Mitotic Kinases and p53 Signaling

Mitosis is tightly regulated and any errors in this process often lead to aneuploidy, genomic instability, and tumorigenesis. Deregulation of mitotic kinases is significantly associated with improper cell division and aneuploidy. Because of their importance during mitosis and the relevance to cancer, mitotic kinase signaling has been extensively studied over the past few decades and, as a result, several mitotic kinase inhibitors have been developed. Despite promising preclinical results, targeting mitotic kinases for cancer therapy faces numerous challenges, including safety and patient selection issues. Therefore, there is an urgent need to better understand the molecular mechanisms underlying mitotic kinase signaling and its interactive network. Increasing evidence suggests that tumor suppressor p53 functions at the center of the mitotic kinase signaling network. In response to mitotic spindle damage, multiple mitotic kinases phosphorylate p53 to either activate or deactivate p53-mediated signaling. p53 can also regulate the expression and function of mitotic kinases, suggesting the existence of a network of mutual regulation, which can be positive or negative, between mitotic kinases and p53 signaling. Therefore, deciphering this regulatory network will provide knowledge to overcome current limitations of targeting mitotic kinases and further improve the results of targeted therapy

The relationship of examinees’ individual characteristics and perceived acceptability of smart device-based testing to test scores on the practice test of the Korea Emergency Medicine Technician Licensing Examination

Purpose Smart device-based testing (SBT) is being introduced into the Republic of Korea’s high-stakes examination system, starting with the Korean Emergency Medicine Technician Licensing Examination (KEMTLE) in December 2017. In order to minimize the effects of variation in examinees’ environment on test scores, this study aimed to identify any associations of variables related to examinees’ individual characteristics and their perceived acceptability of SBT with their SBT practice test scores. Methods Of the 569 candidate students who took the KEMTLE on September 12, 2015, 560 responded to a survey questionnaire on the acceptability of SBT after the examination. The questionnaire addressed 8 individual characteristics and contained 2 satisfaction, 9 convenience, and 9 preference items. A comparative analysis according to individual variables was performed. Furthermore, a generalized linear model (GLM) analysis was conducted to identify the effects of individual characteristics and perceived acceptability of SBT on test scores. Results Among those who preferred SBT over paper-and-pencil testing, test scores were higher for male participants (mean± standard deviation [SD], 4.36± 0.72) than for female participants (mean± SD, 4.21± 0.73). According to the GLM, no variables evaluated— including gender and experience with computer-based testing, SBT, or using a tablet PC—showed a statistically significant relationship with the total score, scores on multimedia items, or scores on text items. Conclusion Individual characteristics and perceived acceptability of SBT did not affect the SBT practice test scores of emergency medicine technician students in Korea. It should be possible to adopt SBT for the KEMTLE without interference from the variables examined in this study

Electro-acupuncture at acupoint ST36 reduces inflammation and regulates immune activity in Collagen-Induced Arthritic Mice

This study aimed to investigate the anti-inflammatory, anti-arthritic and immuno-regulatory effects of electro-acupuncture (EA) at ST36 on Collagen-induced arthritis (CIA) in mice. Male DBA/1J mice were divided into five groups: Normal, Control, NR (needle retention), EAI and EAII. All mice except those in the normal group were immunized with Collagen II for arthritis induction. Acupuncture needles were inserted into mice ST36 and electrical currents at a frequency of 2 Hz in a continuous rectangular wave form were conducted through the needles for 15 min, 3 times a week. EA treatments were administered for 5 weeks in the EAI group and for 9 weeks in the EAII group. The mice in the NR group were acupunctured in the same manner as the EA groups and the needles were retained for 15 min without electrical stimulation. CIA incidence analysis, ELISA, histological analysis and FACS analysis were performed to evaluate the effect of EA on CIA. EA at ST36 significantly reduced CIA incidence, IL-6, TNF-a, INF-γ, collagen II antibody, IgG and IgM levels in CIA mice serum and prevented knee joint destruction. EA at ST36 also reduced CD69+/CD3e+ cells and CD11a+/CD19+ cells in CIA mice lymph nodes, and CD11b+/Gr1+ cells in CIA mice knee joints. The ratios of CD3e+ cells to CD19+ cells, and CD8+ cells to CD4+ cells were maintained closer to the normal range in the EA groups as compared with the control group or the NR group. EAII was more effective than EAI throughout all the measurements. The NR was effective as well, though less effective than EA. EA at ST36 may have an anti-inflammatory, anti-arthritic and immuno-regulatory effects on CIA in mice. The effectiveness is stronger when EA starts earlier and is applied longer. Needle retention without electrical stimulation may be effective on CIA as well, however less effective than EA. Electrical stimulation and acupoint ST36 may have synergistic effects on CIA

Anti-inflammatory and Immune-regulatory Effects of Subcutaneous Perillae Fructus Extract Injections on OVA-induced Asthma in Mice

