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  • 1
    Online Resource
    Online Resource
    Physicochemical, Pharmacokinetic, and Toxicity Evaluation of Methoxy Poly(ethylene glycol)-b-Poly(d,l-Lactide) Polymeric Micelles Encapsulating Alpinumisoflavone Extracted from Unripe Cudrania tricuspidata Fruit
    MDPI AG ; 2019
    In:  Pharmaceutics Vol. 11, No. 8 ( 2019-08-01), p. 366-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 11, No. 8 ( 2019-08-01), p. 366-
    Abstract: Alpinumisoflavone, a major compound in unripe Cudrania tricuspidata fruit is reported to exhibit numerous beneficial pharmacological activities, such as osteoprotective, antibacterial, estrogenic, anti-metastatic, atheroprotective, antioxidant, and anticancer effects. Despite its medicinal value, alpinumisoflavone is poorly soluble in water, which makes it difficult to formulate and administer intravenously (i.v.). To overcome these limitations, we used methoxy poly(ethylene glycol)-b-poly(d,l-lactide) (mPEG-b-PLA) polymeric micelles to solubilize alpinumisoflavone and increase its bioavailability, and evaluated their toxicity in vivo. Alpinumisoflavone-loaded polymeric micelles were prepared using thin-film hydration method, and their physicochemical properties were characterized for drug release, particle size, drug-loading (DL, %), and encapsulation efficiency (EE, %). The in vitro drug release profile was determined and the release rate of alpinumisoflavone from mPEG-b-PLA micelles was slower than that from drug solution, and sustained. Pharmacokinetic studies showed decreased total clearance and volume of distribution of alpinumisoflavone, whereas area under the curve (AUC) and bioavailability were significantly increased by incorporation in mPEG-b-PLA micelles. In vivo toxicity assay revealed that alpinumisoflavone-loaded mPEG-b-PLA micelles had no severe toxicity. In conclusion, we prepared an intravenous (i.v.) injectable alpinumisoflavone formulation, which was solubilized using mPEG-b-PLA micelles, and determined their physicochemical properties, pharmacokinetics, and toxicity profiles.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics11080366
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Toxicity of Proton Therapy versus Photon Therapy on Salvage Re-Irradiation for Non-Small Cell Lung Cancer
    MDPI AG ; 2022
    In:  Life Vol. 12, No. 2 ( 2022-02-16), p. 292-
    Details
    In: Life, MDPI AG, Vol. 12, No. 2 ( 2022-02-16), p. 292-
    Abstract: This study evaluated the toxicity associated with radiation techniques on curative re-irradiation (re-RT) in patients with thoracic recurrence of non-small cell lung cancer (NSCLC). From 2011 to 2019, we retrospectively reviewed the data of 63 patients with salvage re-RT for in-field or marginal recurrence of NSCLC at two independent institutions. Re-RT techniques using X-ray beams and proton beam therapy (PBT) were also included. Re-RT had a 2-year overall survival (OS) and local progression-free survival of 48.0% and 52.0%, respectively. Fifteen patients experienced grade 3 or higher toxicity after re-RT. The complication rates were 18.2% (4/22) and 26.8% (11/41) in PBT patients and X-ray patients, respectively. Airway or esophageal fistulas occurred in seven patients (11.1%). Fistulas or severe airway obstruction occurred in patients with tumors adjacent to the proximal bronchial tree and esophagus, who underwent hypofractionated radiotherapy (RT) or concurrent chemotherapy, and with a higher dose exposure to the esophagus. In conclusion, salvage re-RT was feasible even in patients with local recurrence within the previous RT field. PBT showed similar survival outcomes and toxicity to those of other techniques. However, thoracic re-RT should be performed carefully considering tumor location and RT regimens such as the fraction size and concurrent chemotherapy.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life12020292
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662250-6
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  • 3
    Online Resource
    Online Resource
    Histone Deacetylase Inhibitor, Trichostatin A, Synergistically Enhances Paclitaxel-Induced Cytotoxicity in Urothelial Carcinoma Cells by Suppressing the ERK Pathway
