MF VSI Klinikinės ir molekulinės gastroenterologijos laboratorija (04.06.02)

Quinones are natural compounds widely distributed in animals, plants, and microorganisms, where they play essential roles in cellular energy metabolism. Ascorbate (vitamin C) can exert antioxidant or pro-oxidant effects depending on concentration and cellular context. Studies have shown that quinones can undergo redox cycling, leading to the generation of reactive oxygen species (ROS), a process that is further enhanced in the presence of ascorbate. Due to the elevated production of reactive oxygen species (ROS) and compromised antioxidant defenses in cancer cells, redox imbalance has been proposed as a potential "Achilles' heel" of tumors. In this context, the combination of ascorbate and quinones represents a promising strategy for selectively targeting cancer cells through enhanced ROS generation. This review discusses the mechanisms and biological effects of natural and synthetic quinoid compounds, particularly their interactions with ascorbate in cancer cells.

Background and aims.
The use of large language models (LLMs), such as ChatGPT, is rapidly expanding in clinical medicine but data in gastroenterology are limited. We aimed to assess the prevalence and patterns of LLM use among European gastroenterologists, evaluate perceived benefits and risks and identify barriers and priorities for future integration.
Methods.
A Europe-wide online survey was conducted between June and August 2025. A 24-item questionnaire was distributed via national gastroenterology societies and social media. Questions on specific applications, reliability and clinical impact were shown only to respondents with prior LLM experience.
Results.
A total of 966 gastroenterologists from 34 European countries responded, 55.3% reported using LLMs, mainly weekly (54.4%) or daily (20.2%). Common uses included education (59.2%), clinical decision support (58.2%) and scientific writing (39.1%). Among academic users, summarisation (80.1%) and grammar refinement (74.4%) were most frequent. Most users rated LLMs as moderately or highly reliable (81.0%), and 84.3% believed they improve outcomes. Nearly two-thirds (64.5%) felt LLMs can support endoscopy practice. Inaccuracies were reported by 42.7% and were associated with lower trust (ρ=–0.40, p<0.001). Although only 7.8% had formal training, 90.0% supported structured education and 85.2% favoured curricular integration. Most respondents would recommend LLM use (91.4%) and expect broader adoption within 5 years (93.4%). Reported barriers included institutional regulations (45.7%), cost (36.1%), complexity (29.4%) and time constraints (27.9%).
Conclusion.
LLMs are increasingly integrated into clinical and academic workflows in European gastroenterology. Structured training, specialty-specific development and clear governance are essential for safe implementation.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a public health threat in Europe. With an estimated 30.4% prevalence among the adult population in the European Union and United Kingdom, it is the most common chronic liver disease and is closely linked to obesity and type 2 diabetes, which can be considered as indicator conditions. Despite the scale of the burden, the spectrum of MASLD, including its advanced form, metabolic dysfunction-associated steatohepatitis (MASH), is weakly represented—or even absent—from health policy and development agendas. Further, the extent to which regional and national clinical practice guidelines (CPGs) on other liver diseases and related fields incorporate information on MASLD/MASH prevention or management is unclear. In this Series paper, we reviewed policy attention to MASLD/MASH across the European Union and the United Kingdom. We report low policy readiness across European countries to address MASLD/MASH. Only two (7.1%), Romania and Sweden, had a subnational strategy, while 13 (46.4%) referenced MASLD/MASH in other national or subnational action plans, predominantly those for liver disease and obesity. No country included MASLD/MASH in its priority non-communicable disease list. Additionally, 15 (53.6%) countries had national MASLD/MASH CPGs, while 25 (89.3%) mentioned MASLD/MASH in other national CPGs, most often those for obesity, diabetes, cirrhosis, liver transplantation, and primary care, respectively. We conclude that MASLD/MASH remains insufficiently addressed from a policy perspective, which contributes to low readiness to address this public health threat.

Mitochondria are essential cellular organelles that were first identified in the mid-19th century. Despite more than 150 years of research and the accumulation of vast wealth of knowledge on mitochondrial structure and functions, new breakthroughs are still being made in recent years in key areas of mitochondrial biology. In the field of cancer research, major progress includes the elucidation of the role of mitochondria in cancer metabolic reprogramming, the discovery of signaling pathways in the crosstalk between mitochondria and the nucleus, the revelation of significant mitochondrial impact on tumor microenvironment and immune cells, the realization of the intriguing interplay between gut microbiota and cancer metabolism, the identification of molecular targets in mitochondria and the related pathways, and the development of mitochondria-targeted drugs such as mitocans for cancer treatment. This new progress underscores the essential role of mitochondria as multifaceted regulators of cancer metabolism, signal transduction, and cell survival, and as key pharmacological targets. This article will provide an up-to-date review of these important areas. The implications of these new research advances in cancer pharmacology and therapeutics will be explored, and interesting concepts that provide alternative theories for bioenergetics will also be discussed. SIGNIFICANCE STATEMENT: As a central hub for cellular energy production and biomolecule metabolism, mitochondria play essential roles in regulating metabolic and redox homeostasis, significantly affecting cell proliferation, survival, and sensitivity to pharmacological agents. Dysfunction of mitochondria in cancer cells alters these vital processes and affects tumor growth and therapeutic responses. Thus, a comprehensive understanding of mitochondrial alterations, the underlying regulatory mechanisms, and their impacts on pharmacological targets is pivotal for developing more effective therapeutic agents with significant clinical implications in cancer treatment.

