MiR-494-3p regulates skin fibroblast activities by mediating fibromodulin production.

Skin wound healing is a well-coordinated process in which various cells and factors participate, during which fibroblast exhibits a critical role by exerting its multiple activities, including proliferation, migration, invasion, and differentiation. Previous studies have identified that fibromodulin (FMOD) could enhance dermal wound healing by promoting skin fibroblast activities, but little is known about its upstream regulator. We occasionally found that FMOD expression was downregulated in skin fibroblast by transforming growth factor-ß1 treatment. It was hypothesized that microRNAs (miRNA) in skin fibroblast could downregulate FMOD production and blocking them would increase FMOD expression, as well as promote skin wound healing. Here, by utilizing combined analysis of miRNA microarray from the Gene Expression Omnibus database and miRNA targets prediction, we successfully identified a miRNA, termed miR-494-3p, could regulate FMOD production in human skin fibroblast (BJ fibroblast). The functional analysis revealed that miR-494-3p mimics could inhibit BJ fibroblast migration and invasion but not proliferation and differentiation, while miR-494-3p inhibition markedly promotes migration, invasion, and differentiation of BJ fibroblast. Moreover, we established FMOD overexpression (OE) and knockout BJ fibroblast. We found that FMOD OE could rescue the inhibitory effects of miR-494-3p mimics on the migration and invasion of BJ fibroblast. In contrast, the miR-494-3p inhibitor transfection could not enhance migration, invasion, and differentiation of FMOD KO BJ fibroblast. Together, our results suggest that miR-494-3p may be a potential target for skin wound management via regulating FMOD production.

Sublingual Gland Tumors Worldwide: A Descriptive Retrospective Study of 839 Cases.

PURPOSE: Sublingual gland tumors are rare. We sought to define the general features of sublingual gland tumors for clinical reference. In addition, we evaluated whether it would be safe to speculate that ∼90% sublingual gland tumors will be malignant and that ∼90% of those malignant tumors will be adenoid cystic carcinoma. MATERIALS AND METHODS: In the present study, we have reported data from a pleomorphic adenoma case of the sublingual gland and a case series of sublingual gland tumors. Global data of sublingual gland tumors were retrieved. The cases pathologically identified as either benign or malignant tumors of the sublingual gland were included. The demographic, pathologic, and treatment features were analyzed. RESULTS: Data from 1 recent case of pleomorphic adenoma of the sublingual gland and a 21-case series of sublingual gland tumors were retrieved. A total of 839 cases of sublingual gland tumors were analyzed in the present study. The most commonly encountered age group was 40 to 59 years (47.6%). Of the 367 patients with gender specified, 178 were men (48.5%) and 189 were women (51.5%). Malignant tumors predominated (n = 722 cases; 86.1% of 839). Most malignant tumors were adenoid cystic carcinoma (n = 376), just greater than one half (52.1%) of all malignant tumors. Surgery was the only reported treatment method for the benign tumors. The most common treatment methods for the 164 explicit malignant tumors were surgery plus radiotherapy for 82 patients (50%), followed by surgery alone for 70 patients (42.7%). CONCLUSIONS: To date and to the best of our knowledge, the present study is the most comprehensive study on the demographic, pathologic, and treatment features of global sublingual gland tumors. These findings have shown that ∼90% of sublingual gland tumors will be malignant. However, the assumption that ∼90% malignant sublingual gland tumors will be adenoid cystic carcinoma is incorrect, which could be a new critical clinical reference.

Bone morphogenetic protein-9 induces PDLSCs osteogenic differentiation through the ERK and p38 signal pathways.

