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1.
Chemosphere ; 313: 137429, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36462565

RESUMO

Substrate clogging is one of the major operation challenges of subsurface flow constructed wetlands (SSF-CWs). And the phosphorus (P) removal performance and stability of P accumulation of SSF-CWs would be varied with the development of substrate clogging. In this study, three horizontal SSF-CWs microcosms with different clogging degrees were conducted to explore the mechanism of P accumulation behavior influenced by substrate clogging. Increase in clogging degree resulted in hydraulic retention time (HRT) diminution and adsorption sites increase, which jointly led to reduced P removal efficiency at low clogging degree (L-CW), however, higher P removal efficiency was obtained as adsorption sites increase offset HRT diminution at high clogging degree (H-CW). Substrate adsorption was the primary removal pathway in all SSF-CW systems. It accounted for 77.86 ± 2.63% of the P input in the H-CW, significantly higher than the control (60.08 ± 4.79%). This was attributed to a higher proportion of Fe/Al-P accumulated on the substrate of H-CW, since clogging aggravated the anaerobic condition and promoted the generation of Fe ions. The increase in clogging degree also elevated the release risk of the accrued P in SSF-CWs, since Fe/Al-P was considered bioavailable and readily released under environmental disturbance. The obtained results provide new insights into the P transport and transformation in SSF-CWs and would be helpful to optimize substrate clogging management.


Assuntos
Eliminação de Resíduos Líquidos , Áreas Alagadas , Eliminação de Resíduos Líquidos/métodos , Fósforo/metabolismo
2.
Sci Total Environ ; 764: 144293, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33385655

RESUMO

River ecosystems are the most important resource of surface freshwater, but they have frequently been contaminated by excessive nutrient input of nitrogen (N) and phosphorus (P) in particular. An efficient and economic river water treatment technology that possesses the capacity of simultaneous N and P removal is urgently required. In this study, a solar-driven, self-sustainable electrolytic treatment was conducted in situ to intensify N and P removal from eutrophic river water. Solar panel was applied to provide the electrolysis setups with energy (voltage 10 ± 0.5 V), and the current density was controlled to be 0.06 ± 0.02 mA cm-2. Results indicated that the average removal efficiencies of total N (TN) and total P (TP) under electrolysis conditions reached 72.4 ± 11.7 and 13.8 ± 5.3 mg m-2 d-1, which were 3.7- and 4.7-fold higher compared to untreated conditions. Enhanced TN removal mainly reflected the abatement of nitrate N (NO3--N) (80.6 ± 4.1%). The formation of ferric ions through the electro-dissolution of the sacrificial iron anode improved TP removal by coprecipitation with SPS. Combined high-throughput sequencing and statistical analyses revealed that electrolysis significantly reshaped the microbial communities in both the sediment-water interface and suspended sediment (SPS), and hydrogenotrophic denitrifiers (e.g., Hydrogenophaga) were highly enriched under electrolysis conditions. These findings indicated that in situ electrolysis is a feasible and effective technology for intensified nutrient removal from river water.


Assuntos
Microbiota , Eliminação de Resíduos Líquidos , Eletrólise , Água Doce , Nitrogênio , Nutrientes , Fósforo , Rios , Água
3.
J Diabetes Res ; 2019: 8289741, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583252

