Byeng Chul Yu

Fucoidan inhibits UVB-induced MMP-1 promoter expression and down regulation of type I procollagen synthesis in human skin fibroblasts

UVB reduces type I procollagen levels and increases matrix metalloproteinases-1 (MMP-1) levels in human skin and plays a major role in the process of photoaging. We previously reported that fucoidan inhibits UVB-induced MMP-1 expression at the protein and mRNA levels in human skin fibroblasts (HS68). Yet, the effects of fucoidan on UVB-induced MMP-1 promoter activity and type I procollagen have not been investigated. In this study, we assessed the effects of fucoidan on the inhibition of MMP-1 promoter activity and on the increase of type I procollagen synthesis in human skin fibroblasts. Fucoidan treatment significantly inhibited MMP-1 promoter activity compared to UVB irradiation alone. Fucoidan treatment also increased type I procollagen mRNA and protein expression in a dose-dependent manner compared to the control. Our data indicate that fucoidan may prevent UVB-induced MMP-1 expression and inhibit down-regulation of type I procollagen synthesis. We suggest that fucoidan may be a potential therapeutic agent to prevent and treat skin photoaging.

Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells.

Abstract Context: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown. Objective: The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells in vitro. Materials and methods: To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used. Results: CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1β (4.775 versus 0.713 pg/ml, IC50 = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC50 = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC50 = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation. Discussion and conclusion: Our results indicated that CAPE can modulate mast cell-mediated allergic disease.

Clinical features of infectious endophthalmitis in South Korea: a five-year multicenter study.

BackgroundTo investigate clinical features of infectious endophthalmitis over five years in a South Korean population.MethodsMedical records of consecutive patients diagnosed with infectious endophthalmitis at eight institutions located in Gyeongsangnam-do and Pusan city between January 1, 2004 and July 31, 2010 were reviewed.ResultsA total of 197 patients were diagnosed and treated. An average of 30.0 infectious endophthalmitis per year was developed. The annual incidence rate of postoperative endophthalmitis during 2006 ~ 2009 was 0.037%. The ratios of male to female and right to left were 50.2%: 49.8 % and 54.8%: 43.2%, respectively. Eighth decade and spring were the peak age (36.6%) and season (32.0%) to develop the infectious endophthalmitis. The most common past history in systemic disease was hypertension (40.4%), followed by diabetes (23.4%). Cataract operation (60.4%) was the most common cause, among which most of them was uneventful phacoemulsification (95.9%). Corneal laceration (51.6%) and liver abscess (42.9%) were the most common causes of traumatic and endogenous endophthalmitis, respectively. The percentages of patients with initial and final visual acuity less than counting fingers were 62.6% and 35.2%, respectively. Treatment with vitrectomy with or without intravitreal antibiotics injection was administered to 72.6% of patients, while 17.3% received intravitreal antibiotics only.ConclusionsOur study revealed that the development of infectious endophthalmitis was related with seasonal variation and increased during our study period. Pars plana vitrectomy was preferred for the treatment of infectious endophthalmitis in South Korea.

The effect of cilostazol on the expression of matrix metalloproteinase-1 and type I procollagen in ultraviolet-irradiated human dermal fibroblasts

AIM Cilostazol is a selective inhibitor of type III phosphodiesterase that inhibits platelet aggregation. Cilostazol is a useful vasodilator, antithrombotic, and cardiotonic agent. Ultraviolet B (UVB) irradiation increases the production of matrix metalloproteinase-1 (MMP-1) during skin photoaging. The UVB-induced increase of MMP-1 results in connective tissue damage, and the skin becomes wrinkled and aged. Here, we investigated the capacity of cilostazol to inhibit MMP-1 expression in UVB-irradiated human dermal fibroblasts. MAIN METHODS Cultured human dermal fibroblasts were irradiated with UVB, followed by the addition of cilostazol to the culture medium. KEY FINDINGS Post-treatment with cilostazol attenuated UVB-induced production of MMP-1 and prevented the reduction of type I procollagen. Cilostazol inhibited UVB irradiation-induced phosphorylation of the mitogen-activated protein kinase (MAPK) signaling molecules Jun-N-terminal kinase (JNK) and p38 kinase, as well as activator protein-1 (AP-1) in dermal fibroblasts. SIGNIFICANCE Overall, these results demonstrate that cilostazol regulates UVB-induced MMP-1 expression and type I procollagen synthesis by inhibiting MAPK signaling and AP-1 activity. Therefore, we suggest that cilostazol may be useful for the prevention and treatment of skin photodamage caused by UVB-irradiation.

