Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric Cancer.

BACKGROUND: Gastric cancer, one of the leading causes of cancer-related death, is strongly associated with H. pylori infection, although other risk factors have been identified. The sirtuin (Sirt) family is involved in the tumorigenesis of gastric cancer, and sirtuins can have pro- or anti-tumorigenic effects. METHODS: After determining the overall survival rate of gastric cancer patients with or without Sirt6 expression, the effect of Sirt6 upregulation was also tested using a xenograft mouse model. The regulation of Sirt6 and Sirt1, leading to the induction of mouse double minute 2 homolog (MDM2) and reactive oxygen species (ROS), was mainly analyzed using Western blotting and immunofluorescence staining, and gastric cancer cell (SNU-638) death associated with these proteins was measured using flow cytometric analysis. RESULTS: Sirt6 overexpression led to Sirt1 suppression in gastric cancer cells, resulting in a higher level of gastric cancer cell death in vitro and a reduced tumor volume. ROS and MDM2 expression levels were upregulated by Sirt6 overexpression and/or Sirt1 suppression according to Western blot analysis. The upregulated ROS ultimately led to gastric cancer cell death as determined via Western blot and flow cytometric analysis. CONCLUSION: We found that the upregulation of Sirt6 suppressed Sirt1, and Sirt6- and Sirt1-induced gastric cancer cell death was mediated by ROS production. These findings highlight the potential of Sirt6 and Sirt1 as therapeutic targets for treating gastric cancer.

Corneal epithelial remodeling induced by combined small incision lenticule extraction and accelerated corneal collagen crosslinking for myopia

PURPOSE: To evaluate the changes of the corneal epithelial thickness (ET) profile induced by combined small incision lenticule extraction and accelerated corneal collagen crosslinking (SMILE-xtra) for myopia compared with the standard small incision lenticule extraction (SMILE). SETTING: Nuri Eye Hospital, 61, Dunsan-ro, Seo-gu, Daejeon, 35233, Korea. DESIGN: Retrospective cross-sectional study. METHODS: Thirty-one myopic eye undergoing SMILE-xtra and control group of 36 myopic eyes undergoing SMILE were retrospectively analyzed. Spectral-domain optical coherence tomography (CIRRUS™ HD-OCT 5000, ZEISS, Dublin, CA) was used to measure corneal ET of 17 zones within the central 7-mm zone at preoperative, postoperative 1 month, 3 months and 6 months. Postoperative ET alterations were analyzed for correlation with treatment parameters. RESULTS: There was no difference in preoperative mean age, postoperative MRSE, visual acuity, and ablation depth between the two groups, and there was a significant difference in preoperative central corneal thickness. Both groups showed the greatest increase in corneal ET in the paracentral area on the inferotemporal area, respectively, for 6 months. The preoperative MRSE and the ablation depth showed significant correlation with the postoperative epithelial thickening in mid-peripheral sectors in both groups, and significant negative correlations in paracentral sectors only in SMILE-xtra group. CONCLUSIONS: It is significant as the first study to compare corneal epithelial remodeling between SMILE and SMILE with accelerated corneal collagen crosslinking. The SMILE-xtra with the relatively large corneal ablation did not show a significant difference in the pattern of corneal epithelial remodeling compared to the SMILE group.

Diagnostic Validation of the Screening Corneal Objective Risk of Ectasia Analyzer Evaluated by Swept Source Optical Coherence Tomography for Keratoconus in an Asian Population.

We aimed to investigate the diagnostic accuracy of Screening Corneal Objective Risk of Ectasia (SCORE) Analyzer software using ANTERION, a swept-source optical coherence tomography device, for keratoconus diagnosis in an Asian population. A total of 151 eyes of 151 patients were included in this retrospective study as follows: 60, 45, and 46 keratoconus, keratoconus suspects, and normal control eyes, respectively. Parameters in the SCORE calculation, including six indices, were compared for the three groups. The receiver operating characteristic curve analysis and cut-off value were estimated to assess the diagnostic ability to differentiate keratoconus and keratoconus suspect eyes from the normal group. The SCORE value and six indices were significantly correlated-"AntK max" (R = 0.864), "AntK oppoK" (R = 0.866), "Ant inf supK" (R = 0.943), "Ant irre 3mm" (R = 0.741), "post elevation at the thinnest point" (R = 0.943), and "minimum corneal thickness" (R = -0.750). The SCORE value showed high explanatory power (98.1%), sensitivity of 81.9%, and specificity of 78.3% (cut-off value: 0.25) in diagnosing normal eyes from the keratoconus suspect and keratoconus eyes. The SCORE Analyzer was found to be valid and consistent, showing good sensitivity and specificity for keratoconus detection in an Asian population.

