Liraglutide regulates proliferation, differentiation, and apoptosis of preosteoblasts through a signaling network of Notch/Wnt/Hedgehog signaling pathways.

OBJECTIVE: This study aims to investigate whether liraglutide can affect proliferation, osteogenic differentiation and serum deprivation-induced apoptosis of preosteoblast cell line MC3T3-E1 through the Notch, Wnt/ß-catenin, and Hedgehog (Hh) signaling pathways. MATERIALS AND METHODS: MC3T3-E1 cells were exposed to different treatments (via Notch inhibitor DAPT, an Hh inhibitor cyclopamine, or serum deprivation) or transfections of different siRNAs (targeting glucagon-like peptide-1 receptor (GLP-1R), ß-catenin, or Gli1) in the presence or absence of 100 nM liraglutide. Cell proliferation, mRNA levels of osteogenic differentiation-related genes, mRNA and protein levels of the Notch and Hh signaling pathway proteins, and apoptosis-related proteins were assessed. RESULTS: Liraglutide significantly increased proliferation of MC3T3-E1 cells, expression levels of the Notch and Hh signaling pathway proteins and ß-catenin, and mRNA levels of osteogenic differentiation-related genes and TCF7L2. Moreover, liraglutide promoted a translocation of ß-catenin, increased a ratio of Bcl-2/Bax proteins, reduced serum deprivation-induced apoptosis of MC3T3-E1 cells, and a ratio of caspase-3/procaspase-3. However, a cotreatment with liraglutide and DAPT reversed the alterations. A cyclopamine treatment and knockdowns of GLP-1R, Gli1, and ß-catenin significantly reduced the expression of Notch proteins. Furthermore, the knockdown of GLP-1R, ß-catenin, or Gli1 significantly increased apoptosis, which could be inhibited by liraglutide. CONCLUSIONS: In summary, liraglutide can promote proliferation and differentiation of MC3T3-E1 cells, and inhibit their serum deprivation-induced apoptosis by activating both the Notch and Hh signaling pathways involving ß-catenin and Gli1. These results provide a therapeutic foundation that patients with diabetes and osteoporosis may be cured with treatments of liraglutide.

Deformability study of breast cancer cells using microfluidics.

Cell deformability is an important biomarker which can be used to distinguish between healthy and diseased cells. In this study, microfluidics is used to probe the biorheological behaviour of breast cancer cells in an attempt to develop a method to distinguish between non-malignant and malignant cells. A microfabricated fluidic channel design consisting of a straight channel and two reservoirs was used to study the biorheological behaviour of benign breast epithelial cells (MCF-10A) and non-metastatic tumor breast cells (MCF-7). Quantitative parameters such as entry time (time taken for the cell to squeeze into the microchannel) and transit velocity (speed of the cell flowing through the microchannel) were defined and measured from these studies. Our results demonstrated that a simple microfluidic device can be used to distinguish the difference in stiffness between benign and cancerous breast cells. This work lays the foundation for the development of potential microfluidic devices which can subsequently be used in the detection of cancer cells.

Statistical optimization of process parameters on biohydrogen production from glucose by Clostridium sp. Fanp2.

Statistically based experimental designs were applied to optimizing process parameters for hydrogen production from glucose by Clostridium sp. Fanp2 which was isolated from effluent sludge of anaerobic hydrogen-producing bioreactor. The important factors influencing hydrogen production, which identified by initial screening method of Plackett-Burman, were glucose, phosphate buffer and vitamin solution. The path of steepest ascent was undertaken to approach the optimal region of the three significant factors. Box-Behnken design and response surface analysis were adopted to further investigate the mutual interaction between the variables and identify optimal values that bring maximum hydrogen production. Experimental results showed that glucose, vitamin solution and phosphate buffer concentration all had an individual significant influence on the specific hydrogen production potential (Ps). Simultaneously, glucose and vitamin solution, glucose and phosphate buffer were interdependent. The optimal conditions for the maximal Ps were: glucose 23.75 g/l, phosphate buffer 0.159 M and vitamin solution 13.3 ml/l. Using this statistical optimization method, the hydrogen production from glucose was increased from 2248.5 to 4165.9 ml H2/l.

High Temperature Terahertz Detectors Realized by a GaN High Electron Mobility Transistor.

In this work, a high temperature THz detector based on a GaN high electron mobility transistor (HEMT) with nano antenna structures was fabricated and demonstrated to be able to work up to 200 °C. The THz responsivity and noise equivalent power (NEP) of the device were characterized at 0.14 THz radiation over a wide temperature range from room temperature to 200 °C. A high responsivity Rv of 15.5 and 2.7 kV/W and a low NEP of 0.58 and 10 pW/Hz0.5 were obtained at room temperature and 200 °C, respectively. The advantages of the GaN HEMT over other types of field effect transistors for high temperature terahertz detection are discussed. The physical mechanisms responsible for the temperature dependence of the responsivity and NEP of the GaN HEMT are also analyzed thoroughly.

catena-Poly[[bis(thiocyanato-N)-lead(II)]-mu-1,2-bis(4-pyridyl)-ethane-N:N'].

In the title coordination polymer, [Pb(NCS)(2)(C(12)H(12)N(2))], the coordination geometry about the Pb(II) atom is a distorted octahedron, composed of two N atoms from bpe ligands [bpe is 1,2-bis(4-pyridyl)ethane], two other N atoms from NCS(-) groups and two neighbouring S atoms through short contacts. The trans-bpe ligands act as bridges between two Pb(II) centres resulting in the formation of a linear chain. The terminal S atoms of the NCS(-) ligands make short contacts with the Pb(II) atom of neighbouring chains to form an infinite two-dimensional polymeric structure.