Periodontal ligament stem cells (PDLSCs) with bone morphogenic ability are used to treat diseases such as periodontitis. Their treatment potential is increased when used in combination with proteins that induce osteogenic differentiation. For example, bone morphogenetic protein-9 (BMP9) has been found to have potent osteogenic activity. In the present study, PDLSCs were isolated from human periodontal membrane and infected with recombinant adenoviruses expressing BMP9 (Ad-BMP9). Levels of osteogenic markers such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) as well as mineralization ability were measured. The results showed that BMP9 promoted bone formation of PDLSCs. In other experiments, SB203580 and PD98059, which are inhibitors of p38 and ERK1/2, respectively, were used to determine if these kinases are involved in the osteogenic differentiation process. The resulting protein expression profiles and osteogenic markers of PDLSCs revealed that the mitogen-activated protein kinase (MAPK) signaling pathway might play an important role in the process of BMP9-induced osteogenic differentiation of PDLSCs.

Low-intensity pulsed ultrasound in the treatment of masticatory myositis and temporomandibular joint synovitis: A clinical trial.

BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) is a non-invasive physical stimulation application for the therapy of articular cartilage injury. This study aimed to explore the therapeutic effects of low-intensity pulsed ultrasound in treating masticatory myositis and synovitis in temporomandibular joint disorders and to establish an evaluation system to evaluate the clinical efficacy. METHODS: TMD patients who met the inclusion criteria in the temporomandibular joint clinic of the affiliated Stomatological Hospital of Chongqing Medical University from April 3, 2021, to December 2021 were selected. Before the start and after 7 days of LIPUS treatment, the Fricton temporomandibular joint disorder index, Visual Analog Scale (VAS), and Pressure Difference of Precision Manometer (PD) were measured. A paired t-test was used to compare the values of the Fricton index, VAS, and PD before and after treatment in each group. One-way ANOVA analysis of variance was used to compare the differences between groups. RESULTS: After one week of LIPUS treatment, the PI, DI and CMI of the Fricton index in the masticatory myositis (PI: P < 0.001; CMI: P < 0.001; DI: P = 0.2641, ns) and the synovitis group (DI: P < 0.001; CMI: P < 0.001, PI: P = 0.9729, ns) significantly decreased. The VAS of the masticatory myositis group and the synovitis group were significantly reduced (P < 0.001). The PD between the affected and healthy sides of the masticatory myositis group and the synovitis group was significantly reduced (P < 0.001), and the reduction was more evident in the M group. CONCLUSIONS: LIPUS is effective in pain relief in patients with masticatory myositis and joint synovitis, meanwhile, masticatory myositis was more sensitive to LIPUS. A new comprehensive clinical efficacy evaluation system which includes PV, FI, and VAS was created to better 2 diagnose masticatory myositis and joint synovitis.

The role of fibromodulin in inflammatory responses and diseases associated with inflammation.

Inflammation is an immune response that the host organism eliminates threats from foreign objects or endogenous signals. It plays a key role in the progression, prognosis as well as therapy of diseases. Chronic inflammatory diseases have been regarded as the main cause of death worldwide at present, which greatly affect a vast number of individuals, producing economic and social burdens. Thus, developing drugs targeting inflammation has become necessary and attractive in the world. Currently, accumulating evidence suggests that small leucine-rich proteoglycans (SLRPs) exhibit essential roles in various inflammatory responses by acting as an anti-inflammatory or pro-inflammatory role in different scenarios of diseases. Of particular interest was a well-studied member, termed fibromodulin (FMOD), which has been largely explored in the role of inflammatory responses in inflammatory-related diseases. In this review, particular focus is given to the role of FMOD in inflammatory response including the relationship of FMOD with the complement system and immune cells, as well as the role of FMOD in the diseases associated with inflammation, such as skin wounding healing, osteoarthritis (OA), tendinopathy, atherosclerosis, and heart failure (HF). By conducting this review, we intend to gain insight into the role of FMOD in inflammation, which may open the way for the development of new anti-inflammation drugs in the scenarios of different inflammatory-related diseases.

Catechol-Modified and MnO2-Nanozyme-Reinforced Hydrogel with Improved Antioxidant and Antibacterial Capacity for Periodontitis Treatment.

