Chih-Wei Chou

Ellagic acid protects human keratinocyte (HaCaT) cells against UVA-induced oxidative stress and apoptosis through the upregulation of the HO-1 and Nrf-2 antioxidant genes.

UV radiation from the sun is a potent environmental risk factor in the pathogenesis of skin damage. Much of the skin damage caused by ultraviolet A (UVA) irradiation from the sun is associated with oxidative stress. The aim of this study was to investigate the protective role of ellagic acid (25-75 μM), a natural antioxidant, against UVA (5-20 J/cm(2))-induced oxidative stress and apoptosis in human keratinocyte (HaCaT) cells and to reveal the possible mechanisms underlying this protective efficacy. Ellagic acid pre-treatment markedly increased HaCaT cell viability and suppressed UVA-induced ROS generation and MDA formation. Moreover, ellagic acid pre-treatment prevented UVA-induced DNA damage as evaluated by the comet assay. Ellagic acid treatment also significantly inhibited the UVA-induced apoptosis of HaCaT cells, as measured by a reduction of DNA fragmentation, mitochondria dysfunction, ER stress, caspase-3 activation, and Bcl-2/Bax deregulation. Notably, the antioxidant potential of ellagic acid was directly correlated with the increased expression of HO-1 and SOD, which was followed by the downregulation of Keap1 and the augmented nuclear translocation and transcriptional activation of Nrf2 with or without UVA irradiation. Nrf2 knockdown diminished the protective effects of ellagic acid. Therefore, ellagic acid may be useful for the treatment of UVA-induced skin damage.

Effects of additives on the photo-induced grafting polymerization of N-isopropylacrylamide gel onto PET film and PP nonwoven fabric surface

Abstract In this study, the thermosensitive gels were grafted onto plasma-activated polyethylene terephthalate (PET) film and polypropylene (PP) nonwoven fabric surface. The Ar* plasma pretreatment was carried out and subsequent photo-induced surface graft polymerization was employed to graft the N-isopropylacrylamide (NIPAAm). The effects of additives during the grafting were accessed. The additives used were ammonium peroxodisulfate (APS, initiator), N,N,N′,N′-tetra-methylethylene-diamine (TEMED, promoter) and N,N′-methylenebisacrylamide (NMBA, cross-linking agent). The results indicate that the additives of APS, TEMED and NMBA will be beneficial in promoting the grafting. The additives, including all three, will give the best result. These grafted gels exhibit a lower critical solution temperature (LCST) at about 32 °C, which shows that the temperature-responsive behavior of bulk P (NIPAAm) hydrogel was preserved.

Synthesis of antibacterial TiO2/PLGA composite biofilms

UNLABELLED This study developed a TiO2/PLGA [poly(lactic-co-glycolic acid)] composite biomaterial, which possesses antibacterial properties but is biocompatible, for artificial dressing applications. A sol-gel method was used for the preparation of the nano TiO2 powder with anatase phase. Several concentration ratios of TiO2 versus PLGA were analyzed to optimize the disinfection efficiency of the composite biomaterial. The antibacterial activity of the fabricated TiO2/PLGA composite was measured against Staphylococcus aureus and Escherichia coli. To evaluate the feasibility of the biomaterial on wound healing in vitro, human keratinocytes (HaCaTs), fibroblasts (L929s), and bovine carotid artery endothelial cells (BECs) were seeded on the TiO2/PLGA composite biofilms. To investigate the histological effect of the biocompatible biofilm in vivo, a rat subcutaneous implantation was performed. Our results show that TiO2/PLGA composite biofilms containing 10% TiO2 nanoparticles have an effective antibacterial property, a good survival rate on HaCaTs and L929s, and relative safe stability in tissue implantation. FROM THE CLINICAL EDITOR This study reports the development of titanium dioxide-polylactic-co-glycolic acid composite biofilms, which possess antibacterial properties and are biocompatible for dressing applications, as demonstrated in a model system.

