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Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 August 2025) | Viewed by 16342

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Dr. Felipe Leite De Oliveira

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Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
Interests: gastroenterology; gastrointestinal diseases; cancer; mucosal inflammation
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Special Issue Information

Dear Colleagues,

Diseases of the gastrointestinal tract encompass a wide range of disorders that affect the digestive system, and they have attracted the attention of researchers and health professionals around the world. The cellular and molecular mechanisms underlying these diseases, such as inflammatory bowel diseases, irritable bowel syndrome, gastroesophageal reflux, peptic ulcer, celiac disease, gastrointestinal motility disorders, liver diseases, and others, are diverse and involve various components of the gastrointestinal tract. Papers addressing gastrointestinal comorbidities are also welcome in this Special Issue. Cell targets are present in the epithelial barriers, mucosal tissues, accessory glands, immune system, enteric nervous system, neuromuscular junctions, and others. Molecular signaling includes mechanisms that regulate inflammation (cytokines and chemokines), fibrosis, aberrant immune responses, genetic susceptibility, abnormalities in the gut–brain axis, visceral hypersensitivity, pathogens, disruption of mucosa, cancer, smooth muscle abnormalities, and others. Understanding these cellular and molecular mechanisms is crucial for developing targeted therapies, diagnostic tools, and interventions for the diverse array of gastrointestinal diseases resulting in precision medicine and personalized treatment approaches. Studies in this area involve the oral cavity, esophagus, stomach, small and large intestines, salivary glands, liver, pancreas, and gallbladder. This Special Issue aims to improve both preventive and therapeutic protocols and methodologies for precision diagnosis. Advances in molecular and cell biology in gastrointestinal diseases continue to enhance our understanding of these mechanisms and drive innovation in medical research and healthcare. Papers on other topics linked to gastrointestinal tract diseases not included here, however, will also be considered by the editorial team.

Dr. Felipe Leite De Oliveira
Guest Editor

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Keywords

cellular mechanisms
molecular mechanisms
diagnosis
treatment
experimental models
signaling pathways
comorbidities

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Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease: 2nd Edition in Biomedicines

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12 pages, 1306 KB

Open AccessArticle

Interferon Regulator Factor 5: A Novel Inflammatory Marker and Promising Therapeutic Target in Ulcerative Colitis

by Karima Farrag, Aysegül Aksan, Marina Korotkova, Helena Idborg, Per-Johan Jakobsson, Andreas Weigert, Michael Vieth, Stefan Zeuzem, Irina Blumenstein and Jürgen Stein

Biomedicines 2025, 13(9), 2251; https://doi.org/10.3390/biomedicines13092251 - 12 Sep 2025

Viewed by 315

Abstract

Background: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation affecting the gastrointestinal tract and extraintestinal organs. The etiology of IBD is multifactorial, involving genetic, immunological, and environmental factors. Over 200 genetic loci have been associated with the disease, indicating a significant genetic predisposition. Despite advances in understanding its genetic basis, clinical management remains challenging due to heterogeneity in disease presentation and variable treatment responses. Current therapies, such as 5-aminosalicylates and biologics, are not universally effective, underscoring the need for reliable biomarkers to predict therapeutic responses. Objective: This study investigates the potential role of interferon regulatory factor 5 (IRF5) in the pathogenesis of IBD, with a particular focus on UC. Methods: We conducted a systematic analysis of colon biopsies from 30 adult patients diagnosed with UC and from 8 non-IBD controls. Immunostaining was performed to assess IRF5 expression in colonic tissues using the primary IRF5 antibody (1:300, Abcam, ab181553). Statistical analyses evaluated the correlation between IRF5-positive cell counts, disease activity, and inflammatory markers such as calprotectin. Results: Our analysis revealed a significant increase in IRF5-positive macrophage-like cells in the inflamed mucosa of IBD patients compared to healthy controls. The number of IRF5-positive cells showed a positive correlation with disease activity and calprotectin levels, indicating that higher IRF5 expression is associated with increased inflammation. Conclusions: This study demonstrates a significant correlation between IRF5 expression and disease activity in UC, suggesting that IRF5 may play a crucial role in the inflammatory processes of the disease. The findings propose IRF5 as a novel biomarker for therapeutic intervention in IBD. Further research is needed to clarify the mechanisms by which IRF5 contributes to IBD pathogenesis and to explore the therapeutic potential of targeting this pathway in clinical settings. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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22 pages, 2987 KB

