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1.
Plant Biotechnol J ; 22(7): 1981-1988, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38425137

RESUMO

Succulents, valued for their drought tolerance and ornamental appeal, are important in the floriculture market. However, only a handful of succulent species can be genetically transformed, making it difficult to improve these plants through genetic engineering. In this study, we adapted the recently developed cut-dip-budding (CDB) gene delivery system to transform three previously recalcitrant succulent varieties - the dicotyledonous Kalanchoe blossfeldiana and Crassula arborescens and the monocotyledonous Sansevieria trifasciata. Capitalizing on the robust ability of cut leaves to regenerate shoots, these plants were successfully transformed by directly infecting cut leaf segments with the Agrobacterium rhizogenes strain K599. The transformation efficiencies were approximately 74%, 5% and 3.9%-7.8%, respectively, for K. blossfeldiana and C. arborescens and S. trifasciata. Using this modified CDB method to deliver the CRISPR/Cas9 construct, gene editing efficiency in K. blossfeldiana at the PDS locus was approximately 70%. Our findings suggest that succulents with shoot regeneration ability from cut leaves can be genetically transformed using the CDB method, thus opening up an avenue for genetic engineering of these plants.


Assuntos
Agrobacterium , Edição de Genes , Plantas Geneticamente Modificadas , Transformação Genética , Edição de Genes/métodos , Agrobacterium/genética , Plantas Geneticamente Modificadas/genética , Sistemas CRISPR-Cas/genética , Folhas de Planta/genética , Kalanchoe/genética , Técnicas de Transferência de Genes
2.
Environ Geochem Health ; 46(1): 14, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38147177

RESUMO

Arsenic contamination in the groundwater occurs in various parts of the world due to anthropogenic and natural sources, adversely affecting human health and ecosystems. The current study intends to examine the groundwater hydrogeochemistry containing elevated arsenic (As), predict As levels in groundwater, and determine the aptness of groundwater for drinking in the Vehari district, Pakistan. Four hundred groundwater samples from the study region were collected for physiochemical analysis. As levels in groundwater samples ranged from 0.1 to 52 µg/L, with an average of 11.64 µg/L, (43.5%), groundwater samples exceeded the WHO 2022 recommended limit of 10 µg/L for drinking purposes. Ion-exchange processes and the adsorption of ions significantly impacted the concentration of As. The HCO3- and Na+ are the dominant ions in the study area, and the water types of samples were CaHCO3, mixed CaMgCl, and CaCl, demonstrating that rock-water contact significantly impacts hydrochemical behavior. The geochemical modeling indicated negative saturation indices with calcium carbonate and other salt minerals, encompassing aragonite, calcite, dolomite, and halite. The dissolution mechanism suggested that these minerals might have implications for the mobilization of As in groundwater. A combination of human-induced and natural sources of contamination was unveiled through principal component analysis (PCA). Artificial neural networks (ANN), random forest (RF), and logistic regression (LR) were used to predict As in the groundwater. The data have been divided into two parts for statistical analysis: 20% for testing and 80% for training. The most significant input variables for As prediction was determined using Chi-squared analysis. The receiver operating characteristic area under the curve and confusion matrix were used to evaluate the models; the RF, ANN, and LR accuracies were 0.89, 0.85, and 0.76. The permutation feature and mean decrease in impurity determine ten parameters that influence groundwater arsenic in the study region, including F-, Fe2+, K+, Mg2+, Ca2+, Cl-, SO42-, NO3-, HCO3-, and Na+. The present study shows RF is the best model for predicting groundwater As contamination in the research area. The water quality index showed that 161 samples represent poor water, and 121 samples are unsuitable for drinking. Establishing effective strategies and regulatory measures is imperative in Vehari to ensure the sustainability of groundwater resources.


