Ethanol extract of Dunaliella salina induces cell cycle arrest and apoptosis in A549 human non-small cell lung cancer cells

[[abstract]]The ethanol extract of Dunaliella salina (EDS) on proliferation and apoptosis in the A549 human lung cancer cell line and their associated protein expressions were investigated. After 24 and 48 h treatment, MTT assay showed that 25 mu g/ml of EDS significantly reduced A549 cell proliferation by 25.2% (p<0.05) and 48.3% (p<0.01), respectively. To explore its molecular mechanisms in regulating cell proliferation, we first showed that EDS markedly reduced A549 proliferation via inhibition of BrdU incorporation at 25 mu g/ml by 65.8% (p<0.001). By cytometric analysis, EDS was found to induce apoptosis and cell cycle arrest in the G0/G1 phase. In the DNA gel electrophoresis assay, EDS (25, 50 and 100 mu g/ml) induced significant apoptosis at 48 h. Annexin V/Propodium iodide double staining demonstrated that administration of EDS (25 mu g/ml) in 12, 24 and 48 h induces apoptosis of 27.7%, 30.7%, and 38.7%. Western blotting assay demonstrated that EDS significantly increased the expression of cyclin-dependent kinase (CDK) inhibitors p53 and p21 and death-receptor proteins Fas and FasL. Bax expression was also elevated by treatment with EDS. Our data suggested that EDS could influence the antiproliferative effects and induce cell cycle G0/G1 arrest and apoptosis of A549 lung cancer cells

Therapeutic Applications and Mechanisms of YC-1: A Soluble Guanylate Cyclase Stimulator

Nitric oxide (NO) is an essential endogenous vasodilator to maintain vascular homeostasis, whose effects are mainly mediated by NO-dependent soluble guanylate cyclase (sGC) which catalyzes the synthesis of cyclic guanosine monophosphate (cGMP), a critical mediator of vascular relaxation. YC-1, a novel NO-independent sGC stimulator, was first introduced as an inhibitor of platelet aggregation and thrombosis. Accumulating studies revealed that YC-1 has multiple medication potentials to use for a broad spectrum of diseases ranging from cardiovascular diseases to cancers. In contrast to NO donors, YC-1 has a more favorable safety profile and low medication tolerance. In this chapter, we introduce canonical and pathological roles of NO, review activations, and regulatory mechanisms of YC-1 on NO-independent sGC/cGMP pathway and present the potential pharmacological applications and molecular mechanisms of YC-1

Bioactive Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

Four new eunicellin-based diterpenoids, krempfielins A–D (1–4), along with two known compounds (5 and 6) have been isolated from a soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compounds 5 and 6 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 2, 3, 5 and 6 were shown to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells

Hispolon Protects against Acute Liver Damage in the Rat by Inhibiting Lipid Peroxidation, Proinflammatory Cytokine, and Oxidative Stress and Downregulating the Expressions of iNOS, COX-2, and MMP-9

The hepatoprotective potential of hispolon against carbon tetrachloride (CCl4)-induced liver damage was evaluated in preventive models in rats. Male rats were intraperitoneally treated with hispolon or silymarin once daily for 7 consecutive days. One hour after the final hispolon or silymarin treatment, the rats were injected with CCl4. Administration with hispolon or silymarin significantly decreased the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum and increased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione (GSH) content and decreased the malondialdehyde (MDA) content in liver compared with CCl4-treated group. Liver histopathology also showed that hispolon reduced the incidence of liver lesions induced by CCl4. In addition, hispolon decreased nitric oxide (NO) production and tumor necrosis factor (TNF-α), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) activation in CCl4-treated rats. We also examined the involvement of matrix metalloproteinase (MMP)-9 in the development of CCl4-induced liver damage in rats. Hispolon inhibited the expression of MMP-9 protein, indicating that MMP-9 played an important role in the development of CCl4-induced rat liver damage. Therefore, we speculate that hispolon protects rats from liver damage through their prophylactic redox balancing ability and anti-inflammation capacity

Analgesic Effects and the Mechanisms of Anti-Inflammation of Hispolon in Mice

Hispolon, an active ingredient in the fungi Phellinus linteus was evaluated with analgesic and anti-inflammatory effects. Treatment of male ICR mice with hispolon (10 and 20 mg/kg) significantly inhibited the numbers of acetic acid-induced writhing response. Also, our result showed that hispolon (20 mg/kg) significantly inhibited the formalin-induced pain in the later phase (P<.01). In the anti-inflammatory test, hispolon (20 mg/kg) decreased the paw edema at the fourth and fifth hour after λ-carrageenin (Carr) administration, and increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) in the liver tissue. We also demonstrated that hispolon significantly attenuated the malondialdehyde (MDA) level in the edema paw at the fifth hour after Carr injection. Hispolon (10 and 20 mg/kg) decreased the nitric oxide (NO) levels on both the edema paw and serum level at the fifth hour after Carr injection. Also, hispolon (10 and 20 mg/kg) diminished the serum TNF-α at the fifth hour after Carr injection. The anti-inflammatory mechanisms of hispolon might be related to the decrease in the level of MDA in the edema paw by increasing the activities of SOD, GPx and GRx in the liver. It probably exerts anti-inflammatory effects through the suppression of TNF-α and NO

