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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]

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]

Pathological processes often change the mechanical properties of cells. Increased rigidity could be a marker of cellular malfunction. Erythrocytes are a type of cell that deforms to squeeze through tiny capillaries; changes in their rigidity can dramatically affect their functionality. Furthermore, differences in the homeostatic elasticity of the cell can be used as a tool for diagnosis and even for choosing the adequate treatment for some illnesses. More accurate types of equipment needed to study biomechanical phenomena at the single-cell level are very costly and thus out of reach for many laboratories around the world. This study presents a simple and low-cost technique to study the rigidity of red blood cells (RBCs) through the application of electric fields in a hand-made microfluidic chamber that uses a capacitor principle. As RBCs are deformed with the application of voltage, cells are observed under a light microscope. From mechanical force vs. deformation data, the elastic constant of the cells is determined. The results obtained with the capacitor-based method were compared with those obtained using optical tweezers, finding good agreement. In addition, P. falciparum-infected erythrocytes were tested with the electric field applicator. Our technique provides a simple means of testing the mechanical properties of individual cells. [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]

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]

Performing cardiac surgery under cardiopulmonary bypass (CPB) and circulatory arrest (CA) provokes the development of complications caused by tissue metabolism, microcirculatory disorders, and endogenous nitric oxide (NO) deficiency. This study aimed to investigate the potential mechanisms for systemic organoprotective effects of exogenous NO during CPB and CA based on the assessment of dynamic changes in glycocalyx degradation markers, deformation properties of erythrocytes, and tissue metabolism in the experiment. A single-center prospective randomized controlled study was conducted on sheep, n = 24, comprising four groups of six in each. In two groups, NO was delivered at a dose of 80 ppm during CPB ("CPB + NO" group) or CPB and CA ("CPB + CA + NO"). In the "CPB" and "CPB + CA" groups, NO supply was not carried out. NO therapy prevented the deterioration of erythrocyte deformability. It was associated with improved tissue metabolism, lower lactate levels, and higher ATP levels in myocardial and lung tissues. The degree of glycocalyx degradation and endothelial dysfunction, assessed by the concentration of heparan sulfate proteoglycan and asymmetric dimethylarginine, did not change when exogenous NO was supplied. Intraoperative delivery of NO provides systemic organoprotection, which results in reducing the damaging effects of CPB on erythrocyte deformability and maintaining normal functioning of tissue metabolism. [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 presence of dark matter (DM) within neutron stars (NSs) can be introduced by different accumulation scenarios in which DM and baryonic matter (BM) may interact only through the gravitational force. In this work, we consider asymmetric self-interacting bosonic DM, which can reside as a dense core inside the NS or form an extended halo around it. It is seen that depending on the boson mass ( m χ ), self-coupling constant (λ) and DM fraction ( F χ ), the maximum mass, radius and tidal deformability of NSs with DM admixture will be altered significantly. The impact of DM causes some modifications in the observable features induced solely by the BM component. Here, we focus on the widely used nuclear matter equation of state (EoS) called DD2 for describing NS matter. We show that by involving DM in NSs, the corresponding observational parameters will be changed to be consistent with the latest multi-messenger observations of NSs. It is seen that for m χ ≳ 200 MeV and λ ≲ 2 π , DM-admixed NSs with 4 % ≲ F χ ≲ 20 % are consistent with the maximum mass and tidal deformability constraints. [ABSTRACT FROM AUTHOR]

This document discusses the molecular mechanisms of oxidative stress and the role of antioxidants in protecting against cell damage. It highlights the importance of natural antioxidants found in foods for promoting better health and quality of life. The document also explores the effects of oxidative stress on various physiological processes, such as metabolic pathologies, immune senescence, cellular aging, and cardiovascular diseases. Additionally, it presents research on the potential therapeutic benefits of specific antioxidants in treating oxidative stress-related diseases. The authors hope that this collection of scientific publications will contribute to the understanding of oxidative stress-related disease pathophysiology and the development of antioxidant strategies for disease prevention and treatment. [Extracted from the article]

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]

Enrichment of erythrocytes is a necessary step in the diagnosis of blood diseases. Due to the high deformability and viscosity of erythrocytes, they cannot be regarded as stable point-like solids, so the influence of their deformability on fluid dynamics must be considered. Therefore, by using the special effect of an I-shaped pillar (I-pillar) on erythrocytes, erythrocytes with different deformability can be made to produce different provisional distances in the chip, so as to achieve the separation of the two kinds of erythrocytes. In this study, a microfluidic chip was designed to conduct a control test between erythrocytes stored for a long time and fresh erythrocytes. At a specific flow rate, the different deformable erythrocytes in the chip move in different paths. Then, the influence of erythrocyte deformability on its movement trajectory was analyzed by two-dimensional finite element flow simulation. DLD sorting technology provides a new method for the sorting and enrichment of diseased erythrocytes. [ABSTRACT FROM AUTHOR]

Background: Regular exercise elicits adaptive changes in several organs and physiological processes, including erythrocyte properties. Methods: In a group of 79 subjects (62 men and 17 women; mean age 31.37 ± 10.19 years) who trained several times a week as they practiced amateur sports, we evaluated the elongation index, markers of erythrocyte deformability, red blood cell distribution width (RDW), indicators of erythrocyte anisocytosis, hematocrit, hemoglobin, and the main erythrocyte indices (MCV, MCH, MCHC) in basal conditions. Results: In comparison with a group of healthy, but not training, volunteers, the values of the elongation index, and not the RDW, are increased, and this datum is accompanied by an increase in MCV and MCHC, likely related to an increased presence of circulating young erythrocytes in training subjects. We also divided the same group according to the median of the VO2max, observing that the subgroup above the median shows both an increase in the elongation index values and a decrease in MCH and MCHC. Conclusions: In trained subjects, there is no correlation between the values of the elongation index and the RDW, while the interrelations among the elongation index, RDW, and main erythrocyte indices appear to be of particular interest and of a certain complexity. [ABSTRACT FROM AUTHOR]

