Hongchen Liu

The transmembrane transport of metformin by osteoblasts from rat mandible

Previous studies have demonstrated that metformin, one of systemic antihyperglycemic drugs, can slow bone loss caused by diabetes mellitus and has an osteogenic action on osteoblasts in vitro. It is tempting to speculate that metformin would be transported into bone tissues around dental implant by topical administration to improve the bone-implant contact in diabetic patients. In this study, the osteoblasts from rat mandible were cultured with 5.5 mM (control) or 16.5 mM d-glucose, then the uptake of metformin by osteoblasts was detected with high performance liquid chromatography (HPLC). Rat organic cation transporter (rOct) expression was characterized by immunocytochemistry, RT-PCR and Western blotting. It was found that, the uptake of metformin was saturable, Na(+)-dependent, affected by extracellular pH and inhibited by both phenformin and cimetidine (an inhibitor of Octs). rOct1 but no rOct2 was expressed extensively in osteoblasts and the protein level of rOct1 could be up-regulated by metformin. The uptake of metformin and phosphorylated-rOct1 at hyperglycaemic cell culture (16.5 mM d-glucose) significantly increased versus 5.5 mM control (p < 0.05). In conclusion, rat osteoblasts have the ability to transport the metformin intra-cellularly, the uptake of metformin by osteoblasts is a secondary active transportation mediated by rOct1 and high-glucose can improve the uptake of metformin by osteoblasts through phosphorylation of rOct1. The current results suggest that metformin could be used for dental implant topically in type 2 diabetic patients to increase the bone formation, therefore, to enhance the success rate of dental implants clinically.

Porous Nanohydroxyapatite/Collagen Scaffolds Loading Insulin PLGA Particles for Restoration of Critical Size Bone Defect

Insulin is considered to be a classical central regulator of energy homeostasis. Recently, the effect of insulin on bone has gained a lot of attention, but little attention has been paid to the application in bone tissue engineering. In this study, porous nanohydroxyapatite/collagen (nHAC) scaffolds incorporating poly lactic-co-glycolic acid (PLGA) particles were successfully developed as an insulin delivery platform for bone regeneration. Bioactive insulin was successfully released from the PLGA particles within the scaffold, and the size of the particles as well as the release kinetics of the insulin could be efficiently controlled through Shirasu porous glass premix membrane emulsification technology. It was indicated that the nHAC/PLGA composite scaffolds possessed favorable mechanical and structural properties for cell adhesion and proliferation, as well as the differentiation into osteoblasts. It was also demonstrated that the nHAC/PLGA scaffolds implanted into a rabbit critical-size mandible defect possessed tissue compatibility and higher bone restoration capacity compared with the defects that were filled with or without nHAC scaffolds. Furthermore, the in vivo results showed that the nHAC/PLGA scaffolds which incorporated insulin-loaded microspheres with a size of 1.61 μm significantly accelerated bone healing compared with two other composite scaffolds. Our study indicated that the local insulin released at the optimal time could substantially and reproducibly improve bone repair.

Does a higher glycemic level lead to a higher rate of dental implant failure?: A meta-analysis.

BACKGROUNDnOwing to limited evidence, it is unclear whether diabetes that is not well controlled would lead to a higher rate of dental implant failure. The authors of this meta-analysis evaluated whether the failure rate for patients with diabetes that was not well controlled was higher than the failure rate for patients with well-controlled diabetes.nnnTYPES OF STUDIES REVIEWEDnThe authors searched PubMed, the Cochrane Library, and ClinicalTrials.gov without limitations for studies whose investigators compared the dental implant failure rates between patients with well-controlled diabetes and diabetes that was not well controlled. The authors pooled the relative risk (RR) and 95% confidence interval (CI) values to estimate the relative effect of the glycemic level on dental implant failures. The authors used a subgroup analysis to identify the association between the implant failure rate and the stage at which the failure occurred.nnnRESULTSnThe authors included 7 studies in this meta-analysis, including a total of 252 patients and 587 dental implants. The results of the pooled analysis did not indicate a direct association between the glycemic level in patients with diabetes and the dental implant failure rate (RR, 0.620; 95% CI, 0.225-1.705). The pooled RR in the subgroup of patients who experienced early implant failure was 0.817 (95% CI, 0.096-6.927), whereas in the subgroup of patients who experienced late implant failure, the pooled RR was 0.572 (95% CI, 0.206-1.586).nnnCONCLUSIONS AND PRACTICAL IMPLICATIONSnOn the basis of the evidence, the results of this meta-analysis failed to show a difference in the failure rates for dental implants between patients with well-controlled diabetes and patients with diabetes that was not well controlled. However, considering the limitations associated with this meta-analysis, the authors determined that future studies that are well designed and provide adequate controls for confounding factors are required.

