Annexin A2 degradation contributes to dopaminergic cell apoptosis via regulating p53 in neurodegenerative conditions.

BACKGROUND: P53 overexpression has been shown to involve in mitochondria-mediated dapaminergic neuron cell death in Parkinson's disease. However, the exactly molecular mechanisms responsible for the p53-dependent intrinsic cell death in neurodegenerative conditions remain unclearly. Annexin A2 is a multifunctional protein that negatively regulates p53 expression. The purpose of this study was to explore the mechanism of p53 dependent dopaminergic cell death and implication of Annexin A2 in cellular apoptosis in 1-methyl-4-phenylpyridinium (MPP+)-induced PC12 cells. METHODS: The cell viability of neural PC12 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet-razolium bromide assay. Flow cytometry was used to evaluate the apoptosis and mitochondrial transmembrane potential of neural PC12 cells. The expression of p53 and Annexin A2 was analyzed by western blot assay. RESULTS: The present study showed that the exposure of PC12 cells to neurotoxin MPP+ increased the expression levels of p53 and the discharge of mitochondrial transmembrane potential. Notably, Annexin A2 degradation was also observed in this cellular model of Parkinson's disease, in a time and dose-dependent manner. This expressing change of Annexin A2 was in direct proportion to the loss of cell viability of PC12 cells, and this expression pattern was in inverse proportion to p53 levels in this cellular model of Parkinson's disease. CONCLUSION: These results indicated that Annexin A2 degradation plays a crucial role the degeneration of dapaminergic cells of Parkinson's disease, and Annexin A2 downregulation-mediated the cell death is closely associated with mitochondrial dysfunction via p53-dependent pathway; thus provide a novel therapeutic target for Parkinson's disease treatment.

High in vivo antitumor activity of cobalt oxoisoaporphine complexes by targeting G-quadruplex DNA, telomerase and disrupting mitochondrial functions.

Two G-quadruplex ligands: [Co(H-La)2Cl2] (Co1) and [Co(Lb)2][CoCl4]⋅2H2O (Co2) have been synthesized and characterized. Two cobalt oxoisoaporphine complexes exhibited selective cytotoxicity to SK-OV-3/DDP cells than for HL-7702 cells. Cytotoxic mechanism studies indicated that both Co1 and Co2 were telomerase inhibitor targeting c-myc, telomere, and bcl-2 G4s, and triggering cell senescence and apoptosis, which caused S phase arrest. They also induced mitochondrial dysfunction. The better antitumor activity of Co2, which should be correlated with a moiety of 2-[5-(2-pyridinyl)-1H-pyrrol-2-yl]pyridine in the Lb. Importantly, Co2 at high doses showed at least the same level of tumor growth inhibition efficacy compared to that of cisplatin, and better in vivo safety profile.

[Effects of nitrogen application rates on apparent soil nitrogen surplus of late sowing wheat with straw returning in rice-wheat rotation].

Field experiments were conducted to study the effects of varying rates of nitrogen application on soil mineral nitrogen content, amount of nitrogen released from the straw, and grain yield of late sowing wheat with straw returning. The result showed that a high nitrogen fertilizer application rate enhanced the mineral nitrogen content in the soil layer of 0 to 50 cm, and also in the lower soil layers when using N at 270 and 360 kg · hm(-2) with the advance of growth stages. The amount of nitrogen released form the straw increased as the nitrogen application rate increased; the lowest appeared from overwintering to jointing, and the highest from jointing to maturity. During the whole growing season, apparent nitrogen surplus occurred when the nitrogen application rate was higher than 180 kg · hm(-2). The N surplus before jointing was significantly higher than that from jointing to maturity. Grain yield reached the highest at a nitrogen application rate of 270 kg · hm(-2), and a higher application rate obviously decreased the nitrogen use efficiency. It could be concluded that applying nitrogen at 270 kg · him(-2) could improve the grain yield of late sowing wheat with straw returning with the optimal ecological benefit.

Occupational exposure to methylene chloride and risk of cancer: a meta-analysis.