High temperature and humidity affect the tribological performance of nitrile butadiene rubber (NBR) seals, which affects the precise positioning of cylinder systems. Therefore, it is crucial to study the effect of hydrothermal aging on the tribological performance of the NBR seals. In this study, the changes in the tribological performance of the NBR seals under hydrothermal aging conditions were investigated. The results show that the volatilization of additives and the increase in crosslink density of the NBR seals occurs in the hydrothermal aging environment, leading to the deterioration of their surface quality, elastic deformability, and tribological performance. The formation of surface micropores due to additive volatilization is the main factor in the degradation of tribological performance. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) has been linked to cell damage and chronic disease development; however, the study of psychological factors related with OS has been limited, as has its relationship with biochemical and personal variables. Therefore, the aim of this study was to evaluate the association between a wide variety of personal, psychological, and biochemical factors with OS in a sample of healthy Mexican people. A total of 134 participants, from which 70 (52%) were women, without known chronic conditions were included in the study, and the molecule 8-hydroxy-2′-deoxyguanosine (8-OHdG) was also measured as a marker of OS. We observed in the multivariate analysis of the whole sample that depressive symptoms (measured with CES-D scale) were the only psychological variable significantly associated (positively) with 8-OHdG. In addition, the following sociodemographic variables were associated with 8-OHdG: age, schooling (positively correlated), and the frequency of vitamins/antioxidant consumption (negatively correlated). The biochemical variables of erythrocytes in urine and amylase were positively correlated with 8-OHdG, while glucose was negatively correlated with it. Additional biochemical variables were associated in the multivariate analysis of each sex, including the positive correlation of LDL-cholesterol, LDH enzyme, lymphocytes, and the negative correlation of phosphorus and eosinophils in women's samples, as well as the positive correlation of potassium, uric acid, and leucocytes in urine and the negative correlation of erythrocytes and lipase in the men's samples. In conclusion, depression was the only psychological variable positively correlated with 8-OHdG after adjusting for confounders, and new associations with biochemical variables were found with some differences between sexes. [ABSTRACT FROM AUTHOR]

The hematological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important in COVID-19 pathophysiology. However, the interactions of SARS-CoV-2 with platelets and red blood cells are still poorly understood. There are conflicting data regarding the mechanisms and significance of these interactions. The aim of this review is to put together available data and discuss hypotheses, the known and suspected effects of the virus on these blood cells, their pathophysiological and diagnostic significance, and the potential role of platelets and red blood cells in the virus's transport, propagation, and clearance by the immune system. We pay particular attention to the mutual activation of platelets, the immune system, the endothelium, and blood coagulation and how this changes with the evolution of SARS-CoV-2. There is now convincing evidence that platelets, along with platelet and erythroid precursors (but not mature erythrocytes), are frequently infected by SARS-CoV-2 and functionally changed. The mechanisms of infection of these cells and their role are not yet entirely clear. Still, the changes in platelets and red blood cells in COVID-19 are significantly associated with disease severity and are likely to have prognostic and pathophysiological significance in the development of thrombotic and pulmonary complications. [ABSTRACT FROM AUTHOR]

The proper regeneration of vessel anastomoses in microvascular surgery is crucial for surgical safety. Pituitary adenylate cyclase-activating polypeptide (PACAP) can aid healing by decreasing inflammation, apoptosis and oxidative stress. In addition to hematological and hemorheological tests, we examined the biomechanical and histological features of vascular anastomoses with or without PACAP addition and/or using a hemostatic sponge (HS). End-to-end anastomoses were established on the right femoral arteries of rats. On the 21st postoperative day, femoral arteries were surgically removed for evaluation of tensile strength and for histological and molecular biological examination. Effects of PACAP were also investigated in tissue culture in vitro to avoid the effects of PACAP degrading enzymes. Surgical trauma and PACAP absorption altered laboratory parameters; most notably, the erythrocyte deformability decreased. Arterial wall thickness showed a reduction in the presence of HS, which was compensated by PACAP in both the tunica media and adventitia in vivo. The administration of PACAP elevated these parameters in vitro. In conclusion, the application of the neuropeptide augmented elastin expression while HS reduced it, but no significant alterations were detected in collagen type I expression. Elasticity and tensile strength increased in the PACAP group, while it decreased in the HS decreased. Their combined use was beneficial for vascular regeneration. [ABSTRACT FROM AUTHOR]

Erythrocytes are responsible for the transport of oxygen within the organism, which is particularly important for nerve tissues. Erythrocyte quality has been shown to be deteriorated in oxidative stress conditions. In this study, we measured the same series of oxidative stress markers in plasma and erythrocytes to compare the differences between neurotypical children (controls) and children with autism spectrum disorder (ASD). We also focused on erythrocyte properties including their deformability, osmotic resistance, Na,K-ATPase activity, nitric oxide levels and free radical levels in children with ASD and controls. Greater oxidative damage to proteins and lipids was observed in the erythrocytes than in the plasma of ASD subjects. Additionally, antioxidant enzymes were more active in plasma samples from ASD children than in their erythrocytes. Significantly higher nitric oxide level and Na,K-ATPase enzyme activity were detected in erythrocytes of ASD individuals in comparison with the controls. Changes in oxidative status could at least partially contribute to the deterioration of erythrocyte morphology, as more frequent echinocyte formation was detected in ASD individuals. These alterations are most probably responsible for worsening the erythrocyte deformability observed in children with ASD. We can conclude that abnormalities in antioxidant status and erythrocyte properties could be involved in the pathomechanisms of ASD and eventually contribute to its clinical manifestations. [ABSTRACT FROM AUTHOR]

