Knowledge mapping of disease-modifying therapy (DMT) in multiple sclerosis (MS): A bibliometrics analysis.

Background: Multiple sclerosis (MS) is a heterogeneous autoimmune disease, with a rapidly evolving body of literature on disease-modifying therapy (DMT) that urgently needs to be synthesized and regularized. Methods: The original material used for the analysis was obtained from the Web of Science Core Collection (WoSCC) in the Science Citation Index Expanded Edition (SCI-E). The data material was accessed through VOSviewer, Citespace, R package "Bibliometrix", and Scimago Graphica for data analysis and visualization. Among them, the clustering algorithm based on the Largest Likelihood Ratio (LLR) and the burst citation algorithm is the key. Results: As of November 6th, 2022, 4142 publications related to emerging disease-modifying therapies (e-DMT) for MS, 6521 publications related to traditional disease-modifying therapies (t-DMT) for MS, and 1793 publications in cross-cutting disease-modifying therapies (I-DMT) for MS were included in the analysis, respectively. Publications related to DMT in MS were analyzed descriptively (for three subjects: country, institution, and author) and predictively (for two subjects: keywords and references) separately according to three sections: e-DMT, t-DMT, and I-DMT. Topics that still have relevant reference output as of 2022 include the safety of Coronavirus disease 2019 (COVID-19) mRNA vaccination, therapeutic inertia (TI), cladribine tablets, autologous hematopoietic stem cell transplantation (aHSCT), progressive multiple sclerosis, and pediatric multiple sclerosis. Conclusion: The future research focus for MS DMT is the combination trial or cross-trial of various treatment methods to improve the development of individualized treatment plans for MS patients. The exact contents of the research frontiers are included but not limited to ocrelizumab, fingolimod and other monoclonal antibodies, fumaric acid ester, cladribine tablet, aHSCT, and other interventions of randomized controlled trials (RCTs); the impact of mRNA COVID-19 vaccination on MS patients; TI, patient adherence, and other medical management issues; and continued exploration of biomarkers for more accurate disease classification based on the existing clinical indication classification.

[Retracted] MicroRNA­509 acts as a tumor suppressor in tongue squamous cell carcinoma by targeting epidermal growth factor receptor.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell cell invasion assay data shown in Fig. 2C on p. 7248 and Fig. 3G on p. 7249 were strikingly similar to data in different form in other articles written by different authors at different research institutes, which had either already been published (some of which have now been retracted), or had been submitted for publication at around the same time. Owing to the fact that certain of the data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 7245­7252, 2017; DOI: 10.3892/mmr.2017.7531].

Responsiveness to Tocilizumab in Anti-Acetylcholine Receptor-Positive Generalized Myasthenia Gravis.

Tocilizumab, a humanized IL-6R monoclonal antibody, has been used in autoimmune diseases closely related to humoral immunity. This report aims to evaluate the efficacy and safety in patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG). We performed a prospective, open-label, single-arm study in patients with gMG in a 48-week follow-up. All patients were AChR+ and were given tocilizumab by intravenous infusion at a dose of 8 mg/kg at intervals of 4 weeks. The primary endpoint was mean change from baseline in quantitative MG (QMG) score at week 12. The secondary endpoints were mean changes from baseline in MG activities of daily living (MG-ADL) score, AChR-ab titers, and the dosage of oral prednisone at week 12. At week 48, QMG, MG-ADL, and the use of prednisone were also evaluated. Fourteen gMG patients were enrolled and all of them completed the study. Tocilizumab treatment started 8 (4-192) months after the onset of gMG. During tocilizumab treatment, the QMG score was significantly decreased from 15.5 (interqualile range, 9-26) at baseline to 4 (0-9) at week 12 (p < 0.001). The change of ADL was decreased from 14.5(11-19) at baseline to 4 (0-19) at week 12 (p < 0.001) and the change of AChR-ab titers from 15 (7.5-19) at baseline to 6.8 (11.6-4.3) at week 12 (p < 0.001). The dosage of prednisone decreased from baseline 60 (20-65) mg/d to 30 (30-50) mg/d at week 12 (p < 0.001). By the end of the study, the QMG score was 2 (0-7) and MG-ADL score was 1.5 (0-6). 12 (85.7%) patients achieved minimal manifestations. 4 (28.6%) patients were able to discontinue prednisone. No patients experienced exacerbation at the end of the study. No serious adverse events were observed during follow-up. Tocilizumab treatment was associated with a good clinical response and safety over a 48-week observation period, as evidenced by significant improvements in QMG and MG-ADL.

