GSTP1 rs4147581 C>G and NLRP3 rs3806265 T>C as Risk Factors for Chronic Obstructive Pulmonary Disease: A Case-Control Study.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory ailment influenced by a blend of genetic and environmental factors. Inflammatory response and an imbalance in oxidative-antioxidant mechanisms constitute the primary pathogenesis of COPD. Glutathione S-transferase P1(GSTP1) plays a pivotal role as an antioxidant enzyme in regulating oxidative-antioxidant responses in the pulmonary system. The activation of the NOD-like receptor thermal protein domain (NLRP3) inflammatory vesicle can trigger an inflammatory response. Several investigations have implicated GSTP1 and NLRP3 in the progression of COPD; nonetheless, there remains debate regarding this mechanism. Methods: Employing a case-control study design, 312 individuals diagnosed with COPD and 314 healthy controls were recruited from Gansu Province to evaluate the correlation between GSTP1 (rs4147581C>G and rs1695A>G) and NLRP3 (rs3806265T>C and rs10754558G>C) polymorphisms and the susceptibility to COPD. Results: The presence of the GSTP1 rs4147581G allele substantially elevated the susceptibility to COPD (CGvs.CC:OR=3.11,95% CI=1.961-4.935, P<0.001;GGvs.CC:OR=2.065,95% CI=1.273-3.350, P=0.003; CG+GGvs.CC:OR=2.594,95% CI=1.718-3.916, P<0.001). Similarly, the NLRP3rs3806265T allele significantly increased the susceptibility to COPD (TC:TT:OR=0.432,95% CI=0.296-0.630; TC+CCvs.TT:OR=2.132,95% CI=1.479-3.074, P<0.001). However, no statistically significant association was discerned between the rs1695A>G and rs10754558G>C polymorphisms and COPD susceptibility (P>0.05). Conclusion: In summary, this study ascertained that the GSTP1 rs4147581C>G polymorphism is associated with increased COPD susceptibility, with the G allele elevating the risk of COPD. Similarly, the NLRP3 rs3806265T>C polymorphism is linked to elevated COPD susceptibility, with the T allele heightening the risk of COPD.

Ultrafine particles exposure is associated with specific operative procedures in a multi-chair dental clinic.

Air quality in dental clinics is critical, especially in light of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, given that dental professionals and patients are at risk of regular exposure to aerosols and bioaerosols in dental clinics. High levels of ultrafine particles (UFP) may be produced by dental procedures. This study aimed to quantify ultrafine particles (UFP) concentrations in a real multi-chair dental clinic and compare the levels of UFP produced by different dental procedures. The efficiency of a high-volume evacuator (HVE) in reducing the UFP concentrations during dental procedures was also assessed. UFP concentrations were measured both inside and outside of a dental clinic in Shanghai, China during a 12-day period from July to September 2020. Dental activities were recorded during working hours. The mean (±standard deviation) concentrations of indoor and outdoor UFP during the sampling period were 8,209 (±4,407) counts/cm3 and 15,984 (±7,977) counts/cm3, respectively. The indoor UFP concentration was much higher during working hours (10,057 ± 5,725 counts/cm3) than during non-working hours (7,163 ± 2,972 counts/cm3). The UFP concentrations increased significantly during laser periodontal treatment, root canal filling, tooth drilling, and grinding, and were slightly elevated during ultrasonic scaling or tooth extraction by piezo-surgery. The highest UFP concentration (241,136 counts/cm3) was observed during laser periodontal treatment, followed by root canal filling (75,034 counts/cm3), which showed the second highest level. The use of an HVE resulted in lower number concentration of UFP when drilling and grinding teeth with high-speed handpieces, but did not significantly reduce UFP measured during laser periodontal therapy. we found that many dental procedures can generate high concentration of UFP in dental clinics, which may have a great health impact on the dental workers. The use of an HVE may help reduce the exposure to UFP during the use of high-speed handpieces.

Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway.

