Secondary hyperuricemia in chronic renal failure promotes vascular calcification in rats / 生理学报

The present study was aimed to explore the effects of hyperuricemia on vascular calcification in chronic renal failure (CRF) and the mechanisms. Adenine diet-induced CRF rat model was used. Twenty-three male 8-week-old Wistar rats were randomly divided into control group (Ctr, n = 5), CRF group (n = 8) and CRF plus allopurinol group (CRF + ALL, n = 10), and the rats were given standard diet plus standard drinking water, adenine diet plus standard drinking water and adenine diet plus allopurinol drinking for 6 weeks, respectively. Vascular calcification of abdominal aorta was identified by o-cresolphthalein complexone copper assay and Von Kossa staining. The mRNA expression levels of osteogenic/chondrogenic regulatory factors (Cbfα1, Msx2, Osx, and Sox9), vascular smooth muscle cell (VSMC) lineage markers (SM22a and Acta2) and calcification inhibitors (Mgp and Opn) were detected by real-time PCR. The results showed that the levels of serum phosphorus (Pi), urea nitrogen, creatinine and uric acid were significantly increased in the CRF rats, whereas allopurinol reversed the levels of serum urea nitrogen, creatinine and uric acid, except for serum Pi. The calcium content of rat abdominal aorta in the CRF group was significantly higher than that of the Ctr group (P < 0.05), but it was partially rescued in the CRF + ALL group (P < 0.05); Compared with the Ctr group, Cbfα1, Msx2, Osx and Sox9 mRNA levels of abdominal aorta in the CRF group were significantly up-regulated, while SM22a, Acta2, Mgp and Opn mRNA levels were down-regulated. In the CRF + ALL group, the changes of Msx2, Osx, SM22a and Opn mRNA levels were reversed (P < 0.05). Allopurinol had no effect on high Pi-induced VSMC calcification, and uric acid (6 and 7 mg/dL) significantly increased high Pi-induced VSMC calcification in vitro (P < 0.05). These results suggest that hyperuricemia in CRF may promote the osteoblast/chondrocyte-like cells differentiation of VSMC and further exacerbate vascular calcification.

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.

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.