As a dioxygenase, Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (5hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities.
5-Methylcytosine ; analogs & derivatives ; chemistry ; metabolism ; Animals ; Cell Differentiation ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; DNA-Binding Proteins ; physiology ; Genome ; Genomics ; Mice ; Mice, Knockout ; Osteoclasts ; cytology ; metabolism ; Proto-Oncogene Proteins ; physiology

Objective To investigate the efficacy of the infrared ultrashort wave treatment of abdominal incision in-fection. Methods Chose 70 cases of patients with abdominal incision infection, and they were divided into 2 groups randomly, which using systemic anti infection and dressing the same incision replacement. The treatment group used the infrared irradiation to the wound in the morning, while in the afternoon using ultrashort wave therapy with high power. The control group did not use physical therapy. Two groups treat infection control granulation tissue to II period when fresh debridement suture of incision, the treatment group continue to therapy until incision healing. Results Treatment group of incision healing days was (15.26±5.14) d; The control group incision healing days was (21.74±5.35)d. The two groups had significant difference (P<0.01). Conclusion Infrared ultrashort wave treatment of abdominal incision infection can significantly reduce the incision healing of the number of days, curative effect is good and simple, which easy to reduce health care costs.

Objective To explore brain activity features during the resting state in alcohol dependent individuals,and study the relationship between the brain activity features and alcohol dependent individuals' clinical symptoms.Methods Twenty-four alcohol dependent individuals and 22 healthy control subjects,well matched in gender,age,education and handedness,were enrolled as the alcohol dependent group and control group respectively.AGE 3.0 T MR scanner was used to acquire all the subjects' resting state data. DPARSF software was used to process resting functional MRI data,and then the whole brain fractional amplitudes of low frequency fluctuation (fALFF) data were acquired.Two-sample t test statistical analysis was made to access fALFF difference between the two groups. Results In comparison with the control group,the alcohol dependent group showed reduced fALFF in bilateral medial prefrontal gyrus,right inferior occipital gyrus,left precuneus,left inferior temporal gyrus,and left posterior lobe of cerebellum (0.64-1.69 vs.0.87-1.78,t =- 4.23- - 2.79,P ＜ 0.05 ). fALFF was increased in the alcohol dependent group at the anterior cingulate,bilateral inferior frontal gyrus,right middle frontal gyrus,bilateral insular lobe,bilateral dorsal thalamus ( 0.86-1.82 vs. 0.76-1.58,t =3.56-3.96,P ＜ 0.05 ).Conclusion Alcohol dependent individuals had abnormal activity at the bilateral prefrontal lobe,anterior cingulate,bilateral dorsal thalamus,bilateral insular lobe,left posterior lobe of cerebellum et al,during the resting state,and these abnormal activities might be related with clinical manifestation and pathophysiology.

OBJECTIVETo investigate the suppressive effect of resveratrol on growth of U251 human glioma cells and its correlated mechanism.

METHODU251 human glioma cells were treated with resveratrol at various concentrations, MTT assay was used to determine the inhibitory rate of cell proliferation, FCM to detect the cell apoptosis, the expressions of Bcl-2, Bcl-XL, STAT3 and CyclinD1 were analysed by immunohistochemistry and Western blot to examine the expression of Bcl-2, Bcl-XL, STAT3, CyclinD1, Caspase-3 and Bax.

RESULTAfter treatment with resveratrol, MTT assay showed the growth of U251 cells was inhibited in dose-dependent and time-dependent manners, apoptosis of cells advanced stage was built up, immunohistochemical staining displayed decreased the expression of Bcl-2, Bcl-XL, STAT3 and CyclinD1 and Western blot showed that resveratrol decreased the expression of Bcl-2, Bcl-XL, STAT3 and CyclinD1, and built up Bax and Caspase-3.

CONCLUSIONIt is possible that downregulated the expression of Bcl-2, Bcl-XL, but upregulated Bax and Caspase-3, and the indication was obviously in dose-dependent and time-dependent manners.

Apoptosis ; drug effects ; Blotting, Western ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cyclin D1 ; metabolism ; Gene Expression Regulation, Neoplastic ; drug effects ; Glioma ; drug therapy ; metabolism ; Humans ; Immunohistochemistry ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; STAT3 Transcription Factor ; metabolism ; Stilbenes ; therapeutic use ; bcl-2-Associated X Protein ; metabolism ; bcl-X Protein ; metabolism