Nicotine inhibits osteogenic differentiation of human periodontal ligament cells under cyclic tensile stress through canonical Wnt pathway and α7 nicotinic acetylcholine receptor.

BACKGROUND AND OBJECTIVES: Nicotine, the main psychoactive component of tobacco, affects cell metabolism, proliferation, adhesion and, importantly, the osteogenic differentiation of fibroblasts. Approximately 15% of all orthodontic patients are adults among who one-fifth are smokers. Hence, it is necessary to have insight into the effects of nicotine on the osteogenic differentiation of hPDLCs during orthodontic tooth movement. This study aimed to investigate the effects and mechanisms of nicotine on the osteogenic differentiation of human periodontal ligament cells (hPDLCs) under the application of cyclic tensile stress. MATERIAL AND METHODS: hPDLCs were obtained from donor third molars. The hPDLCs were treated with nicotine and/or cyclic tensile stress that was applied with a cell stress plus unit. The effect of nicotine on cell viability was analyzed using the MTT assay. The osteogenic differentiation of hPDLCs was detected by alkaline phosphatase staining, Alizarin Red S staining, quantitative real-time polymerase chain reaction and western blotting. RESULTS: In combination with cyclic tensile stress, nicotine prevented the tensile stress-induced increase in alkaline phosphatase activity, formation of mineralization nodules and the upregulation of mRNA and protein expression of Runt-related transcription factor 2, transcription factor Sp7 and collagen type I; however, canonical Wnt pathway was activated. Furthermore, the addition of Dickkopf-related protein 1 and α-bungarotoxin counteracted the negative effect of nicotine and rescued the osteogenic differentiation of hPDLCs, respectively. CONCLUSION: These results indicate that nicotine prevents the increased osteogenic potential of hPDLCs induced by cyclic tensile stress by binding to an α7 nicotinic acetylcholine receptor and activating the canonical Wnt pathway.

Dehydration of sludge using the polyethylene glycol solution dialysis method and the mechanism of dehydration.

This study was undertaken to develops a new sludge dewatering technology based on polyethylene glycol solution dialysis. This method significantly reduced the final water content of sludge when compared to conventional dewatering methods. It was found that when the osmotic pressure difference between the polyethylene glycol solution and the sludge reached 8 MPa, the moisture content in the sludge was reduced to 28.6%, facilitating deep dehydration. To further improve the dehydration effect and explore the technical feasibility of dialysis dehydration, a dehydration experiment was designed using the polyethylene glycol solution dialysis method combined with external pressure. By applying external pressure to the dialysis membranes, the particles in the sludge were compacted, which reduced the internal voids of the sludge and propelled continuous water discharge. The results demonstrated that the dehydration effect was significantly improved when compared to single dialysis. A scanning electron microscope (SEM) was used to observe and quantitatively analyze the microstructure of the sludge before and after dehydration and to compare the variations in sludge microstructure throughout the dehydration process. The relationships between the sludge moisture content and the porosity and pore equivalent diameter were obtained. This demonstrated the effectiveness of the dewatering experiment using sludge dialysis combined with external pressure. This study also investigates the dehydration mechanism of this method during the sludge dehydration process. This study provides a novel solution for sludge volume reduction that can be applied to sewage treatment in the future.

Helical distraction is superior to linear and circular distraction in mandibular distraction osteogenesis: an in silico study.

Helical mandibular distraction is theoretically better than linear or circular distraction. However, it is not known whether this more complex treatment will result in unquestionably better outcomes. Therefore, the best attainable outcomes of mandibular distraction osteogenesis were evaluated in silico, given the constraints of linear, circular, and helical motion. This cross-sectional kinematic study included 30 patients with mandibular hypoplasia who had been treated with distraction, or to whom this treatment had been recommended. Demographic information and the computed tomography (CT) scans showing the baseline deformity were collected. The CT scans of each patient were segmented and three-dimensional models of the face created. Then, the ideal distraction outcomes were simulated. Next, the most favorable helical, circular, and linear distraction movements were calculated. Finally, errors were measured: misalignment of key mandibular landmarks, misalignment of the occlusion, and changes in intercondylar distance. Helical distraction produced trivial errors. In contrast, circular and linear distractions resulted in errors that were statistically and clinically significant. Helical distraction also preserved the planned intercondylar distance, while circular and linear distractions led to unwanted changes in the intercondylar distance. It is now evident that helical distraction offers a new strategy to improve the outcomes of mandibular distraction osteogenesis.

