Mitophagy protects SH-SY5Y neuroblastoma cells against the TNFα-induced inflammatory injury: Involvement of microRNA-145 and Bnip3.

Inflammatory response is involved in the development of facial neuritis. The aim of our study is to explore the role of mitophagy in facial nerve damage induced by tumor necrosis factor α (TNFα). Our results indicated that TNFα induced SH-SY5Y cell apoptosis in a dose-dependent manner. Besides, TNFα treatment also suppressed mitophagy by reducing the expression of BCL2 interacting protein 3 (Bnip3). Overexpression of Bnip3 under sustained SH-SY5Y cell viability in the setting of TNFα-mediated inflammation injury. At the molecular levels, Bnip3 overexpression maintained mitochondrial function via preserving mitochondrial membrane potential, reducing cytochrome-c leakage and inhibiting mitochondrial permeability transition pore opening. Functional studies have suggested that microRNA-145 (miR-145) was an upstream regulator of Bnip3-dependent mitophagy. MiR-145 inhibited Bnip3 transcription and expression, leading to mitophagy inhibition. In contrast, inhibition of miR-145 reversed mitophagy activity and subsequently promoted SH-SY5Y cell survival in the context of TNFα-mediated inflammation injury. Altogether, our data identified Bnip3-dependent mitophagy as one of the defensive mechanisms to sustain mitochondrial homeostasis and SH-SY5Y cell survival. Besides, miR-145/Bnip3/mitophagy axis may be considered as a potential target for the treatment of facial neuritis in clinical practice.

Effect of chitosan combined with hyaluronate on promoting the recovery of postoperative facial nerve regeneration and function in rabbits.

To determine better solutions for postoperative nerve functional recovery, the effects of chitosan and hyaluronate on perineural scar formation and neural function recovery were investigated in 40 rabbits. Rabbits were randomized into 4 groups: A (chitosan), B (chitosan + hyaluronate), C (hyaluronate) and D (control). The rabbits underwent the same parotidectomy surgery, but different materials were used to cover the operated nerves. By evaluating specific indicators, including vibrissae motion tests, neural electrophysiological examinations and extraneural examinations, it was revealed that the amplitude of vibrissae motion of all groups had increased 6 weeks after surgery. The recovery of Group B was superior compared with all other groups at 4 and 12 weeks post-surgery; however no significant differences were detected. Group B exhibited a great number of nerve fibers, thicker myelin sheath and greater nerve conduction velocity. In summary, the use of a chitosan conduit combined with sodium hyaluronate gel may prevent perineural scar formation in facial nerves and promote nerve functional recovery.

Chitosan conduit combined with hyaluronic acid prevent sciatic nerve scar in a rat model of peripheral nerve crush injury.

In the present study, the effects of hyaluronic acid (HA) combined with chitosan conduit on peripheral nerve scarring and regeneration were investigated in a rat model of peripheral nerve crush injury. A total of 60 Sprague-Dawley rats were randomly distributed into four groups (15 rats in each group), in which the nerve was either not treated (control group) or treated with chitosan conduit, hyaluronic acid, or chitosan conduit coupled with hyaluronic acid following clamp injury to the sciatic nerve. The surgical sites were evaluated by assessing the sciatic functional index, the degree of scar adhesions, the numbers of myelinated nerve fibers, the average diameter of myelinated nerve fibers and the myelin sheath thickness. Larger epineurial scar thickness was observed in the control groups compared with the treatment groups at 4, 8 and 12 weeks following surgery. There was no significant difference in scar adhesion among the four groups at 4 weeks following surgery. However, animals receiving chitosan coupled with HA demonstrated better neural recovery, as measured by reduced nerve adherence to surrounding tissues, less scar adhesion, increased number of axons, nerve fiber diameter and myelin thickness. In conclusion, the application of chitosan conduit combined with HA, to a certain extent, inhibited sciatic nerve extraneural scaring and adhesion, and promoted neural regeneration and recovery.

