Objective: The IL-33/ST2 pathway plays a fundamental role in the cardiovascular system and can be considered as a new therapeutic strategy for the treatment or prevention of cardiovascular diseases. ST2, as an interleukin (IL)-1 receptor family member, has transmembrane (ST2L) and soluble (sST2) isoforms. sST2 neutralizes IL-33 and thereby inhibits the cardioprotective role of IL-33/ST2L signaling pathway. Increase in sST2 level is associated with weak cardiac output and can be a predictor of mortality in heart failure (HF). Thereby, we hypothesized that there may be a relationship between the cardioprotective effects of carvedilol and sST2 and IL-3 in HF patients. Methods: sST2 and IL-33 were measured in serum of 66 individuals; 22 healthy volunteers and 44 suffering from HF; among whom 25 patients received carvedilol and the other 19 patients did not receive any β-blockers. Results: Lack of association between serum levels of IL-33 and sST2 was observed between HF patients and healthy individuals (2.4466 ± 0.69 vs 2.6748 ± 0.33 and 3416.6 ± 1089.1 vs 2971.6 ± 792.5, respectively). Our results indicated no significant difference between sST2 and IL-33 levels in HF patients who did not receive beta-blockers and patients receiving carvedilol (P=0.59 and P=0.97). Conclusion: Our results showed a lack of association between serum levels of IL-33 and sST2 and HF. Moreover, the results do not confirm the cardioprotective mechanism of carvedilol by means of IL-33/sST2 pathway.
Currently, many efforts have been made against Coronavirus 2019 (COVID-19) as a global outbreak. So far, several vaccines with different platforms are available in the market. Various variants of the SAR-CoV-2 virus have evolved over time. The emergence of variant of Concerns (VOCs), especially new subvariants of BA.4 and BA.5, which can neutralize the effect of current vaccines. Therefore, in this study, we used the bioinformatics approach to design an effective novel candidate vaccine against Variant of Concern (VOC) of COVID-19 (B.1.1.529 or Omicron) based on Spike (S1_ receptor-binding domain or RBD) protein sequence. Here, we employed bioinformatics tools to design a novel fusion protein construct containing the mutant sequence of Omicron Spike_S1_RBD region (as target antigen) and amino acid sequence of human β-defensin-2 as adjuvant molecule. Then, the mutant RBD and β-defensin-2 amino acid sequences were joined together by the suitable linker and novel vaccine construct was designed. Subsequently, immunological and structural evaluations such as antigenicity, allergenicity, physicochemical properties, 3D modeling, molecular docking, and fast flexibility simulations, immune responses simulation as well as in silico cloning were performed. Immunological and structural computational data showed that designed vaccine construct potentially has proper capacity for inducing immune responses against BA.4/5 subvariant of Omicron. Based on the preliminary results, in vitro and in vivo experiments are required for validation in the future.
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