Antinociceptive Activities and the Mechanisms of Anti-Inflammation of Asiatic Acid in Mice

Asiatic acid (AA), a pentacyclic triterpene compound in the medicinal plant Centella asiatica, was evaluated for antinociceptive and anti-inflammatory effects. Treatment of male ICR mice with AA significantly inhibited the numbers of acetic acid-induced writhing responses and the formalin-induced pain in the late phase. In the anti-inflammatory test, AA decreased the paw edema at the 4th and 5th h after λ-carrageenan (Carr) administration and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue. AA decreased the nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels on serum level at the 5th h after Carr injection. Western blotting revealed that AA decreased Carr-induced inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and nuclear factor-κB (NF-κB) expressions at the 5th h in the edema paw. An intraperitoneal (i.p.) injection treatment with AA also diminished neutrophil infiltration into sites of inflammation as did indomethacin (Indo). The anti-inflammatory mechanisms of AA might be related to the decrease in the level of MDA, iNOS, COX-2, and NF-κB in the edema paw via increasing the activities of CAT, SOD, and GPx in the liver

Sustainabilitas Arsitektur Masjid: Evaluasi Konsep “Simple Architecture” sebagai Implementasi Desain Arsitektur Berkelanjutan suatu Kawasan

Makalah ini membahas aspek-aspek “kesederhanaan” (simplicity) sebagai konsep desain bangunan masjid secara berkelanjutan (sustainable) sesuai konteks dengan mengambil studi kasus masjid kawasan Al-Irsyad Satya Kota Baru Parahyangan, Bandung. Masjid sebagai subyek arsitektur dan pusat ibadah menjadi ruang publik yang didesain dari elemen-elemen yang secara ideal mengandung nilai-nilai Islam dan bertujuan mendukung fungsinya. Desain masjid berkonsep simple atau “sederhana” digunakan sebagai alternatif kontemporer untuk mengoptimalisasi fungsi tersebut, meliputi struktur bangunan hingga biaya pemeliharaan (maintenance) sesuai prinsip keberlanjutan. Keterkaitan erat bangunan masjid dengan aktivitas masyarakat berpotensi melibatkan partisipasi masyarakat dan pengelola dalam menerapkan program sustainabilitas sesuai konteks lingkungannya. Metode yang digunakan dalam penelitian ini berbasis pendekatan Grounded Theory secara kualitatif melalui pengumpulan data dari kegiatan observasi, interview dan analisis program keberlanjutan kawasan. Penelitian menemukan keterkaitan konsep “sederhana” yang mendukung sustainabilitas desain sekaligus menggarisbawahi evaluasi konsep desain “sederhana” yang hadir serta faktor pemeliharaan/pengembangan masjid dan kawasan

An Overview of Regional Experiments on Biomass Burning Aerosols and Related Pollutants in Southeast Asia: From BASE-ASIA and the Dongsha Experiment to 7-SEAS

By modulating the Earth-atmosphere energy, hydrological and biogeochemical cycles, and affecting regional-to-global weather and climate, biomass burning is recognized as one of the major factors affecting the global carbon cycle. However, few comprehensive and wide-ranging experiments have been conducted to characterize biomass-burning pollutants in Southeast Asia (SEA) or assess their regional impact on meteorology, the hydrological cycle, the radiative budget, or climate change. Recently, BASEASIA (Biomass-burning Aerosols in South-East Asia: Smoke Impact Assessment) and the 7-SEAS (7- South-East Asian Studies) Dongsha Experiment were conducted during the spring seasons of 2006 and 2010 in northern SEA, respectively, to characterize the chemical, physical, and radiative properties of biomass-burning emissions near the source regions, and assess their effects. This paper provides an overview of results from these two campaigns and related studies collected in this special issue, entitled Observation, modeling and impact studies of biomass burning and pollution in the SE Asian Environment. This volume includes 28 papers, which provide a synopsis of the experiments, regional weatherclimate, chemical characterization of biomass-burning aerosols and related pollutants in source and sink regions, the spatial distribution of air toxics (atmospheric mercury and dioxins) in source and remote areas, a characterization of aerosol physical, optical, and radiative properties, as well as modeling and impact studies. These studies, taken together, provide the first relatively complete dataset of aerosol chemistry and physical observations conducted in the sourcesink region in the northern SEA, with particular emphasis on the marine boundary layer and lower free troposphere (LFT). The data, analysis and modeling included in these papers advance our present knowledge of source characterization of biomass-burning pollutants near the source regions as well as the physical and chemical processes along transport pathways. In addition, we raise key questions to be addressed by a coming deployment during springtime 2013 in northern SEA, named 7-SEASBASELInE (Biomass-burning Aerosols Stratocumulus Environment: Lifecycles and Interactions Experiment). This campaign will include a synergistic approach for further exploring many key atmospheric processes (e.g., complex aerosol-cloud interactions) and impacts of biomass burning on the surface-atmosphere energy budgets during the lifecycles of biomass burning emissions

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P &lt; 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms