The Molecular Mechanism of Polyphenols with Anti-Aging Activity in Aged Human Dermal Fibroblasts.

Skin is the largest organ in the body comprised of three different layers including the epidermis, dermis, and hypodermis. The dermis is mainly composed of dermal fibroblasts and extracellular matrix (ECM), such as collagen and elastin, which are strongly related to skin elasticity and firmness. Skin is continuously exposed to different kinds of environmental stimuli. For example, ultraviolet (UV) radiation, air pollutants, or smoking aggravates skin aging. These external stimuli accelerate the aging process by reactive oxygen species (ROS)-mediated signaling pathways and even cause aging-related diseases. Skin aging is characterized by elasticity loss, wrinkle formation, a reduced dermal-epidermal junction, and delayed wound healing. Thus, many studies have shown that natural polyphenol compounds can delay the aging process by regulating age-related signaling pathways in aged dermal fibroblasts. This review first highlights the relationship between aging and its related molecular mechanisms. Then, we discuss the function and underlying mechanism of various polyphenols for improving skin aging. This study may provide essential insights for developing functional cosmetics and future clinical applications.

Primary Angle-Closure Glaucoma With Normal Intraocular Pressure at the First Visit: Its Prevalence and Ocular Characteristics.

PURPOSE: To investigate the prevalence of normal intraocular pressure (IOP) at first visit among patients with primary angle-closure glaucoma (PACG) and their ocular characteristics. PATIENTS AND METHODS: We retrospectively reviewed patients with PACG in a referral center. According to untreated IOP, we divided PACG eyes into 2 groups: those with normal IOP and those with high IOP (>21 mm Hg) at the first visit. RESULTS: One hundred sixty eyes of 160 Korean PACG patients were included. Sixty percent (97/160) of the patients had normal IOP at their first visit. The PACG patients with initially normal IOP had significantly longer axial length (mean±SD, 22.99±0.76 vs. 22.74±0.61) and deeper "true" anterior chamber depth (ACD) (2.09±0.27 vs. 1.82±0.33) than those with initially high IOP (both P<0.05). Multiple logistic regression revealed that deeper "true" ACD (per 0.1 mm; odds ratio, 1.38) and more hyperopic refractive errors (odds ratio, 1.48) were independent predictors of initially normal IOP in PACG eyes (P<0.05). The prevalence of disc hemorrhage was higher in PACG patients with initially normal IOP than in those with initially high IOP (29.9% vs. 14.3%, P=0.029). CONCLUSIONS: Sixty percent of patients with PACG had normal IOP at their first visit. This suggests that without gonioscopy clinicians may misdiagnose PACG as normal tension glaucoma. ACD measurement can aid the diagnosis of PACG because even PACG eyes with initially normal IOP have shallow ACD.

Histone Demethylase Gene PHF2 Is Mutated in Gastric and Colorectal Cancers.

Alterations of genes involved in histone modification are common in cancers. A histone demethylase-encoding gene PHF2 is considered a putative tumor suppressor gene (TSG). PHF2 is essential for p53-mediated TSG functions such as chemotherapy-mediated cancer cell killing. However, inactivating mutations of PHF2 that could inactivate its functions are not reported in cancers. In a genome database, we observed that the PHF2 gene possessed mononucleotide repeats, which could be mutated in cancers with high microsatellite instability (MSI-H). For this, we analyzed 124 colorectal cancers (CRCs) and 79 gastric (GCs) cancers for the mutations and their intratumoral heterogeneity (ITH). Twenty-two of 79 CRCs (27.8 %) and 7 of 34 GCs (20.6 %) harboring MSI-H exhibited frameshift mutations. However, we found no such mutations in microsatellite stable/low MSI (MSS/MSI-L) cancers. Also, we studied ITH for the detected frameshift mutations in 16 cases of CRCs and detected ITH in two (12.5 %) cases. Our data reveal that TSG gene PHF2 harbors mutational ITH as well as the frameshift mutations in CRC and GC with MSI-H. Based on this, it is suggested that frameshift mutations of PHF2 may play a role in tumorigenesis through its TSG inactivation in CRC and GC.