Objective: Our study aims to assess Ardisia japonica (AJ)'s anti-blood-stasis effect and its underlying action mechanisms. Methods: The primary components of AJ were determined using liquid chromatography–mass spectrometry (LC-MS). The blood stasis model was used to investigate the anti-blood-stasis effect of AJ extract. The underlying mechanisms of AJ against blood stasis were investigated via network pharmacology, molecular docking, and plasma non-targeted metabolomics. Results: In total, 94 compounds were identified from an aqueous extract of AJ, including terpenoids, phenylpropanoids, alkaloids, and fatty acyl compounds. In rats with blood stasis, AJ reduced the area of stasis, decreased the inflammatory reaction in the liver and lungs of rats, lowered the plasma viscosity, increased the index of erythrocyte deformability, and decreased the index of erythrocyte aggregation, suggesting that AJ has an anti-blood-stasis effect. Different metabolites were identified via plasma untargeted metabolomics, and it was found that AJ exerts its anti-blood-stasis effect by reducing inflammatory responses through the cysteine and methionine metabolism, linolenic acid metabolism, and sphingolipid metabolism. For the effect of AJ on blood stasis syndrome, the main active ingredients predicted via network pharmacology include sinensetin, galanin, isorhamnetin, kaempferol, wogonin, quercetin, and bergenin, and their targets were TP53, HSP90AA1, VEGFA, AKT1, EGFR, and PIK3CA that were mainly enriched in the PI3K/AKT and MAPK signaling pathways, which modulate the inflammatory response. Molecular docking was also performed, and the binding energies of these seven compounds to six proteins were less than −5, indicating that the chemical components bind to the target proteins. Conclusions: This study suggests AJ effectively prevents blood stasis by reducing inflammation. [ABSTRACT FROM AUTHOR]

The isolation of circulating tumor cells (CTCs) and their analysis are crucial for the preliminary identification of invasive cancer. One of the effective properties that can be utilized to isolate CTCs is their deformability. In this paper, inertial-based spiral microchannels with various numbers of loops are employed to sort deformable CTCs using the finite element method (FEM) and an arbitrary Lagrangian–Eulerian (ALE) approach. The influences of cell deformability, cell size, number of loops, and channel depth on the hydrodynamic behavior of CTCs are discussed. The results demonstrate that the trajectory of cells is affected by the above factors when passing through the spiral channel. This approach can be utilized for sorting and isolating label-free deformable biological cells at large scales in clinical systems. [ABSTRACT FROM AUTHOR]

Red blood cells (RBCs) are abundant (more than 80% of the total cells in the human body), yet relatively simple, as they lack nuclei and organelles, including mitochondria. Since the earliest days of biochemistry, the accessibility of blood and RBCs made them an ideal matrix for the characterization of metabolism. Because of this, investigations into RBC metabolism are of extreme relevance for research and diagnostic purposes in scientific and clinical endeavors. The relative simplicity of RBCs has made them an eligible model for the development of reconstruction maps of eukaryotic cell metabolism since the early days of systems biology. Computational models hold the potential to deepen knowledge of RBC metabolism, but also and foremost to predict in silico RBC metabolic behaviors in response to environmental stimuli. Here, we review now classic concepts on RBC metabolism, prior work in systems biology of unicellular organisms, and how this work paved the way for the development of reconstruction models of RBC metabolism. Translationally, we discuss how the fields of metabolomics and systems biology have generated evidence to advance our understanding of the RBC storage lesion, a process of decline in storage quality that impacts over a hundred million blood units transfused every year. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (CSVD) is a significant cause of cognitive impairment (CI), disability, and mortality. The insufficient effectiveness of antihypertensive therapy in curbing the disease justifies the search for potential targets for modifying therapy and indicators supporting its use. Using a laser-assisted optical rotational cell analyzer (LORRCA, Mechatronics, The Netherlands), the rheological properties and deformability of erythrocytes before and after incubation with 10 μmol/L of L-arginine, the nitric oxide (NO) donor, blood–brain barrier (BBB) permeability assessed by dynamic contrast-enhanced MRI, clinical, and MRI signs were studied in 73 patients with CSVD (48 women, mean age 60.1 ± 6.5 years). The control group consisted of 19 volunteers (14 women (73.7%), mean age 56.9 ± 6.4 years). The erythrocyte disaggregation rate (y-dis) after incubation with L-arginine showed better performance than other rheological characteristics in differentiating patients with reduced NO bioavailability/NO deficiency by its threshold values. Patients with y-dis > 113 s−1 had more severe CI, arterial hypertension, white matter lesions, and increased BBB permeability in grey matter and normal-appearing white matter (NAWM). A test to assess changes in the erythrocyte disaggregation rate after incubation with L-arginine can be used to identify patients with impaired NO bioavailability. L-arginine may be part of a therapeutic strategy for CSVD with CI. [ABSTRACT FROM AUTHOR]

We investigate some properties of exotic spherical configurations made of dark matter and dark energy. For the former, we adopt a polytropic equation-of-state, while for the latter, we adopt the extended Chaplygin gas equation-of-state. Solving the Tolman–Oppenheimer–Volkoff equations, within the two-fluid formalism, we compute the factor of compactness, the mass-to-radius relationships, as well as the tidal Love numbers and dimensionless deformabilities. A comparison between single-fluid objects and two-fluid configurations is made as well. [ABSTRACT FROM AUTHOR]

One of the most important breakthroughs in healthcare is the development of vaccines. The life cycle and its gene expression in the numerous virus-associated disorders must be considered when choosing the target vaccine antigen for Epstein–Barr virus (EBV). The vaccine candidate used in the current study will also be effective against all other herpesvirus strains, based on the conservancy study, which verified that the protein is present in all herpesviruses. From the screening, two B-cell epitopes, four MHC-I, and five MHC-II restricted epitopes were chosen for further study. The refined epitopes indicated 70.59% coverage of the population in Malaysia and 93.98% worldwide. After removing the one toxin (PADRE) from the original vaccine design, it was projected that the new vaccine would not be similar to the human host and would instead be antigenic, immunogenic, non-allergenic, and non-toxic. The vaccine construct was stable, thermostable, soluble, and hydrophilic. The immunological simulation projected that the vaccine candidate would be subject to a long-lasting active adaptive response and a short-lived active innate response. With IgM concentrations of up to 450 cells per mm3 and active B-cell concentrations of up to 400 cells per mm3, the B-cells remain active for a considerable time. The construct also discovered other conformational epitopes, improving its ability to stimulate an immune response. This suggests that, upon injection, the epitope will target the B-cell surface receptors and elicit a potent immune response. Furthermore, the discotope analysis confirmed that our conformational B-cell epitope was not displaced during the design. Lastly, the docking complex was stable and exhibited little deformability under heat pressure. These computational results are very encouraging for future testing of our proposed vaccine, which may potentially help in the management and prevention of EBV infections worldwide. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-related anemia is prevalent in up to 75% of patients, which may arise due to hemolysis and eryptosis. Alpha-mangostin (α-MG) is a polyphenolic xanthonoid found in the mangosteen tree (Garcinia mangostana) whose antitumor medicinal properties are well-established. Nevertheless, the potential toxic effects of α-MG on red blood cells (RBCs) have, as of yet, not been as well studied. Methods: RBCs were exposed to 1–40 μM of α-MG for 24 h at 37 °C. Hemolysis and related markers were measured using colorimetric assays, eryptotic cells were identified through Annexin-V-FITC, Ca2+ was detected with Fluo4/AM, and oxidative stress was assessed through H2DCFDA using flow cytometry. The toxicity of α-MG was also examined in the presence of specific signal transduction inhibitors and in whole blood. Results: α-MG at 10–40 μM caused dose-dependent hemolysis with concurrent significant elevation in K+, Mg2+, and LDH leakage, but at 2.5 μM it significantly increased the osmotic resistance of cells. A significant increase was also noted in Annexin-V-binding cells, along with intracellular Ca2+, oxidative stress, and cell shrinkage. Moreover, acetylcholinesterase activity was significantly inhibited by α-MG, whose hemolytic potential was significantly ameliorated by the presence of BAPTA-AM, vitamin C, NSC23766, and isosmotic sucrose but not urea. In whole blood, α-MG significantly depleted intracellular hemoglobin stores and was selectively toxic to platelets and monocytes. Conclusions: α-MG possesses hemolytic and eryptotic activities mediated through Ca2+ signaling, Rac1 GTPase activity, and oxidative injury. Also, α-MG leads to accelerated cellular aging and specifically targets platelet and monocyte populations in a whole blood milieu. [ABSTRACT FROM AUTHOR]

