RESUMO
Background: Aggregation, fragmentation, and low yield are issues frequently found during the cell culture process of bispecific antibodies (bsAbs), whose inherent complexity likely plays a role in causing these issues. Methods: In this study, we made a head-to-head comparison between fed-batch cell culture and intensified perfusion cell culture with a symmetric bsAb case. Results: In comparison with the fed-batch culture, a 6.6-fold improvement in integrated viable cell density and a 10.9-fold improvement in volumetric productivity were achieved with the intensified perfusion mode. In addition, a significant decrease in aggregation and fragmentation was observed with the intensified perfusion cell culture. Furthermore, product homogeneity was improved, which was reflected by the increased percentage of capillary isoelectric focusing main group. The quality improvement with intensified perfusion cell culture can be attributed to the shortened product retention in the bioreactor. Conclusions: These findings suggest that intensified perfusion cell culture could be a better choice than traditional fed-batch especially for complex molecules like bsAbs. As this is a single case report, future studies on other cases are needed to further confirm the general applicability of this strategy.
RESUMO
The present study aimed to investigate whether diminazene attenuates myocardial infarction (MI) in rats. In addition, the present study investigated whether ACE2 signaling was involved in the effects of diminazene on protein function. A rat model of acute myocardial infarction (AMI) was established by occlusion of the left anterior descending coronary artery. The AMI model rats received intraperitoneal injections of diminazene (5 mg/kg/day) for 3 days. Treatment with diminazene significantly inhibited the expression of casein kinase and lactate dehydrogenase, and reduced infarct size in AMI rats. The findings indicated that diminazene significantly reduced the levels of inflammatory factors including tumor necrosis factorα and interleukin6, suppressed the protein expression of cytochrome c oxidase subunit 2 (COX2) and inducible nitric oxide synthase (iNOS), and activated angiotensinconverting enzyme 2 (ACE2), angiotensin II receptor type 1 (AT1R) and MAS1 protooncogene, G proteincoupled receptor (MasR) protein expression in AMI model rats. In conclusion, the present study demonstrated that diminazene attenuated AMI in rats via suppression of inflammation, reduction of COX2 and iNOS expression, and activation of the ACE2/AT1R/MasR signaling pathway.
