SLC22A8: An indicator for tumor immune microenvironment and prognosis of ccRCC from a comprehensive analysis of bioinformatics.

Clear cell renal cell carcinoma (ccRCC) is one of the most common renal malignancies worldwide. SLC22A8 plays a key role in renal excretion of organic anions. However, its role in ccRCC remains unclear; therefore, this study aimed to elucidate the relationship between SLC22A8 and ccRCC. The The Cancer Genome Atlas-kidney renal clear cell carcinoma cohort was included in this study. The Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between SLC22A8 expression and clinicopathological characteristics. Multifactorial analysis and Kaplan-Meier survival curves were adopted for correlation between SLC22A8 expression and clinicopathological parameters and overall survival. Utilizing the UALCAN database, the correlation of the expression levels of SLC22A8 DNA methylation in ccRCC was explored. Immunological characterization of SLC22A8 regarding the ccRCC tumor microenvironment was carried out by the single sample Gene Set Enrichment Analysis algorithm and the CIBERSORT algorithm. With the CellMiner database, the analysis of the association between SLC22A8 gene expression and drug sensitivity was further performed. Eventually, gene ontology and Kyoto Encyclopedia of Gene and Genome enrichment analyses were applied to identify the functional and signaling pathways involved in SLC22A8. SLC22A8 expression is associated with age, grade, stage, and tumor status. SLC22A8 protein expression levels, phosphorylated protein levels, and DNA methylation expression levels were lower in ccRCC tissues than in normal tissues, and low methylation levels predicted poor overall survival. Comprehensive analysis of tumor immune infiltration and the tumor microenvironment indicated a higher level of overall immunity in the SLC22A8 low expression group. Gene Enrichment Analysis results showed that low expression of SLC22A8 was associated with immune pathways, such as phagocytosis recognition and humoral immune response. SLC22A8 expression was significantly correlated with survival and immune infiltration in ccRCC and can be used as a prognostic biomarker for ccRCC.

The Predictive Efficacy of Serum Exosomal microRNA-122 and microRNA-148a for Hepatocellular Carcinoma Based on Smart Healthcare.

OBJECTIVE: Hepatocellular carcinoma (HCC) remains a devastating tumor globally. Serum exosomes are reliable biomarkers for tumors, including HCC. Hence, this study explored the efficacy and mechanism of serum exosomes in HCC. METHODS: microRNA (miR)-122 and miR-148a expressions in serum exosomes from HCC patients and healthy subjects and their predictive efficacy for HCC were detected. Correlation between serum exosomal miR-122/148a expressions with survival rate, clinical stage, lymph node metastasis, and tumor differentiation level and levels of HCC-related serum markers (CA199, FucAFP, ALD-A, and AFu) were detected. PAX2 staining intensity and expression in HCC were measured. PAX2 predictive efficacy for HCC and its correlation with clinical stage, lymph node metastasis, tumor differentiation level, and HCC-related serum marker levels were analyzed. The targeted binding relationship between miR-122 and miR-148a and PAX2 was predicted and verified. RESULTS: Serum exosomal miR-122 and miR-148a expressions were downregulated in HCC, showing potent predictive efficacy for HCC, which was negatively related to clinical stage and lymph node metastasis and positively related to tumor differentiation level, patient survival rate, and HCC-related serum marker levels. PAX2 showed increased staining intensity and expression in HCC, together with high predictive efficacy for HCC. PAX2 expression showed a positive correlation with clinical stage and lymph node metastasis and a negative correlation with tumor differentiation level and HCC-related serum marker levels. miR-122 and miR-148a conjointly targeted PAX2 in HCC. CONCLUSION: We demonstrated that serum exosomal miR-122 and miR-148a played a predictive role and were linked to prognosis in HCC via interactions with PAX2.

Knockdown of miR-106a suppresses migration and invasion and enhances radiosensitivity of hepatocellular carcinoma cells by upregulating FBXW7.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. microRNAs (miRNAs) have been reported to play essential roles in HCC progression and radiosensitivity. However, the effect of miR-106a on HCC progression and radiosensitivity as well as its mechanism remain largely unknown. The expressions of miR-106a and F-box and WD repeat domain containing 7 (FBXW7) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot, respectively. Cell migration and invasion were analyzed by trans-well assay. The radiosensitivity was investigated by colony formation and western blot. The interaction between miR-106a and FBXW7 was explored by luciferase activity and RNA immunoprecipitation (RIP) analyses. Then miR-106a expression was elevated in HCC tissues and cells and associated with tumor stage as well as overall survival. Knockdown of miR-106a impeded cell migration and invasion but contributed to irradiation-induced inhibition of survival and increase of phosphorylation of histone in Serine 139 (γ-H2AX) protein in HCC cells. Moreover, FBXW7 was indicated as a target of miR-106a and negatively correlated with miR-106a. Besides, interference of FBXW7 reversed the regulatory effect of miR-106a abrogation on migration, invasion and radiosensitivity in HCC cells. The results showed down-regulation of miR-106a suppressed migration and invasion and increased radiosensitivity of HCC cells by targeting FBXW7, providing a novel avenue for HCC treatment.

[Prognostic significance of morbidly hematopoietic characteristics in 69 patients with myelodysplastic syndrome].

