Erythroid Research Articles

Effects of Pollution on the Haematology of Cyprinus carpio Inhabiting two Government Sponsored Fish Ponds in East Khasi Hills District, Meghalaya, India

Adult Cyprinus carpio were collected from two government sponsored fish ponds located at Fish Dale and Laitkyrhong, East Khasi Hills District, Meghalaya, India. The effects of pollutants on haematological parameters of Cyprinus carpio were studied. The results showed a decline in RBC and WBC count and haemoglobin content in fishes collected from Laitkyrhong. Micronucleus assaywas carried out following standard protocols and observations were made using Olympus, BX- 53 image analyser, CellSens Standard (software). Analysis showed a number of micronucleus and nuclear abnormalities of the erythrocytes of Cyprinus carpio from Laitkyrhong as compared to fishes from Fish Dale. Scanning Electron Microscopy study revealed swollen erythrocytes called spherocytes, ruptured erythrocytes and crenations at the erythrocyte membranes while the control erythrocytes showed normal features. The Energy Dispersive X-ray Spectroscopic analysis was by INCA-7582 (Oxford) Energy Dispersive X-ray microanalyser equipped with a Si (Li) high resolution detector attached to the scanning electron microscope, JSM-6360 (Jeol). Differences in the EDS spectra of RBCs from control, Laitkyrhong and Fish Dale fishes were observed to be in terms of Silicon (Si), Aluminium (Al) and Titanium (Ti) were absent in the control sample. The presence of silicon in erythrocytes of fishes inhabiting Fish Dale and Laitkyrhong area suggests that silicon may be the main factor for the various deformities in the haematological parameters of Cyprinus carpio. The deformities observed may affect the growth and survival of these fishes. Therefore, there is a constant need to check the flow of polluted waters in the rearing ponds especially during the rainy seasons. The present study suggests that haematological study may serve as a tool in determining the health of the fish and the type of environment in which it lives.

Erythrocytes' surface properties and stiffness predict survival and functional decline in ALS patients.

Erythrocytes play a fundamental role in oxygen delivery to tissues and binding to inflammatory mediators. Evidences suggest that dysregulated erythrocyte function could contribute to the pathophysiology of several neurodegenerative diseases. We aimed to evaluate changes in morphological, biomechanical, and biophysical properties of erythrocytes from amyotrophic lateral sclerosis (ALS) patients, as new areas of study in this disease. Blood samples were collected from ALS patients, comparing with healthy volunteers. Erythrocytes were assessed using atomic force microscopy (AFM) and zeta potential analysis. The patients' motor and respiratory functions were evaluated using the revised ALS Functional Rating Scale (ALSFRS-R) and percentage of forced vital capacity (%FVC). Patient survival was also assessed. Erythrocyte surface roughness was significantly smoother in ALS patients, and this parameter was a predictor of faster decline in ALSFRS-R scores. ALS patients exhibited higher erythrocyte stiffness, as indicated by reduced AFM tip penetration depth, which predicted a faster ALSFRS-R score and respiratory subscore decay. A lower negative charge on the erythrocyte membrane was predictor of a faster ALSFRS-R and FVC decline. Additionally, a larger erythrocyte surface area was an independent predictor of lower survival. These changes in morphological and biophysical membrane properties of ALS patients' erythrocytes, lead to increased cell stiffness and morphological variations. We speculate that these changes might precipitate motoneurons dysfunction and accelerate disease progression. Further studies should explore the molecular alterations related to these observations. Our findings may contribute to dissect the complex interplay between respiratory function, tissue hypoxia, progression rate, and survival in ALS.

