• Asian-Australasian Journal of Animal Sciences
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• v.20 no.11
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• pp.1662-1669
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• 2007

The high mobility group AT-hook1 (HMGA1) proteins are known to be related to the regulation of gene transcription, replication and promotion of metastatic progression in cancer cells. The loss of expression by disrupting the HMGA1 gene affects insulin signaling and causes diabetes in the mouse. Previously identified single nucleotide polymorphism (SNP) of HMGA1 was significantly associated with fat deposition traits in the pig. In this study, we identified 3,935 bp nucleotide sequences from exon 5 to exon 8 of the bovine HMGA1 gene and its mRNA expression was observed by quantitative real-time PCR. Six single nucleotide polymorphisms in the bovine HMGA1 gene were detected and the allele frequencies of these SNPs were investigated using the PCR-RFLP method in nine cattle breeds including Limousin, Simmental, Brown Swiss, Hereford, Angus, Charolais, Hanwoo, Brahman and Red Chittagong cattle. The map location showed that the bovine HMGA1 gene was also closely located with a previously identified meat quality QTL region indicating this gene is the most likely positional candidate for meat quality traits in cattle.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.11-18
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• 2020

Background: Nivolumab and pembrolizumab are antagonists of the programmed death-ligand 1 (PD-L1) receptor that function as immuno-oncological agents. This study aimed to evaluate the safety and efficacy of nivolumab and pembrolizumab in elderly patients in outpatient settings. Methods: The safety and efficacy of nivolumab and pembrolizumab were compared retrospectively among patients at the Veterans Health Service (VHS) Medical Center in Seoul, South Korea, from September 1, 2017 to August 25, 2018. Results: Eighty-seven patients were selected for the study. The median progression-free survival was 63 days for nivolumab (95% confidence interval (CI), [14 to 282]) vs. 243 days for pembrolizumab (95% CI, [22 to 348]) (p =0.04). The objective response rate (ORR) was 0% in the nivolumab group vs 5.6% in the pembrolizumab group (p =0.310). All the patients exhibited treatment-related adverse effects. More than 89% of the patients exhibited diseases of the gastrointestinal (GI) tract. Pneumonia, of grades three or higher, was the most common adverse effect, followed by weakness and anorexia. Conclusions: There was no statistically significant difference between the nivolumab group and the pembrolizumab group with respect to the ORR. The incidence and severity of the adverse effects in this study were higher than those of previous studies; however, these adverse effects are generally manageable in a real-world clinical setting. Further randomized controlled studies will be necessary to confirm these results in elderly patients.

• Journal of Pharmacopuncture
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• v.9 no.3 s.21
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• pp.147-154
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• 2006

Objectives : The focus of the analysis was laid on changes in research pertaining to pharmacopuncture in regards to time progression. Methods : Type analysis was done on pharmacopuncture related papers published in the Journal of Korean Institute of Pharmacopuncture from the inaugural issue to June 2006 issue. 196 papers are analyzed to the sort of type. Results : For type analysis of the type of studies, experiment papers outnumbered other types with 94 cases, followed by 67 for clinical trials, and 35 for literary studies. Type analysis on the type of illnesses listed in the Methods section, 31 papers concentrated on arthritis or HIVD of spine, 6 for Pharmacopuncture response in human, 5 for anti-cancer and immune disorders, etc. Conclusion : Since its inaugural issue in 1997 to August 2006 issue ranging 10 years, type analysis revealed that the number of journals pertaining to pharmacopuncture has risen steadily over the years and nearly half of papers published recently are dealing with pharmacopuncture. Pharmacopuncture is a treatment method based on the unique theory of Korean traditional medicine. Its superior efficacy is proven through numerous research works, and effort and academical approach on pharmacopuncture are expected to receive positive evaluation.

