Apoptotic Effects of Anthocyanins from Vitis coignetiae Pulliat Are Enhanced by Augmented Enhancer of the Rudimentary Homolog (ERH) in Human Gastric Carcinoma MKN28 Cells

Evidence suggests that augmented expression of a certain gene can influence the efficacy of targeted and conventional chemotherapies. Here, we tested whether the high expression of enhancer of the rudimentary homolog (ERH), which serves as a prognostic factor in some cancers, can influence the efficacy of anthocyanins isolated from fruits of Vitis coignetiae Pulliat, Meoru in Korea (AIMs) on human gastric cancer cells. The anticancer efficacy of AIMs was augmented in ERH-transfected MKN28 cells (E-MKN28 cells). Molecularly, ERH augmented AIM-induced caspase-dependent apoptosis by activating caspase-3 and -9. The ERH-augmented apoptotic effect was related to mitochondrial depolarization and inhibition of antiapoptotic proteins, XIAP, and Bcl-2. In addition, reactive oxygen species (ROS) generation was augmented in AIMs-treated E-MKN28 cells compared to AIMs-treated naïve MKN28 cells. In conclusion, ERH augmented AIM-induced caspase-dependent mitochondrial-related apoptosis in MKN28 cells. A decrease in expression of Bcl-2 and subsequent excessive ROS generation would be the mechanism for ERH-augmented mitochondrial-related apoptosis in AIMs-treated MKN28 cells. A decrease in expression of XIAP would be another mechanism for ERH-augmented caspase-dependent apoptosis in AIMs-treated MKN28 cells.     

Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo

This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin’s influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.     

A New Tool to Study Parkinsonism in the Context of Aging: MPTP Intoxication in a Natural Model of Multimorbidity

The diurnal rodent Octodon degus (O. degus) is considered an attractive natural model for Alzheimer’s disease and other human age-related features. However, it has not been explored so far if the O. degus could be used as a model to study Parkinson’s disease. To test this idea, 10 adult male O. degus were divided into control group and MPTP-intoxicated animals. Motor condition and cognition were examined. Dopaminergic degeneration was studied in the ventral mesencephalon and in the striatum. Neuroinflammation was also evaluated in the ventral mesencephalon, in the striatum and in the dorsal hippocampus. MPTP animals showed significant alterations in motor activity and in visuospatial memory. Postmortem analysis revealed a significant decrease in the number of dopaminergic neurons in the ventral mesencephalon of MPTP animals, although no differences were found in their striatal terminals. We observed a significant increase in neuroinflammatory responses in the mesencephalon, in the striatum and in the hippocampus of MPTP-intoxicated animals. Additionally, changes in the subcellular expression of the calcium-binding protein S100β were found in the astrocytes in the nigrostriatal pathway. These findings prove for the first time that O. degus are sensitive to MPTP intoxication and, therefore, is a suitable model for experimental Parkinsonism in the context of aging.     

A random key based genetic algorithm for the resource constrained project scheduling problem

This paper presents a genetic algorithm for the Resource Constrained Project Scheduling Problem (RCPSP). The chromosome representation of the problem is based on random keys. The schedule is constructed using a heuristic priority rule in which the priorities of the activities are defined by the genetic algorithm. The heuristic generates parameterized active schedules. The approach was tested on a set of standard problems taken from the literature and compared with other approaches. The computational results validate the effectiveness of the proposed algorithm.     

Three-dimensional analysis of boreholes considering spatial variability of properties and poroelastoplasticity

In general, analysis of oil producing wells is carried out considering that both hydraulic and mechanical parameters of the rock mass are deterministic. Mechanical and hydraulic properties of rock masses and in particular sedimentary rock masses may show a considerable degree of spatial variability. This paper focuses on the evaluation of the three-dimensional borehole response, particularly of the plastic zone, taking into account the spatial variability of both hydraulic and mechanical properties. The analysis is performed with a developed finite element program that incorporates spatial variability, coupled fluid-mechanical effects and elastoplastic behavior of the rock mass. Examples are shown and conclusions are drawn regarding the effect of spatial variability on the three-dimensional borehole analysis.     

