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  • 1
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    Online Resource
    Chrysin Induces Apoptosis and Autophagy in Human Melanoma Cells via the mTOR/S6K Pathway
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 7 ( 2022-06-21), p. 1467-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 7 ( 2022-06-21), p. 1467-
    Abstract: Chrysin is known to exert anti-inflammatory, antioxidant, and anticancer effects. The aim of this study was to investigate the anticancer effects of chrysin in the human melanoma cells A375SM and A375P. The results obtained demonstrated successful inhibition of the viability of these cells by inducing apoptosis and autophagy. This was confirmed by the level of apoptosis-related proteins: Bax and cleaved poly (ADP-ribose) polymerase both increased, and Bcl-2 decreased. Moreover, levels of LC3 and Beclin 1, both autophagy-related proteins, increased in chrysin-treated cells. Autophagic vacuoles and acidic vesicular organelles were observed in both cell lines treated with chrysin. Both cell lines showed different tendencies during chrysin-induced autophagy inhibition, indicating that autophagy has different effects depending on the cell type. In A375SM, the early autophagy inhibitor 3-methyladenine (3-MA) was unaffected; however, cell viability decreased when treated with the late autophagy inhibitor hydroxychloroquine (HCQ). In contrast, HCQ was unaffected in A375P; however, cell viability increased when treated with 3-MA. Chrysin also decreased the phosphorylation of mTOR/S6K pathway proteins, indicating that this pathway is involved in chrysin-induced apoptosis and autophagy for A375SM and A375P. However, studies to elucidate the mechanisms of autophagy and the action of chrysin in vivo are still needed.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10071467
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 2
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    Online Resource
    Chrysin Induces Apoptosis via the MAPK Pathway and Regulates ERK/mTOR-Mediated Autophagy in MC-3 Cells
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 24 ( 2022-12-12), p. 15747-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 24 ( 2022-12-12), p. 15747-
    Abstract: Chrysin is a flavonoid found abundantly in substances, such as honey and phytochemicals, and is known to exhibit anticancer effects against various cancer cells. Nevertheless, the anticancer effect of chrysin against oral cancer has not yet been verified. Furthermore, the mechanism underlying autophagy is yet to be clearly elucidated. Thus, this study investigated chrysin-mediated apoptosis and autophagy in human mucoepidermoid carcinoma (MC-3) cells. The change in MC-3 cell viability was examined using a 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide cell viability assay, as well as 40,6-diamidino-2-phenylindole, annexin V, and propidium iodide staining. Western blotting was used to analyze the proteins related to apoptosis and the mitogen-activated protein kinase (MAPK) pathway. In addition, the presence or absence of autophagy and changes in the expression of related proteins were investigated using acridine orange staining and Western blot. The results suggested that chrysin induced apoptosis and autophagy in MC-3 oral cancer cells via the MAPK/extracellular signal-regulated kinase pathway. Moreover, the induced autophagy exerted a cytoprotective effect against apoptosis. Thus, the further reduced cell viability due to autophagy as well as apoptosis induction highlight therapeutic potential of chrysin for oral cancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232415747
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
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    Online Resource
    Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 18 ( 2023-09-11), p. 13949-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 18 ( 2023-09-11), p. 13949-
