Nine components pharmacokinetic study of rat plasma after oral administration raw and prepared Semen Cassiae in normal and acute liver injury rats.

In China, Semen Cassiae has long been used to protect liver, brighten eyes, and relieve constipation. Prepared Semen Cassiae is produced from raw Semen Cassiae by processing, the two forms of Semen Cassiae have different clinical applications. Pathological state is an important factor affecting the efficacy of drugs, the pharmacokinetic behavior of drugs could be significantly changed when people or animal were under different pathological state. To clarify the effect of processing mechanism and pathological state for pharmacokinetic behavior, the pharmacokinetics of nine components of raw and prepared Semen Cassiae under normal and acute liver injury rats were examined. The results showed that the bimodal phenomenon appeared on the plasma concentration-time profiles of obtusin, emodin, chrysophanol, aloe emodin and rhein. The Tmax of aurantio-obtusin, obtusin, chrysoobtusin, emodin, chrysophanol, aloe emodin, physcion in normal groups administrated prepared Semen Cassiae were shorter than those administrated raw Semen Cassiae. For the AUC0-t , aurantio-obtusin, obtusin, chrysoobtusin, chrysophanol, aloe emodin and physcione in model groups administrated prepared Semen Cassiae were significantly higher than other groups, unlike above components, rhein had poor absorption in model groups. The study would be useful for further studies on pharmacokinetics and clinical application of raw and prepared Semen Cassiae.

Prevalence and factors associated with metabolic syndrome in first hospitalization for major depression disorder patients.

Major depressive disorder (MDD) is a common and socially burdensome psychiatric disorder with a causal and complex relationship with metabolic syndrome (MetS), which is often co-morbid. However, the prevalence and risk factors for MetS in patients with MDD are inconclusive. The purpose of this study is to investigate the prevalence and factors influencing MetS in first hospitalization MDD patients. A total of 981 MDD patients were included. Sociodemographic and general clinical data were collected from the patients, while metabolism-related parameters were also measured, and psychological symptoms were assessed. Our study found that the prevalence of MetS in the study population was 9.68%. MDD patients with MetS had higher levels of metabolism-related parameters and more severe psychological symptoms. We identified risk factors for MetS and its severity separately: age of onset of MDD, more severe depressive symptoms, and higher thyroid stimulating hormone (TSH) levels were risk factors for the development of MetS, whereas higher TSH levels were risk factors for the severity of MetS. Our results suggest that MetS is not highly prevalent in MDD patients, but certain risk factors may increase its likelihood and severity, and that these findings could be beneficial for clinical intervention and care of MetS.

The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P- and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses.