A Self-Biomineralized Novel Adenovirus Vectored COVID-19 Vaccine for Boosting Immunization of Mice

Virologica Sinica - SARS-CoV-2 has caused more than 3.8 million deaths worldwide, and several types of COVID-19 vaccines are urgently approved for use, including adenovirus vectored vaccines....     

Application of germ-free NOD-scid IL2rgnull mice as a humanized model for tumor microbiome precision medicine

正In 2013, tumor immunotherapy topped the list of the top ten scientific breakthroughs(Couzin-Frankel, 2013), and it was widely used in the treatment of lung cancer, kidney cancer,and melanoma(Routy et al., 2018). However, the response rate of patients to tumor immunotherapy varies, and usually,only a small percentage of patients respond well to treatment(Sambi et al., 2019).     

Congestive heart failure in COX2 deficient rats

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG) formation by targeting cyclooxygenase (COX) 1 and 2.Long-term use of NSAIDs that selectively inhibit COX2 increases the risk for thrombotic events,cardiac failure,and hypertension.However,the underlying mechanisms remain unclear.In this study,COX1- and COX2-deficient rats were created via Cas9/RNA-mediated gene targeting.DNA genotyping and Western blot analysis confirmed successful generation of COX1~(-/-)and COX2~(-/-)rats.Adult COX1~(-/-)rats grew normally,while more than 70%of COX2~(-/-)rats after wean died within 2 months.Echocardiography showed markedly reduced left ventricular ejection fraction and fractional shortening in adult COX2~(-/-)rats compared to those in wildtype (WT) controls.Histological analysis revealed accumulation of inflammatory cells and severe interstitial and perivascular fibrosis in COX2~(-/-)cardiac tissues.Moreover,cardiac ATP and acetyl-Co A production was dramatically decreased in COX2~(-/-)rats.Consistently,the expression of genes related to mitochondrial oxidation,such as those that encode for subunits of pyruvate dehydrogenase complex and acyl Co A dehydrogenases,were downregulated,while glycolytic hexokinase 1 (HK1) was upregulated in COX2~(-/-)heart tissues.These observations indicate that COX2-deficient rats developed spontaneously heart failure,likely as a result of dysregulated cardiac energy metabolism.     

Th2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granulocyte colony-stimulating factor-primed donor T cells

Acute graft-versus-host disease(a GVHD) is caused by allo-activated donor T cells infiltrating target organs. As a regulator of immune function, granulocyte colony-stimulating factor(G-CSF) has been demonstrated to relieve the a GVHD reaction.However, the role of G-CSF-primed donor Tcells in specific target organs is still unknown. In this study, we employed a classical MHC-mismatched transplantation mouse model(C57BL/6 into BALB/c) and found that recipient mice transplanted with GCSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated group. This protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this a GVHD mouse model, especially in the lung and gut. Moreover, we found that Tcells polarized towards Th2 cells and regulatory T cells were increased in specific target organs. In addition, G-CSF treatment inhibited inducible co-stimulator(ICOS) expression and increased the expression of tolerance-related genes in recipient mice. Our study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated a GVHD, especially for its precise regulation in GVHD target organs.