ABSTRACT
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.
ABSTRACT
Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
ABSTRACT
[ ABSTRACT] AIM:To establish the insulin resistance rat model for evaluating the correlation of omentin-1 level and insulin resistance.METHODS: SPF male Wistar rats ( n =30 ) were randomly divided into normal control group (NC, n=15) and high-fat diet group (HF, n=15).The rats in NC group were fed with basic diet.The insulin resistant model was established by feeding the rats with high-fat diet in HF group.After 10 weeks, 5 rats in each group were as-sessed by the technique of hyperinsulinaemic-euglycaemic clamp.After the insulin resistant model was successfully estab-lished, the body weight and fasting blood glucose were detected.The concentration of fasting serum omentin-1 was analyzed by ELISA.Fasting serum insulin was measured by radioimmunoassay.RESULTS: No difference of fasting blood glucose between the 2 groups was observed.The level of fasting serum insulin in HF group was significantly higher than that in NC group ( P <0.05 ) .The level of serum omentin-1 in HF group were significantly decreased compared with NC group (P<0.01).Pearson’s correlation analysis showed that negative correlations between serum omentin-1 and fasting serum insulin (r=-0.654,P<0.01), serum omentin-1 and free fatty acid (r=-0.446, P<0.05) was found.CONCLU-SION:In rats, serum omentin-1 level began to decrease at insulin resistance stage.As serum omentin-1 level decreased, the basal insulin level increased, indicating that decreased serum omentin-1 level may be an early factor of IR, diabetes and cardiovascular diseases.
ABSTRACT
By feeding rats with high-fat diet insulin resistant models were induced.Some of the models were treated with intragastric administration of curcumin,then the effects were evaluated by hyperinsulinaemic-euglycaemic clamp technique.Curcumin reduced the level of serum resistin and the expression of resistin mRNA in adipose tissue,and thus ameliorated insulin resistance in rats.