Assuntos
Arsênio , Água Subterrânea , Humanos , Modelos Logísticos , Paquistão , Algoritmo Florestas Aleatórias , Ecossistema , Redes Neurais de Computação , Íons
3.
Cell Commun Signal ; 20(1): 200, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36575468

RESUMO

BACKGROUND: Despite advances in treatment, patients with refractory colorectal cancer (CRC) still have poor long-term survival, so there is a need for more effective therapeutic options. METHODS: To evaluate the HDAC8 inhibition efficacy as a CRC treatment, we examined the effects of various HDAC8 inhibitors (HDAC8i), including BMX (NBM-T-L-BMX-OS01) in combination with temozolomide (TMZ) or other standard CRC drugs on p53 mutated HT29 cells, as well as wild-type p53 HCT116 and RKO cells. RESULTS: We showed that HDAC8i with TMZ cotreatment resulted in HT29 arrest in the S and G2/M phase, whereas HCT116 and RKO arrest in the G0/G1 phase was accompanied by high sub-G1. Subsequently, this combination approach upregulated p53-mediated MGMT inhibition, leading to apoptosis. Furthermore, we observed the cotreatment also enabled triggering of cell senescence and decreased expression of stem cell biomarkers. Mechanistically, we found down-expression levels of ß-catenin, cyclin D1 and c-Myc via GSK3ß/ß-catenin signaling. Intriguingly, autophagy also contributes to cell death under the opposite status of ß-catenin/p62 axis, suggesting that there exists a negative feedback regulation between Wnt/ß-catenin and autophagy. Consistently, the Gene Set Enrichment Analysis (GSEA) indicated both apoptotic and autophagy biomarkers in HT29 and RKO were upregulated after treating with BMX. CONCLUSIONS: BMX may act as a HDAC8 eraser and in combination with reframed-TMZ generates a remarkable synergic effect, providing a novel therapeutic target for various CRCs. Video Abstract.


Assuntos
Apoptose , Neoplasias Colorretais , Inibidores de Histona Desacetilases , Temozolomida , Humanos , beta Catenina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/metabolismo , Proteínas Repressoras/metabolismo , Temozolomida/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Via de Sinalização Wnt , Inibidores de Histona Desacetilases/farmacologia , Células HT29
4.
Bioorg Chem ; 107: 104395, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33384144

RESUMO

We report the design, synthesis, and biological evaluation of 13 new and 1 known anthraquinone derivatives which exerted cytotoxicity against PC3, A549 and NTUB1 cell lines. The results indicate that, among these 14, compounds-1 and 14 showed the highest growth inhibitory effect on NTUB1 and PC3 cells, respectively. Compound-1 at lower doses targets DNA, induces DNA damage and subsequently triggers G2/M arrest and apoptotic cell death at 24 h. Previously we reported that 14 induced PC3 cell autophagy and in treated PC3 cells, cleaved caspase-3 and cleaved PARP, and survivin did not increase and increase, respectively. The autophagic and necrotic cell deaths mediated by 14-triggered ROS generation. Our study is the first to investigate the biological mechanism of 14 action in detail. We find that when 14 was co-administrated with Bafilomycin A1 (BAF) in PC3 cells, rapid necrotic cell death occurred with no cleaved caspase-3 and cleaved PARP activation and increasing the expression of survivin. We further show that necrotic signaling in these cells coincided with production of reactive oxygen species. In the present study, we developed methods to synthesize five new 14 analogues for studing the structure-activity relationships. This study could provide valuable sight to find new antitumor agents for cancer therapy.


Assuntos
Antraquinonas/farmacologia , Antineoplásicos/farmacologia , Antraquinonas/síntese química , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
5.
Hepatology ; 68(1): 141-154, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29328502

RESUMO

Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy preferentially recruits and degrades the oncogenic microRNA (miR)-224 to prevent HCC. Therefore, in the present study, we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development. We found that increased autophagic activity leads to cyclin D1 ubiquitination and selective recruitment to the autophagosome (AP) mediated by a specific receptor, sequestosome 1 (SQSTM1), followed by fusion with lysosome and degradation. Autophagy-selective degradation of ubiquitinated cyclin D1 through SQSTM1 was confirmed using cyclin D1/ubiquitin binding site (K33-238 R) and phosphorylation site (T286A) mutants, lentivirus-mediated silencing autophagy-related 5 (ATG5), autophagy-related 7 (ATG7), and Sqstm1 knockout cells. Functional studies revealed that autophagy-selective degradation of cyclin D1 plays suppressive roles in cell proliferation, colony, and liver tumor formation. Notably, an increase of autophagic activity by pharmacological inducers (amiodarone and rapamycin) significantly suppressed tumor growth in both the orthotopic liver tumor and subcutaneous tumor xenograft models. Our findings provide evidence of the underlying mechanism involved in the regulation of cyclin D1 by selective autophagy to prevent tumor formation. CONCLUSION: Taken together, our data demonstrate that autophagic degradation machinery and the cell-cycle regulator, cyclin D1, are linked to HCC tumorigenesis. We believe these findings may be of value in the development of alternative therapeutics for HCC patients. (Hepatology 2018;68:141-154).