Improving the Quality of Dissimilar Al/Steel Butt-Lap Joint via Ultrasonic-Assisted Friction Stir Welding.

A dissimilar AA7075/Q235 butt-lap joint was fabricated via ultrasonic-assisted friction stir welding (UaFSW), and the characteristics of the UaFSW joint were investigated systematically. The acoustoplastic effect of the ultrasonic vibration led to the softening of the materials and enhanced the material flow during welding, decreasing the volume of welding defects in the nugget zone of the UaFSW joint. With the help of ultrasonic vibration, a smooth and thin intermetallic compounds (IMCs) layer could generate along the Al/steel interface at the top of nugget zone, which possibly consisted of Al5Fe2 and Al13Fe4 phases. However, the positive effects of the ultrasonic vibration were weakened at low temperatures; consequently, the IMCs layer became discontinuous at the bottom of the nugget zone and the welding defects also formed. The ultrasonic vibration accelerated the dynamic recrystallization and refined the microstructures in the nugget zone due to the increased strain rate and stored energy. As a result, the UaFSW joint exhibited a better mechanical performance in comparison to the FSW joint, and the increment in the peak tensile load/elongation was more than twice. In addition, the UaFSW joint failed in the nugget zone along with the Al/steel interface, and the fracture mode was a mixture of ductile and brittle.

Expression and clinical value of PD-L1 which is regulated by BRD4 in tongue squamous cell carcinoma.

The programmed cell death-ligand-1 (PD-L1) and bromodomain protein 4 (BRD4) are frequently overexpressed in cancer and have even been shown to act synergistically. The aim of this study was to determine their potential oncogenic role .in tongue squamous cell carcinoma (TSCC). We detected significantly higher expression levels of both PD-L1 and BRD4 in TSCC tissues compared to normal tissues (P ≤ .05). In addition, the high levels of PD-L1 were significantly associated with increased tumor lymphatic metastasis (P ≤ .05), tumor staging (P ≤ .01), as well as BRD4 expression (P ≤ .05). Genetic and pharmacological inhibition of BRD4 in TSCC cells not only reduced their growth rate but also PD-L1 levels (P ≤ .05), while overexpression of BRD4 upregulated PD-L1. Bioinformatics analysis showed that c-MYC and CDK9 were interactive partners of both BRD4 and PD-L1. While c-MYC clearly modulated the expression of PD-L1, as well as reversed the inhibitory effects of JQ1, no obvious association was observed between CDK9 and PD-L1. We report a novel regulatory axis consisting of BRD4, PD-L1, and c-MYC that likely drives TSCC progression, and is a potential prognostic marker and/or therapeutic target for TSCC.

BET bromodomain inhibitor JQ1 promotes immunogenic cell death in tongue squamous cell carcinoma.