In 1995, Glendenning, Kettner and Weber postulated the existence of a new class of compact stars resembling white dwarfs but containing a small strange quark-matter core surrounded by hadronic layers attaining much higher densities than those found in white dwarfs. In our previous study, we have shown that it could be possible to unmask these so-called strange dwarfs through gravitational-wave observations with future space-based detectors such as the Laser Interferometer Space Antenna. We calculated more realistic equations of state for the hadronic envelope, but the quark core was treated using the simplest MIT bag model. In this paper, we investigate more closely the role of the possibly solid core in the structure and the tidal deformability of strange dwarfs in the full general relativistic framework by considering different models of strange quark matter in the crystalline color -superconducting phase. We find that the effect of the extreme rigidity of the elastic core on the tidal deformability is almost completely canceled by the surrounding hadronic layers. However, in all cases, the tidal deformability of strange dwarfs remains sufficiently lower than that of white dwarfs, to be potentially observable with gravitational waves despite the uncertainties in the strange quark-matter equation of state. [ABSTRACT FROM AUTHOR]

Cisplatin-induced acute kidney injury (AKI) is an important factor that limits the clinical use of this drug for the treatment of malignancies. Oxidative stress and inflammation are considered to be the main causes of not only cisplatin-induced death of cancer cells but also cisplatin-induced AKI. Therefore, developing agents that exert antioxidant and anti-inflammatory effects without weakening the anti-tumor effects of cisplatin is highly desirable. Carbon monoxide (CO) has recently attracted interest due to its antioxidant, anti-inflammatory, and anti-tumor properties. Herein, we report that CO-loaded red blood cell (CO-RBC) exerts renoprotective effects on cisplatin-induced AKI. Cisplatin treatment was found to reduce cell viability in proximal tubular cells via oxidative stress and inflammation. Cisplatin-induced cytotoxicity, however, was suppressed by the CO-RBC treatment. The intraperitoneal administration of cisplatin caused an elevation in the blood urea nitrogen and serum creatinine levels. The administration of CO-RBC significantly suppressed these elevations. Furthermore, the administration of CO-RBC also reduced the deterioration of renal histology and tubular cell injury through its antioxidant and anti-inflammatory effects in cisplatin-induced AKI mice. Thus, our data suggest that CO-RBC has the potential to substantially prevent the onset of cisplatin-induced AKI, which, in turn, may improve the usefulness of cisplatin-based chemotherapy. [ABSTRACT FROM AUTHOR]

Hepatic iron overload (HIO) is a hallmark of nonalcoholic fatty liver disease (NAFLD) with a poor prognosis. Recently, the role of hepatic erythrophagocytosis in NAFLD is emerging as a cause of HIO. We undertook various assays using human NAFLD patient pathology samples and an in vivo nonalcoholic steatohepatitis (NASH) mouse model named STAMTM. To make the in vitro conditions comparable to those of the in vivo NASH model, red blood cells (RBCs) and platelets were suspended and subjected to metabolic and inflammatory stresses. An insert-coculture system, in which activated THP-1 cells and RBCs are separated from HepG2 cells by a porous membrane, was also employed. Through various analyses in this study, the effect of cilostazol was examined. The NAFLD activity score, including steatosis, ballooning degeneration, inflammation, and fibrosis, was increased in STAMTM mice. Importantly, hemolysis occurred in the serum of STAMTM mice. Although cilostazol did not improve lipid or glucose profiles, it ameliorated hepatic steatosis and inflammation in STAMTM mice. Platelets (PLTs) played an important role in increasing erythrophagocytosis in the NASH liver. Upregulated erythrophagocytosis drives cells into ferroptosis, resulting in liver cell death. Cilostazol inhibited the augmentation of PLT and RBC accumulation. Cilostazol prevented the PLT-induced increase in ectopic erythrophagocytosis in in vivo and in vitro NASH models. Cilostazol attenuated ferroptosis of hepatocytes and phagocytosis of RBCs by THP-1 cells. Augmentation of hepatic erythrophagocytosis by activated platelets in NASH exacerbates HIO. Cilostazol prevents ectopic erythrophagocytosis, mitigating HIO-mediated ferroptosis in NASH models. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) deformability, expressing their ability to change their shape, allows them to minimize their resistance to flow and optimize oxygen delivery to the tissues. RBC with reduced deformability may lead to increased vascular resistance, capillary occlusion, and impaired perfusion and oxygen delivery. A reduction in deformability, as occurs during RBC physiological aging and under blood storage, is implicated in the pathophysiology of diverse conditions with circulatory disorders and anemias. The change in RBC deformability is associated with metabolic and structural alterations, mostly uncharacterized. To bridge this gap, we analyzed the membrane protein levels, using mass spectroscopy, of RBC with varying deformability determined by image analysis. In total, 752 membrane proteins were identified. However, deformability was positively correlated with the level of only fourteen proteins, with a highly significant inter-correlation between them. These proteins are involved in membrane rafting and/or the membrane–cytoskeleton linkage. These findings suggest that the reduction of deformability is a programmed (not arbitrary) process of remodeling and shedding of membrane fragments, possibly mirroring the formation of extracellular vesicles. The highly significant inter-correlation between the deformability-expressing proteins infers that the cell deformability can be assessed by determining the level of a few, possibly one, of them. [ABSTRACT FROM AUTHOR]

