Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis

Uraemic toxins increase in serum parallel to a decline in the glomerular filtration rate and the development of sarcopenia in patients with chronic kidney disease (CKD). This study analyses the role of uraemic toxins in sarcopenia at different stages of CKD, evaluating changes in the muscular regeneration process. Cultured C2C12 cells were incubated with a combination of indoxyl sulphate and p-cresol at high doses (100 µg/mL) or low doses (25 µg/mL and 10 µg/mL) resembling late or early CKD stages, respectively. Cell proliferation (analysed by scratch assays and flow cytometry) was inhibited only by high doses of uraemic toxins, which inactivated the cdc2-cyclin B complex, inhibiting mitosis and inducing apoptosis (analysed by annexin V staining). By contrast, low doses of uraemic toxins did not affect proliferation, but reduced myogenic differentiation, primed with 2% horse serum, by inhibiting myogenin expression and promoting fibro-adipogenic differentiation. Finally, to assess the in vivo relevance of these results, studies were performed in gastrocnemii from uraemic rats, which showed higher collagen expression and lower myosin heavy chain expression than those from healthy rats. In conclusion, uraemic toxins impair the skeletal muscular regeneration process, even at low concentrations, suggesting that sarcopenia can progress from the early stages of CKD.

Primate heart regeneration via migration and fibroblast repulsion by human heart progenitors

SUMMARYHuman heart regeneration is one of the most critical unmet clinical needs at a global level1. Muscular regeneration is hampered both by the limited renewing capacity of adult cardiomyocytes2-4 and the onset of cardiac fibrosis5,6, resulting in reduced compliance of the tissue. Primate have proven to be ideal models for pluripotent stem cell strategies for heart regeneration, but unravelling specific approaches to drive cell migration to the site of injury and inhibition of subsequent fibrosis have been elusive. Herein, by combining human cardiac progenitor lineage tracing and single-cell transcriptomics in injured non-human primate heart bio-mimics, we uncover the coordinated muscular regeneration of the primate heart via directed migration of human ventricular progenitors to sites of injury, subsequent fibroblast repulsion targeting fibrosis, and ultimate functional replacement of damaged cardiac muscle by differentiation and electromechanical integration. Single-cell RNAseq captured distinct modes of action, uncovering chemoattraction mediated by CXCL12/CXCR4 signalling and fibroblast repulsion regulated by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Moreover, transplantation of human cardiac progenitors into hypo-immunogenic CAG-LEA29Y transgenic porcine hearts following injury proved their chemotactic response and their ability to generate a remuscularized scar without the risk of arrhythmogenesis in vivo. Our study demonstrates that inherent developmental programs within cardiac progenitors are sequentially activated in the context of disease, allowing the cells to sense and counteract injury. As such, they may represent an ideal bio-therapeutic for functional heart rejuvenation.

Calcification of Axial Skeleton and Segmentation Muscular Regeneration of Gecko’s Tail (Gekko Gecko Linnaeus, 1758)

Gecko is an animal that can carry out autotomy. Research on gecko tail autotomy has been carried out, but there are still few who research the axial skeleton that focuses on vertebrae caudales and segmentation muscular arranged, this is the background of this research. This research is expected to be data base further research and as a comparison between animals that can induce further autotomy. This study aims to determine the macrostructure and microstructure of axial axial gecko tail regenerates and determine the anatomical microstructure of muscular regeneration of gecko tail. The methods used were X-Ray, Alizarin Red S and Alcian Blue, Paraffin method with hematoxylin-eosin staining, and Mallory Triple Stain. The results showed that the color of the gecko tail regenerate was paler compared to the original tail. On observations using radiological rays and alizarin staining showed that the original tail wo uld look segmented and have a process. The original gecko tail is composed of bones, because it is red which shows perfectly calcified bone. While the gecko tail regenerate is composed of cartilage that is shaped like a long pipe glazed red because it has calcified. At the end of the tail there is also a blue color, this indicates that the gecko tail regenerate has not been completely calcified. Segmentation Muscular of the original gecko tail, when viewed longitudinally, indicates a segment that extends from one process to the skin and when viewed from the cross has only four muscle segments separated by the septum. While the gecko tail regenerate when viewed in a longitudinal manner there is no segment and when seen transversely there are 12 muscle segments seen. Muscles are composed of a collection of myotubes that form myotomes, each myotomes limited by myoseptum.

Η χρήση μεβράνης κολλαγόνου ίππειου περικάρδιου για την αποκατάσταση ελλειμάτων στομάχου

Objective The objective of this study was to test the efficacy of an equine pericardial patch forthe repair of full-thickness defects of the stomach wall.Materials and methods Circular defects of 1.5 cm diameter, on the anterior wall of thestomach of 12 female New Zealand rabbits, were repaired by an equine pericardial patch.After euthanasia at six different time intervals (3 days- 8 weeks) macroscopic evaluation of theabdominal cavity (including adhesion scoring), mechanical testing and histologicalexamination of the stomach were performed.Results All animals survived the operative procedure and had a normal post-operative course,without complications, until euthanasia. None of the patches failed and the abdomen remainedgrossly intact in all cases. Adhesions were observed in all animals and were quite significant in3/12 animals. Bursting pressure testing indicated that the repair was durable and that adequatestrength to prevent local failure was achieved by the second week. Histological examinationshowed gradual narrowing of the perforation site by mucosal and limited muscular regeneration. By the end of the observation period, a well-organized, vascularized, andstructured fibrotic layer had formed on the outside of the patch, which was undergoing slowdegradation.Conclusions The equine pericardial patch was successfully used to repair a gastric defect inour experimental model and it seems that it could have potential as a material suitable forfurther research, concerning repair of upper gastrointestinal defects.