Periodontitis is an inflammatory disease characterized by tooth loss and alveolar bone resorption. Bacteria are the original cause of periodontitis, and excess reactive oxygen species (ROS) encourage and intensify inflammation. In this study, a mussel-inspired and MnO2 NPs-reinforced adhesive hydrogel capable of alleviating periodontitis with improved antibacterial and antioxidant abilities was developed. The hydrogel was created by combining polyvinyl alcohol (PVA), 3,4-dihydroxy-d-phenylalanine (DOPA), and MnO2 nanoparticles (NPs) (named PDMO hydrogel). The hydrogel was demonstrated to be able to scavenge various free radicals (including total ROS─O2•- and OH•) and relieve the hypoxia in an inflammatory microenvironment by scavenging excess ROS and generating O2 due to its superoxide dismutase (SOD)/catalase (CAT)-like activity. Besides, under 808 nm near-infrared (NIR) light, the photothermal performance of the PDMO hydrogel displayed favorable antibacterial and antibiofilm effects toward Escherichia coli, Staphylococcus aureus, and Porphyromonas gingivalis (up to nearly 100% antibacterial rate). Furthermore, the PDMO hydrogel exhibited favorable therapeutic efficacy in alleviating gingivitis in Sprague-Dawley rats, even comparable to or better than the commercial PERIO. In addition, in the periodontitis models, the PDMO2 group showed the height of the residual alveolar bone and the smallest shadow area of low density among other groups, indicating the positive role of the PDMO2 hydrogel in bone regeneration. Finally, the biosafety of the PDMO hydrogel was comprehensively investigated, and the hydrogel was demonstrated to have good biocompatibility. Therefore, the developed PDMO hydrogel provided an effective solution to resolve biofilm recolonization and oxidative stress in periodontitis and could be a superior candidate for local drug delivery system in the clinical management of periodontitis with great potential for future clinical translation.

Low-Intensity Pulsed Ultrasound Promotes Osteogenic Potential of iPSC-Derived MSCs but Fails to Simplify the iPSC-EB-MSC Differentiation Process.

Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) are a promising cell source for bone tissue engineering. However, iMSCs have less osteogenic potential than BMSCs, and the classical iPSC-EB-iMSC process to derive iMSCs from iPSCs is too laborious as it involves multiple in vitro steps. Low-intensity pulsed ultrasound (LIPUS) is a safe therapeutic modality used to promote osteogenic differentiation of stem cells. Whether LIPUS can facilitate osteogenic differentiation of iMSCs and simplify the iPSC-EB-iMSC process is unknown. We stimulated iMSCs with LIPUS at different output intensities (20, 40, and 60 mW/cm2) and duty cycles (20, 50, and 80%). Results of ALP activity assay, osteogenic gene expression, and mineralization quantification demonstrated that LIPUS was able to promote osteogenic differentiation of iMSCs, and it worked best at the intensity of 40 mW/cm2 and the duty cycle of 50% (LIPUS40/50). The Wnt/ß-catenin signaling pathway was involved in LIPUS40/50-mediated osteogenesis. When cranial bone defects were implanted with iMSCs, LIPUS40/50 stimulation resulted in a significant higher new bone filling rate (72.63 ± 17.04)% than the non-stimulated ones (34.85 ± 4.53)%. Daily exposure to LIPUS40/50 may accelerate embryoid body (EB)-MSC transition, but it failed to drive iPSCs or EB cells to an osteogenic lineage directly. This study is the first to demonstrate the pro-osteogenic effect of LIPUS on iMSCs. Although LIPUS40/50 failed to simplify the classical iPSC-EB-MSC differentiation process, our preliminary results suggest that LIPUS with a more suitable parameter set may achieve the goal. LIPUS is a promising method to establish an efficient model for iPSC application.

Hypoxia induces osteogenesis-related activities and expression of core binding factor α1 in mesenchymal stem cells.

