Use of 3D printing models for donor tooth extraction in autotransplantation cases.

OBJECTIVE: To clarify whether the 3D printing model has auxiliary functions in toto extraction of donor tooth in autotransplantation cases. METHODS: Two hundred and sixty patients who would have operation of ATT were divided into two groups. In group 1, determination of the tooth extraction in toto was predicted only according to the clinical and imaging examination. In group 2, the prediction was performed according to the clinical and imaging examination as well as the 3D model of donor tooth pre-extraction. A prespctive clinical study was designed on intra-group comparison between the predicted and actual donor teeth situation when extraction in cases of ATT. The consistent rate for the predicted results and the actual results were compared with the two groups. RESULTS: A remarkable difference was observed between the predicted results and the actual results of tooth positions and root numbers in group without model (p < 0,05). The consistency rate of the model group (94.62%) was significantly higher than that of non 3D model group (86.15%) (p = 0.034). CONCLUSION: The 3D printing model for the donor tooth is helpful for dentists to predict the accuracy of toto extraction of donor teeth in autotransplantation cases.

Role of Gastrointestinal Microbiota from Crucian Carp in Microbial Transformation and Estrogenicity Modification of Novel Plastic Additives.

Ingestion is a major exposure route for hydrophobic organic pollutants in fish, but the microbial transformation and estrogenic modification of the novel plastic additives by the gut microbiota of fish remain obscure. Using an in vitro approach, we provide evidence that structure-related transformation of various plastic additives by the gastric and intestinal (GI) microbiota from crucian carp, with the degradation ratio of bisphenols and triphenyl phosphate faster than those of brominated compounds. The degradation kinetics for these pollutants could be limited by oxygen and cometabolic substrates (i.e., glucose). The fish GI microbiota could utilize the vast majority of carbon sources in a Biolog EcoPlate, suggesting their high metabolic potential and ability to transform various organic compounds. Unique microorganisms associated with transformation of the plastic additives including genera of Citrobacter, Klebsiella, and some unclassified genera in Enterobacteriaceae were identified by combining high-throughput genetic analyses and metagenomic analyses. Through identification of anaerobic transformation products by high-resolution mass spectrometry, alkyl-cleavage was found the common transformation mechanism, and hydrolysis was the major pathway for ester-containing pollutants. After anaerobic incubation, the estrogenic activities of triphenyl phosphate and bisphenols A, F, and AF declined, whereas that of bisphenol AP increased.

TMT-labelled quantitative proteomic analysis to predict the target promoting human odontogenic inflammatory granulation tissue transform into reparative granulation tissue.

OBJECTIVES: Odontogenic inflammatory diseases are main causes for alveolar bone breakdown and teeth loss, leaving great difficulties in denture restoration. Local inflammatory granulation tissue (IGT) is considered as pathological tissue and required to be removed. However, there are many evidences supporting that under appropriate intervention, IGT in alveolar bone maybe transformed into reparative granulation tissue (RGT), followed by ossification. Therefore, this study aimed to discover a specific target to promote this transformation. MATERIALS AND METHODS: After drawing out histological differences between IGT and RGT with haematoxylin and eosin (H&E) and immunohistochemical (IHC) assay staining, TMT-labelled quantitative proteomic analysis was applied to identify potential targets. RESULTS: The most striking histological property of RGT was found to be ECM deposition, which significantly decreased inflammatory cells, prominently increased fibroblasts as well as triggered changes of vascular types. Combined with histological findings and proteomic analysis, five KEGG pathways were associated with ECM, inflammation and angiogenesis and 49 pathways involved in differentially expressed proteins. COL1A1 was not only the most up-regulated protein, but also one of main hubs in protein-protein interaction regulatory network. Specific protease cathepsin K (CTSK) was identified. Level of CTSK in RGT was down-regulated to 69.10-76.97% (p < .05), with significantly up-regulated COL1A1, COL1A2, FN1 and TGFB1 included in focal adhesion, PI3K-Akt signalling pathways and angiogenesis. CTSK involved in transformation from IGT to RGT. CONCLUSIONS: CTSK might be a target to regulate transformation from IGT to RGT in alveolar bone through ECM, stem cells and angiogenesis mechanisms. However, further research is also clearly required.

