ABSTRACT
Background: Excision repair cross-complementing group 1 (ERCC1) was considered a potential candidate gene for ischemic stroke, and its polymorphisms might be associated with the susceptibility to ischemic stroke. Methods: A total of 513 patients with ischemic stroke and 550 control subjects were recruited. The expression levels of ERCC1 messenger RNA (mRNA) in peripheral blood mononuclear cells and its protein in plasma were detected by quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Rs3212986 polymorphism of ERCC1 was detected by PCR-restriction fragment length polymorphism (RFLP-PCR) and was confirmed by sequencing. The association between the ERCC1 rs3212986 polymorphism or its expression and ischemic stroke was further analyzed. Results: The ERCC1 mRNA level in patients with ischemic stroke was lower than that in the control group (P < 0.05). However, the ERCC1 protein level in patients with ischemic stroke was higher than that in the control group (P < 0.05). The A allele of rs3212986 was associated with increased ischemic stroke risk (OR = 1.287, 95% CI = 1.076-1.540, P = 0.006). The association between rs3212986 polymorphism and ischemic stroke susceptibility was found in both recessive (OR = 2.638, 95% CI = 1.744-3.989, P < 0.001) and additive models (OR = 1.309, 95% CI = 1.028-1.667, P = 0.031), respectively. Similar results were obtained in the recessive model (OR = 2.015, 95% CI = 1.087-3.704, P = 0.026) after adjusting for demographic information and other variables. Additionally, the level of ERCC1 mRNA in the CC/CA genotype was higher than that in the AA genotype (P < 0.05). Conclusion: It was suggested that the ERCC1 rs3212986 polymorphism was associated with ischemic stroke susceptibility in a Chinese Han population and that an A allele of rs3212986 was related to increased ischemic stroke risk. The altered ERCC1 expression level caused by the rs3212986 polymorphism might participate in the pathophysiological process of ischemic stroke.
ABSTRACT
Background: Few studies have directly investigated the differential expression of microRNAs (miRNAs) in head and neck squamous cell carcinoma (HNSCC) with low, medium, and high tobacco exposure. The purpose of this study is to screen the differentially expressed miRNAs and to investigate their clinical significance and potential biological mechanisms in the three groups of HNSCC. Methods: The datasets of HNSCC were obtained from The Cancer Genome Atlas (TCGA). The edgeR package was used to determine differentially expressed miRNAs and genes among the three groups of HNSCC. Statistical methods were applied to assess the clinical significance of miRNA and its correlation with genes. The correlation between gene expression and clinical characteristics was analyzed using weighted gene co-expression network analysis (WGCNA). Three online databases were used to predict the target genes of miRNAs. More importantly, qRT-PCR was employed to verify the differential expression of miRNAs and genes in our patients. Results: 32 differentially expressed miRNAs and 1,820 differentially expressed genes were found among the three groups of HNSCC. Patients with high expression of hsa-miR-499a had lower overall survival than the ones with low expression in high-tobacco exposed HNSCC. Cox regression analysis found that high expression of hsa-miR-499a and female were independent risk factors for prognosis in high-tobacco exposed HNSCC. Chi-square test found that hsa-miR-499a was associated with N stage in high-tobacco exposed HNSCC. WGCNA identified four gene modules associated with N stage in high-tobacco exposed HNSCC. Then three online databases were used to predict potential target genes for hsa-miR-499a, which were AEBP2 and ZNRF1. Pearson correlation analysis showed that hsa-miR-499a was negatively correlated with AEBP2 and ZNRF1. qRT-PCR supported bioinformatic results that hsa-miR-499a, AEBP2, and ZNRF1 were differentially expressed among the three groups of HNSCC in our patients. Conclusion: 32 differentially expressed miRNAs and 1,820 differentially expressed genes were successfully identified in HNSCC with low, medium, and high tobacco exposure. The patients with high expression of hsa-miR-499a had poor prognoses compared with patients with low expression in high-tobacco exposed HNSCC. Hsa-miR-499a was associated with N stage in high-tobacco exposed HNSCC. AEBP2 and ZNRF1 were the potential target genes of hsa-miR-499a.
ABSTRACT
OBJECTIVE: To determine whether regenerated hair cells in the basilar papilla of chickens are resistant to kanamycin monosulfate damage. DESIGN: Randomized controlled trial. SUBJECTS: Ninety newly hatched Roman chickens. INTERVENTION: Chickens were injected with kanamycin monosulfate (200 mg/kg/d) for 10, 13, 17, 20, 25, or 30 days. RESULTS: Scanning electron microscopy revealed that hair cells in the proximal 40% of the basilar papilla degenerated and disappeared after 10 days of kanamycin treatment. Following this, hair cell regeneration and repair was apparent. Regeneration and maturation of hair cells within 20 days in chickens that received treatment for 20 days were similar to those in chickens that were treated for 10 days followed by 10 days of recovery. After 25 days of treatment, many regenerated hair cells of mature appearance were reinjured. Regenerated hair cells of immature appearance were not damaged. The auditory brainstem response assay showed that the loss and recovery thresholds in chickens treated with kanamycin for 20 days were similar to those in chickens treated for 10 days followed by 10 days of recovery. There was a loss of auditory brainstem response thresholds in chickens that were treated with kanamycin for more than 20 days. CONCLUSION: The immature regenerated hair cells in the basilar papilla of chickens are resistant to kanamycin ototoxic effects; however, this resistance is not seen in mature hair cells following prolonged kanamycin exposure.