Osteoporosis bears an imbalance between bone formation and resorption, which is strongly related to oxidative stress. The function of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress is still unclear. Therefore, this study was aimed at identifying the protective effect of leonurine on H2O2 stimulated rat BMSCs. We found that leonurine can alleviate cell apoptosis and promote the differentiation ability of rat BMSCs induced by oxidative stress at an appropriate concentration at 10 µM. Meanwhile, the intracellular ROS level and the level of the COX2 and NOX4 mRNA decreased after leonurine treatment in vitro. The ATP level and mitochondrial membrane potential were upregulated after leonurine treatment. The protein level of PINK1 and Parkin showed the same trend. The mitophage in rat BMSCs blocked by 3-MA was partially rescued by leonurine. Bioinformatics analysis and leonurine-protein coupling provides a strong direct combination between leonurine and the PI3K protein at the position of Asp841, Glu880, Val882. In conclusion, leonurine protects the proliferation and differentiation of BMSCs from oxidative stress by activating mitophagy, which depends on the PI3K/Akt/mTOR pathway. The results showed that leonurine may have potential usage in osteoporosis and bone defect repair in osteoporosis patients.

Leonurine Promotes the Osteoblast Differentiation of Rat BMSCs by Activation of Autophagy via the PI3K/Akt/mTOR Pathway.

BACKGROUND: Leonurine, a major bioactive component from Herba leonuri, has been shown to exhibit anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effect of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) as a therapeutic approach for treating osteoporosis. MATERIALS AND METHODS: Rat bone marrow-derived mesenchymal stem cells (rBMSCs) were isolated from 4-weeks-old Sprague-Dawley rats. The cytocompatibility of leonurine on rBMSCs was tested via CCK-8 assays and flow cytometric analyses. The effects of leonurine on rBMSC osteogenic differentiation were analyzed via ALP staining, Alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. Additionally, autophagy-related markers were examined via qRT-PCR and Western blot analyses of rBMSCs during osteogenic differentiation with leonurine and with or without 3-methyladenine (3-MA) as an autophagic inhibitor. Finally, the PI3K/Akt/mTOR signaling pathway was evaluated during rBMSC osteogenesis. RESULTS: Leonurine at 2-100 µM promoted the proliferation of rBMSCs. ALP and Alizarin red staining results showed that 10 µM leonurine promoted rBMSC osteoblastic differentiation, which was consistent with the qRT-PCR and Western blot results. Compared with those of the control group, the mRNA and protein levels of Atg5, Atg7, and LC3 were upregulated in the rBMSCs upon leonurine treatment. Furthermore, leonurine rescued rBMSC autophagy after inhibition by 3-MA. Additionally, the PI3K/AKT/mTOR pathway was activated in rBMSCs upon leonurine treatment. CONCLUSION: Leonurine promotes the osteoblast differentiation of rBMSCs by activating autophagy, which depends on the PI3K/Akt/mTOR pathway. Our results suggest that leonurine may be a potential treatment for osteoporosis.

SPRC Suppresses Experimental Periodontitis by Modulating Th17/Treg Imbalance.

Object: The aims of the study were to explore the protective effects of S-propargyl-cysteine (SPRC) on periodontitis and to determine the underlying mechanisms. Methods: A rat periodontitis model was constructed by injecting LPS and SPRC (0, 25, and 50 mg/kg/d) was administered intraperitoneally. H2S and CSE level were detected. The alveolar bone level was evaluated by micro-CT, HE staining and methylene blue staining analysis. Inflammation-related factors, Treg and Th17 cells were detected by immunohistochemistry, RT-PCR, immunofluorescence, Western blot and flow cytometry. Phosphorylation levels of ERK1/2 and CREB were analysed. Results: The administration of SPRC significantly increased the expression of CSE in the gingival tissue and the concentration of endogenous H2S in the peripheral blood. Simultaneously, SPRC significantly inhibited the resorption of alveolar bone based on the H&E staining, micro-CT and methylene blue staining analysis. Compared with the periodontitis group, the levels of IL-17A, IL-10 were downregulated and IL-6,TGF-ß1 were upregulated in the SPRC groups. In the SPRC group, the percentage of TH17 cells and the expression of ROR-γt were downregulated, while the percentage of Tregs and the expression of Foxp3 were upregulated accompanied with inhibition of phosphorylation ERK1/2 and CREB. Conclusion: SPRC can prevent the progression of periodontitis by regulating the Th17/Treg balance by inhibition of the ERK/CREB signalling pathway.

LINC01315 Impairs microRNA-211-Dependent DLG3 Downregulation to Inhibit the Development of Oral Squamous Cell Carcinoma.

