ABSTRACT
The three-dimensional (3D) conformation of chromatin is integral to the precise regulation of gene expression. The 3D genome and genomic variations in non-alcoholic fatty liver disease (NAFLD) are largely unknown, despite their key roles in cellular function and physiological processes. High-throughput chromosome conformation capture (Hi-C), Nanopore sequencing, and RNA-sequencing (RNA-seq) assays were performed on the liver of normal and NAFLD mice. A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments, topologically associated domains (TADs), and chromatin loops by Hi-C, and whole genome sequencing identifying structural variations (SVs) and copy number variations (CNVs) by Nanopore sequencing. We identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements, between normal and NAFLD mice, and revealed gene dysregulation frequently accompanied by these variations. Candidate target genes were identified in NAFLD, impacted by genetic rearrangements and spatial organization disruption. Our data provide a high-resolution 3D genome interaction resource for NAFLD investigations, revealed the relationship among genetic rearrangements, spatial organization disruption, and gene regulation, and identified candidate genes associated with these variations implicated in the pathogenesis of NAFLD. The newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.
ABSTRACT
Objective To investigate the effect of the aqueous extracts from Dioscorea nipponica Makino (AEDN) against the carbon tetrachloride (CCl4)-induced mice acute liver injury by regulating TLR4/MyD88 signal pathway.Methods 60 mice were randomly divided into control group, model group, low, medium and high dose AEDN groups according to radom number table with 10 mice in each group. Mice in low, medium and high dose AEDN groups were adiminstrated with 50, 100 and 200 mg/kg AEDN, in control and model groups were adiminstrated with solvent once a day for 7 consecutive days. Two hours after the last administration, mice were intraperitoneal injected with with 0.3% CCl4 olive oil solution to induce acute liver injury model, except for the mice in control group. Twenty-four hours after injection, the expressions of TLR4, MyD88 and NF-κB in liver tissue were evaluated by Western blot, mRNA levels were evaluated by PCR, and the AST and ALT levels in serum were also detected.Results Compared with model group, the serum AST (98.00 ± 17.75 U/L, 57.49 ± 9.66 U/L, 39.60 ± 9.49 U/Lvs. 113.40 ± 9.71 U/L) and ALT levels (76.00 ± 14.73 U/L, 50.70 ± 9.35 U/L, 35.25 ± 9.93 U/Lvs. 95.42 ± 11.64 U/L) were significantly decreased in low, medium and high dose AEDN groups (P<0.01); MyD88 (0.67 ± 0.21vs. 1.74 ± 0.42), NF-κB p65 (0.51 ± 0.09vs. 1.76 ± 0.31) and TLR4 (0.97 ± 0.25vs. 2.99 ± 0.72) levels were down-regulated in high dose AEDN group (P<0.01); the mRNA levels of IL-6 (2.22 ± 0.25, 1.76 ± 0.31vs. 5.20 ± 0.60), IL-1β (1.96 ± 0.35, 1.47 ± 0.23vs. 7.37 ± 0.99)、TNF-α (2.06 ± 0.25, 1.34 ± 0.33vs. 2.98 ± 0.50) in medium and high dose AEDN groups significantly decresed (P<0.01).Conclusions The AEDN has protective effect against CCl4-induced acute liver injury in mice via adjusting TLR4/MyD88 signal pathway.
ABSTRACT
Acute kidney injury (AKI), a common clinical dis-ease, is one complex pathophysiological process. In this review paper, the relationship and the molecular mechanisms of ische-mia-reperfusion, major surgery, rhabdomyolysis, pus sepsis and drug-induced renal toxicity associated with AKI were comprehen-sively reviewed. In addition, the prevention and treatment of AKI by Chinese medicine and the effective components were also reviewed. Therefore, our review aims to provide valuable infor-mation for treatment of AKI, and also for exploration of innova-tive new drugs.