Drug resistance substantially limits the curative capability of chemotherapy in head and neck cancers such as oral squamous cell carcinoma. Immunosuppression is considered a potential cause of drug resistance. A key discovery in the past decade is that chemotherapeutics can alter tumor cell immunogenicity via inducing release of damage-associated molecular patterns (DAMPs), including ecto-calreticulin (ecto-CALR), high mobility group box 1 (HMGB1) and ATP, causing tumor cells to die in a manner known as bona fide immunogenic apoptosis or immunogenic cell death (ICD). Intriguingly, JQ1 was found in this study to exhibit therapeutic potential in tongue squamous cell carcinoma (TSCC) by inducing ICD. JQ1 induced significant release of calreticulin (CALR), HMGB1 and ATP from Cal27 and SCC7 cells in vitro. Immature dendritic cells (Im-DCs) cocultured with JQ1-pretreated Cal27 cells exhibited significant upregulation of mature markers on their surface and an increase in the secretion of cytokines. In vivo experiments demonstrated that JQ1-pretreated dying SCC7 cells protected immunocompetent mice from rechallenge of SCC7 cells. Intravenous injection of JQ1 efficiently reduced tumor growth and increased tumor-infiltration of CD3+/CD8+ T cells in C3H mice.

JQ1 and PI3K inhibition synergistically reduce salivary adenoid cystic carcinoma malignancy by targeting the c-Myc and EGFR signaling pathways.

BACKGROUND: To investigate the therapeutic mechanism of the BRD4 inhibitor JQ1 in SACC-83 cells and explore strategies to enhance its therapeutic potential. MATERIAL AND METHODS: SACC-83 cells were used in the experiment. Immunohistochemistry was used to assess BRD4 expression in SACC tissues and corresponding adjacent non-tumor tissues. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay. Flow cytometry was used to quantitate apoptosis. Levels of cleaved caspase-3, BRD4, c-Myc, pEGFR (γ-1173), and EGFR were determined by quantitative real-time PCR and Western blot. To study the role of EGFR in JQ1 resistance, we generated EGFR knockdown SACC-83 cells by siRNA transfection. RESULTS: Our study revealed that BRD4 was overexpressed and could be a treatment target in SACC. The BRD4 inhibitor JQ1 markedly inhibited c-Myc expression in SACC-83 cells, which produced modest therapeutic effects. Nevertheless, the EGFR pathway was strongly activated following JQ1 treatment, which led to JQ1 resistance. Combined JQ1 and PI3K inhibitor treatment effectively increased the therapeutic potential by inhibiting the EGFR and c-Myc signaling pathways in SACC-83 cells. Moreover, EGFR knockdown sensitized SACC-83 cells to JQ1. CONCLUSION: These data demonstrate that EGFR and c-Myc signaling synergistically drive SACC progression. The JQ1 and PI3K inhibitor combination exhibited a strong synergistic effect by suppressing c-Myc and EGFR in SACC-83 cells, identifying a novel rational combinatorial treatment. Moreover, EGFR expression influences the sensitivity of SACC-83 cells to JQ1, which is useful for planning treatment.

Design, synthesis and biological evaluation of AKT inhibitors bearing a piperidin-4-yl appendant.

A series of AKT inhibitors possessing a piperidin-4-yl side chain was designed and synthesized. Some of them showed high AKT1 inhibitory activity and potent anti-proliferative effect on PC-3 prostate cancer cells in the preliminary screening. Further studies revealed the most potent compound, 10h, as a pan-AKT inhibitor. Compound 10h was able to inhibit the cellular phosphorylation of AKT effectively and induce apoptosis of PC-3 cells. It also showed high metabolic stability in human liver microsomes. Preclinical characterization of 10h, a promising lead AKT inhibitor, as a potential anti-prostate cancer therapeutic needs to be further investigated.

Development and in vitro evaluation of mucoadhesive patches of methotrexate for targeted delivery in oral cancer.

The present study focused on the development of a mucoadhesive patch of methotrexate (MTX) for targeted delivery in oral cancer. Initially, MTX-loaded liposomes were prepared using the thin film hydration method, and had a mean diameter of 105.7-137.4 nm and percentage entrapment efficiency of 54.6±3.5. These liposomes were cast in optimized mucoadhesive film. The film was characterized by its release pattern, thickness, weight and percentage swelling index and the sustained release profile of the optimized film was evaluated. The developed liposomes and liposomes cast in the film formulation were evaluated for cytotoxicity in HSC-3 cells using an MTT assay, and a significant decrease in the half maximal inhibitory concentration of MTX was identified with the MTX-entrapped liposomal film, M-LP-F7. The results of the mitochondria-dependent intrinsic pathway demonstrated that there was significant mitochondrial membrane potential disruption with M-LP-F7 compared with the plain drug. M-LP-F7 increased the rate of apoptosis in HSC-3 cells by almost 3-fold. Elevated levels of reactive oxygen species provided evidence that M-LP-F7 exerts a pro-oxidant effect in HSC-3 cells.

