Wei Qin

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (15)29.98 Total impact

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    ABSTRACT: The inflammasome has been determined to play an important role in inflammatory diseases in recent years. Absent in melanoma 2 (AIM2), an inflammasome that recognizes cytoplasmic DNA, has recently been identified as a critical regulator of immune responses. In this study, we explored whether AIM2 was expressed in human dental pulp and defined the role of AIM2 in regulating interleukin (IL)-1β secretion. We demonstrated that AIM2 was only detected in the odontoblast layer of healthy dental pulp, whereas strong expression was observed in inflamed dental pulp. Stimulation with interferon gamma (IFN-γ) and cytoplasmic DNA significantly activated the AIM2 inflammasome and increased IL-1β secretion in human dental pulp cells (HDPCs) in a time- and dose-dependent manner. Moreover, the knockdown of AIM2 downregulated both cleaved-caspase-1 expression and IL-1β release in HDPCs. These results suggest that AIM2 expressed in human dental pulp plays an important role in the immune defense by activating the inflammasome signaling pathway.
    Inflammation 07/2014; · 2.46 Impact Factor
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    ABSTRACT: Abstract Bone morphogenetic protein-2 (BMP-2) is a multi-functional growth factor belonging to the transforming growth factor β (TGF-β) superfamily that has a broad range of activities that affect many different cell types. BMP-2 induces odontoblastic differentiation of human dental pulp cells (DPCs), but the underlying mechanism remains unclear. In the present study, we investigated the potential role of the JNK MAPK pathway in BMP-2-induced odontoblastic differentiation of DPCs. The levels of phosphorylated and unphosphorylated JNK MAPK were quantified by Western blot analysis following treatment with BMP-2 and the JNK inhibitor SP600125. The role of JNK MAPK in the BMP-2-induced odontoblastic differentiation of DPCs was determined by measuring alkaline phosphatase (ALP) activity and by examining the expression of odontoblastic markers using quantitative real-time polymerase chain reaction analysis. The effect of JNK MAPK silencing on odontoblastic differentiation was also investigated. BMP-2 upregulated the phosphorylation of JNK in DPCs in a dose- and time-dependent manner. Early markers of odontoblastic differentiation, including ALP activity, osteopontin (OPN), and dentin matrix protein-1 (DMP-1), were not inhibited by the JNK inhibitor. However, the JNK inhibitor SP600125 significantly inhibited late-stage differentiation of odontoblasts, including the gene expression of osteocalcin (OCN), dentin sialophosphoprotein (DSPP), and bone sialoprotein (BSP), and also reduced the formation of mineralized nodules in BMP-2-treated DPCs. Consistent with this observation, silencing of JNK MAPK also decreased late-stage odontoblastic differentiation. Taken together, these findings suggest that JNK activity is required for late-stage odontoblastic differentiation induced by BMP-2.
    Connective tissue research 01/2014; · 1.55 Impact Factor
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    ABSTRACT: Background/purpose Noncarious cervical lesions (NCCLs) are among the most frequent conditions requiring resin restorations. However, the major shortcoming of these restorations is limited longevity. The purpose of this study was to compare the clinical performance of self-etching (SE) adhesives with or without selective enamel etching in NCCLs. Materials and methods An initial literature search, with strict inclusion and exclusion criteria, was conducted in MEDLINE, Web of Science, the Wiley Online database, and the Cochrane Controlled Trials Center. Eight trials were included. Restoration retention, prevalence of marginal defects, and marginal discoloration were evaluated. Data were analyzed using the Mantel–Haenszel method with 95% confidence intervals. Results Results demonstrated that fewer marginal defects (P = 0.0001) and discoloration (P = 0.008) were observed with the selective enamel etching approach. The risk ratio (RR) values of the selective etching group and the nonselective etching group for marginal defects and discoloration were 0.58 (0.44, 0.77) and 0.48 (0.28, 0.83), respectively. For restoration retention, the differences between the two groups were not significant (P = 0.44). The RR values of the selective etching group and the nonselective etching group for restoration retention were 1.01 (0.98, 1.04) and 1.02 (0.96, 1.08), according to a fixed-effects model at 2- and 5-year observation time, respectively. Conclusion Prior enamel etching resulted in fewer marginal defects and marginal discoloration, compared with using the SE approach alone. For restoration retention, the differences between the two groups were not significant. Additional longer follow ups and large-scale investigations are expected to assess possible advantages of selective enamel etching in NCCL restorations.
