Objective To explore the oxidation stress effects of nitrogen monoxide (NO) on rats' hepatic fibrosis induced by carbon tetrachloride (CCl_4). Methods Thirty-four male Wistar rats were subcutaneously given CCl_4 to induce hepatic fibrosis model. Six additional rats were chosen to serve as control group. Histological sections of liver of the animals were stained by H & E and Massons staining. NO in serum, malon-dialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue were determined. Results At 7th week, grade 2 or 3 of hepatic fibrosis was reproduced, in which fibrous tissue formed fibrous septa, around the portal areas stretching into hepatic lobules. The structure of the hepatic lobules was intact or disarranged, but there was no signs of cirrhosis. There was moderate fatty change and vacuolar degeneration of heputocytes. The level of serum NO increased significantly (152.8?12.30?mol/L vs. 11.03?1.95?mol/L, P

Objective To investigate the effect of lamivudine (LAM) on serum interferon (IFN)-γ and interleukin (IL)-4 levels in patients with chronic hepatitis B(CHB). Methods Serum IFN-γ and IL-4 levels were measured with enzyme-linked immunosorbent assay (ELISA) in 66 CHB patients at baseline and 3, 6, 9 and 12 months after LAM treatment respectively. And 20 healthy volunteers served as healthy control. The comparision of pretreatment and post-treatment was done using t test and numberation data were analyzed by non parametric rank sum test. Results In HBeAg positive patients, the serum level of IFN-γ was (21.03±4.44) ng/L in complete response group, which was higher than partial response group [(13.85±3.92) ng/L] and non-response group [(10.63± 3.11) ng/L] (t=7.56,t=11.87, both P<0.01). Take that IFN-γ is 15.66 ng/L as boundry patients with high baseline IFN-γ level showed much higher complete response rate (31.0% vs 8.7%, x2 =8.391, P<0.01) and lower non-response rate (13.8% vs 52.2%,x2=4. 256, P<0.01) than those with low baseline IFN-γ levels. After LAM treatment, the IFN-γ/IL-4 ratios in complete response patients were approximate or even higher than those in healthy group, whereas the IFN-γ/ IL-4 ratios of patients with partial response and non response were lower than those in healthy group. In HBeAg negative patients, the IFN-γ/IL-4 ratios increased slowly but didn't reach the same levels of healthy group. Conclusions It is suggested that LAM treatment can increase IFN-γ release and reduce IL-4 release in CHB patients. The response type to LAM therapy is associated with the recovery of T helper cell (Th) 1/Th2 balance post-treatment and pretreatment IFN-γ levels.

Genome-wide association studies (GWASs) are the most widely used method to identify genetic risk loci associated with orofacial clefts (OFC). However, despite the increasing size of cohort, GWASs are still insufficient to detect all the heritability, suggesting there are more associations under the current stringent statistical threshold. In this study, we obtained an integrated epigenomic dataset based on the chromatin conformation of a human oral epithelial cell line (HIOEC) using RNA-seq, ATAC-seq, H3K27ac ChIP-seq, and DLO Hi-C. Presumably, this epigenomic dataset could reveal the missing functional variants located in the oral epithelial cell active enhancers/promoters along with their risk target genes, despite relatively less-stringent statistical association with OFC. Taken a non-syndromic cleft palate only (NSCPO) GWAS data of the Chinese Han population as an example, 3664 SNPs that cannot reach the strict significance threshold were subjected to this functional identification pipeline. In total, 254 potential risk SNPs residing in active cis-regulatory elements interacting with 1 718 promoters of oral epithelium-expressed genes were screened. Gapped k-mer machine learning based on enhancers interacting with epithelium-expressed genes along with in vivo and in vitro reporter assays were employed as functional validation. Among all the potential SNPs, we chose and confirmed that the risk alleles of rs560789 and rs174570 reduced the epithelial-specific enhancer activity by preventing the binding of transcription factors related to epithelial development. In summary, we established chromatin conformation datasets of human oral epithelial cells and provided a framework for testing and understanding how regulatory variants impart risk for clefts.
Chromatin ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Epithelium ; Genome-Wide Association Study ; Humans