RESUMO
Gastric cancer is the fourth most common cancer in the world and the second leading cause of death in cancer worldwide. In order to reduce the mortality rate of gastric cancer, the problem that needs to be solved at present is to find new specific markers of early gastric cancer and increase the detection rate of early gastric cancer, thus fundamentally solving the problem of high mortality of gastric cancer. Previous studies in our laboratory found that Peroxiredoxin 4 (PRDX4) has the potential for early gastric cancer markers. In this study, the role of PRDX4 in transformed cells was studied by establishing a malignant transformation model and transforming cell overexpression, the experiment proves that PRDX4 is responsible for growth and proliferation by reducing the content of reactive oxygen species (ROS) in transformed cells. In the microenvironment, it promotes the malignant transformation of cells, that is, PRDX4 promotes the development of gastric cancer via eliminating ROS.
Assuntos
Neoplasias Gástricas , Carcinogênese , Transformação Celular Neoplásica , Humanos , Peroxirredoxinas , Espécies Reativas de Oxigênio , Neoplasias Gástricas/diagnóstico , Microambiente TumoralRESUMO
PURPOSE: To investigate how Sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) promotes high glucose-attenuated corneal epithelial wound healing. METHODS: The effects of high glucose on SIRT1 expression were assessed in primary human corneal epithelial cells (CECs) in treatment of 5 mM d-glucose (normal glucose [NG]) and 25 mM D-glucose (high glucose [HG]) and corneas from Ins2(Akita/+) mice by Western blotting. The osmotic pressure of the NG medium was adjusted to that of the HG medium by adding 20 mM mannitol. Pifithrin-α (PFT-α) was used to inhibit the expression of p53 and an adenovirus was used for overexpression of SIRT1 in vivo and in vitro. How overexpression of SIRT1 promotes HG-attenuated corneal epithelial wound healing via p53 regulation of the IGFBP3 (insulin-like growth factor binding protein-3)/IGF-1 (insulin-like growth factor-1)/AKT pathway was investigated in CECs and Ins2(Akita/+) mice. RESULTS: HG induced the downregulation of SIRT1 and the upregulation of p53 acetylation in primary human CECs and corneas from Ins2(Akita/+) mice. The results of cell migration assay and corneal wound healing from Ins2(Akita/+) mice demonstrated that SIRT1 overexpression strongly promoted wound healing in the presence of HG levels via the downregulation of the IGFBP3 protein. The levels of total p53 expression and acetylated p53 decreased dramatically in the presence of PFT-α, whereas the IGF-1R/AKT pathway was activated in CECs. The results of cell migration assay suggested this posttranslational modification of p53 was involved in the response to cell injury under HG conditions in CECs. CONCLUSIONS: The molecular mechanism by which SIRT1 promotes corneal epithelial wound healing was involved in an enhancement of the IGFBP3/IGF-1/AKT pathway through the deacetylation of p53. This study also suggests that SIRT1 has a protective role in the pathogenesis of diabetic keratopathy.
Assuntos
Epitélio Corneano/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Glucose/farmacologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteínas Quinases/metabolismo , Sirtuína 1/genética , Proteína Supressora de Tumor p53/metabolismo , Cicatrização/efeitos dos fármacos , Animais , Benzotiazóis/farmacologia , Western Blotting , Células Cultivadas , Regulação para Baixo , Epitélio Corneano/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptor IGF Tipo 1/metabolismo , Tolueno/análogos & derivados , Tolueno/farmacologia , Proteína Supressora de Tumor p53/antagonistas & inibidoresRESUMO
The effects of oligosaccharide and creatine (Cr) supplementation on glucose, lactic acid and urea nitrogen levels in blood and activity of serum creatine kinase (CK) were explored. Twenty CUBA male athletes were divided into 4 groups: group A (supplementation of Cr alone), group B (supplementation of oligosaccharide), group C (supplementation of oligosaccharide and Cr) and group D (placebo control group). By using orthogonal L4 table (2(3)), the experiment was performed. There were factors including oligosaccharide (carbohydrate, CHO), Cr and their correlation. Each factor had two levels: supplementation and no-supplementation. The results showed that the supplementation of CHO or Cr alone, combined supplementation of CHO and Cr could significantly reduce the glucose, urea nitrogen levels in blood and serum CK activity after competition in the athletes. Moreover, the effects of combined supplementation of CHO and Cr were more satisfactory. It was concluded that supplementation of CHO and Cr could promote the recovery of physical performance and athletic abilities after athletics in basketball athletes.