Advances in exosome isolation methods and their applications in proteomic analysis of biological samples.

Exosomes are membrane-bound vesicles secreted by cells, and contain various important biological molecules, such as lipids, proteins, messenger RNAs, microRNAs, and noncoding RNAs. Emerging evidence demonstrates that proteomic analysis of exosomes is of great significance in studying metabolic diseases, tumor metastasis, immune regulation, and so forth. However, exosome proteomic analysis has high requirements with regard to the purity of collected exosomes. Here recent advances in the methods for isolating exosomes and their applications in proteomic analysis are summarized. Graphical abstract.

The Past, Present, and Future of Dentoalveolar Surgery in China.

Dentoalveolar surgery, formerly known as dental surgery or oral surgery, is one of the basic branches of oral and maxillofacial surgery. While it has a long history; however, there are great differences in its evolution globally. This article presents a brief review on the development of dentoalveolar surgery internationally. Furthermore, a systematic review on its development in China, is detailed in 6 stages. However, while its development in China since 2005 has been most profound, improvements are still needed in treatment concepts, instruments, treatment processes, attention to high-risk populations and cooperation with other dental/medical disciplines. Future projections based on present standards of care are also presented.

Targeting P38 Pathway Regulates Bony Formation via MSC Recruitment during Mandibular Distraction Osteogenesis in Rats.

Distraction osteogenesis (DO) is a widely used self-tissue engineering. However, complications and discomfort due to the long treatment period are still the bottleneck of DO. Novel strategies to accelerate bone formation in DO are still needed. P38 is capable of regulating the osteogenic differentiation of both mesenchymal stem cells (MSCs) and osteoblasts, which are crucial to bone regeneration. However, it is not clear whether targeting p38 could regulate bony formation in DO. The purpose of the current work was to investigate the effects of local application of either p38 agonist anisomycin or p38 inhibitor SB203580 in a rat model of DO. 30 adult rats were randomly divided into 3 groups: (A) rats injected with DMSO served as the control group; (B) rats injected with p38 agonist anisomycin; (C) rats injected with p38 inhibitor SB203580. All the rats were subjected to mandibular distraction and the injection was performed daily during this period. The distracted mandibles were harvested on days 15 and 30 after surgery and subjected to the following analysis. Micro-computed tomography and histological evaluation results showed that local application of p38 agonist anisomycin increased new bone formation in DO, whereas p38 inhibitor SB203580 decreased it. Immunohistochemical analysis suggested that anisomycin promoted MSC recruitment in the distraction gap. In conclusion, this study demonstrated that local application of p38 agonist anisomycin can increase new bone formation during DO. This study may lead to a novel cell-based strategy for the improvement of bone regeneration.

Alveolar ridge preservation with deproteinized bovine bone graft and collagen membrane and delayed implants.