RESUMO

OBJECTIVE: To investigate the effect of single nucleotide polymorphisms (SNPs) of the key genes in vitamin D metabolic pathway on the serum 25(OH)D level after long-term vitamin D3 supplementation and provide a theoretical basis for rational vitamin D3 supplementation in diabetic patients with different genetic backgrounds. METHODS: Patients with type 2 diabetes (T2DM) who met the inclusive criteria were given 800 IU of vitamin D3 daily for 30 consecutive months. Serum 25(OH)D levels was measured at enrollment and every 6 months after enrollment. The average value of four-time measurements represented individual serum 25(OH)D level during vitamin D3 supplementation. Multiplex TaqMan genotyping was used to determine the distribution of eight candidate SNPs in genes of DHCR7, CYP2R1, CYP27B1, CYP24A1, and VDR, which are key genes in the vitamin D metabolic pathway, in diabetic patients. RESULTS: At baseline, the average serum 25(OH)D level was 22.71 ± 6.87 ng/mL, and 17.9% of patients had a ≥30 ng/mL level. During supplementation, the level of 25(OH)D increased significantly at each time point, and the average 25(OH)D level increased to 30.61 ± 5.04 ng/mL; however, there were 44.6% of patients whose serum 25(OH)D levels were still below 30 ng/mL. In the patients with CYP27B1 (rs10877012) G/T genotype, 71.79% achieved sufficient level of 25(OH)D, which was significantly higher than the other two genotypes (P < 0.05). Compared with those with T/T genotype, the RR of the patients with rs10877012 for <30 ng/mL level was 0.544 (95% CI: 0.291-0.917), and the RR after adjusting age and outdoor activity was 0.560 (95% CI: 0.292-0.970). CONCLUSION: The serum 25(OH)D level in patients with diabetes mellitus after long-term vitamin D3 supplementation is associated with CYP27B1 polymorphism. Patients with rs10877012 G/T allele have a better response to vitamin D3 supplementation. TRIAL REGISTRATION: This trial is registered with ChiCTR-IPC-17012657.


Assuntos
Colecalciferol/uso terapêutico , Diabetes Mellitus Tipo 2/genética , Suplementos Nutricionais , Predisposição Genética para Doença , Deficiência de Vitamina D/genética , Vitamina D/análogos & derivados , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Idoso , Colecalciferol/administração & dosagem , Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D3 24-Hidroxilase/genética
4.
Plant Physiol ; 181(4): 1600-1614, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31548267

RESUMO

RETINOBLASTOMA-RELATED (RBR) is an essential gene in plants, but its molecular function outside of its role in cell cycle entry remains poorly understood. We characterized the functions of OsRBR1 and OsRBR2 in plant growth and development in rice using both forward- and reverse-genetics methods. The two genes were coexpressed and performed redundant roles in vegetative organs but exhibited separate functions in flowers. OsRBR1 was highly expressed in the floral meristem and regulated the expression of floral homeotic genes to ensure floral organ formation. Mutation of OsRBR1 caused loss of floral meristem identity, resulting in the replacement of lodicules, stamens, and the pistil with either a panicle-like structure or whorls of lemma-like organs. OsRBR2 was preferentially expressed in stamens and promoted pollen formation. Mutation of OsRBR2 led to deformed anthers without pollen. Similar to the protein interaction between AtRBR and AtMSI1 that is essential for floral development in Arabidopsis, OsMSI1 was identified as an interaction partner of OsRBR1 and OsRBR2. OsMSI1 was ubiquitously expressed and appears to be essential for development in rice (Oryza sativa), as the mutation of OsMSI1 was lethal. These results suggest that OsRBR1 and OsRBR2 function with OsMSI1 in reproductive development in rice. This work characterizes further functions of RBRs and improves current understanding of specific regulatory pathways of floral specification and pollen formation in rice.


Assuntos
Genes de Plantas , Morfogênese/genética , Oryza/genética , Proteínas de Plantas/genética , Pólen/genética , Retinoblastoma/genética , Sequência de Bases , Regulação da Expressão Gênica de Plantas , Modelos Biológicos , Mutação/genética , Especificidade de Órgãos/genética , Oryza/ultraestrutura , Fenótipo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Pólen/ultraestrutura , Ligação Proteica , Frações Subcelulares/metabolismo
5.
Nutr Cancer ; 71(6): 1030-1039, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038367

