METTL3 promotes immature dental pulp stem cells-induced angiogenesis by regulating ETS1 mRNA stability in an m6A-HuR-dependent manner.

Angiogenesis serves as the determinate element of pulp regeneration. Dental pulp stem cell (DPSC) implantation can promote the regeneration of dental pulp tissue. Herein, the role of m6A methyltransferase methyltransferase-like 3 (METTL3) in regulating DPSCs-induced angiogenesis during pulp regeneration therapy was investigated. Cell DPSC viability, HUVEC migration, and angiogenesis ability were analyzed by CCK-8 assay, wound healing, Transwell assay, and tube formation assay. The global and EST1 mRNA m6A levels were detected by m6A dot blot and Me-RIP. The interactions between E26 transformation-specific proto-oncogene 1(ETS1), human antigen R(HuR), and METTL3 were analyzed by RIP assay. The relationship between METTL3 and the m6A site of ETS1 was performed by dual-luciferase reporter assay. ETS1 mRNA stability was examined with actinomycin D. Herein, our results revealed that human immature DPSCs (hIDPSCs) showed stronger ability to induce angiogenesis than human mature DPSCs (hMDPSCs), which might be related to ETS1 upregulation. ETS1 knockdown inhibited DPSCs-induced angiogenesis. Our mechanistic experiments demonstrated that METTL3 increased ETS1 mRNA stability and expression level on DPSCs in an m6A-HuR-dependent manner. ETS1 upregulation abolished sh-METTL3's inhibition on DPSCs-induced angiogenesis. METTL3 upregulation promoted DPSCs-induced angiogenesis by enhancing ETS1 mRNA stability in an m6A-HuR-dependent manner. This study reveals a new mechanism by which m6A methylation regulates angiogenesis in DPSCs, providing new insights for stem cell-based tissue engineering.

Multi-shell structured fluorescent-magnetic nanoprobe for target cell imaging and on-chip sorting.

In this paper, we have developed a core-triple-shell structured multi-functional nanoprobe Fe3O4/SiO2/CdSeTe@ZnS-SiO2/polydopamine with strong fluorescence and a fast magnetic response for specifically recognizing, fluorescently labeling, and magnetically sorting target tumor cells on a microfluidic chip. The outer polydopamine layer not only effectively alleviated the quenching effect of the interlayer quantum dots but also provided a convenient and versatile functional interface to readily conjugate with the recognizing model molecules of aptamer KH1C12 with amine, thiol, or carboxyl groups. Moreover, the polydopamine isolation and PEG decoration equipped the as-fabricated nanoprobes with little cytotoxicity and nonspecific affinity, leading to the effective and specific profiling of the protein epitopes expressed on the target tumor cells. Taking advantage of the magnetic property and specific recognition, the modified nanoprobe was utilized to label and isolate HL-60 cells from a homogeneous cell mixture of HL-60 and K562 cells on a microfluidic chip. Combining with the high throughput of the microfluidic chip, 1.0 × 10(4) HL-60 cells were readily separated from 2.0 × 10(4) cells in only 10 min with 98% separation efficiency, markedly improved in comparison with conventional strategies. This study presents an innovative strategy for developing highly integrated nanoprobes of strong fluorescence and magnetic controllability, opening up a promising probe-based avenue for biological imaging and separation.

Anesthetic efficacy of inferior alveolar nerve block plus buccal infiltration or periodontal ligament injections with articaine in patients with irreversible pulpitis in the mandibular first molar.

OBJECTIVE: We compared the anesthetic efficacy of inferior alveolar nerve block (IANB) plus buccal infiltration (BI) and IANB plus periodontal ligament (PDL) articaine injections in patients with irreversible pulpitis in the mandibular first molar. STUDY DESIGN: Fifty-seven volunteers, patients with irreversible pulpitis in the mandibular first molar admitted to the Department of Stomatology, Second Affiliated Hospital, Sun Yat-Sen University, randomly received conventional IANB, containing 1.7 mL 4% articaine/HCl with 1:100,000 epinephrine, plus either BI or PDL injections containing 0.4 mL articaine/HCl with 1:100,000 epinephrine. The patients recorded the pain of the injections and endodontic access on a Heft-Parker visual analog scale (VAS). RESULTS: According to the VAS scores, all patients experienced no or mild pain with BI and PDL injections after the application of IANB. Anesthetic success occurred in 81.48% for IANB plus BI (IANB/BI) compared with 83.33% for IANB plus PDL injection (IANB/PDL injection). None of the observed differences between the 2 groups was significant (P > .05). CONCLUSION: Both injection combinations resulted in high anesthetic success in patients with irreversible pulpitis in the mandibular first molar.

[The study on characteristics of soft tissue profile for different malocclusion].

OBJECTIVE: To study the coordination of facial soft tissue in Angle's Class I, II1, III malocclusion, providing reference for the clinical practice. METHODS: 60 lateral cephalometric radiographs of three classes of Angle's malocclusion were included. 13 measurements were analyzed by SPSS 10.0. RESULTS: Protrusion of the upper and lower lips increased in Angle's II1 comparing with Angle's I and protrusion of the upper lip was larger than the lower lip, no difference was found in the facial convexity. Increase of upper lip inclination and underdevelopment of maxillary in Angle's III comparing with Angle's I. No significant different was found in the form of lower lip, soft tissue facial angle and Z angle. Comparing Angle's II1 with Angle's III, every measurements were significantly different except upper lip inclination, nasolabial angle, representing the formation mechanism of malocclusion. CONCLUSION: Some differences were found in form and position of lip in three classes of Angle's malocclusion. However, the deformity was not obvious in Angle's II1 and Angle's III because of compensation mechanism. Nasolabial angle only reflected change of upper lip, but could not reflect characters of facial profile.