To evaluate clinically and radiographically an alveolar ridge, preservation technique with deproteinized bovine bone graft and absorbable collagen membrane and then restoration with delayed implants were done. The study included 30 patients. The trial group's sockets were filled with deproteinized bovine bone graft (Bio-Oss) and covered with absorbable collagen membrane (Bio-Gide). The control group's sockets healed without any treatment. Panoramic radiograph and computed tomography were taken immediately after graft and 3 and 6 months later to evaluate the height, width, and volume change of the alveolar ridge bone. Dental implants were inserted in all sockets at 6 months, and osseointegration condition was evaluated in the following 12 months. All sockets healed uneventfully. In the trial group, the mean (SD) height reduction of the alveolar ridge bone was 1.05 (0.24) mm at 3 months and 1.54 (0.25) mm at 6 months. The width reduction was 1.11 (0.13) mm at 3 months and 1.84 (0.35) mm at 6 months. Bone volume reduction was 193.79 (21.47) mm at 3 months and 262.06 (33.08) mm at 6 months. At the same trend, in the control group, the bone height reduction was 2.12 (0.15) mm at 3 months and 3.26 (0.29) mm at 6 months. The width reduction was 2.72 (0.19) mm at 3 months and 3.56 (0.28) mm at 6 months. Bone volume reduction was 252.19 (37.21) mm at 3 months and 342.32 (36.41) mm at 6 months. There was a significant difference in alveolar ridge bone height, width, and volume reduction in the 2 groups. The osseointegration condition had no significant difference between the 2 groups. This study suggested that the deproteinized bovine bone graft and absorbable collagen membrane were beneficial to preserve the alveolar ridge bone and had no influence on the osseointegration of delayed implant.

Responses of methane production and methanogenic pathways to polystyrene nanoplastics exposure in paddy soil.

Nanoplastics (NPs) have attracted increasing attention within terrestrial ecosystems. However, our understanding of their impacts on the intricate anaerobic methanogenesis processes occurring in paddy soils microbial communities remains limited with respect to nanoplastics shape, function, and metabolic effects. Herein, we explored the effects of polystyrene nanoplastics (PS-NPs) and microplastics (PS-MPs) on anaerobic methanogenesis in a typical paddy soil. The results show that PS-NPs delayed methane production and the time to reach peak acetate content in incubation process of paddy soils, and the methanogenic rate increased rapidly after 13 days, with a maximum increase of 87.97%. However, PS-MPs had no marked effect on CH4, CO2 and acetate production. In addition, PS-NPs affected soil physicochemical properties by reducing pH and increasing electrical conductivity. Acetoclastic methanogens were enriched and the relative abundance of the genes ackA, pta, ACSS, cdhC, cdhD and cdhE in the acetoclastic pathways were significantly increased under PS-NPs exposure. In addition, PS-MPs had significant effect on the microbial community structure but no effect on methanogenic pathways of the paddy soils. This study provides important insights into the response of key microorganisms, functional genes and methanogenesis pathways to NPs during anaerobic methanogenesis in paddy soils.

Atmospheric microplastics at a southern China metropolis: Occurrence, deposition flux, exposure risk and washout effect of rainfall.

Atmospheric microplastics (AMPs) have raised much concern for public health due to their potential for exposure. In this study, temporal distribution, characteristics and exposure risk of AMPs were studied in the urban area of Guangzhou, a metropolis in Southern China, and the washout effect of rainfall on AMPs was investigated. It was found that AMP abundances in Guangzhou were in a range of 0.01-0.44 items/m3, with higher abundance in the wet season (0.19 ± 0.01 items/m3) than in the dry season (0.15 ± 0.02 items/m3). The distribution of AMPs did not correspond to that of common air pollutants (e.g., PM2.5 and PM10), implying that their pollution sources might be distinct. In Guangzhou, a total of 1.26 × 1011 items AMPs are in the air every year, and annual inhalation exposure of adults was estimated to be in the range of 79.65-3.50 × 103 items. The annual deposition flux of AMPs is 65.94 ± 7.53 items/m2/d, and the deposition flux in the wet season (84.00 ± 6.95 items/m2/d) was much greater than that in the dry season (47.88 ± 8.35 items/m2/d). Furthermore, rainfall has an effective mechanism for removing AMPs from the atmosphere, with an average washout ratio of (19.39 ± 6.48) × 104 for rainfall washing AMPs out. Compared to moderate rain (2.5-10 mm/h) and heavy rain (10-50 mm/h), light rain (rainfall intensity <2.5 mm/h) had a better washout effect. This study contributes to the evaluation of AMP exposure risk and understanding of AMP environmental behavior and fate by providing long-term monitoring data on AMPs and quantifying the washout effect of rainfall on AMPs for the first time.