Open AccessArticle

Proteomic Profiling of EUS-FNA Samples Differentiates Pancreatic Adenocarcinoma from Mass-Forming Chronic Pancreatitis

by Casandra Teodorescu, Ioana-Ecaterina Pralea, Maria-Andreea Soporan, Rares Ilie Orzan, Maria Iacobescu, Andrada Seicean and Cristina-Adela Iuga

Biomedicines 2025, 13(9), 2199; https://doi.org/10.3390/biomedicines13092199 - 8 Sep 2025

Viewed by 361

Abstract

Background/Objectives: Mass-forming chronic pancreatitis (MFP) and pancreatic ductal adenocarcinoma (PDAC) can present with overlapping radiological, clinical, and serological features in patients with underlying chronic pancreatitis (CP), making differential diagnosis particularly challenging. Current diagnostic tools, including CA19-9 and endoscopic ultrasound (EUS) imaging, often lack the specificity needed to reliably distinguish between these conditions. The objective of this study was to investigate whether the proteomic profiling of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples could provide molecular-level discrimination between MFP and PDAC in patients with CP. Methods: Thirty CP patients with solid pancreatic lesions were prospectively enrolled: 15 with histologically confirmed PDAC and 15 with MFP. Traditional diagnostic parameters, including CA19-9 levels and EUS characteristics, were recorded but found insufficient for differentiation. EUS-FNA samples were analyzed using label-free mass spectrometry. A total of 928 proteins were identified in PDAC samples and 555 in MFP samples. Differential abundance analysis and pathway enrichment were performed. Results: Overall, 88 proteins showed significant differential abundance between PDAC and MFP samples, of which 26 met stringent statistical thresholds. Among these, Carboxylesterase 2 (CES2), Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1), Lumican (LUM), Transmembrane Protein 205 (TMEM205), and NAD(P)H Quinone Dehydrogenase 1 (NQO1) emerged as key discriminatory proteins. Pathway enrichment analysis revealed distinct biological processes between the groups, including mitochondrial fatty acid β-oxidation, Rho GTPase signaling, and platelet degranulation. Conclusions: Proteomic signatures derived from EUS-FNA samples offer a promising molecular approach to distinguish inflammatory pseudotumoral lesions from malignant pancreatic tumors in CP patients. This minimally invasive strategy could enhance diagnostic accuracy where current methods fall short. Further validation in larger, multicenter cohorts is warranted to confirm these findings and evaluate their clinical applicability. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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15 pages, 2455 KB

Open AccessArticle

Mechanistic Insights into a Self-Management Intervention in Young Adults with Irritable Bowel Syndrome: A Pilot Multi-Omics Study

by Weizi Wu, Jie Chen, Aolan Li, Ming-Hui Chen, Angela Starkweather and Xiaomei Cong

Biomedicines 2025, 13(9), 2102; https://doi.org/10.3390/biomedicines13092102 - 28 Aug 2025

