Institute for Medical Biology

Metallofullerenols (MFs), functionalized endohedral fullerenes, exhibit unique activity by integrating atomic, molecular, and supramolecular levels of matter organization. The antioxidant properties of MFs constitute a novel technology, utilizing these nanocompounds for radioprotection. This integration of nanotechnology with radiological protection may contribute to revolutionary solutions in nuclear safety. Preclinical studies demonstrate low toxicity of MFs and high therapeutic value as redox mediators. In this study, the interaction of the metallofullerenol Sc3N@C80(OH)18 with high‐energy radiation and reactive oxygen species (ROS) is explored, laying the foundation for applications in modern cancer therapy. Radioprotective assessments are conducted on human erythrocytes exposed to gamma (γ) radiation. The rate constant determined by pulse radiolysis for reaction of Sc3N@C80(OH)18 with CCl3OO• radicals is 1.29 × 107 dm3 mol−1 s−1. The findings reveal that 25 µm Sc3N@C80(OH)18 protects human erythrocytes from radiation‐induced hemolysis. The protective effect is evidenced by reduced release of band 3 protein from radiation‐induced degradation up to 2.115 kGy. The observed effects are proposed to result from ROS scavenging by Sc3N@C80(OH)18 and its bioactivity via membrane protein adsorption. These findings highlight its potential for mitigating radiation‐induced membrane damage, consequently providing a promising foundation for further studies on application in, e.g., cancer therapy.

Intermittent fasting (IF) strategy, including time-restricted eating (TRE), alternate day fasting (ADF), and other variations, is a dietary approach that alternates between periods of eating and fasting. This review investigates the influence of IF on human health, focusing on metabolic effects, cardiometabolic health, neurocognitive functions, and hormonal changes. IF is believed to help in weight reduction, improve insulin sensitivity, and reduce the risk of type II diabetes mellitus. It may also have positive impact on cardiovascular health by reducing blood pressure and improving lipid profiles. Moreover, IF is believed to haveneuroprotective effects, improve cognitive functions and slow the progression ofneurodegenerative diseases. Hormonal changes during IF are very complex and require careful management in conditions like hypothyroidism and Cushing's syndrome. Despite promising results, more research is needed to fully explore the potential negative outcomes and safety of IF. Choice of exact dietary protocol should be individualized and supervised by a healthcare provider.

Tumor microenvironment (TME) has become a major focus of cancer research as a promising therapeutic target. TME comprises cancer cells surrounded by nonmalignant cells, vessels, lymphoid organs, immune cells, nerves, intercellular components, molecules and metabolites located within or near the tumor lesion. Neuromedin U (NMU), a secretory peptide identified in the TME, has gained much attention as an important player in cancer and nonmalignant cell crosstalk. NMU receptors were detected in cancer cells as well as in nonmalignant TME components, such as immune, stromal and endothelial cells. We propose here to discuss the concept that NMU secreted by cancer cells activates cellular components of TME and thus contributes to the formation of microenvironment that favors tumor growth and cancer progression. We summarized the available data on cancer tissues and cell types that have been identified as a source of NMU and/or receptor-expressing NMU targets. We made a critical selection of NMU-receptor positive cell types that are known components of the TME of most malignant tumors. Finally, we discussed whether NMUs and NMU receptors represent a potential therapeutic target for cancer treatment, and summarized information on the tools available to modulate their activity.

AT7519, which inhibits multiple cyclin-dependent kinases, has been extensively investigated in various types of cancer cells. Previous studies have demonstrated the ability of this molecule to suppress the expression of the nuclear receptor retinoic acid-related orphan receptor gamma (RORγ) and several genes involved in hepatocellular carcinoma progression. In this study, we identified a distinct agonistic effect of AT7519 on RORγt, an isoform expressed by various immune cells, including T helper 17 lymphocytes. These immune cells play pivotal roles in shaping the tumor microenvironment and promoting the anticancer response of the immune system. After exposure to AT7519 during differentiation, primary human CD4+ Tcells presented increased expression of IL17A/F, IFNG and GZMB and decreased expression of PDCD1 and CTLA4. These findings elucidate a previously unrecognized facet of AT7519 activity and suggest the potential incorporation of this molecule into immune therapies to augment the effectiveness of diverse anticancer strategies involving anti-programmed cell death protein 1 (anti-PD-1) and anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) regimens.

Reactive oxygen species (ROS) encompass various molecular oxygen derivatives naturally produced during aerobic metabolism, including superoxide anions, hydrogen peroxide, and hydroxyl radicals. Excessive ROS production leads to oxidative distress, causing cellular damage and contributing to various pathologies, often alongside inflammation. Endogenous sources of ROS include mitochondrial activity and NADPH oxidases. The antioxidant system, comprising enzymes such as superoxide dismutase, peroxiredoxin, and catalase, mitigates ROS-induced damage. This review explores the regulation of ROS by membrane receptors, focusing on B1 and B2 kinin receptors and histamine H2 receptors, which are implicated in vasodilation, angiogenesis, inflammation, and gastric acid secretion. Understanding these interactions provides insights into ROS modulation and its role in disease mechanisms.

Cytomegalovirus (CMV) is a pathogen that is common worldwide and is often present in individuals infected with human immunodeficiency virus (HIV). Pattern recognition receptors (PRRs) are host sensors that activate the immune response against infectious agents. However, it is unclear whether PRR single-nucleotide polymorphisms (SNPs) are associated with the occurrence of CMV DNAemia in subjects coinfected with HIV and CMV. HIV/CMV-coinfected patients with and without CMV DNAemia were recruited for this study. The DDX58 rs10813831 and IFIH1 (rs3747517 and rs1990760) polymorphisms were genotyped using the TaqMan Allelic Discrimination Assay, whereas the DDX58 rs12006123 and TLR3 (rs3775291 and rs3775296) SNPs were analyzed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. A mutation present in at least one allele of the DDX58 rs12006123 SNP occurred at least two times more frequently in HIV/CMV-coinfected patients with CMV DNAemia than in coinfected subjects without CMV DNAemia (OR, 2.50; 95% CI, 1.33–4.68; p = 0.004, in the dominant model). A higher level of CMV DNAemia was observed in subjects who had the heterozygous (GA) or homozygous recessive (AA) genotype for the DDX58 rs12006123 SNP compared with those who had the wild-type (GG) genotype (p = 0.0003). Moreover, in subjects with a mutation detected in at least one allele of the DDX58 rs12006123 SNP, a lower serum IFN-β concentration was found compared with those who had a wild-type (GG) genotype for this polymorphism (p = 0.024). The DDX58 rs12006123 SNP is associated with CMV DNAemia in HIV/CMV-coinfected patients.

Human papillomaviruses (HPVs) and herpesviruses are detected in patients with epithelial ovarian cancer (EOC). We sought to analyze the prevalence of HPV’s 16 and 18, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) DNA in peripheral blood, ovarian, and fallopian tube (FT) tissue samples collected from 97 EOC patients, including 71 cases of high-grade serous ovarian carcinoma (HGSOC), and from 60 women with other tumors or non-neoplastic gynecological diseases. DNA isolates were analyzed by PCR methods, including droplet digital PCR. The results demonstrate that (1) HPV16 DNA has been detected in one-third of the FT and tumor samples from EOCs; (2) the prevalence and quantity of HPV16 DNA were significantly higher in FT samples from HGSOCs, non-HGSOCs, and ovarian metastases than in those from non-neoplastic diseases; (3) CMV and EBV have been detected in approximately one-seventh of EOC samples. The results suggest that HPV16 might be a potential risk factor for EOC development.