Expanded polystyrene buoys as an important source of hexabromocyclododecanes for aquatic ecosystem: Evidence from field exposure with different substrates.

The production and use of hexabromocyclododecanes (HBCDs) have been strictly limited due to their persistence, toxicity and bioaccumulation. However, the release of HBCDs from related products and wastes would continue for a long time, which may cause many environmental problems. In this study, we investigated the occurrence and distribution of HBCDs and microplastics (MPs) in aquatic organisms inhabiting different substrates. HBCDs were measurable in the seawater, sediment, expanded polystyrene (EPS) substrates and organism samples. Mostly, the concentrations of HBCDs in organisms inhabiting EPS buoys were significantly higher than those of the same species inhabiting other substrates. Meanwhile, the diastereomeric ratio (α/γ) of HBCDs in organisms inhabiting EPS buoys was closer to that in EPS buoys. The fugacity values of HBCDs in EPS buoys were much higher than those in other media, implying that HBCDs can be transferred from EPS buoys to other media. Additionally, MPs derived from EPS buoys would be mistaken as food and ingested by aquatic organisms. The transfer of HBCDs from EPS buoys to aquatic organisms can be achieved by aqueous and dietary exposures. In combination, the contribution of MP ingestion to HBCDs for aquatic organisms should be very limited. These results supported EPS buoys as an important source of HBCDs for the aquatic ecosystem. To effectively control HBCDs pollution, it is necessary to discontinue or reduce the use of EPS buoys.

Secondary healing after removal of large keratocystic odontogenic tumor in the mandible: enucleation followed by open packing of iodoform gauze.

PURPOSE: The aim of this retrospective study was to present the findings of an open packing method after enucleation of large keratocystic odontogenic tumors (KCOTs) in the mandible. PATIENTS AND METHODS: We performed a retrospective case series study of 27 patients with KCOTs larger than 5 cm treated at our institution between September 2003 and September 2008. A conservative surgical treatment was applied, which involved enucleation of the primary lesion and open packing of the residual osseous defect with iodoform gauze for secondary healing. Bone regeneration, tumor recurrence, and surgical complications were observed and analyzed. We used the χ(2) test and Pearson correlation coefficient for statistical analysis. RESULTS: The postoperative follow-up time was 52.3 months on average (range, 24 to 84 months). The packing gauze was changed every 2 weeks after enucleation, and the total duration for packing was 10.2 months on average (range, 7-15 months). Bone regeneration and satisfactory secondary healing were observed clinically and radiographically after treatment. Only 1 case had a recurrence 6 months after initial treatment, which was attributed to insufficient bony unroofing during enucleation. The recurrent lesion was re-treated by the same method, and no recurrence occurred in the following 6 years. No serious complications from this method of treatment were observed. No significant variables were found to be related to the recurrence. CONCLUSIONS: Enucleation with subsequent open packing was shown to be a conservative and comfortable treatment for patients and appears to be an effective choice for the management of large KCOTs in the mandible.

Surfactant-sodium dodecyl sulfate enhanced degradation of polystyrene microplastics with an energy-saving electrochemical advanced oxidation process (EAOP) strategy.

Microplastics have been identified as a kind of emerging pollutant with potential ecological risks, and it is an urgent endeavor to find proper technologies for their remediation. Electrochemical advanced oxidation process (EAOP) technology has exhibited robust performance in the removal of various refractory organic pollutants. In this study, we explored a new remediation strategy for polystyrene microplastics (PS MPs), introducing sodium dodecyl sulfate (SDS) to enhance its degradation performance in boron-doped diamond (BDD) anode adopted EAOP. At first, we investigated the degradation behaviors of SDS in the BDD electrolysis. According to the SDS half-life under various current densities, the SDS addition strategy into EAOP is proposed; that is, supplement SDS to 500 mg/L at every half-life during electrolysis except the last cycle. Results indicated that SDS addition greatly enhanced MPs degradation rate in 72 h of EAOP, about 1.35-2.29 times higher than that in BDD electrolysis alone. The SDS assisted EAOP also led to more obvious changes in the particle size, morphology, and functional groups of the MPs. After treatment, a variety of alkyl-cleavage and oxidation products were identified, which attributed to the strong attack of oxidants (i.e., persulfate) on the MPs. The enhanced persulfate generation and oxidants adsorption on MPs can explain the enhancement effect in the EAOP strategy. Cost analysis results showed the surfactant only accounts for < 0.05% of the total operating costs in the SDS assisted EAOP. In general, the current study provided new insight into the effective way to improve the EAOP efficiency of microplastics.

