The Yes-associated protein (YAP), one of the major effectors of the Hippo pathway together with its related protein WW-domain-containing transcription regulator 1 (WWTR1; also known as TAZ), mediates a range of cellular processes from proliferation and death to morphogenesis. YAP and WW-domain-containing transcription regulator 1 (WWTR1; also known as TAZ) regulate a large number of target genes, acting as coactivators of DNA-binding transcription factors or as negative regulators of transcription by interacting with the nucleosome remodeling and histone deacetylase complexes. YAP is expressed in self-renewing embryonic stem cells (ESCs), although it is still debated whether it plays any crucial roles in the control of either stemness or differentiation. Here we show that the transient downregulation of YAP in mouse ESCs perturbs cellular homeostasis, leading to the inability to differentiate properly. Bisulfite genomic sequencing revealed that this transient knockdown caused a genome-wide alteration of the DNA methylation remodeling that takes place during the early steps of differentiation, suggesting that the phenotype we observed might be due to the dysregulation of some of the mechanisms involved in regulation of ESC exit from pluripotency. By gene expression analysis, we identified two molecules that could have a role in the altered genome-wide methylation profile: the long noncoding RNA ephemeron, whose rapid upregulation is crucial for the transition of ESCs into epiblast, and the methyltransferase-like protein Dnmt3l, which, during the embryo development, cooperates with Dnmt3a and Dnmt3b to contribute to the de novo DNA methylation that governs early steps of ESC differentiation. These data suggest a new role for YAP in the governance of the epigenetic dynamics of exit from pluripotency.

The Thyroid Hormone (TH) activating enzyme, type 2 Deiodinase (D2), is functionally required to elevate the TH concentration during cancer progression to advanced stages. However, the mechanisms regulating D2 expression in cancer still remain poorly understood. Here, we show that the cell stress sensor and tumor suppressor p53 silences D2 expression, thereby lowering the intracellular THs availability. Conversely, even partial loss of p53 elevates D2/TH resulting in stimulation and increased fitness of tumor cells by boosting a significant transcriptional program leading to modulation of genes involved in DNA damage and repair and redox signaling. In vivo genetic deletion of D2 significantly reduces cancer progression and suggests that targeting THs may represent a general tool reducing invasiveness in p53-mutated neoplasms.

The genus Thymus L., belonging to the Lamiaceae family, contains about 220 species with a distribution that mainly extends in Europe, northwest Africa, Ethiopia, Asia, and southern Greenland. Due to their excellent biological properties, fresh and/or dried leaves and aerial parts of several Thymus ssp. have been utilized in the traditional medicine of many countries. To evaluate not only the chemical aspects but also the biological properties, the essential oils (EOs), obtained from the pre-flowering and flowering aerial parts of Thymus richardii subsp. nitidus (Guss.) Jalas, endemic to Marettimo Island (Sicily, Italy), were investigated. The chemical composition of the EOs, obtained by classical hydrodistillation and GC-MS and GC-FID analyses, showed the occurrence of similar amounts of monoterpene hydrocarbons, oxygenated monoterpenes, and sesquiterpene hydrocarbons. The main constituents of the pre-flowering oil were β-bisabolene (28.54%), p-cymene (24.45%), and thymol methyl ether (15.90%). The EO obtained from the flowering aerial parts showed as principal metabolites β-bisabolene (17.91%), thymol (16.26%), and limonene (15.59%). The EO of the flowering aerial parts, and its main pure constituents, β-bisabolene, thymol, limonene, p-cymene, and thymol methyl ether were investigated for their antimicrobial activity against oral pathogens and for their antibiofilm and antioxidant properties.

LAMA2, coding for the laminin-α2 chain, is a crucial ECM component, particularly abundant in skeletal muscle. Mutations inLAMA2trigger the often-lethalLAMA2-congenital muscular dystrophy (LAMA2-CMD). Various phenotypes have been linked to LAMA2-CMD; nevertheless, the precise mechanisms that malfunction during disease onset in utero remain unknown. We generatedLama2-deficient C2C12 cells and found thatLama2-deficient myoblasts display proliferation, differentiation, and fusion defects, DNA damage, oxidative stress, and mitochondrial dysfunction. Moreover, fetal myoblasts isolated from thedy^Wmouse model of LAMA2-CMD display impaired differentiation and fusion in vitro. We also showed that disease onset during fetal development is characterized by a significant down-regulation of gene expression in muscle fibers, causing pronounced effects on cytoskeletal organization, muscle differentiation, and altered DNA repair and oxidative stress responses. Together, our findings provide unique insights into the critical importance of the laminin-α2 chain for muscle differentiation and muscle cell homeostasis.

The genus Lavandula L., belonging to the Lamiaceae family, contains about forty species with a distribution that mainly extends in the Mediterranean basin from the North Atlantic to the Middle East. Due to their excellent biological properties, the aerial parts and flowers of Lavandula peduncolata ssp. have been utilized in traditional medicine in Morocco and western Europe. This paper investigated the chemical composition and antibacterial activities as well as the antibiofilm and antioxidant activities of the essential oil (EO) obtained from the pre-flowering aerial parts of Lavandula pedunculata subsp. atlantica collected in Morocco. The chemical composition of the EO, obtained by classic hydrodistillation, showed by GC-MS analysis the presence of a large amount of oxygenated monoterpene compounds. The main constituents of the EO were camphor (27.8%), camphene (10.9%), fenchone (10.6%), and eucalyptol (8.5%). The EO has been evaluated for its antimicrobial, antibiofilm, antioxidant and anti-inflammatory properties, showing promising activity against both Gram-positive and Gram-negative strains. These findings highlight the potential of Lavandula EO in combating infections caused by Streptococcus mutans and Streptococcus oralis (oral diseases), Staphylococcus aureus (skin infections), Escherichia coli and Shigella sonnei (gastrointestinal and urinary infections). In addition, although the EO showed no evident effects on cell viability in eukaryotic epithelial cells, it exhibited promising effects on anti-inflammatory properties.

Given the continuous increase in antibiotic resistance, research has been driven towards the isolation of new antimicrobial molecules. Short, charged, and very hydrophobic antimicrobial peptides have a direct action against biological membranes, which are less prone to developing resistance. Using a bioinformatic tool, we chose the SQQ30 peptide, isolated from the human SOGA1 protein. The antimicrobial activity of this peptide against various Gram-negative and Gram-positive bacterial strains and against a fungal strain was studied. A mechanism of action directed against biological membranes was outlined. When administered in combination with the antibiotic ciprofloxacin and with the TRS21 (buforin II), another antimicrobial peptide, SQQ30 can be used with a lower MIC, showing additivity and synergism, respectively. Particularly interesting is the ability of SQQ30 to bind LPS in Gram-negative strains, preventing the eukaryotic cell from releasing inflammatory mediators. Our study indicates SQQ30 as a novel and promising antimicrobial agent.