Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3ß pathway.

OBJECTIVE: Acetaminophen (APAP) is one of the world's popular and safe painkillers, and overdose can cause severe liver damage and even acute liver failure. The effect and mechanism of the xanthohumol on acetaminophen-induced hepatotoxicity remains unclear. METHODS: The hepatoprotective effects of xanthohumol were studied using APAP-induced HepG2 cells and acute liver injury of mouse, seperately. RESULTS: In vitro, xanthohumol inhibited H2O2- and acetaminophen-induced cytotoxicity and oxidative stress. Xanthohumol up-regulated the expression of Nrf2. Further mechanistic studies showed that xanthohumol triggered Nrf2 activation via the AMPK/Akt/GSK3ß pathway to exert a cytoprotective effect. In vivo, xanthohumol significantly ameliorated acetaminophen-induced mortality, the elevation of ALT and AST, GSH depletion, MDA formation and histopathological changes. Xanthohumol effectively suppressed the phosphorylation and mitochondrial translocation of JNK, mitochondrial translocation of Bax, the activation o cytochrome c, AIF secretion and Caspase-3. In vivo, xanthohumol increased Nrf2 nuclear transcription and AMPK, Akt and GSK3ß phosphorylation in vivo. In addition, whether xanthohumol protected against acetaminophen-induced liver injury in Nrf2 knockout mice has not been illustated. CONCLUSION: Thus, xanthohumol exerted a hepatoprotective effect by inhibiting oxidative stress and mitochondrial dysfunction through the AMPK/Akt/GSK3ß/Nrf2 antioxidant pathway.

Long non-coding RNA LINC01963 inhibits progression of pancreatic carcinoma by targeting miR-641/TMEFF2.

PURPOSE: The aim of this study was to research the molecular mechanism of lncRNA LINC01963 in pancreatic carcinoma progression. METHODS: Total 67 pancreatic cancer patients diagnosed and undergoing pancreatic cancer surgery in our hospital from April 2018 to April 2019 were included in this study. Pancreatic cancer cell lines including PANC-1, CFPAC-1, BxPC-3, SW1990 and AsPC1 were used. Based on bioinformatics information, pIRES2-LINC01963 plasmid, siLINC01963, miRNA mimics, miRNA inhibitor or siTMEFF2 were transfected. qRT-PCR and western blot were used to detect the expression of LINC01963, miR-641 and TMEFF2. CCK8 and Colony formation assay were processed for proliferation. Flow Cytometry Assay was processed to detect cell cycle and apoptosis. Transwell experiment was undertaken for invasion and migration. Luciferase assay and RNA Immunoprecipitation assay were used to verify the binding site among LINC01963, miR-641 and TMEFF2. Tumorigenic experiment was processed to confirm the above mechanisms in vivo. RESULTS: lncRNA LINC01963 was confirmed to be lower expressed in pancreatic carcinoma tissues and cell lines. By up-regulating the expression of lncRNA LINC01963 in pancreatic carcinoma cell lines, colony number, cell cycle, proliferation and invasion were inhibited, while apoptosis was improved. More importantly, shLINC01963 could improve development of tumor in vivo. Besides, lncRNA LINC01963 negatively regulated the expression of miR-641, while miR-641 negatively targeted TMEFF2. Both miR-641 mimic and siTMEFF2 could reverse the effects of lncRNA LINC01963 overexpression in vitro. CONCLUSIONS: Long non-coding RNA LINC01963 inhibits progression of pancreatic carcinoma by targeting miR-641/TMEFF2.

[Molecular Epidemiology of Echovirus 30 in Longyan City, Fujian, China, 2011～2014].