Жирные кислоты мембран эритроцитов в дифференцировании пациентов с жировой болезнью печени алкогольного, неалкогольного и смешанного генеза

The purpose of the study: to study the possibilities of using fatty acids of erythrocyte membranes in differentiating patients with fatty liver disease of alcoholic, non-alcoholic and mixed genesis (metabolic + alcohol). Material and methods. 38 men (average age 47.5 ± 2.9 years) with non-alcoholic fatty liver disease (NAFLD); 31 men with alcoholic fatty liver disease (AFLD) (45.1 ± 3.1 years) and 30 men (48.2 ± 3.2 years) with fatty liver disease of mixed genesis (metabolic + alcoholic) were examined. The degree of fibrosis in the groups did not exceed grade I. The composition and levels of the fatty acids (FA) of erythrocyte,s membranes were studied using gas chromatography/mass spectrometry, a system based on three Agilent 7000B quadrupoles (USA). Results. The levels of elaidic, 9-palmitoleic, eicosapentaenoic fatty acids were higher (p = 0.041–0.058), and the content of margaric, stearic and alpha-linolenic acids (p = 0.043–0.05) were lower in alcoholic genesis compared with non-alcoholic. The use of a panel of fatty acids – C18:1;t9, C17:0, C18:0, C18:3 n-3, C16:1;9, C20:5 n-3 – provided high diagnostic accuracy with an AUC of 0.914, sensitivity of 81%, specificity of 93% when distinguishing NAFLD from AFLD. It was found that the total content of unsaturated, monounsaturated, levels of arachidonic (n-6), oleic, eicosapentaenoic (n-3), palmitoleic, elaidic, the total content of two n-3 PUFA – eicosapentaenoic and docosahexaenoic in patients with mixed-genesis fatty liver disease were statistically significantly higher, and the levels of stearic, the total content of saturated, arachinic and the ratios of saturated FA/unsaturated FA, saturated FA/polyunsaturated FA were lower than in patients with non–alcoholic fatty liver disease (p = 0.000004–0.04). In patients with fatty liver disease of mixed genesis, the total content of monounsaturated FA, especially oleic and palmitoleic, linoleic (n-6) and saturated lauric, were significantly higher, and the levels of saturated FA arachinic, stearic, SFA/USFA, SFA/PUFA ratios were lower than in AFLD (p = 0.0009–0.06). Conclusion. The revealed differences in the levels of fatty acids of erythrocyte membranes in patients with fatty liver disease of various origins are probably associated with the main etiological factor and can be used to develop new diagnostic methods and targets for therapy.

A Biomimetic Upconversion Nanobait-Based Near Infrared Light Guided Photodynamic Therapy Alleviates Alzheimer's Disease by Inhibiting β-Amyloid Aggregation.

Aberrant β-amyloid (Aβ) fibrillation is the key event in Alzheimer's disease (AD), the inhibition and degradation of which are recognized as a promising therapeutic strategy to alleviate the nerve damage of AD. Photodynamic therapy (PDT) holds great potential for modulation of Aβ self-assembly, which is nevertheless limited by the inefficient utilization of reactive oxygen species (ROS). Herein, an erythrocyte membrane (EM)-modified core-shell upconversion nanoparticle (UCNP/Cur@EM) is designed and fabricated as a biomimetic nanobait to improve the PDT efficiency in AD. The UCNP with the outlayer of mesoporous silica is synthesized to load a high amount of the photosensitizer (curcumin), the unique optical feature of which can trigger curcumin to generate ROS upon near-infrared light (NIR) irradiation. Integration of EM enables the biomimetic nanobait to attract Aβ peptides trapped in the phospholipid bilayer, restraining the growth of Aβ monomers to form aggregates and improving the utilization rate of ROS to degrade the preformed Aβ aggregates. In vivo studies demonstrate that UCNP/Cur@EM irradiated by NIR enables to decrease Aβ deposits, ameliorates memory deficits, and rescues cognitive functions in the APP/PS1 transgenic mouse model. A biocompatible and controllable way is provided here to inhibit the amyloid protein-associated pathological process of AD.

Oil from Mullet Roe Byproducts: Effect of Oil Extraction Method on Human Erythrocytes and Platelets.

