• Title/Summary/Keyword: Therapeutic candidate

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Inhibitory Effects of KM1701 on Airway Cell Infiltration in OVA-Induced Mouse Model (OVA-유도 쥐 모델에서 기도 세포 침윤에 대한 KM1701의 억제효과)

  • Lim, Soon-Min;Choi, Han-Seok;Kim, Sang-Back;Kim, Ye-Jin;Kang, Ki-Sung;Shin, Myoung-Sook;Kim, Kyung-Jun;Hwang, Gwi-Seo;Koo, Bon-Am
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.32 no.2
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    • pp.1-10
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    • 2019
  • Objectives : The objective of present study is to evaluate anti-inflammatory and anti-allergic effects of Perilla(Perilla frutescens; Labiatae, PF), the roots of Peucedanum praeruptorum(PP) and the root of Scutellaria baicalensis(SB) in vitro and anti-asthmatic effects of mixture of PF, PP and SB(PS) on ovalbumin (OVA)-induced asthma in BALB/c mice. Methods : Anti-inflammatory and anti-allergic effects were observed on the lipopolysaccharide(LPS) treated RAW 264.7 cells through Nitric Oxide(NO) production and RBL-2H3 cells through ${\beta}$-hexosaminidase. Anti-asthmatic effects were observed on the number of inflammatory cells in bronchoalveolar lavage fluid(BALF) and the level of IgE in serum on OVA-induced BALB/c mice. Results : The treatment of PF, PP and SB(12.5, 25, 50, $100{\mu}g/m{\ell}$) resulted in a significant inhibition of NO production in RAW 264.7 cells and mast cell degranulation in RBL-2H3 cells. Oral administration of PS(400mg/kg/day) resulted in a significant reduction in the numbers of eosinophils in BALF and level of IgE in serum. Conclusion : The oral administration of PS is effective in ameliorating the eosinophilic infiltration in vivo and thus can be a good therapeutic candidate for allergic asthma.

Vaccinium oldhamii Stems Inhibit Pro-inflammatory Response and Osteoclastogenesis through Inhibition of NF-κB and MAPK/ATF2 Signaling Activation in LPS-stimulated RAW264.7 Cells

  • Park, Su Bin;Kim, Ha Na;Kim, Jeong Dong;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.10a
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    • pp.67-67
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    • 2019
  • Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of ${\alpha}$-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells. Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced $NF-{\kappa}B$ signaling activation through blocking $I{\kappa}B-{\alpha}$ degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

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Cyclodextrins' effect on the enatioseparation of some PPIs and capillary electrophoresis method development for determining rabeprazole enantiomers

  • Choi, Yusung;Pham, Thuy-Vy;Mai, Xuan-Lan;Truong, Quoc-Ky;Le, Thi-Anh-Tuyet;Nguyen, Thi-Ngoc-Van;Lee, Gunhee;Kang, Jong-Seong;Mar, Woongchon;Kim, Kyeong Ho
    • Analytical Science and Technology
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    • v.32 no.5
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    • pp.185-195
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    • 2019
  • Over the past decades, chiral switch of the proton pump inhibitors (PPIs) has been received widespread attention in therapeutic advantages as well as pharmaceutical analysis. In present study, the influence of cyclodextrins (CDs) on the chiral separation of four common PPIs (lansoprazole, omeprazole, pantoprazole, and rabeprazole) was investigated. The results demonstrated that capillary electrophoresis (CE) with dual CDs as a chiral selector system is a possible and promising method for the enantioseparation of these PPIs. Rabeprazole, which is the most challenging and acid-labile candidate among four PPIs, was selected for further development of the technique. To optimize CE condition, the effects of capillary parameters and background electrolytes on the enantioseparation were investigated. Finally, the best chiral separation was acheived by using sulfobutyl ether-${\beta}$-CD, and ${\gamma}$-CD as dual chiral selectors. The developed CE method not only provided the effective chiral separation but also showed the good stability of rabeprazole. The proposed method was successfully validated according to the International Conference on Harmonization guideline and effectively applied to determine rabeprazole enantiomers in commercial rabeprazole tablets, with recoveries ranging from 97.17 % to 103.29 % of the label content.

