The effect of the endothelial surface layer on cell-cell interactions in microvessel bifurcations.

Red blood cells (RBCs) carry oxygen and make up 40-45% of blood by volume in large vessels down to 10% or less in smaller capillaries. Because of their finite size and large volume fraction, they are heterogeneously distributed throughout the body. This is partially because RBCs are distributed or partitioned nonuniformly at diverging vessel bifurcations where blood flows from one vessel into two. Despite its increased recognition as an important player in the microvasculature, few studies have explored how the endothelial surface layer (ESL; a vessel wall coating) may affect partitioning and RBC dynamics at diverging vessel bifurcations. Here, we use a mathematical and computational model to consider how altering ESL properties, as can occur in pathological scenarios, change RBC partitioning, deformation, and penetration of the ESL. The two-dimensional finite element model considers pairs of cells, represented by interconnected viscoelastic elements, passing through an ESL-lined diverging vessel bifurcation. The properties of the ESL include the hydraulic resistivity and an osmotic pressure difference modeling how easily fluid flows through the ESL and how easily the ESL is structurally compressed, respectively. We find that cell-cell interaction leads to more uniform partitioning and greatly enhances the effects of ESL properties, especially for deformation and penetration. This includes the trend that increased hydraulic resistivity leads to more uniform partitioning, increased deformation, and decreased penetration. It also includes the trend that decreased osmotic pressure increases penetration.

A modified low-priming cardiopulmonary bypass system in patients undergoing cardiac surgery with medium risk of transfusion: A randomized controlled trial.

Objectives: The FUWAI-SAVE system is a modified low-priming cardiopulmonary bypass (CPB) system. The study aimed to explore whether the FUWAI-SAVE system can reduce the perioperative blood transfusion and its impact on other postoperative complications during cardiac surgery. Metohds: This study was a single-center, single-blind, randomized controlled trial, registered at the Chinese Clinical Trial Registry (identifier: ChiCTR2100050488). Adult patients undergoing cardiac surgery with CPB and intermediate risk for transfusion risk stratification were randomly assigned to an intervention group (FUWAI-SAVE group) or a control group (conventional group). The primary endpoint of the study was the peri-CPB red blood cell transfusion (RBC) rate. The secondary endpoints included the transfusion rate of other blood products, the amount of blood products transfused, the incidence of major complications, in-hospital mortality, and others. Results: 360 patients were randomized from December 9, 2021, to January 30, 2023. The rate of the primary endpoint was significantly lower in the FUWAI-SAVE group compared to the control group [ OR (95%CI): 0.649 (0.424-0.994)]. Meanwhile, the amount of RBC transfusion during the peri-CPB period was significantly lower in the FUWAI-SAVE group compared to the control group, with a mean difference of -0.626 (-1.176 to -0.076) units. The occurrence rate of major complications did not differ significantly between the two groups. Conclusions: Among adult patients undergoing cardiac surgery with CPB, the application of the FUWAI-SAVE system significantly reduced RBC transfusion rate and amount. The FUWAI-SAVE system can be considered an important component of comprehensive blood management strategies in cardiac surgery.

Impact of red blood cell transfusion and hemoglobin threshold on 1-year mortality among surgical sepsis survivors: A propensity score matching study.

