Regulatory role of PDK1 via integrated gene analysis of mitochondria-immune response in periodontitis.

AIMS: To investigate the association between mitochondrial events and immune response in periodontitis and related regulatory genes. MAIN METHODS: Gene expression profiles in gingival tissues were retrieved from the Gene Expression Omnibus. Mitochondria-immune response-related differentially expressed genes (MIR-DEGs) between the healthy and periodontitis samples were determined. WGCNA, GO, and KEGG were used to investigate the function and the enriched pathways of MIR-DEGs. The correlation between MIR-DEGs expression and clinical probing pocket depth was analyzed. The MIR-DEGs were further identified and verified in animal samples. A periodontitis model was established in C57BL/6 mice with silk ligation. Micro-computed tomography was used to assess alveolar bone loss. Western blot, quantitative real-time polymerase chain reaction, and immunohistochemical analyses further validated the differential expression of the MIR-DEGs. KEY FINDINGS: A total of ten MIR-DEGs (CYP24A1, PRDX4, GLDC, PDK1, BCL2A1, CBR3, ARMCX3, BNIP3, IFI27, and UNG) were identified, the expression of which could effectively distinguish patients with periodontitis from the healthy controls. Enhanced immune response was detected in the periodontitis group with that in the healthy controls, especially in B cells. PDK1 was a critical MIR-DEG correlated with B cell immune response and clinical periodontal probing pocket depth. Both animal and clinical periodontal samples presented higher gene and protein expression of PDK1 than the control samples. Additionally, PDK1 colocalized with B cells in both animal and clinical periodontal tissues. SIGNIFICANCE: Mitochondria participate in the regulation of the immune response in periodontitis. PDK1 may be the key mitochondria-related gene regulating B-cell immune response in periodontitis.

Parental preferences for the procedural sedation of children in dentistry: a discrete choice experiment.

Purpose: The aim of this study was to explore parental preferences for the procedural sedation of children in dentistry through a discrete choice experiment (DCE) to inform clinical decisions and oral health management. Methods: Based on literature reviews, interviews with parents of pediatric dental patients, and expert consultation, six attributes, including fasting time, recovery time, sedative administration routes, adverse reactions, sedation depth and procedure cost, were incorporated into the DCE questionnaire. The DCE questionnaire collected data on parental preferences for pediatric dental sedation treatment from June to August 2022. A conditional logit model was used to analyze preference and willingness to pay (WTP) for each attribute and its level. Subgroup analyses assessing the impact of parents' dental anxiety on procedural sedation preferences were also conducted using conditional logit models. Results: A total of 186 valid questionnaires were gathered. Parents' preferences for fewer adverse reactions, a milder sedation depth, lower out-of-pocket cost, shorter fasting and recovery times and administration by inhalation were significantly associated with their choice of sedation model. The conditional logit model showed that parents were most interested in treatments with no adverse reactions (0% vs. 15%) (Coef, 1.033; 95% CI, 0.833-1.233), followed by those providing minimal sedation (vs. deep sedation) (Coef, 0.609; 95% CI, 0.448-0.769). Moreover, the relative importance of adverse reactions and fasting time was higher among anxious than nonanxious parents. The study found a WTP threshold of ¥1,538 for reducing adverse reactions (15% to 0%). The WTP threshold for the best sedation procedure scenario (no fasting requirement, 10 min recovery time, administration by inhalation, 0% adverse reaction incidence and minimal sedation) was ¥3,830. Conclusion: Reducing the adverse reactions and depth of sedation are predominant considerations for parents regarding procedural sedation in pediatric dentistry, followed by lower cost, shorter fasting and recovery times and inhalation sedation. Parents with dental anxiety had a stronger preference for options with a lower incidence of adverse reactions and shorter fasting time than parents without dental anxiety. This discovery is helpful for doctors and can promote collaborative decision-making among parents and doctors.

A randomized controlled trial: evaluation of efficiency and safety of a novel surgical guide in the extraction of deeply impacted supernumerary teeth in the anterior maxilla.