Mesenchymal stem sells (MSCs) have received much attention in the field of bone tissue engineering due to their biological capability to differentiate into osteogenic lineage cells. Hypoxia-inducible factor 1alpha (HIF-1α) plays an important role in the MSC-related bone regeneration during hypoxia, while core binding factor alpha 1 (Cbfα1) is a transcription regulator that is involved in the chondrocyte differentiation and ossification. In the present study, we investigated the effects of hypoxia on biological capability of MSCs. MSCs were isolated from adult rabbit bone marrow, and were cultured in vitro under normoxia (air with 5% CO(2)) or hypoxia (5% CO(2) and 95% N(2)). The proliferation of MSCs, alkaline phosphatase (ALP) activity, and production of collagens type I and type III (Col I/III) were examined. The expression levels of HIF-1α and Cbfα1 were measured by real-time PCR and western blot analyses. We found that hypoxia significantly induced the proliferation of MSCs and increased ALP activity and the production of Col I/III. Moreover, hypoxia increased the expression of Cbfα1 mRNA after 12 h, whereas the expression of HIF-1α mRNA was increased after 1 h of hypoxia. Knockdown of HIF-1α expression with a small interfering RNA significantly increased the expression levels of Cbfα1 protein either under the normoxia or hypoxia condition. Our results indicate that hypoxia enhances MSCs to differentiate into osteogenic lineage cells and suggest that Cbfα1 may be negatively regulated by HIF-1α.

[Locally delivered macrolides as an adjunct to non-surgical periodontal treatment of chronic periodontitis: a meta analysis].

PURPOSE: The present meta analysis was designed to determine the effects of macrolides group of antibiotics as local drug delivery agents to scaling and root planing (SRP), compared with SRP alone or plus placebo. METHODS: Electronic and manual literature searches were conducted to select randomized controlled trials (RCTs) comparing SRP + macrolides versus SRP alone using the following databases: PubMed, Cochrane Library, Science Direct, EMbase, CNKI, Wanfang database and VIP data until August 2018. Two reviewers independently extracted the data and evaluated the methodological quality of the included studies. RevMan 5.3 was applied for meta analysis. RESULTS: Seven papers were obtained, which included 439 patients with chronic periodontitis.Meta analysis showed that in the two groups, the changes in probing depth（PD）[MD=0.77, 95%CI(0.48-1.05), P<0.00001], clinical attachment loss（CAL）[MD=0.74, 95%CI(0.39-1.10), P<0.0001],plaque index（PI）[MD=0.30, 95% CI(0.17-0.43), P<0.00001]，modified sulcus bleeding index (mSBI)[MD=0.23, 95%CI(0.15-0.32), P<0.00001]at 3 month and 6 month of PD[MD=1.15, 95%CI(0.41-1.89), P=0.002] were significantly different, the difference of CAL[MD=0.92, 95%CI(0.43-1.40), P=0.0002], PI[MD=0.51, 95%CI(0.07-0.95), P=0.02] and mSBI[MD=0.18, 95%CI(0.07-0.29), P=0.002] was also significant (P<0.05). CONCLUSIONS: SRP combined with local macrolides adjuvant treatment for chronic periodontitis is effective in short-term observation.

Association Between Toothbrushing and Behavioral Risk Factors of Non-communicable Diseases: A population Based Survey of 4500 adults in China.

Non-communicable Disease (NCD) related behavioral risk factors (BRF) plays a crucial role in NCD prevention, as does oral hygiene behavior in oral health promotion. We examined the association between NCD BRF and toothbrushing using data from a population-based survey, which recruited 4485 adults aged 18+ years, in Chongqing city, China. Prevalence of five NDC BRF and their clustering within individual were determined by toothbrushing frequency. Ordinal logistic regression examined the association between toothbrushing and BRF clustering. Prevalence of current smoking, insufficient intake of vegetable and fruit, and harmful use of alcohol increased significantly with toothbrushing frequency. Respondents who brushed teeth ≥2 times daily consumed more red meat than those with less frequent toothbrushing. Relative to those with no BRF, the adjusted cumulative odds ratio of brushing teeth less frequently was 2.1 (95% CI: 1.4-3.1) for respondents with 3+ BRF. The adjusted cumulative odds ratio was 1.5 (1.1-2.1) and 1.4 (1.0-1.8) for those who had two BRF and those who had one, respectively. Significant correlation between toothbrushing and NCD BRF implied that integrated intervention strategy involving the both may be beneficial in public health programs targeting at either oral health or NCDs, or both.

