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1.
J Agric Food Chem ; 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38607803

RESUMEN

The occurrence of maize ear rot caused by Fusarium verticillioides (F. verticillioides) poses a threat to the yield and quality of maize. Mefentrifluconazole enantiomers appear to have strong stereoselective activity against F. verticillioides and cause differences in fumonisin production. We evaluated the stereoselective activity of mefentrifluconazole enantiomers by determining inhibition of the strain, hyphae, and conidia. Strain inhibition by R-(-)-mefentrifluconazole was 241 times higher than S-(+)-mefentrifluconazole and 376 times higher in conidia inhibition. For the mechanism of the enantioselective bioactivity, R-mefentrifluconazole had stronger binding to proteins than S-(+)-mefentrifluconazole. Under several concentration conditions, the fumonisin concentration was 1.3-24.9-fold higher in the R-(-)-mefentrifluconazole treatment than in the S-(+)-mefentrifluconazole treatment. The R-enantiomer stimulated fumonisin despite a higher bioactivity. As the incubation time increased, the stimulation of the enantiomers on fumonisin production decreased. R-(-)-Mefentrifluconazole stimulated higher fumonisin production in F. verticillioides at 25 °C compared to 30 °C. This study established a foundation for the development of high-efficiency and low-risk pesticides.

2.
Front Oncol ; 14: 1334915, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38515577

RESUMEN

The dry root of the soybean plant Astragalus membranaceus (Fisch) Bge. var. mongholicus (Bge) Hsiao or A. membranaceus (Fisch) Bge, Astragali Radix (AR) has a long medicinal history. Astragalus polysaccharide (APS), the natural macromolecule that exhibits immune regulatory, anti-inflammatory, anti-tumor, and other pharmacological activities, is an important active ingredient extracted from AR. Recently, APS has been increasingly used in cancer therapy owing to its anti-tumor ability as it prevents the progression of prostate, liver, cervical, ovarian, and non-small-cell lung cancer by suppressing tumor cell growth and invasion and enhancing apoptosis. In addition, APS enhances the sensitivity of tumors to antineoplastic agents and improves the body's immunity. This macromolecule has prospects for broad application in tumor therapy through various pathways. In this article, we present the latest progress in the research on the anti-tumor effects of APS and its underlying mechanisms, aiming to provide novel theoretical support and reference for its use in cancer therapy.

3.
Ecotoxicol Environ Saf ; 272: 116019, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38295734

RESUMEN

Agricultural production relies heavily on pesticides. However, factors like inefficient application, pesticide resistance, and environmental conditions reduce their effective utilization in agriculture. Subsequently, pesticides transfer into the soil, adversely affecting its physicochemical properties, microbial populations, and enzyme activities. Different pesticides interacting can lead to combined toxicity, posing risks to non-target organisms, biodiversity, and organism-environment interactions. Pesticide exposure may cause both acute and chronic effects on human health. Biochar, with its high specific surface area and porosity, offers numerous adsorption sites. Its stability, eco-friendliness, and superior adsorption capabilities render it an excellent choice. As a versatile material, biochar finds use in agriculture, environmental management, industry, energy, and medicine. Added to soil, biochar helps absorb or degrade pesticides in contaminated areas, enhancing soil microbial activity. Current research primarily focuses on biochar produced via direct pyrolysis for pesticide adsorption. Studies on functionalized biochar for this purpose are relatively scarce. This review examines biochar's pesticide absorption properties, its characteristics, formation mechanisms, environmental impact, and delves into adsorption mechanisms, functionalization methods, and their prospects and limitations.


Asunto(s)
Plaguicidas , Contaminantes del Suelo , Humanos , Plaguicidas/química , Adsorción , Contaminantes del Suelo/análisis , Carbón Orgánico/química , Suelo/química , Biodiversidad
4.
Biomed Pharmacother ; 170: 116097, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38160624

