Search

Block copolymer composed of carboxymethyl dextran (CMDex) and methoxy poly(ethylene glycol) (MPEG) (abbreviated as CMDexPEG) was synthesized and doxorubicin (DOX) was conjugated with carboxyl groups of CMDexPEG. DOX-conjugated CMDexPEG block copolymer formed nanoparticles in water with sizes less than 100 nm. DOX-conjugated nanoparticles enhanced DOX delivery to the DOX-resistant CT26 cells and showed higher anticancer activity in vitro. DOX-conjugated nanoparticles inhibited growth of CT26 solid tumor at tumor-bearing mouse model study. In near infrared (NIR)-dye study, nanoparticles were retained in the tumor tissues for a longer period.

The increasing prevalence of methicillin-resistant Staphylococcus aureus has become a major public health threat. While lactobacilli were recently found useful in combating various pathogens, limited data exist on their therapeutic potential for S. aureus infections. The aim of this study was to determine whether Lactobacillus salivarius was able to produce bactericidal activities against S. aureus and to determine whether the inhibition was due to a generalized reduction in pH or due to secreted Lactobacillus product(s). We found an 8.6-log10 reduction of planktonic and a 6.3-log10 reduction of biofilm S. aureus. In contrast, the previously described anti-staphylococcal effects of L. fermentum only caused a 4.0-log10 reduction in planktonic S. aureus cells, with no effect on biofilm S. aureus cells. Killing of S. aureus was partially pH dependent, but independent of nutrient depletion. Cell-free supernatant that was pH neutralized and heat inactivated or proteinase K treated had significantly reduced killing of L. salivarius than with pH-neutralized supernatant alone. Proteomic analysis of the L. salivarius secretome identified a total of five secreted proteins including a LysM-containing peptidoglycan binding protein and a protein peptidase M23B. These proteins may represent potential novel anti-staphylococcal agents that could be effective against S. aureus biofilms., Pathogens and Disease, 75 (2), ISSN:2049-632X

In this study, we synthesized caffeic acid (CFA)-conjugated chitosan (ChitoCFA) as an anti-cancer compound. CFA was conjugated to the amine groups of chitosan (ChitoCFA) and its chemical composition was confirmed using (1)H nuclear magnetic resonance spectra, which indicates that specific peaks of CFA was observed at ChitoCFA conjugates. The anti-cancer effects of CFA and ChitoCFA were studied using CT26 colorectal carcinoma cells. In this cytotoxicity study, CFA and ChitoCFA revealed a dose-dependent decrease of cell viability while chitosan had lower cytotoxicity against tumor cells. CFA and ChitoCFA also proved an anti-proliferative effect against tumor cells. In comparison with CFA, ChitoCFA may accelerate an apoptosis of tumor cells. Furthermore, ChitoCFA demonstrated good anti-invasive efficacy at Matrigel(®) invasion assay against tumor cells. We suggest that ChitoCFA is a promising candidate as an anti-cancer compound.

In this paper, we fabricate planar-type Silicon-Oxide-High-k-Oxide-Silicon (SOHOS) and the planar-type SOHOS devices with N2 implantation of 3 x 10(15) dose in a tunneling oxide to determine the impact of N2 implantation in the tunneling oxide of a memory device. The N2 implantation device has better retention characteristics than the device with no implantation. In order establish the correlation between N2 implantation and retention characteristic improvement, the low frequency noise (1/f noise) characteristic is investigated. The normalized drain current noise (S(ID)/I(D)2) level of the N2 implantation device is higher than that of the device with no implantation, which means that N2 implantation causes more trap formation near the interface. Considering that N2 implantation does not affect the DC transfer characteristics, such as mobility and sub-threshold slope, this finding indicates that the increase in the 1/f noise level is due to oxide traps rather than to interface traps. Therefore, the retention characteristic improvement in the N2 implantation device can be explained by the generation of higher number of oxide traps and an increase in the potential barrier blocking the leakage path in the tunneling oxide.