[p38 MAPK pathway mediated BMP9-induced osteogenetic differentiation of hPDLSCs].

PURPOSE: To determine the effect of p38 MAPK signaling pathway on BMP9-induced osteogenetic differentiation of human periodontal ligament stem cells( hPDLSCs)． METHODS： hPDLSCs were collected in vitro, and adenovirus vectors were used to infect hPDLSCs; then the activity and staining of alkaline phosphatase(ALP) were detected ,the expression of osteopontin (OPN) and osteocalcin(OCN) were detected by qPCR ，and the calcium nodule deposition was used to analyse the ability of BMP9-induced hPDLSCs osteogenetic differentiation. Phosphorylation of p38 and MKK3/6 was detected after hPDLSCs was intervened with Ad-BMP9 and SB203580 ( inhibitor of p38 MAPK signaling pathway) for 36 h respectively for the effect of the signaling pathway on osteogenic differentiation． SPSS16.0 software package was used for statistical analysis. RESULTS: Under the action of Ad-BMP9, the activity of ALP, the levels of osteopontin and osteocalcin genes were significantly higher than the control group (P<0.01). Staining of ALP and the calcium nodule deposition were consistent with the activity of ALP, the levels of osteopontin and osteocalcin. Western blot demonstrated that the expression of p-p38 and p-MKK3/6 was increased significantly. After adding SB203580, the expression of ALP, OPN and OCN was decreased significantly (P<0.01),and the calcium mineral deposits were also decreased. CONCLUSIONS: During hPDLSCs differentiation, BMP9 can induce osteogenesis, and MKK3/6-p38-MAPK pathway was involved in the osteogenesis and had positive regulation for osteogenesis of hPDLSCs.

[Platelet-rich plasma combined with demineralized freeze-dried bone allografts for periodontal regeneration in the treatment of periodontal defects: a meta-analysis].

PURPOSE: The aim of this meta analysis was to assess the influence of platelet-rich plasma (PRP)combined with demineralized freeze-dried bone allografts(DFDBA) on regeneration of periodontal periodontal defects by means of evaluating clinical and radiographic outcomes in prospective human clinical trials. METHODS: The following databases such as PubMed, The Cochrane Library, EMbase, CNKI, Wanfang data and VIP data were searched on computer from inception to December, 2016. According to the inclusion and exclusion criteria, two reviewers independently extracted the data，assessed the methodological quality of the included studies. RevMan 5.2 was applied for meta analysis. RESULTS: Six papers were obtained reviewed which included 205 periodontal bone defect sites. Six articles showed that there was no significant difference in probing depth decrease between PRP combined with DFDBA and PRP or DFBDA group[MD=0.35, 95%CI（-0.09，0.79), P=0.12], but there was significant difference in clinical attachment loss increase between the two groups［MD= 0.68，95%CI（0.41，0.94），P<0.00001]. Three articles were included for evaluating bone filling, there was significant difference in the distance from the cemento-enamel junction(CEJ) to the vertical bone defect(BD)(CEJ-BD)[MD=0.71，95%CI（0.46，0.95），P<0.00001]between the two groups; there was also significant difference in the distance from the alveolar crest to the vertical bone defect(AC-BD)[MD=0.64，95%CI（0.41，0.87)，P<0.00001]between the two groups. but there was no significant difference in the distance from the cemento-enamel junction(CEJ)to the alveolar crest (AC)(CEJ-AC)[MD=0.03，95%CI（-0.10，0.16），P=0.68] between the two groups. CONCLUSIONS: Within the limitations of this meta analysis, PRP combined with DFDBA is superior to PRP or DFDBA alone in clinical attachment loss and bone filling ,but there was no significant difference in probing depth. However, given the limited sample size and quantity of included studies, the above findings still need to be further proved by conducting more high-quality and large-scale RCTs.

Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps.

Surgical flaps are frequently affected by ischemia/reperfusion (I/R) injury. Calcium-sensing receptor (CaSR) and stromal cell-derived factor-1α (SDF-1α) are closely associated with myocardial I/R injury. This study was performed to evaluate the feasibility of applying SDF-1α to counteract CaSR activation-mediated I/R injury in ischemic free flaps. Free flaps that underwent ischemia for 3 h were equally randomized into five groups: CaCl2, NPS2143 + CaCl2, SDF-1α + CaCl2, AMD3100 + SDF-1α + CaCl2, and normal saline. The free flaps were harvested to evaluate flap necrosis and neovascularization after 2 h or 7 d of reperfusion. p-CaSR/CaSR was extensively expressed in vascular endothelial cells of free flaps after I/R injury, and activation of the SDF-1α/CXCR4 axis and NPS2143 could reduce the expression of cleaved caspase-3, caspase-9, FAS, Cyt-c, and Bax and increase Bcl-2 expression; the opposite was true after CaSR activation. Interestingly, initiation of the SDF-1α/CXCR4 axis might abrogate CaSR activation-induced I/R injury through enhancement of microvessel density. In conclusion, CaSR might become a novel therapeutic target of free flaps affected by I/R injury. Activation of the SDF-1α/CXCR4 axis and NPS2143 could counteract CaSR activation-mediated I/R injury and promote free flap survival through inhibition of caspase-3/caspase-9-related cell apoptosis and enhancement of neovascularization.

Impact on the upper airway space of different types of orthognathic surgery for the correction of skeletal class III malocclusion: A systematic review and meta-analysis.

OBJECTIVE: This study is aimed at assembling, through a systematic review and meta-analysis, scientific evidence related to the effects of mandibular setback (MdS) surgery and bimaxillary surgery for the correction of Class III malocclusion on the cross-sectional area (CSA) and volume of the upper airway as assessed using CT. METHODS: An electronic search was conducted on Cochrane Library, EMBASE, PubMed, Scopus and Web of Science up to June 20, 2016. The inclusion criteria were prospective or retrospective studies, with the aim of comparing the impact on the upper airway space of orthognathic surgery for the treatment of the skeletal class III malocclusion. The methodological index for non-randomized studies (MINORS) was chosen as the evaluation instrument and Revman5.3 was used for the meta-analysis. RESULTS: A total of 1213 studies were retrieved, of which only 18 met the eligibility criteria. The results of meta-analysis showed that the mean decrease in the upper airway volume after MdS surgery was 3.24 cm3 [95%CI (-5.25,-1.23), p = 0.85]; the mean decrease in minimum CSA after a combined surgery of maxillary advancement with mandibular setback (MdS + MxA) was 27.66 mm2 [95%CI (-52.81,-2.51), p = 0.51], but there was no significant decrease in upper airway volume (mean 0.86 cm3); comparison between MdS + MxA and isolated MdS showed significant differences in the CSA of the posterior nasal spine plane (PNS) and epiglottis plane (EP); statistically significant differences in nasopharynx volume (P < 0.0001) and upper airway total volume (P = 0.002) were observed, but no statistically meaningful variations existed in oropharynx volume (P = 0.08) and hypopharynx volume (P = 0.64). CONCLUSION: The results of this study suggest that bimaxillary surgery promotes less decrease on the upper airway than mandibular setback surgery alone for the correction of the skeletal class III malocclusion.

[Effect of low-intensity pulsed ultrasound combined with triamcinolone acetonide on oral mucosal ulcer healing in syrian hamster].