Background: The valorization of byproducts to obtain high nutritional value foods is of utmost importance for our planet where the population is booming. Among these products are oils rich in ω-3 fatty acids produced from fishery byproducts. Recently, mullet roe oil from roe byproducts was produced that was rich in the ω-3 fatty acids eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA). Oils are customarily characterized for their composition and degree of oxidation but little is known of their biological effects, especially the effect of the extraction method. Methods: The purpose of this study was to evaluate the effects of freshly extracted mullet roe oil from mullet roe byproducts and the effect of the extraction method on human red blood cells (hRBCs) and platelets. To this end, the hemocompatibility (cytotoxicity), oxidative effects, and erythrocyte membrane changes were examined after 1 and 24 h of incubation. Antiplatelet effects were also assessed in vitro. Results: The expeller press oil extraction method and alcalase-assisted extraction produced the most biocompatible oils, as shown by hemocompatibility measurements and the absence of erythrocyte membrane alterations. Solvent extracts and protease-assisted extraction oils resulted in the rupture of red blood cells at different examined dilutions, creating hemolysis. Conclusions: It seems that the proper functioning of oil-erythrocyte interactions cannot be explained solely by ROS. Further investigations combining chemical analysis with oil-cell interactions could be used as an input to design high nutritional value oils using green extraction technologies. All samples exhibited promising antiplatelet and antiblood clotting effects in vitro.

Alcohol-induced hormonal and metabolic alterations in plasma and erythrocytes—a gender-based study

Purpose This study aimed to understand the gender-specific alcohol-induced biochemical changes and TBARS association with the endocrine system. Methods Human male and female subjects ranging from 35 ± 10 years old with an 8-10-year drinking history were included in the study. Results The results demonstrated that testosterone levels were lower in male alcoholics and higher in female alcoholics, as well as higher estrogen and cortisol levels in both genders. In addition, we found lower T3, T4, and thyroid-stimulating hormone (TSH) levels in alcoholics of both sexes. Furthermore, plasma TBARS, protein carbonyls, nitrite, and nitrate levels increased significantly with concomitant decrease in reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in both male and female alcoholics. Furthermore, erythrocyte lysate nitrite and nitrate levels membrane total cholesterol, phospholipid and cholesterol/phospholipid (C/P) ratio with lower total membrane proteins in both genders of alcoholics. SDS-PAGE analysis of erythrocyte membrane proteins revealed increased density of band 3, protein 4.1, 4.2, 4.9 and glycophorins, whereas decreases in spectrin (α and β) were observed in both genders of alcoholics. Besides, alcoholics of both sexes had a lower ability to resist osmotic hemolysis. Plasma TBARS was negatively correlated with testosterone, TSH, T3 and T4 in male alcoholics, moreover, estradiol and cortisol were positively correlated in males and females respectively. Conclusion Female alcoholics may be more susceptible to osmotic hemolysis due to increased erythrocyte membrane lipid peroxidation with decreased antioxidant status, which results in an altered membrane C/P ratio and membrane protein composition.

Association between erythrocyte membrane fatty acids and gut bacteria in obesity-related cognitive dysfunction

Obesity increases the risk of cognitive impairment and dementia, and the gut microbiota can affect brain cognitive function and obesity through a variety of pathways such as the gut-brain axis. This study aimed to discover how fatty acid affect cognitive function by regulating intestinal flora in obesity. Obese subjects were recruited for cognitive function assessment, and participants were divided into obese group with cognitive impairment (MCI, n = 49) and obese cognitively normal group (Non_MCI, n = 55). In the erythrocyte membrane, the proportion of polyunsaturated fatty acids (PUFA), linoleic acid (C18:2 n-6) and arachidonic acid (C20:4 n-6) and n-6/n-3 ratio was higher in the MCI group than in the Non_MCI group. However, the α-linolenic acid (C18:3 n-3) percentage of the erythrocyte membrane was lower in the MCI group. We found that Coriobacteriales_Incertae_Sedis was positively correlated with erythrocyte membrane C20:4 n-6 and n-6 PUFA and negatively correlated with cognitive scores in obese patients. In addition, several of the functional pathways we predicted were significantly different in the MCI and Non_MCI groups. Higher levels of n-6/n-3 polyunsaturated fatty acids ratio in the erythrocyte membranes may influence the inflammatory response in the organism causing obesity induced cognitive damage. Moreover, high levels of n-6/n-3 polyunsaturated fatty acids ratio may also affect the intestinal flora of obese patients, which in turn may affect the cognitive function of obese patients.

