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1.
Molecules ; 29(13)2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38999168

RESUMEN

Polyoxometalate (POM)-based ionic liquids (POM-ILs) are gaining increasing attention due to their diverse structures and functionalities. POMs in POM-ILs not only act as essential structural building blocks but also play a crucial role in their functional performance. With the incorporation of POMs, POM-ILs find applications in various fields such as chemical catalysis, energy science, materials science, sensors, and more. The abundant availability of POMs and other building blocks in POM-ILs, along with their versatile combination possibilities, present promising opportunities for the future. Rather than focusing solely on discovering new structures of POM-ILs, current developments in this field emphasize exploring their functions, leading to the emergence of numerous new applications. Summarizing these advancements aids in understanding the latest trends and facilitates rapid evolution. This review examines the recent five years' worth of results to analyze the new functions of POM-ILs, categorizing them based on their unique characteristics.

2.
Cancer Biol Ther ; 24(1): 2265055, 2023 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-37831547

RESUMEN

PURPOSE: Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR)-2. This study was conducted to assess the efficacy and safety of apatinib combined with exemestane in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). METHODS: This single-center, single-arm phase II study enrolled patients with ER+/HER2- MBC progressed on previous letrozole or anastrozole. Stratified analysis was performed according to the number of chemotherapy regimens for metastatic disease. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS) and toxicity. Patients received apatinib at a starting dose of 500 mg/d and exemestane 25 mg/d on days 1-28 of each 4-week cycle. RESULTS: Thirty patients were enrolled with median four prior anticancer therapies. Eighty percent of patients received chemotherapy for metastatic disease. The median PFS (mPFS) and OS were 5.6 (95%CI: 4.3-6.9) months and 15.7 (95% CI: 9.7-21.7) months, respectively. The ORR, DCR, and CBR were 21.4%, 71.4%, and 46.4%, respectively. Patients with 0-1 line chemotherapy for MBC showed a slightly longer mPFS compared to those with ≥2 lines chemotherapy (mPFS: 6.4 months vs 4.8 months, P = .090). Most of the AEs were grade 1/2. One patient (3.3%) who suffered bone marrow metastases experienced grade 4 thrombocytopenia, and 14 experienced grade 3 AEs. Fifty percent of patients were given reduced dose for apatinib. CONCLUSIONS: Apatinib plus exemestane exhibited objective efficacy in patients with ER+/HER2- MBC who have failed multiple lines of treatment. The AEs of apatinib required close monitoring and most of patients were well tolerated.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Receptores de Estrógenos/metabolismo , Factor A de Crecimiento Endotelial Vascular
3.
Ying Yong Sheng Tai Xue Bao ; 34(12): 3203-3213, 2023 Dec.
Artículo en Chino | MEDLINE | ID: mdl-38511358

RESUMEN

River water quality is influenced by land use and landscape distribution patterns. Quantifying the relationship between land use, landscape pattern and water quality factor at different riparian buffer zone scales is of great significance for rational land use planning and water quality improvement. Based on water quality data from 91 sites in May 2021 in the Gaya River Basin, we analyzed the spatial characteristics of land use types and landscape patterns at the riparian buffer zone scales. With redundancy analysis (RDA) and generalized additive models (GAM), we examined the effects of land use and landscape patterns on river water quality. The results showed that water quality was primarily impacted by total nitrogen (TN). Farmland was the dominant land use type at riparian buffer zone of 50, 100 and 500 m. The sampling sites were classified into farmland dominant group and farmland other group. Forest was dominant at riparian buffer zone of 1000, 1500, 2000 m, and the sampling sites were classified into forest dominant group and forest other group. 100 m riparian buffer zone was the strongest scale in the Gaya River, and 1000 m was the second. Land use types in the forest dominant group were closely related with electrical conductivity, dissolved oxygen, phosphate, permanganate index and ammonium (NH4+-N) of water. NH4+-N was positively correlated with proportion of forest and farmland area. Phosphate was significantly affected by Shannon diversity index (SHDI). SHDI and largest patch index (LPI) was the key landscape indices affecting permanganate index. TN was significantly impacted by area proportion of forest, grassland and LPI in farmland dominant group, showing decreasing trend with the area proportion of forest increasing from 8% to 40%. Total suspended solids in farmland other group were significantly correlated with proportion of farmland area, while negatively correlated with proportion of forest area. Water quality in the Gaya River was mainly affected by proportion of forest area, followed by proportion of farmland area. The combined effects of LPI, SHDI and other land use types played an important role in affecting water quality.


