GP-14 protects against severe hypoxia-induced neuronal injury through the AKT and ERK pathways and its induced transcriptome profiling alteration.

Gypenosides are major bioactive ingredients of G. pentaphyllum. In our previous study, we found that gypenosides had neuroprotective effects against hypoxia-induced injury. In the current study, we focused on the protective effects of gypenoside-14 (GP-14), which is one of the newly identified bioactive components, on neuronal injury caused by severe hypoxia (0.3% O2). The results showed that GP-14 pretreatment alleviated the cell viability damage and apoptosis induced by hypoxia in PC12 cells. Moreover, GP-14 pretreatment also attenuated primary neuron injuries under hypoxic conditions. Additionally, GP-14 pretreatment significantly ameliorated neuronal damage in the hippocampal region induced by high-altitude cerebral edema (HACE). At the molecular level, GP-14 pretreatment reversed the decreased activities of the AKT and ERK signaling pathways caused by hypoxia in PC12 cells and primary neurons. To comprehensively explore the possible mechanisms, transcriptome sequencing was conducted, and these results indicated that GP-14 could alter the transcriptional profiles of primary neuron. Taken together, our results suggest that GP-14 acts as a neuroprotective agent to protect against neuronal damage induced by severe hypoxia and it is a promising compound for the development of neuroprotective drugs.

Multimodal Neuroimaging in Rett Syndrome With MECP2 Mutation.

Rett syndrome (RTT) is a rare neurodevelopmental disorder characterized by severe cognitive, social, and physical impairments resulting from de novo mutations in the X-chromosomal methyl-CpG binding protein gene 2 (MECP2). While there is still no cure for RTT, exploring up-to date neurofunctional diagnostic markers, discovering new potential therapeutic targets, and searching for novel drug efficacy evaluation indicators are fundamental. Multiple neuroimaging studies on brain structure and function have been carried out in RTT-linked gene mutation carriers to unravel disease-specific imaging features and explore genotype-phenotype associations. Here, we reviewed the neuroimaging literature on this disorder. MRI morphologic studies have shown global atrophy of gray matter (GM) and white matter (WM) and regional variations in brain maturation. Diffusion tensor imaging (DTI) studies have demonstrated reduced fractional anisotropy (FA) in left peripheral WM areas, left major WM tracts, and cingulum bilaterally, and WM microstructural/network topology changes have been further found to be correlated with behavioral abnormalities in RTT. Cerebral blood perfusion imaging studies using single-photon emission CT (SPECT) or PET have evidenced a decreased global cerebral blood flow (CBF), particularly in prefrontal and temporoparietal areas, while magnetic resonance spectroscopy (MRS) and PET studies have contributed to unraveling metabolic alterations in patients with RTT. The results obtained from the available reports confirm that multimodal neuroimaging can provide new insights into a complex interplay between genes, neurotransmitter pathway abnormalities, disease-related behaviors, and clinical severity. However, common limitations related to the available studies include small sample sizes and hypothesis-based and region-specific approaches. We, therefore, conclude that this field is still in its early development phase and that multimodal/multisequence studies with improved post-processing technologies as well as combined PET-MRI approaches are urgently needed to further explore RTT brain alterations.

Inhibition of miR-337-3p involved in the protection of CoCl2 -induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway.

OBJECTIVE: To investigate the possibility of microRNA (miR)-337-3p in the protection of hypoxia-induced injury in PC12 cells via modulating the JAK2/STAT3 signaling pathway. METHODS: Dual-luciferase reporter assay analyzed the relationship between the miR-337-3p and JAK2. PC12 cells were divided into normal, CoCl2 , CoCl2 + NC, CoCl2 + inhibitors, CoCl2 + JAK2, and CoCl2 + mimics + JAK2 groups. Then, PC12 cell viability and apoptosis were measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and Annexin-V-fluorescein isothiocyanate/propidium iodide methods. Quantitative real-time polymerase chain reaction and Western blot analysis were used to determine expressions. Besides, the intracellular reactive oxygen species (ROS) was examined by dichloro-dihydro-fluorescein diacetate (DCFH-DA) while the mitochondrial membrane potential (MMP) by using JC-1. RESULTS: The negative targeting relationship between miR-337-3p and JAK2 was confirmed. When compared with the normal group, miR-337-3p was increased while JAK2 and STAT3 were decreased in CoCl2 -induced PC12 cells, with decreased cell viability. Moreover, either miR-337-3p inhibitor or JAK2 overexpression could partially reverse CoCl2 -induced decrease in PC12 cell viability. Besides, CoCl2 could also trigger PC12 cell apoptosis by increasing cleaved caspase 3 and Bax but decreasing Bcl-2 and Bcl-XL, which, however, were abolished with the transfection of miR-337-3p inhibitors or lentivirus transfection to activate JAK2. Compared with the CoCl2 group, the average of fluorescent signals of ROS in the CoCl2 + inhibitors group and the CoCl2 + JAK2 group was lower, while the activities of superoxide dismutase, catalase, glutathione peroxidase, and total anti-oxidative capacity were higher, together with an increase in MMP. CONCLUSION: Inhibiting miR-337-3p could activate the JAK2/STAT3 signaling pathway to suppress CoCl 2 -induced cytotoxicity and apoptosis and ameliorate oxidative stress and MMP in PC12 cells.

