Umbilical Cord Blood Betaine in Infants Born Small for Gestational Age.

Background: Birth weight is of importance due to its relation to fetal health, and it's also a predictor of the subsequent development of the child. Objective: This study aims to assess whether betaine is associated with poor fetal growth. Design: A case-control study was used in this study. Setting: The study took place at the Chongqing Maternal and Child Health Hospital, in Chong Qing, China. Participants: A total of 141mother-infant pairs were recruited from the Department of Obstetrics of our hospital between June 2021 and December 2021. According to gestational age and birth weight, themother-infant pairs were divided into small-for-gestational-age and appropriate-for-gestational-age groups. Primary Outcome Measures: Cord plasma concentrations of betaine were measured by high-performance liquid chromatography tandem mass spectrometry. Plasma levels of triglycerides, low-density lipoprotein, high-density lipoprotein and total cholesterol were determined using commercially available assays on an automatic biochemical analyzer (BS-240 VET, Mindray Medical, Shenzhen, China) using reagent from Mindray Medical company. Results: Cord plasma betaine concentrations were higher in small-for-gestational-age relative to appropriate-for-gestational-age newborns, and were not correlated to lipid levels. Adjusting for maternal and neonatal characteristics, birth weight and birth length were negatively correlated with the levels of betaine. Higher betaine concentrations were associated with increased risks of small-for-gestational-age. Conclusions: Elevated cord blood betaine concentration was independently associated with a higher risk of small-for-gestational-age infants, suggesting that betaine dysregulation may be a risk factor for impaired fetal growth.

The association between umbilical cord blood fat-soluble vitamin concentrations and infant birth weight.

Background: Fat-soluble vitamins, including vitamins A, D and E, play an important role in the regulation of glucose and lipid metabolism, and may affect infant birth weight. Evidence on the association of birthweight with fat-soluble vitamins is controversial. Therefore, this study aims is to determine the associations of birthweight with vitamin A, D, and E concentrations in cord blood. Methods: A total of 199 mother-infant pairs were enrolled in the study. According to gestational age and birth weight, the mother-infant pairs were divided into small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). The Vitamin A, D, and E concentrations in serum were measured by high-performance liquid chromatography tandem-mass spectrometry. Results: The concentrations of vitamin A in the SGA group were significantly lower than those in the AGA and LGA groups. The concentrations of vitamin E in the SGA group were significantly higher than those in the AGA and LGA groups. However, no significant differences were observed in vitamin D among the three groups. Being male (ß = 0.317, p < 0.001) and birth weight (ß = 0.229, p = 0.014) were positively correlated with the levels of vitamin A. Birth weight (ß = -0.213, p= 0.026) was correlated with lower levels of vitamin E. No correlation was found between influencing Factors and the levels of vitamin D (p> 0.05). After adjusting for gestational age, sex, mother's age, delivery mode, pre-pregnancy BMI, and weight gain during pregnancy, the levels of cord blood vitamin A were positively correlated with birth weight (p=0.012). Conclusion: The infant's birth weight is associated with the levels of cord blood vitamins A and E. The dysregulation of vitamins A and E in infants may be a risk factor for fetal growth and future metabolic diseases.

The expression and function of E3 ligase SIAH2 in acute T lymphoblastic leukemia.

INTRODUCTION: The seven in absentia homolog 2 (SIAH2) protein plays a significant role in human cancer by regulating hypoxia-inducible factor-a (HIF-1α); however, its role in T-cell acute lymphoblastic leukemia (T-ALL) is less clear. METHODS: Immunofluorescence evaluation of SIAH2 protein expression and location were conducted in Jurkat cell (a T-ALL cell line) as well as in bone marrow mononuclear cells (BMMNCs) from T-ALL and idiopathic thrombocytopenic purpura (ITP) patients. The expression of SIAH2 mRNA was also examined by quantitative real-time PCR (qRT-PCR) in these cells. Lentivirus-packed shRNA targeting on SIAH2 (Lv-shSIAH2) was used to knock down SIAH2 expression in Jurkat cells. Cell proliferation, apoptosis, invasion and protein levels were then determined by CCK-8 assay, annexin V-PI assay, transwell and Western blotting, respectively. RESULTS: The mRNA expression of SIAH2 in BMMNCs from primary T-ALL patients was significantly higher than cells from ITP patients (P=0.0312); There were significant positive associations between SIAH2 expression and the extramedullary infiltration (EMI) (P=0.0003), especially with the mediastinal lymph node metastasis (P=0.0168) and the pleural effusion (P=0.014). However, SIAH2 expression in T-ALL BMMNCs was not correlated with age, gender, white cell count or the clinical risk classification. SIAH2 knockdown by shRNA led to increased apoptosis and decreased proliferation, migration and invasion of Jurkat cells. Moreover, Prolyl Hydroxylase (PHD), P27 and Caspase3 were upregulated and HIF-1α, VEGF, VEGF Receptor 2, MMP-13, CyclinE1, C-myc and BCL2 were downregulated in SIAH2 knockdown Jurkat cells. CONCLUSIONS: Our results suggest that SIAH2 regulates multi processes in T-ALL and may be an attractive therapeutic target.