Daily use of probiotic chewing gum might have a beneficial effect on oral health, and it is important that the viability of the probiotics be maintained in this food product. In this study, we examined the stability of probiotic chewing gum containing Weissella cibaria. We evaluated the effects of various factors, including temperature and additives, on the survival of freeze-dried probiotic W. cibaria powder. No changes in viability were detected during storage at 4℃ for 5 months, whereas the viability of bacteria stored at 20℃ decreased. The stability of probiotic chewing gum decreased steadily during storage at 20℃ for 4 weeks. The viability of the freeze-dried W. cibaria mixed with various additives, such as xylitol, sorbitol, menthol, sugar ester, magnesium stearate, and vitamin C, was determined over a 4-week storage period at 20℃. Most of the freeze-dried bacteria except for those mixed with menthol and vitamin C were generally stable during a 3-week storage period. Overall, our study showed that W. cibaria was more stable at 4℃ than that at 20℃. In addition, menthol and vitamin C had a detrimental effect on the storage stability of W. cibaria. This is the first study to examine the effects of various chewing gum additives on the stability of W. cibaria. Further studies will be needed to improve the stability of probiotic bacteria for developing a novel probiotic W. cibaria gum.

항생제 사용에 따라 구강내 세균들이 가지게 되는 내성의 발현이 문제가 될 수 있다. 어린이 치면세균막에서 치주질환의 원인균들과 흔히 사용하고 있는 항생제들에 대한 내성유전자의 출현율을 알아보고자 중합효소연쇄반응을 이용하여 조사하였다. 1. 치주질환 원인균의 출현율은 F. nucleatum 95.4%, T. forsythia 55.2% 이었으며, P. gingivalis 40.2%, A. actinomycetemcomitans 5.7%, T. denticola는 3.4% 순이었다. 2. 항생제 내성유전자의 출현율 조사에서 cephalosporin 분해효소인 cfxA는 100%에서 발견되었으며 ${\beta}$ -lactam 분해효소인 $bla_{TEM}$ 과 tetracycline 내성유전자인 tet(M)도 100%의 출현율을 보였다. tet(Q)는 88.5%, ${\beta}$ -lactam 분해효소인 $bla_{SHV}$ 는 29.9%, macrolide계 내성 ermF유전자는 87.4%, vancomycin 내성 vanA는 48.5%의 출현율을 보였다. Aminoglycoside에 대한 복합 내성을 보이는 aacA-aphD와 meticillin 내성유전자 mecA는 9.2%로 가장 낮은 출현율을 보였다. 3. 치주질환 원인균과 항생제 내성유전자와의 관련성 조사에서 T. forsythia와 $bla_{SHV}$ 간에 그리고 P. gingivalis와 vanA간 에 유의한 상관성이 있었다. 항생제 내성유전자 tet(Q)와 ermF (0.514)간에 중등도의 상관성을 나타내었으며, mecA와 vanA (0.25)간에 유의한 상관성을 나타내었다. 건강한 어린이들의 치면세균막에 다양한 치주질환 원인균들과 항생제 내성유전자들이 존재하며, 상호 관련성을 가지고 존재함을 보여주었다. 【The purpose of this study was to assess the prevalence of periodontopathic bacteria and resistance determinants from oral biofilm of children. Subgingival dental plaque was isolated from 87 healthy children, and PCR was performed to determine the presence of 5 periodontal pathogens including P. gingivalis, T. forsythia, T. denticola, F. nucleatum, A. actinomycetemcomitans, and nine resistance genes including tet(Q), tet(M), ermF, aacA-aphD, cfxA, $bla_{SHV}$ , $bla_{TEM}$ , vanA, mecA. 1. The prevalence of F. nucleatum, T. forsythia. and P. gingivalis was 95.4%, 55.2%, and 40.2%, respectively. In addition. the prevalence of A. actinomycetemc omitans was 5.7%, while T. denticola was 3.4%. 2. In analysis of antibiotic resistance determinants. cfxA, $bla_{TEM}$ and tet(M) were detected in all the samples tested. It was also found that the prevalence of tet(Q) showing tetracycline resistance. $bla_{SHV}$ associated with resistance to ${\beta}$ -lactams, ermF exhibiting erythromycin resistance, and, vanA resulting vancomycin resistance was 88.5%, 29.9% 87.4%, and 48.5%, respectively. The aacA-aphD gene showing resistance to aminoglycosides and mecA gene harboring methicillin resistance exhibited the lowest prevalence with 9.2%. 3. In a correlation analysis between periodontopathic pathogens and antibiotic resistance determinants, it was found that there was a significant correlation between T. forsythia and $bla_{SHV}$ . Also, P. gingivalis and vanA showed a correlation. Finally, tet(Q) and ermF showed a significant correlation (phi: 0.514) while mecA and vanA also showed a correlation(phi: 0.25).】

