Enamel Matrix Derivative Enhances the Odontoblastic Differentiation of Dental Pulp Stem Cells via Activating MAPK Signaling Pathways.

The odontoblastic differentiation of dental pulp stem cells (DPSCs) contributes to pulp-dentin regeneration. Enamel matrix derivative (EMD) is considered to be a critical epithelial signal to induce cell differentiation during odontogenesis and has been widely applied to clinical periodontal tissue regeneration. The purpose of this study was to explore the effect of EMD on DPSCs proliferation and odontoblastic differentiation, as well as the underlying mechanisms. We conducted in vitro and in vivo researches to get a comprehensive understanding of EMD. In vitro phase: cell proliferation was assessed by a cell counting kit-8 (CCK-8) assay; then, alkaline phosphatase (ALP) activity and staining, alizarin red staining, real-time RT-PCR, and western blot analysis were conducted to determine the odontoblastic potential and involvement of MAPK signaling pathways. In vivo phase: after ensuring the biocompatibility of VitroGel 3D-RGD via scanning electron microscopy (SEM), the hydrogel mixture was subcutaneously injected into nude mice followed by histological and immunohistochemical analyses. The results revealed that EMD did not interfere with DPSCs proliferation but promoted the odontoblastic differentiation of DPSCs in vitro and in vivo. Furthermore, blocking the MAPK pathways suppressed the EMD-enhanced differentiation of DPSCs. Finally, VitroGel 3D-RGD could well support the proliferation, differentiation, and regeneration of DPSCs. Overall, this study demonstrates that EMD enhances the odontoblastic differentiation of DPSCs through triggering MAPK signaling pathways. The findings provide a new insight into the mechanism by which EMD affects DPSCs differentiation and proposes EMD as a promising candidate for future stem cell therapy in endodontics.

Profiling long noncoding RNA alterations during the stromal cell-derived factor-1α-induced odontogenic differentiation of human dental pulp stem cells.

OBJECTIVE: The purpose of this study was to investigate the differential expression of long noncoding RNAs (lncRNAs) in dental pulp stem cells (DPSCs) after stromal cell-derived factor-1α (SDF-1α) induction and to explore the lncRNAs that regulate the odontogenic differentiation and migration of DPSCs. DESIGN: We examined the altered expression of lncRNAs in DPSCs after SDF-1α induction by performing lncRNA microarray and qRT-PCR analyses. Moreover, a bioinformatics analysis was conducted to predict the interactions of lncRNAs and identify core regulatory factors. A small interfering RNA (siRNA) was used to knock down lncRNA AC080037.1 expression in DPSCs. Cell transmigration assays, alizarin red staining, qRT-PCR and Western blotting were performed to detect the expression of osteo/dentinogenic differentiation markers or Rho GTPase after lncRNA knockdown in DPSCs. RESULTS: The microarray analysis identified 206 differentially expressed lncRNAs at 7 days after treatment. One lncRNA, AC080037.1, was shown to regulate the odontogenic differentiation of DPSCs. An siRNA targeting lncRNA AC080037.1 suppressed DPSCs migration and the expression of Rho GTPase induced by SDF-1α. Moreover, AC080037.1 knockdown significantly affected mineralized nodule formation and substantially suppressed runt-related factor-2 (RUNX-2), dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) expression in DPSCs. CONCLUSIONS: Our results revealed the differential expression of lncRNAs in DPSCs before and after SDF-1α induction. Furthermore, we highlighted the significant involvement of one lncRNA, AC080037.1, in the positive regulation of the osteo/odontogenic differentiation of DPSCs and indicated that this lncRNA might be a potential target in regenerative endodontics. These findings may further advance translational studies of pulp engineering.

Central nervous system impairment detected by somatosensory evoked potentials in patients with Charcot-Marie-Tooth disease type 1A.

