Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/ NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.

Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.

Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.

14-3-3γ plays diverse roles in different aspects of cellular processes. Especially in the brain where 14-3-3γ is enriched, it has been reported to be involved in neurological and psychiatric diseases (e.g. Williams-Beuren syndrome and Creutzfeldt-Jakob disease). However, behavioral abnormalities related to 14-3-3γ deficiency are largely unknown. Here, by using 14-3-3γ deficient mice, we found that homozygous knockout mice were prenatally lethal, and heterozygous mice showed developmental delay relative to wild-type littermate mice. In addition, in behavioral analyses, we found that 14-3-3γ heterozygote mice display hyperactive and depressive-like behavior along with more sensitive responses to acute stress than littermate control mice. These results suggest that 14-3-3γ levels may be involved in the developmental manifestation of related neuropsychiatric diseases. In addition, 14-3-3γ heterozygote mice may be a potential model to study the molecular pathophysiology of neuropsychiatric symptoms.
Animals ; Anxiety ; Brain ; Heterozygote ; Mice ; Mice, Knockout ; Williams Syndrome

Percutaneous trans-catheter aortic valve implantation (TAVI) is recommended for inoperable patients with severe aortic stenosis at high risk for conventional aortic valve replacement. Originally, TAVI was mostly performed under general anesthesia. Here we describe two cases of transfemoral TAVI performed under monitored anesthesia care (MAC) with dexmedetomidine. Dexmedetomidine provides sedation, analgesia with minimal respiratory depression. Although MAC during transfemoral TAVI has limitations, such as unexpected patient movement and difficulty in intra-procedural use of transesophageal echocardiography, MAC with dexmedetomidine is feasible with close monitoring, fluoroscopic guidance and the participation of experienced anesthesiologists.
Analgesia ; Anesthesia* ; Anesthesia, General ; Aortic Valve Stenosis ; Aortic Valve* ; Dexmedetomidine* ; Echocardiography, Transesophageal ; Heart Valve Prosthesis Implantation ; Humans ; Hypnotics and Sedatives ; Respiratory Insufficiency

PURPOSE: We investigated the causes, clinical features, and risk factors of bee venom anaphylaxis in Korea. METHODS: The medical records of the diagnosis of anaphylaxis during a 5-year period from the 14 hospitals in Korea have been retrospectively reviewed. Cases of bee venom anaphylaxis were identified among anaphylaxis patients, and subgroup analyses were done. RESULTS: A total of 291 patients were included. The common cause of bee species was vespid (24.6%) in bee venom anaphylaxis, followed by honeybee and vespid (8.8%), apitherapy (7.7%), and honeybee (2.0%), although the causative bee species were commonly unknown (56.9%). The severity of anaphylaxis was mostly mild-moderate (72.9%), and common clinical manifestations included cutaneous (80.6%), cardiovascular (39.2%), respiratory (38.1%), and gastrointestinal (13.1%) symptoms. Portable epinephrine auto-injectors were prescribed to 12.1% of the patients. Subject positive to both vespid and honeybee showed more severe symptoms and higher epinephrine use (P<0.05). The severity was significantly associated with older age, but not with gender, underlying allergic disease, or family history. Apitherapy-induced anaphylaxis showed a higher rate of hospitalization and epinephrine use than bee sting anaphylaxis (P<0.05). CONCLUSION: Vespid is the most common cause of bee venom anaphylaxis in Korea. It is suggested that positivity to honeybee and vespid may be associated with more severe symptoms.
Adult* ; Anaphylaxis* ; Apitherapy ; Bee Venoms ; Bees ; Bites and Stings ; Diagnosis ; Epinephrine ; Hospitalization ; Humans ; Hymenoptera* ; Korea ; Medical Records ; Retrospective Studies* ; Risk Factors ; Venoms*

BACKGROUND: Staphylococcus aureus is a major bacteremia-causing pathogen in hemodialysis patients, frequently colonizing patient skin and mucosa. Active infection control is necessary to prevent methicillin-resistant S. aureus (MRSA) infection in hospitals; however, the spread of community-associated MRSA has recently become a concern for MRSA infection control. We evaluated the nasal colonization of MRSA among hemodialysis patients and the molecular characterization of the MRSA isolates. METHODS: Nasal swabs were obtained from 482 hemodialysis patients in 7 nationwide hospitals in November 2009, and cultured for MRSA colonization. Swabs were inoculated and cultured in 6.5% NaCl tryptic soy broth, then subcultured on MRSASelect medium (Bio-Rad, Hercules, CA) for 20-24 h. Multiplex PCR was performed to analyze staphylococcal cassette chromosome mec (SCCmec) types of MRSA isolates. RESULTS: Of 482 hemodialysis patients, 57 (11.8%) carried MRSA, ranging from 6.7% to 19.0%. Among the 57 MRSA isolates, we identified 3 (5.3%) SCCmec II, 1 (1.8%) SCCmec IIA, 30 (52.6%) SCCmec IIB, 1 (1.8%) SCCmec III, 6 (10.5%) SCCmec IV, and 16 (28.1%) SCCmec IVA subtypes. CONCLUSION: The MRSA carriage rate (11.8%) of hemodialysis patients in this study was high. The SCCmec IIB subtype, a healthcare-associated strain, was the predominant strain, although SCCmec IV isolates, typically found in community-associated MRSA infections, were also frequently observed. To prevent healthcare-associated MRSA infections in hemodialysis patients, standardized infection control measures should be performed, and efforts to reduce MRSA carriage rates should be considered.
Colon* ; Humans ; Infection Control ; Methicillin Resistance* ; Methicillin-Resistant Staphylococcus aureus* ; Mucous Membrane ; Multiplex Polymerase Chain Reaction ; Renal Dialysis* ; Skin ; Staphylococcus aureus