Efficacy of sequential use of telbivudine in hepatitis B e antigen-positive chronic hepatitis B patients with partial responses to pegylated interferon: a pilot study.

The aim of this study was to investigate the efficacy of sequential use of telbivudine in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients with partial responses to pegylated interferon. Patients with partial responses to 48 weeks of pegylated interferon treatment were divided into two groups. In group A, patients stopped pegylated interferon directly without sequential treatment. In group B, patients received sequential treatment with telbivudine 600 mg/day. HBeAg, HBeAb, hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT) and creatine kinase levels were determined at baseline and at weeks 12, 24, 36 and 48. Responses and safety were assessed after 48 weeks of telbivudine treatment. Thirty-six patients were recruited. Eighteen of these patients stopped pegylated interferon without sequential treatment (group A). After 48 weeks of follow-up, five patients (28%) had undergone HBeAg seroconversion, nine patients (50%) had undetectable levels of HBV DNA, and 11 patients (61%) achieved normal alanine aminotransferase (ALT) levels. The other 18 patients received sequential telbivudine treatment (group B). After 48 weeks of treatment, 11 patients (61%) had undergone HBeAg seroconversion, and all patients had undetectable levels of HBV DNA and normal ALT levels. All patients tolerated sequential telbivudine treatment, and only slightly elevated creatine kinase levels were observed. Switching to telbivudine therapy was efficient and safe in HBeAg-positive chronic hepatitis B patients with partial responses to 48 weeks of pegylated interferon. Sequential treatment with telbivudine resulted in an HBeAg seroconversion rate of 61% and an HBV DNA loss rate of 100% after 48 weeks. This promising strategy warrants further investigation.

Regulation of epidermal growth factor receptor signaling by plasmid-based microRNA-7 inhibits human malignant gliomas growth and metastasis in vivo.

MicroRNAs are endogenous, non-coding RNAs of approximately 20-22 nucleotides that regulate genes expression by binding to the 3' untranslated region (UTR) of targets mRNAs and play critical roles in cancer pathways. Malignant glioma is the most common and highly lethal central nervous system tumor for which little effective treatment is available over several decades. The purpose of this study was to explore the therapeutic potential of plasmid-based microRNA-7 (miR-7) for gliomas in vivo. Enhancing miR-7 levels in vitro could significantly induce cell apoptosis, and inhibit cell proliferation, cell migration and invasion. Western blotting analysis was performed, which indicated that miR-7 directly inhibited epidermal growth factor receptor (EGFR) and further antagonized the downstream protein kinases including ERK, Akt and Stat3. Furthermore, systemic administration of miR-7 encapsulated in cationic liposome resulted in glioma xenografts growth arrest and the metastatic nodules decrease effectively in a sequence-specific manner. In this study, miR-7 was applied in glioma treatment for the first time in vivo. Our findings suggested that the plasmid-mediated gene therapy with miR-7 appeared to be a promising candidate for the development of new antitumor and anti-metastasis treatment for human glioma.

Clinical feasibility of deep learning-based automatic head CBCT image segmentation and landmark detection in computer-aided surgical simulation for orthognathic surgery.

The purpose of this ambispective study was to investigate whether deep learning-based automatic segmentation and landmark detection, the SkullEngine, could be used for orthognathic surgical planning. Sixty-one sets of cone beam computed tomography (CBCT) images were automatically inferred for midface, mandible, upper and lower teeth, and 68 landmarks. The experimental group included automatic segmentation and landmarks, while the control group included manual ones that were previously used to plan orthognathic surgery. The qualitative analysis of segmentation showed that all of the automatic results could be used for computer-aided surgical simulation. Among these, 98.4% of midface, 70.5% of mandible, 98.4% of upper teeth, and 93.4% of lower teeth could be directly used without manual revision. The Dice similarity coefficient was 96% and the average symmetric surface distance was 0.1 mm for all four structures. With SkullEngine, it took 4 minutes to complete the automatic segmentation and an additional 10 minutes for a manual touchup. The results also showed the overall mean difference between the two groups was 2.3 mm for the midface and 2.4 mm for the mandible. In summary, the authors believe that automatic segmentation using SkullEngine is ready for daily practice. However, the accuracy of automatic landmark digitization needs to be improved.

