• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.239-245
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• 1997

Trimetoquinol (TMQ) and its analogs are known to have thromboxane $A_2$ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS 386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited $Ca^{2+}$ -induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound\`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to $\alpha$-adrenergic receptor. Taken together. we concluded that the mechamism of action of GS283 and GS86 is not related with in TXA$_2$ receptor but concerned with calcium antagonistic action and a-blocking action.n.

• The Journal of Internal Korean Medicine
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• v.43 no.6
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• pp.1162-1185
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• 2022

Purpose: We examined the effects of Dansam (Salvia miltiorrhiza Bunge, SM) and Dansam-eum (DSE) on gastroesophageal reflux disease (GERD) and reflux esophagitis by comparing the inhibitory effects of SM and DSE with the representative treatment of PPI Omeprazole to determine if the effects of the prescription DSE based on Korean medicine are better than those of a single-use of SM. Methods: We performed experiments using both animal models and cancer cells. Results: Comparison of SM and DSE with PPI in the animal model tests revealed that the effects were superior for SM and DSE than for PPI in all categories (8-OHdG, p-IκB, PAR2, COX-1, cathelicidin, p-JNK, Caspase 3, ATP6V1B1, GRPR, serotonin, and NPY). In three categories (COX-1, serotonin, and NPY), SM and DSE showed superior results over the Controls. In the animal model tests, DSE was superior to SM in all categories except for serotonin. The anti-cancer effects observed in cancer cell tests revealed that SM and DSE had meaningful results in terms of cytotoxicity and cell movement rate, as well as in cancer cell apoptosis. Conclusions: We confirmed that SM and DSE can have effects on reflux esophagitis through the regulation of oxidative stress, inflammation, mucosal protection, apoptosis, proton pumping, and the enteroendocrine system in the stomach and esophagus. We also confirmed that SM and DSE have superior effects to those of PPI on all aspects, especially gastric mucosa protection and enteroendocrine system control. We also confirmed that SM and DSE have anti-cancer effects. Above all, we confirmed that DSE has superior effects on almost all aspects compared to using SM alone.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.200-209
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• 2023

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resistance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunction, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.112-112
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• 2002

Under normal conditions, women produce a single dominant follicle that participates in a single ovuation each menstrual cycle. But Polycystic ovary syndrome(PCOS) conditions, folliculogenesis does not proceed normally. This condition leads to the accumlation of large numbers of small graffian follicles in which the theca interstitial cells (TIC) produce abnormally large amounts of androgen. PCOS is probably the most common endocrine disorder, affecting women of reprodutive age with 5-10% prevalence estimate. Chronic anovulation, hyperandrogenism, hirsutism, obesity, infertility and polycystic ovaries are clinical hallmarks of women with PCOS. Its etiology remains unknown. To investigate the gene expression pattern of ovary in PCO-induced rat, we used cDNA expression analysis. Total RNA was extracted from the ovary of PCO-induced rat and reverse-transcribed in the presence of［$\alpha$$^{32}$P］-dATP Which were hybridized to Atlas$^{TM}$ Rat Toxicology 1.2 array (Clontech) representing approximately 1176 rat genes. We compared gene expression between ovary of pco-induced immature female rats and control. Differential gene expression profiles were revealed (LIFR-alpha, ADRA1A, Heat shock 90-kDa protein A, PDGFRA). Reverse transcription-polymerase chain reaction(RT-PCR) was used to validate the relative expression pattern obtained by the cDNA array. The precise relationship between the altered expression of genes and PCO is a matter of further investigation. This study was supported by Korea Science and Engineering Foundation(KOSEF)

• Journal of Animal Science and Technology
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• v.65 no.2
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• pp.401-411
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• 2023

