1.Role of Caveolin-3/ERK signaling pathway in reduction of myocardial ischemia-reperfusion injury by morphine preconditioning in rats with chronic heart failure: an in vitro experiment
Chengxiao GUO ; Shiyun JIN ; Xudong HU ; Zhaofei LUO ; Shufang HE ; Ye ZHANG
Chinese Journal of Anesthesiology 2022;42(2):161-165
Objective:To investigate the role of Caveolin (Cav-3)/extracellular signal-regulated kinase (ERK) signaling pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by morphine preconditioning in rats with chronic heart failure.Methods:Clean-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, were used in this study.Chronic heart failure was induced by ligating the left anterior descending coronary artery for 6 weeks.Thirty-six Langendorff-perfused hearts with chronic heart failure were divided into 4 groups ( n=9 each) by a random number table method: myocardial I/R group (group IR), morphine preconditioning group (group MP), morphine preconditioning plus methyl-β-cyclodextrin group (group MP+ MβCD), and methyl-β-cyclodextrin group (group MβCD). Global myocardial I/R was induced by 30 min ischemia followed by 120 min reperfusion.In group MP, after 15 min of equilibration, hearts were subjected to 3 cycles of 5 min perfusion with K-H solution containing 1 μmol/L morphine for preconditioning followed by 5 min perfusion with K-H solution, 30 min in total, and after the end of treatment, hearts were subjected to 30 min ischemia followed by 120 min reperfusion.In group MP+ MβCD, hearts were perfused with K-H solution containing 200 μmol/L methyl-β-cyclodextrin at 10 min before preconditioning with morphine, and the other treatments were similar to those previously described in group MP.In group MβCD, hearts were perfused with K-H solution containing 200 μmol/L methyl-β-cyclodextrin at 40 min before ischemia, and the other treatments were similar to those previously described in group IR.At the end of 15 min of equilibration (T 0) and 5 and 10 min of reperfusion (T 1, 2), coronary outflow was collected for determination of actate dehydrogenase (LDH) activity by chemical colorimetry.Myocardial infarct size (IS) and area at risk (AAR) were measured, and IS/AAR was calculated at the end of 120 min reperfusion.Myocardial tissues of left ventricle were taken to detect the expression of Cav-3, ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) by Western blot, and p-ERK1/2/ERK1/2 ratio was calculated. Results:Compared with group IR, IS, IS/AAR and LDH activity in coronary outflow were significantly decreased, the expression of Cav-3 was up-regulated, and p-ERK1/2/ERK1/2 ratio was increased in group MP ( P<0.05). Compared with group MP, IS, IS/AAR and LDH activity in coronary outflow were significantly increased, the expression of Cav-3 was down-regulated, and p-ERK1/2/ERK1/2 ratio was decreased in group MP+ MβCD ( P<0.05). Conclusions:The mechanism by which morphine preconditioning reduces I/R injury may be related to activation of Cav-3/ERK signaling pathway in rats with chronic heart failure.
