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Hirudin variants are the most powerful thrombin inhibitors discovered to date, with a lower risk of bleeding than heparin. For anticoagulation, the C-termini of hirudin variants bind to the exocite I of thrombin. Anticoagulant effects of gene-recombinant hirudin are weaker than natural hirudin for the reason of lacking tyrosine O-sulfation at C-terminus.An integrative pharmacological study was carried out using molecular dynamic, molecular biological and in vivo and in vitro experiments to elucidate the anticoagulant effects of protein-engineered hirudins.Molecular dynamic analysis showed that modifications of the C-termini of hirudin variant 1 of Hirudo medicinalis (HV1) and hirudin variant 2 of Hirudinaria manillensis (HM2) changed the binding energy of the C-termini to human thrombin. The study indicated that Asp61 of HM2 that corresponds to sulfated Tyr63 of HV1 is critical for inhibiting thrombin activities. Further, the anticoagulant effects of HV1 and HM2 were improved when the amino acid residues adjacent to Asp61 were mutated to Asp. These improvements were prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time of human blood, and decreased K

In tropical and subtropical areas, allergens from the dust mite speciesTo generate a chimeric virus-like particle containing HBcAg, Blo t 5 and Blo t 21 that can treat allergies caused by To produce allergic asthma in mice, prokaryotic expression and purification ofIn allergy-induced mouse model experiments, the fusion allergen rBlo t 5-21 was more effective than the individual allergens rBlo t 5 and rBlo t 21 at inducing allergy. We found that vaccinating allergic mice with the recombinant fusion protein vaccine HBcAg-rBlo t 5-21 alleviated allergy symptoms elicited by the rBlo t 5-21 allergen. Vaccination with HBcAg-rBlo t 5-21 resulted in a decrease in total serum IgE levels, suppression of anaphylaxis, and reduction of inflammatory cell infiltration into lung tissue as compared to the PBS group.HBcAg-rBlo t 5-21, a protein vaccine containing both the hepatitis B core antigen and the

Oxidative stress is one of the causes of aging and other diseases. Nrf2 is the main transcription factor regulating antioxidant gene expression. In recent years, it has been found that inhibiting Nrf2 activity or increasing oxidative pressure can replicate premature aging defects, and reactivating Nrf2 activity can reverse nuclear aging defects and restore cell vitality. SIRT6 is one of the few proteins that can regulate life span and aging at the same time. SIRT6 gene deficient mice show degenerative changes similar to human premature aging 3 weeks after birth and eventually die. SIRT6 deficient cells show the characteristics of accelerated aging, while the deletion of SIRT6 in human cells does not directly lead to the damage of genetic material in the nucleus and genomic instability, but significantly reduces the antioxidant capacity of cells and causes the accumulation of intracellular reactive oxygen species and DNA oxidation products. At present, the interaction between Nrf2 and SIRT6 protein and its mechanism are not clear. In this study, yeast two-hybrid and tag pulldown methods were used to analyze the protein interaction domain between Nrf2 and SIRT6. The experiment found that SIRT6 directly interacts with Nrf2, SIRT6 Interacts with the Neh1 and Neh3 domains of Nrf2.