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Oxygen tension at 50% haemoglobin saturation (P50), which reflects the degree of peripheral oxygen offloading and tissue oxygenation, plays an important role in the diagnosis and treatment of disease, as well as in transfusion research. Blood gas analysers are commonly used in clinical and obtain P50 values through complex calculations and analysis. Oxygenation-dissociation analysers are specially designed to record the oxygen dissociation curves and obtain P50 values of whole blood, red blood cells (RBCs), and stroma-free haemoglobin. However, whether the two equipment obtain comparable data is still uncertain. Herein, we used both equipment to detect P50 values of blood and stroma-free haemoglobin from human and bovine sources, venous and arterial blood of beagle and rat, and stored rat blood. For human blood, both analysers yielded similar data. P50 of the stroma-free haemoglobin and bovine blood could only be properly detected by oxygenation-dissociation analysers. Blood gas analysers showed different P50 values, while oxygenation-dissociation analysers got similar P50 values for arterial and venous samples. Oxygenation-dissociation analysers distinguished changes in P50 values during RBCs storage. Compared with the blood gas analysers, oxygenation-dissociation analysers had a stronger detection capability in P50 measurement with regard to both sample types and species. [ABSTRACT FROM AUTHOR]

Purpose: Chronic kidney disease (CKD) is associated with persistent systemic inflammation. Reduced red blood cell (RBC) survival in patients with CKD has been identified for several decades. The purpose of this study is to explore whether excessive erythrophagocytosis exists and contributes to systemic inflammation in CKD., Patients and Methods: A CKD rat model was induced by 5/6 nephrectomy. Erythrocyte osmotic fragility was determined with hypotonic NaCl solutions. Erythrocyte deformability was evaluated by filterability. RBC cell death was quantified using fluorescence-activated cell sorting analyses of fluorescent annexin V-bound surface phosphatidylserine (PS). Erythrophagocytosis was evaluated in vivo and in vitro. RT-qPCR and immunohistochemistry were used to determine the inflammatory effects after erythrophagocytosis., Results: Erythrocyte osmotic fragility and deformability progressively declined, and the percentage of PS-exposing RBCs progressively increased in CKD rats. Levels of erythrophagocytosis in vivo were evaluated by autologous injection of CFSE-labeled erythrocytes. In comparison with the control group, higher fluorescence intensity of CFSE was detected in the spleen homogenates of rats with CKD. In vitro, more of erythrocytes from 5/6Nx rats were phagocytosed by peritoneal macrophages in comparison to those from control rats. Compared with macrophages phagocytosed control erythrocytes, macrophages phagocytosed CKD erythrocytes exhibited higher mRNA levels of IL-6, CXCL-10, CXCL-11, iNOS, IL-1β, ICAM-1 and MCP-1. Compared with the control group, the red pulp of rats with CKD exhibited higher levels of p-NFκB, IL-6, iNOS and CXCL-10. ELISA results showed significantly increased plasma levels of both IL-6 and CXCL-10 in patients with long-term hemodialysis compared with those in healthy controls (2.30 ± 1.38 pg/mL vs 1.33 ± 0.65 pg/mL, P =0.01; 78.11 ± 27.34 pg/mL vs 37.45 ± 7.08 pg/mL, P =0.001)., Conclusion: Our results indicated that excessive erythrophagocytosis may contribute to systemic inflammation in CKD., Competing Interests: This paper has been uploaded to ResearchSquare as a preprint: https://www.researchsquare.com/article/rs-3767556/latest. The authors report no conflicts of interest in this work., (© 2024 Meng et al.)