Mechanical forces control the valency of the malaria adhesin VAR2CSA by exposing cryptic glycan binding sites.

Plasmodium falciparum (Pf) is responsible for the most lethal form of malaria. VAR2CSA is an adhesin protein expressed by this parasite at the membrane of infected erythrocytes for attachment to the placenta, leading to pregnancy-associated malaria. VAR2CSA is a large 355 kDa multidomain protein composed of nine extracellular domains, a transmembrane helix, and an intracellular domain. VAR2CSA binds to Chondroitin Sulphate A (CSA) of the proteoglycan matrix of the placenta. Shear flow, as the one occurring in blood, has been shown to enhance the (VAR2CSA-mediated) adhesion of Pf-infected erythrocytes on the CSA-matrix. However, the underlying molecular mechanism governing this enhancement has remained elusive. Here, we address this question by using equilibrium, force-probe, and docking-based molecular dynamics simulations. We subjected the VAR2CSA protein-CSA sugar complex to a force mimicking the tensile force exerted on this system due to the shear of the flowing blood. We show that upon this force exertion, VAR2CSA undergoes a large opening conformational transition before the CSA sugar chain dissociates from its main binding site. This preferential order of events is caused by the orientation of the molecule during elongation, as well as the strong electrostatic attraction of the sugar to the main protein binding site. Upon opening, two additional cryptic CSA binding sites get exposed and a functional dodecameric CSA molecule can be stably accommodated at these force-exposed positions. Thus, our results suggest that mechanical forces increase the avidity of VAR2CSA by turning it from a monovalent to a multivalent state. We propose this to be the molecular cause of the observed shear-enhanced adherence. Mechanical control of the valency of VAR2CSA is an intriguing hypothesis that can be tested experimentally and which is of relevance for the understanding of the malaria infection and for the development of anti placental-malaria vaccines targeting VAR2CSA.

Assessment of variations in the haematological and hepatorenal biomarkers alongside oxidant‐antioxidant imbalance in exotic and indigenous horses infected with Theileria equi

SummaryBackgroundTheileria equi latently infected horses remain under oxidative stress which can be easily determined by evaluating the concerned biomarkers. Until now, very limited data are available regarding study of oxidative stress alongside hepatorenal biomarker alterations in carrier equids.ObjectivesThis study was aimed to investigate oxidative stress and hepato‐renal alterations in respective biomarkers in latently T. equi‐infected exotic and indigenous horses.Study designThe study involved 24 (n = 24) T. equi latently infected horses (11 exotic and 13 indigenous) while 50 horses (n = 50) served as the non‐infected group. Haematological, hepato‐renal and oxidative stress biomarkers analysis was carried out to evaluate the effect of latent T. equi infection on these parameters.ResultsIn the T. equi‐infected exotic horse group, significant decreases in Hb, PCV, TLC and eosinophils were observed in comparison with the T. equi‐infected indigenous horse group. Blood glucose and SOD levels were significantly lower while serum MDA levels were significantly increased in T. equi‐infected horses than the noninfected groups. Higher MDA levels are suggestive of biochemical changes in parasitised erythrocytes making their membrane rigid and liable to erythrolysis. Decreased SOD levels were indicative of a disturbance in anti‐oxidative mechanisms leading to accumulation of free radicals attributing to oxidative injuries to T. equi‐infected erythrocytes.Main limitationsLatently infected animals with very low parasitaemia which are unable to damage host cells may lead to false negative results. Another limitation is the difficulty in ruling out other similar disease‐causing oxidative stresses.ConclusionThese observations indicated that T. equi naturally latently infected exotic horses were more liable to develop a condition in comparison to indigenous infected horses. From the above results, we can conclude that T. equi infection exerts a marked effect on the hepato‐renal biomarkers and significantly affects the key antioxidant defence mechanisms of infected erythrocytes, leading to oxidative damage to the erythrocytes membrane and ultimately its haemolysis.

Sex differences in erythrocyte fatty acid composition of first-diagnosed, drug-naïve patients with major depressive disorders.

