Tet2 Regulates Osteoclast Differentiation by Interacting with Runx1 and Maintaining Genomic 5-Hydroxymethylcytosine (5hmC) / 基因组蛋白质组与生物信息学报·英文版

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.

Comparison of the application of three different methods in the diagnosis of early diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To compare and analyze the diagnostic value of iris fluorescein angiography (IFA) combined with fundus fluorescein angiography (FFA),indocyanine green angiograph (ICGA),fundus fluorescein angiography in the diagnosis of early diabetic retinitis (DR).METHODS:Totally 70 patients (136 eyes) with early diabetic retinopathy enrolled in our hospital from August 2015 to August 2016 were selected in this study.All patients were respectively treated with ICGA,FFA and IFA+FFA,and the detection results of three kinds of imaging methods were analyzed.RESULTS:There were 120 pathological eyes (88.2％)were detected by FFA,124 pathological eyes (91.2％)were detected by ICGA,130 pathological eyes (95.6％)were detected by IFA+ FFA,and there was no significant difference in the detection rate between the three methods (P＞0.05).FFA detected 48 eyes with neovascularization,18 eyes with vitreous hemorrhage,38 eyes with macular edema,16 eyes without perfusion area;ICGA detected 49 eyes with neovascularization,38 eyes with macular edema,17 eyes with vitreous hemorrhage,20 eyes without perfusion area;IFA+ FFA detected 17 eyes with proliferative diabetic iridopathy (DI),22 eyes with non-proliferative DI,5 eyes with NVG,92 eyes without DI.CONCLUSION:In the diagnosis of early diabetic retinopathy,iris fluorescence angiography,fundus fluorescein angiography and indocyanine green angiography all have good diagnostic value,but IFA+FFA can detect the diabetic retinopathy in time and provide the help for the timely treatment.

Role of Histone Methylation in Myeloid Malignancies -Review / 中国实验血液学杂志

Histone methylation is one of the important epigenetic regulatory mechanisms, and plays a significant role in a variety of physiological and pathological processes. Many recent studies have shown that abnormalities of histone methylation are closely related with the initiation and progression of myeloid malignancies. The reversibility of histone methylation provides a broad prospect for the discovery and application of specific small molecule drugs. This review summarizes the recent progresses in this area and mainly focuses on the correlation of histone methylation with myeloid malignancies.

Research Advances in the Mutation of TET2 Gene in Myeloid Maligancies / 中国医学科学院学报

TET2 gene is a member of TET oncogene family. It has been reported as a tumor suppressor gene with important roles in myelopiesis. Recent studies have shown that TET2 protein takes part in demethylation by converting 5-methylcytosine (5-mc) into 5-hydroxymethylcytosine (5-hmc). Somatic TET2 inactivation leads to abnormal myelopiesis and myeloid malignancies. In this review,the structure and function of TET2 and the relationship between TET gene mutation and myeloid malignancies are summarized.

Anti-mouse CD122 antibody promotes the hematopoietic repopulating capacity of cord blood CD34⁺ cells in NOD/SCID mice / 中国实验血液学杂志

The study was aimed to investigate the effect of anti-mouse CD122 antibody on the hematopoietic repopulating capacity of cord blood CD34⁺ cells in a humanized murine model-non obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After sublethal irradiation with γ-ray, NOD/SCID mice were intraperitoneally injected with 200 µg mouse isotype control antibody or anti-mouse CD122 antibody. Human cord blood CD34⁺ cells or phosphate-buffered saline (PBS) were injected via the tail vein at 6-8 hours later. Cohort of the mice injected with anti-mice CD122 antibody or control antibody alone were sacrificed at different time point (at week 2, 3, and 4 weeks) after the injection, and the percentage of NK cells in the peripheral blood was analyzed by flow cytometry. To evaluate the effect of anti-mouse CD122 antibody on the repopulating capacity of cord blood CD34⁺ cells in the recipient mice, phenotype analysis was performed in the bone marrow at 6 and 8 weeks after the transplantation. The results showed that the proportion of NK cells in the peripheral blood were (4.6 ± 0.6)% and (5.7 ± 1.7)% at week 2 and 3 after anti-CD122 antibody injection respectively,which decreased by 60%, compared with the mice injected with isotype control antibody. After 6 and 8 weeks of cord blood CD34⁺ cell transplantation,the percentage of human CD45⁺ in the bone marrow of the recipient mice treated with anti-mice CD122 antibody was (63.0 ± 12.2)% and (53.2 ± 16.3)%,respectively,which were dramatically higher than that in the mice treated with isotype control antibody (7.7 ± 3.6)% and (6.1 ± 2.4)%. Moreover,at 8 weeks after transplantation,human CD34⁺ cells appeared significantly in the recipients treated with anti-CD122 antibody. It is concluded that the anti-mouse CD122 antibody enhances the hematopoietic repopulating capacity of cord blood CD34⁺ cells in the NOD/SCID mice through decreasing the proportion of NK cells.

