Electrical modulation properties of DNA drug molecules.

DNA drug molecules are not only widely used in gene therapy, but also play an important role in controlling the electrical properties of molecular electronics. Covalent binding, groove binding and intercalation are all important forms of drug-DNA interaction. But its applications are limited due to a lack of understanding of the electron transport mechanisms after different drug-DNA interaction modes. Here, we used a combination of density functional theory calculations and nonequilibrium Green's function formulation with decoherence to study the effect of drug molecules on the charge transport property of DNA under three different binding modes. Conductance of DNA is found to decrease from 2.35E-5 G0 to 1.95E-6 G0 upon doxorubicin intercalation due to modifications of the density of states in the near-highest occupied molecular orbital region, δG = 1105.13%. Additionally, the conductance of DNA after cis-[Pt(NH3)2(py)Cl]+ covalent binding increases from 1.02E-6 G0 to 5.25E-5 G0, δG = 5047.06%. However, in the case of pentamidine groove binding, because there is no direct change in DNA molecular structure during drug binding, the conductance changes before and after drug binding is much smaller than in the two above cases, δG = 90.43%. Our theoretical calculations suggest that the conductance of DNA can be regulated by different drug molecules or switching the interaction modes between small molecules and DNA. This regulation opens new possibilities for their potential applications in controllable modulation of the electron transport property of DNA.

Macrophage Activation in Synovitis and Osteoarthritis of Temporomandibular Joint and Its Relationship with the Progression of Synovitis and Bone Remodeling.

This study investigates the regulatory mechanisms of synovial macrophages and their polarization in the progression of temporomandibular joint osteoarthritis (TMJOA). Macrophage depletion models were established by intra-articular injection of clodronate liposomes and unloaded liposomes. TMJOA was induced by intra-articular injection of 50 µL Complete Freund's Adjuvant and the surgery of disc perforation. The contralateral joint was used as the control group. The expression of F4/80, CD86, and CD206 in the synovium was detected by immunofluorescence staining analysis. Hematoxylin and eosin staining and TMJOA synovial score were detected to show the synovial changes in rat joints after TMJOA induction and macrophage depletion. Changes in rat cartilage after TMJOA induction and macrophage depletion were shown by safranin fast green staining. The bone-related parameters of rats' joints were evaluated by micro-computed tomography analysis. The TMJOA model induced by Complete Freund's Adjuvant injection and disc perforation aggravated synovial hyperplasia and showed a significant up-regulation of expression of F4/80-, CD86-, and CD206-positive cells. F4/80, CD86, and CD206 staining levels were significantly decreased in macrophage depletion rats, whereas the synovitis score further increased and cartilage and subchondral bone destruction was slightly aggravated. Macrophages were crucially involved in the progression of TMJOA, and macrophage depletion in TMJOA synoviocytes promoted synovitis and cartilage destruction.

The relationship of ALPK1, hyaluronic acid and M1 macrophage polarization in the temporomandibular joint synovitis.

M1 macrophage polarization and synovitis play an important role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA). Reduced molecular weight of hyaluronic acid (HA) in synovial fluid of patients with TMJOA. In addition, high molecular weight hyaluronic acid (HMW-HA) is often used clinically to treat TMJ inflammation. As a pattern recognition receptor of the cytoplasm, ALPK1 was found to be pro-inflammatory in a variety of diseases. However, the relationship of ALPK1, HA and M1 macrophage polarization in TMJ synovitis remains unclear. We aimed to investigate the role of ALPK1 and HA in macrophage polarization and TMJ synovitis and the underlying mechanisms. The results demonstrated that ALPK1 was highly upregulated in the synovial macrophages in the inflamed TMJ synovium of patients. Low molecular weight hyaluronic acid (LMW-HA) promoted the expression of ALPK1 and M1 macrophage-associated genes. Besides, rhALPK1 promoted the expression of M1 macrophage-associated factors and the nuclear translocation of PKM2. Furthermore, ALPK1 knockout mice exhibited limited infiltration of macrophages and decreased expression levels of M1 macrophage-associated genes in CFA-induced TMJ synovitis. While HMW-HA inhibited the expression of ALPK1 and M1 macrophage polarization. Our results elucidated that ALPK1 promoted TMJ synovitis by promoting nuclear PKM2-mediated M1 macrophage polarization, whereas HMW-HA inhibited the expression of ALPK1 as well as M1 macrophage polarization.

