Combination of mineral trioxide aggregate and propolis promotes odontoblastic differentiation of human dental pulp stem cells through ERK signaling pathway.

The aim of this study is to investigate combined effects of mineral trioxide aggregate (MTA) and propolis on odontoblastic differentiation of human dental pulp stem cells (DPSCs) and to find a signaling pathway involved. Combination of MTA and propolis significantly up-regulated the expression of DSPP and DMP1, and facilitated a mineral nodule formation (p < 0.05). Treatments with MTA, propolis or combined increased the phosphorylation of extracellular signal-regulated kinases (ERK), one of mitogen-activated protein kinases signaling cascades during odontogenic differentiation of DPSCs (p < 0.05), and U0126, an inhibitor of ERK, decreased calcium deposits (p < 0.05). Combination of MTA and propolis promotes odontogenic differentiation and mineralization of DPSCs through ERK pathway.

Effect of Platelet-rich Fibrin on Odontoblastic Differentiation in Human Dental Pulp Cells Exposed to Lipopolysaccharide.

INTRODUCTION: Platelet-rich fibrin (PRF), as an autologous fibrin matrix, is known to contain platelets, leukocytes, and growth factors to control inflammation and to facilitate the healing process. The purpose of this study was to investigate the effects of PRF on odontoblastic differentiation in human dental pulp cells (HDPCs) treated with lipopolysaccharide (LPS). METHODS: Gene expression of inflammatory cytokines and adhesion molecules on the HDPCs cultured with or without LPS and PRF extract (PRFe) were evaluated by reverse-transcription polymerase chain reaction and Western blot analysis. In addition, odontoblastic differentiation was determined by measuring alkaline phosphatase (ALP) activity using ALP staining, the expression of odontogenesis-related genes, and the extent of mineralization using alizarin red S staining. RESULTS: Treatment with PRFe significantly attenuated the LPS-stimulated expression of interleukin (IL)-1ß, IL-6, and IL-8 in HDPCs. In addition, PRFe inhibited the up-regulation of vascular cell adhesion molecule 1 and the production of intracellular adhesion molecule 1 in HDPCs exposed to LPS. Expression of dentin sialophosphoprotein and dentin matrix acidic phosphoprotein 1, ALP activity, and mineralization were enhanced by PRFe in LPS-treated HDPCs. CONCLUSIONS: These results suggest that PRF has effects associated not only with inhibition of inflammation in HDPCs exposed to LPS but also stimulation of odontoblastic differentiation.

Combination of Mineral Trioxide Aggregate and Platelet-rich Fibrin Promotes the Odontoblastic Differentiation and Mineralization of Human Dental Pulp Cells via BMP/Smad Signaling Pathway.

INTRODUCTION: Recent reports have shown that the combined use of platelet-rich fibrin (PRF), an autologous fibrin matrix, and mineral trioxide aggregate (MTA) as root filling material is beneficial for the endodontic management of an open apex. However, the potential of the combination of MTA and PRF as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro has not yet been studied. The purpose of this study was to evaluate the effect of the combination of MTA and PRF on odontoblastic maturation in HDPCs. METHODS: HDPCs extracted from third molars were directly cultured with MTA and PRF extract (PRFe). Odontoblastic differentiation of HDPCs was evaluated by measuring the alkaline phosphatase (ALP) activity, and the expression of odontogenesis-related genes was detected using reverse-transcription polymerase chain reaction or Western blot. Mineralization formation was assessed by alizarin red staining. RESULTS: HDPCs treated with MTA and PRFe significantly up-regulated the expression of dentin sialoprotein and dentin matrix protein-1 and enhanced ALP activity and mineralization compared with those with MTA or PRFe treatment alone. In addition, the combination of MTA and PRFe induced the activation of bone morphogenic proteins (BMP)/Smad, whereas LDN193189, the bone morphogenic protein inhibitor, attenuated dentin sialophosphoprotein and dentin matrix protein-1 expression, ALP activity, and mineralization enhanced by MTA and PRFe treatment. CONCLUSIONS: This study shows that the combination of MTA and PRF has a synergistic effect on the stimulation of odontoblastic differentiation of HDPCs via the modulation of the BMP/Smad signaling pathway.

17ß-Estradiol induces odontoblastic differentiation via activation of the c-Src/MAPK pathway in human dental pulp cells.

The present study is aimed at investigating the effects of the exogenous estrogen 17ß-estradiol (E2) on odontoblastic differentiation in human dental pulp cells (HDPCs) immotalized with hTERT gene and their molecular mechanism. Proliferation was detected by BrdU assay, and odontoblast differentiation induction was evaluated by the expression of dentin sialophosphoprotein (DSPP), dentin sialoprotein (DSP) and dentin matrix protein1 (DMP1), and alkaline phosphatase (ALP) activity and mineralization. Estrogen receptor-α (ER-α), c-Src, and mitogen-activated protein kinases (MAPKs) were examined and their inhibitors were used to determine the roles on odontogenic induction. E2 significantly promoted the HDPC proliferation, which was mediated by extracellular signal-related kinase 1/2. E2 upregulated DSPP, DSP, and DMP1 as the odontogenic differentiation markers and enhanced ALP activity and mineralization. E2 increased phosphorylation of ER-α and fulvestrant, an ER downregulator, significantly downregulated DSPP, DMP1, and DSP induced by E2. Moreover, E2 treatment activated c-Src and MAPKs upon odontogenic induction, whereas chemical inhibition of c-Src and MAPKs decreased expression of DSPP, DMP1, and DSP and mineralization augmented by E2. Moreover, fulvestrant reduced E2-induced phosphorylation of c-Src and MAPK and inhibition of c-Src by PP2 attenuated activation of MAPKs during E2-induced odontoblastic differentiation. Taken together, these results indicated that E2 stimulates odontoblastic differentiation of HDPCs via coordinated regulation of ER-α, c-Src, and MAPK signaling pathways, which may play a key role in the regeneration of dentin.

Vitamin D Promotes Odontogenic Differentiation of Human Dental Pulp Cells via ERK Activation.

The active metabolite of vitamin D such as 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) is a well-known key regulatory factor in bone metabolism. However, little is known about the potential of vitamin D as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro. The purpose of this study was to evaluate the effect of vitamin D3 metabolite, 1α,25(OH)2D3, on odontoblastic differentiation in HDPCs. HDPCs extracted from maxillary supernumerary incisors and third molars were directly cultured with 1α,25(OH)2D3 in the absence of differentiation-inducing factors. Treatment of HDPCs with 1α,25(OH)2D3 at a concentration of 10 nM or 100 nM significantly upregulated the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein1 (DMP1), the odontogenesis-related genes. Also, 1α,25(OH)2D3 enhanced the alkaline phosphatase (ALP) activity and mineralization in HDPCs. In addition, 1α,25(OH)2D3 induced activation of extracellular signal-regulated kinases (ERKs), whereas the ERK inhibitor U0126 ameliorated the upregulation of DSPP and DMP1 and reduced the mineralization enhanced by 1α,25(OH)2D3. These results demonstrated that 1α,25(OH)2D3 promoted odontoblastic differentiation of HDPCs via modulating ERK activation.

Effect of nifedipine on the differentiation of human dental pulp cells cultured with mineral trioxide aggregate.

INTRODUCTION: Mineral trioxide aggregate (MTA) can induce differentiation of the dental pulp cells into odontoblast-like cells and generate a dentin-like mineral structure. The mechanisms underlying MTA-induced odontoblastic differentiation in human dental pulp cells (HDPCs) are not completely understood. The purpose of this study was to evaluate the effect of nifedipine as calcium channel blocker on MTA-induced odontoblastic differentiation in HDPCs. METHODS: HDPCs extracted from maxillary supernumerary incisors and third molars were directly cultured on MTA with or without nifedipine in the culture medium. Cell growth and expression of odontoblastic differentiation markers were determined by using methyl-thiazol-diphenyl-tetrazolium assay and reverse transcription-polymerase chain reaction analysis, respectively. Phosphorylation of mitogen-activated protein kinase was measured by Western blotting, and calcium deposition was assessed by using alizarin red S staining. RESULTS: MTA at a concentration of 1 mg/mL significantly up-regulated the expression of dentin sialophosphoprotein and dentin matrix protein-1 and enhanced mineralized nodule formation. However, nifedipine attenuated the MTA-induced odontoblastic differentiation in HDPCs. In addition, MTA-induced mineralization was blocked by inhibition of extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal kinase (JNK) by using U0126, SB203580, and SP600125, respectively. Furthermore, phosphorylation of ERK and JNK in response to MTA was inhibited when the medium was supplemented with nifedipine. CONCLUSIONS: This study showed that calcium ions released from MTA play an important role in odontoblastic differentiation of HDPCs via modulation of ERK and JNK activation.

A comparison of the BISAP score and serum procalcitonin for predicting the severity of acute pancreatitis.

