Blood Cell Damage Research Articles

Chemical Composition, Antioxidant, Antibacterial, and Hemolytic Properties of Ylang-Ylang (Cananga odorata) Essential Oil: Potential Therapeutic Applications in Dermatology

Background/Objectives: This study investigates the chemical composition, antioxidant, antibacterial, and hemolytic properties of ylang-ylang (Cananga odorata) essential oil, with a focus on its potential therapeutic applications for dermatological diseases and the importance of transforming such bioactive properties into a stable, safe, and effective formulation. Methods/Rsults: Essential oils were extracted from flowers harvested in northern Grande Comore using hydro distillation at three different distillation times to examine the impact on yield and quality. Gas chromatographic analysis identified a complex mixture of compounds, including linalool, geranyl acetate, and benzyl benzoate. Antioxidant activity was assessed using DPPH, FRAP, TAC, and beta-carotene bleaching inhibition assays, revealing significant radical scavenging capabilities, with DPPH IC50 varying between 1.57 and 3.5 mg/mL. Antibacterial activity was tested against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa, showing promising inhibition zones and minimum inhibitory concentrations. Hemolytic tests indicated varying degrees of red blood cell damage, emphasizing the need for careful concentration management in therapeutic applications. Molecular docking studies highlighted potential therapeutic targets for dermatological conditions, identifying high binding affinities for specific compounds against proteins involved in acne, eczema, and psoriasis. Conclusions: This comprehensive analysis underscores the potential of ylang-ylang essential oil (YEOs) as a natural alternative for antimicrobial treatments and dermatological applications, with its success dependent on optimized extraction methods and precise formulation to reduce cytotoxic effects. A formulation approach is crucial to ensure controlled release, improve bioavailability, and minimize skin irritation.

Per- and Polyfluoroalkyl Substances in the Duluth, Minnesota Area: Exposure to and Biomarker Responses in Tree Swallows Relative to Known Fire-Fighting Foam Sources.

Tree swallow nest boxes were deployed at sites proximal to two putative aqueous film forming foam (AFFF) sources in the Duluth, MN area, as well as along the St. Louis River and a reference lake for comparative purposes in 2019, 2020 and 2021. The two AFFF sites were the current Duluth Air National Guard Base (ANG) and the Lake Superior College Emergency Response Training Center. Between 13 and 40 per- and polyfluoroalkyl substances (PFAS), depending on year, were detected and quantified in tree swallow egg, nestling carcasses, and stomach contents. Assessments were made of oxidative stress and ethoxyresorufin-O-dealkylase activity in liver tissue, thyroid hormone levels in plasma and thyroid glands, DNA damage in red blood cells, and two measures of immune response (haptoglobin-like activity and immunoglobulin) in plasma of the nestlings. Additionally, other contaminants, such as polychlorinated biphenyls, legacy organochlorine pesticides, and trace elements, were assessed at sites with no previous data. Total egg PFAS concentrations at the ANG site and north of that site were 30-40 times higher than at the reference lake, while nestling PFAS concentrations were 10-15 times higher. In contrast, the St. Louis River sites had slightly, but non-statistically significant, elevated egg and nestling PFAS concentrations relative to the reference lake (2-5 times higher). One PFAS, perfluorohexane sulfonate (PFHxS), was higher, as a proportion of total PFAS, at sites with a known AFFF source compared to the reference lake, as well as compared to sites along the St. Louis River with mainly urban and industrial sources of PFAS. The ratio of total carboxylates to total sulfonates also distinguished between PFAS sources. There were few to no differences in biomarker responses among sites, and no association with PFAS exposure.

