Synthesis,In Vitro,and Computational Studies of PTP1B Phosphatase Inhibitors Based on Oxovanadium(IV) and Dioxovanadium(V) Complexes

One of the main goals of recent bioinorganic chemistry studies has been to design and synthesize novel substances to treat human diseases. The promising compounds are metal-based and metal ion binding components such as vanadium-based compounds. The potential anticancer action of vanadium-based compounds is one of area of investigation in this field. In this study, we present five oxovanadium(IV) and dioxovanadium(V) complexes as potential PTP1B inhibitors with anticancer activity against the MCF-7 breast cancer cell line, the triple negative MDA-MB-231 breast cancer cell line, and the human keratinocyte HaCaT cell line. We observed that all tested compounds were effective inhibitors of PTP1B, which correlates with anticancer activity. [VO(dipic)(dmbipy)]·2 H₂O (Compound 4) and [VOO(dipic)](2-phepyH)·H₂O (Compound 5) possessed the greatest inhibitory effect, with IC₅₀ 185.4 ± 9.8 and 167.2 ± 8.0 nM, respectively. To obtain a better understanding of the relationship between the structure of the examined compounds and their activity, we performed a computer simulation of their binding inside the active site of PTP1B. We observed a stronger binding of complexes containing dipicolinic acid with PTP1B. Based on our simulations, we suggested that the studied complexes exert their activity by stabilizing the WPD-loop in an open position and limiting access to the P-loop.     

Streptozotocin-Induced Diabetes Causes Changes in Serotonin-Positive Neurons in the Small Intestine in Pig Model

Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter of the central and peripheral nervous systems, predominantly secreted in the gastrointestinal tract, especially in the gut. 5-HT is a crucial enteric signaling molecule and is well known for playing a key role in sensory-motor and secretory functions in the gut. Gastroenteropathy is one of the most clinical problems in diabetic patients with frequent episodes of hyperglycemia. Changes in 5-HT expression may mediate gastrointestinal tract disturbances seen in diabetes, such as nausea and diarrhea. Based on the double immunohistochemical staining, this study determined the variability in the population of 5-HT-positive neurons in the porcine small intestinal enteric neurons in the course of streptozotocin-induced diabetes. The results show changes in the number of 5-HT-positive neurons in the examined intestinal sections. The greatest changes were observed in the jejunum, particularly within the myenteric plexus. In the ileum, both de novo 5-HT synthesis in the inner submucosal plexus neurons and an increase in the number of neurons in the outer submucosal plexus were noted. The changes observed in the duodenum were also increasing in nature. The results of the current study confirm the previous observations concerning the involvement of 5-HT in inflammatory processes, and an increase in the number of 5-HT -positive neurons may also be a result of increased concentration of the 5-HT in the gastrointestinal tract wall and affects the motor and secretory processes, which are particularly intense in the small intestines.     

Combined Optical and MR Bioimaging Using Rare Earth Ion Doped NaYF4 Nanocrystals

Here, novel nanoprobes for combined optical and magnetic resonance (MR) bioimaging are reported. Fluoride (NaYF₄) nanocrystals (20–30 nm size) co‐doped with the rare earth ions Gd³⁺ and Er³⁺/Yb³⁺/Eu³⁺ are synthesized and dispersed in water. An efficient up‐ and downconverted photoluminescence from the rare‐earth ions (Er³⁺ and Yb³⁺ or Eu³⁺) doped into fluoride nanomatrix allows optical imaging modality for the nanoprobes. Upconversion nanophosphors (UCNPs) show nearly quadratic dependence of the photoluminescence intensity on the excitation light power, confirming a two‐photon induced process and allowing two‐photon imaging with UCNPs with low power continuous wave laser diodes due to the sequential nature of the two‐photon process. Furthermore, both UCNPs and downconversion nanophosphors (DCNPs) are modified with biorecognition biomolecules such as anti‐claudin‐4 and anti‐mesothelin, and show in vitro targeted delivery to cancer cells using confocal microscopy. The possibility of using nanoprobes for optical imaging in vivo is also demonstrated. It is also shown that Gd³⁺ co‐doped within the nanophosphors imparts strong T1 (Spin‐lattice relaxation time) and T2 (spin‐spin relaxation time) for high contrast MR imaging. Thus, nanoprobes based on fluoride nanophosphors doped with rare earth ions are shown to provide the dual modality of optical and magnetic resonance imaging.     

