BACKGROUND: Staphylococcal scalded skin syndrome (SSSS) is a blistering disease of superficial skin mediated by Staphylococcus aureus (S. aureus) exfoliative toxin. Generally, SSSS affects mainly infants and children younger than 5 years and has a good prognosis. However, an increasing number of cases of methicillin-resistant S. aureus (MRSA) have been reported recently. OBJECTIVE: The purposes of this study were to evaluate the clinical features and course, to investigate the microbiological manifestations, and to perform antimicrobial susceptibility testing of SSSS among Korean children. METHODS: From March 2003 to July 2016, a total of 141 children were included in this study. The patients were divided into two different groups according to time of onset of their disease: before or after September 2011. We retrospectively reviewed medical records, microbiological results, bacterial detection sites, and antimicrobial susceptibility tests of all participating children. The results of comparison between the two groups were evaluated using the chi-square test. RESULTS: S. aureus infections were identified in all patients. Among all cultured S. aureus specimens, 63.1% (89/141) showed methicillin resistance. Beginning in September 2011, MRSA infection showed a significantly higher prevalence than that previously demonstrated (71.7% vs. 38.8%; p=0.0010). Moreover, MRSA infections were detected on the skin and neck and in the nose (each detected on 61, 41, and 18 occasions, respectively) with overlap observed in many cases. CONCLUSION: In conclusion, since the prevalence of MRSA infection has been gradually increasing in recent years, careful consideration is needed in the selection of antibiotics covering MRSA.
Anti-Bacterial Agents ; Blister ; Child ; Humans ; Infant ; Medical Records ; Methicillin Resistance* ; Methicillin-Resistant Staphylococcus aureus* ; Neck ; Nose ; Prevalence ; Prognosis ; Retrospective Studies ; Skin ; Staphylococcal Scalded Skin Syndrome* ; Staphylococcus aureus

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor of many solid tumors, promoting vascularization and formation of metastases. In an attempt to generate effective VEGF inhibitors, the authors constructed the VEGF receptor mutants, expressed in E. coli and Sf9 insect cells, and examined their binding to VEGF. MATERIALS AND METHODS: The cDNA fragment encoding FLT-1 extracellular domain was cloned from human umbilical vein endothelial (HUVE) cell total RNA using RT-PCR. PCR- subcloning was performed using this template, in order to generate the deletion mutants by introducing FLT-1 partial sequences into E.coli expression vector pET-21d and baculovirus transfer vactors, pBAC-1 and pBAC-3. Two mutant proteins from baculovirus-infected insect cells were purified by heparin sepharose chromatography and immobilized into nitrdegrees Cellulose membrane followed by 125I-VEGF binding assay. RESULTS: Two mutant receptors, sFLT (1~7) and sFLT (2~4) expressed in E.coli appeared in inclusion body as insoluble proteins. The soluble mutant receptors were produced in low yield by baculovirus/insect cell expression system. Both immobilized mutant receptors, sFLT (1~7) and sFLT (2~4) were able to bind VEGF. CONCLUSION: These results suggest that a small soluble mutant receptor, sFLT (2~4), as well as sFLT (1~7) may be used effectively for bldegrees Cking angiogenic function of VEGF.
Angiogenesis Inducing Agents ; Baculoviridae ; Cellulose ; Chromatography, Agarose ; Clone Cells ; DNA, Complementary ; Heparin ; Humans ; Inclusion Bodies ; Insects ; Membranes ; Mutant Proteins ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; Receptors, Vascular Endothelial Growth Factor* ; RNA ; Umbilical Veins ; Vascular Endothelial Growth Factor A*

Chondroitin sulfate proteoglycan (CSPG) inhibits neurite outgrowth of various neuronal cell types, and CSPG-associated inhibition of neurite outgrowth is mediated by the Rho/ROCK pathway. Mesenchymal stromal/stem cells (MSCs) have the potential to differentiate into neuron-like cells under specific conditions and have been shown to differentiate into neuron-like cells by co-treatment with the ROCK inhibitor Y27632 and the hypoxia condition mimicking agent CoCl2. In this study, we addressed the hypothesis that a ROCK inhibitor might be beneficial to regenerate neurons during stem cell therapy by preventing transplanted MSCs from inhibition by CSPG in damaged tissues. Indeed, dose-dependent inhibition by CSPG pretreatment was observed during morphological changes of Wharton's jelly-derived MSCs (WJ-MSCs) induced by Y27632 alone. The formation of neurite-like structures was significantly inhibited when WJ-MSCs were pre-treated with CSPG before induction under Y27632 plus CoCl2 conditions, and pretreatment with a protein kinase C inhibitor reversed such inhibition. However, CSPG treatment resulted in no significant inhibition of the WJ-MSC morphological changes into neuron-like cells after initiating induction by Y27632 plus CoCl2. No marked changes were detected in expression levels of neuronal markers induced by Y27632 plus CoCl2 upon CSPG treatment. CSPG also blocked the morphological changes of human bone marrow-derived MSCs into neuron-like cells under other neuronal induction condition without the ROCK inhibitor, and Y27632 pre-treatment blocked the inhibitory effect of CSPG. These results suggest that a ROCK inhibitor can be efficiently used in stem cell therapy for neuronal induction by avoiding hindrance from CSPG.
Anoxia ; Chondroitin Sulfate Proteoglycans* ; Chondroitin Sulfates* ; Chondroitin* ; Humans ; Neurites ; Neurons ; Protein Kinase C ; Stem Cells

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.
Apoptosis ; Autophagy* ; Caspase 3 ; Chloroquine ; Endothelial Cells* ; Fibroblast Growth Factor 2 ; Helminths ; Intercellular Signaling Peptides and Proteins ; Mebendazole* ; Microtubules ; Phosphorylation ; Phosphotransferases ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A

