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  • 1
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 11 ( 2023-05-24), p. 9171-
    Abstract: Through a comprehensive analysis of the gene expression and dependency in HCC patients and cell lines, LAT1 was identified as the top amino acid transporter candidate supporting HCC tumorigenesis. To assess the suitability of LAT1 as a HCC therapeutic target, we used CRISPR/Cas9 to knockout (KO) LAT1 in the epithelial HCC cell line, Huh7. Knockout of LAT1 diminished its branched chain amino acid (BCAA) transport activity and significantly reduced cell proliferation in Huh7. Consistent with in vitro studies, LAT1 ablation led to suppression of tumor growth in a xenograft model. To elucidate the mechanism underlying the observed inhibition of cell proliferation upon LAT1 KO, we performed RNA-sequencing analysis and investigated the changes in the mTORC1 signaling pathway. LAT1 ablation resulted in a notable reduction in phosphorylation of p70S6K, a downstream target of mTORC1, as well as its substrate S6RP. This reduced cell proliferation and mTORC1 activity were rescued when LAT1 was overexpressed. These findings imply an essential role of LAT1 for maintenance of tumor cell growth and additional therapeutic angles against liver cancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    In: Pharmaceuticals, MDPI AG, Vol. 16, No. 7 ( 2023-07-21), p. 1035-
    Abstract: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but severe adverse effect that can occur as a result of bisphosphonate treatment. This study aimed to examine the relationship between PPARγ and PPARGC1A polymorphisms and the BRONJ development in female osteoporosis patients undergoing bisphosphonate treatment. We prospectively conducted this nested case–control study at the Ewha Womans University Mokdong Hospital between 2014 and 2018. We assessed five single-nucleotide polymorphisms (SNPs) of PPARγ and six SNPs of PPARGC1A and performed a multivariable logistic regression analysis to determine the independent risk factors for developing BRONJ. There were a total of 123 patients included in this study and 56 patients (45.5%) developed BRONJ. In the univariate analysis, PPARGC1A rs2946385 and rs10020457 polymorphisms were significantly associated with BRONJ (p = 0.034, p = 0.020, respectively), although the results were not statistically significant in the multivariable analysis. Patients with the combined genotypes of GG in both PPARγ rs1151999 and PPARGC1A rs2946385 showed a 3.03-fold higher risk of BRONJ compared to individuals with other genotype combinations after adjusting for confounders (95% confidence interval (CI): 1.01–9.11). Old age (≥70 years) and duration of bisphosphonate use (≥60 months) increased the risk of BRONJ. The area under the receiver operating characteristic curve for the predicted probability was 0.78 (95% CI: 0.69–0.87, p 〈 0.001), demonstrating a satisfactory level of discriminatory power. Our study elucidated that PPARγ and PPARGC1A polymorphisms were interactively associated with BRONJ development. These results have potential implications for tailoring personalized treatments for females undergoing bisphosphonate therapy for osteoporosis.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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  • 3
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 6 ( 2021-06-10), p. 541-
    Abstract: Objective: This nested case–control study aimed to investigate the effects of VEGFA polymorphisms on the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in women with osteoporosis. Methods: Eleven single nucleotide polymorphisms (SNPs) of the VEGFA were assessed in a total of 125 patients. Logistic regression was performed for multivariable analysis. Machine learning algorithms, namely, fivefold cross-validated multivariate logistic regression, elastic net, random forest, and support vector machine, were developed to predict risk factors for BRONJ occurrence. Area under the receiver-operating curve (AUROC) analysis was conducted to assess clinical performance. Results: The VEGFA rs881858 was significantly associated with BRONJ development. The odds of BRONJ development were 6.45 times (95% CI, 1.69–24.65) higher among carriers of the wild-type rs881858 allele compared with variant homozygote carriers after adjusting for covariates. Additionally, variant homozygote (GG) carriers of rs10434 had higher odds than those with wild-type allele (OR, 3.16). Age ≥ 65 years (OR, 16.05) and bisphosphonate exposure ≥ 36 months (OR, 3.67) were also significant risk factors for BRONJ occurrence. AUROC values were higher than 0.78 for all machine learning methods employed in this study. Conclusion: Our study showed that the BRONJ occurrence was associated with VEGFA polymorphisms in osteoporotic women.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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  • 4
