The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in December 2019. An immediate prevention approach for the outbreak is the development of a vaccination program. Despite a growing number of publications showing the effectiveness of vaccination in preventing SARS-CoV-2 outbreak and reducing the mortality rate, substantial fatal adverse effects were reported after vaccination. Confirmation of the causal relationship of death is required to reimburse under the national vaccination program and could provide a reference for the selection of vaccination. However, a lack of guidelines in the laboratory study and autopsy approach hampered the investigation of post-vaccination death. In this paper, we performed a systematic electronic search on scientific articles related to severe Covid-19 vaccination adverse effects and approaches in identifying the severe side effects using PubMed and Cochrane libraries. A summary on the onset, biochemistry changes and histopathological analyzes of major lethally side effects post-vaccination were discussed. Ultimately, a checklist is suggested to improve the quality of investigation.
A well-documented Achilles heel of current cancer immunotherapy approaches is T cell exhaustion within solid tumor tissues. The pro-inflammatory cytokine interleukin-23 (IL-23) has been utilised to augment chimeric antigen receptor (CAR)-T cells survival and tumor immunity. However, in-depth interrogation of molecular events downstream of IL-23/IL23R signaling is hampered by a paucity of suitable cell models. The current study investigates the differential contribution of IL-2 and IL-23 to the maintenance and differentiation of the IL-23 responsive Kit225 T-cell line. We observed that IL-23 enhanced cellular fitness and survival but was insufficient to drive proliferation. IL-23 rapidly induced phosphorylation of STAT1, 3 and 4, and mRNA expression of IL17A, the archetypal effector cytokine of Th17 cells, but not their lineage markers RORC and NCR1. These observations suggest that IL-23 endowed Th17/ILC3-like effector function but did not promote their differentiation. In contrast, spontaneous differentiation of Kit225 cells towards a Th17/ILC3-like phenotype was induced by prolonged IL-2 withdrawal. This was marked by strongly elevated basal IL17A and IL17F expression and the secretion of IL-17. Together, our data present Kit225 cells as a valuable model for studying the interplay between cytokines and their contribution to T cell survival, proliferation, and differentiation.
A cis-regulatory genetic element which targets gene expression to stem cells, termed stem cell enhancer, serves as a molecular handle for stem cell-specific genetic engineering. Here we show the generation and characterization of a tamoxifen-inducible CreERT2 transgenic (Tg) mouse employing previously identified hematopoietic stem cell (HSC) enhancer for Runx1, eR1 (+24 m). Kinetic analysis of labeled cells after tamoxifen injection and transplantation assays revealed that eR1-driven CreERT2 activity marks dormant adult HSCs which slowly but steadily contribute to unperturbed hematopoiesis. Fetal and child HSCs that are uniformly or intermediately active were also efficiently targeted. Notably, a gene ablation at distinct developmental stages, enabled by this system, resulted in different phenotypes. Similarly, an oncogenic Kras induction at distinct ages caused different spectrums of malignant diseases. These results demonstrate that the eR1-CreERT2 Tg mouse serves as a powerful resource for the analyses of both normal and malignant HSCs at all developmental stages.