Background: Cytoplasmic polyadenylation element binding (CPEB) proteins are sequencespecific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study. Objective: This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing. Methods: CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively. Results: Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased. Conclusion CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.

Nontuberculous mycobacterial (NTM) pulmonary disease generally occurs in old people with underlying lung disease. However, unlike adults, NTM infections in children with normal immunity are rare, and they occasionally manifest as lymphadenitis. We herein present a rare case of NTM pulmonary disease in a girl who is the youngest patient reported in Korea. A 16-year-old female was brought to the hospital because of dyspnea on exertion, fever, and productive cough. The patient had bronchiectasis. She underwent Fontan operation for right isomerism, double outlet right ventricle, pulmonary stenosis, and had been taking prophylactic antibiotics for asplenia. NTM were found in the sputum and bronchoalveolar lavage fluid by acid fast bacillus (AFB) staining and culture, which were identified as Mycobacterium avium. The treatment started with azithromycin, ethambutol and rifampicin. After 6 months of treatment, respiratory symptoms improved and the sputum AFB culture became negative. She is currently on medication with above-mentioned drugs for 10 months without any adverse effects. This case suggests that NTM pulmonary disease should be suspected and properly treated especially in children and adolescents with underlying lung disease.

Objective: : The extensive vasa vasorum network functions as a conduit for the entry of inflammatory cells or factors that promote the progression of angiogenesis and plaque formation. Therefore, we investigated the correlation between the carotid vasa vasorum activities and carotid plaque vulnerability using indocyanine green video angiography (ICG-VA) during carotid endarterectomy (CEA). Methods: : Sixty-nine patients who underwent CEA were enrolled prospectively from September 2015 to December 2017. During CEA, a bolus of ICG was injected intravenously before and after resecting the atheroma. Additionally, we performed immunohistochemistry using CD68 (a surface marker of macrophages), CD117 (a surface marker of mast cells), and CD4 and CD8 (surface markers of T-cells) antibodies to analyze the resected plaque specimens. Results: : The density of active vasa vasorum was observed in all patients using ICG-VA. The vasa vasorum externa (VVE) and interna (VVI) were seen in 11 (16%) and 57 patients (82.6%), respectively. Macroscopically, the VVE-type patterns were strongly associated with preoperative angiographic instability (81.8%, p=0.005) and carotid plaque vulnerability (90.9%, p=0.017). In contrast, the VVI-type patterns were weakly associated with angiographic instability (31.6%) and plaque vulnerability (49.1%). CD68-stained macrophages and CD117-stained mast cells were observed more frequently in unstable plaques than in stable plaques (p<0.0001, p=0.002, respectively). Conclusion : The early appearance of VVE, along with the presence of many microvessel channels that provided nutrients to the developing and expanding atheroma during ICG-VA, was strongly associated with unstable carotid plaques. The degree of infiltration of macrophages and mast cells is possibly related to the formation of unstable plaques.

PURPOSE: We compared the outcomes of laser iridotomy and primary phacoemulsification when treating acute angle-closure glaucoma. METHODS: This study was conducted with 61 patients diagnosed with acute angle closure glaucoma from January, 2005 to January, 2015. The patients received either laser iridotomy or primary phacoemulsification. The age and gender of each patient, differences of intraocular pressure (IOP) before and after treatment, visual acuity, need for IOP lowering agents and complications were analyzed retrospectively at 1-day, 1-month, 6-month and 12-month after the treatment. Patients who received laser iridotomy with phacoemulsification or trabeculectomy were excluded from this study. Additionally, we included only cases in which treatments were given within 3 days after the onset of symptom. RESULTS: Among the 61 patients, 45 patients received laser iridotomy and 16 patients received primary phacoemulsification. One day after the treatment the laser iridotomy group showed better outcome in their visual acuity (log MAR 0.62 +/- 0.51; p = 0.048). At 6-month postoperatively, the primary phacoemulsification group showed better visual acuity (log MAR 0.07 +/- 0.15; p = 0.013). However, at 12-month postoperatively, the visual acuities were not significantly different between the 2 groups. Regarding IOP, at postoperative 1-month, the group of primary phacoemulsification shows significantly lower IOP (9.5 +/- 1.3 mm Hg), compared with the group of laser iridotomy. A significant difference was observed in the number of IOP lowering agents that patients at 12 month after the treatment. There were no severe complications in either group. CONCLUSIONS: Following the initial treatment of acute angle-closure glaucoma, the primary phacoemulsification showed no significant differences in postoperative visual acuity, IOP and complications compared to the outcomes of laser iridotomy. Additionally, the need for IOP lowering agents was less in the primary phacoemulsification groups at 1 year after the operation.
Glaucoma, Angle-Closure* ; Humans ; Intraocular Pressure ; Phacoemulsification* ; Retrospective Studies ; Trabeculectomy ; Visual Acuity

