Aqueous Extract of Paeonia suffruticosa Inhibits Migration and Metastasis of Renal Cell Carcinoma Cells via Suppressing VEGFR-3 Pathway

Renal cell carcinoma (RCC) cells are characterized by strong drug resistance and high metastatic incidence. In this study, the effects of ten kinds of Chinese herbs on RCC cell migration and proliferation were examined. Aqueous extract of Paeonia suffruticosa (PS-A) exerted strong inhibitory effects on cancer cell migration, mobility, and invasion. The results of mouse xenograft experiments showed that the treatment of PS-A significantly suppressed tumor growth and pulmonary metastasis. We further found that PS-A markedly decreased expression of VEGF receptor-3 (VEGFR-3) and phosphorylation of FAK in RCC cells. Moreover, the activation of Rac-1, a modulator of cytoskeletal dynamics, was remarkably reduced by PS-A. Additionally, PS-A suppressed polymerization of actin filament as demonstrated by confocal microscopy analysis and decreased the ratio of F-actin to G-actin in RCC cells, suggesting that PS-A inhibits RCC cell migration through modulating VEGFR-3/FAK/Rac-1 pathway to disrupt actin filament polymerization. In conclusion, this research elucidates the effects and molecular mechanism for antimigration of PS-A on RCC cells and suggests PS-A to be a therapeutic or adjuvant strategy for the patients with aggressive RCC

Projected Increase of the East Asian Summer Monsoon (Meiyu) in Taiwan by Climate Models With Variable Performance

The active phase of the East Asian summer monsoon (EASM) in Taiwan during May and June, known as Meiyu, produces substantial precipitation for water uses in all sectors of society. Following a companion study that analysed the historical increase in the Meiyu precipitation, the present study conducted model evaluation and diagnosis based on the EASM lifecycle over Taiwan. Higher and lower skill groups were identified from 17 Couple Model Intercomparison Project Phase 5 (CMIP5) models, with five models in each group. Despite the difference in model performance, both groups projected a substantial increase in the Meiyu precipitation over Taiwan. In the higher skill group, weak circulation changes and reduced low‐level convergence point to a synoptically unfavourable condition for precipitation. In the lower skill group, intensified low‐level southwesterly winds associated with a deepened upper level trough enhance moisture pooling. Thus, the projected increase in Meiyu precipitation will likely occur through the combined effects of (1) the extension of a strengthened North Pacific anticyclone enhancing southwesterlies; and (2) more systematically, the Clausius–Clapeyron relationship that increases precipitation intensity in a warmer climate. The overall increase in the Meiyu precipitation projected by climate models of variable performance supports the observed tendency toward more intense rainfall in Taiwan and puts its early June 2017 extreme precipitation events into perspective

Yang-Dan-Tang, Identified from 15 Chinese Herbal Formulae, Inhibits Human Lung Cancer Cell Proliferation via Cell Cycle Arrest

Lung cancer has long been one of the most deadly forms of cancer. The majority of lung cancers are of the non-small-cell lung cancer (NSCLC) type. Here we used the non-small-cell lung carcinoma cell line A549 to screen 15 different traditional Chinese herbal medicine (CHM) formulae to explore the possible mechanisms of alternative medicine in lung cancer therapy. We identified three formulae (Formulae 3, 5, and 14) that substantially decreased the survival of A549 cells but did not affect MRC5 normal lung tissue cells. Formula 14, Yang-Dan-Tang, a modified decoction of Ramulus Cinnamomi Cassiae, was chosen for further characterization. Flow cytometry analysis showed that treatment of Formula 14 induced cell cycle arrest in G1 and G2 phase without causing significant cell death. These results were also confirmed by Western blot analysis, with decreased expression of G1/S and G2/M promoting cell cycle machinery including cyclin D3, cyclin B1, CDK4, and CDK6. This study provides further insight into the possible working mechanism of Yang-Dan-Tang in patients

Tsengwen Reservoir Watershed Hydrological Flood Simulation Under Global Climate Change Using the 20 km Mesh Meteorological Research Institute Atmospheric General Circulation Model (MRI-AGCM)

Severe rainstorms have occurred more frequently in Taiwan over the last decade. To understand the flood characteristics of a local region under climate change, a hydrological model simulation was conducted for the Tsengwen Reservoir watershed. The model employed was the Integrated Flood Analysis System (IFAS), which has a conceptual, distributed rainfall-runoff analysis module and a GIS data-input function. The high-resolution rainfall data for flood simulation was categorized into three terms: 1979 - 2003 (Present), 2015 - 2039 (Near-future), and 2075 - 2099 (Future), provided by the Meteorological Research Institute atmospheric general circulation model (MRI-AGCM). Ten extreme rainfall (top ten) events were selected for each term in descending order of total precipitation volume. Due to the small watershed area the MRI-AGCM3.2S data was downsized into higher resolution data using the Weather Research and Forecasting Model. The simulated discharges revealed that most of the Near-future and Future peaks caused by extreme rainfall increased compared to the Present peak. These ratios were 0.8 - 1.6 (Near-future/Present) and 0.9 - 2.2 (Future/Present), respectively. Additionally, we evaluated how these future discharges would affect the reservoir¡¦s flood control capacity, specifically the excess water volume required to be stored while maintaining dam releases up to the dam¡¦s spillway capacity or the discharge peak design for flood prevention. The results for the top ten events show that the excess water for the Future term exceeded the reservoir¡¦s flood control capacity and was approximately 79.6 - 87.5% of the total reservoir maximum capacity for the discharge peak design scenario

