Yu-Mi Jeon

Antimicrobial photodynamic therapy using chlorin e6 with halogen light for acne bacteria-induced inflammation.

AIMS The present study was designed to evaluate the therapeutic potential of antimicrobial photodynamic therapy (PDT) using chlorin e6 with halogen light against acne bacteria-induced inflammation. MAIN METHODS Highly purified chlorin e6 (Ce6), as a second generation photosensitizer, was synthesized from Spirulina chlorophyll. To evaluate the antimicrobial property of Ce6-mediated PDT with halogen light, the broth microdilution method and two-color fluorescence assay were used. The free radicals generated upon irradiating Ce6 with halogen light were measured using 2,7-dichlorofluorescin diacetate. Propionibacterium acnes was intradermally injected into the left ear of the ICR mice, and the anti-inflammatory effect of Ce6-mediated PDT with halogen light was measured by the histological examination. The expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) as well as pro-inflammatory cytokines were also measured by Western blotting. KEY FINDINGS Chlorin e6-mediated PDT with halogen light (30,000 lx) inactivated various skin bacteria, including P. acnes in a dose-dependent manner. The MIC99 value against P. acnes (KCTC3314) of Ce6 with light was >0.49 μg/ml, whereas the MIC99 for Ce6 alone was >31.25 μg/ml. Ce6-mediated PDT suppressed the expression of P. acnes-induced pro-inflammatory cytokines and iNOS, but not COX-2 in a mouse model. SIGNIFICANCE This study showed a remarkable therapeutic effect of chlorin e6-mediated PDT with halogen light against P. acnes-induced inflammation. Our results suggest for the first time the potential of Ce6-mediated PDT with halogen light as a more effective and safer alternative treatment to antibiotic therapy against pathogenic infections of the skin.

The effects of TiO2 nanoparticles on the protein expression in mouse lung

In this study, the differentially expressed proteins by titanium dioxide nanoparticles (TiO2 NPs) in mouse lung were examined via proteomic approach to better understand the molecular mechanism by which TiO2 NPs could induce toxicities at the protein level. We identified eight proteins that exhibited more than two-fold changes in expression by TiO2 NPs. Of these, five proteins, named cytoplasmic aconitase, L-lactate dehydrogenase A chain, carbonic anhydrase 1, pyruvate kinase isoform M2 and peroxiredoxin 6 displayed increased intensities in TiO2 NP-exposed lungs, while three proteins, named heat shock protein, moesin and apolipoprotein A-1 precursor, showed reduced intensities.

Proteomic profiling of the differentially expressed proteins by TiO2 nanoparticles in mouse kidney

We investigated the proteins showing differential expression in response to TiO2 nanoparticles in mouse kidney using a proteomic approach to better understand the molecular mechanism by which TiO2 nanoparticles-induced nephrotoxicity at the protein level. More than 1,100 protein spots in mouse kidney were detected by the two-dimensional gel eletrophoresis and comparative analysis revealed that the expression of 11 proteins were changed by more than 2 fold in response to TiO2 nanoparticles. Of these, 10 were up-regulated and 1 was down-regulated upon treatment with TiO2 nanoparticles.

Toxicoproteomic identification of TiO2 nanoparticle-induced protein expression changes in mouse brain

A proteomic analysis of the proteins in mouse brain that were differentially expressed in response to TiO2 nanoparticles was conducted to better understand the molecular mechanism of TiO2 nanoparticle-induced brain toxicity at the protein level. A total of 990 proteins from mouse brain were resolved by two-dimensional gel electrophoresis. A comparative proteomic analysis revealed that the expression levels of 11 proteins were changed by more than 2-fold in response to TiO2 nanoparticles: eight proteins were upregulated and three were downregulated by TiO2 nanoparticles. In addition, the activities of several antioxidative enzymes and acetylcholine esterase were reduced in TiO2 nanoparticle-exposed mouse brain. The protein profile alterations seem to be due to an indirect effect of TiO2 nanoparticles, because TiO2 nanoparticles were not detected in the brain in this investigation.

Chlorin e6-Mediated Photodynamic Therapy Suppresses P. acnes-Induced Inflammatory Response via NFκB and MAPKs Signaling Pathway.

