MiR-214 protects MC3T3-E1 osteoblasts against H2O2-induced apoptosis by suppressing oxidative stress and targeting ATF4.

OBJECTIVE: Fragility fracture is one of the common complications of osteoporosis. Elevated oxidative stress-induced apoptosis is thought to be one of the unfavorable factors to osteoblastic dysfunction, which increased the risk of bone fracture. However, the molecular mechanisms for oxidative stress-induced osteoblast cells apoptosis still need to be elucidated. This study aims to investigate the protective function of miR-214 in H2O2-induced apoptosis of MC3T3-E1 osteoblasts. MATERIALS AND METHODS: MC3T3-E1 cells were treated with 400 µM H2O2. Flow cytometry was adopted to detect the apoptosis rate; malondialdehyde (MDA) and glutathione peroxidase (Gpx) levels were used to determine the reactive oxygen species (ROS) level. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to test the expression level of miR-214 and ATF4. After transfected MC3T3-E1 cells with miR-214 mimics and inhibitor, RT-PCR was used to detect activating transcription factor 4 (ATF4) expression level. RESULTS: H2O2 treatment increased ROS induced intracellular oxidative injury. Flow cytometry showed that 400 µM H2O2 induced the apoptosis of MC3T3-E1 cells. Moreover, RT-PCR showed decreased expression level of MiR-214. Furthermore, the apoptosis induced by high ROS level was reversed by increased miR-214 expression level. The regulatory ability of MiR-214 to apoptosis is by regulating ATF4 expression. CONCLUSIONS: miR-214 plays a protective role in H2O2 induced MC3T3 osteoblasts apoptosis and its protective effect is proceeded by regulating ROS level and ATF4 expression level.

Domain topology and domain switching kinetics in a hybrid improper ferroelectric.

Charged polar interfaces such as charged ferroelectric walls or heterostructured interfaces of ZnO/(Zn,Mg)O and LaAlO3/SrTiO3, across which the normal component of electric polarization changes suddenly, can host large two-dimensional conduction. Charged ferroelectric walls, which are energetically unfavourable in general, were found to be mysteriously abundant in hybrid improper ferroelectric (Ca,Sr)3Ti2O7 crystals. From the exploration of antiphase boundaries in bilayer-perovskites, here we discover that each of four polarization-direction states is degenerate with two antiphase domains, and these eight structural variants form a Z4 × Z2 domain structure with Z3 vortices and five distinct types of domain walls, whose topology is directly relevant to the presence of abundant charged walls. We also discover a zipper-like nature of antiphase boundaries, which are the reversible creation/annihilation centres of pairs of two types of ferroelectric walls (and also Z3-vortex pairs) in 90° and 180° polarization switching. Our results demonstrate the unexpectedly rich nature of hybrid improper ferroelectricity.

IDH2 mutations are frequent in Chinese patients with acute myeloid leukemia and associated with NPM1 mutations and FAB-M2 subtype.

INTRODUCTION: Gene mutations play an important role in acute myeloid leukemia (AML) pathogenesis. Several genes have been identified in AML, such as FLT3, KIT, NPM1, and JAK2. This study investigated the frequency of novel mutations in IDH1 (amino acid R132) and IDH2 (R140 and R172) and analyzed their impact on disease biology and interaction with other mutations in Chinese patients with de novo AML. METHODS: A total of 195 patients were screened for mutations in the IDH1, IDH2, JAK2 V617F, NPM1, FLT3, and KIT genes, using polymerase chain reaction (PCR)-based and direct sequencing assays. RESULTS: IDH mutations occurred at a considerable frequency of 15.89% in Chinese AML cases; IDH2 R140Q was the most frequent genetic alteration and was associated with older age, normal karyotype, and French-American-British classification M2 at diagnosis. There was a strong association of IDH2 mutation with NPM1 mutations and a trend with FLT3-internal-tandem duplication. CONCLUSION: IDH mutations may be a novel genetic marker in cytogenetically normal AML and may cooperate in leukemogenesis.

Serum retinol-binding protein 4 levels in patients with diabetic retinopathy.

