Correction: Stofilová et al. Probiotic-Based Intervention in the Treatment of Ulcerative Colitis: Conventional and New Approaches. Biomedicines 2022, 10, 2236.

The authors would like to add the following clarification regarding the clinical trials evaluating the probiotic product VSL#3 cited in the published paper [...].

Differentially Expressed Genes Induced by Erythropoietin Receptor Overexpression in Rat Mammary Adenocarcinoma RAMA 37-28 Cells.

The erythropoietin receptor (EPOR) is a transmembrane type I receptor with an essential role in the proliferation and differentiation of erythroid progenitors. Besides its function during erythropoiesis, EPOR is expressed and has protective effect in various non-hematopoietic tissues, including tumors. Currently, the advantageous aspect of EPOR related to different cellular events is still under scientific investigation. Besides its well-known effect on cell proliferation, apoptosis and differentiation, our integrative functional study revealed its possible associations with metabolic processes, transport of small molecules, signal transduction and tumorigenesis. Comparative transcriptome analysis (RNA-seq) identified 233 differentially expressed genes (DEGs) in EPOR overexpressed RAMA 37-28 cells compared to parental RAMA 37 cells, whereas 145 genes were downregulated and 88 upregulated. Of these, for example, GPC4, RAP2C, STK26, ZFP955A, KIT, GAS6, PTPRF and CXCR4 were downregulated and CDH13, NR0B1, OCM2, GPM6B, TM7SF3, PARVB, VEGFD and STAT5A were upregulated. Surprisingly, two ephrin receptors, EPHA4 and EPHB3, and EFNB1 ligand were found to be upregulated as well. Our study is the first demonstrating robust differentially expressed genes evoked by simple EPOR overexpression without the addition of erythropoietin ligand in a manner which remains to be elucidated.

Beneficial Effect of Faecal Microbiota Transplantation on Mild, Moderate and Severe Dextran Sodium Sulphate-Induced Ulcerative Colitis in a Pseudo Germ-Free Animal Model.

Transplantation of faecal microbiota (FMT) is generally considered a safe therapeutic procedure with few adverse effects. The main factors that limit the spread of the use of FMT therapy for idiopathic inflammatory bowel disease (IBD) are the necessity of minimising the risk of infection and transfer of another disease. Obtaining the animal model of UC (ulcerative colitis) by exposure to DSS (dextran sodium sulphate) depends on many factors that significantly affect the result. Per os intake of DSS with water is individual for each animal and results in the development of a range of various forms of induced UC. For this reason, the aim of our study was to evaluate the modulation and regenerative effects of FMT on the clinical and histopathological responses and the changes in the bowel microenvironment in pseudo germ-free (PGF) mice of the BALB/c line subjected to chemical induction of mild, moderate and serious forms of UC. The goal was to obtain new data related to the safety and effectiveness of FMT that can contribute to its improved and optimised use. The animals with mild and moderate forms of UC subjected to FMT treatment exhibited lower severity of the disease and markedly lower damage to the colon, including reduced clinical and histological disease index and decreased inflammatory response of colon mucosa. However, FMT treatment failed to achieve the expected therapeutic effect in animals with the serious form of UC activity. The results of our study indicated a potential safety risk involving development of bacteraemia and also translocation of non-pathogenic representatives of bowel microbiota associated with FMT treatment of animals with a diagnosed serious form of UC.

Probiotics and postbiotics in colorectal cancer: Prevention and complementary therapy.

Colorectal cancer (CRC) is a leading cause of human mortality worldwide. As conventional anticancer therapy not always being effective, there is growing interest in innovative "drug-free" cancer treatments or interventions that improve the efficacy of established therapy. CRC is associated with microbiome alterations, a process known as dysbiosis that involves depletion and/or enrichment of particular gut bacterial species and their metabolic functions. Supplementing patient treatment with traditional probiotics (with or without prebiotics), next-generation probiotics (NGP), or postbiotics represents a potentially effective and accessible complementary anticancer strategy by restoring gut microbiota composition and/or by signaling to the host. In this capacity, restoration of the gut microbiota in cancer patients can stabilize and enhance intestinal barrier function, as well as promote anticarcinogenic, anti-inflammatory, antimutagenic or other biologically important biochemical pathways that show high specificity towards tumor cells. Potential benefits of traditional probiotics, NGP, and postbiotics include modulating gut microbiota composition and function, as well as the host inflammatory response. Their application in CRC prevention is highlighted in this review, where we consider supportive in vitro, animal, and clinical studies. Based on emerging research, NGP and postbiotics hold promise in establishing innovative treatments for CRC by conferring physiological functions via the production of dominant natural products and metabolites that provide new host-microbiota signals to combat CRC. Although favorable results have been reported, further investigations focusing on strain and dose specificity are required to ensure the efficacy and safety of traditional probiotics, NGP, and postbiotics in CRC prevention and treatment.

Probiotic-Based Intervention in the Treatment of Ulcerative Colitis: Conventional and New Approaches.

