Tween-20-Modified BiVO4 Nanorods for CT Imaging-Guided Radiotherapy of Tumor.

Oral cancer is the most common malignant tumor in the oral and maxillofacial region, which seriously threatens the health of patients. At present, radiotherapy is one of the commonly used methods for oral cancer treatment. However, the resistance of cancerous tissues to ionizing radiation, as well as the side effects of X-rays on healthy tissues, still limit the application of radiotherapy. Therefore, how to effectively solve the above problems is still a challenge at present. Generally speaking, elements with high atomic numbers, such as bismuth, tungsten, and iodine, have a high X-ray attenuation capacity. Using nanomaterials containing these elements as radiosensitizers can greatly improve the radiotherapy effect. At the same time, the modification of nanomaterials based on the above elements with the biocompatible polymer can effectively reduce the side effects of radiosensitizers, providing a new method for the realization of efficient and safe radiotherapy for oral cancer. In this work, we prepared Tween-20-modified BiVO4 nanorods (Tw20-BiVO4 NRs) and further used them in the radiotherapy of human tongue squamous cell carcinoma. Tw20-BiVO4 NRs are promising radiosensitizers, which can generate a large number of free radicals under X-rays, leading to the damage of cancer cells and thus playing a role in tumor therapy. In cell experiments, radiotherapy sensitization of Tw20-BiVO4 NRs significantly enhanced the production of free radicals in oral cancer cells, aggravated the destruction of chromosomes, and improved the therapeutic effect of radiotherapy. In animal experiments, the strong X-ray absorption ability of Tw20-BiVO4 NRs makes them effective contrast agents in computed tomography (CT) imaging. After the tumors are located by CT imaging, it helps to apply precise radiotherapy; the growth of subcutaneous tumors in nude mice was significantly inhibited, confirming the remarkable effect of CT imaging-guided radiotherapy.

PEEK for Oral Applications: Recent Advances in Mechanical and Adhesive Properties.

Polyetheretherketone (PEEK) is a thermoplastic material widely used in engineering applications due to its good biomechanical properties and high temperature stability. Compared to traditional metal and ceramic dental materials, PEEK dental implants exhibit less stress shielding, thus better matching the mechanical properties of bone. As a promising medical material, PEEK can be used as implant abutments, removable and fixed prostheses, and maxillofacial prostheses. It can be blended with materials such as fibers and ceramics to improve its mechanical strength for better clinical dental applications. Compared to conventional pressed and CAD/CAM milling fabrication, 3D-printed PEEK exhibits excellent flexural and tensile strength and parameters such as printing temperature and speed can affect its mechanical properties. However, the bioinert nature of PEEK can make adhesive bonding difficult. The bond strength can be improved by roughening or introducing functional groups on the PEEK surface by sandblasting, acid etching, plasma treatment, laser treatment, and adhesive systems. This paper provides a comprehensive overview of the research progress on the mechanical properties of PEEK for dental applications in the context of specific applications, composites, and their preparation processes. In addition, the research on the adhesive properties of PEEK over the past few years is highlighted. Thus, this review aims to build a conceptual and practical toolkit for the study of the mechanical and adhesive properties of PEEK materials. More importantly, it provides a rationale and a general new basis for the application of PEEK in the dental field.

PVP-Modified Multifunctional Bi2WO6 Nanosheets for Enhanced CT Imaging and Cancer Radiotherapy.

Malignant tumors are one of the main causes of human death. The clinical treatment of malignant tumors is usually surgery, chemotherapy, radiotherapy, and so forth. Radiotherapy, as a traditional and effective treatment method for cancer, is widely used in clinical practice, but the radiation resistance of tumor cells and the toxic side effects to normal cells are still the Achilles heel of radiotherapy. Multifunctional inorganic high-atom nanomaterials are expected to enhance the effect of tumor radiotherapy. Tungsten and bismuth, which contain elements with high atomic coefficients, have strong X-ray energy attenuation capability. We synthesized Bi2WO6 nanosheets (NSs) using a hydrothermal synthesis method and modified polyvinylpyrrolidone (PVP) on their surface to make them more stable. PVP-Bi2WO6 NSs have a variety of effects after absorbing X-rays (such as the photoelectric effect and Compton effect) and release a variety of particles such as photoelectrons, Compton electrons, auger electrons, and so forth, which can react with organic molecules or water in cells, generate a large number of free radicals, and promote cell apoptosis, thereby improving the effect of radiotherapy. We show through γ-H2AX and DCFH-DA probe analysis experiments that PVP-Bi2WO6 NSs can effectively increase cell DNA damage and reactive oxygen species formation under X-ray irradiation. Clone formation analysis showed that PVP-Bi2WO6 NSs can effectively suppress cell colony formation under X-ray irradiation. These versatile functions endow PVP-Bi2WO6 NSs with enhanced radiotherapy efficacy in animal models. In addition, PVP-Bi2WO6 NSs can also be used as contrast agents for X-ray computed tomography (CT) imaging with obvious effects. Therefore, PVP-Bi2WO6 NSs can be used as CT imaging contrast agents and tumor radiotherapy sensitizers and have potential medical applications.