Background: Since depression, sex hormones, and fatty acid status are interrelated, it is important to understand their relationships. In this study, we aimed to investigate sex differences in erythrocyte membrane fatty acid composition among first-diagnosed, drug-naïve patients with major depressive disorders. Methods: The study included 139 individuals with first-diagnosed, drug-naïve depression (male/female = 48/91) and 55 healthy controls (male/female = 24/31). The levels of erythrocyte membrane fatty acids were analyzed to compare the difference between males and females in both patients with depression and healthy controls, as well as to study their correlation with depressive symptoms. Results: In first-diagnosed, drug-naïve patients with major depressive disorders, sex disparities were observed in the levels of erythrocyte saturated fatty acids (SFAs) and n-6 PUFAs (such as C18:0, C20:4n6 and C22:4n6), where higher levels evident in females compared to in males. We found a noteworthy correlation between fatty acid levels and depressive symptoms, in which there is a significant association between female patients and depression but a weaker association between male patients and depression. Conclusion: Our findings demonstrate higher levels of n-6 PUFAs and SFAs in female patients with depression. The relationship between fatty acid composition and depressive symptoms was more prominent in females than males. These findings highlight the significance of considering sex as a crucial and interconnected factor in future investigations and potential adjunctive treatment for mood disorders by targeting fatty acid metabolism.

Ultrasound-Stimulated "Exocytosis" by Cell-Like Microbubbles Enhances Antibacterial Species Penetration and Immune Activation Against Implant Infection.

Host immune systems serving as crucial defense lines are vital resisting mechanisms against biofilm-associated implant infections. Nevertheless, biofilms hinder the penetration of anti-bacterial species, inhibit phagocytosis of immune cells, and frustrate host inflammatory responses, ultimately resulting in the weakness of the host immune system for biofilm elimination. Herein, a cell-like construct is developed through encapsulation of erythrocyte membrane fragments on the surface of Fe3 O4 nanoparticle-fabricated microbubbles and then loaded with hydroxyurea (EMB-Hu). Under ultrasound (US) stimulation, EMB-Hu undergoes a stable oscillation manner to act in an "exocytosis" mechanism for disrupting biofilm, releasing agents, and enhancing penetration of catalytically generated anti-bacterial species within biofilms. Additionally, the US-stimulated "exocytosis" by EMB-Hu can activate pro-inflammatory macrophage polarization and enhance macrophage phagocytosis for clearance of disrupted biofilms. Collectively, this work has exhibited cell-like microbubbles with US-stimulated "exocytosis" mechanisms to overcome the biofilm barrier and signal macrophages for inflammatory activation, finally achieving favorable therapeutic effects against implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms.

Using Mesoporous Silica-Based Dual Biomimetic Nano-Erythrocytes for an Improved Antitumor Effect.

The nano-delivery system with a dual biomimetic effect can penetrate deeper in tumor microenvironments (TMEs) and release sufficient antitumor drugs, which has attracted much attention. In this study, we synthesized erythrocyte-like mesoporous silica nanoparticles (EMSNs) as the core loaded with doxorubicin (DOX) and coated them with calcium phosphate (CaP) and erythrocyte membrane (EM) to obtain DOX/EsPMs. The transmission electron microscopy (TEM), fluorescent co-localization and protein bands of SDS-PAGE were used to confirm the complete fabrication of EsPMs. The EsPMs with erythrocyte-like shape exhibited superior penetration ability in in vitro diffusion and tumor-sphere penetration experiments. Intracellular Ca2+ and ROS detection experiments showed that the CaP membranes of EsPMs with pH-sensitivity could provide Ca2+ continuously to induce reactive oxide species' (ROS) generation in the TME. The EM as a perfect "camouflaged clothing" which could confuse macrophagocytes into prolonging blood circulation. Hemolysis and non-specific protein adsorption tests proved the desirable biocompatibility of EsPMs. An in vivo pharmacodynamics evaluation showed that the DOX/EsPMs group had a satisfactory tumor-inhibition effect. These advantages of the nano-erythrocytes suggest that by modifying the existing materials to construct a nano-delivery system, nanoparticles will achieve a biomimetic effect from both their structure and function with a facilitated and sufficient drug release profile, which is of great significance for antitumor therapy.