Stimulation of wound healing by PU/hydrogel composites containing fibroblast growth factor-2

In this study, polyurethane (PU)/hydrogel composites were fabricated for wound healing applications. The hydrogel is a copolymer of thermosensitive N-isopropyl acrylamide (NIPAAm) and acrylic acid (AAc). γ-ray irradiation was employed to simultaneously copolymerize NIPAAm with AAc and graft the hydrogel onto porous PU. Fibroblast growth factor-2 (FGF-2) was incorporated into the composite to facilitate wound healing. The physical properties of the composites were characterized, the in vitro release of FGF-2 was examined, and in vivo tests were conducted. The results indicate that the thermosensitive hydrogel can absorb most of the wound exudates due to its high water uptake ability. Due to its thermosensitive properties, the PU/hydrogel composite is easier to strip off than that of commercial wound dressing, which prevents additional injury to the wound when replacing the wound dressing. In vivo results show that the PU/hydrogel composite incorporating FGF-2 could accelerate wound healing and reduce scar formation.

Anti-angiogenic properties of coenzyme Q0 through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling in TNF-α-activated human endothelial cells

Various coenzyme Q (CoQ) analogs have been reported as anti-inflammatory and antioxidant substances. However, coenzyme Q0 (CoQ0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone), a novel quinone derivative, has not been well studied for its pharmacological efficacies, and its response to cytokine stimulation remains unclear. Therefore, we investigated the potential anti-angiogenic properties of CoQ0 in human endothelial (EA.hy 926) cells against tumor necrosis factor-α (TNF-α) stimulation. We found that the non-cytotoxic concentrations of CoQ0 (2.5-10μM) significantly suppressed the TNF-α-induced migration/invasion and tube formation abilities of endothelial cells. CoQ0 suppressed TNF-α-induced activity and protein expressions of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) followed by an abridged adhesion of U937 leukocytes to endothelial cells. CoQ0 treatment remarkably downregulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) possibly through suppressed I-κBα degradation. Furthermore, CoQ0 triggered the expressions of heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCLC), followed by an increased nuclear accumulation of NF-E2 related factor-2 (Nrf2)/antioxidant response element (ARE) activity. In agreement with these, intracellular glutathione levels were significantly increased in CoQ0 treated cells. More interestingly, knockdown of HO-1 gene by specific shRNA showed diminished anti-angiogenic effects of CoQ0 against TNF-α-induced invasion, tube formation and adhesion of leukocyte to endothelial cells. Our findings reveal that CoQ0 protective effects against cytokine-stimulation are mediated through the suppression of MMP-9/NF-κB and/or activation of HO-1 signaling cascades. This novel finding emphasizes the pharmacological efficacies of CoQ0 to treat inflammation and angiogenesis.

Brain tumor senescence might be mediated by downregulation of S-phase kinase-associated protein 2 via butylidenephthalide leading to decreased cell viability

Developing an effective drug for treating human glioblastoma multiform (GBM) has been investigated persistently. A pure compound butylidenephthalide (BP), isolated from Angelica sinensis, has been shown the activities to arrest the growth and initiate apoptosis of GBM in our previous reports. In this study, we further demonstrated that BP treatment accelerates the cell senescence in a dose-dependent manner in vitro and in vivo. S-phase kinase-associated protein 2 (Skp2), a proto-oncogene, is generally upregulated in cancer. We found that it was downregulated in BP-treated GBM cells. The downregulation of Skp2 is parallel with increasing p16 and p21 expression which causes G0/G1 arrest and tumor cell senescence. We also found that restoring the Skp2 protein level by exogenous overexpression prevents the BP-induced cell senescence. Therefore, the linkage between cell senescence and Skp2 expression is strengthened. Promoter binding analysis further detailed that the BP-mediated SP1 reduction might involve in the Skp2 downregulation. In summary, these results emphasize that BP-triggered senescence in GBM cells is highly associated with its control on Skp2 regulation.

pH-Sensitive Hollow Alginate-Chitosan Hydrogel Beads for Bitter Gourd Delivery

Chitosan-alginate hydrogel beads with hollow structure were successfully prepared by dropping method for controlling delivery of bitter gourd (BG). Loading efficiency and loading content of the beads are 97.8% and 86.4%, respectively. Swelling accompanied with degradation behavior suggests the beads have pH-sensitive characteristics. In vitro release study reveals that the release behavior of these beads is environmental oriented. The MTS test demonstrates the hydrogel beads have good cytocompatibility and do not compromise cell viability. Finally, in vivo study confirms that hollow hydrogel beads have controlled and sustained release capability.

