Research progress on histone acetylation/methylation in oral diseases / 口腔疾病防治

@#Histone acetylation and methylation can affect chromatin conformation and regulate a variety of biological activities. Abnormal histone acetylation and methylation modifications are related to the occurrence and development of a variety of oral diseases. Histone acetylation and methylation increase or decrease in an orderly manner to regulate the development of teeth. Fluoride ions can destroy the balance between histone acetylation and methylation, which may be related to the occurrence of dental fluorosis. In addition, histone acetylation and methylation are involved in the regulation of oral inflammatory diseases. In the inflammatory microenvironment, the expression of histone acetyltransferase GCN5 decreases, and the expression of Dickkopf 1 (DKK1) decreases, activating the Wnt/β-catenin pathway and ultimately inhibiting the osteogenic differentiation of periodontal ligament stem cells. Enhancer of zeste homolog 2 (EZH2) and H3K27me3 levels were decreased in inflamed dental pulp tissues and cells. EZH2 inhibition inhibited the expression of interleukin (IL)-1b, IL-6 and IL-8 in human dental pulp cells under inflammatory stimulation. Histone acetylation/methylation modifications can interact with multiple signaling pathways to promote the occurrence and development of oral tumors and are related to the high invasiveness of salivary gland tumors. Small molecule drugs targeting histone acetylation and methylation-related enzymes can regulate the level of histone methylation/acetylation and have shown potential in the treatment of oral and maxillofacial diseases. For example, the histone deacetylase inhibitor vorinostat can inhibit the secretion of inflammation-related cytokines; it also promotes the maturation of odontoblasts and the formation of dentin-related matrix, demonstrating its potential in pulp preservation. Understanding the role of histone acetylation/methylation modifications in the occurrence and development of oral diseases will help promote research on epigenetic modifications in oral diseases and provide new perspectives for disease diagnosis and treatment.

Recent advance in histone deacetylation in epilepsy pathogenesis and treatment / 中华神经医学杂志

Epilepsy is a complex neurological disease and its pathogenesis has not yet been clear. More and more evidence shows that epilepsy is closely related to epigenetic mechanisms such as histone deacetylation. Histone deacetylase inhibitors, a kind of epilepsy targeting drug potentially, are involved in the protection of neurogenesis and the regulation of a variety of neural signal cascade reactions. This article reviews the research progress of histone deacetylation in the pathogenesis of epilepsy and application prospect of histone deacetylase inhibitors in treating epilepsy.

Comparative evaluation of doxofylline and theophylline in patients of mild bronchial asthma.

Background: Asthma is common chronic disease worldwide. Methylxanthines has been used in the treatment of asthma. The study was undertaken to compare two Methylxanthines theophylline and doxofylline at doses recommended and commonly used in clinical practice in Mild Bronchial Asthma Patients. Methods: Study was conducted in patients of Mild Bronchial Asthma in TB and chest disease department of a medical college hospital. It was randomized, prospective and open label. A total of 107 patients were divided in two group .Group I was administered 400 mg theophylline SR once daily and group II was administered doxofylline 400 mg twice a day orally. Spirometric variables symptom score, and adverse effects were recorded on day 0, 7 and 21 of therapy. Data were compared and analysed using SPSS version 16. Results: Results of the study showed that there was significant improvement in spirometric variables and clinical symptom score compared to pretreatment values after medication in both groups on 7th and 21st days of treatment. But there was no statistically significant difference between improvement in theophylline and doxofylline groups with respect to spirometric variables and symptom score. There was no significant difference in two groups with respect to side effects (p>0.05). Conclusions: It is concluded in Patients of mild Bronchial Asthma Theophylline and doxofylline improve the spirometric and clinical symptoms and doxofylline has no advantage over theophylline in terms of either efficacy or safety on the doses commonly used in current clinical practice.

Scriptaid improves early development potential of mouse somatic cell nuclear transfer embryos / 中华神经医学杂志