Perillae fructus (perilla seed) is a traditional medicinal herb used to treat bronchial asthma in Oriental medical clinics. ST36 is one of the most widely used acupuncture points, particularly for immune system regulation. Injection of an herbal extract into an acupuncture point (herbal acupuncture) is a therapeutic technique combining both acupuncture and herbal treatment. Perillae fructus extract was injected subcutaneously (Perillae fructus herbal acupuncture; PF-HA) at acupoint ST36 of OVA-induced asthmatic mice. The lung weight, bronchoalveolar fluid (BALF) cell count, the number of CCR3+, CD11b+, CD4+ and CD3e+/CD69+ cells in the lung, and the level of IgE, IL-4, IL-5 and IL-13 in BALF and serum were then measured. RT-PCR was used to measure the mRNA expression of IL-4, IL-5, IL-13 and TNF-α in the lung. Lung sections were analyzed histologically. PF-HA significantly reduced lung weight, the number of inflammatory cells in the lung and BALF, the levels of IgE and Th2 cytokines in BALF and serum, mRNA expression of Th2 cytokines in the lung, and pathological changes in lung tissue. Our results suggest that PF-HA may have an anti-inflammatory and immune-regulatory effect on bronchial allergic asthma by restoring the Th1/Th2 imbalance in the immune system and suppressing eosinophilic inflammation in airways

Active pulmonary tuberculosis and latent tuberculosis infection among homeless people in Seoul, South Korea: a cross-sectional study

Background : The aim of this study was to determine the prevalence rate of latent TB infection (LTBI) and active TB among homeless in Seoul metropolitan city, South Korea, and to compare the TB burden among homeless people with that of a control group. Methods : The homeless participants were recruited from five sites between October 30, 2009 and April 12, 2010. LTBI was diagnosed through the QuantiFERON(R) TB Gold In-Tube(QFT-GIT) assay and a tuberculin skin test(TST) and, and active PTB was diagnosed based on chest radiography. Results : Among 313 participants, the prevalence of LTBI was 75.9% (95% CI, 71.1-80.8%) and 79.8% (95% CI, 74.9-84.7%) based on a QFT-GIT assay and the TST, respectively, and that of active PTB was 5.8% (95% CI, 3.2-8.3%). The prevalence of LTBI among homeless participants was about five times higher than controls. Also, the age-specific prevalence rate ratio of active PTB was as high as 24.86. Conclusions : The prevalence rate of LTBI as well as active PTB among homeless people was much higher than that of the general population in South Korea. Thus, adequate strategies to reduce the TB burden among homeless people are needed.Peer Reviewe

BRIT1/MCPH1 links chromatin remodelling to DNA damage response

To detect and repair damaged DNA, DNA damage response proteins need to overcome the barrier of condensed chromatin to gain access to DNA lesions1. ATP-dependent chromatin remodeling is one of the fundamental mechanisms used by cells to relax chromatin in DNA repair2–3. However, the mechanism mediating their recruitment to DNA lesions remains largely unknown. BRIT1 (also known as MCPH1) is an early DNA damage response protein that is mutated in human primary microcephaly4–8. We report here a previously unknown function of BRIT1 as a regulator of ATP-dependent chromatin remodeling complex SWI/SNF in DNA repair. Upon DNA damage, BRIT1 increases its interaction with SWI/SNF through the ATM/ATR-dependent phosphorylation on the BAF170 subunit. This increase of binding affinity provides a means by which SWI/SNF can be specifically recruited to and maintained at DNA lesions. Loss of BRIT1 causes impaired chromatin relaxation owing to reduced association of SWI/SNF with chromatin. This explains the decreased recruitment of repair proteins to DNA lesions and reduced efficiency of repair in BRIT1-deficient cells, resulting in impaired survival from DNA damage. Our findings, therefore, identify BRIT1 as a key molecule that links chromatin remodeling with DNA damage response in the control of DNA repair, and its dysfunction contributes to human disease

The Role of Proteomics in the Diagnosis and Treatment of Women's Cancers: Current Trends in Technology and Future Opportunities

Technological and scientific innovations over the last decade have greatly contributed to improved diagnostics, predictive models, and prognosis among cancers affecting women. In fact, an explosion of information in these areas has almost assured future generations that outcomes in cancer will continue to improve. Herein we discuss the current status of breast, cervical, and ovarian cancers as it relates to screening, disease diagnosis, and treatment options. Among the differences in these cancers, it is striking that breast cancer has multiple predictive tests based upon tumor biomarkers and sophisticated, individualized options for prescription therapeutics while ovarian cancer lacks these tools. In addition, cervical cancer leads the way in innovative, cancer-preventative vaccines and multiple screening options to prevent disease progression. For each of these malignancies, emerging proteomic technologies based upon mass spectrometry, stable isotope labeling with amino acids, high-throughput ELISA, tissue or protein microarray techniques, and click chemistry in the pursuit of activity-based profiling can pioneer the next generation of discovery. We will discuss six of the latest techniques to understand proteomics in cancer and highlight research utilizing these techniques with the goal of improvement in the management of women's cancers

Smart device-based testing for medical students in Korea: satisfaction, convenience, and advantages

The aim of this study was to investigate respondents’ satisfaction with smart device-based testing (SBT), as well as its convenience and advantages, in order to improve its implementation. The survey was conducted among 108 junior medical students at Kyungpook National University School of Medicine, Korea, who took a practice licensing examination using SBT in September 2015. The survey contained 28 items scored using a 5-point Likert scale. The items were divided into the following three categories: satisfaction with SBT administration, convenience of SBT features, and advantages of SBT compared to paper-and-pencil testing or computer-based testing. The reliability of the survey was 0.95. Of the three categories, the convenience of the SBT features received the highest mean (M) score (M= 3.75, standard deviation [SD]= 0.69), while the category of satisfaction with SBT received the lowest (M= 3.13, SD= 1.07). No statistically significant differences across these categories with respect to sex, age, or experience were observed. These results indicate that SBT was practical and effective to take and to administer