EGFR-mediated signaling pathway influences the sensitivity of oral squamous cell carcinoma to JQ1.

Inhibiting BRD4 has emerged as a promising anticancer strategy, and inhibitors such as JQ1 can suppress cell growth in oral squamous cell carcinoma (OSCC). However, the mechanism through which JQ1 exerts its anticancer activity has not been reported. Moreover, JQ1 does not markedly inhibit proliferation and increase apoptosis in OSCC when used as a monotherapy. Herein, we explore the mechanism of JQ1 in OSCC and probe ways to increase its therapeutic potential. In this study, we used two cell lines, Cal27, and Scc25. We found that BRD4 was highly expressed in OSCC tissues when compared with adjacent non-tumor tissues, and JQ1 worked through the EGFR-mediated signaling pathway in tumor cells. Furthermore, we demonstrated that JQ1 induced an increased treatment effect in vitro and in vivo when combined with a PI3K inhibitor. Interestingly, subsequent mechanistic analyses indicated that further suppressing EGFR and BRD4 expression was instrumental to this functional synergism. Moreover, we found that upregulating EGFR expression by EGF stimulation protected cells treated with JQ1 from apoptosis, while knockdown of EGFR before addition of JQ1 successfully mimicked the combination treatment results. In summary, our findings revealed that JQ1 can act by inhibiting the EGFR-mediated signaling pathway, and EGFR expression influences the sensitivity of OSCC to JQ1. Regarding clinical use, this study demonstrates that BRD4 is a novel therapeutic target and EGFR can be used as a biomarker to identify the most appropriate anti-BRD4 treatment strategy in OSCC.

MicroRNA­509 acts as a tumor suppressor in tongue squamous cell carcinoma by targeting epidermal growth factor receptor.

Tongue squamous cell carcinoma (TSCC) is the most frequent type of oral carcinoma, and is characterized by high metastatic and growth capabilities. Previous studies have demonstrated that aberrantly expressed cancer­associated microRNAs (miRs) may be associated with tumorigenesis and tumor development in various types of cancer, including TSCC. miR­509 has been identified as a critical regulator in tumorigenesis and tumor development, via its tumor­suppressing actions in several types of human cancer. In the present study, miR­509 expression in TSCC tissues and cell lines was determined by reverse transcription­quantitative polymerase chain reaction. The effects of miR­509 on TSCC cell proliferation and invasion were evaluated via MTT and invasion assays, respectively. In addition, the direct target of miR­509 in TSCC was investigated. The present study demonstrated that miR­509 expression was downregulated in TSCC tissue samples and cell lines, whereas its ectopic expression suppressed TSCC cell proliferation and invasion in vitro. In addition, epidermal growth factor receptor (EGFR) was identified as a direct target gene of miR­509 in TSCC cells. EGFR downregulation was demonstrated to suppress the proliferation and invasion of TSCC cells, similar to miR­509 overexpression. Furthermore, EGFR was significantly upregulated in TSCC tissues, and the levels of miR­509 were revealed to be negatively correlated with EGFR expression in TSCC tissues. Following transfection with miR­509 mimics, signaling pathways downstream of EGFR appeared to be suppressed, as phosphorylated (p)­extracellular signal­regulated kinase and p­Akt were downregulated in TSCC cells. In conclusion, the results of the present study suggested that miR­509 may inhibit the proliferation and invasion of TSCC cells via directly targeting EGFR, thus suggesting that the miR­509/EGFR axis may have potential as a novel therapeutic target for the development of a treatment for patients with TSCC.

