Potential Roles of Bone Morphogenetic Protein 9 in the Odontogenic Differentiation of Dental Pulp Cells

IntroductionThe differentiation of dental pulp cells (DPCs) plays an important role in the repair of dental pulp injury. Bone morphogenetic protein 9 (BMP9) is one of the most effective BMPs to induce the differentiation of stem cells. However, the role of BMP9 in promoting the odontogenic differentiation of DPCs and dentinogenesis is worth knowing.MethodsFluorescence in situ hybridization and immunohistochemistry staining were performed to detect the BMP9 expression in human dental pulp. BMP9 was overexpressed in human DPCs (hDPCs), and the mineralization of hDPCs was tested by alkaline phosphatase staining and alizarin red staining. The expression of odontogenic differentiation-related genes was examined by quantitative real-time polymerase chain reaction and western blotting. The subcutaneous transplantation experiment was performed to test the odonto-induction ability of BMP9 in vivo. The rat direct pulp-capping experiment was performed to test the function of BMP9 in promoting dentin formation.ResultsBMP9 showed an increased expression in odontoblast layer at both the mRNA and protein levels. BMP9 enhanced the mineralization and induced the expression of odontogenic differentiation-related genes in hDPCs. More mineralized nodules, and increased expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP1) were detected in the beta-tricalcium phosphate scaffold/cells composites of BMP9 group compared with the control group. Meanwhile, there was thicker reparative dentin formation in the BMP9 group in the rat pulp exposure experiment.ConclusionsBMP9 participates in the process of DPC differentiation and promotes DPC mineralization and dentinogenesis. BMP9 might be a potential therapeutic target in the repair of dental pulp injury.     

Effect of enhancer of zeste homolog 2 inhibitor GSK126 on the proliferation and apoptosis of tongue squamous cell carcinoma

目的 观察zeste基因增强子同源物2（EZH2）抑制剂GSK126对人舌鳞状细胞癌细胞体外增殖与凋亡的影响,并探讨其相关机制,为舌鳞状细胞癌的临床治疗提供新思路。方法 将不同浓度的GSK126作用于舌鳞状细胞癌CAL-27细胞,通过甲基噻唑基四唑（MTT）、克隆形成、5-乙炔基-2’脱氧尿嘧啶核苷（EdU）荧光染色实验检测药物对细胞增殖能力的影响;采用Hoechst33342荧光染色、JC-1法观察细胞凋亡情况;采用Western blot法检测CAL-27细胞内相关蛋白细胞外调节蛋白激酶（ERK）、磷酸化的细胞外调节蛋白激酶（p-ERK）、Bax、Bcl-2、Cleaved caspase-9的表达水平。结果 GSK126能抑制CAL-27细胞增殖并对细胞凋亡有促进作用。GSK126能下调细胞内p-ERK、Bcl-2的表达水平,同时可增加Bax、Cleaved caspase-9的表达（P<0.05）。结论 GSK126可抑制舌鳞状细胞癌CAL-27细胞的增殖,并且能促进其凋亡,其机制可能与抑制MEK/ERK信号通路以及激活Bax/Bcl-2通路有关。     

Biomechanical analysis of occlusal modes on the periodontal ligament while orthodontic force applied

Clinical Oral Investigations - The study objective was to investigate four common occlusal modes by using the finite element (FE) method and to conduct a biomechanical analysis of the periodontal...     

Metabolic syndrome and masticatory hypofunction: a cross-sectional study

Odontology - The objective of this paper is to clarify the rate of abdominal obesity (AO), waist-to-height ratio (WHtR), metabolic syndrome (MetS) and determine the relationship with the...     

DNA Methylation Profiling Revealed Promoter Hypermethylation-induced Silencing of p16, DDAH2 and DUSP1 in Primary Oral Squamous Cell Carcinoma

Background: Hypermethylation in promoter regions of genes might lead to altered gene functions and result in malignant cellular transformation. Thus, biomarker identification for hypermethylated genes would be very useful for early diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). The objectives of this study were to screen and validate differentially hypermethylated genes in OSCC and correlate the hypermethylation-induced genes with demographic, clinocopathological characteristics and survival rate of OSCC.Methods: DNA methylation profiling was utilized to screen the differentially hypermethylated genes in OSCC. Three selected differentially-hypermethylated genes of p16, DDAH2 and DUSP1 were further validated for methylation status and protein expression. The correlation between demographic, clinicopathological characteristics, and survival rate of OSCC patients with hypermethylation of p16, DDAH2 and DUSP1 genes were analysed in the study.Results: Methylation profiling demonstrated 33 promoter hypermethylated genes in OSCC. The differentially-hypermethylated genes of p16, DDAH2 and DUSP1 revealed positivity of 78%, 80% and 88% in methylation-specific polymerase chain reaction and 24% and 22% of immunoreactivity in DDAH2 and DUSP1 genes, respectively. Promoter hypermethylation of p16 gene was found significantly associated with tumour site of buccal, gum, tongue and lip (P=0.001). In addition, DDAH2 methylation level was correlated significantly with patients'' age (P=0.050). In this study, overall five-year survival rate was 38.1% for OSCC patients and was influenced by sex difference.Conclusions: The study has identified 33 promoter hypermethylated genes that were significantly silenced in OSCC, which might be involved in an important mechanism in oral carcinogenesis. Our approaches revealed signature candidates of differentially hypermethylated genes of DDAH2 and DUSP1 which can be further developed as potential biomarkers for OSCC as diagnostic, prognostic and therapeutic targets in the future.     