High-performance Ag-TiO2 nanoparticle composite catalyst synthesized by pulsed laser ablation in liquid: properties, mechanism and preparation studies.

Precious metal doping can effectively improves the catalytic performance of TiO2. In this study, pulsed laser ablation in liquid (PLAL) is employed to integrate preparation with doping and control composite nanoparticle products by adjusting the laser action time to synthesise Ag-TiO2 composite nanoparticles with high catalytic performance. The generation and evolution of Ag-TiO2 nanoparticles are investigated by analysing particle size, microscopic morphology, crystalline phase, and other characteristics. The generation and doped-morphology evolution of composite nanoparticles are simulated based on thermodynamics, and the optimisation of Ag-doped structure on the composite nanomaterials is investigated based on density functional theory. The effect of Ag-TiO2 structural properties on its performance is examined under different catalytic conditions to determine optimal degradation conditions. In this study, the effect of laser ablation time on the doped structure during PLAL is analysed, which is of further research significance in exploring the structural evolution law of laser and composite nanoparticles, multi-variate catalytic performance testing, reduction of photogenerated carrier complexation rate, and expansion of its spectral absorption range, thereby providing the basis for practical production.

Fenton reaction in the process of "Laser + Fe" mode excited plasma for Rhodamine B degradation.

The spectral emission of laser-induced plasma in water has a broadband continuum containing ultraviolet light, which can be used as a novel light source for the degradation of organic compounds. We studied the degradation process of the organic dye Rhodamine B (RhB) using plasma light source excited by the "Laser + Fe" mode. Spectral analysis and reaction kinetics modelling were used to study the degradation mechanism. The degradation process using this light source could be divided into two stages. The initial stage was mainly photocatalytic degradation, where ultraviolet light broke the chemical bond of RhB, and then RhB was degraded by the strong oxidising ability of ·OH. As the iron and hydrogen ion concentrations increased, the synergistic effect of photocatalysis and the Fenton reaction further enhanced the degradation rate in the later stage. The plasma excited by the "Laser + Fe" mode achieved photodegradation by effectively enhancing the ultraviolet wavelength ratio of the emission spectrum and triggered the Fenton reaction to achieve rapid organic matter degradation. Our findings indicate that the participation of the Fenton reaction can increase the degradation rate by approximately 10 times. Besides, the impact of pH on degradation efficiency demonstrates that both acidic and alkaline environments have better degradation effects than neutral conditions; this is because acidic environments can enhance the Fenton reaction, while alkaline environments can provide more ·OH.

The effect of mindfulness-based cognitive therapy on the Clinical efficacy and psychological state in patients with functional dyspepsia.

BACKGROUND AND AIM: To observe the clinical therapeutic effect and mental state of mindfulness-based cognitive therapy (MBCT) in patients with functional dyspepsia (FD). METHODS: In this study, 80 patients suffering from FD in an outpatient clinic were enrolled from January to December 2020. Patients were randomly allocated into the control group (conventional treatment) and observation group (MBCT treatment). Patients in the control group were prescribed rabeprazole and mosapiride, and patients in the observation group were given MBCT therapy in addition to the above drugs. After treatment for 8 weeks, the changes in gastrointestinal symptom scores, anxiety, depression, mindfulness and sleep quality and gastric emptying testing were compared between these two groups. RESULTS: The observation group showed strikingly lower gastrointestinal symptom scores, SAS, SDS, PSQI, and SCL-90 scale scores, and higher FFMQ scale scores than the control group (p < 0.05). There was no conspicuous change in gastric emptying monitoring (p > 0.05). CONCLUSIONS: MBCT therapy can improve patients' gastrointestinal symptoms, attenuate their anxiety and depression levels, and ameliorate their sleep quality.

Mandibular Deviation With Longstanding Temporomandibular Joint Dislocation Caused by Lateral Pterygoid Muscle Hyaline Degeneration.