• Toxicological Research
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• v.34 no.4
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• pp.291-296
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• 2018

Chemical carcinogenesis is a multistep process. Genotoxic carcinogens, which are DNA-reactive, induce DNA adduct formation and genetic alterations in target cells, thereby generating mutated cells (initiation). Subsequently, preneoplastic lesions appear through clonal proliferation of the mutated cells and transform into tumors (promotion and progression). Many factors may influence these processes in a dose-dependent manner. Therefore, quantitative analysis plays an important role in studies on the carcinogenic threshold of genotoxic carcinogens. Herein, we present data on the relationship between key carcinogenic events and their deriving point of departure (PoD). Their PoDs were also compared to those of the carcinogenesis pathway. In an experiment, the liver of rats exposed to 2-amino-3,8-dimethylimidazo-(4,5-f)quinoxaline (MeIQx) was examined to determine the formation of MeIQx-DNA adducts, generation of mutations at LacI transgene, and induction of preneoplastic glutathione S-transferase placental form (GST-P)-positive foci and tumors (benign and malignant). The PoDs of the above key events in the carcinogenicity of MeIQx were increased as the carcinogenesis advanced; however, these PoDs were lower than those of tumor induction. Thus, the order of key events during tumor induction in the liver was as follows: formation of DNA adducts ${\ll}$ Mutations ${\ll}$ GST-positive foci (preneoplasia) ${\ll}$ Tumor (adenoma and carcinoma). We also obtained similar data on the genotoxic and carcinogenic PoDs of other hepatocarcinogens, such as 2-amino-3,8-dimethylimidazo(4,5-f)quinoline. These results contribute to elucidating the existence of a genotoxic and carcinogenic threshold.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.519-527
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• 2017

Excessive activation of microglia causes the continuous production of neurotoxic mediators, which further causes neuron degeneration. Therefore, inhibition of microglial activation is a possible target for the treatment of neurodegenerative disorders. Balanophonin, a natural neolignoid from Firmiana simplex, has been reported to have anti-inflammatory and anti-cancer effects. In this study, we aimed to evaluate the anti-neuroinflammatory effects and mechanism of balanophonin in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. BV2 microglia cells were stimulated with LPS in the presence or absence of balanophonin. The results indicated that balanophonin reduced not only the LPS-mediated TLR4 activation but also the production of inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), $Interleukin-1{\beta}$ ($IL-1{\beta}$), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), in BV2 cells. Balanophonin also inhibited LPS-induced inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) protein expression and mitogen activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 MAPK. Interestingly, it also inhibited neuronal cell death resulting from LPS-activated microglia by regulating cleaved caspase-3 and poly ADP ribose polymerase (PARP) cleavage in N2a cells. In conclusion, our data indicated that balanophonin may delay the progression of neuronal cell death by inhibiting microglial activation.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.233-240
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• 2020

Autophagy regulators are often effective as potential cancer therapeutic agents. Here, we investigated paclitaxel sensitivity in cells with knockout (KO) of ATG5 gene. The ATG5 KO in multidrug resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr) was generated using the CRISPR/Cas9 technology. The qPCR and LC3 immunoblot confirmed knockout of the gene and protein of ATG5, respectively. The ATG5 KO restored the sensitivity of Ras-NIH 3T3/Mdr cells to paclitaxel. Interestingly, ATG5 overexpression restored autophagy function in ATG5 KO cells, but failed to rescue paclitaxel resistance. These results raise the possibility that low level of resistance to paclitaxel in ATG5 KO cells may be related to other roles of ATG5 independent of its function in autophagy. The ATG5 KO significantly induced a G₂/M arrest in cell cycle progression. Additionally, ATG5 KO caused necrosis of a high proportion of cells after paclitaxel treatment. These data suggest that the difference in sensitivity to paclitaxel between ATG5 KO and their parental MDR cells may result from the disparity in the proportions of necrotic cells in both populations. Thus, our results demonstrate that the ATG5 KO in paclitaxel resistant cells leads to a marked G₂/M arrest and sensitizes cells to paclitaxel-induced necrosis.

• Journal of Microbiology and Biotechnology
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• v.18 no.8
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• pp.1427-1430
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• 2008

Decursinol, found in the roots of Angelica gigas Nakai, has been traditionally used to treat anemia and other various diseases. Recently, numerous biological activities such as cytotoxic effect on leukemia cells, and antitumor, neuroprotection, and antibacterial activities have been reported for this compound. Although a number of proteins including protein kinase C, androgen receptor, and acetylcholinesterase were proposed as molecular targets responsible for the activities of decursinol, they are not enough to explain such a diverse biological activity mentioned above. In this study, we employed a chemical proteomic approach, leading to identification of seven proteins as potential proteins interacting with decursinol. Most of the proteins contain a defined ATP or nucleic acid binding domain and have been implied to be involved in the pathogenesis and progression of various human diseases including cancer, autoimmune disorders, or neurodegenerative diseases. The present results may provide clues to understand the molecular mechanism of the biological activities shown by decursinol, an anticancer natural product.

