Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 has rapidly become a public health emergency of international concern. Although remarkable scientific achievements have been reached since the beginning of the pandemic, the knowledge behind this novel coronavirus, in terms of molecular and pathogenic characteristics and zoonotic potential, is still relatively limited. Today, there is a vaccine, or rather several vaccines, which, for the first time in the history of highly contagious infectious diseases that have plagued mankind, has been manufactured in just one year. Currently, four vaccines are licensed by regulatory agencies, and they use RNA or viral vector technologies. The positive effects of the vaccination campaign are being felt in many parts of the world, but the disappearance of this new infection is still far from being a reality, as it is also threatened by the presence of novel SARS-CoV-2 variants that could undermine the effectiveness of the vaccine, hampering the immunization control efforts. Indeed, the current findings indicate that SARS-CoV-2 is adapting to transmission in humans more efficiently, while further divergence from the initial archetype should be considered. In this review, we aimed to provide a collection of the current knowledge regarding the molecular, phylogenetic, and pathogenetic insights into SARS-CoV-2. The most recent findings obtained with respect to the impact of novel emerging SARS-CoV-2 variants as well as the development and implementation of vaccines are highlighted.

Melanogenesis is the process leading to the synthesis of melanin, the main substance that influences skin color and plays a pivotal role against UV damage. Altered melanogenesis is observed in several pigmentation disorders. Melanogenesis occurs in specialized cells called melanocytes, physically and functionally related by means of autocrine and paracrine interplay to other skin cell types. Several external and internal factors control melanin biosynthesis and operate through different intracellular signaling pathways, which finally leads to the regulation of microphthalmia-associated transcription factor (MITF), the key transcription factor involved in melanogenesis and the expression of the main melanogenic enzymes, including TYR, TYRP-1, and TYRP-2. Epigenetic factors, including microRNAs (miRNAs), are involved in melanogenesis regulation. miRNAs are small, single-stranded, non-coding RNAs, of approximately 22 nucleotides in length, which control cell behavior by regulating gene expression, mainly by binding the 3′ untranslated region (3′-UTR) of target mRNAs. This review collects data on the miRNAs involved in melanogenesis and how these miRNAs can modulate target gene expression. Bringing to light the biological function of miRNAs could lead to a wider understanding of epigenetic melanogenesis regulation and its dysregulation. This knowledge may constitute the basis for developing innovative treatment approaches for pigmentation dysregulation.

Pleural mesothelioma (PM) is a rare and highly aggressive tumor, primarily caused by asbestos exposure. Its long latency period and late-stage diagnosis severely limit therapeutic options. Recent evidence suggests that non-coding RNAs (ncRNAs)-including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)-play key roles in PM biology. This review aims to synthesize current knowledge on ncRNA dysregulation in PM and explore their diagnostic, prognostic, and therapeutic potential. We summarize studies addressing the expression and function of ncRNAs in tumors and in circulating biofluids of PM patients. Particular attention is given to how ncRNAs regulate proliferation, apoptosis, and migration, and how competing endogenous RNA (ceRNA) networks shape gene regulation in PM. Unlike previous reviews, this work integrates findings across different classes of ncRNAs and their interactions, highlighting the emerging concept of ceRNA networks in PM. By bridging molecular mechanisms with potential clinical applications, we provide an updated and comprehensive framework that may inform future strategies for diagnosis, prognosis, and targeted therapy in PM.

The biological activity of retinoic acid or all-trans retinoic acid (ATRA) is mediated by retinoic receptors, which are ligand-dependent transcription factors that activate genes crucial for cell differentiation. Dysregulations of retinoic receptor signaling pathway led to carcinogenesis. A strong in vitro/in vivo antitumor activity of ATRA by modulating the retinoic pathway has been proved in carcinoma of different histotypes. However, the effect of this molecule in Merkel cell carcinoma (MCC), a rare but aggressive skin neoplasm of viral origin in 80% of cases, is unknown. Herein, we investigated the antineoplastic effect of ATRA in Merkel cell polyomavirus (MCPyV)-positive/-negative MCC cells and in human fibroblasts as controls. The antineoplastic effect of ATRA was evaluated at day 3 of treatment by testing MCC cell proliferation, migration, and clonogenicity. Apoptosis/cell death and cell cycle were evaluated via Annexin-V/propidium iodide (P.I.) and TALI assays, respectively. Apoptotic and retinoic pathways were evaluated by RT² Profiler PCR mRNA array, which allows the analysis of pro/anti-apoptotic and retinoic pathway genes (84 + 84 genes), as well as by Western blot (WB) analysis. ATRA treatment led to a strong reduction in MCC cell proliferation, migration and clonogenicity, while inducing cell cycle arrest and promoting apoptosis/death in MCC cells, with a more pronounced effect in MCPyV-positive MCC cells. A significant overexpression of various pro-apoptotic markers in ATRA-treated MCC cells compared to untreated cells was determined by gene expression array and WB analyses. No phenotypic and molecular effects were identified in ATRA-treated fibroblast control cells. Upon ATRA treatments in MCC cells, numerous retinoic signaling genes, such as BMP2, FOXA1, MAFB, RBP4, OLIG2, UCP1 were found to be differentially expressed compared to untreated cells. Our in vitro data indicate that ATRA is effective in reducing MCC cell growth while presenting strong pro-apoptotic effects and favoring cell cycle arrest/death via retinoic receptor signaling pathway regulation.