Blood image intensity has been used to detect erythrocyte sedimentation rate (ESR). However, it does not give information on the biophysical properties of blood samples under continuous ESR. In this study, to quantify mechanical variations of blood under continuous ESR, blood shear stress and blood image intensity were obtained by analyzing blood flows in the capillary channel. A blood sample is loaded into a driving syringe to demonstrate the proposed method. The blood flow rate is set in a periodic on–off pattern. A blood sample is then supplied into a capillary chip, and microscopic blood images are captured at specific intervals. Blood shear stress is quantified from the interface of the bloodstream in the coflowing channel. τ0 is defined as the maximum shear stress obtained at the first period. Simultaneously, ESRτ is then obtained by analyzing temporal variations of blood shear stress for every on period. AII is evaluated by analyzing the temporal variation of blood image intensity for every off period. According to the experimental results, a shorter period of T = 4 min and no air cavity contributes to the high sensitivity of the two indices (ESRτ and AII). The τ0 exhibits substantial differences with respect to hematocrits (i.e., 30–50%) as well as diluents. The ESRτ and AII showed a reciprocal relationship with each other. Three suggested properties represented substantial differences for suspended blood samples (i.e., hardened red blood cells, different concentrations of dextran solution, and fibrinogen). In conclusion, the present method can detect variations in blood samples under continuous ESR effectively. [ABSTRACT FROM AUTHOR]

The development of retinopathy of prematurity (ROP) may be influenced by anemia or a low fetal/adult hemoglobin ratio. We aimed to analyze the association between DNA methyltransferase 3 β (DNMT3B) (rs2424913), methylenetetrahydrofolate reductase (MTHFR) (rs1801133), and lysine-specific histone demethylase 1A (KDM1A) (rs7548692) polymorphisms, erythrocyte parameters during the first week of life, and ROP. In total, 396 infants (gestational age < 32 weeks or birth weight < 1500 g) were evaluated clinically and hematologically. Genotyping was performed using a MicroChip DNA on a platform employing iPlex MassARRAY®. Multivariate regression was performed after determining risk factors for ROP using univariate regression. In the group of infants who developed ROP red blood cell distribution width (RDW), erythroblasts, and mean corpuscular volume (MCV) were higher, while mean hemoglobin and mean corpuscular hemoglobin concentration (MCHC) were lower; higher RDW was associated with KDM1A (AA), MTHFR (CC and CC + TT), KDM1A (AA) + MTHFR (CC), and KDM1A (AA) + DNMT3B (allele C); KDM1A (AA) + MTHFR (CC) were associated with higher RDW, erythroblasts, MCV, and mean corpuscular hemoglobin (MCH); higher MCV and MCH were also associated with KDM1A (AA) + MTHFR (CC) + DNMT3B (allele C). We concluded that the polymorphisms studied may influence susceptibility to ROP by modulating erythropoiesis and gene expression of the fetal/adult hemoglobin ratio. [ABSTRACT FROM AUTHOR]

Simple Summary: We focused on changes in erythrocyte parameters—deformability, mean cell volume, and nitric oxide (NO) production by erythrocytes—in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, and on possible differences in these parameters as a function of age. We wanted to contribute to a more comprehensive understanding of the widely used animal model of essential hypertension—SHRs. We found that erythrocyte deformability was inversely proportional to the values of systolic blood pressure in normotensive animals, not in hypertensive ones. Regarding the relationship between the size of erythrocytes and blood pressure value, a significant negative correlation was found in SHRs, but not in WKY rats. In both normotensive and hypertensive animals, we observed a direct relationship between erythrocyte deformability and NO production by erythrocytes. Our study also suggests that age-related changes in erythrocyte deformability in both WKY and SHR are at least partially associated with changes in NO production. However, changes in NO production by erythrocytes in hypertension are probably not the primary factor affecting erythrocyte deformability. Summarizing the findings, the interpretation of the data obtained in erythrocyte parameters observed in SHRs to human hypertension needs precaution. Erythrocyte deformability, crucial for oxygen delivery to tissues, plays an important role in the etiology of various diseases. As the factor maintaining the erythrocyte deformability, nitric oxide (NO) has been identified. Reduced NO bioavailability also plays a role in the pathogenesis of hypertension. Our aim was to determine whether aging and hypertension affect erythrocyte deformability and NO production by erythrocytes in experimental animals divided into six groups according to age (7, 20 and 52 weeks), labeled WKY-7, WKY-20 and WKY-52 for normotensive Wistar-Kyoto (WKY) rats, and SHR-7, SHR-20 and SHR-52 for spontaneously hypertensive rats (SHR). The filtration method for the determination of erythrocyte deformability and the fluorescent probe DAF-2 DA for NO production were applied. Deformability and NO production by erythrocytes increased at a younger age, while a decrease in both parameters was observed at an older age. Strain-related differences in deformability were observed at 7 and 52 weeks of age. SHR-7 had reduced deformability and SHR-52 had increased deformability compared with age-matched WKY. Changes in NO production under hypertensive conditions are an unlikely primary factor affecting erythrocyte deformability, whereas age-related changes in deformability are at least partially associated with changes in NO production. However, an interpretation of data obtained in erythrocyte parameters observed in SHRs of human hypertension requires precaution. [ABSTRACT FROM AUTHOR]

