3,4­Dihydroxyacetophenone attenuates oxidative stress­induced damage to HUVECs via regulation of the Nrf2/HO­1 pathway.

It has been reported that oxidative stress plays a prominent role in diabetic macrovascular diseases. 3,4­Dihydroxyacetophenone (3,4­DHAP) has been found to have a variety of biological activities. However, few studies have assessed the antioxidant capacity of 3,4­DHAP and the underlying mechanisms. Thus, the aim of the present study was to explore the effects of 3,4­DHAP on oxidative stress in human umbilical vein endothelial cells (HUVECs). HUVECs were pre­treated with 3,4­DHAP and then exposed to high glucose conditions. Cell viability and cytotoxicity were measured using an MTT assay. Reactive oxygen species (ROS) levels were measured using an inverted fluorescence microscope and a fluorescent enzyme labeling instrument. Protein expression levels of nuclear factor E2­related factor 2 (Nrf2), heme oxygenase­1 (HO­1), microtubule­associated protein 1A/1B­light chain 3 (LC3) and poly ADP­ribose polymerase­1 (PARP­1) were measured using western blotting, and mRNA expression of Nrf2 and HO­1 were measured through reverse transcription­quantitative PCR (RT­qPCR). Nrf2 nuclear translocation was evaluated using immunofluorescence analysis and autophagosomes were observed using transmission electron microscope (TEM). The results of the present study demonstrated that compared with the control group, cell viability of the high glucose group was reduced and cell cytotoxicity of the high glucose group was increased. ROS production in the high glucose group was clearly enhanced. In addition, high glucose upregulated Nrf2 and HO­1 protein and mRNA expression levels. Nuclear translocation of Nrf2 in the high glucose group was also increased. The formation of autophagosomes in the high glucose group was also higher than that in the control group. Furthermore, LC3­II/LC3­I and PARP­1 protein expression levels were increased after treatment with high glucose. However, compared to the high glucose group, 3,4­DHAP (10 µmol/l) significantly enhanced cell viability. 3,4­DHAP markedly decreased the production of ROS, increased Nrf2 and HO­1 protein and mRNA expression levels, and promoted nuclear translocation of Nrf2 in HUVECs. In addition, 3,4­DHAP promoted the formation of autophagosomes, and notably increased the protein expression levels of LC3­II/LC3­I and PARP­1. Moreover, it was determined that compared to the 3,4­DHAP group, treatment with 3,4­DHAP and ML385 enhanced cell viability, and decreased ROS production, Nrf2 and HO­1 protein and mRNA expression levels, nuclear translocation of Nrf2, and LC3­II/LC3­I and PARP­1 protein expression levels. Collectively, the results of the present study showed that 3,4­DHAP protected HUVECs against oxidative stress via regulation of the Nrf2/HO­1 pathway, by increasing autophagy and promoting DNA damage repair.

Circular RNA circ_0005774 contributes to proliferation and suppresses apoptosis of acute myeloid leukemia cells via circ_0005774/miR-192-5p/ULK1 ceRNA pathway.

Circular RNAs (circRNAs) and microRNAs (miRNAs) have been emerging as new players in acute myeloid leukemia (AML). Hsa_circ_0005774 (circ_0005774) is an upregulated circRNA in pediatric AML, while its role is uncovered. Thus, we intended to measure the function and mechanism of circ_0005774 in AML leukemogenesis. Real time-quantitative PCR revealed that circ_0005774 was highly expressed in blood of pediatric AML patients and AML cells (HL-60 and NB4), accompanied with downregulated miRNA-192-5p (miR-192-5p) which was a crucial tumor-associated and leukemia-related miRNA. Circ_0005774 was abundant in miRNA response element according to CSCD software, and miR-192-5p was identified as a target of circ_0005774, as evidenced by RNA immunoprecipitation and dual-luciferase reporter assays. Cell viability assay, flow cytometry and western blotting were performed to measure cell functions. Accordingly, blocking circ_0005774 and/or overexpressing miR-192-5p could enhance apoptosis rate of HL-60 and NB4 cells, but suppress cell viability and cell cycle entrance, accompanied with depression of proliferation markers including proliferating cell nuclear antigen (PCNA), CyclinD1 and B cell lymphoma 2 (Bcl-2). Meanwhile, depleting miR-192-5p counteracted the role of circ_0005774 knockdown in AML cells. Uncoordinated 51-like kinase 1 (ULK1) was previously demonstrated to be associated with diagnosis, prognosis and therapeutic strategy for AML, and restoring ULK1 could abrogate miR-192-5p overexpression-induced effects in HL-60 and NB4 cells. Notably, ULK1 was a downstream target of miR-192-5p and indirectly modulated by circ_0005774. In conclusion, circ_0005774 knockdown repressed cell proliferation and promoted apoptosis of AML cells partially through regulating miR-192-5p/ULK1 axis.