Asunto(s)
Compuestos de Manganeso , Óxidos , Ríos , Calidad del Agua , Monitoreo del Ambiente/métodos , China , Fosfatos , Nitrógeno/análisis
4.
Ann Palliat Med ; 10(12): 12101-12112, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35016411

RESUMEN

BACKGROUND: This study aimed to prospectively evaluate and investigate the efficacy and safety of recombinant human endostatin (Rh-endostatin) combined with platinum-based regimens for advanced triple-negative breast cancer (TNBC) patients. METHODS: This study was a prospective, single-arm, single-center, open-label trial. From January 2017 to August 2019, 21 women aged 18-70 years with histologically confirmed advanced TNBC were enrolled. Rh-endostatin at 30 mg/d was continuously pumped for 7 days and used synchronously with the chemotherapy cycle. The primary endpoint of this study was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), and toxicity. RESULTS: The median PFS (mPFS) was 8.8 months (95% CI: 7.2-10.4 months), and the median OS was 13.3 months (95% CI: 11.6-15.0 months). The ORR and CBR for the whole population were 47.6% and 52.4%, respectively. Patients sensitive to anthracycline and taxane drugs showed a significantly longer mPFS compared to those who were resistant to anthracycline and taxane drugs (mPFS: 8.8 vs. 5.3 months, P=0.038). For patients who received first- and second-line therapy or beyond, the mPFS was 8.8 and 5.3 months, respectively, with a significant difference (P=0.025). No statistically significant differences in the mPFS between pemetrexed combined with platinum and gemcitabine/taxanes combined with platinum were observed. The most common grade 3-4 hematologic toxicities were neutropenia (14.3%) and anemia (14.3%). One patient (4.8%) experienced febrile neutropenia. No grade 3-4 non-hematologic toxicities were observed, and no treatment-related deaths were reported in this study. CONCLUSIONS: This study revealed that Rh-endostatin might enhance the antitumor effects of platinum-based chemotherapy for advanced TNBC patients with well-tolerated toxicities, which may provide a new basis and novel idea for the treatment of TNBC. However, further investigations and validation of its long-term efficacy and toxicity are warranted in the future.


Asunto(s)
Endostatinas , Neoplasias de la Mama Triple Negativas , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Endostatinas/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Platino (Metal)/uso terapéutico , Estudios Prospectivos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto Joven
5.
Aging (Albany NY) ; 13(1): 619-645, 2020 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-33281116

RESUMEN

Evidences shows that immune and stroma related genes in the tumour microenvironment (TME) play a key regulator in the prognosis of Osteosarcomas (OSs). The purpose of this study was to develop a TME-related risk model for assessing the prognosis of OSs. 82 OSs cases aged ≤25 years from TARGET were divided into two groups according to the immune/stromal scores that were analyzed by the Estimate algorithm. The differentially expressed genes (DEGs) between the two groups were analyzed and 122 DEGs were revealed. Finally, three genes (COCH, MYOM2 and PDE1B) with the minimum AIC value were derived from 122 DEGs by multivariate cox analysis. The three-gene risk model (3-GRM) could distinguish patients with high risk from the training (TARGET) and validation (GSE21257) cohort. Furthermore, a nomogram model included 3-GRM score and clinical features were developed, with the AUC values in predicting 1, 3 and 5-year survival were 0.971, 0.853 and 0.818, respectively. In addition, in the high 3-GRM score group, the enrichment degrees of infiltrating immune cells were significantly lower and immune-related pathways were markedly suppressed. In summary, this model may be used as a marker to predict survival for OSs patients in adolescent and young adults.


