommended for routine clinical practice; and (5) hypophosphatemic osteomalacia is rare and the risk of development after the administration of ferric carboxymaltose, in particular single infusion, is low. Conclusions: Hypophosphatemia following ferric carboxymaltose is predominantly asymptomatic and transient. Individuals at higher risk for developing hypophosphatemia with ferric carboxymaltose treatment include those who receive multiple infusions, higher cumulative doses, or long-term iron treatment or who have underlying clinical risk factors. These consensus statements provide structured guidance on the risk of hypophosphatemia with ferric carboxymaltose and the approaches to clinical management. Full article
(This article belongs to the Section Hematology)
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13 pages, 537 KiB  
Article
Effects of Blackcurrant Extract and Partially Hydrolyzed Guar Gum Intake on Gut Dysbiosis in Male University Rugby Players
by Hiroto Miura, Machi Oda, Kanako Abe, Hiromi Ikeda, Mami Fujibayashi, Naoko Oda, Tomohiro Segawa, Aya Abe, Natsumi Ueta, Takamitsu Tsukahara, Tomohisa Takagi, Yuji Naito and Ryo Inoue
Microorganisms 2025, 13(7), 1561; https://doi.org/10.3390/microorganisms13071561 - 2 Jul 2025
Viewed by 1482
Abstract
Our previous study reported that male university rugby players tended to have a gut with a dysbiotic environment, characterized by abundant pathobiont bacteria and an accumulation of succinate, when compared with age-matched, non-rugby playing healthy males. In the present study, we conducted a [...] Read more.
Our previous study reported that male university rugby players tended to have a gut with a dysbiotic environment, characterized by abundant pathobiont bacteria and an accumulation of succinate, when compared with age-matched, non-rugby playing healthy males. In the present study, we conducted a randomized, double-blinded, placebo-controlled experiment to evaluate the potential of blackcurrant extract and/or partially hydrolyzed guar gum (PHGG) to improve the gut environment of university rugby players. Participants were supplemented with blackcurrant extract and/or PHGG or a placebo for 4 weeks. Beneficial gut bacteria such as Megasphaera spp. tended to increase (p < 0.10) and Bifidobacterium spp. increased (p < 0.05) with the intake of blackcurrant extract and/or PHGG. A subgroup analysis further indicated that, unlike in those with a eubiotic gut environment, the dietary supplements also increased the number of beneficial gut bacteria such as Phascolarctobacterium spp. (p < 0.10) and Faecalibacterium spp. (p < 0.10) and fecal SCFA concentrations (p < 0.05) in participants with a possible dysbiotic gut environment. However, a synergistic effect between blackcurrant extract and PHGG was not clearly observed. Although further investigation is recommended, it was concluded that blackcurrant extract and PHGG can at least be used as functional materials to improve gut dysbiosis in university rugby players. Full article
(This article belongs to the Special Issue Nutrition and Gut Microbiome)
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14 pages, 7365 KiB  
Article
Improvement of Colonoscopic Image Quality Using a New LED Endoscopic System with Specialized Noise Reduction
by Naohisa Yoshida, Masahiro Okada, Yoshikazu Hayashi, Reo Kobayashi, Ken Inoue, Osamu Dohi, Yoshito Itoh, Ryohei Hirose, Lucas Cardoso, Kohei Suzuki, Tomonori Yano and Hironori Yamamoto
Diagnostics 2025, 15(12), 1569; https://doi.org/10.3390/diagnostics15121569 - 19 Jun 2025
Viewed by 621
Abstract
Background/Objectives: A new LED endoscopy system featuring advanced noise-reduction technology, the EP-8000 with the EC-860ZP colonoscope (Fujifilm), was introduced in 2024. We evaluated the improvements in colonoscopic image quality of this system, comparing it with a previous system/scope (VP-7000/EC-760ZP). Methods: This is a [...] Read more.
