Epigenetic Modulation on Tau Phosphorylation in Alzheimer's Disease.

Tau hyperphosphorylation is a typical pathological change in Alzheimer's disease (AD) and is involved in the early onset and progression of AD. Epigenetic modification refers to heritable alterations in gene expression that are not caused by direct changes in the DNA sequence of the gene. Epigenetic modifications, such as noncoding RNA regulation, DNA methylation, and histone modification, can directly or indirectly affect the regulation of tau phosphorylation, thereby participating in AD development and progression. This review summarizes the current research progress on the mechanisms of epigenetic modification associated with tau phosphorylation.

Overexpressing Runx2 of BMSCs Improves the Repairment of knee Cartilage Defects.

BACKGROUND: Recruitment of gene modifying bone marrow mesenchymal stem cells (BMSCs) has been considered an alternative to single-cell injection in articular cartilage repair. PURPOSE: This study aimed to investigate whether the effect of runt-related transcription factor 2(Runx2) overexpression bone marrow mesenchymal stem cells in vivo could improve the quality of repaired tissue of a knee cartilage defect in a rabbit model. METHODS: Thirty-two New Zealand rabbits were randomly divided into four groups. The blank group (Con) did not receive anything, the model group (Mo) was administered saline, the simple stem cell group (MSCs) received MSCs injection, and the Runx2 transfection group (R-MSCs) received Runx2 overexpression MSCs injection. After adapting to the environment for a week, a 5 mm diameter cylindrical osteochondral defect was created in the center of the medial femoral condyle. Cell and saline injections were performed in the first and third weeks after surgery. The cartilage repair was evaluated by macroscopically and microscopically at 4 and 8 weeks. RESULTS: Macroscopically, defects were filled and surfaces were smoother in the MSCs groups than in the Mo group at 4th week. Microscopically, the R-MSCs group showed coloration similar to surrounding normal articular cartilage tissue at 8 weeks in masson trichrome staining. The COL-II, SOX9, and Aggrecan mRNA expressions of MSCs were enhanced at 4 weeks compared with R-MSCs, then the expression reduced at 8 weeks, but was still higher than Mo group level (P<0.05). The western blot examination revealed that the COL-IIand SOX9 expression of MSCs was higher than R-MSCs at 4 weeks, then the expression reduced at 8 weeks, but was still higher than the Mo level (P<0.05). The IL-1ß content in the joint fluid also revealed that cartilage repair with R-MSCs was better than that with MSCs at 8 weeks (P<0.05). CONCLUSION: The R-MSCs group showed cellular morphology and arrangement similar to surrounding normal articular cartilage tissue, and Runx2 overexpression of MSCs resulted in overall superior cartilage repair as compared with MSCs at 8 weeks.

ß­ecdysterone protects against apoptosis by promoting autophagy in nucleus pulposus cells and ameliorates disc degeneration.

Increasing cell apoptosis is one of the major causes of intervertebral disc degeneration (IDD). ß-ecdysterone has been demonstrated to protect PC12 cells against neurotoxicity. A previous study revealed that ß­ecdysterone may be involved in the regulation of autophagy in osteoblasts. Therefore, we hypothesized that ß­ecdysterone may possess therapeutic effects on IDD via autophagy stimulation. The effect of ß­ecdysterone on IDD was explored by in vitro experiments. The results demonstrated that ß­ecdysterone attenuated the apoptosis induced by tert­butyl hydroperoxide via promoting autophagy in nucleus pulposus cells. Beclin­1, an indispensable protein for the stimulation of autophagy, is upregulated and stabilized by ß­ecdysterone in a dose­ and time­dependent manner in nucleus pulposus cells. Inhibition of autophagy with 3­methyladenine partially abrogated the protective function of ß­ecdysterone against apoptosis of nucleus pulposus cells, indicating that autophagy participated in the protective effect of ß­ecdysterone on IDD. Additionally, ß­ecdysterone promoted the expression of anabolic genes while inhibiting the expression of catabolic genes in nucleus pulposus cells. Collectively, the present study demonstrated that ß­ecdysterone may protect nucleus pulposus cells against apoptosis by autophagy stimulation and ameliorate disc degeneration, which indicates that ß­ecdysterone may be a potential therapeutic agent for IDD.

[Panlongqi tablet (Chinese characters) combined with lumbar facet joint release for the treatment of lumbar spinal stenosis of Fengshi Bizu (Chinese characters)].

OBJECTIVE: To investigate the clinical efficacy of Panlongqi tablet (Chinese characters) combined with lumbar facet joint release for lumbar spinal stenosis of type Fengshi Bizu (Chinese characters). METHODS: Since February 2012 to February 2013, 120 patients with lumbar spinal stenosis of Fengshi Bizu (Chinese characters) syndrome were retrospectively studied. According to different treatment methods, 120 patients with lumbar spinal stenosis were divided into Panlongqi tablet (Chinese characters)group and control groups, respectively. In Panlongqi tablet (Chinese characters)group, 60 patients were treated by Panlongqi tablet (Chinese characters) combined with lumbar facet joints release solution including 26 males and 34 females with an average age of (60.40±3.36) years old ranging from 46 to 65 ; the course of the disease was 2 to 15 years (averaged 7.6 years). In control group the other 60 patients were treated with lumbar facet joint release including 24 males and 36 females with an average age of (61.20±2.47) years old ranging from 48 to 63; the course was 3 to 14 years (averaged 6.9 years). The clinical effect of patients were evaluated by JOA and ODI score before treatment, at 4 weeks and 3 months after treatment. RESULTS: All patients were followed up for 4 to 7 months (means 5.6 months). After 3 months,7 cases in control group recurrenced symptoms,only 1 case in Panlongqi tablet (Chinese characters) group recurrenced. At 4 weeks and 3 months of follow-up, ODI score and JOA score of Panlongqi tablet group were much better than those of the control group. CONCLUSION: For lumbar spinal stenosis of type Fengshi Bizu (Chinese characters),which were treated with lumbar facet joint release with Panlongqi tablet(Chinese characters), supplemented by back muscle exercise, in relieving waist and low back pain symptoms and improving functional status of lower lumbar spine, can obtain satisfactory clinical outcome, is a good method of conservative treatment for such diseases.