Protective effect of tauroursodeoxycholic acid on the autophagy of nerve cells in rats with acute spinal cord injury.

OBJECTIVE: To investigate the impact and protective effect of tauroursodeoxycholic acid (TUDCA) on the autophagy of nerve cells in rats with acute spinal cord injury. MATERIALS AND METHODS: Seventy-two 6-8-week-old male Sprague-Dawley (SD) rats were selected and were randomly divided into a sham operation group, a saline control group and a TUDCA treatment group (high and low dose groups). The experimental animals were sacrificed at 24 hours, 5 days and 10 days after spinal cord injury. The Basso, Beattie, Bresnahan locomotor scale was used to assess the hind limb locomotor function after the rats were injured but before sudden death. Electron microscopy, hematoxylin and eosin (HE) staining, TUNEL assays and immunohistochemistry techniques were used to observe the autophagy of the cells. Western blotting was used to analyze the expression of the autophagy-related factor Beclin-1 and the apoptosis-related factor caspase-3, and reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression levels of the above proteins. RESULTS: The locomotor scores of the rats in the saline group were significantly reduced, their Beclin-1 expression levels in neurons were decreased, and caspase-3 expression was increased. The hind limb locomotor scores of rats in the TUDCA groups were decreased, with no difference between the high- and low-dose groups. Beclin-1 expression in their neurons was increased, and caspase-3 expression was decreased; there was a significant difference when compared with the control group, while there was no significant difference between the high- and low-dose groups. CONCLUSIONS: TUDCA significantly activates the neuronal autophagic expression in rats with acute spinal cord injury to inhibit the apoptosis of nerve cells; therefore, it has a protective effect on neurons.

A functional single-nucleotide polymorphism in the ERCC1 gene alters the efficacy of narrowband ultraviolet B therapy in patients with active vitiligo in a Chinese population.

BACKGROUND: T lymphocytes have been shown to cause the destruction of melanocytes in vitiligo pathogenesis. Narrowband ultraviolet B (NB-UVB), as an effective therapeutic strategy in vitiligo, can lead to the formation of DNA photoproducts such as cyclobutane pyrimidine dimers (CPDs) in perilesional lymphocytes and thus induce skin immunosuppression. The repair of DNA photoproducts is performed mainly through the nucleotide excision repair (NER) pathway. We hypothesized that single-nucleotide polymorphisms (SNPs) in NER genes might influence the repair capacity of CPDs and thus contribute to variations in phototherapy efficiency. OBJECTIVES: To detect genetic polymorphisms in NER genes and their relationship with the efficacy of NB-UVB therapy in patients with active vitiligo. METHODS: We investigated the association of NER SNPs (XPA A23G, XPC Ci11A, XPC C2919A and ERCC1 C118T) with phototherapy efficacy in 86 patients with vitiligo who received NB-UVB treatment. Furthermore, we examined the impact of ERCC1 C118T on the apoptosis of T lymphocytes and CPD accumulation after NB-UVB irradiation. RESULTS: We found that patients with vitiligo with the ERCC1 codon 118 CC genotype showed better efficacy after NB-UVB irradiation than those with the ERCC1 118 TT and CT genotypes, whereas no such association was documented among the genotypes of XPA A23G, XPC Ci11A or XPC C2919A. Additionally, the apoptosis rates and CPD levels of lymphocytes after NB-UVB irradiation in patients with the ERCC1 118 CC genotype were significantly higher than those in patients with the ERCC1 118 TT and CT genotypes. CONCLUSIONS: The ERCC1 118 CC genotype confers better efficacy of NB-UVB therapy in patients with active vitiligo.

miR-196a-2 rs11614913 polymorphism is associated with vitiligo by affecting heterodimeric molecular complexes of Tyr and Tyrp1.

Tyrosinase and tyrosinase-related protein 1 (Tyr-Tyrp1) complex plays a critical role in the synthesis of melanin intermediates, which involves the production of reactive oxygen species (ROS) and contributes to the development of vitiligo. Based on our previous observation that rs11614913 single nucleotide polymorphism (SNP) in miR-196a-2 could affect the risk of vitiligo by influencing Tyrp1, we hypothesized that the same SNP could also regulate the level of Tyr in vitiligo. The aim of this study was to evaluate the potential association between rs11614913 SNP in miR-196a-2 and serum Tyr level in vitiligo and the regulatory role of miR-196a-2 in the expression of Tyr in melanocytes. The serum Tyr level was detected in 116 patients with vitiligo and 116 controls by ELISA plate assay. The expression level of Tyrp1 and Tyr in PIG1(normal melanocyte cell lines) cells was analyzed by western blotting. The ROS level and apoptosis rate in PIG1 cells transfected with si-Tyr or control siRNA were tested by flow cytometry. The results show that the individuals with TT+TC genotypes in miR-196a-2 and higher Tyr level in serum had an increased risk of vitiligo compared with those who had the CC genotype and lower Tyr level (P < 0.001). Furthermore, the rs11614913 C allele in miR-196a-2 enhanced its inhibitory regulation on the expression of Tyr, the down-regulation of which in melanocytes successfully reduced the intracellular ROS levels and the apoptosis rate. In conclusion, our findings suggest that miR-196a-2 polymorphisms can regulate the Tyr levels, which influences the susceptibility of vitiligo.