    Journal of Dental Sciences. 01/2014;
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    ABSTRACT: Phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin inhibitor (mTOR) pathway is often constitutively activated in human tumor cells and thus has been considered as a promising drug target. To ascertain a therapeutical approach of nasopharyngeal carcinoma (NPC), we hypothesized NVP-BEZ235, a novel and potent imidazo[4,5-c] quinolone derivative, that dually inhibits both PI3K and mTOR kinases activities, had antitumor activity in NPC. Expectedly, we found that NVP-BEZ235 selectively inhibited proliferation of NPC cells rather than normal nasopharyngeal cells using MTT assay. In NPC cell lines, with the extended exposure, NVP-BEZ235 selectively inhibited proliferation of NPC cells harboring PIK3CA mutation, compared to cells with wild-type PIK3CA. Furthermore, exposure of NPC cells to NVP-BEZ235 resulted in G1 growth arrest by Propidium iodide uptake assay, reduction of cyclin D1and CDK4, and increased levels of P27 and P21 by Western blotting, but negligible apoptosis. Moreover, we found that cisplatin (CDDP) activated PI3K/AKT and mTORC1 pathways and NVP-BEZ235 alleviated the activation by CDDP through dually targeting PI3K and mTOR kinases. Also, NVP-BEZ235 combining with CDDP synergistically inhibited proliferation and induced apoptosis in NPC cells. In CNE2 and HONE1 nude mice xenograft models, orally NVP-BEZ235 efficiently attenuated tumor growth with no obvious toxicity. In combination with NVP-BEZ235 and CDDP, there was dramatic synergy in shrinking tumor volumes and inducing apoptosis through increasing Noxa, Bax and decreasing Mcl-1, Bcl-2. Based on the above results, NVP-BEZ235, which has entered phase I/II clinical trials in patients with advanced solid tumors, has a potential as a monotherapy or in combination with CDDP for NPC treatment.
    PLoS ONE 01/2013; 8(3):e59879. · 3.73 Impact Factor
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    ABSTRACT: One of the best-characterized Nod-like receptor (NLR) family members is pyrin domain containing 3 (NLRP3). Intracellular NLRP3 is the most versatile innate immune receptor. On activation, NLRP3 assembles into a multiprotein complex, termed an inflammasome, which regulates the secretion and bioactivity of interleukin-1 family cytokines. NLRP3 has broad specificity for mediating an immune response to a wide range of microbial stimuli or danger signals. Therefore, we hypothesize that NLRP3 plays an essential role in the detection of bacterial pathogens and the initiation of inflammation within the dental pulp. Thus, the aim of this study was to evaluate the expression of NLRP3 in normal human dental pulp cells (HDPCs) and pulp tissues. Pulp tissues were collected from freshly extracted human third molars, and HDPCs were prepared from the explants of normal dental pulp tissues. Reverse transcription-polymerase chain reaction and Western blotting were performed to detect the levels of NLRP3 mRNA and protein, respectively. In addition, immunohistochemical staining was used to determine the distribution of NLRP3 in pulp tissues. Normal human dental pulp tissues displayed high levels of NLRP3 mRNA and protein. NLRP3 proteins were principally expressed in odontoblasts and some pulp vascular endothelial cells. Moreover, HDPCs also expressed NLRP3 but at a relatively low level in comparison with that of dental pulp tissues. The expression of NLRP3 in HDPCs and pulp tissues suggests that NLRP3-mediated signaling pathways may play an important role in dental immune defense.
