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Subarachnoid hemorrhage (SAH) is the deadliest form of hemorrhagic stroke; however, effective therapies are still lacking. Perfluorocarbons (PFCs) are lipid emulsion particles with great flexibility and their much smaller size as compared to red blood cells (RBCs) allows them to flow more efficiently within the blood circulation. Due to their ability to carry oxygen, a specific PFC-based emulsion, PFC-Oxygent, has been used as a blood substitute; however, its role in cerebral blood flow regulation is unknown. Adult C57BL/6 wildtype male mice were subjected to an endovascular perforation model of SAH followed by an intravenous (i.v.) injection of 9 ml/kg PFC-Oxygent or no treatment at 5 h after SAH. At 48 h after SAH, functional and anatomical outcomes were assessed. We found that SAH resulted in significant neurologic and motor deficits which were prevented by PFC-Oxygent treatment. We found that SAH-induced vasospasm, reduced RBC deformability, and augmented endothelial dysfunction were also restricted by PFC-Oxygent treatment. Moreover, mitochondrial activity and fusion proteins were also markedly decreased as assessed by oxidative phosphorylation (OXPHOS) after SAH. Interestingly, PFC-Oxygent treatment brought the mitochondrial activity close to the basal level. Moreover, SAH attenuated the level of phosphorylated AMP-activated protein kinase (pAMPK), whereas PFC treatment improved pAMPK levels. These data show the beneficial effects of PFC-Oxygent in limiting the severity of SAH. Further studies are needed to fully understand the mechanism through which PFC-Oxygent exerts its beneficial effects in limiting SAH severity. [ABSTRACT FROM AUTHOR]

The deformability of human red blood cells (RBCs), which comprise almost 99% of the cells in whole blood, is largely related not only to pathophysiological blood flow but also to the levels of intracellular compounds. Therefore, statistical estimates of the deformability of individual RBCs are of paramount importance in the clinical diagnosis of blood diseases. Although the microscale hydrodynamic interactions of individual RBCs lead to non-Newtonian blood rheology, there is no established method to estimate individual RBC deformability from the rheological data of RBC suspensions, and the possibility of this estimation has not been proven. To address this issue, we conducted an integrated analysis of a model of the rheology of RBC suspensions, coupled with macrorheological data of human RBCs suspended in plasma. Assuming a nonlinear curve of the relative viscosity of the suspensions as a function of the cell volume fraction, the statistical average of the membrane shear elasticity was estimated for individual intact RBCs or hardened RBCs. Both estimated values reproduced well the experimentally observed shear-thinning non-Newtonian behavior in these suspensions. We hereby conclude that our complementary approach makes it possible to estimate the statistical average of individual RBC deformability from macrorheological data obtained with usual rheometric tests. [ABSTRACT FROM AUTHOR]

Hibernation is a widespread and highly efficient mechanism to save energy in mammals. However, one major challenge of hibernation is maintaining blood circulation at low body temperatures, which strongly depends on the viscoelastic properties of red blood cells (RBCs). Here, we examined at physiologically relevant timescales the thermomechanical properties of hundreds of thousands of individual RBCs from the hibernating common noctule bat (Nyctalus noctula), the nonhibernating Egyptian fruit bat (Rousettus aegyptiacus), and humans (Homo sapiens). We exposed RBCs to temperatures encountered during normothermia and hibernation and found a significant increase in elasticity and viscosity with decreasing temperatures. Our data demonstrate that temperature adjustment of RBCs is mainly driven by membrane properties and not the cytosol while viscous dissipation in the membrane of both bat species exceeds the one in humans by a factor of 15. Finally, our results show that RBCs from both bat species reveal a transition to a more viscous-like state when temperature decreases. This process on a minute timescale has an effect size that is comparable with fluctuations in RBC viscoelasticity over the course of the year, implying that environmental factors, such as diets, have a lower impact on the capability of RBCs to respond to different temperatures than general physical properties of the cell membrane. In summary, our findings suggest membrane viscoelasticity as a promising target for identifying mechanisms that could be manipulated to ensure blood circulation at low body temperatures in humans, which may be one first step toward safe synthetic torpor in medicine and space flight. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions The aim of this study is to determine whether there are any changes in hemorheological parameters, including whole blood viscosity (WBV), plasma viscosity, erythrocyte aggregation, and erythrocyte deformability, in acute ischemic stroke patients, and to establish their relationship with stroke etiology. The study also aims to observe the changes in these parameters, if any, over time and after treatment, and to assess the correlation between risk factors for ischemic stroke and neuroimaging findings.This was a prospective observational study including 70 patients diagnosed with acute ischemic stroke within the first 3 days of the onset of symptoms and 96 healthy controls. Stroke patients were categorized based on TOAST criteria, and hemorheological parameters were measured at admission and on the fifth day post‐treatment. Erythrocyte aggregation and deformability were measured using a laser ektacytometer, and viscosity assessment was conducted with a rotational viscometer.Stroke patients exhibited significant differences from the control group in aggregation amplitude, aggregation index, and aggregation half‐time (p = 0.001, p = 0.013, p = 0.009, respectively) and showed elevated maximum value of elongation index (p = 0.000). No significant differences in WBV and plasma viscosity were observed between the groups. Post‐treatment, the small vessel occlusion subgroup demonstrated a notable reduction in WBV. Additionally, homocysteine levels showed a positive correlation with scattered white matter lesions in basal ganglia and infratentorial regions (p = 0.002, p = 0.039, respectively).Increased predisposition to erythrocyte aggregation may contribute to the occurrence of acute ischemic stroke. Moreover, gaining the ability of erythrocytes to deform and increase blood flow may serve as a compensatory mechanism in the chronic vascular disease process. The risk factors for ischemic stroke may exhibit connections to specific areas within the brain. [ABSTRACT FROM AUTHOR]

Several diseases like Sickle Cell Anemia, Thalassemia, Hereditary Spherocytosis, Malaria, and Micro-angiopathic Hemolytic Anemia can alter the normal shape of red blood cells (RBCs). The objective of this study is to gain insight into how a change in RBC deformability can affect blood heat transfer. The heat sink effect in a bifurcated vessel with two asymptotic cases (case 1: deformable and case 2: nondeformable RBCs) is being studied during hyperthermia treatment in a three-dimensional bifurcated vessel, whose wall is being subjected to constant heat flux boundary condition. Euler–Euler multiphase method along with the granular model and Kinetic theory is used to include the particle nature of RBCs during blood flow in the current model. To enhance the efficiency of the numerical model, user-defined functions (UDFs) are imported into the model from the C++ interface. The numerical model used is verified with the experimental results from (Carr and Tiruvaloor, 1989, “Enhancement of Heat Transfer in Red Cell Suspensions In Vitro Experiments,” ASME J. Biomech. Eng., 111(2), pp. 152–156; Yeleswarapu et al. 1998, “The Flow of Blood in Tubes: Theory and Experiment,” Mech. Res. Commun., 25(3), pp. 257–262). The results indicate that the deformability of RBCs can change both the flow dynamics and heat sink effect in a bifurcated vessel, which subsequently affects the efficacy and efficiency of the thermal ablation procedure. Both spatial and transient Nusselt numbers of blood flow with deformable RBCs are slightly higher compared to the one with nondeformable RBCs. [ABSTRACT FROM AUTHOR]

