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The fusion event between EML4 and ALK drives a significant oncogenic activity in 5% of non-small cell lung cancer (NSCLC). Even though potent ALK-tyrosine kinase inhibitors (ALK-TKIs) are successfully used for the treatment of EML4-ALK-positive NSCLC patients, a subset of those patients eventually acquire resistance during their therapy. Here, we investigate the kinase responses in EML4-ALK V1 and V3-harbouring NSCLC cancer cells after acute inhibition with ALK TKI, lorlatinib (LOR). Using phosphopeptide chip array and upstream kinase prediction analysis, we identified a group of phosphorylated tyrosine peptides including ERBB and AKT proteins that are upregulated upon ALK-TKI treatment in EML4-ALK-positive NSCLC cell lines. Dual inhibition of ALK and ERBB receptors or AKT disrupts RAS/MAPK and AKT/PI3K signalling pathways, and enhances apoptosis in EML4-ALK + NSCLC cancer cells. Heregulin, an ERBB3 ligand, differentially modulates the sensitivity of EML4-ALK cell lines to ALK inhibitors. We found that EML4-ALK cells made resistant to LOR are sensitive to inhibition of ERBB and AKT. These findings emphasize the important roles of AKT and ERBB3 to regulate signalling after acute LOR treatment, identifying them as potential targets that may be beneficial to prevent adaptive resistance to EML4-ALK-targeted therapies in NSCLC.

NEK9 is a key player in the NEK9–EG5 axis for microtubule polymerization, chromosome alignment, and mitosis. In present study, we investigated the altered expression of the NEK9, EG5 and acetyl-α-tubulin as well as common epithelial–mesenchymal transition (EMT) markers (E-cadherin, vimentin, claudin-1, and β-catenin) through the immunohistochemistry analysis of 138 patients with pathologic T3 (pT3) stage colon cancers, and evaluated their metastatic potential. NEK9 expression showed an association with distant metastasis ( P  = 0.032) and was an independent predictive factor for distant metastasis (HR = 3.365, P  < 0.001) by multivariate analysis, which was more significant than either the regional nodal metastasis (HR = 2.496, P  = 0.007) or lymphovascular invasion (HR = 2.090, P  = 0.153). Positive correlations were observed between NEK9 and EG5 or acetyl-α-tubulin (r = 0.236 and P  = 0.007; r = 0.181 and P  = 0.038, respectively) and concordant overexpression of the NEK9–EG5 axis was further confirmed in colon cancer cell lines. These findings collectively suggest that the overexpression of the NEK9–EG5 axis is present and associated with distant metastasis in colon cancer. These biomarkers might be useful for predicting metastatic potential among the patients with pT3 colon cancers.

Mesenchymal stem cells derived from Wharton’s jelly of the umbilical cord (UC-MSCs) have immunomodulatory properties. The aim of this study was to explore whether extracts of MSCs (MSC-Ex) could augment the low therapeutic efficacy of the whole cells in an Aspergillus fumigatus ( Af )-induced atopic dermatitis (AD) model. LPS- or TNF-α/IFN-γ-stimulated keratinocytes (HaCaT cells) were treated with MSC-Ex, and the Af -induced AD model was established in BALB/c mice. In HaCaT cells, MSC-Ex treatment significantly reduced the inflammatory cytokine (IL-6, IL-1β, IL-4, IL-5 and TNF-α), iNOS and NF-κB levels, and upregulated the anti-inflammatory cytokines (IL-10 and TGF-β1). In the AD mice, the MSC-Ex group showed greatly reduced dermatitis, and lower clinical symptom scores and IgE levels. The histological dermatitis scores were also markedly lower in the MSC-Ex-treated animals compared with the MSC-treated group. Decreased levels of IFN-γ (Th1) and IL-17 (Th17), IL-4 and IL-13 (Th2) were detected in T cells and the skin tissue from the MSC-Ex treated AD mice. The therapeutic capacity of MSC-Ex was preserved after lyophilization and reconstitution. MSC-Ex treatment reproducibly suppresses dermatitis and inhibits the induction of inflammatory cytokines in the skin of AD mice. MSC-Ex is therefore a potential new treatment agent for AD.