Many studies have been conducted to improve technology for semen cryopreservation in pigs. However, computer-assisted analysis of sperm motility and morphology is insufficient to predict the molecular function of frozen-thawed semen. More accurate expression patterns of boar sperm proteins may be derived using the isobaric tags for relative and absolute quantification (iTRAQ) technique. In this study, the iTRAQ-labeling system was coupled with liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis to identify differentially expressed CM10-fractionated proteins between fresh and frozen-thawed boar semen. A total of 76 protein types were identified to be differentially expressed, among which 9 and 67 proteins showed higher and lower expression in frozen-thawed than in fresh sperm samples, respectively. The classified functions of these proteins included oxidative phosphorylation, mitochondrial inner membrane and matrix, and pyruvate metabolic processes, which are involved in adenosine triphosphate (ATP) synthesis; and sperm flagellum and motile cilium, which are involved in sperm tail structure. These results suggest a possible network of biomarkers associated with survival after the cryopreservation of Duroc boar semen.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.40-47
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• 2023

Activation of the NLRP3 inflammasome is a necessary process to induce fibrosis in nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is a kind of NAFLD that encompasses the spectrum of liver disease. It is characterized by inflammation and ballooning of hepatocytes during steatosis. We tested whether inhibiting the NLRP3 inflammasome could prevent the development and pathology of NASH. We identified loganin as an inhibitor of the NLRP3 inflammasome and investigated whether in vivo administration of loganin prevented NASH symptoms using a methionine-choline deficient (MCD) diet model in mice. We found that loganin inhibited the NLRP3 inflammasome activation triggered by ATP or nigericin, as shown by suppression of the production of interleukin (IL)-1β and caspase-1 (p10) in mouse primary macrophages. The speck formation of apoptosisassociated speck-like protein containing a caspase recruitment domain (ASC) was blocked by loganin, showing that the assembly of the NLRP3 inflammasome complex was impaired by loganin. Administration of loganin reduced the clinical signs of NASH in mice fed the MCD diet, including hepatic inflammation, fat accumulation, and fibrosis. In addition, loganin reduced the expression of NLRP3 inflammasome components in the liver. Our findings indicate that loganin alleviates the inflammatory symptoms associated with NASH, presumably by inhibiting NLRP3 inflammasome activation. In summary, these findings imply that loganin may be a novel nutritional and therapeutic treatment for NASH-related inflammation.

• Korean journal of applied entomology
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• v.62 no.2
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• pp.83-87
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• 2023

Nysius plebeius is a major lygaeid pest of various cereal crops and ornamental plants in East Asian countries, including Korea. The complete mitochondrial genome of N. plebeius was characterized and found to comprise a total of 17,367 bp, which included 13 protein-coding genes, NADH dehydrogenase components (complex I, ND), cytochrome oxidase subunits (complex VI, COX), cytochrome oxidase b (CYPB), two ATP synthases, two ribosomal RNA genes, and 22 transfer RNAs. The GC content of 23%. It showed high sequence similarity to other Lygaeidae species, such as N. cymoides (94.5%), N. fuscovittatus (91.7%), and an unknown Nysius species (94.1%). This new N. plebeius mitochondrial genome can be widely used for evolutionary studies of Lygaeidae and to improve pest management practices.

• The Plant Pathology Journal
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• v.39 no.2
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• pp.191-206
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• 2023

Ground cherry (Physalis pubescens) is the most prominent species in the Solanaceae family due to its nutritional content, and prospective health advantages. It is grown all over the world, but notably in northern China. In 2019 firstly bacterial leaf spot (BLS) disease was identified on P. pubescens in China that caused by both BLS pathogens Xanthomonas euvesicatoria pv. euvesicatoria resulted in substantial monetary losses. Here, we compared whole genome sequences of X. euvesicatoria to other Xanthomonas species that caused BLS diseases for high similarities and dissimilarities in genomic sequences through average nucleotide identity (ANI) and BLAST comparison. Molecular techniques and phylogenetic trees were adopted to detect X. euvesicatoria on P. pubescens using recQ, hrpB1, and hrpB2 genes for efficient and precise identification. For rapid molecular detection of X. euvesicatoria, loop-mediated isothermal amplification, polymerase chain reaction (PCR), and real-time PCR techniques were used. Whole genome comparison results showed that the genome of X. euvesicatoria was more closely relative to X. perforans than X. vesicatoria, and X. gardneri with 98%, 84%, and 86% ANI, respectively. All infected leaves of P. pubescens found positive amplification, and negative controls did not show amplification. The findings of evolutionary history revealed that isolated strains XeC10RQ, XeH9RQ, XeA10RQ, and XeB10RQ that originated from China were closely relative and highly homologous to the X. euvesicatoria. This research provides information to researchers on genomic variation in BLS pathogens, and further molecular evolution and identification of X. euvesicatoria using the unique target recQ gene through advance molecular approaches.

