• International Journal of Oral Biology
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• 제45권3호
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• pp.84-91
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• 2020

The present study investigated the participation of D-serine and NR2 in antinociception produced by blockade of central erythropoietin-producing hepatocellular carcinoma (Eph) A4 (EphA4) signaling in rats with trigeminal neuropathic pain. Trigeminal neuropathic pain was modeled in male Sprague-Dawley rats using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia, and a miniature dental implant was placed to induce injury to the inferior alveolar nerve. Our current findings showed that nerve injury induced by malpositioned dental implants significantly produced mechanical allodynia; additionally, the inferior alveolar nerve injury increased the expression of D-serine and NR2 subunits in the ipsilateral medullary dorsal horn (trigeminal subnucleus caudalis). Intracisternal administration of EphA4-Fc, an EphA4 inhibitor, inhibited nerve injury-induced mechanical allodynia and upregulated the expression of D-serine and NR2 subunits. Moreover, intracisternal administration of D-amino acids oxidase, a D-serine inhibitor, inhibited trigeminal mechanical allodynia. These results show that D-serine and NR2 subunit pathways participate in central EphA4 signaling after an inferior alveolar nerve injury. Therefore, blockade of D-serine and NR2 subunit pathways in central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3923-3927
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• 2016

Infection with the hepatitis C virus is a major public health concern which can lead to carcinoma and liver failure. It has been shown that single nucleotide polymorphisms can affect the level of gene activity of tumor necrosis factor (TNF) which has an important role, especially in viral infections which can lead to apaptosis of infected hepatocellular cells. We investigated the impact of three possible genotypes for rs1800629 or A/G single nucleotide polymorphism located downstream of $TNF{\alpha}$ gene promoter in groups of control (n=76) and chronic hepatitis C patients (n=89) focusing on the response to treatment among sensitive and resistant groups. Genomic DNA was extracted from $500{\mu}l$ prepheral whole blood and PCR and RFLP were used to amplify the region of interest and genotyping. With statistical analyzes a p-value <0.05 was considered meaningful. There was no significant difference in distribution of possible three genotypes among healthy individuals and patients (P=0.906, OR=1.194, CI=0.063-22.790). However, the frequency of G allele was higher in patients whereas A allele was more common among healthy individuals (p<0.0001). Further studies with more samples seem to be necessary.

• 한국임상약학회지
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• 제26권3호
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• pp.220-229
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• 2016

Background: The treatment goal for patients with chronic hepatitis B infection is to prevent progression of the disease to cirrhosis and hepatocellular carcinoma. Current therapies include standard and pegylated interferon-alfa and nucleoside/nucleotide analogues: lamivudine, adefovir, entecavir, telbivudine, clevudine, and tenofovir. This study aims to analyze changes in the prescribing patterns of chronic hepatitis B (CHB) medications in South Korea between 2013 and 2014. Methods: A cross-sectional study was conducted using National Patients Sample data compiled by the Health Insurance Review and Assessment Service from 2013 and 2014. Patients with CHB were identified with Korean Standard Classification of Diseases code-6 (B18.0 and B18.1) and those who were maintaining active prescriptions with CHB medications covering the index date (December $1^{st}$, each year) were included. The utilization of antiviral therapy was investigated during 2013 and 2014. Results: A total of 4,204 and 4,552 patients in 2013 and 2014 respectively, were included in the analysis. The proportion of male patients was two of third and the patients 41-60 years old accounted for 60% of all analyzed patients. The most utilized drug was entecavir (55.1% in 2013 and 44.8% in 2014) and the second most utilized drug was tenofovir in both years (18.8% in 2013 and 29.0% in 2014). The percentage of combination therapy was 13.6% and 13.1% in 2013 and 2014, respectively. The proportion of tenofovir prescriptions was increased in 2014 compared with 2013. Conclusion: With the development of new drugs and the changes in clinical practice guidelines, the prescription pattern of the antiviral agents for patients with CHB has changed. The rate of utilization of tenofovir has increased.

• Molecular & Cellular Toxicology
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• 제5권1호
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• pp.67-74
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• 2009

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

• Molecular & Cellular Toxicology
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• 제5권2호
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• pp.99-107
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• 2009

Naphthalene is bicyclic aromatic compound that is widely used in various domestic and commercial applications including lavatory scent disks, soil fumigants and moth balls. Exposure to naphthalene results in the development of bronchiolar damage, cataracts and hemolytic anemia in humans and laboratory animals. However, little information is available regarding the mechanism of naphthalene toxicity. We investigated gene expression profiles and potential signature genes in human hepatocellular carcinoma HepG2 cells and human promyelocytic leukemia HL-60 cells after 3 h and 48 h incubation with the IC$_{20}$ and IC$_{50}$ of naphthalene by using 44 k agilent whole human genome oligomicroarray and operon human whole 35 k oligomicroarray, respectively. We identified 616 up-regulated genes and 2,088 down-regulated genes changed by more than 2-fold by naphthalene in HepG2 cells. And in HL-60, we identified 138 up-regulated genes and 182 down-regulated genes changed by more than 2-fold. This study identified several interesting targets and functions in relation to naphthalene-induced toxicity through a gene ontology analysis method. Apoptosis and cell cycle related genes are more commonly expressed than other functional genes in both cell lines. In summary, the use of in vitro models with global expression profiling emerges as a relevant approach toward the identification of biomarkers associated with toxicity after exposure to a variety of environmental toxicants.

• 대한유전성대사질환학회지
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• 제4권1호
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• pp.13-17
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• 2004

저자들은 생후 28일된 발열, 간종대, 출혈성 경향, 구토, 잦은 보챔, 전신의 황달 증상을 보이던 환아를 MS-MS 이용한 신생아 대사 이상 검사와 혈중 아미노산 분석, 뇨중 유기산 분석을 통하여 hereditary tyrosinemia type I으로 진단하였다. 저 페닐알라닌/타이로신 식이와 NTBC 사용으로 국내 첫 타이로신혈증 I 치료 성공례를 경험하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6541-6548
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• 2013

Pigmented rice is mainly black, red, and dark purple, and contains a variety of flavones, tannin, polyphenols, sterols, tocopherols, ${\gamma}$-oryzanols, amino acids, and essential oils. The present study evaluated the cytotoxic effects of purple rice extracts (PREs) combined with chemotherapeutic drugs on human cancer cells and mechanisms of cell death. Methanolic (MeOH) and dichloromethane (DCM) extracts of three cultivars of purple rice in Thailand: Doisaket (DSK), Nan and Payao (PYO), were tested and compared with white rice (KK6). Cytotoxicity was determined by 3-(4, 5-dimethyl)-2, 5-diphenyltetrazolium bromide (MTT) assay in human hepatocellular carcinoma HepG2, prostate cancer LNCaP and murine normal fibroblast NIH3T3 cells. MeOH-PYO-PRE was the most cytotoxic and inhibited HepG2 cell growth more than that of LNCaP cells but was not toxic to NIH3T3 cells. When PREs were combined with paclitaxel or vinblastine, they showed additive cytotoxic effects on HepG2 and LNCaP cells, except for MeOH-PYO-PRE which showed synergistic effects on HepG2 cells when combined with vinblastine. MeOH-PYO-PRE plus vinblastine induced HepG2 cell apoptosis with loss of mitochondrial transmembrane potential (MTP) but no ROS production. MeOH-PYO-PRE-treated HepG2 cells underwent apoptosis via caspase-9 and-3 activation. The level of ${\gamma}$-oryzanol was highest in DCM-PYO-PRE (44.17 mg/g) whereas anthocyanin content was high in MeOH-PYO-PRE (5.80 mg/g). In conclusion, methanolic Payao purple rice extract was mostly toxic to human HepG2 cells and synergistically enhanced the cytotoxicity of vinblastine. Human HepG2 cell apoptosis induced by MeOH-PYO-PRE and vinblastine was mediated through a mitochondrial pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6393-6398
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• 2013