Hydrogen bonding-mediated interaction underlies the enhanced membrane toxicity of chemically transformed polystyrene microplastics by cadmium

The global attention on microplastic pollution and its implications for human health has grown in recent years. Additionally, the co-existence of heavy metals may significantly alter microplastics’ physicochemical characteristics, potentially amplifying their overall toxicity—a facet that remains less understood. In this study, we focused the membrane toxicity of modified polystyrene microplastics (PS-MPs) following cadmium (Cd) pretreatment. Our findings revealed that Cd-pretreated PS-MPs exacerbated their toxic effects, including diminished membrane integrity and altered phase fluidity in simulated lipid membrane giant unilamellar vesicles (GUVs), as well as heightened membrane permeability, protein damage, and lipid peroxidation in red blood cells and macrophages. Mechanistically, these augmented membrane toxicities can be partially ascribed to modifications in the surface roughness and hydrophilicity of Cd-pretreated PS-MPs, as well as to interactions between PS-MPs and lipid bilayers. Notably, hydrogen bonds emerged as a crucial mechanism underlying the enhanced interaction of PS-MPs with lipid bilayers.

Simulation of the effect of hemolysis on thrombosis in blood-contacting medical devices

Heart failure, broadly characterized by the gradual decline of the ability of the heart to maintain adequate blood flow throughout the body's vascular network of veins and arteries, is one of the leading causes of death worldwide. Mechanical Circulatory Support is one of the few available alternative interventions for late-stage heart failure with reduced ejection fraction. A ventricular assist device is surgically implanted and connected to the left and or right heart ventricles to provide additional bloodflow, off-loading the work required by the heart to maintain circulation. Modern mechanical circulatory support devices generate non-physiological flow conditions that can lead to the damage and rupture of blood cells (hemolysis), and the formation of blood clots (thrombosis), which pose severe health risks to the patient. It is essential to improve prediction tools for blood damage to reduce the risk of hemolysis and thrombosis. A simulation-based approach examines the interaction between hemolysis and thrombosis. Incompressible finite-volume computational fluid dynamics simulations are executed on an open-hub axial flow ventricular assist device. A continuum model of thrombosis and the intrinsic coagulation process is extended to include the effect of hemolysis. The model accounts for the effect of activation of platelets by shear stress, paracrine signaling, adhesion, and hemoglobin and ADP released during hemolysis. The effect of hemolysis with thrombosis is modelled by accounting for the hyper-adhesivity of von-Willebrand Factor on extracellular hemoglobin, and the increased rate of platelet activation induced by ADP release. Thrombosis is assessed at varying inflow rates and rotor speeds, and cases are executed where thrombosis is affected by ADP release and Hb-induced hyper-adhesivity. It is found that there is a non-negligible effect from hemolysis on thrombosis across a range of rotor speeds, and that hyperadhesivity plays a dominant role in thrombus formation in the presence of hemolysis.

Genotoxic effect of selenium arabinogalactan nanocomposite on nucleated blood cells

Introduction. Selenium (Se) nanoparticles have attracted the interest of researchers for various applications due to their unusual properties. Despite their advantages, Se nanoparticles also have toxic effects, so for their successful use it is necessary to know the doses that are safe for the use. An important component in the development of pathological processes is the occurrence of DNA damage after exposure to Se nanoparticles, which can lead to severe disorders. Materials and methods. Male white rats were orally administered a solution of Se nanocomposite at a dose of 500 μg/kg for 10 days. The genotoxicity of the nanocomposite under study was assessed by the occurrence of DNA damage in blood cells using the DNA comet method in the alkaline version. The results were obtained during 2 stages: one day after exposure and after 4 months to identify the persistence or absence of a negative effect. Results. With using the DNA comet method, intragastric administration of Se nanocomposite was found to cause the damage to the DNA structure, and this effect persists not only 24 hours after exposure, but also 4 months later. Limitations. The study is limited to the study of DNA fragmentation on the next day after a 10-day exposure to Se nanocomposite in male white rats and during the long-term period after 4 months. Conclusion. The study revealed persistent DNA damage in the nucleated blood cells of male albino rats, which apparently may be associated with the main mechanism of Se toxicity: nonspecific replacement of sulfur in sulfur-containing amino acids. However, the toxic effects of the nanocomposite may also be caused by its pro-oxidant properties, which requires further confirmation.

