Anti-Hematopoiesis related Macrophage monoclonal antibody

Optimizing scaffold architecture for perfect osteointegration depends on good understanding of bone ingrowth in the porous space of implants. This study developed an immunoregulatory agent-based model to discover the osteoinduction mechanism in porous scaffolds. Immunoreaction, macrophage polarization, and the corresponding growth factors were combined in the model, and all played critical roles in recruiting osteogenic cells that migrated into the scaffolds. Angiogenesis was also considered in this model. The bone ingrowth predicted by the model coincides with results from published in vivo experiments. Simulation results suggested that the pore architecture affected the diffusion process of chemotactic factors in the scaffolds, subsequently influencing the complex reactions of diverse cells and the osteoinduction location. In flexural pore spaces, bone formation spread from the periphery into the center of scaffolds due to larger M2 phenotype macrophage populations colonizing boundary regions and the distribution of corresponding growth factors concentration. In straight channels, osteogenic cells migrated further inward and osteoinduction initiated in deeper position as a result of the deeper distribution of osteogenic cytokines concentration field.

Background: The most dangerous atherosclerotic plaques, referred to as "vulnerable," are most likely to trigger acute atherothrombotic events such as myocardial infarction (heart attack) and stroke. Our goal was to uncover the molecular drivers of vulnerable plaque formation. Methods: To elucidate the functional gene modules that drive vulnerable plaque formation, we performed a weighted gene coexpression network analysis integrated with a protein-protein interaction network analysis in human atherosclerotic carotid samples, which identified the candidate gene granulocyte-macrophage colony-stimulating factor 2 (GM-CSF) receptor alpha subunit (CSF2RA). Follow-up in vitro experiments were performed to elucidate the regulatory relationship between CSF2RA and the microRNA miR-532-3p as well as modifiers of macrophagic miR-532-3p-CSF2RA axis expression. Microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) studies elucidated the effect of statins on carotid Huang et al. 1783 miR-532-3p-CSF2RA Axis Regulates Plaques miR-532-3p-CSF2RA axis expression in patients with carotid atherosclerotic disease. Apoe(-/-), LdIr(-/-), and Csf2ra mutant Apoe(-/-) mouse models of atherosclerosis were employed to assess the effects of agomiR-532-3p therapy in vivo. Results: The integrated weighted gene coexpression network analysis/protein-protein interaction network analysis revealed that the macrophagic GM-CSF receptor CSF2RA is significantly upregulated in macrophage-rich vulnerable plaques. Follow-up analysis identified the miR-532-3p-CSF2RA axis, as miR-532-3p downregulates CSF2RA via binding to CSF2RA's 3'UTR. Macrophagic miR-532-3p-CSF2RA dysregulation was enhanced via modified low-density lipoprotein or tumor necrosis factor alpha exposure in vitro. Moreover, this miR-532-3p-CSF2RA dysregulation was observed in human vulnerable plaques and Apoe(-/-) mouse plaques, effects rescued by statin therapy. In vivo, agomiR-532-3p therapy suppressed murine plaque formation and promoted plaque stabilization in a Csf2ra-dependent manner. Conclusion: Macrophagic miR-532-3p-CSF2RA axis dysregulation is a key driver in vulnerable plaque formation.