Although there are number of available therapies for ulcerative colitis (UC), many patients are unresponsive to these treatments or experience secondary failure during treatment. Thus, the development of new therapies or alternative strategies with minimal side effects is inevitable. Strategies targeting dysbiosis of gut microbiota have been tested in the management of UC due to the unquestionable role of gut microbiota in the etiology of UC. Advanced molecular analyses of gut microbiomes revealed evident dysbiosis in UC patients, characterized by a reduced biodiversity of commensal microbiota. Administration of conventional probiotic strains is a commonly applied approach in the management of the disease to modify the gut microbiome, improve intestinal barrier integrity and function, and maintain a balanced immune response. However, conventional probiotics do not always provide the expected health benefits to a patient. Their benefits vary significantly, depending on the type and stage of the disease and the strain and dose of the probiotics administered. Their mechanism of action is also strain-dependent. Recently, new candidates for potential next-generation probiotics have been discovered. This could bring to light new approaches in the restoration of microbiome homeostasis and in UC treatment in a targeted manner. The aim of this paper is to provide an updated review on the current options of probiotic-based therapies, highlight the effective conventional probiotic strains, and outline the future possibilities of next-generation probiotic and postbiotic supplementation and fecal microbiota transplantation in the management of UC.

Synthesis of Novel Biologically Active Proflavine Ureas Designed on the Basis of Predicted Entropy Changes.

A novel series of proflavine ureas, derivatives 11a-11i, were synthesized on the basis of molecular modeling design studies. The structure of the novel ureas was obtained from the pharmacological model, the parameters of which were determined from studies of the structure-activity relationship of previously prepared proflavine ureas bearing n-alkyl chains. The lipophilicity (LogP) and the changes in the standard entropy (ΔS°) of the urea models, the input parameters of the pharmacological model, were determined using quantum mechanics and cheminformatics. The anticancer activity of the synthesized derivatives was evaluated against NCI-60 human cancer cell lines. The urea derivatives azepyl 11b, phenyl 11c and phenylethyl 11f displayed the highest levels of anticancer activity, although the results were only a slight improvement over the hexyl urea, derivative 11j, which was reported in a previous publication. Several of the novel urea derivatives displayed GI50 values against the HCT-116 cancer cell line, which suggest the cytostatic effect of the compounds azepyl 11b-0.44 µM, phenyl 11c-0.23 µM, phenylethyl 11f-0.35 µM and hexyl 11j-0.36 µM. In contrast, the novel urea derivatives 11b, 11c and 11f exhibited levels of cytotoxicity three orders of magnitude lower than that of hexyl urea 11j or amsacrine.

Co-Encapsulated Synbiotics and Immobilized Probiotics in Human Health and Gut Microbiota Modulation.

Growing interest in the development of innovative functional products as ideal carriers for synbiotics, e.g., nutrient bars, yogurt, chocolate, juice, ice cream, and cheese, to ensure the daily intake of probiotics and prebiotics, which are needed to maintain a healthy gut microbiota and overall well-being, is undeniable and inevitable. This review focuses on the modern approaches that are currently being developed to modulate the gut microbiota, with an emphasis on the health benefits mediated by co-encapsulated synbiotics and immobilized probiotics. The impact of processing, storage, and simulated gastrointestinal conditions on the viability and bioactivity of probiotics together with prebiotics such as omega-3 polyunsaturated fatty acids, phytochemicals, and dietary fibers using various delivery systems are considered. Despite the proven biological properties of synbiotics, research in this area needs to be focused on the proper selection of probiotic strains, their prebiotic counterparts, and delivery systems to avoid suppression of their synergistic or complementary effect on human health. Future directions should lead to the development of functional food products containing stable synbiotics tailored for different age groups or specifically designed to fulfill the needs of adjuvant therapy.

Toxicological evaluation of fluorescent 11-mercaptoundecanoic gold nanoclusters as promising label-free bioimaging probes in different cancer cell lines.

Due to advancement in nanomaterials and increasing use of functionalized gold nanoclusters (AuNCs) in different biomedical applications, better understanding of their potential cytotoxicity is necessary. Interactions of ultra-small fluorescent AuNCs with mammalian cells remains up to this day poorly understood, therefore, cytotoxic evaluation of thoroughly characterized ca. 2.5 nm spherical water-soluble 11-mercaptoundecanoic acid coated AuNCs (AuNC@M) with diverse fluorescent properties in variety of mammalian cancer cell lines was performed. Cell viability was assessed by traditional MTT assay and xCELLigence real time cell analyzer. Cell apoptosis was evaluated via an Annexin V-FITC/propidium iodide (PI) assay. Confocal fluorescence imaging confirmed that tested AuNC@M entered live cells and were homogeneously distributed in their cytoplasm. The results suggested that the cytotoxicity of tested nanoclusters was very low, or near the control level at concentrations 0.1 and 0.5 mg/mL in the cell lines after 24 h exposition. The purity of tested AuNC@M had no relevant effect on cell viability and no differences were observed after 24 h in our study. The low toxicity toward cancer cells further strengthens our view that AuNC@M are promising label-free fluorescent probes for bio-labelling and bio-imaging, or they can even serve as platforms for antitumor drug delivery systems.