Background: The primo vascular system can be viewed as a circulatory system that plays a therapeutic function in regenerating the body tissue. The anti-CD3 monoclonal antibody was used as an immunotherapeutic agent to treat the novel coronavirus infection . Objectives: In this study, we observed the effect of injecting lymph nodes with Foralumab, an anti-human CD3 epsilon therapeutic monoclonal antibody, on primo vessels. Methods: The structure and atomic stoichiometry of the antibody were determined by transmission electron microscopy and energy dispersive spectroscopy. Alcian blue dying solution was injected into the lymph nodes of the abdominal vena cava of rabbits, and the solution further flowed into the lymph vessels. Results: A primo vessel with primo nodes stained with Alcian blue was clearly visible in the lymph vessel. By injecting Foralumab into lymph nodes of rabbits with lipopolysaccharide-induced inflammation, the floating primo vessel in the lymph vessel appeared thicker and was distinctly visible.
Conclusion:The observation of the primo vessel post-treated with Foralumab in the inflamed lymphatic system suggests the possibility of a functional role of the primo vascular circulatory system in pathophysiological conditions.
Cytokine storm is characterized by increased levels of proinflammatory cytokines. Magnetic nanoparticles (MNPs)-conjugated antibody therapy is promising in treating cytokine storms. This study will evaluate the time-dependent distribution of the silica-coated MNP (MNP-Si) in the spleen and consequent serum cytokine changes for 30 days. MNP-Si were administered to female BALB/c mice via the tail vein injection. The distribution of Fe in the spleen tissue was analyzed by ICP-MS both in control and MNP-Si-treated mice. Moreover, the acute immune toxicity in serum was investigated by analyzing IFN-γ and IL-6 levels. Fe in the control spleen is 0.98 × 106 μg/mg of dry weight. The highest average concentration of Fe in the spleen was measured on day 10 (1.4 × 106 μg/mg). And at day 30, Fe levels decreased to 1.0 × 106 μg/mg. IFN-γ levels significantly increase to a maximum on day 6 and remain elevated until day 30. IL-6 levels are not elevated after MNP-Si administration. Although the cytokines in tissue homogenates were elevated at day 20, the data are statistically non-significant. In conclusion, the proinflammatory cytokine IFN-γ levels were increased on day 6, indicating induced activation of macrophages and systemic inflammation after MNP-Si administration. Therefore, the dose and composition of the MNP-Si should be revised for potential usage for therapeutic purposes.
Given the importance of cyclin-dependent kinases (CDKs) in the maintenance of cell development, gene transcription, and other essential biological operations, CDK blockers have been generated to manage a variety of disorders resulting from CDK irregularities. Furthermore, CDK9 has a crucial role in transcription by regulating short-lived anti-apoptotic genes necessary for cancer cell persistence. Addressing CDK9 with blockers has consequently emerged as a promising treatment for cancer. This study scrutinizes the effectiveness of nature-derived compounds (geniposidic acid, quercetin, geniposide, curcumin, and withanolide C) against CDK9 through computational approaches. A molecular docking study was performed after preparing the protein and the ligands. The selected blockers of the CDK9 exerted reliable binding affinities (−8.114 kcal/mol to −13.908 kcal/mol) against the selected protein, resulting in promising candidates compared to the co-crystallized ligand (LCI). The binding affinity of geniposidic acid (−13.908 kcal/mol) to CDK9 is higher than quercetin (−10.775 kcal/mol), geniposide (−9.969 kcal/mol), curcumin (−9.898 kcal/mol), withanolide C (−8.114 kcal/mol), and the co-crystallized ligand LCI (−11.425 kcal/mol). Therefore, geniposidic acid is a promising inhibitor of CDK9. Moreover, the molecular dynamics studies assessed the structure–function relationships and protein–ligand interactions. The network pharmacology study for the selected ligands demonstrated the auspicious compound–target–pathway signaling pathways vital in developing tumor, tumor cell growth, differentiation, and promoting tumor cell progression. Moreover, this study concluded by analyzing the computational approaches the natural-derived compounds that have potential interacting activities against CDK9 and, therefore, can be considered promising candidates for CKD9-induced cancer. To substantiate this study’s outcomes, in vivo research is recommended.
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