Atherogenic features of the fatty acid profile of erythrocyte membranes of patients with fatty liver disease of mixed genesis

Aim of the study was to investigate the features of the fatty acid (FA) profile of erythrocyte membranes of patients with fatty liver disease (FLD) of mixed genesis (metabolic + alcoholic) from the point of view of atherogenic changes.Material and methods. 31 men (50.6 ± 9.9 years old) with FLD of mixed genesis, the degree of liver fibrosis corresponded to 0-1 (FibroScan ® 502 Echosens, France), and 28 persons of the comparison group, comparable in age, were examined. The study of the composition of FAs of erythrocyte membranes was carried out using gas chromatography/mass spectrometry – a system based on three quadrupoles Agilent 7000B (USA).Results. Patients with FLD of mixed genesis had higher level of palmitoleic (p = 0.03), pentadecanoic (p = 0.05), omega-6 to omega-3 polyunsaturated fatter acids (PUFA) ratio (p = 0.03) and, conversely, lower level of docosahexaenoic (p = 0.0002), total content of eicosapentaenoic and docosahexaenoic FA (p = 0.0007), of all omega-3 PUFA (p = 0.001) in the membranes of erythrocytes compared to healthy persons. There are trends towards a decrease in the content of omega-3 eicosapentaenoic acid and an increase in the ratio of SFA/PUFA in patients with fibroids of mixed genesis in contrast to healthy individuals. The level of individual FA provided high diagnostic accuracy in differentiating patients with FLD of mixed genesis from healthy individuals: palmitoleic (9-C16:1) (area under ROC (AUC) 0.702, sensitivity 66.7 %, specificity 69.6 %), docosahexaenoic (C22:6n-3) (AUC 0.795, sensitivity 77.3 %, specificity 78.3 %), as well as the total content of eicosapentaenoic and docosegexaenoic FA (C20:5n-3 + C22:6n-3) (AUC 0.777, sensitivity 70.1 %, specificity 82.6 %).Conclusions. The revealed features of the profile of erythrocyte membrane FA in FLD of mixed genesis – increase of saturated, monounsaturated, omega-6 PUFA content and reduce of omega-3 PUFA concentration are atherogenic. The continuation of research in terms of the use of FAs as biomarkers of this pathology and targets for therapeutic effects should be considered promising.

Effect of age and dietary habits on Red Blood Cell membrane fatty acids in a Southern Europe population (Basque Country)

The levels of blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are very variable and, in general, low in most of the world population. In this study, the effects of age, sex, COVID-19, and dietary habits on the lipid profile of the erythrocyte membranes were assessed in a sub-cohort of healthy population (N = 203) from a large cohort of individuals from the Basque Country, Spain, (AKRIBEA). Sex did not have an effect on RBC lipid profile. COVID-19 infected participants showed higher levels of DGLA. Oldest participants showed higher oleic acid, EPA and DHA levels. Arachidonic acid in RBC correlated positively with the intake of sunflower oil, butter, eggs, processed and red meat, whereas DHA and EPA correlated positively with oily and lean fish. Basque Country population showed lipid profiles similar to other high fish consuming countries, such as Italy and Japan. Baseline levels of the whole lipidomic profile of the RBC including SFA, MUFA and PUFA should be examined to obtain a better description of the health and nutritional status.

Profiles of global mutations in the human intercellular adhesion molecule-1 (ICAM-1) shed light on population-specific malaria susceptibility

