Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn(2+) atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes

Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF

Summary: We performed scRNA-seq/snATAC-seq of skeletal muscles post sciatic nerve transection to delineate cell type-specific patterns of gene expression/chromatin accessibility at different time points post-denervation. Unlike myotrauma, denervation selectively activates glial cells and Thy1/CD90-expressing mesenchymal cells. Glial cells expressed Ngf receptor (Ngfr) and were located near neuromuscular junctions (NMJs), close to Thy1/CD90-expressing cells, which provided the main cellular source of NGF post-denervation. Functional communication between these cells was mediated by NGF/NGFR, as either recombinant NGF or co-culture with Thy1/CD90-expressing cells could increase glial cell number ex vivo. Pseudo-time analysis in glial cells revealed an initial bifurcation into processes related to either cellular de-differentiation/commitment to specialized cell types (e.g., Schwann cells), or failure to promote nerve regeneration, leading to extracellular matrix remodeling toward fibrosis. Thus, interactions between denervation-activated Thy1/CD90-expressing and glial cells represent an early abortive process toward NMJs repair, ensued by the conversion of denervated muscles into an environment hostile for NMJ repair

Antibacterial and Antibiofilm Properties of Three Resin-Based Dental Composites against <i>Streptococcus mutans</i>

Antibacterial and antibiofilm properties of restorative dental materials may improve restorative treatment outcomes. The aim of this in vitro study was to evaluate Streptococcus mutans capability to adhere and form biofilm on the surface of three commercially available composite resins (CRs) with different chemical compositions: GrandioSO (VOCO), Venus Diamond (VD), and Clearfil Majesty (ES-2). Disk-shaped specimens were manufactured by light-curing the CRs through two glass slides to maintain a perfectly standardized surface topography. Specimens were subjected to Planktonic OD600nm, Planktonic CFU count, Planktonic MTT, Planktonic live/dead, Adherent Bacteria CFU count, Biomass Quantification OD570nm, Adherent Bacteria MTT, Concanavalin A, and Scanning Electron Microscope analysis. In presence of VOCO, VD, and ES2, both Planktonic CFU count and Planktonic OD600nm were significantly reduced compared to that of control. The amount of Adherent CFUs, biofilm Biomass, metabolic activity, and extracellular polymeric substances were significantly reduced in VOCO, compared to those of ES2 and VD. Results demonstrated that in presence of the same surface properties, chemical composition might significantly influence the in vitro bacterial adhesion/proliferation on resin composites. Additional studies seem necessary to confirm the present results

Multimodal Single Cell profiling of Duchenne Muscular Dystrophy

International audienc

Metabolic Remodeling in Skeletal Muscle Atrophy as a Therapeutic Target

Skeletal muscle is a highly responsive tissue, able to remodel its size and metabolism in response to external demand. Muscle fibers can vary from fast glycolytic to slow oxidative, and their frequency in a specific muscle is tightly regulated by fiber maturation, innervation, or external causes. Atrophic conditions, including aging, amyotrophic lateral sclerosis, and cancer-induced cachexia, differ in the causative factors and molecular signaling leading to muscle wasting; nevertheless, all of these conditions are characterized by metabolic remodeling, which contributes to the pathological progression of muscle atrophy. Here, we discuss how changes in muscle metabolism can be used as a therapeutic target and review the evidence in support of nutritional interventions and/or physical exercise as tools for counteracting muscle wasting in atrophic conditions