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

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

Analysis of non-physiological shear stress-induced red blood cell trauma across different clinical support conditions of the blood pump.

Systematic research into device-induced red blood cell (RBC) damage beyond hemolysis, including correlations between hemolysis and RBC-derived extracellular vesicles, remains limited. This study investigated non-physiological shear stress-induced RBC damage and changes in related biochemical indicators under two blood pump clinical support conditions. Pressure heads of 100 and 350mmHg, numerical simulation methods, and two in vitro loops were utilized to analyze the shear stress and changes in RBC morphology, hemolysis, biochemistry, metabolism, and oxidative stress. The blood pump created higher shear stress in the 350-mmHg condition than in the 100-mmHg condition. With prolonged blood pump operation, plasma-free hemoglobin and cholesterol increased, whereas plasma glucose and nitric oxide decreased in both loops. Notably, plasma iron and triglyceride concentrations increased only in the 350-mmHg condition. The RBC count and morphology, plasma lactic dehydrogenase, and oxidative stress across loops did not differ significantly. Plasma extracellular vesicles, including RBC-derived microparticles, increased significantly at 600min in both loops. Hemolysis correlated with plasma triglyceride, cholesterol, glucose, and nitric oxide levels. Shear stress, but not oxidative stress, was the main cause of RBC damage. Hemolysis alone inadequately reflects overall blood pump-induced RBC damage, suggesting the need for additional biomarkers for comprehensive assessments.

Effect of veno-arterial extracorporeal membrane oxygenation lower-extremity cannulation on intra-arterial flow characteristics, oxygen content, and thrombosis risk

PurposeThis study aimed to investigate the effects of lower-extremity cannulation on the intra-arterial hemodynamic environment, oxygen content, blood damage, and thrombosis risk under different levels of veno-arterial (V-A) ECMO support. MethodsComputational fluid dynamics methods were used to investigate the effects of different levels of ECMO support (ECMO flow ratios supplying oxygen-rich blood 100–40 %). Flow rates and oxygen content in each arterial branch were used to determine organ perfusion. A new thrombosis model considering platelet activation and deposition was proposed to determine the platelet activation and thrombosis risk at different levels of ECMO support. A red blood cell damage model was used to explore the risk of hemolysis. ResultsOur study found that partial recovery of cardiac function improved the intra-arterial hemodynamic environment, with reduced impingement of the intra-arterial flow field by high-velocity blood flow from the cannula, a flow rate per unit time into each arterial branch closer to physiological levels, and improved perfusion in the lower extremities. Partial recovery of cardiac function helps reduce intra-arterial high shear stress and residence time, thereby reducing blood damage. The overall level of hemolysis and platelet activation in the aorta decreased with the gradual recovery of cardiac contraction function. The areas at high risk of thrombosis under V-A ECMO femoral cannulation support were the aortic root and the area distal to the cannula, which moved to the descending aorta when cardiac function recovered to 40–60 %. However, with the recovery of cardiac contraction function, hypoxic blood pumped by the heart is insufficient in supplying oxygen to the front of the aortic arch, which may result in upper extremity hypoxia. ConclusionWe developed a thrombosis risk prediction model applicable to ECMO cannulation and validated the model accuracy using clinical data. Partial recovery of cardiac function contributed to an improvement in the aortic hemodynamic environment and a reduction in the risk of blood damage; however, there is a potential risk of insufficient perfusion of oxygen-rich blood to organs.