Long non­coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR­21/PTEN/Akt axis.

Radioresistance hinders the therapeutic outcomes of radiotherapy in non­small cell lung cancer (NSCLC). Although long non­coding RNAs (lncRNAs) have been demonstrated to participate in the regulation of multiple cell behaviors, whether they can modulate the radiosensitivity of NSCLC and the underlying molecular mechanisms have not been well investigated. In the present study, it was revealed that NSCLC NCI­H460 cells were more sensitive to ionizing radiation (IR) than A549 cells. Using the RNA­Seq method, four highly differentially expressed lncRNAs were identified, including the growth arrest­specific transcript 5 (GAS5), syntaxin binding protein 5 antisense RNA 1 (STXBP5­AS1), metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and X­inactive specific transcript (XIST), which were predicted to play roles in the acquisition of radiosensitivity. Using real­time quantitative PCR (qPCR), it was demonstrated that lncRNA GAS5 was significantly upregulated in NCI­H460 cells but not in A549 cells during IR. Mechanistically, it was demonstrated that overexpression of lncRNA GAS5 decreased the level of microRNA­21 (miR­21). Overexpression of lncRNA GAS5 or suppression of miR­21 markedly increased the IR­induced cell apoptosis of A549 cells. It was also demonstrated that overexpression of lncRNA GAS5 increased PTEN expression and suppressed Akt phosphorylation through the modulation of miR­21. Notably, it was revealed that IR enhanced the interaction between lncRNA GAS5 and the miR­21/PTEN/Akt axis. In summary, the present findings revealed that lncRNA GAS5 has a radiosensitization effect on NSCLC, indicating the potential application of lncRNA GAS5 in NSCLC radiotherapy.

Preparation of CdTe superparticles for white light-emitting diodes without Förster resonance energy transfer.

Due to many unique and excellent optical properties, quantum dots (QDs) have been seen as one of the most promising color conversion materials in light-emitting diodes (LEDs). However, the Förster resonance energy transfer (FRET) among different colored QDs always causes a significant red-shift of the fluorescence emission, impeding the fabrication of LEDs with predicted photoluminescence (PL) emission spectra. In this work, we take advantage of CdTe superparticles (SPs), which are assembled by CdTe QDs, as the color conversion materials for the fabrication of WLEDs. Because of their submicron size, the distance between QDs with different emissions can be large enough to avoid the FRET process. More importantly, this method provides us with an opportunity to precisely design and regulate the PL emission spectra of LEDs. By easily overlapping the individual PL spectra of CdTe SPs with different emissions, the certain ratio of their usage for fabricating LEDs with desired PL emission spectra is identified. According to this idea, a WLED with a color rendering index (CRI) of 81, luminous efficacy of 27 lm W-1, and color coordinate at (0.33, 0.34) with the color temperature of 5742 K is achieved.

Multifunctional Supramolecular Materials Constructed from Polypyrrole@UiO-66 Nanohybrids and Pillararene Nanovalves for Targeted Chemophotothermal Therapy.

Multifunctional supramolecular nanomaterials capable of targeted and multimodal therapy hold great potential to improve the efficiency of cancer therapeutics. Herein, we report a proof-of-concept nanoplatform for effective chemophotothermal therapy via the integration of folic acid-based active targeting and supramolecular nanovalves-based passive targeting. Inspired by facile surface engineering and designable layer-by-layer assembly concept, we design and synthesize PPy@UiO-66@WP6@PEI-Fa nanoparticles (PUWPFa NPs) to achieve efficient synergistic chemophotothermal therapy, taking advantage of the desirable photothermal conversion capability of polypyrrole nanoparticles (PPy NPs) and high drug-loading capacity of hybrid scaffolds. Significantly, pillararene-based pseudorotaxanes as pH/temperature dual-responsive nanovalves allow targeted drug delivery in pathological environment with sustained release over 4 days, which is complementary to photothermal therapy, and folic acid-conjugated polyethyleneimine (PEI-Fa) at the outmost layer through electrostatic interactions is able to enhance tumor-targeting and therapeutic efficiency. Such PUWPFa NPs showed efficient synergistic chemophotothermal therapy of cervical cancer both in vitro and in vivo. The present strategy offers not only the distinctly targeted drug delivery and release, but also excellent tumor inhibition efficacy of simultaneous chemophotothermal therapy, opening a new avenue for effective cancer treatment.

Radiation inhibits salivary gland function by promoting STIM1 cleavage by caspase-3 and loss of SOCE through a TRPM2-dependent pathway.