Azithromycin in periodontal treatment: more than an antibiotic.

Azithromycin is a macrolide antibiotic used extensively in medicine for the treatment of a wide range of infections such as upper respiratory tract infections, middle ear infections, sexually transmitted infections and trachoma. It is also effective against the most common periodontopathogens. The versatility of the macrolides extends beyond their antibiotic properties as a result of their well-documented immune-modulating/anti-inflammatory effects. Macrolides, including azithromycin, are therefore used to treat diseases not associated with bacteria, such as severe asthma, chronic obstructive pulmonary diseases and, more recently, cystic fibrosis. Azithromycin is concentrated in neutrophils, macrophages and particularly fibroblasts; all of these cells are central players in the pathogenesis of most periodontal diseases. This paper reviews the diverse properties of azithromycin and the clinical periodontal studies of its effects in both the treatment of periodontitis and in resolving drug-related gingival overgrowth. Evidence exists to support the use of a single course of azithromycin in the treatment of advanced periodontal diseases. Azithromycin could have a triple role in the treatment and resolution of periodontal diseases: suppressing periodontopathogens, anti-inflammatory activity and healing through persistence at low levels in macrophages and fibroblasts in periodontal tissues, even after a single course of three tablets. If future periodontal research confirms these properties, it could become a valuable host-modulator in periodontal treatment.

Clinical feasibility evaluation of digital dental articulation for three-piece maxillary orthognathic surgery: a proof-of-concept study.

Digital dental articulation for three-piece maxillary orthognathic surgery is challenging. The purpose of this proof-of-concept study was to evaluate the clinical feasibility of a newly developed mathematical algorithm to digitally establish the final occlusion for three-piece maxillary surgery. Five patients with jaw deformities who had undergone a three-piece double-jaw surgery that was planned virtually were randomly selected for this study. The final occlusion had been hand-articulated using stone casts, scanned into the computer and used in the surgery. These hand-articulated occlusions served as the control group. To form the experimental group, the three-piece maxillary dental arch was articulated again automatically from the patient's original occlusion using the mathematical algorithm. The hand- and algorithm-articulated occlusions were then evaluated qualitatively by two experienced orthodontists. A quantitative evaluation was also performed. The results of the qualitative evaluation showed that all of the three-piece occlusions, hand- and algorithm-articulated, were clinically acceptable based on the American Board of Orthodontics grading system. When compared, two of the algorithm-articulated occlusions were clearly better (40%), one was the same (20%), and two were slightly worse (40%) than the hand-articulated occlusions. All of the quantitative measurements were comparable between the two articulation methods. In conclusion, the results of this study demonstrate that it is clinically feasible to digitally articulate the three-piece maxillary arch to the intact mandibular dental arch.

[Certain experiences in sequential treatment of occlusal reconstruction].

Occlusal reconstruction is a complex sequential treatment. The treatment may involve changes in occlusal vertical dimension and the full dental arch occlusal surface reconstruction. In this paper, we discussed the most concerned aspects of prosthodontists during the occlusal reconstruction sequential treatment, how to determine the suitable occlusal vertical dimension, rebuilding of occlusal plane, and consideratiom of temporomandibular joint disorders during reconstruction treatment. The prosthodontists should adopt the multidisciplinary collaboration mode of thinking in analysis, design, treatment, and restoration processes, regarding patients' individual characteristic through the occlusal reconstruction sequential treatment, and to reach healthy, functional, aesthetic outcome eventually.

The dental health status of 6 and 12 year-old Beijing schoolchildren in 1987.

There have been few epidemiological studies in China which have randomly selected subjects for examination. This study randomly selected 240 subjects aged 6 and 12 years from six schools in the Haidian District of Beijing, China. Examiners were calibrated and used standardised light sources and methods. Five per cent of the 6 year old children and 54 per cent of the 12 year old children were caries free. The dental caries treatment needs for 6 year old children were substantially greater in quantity and complexity than the needs of those aged 12 years. School based preventive and treatment programmes directed against the differing requirements of the age groups and supported by community-wide strategies for prevention appear as dental health matters of urgency in China.

Administration of PLGA nanoparticles carrying shRNA against focal adhesion kinase and CD44 results in enhanced antitumor effects against ovarian cancer.

