Alterations in oxidative stress biomarkers and helper T-cell subgroups in patients with periodontitis and IgA nephropathy.

OBJECTIVE: Investigating the changes in the oxidative stress levels and helper T lymphocyte (Th) subsets in patients with periodontitis and IgA nephropathy (IgAN) to determine their relationship. BACKGROUND: IgAN has a high prevalence, poor prognosis, and no effective cure. Accumulating evidence has implicated a close relationship between periodontitis and chronic kidney diseases, in which both IgAN and chronic periodontitis show chronic inflammation and abnormal metabolism. However, few studies have been conducted on the relationship between the two diseases from this perspective. METHODS: We divided 86 IgAN patients into patients with healthy periodontium (IgAN-H, n = 34) and patients with periodontitis IgAN (IgAN-P, n = 52); moreover, we divided 72 systemically healthy participants into patients with periodontitis (H-P, n = 35) and participants with healthy periodontium (H-H, n = 37). The proportions of Th subsets in peripheral blood were estimated using flow cytometry. Cytokine levels in plasma were assessed using cytokine assay kits. Enzyme-linked immunosorbent assay was used to evaluate the plasma levels of oxidative stress. RESULTS: Our results from analyzing the Th cell subsets indicated that Th2 cell counts in the IgAN-P group were significantly lower than those in the IgAN-H group, while Th17 cell counts were increased (p < 0.05). Moreover, the Th1/Th2 ratio and interleukin-6 levels in the IgAN-P group were significantly higher than those in the H-H group (p < 0.01). Compared with that in the H-H group, in the remaining three groups, plasma total oxidation state (TOS) levels were increased (p < 0.01), while plasma total antioxidant state (TAS) levels were decreased (p < 0.05). Furthermore, estimated glomerular filtration rate was negatively correlated with the probing depth and gingival bleeding index. IgAN was a risk factor for periodontitis, while TAS was a protective factor for periodontitis. The oxidative stress index (OSI) might be valuable for distinguishing periodontitis patients from healthy controls (area under the receiver operator characteristic curve = 0.951). CONCLUSION: IgAN is an independent risk factor of periodontitis, and the Th17 cell-mediated inflammatory response might be associated with the occurrence of periodontitis in patients with IgAN. Patients with coexisting IgAN and periodontitis exhibit increased oxidative stress, in which TOS and OSI are potential biomarkers for diagnosing periodontitis.

Effect of type 2 diabetes mellitus and periodontitis on the Th1/Th2 and Th17/Treg paradigm.

PURPOSE: To investigate the effect of type 2 diabetes mellitus (T2DM) and periodontitis on the Th1/Th2/Th17/Treg paradigm. METHODS: A total of 107 volunteers (aged 18-78 years) were recruited. Peripheral blood samples from patients with periodontitis and T2DM (n= 43), patients with periodontitis only (n= 20), patients with T2DM only (n= 23), and healthy controls (n= 21) were collected. Blood pressure, glycated hemoglobin, fasting plasma glucose, probing depth, gingival index, and clinical attachment loss were measured. The circulating proportions of Th1, Th2, Th17, and Treg cells were estimated by flow cytometry. The data were analyzed by a 2x2 factorial ANOVA. RESULTS: We observed higher ratios of Th1/Th2 and Th17/Treg cells among patients with T2DM (P< 0.05) than among healthy controls. The proportion of Th17 cells in patients with periodontitis and T2DM was higher than that in other groups (P< 0.05). T2DM exhibited a predominant effect on the proportion of Th1 cells (F= 18.127, P= 0.000) and the Th17/Treg ratio (F= 45.384, P= 0.000). A significant "T2DM x periodontitis" interaction effect on the proportion of Th2, Th17, Treg cells, and the Th1/Th2 ratio (P< 0.05) was also noticed. The area under curve of Th17 was 0.711 (95% CI= 0.584 to 0.803, P< 0.01) in the receiver operating characteristic curve analysis. CLINICAL SIGNIFICANCE: The results suggest that the proportion of Th2, Th17, Treg cells and the Th1/Th2 ratio is indicative of immune activation and inflammation, which are evident in patients with type 2 diabetes mellitus (T2DM) and periodontitis. The data indicate that the high expression of Th17 cells may be a relevant biological factor that can be associated with an increased risk of developing chronic periodontitis in patients with T2DM.