Near-surface termination of upward-propagating strike-slip ruptures on the Yangsan Fault, Korea.

We present a new example of the termination of strike-slip paleoearthquake ruptures in near-surface regions on the Yangsan Fault, Korea, based on multi-scale structural observations. Paleoearthquake ruptures occur mostly along the boundary between the inherited fault core and damage zone (N10-20°E/> 75°SE). The ruptures propagated upward to the shallow subsurface along a < 3-cm-wide specific slip zone with dextral-slip sense, along which the deformation mechanism is characterized mainly by granular flow in near-surface region. The ruptures either reach the surface or are terminated in unconsolidated sediment below the surface. In the latter case, the rupture splays show westward bifurcation, and their geometry and kinematics show a change to NNW-strike with low-angle dip and dextral-reverse oblique-slip sense in the strata. We suggest that the upward termination of the contractional strike-slip ruptures is controlled by the inherited fault geometry that is unfavorable with respect to the stress field (ENE-WSW σHmax) at basement depths in terms of movement on the fault, and the lack of extension of the fault into shallow subsurface; a depth-dependent change in stress from σHmax > σv > σHmin to σHmax > σHmin > σv at depth of a ~ 200 m; and the physical properties of unconsolidated sediment, which have low inter-granular cohesion, resulting in distributed deformation.

Anterior segment characteristics in normal and keratoconus eyes evaluated with a new type of swept-source optical coherence tomography.

PURPOSE: This study aimed to evaluate and compare the discriminating ability of corneal elevation maps generated using a swept-source optical coherence tomography (SS-OCT) (SS-OCT ANTERION, Heidelberg Engineering, Heidelberg, Germany), which was estimated with different reference surfaces, to distinguish normal corneas from those with keratoconus and keratoconus suspect. METHODS: A total of 126 eyes of patients, which comprised 43, 37, and 46 keratoconus, keratoconus suspects, and normal controls, respectively, were included in this study. The anterior and posterior elevations at the thinnest point under the best-fit sphere (BFS) and toric-ellipsoid (BFT), respectively, and other corneal parameters were measured using the SS-OCT. In addition, the receiver operating characteristic (ROC) curve analysis and cut-off value were calculated to evaluate the diagnostic ability of the corneal elevation values in differentiating keratoconus and keratoconus suspects from normal eyes. RESULTS: The mean total keratometric and corneal elevation values were significantly higher in the keratoconus group than in the other groups. Pachymetric parameters exhibited the lowest values for keratoconus. In addition, ROC curve analyses showed a high accuracy of the thinnest point anterior and posterior BFT for both keratoconus and keratoconus suspects and normal controls (area under the ROC were 0.969 and 0.961, respectively). Furthermore, the optimal cut-off point of the posterior elevation at the thinnest point under BFT was 16.44 µm (sensitivity and specificity of 86% and 98%, respectively) for differentiating keratoconus from normal and keratoconus suspect eyes. CONCLUSIONS: The elevation map using the BFS and BFT references measured with the anterior segment SS-OCT is considered an effective indicator for keratoconus diagnosis. Therefore, the anterior segment SS-OCT can effectively differentiate keratoconus from suspected keratoconus and normal corneas by measuring parameters such as posterior and anterior elevations, pachymetry, and keratometry.

Effect of preoperative keratometry on visual outcomes after small-incision lenticule extraction for myopia.