Seminars in Thrombosis and Hemostasis (STH) celebrates 50 years of publishing in 2024. To celebrate this landmark event, STH is republishing some archival material. This article represents the most highly cited paper ever published in STH. The original abstract follows. Blood is a two-phase suspension of formed elements (i.e., red blood cells [RBCs], white blood cells [WBCs], platelets) suspended in an aqueous solution of organic molecules, proteins, and salts called plasma. The apparent viscosity of blood depends on the existing shear forces (i.e., blood behaves as a non-Newtonian fluid) and is determined by hematocrit, plasma viscosity, RBC aggregation, and the mechanical properties of RBCs. RBCs are highly deformable, and this physical property significantly contributes to aiding blood flow both under bulk flow conditions and in the microcirculation. The tendency of RBCs to undergo reversible aggregation is an important determinant of apparent viscosity because the size of RBC aggregates is inversely proportional to the magnitude of shear forces; the aggregates are dispersed with increasing shear forces, then reform under low-flow or static conditions. RBC aggregation also affects the in vivo fluidity of blood, especially in the low-shear regions of the circulatory system. Blood rheology has been reported to be altered in various physiopathological processes: (1) Alterations of hematocrit significantly contribute to hemorheological variations in diseases and in certain extreme physiological conditions; (2) RBC deformability is sensitive to local and general homeostasis, with RBC deformability affected by alterations of the properties and associations of membrane skeletal proteins, the ratio of RBC membrane surface area to cell volume, cell morphology, and cytoplasmic viscosity. Such alterations may result from genetic disorders or may be induced by such factors as abnormal local tissue metabolism, oxidant stress, and activated leukocytes; and (3) RBC aggregation is mainly determined by plasma protein composition and surface properties of RBCs, with increased plasma concentrations of acute phase reactants in inflammatory disorders a common cause of increased RBC aggregation. In addition, RBC aggregation tendency can be modified by alterations of RBC surface properties because of RBC in vivo aging, oxygen-free radicals, or proteolytic enzymes. Impairment of blood fluidity may significantly affect tissue perfusion and result in functional deteriorations, especially if disease processes also disturb vascular properties. [ABSTRACT FROM AUTHOR]

Reduced shear strain and deformability of the thoracolumbar fascia has been linked to low back pain. A number of ultrasound examination methods have been developed for laboratory rather than clinical practice. The aim of this study was to examine the reliability and discriminative validity (patients vs. healthy individuals) of an ultrasound (US) measurement method for the quantification of thoracolumbar fascia deformation (TLFD). A cross-sectional study with US assessment and rater blinding was conducted in a manual therapy clinic and a university laboratory. 16 acute low back pain (aLBP) patients and 15 healthy individuals performed a standardized trunk extension task. US measurements of TLFD were carried out independently by two raters by imaging the TLF in the starting and ending positions of the movement. Intra-rater and inter-rater reliability were calculated using intraclass correlation coefficients (ICCs) and minimal detectable changes (MDC) were calculated. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off for TLFD to discriminate the study groups. Kappa statistics were performed to assess rater agreement in discrimination. Intra-rater reliability was excellent (ICC:.92, MDC: 5.54 mm, p <.001) and inter-rater reliability was good (ICC:.78, MDC: 8.70 mm, p <.001). The cut-off for TLFD was 6 mm with a sensitivity of 100% and a specificity of 93.75% and the raters agreed moderately (κ = 0.74, p <.001) when distinguishing patients and controls. The reliability of the US method for assessing TLFD is moderate to excellent, and the ability to discriminate aLBP patients from healthy individuals is moderate. The method could be used to capture an additional parameter in morphological aLBP screenings. [ABSTRACT FROM AUTHOR]

Collective alignment of cell populations is a commonly observed phenomena in biology. An important example are aligning fibroblasts in healthy or scar tissue. In this work we derive and simulate a mechanistic agent-based model of the collective behaviour of actively moving and interacting cells, with a focus on understanding collective alignment. The derivation strategy is based on energy minimisation. The model ingredients are motivated by data on the behaviour of different populations of aligning fibroblasts and include: Self-propulsion, overlap avoidance, deformability, cell-cell junctions and cytoskeletal forces. We find that there is an optimal ratio of self-propulsion speed and overlap avoidance that maximises collective alignment. Further we find that deformability aids alignment, and that cell-cell junctions by themselves hinder alignment. However, if cytoskeletal forces are transmitted via cell-cell junctions we observe strong collective alignment over large spatial scales. Author summary: Collective dynamics is the study of how the interaction of individual animals, humans, cells, etc. can lead to patterns on a scale much larger than the individuals themselves. Prominent examples are flocking birds, schools of fish or the patterns of bacterial colonies. Since the behaviour of the group is very difficult to intuit from individual interaction rules, mathematical models are invaluable in testing hypotheses, making predictions, and suggesting explanations. In our collaborative work between mathematicians and biologists, we use a mathematical model, whose ingredients are motivated by the experimental observation of fibroblasts. Fibroblasts are cells that are part of the connective tissue in animals and play an important role e.g. in wound healing. Under certain conditions, e.g. in scar tissue or near tumours, these spindle-shaped cells form strongly aligned populations on large spatial scales for unclear reasons. By simulating our mathematical model, we predict how the cells' self-propulsion, overlap avoidance, deformability, and other interactions influence the alignment dynamics. The results help to understand alignment of cell populations and apply to many other cells or organisms. [ABSTRACT FROM AUTHOR]

Aberrant tumor mechanical microenvironment (TMME), featured with overactivated cancer‐associated fibroblasts (CAFs) and excessive extracellular matrix (ECM), severely restricts penetration and accumulation of cancer nanomedicines, while mild‐hyperthermia photothermal therapy (mild‐PTT) has been developed to modulate TMME. However, photothermal agents also encounter the barriers established by TMME, manifesting in limited penetration and heterogeneous distribution across tumor tissues and ending with attenuated efficiency in TMME regulation. Herein, it is leveraged indocyanine green (ICG)‐loaded soft nanogels with outstanding deformability, for efficient tumor penetration and uniform distribution, in combination with mild‐PTT to achieve potent TMME regulation by inhibiting CAFs and degrading ECM. As a result, doxorubicin (DOX)‐loaded stiff nanogels gain greater benefits in tumor penetration and antitumor efficacy than soft counterparts from softness‐mediated mild‐PTT. This study reveals the crucial role of nanomedicine mechanical properties in tumor distribution and provides a novel strategy for overcoming the barriers of solid tumors with soft deformable nanogels. [ABSTRACT FROM AUTHOR]

Blood scarcity is one of the main causes of healthcare disruptions worldwide, with blood shortages occurring at an alarming rate. Over the last decades, blood substitutes have aimed at reinforcing the supply of blood, with several products (e.g., hemoglobin (Hb)‐based oxygen (O2) carriers, perfluorocarbons (PFC)) achieving a limited degree of success. Regardless, there is still no widespread solution to this problem due to persistent challenges in product safety and scalability. In this Review, different advances are described in the field of blood substitution, particularly in the development of artificial red blood cells, otherwise known as engineered erythrocytes (EE). The different strategies are categorized into natural, synthetic, or hybrid approaches, and discuss their potential in terms of safety and scalability. Synthetic EEs are identified as the most powerful approach, and describe erythrocytes from a materials engineering perspective. Their biological structure and function are reviewed, as well as explore different methods of assembling a material‐based cell. Specifically, it is discussed how to recreate size, shape, and deformability through particle fabrication, and how to recreate the functional machinery through synthetic biology and nanotechnology. It is concluded by describing the versatile nature of synthetic erythrocytes in medicine and pharmaceuticals and propose specific directions for the field of erythrocyte engineering. [ABSTRACT FROM AUTHOR]

“Slow flow” is one very important concept in modern fundamental and clinical biomedicine. Slow coronary flow is indicative of delayed filling of the terminal coronary artery vessels, occurring in the absence of significant coronary stenosis. This group patient of patients exhibits a high incidence of disability and represents a significant financial and material burden for the state and the healthcare system in general.The primary objective of our study was to examine patients with slow coronary flow.We studied the standard parameters recommended by the international health care system (electrocardiography (by Medica QRS-12, Germany), through the electrical activity of a patient’s heart by the electrical impulses (beating) of the heart; HC1(Germany); coagulogramma by Coatron M1 (Germany), troponin by AQT 90 (Germany); general blood test we used automatic human counting device HC1(Germany). Also, we investigate the original parameters (non-standard parameters, which we use in this pilot study) that we were first studied for this diagnosis and non-standard parameters.A general blood test showed that patients with slow flow had a higher blood leukocyte count than the control group, but the amount of hemoglobin was normal, the hematocrit was much higher than in the control group, and the platelet count was close to the lower limit of clinical standards.We obtained details of blood flow by coagulation situation, such as prothrombin time, prothrombin index, international normalized ratio, activated partial thromboplastin time, thrombin time, fibrinogen, and rheological properties such as index of erythrocyte aggregability, index of erythrocyte deformability, plasma viscosity, in silico blood rheological index.Blood flow can be considered as a superposition of vortices with similar frequencies and wave vectors that change after bifurcations or other obstacles in the vascular network. These factors together determine the conditions for structuring the flow of moving blood. Disruption or alteration of these factors results in slow flow. It has been found that the speed of blood flow in the coronary arteries depends on changes in the number and function of red blood cells. Slow flow is directly influenced by the aggregation and deformation of red blood cells, their number, and plasma viscosity. Consequently, the rheological status plays a crucial role in determining blood flow and its velocity. [ABSTRACT FROM AUTHOR]