PURPOSE: Our previous study demonstrated the hypoglycemic effects of mulberry (Morus alba L.) leaf and the underlying mechanisms. Here we explored the potency of mulberry twigs (TW) and root barks (RB) in postprandial hypoglycemic effects in vitro and in vivo. METHODS: The major components of TW and RB were determined by high performance liquid chromatography (HPLC). Alpha-glucosidase inhibition and glucose/fructose uptake inhibition in Caco-2 cells were determined for TW, RB, and their major components, followed by an oral sugar tolerance test (OSTT) in streptozotocin-induced diabetic rats. Male Wistar rats were fed a high-fat diet for 2 weeks and then a single dose of streptozotocin (35 mg/kg B.W) was administered by intraperitoneal injection. Rats with fasting blood glucose levels above 126 mg/dL were randomly divided into 5 groups (n = 8/group) for the following treatments by gavage for 4 weeks: vehicle (normal control and diabetic control), 200 mg/kg B.W of TW or RB or 100 mg/kg B.W of oxyresveratrol (OXY). RESULTS: OXY and mulberroside A were identified as the major components of TW and OXY, mongolicin, and kuwanon H for RB. A significant inhibitory activity on alpha-glucosidase was found for TW, RB, and OXY (p = 0.0099). There was a dose-dependent inhibition of TW and RB on the intestinal sugar uptakes in Caco-2 cells, showing a greater impact on fructose compared to glucose. The OSTT showed that TW and RB significantly delayed time to maximal concentration (p = 0.0088) and decreased maximal concentration (p = 0.0043) compared to the control group. CONCLUSION: These results suggest that TW and RB may have a postprandial hypoglycemic effect, particularly in the case of high fructose or sucrose intake. OXY was suggested as a contributor to the hypoglycemic effect of TW and RB. Further studies are needed for the systemic effect of TW and RB in circulation.
alpha-Glucosidases ; Animals ; Blood Glucose ; Caco-2 Cells ; Chromatography, Liquid ; Diet, High-Fat ; Fasting ; Fructose ; Glucose ; Humans ; Hypoglycemic Agents* ; Injections, Intraperitoneal ; Male ; Morus* ; Rats ; Rats, Wistar ; Streptozocin ; Sucrose

