The disruption of antiviral sensors and the evasion of immune defences by various tactics are hallmarks of EBV infection. One of the EBV latent gene products, LMP1, was shown to induce the activation of signalling pathways, such as NF-κB, MAPK (JNK, ERK1/2, p38), JAK/STAT and PI3K/Akt, via three subdomains of its C-terminal domain, regulating the expression of several cytokines responsible for modulation of the immune response and therefore promoting viral persistence. The aim of this review is to summarise the current knowledge on the EBV-mediated induction of immunomodulatory molecules by the activation of signal transduction pathways with a particular focus on LMP1-mediated mechanisms. A more detailed understanding of the cytokine biology molecular landscape in EBV infections could contribute to the more complete understanding of diseases associated with this virus.

The oxidation of lipids, notably of polyunsaturated fatty acids (PUFAs), under oxidative stress is a self-catalyzed chain reaction that generates reactive aldehydes, among which 4-hydroxynonenal (4-HNE) is considered to act as a second messenger of free radicals. The pleiotropic effects of 4-HNE, which include the regulation of cellular antioxidant capacities, proliferation, differentiation, and apoptosis, are concentration-dependent as they depend on cell type. Therefore, 4-HNE has important roles in various pathophysiological processes and the pathogenesis of acute and chronic diseases, especially degenerative and malignant diseases. Before 4-HNE was recognized as a signaling molecule, it was known to be the cytotoxic mediator of oxidative stress, acting even if lipid peroxidation was not present, because it remains bound to proteins, changing their structure and function. Research in this field has revealed several novel modes of activities of 4-HNE associated with cell death, including not only apoptosis/programmed cell death and necrosis but also ferroptosis, autophagy, pyroptosis, necroptosis, parthanatos, oxeiptosis and cuproptosis. This review shortly summarizes these findings, aiming to encourage further research in the field that might open new ways to use 4-HNE as the bioactive factor for targeted cell death, in particular cancer cells.

A significant portion of the variability in complex features, such as drug response, is likely caused by human genetic diversity. One of the highly polymorphic pharmacogenes is CYP2D6, encoding an enzyme involved in the metabolism of about 25% of commonly prescribed drugs. In a directed search of the 1000 Genomes Phase III variation data, 86 single nucleotide polymorphisms (SNPs) in the CYP2D6 gene were extracted from the genotypes of 2504 individuals from 26 populations, and then used to reconstruct haplotypes. Analyses were performed using Haploview, Phase, and Arlequin softwares. Haplotype and nucleotide diversity were high in all populations, but highest in populations of African ancestry. Pairwise F_ST showed significant results for eleven SNPs, six of which were characteristic of African populations, while four SNPs were most common in East Asian populations. A principal component analysis of CYP2D6 haplotypes showed that African populations form one cluster, Asian populations form another cluster with East and South Asian populations separated, while European populations form the third cluster. Linkage disequilibrium showed that all African populations have three or more haplotype blocks within the CYP2D6 gene, while other world populations have one, except for Chinese Dai and Punjabi in Pakistan populations, which have two.

CYP2D6 is a highly polymorphic gene whose variations affect its enzyme activity. To assess whether the specific population history of Roma, characterized by constant migrations and endogamy, influenced the distribution of alleles and thus phenotypes, the CYP2D6 gene was sequenced using NGS (Next Generation Sequencing) method-targeted sequencing in three groups of Croatian Roma (N = 323) and results were compared to European and Asian populations. Identified single nucleotide polymorphisms (SNPs) were used to reconstruct haplotypes, which were translated into the star-allele nomenclature and later into phenotypes. A total of 43 polymorphic SNPs were identified. The three Roma groups differed significantly in the frequency of alleles of polymorphisms 6769 A > G, 6089 G > A, and 5264 A > G (p < 0.01), as well as in the prevalence of the five most represented star alleles: *1, *2, *4, *10, and *41 (p < 0.0001). Croatian Roma differ from the European and Asian populations in the accumulation of globally rare SNPs (6089 G > A, 4589 C > T, 4622 G > C, 7490 T > C). Our results also show that demographic history influences SNP variations in the Roma population. The three socio-culturally different Roma groups studied differ significantly in the distribution of star alleles, which confirms the importance of a separate study of different Roma groups.

The Roma population suffers from severe poverty, social exclusion, and some of the worst health conditions in the industrialized world. Herein, we report on cardiovascular disease (CVD) risk factors in the Ukrainian Roma and present a meta-analysis of the prevalence of CVD risk factors in 16 Roma populations worldwide. The meta-analyses of CVD risk factors in Roma (n = 16,552) vs. non-Roma majority population of the same country (n = 127,874) included publicly available data. Ukrainian field survey included 339 adults of both sexes and outcomes of interest were hypertension, body mass index (BMI), smoking, education, and employment status. Furthermore, 35.7% of the Ukrainian Roma were hypertensive, 69.3% unemployed, and 48.4% never went to school. Ukrainian Roma women were more likely to be underweight and more prone to be hypertensive, with odds of hypertension increasing with age, BMI, and positive smoking status. Meta-analyses showed that, in comparison with non-Roma worldwide, the Roma bear significantly higher risk factor loads related to smoking (OR = 2.850), diabetes (OR = 1.433), abdominal obesity (OR = 1.276), and metabolic syndrome (OR = 1.975), with lower loads for hypertension (OR = 0.607) and BMI ≥ 25 kg/m² (OR = 0.872). To conclude, the CVD risk factors which are more common in Roma than in the majority population may reflect their poor health-related behaviors and inadequate access to health education.