DNA methylation is a relatively stable epigenetic modification that can regulate and stabilize gene expression patterns and hence establish cell identity. Because metabolic intermediates are key factors of DNA methylation and demethylation, perturbations in metabolic homeostasis can trigger alterations in cell-specific patterns of DNA methylation and contribute to disease development, including type 2 diabetes (T2D). During the past decade, genome-wide DNA methylation studies of T2D have expanded our knowledge of the molecular mechanisms underlying T2D. This review summarizes case-control studies of the DNA methylome of T2D and discusses DNA methylation as both a cause and consequence of T2D. Therefore, DNA methylation has potential as a promising T2D biomarker that can be applied to the development of therapeutic strategies for T2D.
Case-Control Studies ; DNA Methylation ; DNA ; Epigenomics ; Gene Expression ; Homeostasis

DNA methylation is a relatively stable epigenetic modification that can regulate and stabilize gene expression patterns and hence establish cell identity. Because metabolic intermediates are key factors of DNA methylation and demethylation, perturbations in metabolic homeostasis can trigger alterations in cell-specific patterns of DNA methylation and contribute to disease development, including type 2 diabetes (T2D). During the past decade, genome-wide DNA methylation studies of T2D have expanded our knowledge of the molecular mechanisms underlying T2D. This review summarizes case-control studies of the DNA methylome of T2D and discusses DNA methylation as both a cause and consequence of T2D. Therefore, DNA methylation has potential as a promising T2D biomarker that can be applied to the development of therapeutic strategies for T2D.

DNA methylation is a stable epigenetic mark that can be inherited through multiple cell divisions. During development and cell differentiation, DNA methylation is dynamic, but some DNA methylation patterns may be retained as a form of epigenetic memory. DNA methylation profiles can be useful for the lineage classification and quality control of stem cells such as embryonic stem cells, induced pluripotent cells and mesenchymal stem cells. During cancer initiation and progression, genome-wide and gene-specific DNA methylation changes occur as a consequence of mutated or deregulated chromatin regulators. Early aberrant DNA methylation states occurring during transformation appear to be retained during tumor evolution. Similarly, DNA methylation differences among different regions of a tumor reflect the history of cancer cells and their response to the tumor microenvironment. Therefore, DNA methylation can be a useful molecular marker for cancer diagnosis and drug treatment.
Cell Differentiation ; Cell Division ; Chromatin ; Classification ; Diagnosis ; DNA Methylation* ; DNA* ; Embryonic Stem Cells ; Epigenomics* ; Memory* ; Mesenchymal Stromal Cells ; Quality Control ; Stem Cells ; Tumor Microenvironment

The funding acknowledgment in this article was partially omitted as published.

MicroRNAs (miRNAs) have been demonstrated to play an important role in carcinogenesis. Previous studies revealed that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. In this study, we measured the plasma expression levels of three miRNAs (miR-21, miR-27a, and miR-155) to investigate the usefulness of miRNAs for gastric cancer detection. We initially examined plasma miRNA expression levels in a screening cohort consisting of 15 patients with gastric cancer and 15 healthy controls from Korean population, using TaqMan quantitative real-time polymerase chain reaction. We observed that the expression level of miR-27a was significantly higher in patients with gastric cancer than in healthy controls, whereas the miR-21 and miR-155a expression levels were not significantly higher in the patients with gastric cancer. Therefore, we further validated the miR-27a expression level in 73 paired gastric cancer tissues and in a validation plasma cohort from 35 patients with gastric cancer and 35 healthy controls. In both the gastric cancer tissues and the validation plasma cohort, the miR-27a expression levels were significantly higher in patients with gastric cancer. Receiver-operator characteristic (ROC) analysis of the validation cohort, revealed an area under the ROC curve value of 0.70 with 75% sensitivity and 56% specificity in discriminating gastric cancer. Thus, the miR-27a expression level in plasma could be a useful biomarker for the diagnosis and/or prognosis of gastric cancer.
Carcinogenesis ; Cohort Studies ; Diagnosis ; Humans ; Mass Screening ; MicroRNAs ; Plasma ; Prognosis ; Real-Time Polymerase Chain Reaction ; Ribonucleases ; ROC Curve ; Sensitivity and Specificity ; Stomach Neoplasms*

