The In Vivo Intervention and Relative Mechanism of Genistein on the Inflammation and Thrombophilia in Lymphoma-Bearing Mice / 中国实验血液学杂志

OBJECTIVE@#To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.@*METHODS@#Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX）drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.@*RESULTS@#After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05).@*CONCLUSION@#Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.

Effect of Coagulation and Platelet Activation on Tumor-Associated Hypercoagulable State in Lymphoma-Bearing Mice / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the coagulation abnormality and tumor-associated hypercoagulable state in lymphoma-bearing mice by measuring the changes in coagulation indices (D-D, vWF, TF) and platelet activation indices (P-selectin, GPIIbIIIa).</p><p><b>METHODS</b>The mouse model with lymphoma was established by the subcutaneous injection of 38B9 lymphoma cells into BALB/c mice, and the tumor formation was evaluated by using MRI and B ultrasonography. The D-D, vWF and TP levels of blood samples from inner canthal vein of tumor-bearing mice on 1 d, 14 d and 21 d were detected by using ELISA, the platelet activation indices (P-selectin, GPIIbIIIa) were detected by using flow cytometry.</p><p><b>RESULTS</b>The lymphoma-bearing mouse model was successfully established. The levels of D-D, vWF and TF as well as platelet activation indices P-selectin and GPIIbIIIa in the peripheraI blood were significantly higher than those of control group (P<0.05).</p><p><b>CONCLUSION</b>Lymphoma-bearing mice showed abnormalities of coagulation and platelet activation, which relates with the tumor hypercoagulable state in lymphoma-bearing mice.</p>

Regulation of UC-MSC on Immune Inflammatory Thrombophilia in MRL/lpr Mice / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the immune repair effect of umbilical cord mesenchymal stem cells (UC-MSC) on inflammatory disorders and thrombophilia state of MRL/lpr mice by detecting the expression change of peripheral blood CD4(+) CD25(+) T cells and the levels of plasma inflammatory cytokines TNF-α, IL-6 and thrombosis indicators TF, FIB.</p><p><b>METHODS</b>Twenty five MRL/lpr mice were divided into control (C) group, UC-MSC one time treatment (UT1) group and UC-MSC three time treatments (UT3) group. UC-MSC cell suspension was injecled via tail vein and these mice were feeded in SPF environment. The blood samples were taken from the mice every 2 weeks after 16(th) week. FCM was used to detect the expression of CD4(+) CD25(+) T cells in peripheral blood, ELISA assay was used to detect the levels of inflammatory cytokines TNF-α, IL-6 and thrombosis indicators TF, FIB.</p><p><b>RESULTS</b>The expression of peripheral blood CD4(+) CD25(+) T cells in treatment groups increased during 16(th) to 18(th) week, dropped and tended to be stable since 20(th) week, and lower than those in control group. The levels of plasma TNF-α and IL-6 in treatment group decreased since 16(th) week and significantly lower than those in control group (P < 0.05). The levels of plasma TF and FIB in treatment group decreased since 16(th) week. The level of plasma TF in treatment group was significantly lower than those in control group (P < 0.05) since 18(th) week.</p><p><b>CONCLUSION</b>UC-MSC can repair the immune inflammatory microenvironment disorders of MRL/lpr mice through its immunomodulatory effect. UC-MSC contribute to repair of immune inflammatory thrombophilia of MRL/lpr mice.</p>

Immunomodulatory effect of UC-MSC on function of immunocytes of rats with collagen type II induced arthritis / 中国实验血液学杂志

This study was purposed to observe the influence of umbilical cord mesenchymal stem cells (UC-MSC) on the peripheral blood CD4(+)CD25(+)regulatory T cells (Treg), Th17 cells and neutrophils in rats with collagen type II-induced arthritis(CIA), and to explore the regulating effect of UC-MSC transplantation on immunocyte subgroup. The rats wee divided into 3 groups: CIA group (model group), UC-MSC treated group and blank control group. The CIA rats were injected with UC-MSC via tail vein. The percentage of CD4(+)CD25(+) cells in peripheral blood and the expression of NCD11b on neutrophil surface in CIA rates was detected by flow cytometry (FCM), and the serum interleukin-17 (IL-17) was observed by enzyme-linked immunosorbent assay (ELISA). The results showed that the mean fluorescence intensity(MFI) of NCD11b and the level of IL-17 in the model group were significantly higher than those in the blank control group, and the ratio of CD4(+)CD25(+) cells were significantly lower (P < 0.05). The MIF of NCD11b and the level of IL-17 in the UC-MSC treated group were significantly lower than that in the model group (P < 0.05), while the proportion of CD4(+)CD25(+) Treg increased (P < 0.05). Since the fifth week, the above indicators in the UC-MSC group have almostly approached the control group. It is concluded that the UC-MSC can increase peripheral blood Treg proportion in CIA rat, inhibit the secretion of Th17 and the activity of neutrophils, reduce the immune inflammation reaction, decrease the release of proinflammatory factor, and induce immune reconstruction.