RESUMEN

α-Hederin is a monosaccharide pentacyclic triterpene saponin compound derived from the Chinese herb, Pulsatilla. It has garnered considerable attention for its anti-tumor, anti-inflammatory, and spasmolytic pharmacological activities. Given the rising incidence of cancer and the pronounced adverse reactions associated with chemotherapy drugs-which profoundly impact the quality of life for cancer patients-there is an immediate need for safe and effective antitumor agents. Traditional drugs and their anticancer effects have become a focal point of research in recent years. Studies indicate that α-Hederin can hinder tumor cell proliferation and impede the advancement of various cancers, including breast, lung, colorectal, and liver cancers. The principal mechanism behind its anti-tumor activity involves inhibiting tumor cell proliferation, facilitating tumor cell apoptosis, and arresting the cell cycle process. Current evidence suggests that α-Hederin can exert its anti-tumor properties through diverse mechanisms, positioning it as a promising agent in anti-tumor therapy. However, a comprehensive literature search revealed a gap in the comprehensive understanding of α-Hederin. This paper aims to review the available literature on the anti-tumor mechanisms of α-Hederin, hoping to provide valuable insights for the clinical treatment of malignant tumors and the innovation of novel anti-tumor medications.


Asunto(s)
Antineoplásicos , Neoplasias Hepáticas , Ácido Oleanólico , Saponinas , Humanos , Línea Celular Tumoral , Calidad de Vida , Saponinas/farmacología , Saponinas/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ácido Oleanólico/farmacología , Ácido Oleanólico/uso terapéutico
5.
Bioorg Med Chem ; 95: 117486, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37847948

RESUMEN

Chemotherapy is the mainstay in the treatment of breast cancer. However, many drugs that are commonly used in clinical practice have a high incidence of side effects and multidrug resistance (MDR), which is mainly caused by overexpression of drug transporters and related enzymes in breast cancer cells. In recent years, researchers have been working hard to find newer and safer drugs to overcome MDR in breast cancer. In this review, we provide the molecule mechanism of MDR in breast cancer, categorize potential lead compounds that inhibit single or multiple drug transporter proteins, as well as related enzymes. Additionally, we have summarized the structure-activity relationship (SAR) based on potential breast cancer MDR modulators with lower side effects. The development of novel approaches to suppress MDR is also addressed. These lead compounds hold great promise for exploring effective chemotherapy agents to overcome MDR, providing opportunities for curing breast cancer in the future.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos , Resistencia a Múltiples Medicamentos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico
6.
Pest Manag Sci ; 79(12): 4784-4794, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37471098

RESUMEN

BACKGROUND: Yield loss and toxin contamination caused by wheat Fusarium head blight (FHB) have always been a worldwide concern. Cultivating disease-resistant varieties and fungicide application are effective measures to control FHB. The comprehensive control technology system for FHB and toxin contamination of wheat in Anhui Province needs further improvement. This study compared the control efficacy of different wheat varieties, fungicides and application times on wheat FHB and deoxynivalenol (DON) contamination, and the dynamic change of DON accumulation after application. RESULTS: Among the 93 main wheat varieties in Anhui Province, the disease-resistant and low-toxic wheat variety "Ningmai 26" was more suitable for planting in the central part of Anhui Province. At the same time, "Yangmai 22" was used for subsequent experiments. The field efficacy trials of different fungicides showed that 30% prothioconazole oil dispersion (OD) had the highest control efficacy on FHB and DON contamination, reaching 94.33 and 77.49%, respectively. The study on the optimum application time of prothioconazole showed that the 0-20% flowering stage was the key point of DON control. The survey of the dynamic changes of DON accumulation showed that prothioconazole could significantly reduce the level of DON accumulation while inhibiting the accumulation rate of DON. At the same time, the control fungicide carbendazim increased the level of DON contamination. CONCLUSION: This study will provide excellent germplasm resources for cultivating disease-resistant and low-toxic wheat varieties, and provide a theoretical reference for establishing a collaborative prevention and control system of disease control and toxin reduction. © 2023 Society of Chemical Industry.