[Effects of umbilical cord blood monocytes transplantation on EPO protein and oligodendrocyte progenitors in neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: To study the effects of umbilical cord blood monocytes (UCBMC) transplantation on erythropoietin (EPO) protein and oligodendrocyte progenitor cells in hypoxia-ischemia (HI) neonatal rats. METHODS: Forty seven-day-old Sprague-Dawley rats were randomly divided into normal control (N), HI, UCBMC and HI+UCBMC groups (n=10 each). Hypoxic-ischemic brain damage (HIBD) model was prepared according to the Rice method. Twenty-four hours after hypoxia, the N and HI groups were injected with 2 µL phosphate buffered saline (PBS), and the UCBMC and HI+UCBMC groups were injected with 3×10(6) UCBMC via the lateral ventricle. EPO protein and oligodendrocyte progenitor cells in the subventricular zone of the injured brain were observed by EPO/DAPI and NG2/DAPI immunofluorescence double staining, and their correlation was analyzed. RESULTS: Seven days after transplantation, there were more NG2(+)DAPI(+) and EPO(+)DAPI(+) cells in the HI+UCBMC group than in the UCBMC (P<0.05), N and HI groups (P<0.01). More NG2(+)DAPI(+) and EPO(+)DAPI(+) cells were observed in the UCBMC group compared with the N and HI groups (P<0.01). There were more NG2(+)DAPI(+) cells in the N group than in the HI group (P<0.01). The number of NG2(+)DAPI(+) cells was correlated with the number of EPO(+)DAPI(+) cells in the HI+UCBMC group (r=0.898, ß=1.4604, P<0.01). CONCLUSIONS: UCBMC can promote expression of oligodendrocyte progenitor cells, which is correlated with an increase in EPO protein and thus repairs brain white matter damage in neonatal rats with HIBD.

Environmental risk factors for congenital heart disease in the Shandong Peninsula, China: a hospital-based case-control study.

BACKGROUND: In China, and in Shandong province, the proportionate contribution of birth defects to infant mortality has increased, and congenital heart disease (CHD) is now the most common cause of birth defects. The cause of approximately 90% of cases of congenital heart disease is multifactorial. Little is known about modifiable environmental risk factors or regional differences. We investigated putative environmental risk factors for congenital heart disease in the Shandong province of China in order to improve prevention of CHD. METHODS: We conducted a hospital-based 1:2 matched case-control study of 164 patients with congenital heart diseases and 328 controls, all of whom were retrospectively interviewed. Univariate and multivariate analyses were conducted to identify environmental risk factors for CHD. RESULTS: The environmental risk factors associated with CHD were mother's education level (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.15-0.67), neonatal asphyxia or hypoxia (OR, 3.74; 95% CI, 1.25-11.18), number of previous pregnancies (OR, 2.68; 95% CI, 1.44-4.97), maternal upper respiratory tract infection (OR, 4.12; 95% CI, 1.56-10.85), maternal infection (OR, 7.98; 95% CI, 2.14-29.72), maternal B-mode ultrasound examination (OR, 4.05; 95% CI, 1.48-11.08), and maternal mental stress (OR, 3.93; 95% CI, 1.94-7.94) during early pregnancy. No significant interactions were observed among these factors. CONCLUSIONS: Augmenting maternal mental healthcare, obtaining regular health counseling and testing during pregnancy, preventing upper respiratory tract infections, limiting medication during early pregnancy, offering health promotion and health education to women of childbearing age (especially those with less formal education), and improving obstetric procedures and techniques may lower the occurrence of congenital heart disease.

[Relationship of variation 3057 G-->A of exon 20 of leptin receptor gene to lipid metabolism and fat distribution of children with obesity].

OBJECTIVE: To assess the relationship of the variation of exon 20 of leptin receptor (LEPR) gene to the lipid metabolism and fat distribution of the children with obesity. METHODS: Polymerase chain reaction-restriction fragment length polymorphism(RFLP) and polyacrylamide gel electrophoresis were used to analyze the variation of exon 20 of the LEPR gene of the obesity group(72 obesity children) and the control group(60 healthy children). At the same time, all childrens' serum triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), height and weight were measured, and their body mass index(BMI) and fat percent(%fat) were calculated. RESULTS: Three genotypes of exon 20 of LEPR gene were detected in this study. Compared with the control, the frequency of gene variation at 3057 nucleotide G-->A transversion was higher(P<0.05). The concentration of serum TG and the BMI and %fat of the A/A genotype obesity children were higher than those of the G/G genotype ones(P<0.01) but the level of serum HDL of the A/A children were lower than that of the G/G children (P<0.01). As to the G/A genotype children, only their serum TG level was higher than that of the G/G genotype ones(P<0.05). CONCLUSION: The above findings indicated there were polymorphisms in the children with obesity, and those polymorphisms might remarkably affect their lipid metabolism and fat distribution.