[Study on effect of tetramethylpyrazine on proliferation and apoptosis of leukemic U937 cells and its mechanism].

OBJECTIVE: To study the proliferation and apoptosis of tetramethylpyrazine (TMP) on leukemic U937 cells and its possible mechanism. METHOD: The inhibitory effect of TMP on the proliferation of U937 cells was detected by CCK-8 assay. The cell apoptosis and cycle distribution were examined by the flow cytometry. The mRNA expressions of bcl-2 and P27 were determined by the Real-time PCR. Western blot was carried out to detect bcl-2, caspase-3, cyclin E1, CDK2 and P27 expressions. RESULT: TMP inhibited the proliferation of U937 cells in a dose-and-time dependent manner, with IC50 value of 160 mg x L(-1) at 48 h. In addition, TMP could induce the apoptosis of U937 cells and block the cell cycle in G0/G1 phase. According to the results of Real-time PCR and Western blot, TMP could down-regulate the expression of apoptosis-related molecule bcl-2, cycle-related protein cyclin E1 and CDK2 and up-regulate caspase-3 and P27. CONCLUSION: TMP shows the effects in inhibiting the proliferation of leukemic U937 cells and inducing the apoptosis. Its mechanism may be related to the impacts on the cell cycle distribution, down-regulation of the bcl-2 expression, which finally activates caspase-3, starts the apoptosis path and causes the cell apoptosis.

Acute Lymphoblastic Leukemia Cells Inhibit the Differentiation of Bone Mesenchymal Stem Cells into Osteoblasts In Vitro by Activating Notch Signaling.

The disruption of normal hematopoiesis has been observed in leukemia, but the mechanism is unclear. Osteoblasts originate from bone mesenchymal stem cells (BMSCs) and can maintain normal hematopoiesis. To investigate how leukemic cells inhibit the osteogenic differentiation of BMSCs and the role of Notch signaling in this process, we cocultured BMSCs with acute lymphoblastic leukemia (ALL) cells in osteogenic induction medium. The expression levels of Notch1, Hes1, and the osteogenic markers Runx2, Osteopontin (OPN), and Osteocalcin (OCN) were assessed by real-time RT-PCR and western blotting on day 3. Alkaline phosphatase (ALP) activity was analyzed using an ALP kit, and mineralization deposits were detected by Alizarin red S staining on day 14. And then we treated BMSCs with Jagged1 and anti-Jagged1 neutralizing Ab. The expression of Notch1, Hes1, and the abovementioned osteogenic differentiation markers was measured. Inhibition of the expression of Runx2, OPN, and OCN and reduction of ALP activity and mineralization deposits were observed in BMSCs cocultured with ALL cells, while Notch signal inhibiting rescued these effects. All these results indicated that ALL cells could inhibit the osteogenic differentiation of BMSCs by activating Notch signaling, resulting in a decreased number of osteoblastic cells, which may impair normal hematopoiesis.

Tetramethylpyrazine inhibits the proliferation of acute lymphocytic leukemia cell lines via decrease in GSK-3ß.

Tetramethylpyrazine (TMP) has been proven to be an anticancer agent in many studies. However, its effectiveness in acute lymphoblastic leukemia (ALL) and its molecular mechanisms are still unclear. The present study aimed to evaluate the effect of TMP against Jurkat and SUP-B15 ALL cell lines and to investigate the possible detailed mechanism of action of TMP. A Cell Counting Kit-8 (CCK-8) assay was employed to examine the proliferation of Jurkat and SUP-B15 cells. Flow cytometric analysis was conducted to detect the cell cycle distribution and apoptotic rate. The expression of total glycogen synthase kinase-3ß (GSK-3ß), cox-2, survivin, bcl-2 and p27 RNA and protein levels was detected by quantitative real-time PCR and western blot assay, respectively. Additionally, western blot analysis was used to determine the whole-cell and nuclear protein levels of GSK-3ß downstream transcription factors, NF-κB (p65) and c-myc. TMP inhibited the proliferation of Jurkat and SUP-B15 cells in a dose- and time-dependent manner, with IC50 values of 120 and 200 µg/ml, respectively at 48 h. TMP induced the apoptosis of Jurkat and SUP-B15 cells and synergistically blocked cell cycle progression at the G0/G1 phase. Cells treated with TMP exhibited significantly attenuated GSK-3ß, NF-κB (p65) and c-myc expression, followed by downregulation of bcl-2, cox-2 and survivin and an upregulation of p27. The results showed that TMP induced apoptosis and caused cell cycle arrest in Jurkat and SUP-B15 cells through the downregulation of GSK-3ß, which may have further prevented the induced translocation of NF-κB and c-myc from the cytoplasm to the nucleus.