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  1. Article ; Online: Regulation of base excision repair during adipogenesis and osteogenesis of bone marrow-derived mesenchymal stem cells.

    Kim, Min / Jang, Hyun-Jin / Baek, Song-Yi / Choi, Kyung-Jin / Han, Dong-Hee / Sung, Jung-Suk

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 16384

    Abstract: Bone marrow-derived human mesenchymal stem cells (hMSCs) can differentiate into various lineages, such as chondrocytes, adipocytes, osteoblasts, and neuronal lineages. It has been shown that the high-efficiency DNA-repair capacity of hMSCs is decreased ... ...

    Abstract Bone marrow-derived human mesenchymal stem cells (hMSCs) can differentiate into various lineages, such as chondrocytes, adipocytes, osteoblasts, and neuronal lineages. It has been shown that the high-efficiency DNA-repair capacity of hMSCs is decreased during their differentiation. However, the underlying its mechanism during adipogenesis and osteogenesis is unknown. Herein, we investigated how alkyl-damage repair is modulated during adipogenic and osteogenic differentiation, especially focusing on the base excision repair (BER) pathway. Response to an alkylation agent was assessed via quantification of the double-strand break (DSB) foci and activities of BER-related enzymes during differentiation in hMSCs. Adipocytes showed high resistance against methyl methanesulfonate (MMS)-induced alkyl damage, whereas osteoblasts were more sensitive than hMSCs. During the differentiation, activities, and protein levels of uracil-DNA glycosylase were found to be regulated. In addition, ligation-related proteins, such as X-ray repair cross-complementing protein 1 (XRCC1) and DNA polymerase β, were upregulated in adipocytes, whereas their levels and recruitment declined during osteogenesis. These modulations of BER enzyme activity during differentiation influenced DNA repair efficiency and the accumulation of DSBs as repair intermediates in the nucleus. Taken together, we suggest that BER enzymatic activity is regulated in adipogenic and osteogenic differentiation and these alterations in the BER pathway led to different responses to alkyl damage from those in hMSCs.
    MeSH term(s) Humans ; Adipogenesis/genetics ; Osteogenesis/physiology ; Bone Marrow/metabolism ; Cells, Cultured ; Cell Differentiation/physiology ; DNA Repair ; Mesenchymal Stem Cells ; X-ray Repair Cross Complementing Protein 1/metabolism
    Chemical Substances XRCC1 protein, human ; X-ray Repair Cross Complementing Protein 1
    Language English
    Publishing date 2023-09-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-43737-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Belvarafenib penetrates the BBB and shows potent antitumor activity in a murine melanoma brain metastasis model.

    Kim, Yu-Yon / Park, Hyunjin / Song, Taehun / Choi, Kyungjin / Dolton, Michael / Mao, Jialin / Kim, Jisook / Ahn, Young Gil / Suh, Kwee Hyun / Kim, Young Hoon

    Clinical & experimental metastasis

    2023  Volume 40, Issue 2, Page(s) 137–148

    Abstract: Brain metastasis is a common complication in melanoma patients with BRAF and NRAS mutations and has a poor prognosis. Although BRAF inhibitors are clinically approved, their poor brain penetration limits their efficacy in brain metastasis. Thus, melanoma ...

    Abstract Brain metastasis is a common complication in melanoma patients with BRAF and NRAS mutations and has a poor prognosis. Although BRAF inhibitors are clinically approved, their poor brain penetration limits their efficacy in brain metastasis. Thus, melanoma brain metastasis still requires better treatment. Belvarafenib, a pan-RAF inhibitor, has reported antitumor activity in melanoma with RAF and RAS mutations in animal models and patients. However, brain permeability and antitumor efficacy on brain metastasis have not been determined. This study confirmed the brain penetration of belvarafenib, the antitumor activity on BRAF and NRAS mutant melanoma, and the efficacy on melanoma within the brain. Belvarafenib strongly suppressed melanoma in BRAF V600E mutant A375SM tumor-bearing mice. It also significantly inhibited tumor growth in NRAS mutant SK-MEL-30 and K1735 tumor-bearing mice and synergized to enhance the antitumor activity combined with cobimetinib or atezolizumab. Belvarafenib was penetrated at considerable levels into the brains of mice and rats following oral administration. The exposure of belvarafenib in the brain was similar to or higher than that in plasma, and this high brain penetration differed significantly from that of other BRAF inhibitors with low brain penetration. Most importantly, belvarafenib strongly reduced tumor burden and markedly improved survival benefits in mice intracranially implanted with A375SM melanoma. These results demonstrated that belvarafenib, which has favorable BBB permeability, and potent antitumor activity on the tumors with BRAF/NRAS mutations, may be a promising therapeutic option for patients with BRAF/NRAS mutant melanoma brain metastasis.
    MeSH term(s) Mice ; Rats ; Animals ; Proto-Oncogene Proteins B-raf/genetics ; Melanoma/drug therapy ; Melanoma/genetics ; Melanoma/pathology ; Protein Kinase Inhibitors/therapeutic use ; Brain Neoplasms/drug therapy ; Mutation ; Cell Line, Tumor ; Skin Neoplasms/pathology
    Chemical Substances Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Protein Kinase Inhibitors
    Language English
    Publishing date 2023-02-10
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 604952-7
    ISSN 1573-7276 ; 0262-0898
    ISSN (online) 1573-7276
    ISSN 0262-0898
    DOI 10.1007/s10585-023-10198-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Leaf Condition of Rice (Oryza sativa L.) in Response to Cold Stress during Ripening Stage