• International Journal of Industrial Entomology and Biomaterials
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• v.46 no.2
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• pp.41-54
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• 2023

The blue-tailed damselfly, Ischnura elegans Van der Linden, 1820 (Odonata: Coenagrionidae), is a climate-sensitive indicator species in South Korea. In this study, we sequenced the complete mitochondrial genome (mitogenome) of I. elegans collected from South Korea for subsequent population genetic analysis, particularly to trace population movements in response to climate change. The 15,963 base pair (bp)-long complete mitogenome of I. elegans has typical sets of genes including a major non-coding region (the A+T-rich region), and an arrangement identical to that observed in ancestral insect species. The ATP6, ND3 and ND1 genes have the TTG start codon, which, although rare, is the canonical start codon for animal mitochondrial tRNA. The A/T content was 71.4% in protein-coding genes, 72.1% in tRNAs, 72.9% in the whole genome, 74.7% in srRNA, 75.3% in lrRNA, and 83.8% in the A+T-rich region. The A+T-rich region is unusually long (1,196 bp) and contains two subunits (192 bp and 176-165 bp), each of which is tandemly triplicated and surrounded by non-repeat sequences. Comparison of the sequence divergence among available mitogenomes of I. elegans, including the one from the current study, revealed ND2 as the most variable gene, followed by COII and COI, suggesting that ND2 should be targeted first in subsequent population-level studies. Phylogenetic reconstruction based on all available mitogenome sequences of Coenagrionidae showed a strong sister relationship between I. elegans and I. senegalensis.

• Molecules and Cells
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• v.46 no.4
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• pp.219-230
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• 2023

Down syndrome (DS) is the most common autosomal aneuploidy caused by trisomy of chromosome 21. Previous studies demonstrated that DS affected mitochondrial functions, which may be associated with the abnormal development of the nervous system in patients with DS. Runt-related transcription factor 1 (RUNX1) is an encoding gene located on chromosome 21. It has been reported that RUNX1 may affect cell apoptosis via the mitochondrial pathway. The present study investigated whether RUNX1 plays a critical role in mitochondrial dysfunction in DS and explored the mechanism by which RUNX1 affects mitochondrial functions. Expression of RUNX1 was detected in induced pluripotent stem cells of patients with DS (DS-iPSCs) and normal iPSCs (N-iPSCs), and the mitochondrial functions were investigated in the current study. Subsequently, RUNX1 was overexpressed in N-iPSCs and inhibited in DS-iPSCs. The mitochondrial functions were investigated thoroughly, including reactive oxygen species levels, mitochondrial membrane potential, ATP content, and lysosomal activity. Finally, RNA-sequencing was used to explore the global expression pattern. It was observed that the expression levels of RUNX1 in DS-iPSCs were significantly higher than those in normal controls. Impaired mitochondrial functions were observed in DS-iPSCs. Of note, overexpression of RUNX1 in N-iPSCs resulted in mitochondrial dysfunction, while inhibition of RUNX1 expression could improve the mitochondrial function in DS-iPSCs. Global gene expression analysis indicated that overexpression of RUNX1 may promote the induction of apoptosis in DS-iPSCs by activating the PI3K/Akt signaling pathway. The present findings indicate that abnormal expression of RUNX1 may play a critical role in mitochondrial dysfunction in DS-iPSCs.