Plasmodium falciparum is responsible for malaria-related morbidity and mortality. PfEMP1 (P. falciparum erythrocyte membrane protein 1) mediates infected erythrocytes adhesion to various surface vascular receptors, including intercellular adhesion molecule-1 (ICAM-1), associating this interaction with severe malaria in several studies. Genetic variation in host ICAM-1 plays a significant role in determining susceptibility to malaria infection via clinical phenotypes such as the ICAM-1Kilifi variant which has been reported to be associated with susceptibility in populations. Our genomic and structural analysis of single nucleotide polymorphisms (SNPs) in ICAM-1 revealed 9 unique mutations each in its distinct A-type and BC-type PfEMP1 DBLβ-interacting regions. These mutations are noted in only a few field isolates and mainly in the African/African American population. The ICAM-1Kilifi variant lies in a flexible loop proximal to the DBLβ-interacting region. This analysis will assist in establishing functional correlations of reported global mutations via experimental and clinical studies and in the tailored design of population-specific genetic surveillance studies. Understanding host polymorphism as an evolutionary force in diverse populations can help to predict predisposition to disease severity and will contribute towards laying the framework for designing population-specific personalized medicines for severe malaria.

DISORDERS OF THE FATTY ACID SPECTRUM OF ERYTHROCYTES AND BLOOD PLASMA OF ADOLESCENTS WITH RECURRENT CEPHALGIA ASSOCIATED WITH HYPERTENSION. APPROACHES TO CORRECTION

The spectrum of fatty acids (FA) in erythrocytes and blood plasma reflects the characteristics of lipid metabolism in diseases of vascular origin, including cephalalgia associated with arterial hypertension (AH). Timely diagnosis and correction of violations of this spectrum is important for the prevention of diseases of the cardiovascular and nervous system in subsequent age periods of life. Objective. To study the characteristics of the FA spectrum of erythrocyte membranes and blood plasma in adolescents with recurrent cephalalgia associated with AH. Material and methods. The composition of FA of erythrocytes and blood plasma was studied in 51 adolescents aged 12–18 years with recurrent cephalgia associated with AH and without AH. Determination of the FA composition of erythrocytes and blood plasma was carried out by gas-liquid chromatography-mass spectrometry with preliminary lipid extraction according to the Folch method. The analysis of FA methyl esters was carried out on a gas chromatograph with a GCD Plus mass spectrometric detector (Hewlett-Packard, USA). Results. The features of the structural redistribution of individual FA in adolescents with cephalgia and AH in the form of a predominance of saturated and monoenic FA in erythrocytes with a simultaneous decrease in their content in blood plasma, as well as a tendency to a decrease in the concentration of polyunsaturated FA in erythrocytes and their increase in plasma. Conclusion. Early detection and timely correction of disorders of the FA spectrum of erythrocyte membranes and blood plasma is necessary, starting from childhood and adolescence, in order to subsequently reduce the risk of developing diseases of the cardiovascular and nervous system associated with these disorders.

Enhancing Bone Regeneration through CDC20-Loaded ZIF-8 Nanoparticles Wrapped in Erythrocyte Membranes with Targeting Aptamer.

In the context of bone regeneration, nanoparticles harboring osteogenic factors have emerged as pivotal agents for modulating the differentiation fate of stem cells. However, persistent challenges surrounding biocompatibility, loading efficiency, and precise targeting ability warrant innovative solution. In this study, a novel nanoparticle platform founded upon the zeolitic imidazolate framework-8 (ZIF-8) is introduced. This new design, CDC20@ZIF-8@eM-Apt, involves the envelopment of ZIF-8 within an erythrocyte membrane (eM) cloak, and is coupled with a targeting aptamer. ZIF-8, distinguished by its porosity, biocompatibility, and robust cargo transport capabilities, constitutes the core framework. Cell division cycle protein 20 homolog (CDC20) is illuminated as a new target in bone regeneration. The eM plays a dual role in maintaining nanoparticle stability and facilitating fusion with target cell membranes, while the aptamer orchestrates the specific recruitment of bone marrow mesenchymal stem cells (BMSCs) within bone defect sites. Significantly, CDC20@ZIF-8@eM-Apt amplifies osteogenic differentiation of BMSCs via the inhibition of NF-κB p65, and concurrently catalyzes bone regeneration in two bone defect models. Consequently, CDC20@ZIF-8@eM-Apt introduces a pioneering strategy for tackling bone defects and associated maladies, opening novel avenues in therapeutic intervention.