    Journal of endodontics 12/2012; 38(12):1592-7. · 2.95 Impact Factor
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    ABSTRACT: OBJECTIVE: The purpose of this double-blind, randomised trial was to compare the clinical performance of a hybrid composite (Clearfil AP-X, Kuraray, Tokyo) and a nanocomposite (Filtek Z350, 3M ESPE, St. Paul, MN) over a period of 2 years in non-carious class V lesions using a modified US Public Health Service (USPHS) system. METHODS: Forty-six patients with at least one pair of equivalent non-carious cervical lesions under occlusion and a mean age of 44.1 years (range 27-66 years; median 45 years) were enrolled in this study. A total of 116 restorations (58 with each material) were placed according to manufacturer's instructions by two calibrated operators. The restorations were evaluated at baseline and at 6, 12 and 24 months after placement using the USPHS criteria for retention, colour match, marginal discolouration, marginal adaptation, anatomic form, surface texture and secondary caries. Statistical analysis was conducted using the Cochran and the McNemar tests at a significance level of 5 % (P < 0.05). RESULTS: No surface texture changes or secondary caries were detected in association with any restorations. The retention rates for Clearfil AP-X (100 %) and for Filtek Z350 (91.38 %) did not differ significantly (P > 0.05). Two Z350 restorations were completely lost after 2 years. No significant differences were observed in the colour match, marginal discolouration, marginal adaptation or anatomic form. CONCLUSIONS: There were no significant differences in the clinical performances between the materials. CLINICAL RELEVANCE: Both restorative materials exhibited acceptable clinical performance in class V non-carious lesions 2 years post-restoration.
    Clinical Oral Investigations 07/2012; · 2.20 Impact Factor
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    ABSTRACT: To investigate whether the p38α mitogen-activated protein kinases (MAPK) is involved in bone morphogenetic protein (BMP)-2-induced odontoblastic differentiation of human dental pulp cells (HDPCs). Recombinant retrovirus encoding shRNA against p38α MAPK was constructed to investigate the role of p38α MAPK on BMP-2-induced odontoblastic differentiation of HDPCs. HDPCs were transfected with retrovirus expressing sh-p38α. Activation of p38α MAPK was detected by Western blot. The effects of p38α MAPK on BMP-2-induced odontoblastic differentiation of HDPCs were measured by alkaline phosphatase (ALP) activity, and the expression of odontoblastic markers was identified by quantitative real-time polymerase chain reaction analysis. The effect of SD-282, a p38a-specific inhibitor, on BMP-2-induced odontoblastic differentiation was also investigated. BMP-2 dose- and time-dependently upregulated phosphorylation of p38α of HDPCs. Compared with BMP-2-treatment group, gene knock-down of p38α MAPK significantly inhibited ALP activity and the formation of mineralized nodules in HDPCs. Moreover, suppression of p38α MAPK repressed the odontoblastic differentiation in HDPCs. Consistently, inhibition of p38α by SD-282 also decreased odontoblastic differentiation. p38α MAPK is involved in BMP-2-induced odontoblastic differentiation of HDPCs.
    International Endodontic Journal 03/2012; 45(3):224-33. · 2.05 Impact Factor
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    ABSTRACT: Bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor-β (TGF-β) superfamily, which has a broad range of activities that affect many different cell types. Previous research has suggested that BMP-2 induces the differentiation of human dental pulp cells (DPCs) into odontoblast-like cells. However, the mechanism by which BMP-2 induces odontoblastic differentiation has not yet been established. In the present study, we examined the involvement of the BMP/Smad pathway in mediating odontoblastic differentiation in DPCs. Levels of phosphorylated and unphosphorylated Smad1/5 were quantified by Western blot analysis in response to BMP-2 and the BMP signaling inhibitor noggin. Some nuclear translocation of Smad1/5 was also observed by immunofluorescence staining in isolated DPCs treated with BMP-2. The effects of noggin on the BMP-2-induced odontoblastic differentiation of DPCs were determined by alkaline phosphatase activity assay, and the expression of odontoblastic markers was evaluated by reverse transcription polymerase chain reaction analysis and Western blotting. We found that BMP-2 induced the phosphorylation and nuclear translocation of Smad 1/5. In addition, noggin significantly inhibited alkaline phosphatase activity and odontoblastic differentiation and reduced the formation of mineralized nodules in BMP-2-treated DPCs. These findings suggest that Smad 1/5 is involved in BMP-2-induced odontoblastic differentiation in DPCs.