The present report described a rare case of mandible deviation with longstanding unilateral temporomandibular joint dislocation caused by lateral pterygoid muscle hyaline degeneration. A 28-year-old male was referred for mandible deviation for 2 years. It was found that the left condyle was dislocated just below the articular eminence with the dilated capsule in magnetic resonance imaging images. After surgical dissection of the lateral pterygoid muscle, which was excessively attached to the condyle, the left condyle was reduced, and the patient's mandibular deviation was greatly improved. The pathologic results showed lateral pterygoid muscle hyaline degeneration.

Glycyrrhizin regulates antioxidation through Nrf2 signaling pathway in rat temporomandibular joint osteoarthritis.

BACKGROUND: Regulation of redox homeostasis could reduce osteoarthritis severity and limit disease progression, while glycyrrhizin (GL) shows great antioxidant and anti-inflammatory capacity. OBJECTIVE: The aim of this study was to investigate the role of GL on oxidative stress and the potential regulatory mechanism in rat temporomandibular joint (TMJ) chondrocytes under oxidative stress, and investigate the effect of GL in the rat temporomandibular joint osteoarthritis (TMJOA) model. METHODS: Rat TMJ chondrocytes were cultured in oxidative stress with different doses of GL. The effect of glycyrrhizin on the nuclear factor-erythroid 2-related factor 2 (Nrf2) in oxidative stress was evaluated by western blot and immunofluorescence staining. A rat model of TMJOA was treated with GL. Micro-computed tomography, histological and immunohistochemical analysis were used to assess the pathological change of TMJOA. RESULTS: The expression of superoxide dismutase 1 (SOD1), heme oxygenase-1 (HO-1), and peroxiredoxin 6 (PRDX6) were decreased, and intracellular Nrf2 signaling pathway was activated in chondrocytes in oxidative stress. GL upregulates the expression of antioxidants, especially PRDX6, as well as increases Nrf2 expression and nuclear translocation in rat condylar chondrocytes. Administration of GL attenuates condylar bone destruction, cartilage degeneration, and synovitis in rats TMJOA. Meanwhile, GL alleviated oxidative stress and enhanced the antioxidant capacity of TMJOA cartilage. CONCLUSION: This study suggested that GL alleviates rat TMJOA by regulating oxidative stress in condylar cartilage.

Phomopsterone B Alleviates Liver Fibrosis through mTOR-Mediated Autophagy and Apoptosis Pathway.

Liver fibrosis is the initial pathological process of many chronic liver diseases. Targeting hepatic stellate cell (HSC) activation is an available strategy for the therapy of liver fibrosis. We aimed to explore the anti-liver fibrosis activity and potential mechanism of phomopsterone B (PB) in human HSCs. The results showed that PB effectively attenuated the proliferation of TGF-ß1-stimulated LX-2 cells in a concentration-dependent manner at doses of 1, 2, and 4 µM. Quantitative real-time PCR and Western blot assays displayed that PB significantly reduced the expression levels of α-SMA and collagen I/III. AO/EB and Hoechst33342 staining and flow cytometry assays exhibited that PB promoted the cells' apoptosis. Meanwhile, PB diminished the number of autophagic vesicles and vacuolated structures, and the LC3B fluorescent spots indicated that PB could effectively inhibit the accretion of autophagosomes in LX-2 cells. Moreover, rapamycin and MHY1485 were utilized to further investigate the effect of mTOR in autophagy and apoptosis. The results demonstrated that PB regulated autophagy and apoptosis via the mTOR-dependent pathway in LX-2 cells. In summary, this is the first evidence that PB effectively alleviates liver fibrosis in TGF-ß1-stimulated LX-2 cells, and PB may be a promising candidate for the prevention of liver fibrosis.

Terpenoids with Cytotoxic Activity from Roots of Ardisia crispa.

Three new terpenoids, ardisiacrispins G-I (1, 4 and 8), and eight known compounds, cyclamiretin A (2), psychotrianoside G (3), 3-hydroxy-ß-damascone (5), megastigmane (6), corchoionol C (7), zingiberoside B (9), angelicoidenol (10), trans-linalool-3,6-oxide-ß-D-glucopyranoside (11) were isolated from the roots of Ardisia crispa. The chemical structures of all isolated compounds were elucidated by extensive spectroscopic analyses, such as HR-ESI-MS, 1D and 2D NMR spectra. Ardisiacrispin G (1) represents the oleanolic-type scaffold featuring a rare 15,16- epoxy system. All compounds were evaluated for the cytotoxicity against two cancer cell lines (U87 MG and HepG2) in vitro. Compounds 1, 8 and 9 exhibited moderate cytotoxic activity with IC50 values ranging from 7.6±1.1 to 28.8±3.2 µM.

