Anticancer Activity of Astaxanthin-Incorporated Chitosan Nanoparticles.

Astaxanthin (AST)-encapsulated nanoparticles were fabricated using glycol chitosan (Chito) through electrostatic interaction (abbreviated as ChitoAST) to solve the aqueous solubility of astaxanthin and improve its biological activity. AST was dissolved in organic solvents and then mixed with chitosan solution, followed by a dialysis procedure. All formulations of ChitoAST nanoparticles showed small diameters (less than 400 nm) with monomodal distributions. Analysis with Fourier transform infrared (FT-IR) spectroscopy confirmed the specific peaks of AST and Chito. Furthermore, ChitoAST nanoparticles were formed through electrostatic interactions between Chito and AST. In addition, ChitoAST nanoparticles showed superior antioxidant activity, as good as AST itself; the half maximal radical scavenging concentrations (RC50) of AST and ChitoAST nanoparticles were 11.8 and 29.3 µg/mL, respectively. In vitro, AST and ChitoAST nanoparticles at 10 and 20 µg/mL properly inhibited the production of intracellular reactive oxygen species (ROSs), nitric oxide (NO), and inducible nitric oxide synthase (iNOS). ChitoAST nanoparticles had no significant cytotoxicity against RAW264.7 cells or B16F10 melanoma cells, whereas AST and ChitoAST nanoparticles inhibited the growth of cancer cells. Furthermore, AST itself and ChitoAST nanoparticles (20 µg/mL) efficiently inhibited the migration of cancer cells in a wound healing assay. An in vivo study using mice and a pulmonary metastasis model showed that ChitoAST nanoparticles were efficiently delivered to a lung with B16F10 cell metastasis; i.e., fluorescence intensity in the lung was significantly higher than in other organs. We suggest that ChitoAST nanoparticles are promising candidates for antioxidative and anticancer therapies of B16F10 cells.

Roles of Mis18α in epigenetic regulation of centromeric chromatin and CENP-A loading.

The Mis18 complex has been identified as a critical factor for the centromeric localization of a histone H3 variant, centromeric protein A (CENP-A), which is responsible for the specification of centromere identity in the chromosome. However, the functional role of Mis18 complex is largely unknown. Here, we generated Mis18α conditional knockout mice and found that Mis18α deficiency resulted in lethality at early embryonic stage with severe defects in chromosome segregation caused by mislocalization of CENP-A. Further, we demonstrate Mis18α's crucial role for epigenetic regulation of centromeric chromatin by reinforcing centromeric localization of DNMT3A/3B. Mis18α interacts with DNMT3A/3B, and this interaction is critical for maintaining DNA methylation and hence regulating epigenetic states of centromeric chromatin. Mis18α deficiency led to reduced DNA methylation, altered histone modifications, and uncontrolled noncoding transcripts in centromere region by decreased DNMT3A/3B enrichment. Together, our findings uncover the functional mechanism of Mis18α and its pivotal role in mammalian cell cycle.

Von Hippel-Lindau gene product directs cytokinesis: a new tumor suppressor function.

One of the mechanisms of tumorigenesis is that the failure of cell division results in genetically unstable, multinucleated cells. Here we show that pVHL, a tumor suppressor protein that has been implicated in the pathogenesis of renal cell carcinoma (RCC), plays an important role in regulation of cytokinesis. We found that pVHL-deficient RCC 786-O cells were multinucleated and polyploid. Reintroduction of wild-type pVHL into these cells rescued the diploid cell population, whereas the mutant pVHL-K171G failed to do so. We demonstrate that lysine 171 of pVHL is important for the final step of cytokinesis: the midbody abscission. The pVHL-K171G caused failure to localize the ESCRT-1 interacting protein Alix and the v-SNARE complex component Endobrevin to the midbody in 786-O cells, leading to defective cytokinesis. Moreover, SUMOylation of pVHL at lysine 171 might modulate its function as a cytokinesis regulator. pVHL tumor suppressor function was also disrupted by the K171G mutation, as evidenced by the xenograft tumor formation when 786-O clones expressing pVHL-K171G were injected into mice. Most RCC cell lines show a polyploid chromosome complement and consistent heterogeneity in chromosome number. Thus, this study offers a way to explain the chromosome instability in RCC and reveals a new direction for the tumor suppressor function of pVHL, which is independent of its E3 ubiquitin ligase activity.

