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1.
Small ; : e2400541, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644221

RESUMO

The high crystalline covalent triazine framework-1 (CTF-1), composed of alternating triazine and phenylene, has emerged as an efficient photocatalyst for solar-driven hydrogen evolution reaction (HER). However, it is of great challenge to further improve photocatalytic HER performance via increasing crystallinity due to its near-perfect crystallization. Herein, an alternative strategy of scaffold functionalization is employed to optimize the energy band structure of crystalline CTF-1 for boosting hydrogen-evolving activity. Guided by the computational predictions, versatile CTF-based polymer photocatalysts are prepared with different functional groups (OH, NH2, COOH) using binary polymerization for practical hydrogen production. Experiment evidence verifies that the introduction of a limited number of electron-donating groups is sufficient to maintain high crystallinity in CTF, modulate the band structure, broaden visible light absorption, and consequently enhance its photophysical properties. Notably, the functionalization with OH exhibits the most positive effect on CTF-1, delivering a photocatalytic activity with a hydrogen-producing rate exceeding 100 µmol h-1.

2.
Acta Pharm Sin B ; 13(3): 1326-1336, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36970201

RESUMO

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.

3.
Biomed Pharmacother ; 134: 111160, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33370630

RESUMO

Natural products are an important source of new drugs. Some of them may be used directly in clinical settings without further structural modification. One of these directly used natural products is puerarin (Pue), which protects cardiomyocytes against oxidative stress and high glucose stress. Although Pue has been used in clinics for many years, its direct binding targets involved in the protection of cardiomyocytes are not yet fully understood. Here, we reported that Pue could prevent cardiomyocytes from apoptosis under H2O2 and high glucose conditions. Based on affinity-based protein profiling methods, we synthesized an active Pue probe (Pue-DA) with a photosensitive crosslinker to initiate a biological orthogonal reaction. Because of the steric hindrance of Pue-DA, two conformational isomers (syn and anti) unequivocally existed in the probe, and these transformed into one isomer when the probe was heated at 60 °C. We confirmed that the alkylation was on the 7-position phenol group of Pue. Mass spectroscopy revealed that Pue-DA can bind with three proteins, namely CHAF1B, UBE2C, and UBE2T. Finally, cellular thermal shift assay showed that Pue has the ability to stabilize CHAF1B stabilization. The knock-down of CHAF1B reduced the protective effect of Pue on cardiomyocytes. In conclusion, Pue protects cardiomyocytes from apoptosis through binding with CHAF1B.


Assuntos
Antioxidantes/farmacologia , Fator 1 de Modelagem da Cromatina/metabolismo , Isoflavonas/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Apoptose/efeitos dos fármacos , Linhagem Celular , Fator 1 de Modelagem da Cromatina/genética , Glucose/toxicidade , Humanos , Peróxido de Hidrogênio/toxicidade , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Transdução de Sinais , Enzimas de Conjugação de Ubiquitina/metabolismo
4.
Adv Mater ; 32(28): e1907296, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32483883

RESUMO

With the ambition of solving the challenges of the shortage of fossil fuels and their associated environmental pollution, visible-light-driven splitting of water into hydrogen and oxygen using semiconductor photocatalysts has emerged as a promising technology to provide environmentally friendly energy vectors. Among the current library of developed photocatalysts, organic conjugated polymers present unique advantages of sufficient light-absorption efficiency, excellent stability, tunable electronic properties, and economic applicability. As a class of rising photocatalysts, organic conjugated polymers offer high flexibility in tuning the framework of the backbone and porosity to fulfill the requirements for photocatalytic applications. In the past decade, significant progress has been made in visible-light-driven water splitting employing organic conjugated polymers. The recent development of the structural design principles of organic conjugated polymers (including linear, crosslinked, and supramolecular self-assembled polymers) toward efficient photocatalytic hydrogen evolution, oxygen evolution, and overall water splitting is described, thus providing a comprehensive reference for the field. Finally, current challenges and perspectives are also discussed.