Background/Objectives: A new LED endoscopy system featuring advanced noise-reduction technology, the EP-8000 with the EC-860ZP colonoscope (Fujifilm), was introduced in 2024. We evaluated the improvements in colonoscopic image quality of this system, comparing it with a previous system/scope (VP-7000/EC-760ZP). Methods: This is a multicenter, observational study. From January 2024 to February 2025, 150 patients undergoing colonoscopy at two institutions were enrolled. Images of the cecum and lesions were captured using white light imaging (WLI), blue light imaging (BLI), and linked color imaging (LCI) under similar conditions. Participants were divided into three groups: Group 1 (EP-8000+EC-860ZP; 50 cases), Group 2 (EP-8000+EC-760ZP; 50 cases), and Group 3 (VP-7000+EC-760ZP; 50 cases). Cecal and lesion images were evaluated for brightness, halation, and visibility using a four-point scale (1 = poor to 4 = excellent) by endoscopists and original values by image-analysis software. Results: In cecal images, the endoscopists’ scores in Group 1 were significantly better than in Group 3 for brightness (WLI: 3.71 ± 0.55 vs. 3.51 ± 0.58, p < 0.001, BLI: 3.15 ± 0.85 vs. 2.23 ± 0.92, p < 0.001; LCI: 3.83 ± 0.42 vs. 3.54 ± 0.58, p < 0.001) and for halation (WLI: 3.60 ± 0.51 vs. 3.18 ± 0.59, p < 0.001, BLI: 2.99 ± 0.69 vs. 2.71 ± 0.78, p < 0.001; LCI: 3.33 ± 0.60 vs. 3.10 ± 0.58, p < 0.001). Software analysis confirmed that Group 1 had superior brightness values compared with Group 3 for WLI, BLI, and LCI, as well as lower halation values for WLI and LCI. Regarding lesion images, brightness, halation, and visibility for WLI, BLI, and LCI were superior in Group 1 than in Group 3. Conclusions: The new LED system provided improvements in brightness, halation, and lesion visibility. Full article
(This article belongs to the Special Issue New Advances in Digestive Endoscopy)
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17 pages, 1756 KiB  
Review
Ferroptosis in Gastrointestinal Diseases: A New Frontier in Pathogenesis and Therapy
by Adam Wawrzeńczyk, Katarzyna Napiórkowska-Baran, Ewa Alska, Alicja Gruszka-Koselska, Ewa Szynkiewicz, Józef Sławatycki, Paula Klemenska and Zbigniew Bartuzi
J. Clin. Med. 2025, 14(12), 4035; https://doi.org/10.3390/jcm14124035 - 7 Jun 2025
Viewed by 888
Abstract
Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a key player in the pathogenesis of gastrointestinal (GI) diseases. Unlike apoptosis or necrosis, ferroptosis is characterized by distinctive metabolic and molecular pathways, including dysregulated iron metabolism, oxidative [...] Read more.
Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a key player in the pathogenesis of gastrointestinal (GI) diseases. Unlike apoptosis or necrosis, ferroptosis is characterized by distinctive metabolic and molecular pathways, including dysregulated iron metabolism, oxidative stress, and impaired antioxidant defenses. This review explores the complex role of ferroptosis in conditions such as inflammatory bowel disease (IBD), non-alcoholic steatohepatitis (NASH), and gastrointestinal cancers. Special attention is given to the molecular mechanisms underlying ferroptosis, including the Xc/GSH/GPX4 axis, ferritinophagy, ACSL4/LPCAT3-mediated lipid remodeling, and the influence of the gut microbiota. Therapeutic strategies targeting ferroptosis—including pharmacological inhibitors, iron chelators, and microbiota-based interventions—are evaluated for their translational potential, underscoring ferroptosis as a promising target for precision therapies in gastroenterology and highlighting the need for further clinical studies to validate its diagnostic and therapeutic implications. Full article
(This article belongs to the Special Issue Gastrointestinal Diseases: Clinical Challenges and Management)
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20 pages, 2628 KiB  
Review
Confocal Laser Endomicroscopy: Enhancing Intraoperative Decision Making in Neurosurgery
by Francesco Carbone, Nicola Pio Fochi, Giuseppe Di Perna, Arthur Wagner, Jürgen Schlegel, Elena Ranieri, Uwe Spetzger, Daniele Armocida, Fabio Cofano, Diego Garbossa, Augusto Leone and Antonio Colamaria
Diagnostics 2025, 15(4), 499; https://doi.org/10.3390/diagnostics15040499 - 19 Feb 2025
Viewed by 1315
Abstract
Brain tumors, both primary and metastatic, represent a significant global health burden due to their high incidence, mortality, and the severe neurological deficits they frequently cause. Gliomas, especially high-grade gliomas (HGGs), rank among the most aggressive and lethal neoplasms, with only modest gains [...] Read more.