Store-operated Ca2+ entry (SOCE) is critical for salivary gland fluid secretion. We report that radiation treatment caused persistent salivary gland dysfunction by activating a TRPM2-dependent mitochondrial pathway, leading to caspase-3-mediated cleavage of stromal interaction molecule 1 (STIM1) and loss of SOCE. After irradiation, acinar cells from the submandibular glands of TRPM2+/+ , but not those from TRPM2-/- mice, displayed an increase in the concentrations of mitochondrial Ca2+ and reactive oxygen species, a decrease in mitochondrial membrane potential, and activation of caspase-3, which was associated with a sustained decrease in STIM1 abundance and attenuation of SOCE. In a salivary gland cell line, silencing the mitochondrial Ca2+ uniporter or caspase-3 or treatment with inhibitors of TRPM2 or caspase-3 prevented irradiation-induced loss of STIM1 and SOCE. Expression of exogenous STIM1 in the salivary glands of irradiated mice increased SOCE and fluid secretion. We suggest that targeting the mechanisms underlying the loss of STIM1 would be a potentially useful approach for preserving salivary gland function after radiation therapy.

[Expression of MMP-2 in the periodontal tissues with the mini-screw for molar intrusion with cyclic intrusive force in dogs].

PURPOSE: To observe the expression of MMP-2 in the periodontal tissues of molars in Beagle dogs after different times of intrusion by mini-screw with cyclic intrusive force. METHODS: Three mature Beagle dogs were used for the experiment. On the buccal and palatal sites of the left maxillary second and third premolars, a minis-crew was placed at the inter-radicular septa separately, intruding the tooth with 150 g initial force, which would be reinforced every 4 weeks. The teeth of left side as the experimental group were divided into 3 subgroups, as being intruded 12, 24 and 36 weeks, and the right side as blank control. Then the dogs were sacrificed, and the second and the third premolars with the surrounding periodontal tissue were cut down, fixed, decalcified, wrapped and cut into slices. Immunohistochemical staining with MMP-2 was performed. The average optical density (OD) of MMP-2 was calculated with IPP software, which represented the expression of MMP-2. SPSS 17.0 software package was used for statistical analysis. RESULTS: Immunohistochemical staining revealed that the expression of MMP-2 in control group was low. After tooth intrusion, MMP-2 expression significantly increased in the periodontal tissues of molars, and reached the maximum in the group of 24 weeks. Then MMP-2 expression decreased in the 36-week group but still significantly higher than the control group. There was no significant difference among the 3 subgroups for different intrusion times(P>0.05). CONCLUSIONS: MMP-2 participates in remodeling of the periodontal tissue during tooth intrusion. The expression of MMP-2 is not significantly increased with the extension of the intrusion time with cyclic intrusive force, which suggests that with the use of mini-screw to intrude the molars with cyclic intrusive force, the periodontal tissues of the intruded tooth maintain dynamic balance of bone remodeling.

Decreased saliva secretion and down-regulation of AQP5 in submandibular gland in irradiated rats.

The molecular mechanisms of radiation-induced xerostomia remain unclear. The purpose of this study was to investigate the alterations of aquaporins (AQPs) and Na(+)/K(+)-ATPase in irradiated rat submandibular glands and to test the hypothesis that down-regulation of AQP5 expression in irradiated salivary glands is one of the mechanisms of radiation-induced xerostomia. Saliva from control and irradiated rat submandibular glands was analyzed. The mRNA level of AQP5 in the submandibular glands was assessed by semi-quantitative RT-PCR and in situ hybridization. The protein expression of AQP5, AQP1 and Na(+)/K(+)-ATPase was determined by Western blotting and immunohistochemistry. The body weight, submandibular gland weight, and saliva secretion of irradiated rats significantly decreased by 12, 24 and 32% on day 3 and 24, 16 and 38% on day 30 postirradiation, respectively. There was a significant increase in the protein concentration and osmolality of saliva in irradiated rats on days 3 and 30 postirradiation. However, there was no significant difference between irradiated and control rats in total saliva protein secretion. RT-PCR analysis showed that mRNA expression of AQP5 was significantly down-regulated by 37 and 51% in irradiated rats on days 3 and 30 postirradiation, respectively. Immunoblotting showed that the AQP5 protein level was decreased by 40 and 60% in irradiated glands, in contrast to the slight reductions of AQP1 and Na(+)/K(+)-ATPase proteins. Immunohistochemical analysis demonstrated that loss of AQP5 protein occurred throughout the irradiated glands, while no significant reduction was detected in AQP1 and Na(+)/ K(+)-ATPase labeling density. These results suggest that the preferential down-regulation of AQP5 with minor effects on AQP1 and Na(+)/K(+)-ATPase may contribute to radiation-induced salivary dysfunction.