• Title/Summary/Keyword: Drug-associated

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Arctigenin Inhibits Etoposide Resistance in HT-29 Colon Cancer Cells during Microenvironmental Stress

  • Yoon, Sae-Bom;Park, Hae-Ryong
    • Journal of Microbiology and Biotechnology
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    • v.29 no.4
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    • pp.571-576
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    • 2019
  • Microenvironmental stress, which is naturally observed in solid tumors, has been implicated in anticancer drug resistance. This tumor-specific stress causes the degradation of topoisomerase $II{\alpha}$, rendering cells resistant to topoisomerase $II{\alpha}$-targeted anticancer agents. In addition, microenvironmental stress can induce the overexpression of 78kDa glucose regulated protein (GRP78), which can subsequently block the activation of apoptosis induced by treatment with anticancer agents. Therefore, inhibition of topoisomerase $II{\alpha}$ degradation and reduction in GRP78 expression may be effective strategies for inhibiting anticancer drug resistance. In this study, we investigated the active compound arctigenin, which inhibited microenvironmental stress-induced etoposide resistance in HT-29 cells. Arctigenin was also highly toxic to etoposide-resistant HT-29 cells, with an $IC_{50}$ value of $10{\mu}M$ for colony formation. We further showed that arctigenin inhibited the degradation of topoisomerase $II{\alpha}$ and reduced the expression of GRP78. Thus, these results suggest that arctigenin is a novel therapeutic agent that inhibits resistance to etoposide associated with microenvironmental stress conditions.

Risk Factors of Gastrointestinal Bleeding in Patients Receiving New Oral Anticoagulants (New Oral Anticoagulants를 복용하는 환자들에서 위장관 출혈의 위험인자)

  • Lee, Ju Yup
    • The Korean journal of helicobacter and upper gastrointestinal research
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    • v.18 no.4
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    • pp.219-224
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    • 2018
  • New oral anticoagulants (NOACs) are now widely used for the prevention and treatment of venous thrombosis, and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. As compared with warfarin, NOACs have the advantage of rapid onset of action and less drug interaction. However, they carry a higher risk of gastrointestinal (GI) bleeding than warfarin. The risk of GI bleeding in patients using NOACs varies according to the type and dose of the drug. By contrast, apixaban and edoxaban are reported to carry similar risks as warfarin, and the risks with dabigatran and rivaroxaban are higher than that with warfarin. In patients using NOACs, old age, impaired renal function, impaired liver function, concurrent use of antiplatelet agents, and nonsteroidal anti-inflammatory drugs are considered major risk factors of GI bleeding, and gastroprotective agents such as histamine-2 receptor antagonist and proton pump inhibitor have preventive effects. To prevent GI bleeding associated with NOACs, the characteristics of each NOAC and the risk factors of bleeding should be recognized.

Cardiac Safety Assessment of Medicinal Herbal Formulas Using hERG-HEK 293 cell (hERG 칼륨 채널 매개성 HEK 293 세포를 이용한 한약 처방의 심장 독성 평가 연구)

  • Choi, Susanna;Kwon, Oh-Bin;Lee, SION;Seo, Chang-Seob;Shin, Hyeun-Kyoo
    • The Journal of Korean Medicine
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    • v.40 no.2
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    • pp.94-105
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    • 2019
  • Objectives: The correlation between medicinal herbal formulas and a risk of cardiotoxicity has been controversial. Thus, this study investigated cardiac safety assessment of 52 most commonly used medicinal herbal formulas. Methods: We evaluated the in vitro effects of medicinal herbal formulas on recombinant human embryonic kidney 293 (HEK 293) cell line expressing human ether-a-go-go-related gene (hERG) potassium channel. Results and Conclusion: Our results demonstrated that all of 52 medicinal herbal formulas did not show inhibition of hERG current in hERG-HEK 293 recombinant cells. In conclusion, these safety data suggest that 52 medicinal herbal formulas were not associated with an increased risk of cardiotoxicity in hERG-HEK 293 recombinant cells.

Factors affecting Unintentional Injuries at School: Focused on Violence (학교 내 손상에 미치는 영향 요인: 학교 폭력 경험을 중심으로)

  • Kwon, Min;Nam, Eunjeong;Lee, Jinhwa
    • Journal of the Korean Society of School Health
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    • v.33 no.3
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    • pp.139-147
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    • 2020
  • Purpose: The study aimed to identify factors affecting unintentional injuries at school focusing on violent experiences in adolescents. Methods: The study used the raw data of the Korea Youth Risk Behavior Web-based Survey (2019). A total of 60,040 students were included in the analysis. Descriptive statistics, χ2 test, and multiple logistic regression were performed, using SPSS version 25.0. General characteristics, gender, school, academic achievement, living with family, socioeconomic status, vigorous physical activity, perceived stress, sleep satisfaction, high caffeine drinking, risky alcohol drinking, smoking, sexual experience, drug use, and safety education, were adjusted for and the relationship between unintentional injuries and violence was analyzed. Results: The results showed 2.4% of the adolescents had experienced violence and 24.7% had suffered unintentional injuries. Violent experiences had a significant effect on unintentional injuries among adolescents. Injuries were 1.93 times higher among adolescents who had experienced violence. Gender, school levels, high-intensity physical activity, stress, sleep satisfaction, high caffeine drinks, dangerous drinking, drug use, and safety education were associated with unintentional injuries among adolescents. Conclusion: Adolescents at high risk of suffering violence and injuries should be identified and assessed preemptively. In addition, it is necessary to implement systematic school health-centered safety education programs in order to prevent violence and injuries.

