The Effect of Safflower Yellow on Spinal Cord Ischemia Reperfusion Injury in Rabbits

Safflower yellow (SY) is the safflower extract and is the one of traditional Chinese medicine. The aim of the present work was to investigate the effect of SY on spinal cord ischemia reperfusion injury (SCIRI) in rabbits. The models of spinal cord ischemia reperfusion (SI/R) were constructed, and the degree of the post-ischemic injury was assessed by means of the neurological deficit scores and plasma levels of lipid peroxidation reactioin and neuronal morphologic changes. SCIRI remarkably affected the functional activities of the hind limbs and activated lipid peroxidation reaction. SY could attenuate apoptosis and SCIRI by enhancing Bcl-2 expression and inhibiting Bax and caspase-3 activation

Cross-Regulation between Oncogenic BRAFV600E Kinase and the MST1 Pathway in Papillary Thyroid Carcinoma

BACKGROUND:The BRAF(V600E) mutation leading to constitutive signaling of MEK-ERK pathways causes papillary thyroid cancer (PTC). Ras association domain family 1A (RASSF1A), which is an important regulator of MST1 tumor suppressor pathways, is inactivated by hypermethylation of its promoter region in 20 to 32% of PTC. However, in PTC without RASSF1A methylation, the regulatory mechanisms of RASSF1A-MST1 pathways remain to be elucidated, and the functional cooperation or cross regulation between BRAF(V600E) and MST1,which activates Foxo3,has not been investigated. METHODOLOGY/PRINCIPAL FINDINGS:The negative regulators of the cell cycle, p21 and p27, are strongly induced by transcriptional activation of FoxO3 in BRAF(V600E) positive thyroid cancer cells. The FoxO3 transactivation is augmented by RASSF1A and the MST1 signaling pathway. Interestingly, introduction of BRAF(V600E)markedly abolished FoxO3 transactivation and resulted in the suppression of p21 and p27 expression. The suppression of FoxO3 transactivation by BRAF(V600E)is strongly increased by coexpression of MST1 but it is not observed in the cells in which MST1, but not MST2,is silenced. Mechanistically, BRAF(V600E)was able to bind to the C-terminal region of MST1 and resulted in the suppression of MST1 kinase activities. The induction of the G1-checkpoint CDK inhibitors, p21 and p27,by the RASSF1A-MST1-FoxO3 pathway facilitates cellular apoptosis, whereas addition of BRAF(V600E) inhibits the apoptotic processes through the inactivation of MST1. Transgenic induction of BRAF(V600E)in the thyroid gland results in cancers resembling human papillary thyroid cancers. The development of BRAF(V600E)transgenic mice with the MST1 knockout background showed that these mice had abundant foci of poorly differentiated carcinomas and large areas without follicular architecture or colloid formation. CONCLUSIONS/SIGNIFICANCE:The results of this study revealed that the oncogenic effect of BRAF(V600E) is associated with the inhibition of MST1 tumor suppressor pathways, and that the activity of RASSF1A-MST1-FoxO3 pathways determines the phenotypes of BRAF(V600E) tumors

Glutamate signaling at cytoneme synapses.

We investigated the roles of components of neuronal synapses for development of the Drosophila air sac primordium (ASP). The ASP, an epithelial tube, extends specialized signaling filopodia called cytonemes that take up signals such as Dpp (Decapentaplegic, a homolog of the vertebrate bone morphogenetic protein) from the wing imaginal disc. Dpp signaling in the ASP was compromised if disc cells lacked Synaptobrevin and Synaptotagmin-1 (which function in vesicle transport at neuronal synapses), the glutamate transporter, and a voltage-gated calcium channel, or if ASP cells lacked Synaptotagmin-4 or the glutamate receptor GluRII. Transient elevations of intracellular calcium in ASP cytonemes correlate with signaling activity. Calcium transients in ASP cells depend on GluRII, are activated by l-glutamate and by stimulation of an optogenetic ion channel expressed in the wing disc, and are inhibited by EGTA and by the GluR inhibitor NASPM (1-naphthylacetyl spermine trihydrochloride). Activation of GluRII is essential but not sufficient for signaling. Cytoneme-mediated signaling is glutamatergic

Cytoneme-Mediated Contact-Dependent Transport of the Drosophila Decapentaplegic Signaling Protein