Asunto(s)
Neoplasias Óseas/genética , Osteosarcoma/genética , Microambiente Tumoral/genética , Adolescente , Neoplasias Óseas/inmunología , Conectina/genética , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 1/genética , Proteínas de la Matriz Extracelular/genética , Femenino , Ontología de Genes , Humanos , Masculino , Osteosarcoma/inmunología , Modelos de Riesgos Proporcionales , Medición de Riesgo , Tasa de Supervivencia , Transcriptoma , Microambiente Tumoral/inmunología , Adulto Joven
6.
Front Plant Sci ; 11: 561903, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33193488

RESUMEN

Melatonin, widely found in various plants as a new antioxidant, could protect plants from various biotic and/or abiotic stresses, including salt stress. MzASMT 1 (KJ123721), a gene from Malus zumi Mats, is a key enzyme required for melatonin synthesis. However, whether the overexpression of MzASMT 1 could regulate the synthesis of melatonin and improve the salt tolerance in tobacco remains unknown. In this study, the overexpression of MzASMT 1 in tobacco increased the melatonin content, and the transgenic lines owned higher salt tolerance capacity. The transgenic lines overexpressing MzASMT 1 exhibited lower degree of leaf wilting; much more fresh weight; higher plant height; longer root; higher relative water content (RWC) of leaves, stem, and root; and higher chlorophyll content and Fv/Fm, which makes transgenic lines better adapt to salt stress. The transgenic lines also had higher accumulation of proline, lower accumulation of malondialdehyde (MDA), and improved antioxidant systems, which protected plants from cell damage and oxidative stress due to excess reactive oxygen species (ROS) accumulation under salt treatment. The transcription of salt response genes was much more highly activated in transgenic lines than in wild type under salt stress. The above results contributed to the understanding of functions for MzASMT 1 in tobacco under salt stress and provided a new choice for the application of MzASMT 1 in improving plant salt tolerance.

7.
J Photochem Photobiol B ; 207: 111882, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32361282

RESUMEN

Silver sulfide­magnesium oxide/graphene oxide (Ag2S-MgO/GO) nanocomposite was prepared via sol-gel/ultrasound method to modify the photo-degradation performance for rhodamine B decontamination under visible and UV light. Analytical studies were performed to distinguish the properties such as structure, morphology, and elements of prepared materials. The average crystallite size of MgO, Ag2S-MgO and Ag2S-MgO/GO is distinguished to be 24.2, 29.3 and 33.1 nm, respectively. The Band gap MgO, Ag2S-MgO and Ag2S-MgO/GO is 4.08, 3.25 and 2.82 eV, respectively. Ag2S-MgO/GO nanocomposites illustrated the highest photo-degradation rate of rhodamine B (RhB) under UV light (98.8%) and visible light (64.8%) during in 60 min. In this project, the process parameter of pH and time were investigated for RhB degradation activity influence. The suggested mechanisms for the enhanced photo-degradation of RhB by Ag2S-MgO/GO nanocomposites under light irradiation due to enhanced charge transfer efficiency via decreasing band gap amount; reduced e-/h+ recombination of MgO with the Ag2S crystal and an enhanced removal efficiency with the supported on graphene oxide. Examination of the antibacterial and antifungal properties of the prepared nano-materials were conducted with Bacillus vallismortis, Escherichia coli, Aspergillus flavus and Trichoderma viride. The beneficial antibacterial and antifungal performance of the Ag2S-MgO/GO nanocomposites was further tested by a great reduction in the number of bacteria and fungi medium with the addition of the Ag2S-MgO/GO nanocomposites.


Asunto(s)
Antiinfecciosos/química , Grafito/química , Óxido de Magnesio/química , Nanocompuestos/química , Compuestos de Plata/química , Bacillus/efectos de los fármacos , Catálisis , Escherichia coli/efectos de los fármacos , Luz , Procesos Fotoquímicos , Rodaminas/química , Relación Estructura-Actividad , Propiedades de Superficie , Factores de Tiempo
8.
Onco Targets Ther ; 13: 1461-1470, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32110044

