Latest Issue
Issue 9 ， 2022
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Biomarkers in oral immunotherapy
Abstract：Food allergy (FA) is a global health problem that affects a large population, and thus effective treatment is highly desirable. Oral immunotherapy (OIT) has been showing reasonable efficacy and favorable safety in most FA subjects. Dependable biomarkers are needed for treatment assessment and outcome prediction during OIT. Several immunological indicators have been used as biomarkers in OIT, such as skin prick tests, basophil and mast cell reactivity, T cell and B cell responses, allergen-specific antibody levels, and cytokines. Other novel indicators also could be potential biomarkers. In this review, we discuss and assess the application of various immunological indicators as biomarkers for OIT.Keywords：Food allergy;Oral immunotherapy;Biomarker;Immune tolerance;Desensitization- 62
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Published：2022-09-15
Review
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CircRNA.0007127 triggers apoptosis through the miR-513a-5p/CASP8 axis in K-562 cells
Abstract：BackgroundCircular RNAs (circRNAs) are covalently closed single-stranded RNAs with multiple biological functions. CircRNA.0007127 is derived from the carbon catabolite repression 4-negative on TATA-less (CCR4-NOT) complex subunit 2 (CNOT2), which was found to regulate tumor cell apoptosis through caspase pathway.MethodsPotential circRNA.0007127 target microRNAs (miRNAs) were analyzed by miRanda, TargetScan, and RNAhybrid software, and the miRNAs with binding sites for apoptosis-related genes were screened. The roles of circRNA.0007127 and its downstream target, microRNA (miR)-513a-5p, were validated by quantitative real-time polymerase chain reaction (qPCR), flow cytometry, mitochondrial membrane potential, immunofluorescence, western blot, and caspase-8 (CASP8) protein activity in vitro in H2O2-induced K-562 cells. The circRNA.0007127‒miR-513a-5p and CASP8‒miR-513a-5p interactions were verified by luciferase reporter assays.ResultsSilencing circRNA.0007127 decreased cell apoptosis by inhibiting CASP8 pathway activation in K-562 cells. Compared with the control group, the expression of CASP8 was reduced by 50% and the 43-kD fragment of CASP8 protein was significantly reduced (P≤0.05). The luciferase reporting assay showed that circRNA.0007127 combined with miR-513a-5p or CASP8, with extremely significant differences (P≤0.001). The overexpression of miR-513a-5p inhibited the gene expression level of CASP8 in a human myeloid leukemia cell model (75% change) and the level of a 43-kD fragment of CASP8 protein (P≤0.01). The rescue experiment showed that cotransfection with circRNA.0007127 small-interfering RNA (siRNA) and the miR-513a-5p inhibitor increased CASP8 gene expression and the apoptosis rate, suggesting that the miR-513a-5p inhibitor is a circRNA.0007127 siRNA antagonist.ConclusionsCircRNA.0007127 regulates K-562 cell apoptosis through the miR-513a-5p/CASP8 axis, which can serve as a novel powerful molecular target for K-562 cells.Keywords：CircRNA.0007127;miR-513a-5p;Caspase-8 (CASP8);Apoptosis;K-562 cells- 100
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Published：2022-09-15 -
Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level
Abstract：The mechanisms underlying pregnancy complications caused by advanced maternal age (AMA) remain unclear. We analyzed the cellular signature and transcriptomes of human placentas in AMA women to elucidate these mechanisms. Placental tissues from two AMA women and two controls were used for single-cell RNA-sequencing (scRNA-seq). Controls consisted of AMA women who did not experience any pregnancy complications and pregnant women below the age of 35 years without pregnancy complications. Trophoblast cells were obtained from the placentas of another six pregnant women (three AMA women and three controls), and in-vitro transwell assays were conducted to observe the cell invasion ability. Thirty additional samples (from 15 AMA women and 15 controls) were analyzed to verify the specific expression of serine protease inhibitor clade E member 1 (SERPINE1). Preliminary study of the role of SERPINE1 in cell invasion was carried out with HTR8-S/Vneo cells. High-quality transcriptomes of 27 607 cells were detected. Three types of trophoblast cells were detected, which were further classified into eight subtypes according to differences in gene expression and Gene Ontology (GO) function. We identified 110 differentially expressed genes (DEGs) in trophoblast cells between the AMA and control groups, and the DEGs were enriched in multiple pathways related to cell invasion. In-vitro transwell assays suggested that the invading trophoblast cells in AMA women were reduced. SERPINE1 was specifically expressed in the trophoblast, and its expression was higher in AMA women (P<0.05). Transfection of human SERPINE1 (hSERPINE1) into HTR8-S/Vneo trophoblast cells showed fewer invading cells in the hSERPINE1 group. Impaired cell invasion may underlie the increased risk of adverse pregnancy outcomes in AMA women. Abnormal expression of SERPINE1 in extravillous trophoblast (EVT) cells appears to play an important role.Keywords：Advanced maternal age (AMA);Pregnancy complications;Placenta;Trophoblast;Cell invasion;Serine protease inhibitor clade E member 1 (SERPINE1)- 203
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Published：2022-09-15
Research Article
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