Analysis of national surveillance of respiratory pathogens for community-acquired pneumonia in children and adolescents.

BACKGROUND: Respiratory infections among children, particularly community-acquired pneumonia (CAP), is a major disease with a high frequency among outpatient and inpatient visits. The causes of CAP vary depending on individual susceptibility, the epidemiological characteristics of the community, and the season. We performed this study to establish a nationwide surveillance network system and identify the causative agents for CAP and antibiotic resistance in Korean children with CAP. METHODS: The monitoring network was composed of 28 secondary and tertiary medical institutions. Upper and lower respiratory samples were assayed using a culture or polymerase chain reaction (PCR) from August 2018 to May 2020. RESULTS: A total of 1023 cases were registered in patients with CAP, and PCR of atypical pneumonia pathogens revealed 422 cases of M. pneumoniae (41.3%). Respiratory viruses showed a positivity rate of 65.7% by multiplex PCR test, and human rhinovirus was the most common virus, with 312 cases (30.5%). Two hundred sixty four cases (25.8%) were isolated by culture, including 131 cases of S. aureus (12.8%), 92 cases of S. pneumoniae (9%), and 20 cases of H. influenzae (2%). The cultured, isolated bacteria may be colonized pathogen. The proportion of co-detection was 49.2%. The rate of antibiotic resistance showed similar results as previous reports. CONCLUSIONS: This study will identify the pathogens that cause respiratory infections and analyze the current status of antibiotic resistance to provide scientific evidence for management policies of domestic respiratory infections. Additionally, in preparation for new epidemics, including COVID-19, monitoring respiratory infections in children and adolescents has become more important, and research on this topic should be continuously conducted in the future.

Kazinol-E is a specific inhibitor of ERK that suppresses the enrichment of a breast cancer stem-like cell population.

Growing evidence shows that cancer stem-like cells (CSLCs) contribute to breast cancer recurrence and to its resistance to conventional therapies. The extracellular signal-regulated kinase (ERK) signaling pathway is a major determinant in the control of diverse cellular processes, including the maintenance of CSLCs. In this study, we found that Kazinol-E, an antioxidant flavan from Broussonetia kazinoki, decreased the CSLC population of a breast cancer cell line, MCF7. The CSLC population, characterized by CD44 high/CD24 low expression or by high Aldehyde dehydrogenase 1 activity, was decreased by a concentration of Kazinol-E that did not affect the growth of bulk-cultured MCF7 cells. Kazinol-E did not decrease EGF-induced ERK phosphorylation in CSLCs, but did block the phosphorylation of an ERK substrate, p90RSK2, at Thr359/Ser363. We further demonstrated that EGF-induced ERK activity was blocked by Kazinol-E in a wild-type K-Ras-expressing non-small cell lung cancer cell line H226B. An in vitro kinase assay with purified ERK1 and p90RSK2 as its substrate demonstrated a direct inhibition of ERK activity by Kazinol E. Additionally, a the molecular docking study provided putative binding modes of Kazinol-E into the ATP binding pocket of ERK1 Collectively, these results suggest that Kazinol-E is a direct inhibitor of ERK1, and more studies are warranted to develop this reagent for therapeutic breast CSLC targeting.

JNK signaling in hepatocarcinoma cells is associated with the side population upon treatment with anticancer drugs.

Liver cancer is one of the most drug-resistant cancer types, and cancer stem cells are related to drug resistance. c-Jun-N-terminal kinase (JNK) signaling is involved in drug resistance, and the side population of cells (SP cells) can be used as a model to study liver cancer stem cells. We sought to evaluate the relationship between SP cells and JNK signaling in hepatocarcinoma cells. For this purpose, we examined cell proliferation and the SP cell ratio following treatment of Huh7 cells with the anticancer drugs 5-fluorouracil (5-FU) and paclitaxel. The expression of phospho-stress-activated protein kinase (SAPK)/JNK in the treated cells was evaluated using immunoblotting. 5-FU and paclitaxel treatment increased the number of SP cells and JNK phosphorylation, and decreased cell survival. Huh7 and HepG2 cells were also treated with SP600125, a JNK inhibitor, to study the relationship between SP cells and JNK signaling. The increase in the number of SP cells and the SAPK/JNK and c-Jun phosphorylation was reverted by SP600125 treatment in these cells. We also used immunohistochemistry and showed that SAPK/JNK and c-Jun phosphorylation are increased in hepatocarcinoma tissues. In conclusion, our results demonstrate that the number of SP cells and SAPK/JNK phosphorylation are increased upon treatment with anticancer drugs, and that this increase is blocked by inhibition of JNK signaling. These findings suggest that drug resistance in liver cancer may involve an increase in the number of SP cells following JNK activation.

Tussilagone suppresses colon cancer cell proliferation by promoting the degradation of ß-catenin.

Abnormal activation of the Wnt/ß-catenin signaling pathway frequently induces colon cancer progression. In the present study, we identified tussilagone (TSL), a compound isolated from the flower buds of Tussilago farfara, as an inhibitor on ß-catenin dependent Wnt pathway. TSL suppressed ß-catenin/T-cell factor transcriptional activity and down-regulated ß-catenin level both in cytoplasm and nuclei of HEK293 reporter cells when they were stimulated by Wnt3a or activated by an inhibitor of glycogen synthase kinase-3ß. Since the mRNA level was not changed by TSL, proteasomal degradation might be responsible for the decreased level of ß-catenin. In SW480 and HCT116 colon cancer cell lines, TSL suppressed the ß-catenin activity and also decreased the expression of cyclin D1 and c-myc, representative target genes of the Wnt/ß-catenin signaling pathway, and consequently inhibited the proliferation of colon cancer cells. Taken together, TSL might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

[Evaluation of Allergen Specific IgE assay on ADVIA Centaur Immunoassay System.].

BACKGROUND: Allergen specific IgE (sIgE) assay is an important aid in the diagnosis and treatment of allergy. We evaluated the analytical performance of a quantitative chemiluminescence immunoassay for sIgE using the continuous random access ADVIA Centaur. METHODS: Six ADVIA Centaur sIgE reagents for common inhalant allergens in Korea, d1, d2, e1, e5, t3, and t7, were evaluated for precision, dilution recovery (parallelism), comparison with Pharmacia UniCAP sIgE assay and skin prick test, sample volume, and analytical speed according to the NCCLS guidelines (I/LA20-A, EP5-A2). Commercialized positive and negative quality control materials were used for a precision study, and samples from a total of 110 patients were used for dilution recovery and comparison studies. RESULTS: Within-run coefficients of variation (CV) of the 6 items were 3.45-6.14% and within-device CVs (total CVs) of all items were below 10%. Interdilutional CVs of all items were 2.84-11.95%, which showed a good linearity and parallelism over its measuring range. Positive/negative concordance rates of the 6 items with UniCAP sIgE assay were 76.3-96.1% (d1, 88.2%; d2, 96.1%; e1, 91.0%; e5, 77.0%; t3, 90.5%; and t7, 76.3%). Concordance rates of the six items with skin prick test were all above 80%. The quantity of sample volume (25 microL/test) needed was relatively small, and a high throughput (120 tests/hr) and rapid turnaround time (47 min) could be achieved. CONCLUSIONS: The ADVIA Centaur sIgE assay was thought to be a convenient and efficient method to be used in medium- to large-sized laboratories.