Brain tumors, both primary and metastatic, represent a significant global health burden due to their high incidence, mortality, and the severe neurological deficits they frequently cause. Gliomas, especially high-grade gliomas (HGGs), rank among the most aggressive and lethal neoplasms, with only modest gains in long-term survival despite extensive molecular research and established standard therapies. In neurosurgical practice, maximizing the extent of safe resection is a principal strategy for improving clinical outcomes. Yet, the infiltrative nature of gliomas often complicates the accurate delineation of tumor margins. Confocal laser endomicroscopy (CLE), originally introduced in gastroenterology, has recently gained prominence in neuro-oncology by enabling real-time, high-resolution cellular imaging during surgery. This technique allows for intraoperative tumor characterization and reduces dependence on time-consuming frozen-section analyses. Recent technological advances, including device miniaturization and second-generation CLE systems, have substantially improved image quality and diagnostic utility. Furthermore, integration with deep learning algorithms and telepathology platforms fosters automated image interpretation and remote expert consultations, thereby accelerating surgical decision making and enhancing diagnostic consistency. Future work should address remaining challenges, such as mitigating motion artifacts, refining training protocols, and broadening the range of applicable fluorescent probes, to solidify CLE’s role as a critical intraoperative adjunct in neurosurgical oncology. Full article
(This article belongs to the Special Issue Confocal Microscopy: Clinical Impacts and Innovation, 2nd Edition)
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17 pages, 1519 KiB  
Article
BRAF V600E and Non-V600E Mutations in RAS Wild-Type Metastatic Colorectal Cancer: Prognostic and Therapeutic Insights from a Nationwide, Multicenter, Observational Study (J-BROS)
by Hiroya Taniguchi, Kay Uehara, Toshiaki Ishikawa, Osamu Okochi, Naoya Akazawa, Hiroyuki Okuda, Hiroko Hasegawa, Manabu Shiozawa, Masato Kataoka, Hironaga Satake, Takaya Shimura, Chihiro Kondoh, Hidekazu Kuramochi, Toshihiko Matsumoto, Naoki Takegawa, Toshifumi Yamaguchi, Michitaka Nagase, Masato Nakamura, Nao Takano, Hideto Fujita, Takanori Watanabe, Tomohiro Nishina, Yasuhiro Sakamoto, Toshikazu Moriwaki, Hisatsugu Ohori, Masayoshi Nakanishi, Yosuke Kito, Setsuo Utsunomiya, Takeshi Ishikawa, Dai Manaka, Hiroshi Matsuoka, Takeshi Suto, Toshiyuki Arai, Shinichiro Shinzaki, Tohru Funakoshi, Goro Nakayama, Yuji Negoro, Yasushi Tsuji, Akitaka Makiyama, Kunio Takuma, Atsuki Arimoto, Katsunori Shinozaki, Ayako Mishima and Toshiki Masuishiadd Show full author list remove Hide full author list
Cancers 2025, 17(3), 399; https://doi.org/10.3390/cancers17030399 - 25 Jan 2025
Cited by 1 | Viewed by 2041
Abstract
Background/Objectives: BRAF mutations occur in 5–10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. Methods: This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. Results: [...] Read more.