Nebulized inhalation offers a noninvasive method for delivering drugs to treat both local respiratory and systemic diseases. In this study, insulin was used as a model drug to design a series of deformable nanovesicles (DNVs) with key quality attributes, including particle size, deformability, and drug load capacity. We investigated the effects of these properties on aerosol generation, macrophage phagocytosis, and bloodstream penetration. The results showed that deformability improved nebulization performance and reduced macrophage phagocytosis, benefiting local and systemic delivery. However, the advantage of DNVs for transmembrane penetration was not evident in the alveolar epithelium. Within the size range of 80–490 nm, the smaller the particle size of IPC-DNVs, the easier it is to evade clearance by macrophages and the more effective the in vivo hypoglycemic efficacy will be. In the drug load range of 3–5 mg/mL, a lower drug load resulted in better hypoglycemic efficacy. The area above the blood glucose decline curve with time (AAC) of nebulized DNVs was 2.32 times higher than that of the insulin solution, demonstrating the feasibility and advantages of DNVs in the pulmonary delivery of biomacromolecule drugs. This study provides insights into the construction and formulation optimization of pulmonary delivery carriers. [ABSTRACT FROM AUTHOR]

Background and Aims: Cardiopulmonary bypass (CPB) and circulatory arrest (CA) can induce intestinal injury and consequently lead to multiple organ dysfunction. Nitric oxide (NO) has protective effects, but its effect on the intestine has not been studied. The study aimed to investigate intestinal injury variables and prove the intestinal protective effects of exogenous nitric oxide when modelling CPB and CA in an experiment. Methods: The study was performed on sheep (n = 24). There were four groups: CPB, CPB + NO, CPB + CA and CPB + CA + NO. Sheep in NO groups received intraoperative inhalation of NO at a dose of 80 ppm. Groups without NO underwent CPB and CA without NO delivery. Defaecation rate, dynamics of intestinal fatty acid binding protein (i-FABP), coefficient of microviscosity and polarity in the areas of lipid--lipid and protein-lipid interactions of erythrocyte membranes were assessed. One hour after CPB, the intestinal tissue was collected and assessed for tissue concentrations of adenosine triphosphate (ATP) and lactate. Results: The defaecation rate after CPB was higher in the CPB + NO group than in the CPB group. The concentration of i-FABP after CPB was lower in the CPB + NO and CPB + CA + NO groups than in the CPB and CPB + CA groups. Erythrocyte deformability before and after CPB revealed no significant dynamics in groups with NO. The ATP concentration 1 h after CPB was higher in the CPB + NO group than in the CPB group. The morphological picture in groups with NO was better. Conclusion: When modelling CPB and CA, NO had a positive effect on the functional and structural state of the intestine and also maintained erythrocyte deformability. [ABSTRACT FROM AUTHOR]

Understanding the shear-induced dilatancy of rock fractures is important for assessing the permeability evolution and seismic hazard in shale and geothermal reservoirs. The displacement dependence of fracture dilation has been well studied, while the influence of slip velocity is poorly constrained. In this study, we combined displacement- and velocity-dependent aperture models to reproduce the transient shear-induced dilatancy of fractures in sandstone in 16 normal stress unloading tests. Our results show that the combined aperture model can describe the transient fracture aperture evolution during accelerating slip induced by normal stress unloading better than the model dependent only on slip displacement. Slip velocity could enhance the aperture increase on smoother fractures at lower normal stresses and higher slip velocities. Both the dilation factor and characteristic slip distance decrease with increasing normal stress and surface roughness, signifying reduced contribution of slip velocity to transient shear-induced dilatancy at higher normal stresses and surface roughness. The dilation angle increases with the increase of surface roughness, and this increase diminishes at higher normal stresses primarily attributable to more severe asperity wear. These findings highlight the importance of slip velocity in controlling the transient evolution of aperture and permeability of a rock fracture. Our study also provides constraints on the constitutive parameters in the combined aperture model for describing transient shear-induced fracture dilatancy. We suggest that it is crucial to incorporate the velocity-dependent aperture model to simulate the nonlinear evolution of fracture aperture in future analytical and numerical models involving coupled hydromechanical processes in geoenergy systems. [ABSTRACT FROM AUTHOR]

Comparative analysis of erythrocyte deformability in individuals with Diabetes Mellitus (DM) and healthy individuals (Control) was represented, focusing on the Elongation index (EI) calculation based on diffraction images. While no statistically significant differences in EI values were observed between the groups, we determined specific points along the deformability curve and revealed the first derivative of deformability curve (dEI / dSS) as a potential metric for quantifying erythrocyte response to deformation, where SS represents shear stress in Pa (Pascal). Statistically significant differences in dEI / dSS at the half maximum value of the deformability curve were identified, suggesting a slower erythrocyte response to shear stress in DM patients. Scatter plot analysis demonstrated a linear declining trend in dEI / dSS index with an increase in shear stress, indicating decaying erythrocyte responsiveness to higher shear stress values, particularly pronounced in DM patients. Although pilot, this study suggests that dEI / dSS can provide valuable insights into the hemorheological aspects of DM pathology and contribute to a comprehensive understanding of erythrocyte mechanobiological behavior in response to varying shear stress levels. Correlations between the proposed measure of RBC mechanical properties and established clinical markers of DM and its complications (serum cholesterol, creatinine, and urea level) are obtained to get preliminary insight into dEI / dSS application for better diagnosis and/or patient management. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) transfusions facilitate many life-saving acute and chronic interventions. Transfusions are enabled through the gold-standard hypothermic storage of RBCs. Today, the demand for RBC units is unfulfilled, partially due to the limited storage time, 6 weeks, in hypothermic storage. This time limit stems from high metabolism-driven storage lesions at +1-6 °C. A recent and promising alternative to hypothermic storage is the supercooled storage of RBCs at subzero temperatures, pioneered by our group. Here, we report on long-term supercooled storage of human RBCs at physiological hematocrit levels for up to 23 weeks. Specifically, we assess hypothermic RBC additive solutions for their ability to sustain supercooled storage. We find that a commercially formulated next-generation solution (Erythro-Sol 5) enables the best storage performance and can form the basis for further improvements to supercooled storage. Our analyses indicate that oxidative stress is a prominent time- and temperature-dependent injury during supercooled storage. Thus, we report on improved supercooled storage of RBCs at −5 °C by supplementing Erythro-Sol 5 with the exogenous antioxidants, resveratrol, serotonin, melatonin, and Trolox. Overall, this study shows the long-term preservation potential of supercooled storage of RBCs and establishes a foundation for further improvement toward clinical translation. This study explores the premise of extended – up to 23 weeks – supercooled storage of human red blood cells in modern and traditional hypothermic additive solutions and the impact of antioxidant supplementation, in comparison to hypothermic storage. [ABSTRACT FROM AUTHOR]

