The estimation of age is an important issue in forensic science, and the forensic community has attempted many times to establish methods for solving this issue. Aging leads to alterations in tissues and organs at the molecular level. These alterations at the molecular level may aid forensic scientists to estimate the age of a living person or a dead body. Initially, the focus was on the genetic components of aging, but recently, epigenetic mechanisms have emerged as the key contributors to the alterations in genome structure and function that accompany aging. In particular, DNA methylation is one of the best-understood mechanisms, and it has been suggested as a promising biomarker for age estimation in many studies. In this review, we summarize the recent studies on age-associated DNA methylation changes in different tissues and discuss its possible and practical applications in forensics.
Aging ; DNA ; DNA Methylation ; Epigenomics ; Forensic Sciences ; Genome ; Humans

Patients receiving hemodialysis are vulnerable to infectious diseases due to their impaired immunity and high risk of exposure to pathogens. To protect patients, staff, and visitors from potential infections, each hemodialysis unit should establish and follow standard infection control and prevention measures. Therefore, clinical practice guidelines were developed by a working group of nephrologists and infection control specialists to provide evidence-based guidance for dialysis physicians and nurses, with the aim of preventing infection transmission and controlling infection sources in hemodialysis facilities. The areas of infection control covered by these guidelines include standard precautions, isolation strategies, vascular access, water treatment, cleaning/disinfecting/sterilizing, and vaccination. This special report summarizes the key recommendations from the Korean clinical practice guidelines for preventing the transmission of infections in hemodialysis facilities.
Communicable Diseases ; Dialysis ; Disease Transmission, Infectious ; Humans ; Infection Control ; Renal Dialysis* ; Specialization ; Vaccination ; Water Purification

BACKGROUND: Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells. Recent studies have revealed that PRMT1 plays important roles in the development of various tissues. However, its role in pancreas development has not yet been elucidated. METHODS: Pancreatic progenitor cell-specific Prmt1 knock-out (Prmt1 PKO) mice were generated and characterized for their metabolic and histological phenotypes and their levels of Neurog3 gene expression and neurogenin 3 (NGN3) protein expression. Protein degradation assays were performed in mPAC cells. RESULTS: Prmt1 PKO mice showed growth retardation and a severely diabetic phenotype. The pancreatic size and β-cell mass were significantly reduced in Prmt1 PKO mice. Proliferation of progenitor cells during the secondary transition was decreased and endocrine cell differentiation was impaired. These defects in pancreas development could be attributed to the sustained expression of NGN3 in progenitor cells. Protein degradation assays in mPAC cells revealed that PRMT1 was required for the rapid degradation of NGN3. CONCLUSION: PRMT1 critically contributes to pancreas development by destabilizing the NGN3 protein.
Animals ; Diabetes Mellitus ; Endocrine Cells ; Gene Expression ; Islets of Langerhans ; Mice ; Pancreas ; Phenotype ; Protein Stability ; Protein-Arginine N-Methyltransferases ; Proteolysis ; Stem Cells

BACKGROUND/AIMS: Hepatitis A virus (HAV) is a self-limiting infectious disease, but 1% of subjects develop fulminant hepatitis. The prevalence of the anti-HAV immunoglobulin G (IgG) antibody in hemodialysis subjects in Korea remains unknown. The purpose of this study was to describe and compare the seropositive rate of anti-HAV antibody among hemodialysis subjects in two hospitals according to age group. METHODS: A total of 170 hemodialysis subjects were evaluated for the seropositive rate of the anti-HAV IgG antibody and its titer. RESULTS: Of the 170 maintenance hemodialysis subjects in two hospitals (Kangnam 92 vs. Chuncheon 78), 79 (46.5%) were male. The mean age was 53.2 years old, and 94.1% of the subjects were over 40 years old. The median vintage of hemodialysis was 29.0 months. Anti-HAV antibody was found in 163 subjects (95.9%), with no significant difference between the two areas (Kangnam 97.8% [n = 90] vs. Chuncheon 93.6% [n = 73]). Subjects younger than 40 years old showed a seropositive rate of 50%, while the seropositive rate increased with age for subjects aged 40 or older (p for trend < 0.001). Seropositive subjects from Kangnam showed a higher anti-HAV antibody titer than those from Chuncheon (median: Kangnam 14.2 vs. Chuncheon 11.7). Only age influenced seropositivity. The only factor that influenced the antibody level was the location of hospital (p < 0.001). CONCLUSIONS The seropositive rate of the anti-HAV antibody in hemodialysis subjects was 95%, which is similar to findings in the general population. Active immunization against hepatitis A is strongly recommended for hemodialysis subjects under 40 years of age after anti-HAV testing.