Assessment of dietary polyvinylchloride, polypropylene and polyethylene terephthalate exposure in Nile tilapia, Oreochromis niloticus: Bioaccumulation, and effects on behaviour, growth, hematology and histology

Microplastics (MPs) have been recognized as emerging aquatic pollutants receiving major concern due to their detrimental effects on aquatic life. Nile Tilapia, Oreochromis niloticus is a model species considered in toxicological studies to address the effects of pollutants in freshwater animals. However, comprehensive knowledge comparing the impacts on fish across various MPs polymers is scarce. Therefore, the overarching aim of the current study was to examine the bioconcentration of MPs polymers: polyvinylchloride (PVC), polypropylene (PP), and polyethylene terephthalate (PET), and their toxic effects on growth, and behavioral responses, hematology, and histology of gills, liver, and intestine in O. niloticus. Fishes were subjected to a 21-day dietary exposure to MPs by assigning them into six treatment groups: T1 (4% of PVC), T2 (4% of PP), T3 (4% of PET), T4 (8% of PVC), T5 (8% of PP), T6 (8% of PET), and control (0% of MPs), to assess the effects on fish across the polymers and dosage. Results showed several abnormalities in anatomical and behavioral parameters, lower growth, and high mortality in MPs-exposed fish, indicating a dose-dependent relationship. The elevated dosage of polymers raised the bioavailability of PVC, PP, and PET in gills and gut tissues. Noteworthy erythrocyte degeneration referred to cytotoxicity and stress imposed by MPs, whereas the alterations in hematological parameters were possibly due to blood cell damage, also indicating mechanisms of defense against MPs toxicity. Histopathological changes in the gills, liver, and intestine confirmed the degree of toxicity and associated dysfunctions in fish. A higher sensitivity of O. niloticus to PET-MPs compared to other polymers is likely due to its chemical properties and species-specific morphological and physiological characteristics. Overall, the present study reveals valuable insights into the emerging threat of MPs toxicity in freshwater species, which could be supportive of future toxicological research.

Considerations for deriving a safe intake of propylene glycol

The use of propylene glycol (PG) in food and other applications is widespread, and some estimates of dietary exposure to PG approach or exceed the Acceptable Daily Intake (ADI) of 25 mg/kg bw-day. The current ADI for PG applies a cumulative uncertainty factor of 100, which includes factors of 10 for both interspecies and intraspecies differences. Available toxicology studies and human data, however, indicate a plausible mode of action (MoA) that would support a chemical-specific adjustment factor (CSAF) of 1 for interspecies toxicodynamic differences, reducing the total uncertainty factor from 100 to 40. The MoA involves an increase in serum PG concentrations after metabolic saturation, leading to serum hyperosmolarity, which can ultimately cause hemolytic changes and red blood cell damage. Therefore, the species similarities in toxicodynamic response for this critical effect could support increasing the ADI from 25 to 62.5 mg/kg bw-day, applicable to both children and adults.

Effects of methanolic leaf extract and fractions of Irvingia gabonensis on hematological parameters in Wistar rats with splenomegaly

Splenomegaly is a medical condition characterized by an enlargement of the spleen, an organ located in the upper left part of the abdomen, beneath the ribcage. The spleen plays various essential roles in the body, including filtering blood, removing old or damaged blood cells, and helping the immune system by producing and storing immune cells. Splenomegaly causes negative haematological effects. It is very common in Africa and Asia. The aim of this study is to investigate the effect of methanol leaf extract and fractions of Irvingia gabonensis on haematological parameters in splenomegaly-induced Wistar rats. Extraction and fractionation of the plant were carried out through standard procedure using methanol, hexane, butanol and ethyl acetate. A qualitative phytochemical evaluation of the plant was done. The effects of the extract and fractions of Irvingia gabonensis were investigated using a rat model. The presence of various phytochemicals like alkaloids, flavonoids, steroids, terpenoids, and tannins was observed in the extract and fractions of the plant. The methanolic extract and ethylacetate fraction significantly caused the normalization of PCV, HB, and RBC post-treatment. The findings from this study suggest that Irvingia gabonensis could be researched further for the management of splenomegaly and also the isolation of phytochemicals responsible for these effects.

