Chlorella sorokiniana induces mitochondrial-mediated apoptosis in human non-small cell lung cancer cells and inhibits xenograft tumor growth in vivo.

BACKGROUND: Lung cancer is one of the leading causes of cancer related deaths worldwide. Marine microalgae are a source of biologically active compounds and are widely consumed as a nutritional supplement in East Asian countries. It has been reported that Chlorella or Chlorella extracts have various beneficial pharmacological compounds that modulate immune responses; however, no studies have investigated the anti-cancer effects of Chlorella sorokiniana (CS) on non-small cell lung cancer (NSCLC). METHODS: In this study, we evaluated the anti-cancer effects of CS in two human NSCLC cell lines (A549 and CL1-5 human lung adenocarcinoma cells), and its effects on tumor growth in a subcutaneous xenograft tumor model. We also investigated the possible molecular mechanisms governing the pharmacological function of CS. RESULTS: Our results showed that exposure of the two cell lines to CS resulted in a concentration-dependent reduction in cell viability. In addition, the percentage of apoptotic cells increased in a dose-dependent manner, suggesting that CS might induce apoptosis in human NSCLC cells. Western blot analysis revealed that exposure to CS resulted in increased protein expression of the cleaved/activated forms of caspase-3, caspase-9, and PARP, except caspase-8. ZDEVD (caspase-3 inhibitor) and Z-LEHD (caspase-9 inhibitor) were sufficient at preventing apoptosis in both A549 and CL1-5 cells, proving that CS induced cell death via the mitochondria-mediated apoptotic pathway. Exposure of A549 and CL1-5 cells to CS for 24 h resulted in decreased expression of Bcl-2 protein and increased expression of Bax protein as well as decreased expression of two IAP family proteins, survivin and XIAP. CONCLUSIONS: We demonstrated that CS induces mitochondrial-mediated apoptosis in NSCLC cells via downregulation of Bcl-2, XIAP and survivin. In addition, we also found that the tumors growth of subcutaneous xenograft in vivo was markedly inhibited after oral intake of CS.

Characterization of volatile organic compounds in the vicinity of an optoelectronics industrial park in Taiwan.

This study aimed to determine the concentration of volatile organic compounds (VOCs) and investigate the impacts of traffic and industrial activities on the concentration of VOCs near the Central Taiwan Science Park (CTSP) in Taiwan during 2005. Twelve-hour canister sampling was performed at 10 sites near CTSP every season. Samples were analyzed by gas chromatography with a mass-selective detector. The traffic flow rate, industrial production rates, and meteorological information were also collected to assess their impacts on VOC concentrations using multiple linear regression models. The major components determined in the atmosphere were toluene (29.4-218.8 microg m(-3)), acetone (30-71.3 microg m(-3)), m/p-xylene (7.8-51.7 microg m(-3)), and ethanol (16.4-47.8 microg m(-3)); only ethanol revealed a pattern of increasing concentration from spring to winter. The log-transformed mean concentrations of toluene, acetone, and ethanol were significantly associated with the production rates of the optoelectronic companies after adjustment for traffic flow and meteorological factors (P < 0.05). There was no significant association between the total traffic flow rate and any log-transformed mean concentrations of VOCs. Each $1 million (U.S.) increase in optoelectronic sales was significantly associated with increasing mean concentrations of 1.29 +/- 1.08 microg m(-3) for toluene, 1.13 +/- 1.05 microg m(-3) for acetone, and 1.25 +/- 1.09 microg m(-3) for ethanol. The authors' findings suggest that optoelectronic industrial activities are still the predominant source for VOC emissions surrounding this industrial park.

Survival rate variation among different types of hospitalized traumatic cardiac arrest: A retrospective and nationwide study.