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Abstract

Background: Self-directed lifestyle modifications are essential for managing symptoms in individuals diagnosed with irritable bowel syndrome (IBS). This study incorporated longitudinal multi-omics profiling to estimate the mechanisms underlying responses to a nurse-led person-centered self-management intervention in young adults with IBS. Methods: This pre-post study was nested within a 12-week parent randomized controlled trial (NCT03332537). Biospecimens (stool and blood) and clinical outcomes were collected at baseline and post-intervention. Symptoms were assessed using the Brief Pain Inventory and PROMIS^® short forms. Host transcriptomic profiling was performed using RNA sequencing, and gut microbial composition was analyzed via 16S rRNA sequencing. Host transcriptomic co-expression and microbial co-abundance modules were identified via weighted gene co-expression network analysis. Associations between multi-omics modules and symptoms were evaluated using linear mixed-effect models. Results: Among the 20 participants, most were non-Hispanic (75%), White (75%), and female (65%). The intervention significantly reduced self-reported pain severity (p = 0.019) and pain interference (p = 0.013). Decreased associations were observed between pain phenotypes and a microbial module enriched in core metabolic pathways (interference: β = −4.7, p < 0.001; severity: β = −2.4, p = 0.02). Anxiety strengthened associations with host transcriptomic cellular energy metabolism pathways post-intervention (p < 0.05). The intervention attenuated associations between fatigue, sleep disturbance, and immune–inflammatory transcriptomic and microbial adaptation modules (p < 0.05). Conclusions: Findings suggest that the IBS self-management intervention induces symptom-specific biological responses, implicating distinct host–microbe pathways. Larger longitudinal studies are warranted to validate these omics-based symptom signatures. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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13 pages, 580 KB

Open AccessArticle

Molecular Detection and Clinical Impact of Helicobacter pylori Virulence Genes in Gastric Diseases: A Study in Arequipa, Peru

by Yuma Ita-Balta, Alice Zegarra-Adanaque, Johany Sanchez-Guillen, Miguel Farfán-Delgado, Carlos Ortiz-Castro, Alexis Germán Murillo Carrasco, Alejandro Miranda Pinto and Cecilia Manrique-Sam

Biomedicines 2025, 13(4), 914; https://doi.org/10.3390/biomedicines13040914 - 9 Apr 2025

Cited by 1 | Viewed by 1731

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Background: Helicobacter pylori is a globally prevalent pathogen and a major contributor to gastric diseases, including chronic gastritis, peptic ulcer disease, and gastric cancer. This study investigates the prevalence, distribution, and clinical relevance of its key virulence genes, vacA and cagA, in a Peruvian patient cohort. Materials and Methods: Fifty-one gastric biopsies were collected from patients with a presumptive diagnosis of H. pylori-induced gastritis at Hospital Carlos Alberto Seguín Escobedo in Arequipa, Peru, in March 2024. Two biopsies per patient—one from the antrum and one from the gastric body—were obtained during endoscopy. DNA extraction was performed using the Quick-DNA Fungal/Bacterial Kit (Zymo Research, USA). Molecular identification of H. pylori was conducted via PCR targeting the glmM gene, while the vacA and cagA virulence genes were detected using specific primers. Statistical analyses, including Pearson’s chi-square and Mann–Whitney tests, were applied to assess associations between virulence gene presence and clinical or histopathological variables. Results: Among the gastric biopsies, the vacA gene was detected in 37.3% of samples, while cagA was present in 17.6%. Statistical analysis revealed significant associations between vacA and specific clinical and endoscopic features, including erythematous gastropathy, nodular gastritis, and emetic syndrome, suggesting its localized role in disease pathogenesis. Additionally, the presence of cagA was significantly linked to moderate inflammatory intensity in gastric body biopsies, indicating its association with more severe histopathological outcomes. Chronic gastritis was the most common histopathological finding, with moderate intensity correlating strongly with the presence of virulence genes. Conclusions: These findings highlight substantial regional variability in the distribution and pathogenicity of H. pylori genotypes. This study underscores the importance of incorporating molecular diagnostics into routine clinical practice to improve diagnostic accuracy and inform region-specific therapeutic strategies. This is particularly crucial in endemic regions like Peru, where unique environmental and genetic factors may influence infection dynamics and disease outcomes. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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20 pages, 5920 KB