The aim of this study was to evaluate the antitumor effect of combinatorial targeted therapy with paclitaxel and all-trans retinoic acid (ATRA) nanoparticles in vitro. Paclitaxel-incorporated pullulan acetate (PA) nanoparticles were prepared by the nanoprecipitation-solvent evaporation method. ATRA-incorporated nanoparticles were prepared by dialysis using a methoxy poly(ethylene glycol)-grafted chitosan (ChitoPEG) copolymer. Particle sizes of paclitaxel-incorporated nanoparticles and ATRA-incorporated nanoparticles were about 160 nm and 60 nm, respectively. Nanoparticles were reconstituted in various aqueous media such as deionized water, phosphate-buffered saline, and fetal bovine serum-supplemented cell culture media. The combination of paclitaxel + ATRA (10 + 10 μg/mL) delivered by nanoparticles showed a synergistic antiproliferative effect against CT26 cells that was not observed with other combinations. Furthermore, the activity of MMP-2, a key enzyme in tumor cell invasion, was significantly decreased in cells treated with the combination of paclitaxel and ATRA while other combinations and single agents did not significantly affect its activity. A matrigel assay supported these results, indicating that paclitaxel/ATRA combination nanoparticles are effective for the inhibition of the invasion of tumor cells. The results of the present study suggest that combination treatment with paclitaxel and ATRA could be an effective treatment for the inhibition of tumor cell proliferation and invasion, and that nanoparticles are promising candidates for antitumor drug delivery.

Interactions between periodontal bacteria and human oral epithelial cells can lead to the activation and expression of a variety of inflammatory mediators in epithelial cells. Fusobacterium nucleatum is a filamentous human pathogen that is strongly associated with periodontal diseases. This study examined the effects of methyl gallate (MG) and gallic acid (GA) on the production of inflammatory mediators, interleukin (IL)-6 and IL-8, by oral epithelial cells stimulated by F. nucleatum. In a real-time reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay, live F. nucleatum induced high levels of gene expression and protein release of IL-6 and IL-8. The effects of MG and GA were examined by treating KB oral epithelial cells with MG and GA and stimulating them with F. nucleatum. MG and GA inhibited significantly the increases in the IL-6 and IL-8 gene and protein levels in a dose-dependent manner. These Compounds also inhibited the growth of F. nucleatum. No visible effects of MG and GA on the adhesion and invasion of KB cells by F. nucleatum were observed. In conclusion, both MG and GA inhibit IL-6 and IL-8 production from F. nucleatum-activated KB cells.

Actinobacillus actinoinycetemcomitans (A. actinomycetem-comitans) is an important pathogen casuing aggressive periodontitis. The present study was designed to investigate the chemokines expression regulated by A. actinomycetemcomitans lipopolysaccharide (LPS). Chemokines genes expression profiling was performed in Raw 264.7 cells by analyses of microarray and reverse transcription-polymerase chain reaction (RT-PCR). Microarray results showed that the induction of monocyte chemoattractant protein-1alpha (MCP-1alpha) and macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, MIP-1gamma, regulated upon activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein-2 (MIP-2), and interferon-gamma inducible protein 10 (IP 10) by A. actinomycetemcomitans LPS was increased to 12.5, 1.53, 9.09, 17.3, 2.82, 16.1, and 18.1 folds at 18 h, respectively. To check these chemokines expression by A. actinomycetemcomitans LPS, we examined gene expressions by RT-PCR, and found that the expression of MIP-1beta, MIP-1gamma, RANTES, MIP-2, and IP 10 was increased 107.1, 93.6, 106.8, 86.5, and 162.0 folds at 18 h, respectively. These results indicate that A. actinomycetemcomitans LPS stimulates the several chemokines expressions (MIP-1alpha, MIP-1beta, MIP-1gamma, RANTES, MIP-2, and IP 10) in Raw 264.7 cells.

