[Effects of scaffold microstructure and mechanical properties on regeneration of tubular dentin].

Tubular dentin is of great significance in the process of tooth tissue and tooth regeneration, because it is not only the structural feature of primary dentin, but also can affect the tooth sensory function, affect the differentiation of dental pulp cells and provide strong mechanical support for teeth. Scaffold is one of the three elements of tissue engineering dentin regeneration. Most experiments on dentin regeneration involve the study of the microstructure and mechanical properties of the scaffold. The microstructure and mechanical characteristics of scaffold materials have important effects on the differentiation and adhesion of odontoblast, it can directly affect the tissue structure of regenerated dentin.

Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma.

BACKGROUND: Dysregulation of immune checkpoint molecules leads to immune evasion in human tumours but has become a viable target for tumour therapy. Here, we examined expression of Herpes virus entry mediator (HVEM), an immune checkpoint molecule, in human glioblastoma (GBM) to assess its potential as a molecular target for treatment. METHODS: Molecular and clinical data from publicly available genomic databases containing WHO grade II-IV human glioma cases (n = 1866) were analyzed. Immunohistochemistry was applied to assess HVEM protein levels in primary tumour sections. Statistical analysis was performed using Matlab and R language. FINDINGS: HVEM was found to be elevated in aggressive gliomas, particularly in the mesenchymal and isocitrate dehydrogenase (IDH) wild-type molecular subtypes of GBM. HVEMhigh tumours tended to be associated with amplification of EGFR and loss of PTEN, while HVEMlow tumours harbored mutations in IDH1 (93%). HVEM exhibited potential as a prognostic marker based on Cox regression and nomogram models. HVEM displayed intra-tumour heterogeneity and was more highly expressed in peri-necrotic and microvascular regions. Gene ontology and pathway analysis revealed enrichment of HVEM in multiple immune regulatory processes, such as suppression of T cell mediated immunity in GBM. Finally, in cell lineage analysis, HVEM was found to be tightly associated with several infiltrating immune and stromal cell types which localized to the tumour microenvironment. INTERPRETATION: Our data highlights the importance of HVEM in the development of GBM and as a potential molecular target in combination with current immune checkpoint blockades for treatment of GBM.

Effects of human bone morphogenetic protein 2 (hBMP2) on tertiary dentin formation.

Formation of tertiary dentin to maintain pulp vitality is a major odontoblastic response to dental pulp injury. Human bone morphogenetic protein 2 (hBMP2) can promote proliferation and differentiation of odontoblasts. Current study is interested in evaluating if the hBMP2 can promote the regeneration of tertiary dentin and cure dental pulp injury using the adenoviral vector to deliver hBMP2 cDNA into the pulp. Primary culture of dental pulp cells of exfoliated deciduous teeth (hDPCs) was established. Human serotype 5 adenoviral vector, AdCMV-hBMP2, was created. AdCMV-hBMP2 was used to transduce hDPCs in vitro and dental pulp cells in animal model in vivo. Data clearly demonstrated that hBMP2 increased ALP and mineralization. Reverse transcription-real time quantitative PCR (RT-QPCR) data showed that hBMP2 dramatically increased gene expressions of Runx2 (Runt-related transcription factor 2), ALP, Col Iα (Collagen 1a1), SP7 (Osterix), DMP1 (dentin matrix acidic phosphoprotein 1), DSPP (dentin sialophosphoprotein), and BSP (bonesialoprotein), which are normally involved in osteogenesis/odontogenesis. Data from in vivo assays demonstrated that hBMP2 promoted pulp cell proliferation and increased formation of tertiary dentin in dental pulp. Our in vitro and in vivo data suggest that hBMP2 gene can efficiently be delivered into the dental pulp cells by adenovirus, and show potential clinical application for the treatment of dental pulp damage.

TAGLN2 is a candidate prognostic biomarker promoting tumorigenesis in human gliomas.