Open AccessArticle

UHT Cow’s Milk Supplementation Affects Cell Niches and Functions of the Gut–Brain Axis in BALB/c Mice

by Felipe S. Lemos, Caio A. Prins, Ana M. B. Martinez, Raul Carpi-Santos, Arthur S. Neumann, Nathalia Meireles-da-Costa, Roberto Luisetto, Valeria de Mello-Coelho and Felipe L. Oliveira

Biomedicines 2024, 12(11), 2448; https://doi.org/10.3390/biomedicines12112448 - 25 Oct 2024

Cited by 1 | Viewed by 1944

Abstract

Background/Objectives: Cow’s milk is a bioactive cocktail with essential nutritional factors that is widely consumed during early childhood development. However, it has been associated with allergic responses and immune cell activation. Here, we investigate whether cow’s milk consumption regulates gut–brain axis functions and affects patterns of behaviors in BALB/c mice, previously described by present low sociability, significant stereotypes, and restricted interest features. The major objectives consist of to investigate cow’s milk supplementation as possible triggers interfering with cellular niches of the gut–brain axis and behavioral patterns. Methods: Male BALB/c at 6 weeks were randomly divided into two groups, one supplemented with cow’s milk processed at ultra-high temperature (UHT) and another group receiving water (controls) three times per day (200 μL per dose) for one week. Results: Milk consumption disturbed histological compartments of the small intestine, including niches of KI67⁺-proliferating cells and CD138⁺ Ig-secreting plasma cells. In the liver, milk intake was associated with pro-inflammatory responses, oxidative stress, and atypical glycogen distribution. Milk-supplemented mice showed significant increase in granulocytes (CD11b⁺SSC^high cells) and CD4⁺ T cells in the blood. These mice also had neuroinflammatory signals, including an enhanced number of cortical Iba-1⁺ microglial cells in the brain and significant cerebellar expression of nitric oxide synthase 2 by Purkinje cells. These phenotypes and tissue disorders in milk-supplemented mice were associated with atypical behaviors, including low sociability, high restricted interest, and severe stereotypies. Moreover, synaptic niches were also disturbed after milk consumption, and Shank-3⁺ and Drebrin⁺ post-synaptic cells were significantly reduced in the brain of these mice. Conclusions: Together, these data suggest that milk consumption interfered with the gut–brain axis in BALB/c mice and increased atypical behaviors, at least in part, linked to synapse dysfunctions, neuroinflammation, and oxidative stress regulation. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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20 pages, 6161 KB

Open AccessArticle

First Application of a Mixed Porcine–Human Repopulated Bioengineered Liver in a Preclinical Model of Post-Resection Liver Failure

by Philipp Felgendreff, Seyed Mohammad Hosseiniasl, Anna Minshew, Bruce P. Amiot, Silvana Wilken, Boyukkhanim Ahmadzada, Robert C. Huebert, Nidhi Jalan Sakrikar, Noah G. Engles, Peggy Halsten, Kendra Mariakis, John Barry, Shawn Riesgraf, Chris Fecteau, Jeffrey J. Ross and Scott L. Nyberg

Biomedicines 2024, 12(6), 1272; https://doi.org/10.3390/biomedicines12061272 - 7 Jun 2024