Collagenous colitis (CC) is diagnosed histologically and is characterised by a thickened subepithelial collagen band together with inflammatory and epithelial changes. Although routine haematoxylin and eosin (H&E) staining is sufficient for diagnosis in most cases, visual assessment of the collagen band can be challenging in borderline or heterogeneous specimens. Additional stains may be required in diagnostically difficult situations.

Late diagnosis and the lack of effective early detection techniques contribute to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). To address this challenge, we develop ¹H NMR-based metabolomics-AI platforms employing customized multilayer support vector machine (SVM), AutoGluon, and Tabular Foundation Model (TabPFN) frameworks. These platforms integrate serum metabolomic profiles-including small-molecule metabolites and lipoproteins-with clinical/biochemical parameters (age, CA19-9) and Activin A, derived from 902 participants (424 high-risk controls and 478 PDAC cases). Our TabPFN-based algorithm, PanMETAI, outperform state-of-the-art models. In the Taiwanese training and validation cohort, the model achieved an impressive AUC of 0.99 (95% CI: 0.98-0.99). Its robustness is further confirmed in a Lithuanian external validation cohort (n = 322), which yields an AUC of 0.93 (0.90-0.95). Notably, it identifies key signature patterns that improve early-stage (I/II) PDAC diagnosis and perform well with small sample sizes (n = 50). TabPFN-PanMETAI offers a rapid, accurate, and non-invasive tool for early PDAC detection, with strong potential for clinical application.

Mitochondrial structural and functional changes accompany psoriasis, yet the mitochondrial response to psoriatic inflammation in keratinocytes and fibroblasts remains unexplored. In this study, we investigated the effect of psoriasis-like inflammation (PLI) induced by a cytokine cocktail (interleukin (IL)-17A, IL-22 and tumour necrosis factor (TNF)-α) on mitochondrial network morphology and function in cultured keratinocytes (HaCaT) and fibroblasts (BJ-5ta). In both cell types, PLI triggered the expression of psoriasis-related Elafin and high amounts of cytokines (IL-1, IL-6), interferons (IFN-α, IFN-β, IFN-γ), and chemokines (C-C motif chemokine 5 (CCL5) and IL-8), accompanied by increased mitochondrial membrane potential, reactive oxygen species (ROS) production, respiration suppression, network fragmentation, swelling and cristae disassembly. Stimulated emission depletion (STED) nanoscopy revealed the disappearance of mitochondrial cristae in response to PLI, with the process starting more quickly and being more pronounced in keratinocytes than in fibroblasts. These findings highlight cell-specific mitochondrial responses to psoriatic inflammation, guiding future investigations towards new pharmacological targets for managing psoriasis.

Background Collagenous colitis (CC) is a form of microscopic colitis (MC) and is characterized by chronic watery diarrhoea and urgency sometimes leading to incontinence resulting in significantly decreased quality of life1. MC is thought to develop due to a pathological immune response to intestinal luminal antigens in genetically predisposed individuals2. Intestinal microbiota is thought to play a key role in the pathogenesis of MC3. However, neither the pathogenesis of MC nor the role of microbiota in its development are fully understood. The aim of our study was to create a mouse model of CC using faecal microbiota transplantation (FMT) in order to gain further insight into the role of gut microbiota in MC pathogenesis.

Methods In the model we used C57BL/6 mice (8 weeks old) across seven treatment groups (n = 10/group). This included 2 control groups (one receiving no FMT and one receiving FMT from healthy controls) and 5 groups receiving FMT prepared from different CC donors. The FMT was performed via enema after broad spectrum antibiotic treatment and bowel cleansing. Afterwards the mice received FMT daily via the oral route. The mice were followed up for 24 weeks. Blood analysis and 16S rRNA sequencing of fecal samples were performed at multiple time points. At the end of the experiment, histological analysis of the animals’ digestive tract was performed.

Results
Significant decreases in alpha diversity (Shannon) and alterations in bacterial composition were observed across all groups after antibiotic treatment. Beta diversity analysis at different timepoints revealed that mouse microbiome composition steadily drifted towards baseline across all groups (figure 1), with donor microbiota accounting for a small fraction (<1-2 %) by week 24 across all FMT groups. Throughout the experiment, microbiota changes exhibited significant heterogeneity within groups, with individual differences, rather than FMT, being the primary factor. Immune cell analysis in the blood showed a dynamic pattern: white blood cell and lymphocyte counts declined initially, peaked at 8 weeks, and stabilized by 24 weeks. Granulocyte levels fluctuated markedly, reaching their highest point at 16 weeks, whereas monocyte counts remain stable throughout. Histological analysis revealed no morphological changes of the mice digestive tract across all groups.