Studies regarding the prognostic factors for survival conditions and the proportions of survival to discharge among different types of hospitalized traumatic cardiac arrest (TCA) during the period of postresuscitation are limited.This nationwide study was designed to determine certain parameters and clarify the effect of various injuries on the survival of hospitalized TCA patients to discharge.Data were retrieved from the National Health Insurance Research Database (NHIRD) from 2007 to 2013 in Taiwan. We reviewed patients with a diagnosis of TCA using International Classification of Disease Clinical Modification, 9th revision codes (ICD-9-CM codes). Patients identified for analysis were simultaneously coded in traumatic etiology (ICD-9-CM codes: 800-999) and cardiac arrest (ICD-9-CM codes: 427.41 or 427.5). The determinants and effects of different types of injury on survival were evaluated by SPSS 22.0 (IBM, Armonk, NY).A total of 3481 cases of hospitalized TCA were selected from the NHIRD. The overall rate of survival to discharge was 22.1%. The results indicated a decreased adjusted odds ratio (aOR) of survival to discharge with higher numbers of organ failure (aOR: 0.82; 95% confidence interval [CI]: 0.73-0.92). Patients with ventricular fibrillation had a better discharge rate (aOR: 4.33; 95% CI: 3.29-5.70). Two parameters, transfer to another hospital and the number of intensive care unit beds, were positively correlated with survival. Compared with traffic accidents, different injuries associated with survival to discharge were identified; the aOR (95% CI) was 1.89 (1.12-3.19) for poisoning, 1.63 (1.13-2.36) for falls, and 2.00 (1.36-2.92) for drowning/suffocation.This study has shown that hospitalized TCA patients with multiple organ failure may be less likely to be discharged from the hospital. The presence of ventricular fibrillation rhythm on admission increased the odds of survival to discharge. In the phase of postcardiac arrest care, the number of intensive care unit beds and transfer to another hospital were positively correlated with survival. Those events attributed to traffic accidents have a much worse influence on the main outcome.

Estimation of students' exposure to metal concentrations from river-dust episodes during 1994-2012.

Two elementary schools (Shiuguang and Fongrong) from Yulin County in Taiwan, near a main area of potential exposure to Aeolian river-dust, were selected to collect outdoor and indoor PM10 aerosols and to measure five metals in PM10 (As, Ni, Cr, Cd, and Mn). Significant relationships (p < 0.01) were found between outdoor PM10 concentrations at Lunbei's air quality monitoring station and the two elementary schools. The outdoor PM10 concentrations at the monitoring station and the schools' indoor PM10 concentrations also showed significant correlations. This study also established a relationship between the outdoor and indoor concentrations of PM10 and metals in the schools. Estimations were made regarding students' 8 h of exposure to metal concentrations from river-dust episodes during 1994-2012, based on correlation equations that were shown to be statistically significant.

Hericium erinaceus Inhibits TNF-α-Induced Angiogenesis and ROS Generation through Suppression of MMP-9/NF-κB Signaling and Activation of Nrf2-Mediated Antioxidant Genes in Human EA.hy926 Endothelial Cells.

Hericium erinaceus (HE) is an edible mushroom that has been shown to exhibit anticancer and anti-inflammatory activities. We investigated the antiangiogenic and antioxidant potentials of ethanol extracts of HE in human endothelial (EA.hy926) cells upon tumor necrosis factor-α- (TNF-α-) stimulation (10 ng/mL). The underlying molecular mechanisms behind the pharmacological efficacies were elucidated. We found that noncytotoxic concentrations of HE (50-200 µg/mL) significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation of endothelial cells. HE treatment suppressed TNF-α-induced activity and/or overexpression of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, HE downregulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) followed by suppression of I-κB (inhibitor-κB) degradation. Data from fluorescence microscopy illustrated that increased intracellular ROS production upon TNF-α-stimulation was remarkably inhibited by HE pretreatment in a dose-dependent manner. Notably, HE triggered antioxidant gene expressions of heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase (γ-GCLC), and glutathione levels, which may contribute to inhibition of ROS. Increased antioxidant status was associated with upregulated nuclear translocation and transcriptional activation of NF-E2 related factor-2 (Nrf2) in HE treated cells. Our findings conclude that antiangiogenic and anti-inflammatory activities of H. erinaceus may contribute to its anticancer property through modulation of MMP-9/NF-κB and Nrf2-antioxidant signaling pathways.

Screening procedure for airborne pollutants emitted from a high-tech industrial complex in Taiwan.

Despite the modernization of computational techniques, atmospheric dispersion modeling remains a complicated task as it involves the use of large amounts of interrelated data with wide variability. The continuously growing list of regulated air pollutants also increases the difficulty of this task. To address these challenges, this study aimed to develop a screening procedure for a long-term exposure scenario by generating a site-specific lookup table of hourly averaged dispersion factors (χ/Q), which could be evaluated by downwind distance, direction, and effective plume height only. To allow for such simplification, the average plume rise was weighted with the frequency distribution of meteorological data so that the prediction of χ/Q could be decoupled from the meteorological data. To illustrate this procedure, 20 receptors around a high-tech complex in Taiwan were selected. Five consecutive years of hourly meteorological data were acquired to generate a lookup table of χ/Q, as well as two regression formulas of plume rise as functions of downwind distance, buoyancy flux, and stack height. To calculate the concentrations for the selected receptors, a six-step Excel algorithm was programmed with four years of emission records and 10 most critical toxics were screened out. A validation check using Industrial Source Complex (ISC3) model with the same meteorological and emission data showed an acceptable overestimate of 6.7% in the average concentration of 10 nearby receptors. The procedure proposed in this study allows practical and focused emission management for a large industrial complex and can therefore be integrated into an air quality decision-making system.