Operative treatments compared with nonoperative treatment of displaced midshaft clavicular fractures.

BACKGROUND: Few reports on external fixation to treat displaced midshaft clavicular fractures exist. We sought to compare the clinical effects of external fixation, plate fixation, and nonoperative treatment for treating displaced midshaft clavicular fractures in adults. MATERIAL AND METHODS: Eighty-nine patients with a displaced midshaft fracture of the clavicle were selected (according to inclusion criteria) for a retrospective analysis and assigned to either operative treatment with external fixation (29 patients), plate fixation (30 patients) or nonoperative treatment with a sling (30 patients). The average follow-up period is 32 months. Outcome analysis included: Constant shoulder score (CSS); disabilities of the arm, shoulder and hand score (DASH); nonunion rate; satisfaction of shoulder appearance. RESULTS: Eighty-five cases were successfully followed up. No significant difference was observed between external fixation and plate fixation (p > 0.05 and p = 0.132, respectively). The operative groups achieved better effects (p < 0.001) compared to the nonoperative treatment. The healing time of the three groups were: 10.4 ± 2.3 weeks for external fixation; 12.1 ± 2.5 weeks for plate fixation; and 15.7 ± 2.2 weeks for nonoperative treatment. In the follow-up, patients in the external fixation group (96%) and plate fixation group (93%) were more likely to be satisfied with the appearance of the shoulder than were those in the nonoperative group (77%). CONCLUSION: The external fixation and plate fixation are overall better than the nonoperative treatment. As to choose between the two, it depends on the local soft tissue condition, surgeon's techniques, communication between doctor and patients and so on.

Technological Research of a Clean Energy Router Based on Advanced Adiabatic Compressed Air Energy Storage System.

As a fundamental infrastructure of energy supply for future society, energy Internet (EI) can achieve clean energy generation, conversion, storage and consumption in a more economic and safer way. This paper demonstrates the technology principle of advanced adiabatic compressed air energy storage system (AA-CAES), as well as analysis of the technical characteristics of AA-CAES. Furthermore, we propose an overall architectural scheme of a clean energy router (CER) based on AA-CAES. The storage and mutual conversion mechanism of wind and solar power, heating, and other clean energy were designed to provide a key technological solution for the coordination and comprehensive utilization of various clean energies for the EI. Therefore, the design of the CER scheme and its efficiency were analyzed based on a thermodynamic simulation model of AA-CAES. Meanwhile, we explored the energy conversion mechanism of the CER and improved its overall efficiency. The CER based on AA-CAES proposed in this paper can provide a reference for efficient comprehensive energy utilization (CEU) (93.6%) in regions with abundant wind and solar energy sources.

Thermodynamic Analysis of a Hybrid Trigenerative Compressed Air Energy Storage System with Solar Thermal Energy.

The comprehensive utilization technology of combined cooling, heating and power (CCHP) systems is the leading edge of renewable and sustainable energy research. In this paper, we propose a novel CCHP system based on a hybrid trigenerative compressed air energy storage system (HT-CAES), which can meet various forms of energy demand. A comprehensive thermodynamic model of the HT-CAES has been carried out, and a thermodynamic performance analysis with energy and exergy methods has been done. Furthermore, a sensitivity analysis and assessment capacity for CHP is investigated by the critical parameters effected on the performance of the HT-CAES. The results indicate that round-trip efficiency, electricity storage efficiency, and exergy efficiency can reach 73%, 53.6%, and 50.6%, respectively. Therefore, the system proposed in this paper has high efficiency and flexibility to jointly supply multiple energy to meet demands, so it has broad prospects in regions with abundant solar energy resource.

