Purpose: Acetaminophen (APAP) is a widely available drug responsible for a large part of drug-induced hepatotoxicity in developed countries. Although acetaminophen overdose cases in Korea are being continuously reported, there are no reports related to the level of this drug in the patient’s blood or of laboratory analysis at emergency departments (ED). This study sought to analyze the acetaminophen overdose cases at a toxicological laboratory and to survey APAP analysis services offered at select EDs. Methods: We analyzed the demographic and analytic data at a toxicological laboratory run by the National Emergency Medical Center (NMC) in 2019-2020. We surveyed the APAP laboratory service in the 38 regional emergency medical centers (EMCs) and 68 local EMCs near the toxicological laboratory. Results: We studied 175 acute poisoning cases (112 women) with positive blood APAP results (mean age 47.0±24.1 years).Suicide attempts comprised 40.0% of the cases and 30.3% APAP overdose events. In the univariate analysis, we observed that patients were significantly younger, with fewer underlying medical diseases. There were a higher number of APAP overdose events, more favorable initial mental status, more toxic quantity intake in the above treatment line group (p<0.05), In multivariate analysis, the toxic amount intake was significantly more frequent in the above treatment line group (p<0.01). Hospital APAP analysis services were available in six EMCs (3/38 regional and 3/68 local). The hospital blood APAP level reporting intervals were shorter than outside-hospital laboratory services (p<0.01, regional 7.0±3.0 vs. 40.6±27.5, local 5.3±3.1 vs. 57.9±45.1 hours).The NMC toxicological laboratory reporting interval was shorter than the other outside-hospital laboratories (p<0.01, regional 5.7± 0.6 vs. 50.2±22.7 local 7.5±3.0 vs. 70.5±41.5 hours). Conclusion Over the treatment line group, toxic amount intake was significantly more frequent. Only six of 106 EMCs have their own APAP analysis service in their hospitals.

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.
Alzheimer Disease ; Brain ; Brain Injury, Chronic* ; Cell Line ; Craniocerebral Trauma ; Gene Expression Profiling* ; Humans ; Models, Animal ; Neurodegenerative Diseases ; Phosphoprotein Phosphatases ; Phosphotransferases ; Sequence Analysis, RNA ; Tauopathies* ; Transcriptome*

Tyrosol, a phenylethanoid and a derivative of phenethyl alcohol, possesses various biological properties, such as anti-oxidative and cardioprotective activity. Olive oil is the principal source of tyrosol in the human diet. However, so far the anti-cancer activity of tyrosol has not yet been well defined. This study therefore undertakes to examine the cytotoxic activity and the mechanism of cell death exhibited by tyrosol in KB human oral cancer cells. Treatment of KB cells with tyrosol induced the cell growth inhibition in a concentration- and a time-dependent manner. Furthermore, the treatment of tyrosol induced nuclear condensation and fragmentation of KB cells. Tyrosol also promoted proteolytic cleavage of procaspase-3, -7, -8 and -9, increasing the amounts of cleaved caspase-3, -7, -8 and -9. In addition, tyrosol increased the levels of cleaved PARP in KB cells. These results suggest that tyrosol induces the suppression of cell growth and cell apoptosis in KB human oral cancer cells, and is therefore a potential candidate for anti-cancer drug discovery.
Apoptosis ; Caspase 3 ; Cell Death ; Diet ; Drug Discovery ; Humans* ; KB Cells ; Mouth Neoplasms* ; Olive Oil ; Phenylethyl Alcohol

β-carotene is present in carrots, pumpkins, and sweet potatoes. It suppresses many types of cancers by regulating cellular proliferation and apoptosis through a variety of mechanisms. However, the effects of β -carotene on oral cancer cells have not been clearly established. The main goal of this study was to investigate the effects of β-carotene on cell growth and apoptosis in oral cancer cells. Our results demonstrate that treatment with β-carotene induced inhibition of cell growth, and that the effect was dependent on β-carotene treatment time and concentration in KB cells. Furthermore, treatment with β-carotene induced nuclear condensation and fragmentation in KB cells. β-carotene promoted proteolytic cleavage of procaspase-3, -7, -8 and -9 with associated increases in the concentration of cleaved caspase-3, -7, -8 and -9. In addition, the level of cleaved PARP was increased by β-carotene treatment in KB cells. These results suggest that β-carotene can suppress cell growth and induce apoptosis in KB human oral cancer cells, and that it may have potential usefulness in anti-cancer drug discovery efforts.
Apoptosis ; Caspase 3 ; Cell Death ; Cell Proliferation ; Cucurbita ; Daucus carota ; Drug Discovery ; Humans* ; Ipomoea batatas ; KB Cells ; Mouth Neoplasms*