BACKGROUND: Despite the fact that red blood cell (RBC) transfusion is commonly applied in surgical intensive care unit (ICU), the effect of RBC transfusion on long-term outcomes remains undetermined. We aimed to explore the association between RBC transfusion and the long-term prognosis of surgical sepsis survivors. METHODS: This retrospective study was conducted on adult sepsis patients admitted to a tertiary surgical ICU center in China. Patients were divided into transfusion and non-transfusion groups based on the presence of RBC transfusion. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW)were performed to balance the potential confounders. RESULTS: A total of 1421 surgical sepsis survivors were enrolled, including 403 transfused patients and 1018 non-transfused patients. There was a significant difference in 1-year mortality between the two groups (23.1 â€‹% vs 12.7 â€‹%, HR: 1.539, 95 â€‹% confidence interval [CI]: 1.030-2.299, P â€‹< â€‹0.001). After PSM and IPTW, transfused patients still showed significantly increased 1-year mortality risks compared to non-transfused individuals (PSM: 23.6 â€‹% vs 15.9 â€‹%, HR 1.606, 95 â€‹% CI 1.036-2.488 â€‹P â€‹= â€‹0.034; IPTW: 20.1 â€‹% vs 12.9 â€‹%, HR 1.600, 95 â€‹% CI 1.040-2.462 â€‹P â€‹= â€‹0.032). Among patients with nadir hemoglobin below 70 â€‹g/L, 1-year mortality risks in both groups were similar (HR 1.461, 95 â€‹% CI 0.909-2.348, P â€‹= â€‹0.118). However, among patients with nadir hemoglobin above 70 â€‹g/L, RBC transfusion was correlated with increased 1-year mortality risk (HR 1.556, 95 â€‹% CI 1.020-2.374, P â€‹= â€‹0.040). CONCLUSION: For surgical sepsis survivors, RBC transfusion during ICU stay was associated with increased 1-year mortality, especially when patients show hemoglobin levels above 70 â€‹g/L.

Dolutegravir- Versus Efavirenz-Based Treatment in Pregnancy: Impact on Red Blood Cell Folate Concentrations in Pregnant Women and Their Infants.

In IMPAACT 2010/VESTED, pregnant women were randomized to initiate dolutegravir (DTG)+emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG+FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF. We assessed red blood cell folate concentrations (RBC-folate) at maternal study entry and delivery, and infant birth. RBC-folate outcomes were: 1) maternal change entry to delivery (trajectory), 2) infant, 3) ratio of infant-to-maternal delivery. Generalized estimating equation models for each log(folate) outcome were fit to estimate adjusted geometric mean ratio (Adj-GMR)/GMR trajectories (Adj-GMRT) of each arm comparison in 340 mothers and 310 infants. Overall, 90% of mothers received folic acid supplements and 78% lived in Africa. At entry, median maternal age was 25 years, gestational age was 22 weeks, CD4 count was 482 cells/mm3 and log10HIV RNA was 3 copies/mL. Entry RBC-folate was similar across arms. Adj-GMRT of maternal folate was 3% higher in the DTG+FTC/TAF versus EFV/FTC/TDF arm (1.03, 95%CI 1.00, 1.06). The DTG+FTC/TAF arm had an 8% lower infant-maternal folate ratio (0.92, 95%CI 0.78, 1.09) versus EFV/FTC/TDF. Results are consistent with no clinically meaningful differences between arms for all RBC-folate outcomes and they suggest that cellular uptake of folate and folate transport to the infant do not differ in pregnant women starting DTG- vs. EFV-based ART.

Ginseng total saponin improves red blood cell oxidative stress injury by regulating tyrosine phosphorylation and glycolysis in red blood cells.

BACKGROUND: Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PURPOSE: This study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. METHODS: The oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. RESULTS: GTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. CONCLUSIONS: This study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.

Red Blood Cell Alloimmunization in Pregnancy: A Review of the Pathophysiology, Prevalence, and Risk Factors.

This review paper provides an overview of the risk factors and laboratory testing for red blood cell (RBC) alloimmunization in pregnancy. RBC alloimmunization is a significant medical issue that can cause haemolytic disease of the fetus and newborn (HDFN), leading to neonatal morbidity and mortality. Current HDFN prophylaxis targets only Rhesus D (RhD) alloimmunization, with no effective measures to prevent alloimmunization to other RBC antigen groups. Several factors can increase the risk of developing RBC alloimmunization during pregnancy, including fetomaternal haemorrhage, RBC and maternal genetic status, and previous transfusions. Identifying these risk factors is essential to execute the appropriate management strategies to minimize the risk of HDFN. The review also discusses the laboratory methods and overview of pregnancy management. The paper highlights the importance of identifying and managing the risk factors for RBC alloimmunization in pregnancy to minimize the risk of HDFN and improve neonatal outcomes.