Background: The coronavirus disease 2019 (COVID-19) pandemic began in December 2019.While it has not yet ended, COVID-19 has already created transitions in health care, one of which is a decrease in medical use for health-related issues other than COVID-19 infection.Korean soldiers are relatively homogeneous in terms of age and physical condition. They show a similar disease distribution pattern every year and are directly affected by changes in government attempts to control COVID-19 with nonpharmaceutical interventions. This study aimed to identify the changes in patterns of outpatient visits and admissions to military hospitals for a range of disease types during a pandemic. Methods: Outpatient attendance and admission data from all military hospitals in South Korea from January 2016 to December 2020 were analyzed. Only active enlisted soldiers aged 18–32 years were included. Outpatient visits where there was a diagnosis of pneumonia, acute upper respiratory tract infection, infectious conjunctivitis, infectious enteritis, asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, urticaria, and fractures were analyzed. Admissions for pneumonia, acute enteritis, and fractures were also analyzed. All outpatient visits and admissions in 2020 for each disease were counted on a weekly basis and compared with the average number of visits over the same period of each year from 2016 to 2019. The corrected value was calculated by dividing the ratio of total weekly number of outpatient visits or admissions to the corresponding medical department in 2020 to the average in 2016–2019. Results: A total of 5,813,304 cases of outpatient care and 143,022 cases of admission were analyzed. For pneumonia, the observed and corrected numbers of outpatient visits and admissions in 2020 decreased significantly compared with the average of other years (P < 0.001). The results were similar for outpatient visits for acute upper respiratory tract infection and infectious conjunctivitis (P < 0.001), while the corrected number of outpatient visits for infectious enteritis showed a significant increase in 2020 (P = 0.005). The corrected number of outpatient visits for asthma in 2020 did not differ from the average of the previous 4 years but the number of visits for the other allergic diseases increased significantly (P < 0.001). For fractures, the observed and corrected numbers of outpatient visits and admissions in 2020 decreased significantly compared with the average of other years (P < 0.001). Conclusion During the COVID-19 pandemic, outpatient visits to military hospitals for respiratory and conjunctival infections and fractures decreased, whereas visits for allergic diseases did not change or increased only slightly. Admissions for pneumonia decreased significantly in 2020, while those for acute enteritis and fractures also decreased, but showed an increased proportion compared with previous years. These results are important because they illustrate the changing patterns in lifestyle as a result of public encouragement to adopt nonpharmaceutical interventions during the pandemic and their effect on medical needs for both infectious and noninfectious diseases in a select group.

Background: The coronavirus disease 2019 (COVID-19) pandemic began in December 2019.While it has not yet ended, COVID-19 has already created transitions in health care, one of which is a decrease in medical use for health-related issues other than COVID-19 infection.Korean soldiers are relatively homogeneous in terms of age and physical condition. They show a similar disease distribution pattern every year and are directly affected by changes in government attempts to control COVID-19 with nonpharmaceutical interventions. This study aimed to identify the changes in patterns of outpatient visits and admissions to military hospitals for a range of disease types during a pandemic. Methods: Outpatient attendance and admission data from all military hospitals in South Korea from January 2016 to December 2020 were analyzed. Only active enlisted soldiers aged 18–32 years were included. Outpatient visits where there was a diagnosis of pneumonia, acute upper respiratory tract infection, infectious conjunctivitis, infectious enteritis, asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, urticaria, and fractures were analyzed. Admissions for pneumonia, acute enteritis, and fractures were also analyzed. All outpatient visits and admissions in 2020 for each disease were counted on a weekly basis and compared with the average number of visits over the same period of each year from 2016 to 2019. The corrected value was calculated by dividing the ratio of total weekly number of outpatient visits or admissions to the corresponding medical department in 2020 to the average in 2016–2019. Results: A total of 5,813,304 cases of outpatient care and 143,022 cases of admission were analyzed. For pneumonia, the observed and corrected numbers of outpatient visits and admissions in 2020 decreased significantly compared with the average of other years (P < 0.001). The results were similar for outpatient visits for acute upper respiratory tract infection and infectious conjunctivitis (P < 0.001), while the corrected number of outpatient visits for infectious enteritis showed a significant increase in 2020 (P = 0.005). The corrected number of outpatient visits for asthma in 2020 did not differ from the average of the previous 4 years but the number of visits for the other allergic diseases increased significantly (P < 0.001). For fractures, the observed and corrected numbers of outpatient visits and admissions in 2020 decreased significantly compared with the average of other years (P < 0.001). Conclusion During the COVID-19 pandemic, outpatient visits to military hospitals for respiratory and conjunctival infections and fractures decreased, whereas visits for allergic diseases did not change or increased only slightly. Admissions for pneumonia decreased significantly in 2020, while those for acute enteritis and fractures also decreased, but showed an increased proportion compared with previous years. These results are important because they illustrate the changing patterns in lifestyle as a result of public encouragement to adopt nonpharmaceutical interventions during the pandemic and their effect on medical needs for both infectious and noninfectious diseases in a select group.