    In: Viruses, MDPI AG, Vol. 14, No. 5 ( 2022-05-19), p. 1093-
    Abstract: Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are disorders with similar clinical features; therefore, differentiating between them is difficult. We retrospectively collected data from 183 SFTS and 178 scrub typhus patients and validated an existing scoring system to develop a more sensitive, specific, and objective scoring system. We first applied the scoring systems proposed by Kim et al. to differentiate SFTS from scrub typhus. Multivariable logistic regression revealed that altered mental status, leukopenia, prolonged activated partial thromboplastin time (aPTT), and normal C-reactive protein (CRP) level (≤1.0 mg/dL) were significantly associated with SFTS. We changed the normal CRP level from ≤1.0 mg/dL to ≤3.0 mg/dL and replaced altered mental status with the creatine kinase (CK) level. The modified scoring system showed 97% sensitivity and 96% specificity for SFTS (area under the curve (AUC): 0.983) and a higher accuracy than the original scoring system (p = 0.0308). This study’s scoring system had 97% sensitivity and 98% specificity for SFTS (AUC: 0.992) and a higher accuracy than Kim et al.’s original scoring system (p = 0.0308). Our scoring system that incorporated leukopenia, prolonged aPTT, normal CRP level (≤3.0 mg/dL), and elevated CK level ( 〉 1000 IU/L) easily differentiated SFTS from scrub typhus in an endemic area.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2516098-9
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  • 5
    In: Viruses, MDPI AG, Vol. 14, No. 5 ( 2022-04-23), p. 881-
    Abstract: The clinical characteristics and the effect of viral RNA loads on fatality in 56 patients with severe fever with thrombocytopenia syndrome (SFTS) were analyzed. The non-survival group (12 patients) demonstrated a significantly higher mean age (77 years) than the survival group (44 patients, 65 years) (p = 0.003). The survival rates were 91.7% and 8.3% in patients with Ct values ≥30 and differed significantly (p = 0.001) in the survival and non-survival groups, respectively. The survival rates were 52.4% and 47.6% in patients with viral copy numbers ≥10,000 and 94.3% and 5.7% in patients with viral copy numbers 〈 10,000 in the survival and non-survival groups, respectively (p = 0.001). In a multivariate analysis, viral copy numbers and initial Acute Psychologic Assessment and Chronic Health Evaluation II (APACHE II) scores were identified as the factors affecting fatality (p = 0.015 and 0.011, respectively). SFTS viral RNA loads can be useful markers for the clinical prediction of mortality and survival.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2516098-9
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  • 6
    In: Plants, MDPI AG, Vol. 12, No. 11 ( 2023-05-30), p. 2175-
    Abstract: This study aimed to establish an efficient plant regeneration system from leaf-derived embryogenic structure cultures of Daphne genkwa. To induce embryogenic structures, fully expanded leaf explants of D. genkwa were cultured on Murashige and Skoog (MS) medium supplemented with 0, 0.1, 0.5, 1, 2, and 5 mg·L−1 2,4-dichlorophenoxyacetic acid (2,4-D), respectively. After 8 weeks of incubation, the highest frequency of embryogenic structure formation reached 100% when the leaf explants were cultivated on MS medium supplemented with 0.1 to 1 mg·L−1 2,4-D. At higher concentrations of 2,4-D (over 2 mg·L−1 2,4-D), the frequency of embryogenic structure formation significantly declined. Similar to 2,4-D, indole butyric acid (IBA) and α-naphthaleneacetic acid (NAA) treatments were also able to form embryogenic structures. However, the frequency of embryogenic structure formation was lower than that of 2,4-D. In particular, the yellow embryonic structure (YES) and white embryonic structure (WES) were simultaneously developed from the leaf explants of D. genkwa on culture medium containing 2,4-D, IBA, and NAA, respectively. Embryogenic calluses (ECs) were formed from the YES after subsequent rounds of subculture on MS medium supplemented with 1 mg·L−1 2,4-D. To regenerate whole plants, the embryogenic callus (EC) and the two embryogenic structures (YES and WES) were transferred onto MS medium supplemented with 0.1 mg·L−1 6-benzyl aminopurine (BA). The YES had the highest plant regeneration potential via somatic embryo and shoot development compared to the EC and WES. To our knowledge, this is the first successful report of a plant regeneration system via the somatic embryogenesis of D. genkwa. Thus, the embryogenic structures and plant regeneration system of D. genkwa could be applied to mass proliferation and genetic modification for pharmaceutical metabolite production in D. genkwa.