Associations of RBC counts and incidence of DVT in patients with spinal cord injury: a five year observational retrospective study.

BACKGROUND: The role of red blood cell (RBC) counts as potential independent risk factors for deep vein thrombosis (DVT) in patients with spinal cord injury (SCI) remains uncertain. This study aims to clarify the associations between RBC counts and DVT incidence among this population. METHODS: A retrospective analysis was performed on 576 patients with SCI admitted to the rehabilitation medicine department from January 1, 2017 to December 31, 2021. After exclusions, 319 patients were analyzed, among which 94 cases of DVT were identified. RESULTS: Mode of injury, D-dimer and anticoagulant therapy were significant covariates (P < 0.05). Age, fibrinogen, D-dimer, anticoagulant therapy and American Spinal Cord Injury Association impairment scale (AIS) grades were associated with RBC counts and DVT incidence (P < 0.05). Adjusting for these factors, a 1.00 × 10^12/L increase in RBC counts correlated with a 45% decrease in DVT incidence (P = 0.042), revealing a "U" shaped relationship with a pivot at 4.56 × 10^12/L (P < 0.05). CONCLUSION: RBC counts below 4.56 × 10^12/L serve as a protective factor against DVT, while counts above this threshold pose a risk. These findings could inform the development of DVT prevention strategies for patients with SCI, emphasizing the need for targeted monitoring and management of RBC counts.

The physiological significance of plasma-accessible carbonic anhydrase in the respiratory systems of fishes.

Carbonic anhydrase (CA) activity is ubiquitously found in all vertebrate species, tissues and cellular compartments. Most species have plasma-accessible CA (paCA) isoforms at the respiratory surfaces, where the enzyme catalyzes the conversion of plasma bicarbonate to carbon dioxide (CO2) that can be excreted by diffusion. A notable exception are the teleost fishes that appear to lack paCA at their gills. The present review: (i) recapitulates the significance of CA activity and distribution in vertebrates; (ii) summarizes the current evidence for the presence or absence of paCA at the gills of fishes, from the basal cyclostomes to the derived teleosts and extremophiles such as the Antarctic icefishes; (iii) explores the contribution of paCA to organismal CO2 excretion in fishes; and (iv) the functional significance of its absence at the gills, for the specialized system of O2 transport in most teleosts; (v) outlines the multiplicity and isoform distribution of membrane-associated CAs in fishes and methodologies to determine their plasma-accessible orientation; and (vi) sketches a tentative time line for the evolutionary dynamics of branchial paCA distribution in the major groups of fishes. Finally, this review highlights current gaps in the knowledge on branchial paCA function and provides recommendations for future work.

Comparison of cell delivery and cell membrane camouflaged PLGA nanoparticles in the delivery of shikonin for colorectal cancer treatment.

Inspired by the "natural camouflage" strategy, cell-based biomimetic drug delivery systems (BDDS) have shown great potential in cancer therapy. Red blood cell (RBC) delivery vehicles and red blood cell membrane (RBCm)-camouflaged vehicles were commonly used strategies for drug delivery. We prepared shikonin-encapsulated PLGA nanoparticles (PLGA/SK) with different surface charges to obtain both RBC delivery and RBCm-camouflaged PLGA NPs. The physicochemical properties, in vivo circulation and antitumor effects of these biomimetic preparations were studied. Since the positive PLGA NPs may affect the morphology and function of RBCs, the biomimetic preparations prepared by the negative PLGA NPs showed better in vitro stability. However, positive PLGA NP-based biomimetic preparations exhibited longer circulation time and higher tumor region accumulation, leading to stronger anti-tumor effects. Meanwhile, the RBC delivery PLGA(+) NPs possessed better in vitro cytotoxicity, longer circulation time and higher tumor accumulation than RBCm-camouflaged PLGA(+) NPs. Collectively, RBC delivery vehicles possessed more potential than RBCm-camouflaged vehicles on drug delivery for tumor treatment, especially with positive NPs-loaded.