Retinol-binding protein 4 (RBP4) has been reported to be involved in the development of insulin resistance and diabetes. This study was designed to investigate serum levels of RBP4 in patients with type 2 diabetes with and without diabetic retinopathy. Based on ophthalmological examination, 92 patients with type 2 diabetes were divided into three subgroups: those without diabetic retinopathy (NDR; n = 40); those with simple diabetic retinopathy (SDR; n = 37); and those with proliferative diabetic retinopathy (PDR; n = 15). The serum RBP4 level was significantly elevated in individuals with PDR compared with those with NDR or SDR. There was a significant positive correlation between serum RBP4 level and the urine albumin excretion rate (r = 0.219). This study showed that RBP4 may be involved in the process of diabetic retinopathy and may be a novel biomarker for its diagnosis and treatment in diabetic patients.

Relationship between stem cell factor/c-kit expression in peripheral blood and blood pressure.

There is a high prevalence of hypertension and hypertension-related vascular disease in humans. Studies show that the expression of stem cell factor (SCF)/c-kit signalling proteins is relatively high during blood vessel repair. The aim of this study was to investigate the relationship between blood pressure (BP) and the expression of SCF/c-kit in peripheral blood. We carried out a cross-sectional analysis of 141 subjects in the health examination centre of our hospital. Information including waist circumference, BP, plasma glucose and serum lipids for each subject was collected. Endothelin-1 (ET-1) and tumour necrosis factor-alpha (TNF-alpha) levels in peripheral blood were determined by radio-immunity assay. Expression levels of SCF and its receptor, c-kit, in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). We found a positive correlation between plasma SCF/c-kit levels and BP in these patients (SCF: hypertension 907.1+/-52.3 vs pre-hypertension 834.6+/-47.6 vs normal control 768.8+/-44.1 ng l(-1); c-kit: hypertension 13.2+/-1.6 vs pre-hypertension 11.1+/-2.1 vs normal control 9.6+/-1.5 mg l(-1), P<0.01). SCF/c-kit levels were also positively correlated with ET-1 and TNF-alpha levels (ET-1: hypertension 155.5+/-12.1 vs pre-hypertension 142.0+/-11.2 vs normal control 117.9+/-10.3 ng l(-1); TNF-alpha: hypertension 14.7+/-3.9 vs pre-hypertension 11.6+/-4.2 vs normal control 8.1+/-2.8 ng l(-1), P<0.01). Multiple linear regression analyses showed that SCF, c-kit and ET-1 are independent predictors for systolic blood pressure, and that SCF, c-kit, ET-1 and TNF-alpha are independent predictors for diastolic blood pressure. SCF/c-kit levels increase with BP levels are positively correlated with ET-1 and TNF-alpha levels.

Konjak mosaic virus: the complete nucleotide sequence of the genomic RNA and its comparison with other potyviruses.

Konjak mosaic virus (KoMV) belongs to the genus Potyvirus, family Potyviridae. The complete nucleotide sequence of KoMV F isolate (KoMV F) was determined. The genome is 9,544 nucleotides long excluding the 3' terminal poly A tail and encodes a typical potyviral 350-kDa polyprotein of 3,087 amino acids. Phylogenetic analysis using known potyvirus polyproteins shows that KoMV constitutes a branch with yam mosaic virus, close to another branch including Japanese yam mosaic virus, turnip mosaic virus, scallion mosaic virus and lettuce mosaic virus. The 3' terminal 1,842 nucleotides of a different isolate of KoMV, K-2, was also determined, covering the C-terminal 292 amino acids of the nuclear inclusion protein b (NIb), coat protein (CP), and the 3' untranslated region. The amino acid sequences of the KoMV F CP and the nucleotide sequences of the KoMV F 3' untranslated region showed 92.5 and 90.5% identity to the corresponding genes of K-2, 88.7-96.8 and 92.7-94.4% to those of Zantedeschia mosaic virus (ZaMV) isolates, 87.5-89.7% and 85.5-90.3% to those of Japanese hornwort mosaic virus (JHMV) isolates. These results showed that KoMV is a distinct potyvirus and that KoMV, ZaMV, and JHMV are members of the same potyvirus species. Considering that KoMV was the first of these to be described, ZaMV and JHMV may be considered isolates of KoMV.