    Hwang, Woon-Ha / Lee, Chung-Gun / Jeong, Jae-Heok / Lee, Hyen-Seok / Choi, Kyung-Jin

    Journal of crop science and biotechnology. 2019 Dec., v. 22, no. 5

    2019  

    Abstract: Cold stress can decrease yield and quality of rice. Although many studies have investigated the impact of cold stress on rice, researches on physiological changes of rice plants under low temperature during ripening stage are insufficient. Thus, the ... ...

    Abstract Cold stress can decrease yield and quality of rice. Although many studies have investigated the impact of cold stress on rice, researches on physiological changes of rice plants under low temperature during ripening stage are insufficient. Thus, the objective of this study was to analyze changes of leaf condition in rice plant during ripening stage in response to low temperature. Results showed that photosynthesis activity of flag leaf was decreased continuously after heading and that it was reduced more in cold condition. Chlorophyll content in flag leaf was also reduced in control and cold conditions after heading. In control condition, chlorophyll content showed a significant correlation with nitrogen content in leaf. However, chlorophyll content under cold condition showed a high correlation with Malondialdehyde content. These results strongly suggest that the leaf lipid peroxidation by cold stress can induce the decrease of leaf chlorophyll content and photosynthesis activity during ripening stage in rice.
    Keywords Oryza sativa ; chlorophyll ; cold ; cold stress ; heading ; leaf chlorophyll content ; leaves ; lipid peroxidation ; malondialdehyde ; nitrogen content ; photosynthesis ; rice ; ripening ; temperature
    Language English
    Dates of publication 2019-12
    Size p. 489-494.
    Publishing place The Korean Society of Crop Science
    Document type Article
    ZDB-ID 2300030-2
    ISSN 2005-8276 ; 1975-9479
    ISSN (online) 2005-8276
    ISSN 1975-9479
    DOI 10.1007/s12892-019-0292-0
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis.

    Kim, Ju-Young / Lim, Dong-Mee / Park, Hyung-Seo / Moon, Chan-Il / Choi, Kyung-Jin / Lee, Seong-Kyu / Baik, Haing-Woon / Park, Keun-Young / Kim, Byung-Joon

    Journal of pharmacological sciences

    2019  Volume 118, Issue 1, Page(s) 65–74

    Abstract: Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from β-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by β-cell ... ...

    Abstract Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from β-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by β-cell exhaustion and apoptosis. ER stress induced by Ca
    Language English
    Publishing date 2019-06-11
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2104264-0
    ISSN 1347-8648 ; 1347-8613
    ISSN (online) 1347-8648
    ISSN 1347-8613
    DOI 10.1254/jphs.11072FP
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Synthesis and evaluation of thieno[3,2-d]pyrimidine derivatives as novel FMS inhibitors.

    Kim, Yu-Yon / Choi, Jaeyul / Choi, Kyungjin / Park, Changhee / Kim, Young Hoon / Suh, Kwee Hyun / Ham, Young Jin / Jang, Sun Young / Lee, Kyu-Hang / Hwang, Kwang Woo

    Bioorganic & medicinal chemistry letters

    2018  Volume 29, Issue 2, Page(s) 271–275

    Abstract: Colony stimulating factor-1 receptor (CSF-1R or FMS) and it ligand, CSF-1, signaling regulates the differentiation and function of tumor-associated macrophages (TAMs) that play an important role in tumor progression. Derivatives of thieno[3,2-d] ... ...

    Abstract Colony stimulating factor-1 receptor (CSF-1R or FMS) and it ligand, CSF-1, signaling regulates the differentiation and function of tumor-associated macrophages (TAMs) that play an important role in tumor progression. Derivatives of thieno[3,2-d]pyrimidine were synthesized and evaluated as kinase inhibitors of FMS. The most representative compound 21 showed strong activity (IC
    MeSH term(s) Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Female ; Humans ; Ligands ; Molecular Structure ; Protein Kinase Inhibitors/chemical synthesis ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; Pyrimidines/chemical synthesis ; Pyrimidines/chemistry ; Pyrimidines/pharmacology ; Receptor, Macrophage Colony-Stimulating Factor/antagonists & inhibitors ; Receptor, Macrophage Colony-Stimulating Factor/metabolism ; Structure-Activity Relationship
    Chemical Substances Antineoplastic Agents ; Ligands ; Protein Kinase Inhibitors ; Pyrimidines ; thieno(2,3-d)pyrimidine ; Receptor, Macrophage Colony-Stimulating Factor (EC 2.7.10.1)
    Language English
    Publishing date 2018-11-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2018.11.037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Anatomical reconstruction of the spring ligament using peroneus longus tendon graft.