PURPOSE: To evaluate the effect of low-intensity pulsed ultrasound（LIPUS） combined with triamcinolone acetonide on oral mucosal ulcer in syrian hamster in several ways, including healing time, contents of superoxide dismutase（SOD）and malondialdehyde (MDA). METHODS: Sixty syrian hamsters were randomly divided into 5 groups, including a baseline group (containing a normal baseline group and a model baseline group, n=6) and 4 experimental groups (LIPUS processing and drug use group, LIPUS group, drug group and a normal control group without any processing, n=12). Four experimental groups and model baseline group were given oxygen free radicals to model the oral mucosal ulcer. At 24 h after the last treatment, the healing time of ulcer, content of SOD and MDA were compared between each group. SPSS 20.0 software package was used for statistical analysis. RESULTS: Compared with LIPUS group,drug group and control group, the healing time of oral mucosal ulcer in LIPUS and drug combined group was shortened. At 24 h after the last treatment, the activity of SOD showed that the LIPUS and drug combined group[(2.32±0.30) U/mgprot] were significantly higher than the model baseline group[(1.48±0.29) U/mgprot], the LIPUS group[(1.83±0.15) U/mgprot], the drug group[(1.76±0.25) U/mgprot] and control group[(1.71±0.18) U/mgprot] (P<0.05). The results of MDA content showed that the LIPUS and drug combined group [(8.17±0.21) nmol/mgprot] were significantly lower than the model baseline group[(9.41±0.22) nmol/mgprot], the LIPUS group[(9.00±0.44) nmol/mgprot], the drug group [(9.04±0.43) nmol/mgprot] and control group[(9.03±0.46) nmol/mgprot] (P<0.05). After oral mucosal ulcer healing, the activity of SOD and MDA showed that the LIPUS and drug combined group, the LIPUS group, the drug group and control group were not significantly different from the normal baseline group (P>0.05). CONCLUSIONS: Low-intensity pulsed ultrasound combined with triamcinolone acetonide can effectively improve the activity of SOD and reduce the contents of MDA in ulcerated tissues, and therefore accelerate the process of ulcer healing．.

[Clinical significance of calcitonin gene-related peptide level before and after treatment in patients with chronic periodontitis].

PURPOSE: To explore the clinical significance of calcitonin gene-related peptide (CGRP) levels in patients with chronic periodontitis before and after treatment, and to detect the calcitonin gene-related peptide content in human venous blood. METHODS: Thirty healthy controls and thirty patients with mild, moderate, severe periodontitis were enrolled from August 2014 to June 2015.CGRP level in the patients' peripheral blood was detected by ELISA. Three months after periodontal treatment, CGRP level in mild, moderate, severe periodontitis patients' peripheral blood was re-examined by ELISA. Then the correlation between calcitonin gene-related peptide and inflammation of chronic periodontitis was analyzed with SPSS 22.0 software package. RESULTS: The content of CGRP in healthy controls was significantly higher than that in patients with periodontitis. With the aggravation of periodontal inflammation, blood level of CGRP decreased gradually, and the lowest was in patients with severe periodontitis (P<0.01). Three months after periodontal treatment, CGRP content was significantly higher compared with that before treatment (P<0.05), but no significant difference was found in patients with different degree of periodontitis (P>0.05). CONCLUSIONS: The level of CGRP in venous blood decreased with the increasing severity of chronic periodontitis, and CGRP was negatively correlated with the degree of inflammation of chronic periodontitis. CGRP may be involved in the occurrence and development of chronic periodontitis. CGRP content in serum of patients with chronic periodontitis after treatment was significantly increased, CGRP may be used as the basis for clinical detection of chronic periodontitis.

Porphyromonas gingivalis lipopolysaccharide increases lipid accumulation by affecting CD36 and ATP-binding cassette transporter A1 in macrophages.

Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) promotes macrophage-derived foam cell formation, however, the mechanisms are not well established. In macrophages, lipid uptake is mediated by scavenger receptors including SR-A and CD36, while the cholesterol efflux is mediated by ATP-binding cassette transporter G1 (ABCG1), ABCA1 and SR-BI. We further investigated the mechanisms underlying the dysregulation by P. gingivalis LPS of these regulators resulting in the promotion of lipid accumulation in THP-1-derived macrophages. Our results showed that P. gingivalis LPS exacerbated lipid accumulation in oxidized low-density lipoprotein (oxLDL)-treated macrophages. However, cholesterol efflux was inhibited by P. gingivalis LPS in THP-1-derived macrophages. In oxLDL-untreated macrophages, P. gingivalis LPS treatment caused an increase in CD36 mRNA and protein levels, and a decrease in ABCA1 mRNA and protein levels, while having no effect on SR-A, SR-BI or ABCG1 expression. Upregulation of CD36 by P. gingivalis LPS resulted from activation of c-Jun/AP-1, and this was confirmed by the inhibition of increased CD36 expression after AP-1 inhibition using SP600125. However, the decreased protein stability of ABCA1 by P. gingivalis LPS was a result of increased calpain activity. Moreover, small hairpin RNA (shRNA) targeting heme oxygenase-1 (HO-1) augmented the P. gingivalis LPS-induced atherogenic effects on the expression of c-Jun/AP-1, CD36, ABCA1 and calpain activity. Accordingly, P. gingivalis LPS-regulated promotion of lipid accumulation in foam cells was also exacerbated by HO-1 shRNA. These results indicate that P. gingivalis LPS confers a exacerbation effect on the formation of foam cells by a novel HO-1-dependent mediation of cholesterol efflux and lipid accumulation in macrophages.

Tumor necrosis factor-α gene polymorphisms and risk of oral cancer: evidence from a meta-analysis.

Numerous studies have been conducted regarding association between TNF-α and oral cancer risk, but the results remain controversial. The present meta-analysis is performed to acquire a more precise estimation of relationships. Databases of Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI) were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated with fixed- or random-effect models. The heterogeneity assumption was assessed by I-squared test. Among the eight included case-control studies, all were focused on TNF-α-308G>A and four also concerned the TNF-α-238G>A polymorphism. It was found that oral cancer risk were significant decreased with the TNF-α-308G>A polymorphism in the additive genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00], P=0.05, I2=68.9%) and the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03, I2=52.4%); however, no significant association was observed in allele contrast (G vs. A, OR=0.70, 95% CI: [0.23, 2.16], P=0.54, I2=95.9%) and recessive genetic models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41, I2=93.1%). For the TNF-α-238G>A polymorphism, significant associations with oral cancer risk were found in the allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04], P=0.01, I2=0.0%) and recessive genetic models (GG vs. GA+AA, OR=2.23, 95%CI: [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates that TNF-α polymorphisms may contribute to the risk of oral cancer. Allele G and the GG+GA genotype of TNF-α- 308G>A may decrease the risk of oral cancer, while allele G and the GG genotype of TNF-α-238G>A may cause an increase.

Methylation status of the PTEN gene in adenoid cystic carcinoma cells.

The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is deficient in various types of human tumors due to mutations or epigenetic alterations. PTEN promoter hypermethylation is a major epigenetic silencing mechanism leading to self-repression in these tumors. The present study aimed to investigate whether PTEN promoter methylation is involved in the regulation of the PTEN gene in adenoid cystic carcinoma (ACC) cells. The expression of PTEN in ACC-2 cells was found to be significantly lower than that in normal salivary gland epithelial cells using RT-PCR analysis. The existence of CpG island methylation in the PETN promoter region in ACC-2 cells was demonstrated by methylation-specific PCR (MSP) analysis and direct sequencing of MSP product. RT-PCR, Western blot analysis and luciferase assay showed that mRNA and protein expression and the promoter activity of PTEN in ACC-2 cells treated with the DNA methylation inhibitor 5-aza-2-deoxycytidine were significantly up-regulated in a time-dependent manner. These results indicate that the hypermethylation of the PTEN promoter region leads to lower expression of PTEN gene in ACC cells, which aids in the development of PTEN as a molecular marker for the early diagnosis of this carcinoma.