    Abstract: Currently, therapies for treating oral cancer have various side effects; therefore, research on treatment methods employing natural substances is being conducted. This study aimed to investigate piperine-induced apoptosis and autophagy in HSC-3 human oral cancer cells and their effects on tumor growth in vivo. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that piperine reduced the viability of HSC-3 cells and 4′,6-diamidino-2-phenylindole staining, annexin-V/propidium iodide staining, and analysis of apoptosis-related protein expression confirmed that piperine induces apoptosis in HSC-3 cells. Additionally, piperine-induced autophagy was confirmed by the observation of increased acidic vesicular organelles and autophagy marker proteins, demonstrating that autophagy in HSC-3 cells induces apoptosis. Mechanistically, piperine induced apoptosis and autophagy by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in HSC-3 cells. We also confirmed that piperine inhibits oral cancer tumor growth in vivo via antitumor effects related to apoptosis and PI3K signaling pathway inhibition. Therefore, we suggest that piperine can be considered a natural anticancer agent for human oral cancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241813949
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
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    Online Resource
    Piperlongumine Induces Apoptosis and Cytoprotective Autophagy via the MAPK Signaling Pathway in Human Oral Cancer Cells
    MDPI AG ; 2023
    In:  Biomedicines Vol. 11, No. 9 ( 2023-09-01), p. 2442-
    Details
    In: Biomedicines, MDPI AG, Vol. 11, No. 9 ( 2023-09-01), p. 2442-
    Abstract: Oral cancer is a malignant tumor that primarily affects areas such as the lips, tongue, buccal mucosa, salivary gland, and gingiva and has a very high malignancy. Piperlongumine (PL), isolated from long pepper (Piper longum L.), is a natural alkaloid with pharmacological effects, such as anti-inflammatory and anti-atherosclerotic effects. The effect and mechanism of PL in oral cancer cell lines has not been explored. Therefore, this study aimed to investigate the mechanism of anticancer effects of PL in the human oral cancer cell lines MC-3 and HSC-4 in vitro. This study demonstrated that PL inhibits cell proliferation by inducing apoptosis and autophagy in human oral cancer cell lines, which was confirmed by the levels of apoptosis- and autophagy-related proteins through Western blotting. Moreover, the pharmacological blockade of autophagy activation by hydroxychloroquine (HCQ), an autophagy inhibitor, significantly improved PL-induced apoptosis in MC-3 cells, suggesting a cytoprotective effect. In addition, activation of the mitogen-activated protein kinase (MAPK) signaling pathway contributed to PL-induced apoptosis. Collectively, the study suggested that combining an autophagy inhibitor with PL treatment can exert effective anticancer properties in oral cancer cells by inducing apoptosis and cytoprotective autophagy via the JNK-mediated MAPK pathway.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines11092442
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720867-9
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  • 5
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    Foaming with Starch: Exploring Faba Bean Aquafaba as a Green Alternative
    MDPI AG ; 2023
    In:  Foods Vol. 12, No. 18 ( 2023-09-11), p. 3391-
    Details
    In: Foods, MDPI AG, Vol. 12, No. 18 ( 2023-09-11), p. 3391-
    Abstract: The demand for sustainable and functional plant-based products is on the rise. Plant proteins and polysaccharides often provide emulsification and stabilization properties to food and food ingredients. Recently, chickpea cooking water, also known as aquafaba, has gained popularity as a substitute for egg whites in sauces, food foams, and baked goods due to its foaming and emulsifying capacities. This study presents a modified eco-friendly process to obtain process water from faba beans and isolate and characterize the foam-inducing components. The isolated material exhibits similar functional properties, such as foaming capacity, to aquafaba obtained by cooking pulses. To isolate the foam-inducing component, the faba bean process water was mixed with anhydrous ethanol, and a precipitated fraction was obtained. The precipitate was easily dissolved, and solutions prepared with the alcohol precipitate retained the foaming capacity of the original extract. Enzymatic treatment with α-amylase or protease resulted in reduced foaming capacity, indicating that both protein and carbohydrates contribute to the foaming capacity. The dried precipitate was found to be 23% protein (consisting of vicilin, α-legumin, and β-legumin) and 77% carbohydrate (amylose). Future investigations into the chemical structure of this foam-inducing agent can inform the development of foaming agents through synthetic or enzymatic routes. Overall, this study provides a potential alternative to aquafaba and highlights the importance of exploring plant-based sources for functional ingredients in the food industry.