Interocular symmetry of retinal nerve fibre layer thickness in healthy eyes: a spectral-domain optical coherence tomographic study.

PURPOSE: This study was performed to investigate the interocular symmetry of peripapillary retinal nerve fibre layer (RNFL) thickness, as measured by Cirrus high-definition spectral-domain optical coherence tomography (OCT), in healthy eyes. A wide range of subject ages and refractive errors was examined. METHODS: The retinal nerve fibre layer thickness was measured in 1,234 healthy eyes from 617 subjects using OCT. Interocular differences (right eye minus left eye) in global area and quadrant nerve fibre layer thicknesses were measured. The effect of age and refractive error on interocular nerve fibre layer thickness difference was also examined. RESULTS: Means (and standard deviations) of subjects' ages and average subject refractive errors were 36.4 ± 19.8 years (range: five to 80 years) and -2.67 ± 2.91 D (range: -14.13 to +5.75 D), respectively. Cutoff limits for normal interocular nerve fibre layer thickness differences (2.5th and 97.5th percentiles of normative data) in the global area and in the superior, nasal, inferior and temporal quadrants were 9.5, 23.0, 15.6, 20.0 and 22.6 µm, respectively. Mean interocular retinal nerve fibre layer thickness differences in global area and in superior, nasal, inferior and temporal quadrants were 0.7 (p < 0.001), -3.9 (p < 0.001), 2.6 (p < 0.001), 1.1 (p = 0.007) and 3.0 (p < 0.001) µm, respectively. Interocular nerve fibre layer thickness differences were not significantly correlated with age or refractive error (average of right and left eyes, both p > 0.05). CONCLUSIONS: Significant interocular differences in peripapillary retinal nerve fibre layer thickness exist in healthy eyes, particularly in the superior quadrant. This finding should be considered when comparing retinal nerve fibre layer thickness between right and left eyes.

Effect of myopia and age on optic disc margin anatomy within the parapapillary atrophy area.

PURPOSE: To evaluate the effect of myopia and age on temporal optic disc margin anatomy within the parapapillary atrophy (PPA) area by use of spectral-domain optical coherence tomography (OCT). METHODS: Fifty young myopic eyes with PPA (myopic PPA group), 50 aged non-myopic eyes with PPA (aged PPA group), and 50 young non-myopic eyes without PPA (control group) were enrolled. High-definition OCT scanning was used to obtain horizontal cross-sectional optic nerve head (ONH) images. By use of these OCT scans we investigated three temporal optic disc margin structures: the configuration of the border tissue of Elschnig; the cross-sectional ONH structure coinciding with the clinically detected optic disc margin; and the integrity of the retinal layers within the PPA area. RESULTS: The distribution of the configuration of the border tissue of Elschnig and the cross-sectional ONH structure coinciding with the clinically detected optic disc margin of the myopic PPA group differed significantly from those of the control group (P < 0.01) whereas those of the aged PPA group did not (P > 0.05). Other than the photoreceptor layer, the retinal layers within the PPA area were more commonly impaired in the myopic PPA group than in the aged PPA group (P < 0.001). CONCLUSIONS: Myopia and aging led to different structural changes in temporal optic disc margin anatomy within the PPA area. This finding implies that different mechanisms may underlie myopic and age-related PPA development.

Characteristics of patients with epilepsy who use a website providing healthcare information about epilepsy in South Korea.