Evaluation of fluorescence in situ hybridization value in detection of chronic lymphocytic leukemia / 中国实验血液学杂志

The aim of this study was to investigate the clinical value of fluorescence in situ hybridization (FISH) in detecting the genomic aberration of chronic lymphocytic leukemia (CLL). FISH was used for 32 patients who were newly diagnosed as CLL. Five types of fluorescence probes with labeled DNA probes were included as sequence specific probes D13S25 for 13q14.3, P53 for 17p13.1, ATM for 11q22.3, RB1 for 13q14 and chromosomes 12. Meanwhile, FISH was used to detect IGH/CCND1 fusion gene in 10 CLL patients with untypical immunophenotypes. The results showed that out of 32 patients, 26 cases (81.3%) were abnormal including 14 cases of D13S25 deletion, 11 of RB1 deletion, 9 of trisomia 12, 6 cases of P53 deletion, and 1 of ATM deletion. 12 cases showed 1 kind of genomic aberration, including 7 cases of trisomia 12, 3 cases of D13S25 deletion, 1 of P53 deletion, 1 of ATM deletion. 11 eases displayed 2 kinds of abnormalities. Out of 11 cases, 7 were D13S25/RB1 deletion, 4 were of P53 deletion, and 3 cases had 3 kinds of abnormalities. Among 10 patients with CD5(+)CD23(-), two were positive with IGH/CCND1. It is concluded that the FISH can improve the detecting of chromosomal abnormalities in CLL, and every abnormality has its special feature. Detection of IGH/CCND1 seems important in diagnoses of CLL.

Effect of UC-MSCs on inflammation and thrombosis of the rats with collagen type II induced arthritis / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the immunoregulation effects of umbilical cord mesenchymal stem cells (UC-MSCs) on the rats with collagen II induced arthritis (CIA).</p><p><b>METHODS</b>The rats were first immunized by intradermal injection of chicken collagen type II emulsified with complete Freund's adjuvant (CFA) to monitor their swelling of foot, hair color and action state. After injected UC-MSC by caudal vein, the rats were scored with the arthritis index (AI) once a week. Then, the concentration of interleukin (IL-6), tumor necrosis factor-α (TNF-α) in serum and D-dimer (D-D), antithrombin-III (AT-III), thrombomodulin (TM) in plasma were detected by ELISA.</p><p><b>RESULTS</b>Obvious swellings of the feet were found in the experiment group compared with normal one. ELISA analysis showed that the concentrations of IL-6, TNF-α, D-D and TM in plasma of the experiment group as of (200.48 ± 15.04) ng/L, (450.25 ± 45.39) ng/L, (274.26 ± 67.93) ng/L and (9.18 ± 0.84) µg/L, respectively were higher than of(167.62 ± 0.97) ng/L, (371.44 ± 21.26) ng/L, (193.95 ± 8.22) ng/L and (6.30 ± 0.32) µg/L respectively in normal group (P < 0.05), but the concentration of AT-III \[(89.57 ± 6.40) ng/L\] was lower than normal group \[(112.82 ± 1.74) ng/L\] (P < 0.05). The levels of cytokines through the UC-MSCs treatment were significantly different from the model group (P < 0.05). After 9 weeks, these cytokines in the UC-MSCs group were mostly the same as the normal group.</p><p><b>CONCLUSION</b>The thrombophilia status of the CIA rats was caused by immune injury. The UC-MSCs reduced the production of inflammatory cytokines and regulated and repaired the balance of coagulation and anticoagulation system of the body to cure the immune-related thrombophilia.</p>