Background: Preoperative X-ray and cone-beam computed tomography (CBCT) are helpful for locating supernumerary teeth, but the images cannot be transferred to the operation. To design a novel surgical guide plate for intraoperative navigation, we transfer the patient's oral CBCT and gypsum model scan data to a computer for analysis. In our study, we evaluate the efficiency and safety of a novel surgical guide plate for the extraction of deeply impacted supernumerary teeth (DIMSNT) in the anterior maxilla. Methods: Forty patients treated at the Department of School & Hospital of Stomatology, Wenzhou Medical University from March 2019 to December 2020 with DIMSNT (type II/III according to Liu et al.) in the anterior maxilla were randomly divided into 2 groups (20 patients for each group) for the extraction. For group I, a novel surgical guide was selected using CBCT and gypsum model scan. In contrast, for group II who underwent freehand surgery, only the CBCT data was used. The evaluation of operation time, complications, satisfaction score, and the number of cases that underwent extraction immediately after removing the bone were performed to assess the efficiency and safety of this novel surgical plate. Results: All patients completed the surgery successfully. The guides for group I had a good application effect. Group I's operation time (23.35±5.39 min) was shorter than group II (29.60±9.76 min) (P=0.0194). The average pain degree of group I (1.8±1.08) was significantly less than group II (2.82±1.68) (P<0.05). The average swelling score of group I (34) was significantly less than group II (44.7). Patient satisfaction was significantly higher in group I (8.95±1.05) than in group II (7.90±1.51) (P=0.0152). Conclusions: The novel surgical guide assisted with DIMSNT extraction have been effective in improving the quality of the surgery, patient satisfaction, and reduce its difficulty and duration. We can construct a surgical guide plate to guide the incision and osteotomy in DIMSNT surgery through the data analysis of DIMSNT on computer, which has a broad application prospect for clinical use. Trial registration: Chinese Clinical Trial Registry ChiCTR2100054523.

P75 neurotrophin receptor positively regulates the odontogenic/osteogenic differentiation of ectomesenchymal stem cells via nuclear factor kappa-B signaling pathway.

p75NTR, a neural crest stem cell marker, is continuously expressed in mesenchymal cells during tooth development. Importantly, high expression of p75NTR in the late bell stage implicates its involvement in odontogenesis and mineralization. However, the regulatory mechanisms underlying p75NTR involvement in odonto/osteogenic differentiation remain unclear. Here, we investigate the effect and potential mechanisms underlying p75NTR involvement in odonto/osteogenic differentiation. We dissected EMSCs from the first branchial arches of mice embryo and compared the proliferation and migration of p75NTR+/+ and p75NTR-/-EMSCs by transwell, scratch and cell counting kit 8(CCK8)assays. The differentiation ability and the involvement of nuclear factor kappa-B (NF-κB) pathway were investigated through alkaline phosphatase and immunofluorescence assay, real-time PCR, and western blot. During induction of dental epithelium conditioned medium, p75NTR+/+ EMSCs exhibited deeper Alkaline phosphatase (ALP) staining and higher expression of odonto/osteogenic genes/proteins (e.g., dentin sialoprotein (DSPP) than p75NTR+/+ EMSCs. Moreover, p75NTR+/+ EMSCs exhibited higher nuclear P65 expression than p75NTR-/-EMSCs. Inhibition of NF-κB pathway with Bay11-7082 in p75NTR+/+EMSCs substantially decreased DSPP expression level. However, activation of NF-κB pathway with Bay11-7082 in p75NTR-/-EMSCs enhanced DSPP expression level. Thus, p75NTR possibly plays a paramount role in the proliferation and differentiation of EMSCs via NF-κB pathway.

Efficaciousness of dexmedetomidine in children undergoing cleft lip and palate repair: a systematic review and meta-analysis.

OBJECTIVE: To systematically assess the efficacy and safety of dexmedetomidine as an anaesthesia adjuvant for cleft lip and palate (CLP) repair in children. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP) and Wanfang (up to October 2020). Studies in languages other than English and Chinese were excluded. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) evaluating the impact of dexmedetomidine on emergence agitation (EA), the need for postoperative rescue analgesics, postoperative nausea and vomiting (PONV), and other adverse events in paediatric patients during CLP repair. DATA EXTRACTION AND SYNTHESIS: The quality of evidence was assessed by using the Cochrane Review Methods and the Grading of Recommendations Assessment, Development and Evaluation approach. Data were screened, extracted and assessed by two independent authors. Outcomes were reported as a risk ratio (RR) with a 95% CI. A random-effect model was used when heterogeneity was detected. RESULTS: Thirteen studies including 1040 children met the inclusion criteria. The incidence of EA was significantly decreased in the dexmedetomidine group (RR, 0.19; 95% CI 0.10 to 0.36; p<0.00001; I2=56%) as compared with the control group. Paediatric patients receiving dexmedetomidine had lower postoperative analgesic requirements (RR, 0.27; 95% CI 0.10 to 0.73; p=0.01; I2=84%) and a lower incidence of respiratory adverse events (RR, 0.49; 95% CI 0.31 to 0.78; p=0.003; I2=0%). There were no significant differences in the risk of PONV and cardiovascular adverse events. CONCLUSIONS: There was a lack of high-quality studies in this field. Perioperative administration of dexmedetomidine reduced the need for postoperative rescue analgesics and the incidence of EA in children without side effects undergoing CLP repair. However, further verification with larger samples and higher-quality RCTs is needed.

