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  • 1
    Online Resource
    Online Resource
    The Double-Edged Sword of Erythrocytes in Health and Disease via Their Adhesiveness
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 12 ( 2023-06-20), p. 10382-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 12 ( 2023-06-20), p. 10382-
    Abstract: Their widespread presence throughout the vasculature, coupled with their reactivity, and thereby to their potential to release reactive oxidative species, or to utilize their anti-oxidative capacities, has promoted much discussion of the role(s) of red blood cells (RBCs) in the progression of health or, alternatively, a wide range of disease states. Moreover, these role(s) have been linked to the development of adhesiveness and, in fact, thereby to the essential pathway to their eventual clearance, e.g., by macrophages in the spleen. These disparate roles coupled with the mechanisms involved are reviewed and given. Following an analysis, novel perspectives are provided; these perspectives can lead to novel assays for identifying the potential for RBC adhesiveness as suggested herein. We describe this paradigm, that involves RBC adhesiveness, hemolysis, and ghost formation, with examples including, inter alia, the progression of atherosclerosis and the suppression of tumor growth along with other disease states.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241210382
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Functional and Mass Spectrometric Evaluation of an Anti-Tick Antigen Based on the P0 Peptide Conjugated to Bm86 Protein
    MDPI AG ; 2020
    In:  Pathogens Vol. 9, No. 6 ( 2020-06-25), p. 513-
    Details
    In: Pathogens, MDPI AG, Vol. 9, No. 6 ( 2020-06-25), p. 513-
    Abstract: A synthetic 20 amino acid peptide of the ribosomal protein P0 from ticks, when conjugated to keyhole limpet hemocyanin from Megathura crenulata and used as an immunogen against Rhipicephalus microplus and Rhipicephalus sanguineus s.l. species, has shown efficacies of around 90%. There is also experimental evidence of a high efficacy of this conjugate against Amblyomma mixtum and Ixodes ricinus species, which suggest that this antigen could be a good broad-spectrum anti-tick vaccine candidate. In this study, the P0 peptide (pP0) was chemically conjugated to Bm86 as a carrier protein. SDS-PAGE analysis of this conjugate demonstrated that it is highly heterogeneous in size, carrying from 1 to 18 molecules of pP0 per molecule of Bm86. Forty-nine out of the 54 lysine residues and the N-terminal end of Bm86 were found partially linked to pP0 by using LC-MS/MS analysis and the combination of four different softwares. Several post-translational modifications of Bm86 protein were also identified by mass spectrometry. High immunogenicity and efficacy were achieved when dogs and cattle were vaccinated with the pP0–Bm86 conjugate and challenged with R. sanguineus s.l. and R. microplus, respectively. These results encourage the development of this antigen with promising possibilities as an anti-tick vaccine.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    URL: Article
    DOI: 10.3390/pathogens9060513
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2695572-6
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  • 3
    Online Resource
    Online Resource
    Replacing the Transfusion of 1–2 Units of Blood with Plasma Expanders that Increase Oxygen Delivery Capacity: Evidence from Experimental Studies
    MDPI AG ; 2014
    In:  Journal of Functional Biomaterials Vol. 5, No. 4 ( 2014-10-27), p. 232-245
    Details
    In: Journal of Functional Biomaterials, MDPI AG, Vol. 5, No. 4 ( 2014-10-27), p. 232-245
    Type of Medium: Online Resource
    ISSN: 2079-4983
    URL: Article
    DOI: 10.3390/jfb5040232
    Language: English
    Publisher: MDPI AG
    Publication Date: 2014
    detail.hit.zdb_id: 2648525-4
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  • 4
    Online Resource
    Online Resource
    Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents
    MDPI AG ; 2016
    In:  Biomolecules Vol. 6, No. 3 ( 2016-07-04), p. 32-
    Details
    In: Biomolecules, MDPI AG, Vol. 6, No. 3 ( 2016-07-04), p. 32-
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom6030032
    Language: English
    Publisher: MDPI AG
    Publication Date: 2016
    detail.hit.zdb_id: 2701262-1
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  • 5
    Online Resource
    Online Resource
    RRx-001 Increases Erythrocyte Preferential Adhesion to the Tumor Vasculature