The oncogenic fusion of EML4-ALK is present in about 4–6% of non-small cell lung cancer (NSCLC). A targeted approach with ALK tyrosine kinase inhibitors (TKIs) has been proven highly effective in ALK-positive NSCLC patients. However, despite the initial responses, the outcome of the treatment is variable. Previous studies have shown that the differential response depends in part on the type of EML4-ALK variant. Here, we examined the combination of ALK inhibitors and microtubule poison, vincristine, in cells expressing EML4-ALK V1 and V3, the two most common variants in NSCLC. We showed that combination therapy of ALK-TKIs with vincristine had anti-proliferative effects and blocked RAS/MAPK, PI3K/AKT and JAK/STAT3 signalling pathways in EML4-ALK V1 but not V3 cells. Our results demonstrate that high levels of tubulin acetylation are associated with poor response to vincristine in EML4-ALK V3 cells. Additionally, we demonstrated differences in microtubule stability between the two EML4-ALK fusions. EML4-ALK V3 cells exhibited dynamic microtubules that confer poor response to vincristine compared to V1 cells. Hence, we suggested that the portion of EML4 in the fusion has an important role for the outcome of the combination treatment.

Although scoring and machine learning methods have been developed to predict patient deterioration, bedside assessment by nurses should not be overlooked. This study aimed to evaluate the performance of subjective bedside assessment of the patient by the rapid response team (RRT) nurses in predicting short-term patient deterioration. Patients noticed by RRT nurses based on the vital sign instability, abnormal laboratory results, and direct contact via phone between November 1, 2016, and December 12, 2017, were included. Five RRT nurses visited the patients according to their shifts and assessed the possibility of patient deterioration. Patient acuity rating (PAR), a scale of 1-7, was used as the tool of bedside assessment. Other scores, including the modified early warning score, VitalPAC early warning score, standardised early warning score, and cardiac arrest risk triage, were calculated afterwards. The performance of these scores in predicting mortality and/or intensive care unit admission within 1 day was compared by calculating the area under the receiver operating curve. A total of 1,426 patients were included in the study, of which 258 (18.1%) died or were admitted to the intensive care unit within 1 day. The area under the receiver operating curve of PAR was 0.87 (95% confidence interval [CI] 0.84-0.89), which was higher than those of modified early warning score (0.66, 95% CI 0.62-0.70), VitalPAC early warning score (0.69, 95% CI 0.66-0.73), standardised early warning score (0.67, 95% CI 0.63-0.70) and cardiac arrest risk triage (0.63, 95% CI 0.59-0.66) (P<0.001). PAR assessed by RRT nurses can be a useful tool for assessing short-term patient prognosis in the RRT setting.

Yeast protein can be a nutritionally suitable auxiliary protein source in livestock food. The breakdown of proteins and thereby generating high-quality peptide, typically provides nutritional benefits. Enzyme hydrolysis has been effectively uesed to generate peptides; however, studies on the potential applications of different types of enzymes to produce yeast protein hydrolysates remain limited. This study investigated the effects of endo- (alcalase and neutrase) and exotype (flavourzyme and prozyme 2000P) enzyme treatments on yeast protein. Endotype enzymes facilitate a higher hydrolysis efficiency in yeast proteins than exotype enzymes. The highest degree of hydrolysis was observed for the protein treated with neutrase, which was followed by alcalase, prozyme 2000P, and flavourzyme. Furthermore, endotype enzyme treated proteins exhibited higher solubility than their exotype counterparts. Notably, the more uniform particle size distribution was observed in endotype treated yeast protein. Moreover, compared with the original yeast protein, the enzymatic protein hydrolysates possessed a higher content of β-sheets structures, indicating their higher structural stability. Regardless of enzyme type, enzyme treated protein possessed a higher total free amino acid content including essential amino acids. Therefore, this study provides significant insights into the production of protein hydrolysates as an alternative protein material.

