Morphological, cell, and protein characterization of platelet rich fibrin provides a better understanding of the clinical effects and improvement of clinical guidelines for several medical applications. Once well physicochemical and biologically characterized, the use of an injectable platelet rich fibrin can be extended to other applications in the field of orthopedics, periodontics, and implant dentistry on the repairing process of both soft and mineralized tissues.

Background and Purpose: Inflammation associated with the tumour microenvironment (TME) plays a critical role in the cancer development, and immunotherapeutic strategies that aim to modulate the immune response in cancer have been crucial. In this study, a Methotrexate-loaded (MTX) poly(lactic-co-glycolic acid)-based (PLGA) drug nanocarrier covered with polyethyleneimine (Pei) and hyaluronic acid (HA) was developed and combined with anti-PD-L1 immune checkpoint inhibitor to investigate the anti-cancer and immunomodulatory performance in the breast cancer TME. Experimental Approach: From the allographic model of orthotopic tumour growth, the tumours were evaluated by qRT-PCR and immunohistochemistry. Complementary analysis of cell death profile, cell migration and macrophage polarization were evaluated in vitro. Key Results: Naked or HA-coated PeiPLGA-MTX nanoparticles (NPs) used alone or combined with anti-PD-L1 promoted tumorigenic course modification as well as TME immunomodulation with significant reduction of primary tumour and metastasis. For the first time, we reported the involvement of M2 macrophages as major orchestrator of this response via NPs-mediated IL-10/STAT3/NF-κB downregulation. The suppression of this signalling axis seems to have disrupted the crosstalk between immune and malignant cells, reducing critical pro-tumour events such as: immune escape; cell survival; drug and apoptosis resistance, as well as some key mechanisms in the epithelial-mesenchymal transition. Conclusion and Implications: These results contribute to our understanding of the immunological mechanisms that underlie the anti-tumorigenic effects of an effective This article is protected by copyright. All rights reserved. and promising drug nanocarrier capable of satisfactorily immunomodulating the TME and providing a favourable outcome in breast cancer.

The structural characterization and the anticoagulant potential of a novel heparin/heparan sulfate-like compound from the heads of Litopenaeus vannamei shrimp are described. While it is distinct from either heparin or heparan sulfate, enzymatic depolymerization and nuclear magnetic resonance spectroscopy analyses revealed that this molecule does share some structural features with heparin, such as the high degree of N- and 6-O-sulfation and minor N-acetylation, and with heparan sulfate, in the glucuronic acid content. Its ability to stabilize human antithrombin explains its significant anticoagulant activity in aPTT and Factor-Xa inhibition assays. Interestingly, in contrast to mammalian heparin, the shrimp compound displayed negligible hemorrhagic effect. Together, these findings have particular interest since they reveal a novel molecule with significant anti-Xa activity coupled with low bleeding effects which make the shrimp heparin/HS-like compound a potential alternative for mammalian heparin.

The occurrence of a natural and unmodified highly sulfated chondroitin sulfate from Litopenaeus vannamei heads (sCS) is herein reported. Its partial digestion by Chondroitinases AC and ABC together with its electrophoretic migration profile revealed it as a highly sulfated chondroitin sulfate despite its average molecular weight being similar to CSA. Using orthogonal 1D/2D NMR experiments, the anomeric signals (δ 4.62/106.0) corresponding to unusual 2,3-di-O-Sulfo-GlcA (∼36%), U3 (δ 4.42/84.1, ∼63%) and U2 (4.12/80.1, ∼50%) substitutions were confirmed. In addition, non-sulfated GlcA (δ 4.5/106.3) linked to 4-O- (A1, 36%) or 6-O-Sulfo (A1, 28%) GalNAc (δ 4.64/103.5) was observed. Although the biological role of sCS in shrimp is unknown, its influence on hemostasis was also demonstrated. The sCS identification brings to light new questions about the hierarchical model of GAGs biosynthesis and contributes to the better understanding of the subtle relationship between GAGs structure and function.