Microplastics contamination in bivalves from the Daya Bay: Species variability and spatio-temporal distribution and human health risks.

Microplastic contamination is an emerging global threat for various marine organisms. Marine invertebrates such as bivalve mollusks are more susceptible to the widespread presence of microplastics due to their limited abilities to escape from pollution exposure and they can readily ingest environmental pollutants like microplastics through their filter-feeding behaviors. In this study, microplastic contamination in bivalves related to species, spatial, and temporal variability were conducted. Results showed that the frequency of microplastic occurrence varied from 86.7 % to 93.3 % in six species of bivalves, and the average abundance of microplastics ranged from 3.5 to 8.6 items per individual or from 0.2 to 3.1 items per gram tissues wet weight. No significant difference was observed in microplastic abundances of bivalves collected from different research regions and sampling seasons. However, the sediment-dwelling bivalves had higher microplastics abundances than the water-dwelling bivalves. Microplastic features with various shapes, colors, sizes, and polymer types detected in bivalves were similar with those in seawater and sediment environments that they are living in. The potential risk assessment of microplastics in bivalves basing on polymer hazard index (PHI) was in the risk levels of II-III, implying that microplastic contamination in bivalves may pose health risk to human via seafood consumption.

Microplastic pollution in the surface seawater in Zhongsha Atoll, South China Sea.

The prevalence of microplastics in the marine environment has attracted extensive attention. So far, no information is known regarding the temporal and spatial variations of microplastics in Zhongsha Atoll. This study, for the first time, comprehensively investigated the occurrence and distribution of microplastics in the surface seawater in Zhongsha Atoll based on two ocean cruises. The abundances of microplastics measured in the surface seawater of Zhongsha Atoll were in the ranges of not detected (ND) to 67 items/m3, and ND to 160 items/m3 in 2019 and 2020, respectively. All microplastics detected in Zhongsha Atoll were fibers, most of which were transparent and less than 2 mm. Polyethylene terephthalate was the dominating composition of microplastics. These results suggested that sewage, surface runoff, atmospheric deposition by neighboring land, and fishing activities may be the primary pollution sources. This study provides critical information on microplastic pollution in Zhongsha Atoll for the first time, calling for more research in the management of marine plastic debris in the future.

Biological detoxification of different hemicellulosic hydrolysates using Issatchenkia occidentalis CCTCC M 206097 yeast.

This work had as its main objective to contribute to the development of a biological detoxification of hemicellulose hydrolysates obtained from different biomass plants using Issatchenkia occidentalis CCTCC M 206097 yeast. Tests with hemicellulosic hydrolysate of sugarcane bagasse in different concentrations were carried out to evaluate the influence of the hydrolysate concentration on the inhibitory compounds removal from the sugarcane bagasse hydrolysate, without reduction of sugar concentration. The highest reduction values of inhibitors concentration and less sugar losses were observed when the fivefold concentrated hydrolysate was treated by the evaluated yeast. In these experiments it was found that the high sugar concentrations favored lower sugar consumption by the yeast. The highest concentration reduction of syringaldehyde (66.67%), ferulic acid (73.33%), furfural (62%), and 5-HMF (85%) was observed when the concentrated hydrolysate was detoxified by using this yeast strain after 24 h of experimentation. The results obtained in this work showed the potential of the yeast Issatchenkia occidentalis CCTCC M 206097 as detoxification agent of hemicellulosic hydrolysate of different biomass plants.

