MicroRNA-126 inhibits colon cancer cell proliferation and invasion by targeting the chemokine (C-X-C motif) receptor 4 and Ras homolog gene family, member A, signaling pathway.

MicroRNA-126 (miR-126) suppresses the migration, proliferation and invasion of colon cancer cells. However, the underlying mechanisms of miR-126 in colon cancer have not been fully elucidated. In this study, in vivo experiments revealed that miR-126 inhibits colon cancer growth and metastasis. Furthermore, miR-126 was down-regulated in human colon cancer tissue, and its expression was inversely correlated with TNM stage and metastasis of patients. Low level of miR-126 identified patients with poor prognosis. And we found that miR-126 expression was negatively correlated with the expression levels of chemokine (C-X-C motif) receptor 4 (CXCR4) and components of signaling pathway of Ras homolog gene family, member A (RhoA) in vitro and in vivo. Moreover, we verified that miR-126 negatively regulated CXCR4 and RhoA signaling in vitro. In addition, either in miR-126-overexpressing or in miR- 126-silenced colon cancer cells, the restoration of CXCR4 could significantly reverse the proliferation and invasion, as well as abolish the effects of miR-126 on RhoA signaling pathway. Collectively, these results demonstrated that miR-126 acts as a tumor suppressor by inactivating RhoA signaling via CXCR4 in colon cancer. And miR-126 may serve as a prognostic marker for monitoring and treating colon cancer.

Grade-specific expression profiles of miRNAs/mRNAs and docking study in human grade I-III astrocytomas.

Although several miRNAs have been identified to be involved in glioblastoma tumorigenesis, little is known about the global expression profiles of miRNAs and their functional targets in astrocytomas at earlier stages of malignancy. In this study the global expression of miRNAs and mRNAs in normal brain tissue samples and grade I-III astrocytomas were analyzed parallelly using microarrays, and the grade-specific expression profiles of them were obtained by unsupervised hierarchical clustering. It was also confirmed that miR-107, miR-124, miR-138, and miR-149 were downregulated significantly in grade I-IV astrocytomas, and overexpression of miR-124 and miR-149 inhibited glioblastoma cell proliferation and migration. Furthermore, grade-specific changes were discovered in the central biological processes, regulatory networks, and signaling pathways associated with dysregulated genes, and a regulatory network of putative functional miRNA-mRNA pairs was defined. In conclusion, our results may contribute to a better understanding of the molecular mechanisms involved in astrocytoma tumorigenesis and malignant progression.

Impact of experimental and demographic variables in serum peptide profiling based on magnetic bead and MALDI-TOF mass spectrometry.

BACKGROUND: Serum peptidome profile is a promising tool to identify physiologic or pathologic conditions. Stable serum peptidome profiles with high quality are essential for serum peptidome research. The aim of this study is to examine the impact of experimental and demographic variables in serum peptide profiling. METHODS: Magnetic bead combined with MALDI-TOF mass spectrometry was performed to evaluate the efficacy of various variables including the treatment of blood, the pretreatment of serum (magnetic beads and ultrafiltrate centrifugal filters), the mass spectrometry and the data handling. The influence of age and gender on serum peptidome was also analyzed in 123 healthy volunteers. RESULTS: The results showed that the sampling processing procedures were crucial for the serum peptidome profiles. There were obvious differences on the serum peptidome profiles between the age groups younger and older than 30. There was no difference between gender groups. CONCLUSIONS: A number of optimized and standardized variables should be defined in serum peptidome research based on magnetic beads and MALDI-TOF mass spectrometry. An extremely strict standard procedure and considerate arrangement should be applied.

Stage-associated dynamic activity profile of transcription factors in nasopharyngeal carcinoma progression based on protein/DNA array analysis.

Transcription factors (TFs) are crucial modulators of gene regulation during the development and progression of tumors. We previously reported the activation of TFs in nasopharyngeal carcinoma (NPC) cell lines. In this study, we explored the activity profiles of TFs in Protein/DNA array data of a 12-tissue independent set and a 13-tissue pooled set of NPC that included different clinical stages. TFs associated with tumor progression were revealed using a generalized linear model-based regression analysis. Immunohistochemical analysis of clinical NPC samples was used to validate the results of array analysis. We identified 26 TFs that showed increased activities. Of these 26 TFs, 16 were correlated with clinical stages. Activity changes of AP2 and ATF/CREB were confirmed by electrophoretic mobility shift assay (EMSA), and increased expression of AP2α, ß, γ, ATF2, and ATF1 in nuclei of tumor cells was associated with clinical stages. In addition, the expressions of AP2α, ATF2, and ATF1 were correlated with those of their target genes (epithelia growth factor receptor (EGFR) and matrix metalloproteinase 2 (MMP-2), respectively). This study provides data and valuable clues that can be used to further investigate the laws of gene transcription regulation in NPC and to identify suitable targets for the development of TF-targeted antitumor agents.

Tacrolimus combined with corticosteroids in treatment of nephrotic idiopathic membranous nephropathy: a multicenter randomized controlled trial.