High-Strength, High-Water-Retention Hemicellulose-Based Hydrogel and Its Application in Urea Slow Release.

The use of fertilizer is closely related to crop growth and environmental protection in agricultural production. It is of great significance to develop environmentally friendly and biodegradable bio-based slow-release fertilizers. In this work, porous hemicellulose-based hydrogels were created, which had excellent mechanical properties, water retention properties (the water retention ratio in soil was 93.8% after 5 d), antioxidant properties (76.76%), and UV resistance (92.2%). This improves the efficiency and potential of its application in soil. In addition, electrostatic interaction and coating with sodium alginate produced a stable core-shell structure. The slow release of urea was realized. The cumulative release ratio of urea after 12 h was 27.42% and 11.38%, and the release kinetic constants were 0.0973 and 0.0288, in aqueous solution and soil, respectively. The sustained release results demonstrated that urea diffusion in aqueous solution followed the Korsmeyer-Peppas model, indicating the Fick diffusion mechanism, whereas diffusion in soil adhered to the Higuchi model. The outcomes show that urea release ratio may be successfully slowed down by hemicellulose hydrogels with high water retention ability. This provides a new method for the application of lignocellulosic biomass in agricultural slow-release fertilizer.

Effect of access cavities on the biomechanics of mandibular molars: a finite element analysis.

INTRODUCTION: This study aimed to predict the fracture resistance of a mandibular first molar (MFM) with diverse endodontic cavities using finite element analysis (FEA). METHODS: Five experimental finite element models representing a natural tooth (NT) and 4 endodontically treated MFMs were generated. Treated MFM models were with a traditional endodontic cavity (TEC) and minimally invasive endodontic (MIE) cavities, including guided endodontic cavity (GEC), contracted endodontic cavity (CEC) and truss endodontic cavity (TREC). Three loads were applied, simulating a maximum bite force of 600 N (N) vertically and a normal masticatory force of 225 N vertically and laterally. The distributions of von Mises (VM) stress and maximum VM stress were calculated. RESULTS: The maximum VM stresses of the NT model were the lowest under normal masticatory forces. In endodontically treated models, the distribution of VM stress in GEC model was the most similar to NT model. The maximum VM stresses of the GEC and CEC models under different forces were lower than those of TREC and TEC models. Under vertical loads, the maximum VM stresses of the TREC model were the highest, while under the lateral load, the maximum VM stress of the TEC model was the highest. CONCLUSION: The stress distribution of tooth with GEC was most like NT. Compared with TECs, GECs and CECs may better maintain fracture resistance, TRECs, however, may have a limited effect on maintenance of the tooth resistance.

Glycyrrhizin regulates rat TMJOA progression by inhibiting the HMGB1-RAGE/TLR4-NF-κB/AKT pathway.

To investigate the role of glycyrrhizin on the progression of temporomandibular joint osteoarthritis (TMJOA) and the underlying mechanism by regulation of the high-mobility group box 1 (HMGB1) receptor for advanced glycation end products (RAGE)/toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB)/protein kinase B (AKT) pathway. After a rat model of TMJOA was built by intra-articular injection of monosodium iodoacetate, glycyrrhizin was intragastrically administered at low concentration (20 mg/kg) or high concentration (50 mg/kg). Micro-computed tomography, histological and immunohistochemical analysis were used to reveal the progression of TMJOA. Rat TMJ chondrocytes and disc cells were cultured in inflammatory condition with different doses of glycyrrhizin. Western blot was used to evaluate the effect of glycyrrhizin on the HMGB1-RAGE/TLR4-NF-κB/AKT pathway. Administration of glycyrrhizin alleviated cartilage degeneration, lowered the levels of inflammatory and catabolic mediators and reduced the production of HMGB1, RAGE and TLR4 in TMJOA animal model. Increased production of RAGE and TLR4, and activated intracellular NF-κB and/or AKT signalling pathways in chondrocytes and disc cells were found in inflammatory condition. Upon activation, matrix metalloprotease-3 and interleukin-6 were upregulated. Glycyrrhizin inhibited not only HMGB1 release but also RAGE and TLR4 in inflammatory condition. Glycyrrhizin alleviated the pathological changes of TMJOA by regulating the HMGB1-RAGE/TLR4-NF-kB/AKT signalling pathway. This study revealed the potential of glycyrrhizin as a novel therapeutic drug to suppress TMJ cartilage degradation.