Objective To examine the effect of Scriptaid,a histone deacetylase inhibitor and a kind of anti-cancer drug,on development of mouse somatic cell nuclear transfer (SCNT) embryos in vitro and explore a new strategy to improve the efficiency of SCNT. Methods SCNT was carried out by pizeo-activated micromanipulator in C57/BL6 mouse,from which the oocytes were chsoen as recipients and the cumulus cells as donors.The rcconstructcd embryos were randomly divided into 5 groups and activated in calcium-free activators with 0 mmol/L (negative control group),and 50,100,250 and 500 mmol/L Scriptaid for 6 h, respectively; and then, they were transferred into KSOM medium with corresponding concentrations of Scriptaid for 4 h.The cloned embryos were finally cultured in KSOM medium for 96 h.The development (form rate) of cloned embryos and the count of blastocysts cells were recorded. Results No significant differences on the activated rate of the reconstructed embryos and the 2-cell cleavage rate were noted between each 2 groups (P＞).05).However,the form rate (24.2％) and cell numbers (56.27±2.43) of blastocysts in 250 mmol/L Scriptaid activation group were significantlyhigher as compared with those in the negative control group, and 50, 100 and 500 mmol/L Scriptaid activation groups (form rates:5.3％,6.5％,9.4％ and 6.9％; cell numbers:44.67±1.53,50.25±1.26,52.33±2.50 and 50.75±1.50,respectively,P＜0.05). Conclusion The early development potential of mouse SCNT embryos in vitro can be dramatically improved by 250mmol/L Scriptaid.

Curcumin-induced Histone Acetylation in Malignant Hematologic Cells / 华中科技大学学报（医学）（英德文版）

This study investigated the inhibitory effects of curcumin on proliferation of hemato-logical malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacety-lation levels.The effects of curcumin and histone deacetylase inhibitor trichostatin A (TSA) on the growth of Raji cells were tested by MTT assay.The expression of acetylated histone-3 (H3) in Raji,HL60 and K562 cells,and peripheral blood mononuclear cells (PBMCs) treated with curcumin or TSA was detected by immunohistochemistry and FACS.The results showed curcumin inhibited pro-liferation of Raji cells significantly in a time- and dose-dependent fashion,while exhibited low toxic-ity in PBMCs.Curcumin induced up-regulation of the expression of acetylated H3 dose-dependently in all malignant cell lines tested.In conclusion,curcumin inhibited proliferation of Raji cells selec-tively,enhanced the level of acetylated H3 in Raji,HL60,and K562 cells,which acted as a histone deacetylase inhibitor like TSA.Furthermore,up-regulation of H3 acetylation may play an important role in regulating the proliferation of Raji cells.

Expression of Sodium/iodide Symporter Transgene in Neural Stem Cells / 대한핵의학회잡지

PURPOSE: The ability to noninvasively track the migration of neural progenitor cells would have significant clinical and research implications. We generated stably transfected F3 human neural progenitor cells with human sodium/iodide symporter (hNIS) for noninvasively tracking F3. In this study, the expression patterns of hNIS gene in F3-NIS were examined according to the cultured time and the epigenetic modulation. MATERIALS AND METHODS: F3 human neural stem cells had been obtained from Dr. Seung U. Kim (Ajou University, Suwon, Korea). hNIS and hygromycin resistance gene were linked with IRES (Internal Ribosome Entry Site) under control of CMV promoter. This construct was transfected to F3 with Liposome. To investigate the restoration of hNIS gene expression in F3-NIS, cells were treated with demethylating agent (5-Azacytidine) and Histone deacetylase inhibitor (Trichostatin A: TSA). The expression of hNIS was measured by I-125 uptake assay and RT-PCR analysis. RESULTS: The iodide uptake of the F3-NIS was higher 12.86 times than F3 cell line. According to the cell passage number, hNIS expression in F3-NIS gradually diminished. After treatment of 5-Azacytidine and TSA with serial doses (up to 20micro M, up to 62.5nM, respectively) for 24 hours, I-125 uptake and mRNA of hNIS in F3-NIS were increased. CONCLUSION: These results suggest that hNIS transfected F3 might undergo a change in its biological characters by cell passage. Therefore, the gene expression of exogenous gene transferred human stem cell might be affected to the epigenetic modulation such as promoter methylation and Histone deacetylation and to the cell culture conditions.

Trichostatin A inhances cytotoxic activity of antineoplastics on bladder caner cell T24 / 中国药理学通报

Aim To investigate the cytotoxic activity of HDAC inhibitor Trichostatin A (TSA)combined with anticancer drugs targeting DNA on T24 bladder cancer cell line.Methods MTT assay was used to detect the inhibitory rate of TSA alone or combined with ADM, MMC and DDP respectively on T24 bladder cancer cell in cancer cell proliferation by administering TSA alone or combined with ADM, MMC and DDP respectively.Jin′s equation was used to evaluate the efficacy of drug combination. Results The growth inhibitory rate of TSA combined with ADM, MMC and DDP respectively was in a concentration-dependent manner. The synergism of TSA combined with MMC was most significant. When administered in lower or moderate concentration, TSA combined with ADM or DDP in lower or moderate concentration demonstrated synergic effect too.Conclusion HDAC inhibitor TSA enhances the cytotoxic activity of anticancer drugs targeting DNA on bladder cancer cells and is promising to be used in chemotherapeutic regimens for advanced bladder cancer.