To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140 mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca. 10 nm in water was confirmed by dynamic and static light scattering techniques. In a breast cancer mouse model, in vivo biodistribution studies revealed that the ⁶⁴Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents. PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals, while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection, enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.

Background and Objectives: Brain organoids have the potential to improve our understanding of brain development and neurological disease. Despite the importance of brain organoids, the effect of vascularization on brain organoids is largely unknown. The objective of this study is to develop vascularized organoids by assembling vascular spheroids with cerebral organoids. Methods: and Results: In this study, vascularized spheroids were generated from non-adherent microwell culture system of human umbilical vein endothelial cells, human dermal fibroblasts and human umbilical cord blood derived mesenchymal stem cells. These vascular spheroids were used for fusion with iPSCs induced cerebral organoids. Immunostaining studies of vascularized organoids demonstrated well organized vascular structures and reduced apoptosis. We showed that the vascularization in cerebral organoids up-regulated the Wnt/β-catenin signaling. Conclusions We developed vascularized cerebral organoids through assembly of brain organoids with vascular spheroids. This method could not only provide a model to study human cortical development but also represent an opportunity to explore neurological disease.

Purpose: Korea has implemented an early screening for colorectal cancer since 2004. However, it is not known whether this has translated into improved survival over the years. Methods: We acquired colorectal cancer mortality data from the Cause of Death Statistics in Korea from 2000 to 2020. We characterized the data into year of death, cancer-specific loci, and age group. We analyzed age-standardized mortality rates (ASMR) according to year of death, age group, and primary location to find trends in colorectal cancer mortality over a 20-year period. Results: The crude mortality rate of colorectal cancer increased from 8.78 per 100,000 in 2000 to 17.27 per 100,000 in 2020. The second decade was slower in increments compared to the first decade. ASMR showed a decrease over the second decade after an initial increase in the first decade. The decrease was primarily from the lowering of ASMR for rectosigmoid cancers. Age group analysis showed a lowering of ASMR mainly in the 45–59-year, 60–74-year, and ≥ 75-year age groups; however, 0–29-year and 30–44-year age groups showed generally unchanged ASMR over the total period. Conclusion After a brief incline of age-specific mortality of colorectal cancers during the early 2000s, colorectal cancer mortality has gradually been decreasing in the past decade. This was mainly due to decreased mortalities in rectosigmoid colon cancers especially in the age groups that were the target of early screening.

This study aimed to identify maternal, infant, and perinatal mortality using the nationalpopulation data of South Korea between 2018 and 2020, and to analyze mortality rates according tocharacteristics such as age, date of death, and cause of death in each group. This study updates themost recent study using 2009 to 2017 data.Methods: Analyses of maternal, infant, and perinatal mortality were done with data identifiedthrough the supplementary investigation system for cases of death from the Census of PopulationDynamics data provided by Statistics Korea from 2018 to 2020.Results: Between 2018 and 2020, a total of 99 maternal deaths, 2,427 infant deaths, and 2,408 perinatal deaths were identified from 901,835 live births. The maternal mortality ratio was 11.3 deathsper 100,000 live births in 2018; it decreased to 9.9 in 2019 but increased again to 11.8 in 2020. Thematernal mortality ratio increased steeply in women over the age of 40 years. An increasing trend inthe maternal mortality ratio was found for complications related to the puerperium and hypertensive disorders. Both infant and perinatal mortality continued to decrease, from 2.8 deaths per 1,000live births in 2018 to 2.5 in 2020 and from 2.8 in 2018 to 2.5 in 2020, respectively.Conclusion: Overall, the maternal, infant, and perinatal mortality statistics showed improvements.However, more attention should be paid to women over 40 years of age and specific causes of maternal deaths, which should be taken into account in Korea’s maternal and child health policies.

Objective: Suicide is a huge nationwide problem that incurs a lot of socio-economic costs. Suicide also inflicts severe distress on the people left behind. The government of the Republic of Korea has been making many policy efforts to reduce suicide rate. The gatekeeper program, ‘Suicide CARE’, is one of the meaningful modalities for preventing suicide. Methods: Multidisciplinary research team collaborated to update the ‘Suicide CARE’ to version 2.0. Results: In the ‘Introductory part’, the authors have the time to think about the necessity and significance of the program before conducting full-scale gatekeeper training. In the ‘Careful observation’ part, trainees learn how to understand and recognize the various linguistic, behavioral, and situational signals that a person shows before committing suicide. In the ‘Active listening’ part, trainees learn how to ask suicide with a value-neutral attitude as well listening empathetically. In the ‘Risk evaluation and Expert referral’ part, trainees learn intervening strategies to identify a person’s suicidal intention, plan, and past suicide attempts, and connect the person to appropriate institutes or services. Conclusion Subsequent studies should be conducted to verify the efficacy of the gatekeeper program.