    Journal of endodontics 01/2012; 38(1):66-71. · 2.95 Impact Factor
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    ABSTRACT: To investigate the nucleotide-binding oligomerization domain-2 (NOD-2) gene expression in deep caries and the effects of NOD-2 agonist muramyl dipeptide (MDP) on the differentiation of human dental pulp cells (hDPC). NOD-2 gene level in deep caries and healthy pulp tissue was determined by real-time quantitative polymerase chain reaction (realtime-PCR). Realtime-PCR, Western blotting and immunofluorescence were performed to evaluate NOD-2 gene and protein expression. Dentin sialoprotein (DSP) protein level was assessed when hDPC were challenged by different concentrations of MDP for 24 hours, and sialophosphoprotein (DSPP), osteocalcin (OCN) mRNA and osteopontin (OPN) protein level were detected at different time points after incubation with 0.1 mg/L MDP. NOD-2 mRNA level was higher in pulp tissue of deep caries (0.2610 ± 0.0824) than that in healthy controls (0.0024 ± 0.0002), P < 0.05. The expression of NOD-2 gene and protein increased in a time denpendent manner upon stimulation with MDP. Immunofluorescence confirmed that NOD-2 protein was located in cytoplasm. Moreover, 0.1 mg/L MDP augmented DSP protein level. DSPP and OCN mRNA were elevated with time and reached the peak at 12 h and down-regulated. OPN protein level also increased with time. Dental pulp NOD-2 expression are up-regulated in pulp tissue of deep caries. MDP may be related to the differentiation of hDPC.
    Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 07/2011; 46(7):412-6.
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    ABSTRACT: The serine/threonine kinase UNC-51-like kinase 1 (ULK1) plays an essential role in autophagosome formation, although the exact molecular mechanism is unknown. The present study was first to investigate the clinical and prognostic significance of ULK1 in esophageal squamous cell carcinoma (ESCC). Protein and mRNA levels of ULK1 in normal esophageal epithelial cells, ESCC cell lines, paired ESCC lesions and the adjacent noncancerous tissues were examined using western blot and real-time RT-PCR. The results showed that only the ULK1 protein level was upregulated in ESCC samples compared with normal esophageal cells and tissues. Also, we found that protein stabilization of ULK1 was higher in ESCC cell lines. Furthermore, immunohistochemical staining of ULK1 was performed on the tissue microarray containing 248 ESCC and 51 normal esophageal tissues. A total of 70.2% ESCC specimens showed intensive expression of ULK1 in contrast to the undetectable expression of ULK1 in normal esophageal tissues. Statistical analysis revealed that ULK1 expression was significantly correlated with T status (P = 0.048). Moreover, patients with higher ULK1 expression were associated with shorter overall survival time. Multivariate analysis suggested that ULK1 expression and N status (P < 0.001) were independent prognostic indicators for the survival of patients. Functional studies showed that suppression of ULK1 expression in ESCC cell lines by specific small interfering RNA resulted in inhibition of cell proliferation and induction of apoptosis under starvation conditions. These findings provide evidence that ULK1 represents a novel and clinically useful biomarker for ESCC patients and plays an important role during the progression of ESCC.
    Cancer Science 04/2011; 102(8):1568-75. · 3.48 Impact Factor
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    ABSTRACT: The nucleotide-binding oligomerization domain (NOD) proteins belong to a distinct family of proteins that are implicated in the intracellular recognition of bacterial components. NOD2 appears to be a sensor of bacterial peptidoglycans because it recognizes a minimal motif present in all peptidoglycans. The interaction of NOD2 with downstream signaling molecules ultimately results in the activation of NF-kappaB and production of inflammatory mediators in innate immunity. As such, NOD2 may play an important role in the detection of bacterial pathogens and the initiation of inflammation within the dental pulp. This study was designed to evaluate the expression of NOD2 in normal human dental pulp cells (HDPCs) and human pulp tissues. Human pulp tissue samples were collected from freshly extracted human wisdom teeth, and HDPCs were prepared from the explants of normal human dental pulp tissues. Nested reverse-transcription polymerase chain reaction (Nested RT-PCR) and Western blotting were performed to detect the expression of NOD2 messenger RNA and protein, respectively. Immunohistochemical staining was used to determine the distribution of NOD2 in the pulp tissues. The NOD2 messenger RNA and protein were present in normal human dental pulp tissues, with most NOD2 protein expression being localized to odontoblasts and some pulp vascular endothelial cells. In contrast, HDPCs only showed a low level of NOD2 protein expression. Our results suggest that NOD2 protein expressed in HDPCs and pulp tissues may play an important role in dental immune defense.