Development of a flowsheet for iodine–sulfur thermo-chemical cycle based on optimized Bunsen reaction

Based on the Bunsen reaction process whose operating conditions are optimized to yield an over-azeotropic HI liquid solution, we devised a new flowsheet of iodine–sulfur thermo-chemical cycle. A highly enriched hydrogen-iodide gas can be generated through a series of processes of liquid–liquid separation of product mixture from Bunsen reaction and flash of over-azeotropic HI solution. Operating temperature and pressure for HI enrichment need not to be increased as high as those for existing flowsheets; as a result, the operating conditions become less corrosive. Chance of pipe clogging due to iodine solidification is low because there is no process where iodine is concentrated that high. Enrichment of HI through spontaneous liquid–liquid separation and simple flash processes avoiding complicated separate process is considered to be an additional benefit. Analysis of overall and component material balances showed that excess amount of feed to each process to get a desired output depends on the efficiency of flash and decomposition processes. Compared to previous ones, the proposed flowsheet requires more recirculation flows throughout the whole cycle mainly because only a portion of HI content exceeding the azeotrope is allowed to evaporate in the flash without employing a separate HI enrichment process. Thermal efficiency of the proposed flowsheet was evaluated, together with a series of parametric analyses for the sensitivity to key operating parameters and component performances. It was observed that the thermal efficiency can be raised above 60% at optimal condition.     

The effect of glaze uptake on storage quality of frozen shrimp

Ice-glazing is applied to protect the frozen shrimp from undesirable quality changes during frozen storage. Effects of initial frozen shrimp temperature on glaze uptake; glazing time on glaze uptake; and different glaze percentage on physical and chemical changes of frozen shrimp during storage were investigated. Shrimps were frozen in a spiral freezing machine (?35 °C/15 min); transferred to the air blast freezer until the core temperature reached ?18 °C, ?25 °C and ?30 °C; submitted to glazing process; and stored at ?18 °C for 180 days. The glazing percentage, pH and N-TVB levels were monitored every 45 days. This study has demonstrated the effectiveness of the glazing process as a protecting agent for frozen shrimp. A reasonable range of water uptake could be between 15% and 20% to guarantee the final quality. Therefore, it is important to prevent temperature fluctuations during transportation and storage to maintain the quality of the frozen shrimps.     

The H2-control for jump linear systems: cluster observations of the Markov state

The H₂-norm control problem of discrete-time Markov jump linear systems is addressed in this paper when part of, or the total of the Markov states is not accessible to the controller. The non-observed part of the Markov states is grouped in a number of clusters of observations; the case with a single cluster retrieves the situation when no Markov state is observed. The control action is provided in linear feedback form, which is invariant on each cluster, and this restricted complexity setting is adopted, aiming at computable solutions. We explore a recent result by de Oliveira, Bernussou, and Geromel (Systems Control Lett. 37 (1999) 261) involving an LMI characterization to establish a H₂ solution that is stabilizing in the mean square sense. The novelty of the method is that it can handle in LMI form the situation ranging from no Markov state observation to complete state observation. In addition, when the state observation is complete, the optimal H₂-norm solution is retrieved.     

Chronic HCV hepatitis with normal level of alanine transaminase: interferon therapy of active observation?

AIM: This study of trimetasidine effects on plasmic hemostasis and blood biochemistry in patients with chronic heart failure (CCF) of NYHA functional class II-III. MATERIALS AND METHODS: This study enrolled 30 patients (24 males and 6 females) aged 40-72 years with class II-III CCF, postinfarction cardiosclerosis and ejection fraction under 40%. Previously the patients received perindopril (the inhibitor of angiotensin converting enzyme) in daily dose 2-4 mg, on-demand digoxin and diuretics. Trimetasidine was given in a daily dose 60 mg for 6 months. Before and after the treatment the patients' blood was examined for: levels of factors VII and X of antithrombin III coagulation, soluble fibrinomonomeric complexes (SFMC), fibrinogen, glucose, uric acid, creatinines, total cholesterol, high density lipoprotein, triglycerides, AST, ALT, LDH, acid phosphotase, gamma-GT, sodium, potassium, activated partial thrombin time. RESULTS: Initially, the patients had a 23.9% increase in the levels of factors VII and X, a 14.3% decrease of antithrombin III, 29.8 and 227.6% rise in concentrations of fibrinogen and SFMC, respectively, compared to controls. Aftertreatment values of fibrinogen, factors VII and X, SFMC fell by 21.1, 17 and 35.5%, respectively. The thrombin time arose by 17.9% (p > 0.05). Insignificant inhibition was registered in the activity of acid phosphotase and gamma-GT. Glucose, AST, ALT, LDH levels remained unchanged. Plasma creatinine tended to lowering. Total cholesterol insignificantly increased at high levels of HDL cholesterol (p > 0.05) and reduced levels of triglycerides (p > 0.05). CONCLUSIONS: Trimetasidine therapy, given after conventional treatment with diuretics, digoxin, inhibitor of angiotensin-converting enzyme, aspirin has a beneficial effect in patients with circulatory deficiency through improving hemostatic and biochemical parameters.