Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Purpose: The aim of this study was to analyze the age group characteristics and factors associated with the severe trauma in children who visited a regional trauma center. Methods: We reviewed children aged 18 years or younger who visited a regional trauma center, equivalent to level 1 trauma centers in the United States, in Incheon, Korea from July 2014 through December 2019. They were classified by the age groups: preschoolers (0-6 years), schoolers (7-12 years), and adolescents (13-18 years). Across the 3 age groups, event profiles, severity, and outcomes of injury were compared. Multivariable logistic regressions were used to identify factors associated with the severe trauma, defined as the Injury Severity Score of 16 or higher. Results: Among the total of 367 children, 74 (20.2%) were preschoolers, 73 (19.9%) were schoolers, and 220 (59.9%) were adolescents. The most common injury mechanisms in the preschoolers, schoolers, and adolescents were fall (40.5%), pedestrian collision (32.9%), and motorcycle accident (38.6%), respectively. The adolescents had the highest median Injury Severity Score (13 [6-23]; P < 0.001). In the multivariable analyses, the Glasgow Coma Scale of 3-8 (odds ratio [OR], 14.60; 95% confidence interval, 5.40-39.42) had the highest OR for severe trauma, followed by injury in the abdomen or pelvic contents (OR, 11.61; 95% confidence interval, 4.66-28.89). Conclusion In pediatric trauma, the mechanism and severity of injury may differ according to age groups, with the severe trauma associated with injuries to the head and torso. It is advisable to have age group-specific approaches and strategies for injury prevention.

Purpose: The aim of this study was to analyze the age group characteristics and factors associated with the severe trauma in children who visited a regional trauma center. Methods: We reviewed children aged 18 years or younger who visited a regional trauma center, equivalent to level 1 trauma centers in the United States, in Incheon, Korea from July 2014 through December 2019. They were classified by the age groups: preschoolers (0-6 years), schoolers (7-12 years), and adolescents (13-18 years). Across the 3 age groups, event profiles, severity, and outcomes of injury were compared. Multivariable logistic regressions were used to identify factors associated with the severe trauma, defined as the Injury Severity Score of 16 or higher. Results: Among the total of 367 children, 74 (20.2%) were preschoolers, 73 (19.9%) were schoolers, and 220 (59.9%) were adolescents. The most common injury mechanisms in the preschoolers, schoolers, and adolescents were fall (40.5%), pedestrian collision (32.9%), and motorcycle accident (38.6%), respectively. The adolescents had the highest median Injury Severity Score (13 [6-23]; P < 0.001). In the multivariable analyses, the Glasgow Coma Scale of 3-8 (odds ratio [OR], 14.60; 95% confidence interval, 5.40-39.42) had the highest OR for severe trauma, followed by injury in the abdomen or pelvic contents (OR, 11.61; 95% confidence interval, 4.66-28.89). Conclusion In pediatric trauma, the mechanism and severity of injury may differ according to age groups, with the severe trauma associated with injuries to the head and torso. It is advisable to have age group-specific approaches and strategies for injury prevention.

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.
Aldehyde Reductase ; Aldehydes ; Blood-Brain Barrier ; Brain ; CA1 Region, Hippocampal ; Caspase 3 ; Cell Death ; Cell Survival ; Humans ; In Vitro Techniques ; Ischemia ; Models, Animal ; Neurons ; Oxidative Stress ; Oxidoreductases ; Protein Kinases

Bioresorbable vascular scaffold (BRS) is an innovative device that provides structural support and drug release to prevent early recoil or restenosis, and then degrades into nontoxic compounds to avoid late complications related with metallic drug-eluting stents (DESs). BRS has several putative advantages. However, recent randomized trials and registry studies raised clinical concerns about the safety and efficacy of first generation BRS. In addition, the general guidance for the optimal practice with BRS has not been suggested due to limited long-term clinical data in Korea. To address the safety and efficacy of BRS, we reviewed the clinical evidence of BRS implantation, and suggested the appropriate criteria for patient and lesion selection, scaffold implantation technique, and management.
Coronary Disease ; Drug Liberation ; Drug-Eluting Stents ; Humans ; Korea ; Stents ; Thrombosis

Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF. Post treatment with PMOC sequentially ameliorated hepatic inflammation, apoptosis of hepatocytes, severe liver injury and shock-mediated death in ALF-induced mice. As a mechanism, PMOC inhibited the catalytic activity of TGF-β-activated kinase 1 (TAK1) in a competitive manner with respect to ATP, displaced fluorescent ATP probe from the complex with TAK1, and docked at the ATP-binding active site on the crystal structure of TAK1. Moreover, PMOC inhibited TAK1 auto-phosphorylation, which is an axis in the activating pathways of nuclear factor-κB (NF-κB) or activating protein 1 (AP1), in the liver with ALF in vivo or in primary liver cells stimulated with TLR agonists in vitro. PMOC consequently suppressed TAK1-inducible NF-κB or AP1 activity in the inflammatory injury, an early pathogenesis leading to ALF. The results suggested that PMOC could contribute to the treatment of TLR/MyD88-associated ALF with the ATP-binding site of TAK1 as a potential therapeutic target.
Adenosine Triphosphate ; Animals ; Apoptosis ; Catalytic Domain ; Chalcone ; Death, Sudden ; Escherichia coli ; Hepatocytes ; In Vitro Techniques ; Inflammation ; Liver ; Liver Failure, Acute* ; Mice ; Myeloid Differentiation Factor 88 ; Phosphotransferases ; Plants, Medicinal ; Toll-Like Receptors

