73 research outputs found
What is the place of teicoplanin and linezolid in the treatment of prosthetic joint infections?
Recommended from our members
Platelet releasate promotes skeletal myogenesis by increasing muscle stem cell commitment to differentiation and accelerates muscle regeneration following acute injury
Aim: The use of platelets as biomaterials has gained intense research interest. However,
the mechanisms regarding platelet-mediated skeletal myogenesis remain to be established.
The aim of this study was to determine the role of platelet releasate in skeletal myogenesis
and muscle stem cell fate in vitro and ex vivo respectively.
Methods: We analysed the effect of platelet releasate on proliferation and differentiation of
C2C12 myoblasts by means of cell proliferation assays, immunohistochemistry, gene
expression and cell bioenergetics. We expanded in vitro findings on single muscle fibres by
determining the effect of platelet releasate on murine skeletal muscle stem cells using
protein expression profiles for key myogenic regulatory factors.
Results: TRAP6 and collagen used for releasate preparation had a more pronounced effect
on myoblast proliferation versus thrombin and sonicated platelets (P<0.05). In addition,
platelet concentration positively correlated with myoblast proliferation. Platelet releasate
increased myoblast and muscle stem cell proliferation in a dose-dependent manner, which
was mitigated by VEGFR and PDGFR inhibition. Inhibition of VEGFR and PDGFR ablated
MyoD expression on proliferating muscle stem cells, compromising their commitment to
differentiation in muscle fibres (P<0.001). Platelet releasate was detrimental for myoblast
fusion and affected differentiation of myoblasts in a temporal manner. Most importantly we
show that platelet releasate promotes skeletal myogenesis through the PDGF/VEGF-Cyclin
D1-MyoD-Scrib-Myogenin axis and accelerates skeletal muscle regeneration after acute
injury.
Conclusion: This study provides novel mechanistic insights on the role of platelet releasate
in skeletal myogenesis and set the physiological basis for exploiting platelets as biomaterials
in regenerative medicine
The Varicella-Zoster Virus ORF47 Kinase Interferes with Host Innate Immune Response by Inhibiting the Activation of IRF3
The innate immune response constitutes the first line of host defence that limits viral spread and plays an important role in the activation of adaptive immune response. Viral components are recognized by specific host pathogen recognition receptors triggering the activation of IRF3. IRF3, along with NF-κB, is a key regulator of IFN-β expression. Until now, the role of IRF3 in the activation of the innate immune response during Varicella-Zoster Virus (VZV) infection has been poorly studied. In this work, we demonstrated for the first time that VZV rapidly induces an atypical phosphorylation of IRF3 that is inhibitory since it prevents subsequent IRF3 homodimerization and induction of target genes. Using a mutant virus unable to express the viral kinase ORF47p, we demonstrated that (i) IRF3 slower-migrating form disappears; (ii) IRF3 is phosphorylated on serine 396 again and recovers the ability to form homodimers; (iii) amounts of IRF3 target genes such as IFN-β and ISG15 mRNA are greater than in cells infected with the wild-type virus; and (iv) IRF3 physically interacts with ORF47p. These data led us to hypothesize that the viral kinase ORF47p is involved in the atypical phosphorylation of IRF3 during VZV infection, which prevents its homodimerization and subsequent induction of target genes such as IFN-β and ISG15
Pharmacokinetics and use of desferrioxamine in the diagnosis and therapy of aluminium -overload
Farmaceutische kengetallen, farmaceutische verstrekkingen, ambulante praktijk: handleiding
Farmaceutische kengetallen, farmaceutische verstrekkingen, ambulante praktijk: juni 1998
- …