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1.
J Environ Manage ; 366: 121831, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39018862

ABSTRACT

Climate change and intensified human activities are exacerbating the frequency and severity of extreme precipitation events, necessitating more precise and timely flood risk assessments. Traditional models often fail to dynamically and accurately assess flood risks due to their static nature and limited handling of spatiotemporal variations. This study confronts these challenges head-on by developing a novel coupled hydrological-hydrodynamic model integrated with a Block-wise use of the TOPMODEL (BTOP) and the Rainfall-Runoff-Inundation (RRI) model. This integrated approach enables the rapid acquisition of high-precision flood inundation simulation results across large-scale basins, addressing a significant gap in dynamic flood risk assessment and zoning. A critical original achievement of this research lies in developing and implementing a comprehensive vertical-horizontal combined weighting method that incorporates spatiotemporal information for dynamic evaluation indicators, significantly enhancing the accuracy and rationality of flood risk assessments. This innovative method successfully addresses the challenges posed by objective and subjective weighting methods, presenting a balanced and robust framework for flood risk evaluation. The findings from the Min River Basin in China, as a case study, demonstrate the effectiveness of the BTOP-RRI model in capturing the complex variations in runoff and the detailed simulations of flood processes. The model accurately identifies the timing of these peaks, offering insights into the dynamic evolution of flood risks and providing a more precise and timely assessment tool for policymakers and disaster management authorities. The flood risk assessment results demonstrate good consistency with the actual regional conditions. In particular, high-risk areas exhibit distinct characteristics along the river channel, with the distribution area significantly increasing with a sudden surge in runoff. Intense precipitation events expand areas classified as moderate and high risk, gradually shrinking as precipitation levels decrease. This study significantly advances flood risk assessment methodologies by integrating cutting-edge modeling techniques with comprehensive weighting strategies. This is essential for improving the scientific foundation and decision-making processes in regional flood control efforts.

2.
Pharm Biol ; 61(1): 918-926, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37323017

ABSTRACT

CONTEXT: Lucialdehyde B (LB), an effective triterpenoid isolated from Ganoderma lucidum (Leyss. ex Fr.) Karst. (Polyproraceae), exerts cytotoxic activity against nasopharyngeal carcinoma CNE2 cells. OBJECTIVE: To investigate the antiproliferative and pro-apoptotic effects of LB on CNE2 cells and explore its underlying mechanisms. MATERIALS AND METHODS: LB concentrations of 5-40 µg/mL were used. Cell proliferation was determined using MTT, CFSE, and colony formation assays. LB-induced apoptosis and cell cycle arrest were measured by flow cytometry after 48-h LB treatments. Fluorescence microscopy and flow cytometry were performed to measure the alteration of MMP, mPTP opening, ROS level, and Ca2+ content in CNE2 cells. Western blotting was performed to evaluate the expression of mitochondrial apoptosis-related and Ras/ERK signaling proteins. RESULTS: IC50 values of LB against CNE2 cells for 24, 48, and 72 h were 25.42 ± 0.87, 14.83 ± 0.93, and 11.60 ± 0.77 µg/mL, respectively. The CFSE assay showed that the cell proliferation index was 12.70 in the LB treatment group and 31.44 in the control group. LB significantly reduced clonogenic capacity, promoted cell apoptosis and induced cell cycle arrest at the G2/M phase. Our observations also revealed that LB induced ROS and calcium aggregation, opening of mPTP, MMP reduction, upregulation of mitochondrial apoptosis-related protein expression and inhibition of Ras/ERK signaling cascades. DISCUSSION: LB suppresses proliferation and induces mitochondrial-dependent apoptosis in nasopharyngeal carcinoma CNE2 cells. CONCLUSIONS: LB may have a potential use as a clinical drug candidate for nasopharyngeal carcinoma treatment.


Subject(s)
Nasopharyngeal Neoplasms , Triterpenes , Humans , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/pathology , Reactive Oxygen Species , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Apoptosis , Triterpenes/pharmacology , Cell Proliferation , Cell Line, Tumor
3.
Nat Prod Res ; 34(21): 3094-3100, 2020 Nov.
Article in English | MEDLINE | ID: mdl-31230492

ABSTRACT

A new demethyl abietane diterpenoid, Triptotin K (3) together with three known compounds, friedelin (1), canophyllal (2), and triptonoterpene (4) were isolated from the roots of Tripterygium wilfordii Hook. f. by silica gel column and preparative high performance liquid chromatography. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Triptotin K showed cytotoxic activities against KB, KBv200, HepG2, and MCF-7/ADM cells lines with IC50 values of 29.88, 36.50, 39.55, and 41.38 µM, respectively.


Subject(s)
Abietanes/chemistry , Abietanes/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Tripterygium/chemistry , Abietanes/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Drug Screening Assays, Antitumor , Hep G2 Cells , Humans , MCF-7 Cells , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Roots/chemistry , Triterpenes/isolation & purification , Triterpenes/pharmacology
4.
Anticancer Agents Med Chem ; 20(2): 237-244, 2020.
Article in English | MEDLINE | ID: mdl-31749435

ABSTRACT

BACKGROUND: Ganoderma lucidum (Leyss. ex Fr.) Karst. (G. lucidum, GL) belongs to the family of Ganodermataceae (Basidiomycetes), and possesses activities including antitumor, antimicrobial, antiviral, and antiaging activities. Triterpenoids are typical chemical constituents in G. lucidum, and play an important role in the anti-cancer effects. According to the substituent group at the carbon 26 position, GL total triterpenes fraction can be divided into two types, Neutral Triterpene Fraction (NTF) and an Acidic Triterpene Fraction (ATF). The anti-cancer effects of total triterpenes fraction and total acidic triterpene fraction extracted from G. lucidum have been widely known in vivo and in vitro, whereas few have focused on total neutral triterpene fraction. OBJECTIVE: The aim of this study was to evaluate the anti-cancer effects of NTF extracted from G. lucidum in vitro and in vivo and explore its anti-cancer active constituents on SW620 human colorectal cancer cells. METHODS: NTF and ATF were extracted from the dry fruiting body of G. lucidum by impregnation method with 90% ethanol, and further isolated by using alkaline extraction and acid precipitation method. The total triterpenoid content of NTF and ATF was determined by using ultraviolet-visible spectrophotometry. The cytotoxic effects on human colon cancer cells SW480, SW620, SW1116, and mouse embryonic fibroblast cell line NIH3T3 were evaluated by using the MTT method. The anti-cancer activity of NTF in vivo was evaluated in Athymic nude mice against SW620 cells. An activity-guided separation and purification process were used to identify the anti-cancer active constituents of NTF by column and preparative high-performance liquid chromatography. Structures of the constituents were confirmed by 1H-NMR, 13C-NMR and MS. Protein expression was performed by Western blotting. RESULTS: The percentage of total triterpenoids was 46.7% and 57.6% in ATF and NTF, respectively. Both fractions could reduce the viability of SW480, SW620, and SW1116 cells in vitro, whereby NTF exhibited a stronger effect than ATF. NTF markedly inhibited the growth of SW620 cell xenografts in mice at doses (250, 500mg/kg) during the treatment. Furthermore, a new garnoderic alcohol, named as ethyl ganoderate A and eight known ganoderic alcohols were isolated and identified from NTF by a bioassay-guided separation process. All of these compounds possessed anti-cancer activities against SW620 cells in vitro. As a representative ganoderma alcohol, ganodermanondiol significantly reduced the viability of SW620 cells through the induction of apoptosis, which was associated with the upregulated the levels of cleaved-poly (ADP-ribose) polymerase (PARP), cleaved-caspase-3, and -9. In addition, ganodermanondiol showed low cytotoxic activity against normal NIH3T3 cells. CONCLUSION: NTF are potential anti-cancer agents against colon cancer and the active constituents may be ganoderic alcohols whose inhibitory mechanism of anti-cancer action may be related to the activation of a mitochondrial- dependent pathway.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cell Survival/drug effects , Ganoderma/chemistry , Triterpenes/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Cell Line, Tumor , Colorectal Neoplasms , Fibroblasts/drug effects , Humans , Mice , Mice, Nude , Neoplasms, Experimental/drug therapy , Phytotherapy , Triterpenes/chemistry
5.
Nat Prod Res ; 33(5): 732-735, 2019 Mar.
Article in English | MEDLINE | ID: mdl-29130339

ABSTRACT

Multidrug resistance is a major unresolved obstacle to successful cancer chemotherapy. It is often associated with an elevated efflux of a variety of anticancer drugs by ATP-binding cassette transporters including P-glycoprotein, BCRP and MRP1. In this study, the reversal effect of Ethyl lucidenates A on K562/A02 cells was investigated. At concentrations of 10 µM, Ethyl lucidenates A could reverse the resistance of K562/A02 to vincristine up to 7.59 folds. Mechanistically, Ethyl lucidenates A could increase the intracellular accumulation of vincristine in K562/A02 cells through inhibiting the P-glycoprotein mediated drug-transport activity by rhodamine accumulation assay and cell cycle analysis. Further mechanistic investigation found that Ethyl lucidenates A did not alter P-glycoprotein expression. In conclusion, Ethyl lucidenates A could reverse the multidrug resistance of K562/A02 cells via its influence on P-glycoprotein drug-transport activity and thus, be a potential multidrug resistance reversal agent.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Lanosterol/analogs & derivatives , Vincristine/pharmacology , ATP Binding Cassette Transporter, Subfamily B/metabolism , Doxorubicin/pharmacology , Humans , K562 Cells , Lanosterol/pharmacology , Reishi/chemistry
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