RESUMEN

BACKGROUND: The fat mass and obesity-associated protein (FTO) was identified as a critical demethylase involved in regulating cellular mRNA stability by removing N6-methyladenosine (m6A) residues from mRNA. Emerging evidence has revealed that FTO is deeply implicated in lung cancer. However, knowledge of the function of FTO in lung adenocarcinoma (LUAC) is limited. METHODS: FTO and FTO R96Q (R96Q), an FTO missense mutant lacking demethylase activity, were ectopically overexpressed, and FTO was knocked down via siRNA in A549 and H1299 cells. The relationships between FTO with cell characteristics and mRNA m6A levels were explored. Furthermore, RNA sequencing was performed on A549 cells. RESULTS: FTO overexpression enhanced the proliferation, migration, and invasion ability of A549 and H1299 cells, decreased mRNA m6A levels. Interestingly, overexpression of R96Q, blunted the effects of FTO overexpression on cell proliferation and invasion. Through RNA sequencing analysis of A549 cells overexpressing FTO or R96Q and control A594 cells, 45 genes were identified as affected by m6A mRNA demethylation. Most of these genes were related to lung cancer, such as laminin γ2, thrombospondin 1, nerve growth factor inducible, integrin alpha11, and proprotein convertase subtilisin/kexin type 9. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that these genes are fundamental to cancer development processes, such as cell migration and extracellular matrix organization. CONCLUSION: Our research shows that FTO facilitates LUAC cell progression by activating cell migration through m6A demethylation; however, further research on the mechanism underlying FTO activity in LUAC is necessary.

9.
Onco Targets Ther ; 13: 1059-1072, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32099408

RESUMEN

OBJECTIVE: To investigate the correlation between the ERCC1 and XPF expression and the clinicopathological parameters of hepatocellular carcinoma (HCC) patients through assessment of the expression of the DNA repair genes ERCC1 and XPF. METHODS: ERCC1 and XPF mRNA expression in HCC (n= 177) and adjacent para-cancer tissues (n=21) were assessed by RT-PCR. The correlation between ERCC1 and XPF expression, clinicopathological features and HCC prognosis were compared. RESULTS: ERCC1 expression in liver cancer tissues was significantly lower than that of adjacent tissues (9.5% (2/21) vs 38.1% (8/21); P<0.05). The positive expression rates of XPF in liver cancer tissues was lower than that of adjacent tissues (14.3% (3/21) vs 71.4% (15/21); P<0.05). ERCC1 and XPF expression were associated with hepatic capsular invasion and microvascular invasion. HCC patients with hepatic capsular invasion and microvascular tumor embolus formation had significantly lower levels of ERCC1 and XPF mRNA than those without hepatic capsular invasion and microvascular tumor embolus formation (P<0.05). In addition, ERCC1 expression was associated with TNM staging of HCC. The expression of ERCC1 mRNA in patients with stage II and III HCC were lower than that of patients with stage I HCC (P<0.05). The low levels of ERCC1 and XPF mRNA significantly correlated with relapse-free survival times (RFS) in HCC patients. The median RFS of the low ERCC1 expression group and low XPF expression group were shorter than those of the high expression group (15.0 months vs 32.0 months, P<0.05) and (19.0 months vs 33.0 months, P<0.05). The decrease in XPF mRNA expression was significantly associated with the overall survival (OS) of HCC patients. The median OS in the low XPF expression group was shorter than that of the high expression group (46.0 months vs 78.0 months, P<0.05). However, no significant difference in OS between the low ERCC1 expression group and the high ERCC1 expression groups were observed (63.0 months vs 64.0 months, P>0.05). Multivariate analysis showed that tumor size and the extent of differentiation were independent factors affecting the RFS in HCC patients (P<0.05). The extent of differentiation and XPF were independent factors affecting the OS in HCC (P<0.05). CONCLUSION: The expression in ERCC1 and XPF were low in HCC and associated with early relapse after HCC surgery. Low XPF expression may be a potential indicator of a high risk of death.

10.
Bioorg Med Chem ; 27(23): 115150, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31635893

RESUMEN

A concept, natural products derivatization method (NPDM), was introduced to assess the influence of natural products on the discovery of targeted anticancer agents. Subsequently, 106 new molecular entities (NMEs) for targeted anticancer agents from 2000 to 2018 were categorized and sorted into four types: ND (Natural Product Derivative), SND (Synthetic Natural Derived), B (Biological Macromolecule), S (Totally synthetic in origin). Furthermore, by setting molecular targeted agents (MTA), cellular targeted agents (CTA), vascular targeted agents (VTA) and immuno targeted agents (ITA) as study subject, ND category and SND category were reviewed from aspects including natural products source, action mechanism and their share in all NMEs in order to comprehensively evaluate the significance of NPDM in the design and development of targeted anticancer agents, and the prospects of this method was also put forward.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Productos Biológicos/química , Productos Biológicos/farmacología , Diseño de Fármacos , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/uso terapéutico , Productos Biológicos/uso terapéutico , Descubrimiento de Drogas/métodos , Humanos , Terapia Molecular Dirigida/métodos , Neoplasias/metabolismo
11.
ACS Omega ; 4(13): 15742-15753, 2019 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-31572878