Summary Background 5-Aminolaevulinic acid (ALA) and its esters act as precursors to the fluorescent photosensitizer protoporphyrin IX (PpIX) in photodynamic therapy (PDT). There is little information about how ALA and its esters induce PpIX synthesis and photodynamic effects in cell lines derived from the skin. Objectives We compared the amount of PpIX synthesis induced by ALA and its esters in skin cell lines, and evaluated the relationship of PpIX synthesis to photodynamic effects by ALA and its esters in vitro. Methods Four cell lines, including human epidermal keratinocytes (HEK), human dermal fibroblast (hF), A431, and TXM13 were used. Cell survival was evaluated by the MTT assay. Fluorescence spectroscopy was used to measure the amount of PpIX synthesis induced by ALA and its esters. Flow cytometry measured cell death induced by ALA- and its esters-mediated PDT. Results ALA and its esters were not toxic at concentrations lower than 2 mmol L−1 in all cell lines. PpIX synthesis was dose-dependent at low doses (0·01–0·1 mmol L−1), and ALA esters were more effective than ALA. Cell death occurred from necrosis rather than apoptosis just after light irradiation illumination on both ALA and its esters-treated cells. Cell death related more to PpIX synthesis than the irradiation light dose. Conclusions PpIX production by ALA and its esters was induced on both normal and malignant cell lines derived from the skin, and cell death of PDT responses is closely related to the amount of PpIX synthesis rather than to the irradiation dose.

This study was carried to investigate effects of gamma irradiation on the moisture, crude protein, crude lipid, 2-thiobarbituric acid (TBA) values, color stability, texture, and sensory properties of restructured pork jerky. Restructured pork jerky was irradiated at dose levels of 0, 3, 5, 7 and 10 kGy with a use Co-60 source. There were no significant differences in the moisture, crude protein, crude lipid contents, and TBA values. However, as doses of gamma irradiation increased, the redness (a-value) of restructure pork jerky increased whereas shear force of restructure pork jerky was decreased by gamma irradiation. Sensory evaluation showed that sensory scores were reduced by gamma irradiation. Therefore, gamma irradiation could be an effective means to improve color and texture of restructured pork jerky, but only with proper consideration for sensory quality.

Caffeic acid-conjugated chitosan (ChitoCFA) and carboxymethyl dextran-b-poly(ethylene gycol) (CMD-PEG) copolymer were synthesized to fabricate self-organized nanoparticles. Nanoparticles were formed through ion-complex formation between ChitoCFA and CMD-PEG. Nanoparticles have small sizes ranged about 80 nm~300 nm with spherical shapes. Doxorubicin (DOX) was incorporated into the nanoparticles of ChitoCFA/CMD complexes. Particle sizes were increased according to the contents of drug. At drug release experiment, DOX was continuously released over 96 h. Anticancer acticity of nanoparticles were assessed with DOX-resistant CT26 cells. CT26 cells treated with DOX-incorporated nanoparticles revealed strong fluorescence intensity while free DOX revealed weak fluorescence intensity, indicating that DOX-loaded nanoparticles of ChitoCFA/CMD are promising vehicle for anticancer drug targeting.