This study aimed to determine the occurrence rate and risk factors of cardiopulmonary arrest (CPA) during intra-hospital transport (IHT) among critically ill patients, accompanied by a rapid response team (RRT). We performed a retrospective cohort study in a 1300-bed tertiary-care teaching hospital. Data of all admitted patients transported within the hospital and accompanied by the RRT from October 2012 to May 2016 were included. We compared patients with CPA (+) and patients without CPA (-) to identify risk factors for CPA during transport. Among 535 patients, CPA occurred in eight (1.5%) patients during IHT. There were no significant differences in age, sex, and comorbidities between groups. More patients in the CPA (+) group than in the CPA (-) group received manual ventilation during IHT (75% vs. 23.0%, p = 0.001). An increased risk of CPA (p<0.001) corresponded with a higher number of vasopressors used during IHT. In univariate logistic regression analysis, history of myocardial infarction (OR 10.7, 95% CI 2.4-50.5, p = 0.005), manual ventilation (OR 10.1, 95% CI 2.0-50.5, p = 0.005), and use of three or more vasopressors (OR 11.1, 95% CI 2.5-48.9, p = 0.001) were significantly associated with risk of CPA during RRT-led IHT. Despite accompaniment by a specialized team such as the RRT, CPA can occur during IHT. History of myocardial infarction, manual ventilation with bag-valve mask, and the use of three or more vasopressors were independent risk factors of CPA during IHT of critically ill patients accompanied by the RRT.

In this study, the inhibitory effect of corn silk on melanin production was evaluated. This study was performed to investigate the inhibitory effect of corn silk on melanin production in Melan-A cells by measuring melanin production and protein expression. The corn silk extract applied on Melan-A cells at a concentration of 100 ppm decreased melanin production by 37.2% without cytotoxicity. This was a better result than arbutin, a positive whitening agent, which exhibited a 26.8% melanin production inhibitory effect at the same concentration. The corn silk extract did not suppress tyrosinase activity but greatly reduced the expression of tyrosinase in Melan-A cells. In addition, corn silk extract was applied to the human face with hyperpigmentation, and skin color was measured to examine the degree of skin pigment reduction. The application of corn silk extract on faces with hyperpigmentation significantly reduced skin pigmentation without abnormal reactions. Based on the results above, corn silk has good prospects for use as a material for suppressing skin pigmentation.

The recent increase in the number of cases of indigenous hepatitis E virus (HEV) infection highlights the importance of identifying the transmission routes for the prevention of such infections. Presented herein is the first case of acute HEV infection after ingesting wild roe deer meat in South Korea. A 43-year-old male presented with abdominal discomfort and jaundice. He had not recently traveled abroad, but had eaten raw roe-deer meat 6-8 weeks before the presentation. On the 7th day of hospitalization the patient was diagnosed with acute viral hepatitis E. Phylogenetic analysis of his serum revealed genotype-4 HEV. This case supports the possibility of zoonotic transmission of HEV because the patient appears to have been infected with genotype-4 HEV after ingesting raw deer meat.

This study compared the prevalence of hepatitis C virus (HCV) infection in the Republic of Korea and estimated the high-risk regions and towns. National Health Insurance Service data for 8 years from 2005 to 2012 were used. The subjects of the study had visited medical facilities and been diagnosed with or received treatment for acute or chronic HCV as a primary or secondary disease according to ICD-10 codes of B17.1 or B18.2, respectively. Any patient who received treatment for the same disease multiple times during 1 year was counted as one patient in that year. To correct for the effect of the age structure of the population by year and region, the age-adjusted prevalence was calculated using the direct method based on the registered population in 2010. The overall prevalence of HCV infection among Korean adults (>20 years old) increased from 0.14% in 2005 to 0.18% in 2012. The sex-, age-, and region-adjusted prevalence in 2012 was 0.18%. The prevalence was highest in Busan, Jeonnam, and Gyeongnam, and there were towns with noticeably higher prevalences within these regions: Jindo (0.97%) in Jeonnam, Namhae (0.90%) in Gyeongnam, and Seo-gu (0.86%) in Busan. The prevalence of HCV infection differs by regions as well as towns in the Republic of Korea, and is highest in Busan, Jeonnam, and Gyeongnam. The reasons for the high prevalence in these specific regions should be identified, since this could help prevent HCV infections in the future. In addition, active surveillance and treatment policies should be introduced to stop any further spread of infection in these high-prevalence regions.