Chronic Pain Causes Peripheral and Central Responses in MIA-Induced TMJOA Rats.

Chronic pain is the predominant symptom that drives temporomandibular joint osteoarthritis (TMJOA) patients to seek medical care; however, currently used treatment modalities remain less effective. This study aimed to investigate chronic pain and the peripheral and central responses in monoiodoacetate (MIA)-induced TMJOA rats. First, the appropriate dose of MIA was determined based on pain behavior assessment in rats. Alterations of the condylar structure in TMJOA rats were evaluated by histological staining and micro-computed tomography (micro-CT). Second, the period of TMJOA chronic pain was further explored by assessing the numbers of glial fibrillary acidic protein (GFAP)-positive astrocytes and ionized calcium-binding adaptor molecule 1 (IBA-1)-positive microglia in the trigeminal spinal nucleus (TSN) and performing nonsteroidal anti-inflammatory drug (NSAID) efficacy experiments. Finally, the expression of neurofilament 200 (NF200), calcitonin gene-related peptide (CGRP), and isolectin B4 (IB4) in the trigeminal ganglion (TG) and TSN was assessed by immunofluorescence. MIA at 4 mg/kg was considered an appropriate dose. Gradual MIA-induced alterations of the condylar structure were correlated with temporomandibular joint (TMJ) pain. The numbers of GFAP- and IBA-1-positive cells were increased at 2, 3, and 4 weeks after MIA injection. NSAIDs failed to alleviate pain behavior 10 days after MIA injection. CGRP and IB4 levels in the TG and TSN were upregulated at 2 and 4 weeks. These results suggest that TMJOA-related chronic pain emerged 2 weeks after MIA injection. CGRP- and IB4-positive afferents in both the peripheral and central nervous systems may be involved in MIA-induced TMJOA-related chronic pain in rats.

LncRNA TUG1 compromised neuronal mitophagy in cerebral ischemia/reperfusion injury by targeting sirtuin 1.

BACKGROUND: Mitophagy protects against cerebral ischemia/reperfusion (CI/R)-induced neuronal apoptosis via mitochondrial clearance. Although taurine-upregulated gene 1 (lncRNA TUG1) has been proposed to be involved in the neuronal apoptosis evoked by CI/R, its specific role in mitophagy during the progression of CI/R injury remains unknown. METHODS: The CI/R rat model was established using middle cerebral artery occlusion/reperfusion (MCAO/R). Human neuroblastoma cell line SH-SY5Y was subjected to oxygen-glucose deprivation and reoxygenation (OGD/R). Ubiquitination assay, co-immunoprecipitation assay, RNA pull-down, and RNA immunoprecipitation were used to determine the interplay among TUG1, sirtuin 1 (SIRT1), and F-box and WD repeat domain-containing 7 (FBXW7). RESULTS: The upregulation of the TUG1 level and downregulation of the mitophagy were observed in both MCAO/R-treated rats and OGD/R-treated cells. The administration of si-TUG1 (a siRNA directed against TUG1) potentiated mitophagy and suppressed neuronal apoptosis in OGD/R-treated cells. However, the neuroprotective effect of si-TUG1 was reversed by mitophagy inhibitor or SIRT1 knockdown in vitro. Functionally, TUG1 enhanced FBXW7-mediated SIRT1 ubiquitination by upregulating FBXW7 expression. The overexpression of FBXW7 abrogated the si-TUG1-reinforced mitophagy by decreasing SIRT1 expression, thus aggravating neuronal apoptosis in the OGD/R+si-TUG1-treated cells. In rats with MCAO/R, the interference of TUG1 clearly decreased neuronal apoptosis, lessened the infarct volume, and relieved the neurological deficits. CONCLUSION: TUG1 knockdown promotes SIRT1-induced mitophagy by suppressing FBXW7-mediated SIRT1 degradation, thus relieving the neuronal apoptosis induced by CI/R injury. LncRNA TUG1 promotes neuronal apoptosis through inhibition of mitophagy. TUG1 decreased SIRT1 expression by promoting FBXW7-mediated SIRT1 ubiquitination. FBXW7/SIRT1 axis mediated the effect of TUG1 on OGD/R-induced neuronal apoptosis by regulating mitophagy.