Decapentaplegic (Dpp), a Drosophila morphogen signaling protein, transfers directly at synapses made at sites of contact between cells that produce Dpp and cytonemes that extend from recipient cells. The Dpp that cytonemes receive moves together with activated receptors toward the recipient cell body in motile puncta. Genetic loss-of-function conditions for diaphanous, shibire, neuroglian, and capricious perturbed cytonemes by reducing their number or only the synapses they make with cells they target, and reduced cytoneme-mediated transport of Dpp and Dpp signaling. These experiments provide direct evidence that cells use cytonemes to exchange signaling proteins, that cytoneme-based exchange is essential for signaling and normal development, and that morphogen distribution and signaling can be contact-dependent, requiring cytoneme synapses

miR-425-5p Acts as a Molecular Marker and Promoted Proliferation, Migration by Targeting RNF11 in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and dangerous malignant tumors in China, which causes a large number of deaths every year. MicroRNAs (miRNAs) dysfunction contributes to the malignant progression of tumors. The aim of our study was to investigate the relationship between the biological role of miR-425-5p and malignant progression of HCC. Our results showed that miR-425-5p expression was significantly upregulated in HCC tissues and closely related to the poor prognosis of HCC patients. The knockdown of miR-425-5p inhibited cell proliferation and migration. Further, we identified RNF11 as the downstream target gene of miR-425-5p. In addition, the rescue experiments showed that the upregulation of RNF11 could rescue the inhibitory effect of miR-425-5p on HCC. In general, miR-425-5p as an oncogene promotes the malignant development of HCC via RNF11 and serves as a molecular target for predicting the prognosis of HCC patients

Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits

Ulinastatin (UTI), a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties

Effect of microstructure and reaction medium on photocatalytic performance and stability of BiO catalyst for CO2 reduction

Control the microstructure of the photocatalyst and change the reaction medium have great potential to improve activity and selectivity of a photocatalyst. Herein, we prepared ordered mesoporous and quantum dot BiO with similar grain size, and then studied their CO2 reduction performance under different reaction mediums. The results revealed that the activity, selectivity and stability of a photocatalyst are importantly influenced by reaction medium and microstructure of a photocatalyst. Under the same conditions, quantum dot BiO exhibited higher activity but much lower stability than mesoporous structure. More importantly, it was found gas-solid reaction are more efficient than liquid-solid reaction mode

Fast Cryomediated Dynamic Equilibrium Hydrolysates towards Grain Boundary-Enriched Platinum Scaffolds for Efficient Methanol Oxidation

Although platinum nanocrystals have been considered as potential electrocatalysts for methanol oxidation reaction (MOR) in fuel cells, the large-scale practical implementation has been stagnated by their limited abundance, easy poisoning, and low durability. Here, grain boundary-enriched platinum (GB-Pt) scaffolds are produced in large scale via facilely reducing fast cryomediated dynamic equilibrium hydrolysates of platinum salts. Such plentiful platinum grain boundaries are originated from the fast fusion of short platinum nanowires during reduction of the individually and homogeneously dispersed platinum intermediates. These grain boundaries can provide abundant active sites to efficiently catalyze MOR and meanwhile enable to oxidize the adsorbed poisonous CO during the electrocatalytic process. As a consequence, the as-synthesized GB-Pt scaffolds exhibit an impressively high mass activity of 1027.1 mA mgPt−1 for MOR, much higher than that of commercial Pt/C (345.2 mA mgPt−1), as well as good stability up to 5000 cycles. We are confident that this synthetic protocol can be further extended to synthesize various grain boundary-enriched metal scaffolds with broad applications in catalysis

Characterization and Evaluation of OsLCT1 and OsNramp5 Mutants Generated Through CRISPR/Cas9-Mediated Mutagenesis for Breeding Low Cd Rice

To explore how rice (Oryza sativa L.) can be safely produced in Cd-polluted soil, OsLCT1 and OsNramp5 mutant lines were generated by CRISPR/Cas9-mediated mutagenesis. One of OsLCT1 mutant (lct1×1) and two of OsNramp5 mutants (nramp5×7 and nramp5×9) were evaluated for grain Cd accumulation and agronomic performances. In paddy field soil containing approximately 0.9 mg/kg Cd, lct1×1 grains contained approximately 40% (0.17 mg/kg) of the Cd concentration of the wild type parental line, less than the China National Food Safety Standard (0.20 mg/kg). Both OsNramp5 mutants showed low grain Cd accumulation (< 0.06 mg/kg) in the paddy (approximately 0.9 mg/kg Cd) or in pots in soil spiked with 2 mg/kg Cd. However, only nramp5×7 showed normal growth and yield, whereas the growth of nramp5×9 was severely impaired. The study showed that lct1×1 could be used to produce rice grains safe for human consumption in lightly contaminated paddy soils and nramp5×7 used in soils contaminated by much higher levels of Cd. Keywords: cadmium, rice, OsNramp5, OsLCT1, genome-editing, heavy metal contamination, CRISPR, Cas