[Effects of BMAL2 on Aerobic Glycolysis and Cell Proliferation in Acute Myeloid Leukemia Cells].

OBJECTIVE: To explore the expression of basic helix-loop-helix ARNT like 2 (BMAL2) in acute myeloid leukemia (AML) patients and its correlation with prognosis, and analyze its effects on the aerobic glycolysis and proliferation of AML cells. METHODS: The expressions of BMAL2 in bone marrow mononuclear cells (BMMCs) of AML patients and normal control group were detected by RT-qPCR. The correlation of BMAL2 expression with prognosis of AML patients was analyzed using public database of National Center for Biotechnology Information (NCBI). The interfering in BMAL2 expression of HL-60 and Kasumi-1 cells was performed using lentiviral vector-mediated shRNA. Cell glucose metabolism and proliferation were detected by using glucose uptake experiment, lactate content test, CCK-8 assay and cell colony formation test. RESULTS: The expression level of BMAL2 mRNA in BMMCs of AML patients was significantly higher than normal control group (P < 0.01). The overall survival time of AML patients with high expression of BMAL2 was significantly shorter than those with low expression of BMAL2 (P < 0.05). Knockdown of BMAL2 significantly reduced glucose uptake and lactate production in AML cell line HL-60 and Kasumi-1 cells. The results of RT-PCR and Western blot showed that BMAL2 promoted aerobic glycolysis by enhancing the expression of HIF1A in AML cells, thereby promoting cell proliferation. CONCLUSION: BMAL2 is highly expressed in AML patients, and promotes aerobic glycolysis by enhancing the expression of HIF1A, thereby promoting cell proliferation.

Accuracy of Fasting Blood Glucose and Body Mass Index in Predicting Gestational Diabetes Mellitus in China.

BACKGROUND: Research suggests that lowering maternal morbidities associated with gestational diabetes mellitus (GDM) can be achieved with earlier risk group identification. AIMS: Therefore, the purpose of this study was to examine potential markers for identifying first-trimester pregnant women who are at high risk for developing GDM. METHODS: This was a retrospective cohort study. The pertinent maternal clinical data were retrieved prior to 13+6 weeks of gestation, and a binary logistic regression analysis was used to identify potential GDM predictors. The predictive accuracy was evaluated using the area below the receiver operating characteristics curves. RESULTS: In comparison to the control group, the GDM group had significantly higher mean values for age, body mass index (BMI), mean fasting blood glucose (FBG), and hemoglobin (p < 0.05). The Pearson's correlation coefficients indicated that the first-trimester FBG was significantly positively correlated with the second-trimester FBG. Higher FBG and BMI values were associated with an increased risk of developing GDM (odds ratio [OR] = 3.04, 95% confidence interval [CI] = 2.03-4.55 and OR = 1.18, 95% CI = 1.12-1.25). In terms of predicting GDM, the FBG parameter demonstrated the greatest area under the curve values (0.66), followed by the BMI parameter (0.69). For GDM prediction, the cut-off value for FBG was 4.32 mM, whereas that for BMI was 23.7 kg/m2. CONCLUSIONS: The first-trimester FBG and BMI could be utilized to predict gestational diabetes.

Investigating the Mechanism of Hyperglycemia-Induced Fetal Cardiac Hypertrophy.

Hyperglycemia in diabetic mothers enhances the risk of fetal cardiac hypertrophy during gestation. However, the mechanism of high-glucose-induced cardiac hypertrophy is not largely understood. In this study, we first demonstrated that the incidence rate of cardiac hypertrophy dramatically increased in fetuses of diabetic mothers using color ultrasound examination. In addition, human fetal cardiac hypertrophy was successfully mimicked in a streptozotocin (STZ)-induced diabetes mouse model, in which mouse cardiac hypertrophy was diagnosed using type-M ultrasound and a histological assay. PH3 immunofluorescent staining of mouse fetal hearts and in vitro-cultured H9c2 cells indicated that cell proliferation decreased in E18.5, E15.5 and E13.5 mice, and cell apoptosis in H9c2 cells increased in the presence of high glucose in a dose-dependent manner. Next, we found that the individual cardiomyocyte size increased in pre-gestational diabetes mellitus mice and in response to high glucose exposure. Meanwhile, the expression of ß-MHC and BMP-10 was up-regulated. Nkx2.5 immunofluorescent staining showed that the expression of Nkx2.5, a crucial cardiac transcription factor, was suppressed in the ventricular septum, left ventricular wall and right ventricular wall of E18.5, E15.5 and E13.5 mouse hearts. However, cardiac hypertrophy did not morphologically occur in E13.5 mouse hearts. In cultured H9c2 cells exposed to high glucose, Nkx2.5 expression decreased, as detected by both immunostaining and western blotting, and the expression of KCNE1 and Cx43 was also restricted. Taken together, alterations in cell size rather than cell proliferation or apoptosis are responsible for hyperglycemia-induced fetal cardiac hypertrophy. The aberrant expression of Nkx2.5 and its regulatory target genes in the presence of high glucose could be a principal component of pathogenesis in the development of fetal cardiac hypertrophy.

Exploring the Relationship Between Serum and Urinary Free Light Chain Levels During the Different Phases of Renal Damage in Multiple Myeloma Patients.

The objective was to explore the relationship between the levels of serum and urinary free light chains (FLCs) during the progression of renal damage in multiple myeloma (MM) patients. We examined 91 cases of MM patients, detected levels of serum FLCs (sFLCs), urinary FLCs (uFLCs), and serum creatinine at the same time, and then compared sFLC and uFLC levels during normal and abnormal serum creatinine phases. Among the 91 MM patients, 22 patients had abnormal serum creatinine levels (no uremia), and 69 patients had normal serum creatinine levels. The levels of sFLCs and uFLCs in patients with abnormal serum creatinine were beyond normal, namely both serum and urine positive (serum+ and urine+), and the average concentrations of κFLCs and λFLCs were 516.76 and 604.67 mg/L, respectively. Of the 69 patients with normal creatinine levels, there were 39 and 30 cases of κ-type and λ-type MM, respectively. Of the κ-type patients, 11 cases were serum positive and urine negative (serum+ and urine-) with an average concentration of 55.47 mg/L, and 28 cases were serum positive and urine positive (serum+ and urine+) with an average concentration of 513.09 mg/L. Of the λ-type patients, 16 cases were serum positive and urine negative (serum+ and urine-) with an average concentration of 78.44 mg/L, and 14 cases were serum positive and urine positive (serum+ and urine+) with an average concentration of 518.08 mg/L. The levels of uFLCs did not parallel those of sFLCs. In addition to sFLC levels, renal function affected uFLC concentrations. As MM progressed, the concentration of sFLCs increased in a step-by-step manner, and the uFLCs changed from negative to positive to negative again. Therefore, the whole progression included three phases: sserum+ and urine-, serum+ and urine+, and then serum+ and urine-.