5.
Prostate ; 79(14): 1647-1657, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31433071

RESUMO

BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer morbidity and mortality in men worldwide; however, PCa incidence and mortality rates vary widely across geographic regions and ethnic groups. The current study was designed to elucidate the pivotal factors involved in PCa occurrence and development. METHODS: We performed RNA sequencing on the prostate tumor and adjacent normal tissues from Chinese PCa patients. Genes identified via genome-wide expression profile analysis were validated by quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. Hypermethylation of CpG islands was assessed by nested methylation-specific PCR. Whole genome microarray analysis was performed using an Affymetrix GeneChip. RESULTS: We identified nine possible abnormally expressed genes (P < .05) and then revealed TWIST2 as having strikingly lower expression in tumors than in control tissues (P < .01). Low messenger RNA expression levels of TWIST2 were associated with hypermethylation of CpG islands in its promoter region. In accordance with these findings, PCa tumor tissues showed markedly decreased TWIST2 protein expression compared to that in both normal and prostatic intraepithelial neoplasia tissues by immunohistochemical staining. Ectopic expression of TWIST2 in LNCap cells not only inhibited cell proliferation and colony formation in vitro and tumor growth in vivo but also induced transcriptional repression of a cell proliferation-related gene cohort, including androgen receptor signaling mediators, cyclins, homeobox genes, forkhead box genes, and SOX2. CONCLUSIONS: Our results suggest that TWIST2 could function as a tumor suppressor involved in the pathogenesis of PCa by influencing the expression of target genes and that hypermethylation of the TWIST2 promoter in prostate tumors may be an underlying mechanism for TWIST2 transcriptional silencing.


Assuntos
Neoplasias da Próstata/genética , Proteínas Supressoras de Tumor , Proteína 2 Relacionada a Twist/genética , China , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise em Microsséries , Regiões Promotoras Genéticas , Neoplasia Prostática Intraepitelial/química , Neoplasias da Próstata/química , RNA Mensageiro/análise , Análise de Sequência de RNA , Células Tumorais Cultivadas , Proteína 2 Relacionada a Twist/análise , Proteína 2 Relacionada a Twist/fisiologia
6.
Chem Commun (Camb) ; 55(64): 9535-9538, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31334508

RESUMO

Endoperoxide-containing antimalarials, such as artemisinin and the synthetic trioxolane OZ439, are prodrugs activated by heme to generate primary and secondary carbon-centered radicals. We employed activity-based protein profiling (ABPP) to show that the secondary-carbon-centered radical of 1,2,4-trioxolanes is primarily responsible for protein labeling in malaria parasites.


Assuntos
Carbono/metabolismo , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Animais
7.
Int J Environ Res Public Health ; 13(2): 162, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26828504

RESUMO

Prostate cancer (PCa) is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI), smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR) and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or ≥3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs) = 1.79-4.41). GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI ≥ 28 had ORs of 7.66 (p = 0.032) and 5.33 (p = 0.046), respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007) and 3.11 (p = 0.024), respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041). These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Povo Asiático/genética , Saúde do Homem , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Adulto , Idoso , Alelos , Índice de Massa Corporal , Estudos de Casos e Controles , China/epidemiologia , Interação Gene-Ambiente , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Neoplasias da Próstata/epidemiologia , Risco , Fumar/efeitos adversos , Inquéritos e Questionários
8.
Genet Test Mol Biomarkers ; 20(2): 81-5, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26741812

RESUMO

OBJECTIVE: Shared genetic variants in ADIPOR1 have been identified as closely related to coronary artery disease (CAD), type 2 diabetes (T2D), and T2D with CAD susceptibility, suggesting that these variants are strong candidates for the common soil hypothesis. Therefore, it is essential to analyze the relationship between ADIPOR1 variants and the susceptibility to CAD, T2D, and T2D with CAD in other populations. MATERIALS AND METHODS: A case-control study was conducted which included three case cohorts [CAD (n = 316), T2D (n = 295), T2D with CAD (n = 302)], and a control cohort (n = 268) from a population in northeast China. Six ADIPOR1 single-nucleotide polymorphisms were genotyped by high-resolution melting and polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We confirmed that the shared variant, rs3737884*G, in ADIPOR1 is associated with CAD, T2D, and T2D with CAD (p-value range: 6.54E-6-1.82E-5, odds ratio [OR] range: 1.770-1.844) and that rs16850797*C is associated with T2D and T2D with CAD (p-value range: 0.001-0.001, OR range: 1.529-1.571). We also found that a novel shared variant, rs7514221*C, is associated with an increased susceptibility to CAD, T2D, and T2D with CAD (p-value range: 0.002-0.004, OR range: 1.194-2.382) in this population. CONCLUSIONS: ADPOR1 variants, rs3737884*G and rs7514221*C, may be shared risk factors associated with CAD, T2D, and T2D with CAD in a population of northeast China.