Curcumin (diferuloylmethane), a constituent of turmeric powder derived from the rhizome of Curcuma longa, has been shown to inhibit the growth of various types of cancer cells by regulating cell proliferation and apoptosis. However, a need exists to design more effective analogs because of curcumin's poor intestinal absorption. EF-24 (diphenyl difluoroketone), the monoketone analog of curcumin, has shown good efficacy in anticancer screens. However, the effects of curcumin and EF-24 on salivary gland epidermoid carcinoma cells are not clearly established. The main goal of this study was to investigate the effects of curcumin and EF-24 on cell growth and induction of apoptosis in human salivary gland epidermoid carcinoma cells. Our studies showed that curcumin and EF-24 inhibited the growth of HTB-41 cells in a dose- and time-dependent manner, and the potency of EF-24 was > 34-fold that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in HTB-41 cells, whereas the control HTB-41 cell nuclei retained their normal regular and oval shape. Curcumin and EF-24 promoted proteolytic cleavages of procaspase-3/-7/-9, resulting in an increase in the amount of cleaved caspase-3/-7/-9 in the HTB-41 cells. Caspase-3 and -7 activities were detected in viable HTB-41 cells treated with curcumin or EF-24. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptosis in HTB-41 human salivary gland epidermoid carcinoma cells, and that they may have potential properties as an anti-cancer drug therapy.
Apoptosis ; Carcinoma, Squamous Cell* ; Caspase 3 ; Cell Death ; Cell Nucleus ; Cell Proliferation ; Curcuma ; Curcumin* ; Drug Therapy ; Humans ; Intestinal Absorption ; Rhizome ; Salivary Glands*

Sambucus sieboldiana (SS) is a member of the family Caprifoliaceae and has been recommended as a functional material because of its several bioactivities. Although numerous literatures are available on the pharmacological and biological activities, the biological activity of SS in bone regeneration process has not yet been well-defined. Therefore, in this study, the effect of SS was investigated in the proliferation and differentiation of MC3T3-E1 osteoblastic cell line. The treatment of SS did not significantly affect the cell proliferation in MC3T3-E1 cells. SS significantly accelerated the mineralization and significantly increased the expression of alkaline phosphatase (ALP) and osteocalcin (OC) mRNAs, compared to the control, in the differentiation of MC3T3-E1 cells. SS significantly accelerated the decrease of osteonectin (ON) mRNA expression as compared with the control in a time-dependent manner in the differentiation of MC3T3-E1 cells. These results suggest that the SS facilitate the osteoblast differentiation and mineralization in MC3T3-E1 osteoblastic cells. Therefore, there may be potential properties for development and clinical application of bone regeneration materials.
Alkaline Phosphatase ; Bone Regeneration ; Caprifoliaceae ; Cell Line ; Cell Proliferation ; Extracellular Matrix* ; Humans ; Osteoblasts* ; Osteocalcin ; Osteogenesis ; Osteonectin ; RNA, Messenger ; Sambucus*

Human personal genome sequencing can be done with high efficiency by aligning a huge number of short reads derived from various next generation sequencing (NGS) technologies to the reference genome sequence. One of the major obstacles is the incompleteness of human reference genome. We tried to analyze the effect of hidden gene duplication on the NGS data using the known example of hydin gene. Hydin2 , a duplicated copy of hydin on chromosome 16q22, has been recently found to be localized to chromosome 1q21, and is not included in the current version of standard human genome reference. We found that all of eight personal genome data published so far do not contain hydin2, and there is large number of nsSNPs in hydin. The heterozygosity of those nsSNPs was significantly higher than expected. The sequence coverage depth in hydin gene was about two fold of average depth. We believe that these unique finding of hydin can be used as useful indicators to discover new hidden multiplication in human genome.
Coat Protein Complex I ; Gene Duplication ; Genome ; Genome, Human ; Humans