PURPOSE: This study evaluated the predictive performance of a combination of self-report questionnaires, salivary hemoglobin levels, and age as a non-invasive screening method for periodontitis. METHODS: The periodontitis status of 202 adults was examined using salivary hemoglobin levels, responses to 10 questions on a self-report questionnaire, and the Community Periodontal Index (CPI). The ability of those two variables and the combination thereof with age to predict the presence of CPI scores of 3-4 and 4 was assessed using logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: CPI scores of 3-4 and 4 were present among 79.7% and 46.5% of the sample, respectively. The area under the ROC curves (AUROCs) of salivary hemoglobin levels for predicting prevalence of CPI scores of 3-4 and 4 were 0.63 and 0.67, respectively (with sensitivity values of 71% and 60% and specificity values of 56% and 72%, respectively). Two distinct sets of five questions were associated with CPI scores of 3-4 and 4, with AUROCs of 0.73 and 0.71, sensitivity values of 76% and 66%, and specificity values of 63% and 69%. The combined model incorporating both variables and age showed the best predictive performance, with AUROCs of 0.78 and 0.76, sensitivity values of 71% and 65%, and specificity values of 68% and 77% for CPI scores of 3-4 and 4, respectively. CONCLUSIONS: The combination of salivary hemoglobin levels and self-report questionnaires was shown to be a valuable screening method for detecting periodontitis.
Adult ; Humans ; Logistic Models ; Mass Screening* ; Periodontal Diseases ; Periodontal Index ; Periodontitis* ; Prevalence ; ROC Curve ; Saliva ; Self Report ; Sensitivity and Specificity

There have been a small number of cases of scrub typhus-associated hemophagocytic syndrome (HPS), most of which were treated successfully using adequate antibiotics. Here, we report a case of Epstein-Barr virus (EBV)-associated HPS after scrub typhus infection that was not improved using antirickettsial treatment. A 73-year-old male who had been diagnosed with scrub typhus according to an eschar and a positive serology was transferred to our institution because of a persistent fever despite 7-day doxycycline therapy. Physical and laboratory data showed hepatosplenomegaly, bicytopenia, hyperferritinemia, and hypofibrinogenemia. A bone marrow examination (BM) revealed hypercellular marrow with hemophagocytosis and histiocyte infiltration. EBV was detected in BM aspirates using polymerase chain reaction. After a diagnosis of HPS was made, the patient was treated successfully using high-dose steroids.
Aged ; Anti-Bacterial Agents ; Bone Marrow ; Bone Marrow Examination ; Diagnosis ; Doxycycline ; Epstein-Barr Virus Infections ; Fever ; Herpesvirus 4, Human* ; Histiocytes ; Humans ; Lymphohistiocytosis, Hemophagocytic* ; Male ; Polymerase Chain Reaction ; Scrub Typhus* ; Steroids

Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing K⁺ channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward K⁺ current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing K⁺ channels (TASK-2). NIOK in the presence of K⁺ channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.
Acidosis ; Animals ; Blotting, Western ; Bupivacaine ; Estrogens ; Female ; Isometric Contraction ; Lidocaine ; Methionine ; Mice* ; Microscopy, Confocal ; Muscle, Smooth ; Myometrium ; Oxytocin ; Pregnancy ; Quinidine ; Relaxation* ; Tea ; Uterine Contraction ; Uterus

PURPOSE: Non-intraocular pressure (IOP) factors such as vascular factors have been identified as contributing to normal tension glaucoma. However, there is not an established range of haemorheological factors considered normal, nor are there standardized tests. In this study, we investigated differences in blood viscosity and haemorheological parameters between patients with normal tension glaucoma (NTG) and normal controls using a new instrument called the BVD-RO1 (BIO-VISCO. Inc., Jeonju, Korea). METHODS: Twenty patients with NTG and 20 age-matched normal controls were included in the study. Haemorheological parameters of the venous blood samples, including blood viscosity at the shear rates of 300 (high shear rate) and 1 (low shear rate) s-1 were measured using an automated scanning capillary tube viscometer. RESULTS: More hematocrit concentration was detected in the NTG group than in the control group (p < 0.05). Furthermore, higher blood viscosities at the high (p < 0.01) and low (p < 0.01) shear rates were found in the NTG group. CONCLUSIONS: The NTG patients differed in blood viscosity with the control group. This may signify the importance of hemodynamic factors in the pathogenesis of NTG.
Blood Viscosity* ; Capillaries ; Hematocrit ; Hemodynamics ; Humans ; Jeollabuk-do ; Low Tension Glaucoma*