Ferritin-binding and ubiquitination-modified mRNA vaccines induce potent immune responses and protective efficacy against SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) incessantly engenders mutating strains via immune escape mechanisms, substantially escalating the risk of severe acute respiratory syndrome. In this context, the urgent development of innovative and efficacious mRNA vaccines is imperative. In our study, we synthesized six unique mRNA vaccine formulations: the Receptor Binding Domain (RBD) monomer vaccine, RBD dimer (2RBD) vaccine, RBD-Ferritin (RBD-Fe) vaccine, ubiquitin-modified wild-type Nucleocapsid gene (WT-N) vaccine, rearranged Nucleocapsid gene (Re-N) vaccine, and an epitope-based (COVID-19 epitope) vaccine, all encapsulated within the lipid nanoparticle SM102. Immunization studies conducted on C57BL/6 mice with these vaccines revealed that the RBD monomer, RBD dimer (2RBD), and RBD-Fe vaccines elicited robust titers of specific antibodies, including neutralizing antibodies. In contrast, the wild-type N gene (WT-N), rearrange N gene (Re-N), and COVID-19 epitope vaccines predominantly induced potent cellular immune responses. Protective efficacy assays in golden hamsters demonstrated that vaccinated cohorts showed significant reduction in lung pathology, markedly lower viral loads in the lungs, nasal turbinates, and trachea, and substantially reduced transcriptional and expression levels of pro-inflammatory cytokines. Overall, our vaccine candidates pave the way for novel strategies in vaccine development against various infectious agents and establish a critical foundation for the formulation of advanced vaccines targeting emerging pathogens.

Pinellia ternata lectin exerts a pro-inflammatory effect on macrophages by inducing the release of pro-inflammatory cytokines, the activation of the nuclear factor-κB signaling pathway and the overproduction of reactive oxygen species.

Pinellia ternata (PT) is a widely used traditional Chinese medicine. The raw material has a throat-irritating toxicity that is associated with the PT lectin (PTL). PTL is a monocot lectin isolated from the tubers of PT, which exhibits mouse peritoneal acute inflammatory effects in vivo. The present study aimed to investigate the pro-inflammatory effect of PTL on macrophages. PTL (50 µg/ml)­stimulated macrophages enhanced the chemotactic activity of neutrophils. PTL (50, 100, 200 and 400 µg/ml) significantly elevated the production of cytokines [tumor necrosis factor­α (TNF-α) , interleukin (IL)­1ß and IL­6]. PTL (25, 50 and 100 µg/ml) induced intracellular reactive oxygen species (ROS) overproduction. PTL also caused transfer of p65 from the macrophage cytoplasm to the nucleus and activated the nuclear factor­κB (NF­κB) signaling pathway. Scanning electron microscope images revealed severe cell swelling and membrane integrity defection of macrophages following PTL (100 µg/ml) stimulation, which was also associated with inflammation. PTL had pro­inflammatory activity, involving induced neutrophil migration, cytokine release, ROS overproduction and the activation of the NF-κB signaling pathway, which was associated with the activation of macrophages.

A new casbane diterpene from Euphorbia pekinensis.

A new casbane diterpenoid, referred to as pekinenin G, together with one cembrane diterpene and four known casbane diterpenoids were isolated from the roots of Euphorbia pekinensis. Their structures were elucidated on the basis of spectroscopic studies and comparison with related known compounds. The six compounds showed different cytotoxic activities against four human cancer cell lines.

Tracing novel hemostatic compounds from heating products of total flavonoids in Flos Sophorae by spectrum-effect relationships and column chromatography.

Flos Sophorae and its processed product have been clinically used to treat hemorrhage. In this study, the total ion chromatographic fingerprints of the heating products of total flavonoids in Flos Sophorae were established by high-performance liquid chromatography with tandem mass spectrometry and the hemostatic activities were studied by hemostatic screening tests in vivo. The spectrum-effect relationships between fingerprints and hemostatic activities were investigated using canonical correlation analysis to trace the peaks responsible for the hemostatic effects. The predicted active peaks in fingerprints were isolated by column chromatography and their structures were identified by NMR spectroscopy and mass spectrometry. The hemostatic activities of them were verified by platelet aggregation and procoagulation assays in vitro. Canonical correlation analysis results showed that peak 8 and peak 11 were correlated most closely, thus probably being the main hemostatic compounds. Through column chromatography separation, peak 8 (compound I) and peak 11 (compound II) were obtained with purities of 95.61 and 93.38%, respectively, and were discovered new hemostatic compounds named as huaicarbon A (I) and huaicarbon B (II), respectively. This study provides a universal model to trace the active compounds of other herbs which have bioactivity enhancement after processing by spectrum-effect relationships and column chromatography.