Role of ASXL1 mutation in myeloid malignancies / 中国实验血液学杂志

Additional sex comb-like 1 ( ASXL1) is an enhancer of Trithorax and Polycomb family, which are necessary for the maintenance of stable repression of homeotic and other loci. Recently, alterations of ASXL1 gene were identified in the hematopoietic cells from patients with a variety of myeloid malignancies, including chronic myelomonocytic leukemia (CMML, 43% of cases), myelodysplastic syndrome (MDS, 20%), myeloproliferative neoplasms (MPN, 10%) and acute myeloid leukemia (AML, 20%). The majority of ASXL1 mutations are frameshift and nonsense mutations. These clinical data suggest an important role of ASXL1 in the pathogenesis and/or transformation of myeloid malignancies. However, the role of ASXL1 in the pathogenesis of myeloid malignancies and in normal hematopoiesis in vivo, as well as the underlying mechanisms remains unknown. This article reviews the structure and function of ASXL1, the clinical characteristic and prognostic significance of ASXL1 mutation, the association of ASXL1 with other gene mutation, as well as ASXL1 knock-down or silence in vitro and in vivo models.

Efficient isolation of mesenchymal stem cells from human bone marrow by direct plating method combined with modified primary explant culture / 中国实验血液学杂志

Human bone marrow is the major source of mesenchymal stem cells (MSC). It was reported that the standard density gradient centrifugation method was not efficient in isolating MSC and it may be caused by the existing of bone marrow particles. In previous study, a lot of MSC were obtained by culturing bone marrow particles alone combined with standard method. However, it is time- and labor-consuming to obtain bone marrow particles by filtering and to isolate MNC by density gradient centrifugation. This study was purposed to explore the more simple and efficient method to isolate MSC from bone marrow. Seven normal bone marrow aspirates were collected and centrifugated. The bone marrow particles floated on surface layers were cultured by modified primary explant culture, whereas the bone marrow aspirates deposited were cultured by direct plating method, then the immun phenotype and differentiation capability of isolated cells were analyzed. The results showed that in 3 of 7 aspirates, bone marrow particles were floated on surface layers, whereas the other bone marrow cells and some particles were deposited after centrifugation. The MSC were reliably isolated from the floating layers or deposited aspirates by modified primary explant culture and direct plating method separately. After 3 passages the isolated MSC did not express CD45 and CD34, but expressed CD105, CD73, CD44, CD90, CD49e and they could differentiate into chondrocytes and adipocytes. It is concluded that normal human bone marrow MSC can be isolated simply and efficiently by direct plating method in combination with modified primary explant culture.

Function of the present systematic evaluation in establishment of guidance for clinical practice / 中国针灸

<p><b>OBJECTIVE</b>Treatment of insomnia with acupuncture is taken as an example to explore the significance and problems existed in the present systematic evaluation in establishment of guidance for clinical practice.</p><p><b>METHODS</b>Fifteen articles on systematic evaluation of both English and Chinese were retrieved and studied carefully, their basic information was analyzed. Through study on the establishing process of the guidance of clinical practice, researches were focused on the possible significance of the articles to the guidance as well as the notes in the reuse of those articles since problem still existed.</p><p><b>RESULTS</b>It is held that the systematic evaluation has great significance on the establishment of the guidance from the aspects of applicable people, recommended standards of diagnosis and therapeutic evaluation, extended recommendation and methodology. Great importance should also be attached to the direct application of the research result and understanding of the evaluation result. The data should be rechecked when necessary.</p><p><b>CONCLUSION</b>Great guiding function can be found on the systematic evaluation of articles to the guidance. Moreover, if information needed to be taken into a full play, specific analysis should also be done on the concrete research targets.</p>