Background Since aggressive cancer cells highly express the CD44 receptor compared to normal cells, hyaluronic acid (HA) can be used for CD44 targeting molecule. Since glutathione (GSH) level is normally elevated in the intracellular compartment and in the tumor cell, the fact that disulfide bond can be cleaved by GSH is widely used for intracellular drug delivery. Methods HA was connected with poly(dl-lactide-co-glycolide) (PLGA) using disulfide linkage, and then a diblock copolymer (HAssLG) was prepared. Doxorubicin (DOX)-loaded HAssLG nanoparticles were prepared by dialysis procedures. Results and Discussion DOX-loaded HAssLG nanoparticles have spherical shapes with small particle size of less than 300 nm. In fluorescence measurement, DOX was dose-dependently liberated from nanoparticles by the addition of GSH. DOX release rate from HAssLG nanoparticles was increased by the addition of GSH. To confirm CD44 receptor-mediated endocytosis of nanoparticles, CD44-positive MDA-MB231 cells were employed and fluorescence intensity was strong when nanoparticles were treated to tumor cells. However, fluorescence intensity was significantly decreased through blocking of the CD44 receptor by pretreatment of cells with free HA. Fluorescence intensity of cells was increased again when GSH was added, indicating that HAssLG nanoparticles have CD44 receptor targetability and potential of redox-responsive drug delivery. For animal imaging study, CD44-positive MDA-MB231 cells and CD44-negative NIH3T3 cells were simultaneously implanted into the right flank and left flank of mice, respectively. Fluorescence intensity was significantly stronger at tumor mass of MDA-MB231 cells than solid mass of NIH3T3 cells, indicating that HAssLG nanoparticles were specifically delivered to tumor cells. Conclusions The results indicated that HAssLG nanoparticles have specificity against the CD44 receptor and can be used for anticancer drug targeting. We recommend HAssLG nanoparticles as a promising vehicle for cancer drug targeting.

Background Nanoparticles have been extensively investigated for targeted delivery of anticancer drugs. Since the folate receptor is universally over-expressed on the tumor cell membrane, folic acid is often used to modify the fate of nanoparticles in biologicals. Methods To fabricate targetable nanoparticles, folic acid was conjugated to a pullulan backbone and poly(DL-lactide-co-glycolide) (PLGA) (abbreviated as FAPuLG) was conjugated. KB cells and NIH3T3-cell-bearing mice were prepared to prove folate receptor targeting of FAPuLG nanoparticles. Results and discussion Nanoparticles of FAPuLG copolymer that self-assembled in water were small with diameters

Poly( dl -lactide-co-glycolide)-graft pullulan (PuLG) was synthesized to produce a hydrophobically modified polysaccharide. Specific pullulan and poly( dl -lactide-co-glycolide) (PLGA) (abbreviated as PuLG) appeared in the peaks of the PuLG spectra on 1 H NMR spectroscopy, suggesting that PLGA was successively grafted to the pullulan backbone. PuLG nanospheres have a round shape with a particle size of about 75–150 nm. From the fluorescence excitation spectra in a fluorescence probe study, the critical association concentration (CAC) values were determined to be 0.017 g/l for PuLG-1, 0.0054 g/l for PuLG-2, and 0.0047 g/l for PuLG-3. The drug contents of the PuLG nanospheres were approximately 20–30% (w/w). As the drug contents of PuLG nanospheres increased, the drug release rate from nanospheres decreased. The drug release rate from PuLG nanospheres was delayed as the molecular weight of PuLG increased. PuLG copolymer with higher graft ratio of PLGA showed slower degradation rate rather than that with lower graft ratio. Since degradation rate of PuLG was taken over 1 month, drug release was governed by diffusion mechanism rather than degradation mechanism.

Polycaprolactone (PCL) macromer was obtained by the reaction of PCL diol with acryloyl chloride and confirmed using Fourier transform infrared and nuclear magnetic resonance spectrometer. Novel degradable PCL networks were prepared through photopolymerization of the PCL macromer. Thermal, mechanical, and morphological characteristics as well as degradability and biocompatibility of the PCL networks were investigated. Differential scanning calorimetry showed that the melting temperature and the calculated weight average crystallinity of PCL networks were decreased with a decrease of molecular weight of PCL diols due to the increased crosslinking density. Thermal stability of PCL networks was higher than that of PCL diols. PCL networks showed faster degradation, and higher compressive modulus and compressive recovery ratios than those of PCL itself because of their low crystallinity and the modification of terminal groups. The porosity of the PCL networks can be controlled by the amounts and size of porogen used. MG-63 osteoblast cell was attached and proliferated on PCL networks. PCL networks therefore may have considerable potential as scaffold for tissue engineering.

