[MicroRNA-221/222 participates in the pathogenesis of intrahepatic cholestasis of pregnancy via promoting the apoptosis of human placental trophoblast HTR-8 cells].

Objective: MicroRNA-221/222 is involved in the pathogenesis of intrahepatic cholestasis of pregnancy (ICP) to promote the apoptosis of placental bile acids through human trophoblastic cells. This study investigates the effects of miR-221/222 on proliferation, apoptosis and apoptosis-related proteins of human trophoblast HTR-8/SVneo (HTR-8 cells) to understand its role in promoting trophoblastic apoptosis. Methods: The experiment was divided into transfection group and negative control group. Transient transfection method was used in both groups. The transfection efficiency was detected by RT-QPCR after 48 h transfection. CCK-8 was used to detect the proliferation of HTR-8 cells and the apoptosis of HTR-8 cells were analyzed by flow cytometry. Western blot was used to detect the expression of B-cell Lymphoma 2 (Bcl-2) in HTR-8 cells. Data were compared with t-test. Results: The expression of miR-221/222 transfected group (25.43±0.80, 22.70±0.95) was increased significantly in the HTR-8 cells than that to negative control group (1.14±0.14, 1.58±0.14), and P value was < 0.01, the difference was statistically significant. The expression of Bcl-2 protein in mir-221/222 transfection group was (0.56 ± 0.03, 0.53 ± 0.03), and the protein expression was decreased compared with negative control group (0.72 ± 0.003, 0.76 ± 0.04). P value was < 0.05, the difference was statistically significant, and compared with the mir-221/222 negative control group (8.827 ± 0.48, 11.80 ± 0.45), cell apoptosis of mir-221/222 transfection group (42.53 ± 4.47, 24.09 ± 2.53) increased significantly, P value was < 0.01, and the difference was statistically significant. Proliferation rate in mir-221/222 transfection group was (0.82 ± 0.02, 0.74±0.01), and proliferation was inhibited, when compared with control group (1.15 ± 0.08, 1.06 ± 0.08), P value was < 0.05, and the difference was statistically significant. Conclusion: miR-221/222 may promote the apoptosis of human trophoblastic cells by down regulating the expression of apoptosis inhibitory protein bcl-2, leading to placental dysfunction and impairing the normal bile acid transport function of placenta. This mechanism may be involved in the occurrence and development of ICP.

Human herpesvirus 6 in hematologic diseases in China.

BACKGROUND AND OBJECTIVE: The prevalence and pathogenic role of human herpesvirus 6 (HHV-6) in various benign and malignant hematologic diseases remain largely unknown. The aim of this study was to search for a possible involvement of HHV-6 in the pathogenesis of hematologic diseases. DESIGN AND METHODS: The presence of HHV-6 DNA sequences was examined by polymerase chain reaction (PCR) in bone marrow mononuclear cells from 241 patients with benign and malignant hematologic diseases in China. Platelet-associated immunoglobulin (PAIg) of 66 idiopathic thrombocytopenic purpura (ITP) patients was measured by competitive enzyme-linked immunosorbent assay. The presence of HHV-6 DNA in sera from 31 ITP patients was examined by PCR. Paired serum samples from 19 ITP patients were analyzed for anti-HHV-6 IgG titers using an indirect immunofluorescence assay. RESULTS: HHV-6 DNA was detected in 41% and 37.5% of ITP and acute leukemia patients respectively, but in only 6.7% of patients with iron deficiency anemia. HHV-6 positivity for ITP patients with excessive PAIgG was significantly higher than in patients with a normal level of PAIgG. HHV-6 DNA was not detected in any of the serum samples from ITP patients. None of the 19 cases of ITP showed a significant increase in anti-HHV-6 antibody titers during the convalescent phase compared with the onset phase. INTERPRETATION AND CONCLUSIONS: Our results indicate that HHV-6 infection might be associated with excessive PAIgG in some cases of ITP, and that the virus persists in a latent state. The pathogenic role of HHV-6 in ITP needs to be confirmed by further investigations.

[Relationship between the familial nonrandom chromosome loss (NCL) and leukomogenesis].

By using R-banding karyotypic analysis technique, the bone marrow (BM) cells were performed in 223 hematopoietic malignacies and 105 diopathic throbocytopenic purpura (ITP), which served as control. The following results were obtained: (1) Nonrandom chromosome loss (NCL), such as, -11, -14, -21, etc, which were found in the affected members of leukemia families, were found in about 30% sporadic ANLL, MDS and about 50% ALL, espedislly in 100% (5/5) CLL, but not found in ITP (P < 0.001). These results indicated that the familial nonrandom chromosome loss were associated with leukomogenesis. (2) Because most of BM cells are hypodiploed and have the same kinds of NCL in each cases of CLL, which can develop into ALL, ANLL and also cancers, ALL BM hypo- and hyper-diploid and/or polyploid cells might be origin of hypodiploid cells. (3) 28% (6/21) of pediatric patients with AL, MDS, or FA (Fanconi Anemia) have one parent, who have up to 30% BM hypodiploid cells and similar kinds of NCL and also have the rearrangement of C-erbB and abnormal proliferation of BM. The NCL were found in the three consecutive generations of a family with 5 ALL among 10 members of third generation. It indicated that the familial NCL might be inherited and be coded by a unknown gene alteration, which might be related to leukomo and carcinogenesis, because there are genes or their candidates for leukemia in the chromosomes 11, 14 and 21. (4) Based on the works of my colleages and I, the model of leukomo and carcinogenesis was proposed and the relationship between chromosome monosomy, deletion, translocations and leukomogenesis were showed elswhere. The significance of monosomy 11, 14 and 21 etc. were discussed briefly.