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 5 ( 2019-03-07), p. 1162-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 5 ( 2019-03-07), p. 1162-
    Abstract: Trichostatin A (TSA), an antifungal antibiotic derived from Streptomyces, inhibits mammalian histone deacetylases, and especially, selectively inhibits class I and II histone deacetylase (HDAC) families of enzymes. TSA reportedly elicits an antiproliferative response in multifarious tumors. This study investigated the antitumor effects of TSA alone and in combination with paclitaxel when applied to two high-grade urothelial carcinoma (UC) cell lines (BFTC-905 and BFTC-909). Fluorescence-activated cell sorting, flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay were used to assess TSA’s cytotoxicity and effects on apoptosis induction. TSA induced synergistic cytotoxicity, when combined with paclitaxel (combination index 〈 1), resulted in concomitant suppression of paclitaxel-induced activation of phospho-extracellular signal-regulated kinase (ERK) 1/2. A xenograft nude mouse model confirmed that TSA enhances the antitumor effects of paclitaxel. These findings demonstrate that the administration of TSA in combination with paclitaxel elicits a synergistic cytotoxic response. The results of this study indicate that the chemoresistance of UC could be circumvented by combining HDAC inhibitors to target the ERK pathway.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms20051162
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    The Inhibitory Effects and Cytotoxic Activities of the Stem Extract of Nepenthes miranda against Single-Stranded DNA-Binding Protein and Oral Carcinoma Cells
    MDPI AG ; 2023
    In:  Plants Vol. 12, No. 11 ( 2023-05-31), p. 2188-
    Details
    In: Plants, MDPI AG, Vol. 12, No. 11 ( 2023-05-31), p. 2188-
    Abstract: The carnivorous pitcher plants of the genus Nepenthes exhibit many ethnobotanical uses, including treatments of stomachache and fever. In this study, we prepared different extracts from the pitcher, stem, and leaf extracts of Nepenthes miranda obtained using 100% methanol and analyzed their inhibitory effects on recombinant single-stranded DNA-binding protein (SSB) from Klebsiella pneumoniae (KpSSB). SSB is essential for DNA replication and cell survival and thus an attractive target for potential antipathogen chemotherapy. Different extracts prepared from Sinningia bullata, a tuberous member of the flowering plant family Gesneriaceae, were also used to investigate anti-KpSSB properties. Among these extracts, the stem extract of N. miranda exhibited the highest anti-KpSSB activity with an IC50 value of 15.0 ± 1.8 μg/mL. The cytotoxic effects of the stem extract of N. miranda on the survival and apoptosis of the cancer cell lines Ca9-22 gingival carcinoma, CAL27 oral adenosquamous carcinoma, PC-9 pulmonary adenocarcinoma, B16F10 melanoma, and 4T1 mammary carcinoma cells were also demonstrated and compared. Based on collective data, the cytotoxic activities of the stem extract at a concentration of 20 μg/mL followed the order Ca9-22 〉 CAL27 〉 PC9 〉 4T1 〉 B16F10 cells. The stem extract of N. miranda at a concentration of 40 μg/mL completely inhibited Ca9-22 cell migration and proliferation. In addition, incubation with this extract at a concentration of 20 μg/mL boosted the distribution of the G2 phase from 7.9% to 29.2% in the Ca9-22 cells; in other words, the stem extract might suppress Ca9-22 cell proliferation by inducing G2 cell cycle arrest. Through gas chromatography–mass spectrometry, the 16 most abundant compounds in the stem extract of N. miranda were tentatively identified. The 10 most abundant compounds in the stem extract of N. miranda were used for docking analysis, and their docking scores were compared. The binding capacity of these compounds was in the order sitosterol 〉 hexadecanoic acid 〉 oleic acid 〉 plumbagin 〉 2-ethyl-3-methylnaphtho[2,3-b]thiophene-4,9-dione 〉 methyl α-d-galactopyranoside 〉 3-methoxycatechol 〉 catechol 〉 pyrogallol 〉 hydroxyhydroquinone; thus, sitosterol might exhibit the greatest inhibitory capacity against KpSSB among the selected compounds. Overall, these results may indicate the pharmacological potential of N. miranda for further therapeutic applications.