Prevention of allergic airway hyperresponsiveness and remodeling in mice by <Emphasis Type="Italic">Astragaliradix</Emphasis> Antiasthmatic decoction

Background

Astragali radix Antiasthmatic Decoction (AAD), a traditional Chinese medication, is found effective in treating allergic diseases and chronic cough. The purpose of this study is to determine whether this medication could suppress allergen-induced airway hyperresponsiveness (AHR) and remodeling in mice, and its possible mechanisms.

Methods

A mouse model of chronic asthma was used to investigate the effects of AAD on the airway lesions. Mice were sensitized and challenged with ovalbumin (OVA), and the extent of AHR and airway remodeling were characterized. Cells and cytokines in the bronchoalveolar lavage fluid (BALF) were examined.

Results

AAD treatment effectively decreased OVA-induced AHR, eosinophilic airway inflammation, and collagen deposition around the airway. It significantly reduced the levels of IL-13 and TGF-β1, but exerted inconsiderable effect on INF-γ and IL-10.

Conclusions

AAD greatly improves the symptoms of allergic airway remodeling probably through inhibition of Th2 cytokines and TGF-β1.

     

Simple weak-acid derivatives of paclitaxel for remote loading into liposomes and improved therapeutic effects

Liposomes are among the most successful nanocarriers; several products have been marketed, all of which were prepared by active loading methods. However, poorly water-soluble drugs without ionizable groups are usually incorporated into the lipid bi-layer of liposomes by passive loading methods, with serious drug leakage during blood circulation. Furthermore, there have been few improvements in their anti-cancer activity and safety. Herein, we designed and synthesized three weak-acid modified paclitaxel (PTX) derivatives with a one-step reaction for the remote loading of liposomal formulations. By comparison, PTX-succinic acid liposomes (PTX-SA LPs) exhibited the highest encapsulation efficiency (97.2 ± 1.8%) and drug loading (8.84 ± 0.16%); meanwhile, there was almost no change in their particle size or zeta potential within one month. Furthermore, compared with Taxol®, the PTX-SA LPs showed a 4.35-fold prolonged half-time, enhanced tumor accumulation, and an increased maximum tolerated dose (MTD) of more than 30 mg kg⁻¹. As a result, the PTX-SA LPs displayed significantly improved in vivo anti-cancer efficacy in comparison with Taxol®. Therefore, weak-acid modification is proved to be a simple and effective method to achieve remote loading and high encapsulation efficiency of poorly soluble drugs, showing great potential for clinical application.

A remote loading liposomal formulation of weak-acid paclitaxel derivative with high encapsulation efficiency and high drug loading, improved therapeutic efficiency and negligible toxicity.     

Self-assembly of photoresponsive azo-containing phospholipids with a polar group as the tail

Vesicles or micelles prepared from amphiphiles with azobenzene (Az) moieties and long alkyl chains have attracted much attention in drug delivery systems. To induce release behavior from smart carriers via trans–cis photoisomerization of the Az groups, UV light exposure is typically used, but it can damage DNA and hardly penetrates cells. In this paper, Az-containing phospholipids without long alkyl tails were designed and synthesized; in these compounds, the end group of the Az moiety was substituted with a –NO₂ and –OCH₃ group (abbreviated N6 and M6, respectively). N6 self-assembled into H-aggregates with an interdigitated bilayered structure in water through the antiparallel orientation due to π–π interactions of the Az group, the attractive van der Waals forces, and the interactions and bending behavior of the phosphocholine groups. Vesicles showing visible light stimuli-responsive behavior were obtained by mixing N6 and M6, and the release of encapsulated calcein was triggered by visible light.

A mixture of a nitro- and methoxy-substituted azo-containing phospholipids without long alkyl tails formed vesicles showing visible light stimuli-responsive behavior. Release of encapsulated calcein from the vesicles was triggered by visible light.