Regulatory Effects and Mechanism of Action of Green Tea Polyphenols on Osteogenesis and Adipogenesis in Human Adipose Tissue-Derived Stem Cells

We previously showed that green tea polyphenols (GTPs) exert antiadipogenic effects on preadipocyte proliferation. Here, we investigated the regulatory effects of GTPs on osteogenesis and adipogenesis during early differentiation of human adipose tissue-derived stem cells (hADSC). Adipogenesis of hADSCs was determined by oil-red-O staining and triglycerides synthesis measurement. Osteoporosis of hADSC was measured using alkaline phosphatase assays and intracellular calcium levels. Immunofluorescence staining and qRT-PCR were used to detect PPARγ-CEBPA regulated adipogenic pathway regulated by PPAR-CEBPA and the osteogenic pathway mediated by RUNX2-BMP2. We found that GTPs treatment significantly decreased lipid accumulation and cellular triglyceride synthesis in mature adipocytes and attenuated pioglitazone-induced adipogenesis in a dose-dependent manner. GTPs downregulated protein and mRNA expression of Pparγ and attenuated pioglitazone-stimulated-Cebpa expression. GTPs treatment significantly enhanced hADSCs differentiation into osteoblasts compared to control and pioglitazone-treated cells. GTPs upregulated RunX2 and Bmp2 proteins and mRNA expression compared to control and significantly attenuated decreased RunX2 and Bmp2 mRNA expression by pioglitazone. In conclusion, our data demonstrates GTPs possesses great ability to facilitate osteogenesis and simultaneously inhibits hADSC differentiation into adipogenic lineage by upregulating the RUNX2-BMP2 mediated osteogenic pathway and suppressing PPARγ-induced signaling of adipogenesis. These findings highlight GTPs’ potential to combat osteoporosis associated with obesity.     

海水中Cu、Zn离子对牟氏角毛藻生长的生态效应

研究了Ｃｕ、Ｚｎ离子对车氏角毛藻生长的生态效应．结果表明,Ｃｕ离子活度低于１０－７．８０ｍｏｌ·Ｌ－１时,角毛藻生长繁殖良好,其中以１０－１３．５７～１０－１０．５２ｍｏｌ·Ｌ－１为最好;Ｃｕ离子活度≥１０－７．８０ｍｏｌ·Ｌ－１时产生毒性．低Ｚｎ离子活度未表现出对车氏角毛藻的必需性,Ｚｎ离子活度＞１０－７．００ｍｏｌ·Ｌ－１时不利于生长繁殖．与Ｚｎ离子相比,牟氏角毛藻对Ｃｕ离子的毒性更为敏感．     

Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor site 4 and induce a negative shift in the voltage dependence of activation through a voltage sensor-trapping mechanism. Kinetic analysis showed that beta-scorpion toxin binds to the resting state, and subsequently the bound toxin traps the voltage sensor in the activated state in a voltage-dependent but concentration-independent manner. The rate of voltage sensor trapping can be fit by a two-step model, in which the first step is voltage-dependent and correlates with the outward gating movement of the IIS4 segment, whereas the second step is voltage-independent and results in shifted voltage dependence of activation of the channel. Mutations of Glu(779) in extracellular loop IIS1-S2 and both Glu(837) and Leu(840) in extracellular loop IIS3-S4 reduce the binding affinity of beta-scorpion toxin. Mutations of positively charged and hydrophobic amino acid residues in the IIS4 segment do not affect beta-scorpion toxin binding but alter voltage dependence of activation and enhance beta-scorpion toxin action. Structural modeling with the Rosetta algorithm yielded a three-dimensional model of the toxin-receptor complex with the IIS4 voltage sensor at the extracellular surface. Our results provide mechanistic and structural insight into the voltage sensor-trapping mode of scorpion toxin action, define the position of the voltage sensor in the resting state of the sodium channel, and favor voltage-sensing models in which the S4 segment spans the membrane in both resting and activated states.     

An adenosine A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats

The adenosine A(2A) receptor (A(2A)R) has been demonstrated to play a crucial role in the regulation of the sleep process. However, the molecular mechanism of the A(2A)R-mediated sleep remains to be elucidated. Here we used electroencephalogram and electromyogram recordings coupled with in vivo microdialysis to investigate the effects of an A(2A)R agonist, CGS21680, on sleep and on the release of histamine and GABA in the brain. In freely moving rats, CGS21680 applied to the subarachnoid space underlying the rostral basal forebrain significantly promoted sleep and inhibited histamine release in the frontal cortex. The histamine release was negatively correlated with the amount of non-rapid eye movement sleep (r = - 0.652). In urethane-anesthetized rats, CGS21680 inhibited histamine release in both the frontal cortex and medial pre-optic area in a dose-dependent manner, and increased GABA release specifically in the histaminergic tuberomammillary nucleus but not in the frontal cortex. Moreover, the CGS21680-induced inhibition of histamine release was antagonized by perfusion of the tuberomammillary nucleus with a GABA(A) antagonist, picrotoxin. These results suggest that the A(2A)R agonist induced sleep by inhibiting the histaminergic system through increasing GABA release in the tuberomammillary nucleus.     

A Robust and Accurate Two-Step Auto-Labeling Conditional Iterative Closest Points (TACICP) Algorithm for Three-Dimensional Multi-Modal Carotid Image Registration

Atherosclerosis is among the leading causes of death and disability. Combining information from multi-modal vascular images is an effective and efficient way to diagnose and monitor atherosclerosis, in which image registration is a key technique. In this paper a feature-based registration algorithm, Two-step Auto-labeling Conditional Iterative Closed Points (TACICP) algorithm, is proposed to align three-dimensional carotid image datasets from ultrasound (US) and magnetic resonance (MR). Based on 2D segmented contours, a coarse-to-fine strategy is employed with two steps: rigid initialization step and non-rigid refinement step. Conditional Iterative Closest Points (CICP) algorithm is given in rigid initialization step to obtain the robust rigid transformation and label configurations. Then the labels and CICP algorithm with non-rigid thin-plate-spline (TPS) transformation model is introduced to solve non-rigid carotid deformation between different body positions. The results demonstrate that proposed TACICP algorithm has achieved an average registration error of less than 0.2mm with no failure case, which is superior to the state-of-the-art feature-based methods.