Generation and characterization of a human oral squamous carcinoma cell line SCC-9 with CRISPR/Cas9-mediated deletion of the p75 neurotrophin receptor.

OBJECTIVE: To investigate the importance of the p75 neurotrophin receptor (p75NTR) in human tongue squamous carcinoma cells, we exploited the CRISPR/Cas9 technology to establish a p75NTR-knockout SCC-9 cell line and to explore the effect on biological functions. MATERIALS AND METHODS: The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonuclease (Cas9) system was used to generate genomic deletion mutants of p75NTR in the tongue squamous carcinoma cell lines SCC-9. Single-guide RNA (sgRNA) sequences were designed to target the p75NTR genomic sequence and were cloned into plasmid pGK1.1. The linearized vector was electroporated into SCC-9 cells and p75NTR deletion was confirmed using Cruiser™ enzyme digestion and PCR amplification. SCC-9 clones with successful deletion of p75NTR were identified and verified by sequencing and selected for functional testing in cell proliferation, invasion, migration, and colony-forming assays. RESULTS: Compared with control cells, p75NTR-knockout SCC-9 cells showed significantly diminished abilities to proliferate, invade, migrate, and form colonies, indicating a reduction in pro-tumorigenic behavior. CONCLUSION: These data demonstrate, first, that the CRISPR/Cas9 system is a simplified method for generating p75NTR knockouts with relatively high efficiency, and second, that deletion of p75NTR suppresses several tumor-promoting properties of SCC-9 cells, suggesting that p75NTR is a potential target for the development of novel therapies for tongue cancer.

BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma.

BACKGROUND: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). METHODS: The human normal epithelial cells and SACC cells (ACC-LM and ACC-83) were treated with JQ1 at concentrations of 0, 0.1, 0.5 or 1 µM. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis and cell cycle distribution was evaluated by Flow cytometry. Immunofluorescence staining was used to examine the expression of BRD4 in SACC cells. The quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were performed to examine messenger RNA (mRNA) and protein levels in SACC cells. Wound-healing assay and transwell assay were used to evaluate the activities of migration and invasion of SACC cells. RESULTS: JQ1 exhibits no adverse effects on proliferation, cell cycle and cell apoptosis of the normal human epithelial cells, while suppressed proliferation and cell cycle, and induced apoptosis of SACC cells, down-regulated the mRNA and protein levels of BRD4 in SACC cells, meanwhile reduced protein expressions of c-myc and BCL-2, two known target genes of BRD4. Moreover, JQ1 inhibited SACC cell migration and invasion by regulating key epithelial-mesenchymal transition (EMT) characteristics including E-cadherin, Vimentin and Twist. CONCLUSIONS: BRD4 is an important transcription factor in SACC and BRD4 inhibition by JQ1 may be a new strategy for SACC treatment.

Design, synthesis, and evaluation of novel Akt1 inhibitors based on an indole scaffold.

A new series of potential Akt1 inhibitors with indole scaffold were designed and synthesized. The antiproliferative activity against PC-3 cell line and enzyme inhibitory activity against Akt1 were evaluated. Among them, some compounds showed much more potent antiproliferative activity and stronger Akt1 inhibitory activity compared to the positive control of GSK690693. In particular, compound 19b exhibited the most potent inhibitory activity against Akt1 with inhibition rate of 70.3% at a concentration of 10 nm. Furthermore, compound 19b could dose dependently reduce the phosphorylation of the downstream GSK3ß protein in the PC-3 cell line and displayed fivefold higher antiproliferative activity against PC-3 cell line with IC50 value of 3.1 ± 0.1 µm than positive control (15.5 ± 0.4 µm). Herein, compound 19b may serve as a promising lead for further optimization and development of novel Akt1 inhibitors based on an indole scaffold.

p75 neurotrophin receptor: A potential surface marker of tongue squamous cell carcinoma stem cells.