Accurate mechanical measurements of cells has the potential to improve diagnostics, therapeutics and advance understanding of disease mechanisms, where high-resolution mechanical information can be measured by deforming individual cells. Here we evaluate recently developed techniques for measuring cell-scale stiffness properties; while many such techniques have been developed, much of the work examining single-cell stiffness is impacted by difficulties in standardization and comparability, giving rise to large variations in reported mechanical moduli. We highlight the role of underlying mechanical theories driving this variability, and note opportunities to develop novel mechanotyping devices and theoretical models that facilitate convenient and accurate mechanical characterisation. Moreover, many highthroughput approaches are confounded by factors including cell size, surface friction, natural population heterogeneity and convolution of elastic and viscous contributions to cell deformability. We nevertheless identify key approaches based on deformability cytometry as a promising direction for further development, where both high-throughput and accurate single-cell resolutions can be realized. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cell (hPSC)-derived red blood cells (RBCs) possess great potential for compensating shortages in transfusion medicine. For better RBC generation from hPSCs, we compared the cell seeding density in the embryoid body formation-based hPSC induction protocol. In the selection of low- and high-density inoculation conditions, we found that low-density culture performed better in the final RBC product with more cell output and increased average cellular hemoglobin content. An elaborate study using flow cytometry demonstrated that low inoculation density promoted endothelial-to-hematopoietic transition, followed by improved hematopoietic progenitor formation and erythrocyte generation. The improved transformation from glycolysis to mitochondrial oxidation and reduced apoptosis might be responsible for this effect. Hints from RNA sequencing suggested that molecules involved in microenvironment interaction and metabolic regulation might respond for the different developmental potential. The possible mediators between outer message and intracellular response could be the nutrition sensors FOXO, PRKAA1 (AMPK), and MTOR genes. It is possible that low inoculation density triggered metabolic regulation signals, promoted mitochondrial oxidation, and resulted in enhanced cell amplification and hematopoietic differentiation. The low cell culture density will improve RBC generation from hPSCs. [ABSTRACT FROM AUTHOR]

α-Synuclein (α-Syn) is a protein related to synucleinopathies with high expression in the central nervous system and erythrocytes which are a major source of peripheral α-Syn. Recent reports have suggested the presence of α-Syn within extracellular vesicles (EVs) derived from erythrocytes, potentially contributing to the pathogenesis of synucleinopathies. While Lewy bodies, intracellular inclusions containing aggregated α-Syn, are prominently observed within the brain, their occurrence in peripheral neurons implies the dissemination of synucleinopathy pathology throughout the body via the propagation of α-Syn. In this study, we found erythrocytes and circulating EVs obtained from plasma contained α-Syn, which was separated into four major forms using high-resolution clear native-PAGE and isoelectric focusing. Notably, erythrocyte α-Syn was classified into full-length and C-terminal truncated forms, with truncation observed between Y133 and Q134 as determined by LC–MS/MS analysis. Our finding revealed that C-terminally truncated α-Syn, which was previously reported to exist solely within the brain, was also present in erythrocytes and circulating EVs obtained from plasma. [ABSTRACT FROM AUTHOR]

The deformability of red blood cells (RBCs), expressing their ability to change their shape as a function of flow-induced shear stress, allows them to optimize oxygen delivery to the tissues and minimize their resistance to flow, especially in microcirculation. During physiological aging and blood storage, or under external stimulations, RBCs undergo metabolic and structural alterations, one of which is hemoglobin (Hb) redistribution between the cytosol and the membrane. Consequently, part of the Hb may attach to the cell membrane, and although this process is reversible, the increase in membrane-bound Hb (MBHb) can affect the cell's mechanical properties and deformability in particular. In the present study, we examined the correlation between the MBHb levels, determined by mass spectroscopy, and the cell deformability, determined by image analysis. Six hemoglobin subunits were found attached to the RBC membranes. The cell deformability was negatively correlated with the level of four subunits, with a highly significant inter-correlation between them. These data suggest that the decrease in RBC deformability results from Hb redistribution between the cytosol and the cell membrane and the respective Hb interaction with the cell membrane. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hemorheological parameters have been reported to be altered in cardiovascular disease. Major depression has been associated with increased risk of cardiovascular disease. OBJECTIVE: Our hypothesis is that hemorheological parameters are disturbed in major depressive disorder. METHODS: Major depressive disorder and control groups consisted of 50 subjects. Plasma viscosity, erythrocyte aggregation, erythrocyte deformability, hematological parameters and hematological parameters were examined. RESULTS: Plasma viscosity was statistically significantly higher, erythrocyte elongation index at 0.53 Pa and 0.95 Pa was lower, and MCV, MCH, and MCHC values were also lower in the major depression group (P < 0.05). Elongation index and plasma viscosity were correlated with depressive symptomatology. CONCLUSIONS: The increased plasma viscosity and decreased elongation index of erythrocytes indicate an unfavorable hemorheological situation in patients with major depressive disorder compared with healthy controls. The results of this study confirm the findings of studies finding a potential threat to cardiovascular health from major depressive disorder. Increased plasma viscosity and decreased erythrocyte elongation index in depressed patients may be risk factors for cardiovascular events and provide data on the causality of the association between depression and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Our group generated two induced pluripotent stem cell (iPSC) lines for in vitro red blood cell (RBC) production from blood donors with extensively known erythrocyte antigen profiles. One line was intended to give rise to RBCs for transfusions in patients with sickle cell disease (SCD), while the other was developed to create RBC panel reagents. Two blood donors were selected based on their RBC phenotypes, further complemented by high-throughput DNA array analysis to obtain a more comprehensive erythrocyte antigen profile. Enriched erythroblast populations from the donors' peripheral blood mononuclear cells were reprogrammed into iPSCs using nonintegrative plasmid vectors. The iPSC lines were characterized and subsequently subjected to hematopoietic differentiation. iPSC PB02 and iPSC PB12 demonstrated in vitro and in vivo iPSC features and retained the genotype of each blood donor's RBC antigen profile. Colony-forming cell assays confirmed that iPSC PB02 and iPSC PB12 generated hematopoietic progenitors. These two iPSC lines were generated with defined erythrocyte antigen profiles, self-renewal capacity, and hematopoietic differentiation potential. With improvements in hematopoietic differentiation, these cells could potentially be more efficiently differentiated into RBCs in the future. They could serve as a complementary approach for obtaining donor-independent RBCs and addressing specific demands for blood transfusions. [ABSTRACT FROM AUTHOR]

Fabric‐reinforced shape memory polymer composites are lightweight, strong, formable, controllable, and suitable for various engineering and innovative applications. This study aims to fabricate and characterize electrothermal dual drive shape memory polymer composite fabrics (SMPCFs) of different densities with three‐dimensional (3D) angle‐interlock structures. The tensile properties, electrothermal properties, recovery forces (both tensile and bending), and shape recovery properties of SMPCFs were evaluated. The SMPCFs exhibited a tensile elongation of over 20% at the transition temperature. SMPCFs can reach transition temperatures when loaded with 2 V. The recovery forces are up to 225 N in tensile recovery force and 3.6 N in bending recovery force. In the shape recovery test, the recovery ratio exceeded 97%. Finally, the demonstration of recovery properties can stimulate the possibilities of SMPCFs in innovation and applications. Highlights: Core‐shell structured composite filaments were prepared.3D angle‐interlock composite fabrics: high strength, electrothermal drive.Tensile recovery force of composite fabrics can be up to 225 N.Elongation at transition temperatures was up to 20%. [ABSTRACT FROM AUTHOR]

BACKGROUND: The triad "insulin resistance, prediabetes, diabetes" is three independent neologies with characteristic features and development. In addition, each are characterized by progression and the possibility of transition from one form to other. Due to the fact that diabetes is one of the common diseases associated with high rates of disability, it is necessary to improve diagnostic methods and educational regimens for successful prevention and treatment of the disease. OBJECTIVE: We investigated Band 3 protein (B3p) level, osmotic resistance of erythrocytes, the total antioxidant activity (TAA) of blood serum, level of HbA1 in group patients with insulin resistance (IR), prediabetes, and Type 2 Diabetes Mellitus (T2DM) and comparative with health control group. METHODS: We used original, accurate research methods that measure the essence of the studied quantities. RESULTS: Disruptions of glucose and insulin homeostasis ay lead to the initiation of oxidative stress (in our study demonstrated by a decrease of TAA of blood serum) increased redox-sensitive PTP activity and aberrant band 3 phosphorylation, potentially leading to reduced erythrocyte deformability. At the same time glycation of Hb during T2DM may affect its cross-link with membrane proteins, in particular with B3p, and although appears to limit its cross-linking and decrease its clusterization ability, induces alterations in the cytoskeletal matrix, and thereby decrease erythrocytes' osmotic resistance making them more susceptible to hemolysis. CONCLUSIONS: The osmotic resistance of the erythrocytes can be used as a sensitive marker for the detection of the early stages of hyperglycemia (prediabetes). This set of clinical trials will make it possible to identify diseases that make up the triad at an early stage. Early detection of disorders and continued research in this direction will help in the development of a diagnostic scheme for the prevention of such patients. Based on our data, research into anti-oxidation drugs is very important. With the help of the array of studies described in the article and antioxidant treatment, the likelihood of successful treatment will increase. [ABSTRACT FROM AUTHOR]