Acceleration time-to-ejection time ratio in fetal pulmonary artery predicts the development of neonatal respiratory distress syndrome: a prospective cohort study.

OBJECTIVE: This study investigates whether fetal pulmonary artery Doppler waveforms can predict the subsequent development of respiratory distress syndrome (RDS). STUDY DESIGN: A prospective cohort study was performed in women with impending preterm birth. Pulsatility index, resistance index, systolic-to-diastolic ratio, peak systolic velocity, and acceleration time-to-ejection time (At/Et) ratio were measured in the main pulmonary artery of fetus just before delivery. RESULTS: Neonates who developed RDS (n = 11) had significantly lower gestational age at birth than those without RDS (n = 31; median: 28.7 [range: 24.7 to 34.9] versus 32.9 [range: 25.7 to 36.0] weeks; p = 0.003); there was no difference in antenatal corticosteroid administration. Pulmonary artery At/Et ratio was significantly higher in fetuses that developed RDS compared with those that did not (median: 0.37 [range: 0.26 to 0.41] versus median: 0.30 [range: 0.21 to 0.44]; p = 0.008). RDS prediction score (=a hundredfold At/Et ratio) is significantly associated with the subsequent development of RDS after controlling for gestational age by logistic regression analysis (odds ratio = 1.31, 95% confidence interval 1.05 to 1.63, p = 0.017). CONCLUSION: An elevated At/Et ratio in the fetal pulmonary artery is independently associated with the development of RDS in preterm infants. These data suggest that fetal pulmonary artery Doppler velocimetry may provide a reliable noninvasive technique to evaluate fetal lung maturity, similar to the way in which middle cerebral artery Doppler has replaced amniocentesis for the assessment of fetal anemia.

Clinical efficacy of herbal extracts in treatment of mild to moderate acne vulgaris: an 8-week, double-blinded, randomized, controlled trial.

BACKGROUND: Herbal extracts with fewer adverse effects can be an alternative to these drugs because they can target various molecular pathways of acne pathogenesis. OBJECTIVES: To evaluate the clinical efficacy of herbal extracts (mangosteen, Lithospermum officinale, Tribulus terrestris L., Houttuynia cordata Thunb) for the treatment of mild to moderate acne vulgaris. METHODS: Sixty patients were randomized in a 1:1 ratio to receive blinded treatment with herbal extracts or vehicle for 8 weeks. Inflammatory and non-inflammatory acne lesion counts, Investigator's Global Assessment, patient's satisfaction and safety profiles were assessed. We also performed skin biopsy at baseline and week 8 to confirm immunological changes with immunohistochemistry staining. RESULTS: By the end of the study period, both inflammatory and non-inflammatory acne lesion counts were significantly decreased in herbal extracts group (p< .05). In immunohistochemistry staining, expressions of IL-1α, IL-8, and keratin 16 were significantly decreased in herbal extracts group compared to vehicle group from baseline to week 8. There was no serious adverse events in both groups. CONCLUSIONS: This herbal extracts can be a new therapeutic option for patients with mild to moderate acne vulgaris who are reluctant to use drugs.

Antibacterial Activity of Propolis-Embedded Zeolite Nanocomposites for Implant Application.