    Type of Medium: Online Resource
    ISSN: 2223-7747
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704341-1
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  • 7
    In: Biomedicines, MDPI AG, Vol. 11, No. 8 ( 2023-08-19), p. 2308-
    Abstract: Warfarin has a narrow therapeutic window and high intra- and inter-individual variability. Considering that many published papers on genotype-guided dosing are derived from European populations, the aim of this study was to investigate novel genetic variants associated with the variability of stable warfarin dose in the Korean population with cardiac valve replacement, using the GWAS approach. This retrospective cohort study was performed from January 1982 to December 2020 at the Severance Cardiovascular Hospital of Yonsei University College of Medicine. GWAS was performed to identify associations between genotypes and the warfarin maintenance dose, by comparing the allele frequency of genetic variants between individuals. Then, the extent of genetic and non-genetic factors on the dose variability was determined by multivariable regression analysis. The study enrolled 214 participants, and the most robust signal cluster was detected on chromosome 16 around VKORC1. Followed by VKORC1, three novel variants (NKX2-6 rs310279, FRAS1 rs4386623, and FAM201A rs1890109) showed an association with stable warfarin dose requirement in univariate analysis. The algorithm was constructed by using multivariable analysis that includes genetic and non-genetic factors, and it could explain 58.5% of the variations in stable warfarin doses. In this variability, VKORC1 rs9934438 and FRAS1 rs4386623 accounted for 33.0% and 9.9%, respectively. This GWAS analysis identified the fact that three novel variants (NKX2-6 rs310279, FRAS1 rs4386623, and FAM201A rs1890109) were associated with stable warfarin doses. Additional research is necessary to validate the results and establish personalized treatment strategies for the Korean population.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720867-9
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  • 8
    In: Plants, MDPI AG, Vol. 10, No. 8 ( 2021-08-09), p. 1635-
    Abstract: Weigela subsessilis is used in folk medicine to treat pain and allergic syndromes in Korea. However, the antibacterial and anti-inflammatory activities of W. subsessilis callus extract remain unexplored. In this study, we aimed to evaluate the W. subsessilis callus of pharmacological activity. Therefore, we first established in vitro calluses of W.subsessilis via plant tissue culture methods. We then evaluated the antioxidant and anti-inflammatory effects of W. subsessilis callus extract in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells. The W. subsessilis callus extract showed antioxidant and anti-inflammatory effects. These effects were regulated via suppression of mitogen-activated protein kinase signaling through LPS-induced translocation of nuclear factor kappa B (NF-κB) p65 from the cytoplasm to the nucleus. W. subsessilis callus extract also showed antibacterial and anti-inflammatory activities in Propionibacterium acnes-treated HaCaT keratinocyte cells. These results indicate that W. subsessilis callus extract has antioxidant, antibacterial and anti-inflammatory activities, suggesting its possible application in the treatment of inflammatory disorders.
    Type of Medium: Online Resource
    ISSN: 2223-7747
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2704341-1
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  • 9
    In: Plants, MDPI AG, Vol. 9, No. 12 ( 2020-12-03), p. 1701-
    Abstract: Toona sinensis has been traditionally used to treat dysentery, enteritis, flatulence, and itchiness. However, the existence of anti-inflammatory effects of T. sinensis on Propionibacterium acnes-induced skin disease is unknown. In vitro cultures of plant cells and tissues produced under controlled conditions offer a continuous production platform for plant natural products including pigments and anti-inflammatory agents. In this study, we determine the anti-inflammatory activities of an extract of in vitro grown adventitious shoots of T. sinensis on P. acnes, the etiologic agent of skin inflammation. The extract of T. sinensis showed antioxidant and anti-inflammatory activity in LPS-treated RAW264.7 cells. It also had antibacterial activity and anti-inflammatory effects on P. acnes-treated HaCaT cells. In addition, these effects were regulated by suppression of the mitogen-activated protein kinase (MAPK) pathways. These results suggesting the potential application of adventitious shoots of T. sinensis grown with an in vitro proliferation system as a medicine for treating P. acnes-induced inflammatory skin disease.
    Type of Medium: Online Resource
    ISSN: 2223-7747
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704341-1
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  • 10
    In: Foods, MDPI AG, Vol. 11, No. 16 ( 2022-08-17), p. 2477-
    Abstract: The Food and Agriculture Organization (FAO) has been estimating the potential of insects as human food since 2010, and for this reason, Tenebrio molitor larvae, also called mealworms, have been explored as an alternative protein source for various foods. In this study, in order to increase nutrient contents and improve preference as an alternative protein source, we fermented the T. molitor larvae by Cordyceps militaris mycelia. T. molitor larvae were prepared at optimal conditions for fermentation and fermented with C. militaris mycelia, and we analyzed T. molitor larvae change in functionality with proximate composition, β-glucan, cordycepin, adenosine, and free amino acids content. T. molitor larvae fermented by C. militaris mycelia showed higher total protein, total fiber, and β-glucan content than the unfermented larvae. In addition, the highest cordycepin content (13.75 mg/g) was observed in shaded dried T. molitor larvae fermented by C. militaris mycelia. Additionally, the isolated cordycepin from fermented T. molitor larvae showed similar cytotoxicity as standard cordycepin when treated with PC-9 cells. Therefore, we report that the optimized methods of T. molitor larvae fermented by C. militaris mycelia increase total protein, total fiber, β-glucan and produce the amount of cordycepin content, which can be contributed to healthy food and increase T. molitor larvae utilization.
    Type of Medium: Online Resource
    ISSN: 2304-8158
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704223-6
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