Poly(acrylic acid)–chitosan–silica hydrogels carrying platelet gels for bone defect repair

Most hydrogels derived from either natural or synthetic sources suffer from the lack of mechanical strength. In this study, high strength poly(acrylic acid)-chitosan-silica (PAA-Ch-Si) hydrogels were prepared by UV polymerization for tissue engineering applications. Compressive strength up to 42 MPa can be achieved by the formation of an interpenetrating network (IPN) structure between PAA and chitosan with nano-silica as the filler. The preliminary cell culture of osteoblast cells (7F2) on PAA-Ch-Si hydrogels indicates good biological safety. The growth factor (platelet glue) is fast and completely released from PAA-Ch-Si hydrogel scaffolds within 620 min. The scaffold starts to degrade after eight months in vitro. Histological examinations demonstrate that the hydrogel incorporated with growth factors and osteoblast cells can promote cell migration. All these results illustrate that PAA-Ch-Si hydrogels are beneficial for tissue engineering applications and can be used as scaffolds for bone defect repair.

Biopolymer coated gold nanocrystals prepared using the green chemistry approach and their shape-dependent catalytic and surface-enhanced Raman scattering properties

This study deals with the preparation of multi-shaped nanoscale gold crystals under synthetically simple, green, and efficient conditions using a seed-mediated growth approach in the presence of hyaluronic acid (HA). These highly biocompatible multi-shaped gold nanocrystals were examined to evaluate their catalytic and surface enhanced Raman scattering (SERS) properties. The results show that the size and shape of the nanocrystals are mainly correlated to the amount of seed, seed size, HA concentration, and reaction temperature. Gold seeds accelerate the reduction of the gold precursor to form gold nanocrystals using HA. The HA serves as a reducing agent and a growth template for the reduction of Au(III) and nanocrystal stabilization. The multi-shaped gold nanocrystals showed superior catalytic properties and higher SERS performance. The simple, green approach efficiently controls the nanocrystals and creates many opportunities for future applications.

Taiwanin A targets non-steroidal anti-inflammatory drug-activated gene-1 in human lung carcinoma

Taiwanin A (α,β-bis(piperonylidene)-γ-butyrolactone) is extracted from Taiwania cryptomerioides. Taiwanin A is extracted from tree bark and exhibits antitumor activity in breast, liver, and lung cancer cell lines. The objective of this study was to demonstrate the cytotoxicity of Taiwanin A against tumor cells by increasing the expression of non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1). NAG-1 has been reported to exhibit antitumor and proapoptotic activities, suggesting potential use in cancer therapy. Inhibiting NAG-1 mRNA expression in A549 reduced the cytotoxicity caused by Taiwanin A. Furthermore, the c-Jun-N-terminal kinase/Ste20-related protein proline/alanine-rich kinase (JNK/SPAK) pathway played a key role in the influence of NAG-1 on cell viability, whereas the addition of the JNK pathway inhibitor SP600125 resulted in an inhibitory effect on NAG-1 and recovery of Taiwanin-A-treated cells. A xenograft tumor model demonstrated that Taiwanin A dose-dependently significantly decreases tumor-mediated growth in nude mice by increasing the NAG-1 expression accompanying tumor apoptosis. These data supported the hypothesis that Taiwanin A inhibits lung carcinoma growth by increasing NAG-1 expression through the JNK pathway both in vivo and in vitro. This result can contribute to a compound design for increasing cytotoxicity activity in the future.