Diseases related to peripheral myelin protein 22 (PMP22) have been implicated to involve the central nervous system (CNS). This study aimed to detect central nerve impairment using somatosensory evoked potentials (SSEPs) in patients with Charcot-Marie-Tooth disease (CMT) 1A. A total of 30 CMT1A patients and 26 healthy volunteers were included. Baseline characteristics, brain MRI and segmental SSEPs were collected from the participants. The peak latencies of N9, N13 and N20 were recorded, and central conduction velocity (CCT) was calculated and compared between groups. Significant differences were found in the peak latencies and amplitudes of N9, N13 and N20 between the two groups. CCT was significantly prolonged in the CMT group (7.05 ± 2.09 ms) compared to the control group (5.40 ± 1.79 ms) (p = 0.003). Six of 30 CMT patients had abnormal MRI signals, but no correlation with CCT was found. The central somatosensory pathway that carries SSEPs was impaired in CMT1A patients, which implies an important underlying role of PMP22 in the CNS.

Association between skipping breakfast and risk of cardiovascular disease and all cause mortality: A meta-analysis.

BACKGROUND & AIMS: Previous studies on the association between skipping breakfast and risk of cardiovascular disease and all cause mortality have drawn controversial conclusions. Therefore, we carried out a meta-analysis to illuminate this association. METHODS: Studies about the association between skipping breakfast and risk of cardiovascular disease and all cause mortality were identified by searching Pubmed, Embase, Cochrane, and Web of Science databases until June 2019. Then we screened articles for eligibility, extracted data, and pooled the results using a random-effects model. RESULTS: Seven cohort studies concerning a total of 221,732 participants were included in this meta-analysis. Skipping breakfast was associated with elevated risk of cardiovascular disease (relative risk 1.22 95% confidence interval 1.10-1.35) and all cause mortality (relative risk 1.25 95% confidence interval 1.11-1.40) compared with eating breakfast regularly. CONCLUSION: Skipping breakfast increases the risk of cardiovascular disease and all cause mortality. Eating breakfast regularly may promote cardiovascular health and decrease all cause mortality.

Synergistic effects of stromal cell-derived factor-1α and bone morphogenetic protein-2 treatment on odontogenic differentiation of human stem cells from apical papilla cultured in the VitroGel 3D system.

Pulp-dentin regeneration in the apical region of immature permanent teeth represents a significant clinical challenge. Tissue engineering approaches using bioactive molecules and scaffolds may have the potential to regenerate the natural apical structure of these teeth, representing a superior alternative to existing treatment regimens. The aims of this study are (i) to evaluate the VitroGel 3D system, an animal origin-free polysaccharide hydrogel, as a possible injectable scaffold for pulp-dentin regeneration and (ii) to investigate the effects of stromal cell-derived factor-1α (SDF-1α) and bone morphogenetic protein-2(BMP-2) cotreatment on odontogenic differentiation of human stem cells from apical papilla (SCAP) cultured in the VitroGel 3D system. The morphology, viability and proliferation of SCAP cultured in the VitroGel 3D system were measured via scanning electron microscopy (SEM), live and dead cell staining and CCK-8 assays. Alkaline phosphatase (ALP) activity, real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) and Western blot analysis were further used to evaluate the odontogenic differentiation of SCAP cultured in the VitroGel 3D system in vitro. Finally, the odontogenic differentiation was assessed in vivo through ectopic subcutaneous injection. The results showed that SCAP cultured in 3D hydrogel demonstrated favorable viability and proliferation. SDF-1α and BMP-2 cotreatment enhanced odontogenic differentiation-related gene and protein expression in vitro and promoted odontogenic differentiation of SCAP in vivo. In conclusion, the present study demonstrated that the VitroGel 3D system promoted SCAP proliferation and differentiation. Moreover, SDF-1α cotreatment had synergistic effects on BMP-2-induced odontogenic differentiation of human SCAP cultured in the VitroGel 3D system both in vitro and in vivo.

Stromal-derived Factor-1α signaling is involved in bone morphogenetic protein-2-induced odontogenic differentiation of stem cells from apical papilla via the Smad and Erk signaling pathways.

