Effects of Y-27632, a Rho-associated Kinase Inhibitor, on Human Corneal Endothelial Cells Cultured by Isolating Human Corneal Endothelial Progenitor Cells.

CONCLUSIONS: Y-27632 enabled the isolation and expansion of HCEPs. It also enhanced the proliferation, viability, and migration of differentiated HCEPs. METHODS: HCEPs were isolated and expanded in a medium with and without 10µM Y-27632, and then differentiated into HCECs in a medium with fetal bovine serum. The characteristics of HCEPs and differentiated HCEPs were confirmed by immunofluorescence staining. The proliferation, viability, morphology, and wound-healing ability of differentiated HCEPs were assessed in the presence of different concentrations of Y-27632. PURPOSE: Human corneal endothelial progenitor cells (HCEPs), which has been selectively isolated and differentiated into human corneal endothelial cells (HCECs), are crucial for repairing corneal endothelial damage. In this study, we evaluated the roles of a Rho-assisted kinase (ROCK) inhibitor, Y-27632, on the isolation and expansion of HCEPs, and assessed the in vitro effects of different concentrations of Y-27632 on the differentiated HCEPs. RESULTS: Y-27632 enabled the isolation and expansion of HCEPs from the corneal endothelium. The differentiated HCEPs showed an optimal increase in proliferation and survival in the presence of 10µM Y-27632. As the concentration of Y-27632 increased, differentiated HCEPs became elongated, and actin filaments were redistributed to the periphery of cells. Y-27632 also caused a concentration-dependent enhancement in the wound-healing ability of differentiated HCEPs.

Clinical Characteristics of Lamellar Macular Hole Subtypes: Degenerative and Tractional.

PURPOSE: To analyze clinical parameters of two subtypes of lamellar macular hole (LMH): degenerative and tractional. METHODS: This retrospective chart review study included patients monitored for more than 6 months after the initial diagnosis of LMH from January 2011 to January 2018. LMH was classified in two subtypes: degenerative and tractional. The following parameters between both subtypes were assessed: central subfield thickness (CST), maximum inner diameter (MID), maximum outer diameter (MOD), MID/MOD ratio, inner and outer segment (IS/OS) junction disruption, residual retinal thickness (RRT), subfoveal choroidal thickness (SFCT), best-corrected visual acuity (BCVA), anatomical progression rate, and percentage of patients undergoing surgery. RESULTS: This study included 51 eyes with a mean follow-up period of 18.94 months: 33 eyes with tractional LMH and 18 eyes with degenerative LMH. MID was not significantly different between both subtypes but MOD was significantly greater in tractional LMH than degenerative types (tractional, 1131.6 µm; degenerative, 708.9 µm; p < 0.001). The MID were significantly increased in degenerative eyes, while the tractional eyes featured a significant increase in MOD. BCVA was not significantly different between both subtypes at baseline and the last follow-up. Epiretinal membrane presence was significantly different between the two subtypes (tractional, 96.9%; degenerative, 22.2%; p < 0.001). Ellipsoid defect and rate of receiving surgery were not significantly different between both subtypes. The anatomical progression rate in tractional eyes (81.8%) was significantly higher than that of degenerative LMH (27.7%) (p = 0.010). The SFCT was correlated to anatomical progression in the tractional LMH (correlation coefficient = 0.351, p = 0.049) but not in the degenerative LMH. During the follow-up period, 4 eyes (22.2%) of the degenerative LMH and 11 eyes (33.3%) of the tractional LMH underwent surgery. CONCLUSIONS: We found that greater SFCT at baseline was correlated to anatomical progression of tractional LMH. Therefore, it is expected that SFCT could be used as a biomarker to predict anatomical progression in tractional LMH.

Amelioration of trinitrobenzene sulfonic acid-induced colitis in mice by liquiritigenin.

BACKGROUND AND AIM: The anti-inflammatory effects of liquiritigenin, a major flavonoid isolated from Glycyrrhizae uralensis, have been reported in many inflammation models. However, its protective effects have not been reported in a colitis model. This study investigated the anti-inflammatory effect and mechanism of liquiritigenin for trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. METHODS: Male mice imprinting control regions (ICR) were randomly divided into five groups: normal, TNBS-induced colitis, colitis treated with liquiritigenin at low dose (10 mg/kg) and high dose (20 mg/kg), or mesalazine (10 mg/kg). TNBS colitis induction was performed except for in the normal group, and they were treated with liquiritigenin or mesalazine except control group. The treatment effect was measured after three days treatment, by body weight, colon length, macroscopic score, histological score, levels of cytokines (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, and IL-10) in colon tissue as well as the nuclear factor kappa-light-chain-enhancer pathway of activated B cells (NF-κB) activation. RESULTS: Mice treated with high-dose liquiritigenin showed significant body weight gain, inhibition of colon shortening, protective effect on histological damages, and myeloperoxidase activity of colon tissue compared with the control group. Furthermore, mice treated with high-dose liquiritigenin experienced significantly suppressed tumor necrosis factor-α, IL-1ß, and IL-6 as well as enhanced IL-10 expression (all P < 0.05). High-dose liquiritigenin treatment group showed significant decreases in TNBS-induced phosphorylation of IKKß, p65, and IκB-α. CONCLUSION: Liquiritigenin may ameliorate TNBS-induced colitis in mice by suppressing expression of pro-inflammatory cytokines through NF-κB pathway.