RESUMEN

Novel 1H-purin-6(9H)-one (D) and 3H-imidazo[4,5-d][1,2,3]trazin-4(7H)-one (E) derivatives were designed, synthesized, and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry spectra. Their herbicidal activity bioassay showed that compound 7d exhibited relatively good activity with 70.4% inhibition rate against Amaranthus retroflexus in postemergence treatments at 1500 g/ha. Antitumor activity indicated that most of the title compounds displayed potent antitumor activity at 20 µM, among all of the promising compounds possessing lower IC50 values than that of temozolomide, compound 7i demonstrated highest activity inhibiting both HepG-2 and U-118 MG cell lines with IC50 values of 2.0 and 3.8 µM, respectively. The structure-activity relationship analysis revealed that introduction of halogen atoms, a bulky bridging bond between benzene ring and nitrogen atom, longer R2 substituents could contribute to the improvement of antitumor activity. Analysis suggested that compound 7i might have potential as new highly active antitumor agent. Overall, D series had better anticancer activities than E series derivatives.

12.
Sci Rep ; 9(1): 11150, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31371772

RESUMEN

Colored-leaf plants are increasingly popular and have been attracting more and more attentions. However, the molecular mechanism of leaf coloration in plants has not been fully understood. In this study, a colored-leaf cultivar of Populus deltoides (Caihong poplar, CHP) and green-leaf cultivar of Populus deltoides L2025 were used to explore the mechanism of leaf coloration through physiological and the whole genome resequencing analysis. The content of anthocyanins, total Chl, and carotenoids in the leaves of CHP and L2025 were evaluated. The ratio of anthocyanins to total Chl in CHP was 25.0 times higher than that in L2025; this could be attributed to the red leaf color of CHP. Based on the whole genome resequencing analysis, 951,421 polymorphic SNPs and 221,907 indels were screened between CHP and L2025. Using qRT-PCR analysis, three structural genes (flavonol synthase 1 family protein, UDP-glucose flavonoid 3-O-glucosyltransferase 3' and flavonoid 3-O-galactosyl transferase family protein) and six transcription factors (MYB-related protein Myb4, transcription factor GAMYB, PtrMYB179, transcription factor bHLH53, transcription factor bHLH3, VARICOSE family protein) may be involved in the anthocyanin synthesis pathway, which could be used as candidate genes to explore the molecular regulation mechanism of leaf coloration in Populus deltoids, and could be used in molecular breeding in the future.


Asunto(s)
Genómica , Populus/genética , Antocianinas/análisis , Antocianinas/biosíntesis , Antocianinas/genética , Carotenoides/análisis , Color , Regulación de la Expresión Génica de las Plantas , Genes de Plantas/genética , Variación Genética , Genoma de Planta/genética , Pigmentación/genética , Hojas de la Planta/química , Hojas de la Planta/genética
13.
Int J Biol Markers ; 32(2): e195-e201, 2017 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-28009434