(1) Background: We aimed to analyze the oxidative status of patients with unstable angina pectoris (UA), as well as to determine the correlation of these parameters between coronary arterial and peripheral venous blood samples. (2) Methods: The study included 47 human subjects with UA and 45 control subjects. We performed clinical examinations, hemodynamic and coronary angiography measures. Also, in the blood samples, we measured routine laboratory markers and the concentration of pro-oxidants: index of lipid peroxidation (TBARS), superoxide anion radical (O2−), hydrogen peroxide (H2O2) and nitrites (NO2−), while antioxidant parameters were determined from red blood cells: reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). All parameters were determined spectrophotometrically. (3) Results: Significantly higher values of TBARS and all measured antioxidants SOD, CAT and GSH were observed in the coronary arterial blood of the UA group relative to coronary arterial blood of the control subjects. On the other hand, in the peripheral venous blood samples, a significantly lower GSH value was found in the UA group compared to the control. (4) Conclusions: This study has shown that the majority of changes in all measured redox markers are found in coronary blood, especially related to the activity of antioxidant components. In patients with an unstable form of angina, prooxidants (superoxide anion radical and index of lipid peroxidation) and endogenous antioxidants (catalase, superoxide dismutase and reduced glutathione) are in direct correlation with the course of ischemic disease. Future studies, where participants would be randomized depending on symptom duration, are necessary to confirm these conclusions. [ABSTRACT FROM AUTHOR]

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs to perfectly integrate with the host's organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials as they exhibit good features in terms of impermeability, deformability, and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration; however, this kind of material lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these materials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields. In the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance, and patency is herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance is disclosed. [ABSTRACT FROM AUTHOR]

Red blood cells (RBC) are the most abundant cell in the human body, with a central role in oxygen transport and its delivery to tissues. However, omics technologies recently revealed the unanticipated complexity of the RBC proteome and metabolome, paving the way for a reinterpretation of the mechanisms by which RBC metabolism regulates systems biology beyond oxygen transport. The new data and analytical tools also informed the dissection of the changes that RBCs undergo during refrigerated storage under blood bank conditions, a logistic necessity that makes >100 million units available for life-saving transfusions every year worldwide. In this narrative review, we summarize the last decade of advances in the field of RBC metabolism in vivo and in the blood bank in vitro, a narrative largely influenced by the authors' own journeys in this field. We hope that this review will stimulate further research in this interesting and medically important area or, at least, serve as a testament to our fascination with this simple, yet complex, cell. [ABSTRACT FROM AUTHOR]

Their widespread presence throughout the vasculature, coupled with their reactivity, and thereby to their potential to release reactive oxidative species, or to utilize their anti-oxidative capacities, has promoted much discussion of the role(s) of red blood cells (RBCs) in the progression of health or, alternatively, a wide range of disease states. Moreover, these role(s) have been linked to the development of adhesiveness and, in fact, thereby to the essential pathway to their eventual clearance, e.g., by macrophages in the spleen. These disparate roles coupled with the mechanisms involved are reviewed and given. Following an analysis, novel perspectives are provided; these perspectives can lead to novel assays for identifying the potential for RBC adhesiveness as suggested herein. We describe this paradigm, that involves RBC adhesiveness, hemolysis, and ghost formation, with examples including, inter alia, the progression of atherosclerosis and the suppression of tumor growth along with other disease states. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) transfusion is a lifesaving medical procedure that can treat patients with anemia and hemoglobin disorders. However, the shortage of blood supply and risks of transfusion-transmitted infection and immune incompatibility present a challenge for transfusion. The in vitro generation of RBCs or erythrocytes holds great promise for transfusion medicine and novel cell-based therapies. While hematopoietic stem cells and progenitors derived from peripheral blood, cord blood, and bone marrow can give rise to erythrocytes, the use of human pluripotent stem cells (hPSCs) has also provided an important opportunity to obtain erythrocytes. These hPSCs include both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). As hESCs carry ethical and political controversies, hiPSCs can be a more universal source for RBC generation. In this review, we first discuss the key concepts and mechanisms of erythropoiesis. Thereafter, we summarize different methodologies to differentiate hPSCs into erythrocytes with an emphasis on the key features of human definitive erythroid lineage cells. Finally, we address the current limitations and future directions of clinical applications using hiPSC-derived erythrocytes. [ABSTRACT FROM AUTHOR]

Blood flow in the microcirculatory system is crucially affected by intrinsic red blood cell (RBC) properties, such as their deformability. In the smallest vessels of this network, RBCs adapt their shapes to the flow conditions. Although it is known that the age of RBCs modifies their physical properties, such as increased cytosol viscosity and altered viscoelastic membrane properties, the evolution of their shape-adapting abilities during senescence remains unclear. In this study, we investigated the effect of RBC properties on the microcapillary in vitro flow behavior and their characteristic shapes in microfluidic channels. For this, we fractioned RBCs from healthy donors according to their age. Moreover, the membranes of fresh RBCs were chemically rigidified using diamide to study the effect of isolated graded-membrane rigidity. Our results show that a fraction of stable, asymmetric, off-centered slipper-like cells at high velocities decreases with increasing age or diamide concentration. However, while old cells form an enhanced number of stable symmetric croissants at the channel centerline, this shape class is suppressed for purely rigidified cells with diamide. Our study provides further knowledge about the distinct effects of age-related changes of intrinsic cell properties on the single-cell flow behavior of RBCs in confined flows due to inter-cellular age-related cell heterogeneity. [ABSTRACT FROM AUTHOR]

This work presents a dataset comprising images, annotations, and velocity fields for benchmarking cell detection and cell tracking algorithms. The dataset includes two video sequences captured during laboratory experiments, showcasing the flow of red blood cells (RBC) in microfluidic channels. From the first video 300 frames and from the second video 150 frames are annotated with bounding boxes around the cells, as well as tracks depicting the movement of individual cells throughout the video. The dataset encompasses approximately 20,000 bounding boxes and 350 tracks. Additionally, computational fluid dynamics simulations were utilized to generate 2D velocity fields representing the flow within the channels. These velocity fields are included in the dataset. The velocity field has been employed to improve cell tracking by predicting the positions of cells across frames. The paper also provides a comprehensive discussion on the utilization of the flow matrix in the tracking steps. [ABSTRACT FROM AUTHOR]