• Journal of Microbiology and Biotechnology
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• v.27 no.6
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• pp.1163-1170
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• 2017

Clostridium difficile releases two exotoxins, toxin A and toxin B, which disrupt the epithelial cell barrier in the gut to increase mucosal permeability and trigger inflammation with severe diarrhea. Many studies have suggested that enteric nerves are also directly involved in the progression of this toxin-mediated inflammation and diarrhea. C. difficile toxin A is known to enhance neurotransmitter secretion, increase gut motility, and suppress sympathetic neurotransmission in the guinea pig colitis model. Although previous studies have examined the pathophysiological role of enteric nerves in gut inflammation, the direct effect of toxins on neuronal cells and the molecular mechanisms underlying toxin-induced neuronal stress remained to be unveiled. Here, we examined the toxicity of C. difficile toxin A against neuronal cells (SH-SY5Y). We found that toxin A treatment time- and dose-dependently decreased cell viability and triggered apoptosis accompanied by caspase-3 activation in this cell line. These effects were found to depend on the up-regulation of reactive oxygen species (ROS) and the subsequent activation of p38 MAPK and induction of $p21^{Cip1/Waf1}$. Moreover, the N-acetyl-$\text\tiny L$-cysteine (NAC)-induced down-regulation of ROS could recover the viability loss and apoptosis of toxin A-treated neuronal cells. These results collectively suggest that C. difficile toxin A is toxic for neuronal cells, and that this is associated with rapid ROS generation and subsequent p38 MAPK activation and $p21^{Cip1/Waf1}$ up-regulation. Moreover, our data suggest that NAC could inhibit the toxicity of C. difficile toxin A toward enteric neurons.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.113-125
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• 2018

Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells. Theragnosis is a concept in next-generation medicine that simultaneously combines accurate diagnostics with therapeutic effects. Molecular components in exosomes have been found to be related to certain diseases and treatment responses, indicating that they may have applications in diagnosis via molecular imaging and biomarker detection. In addition, recent studies have reported that exosomes have immunotherapeutic applications or can act as a drug delivery system for targeted therapies with drugs and biomolecules. In this review, we describe the formation, structure, and physiological roles of exosomes. We also discuss their roles in the pathogenesis and progression of diseases including neurodegenerative diseases, cardiovascular diseases, and cancer. The potential applications of exosomes for theragnostic purposes in various diseases are also discussed. This review summarizes the current knowledge about the physiological and pathological roles of exosomes as well as their diagnostic and therapeutic uses, including emerging exosome-based therapies that could not be applied until now.

• Journal of Korean Neurosurgical Society
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• v.40 no.5
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• pp.342-345
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• 2006

Objective : Gamma Knife Surgery[GKS] for the management of pineal region tumors is challengeable strategy as direct access to this area is not easy. The experiences of pineal region tumor patients treated with GKS were analyzed to evaluate the effectiveness. Methods : Seven patients with tumors in the pineal region were treated with GKS between September 1998 and May 2005. The histological diagnosis were pineal parenchymal tumor [2 patients], low-grade astrocytoma [2 patients], immature teratoma [1 patient], and choriocarninoma [1 patient]. One patient was diagnosed as metastatic brain tumor based on histological diagnosis for primary site and brain imaging study. The median marginal dose was 15Gy [range; $11{\sim}20$] at the 50% isodose line. The median target volume was $2.5cm^3$ [range; $0.8{\sim}12.5$]. The median clinical follow up period was 29 months [range; $13{\sim}93$] and the median radiological follow up period was 18 months [range; $6{\sim}73$]. Results : Tumor volume measured in follow-up images showed reduction in six patients, disappearance in one. No adverse effect due to GKS was found during the follow-up period. The performance status was preserved in all patients except one who died due to progression of primary cancer in spite of controlled metastatic brain lesion. Conclusion : Gamma Knife Surgery can be applied to pineal region tumors irrespective of their histology whenever surgery is not indicated.