Localization of Magic-F1 Transgene, Involved in Muscular Hypertrophy, during Early Myogenesis

We recently showed that Magic-F1 (Met-activating genetically improved chimeric factor 1), a human recombinant protein derived from hepatocyte growth factor/scatter factor (HGF/SF) induces muscle cell hypertrophy but not progenitor cell proliferation, both in vitro and in vivo. Here, we examined the temporal and spatial expression pattern of Magic-F1 in comparison with Pax3 (paired box gene 3) transcription factor during embryogenesis. Ranging from 9.5 to 17.5 dpc (days post coitum) mouse embryos were analyzed by in situ hybridization using whole mounts during early stages of development (9.5–10.5–11.5 dpc) and cryostat sections for later stages (11.5–13.5–15.5–17.5 dpc). We found that Magic-F1 is expressed in developing organs and tissues of mesenchymal origin, where Pax3 signal appears to be downregulated respect to the wt embryos. These data suggest that Magic-F1 could be responsible of muscular hypertrophy, cooperating with Pax3 signal pathway in skeletal muscle precursor cells

Guide cells support muscle regeneration and affect neuro-muscular junction organization

Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them 'guide' cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the forming myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regeneration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers

Magic-F1 transgene cooperates with Pax 3 during early myogenesis to induce muscular hypertrophy

Met-Activating Genetically Improved Chimeric Factor-1 (Magic-F1) is a human recombinant protein derived from hepatocyte growth factor/scatter factor (HGF/ SF) and consists in two Met-binding domains repeated in tandem and separated by an artificial linker. It has a reduced affinity for Met and, in contrast to HGF, it elicits activation of the AKT but not the ERK signaling pathway. We recently showed that Magic-F1 induces muscle cell hypertrophy but not progenitor cell proliferation, both in vitro and in vivo where a transgenic mouse express the recombinant protein exclusively in skeletal muscle tissue [1]. Here, we examined the temporal and spatial expression pattern of Magic-F1 in comparison with Pax3 (paired box gene 3) transcription factor during embryogenesis [2]. Ranging from 9.5 to 17.5 dpc (days post coitum) mouse embryos were analyzed by in situ hybridization using whole mounts during early stages of development (9.5-10.5-11.5 dpc) and cryostat sections for later stages (11.5-13.5-15.5-17.5 dpc). We found that Magic-F1 is expressed in developing organs and tissues of mesenchymal origin, where Pax3 signal appears to be downregulated respect to the wt embryos. These data suggest that Magic-F1 could be responsible of muscular hypertrophy, cooperating with Pax3 signal pathway in skeletal muscle precursor cells

Localization of Magic-F1 Transgene, Involved in Muscular Hypertrophy, during Early Myogenesis

We recently showed that Magic-F1 (Met-activating genetically improved chimeric factor 1), a human recombinant protein derived from hepatocyte growth factor/scatter factor (HGF/SF) induces muscle cell hypertrophy but not progenitor cell proliferation, both in vitro and in vivo. Here, we examined the temporal and spatial expression pattern of Magic-F1 in comparison with Pax3 (paired box gene 3) transcription factor during embryogenesis. Ranging from 9.5 to 17.5 dpc (days post coitum) mouse embryos were analyzed by in situ hybridization using whole mounts during early stages of development (9.5-10.5-11.5 dpc) and cryostat sections for later stages (11.5-13.5-15.5-17.5 dpc). We found that Magic-F1 is expressed in developing organs and tissues of mesenchymal origin, where Pax3 signal appears to be downregulated respect to the wt embryos. These data suggest that Magic-F1 could be responsible of muscular hypertrophy, cooperating with Pax3 signal pathway in skeletal muscle precursor cells

miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitors

miR669a and miR669q inhibit postnatal cardiac progenitor differentiation by directly targeting the 3′UTR of MyoD

Association of Neuroretinal Thinning and Microvascular Changes with Hypertension in an Older Population in Southern Italy.

Retinal microvasculature assessment at capillary level may potentially aid the evaluation of early microvascular changes due to hypertension. We aimed to investigate associations between the measures obtained using optical coherence tomography (OCT) and OCT-angiography (OCT-A) and hypertension, in a southern Italian older population. We performed a cross-sectional analysis from a population-based study on 731 participants aged 65 years+ subdivided into two groups according to the presence or absence of blood hypertension without hypertensive retinopathy. The average thickness of the ganglion cell complex (GCC) and the retinal nerve fiber layer (RNFL) were measured. The foveal avascular zone area, vascular density (VD) at the macular site and of the optic nerve head (ONH) and radial peripapillary capillary (RPC) plexi were evaluated. Logistic regression was applied to assess the association of ocular measurements with hypertension. GCC thickness was inversely associated with hypertension (odds ratio (OR): 0.98, 95% confidence interval (CI): 0.97-1). A rarefaction of VD of the ONH plexus at the inferior temporal sector (OR: 0.95, 95% CI: 0.91-0.99) and, conversely, a higher VD of the ONH and RPC plexi inside optic disc (OR: 1.07, 95% CI: 1.04-1.10; OR: 1.04, 95% CI: 1.02-1.06, respectively) were significantly associated with hypertension. A neuroretinal thinning involving GCC and a change in capillary density at the peripapillary network were related to the hypertension in older patients without hypertensive retinopathy. Assessing peripapillary retinal microvasculature using OCT-A may be a useful non-invasive approach to detect early microvascular changes due to hypertension

Scedosporium apiospermum contact lens-related keratitis: A rare case report and a literature review

Background: Scedosporium apiospermum (SA) is commonly present in temperate climates. It can induce cutaneous and subcutaneous tissue infections as well as disseminated infections in immunocompromised or immunocompetent hosts. The eye is rarely involved. Keratomycosis is usually caused by plant-related injuries. Here, we describe a patient with a severe and sight-threatening corneal abscess caused by SA, which was associated with contact lens wear and was successfully treated with a combination of surgical and medical therapies. Case Presentation: An otherwise healthy 22-year-old woman, with history of contact lens wearing, was referred to the Ophthalmic Department of Bari University, Bari, Italy for evaluation of a corneal abscess and hypopyon in her left eye. Intensive topical and systemic antibiotic therapy was initiated after obtaining conjunctival swabs. Within 2 days, her ophthalmic condition had worsened, and her best-corrected visual acuity (BCVA) dropped to counting fingers. She underwent penetrating keratoplasty, after which her ophthalmic condition improved. Microbiological culture, obtained from the explanted cornea, revealed SA infection. This was addressed with specific topical and systemic therapy using voriconazole. Two weeks later, the condition of her left eye was stable, with mild corneal edema and no sign of acute graft rejection. Her BCVA improved to 20/25, and all medications were discontinued, except for the steroid eye drop. The patient was scheduled for a 1-month follow-up. Conclusions: Prompt identification of the etiological agent is mandatory to perform appropriate therapy in cases of keratomycosis. Surgery to remove the infected cornea is helpful in patients with deteriorating condition, in whom the initial medical therapy has failed. Topical and systemic antimycotic therapy, based on microbiological culture, is recommended as an adjunctive therapy for the surgical management of severe corneal mycotic abscesses