The current paper is aimed to investigate the deformability effects of the bearing surface on the lubrication performance of cylindrical journal bearing with finite length under turbulent conditions. The bush is coated with a thin resilient layer with a smooth surface, the radial distortions of which are of the same order of magnitude as the film thickness. The elastohydrodynamic problem is studied under elasticity conditions in accordance with the plain strain hypothesis (Winkler model). The modified Reynolds equation is carried out on the base of the turbulent lubrication model of Hirs (bulk flow model). The partial differential equation is solved numerically by successive over-relaxation technique on a finite difference grid, considering different values of coating materials, lubricant viscosity, and journal speed. Results for the performance characteristics of the bearing are given for several selected values of Reynolds number and elasticity parameters of the soft liner on the bush. [ABSTRACT FROM AUTHOR]

Measurements of neutron star mass and radius or tidal deformability deliver unique insight into the equation of state (EOS) of cold dense matter. EOS inference is very often done using generalized parametric or non-parametric models, which deliver no information on composition. In this paper, we consider a microscopic nuclear EOS model based on a field theoretical approach. We show that current measurements from NICER and gravitational wave observations constrain primarily the symmetric nuclear matter EOS. We then explore what could be delivered by measurements of mass and radius at the level anticipated for future large-area X-ray timing telescopes. These should be able to place very strong limits on the symmetric nuclear matter EOS, in addition to constraining the nuclear symmetry energy that determines the proton fraction inside the neutron star. [ABSTRACT FROM AUTHOR]

Cold water immersion (CWI) involves rapid cooling of the body, which, in healthy individuals, triggers a defence response to an extreme stimulus, to which the body reacts with stress. The aim of the study was to determine the effect of CWI on hemorheological blood indicators. The study group consisted of 13 young males. Blood samples were collected before and after CWI. The assessed parameters included the complete blood count, fibrinogen, hs-C-reactive protein (CRP), proteinogram, and blood rheology factors, such as erythrocyte elongation index (EI), half-time of total aggregation, and aggregation index. Additionally, the effect of reduced temperature on primary human vascular endothelium was investigated in vitro. CWI resulted in the decrease of body temperature to 31.55 ± 2.87 °C. After CWI, neutrophil count and mean corpuscular volume (MCV) were significantly increased in the study group, while lymphocyte count was significantly decreased. Significantly higher levels of total blood protein and albumin concentration were detected after the immersion. Among hemorheological characteristics, erythrocyte EIs at shear stress values ranging from 2.19 to 60.30 Pa were significantly lower after CWI. No significant changes in other rheological, morphological or biochemical parameters were observed. In vitro, human umbilical vein endothelial cells responded to 3 h of temperature decrease to 25 °C with unchanged viability, but increased recruitment of THP-1 monocytic cells and changes in cell morphology were observed. This was the first study to evaluate the effect of single CWI on rheological properties of blood in healthy young men. The results indicate that a single CWI may increase blood protein concentrations and worsen erythrocyte deformability parameters. [ABSTRACT FROM AUTHOR]

Introduction: Equations can calculate pulse wave velocity (ePWV) from blood pressure values (BP) and age. The ePWV predicts cardiovascular events beyond carotid-femoral PWV. We aimed to evaluate the correlation between four different equations to calculate ePWV. Methods: The ePWV was estimated utilizing mean BP (MBP) from office BP (MBPOBP) or 24-hour ambulatory BP (MBP24-hBP). We separated the whole sample into two groups: individuals with risk factors and healthy individuals. The e-PWV was calculated as follows: e 1 − P W V = 9.58748315543126 − 0.402467539733184 * age + 4.56020798207263 * 10 − 3 * age 2 − 2.6207705511664 * 10 − 5 *age 2 * MBP + 3.1762450559276 * 10 − 3 * age * MBP − 1.83215068503821 * 10 − 2 * MBP e 2 − P W V = 4.62 − 0.13 * age + 0.0018 * age 2 + 0.0006 * age * MBP + 0.0284 * MBP We calculated the concordance correlation coefficient (Pc) between e1-PWVOBP vs e2-PWVOBP, e1-PWV24-hBP vs e2-PWV24-hBP, and mean values of e1-PWVOBP, e2-PWVOBP, e1-PWV24-hBP and e2-PWV24-hBP. The multilevel regression model determined how much the ePWVs are influenced by age and MBP values. Results: We analyzed data from 1541 individuals; 1374 ones with risk factors and 167 healthy ones. The values are presented for the entire sample, for risk-factor patients and for healthy individuals respectively. The correlation between e1-PWVOBP with e2-PWVOBP and e1-PWV24-hBP with e2-PWV24-hBP was almost perfect. The Pc for e1-PWVOBP vs e2-PWVOBP was 0.996 (0.995–0.996), 0.996 (0.995–0.996), and 0.994 (0.992–0.995); furthermore, it was 0.994 (0.993–0.995), 0.994 (0.994–0.995), 0.987 (0.983–0.990) to the e1-PWV24-hBP vs e2-PWV24-hBP. There were no significant differences between mean values (m/s) for e1-PWVOBP vs e2-PWVOBP 8.98±1.9 vs 8.97±1.8; p = 0.88, 9.14±1.8 vs 9.13±1.8; p = 0.88, and 7.57±1.3 vs 7.65±1.3; p = 0.5; mean values are also similar for e1-PWV24-hBP vs e2-PWV24-hBP, 8.36±1.7 vs 8.46±1.6; p = 0.09, 8.50±1.7 vs 8.58±1.7; p = 0.21 and 7.26±1.3 vs 7.39±1.2; p = 0.34. The multiple linear regression showed that age, MBP, and age2 predicted more than 99.5% of all four e-PWV. Conclusion: Our data presents a nearly perfect correlation between the values of two equations to calculate the estimated PWV, whether utilizing office or ambulatory blood pressure. [ABSTRACT FROM AUTHOR]

Toxicity caused by carbon tetrachloride (CCl4) can lead to serious liver injury. The aim of the study is to investigate the protective effects of oregano oil (Origanum minutiflorum extract oil) against CCl4‐induced liver injury. Two doses of oregano oil were used in the experiment: a low dose (LD; 20 mg/kg) and a high dose (HD; 60 mg/kg) during 2 weeks. CCl4 caused severe liver damage, nucleolus destruction in hepatocytes and cytogenetic changes in the nucleus. Indirectly, CCl4 causes decreased protein synthesis and significantly high creatinine and urea values. Hematological disorders have been recorded, such as decreased RBC and hemoglobin concentration, increased WBC and deformability of the erythrocyte membrane. Both doses of oregano oil had protective effects. Improved protein synthesis and high globulins level, creatinine and urea were found in both groups. Cytogenetic changes in the nucleus of hepatocytes were reduced. A high dose of oregano oil had maximal protective effects for RBC, but a very weak effect on hemoglobin synthesis. Also, WBC and lymphocyte values were low. Origanum stimulates protein synthesis and recovery of hepatocytes after liver injury, reduces the deformability of the erythrocyte membrane. High doses of oregano oil decreased WBC and lymphocytes which may lead to a weakening of the immune response. However, high doses are more effective against severe platelet aggregation than low doses, suggesting an effective treatment against thrombocytosis. Significance statement: Oregano oil extract is a powerful antioxidant and is hepatoprotective. High doses had strong effects against carbon tetrachloride‐induced thrombocytosis, but significantly lowered leukocytes and lymphocytes, which can lead to weakened immunity. For the maximum effect of oreiganum oil, it is necessary to determine the optimal doses and daily intake. This study will contribute to the literature in terms of the discovery of possible effects of oregano oil treatment in pathology related to liver injury and hematological disorders. [ABSTRACT FROM AUTHOR]