Asunto(s)
Fungicidas Industriales , Fusarium , Tricotecenos , Triticum , Fungicidas Industriales/farmacología , Enfermedades de las Plantas/prevención & control
7.
Pharmacol Rep ; 75(4): 891-906, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37202657

RESUMEN

Cancer is a significant disease that poses a major threat to human health. The main therapeutic methods for cancer include traditional surgery, radiotherapy, chemotherapy, and new therapeutic methods such as targeted therapy and immunotherapy, which have been developed rapidly in recent years. Recently, the tumor antitumor effects of the active ingredients of natural plants have attracted extensive attention. Ferulic acid (FA), (3-methoxy-4-hydroxyl cinnamic), with the molecular formula is C10H10O4, is a phenolic organic compound found in ferulic, angelica, jujube kernel, and other Chinese medicinal plants but is also, abundant in rice bran, wheat bran, and other food raw materials. FA has anti-inflammatory, analgesic, anti-radiation, and immune-enhancing effects and also shows anticancer activity, as it can inhibit the occurrence and development of various malignant tumors, such as liver cancer, lung cancer, colon cancer, and breast cancer. FA can cause mitochondrial apoptosis by inducing the generation of intracellular reactive oxygen species (ROS). FA can also interfere with the cell cycle of cancer cells, arrest most cancer cells in G0/G1 phase, and exert an antitumor effect by inducing autophagy; inhibiting cell migration, invasion, and angiogenesis; and synergistically improving the efficacy of chemotherapy drugs and reducing adverse reactions. FA acts on a series of intracellular and extracellular targets and is involved in the regulation of tumor cell signaling pathways, including the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT), B-cell lymphoma-2 (Bcl-2), and tumor protein 53 (P53) pathways and other signaling pathways. In addition, FA derivatives and nanoliposomes, as platforms for drug delivery, have an important regulatory effect on tumor resistance. This paper reviews the effects and mechanisms of antitumor therapies to provide new theoretical support and insight for clinical antitumor therapy.


Asunto(s)
Neoplasias Pulmonares , Fosfatidilinositol 3-Quinasas , Humanos , Proliferación Celular , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Ácidos Cumáricos/farmacología , Ácidos Cumáricos/uso terapéutico , Apoptosis , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/metabolismo
8.
Sci Total Environ ; 874: 162585, 2023 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-36870510

RESUMEN

Honey bees play an important role in the ecological environment. Regrettably, a decline in honey bee colonies caused by chemical insecticides has occurred throughout the world. Potential stereoselective toxicity of chiral insecticides may be a hidden source of danger to bee colonies. In this study, the stereoselective exposure risk and mechanism of malathion and its chiral metabolite malaoxon were investigated. The absolute configurations were identified using an electron circular dichroism (ECD) model. Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for chiral separation. In pollen, the initial residues of malathion and malaoxon enantiomers were 3571-3619 and 397-402 µg/kg, respectively, and R-malathion degraded relatively slowly. The oral LD50 values of R-malathion and S-malathion were 0.187 and 0.912 µg/bee with 5 times difference, respectively, and the malaoxon values were 0.633 and 0.766 µg/bee. The Pollen Hazard Quotient (PHQ) was used to evaluate exposure risk. R-malathion showed a higher risk. An analysis of the proteome, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and subcellular localization, indicated that energy metabolism and neurotransmitter transport were the main affected pathways. Our results provide a new scheme for the evaluation of the stereoselective exposure risk of chiral pesticides to honey bees.


Asunto(s)
Insecticidas , Violación , Abejas , Animales , Malatión/toxicidad , Malatión/química , Insecticidas/toxicidad , Insecticidas/análisis , Proteoma , Cromatografía Liquida , Espectrometría de Masas en Tándem
9.
J Agric Food Chem ; 71(3): 1426-1433, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36630283

RESUMEN

Fluindapyr is a novel chiral succinate dehydrogenase inhibitor used to control fungal diseases. The enantioselective effects of fluindapyr in paddy ecosystems are unknown. We developed a new chiral determination method of fluindapyr using ultrahigh performance liquid chromatography tandem mass spectrometry. The absolute configuration of the fluindapyr enantiomers was identified by an electron circular dichroism model. A new husk-based biochar material was used to optimize and establish a QuEchERs method for paddy soil determination. Under anaerobic conditions, the half-lives of R-fluindapyr and S-fluindapyr in paddy soil were 69.6 and 101.8 days, respectively. R-fluindapyr degraded more rapidly than S-fluindapyr. S-fluindapyr was 87.8 times more active against Rhizoctonia solani than R-fluindapyr. The enantioselective bioactivity mechanism was illustrated by molecular docking between the fluindapyr enantiomers and SDH of R. solani. The binding powers of R-fluindapyr and S-fluindapyr to proteins were -32.12 and - 42.91 kcal/mol, respectively. This study reports the stereoselectivity of fluindapyr about determination, degradation, bioactivity, and its mechanism. It provides a foundation for an in-depth study of fluindapyr at the enantiomer level.