Assuntos
Autofagia , Carcinoma Hepatocelular/metabolismo , Ciclina D1/metabolismo , Neoplasias Hepáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Autofagossomos/metabolismo , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Camundongos SCID , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Proteína Sequestossoma-1/metabolismo , Taiwan/epidemiologia , Ubiquitinação
6.
Int J Mol Sci ; 20(3)2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30678307

RESUMO

Thioridazine (THD) is a common phenothiazine antipsychotic drug reported to suppress growth in several types of cancer cells. We previously showed that THD acts as an antiglioblastoma and anticancer stem-like cell agent. However, the signaling pathway underlying autophagy and apoptosis induction remains unclear. THD treatment significantly induced autophagy with upregulated AMPK activity and engendered cell death with increased sub-G1 in glioblastoma multiform (GBM) cell lines. Notably, through whole gene expression screening with THD treatment, frizzled (Fzd) proteins, a family of G-protein-coupled receptors, were found, suggesting the participation of Wnt/ß-catenin signaling. After THD treatment, Fzd-1 and GSK3ß-S9 phosphorylation (inactivated form) was reduced to promote ß-catenin degradation, which attenuated P62 inhibition. The autophagy marker LC3-II markedly increased when P62 was released from ß-catenin inhibition. Additionally, the P62-dependent caspase-8 activation that induced P53-independent apoptosis was confirmed by inhibiting T-cell factor/ß-catenin and autophagy flux. Moreover, treatment with THD combined with temozolomide (TMZ) engendered increased LC3-II expression and caspase-3 activity, indicating promising drug synergism. In conclusion, THD induces autophagy in GBM cells by not only upregulating AMPK activity, but also enhancing P62-mediated autophagy and apoptosis through Wnt/ß-catenin signaling. Therefore, THD is a potential alternative therapeutic agent for drug repositioning in GBM.


Assuntos
Autofagia/efeitos dos fármacos , Cateninas/metabolismo , Glioma/metabolismo , Tioridazina/farmacologia , Apoptose/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Western Blotting , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
7.
J Cell Physiol ; 233(1): 497-505, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28294332

RESUMO

The tautomeric pair of garcinielliptone FC (GFC) is a novel tautomeric pair of polyprenyl benzophenonoid isolated from the pericarps of Garcinia subelliptica Merr. (G. subelliptica, Clusiaceae), a tree with abundant sources of polyphenols. Our previous report demonstrated that GFC induced apoptosis on various types of human cancer cell lines including chemoresistant human colorectal cancer HT-29 cells. In the present study, we observed that many autophagy-related genes in GFC-treated HT-29 cells were up- and down-regulated using a cDNA microarray containing oncogenes and kinase genes. GFC-induced autophagy of HT-29 cells was confirmed by observing the formation of acidic vesicular organelles, LC3 puncta, and double-membrane autophagic vesicles using flow cytometry, confocal microscopy, and transmission electron microscopy, respectively. Inhibition of AKT/mTOR/P70S6K signaling as well as formation of Atg5-Atg12 and PI3K/Beclin-1 complexes were observed using Western blot. Administration of autophagy inhibitor (3-methyladenine and shRNA Atg5) and apoptosis inhibitor Z-VAD showed that the GFC-induced autophagy was cytotoxic form and GFC-induced apoptosis enhanced GFC-induced autophagy. Our data suggest the involvement of autophagy and apoptosis in GFC-induced anticancer mechanisms of human colorectal cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Proteína 12 Relacionada à Autofagia/genética , Proteína 12 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/ultraestrutura , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Transfecção
8.
Ecotoxicol Environ Saf ; 150: 251-259, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29288906