10-Hydroxydec-2-enoic acid enhances the erythrocyte membrane fluidity via interacting with phosphatidylcholine and phosphatidylethanolamine

10-Hydroxydec-2-enoic acid (10-HDA), the unique substance in the natural food royal jelly, is an unsaturated hydroxyl fatty acid with the bio-activity to guard against cell or tissue damages. However, the relevant mechanisms still remain largely unknown. Here, using a mouse erythrocyte model, whether the fluidity of plasma membrane is influenced by 10-HDA was investigated. 10-HDA was shown to enhance the erythrocyte membrane fluidity and to rescue the fluidity from •OH toxicity. In such occasions, 10-HDA promoted the dissolved O2 level in erythrocyte suspension thereof. The levels of β-actin and band 4.1 protein were not affected by 10-HDA in erythrocytes. In the framework of density functional theory, 10-HDA may interact with phosphatidylcholine and phosphatidylethanolamine, the major components of membrane lipid bilayer. This was evidenced by the fact that 10-HDA was detectable in erythrocytes after its addition to the erythrocyte suspension. Moreover, the fluorescent intensity of erythrocytes stained by the membrane probe DiIC18(5) increased with 10-HDA treatment. Hence, 10-HDA could regulate the erythrocyte membrane fluidity and the release of O2 from erythrocytes via targeting lipids rather than proteins. Our data cast light on the elucidation of the mechanism of 10-HDA modulating cell functionality and the utilization of 10-HDA in remedying the erythrocyte membrane fluidity-associated symptoms.

SPECTROPHOTO AND DIGITAL COLORIMETRIC DETERMINATION INDICATOR OF BETA-ADRENOREACTIVITY OF ERYTHROCYTE MEMBRANES OF PATIENTS WITH BRONCHIAL ASTHMA

The change in the adrenoreactive properties of membrane and cellular structures under the influence of catecholamines makes it possible to consider the beta-adrenergic reactivity of the erythrocyte membrane (-ARM) as a systemic indicator of the organism's adrenoreactivity. To assess adrenoreactivity, a technique is used based on a quantitative assessment of the degree of inhibition of hypoosmotic hemolysis of erythrocytes in vitro in the presence of the beta-blocker propranolol. The article presents data on the comparison of spectrophoto- and colorimetric determination of erythrocyte membrane beta-adrenoreactivity based on the registration of erythrocyte hemolysis with digital signal processing. A smartphone was used to register the images of the analyzed samples. Photography was carried out in a special box under standard lighting conditions. The chromaticity of the obtained images was evaluated using the Photoshop program within the RGB color model intended for computer color rendering. The obtained RGB values were used for quantitative determinations. The study was performed on 20 blood samples of patients suffering from bronchial asthma. The discrepancy between the results of determining -ARM using the colorimetric and spetrophotometric methods was no more than 5.6%, which indicates the possibility of replacing the spectrophotometer with image registration in digital format using software.

In silico analysis of putative hemolysin proteins in the genome of Vibrio alginolyticus ATCC 17749 and their structure prediction

Hemolysin is one of the major pathogenic factors for pathogenic bacteria. Hemolysin can break down erythrocytes (RBC) which is called hemolysis. Hemolysins act on the cell membrane of erythrocytes, resulting in pore formation in the membrane and liberating hemoglobin into the growing environment. Hemoglobin is used as an iron source by pathogenic bacteria with the help of a siderophore or is taken up via iron receptors present on the bacterial cell membrane. Despite the pore formation into erythrocytes, hemolysin or cytolysin has also the ability to pore formation in a broad range of the cells such as mast cells, neutrophils and polymorphonuclear cells. It also enhances virulence by causing tissue and cell damage. Hemolysin is associated with the pathogenesis of different Vibrio spp. that cause either wound infection or intestinal infection. V. cholerae and V. parahemolyticus are popularly known for intestinal infection whereas V. alginolyticus and V. vulnificus cause would infections. The genome of Vibrio alginolyticus ATCC 17749 was analyzed for the gene responsible for the biosynthesis of hemolysins. Its genome encodes for five hemolysins that might play an important role in hemolysis and pathogenesis. Physiological properties functional annotation and predicted structure will significantly increase the level of understanding of hemolysins of Vibrio alginolyticus ATCC 117749.