ABSTRACT
Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.
ABSTRACT
Objective:To investigate the wear characteristics of bovine enamel and lithium disilicate glass ceramic under simulated oral environment.Methods:18 cylindrical lithium disilicate glass-ceramic specimens with the length of 8 mm and diameter of 3 mm were randomly divided into 2 groups (n =9),9 lithium disilicate glass-ceramic specimens and 9 bovine enamel specimens were served as the antagonists respectively.The specimens were then loaded in a wear simulator and subjected to friction force of 10 N for 540 000 cycles in artificial saliva and room temperature(speed 100 r/min,turning radius of 2.5 mm,uniform circular motion) condition.During the testing,10 checkpoints were applied to measure the height loss of the specimens with 3D profilometer,then wear curves were plotted.Scanning electron microscopy were applied to investigate the worn surfaces at different wear stages.Results:At every checkpoints,bovine enamel wear height loss was larger than the lithium disilicate specimens (P ＜ 0.05);bovine enamel wear curve exhibits a runningin period,steady wear period and severe wear period 3 stages of wear,while wear curves of lithium disilicate glass ceramics exhibit onlyrunning-in period and steady wear period 2 wear stages.Both groups had the corresponding micro-morphological features in different periods.Conclusion:Bovine enamel and lithium disilicate glass ceramics show a phase dynamic evolution law under the simulated oral environment.Bovine enamel is more susceptible to wear than lithium disilicate,suggesting that clinical attention should be paid to prevent the excessive wear of natural teeth caused by lithium disilicate glass ceramic restorations.
ABSTRACT
The implant prosthesis has been extensively used in clinic recently, and implant failure is appearing. Many factors may cause the failure, and they work together generally. This paper summarizes and analyzes the failure cases related to implant treatment and relevant risk factors of oral implants in Department of Implantation, School of Stomatology, The Fourth Military Medical University during the past six years, in order to improve the success rate of implant prosthesis and provide guidance for clinical application.
ABSTRACT
BACKGROUND:Our previous studies have shown that mesenchymal stem cells play an immunomodulatory role in Th17 cells, but the mechanism of action remains to be elucidated, therefore, to explore the role of Tol-like receptor 1 in which wil provide possible experimental basis for the future potential of celltherapy strategies. OBJECTIVE:To investigate the role of Tol-like receptor 1 in the immunoregulatory function of mesenchymal stem cells on Th17 cells. METHODS:Separation of adherent bone marrow-derived human embryonic sources of mesenchymal stem cells, immunomagnetic separation of normal CD4+T cells. CD4+T cells were cultured alone or in combination with mesenchymal stem cells co-cultured 4d. Real-time quantitative polymerase chain reaction assay interleukin-17, Tol-like receptor 1 expression levels related genes;number of Th17 cells by flow cytometry. Bone marrow mesenchymal stem cells from human embryos were separated using adherence method, and co-cultured with human CD4+T cells from healthy donors using immunomagnetic separation method for 4 days. The expression of interleukin-17 and Tol-like receptor 1 mRNA was detected by real-time PCR, and the number of Th17 cells was observed by flow cytometry. RESULTS AND CONCLUSION:Tol-like receptor 1 mRNA was expressed in both CD4+T cells and mesenchymal stem cells. Level of interleukin-17 mRNA was significantly higher in mesenchymal stem cells co-cultured with CD4+T cells than in CD4+T cells cultured alone (relative value 3.59±0.11 vs. 1.14±0.08, P<0.01). Consistent with the expression of interleukin-17 mRNA, increased level of Tol-like receptor 1 mRNA was detected in mesenchymal stem cells co-cultured with CD4+T cells compared with CD4+T cells cultured alone (relative value 6.07±1.79 vs. 1.53±0.63, P<0.01). Furthermore, Flow cytometry analysis showed that the percentage of Th17 cells in the mesenchymal stem cells co-cultured with CD4+T cells was significantly higher than that in CD4+T cells cultured alone, (4.53±1.27)%vs. (2.39±0.80)%(P<0.01). Tol-like receptor 1 might be involved in the immunoregulatory regulation of Th17 cells by mesenchymal stem cells.
ABSTRACT
BACKGROUND:Previous studies have found that embryonic bone marrow mesenchymal stem cel s can promote human Th17 cel proliferation, but the inherent regulatory mechanisms stil need to be elucidated. OBJECTIVE:To investigate the role of Tol-like receptor 3 in the immunoregulation of Th17 cel s by mesenchymal stem cel s. METHODS:Human CD4+T cel s from healthy donors were isolated by immunomagnetic bead method, and then cultured alone or co-cultured with embryonic bone marrow mesenchymal stem cel s for 4 days. The mRNA expression level of interleukin-17, Tol-like receptor 3 and MyD88 was detected by real-time PCR. RESULTS AND CONCLUSION:Compared with CD4+T cel cultured alone group, the mRNA level of interleukin-17 was significantly higher in the co-culture group (3.59±0.11 vs. 1.14± 0.08, P<0.01). Consistent with the expression of interleukin-17 mRNA, increased level of Tol-like receptor 3 mRNA was detected in the co-culture group compared with the CD4+T cel cultured alone group (3.10±1.60 vs. 0.94± 0.01, P<0.05). Furthermore, MyD88 in the co-culture group was significantly higher than that in CD4+T cel cultured alone group (2.29±0.05 vs. 1.85±0.31, P<0.01). Tol-like receptor 3 may be involved in the immunoregulation of Th17 cel s by embryonic bone marrow mesenchymal stem cel s, which provides experimental evidence for potential cel therapeutic strategy.