Red Blood Cell Distribution Width to Albumin Ratio for Predicting Type I Cardiorenal Syndrome in Patients with Acute Myocardial Infarction: A Retrospective Cohort Study.

Purpose: Red blood cell distribution width to albumin ratio (RAR) is a novel inflammatory biomarker that independently predicts adverse cardiovascular events and acute kidney injury. This study aimed to assess the predictive value of RAR for cardio-renal syndrome type I (CRS-I) risk in acute myocardial infarction (AMI) patients. Patients and methods: This study retrospectively enrolled 551 patients who were definitively diagnosed as AMI between October 2021 and October 2022 at the Affiliated Zhongda Hospital of Southeast University. Participants were divided into two and four groups based on the occurrence of CRS-I and the quartiles of RAR, respectively. Demographic data, laboratory findings, coronary angiography data, and drug utilization were compared among the groups. Logistic regression and receiver operating characteristic curve (ROC) analysis were performed to identify independent risk factors for CRS-I and evaluated the predictive value of RAR for CRS-I. Results: Among the cohort of 551 patients, 103 (18.7%) developed CRS-I. Patients with CRS-I exhibited significantly elevated RAR levels compared to those without the condition, and the incidence of CRS-I correlated with escalating RAR. Univariate and multivariate logistic regression analyses identified RAR as an independent risk factor for CRS-I. ROC curves analysis demonstrated that RAR alone predicted CRS-I with an area under the curve (AUC) of 0.683 (95% CI=0.642-0.741), which was superior to the traditional inflammatory marker C-reactive protein (CRP). Adding the variable RAR to the model for predicting the risk of CRS-I further improved the predictive value of the model from 0.808 (95% CI=0.781-0.834) to 0.825 (95% CI=0.799-0.850). Conclusion: RAR is an independent risk factor for CRS-I, and high levels of RAR are associated with an increased incidence of CRS-I in patients with AMI. RAR emerges as a valuable and readily accessible inflammatory biomarker that may play a pivotal role in risk stratification in clinical practice.

Comparison of the Detection Rate and Specificity of Irregular Red Blood Cell Antibodies Between First-Time Pregnant Women and Women With a History of Multiple Pregnancies Among 18,010 Chinese Women.

Background: There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant women. Methods: Using the microcolumn gel antiglobulin method, 18,010 Chinese women with a history of pregnancy and pregnant women were screened for irregular RBC antibodies, and for those with positive test results, antibody specificity was determined. The detection rate and specificity of irregular RBC antibodies in women with a history of multiple pregnancies (two or more) and first-time pregnant women were determined. Results: In addition to 25 patients who passively acquired anti-D antibodies via an intravenous anti-D immunoglobulin injection, irregular RBC antibodies were detected in 121 (0.67%) of the 18,010 women. Irregular RBC antibodies were detected in 93 (0.71%) of the 13,027 women with a history of multiple pregnancies, and antibody specificity was distributed mainly in the Rh, MNSs, Lewis, and Kidd blood group systems; irregular RBC antibodies were detected in 28 (0.56%) of the 4983 first-time pregnant women, and the antibody specificity was distributed mainly in the MNSs, Rh, and Lewis blood group systems. The difference in the percentage of patients with irregular RBC antibodies between the two groups was insignificant (χ 2 = 1.248, P > 0.05). Of the 121 women with irregular RBC antibodies, nine had anti-Mur antibodies, and one had anti-Dia antibodies; these antibodies are clinically important but easily missed because the antigenic profile of the reagent RBCs that are commonly used in antibody screens does not include the antigens that are recognized by these antibodies. Conclusion: Irregular RBC antibody detection is clinically important for both pregnant women with a history of multiple pregnancies and first-time pregnant women. Mur and Dia should be included in the antigenic profile of reagent RBCs that are used for performing antibody screens in the Chinese population.

Predicting capillary vessel network hemodynamics in silico by machine learning.