Asunto(s)
Fungicidas Industriales , Contaminantes del Suelo , Fungicidas Industriales/química , Ecosistema , Estereoisomerismo , Simulación del Acoplamiento Molecular , Contaminantes del Suelo/química , Espectrometría de Masas en Tándem/métodos , Suelo/química
10.
Molecules ; 28(2)2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36677638

RESUMEN

Chlorfenapyr, as a highly effective and low-toxicity insect growth regulation inhibitor, has been used to control cross-cruciferous vegetable pests. However, the pesticide residue caused by its application threatens human health. In this paper, the residue digestion and final residue of chlorfenapyr in radish were studied in a field experiment. The results of the dynamic digestion test showed that the half-life of chlorfenapyr in radish leaves ranged from 6.0 to 6.4 days, and the digestion rate was fast. The median residual values of chlorfenapyr in radish and radish leaves at 14 days after treatment were 0.12 and 3.92 mg/kg, respectively. The results of the dietary intake risk assessment showed that the national estimated daily intake (NEDI) of chlorfenapyr in various populations in China were 0.373 and 5.66 µg/(kg bw·d), respectively. The risk entropy (RQ) was 0.012 and 0.147, respectively, indicating that the chronic dietary intake risk of chlorfenapyr in radish was low. The results of this study provided data support and a theoretical basis for guiding the scientific use of chlorfenapyr in radish production and evaluating the dietary risk of chlorfenapyr in vegetables.


Asunto(s)
Insecticidas , Residuos de Plaguicidas , Piretrinas , Raphanus , Humanos , Piretrinas/análisis , Residuos de Plaguicidas/análisis , Medición de Riesgo , Insecticidas/análisis
11.
Oncol Rep ; 49(1)2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36416347

RESUMEN

Tumors are one of the most common fatal diseases worldwide and pose a severe threat to human health. Effective tumor prevention and treatment strategies are persistent challenges in the medical community. Angiogenesis plays a critical role in and is the basis for tumor development and metastasis. Circular RNAs (circRNAs) are novel single­stranded covalently closed RNA molecules that are widely expressed in tumors due to their structural specificity and conservation. circRNAs affect angiogenesis by functioning as microRNA sponges to regulate vascular endothelial growth factor­related pathways, thereby participating in various stages of tumor growth, invasion and proliferation. The present review summarizes the involvement of circRNAs in the regulation of tumor angiogenesis through competing endogenous RNA mechanisms, with a particular focus on the regulatory role of circRNAs in tumor angiogenesis in various systems. It is considered that circRNAs have great potential for use as tumor diagnostic markers and anti­angiogenic therapies, and are thus worthy of further research and exploration.


Asunto(s)
MicroARNs , Neoplasias , Humanos , ARN Circular/genética , Factor A de Crecimiento Endotelial Vascular , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/genética , Biomarcadores de Tumor
12.
Ecotoxicol Environ Saf ; 241: 113784, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35738101

RESUMEN

Sedaxane was a novel chiral fungicide that contains four enantiomers. Unfortunately, the stereoselective bioactivity, toxicity and degradation of sedaxane have not been clarified. In this study, we identified the absolute configuration of the four sedaxane enantiomers at first time. The stereoselective bioactivity toward three wheat and rice pathogens, stereoselective acute toxicity to aquatic organisms (Selenastrum capricornutum and Daphnia magna), and stereoselective degradation of sedaxane were studied. The 1 S,2S-(+)-sedaxane possessed 5.4-7.3 times greater bioactivity than 1 R,2R-(-)-sedaxane to Rhizoctonia solani and Rhizoctonia cerealis. Contrarily, the 1 R,2S-(+)-sedaxane had 4.2 times greater activity than 1 S,2S-(+)-sedaxane against Fusarium graminearum. The 1 R,2R-(-)-sedaxane had 2.8 times greater toxicity than 1 S,2S-(+)-sedaxane to S. capricornutum. The chiral determination method used ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The recovery of sedaxane stereoisomers ranged from 83.1 % to 98.2 %, with RSDs (Relative standard deviations) of 1.2 %- 8.4 %. The trans-sedaxane existed stereoselective degradation phenomenon in the rice-wheat rotation mode, and 1 S,2S-(+)-sedaxane was preferentially degraded. Our results would provide scientific importance and practical guidance to the safety evaluation of chiral pesticides.


