Red Blood Cell Damage Research Articles

WITHDRAWN: Exploration of the mechanism of reinfusion of fresh autologous blood in type 2 diabetic body to induce macrophage polarization and inhibit erythrocyte damage

BackgroundType 2 diabetes (T2D) triggers an inflammatory response that can damage red blood cells. M2 macrophages have inhibitory effects on inflammation and play an important role in tissue damage repair and fibrosis. Autologous blood transfusion has the potential to inhibit red blood cell damage by mediating macrophage polarization. MethodsSwiss mice were used to establish a suitable type 2 diabetes model and autologous blood transfusion was performed. The mice were executed, the blood of the mice was collected, and CD14+ monocytes were sorted. The expression levels of phenotypic molecules CD16, CD32 and CD206 in CD14+ monocytes were analyzed by flow cytometry. The proportion of M1 and M2 macrophages were analyzed by flow cytometry. The Q value, P50, 2,3-DPG and Na+-K+-ATPase of red blood cells were detected. The red blood cell osmotic fragility test analyzed the RBC osmotic fragility. Western Blot analysis was used to analyze the expression changes of erythrocyte surface membrane proteins or transporters EPB41, S1P, GLTP and SPPL2A. ResultsAutologous blood transfusion induced a significant increase in the number of macrophages. The state and capacity of blood cells improved with autologous blood transfusion. Reinfusion of fresh autologous blood in T2D body made erythrocytes shrank. The expression of erythrocyte-related proteins proved that the erythrocyte injury in the Fresh+T2D group was significantly reduced. ConclusionThe reinfusion of fresh autologous blood into the body of patients with type 2 diabetes can induce macrophage polarization to M2, thereby inhibiting red blood cell damage.

Oxidative Stress in Healthy and Pathological Red Blood Cells.

Red cell diseases encompass a group of inherited or acquired erythrocyte disorders that affect the structure, function, or production of red blood cells (RBCs). These disorders can lead to various clinical manifestations, including anemia, hemolysis, inflammation, and impaired oxygen-carrying capacity. Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense mechanisms, plays a significant role in the pathophysiology of red cell diseases. In this review, we discuss the most relevant oxidant species involved in RBC damage, the enzymatic and low molecular weight antioxidant systems that protect RBCs against oxidative injury, and finally, the role of oxidative stress in different red cell diseases, including sickle cell disease, glucose 6-phosphate dehydrogenase deficiency, and pyruvate kinase deficiency, highlighting the underlying mechanisms leading to pathological RBC phenotypes.

Radio-mitigation properties of α-lipoic acid when used alone and in combination with metformin or ethylmethylhydroxypyridine succinate (mexidol) in mice after exposure to X-ray radiation

This study explored the radio-mitigation properties of α-lipoic acid and combination of α-lipoic acid with metformin and mexidol in animals during the process of X-ray irradiation. The results of the micronucleus test for measuring radiation-induced DNA damage of polychromatophilic red blood cells in the bone marrow of mice showed that α-lipoic acid has gene-protective and radio-mitigation properties in vivo. A study on the survival rate of the lethal dose-irradiated mice within 30 days confirmed that α-lipoic acid has radio-mitigation properties. The radio-mitigation effect of α-lipoic acid is dose-dependent, the effect increases with decreasing dose. α-lipoic acid in combination with mexidol and metformin exhibited a weaker radio-mitigation effect.

Association between Glyphosate Exposure and Erythrograms in a Representative Sample of US Adults: NHANES 2013-2014.

Glyphosate is the most commonly utilized herbicide globally, and a growing body of experimental research has linked its exposure to red blood cell damage. However, the potential toxicity of glyphosate exposure on erythrocytes in the general population remains poorly understood. Therefore, we analyzed data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) of 1466 adults (≥ 18years) to explore the potential relationship between glyphosate exposure and erythrocyte profiles. Our results indicated a significant negative association between urinary glyphosate levels and hemoglobin (Hb) and hematocrit (Hct) in multiple regression analysis, with ß coefficients of -0.157 (S.E. = 0.055, P = 0.012) and -0.431 (S.E. = 0.195, P = 0.043), respectively. Additionally, the odds ratio showed a significant increase in individuals with anemia with a one-unit increase in ln-glyphosate levels (odds ratio = 1.523 (95% CI = 1.301 - 1.783), P < 0.001 in the final model). The negative correlation between glyphosate and Hb was more pronounced in subjects older than 60years, non-Hispanic white ethnicity, lower income, and those with a body mass index (BMI) < 25 and ≥ 30. In conclusion, our results provide preliminary evidence of a plausible association between glyphosate exposure and anemia in a subset of the adult population in the United States. However, further research is necessary to understand the underlying mechanisms and clinical implications of this association.

