Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

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.

Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

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.

Transduced Tat-aldose Reductase Protects Hippocampal Neuronal Cells against Oxidative Stress-induced Damage

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.

Distribution of Rickettsia spp. in Ticks from Northwestern and Southwestern Provinces, Republic of Korea

This study was done to characterize distribution of Rickettsia spp. in ticks in the northwestern and southwestern provinces in the Republic of Korea. A total of 2,814 ticks were collected between May and September 2009. After pooling, 284 tick DNA samples were screened for a gene of Rickettsia-specific 17-kDa protein using nested PCR (nPCR), and produced 88 nPCR positive samples. Of these positives, 75% contained 190-kDa outer membrane protein gene (ompA), 50% 120-kDa outer membrane protein gene (ompB), and 64.7% gene D (sca4). The nPCR products of ompA, ompB, and sca4 genes revealed close relatedness to Rickettsia japonica, R. heilongjiangensis, and R. monacensis. Most Rickettsia species were detected in Haemaphysalis longicornis. This tick was found a dominant vector of rickettsiae in the study regions in the Republic of Korea.

Survey on the Status of Biosafety Awareness Among Domestic Biology Researchers

In this study, a survey was conducted to investigate the current status of biosafety awareness by each region, targeting domestic biology researchers. A total of 4 surveys were conducted from September 24 to October 2, 2013 in Kangwon province, Seoul Metropolitan area, Chungchong Province, and Gyeongsang Province, and 189 respondents participated in the survey. Of the survey respondents, 135 (71.4%) answered that “It is likely for an infection to happen in the laboratory” and 23 (12.2%) answered “highly likely”. However, as to the Risk Group and Biosafety Facility Level, only 24 (12.7%) and 25 (13.2%) of the respondents, respectively, responded “know them very well”. These results indicate that researchers are aware of the need for the concept of biosafety in laboratories, but they lack systematic education and publicity. Therefore, it will be necessary to develop a system that can systematically educate the regulations and compliance of biosafety.

Emerging Infectious Diseases Require Biosafety Awareness and Procedures

In 2015, there was a Middle East respiratory syndrome (MERS) outbreak in Korea. Interestingly, most of the cases were nosocomial infection and significant numbers of healthcare workers (HCWs) were infected. There were various causes, but this study focused on HCWs and their ability to self-protect from infectious materials. HCWs did not receive sufficient instruction or training on biosafety, including how to use personal protection equipment and risk assessment at the beginning of the outbreak. Previous experience from an outbreak of severe acute respiratory syndrome or Ebola showed that HCWs must self-protect from infection sources, but HCW infection occurred again with this MERS outbreak. Therefore, the concept of biosafety self-protection must be emphasized so that HCWs can protect themselves from diseases and avoid spreading them.

Identification of Leptospira species of Korean Isolates using Phylogenetic Analysis of Polymerase Chain Reaction-amplified 16S rDNA and LipL32 Genes

In this study, we selected only serologically identified 15 Leptosira interrogans isolates in the past and analyzed and identified them by using molecular method. The partial 16S rDNA and LipL32 genes were amplified from the bacteria by polymerase chain reaction (PCR) and sequenced. Sizes of the PCR products were 529 bp and 819 bp respectively and analysis of the nucleotide sequence of 16S rDNA and LipL32 genes showed that 14 out the 15 Leptospira showed 99.4~100% and 99.2~99.9% similarity respectively to those of L. interrogans lai and one isolate named HS-7 showed 100% and 100% similarity to L. interrogans canicola. The phylogenetic tree based on the 16S rDNA and LipL32 genes obtained the study revealed that 14 of the Leptospira composed a cluster distinct to that of L. interrogans lai and HS-7 composed to L. interrogans canicola.

Larval Chigger Mites Collected from Small Mammals in 3 Provinces, Korea

A total of 9,281 larval chigger mites were collected from small mammals captured at Hwaseong-gun, Gyeonggi-do (Province) (2,754 mites from 30 small mammals), Asan city, Chungcheongnam-do (3,358 mites from 48 mammals), and Jangseong-gun, Jeollanam-do (3,169 for 62 mammals) from April-November 2009 in the Republic of Korea (= Korea) and were identified to species. Leptotrombidium pallidum was the predominant species in Hwaseong (95.8%) and Asan (61.2%), while Leptotrombidium scutellare was the predominant species collected from Jangseong (80.1%). Overall, larval chigger mite indices decreased from April (27.3) to June (4.9), then increased in September (95.2) and to a high level in November (169.3). These data suggest that L. pallidum and L. scutellare are the primary vectors of scrub typhus throughout their range in Korea. While other species of larval chigger mites were also collected with some implications in the transmission of Orientia tsutsugamushi, they only accounted for 11.2% of all larval chigger mites collected from small mammals.