Background/Objectives: BRAF mutations occur in 5–10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. Methods: This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. Results: BRAF mutations were identified in 21% (79/377) of cases, predominantly V600E (89.9%) with a minority of non-V600E (10.1%). Microsatellite instability (MSI) testing revealed MSI-high in 11.3%, exclusively among V600E cases. V600E mutations were linked to right-sided tumors, poor differentiation, and elevated CA19-9 levels. Median survival was significantly lower in V600E cases compared to BRAF wild-type (12.4 vs. 37.5 months, HR 3.25, p < 0.001) and marginally lower non-V600E cases (12.4 vs. 34.7 months, HR 0.61, p = 0.057). Chemotherapy regimens (doublet vs. triplet) and targeted treatments (bevacizumab vs. anti-EGFR) showed no significant survival differences in V600E patients. Similarly, RAS/BRAF wild-type patients had comparable survival with bevacizumab versus anti-EGFR, even for left-sided tumors. Conclusions: These findings highlight distinct clinical and prognostic profiles for BRAF V600E and non-V600E mutations, while treatment choice appears to have limited impact on survival in these subgroups or RAS/BRAF wild-type cases. Full article
(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)
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15 pages, 4795 KiB  
Article
Epithelial–Mesenchymal Transition Suppression by ML210 Enhances Gemcitabine Anti-Tumor Effects on PDAC Cells
by Keisuke Takemura, Kyohei Ikeda, Hayato Miyake, Yoshio Sogame, Hiroaki Yasuda, Nobuhiro Okada, Kazumi Iwata, Junichi Sakagami, Kanji Yamaguchi, Yoshito Itoh and Atsushi Umemura
Biomolecules 2025, 15(1), 70; https://doi.org/10.3390/biom15010070 - 6 Jan 2025
Cited by 2 | Viewed by 1309
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the world. Neoadjuvant chemotherapy (NAC) has become a standard treatment for patients scheduled for surgical resection, but the high rate of postoperative recurrence is a critical problem. Optimization of NAC is desirable [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the world. Neoadjuvant chemotherapy (NAC) has become a standard treatment for patients scheduled for surgical resection, but the high rate of postoperative recurrence is a critical problem. Optimization of NAC is desirable to reduce postoperative recurrence and achieve long-term survival. However, if a patient’s general condition deteriorates due to NAC toxicity, surgical outcomes may be compromised. Therefore, we aimed to identify drug(s) that can be used in combination with gemcitabine (GEM), a drug widely used for the treatment of PDAC, to inhibit distant metastatic recurrence, particularly after surgery. After several screening steps, ML210, a low molecular weight chemical, was found to suppress the epithelial–mesenchymal transition (EMT) in PDAC cells in combination with GEM. Specifically, low dose ML210 in combination with GEM was sufficient for cell migration without apparent toxicity or cell death. Mechanistically, ML210, which was developed as a glutathione peroxidase 4 (GPX4) inhibitor to induce lipid peroxidation, increased the oxidized lipid concentrations in PDAC cells. The oxidization of the cell membrane lipids may suppress EMT, including cell migration. Since EMT is a major malignant phenotype of PDAC, our findings may lead to the advancement of PDAC therapy, especially in the prevention of postoperative recurrence. Full article
(This article belongs to the Section Cellular Biochemistry)
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26 pages, 7731 KiB  
Review
Key Interleukins in Inflammatory Bowel Disease—A Review of Recent Studies
by David Aebisher, Dorota Bartusik-Aebisher, Agnieszka Przygórzewska, Piotr Oleś, Paweł Woźnicki and Aleksandra Kawczyk-Krupka
Int. J. Mol. Sci. 2025, 26(1), 121; https://doi.org/10.3390/ijms26010121 - 26 Dec 2024
Cited by 8 | Viewed by 5476
Abstract
Inflammatory bowel disease (IBD) is an immune disorder of the gastrointestinal tract with a complex aetiopathogenesis, whose development is influenced by many factors. The prevalence of IBD is increasing worldwide, in both industrialized and developing countries, making IBD a global health problem that [...] Read more.