    Type of Medium: Online Resource
    ISSN: 2223-7747
    URL: Article
    DOI: 10.3390/plants12112188
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704341-1
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  • 5
    Online Resource
    Online Resource
    Could Natural Products Help in the Control of Obesity? Current Insights and Future Perspectives
    MDPI AG ; 2023
    In:  Molecules Vol. 28, No. 18 ( 2023-09-13), p. 6604-
    Details
    In: Molecules, MDPI AG, Vol. 28, No. 18 ( 2023-09-13), p. 6604-
    Abstract: Obesity is a global issue faced by many individuals worldwide. However, no drug has a pronounced effect with few side effects. Green tea, a well-known natural product, shows preventive effects against obesity by decreasing lipogenesis and increasing fat oxidation and antioxidant capacity. In contrast, other natural products are known to contribute to obesity. Relevant articles published on the therapeutic effect of natural products on obesity were retrieved from PubMed, Web of Science, and Scopus. The search was conducted by entering keywords such as “obesity”, “natural product”, and “clinical trial”. The natural products were classified as single compounds, foods, teas, fruits, herbal medicines—single extract, herbal medicines—decoction, and herbal medicines—external preparation. Then, the mechanisms of these medicines were organized into lipid metabolism, anti-inflammation, antioxidation, appetite loss, and thermogenesis. This review aimed to assess the efficacy and mechanisms of effective natural products in managing obesity. Several clinical studies reported that natural products showed antiobesity effects, including Coffea arabica (coffee), Camellia sinensis (green tea), Caulerpa racemosa (green algae), Allium sativum (garlic), combined Ephedra intermedia Schrenk, Thea sinensis L., and Atractylodes lancea DC extract (known as Gambisan), Ephedra sinica Stapf, Angelica Gigantis Radix, Atractylodis Rhizoma Alba, Coicis semen, Cinnamomi cortex, Paeoniae radix alba, and Glycyrrhiza uralensis (known as Euiiyin-tang formula). Further studies are expected to refine the pharmacological effects of natural products for clinical use.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules28186604
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2008644-1
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  • 6
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    Pancreatic β-Cell O-GlcNAc Transferase Overexpression Increases Susceptibility to Metabolic Stressors in Female Mice
    MDPI AG ; 2021
    In:  Cells Vol. 10, No. 10 ( 2021-10-19), p. 2801-
    Details
    In: Cells, MDPI AG, Vol. 10, No. 10 ( 2021-10-19), p. 2801-
    Abstract: The nutrient-sensor O-GlcNAc transferase (Ogt), the sole enzyme that adds an O-GlcNAc-modification onto proteins, plays a critical role for pancreatic β-cell survival and insulin secretion. We hypothesized that β-cell Ogt overexpression would confer protection from β-cell failure in response to metabolic stressors, such as high-fat diet (HFD) and streptozocin (STZ). Here, we generated a β-cell-specific Ogt in overexpressing (βOgtOE) mice, where a significant increase in Ogt protein level and O-GlcNAc-modification of proteins were observed in islets under a normal chow diet. We uncovered that βOgtOE mice show normal peripheral insulin sensitivity and glucose tolerance with a regular chow diet. However, when challenged with an HFD, only female βOgtOE (homozygous) Hz mice developed a mild glucose intolerance, despite increased insulin secretion and normal β-cell mass. While female mice are normally resistant to low-dose STZ treatments, the βOgtOE Hz mice developed hyperglycemia and glucose intolerance post-STZ treatment. Transcriptome analysis between islets with loss or gain of Ogt by RNA sequencing shows common altered pathways involving pro-survival Erk and Akt and inflammatory regulators IL1β and NFkβ. Together, these data show a possible gene dosage effect of Ogt and the importance O-GlcNAc cycling in β-cell survival and function to regulate glucose homeostasis.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells10102801
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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