These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.
Aim: To explore the action of doxorubicin on vascular smooth muscle cells. Methods: Isometric tension of denuded or intact thoracic aortic vessels was recorded and [Ca 2+ ] i in isolated aortic smooth muscle cells was measured by using Fluo-3. Results: Doxorubicin induced phasic and tonic contractions in denuded vessels and increased levels of [Ca 2+ ] i in single muscle cells. Treatment with 10 µmol/L ryanodine had no effect on basal tension, but it did abolish doxorubicin-induced phasic contraction. Treatment with 10 mmol/L caffeine induced a transient phasic contraction only, and the effect was not significantly altered by ryanodine, the omission of extracellular Ca 2+ or both. Phenylephrine induced rhythmic contraction (RC) in intact vessels. Treatment with 100 µmol/L doxorubicin enhanced RC amplitude, but 1 mmol/L doxorubicin abolished RC, with an increase in maximal tension. Caffeine at 100 µmol/L increased the frequency of the RC only. In the presence of 100 µmol/L caffeine, however, 100 µmol/L doxorubicin abolished the RC and decreased its maximal tension. Treatment with 10 µmol/L ryanodine abolished the RC, with an increase in the maximal tension. In Ca 2+ -free solution, doxorubicin induced a transient [Ca 2+ ] i increase that could be abolished by ryanodine pretreatment in single muscle cells. The doxorubicin-induced increase in [Ca 2+ ] i was suppressed by nifedipine and potentiated by ryanodine and charybdotoxin. Conclusion: Doxorubicin not only releases Ca 2+ from the sarcoplasmic reticulum but also promotes the entry of extracellular Ca 2+ into vascular smooth muscle cells.
Purpose: To investigate whether the total triterpenoids extracted from Psidium Guajava leaves (TTPGL) attenuate the development of diabetic peripheral neuropathy in rats by
Oxidative stress has been suggested to play a causative role in the development of obesity-induced insulin resistance and type 2 diabetes. Given the antioxidant potency of previously reported xanthones isolated from Swertia mussotii. These natural products were further evaluated against other targets in diabetes, aldose reductase and α-glucosidase, in order to identify novel multitarget-directed antidiabetic agents. Among the 14 xanthones screened, 1,3,7,8-tetrahydroxyxanthone (6), 1,3,5,8-tetrahydroxyxanthone (7), and 2,3,6,8-tetrahydroxyxanthone-7C-(β-D-glucoside) (12) were confirmed as good antioxidants and α-glucosidase inhibitors. Xanthone 7 was also confirmed as a potent inhibitor of aldose reductase (ALR2). Xanthone 7 was the most active α-glucosidase and ALR2 inhibitor, with IC50 values of 5.2±0.3 μM and 88.6±1.6 nM, respectively, while compound 12 was shown to be the most active antioxidant. Given the overall profile, xanthone 7 is considered to be the most promising multitarget antidiabetic agent, and may have potential for the treatment of both diabetes and diabetic complications.
Inspired by the mechanism of generation and restriction among five elements in Chinese traditional culture, we present a novel Multi-Objective Five-Elements Cycle Optimization algorithm (MOFECO). During the optimization process of MOFECO, we use individuals to represent the elements. At each iteration, we first divide the population into several cycles, each of which contains several individuals. Secondly, for every individual in each cycle, we judge whether to update it according to the force exerted on it by other individuals in the cycle. In the case of an update, a local or global update is selected by a dynamically adjustable probability P s ; otherwise, the individual is retained. Next, we perform combined mutation operations on the updated individuals, so that a new population contains both the reserved and updated individuals for the selection operation. Finally, the fast non-dominated sorting method is adopted on the current population to obtain an optimal Pareto solution set. The parameters’ comparison of MOFECO is given by an experiment and also the performance of MOFECO is compared with three classic evolutionary algorithms Non-dominated Sorting Genetic Algorithm II (NSGA-II), Multi-Objective Particle Swarm Optimization algorithm (MOPSO), Pareto Envelope-based Selection Algorithm II (PESA-II) and two latest algorithms Knee point-driven Evolutionary Algorithm (KnEA) and Non-dominated Sorting and Local Search (NSLS) on solving test function sets Zitzler et al’s Test suite (ZDT), Deb et al’s Test suite (DTLZ), Walking Fish Group (WFG) and Many objective Function (MaF). The experimental results indicate that the proposed MOFECO can approach the true Pareto-optimal front with both better diversity and convergence compared to the five other algorithms.
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