RESUMO
Mucosal vaccinations for respiratory pathogens provide superior protection as they stimulate localized cellular and humoral immunity at the site of infection. Currently, the major limitation of the intranasal vaccination is using effective adjuvants capable of withstanding the harsh environment imposed by the mucosa. Herein, we describe the efficacy of using a novel biopolymer, N-dihydrogalactochitosan (GC), as a nasal mucosal vaccine adjuvant against respiratory infections. Specifically, using COVID as an example, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV), an MF-59 equivalent. In contrast to AV, intranasal application of GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. Moreover, GC+S+NC vaccinated animals were largely resistant to lethal SARS-CoV-2 challenge and experienced drastically reduced morbidity and mortality, with the animal weights and behavior returning to normal 22 days post infection. In contrast, animals intranasally vaccinated by AV+S+NC experienced severe weight loss, mortality, and respiratory distress, with none surviving beyond 6 days post infection. Our findings demonstrate that GC can serve as a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses.
RESUMO
AIM: To study the inhibitory effect of Xihuang Pill on H
RESUMO
OBJECTIVE To evaluate the qualit y of Xihuang pills ，and to screen the differential markers affecting its quality . METHODS Using muskone as internal reference ，the content of α-pinene and other 4 components were determined by quantitative analysis of multi -components by single marker （QAMS），and compared with the results of external standard method . The fingerprints of 13 batches of Xihuang pills were established by gas chromatography （GC）method. Cluster analysis （CA）and orthogonal partial least squares discriminant analysis （OPLS-DA） were performed by SPSS 25.0 software and SIMCA 14.1 software. The variable importance projection （VIP）value greater than 1 was used as the standard to screen differential markers affecting the quality of the samples . RESULTS The contents of α-pinene，octyl acetate and β-elemene measured by QAMS were 0- 0.628 4，0.378 0-2.679 4 and 0.320 9-0.815 4 mg/g，respectively. The contents of α-pinene，octyl acetate ，β-elemene and musk ketone measured by external standard method were 0.001 5-0.627 1，0.378 0-2.594 7，0.329 2-0.837 0 and 0.385 7-0.806 0 mg/g， respectively. The relative error of the content determination results of the two methods was less than 4%. There were 26 common peaks in 13 batches of Xihuang pills ，and 3 common peaks ，such as octyl acetate ，β-elemene and musk ketone ，were identified ； their similarities were 0.912-0.946. 13 batches of samples could be divided into two categories （S1-S2，S6-S10，S13 were clustered into one category and S 3-S5，S11-S12 were clustered into one category ）. VIP values of peak 7，11，10，17 and 16 were all greater than 1. CONCLUSIONS The content of 4 components such as α-pinene in Xihuang pills combined with GC fingerprint and chemical pattern recognition analysis can be used to evaluate the quality of Xihuang pills . The components corresponding to 5 common peaks such as peak 7 may be differential markers affecting the quality of the samples .
RESUMO
Microglial activation occurs in divergent neuropathological conditions. Such microglial event has the key involvement in the progression of CNS diseases. However, the transcriptional mechanism governing microglial activation remains poorly understood. Here, we investigate the microglial response to traumatic injury-induced neurodegeneration by the 3D fluorescence imaging technique. We show that transcription factors IRF8 and PU.1 are both indispensible for microglial activation, as their specific post-developmental deletion in microglia abolishes the process. Mechanistically, we reveal that IRF8 and PU.1 directly target the gene transcription of each other in a positive feedback to sustain their highly enhanced expression during microglial activation. Moreover, IRF8 and PU.1 dictate the microglial response by cooperatively acting through the composite IRF-ETS motifs that are specifically enriched on microglial activation-related genes. This action of cooperative transcription can be further verified biochemically by the synergetic binding of IRF8 and PU.1 proteins to the composite-motif DNA. Our study has therefore elucidated the central transcriptional mechanism of microglial activation in response to neurodegenerative condition.