    Type of Medium: Online Resource
    ISSN: 2304-8158
    URL: Article
    DOI: 10.3390/foods12183391
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704223-6
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  • 6
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    Nivolumab after Induction Chemotherapy in Previously Treated Non-Small-Cell Lung Cancer Patients with Low PD-L1 Expression
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 18 ( 2023-09-07), p. 4460-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 18 ( 2023-09-07), p. 4460-
    Abstract: This study aimed to investigate whether cyclophosphamide (C) and adriamycin (A) induction therapy (IT) prior to nivolumab could enhance the efficacy of nivolumab in previously treated patients with non-squamous (NSQ) non-small-cell lung cancer (NSCLC) with less than 10% programmed death-ligand 1 (PD-L1) expression. Twenty-two enrolled patients received four cycles of CA-IT every 3 weeks. Nivolumab was given 360 mg every 3 weeks from the second cycle and 480 mg every 4 weeks after four cycles of CA-IT. The median progression-free survival (PFS) and overall survival (OS) were 2.4 months and 11.6 months, respectively. Fluorescence-activated cell sorting revealed the lowest ratio of myeloid-derived suppressor cells (MDSCs) to CD8+T-cells in the responders. Proteomic analysis identified a consistent upregulation of extracellular matrix-receptor interactions and phagosome pathways in the responders. Among the differentially expressed proteins, the transferrin receptor protein (TFRC) was higher in the responders before treatment (fold change 〉 1.2). TFRC validation with an independent cohort showed the prognostic significance of either OS or PFS in patients with low PD-L1 expression. In summary, CA-IT did not improve nivolumab efficacy in NSQ-NSCLCs with low PD-L1 expression; however, it induced decreasing MDSC, resulting in a durable response. Higher baseline TFRC levels predicted a favorable response to nivolumab in NSCLC with low PD-L1 expression.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15184460
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 7
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    Assessing Health and Economic Benefits of Omega-3 Fatty Acid Supplementation on Cardiovascular Disease in the Republic of Korea
    MDPI AG ; 2023
    In:  Healthcare Vol. 11, No. 16 ( 2023-08-21), p. 2365-
    Details
    In: Healthcare, MDPI AG, Vol. 11, No. 16 ( 2023-08-21), p. 2365-
    Abstract: Background: Cardiovascular disease (CVD) is the primary cause of mortality worldwide and imposes a significant social burden on many countries. Methods: This study assessed the health and economic benefits of omega-3 associated with CVD. The meta-analysis estimated the risk ratio (RR) and absolute risk reduction (ARR), and the economic impact was calculated using direct and indirect costs related to CVD treatments in Korean adults. Results: A total of 33 studies were included in the meta-analysis on CVD outcomes, with 80,426 participants in the intervention group and 80,251 participants in the control group. The meta-analysis determined a significant reduction in omega-3 in CVD (RR = 0.92, 95% CI: 0.86~0.97) and ARR (1.48%). Additionally, the subgroup analysis indicated that higher doses and the long-term consumption of omega-3 could further enhance these effects. After applying ARR from meta-analysis to the target population of about 1,167,370 in 2021, the Republic of Korea, it was estimated that omega-3 consumption could result in an economic benefit of KRW 300 billion by subtracting the purchase expenses of omega-3 supplements from the total social cost savings. Conclusion: Omega-3 supplements can help to reduce the risk of CVD and subsequent economic benefits in the Republic of Korea.