RESUMO

Vitamin D as an adjuvant therapy for cancer patients is hoped to have a beneficial outcome based on its physiological activity, but clinical trials so far by addition of vitamin D show unremarkable curative improvement, mechanism for explain this phenomena is not well-understood. The aim of this study was to determine whether vitamin D resists cyclophosphamide (CP)-induced genomic and DNA damage. In CHL cells in vitro, 1α,25-(OH)2D3 at 10, 50, and 100 nM was found to alleviate the frequency of chromosomal aberration with an alleviation range of 40.7-44.0%. There was a dose-dependent decrease for a proportion of γ-H2AX foci positive cells in response to an increase in 1α,25-(OH)2D3 concentration. Two vitamin D3 injections of 1,000, 5,000, or 10,000 IU suppressed CP-induced micronucleus formation in mice BMCs with an alleviation range of 36.7-44.5%, mitigated lymphocytes DNA damage reflected by lower tail DNA, tail length and olive tail moment parameter in comet assay. Vitamin D showed an antagonistic effect on CP-induced genomic and DNA damage. Our data suggest that vitamin D as an adjuvant combine antineoplastic drug with genotoxicity administer to tumor patients is contraindicant.


Assuntos
Aberrações Cromossômicas/efeitos dos fármacos , Ciclofosfamida/farmacologia , Dano ao DNA , Pulmão/patologia , Vitamina D/farmacologia , Animais , Antineoplásicos Alquilantes/farmacologia , Células Cultivadas , Cricetulus , Técnicas In Vitro , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Vitaminas/farmacologia
6.
Medicine (Baltimore) ; 97(52): e13902, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30593205

RESUMO

The aim of this study was first to investigate associations between maternal dietary patterns and autism spectrum disorders (ASDs) and second to investigate association between maternal supplement intake and ASD.We used a case-control study design to enroll typically developing (TD) children and children with ASD, and data were derived from the Autism Clinical and Environmental Database (ACED).Three seventy four children with AUTISM and 354 age matched TD children were included. The multivariate logistic regression model revealed that maternal unbalanced dietary patterns before conception had a significant increased risk of ASD in offspring (mostly meat: adjusted OR, 4.010 [95% CI, 1.080, 14.887]; mostly vegetable: adjusted OR, 2.234 [95% CI, 1.009, 4.946]); maternal supplementation of calcium during pregnancy preparation was associated with decreased ASD risk (adjusted OR, 0.480 [95% CI, 0.276, 0.836]).This study provided preliminary evidence that maternal unbalanced dietary patterns may be a risk factor for ASD and supplementation of calcium during pregnancy preparation may be inversely associated with ASD in offspring.


Assuntos
Transtorno do Espectro Autista/epidemiologia , Dieta/estatística & dados numéricos , Suplementos Nutricionais/estatística & dados numéricos , Mães/estatística & dados numéricos , Adulto , Fatores Etários , Índice de Massa Corporal , Cálcio/administração & dosagem , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Feminino , Ácido Fólico/administração & dosagem , Humanos , Modelos Logísticos , Masculino , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos
7.
Bioresour Technol ; 214: 797-805, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27177713

RESUMO

Dissolved oxygen (DO) is one of the most important factors that can influence pollutants removal in constructed wetlands (CWs). However, problems of insufficient oxygen supply and inappropriate oxygen distribution commonly exist in traditional CWs. Detailed analyses of DO supply and distribution characteristics in different types of CWs were introduced. It can be concluded that atmospheric reaeration (AR) served as the promising point on oxygen intensification. The paper summarized possible optimizations of DO in CWs to improve its decontamination performance. Process (tidal flow, drop aeration, artificial aeration, hybrid systems) and parameter (plant, substrate and operating) optimizations are particularly discussed in detail. Since economic and technical defects are still being cited in current studies, future prospects of oxygen research in CWs terminate this review.


Assuntos
Nitrogênio/química , Oxigênio/química , Fósforo/química , Áreas Alagadas , Adsorção , Atmosfera , Poluentes Ambientais/química , Recuperação e Remediação Ambiental , Gases , Plantas , Águas Residuárias
8.
Int Psychogeriatr ; 28(7): 1191-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26926248