RESUMEN

BACKGROUND: The Toll-like receptor plays an essential role in controlling immunity and inflammation. This study was to investigate the relationships of genetic variants in TLR2 and TLR3 with hepatitis B virus (HBV) natural clearance and HBV-related hepatocellular carcinoma (HCC) risk in a Chinese male population. METHODS: We analyzed 5 polymorphisms of TLR2 (rs3804099 and rs3804100) and TLR3 (rs5743305, rs3775296 and rs3775291) in a population consisting of 686 participants with HBV natural clearance, 293 chronic HBV carriers and 395 HBV-positive HCC patients, using the improved multiplex ligase detection reaction method. RESULTS: After adjustment for age and smoking and drinking status, no associations were observed either between the 5 single-nucleotide polymorphisms (SNPs) and the HBV natural clearance participants, or between the 5 SNPs and HCC patients. Whereas the stratified analysis showed that under the dominant models, nondrinkers with TLR2 rs3804100 and participants younger than 40 years old with TLR3 rs3775291 were significantly associated with HCC risk when compared with persistent HBV carriers (adjusted odd ratio [OR] = 0.49, 95% confidence interval [95% CI], 0.31-0.78, p = 0.003; and adjusted OR = 0.50, 95% CI, 0.29-0.86, p = 0.013, respectively). Furthermore, the TTTCT haplotype was found to promote the progress of HBV clearance and inhibit development of HBV-related HCC (OR = 0.77, 95% CI, 0.61-0.97, p = 0.029; and OR = 0.72, 95% CI, 0.55-0.94, p = 0.016, respectively). And the CCACC and CCTCT haplotypes were observed to decrease susceptibility to HCC (OR = 0.64, 95% CI, 0.40-1.00, p = 0.048; and OR = 0.43, 95% CI, 0.28-0.68, p<0.001, respectively). CONCLUSIONS: This study revealed that TLR2 rs3804100 and TLR3 rs3775291 polymorphisms may be protective factors for HBV-related HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Receptor Toll-Like 2/genética , Receptor Toll-Like 3/genética , Adulto , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , China , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/genética , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Polimorfismo de Nucleótido Simple
14.
Eur J Med Chem ; 117: 167-78, 2016 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-27092414

RESUMEN

A series of novel carboxamide compounds 19a-19j, 20a-20j and 22a-22d containing piperazine and arylsulfonyl moieties have been synthesized. The bioassay results showed that some compounds exhibited favorable herbicidal activities against dicotyledonous plants and many of them possessed excellent antifungal activities. Among 24 novel compounds, some showed superiority over the commercial fungicides Chlorothalonil, Dimethomorph, Thiophanate-methyl, Iprodione, and Zhongshengmycin at 500 mg/L concentration. Some compounds also exhibited high KARI inhibitory activity at 100 µg/mL concentration and could be used as new KARI lead inhibitors for further studies. Moreover, SAR of these new compounds were comprehensively investigated using different computational methods in which 3D-QSAR model obtained provided useful information for further structural optimization for the discovery of new fungicides. The results of this research will contribute to explore comprehensive biological activities of piperazine-containing compounds in different areas of chemistry.


Asunto(s)
Amidas/síntesis química , Antifúngicos/síntesis química , Herbicidas/síntesis química , Relación Estructura-Actividad Cuantitativa , Amidas/farmacología , Antifúngicos/farmacología , Ácidos Arilsulfónicos/química , Herbicidas/farmacología , Piperazina , Piperazinas/química
15.
Oncol Rep ; 32(5): 1905-12, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25175062

RESUMEN

Radiotherapy has long been considered as the mainstay of treatment for nasopharyngeal carcinoma (NPC). However, locoregional recurrence or distant metastasis may occur in some patients due to the radiation resistance of cancer cells. Autophagy plays a vital role in protecting cells against radiation. However, the mechanism of autophagy in radiation therapy remains obscure. In the present study, we demonstrated that suppression of autophagy related 5 (Atg5) aggravated ionizing radiation (IR)-induced DNA damage and apoptosis in human NPC cells without accelerating the cell cycle, whereas regulation of the cell cycle has been widely regarded as the most important determinant of IR sensitivity. Further study showed that inhibition of autophagy suppressed the mRNA expression of Rad51, a key protein of homologous recombination that has been demonstrated to play a critical role in the repair of DNA double-strand breaks induced by radiation. Moreover, suppression of Atg5 had no impact on the radiosensitivity when cells were pre-treated by the Rad51 inhibitor, and the enhanced radiosensitivity by Atg5 suppression was reversed by overexpression of Rad51 in human NPC cells. Our results suggest that inhibition of autophagy enhances the susceptibility of NPC cells to radiation by reducing Rad51 expression. Therefore, Rad51 targeted therapy may be investigated as a potential novel agent for the adjuvant treatment of traditional radiation of NPC.


