AMPK-ERK/CARM1 Signaling Pathways Affect Autophagy of Hepatic Cells in Samples of Liver Cancer Patients.

Liver cancer is one of the most common malignant tumors, with the death rate ranking fourth among all types of cancer. Over the past few decades, several studies have reported that liver tumorigenesis is associated with dysfunction in autophagy. However, the detailed mechanism remains unclear. In this paper, we used tissue micro-array (TMA) of liver cancer to detect proteins associated with the regulation of autophagic signaling in non-cancerous and cancerous regions by immunohistochemical staining. Those proteins contained 4-HNE, p-AMPK, Erk1/2, p-Erk1/2, CARM1, TFEB, LAMP1, and p62. According to the degrees of tumor differentiation in patients (well differentiated group vs. moderately and poorly differentiated group), we analyzed each protein's expression in the ratio of the "cancerous region/non-cancerous region" in two groups. Current data showed that there were AMPK-ERK/CARM1 autophagic signaling pathways during the formation of liver cancer. The above-mentioned changes in signals indicated an upregulation of autophagy in cancerous regions, which means overactivated autophagy plays an important role in liver cancer.

Anti-inflammatory and antinociceptive effects of active ingredients in the essential oils from Gynura procumbens, a traditional medicine and a new and popular food material.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura procumbens is applied topically for the treatment of traumatic injuries in South China. MATERIALS AND METHODS: This study was conducted to identify the active ingredients in the essential oils from Gynura procumbens (GPEO) by Gas Chromatography-Mass Spectrometer (GC-MS) and to elucidate the mechanisms underlying the anti-inflammatory and antinociceptive effects in vivo and in vitro. RESULTS: A reduction in dswelling and pain were observed in mice treated with GPEO or its active ingredients (α-pinene, 3-carene, and limonene) compared with mice treated with a solvent control. GPEO or its three active ingredients had potent pharmacological effects on COX-2 overexpression and LPS-induced migration of Raw264.7 macrophages. All three ingredients inhibited nociceptive stimulus-induced inflammatory infiltrates and COX-2 overexpression, which could be responsible for the anti-inflammatory effect of GPEO. However, only 3-carene produced an antinociceptive effect. CONCLUSION: Consistent with the traditional usage in Southern China, GPEO may serve as a promising potent external therapeutic agent for the treatment of chronic pain.

Extract of the Blood Circulation-Promoting Recipe-84 Can Protect Rat Retinas by Inhibiting the ß-Catenin Signaling Pathway.

Extract of the Blood Circulation-Promoting Recipe (EBR-84) from the Chinese Herbal medicine "Blood Circulation Promoting Recipe" could retard retinopathy development. This study investigated whether EBR-84 protects retinas by inhibiting the ß-catenin pathway using a rat model of retinopathy and a retinal ganglion cell 5 (RGC-5) cell death model. RGC death was induced by either N-methyl-d-aspartic acid (NMDA) or TWS119 (an activator of the ß-catenin pathway). After the corresponding treatment with EBR-84, RGC death and the protein expression levels of ß-catenin, cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) in rat retinas were examined. ß-Catenin accumulated in the retinal ganglion cell layer (GCL) of NMDA-treated rats. EBR-84 (3.9, 7.8, and 15.6 g/kg) significantly attenuated the NMDA-induced RGC loss accompanying the reduction of ß-catenin expression. Moreover, the expression levels of COX-2 and VEGF were decreased by EBR-84 in a dose-dependent manner. For the TWS119-treated rats, EBR-84 also ameliorated RGC loss and lowered the expression levels of ß-catenin, COX-2, and VEGF. In vitro, EBR-84 increased the viability of NMDA-treated RGC-5 while decreased ß-catenin expression. In conclusion, EBR-84 retarded ratretinopathy, and the ß-catenin signaling pathway played an important role during this protective process.

Chronic high-dosage fish oil exacerbates gut-liver axis injury in alcoholic steatohepatitis in mice: the roles of endotoxin and IL-4 in Kupffer cell polarization imbalance.

In the present study, intestinal tight junctions (TJs) and Kupffer cell polarization were investigated in an alcoholic steatohepatitis (ASH) mouse model to uncover the potential side effects of overexposure to fish oil or omega-3 fatty acids. The mice were fed ad libitum with a liquid diet containing ethanol and fish oil. In the meantime, ethanol was given every 5-7 days by gavage to simulate binge drinking. After the 7th binge, steatosis, necrosis, inflammatory infiltration, and bridging fibrosis were observed in the liver by histological staining. After the 13th binge, the inducers, markers and other downstream genes/proteins of the Kupffer cell M1/M2 phenotype in the liver, serum, and small intestine were analysed. The results suggested that a chronic high dosage of fish oil alone reduced the mRNA levels of most genes tested and showed a tendency to damage the intestinal zonula occludens-1 localization and reduce the number of M2 Kupffer cells. Meanwhile, the combination of fish oil and ethanol damaged the intestinal TJs, resulting in an increased endotoxin level in the liver. Gut-derived endotoxin polarized Kupffer cells to the M1 phenotype, whereas the number of cells with the M2 phenotype (markers: CD163 and CD206) was decreased. Interleukin-4 (IL-4), an M2 Kupffer cell inducer, was also decreased. Moreover, in vitro experiments showed that IL-4 reversed eicosapentaenoic acid-induced CD163 and CD206 mRNA suppression in RAW 264.7 cells. Overall, our results showed that a chronic high dosage of fish oil exacerbated gut-liver axis injury in alcoholic liver disease in mice, and endotoxin/IL-4-induced Kupffer cell polarization imbalance might play an important role in that process.