In vitro comparative study of red blood cell and VWF damage on 3D printing biomaterials under different blood-contacting conditions.

Mechanical circulatory support devices (MCSDs) are often associated with hemocompatible complications such as hemolysis and gastrointestinal bleeding when treating patients with end-stage heart failure. Shear stress and exposure time have been identified as the two most important mechanical factors causing blood damage. However, the materials of MCSDs may also induce blood damage when contacting with blood. In this study, the red blood cell and von Willebrand Factor (VWF) damage caused by four 3D printing biomaterials were investigated, including acrylic, PCISO, Somos EvoLVe 128, and stainless steel. A roller pump circulation experimental platform and a rotor blood-shearing experimental platform were constructed to mimic static and dynamic blood-contacting conditions of materials in MCSDs, respectively. Free hemoglobin assay and VWF molecular weight analysis were performed on the experimental blood samples. It indicated that different 3D printing materials and technology could induce different levels of damage to red blood cells and VWF, with acrylic causing the least damage under both static and dynamic conditions. In addition, it was found that blood damage measured for the same material differed on the two platforms. Therefore, a combination of static and dynamic experiments should be used to comprehensively investigate the effects of blood damage caused by the material. It can provide a reference for the design and evaluation of materials in different components of MCSDs.

New Insights into Immunopathology Associated to Bothrops lanceolatus Snake Envenomation: Focus on PLA2 Toxin.

The systemic increase in inflammatory mediator levels can induce diverse pathological disorders, including potentially thrombus formation, which may be lethal. Among the clinical conditions in which the formation of thrombi dictates the patient's prognosis, envenomation by Bothrops lanceolatus should be emphasized, as it can evolve to stroke, myocardial infarction and pulmonary embolism. Despite their life-threatening potential, the immunopathological events and toxins involved in these reactions remain poorly explored. Therefore, in the present study, we examined the immunopathological events triggered by a PLA2 purified from B. lanceolatus venom, using an ex vivo human blood model of inflammation. Our results showed that the purified PLA2 from the venom of B. lanceolatus damages human erythrocytes in a dose dependent way. The cell injury was associated with a decrease in the levels of CD55 and CD59 complement regulators on the cell surface. Moreover, the generation of anaphylatoxins (C3a and C5a) and the soluble terminal complement complex (sTCC) indicates that human blood exposure to the toxin activates the complement system. Increased production of TNF-α, CXCL8, CCL2 and CCL5 followed complement activation. The venom PLA2 also triggered the generation of lipid mediators, as evidenced by the detected high levels of LTB4, PGE2 and TXB2. The scenario here observed of red blood cell damage, dysfunctions of the complement regulatory proteins, accompanied by an inflammatory mediator storm, suggests that B. lanceolatus venom PLA2 contributes to the thrombotic disorders present in the envenomed individuals.

Comparision of Exercise Induced Alteration of Hematological Profile in Sedentary Post Pubertal Boys and Girls

Background: Moderate intensified exercise causes leukocytosis due to increased trafficking of white blood cellsand also causes red blood cells damage (RBC) and hemolysis due to osmotic and mechanical stress.Aim: This study was aimed to investigate the exercise induced changes in the haematological profile in sedentarypost pubertal boys and girlsMethodology: 40 participants (20boys, 20 girls) with sedentary behaviour in the age group of 16 to 25 wereselected from outpatient department of Thanjavur Medical College, for this study. Participants were asked to runin treadmill at the speed of 3km per hour at 0% elevations for few minutes then progressive incremental treadmillrunning with change in speed 1km per hour and elevations(1%) alternatively after each 2 mins for 20 mins.Informed consent was taken from the participants.This study was approved by human ethics Committee Thanjavur Medical College, Thanjavur.Blood samples collected from sedentary post pubertal boys and girls before and immediately after exercise to assessthe hematological variation in Hemoglobin (Hb), White blood cells (wbc), Red blood cells (Rbc) and differentialcount, and the results were statistically analysed using paired t –test.Results: Post exercise Hb was significantly higher in post pubertal girls (10.69±1.20 g%) as compared to boys(12.3±1.94 g%); p=0.029, p≤0.05. Also post exercise RBC showed significance with p value of 0.016 (p≤0.05) ingirls (4.20 ± 0.47 million/cumm) as compared to boys (4.67 ±0.70 million/cumm, p=0.261, p≥0.05). Leukocytecount, lymphocyte, neutrophil increased significantly in both groups following exercise. Eosinophils increasedsignificantly in girls (3.20±1.15(%), (p=0.024, p≤0.05)) as compared to boys (3.20±0.95(%), (p=0.886, p≥0.05).Conclusion: We conclude that post exercise Hb, RBC, Eosinophil showed significant rise in females as compared tomales. Leukocytes, neutrophils and lymphocytes showed significance in both genders. Genders have insignificantimpact on exercise induced alteration of hematological profile except Hb, RBC and Eosinophils.