Elevated plasma α1-antichymotrypsin is a biomarker candidate for malaria patients

  • Young Yil, Bahk;Sang Bong, Lee;Jong Bo, Kim;Tong-Soo, Kim;Sung-Jong, Hong;Dong Min, Kim;Sungkeun, Lee
    • BMB Reports
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    • v.55 no.11
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    • pp.571-576
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    • 2022
  • Advancements in the field of proteomics have provided opportunities to develop diagnostic and therapeutic strategies against various diseases. About half of the world's population remains at risk of malaria. Caused by protozoan parasites of the genus Plasmodium, malaria is one of the oldest and largest risk factors responsible for the global burden of infectious diseases with an estimated 3.2 billion persons at risk of infection. For epidemiological surveillance and appropriate treatment of individuals infected with Plasmodium spp., timely detection is critical. In this study, we used combinations of depletion of abundant plasma proteins, 2-dimensional gel electrophoresis (2-DE), image analysis, LC-MS/MS and western blot analysis on the plasma of healthy donors (100 individuals) and vivax and falciparum malaria patients (100 vivax malaria patients and 8 falciparum malaria patients). These analyses revealed that α1-antichymotrypsin (AACT) protein levels were elevated in vivax malaria patient plasma samples (mean fold-change ± standard error: 2.83 ± 0.11, based on band intensities), but not in plasma from patients with other mosquito-borne infectious diseases. The results of AACT immunoblot analyses showed that AACT protein was significantly elevated in vivax and falciparum malaria patient plasma samples (≥ 2-fold) compared to healthy control donor plasma samples, which has not been previously reported.

Identification and Validation of Novel Biomarkers and Potential Targeted Drugs in Cholangiocarcinoma: Bioinformatics, Virtual Screening, and Biological Evaluation

  • Wang, Jiena;Zhu, Weiwei;Tu, Junxue;Zheng, Yihui
    • Journal of Microbiology and Biotechnology
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    • v.32 no.10
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    • pp.1262-1274
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    • 2022
  • Cholangiocarcinoma (CCA) is a complex and refractor type of cancer with global prevalence. Several barriers remain in CCA diagnosis, treatment, and prognosis. Therefore, exploring more biomarkers and therapeutic drugs for CCA management is necessary. CCA gene expression data was downloaded from the TCGA and GEO databases. KEGG enrichment, GO analysis, and protein-protein interaction network were used for hub gene identification. miRNA were predicted using Targetscan and validated according to several GEO databases. The relative RNA and miRNA expression levels and prognostic information were obtained from the GEPIA. The candidate drug was screened using pharmacophore-based virtual screening and validated by molecular modeling and through several in vitro studies. 301 differentially expressed genes (DEGs) were screened out. Complement and coagulation cascades-related genes (including AHSG, F2, TTR, and KNG1), and cell cycle-related genes (including CDK1, CCNB1, and KIAA0101) were considered as the hub genes in CCA progression. AHSG, F2, TTR, and KNG1 were found to be significantly decreased and the eight predicted miRNA targeting AHSG, F2, and TTR were increased in CCA patients. CDK1, CCNB1, and KIAA0101 were found to be significantly abundant in CCA patients. In addition, Molport-003-703-800, which is a compound that is derived from pharmacophores-based virtual screening, could directly bind to CDK1 and exhibited anti-tumor activity in cholangiocarcinoma cells. AHSG, F2, TTR, and KNG1 could be novel biomarkers for CCA. Molport-003-703-800 targets CDK1 and work as potential cell cycle inhibitors, thereby having potential for consideration for new chemotherapeutics for CCA.

Mixture of Corni Fructus and Schisandrae Fructus improves testosterone-induced benign prostatic hyperplasia through regulating 5α-reductase 2 and androgen receptor

  • Hyun Hwangbo;Min Yeong Kim;Seon Yeong Ji ;Beom Su Park;TaeHee Kim;Seonhye Yoon;Hyunjin Kim;Sung Yeon Kim ;Haeun Jung;Taeiung Kim;Hyesook Lee;Gi-Young Kim;Yung Hyun Choi
    • Nutrition Research and Practice
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    • v.17 no.1
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    • pp.32-47
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    • 2023
  • BACKGROUND/OBJECTIVES: Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosterone-induced BPH. MATERIALS/METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. RESULTS: Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. CONCLUSIONS: Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.

Effect of HTE001, an Herbal Formulation, on Electric Stimulation-induced Penile Erection in Rats (전기 자극으로 유발한 음경 발기력 측정 흰쥐 모델에 대한 HTE001의 발기력 상승효과)

  • Lim, Dong-Wook;Lee, Dong-Hun;Song, Mi-Kyoung;Kim, Mi-Yeon;Bu, Young-Min;Kim, Ho-Cheol
    • The Korea Journal of Herbology
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    • v.24 no.3
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    • pp.139-146
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    • 2009
  • Objectives : This study was conducted to investigate the effect of HTE001, a multi-herbal mixture consisting of 10 herbs, Cornus Frutus, Schizandrae Fructus, Rubi Fructus, Cnidi Fructus, Acanthopanacis senticosi Radix, Cinnamomi Cortex, Eucommiae Cortex, Allii Bulbus, Rehmanniae Radix and Ginseng Radix, on electrostimulation-induced penile erection in rats. Methods : Intracavernous pressure (ICP) and mean arterial blood pressure (MAP) were simultaneously monitored through electric stimulation of the cavernous nerve after the oral administration of HTE001 (30, 100, 300 mg/kg) in normal rats. Statistical analysis was performed on maximal intracavernous pressure (ICP), maximal intracavernous pressure/mean arterial blood pressure (ICP/MAP) ratio, and the area under the curve (AUC) of ICP/MAP ratio. Results : Oral administration of HTE001 300 mg/kg caused the ICP to increase in a frequency-dependent manner. And HTE001 300 mg/kg treatment group showed the highest value in the ICP/MAP ratio and the AUC value of the ICP/MAP ratio compared to the control group at 2 Hz, 6 Hz and 10 Hz, respectively without an effect on the mean arterial blood pressure under the same stimulation of the cavernous nerve. Conclusions : These results show that HTE001 improve penile erection and prolong the decay period in normal rats without affecting mean arterial blood pressure, and suggest that HTE001 could be a good therapeutic candidate to treat erectile dysfunction.

