consultation; and (iii) establish a short-term web-based followup to define drug efficacy and adapt treatment accordingly. Thus, in this particular situation the diagnosis of AIH may be given without histology, if typical biochemical and serological results are followed by a convincing treatment response. Prove of the diagnosis can be undertaken later, either by a relapse upon therapy reduction, or a follow-up liver biopsy when conditions are safer. As already reported in China, 8 advanced liver cirrhosis and decompensated patients can be monitored with a webbased system and all non-urgent medical visits should be postponed until the emergency is over. Urgent procedures (i.e. paracentesis) should be organised using a COVID-19-free path in the hospital, another COVID-19-free facility or home care. Finally, we recommend strict adherence to standard social distancing protocols and social isolation and emphasise, in cirrhotic patients, the importance of vaccination for Streptococcus pneumoniae and seasonal flu and of reinforcing social distancing measures. Further data are needed in order to demonstrate the real impact of COVID-19 infection in immunocompromised patients. Until then, and while vaccination is not available, we suggest continuing a cautious approach during low-level seasonal persistence of COVID-19 in the years to come.Although we cannot currently evaluate the efficacy of our management protocol, we believe this framework might be a useful tool for management of AILD for the time being.

Double cortin-like kinase 1 (DCLK1) plays important roles during the epithelial-mesenchymal transition (EMT) process in human colorectal cancer (CRC). However, the role of DCLK1 in regulating the EMT of CRC is still poorly understood. In this study, we report evidence that DCLK1 acts as a potent oncogene to drive its extremely malignant character of EMT in an NF-κB-dependent manner in CRC cells. Mechanistic investigations showed that DCLK1 induced the NF-κBp65 subunit expression through the PI3K/Akt/Sp1 axis and activated NF-κBp65 through the PI3K/Akt/IκBα pathway during the EMT of CRC cells. Moreover, we found that silencing the expression of DCLK1 inhibited the invasion and metastasis of CRC cells in vivo. Collectively, our findings identify DCLK1 as a pivotal regulator of an EMT axis in CRC, thus implicating DCLK1 as a potential therapeutic target for CRC metastasis.

Emerging evidence has revealed that miRNAs could upregulate the expression levels of target genes. However, the molecular mechanism underlying upregulation of targets mediated by miRNAs remains unclear. In this study, we found a novel miRNA named MIR-G-1 by GRSF1-RNA immunoprecipitation (RIP)-deep sequencing, which could directly target and upregulate LMNB1 and TMED5 in a GRSF1dependent manner in cervical cancer cells. In addition, upregulated MIR-G-1 in cervical cancer promoted a malignant phenotype in vitro and in vivo. TMED5 could interact with WNT7B and thus activated the canonical WNT-CTNNB1/β-catenin signaling pathway. MIR-G-1 mediated the activation of this pathway. Furthermore, MIR-G-1 promoted serum starvation-induced nuclear macroautophagy/autophagy, and accelerated taxol (TAX)-induced DNA-damage repair in cervical cancer cells. Collectively, these findings may provide a new insight into the upregulation mechanism and nuclear autophagy mediated by miRNAs and provide a potential biomarker for cervical cancer.

BackgroundMicroRNAs (miRNAs) play important roles in cancer initiation and development. Epithelial–mesenchymal transition (EMT) is a form of cellular plasticity that is critical for embryonic development and metastasis. The purpose of the study was to determine the function and mechanism of miR-484 in initiation and development of cervical cancer (CC).MethodsWe determined the expression levels of miR-484 in cervical cancer tissues and cell lines with RT-qPCR. Prediction algorithms and EGFP reporter assay were performed to evaluate the targets for miR-484. MTT assay, colony formation assay, flow cytometric analysis, transwell cell migration and invasion assays, and detection of EMT markers were employed to investigate the roles of miR-484 and the targets in regulation of cell proliferation and EMT process. We also used rescue experiments to confirm the effect of miR-484 on CC cells through directly regulating the expression of its targets.ResultsFirstly we found miR-484 was down-regulated in cervical cancer tissues and cell lines compared with their matched non-cancerous tissues or normal cervical keratinocytes cells. Further studies revealed that overexpression of miR-484 suppressed the cell proliferation, while exacerbates apoptosis. Besides, miR-484 suppressed cellular migration, invasion and EMT process of CC cells. EGFP reporter assay showed that miR-484 binds to ZEB1 and SMAD2 3′UTR region and reduced their expression. The expression of miR-484 had reverse correlation with SMAD2/ZEB1, and SMAD2/ZEB1 had positive correlation with each other in cervical cancer tissues and cell lines. Furthermore, the ectopic expression of ZEB1 or SMAD2 could rescue the malignancies suppressed by miR-484, suggesting that miR-484 down-regulates ZEB1 and SMAD2 to repress tumorigenic activities.ConclusionWe found miR-484 inhibits cell proliferation and the EMT process by targeting both ZEB1 and SMAD2 genes and functions as a tumor suppressor, which may served as potential biomarkers for cervical cancer.

Three oxidative routes: Two cytochrome P450‐like mono‐oxygenases cooperate in the biosynthesis of nosiheptide (Nos): NosB catalyzes hydroxylation of the Glu6 γ‐position, whereas NosC hydroxylates the Pyr3 position, thus enabling cleavage of the bis‐Dha tail by NosA. Combining the polysubstrate specificity of NosB and NosC and the function of NosA generates three oxidative routes in nosiheptide maturation.