Hepatic Loss of Borealin Impairs Postnatal Liver Development, Regeneration, and Hepatocarcinogenesis.

Borealin, a member of the chromosomal passenger complex, plays a key regulatory role at centromeres and the central spindle during mitosis. Loss of Borealin leads to defective cell proliferation and early embryonic lethality. The in vivo functions of Borealin in mammalian postnatal development, tissue homeostasis, and tumorigenesis remain elusive. We specifically analyzed the role of Borealin in regulating postnatal liver development, damage-induced liver regeneration, and liver carcinogenesis using mice carrying conditional Borealin alleles. Perinatal loss of Borealin caused increased genome ploidy and enlarged cell size in hepatocytes, likely due to the impaired function of the chromosomal passenger complex in mitosis. Borealin deletion also showed attenuated expansion of Sox9+HNF4α+ progenitor-like cells in liver regeneration during 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet-induced liver injury. Moreover, ΔN90-ß-Catenin and c-Met-induced hepatocarcinogenesis development was largely impeded by Borealin deletion. These findings indicate that Borealin plays a key role in liver development, regeneration, and tumorigenesis and suggests that Borealin could be a potential target for related liver diseases.

Hepatocellular carcinoma repression by TNFα-mediated synergistic lethal effect of mitosis defect-induced senescence and cell death sensitization.

UNLABELLED: Hepatocellular carcinoma (HCC) is a cancer lacking effective therapies. Several measures have been proposed to treat HCCs, such as senescence induction, mitotic inhibition, and cell death promotion. However, data from other cancers suggest that single use of these approaches may not be effective. Here, by genetic targeting of Survivin, an inhibitor of apoptosis protein (IAP) that plays dual roles in mitosis and cell survival, we identified a tumor necrosis factor alpha (TNFα)-mediated synergistic lethal effect between senescence and apoptosis sensitization in malignant HCCs. Survivin deficiency results in mitosis defect-associated senescence in HCC cells, which triggers local inflammation and increased TNFα. Survivin inactivation also sensitizes HCC cells to TNFα-triggered cell death, which leads to marked HCC regression. Based on these findings, we designed a combination treatment using mitosis inhibitor and proapoptosis compounds. This treatment recapitulates the therapeutic effect of Survivin deletion and effectively eliminates HCCs, thus representing a potential strategy for HCC therapy. CONCLUSION: Survivin ablation dramatically suppresses human and mouse HCCs by triggering senescence-associated TNFα and sensitizing HCC cells to TNFα-induced cell death. Combined use of mitotic inhibitor and second mitochondrial-derived activator of caspases mimetic can induce senescence-associated TNFα and enhance TNFα-induced cell death and synergistically eliminate HCC. (Hepatology 2016;64:1105-1120).

Th17 and Th1 Lymphocytes Are Correlated with Chronic Periodontitis.

T cells are involved in the homeostasis of periodontal tissues and mediate bone loss in periodontitis, but the involvement of T-helper cells in chronic periodontitis (CP) in a Chinese population is still unclear. This study aimed to assess the distribution of peripheral and local T helper (Th17) and Th1 in CP. Sixty-eight patients with CP and 43 healthy controls were recruited from April 2012 to July 2014 at the Department of Stomatology, People's Hospital of Xinjiang Uygur Autonomous Region (China). The proportions of Th17 (CD3(+)CD4(+)IL-17(+)) and Th1 (CD3(+)CD4(+)IFN-γ(+)) T-cells in peripheral blood samples were assessed by flow cytometry. Immunohistochemistry was used to quantify interleukin-17 (IL-17) and interferon-gamma (IFN-γ) protein levels in gingival biopsy samples. mRNA levels of IL-17, IFN-γ RORγt, and T-bet in gingival biopsy samples were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The proportions of circulating Th17 cells and Th1 cells were both more abundant in CP patients than in controls (Th17: 1.05% ± 0.87% vs. 0.62% ± 0.49%, P < 0.01; Th1: 13.93% ± 7.94% vs. 8.22% ± 4.50%, P < 0.001). Positive correlations were obtained between the proportion of circulating Th17 cells and probing depth (PD) (r = 0.320, P = 0.001) and between the proportion of circulating Th1 cells and PD (r = 0.372, P < 0.001). IL-17 and IFN-γ protein levels in gingival biopsy samples were markedly increased in CP compared to controls (both P < 0.05). Relative IFN-γ, IL-17A, and T-bet mRNA levels in CP biopsies were higher compared to controls (all P < 0.05). These results suggest that elevated peripheral and local Th17 and Th1 cells might be involved in the pathogenesis of CP.