    Type of Medium: Online Resource
    ISSN: 2227-9032
    URL: Article
    DOI: 10.3390/healthcare11162365
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2721009-1
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  • 8
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    Online Resource
    Development of a New Biomarker Model for Predicting Preterm Birth in Cervicovaginal Fluid
    MDPI AG ; 2022
    In:  Metabolites Vol. 12, No. 8 ( 2022-08-09), p. 734-
    Details
    In: Metabolites, MDPI AG, Vol. 12, No. 8 ( 2022-08-09), p. 734-
    Abstract: Preterm birth (PTB) is a social problem that adversely affects not only the survival rate of the fetus, but also the premature babies and families, so there is an urgent need to find accurate biomarkers. We noted that among causes, eubiosis of the vaginal microbial community to dysbiosis leads to changes in metabolite composition. In this study, short chain fatty acids (SCFAs) representing dysbiosis were derivatized using (N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide, MTBSTFA) and targeted analysis was conducted in extracted organic phases of cervicovaginal fluid (CVF). In residual aqueous CVF, polar metabolites produced biochemistry process were derivatized using methoxyamine and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA), and non-targeted analysis were conducted. Nine SCFAs were quantified, and 58 polar metabolites were detected in 90 clinical samples using gas chromatography/mass spectrometry (GC/MS). The criteria of statistical analysis and detection rate of clinical sample for development of PTB biomarkers were presented, and 19 biomarkers were selected based on it, consisting of 1 SCFA, 2 organic acids, 4 amine compounds, and 12 amino acids. In addition, the model was evaluated as a suitable indicator for predicting PTB without distinction between sample collection time. We hope that the developed biomarkers based on microbiota-derived metabolites could provide useful diagnostic biomarkers for actual patients and pre-pregnancy.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo12080734
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662251-8
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  • 9
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    Pulmonary Metastasizing Low-Grade Endometrial Stromal Sarcoma: Case Report and Review of Diagnostic Pitfalls
    MDPI AG ; 2022
    In:  Diagnostics Vol. 12, No. 2 ( 2022-01-21), p. 271-
    Details
    In: Diagnostics, MDPI AG, Vol. 12, No. 2 ( 2022-01-21), p. 271-
    Abstract: Pulmonary manifestations of benign metastasizing leiomyoma (BML) usually include multiple well-defined, round, bilateral nodules. Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine tumor. A 70-year-old woman visited the clinic complaining of acute cough and dyspnea in April 2017. Chest computed tomography (CT) revealed pneumothorax and multiple pulmonary nodules. She had a history of hysterectomy for uterine leiomyoma 23 years ago. Biopsy revealed that the pulmonary masses were consistent with BML. However, the patient had two subsequent episodes of acute, recurrent respiratory distress, accompanied by massive pleural effusions and hydropneumothorax over the next two years. A chest CT performed for acute dyspnea revealed large and multiple hydropneumothoraces. The size and distribution of pulmonary masses were aggravated along with cystic changes and bilateral pleural effusions. Given this aggressive feature, additional immunohistochemical findings and gynecologic pathologist review confirmed the correct diagnosis to be LG-ESS. After initiating anti-estrogen therapy, the patient achieved a partial response, without recurrence of symptoms, for 28 months. Metastatic LG-ESS responds well to anti-hormonal therapy. If the clinical pattern of a disease is different than expected, the possibility of a correction in the diagnosis should be considered.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics12020271
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662336-5
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  • 10
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    Early On-Treatment Prediction of the Mechanisms of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 6 ( 2022-03-15), p. 1512-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 6 ( 2022-03-15), p. 1512-
    Abstract: Background: Prediction of resistance mechanisms for epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) remains challenging. Thus, we investigated whether resistant cancer cells that expand shortly after EGFR-TKI treatment would eventually cause the resistant phenotype. Methods: We generated two EGFR-mutant lung cancer cell lines resistant to gefitinib (PC9GR and HCC827GR). The parent cell lines were exposed to short-term treatment with gefitinib or paclitaxel and then were assessed for EGFR T790M mutation and C-MET expression. These experiments were repeated in vivo and in clinically relevant patient-derived cell (PDC) models. For validation in clinical cases, we measured these gene alterations in plasma circulating tumor DNA (ctDNA) before and 8 weeks after starting EGFR-TKIs in four patients with EGFR-mutant lung cancer. Results: T790M mutation was only detected in the PC9GR cells, whereas C-MET amplification was detected in the HCC827GR cells. The T790M mutation level significantly increased in PC9 cells after short-term treatment with gefitinib but not in the paclitaxel. C-MET mRNA expression was only significantly increased in gefitinib-treated HCC827 cells. We confirmed that the C-MET copy number in HCC827 cells that survived after short-term gefitinib treatment was significantly higher than that in dead HCC827 cells. These findings were reproduced in the in vivo and PDC models. An early on-treatment increase in the plasma ctDNA level of these gene alterations was correlated with the corresponding resistance mechanism to EGFR-TKIs, a finding that was confirmed in post-treatment tumor tissues. Conclusions: Early on-treatment kinetics in resistance-related gene alterations may predict the final mechanism of EGFR-TKI resistance.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14061512
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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