Staff member

The invasion of human embryos in the uterus overcoming the maternal tissue barrier is a crucial step in embryo implantation and subsequent development. Although tissue invasion is fundamentally a mechanical process, most studies have focused on the biochemical and genetic aspects of implantation. Here, we fill the gap by using a deformable ex vivo platform to visualize traction during human embryo implantation. We demonstrate that embryos apply forces remodeling the matrix with species-specific displacement amplitudes and distinct radial patterns: principal displacement directions for mouse embryos, expanding on the surface while human embryos insert in the matrix generating multiple traction foci. Implantation-impaired human embryos showed reduced displacement, as well as mouse embryos with inhibited integrin-mediated force transmission. External mechanical cues induced a mechanosensitive response, human embryos recruited myosin, and directed cell protrusions, while mouse embryos oriented their implantation or body axis toward the external cue. These findings underscore the role of mechanical forces in driving species-specific invasion patterns during embryo implantation.

JTD Keywords: Animals, Anterior-posterior axis, Biomechanical phenomena, Cells, Collagen, Differentiatio, Embryo implantation, Embryo, mammalian, Female, Humans, Mechanotransduction, cellular, Mice, Morphogenesis, Pregnancy, Range, Self-organization, Species specificity, Trophoblast invasion, Uterine contractions

Oleanolic acid (OA) and maslinic acid (MA) are pentacyclic triterpenic compounds that abound in industrial olive oil waste. These compounds have renowned antimicrobial properties and lack cytotoxicity in eukaryotic cells as well as resistance mechanisms in bacteria. Despite these advantages, their antimicrobial activity has only been tested in vitro, and derivatives improving this activity have not been reported. In this work, a set of 14 OA and MA C-28 amide derivatives have been synthesized. Two of these derivatives, MA-HDA and OA-HDA, increase the in vitro antimicrobial activity of the parent compounds while reducing their toxicity in most of the Gram-positive bacteria tested, including a methicillin-resistant Staphylococcus aureus-MRSA. MA-HDA also shows an enhanced in vivo efficacy in a Galleria mellonella invertebrate animal model of infection. A preliminary attempt to elucidate their mechanism of action revealed that these compounds are able to penetrate and damage the bacterial cell membrane. More significantly, their capacity to reduce antibiofilm formation in catheters has also been demonstrated in two sets of conditions: a static and a more challenged continuous-flow S. aureus biofilm.

JTD Keywords: Antibiofilm, Galleria mellonella, In vitro and in vivo antimicrobials, Maslinic and oleanolic acids, Natural products, Staphylococcus aureus