    Journal of endodontics 07/2009; 35(6):838-42. · 2.95 Impact Factor
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    ABSTRACT: Recombinant human bone morphogenetic protein-7 (BMP-7) has been shown to stimulate new reparative dentin formation in animal models. However, little is known about whether BMP-7 could promote the odontoblast-like differentiation and the formation of mineralized nodules in human dental pulp cells. Here, we reported that the infection with adenovirus-BMP-7 (Ad-BMP-7), a BMP-7-expressing adenoviral vector, induced the expression of BMP-7 in primarily cultured human dental pulp cells in the long term with little effect on their proliferation and viability. Importantly, BMP-7 expression significantly increased alkaline phosphatase activity and induced the dentin sialophosphoprotein expression in a dose- and time-dependent manner, suggesting that BMP-7 promoted the odontoblast differentiation. Furthermore, BMP-7 expression stimulated the formation of many mineralized dentin-like calcified nodules. Our data suggest that Ad-BMP-7-mediated BMP-7 expression can promote the differentiation of human pulp cells into odontoblast-like cells and mineralization in vitro, which may provide insight for the design of new gene therapy for the pulp capping in the clinic.
    Journal of Endodontics 09/2007; 33(8):930-5. · 2.93 Impact Factor
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    ABSTRACT: To investigate the effect of adenovirus expressing human bone morphogenetic protein-7 (hBMP-7) on proliferation and differentiation of human dental pulp cells. The replication-deficient adenoviral vector encoding hBMP-7 gene was constructed by using homologous recombinant modality. The efficiency of transfection was evaluated by fluorescent microscopy and flow cytometry. The expression of hBMP-7 protein in adenovirus-infected dental pulp cells was determined by Western blot. The proliferation of cells was tested by MTT method, the activity of alkaline phosphatase was assayed, von Kossa staining was used to detect mineralized nodule formation, and the expression of DSPPmRNA in cells was detected using semi-quantitative RT-PCR. Green fluorescent protein was visible under fluorescent microscopy. Higher transfection efficiency (91.1 +/- 1.0)% could be obtained at MOI of 75. Western blot from dental pulp cells infected with Ad-hBMP-7 for 48h detected protein expression of a hBMP-7 gene. The activity of alkaline phosphatase in cells was significantly higher than those of the control groups (P < 0.05). The cells infected with Ad-hBMP-7 had the ability of mineralization. DSPP mRNA expression of cells was in a time- and dose- dependent manner. Ad-hBMP-7 can induce human pulp cells into odontoblasts, but has no obvious effect on their proliferation.
    Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 11/2006; 41(10):612-5.
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    ABSTRACT: (100)-Orientation preferred BiFeO3–(Na0.5Bi0.5)TiO3 thin films with single perovskite phase and good crystallinity were successfully deposited on glass substrates by chemical solution deposition. X-ray diffraction analyses showed that the addition of (Na0.5Bi0.5)TiO3 to BiFeO3 can suppress the formation of secondary phases, promote the (100)-orientation growth, and improve the crystallinity of the films. Dense microstructure with evenly distributed grains about 100 nm was observed by scanning electron microscope. The optical measurements showed that the films have a conspicuous absorption in the blue and green light region and band gaps around 2.8 eV. These results demonstrated that BiFeO3–(Na0.5Bi0.5)TiO3 thin films deposited on glass substrates are promising candidates for optoelectronic or photovoltaic materials.
    Materials Letters. 71:60–62.
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    ABSTRACT: Highly (100)-oriented BiFeO3–(Na0.5Bi0.5)TiO3 thin films without undesirable phases were synthesized by chemical solution deposition. The preparation of BiFeO3–(Na0.5Bi0.5)TiO3 sol and deposition procedure were studied. BiFeO3–(Na0.5Bi0.5)TiO3 thin films were deposited onto SiO2/Si substrates via a sol–gel method, with LaNiO3 as buffer layer. X-ray diffraction analyses show that the BiFeO3–(Na0.5Bi0.5)TiO3 films are highly (100)-oriented due to lattice match growth. Smooth surface with evenly distributed grains as small as about 50nm were observed by scanning electron microscope. The dielectric and insulating characteristics against applied field, and optical properties were studied. It is found that the introduction of Ti4+ reduces the number of oxygen vacancy greatly and thus can suppress the leaking current. The film has a conspicuous absorption in the blue and green light region, and band gap of about 2.74eV.
    Journal of Alloys and Compounds · 2.73 Impact Factor