We studied characteristics of epilepsy patients who use 'Epilia', a healthcare website for epilepsy patients, and the impact of 'Epilia' on patient satisfaction and attitude about epilepsy. A total of 153 epilepsy patients from 'Epilia' (online group) and 367 patients from epilepsy clinics (offline group) were recruited. A survey was done to investigate their socio-demographic, epilepsy-related, and psychological characteristics, as well as attitude alterations after beginning to use 'Epilia'. Factors affecting attitude were also identified in the online group. Online group had more severe and more frequent seizures, more adverse effects, more anxiety and depression, and worse quality of life than offline group. Online group patients who are more satisfied, who take two or more antiepileptic drugs, who visit to 'Epilia' more and longer had a greater positive attitude change than those without these characteristics. A healthcare website can contribute to self-management by providing useful information and education for epilepsy patients.

Angle closure in the Namil study in central South Korea.

OBJECTIVE: To assess the prevalence and associated risk factors of angle closure in a defined population as part of the Namil Study. METHODS: In this cross-sectional epidemiologic study for residents aged 40 years or older in Namil-myon, a rural area in central South Korea, the examination included slitlamp biomicroscopy, applanation tonometry, gonioscopy, autorefraction, fundus photography, corneal thickness measurement, visual field test with frequency-doubling technology, and anterior chamber depth (ACD) and axial length (AL) measurements with partial coherence interferometry. Standard automated field test and optical coherence tomography or scanning laser polarimetry were performed to confirm the glaucomatous visual field/optic disc damage. Angle closure included primary angle-closure suspect (PACS), primary angle closure (PAC), and primary angle-closure glaucoma (PACG). Definitions of PACS, PAC, and PACG were based on the recommendations from the International Society for Geographical &Epidemiological Ophthalmology. RESULTS: Among the 1426 individuals enrolled for the assessment, with exclusion of cataract surgery, the prevalence rates of PACS, PAC, PACG, and overall angle closure in at least 1 eye were 2.0% (95% CI, 1.3%-2.8%), 0.5% (95% CI, 0.1%-0.9%), 0.7% (95% CI, 0.3%-1.1%), and 3.2% (95% CI, 2.3%-4.2%), respectively. Multivariate analysis found that older age (odds ratio [OR], 1.8797; 95% CI, 1.4624-2.4162), shallower ACD (OR, 0.9982; 95% CI, 0.9977-0.9987), and shorter AL (OR 0.9978; 95% CI, 0.9969-0.9988) (P < .001 for each) were significantly associated with angle closure. CONCLUSIONS: The overall prevalence of angle closure was 3.2% in the present study. On the basis of these findings, increasing age, shallower ACD, and shorter AL appear to be associated with angle closure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00727168.

Age-related differences in the brain areas outside the classical language areas among adults using category decision task.

Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that similar activation patterns were found in classical language processing areas across the three age groups although regional lateralization indices in Broca's and Wernicke's areas decreased with age. The greatest differences, however, among the three groups were found primarily in the brain areas not associated with core language functioning including the hippocampus, middle frontal gyrus, ventromedial frontal cortex, medial superior parietal cortex and posterior cingulate cortex. Therefore, the non-classical language areas may exhibit an age-related difference between three age groups while the subjects show a similar activation pattern in the core, primary language processing during a semantic decision task.

Changes of the Retina and Intrinsic Survival Signals in a Rat Model of Glaucoma following Brinzolamide and Travoprost Treatments.

PURPOSE: The purpose of this study is to examine the changes of the retina and the intrinsic survival signals of the retina by brinzolamide (Azopt®) and travoprost (Travatan®) in a rat model of chronic ocular hypertension. METHODS: Chronic ocular hypertension was induced by cauterization of three episcleral veins. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) staining was performed and the expression of glial fibrillary acidic protein (GFAP) was examined to evaluate changes of retinal ganglion cell (RGC) apoptosis and glial cell activation. Western blot analyses of the bcl-2 family and extracellular signal-regulated kinases (ERK) were done to identify changes of the intrinsic survival signaling pathway in the retina. RESULTS: GFAP expression and TUNEL staining revealed significant decreases in RGC apoptosis and glial cell activation after brinzolamide and travoprost administration; bcl-2 and bcl-xL expression were significantly increased after intraocular pressure elevation and it was further increased with brinzolamide and travoprost treatment. This enhancement of survival signaling may have contributed to the decrease in RGC apoptosis. However, the role of ERK signaling was not significant. CONCLUSIONS: Decrease in retinal damage and increased intrinsic survival signals suggests the neuroprotective potential of brinzolamide and travoprost in an animal model of chronic ocular hypertension, but further studies are required.