Blood velocity and red blood cell (RBC) distribution profiles in a capillary vessel cross-section in the microcirculation are generally complex and do not follow Poiseuille's parabolic or uniform pattern. Existing imaging techniques used to map large microvascular networks in vivo do not allow a direct measurement of full 3D velocity and RBC concentration profiles, although such information is needed for accurate evaluation of the physiological variables, such as the wall shear stress (WSS) and near-wall cell-free layer (CFL), that play critical roles in blood flow regulation, disease progression, angiogenesis, and hemostasis. Theoretical network flow models, often used for hemodynamic predictions in experimentally acquired images of the microvascular network, cannot provide the full 3D profiles either. In contrast, such information can be readily obtained from high-fidelity computational models that treat blood as a suspension of deformable RBCs. These models, however, are computationally expensive and not feasible for extension to the microvascular network at large spatial scales up to an organ level. To overcome such limitations, here we present machine learning (ML) models that bypass such expensive computations but provide highly accurate and full 3D profiles of the blood velocity, RBC concentration, WSS, and CFL in every vessel in the microvascular network. The ML models, which are based on artificial neural networks and convolution-based U-net models, predict hemodynamic quantities that compare very well against the true data but reduce the prediction time by several orders. This study therefore paves the way for ML to make detailed and accurate hemodynamic predictions in spatially large microvascular networks at an organ-scale.

Erythrocyte membrane-camouflaged mesoporous silica composite nanoparticles for loading and controlled release of the hepatoprotective agent silibinin: A-synthesis and physicochemical characterization.

OBJECTIVES: Milk thistle has long been used in the treatment of liver and biliary disorders. In the present study, to make a long-acting delivery system for silibinin (SBN, a major active constituent of milk thistle seeds with antioxidant and hepatoprotective function), mesoporous silica composite nanoparticles (NC) were synthesized and coated with RBC membrane. METHODS: A modified Stöber method was used for NC synthesis, which was then characterized using FE-SEM, DLS, TEM, FTIR, and EDAX techniques. A suitable lysis buffer was used to prepare RBC-ghost, and sonication was used to coat SBN-loaded NC (SBN-NC). The RBC-ghost coated SBN-NC (SBN-NC-RBCG) was evaluated by SDS-PAGE, Bradford, TEM, EDAX, and DLS methods. SBN release was then compared for the SBN-NC and SBN-NC-RBCG samples. KEY FINDINGS: the RBC membrane proteins were recovered from the coating of SBN-NC-RBCG, and SBN release was sustained over 24 h when compared with the SBN-NC. CONCLUSIONS: Overall, through prolonging circulation in the bloodstream and evading the immune system, the developed system can improve SBN bioavailability in liver inflammation and fibrosis conditions that need further research.

Red Cell Distribution Width and Mean Corpuscular Volume Alterations: Detecting Inflammation Early in Occupational Cement Dust Exposure.

Introduction Cement dust emitted during cement manufacture consists of toxic components. Occupational cement dust exposure may cause inflammation in the human body, which may be detected early by observing changes in blood parameters such as red blood cell distribution width (RDW) and mean corpuscular volume (MCV). Objectives The study aims to observe the effect of occupational cement dust exposure on RDW and MCV. Methods This study was performed in the Department of Physiology of Dhaka Medical College, Dhaka, Bangladesh, and a factory in Munshiganj, Bangladesh, from September 2017 to August 2018. Ninety-two participants between 20 and 50 years were included (46 subjects were occupationally exposed to cement dust, and 46 were not exposed to cement dust). A pre-designed questionnaire was used for data collection. An independent sample t-test was used to analyze basic information, such as blood pressure and BMI. The multivariate regression model was used to analyze the effect of cement dust exposure on the study group. The impact of cement dust exposure duration was analyzed using the multivariate regression model. The level of significance was p < 0.05. The statistical analysis was performed using STATA-15 (StataCorp, College Station, TX), and the graphical presentation used GraphPad Prism v8.3.2. Results The cement dust-exposed participants had a significantly higher value of MCV by 1.19 fi (95% CI = 0.02, 4.84; p = 0.049) and a 5.92% increase in RDW (95% CI = 5.29, 6.55; p < 0.001) than that of the control group. Conclusion The study reveals that exposure to cement dust causes significant changes in RDW and MCV. These changes may indicate hemolysis due to inflammation.

