No abstract available.
Biological Science Disciplines*

PURPOSE: Acute kidney injury (AKI) is a common, serious complication in rhabdomyolysis patients. Early recognition and adequate therapy in rhabdomyolysis-related AKI are essential to reducing mortality. However, existing biomarkers, such as plasma creatinine, have several limitations for early detection of AKI. Novel parameters have recently been studied for greater reliability in prediction and staging of AKI in critically ill patients in the emergency department. The aim of this study is to evaluate the role of certain parameters for early prediction and staging of AKI in adults with acute non-traumatic rhabdomyolysis. METHODS: Eighty eight patients with adult non-traumatic rhabdomyolysis, who were admitted to the emergency intensive care unit (ICU) from Dec 2013 to Nov 2014, were enrolled in this observational cohort study. AKI was defined according to the Acute Kidney Injury Network (AKIN) criteria. Diagnostic characteristics of initial laboratory parameters were analyzed using the area under the receiver operating characteristic (ROC) curve. RESULTS: Of the 88 patients, 60 patients (68.2%) developed AKI during the ICU stay. The ROC curve for plasma neutrophil gelatinase-associated lipocalin (NGAL) showed the highest sensitivity (81.7%) and specificity (78.6%) among initial parameters. In pairwise comparison, the areas under the curve (AUCs) for plasma NGAL and serum creatinine were 0.868 (95% confidence interval [CI]: 0.779-0.931) and 0.765 (95% CI: 0.662-0.849), respectively. A statistically significant difference was observed in both (p=0.047). Plasma NGAL levels increased significantly as the stage of AKI progressed, using AKIN criteria (p<0.001). CONCLUSION: Plasma NGAL can be a reliable parameter for early prediction and approximate staging of AKI in adult non-traumatic rhabdomyolysis in the emergency department.
Acute Kidney Injury* ; Adult ; Biomarkers ; Cohort Studies ; Creatinine ; Critical Illness ; Diagnosis ; Emergencies* ; Emergency Service, Hospital* ; Humans ; Intensive Care Units ; Lipocalins ; Mortality ; Neutrophils ; Plasma ; Rhabdomyolysis* ; ROC Curve ; Sensitivity and Specificity

A century ago, more exactly 102 years ago, there was a devastating pandemic of influenza in 1918 and thereafter, periodic recurrences of pandemic events have been reported in the human population. Unfortunately, whenever it happened, the outcome was concomitant with over millions of death tolls due to considerably higher case fatality rates, compared to other infectious diseases at that time. In this regard, pandemics, which continued at irregular time intervals, give a great significance to global public health responses. However, it is far from feasibility to predict when a next pandemic will begin and how much disease burden will be despite our efforts to utilize all kinds of available scientific information and knowledge. The one clear thing is that approximately 70% of the causative agents of emerging and/or re-emerging diseases including COVID-19 (coronavirus disease 2019), which has been started from Wuhan province, China in December 2019 and has resulted in more than 4 million human cases within a few months, are viruses. Therefore, it is very important to secure fast and accurate identification methods of a causative pathogen in order to provide scientific clues and to prepare in advance for the abrupt occurrence of unknown viral diseases in a timely manner. In this review, the current status and future perspectives of the molecular technology for identification of viral pathogens such as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) with regard to rapid public health responses in the early stage of infectious diseases including COVID-19, will be discussed.

The recent mumps epidemic in South Korea has generated a large amount of public concern. This study has attempted to analyze molecular epidemiological changes of mumps virus circulating in Gwangju metropolitan area, South Korea. 953 throat swab samples were collected from patients with parotitis from May 2013 to July 2014. The majority (71.5%) of these cases have occurred in middle or high school students aged from 15 to 19 years. All samples were tested using a reverse transcription polymerase chain reaction (RT-PCR) that targets the short hydrophobic (SH) gene of the virus. Mumps virus SH gene was detected in 39.2% (374/953) of samples. And 82 RT-PCR products were randomly selected for nucleotide sequencing analysis. All of these sequences were determined as genotype I by phylogenetic analysis and showed the highest nucleic acid similarity (99%) with Dg1062/Korea/98 (GenBank accession no. AY309060). These results suggested that appearance of new genotype or genetic variation at the nucleotide level could be ruled out to evaluate main cause of recent mumps outbreak in Gwangju metropolitan area.
Genetic Variation ; Genotype ; Gwangju ; Humans ; Korea ; Molecular Epidemiology* ; Mumps ; Mumps virus* ; Parotitis ; Pharynx ; Polymerase Chain Reaction ; Reverse Transcription

Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.

Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.