Genoprotective Effects of Quercetin against Genotoxic Damage in Peripheral Blood Cells of Healthy Individuals and Tuberculosis Patients

Tuberculosis (TB) is a bacterial infection caused by the bacterium Mycobacterium tuberculosis (Mtb) and has long been one of the leading causes of death worldwide. Flavonoids are among the most thoroughly researched natural compounds found in plants. They have been widely recognized for their diverse medicinal properties, including antimicrobial, antioxidant, antiinflammatory and anticancer. Flavonoids have antioxidant properties and have been shown to exert anti-pathogenic potential, but few studies have examined their effects on Mycobacterium tuberculosis (Mtb) infection. The aim of the current study was to investigate in vitro the protective effect of the flavonoid, quercetin on hydrogen peroxide (H2O2)-induced oxidative DNAdamage, using the Comet assay and the micronucleus (MN) test in peripheral lymphocytes from tuberculosis patients (TB)and compared with lymphocytes from healthy individuals. Quercetin significantly reduced DNA damage and reduction in the frequency of micronuclei in TB patient compared with healthy individuals. These findings show that the nano-quercetin has genoprotective and enzyme modulating effects and highlight its potential as a possible therapeutic supplement for TB patients.

DNA base oxidation in relation to TNM stages and chemotherapy treatment in colorectal cancer patients 2–9 months post-surgery

Accumulation of DNA damage is a critical feature of genomic instability, which is a hallmark of various cancers. The enzyme-modified comet assay is a recognized method to detect specific DNA lesions at the level of individual cells. In this cross-sectional investigation, we explore possible links between clinicopathological and treatment related factors, nutritional status, physical activity and function, and DNA damage in a cohort of colorectal cancer (CRC) patients with non-metastatic disease. Levels of DNA damage in peripheral mononuclear blood cells (PBMCs) assessed 2–9 months post-surgery, were compared across tumour stage (localized (stage I-II) vs. regional (stage III) disease), localization (colon vs. rectosigmoid/rectum cancer), and adjuvant chemotherapy usage, with the last dosage administrated 2–191 days prior to sampling. Associations between DNA damage and indicators of nutritional status, physical activity and function were also explored. In PBMCs, DNA base oxidation was higher in patients diagnosed with regional compared with localized tumours (P = 0.03), but no difference was seen for DNA strand breaks (P > 0.05). Number of days since last chemotherapy dosage was negatively associated with DNA base oxidation (P < 0.01), and patients recently receiving chemotherapy (<15 days before blood collection) had higher levels of DNA base oxidation than those not receiving chemotherapy (P = 0.03). In the chemotherapy group, higher fat mass (in kg and %) as well as lower physical activity were associated with greater DNA base oxidation (P < 0.05). In conclusion, DNA base oxidation measured with the enzyme-modified comet assay varies according to tumour and lifestyle related factors in CRC patients treated for non-metastatic disease.

Analysis of the Suitability of an Effective Viscosity to Represent Interactions Between Red Blood Cells in Shear Flow.

Many methods to computationally predict red blood cell damage have been introduced, and among these are Lagrangian methods that track the cells along their pathlines. Such methods typically do not explicitly include cell-cell interactions. Due to the high volume fraction of red blood cells (RBCs) in blood, these interactions could impact cell mechanics and thus the amount of damage caused by the flow. To investigate this question, cell-resolved simulations of red blood cells in shear flow were performed for multiple interacting cells, as well as for single cells in unbounded flow at an effective viscosity. Simulations run without adjusting the bulk viscosity produced larger errors unilaterally and were not considered further for comparison. We show that a periodic box containing at least 8 cells and a spherical harmonic of degree larger than 10 are necessary to produce converged higher-order statistics. The maximum difference between the single-cell and multiple-cell cases in terms of peak strain was 3.7%. To achieve this, one must use the whole blood viscosity and average over multiple cell orientations when adopting a single-cell simulation approach. The differences between the models in terms of average strain were slightly larger (maximum difference of 6.9%). However, given the accuracy of the single-cell approach in predicting the maximum strain, which is useful in hemolysis prediction, and its computational cost that is orders of magnitude less than the multiple-cell approach, one may use it as an affordable cell-resolved approach for hemolysis prediction.

