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.

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

The typical presentation of intussusception includes intermittent severe abdominal pain, vomiting, rectal bleeding, and the presence of an abdominal mass. We present a case of intussusception after abdominal blunt trauma along with a literature review. A 4-year-old girl was admitted to the emergency department after a bicycle accident. She complained of progressively worsening abdominal pain, but there was no vomiting, fever, bloody stool, or abdominal mass. She was finally diagnosed with traumatic intussusception by ultrasonography and treated with air reduction. Because the typical symptoms are unusual in traumatic intussusception, close attention must be paid to avoid a delayed diagnosis.
Abdominal Pain ; Child, Preschool ; Delayed Diagnosis ; Emergency Service, Hospital ; Female ; Fever ; Hemorrhage ; Humans ; Intussusception* ; Pediatrics ; Ultrasonography ; Vomiting ; Wounds and Injuries

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

OBJECTIVES: This clinical study aimed to investigate if dentifrices containing policresulen would help to control dental plaque and gingivitis. METHODS: Seventy-eight eligible adults participated in this double-blind and randomized clinical study after an initial oral examination, calculus removal, and tooth prophylaxis. Two weeks after the procedure, the participants were assigned to three groups using the following dentifrices: (1) a dentifrice containing 0.22% NaF (control group); (2) a dentifrice containing 0.22% NaF and 100 ppm policresulen (policresulen group); and (3) a dentifrice containing 0.22% NaF, 100 ppm policresulen, and 1.00% bamboo salt (policresulen/bamboo group). The participants used only the provided dentifrice (for 1 min, twice a day, over 8 weeks) when brushing their teeth and followed their normal brushing habits. Dental plaque accumulation and gingivitis measurements were conducted using the Turesky modification of the Quigley-Hein plaque index (PI), the Loe and Silness gingival index (GI), and the percent bleeding on probing (%BOP) to obtain baseline data and 4- and 8-week data after grouping. RESULTS: A total of 73 participants aged 35.92+/-11.46 years (mean+/-SD) completed the study. The results after 8 weeks demonstrated statistically significant group-by-time interactions for PI, GI, and %BOP (P<0.001). The PI observed in the control groups increased over time up to 6%, while that observed in the dentifrice groups containing policresulen decreased by 5% (P<0.001). For GI and %BOP, the control group exhibited significantly higher values after 8 weeks, while the policresulen and the policresulen/bamboo groups revealed similar index values as the baseline after 4 and 8 weeks. The changes in all indices were significantly different between the control and the two experimental groups. There were no significant differences in the results obtained from the policresulen/bamboo group and the results obtained from the policresulen group. CONCLUSIONS: Use of dentifrices containing policresulen over 8 weeks demonstrated anti-plaque and anti-gingivitis efficacy compared to a control dentifrice.
Adult ; Calculi ; Dental Plaque Index ; Dental Plaque* ; Dentifrices* ; Diagnosis, Oral ; Gingival Hemorrhage ; Gingivitis* ; Hemorrhage ; Humans ; Periodontal Index ; Tooth

BACKGROUND/AIMS: Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. METHODS: Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. RESULTS: Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. CONCLUSIONS: Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.
Antineoplastic Agents/*pharmacology ; Carcinoma, Hepatocellular/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cell Survival/drug effects ; Down-Regulation/drug effects ; Drug Screening Assays, Antitumor ; Drug Synergism ; Humans ; Liver Neoplasms/metabolism/pathology ; Niacinamide/*analogs & derivatives/pharmacology ; Phenylurea Compounds/*pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Quinazolines/*pharmacology ; Receptor, Epidermal Growth Factor/metabolism ; Signal Transduction/drug effects ; Silymarin/*pharmacology

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*

BACKGROUND/AIMS: Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. METHODS: Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. RESULTS: Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT] > 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). CONCLUSIONS: Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.
4-Hydroxycoumarins/*poisoning ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alcohol Drinking/adverse effects/blood ; Anticoagulants/*poisoning ; Blood Coagulation/*drug effects ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Partial Thromboplastin Time ; Prothrombin Time ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Rodenticides/*poisoning ; Serum Albumin/metabolism ; Vitamin K/*blood ; Vitamin K Deficiency Bleeding/blood/*chemically induced/diagnosis/therapy ; Young Adult

BACKGROUND/AIMS: For many years, conventional treatment for multiple myeloma (MM) not ineligible for high-dose therapy has been the combination of oral melphalan and prednisone (MP). However, melphalan-based regimens are associated with numerous complications. Another alkylating agent, cyclophosphamide, has similar effects on MM and is associated with fewer reports of complications. Therefore, cyclophosphamide-based regimens have usually been used as salvage therapy in patients with refractory or relapsed MM, despite the development of newer drugs. The purpose of this report was to evaluate the efficacy and tolerability of cyclophosphamide and prednisone as a first-line therapy for MM. METHODS: For the period January 2002 to June 2012, we retrospectively analyzed 29 patients newly diagnosed with MM who underwent a treatment regimen consisting of intravenous cyclophosphamide (1,000 mg/kg) for 1 day and prednisone (100 mg) for 4 days. RESULTS: The rate of response to this regimen was 31.1 percent. The median progression-free survival (PFS) was 5.5 months and the median overall survival (OS) was 47.3 months. The regimen was well tolerated. Adverse effects of grades above III were as follows: anemia in seven patients (24.1%), neutropenia in five patients (17.2%), and thrombocytopenia in two patients (6.8%). These adverse effects were easily adjusted. No one developed a secondary malignancy or hemorrhagic cystitis. CONCLUSIONS: Although PFS was less than for the MP regimen, median OS was better than for the MP regimen. Furthermore, the cyclophosphamide-prednisone regimen was well tolerated, and the adverse effects that did occur were easily adjusted. The cyclophosphamide-prednisone combination regimen may represent an effective and well tolerated first-line therapy for non-transplant candidates with MM.
Anemia ; Antineoplastic Combined Chemotherapy Protocols ; Cisplatin ; Cyclophosphamide ; Disease-Free Survival ; Humans ; Melphalan ; Methotrexate ; Multiple Myeloma ; Neutropenia ; Prednisone ; Retrospective Studies ; Salvage Therapy ; Thrombocytopenia