No abstract

Currently, it is not entirely clear whether hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of COX-2 expression and epithelial-to-mesenchymal transition (EMT), and whether these events affect the prognosis of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE). In this report the relationship between HIF-1α and COX-2 protein expression, EMT in tumor specimens from HCC patients after TACE surgery and the clinical significance of HIF-1α and COX-2 expression were analyzed using statistical approaches. HepG2 cells treated with CoCl2 was employed as a hypoxia cell model in vitro to study hypoxia-induced HIF-1α, COX-2 expression, and EMT alteration. The results showed that HIF-1α and COX-2 protein expression increased in HCC tissues after TACE surgery. Moreover, there was positive correlation between upregulation of HIF-1α and COX-2. Elevated expression of HIF-1α increased both Snail and Vimentin protein expression, while it reduced E-cadherin protein expression. It was further verified that hypoxia enhanced protein expression of HIF-1α and COX-2 in HepG2 cells treated with CoCl2. Upregulation of HIF-1α and COX-2, together with EMT alteration resulted in increased migration and invasion of HepG2 cells under hypoxia. In conclusion, TACE surgery results in aggravated hypoxia status, leading to increased HIF-1α protein expression in HCC tissue. To adapt to hypoxic environment, HIF-1α stimulates COX-2 protein expression and promotes EMT process in hepatocellular cancer cells, which enhances HCC invasion and metastasis, and might contribute to poor prognosis in HCC patients post TACE treatment.

The composition and activity of the gut microbiota depend on the host genome, nutrition, and lifestyle. Exercise and sodium butyrate (NaB) exert metabolic benefits in both mice and humans. However, the underlying mechanisms have not been fully elucidated. This study aimed to examine the effect of exercise training and dietary supplementation of butyrate on the composition of gut microbiota and whether the altered gut microbiota can stimulate differential production of short-chain fatty acids (SCFAs), which promote the expression of SESN2 and CRTC2 to improve metabolic health and protect against obesity. C57BL/6J mice were used to study the effect of exercise and high-fat diet (HFD) with or without NaB on gut microbiota. Bacterial communities were assayed in fecal samples using pyrosequencing of 16S rRNA gene amplicons. Western blot was performed using relevant antibodies to detect the protein expressions in liver and HepG2 cell extracts. Exercise and butyrate administration significantly reversed metabolic dysfunctions induced by HFD (P < 0.05). The number of Firmicutes and the proportion of Firmicutes to Bacteroidetes order were predominant in all HFD groups (P = 0.001). Exercise and butyrate supplementation significantly inhibited the relative abundance of lipopolysaccharide-producing phyla (P = 0.001). SESN2 and CRTC2 expression in the liver of mice were significantly increased after exercise (P < 0.05) and/or supplementation of butyrate (P < 0.05). Exercise enhances butyrate-producing fecal bacteria and increases butyrate production and consequently improves lipid metabolism through the butyrate-SESN2/CRTC2 pathway. Excess butyrate may reduce the proportion of probiotics and reverse the metabolic effects.

A path in an edge-colored graph G, where adjacent edges may have the same color, is called a rainbow path if no two edges of the path are colored the same. The rainbow connection number rc(G) of G is the minimum integer i for which there exists an i-edge-coloring of G such that every two distinct vertices of G are connected by a rainbow path. It is known that for a graph G with diameter 2, to determine rc(G) is NP-hard. So, it is interesting to know the best upper bound of rc(G) for such a graph G. In this paper, we show that rc(G) ≤ 5 if G is a bridgeless graph with diameter 2, and that rc(G) ≤ k + 2 if G is a connected graph of diameter 2 with k bridges, where k ≥ 1.

Abnormal glucose metabolism induces various metabolic disorders such as insulin resistance and type 2 diabetes. Regular exercise improved glucose uptake and enhanced glucose oxidation by increasing GLUT4 transcription in skeletal muscle. However, the regulatory mechanisms of GLUT4 transcription in response to exercise are poorly understood. AMPK is a sensor of exercise and upstream kinase of class II HDACs that act as transcriptional repressors. We used 6-week treadmill exercise or one single-bout exercise wild type or AMPKα2 C57BL/6J mice to explore how HDACs regulate GLUT4 transcription and the underlying molecular mechanisms mediated by AMPK in the physiologic process of exercise. We demonstrate that regular physical exercise significantly enhanced GLUT4 transcription by inactivating HDAC4/5 in skeletal muscle by ChIP experiment. HDAC4 coordinately regulated with HDAC5 represses transcriptional activity of GLUT4 promoter in C2C12 myotubes by Luciferase assay. If either HDAC4 or HDAC5 is silenced via RNAi technology, the functional compensation by the other will occur. In addition, a single-bout of exercise decreased HDAC4/5 activity in skeletal muscle of wild type but not in AMPKα2 mice, suggesting an AMPKα2-dependent manner. Those findings provide new insight into the mechanisms responsible for AMPKα2-dependent regulation of GLUT4 transcription after exercise.

No abstract

It is well known that neural stem cells (NSC) could promote the repairment after spinal cord injury, but the underlying mechanism remains to be elucidated. This study showed that the transplantation of NSC significantly improved hindlimb locomotor functions in adult rats subjected to transection of the spinal cord. Biotin dextran amine tracing together with the stimulus experiment in motor sensory area showed that little CST regeneration existed and functional synaptic formation in the injury site. Immunocytochemistry and RT-PCR demonstrated the secretion of NGF, BDNF, and NT-3 by NSC in vitro and in vivo, respectively. However, only mRNA expression of BDNF and NT-3 but not NGF in injury segment following NSC transplantation was upregulated remarkably, while caspase-3, a crucial apoptosis gene, was downregulated simultaneously. These provided us a clue that the functional recovery was correlated with the regulation of BDNF, NT-3, and caspase-3 in spinal cord transected rats following NSC transplantation.

Following spinal cord injury (SCI), limit spontaneous functional recovery often emerged. However, the neuronal mechanisms associated with this phenomenon still remains obscure. By using proteomics analysis, endoplasmic reticulum protein 29 (ERp29) was discovered to increase in the motor cortexes of spinal cord transection (SCT) rats for 28 days post-operation (dpo) compared with in 14dpo. Then, the change in the expression of ERp29 was confirmed by using reverse transcription polymerase chain reaction (RT-PCR) and Western blot. To determine the role of ERp29 in the recovery of locomotor functions following SCT, lentiviral vectors were used to up- and downregulate the expression level of ERp29. Here, we found that cortical neurons in vitro with high level of ERp29 expression exhibited a significant proliferation, characterized by smaller size of soma and more extensive axon outgrowth, compared with neurons used as control, while ERp29 silence got the opposite results. In vivo, Lentivirus was inject into the cerebral cortex following SCT at thoracic level 10, which resulted in an increase number of neuronal nuclei(NeuN)-positive cells and less apoptotic cells. Moreover, increased PKC-γ immunoreactivity density was also found in the spinal cord T9 level compared with control rats. This was associated with a great functional improvement, indicated by Basso, Beattie, Bresnahan (BBB) locomotor rating scale. Lastly, we verified that ERp29 acts as a regulator by regulating a group of genes related with cell survival and apoptosis, involving in caspase and Erk, but not PI3K. Our findings showed that ERp29 can improve locomotor function by promoting neuronal survival and axonal regeneration in SCT rats via caspase and Erk signal pathway.