Discovery of Anticancer Activity of Amentoflavone on Esophageal Squamous Cell Carcinoma: Bioinformatics, Structure-Based Virtual Screening, and Biological Evaluation

  • Chen, Lei;Fang, Bo;Qiao, Liman;Zheng, Yihui
    • Journal of Microbiology and Biotechnology
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    • v.32 no.6
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    • pp.718-729
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    • 2022
  • Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy with poor prognosis. Here, due to the necessity for exploring potential therapies against ESCC, we obtained the gene expression data on ESCC from the TCGA and GEO databases. Venn diagram analysis was applied to identify common targets. The protein-protein interaction network was constructed by Cytoscape software, and the hub targets were extracted from the network via cytoHubba. The potential hub nodes as drug targets were found by pharmacophore-based virtual screening and molecular modeling, and the antitumor activity was evaluated through in vitro studies. A total of 364 differentially expressed genes (DEGs) in ESCC were identified. Pathway enrichment analyses suggested that most DEGs were mainly involved in the cell cycle. Three hub targets were retrieved, including CENPF, CCNA2 (cyclin A), and CCNB1 (cyclin B1), which were highly expressed in esophageal cancer and associated with prognosis. Moreover, amentoflavone, a promising drug candidate found by pharmacophore-based virtual screening, showed antiproliferative and proapoptotic effects and induced G1 in esophageal squamous carcinoma cells. Taken together, our findings suggested that amentoflavone could be a potential cell cycle inhibitor targeting cyclin B1, and is therefore expected to serve as a great therapeutic agent for treating esophageal squamous cell carcinoma.

Safety of hydroxyzine in the sedation of pediatric dental patients

  • Taegyeom, Kim;Keoungah, Kim;Seungoh, Kim;Jongbin, Kim
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.22 no.6
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    • pp.395-404
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    • 2022
  • Hydroxyzine is one of the most popular oral sedatives used in pediatric dentistry. This study aimed to investigate the safety and possible side effects of sedation using hydroxyzine in pediatric dentistry. "Hydroxyzine," "Dental sedation," "Child," and "Safety" and their associated synonyms were searched using the Cochrane Library, Embase, PubMed, KISS, KMBASE, and KoreaMed databases. Academic information and portals of DBpia and RISS were also perused. Altogether, 340 papers were found, among which a total of 24 papers were selected according to the detailed criteria. Nine studies used hydroxyzine as monotherapy, and 10 studies compared its safety when hydroxyzine used as multitherapy. In addition, seven studies employed a drug regimen wherein hydroxyzine was one of the components. All these studies revealed that the adverse events specific to hydroxyzine usage were drowsiness and dryness of the mouth, and that there were respiratory complications due to a synergistic reaction of hydroxyzine. Although classified as a histamine blocker, hydroxyzine with its sedative, antiemetic, anticonvulsant, and anticholinergic properties is an oral sedative available without serious adverse events, If the proper dosage of the drug is used and its synergistic effects with other drugs are ascertained in the route of administration.

Radiographic changes of mandibular cortical bone in bisphosphonate drug holiday

  • Lee, Dae-Hoon;Seo, Ja-In;Song, Seung-Il;Lee, Jeong-Keun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.48 no.4
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    • pp.219-224
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    • 2022
  • Objectives: There have been few studies to date on the residual effect of bisphosphonate. This study investigated the radiographic changes of mandibular cortical thickness upon bisphosphonate drug holiday. Materials and Methods: This retrospective study includes 36 patients diagnosed with MRONJ (medication-related osteonecrosis of the jaw) at Ajou University Dental Hospital in 2010-2021. All patients stopped taking bisphosphonate under consultation with the prescribing physicians. Panoramic radiographs were taken at the start of discontinuation (T0), 12 months after (T1), and 18 months after (T2) discontinuation of bisphosphonate, respectively. Mental index and panoramic mandibular index were calculated using Ledgerton's method. Paired t-tests were used to analyze differences over time. Results: The difference in indices (mental index and panoramic mandibular index) between T0 and T1 was not statistically significant (paired t-test, P>0.05). However, the difference in these indices between T1 and T2 was statistically significant (paired t-test, P<0.05). Conclusion: The cortical thickness of the mandible decreased in the late stage (after 18 months) as observed by panoramic radiograph.

