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  • 1
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    Online Resource
    Pyrimethamine Modulates Interplay between Apoptosis and Autophagy in Chronic Myelogenous Leukemia Cells
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 15 ( 2021-07-29), p. 8147-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 15 ( 2021-07-29), p. 8147-
    Abstract: Pyrimethamine (Pyri) is being used in combination with other medications to treat serious parasitic infections of the body, brain, or eye and to also reduce toxoplasmosis infection in the patients with HIV infection. Additionally, Pyri can display significant anti-cancer potential in different tumor models, but the possible mode of its actions remains unclear. Hence, in this study, the possible anti-tumoral impact of Pyri on human chronic myeloid leukemia (CML) was deciphered. Pyri inhibited cell growth in various types of tumor cells and exhibited a marked inhibitory action on CML cells. In addition to apoptosis, Pyri also triggered sustained autophagy. Targeted inhibition of autophagy sensitized the tumor cells to Pyri-induced apoptotic cell death. Moreover, the activation of signal transducer and activator of transcription 5 (STAT5) and its downstream target gene Bcl-2 was attenuated by Pyri. Accordingly, small interfering RNA (siRNA)-mediated STAT5 knockdown augmented Pyri-induced autophagy and apoptosis and promoted the suppressive action of Pyri on cell viability. Moreover, ectopic overexpression of Bcl-2 protected the cells from Pyri-mediated autophagy and apoptosis. Overall, the data indicated that the attenuation of STAT5-Bcl-2 cascade by Pyri can regulate its growth inhibitory properties by simultaneously targeting both apoptosis and autophagy cell death mechanism(s).
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22158147
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 2
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    2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway
    MDPI AG ; 2017
    In:  Molecules Vol. 22, No. 7 ( 2017-07-11), p. 1157-
    Details
    In: Molecules, MDPI AG, Vol. 22, No. 7 ( 2017-07-11), p. 1157-
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules22071157
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2008644-1
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  • 3
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    The Knockdown of TREK-1 in Hippocampal Neurons Attenuate Lipopolysaccharide-Induced Depressive-Like Behavior in Mice
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 23 ( 2019-11-24), p. 5902-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 23 ( 2019-11-24), p. 5902-
    Abstract: TWIK-related potassium channel-1 (TREK-1) is broadly expressed in the brain and involved in diverse brain diseases, such as seizures, ischemia, and depression. However, the cell type-specific roles of TREK-1 in the brain are largely unknown. Here, we generated a Cre-dependent TREK-1 knockdown (Cd-TREK-1 KD) transgenic mouse containing a gene cassette for Cre-dependent TREK-1 short hairpin ribonucleic acid to regulate the cell type-specific TREK-1 expression. We confirmed the knockdown of TREK-1 by injecting adeno-associated virus (AAV) expressing Cre into the hippocampus of the mice. To study the role of hippocampal neuronal TREK-1 in a lipopolysaccharide (LPS)-induced depression model, we injected AAV-hSyn-BFP (nCTL group) or AAV-hSyn-BFP-Cre (nCre group) virus into the hippocampus of Cd-TREK-1 KD mice. Interestingly, the immobility in the tail suspension test after LPS treatment did not change in the nCre group. Additionally, some neurotrophic factors (BDNF, VEGF, and IGF-1) significantly increased more in the nCre group compared to the nCTL group after LPS treatment, but there was no difference in the expression of their receptors. Therefore, our data suggest that TREK-1 in the hippocampal neurons has antidepressant effects, and that Cd-TREK-1 KD mice are a valuable tool to reveal the cell type-specific roles of TREK-1 in the brain.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms20235902
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
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  • 4
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    Transcriptional Profiles of Secondary Metabolite Biosynthesis Genes and Cytochromes in the Leaves of Four Papaver Species
    MDPI AG ; 2018
    In:  Data Vol. 3, No. 4 ( 2018-11-28), p. 55-
    Details
    In: Data, MDPI AG, Vol. 3, No. 4 ( 2018-11-28), p. 55-
    Abstract: Poppies are well-known plants in the family Papaveraceae that are rich in alkaloids. This family contains 61 species, and in this study we sequenced the transcriptomes of four species’ (Papaver rhoeas, Papaver nudicaule, Papaver fauriei, and Papaver somniferum) leaves. These transcripts were systematically assessed for the expression of secondary metabolite biosynthesis (SMB) genes and cytochromes, and their expression profiles were assessed for use in bioinformatics analyses. This study contributed 265 Gb (13 libraries with three biological replicates) of leaf transcriptome data from three Papaver plant developmental stages. Sequenced transcripts were assembled into 815 Mb of contigs, including 226 Mb of full-length transcripts. The transcripts for 53 KEGG pathways, 55 cytochrome superfamilies, and benzylisoquinoline alkaloid biosynthesis (BIA) were identified and compared to four other alkaloid-rich genomes. Additionally, 22 different alkaloids and their relative expression profiles in three developmental stages of Papaver species were assessed by targeted metabolomics using LC-QTOF-MS/MS. Collectively, the results are given in co-occurrence heat-maps to help researchers obtain an overview of the transcripts and their differential expression in the Papaver development life cycle, particularly in leaves. Moreover, this dataset will be a valuable resource to derive hypotheses to mitigate an array of Papaver developmental and secondary metabolite biosynthesis issues in the future.