Objective: In 2011, “Suicide CARE” (Standardized Suicide Prevention Program for Gatekeeper Intervention in Korea) was originally developed for the early detection of warning signs of suicide completion, since there is a tendency to regard emotional suppression as a virtue of Korean traditional culture. A total of 1.2 million individuals completed the training program of “Suicide CARE” in Korea. Methods: More sophisticated suicide prevention approaches according to age, sex, and occupation have been proposed, demanding for a more detailed revision of “Suicide CARE.” Thus, during the period from August 2019 to February 2020, “Suicide CARE” has been updated to version 2.0. The assessments on domestic gatekeeper training programs for suicide prevention, international gatekeeper training programs for suicide prevention, psychological autopsy interview reports between 2015 and 2018, and the evaluation of feedback from people who completed “Suicide CARE” version 1.6 training were performed. Results: We describe the revision process of “Suicide CARE,” revealing that “Suicide CARE” version 2.0 has been developed using an evidence-based methodology. Conclusion It is expected that “Suicide CARE” version 2.0 be positioned as the basic framework for many developing gatekeeper training programs for suicide prevention in Korea in the near future.

PURPOSE: We evaluated the relationship of cancer-associated fibroblasts (CAFs) and desmoplastic reactions with cancer invasiveness and long-term outcomes in patients with colorectal cancer (CRC). METHODS: Histologic evaluation of mature CAFs and desmoplasia was performed by observing the collagen fiber structure and fibroblast cytomorphology in the intratumoral stroma and invasive front of CRC tissues. Cancer-cell invasiveness was evaluated using lymphatic invasion, vascular invasion, perineural invasion, tumor budding, and tumor growth patterns. Overall survival and systemic recurrence were analyzed. A network analysis was performed between CAF maturation, desmoplastic reaction, and cancer invasiveness. RESULTS: The proportions of mature CAFs in the intratumoral stroma and the invasive front were 57.6% and 60.3%, respectively. Epidermal growth factor receptor (EGFR) overexpression was significantly higher in the mature CAFs in the invasive front as compared to immature CAFs. Lymphatic invasion increased as the number of mature fibroblasts in the intratumoral stroma increased. Tumor budding was observed in almost half of both mature and immature stroma samples and occurred more frequently in infiltrating tumors. On network analysis, well-connected islands were identified that was associated with EGFR overexpression, CAF maturation, and infiltrating tumor growth patterns leading to tumor budding. CONCLUSION: The maturity of CAFs and desmoplastic reactions were associated with cancer invasion. However, the cytomorphologic characteristics of CAFs were insufficient as an independent prognostic factor for patients with CRC.
Collagen ; Colorectal Neoplasms ; Fibroblasts ; Humans ; Islands ; Receptor, Epidermal Growth Factor ; Recurrence ; Wound Healing

Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn2+) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn2+ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn2+ levels are largely regulated by metallothioneins (MTs), Zn2+ importers (ZIPs), and Zn2+ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn2+. However, these regulatory actions of Zn2+ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn2+ levels, Zn2+-mediated signal transduction, impacts of Zn2+ on ion channels and mitochondrial metabolism, and finally, the implications of Zn2+ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn2+.
Central Nervous System ; Heart ; Immune System ; Ion Channels ; Mammary Glands, Human ; Metabolism ; Metallothionein ; Oxidation-Reduction ; Pancreas ; Prostate ; Protein Conformation ; Signal Transduction ; Zinc*

Cardiac hypertrophy contributes an increased risk to major cerebrovascular events. However, the molecular mechanisms underlying cerebrovascular dysfunction during cardiac hypertrophy have not yet been characterized. In the present study, we examined the molecular mechanism of isoproterenol (ISO) -evoked activation of Ras/Raf/MAPK pathways as well as PKA activity in cerebral artery of rabbits, and we also studied whether the activations of these signaling pathways were altered in cerebral artery, during ISO-induced cardiac hypertrophy compared to heart itself. The results show that the mRNA level of c-fos (not c-jun and c-myc) in heart and these genes in cerebral artery were considerably increased during cardiac hypertrophy. These results that the PKA activity and activations of Ras/Raf/ERK cascade as well as c-fos expression in rabbit heart during cardiac hypertrophy were consistent with previous reports. Interestingly, however, we also showed a novel finding that the decreased PKA activity might have differential effects on Ras and Raf expression in cerebral artery during cardiac hypertrophy. In conclusion, there are differences in molecular mechanisms between heart and cerebral artery during cardiac hypertrophy when stimulated with beta2 adrenoreceptor (AR), suggesting a possible mechanism underlying cerebrovascular dysfunction during cardiac hypertrophy.
Cardiomegaly* ; Cerebral Arteries* ; Heart* ; Isoproterenol ; Rabbits ; RNA, Messenger