We attempted to detect and identify virus types quickly by improving an RT-PCR-based dot-blot hybridization test for echoviruses, important human pathogens mainly causing aseptic meningitis. This test was applied to reference viruses of seven echovirus serotypes prevalent in Korea (E6, 7, 9, 11, 13, 25, and 30) and seventy isolates of echovirus isolated in Korea between 2002 and 2004. The primers for target DNA and hybridization probes (25mer, 50mer, and 70mer) were designed within the VP1 region of the echovirus. In RT-PCR, a nonradioactive digoxigenin-DNA labeling mix was added instead of dNTP to initiate PCR. The PCR product was then hybridized against 25mer, 50mer, and 70mer probe DNA spotted on nylon membranes and the reaction was observed. To investigate the optimal conditions for hybridization, various concentrations of target DNA (0.1, 1, 10, and 100 ng/micron l), size of probe DNA (25mer, 50mer, and 70mer), concentrations of probe DNA (10~50 pM), and reaction time were included. In the test zone, the optimal condition in terms of time and cost was a reaction time of 1 h with 10 ng/micron l target DNA concentration and 10 pM of a 50mer probe. We found 100% diagnosis of the serotypes for seven reference echoviruses and 90% (63/70) sensitivity for clinical isolates. Also, tests with this probe for reactivity with seven reference echoviruses by using DNA chips showed that diagnostic identification was possible without other serotype cross-reactivity. Therefore, efficiency analysis of probe and target DNA on clinical specimens by using dot-blot analysis indicated that this system can be applied to the prestages of the DNA chip and that the dot blot analysis itself can be used in applications to develop a tool for diagnosing specific viral serotypes.
Diagnosis ; DNA ; Enterovirus B, Human* ; Humans ; Korea ; Membranes ; Meningitis, Aseptic ; Nylons ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Reaction Time

The dynamics of the actin cytoskeleton plays a pivotal role in the process of cell division, the transportation of organelles, vesicle trafficking and cell movement. Human immunodeficiency virus type 1 (HIV-1) hijacks the actin dynamics network during the viral entry and migration of the pre-integration complex (PIC) into the nucleus. Actin dynamics linked to HIV-1 has emerged as a potent therapeutic target against HIV infection. Although some inhibitors have been intensely analyzed with regard to HIV-1 infection, their effects are sometimes disputed and the exact mechanisms for actin dynamics in HIV infection have not been well elucidated. In this study, the small molecules regulating HIV-1 infection from diverse inhibitors of the actin dynamic network were screened. Two compounds, including Chaetoglobosin A and CK-548, were observed to specifically bar the viral infection, while the cytochalasin family, 187-1, N-WASP inhibitor, Rho GTPase family inhibitors (EHop-016, CID44216842, and ML-141) and LIMK inhibitor (LIM domain kinase inhibitor) increased the viral infection without cytotoxicity within a range of ~ µM. However, previously known inhibitory compounds of HIV-1 infection, such as Latrunculin A, Jasplakinolide, Wiskostatin and Swinholide A, exhibited either an inhibitory effect on HIV-1 infection combined with severe cytotoxicity or showed no effects. Our data indicate that Chaetoglobosin A and CK-548 have considerable potential for development as new therapeutic drugs for the treatment of HIV infection. In addition, the newly identified roles of Cytochalasins and some inhibitors of Rho GTPase and LIMK may provide fundamental knowledge for understanding the complicated actin dynamic pathway when infected by HIV-1. Remarkably, the newly defined action modes of the inhibitors may be helpful in developing potent anti-HIV drugs that target the actin network, which are required for HIV infection.
Actin Cytoskeleton ; Actins ; Anti-HIV Agents ; Cell Division ; Cell Movement ; Cytochalasins ; GTP Phosphohydrolases ; HIV Infections ; HIV-1 ; Humans ; Organelles ; Phosphotransferases ; Transportation

The most effective way to control newly emerging infectious disease, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, is to strengthen preventative or therapeutic public health strategies before the infection spreads worldwide. However, global health systems remain at the early stages in anticipating effective therapeutics or vaccines to combat the SARS-CoV-2 pandemic. While maintaining social distance is the most crucial metric to avoid spreading the virus, symptomatic therapy given to patients on the clinical manifestations helps save lives. The molecular properties of SARS-CoV-2 infection have been quickly elucidated, paving the way to therapeutics, vaccine development, and other medical interventions. Despite this progress, the detailed biomolecular mechanism of SARS-CoV-2 infection remains elusive. Given virus invasion of cells is a determining factor for virulence, understanding the viral entry process can be a mainstay in controlling newly emerged viruses. Since viral entry is mediated by selective cellular proteases or proteins associated with receptors, identification and functional analysis of these proteins could provide a way to disrupt virus propagation. This review comprehensively discusses cellular machinery necessary for SARS-CoV-2 infection. Understanding multifactorial traits of the virus entry will provide a substantial guide to facilitate antiviral drug development.

The most effective way to control newly emerging infectious disease, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, is to strengthen preventative or therapeutic public health strategies before the infection spreads worldwide. However, global health systems remain at the early stages in anticipating effective therapeutics or vaccines to combat the SARS-CoV-2 pandemic. While maintaining social distance is the most crucial metric to avoid spreading the virus, symptomatic therapy given to patients on the clinical manifestations helps save lives. The molecular properties of SARS-CoV-2 infection have been quickly elucidated, paving the way to therapeutics, vaccine development, and other medical interventions. Despite this progress, the detailed biomolecular mechanism of SARS-CoV-2 infection remains elusive. Given virus invasion of cells is a determining factor for virulence, understanding the viral entry process can be a mainstay in controlling newly emerged viruses. Since viral entry is mediated by selective cellular proteases or proteins associated with receptors, identification and functional analysis of these proteins could provide a way to disrupt virus propagation. This review comprehensively discusses cellular machinery necessary for SARS-CoV-2 infection. Understanding multifactorial traits of the virus entry will provide a substantial guide to facilitate antiviral drug development.