The reliability and validity of the Korean version of the Epworth sleepiness scale.

OBJECTIVE: The Epworth sleepiness scale (ESS) is widely used to measure the subject's average sleep propensity across those different situations in daily life, particularly in patients with sleep-disordered breathing. The purposes of this study were to test the hypothesis that the Korean version of the ESS (KESS) is valid and evaluate its usefulness. MATERIALS AND METHODS: We developed the KESS, which involved translating into Korean and then translating back into English to check its accuracy. A total of 273 participants (181 obstructive sleep apnea (OSA)-37 mild, 61 moderate, 83 severe, 32 simple snoring and 60 normal) were included in this study. All subjects completed the overnight polysomnograph and 53 of the total subjects were randomly selected for a retest with the questionnaire approximately 2∼4 weeks later. The associations between KESS and the degree of OSA were examined through ANCOVA, adjusted for age, sex and BMI. RESULTS: The total score and each item's score of KESS in patients with OSA were significantly higher than subjects with normal controls (p < 0.01). As the severity of OSA increased, the KESS showed significantly increasing patterns (p for trend <0.01). The KESS in patient groups showed good internal consistency (Cronbach's α = 0.90) and test-retest reliability (r = 0.78 to 0.93). CONCLUSION: The KESS is a reliable and valid tool for screening patients with daytime sleepiness in Korea.

Quantitative analysis of retinal nerve fiber layer thickness of normal children and adolescents.

PURPOSE: To determine the normal range of retinal nerve fiber layer (RNFL) thickness of normal children and adolescents by optical coherence tomography (OCT). METHODS: This study analyzed 144 eyes of 72 normal children and adolescents by OCTIII (Zeiss-Humphrey, San Leandro, CA., USA) and the results were compared with the RNFL thickness of Korean adults. RESULTS: The mean RNFL thickness of the 72 normal children and adolescents was 105.53 +/- 10.33 microm. The mean values for left and right eyes were 104.28 +/- 7.68 microm and 106.79 +/- 12.98 microm, respectively. There was no significant difference in mean RNFL thickness between the 4 quadrants of the left and right eyes (p=0.926). Additionally, the mean RNFL thickness showed a similar size pattern regardless of age (p=0.99). RNFL thickness was found to be greater in adults than in children or adolescents, although the difference was not statistically significant (p=0.295). Likewise, no significant difference was found with gender (p=0.822) or in the pattern of RNFL thickness of 12 sectors between children and adults (p=0.08). CONCLUSIONS: This study reports RNFL thickness, as determined by OCT, for normal children and adolescents. We found this measurement method to be suitable for the early diagnosis of glaucoma and to the examination of its progression in these subjects. The findings could be used as clinical parameters for adolescent glaucoma.

The effects of glucose on the expression of MMP and TIMP in cultured retinal pigment epithelial cells.

This study evaluated the effects of glucose in human retinal pigment epithelial (RPE) cells to investigate the cause of diabetic retinal complications. Human RPE cells were cultured in media containing 5.5 mM, 11.0 mM, and 16.5 mM D-glucose. The present study performed proliferation and migration assays, and conducted western blotting for the protein expression, as well as RT-PCR for the mRNA expression, of MMP-2 and -9, and TIMP-1 and -2. The results of the western blotting analysis showed that increasing glucose concentration significantly increased the expression of MMP-2 and -9, but significantly decreased the expression of TIMP-1 and -2. Moreover, the RT-PCR results indicated significant increases in the mRNA expression of MMP-2 and -9, as well as of TIMP-1 and -2, by raising glucose concentration. This study provides fundamental data for future research on the mechanism of retinal complication in diabetic patients.