RNA editing in response to COVID-19 vaccines: unveiling dynamic epigenetic regulation of host immunity.

Background: COVID-19 vaccines are crucial for reducing the threat and burden of the pandemic on global public health, yet the epigenetic, especially RNA editing in response to the vaccines remains unelucidated. Results: Our current study performed an epitranscriptomic analysis of RNA-Seq data of 260 blood samples from 102 healthy and SARS-CoV-2 naïve individuals receiving different doses of the COVID-19 vaccine and revealed dynamic, transcriptome-wide adenosine to inosine (A-to-I) RNA editing changes in response to COVID-19 vaccines (RNA editing in response to COVID-19 vaccines). 5592 differential RNA editing (DRE) sites in 1820 genes were identified, with most of them showing up-regulated RNA editing and correlated with increased expression of edited genes. These deferentially edited genes were primarily involved in immune- and virus-related gene functions and pathways. Differential ADAR expression probably contributed to RNA editing in response to COVID-19 vaccines. One of the most significant DRE in RNA editing in response to COVID-19 vaccines was in apolipoprotein L6 (APOL6) 3' UTR, which positively correlated with its up-regulated expression. In addition, recoded key antiviral and immune-related proteins such as IFI30 and GBP1 recoded by missense editing was observed as an essential component of RNA editing in response to COVID-19 vaccines. Furthermore, both RNA editing in response to COVID-19 vaccines and its functions dynamically depended on the number of vaccine doses. Conclusion: Our results thus underscored the potential impact of blood RNA editing in response to COVID-19 vaccines on the host's molecular immune system.

Hippocampal adenosine-to-inosine RNA editing in sepsis: dynamic changes and influencing factors.

Sepsis-associated encephalopathy is a diffuse brain dysfunction secondary to infection. It has been established that factors such as age and sex can significantly contribute to the development of sepsis-associated encephalopathy. Our recent study implicated a possible link between adenosine-to-inosine RNA editing and sepsis-associated encephalopathy, yet the dynamics of adenosine-to-inosine RNA editing during sepsis-associated encephalopathy and how it could be influenced by factors such as age, sex and antidepressants remain uninvestigated. Our current study analysed and validated transcriptome-wide changes in adenosine-to-inosine RNA editing in the hippocampus of different septic mouse models. Seventy-four sites in 64 genes showed significant differential RNA editing over time in septic mice induced by caecal ligation and perforation. The differential RNA editing might contribute to the RNA expression regulation of the edited genes, with 42.2% differentially expressed. These differentially edited genes, especially those with missense editing, such as glutamate receptor, ionotropic, kainate 2 (Grik2, p.M620V), filamin A (Flna, p.S2331G) and capicua transcriptional repressor (Cic, p.E2270G), were mainly involved in abnormal social behaviour and neurodevelopmental and psychiatric disorders. Significant effects of age and sex were also observed on sepsis-associated RNA editing. Further comparison highlighted 40 common differential RNA editing sites that caecal ligation and perforation-induced and lipopolysaccharide-induced septic mouse models shared. Interestingly, these findings demonstrate temporal dynamics of adenosine-to-inosine RNA editing in the mouse hippocampus during sepsis, add to the understanding of age and sex differences in the disease and underscore the role of the epigenetic process in sepsis-associated encephalopathy.

Effect of clinical application of anti-CD38 and anti-CD47 monoclonal antibodies on blood group detection and transfusion therapy and treatment.

BACKGROUND: To investigate the effect of anti-CD38 monoclonal antibodies (mAb) (daratumumab, DARA) and anti-CD47 mAb combined with azacytidine on blood transfusion compatibility tests, transfusion effects in the treatment of multiple myeloma or acute myeloid leukemia and the corresponding management strategy. MATERIALS AND METHODS: Among the 19 patients who were treated with DARA and anti-CD47 mAb, 4 patients with cross matching incompatibility were selected. The ABO blood group, the Rh blood group, irregular antibody screening and direct antiglobulin test (DAT) and cross matching testing were performed before and after the application of mAbs using serological methods. Then, irregular antibody screening and microcolumn gel cross matching tests were performed with donor and recipient erythrocytes and serum treated with DL-dithiothreitol (DTT) and Immucor kit, respectively. The transfusion effect was monitored. RESULTS: 21.05% (4/19) patients had mismatched cross-matching results after mAb treatment. The agglutination intensity of irregular antibody screening tests (3 + ∼ 4 +) after anti-CD47 mAb was higher than that (1 + ∼ 2 +) after DARA. In the DARA group, treating RBCs with 0.2 mol L-1 DTT eliminated the DARA interference with antibody screening. In the anti-CD47 mAb group, the antibody screening, cross-matching test and DAT had been strongly interfered, and using Immucor kit eliminated the interference with antibody screening testing. There was no difference in the transfusion effect. CONCLUSION: The application of mAb drugs led to incompatibility of cross matching tests, and the transfusion effect was not affected.

Inhibition of GLUTs by WZB117 mediates apoptosis in blood-stage Plasmodium parasites by breaking redox balance.

Like tumour cells, during intraerythrocytic stage, Plasmodium-infected erythrocytes rely completely on glucose absorption from the blood circulation for energy metabolism. Glucose is taken up by glucose transporter 1 (GLUT1) on human red blood cells (RBCs) and glucose transporter 4 (GLUT4) on rodent RBCs. Blood-stage parasites grow rapidly; therefore, infected red blood cells (iRBCs) need much more glucose for energy. In previous study, WZB117 (2-fluoro-6-(m-hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits GLUT1 by binding the exofacial sugar-binding site and inhibits the insulin-sensitive GLUT4 with greater potency than its inhibition of either GLUT1 or GLUT3. In our study, WZB117 effectively inhibit the growth of blood-stage parasites. Mechanistically, WZB117 inhibited the activity of GLUTs and perturbed the glycolysis. Therefore, decreasing the glucose level increased the redox oxidative species (ROS) level and induced oxidative stress and apoptosis. The spleen can more easily clear apoptopic iRBCs than nonapoptotic iRBCs, effectively relieving hepatosplenomegaly. These findings provide important insights into the crucial role of glucose transporters (GLUTs) in Plasmodium glucose uptake during intra-erythrocytic stage, as the inhibition of GLUTs block Plasmodium infection during the erythrocytic stage.