Background: Acanthosis nigricans is characterized by a velvety thickening of the epidermis accompanied by different degrees of hyperpigmentation, and known to be linked to obesity and insulin resistance. Objective: We aimed to analyze obesity-related factors in acanthosis nigricans patients and to evaluate the correlations between acanthosis nigricans and various factors. Methods: From January 2004 to February 2015, 27 acanthosis nigricans patients participated in this study. Blood samples were collected from a control group of seven overweight people and from the seven acanthosis nigricans patients, and they were analyzed for different obesity-related factors. Skin samples were collected from the 23 acanthosis nigricans patients and from 11 patients with epidermal nevi, and immunohistochemistry was performed to detect the presence of adiponectin receptor 1, adiponectin receptor 2, and the leptin receptor. Results: The median serum leptin level in the acanthosis nigricans patients (13 ng/mL) was significantly higher than that in the overweight control individuals (8.9 ng/mL) (p=0.021). The acanthosis nigricans patients had significantly higher levels of insulin-like growth factor-1 in their serum samples (p=0.017). The immunohistochemical analysis determined that the skin from the acanthosis nigricans patients stained significantly more intensely for the leptin receptor compared with that seen in the skin from the patients with epidermal nevi (p=0.002). Conclusion In conclusion, this study’s findings suggest that the levels of leptin and insulin-like growth factor-1 in the serum, and the expression of the leptin receptor in the skin are elevated with acanthosis nigricans.

Azathioprine is an immunosuppressive drug that has been widely used in dermatology for the treatment of immunobullous diseases. Myelosuppression is the most important side effect and requires close observation of the complete blood cell count. The clinical findings of myelosuppression include general weakness, poor oral intake, nausea, dyspnea, and pallor. It can occur within several weeks to years after initial azathioprine treatment; thus, a weekly full blood count for the first 4 weeks, followed by reduced frequency of monitoring to a minimum of once every 3 months is recommended. If the myelosuppression is not treated properly, it can lead to fever, secondary infection, sepsis, and even death. Herein, we present three educational cases for dermatologists to order to underline the risk of myelosuppression during azathioprine treatment.
Azathioprine* ; Blood Cell Count ; Coinfection ; Dermatology ; Dyspnea ; Fever ; Nausea ; Pallor ; Sepsis

Autophagy is a process of eliminating damaged or unnecessary proteins and organelles, thereby maintaining intracellular homeostasis. Deregulation of autophagy is associated with several diseases including cancer. Contradictory dual roles of autophagy have been well established in cancer. Cytoprotective mechanism of autophagy has been extensively investigated for overcoming resistance to cancer therapies including radiotherapy, targeted therapy, immunotherapy, and chemotherapy. Selective autophagy inhibitors that directly target autophagic process have been developed for cancer treatment. Efficacies of autophagy inhibitors have been tested in various pre-clinical cancer animal models. Combination therapies of autophagy inhibitors with chemotherapeutics are being evaluated in clinal trials. In this review, we will focus on genetical and pharmacological perturbations of autophagy-related proteins in different steps of autophagic process and their therapeutic benefits. We will also summarize combination therapies of autophagy inhibitors with chemotherapies and their outcomes in pre-clinical and clinical studies. Understanding of current knowledge of development, progress, and application of cytoprotective autophagy inhibitors in combination therapies will open new possibilities for overcoming drug resistance and improving clinical outcomes.

Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality throughout the world, is a highly complicated disease that includes chronic airway inflammation, airway remodeling, emphysema, and mucus hypersecretion.For respiratory function, an intact lung structure is required for efficient air flow through conducting airways and gas exchange in alveoli. Structural changes in small airways and inflammation are major features of COPD. At present, mechanisms involved in the genesis and development of COPD are poorly understood. Currently, there are no effective treatments for COPD. To develop better treatment strategies, it is necessary to study mechanisms of COPD using proper experimental models that can recapitulate distinctive features of human COPD. Therefore, this review will discuss representative established mouse models to investigate inflammatory processes and basic mechanisms of COPD. In addition, human COPD-mimicking human lung organoid models are introduced to help researchers overcome limits of mouse COPD models.

Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality throughout the world, is a highly complicated disease that includes chronic airway inflammation, airway remodeling, emphysema, and mucus hypersecretion.For respiratory function, an intact lung structure is required for efficient air flow through conducting airways and gas exchange in alveoli. Structural changes in small airways and inflammation are major features of COPD. At present, mechanisms involved in the genesis and development of COPD are poorly understood. Currently, there are no effective treatments for COPD. To develop better treatment strategies, it is necessary to study mechanisms of COPD using proper experimental models that can recapitulate distinctive features of human COPD. Therefore, this review will discuss representative established mouse models to investigate inflammatory processes and basic mechanisms of COPD. In addition, human COPD-mimicking human lung organoid models are introduced to help researchers overcome limits of mouse COPD models.

Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality throughout the world, is a highly complicated disease that includes chronic airway inflammation, airway remodeling, emphysema, and mucus hypersecretion.For respiratory function, an intact lung structure is required for efficient air flow through conducting airways and gas exchange in alveoli. Structural changes in small airways and inflammation are major features of COPD. At present, mechanisms involved in the genesis and development of COPD are poorly understood. Currently, there are no effective treatments for COPD. To develop better treatment strategies, it is necessary to study mechanisms of COPD using proper experimental models that can recapitulate distinctive features of human COPD. Therefore, this review will discuss representative established mouse models to investigate inflammatory processes and basic mechanisms of COPD. In addition, human COPD-mimicking human lung organoid models are introduced to help researchers overcome limits of mouse COPD models.