In severe cases, SARS-CoV-2 infection leads to severe respiratory failure. Although angiotensin-converting enzyme 2 (ACE2) receptors are not expressed in red blood cells, SARS-CoV-2 can interact with red blood cells (RBCs) via several receptors or auxiliary membrane proteins. Recent data show that viral infection causes significant damage to the RBCs, altering their morphology, deformability, and aggregability. Loss of RBC deformability and/or increased aggregability favors the development of thrombotic processes in the microcirculation, as has been described to occur in COVID-19 patients. In addition, many patients also develop systemic endotheliitis associated with generalized coagulopathy. This manifests itself clinically as obstructive microthrombi in the area of the medium and smallest vessels, which can affect all internal organs. It is thought that such changes in the RBCs may contribute to the microangiopathy/microthrombosis associated with COVID-19 and may result in impaired capillary blood flow and tissue oxygenation. [ABSTRACT FROM AUTHOR]

In this paper, Polyethylene Terephthalate Glycol (PETG) has been used as a novel thermoplastic thermo-responsive Shape Memory Polymer (SMP) with biocompatibility, excellent printability, cost efficiency, and transparency for the 3D/4D printing of porous structures by material extrusion. The high deformability of PETG allows for programming without an increase in temperature or the need for additional operations. This enabled the use of PETG for the Cold Programming (CP) of ordered porous shape memory structures, made possible by material extrusion printing technology. The porous samples were printed employing three patterns and two porosity percentages. The programming operation was performed at ambient temperature by applying different amounts of pre-strains under constrained and unconstrained compression modes. The constrained test was conducted using a mandrel and a matrix for exerting pure volume reduction (pure packing). The shape recovery test was accomplished above the glass transition temperature (Tg), and the fixity and recovery ratios were recorded. Employing 3D printing provided the ability to manufacture porous thermoplastic SMP structures with highly controllable pores geometry and sizes for different porosity percentages. The results showed that the combination of the uniform strain distribution in the porous structures with the help of the 3D printing process and CP on the new PETG SMP makes it possible to achieve high deformation in the glassy region, resulting in a complete shape recovery for two lozenge and vertical patterns. Among all specimens, constrained specimens by horizontal pattern had the highest fixity ratio of 90.7%. However, low fixity ratios in CP can be justified considering the existence of two stages of spring-back and structural relaxation after unloading, resulting from the elastic and viscoelastic behavior. Increasing Infill Density (ID) along with the constrained test (pure packing) improved the shape fixity. The existence of higher mechanical constraints and harsher localized deformation are speculated to be the case for this observation. Applying higher deformations (40 to 80%), for both designed tests, brought about a weakness in the shape memory performance, while it improved for 100% volume reduction. [ABSTRACT FROM AUTHOR]

Absorption spectra of red blood cell (RBC) suspensions are investigated in an osmolarity range in the medium from 200 mOsm to 900 mOsm. Three spectral parameters are used to characterize the process of swelling or shrinkage of RBC—the absorbance at 700 nm, the Soret peak height relative to the spectrum background, and the Soret peak wavelength. We show that with an increase in the osmolarity, the absorbance at 700 nm increases and the Soret peak relative height decreases. These changes are related to the changes in the RBC volume and the resulting increase in the hemoglobin intracellular concentration and index of refraction. Confocal microscopy and flow cytometry measurements supported these conclusions. The maximum wavelength of the Soret peak increases with increasing osmolarity due to changes in the oxygenation state of hemoglobin. Using these spectrum parameters, the process of osmosis in RBCs can be followed in real time, but it can also be applied to various processes, leading to changes in the volume and shape of RBCs. Therefore, we conclude that UV–Vis absorption spectrophotometry offers a convenient, easily accessible, and cost-effective method to monitor changes in RBC, which can find applications in the field of drug discovery and diagnostics of RBC and hemoglobin disorders. [ABSTRACT FROM AUTHOR]

SCD is a hereditary disorder caused by genetic mutation in the beta-globin gene, resulting in abnormal hemoglobin, HbS that forms sickle-shaped erythrocytes under hypoxia. Patients with SCD have endocrine disorders and it was described that 7% of these patients have clinical hypothyroidism. Recent studies have shown that mature erythrocytes possess TSH receptors. Thus, we aimed to assess the effects of TSH on SCD erythrocytes. The experiments were conducted using different concentrations of TSH (1, 2, 3, and 5 mIU/L). In HbS polymerization assay, erythrocytes were exposed to TSH in hypoxia to induce polymerization, and measurements were taken for 30 minutes. The deformability assay was made using Sephacryl-S 500 columns to separate deformable from nondeformable cells. Static adhesion test utilized thrombospondin to assess erythrocyte adhesion in the presence of TSH. TSH at all contractions were able to reduce polymerization of HbS and increase deformability. The static adhesion of erythrocytes at the lowest concentrations of 1 and 2 mIU/L were increased, but at higher contractions of 3 and 5 mIU/L, static adhesion was not modulated. The results suggest that TSH has potential involvement in the pathophysiology of sickle cell disease by inhibiting HbS polymerization, positively modulating deformability and impacting static adhesion to thrombospondin. [ABSTRACT FROM AUTHOR]

Lipid bilayer membranes such as liposomes have been utilized as platforms for bioinspired artificial photosynthesis. Embedding functional compounds, including chromophores and catalysts, into two‐dimensional lipid membranes allows their high local concentration and proximity, resulting in enhanced reactivity compared to that of homogeneous solutions. The control of photoreactions by the physical and chemical properties of membranes, such as fluidity and phase separation, has also been well studied in recent years. In contrast, it remains difficult to control chemical reactions via dynamic membrane deformation. Here, we report on the control of excitation energy transfer using red blood cell ghosts (RBCGs) as scaffolds, relying on their asymmetric lipid membranes and inherent and unique deformability. RBCGs, in which donor and acceptor molecules were chemically conjugated to a two‐dimensional cytoskeleton located beneath the inner membrane, exhibited energy transfer, and their efficiency varied depending on the amount and ratio of donor and acceptor modifications, as confirmed by experimental and theoretical analysis. Furthermore, the KCl concentration‐induced RBCG shrinkage enhanced the energy transfer efficiency. Our proposed method is expected to facilitate the construction of photoreaction systems that can be controlled via membrane deformation. [ABSTRACT FROM AUTHOR]

Exposure to both oxidative and shear stress, a condition that the red blood cell (RBC) continuously experiences in the circulation in vivo can be mimicked in a Couette type viscometer and monitored by ektacytometry. RBCs maintain their deformation and orientation under shear stress and oxidative stress until a threshold is reached at which these conditions appear to overwhelm the elaborate and complex pathways that maintain a proper redox environment in the cell. Oxidative stress under shear alters the ability of the cell to deform, changes cell morphology, its orientation in the shear stress field, and appears to alter intracellular and membrane characteristics. The application of the RoxyScan technology allows the comparison of oxidant effects and the role of antioxidant systems. This provides the opportunity to study the ability of RBC to deal with oxidative stress in various conditions, including RBC disorders such as sickle cell disease (SCD). [ABSTRACT FROM AUTHOR]