Concerted phenotypic flexibility of avian erythrocyte size and number in response to dietary anthocyanin supplementation

BackgroundEndurance flight impose substantial oxidative costs on the avian oxygen delivery system. In particular, the accumulation of irreversible damage in red blood cells can reduce the capacity of blood to transport oxygen and limit aerobic performance. Many songbirds consume large amounts of anthocyanin-rich fruit, which is hypothesized to reduce oxidative costs, enhance post-flight regeneration, and enable greater aerobic capacity. While their antioxidant benefits appear most straightforward, the effects of anthocyanins on blood composition remain so far unknown. We fed thirty hand-raised European starlings (Sturnus vulgaris) two semisynthetic diets (with or without anthocyanin supplement) and manipulated the extent of flight activity in a wind tunnel (daily flying or non-flying for over two weeks) to test for their interactive effects on functionally important haematological variables.ResultsSupplemented birds had on average 15% more and 4% smaller red blood cells compared to non-supplemented individuals and these diet effects were independent of flight manipulation. Haemoglobin content was 7% higher in non-supplemented flying birds compared to non-flying birds, while similar haemoglobin content was observed among supplemented birds that were flown or not. Neither diet nor flight activity influenced haematocrit.ConclusionThe concerted adjustments suggest that supplementation generally improved antioxidant protection in blood, which could prevent the excess removal of cells from the bloodstream and may have several implications on the oxygen delivery system, including improved gas exchange and blood flow. The flexible haematological response to dietary anthocyanins may also suggest that free-ranging species preferentially consume anthocyanin-rich fruits for their natural blood doping, oxygen delivery-enhancement effects.

Entropy analysis on the bioconvective peristaltic flow of gyrotactic microbes in Eyring-Powell nanofluid through an asymmetric channel

The educational value of nanofluids in several industrial and biological sectors, particularly in fluid movement systems known as peristalsis, has piqued researchers' interest in studying the peristaltic movement of nanofluids. Additionally, nanoparticles have crucial roles in many engineering and manufacturing processes, including those involving heat exchangers, cooling systems, boilers, MEMS, chemical engineering, laser diode arrays, and cool automotive engines. Various studies have been conducted on this subject. This is done by looking at how migratory gyrotactic microorganisms migrate through an artery that is anisotropically narrowing in a blood-based nanofluid that is non-Newtonian. To comprehend, the Powell-Eyring fluid model is used how the blood's rheology differs from that of a Newtonian fluid. Both Newtonian fluid characteristics and non-Newtonian traits can be seen in this fluid pattern. Equations for continuity, temperature, motile microbes, momentum, and concentration are used to create the mathematical formulation. The series solutions, which are produced using perturbation theory solutions are discussed using graphs for all dominant parameters. Discussion also includes the distribution of temperature, velocity, and swimming microorganisms. Additionally, the effects of wall shear stress, the Nusselt and Sherwood numbers, as well as the phenomena of trapping, are all examined in detail and shown in the graphs. Entropy generation analyses have also been undertaken. The investigation also reveals a crucial behaviour in the use of the heart-lung engine for extracorporeal blood circulation in medicine that may have an impact on the damage of red blood cells as a result of the large fluctuation in wall shear stress. When liquids are transported using arthro pumps and roller pumps in living organs, the results are likewise of significant use. The results are very helpful for executing particle movements in cardiac surgery and may be applicable to the fluid peristaltic pump used in haemodialysis.

Arginine attenuates chronic mountain sickness in rats via microRNA-144-5p.