Stromal-derived factor-1α (SDF-1α) is a chemokine signaling molecule that binds to the transmembrane receptor CXC chemokine receptor-4 (CXCR4) and carries out important functions in development tissue homeostasis. SDF-1α signaling via CXCR4 regulates the recruitment of stem and precursor cells to support tissue-specific repair or regeneration. In this study, we examined the contribution of SDF-1α signaling to the odontogenic differentiation of stem cells from the apical papilla (SCAP) induced by bone morphogenic protein 2 (BMP-2). CXCR4 expression was detected in cultured SCAP and SDF-1α promoted the migration of SCAP in Transwell assays. Blocking SDF-1α signaling by treatment with siRNA significantly affected BMP-2-induced mineralized nodule formation and alkaline phosphatase (ALP) activity. Moreover, blocking SDF-1α signaling inhibited the BMP-2-induced early expression of runt-related factor-2 (Runx-2) and strongly suppressed the induction of dentin matrix protein 1 (DMP-1) and dentin sialophosphoprotein (DSPP) expression by BMP-2. Furthermore, the interaction between SDF-1α and BMP-2 signaling was mediated via intracellular Smads and Erk activation. In conclusion, our results demonstrated that SDF-1α can significantly promote the migration of SCAP. Moreover, we revealed corequirement of the SDF-1α/CXCR4 signaling pathways in the BMP-2-induced odontogenic differentiation of SCAP, and these findings may be applied in new strategies for dental pulp regeneration.

Anger, hostility and risk of stroke: a meta-analysis of cohort studies.

OBJECTIVE: A growing number of studies have been conducted on the relationship between anger and hostility and the risk of stroke, and their conclusions are not consistent. Accordingly, we performed a meta-analysis to evaluate the relationship between anger and hostility and the risk of stroke. METHODS: We searched the PubMed and Embase databases for cohort studies, focusing on the relationship between anger and hostility and risk of stroke. Then studies were selected according to the inclusion and exclusion criteria. Study results were pooled using a random effects model. RESULTS: Ten studies from seven articles involving 52,277 participants were included in this meta-analysis. No significant association was found between anger and hostility level and risk of stroke (hazard ratio 1.08; 95% confidence interval 0.79-1.47). However, a positive association was seen when people with high socioeconomic status were excluded (hazard ratio 1.30; 95% confidence interval 1.06-1.59). CONCLUSION: A higher level of anger and hostility is not associated with elevated risk of stroke. However, the association is positive among people with lower socioeconomic status.

25-Hydroxyvitamin D Levels and the Risk of Dementia and Alzheimer's Disease: A Dose-Response Meta-Analysis.

Background and Purpose: Conclusions of previous cohort studies on the relationship between 25-hydroxyvitamin D level and the risk of dementia and Alzheimer's disease were not consistent. Thus, we performed a dose-response meta-analysis to evaluate this relationship by summarizing cohort studies. Methods: Pubmed, Embase, Cochrane, and Web of Science databases were searched for relevant studies. Cohort studies concerning the association between 25-hydroxyvitamin D level and dementia or Alzheimer's disease were included. Results of studies were pooled and the dose-response relationship was determined using a random-effect model. Results: Ten cohort studies, with 28,640 participants were included. A significant inverse relationship was found between 25-hydroxyvitamin D level and the risk of dementia and Alzheimer's disease. In addition, we found a linear dose-response relationship in that a 10 nmol/L increase in 25-hydroxyvitamin D level may lead to a 5% decrease in the risk of dementia (relative risk, 0.95; 95% confidence interval, 0.93-0.98) and 7% in the risk of Alzheimer's disease (relative risk, 0.93; 95% confidence interval, 0.89-0.97). Conclusion: Plasma or serum 25-hydroxyvitamin D concentration was inversely related to the risk of dementia and Alzheimer's disease, consistent with a linear dose-response relationship.