Assuntos
Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Receptores de Adiponectina/genética , Povo Asiático , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
9.
Clin Lab ; 61(10): 1491-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26642711

RESUMO

BACKGROUND: The tumor suppressor forkhead box P4 (FOXP4) plays important roles in oncogenesis, and the FOXP4 variant rs1983891 is associated with prostate cancer (PCa) in several studies. However, association studies conducted in Northern and Southern Chinese have provided conflicting results. Therefore, here we performed fine mapping of FOXP4 to identify the association with PCa and the potential application in Chinese men. METHODS: We examined 11 variants spaced approximately 55 kb apart spanning FOXP4 using high-resolution melting-curve analysis and sequencing methods in 286 PCa patients and 630 controls, and the association between these variants and PCa risk was evaluated. Additionally, we evaluated the cumulative effect of rs4714476 and 2 variants in 8q24 (rs16901966, rs10090154) confirmed in our previous study. RESULTS: Of 11 SNPs, only rs4714476-C at the 5' near gene of FOXP4 was associated with increased age-adjusted PCa risk (p = 0.012, OR = 1.32, 95% CI = 1.06 - 1.63) and aggressive PCa (p = 0.026). The CG haplotype covering rs4714476-C demonstrated significant differences between PCa cases and controls (p = 0.009). The cumulative effect analysis showed men who carried any combination of 1, 2, or 3 risk genotypes had a gradually increased PCa risk (age-adjusted OR is from 1.244 to 3.312). CONCLUSIONS: These data suggest that rs4714476 at the 5' near gene of FOXP4 potentially contributes to the susceptibility of PCa in Chinese men. The cumulative effect of rs4714476 at FOXP4 and 8q24 could increase PCa risk.


Assuntos
Fatores de Transcrição Forkhead/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Estudos de Casos e Controles , China , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/etnologia , Fatores de Risco , Análise de Sequência de DNA
10.
J Clin Endocrinol Metab ; 100(11): 4198-207, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26308292

RESUMO

CONTEXT: An excess circulating uric acid level, even within the normal range, is always comorbid with metabolic syndrome (MS), several of its components, and nonalcoholic fatty liver disease (NAFLD), which was regarded as hepatic manifestation of MS; however, these associations remain controversial. OBJECTIVE: This study aimed to quantitatively assess the relationship between the serum uric acid (SUA) levels and the MS/NAFLD risk. DESIGN: We searched for related prospective cohort studies including SUA as an exposure and MS/NAFLD as a result in MEDLINE (PubMed) and EMBASE databases up to January 31, 2015 and July 28, 2015, respectively. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were extracted. A random-effects model was used to evaluate dose-response relationships. MAIN OUTCOMES: On the basis of 11 studies (54 970 participants and 8719 MS cases), a combined RR of 1.72 (95% CI, 1.45-2.03; P < .0001) was observed for the highest SUA level category compared with the lowest SUA level category. Furthermore, based on nine studies (51 249 participants and 8265 MS cases), dose-response analysis suggested that each 1 mg/dL SUA increment was roughly linearly associated with the MS risk (RR, 1.30; 95% CI, 1.22-1.38; P < .0001). Beyond that, SUA level increased NAFLD risk (RR, 1.46; 95% CI, 1.31-1.63). Each 1 mg/dL SUA level increment led to 21% increase in the NAFLD risk. CONCLUSIONS: This meta-analysis suggests that higher SUA levels led to an increased risk of MS regardless of the study characteristics, and were consistent with a linear dose-response relationship. In addition, SUA was also a causal factor for the NAFLD risk.