Inflammatory bowel disease (IBD) is an immune disorder of the gastrointestinal tract with a complex aetiopathogenesis, whose development is influenced by many factors. The prevalence of IBD is increasing worldwide, in both industrialized and developing countries, making IBD a global health problem that seriously affects quality of life. In 2019, there were approximately 4.9 million cases of IBD worldwide. Such a large number of patients entails significant healthcare costs. In the treatment of patients with IBD, the current therapeutic target is mucosal healing, as intestinal inflammation often persists despite resolution of abdominal symptoms. Treatment strategies include amino salicylates, corticosteroids, immunosuppressants, and biologic therapies that focus on reducing intestinal mucosal inflammation, inducing and prolonging disease remission, and treating complications. The American College of Gastroenterology (ACG) guidelines also indicate that nutritional therapies may be considered in addition to other therapies. However, current therapeutic approaches are not fully effective and are associated with various limitations, such as drug resistance, variable efficacy, and side effects. As the chronic inflammation that accompanies IBD is characterized by infiltration of a variety of immune cells and increased expression of a number of pro-inflammatory cytokines, including IL-6, TNF-α, IL-12, IL-23 and IFN-γ, new therapeutic approaches are mainly targeting immune pathways. Interleukins are one of the molecular targets in IBD therapy. Interleukins and related cytokines serve as a means of communication for innate and adaptive immune cells, as well as nonimmune cells and tissues. These cytokines play an important role in the pathogenesis and course of IBD, making them promising targets for current and future therapies. In our work, we review scientific studies published between January 2022 and November 2024 describing the most important interleukins involved in the pathogenesis of IBD. Some of the papers present new data on the precise role that individual interleukins play in IBD. New clinical data have also been provided, particularly on blocking interleukin 23 and interleukin 1beta. In addition, several new approaches to the use of different interleukins in the treatment of IBD have been described in recent years. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Advances in Biochemistry)
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31 pages, 1612 KiB  
Review
TSAT-Urated Insights: Clarifying the Complexities of Hereditary Hemochromatosis and Its Guidelines
by Chiara Marcon, Marta Medeot, Alessio Michelazzi, Valentina Simeon, Alessandra Poz, Sara Cmet, Elisabetta Fontanini, Anna Rosa Cussigh, Marianna Chiozzotto and Giovanni Barillari
Hemato 2024, 5(4), 459-489; https://doi.org/10.3390/hemato5040035 - 11 Dec 2024
Viewed by 4540
Abstract
Hereditary hemochromatosis (HH) related to HFE-gene mutations is a well-known condition, yet its understanding remains complex. The BIOIRON classification emphasizes that only homozygosity for the C282Y mutation should be considered pathogenic. The penetrance of HFE-related HH is highly variable. Symptoms are often challenging [...] Read more.
Hereditary hemochromatosis (HH) related to HFE-gene mutations is a well-known condition, yet its understanding remains complex. The BIOIRON classification emphasizes that only homozygosity for the C282Y mutation should be considered pathogenic. The penetrance of HFE-related HH is highly variable. Symptoms are often challenging to recognize at the time of presentation, and the systemic involvement may overlap with other diseases. Hyperferritinemia and elevated transferrin saturation levels are still the milestones in HH diagnosis, but they are also common findings in many other clinical conditions. Furthermore, current diagnostic and therapeutic guidelines are not always unequivocal in defining HH patients’ characteristics, as well as treatment management and goals. Our work provides a concise overview of the latest evidence regarding pathogenic mechanisms, clinical picture, differential diagnosis and diagnostic tools. Alongside this, it summarizes and compares the main recommendations from principal guidelines issued by the 2017 Hemochromatosis International Meeting, the American College of Gastroenterology, the European Association for the Study of the Liver, the European Molecular Genetics Quality Network, the DUTCH guidelines, and the British Society for Haematology. Summarizing tables for quick consultation are also provided. Full article
(This article belongs to the Section Non Neoplastic Blood Disorders)
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18 pages, 3557 KiB  
Article
A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor Pathway
by Panagiotis Ntavaroukas, Konstantinos Michail, Rafaela Tsiakalidou, Eleni Stampouloglou, Aikaterini Tsingene, Dimitrios Komiotis, Nikitas Georgiou, Thomas Mavromoustakos, Stella Manta, Danielle Aje, Panagiotis Michael, Barry J. Campbell and Stamatia Papoutsopoulou
Biology 2024, 13(11), 910; https://doi.org/10.3390/biology13110910 - 7 Nov 2024
Cited by 1 | Viewed by 1910
Abstract
The NF-κB family of transcription factors is a master regulator of cellular responses during inflammation, and its dysregulation has been linked to chronic inflammatory diseases, such as inflammatory bowel disease. It is therefore of vital importance to design and test new effective NF-κB [...] Read more.