The spatiotemporal regulation of immune cells in lymph nodes (LNs) is crucial for mounting protective T-cell responses, which are orchestrated by dendritic cells (DCs). However, it is unclear how the DC subsets are altered by the inflammatory milieu of LNs. Here, we show that the inflamed LNs of Listeria-infected mice are characterized by the clustering of neutrophils and monocytes and IFN-γ production. Significantly, the early inflammatory responses are coupled with the differentiation of not one, but two types of CD64⁺CD11c⁺MHCII⁺ inflammatory DCs. Through the assessment of chemokine receptor dependency, gene expression profiles, growth factor requirements and DC-specific lineage mapping, we herein unveil a novel inflammatory DC population (we termed ‘CD64⁺ cDCs’) that arises from conventional DCs (cDCs), distinguishable from CD64⁺ monocyte-derived DCs (moDCs) in inflamed LNs. We determined that Listeria-induced type I IFN is a critical inflammatory cue for the development of CD64⁺ cDCs but not CD64⁺ moDCs. Importantly, CD64⁺ cDCs displayed a higher potential to activate T cells than CD64⁺ moDCs, whereas the latter showed more robust expression of inflammatory genes. Although CD64⁺ and CD64− cDCs were able to cross-present soluble antigens at a high dose to CD8⁺ T cells, CD64⁺ cDCs concentrated and cross-presented a minute amount of soluble antigens delivered via CD64 (FcγRI) as immune complexes. These findings reveal the role of early inflammatory responses in driving the differentiation of two inflammatory DC subsets empowered with distinct competencies.

OBJECTIVE: Retrospective analysis to compare the effect and complication of epidural patient-controlled analgesia (epidural PCA) with intravenous patient-controlled analgesia (IV PCA) for the treatment of the post-operative pain after posterior lumbar instrumented fusion. METHODS: Sixty patients who underwent posterior lumbar instrumented fusion for degenerative lumbar disease at our institution from September 2007 to January 2008 were enrolled in this study. Out of sixty patients, thirty patients received IV PCA group and thirty patients received epidural PCA group. The pain scale was measured by the visual analogue scale (VAS) score. RESULTS: There were no significant difference between IV PCA group and epidural PCA group on the PCA related complications (p=0.7168). Ten patients in IV PCA group and six patients in epidural PCA group showed PCA related complications. Also, there were no significant differences in reduction of VAS score between two groups on postoperative 2 hours (p=0.9618) and 6 hours (p=0.0744). However, postoperative 12 hours, 24 hours and 48 hours showed the significant differences as mean of reduction of VAS score (p=0.0069, 0.0165, 0.0058 respectively). CONCLUSION: The epidural PCA is more effective method to control the post-operative pain than IV PCA after 12 hours of spinal fusion operation. However, during the first twelve hours after operation, there were no differences between IV PCA and epidural PCA.
Analgesia, Patient-Controlled* ; Humans ; Pain, Postoperative ; Passive Cutaneous Anaphylaxis ; Retrospective Studies ; Spinal Fusion

Purpose: There are few reports of postoperative long-term malignant risk or postoperative sequelae after surgery for choledochal cysts (CCs). This study aimed to analyze the clinical characteristics of patients with malignancy and the longterm results of operated CC. Methods: The patients who underwent surgical treatments for CC between 2003 and 2020 at Seoul National University Hospital were enrolled. Clinicopathologic factors and pre-/postoperative computed tomography or magnetic resonance imaging were reviewed. Results: Of the 153 patients, Todani classification Ic (36.6%), C-P type (43.8%) anomalous pancreaticobiliary duct union were the most common type respectively. Fourteen patients (9.2%) had biliary tract cancer and a comparison of patients with and without malignancy showed that the diameter of cyst was significantly lower in malignant patients and malignancy was observed to be significantly higher in P-C type. The incidence of long-term complications was 9.8%, and the median time interval was 30 months. The 2 most common complications were cholangitis and stricture (60.0%). There was one case of new cancer near the intrapancreatic remnant bile duct. Conclusion Of the resected CCs, 9.2% had a combined malignancy on the biliary tracts. Long-term complications such as cholangitis, anastomotic stricture, and new cancers may occur. Therefore, continuous surveillance is required.