The effects of the standardized herbal formula PM014 on pulmonary inflammation and airway responsiveness in a murine model of cockroach allergen-induced asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: PM014 is a modified form of the Chung-Sang-Bo-Ha-Tang (CSBHT) herbal formula that has been used to treat chronic pulmonary diseases in Korea for centuries. Previously, we developed a formulation of PM014 based on a series of in vitro and in vivo screening efforts that comprises seven herbal extracts. The PM014 formula includes the root of Rehmannia glutinosa, the cortex of Paeonia suffruticosa, the fruit of Schizandra chinensis, the root of Asparagus cochinchinensis, seeds of Prunus armeniaca, the root of Scutellaria baicalensis and the root of Stemona sessilifolia. Asthma is a chronic inflammatory disease of the lungs that is characterized by wheezing, bronchial contraction, and chest tightness. In addition, the airway becomes hypersensitive and narrows through an inflammatory reaction mediated by Th2 cells. The present study was conducted to evaluate the ability of PM014 to prevent allergic airway inflammation and to attenuate airway responses in a cockroach allergen-induced mouse model. MATERIALS AND METHODS: Mice sensitized to and challenged with cockroach allergen were treated with oral administration of PM014. Airway resistance was determined by whole body plethysmography. In addition, Th2 cytokines and immune cell profiles of bronchoalveolar lavage (BAL) fluid and inflammatory mediators in serum were analyzed by ELISA. A series of histological examinations were also conducted to demonstrate the effects of PM014 on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. RESULTS: PM014 significantly inhibited the number of total cells, eosinophils, neutrophils, macrophages and lymphocytes in the BAL fluid of mice that were challenged with cockroach allergen. In addition, PM014 reduced the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in the BAL fluid and inflammatory mediators such as IgE in the serum, as measured by enzyme-linked immunosorbent assay (ELISA). Histopathological analysis also showed that PM014 substantially inhibited eosinophil infiltration into the airway, goblet cell hyperplasia and smooth muscle hypertrophy. CONCLUSIONS: In this study, our results indicate that PM014 has significant effects on allergic airway inflammation upon exposure to cockroach allergen in a mouse model. According to these outcomes, PM014 may have therapeutic potential as a treatment for allergic asthma.

Effect of bee venom acupuncture on oxaliplatin-induced cold allodynia in rats.

Oxaliplatin, a chemotherapy drug, often leads to neuropathic cold allodynia after a single administration. Bee venom acupuncture (BVA) has been used in Korea to relieve various pain symptoms and is shown to have a potent antiallodynic effect in nerve-injured rats. We examined whether BVA relieves oxaliplatin-induced cold allodynia and which endogenous analgesic system is implicated. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water (4°C) and measuring the withdrawal latency. BVA (1.0 mg/kg, s.c.) at Yaoyangguan (GV3), Quchi (LI11), or Zusanli (ST36) acupoints significantly reduced cold allodynia with the longest effect being shown in the GV3 group. Conversely, a high dose of BVA (2.5 mg/kg) at GV3 did not show a significant antiallodynic effect. Phentolamine ( α -adrenergic antagonist, 2 mg/kg, i.p.) partially blocked the relieving effect of BVA on allodynia, whereas naloxone (opioid antagonist, 2 mg/kg, i.p.) did not. We further confirmed that an intrathecal administration of idazoxan ( α 2-adrenergic antagonist, 50 µ g) blocked the BVA-induced anti-allodynic effect. These results indicate that BVA alleviates oxaliplatin-induced cold allodynia in rats, at least partly, through activation of the noradrenergic system. Thus, BVA might be a potential therapeutic option in oxaliplatin-induced neuropathy.

Predicting factors of present hepatitis C virus infection among patients positive for the hepatitis C virus antibody.

BACKGROUND/AIMS: To identify the predicting factors of present hepatitis C virus (HCV) infection among patients with positivity for antibodies to HCV (anti-HCV). METHODS: We analyzed patients who showed positive enzyme immunoassay (EIA) results and performed an HCV RNA test as a confirmatory test at Kyung Hee University Hospital at Gangdong from June 2006 to July 2012. The features distinguishing the groups with positive and negative HCV RNA results were reviewed. RESULTS: In total, 490 patients were included. The results of the HCV RNA test were positive and negative in 228 and 262 patients, respectively. The index value of anti-HCV, mean age, platelet counts, total bilirubin, prothrombin time international normalized ratio, albumin and alanine transaminase (ALT) levels differed significantly between the two groups. On multivariable analysis, an index value of anti-HCV >10 [odds ratio (OR)=397.27, P<0.001), ALT >40 IU/L (OR=3.64, P=0.001), and albumin <3.8 g/dL (OR=2.66, P=0.014) were related to present HCV infection. CONCLUSIONS: Although EIA is not a quantitative test, considering the anti-HCV titer with ALT and albumin levels may be helpful in predicting present of HCV infection.