Cytokine levels in plasma and gingival crevicular fluid in chronic periodontitis.

PURPOSE: To evaluate the Th1/Th2/Th17 cytokine levels in plasma and gingival crevicular fluid (GCF) from chronic periodontitis patients and healthy controls. METHODS: The concentration of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17, TNF, and IFN-γ were determined using a flow cytometric multiplex immunoassay (CBA), and was compared between the periodontitis group and the healthy group. Spearman rho coefficient was used to correlate cytokines in GCF in the periodontitis group and the healthy group, respectively. RESULTS: Comparisons of two groups of Th1/Th2/Th17 cytokine levels in plasma and GCF showed no statistically significant differences (P > 0.05), except Th17 (IL-17) level in plasma that was higher in the periodontitis group than the healthy group (P < 0.05). A stronger correlation between IL-17/IL-4 and IL-17/IL-10 was observed in periodontitis patients than in healthy controls.

Hepatic loss of survivin impairs postnatal liver development and promotes expansion of hepatic progenitor cells in mice.

UNLABELLED: Hepatocytes possess a remarkable capacity to regenerate and reconstitute the parenchyma after liver damage. However, in the case of chronic injury, their proliferative potential is impaired and hepatic progenitor cells (HPCs) are activated, resulting in a ductular reaction known as oval cell response. Proapoptotic and survival signals maintain a precise balance to spare hepatocytes and progenitors from hyperplasia and cell death during regeneration. Survivin, a member of the family of inhibitor of apoptosis proteins (IAPs), plays key roles in the proliferation and apoptosis of various cell types. Here, we characterized the in vivo function of Survivin in regulating postnatal liver development and homeostasis using mice carrying conditional Survivin alleles. Hepatic perinatal loss of Survivin causes impaired mitosis, increased genome ploidy, and enlarged cell size in postnatal livers, which eventually leads to hepatocyte apoptosis and triggers tissue damage and inflammation. Subsequently, HPCs that retain genomic Survivin alleles are activated, which finally differentiate into hepatocytes and reconstitute the whole liver. By contrast, inducible ablation of Survivin in adult hepatocytes does not affect HPC activation and liver homeostasis during a long-life period. CONCLUSION: Perinatal Survivin deletion impairs hepatic mitosis in postnatal liver development, which induces HPC activation and reconstitution in the liver, therefore providing a novel HPC induction model.

Biomimetic HA-GO implant coating for enhanced osseointegration via macrophage M2 polarization-induced osteo-immunomodulation.