RESUMO

BACKGROUND: Both diabetes and depression have become serious public health problems and are major contributors to the global burden of disease. People with diabetes have been shown to have higher risk of depression. The purpose of this study was to observe the differences in depression between older Chinese adults with known or unknown diabetes. METHODS: Data came from the national baseline survey of China Health and Retirement Longitudinal Study (CHARLS). The Center for Epidemiologic Studies Depression Scale was used to assess depression. Participants with a history of diabetes diagnosis were considered to have known diabetes, and those with newly-diagnosed diabetes were considered to have unknown diabetes. Multiple logistic regression analysis was applied to estimate odds ratio (OR) for depression in predictor variables. RESULTS: Overall, 39.1% of the 2,399 participants with diabetes suffered from depression. The prevalence of depression was significantly higher (p < 0.001) in people with known diabetes (43.5%) than those with unknown diabetes (35.1%). The biggest differences between the two groups were found in the middle aged, in women, in the less educated and in married people. In known diabetes, people treated with traditional Chinese medicine (TCM) coupled with oral western medicine (WM) and/or insulin had two-fold odds of depression compared to those without treatment. CONCLUSION: The knowledge of having diabetes, treatments and suffering from other chronic diseases were associated with the higher prevalence of depression in people with known diabetes compared to those with unknown diabetes. Prevention of depression in diabetics should receive more attention in the middle aged, women and the less education.


Assuntos
Depressão , Diabetes Mellitus , Fatores Etários , Idoso , China/epidemiologia , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/fisiopatologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Aposentadoria/psicologia , Aposentadoria/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos
9.
Molecules ; 19(12): 20906-12, 2014 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-25514229

RESUMO

Radix isatidis (Banlangen), a famous traditional Chinese medicine, has been used for thousands of years in China due to its anti-viral activity. Through our research, we inferred that the anti-viral activity of Radix isatidis depended on the water-soluble part. Among the components of this extract, the isoquinoline derivative 1 was isolated for the first time and has shown better anti-viral activity than other constituents. In this study, to solve the problem of sourcing sufficient quantities of compound 1, a total synthesis route is described, and several analogues are also evaluated for their anti-viral activities. Among them, compound 8 shown potent anti-viral activity with an IC50 value of 15.3 µg/mL. The results suggested that isoquinoline derivatives possessed potent anti-viral activity and are worthy further development.


Assuntos
Antivirais/síntese química , Medicamentos de Ervas Chinesas/química , Isoquinolinas/síntese química , Animais , Antivirais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Herpesvirus Humano 1/efeitos dos fármacos , Concentração Inibidora 50 , Isoquinolinas/farmacologia , Células Vero
10.
J Nutr Biochem ; 21(5): 390-6, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19427779

RESUMO

The aim of this study was to determine whether the extracellular-signal-regulated kinase 1/2 (ERK1/2) pathway is involved in genistein- and equol-induced cell proliferation and estrogen receptor (ER) alpha transactivation. For MCF-7 human breast cells, low concentrations of genistein and equol enhanced proliferation and induced MCF-7 cells to enter the S-phase. Genistein- and equol-induced cell proliferation and S-phase entry were blocked by the ERalpha antagonists 4-hydroxytamoxifen and ICI 182,780 and by the mitogen-activated protein kinase 1/2 inhibitor U0126. These data indicated that ERalpha and mitogen-activated protein extracellular kinase/ERK signaling were required for the effects of genistein/equol on cell growth and cell cycle progression. Genistein and equol induced delayed and prolonged activation of ERK1/2. Inhibition of ERK1/2 phosphorylation by U0126 led to complete suppression of genistein- and equol-induced estrogen response element reporter activity and to suppression of the estrogen-responsive gene pS2. The anti-estrogen ICI had no effect on genistein- and equol-induced ERK1/2 phosphorylation. These results suggest that activation of ERK1/2 lies upstream of ER-mediated transcription, and that ERK1/2 activation is necessary for the transactivation of ERalpha. In conclusion, genistein and equol elicit a delayed activation of ERK1/2, and this activation appears to be involved in the proliferation of breast cancer cells and estrogen-dependent transcriptional activation.