Strange stars ought to exist in the universe according to the strange quark matter hypothesis, which states that matter made of roughly equal numbers of up, down, and strange quarks could be the true ground state of baryonic matter rather than ordinary atomic nuclei. Theoretical models of strange quark matter, such as the standard MIT bag model, the density-dependent quark mass model, or the quasi-particle model, however, appear to be unable to reproduce some of the properties (masses, radii, and tidal deformabilities) of recently observed compact stars. This is different if alternative gravity theory (e.g., non-Newtonian gravity) or dark matter (e.g., mirror dark matter) are considered, which resolve these issues. The possible existence of strange stars could thus provide a clue to new physics, as discussed in this review. [ABSTRACT FROM AUTHOR]

Erythrocyte enrichment is needed for blood disease diagnosis and research. DLD arrays with an I-shaped pillar (I-pillar) sort erythrocytes in a unique, accurate, and low-reagent method. However, the existing I-shaped pillar DLD arrays for erythrocyte sorting have the drawbacks of higher flow resistance and more challenging fabrication. A two-dimensional erythrocyte simulation model and the arbitrary Lagrangian–Euler equations at the cell–fluid boundary were built based on the fluid–solid coupling method to investigate the influencing factors of the erythrocyte flow path in an I-pillar DLD array and find its optimization method. Three different sizes of I-pillars were built and multiple sets of corresponding arrays were constructed, followed by finite element simulations to separately investigate the effects of these arrays on the induction of erythrocyte motion paths. This work demonstrates the motion paths of erythrocyte models in a series of I-pillar arrays with different design parameters, aiming to summarize the variation modes of erythrocyte motion paths, which in turn provides some reference for designing and optimizing the pillar size and array arrangement methods for I-pillar array DLD chips. [ABSTRACT FROM AUTHOR]

UV radiation (UVR) is responsible for inducing both harmful and beneficial effects on skin health. Specifically, it has been reported to disrupt oxidant and antioxidant levels, leading to oxidative stress conditions in skin tissue. This phenomenon might trigger photo-carcinogenesis, resulting in melanoma, NMSC (non-melanoma skin cancer), such as BCC (basal cell carcinoma) and SCC (squamous cell carcinoma), and actinic keratosis. On the other hand, UVR is essential for the production of adequate vitamin D levels, a hormone with important antioxidant, anticancer and immunomodulatory properties. The exact mechanisms implicated in this two-fold action are not well understood, as there still no clear relation established between skin cancer and vitamin D status. Oxidative stress seems to be a neglected aspect of this complex relation, despite its role in both skin cancer development and vitamin D deficiency. Therefore, the aim of the present study is to examine the correlation between vitamin D and oxidative stress in skin cancer patients. A total of 100 subjects (25 with SCC, 26 with BCC, 23 with actinic keratosis, and 27 controls) were assessed in terms of 25-hydroxyvitamin D (25(OH) D) and redox markers such as thiobarbituric acid reactive substances (TBARS), protein carbonyls, total antioxidant capacity (TAC) in plasma, glutathione (GSH) levels and catalase activity in erythrocytes. The majority of our patients revealed low vitamin D levels; 37% of the subjects showed deficiency (<20 ng/mL) and 35% insufficiency (21–29 ng/mL). The mean 25(OH) D level of the NMSC patients (20.87 ng/mL) was also found to be significantly lower (p = 0.004) than that of the non-cancer patients (28.14 ng/mL). Furthermore, higher vitamin D levels were also correlated with lower oxidative stress (positive correlation with GSH, catalase activity TAC index and negative correlation with TBARS and CARBS indices). NMSC patients diagnosed with SCC showed lower catalase activity values compared to non-cancer patients (p < 0.001), with the lowest values occurring in patients with a chronic cancer diagnosis (p < 0.001) and vitamin D deficiency (p < 0.001). Higher GSH levels (p = 0.001) and lower TBARS levels (p = 0.016) were found in the control group compared to the NMSC group, and to patients with actinic keratosis. Higher levels of CARBS were observed in patients with SCC (p < 0.001). Non-cancer patients with vitamin D sufficiency showed higher TAC values compared to non-cancer patients with vitamin D deficiency (p = 0.023) and to NMSC patients (p = 0.036). The above-mentioned results indicate that NMSC patients reveal increased levels of oxidative damage markers compared to control levels, while vitamin D status plays a critical role in the determination of individuals' oxidative status. [ABSTRACT FROM AUTHOR]

Background: Physical activity at high-altitudes is increasingly widespread, both for tourist trekking and for the growing tendency to carry out sports and training activities at high-altitudes. Acute exposure to this hypobaric–hypoxic condition induces several complex adaptive mechanisms involving the cardiovascular, respiratory and endocrine systems. A lack of these adaptive mechanisms in microcirculation may cause the onset of symptoms of acute mountain sickness, a frequent disturbance after acute exposure at high altitudes. The aim of our study was to evaluate the microcirculatory adaptive mechanisms at different altitudes, from 1350 to 5050 m a.s.l., during a scientific expedition in the Himalayas. Methods: The main haematological parameters, blood viscosity and erythrocyte deformability were assessed at different altitudes on eight European lowlanders and on a group of eleven Nepalese highlanders. The microcirculation network was evaluated in vivo by conjunctival and periungual biomicroscopy. Results: Europeans showed a progressive and significant reduction of blood filterability and an increase of whole blood viscosity which correlate with the increase of altitude (p < 0.02). In the Nepalese highlanders, haemorheological changes were already present at their residence altitude, 3400 m a.s.l. (p < 0.001 vs. Europeans). With the increase in altitude, a massive interstitial oedema appeared in all participants, associated with erythrocyte aggregation phenomena and slowing of the flow rate in the microcirculation. Conclusions: High altitude causes important and significant microcirculatory adaptations. These changes in microcirculation induced by hypobaric–hypoxic conditions should be considered when planning training and physical activity at altitude. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) presents with maternal de novo hypertension and significant proteinuria and is one of the leading causes of maternal and perinatal morbidity and mortality with unknown etiology. The disease is associated with inflammatory vascular response and severe red blood cell (RBC) morphology changes. This study examined the nanoscopic morphological changes of RBCs from PE women versus normotensive healthy pregnant controls (PCs) and non-pregnant controls (NPCs) applying atomic force microscopy (AFM) imaging. The results revealed that the membrane of fresh PE RBCs differed significantly from healthy ones by the presence of invaginations and protrusions and an increased roughness value (Rrms) (4.7 ± 0.8 nm for PE vs. 3.8 ± 0.5 nm and 2.9 ± 0.4 nm for PCs and NPCs, respectively). PE-cells aging resulted in more pronounced protrusions and concavities, with exponentially increasing Rrms values, in contrast to the controls, where the Rrms parameter decreased linearly with time. The Rrms, evaluated on a 2 × 2 µm2 scanned area, for senescent PE cells (13 ± 2.0 nm) was significantly higher (p < 0.01) than that of PCs (1.5 ± 0.2 nm) and NPCs (1.9 ± 0.2 nm). Furthermore, the RBCs from PE patients appeared fragile, and often only ghosts were observed instead of intact cells at 20–30 days of aging. Oxidative-stress simulation on healthy cells led to RBC membrane features similar to those observed for PE cells. The results demonstrate that the most pronounced effects on RBCs in PE patients are related to impaired membrane homogeneity and strongly altered roughness values, as well as to vesiculation and ghost formation in the course of cell aging. [ABSTRACT FROM AUTHOR]