Involvement of MyoD and PEA3 in regulation of transcription activity of MDR1 gene.

Overexpression of multidrug resistance 1 (MDR1) in cancer remains one of the major causes for the failure of chemotherapy. In the present study, we found that MyoD and PEA3 could activate P-glycoprotein (P-gp) expression in SGC7901 cells. Knockdown of MyoD and PEA3 attenuated MDR1 expression and increased the sensitivity of multidrug resistant cancer cells to cytotoxic drugs that were transported by P-gp in SGC7901/VCR cells. MyoD or PEA3 could bind to the E-box and PEA3 sites on the MDR1 promoter and activate its transcription. The regulation of MDR1 expression by MyoD and PEA3 may provide potential ways to overcome MDR in cancer treatment.

Long non-coding RNA-ENST00000434223 suppresses tumor progression in gastric cancer cells through the Wnt/ß-catenin signaling pathway.

BACKGROUND: Gastric cancer (GC) develops from the lining of the stomach. The present study aimed to explore the effects of long non-coding RNA-ENST00000434223 (lncRNA ENST00000434223) on gastric cancer (GC) cells. METHODS: One hundred and four GC tissues and paracancerous tissues were collected from GC patients, and expression of ENST00000434223, Wnt2b, ß-catenin, cyclinD1, E-cadherin, N-cadherin, vimentin, and snail was subsequently assessed. Morphological changes in cells were assessed using an inverted microscope, and expression of Bcl-2, Bax and caspase-3 was examined. RESULTS: We found that expression of Wnt2b, ß-catenin, cyclinD1, N-cadherin, vimentin, and snail was increased in GC tissues, while expression of ENST00000434223 and E-cadherin was decreased. SGC-7901 cells were closely arranged, and expression of Wnt2b, ß-catenin, CyclinD1, N-cadherin, Vimentin, snail and Bcl-2 was increased, whereas expression of ENST00000434223, E-cadherin, Bax and caspase-3 was decreased. Furthermore, the rate of apoptosis was decreased and cell proliferation, invasion and migration were increased in response to downregulation of ENST00000434223. By contrast, upregulation of ENST00000434223 exhibited the opposite effects in MKN-45 cells. CONCLUSION: The results of this study provide a promising experimental basis for the treatment of gastric cancer through interventional targeting of lncRNA ENST00000434223.

microRNA­372 inhibits proliferation and induces apoptosis in human breast cancer cells by directly targeting E2F1.

Breast cancer is the most prevalent cancer and the leading cause of cancer­associated mortalities among women worldwide today. Accumulating evidence suggested that miR­372 may serve important roles in the initiation and development of various human cancers. However, the role of miR­372 in breast cancer remains unknown. The present study demonstrated that the expression level of miR­372 in human breast cancer tissues and cell lines is significantly reduced compared with normal breast tissues cell lines. Furthermore, results of functional assays indicated that miR­372 inhibits cell proliferation and induces apoptosis in the MCF­7 human breast cancer cell line. E2F1 was identified as a direct functional target of miR­372 in breast cancer. In conclusion, the findings revealed that miR­372 may have the potential to act as a novel molecule for the diagnosis and therapy of patients with breast cancer.

Synergistic interaction between MEK inhibitor and gefitinib in EGFR-TKI-resistant human lung cancer cells.

With the increasing use of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) in patients with advanced non-small cell lung cancer (NSCLC), acquired resistance has become a major clinical problem. A combination of different signaling pathway inhibitors is a promising strategy to overcome this. In the present study, the mitogen-activated protein kinase kinase 1/2 inhibitor, AZD6244, was used in combination with gefitinib to investigate the efficacy of this treatment in NSCLC cell lines, particularly in gefitinib-resistant cells. The EGFR-TKI-sensitive PC-9 (mutant EGFR/wild-type K-Ras) and EGFR-TKI-resistant A549 (wild-type EGFR/mutant K-Ras) human NSCLC cell lines were treated with AZD6244 alone, gefitinib alone or the combination of the two drugs, and the effects were evaluated using cell proliferation assays, with alterations in signaling pathways analyzed by western blotting. It was found that the growth inhibitory effect of combination treatment with gefitinib and AZD6244 was greater than that of gefitinib alone in the EGFR-TKI-resistant A549 cells. Treatment of A549 cells with gefitinib alone reduced the expression level of the activated form of Akt, and the combination of the two drugs showed stronger inhibition of phosphorylated-Akt and phosphorylated-extracellular signal-regulated kinases. The data showed that the combination of AZD6244 and gefitinib exhibited dose-dependent synergism in gefitinib-resistant NSCLC cells. Thus, a preclinical rationale exists for the use of AZD6244 to enhance the efficacy of gefitinib in patients with EGFR-TKI-resistant NSCLC.