Asunto(s)
Proteínas Asociadas a Microtúbulos/genética , Neoplasias Nasofaríngeas/radioterapia , Recombinasa Rad51/genética , Tolerancia a Radiación , Autofagia/efectos de los fármacos , Proteína 5 Relacionada con la Autofagia , Carcinoma , Línea Celular Tumoral , ADN/efectos de la radiación , Daño del ADN , Humanos , Proteínas Asociadas a Microtúbulos/metabolismo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , ARN Interferente Pequeño/metabolismo
16.
Org Biomol Chem ; 12(29): 5427-34, 2014 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-24935054

RESUMEN

Carboxylic acid amide (CAA) fungicides are an important class of agricultural fungicide with oomycete activity and low toxicity toward mammalian cells. To find CAA analogues with high activity against resistant pathogens, a series of substituted N-benzhydryl valinamide carbamate derivatives were designed and synthesized by introducing substituted aromatic rings into valinamide carbamate leads. Bioassays showed that some title compounds exhibited very good in vitro fungicidal activity against Phytophthora capsici and in vivo fungicidal activities against Pseudoperonospora cubensis. Topomer CoMFA was performed to explore the structure-activity relationship on the basis of the in vitro data. The dimethoxy substituted aromatic analogue 9e was found to display higher in vitro fungicidal activity against Phytophthora capsici than iprovalicarb but lower activity than mandipropamid, and higher in vivo fungicidal activity against Pseudoperonospora cubensis than dimethomorph at a dosage of 6.25 µg mL(-1).


Asunto(s)
Amidas/síntesis química , Carbamatos/síntesis química , Carbamatos/farmacología , Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/farmacología , Diseño de Fármacos , Fungicidas Industriales/síntesis química , Amidas/química , Amidas/farmacología , Carbamatos/química , Ácidos Carboxílicos/química , Hongos/efectos de los fármacos , Fungicidas Industriales/química , Fungicidas Industriales/farmacología , Pruebas de Sensibilidad Microbiana , Modelos Moleculares
17.
Funct Integr Genomics ; 13(1): 75-98, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23184474

RESUMEN

R2R3-MYB, bHLH, and WD40 proteins have been shown to control multiple enzymatic steps in the biosynthetic pathway responsible for the production of flavonoids, important secondary metabolites in Camellia sinensis. Few related transcription factor genes have been documented. The presence of R2R3-MYB, bHLH, and WD40 were statistically and bioinformatically analyzed on 127,094 C. sinensis transcriptome unigenes, resulting in identification of 73, 49, and 134 genes, respectively. C. sinensis phylogenetic trees were constructed for R2R3-MYB and bHLH proteins using previous Arabidopsis data and further divided into 27 subgroups (Sg) and 32 subfamilies. Motifs in some R2R3-MYB subgroups were redefined. Furthermore, Sg26 and Sg27 were expanded compared to Arabidopsis data, and bHLH proteins in C. sinensis were grouped into nine subfamilies. According to the functional annotation of Arabidopsis, flavonoid biosynthesis in C. sinensis was predicted to include R2R3-MYB genes in Sg4 (6), Sg5 (2), and Sg7 (1), as well as bHLH genes in subfamily 2 (2) and subfamily 24 (5). The wide evolutionary gap prevented phylogenetic analysis of WD40s; however, a single gene, CsWD40-1, was observed to share 80.4 % sequence homogeny with AtTTG1. Analysis of CsMYB4-1, CsMYB4-2, CsMYB4-3, CsMYB4-4, CsMYB5-1, and CsMYB5-2 revealed the interaction motif [DE]Lx2[RK]x3Lx6Lx3R, potentially contributing to the specificity of the bHLH partner in the stable MYB-bHLH complex. Full-length end-to-end polymerase chain reaction (PCR) and quantitative reverse transcriptase (qRT)-PCR were used to validate selected genes and generate relative expression ratio profiles in C. sinensis leaves by developmental stage and treatment conditions, including hormone and wound treatments. Potential target binding sites were predicted.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Camellia sinensis/genética , Flavonoides/biosíntesis , Proteínas de Plantas/genética , Factores de Transcripción/genética , Secuencia de Aminoácidos , Camellia sinensis/clasificación , Camellia sinensis/metabolismo , Evolución Molecular , Flavonoides/genética , Genes de Plantas , Datos de Secuencia Molecular , Filogenia , Proteínas de Plantas/metabolismo , Factores de Transcripción/metabolismo
18.
BMC Med ; 9: 106, 2011 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-21929825