The NF-κB family of transcription factors is a master regulator of cellular responses during inflammation, and its dysregulation has been linked to chronic inflammatory diseases, such as inflammatory bowel disease. It is therefore of vital importance to design and test new effective NF-κB inhibitors that have the potential to be utilized in clinical practice. In this study, we used a commercial transgenic HeLa cell line as an NF-κB activation reporter to test a novel quinoline molecule, Q3, as a potential inhibitor of the canonical NF-κB pathway. Q3 inhibited NF-κB-induced luciferase in concentrations as low as 5 μM and did not interfere with cell survival or induced cell death. A real-time PCR analysis revealed that Q3 could inhibit the TNF-induced transcription of the luciferase gene, as well as the TNF gene, a known downstream target gene. Immunocytochemistry studies revealed that Q3 moderately interferes with TNF-induced NF-κB nuclear translocation. Moreover, docking and molecular dynamics analyses confirmed that Q3 could potentially modulate transcriptional activity by inhibiting the interaction of NF-κB and DNA. Therefore, Q3 could be potentially developed for further in vivo studies as an NF-κB inhibitor. Full article
(This article belongs to the Special Issue NF-κB and Its Role in Health and Disease)
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12 pages, 454 KiB  
Article
Association of Serum Bile Acid Profile with Diet and Physical Activity Habits in Japanese Middle-Aged Men
by Wataru Aoi, Teruhide Koyama, Akira Honda, Tomohisa Takagi and Yuji Naito
Nutrients 2024, 16(19), 3381; https://doi.org/10.3390/nu16193381 - 4 Oct 2024
Cited by 2 | Viewed by 1697
Abstract
Background/Objectives: Circulating bile acid (BA) profiles change with lifestyle and are closely related to intestinal BA metabolisms such as deconjugation and conversion to secondary BAs. The composition of BA in the blood is involved in systemic nutrient metabolism and intestinal health. Herein, we [...] Read more.
Background/Objectives: Circulating bile acid (BA) profiles change with lifestyle and are closely related to intestinal BA metabolisms such as deconjugation and conversion to secondary BAs. The composition of BA in the blood is involved in systemic nutrient metabolism and intestinal health. Herein, we explored the associations of lifestyle and physical fitness with the circulating BA profile of middle-aged men. Methods: Data of 147 male participants (aged 50–64 years; BMI < 26 kg/m2; no medication for diabetes or dyslipidemia) from the Japan Multi-Institutional Collaborative Cohort study were analyzed. Serum concentrations of 15 types of BAs were examined for associations with variables on dietary habits, physical-activity habits, and physical fitness. Results: Green tea intake was positively associated with the deconjugation ratio of total BAs (p = 0.028) and negatively associated with secondary BA levels (free deoxycholic acid [DCA] (p = 0.078), glyco-DCA (p = 0.048), and tauro-DCA (p = 0.037)). In contrast, physical activity was negatively associated with the deconjugation ratio (p = 0.029) and secondary BA levels (free DCA (p = 0.098), and free lithocholic acid (p = 0.009)). Grip strength was also negatively associated with secondary BA levels (tauro-DCA (p = 0.041)) but was not associated with the deconjugation ratio. Energy and fat intake and skeletal muscle mass were not associated with the deconjugation ratio or secondary BA levels. Conclusions: The study findings suggest that lifestyle-associated changes in serum deconjugated and secondary BAs indicate improvements in nutrient metabolism and the intestinal environment. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health — 2nd Edition)
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13 pages, 1439 KiB  
Article
Shotgun Analysis of Gut Microbiota with Body Composition and Lipid Characteristics in Crohn’s Disease
by Péter Bacsur, Tamás Resál, Bernadett Farkas, Boldizsár Jójárt, Zoltán Gyuris, Gábor Jaksa, Lajos Pintér, Bertalan Takács, Sára Pál, Attila Gácser, Kata Judit Szántó, Mariann Rutka, Renáta Bor, Anna Fábián, Klaudia Farkas, József Maléth, Zoltán Szepes, Tamás Molnár and Anita Bálint
Biomedicines 2024, 12(9), 2100; https://doi.org/10.3390/biomedicines12092100 - 14 Sep 2024
Cited by 1 | Viewed by 1355
Abstract
Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn’s disease (CD). In our cross-sectional study, patients [...] Read more.
Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn’s disease (CD). In our cross-sectional study, patients with CD were enrolled and blood and fecal samples were collected. Clinical and endoscopic disease activity and body composition were assessed and laboratory tests were made. Fecal bacterial composition was analyzed using the shotgun method. Microbiota alterations based on obesity, lipid parameters, and disease characteristics were analyzed. In this study, 27 patients with CD were analyzed, of which 37.0% were obese based on visceral fat area (VFA). Beta diversities were higher in non-obese patients (p < 0.001), but relative abundances did not differ. C. innocuum had a higher abundance at a high cholesterol level than Bacillota (p = 0.001, p = 0.0034). Adlercreutzia, B. longum, and Blautia alterations were correlated with triglyceride levels. Higher Clostridia (p = 0.009) and B. schinkii (p = 0.032) and lower Lactobacillus (p = 0.035) were connected to high VFA. Disease activity was coupled with dysbiotic elements. Microbiota alterations in obesity highlight the importance of gut microbiota in diseases with a similar inflammatory background and project therapeutic options. Full article
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21 pages, 338 KiB  
Review
Evolution of Systemic Treatment for Hepatocellular Carcinoma: Changing Treatment Strategies and Concepts
by Michihisa Moriguchi, Seita Kataoka and Yoshito Itoh
Cancers 2024, 16(13), 2387; https://doi.org/10.3390/cancers16132387 - 28 Jun 2024
Cited by 6 | Viewed by 3603
Abstract
Systemic therapy for hepatocellular carcinoma (HCC) has undergone substantial advancements. With the advent of atezolizumab plus bevacizumab (ATZ/BEV) combination therapy, followed by durvalumab plus tremelimumab, the era of immunotherapy for HCC has commenced. The emergence of systemic treatment with high response rates has [...] Read more.
Systemic therapy for hepatocellular carcinoma (HCC) has undergone substantial advancements. With the advent of atezolizumab plus bevacizumab (ATZ/BEV) combination therapy, followed by durvalumab plus tremelimumab, the era of immunotherapy for HCC has commenced. The emergence of systemic treatment with high response rates has led to improvements in overall survival while enabling conversion to radical surgical resection in some patients with HCC. In patients with intermediate-stage HCC, new treatment strategies combining systemic treatment and transcatheter arterial chemoembolization (TACE) are under development in clinical trials. Moreover, the addition of local therapies, such as TACE, to systemic treatment according to the treatment effect could achieve a certain percentage of complete response. In the IMbrave050 trial, the efficacy of ATZ/BEV combination therapy was validated in patients predicted to have a high risk of recurrence, especially in those who had undergone radical surgery or radiofrequency ablation for HCC. Therefore, systemic treatment for HCC is entering a new phase for all disease stages. The objective of this review is to organize the current position of systemic therapy for each HCC stage and discuss the development of new treatment methods and strategies, with a focus on regimens incorporating immune checkpoint inhibitors, along with future prospects. Full article
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