The two membrane-bound proteins, focal adhesion kinase (FAK) and CD44, are involved in processes critical to cancer progression. FAK has an active role in angiogenesis, cell proliferation and cell apoptosis, whereas the heavily glycosylated CD44 has been implicated in cancer metastasis. Here, using short hairpin RNA (shRNA) against FAK and CD44, we demonstrate that simultaneous knockdown of both these genes inhibits cancer growth more efficiently than knockdown of either gene individually. Plasmids targeting these genes or non-relative control sequences were constructed and delivered to ovarian cancer targets by biodegradable poly D,L-lactide-co-glycolide acid nanoparticles (PLGANPs). Nude mice were utilized in an intraperitoneal model of ovarian carcinomatosis to assess antitumor efficacy in vivo. Single gene knockdown resulted in significantly smaller tumors than those observed in the empty-vector control (P's<0.001). More importantly, knockdown of both genes resulted in tumors smaller than both the empty-vector group (P<0.0001) and the single gene knockdown groups (P's<0.001). Knockdown of both FAK and CD44 resulted in tumors with inhibited angiogenesis, reduced proliferation and increased apoptosis as compared with controls (P's<0.001) and single knockdown groups (P's<0.05). These results indicate that dual knockdown of FAK and CD44 in the tumors of patients with ovarian cancer may have an enhanced therapeutic effect, and point toward a mechanism involving the inhibition of angiogenesis, cellular proliferation and the induction of apoptosis.

IL15 combined with Caspy2 provides enhanced therapeutic efficiency against murine malignant neoplasm growth and metastasis.

Interleukin-15 (IL15) is a potential immunotherapeutic treatment for cancer. Caspy2 is an active zebra caspase for inducing apoptosis and immune response in murine tumors. In this study, we aim to evaluate the potential of gene therapy using IL15 and Caspy2 against the murine tumors. Plasmid expressing both Caspy2 and IL15 genes was constructed, encapsulated in DOTAP/cholesterol cationic liposome and injected intratumorally into the mice bearing CT26, B16-F10 and 4T1 carcinoma. We found that coexpression of IL15 and Caspy2 could significant inhibit tumor growth and prolong survival of the mice bearing CT26 or B16F10 tumor. A significant reduction in spontaneous lung metastasis was observed in the 4T1 tumor model. In CT26 model, the mice treated with IL15 and Caspy2 acquired a long-time protective immunity against the parental tumor cell rechallenge. Cytotoxic T lymphocytes and terminal deoxynucleotidyltransferase-mediated nick end labelling assays showed that the combination of capsy2 and IL15 could enhance both the apoptosis and immune response induction, which may account for its extraordinary antitumor effect. Furthermore, we showed that the observed tumor suppression by IL15 and Caspy2 concurred with the Caspy2-mediated downregulation of IL10 and upregulation of interferon-γ and tumor necrosis factor-α. Our results therefore suggested that the combination regimen might be a novel and effective strategy for cancer treatment.

The treatment of oral cancer: an overview for dental professionals.

Oral cancer is a serious life-threatening disease. Dental professionals may be the first individuals to identify/suspect these lesions before referring to oral and maxillofacial surgeons and oral medicine specialists. Because the general dentist will likely follow on with the patient's future oral health, it is important that he or she has a basic understanding of the various treatments involved in treating oral malignancies and their respective outcomes. The four main modalities discussed in this review include surgery alone, radiotherapy alone, surgery with radiotherapy, and chemotherapy with or without surgery and radiotherapy. Chemotherapy has become an area of great interest with the introduction of new 'targeted therapies' demonstrating promising results in conjunction with surgery. Despite these results, the toxicities associated with chemotherapy regimens are frequent and can be severe, and therefore may not be suitable for all patients. Treatment modalities have improved significantly over the decades with overall decreases in recurrence rates, improved disease-free and overall survival, and an improved quality of life. Prognosis, however, is still ultimately dependent on the clinical stage of the tumour at the initial diagnosis with respect to size, depth, extent, and metastasis as recurrence rates and survival rates plummet with disease progression.

TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.