Recent studies have revealed that long non-coding RNAs (lncRNAs) involve in the progression of oral squamous cell carcinoma (OSCC). These lncRNAs have emerged as biomarkers or therapeutic targets for OSCC. We here aimed to investigate the role of lncRNA LINC01315 in OSCC and the related mechanisms. LINC01315 and DLG3 were determined to be poorly expressed while microRNA-211 (miR-211) was highly expressed in OSCC tissues and cells using RT-qPCR and western blot analysis. Based on the results obtained from dual-luciferase reporter gene, RIP, and FISH assays, LINC01315 was found to upregulate DLG3 expression by competitively binding to miR-211. Upon altering the expression of LINC01315, and/or miR-211 in OSCC cells with shRNA, mimic, or an inhibitor, we assessed their effects on OSCC cell proliferation, migration, invasion, and apoptosis. LINC01315 knockdown enhanced OSCC cell proliferation, migration and invasion, but dampened their apoptosis, all of which could be reversed by miR-211 inhibition. Elevation of DLG3, a target gene of miR-211, activated the Hippo signaling pathway, whereby suppressing OSCC progression in vitro. Finally, their roles in tumor growth were validated in vivo. These findings suggest that LINC01315 elevates DLG3 expression by competitively binding to miR-211, thereby suppressing OSCC progression.

Precision Medicine in Tissue Engineering on Bone.

With the rapidly development of clinical treatments, precision medicine has come to people eyes with the requirement according to different people and different disease situation. So precision medicine is called personalized medicine which is a new frontier of healthcare. Bone tissue engineering developed from traditional bone graft to precise medicine era. So scientists seek approaches to harness stem cells, scaffolds, growth factors, and extracellular matrix to promise enhanced and more reliable bone formation. This review provides an overview of novel developments on precision medicine in tissue engineering of bone hoping it can open new perspectives of strategies on bone treatment.

Chemical Stability and Antimicrobial Activity of Plasma-Sprayed Cerium Oxide-Incorporated Calcium Silicate Coating in Dental Implants.

PURPOSE: The aim of this study is to investigate the biological activity and antibacterial property of cerium oxide-incorporated calcium silicate coatings (CeO2-CS) in dental implants. MATERIALS AND METHODS: In this study, MC3T3-E1 cells cultured on the plastic, Ti-6Al-4V, and the cerium oxide-incorporated calcium silicate coatings (CeO2-CS) coating served as the blank, control, and CeO2-CS groups, respectively. A cell counting kit-8 (CCK-8) and flow cytometry were used to evaluate the biocompatibility. The osteoblastic differentiation of the MC3T3-E1 cells was also analyzed by quantitative real-time polymerase chain reaction analysis. The CCK-8 and counts of colony-forming units (CFUs) were used to detect the antibacterial activity of the coating on Enterococcus faecalis. The study showed that the cerium oxide-incorporated calcium silicate coating (CeO2-CS) has better biocompatibility. Meanwhile, the ALP, OCN, and BSP mRNA expression levels in the CeO2-CS group were significantly upregulated (P < 0.05). The number of viable bacteria and the CFU results were significantly reduced in the CeO2-CS group (P < 0.05). CONCLUSION: The cerium oxide-incorporated calcium silicate coatings (CeO2-CS) may promote the osteoblastic differentiation of osteoblasts. Meanwhile, the cerium oxide-incorporated calcium silicate coating (CeO2-CS) showed strong antimicrobial activity on E. faecalis, with good biocompatibility.

lncRNA PLAC2 activated by H3K27 acetylation promotes cell proliferation and invasion via the activation of Wnt/ß­catenin pathway in oral squamous cell carcinoma.