Data on the clinical outcomes in deferred coronary lesions according to functional severity have been limited. This study evaluated the clinical outcomes of deferred lesions according to fractional flow reserve (FFR) grade using Korean FFR registry data. Among 1,294 patients and 1,628 lesions in Korean FFR registry, 665 patients with 781 deferred lesions were included in this study. All participants were consecutively categorized into 4 groups according to FFR; group 1: ≥ 0.96 (n = 56), group 2: 0.86–0.95 (n = 330), group 3: 0.81–0.85 (n = 170), and group 4: ≤ 0.80 (n = 99). Primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, and target vessel revascularization. The median follow-up period was 2.1 years. During follow-up, the incidence of MACE in groups 1–4 was 1.8%, 7.6%, 8.8%, and 13.1%, respectively. Compared to group 1, the cumulative rate by Kaplan-Meier analysis of MACE was not different for groups 2 and 3. However, group 4 had higher cumulative rate of MACE compared to group 1 (log-rank P = 0.013). In the multivariate Cox hazard models, only FFR (hazard ratio [HR], 0.95; P = 0.005) was independently associated with MACE among all participants. In contrast, previous history of percutaneous coronary intervention (HR, 2.37; P = 0.023) and diagnosis of acute coronary syndrome (ACS) (HR, 2.35; P = 0.015), but not FFR, were independent predictors for MACE in subjects with non-ischemic (FFR ≥ 0.81) deferred coronary lesions. Compared to subjects with ischemic deferred lesions, clinical outcomes in subjects with non-ischemic deferred lesions according to functional severity are favorable. However, longer-term follow-up may be necessary.
Acute Coronary Syndrome ; Coronary Artery Disease ; Diagnosis ; Follow-Up Studies ; Humans ; Incidence ; Kaplan-Meier Estimate ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Prognosis ; Proportional Hazards Models

The incidence rate of cervical cancer in Korea is still higher than in other developed countries, notwithstanding the national mass-screening program. Furthermore, a new method has been introduced in cervical cancer screening. Therefore, the committee for cervical cancer screening in Korea updated the recommendation statement established in 2002. The new version of the guideline was developed by the committee using evidence-based methods. The committee reviewed the evidence for the benefits and harms of the Papanicolaou test, liquid-based cytology, and human papillomavirus (HPV) testing, and reached conclusions after deliberation. The committee recommends screening for cervical cancer with cytology (Papanicolaou test or liquid-based cytology) every three years in women older than 20 years of age (recommendation A). The cervical cytology combined with HPV test is optionally recommended after taking into consideration individual risk or preference (recommendation C). The current evidence for primary HPV screening is insufficient to assess the benefits and harms of cervical cancer screening (recommendation I). Cervical cancer screening can be terminated at the age of 74 years if more than three consecutive negative cytology reports have been confirmed within 10 years (recommendation D).
Adult ; Age Factors ; Aged ; Early Detection of Cancer/adverse effects/*methods/standards ; Evidence-Based Medicine ; False Positive Reactions ; Female ; Humans ; Hysterectomy ; Middle Aged ; Papillomavirus Infections/diagnosis ; Papillomavirus Vaccines ; Patient Selection ; Pregnancy ; Pregnancy Complications, Neoplastic/diagnosis ; Republic of Korea ; Review Literature as Topic ; Uterine Cervical Neoplasms/*diagnosis ; Vaginal Smears/adverse effects/methods/standards ; Young Adult

The incidence rate of cervical cancer in Korea is still higher than in other developed countries, notwithstanding the national mass screening program. Furthermore, a new method has been introduced in cervical cancer screening. Therefore, the committee for cervical cancer screening in Korea updated the recommendation statement established in 2002. The new version of the guideline was developed by the committee using evidence-based methods. The committee reviewed the evidence for the benefits and harms of the Papanicolaou test, liquid-based cytology, and human papilloma virus (HPV) testing, and reached conclusions after deliberation. The committee recommends screening for cervical cancer with cytology (papanicolaou test or liquid-based cytology) every three years in women older than 20 years of age (recommendation A). The combination test (cytology with HPV test) is optionally recommended after taking into consideration individual risk or preference (recommendation C). The current evidence for primary HPV screening is insufficient to assess the benefits and harms of cervical cancer screening (recommendation I). Cervical cancer screening can be terminated at the age of 74 years if more than three consecutive negative cytology reports have been confirmed within ten years (recommendation D).
Developed Countries ; Female ; Humans ; Incidence ; Korea ; Mass Screening* ; Papanicolaou Test ; Papilloma ; Uterine Cervical Neoplasms*