This study investigates the potential of propolis-embedded zeolite nanocomposites for dental implant application. Propolis-embedded zeolite nanocomposites were fabricated by complexation of propolis and zeolites. Then, they were pelleted with Poly(L-lactide) (PLA)/poly(ε-caprolactone) (PCL) polymer for the fabrication of a dental implant. The chemical properties of propolis were not changed during the fabrication of propolis-embedded zeolite nanocomposites in attenuated total reflection-fourier transform infra-red (ATR FT-IR) spectroscopy measurements. Propolis was continuously released from propolis-embedded zeolite nanocomposites over one month. PLA/PCL pellets containing propolis-embedded zeolite nanocomposites showed longer sustained release behavior compared to propolis-embedded zeolite nanocomposites. Propolis-embedded zeolite nanocomposite powder showed similar antibacterial activity against C. albicans in an agar plate and formed an inhibition zone as well as chlorohexidine (CHX) powder. Eluted propolis solution from PLA/PCL pellets also maintained antibacterial activity as well as CHX solution. Furthermore, eluted propolis solution from PLA/PCL pellets showed significant antibacterial efficacy against C. albicans, S. mutans and S. sobrinus. Dental implants fabricated from PLA/PCl polymer and propolis-embedded zeolite nanocomposites also have antibacterial efficacy and negligible cytotoxicity against normal cells. We suggest that PLA/PCl pellets containing propolis-embedded zeolite nanocomposites are promising candidates for dental implants.

Reactive oxygen species-sensitive nanophotosensitizers of aminophenyl boronic acid pinacol ester conjugated chitosan-g-methoxy poly(ethylene glycol) copolymer for photodynamic treatment of cancer.

The aim of this study is to prepare reactive oxygen species (ROS)-sensitive nanophotosensitizers for targeted delivery of chlorin e6 (Ce6) and photodynamic tumor therapy. For this purpose, thiodipropionic acid (TDPA) was conjugated with phenyl boronic acid pinacol ester (PBAP) (TDPA-PBAP conjugates) and then the TDPA-PBAP conjugates were attached to the chitosan backbone of chitosan-g-methoxy poly(ethylene glycol) (ChitoPEG) copolymer (ChitoPEG-PBAP). Ce6-incorporated ChitoPEG-PBAP nanophotosensitizers have an ROS-sensitive manner in vitro. The size of ChitoPEG-PBAP nanoparticles increased or disintegrated in a responsive manner against H2O2 concentration. The Ce6 release rate from ChitoPEG-PBAP nanophotosensitizers also increased by adding H2O2. These results indicated that nanophotosensitizers have sensitivity against ROS and showed triggered Ce6 release behavior. ChitoPEG-PBAP nanophotosensitizers can be more efficiently internalized into cancer cells compared to Ce6 alone and then produce ROS in a more efficient manner. Furthermore, ChitoPEG-PBAP nanophotosensitizers suppressed the viability of cancer cells in vitro and tumor growth in vivo with higher efficacy compared to Ce6 alone. Furthermore, ChitoPEG-PBAP nanophotosensitizers were efficiently delivered to irradiated tumor tissues, indicating that ChitoPEG-PBAP nanophotosensitizers can be delivered to the tumor with ROS-sensitive manner. We suggest that a ChitoPEG-PBAP nanophotosensitizer is a promising candidate for photodynamic therapy of cancers.

SUMOylation of RORalpha potentiates transcriptional activation function.

SUMOylation regulates a variety of cellular processes, including control of transcriptional activities of nuclear receptors. Here, we present SUMOylation of orphan nuclear receptor, RORalpha by both SUMO-1 and SUMO-2. SUMOylation of RORalpha occurred on the 240th lysine residue at the hinge region of human protein. PIAS family members, PIASxalpha, PIAS3, and PIASy, increased SUMOylation of RORalpha, whereas SENP2 specifically removed SUMO from RORalpha. SUMOylation-defective mutant form of RORalpha exhibited decreased transcriptional activity on RORalpha-responsive promoters indicating that SUMOylation may positively regulate transcriptional function of RORalpha.

Chondroprotective effects of aqueous extract of Anthriscus sylvestris leaves on osteoarthritis in vitro and in vivo through MAPKs and NF-κB signaling inhibition.