Intracellular signaling mechanisms in red blood cells (RBCs) involve various protein kinases and phosphatases and enable rapid adaptive responses to hypoxia, metabolic requirements, oxidative stress, or shear stress by regulating the physiological properties of the cell. Protein phosphorylation is a ubiquitous mechanism for intracellular signal transduction, volume regulation, and cytoskeletal organization in RBCs. Spectrin‐based cytoskeleton connects integral membrane proteins, band 3 and glycophorin C to junctional proteins, ankyrin and Protein 4.1. Phosphorylation leads to a conformational change in the protein structure, weakening the interactions between proteins in the cytoskeletal network that confers a more flexible nature for the RBC membrane. The structural organization of the membrane and the cytoskeleton determines RBC deformability that allows cells to change their ability to deform under shear stress to pass through narrow capillaries. The shear stress sensing mechanisms and oxygenation‐deoxygenation transitions regulate cell volume and mechanical properties of the membrane through the activation of ion transporters and specific phosphorylation events mediated by signal transduction. In this review, we summarize the roles of Protein kinase C, cAMP‐Protein kinase A, cGMP‐nitric oxide, RhoGTPase, and MAP/ERK pathways in the modulation of RBC deformability in both healthy and disease states. We emphasize that targeting signaling elements may be a therapeutic strategy for the treatment of hemoglobinopathies or channelopathies. We expect the present review will provide additional insights into RBC responses to shear stress and hypoxia via signaling mechanisms and shed light on the current and novel treatment options for pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Plant-derived chemicals are promising substances to control arthropod pests, although synthetic ones are still the most frequently used. Thus, comparative toxicological studies are needed to determine if natural substances are safe alternatives to replace the use of synthetic chemicals. This study aimed to compare the toxicity of carvacrol (natural origin), acetylcarvacrol (semi-synthetic) and a fipronil-based pesticide (synthetic). We assessed the effects of these chemicals on hemolytic activity, erythrocytes morphology and leucocyte viability using whole blood from human subjects. Additionally, DNA damage was evaluated through comet and DNA fragmentation assays. Fipronil and carvacrol caused hemolysis at concentrations ranging from 0.5 to 2.0%, whereas acetylcarvacrol did not cause hemolysis at 0.5 and 0.75%. Fipronil and carvacrol caused severe alterations in erythrocytes' morphology at 2%, such as ghost erythrocytes, elliptocyte-like shape and rouleau-like shape, presenting only 3.3 and 8.3% normal cells, respectively, at this concentration. However, 73.3% erythrocytes incubated with 2% acetylcarvacrol exhibited normal morphology. Fipronil considerably reduced leucocytes viability, decreasing it to 78% at 2%. Carvacrol and acetylcarvacrol showed no differences in leucocyte viability for 0.5 to 1.0%, but a decrease was observed for 2% carvacrol. The comet assay showed similar DNA damage for fipronil and carvacrol, but it was significantly lower for 1 and 2% acetylcarvacrol. Incubation with genomic DNA showed that only fipronil caused fragmentation of this molecule. Thus, we conclude that carvacrol and fipronil can present similar toxicity at higher concentrations. However, acetylation of carvacrol significantly reduced its toxicity to human blood cells compared with the other chemicals. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sand therapy is a non-pharmacological physiotherapy method that uses the natural environment and resources of Xinjiang to treat through the heat transfer and magnetic effects of sand. OBJECTIVE: Employing the two-phase flow-Casson blood flow model, we investigate the mechanism of atherosclerosis prevention via sand therapy, offering a biomechanical theoretical rationale for the prevention of atherosclerosis through sand therapy via the prism of computational fluid dynamics (CFD). METHODS: Sand therapy experiments were conducted to obtain popliteal artery blood flow velocity, and blood was considered as a two-phase flow composed of plasma and red blood cells, and CFD method was applied to analyze the hemodynamic effects of Casson's blood viscosity model before and after sand therapy. RESULTS: (1) The blood flow velocity increased by 0.24 m/s and 0.04 m/s at peak systolic and diastolic phases, respectively, after sand therapy; the axial velocity of blood vessels increased by 28.56% after sand therapy. (2) The average red blood cell viscosity decreased by 0.00014 Pa ⋅ s after sand therapy. (3) The low wall shear stress increased by 1.09 Pa and the high wall shear stress reached 41.47 Pa after sand therapy. (4) The time-averaged wall shear stress, shear oscillation index and relative retention time were reduced after sand therapy. CONCLUSION: The increase of blood flow velocity after sand therapy can reduce the excessive deposition of cholesterol and other substances, the decrease of erythrocyte viscosity is beneficial to the migration of erythrocytes to the vascular center, the increase of low wall shear stress has a positive effect on the prevention of atherosclerosis, and the decrease of time-averaged wall shear stress, shear oscillation index and relative retention time can reduce the occurrence of thrombosis. [ABSTRACT FROM AUTHOR]

Combined radiation with hemorrhage (combined injury, CI) exacerbates hematopoietic acute radiation syndrome and mortality compared to radiation alone (RI). We evaluated the effects of RI or CI on blood cell depletion as a biomarker to differentiate the two. Male CD2F1 mice were exposed to 8.75 Gy γ-radiation (60Co). Within 2 h of RI, animals were bled under anesthesia 0% (RI) or 20% (CI) of total blood volume. Blood samples were collected at 4–5 h and days 1, 2, 3, 7, and 15 after RI. CI decreased WBC at 4–5 h and continued to decrease it until day 3; counts then stayed at the nadir up to day 15. CI decreased neutrophils, lymphocytes, monocytes, eosinophils, and basophils more than RI on day 1 or day 2. CI decreased RBCs, hemoglobin, and hematocrit on days 7 and 15 more than RI, whereas hemorrhage alone returned to the baseline on days 7 and 15. RBCs depleted after CI faster than post-RI. Hemorrhage alone increased platelet counts on days 2, 3, and 7, which returned to the baseline on day 15. Our data suggest that WBC depletion may be a potential biomarker within 2 days post-RI and post-CI and RBC depletion after 3 days post-RI and post-CI. For hemorrhage alone, neutrophil counts at 4–5 h and platelets for day 2 through day 7 can be used as a tool for confirmation. [ABSTRACT FROM AUTHOR]

The ability to change shape is essential for the proper functioning of red blood cells (RBCs) within the microvasculature. The shape of RBCs significantly influences blood flow and has been employed in microfluidic lab-on-a-chip devices, serving as a diagnostic biomarker for specific pathologies and enabling the assessment of RBC deformability. While external flow conditions, such as the vessel size and the flow velocity, are known to impact microscale RBC flow, our comprehensive understanding of how their shape-adapting ability is influenced by channel confinement in biomedical applications remains incomplete. This study explores the impact of various rectangular and square channels, each with different confinement and aspect ratios, on the in vitro RBC flow behavior and characteristic shapes. We demonstrate that rectangular microchannels, with a height similar to the RBC diameter in combination with a confinement ratio exceeding 0.9, are required to generate distinctive well-defined croissant and slipper-like RBC shapes. These shapes are characterized by their equilibrium positions in the channel cross section, and we observe a strong elongation of both stable shapes in response to the shear rate across the different channels. Less confined channel configurations lead to the emergence of unstable other shape types that display rich shape dynamics. Our work establishes an experimental framework to understand the influence of channel size on the single-cell flow behavior of RBCs, providing valuable insights for the design of biomicrofluidic single-cell analysis applications. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is considered to be one of the hematological malignancies formed by excessive and abnormal proliferation of plasmocytes. Among other parameters, several blood tests are used to diagnose multiple myeloma. The hemorheological profile in multiple myeloma is not widely studied. Hemorheology includes the study of measuring the deformability and aggregation of erythrocytes, blood viscosity, and sedimentation rate. The degree of deformability of blood cells is necessary to maintain proper vital functions. Proper deformability of red blood cells ensures proper blood circulation, tissue oxidation and carbon dioxide uptake. The aim of the study was to compare morphology and blood rheology parameters in patients with MM and healthy individuals. The study included 33 patients with MM, and 33 healthy subjects of the same age. The hematological blood parameters were evaluated using ABX MICROS 60 hematology analyzer. The LORCA Analyzer to study erythrocyte aggregation and deformability. Patients with MM had lower red blood cells count (RBC) (9.11%) (p < 0.001) and half time of total aggregation (T1/2) (94.29%) (p < 0.001) values and higher mean corpuscular volume (MCV) (5.50%) (p < 0.001), aggregation index (AI) (68.60%) (p < 0.001), total extent of aggregation (AMP) (87.92%) (p < 0.001) values than the healthy control group. Aggregation in patients with MM is different compared to healthy individuals. It was observed that the percentage of cell aggregation is almost 50% higher than in the control group. The study of morphology, aggregation and deformability of erythrocytes in patients with suspected MM may be helpful in making clinical decisions. [ABSTRACT FROM AUTHOR]