Antrodia salmonea in submerged culture exhibits antioxidant activities in vitro and protects human erythrocytes and low-density lipoproteins from oxidative modification.

Antrodia salmonea is well known in Taiwan as a beneficial mushroom. In the present study, we investigated the antioxidant activity of whole fermented broth (AS), filtrate (ASF), and mycelia (ASM) of A. salmonea using different antioxidant models. Furthermore, the effect of A. salmonea on AAPH-induced oxidative hemolysis of human erythrocytes and CuSO4-induced oxidative modification of human low-density lipoproteins (LDLs) was examined. We found that the AS, ASF, and ASM possess effective antioxidant activity against various oxidative systems including superoxide anion scavenging, reducing power, metal chelation, and DPPH radical scavenging. Further, AAPH-induced oxidative hemolysis in erythrocytes was prevented by AS, ASF, and ASM. Notably, AS, ASF, and ASM appear to possess powerful antioxidant activities against CuSO4-induced oxidative modification of LDL as assessed by malondialdehyde (MDA) formation, cholesterol degradation, and the relative electrophoretic mobility of oxidized LDL. It is noteworthy that AS had comparatively strong antioxidant ability compared to ASF or ASM, which is well correlated with the content of their total polyphenols. Thus, A. salmonea may exert antioxidant properties and offer protection from atherogenesis.

Evaluation of the vehicle contributions of metals to indoor environments.

A large number of diesel vehicles carrying gravel and sand shuttle back and forth every day on the major thoroughfares (Tai-16 and Tai-21) from Shinyi to Jiji in Nantou, Taiwan. A total of 10 stations along the major thoroughfares were selected as the exposure sites, whereas a small village located ∼9 km from a main traffic route was selected as the control site. Outdoor and indoor aerosol samples were collected using high-volume samplers and Harvard samplers, respectively. The metal concentrations of outdoor and indoor PM(10) at the exposure sites were, respectively, higher than those at the control site. The plots between metal contents in the aerosols and road dust showed that diesel vehicles contributed significant amounts of metals to the outdoor and indoor aerosols at the exposure sites. Household dust samples along the roadside within 30 m of the main road in the small towns were collected using the wipe method. Based on the results of principal component analysis (PCA), three major components for household dust were identified: resuspended from road dust, brake wear and diesel emissions. Enrichment factors were applied to assess the contribution of pollution sources to household dust. These factors were calculated with respect to unpolluted river dust samples (EF(river)) and road dust (EF(road)). The differences between EF(river) and EF(road) could be mainly attributed to the effects of resuspension by passing vehicles. Approximately 72%, 68%, 68%, 73% and 86% of the vehicle-related metals Pb, Zn, Cu, Ni and Mo content, respectively, in household dust were the result of the resuspension of road dust by passing vehicles. The data of daily intakes of five metals (i.e., Fe, Pb, Cu, Ni and Mo) from inhalation and ingestion pathways showed that the doses from the ingestion pathway were much higher than those from the inhalation pathway.

Computational analysis of novel drugs designed for use as acetylcholinesterase inhibitors and histamine H3 receptor antagonists for Alzheimer's disease by docking, scoring and de novo evolution.

Alzheimer's disease (AD) was first described by Alois Alzheimer in 1907. AD is the most prevalent dementia- related disease, affecting over 20 million individuals worldwide. Currently, however, only a handful of drugs are available and they are at best only able to offer some relief of symptoms. Acetylcholinesterase (AChE) inhibitors, antioxidants, metal chelators, monoamine oxidase inhibitors, anti-inflammatory drugs and NMDA inhibitors are usually used to attempt to cure this disease. AChE inhibitors are the most effective therapy for AD at present. Researchers have found that histamine H3 receptor antagonists decrease re-uptake of acetylcholine and the nervous transmitter substance acetylcholine increases. In this study, we designed compounds by using docking, de novo evolution and adsorption, distribution, metabolism, excretion and toxicity (ADMET) analysis to AChE inhibitors as well as histamine H3 receptor antagonists to forward drug research and investigate the potent compounds which can pass through the blood-brain barrier. The novel drugs may be useful for the treatment of AD, based on the results of this theoretical calculation study. We will subsequently examine them in future experiments.

