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1.
Pharmacol Rep ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965200

RESUMO

Saikosaponin D, a saponin compound, is extracted from Bupleurum and is a principal active component of the plant. It boasts a variety of pharmacologic effects including anti-inflammatory, antioxidant, immunomodulatory, metabolic, and anti-tumor properties, drawing significant attention in anti-tumor research in recent years. Research indicates that saikosaponin D inhibits the proliferation of numerous tumor cells, curbing the progression of cancers such as liver, pancreatic, lung, glioma, ovarian, thyroid, stomach, and breast cancer. Its anti-tumor mechanisms largely involve inhibiting tumor cell proliferation, promoting tumor cell apoptosis, thwarting tumor-cell invasion, and modulating tumor cell autophagy. Moreover, saikosaponin D enhances the sensitivity to anti-tumor drugs and augments body immunity. Given its multi-faceted anti-tumor roles, saikosaponin D offers promising potential in anti-tumor therapy. This paper reviews recent studies on its anti-tumor effects, aiming to furnish new theoretical insights for clinical cancer treatments.

2.
J Agric Food Chem ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607803

RESUMO

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.

3.
Front Oncol ; 14: 1334915, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515577

RESUMO

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.

4.
Ecotoxicol Environ Saf ; 272: 116019, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38295734

RESUMO

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.


Assuntos
Praguicidas , Poluentes do Solo , Humanos , Praguicidas/química , Adsorção , Poluentes do Solo/análise , Carvão Vegetal/química , Solo/química , Biodiversidade
5.
Biomed Pharmacother ; 170: 116097, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38160624

RESUMO

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.


Assuntos
Antineoplásicos , Neoplasias Hepáticas , Ácido Oleanólico , Saponinas , Humanos , Linhagem Celular Tumoral , Qualidade de Vida , Saponinas/farmacologia , Saponinas/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico
6.
Bioorg Med Chem ; 95: 117486, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37847948

RESUMO

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.


Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Resistência a Múltiplos Medicamentos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
7.
Pest Manag Sci ; 79(12): 4784-4794, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37471098

RESUMO

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.


Assuntos
Fungicidas Industriais , Fusarium , Tricotecenos , Triticum , Fungicidas Industriais/farmacologia , Doenças das Plantas/prevenção & controle
8.
Pharmacol Rep ; 75(4): 891-906, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37202657

RESUMO

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.


Assuntos
Neoplasias Pulmonares , Fosfatidilinositol 3-Quinases , Humanos , Proliferação de Células , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo
9.
Sci Total Environ ; 874: 162585, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-36870510

RESUMO

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.


Assuntos
Inseticidas , Estupro , Abelhas , Animais , Malation/toxicidade , Malation/química , Inseticidas/toxicidade , Inseticidas/análise , Proteoma , Cromatografia Líquida , Espectrometria de Massas em Tandem
10.
Molecules ; 28(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36677638

RESUMO

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.


Assuntos
Inseticidas , Resíduos de Praguicidas , Piretrinas , Raphanus , Humanos , Piretrinas/análise , Resíduos de Praguicidas/análise , Medição de Risco , Inseticidas/análise
11.
J Agric Food Chem ; 71(3): 1426-1433, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36630283

RESUMO

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.


Assuntos
Fungicidas Industriais , Poluentes do Solo , Fungicidas Industriais/química , Ecossistema , Estereoisomerismo , Simulação de Acoplamento Molecular , Poluentes do Solo/química , Espectrometria de Massas em Tandem/métodos , Solo/química
12.
Oncol Rep ; 49(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36416347

RESUMO

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.


Assuntos
MicroRNAs , Neoplasias , Humanos , RNA Circular/genética , Fator A de Crescimento do Endotélio Vascular , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Biomarcadores Tumorais
13.
Ecotoxicol Environ Saf ; 241: 113784, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35738101

RESUMO

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.


Assuntos
Fungicidas Industriais , Oryza , Anilidas , Cromatografia Líquida , Fungicidas Industriais/química , Fungicidas Industriais/toxicidade , Pirazóis , Estereoisomerismo , Espectrometria de Massas em Tandem/métodos , Triazóis/química , Triticum
14.
Pest Manag Sci ; 78(7): 3012-3018, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35426212

RESUMO

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.


Assuntos
Citrus , Hemípteros , Inseticidas , Praguicidas , Animais , Abelhas , Cromatografia Líquida , Inseticidas/toxicidade , Praguicidas/análise , Néctar de Plantas , Piridinas , Estereoisomerismo , Espectrometria de Massas em Tandem/métodos
15.
Front Med (Lausanne) ; 9: 1052540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36687445

RESUMO

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.

16.
Pak J Pharm Sci ; 34(3(Special)): 1271-1276, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602399

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Aspergillus fumigatus/metabolismo , Acetatos/química , Acetatos/farmacologia , Animais , Aspergillus fumigatus/química , Bacillus/efeitos dos fármacos , Bacillus licheniformis/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Escherichia coli/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Insetos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Micotoxinas/farmacologia , Fenóis/química , Fenóis/farmacologia , Éteres Fenílicos/química , Éteres Fenílicos/farmacologia , Espectroscopia de Prótons por Ressonância Magnética , Pseudomonas aeruginosa/efeitos dos fármacos , Piranos/química , Piranos/farmacologia , Staphylococcus aureus/efeitos dos fármacos
17.
Pharmacol Res ; 173: 105900, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34547385

RESUMO

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.


Assuntos
Antineoplásicos , Inibidores de Fosfoinositídeo-3 Quinase , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Isoenzimas/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/química , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Proteólise , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/antagonistas & inibidores
18.
Int J Pharm ; 603: 120644, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33964335

RESUMO

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.


Assuntos
Neoplasias da Mama , Grafite , Neoplasias da Mama/tratamento farmacológico , Carbono , Feminino , Humanos
19.
Biomed Res Int ; 2020: 7467104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376737

RESUMO

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.


Assuntos
Carcinoma/metabolismo , Proteínas de Transporte/metabolismo , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Gástricas/metabolismo , Hormônios Tireóideos/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Transição Epitelial-Mesenquimal , Epitélio/metabolismo , Inativação Gênica , Humanos , Invasividade Neoplásica , Fenótipo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Vimentina/metabolismo , Proteínas de Ligação a Hormônio da Tireoide
20.
Front Plant Sci ; 11: 1087, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765567

RESUMO

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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