The pro-inflammatory/anti-inflammatory polarized phenotypes of macrophages (M1/M2) can be used to predict the success of implant integration. Hence, activating and inducing the transformation of immunocytes that promote tissue repair appears to be a highly promising strategy for facilitating osteo-anagenesis. In a previous study, titanium implants were coated with a graphene oxide-hydroxyapatite (GO-HA) nanocomposite via electrophoretic deposition, and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was found to be significantly enhanced when the GO content was 2wt%. However, the effectiveness of the GO-HA nanocomposite coating in modifying the in vivo immune microenvironment still remains unclear. In this study, the effects of GO-HA coatings on osteogenesis were investigated based on the GO-HA-mediated immune regulation of macrophages. The HA-2wt%GO nanocomposite coatings exhibited good biocompatibility and favored M2 macrophage polarization. Meanwhile, they could also significantly upregulate IL-10 (anti-inflammatory factor) expression and downregulate TNF-α (pro-inflammatory factor) expression. Additionally, the microenvironment, which was established by M2 macrophages, favored the osteogenesis of BMSCs both in vivo and in vitro. These findings show that the GO-HA nanocomposite coating is a promising surface-modification material. Hence, this study provides a reference for the development of next-generation osteoimmunomodulatory biomaterials.

Evaluation of salivary interleukin-17 and developmental endothelial locus-1 in patients with periodontitis with and without type 2 diabetes mellitus.

BACKGROUND: Bidirectional positive relationship between periodontitis and type 2 diabetes mellitus (T2DM) has been recognized, interleukin 17 (IL-17) and developmental endothelial locus-1 (Del-1) are proposed to play roles in periodontitis and T2DM. This study aims to investigate the association of IL-17 and Del-1 in patients with periodontitis with and without T2DM by measuring their salivary levels. METHODS: A total of 80 participants were enrolled in a cross-sectional study and divided into healthy (H, n = 27), periodontitis (P, n = 29) and periodontitis with diabetes (PDM, n = 24) groups based on their periodontal and diabetic examination results. Periodontal parameters (plaque index [PI], bleeding on probing [BOP], probing depth [PD], and clinical attachment level [CAL]) as well as diabetic parameters (fasting plasma glucose [FG] and glycated hemoglobin [HbA1c]) were documented and unstimulated saliva was collected. Salivary IL-1ß, active-matrix metalloproteinase-8 (aMMP-8), tumor necrosis factor-α (TNF-α), IL-6, IL-8, IL-17, and Del-1 were determined through enzyme-linked immunosorbent assay (ELISA) and their relationships with periodontal and diabetic parameters were examined. RESULTS: The periodontitis and periodontitis with diabetes groups showed significantly higher levels of IL-17 and lower levels of Del-1 compared with healthy group. The periodontitis with diabetes group exhibited higher levels of IL-17 and lower levels of Del-1 compared with the periodontitis group. After correlation analysis, there were significant correlations between salivary IL-17 and Del-1 and clinical parameters, IL-17 and Del-1 were correlated with PD (r = 0.36, -0.39, p < 0.01), CAL (r = 0.40, -0.42, p < 0.01) and BOP (r = 0.35, -0.37, p < 0.01), they were correlated with FG (r = 0.26, -0.25, p < 0.05) and HbA1c (r = 0.28, -0.40, p < 0.05). Positive relationships were observed between IL-17 and IL-1ß and between IL-17 and aMMP-8 (r = 0.80, 0.77, p < 0.01), while Del-1 exhibited negative correlations with IL-1ß and aMMP-8 (r = 0.59, 0.69 p < 0.01). Comparison between IL-17 and Del-1 confirmed an inverse relationship (r = -0.71, p < 0.01). Salivary Del-1 levels in the older group were lower compared with young group across the H, P and PDM groups, although these differences were not statistically significant (p > 0.05). CONCLUSIONS: Salivary IL-17 and Del-1 levels in the periodontitis with diabetes group showed significant changes compared with the periodontitis group, they exhibited an inverse relationship and were both correlated with periodontal parameters (PD, CAL, and BOP) and diabetic parameters (FG and HbA1c). PLAIN LANGUAGE SUMMARY: Periodontitis and type 2 diabetes mellitus (T2DM) are two common diseases all over the world, some inflammatory mediators (interleukin 17 [IL-17] and developmental endothelial locus-1 [Del-1]) regulate neutrophil production, recruitment and clearance when the body becomes infected and believed to be involved in the progress of diseases of periodontitis and diabetes. In this study, we enrolled healthy subjects, patients with periodontitis, patients with periodontitis and diabetes. We performed dental examinations and evaluated their blood glucose levels, collected their saliva, and detected IL-17 and Del-1 levels in their saliva. We found both patients with periodontitis and patients with periodontitis and diabetes showed higher IL-17 levels and lower Del-1 levels compared with healthy subjects. Patients with periodontitis and diabetes showed higher IL-17 levels and lower Del-1 levels compared with patients with periodontitis. Salivary IL-17 and Del-1 levels were both correlated with dental examination results and blood glucose levels, and salivary IL-17 and Del-1 displayed an inverse relationship.