Osteoarthritis (OA) is a common degenerative joint disease, characterized by cartilage degradation and inflammation, in the elderly population. Anthriscus sylvestris has been used in Korean traditional medicine and contains many polyphenolic compounds such as cynaroside and chlorogenic acid, which are major active components responsible for its antioxidant effect. In this study, we aimed to evaluate the chondroprotective effect of an aqueous extract of A. sylvestris leaves (AE-ASL) on OA, both in vitro and in vivo. Rat primary chondrocytes were pretreated with AE-ASL for 1 h before interleukin-1ß (20 ng/mL) stimulation. The production of nitrite, PGE2, aggrecan, and collagen type II were detected by Griess reagent and ELISAs. The mRNA levels of iNOS, COX-2, MMP-3, and MMP-13 were measured by RT-PCR. In addition, protein levels of iNOS, COX-2, MMP-3, MMP-13, ADAMTS-4, MAPKs, and NF-κB p65 subunit were measured by western blot analysis. Sulfated glycosaminoglycan (sGAGs) were detected by dimethylmethylene blue (DMMB) assay. During in vivo study, the effects of AE-ASL were evaluated for 8 weeks in a rat model of destabilization of the medial meniscus (DMM) surgery-induced OA. AE-ASL significantly inhibited expression of nitrite, iNOS, PGE2, COX-2, MMP-3, MMP-13, and ADAMTS-4 in IL-1ß-stimulated chondrocytes. Moreover, it decreased the IL-1ß-induced degradation of aggrecan, collagen type II, and proteoglycan. In addition, AE-ASL suppressed IL-1ß-induced phosphorylation of MAPKs and NF-κB p65 subunit translocation to nucleus. In vivo, AE-ASL inhibited DMM surgery-induced cartilage destruction and proteoglycan loss. Taken together, these results suggest that AE-ASL may be a potential therapeutic agent for the alleviation of OA progression.

In Vivo and In Vitro Anti-Inflammatory Effects of Aqueous Extract of Anthriscus sylvestris Leaves.

Anthriscus sylvestris (L.) Hoffm. is a common perennial herb that is widely distributed in Europe, Korea, and New Zealand. The root of A. sylvestris has been used in Korean traditional medicine as an antitussive and cough remedy. However, the physiologically active function of A. sylvestris leaves is not yet known. In this study, we evaluated the anti-inflammatory effects, as well as the underlying molecular mechanisms of an aqueous extract of A. sylvestris leaves (AE-ASL) in vitro and in vivo. Our results indicated that pretreatment with AE-ASL significantly inhibited the lipopolysaccharide (LPS)-induced secretion of nitric oxide (NO) and prostaglandin E2 in RAW264.7 cells, without showing cytotoxicity. In addition, the LPS-induced mRNA and protein expression of inducible NO synthase, cyclooxygenase-2, and inflammatory mediators such as tumor necrosis factor alpha interleukin (IL)-1ß, and IL-6 was attenuated by pretreatment with AE-ASL in a dose-dependent manner. Therefore, we investigated the activation of nuclear factor (NF)-κB, a transcription factor regulating the expression of inflammation-related genes. AE-ASL inhibited the nuclear translocation of the NF-κB p65 subunit by suppressing the phosphorylation and degradation of the inhibitor of NF-κB (IκBα). Further, AE-ASL inhibited the LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) in RAW264.7 cells. Orally administered AE-ASL (50, 100, and 200 mg/kg of body weight [BW]) suppressed the development of carrageenan-induced rat paw edema by 15%, 31%, and 40%, respectively, after 4 h. Altogether, our results suggest that AE-ASL possesses anti-inflammatory activity, based on the suppression of NF-κB and MAPK pathways in vitro and inhibition of the carrageenan-induced paw edema in vivo.

Dual mechanisms of green tea extract (EGCG)-induced cell survival in human epidermal keratinocytes.

Beneficial effects attributed to green tea, such as its anticancer and antioxidant properties, may be mediated by (-)-epigallocatechin-3-gallate (EGCG). In this study, the effects of EGCG on cell proliferation and UV-induced apoptosis were investigated in normal epidermal keratinocytes. When topically applied to aged human skin, EGCG stimulated the proliferation of epidermal keratinocytes, which increased the epidermal thickness. In addition, this topical application also inhibited the UV-induced apoptosis of epidermal keratinocytes. EGCG was found to increase the phosphorylation of Bad protein at the Ser112 and Ser136. Moreover, EGCG-induced Erk phosphorylation was found to be critical for the phosphorylation of Ser112 in Bad protein, and the EGCG-induced activation of the Akt pathway was found to be involved in the phosphorylation of Ser136. Furthermore, EGCG increased Bcl-2 expression but decreased Bax expression, causing an increase in the Bcl-2-to-Bax ratio. In addition, we demonstrate the differential growth inhibitory effects of EGCG on cancer cells. In conclusion, this study demonstrates that EGCG promotes keratinocyte survival and inhibits the UV-induced apoptosis via two mechanisms: by phosphorylating Ser112 and Ser136 of Bad protein through Erk and Akt pathways, respectively, and by increasing the Bcl-2-to-Bax ratio. Moreover, these two proposed mechanisms of EGCG-induced cell proliferation may differ kinetically to promote keratinocyte survival.

