Gene expression is a complex process that is essential to living organisms. Gene expression plays the important role of converting information that is encoded in a gene into a functional product. The primary regulators of gene expression are transcription factors (TFs). TFs are proteins that can bind specific DNA sequences and regulate gene expression. Their evolution is influenced by a large number of factors, including epigenetic mechanisms, gene regulatory elements and molecular cofactors. These molecular mediators, along with transcription factors, form a network that governs gene expression. Elucidating the mechanisms through which TFs have evolved and how they influence the evolution of other regulatory molecules can provide information on organism evolution and on the development of phenotypic variations. The aim of this review article was to provide a summary of the current literature on transcription factor evolution, function and how such evolution has played an important role in the emergence of complex organisms. Contents

The novel coronavirus SARS-CoV-2 has emerged as a severe threat against public health and global economies. COVID-19, the disease caused by this virus, is highly contagious and has led to an ongoing pandemic. SARS-CoV-2 affects, mainly, the respiratory system, with most severe cases primarily showcasing acute respiratory distress syndrome. Currently, no targeted therapy exists, and since the number of infections and death toll keeps rising, it has become a necessity to study possible therapeutic targets. Antiviral drugs can target various stages of the viral infection, and in the case of SARS-CoV-2, both structural and non-structural proteins have been proposed as potential drug targets. This review focuses on the most researched SARS-CoV-2 proteins, their structure, function, and possible therapeutic approaches.

Studies on extracellular vesicles have increased in recent years. The multi-dimensional nature of their roles in cellular homeostasis, cell-to-cell and tissue-to-tissue communication at the level of the organism, as well as their actions on the holobiome (intra-/interspecies interaction), have garnered the interest of a large number of researchers. Exosomes are one of the most researched classes of extracellular vesicles because they are carriers of targeted protein and DNA/RNA loads. Their multi-functional cargo have been indicated to regulate a vast number of biological pathways in target cells. However, the mechanisms governing these interactions have not yet been fully determined. Endocrinology, by definition, focuses on homeostatic, and cell-to-cell and tissue-to-tissue communication mechanisms. Therefore exosomes should be included in this research topic. Exosomes have previously been associated with a number of endocrine disorders, including obesity, type 2 diabetes mellitus, disorders of the reproductive system and cancer. Furthermore, their biogenesis, composition and function have been associated with viruses, an entirely different domain of life. The profound roles of exosomes in homeostasis, stress and several pathological conditions, in conjunction with their selective and cell-specific composition/function, allude to their use as promising circulating clinical biomarkers of systemic stress and specific pathologic states, and as biocompatible vehicles of therapeutic cargo.The current review provides information on exosomes and discusses their endocrine implications. Contents1. Introduction 2. An in-depth view of exosomes 3. Cell-to-cell interactions and the microenvironment 4. Biological processes 5. Disorders of the endocrine system and exosomes 6. Exosome-based personalized medical applications 7. Conclusion

Nuclear receptors (NRs) are transcriptional factors that play an essential role in all aspects of human development, metabolism and physiology. A prime example of a NR is the glucocorticoid receptor (GR). Structure-wise, the GR is typical of the NR superfamily, while its signaling is a part of multiple physiological mechanisms. In this study, using the GR and the steroid hormone receptors as a basis, an analysis of the structure, function and evolution of the NR ligand binding domain was conducted, while a list of NR mutations was composed in order to examine the effects of the mutations on NR structure and function. The results proposed 7 conserved signaling motifs and identified the amino acid repeating pattern 'LxxLL' or 'LLxxL' in the ligand binding domains (LBDs) of the NRs. Phylogenetic analysis revealed 4 distinct monophyletic branches, and it proposed new evolutionary relations between the LBD of NRs. Furthermore, structural and functional comparisons through NR LBD structures and their corresponding ligands displayed two major canonical forms, one for the steroid hormone-like cluster and another one for the thyroid hormone-like cluster. Last but not least, a new sub-cluster of estrogen receptor α with a specific canonical form has been identified. Although this sub-cluster has 98% similarity in sequence level with all known ERα, shows more significant structural similarity with the ERβ members (RMSD <2Å) rather than the ERα. In particular, the Y537S mutation, which is very common in breast cancer, creates this new transform of ERα'. ERα' is functionally and structurally more similar to ERβ, while still retaining some of its ERα characteristics. This new information may be of high importance in order to understand the signaling mechanisms underlying NRs and cancer.

Alzheimer's disease (AD) is a neurodegenerative disorder that has a significant association with age. Despite its increasing incidence in the population, the etiology of the disease remains poorly understood, and there are currently no effective treatments readily available. The main genes that are associated with AD are the amyloid precursor protein, presenilin-1 and presenilin-2, as well as the apolipoprotein E gene. In addition to genetic factors, a wide range of environmental and lifestyle factors are equally characterized as risk factors for the development of AD, while non-coding RNAs (ncRNAs) and other epigenetic mechanisms play a key role in their detrimental effects. Multiple types of ncRNAs, such as microRNAs, circular RNAs, Piwi-interacting RNAs and long non-coding RNAs are being increasingly implicated in AD. Alterations in ncRNAs can be detected in cerebrospinal fluid, as well in as the brain, highlighting these as promising biomarkers for the detection and treatment of AD. Developments in high-throughput technologies have led to the so-called 'omics' era, which involves the collection of big data and information at both molecular and protein levels, while combining the development of novel computational and statistical tools capable of analyzing and filtering such data. The present review discusses the role of ncRNAs and their use as biomarkers for AD, and summarizes the findings from the application of omics technologies in AD.