Assuntos
Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Genisteína/farmacologia , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Ativação Transcricional/efeitos dos fármacos , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Equol , Antagonistas de Estrogênios/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Feminino , Genes Reporter , Humanos , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional , Fatores de Tempo
11.
J Anal Toxicol ; 33(9): 588-94, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20040133

RESUMO

A rapid, sensitive, and specific liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) method was developed and validated for simultaneous determination of aconitine (AC), mesaconitine (MA), and hypaconitine (HA), the three toxic constituents from Sini decoction (SND) in rat plasma. After the addition of citalopram as the internal standard (IS), plasma samples were basified with 100 microL 10% ammonium hydroxide, and then extracted with 1 mL ethyl acetate. Chromatographic separation was performed on a CN column (250 mm x 4.6 mm, 5 microm) with a mobile phase of methanol/40 mM ammonium acetate/formic acid (950:45:5, v/v/v) at the flow rate of 1.0 mL/min. Analytes were determined in a triple-quadrupole mass spectrometer in the selected reaction-monitoring (SRM) mode using electrospray source with positive mode. The method was validated over the concentration ranges of 0.01-10 ng/mL for AC, MA, and HA. The variation coefficients were always < 15% for both intraday and interday precision for each analyte. Mean accuracies were also within +/-15%. The method was proved to be sensitive, rapid, specific, accurate, and reproducible. It has been successfully applied to the pharmacokinetics study on rats after oral administration of SND.


Assuntos
Aconitina/análogos & derivados , Aconitina/sangue , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Aconitina/administração & dosagem , Aconitina/farmacocinética , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/normas , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray/normas , Espectrometria de Massas em Tandem/normas
12.
J Steroid Biochem Mol Biol ; 113(3-5): 209-16, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19167497

RESUMO

Despite the wide use of Chinese licorice root (Glycyrrhiza uralensis) for the treatment of menopausal complaints, little is known on its potential estrogenic properties, and available information relative to its effects on cell proliferation is contradictory. In this study, the estrogenic properties of licorice root were evaluated in vitro by use of several assays. The effects of increasing concentrations of a DMSO extract of licorice root on the growth of MCF-7 breast cancer cells were biphasic. The extract showed an ER-dependent growth-promoting effect at low concentrations and an ER-independent anti-proliferative activity at high concentrations. In further experiments, licorice root was sequentially extracted to yield four fractions: hexane, EtOAc, methanol and H(2)O. Only the EtOAc extract had effects on cell proliferation similar to the DMSO extract. The hexane extract had no effect on cell growth. In contrast, the methanol and water extracts showed an ER-independent, growth-promoting effect. Similar to its effects on cell proliferation, the EtOAc extract had a biphasic effect on S phase cell cycle distribution and the level of PCNA protein. This extract-induced transactivation of endogenous ERalpha in MCF-7 cells, supported by inducing down-regulation of ERalpha protein and mRNA levels, and up-regulation of ERalpha target genes pS2 and GREB1. These results suggest that the activity of licorice root and the balance between increased risk for cancer and prevention of estrogen-dependent breast cancer may depend on the amount of dietary intake.


Assuntos
Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Glycyrrhiza uralensis/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios/farmacologia , Feminino , Humanos , Fitoestrógenos/metabolismo , Fitoestrógenos/farmacologia , Extratos Vegetais/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Solventes/química
14.
J Med Chem ; 51(22): 7094-8, 2008 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-18983139

RESUMO

cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine, 4 (A-987306) is a new histamine H(4) antagonist. The compound is potent in H(4) receptor binding assays (rat H(4), K(i) = 3.4 nM, human H(4) K(i) = 5.8 nM) and demonstrated potent functional antagonism in vitro at human, rat, and mouse H(4) receptors in cell-based FLIPR assays. Compound 4 also demonstrated H(4) antagonism in vivo in mice, blocking H(4)-agonist induced scratch responses, and showed anti-inflammatory activity in mice in a peritonitis model. Most interesting was the high potency and efficacy of this compound in blocking pain responses, where it showed an ED(50) of 42 mumol/kg (ip) in a rat post-carrageenan thermal hyperalgesia model of inflammatory pain.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Benzofuranos/farmacologia , Hiperalgesia/tratamento farmacológico , Dor/prevenção & controle , Quinazolinas/farmacologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Benzofuranos/síntese química , Benzofuranos/química , Carragenina , Modelos Animais de Doenças , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Hiperalgesia/induzido quimicamente , Ligantes , Camundongos , Estrutura Molecular , Dor/fisiopatologia , Peritonite/tratamento farmacológico , Quinazolinas/síntese química , Quinazolinas/química , Ratos , Receptores Histamínicos , Receptores Histamínicos H4 , Estereoisomerismo , Relação Estrutura-Atividade
15.
Ai Zheng ; 26(4): 357-60, 2007 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-17430651