Cited by 1 | Viewed by 2379

Abstract

In this study, a mixed porcine–human bioengineered liver (MPH-BEL) was used in a preclinical setup of extracorporeal liver support devices as a treatment for a model of post-resection liver failure (PRLF). The potential for human clinical application is further illustrated by comparing the functional capacity of MPH-BEL grafts as assessed using this porcine PRLF model with fully human (FH-BEL) grafts which were perfused and assessed in vitro. BEL grafts were produced by reseeding liver scaffolds with HUVEC and primary porcine hepatocytes (MPH-BEL) or primary human hepatocytes (FH-BEL). PRLF was induced by performing an 85% liver resection in domestic white pigs and randomized into the following three groups 24 h after resection: standard medical therapy (SMT) alone, SMT + extracorporeal circuit (ECC), and SMT + MPH-BEL. The detoxification and metabolic functions of the MPH-BEL grafts were compared to FH-BEL grafts which were perfused in vitro. During the 24 h treatment interval, INR values normalized within 18 h in the MPH-BEL therapy group and urea synthesis increased as compared to the SMT and SMT + ECC control groups. The MPH-BEL treatment was associated with more rapid decline in hematocrit and platelet count compared to both control groups. Histological analysis demonstrated platelet sequestration in the MPH-BEL grafts, possibly related to immune activation. Significantly higher rates of ammonia clearance and metabolic function were observed in the FH-BEL grafts perfused in vitro than in the MPH-BEL grafts. The MPH-BEL treatment was associated with improved markers of liver function in PRLF. Further improvement in liver function in the BEL grafts was observed by seeding the biomatrix with human hepatocytes. Methods to reduce platelet sequestration within BEL grafts is an area of ongoing research. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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Review

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14 pages, 771 KB

Open AccessReview

Gut Microbiome-Mediated Genetic and Epigenetic Alterations in Colorectal Cancer: Population-Specific Insights

by Simona Turcu, Florin Grama and Maria Gazouli

Biomedicines 2025, 13(9), 2262; https://doi.org/10.3390/biomedicines13092262 - 14 Sep 2025

Viewed by 1104

Abstract

Colorectal cancer (CRC) remains a major global challenge, with growing attention to its pathogenesis as mediated by the gut microbiome and epigenetic regulation. Despite therapeutic progress, clinical management remains difficult. CRC accounts for ~10% of cancers and is the second leading cause of cancer death worldwide. Romania bears a substantial burden, with many diagnoses at advanced stages. Etiology—Integrated Genetic, Environmental, and Microbial Determinants. Hereditary syndromes explain 10–15% of cases; most are sporadic, with hypermutated MSI/POLE (~15%), non-hypermutated chromosomal instability (~85%), and a CpG island methylator phenotype (~20%). GWAS implicate loci near SMAD7, TCF7L2, and CDH1; in Romania, SMAD7 rs4939827 associates with risk. Lifestyle exposures—high red/processed meat, low fiber, adiposity, alcohol, and smoking—shape susceptibility. Microbiome–Epigenome Interactions. Dysbiosis promotes carcinogenesis via genotoxins (e.g., colibactin), hydrogen sulfide, activation of NF-κB/STAT3, barrier disruption, and epigenetic remodeling of DNA methylation and microRNAs. Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and pks⁺ Escherichia coli exemplifies these links. Population-Specific Risk—Romania within Lifestyle–Microbiome Evidence. Incidence is rising, including early-onset disease. Romania lacks CRC-specific microbiome datasets. However, metabolic cohorts show loss of butyrate producers, enrichment of pathobionts, and SCFA imbalance—patterns that mirror European CRC cohorts—and exhibit regional heterogeneity. Beyond Fusobacterium nucleatum. Additional oncobacteria shape tumor biology. Peptostreptococcus stomatis activates integrin α6/β4→ERBB2–MAPK and can bypass targeted inhibitors, while Parvimonas micra enhances WNT/β-catenin programs and Th17-skewed immunity. Together, these data support a systems view in which microbial cues and host epigenetic control jointly drive CRC initiation, progression, metastasis, and treatment response. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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21 pages, 13796 KB

Open AccessReview

Linitis Plastica-like Metastases to the Gastrointestinal Tract on Cross-Sectional Imaging

by Ana Veron Sanchez, Elena Canales Lachen, Maria Gomez Galdon, Luigi Moretti, Calliope Maris, Ana Maria Bucalau, Charif Khaled and Maria Antonietta Bali

Biomedicines 2025, 13(9), 2197; https://doi.org/10.3390/biomedicines13092197 - 8 Sep 2025