OBJECTIVE: To improve understanding of TRPV4-associated axonal Charcot-Marie-Tooth (CMT) neuropathy phenotypes and their debated pathologic mechanism. METHODS: A total of 17 CMT2C phenotypic families with vocal cord and diaphragmatic involvement and 36 clinically undifferentiated CMT2 subjects underwent sequencing analysis of the coding region of TRPV4. Functional studies of mutant proteins were performed using transiently transfected cells for TRPV4 subcellular localization, basal and stimulated Ca(2+) channel analysis, and cell viability assay with or without channel blockade. RESULTS: Two TRPV4 mutations R232C and R316H from 17 CMT2C families were identified in the ankyrin repeat domains. The R316H is a novel de novo mutation found in a patient with CMT2C phenotype. The family with R232C mutation had individuals with and without vocal cord and diaphragm involvement. Both mutant TRPV4 proteins had normal subcellular localization in HEK293 and HeLa cells. Cells transfected with R232C and R316H displayed increased intracellular Ca(2+) levels and reversible cell death by the TRPV channel antagonist, ruthenium red. CONCLUSION: TRPV4 ankyrin domain alterations including a novel de novo mutation cause axonal CMT2. Individuals with the same mutation may have nondistinct CMT2 or have phenotypic CMT2C with vocal cord paresis. Reversible hypercalcemic gain-of-function of mutant TRPV4 instead of loss-of-function appears to be pathologically important. The reversibility of cell death by channel blockade provides an attractive area of investigation in consideration of treatable axonal degeneration.

[Evaluation of dental diseases and clinical therapy of children in 1990, 1995].

OBJECTIVE: To study changes in patterns of children's dental diseases and their dental care improvements. METHODS: The survey was conducted on the basis of selection of 1,066 and 1,016 medical records of January, April, July and October of 1990 and 1995, respectively, from the complete hospital file. RESULTS: There was a distinct increase in pain and swelling as chief complaint, in regular check and in occlusal discrepancies, all with a significant difference of P < 0.01. No significant difference was found in caries and dental injury in both years. However in either of the two years caries remained the major dental disease. In dental treatment a significant difference (P < 0.01) indicated an increase in interception orthodontics and preventive treatment and a decrease in pulpal treatment. There was no remarkable differences in decay filling and extraction of teeth. CONCLUSION: The survey signified changes in patterns of children's dental diseases and evident improvement in children's dental therapy.

[The study on chemical composition and crystalline structure of hypoplastic primary dental enamel].

The present study, firstly, analyzed chemical composition of hypoplastic primary teeth by electron probe analyzer and compared the hypoplastic part with the normal part in the same tooth; secondly, by X-ray diffraction analyzer, studied the hypoplastic dental enamel and the normal dental enamel, and compared the crystalline structure between different dental enamel and with that of the hydroxyapatite. The aim was to find out any change of crystalline structure. Two exfoliated hypoplastic deciduous anterior teeth were used for the electron probe study. The normal part of each tooth served as control. Determinations of weight percentage (wt%) were made for P, Al, Mg, Ca, Mn, Fe, Zn, Sr, Na, K and F. Four exfoliated hypoplastic deciduous anterior teeth and eight exfoliated normal deciduous anterior teeth were used for the X-ray diffraction study. We found by X-ray diffraction that the length of the alpha-axis of enamel crystallite and the distance of lattice plane (corresponding 300) were increased in defective enamel and could be associated with the increased content of magnesium detected by electron probe. Thus, the present study demonstrated that there were both quantity and quality changes in the enamel hypoplasia lesion, which may increase the susceptibility of the defective teeth to caries.

[Clinical observation of dental pulp and root changes of juvenile anterior permanent teeth after concussion and luxation].

OBJECTIVE: To observe the incidence of pulp necrosis and root resorption of the juvenile anterior permanent teeth with concussion and luxation injuries and analyze the relationship between the type of injury and form of root resorption. METHODS: 157 teeth of 79 patients were chosen from 201 patients with concussion and luxation treated with functional-bite-plate at the Department of Pedodontics, School of Stomatology, Beijing Medical University from 1984 to 1996. RESULTS: High occurrence of pulp necrosis and root resorption were found in teeth with intrusion, and pulp necrosis occurred most within 3 months after the injury, while root resorption occurred during 3 weeks to 2 years. At the same time, surface resorption occurred mainly in the teeth with intrusion, extrusion and lateral luxation, and replacement resorption occurred only in intrusive teeth, however inflammatory resorption occurred in extrusive teeth whose pulp was infected. CONCLUSION: Intrusion is the most severe type of tooth trauma.