Assuntos
Síndrome Metabólica/urina , Ácido Úrico/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/urina , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Adulto Jovem
11.
Yi Chuan ; 37(1): 17-24, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25608809

RESUMO

Twist2, one of the basic helix-loop-helix protein (bHLH) family members, is responsible for the transcriptional regulation in mesenchymal cell lineages during its development. Twist2 functions as a molecular switch to activate or repress target genes by direct or indirect mechanisms. Twist2 can directly bind with conserved E-box on DNA sequence, to recruit co-activators or repressors, and interfere with the activation or inhibition function through protein-protein interactions with E-protein modulators. Nonsense mutations of Twist2 cause Setleis syndrome. Early research on Twist2 focused on osteogenesis, and then expression differences were found in a wide variety of tumors. Further studies showed that Twist2 plays an important role in cancer epithelial-mesenchymal transition (EMT). Regulation function of Twist2 is controlled by temporal and spatial expression, phosphorylation, dimerization and cell positioning adjustment. The involvement of Twist2 in a broad spectrum of regulatory pathways highlights the importance of understanding its role in normal development, homeostasis and disease. In this review, we summarize the role of Twist2 in osteogenesis differentiation, tumor formation and EMT, and its molecular mechanism. It is helpful to have a thorough understanding of the biological functions of Twist2, and facilitate the transformation and application in diagnosis, development and therapy.


Assuntos
Neoplasias/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Animais , Diferenciação Celular , Transição Epitelial-Mesenquimal , Humanos , Neoplasias/genética , Neoplasias/fisiopatologia , Proteína 1 Relacionada a Twist/genética
12.
Asian Pac J Cancer Prev ; 15(19): 8311-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25339022

RESUMO

BACKGROUND: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations. MATERIALS AND METHODS: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically- confirmed PCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphism was genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed the associations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed using genotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studies in American and European populations, to determine the association between PCa and risk genotype. RESULTS: The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140, P=7.3?10-5), suggesting that the 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjects were in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91, Padj=1.1?10-4). Presence of the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis ≥65 years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared with the non-risk genotype (P=4.6?10-5-3.0?10-2). Meta-analysis confirmed the association between 8q24 rs4242382-A polymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88, P=1.0?10-5) across Asian, Caucasian and African American populations. CONCLUSIONS: The replicated data suggest that the 8q24 rs4242382-A variation might be associated with increased PCa susceptibility in Asian, Caucasian and African American populations. These results imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations.


Assuntos
Cromossomos Humanos Par 8/genética , Predisposição Genética para Doença , Polimorfismo Genético/genética , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Humanos , Masculino , Prognóstico , Fatores de Risco
13.
Zhongguo Yi Liao Qi Xie Za Zhi ; 38(3): 193-5, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-25241514

RESUMO

The existing analog reordering and folding technology has the following problems: it cause the attenuation of the ultrasonic signal, and it is difficult to achieve beam steering in color Doppler ultrasonic diagnostic instrument. This article proposes a design method to achieve digital reordering of dynamic focusing data. The digital reordering is composed of two parts, bit reordering which is implemented with multiplier and byte reordering using switch selection. The results show that it can meet the design requirements using fewer resources.


Assuntos
Processamento de Sinais Assistido por Computador , Ultrassom , Aumento da Imagem
14.
Eur J Pharmacol ; 734: 9-14, 2014 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-24726849

RESUMO

Endothelial tight junction is a crucial intracellular junctional structure that controls paracellular permeability across vascular endothelium. Oxidative stress-mediated elevation in endothelial permeability is associated with pathogenesis of several cardiovascular diseases. In the present research, the regulation of farrerol on occludin, a transmembrane proteins associated with endothelial tight junction, was investigated in hydrogen peroxide-induced human endothelium-derived EA.hy926 cells. Western blot analysis demonstrated that H2O2 exposure caused a significant decrease in occludin expression, but had little effect on ZO-1 expression, and the decrease of occludin expression was significantly attenuated by farrerol in a dose-dependent manner. Meanwhile, immunofluorescent staining assay also demonstrated that the loss of occludin expression induced by H2O2 exposure was restored by farrerol pretreatment. Further investigations showed that farrerol prevented H2O2-induced activation of extracellular signal-regulated kinase (ERK) 1/2 in a dose-dependent manner. The use of U0126, a specific inhibitor of MEK1/2, proved that H2O2-induced decrease of occludin in EA.hy926 cells was likely associated with activation of ERK1/2, which indicated that the regulation of farrerol on occludin expression in H2O2-induced EA.hy926 cells was likely related to the modulation of ERK1/2 activation. In conclusion, the present study demonstrates for the first time that farrerol has potential effects on oxidative stress-induced endothelial tight junction disruption and suggests that farrerol is a potential candidate for the intervention of endothelial permeability-associated cardiovascular diseases.