Conclusion FMT from CC donors failed to induce inflammatory changes in mice.

Background: The intestinal microbiota-tryptophan metabolism axis is an important regulator in inflammatory bowel disease (IBD)1 . Gut bacteria convert tryptophan into bioactive metabolites, which act on intestinal cells through the aryl hydrocarbon receptor (AHR)2 . These microbially derived metabolites are known to support mucosal homeostasis2 , yet their direct impact on epithelial barrier responses in Crohn’s disease (CD) compared with non-IBD under inflammatory and non-inflammatory conditions, remains underexplored. Methods: Intestinal epithelial organoids were generated from caecal biopsies of CD patient and non-IBD donor and differentiated for four days. Inflammation was induced with IFN-γ and TNF-α (10ng/mL each, 24h). Tryptophan, tryptamine, nicotinamide, indole-3-acetic acid, and indole-3-propionic acid were applied individually 1h before cytokine exposure and maintained throughout; non-inflamed organoids were exposed for 25h. Working concentration of each metabolite was determined by Caco-2 screening. Total RNA was analyzed by RT-qPCR. Expression of three functional gene groups was evaluated: inflammatory (CXCL9,TNF, IL1B), AHR/xenobiotic metabolism (AHR, UGT1A1, CYP1A1), and barrier-related (TJP1, CLDN1,OCLN, MUC2, LGR5, KI67). Data were processed in RStudio, statistical significance level was set to padj. ≤ 0.05. Results: In non-inflamed CD organoids, tryptophan metabolites induced AHR pathway genes such as CYP1A1 and UGT1A1, showing increases of approximately 5-8 log2 FC, but did not increase barrier-related transcripts. Inflammatory stimulation strongly upregulated CXCL9, IL1B, and TNF, with increases of approximately 5-11 log2 FC, while reducing barrier markers expression by about 1-2 log2 FC. Metabolite co-treatment during inflammation maintained AHR activation and partially restored OCLN expression by about 0.6-0.8 log2 FC. In non-IBD organoids, metabolites upregulated both AHR-related genes such as CYP1A1, with increases of approximately 5-7 log2 FC, and barrier genes including CLDN1, OCLN, MUC2, and LGR5, which rose by about 1-2 log2 FC. Inflammation caused weaker immune activation than in CD and moderately reduced barrier genes, while metabolite treatment partly restored OCLN expression by about 0.5-0.7 log2 FC, with limited effects on other barrier markers. Although trends were consistent, not all log2 FC values were statistically significant. Conclusion: In conclusion, microbially derived tryptophan metabolites activate epithelial AHR signaling in both CD and non-IBD organoids, but barrier regulation differs. Therefore, our results indicate diagnosis-specific epithelial sensitivity to microbial products.

Background: The incidence and prevalence of inflammatory bowel disease (IBD) are rising worldwide. The 2010 European inception cohort study demonstrated a gradient (2:1) between Western and Eastern European countries. At that time, the incidence of IBD in the Kaunas region of Lithuania was 8.5 per 100,000 population (6.1 for UC and 2.4 for CD). Recent data from Central and Eastern Europe remain limited, although clinical practice suggests a possible increase in IBD burden. This study aimed to describe contemporary epidemiological trends of ulcerative colitis (UC) and Crohn’s disease (CD) in Lithuania using national administrative datasets. Methods: A retrospective, population-based study was conducted using anonymized data from the Lithuanian State Data Reuse Platform for 2020–2024. All residents with at least one recorded UC or CD diagnosis were included. Incident cases were identified by the first disease entry following a three-year lookback period. Annual crude incidence and prevalence rates per 100,000 population were calculated. Trends in hospitalizations and pharmacological treatment were analyzed descriptively. Results: In total, 5601 UC and 1500CD cases were identified. The mean annual UC incidence was 20.2 per 100,000 (17.5, 19.9, 22.8, 21.9, and 20.2 for 2020–2024, respectively), and the mean annual prevalence was 131.2 per 100,000. For CD, the mean annual incidence was 6.4 (5.3, 5.9, 7.4, 6.5, 7.0 for 2020–2024, respectively), and the mean annual prevalence was 31.8 per 100,000. The mean age at diagnosis was 42 years (SD 18.6) for UC and 38 years (SD 19.9) for CD. Mean annual hospitalization rates were 10.6% for UC and 17.8% for CD, remaining stable throughout 2020–2024. The use of advanced therapies among UC patients increased from 4% in 2020 to 11% in 2024, and among CD patients from 19% to 26% over the same period. Conclusion: Our data show significantly higher IBD incidence and prevalence rates in Lithuania compared to those reported in 2007–2010. The use of advanced therapies continued to rise, whereas hospitalization rates remained stable.