RESUMO

BACKGROUND & OBJECTIVE: Nowadays, reversing the multidrug resistance (MDR) of thermotolerant carcinoma cells is a hot topic in tumor thermatology. This study was to investigate the adriamycin (ADR)-resistance of thermotolerant hepatocarcinoma cell line HepG2/thermotolerance and the effect of neferine (Nef) on the ADR-resistance of HepG2/thermotolerance cells. METHODS: Cell proliferation was measured by MTT assay. Cell apoptosis was detected by flow cytometry (FCM) with PI staining. The expression of Bcl-2 was measured by FCM using fluorescein isothiocyanate (FITC)-conjugated anti-bcl-2 antibodies. RESULTS: The proliferation rate and apoptosis rate of HepG2/thermotolerance cells cultured in 43 degrees C for 24 h were (89.6+/-5.4)% and (13.6+/-5.4)%, respectively; however, those of HepG2 cells were (23.9+/-3.6)% and (68.9+/-7.3)%, respectively. The 50% inhibition concentration (IC50) of ADR was 10.8 times higher for HepG2/thermotolerance cells than for HepG2 cells [(113.7+/-12.7) micromol/L vs. (10.5+/-2.3) micromol/L]. When treated with 1, 10, 100 micromol/L ADR at 37 degrees C for 24 h, the apoptosis rates of HepG2/thermotolerance cells were (9.3+/-2.6)%, (17.8+/-7.3)%, and (32.9+/-8.6)%, respectively, but those of HepG2 cells were (14.3+/-3.9)%, (38.9+/-6.8)%, and (62.7+/-5.9)%, respectively. In the presence of 10 and 40 micromol/L Nef, the IC50 of ADR for HepG2/thermotolerance cells was significantly decreased from (113.7+/-12.7) micromol/L to (63.7+/-5.6) micromol/L and (16.8+/-2.8) micromol/L, and the cell apoptosis induced by 10 micromol/L ADR was significantly increased from (17.8+/-4.3)% to (26.8+/-5.9)% and (34.9+/-8.7)%, respectively. Bcl-2 was overexpressed in HepG2/thermotolerance cells, whereas it was down-regulated when the cells were treated with 40 micromol/L Nef for 24 h. CONCLUSIONS: HepG2/thermotolerance cells are ADR-resistant. Nef may reverse the ADR-resistance of HepG2/thermotolerance cells by down-regulating Bcl-2 expression.


Assuntos
Benzilisoquinolinas/farmacologia , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Hipertermia Induzida , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
16.
Bioorg Med Chem Lett ; 12(21): 3055-8, 2002 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-12372500

RESUMO

The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyrrolidine ring was performed using pre-formatted precursor sets, where applicable, to afford several compounds with high affinity and selectivity for the H(3) receptor.


Assuntos
Antagonistas dos Receptores Histamínicos/síntese química , Antagonistas dos Receptores Histamínicos/farmacologia , Pirrolidinas/síntese química , Pirrolidinas/farmacologia , Receptores Histamínicos H3/efeitos dos fármacos , Acilação , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Avaliação Pré-Clínica de Medicamentos , Humanos , Técnicas In Vitro , Ligantes , Ratos , Receptores Histamínicos H1/efeitos dos fármacos , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H2/efeitos dos fármacos , Receptores Histamínicos H2/metabolismo , Relação Estrutura-Atividade
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