Toonanoronoids A-E, five new limonoids from Toona ciliata var. yunnanensis.

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.

Digital measurement of deciduous tooth dimensions in China: A cross-sectional survey.

OBJECTIVE: Crown dimensions data of deciduous teeth hold anthropological, forensic, and archaeological value. However, such information remains scarce for the Chinese population. This multi-center study aimed to collect a large sample of deciduous crown data from Chinese children using three-dimensional measurement methods and to analyze their dimensions. DESIGN: A total of 1592 children's deciduous dentition samples were included, and the sample size was distributed according to Northeast, North, East, Northwest, Southwest and South China. Digital dental models were reconstructed from plaster dental models. Independent sample t test, paired t test, principal component analysis (PCA), and factor analysis (FA) were used to analyze the tooth crown dimensions. RESULT: 18,318 deciduous teeth from 1592 children were included. Males exhibited slightly larger values than females. The range of sexual dimorphism percentages for each measurement was as follows: mesiodistal diameter (0.40-2.08), buccolingual diameter (0.13-2.24), and maxillogingival diameter (0.48-3.37). The FA results showed that the main trend of crown dimensions changes was the simultaneous increase or decrease in mesiodistal diameter, buccolingual diameter and maxillogingival diameter in three directions. CONCLUSION: This is the first large-scale survey of deciduous tooth crown dimensions in China, which supplements the data of deciduous tooth measurement and provides a reference for clinical application.

A G protein-biased ligand at the µ-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine.

The concept of ligand bias at G protein-coupled receptors broadens the possibilities for agonist activities and provides the opportunity to develop safer, more selective therapeutics. Morphine pharmacology in ß-arrestin-2 knockout mice suggested that a ligand that promotes coupling of the µ-opioid receptor (MOR) to G proteins, but not ß-arrestins, would result in higher analgesic efficacy, less gastrointestinal dysfunction, and less respiratory suppression than morphine. Here we report the discovery of TRV130 ([(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl})amine), a novel MOR G protein-biased ligand. In cell-based assays, TRV130 elicits robust G protein signaling, with potency and efficacy similar to morphine, but with far less ß-arrestin recruitment and receptor internalization. In mice and rats, TRV130 is potently analgesic while causing less gastrointestinal dysfunction and respiratory suppression than morphine at equianalgesic doses. TRV130 successfully translates evidence that analgesic and adverse MOR signaling pathways are distinct into a biased ligand with differentiated pharmacology. These preclinical data suggest that TRV130 may be a safer and more tolerable therapeutic for treating severe pain.