C-Reactive Protein Signaling Pathways in Tumor Progression

  • Eun-Sook Kim;Sun Young Kim;Aree Moon
    • Biomolecules & Therapeutics
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    • v.31 no.5
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    • pp.473-483
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    • 2023
  • Many cancers arise from sites of chronic inflammation, which creates an inflammatory microenvironment surrounding the tumor. Inflammatory substances secreted by cells in the inflammatory environment can induce the proliferation and survival of cancer cells, thereby promoting cancer metastasis and angiogenesis. Therefore, it is important to identify the role of inflammatory factors in cancer progression. This review summarizes the signaling pathways and roles of C-reactive protein (CRP) in various cancer types, including breast, liver, renal, and pancreatic cancer, and the tumor microenvironment. Mounting evidence suggests the role of CRP in breast cancer, particularly in triple-negative breast cancer (TNBC), which is typically associated with a worse prognosis. Increased CRP in the inflammatory environment contributes to enhanced invasiveness and tumor formation in TNBC cells. CRP promotes endothelial cell formation and angiogenesis and contributes to the initiation and progression of atherosclerosis. In pancreatic and kidney cancers, CRP contributes to tumor progression. In liver cancer, CRP regulates inflammatory responses and lipid metabolism. CRP modulates the activity of various signaling molecules in macrophages and monocytes present in the tumor microenvironment, contributing to tumor development, the immune response, and inflammation. In the present review, we overviewed the role of CRP signaling pathways and the association between inflammation and cancer in various types of cancer. Identifying the interactions between CRP signaling pathways and other inflammatory mediators in cancer progression is crucial for understanding the complex relationship between inflammation and cancer.

FUMONISIN $B_1$IN DEVELOPING RATS ALTERS BRAIN SPHINGANINE LEVELS AND MYELINATTON.

  • Kwon, Oh-Seung;Schmued, Laurence. C.;William Slikker, JR
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 1996.12a
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    • pp.25-41
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    • 1996
  • KWON, O. S. SCHMUED, L. C. and LSIKKER, W. JR. Neurotoxiciligy. objectives of this study were to test the hypothesis that fumonisin $B_1$ ($FB_1$) alters sphinganine (Sa) levels and myelin synthesis in the central nervous system of developing rats. $FB_1$ (subcutaneous, 0. 4 or 0. 8 mg/kg/day) from postnatal days (PND) 3 to PND 12 resulted in a significantly increased in the brain of rats given 0. 8 mg $FB_1$/kg/day. To confirm the effect of limited nutrition on changes in the Sa levels and myelinogenesis, rats given 0.8mg $FB_1$/kg/day or treated by limited nutrition (temporary removal from dam during postnatal period) were compared to those in saline controls. Sa levels and Sa/So ratios were compared to those in saline in the 0.8 $FB_1$-treated, 3'-phosphohydrolase (CNP) activities were decreased significantly in both nutritionally limited and $FB_1$-exposed rats. These data indicate that sphingolipid metabolism in the central nervous system of develiping rats is vulnerable to $FB_1$ exposure. The hypomyelination associated with $FB_1$-treatment may be mediated by limited nutrition.

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Functional annotation of uncharacterized proteins from Fusobacterium nucleatum: identification of virulence factors

  • Kanchan Rauthan;Saranya Joshi;Lokesh Kumar;Divya Goel;Sudhir Kumar
    • Genomics & Informatics
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    • v.21 no.2
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    • pp.21.1-21.14
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    • 2023
  • Fusobacterium nucleatum is a gram-negative bacteria associated with diverse infections like appendicitis and colorectal cancer. It mainly attacks the epithelial cells in the oral cavity and throat of the infected individual. It has a single circular genome of 2.7 Mb. Many proteins in F. nucleatum genome are listed as "Uncharacterized." Annotation of these proteins is crucial for obtaining new facts about the pathogen and deciphering the gene regulation, functions, and pathways along with discovery of novel target proteins. In the light of new genomic information, an armoury of bioinformatic tools were used for predicting the physicochemical parameters, domain and motif search, pattern search, and localization of the uncharacterized proteins. The programs such as receiver operating characteristics determine the efficacy of the databases that have been employed for prediction of different parameters at 83.6%. Functions were successfully assigned to 46 uncharacterized proteins which included enzymes, transporter proteins, membrane proteins, binding proteins, etc. Apart from the function prediction, the proteins were also subjected to string analysis to reveal the interacting partners. The annotated proteins were also put through homology-based structure prediction and modeling using Swiss PDB and Phyre2 servers. Two probable virulent factors were also identified which could be investigated further for potential drug-related studies. The assigning of functions to uncharacterized proteins has shown that some of these proteins are important for cell survival inside the host and can act as effective drug targets.