The Regrowth of Mandibular Coronoid Process After Coronoidectomy: A Retrospective Analysis of 57 Cases.

PURPOSE: Coronoidectomy is carried out frequently as a part of the cranial-maxillofacial surgery procedure. There are few articles on the fate of coronoid process after coronoidectomy, except that several case reports mentioned that coronoid process had regenerated. This study aimed to radiographically access the anatomic outcomes of coronoid process and investigate which factors were associated with the outcomes after coronoidectomy. MATERIALS AND METHODS: A retrospective cohort study included patients undergoing coronoidectomy over a 7-year period. The primary outcome variable was the new coronoid process occurrence (yes/no). Secondary outcome variable was the type of the new coronoid process by evaluating its size, shape and position. Radiograph at 1-year postoperative visit was used to determine the outcomes. The predictor variables included age, sex, surgical purpose, surgical side, surgical approach and the maximal interincisal opening. Appropriate statistics were analyzed by SPSS version 22. χ2 test and binary logistic regression were used to assess the association between predictor factors and anatomic outcomes (P <.05). RESULTS: The study sample included 57 patients. In total, 96 coronoidectomies were performed. Seventy-four coronoid processes (77.1%) showed complete (n = 44, 45.8%), nonunion (n = 19, 19.8%) or partial (n = 11, 11.5%) regrowth, whereas no evidence of regeneration in 22 sites was observed radiographically at 1-year postoperative visit. Binary logistic regression showed that a young age (odds ratio 0.704; 95% confidence interval 0.562-0.882; P = .002) was significantly associated with regeneration of coronoid process. CONCLUSIONS: Coronoid process can mostly regenerate after coronoidectomy. A young age may contribute to regrowth of coronoid process.

New Meroterpenoid and Isocoumarins from the Fungus Talaromyces amestolkiae MST1-15 Collected from Coal Area.

Three new compounds including a meroterpenoid (1) and two isocoumarins (8 and 9), together with thirteen known compounds (2-7, 10-16) were isolated from the metabolites of Talaromyces amestolkiae MST1-15. Their structures were identified by a combination of spectroscopic analysis. The absolute configuration of compound 1 was elucidated on the basis of experimental and electronic circular dichroism calculation, and compounds 8 and 9 were determined by Mo2(OAc)4-induced circular dichroism experiments. Compounds 7-16 showed weak antibacterial activities against Stenotrophomonas maltophilia with MIC values ranging from 128 to 512 µg/mL (MICs of ceftriaxone sodium and levofloxacin were 128 and 0.25 µg/mL, respectively).

Standard orthodontic treatment after condylectomy for patients with active unilateral condylar hyperplasia.

INTRODUCTION: Unilateral condylar hyperplasia (UCH) is a progressive, nonneoplastic overgrowth of the condyle of the temporomandibular joint. For treating active UCH, a popular method combines orthognathic surgery with high condylectomy and orthodontic treatment. The goal of this study was to introduce a new method to correct asymmetry for active UCH. METHODS: Retrospectively, 47 patients with active UCH were divided into horizontal-type, vertical-type, and combined-type. All patients were treated with condylectomy plus postsurgery standard orthodontics (CPSO) with applied miniscrews implanted in infrazygomatic crest and hard palate to intrude affected side of maxillary molars and apply intermaxillary traction for contralateral molars. Cone-beam computed tomography was taken at presurgery, postsurgery, and the end of orthodontics (T3). RESULTS: In the vertical (n = 10) and combined (n = 28) types, deviation of the chin and the canting of the mandible and maxillary occlusal plane were significantly reduced at T3. A difference in the torque of bilateral maxillary first molar (U6) and bilateral mandibular first molar (L6) was significantly reduced at T3. The anterior, superior, and posterior joint spaces in the vertical-type and combined-type were significantly decreased at T3 compared with postsurgery. In contrast, in the horizontal-type group (n = 9), the deviation of the chin was corrected; however, the canting of the mandible and maxillary occlusal plane was significantly increased at T3 compared with presurgery. CONCLUSIONS: CPSO restored facial and occlusal symmetry for vertical-type and combined-type active UCH and returned affected-side condyle to the glenoid fossa. However, CPSO was not suitable for treating the horizontal-type UCH.