Pharmacokinetics of Glutapyrone and its Impact on Expression of the Genes Involved in DNA Repair and Free Radical Production in Intact and Diabetic Rats

Abstract Modification of expression of several genes encoding enzymes involved in radical production and DNA repair by a 1,4-DHP derivative glutapyrone was studied in intact rats and animals with streptozotocin diabetes mellitus. Glutapyrone stimulated iNos mRNA production in both kidneys and blood. The effect was stronger in kidneys of diabetic animals, however in blood the expression was down-regulated. The compound increased the Parp 1 gene expression in kidneys of both intact and diabetic animals; in blood the effect was adverse. Expression of XDh gene was significantly increased by glutapyrone in kidneys of intact and diabetic animals. Administration of the compound to intact animals triggered significant increase of DNA damage in white blood cells assayed by comet assay; in diabetic animals no effect was produced. To explain discrepancies with the formerly described effects of glutapyrone on cultured cells, metabolism of the compound was studied. Glutapyrone is either oxidised or the residue of glutamic acid is removed, glutapyrone turns into AV-153, and the latter is metabolised to smaller compounds. Formation of AV-153, a DNA binder and genotoxic compound in high concentrations, can explain DNA damage in white blood cells and stimulation of DNA repair.

In Vitro Protective Effects of Aqueous and Alcoholic Extracts of Caryophyllus aromaticus on Reducing H2O2-Induced DNA Damage in Human Mononuclear White Blood Cells

In Vitro Protective Effects of Aqueous and Alcoholic Extracts of Caryophyllus aromaticus on Reducing H2O2-Induced DNA Damage in Human Mononuclear White Blood Cells

Multi-Omics Analysis of the Impact of Long Distance Trail Running on Red Blood Cells Highlights Acylcarnitine Mediated Lipid Damage Repair Mechanisms