    Type of Medium: Online Resource
    ISSN: 2306-5729
    URL: Article
    DOI: 10.3390/data3040055
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2856531-9
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  • 5
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    Antioxidant and Anti-Inflammatory Activities of High-Glucosinolate-Synthesis Lines of Brassica rapa
    MDPI AG ; 2023
    In:  Antioxidants Vol. 12, No. 9 ( 2023-08-30), p. 1693-
    Details
    In: Antioxidants, MDPI AG, Vol. 12, No. 9 ( 2023-08-30), p. 1693-
    Abstract: Excessive oxidative stress and inflammatory responses are associated with the development of various diseases, including cancer. Glucosinolates (GSLs) are phytochemicals known for their antioxidant properties, and doubled haploid lines (DHLs) of Brassica rapa with high GSL contents (HGSL) were intentionally developed from two edible subspecies of Brassica rapa: B. rapa subsp. trilocularis and B. rapa subsp. chinensis. The purpose of the present study is to assess the capacity of HGSL DHLs to mitigate oxidative stress and inflammation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, compared to pak choi as a parental control. Our findings demonstrate that HGSL DH lines effectively suppressed the expression of inducible nitric oxide synthase, leading to the reduced levels of nitric oxide at non-toxic concentrations. Additionally, these lines exhibited scavenging activity against reactive oxygen species and free radicals. The enhanced antioxidant capacity of HGSL DHLs was mechanistically attributed to the upregulation of antioxidant enzymes, such as NADPH quinone oxidoreductase 1 (NQO1), the glutamate–cysteine ligase catalytic subunit (GCLC), and heme oxygenase-1 (HMOX1). Furthermore, we confirmed that these effects were mediated through the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway via p38 phosphorylation. Moreover, HGSL DHLs demonstrated inhibitory effects on pro-inflammatory cytokines and signal transducers and activators of transcription 3 (STAT3) phosphorylation. Collectively, our results indicate that HGSL DHLs possess better antioxidant and anti-inflammatory properties compared to the parental control pak choi in LPS-stimulated RAW264.7 cells, suggesting that HGSL DHLs of Brassica rapa could be considered as a beneficial daily vegetable for reducing the risk of inflammation-associated diseases.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox12091693
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 6
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    Anticancer Effects of High Glucosinolate Synthesis Lines of Brassica rapa on Colorectal Cancer Cells
    MDPI AG ; 2022
    In:  Antioxidants Vol. 11, No. 12 ( 2022-12-14), p. 2463-
    Details
    In: Antioxidants, MDPI AG, Vol. 11, No. 12 ( 2022-12-14), p. 2463-
    Abstract: Chemoprevention is a method of health control in modern industrialized societies. Traditional breeding (hybridization) has been widely used to produce new (sub)species with beneficial phenotypes. Previously, we produced a number of doubled haploid (DH) lines of Brassica rapa with a high glucosinolate (GSL) content. In this study, we evaluated the anticancer activities of extracts from three selected high-GSL (HGSL)-containing DH lines (DHLs) of Brassica rapa in human colorectal cancer (CRC) cells. The three HGSL DHL extracts showed anti-proliferative activities in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay and pro-apoptotic activities in the cell cycle or annexin V analysis with the induction of pro-apoptotic protein expression in CRC cells. Mechanistically, HGSL DHL extracts inhibited the NF-κB and ERK pathways, leading to a reduction in the nuclear localization of NF-κB p65. In addition, reactive oxygen species were induced by HGSL DHL extract treatment in CRC cells. In conclusion, our data suggest that the newly developed HGSL DHLs possess enhanced anticancer activities and are potentially helpful as a daily vegetable supplement with chemopreventive activities.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox11122463
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 7
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    Non-Renal Risk Factors for Chronic Kidney Disease in Liver Recipients with Functionally Intact Kidneys at 1 Month
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 14 ( 2022-07-20), p. 4203-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 14 ( 2022-07-20), p. 4203-
    Abstract: Chronic kidney disease (CKD) is a critical complication of liver transplants, of which non-renal risk factors are not fully understood yet. This study aimed to reveal pre- and post-transplant risk factors for CKD ( 〈 60 mL/min/1.73 m2), examining liver recipients with functionally intact kidneys one month after grafting using nationwide cohort data. Baseline risk factors were analyzed with multivariable Cox regression analyses and post-transplant risk factors were investigated with the time-dependent Cox model and matched analyses of time-conditional propensity scores. Of the 2274 recipients with a one-month eGFR ≥ 60 mL/min/1.73 m2, 494 (22.3%) developed CKD during a mean follow-up of 36.6 ± 14.4 months. Age, female sex, lower body mass index, pre-transplant diabetes mellitus, and lower performance status emerged as baseline risk factors for CKD. Time-dependent Cox analyses revealed that recurrent hepatocellular carcinoma (HR = 1.93, 95% CI 1.06–3.53) and infection (HR = 1.44, 95% CI 1.12–1.60) were significant post-transplant risk factors for CKD. Patients who experienced one of those factors showed a significantly higher risk of subsequent CKD compared with the matched controls who lacked these features (p = 0.013 for recurrent hepatocellular carcinoma, and p = 0.003 for infection, respectively). This study clarifies pre- and post-transplant non-renal risk factors, which lead to renal impairment after LT independently from patients’ renal functional reserve.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11144203