Asunto(s)
Fungicidas Industriales , Oryza , Anilidas , Cromatografía Liquida , Fungicidas Industriales/química , Fungicidas Industriales/toxicidad , Pirazoles , Estereoisomerismo , Espectrometría de Masas en Tándem/métodos , Triazoles/química , Triticum
13.
Pest Manag Sci ; 78(7): 3012-3018, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35426212

RESUMEN

BACKGROUND: Balancing the safety and efficiency of chiral pesticides can help protect pollinators. We evaluated the stereoselective behavior, bioactivity, toxicity and exposure risk of the chiral insecticide pyriproxyfen in a citrus nectar system. RESULTS: Density functional theory (DFT) and ultra-performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS) were applied for absolute configuration appraisal and chiral analysis validation, respectively. The recoveries ranged from 72.3% to 100.5% with an relative standard deviation (RSD) ranging from 1.2% to 9.7%. In a field trial, we determined insecticide half-lives in citrus leaves and flowers, which were 7.0 and 8.6 days for R-(+)-pyriproxyfen, and 11.7 and 14.7 days for S-(-)-pyriproxyfen, respectively. We found that the bioactivity of R-(+)-pyriproxyfen was 3.39 and 2.37 times higher than S-(-)-pyriproxyfen against Unaspis yanonensis and Diaphorina citri nymphs, respectively. S-(-)-pyriproxyfen had 3.8 times higher acute toxicity than R-(+)-pyriproxyfen on Apis mellifera L., and its exposure risk was moderate based on the hazard quotient. CONCLUSION: The phenomenon of stereoselective degradation and biological effect demonstrated that the high-risk stereoisomer of S-(-)-pyriproxyfen degraded more slowly than R-(+)-pyriproxyfen, but R-(+)-pyriproxyfen with better efficiency for target. Therefore, an increased duration of R-(+)-pyriproxyfen activity on citrus was beneficial for efficacy. Our results could guide the scientific application and evaluation of chiral pesticides on nectar plants. © 2022 Society of Chemical Industry.


Asunto(s)
Citrus , Hemípteros , Insecticidas , Plaguicidas , Animales , Abejas , Cromatografía Liquida , Insecticidas/toxicidad , Plaguicidas/análisis , Néctar de las Plantas , Piridinas , Estereoisomerismo , Espectrometría de Masas en Tándem/métodos
14.
Front Med (Lausanne) ; 9: 1052540, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36687445

RESUMEN

Ferroptosis, a new type of cell death, is mainly characterized by intracellular iron accumulation and lipid peroxidation. The complex regulatory network of iron metabolism, lipid metabolism, amino acid metabolism, p53-related signaling, and Nrf2-related signaling factors is involved in the entire process of ferroptosis. It has been reported that ferroptosis is involved in the pathogenesis of neurological diseases, cancer, and ischemia-reperfusion injury. Recent studies found that ferroptosis is closely related to the pathogenesis of COPD, which, to some extent, indicates that ferroptosis is a potential therapeutic target for COPD. This article mainly discusses the related mechanisms of ferroptosis, including metabolic regulation and signaling pathway regulation, with special attention to its role in the pathogenesis of COPD, aiming to provide safe and effective therapeutic targets for chronic airway inflammatory diseases.

15.
Pak J Pharm Sci ; 34(3(Special)): 1271-1276, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34602399

RESUMEN

The research on bioactive secondary metabolites from Aspergillus fumigatus afforded six compounds, which were identified by mass spectrometer (MS) and nuclear magnetic resonance (NMR) spectroscopic analysis as cyclopyazonic acid (1), trypacidin A (2), asterric acid (3), methyl asterrate (4), demethylcitreoviranol (5), as well as (5-hydroxy-2-oxo-2H-pyran-4-yl) methyl acetate (6). Cyclopyazonic acid (1) was found to have potent antibacterial effects, especially against Bacillus licheniformis with minimal inhibitory concentration (MIC) value of 3.7µg/mL. Its antibacterial effects were possibly related to the olefinic acid group in the structure. Phenyl ether derivatives 3 and 4, and trypacidin A (2) also exhibited antimicrobial effects. In addition, compound 6 showed significant antioxidant effects with half maximal effective concentration (EC50) value of 10.2µM in the ABTS (2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) assay, which was better than the positive control.