In this research, we used $GdCl_3$ (gadolinium chloride) to restrain the function of Kupffer cells and assessed effects on hepatocarcinogenesis and metastasis in the Kunming mouse. A 0.25% $GdCl_3$ solution (10 mg/kg b.w.) was infused via the vena caudalis of each mouse 1 week before inoculation of H22 cells and was continued once per three days. Then we observed the follow indexes 3 weeks after injection of H22 cells: tumor weight, histologic characteristics of tumor tissue by light microscopy, ultramicrostructure of Kupffer cells under the electron microscope, distribution and number of Kupffer cells by histochemical staining, and TNF-${\alpha}$ and IFN-${\gamma}$ levels in blood-serum and liver tissue by ELISA and RT-PCR. MMP-2 protein expression was tested by immunohistochemistry. The $GdCl_3$ pretreatment had no effect on the quantity of Kupffer cells, but clearly restrained their functions, with decrease of TNF-${\alpha}$ and IFN-${\gamma}$ levels and elevation of MMP2. Tumor immunity functions were markedly suppressed and tumor growth was accelerated with appearance of metastasis. Furthermore, survival time of trial mice was shortened.

• Bulletin of the Korean Chemical Society
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• 제35권8호
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• pp.2335-2341
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• 2014

Chemical investigation on the methanol extract of the starfish Ctenodiscus crispatus resulted in the isolation of five steroids, (22E,$24{\zeta}$)-26,27-bisnor-24-methyl-$5{\alpha}$-cholest-22-en-$3{\beta}$,5,$6{\beta}$,$15{\alpha}$,25-pentol 25-O-sulfate (1), (22E,24R,25R)-24-methyl-$5{\alpha}$-cholest-22-en-$3{\beta}$,5,$6{\beta}$,$15{\alpha}$,25,26-hexol 26-O-sulfate (2), (28R)-24-ethyl-$5{\alpha}$-cholesta-$3{\beta}$,5,$6{\beta}$,8,$15{\alpha}$,28,29-heptaol-24-sulfate (3), (25S)-$5{\alpha}$-cholestane-$3{\beta}$,5,$6{\beta}$,$15{\alpha}$,$16{\beta}$,26-hexaol (4), and ${\Delta}7$-sitosterol (5). Their structures were identified by extensive spectroscopic analyses, including 1D, 2D NMR and MS and chemical methods. Compound 4 showed cytotoxicity against human hepatoma HepG2 and glioblastoma U87MG cells via inhibition of cell growth and induction of apoptosis. Induction of apoptosis by 4 was demonstrated by cell death, DNA fragmentation, increased Bax/Bcl-2 protein ratio and the activation of caspase-3, caspase-9 and poly (ADP-ribose) polymerase (PARP).

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.235-238
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• 2016

Hepatitis C is an ailment of liver caused by hepatitis C virus (HCV) infection. About 3% of the world population is infected by this virus. HCV infection is a leading reason for liver cirrhosis and therefore a major source of hepatocellular carcinoma. The study focused on the incidence of active HCV infection in blood donors of Mardan district of KPK, Pakistan. A total of 5318 blood donors were inspected for the presence of anti-HCV antibodies and HCV-RNA using ICT (immune-chromatographic test), ELISA and RT-PCR at Mardan Medical Complex (MMC), Mardan. Out of these, 157 (2.95%) were positive by ICT, 60 (1.12%) by ELISA and 56 (1.05%) for HCV-RNA. The frequency of active HCV infectivity amongst the blood donors from district Mardan, KPK Pakistan was 1.05 %. Application of strict measures during blood donor selection and use of proper screening assays such as ELISA in place of ICT devices can give a more accurate picture so that the incidence of this viral infection in HCV negative blood recipients can be reduced.