The Prevalence of High Myopia in 19 Year-Old Men in Busan, Ulsan and Gyeongsangnam-Do

OBJECTIVES The purpose of this study was to estimate the prevalence and correlated factors of high myopia in 19 year-old men in Southeast Korea. METHODS This retrospective study was based on the medical checkup data of conscription during 2005. The study subjects were 19 years old men in Busan, Ulsan and Gyeongsangnam-do. The health checkup data of the conscripts consisted of noncycloplegic autorefraction test, the biometric data and social factors. To analyze the social and biometric effects, we classified the biometric factors into 4 or 5 groups and the social factors into 3 groups. High myopia was defined as a spherical equivalent of under -6.0 diopter. Data analysis was performed using the chi square test for trends and multiple logistic regression analysis. The SAS (version 9.1) program was used for all the analyses. RESULTS The prevalence of high myopia was 12.39% (6256 /50,508). The factors correlated with high myopia were the residence area (OR, 2.07; 95% CI, 1.77 to 2.4 for small city; OR, 2.01; 95% CI, 1.72 to 2.34 for metropolis; the reference group was rural area), academic achievement (OR, 1.43; 95% CI, 1.34 to 1.53 for students of 4-and 6-year-course university; the reference group was high school graduates & under) and blood pressure (OR, 1.54; 95% CI, 1.10 to 2.16 for hypertension; OR, 1.09; 95% CI, 1.02 to 1.17 for prehypertension; OR, 1.10; 95% CI, 1.01 to 1.20 for hypotension; the reference group was normal blood pressure). CONCLUSIONS More than one tenth of the young men were high myopia as one of the risk factor for visual loss. Further studies on high myopia and its complications are needed to improve eye health in Southeast Korea.

Attenuation of IFN-γ-induced B7-H1 expression by 15-deoxy-delta12,14-prostaglandin J2 via downregulation of the Jak/STAT/IRF-1 signaling pathway

AIM B7-H1, which belongs to the B7 family of costimulatory molecules, is implicated in the ability of tumors to evade the host immune response. The development of evasion mechanisms within the tumor microenvironment may be responsible for poor therapeutic responses. In this manuscript, we report that the 15-deoxy-δ(12,14)-prostaglandin J2 (15d-PGJ2), peroxisome proliferator-activated receptor gamma (PPARγ) activator leads to the downregulation of the cancer-associated expression of B7-H1 in response to interferon-gamma (IFN-γ) and the associated signaling cascades. MAIN METHODS The expression of B7-H1 from IFN-γ-induced B16F10 melanoma cells was measured with flow cytometric analysis. The regulatory mechanisms of 15d-PGJ2 on cellular signaling pathways were examined using Western blot and electrophoretic mobility shift assays. KEY FINDINGS The flow cytometric analysis revealed that the B7-H1 costimulatory molecule is significantly upregulated in B16F10 melanoma cells by stimulation with IFN-γ. However, 15d-PGJ2 strongly downregulates B7-H1 expression in IFN-γ-stimulated B16F10 melanoma cells. Furthermore, the significant damping effect of 15d-PGJ2 on B7-H1 expression involves the inhibition of the tyrosine phosphorylation of Janus kinase (Jak) and signal transducer(s) and activator(s) of transcription (STAT) and, thereby, the interferon regulatory factor-1 (IRF-1) trans-activation of STAT. These effects of 15d-PGJ2 were not abrogated by the PPARγ antagonist GW9662, indicating that they occur through a PPARγ-independent mechanism. SIGNIFICANCE In this study, we demonstrate that 15d-PGJ2 suppresses the IFN-γ-elicited expression of B7-H1 by the inhibition of IRF-1 transcription via the Jak/STAT signaling pathway through a PPARγ-independent mechanism in mouse melanoma cells.