As a new group of important effector molecules involved in multiple cancer types, including breast cancer, lung cancer and oral squamous cell carcinoma, long noncoding RNAs (lncRNAs) have attracted considerable attention recently. However, the underlying cause that induces the dysregulated lncRNAs in cancer remains poorly understood. In the present study, the regulatory model of the lncRNA placenta­specific protein 2 (PLAC2) upregulation in oral squamous cell carcinoma (OSCC) was investigated and its biological functions in OSCC malignant progression was identified. A reverse transcription­quantitative polymerase chain reaction assay identified that PLAC2 is upregulated in OSCC cell lines and primary tissue samples. Furthermore, bioinformatic analysis followed by chromatin immunoprecipitation verified an enriched histone H3 on lysine 27 (H3K27) acetylation (H3K27ac) at the promoter region of the PLAC2 gene. Knockdown of cAMP­response element binding protein­binding protein (CBP) significantly reduced the enrichment level of H3K27ac, and thereby induced a decreased expression of PLAC2. Functionally, overexpression of PLAC2 promotes OSCC cell proliferation, migration and invasion, whereas knockdown of PLAC2 exerted an opposite effect. Furthermore, the Wnt/ß­catenin signaling pathway was activated by PLAC2 and mediated the PLAC2­induced malignant progress of OSCC. In conclusion, the present results indicated that lncRNA PLAC2 is transcriptionally activated by H3K27ac modification at the promoter region in OSCC, and promotes cell growth and metastasis via activating Wnt/ß­catenin signaling pathway. Therefore, PLAC2 may serve as a promising biomarker for OSCC prognosis and therapy.

miR-23a-3p suppresses cell proliferation in oral squamous cell carcinomas by targeting FGF2 and correlates with a better prognosis: miR-23a-3p inhibits OSCC growth by targeting FGF2.

Oral squamous cell carcinomas (OSCCs) are one of the most ubiquitous malignancies the world over, and are accompanied by a high mortality. microRNAs (miRNAs) have increasingly garnered attention with regards to the roles they play in initiation and progression of various kinds of cancers, including OSCC. It has been reported, that miR-23a-3p promotes the development of tumors for prostate cancer, gastric cancer and gliomas. The functions of miR-23a-3p in OSCC however, remain unclear. In this study, fibroblast growth factor 2 (FGF2) is revealed as a direct target of miR-23a-3p, based on luciferase assays and immunoblotting. The expression of miR-23a-3p and FGF2 were found to be significantly downregulated and upregulated in OSCC tissues respectively. This indicates a reverse correlation between miR-23a-3p and FGF2 levels. Using in vitro approaches we ascertained that miR-23a-3p might contribute to the inhibition of growth and inhibition through increasing apoptosis in OSCC cells; while an inhibitor of miR-23a-3p could reverse this effect. Examination of a clinical cohort of OSCC patients suggested that reduced expression of miR-23a-3p is correlated with more advanced cancerous stage and poorer differentiation of OSCC cell. Additionally, a survival analysis and the Cox-hazard regression model showed that higher levels of miR-23a-3p can be used reliably for prognosis of OSCC patients. This study indicates that miR-23a-3p might suppress tumor proliferation, invasion and promote apoptosis of OSCC by targeting FGF2. miR-23a-3p has the potential to be used as prognostic indicator, and could be exploited as a therapeutic reagent for OSCC in the future.

Protective effects of heme oxygenase-1-transduced bone marrow-derived mesenchymal stem cells on reduced­size liver transplantation: Role of autophagy regulated by the ERK/mTOR signaling pathway.

Autophagy is a critical lysosomal pathway that degrades cytoplasmic components to maintain cell homeostasis and provide substrates for energy metabolism. A study revealed that heme oxygenase-1 (HO-1)-transduced bone marrow-derived mesenchymal stem cells (BM-MSCs) could protect 50% reduced-size liver transplantation (RSLT) in a rat model. However, the mechanisms remain mostly unknown. The aim of the present study was to explore the effects and related mechanism of autophagy on the protection conferred by HO-1-transduced BM-MSCs (HO-1/BM-MSCs) on 50% RSLT in a rat model. The authors established an acute rejection model following 50% RSLT in rats, with recipients divided into three groups receiving treatment with BM-MSCs, HO-1/BM-MSCs or normal saline (NS) injected through the dorsal penile vein. Transplanted liver tissues at 0, 1, 3, 5, 7, 10 and 14 days following transplantation were acquired for further analysis. The results indicated that the expression of autophagy-related proteins LC3 and Beclin-1 increased, the levels of ERK and p-ERK increased, and the levels of mammalian target of rapamycin (mTOR) and p-mTOR decreased in the HO-1/BM-MSCs. These observations indicated that autophagy is involved in the protective effects of HO-1/BM-MSCs on liver grafts following RSLT, possibly via upregulation of autophagy-related proteins through the ERK/mTOR signaling pathway.