    Choi, Kyungjin / Lee, Samuel / Otis, James C / Deland, Jonathan T

    Foot & ankle international

    2003  Volume 24, Issue 5, Page(s) 430–436

    Abstract: Posterior tibial tendon insufficiency is often associated with failure of the spring ligament and flatfoot deformity. Arch correction procedures involving bony realignment, such as lateral column lengthening or joint fusions, can predispose to arthritis. ...

    Abstract Posterior tibial tendon insufficiency is often associated with failure of the spring ligament and flatfoot deformity. Arch correction procedures involving bony realignment, such as lateral column lengthening or joint fusions, can predispose to arthritis. Soft tissue reconstruction may provide a more anatomical correction without these complications. The purpose of this investigation was to compare the ability of three different spring ligament reconstruction procedures to correct flatfoot deformity. A deformity model of 5 degrees - 15 degrees talonavicular abduction was created in 10 cadaver foot-ankle specimens. Three reconstructions utilizing the peroneus longus tendon were evaluated for their ability to correct talonavicular abduction and subtalar eversion under 357 N vertical GRF load. A superomedial/plantar passage of the tendon through the calcaneus and navicular was shown to be more effective than either of the other two approaches, correcting the talonavicular joint from 9.1 degrees +/- 8.1 degrees abducted to 1.0 degree +/- 6.8 degrees adducted, and the subtalar joint from 3.1 degrees +/- 3.3 degrees everted to 0.4 degrees +/- 4.2 degrees inverted. Thus, an anatomical reconstruction of a model of a failed spring ligament was demonstrated to be effective in the correction of a flatfoot deformity produced in cadaver foot-ankle specimens.
    MeSH term(s) Biomechanical Phenomena ; Cadaver ; Flatfoot/etiology ; Flatfoot/surgery ; Foot ; Foot Bones/surgery ; Foot Deformities, Acquired/surgery ; Humans ; Ligaments/surgery ; Models, Biological ; Posterior Tibial Tendon Dysfunction/complications ; Random Allocation ; Tendons/surgery
    Language English
    Publishing date 2003-05
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 1183283-6
    ISSN 1944-7876 ; 1071-1007
    ISSN (online) 1944-7876
    ISSN 1071-1007
    DOI 10.1177/107110070302400510
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Exendin-4 protects against sulfonylurea-induced β-cell apoptosis.

    Kim, Ju-Young / Lim, Dong-Mee / Park, Hyung-Seo / Moon, Chan-Il / Choi, Kyung-Jin / Lee, Seong-Kyu / Baik, Haing-Woon / Park, Keun-Young / Kim, Byung-Joon

    Journal of pharmacological sciences

    2011  Volume 118, Issue 1, Page(s) 65–74

    Abstract: Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from β-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by β-cell ... ...

    Abstract Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from β-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by β-cell exhaustion and apoptosis. ER stress induced by Ca(2+) depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear. Glucagon like peptide-1 (GLP-1) has anti-apoptotic effects in β-cells after the induction of oxidative and ER stress. In this study, we examined the anti-apoptotic action of a GLP-1 analogue in β-cell lines and islets against ER stress induced by chronic treatment of sulfonylurea. HIT-T15 and dispersed islet cells were exposed to glibenclamide for 48 h, and apoptosis was evaluated using Annexin/PI flow cytometry. Expression of the ER stress-related molecules and sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 2/3 was determined by real-time PCR and western blot analysis. Chronic exposure to glibenclamide increased apoptosis by depletion of ER Ca(2+) concentration through reduced expression of SERCA 2/3. Pretreatment with Exendin-4 had an anti-apoptotic role through ER stress modulation and ER Ca(2+) replenishing by SERCA restoration. These findings will further the understanding of one cause of glibenclamide-induced β-cell loss and therapeutic availability of GLP-1-based drugs in secondary failure by sulfonylurea during treatment of diabetes.
    MeSH term(s) Animals ; Apoptosis/drug effects ; Calcium/metabolism ; Cell Line ; Cricetinae ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress/drug effects ; Exenatide ; Glucagon-Like Peptide 1/agonists ; Glyburide/adverse effects ; Hypoglycemic Agents/adverse effects ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Peptides/pharmacology ; Rats ; Rats, Sprague-Dawley ; Venoms/pharmacology
    Chemical Substances Hypoglycemic Agents ; Peptides ; Venoms ; Glucagon-Like Peptide 1 (89750-14-1) ; Exenatide (9P1872D4OL) ; Glyburide (SX6K58TVWC) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2011-12-21
    Publishing country Japan
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2104264-0
    ISSN 1347-8648 ; 1347-8613
    ISSN (online) 1347-8648
    ISSN 1347-8613
    DOI 10.1254/jphs.11072fp
    Database MEDical Literature Analysis and Retrieval System OnLINE

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