RESUMO

In this paper, the adsorption behaviors of Cu(II) from the aqueous solution using rape straw powders were studied. The effects of initial Cu(II) concentration, pH range and absorbent dosage on the adsorption efficiency of Cu(II) by rape straw powder were investigated by Box-Behnken Design based on response surface methodology. The values of coefficient constant of the nonlinear models were 0.9997, 0.9984 and 0.9944 for removal Cu(II) from aqueous solution using rape straw shell, seed pods and straw pith core, respectively, which could navigate the design space for various factors on effects of biosorption Cu(II) from aqueous solution. The various factors of pH and biosorbents dosage were the key factors that affecting the removal efficiency of Cu(II) from aqueous solution. The biosorption equilibrium data presented its favorable monolayer adsorption Cu(II) onto shell, seed pods and straw pith core, respectively. The pseudo-second order kinetic model was the proper approach to determine the adsorption kinetics. The biosorption of Cu(II) onto surfaces of rape straw powders were confirmed and ion-exchanged in the adsorption process by energy dispersive spectrometer. The critical groups, -OH, -CH, -NH3+, -CH3, -NH and -C-O, exhibited by the infrared spectra results, changed to suggest that these groups played critical roles, especially -CH3 in the adsorption of copper ions onto rape straw powders. The study provided evidences that rape straw powders can be used for removing Cu(II) from aqueous water.


Assuntos
Brassica/química , Cobre/análise , Modelos Teóricos , Poluentes Químicos da Água/análise , Adsorção , Concentração de Íons de Hidrogênio , Íons , Cinética , Pós , Soluções , Propriedades de Superfície
9.
Environ Monit Assess ; 190(7): 391, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29892786

RESUMO

This study used a total of 474 groundwater samples analyzed from 2014 data to evaluate the distribution of groundwater quality in the Water and Sanitation Agency (WASA) jurisdiction of Lahore city, Pakistan. The study further assessed the variations in suitability of groundwater for drinking (emphasis on arsenic and fluoride) and irrigation using spatial correlation technique in GIS. The hydrochemical analysis revealed a predominance of Mg-Ca-HCO3-SO4 and Ca-Mg-HCO3-SO4 type. Distribution analysis indicated relatively higher salinity (TDSmax = 1667 mg/L), total hardness (THmax = 558 mg/L), and alkalinity (HCO3-max = 584 mg/L) in the south-eastern region of the city, while the central part displayed the highest levels of SO4 and NO3. Also, the eastern region (north-south) of Lahore had significantly elevated As concentrations (up to 86 µg/L). The order of exceedance in terms of arsenic was Gunj Bakhsh town (17.4%), Nishter town (16.4%), Iqbal town (9.8%), Aziz Batti and Shalimar town (8.1%), and Ravi town (3%). The groundwater was classified as average saline to highly saline, except few samples in Aziz Batti/Shalimar town that were in non-saline group. Otherwise, the various indices classified the groundwater for irrigation as generally acceptable. With the various irrigation quality indices displaying discernible variations for the entire study area, it was observed from the distribution maps that the groundwater suitability for irrigation is relatively excellent in the areas away from industries and landfill locations. Also, the chloride analysis shows 98.7% of the groundwater samples belong to the very fresh and fresh water class. Thus, continued monitoring and studying the changes in groundwater quality in Lahore is imperative.


Assuntos
Água Potável/análise , Monitoramento Ambiental/métodos , Água Subterrânea/análise , Poluentes Químicos da Água/análise , Abastecimento de Água , Irrigação Agrícola/métodos , Arsênio/análise , Água Potável/química , Fluoretos/análise , Água Doce/análise , Água Subterrânea/química , Paquistão , Fosfatos , Salinidade , Análise Espacial , Qualidade da Água/normas
10.
Apoptosis ; 22(10): 1235-1245, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28741092

RESUMO

To fight cancer at its roots by targeting cancer stem cells is a promising approach for therapy. Previously, an indolylquinoline derivative, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), was reported effectively inhibiting the growth of lung cancer cells through impairment of cellular mitochondria functions. To address more on drug efficiency, the study further exploited if EMMQ can impede the propagation of tumorspheres stemmed from non-small cell lung cancer cells. EMMQ inhibited proliferation of spheroids in culture. In animal models, administration of the drug attenuated the spheroid tumorigenicity. The activated apoptosis alleviated growth of xenograft tumors in immune-deficient mice as established by the enriched tumorspheres. More evidence suggested that the reduced stemness of the spheroid tumors is attributed to apoptotic death. The findings supported that EMMQ is an eligible approach to eradicate the minor but tumorigenic lung cancer tumorspheres.