Assuntos
Cromonas/farmacologia , Peróxido de Hidrogênio/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Ocludina/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Permeabilidade/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo
15.
Oncol Res Treat ; 37(3): 106-10, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24685913

RESUMO

BACKGROUND: The single nucleotide polymorphism (SNP) rs1465618 in THADA at 2p21 has been identified as being associated with prostate cancer (PCa) risk in Europeans; however, it is not clear whether the SNP is related to PCa risk in multiple populations. We investigated the association of rs1465618 in THADA with PCa in a Chinese population and carried out a meta-analysis in multiple populations, testing the relevance of this SNP for PCa risk. PATIENTS AND METHODS: We genotyped the SNP using high resolution melting (HRM) analysis and assessed its association with PCa risk in a case-control study of 289 PCa patients and 288 controls in a Chinese population. A meta-analysis was carried out with 36,313 PCa patients and 36,485 controls to evaluate the association of rs1465618 with PCa risk in multiple populations. RESULTS: rs1465618 in THADA was significantly associated with PCa risk (p = 0.026; odds ratio (OR) 1.327, 95% confidence interval (CI) 1.035-1.700). Furthermore, the rs1465618 variant genotype was associated with PCa aggressiveness (p = 0.044; OR = 2.053, 95% CI = 1.015-6.602) in the Chinese population. The meta-analysis showed that rs1465618 was significantly associated with PCa risk in multiple populations (p = 1.0×10(-8); OR = 1.127, 95% CI = 1.085-1.171). CONCLUSION: Our results showed that rs1465618 in THADA may be a shared susceptibility variant for PCa in multiple populations. THADA gene polymorphisms may impact PCa susceptibility and progression.


Assuntos
Biomarcadores Tumorais/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Idoso , China/epidemiologia , Marcadores Genéticos/genética , Humanos , Masculino , Prevalência , Neoplasias da Próstata/diagnóstico , Medição de Risco
16.
Asian Pac J Cancer Prev ; 14(11): 6733-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24377597

RESUMO

Multiple genetic studies have confirmed association of 8q24 variants with susceptibility to prostate cancer (PCa). As PCa risk SNPs may also influence disease outcome, we studied here eight 8q24 risk alleles, and evaluated their role in PCa clinical covariates in northern Chinese men. Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically-confirmed PCa (n=289) and from age-matched normal controls (n=288). Eight 8q24 SNPs were genotyped by polymerase chain reaction- high-resolution melting analysis in 577 subjects. We examined the prevalence distribution of 8q24 risk alleles and analyzed the associations between the risk allele and PCa and clinical covariates to infer their impact on aggressive PCa. Three of the eight SNPs were associated with PCa risk in northern Chinese men, including rs16901966 (OR 1.31, 95% CI 1.01-1.70, p=0.042), rs1447295 (OR 1.47, 95% CI 1.09-1.98, p=0.011) and rs10090154 (OR 1.55, 95% CI 1.14-2.12, p=0.005). Haplotype analysis based association with the risk alleles revealed significant differences between cases and controls (OR 1.43, 95%CI 0.99-2.06, p=0.049). The risk alleles rs16901966, rs1447295 and rs10090154 were associated with age at diagnosis and tumor stage as compared with controls, while rs16901966 was associated with aggressive PCa (OR 1.43, 95% CI 1.01-2.03, p=0.042). The evidence for 8q24 SNPs with PCa risk in northern Chinese men showed rs16901966, rs1447295 and rs10090154 at 8q24 (region 1, region 2) to be strongly associated with PCa and clinical covariates. The three SNPs at 8q24 could be PCa susceptible genetic markers in northern Chinese men.


Assuntos
Cromossomos Humanos Par 8/genética , Polimorfismo de Nucleotídeo Único/genética , Próstata/metabolismo , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Seguimentos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia
17.
Asian Pac J Cancer Prev ; 14(5): 3075-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23803082