OBJECTIVE: To translate the English version of the Pain Disability Questionnaire (PDQ) into Korean and to investigate the reliability and validity of the Korean version of the PDQ (K-PDQ) in patients suffering chronic disabling musculoskeletal disorders (CDMDs). METHODS: The English version of the PDQ was translated into Korean. Ten patients with CDMDs were randomly selected for a pilot study to assess the comprehensibility of the pre-final version. One hundred and thirty-nine patients suffering from CDMDs for more than 3 months were enrolled in this study. Follow-up questionnaires were obtained to examine the test-retest reliability. Concurrent validity was evaluated by comparing the K-PDQ with the visual analogue scale (VAS). Construct validity was evaluated by comparing the K-PDQ with the brief form of the World Health Organization quality of life assessment instrument (WHOQOL-BREF) using Pearson correlation coefficient. Reliability was assessed using the intraclass correlation coefficient (ICC), and internal consistency was determined by Cronbach's alpha. RESULTS: Test-retest reliability was assessed in 70 patients, with an average time interval of 12 days. The ICC was 0.958 (p<0.001). Internal consistency reached Cronbach's alpha of 0.933 for the functional component and 0.870 for the psychosocial component. The correlation coefficient for the K-PDQ when compared with the VAS was 0.834 in the first assessment and 0.831 in the second assessment. All domains of the WHOQOL-BREF showed a significant negative correlation with the K-PDQ. CONCLUSION: The K-PDQ is a reliable and valid instrument for measuring disability and can be used to assess disability and treatment outcomes in Korean patients with CDMD.
Follow-Up Studies ; Humans ; Pilot Projects ; Quality of Life ; Reproducibility of Results* ; Treatment Outcome ; World Health Organization ; Surveys and Questionnaires

BACKGROUND: As a leading cause of death in Korea, cancer is known to be related to lifestyle including diet. In 2007, the World Cancer Research Fund announced 10 evidence-based guidelines for reducing the number of cancers. The purpose of this paper was to produce guidelines specific to and relevant to the people of Korea. METHODS: Ranging over 6 categories, 15 dietary factors known to be associated with cancers were selected after reviewing the results of relevant researches including Korean subjects and evidence-based research documents regarding the relationships between cancer and diet. The levels of intake of these selected dietary factors by Koreans were compared to the established dietary guidelines and detailed practices for cancer prevention. RESULTS: The Korean dietary guidelines for cancer prevention consists of 8 detailed recommendations along with multiple specific practices based on the analyses of data and documents on weight and intake of cereals, fruits, vegetables, meat, salt, dairy products, alcohol, and nutrient supplements. CONCLUSIONS: The Korean dietary guidelines for cancer prevention were established based on valid scientific approach by analyzing the most recent available data. For some dietary factors, however, sufficient analysis for intake levels in Koreans was not possible. Therefore, fundamental data for the establishment of national strategy and for guideline amendments for preventing cancers need to be gathered through the analyses of relationships between cause and deaths due to cancer, database reinforcement, additional research including Korean subjects, and assessment of usual intake.
Cause of Death ; Edible Grain ; Dairy Products ; Diet ; Financial Management ; Fruit ; Korea ; Life Style ; Meat ; Nutrition Policy ; Reinforcement (Psychology) ; Vegetables

Primary neoplasm of the heart is rare. Benign tumors, the majority of which are myxomas, comprise up to 50% of cardiac neoplasms. Although cardiac myxoma is a source of emboli to the central nervous system and elsewhere in the vascular tree, its clinical signs and symptoms may be nonspecific. These nonspecific systemic symptoms and minor embolic phenomena may be overlooked in patients without a previous history of cardiac problems. Thus, we need to recognize the signs of myxoma and begin treatment immediately. We encountered a case of left atrial myxoma, presenting as pulmonary interstitial edema of unknown cause, in a 50-year-old female patient. Excision of a mass located on the left atrium was scheduled but she developed a cerebral embolism that led to her death.
Central Nervous System ; Edema ; Female ; Heart ; Heart Atria ; Heart Neoplasms ; Humans ; Intracranial Embolism ; Middle Aged ; Myxoma ; Pulmonary Edema