Assuntos
Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Indóis/farmacologia , Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Transplante de Neoplasias , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/transplante , Ensaio Tumoral de Célula-Tronco
11.
J Cell Physiol ; 230(4): 930-46, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25216025

RESUMO

Our previous reports showed that justicidin A (JA), a novel and pure arylnaphthalide lignan isolated from Justicia procumbens, induces apoptosis of human colorectal cancer cells and hepatocellular carcinoma cells, leading to the suppression of both tumor cell growth in NOD-SCID mice. Here, we reveal that JA induces autophagy in human colorectal cancer HT-29 cells by conversion of autophagic marker LC3-I to LC3-II. Furthermore, LC3 puncta and autophagic vesicle formation, and SQSTM1/p62 suppression were observed. Administration of autophagy inhibitor (bafilomycin A1 and chloroquine) and transfection of a tandem fluorescent-tagged LC3 (mRFP-GFP) reporter plasmid (ptfLC3) demonstrated that JA induces autophagy flux in HT-29 cells. Expression of LC3, SQSTM1, Beclin 1, and nuclear DNA double-strand breaks (representing apoptosis) were also detected in the tumor tissue of HT-29 cells transplanted into NOD-SCID mice orally administrated with JA. In addition, the expression of autophagy signaling pathway-related molecules p-PDK1, p-mTOR, p-p70S6k/p-RPS6KB2 was decreased, whereas that of class III PI3K, Beclin 1, Atg5-Atg12, and mitochondrial BNIP3 was increased in response to JA. Pre-treatment of the cells with class III PI3K inhibitor 3-methyladenine or Atg5 shRNA attenuated JA-induced LC3-II expression and LC3 puncta formation, indicating the involvement of class III PI3K and Atg5. A novel mechanism was demonstrated in the anticancer compound JA; pre-treatment with 3-methyladenine or Atg5 shRNA blocked JA-induced suppression in cell growth and colony formation, respectively, via inhibition of apoptosis. In contrast, administration of apoptosis inhibitor Z-VAD did not affect JA-induced autophagy. Our data suggest the chemotherapeutic potential of JA for treatment of human colorectal cancer.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Dioxolanos/farmacologia , Lignanas/farmacologia , Proteínas Associadas aos Microtúbulos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Proteína 5 Relacionada à Autofagia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Células HT29 , Humanos , Camundongos , Camundongos SCID , RNA Interferente Pequeno/metabolismo
12.
Apoptosis ; 20(11): 1471-82, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26349782

RESUMO

A number of effective anti-cancer drugs contain either indole or quinoline group. Compounds fused indole and quinoline moieties altogether as indolylquinoline were rarely reported as anti-cancer agents. We reported here that a synthetic indolylquinoline derivative, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), inhibited the growth of human non-small cell lung cancer (NSCLC) cells in dose- and time-dependent manners. The cytotoxicity was mediated through apoptotic cell death that began with mitochondrial membrane potential interruption and DNA damage. EMMQ caused transient elevation of p53 that assists in cytochrome c release, cleavage of downstream PARP and procaspase-3 and mitochondria-related apoptosis. The degree of apoptotic cell death depends on the status of tumor suppressor p53 of the target cells. H1299 cells with stable ectopic expression of p53 induced cytotoxicity by disrupting mitochondria functions that differed with those transfected with mutant p53. Knocking-down of p53 attenuated drug effects. EMMQ suppressed the growth of A549 tumor cells in xenograft tumors by exhibiting apoptosis characteristics. Given its small molecular weight acting as an effective p53 regulator in NSCLC cells, EMMQ could be an addition to the current list of lung cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Indóis/farmacologia , Neoplasias Pulmonares/fisiopatologia , Mitocôndrias/efeitos dos fármacos , Quinolinas/farmacologia , Antineoplásicos/química , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Citocromos c/metabolismo , Dano ao DNA/efeitos dos fármacos , Humanos , Indóis/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mitocôndrias/metabolismo , Quinolinas/química , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
13.
Ecotoxicology ; 23(10): 1922-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25142350