Idiopathic membranous nephropathy is a common cause of nephrotic syndrome, and has been reported as a cause of idiopathic primary glomerulonephropathy in up to 90% of patients. However, the treatment options remain controversial. We report two cases of idiopathic membranous nephropathy that were treated with rituximab. A 54-year-old man and a 64-year old man were admitted for rituximab therapy. They had previously been treated with combinations of immunosuppressive agents including cyclophosphamide, cyclosporine, mycophenolate, and steroids. However, the patients' heavy proteinuria was not resolved. Both patients received rituximab therapy, 2 weeks apart. After several months of follow-up and a second round of rituximab treatment for each patient, their proteinuria decreased and partial remission of disease was achieved in both patients.
Antibodies, Monoclonal, Murine-Derived ; Cyclophosphamide ; Cyclosporine ; Follow-Up Studies ; Glomerulonephritis, Membranous* ; Humans ; Immunosuppressive Agents ; Middle Aged ; Nephrotic Syndrome ; Proteinuria ; Steroids ; Rituximab

AMP-activated protein kinase (AMPK) is a metabolic sensor activated during metabolic stress and it regulates various enzymes and cellular processes to maintain metabolic homeostasis. We previously reported that activation of AMPK by glucose deprivation (GD) and leptin increases KATP currents by increasing the surface levels of KATP channel proteins in pancreatic beta-cells. Here, we show that the signaling mechanisms that mediate actin cytoskeleton remodeling are closely associated with AMPK-induced KATP channel trafficking. Using F-actin staining with Alexa 633-conjugated phalloidin, we observed that dense cortical actin filaments present in INS-1 cells cultured in 11 mM glucose were disrupted by GD or leptin treatment. These changes were blocked by inhibiting AMPK using compound C or siAMPK and mimicked by activating AMPK using AICAR, indicating that cytoskeletal remodeling induced by GD or leptin was mediated by AMPK signaling. AMPK activation led to the activation of Rac GTPase and the phosphorylation of myosin regulatory light chain (MRLC). AMPK-dependent actin remodeling induced by GD or leptin was abolished by the inhibition of Rac with a Rac inhibitor (NSC23766), siRac1 or siRac2, and by inhibition of myosin II with a myosin ATPase inhibitor (blebbistatin). Immunocytochemistry, surface biotinylation and electrophysiological analyses of KATP channel activity and membrane potentials revealed that AMPK-dependent KATP channel trafficking to the plasma membrane was also inhibited by NSC23766 or blebbistatin. Taken together, these results indicate that AMPK/Rac-dependent cytoskeletal remodeling associated with myosin II motor function promotes the translocation of KATP channels to the plasma membrane in pancreatic beta-cells.
AMP-Activated Protein Kinases/metabolism ; Actins/*metabolism ; Animals ; Cell Line ; Glucose/metabolism ; Insulin-Secreting Cells/*metabolism ; KATP Channels/*metabolism ; Leptin/metabolism ; Myosin Type II/*metabolism ; Phosphorylation ; Rats ; *Signal Transduction ; rac GTP-Binding Proteins/*metabolism

PURPOSE: Urinary angiotensinogen (AGT) has been reported as an important marker reflecting the activity of intrarenal renin-angiotensin system (RAS) in chronic glomerulonephritis patients. We investigated urinary AGT excretion and intrarenal AGT expression in patients with minimal change disease (MCD). METHODS: In 20 patients with biopsy-proven MCD, urinary and plasma AGT was measured using a sandwich ELISA and intrarenal AGT expression was measured with immunohistochemistry. Urine samples from normal healthy volunteers and patients with biopsy-proven thin basement membrane disease (TBM) were used as control groups. RESULTS: MCD patients showed a wide range of natural logarithm of the urinary AGT/creatinine [ln (urinary AGT/Cr)] and the ln (urinary AGT/Cr) was higher in MCD patients compared with normal controls and TBM controls (normal control vs. TBM vs. MCD, 1.2+/-0.25 vs. 0.9+/-0.34 vs. 3.2+/-0.40). Intrarenal AGT expression was diverse in MCD patients (intrarenal AGT, arbitrary unit, 27.39-78.52 in TBM, 0.00-145.80 in MCD). Ln (urinary AGT/Cr) did not show a direct correlation with intrarenal AGT expression, plasma AGT, or urinary protein/creatinine ratio. CONCLUSION: Urinary AGT excretion and intrarenal AGT expression are enhanced in some MCD patients, suggesting that intrarenal RAS is activated in these patients.
Angiotensinogen ; Basement Membrane ; Corneal Dystrophies, Hereditary ; Enzyme-Linked Immunosorbent Assay ; Glomerulonephritis ; Humans ; Immunohistochemistry ; Nephrosis, Lipoid ; Plasma ; Proteinuria ; Renin-Angiotensin System

