No abstract

Traumatic brain injury leads to major brain anatomopathological damages underlined by neuroinflammation, oxidative stress and progressive neurodegeneration, ultimately leading to motor and cognitive deterioration. The multiple pathological events resulting from traumatic brain injury can be addressed not by a single therapeutic approach, but rather by a synergistic biotherapy capable of activating a complementary set of signaling pathways and providing synergistic neuroprotective, anti-inflammatory, antioxidative, and neurorestorative activities. Human platelet lysate might fulfill these requirements as it is comprised of a plethora of biomolecules readily accessible as a traumatic brain injury biotherapy. In the present study, we have tested the therapeutic potential of human platelet lysate using in vitro and in vivo models of traumatic brain injury. We first prepared and characterized platelet lysate from clinical-grade human platelet concentrates. Platelets were pelletized, lysed by three freeze-thaw cycles, and centrifuged. The supernatant was purified by 56 °C-30 minutes heat-treatment and spun to obtain the heat-treated platelet pellet lysate that was characterized by ELISA and proteomic analyses. Two mouse models were used to investigate platelet lysate neuroprotective potential. The injury was induced by an in-house manual controlled scratching of the animals' cortex or by controlled cortical impact injury. The platelet lysate treatment was performed by topical application of 60 µL in the lesioned area, followed by daily 60 µL intranasal administration from day 1 to 6 post-injury. Platelet lysate proteomics identified over 1000 proteins including growth factors, neurotrophins, and antioxidants. ELISA detected several neurotrophic and angiogenic factors at ca. 1–50 ng/mL levels. We demonstrate, using the two mouse models of traumatic brain injury that topical application and intranasal platelet lysate consistently improved mice motor function in the beam and rotarod tests, mitigated cortical neuroinflammation, and oxidative stress in the injury area, as revealed by downregulation of pro-inflammatory genes and the reduction in reactive oxygen species levels. Moreover, platelet lysate treatment reduced the loss of cortical synaptic proteins. Unbiased proteomic analyses revealed that HPPL reversed several pathways promoted by both CCI and CBS and related to transport, post-synaptic density, mitochondria or lipid metabolism. The present data strongly support for the first time that human platelet lysate is a reliable and effective therapeutic source of neurorestorative factors. Therefore, brain administration of platelet lysate is a therapeutical strategy that deserves serious and urgent consideration for universal brain trauma treatment.

All the plasma and platelet fractions evaluated in this study exert an anti-inflammatory effect on macrophages, suggesting that both the plasma and platelet proteomes contribute to anti-inflammation. However, the extent and nature of the anti-inflammatory action vary among products. Further studies are needed to better understand the functionality of platelet biomaterials and optimize their clinical use.

Polyetherketoneketone (PEKK) is an alternative material for use in removable partial denture frameworks; these frameworks must exhibit antibacterial properties to reduce the risk of periodontal disease. In the present study, silver nanoparticles (AgNPs) were synthesized via the reduction of silver nitrate with sodium borohydride in a solution containing polyvinyl pyrrolidone (PVP). Transmission electron microscope images and dynamic light scattering confirmed that metallic nanoparticles had been created with an average size of 32 nm. Furthermore, the coating of the PEKK polymeric substrate with 0.5% AgNPs was carried out using an epoxy resin lining at room temperature. Fourier transform infrared (FTIR) spectra confirmed the successful transfer of the AgNP-in-resin lining onto the polymeric substrate. Scanning electron microscopy and atomic force microscopy confirmed that the AgNPs had been uniformly deposited onto the PEKK specimens. Finally, the antibacterial activity of the specimens was tested against Porphyromonas gingivalis. An inhibition zone of 22.5 mm and an antibacterial rate of 83.47% were found for the PEKK coated with 0.5% AgNPs (0.5% Ag-PEKK) compared to an untreated polyetheretherketone (PEEK) substrate, evidencing that 0.5% Ag-PEKK has potential antibacterial properties for implant applications.

Human oral squamous cell carcinoma (OSCC) has been associated with a relatively low survival rate over the years and is characterized by a poor prognosis. C‐X3‐C motif chemokine ligand 1 (CX3CL1) has been involved in advanced migratory cells. Overexpressed CX3CL1 promotes several cellular responses related to cancer metastasis, including cell movement, migration and invasion in tumour cells. However, CX3CL1 controls the migration ability, and its molecular mechanism in OSCC remains unknown. The present study confirmed that CX3CL1 increased cell movement, migration and invasion. The CX3CL1‐induced cell motility is upregulated through intercellular adhesion molecule‐1 (ICAM‐1) expression in OSCC cells. These effects were significantly suppressed when OSCC cells were pre‐treated with CX3CR1 monoclonal antibody (mAb) and small‐interfering RNA (siRNA). The CX3CL1‐CX3CR1 axis activates promoted PLCβ/PKCα/c‐Src phosphorylation. Furthermore, CX3CL1 enhanced activator protein‐1 (AP‐1) activity. The CX3CR1 mAb and PLCβ, PKCα, c‐Src inhibitors reduced CX3CL1‐induced c‐Jun phosphorylation, c‐Jun translocation into the nucleus and c‐Jun binding to the ICAM‐1 promoter. The present results reveal that CX3CL1 induces the migration of OSCC cells by promoting ICAM‐1 expression through the CX3CR1 and the PLCβ/PKCα/c‐Src signal pathway, suggesting that CX3CL1‐CX3CR1‐mediated signalling is correlated with tumour motility and appealed to be a precursor for prognosis in human OSCC.