Association of thalassemia, hemoglobinopathies, and vitamin D levels with lipid profile in adults: Community-based research in southern Thai population.

This study explored the frequency of lipid-lowering drug use in the thalassemia population and investigated the association of thalassemia, hemoglobinopathies, and serum 25(OH)D levels with lipid profile and red blood cell parameters. A combination of cross-sectional and community-based studies was conducted with 615 participants from the southern Thai population. Thalassemia and hemoglobinopathies were diagnosed using hemoglobin analysis and polymerase chain reaction-based methods to genotype globin genes. Biochemical parameters such as lipid profile, fasting blood sugar (FBS), and serum 25(OH)D levels were assessed using standard enzymatic methods and electrochemiluminescence immunoassays. Differences in the means of hematological and biochemical parameters between the thalassemia and non-thalassemia groups were compared and analyzed. A significantly lower frequency of lipid-lowering drug use was observed in the thalassemia group. Thalassemia, with clearly defined abnormalities in red blood cells, is associated with a 4.72-fold decreased risk of taking lipid-lowering drugs. Among thalassemia participants, the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly lower than those in non-thalassemia participants. The prevalence of hypovitaminosis D in carriers of thalassemia and/or hemoglobinopathies in the southern Thai population was 53 % in females and 21 % in males. The highest lipid profile was observed in samples without thalassemia and hypovitaminosis D. The genetics of thalassemia and hemoglobinopathies with obviously abnormal red blood cells could explain the variable lipid levels, in addition to lipid metabolism-related genes and environmental factors. However, the effect of thalassemia on lipid levels in each population may differ according to its prevalence. A larger sample size is required to confirm this association, especially in countries with a high prevalence of thalassemia.

Novel high molecular weight polymerized hemoglobin in a non-obese model of cardiovascular and metabolic dysfunction.

The widespread adoption of high-calorie, high-fat, high-sucrose diets (HFHSD) has become a global health concern, particularly due to their association with cardiovascular diseases and metabolic disorders. These comorbidities increase susceptibility to severe outcomes from viral infections and trauma, with trauma-related incidents significantly contributing to global mortality rates. This context underscores the critical need for a reliable blood supply. Recent research has focused on high molecular weight (MW) polymerized human hemoglobin (PolyhHb) as a promising alternative to red blood cells (RBCs), showing encouraging outcomes in previous studies. Given the overlap of metabolic disorders and trauma-related health issues, it is crucial to assess the potential toxicity of PolyhHb transfusions, particularly in models that represent these vulnerable populations. This study evaluated the effects of PolyhHb exchange transfusion in guinea pigs that had developed metabolic disorders due to a 12-week HFHSD regimen. The guinea pigs, underwent a 20 % blood volume exchange transfusion with either PolyhHb or the lower molecular weight polymerized bovine hemoglobin, Oxyglobin. Results revealed that both PolyhHb and Oxyglobin transfusions led to liver damage, with a more pronounced effect observed in HFHSD-fed animals. Additionally, markers of cardiac dysfunction indicated signs of cardiac injury in both the HFHSD and normal diet groups following the Oxyglobin transfusion. This study highlights how pre-existing metabolic disorders can exacerbate the potential side effects of hemoglobin-based oxygen carriers (HBOCs). Importantly, the newer generation of high MW PolyhHb showed lower cardiac toxicity compared to the earlier generation low MW PolyhHb, known as Oxyglobin, even in models with pre-existing endothelial and metabolic challenges.

On-Chip Impedance Spectroscopy of Malaria-Infected Red Blood Cells.