High-density lipoprotein (HDL) whose primary role is to transport cholesterol from peripheral tissues to the liver, is associated with the incidence of coronary heart disease. We analyzed HDL cholesterol levels in a genetically isolated population of extended Mongolian families. A total of 1002 individuals (54.5% women) from 95 families were enrolled. After genotyping by use of 1000 microsatellite markers, we performed a genome-wide linkage search with variance component analysis. The estimated heritability of HDL cholesterol was 0.45, revealing that HDL cholesterol was under significant genetic influence. We found peak evidence of linkage (LOD score=1.88) for HDL cholesterol level on chromosome 6(nearest marker D6S1660) and potential evidences for linkage on chromosomes 1, 12 and 19 with the LOD scores of 1.32, 1.44 and 1.14, respectively. These results should pave the way for the discovery of the relevant genes by fine mapping and association analysis.
Cholesterol ; Cholesterol, HDL ; Coronary Disease ; Humans ; Incidence ; Lipoproteins ; Liver ; Lod Score ; Microsatellite Repeats ; Mongolia ; Plasma

High-density lipoprotein (HDL) whose primary role is to transport cholesterol from peripheral tissues to the liver, is associated with the incidence of coronary heart disease. We analyzed HDL cholesterol levels in a genetically isolated population of extended Mongolian families. A total of 1002 individuals (54.5% women) from 95 families were enrolled. After genotyping by use of 1000 microsatellite markers, we performed a genome-wide linkage search with variance component analysis. The estimated heritability of HDL cholesterol was 0.45, revealing that HDL cholesterol was under significant genetic influence. We found peak evidence of linkage (LOD score=1.88) for HDL cholesterol level on chromosome 6(nearest marker D6S1660) and potential evidences for linkage on chromosomes 1, 12 and 19 with the LOD scores of 1.32, 1.44 and 1.14, respectively. These results should pave the way for the discovery of the relevant genes by fine mapping and association analysis.
Cholesterol ; Cholesterol, HDL ; Coronary Disease ; Humans ; Incidence ; Lipoproteins ; Liver ; Lod Score ; Microsatellite Repeats ; Mongolia ; Plasma

Vimentin is an intermediate filament that regulates cell attachment and subcellular organization. In this study, vimentin filaments were morphologically altered, and its soluble subunits were rapidly reduced via cadmium chloride treatment. Cadmium chloride stimulated three major mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, and led apoptotic pathway via caspase-9 and caspase-3 activations. In order to determine whether MAPKs were involved in this cadmium-induced soluble vimentin disappearance, we applied MAPK- specific inhibitors (PD98059, SP600125, SB203580). These inhibitors did not abolish the cadmium-induced soluble vimentin disappearance. Caspase and proteosome degradation pathway were also not involved in soluble vimentin disappearance. When we observed vimentin levels in soluble and insoluble fractions, soluble vimentin subunits shifted to an insoluble fraction. As we discovered that heat- shock protein 27 (HSP27) was colocalized and physically associated with vimentin in unstressed cells, the roles of HSP27 with regard to vimentin were assessed. HSP27-overexpressing cells prevented morphological alterations of the vimentin filaments, as well as reductions of soluble vimentin, in the cadmium-treated cells. Moreover, HSP27 antisense oligonucleotide augmented these cadmium-induced changes in vimentin. These findings indicate that HSP27 prevents disruption of the vimentin intermediate filament networks and soluble vimentin disappearance, by virtue of its physical interaction with vimentin in cadmium-treated SK-N-SH cells.
Cadmium/*pharmacology ; Caspases/metabolism ; Cell Line ; Heat-Shock Proteins/*metabolism ; Humans ; Mitogen-Activated Protein Kinases/metabolism ; Protein Binding/drug effects ; Protein Subunits/chemistry/metabolism ; Solubility/drug effects ; Vimentin/*chemistry/*metabolism