Investigation of impacted permanent teeth except the third molar in Chinese patients through an X-ray study.

PURPOSE: To investigate the incidence and the local factors of impacted permanent teeth, except for the third molar, in Chinese patients through an x-ray study. MATERIALS AND METHODS: A total of 548 impacted permanent teeth from panoramic radiographs were studied and recorded according to the patients' gender and age, tooth position, and classification of impaction. The local factors contributing to impacted permanent tooth were also investigated. RESULTS: The incidence of impacted permanent teeth in the Chinese was 6.15%. The impacted tooth showed a predilection for women and was more common in the maxilla. The impaction of the canine had the greatest occurrence, 28.10% of all impacted teeth. Vertical impaction was most common (49.09%). The chief local factor for impacted teeth was the lack of interdental space (49.64%). CONCLUSIONS: All permanent teeth can occur with impaction in Chinese patients. Dentists should perform a thorough evaluation before planning suitable treatment.

Effects of nerve growth factor delivery via a gel to inferior alveolar nerve in mandibular distraction osteogenesis.

Inferior alveolar nerve (IAN) injury is a concern in mandible distraction osteogenesis (DO). We have previously demonstrated that repeated local injections of human nerve growth factor beta (NGF-beta) have significantly enhanced the histologic recovery of the IAN in a rabbit model of DO. This study was to further test the effect of a single injection of human NGF-beta delivered via a collagen/nanohydroxyapatite/kappa-carrageenan gel to the recovery of the IAN in DO. Rabbits underwent mandibular DO at a rate of 0.75 mm/12 h for 6 days. At the end of the distraction period, injections were performed near the IAN percutaneously as follows: group 1, human NGF-beta in the gel; group 2, human NGF-beta in saline; group 3, the gel alone; and group 4, saline alone. At 14 days after the end of distraction, IAN histologic findings and histomorphometric parameters were evaluated. Histologically, there were less myelin debris and more abundant regenerating nerve fibers in group 1 than the other groups. Both the myelinated fiber density and the myelinated axon area in group 1 were significantly higher than groups 3 and 4 (P < 0.01); the myelinated axon area in the group 1 was significantly higher than group 2 (P < 0.01). In conclusion, the delivery of human NGF-beta in the gel leads to a better acceleration of the IAN injury recovery over the saline delivery. It provides a possible way to enhance the recovery of nerve injuries in craniofacial DO clinically.

Highly stable near-infrared dye conjugated cerasomes for fluorescence imaging-guided synergistic chemo-photothermal therapy of colorectal cancer.

Colorectal cancer is a common malignant tumour with a low 5-year survival rate. A combination therapy with high selectivity and easy controllability is a pressing need for the effective treatment of such cancer. In this study, an indocyanine green derivative (Cy7)-conjugated lipid with a terminal carboxyl group was synthesized, which could self-assemble with a cerasome-forming lipid (CFL) into nanoparticles (NPs) by encapsulating doxorubicin (DOX) to achieve combined photothermal chemotherapy. The resulting Gly@Cy7-Si-DOX NPs with a surface covalent silicate framework showed excellent morphological stability and colloidal stability. Specifically, the conjugated Cy7 was covalently conjugated in the liposomal bilayer, resulting in high drug loading content, high photostability, and high photothermal conversion efficiency, which enabled the resulting nanoparticles to be an effective platform for photothermal therapy. Meanwhile, the encapsulated DOX leaked only slightly under physiological conditions due to the silicate surface of Gly@Cy7-Si-DOX NPs and exhibited controlled release in a weakly acidic environment or under near-infrared (NIR) light irradiation for chemotherapy. Gly@Cy7-Si-DOX NPs were efficiently taken up by tumour cells. Upon light irradiation, the released DOX entered the nuclei of tumour cells, as observed by confocal microscopy and flow cytometry. In vitro cell experiments indicated that both healthy cells and tumour cells were viable under treatment with only Gly@Cy7-Si-DOX NPs, indicating the encapsulated DOX was stably confined to the NPs, and cells were significantly killed when treated with both Gly@Cy7-Si-DOX NPs and NIR laser irradiation. After i.v. administration, Gly@Cy7-Si-DOX NPs accumulated at the tumour site, as monitored by near-infrared fluorescence imaging. A significant tumour inhibition rate (95.8%) was also achieved in a HT-29 colorectal cancer model when treated with Gly@Cy7-Si-DOX NPs plus irradiation. Therefore, the Gly@Cy7-Si-DOX NPs hold great promise for controllable combined colorectal cancer photothermal chemotherapy.