Rosetting, the formation of red blood cell aggregates, is a life-threatening condition in malaria tropica and not yet fully understood. We study rosette stability using a set of microfluidic stenotic channels, with varied narrowing angle and erythrocytes of blood groups O and A. We find reduced ability of a rosette to pass a stenosis without disruption, the longer the tapered part of the constriction and the narrower the stenosis is. In general, this ability increases with rosette size and is 5–15% higher in blood group A. The experimental results are substantiated by equivalent experiments using lectin-induced red blood cell aggregates and a simulation of the underlying protein binding kinetics. [ABSTRACT FROM AUTHOR]

Plasmodium parasites need to find red blood cells (RBCs) that, on the one hand, expose receptors for the pathogen ligands and, on the other hand, maintain the right geometry to facilitate merozoite attachment and entry into the red blood cell. Both characteristics change with the maturation of erythrocytes. Some Plasmodia prefer younger vs. older erythrocytes. How does the life evolution of the RBC affect the invasion of the parasite? What happens when the RBC ages? In this review, we present what is known up until now. [ABSTRACT FROM AUTHOR]

This document is an editorial introducing a special issue on advances in red blood cell research. The collection of articles covers a range of topics, including molecular mechanisms of pathologies, novel diagnostic approaches, case studies, epidemiological studies, and transfusion medicine. The articles explore factors influencing red blood cell production, rheological properties of red blood cells, and the use of red blood cells as biomarkers for various diseases. The document also discusses the potential for functional tests and technological advancements in red blood cell research. Additionally, it highlights the importance of in vitro culturing and preservation of red blood cells for transfusion purposes. The authors express their satisfaction with the completion of the issue and look forward to future developments in the field. [Extracted from the article]

The protein 4.1R is an essential component of the erythrocyte membrane skeleton, serving as a key structural element and contributing to the regulation of the membrane's physical properties, including mechanical stability and deformability, through its interaction with spectrin–actin. Recent research has uncovered additional roles of 4.1R beyond its function as a linker between the plasma membrane and the membrane skeleton. It has been found to play a crucial role in various biological processes, such as cell fate determination, cell cycle regulation, cell proliferation, and cell motility. Additionally, 4.1R has been implicated in cancer, with numerous studies demonstrating its potential as a diagnostic and prognostic biomarker for tumors. In this review, we provide an updated overview of the gene and protein structure of 4.1R, as well as its cellular functions in both physiological and pathological contexts. [ABSTRACT FROM AUTHOR]

Since the discovery of physical peculiarities around transcription start sites (TSSs) and a site corresponding to the TATA box, research has revealed only the average features of these sites. Unsettled enigmas include the individual genes with these features and whether they relate to gene function. Herein, using 10 physical properties of DNA, including duplex DNA free energy, base stacking energy, protein-induced deformability, and stabilizing energy of Z-DNA, we clarified for the first time that approximately 97% of the promoters of 21,056 human protein-coding genes have distinctive physical properties around the TSS and/or position −27; of these, nearly 65% exhibited such properties at both sites. Furthermore, about 55% of the 21,056 genes had a minimum value of regional duplex DNA free energy within TSS-centered ±300 bp regions. Notably, distinctive physical properties within the promoters and free energies of the surrounding regions separated human protein-coding genes into five groups; each contained specific gene ontology (GO) terms. The group represented by immune response genes differed distinctly from the other four regarding the parameter of the free energies of the surrounding regions. A vital suggestion from this study is that physical-feature-based analyses of genomes may reveal new aspects of the organization and regulation of genes. [ABSTRACT FROM AUTHOR]

In this study, we numerically investigate the collision dynamics of core–shell compound droplet pairs under confined shear flow conditions. We focus on three collision modes: pass-over, coalescence, and reverse-back motions, analyzing their motion trajectories and morphological evolution. Notably, the coalescence mode exhibits significant dynamic behavior during evolution. However, the coalescence behavior of compound droplet pairs, as well as the impact of geometric parameters, including the initial vertical offset of droplets and the degree of confinement, on their dynamic behaviors, remains largely unexplored and unquantified. Our simulation results reveal that core droplets have little effect on the trajectory of droplet pairs during their pass-over and reverse-back motions, yet they significantly affect the dynamics in the coalescence mode. Additionally, we have addressed how the interplay between the core-shell size ratio, initial offset, and wall confinement affects the transition between collision modes, morphology, trajectory, and final state of the droplet pairs. Our findings show that an increase in the core–shell size ratios restricts the deformability of the shell droplets. Furthermore, in the coalescence mode, larger core droplets coalesce more rapidly due to spatial adjustment, expediting the stabilization of the newly formed compound droplet. While the size of the core droplets does not alter the transition boundary from coalescence to reverse-back mode based on initial vertical offset, they significantly influence the transition from coalescence to pass-over mode. Moreover, by analyzing confinement as another crucial geometric factor, we demonstrate the coupling effects of confinement and initial vertical offset on the transition between different collision modes. [ABSTRACT FROM AUTHOR]

In this study, Trifluralin (TRF) co-loaded with Miltefosine (MTF) in nano transfersomes (NTs) were prepared aiming their enhanced penetration topically with improved macrophage targeting and antileishmanial effects. Formulations were optimized in a series of experiments based on their particle size, polydispersity index (PDI), drug incorporation and deformability index. TEM analysis was performed to check morphology of NTs. TRF-MTF co-loaded NTs were further incorporated into chitosan gel to obtain better retention. In vitro release and Ex vivo permeation studies of the optimized TRF-MTF co-loaded NTs were conducted to check dissolution behavior and skin permeation of the developed formulation as compared to the drug solutions and TRF-MTF co-loaded NTs gel. Macrophage uptake and antileishmanial efficacy of the developed formulation was also investigated. The optimized formulation had a particle size of 188.5 nm with rounded morphology, PDI of 0.101, and deformability index of 0.987. The drug incorporation of TRF and MTF were respectively found as 91% and 88%. Controlled and significantly enhanced drug release and augmented skin penetration was observed from the TRF-MTF co-loaded NTs as compared to pure drugs. Significant uptake of the TRF-MTF co-loaded NTs by the macrophage proved greater intracellular infiltration via the skin barriers. In vitro anti-leishmanial study exhibited 6-folds and 5-folds decrease in the respective IC50 values of TRF-MTF co-loaded NTs when used against Leishmania (L.) tropica amastigotes and promastigotes. This study exhibited the efficacy of NTs when loaded with dual drugs for enhanced skin penetration and macrophage localization. [ABSTRACT FROM AUTHOR]

Medical planning for space exploration is based on the "floating" blood bank model to store life-saving red blood cells (RBCs) for emergencies. The "floating" blood bank approach is not sufficient in cases where multiple crewmembers are affected by space anemia. In these situations, long-term preserved RBCs will be vital to guarantee the health and safety of crew members. Transfusable RBC units can only be refrigerated for 42 days or frozen at −80 °C. However, storing frozen RBCs at −80 °C is challenging during the confined condition of long-duration space flight. Freeze-dried, viable RBCs would be an appropriate alternative because they can be stored without cooling, are predicted to have a shelf-life of years, and could be transfused immediately after rehydration. This study explores if freeze-dried RBCs can be rehydrated and transfused in reduced gravity with similar outcomes in recovery as observed at Earth gravity. Experiments analyzing freeze-dried RBC recoveries, rehydration fluid dynamics, and transfusion flow rates were analyzed utilizing an experimental glovebox in simulated 0 g during parabolic flights. RBC recoveries and rehydration fluid dynamics for volumes of 5 mL and 10 mL were the same in simulated 0 g compared to results obtained at 1 g. A clinically acceptable range of flow rates for slow intravenous infusion and rapid fluid resuscitation was possible with the simple augmentation of a hand-pumped clinical pressure bag around a unit of rehydrated RBCs. The results demonstrate the potential feasibility of using freeze-dried cells for healthcare during deep-space exploration. • Rehydration of freeze-dried biologicals is feasible during simulated reduced gravity. • Freeze-dried red blood cells recovered in microgravity remain morphologically intact. • A syringe-based rehydration system minimized changes in fluid dynamics in reduced gravity. • Pressure sleeves generate clinically acceptable ranges of flow rates for transfusions in 0 g. [ABSTRACT FROM AUTHOR]