HMGB1 contributes to osteoarthritis of temporomandibular joint by inducing synovial angiogenesis.

BACKGROUND: High- mobility group 1 protein (HMGB1) is related with inflammation. Our former research reported that substantial HMGB1 situates at the synovium of osteoarthritis of temporomandibular joint (TMJOA) patients. OBJECTIVE: This study investigated whether HMGB1 promotes synovial angiogenesis of TMJOA and its underlying mechanism. METHODS: Human synovial fibroblasts were stimulated with HMGB1; the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible transcription factor-1α (HIF-1α) in these cells was explored by Western blotting, real-time PCR and immunofluorescent staining. The angiogenic capacity of these cells was assayed by tube formation and cell migration of human umbilical vein endothelial cells (HUVECs). The specific inhibitor against HMGB1, VEGF, Erk or JNK was added in these cells, respectively. Complete Freund's adjuvant (CFA)-induced TMJOA rats were produced. The changes in their synovium and synovial fluid were detected by immunofluorescent staining and ELISA. RESULTS: HMGB1 effectively up-regulated the production of VEGF and HIF-1α in TMJOA synovial fibroblasts through the activation of Erk and JNK. Conditioned medium from HMGB1-treated TMJOA synovial fibroblasts significantly promoted tube formation and migration in HUVECs, while attenuated those after the addition of certain inhibitor for VEGF. Furthermore, the specific inhibitor against HMGB1 vanished the neovascularisation and production of HIF-1α, VEGF and CD34 in the synovium of rat TMJOA induced by CFA injection. Additionally, this inhibitor led to the reduction of IL-6, IL-1ß and TNF-α in the synovial fluid of those rats. CONCLUSION: These findings disclose a key role for HMGB1 in governing synovial angiogenesis and as a therapeutic target against TMJOA.

TLR4 contributes to the damage of cartilage and subchondral bone in discectomy-induced TMJOA mice.

The abundance of inflammatory mediators in injured joint indicates innate immune reactions activated during temporomandibular joint osteoarthritis (TMJOA) progression. Toll-like receptor 4 (TLR4) can mediate innate immune reaction. Herein, we aimed to investigate the expression profile and effect of TLR4 in the cartilage and subchondral bone of the discectomy-induced TMJOA mice. The expression of TLR4 and NFκB p65 in the synovium of TMJOA patients was measured by immunohistochemistry, Western blotting and RT-PCR. H&E and Masson staining were utilized to assess the damage of cartilage and subchondral bone of the discectomy-induced TMJOA mice. A TLR4 inhibitor, TAK-242, was used to assess the effect of TLR4 in the cartilage and subchondral bone of the discectomy-induced TMJOA mice by Safranin O, micro-CT, immunofluorescence and immunohistochemistry. Western blotting was used to quantify the expression and effect of TLR4 in IL-1ß-induced chondrocytes. The expression of TLR4 and NFκB p65 was elevated in the synovium of TMJOA patients, compared with the normal synovium. TLR4 elevated in the damaged cartilage and subchondral bone of discectomy-induced TMJOA mice, and the rate of TLR4 expressing chondrocytes positively correlated with OA score. Intraperitoneal injections of TAK-242 ameliorate the extent of TMJOA. Furthermore, TLR4 promotes the expression of MyD88/NFκB, pro-inflammatory and catabolic mediators in cartilage of discectomy-induced TMJOA. Besides, TLR4 participates in the production of MyD88/NFκB, pro-inflammatory and catabolic mediators in IL-1ß-induced chondrocytes. TLR4 contributes to the damage of cartilage and subchondral bone in discectomy-induced TMJOA mice through activation of MyD88/NFκB and release of pro-inflammatory and catabolic mediators.