Calcitonin gene-related peptide enhances osteogenic differentiation and recruitment of bone marrow mesenchymal stem cells in rats.

The present study evaluated the effects of calcitonin gene-related peptide (CGRP) on bone marrow mesenchymal stem cells (BMMSCs) in vitro and in a rat model of mandibular distraction osteogenesis (MDO). Rat BMMSCs were isolated then treated with CGRP or CGRP antagonist (CGRP8-37). The proliferation and migration ability of BMMSCs was determined using 5-bromo-2'-deoxyuridine and Transwell assays, respectively. Osteogenic-related gene expression was analyzed with reverse transcription-quantitative polymerase chain reaction. For the in vivo analysis, thirty MDO rats were randomly assigned to control, CGRP or CGRP8-37 groups. To evaluate the mobilization of BMMSCs, nestin and stromal cell-derived factor 1 (SDF-1) were detected by immunohistochemistry and ELISA. Rats were sacrificed following 14 days and new bone formation was assessed by histological and micro-computed tomography analysis. In the in vitro results, the CGRP group demonstrated significantly higher migration and proliferation, as well as enhanced alkaline phosphatase and runt-related transcription factor 2 expression compared with the control. In the in vivo experiments, bone mineral density of the newly formed bone in the CGRP group was significantly higher than controls. The nestin and SDF-1 expression in the CGRP group was also significantly upregulated. In conclusion, the present study demonstrated that CGRP administration increased new bone formation, possibly via enhancing BMMSC migration and differentiation in MDO rats.

Host-Guest Polypyrrole Nanocomplex for Three-Stimuli-Responsive Drug Delivery and Imaging-Guided Chemo-Photothermal Synergetic Therapy of Refractory Thyroid Cancer.

Despite the good prognosis of the low-risk thyroid cancer, there are no truly effective treatments for radioactive iodine-refractory thyroid cancer. Herein, a novel theranostic nanoplatform, as well as a smart doxorubucin (DOX) delivery system is fabricated. Gelatin-stabilized polypyrrole nanoparticles are reported for the first time. The combination of gelatin-stabilized polypyrrole and cyclodextrin-DOX complexes enabling three-stimuli-controlled drug delivery, including the enzyme-sensitive, pH-sensitive and photothermal-sensitive drug release, exhibiting a new way to equip photothermal agents with precisely controlled drug delivery. Anti-galectin-3 antibodies are utilized as the targeting molecules of nanoparticles in the first time, which surprisingly increase intracellular DOX uptake by enhanced clathrin-mediated endocytosis, showing galectin-3 can be employed as a highly efficient target of drug delivery systems. The nanoparticles achieve excellent photoacoustic imaging effect, enabled chemo-photothermal combined therapy with pinpointed drug delivery. Compared to free DOX, these multifunctional nanoparticles decrease the heart damage, but greatly increase the tumor/heart ratio of DOX concentration by 12.9-fold. The tumors are completely eradicated without any recurrence after the in vivo combined therapy. To the best of the authors' knowledge, this is also the first report to apply photoacoustic imaging-guided chemo-photothermal therapy for thyroid cancer, showing great potential to solve the dilemma in thyroid cancer therapy.