Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells / 한국유방암학회지

Purpose@#Chromosomal instability (CIN) contributes to intercellular genetic heterogeneity and has been implicated in paclitaxel (PTX) resistance in breast cancer. In this study, we explored polo-like kinase 1 (PLK1) as an important regulator of mitotic integrity and as a useful predictive biomarker for PTX resistance in breast cancer. @*Methods@#We performed PTX resistance screening using the human kinome CRISPR/ Cas9 library in breast cancer cells. In vitro cell proliferation and apoptosis assays and in vivo xenograft experiments were performed to determine the effects of PLK1 on breast cancer cells. Immunofluorescence microscopy was used to measure the degree of multipolar cell division. @*Results@#Kinome-wide CRISPR/Cas9 screening identified various kinases involved in PTX resistance in breast cancer cells; among these, PLK1 was chosen for further experiments.PLK1 knockdown inhibited the proliferation of MDA-MB-231 and MDA-MB-468 cells in vitro and in vivo. Moreover, PLK1 silencing sensitized breast cancer cells and mouse xenograft tumor models to PTX cytotoxicity. Silencing of PLK1 induced the formation of multipolar spindles and increased the percentage of multipolar cells. In addition, PLK1 silencing resulted in the downregulation of BubR1 and Mad2 in breast cancer cells. Furthermore, PLK1 upregulation in primary breast cancer was associated with decreased overall patient survival based on the analysis of The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium databases. @*Conclusion@#PLK1 plays an important role in PTX resistance by regulating CIN in breast cancer cells. Targeting PLK1 may be an effective treatment strategy for PTX-resistant breast cancers.

The National Health Plan 2030: Its Purpose and Directions of Development / 예방의학회지

The National Health Plan 2030 (HP2030) started to be prepared in 2017 and was completed and announced in December 2020. This study presents an overview of how it was established, the major changes in policies, its purpose, and future directions. This study analyzed the steps taken in the past 4 years to establish HP2030 and reviewed major issues at the international and governmental levels based on an evaluation of HP2020 and its content. HP2030 establishes 6 divisions and 28 topic areas, and it will continue to expand investments in health with a total budget of 2.5 trillion Korean won. It also established goals to enhance health equity for the first time, with the goal of calculating healthy life expectancy in a way that reflects the circumstances of Korea and reducing the gap in income and healthy life expectancy between regions. The establishment of HP2030 is significant in that it constitutes a sustainable long-term plan with sufficient preparation, contains policy measures that everyone participates in and makes together, and works towards improvements in universal health standards and health equity. With the announcement of HP2030, which includes goals and directions of the national health policy for the next 10 years, it will be necessary to further strengthen collaboration with relevant ministries, local governments, and agencies in various fields to concretize support for prevention-centered health management as a national task and to develop a health-friendly environment that considers health in all policy areas.

The National Health Plan 2030: Its Purpose and Directions of Development / 예방의학회지

The National Health Plan 2030 (HP2030) started to be prepared in 2017 and was completed and announced in December 2020. This study presents an overview of how it was established, the major changes in policies, its purpose, and future directions. This study analyzed the steps taken in the past 4 years to establish HP2030 and reviewed major issues at the international and governmental levels based on an evaluation of HP2020 and its content. HP2030 establishes 6 divisions and 28 topic areas, and it will continue to expand investments in health with a total budget of 2.5 trillion Korean won. It also established goals to enhance health equity for the first time, with the goal of calculating healthy life expectancy in a way that reflects the circumstances of Korea and reducing the gap in income and healthy life expectancy between regions. The establishment of HP2030 is significant in that it constitutes a sustainable long-term plan with sufficient preparation, contains policy measures that everyone participates in and makes together, and works towards improvements in universal health standards and health equity. With the announcement of HP2030, which includes goals and directions of the national health policy for the next 10 years, it will be necessary to further strengthen collaboration with relevant ministries, local governments, and agencies in various fields to concretize support for prevention-centered health management as a national task and to develop a health-friendly environment that considers health in all policy areas.

