| 1 | Naturally occurring spike mutations influence the infectivity and immunogenicity of SARS-CoV-2显示文摘Mutations in SARS-CoV-2 variants of concern(VOCs)have enhanced transmissibility and immune evasion with respect to current vaccines and neutralizing antibodies(NAbs).How naturally occurring spike mutations affect the infectivity and antigenicity of VOCs remains to be investigated.The entry efficiency of individual spike mutations was determined in vitro using pseudotyped viruses.BALB/c mice were immunized with 2-dose DNA vaccines encoding B.1.1.7,B.1.351,B.1.1.529 and their single mutations.Cellular and humoral immune responses were then compared to determine the impact of individual mutations on immunogenicity.In the B.1.1.7 lineage,Del69–70 and Del 144 in NTD,A570D and P681H in SD1 and S982A and D1118H in S2 significantly increased viral entry,whereas T716I resulted in a decrease.In the B.1.351 lineage,L18F and Del 242–244 in the NTD,K417N in the RBD and A701V in S2 also increased viral entry.S982A weakened the generation of binding antibodies.All sera showed reduced cross-neutralization activity against B.1.351,B.1.617.2(Delta)and B.1.1.529(Omicron BA.1).S982A,L18F,and Del 242–244 hindered the induction of cross-NAbs,whereas Del 69–70,Del144,R246I,and K417N showed the opposite effects.B.1.351 elicited adequate broad cross-NAbs against both B.1.351 and B.1.617.2.All immunogens tested,however,showed low neutralization against circulating B.1.1.529.In addition,T-cell responses were unlikely affected by mutations tested in the spike.We conclude that individual spike mutations influence viral infectivity and vaccine immunogenicity.Designing VOC-targeted vaccines is likely necessary to overcome immune evasion from current vaccines and neutralizing antibodies. | Qiaoli Peng Runhong Zhou Na Liu Hui Wang Haoran Xu Meiqing Zhao Dawei Yang Ka-Kit Au Haode Huang Li Liu Zhiwei Chen | 2022 | Cellular & Molecular Immunology2022，19，11： | 0 |
| 2 | Changes of biochemical indices in brain, liver tissue and serum in mice with Alzheimer disease after Chinese medicine treatment显示文摘BACKGROUND: Alzheimer disease is a main type of dementia, and the important clinical characteristic is the rapid declines of memory and cognitive ability. OBJECTIVE: To study changes of biochemical indices in brain, liver tissue and serum, as well as memory of mice with Alzheimer disease after Chinese medicine treatment. DESIGN: A comparative animal experimental observation. SETTING: Haierfu Research Center of Youjiang Medical College for Nationalities. MATERIALS: Forty-eight healthy Kunming mice (24 males and 24 females), 3 months old, were provided by the animal room of Youjiang Medical College for Nationalities. The animals were divided into four groups according to sex and body mass: control group, model group, Wuyuan Buxue treated group, Haierfu treated group, and 12 mice in each group. Wuyuan Buxue oral liquid was extracted from Polygonum multiflorum Thunb (red, radix) and longan meat (country medicine quasi- word B20020828). Haierfu oral liquid was extracted from Yinhua, poriacocos, licorice, etc (Q/452600RYYLC01-92). METHODS: The experiment was completed in Haierfu Research Center and Institute of Heavy Metal and Fluorosis-Arsenism of Youjiang Medical College for Nationalities from May 2006 to December 2006. ① All animals except those in the control group were given feed which was mixed with AlCl3 (12 g/L), and they could freely drink 3 g/L Al(NO3)3. The mice in the control group were given normal feed. Wuyuan Buxue oral liquid and Haierfu oral liquid were distilled by distilled water for one time respectively. Five months after model establishment, mice in the Wuyuan Buxue treated group and Haierfu treated group were given intrapastric perfusion of Wuyuan Buxue oral liquid and Haierfu oral liquid respectively, and those in the model group and control group were given intrapastric perfusion of distilled water of the same volume. All the mice were treated for 45 days. ② The swimming time (s) and error times were determined with Y-shape water maze before and after experiment; Hemoglobin was determined by method of HICN. After treatment, serum was isolated from eyeballs to determine the activities of glutathione peroxidase (GSH-PX), urea and cholesterol. The animals were executed to remove brain and liver, then 10% homogenate was prepared to determine the activity of acetylcholinesterase (AChE), clearance of O2–·, content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and GSH-PX. MAIN OUTCOME MEASURES: ① Swimming time and error times in the water maze, and the content of hemoglobin; ② alanine aminotransferase (ALT) activity and contents of urea and cholesterol in serum after treatment; ③ Activities of GSH-PX, AChE and SOD, and MDA content in liver, and AChE activity in brain after treatment. RESULTS: Totally 48 mice were used, and some of them died due to unknown reasons, finally 32 mice (8 in each group) were involved in the analysis of results. ① Content of hemoglobin before and after treatment: There were obvious changes in the groups (P < 0.05). ② Comparison of ALT, cholesterol and urea in serum: The contents of urea in the Wuyuan Buxue treated group and Haierfu treated group were obviously higher than those in the control group and model group (P < 0.05, 0.01); ALT and cholesterol had no significant differences among the groups (P > 0.05). ③ Comparisons of the activities of AChE, GSH-PX and SOD in brain homogenate: The activity of AChE was significantly higher in the control group than the model group and Haierfu treated group, also higher in the Wuyuan Buxue treated group than in the model group (P < 0.05). The activity of GSH-PX in the model group was significantly higher than those in the treated groups (P < 0.01). The activity of SOD in the control group was significantly higher than those in the treated groups (P < 0.05, P < 0.01). ④ Comparison of activities of GSH-PX and SOD, and MDA content in liver homogenate: The activities of GSH-PX and SOD in the model group were obviously lower than those in the Wuyuan Buxue treated group (P < 0.05). MDA content had no obvious differencesamong the groups (P > 0.05). ⑤ Comparison of MDA content, and clearance of O2–· in brain and liver: The MDA content in brain in the model group was significantly higher than those in the treated groups; The clearances of O2–· in liver in the treated groups were significantly higher than those in the control group and model group (P < 0.01). ⑥ Swimming time and error rate in water maze: Before treatment, the swimming speed had no obvious difference among the groups, while the error rate was obviously different. After treatment, there was no obvious difference in the control group; The swimming time was prolonged as compared with that before treatment in the other three groups, and there were no obvious differences among the three group; The error rate was the highest in the model group (25%), and the lowest in the Wuyuan Buxue treated group (8.3%). CONCLUSION: Both the Chinese medicines of Wuyuan Buxue oral liquid and Haierfu oral liquid can improve the biochemical indices in serum, liver and brain, and the memory ability of mice with Alzheimer disease. | Xiangyang Wang Lili Zhang Haode Huang Qiang Qin Guimei Luo Chaogan Li Shuqiu Zhang | 2007 | Neural Regeneration Research2007，2，5： | 0 |
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