Drug-impregnated polyelectrolyte complex (PEC) sponge composed of chitosan and sodium alginate was prepared for wound dressing application. The morphological structure of this wound dressing was observed to be composed of a dense skin outer layer and a porous cross-section layer by scanning electron microscopy (SEM). Equilibrium water content and release of silver sulfadiazine (AgSD) could be controlled by the number of repeated in situ PEC reactions between chitosan and sodium alginate. The release of AgSD from AgSD-impregnated PEC wound dressing in PBS buffer (PH = 7.4) was dependent on the number of repeated in situ complex formations for the wound dressing. The antibacterial capacity of AgSD-impregnated wound dressing was examined in agar plate against Pseudomonas aeruginosa and Staphylococcus aureus. From the behavior of antimicrobial release and the suppression of bacterial proliferation, it is thought that the PEC wound dressing containing antimicrobial agents could protect the wound surfaces from bacterial invasion and effectively suppress bacterial proliferation. In the cytotoxicity test, cellular damage was reduced by the controlled released of AgSD from the sponge matrix of AgSD-medicated wound dressing. In vivo tests showed that granulation tissue formation and wound contraction for the AgSD plus dihydroepiandrosterone (DHEA) impregnated PEC wound dressing were faster than any other groups.

Chlorophyllin (CHL), a chlorophyll-derivative, exhibits several beneficial properties, including antibacterial, antioxidant, and anticancer activities. However, its antibacterial and anti-inflammatory activities against Propionibacterium acnes have not been described. The antibacterial activity of this compound was evaluated in vitro using the broth microdilution method. CHL had an inhibitory effect on the growth of P. acnes (MIC = 100 μM). In a real-time reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay, CHL significantly decreased interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) production in a dose-dependent manner, decreasing both mRNA and protein levels for these chemokines in THP-1 cells indicating the anti-inflammatory effects of it. To investigate the molecular mechanisms underlying the anti-inflammatory properties of CHL in THP-1 cells stimulated by P. acnes, we used western blotting to analyze the effect of CHL on activation of the nuclear factor (NF)-κB. CHL inhibited P. acnes-induced IL-8 and MCP-1 production via blockade of NF-κB activation in THP-1 cells. Therefore, based on these results, we suggest that CHL is a useful agent to control the growth of P. acnes involved in acne inflammation and prevent acne.

The interaction between Lactobacillus reuteri, a probiotic bacterium, and oral pathogenic bacteria have not been studied adequately. This study examined the effects of L. reuteri on the proliferation of periodontopathic bacteria including Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, and Tannerella forsythia, and on the formation of Streptococcus mutans biofilms. Human-derived L. reuteri strains (KCTC 3594 and KCTC 3678) and rat-derived L. reuteri KCTC 3679 were used. All strains exhibited significant inhibitory effects on the growth of periodontopathic bacteria and the formation of S. mutans biofilms. These antibacterial activities of L. reuteri were attributed to the production of organic acids, hydrogen peroxide, and a bacteriocin-like compound. Reuterin, an antimicrobial factor, was produced only by L. reuteri KCTC 3594. In addition, L. reuteri inhibited the production of methyl mercaptan by F. nucleatum and P. gingivalis. Overall, these results suggest that L. reuteri may be useful as a probiotic agent for improving oral health.

Weissella cibaria isolated from human saliva produces a soluble glucan that predominantly has alpha-1,6-glucosidic type linkages. Using degenerated primers that were selected based on the amino acid sequences of conserved regions from known glucansucrases, a single 2.7-kb fragment was isolated. In subsequent steps, a 4969-bp product was obtained using inverse PCR. The coding region for the glucansucrase gene (dsrWC) consisted of a 4419-bp ORF that encoded a 1472-amino acid protein with a calculated molecular mass of 161.998 Da. The produced DSRWC glucansucrases exhibited similarity with the enzymes of the glucosylhydrolase family 70, which includes the Lactobacillus fermentum glucansucrase. The expressed recombinant DSRWC (rDSRWC) synthesized oligosaccharides in the presence of maltose or isomaltose as an acceptor and the synthesized products included alpha-1,6-linked glucosyl residues in addition to the maltosyl or isomaltosyl residue. rDSRWC synthesized water-soluble polymers using sucrose as substrate. According to the (13)C-nuclear magnetic resonance analysis, the polymer that was synthesized by rDSRWC was a linear dextran, which formed predominately alpha-1,6-glucosidic linkages. This is the first report on the molecular characterization of glucansucrase from a W. cibaria strain.