We studied the molecular epidemiology of echovirus 30 in sporadic cases of viral encephalitis in Longyan City, Fujian, China, from 2011 to 2014.Specimens of cerebrospinal fluid from patients diagnosed with viral encephalitis or infection of the central nervous system were collected. Viruses were isolated by cell culture. Identification of the echovirus 30 serotype and genetic analyses were undertaken. Amplification of virus protein(VP)-1gene sequences was done by reverse transcription-polymerase chain reaction. A total of 168 strains of enterovirus were isolated in 608 cases from 2011 to 2014,of which 60 strains were echovirus 30.The epidemic "peak" of echovirus 30 was from June to August. The age range of patients was wide, with 65% of cases under 10 years of age. Clinical manifestations were pyrexia, headache and vomiting.Cerebrospinal fluid was clear, and the number of cells and protein was increased. The epidemic strains in Longyan City from 2011 to 2014belonged to the "h" genotype, and there were two transmission chains. Compared with the viral encephalitis strains from the outbreak in Fujian Province in 2011,they were highly homologous, but a new amino-acid variation of VP1 protein I 120 V was found in Longyan City strains from 2014.The viral encephalitis strains from the outbreak in Fujian Province in 2011 were present in Longyan City strains, and two transmission chains are still circulating,but there were new mutations in the virus strains from 2014.Continuous monitoring will aid:(i)early detection of viral variants that may accumulate;(ii)assessment of the risk of epidemics.

[Genetic analysis of Echovirus 11 isolated from patients with viral encephalitis in Longyan, China].

This study aimed to analyse the genetically characterize isolates of Echovirus 11 from Longyan City,Fujian Province,and to reveal their genetic relationships with other isolates from China and abroad. Cerebrospinal fluid specimens from patients diagnosed with viral encephalitis or central nervous system (CNS) infections were collected from Longyan First Hospital between January and December 2011. Seven Echo11 strains were isolated and identified using the RIMV serum panel. The entire VP1 coding regions of four strains were sequenced and typed as Echo11 by an online blast program and,subsequently, phylogenet- ic analyses of the VP1 sequences of these stains and others published on GenBank were conducted. There were 600 nucleotides (nt) in each complete VP1 coding region that encoded 200 amino acids (aa). Among those four Echo11 strains, the sequence identities of nt and aa were 100% and 99%-100% respectively. And phylogenetic analyses indicate belong to subtype DS, the homology compared with DS strain (GU393713) were 93% (nt) and 99% (aa). The sequence identities for the nt and aa were 75%-76% and 90%, respectively, between the current isolates from Longyan and the Gregory prototype strain found in 1953. The sequence identity of nt and aa between the Longyan virus strains and the domestic Shandong strains isolated in 2010 were lower, at 74% and 88%-89%, respectively. However,the highest level of ho- mology was found when the Longyan strains were compared with the Netherlands strain (GU393773) found in 2007 (nt and aa identity: 94%-95% and 98%-99%, respectively). The relatively low levels of similarity between domestic isolates suggest that different transmission routes exist for Echo11 in mainland China.

[Analysis of genetic characteristics of ECHO6 virus isolated from an epidemic outbreak of encephalitis in Longyan, China].

This study aimed to analyze the etiology of the encephalitis outbreak in Longyan, Fujian Province, China in 2010, in order to provide valuable information for this prevention and control of this disease. Pathogens were confirmed from cerebrospinal fluid samples with fluorescent RT-PCR, virus isolation (RD cells), and neutralization tests. Then, the VP1 fragments or whole genome nucleotide sequences were determined for four virus strains using PCR. Homology was assessed using the MegAlign software, and a phylogenetic evolutionary tree was drawn using Mega 4.0 software. The results confirmed that the etiology of the outbreak was the ECHO6 intestinal virus, and the nucleotide sequence of the VP1 segment indicated that the C2 subtype was responsible. The genome sequence consisted of 7407 nucleotides, and resembled the genome of other ECHO and CoxB viruses with homology levels of 78.5%-87.3%. The encephalitis outbreak in Longyan in 2010 was caused by the ECHO6 C2 subtype intestinal virus, and its complete genome sequence length is similar to the standard strain (U16283) with a sequence homology of 80.4%.