The present study detected p75 neurotrophin receptor (p75NTR) expression in tongue squamous cell carcinoma (TSCC) cell lines, in order to define the biological properties of p75NTR+ cells and to confirm the use of p75NTR+ as a surface marker for TSCC stem cells. p75NTR+ cells were separated from Tca­8113 and CAL­27 TSCC cells by fluorescence­activated cell sorting. Colony formation, MTT and scratch assays, and a tumorigenicity analysis were performed to measure self-renewal and proliferation, multidirectional differentiation, and tumorigenicity of p75NTR+ cells. p75NTR+ cells comprised 3.1 and 1.9% of Tca­8113 and CAL­27 cells (mean of three experiments), respectively, and were more able to form colonies compared with non­sorted cells (P<0.01). In addition, the proportion of p75NTR+ cells generated from monoclonal p75NTR+ cells decreased to 14.5 (Tca­8113) and 5.8% (CAL­27) of cells within 2 weeks, thus suggesting that p75NTR+ cells are able to generate p75NTR+ and p75NTR­ cells. Furthermore, p75NTR+ cells exhibited increased proliferation, as evidenced by MTT assay (P<0.01) and had greater metastatic ability according to the scratch assay (P<0.01), compared with non­sorted cells. p75NTR+ cells also exhibited a greater tumorigenic capacity compared with non­sorted cells. In conclusion, p75NTR+ cells isolated from TSCC cell lines possess the characteristics of cancer stem cells; therefore, p75NTR may be considered a useful surface marker for the identification of TSCC stem cells.

BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma

BACKGROUND: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). METHODS: The human normal epithelial cells and SACC cells (ACC-LM and ACC-83) were treated with JQ1 at concentrations of 0, 0.1, 0.5 or 1 µM. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis and cell cycle distribution was evaluated by Flow cytometry. Immunofluorescence staining was used to examine the expression of BRD4 in SACC cells. The quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were performed to examine messenger RNA (mRNA) and protein levels in SACC cells. Wound- healing assay and transwell assay were used to evaluate the activities of migration and invasion of SACC cells. RESULTS: JQ1 exhibits no adverse effects on proliferation, cell cycle and cell apoptosis of the normal human epithelial cells, while suppressed proliferation and cell cycle, and induced apoptosis of SACC cells, down-regulated the mRNA and protein levels of BRD4 in SACC cells, meanwhile reduced protein expressions of c-myc and BCL-2, two known target genes of BRD4. Moreover, JQ1 inhibited SACC cell migration and invasion by regulating key epithelial-mesenchymal transition (EMT) characteristics including E-cadherin, Vimentin and Twist. CONCLUSIONS: BRD4 is an important transcription factor in SACC and BRD4 inhibition by JQ1 may be a new strategy for SACC treatment.

JQ1, a small molecule inhibitor of BRD4, suppresses cell growth and invasion in oral squamous cell carcinoma.

The present study aimed to evaluate whether bromodomain 4 (BRD4) is expressed in Cal27 cells and to assess the effect of JQ1 on cell proliferation, apoptosis, invasion and BRD4, C-Myc and Twist expression in Cal27 cells. Immunofluorescence staining was used to determine whether BRD4 was expressed in Cal27 cells. Cell viability and proliferation were evaluated using CCK-8 assay. Flow cytometry was used to determine the apoptosis and cell cycle distribution. The cell invasion was evaluated using Transwell plate. The expression levels of BRD4, C-Myc and Twist were determined by quantitative RT-PCR (qRT-PCR) and western blotting. BRD4 was highly expressed in Cal27 cells. JQ1 inhibited cell proliferation, induced cell apoptosis, induced cell cycle arrest, and inhibited cell invasion. Gene and protein expression levels of BRD4, C-Myc and Twist were downregulated in cells treated with JQ1. JQ1 inhibited Cal27 cell growth and invasion, and downregulated expression of several oncogenes. JQ1 may be a new drug for oral squamous cell carcinoma treatment.

