T cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia. However the poor prognosis and low morbidity restrict further analysis of the disease. Therefore there is an increasing demand to develop animal models for identifying novel therapeutic approaches. In this study, we inoculated the anti-mouse CD122 monoclonal antibody conditioned NOD/SCID mice with the leukemia cells from 9 T-ALL patients and 1 cell line via the tail vein. Four of the 9 patients and the cell line were successfully engrafted. Flow cytometry detected high percentage of human CD45(+) cells in recipient mice. Immunohistochemistry showed infiltration of human CD45(+) cells in different organs. Serial transplantation was also achieved. In vivo drug treatment showed that dexamethasone could extend survival, which was consistent with clinical observation. These results demonstrated that we successfully established 5 xenotransplantation models of T-ALL in anti-mCD122 mAb conditioned NOD/SCID mice, which recapitulated the characteristics of original disease.

Objective To analyze the effect ofmethylprednisolone stosstherapy on CD4+CD25+ regulatory T cell (Treg) and apoptosis factor CD95 expressions in the external peripheral blood of myasthenia gravis (MG) patients and explore the influencing factors of different clinical efficacy.Methods Thirty-one patients with MG,admitted to our hospital from January 2013 to September 2015,were included in this study;and 27 normal subjects were selected as control group.Methylprednisolone stosstherapy was given to the patient group.Expressions of Treg and CD95 in peripheral blood were detected by flow cytometry before and after treatment.Results Treg percentage of patients whose clinical absolute scale scores less or equal than 3 points and relative scale scores higher than 0.5 after methylprednisolonestosstherapy (13.39％+2.71％) was significantly higher than that ofhealthy controls (8.35％+1.87％,P＜0.05);Treg percentage of patients whose clinical absolute scale scores greater than 3 as well as relative scale scores less than 0.5 after methylprednisolone stosstherapy (8.17％+1.31％) was slightly lower than that of healthy controls (P＞0.05).CD95 percentage of patients whose clinical absolute scale scores less or equal than 3 points and relative scale scores higher than 0.5 after methylprednisolone stosstherapy (36.47％±5.32％) was not statistically different as compared with that of healthy controls (35.28％±5.58％,P＞0.05),CD95 percentage of patients whose clinical absolute scale scores greater than 3 as well as relative scale scores less than 0.5 after methylprednisolone stosstherapy (34.97％±5.12％) was not statistically different as compared with that of healthy controls (P＞0.05).Conclusion Treg ratio increases,CD95 change is not obvious in patients whose clinical curative effect is improved markedly after methylprednisolone stosstherapy.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia. However the poor prognosis and low morbidity restrict further analysis of the disease. Therefore there is an increasing demand to develop animal models for identifying novel therapeutic approaches. In this study, we inoculated the anti-mouse CD122 monoclonal antibody conditioned NOD/SCID mice with the leukemia cells from 9 T-ALL patients and 1 cell line via the tail vein. Four of the 9 patients and the cell line were successfully engrafted. Flow cytometry detected high percentage of human CD45(+) cells in recipient mice. Immunohistochemistry showed infiltration of human CD45(+) cells in different organs. Serial transplantation was also achieved. In vivo drug treatment showed that dexamethasone could extend survival, which was consistent with clinical observation. These results demonstrated that we successfully established 5 xenotransplantation models of T-ALL in anti-mCD122 mAb conditioned NOD/SCID mice, which recapitulated the characteristics of original disease.
Animals ; Disease Models, Animal ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Transplantation, Heterologous ; methods

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

Histone lysine specific demethylase 1 (LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound (IC = 3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound (IC = 49 nmol/L, and = 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3K4me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency of compound . Compound also showed strong antiproliferative activity against four leukemia cell lines (OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, significantly inhibited colony formation and caused remarkable morphological changes. Compound induced expression of CD86 and CD11b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation. The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazole-fused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1A inhibitors.