Crystalline metals generally exhibit good deformability but low strength and poor irradiation tolerance. Amorphous materials in general display poor deformability but high strength and good irradiation tolerance. Interestingly, refining characteristic size can enhance the flow strength of crystalline metals and the deformability of amorphous materials. Thus, crystalline–amorphous nanostructures can exhibit an enhanced strength and an improved plastic flow stability. In addition, high-density interfaces can trap radiation-induced defects and accommodate free volume fluctuation. In this article, we review crystalline–amorphous nanocomposites with characteristic microstructures including nanolaminates, core–shell microstructures, and crystalline/amorphous-based dual-phase nanocomposites. The focus is put on synthesis of characteristic microstructures, deformation behaviors, and multiscale materials modelling. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are tumor cells shed from the primary tumor into circulation, with clusters of CTCs responsible for cancer metastases. CTC detection and isolation from the bloodstream are based on properties distinguishing CTCs from normal blood cells. Current CTC detection techniques can be divided into two main categories: label dependent, which depends upon antibodies that selectively bind cell surface antigens present on CTCs, or label-independent detection, which is detection based on the size, deformability, and biophysical properties of CTCs. CTCs may play significant roles in cancer screening, diagnosis, treatment navigation, including prognostication and precision medicine, and surveillance. In cancer screening, capturing and evaluating CTCs from peripheral blood could be a strategy to detect cancer at its earliest stage. Cancer diagnosis using liquid biopsy could also have tremendous benefits. Full utilization of CTCs in the clinical management of malignancies may be feasible in the near future; however, several challenges still exist. CTC assays currently lack adequate sensitivity, especially in early-stage solid malignancies, due to low numbers of detectable CTCs. As assays improve and more trials evaluate the clinical utility of CTC detection in guiding therapies, we anticipate increased use in cancer management. [ABSTRACT FROM AUTHOR]

Methemoglobinemia is an acquired or inherited condition resulting from oxidative stress or dysfunction of the NADH-cytochrome b5 reductase or associated pathways. This study describes the clinical, pathophysiological, and molecular genetic features of a cat with hereditary methemoglobinemia. Whole genome sequencing and mRNA transcript analyses were performed in affected and control cats. Co-oximetry, ektacytometry, Ellman's assay for reduced glutathione concentrations, and CYB5R activity were assessed. A young adult European domestic shorthair cat decompensated at induction of anesthesia and was found to have persistent methemoglobinemia of 39 ± 8% (reference range < 3%) of total hemoglobin which could be reversed upon intravenous methylene blue injection. The erythrocytic CYB5R activity was 20 ± 6% of normal. Genetic analyses revealed a single homozygous base exchange at the beginning of intron 3 of the CYB5R3 gene, c.226+5G>A. Subsequent mRNA studies confirmed a splice defect and demonstrated expression of two mutant CYB5R3 transcripts. Erythrocytic glutathione levels were twice that of controls. Mild microcytosis, echinocytes, and multiple Ca2+-filled vesicles were found in the affected cat. Erythrocytes were unstable at high osmolarities although highly deformable as follows from the changes in elongation index and maximal-tolerated osmolarity. Clinicopathological presentation of this cat was similar to other cats with CYB5R3 deficiency. We found that methemoglobinemia is associated with an increase in red blood cell fragility and deformability, glutathione overload, and morphological alterations typical for stress erythropoiesis. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) deformability is the ability of cells to modulate their shape to ensure transit through narrow capillaries of the microcirculation. A loss of deformability can occur in several pathological conditions, during natural RBC aging through an increase in membrane protein phosphorylation, and/or through the structural rearrangements of cytoskeletal proteins due to oxidative conditions, with a key role played by band 3. Due to the close relationship between aging and oxidative stress, flavonoid-rich foods are good candidates to counteract age-related alterations. This study aims to verify the beneficial role of Açaì extract in a d-Galactose (d-Gal)-induced model of aging in human RBCs. To this end, band 3 phosphorylation and structural rearrangements in membrane cytoskeleton-associated proteins, namely spectrin, ankyrin, and/or protein 4.1, are analyzed in RBCs treated with 100 mM d-Gal for 24 h, with or without pre-incubation with 10 μg/mL Açaì extract for 1 h. Furthermore, RBC deformability is also measured. Tyrosine phosphorylation of band 3, membrane cytoskeleton-associated proteins, and RBC deformability (elongation index) are analyzed using western blotting analysis, FACScan flow cytometry, and ektacytometry, respectively. The present data show that: (i) Açaì berry extract restores the increase in band 3 tyrosine phosphorylation and Syk kinase levels after exposure to 100 mM d-Gal treatment; and (ii) Açaì berry extract partially restores alterations in the distribution of spectrin, ankyrin, and protein 4.1. Interestingly, the significant decrease in membrane RBC deformability associated with d-Gal treatment is alleviated by pre-treatment with Açaì extract. These findings further contribute to clarify mechanisms of natural aging in human RBCs, and propose flavonoid substances as potential natural antioxidants for the treatment and/or prevention of oxidative-stress-related disease risk. [ABSTRACT FROM AUTHOR]