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1.
Org Lett ; 26(11): 2212-2217, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38452132

RESUMO

In this report, we present a photopromoted, metal-free transannulation of phenyl azides for the synthesis of DNA-encoded seven-membered rings. The transformation is efficiently achieved through a skeletal editing strategy targeting the benzene motif coupled with a Reversible Adsorption to Solid Support (RASS) strategy. A variety of valuable DNA-encoded seven-membered ring compounds, including DNA-encoded 3H-azepines, azepinones, and unnatural amino acids, are now accessible. Crucially, this DNA-compatible protocol can also be applied for the introduction of complex molecules, as exemplified by Lorcaserin and Betahistine. The selective conversion of readily available phenyl rings into high-value seven-membered rings offers a promising avenue for the construction of diversified and drug-like DNA-encoded library.


Assuntos
Azidas , Benzeno , Ciclização , Aminas , DNA
2.
Dis Markers ; 35(5): 489-96, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24223461

RESUMO

In this study, the two-step PV method of immunohistochemistry was used to determine livin protein expression in HCC tissues, pericarcinoma tissues, hepatitis/hepatic cirrhosis tissues, and normal hepatic tissues, and livin protein expression was detected in the blood plasma of patients with HCC before and after surgery, subjects with hepatic cirrhosis and hepatitis, and healthy blood donors using ELISA. Livin protein expression was significantly higher in HCC tissues than that in normal hepatic tissues and hepatitis/hepatic cirrhosis tissues, with no significant difference between HCC tissues and pericarcinoma tissues. The HCC patients with positive livin protein expression had a significantly higher survival rate than those with negative livin protein expression. Livin protein expression was significantly higher in the blood plasma of patients with HCC before and after surgery and in patients with hepatic cirrhosis and hepatitis than that in healthy blood donors, whereas livin protein expression in the blood plasma of patients with HCC was not significantly different from that of patients with hepatic cirrhosis and hepatitis. Livin protein expression in HCC tissues did not correlate with that in the blood plasma of the same HCC patients. Livin protein expression may be a potential, effective indicator for assessing prognosis in patients with HCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Proteínas Inibidoras de Apoptose/genética , Neoplasias Hepáticas/diagnóstico , Fígado/patologia , Proteínas de Neoplasias/genética , Proteínas Adaptadoras de Transdução de Sinal/sangue , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Feminino , Fibrose/sangue , Fibrose/diagnóstico , Fibrose/metabolismo , Hepatite/sangue , Hepatite/diagnóstico , Hepatite/metabolismo , Humanos , Proteínas Inibidoras de Apoptose/sangue , Proteínas Inibidoras de Apoptose/metabolismo , Fígado/metabolismo , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/metabolismo
3.
Zhonghua Liu Xing Bing Xue Za Zhi ; 32(11): 1143-7, 2011 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-22336553

RESUMO

OBJECTIVE: To investigate the correlation between IL-28B rs8099917 polymorphism and the outcome of HBV infection. METHODS: Genotype of rs8099917 (T > G) in IL-28B locus was determined by TaqMan SNP genotyping from 486 individuals which including 199 chronic HBV carriers (including 100 HBV-induced liver cirrhosis and 99 HBV-related HCC). 143 people with self-limited infection and 144 healthy people served as controls. Multivariate analysis was used to assess the effect of IL-28B rs8099917 SNP among all the studied groups. RESULTS: Distribution of genotype and allele of the rs8099917 locus were in accordance with Hardy-Weinberg equilibrium in different groups or with the total population. The frequencies of the rs8099917 TT, GT, GG genotypes were 89.3%, 10.5% and 0.2%, and the frequency of allele T and G accounted for 94.5% and 5.5%, respectively. In respect of genotype or allele frequency, there was no significant differences found among the groups (P > 0.05). When comparing with the TT genotype, data from the multinomial logistic analysis showed that the ORs and (95%CI) of TG/GG genotypes were 1.589 (0.735 - 3.437), 1.351 (0.550 - 3.316) and 1.704 (0.717 - 4.052), respectively. The genotype frequencies in different groups with different clinical features showed that TG/GG genotypes significantly increased the risk of r-GTII(+) for individuals with HBV-related HCC (χ(2) = 17.534, P = 0.001), with OR as 14.821 (3.227 - 68.064). It was particularly so for males (χ(2) = 14.924, P = 0.014), with OR (95%CI) as 45.000 (2.772 - 730.571). CONCLUSION: IL-28B rs8099917 SNP had no correlation with the outcome of HBV infection.


Assuntos
Hepatite B/genética , Interleucinas/genética , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Interferons , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico
4.
Zhonghua Zhong Liu Za Zhi ; 31(7): 485-9, 2009 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-19950693

RESUMO

OBJECTIVE: To investigate the mechanisms that coagulation factor VIIa promotes proliferation and migration of a colon cancer cell line (SW620 cells) in vitro. METHODS: The expression of interleukin 8 (IL-8), tissue factor (TF), caspase-7 and p-p38 MAPK in SW620 cells treated with factor VIIa or protease activated receptor 2 agonist (PAR2-AP) was measured by ELISA, Western-blotting and QT-PCR. RESULTS: Factor VIIa and PAR2-AP induced IL-8 expression at both mRNA and protein levels, upregulated TF mRNA expression and TF activity, but down-regulated caspase-7 mRNA and p-p38 MAPK levels in SW620 cells. The effects of factor VIIa were not only blocked by anti-TF but also by anti-PAR2 antibodies. CONCLUSION: Factor VIIa binds to TF on cell surface, forming a complex which activates PAR2, then provoking IL-8 and TF expression, and suppresses caspase-7 expression, thus promotes the tumor cell proliferation and migration. p38 MAPK may negatively regulate this process.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Fator VIIa/farmacologia , Caspase 7/biossíntese , Caspase 7/genética , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Humanos , Interleucina-8/biossíntese , Interleucina-8/genética , Oligopeptídeos/farmacologia , RNA Mensageiro/metabolismo , Receptor PAR-2/agonistas , Tromboplastina/biossíntese , Tromboplastina/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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