GLP-1-based drugs are approved for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 60% of patients with T2DM, and the gut microbiome plays a critical role in its pathogenesis. The gut–liver axis represents a key mechanistic link between dysbiosis and hepatic steatosis. A narrative literature review was conducted using PubMed, Scopus, and ClinicalTrials.gov (2015–2026). Search terms included “GLP-1 receptor agonist,” “microbiome,” “MASLD,” “MASH,” “NAFLD,” “NASH,” “liraglutide,” “semaglutide,” “tirzepatide,” “dulaglutide,” and “exenatide.” Of 363 identified articles, 330 were excluded due to duplication or non-relevant study design; 33 studies (18 preclinical, 15 clinical) were included. In preclinical models, liraglutide demonstrated normalization of the Firmicutes/Bacteroidetes ratio and increased Bifidobacterium and Lactobacillus spp., while tirzepatide significantly reduced hepatic steatosis and increased Akkermansia abundance in diabetic mice. Semaglutide improved gut barrier integrity, increased Alloprevotella and Alistipes, and ameliorated MASLD in murine models. In clinical studies, tirzepatide achieved MASH resolution in 44–62% of patients in the phase 2 SYNERGY-NASH trial. In August 2025, the FDA approved semaglutide for MASH with fibrosis based on the Phase 3 ESSENCE trial. A recent longitudinal study in T2DM patients showed that baseline microbiome composition predicted glycemic response to semaglutide, without significant changes in microbiome diversity. In conclusion, GLP-1-based therapies demonstrate consistent preclinical associations with gut microbiome modulation and reduction in hepatic steatosis. Baseline microbiome composition has been suggested as a potential predictor of treatment response, supporting a personalized approach to MASLD management and warranting future clinical studies.

Purpose: This pilot study was designed to investigate the impact of a moderate-calorie Mediterranean diet compared to a regular diet with omega-3 PUFAs (eicosapentaenoic and docosahexaenoic acids) supplementation on fatigue symptoms in patients with relapsing-remitting multiple sclerosis (RRMS) and to assess the optional benefit of the diet on their quality of life. Material/Methods: This 12-month pilot study was conducted in 2021 at the Department of Neurology, Medical University – Pleven, Bulgaria. A total of 60 patients with RRMS aged 18-64 were selected from the database of the Neurology Clinic at the University Hospital "Dr Georgi Stranski" – Pleven. From the selected patients, only 30 were included in the pilot phase and respectively assigned to the nutritional arms. Blood samples were collected twice – at the first and second visit in 3 months, for metabolic and dietary parameters analysis. Symptoms of fatigue were assessed with Fatigue Scale for Motor and Cognitive Functions (FSMC) and Modified Fatigue Impact Scale (MFIS). Results: From the 30 participants included in the study, 17 patients attended the clinic centre for complete follow-up; the remaining 13 were only partially observed. The dynamics of the followed-up parameters showed a statistically significant change in the body mass index (BMI), the fatigue symptoms in the FSMC and MFIS scales, total cholesterol and triglycerides levels, and the serum concentrations of IL17A, EPA and DHA. The metabolic caloric values were also found to be significantly changed. Conclusions: Despite the small study size limitation, this pilot study might be of benefit for further extensive research on the potential favorable impact of diet and lifestyle modifications on the symptoms of fatigue in multiple sclerosis patients.

Objective: Mitochondria drive cellular energy production and regulate key biological processes. High levels of heteroplasmic in mitochondrial DNA (mtDNA) variants can cause mitochondrial dysfunction and clinical symptoms. Third-generation sequencing overcomes the limitations of traditional mtDNA analysis methods, offering improved cost, throughput, and sensitivity. We developed an integrated approach for analyzing methylation patterns and genetic variations in mtDNA and ADME genes. Methods: We implemented Oxford Nanopore’s long-read sequencing with adaptive sampling (AS) to enrich enzymatically linearized mtDNA and absorption, distribution, metabolism, and excretion (ADME) genes without PCR amplification, enabling native sequencing in adipose-derived mesenchymal stem cells (AdMSC). Our custom algorithm preserved phase relationships between base modifications and sequence polymorphisms. Results: We identified differential methylation patterns in ADME genes correlating with specific genetic variants, suggesting epigenetic regulation of drug response. Adaptive sampling identifies a wider range of variant diversity, while whole genome sequencing (WGS) uncovers higher-frequency hotspots. Both methods offer complementary insights into mitochondrial heteroplasmy. In mtDNA, direct sequencing showed extensive hypomethylation, and low levels of non-CpG methylation were detected regardless of sequencing coverage depth. These sparse methylation patterns showed non-random distribution, correlating with functional regions and heteroplasmic sites. Conclusions: This study demonstrates the utility of adaptive sampling for the integrated analysis of mtDNA heteroplasmy and native base modifications, revealing widespread hypomethylation independent of coverage depth. The approach showcases the potential for combined pharmacoepigenomic and mitochondrial profiling in precision medicine, disease modeling, and therapeutic development.

Antimicrobial resistance threatens the very core of modern medicine and currently costs the EU more than 11.7 billion euro per year. In 2050 it is projected that 10 million people will die from infections with the so called “superbugs”. In the past few decades, no entirely new antibiotic groups are being discovered which makes of crucial importance to preserve the effectiveness of the antibiotics we have today for future generations. Antimicrobial stewardship programs worldwide aim to optimize the use of antimicrobials to improve effectiveness, safety and economic feasibility of antibiotics while fighting antibiotic resistance on a local and global scale. This article shares the experience of building a software solution from scratch for digitalisation of local antibiotic stewardship policies – what are the key features needed and the steps required for successful implementation of a digital local antibiotic stewardship policy and who are the stakeholders in a project of this nature.

The NLRP3 inflammasome is a key sensor of cellular stress and pathogen-associated signals in the innate immune system. Using confocal fluorescence microscopy in microvascular lung endothelial cells, we examined ASC speck formation following expression of the SARS-CoV-2 ORF3a protein. ORF3a engaged caspase-1 through dual architectural modes: alongside the canonical pyroptosome-like pathway, a novel distributed, multifocal inflammasome pathway emerged. Multiple ASC specks were observed at later time points, yet caspase-1 activation could occur in their absence, indicating that visible speck assembly is not strictly required for inflammasome signalling. These observations provide insight into the spatiotemporal dynamics of ASC during viral protein expression. The findings contribute to a better understanding of NLRP3 inflammasome regulation under conditions of viral replication.