Hypobaric hypoxia is an environmental stress leading to high-altitude pulmonary hypertension. While high-altitude pulmonary hypertension has been linked to high hematocrit findings (chronic mountain sickness; CMS). The present study is designed to investigate the effect of arginine (ARG) on hypobaric hypoxia-induced CMS of rats. Hypobaric hypoxia resulted in lower body weight, decreased appetite, increased pulmonary artery pressure, and deteriorated lung tissue damage in rats. Red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin values and blood viscosity were increased in rats, which were alleviated by ARG. microRNA (miRNA) microarray analysis was used to filter differentially expressed miRNAs after ARG in rats. miR-144-5p was reduced under hypobaric hypoxia and upregulated by ARG. miR-144-5p silencing aggravated the erythrocytosis and hyperviscosity in rats, and also accentuated tissue damage and excessive accumulation of RBC. The role of miR-144-5p in rats with CMS was achieved by blocking erythropoietin (EPO)/erythropoietin receptor (EPOR). In conclusion, ARG alleviated CMS symptoms in rodents exposed to hypobaric hypoxia by decreasing EPO/EPOR via miR-144-5p.

Chemical Profile and Hematoprotective Activity of Artisanal Jabuticaba (Plinia jabuticaba) Wine and Derived Extracts

The alcoholic fermentation of jabuticaba berries (Plinia spp.) originates from a beverage with an intense taste and aroma, popularly known as jabuticaba wine (JW). In addition, polyphenols transferred from fruit peels to the final product turn this beverage into a promising source of bioactive agents. Here, the chemical profile and antioxidant potential of artisanal JW and derivative extracts were determined. Volatile organic compounds were determined by HS-SPME/GC-MS analysis. The wine was dried by lyophilization and subjected to liquid-liquid partitioning (water: ethyl acetate), resulting in three fractions (JWF1-3). ABTS•+ and DPPH•+ scavenging assays were performed to evaluate the antioxidant capacity. In addition, the extracts’ hematoprotective activity was evaluated against oxidative stress. Finally, the extracts were analyzed by LC-HRMS/MS. HS-SPME/GC-MS analysis highlighted 1,8-cineole as the main compound that contributes to the camphor/mint flavor. JWF2 and JWF3 displayed the highest antioxidant capacity. JWF2 stood out for preventing oxidative damage in red blood cells at 7.8 µg·mL−1 The maximal protection of ascorbic acid occurred at 8.8 µg·mL−1. The LC-HRMS/MS analysis allowed the annotation of seventeen compounds, most of them with recognized antioxidant activity such as anthocyanins, catechins, flavanols, and phenolic acids. The results presented herein reinforce JW as a pleasant beverage with bioactive potential.

Lamprey Wound Healing and Regenerative Effects: The Collaborative Efforts of Diverse Drivers

Skin is a natural barrier between the body and the external environment, and this important multifunctional organ plays roles in body temperature regulation, sensory stimulation, mucus secretion, metabolite excretion and immune defense. Lampreys, as ancient vertebrates, rarely experience infection of damaged skin during farming and efficiently promote skin wound healing. However, the mechanism underlying these wound healing and regenerative effects is unclear. Our histology and transcriptomics results demonstrate that lampreys regenerate a nearly complete skin structure in damaged epidermis, including the secretory glands, and will almost not be infected, even if experiencing full-thickness damage. In addition, ATGL, DGL and MGL participate in the lipolysis process to provide space for infiltrating cells. A large number of red blood cells migrate to the site of injury and exert proinflammatory effects, upregulating the expression of proinflammatory factors such as IL-8 and IL-17. Based on a lamprey skin damage healing model, adipocytes and red blood cells in the subcutaneous fat layer can promote wound healing, which provides a new approach for the study of skin healing mechanisms. Transcriptome data reveal that mechanical signal transduction pathways are mainly regulated by focal adhesion kinase and that the actin cytoskeleton plays an important role in the healing of lamprey skin injuries. We identified RAC1 as a key regulatory gene that is necessary and partially sufficient for wound regeneration. Insights into the mechanisms of lamprey skin injury and healing will provide a theoretical basis for overcoming the challenges associated with chronic healing and scar healing in the clinic.

