PURPOSE: Dickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents. In this study, we developed a cyclized oligopeptide against DKK1-low density lipoprotein receptor-related protein (LRP) 5/6 interaction and tested the effects of the oligopeptide on tumor burden. MATERIALS AND METHODS: A cyclized oligopeptide based on DKK1-LRP5/6 interactions was synthesized chemically, and its nuclear magnetic resonance structure was assessed. Luciferase reporter assay and mRNA expressions of osteoblast markers were evaluated after oligopeptide treatment. MOPC315.BM.Luc cells were injected into the tail vein of mice, after which cyclized oligopeptide was delivered subcutaneously 6 days a week for 4 weeks. RESULTS: The cyclized oligopeptide containing NXI motif bound to the E1 domain of LRP5/6 effectively on surface plasmon resonance analysis. It abrogated the Wnt-β-catenin signaling inhibited by DKK1, but not by sclerostin, dose dependently. RT-PCR and alkaline phosphatase staining showed increased expressions of osteoblast markers according to the treatment concentrations. Bioluminescence images showed that the treatment of cyclized oligopeptide reduced tumor burden more in oligopeptide treated group than in the vehicle group. CONCLUSION: The cyclized oligopeptide reported here may be another option for the treatment of tumor burden in multiple myeloma.
Alkaline Phosphatase ; Animals ; Bone Density Conservation Agents ; Bone Marrow ; Lipoproteins ; Luciferases ; Magnetic Resonance Spectroscopy ; Mice* ; Multiple Myeloma* ; Osteoblasts ; Plasma ; RNA, Messenger ; Surface Plasmon Resonance ; Tail ; Tumor Burden* ; Veins

BACKGROUND AND OBJECTIVES: The correlations between plaque characteristics and plaque rupture location according to segmental lesion analysis have not been well defined. The aim of this study was to assess those characteristics of ST-segment elevation myocardial infarction (STEMI) culprit lesions according to segmental lesion geometry using virtual histology intravascular ultrasound (VH-IVUS). METHODS: Sixty single discrete lesions found in the left anterior descending (LAD) coronary arteries of 60 patients with STEMI were included. Each lesion was divided into 3 segments based on lumen area (LA) index, calculated by dividing the lesion LA by the reference LA. RESULTS: Among the 3 segments, the mid-segment showed the highest proportion of necrotic core (NC; proximal, mid-, and distal segments: 20.9±11.8%, 22.7±11.3%, and 17.5±11.2%, respectively, p=0.044). VH-IVUS-derived thin-cap fibroatheroma (VH-TCFA) was also more frequently found in the mid-segment than in proximal and distal segments (36.7%, 58.3%, and 16.7%, p < 0.001). The mid-segment also showed the highest prevalence of plaque rupture (45.0%, 78.3% and 11.7%, p < 0.001) and thrombus (61.7%, 95.0%, and 41.7%, p < 0.001) compared to proximal or distal segments. When the lesions were divided into 2 groups according to the median value (4.0 mm2) of minimum lumen area (MLA), plaque rupture at the distal segment was observed only in high MLA lesions (23.3% vs. 0.0%, p=0.011). CONCLUSION: Analysis of longitudinal lesion geometry using the LA index can be useful in evaluating plaque vulnerability and the incidence of plaque rupture and thrombus in STEMI patients.
Coronary Artery Disease ; Coronary Vessels ; Diagnostic Imaging ; Humans ; Incidence ; Myocardial Infarction* ; Plaque, Atherosclerotic ; Prevalence ; Rupture ; Thrombosis ; Ultrasonography

OBJECTIVE: The suicide rate in South Korea was the second highest among the Organization for Economic Cooperation and Development countries in 2017. The purpose of this study is to understand the characteristics of people who died by suicide in Korea from 2013–2017 and to better prevent suicide. METHODS: This study was performed by the Korea Psychological Autopsy Center (KPAC), an affiliate of the Korea Ministry of Health and Welfare. According to the Korea National Statistical Office, the number of suicide victims nationwide was estimated to reach about 70,000 from 2013 to 2017. Comprehensive suicide records from all 254 police stations in South Korea were evaluated by 32 investigators who completed a 14-day didactic training program. Then, we evaluated the characteristics of suicide victims in association with disease data from the National Health Insurance Database (NHID), which is anonymously linked to personal information of suicide victims. RESULTS: Thirty-one of 254 police stations in the Seoul metropolitan area were analyzed by August 10, 2018. Findings showed that the characteristics of suicide victims differed according to the nature of the region. CONCLUSION: Our results suggest that different strategies and methods are needed to prevent suicide by regional groups.
Anonyms and Pseudonyms ; Autopsy ; Education ; Humans ; Korea ; Methods ; National Health Programs ; Organisation for Economic Co-Operation and Development ; Police ; Research Personnel ; Seoul ; Suicide

Regulation of proper gene expression is important for cellular and organismal survival, maintenance, and growth. Abnormal gene expression, even for a single critical gene, can thwart cellular integrity and normal physiology to cause diseases, aging, and death. Therefore, gene expression profiling serves as a powerful tool to understand the pathology of diseases and to cure them. In this study, the difference in gene expression in Flammulina velutipes was compared between the wild type (WT) mushroom and the mutant one with clogging phenomenon. Differentially expressed transcripts were screened to identify the candidate genes responsible for the mutant phenotype using the DNA microarray analysis. A total of 88 genes including 60 upregulated and 28 downregulated genes were validated using the realtime quantitative PCR analysis. In addition, proteomic differences between the WT and mutant mushroom were analyzed using two–dimensional gel electrophoresis and matrixassisted laser desorption/ionization-time of flight (MALDI-TOF). Interestingly, the genes identified by these genomic and proteomic analyses were involved in stress response, translation, and energy/sugar metabolism, including HSP70, elongation factor 2, and pyruvate kinase. Together, our data suggest that the aberrant expression of these genes attributes to the mutant clogging phenotype. We propose that these genes can be targeted to foster normal growth in F. velutipes.

Purpose: Fear of cancer recurrence (FCR) is a common psychological issue in breast cancer (BC) survivors during early survivorship but whether the same is true among long-term survivors has yet to be empirically evaluated. This study investigated FCR level, its associated factors, and impact on quality of life (QoL) in long-term BC survivors. Materials and Methods: Participants included women diagnosed with BC between 2004 and 2010 at two tertiary hospitals. Survey was conducted in 2020. The study measured FCR with the Fear of Cancer Recurrence Inventory and other patient-reported outcomes, including depression and cancer-related QoL. Logistic regression was used to identify factors associated with FCR, and structural equation modeling was conducted to explore the impact of FCR on other outcomes. Results: Of 333 participants, the mean age at diagnosis was 45.5, and 46% experienced FCR. Age at diagnosis ≤ 45 (adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.51 to 4.60), shorter time since diagnosis (aOR, 1.75, 95% CI, 1.08 to 2.89), and having a history of recurrence (aOR, 2.56; 95% CI, 1.16 to 5.65) was associated with more FCR. FCR was significantly associated with an increased risk of depression (β=0.471, p < 0.001) and negatively impacted emotional functioning (β=–0.531, p < 0.001). In addition, a higher FCR level may impair overall health-related QoL in long-term BC survivors (β=–0.108, p=0.021). Conclusion Ten years after diagnosis, long-term BC survivors still experienced a high level of FCR. Further, the negative impact of FCR on QoL and increased depression risk require an FCR screening and appropriate interventions to enhance long-term BC survivors' QoL.