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Osteoarthritis is a common degenerative disease in which endoplasmic reticulum stress(ER stress) plays an important role in the pathogenesis of chondrocyte apoptosis. To limit the adverse effects of endoplasmic reticulum stress, cells activate the unfolded protein response (UPR). However, when endoplasmic reticulum stress persists beyond the maximum tolerance of UPR, cells may trigger endoplasmic reticulum dysfunction through three pathways of UPR leading to chondrocyte apoptosis.

In the paper, Poisson-Gamma mixture process is first brought forward, which is dynamically expanded from the well-known Poisson-Gamma mixture model. Some properties on Poisson-Gamma mixture process are presented, including the distribution of increment, Markov property, infinitesimal generator, joint density function of jump/waiting times, and the limit distribution of compound Poisson-Gamma mixture process, etc., which provide a thorough grounding in application of Poisson-Gamma mixture process. At last, some premium calculation principles are presented to show the application of Poisson-Gamma mixture process, which include expected value premium, stop-loss premium, mean-variance premium, and exponential premium. [ABSTRACT FROM AUTHOR]

Aims: Recent studies have reported that intracellular calcium (Ca2+) mobilization is involved in homocysteine (Hcy)-induced endothelial dysfunction and the Na+/H+ exchanger (NHE) is responsible for an increase in the intracellular Ca2+ concentration in cardiovascular disease. We hypothesized that inhibition of the NHE had protective effects on Hcy-induced endothelial dysfunction. Methods: Acetylcholine-induced endothelium-dependent relaxation (EDR) and biochemical parameters were measured in the rat isolated aorta. The level of reactive oxygen species (ROS) was designed by a specific fluorescent probe. The phosphorylation of the nuclear factor-κB (NF-κB) system was studied by Western blot. Results: Cariporide significantly prevented Hcy-impaired EDR and increased nitric oxide (NO) release; endothelial NO synthase activity simultaneously decreased ROS production. We also found that cariporide blocked Hcy-induced NF-κB activation and inhibitor-κB degradation, thus inhibiting the production of tumor necrosis factor-α and intercellular adhesion molecule-1. Conclusions: The mechanisms of protective effects of cariporide may be related to the inhibition of NHE and the decrease in oxidative stress and inflammatory injury. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: The association between diabetes and neointimal expansion after vascular injury has been attributed to the accumulation of advanced glycation end products (AGEs). Here we investigated the inhibitory effect of cariporide, a specific Na+/H+ exchanger 1 blocker, on neointimal proliferation induced by AGEs in a balloon injury model. Methods: Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase (MMP) was monitored by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. The level of reactive oxygen species (ROS) was determined by specific fluorescent probe. The phosphorylation of the nuclear factor-ĸB (NF-ĸB) system was studied by Western blot. Results: Cariporide significantly suppressed AGE-induced neointimal hyperplasia, vascular smooth muscle cell (VSMC) proliferation, COX-2, MMP-2 and MMP-9 expression. In addition, cariporide decreased AGE-induced ROS, malondiadehyde level and increased the superoxide dismutase and glutathione peroxidase activity. We also found that cariporide blocked AGE-induced NF-ĸB activation and inhibitor-ĸB degradation. Conclusions: The results indicated that cariporide inhibited AGE-induced neointimal formation by suppressing the VSMC proliferation and the up-regulation of COX-2, MMP-2, MMP-9 via inhibiting ROS and NF-ĸB activation. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: Accumulation of advanced glycation end products (AGEs) plays a pivotal role in the mechanism by which aging contributes to osteoarthritis (OA). In the present study, we examined the effect of curcumin, a pharmacologically safe phytochemical agent, on AGE-induced tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-13 (MMP-13) in rabbit chondrocytes. Methods: Chondrocytes were derived from rabbit articular cartilage by enzymatic digestion. TNF-α and MMP-13 mRNA was monitored by RT-PCR. TNF-α protein was determined using cytokine-specific ELISA. The reactive oxygen species was determined by the fluorescent probe 29,79-dichlorofluorescein diacetate. The phosphorylation and nuclear translocation of the nuclear factor-ĸB (NF-ĸB) system were studied by Western blot and immunofluorescence respectively. Results: Curcumin significantly decreased AGE-stimulated TNF-α and MMP-13 mRNA and suppressed the NF-ĸB activation via inhibition of ĸBα (I-ĸBα) phosphorylation, I-ĸBα degradation and p65 nuclear translocation. Conclusions: These novel pharmacological actions of curcumin on AGE-stimulated chondrocytes provide new suggestions that curcumin has nutritional potential as a naturally occurring anti-inflammatory agent for treating OA. [ABSTRACT FROM AUTHOR]

Abstract: In this present study, we examined the role of Na+/H+ exchanger 1 (NHE1) in the cultured rat vascular smooth muscle cell (VSMC) proliferation induced by advanced glycation end products (AGEs). AGEs significantly increased the [3H] thymidine incorporation of VSMC. Cariporide, an NHE1 inhibitor, dose-dependently attenuated the AGEs-induced increase in cell DNA synthesis. Thus the effect of AGEs on NHE1 activity was next examined. The cariporide-dependent intracellular pH (pHi) was significantly increased after 24h exposure to AGEs (10μg/ml). The direct AGEs-induced NHE1 activation was measured by the Na+-dependent intracellular pH recovery from intracellular acidosis. AGEs can increase the NHE1 activity in a time- and concentration-dependent manner. Inhibition of either the receptor for AGEs (RAGE) by anti-RAGE or mitogen-activated protein kinases (MAPK) by PD98059 reversed the effect of AGEs on NHE1 activity. Reverse transcription (RT)-PCR analysis revealed that AGEs dose-dependently increased NHE1 mRNA at 24h. These findings demonstrate NHE1 is required for in AGEs-induced proliferation of VSMC, and AGEs increase NHE1 activity via the MAPK pathway. [Copyright &y& Elsevier]

In the paper, p-moment stability of stochastic differential equations with jumps is considered. First, some preliminary notes are given. Then, several theorems on p-moment stability of these equations are established using Liapunov function. At last, an example is present to show application of the obtained results. [Copyright &y& Elsevier]

We investigated the effect of paraoxon on vascular contractility using organ baths in thoracic aortic rings of rabbits and examined the effect of paraoxon on calcium homeostasis using a whole-cell patch-clamp technique in isolated aortic smooth muscle cells of rabbits. The findings show that administration of paraoxon (30 microM) attenuated thoracic aorta contraction induced by phenylephrine (1 microM) and/or a high K+ environment (80 mM) in both the presence and absence of thoracic aortic endothelium. This inhibitory effect of paraoxon on vasoconstrictor-induced contraction was abolished in the absence of extracellular Ca2+, or in the presence of the Ca2+ channel inhibitor, verapamil. But atropine had little effect on the inhibitory effect of paraoxon on phenylephrine-induced contraction. Paraoxon also attenuated vascular smooth muscle contraction induced by the cumulative addition of CaCl2 and attenuated an increase of intracellular Ca2+ concentration induced by K+ in vascular smooth muscle cells. Moreover, paraoxon (30 microM) inhibited significantly L-type calcium current in isolated aortic smooth muscle cells of rabbits. In conclusion, our results demonstrate that paraoxon attenuates vasoconstrictor-induced contraction through inhibiting Ca2+ influx in the rabbits thoracic aorta.