Viewed by 598

Abstract

This review provides an overview of the cross-sectional imaging features of gastrointestinal (GI) metastases presenting with a linitis plastica (LP) pattern and illustrates these findings through a series of cases from various primary tumors. It also addresses key diagnostic challenges, with particular attention to differential diagnosis. The term linitis plastica (LP) refers to the macroscopic appearance of a hollow organ with diffuse mural tumor infiltration, leading to loss of parietal distensibility. Although rare, primary LP can occur throughout the gastrointestinal (GI) tract. First described in the stomach—the most common site—it is typically associated with undifferentiated adenocarcinoma composed of poorly cohesive cells, often with signet ring morphology. Beyond primary GI tumors, LP-like metastases may also arise from extragastrointestinal primaries, most notably breast carcinoma (particularly the lobular subtype), as well as urinary bladder and prostate carcinomas. LP-like GI metastases typically manifest as circumferential, enhancing wall thickenings with exaggerated zonal anatomy and luminal narrowing. Due to diffuse parietal tumor infiltration—often with mucosal preservation—the submucosa and serosa appear disproportionately thickened and show greater enhancement relative to the muscularis propria (MP). This specific imaging appearance is known as the malignant target sign, which must be distinguished from the benign target sign, where the most prominent low-density layer corresponds to edematous submucosa. Additional key features include homogeneous enhancement with loss of layer differentiation on delayed-phase imaging and a concentric ring pattern on MR. Secondary findings may also be present, such as intestinal obstruction and concomitant peritoneal carcinomatosis (PC). Gastrointestinal metastases with an LP pattern present a significant diagnostic challenge, as they can mimic both primary tumors and benign inflammatory or infectious conditions. Accurate diagnosis is critical because management strategies differ substantially. Since the mucosa is often spared, endoscopy and superficial biopsies may yield false-negative results. Therefore, while immunohistochemistry (IHC) remains essential for confirmation, radiologists play a pivotal role in raising suspicion for LP-like GI metastases and recommending deep, extensive biopsies to obtain adequate representative tissue. Furthermore, in cases of an unknown primary tumor, recognition of the LP pattern can provide important clues to the potential site of origin. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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22 pages, 3709 KB

Open AccessReview

Unraveling Chylomicron Retention Disease Enhances Insight into SAR1B GTPase Functions and Mechanisms of Actions, While Shedding Light of Intracellular Chylomicron Trafficking

by Emile Levy, Catherine Fallet-Bianco, Nickolas Auclair, Natalie Patey, Valérie Marcil, Alain Théophile Sané and Schohraya Spahis

Biomedicines 2024, 12(7), 1548; https://doi.org/10.3390/biomedicines12071548 - 12 Jul 2024

Cited by 1 | Viewed by 2325

Abstract

Over the past three decades, significant efforts have been focused on unraveling congenital intestinal disorders that disrupt the absorption of dietary lipids and fat-soluble vitamins. The primary goal has been to gain deeper insights into intra-enterocyte sites, molecular steps, and crucial proteins/regulatory pathways involved, while simultaneously identifying novel therapeutic targets and diagnostic tools. This research not only delves into specific and rare malabsorptive conditions, such as chylomicron retention disease (CRD), but also contributes to our understanding of normal physiology through the utilization of cutting-edge cellular and animal models alongside advanced research methodologies. This review elucidates how modern techniques have facilitated the decoding of CRD gene defects, the identification of dysfunctional cellular processes, disease regulatory mechanisms, and the essential role of coat protein complex II-coated vesicles and cargo receptors in chylomicron trafficking and endoplasmic reticulum (ER) exit sites. Moreover, experimental approaches have shed light on the multifaceted functions of SAR1B GTPase, wherein loss-of-function mutations not only predispose individuals to CRD but also exacerbate oxidative stress, inflammation, and ER stress, potentially contributing to clinical complications associated with CRD. In addition to dissecting the primary disease pathology, genetically modified animal models have emerged as invaluable assets in exploring various ancillary aspects, including responses to environmental challenges such as dietary alterations, gender-specific disparities in disease onset and progression, and embryonic lethality or developmental abnormalities. In summary, this comprehensive review provides an in-depth and contemporary analysis of CRD, offering a meticulous examination of the CRD current landscape by synthesizing the latest research findings and advancements in the field. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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13 pages, 1605 KB