METHODS: We searched MEDLINE and EMBASE for epidemiologic studies on occupational exposure to methylene chloride and risk of cancer. Estimates of study-specific odds ratios (ORs) were calculated using inverse-variance-weighted fixed-effects models and random-effects models. Statistical tests for heterogeneity were applied. RESULTS: We summarized data from five cohort studies and 13 case-control studies. The pooled OR for multiple myeloma was (OR 2.04; 95 % CI 1.31-3.17) in relation to occupational exposure to methylene chloride but not for non-Hodgkin's lymphoma, leukemia, breast, bronchus, trachea and lung, brain and other CNS, biliary passages and liver, prostate, pancreas, and rectum. Furthermore, we focused on specific outcomes for non-Hodgkin's lymphoma and multiple myeloma because of exposure misclassification. The pooling OR for non-Hodgkin's lymphoma and multiple myeloma was 1.42 (95 % CI 1.10-1.83) with moderate degree of heterogeneity among the studies (I (2) = 26.9 %, p = 0.205). CONCLUSIONS: We found an excess risk of multiple myeloma. The non-Hodgkin's lymphoma and leukemia that have shown weak effects should be investigated further.

Bis[4-chloro-2-(quinolin-8-yl-imino-meth-yl)phenolato-κ(3) N,N',O]cobalt(III) trichlorido-methano-lcobaltate(II).

The reaction of 4-chloro-2-(quinolin-8-yl-imino-meth-yl)phenol (HClQP) with cobalt(II) dichloride hexa-hydrate in methanol/chloro-form under solvothermal conditions yielded the title compound, [Co(C16H10ClN2O)2][CoCl3(CH3OH)]. The Co(III) atom is six-coordinated in a slightly distorted octa-hedral geometry by four N atoms and two O atoms of two tridentate HClQP ligands, which are nearly perpendicular to each other, making a dihedral angle of 86.95°. The Co(II) atom is four-coordinated by three Cl atoms and one O atom from a methanol ligand in a distorted tetra-hedral geometry. The crystal packing is consolidated by inter-molecular O-H⋯Cl, C-H⋯Cl and C-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular structure, in which [Co(II)Cl3(CH3OH)] anions are connected via O-H⋯Cl and C-H⋯Cl hydrogen bonds into centrosymmetric dimers. Neighboring cobalt(III) complexes form dimers through C-H⋯O hydrogen bonds, as well as π-π stacking [centroid-centroid distances = 3.30 (2) Å] between the planar quinoline systems of one HClQP ligand and the phenolate ring of another.

[Situation of pesticide poisoning in Huzhou from 2006 to 2009].

OBJECTIVE: To understand the situations of pesticide poisoning in Huzhou and take preventive strategy and measures against the pesticide poisoning. METHODS: Case reports between 2006 and 2009 in the data base of reporting system for occupational diseases were computed by Excel for windows and statistical significance by SPSS12.0. RESULTS: A total of 2298 patients were reported from 2006 to 2009. Among them, the incidence of occupational poisoning accounted for 25.59% (588 cases), including 4 fatalities (fatality rate, 0.68%). Male patients (458 cases, 77.89%) were more than female ones (130 cases, 22.11%) in occupational pesticides poisoning. Summer and autumn were the most seasons in occupational pesticides poisoning occurring. The incidence of non-occupational pesticides poisoning accounted for 74.41% (1710, cases), including 112 fatalities (fatality rate, 6.55%). Female patients (952 cases, 55.67%) were more than male ones (758 cases, 44.33%) in non-occupational pesticides poisoning. 15 - 55 years were the highest incidences among non-occupational pesticides poisoning patients. Insecticides especially organophosphorus insecticides such as methamidophos, parathion, and omethoate comprised a higher proportion, accounting for 79.98% of the pesticides poisoning. CONCLUSION: The incidence and the fatality rate of occupational pesticide poisoning were reduced in the city. However, more attention should be paid to non-occupational pesticides poisoning. To decrease the numbers of pesticide poisoning and the risks of death, the relevant departments should take preventive strategy and measures against the pesticide poisoning.

[Significance of double-oblique multiplanar reconstruction of the treatment decision-making in sacral fracture with sacral neurological damage].