Hemolysis prediction in bio-microfluidic applications using resolved CFD-DEM simulations

Background and ObjectiveHemolysis, namely hemoglobin leakage from red blood cells (RBCs), is one of the major sources of incorrect results in clinical tests, especially when passive microfluidics is involved. This is due to small characteristic dimensions which could cause strong RBCs deformation. Prediction of hemolysis is essential in the design and optimization of lab-on-a-chip devices for cell sorting and plasma separation. The aim of this work is to provide a numerical simulation tool this purpose applicable to real-scale bio-microfluidic devices with affordable computational cost. MethodsBlood is modelled as a suspension of biological cells, mainly RBCs, in liquid plasma assumed as a Newtonian, incompressible carrier fluid. Therefore, the physics of cells and carrier fluid is coupled by means of an immersed boundary concept known as resolved CFD-DEM. In this approach, the Navier-Stokes equations are numerically solved through a finite volume method with an additional penalty term to account for the presence of RBCs. RBCs’ positions and velocities are updated by solving Newton and Euler equations for conservation of linear and angular momentum. To model the RBCs deformation, a reduced-order model is employed, where each RBC is represented by a clump of overlapping rigid spheres connected by fictional numerical bonds, whose properties are tuned to reproduce the ones of RBCs viscoelastic membrane. This coupled approach allows access to cell-level information and facilitates the usage of strain-based hemolysis models. ResultsDifferent micro-channel geometries and blood hematocrits are simulated, to explore the influence of these factors on RBCs damage. Statistical analysis is performed to extract relevant biophysical quantities from numerical simulations such as hemolysis index distribution at the channel exit. Finally, the effect of carrier fluid viscosity is studied in relation to cell-cell interactions. ConclusionsSimulation results show that hemolysis occurrence is almost independent of the hematocrit values in the microchannel, implying the possibility to speed up calculation using low hematocrit values. Nevertheless, using whole blood viscosity for the carrier fluid overestimates the value of the hemolysis index by almost one order of magnitude.

Targeting erythrocyte-mediated hypoxia to alleviate lung injury induced by pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PAs) are widely distributed natural toxins and have been extensively studied for their hepatotoxicity. However, PA-induced pulmonary toxicity remains less studied regarding the initiating mechanism and treatment approaches. Our previous study demonstrated the formation of pyrrole-hemoglobin adducts after PA exposure in vivo, which is suspected to affect the oxygen-carrying capacity of erythrocytes [red blood cells (RBCs)] consequently. The present study aimed to investigate the effects of PAs on the oxygen-carrying capacity of RBCs and the potential of targeting RBC-mediated hypoxia to alleviate PA-induced lung injury. First, rats were treated with retrorsine (RTS) or monocrotaline (MCT) intravenously at 0.2mmol/kg. The results of Raman spectrometry analysis on blood samples revealed both RTS and MCT significantly reduced the oxygen-carrying capacity of RBCs. Further, MCT (0.2mmol/kg) was orally given to the rats with or without pretreatment with two doses of erythropoietin (Epo, 500IU/kg/dose every other day), an RBC-stimulating agent. Biochemical and histological results showed pretreatment with Epo effectively reduced the cardiopulmonary toxicity induced by MCT. These findings provide the first evidence that adduction on hemoglobin, and the resulting RBC damage and impaired oxygen-carrying capacity, are the major initiating mechanism underlying PA-induced pulmonary arterial hypertension (PAH), while targeting the RBC damage is a potential therapeutic approach for PA-induced lung injury.

Autologous blood transfusion impedes glycolysis in macrophages to inhibit red blood cell injury in type 2 diabetes through PI3K/Akt/PKM2 signaling axis.

To explore the effect and mechanism of autologous blood transfusion impeding glycolysis in macrophages and inhibiting red blood cells (RBCs) injury in type 2 diabetes through PI3K/Akt/PKM2 signaling axis. Cell transfection were performed and diabetic mice model was constructed. The group were divided into control (NC) and type 2 diabetes model (T2D). T2D model mice were injected with preserved autologous blood, si-PI3K, si-PKM2, si-NC Tran+T2D, (Tran+T2D+si-PI3K, Tran+T2D si-PKM2, Tran+T2D+si-NC) through tail vein. The anti-oxidative effects of transfusion of autologous blood in CD14+ monocytes were detected. The expression of PI3K/Akt/PKM2 protein in CD14+ monocytes were examined by western blot. Effect of autologous blood transfusion ameliorating RBCs injury by regulating PI3K and PKM2 in T2D mice were detected. Effects on oxidative stress in T2D mice were all overturned after autologous blood transfusion in T2D mice. The results manifested that the levels of PI3K, pAkt and PKM2 were downregulated, while the expression of HIF-1α was upregulated in CD14+ monocytes from T2D mice, whereas these influences were all effectively reversed by autologous blood transfusion in T2D mice. The survival rate of RBCs in the serum of T2D mice was declined in the serum of T2D mice, while the effect was reversed by the autologous blood transfusion. Autologous blood transfusion can reduce glycolysis in macrophages and inhibit the release of inflammatory factors through the PI3K/PKM2 signal axis, thereby inhibiting red blood cell damage and improving the oxygen-carrying capacity and survival activity of RBCs in diabetic patients.