RESUMEN

BACKGROUND: Increases in human telomerase reverse transcriptase (TERT) expression and telomerase activity are frequently seen in nasopharyngeal carcinoma (NPC). Recently, a variable tandem-repeats polymorphism, MNS16A, located in the downstream region of the TERT gene, was identified and reported to have an effect on TERT expression and telomerase activity. We examined whether the functional MNS16A was related to the risk of occurrence or progression of NPC in the Chinese population. METHODS: We genotyped the MNS16A polymorphism in a case-control study of 855 patients with NPC and 1036 cancer-free controls using PCR, and determined genotype by classifying the DNA band of 243 or 272 base pairs (bp) as the short (S) allele and 302 or 333 bp as the long (L) allele. The genetic associations with the risk of NPC were analyzed by logistic regression. RESULTS: The MNS16A genotype was not associated with the progression of NPC. However, individuals carrying the S alleles (SL + SS genotype) had a significantly reduced risk of NPC occurrence compared with those carrying the LL genotype (odds ratio (OR) = 0. 71, 95% confidence interval (CI) = 0. 52 to 0. 96, P = 0. 025). Using a immunohistochemical assay on the NPC tissues, the SL genotype carriers were found to have lower TERT expression than the LL genotype carriers (P = 0. 035). CONCLUSIONS: Our study indicates that the TERT MNS16A polymorphism may contribute to the risk of NPC onset in Chinese population.


Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias Nasofaríngeas/genética , Polimorfismo Genético , Secuencias Repetidas en Tándem , Telomerasa/genética , Adulto , Carcinoma , Estudios de Casos y Controles , China , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo
19.
Chem Biol Drug Des ; 78(1): 101-11, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21457472

RESUMEN

A series of isosteric analogs of mandipropamid were designed and synthesized via 'click chemistry'. The amide bond of mandipropamid was substituted by a 1,2,3-triazole functional group. The bioassay results have indicated that some of the title compounds exhibited moderate fungicidal activity against Pseudoperonospora cubensis, and the activity has been systematically studied as a function of molecular structure. The low activity of the mandipropamid analog that contains a lipid chain is likely due to the presence of a weak hydrogen bond donor in the 1,2,3-triazole. Furthermore, we have performed the molecular modeling and found that N-methylamide could be more effective than amide as the surrogates to 1,2,3-triazole, which ultimately leads to a longer distance (1.1 Å longer) between the two substitutes in the 1,4-disubstituted 1,2,3-triazole compound.


Asunto(s)
Amidas/síntesis química , Amidas/farmacología , Antifúngicos/síntesis química , Antifúngicos/farmacología , Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/farmacología , Oomicetos/efectos de los fármacos , Amidas/química , Ácidos Carboxílicos/química , Espectroscopía de Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray , Relación Estructura-Actividad
20.
PLoS One ; 6(2): e16748, 2011 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-21304814

RESUMEN

BACKGROUND: Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5, also called as survivin) is a member of the inhibitor of apoptosis protein (IAP) family, which plays an important role in the occurrence and progression of cancer. Recently, a polymorphism in the promoter of BIRC5, -31C/G (rs9904341), was shown to influence BIRC5 expression. METHODS: We examined whether the -31C/G was related to the risk of developing nasopharyngeal carcinoma (NPC) in a case-control population from Guangxi province in southern China, which consists of 855 patients with NPC and 1036 controls. This polymorphism was genotyped by TaqMan assay. The genetic associations with the occurrence and progression of NPC were estimated by logistic regression. RESULTS: We observed a statistically significant increased occurrence of NPC associated with the CC genotype (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.13-1.73; P=0.0020) compared with the genotypes containing G allele (CG + GG genotype). However, no significant association was observed for the -31C/G with the severity of NPC (as measured by tumor-node-metastasis staging system). CONCLUSION: Our findings suggest that the functional polymorphism -31C/G in the promoter of BIRC5 gene may play a role in mediating the susceptibility to NPC among Chinese.


Asunto(s)
Pueblo Asiatico/genética , Proteínas Inhibidoras de la Apoptosis/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Adulto , Carcinoma , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/etnología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Metástasis de la Neoplasia , Polimorfismo de Nucleótido Simple/fisiología , Factores de Riesgo , Survivin
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