OBJECTIVE: This study was to investigate the influence of morbidly hematopoietic characteristics on the prognosis of patients with myelodysplastic syndrome (MDS). METHODS: A total of 69 cases of MDS were analyzed retrospectively on ralatienship between sex, age, MDS types, WBC count, hemoglobin (Hb) level, platelet (Plt) count at diagnosis, morbidly cytologic features of bone marrow and survival time of MDS patients. RESULTS: The median survival time of 69 cases of MDS was 29.90 months. The patients of different sexes and Plt level at diagnosis did not display statistically significant difference in median survival time (P > 0.05); the patients with different ages, WBC count and Hb level showed statistically significant difference in median survival time (P < 0.05); the median survival time of patients with different MDS types was significant different (P < 0.01); the MDS patients with myeloid lineage containing nuclear plasma development imbalance, micronuclei, abnormal mitotic figures, with erythroid lineage containing megaloblastic degeneration, cell size disparity, nuclcar budding and muclear fragmentation, and with megakaryocyte lineage containing micromegaryocytes, excessive muclear leaves, displayed significant difference in median survival time (P < 0.05). The MDS patients with ALIP positive, fibrosis in bone marrow blopsy showed significant difference in median survival time. CONCLUSION: The age, MDS types, Hb level and WBC count at diagnosis are indicators influencing the prognosis. The unbalanced development of muclear plasma, micronuclei, abnormal mitotic figures in myeloid morbid hematopoiesis, the megaloblastic degeneration, cell size disperity, muclear budding, nuclear fragmentation in erythroid morbid hematopoiesis, the micro-megakaryocytes, excessive nuclear leaves in megakaryocytic morbid hematopoiesis, and existance of ALIP posstive and fibrosis in bone marrow biopsy indicate important values for evaluation of MDS prognosis.

Tetramethylpyrazine potentiates arsenic trioxide activity against HL-60 cell lines

The objective of this study was to evaluate the effects of tetramethylpyrazine (TMP) in combination with arsenic trioxide (As2O3) on the proliferation and differentiation of HL-60 cells. The HL-60 cells were treated with 300 µg/mL TMP, 0.5 µM As2O3, and 300 µg/mL TMP combined with 0.5 µM As2O3, respectively. The proliferative inhibition rates were determined with MTT. Differentiation was detected by the nitroblue tetrazolium (NBT) reduction test, Wright’s staining and the distribution of CD11b and CD14. Flow cytometry was used to analyze cell cycle distribution. RT-PCR and Western blot assays were employed to detect the expressions of c-myc, p27, CDK2, and cyclin E1. Combination treatment had synergistic effects on the proliferative inhibition rates. The rates were increased gradually after the combination treatment, much higher than those treated with the corresponding concentration of As2O3 alone. The cells exhibited characteristics of mature granulocytes and a higher NBT-reducing ability, being a 2.6-fold increase in the rate of NBT-positive ratio of HL-60 cells within the As2O3 treatment versus almost a 13-fold increase in the TMP + As2O3 group. Cells treated with both TMP and As2O3 expressed far more CD11b antigens, almost 2-fold compared with the control group. Small doses of TMP potentiate As2O3-induced differentiation of HL-60 cells, possibly by regulating the expression and activity of G0/G1 phase-arresting molecules. Combination treatment of TMP with As2O3 has significant synergistic effects on the proliferative inhibition of HL-60 cells.

Tetramethylpyrazine potentiates arsenic trioxide activity against HL-60 cell lines.

The objective of this study was to evaluate the effects of tetramethylpyrazine (TMP) in combination with arsenic trioxide (As2O3) on the proliferation and differentiation of HL-60 cells. The HL-60 cells were treated with 300 µg/mL TMP, 0.5 µM As2O3, and 300 µg/mL TMP combined with 0.5 µM As2O3, respectively. The proliferative inhibition rates were determined with MTT. Differentiation was detected by the nitroblue tetrazolium (NBT) reduction test, Wright's staining and the distribution of CD11b and CD14. Flow cytometry was used to analyze cell cycle distribution. RT-PCR and Western blot assays were employed to detect the expressions of c-myc, p27, CDK2, and cyclin E1. Combination treatment had synergistic effects on the proliferative inhibition rates. The rates were increased gradually after the combination treatment, much higher than those treated with the corresponding concentration of As2O3 alone. The cells exhibited characteristics of mature granulocytes and a higher NBT-reducing ability, being a 2.6-fold increase in the rate of NBT-positive ratio of HL-60 cells within the As2O3 treatment versus almost a 13-fold increase in the TMP + As2O3 group. Cells treated with both TMP and As2O3 expressed far more CD11b antigens, almost 2-fold compared with the control group. Small doses of TMP potentiate As2O3-induced differentiation of HL-60 cells, possibly by regulating the expression and activity of G0/G1 phase-arresting molecules. Combination treatment of TMP with As2O3 has significant synergistic effects on the proliferative inhibition of HL-60 cells.

[Molecular mechanism of tetramethylpyrazine to induce human promyelocytic HL-60 leukemia cells differentiation].

OBJECTIVE: To study the molecular mechanism of tetramethylpyrazine to induce human promyelocytic HL-60 leukemia cells differentiation. METHOD: The cell proliferation was determined by MTT. The differentiation of the cells was detected by NBT reduction test. Cellular morphology was observed by Wright's staining. Cell cycle distribution and the distribution of CD11b, CD14 were detected by flow cytometry. Then RT-PCR and Western blot assay were employed to detect the expressions of c-myc, p27, CDK2 and cyclinE1 in HL-60 cells after exposure to TMP. RESULT: TMP inhibited the proliferation in a dose and time dependent manner. TMP at the concentration of 200 mg x L(-1) to 300 mg x L(-1) induced unterminal differentiation of HL-60 cell and synergistically blocked the cell cycle progression of HL-60 cells in G0/G1 phase. The expression of c-myc was down-regulated as well as the protein expression of cyclin E and CDK2, while the mRNA and protein expression of P27 were remarkably up-regulated. CONCLUSION: Small doses of TMP induces differentiation of HL-60 cells throughout the cell cyde, as detected by a slower rate of accumulation in G0/G1, possibly by regulating the expression and activity of G1/S phase-related molecules.