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation.

AIM: To investigate the effects of heme oxygenase-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation (RLT) in a rat model. METHODS: BMMSCs were isolated and cultured in vitro using an adherent method, and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs. A rat acute rejection model following 50% RLT was established using a two-cuff technique. Recipients were divided into three groups based on the treatment received: normal saline (NS), BMMSCs and HO-1/BMMSCs. Liver function was examined at six time points. The levels of endothelin-1 (ET-1), endothelial nitric-oxide synthase (eNOS), inducible nitric-oxide synthase (iNOS), nitric oxide (NO), and hyaluronic acid (HA) were detected using an enzyme-linked immunosorbent assay. The portal vein pressure (PVP) was detected by Power Lab ML880. The expressions of ET-1, iNOS, eNOS, and von Willebrand factor (vWF) protein in the transplanted liver were detected using immunohistochemistry and Western blotting. ATPase in the transplanted liver was detected by chemical colorimetry, and the ultrastructural changes were observed under a transmission electron microscope. RESULTS: HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver, and improve the liver function of rats following 50% RLT, with statistically significant differences compared with those of the NS group and BMMSCs group (P < 0.05). In term of the microcirculation of hepatic sinusoids: The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group (P < 0.01); HO-1/BMMSCs could inhibit the expressions of ET-1 and iNOS, increase the expressions of eNOS and inhibit amounts of NO production, and maintain the equilibrium of ET-1/NO (P < 0.05); and HO-1/BMMSCs increased the expression of vWF in hepatic sinusoidal endothelial cells (SECs), and promoted the degradation of HA, compared with those of the NS group and BMMSCs group (P < 0.05). In term of the energy metabolism of the transplanted liver, HO-1/BMMSCs repaired the damaged mitochondria, and improved the activity of mitochondrial aspartate aminotransferase (ASTm) and ATPase, compared with the other two groups (P <0.05). CONCLUSION: HO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly, and recover the energy metabolism of damaged hepatocytes in rats following RLT, thus protecting the transplanted liver.

The effect of delta-like 1 homologue on the proliferation and odontoblastic differentiation in human dental pulp stem cells.

INTRODUCTION: This study aimed to investigate the functions of delta-like homologue 1 (DLK1) in the proliferation and differentiation of human dental pulp stem cells (hDPSCs). METHODS: Immunohistochemical analysis was used to determine the expression of alkaline phosphatase (ALP), dentin sialophosphoprotein (DSPP), DLK1, NOTCH1 and p-ERK1/2 in the mouse first maxillary molar. Recombinant lentivirus was constructed to overexpress DLK1 stably in hDPSCs. The cell viability and proliferation of hDPSCs were examined by CCK8 and EdU incorporation assay respectively. The odontoblastic differentiation of hDPSCs was determined by detection of ALPase activity assay, ALP and alizarin red staining and the expression of mineralization-related genes including ALP, DSPP and dental matrix protein. The mRNA and protein levels of DLK1 and p-ERK1/2 protein expression were detected. ERK inhibitor was used to test the differentiation effect of DLK1 on hDPSCs. RESULTS: Delta-like homologue 1 was highly expressed on the odontoblasts and dental pulp cells on the first maxillary molar; the expression of p-ERK1/2 is similar with the DLK1 in the same process. The expression level of DLK1 increased significantly after the odontoblastic induction of hDPSCs. DLK1 overexpression increased the proliferation ability of hDPSCs and inhibited odontoblastic differentiation of hDPSCs. The protein level of p-ERK1/2 significantly increased in hDPSCs/dlk1-oe group. ERK signalling pathway inhibitor reversed the odontoblastic differentiation effects of DLK1 on hDPSCs. CONCLUSIONS: The proliferation of hDPSCs was promoted after DLK1 overexpression. DLK1 inhibited the odontoblastic differentiation of hDPSCs, which maybe through ERK signalling pathway.

DNA methylation is critical for tooth agenesis: implications for sporadic non-syndromic anodontia and hypodontia.