RESUMO

Species differences in inorganic arsenic tolerance were investigated by comparing the responses of Bacillus subtilis (B. subtilis) and Bacillus thuringiensis (B. thuringiensis) to elevated concentrations of As(III) and As(V). The cell densities in treatments were always lower during the experiment compared to controls, with the exception of exposure to 1.0 mg As(V) l(-1) on the first day. It was also found that relative growth rate (RGR) of B. thuringiensis was lower than that of B. subtilis. Furthermore, RGR of each Bacillus species was negative correlation with toxicity of inorganic arsenic. However, total cell number still increased in each treatment according to cell density and RGR assays. Superoxide dismutase (SOD) activity of both Bacillus species was promoted by As(III) and As(V), especially under high arsenic concentration condition. In addition, SOD activity of B. thuringiensis was higher than that of B. subtilis during the same exposure time. In lipid peroxidation assay, thiobarbituric acid-reactive substances (TBARS) content of each Bacillus species had a significant increase with increment of arsenic concentration. Moreover, significant difference was observed between the two Bacillus species under high arsenic concentration. TBARS content of B. thuringiensis was higher than that of B. subtilis, indicating that effect of arsenic on cell membranes of B. thuringiensis was much more than that of B. subtilis. These results suggest that the two Bacillus species could adapt and live in high arsenic aquifers, although their growth and cell membranes were affected by As treatment in a way.


Assuntos
Arsênio/metabolismo , Bacillus/fisiologia , Substâncias Perigosas/metabolismo , Superóxido Dismutase/metabolismo , Biodegradação Ambiental , Peroxidação de Lipídeos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
14.
Int J Food Sci Nutr ; 65(3): 368-74, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24438326

RESUMO

Curcumin, an active natural compound in turmeric and curry, has been reported to exhibit anti-cancer effect. Cisplatin, carboplatin and oxaliplatin are used to treat various types of cancers. However, acquired resistance and toxicities are observed. Here, the addition of curcumin significantly increased cytotoxicity of the anti-cancer drugs on human colorectal cancer HT-29 cells, producing synergistic (cisplatin and carboplatin) and additivity (oxaliplatin) effects. Treatments in combination with curcumin resulted in a significantly increased induction of apoptosis and occurrence of G2/M arrest. Nuclear apoptosis-inducing factor (AIF), EndoG and NF-κB were elevated by anti-cancer drugs, suggesting the involvement of AIF and EndoG. The addition of curcumin suppressed nuclear AIF and EndoG and reversed anti-cancer drugs-induced NF-κB expression, suggesting the association of EndoG and NF-κB in curcumin-enhanced chemosensitivity. Therefore, the intake of foods rich in curcumin or curcumin-containing supplements should be taken into consideration for patients receiving chemotherapy to optimize the outcome of treatments.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Curcuma/química , Curcumina/uso terapêutico , Endodesoxirribonucleases/metabolismo , NF-kappa B/metabolismo , Fitoterapia , Platina/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Pontos de Checagem do Ciclo Celular , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Curcumina/farmacologia , Regulação para Baixo , Sinergismo Farmacológico , Células HT29 , Humanos , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Platina/farmacologia
15.
Materials (Basel) ; 17(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38473597

RESUMO

The continuous growth of industrial solid waste production has generated many environmental problems. We evaluated the potential of industrial solid waste as a substitute filler in asphalt mastic, with the aim of increasing the use of sustainable road construction materials. In this study, X-ray fluorescence spectroscopy (XRF) and scanning electron microscopy (SEM) were used to characterize the oxide composition and micromorphology of limestone (LS), red mud (RM), steel slag (SS), and ground granulated blast-furnace slag (GGBFS). Four asphalt mastics containing LS, RM, SS, and GGBFS with a filler-to-binder weight ratio of one were prepared. An evaluation of the rheology and wetting of the solid-waste-filler asphalt mastic was conducted using a frequency sweep, temperature sweep, linear amplitude sweep (LAS), multiple stress creep and recovery (MSCR), and surface free energy (SFE) methods. The results showed that SS increased the complex modulus, elastic component of the asphalt mastic and decreased the nonrecoverable creep compliance at stress levels of 0.1 and 3.2 kPa, which improved the rutting resistance of the asphalt mastic and reduced deformation under high-temperature conditions. The RM and GGBFS increased the fatigue performance of the asphalt mastic under strain loading, enhanced its fatigue life, and maintained good performance under long-term loading. The dispersive component of the SFE parameter of the solid-waste-filler asphalt mastic was larger than the polar component for the largest share of the surface energy composition. The SFE of the asphalt mastic prepared from the industrial solid-waste filler was reduced; however, the difference was insignificant compared to the limestone asphalt mastic. Solid-waste-filler asphalt mastic has performance characteristics, and its actual application can be based on different performance characteristics to select an appropriate solid-waste filler. The results of this study provide new technological solutions for solving the utilization rate of solid waste materials and sustainable road construction in the future.