Electron beam melting in the fabrication of three-dimensional mesh titanium mandibular prosthesis scaffold.

The study was designed to fulfill effective work-flow to fabricate three-dimensional mesh titanium scaffold for mandibular reconstruction. The 3D titanium mesh scaffold was designed based on a volunteer with whole mandible defect. (1) acquisition of the CT data; (2) design with computer aided design (CAD) and finite element analysis (FEA). The pore size and intervals with the best mechanic strength was also calculated using FEA. (3) fabrication of the scaffold using electron beam melting (EBM); (4) implantation surgery. The case recovered well, without loosening and rejection. Additionally, 12 mandibular defect model beagles were used to verify the results. The model was established via tooth extraction and mandibular resection surgeries, and the scaffold was designed individually based on CT data obtained at 2 weeks after extraction operation. Then scaffolds were fabricated using 3D EBM, and the implantation surgery was performed at 2 months after extraction operation. All the animals healed well after implantation, and the grafted mandibular recovered well with time. The relevant parameters of the grafted mandibular were nearly to the native mandibular at postoperative 12 months. It is feasible to fabricate mesh titanium scaffold for repairing mandibular defects individually using reverse engineering, CAD and EBM techniques.

[Digital modeling for the individual mandibular 3D mesh scaffold based on 3D printing technology].

OBJECTIVE: To investigate an ideal modeling method of designing 3D mesh scaffold substitutes based on tissue engineering to restore mandibular bone defects. By analyzing the theoretical model from titanium scaffolds fabricated by 3D printing, the feasibility and effectiveness of the proposed methodology were verified. METHODS: Based on the CT scanned data of a subject, the Mimics 15.0 and Geomagic studio 12.0 reverse engineering software were adopted to generate surface model of mandibular bone and the defect area was separated from the 3D model of bone. Then prosthesis was designed via mirror algorithm, in which outer shape was used as the external shape of scaffold. Unigraphics software NX 8.5 was applied on Boolean calculation of subtraction between prosthesis and regular microstructure structure and ANSYS 14.0 software was used to design the inner construction of 3D mesh scaffolds. The topological structure and the geometrical parameters of 3D mesh titanium scaffolds were adjusted according to the aim of optimized structure and maximal strength with minimal weight. The 3D mesh scaffolds solid model through two kinds of computer-aided methods was input into 3D printing equipment to fabricate titanium scaffolds. RESULTS: Individual scaffolds were designed successfully by two modeling methods. The finite element optimization made 10% decrease of the stress peak and volume decrease of 43%, and the porosity increased to 76.32%. This modeling method was validated by 3D printing titanium scaffold to be feasible and effective. CONCLUSIONS: 3D printing technology combined with finite element topology optimization to obtain the ideal mandibular 3D mesh scaffold is feasible and effective.

[RESEARCH ADVANCE OF DIFFERENTIATION OF INDUCED PLURIPOTENT STEM CELLS INTO Schwann CELLS IN VITRO].

OBJECTIVE: To review the research advance of differentiation of induced pluripotent stem cells (iPS) into Schwann cells in vitro in recent years. METHODS: Related literatures on differentiation of iPS into Schwann cells in vitro at present were consulted, the induction methods of iPS differentiating into Schwann cells in vitro were summarized, and the differentiated cells were identified and detected. RESULTS: The research results indicate that iPS can differentiate into Schwann cells. So far, the iPS have to differentiate into neural crest cells or neural crest stem cells firstly, and then differentiate into Schwann cells. S100-ß and glial fibrillary acidic protein (GFAP) are recognized as the marker of Schwann cells. The evidence of generating Schwann cells was that the neural crest cells or neural crest stem cells were labelled by p75+, HNK1+, or nestin+ before differentiation, and by S100-ß⁺ and GFAP⁺ after induction. CONCLUSION: Despite the increasing reported studies of Schwann cells from iPS, there have been few successful induction methods, so this field of cytology needs further study.