PURPOSE: To investigate the relationship between preoperative keratometry (K) and postoperative refraction and compare the visual outcomes after small-incision lenticule extraction (SMILE) between preoperative flat and steep corneas. METHODS: This study involved 814 consecutive eyes of 409 patients who underwent SMILE. A month later, a linear regression analysis of the relationship between preoperative K and the residual spherical equivalent (SE) along with eyes divided by a single standard deviation between flat and steep corneas (< 41.85 D, > 44.57 D, respectively) was conducted. Eyes were distinguished based on the degree of myopia. RESULTS: One month after surgery, no significant correlation existed between mean preoperative K and residual SE (P = 0.459). Linear regression analysis showed a weak negative correlation between flat corneas (r2 = 0.042, P = 0.025) rather than steep corneas (P = 0.908). Eyes with preoperative low myopia (< 3.00 D) (r2 = 0.233, P = 0.001) had a weak correlation compared with moderate and high myopia (P = 0.272, P = 0.257, respectively). Twelve months later, the predictability, safety, and efficacy did not vary between preoperative flat and steep corneas (P > 0.05). CONCLUSIONS: One month after SMILE for myopia, the corneas were flatter in the preoperative flat corneas or all the low myopic corneas, and they were more overcorrected. However, preoperative corneal curvature does not influence visual outcomes at 1 year after SMILE.

Visual Outcomes After SMILE, LASEK, and LASEK Combined With Corneal Collagen Cross-Linking for High Myopic Correction.

PURPOSE: To compare the visual and refractive outcomes of small-incision lenticule extraction (SMILE), laser-assisted subepithelial keratomileusis (LASEK), and LASEK combined with corneal collagen cross-linking (LASEK-CXL) surgery for high-degree myopia. METHODS: Medical records of patients with spherical equivalent (SE) greater than -6.00 diopters (D) treated with SMILE, LASEK, and LASEK-CXL were reviewed. Uncorrected distance visual acuity (UCVA), SE, and corneal haze were followed up in the 3 groups for 6 months. RESULTS: The SMILE group included 69 eyes, the LASEK group included 61 eyes, and the LASEK-CXL group included 40 eyes. At 6 months postoperatively, there were no statistically significant differences in UCVA between the SMILE, LASEK, and LASEK-CXL groups (logMAR 0.00 ± 0.00, 0.01 ± 0.08, and 0.01 ± 0.08, respectively, P = 0.69). The averages of the absolute value of SE were 0.34 ± 0.25 D, 0.50 ± 0.36 D, and 0.42 ± 0.34 D in the SMILE, LASEK, and LASEK-CXL groups, respectively (P = 0.04). The percentages of the patients with a postoperative residual refractive error within ±0.50 D were 84% in the SMILE group, 65% in the LASEK group, and 76% in the LASEK-CXL group. The percentages of the patients with greater than 20/25 postoperative UCVA were 100%, 91%, and 95%, respectively. SMILE produced no postoperative corneal haze. However, 18% of patients treated with LASEK and 25% of those treated with LASEK-CXL had corneal haze at 6 months postoperatively. CONCLUSIONS: SMILE, LASEK, and LASEK-CXL surgery appear to be safe and effective for high-degree myopic correction. However, the SMILE group had no haze and fewer induction of some higher-order aberrations compared with the LASEK and LASEK-CXL groups.

Increased frequency of osteoporosis and BMD below the expected range for age among South Korean women with rheumatoid arthritis.

OBJECTIVE: To compare the frequency of osteoporosis and bone mineral density (BMD) below the expected range for age between female patients with rheumatoid arthritis (RA) and healthy subjects and to determine risk factors for bone loss in female patients with RA. METHOD: Two hundred and ninety-nine patients with RA and 246 age-matched healthy subjects were included in this study. BMD in the lumbar spine, femoral neck and total hip were measured with dual-energy X-ray absorptiometry. A T-score of -2.5 or lower in postmenopausal women was defined as osteoporosis, and a Z-score -2.0 or lower in females prior to menopause was defined as below the expected range for age. RESULT: The frequency of osteoporosis in the RA patients (22.1%) was significantly higher than in healthy subjects (11.4%) at either the spine or hip (P = 0.014). The occurrence of BMD below the expected range for age in RA patients (7.8%) was also significantly higher than in healthy subjects (1.0%, P = 0.015). In 299 female patients with RA, higher age, lower body mass index and postmenopausal status were significantly associated with the lumbar spine and hip BMD reduction. Of disease-related variables, glucocorticoid use was independently associated with reduction of hip BMD. CONCLUSION: The prevalence of osteoporosis in the RA patients was 1.9 times higher than in healthy subjects. Glucocorticoid use was a risk factor for generalized bone loss in female RA patients.