Open AccessReview

Progastrin: An Overview of Its Crucial Role in the Tumorigenesis of Gastrointestinal Cancers

by Rodanthi Fioretzaki, Panagiotis Sarantis, Nikolaos Charalampakis, Konstantinos Christofidis, Adam Mylonakis, Evangelos Koustas, Michalis V. Karamouzis, Stratigoula Sakellariou and Dimitrios Schizas

Biomedicines 2024, 12(4), 885; https://doi.org/10.3390/biomedicines12040885 - 17 Apr 2024

Cited by 1 | Viewed by 2182

Abstract

Defining predictive biomarkers for targeted therapies and optimizing anti-tumor immune response is a main challenge in ongoing investigations. Progastrin has been studied as a potential biomarker for detecting and diagnosing various malignancies, and its secretion has been associated with cell proliferation in the gastrointestinal tract that may promote tumorigenesis. Progastrin is a precursor molecule of gastrin, synthesized as pre-progastrin, converted to progastrin after cleavage, and transformed into amidated gastrin via biosynthetic intermediates. In cancer, progastrin does not maturate in gastrin and becomes a circulating and detectable protein (hPG80). The development of cancer is thought to be dependent on the progressive dysregulation of normal signaling pathways involved in cell proliferation, thus conferring a growth advantage to the cells. Understanding the interaction between progastrin and the immune system is essential for developing future cancer strategies. To that end, the present review will approach the interlink between gastrointestinal cancers and progastrin by exploring the underlying molecular steps involved in the initiation, evolution, and progression of gastrointestinal cancers. Finally, this review will focus on the clinical applications of progastrin and investigate its possible use as a diagnostic and prognostic tumor circulating biomarker for disease progression and treatment effectiveness, as well as its potential role as an innovative cancer target. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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16 pages, 505 KB

Open AccessSystematic Review

Effects of Nicotine-Free E-Cigarettes on Gastrointestinal System: A Systematic Review

by Ivana Jukic, Ivona Matulic and Jonatan Vukovic

Biomedicines 2025, 13(8), 1998; https://doi.org/10.3390/biomedicines13081998 - 16 Aug 2025

Viewed by 1462

Abstract

Background/Objectives: Nicotine-free electronic cigarettes (NFECs) are becoming increasingly popular, especially among youth and non-smokers, yet their effects on the gastrointestinal tract (GIT) remain poorly understood. This systematic review synthesizes available in vitro, in vivo, and limited human evidence on NFEC-associated changes in gastrointestinal health and function. Methods: Literature searches were conducted in Medline, Web of Science, Cochrane, and Scopus in July 2025, following PRISMA guidelines. Eligible studies examined NFEC effects on any GIT segment, including the oral cavity, liver, intestines, and microbiome. Data on study design, exposure characteristics, and main outcomes were extracted and narratively synthesized. Results: Of 111 identified records, 94 full-text articles were retrieved, and 21 studies met the inclusion criteria. Most were preclinical, with only one human pilot study. Evidence from oral cell and microbial models suggests that NFEC aerosols can induce pro-inflammatory cytokine production, impair cell viability, and disrupt microbial metabolism through their base constituents (propylene glycol, vegetable glycerine, and flavourings). Animal studies indicate possible hepatic oxidative stress, altered lipid metabolism, and gut barrier dysfunction, with some data suggesting more pronounced steatosis in nicotine-free exposures compared to nicotine-containing counterparts. Microbiome studies report reduced tight junction expression and altered neutrophil function. Conclusions: Current evidence is limited and predominantly preclinical but indicates that NFEC exposure can affect multiple aspects of gastrointestinal health. Robust longitudinal and interventional human studies are urgently needed to determine the clinical relevance of these findings and to inform regulation and public health policy. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Gastrointestinal Tract Disease)

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