Ultrasound-Induced Gold Nanoparticle United with Acoustic Reprogramming of Macrophages for Enhanced Cancer Therapy.

Sonodynamic therapy (SDT) has considerable potential in cancer treatment and exhibits high tissue penetration with minimal damage to healthy tissues. The efficiency of SDT is constrained by the complex immunological environment and tumor treatment resistance. Herein, a specific acoustic-actuated tumor-targeted nanomachine is proposed to generate mechanical damage to lysosomes for cancer SDT. The hybrid nanomachine was assembled with gold nanoparticles (GNPs) as the core and encapsulated with macrophage exosomes modified by AS1411 aptamers (GNP@EXO-APs) to optimize the pharmacokinetics and tumor aggregation. GNP@EXO-APs could be specifically transferred to the lysosomes of tumor cells. After induction with ultrasound, GNP@EXO-APs generated strong mechanical stress to produce lysosomal-dependent cell death in cancer cells. Notably, tumor-associated macrophages were reprogrammed in the ultrasound environment to an antitumor phenotype. Enhanced mechanical destruction via GNP@EXO-APs and immunotherapy of cancer cells were verified both in vitro and in vivo under SDT. This study provides a new direction for inside-out killing effects on tumor cells for cancer treatment.

Progress in animal models of trigeminal neuralgia.

OBJECTIVE: This review aims to systematically summarize the methods of establishing various models of trigeminal neuralgia (TN), the scope of application, and current animals used in TN research and the corresponding pain measurements, hoping to provide valuable reference for researchers to select appropriate TN animal models and make contributions to the research of pathophysiology and management of the disease. DESIGN: The related literatures of TN were searched through PubMed database using different combinations of the following terms and keywords including but not limited: animal models, trigeminal neuralgia, orofacial neuropathic pain. To find the maximum number of eligible articles, no filters were used in the search. The references of eligible studies were analyzed and reviewed comprehensively. RESULTS: This study summarized the current animal models of TN, categorized them into the following groups: chemical induction, photochemical induction, surgery and genetic engineering, and introduced various measurement methods to evaluate animal pain behaviors. CONCLUSIONS: Although a variety of methods are used to establish disease models, there is no ideal TN model that can reflect all the characteristics of the disease. Therefore, there is still a need to develop more novel animal models in order to further study the etiology, pathological mechanism and potential treatment of TN.

ALPK1 Expressed in IB4-Positive Neurons of Mice Trigeminal Ganglions Promotes MIA-Induced TMJ pain.

Pain is one of the main reasons for patients with temporomandibular joint (TMJ) disorders seeking medical care. However, there is no effective treatment yet as its mechanism remains unclear. Herein, we found that the injection of monoiodoacetate (MIA) into mice TMJs can induce typical joint pain as early as 3 days, accompanied by an increased percentage of calcitonin gene-related peptide positive (CGRP+) neurons and isolectin B4 positive (IB4+) in the trigeminal ganglions (TGs). Our previous study has discovered that alpha-kinase 1 (ALPK1) may be involved in joint pain. Here, we detected the expression of ALPK1 in neurons of TGs in wild-type (WT) mice, and it was upregulated after intra-TMJ injection of MIA. Meanwhile, the increased percentage of neurons in TGs expressing ALPK1 and CGRP or ALPK1 and IB4 was also demonstrated by the immunofluorescent double staining. Furthermore, after the MIA injection, ALPK1-/- mice exhibited attenuated pain behavior, as well as a remarkably decreased percentage of IB4+ neurons and an unchanged percentage of CGRP+ neurons, as compared with WT mice. In vitro assay showed that the value of calcium intensity was weakened in Dil+ neurons from ALPK1-/- mice of TMJ pain induced by the MIA injection, in relation to those from WT mice, while it was significantly enhanced with the incubation of recombinant human ALPK1 (rhA). Taken together, these results suggest that ALPK1 promotes mice TMJ pain induced by MIA through upregulation of the sensitization of IB4+ neurons in TGs. This study will provide a new potential therapeutic target for the treatment of TMJ pain.

Clinical Application of CAD/CAM-Guided Modified Dautrey's Procedure in Recurrent Temporomandibular Joint Luxation.

This study aimed to introduce the clinical application of the CAD/CAM-guided modified Dautrey's procedure in recurrent anterior temporomandibular joint luxation and evaluate its clinical effects. Four selected patients were treated by the CAD/CAM-guided modified Dautrey's procedure and were followed-up to access their curative effect. Joint pain and sound, recurrence rate, mandibular function, maximum mouth opening (MMO), symptoms of facial nerve injury, and changes in zygomatic facial appearance were observed in postoperative follow-up. The followed-up period ranged from 3 months to 1 year with an average time of 7.5 months. There was no recurrence in all 4 patients, and no symptoms of facial nerve injury and zygomaticofacial appearance changes were found. All patients showed improvement in MMO, with a mean preoperative and postoperative MMO of 4.74 and 3.74 cm, respectively. All of them showed relief of joint pain or sound 3 months or more after the operation and could exercise mandibular normally. This results showed that the CAD/CAM-guided modified Dautrey's procedure was effective in the treatment of recurrent temporomandibular joint luxation and could be used as a good alternative treatment for it.