BACKGROUND: Transgelin-2 (TAGLN2) is a member of the calponin family of actin-bundling proteins that is involved in the regulation of cell morphology, motility, and cell transformation. Here, the clinical significance and potential function of TAGLN2 in malignant gliomas were investigated. METHODS: Molecular and clinical data was obtained from The Cancer Genome Atlas (TCGA) database. Gene ontology and pathway analysis was used to predict potential functions of TAGLN2. RNA knockdown was performed using siRNA or lentiviral contructs in U87MG and U251 glioma cell lines. Cells were characterized in vitro or implanted in vivo to generate orthotopic xenografts in order to assess molecular status, cell proliferation/survival, and invasion by Western blotting, flow cytometry, and 3D tumor spheroid invasion assay, respectively. RESULTS: Increased TAGLN2 expression was associated with increasing tumor grade (P < 0.001), the mesenchymal molecular glioma subtype and worse prognosis in patients (P < 0.001). Immunohistochemistry performed with anti-TAGLN2 on an independent cohort of patients (n = 46) confirmed these results. Gene silencing of TAGLN2 in U87MG and U251 significantly inhibited invasion and tumor growth in vitro and in vivo. Western blot analysis revealed that epithelial-mesenchymal transition (EMT) molecular markers, such as N-cadherin, E-cadherin, and Snail, were regulated in a manner corresponding to suppression of the EMT phenotype in knockdown experiments. Finally, TAGLN2 was induced ~ 2 to 3-fold in U87MG and U251 cells by TGFß2, which was also elevated in GBM and highly correlated with TAGLN2 mRNA levels (P < 0.001). CONCLUSIONS: Our findings indicate that TAGLN2 exerts a role in promoting the development of human glioma. The regulation and function of TAGLN2 therefore renders it as a candidate molecular target for the treatment of GBM.

Development and characterisation of a novel chitosan-coated antioxidant liposome containing both coenzyme Q10 and alpha-lipoic acid.

This article describes the physicochemical properties of chitosan-coated liposomes containing skin-protecting agents, coenzyme Q10 and alpha-lipoic acid (CCAL). CCAL had a spherical shell-core structure and liposomes inverted the surface charge from negative to positive after coating with chitosan. Compared with the uncoated liposome, CCAL had higher zeta potential, larger droplet size and long-term stability. Fourier transform infrared spectroscopy (FTIR) study showed that the driving force for chitosan coating the liposomes was enhanced via hydrogen bonding and ionic bond force between the chitosan and the alpha-lipoic acid. While the encapsulation efficiency (EE) of alpha-lipoic acid also increased by interacting with the chitosan shell. In vitro antioxidant activity study showed an excellent hydroxyl radical scavenging activity of CCAL. In vitro release study displayed a sustained drug release, and in vitro penetration studies promoted the accumulation of drugs in rabbit skin.

Preoperative demonstration of neurovascular relationship in trigeminal neuralgia by using 3D FIESTA sequence.

PURPOSE: The purpose of the study was to evaluate the value of high-resolution three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) imaging in the visualization of neurovascular relationship in patients with trigeminal neuralgia (TN). METHODS: Thirty-seven patients with unilateral typical TN underwent 3D FIESTA imaging. Neurovascular relationship at the trigeminal root entry zone was reviewed by an experienced neuroradiologist, who was blinded to the clinical details. The imaging results were compared with the operative findings in all patients. RESULTS: In 37 patients with TN, 3D FIESTA imaging identified surgically verified neurovascular contact in 35 of 36 symptomatic nerves. Based on surgical findings, the sensitivity and specificity of magnetic resonance (MR) imaging were 97.2% and 100%, respectively. Agreement between the position (medial, lateral, superior and inferior) of the compressing vessel relative to the trigeminal nerve identified by MR imaging and surgery was excellent (K=0.81; 95% confidence interval, 0.56-1.00). A statistically significant difference was found between the site of neurovascular contact and the clinical symptom related to the trigeminal branch (Fisher's Exact Test, P<.001). CONCLUSIONS: Use of 3D FIESTA sequence enables accurate visualization of neurovascular contact in patients with TN. Anatomic relationships defined by this method can be useful in surgical planning and predicting surgical findings.

[Preoperative enhanced three-dimensional spoiled gradient-recalled imaging for microvascular decompression of trigeminal neuralgia].

OBJECTIVE: To study the preoperative high resolution three-dimensional MR imaging of idiopathic trigeminal neuralgia, demonstrating the use in selection of patients and planning of the treatment. METHODS: The enhanced three-dimensional spoiled gradient-recalled imaging and three-dimensional MR angiography with 3-T MRI system were used to detect the anatomic relationship of neural and vascular structures at the trigeminal root entry zone preoperatively, surgical findings served as a reference to compare the MR visualization with the exact anatomic relations. RESULTS: Twenty-nine of 33 patients, who had the MRI positive vascular contact or compression, which was consistent to the symptom side, received the microvascular decompression (MVD). Surgical findings revealed neurovascular conflicts in all subjects, 27 of 29 (93%) were consistent to the imaging results, all the patients treated with MVD had the immediate complete pain relief. CONCLUSIONS: High-resolution MR imaging successfully demonstrated its usefulness in detecting the neurovascular contact at the trigeminal root entry zone, thereby facilitating the selection of patients who were most likely to benefit from MVD.