Development of a reactive oxygen species (ROS)-responsive nanoplatform for targeted oral cancer therapy.

In this study, for effective oral cancer therapy, a new targeted and ROS-triggered drug delivery nanoplatform was developed from the RGD-PEG-TK-PLGA polymer, in which the ROS-responsive TK containing linker was connected with PEG and PLGA. RGD in the drug delivery system (DDS) presented here was used to target cancer cells. This new nanoplatform shows high stability, good targeting ability, excellent ROS sensitivity and excellent biocompatibility. Loaded with DOX and alpha-TOS, the formulated nanoparticles (NPs) demonstrate much better cellular uptake efficiency and higher inhibition performance towards the oral tongue Cal27 cancer cell line. In vivo anticancer evaluation indicates that DOX and alpha-TOS loaded RGD-PEG-TK-PLGA NPs have no toxicity to mice and showed significantly improved therapeutic efficacy against tumors. Therefore, this polymeric NP platform presents great potential as a new DDS for oral cancer chemotherapy.

Effects of GPNMB on proliferation and odontoblastic differentiation of human dental pulp cells.

Glycoprotein (transmembrane) nonmetastatic melanoma protein b (GPNMB) plays crucial roles in odontogenesis. However, the role of GPNMB in human dental pulp cells (hDPCs) is still unclear. Therefore, in this study, we investigated the expression and function of the GPNMB in odontoblastic differentiation of hDPCs. Cells were cultured in odontoblast differentiation-inducing medium; the expression of the GPNMB was assessed by reverse transcriptase polymerase chain reaction and Western blot analysis. We performed gene knockdown of GPNMB in hDPCs using lentivirus-mediated small interfering RNA (siRNA)-GPNMB. The proliferation of cells was measured by the MTT assay, and the differentiation of cells was detected with alkaline phosphatase (ALP) activity assay, qRT-PCR and Western blot were used to determine the expression levels of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1). The expression level of GPNMB was significantly increased during odontoblastic differentiation of hDPCs. Suppression of GPNMB expression by siRNA-GPNMB obviously promoted the proliferation of hDPCs. Furthermore, siRNA-GPNMB significantly inhibited the activity of ALP and expression levels of DSPP and DMP-1 during odontoblastic differentiation of hDPCs. Our results show that GPNMB plays an important role in regulating the expression of key pluripotency genes in hDPCs and modifying odontogenic differentiation.

Magnetic resonance imaging of temporomandibular joint: morphometric study of asymptomatic volunteers.

BACKGROUND: The aims of this study were to determine the best suited magnetic resonance imaging scanning plane, scanning sequence, and imaging modality for the evaluation of the temporomandibular joint (TMJ) and quantitatively assess the relationship of articular disk position to condyle position. METHODS: One hundred four TMJs in 52 symptom-free heads were examined by magnetic resonance imaging. The best scanning plane, scanning sequence, and scanning parameter were determined according to the imaging time and image quality. Bilateral symmetry of the articular disk and mandibular condyle was measured by using the automatic measurement of 3.0-T GE Excite Signa MR scanner. RESULTS: Fast spin-echo sequence, oblique sagittal imaging plane, and proton density imaging were the best suited scanning sequence, scanning planes, and imaging modality, respectively. The thicknesses of the anterior and posterior bands and for the intermediate zone were not statistically different for both sides. The posterior band of the disk was found to originate in an area adjacent to the 12-o'clock position of the condyle (± 5 degrees), whereas the anterior band of the disk originated adjacent to 1-o'clock position (28 ± 6 degrees). The anteroposterior diameter and mediolateral diameter of the condylar processes were not statistically different for both sides. The axial condylar angle between the plane of the greatest mediolateral diameter of the condylar processes and the midsagittal plane were also not statistically different for both sides. CONCLUSIONS: The magnetic resonance images can depict clearly major regional anatomic structures and position in the TMJ, which can be used in the early diagnosis for the TMJ disorder.