NecroX-5 prevents breast cancer metastasis by AKT inhibition via reducing intracellular calcium levels

A major goal of breast cancer research is to prevent the molecular events that lead to tumour metastasis. It is well-established that both cytoplasmic and mitochondrial reactive oxygen species (ROS) play important roles in cell migration and metastasis. Accordingly, this study examined the molecular mechanisms of the anti-metastatic effects of NecroX-5, a mitochondrial ROS scavenger. NecroX-5 inhibited lung cancer metastasis by ameliorating migration in a mouse model. In human cancer cells, the inhibition of migration by NecroX-5 is cell type-dependent. We observed that the effect of NecroX-5 correlated with a reduction in mitochondrial ROS, but mitochondrial ROS reduction by MitoQ did not inhibit cell migration. NecroX-5 decreased intracellular calcium concentration by blocking Ca2+ influx, which mediated the inhibition of cell migration, AKT downregulation and the reduction of mitochondrial ROS levels. However, the reduction of mitochondrial ROS was not associated with supressed migration and AKT downregulation. Our study demonstrates the potential of NecroX-5 as an inhibitor of breast cancer metastasis.

Intraperitoneal administration of adipose tissue-derived stem cells for the rescue of retinal degeneration in a mouse model via indigenous CNTF up-regulation by IL-6

As the worlds population begins to age, retinal degeneration is an increasing problem, and various treatment modalities are being developed. However, there have been no therapies for degenerative retinal conditions that are not characterized by neovascularization. We investigated whether transplantation of mouse adipose tissue‐derived stem cells (mADSC) into the intraperitoneal space has a rescue effect on NaIO3‐induced retinal degeneration in mice. In this study, mADSC transplantation recovered visual function and preserved the retinal outer layer structure compared to the control group without any integration of mADSC into the retina. Moreover, endogenous ciliary neurotrophic factor (CNTF) was elevated in the retinas of mADSC‐treated mice. We found that lipopolysaccharide (LPS) or LPS‐stimulated monocyte supernatant induced the secretion of granulocyte colony stimulating factor (GCSF), CD54, CXCL10, interleukin‐6 (IL‐6), and CCL5 from the mADSC by cytokine array. Network inference was conducted to investigate signaling networks related to CNTF regulation. Based on bioinformatics data, the expression of IL‐6 was related to the expression of CNTF. Additionally, intravitreal injection of IL‐6 in rats produced up‐regulation of endogenous CNTF in the retina. mADSC had a rescue effect on retinal degeneration through the up‐regulation of endogenous CNTF by IL‐6. Thus, transplantation of mADSC could be a potential treatment option for retinal degeneration.

Comparison of the most common isolates of postoperative endophthalmitis in South Korea; Enterococcus species vs coagulase-negative staphylococci

BackgroundTo compare the related factors or manifestations of the two most common isolates of post-operative endophthalmitis, which were Enterococcus spp. and coagulase-negative staphylococci (CNS) in South Korea.MethodsMedical records were reviewed for cases of post-operative endophthalmitis caused by Enterococcus spp. and CNS at eight institutions between January 2004 and July 2010. Various factors including age, sex, residence, systemic diseases, smoking and drinking history, and best corrected visual acuity, and length of time between causative intraocular surgery and symptom development were compared between the two groups.ResultsThe total number of post-operative endophthalmitis cases was 128 and in 116 cases, microbiological culture tests from the aqueous humor or vitreous were performed. Among these cases, 67 (57.8%) were culture proven. Among these 67 cases, 19 (28.4%) were caused by Enterococcus spp., 14 (20.9%) were caused by Staphylococcus epidermidis endophthalmitis, and 5 (7.5%) were caused by other CNS spp. Age, sex, causative procedure, past medical history, social history, and laterality were not different in the two groups. Mean initial and final visual acuity were significantly worse in the Enterococcus spp. endophthalmitis group than in the CNS group (p = 0.049, 0.042, respectively). Length of time between the causative procedure and symptom development was significantly shorter in cases of Enterococcus spp. endophthalmitis (p = 0.004).ConclusionsEnterococcus spp. induce more severe and rapid-onset postoperative endophthalmitis than CNS. Infectious endophthalmitis developed within 2 days after cataract operation could be caused by Enterococcus spp. and have chance to be poor prognosis in South Korea.