Red blood cell substitutes offer a solution to the problem of blood shortage and side effects of blood transfusion. Hemoglobin-based oxygen carriers (HBOCs) are one of the promising substitutes for red blood cells. Vasoactivity, which refers to the side effect of HBOCs that causes vasoconstriction and subsequent hypertension, limits the clinical application of HBOCs. In this study, an ex vivo method for the evaluation of vasoactivity induced by HBOCs was established based on isolated rat mesenteric artery vessels and the DMT120CP system. The DMT120CP system, equipped with a flowmeter, permits the control of intravascular pressure, pressure gradient, and flow conditions with high accuracy, simulating the physiological conditions for isolated vessels. The concentration of noradrenaline was optimized to 1 × 10 -6 ∼3 × 10 -6  M. PEGylated bovine hemoglobin (PEG-bHb) was synthesized and perfused into the vessel for vasoactivity evaluation, with bHb as the positive control and PSS buffer solution as the negative control. PEG-bHb showed a hydration diameter of 15.5 ± 1.4 nm and a P 50 value of 6.99 mmHg. PEG-bHb exhibited a colloid osmotic pressure of 64.1 mmHg and a viscosity of 1.73 cp at 40 mg/mL. The established vasoactivity evaluation method showed significant differences in samples (bHb or PEG-bHb) with different vasoactivity properties. The vasoconstriction percentage induced by PEG-bHb samples synthesized in different batches showed coefficients of variation less than 5%, indicating good applicability and repeatability. The established evaluation method can be applied to study the vasoactivity induction and elimination strategies, promoting the clinical application of HBOCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Gao, You, Li, Wang, Chen and Zhao.)

Background: Alzheimer's disease (AD) is a common progressive neurodegenerative disease. The Ubiquitin-Protease system (UPS), which plays important roles in maintaining protein homeostasis in eukaryotic cells, is involved in the development of AD. This study sought to identify differential UPS-related genes (UPGs) in AD patients by using bioinformatic methods, reveal potential biomarkers for early detection of AD, and investigate the association between the identified biomarkers and immune cell infiltration in AD., Methods: The differentially expressed UPGs were screened with bioinformatics analyses using the Gene Expression Omnibus (GEO) database. A weighted gene co-expression network analysis (WGCNA) analysis was performed to explore the key gene modules associated with AD. A Single-sample Gene Set Enrichment Analysis (ssGSEA) analysis was peformed to explore the patterns of immune cells in the brain tissue of AD patients. Real-time quantitative PCR (RT-qPCR) was performed to examine the expression of hub genes in blood samples from healthy controls and AD patients., Results: In this study, we identified four UPGs ( USP3 , HECW2 , PSMB7 , and UBE2V1 ) using multiple bioinformatic analyses. Furthermore, three UPGs ( USP3 , HECW2 , PSMB7 ) that are strongly correlated with the clinical features of AD were used to construct risk score prediction markers to diagnose and predict the severity of AD. Subsequently, we analyzed the patterns of immune cells in the brain tissue of AD patients and the associations between immune cells and the three key UPGs. Finally, the risk score model was verified in several datasets of AD and showed good accuracy., Conclusions: Three key UPGs are identified as potential biomarker for AD patients. These genes may provide new targets for the early identification of AD patients., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Oxygen tension at 50% haemoglobin saturation (P 50 ), which reflects the degree of peripheral oxygen offloading and tissue oxygenation, plays an important role in the diagnosis and treatment of disease, as well as in transfusion research. Blood gas analysers are commonly used in clinical and obtain P 50 values through complex calculations and analysis. Oxygenation-dissociation analysers are specially designed to record the oxygen dissociation curves and obtain P 50 values of whole blood, red blood cells (RBCs), and stroma-free haemoglobin. However, whether the two equipment obtain comparable data is still uncertain. Herein, we used both equipment to detect P 50 values of blood and stroma-free haemoglobin from human and bovine sources, venous and arterial blood of beagle and rat, and stored rat blood. For human blood, both analysers yielded similar data. P 50 of the stroma-free haemoglobin and bovine blood could only be properly detected by oxygenation-dissociation analysers. Blood gas analysers showed different P 50 values, while oxygenation-dissociation analysers got similar P 50 values for arterial and venous samples. Oxygenation-dissociation analysers distinguished changes in P 50 values during RBCs storage. Compared with the blood gas analysers, oxygenation-dissociation analysers had a stronger detection capability in P 50 measurement with regard to both sample types and species.