This study examined the ability of methyl gallate (MG) and gallic acid (GA), the main compounds of gallo-tannins in Galla Rhois, to inhibit the proliferation of oral bacterial and the in vitro formation of Streptococcus mutans biofilms. The antimicrobial activities of these compounds were evaluated in vitro using the broth microdilution method and a beaker-wire test. Both MG and GA had inhibitory effects on the growth of cariogenic (MIC

Sang Joon Lee,1,* Young-Il Jeong,2,* Hyung-Kyu Park,3 Dae Hwan Kang,2,4 Jong-Suk Oh,3 Sam-Gyu Lee,5 Hyun Chul Lee31Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 2Biomedical Research Institute, Pusan National University Hospital, Busan, 3Department of Microbiology, Chonnam National University Medical School, Gwangju, 4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, 5Department of Physical and Rehabilitation Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea*These authors contributed equally to this workBackground: Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol) (MPEG)-doxorubicin (DOX) conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting.Methods: Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP). Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP). Nanoparticles were then prepared using a dialysis procedure.Results: The synthesized DendGDP was confirmed with 1H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and revealed stronger fluorescence intensity than at other body sites while doxorubicin and DendDP nanoparticles showed strong fluorescence intensity in the various organs, indicating that DendGDP has cathepsin B sensitivity.Conclusion: DendGDP is sensitive to cathepsin B in tumor cells and can be used as a cathepsin B-responsive drug targeting strategy. We suggest that DendGDP is a promising vehicle for cancer cell targeting.Keywords: cathepsin B, CT26 cell, enzyme-sensitive dendrimer, tumor targeting, tetra peptide

Aims: The objective of this study was to characterize the inhibitory effects of Weissella cibaria isolates on volatile sulphur compounds (VSC) production both in vitro and in vivo. Material and Methods: We isolated and identified three hydrogen peroxide-generating lactobacilli from children's saliva, and assessed their inhibitory effects on VSC production and Fusobacterium nucleatum proliferation. Clinical studies were conducted with 46 subjects in order to measure the VSC of their mouth air. Results: These lactobacilli were identified as W. cibaria. These isolates inhibited the production of VSC by F. nucleatum (p

In the present study, we evaluated the ability of Weissella cibaria isolated from the oral cavity to coaggregate with Fusobacterium nucleatum, and the adhesiveness of these strains to epithelial cells. W. cibaria efficiently coaggregated with F. nucleatum, and adhered to epithelial cells. We tested the effects of various factors on the coaggregation. The coaggregation and adhesiveness of W. cibaria disappeared upon exposure to pronase or LiCl, suggesting that proteinaceous components on the surface of W. cibaria mediated the coaggregation and adhesiveness. In conclusion, W. cibaria may serve as a potential probiotic with the ability to establish an oral flora protecting against oral pathogens.

ABA-type block copolymers (abbreviated as LEL) composed of poly(L-leucine) (PLL) as the A component and poly(ethylene glycol) (PEG) as the B component were synthesized by ring-opening polymerization of L-leucine N-carboxyanhydride initiated by primary amino group located at both ends of PEG chain. A silver sulfadiazine (AgSD)-impregnated wound dressing of sponge type was prepared by the lyophilization method. Morphological structure of this wound dressing by scanning electron microscopy was observed to be composed of a dense skin layer and a porous inner layer. Equilibrium water content of LEL wound dressing increased with an increase in PEG content in the block copolymer due to the hydrophilicity of PEG. AgSD release from AgSD-impregnated wound dressing in PBS buffer (pH = 7.4) was dependent on PEG content in the block copolymer. Release of AgSD was increased in proportion to the PEG content in the copolymer. Antibacterial capacity of AgSD-impregnated wound dressing was examined in agar plate against Pseudomonas aeruginosa and Staphylococcus aureus. It was found that the suppression of bacterial proliferation in the wound dressing was dependent upon the PEG content. In cytotoxicity test, cell damage did not occur by the release of AgSD from the LEL sponge matrix of AgSD-medicated wound dressing. In in vivo test, granulous tissue formation and wound contraction for the AgSD- and dehydroepiandrosterone-impregnated LEL-2 wound dressing were faster than for any other groups.