Asunto(s)
Antibacterianos/farmacología , Antioxidantes/farmacología , Aspergillus fumigatus/metabolismo , Acetatos/química , Acetatos/farmacología , Animales , Aspergillus fumigatus/química , Bacillus/efectos de los fármacos , Bacillus licheniformis/efectos de los fármacos , Bacillus subtilis/efectos de los fármacos , Espectroscopía de Resonancia Magnética con Carbono-13 , Escherichia coli/efectos de los fármacos , Indoles/química , Indoles/farmacología , Insectos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Micotoxinas/farmacología , Fenoles/química , Fenoles/farmacología , Éteres Fenílicos/química , Éteres Fenílicos/farmacología , Espectroscopía de Protones por Resonancia Magnética , Pseudomonas aeruginosa/efectos de los fármacos , Piranos/química , Piranos/farmacología , Staphylococcus aureus/efectos de los fármacos
16.
Pharmacol Res ; 173: 105900, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34547385

RESUMEN

Phosphatidylinositol 3-kinases (PI3Ks) are the family of vital lipid kinases widely distributed in mammalian cells. The overexpression of PI3Ks leads to hyperactivation of the PI3K/AKT/mTOR pathway, which is considered a pivotal pathway in the occurrence and development of tumors. Hence, PI3Ks are viewed as promising therapeutic targets for anti-cancer therapy. To date, some PI3K inhibitors have achieved desired therapeutic effect via inhibiting the activity of PI3Ks or reducing the level of PI3Ks in clinical trials, among which, Idelalisib, Alpelisib and Duvelisib have been approved by the FDA for treatment of ER+/HER2- advanced metastatic breast cancer and refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphomas (SLL). This review focuses on the latest advances of PI3K inhibitors with efficacious anticancer activity, which are classified into Pan-PI3K inhibitors, isoform-specific PI3K inhibitors and dual PI3K/mTOR inhibitors based on the isoform affinity. Their corresponding structure characteristics and structures-activity relationship (SAR), together with the progress in the clinical application are mainly discussed. Additionally, the new PI3K inhibitory strategy, such as PI3K degradation agent, for the design of potential PI3K candidates to overcome drug resistance is referred as well.


Asunto(s)
Antineoplásicos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Isoenzimas/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/química , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3/uso terapéutico , Proteolisis , Relación Estructura-Actividad , Serina-Treonina Quinasas TOR/antagonistas & inhibidores
17.
Int J Pharm ; 603: 120644, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33964335

RESUMEN

Breast cancer is one of the most common malignant tumors among women population on a global scale, with a huge number of new cases and deaths each year. In recent years, there has been an increasing number of literatures on the discovery and development of novel anti-breast cancer drugs and materials, aiming to increase the survival rate of breast cancer patients. One of the newest tools used for the therapy of breast cancer is graphene-based materials, which have ultra-high surface area as well as unique physical, chemical and mechanical properties. It is reported that graphene-based materials could induce apoptosis in cancer cells while showing low toxicity due to their carbon structure. Therefore, they can be used as nano-drugs or biological carriers to introduce small molecules such as nucleic acids, drugs, or photosensitizers into the human body to achieve treatment goals. This article introduces the synthetic methods for graphene-based materials, as well as the current status and the future prospects of graphene-based materials' application in the treatment of breast cancer.


