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Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by overproduction of red blood cells. We have performed a comprehensive characterization of blood immune cells for expression of naïve and memory receptors as well as βm-associated and βm-free MHC class I heavy chains, also known as closed and open conformers, respectively, in PV patients and age-matched controls (CTR). We show that the peripheral CD3CD8 T cell pool in PV patients is clearly divided into two discrete populations, a more granular CD3CD8 T cell population enriched in effector-memory CD45RA T cells (CD8 TEMRA) when compared to CTR (P < 0.001), and a less granular CD3CD8 T cell population that is completely absent in the CTR group (78 vs. 0%, P < 0.001) and is a mixture of naïve (CD8 T) and CD8 TEMRA cells expressing intermediate levels of CD28, i.e., CD3CD8CD28. While the percentage of CD3CD8 TN cells correlated positively with the number of erythrocytes, the percentage of CD3CD8 TEMRA correlated negatively with the number of platelets. Finally, we report that PV patients' lymphocytes and monocytes display lower levels of closed (W6/32) MHC-I conformers at the cell surface while exhibiting increased amounts of open (HC-10) MHC-I conformers. The implications of this distinctive immune signature are discussed.
A novel gliclazide-loaded elastomeric carbohydrate pharmaceutical vehicle was successfully developed. This new siliconized alginate platform showed pseudoplastic rheology with a zeta potential ranging from (−43.8 mV to −75.5 mV). A Buchi-B390 encapsulator was employed to formulate different types of silicone-grafted alginate microcapsules loaded with gliclazide relying on the vibrational ionic gelation technology. The use of tetraethyl orthosilicate (TEOS) to crosslink the silicone elastomer (hydroxy terminated polydimethylsiloxane) of this new platform had improved the gliclazide encapsulation (>92.13% ± 0.76) of the free-flowing composite microcapsules, which showed good mechanical durability (up to 12 h in PBS pH 6.8) and promising results to sustain the drug release.
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