ЭФФЕКТИВНОСТЬ ИНФУЗИОННОЙ ТЕРАПИИ ПРИ ЛЕЧЕНИИ СОБАК, БОЛЬНЫХ ПИРОПЛАЗМОЗОМ

The article presents the results of studies obtained in the study of the comparative effectiveness of infusion therapy in the treatment of dogs with pyroplasmosis. Piroplasmosis of dogs is a seasonal, acute, blood–parasitic disease of dogs, which is characterized by fever, liver damage, and destruction of red blood cells. Competent and timely implementation of rehydration infusion therapy for pyroplasmosis is an important component in the complex therapy of sick animals, therefore, the study of the comparative effectiveness of traditional and the introduction into veterinary practice of promising medical detoxification infusion drugs is timely and relevant. In this regard, the aim of the research is to study the comparative effectiveness of infusion therapy in the treatment of dogs with pyroplasmosis. The object of the study were dogs of various breeds with pyroplasmosis and documentation reflecting the state of the incidence of pyroplasmosis of dogs in Rostov–on-Don. To confirm the diagnosis, paired blood serums for serological diagnostics, as well as blood and urine samples for biochemical analysis were sent to the veterinary diagnostic center "Invitro" in Rostov-on-Don. To conduct the experiment (according to the principle of analogues), 3 groups of animals were formed, 5 dogs in each. Treatment of dogs with pyroplasmosis was carried out in a complex, with the mandatory appointment of etiotropic and pathogenetic therapy. The effectiveness of treatment of dogs of the experimental groups was evaluated in dynamics compared with the control group. In the process of implementing the tasks of the experiment, generally accepted methods were used, in accordance with GOST standards, satisfying the objectives of the study. Based on the studies conducted to study the effectiveness of infusion therapy in the treatment of dogs with piroplasmosis, it was found that the use of the drug Reamberin allowed to shorten the recovery period compared to the control group by 5 days, with 1 experimental group – by 2 days. The drug Reamberin has proven to be the most effective infusion drug with antioxidant, hepatoprotective and detoxifying effects.

Intermittent scavenging of storage lesion from stored red blood cells by electrospun nanofibrous sheets enhances their quality and shelf-life

Transfusion of healthy red blood cells (RBCs) is a lifesaving process. However, upon storing RBCs, a wide range of damage-associate molecular patterns (DAMPs), such as cell-free DNA, nucleosomes, free-hemoglobin, and poly-unsaturated-fatty-acids are generated. DAMPs can further damage RBCs; thus, the quality of stored RBCs declines during the storage and limits their shelf-life. Since these DAMPs consist of either positive or negative charged species, we developed taurine and acridine containing electrospun-nanofibrous-sheets (Tau-AcrNFS), featuring anionic, cationic charges and an DNA intercalating group on their surfaces. We show that Tau-AcrNFS are efficient in scavenging DAMPs from stored human and mice RBCs ex vivo. We find that intermittent scavenging of DAMPs by Tau-AcrNFS during the storage reduces the loss of RBC membrane integrity and reduces discocytes-to-spheroechinocytes transformation in stored-old-RBCs. We perform RBC-transfusion studies in mice to reveal that intermittent removal of DAMPs enhances the quality of stored-old-RBCs equivalent to freshly collected RBCs, and increases their shelf-life by ~22%. Such prophylactic technology may lead to the development of novel blood bags or medical device, and may therefore impact healthcare by reducing transfusion-related adverse effects.

Determination of free heme in stored red blood cells with an apo-horseradish peroxidase-based assay.