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 9 ( 2021-04-29), p. 4713-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 9 ( 2021-04-29), p. 4713-
    Abstract: Red blood cells (RBCs) serve a variety of functions beyond mere oxygen transport both in health and pathology. Notably, RRx-001, a minimally toxic pleiotropic anticancer agent with macrophage activating and vascular normalization properties currently in Phase III trials, induces modification to RBCs which could promote vascular adhesion similar to sickle cells. This study assessed whether RBCs exposed to RRx-001 adhere to the tumor microvasculature and whether this adhesion alters tumor viability. We next investigated the biomechanics of RBC adhesion in the context of local inflammatory cytokines after treatment with RRx-001 as a potential mechanism for preferential tumor aggregation. Human HEP-G2 and HT-29 tumor cells were subcutaneously implanted into nu/nu mice and were infused with RRx-001-treated and Technetium-99m (99mTc)-labeled blood. RBC adhesion was quantified in an in vitro human umbilical vein endothelial cell (HUVEC) assay under both normoxic and hypoxic conditions with administration of either lipopolysaccharide (LPS) or Tumor necrosis alpha (TNFα) to mimic the known inflammation in the tumor microenvironment. One hour following administration of 99mTc labeled RBCs treated with 10 mg/kg RRx-001, we observed an approximate 2.0-fold and 1.5-fold increase in 99mTc-labeled RBCs compared to vehicle control in HEPG2 and HT-29 tumor models, respectively. Furthermore, we observed an approximate 40% and 36% decrease in HEP-G2 and HT-29 tumor weight, respectively, following treatment with RRx-001. To quantify RBC adhesive potential, we determined τ50, or the shear stress required for 50% disassociation of RBCs from HUVECs. After administration of TNF-α under normoxia, τ50 was determined to be 4.5 dynes/cm2 (95% CI: 4.3–4.7 dynes/cm2) for RBCs treated with 10 μM RRx-001, which was significantly different (p 〈 0.05) from τ50 in the absence of treatment. Under hypoxic conditions, the difference of τ50 with (4.8 dynes/cm2; 95% CI: 4.6–5.1 dynes/cm2) and without (2.6 dynes/cm2; 95% CI: 2.4–2.8 dynes/cm2) 10 μM RRx-001 treatment was exacerbated (p = 0.05). In conclusion, we demonstrated that RBCs treated with RRx-001 preferentially aggregate in HEP-G2 and HT-29 tumors, likely due to interactions between RRx-001 and cysteine residues within RBCs. Furthermore, RRx-001 treated RBCs demonstrated increased adhesive potential to endothelial cells upon introduction of TNF-α and hypoxia suggesting that RRx-001 may induce preferential adhesion in the tumor but not in other tissues with endothelial dysfunction due to conditions prevalent in older cancer patients such as heart disease or diabetic vasculopathy.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22094713
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Red Blood Cells: Tethering, Vesiculation, and Disease in Micro-Vascular Flow
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 6 ( 2021-05-27), p. 971-
    Details
    In: Diagnostics, MDPI AG, Vol. 11, No. 6 ( 2021-05-27), p. 971-
    Abstract: The red blood cell has become implicated in the progression of a range of diseases; mechanisms by which red cells are involved appear to include the transport of inflammatory species via red cell-derived vesicles. We review this role of RBCs in diseases such as diabetes mellitus, sickle cell anemia, polycythemia vera, central retinal vein occlusion, Gaucher disease, atherosclerosis, and myeloproliferative neoplasms. We propose a possibly unifying, and novel, paradigm for the inducement of RBC vesiculation during vascular flow of red cells adhered to the vascular endothelium as well as to the red pulp of the spleen. Indeed, we review the evidence for this hypothesis that links physiological conditions favoring both vesiculation and enhanced RBC adhesion and demonstrate the veracity of this hypothesis by way of a specific example occurring in splenic flow which we argue has various renderings in a wide range of vascular flows, in particular microvascular flows. We provide a mechanistic basis for membrane loss and the formation of lysed red blood cells in the spleen that may mediate their turnover. Our detailed explanation for this example also makes clear what features of red cell deformability are involved in the vesiculation process and hence require quantification and a new form of quantitative indexing.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics11060971
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662336-5
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