The Management of Laboratory Biological Safety in Korea

The Laboratories engaging with microorganisms have some potential risks, depending on handling of pathogens. The safety management system to extend recognition of biosafety and biosecurity needs to be established and practiced in order to prevent hazard possibility and secure safety of researchers who deal with pathogen. As the importance and regulation of global biosafety and biosecurity tended to be intensified, various laws and institutions for the security of biosafety were established when the Act on implementation of Living Modified Organisms, an implantation act of Cartagena was enforced in Korea in 2008. In particular, the system of permission report for Living Modified Organism (LMO), Highly Dangerous Pathogens (HDPs) and Biological Weapons Convention (BWC), in order to prevent intended or non-intended leakage and occurrence of biohazard derived from pathogen and infectious substance and safely use them. The bioterrorism can be controlled and autonomous management of biosafety by agencies that handle pathogens can be also secured by practicing the various laws and institutions.

A Survey on Laboratory Biosafety Status of Public Healthcare Centers in Korea

The purpose of this study was to explore the laboratory biosafety status of Public Health Centers (PHCs) in Korea during Oct.7~26, 2012. We surveyed the environment of biosafety management, especially for the recognition level for biosafety of workers in the organizations. The questionnaires given out to 98 workers who are working for PHCs are to research the recognition level of workers for the knowledge of biosafety, related laws and regulations. The level was the highest in the Research Institute of the Public Health & Environment (RIPHE) followed by quarantine station, and the health center was assessed as the last. It was turned out that the biosafety educational program in the RIPHE was implemented on a regular basis (65.2%) with irregular cases (21.7%), and some outsourcing chances (8.7%). However, quarantine stations and health centers didn't practice actively biosafety training programs compared to RIPHE. In addition, there was a majority of opinions that the most important thing to improve biosafety level of PHCs is to strengthen current poor training and education system. In conclusion, it is necessary to develop more improved training system for biosafety on exposure risks including injuries, personal protective equipment, and chemical hazards.

Affects of "Age at Diagnosis" on Coronary Artery Lesions in Patients With Incomplete Kawasaki Disease

BACKGROUND AND OBJECTIVES: Diagnosis of Kawasaki disease (KD) is based on 5 clinical features. Incomplete KD (IKD), which has fewer features, is more common in infants and older children, in whom the rate of coronary artery aneurysms is paradoxically higher. We conducted this study to evaluate risk factors associated with age-at-diagnosis on coronary arterial lesions (CAL) in patients with IKD. SUBJECTS AND METHODS: Retrospective data from 396 patients with KD in a single center were collected from January 2003 to July 2007. Patients were grouped according to their age at diagnosis; Group A ( or =5 years of age). RESULTS: Among a total of 396 patients with KD, 87 (22.0%) were in Group A, 246 (62.1%) in Group B, and 63 (15.9%) in Group C. In groups A and C, lag times for starting intravenous immunoglobulin (IVIG) were longer than in Group B. There were no differences in the incidence of IKD, late CAL, or rates of IVIG retreatment among the three groups. Among 174 patients with IKD, there were no age-related differences in late CAL incidence or IVIG retreatment. Compared with typical KD, duration of fever and lag times to start IVIG were longer, and the rate of IVIG retreatment was higher in IKD, but there was no difference in the risk of CAL between typical KD and IKD. CONCLUSION: In the management of KD, especially the incomplete type, age-associated factors appear not to be significant for predicting the development of CAL.