Role of mitochondria in the switch mechanism of the cell death mode from apoptosis to necrosis--studies on rho0 cells

Detailed mechanisms of the switch of the cell death mode from apoptosis to necrosis remain to be solved, although the intracellular level of ATP and that of free radicals have been postulated to be the major factors involved in the mechanisms. In the present study menadione (MEN)-induced cell injury processes were studied using rho0 cells derived from human osteosarcoma 143B cells and parental rho+ cells co-treated with inhibitors of electron transfer chain of mitochondria or oligomycin, an inhibitor of ATP synthesis. Treatment of rho+ cells with 100 microM MEN induced apoptosis, which reached the maximum at 6 h, and was followed by an abrupt decrease thereafter, while necrotic cells (NC) increased continuously when they were judged by Annexin V and PI double staining. On the other hand, MEN induced apoptotic and necrotic changes much faster in rho0 cells compared to rho+ cells. The frequency to find apoptotic cells (AP) in the former cells was distinctly smaller than that to find NC judged by Annexin V and PI double staining. Electron microscopically, a major population of rho0 cells treated with MEN for 6 h consisted of intermediate cells, and a small number of AP co-existed. At 9 h of the treatment intermediate cells were exclusively seen, and AP were hardly detected. When parental rho+ cells were treated with MEN in the presence of oligomycin or oligomycin plus antimycin A both apoptotic and necrotic changes of the cells were distinctly accelerated. The intracellular level of superoxide in rho0 cells continuously increased after the MEN treatment, whereas that of ATP remained distinctly low before and after the MEN treatment compared to that in rho+ cells. These data suggest that the intracellular level of superoxide may be a key factor controlling the switch from apoptosis to necrosis.     

用户身份管理策略研究

In recent years there has been a fast grow of various electronic services.Each service requires specif-ic credentials for authenticating and authorizing user ac-cess or specific subset of user's personal information for transactions the service offers.Such a situation causes problems with remembering multiple,service-specific authentication data,with controlling user's personal data spread across different services-problems with managing user's identities.This paper is an overview on Identity Management(IdM...     

An Image Super-Resolution Reconstruction Method with Single Frame Character Based on Wavelet Neural Network in Internet of Things

Mobile Networks and Applications - The application of the traditional single frame character image super-resolution reconstruction method has some problems, such as noise can not be removed...     

Ion sensitive field effect transistor modelling for multidomain simulation purposes

The proper design and simulation of modern electronic microsystems oriented towards environment monitoring requires accurate models of various ambient sensors. In particular, this paper presents a comprehensive model of an ion sensitive field effect transistor (ISFET). The model can be employed straightforwardly for simulations at device, circuit or system level.First, the model was validated with electrical measurements and simulations of real structures performed for different ion concentration and temperature values. Then, the ISFET sensor model was employed for mixed-signal simulations in VHDL-AMS, when the analysis of a microsystem consisting of the ISFET sensor and a sigma-delta analogue-to-digital converter was carried out. Additionally, the presence of other ions than hydrogen in the measured solution was also taken into account in the simulations.     

Modification of physicochemical properties of actin filaments suppresses cell fragmentation in the execution phase of staurosporine-induced apoptotic processes

Effects of jasplakinolide (JSP), a stabilizer of F-actin, and latrunculin A (LTA), a destabilizer of F-actin, on a series of events occurring in the execution phase of staurosporine (STS)-induced apoptotic processes were studied using human osteosarcoma 143B cells. Time-dependent apparent increases of the population of cells with collapsed membrane potential of mitochondria (Delta Psi(m)) caused by STS treatment were not due to actual decreases in the Delta Psi(m) per cell, but due to the fragmentation of cells resulting in decreases in the number of active mitochondria per cell. Decreases in the Delta Psi(m) in fragmented cells occurred late in the execution phase. Both JSP and LAT failed to prevent STS-induced release of cytochrome c from mitochondria followed by the activation of caspases 3 and 9, the cleavage of poly (ADP-ribose) polymerase (PARP) and apoptotic nuclear fragmentation. However, both drugs prevented STS-induced apoptotic cell fragmentation and decreases in the Delta Psi(m). These results indicate that physicochemical states of actin filaments play a certain role in the execution phase of STS-induced apoptotic processes.