Do patients with acne need cognitive behavioral therapy? An analysis of patient knowledge and behavior.

BACKGROUND: Acne is a common skin condition that affects adolescents as well as young adults, and numerous treatment modalities have been introduced with various success. However, most of the therapeutic measures have failed to show a long-lasting effect because acne is a multi-factorial disease. Some of the factors can be effectively modified by patients themselves. We hereby present an analysis of patients' cognition of the disease and behavioral patterns that can influence patient compliance and the efficacy of the adjacent therapy. METHODS: The survey was conducted on 136 Korean patients at a private cosmetic clinic, using a questionnaire form on their cognition and everyday habitual care. RESULTS: The results showed that the patients neither possess the proper knowledge nor behave appropriately when taking care of acne-prone skin. CONCLUSIONS: For a successful therapeutic alliance, it seems useful to provide knowledge and introduce a cognitive-behavioral therapy to the field of acne treatment.

The effects of heating and cooling on ultraviolet radiation-induced erythema and pigmentation in human skin.

BACKGROUND/PURPOSE: As most biochemical systems are affected by temperature, thermal changes before or after ultraviolet (UV) irradiation could influence skin vascular blood flow changes and inflammatory responses. In this study, our aim was to investigate the influence of thermal changes on UV-induced acute skin reactions, namely, erythema and pigmentation. METHODS: Our volunteers consisted of 10 males, with ages ranging from 22 to 24 years and with Fitzpatrick's skin type III or IV. Skin temperatures were changed with a 45 degrees C heating pad or by ice pack application before or after UV irradiation (control, 1 minimal erythema dose (MED), 2 MED) and then changes in erythema and pigmentation were measured by a Minolta Spectrophotometer CM-2002. RESULTS: The present study demonstrates that both heating and cooling increase skin erythema and reduce pigmentation, and that the timing of heating and cooling influences the UV-induced skin reaction. Pre-heating and post-cooling groups showed more UV-induced erythema than the post-heating and pre-cooling groups, respectively. CONCLUSION: Our results indicate that alteration of skin surface temperature could modulate UV-induced erythema and pigmentation responses.

Effect of pregnancy and menopause on facial wrinkling in women.

Women appear to be at greater risk of developing wrinkles with age than men. To evaluate the effect of pregnancy and menopause on facial wrinkling, a total of 186 Korean women volunteers aged between 20 and 89 years were interviewed for information on menstrual and reproductive factors. An 8-point photographic scale developed for assessing the severity of wrinkles in Asian skin was used. Cumulative sun exposure, both occupational and recreational, was estimated. In Korean women, the risk of facial wrinkling increases significantly with increasing number of full-term pregnancies (OR = 1.835, 95% confidence interval (CI) 1.017-3.314) and menopausal age (number of years since menopause) (OR = 3.909, 95% CI 1.071-14.275), while hormone replacement therapy is associated with a significantly lower risk for the development of facial wrinkling in postmenopausal women (OR = 0.221, 95% CI 0.047-0.949). Hypo-oestrogenism may play a part in the decrease of skin collagen leading to skin wrinkling in postmenopausal women.

Percutaneous intervention of spontaneous renal artery dissection complicated with renal infarction: a case report and literature review.

Spontaneous renal artery dissection (SRAD) is a rare condition that occurs before renal infarction. Using percutaneous intervention to treat SRAD remains controversial because it is not clear whether it is feasible or effective. We describe a 48-year-old male patient with SRAD complicated with renal infarction who was successfully treated with percutnaeous angioplasty and renal artery stenting.