Red blood cells (RBC) play critical roles in the maintenance of vascular tone and metabolite transfer in addition to their well characterized role in gas exchange. In this capacity, they play a central role in maintaining systemic activity during stressful physiological situations such as exercise. At the far end of the spectrum for endurance sports, the popularity of long-distance running has been increasing in recent years. However, literature on the impact of marathon and ultramarathon running on red blood cell physiology is limited. To characterize molecular responses in RBC to long-distance running, blood was sampled from 11 runners before and after the Martigny-Combes à Chamonix (MCC, distance: 40 km, elevation gain: 2300 m) or 12 runners before and after the Ultra - Trail du Mont Blanc (UTMB, distance: 171 km, elevation gain: 10,000 m) and separated into plasma and RBC components. Hematological parameters and RBC deformability were assessed before and after each race. 1 Here, the same samples were analyzed using mass spectrometry-based metabolomics, lipidomics, proteomics, and elemental analysis ( Figure 1A). While RBC after both races had decreased mean cell volume (MCV), RBC exhibited higher amounts of exposed phosphatidylserine (PS) on the outer membrane only after the MCC, which serves as a signal for eryptosis. However, hematocrit (Hct) remained unchanged after this race, but was significantly lower after the UTMB. 1 Although decreased Hct can result from hemodilution, the plasma levels of albumin, sodium, and potassium were not significantly altered in either race. In addition, RBC microparticles increased after the UTMB with concomitant decreases in the deformability of intact RBC at high shear stresses, effects of which were not observed after the MCC. Intracellular metabolic correlates with deformability were enriched with acylcarnitines (AC - Figure 1A), which inversely correlated with RBC deformability at 30 Pa. This compound class was also positively associated with the level of IL-6 in addition to kynurenine, an immunomodulatory metabolite which has also been linked to IL-6 level and RBC damage in COVID19. 2 Within RBC, that are largely devoid of mitochondria, AC play an intermediary role in membrane lipid repair ( Figure 1A). While AC and fatty acids were significantly higher after both races, the magnitude of increase was higher after the MCC ( Figure 1B). However, the ratios of lysophosphatidylcholines or lysophosphatidylethanolamines to their respective intact lipid counterparts were predominantly lower after the UTMB, indicating more active membrane lipid repair in these cells ( Figure 1B). In support, the coenzyme A precursor pantothenate was consumed after both races, though carnitine accumulated only after the UTMB possibly due to increased acyl-CoA utilization for lipid repair rather than interconversion into AC. Increased oxidative stress was also apparent in the proteome, which demonstrated that the proportion of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) with irreversibly oxidized active site cysteine was significantly higher after the UTMB. As this protein plays a key regulatory role in glucose oxidation by mediating fluxes through glycolysis or the pentose phosphate pathway (PPP) in an oxidative stress-dependent fashion, 3 increased damage to its active site may partially explain a shift in glucose catabolism away from glycolysis and towards the PPP to generate NADPH reducing equivalents to cope with accumulating oxidative stress. In consideration of the varying temporal exposures to physiological stress between the MCC and UTMB, these results provide an in vivo snapshot into the accumulation of damage, repair, and removal of RBC as they circulate throughout the body during exercise. 1. Robert M, Stauffer E, Nader E, et al. Impact of Trail Running Races on Blood Viscosity and Its Determinants: Effects of Distance. Int. J. Mol. Sci. 2020;21(22):8531. 2. Thomas T, Stefanoni D, Dzieciatkowska M, et al. Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients. J. Proteome Res. 2020;19(11):4455-4469. 3. Reisz JA, Wither MJ, Dzieciatkowska M, et al. Oxidative modifications of glyceraldehyde 3-phosphate dehydrogenase regulate metabolic reprogramming of stored red blood cells. Blood. 2016;128(12):e32-e42.

One-pot synthesis of ultra-stable polyvinylpyrrolidone-modified MnO2 nanoparticles for efficient radiation protection

Radiobiological damage can be caused by radiation, and easy preparation of long-term stable radioprotectors is helpful for timely and efficient response to radiation emergencies. This study develops an ultra-stable radioprotector for rapid nuclear emergency with a simple preparing method. First of all, polyvinylpyrrolidone-modified MnO2 nanoparticles (PVP-MnO2 NPs) are obtained by one-pot synthesis with ultra-stability (remaining for at least three years) and multiple free radical scavenging activities. In the synthesis process, PVP acts as a reducing agent, a surfactant (soft template), and a steric stabilizer. PVP-MnO2 NPs can improve the survival rates of irradiated cells by effectively scavenging free radicals and protecting DNA from radiation damage. Besides, PVP-MnO2 NPs can also prevent peripheral blood cell and organ damage induced by radiation, and improve the survival rate of irradiated mice. Finally, PVP-MnO2 NPs are mainly metabolized by liver and kidney in mice, and basically excreted 72 h after administration. These results indicate that PVP-MnO2 NPs exhibit good biosafety and radioprotection activity, which is significant for the development of radioprotection agents.

Characterization and Expression Analysis of Genes from Megalobrama amblycephala Encoding Hemoglobins with Extracellular Microbicidal Activity.