Malaria is a disease that affects millions of people worldwide, particularly in developing countries. The development of accurate and efficient methods for the detection of malaria-infected cells is crucial for effective disease management and control. This paper presents the electrical impedance spectroscopy (EIS) of normal and malaria-infected red blood cells. An EIS microfluidic device, comprising a microchannel and a pair of coplanar electrodes, was fabricated for single-cell measurements in a continuous manner. Based on the EIS results, the aim of this work is to discriminate Plasmodium falciparum-infected red blood cells from the normal ones. Different from typical impedance spectroscopy, our measurement was performed for the cells in a low-conductivity medium in a frequency range between 50 kHz and 800 kHz. Numerical simulation was utilized to study the suitability parameters of the microchannel and electrodes for the EIS experiment over the measurement frequencies. The measurement results have shown that by using the low-conductivity medium, we could focus on the change in the conductance caused by the presence of a cell in the sensing electrode gap. The results indicated a distinct frequency spectrum of the conductance between the normal and infected red blood cells, which can be further used for the detection of the disease.

Exogenous polyserine fibrils change membrane properties of phosphatidylcholine-liposome and red blood cells.

The causative genes for neurodegenerative polyglutamine (polyQ) diseases produce homopolymeric polyglutamine (polyQ), polyserine (polyS), polyalanine (polyA), polycysteine (polyC), and polyleucine (polyL) sequences by repeat-associated non-AUG (RAN) translation. The cytotoxicity of the intracellular polyQ and RAN products has been extensively investigated. However, little is known about the toxicity of the extracellular polyQ and RAN products on the membranes of viable cells. Because polyQ aggregates induce a deflated morphology of a model membrane, we hypothesized that extracellular polyQ and RAN products might affect the membrane properties of viable cells. In this study, we demonstrated that exogenous polyS fibrils but not polyS or polyQ non-fibril aggregates altered the thermal phase transition behavior of a model membrane composed of a phosphatidylcholine bilayer using differential scanning calorimetry. PolyS fibrils induced morphological changes in viable red blood cells (RBCs). However, both polyS and polyQ non-fibril aggregates had no effects on RBCs. These results highlight the possibility that extracellular fibrils generated from RAN products may alter the properties of neuronal cell membranes, which may contribute to changes in the brain pathology.

Hypertension Increases Susceptibility to Experimental Malaria in Mice.

Global prevalence of hypertension is on the rise, burdening healthcare, especially in developing countries where infectious diseases, such as malaria, are also rampant. Whether hypertension could predispose or increase susceptibility to malaria, however, has not been extensively explored. Previously, we reported that hypertension is associated with abnormal red blood cell (RBC) physiology and anemia. Since RBC are target host cells for malarial parasite, Plasmodium, we hypothesized that hypertensive patients with abnormal RBC physiology are at greater risk or susceptibility to Plasmodium infection. To test this hypothesis, normotensive (BPN/3J) and hypertensive (BPH/2J) mice were characterized for their RBC physiology and subsequently infected with Plasmodium yoelii (P. yoelii), a murine-specific non-lethal strain. When compared to BPN mice, BPH mice displayed microcytic anemia with RBC highly resistant to osmotic hemolysis. Further, BPH RBC exhibited greater membrane rigidity and an altered lipid composition, as evidenced by higher levels of phospholipids and saturated fatty acid, such as stearate (C18:0), along with lower levels of polyunsaturated fatty acid like arachidonate (C20:4). Moreover, BPH mice had significantly greater circulating Ter119+ CD71+ reticulocytes, or immature RBC, prone to P. yoelii infection. Upon infection with P. yoelii, BPH mice experienced significant body weight loss accompanied by sustained parasitemia, indices of anemia, and substantial increase in systemic pro-inflammatory mediators, compared to BPN mice, indicating that BPH mice were incompetent to clear P. yoelii infection. Collectively, these data demonstrate that aberrant RBC physiology observed in hypertensive BPH mice contributes to an increased susceptibility to P. yoelii infection and malaria-associated pathology.

Successful management of maternal anti-PP1Pk alloimmunization in pregnancy with therapeutic plasma exchange and intravenous immunoglobulin.

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.