16.
Toxicol Appl Pharmacol ; 273(1): 110-20, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23954467

RESUMO

In this work, we demonstrated that the growth of human non-small-cell-lung-cancer cells H460 and A549 cells can be inhibited by low concentrations of an epoxide derivative, teroxirone, in both in vitro and in vivo models. The cytotoxicity was mediated by apoptotic cell death through DNA damage. The onset of ultimate apoptosis is dependent on the status of p53. Teroxirone caused transient elevation of p53 that activates downstream p21 and procaspase-3 cleavage. The presence of caspase-3 inhibitor reverted apoptotic phenotype. Furthermore, we showed the cytotoxicity of teroxirone in H1299 cells with stable ectopic expression of p53, but not those of mutant p53. A siRNA-mediated knockdown of p53 expression attenuated drug sensitivity. The in vivo experiments demonstrated that teroxirone suppressed growth of xenograft tumors in nude mice. Being a potential therapeutic agent by restraining cell growth through apoptotic death at low concentrations, teroxirone provides a feasible perspective in reversing tumorigenic phenotype of human lung cancer cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Triazinas/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Anexina A5/genética , Anexina A5/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Citocromos c/metabolismo , Dano ao DNA/efeitos dos fármacos , Regulação para Baixo , Humanos , Camundongos , Camundongos Nus , RNA Interferente Pequeno/genética , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Water Environ Res ; 85(2): 113-23, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23472327

RESUMO

To better understand the effects of recharge and discharge on the hydrogeochemistry of high levels of arsenic (As) and fluoride (F) in groundwater, environmental isotopic composition (delta2H and delta18O) and chloride (Cl) concentrations were analyzed in 29 groundwater samples collected from the Datong Basin. High arsenic groundwater samples (As > 50 micog/L) were found to be enriched in lighter isotopic composition that ranged from -92 to -78 per thousand for deuterium (delta2H) and from -12.5 to -9.9 per thousand for oxygen-18 (delta18O). High F-containing groundwater (F > 1 mg/L) was relatively enriched in heavier isotopic composition and varied from -90 to -57 per thousand and from -12.2 to -6.7 per thousand for delta2H and delta18O, respectively. High chloride concentrations and delta18O values were primarily measured in groundwater samples from the northern and southwestern portions of the study area, indicating the effect of evaporation on groundwater. The observation of relatively homogenized and low delta18O values and chloride concentrations in groundwater samples from central part of the Datong Basin might be a result of fast recharge by irrigation returns, which suggests that irrigation using arsenic-contaminated groundwater affected the occurrence of high arsenic-containing groundwater in the basin.


Assuntos
Arsênio/análise , Cloretos/análise , Deutério/análise , Fluoretos/análise , Água Subterrânea/análise , China , Monitoramento Ambiental , Isótopos de Oxigênio/análise , Rios , Poluentes Químicos da Água/análise , Poluição Química da Água/análise
18.
Artigo em Inglês | MEDLINE | ID: mdl-36767199