Hemoglobin (Hb) usually comprises two α and two β subunits, forming a tetramer responsible for oxygen transportation and storage. Few studies have elucidated fish hemoglobin immune functions. Megalobrama amblycephala is a freshwater-cultured fish prevalent in China. We identified two M. amblycephala hemoglobin subunits and analyzed their expression patterns and antibacterial activities. The respective full-length cDNA sequences of the M. amblycephala Hb α (MaHbα) and β (MaHbβ) subunits were 588 and 603 bp, encoding 143 and 148 amino acids. MaHbα and MaHbβ were highly homologous to hemoglobins from other fish, displaying typical globin-like domains, most heme-binding sites, and tetramer interface regions highly conserved in teleosts. In phylogenetic analyses, the hemoglobin genes from M. amblycephala and other cypriniformes clustered into one branch, and those from other fishes and mammals clustered into other branches, revealing fish hemoglobin conservation. These M. amblycephala Hb subunits exhibit different expression patterns in various tissues and during development. MaHbα is mainly expressed in the blood and brain, while MaHbβ gene expression is highest in the muscle. MaHbα expression was detectable and abundant post-fertilization, with levels fluctuating during the developmental stages. MaHbβ expression began at 3 dph and gradually increased. Expression of both M. amblycephala Hb subunits was down-regulated in most examined tissues and time points post-Aeromonas hydrophila infection, which might be due to red blood cell (RBC) and hematopoietic organ damage. Synthetic MaHbα and MaHbβ peptides showed excellent antimicrobial activities, which could inhibit survival and growth in five aquatic pathogens. Two M. amblycephala hemoglobin subunits were identified, and their expression patterns and antibacterial activities were analyzed, thereby providing a basis for the understanding of evolution and functions of fish hemoglobins.

Benchmark dose estimation of polycyclic aromatic hydrocarbons exposure base on Bayesian kernel machine regression

Objective: To explore benchmark dose (BMD) estimations of polycyclic aromatic hydrocarbons (PAHs) based on Bayesian kernel machine regression (BKMR) . Methods: A total of 155 adult residents of a coking plant in Shanxi Province who were surveyed in summer (June to August) from 2014 to 2019 were selected as the research objects. Fasting elbow vein blood of the subjects was collected in the morning for automatic analysis and detection of blood routine. Morning urine samples were collected for automatic analysis and detection of urine routine and urine creatinine detection. BKMR model combined with BMD method was used to calculate the acceptable doses of PAHs exposure on red blood cell damage in non-occupational population. Results: The concentration of hydroxylpolycyclic aromatic hydrocarbons (OH-PAHs) in the red blood cells abnormal group (n=117) was significantly higher than that in the normal group (n=38) (P<0.01). In the combined effect of OH-PAHs, 2-hydrol-naphthalene contributed the most, and the posterior inclusion probability (PIP) value was 0.9354. When OH-PAHs ≥P(55) concentration, the joint effect on the risk of red blood cell abnormalities increased as the concentration of the OH-PAHs mixture increased. When OH-PAHs were at P(65) and P(75) concentrations, respectively, the risk of red blood cell abnormalities in adults were 3.09 and 4.98 times that of OH-PAHs at P(50) concentrations, respectively. Compared with high concentration, low concentration of OH-PAHs exposure was more sensitive to red blood cell darmage. The acceptable doses of 8 kinds of OH-PAHs were 1.010 μmol/mol Cr (2-hydrol-naphthalene), 0.743 μmol/mol Cr (1-hydrol-naphthalene), 0.901 μmol/mol Cr (2-hydroxy-fluorene) and 0.775 μmol/mol Cr (1-hydroxy-phenanthrene), 0.737 μmol/mol Cr (1-hydroxy-pyrene), 0.607 μmol/mol Cr (9-hydroxy-fluorene), 0.713 μmol/mol Cr (2-hydroxy-phenanthrene) and 0.628 μmol/mol Cr (3-hydroxybenzo[a] pyrene), respectively. Conclusion: OH-PAHs mixture has positive combined effect on red blood cell damage in non-occupational population, and low concentration of OH-PAHs exposure is more sensitive to red blood cell damage. It is recommended that the exposure dose of PAHs should be controlled within 1 μmol/mol Cr.