Transfusion effectiveness of red blood cells (RBCs)has been associated with duration of the storage period. Storage-dependent RBC alterations lead to hemolysis and release of toxic free heme, but the increase of free hemelevels over time is largely unknown. In the current study, an apo-horseradish peroxidase (apoHRP)-based assay was applied to measure levels of free heme atregular intervals or periodically in supernatants of RBCs until a maximum storage period of 42days. Free heme levelsincreased with linear time-dependent kinetics up to day 21 and accelerated disproportionally after day 28 until day 42, as determined with the apoHRP assay. Individual timecourses of free heme in different RBC units exhibited high variability. Notably, levels of free hemoglobin, an established indicator of RBC damage, and those of total hemeincreased with continuous time-dependent linear kinetics over the entire 42day storage period, respectively. Supernatants from RBC units with high levels of free heme ledto inflammatory activation of human neutrophils. In conclusion, determining free heme in stored RBCs with the applied apoHRP assay may become feasible for testing ofRBC storage quality in clinical transfusion medicine.

Effect of Biofunctional Green Synthesized MgO-Nanoparticles on Oxidative-Stress-Induced Tissue Damage and Thrombosis.

The present study describes the green biofunctional synthesis of magnesium oxide (MgO) nanoparticles using the aqueous Tarenna asiatica fruit extract. The characterization of Tarenna asiatica fruit extract MgO nanoparticles (TAFEMgO NPs) was achieved by X-ray powder diffraction, UV-Vis spectroscopy, FTIR, TEM, SEM, and energy-dispersive X-ray diffraction. TAFEMgO NPs scavenged the DPPH free radicals with an IC50 value of 55.95 μg/μL, and it was highly significant compared to the standard. To authenticate the observed antioxidant potential of TAFEMgO NPs, oxidative stress was induced in red blood cells (RBC) using sodium nitrite (NaNO2). Interestingly, TAFEMgO NPs ameliorated the RBC damage from oxidative stress by significantly restoring the stress parameters, such as the protein carbonyl content (PCC), lipid peroxidation (LPO), total thiol (TT), super-oxide dismutase (SOD), and catalase (CAT). Furthermore, oxidative stress was induced in-vivo in Sprague Dawley female rats using diclofenac (DFC). TAFEMgO NPs normalized the stress parameters in-vivo and minimized the oxidative damage in tissues. Most importantly, TAFEMgO NPs restored the function and architecture of the damaged livers, kidneys, and small intestines by regulating biochemical parameters. TAFEMgO NPs exhibited an anticoagulant effect by increasing the clotting time from 193 s in the control to 885 s in the platelet rich plasma. TAFEMgO NPs prolonged the formation of the clot process in the activated partial thromboplastin time and the prothrombin time, suggest the effective involvement in both intrinsic and extrinsic clotting pathways of the blood coagulation cascade. TAFEMgO NPs inhibited adenosine di-phosphate (ADP)-induced platelet aggregation. TAFEMgO NPs did not show hemolytic, hemorrhagic, and edema-inducing properties at the tested concentration of 100 mg/kgbody weight, suggesting its non-toxic property. In conclusion, TAFEMgO NPs mitigates the sodium nitrite (NaNO2)- and diclofenac (DFC)-induced stress due to oxidative damage in both in vitro and in vivo experimental models.

Superior Hemostatic and Wound-Healing Properties of Gel and Sponge Forms of Nonoxidized Cellulose Nanofibers: In Vitro and In Vivo Studies.

Many materials have been engineered and commercialized as hemostatic agents. However, there is still a gap in the availability of hemostats that offer biocompatibility and biodegradability in combination with effective hemostatic properties. Cellulose nanofibers are investigated as hemostatic materials with most studies focusing on oxidized cellulose-derived hemostats. The recent studies demonstrate that by optimizing the morphological properties of nonoxidized cellulose nanofibers (CNFs) enhanced hemostasis is achieved. Herein, the hemostatic and wound-healing properties of CNFs with optimized morphology using two forms, gel, and sponge is investigated. In vitro thromboelastometry studies demonstrate that CNFs reduce clotting time by 68% (±SE 2%) and 88% (±SE 5%) in gel and sponge forms, respectively. In an in vivo murine liver injury model, CNFs significantly reduce blood loss by 38% (±SE 10%). The pH-neutral CNFs do not damage red blood cells, nor do they impede the proliferation of fibroblast or endothelial cells. Subcutaneously-implanted CNFs show a foreign body reaction resolving with the degradation of CNFs on histological examination and there is no scarring in the skin after 8 weeks. Demonstrating superior hemostatic performance in a variety of forms, as well as biocompatibility and biodegradability, CNFs hold significant potential for use in surgical and first-aid environments.