AI Article Synopsis
Article Abstract
Introduction: The demand for red blood cells (RBCs) is on the rise due to the increasing diagnosis of chronic diseases such as sickle cell anemia, malaria, and thalassemia. Despite many commercial attempts, there are no U.S. FDA-approved artificial RBCs for use in humans. Existing RBC substitutes have employed various strategies to transport oxygen, extend the circulation time, and reduce organ toxicity, but none have replicated the natural protective mechanisms of RBCs, which prevent hemoglobin (Hb) dimerization and heme iron oxidation. (earthworm) erythrocruorin (LtEc) is a naturally occurring extracellular hemoglobin (Hb) with promising attributes: large molecular diameter (30 nm), high molecular weight (3.6 MDa), low auto-oxidation rate, and limited nitric oxide-scavenging properties. These characteristics make LtEc an ideal candidate as an RBC substitute. However, LtEc has a significant drawback, its short circulatory half-life. To address this issue, we explored thiol-mediated surface PEGylation of LtEc (PEG-LtEc) at varying polyethylene glycol (PEG) surface coverages. Increasing PEG surface coverage beyond 40% destabilizes LtEc into smaller subunits that are 1/12th the size of LtEc. Therefore, we evaluated two PEG surface coverage options: PEG-LtEc-0.2 (20% PEGylation) and PEG-LtEc-1.0 (100% PEGylation).
Methods: We conducted experiments using golden Syrian hamsters with dorsal window chambers and catheters to assess the efficacy of these solutions. We measured microvascular parameters, organ function, cerebral blood flow, circulation time, mean arterial pressure, heart rate, and blood gases and performed histology to screen for toxicity.
Conclusion: Our findings indicate that both PEG-LtEc molecules offer significant benefits in restoring microvascular parameters, organ function, cerebral blood flow, and circulation time compared to LtEc alone. Notably, PEG-LtEc-1.0 showed superior microvascular perfusion, although it exhibited a higher rate of auto-oxidation compared to PEG-LtEc-0.2. These results underscore the advantages of PEGylation in terms of tissue perfusion and organ health while highlighting its limitations.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acsabm.4c00273 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hyperbaric Oxygen Therapy Improved Neovascularisation Following Limb Ischaemia-The Role of ROS Mitigation.
J Cell Mol Med
December 2024
Division of Plastic Surgery, Department of Surgery, Chi-Mei Medical Center, Tainan, Taiwan.
Hyperbaric oxygen (HBO) therapy has emerged as a potential treatment, shown to enhance blood flow and angiogenesis. However, specific effects and mechanisms of HBO on limb ischaemia responding to a hypoxic environment remain largely unknown. We aimed to investigate the therapeutic potential of HBO in the treatment of limb ischaemia.
View Article and Find Full Text PDFApplication of Keystone Design Perforator Island Flap in the Reconstruction of Maxillofacial Defect: A Case Series.
Ear Nose Throat J
December 2024
Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
To investigate the effect of Keystone Design Perforator Island Flap (KDPIF) in the repair of maxillofacial soft tissue defect. From June 2021 to June 2023, 16 patients with soft tissue defects caused by resection of maxillofacial tumor repaired by KDPIF were selected. Variants of KDPIF were designed according to the area of the defect, and the incision was parallel to the wrinkle as far as possible in the same facial cosmetic subunit.
View Article and Find Full Text PDFBlood Cytokine Profile in Breast Cancer: Focusing on Differences among Molecular Subtypes.
Iran J Immunol
December 2024
Department of General Surgery, Istanbul Training and Research Hospital, Istanbul, Turkey.
Background: Breast cancer is the leading cause of cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies among different subtypes of breast cancer.
View Article and Find Full Text PDFPilot study on the dynamic interactions between cardiac activity and corneal biomechanics during eye movements.
Front Med (Lausanne)
December 2024
Department of Optics and Photonics, Wrocław University of Science and Technology, Wrocław, Poland.
Background And Objective: The study examines the relationship between ocular rotations and cardiovascular functions through detailed biomechanical analysis. The study documents specific patterns of ocular movements and their synchronization with cardiovascular activity, highlighting significant correlations. These findings provide a basis for understanding the opto-biomechanical interplay between ocular and cardiovascular dynamics.
View Article and Find Full Text PDFAlterations of T Cell Subsets Associated with Sickle Cell Trait.
Blood Genom Discov
October 2024
Department of Pathology and Laboratory Medicine, University of Vermont Larner College of Medicine, Burlington, VT 05405, USA.
Sickle cell trait (SCT) has been associated with alterations in various immune-related laboratory parameters including lower circulating lymphocyte counts. To further characterize the impact of SCT on the immune system, we performed flow cytometry of monocyte and lymphocyte immune cell subsets from peripheral blood mononuclear cells collected in a large, community-based cohort of SCT-positive (n = 68) and SCT-negative (n = 959) Black adults. SCT was significantly associated with lower proportions of CD8 and CD4 T cell subsets that include senescent-like markers of repeated immune system challenges.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!