Interference of ALOX5 alleviates inflammation and fibrosis in high glucose­induced renal mesangial cells.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD), seriously threatening the health of individuals. The 5-lipoxygenase (ALOX5) gene has been reported to be associated with diabetes, but whether it is involved in DN remains unclear. The present study aimed to explore the role of ALOX5 in DN and to clarify the potential mechanism. Mouse renal mesangial cells (SV40 MES-13) were treated with high glucose (HG) to mimic a DN model in vitro. The expression level of ALOX5 was assessed using reverse transcription-quantitative PCR and western blotting. Cell Counting Kit-8 and flow cytometric assays were performed to determine cell proliferation, the cell cycle and apoptosis. Immunofluorescence was carried out to detect the expression of Ki67 and proliferating cell nuclear antigen (PCNA). The inflammatory cytokines were assessed using ELISA. The expression of fibrosis- and NF-κB-related proteins was determined using western blotting. The results revealed that ALOX5 was significantly upregulated in HG-induced SV40 MES-13 cells. Interference of ALOX5 greatly hindered HG-induced cell viability loss, as well as increasing the expression of Ki67 and PCNA. In addition, HG induced cell cycle arrest in the G1 phase and cell apoptosis, which were then partly abolished by interference of ALOX5. Moreover, the elevated production of inflammatory cytokines and upregulated fibrosis-related proteins induced by HG were weakened by interference of ALOX5. Eventually, interference of ALOX5 was found to reduce the activity of NF-κB signaling in HG-induced SV40 MES-13 cells. Collectively, interference of ALOX5 serves as a protective role in HG-induced kidney cell injury, providing a potential therapeutic strategy of DN treatment.

The role of PRX1-expressing cells in periodontal regeneration and wound healing.

The ideal outcome of wound healing is the complete restoration of the structure and function of the original tissue. Stem cells are one of the key factors in this process. Currently, the strategy of periodontal regeneration based on mesenchymal stem cells (MSCs) is generally used to expand stem cells in vitro and then transplant them in vivo. However, their clinical application is limited. In fact, the human body has the capacity to regenerate through stem cells residing in different tissues, even without external therapeutic intervention. Stem cell niches are present in many adult tissues, such as the periodontal ligament and gingiva, and stem cells might remain in a quiescent state in their niches until they are activated in response to a regenerative need. Activated stem cells can exit the niche and proliferate, self-renew, and differentiate to regenerate original structures. Thus, harnessing the regenerative potential of endogenous stem cells in situ has gained increasing attention as a simpler, safer, and more applicable alternative to stem cell transplantation. Nevertheless, there are several key problems to be solved in the application of periodontal mesenchymal stem cells. Thus, animal studies will be especially important to deepen our knowledge of the in vivo mechanisms of mesenchymal stem cells. Studies with conditional knockout mice, in which the expression of different proteins can be eliminated in a tissue-specific manner, are especially important. Post-natal cells expressing the paired-related homeobox protein 1 (PRX1 or PRRX1), a transcription factor expressed in the mesenchyme during craniofacial and limb development, have been shown to have characteristics of skeletal stem cells. Additionally, following wounding, dermal Prx1+ cells are found out of their dermal niches and contribute to subcutaneous tissue repair. Postnatal Prx1+ cells are uniquely injury-responsive. Meanwhile, current evidence shows that Prx1+ cells contribute to promote dentin formation, wound healing of alveolar bone and formation of mouse molar and periodontal ligament. Initial result of our research group also indicates Prx1-expressing cells in bone tissue around the punch wound area of gingiva increased gradually. Collectively, this review supports the future use of PRX1 cells to stimulate their potential to play an important role in endogenous regeneration during periodontal therapy.

LDER: a classification framework based on ERP enhancement in RSVP task.