Uptake of Metronidazole by Human Gingival Fibroblasts

BACKGROUNDnMetronidazole is an important antimicrobial agent for the therapeutic management of periodontal diseases and dentoalveolar infections. As in other tissues, the metronidazole concentration in gingival crevicular fluid is about equal to the plasma level. Thus, we hypothesized that metronidazole is not actively transported into human gingival fibroblasts.nnnMETHODSnUsing high performance liquid chromatography, the influences of extracellular metronidazole concentrations, temperature, pH, and inhibitors of transporters on the uptake of metronidazole by cultured human gingival fibroblasts were tested.nnnRESULTSnMetronidazole was taken up rapidly by fibroblasts; the intracellular metronidazole concentration reached the extracellular level in 3 minutes at 37 degrees C and in 2 minutes at 4 degrees C. The uptake of metronidazole by human gingival fibroblasts was not saturable, and the intracellular metronidazole concentrations increased linearly with the extracellular level. Temperature and pH had no significant influence on the uptake of metronidazole by fibroblasts. Probenecid and adenine had no influence on the uptake of metronidazole by fibroblasts. These findings indicate that metronidazole uptake does not involve a transporter. Metronidazole bound rapidly to human gingival fibroblasts, but the cell-associated drug declined progressively until it reached a stable plateau in 15 minutes.nnnCONCLUSIONSnMetronidazole rapidly entered human gingival fibroblasts via simple diffusion. Metronidazole easily reached the minimal inhibitory concentration in fibroblasts and gingiva. Given the fact that intracellular concentrations of metronidazole in other tissues and cells are also close to the plasma level, we speculate that metronidazole enters other tissues and cells via simple diffusion.

Post-operative Bleeding Risk in Dental Surgery for Patients on Oral Anticoagulant Therapy: A Meta-analysis of Observational Studies

Background and Objective: Minor dental surgery is invasive and hemorrhagic. Thus, in patients treated with anticoagulants, the bleeding risk related to these invasive procedures is concerning. The aim of this meta-analysis is to evaluate this risk by comparing the post-operative bleeding rates of oral anticoagulation treatment (OAT) patients (without interrupted or altered anticoagulant intake) with non-OAT patients. Methods: PubMed, Embase and the Cochrane Library were searched for eligible studies that compared the post-operative (following minor dental surgery) bleeding rates of OAT patients without interrupted or altered therapy with those of non-OAT patients. Relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were used to identify the association between the bleeding rate and different dental surgeries or anticoagulants. Results: Thirty two full text articles were assessed for eligibility and 20 studies were excluded according to the selection criteria. Finally, 12 studies and a total of 2102 OAT patients and 2271 non-OAT patients were included. A pooled analysis indicated that the post-operative bleeding risk in OAT patients is higher than that of non-OAT patients (RR: 2.794, 95% CI: 1.722–4.532, P = 0.000). The pooled RRs in the dental implant surgery and dental extraction subgroups were 2.136 (95% CI: 0.825–5.531, P = 0.118) and 2.003 (95% CI: 0.987–4.063, P = 0.054), respectively. As for the different oral anticoagulants, the pooled RR in the subgroup of new oral anticoagulants (NOACs) was 1.603 (95% CI: 0.430–5.980, P = 0.482), while the pooled RR in the vitamin K antagonists subgroup was 3.067 (95% CI: 1.838–5.118, P = 0.000). Conclusion: Under current evidence, OAT patients were under a higher post-operative bleeding risk than the non-OAT patients following minor dental surgery. For the dental implant surgeries and dental extractions, our study failed to demonstrate a higher risk of bleeding in the OAT patients compared with the non-OAT patients. Besides, The NOACs might be safer than the vitamin K antagonists in dental implant surgery. However, more well-designed studies are required for future research.