Photodynamic therapy (PDT), consisting of photosensitizer, light, and oxygen has been used for the treatment of various diseases including cancers, microbial infections and skin disorders. In this study, we examined the anti-inflammatory effect of chlorin e6-mediated PDT in P. acnes-infected HaCaT cells using photosensitizer chlorin e6 (Ce6) and halogen light. The live and heat-killed P. acnes triggered an upregulation of inflammatory molecules such as iNOS, NO, and inflammatory cytokine in HaCaT cells and mouse model. Ce6-mediated PDT notably downregulated the expression of these inflammatory molecules in vitro and in vivo. Similarly, chlorin e6-mediated PDT was capable of regulating inflammatory response in both live and heat killed S. epidermidis exposed HaCaT cells. Moreover, phosphorylation of p38, JNK, and ERK were reduced by Ce6-mediated PDT. Ce6-mediated PDT also reduced the phosphorylation of IKKα/β, IĸBα and NFκB p65 in P. acnes-stimulated HaCaT cells. In addition, the dramatic increase in the nuclear translocation of NFκB p65 observed upon stimulation with P. acnes was markedly impaired by Ce6-based PDT. This is the first suggestion that Ce6-mediated PDT suppresses P. acnes-induced inflammation through modulating NFκB and MAPKs signaling pathways.

Proteomic analysis of hepatotoxicity induced by titanium nanoparticles in mouse liver

Differentially expressed proteins in mouse liver caused by toxicity of titanium nanoparticles (TiO2 NPs) were screened. More than 1,400 protein spots in mouse liver were detected by twodimensional gel electrophoresis, and 15 proteins that showed greater than 2-fold expressional changes in response to TiO2 NPs were identified by liquid chromatography-tandem mass spectrometry. Of these, 12 proteins were down-regulated and 3 proteins were up-regulated upon treatment with TiO2 NPs. The 15 differentially expressed proteins could be used for detection of inflammation, apoptosis, and antioxidative reaction for treatment of acute hepatic damage by TiO2 NPs.

Airborne nanoparticles (PM0.1) induce autophagic cell death of human neuronal cells

Airborne nanoparticles PM0.1 (<100 nm in diameter) were collected and their chemical composition was determined. Al was by far the most abundant metal in the PM0.1 followed by Zn, Cr, Mn, Cu, Pb and Ni. Exposure to PM0.1 resulted in a cell viability decrease in human neuronal cells SH‐SY5Y in a concentration‐dependent manner. Upon treatment with N‐acetylcysteine, however, cell viability was significantly recovered, suggesting the involvement of reactive oxygen species (ROS). Cellular DNA damage by PM0.1 was also detected by the Comet assay. PM0.1‐induced autophagic cell death was explained by an increase in the expression of microtubule‐associated protein light chain 3A‐ІІ (LC3A‐ІІ) and autophagy‐related protein Atg 3 and Atg 7. Analysis of 2‐DE gels revealed that six proteins were upregulated, whereas eight proteins were downregulated by PM0.1 exposure. Neuroinflammation‐related lithostathine and cyclophilin A complexed with dipeptide Gly‐Pro, autophagy‐related heat shock protein gp96 and neurodegeneration‐related triosephosphate isomerase were significantly changed upon exposure to PM0.1. These results, taken together, suggest that PM0.1‐induced oxidative stress via ROS generation plays a key role in autophagic cell death and differential protein expressions in SH‐SY5Y cells. This might provide a plausible explanation for the underlying mechanisms of PM0.1 toxicity in neuronal cells and even the pathogenesis of diseases associated with its exposure. Copyright

Inhibitory effect of Acanthopanax extract on the dopaminergic neuroblastoma cells against rotenone-induced toxicity

Abstract During screening of Korean indigenous medicinal herbs with anti-neurodegenerative activities, we found that the extract of Acanthopanax divaricatus vat. albeofructus could inhibit rotenone-induced DNA and cell damage in neuroblastoma cells. A simple in vitro model developed for the study of possible mechanisms underlying neurodegeneration in Parkinson’s disease includes the administration of rotenone to the human dopaminergic neuroblastoma cell line, SH-SY5Y. In this investigation, rotenone induced oxidative DNA damage of lymphocytes as expected. However, the oxidative DNA damage was inhibited in vitro upon treating Acanthopanax extract. Moreover, Acanthopanax extract resulted in the inhibitory activities against cell damage, ROS generation and chromatin condensation by rotenone.

Effects of Ore Minerals on the Damages of Animal Cells

In this study, we investigated the suppressive effects of ore minerals on the allergic cell damages and oxida- tive cell damages. The ore minerals significantly reduced the productions of tumor necrosis factor-alpha (TNF- ) and interleukin-4 (IL-4) in rat basophilic leukemia cells challenged with 2,4-dinitrophenol-bovine serum α albumin (DNP-BSA). Lipoxygenase activity was also reduced by the ore minerals. Moreover, the ore minerals showed weak protective effects on the oxidative damage induced by hydrogen peroxide in pig kidney cells and retinal ganglion cells. Photohemolysis of erythrocytes in the presence of rose-bengal as a sensitizer was also inhibited by ore minerals. These results suggest that the ore minerals may be useful as the protectant for allergic and oxidative cell damages.