RESUMO

The exposure of inhabitants to high fluoride and saline groundwater is the main health issue in Datong Basin, Northern China. This study aims to elucidate the spatial distribution and the mechanisms of high fluoride and salinity occurrence in the shallow sedimentary aquifers of the Datong Basin. Groundwater salinity and fluoride content, and their association with measured hydrochemical parameters, were conducted using multivariate statistical analyses. The analytical results revealed that the concentrations of fluoride and total dissolved solids (TDS) show dramatic variations within the study area. Around 41.4% of groundwater samples contained high-level fluoride concentration (F- > 1.5 mg/L), whereas 32.8% contained elevated-level TDS (TDS > 1000 mg/L). Both fluoride and TDS concentrations had elevated trends towards the central part of the basin. Shallow groundwater was seriously affected by evaporation and evapotranspiration, which can be the critical factors responsible for rather high TDS and F- concentrations in shallow aquifers. Water-rock reactions including silicate hydrolysis, dissolution-precipitation of carbonates and evaporates, adsorption, and ion exchange processes, as well as evapotranspiration, are the main governing factors for salinity and fluoride enrichment in groundwater. Solubility control of F-bearing and carbonate minerals is the dominant mechanism affecting F- levels. Prevailing conditions of alkaline pH, moderate TDS and Na+, high HCO3-, and lower Ca2+ content facilitate the enrichment of fluoride in the study area. Excessive evapotranspiration can be also the most influencing factor responsible for high fluoride and TDS content, due to the extended residence time of groundwater and the arid climate of the central part of the Datong Basin.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Fluoretos/análise , Salinidade , Monitoramento Ambiental , Água Subterrânea/química , China , Poluentes Químicos da Água/análise
19.
Artigo em Inglês | MEDLINE | ID: mdl-37702864

RESUMO

Groundwater quality is influenced by urbanization and land use land cover (LULC) changes. This study investigated their impact on groundwater quality in Quetta City, Pakistan, from 2015 to 2021. About 58 groundwater samples from monitoring wells were analyzed using hydrogeochemical and statistical methods. The water quality index (WQI), Wilcox, USSL, and various agricultural indices were employed to assess water quality trends. LULC analysis and NDVI using Sentinel-2 imagery revealed increased urban and agricultural areas and decreased barren land. Rapid urbanization was evident, with the buildup class expanding by 7.50% during this period. NDVI findings emphasized monitoring vegetation health and water quality for environmental assessments. The groundwater in Quetta was primarily classified as Cl-Ca·Mg, Cl-Ca, and Cl-Na according to the Piper diagram, with water-rock interactions and rock weathering evident. Most groundwater samples were suitable for irrigation according to the Wilcox and USSL diagrams. The WQI demonstrated overall safety for human consumption, but declining WQI values in northern parts due to urbanization are concerning. The results also revealed a moderate positive relationship between landcover classes and WQI values. It can be concluded that urbanization and excessive use of pesticides contributed to declining agricultural land quality. The spatial overlay of agricultural indices with landcover class suggested that barren land was most suitable, followed by build-up and agriculture were suitable for drinking and agriculture purposes. Moreover, agricultural indices moderately declined due to excessive fertilizers and pesticides in the agriculture landcover class. Thus, effective water resource management is crucial to address challenges. This comprehensive study serves as a baseline for future research and recommends larger-scale studies to implement efficient management strategies, urbanization planning, and safe irrigation and drinking water practices to prevent groundwater pollution.

20.
Front Microbiol ; 14: 1294182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38274755

RESUMO

Saccharomyces cerevisiae is a eukaryotic organism with a clear genetic background and mature gene operating system; in addition, it exhibits environmental tolerance. Therefore, S. cerevisiae is one of the most commonly used organisms for the synthesis of biological chemicals. The investigation of fatty acid catabolism in S. cerevisiae is crucial for the synthesis and accumulation of fatty acids and their derivatives, with ß-oxidation being the predominant pathway responsible for fatty acid metabolism in this organism, occurring primarily within peroxisomes. The latest research has revealed distinct variations in ß-oxidation among different fatty acids, primarily attributed to substrate preferences and disparities in the metabolic regulation of key enzymes involved in the S. cerevisiae fatty acid metabolic pathway. The synthesis of lipids, on the other hand, represents another crucial metabolic pathway for fatty acids. The present paper provides a comprehensive review of recent research on the key factors influencing the efficiency of fatty acid utilization, encompassing ß-oxidation and lipid synthesis pathways. Additionally, we discuss various approaches for modifying ß-oxidation to enhance the synthesis of fatty acids and their derivatives in S. cerevisiae, aiming to offer theoretical support and serve as a valuable reference for future studies.

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