[Expression of circadian gene NPAS2 in colorectal cancer and its prognostic significance].

OBJECTIVE: To study the expression of NPAS2 in colorectal cancer (CRC) and analyze its relationship with the clinicopathological parameters and prognosis of the patients. METHODS: Real-time q-PCR was used to detect the expression of NPAS2 mRNA in 40 fresh CRC tissues and paired adjacent tissues; immunohistochemistry was used to detect the expression of NPAS2 protein in 120 paraffin-embedded tumor and adjacent tissues. The relationship between NPAS2 expression level and the 5-year survival rate of 78 CRC patients with follow-up data were analyzed with Kaplan-Meier survival analysis. RESULTS: Compared with the adjacent tissues, fresh CRC tissue expressed significantly lower NPAS2 mRNA levels (P<0.01). Among the paraffin-embedded CRC tissues, 19.2% were positive for NPAS2 expression, as compared to a much higher rate of 62.5% in the adjacent tissues (P<0.05). The expression of NPAS2 was correlated with the tumor size, lymph node metastasis and TNM stages (P<0.05) but not with the patients' gender, age, distant tumor metastasis, differentiation, or invasion. Patients with high NPAS2 expression levels had a significantly higher 5-year survival rate than those with low NPAS2 expressions (P=0.0001). CONCLUSION: NPAS2 is down-regulated in CRC and closely correlated with the malignant biological behavior of the tumor and 5-year survival of the patients, suggesting its value in predicting the prognosis of the CRC patients.

Betaine prevented fructose-induced NAFLD by regulating LXRα/PPARα pathway and alleviating ER stress in rats.

Betaine has been proven effective in treating nonalcoholic fatty liver disease (NAFLD) in animal models, however, its molecular mechanisms remain elusive. The aims of this study were to explore the mechanisms mediating the anti-inflammatory and anti-lipogenic actions of betaine in fructose-fed rats. In this study, betaine improved insulin resistance, reduced body weight gain and serum lipid levels, and prevented hepatic lipid accumulation in fructose-fed rats. It up-regulated hepatic expression of liver X receptor-alpha (LXRα) and peroxisome proliferator-activated receptor-alpha (PPARα), with the attenuation of the changes of their target genes, including hepatic carnitine palmitoyl transferase (CPT) 1α, glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1, apolipoprotein B, sterol regulatory element-binding protein 1c and adipocyte differentiation-related protein, involved in fatty acid oxidation and lipid storage in these model rats. Furthermore, betaine alleviated ER stress and inhibited acetyl-CoA carboxylase α, CPT II, stearoyl-CoA desaturase 1 and fatty acid synthase expression involved in fatty acid synthesis in the liver of fructose-fed rats. Betaine suppressed hepatic gluconeogenesis in fructose-fed rats by moderating protein kinase B -forkhead box protein O1 pathway, as well as p38 mitogen-activated protein kinase and mammalian target of rapamycin activity. Moreover, betaine inhibited hepatic nuclear factor kappa B /nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome activation-mediated inflammation in this animal model. These results demonstrated that betaine ameliorated hepatic lipid accumulation, gluconeogenesis, and inflammation through restoring LXRα and PPARα expression and alleviating ER stress in fructose-fed rats. This study provides the potential mechanisms of betaine involved in the treatment of NAFLD.

[Effect of combination of Ginkgo leaf extract and deferoxamine in preventing and treating ototoxicity of cisplatin].

OBJECTIVE: To observe the effect of combined use of jinnaduo (an injection made by extract of Ginkgo leaf, EGb) and Deferoxamine (DFO, a chelating agent) in antagonizing the ototoxicity of cisplatin (CDDP). METHODS: Guinea pigs were randomly divided into the CDDP group, the EGb group, the DFO group, the combined treated group (EGb + DFO) and the control group. Changes of auditory brain-stem response (ABR), serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, as well as light and scanning electronic microscopic (SEM) figures were observed before and after treatment. RESULTS: The threshold of ABR was significantly higher in the CDDP group than that in the other groups (P<0.01), but was insignificantly different among the latter groups (P>0.05). Serum SOD activity was lower and MDA content was higher in the CDDP group than those in the control group (P<0.01), but in comparison of the two parameters between control and other groups, the difference was insignificant (P>0.05). SEM examination on cochlea showed that the damage of hair cells was milder in the DFO group and the combined treated group than that in the CDDP group, which was slightly milder in the EGb group than that in the CDDP group. CONCLUSION: Combined use of EGb and DFO could effectively reduce the ototoxicity of CDDP, its effect is better than using EGb singly, and similar to that of using DFO alone. The combination could also prevent the side-effect of CDDP in bone marrow inhibition. The Fe ion participated free radical response could be one of the mechanisms of CDDP in damaging hearing.