Hypodontia is caused by interactions among genetic, epigenetic, and environmental factors during tooth development, but the actual mechanism is unknown. DNA methylation now appears to play a significant role in abnormal developments, flawed phenotypes, and acquired diseases. Methylated DNA immunoprecipitation (MeDIP) has been developed as a new method of scanning large-scale DNA-methylation profiles within particular regions or in the entire genome. Here, we performed a genome-wide scan of paired DNA samples obtained from 4 patients lacking two mandibular incisors and 4 healthy controls with normal dentition. We scanned another female with non-syndromic anodontia and her younger brother with the same gene mutations of the PAX9,MSX1,AXIN2 and EDA, but without developmental abnormalities in the dentition. Results showed significant differences in the methylation level of the whole genome between the hypodontia and the normal groups. Nine genes were spotted, some of which have not been associated with dental development; these genes were related mainly to the development of cartilage, bone, teeth, and neural transduction, which implied a potential gene cascade network in hypodontia at the methylation level. This pilot study reveals the critical role of DNA methylation in hypodontia and might provide insights into developmental biology and the pathobiology of acquired diseases.

Expression and Function of PPARs in Cancer Stem Cells.

Cancer stem cells (CSCs) are cancer cells with characteristics of stem cells, especially the ability to arise to all types of cell in a particular cancer tissue. With the capacity to generate multiple types of cancer cells, CSCs are proposed as primary impetus for tumor initiation and metastases and are suggested as potential therapeutic targets for anti-cancer treatment. Peroxisome-proliferator-activated receptors (PPARs) are a subset of multifunctional transcription factors which play a pivotal role in cancer development and tumorigenesis. PPARs are also reported to be involved in the modulation of the epithelial-mesenchymal transition (EMT) process in CSC initiation and in the regulation of CSC functions. However, the exact mechanisms remain unknown. Herein, we review the latest evidence on the regulatory effects and mechanisms of PPARs in CSC formation and function, and evaluate the prospects of PPARs as a target for cancer treatment.

The Effect of NRAGE on cell cycle and apoptosis of human dental pulp cells and MDPC-23.

OBJECTIVES: Neurotrophin receptor-mediated melanoma antigen-encoding gene homology (NRAGE) is an important regulator of proliferation, cell cycle arrest and apoptosis. Our previous study showed that NRAGE is an important regulator of proliferation and odontogenic differentiation of mouse dental pulp cells. This study aimed to investigate the effects of NRAGE on the cell cycle and apoptosis on human dental pulp cells (hDPCs) and MDPC-23. MATERIALS AND METHODS: Cells were infected by recombinant lentivirus to stably knockdown the expression of NRAGE, then the biological effects of NRAGE on the MDPC-23 was detected. The cell cycle distributions and apoptosis of hDPCs and MCPC-23 were performed by flow cytometric analysis. Simultaneously, the cell cycle and apoptosis were also detected after cells treated with IKK inhibitor. RESULTS: The mRNA and protein levels of NRAGE decreased significantly after infected by recombinant lentivirus. Knockdown of NRAGE inhibited the apoptosis in hDPCs and MCPC-23. Knockdown of NRAGE show significantly G0G1 arrest in hDPCs, while no significantly difference in MDPC-23. Meanwhile, Knockdown of NRAGE activated the NF-κB signaling pathway. After treated with IKK inhibitor, the effect of NRAGE knockdown on apoptosis was reversed in both hDPCs and MDPC-23. CONCLUSION: NRAGE is a potent regulator for cell cycle and apoptosis of hDPCs. Knockdown of NRAGE inhibited apoptosis of hDPCs and MDPC-23 through the NF-κB signaling pathway.

Osteogenesis of bone marrow mesenchymal stem cells on strontium-substituted nano-hydroxyapatite coated roughened titanium surfaces.

OBJECTIVE: To investigate osteogenesis of bone marrow mesenchymal stem cells (BMSCs) on strontium-substituted nano-hydroxyapatite (Sr-HA) coated roughened titanium surfaces. METHODS: Sr-HA coating and HA coating were fabricated on roughened titanium surfaces by electrochemical deposition technique and characterized by field emission scanning electron microscope (FESM). BMSCs were cultured on Sr-HA coating, HA coating and roughened titanium surfaces respectively. Cell proliferation, alkaline phosphatase (ALP) activity, mineralized nodules formation and cell osteocalcin (OC) secretion were measured. RESULTS: Electrochemically deposited Sr-HA coating and HA coating had no effect on the proliferation of BMSCs and demonstrated that the materials have a good biocompatibility. BMSCs cultured on Sr-HA coating showed increased alkaline phosphatase activity, mineralized nodules formation, and cell OC secretion compared with the other two groups. Cells cultured on HA coating also showed increased biological activity compared with the roughened group. CONCLUSION: Sr-HA coated titanium surfaces by electrochemical deposition can promote osteogenesis of BMSCs in vitro and have the potential to shorten bone healing period and enhance implant osseointegration.