RESUMO

BACKGROUND: KLK3 gene products, like human prostate-specific antigen (PSA), are important biomarkers in the clinical diagnosis of prostate cancer (PCa). G protein-coupled receptor RFX6, C2orf43 and FOXP4 signaling plays important roles in the development of PCa. However, associations of these genes with PCa in northern Chinese men remain to be detailed. This study aimed to investigate their impact on occurrence and level of malignancy. METHODS: All subjects were from Beijing and Tianjin, including 266 cases with prostate cancer and 288 normal individuals as controls. We evaluated associations between clinical covariates (age at diagnosis, prostate specific antigen, Gleason score, tumor stage and aggressive) and 6 candidate PCa risk loci, genotyped by PCR- high resolution melting curve and sequencing methods. RESULTS: Case-control analysis of allelic frequency of PCa associated with PCa showed that one of the 6 candidate risk loci, rs339331 in the RFX6 gene, was associated with reduced risk of prostate cancer (odds ratio (OR) = 0.73, 95% confidence interval (CI) =0.57-0.94, P = 0.013) in northern Chinese men. In addition, subjects with CX (CC+TC) genotypes had a decreased risk for prostrate cancer compared to those carrying the TT homozygote (OR =0.64, 95% CI = 0.45- 0.90, P = 0.008). The TT genotype of 13q22 (rs9600079, T) was associated with tumor stage (P=0.044, OR=2.34, 95% CI=0.94-5.87). Other SNPs were not significantly associated with clinical covariates in prostate cancer (P > 0.05). CONCLUSIONS. rs339331 in the RFX6 gene may be associated with prostate cancer as a susceptibility locus in northern Chinese men.


Assuntos
Povo Asiático/genética , Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Próstata/metabolismo , Neoplasias da Próstata/genética , Fatores de Transcrição/genética , Idoso , Estudos de Casos e Controles , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/patologia , Fatores de Transcrição de Fator Regulador X , Fatores de Risco
18.
Med Chem ; 9(2): 303-11, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22946534

RESUMO

A series of new halophenols were synthesized, and their structures were established on the basis of 1H, 13C NMR and mass spectral data. All of the prepared compounds were screened for their in vitro protein tyrosine kinase (PTK) and vascular smooth muscle cell (VSMC) proliferation inhibitory activity. Twelve halophenols showed significant PTK inhibitory activity, most of them exhibited stronger activities than that of genistein, a positive reference compound. Several halophenols also displayed moderate VSMC proliferation inhibitory activity, compound 8c showed higher activity than that of tetrandrine, a positive reference compound. The preliminary structure-activity relationships of these compounds were investigated and discussed. The results provided a foundation for the action mechanism study and further structure optimization of the halophenols.


Assuntos
Halogenação , Fenóis/síntese química , Fenóis/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Furanos/química , Concentração Inibidora 50 , Masculino , Camundongos , Músculo Liso Vascular/citologia , Fenóis/química , Inibidores de Proteínas Quinases/química , Proteínas Tirosina Quinases/antagonistas & inibidores , Ratos , Relação Estrutura-Atividade
19.
Asian Pac J Cancer Prev ; 13(12): 6273-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23464444

RESUMO

BACKGROUND/AIM: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. METHODS: Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. RESULTS: Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). CONCLUSION: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.


Assuntos
Povo Asiático/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Neoplasias da Próstata/genética , Idoso , Alelos , Estudos de Casos e Controles , Frequência do Gene/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Risco , População Branca/genética
20.
Langmuir ; 27(7): 3945-51, 2011 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-21395274

RESUMO

We studied hydrogen-bonding assemblies in a series of dumbbell-shaped hydrazine derivatives, namely oxalyl N',N'-bis(3,4-dialkoxybenzoyl)-hydrazide (BFH-n, n = 4, 6, 8, 10) and oxalyl N',N'-dibenzoyl-hydrazide (FH-0). It has been demonstrated that NH-1 protons of BFH-n precipitated from tetrahydrofuran (THF) or dimethylformamide (DMF) were involved in intramolecular H-bonding to form 6-membered rings. Meanwhile, NH-2 protons of BFH-n precipitated from THF formed intermolecular hydrogen bonds with C═O groups of neighboring molecules, while NH-2 protons of BFH-n precipitated from DMF formed intermolecular hydrogen bonds with C═O group of neighboring DMF molecules. C═O, -CH(3), and -CH groups of DMF molecules participated in multiple intermolecular hydrogen bonds with the -N-H and -C═O groups of FH-0 molecules in single-crystals formed in DMF, leading to a double helix morphology with a pitch of 24.2 Šalong the c direction. Both left- and right-handed helical micrometer-length ribbons with nonuniform helical pitches were observed in an achiral BFH-10 xerogel precipitated from DMF.


Assuntos
Hidrazinas/química , Solventes/química , Dimetilformamida/química , Furanos/química , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Modelos Moleculares , Conformação Molecular
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