ABSTRACT
OBJECTIVES@#To observe the effect of type 2 diabetes mellitus (T2DM) on mandibular bone regeneration and the expression of factors related to T helper cell 17 (Th17 cell) and regulatory T cell (Treg cell) in mice.@*METHODS@#Thirty-six 6-week-old C57BL/6J male mice were randomly divided into normal control (NC) and T2DM groups. Fasting blood glucose levels were detected 0 d, 7 d, 14 d, and 28 d after surgery for mandibular defects. Hematoxylin-eosin (HE) staining was used in observing the bone after 7 d, 14 d, and 28 d of the healing process. Immunohistochemical staining was used in observing the expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), forkhead box protein P3 (Foxp3), retinoic acid related orphan receptor gamma T (RORγt), and protein tyrosine phosphatase non-receptor type 2 (PTPN2) after 7 d, 14 d, and 28 d of healing.@*RESULTS@#HE staining showed that the area with new bones in the T2DM group was significantly smaller than that in the NC group. Immunohistochemical staining showed that the expression of osteogenesis related proteins ALP and RUNX2 were significantly reduced in the T2DM group. In addition, the number of RORγt positive cells increased, whereas the number of Foxp3 positive cells and the expression PTPN2 decreased significantly in the mandibular bone defect in mice with T2DM.@*CONCLUSIONS@#T2DM significantly inhibit mandibular bone regeneration in mice. Decline in PTPN2 expression and the transition of Treg and Th17 may be the underlying molecular mechanisms.
Subject(s)
Animals , Male , Mice , Bone Regeneration , Diabetes Mellitus, Type 2 , Forkhead Transcription Factors , Mice, Inbred C57BL , TCF Transcription Factors , Th17 CellsABSTRACT
Objective: To investigate the potential role of human cytomegalovirus lower matrix phosphoprotein 65 (HCMV-pp65) in murine systemic lupus erythematosus (SLE). Methods: The prokaryotic plasmid pET-28b-pp65 was constructed to express the HCMVpp65 protein. BXSB mice and C57BL/6 mice were inoculated with pp65 eukaryotic plasmid pcDNA3.0-pp65 intramuscularly 5 times at 2-week intervals, and then the blood of the mice was subsequently collected via the retro-orbital vein. Indirect ELISAs were used to evaluate the concentration of anti-pp65 immunoglobulin G, anti-double-stranded DNA and antinuclear antibodies. Interleukin-1β and tumor necrosis factor-α were also determined by competitive ELISA. At the same time, 3 major SLE-related circulating microRNAs were examined by quantitative RT-PCR. Results: The early production of autoantibodies was observed in pp65-immunized male BXSB as well as C57BL/6 mice. Overexpression of interleukin-1β and tumor necrosis factor-α were detected in pp65-immunized male BXSB mice. Quantitative RT-PCR analyses showed that three SLE related microRNAs (microRNA-126, microRNA-125a, and microRNA-146a) were downregulated in peripheral blood mononuclear cells of pp65-immunized mice. Conclusions: Our findings indicate that HCMV-pp65 immunization strongly triggers the development and progression of SLE-like disease in both BXSB and C57BL/6 mice, which indicates that the immune responses induced by HCMV-pp65 may be involved in the development of SLE.
ABSTRACT
OBJECTIVE: Cationic polymers can deliver gene into brain and improve the impression of exogenous gene in brain tissues. This review elaborates the problems and strategies of cationic polymers tansfering gene into brain by cationic polymers, and provides a reference for further study. METHODS: The literatures about cationic polymers were searched, and the progress of cationic polymers as gene carrier from several aspects were analyzed and summarized such as vector construction, ligands modification, efficient improvement and toxicity reduction. RESULTS AND CONCLUSION: Cationic polymer vector has the advantage of high drug-loading, but it has to overcome the limits of BBB, high cell toxicity, low transfection and low targeting. It can be improved by structure reconstruction, ligand modification, and so on. Cationic polymer is relatively safe and high efficient, so it is capable of providing efficient approach of gene delivery.