BACKGROUND: Idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults, is usually treated with corticosteroids in combination with cyclophosphamide or cyclosporine. A recent placebo-controlled study suggested that tacrolimus monotherapy was effective in IMN. However, the effectiveness of tacrolimus versus classic regimen and its potential nephrotoxicity remain inconclusive. This study evaluated the efficacy and safety of tacrolimus plus prednisone in patients with nephrotic IMN. METHODS: Seventy-three patients with nephrotic IMN were recruited in this multicenter randomized controlled trial, 39 receiving tacrolimus and prednisone, while 34 receiving cyclophosphamide and prednisone. Tacrolimus was given at 0.1 mg/kg/d initially and adjusted to a blood trough level at 5 to 10 ng/mL for 6 months and then reduced to 2 to 5 ng/mL in the subsequent 3 months. RESULTS: Intention-to-treat analysis suggested that the remission rate at the end of the sixth month was significantly higher in tacrolimus group than that in cyclophosphamide group (85% versus 65%, P < 0.05). The decrease of proteinuria was significantly greater in tacrolimus group. At the end of the 12th month, the remission rates were comparable between these 2 groups. Patients treated with tacrolimus were more likely to develop glucose intolerance (or diabetes mellitus), infection, and hypertension. No obvious nephrotoxicity of calcineurin inhibitor was found in repeat renal biopsy. CONCLUSIONS: Tacrolimus plus corticosteroids is an alternative therapeutic regimen for nephrotic IMN. The short-term efficacy might be better than cyclophosphamide plus prednisone.

[Clinical observation on treatment of chronic allograft nephropathy with colquhounia root tablet combined with immunosuppressive protocol].

OBJECTIVE: To observe the effects of Colquhounia root tablet (CRT) combined with immunosuppressive protocal in treating patients with chronic allograft nephropathy (CAN). METHODS: Thirty-three patients of CAN, with urinary protein > or = 1.0 g/24 h and serum creatinine (SCr) > or =150 (micromol/L), were assigned to two groups, the 15 in the treated group treated with CRT combining modified immunosuppressive protocol (IIP) therapy and the 18 in the control group treated with IIP alone, all for 6 months. The clinical efficiency, 24 h urinary protein and clearance of creatinine (CCr) were observed. RESULTS: The effective rate in the treated group [60% (9/15 cases)] was significantly higher than that in the control group [22.0% (4/18 cases), P < 0.05], and the lowering of 24 h urinary protein in the former was more significant than in the latter at the end of the 3rd and the 6th month of treatment (P < 0.05). At the end of 12-month follow-up, SCr and CCr level were stable in the treated group, while in the control group, SCr level increased and CCr level decreased significantly (P < 0.05), comparisons of the two indexes between the two groups at the end of the therapeutic course and follow-up study all showed significant differences (P < 0.05). Serum creatinine doubling to baseline were seen in 2 patients of the treated group and 7 of the control group. One patient in the treated group and 4 in the control group entered the end stage of renal disease. CONCLUSION: Therapy with CRT combined IIP seems to be more effective in reducing urinary protein excretion in patients with CAN than that with IIP alone, and a more favorable renal function preserving effect of the former is shown by a short-term follow-up.

Effect of detoxification, removing stasis and nourishing yin method on corticosteroid-induced hyperlipidemia in patients with systemic lupus erythematosus.

OBJECTIVE: To observe the effect of TCM therapy for detoxification, removing stasis, and nourishing yin on corticosteroid-induced hyperlipemia in patients with systemic lupus erythematosus (SLE), and to investigate its mechanism. METHODS: One hundred and seventy patients with SLE were randomly assigned to the integrative medicine group (IM group) and the Western medicine group (WM group), 85 in each group. Also, 30 healthy subjects selected from blood donors were enrolled in the normal control (NC) group. All patients were treated mainly with prednisone, while those in the IM group were given TCM therapy additionally, and the therapeutic course for both groups was 6 successive months. The changes of serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and apolipoprotein A (ApoA) were determined and observed. A 2-year follow-up study was carried out in 16 patients of the WM group and 25 of the IM group. RESULTS: Before treatment, no significant difference had been found among the three groups in the serum levels of lipids and lipoproteins. After the 6-month treatment, as compared with the WM group, the IM group showed lower levels of TC, TG, LDL-C, and VLDL-C (P<0.05 or P<0.01) and higher levels of HDL-C and ApoA (P<0.05). A similar effect was also shown by the follow-up study in the IM group (P<0.05 or P<0.01). CONCLUSION: TCM therapy for detoxification, removing stasis, and nourishing yin can effectively regulate the levels of serum lipids and lipoproteins in preventing and treating SLE patients with corticosteroid-induced hyperlipemia.

[Nested case-control study on the influence factors of perinatal stage transmission of hepatitis B virus].

OBJECTIVE: To determine the influence factors of perinatal stage transmission of hepatitis B virus (HBV) and to provide scientific evidence for the prevention of perinatal stag transmission of HBV. METHODS: A 1:1 matched nested case-control study was conducted, and 141 pair of pregnant women with HBsAg-positive and their newborns were enrolled. A questionnaire was performed and blood-related indicators were detected. The data were dealt with single factor analysis and conditional logistic regression analysis using SPSS 13.0 and SAS 8.1. RESULTS: Single factor paired Chi-square test showed that education, first class family history, disfunction of liver, serum glutamic-pyruvic transaminase, systematic treatment, intrahepatic cholestasis of pregnancy (ICP), fetal distress, and vaccinating hepatitis B immune globulin (HBIG) were the risk factors of perinatal stage transmission of HBV. Conditional logistic regression analysis indicated that first class family history, vaccinating HBIG, systematic treatment, and ICP were the risk factors of perinatal stage transmission of HBV. CONCLUSION: For women with HB-sAg-positive, active treatment, the standard vaccination of HBIG, and preventing and controlling the incidence of ICP may reduce the incidence of perinatal stage transmission of HBV.