Current Status and Needs Assessment for Obesity Prevention and Management Project at Public Health Centers

Purpose@#The obesity prevention and management program led by public health centers are important in the community.This study aims to identify the current status of obesity prevention and management programs at public health centers and perceptions regarding facilitators and barriers when implementing programs. @*Methods@#This study used a concurrent mixed methods design. A survey was conducted to investigate the current status and infrastructure of the obesity prevention and management program at eighty-three public health centers nationwide. Nine program managers and six local residents with experience in the program were interviewed by using a semi-structured questionnaires. @*Results@#Most of the infrastructure facilities for the program were inadequate, and insufficient budgets and lack of professional staff were identified as barriers. Facilitators included diversification of program delivery methods, operator competence, and visible outcomes and rewards. For the effectiveness of the program, it is vital to have adequate assistants, a sufficient budget, various promotional methods, and connections with various institutions in the community. On this basis, it is acknowledged that the public health center serves as a platform for preventing and managing obesity in the community. Conclusion: It is expected that infrastructure improvements in public health centers and the link with community resources are needed. In addition, there is an urgent need to set standards for obesity prevention and management programs implemented in public health centers to ‘resolve regional disparities’.

Policy Directions to Improve Collaboration of Central and Local Government for Effective Health Promotion Policy / 보건행정학회지

The purpose of this study is to analyze the long-term plans of the central and local governments in order to plan policy and implementing programs. Through this, the governments is find out to reduce administrative burden. Based on the national health plan, evidence and related laws were collected and analyzed. As a quantitative methodology analyzed the contents of related laws in the overall plan. The qualitative methodologies analyzed and categorized the planning status of cities and provinces in the plan and were collated. There are a total of 39 plans for long-term plans by laws. The role of the central and local governments in the public health sector, there are a total of four plans (10.3%) that need to establish long-term and annual plans for the central and local (cities, provinces) government. A total of seven plans (17.9%) were required to establish a plan by the only local government. In terms of the public health sector on the local governments, 20 plans (51.3%) by cities and 12 plans (30.8%) by provinces were established by law. And in the health sector should be established 9 plans (40.9%) by cities and 7 plans (31.8%) by provinces. The plan needs to be reformed and merged between plans so that governments can focus on the program through planning central government policies, reducing local government administration.

Agmatine Ameliorates High Glucose-Induced Neuronal Cell Senescence by Regulating the p21 and p53 Signaling

Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes mellitus. Neuronal senescence leads to the secretion of pro-inflammatory cytokines, the production of reactive oxygen species, and the alteration of cellular homeostasis. Agmatine, which is biosynthesized by arginine decarboxylation, has been reported in previous in vitro to exert a protective effect against various stresses. In present study, agmatine attenuated the cell death and the expression of pro-inflammatory cytokines such as IL-6, TNF-alpha and CCL2 in high glucose in vitro conditions. Moreover, the senescence associated-beta-galatosidase's activity in high glucose exposed neuronal cells was reduced by agmatine. Increased p21 and reduced p53 in high glucose conditioned cells were changed by agmatine. Ultimately, agmatine inhibits the neuronal cell senescence through the activation of p53 and the inhibition of p21. Here, we propose that agmatine may ameliorate neuronal cell senescence in hyperglycemia.

Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation

PURPOSE: Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. MATERIALS AND METHODS: This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. RESULTS: Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. CONCLUSION: Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.

Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation

PURPOSE: Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. MATERIALS AND METHODS: This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. RESULTS: Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. CONCLUSION: Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.

miR-Let7A Modulates Autophagy Induction in LPS-Activated Microglia

Microglia regulate the secretion of various immunomediators in central nervous system diseases. Microglial autophagy is the crucial process for cell's survival and cytokine productions. Recent studies have reported that several microRNAs are involved in the autophagy system. miR-Let7A is such a microRNA that plays a role in various inflammation responses, and is magnified as a key modulator particularly in the autophagy system. In present study, we investigated whether miR-Let7A is involved in autophagy in activating microglia. Overexpression of miR-Let7A in LPS-stimulated BV2 microglial cells promoted the induction of the autophagy related factors such as LC3II, Beclin1, and ATG3. Our results suggest a potential role of miR-Let7A in the autophagy process of microglia during CNS inflammation.