Asunto(s)
Neoplasias de la Mama , Grafito , Neoplasias de la Mama/tratamiento farmacológico , Carbono , Femenino , Humanos
18.
Biomed Res Int ; 2020: 7467104, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33376737

RESUMEN

Gastric carcinoma is a common malignant cancer. Pyruvate kinase M2 (PKM2) is highly expressed in cancers, including gastric carcinoma. However, its function and molecular mechanism in gastric carcinoma remains unclear. Here, we aimed to explore the function and the underlying mechanism of PKM2 on malignant phenotypes in gastric carcinoma. In this study, the mRNA levels and protein levels of PKM2 in gastric carcinoma cell lines and normal gastric mucosa epithelial cell lines were detected using quantitative real-time PCR and western blot, respectively. PKM2 was downregulated by siRNA transfection. HIF-1α or BCL-6 was upregulated by corresponding overexpression plasmid. Cell viability was detected using CCK-8 assay. Cell invasion and migration were determined using transwell assay. Higher expression of PKM2 was observed in human gastric carcinoma cell lines MKN-45 and SGC-7901 than in the normal gastric mucosa epithelial cell line GES-1. PKM2 knockdown suppressed cancer cell invasion and migration and inhibited the epithelial-mesenchymal transition (EMT) phenotype by inhibiting E-cadherin and promoting vimentin and N-cadherin expression. Also, we observed that PKM2 knockdown suppressed the hypoxia-inducible factor alpha (HIF-1α) and B-cell lymphoma 6 (BCL-6) signaling pathway. HIF-1α overexpression reversed the function of PKM2 silencing on cell invasion, migration, EMT, and BCL-6 expression. BCL-6 overexpression also reversed the function of PKM2 silencing on cell invasion, migration, and EMT but did not affect HIF-1α expression. Taken together, data from our study suggest that PKM2 knockdown impeded cell migration, invasion, and EMT of gastric carcinoma cells via the HIF-1α/BCL-6 pathway.


Asunto(s)
Carcinoma/metabolismo , Proteínas Portadoras/metabolismo , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Proteínas de la Membrana/metabolismo , Neoplasias Gástricas/metabolismo , Hormonas Tiroideas/metabolismo , Cadherinas/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Transición Epitelial-Mesenquimal , Epitelio/metabolismo , Silenciador del Gen , Humanos , Invasividad Neoplásica , Fenotipo , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , ARN Mensajero/metabolismo , Transducción de Señal , Vimentina/metabolismo , Proteínas de Unión a Hormona Tiroide
19.
Front Genet ; 11: 868, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32849839

RESUMEN

Most eukaryotic genes are interrupted by one or more introns, and only prokaryotic genomes are composed of mainly single-exon genes without introns. Due to the absence of introns, intronless genes in eukaryotes have become important materials for comparative genomics and evolutionary biology. There is currently no cohesive database that collects intronless genes in plants into a single database, although many databases on exons and introns exist. In this study, we constructed the Rosaceae Intronless Genes Database (RIGD), a user-friendly web interface to explore and collect information on intronless genes from different plants. Six Rosaceae species, Pyrus bretschneideri, Pyrus communis, Malus domestica, Prunus persica, Prunus mume, and Fragaria vesca, are included in the current release of the RIGD. Sequence data and gene annotation were collected from different databases and integrated. The main purpose of this study is to provide gene sequence data. In addition, attribute analysis, functional annotations, subcellular localization prediction, and GO analysis are reported. The RIGD allows users to browse, search, and download data with ease. Blast and comparative analyses are also provided through this online database, which is available at http://www.rigdb.cn/.

20.
Front Plant Sci ; 11: 1087, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32765567

RESUMEN

BZR transcription factors play essential roles in plant growth and environmental stimuli, and they are also the positive regulators of Brassinosteroid (BR) signal transduction in diverse plants. In addition, BZR TFs, as crucial regulators of BR synthesis, may have multiple stress-resistance functions and their related regulatory mechanisms have been well illustrated in model plants. Here, we carried out a genome-wide identification of BZR members in Chinese pear (Pyrus bretschneideri) and identified 13 members. By comparative analysis in five Rosaceae genomes, BZR members in the pear genome may have undergone large-scale duplication events during evolution. Purifying selection played an important role in almost all of the orthologous and paralogous gene pairs. According to the expression analysis of the PbBZRs during fruit development, three PbBZRs were selected for detailed analysis. Transcriptional activation assays presented that PbBZR1 repressed the promoters of P. bretschneideri lignin biosynthetic genes, such as PbCES9, PbCOMT3, and PbHCT6. Our study traces the evolution of BZR gene family members in Rosaceae genomes and illustrates that the rates of gene loss and gain are far from equilibrium in different species. At the same time, our results suggest that PbBZR1 may be involved in the negative regulation of lignin biosynthesis.

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