Ubiquitin E3 ligases in cancer: somatic mutation and amplification

  • Eun-Hye Jo;Mi-Yeon Kim;Hyung-Ju Lee;Hee-Sae Park
    • BMB Reports
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    • v.56 no.5
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    • pp.265-274
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    • 2023
  • Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. Nevertheless, tumors depend on residual DNA repair abilities to survive the DNA damage induced by genotoxic stress. This is why only isolated DNA repair signaling is inactivated in cancer cells. DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. DNA DSB repair genes are frequently mutated and amplified in cancer; however, limited data exist regarding the overall genomic prospect and functional result of these modifications. We list the DNA repair genes and related E3 ligases. Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. This study provides a broad list of candidate genes as potential biomarkers for genomic instability and novel therapeutic targets in cancer. As a DSB related proteins considerably appear the possibilities for targeting DNA repair defective tumors or hyperactive DNA repair tumors. Based on recent research, we describe the relationship between unstable DSB repairs and DSB-related E3 ligases.

Overviews on the Clinical Use of Stem Cells in Orthopaedics (근골격계에서 줄기세포를 이용한 재생치료의 개관)

  • Im, Gun-Il
    • Journal of the Korean Orthopaedic Association
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    • v.54 no.6
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    • pp.475-477
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    • 2019
  • Stem cell research arose from the need to explore new therapeutic possibilities for intractable and lethal diseases. Although musculoskeletal disorders are basically nonlethal, their high prevalence and the relative ease of performing clinical trials have facilitated the clinical application of stem cells in this field. On the other hand, despite the plethora of in vitro and preclinical studies in stem cell research for regenerative medicine in the musculoskeletal system, few reliable clinical studies have been published. Stem cell therapy can be applied locally for bone, cartilage, and tendon regeneration. The candidate disease modalities in bone regeneration include large bone defects, nonunion of fractures, and osteonecrosis. Focal osteochondral defect and osteoarthritis are the current targets for cartilage regeneration. For tendon regeneration, bone-tendon junction problems, such as rotator cuff tears are hot topics in clinical research. To date, the literature supporting stem cell-based therapies comprises mostly case reports or case series.

Effects of Green Tea Extract Diet on the Phospholipid Content of Aluminum-Induced-Damaged Cerebral Tissue of Old Rats (노령 흰쥐의 대뇌 조직에서 알루미늄 투여에 대한 녹차 추출물이 인지질 함량에 미치는 효과)

  • Jung, Young-Hee;Han, Sung-Hee
    • Journal of the Korean Society of Food Culture
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    • v.25 no.2
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    • pp.232-239
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    • 2010
  • This study was designed to investigate the effects of green tea extract on aluminum-induced damage to phospholipid content in old rat cerebral tissue. The aim of this study was to investigate the possibility that aluminum is the cause of Alzheimer's disease. Forty Sprague-Dawley old male rats weighing 350$\pm$10 g were divided into four groups, consisting of a control group (CON), 40 ppm aluminum sulfate group (Al-40), green tea water extract group (GTWE), and 40 ppm aluminum sulfate and green tea water extract groups (Al-40+GTWE) and kept on their respective diets for 12 weeks. In order to discover the influence of aluminum on cerebral tissue of old male rats, the serum aluminum concentration and phospholipid composition were compared between the aluminum-treated group and the normal group. The results showed that the serum aluminum concentration was higher in the aluminum sulfate-treated group than in the normal group. The cerebral tissue phospholipid concentration decreased significantly in the aluminum sulfate treated group as compared to the normal group. The results of this experiment show that increase of aluminum concentration in experimental animals causes the rise of serum aluminum and phospholipid concentrations, phenomena that are very similar to those shown in Alzheimer's disease., The results of this experiment, together with reports that aluminum is a cause of neurofibrillary tangles in cerebral tissue, therefore demonstrate the possibility that aluminum is the cause of Alzheimer's disease. Green tea water extract is also shown to be an effective therapeutic candidate for the treatment of Alzheimer's disease.