Pro- and Antifibrotic Factors in the Serum of Patients with Chronic Myeloproliferative Disorders

Background. The study of pro- and antifibrotic factors in the serum of patients with Ph-negative chronic myeloproliferative disorders (CMPDs) will allow to understand better the mechanisms of myelofibrosis development, as well as to identify new diagnostic markers. Aim. To assess the correlation between the levels of classic (TGF-β, bFGF, MMP-2, -9, -13 and VEGF) and new proinflammatory serum factors (galectin-3), involved into development of myelofibrosis in different Ph-negative forms of CMPDs and genetic abnormalities. Materials & Methods. The research included 55 CMPD patients (13 with polycythemia vera, 17 with essential thrombocythemia, 25 with primary myelofibrosis) and 8 healthy controls. Whole blood genomic DNA extraction was used to evaluate mutations JAK2V617F, CALR (deletions and insertions), MPLW515L, and MPLW515K. Antibody-immobilized ELISA was used to evaluate the levels of galectin-3, TGF-β, bFGF, VEGF, MMP-2, MMP-9 and MMP-13. Results. The analysis showed the differences in serum MMP-9, VEGF, TGF-β and galectin-3 levels in patients with different CMPDs. A tendency towards the decrease of serum MMP-9 levels in patients with CALR mutations was shown. Conclusion. The shown differences between patients with different CMPDs may serve as a basis for improving diagnostic protocols in challenging differential diagnosis of CMPDs

Platelet-mimetic strategies for modulating the wound environment and inflammatory responses

Platelets closely interface with the immune system to fight pathogens, target wound sites, and regulate tissue repair. Natural platelet levels within the body can be depleted for a variety of reasons, including excessive bleeding following traumatic injury, or diseases such as cancer and bacterial or viral infections. Platelet transfusions are commonly used to improve platelet count and hemostatic function in these cases, but transfusions can be complicated by the contamination risks and short storage life of donated platelets. Lyophilized platelets that can be freeze-dried and stored for longer periods of time and synthetic platelet-mimetic technologies that can enhance or replace the functions of natural platelets, while minimizing adverse immune responses have been explored as alternatives to transfusion. Synthetic platelets typically comprise nanoparticles surface-decorated with peptides or ligands to recreate specific biological characteristics of platelets, including targeting of wound and disease sites and facilitating platelet aggregation. Recent efforts in synthetic platelet design have additionally focused on matching platelet shape and mechanics to recreate the marginalization and clot contraction capabilities of natural platelets. The ability to specifically tune the properties of synthetic platelet-mimetic materials has shown utility in a variety of applications including hemostasis, drug delivery, and targeted delivery of cancer therapeutics