2.Effects of subchronic exposure to benzoɑpyrene on memory function and mRNA expressions of NMDA receptors in different brain regions in rats
Zhaofei LI ; Shanshan CHANG ; Cancan GUO ; Yi LYU ; Jinping ZHENG
Journal of Environmental and Occupational Medicine 2022;39(7):804-808
Background The altered expressions of hippocampal N-methyl-D-aspartate (NMDA) receptors induced by benzo[ɑ]pyrene (BaP) causes short-term spatial learning and memory impairment in humans and animals, but whether BaP causes alterations of NMDA receptor subunits in other brain regions and the associated neurotoxic mechanism is still essentially unknown. Objective To observe the mRNA expressions of NR1, NR2A, and NR2B of NMDA receptor subunits in different brain regions in SD rat model with subchronic exposure to BaP, and to provide a basis for in-depth study of the mechanism of BaP-induced neurotoxicity. Methods Forty male SD rats were selected and randomly divided into a control group and 1.00, 2.50, and 6.25 mg·kg−1 BaP exposure groups with 10 rats in each group. The exposure rats received intraperitoneal injection of BaP every other day for 90 d.The average latency to platform, the average total distance, and the duration spent in previous quadrant were measured by the Morris Water Maze. Real-time fluorescence quantitative PCR was used to detect the mRNA expressions of NR1, NR2A, and NR2B in hippocampus, cortex, cerebellum, and striatum of rats. Results The average latency to platform and the average total distance in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly prolonged compared with the control group (P<0.05), and the duration that rats spent in previous quadrant in the 6.25 mg·kg−1 BaP group was significantly shortened (P<0.05). Compared with the control group, the mRNA expressions of NR1 and NR2B in the hippocampus in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly reduced (P<0.05), and the NR2A mRNA expression in the hippocampus in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); the mRNA expressions of NR1 and NR2B in the cortical tissue in the 6.25 mg·kg−1 BaP group were significantly reduced (P<0.05), and the mRNA expression of NR2A in the cortical tissue in the 1.00 mg·kg−1 BaP group was reduced; the mRNA expression of NR2B in the cerebellar tissue in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); there were no differences in the mRNA expressions of NMDA receptor subunits in the striatum tissue (P>0.05). Conclusion Subchronic BaP exposure can cause short-term spatial learning and memory impairment in rats, which may be related to the down-regulation of mRNA expressions of NR1, NR2A, and NR2B in hippocampus, changes of mRNA expressions of NR1, NR2A, and NR2B in cortical area, and the down-regulation of NR2B mRNA expression in cerebellum.
3. Investigation and analysis on characteristics of a cluster of COVID-19 associated with exposure in a department store in Tianjin
Weishen WU ; Yonggang LI ; Zhaofei WEI ; Penghui ZHOU ; Likun LYU ; Guoping ZHANG ; Ying ZHAO ; Haiyan HE ; Xiaoyan LI ; Lu GAO ; Xiumei ZHANG ; Hui LIU ; Ning ZHOU ; Yan GUO ; Xiaomeng ZHANG ; Dan ZHANG ; Jing LIU ; Ying ZHANG
Chinese Journal of Epidemiology 2020;41(4):489-493
Objective:
To describe the epidemiological characteristics of a cluster of COVID-19 cases reported in Baodi district of Tianjin as of 18 February, 2020, which might be associated with the exposure in a local department store, and provide suggestions for prevention and control strategy development.
Methods:
The basic characteristics, time and area distributions, clinical manifestations, epidemiological history and transmission mode of the COVID-19 cases associated with the department store exposure were analyzed.
Results:
A total of 40 COVID-19 cases were associated with the department store exposure, accounting for 75.47% of the total confirmed cases (53 cases) reported in Baodi district. The cases were mainly at the age of 60 years or older (35.00%) and farmers (40.00%). The main clinical manifestations included fever (95.00%), cough (35.00%), and diarrhea (15.00%). The proportion of confirmed severe cases was 32.50%. The incidence curve showed that the incidence peak occurred on 31 January, 2020. Among the 40 cases, 6(15.00%) were department store employees, 19(47.50%) were customers and 15(37.50%) were close contacts (secondary cases). The first case occurred on 21 January, 2020, this case was a department store employee who had a purchasing history at whole sale markets in other provinces and cities before the onset, and 3 employees were still on duty after symptom onsets. The median of the incubation period of customer cases was 6 days, and the median of the interval between onset and medical treatment of customer cases was 7 days.
Conclusion
This was a cluster epidemic of COVID-19, which might be associated with the exposure in the department store. By now, the current prevention and control measures have achieved satisfied effects.
4.Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity.
Fuhua WU ; Shuang LUO ; Yongshun ZHANG ; Yangsen OU ; Hairui WANG ; Zhaofei GUO ; Chunting HE ; Shuting BAI ; Penghui HE ; Min JIANG ; Xiaoyan CHEN ; Guangsheng DU ; Xun SUN
Acta Pharmaceutica Sinica B 2023;13(5):2219-2233
Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.