Isolation, Culture and Characterization of Hirsutella sinensis Mycelium from Caterpillar Fungus Fruiting Body

The caterpillar fungus Ophiocordyceps sinensis (previously called Cordyceps sinensis) has been used for centuries in Asia as a tonic to improve health and longevity. Recent studies show that O. sinensis produces a wide range of biological effects on cells, laboratory animals and humans, including anti-fatigue, anti-infection, anti-inflammatory, antioxidant, and anti-tumor activities. In view of the rarity of O. sinensis fruiting bodies in nature, cultivation of its anamorph mycelium represents a useful alternative for large-scale production. However, O. sinensis fruiting bodies harvested in nature harbor several fungal contaminants, a phenomenon that led to the isolation and characterization of a large number of incorrect mycelium strains. We report here the isolation of a mycelium from a fruiting body of O. sinensis and we identify the isolate as O. sinensis’ anamorph (also called Hirsutella sinensis) based on multi-locus sequence typing of several fungal genes (ITS, nrSSU, nrLSU, RPB1, RPB2, MCM7, β-tubulin, TEF-1α, and ATP6). The main characteristics of the isolated mycelium, including its optimal growth at low temperature (16°C) and its biochemical composition, are similar to that of O. sinensis fruiting bodies, indicating that the mycelium strain characterized here may be used as a substitute for the rare and expensive O. sinensis fruiting bodies found in nature

Isotretinoin Oil-Based Capsule Formulation Optimization

The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (X1), hydrogenated coconut oil (X2), and soybean oil (X3). The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM). Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (X1X2, X1X3, and X2X3) showed more potential influence than that of the main factors (X1, X2, and X3). An optimal predicted formulation with Y10 min, Y30 min, Y60 min, and Y90 min release values of 12.3%, 36.7%, 73.6%, and 92.7% at X1, X2, and X3 of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor f2 was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile

Frailty and Its Impact on Health-Related Quality of Life: A Cross-Sectional Study on Elder Community-Dwelling Preventive Health Service Users

BACKGROUND: The purpose of this study was to identify the incidence of frailty and to investigate the relationship between frailty status and health-related quality of life (HRQoL) in the community-dwelling elderly population who utilize preventive health services. METHODS: People aged 65 years and older who visited a medical center in Taipei City from March to August in 2011 for an annual routine check-up provided by the National Health Insurance were eligible. A total of 374 eligible elderly adults without cognitive impairment had a mean age of 74.6±6.3 years. Frailty status was determined according to the Fried frailty criteria. HRQoL was measured with Short Form-36 (SF-36). Multiple regression analyses examined the relationship between frailty status and the two summary scales of SF-36. Models were adjusted for the participants' sociodemographic and health status. RESULTS: After adjusting for sociodemographic and health-related covariables, frailty was found to be more significantly associated (p<0.001) with lower scores on both physical and mental health-related quality of life summary scales compared with robustness. For the frailty phenotypes, slowness represented the major contributing factor in the physical component scale of SF-36, and exhaustion was the primary contributing factor in the mental component scale. CONCLUSION: The status of frailty is closely associated with HRQoL in elderly Taiwanese preventive health service users. The impacts of frailty phenotypes on physical and mental aspects of HRQoL differ

Role of the CCAAT-Binding Protein NFY in SCA17 Pathogenesis

Spinocerebellar ataxia 17 (SCA17) is caused by expansion of the polyglutamine (polyQ) tract in human TATA-box binding protein (TBP) that is ubiquitously expressed in both central nervous system and peripheral tissues. The spectrum of SCA17 clinical presentation is broad. The precise pathogenic mechanism in SCA17 remains unclear. Previously proteomics study using a cellular model of SCA17 has revealed reduced expression of heat shock 70 kDa protein 5 (HSPA5) and heat shock 70 kDa protein 8 (HSPA8), suggesting that impaired protein folding may contribute to the cell dysfunction of SCA17 (Lee et al., 2009). In lymphoblastoid cells, HSPA5 and HSPA8 expression levels in cells with mutant TBP were also significantly lower than that of the control cells (Chen et al., 2010). As nuclear transcription factor Y (NFY) has been reported to regulate HSPA5 transcription, we focused on if NFY activity and HSPA5 expression in SCA17 cells are altered. Here, we show that TBP interacts with NFY subunit A (NFYA) in HEK-293 cells and NFYA incorporated into mutant TBP aggregates. In both HEK-293 and SH-SY5Y cells expressing TBP/Q61∼79, the level of soluble NFYA was significantly reduced. In vitro binding assay revealed that the interaction between TBP and NFYA is direct. HSPA5 luciferase reporter assay and endogenous HSPA5 expression analysis in NFYA cDNA and siRNA transfection cells further clarified the important role of NFYA in regulating HSPA5 transcription. In SCA17 cells, HSPA5 promoter activity was activated as a compensatory response before aggregate formation. NFYA dysfunction was indicated in SCA17 cells as HSPA5 promoter activity reduced along with TBP aggregate formation. Because essential roles of HSPA5 in protection from neuronal apoptosis have been shown in a mouse model, NFYA could be a target of mutant TBP in SCA17