Risk Factors and Adverse Pregnancy Outcomes of Succenturiate Placenta: A Case-Control Study.

OBJECTIVE: To identify risk factors associated with succenturiate placenta and to evaluate the association between adverse pregnancy outcomes and succenturiate placenta in singleton pregnancies. STUDY DESIGN: The total population of women (n = 28,256) with singleton pregnancies who delivered in Zhangqiu City Hospital during the study period between 2002 and 2012 was reviewed. Risk factors. and adverse pregnancy outcomes were evaluated separately among women with and without succenturiate placenta by means of χ² and logistic regression analyses. RESULTS: The incidence of succenturiate placenta among women with singleton pregnancies was 1.04% (n = 294 of 28,256). Independent risk factors for succenturiate placenta were gestational age, prepregnancy BMI, pelvic infection, prior cesarean section, infertility, and preeclampsia. The succenturiate placenta was associated with a 1.076-, 1.056-, 12.076-, 1.894-, 5.217-, and 4.814-fold increased risk, respectively, as compared to pregnancies with normal cord insertion. For pregnancy outcome comparisons, cases of premature birth, low birth weight, and 5-minute Apgar score ≤ 7 were higher in cases with succenturiate placenta than in those without succenturiate placenta. The rate of cesarean section was increased. CONCLUSION: The results suggest that the incidence of succenturiate placenta increases along with an increase in pelvic infection, infertility, and preeclampsia. The condition of succenturiate placenta increases the risks for prematurity, impaired fetal growth, and cesarean delivery.

EMMNet: sensor networking for electricity meter monitoring.

Smart sensors are emerging as a promising technology for a large number of application domains. This paper presents a collection of requirements and guidelines that serve as a basis for a general smart sensor architecture to monitor electricity meters. It also presents an electricity meter monitoring network, named EMMNet, comprised of data collectors, data concentrators, hand-held devices, a centralized server, and clients. EMMNet provides long-distance communication capabilities, which make it suitable suitable for complex urban environments. In addition, the operational cost of EMMNet is low, compared with other existing remote meter monitoring systems based on GPRS. A new dynamic tree protocol based on the application requirements which can significantly improve the reliability of the network is also proposed. We are currently conducting tests on five networks and investigating network problems for further improvements. Evaluation results indicate that EMMNet enhances the efficiency and accuracy in the reading, recording, and calibration of electricity meters.

[Dexamethasone up-regulates the expression of glucocorticoid receptor in growth plate and inhibits the longitudinal growth of bone: experiment with rats].

OBJECTIVE: To investigate the regulation of the glucocorticoid of pharmacological doses on the expression of glucocorticoid receptor in growth plate and to explore the mechanism of the direct inhibition of the longitudinal growth of bone by dexamethasone. METHODS: Twenty 3-week-old male weanling SD rats were randomly divided into two groups: dexamethasone group (n = 12), intraperitoneally injected with dexamethasone 200 microg/100 g body weight once a day for 10 days and control group (n = 8), intraperitoneally injected with normal saline of the same volume. Ten days later the rats were killed. The length of the proximal tibia was excised, fixed and decalcified, and then paraffin embedded. Sections of 5 microm thick were cut and processed for histomorphometry The total height of growth plate, height of proliferative zone, and height of hypertrophic zone were determined. RESULTS: The length of tibia, total height of growth plate, height of proliferative zone, and height of hypertrophic zone of the dexamethasone group were 28.9 mm +/- 1.2 mm, 4.01 microm +/- 0.28 microm, 1.98 microm +/- 0.13 microm, and 1.67 microm +/- 0.18 microm respectively, all significantly lower those of the control group (30.5 mm +/- 1.1 mm, 5.53 microm +/- 0.46 microm, 2.25 microm +/- 0.30 microm, and 2.87 microm +/- 0.19 microm respectively, all P < 0.01). The resting chondrocytes and hypertrophic chondrocytes in the growth plates of the rats in the dexamethasone group all expressed glucocorticoid receptor, whereas the proliferating chondrocytes didn't. The absorbance values of the resting chondrocytes and hypertrophic chondrocytes in the growth plates of the dexamethasone group were 0.238 +/- 0.026 and 0.283 +/- 0.042 respectively, both significantly higher than those of the control group (0.187 +/- 0.027 and 0.211 +/- 0.022 respectively, both P < 0.01). CONCLUSION: The glucocorticoid receptors are essential for the longitudinal growth of bone. The glucocorticoid of pharmacological dose inhibits the longitudinal growth of bone by up-regulating the expression of glucocorticoid receptor.