Anti-metastatic activities of Antrodia camphorata against human breast cancer cells mediated through suppression of the MAPK signaling pathway.

The fermented culture broth of Antrodia camphorata (A. camphorata) has been shown to promote cell cycle arrest and apoptosis of human estrogen-nonresponsive MDA-MB-231 cells. Herein, we demonstrate that non-cytotoxic concentrations (20-80 µg/mL) of A. camphorata markedly inhibited the invasion/migration of highly metastatic MDA-MB-231 cells as shown by an in vitro transwell and a wound-healing repair assay. The results of a gelatin zymography assay showed that A. camphorata suppressed the activity of matrix metalloproteinase (MMP)-9 and urokinase plasminogen activator (uPA). Western blot results demonstrated that treatment with A. camphorata decreased the expression of MMP-9, MMP-2, uPA, uPA receptor (uPAR) and vascular endothelial growth factor (VEGF); while the expression of the endogenous inhibitors of these proteins, i.e., tissue inhibitors of MMP (TIMP-1 and TIMP-2), and plasminogen activator inhibitor (PAI)-1, increased. Further investigation revealed that A. camphorata suppressed the phosphorylation of ERK1/2, p38, and JNK1/2. A. camphorata treatment also led to a dose-dependent inhibition on NF-κB binding and activation. This is the first report confirming the anti-metastatic activity of this potentially beneficial mushroom against human breast cancer.

Exploring the background features of acidic and basic air pollutants around an industrial complex using data mining approach.

Air pollution data around a monitored site are normally difficult to analyze due to highly inter-related meteorological and topographical factors on top of many complicated atmospheric chemical interactions occurred in local and regional wind fields. The challenge prompts this study to develop a comprehensive data-mining algorithm of cluster analysis followed by meteorological and interspecies correlations to mitigate the inherent data complexity and dissimilarity. This study investigated the background features of acidic and basic air pollutants around a high-tech industrial park in Taiwan. Monthly samplings were taken at 10 sites around the park in a year. The temporal distribution plots show a baseline with two characteristic groups of high and low peaks. Hierarchical cluster analysis confirms that high peaks were primarily associated with low speed south wind in summer for all the chemical species, except for F(-), Cl(-), NH(3) and HF. Crosschecking with the topographical map identifies several major external sources in south and southwest. Further meteorological correlation suggests that HCl is highly positively associated with humidity, while Cl(-) is highly negatively associated with temperature, both for most stations. Interestingly, HNO(3) is highly negatively associated with wind speed for most stations and the hotspot was found in summer and around the foothill of Da-Tu Mountain in the northwest, a stagnant pocket on the study site. However, F(-) is highly positively associated with wind speed at downwind stations to the prevailing north wind in winter, indicating an internal source from the north. The presence of NH(4)(+) stimulates the formation of NO(3)(-), SO(4)(-2) (R=0.7), and HNO(3), H(2)SO(4), NH(3) (R=0.3-0.4). As H(2)SO(4) could be elevated to a level as high as 40% of the regulated standard, species interactions may be a dominate mechanism responsible for the substantial increase in summer from external sources.

A comparison of swine wastewater treatment using real-time and fixed-time two-stage sequencing batch reactors.

This study compared the swine wastewater treatment of two identical lab-scale two-stage sequencing batch reactors (TSSBR) under similar conditions except that one was operated on a fixed-time mode and the other on a real-time mode. While both TSSBR systems performed very well, the real-time TSSBR performed far better then the fixed-time TSSBR, in every aspect of carbon, nitrogen, and phosphorous removal. The removals of COD, TOC, were at 97% and for BOD5 even at 99.7%. In terms of NH4-N and TKN removals, the real-time TSSBR achieved removal of over 98%. For phosphorus removals (Ortho-P and total P) the results from the real-time TSSBR was quite remarkable at 97.7%.

Disinfection of hospital wastewater by continuous ozonization.

The disinfection of hospital wastewaters using the ozonization process was studied. The concentrations of ozone required to reach a sudden drop of coliform and Pseudomonas aeruginosa in the wastewater are 4.0-7.0 and 3.0-5.0 mg L(-1), respectively. For the hospital wastewater, the disinfection efficiencies were 0.518S(-1.1) for coliforms, 0.509S(-1.06) for Pseudomonas aeruginosa and 0.254S-(1.54) for total count, respectively. As to the effects of ozone input methods on the disinfection efficiency, the continuous ozonization process was ten times higher than the batch input process. The low COD removal rate was obtained at 25.0 mgL(-1) of ozone concentration for hospital wastewater. However, more biodegradable compounds resulted in the treated mixture.