Objective.Rapid serial visual presentation (RSVP) based on electroencephalography (EEG) has been widely used in the target detection field, which distinguishes target and non-target by detecting event-related potential (ERP) components. However, the classification performance of the RSVP task is limited by the variability of ERP components, which is a great challenge in developing RSVP for real-life applications.Approach.To tackle this issue, a classification framework based on the ERP feature enhancement to offset the negative impact of the variability of ERP components for RSVP task classification named latency detection and EEG reconstruction was proposed in this paper. First, a spatial-temporal similarity measurement approach was proposed for latency detection. Subsequently, we constructed a single-trial EEG signal model containing ERP latency information. Then, according to the latency information detected in the first step, the model can be solved to obtain the corrected ERP signal and realize the enhancement of ERP features. Finally, the EEG signal after ERP enhancement can be processed by most of the existing feature extraction and classification methods of the RSVP task in this framework.Main results.Nine subjects were recruited to participate in the RSVP experiment on vehicle detection. Four popular algorithms (spatially weighted Fisher linear discrimination-principal component analysis (PCA), hierarchical discriminant PCA, hierarchical discriminant component analysis, and spatial-temporal hybrid common spatial pattern-PCA) in RSVP-based brain-computer interface for feature extraction were selected to verify the performance of our proposed framework. Experimental results showed that our proposed framework significantly outperforms the conventional classification framework in terms of area under curve, balanced accuracy, true positive rate, and false positive rate in four feature extraction methods. Additionally, statistical results showed that our proposed framework enables better performance with fewer training samples, channel numbers, and shorter temporal window sizes.Significance.As a result, the classification performance of the RSVP task was significantly improved by using our proposed framework. Our proposed classification framework will significantly promote the practical application of the RSVP task.

Comprehensive Analysis of the Mechanism of Periodontitis-Related mRNA Expression Combined with Upstream Methylation and ceRNA Regulation.

Background: Periodontitis is a multifactorial disease mainly caused by the formation of plaque biofilm, which can lead to the gradual destruction of tooth-supporting tissues. Current research on the genetics and epigenetics of periodontitis remains relatively limited, and the molecular mechanisms remain largely unknown. Objective: Our aims were to construct competitive endogenous RNA (ceRNA) network and determine DNA methylation patterns of target genes to help elucidate the pathogenesis of periodontitis. Methods: We analyzed the expression profiles of the GSE16134, GSE54710, GSE10334, and GSE59932 datasets from the Gene Expression Omnibus database through the weighted gene coexpression network analysis system and screened mRNAs that are regulated by the level of methylation and are associated with the occurrence of periodontitis. Next, a lncRNA-miRNA-mRNA ceRNA network was constructed using databases including miRanda and TargetScan. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted for genes in the clinically significant modules. Finally, a protein-protein interaction network was built. Results: We finally identified four mRNAs, four miRNAs, and six lncRNAs as shared differentially expressed genes related to the periodontitis inflammation pathway. IL-6, IFNA17, CXCL12, and TNFRSF13C were identified as key genes whose expression was significantly enriched in the nuclear factor κB and TLR4 pathways. Moreover, the expression of 28 genes were downregulated by hypermethylation and 70 genes were upregulated by hypomethylation. Conclusions: The constructed ceRNA network can improve our understanding of the pathogenesis of periodontitis. Candidate mRNAs from the ceRNA network could serve as new therapeutic targets and prognostic biomarkers in periodontitis.

Association between CYP2B6 c.516G >T variant and acute leukaemia: A protocol for systematic review and meta-analysis.

BACKGROUND: Acute leukemia (AL) is a kind of malignant tumor of hematopoietic system. A number of studies have suggested that Single Nucleotide Polymorphisms are significantly associated with risk of AL. Present study performs meta-analysis to evaluate the association between CYP2B6 c.516G>T variant and AL risk. METHODS: Databases including PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang were searched for literatures to September 30, 2019, both in English and Chinese. Relative risk and its 95% confidence intervals were used to assess the associations. Statistical analyses of this meta-analysis were conducted by using STATA 13.0. software. RESULTS: A total of 7 studies, including 1038 cases and 1648 controls, were analyzed. Our results indicated that CYP2B6 c.516G>T variant was significantly related to an increased the risk of AL under dominant model, recessive model, homozygote model, and allelic model. In addition, subgroup analyses were also performed by disease classification, country, and study design. No significant associations were obtained between CYP2B6 c.516G>T variant and the risk of AL under the recessive model in the design of hospital-based (relative risk = 0.98; 95% confidence interval: 0.95-1.01; P  = 0.118). CONCLUSION: Our meta-analysis indicated that the CYP2B6 variant is significantly associated with AL risk, in which CYP2B6 c.516G>T is related to an increased risk of AL.