RESUMEN

OBJECTIVE: This study was performed to investigate bone deteriorations of diabetic mice in response to the treatment of ursolic acid derivative (UAD). METHODS: The biomarkers in serum and urine were measured, tibias were taken for the measurement on gene and protein expression and histomorphology analysis, and femurs were taken for the measurement on bone Ca and three-dimensional architecture of trabecular bone. RESULTS: UAD showed a greater increase in bone Ca, BMD and significantly increased FGF-23 and OCN, reduced PTH and CTX in diabetic mice. UAD reversed STZ-induced trabecular deleterious effects and stimulated bone remodeling. The treatment of STZ group with UAD significantly elevated the ratio of OPG/RANKL. Moreover, insulin and IGF-1 showed a negative correlation with both FBG and Hb1Ac in STZ group. We attributed down-regulating the level of Hb1Ac in diabetic mice to that ursolic acid derivative could primely control blood sugar levels. After analyzing of two adipocyte markers, PPARγ and aP2, increased expression in the tibias of diabetic mice, and UAD could improve STZ-induced adipocyte dysfunction. CONCLUSIONS: These results demonstrated that UAD could ameliorate STZ-induced bone deterioration through improving adipocyte dysfunction and enhancing new bone formation and inhibiting absorptive function of osteoclast in the bone of diabetic mice.

Asunto(s)

Densidad Ósea/efectos de los fármacos , Diabetes Mellitus Experimental/fisiopatología , Fémur/efectos de los fármacos , Tibia/efectos de los fármacos , Triterpenos/farmacología , Animales , Calcio/metabolismo , Fémur/metabolismo , Fémur/fisiopatología , Factor-23 de Crecimiento de Fibroblastos , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Osteoprotegerina/sangre , Ligando RANK/sangre , Tibia/metabolismo , Tibia/fisiopatología , Ácido Ursólico

RESUMEN

The dysregulation of apoptosis plays a key role in carcinogenesis. This study was designed to investigate the association of apoptosis-related gene survivin A9194G single-nucleotide polymorphisms (SNPs) with papillary thyroid carcinoma (PTC) susceptibility. A case-control study of 126 patients and 198 controls was performed to investigate the association between Survivin A9194G polymorphisms and PTC susceptibility by polymerase chain reaction (PCR) following DNA sequencing methods. Moreover, the distribution of genotype frequency and the association of genotype with clinicopathologic characteristics were analyzed. We found that the survivin A9194G genotype was at a decreased risk of PTC (P=0.003; odds ratio (OR)=0.56). Furthermore, compared to the PTCs of the AA and AG phenotypes, the GG genotype thyroid cancers were significantly more common in younger patients and in cases of lower pathologic stages. In conclusion, the survivin (A9194G) polymorphism was found to play a protective role in the susceptibility to PTC. Nevertheless, further investigation with a larger sample size is needed to support our results.

Asunto(s)

Pueblo Asiatico/genética , Carcinoma/genética , Predisposición Genética a la Enfermedad/genética , Proteínas Inhibidoras de la Apoptosis/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Tiroides/genética , Adulto , Anciano , Carcinoma/patología , Carcinoma Papilar , Estudios de Casos y Controles , Exones , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Factores de Riesgo , Survivin , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología

RESUMEN

The aim of this study is to investigate the associations between E-cadherin gene (CDH1) polymorphisms and papillary thyroid carcinoma (PTC) risk predisposition. We undertook a case-control study to analyze three CDH1 polymorphisms (+54T>C, -160C>A, and -347G→GA) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 98 patients with PTC and 176 control participants, and performed CDH1 genotyping using DNA sequencing. The obtained results indicated that overall, no statistically significant association was observed in +54T>C. Nevertheless, -347G→GA genotype was at increased risk of PTC (P = 0.001; odds ratio (OR) = 2.12, CI 95%:1.24-3.34). Furthermore, -347GA/GA genotype thyroid cancers were more significantly common in patients with tumor size of ≥20 mm than G or G/GA genotypes PTC and in cases of advanced T stage. However, -160C>A genotype demonstrated a protective effect in PTCs (P = 0.006; OR = 0.59, CI 95%: 0.42-0.87). These findings led us to conclude that polymorphism in -347G→GA was observed to be associated with susceptibility of PTC. However, -160C>A polymorphism indicated to play a protective role in susceptibility to PTC. Nevertheless, further investigation with a larger sample size is needed to support our results.

Asunto(s)

Cadherinas/genética , Carcinoma/genética , Polimorfismo Genético , Neoplasias de la Tiroides/genética , Adulto , Anciano , Antígenos CD , Pueblo Asiatico/genética , Células Sanguíneas/metabolismo , Cadherinas/sangre , Carcinoma/sangre , Carcinoma/patología , Carcinoma Papilar , Estudios de Casos y Controles , China , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mutagénesis Insercional , Estadificación de Neoplasias , Polimorfismo de Nucleótido Simple , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/patología , Carga Tumoral

RESUMEN

Dysregulation of apoptosis plays a key role in carcinogenesis. This study was designed to investigate the association of apoptosis-related gene Caspase 8, Caspase 9 and Bcl-2 polymorphisms with papillary thyroid carcinoma (PTC) susceptibility. We undertook a case-control study of 118 patients and 213 controls to investigate the association between Caspase 8 (-652 6 N ins/del), Caspase 9 (-1263 A>G) and Bcl-2 (-938 C>A) polymorphisms and PTC susceptibility by polymerase chain reaction restriction-fragment length polymorphism and DNA sequencing methods. We further analyzed the distribution of genotype frequency, as well as the association of genotype with clinicopathological characteristics. Overall, no statistically significant association was observed in Caspase 8 (-652 6 N ins/del). Nevertheless, Caspase 9 -1263 GG genotype was at increased risk of PTC (P=0.045; odds ratio (OR)=1.12). Furthermore, GG genotype thyroid cancers were significantly more common in older patients than AA or AG genotypes PTC and in cases of advanced pathological stages. However, Bcl-2 -938 AA genotype demonstrated a protective effect in PTCs (P=0.004; OR=0.35). Polymorphism in Caspase 9 (-1263 A>G) was observed to be associated with susceptibility of PTC. However, Bcl-2 (-938 C>A) polymorphism indicated to play a protective role in susceptibility to PTC. Nevertheless, further investigation with a larger sample size is needed to support our results.

Asunto(s)

Pueblo Asiatico/genética , Carcinoma/genética , Caspasa 8/genética , Caspasa 9/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Proteínas Proto-Oncogénicas c-bcl-2/genética , Neoplasias de la Tiroides/genética , Adulto , Anciano , Carcinoma/etiología , Carcinoma Papilar , China/etnología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/etiología