BACKGROUND/AIMS: The bedside index of severity in acute pancreatitis (BISAP) is a new, convenient, prognostic multifactorial scoring system. As more data are needed before clinical application, we compared BISAP, the serum procalcitonin (PCT), and other multifactorial scoring systems simultaneously. METHODS: Fifty consecutive acute pancreatitis patients were enrolled prospectively. Blood samples were obtained at admission and after 48 hours and imaging studies were performed within 48 hours of admission. The BISAP score was compared with the serum PCT, Ranson's score, and the acute physiology and chronic health examination (APACHE)-II, Glasgow, and Balthazar computed tomography severity index (BCTSI) scores. Acute pancreatitis was graded using the Atlanta criteria. The predictive accuracy of the scoring systems was measured using the area under the receiver-operating curve (AUC). RESULTS: The accuracy of BISAP (≥ 2) at predicting severe acute pancreatitis was 84% and was superior to the serum PCT (≥ 3.29 ng/mL, 76%) which was similar to the APACHE-II score. The best cutoff value of BISAP was 2 (AUC, 0.873; 95% confidence interval, 0.770 to 0.976; p < 0.001). In logistic regression analysis, BISAP had greater statistical significance than serum PCT. CONCLUSIONS: BISAP is more accurate for predicting the severity of acute pancreatitis than the serum PCT, APACHE-II, Glasgow, and BCTSI scores.

A case of synchronous esophagus and stomach cancer successfully treated by combined chemotherapy.

Although cases of simultaneous esophagus and stomach cancer have been reported sporadically, there are rare reports of successful treatment using chemotherapy. We report a case of synchronous esophageal and gastric cancer successfully treated using docetaxel and cis-diammineedichloro-platinum (CDDP) combination chemotherapy instead of surgery. A 82-years-old man with anorexia and progressive weight loss was diagnosed with synchronous esophageal and gastric cancer by endoscopy. Both cancers were diagnosed as resectable by the preoperative clinical staging. However, surgery was contraindicated because of severe lung dysfunction. Moreover, he actively refused radiotherapy and endoscopic management. Therefore, the patient was given combined chemotherapy with docetaxel (65 mg/m²) and CDDP (60 mg/m²). The esophageal and gastric lesion completely disappeared on endoscopy, and there were no residual tumor cells on endoscopic biopsy after three cycles of chemotherapy. Metastatic lymph nodes also completely disappeared on the CT scan. The patient received a total of ten cycles of chemotherapy, without severe adverse effects. The patient remained asymptomatic for 18 months after discontinuation of the chemotherapy, without evidence of local recurrence or distant metastasis. Surgery or endoscopic treatment of both esophageal and gastric cancers is desirable, but, if medically inoperable, chemotherapy can be alternative treatment option.

Comparison of serum procalcitonin with Ranson, APACHE-II, Glasgow and Balthazar CT severity index scores in predicting severity of acute pancreatitis.

BACKGROUND/AIMS: The aim of this study is to assess serum procalcitonin (PCT) for early prediction of severe acute pancreatitis compared with multiple scoring systems and biomarkers. METHODS: Forty-four patients with acute pancreatitis confirmed by radiological evidences, laboratory assessments, and clinical manifestation were prospectively enrolled. All blood samples and image studies were obtained within 24 hours of admission. RESULTS: Acute pancreatitis was graded as severe in 19 patients and mild in 25 patients according to the Atlanta criteria. Levels of serum PCT were significantly higher in severe acute pancreatitis (p=0.001). The accuracy of serum PCT as a predicting marker was 77.3%, which was similar to the acute physiology and chronic health examination (APACHE)-II score, worse than the Ranson score (93.2%) and better than the Balthazar CT index (65.9%). The most effective cut-off level of serum PCT was estimated at 1.77 ng/mL (AUC=0.797, 95% CI=0.658-0.935). In comparision to other simple biomarkers, serum PCT had more accurate value (77.3%) than C-reactive protein (68.2%), urea (75.0%) and lactic dehydrogenase (72.7%). Logistic regression analysis revealed that serum PCT has statistical significance in acute severe pancreatitis. Assessment of serum PCT levels and length of hospital stay by simple linear regression analysis revealed effective p-value with low R square level, which could make only possibilty for affection of serum PCT to admission duration (r2=0.127, p=0.021). CONCLUSIONS: Serum PCT was a promising simple biomarker and had similar accuracy of APACHE-II scores as predicting severity of acute pancreatitis.