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Hypoxia is one of the significant characteristics of the microenvironment of malignant tumors in the blood system. Hypoxic microenvironment can promote the metastasis and infiltration of tumor cells, which is one of the key factors leading to treatment tolerance, and also an important factor for resistance against tumor immune response. In acute myeloid leukemia (AML), the cellular oxygen sensing pathway is an important signaling transduction pathway that participates in the cell's response to hypoxic environments and can regulate biological processes such as metabolism, growth, and survival. Starting from how hypoxia affects the oxygen sensing pathway of leukemia cells, and targeting the cell adaptation mechanism induced by hypoxia, exploring new directions for targeted treatment of hematological malignancies in hypoxic environments can provide new ideas and theoretical support for the treatment of AML.
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As an effective treatment for cancer, chemotherapy not only removes tumor cells, but also produces obvious killing effects on proliferating cells, especially hematopoietic cells, resulting in bone marrow suppression after chemotherapy, and affecting the effects of chemotherapy drug treatment and treatment cycle. Therefore, starting from the aspects of hematopoietic microenvironment damage and hematopoietic stem cell aging, to explore the mechanism of myelosuppression after chemotherapy, which provides new ideas and theoretical support for the intervention and management of bone marrow suppression after cancer chemotherapy.
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Objective:To study the expression of miRNA-7 in B lymphocytes of primary Sj?gren's syndrome (pSS) and its relationship with phosphatase andtensin homolog deleted (PETN) and disease activity.Methods:Twenty newly diagnosed outpatient and inpatient pSS patients were used as case group collected from January 2017 to December 2019 of Qinghai Provincial People's Hospital. Twentyhealthy persons were used as the control group. Disease-related indicators of the case group were collected. Quantitative polymerase chain reaction (RT-qPCR)was used to detect miRNA-7 and PETN mRNA expression in B lymphocytes of the two groups and the consistency between miRNA-7 expression in the plasma and B lymphocytes of the case group was analyzed. Western Blotting method was used to detect the PETN protein in B lymphocytes of the two groups. Correlation analysis was used to analyze the relationship between miRNA-7 expression in B lymphocytes and disease activity in the case group. Linear regression analysis was performed between miRNA-7 and PETN mRNA.Results:The expression of miRNA-7 (0.53±0.17) in the B cells increased and the expression of PTEN mRNA (0.88± 0.24) and protein (0.51±0.12) in the case group were reduced compared with that of miRNA-7(0.39±0.11), PTEN mRNA(2.32±0.30) and protein(1.03±0.21) of the control group. The above differences were statistically significant ( t=2.990, P<0.05; t=16.98, P<0.05; t=8.41, P<0.05). Linear regression showedthat PTEN miRNAwas negatively correlated with miRNA-7 ( b=-0.78, P<0.01), the expression of miRNA-7 in the case group was positively related with EULAR Sj?gren′s syndrome Disease Activity Index (ESSDAI), IgG, IgA, anti-SSB and was negatively correlated with C4 and WBC. Conclusion:There is a certain relationship between miRNA-7 and disease activity. MiRNA-7 may participate in the pathogenesis of pSS byregulating PETN in B cells of pSS. MiRNA-7 has certain clinical value for disease activity evaluation.
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Objective To investigate the expression of miR-372 in the plasma of patients with acute my-eloid leukemia(AML)and the possible mechanism to participate in the development of AML. Methods Real-time quantitative PCR was used to detect the level of miR-372 in plasma. Bioinformatics software predicted the pos-sible target genes of miR-372 and dual luciferase reporter assay was performed to validate the prediction. In HL-60 cells,miR-372 was knocked down,and the effects on cell migration and cloning were detected by scratch test and clone formation. Results The level of miR-372 was significantly up-regulated in the plasma of AML patients. ROC analysis showed that miR-372 could distinguish between AML patients and healthy controls. Dual luciferase report-er assay showed that miR-372 could inhibit the activity of PTEN-3'UTR. Inhibition of miR-372 in HL-60 cells can significantly reduce the cell migration rate and clone formation ability. Conclusion In summary,for the first time,we showed novel data that the level of miR-372 was increased in the plasma of AML patients. By targeting the tumor suppressor gene PTEN,miR-372 may become a potential noninvasive biomarker for the screening and di-agnosis of AML.