Detection and Identification of the Spotted Fever Group Rickettsial Agents from Haemaphysalis Ticks in Jeju Island, Korea

This study investigated the presence of nucleic acids of various Rickettsial agents in ticks collected in Jeju Island, Korea from June 2007 to August 2008, through the nested polymerase chain reaction (PCR) and sequencing analysis of partial citrate synthase (gltA), Rickettsial outer membrane protein B (ompB), and 17-kDa genes. Examination of the 1,584 ticks showed that the subspecies distribution of Haemaphysalis longicornis was 99.81% (n=1,581) and H. flava was 0.19% (n=3). A total 224 out of 250 pools from one to 15 ticks were found to be positive in ompB-PCR assay (minimal infection rate 141 ticks/1,000 tested). From the positive samples, 26 were analyzed by gltA- and 17-kDa-PCR assays. The nucleotide sequences of the ompB- and gltA-PCR products showed a high degree of similarity with those of the Rickettsia japonica (98.7~99.2% and 98.7~99.3%, n=25) and R. monacensis (99% and 99.7%, n=1). However, analysis of the nucleotide sequences of the 17-kDa-PCR amplicons showed that the sequences of the 25 PCR amplicons were more close to R. marmionii (99.4~100%) than R. japonica (98.6~99.1%). These findings suggest that various rickettsial diseases could be transmitted via the bite of tick vectors in Jeju Island, Korea.

The Effects of Intravenous Anesthetics on Human Cytomegalovirus Infection / 대한마취과학회지

BACKGROUND: Reactivation of human cytomegalovirus (HCMV) from latency is a frequent complication of organ transplantation, and the molecular mechanism by which this occurs is unknown. Previous studies have shown that allogenaic transplantation combined with immunosuppression may be required to achieve complete reactivation in vivo and many anesthetics have wide range immunomodulatory properties. HCMV infection of endothelial cells plays an important role in the establishment of latency and persistence, which appears critical for the maintenance of HCMV within the host. METHODS: We compared the effects of intravenous anaesthetics (propofol, thiopental, and ketamine) on the susceptability of endothelial cells to HCMV infection by indirect immunofluorescent assay at 48 hour postinfection and we also have investigated the time course of luciferase gene expression in human umbilical vein endothelial cell (HUVEC) infected with recombinant HCMV. RESULTS: Treatment with anesthetics after HCMV strain Towne inoculation did not increase HUVEC susceptibility to HCMV infection by indirect immunofluorescent assay. Treatment of HUVEC with propofol, thiopental, and ketamine after the recombinant virus inoculation had no significant effects on the level of the late genes expression. CONCLUSIONS: Intravenous anesthetics (propofol, thiopental, and ketamine) did not increase the susceptability of endothelial cells to HCMV infection at plasma concentrations. Further studies are required to evaluate higher anesthetic concentration which may increases the susceptability of HUVEC to HCMV infection without cell destruction.

Characterization and Distribution of Dendritic Cells and Tissue Macrophages in the Rat Ovary / 대한해부학회지

This study was undertaken to investigate the characterization and distribution patterns of MHC class II positive dendritic cells[DCs] and ED2 positive tissue macrophages throughout the estrous cycle and during pregnancy in the rat ovary. The immunohistochemical characterization of the cells was carried out using the monoclonal antibodies OX6 and ED2 in cryostat-cut sections. DCs were distributed in the theca cell layer of the growing and mature follicles,stroma and corpus luteum. Tissue macrophages were distributed in the theca externa of the growing and mature follicles, stroma and corpus luteum but they were smaller in number than DCs. None of DC and tissue macrophage was found in the ovum, granulosa layer and follicular cavity of the ovarian follicle. However, DCs and tissue macrophages were present in the granulosa layer and follicular cavity in the atretic follicles. Degenerating corpus luteum contained a vast number of OX6 positive cells. On the contrary, fewer tissue macrophages were founcl in the degenerating corpus luteum. More macrophages tended to be observed in the former follicular cavity and theca lutein cell layer than in the granulosa lutein cell layer of the corpus luteum. In stroma,DCs and tissue macrophages were more frequently found around the blood vessels than in the other region, however, DCs were relatively greater in number than tissue macrophages. There was no estrous cycle and pregnancy dependent variation in the numbers and distribution patterns of DCs and tissue macrophages. In conclusion, the rat ovary contains rich networks of MHC class II positive dendritic cells and ED2 positive tissue macrophages. These findings suggest the existence of a well-developed system of immunological surveillance in the rat ovary. The results of this study have potentially important implications for the understanding not only of the ovarian immune system and the pathogenesis of various ovarian diseases but also of various physiologic functions of the ovary.

Phenotypic Changes of Intermediate Filament Proteins of Skeletal Muscles following Sciatic Nerve Injury Expression of Desmin and Vimentin of Experimental Neurogenic Myopathy / 체질인류학회지

No abstract available.