Propionibacterium acnes is the most common causative agent of acne. Staphylococcus epidermidis is another major bacterial strain to be found in acne lesions. Two strains of lactic acid bacteria (LAB) were isolated from normal inhabitants of humans, which inhibited the proliferation of P. acnes and S. epidermidis. The growth of P. acnes and S. epidermidis was decreased by 4-log scales after incubation for 24 h with LAB isolates, whereas the growth rate of selected LAB isolates were not affected by these pathogenic bacteria. This antibacterial activity of LAB isolates was related to lactic acids, hydrogen peroxide and bacteriocin-like compound production. Two LAB isolates efficiently adhered to human keratinocytes HaCaT and were identified by API 50 CHL medium kit and 16S rDNA partial sequencing analysis. The similarity of 16S rDNA sequences between one isolate and Lactobacillus salivarius subsp. salicinius was 100%, which suggests that they were L. salivarius subsp. salicinius. On the other hand, 16S rDNA sequence similarity between the other isolate and Lactobacillus fermentum was 99.04%, which indicates that it was L. fermentum. In conclusion, these results demonstrate that the two LAB strains isolated from human body were identified as L. salivarius subsp. salicinius and L. fermentum, which inhibit the proliferation of P. acnes and S. epidermidis.

The objective of this study was to analyze quantitatively whether Weissella cibaria could affect the proliferation of five periodontopathic bacteria, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum, after incubation for 8~48 h. In addition, by using real-time PCR with a dual-labeled probe, each growth of bacteria was examined under different growth media conditions. The proliferation of periodontopathic bacteria was significantly inhibited by W. cibaria after incubation for 24~48 h (p ＜ 0.05), whereas the growth of W. cibaria was not affected by these pathogenic bacteria. The growth of P. gingivalis, T. forsythia and T. denticola significantly increased in each growth media after incubation for 24 h (p ＜ 0.05), as compared to the culture in mixed growth media. However, no differences in the growth of five periodontopathic bacteria were observed between each growth media and mixed media after incubation for 48 h. The growth and pH of W. cibaria culture significantly were changed in MRS after incubation for 24~48 h (p ＜ 0.05), as compared to the bacterial culture in mixed growth media. The pH of P. gingivalis and F. nucleatum culture significantly was changed in both growth media and mixed media after incubation for 24~48 h (p ＜ 0.05). Our data indicate that W. cibaria significantly inhibits the proliferation of five periodontopathic bacteria and each growth of bacteria is quantitatively analyzed under various media conditions by real-time PCR.

We studied the effects of herpes simplex virus type 1 (HSV-1) inoculation and topical 7,12-dimethylbenz[a]anthracene (DMBA) application, alone or in combination, on the carcinogenesis and on the amplification and expression of various cellular proto-oncogenes in hamster buccal pouch tissue. Topical DMBA treatment produced tumor formation in pouches, but HSV-1 inoculation, alone caused no neoplastic changes. In pouch tissues receiving both DMBA application and HSV-1 inoculation, the development of initial leukoplakia and tumor has hastened and enhanced in comparison with those receiving DMBA alone. Topical DMBA application to pouch tissue induced an amplification and an increase in the expression of cellular erb-B-1 (c-erb-B-1) proto-oncogene in the epithelial tissue, whereas repeated infection with HSV-1 alone did not. Topical DMBA combined with HSV-1 inoculation, however, resulted in greater amplification and expression of c-erb-B-1 proto-oncogene in the pouch epithelial tissue compared to the DMBA alone. These data indicate that HSV-1 inoculation significantly increases the carcinogenic activity of DMBA, in part, by probably enhancing DMBA-induced amplification and expression of c-erb-B-1 proto-oncogene in hamster buccal pouch tissue.