Surface Modification of Dental Titanium Implant by Layer-by-Layer Electrostatic Self-Assembly

In vivo implants that are composed of titanium and titanium alloys as raw materials are widely used in the fields of biology and medicine. In the field of dental medicine, titanium is considered to be an ideal dental implant material. Good osseointegration and soft tissue closure are the foundation for the success of dental implants. Therefore, the enhancement of the osseointegration and antibacterial abilities of titanium and its alloys has been the focus of much research. With its many advantages, layer-by-layer (LbL) assembly is a self-assembly technique that is used to develop multilayer films based on complementary interactions between differently charged polyelectrolytes. The LbL approach provides new methods and applications for the surface modification of dental titanium implant. In this review, the application of the LbL technique to surface modification of titanium including promoting osteogenesis and osseointegration, promoting the formation and healing of soft tissues, improving the antibacterial properties of titanium implant, achieving local drug delivery and sustained release is summarized.

Association between Myocardial Infarction and Periodontitis: A Meta-Analysis of Case-Control Studies

Background and Objective: Many clinical researches have been carried out to investigate the relationship between myocardial infarction (MI) and periodontitis. Despite most of them indicated that the periodontitis may be associated with an increased risk of MI, the findings and study types of these studies have been inconsistent. The goal of this meta-analysis was to critically assess the strength of the association between MI and periodontitis in case-control studies. Methods: PubMed and the Cochrane Library were searched for eligible case-control studies reporting relevant parameters that compared periodontal status between MI and control subjects. The odds ratios (ORs) and 95% confidence intervals (CIs) from each study were pooled to estimate the strength of the association between MI and periodontitis. The mean differences and 95% CIs for periodontal-related parameters were calculated to determine their overall effects. Results: Seventeen studies including a total of 3456 MI patients and 3875 non-MI control subjects were included. The pooled OR for the association between MI and periodontitis was 2.531 (95% CI: 1.927–3.324). The mean differences (95% CIs) for clinical attachment loss, probing depth, bleeding on probing, plaque index, and the number of missing teeth were 1.000 (0.726–1.247), 1.209 (0.538–1.880), 0.342 (0.129–0.555), 0.383 (0.205–0.560), and 4.122 (2.012–6.232), respectively. Conclusion: With the current evidence, the results support the presence of a significant association between MI and periodontitis. Moreover, MI patients had worse periodontal and oral hygiene status and fewer teeth than did control subjects. More high-quality and well-designed studies focusing on the casual relationship between MI and periodontitis should be conducted in the future.

Is there an association between IFN-γ +874A/T polymorphism and periodontitis susceptibility?: A meta-analysis.

Background: Interferon-&ggr; (IFN-&ggr;) is a key proinflammatory cytokine which plays a critical role in the pathogenesis and progression of periodontitis. The single nucleotide polymorphism of +874A/T in human IFN-&ggr; gene can influence the secretion of IFN-&ggr; and affect periodontitis susceptibility. However, the findings of published studies are inconsistent. Therefore, the goal of this meta-analysis is to investigate whether there is an association between IFN-&ggr; +874A/T polymorphism and periodontitis susceptibility. Methods: PubMed and the Cochrane Library were searched for eligible clinical studies. The odds ratio (OR) and 95% confidence interval (CI) of each study were pooled to estimate the strength of association between +874A/T and periodontitis. Subgroup analyses were performed to explore whether particular characteristics of studies were related to the overall results. Results: Seven studies and a total of 1252 periodontitis patients and 1622 periodontitis-free control subjects were included. No difference was observed in genotype distribution and allele frequency between periodontitis patients and control (T vs A: ORu200a = u200a1.01, 95% CI: 0.90–1.13, Pu200a = u200a.878; TT vs AA: ORu200a = u200a1.07, 95% CI: 0.87–1.32, Pu200a = u200a.537; AT vs AA: ORu200a = u200a1.00, 95% CI: 0.81–1.23, Pu200a = u200a.996; TT+AT vs AA: ORu200a = u200a1.00, 95% CI: 0.84–1.19, Pu200a = u200a.990; TT vs AA+AT: ORu200a = u200a1.03, 95% CI: 0.86–1.23, Pu200a = u200a.733). Besides, the subgroup analysis based on ethnicity, type of periodontitis, and smoking status failed to identify significant differences in each model, either. Conclusions: The results of this meta-analysis suggest that IFN-&ggr; +874u200aA/T polymorphism may not contribute to periodontitis susceptibility. High quality and well-designed studies which combine genetic and other environmental risk factors are needed to validate this conclusion in the future.

GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

Background: Delayed wound healing in diabetic patients is one of the most challenging complications in clinical medicine, as it poses a greater risk of gangrene, amputation and even death. Therefore, a novel method to promote diabetic wound healing is of considerable interest at present. Previous studies showed that injection of MSC-derived exosomes has beneficial effects on wound healing. In current studies, we aimed to isolate exosomes derived from gingival mesenchymal stem cells (GMSCs) and then loading them to the chitosan/silk hydrogel sponge to evaluate the effects of this novel non-invasive method on skin defects in diabetic rats. Methods: GMSCs were isolated from human gingival connective tissue and characterized by surface antigen analysis and in vitro multipotent differentiation. The cell supernatant was collected to isolate the exosomes. The exosomes were characterized by transmission electron microscopy, Western blot and size distribution analysis. The chitosan/silk-based hydrogel sponge was prepared using the freeze-drying method and then structural and physical properties were characterized. Then, the exosomes were added to the hydrogel and tested in a diabetic rat skin defect model. The effects were evaluated by wound area measurement, histological, immunohistochemical and immunofluorescence analysis. Results: We have successfully isolated GMSCs and exosomes with a mean diameter of 127 nm. The chitosan/silk hydrogel had the appropriate properties of swelling and moisture retention capacity. The in vivo studies showed that the incorporating of GMSC-derived exosomes to hydrogel could effectively promote healing of diabetic skin defects. The histological analysis revealed more neo-epithelium and collagen in the hydrogel-exosome group. In addition, the hydrogel-exosome group had the highest microvessel density and nerve density. Conclusions: The combination of GMSC-derived exosomes and hydrogel could effectively promote skin wound healing in diabetic rats by promoting the re-epithelialization, deposition and remodeling of collagen and by enhancing angiogenesis and neuronal ingrowth. These findings not only provide new information on the role of the GMSC-derived exosomes in wound healing but also provide a novel non-invasive application method of exosomes with practical value for skin repair.

Patients with Chronic Obstructive Pulmonary Disease Suffer from Worse Periodontal Health—Evidence from a Meta-Analysis

Background and Objective: It is widely accepted that there is an association between chronic obstructive pulmonary disease (COPD) and periodontitis. However, whether the periodontal status of the COPD patients is worse than that of the non-COPD subjects is seldom assessed. The findings currently available are inconsistent, some even contradictory. Therefore, we performed this meta-analysis to compare the periodontal health status of COPD patients and non-COPD subjects. Methods: PubMed and Embase were searched for all of the eligible studies which comparing the periodontal status between COPD patients and non-COPD subjects. The results of periodontal parameters in each study were extracted and the mean differences and 95% confidence intervals (CIs) for each parameter were calculated to determine their overall effects. Results: In total, 14 studies involving 3348 COPD patients and 20612 non-COPD controls were included and 9 periodontal indexes were analyzed. The mean differences (95% CIs) between COPD and non-COPD subjects for probing depth, clinical attachment loss, level of alveolar bone loss, plaque index, oral hygiene index, bleeding index, bleeding on probing, gingival index, and remaining teeth were 0.261 (0.020–0.501), 0.480 (0.280–0.681), 0.127 (0.000–0.254), 0.226 (0.043–0.408), 0.802 (0.326–1.279), 0.241 (−0.106 to 0.588), 6.878 (5.489–8.266), 0.364 (0.036–0.692), and −3.726 (−5.120 to −2.331), respectively. Conclusion: In summary, this meta-analysis demonstrates that the COPD patients suffer from worse periodontal health status, indicated by deeper periodontal pockets, high level of clinical attachment loss, worse oral hygiene, more inflammation and bleeding in the gingival tissue, and lower number of remaining teeth. Nevertheless, considering the limitations in our meta-analysis, more high-quality, and well-designed studies focusing on the periodontal health of the COPD patients are required to validate our conclusion.