OBJECTIVE: To study diagnostic and surgical significance of the multiplanar reconstruction (MPR) of spiral CT in sacral fracture with sacral neurological damage. METHODS: From April 2007 to April 2009, 10 cases of sacral fracture with sacral neurological damage in Shengjing Hospital of China Medical University were examined by double-oblique MPR of sacrum to show a total length of the sacral neural tube, and observe the course of sacral neural tube and the relationship between fracture and the neural tube. There were 7 males and 3 females, aged 30 - 55 years. The time from injury to hospitalization varied from 1 day to 1 months. The injury was caused by traffic accident in 6 cases, smash of heavy object in 3 cases and crush in 1 cases. All patients were examined with double-oblique MPR (coronal oblique 45 degrees and 30 degrees oblique-shaped bit lost)to display the course of sacral neural tube and the condition of clearly, which was confirmed by operation and clinical validation. RESULTS: The clinical manifestations and international standards for Neurological Classification of Spinal Cord Injury recommended by American Spinal Injury Association International Spinal Cord Society were the basis for clinical diagnose. Nerve injury diagnosed by clinical manifestation were S1 (6 cases), S2 (2 cases), S1 and S2 (2 cases). After double-oblique MPR in patients, we found 3 patients have fractures in sacral neural tube of S1, 1 patients in S2, and 2 patients both in S1 and S2, whom recovered average 12 month after operation (S1 and S2 nerve were pressed by fractures according to operating observation); And there were no fractures in sacral neural tube of other patients (3 cases in S1, 1 cases in S2), these were contund, whom were recovered average 13 month after expectant treatment. CONCLUSIONS: Double-oblique MPR of sacrum has important clinical significance in diagnosis of nature and location with sacral nerve injury, as well as surgical planning. It can be used as routine examination of patients with sacral fracture.

[Experimental expression of HIF-1α in rabbit adipose-derived mesenchymal stem cells by dynamic compression plus IGF-1 gene transfection].

OBJECTIVE: To investigate the effects on HIF-1α expression of rabbit adipose-derived mesenchymal stem cells (ADSCs) by dynamic compression plus IGF-1 gene transfection and explore the mechanism of promoting chondrogenesis by HIF-1α. METHODS: The ADSCs were harvested after the digestion of typeIcollagenase and transfection with pcDNA3.1-IGF-1. And then the cells were seeded onto chitosan/gelatin scaffolds with a density of 5 × 10(7) cells/ml and divided into groups: Group A (control), non-transfected ADSCs; Group B (IGF-1), hIGF-1 gene transfected ADSCs; Group C (loading), untransfected ADSCs with stimulation of compressive loading; Group D (loading + IGF-1), hIGF-1 gene transfected ADSCs and loading stimulation. The dynamic compression was carried out with a bio-reactor at a frequency of 0.1 Hz and a sinusoidal strain amplitude of 2% (2% at 0.1 Hz). The dynamic load was performed every 20 minutes, 4 hours daily. After 7 days, morphological observation was performed. The MTT assay was used to detect the cell proliferation. Meanwhile the CM-DiI cell-labeling solution was used to observe the distribution of cells. The total amount of GAG and the expression of related genes of IGF-1, HIF-1α, type II collagen (COL II) and Sox-9 were quantified. RESULTS: The best morphology was found in loading+ IGF-1 group. The results of proliferating capacity were: Group A < C < B < D (P < 0.01); Dil fluorescence showed that the cells were well-distributed in Group D. Meanwhile, the content of total GAG and the expression of related genes demonstrated: Group A < C < B < D (P < 0.01). And the combined effect was more significant than either alone. CONCLUSION: In three-dimensional culture conditions, dynamic compression plus IGF-1 transfection can significantly enhance the level of autocrine IGF-1. Both of two experimental intervention factors can significantly up-regulate the mRNA level of HIF-1α. And they exert a synergistic effect. HIF-1α plays an important role in promoting the chondrogenesis and the synthesis and secretion of extra-cellular matrix.

[Effects of shading on wheat grain starch quality and redistribution of pre-anthesis stored nonstructural carbohydrates].

This paper studied the effects of shading in the period from jointing to maturity on the grain yield, starch content, and starch paste traits of two winter wheat (Triticum aestivum L.) cultivars, shading-tolerant Yangmai 158 and shading-intolerant Yangmai 11, and analyzed the relationships of the redistribution of total soluble sugars stored before anthesis in vegetative organs with the grain yield, starch content, and starch paste parameters of the cultivars. The results showed that shading decreased the redistribution of pre-anthesis stored total soluble sugars in vegetative organs to reproductive organ, resulting in the decrease of grain yield, and significantly decreased the amylopectin content but had no effects on the amylose content in grains, inducing a significant decrease in the ratio of amylopectin to amylase content in the grains. Shading also decreased the grain starch peak viscosity of the cultivars. Under shading, Yangmai 11 had a decrease of its grain starch through viscosity and an increase of starch pasting temperature, while Yangmai 158 had lesser responses in the two parameters.