Biologic characteristics and osteogenic differentiation of maxillary primordium mesenchymal cells.

OBJECTIVE: The aim of this study was to investigate the biologic characteristics and osteogenic differentiation of mouse maxillary primordium mesenchymal cells (MPMCs) in vitro. METHODS: The MPMCs were obtained from the E13.5 mouse embryos and cultured in vitro. The biologic characteristics were studied based on general observation and 5-Bromo-2-deoxyUridine (BrdU) label. The MPMCs from the first passage were cultured in the osteogenic medium for 1 week. Then, the immunofluorescence staining, alkaline phosphatase staining, Alizarin red S staining, and quantity polymerase chain reaction were used to evaluate the osteogenic capability of MPMCs. RESULTS: The E13.5 MPMCs were successfully adherent cultured and passaged in vitro. These cells expressed Dlx2 and SMAD7, two genes that play important roles in the development of maxillary primordium. The percentage of 5-Bromo-2-deoxyUridine-labeled MPMCs was 32.1%. Osteogenic induction could promote the expression of Runx2, osteocalcin, and osteopontin, 3 osteogenic markers, in MPMCs. In addition, osteogenic induction could stimulate the secretion of alkaline phosphatase and promote the deposition of calcium nodules in MPMCs. CONCLUSIONS: The MPMCs could be cultured in vitro and could differentiate into osteoblast in vitro through osteogenic induction. It offered an alternative cell source to regenerate craniofacial bone and offered a useful cell model to study the craniofacial bone development.

The correlations between health-related quality of life changes and pain and anxiety in orthodontic patients in the initial stage of treatment.

This study aimed to assess generic health-related quality of life (HRQoL), pain intensity, and anxiety levels and the relationship between the three aspects in healthy young Chinese orthodontic patients in the early stage of orthodontic treatment. We enrolled 252 eligible participants (10-29 years old) to complete validated Chinese versions of questionnaires, including the State-Trait Anxiety Inventory (S-AI), the visual analogue scale (VAS), and the Short-Form 36-Item Health Survey (SF-36) at baseline and on days 1, 2, 3, 7, 14, and 30 after initial archwire placement (SF-36 only at baseline and day 30). The response rate was 96% (243 of 252). SF-36 had moderate reliability (Cronbach's alpha coefficient exceeding 0.7, good fit on day 30). Statistical significant changes were observed in physical function (P < 0.01), body pain (P = 0.01), and general health (P < 0.01) domains. Spearman correlation coefficients for SF-36 with S-AI were -0.131~-0.515 (P < 0.05); SF-36 with VAS were -0.141~-0.273 (P < 0.05), indicating significant but moderate negative correlations between HRQoL and pain/anxiety. Overall, the application of SF-36 in assessing HRQoL is reluctantly suitable for young Chinese orthodontic patients in the early stage of orthodontic treatment. Early treatment-related pain and anxiety are important factors in HRQoL.

Damage mechanisms in uniaxial compression of single enamel rods.

Enamel possesses a complex hierarchical structure, which bestows this tissue with unique mechanical properties. In this study, the mechanical behavior of single enamel rods was investigated under uniaxial compression. Numerical simulations were also performed using micromechanics models for individual enamel rods to identify the damage mechanisms contributing to the constitutive behavior. Experimental results showed that the single rods exhibited an elastic modulus ranging from 10~31 GPa, and that they undergo post-yield strain-hardening. The primary damage mode consisted of delamination within the assembly of mineral crystals. Results from numerical simulations suggest that strain localization within individual rods is responsible for the observed delamination, which is believed to arise from the non-uniform arrangement of mineral crystals. This mechanism was independent of mineral morphology and properties. The non-uniform crystal arrangement results in friction between crystals with different inclination angles and is believed to be responsible for the post-yield strain hardening behavior.