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 8
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    Hypoxia Promotes Angiogenic Effect in Extracranial Arteriovenous Malformation Endothelial Cells
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 16 ( 2022-08-14), p. 9109-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 16 ( 2022-08-14), p. 9109-
    Abstract: Arteriovenous malformation (AVM) is characterized by high-flow blood vessels connecting arteries and veins without capillaries. This disease shows increased angiogenesis and a pathophysiological hypoxic environment in proximal tissues. Here, we analyzed the effects of hypoxia on angiogenesis in the endothelial cells (ECs) of AVM and normal tissues. ECs from human normal and AVM tissues were evaluated using immunocytochemistry with CD31. In vitro tube formation under hypoxia was tested in both ECs using Matrigel. The relative expression of angiogenesis-related genes was measured using real-time PCR. Under normoxia, CD31 was significantly higher in AVM ECs (79.23 ± 0.65%) than in normal ECs (74.15 ± 0.70%). Similar results were observed under hypoxia in AVM ECs (63.85 ± 1.84%) and normal ECs (60.52 ± 0.51%). In the tube formation test under normoxic and hypoxic conditions, the junction count and total vessel length were significantly greater in AVM ECs than normal ECs. Under both normoxia and hypoxia, the angiogenesis-related gene FSTL1 showed a significantly higher expression in AVM ECs than in normal ECs. Under hypoxia, CSPG4 expression was significantly lower in AVM ECs than in normal ECs. Accordingly, the angiogenic effect was increased in AVM ECs compared with that in normal ECs. These results provide a basic knowledge for an AVM treatment strategy.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23169109
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 9
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    Increased Risk of Chronic Periodontitis in Chronic Rhinosinusitis Patients: A Longitudinal Follow-Up Study Using a National Health-Screening Cohort
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 4 ( 2020-04-19), p. 1170-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 4 ( 2020-04-19), p. 1170-
    Abstract: This study compared the risk of chronic periodontitis (CP) between chronic rhinosinusitis (CRS) and non-chronic rhinosinusitis (control) patients using a national cohort dataset from the Korean Health Insurance Review and Assessment Service. CRS (n = 5951) and control participants (n = 23,804) were selected after 1:4 ratio matching for age, sex, income, region of residence, and preoperative CP visits. Postoperative CP visits were measured between 2002 and 2015. The margin of equivalence of the difference between the CRS and control groups was set between −0.5 and 0.5. Statistical significance was noted in the post-index date (ID) of the third, fourth, and fifth year periods. In subgroup analyses according to age and sex, statistical significance was observed in 40–59-year-old males in post-ID third, fourth, and fifth year periods, ≥60-year-old males in post-ID third and fourth year periods, and ≥60-year-old females in post-ID fifth year period (p 〈 0.05, each). In another subgroup analysis based on the number of pre-ID CP visits, statistical significance was observed for pre-ID CP (0 time) in the third, fourth, and fifth year periods (p 〈 0.05, each). This study revealed that CRS participants were likely to receive CP diagnosis and treatment.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9041170
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 10
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    Causal Effect of Chondroitin, Glucosamine, Vitamin, and Mineral Intake on Kidney Function: A Mendelian Randomization Study
    MDPI AG ; 2023
    In:  Nutrients Vol. 15, No. 15 ( 2023-07-26), p. 3318-
    Details
    In: Nutrients, MDPI AG, Vol. 15, No. 15 ( 2023-07-26), p. 3318-
    Abstract: The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from a genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse-variance weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = −0.113%, standard error (SE) = 0.03%, p-value = 2 × 10−4; glucosamine, eGFR change beta = −0.240%, SE = 0.035%, p-value = 6 × 10−12). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426%, SE = 0.136%, p-value = 1 × 10−25). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu15153318
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518386-2
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