Patients with end-stage kidney disease face increased risk of cardiovascular events, and left ventricular diastolic dysfunction (LVDD) contributes to the high occurrence of cardiovascular mortality (CM). Although a high serum aldosterone (sALD) level is involved in the development of cardiovascular complications in the general population, this association is unclear in patients undergoing hemodialysis. We aimed to determine the impact of sALD on LVDD and CM among hemodialysis patients (HDPs). Methods: We performed a prospective cohort study of maintenance HDPs without cardiovascular disease. The patients were divided into two groups according to the median level of sALD. All patients underwent baseline echocardiography to evaluate diastolic dysfunction (E/e’ ratio > 15). The LVDD and CM rates were compared between the high and low aldosterone groups. Results: We enrolled a total of 60 adult patients (mean age, 57.9 ± 12.1 years; males, 30.0%). The low aldosterone group had an increased left ventricular diastolic dimension compared with the high aldosterone group (52.2 ± 8.4 mm vs. 50.3 ± 5.2 mm, respectively; p = 0.03). Low log-aldosterone (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.19–0.86) and large left atrial dimension (OR, 1.31; 95% CI, 1.11–1.54) were independent risk factors for LVDD at baseline. In addition, Cox regression analysis demonstrated that low sALD was an independent predictor of CM in HDPs (hazard ratio, 0.46; 95% CI, 0.25–0.85; p = 0.01) during follow-up. Conclusion: Low sALD was not only associated with LVDD but was also an independent predictor of CM among HDPs regardless of their interdialytic weight gain.

Methods: This is a post hoc analysis of a prospective, controlled, randomized, unblinded study with 78 Korean hemodialysis patients receiving intravenous (n = 40) or subcutaneous (n = 38) erythropoietin therapy. We evaluated hemoglobin variability by calculating the frequency of hemoglobin measurements outside the target range during all visits. The high-frequency group was defined by those with hemoglobin variability over the median value (25%) while the low-frequency group was defined by those with hemoglobin variability of <25%. Results: In this analysis, 37 patients (51.1%) were men, and the mean age was 50.6 ± 12.5 years. Twenty-five patients (35.2%) had diabetes mellitus. The frequency of the value being outside the target hemoglobin range was higher in the subcutaneous group compared to the intravenous group (0.36 ± 0.19 vs. 0.27 ± 0.12/visit, p = 0.03). The low-frequency group required significantly lower erythropoietin doses compared to the high-frequency group. In the adjusted Cox analysis, the parameter high-frequency group was a significant independent risk factor for cardiovascular events (hazard ratio, 3.53; 95% confidence interval, 1.15–10.83; p = 0.03). Conclusion The risk of missing the target hemoglobin range increased with subcutaneous administration compared with intravenous erythropoietin administration in hemodialysis patients. An increased frequency of the value being outside the target hemoglobin range was also associated with an increased risk of cardiovascular events.

Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (COVID-19), there are lack of effective and proven treatments for end-stage renal disease (ESRD). The present study aims to evaluate the effectiveness of regdanvimab on mortality in COVID-19–infected patients on hemodialysis (HD). Methods: We conducted an observational retrospective study in 230 COVID-19–infected patients on HD, of whom 77 (33.5%) were administered regdanvimab alone or in combination with dexamethasone or remdesivir during hospitalization (regdanvimab group) and 153 patients (66.5%) were not (no regdanvimab group). The primary outcome was in-hospital mortality. We compared mortality rates according to the use of regdanvimab and investigated the factors associated with mortality. Results: Fifty-nine deaths occurred during hospitalization, 49 in the no regdanvimab group (32.0%) and 10 in the regdanvimab group (13.0%), and the mortality rate was significantly higher in the no regdanvimab group than that in the regdanvimab group (p = 0.001). Multivariate Cox regression analysis showed that malignancy (p = 0.001), SPO2 of <95% at admission (p = 0.003), and administration of antibiotics and regdanvimab (p = 0.007 and p = 0.002, respectively) were significantly associated factors with mortality. Conclusion: Regdanvimab administration is beneficial in improving prognosis in hospitalized COVID-19 patients on HD. Considering the vulnerability to infection and high mortality of ESRD patients, regdanvimab may be considered as a therapeutic option in COVID-19 patients on HD.