Erythrocyte Aggregation Research Articles

Glycocalyx cleavage boosts erythrocytes aggregation

The glycocalyx is a complex layer of carbohydrate and protein molecules that surrounds the cell membrane of many types of mammalian cells. It serves several important functions, including cell adhesion and communication, and maintain cell shape and stability, especially in the case of erythrocytes. Alteration of glycocalyx composition represents a cardiovascular health threatening. For example, in diabetes mellitus glycocalyx of erythrocytes and of endothelial cells is known to be impaired, a potential source of blood occlusion in microcirculation, which may lead to blindness, and renal failure of patients. The impact of glycocalyx impairment on erythrocyte aggregation remains a largely unexplored research area. We conduct here in vitro-experiments in microfluidic devices in order to investigate erythrocytes aggregation incubated with amylase, an enzyme that partially breaks down glycocalyx molecules. It is found that incubation of erythrocytes by amylase leads to a dramatic increase of their aggregation and stability and alters the aggregates morphologies. Confocal microscopy analysis reveals a significant degradation of the glycocalyx layer, correlated with enhanced erythrocytes aggregation. An increased erythrocyte aggregation in vivo should affect oxygen and other metabolites delivery to organs and tissues. This study brings new elements about elucidation of microscopic origins of erythrocyte aggregation and their potential impact on cardiovascular pathologies.

Comprehensive Analysis of Sulfated Flavonoids in Eclipta prostrata for Quality Evaluation

Eclipta prostrata (Asteraceae) is employed as a hemostatic agent in many traditional medicines, owing to its sulfated flavonoid content. In this study, we obtained crude drug samples from three provinces collected in different years and analyzed their sulfated flavonoid contents using liquid chromatography–mass spectrometry (LC–MS) for quality evaluation. Because sulfated flavonoids are unstable and difficult to isolate from extracts, this study first synthesized a variety of sulfated flavonoids and accumulated spectral data in order to identify the compounds in E. prostrata. The LC–MS analysis of six crude drug samples revealed the presence of luteolin 7-sulfate, apigenin 7-sulfate, diosmetin 7-sulfate, and diosmetin 3′-sulfate. The samples without luteolin 3′-sulfate featured high apigenin 7-sulfate content. Although the samples were collected from the same locality, their compositions differed depending on the year of collection. Further, they were classified according to three patterns: (1) samples with luteolin 7-sulfate as the main component, (2) samples with apigenin 7-sulfate as the main component, and (3) samples with relatively high diosmetin sulfate content. Luteolin 7-sulfate typically exhibits relatively high erythrocyte aggregation efficiency and fibrinogen aggregation rate. These results demonstrate that the analysis of sulfated flavonoids is beneficial for the quality evaluation of E. prostrata for hemostatic applications.

Investigation of Hemorheological Parameters in Ischemic Stroke Patients.

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

Simultaneous influences of hematocrit in the erythrocyte medium on erythrocyte aggregation and sedimentation: a kinetic study by a laser scattering technique

The erythrocyte aggregation is an important physiological phenomenon in the circulation of blood. It is a basic characteristic of normal blood that plays a major role in the cardiovascular system, especially in the microcirculation. This study explained the kinetics of single cells rouleaux formation one- dimensional aggregate and three- dimensional aggregate, during simultaneous, and the effect of hematocrit on the process of aggregation and sedimentation. The present study was done on forty one healthy subjects. Laser light is passed through a well mixed sample of blood and the forward scattered light intensities recorded continuously. The samples were prepared with different hematocrit, (10%, 15%, 20%, and 25%). Increasing the hematocrit, (10%, 15%, 20%, and 25%) had significantly decreased the rate of rouleaux formation (P< 0.005) but increase in the rate of one and three dimensional aggregate formation. On the other hand the sedimentation rate is decreased significantly (P

Features of the immune system and levels of blood transport components in residents of the arctic of the Russian Federation.

The peripheral venous blood of 191 residents of the Arctic of the Russian Federation (Murmansk Oblast) aged 21-55 analyzed comprehensively. Blood was sampled from the ulnar vein on an empty stomach in the morning. The hemogram, phagocytic activity of neutrophils, lymphocyte content with CD3, CD4, CD8, CD10, CD19, CD16, CD71, CD25, HLA-DR and CD95 phenotypes, concentrations of cytokines: TNF-α, IFN-γ, IL-6, IL-10, extracellular receptor pool: sCD71, sCD62L, sApo-1/Fas, sFasL, circulating immune complexes (CIC) and blood transport components: haptoglobin (Hp), transferrin, IgM, IgG, IgA, IgE (immunoglobulins M, G, A and E) low-density lipoproteins (LDL), and high density lipoprotein (HDL) were evaluated. The results were analyzed using descriptive statistics and comparative, factorial, and regression analyses. Residents of the Murmansk Oblast exhibit a high prevalence of erythrocytosis (62.3%), thrombocytosis (25.0%), leukocytosis (20.1%), and increased hemoglobin (Hb) concentrations (42.5%), coupled with a significantly decreased level of active phagocytes (47.6%). A significantly decreased level of lymphocytes with phenotypes CD3 (92.4%), CD4 (40.4%), CD71 (62.3%) was revealed, coupled with the activation of lymphocytes with phenotypes CD16 (50.1%), CD8 (37.5%), CD19 (15.9%) and increased concentrations of pro-inflammatory IFN-γ (47.9%), IL-6 (33.3%), and TNF-α (20.1%). Elevated levels of sCD71 (56.6%), sCD62L (32.1%), sApo-1/Fas (22.1%), sFasL (10.2%), and autoantibodies to double-stranded DNA (57.1%), RNA (10.4%), and oLDL (oxidized-modified LDL) (16.3%) were recorded in residents of the Murmansk Oblast. Arctic residents showed elevated concentrations of Hp (63.3%), IgM (63.9%), IgA (42.4%), IgE (18.8%), LDL (24.9%), and a decreased level of HDL (21.1%) owing to an ApoA-I ligand deficiency (58.1%). Elevated levels of Hp in the blood are associated with increased erythrocyte aggregation frequency, T-lymphocyte activation, and increased concentration of free receptors of the extracellular pool. Increased IgM and IgA levels in the blood are attributed to the need to bind components of the extracellular receptor pool sCD71, sCD62L, sApo-1/Fas, sFasL and are associated with decreased levels lymphocyte with CD8 and CD16 phenotypes. The humoral immune response in Arctic residents is triggered when the cellular component of immunity is under strain which compounded by ineffective clearance of metabolic byproducts owing to imbalanced LDL and HDL lipid transport complexes. The immune system of Arctic residents is characterized by excessive cytotoxic activity of lymphocytes and increased concentrations of pro-inflammatory cytokines, free forms of receptors of the extracellular pool, and autoantibodies. The change in the content of transport components of the blood system is directed at maintaining homeostasis by exhibiting antioxidant, anti-inflammatory, and immunoregulatory properties.

Buyang Huanwu decoction promotes angiogenesis and improves hemorheological parameters after cervical spinal cord injury

ObjectiveTo explore the effects of Buyang Huanwu decoction (BYHWD) on vascular neogenesis and hemorheological parameters following cervical spinal cord injury (SCI). MethodsAn acute cervical SCI model was established using 84 female Sprague–Dawley rats. Functional recovery of the rats was evaluated using the forelimb locomotor scale score, forelimb grip strength test, and Basso-Beattie-Bresnahan score. The animals were subsequently euthanized at days 7 and 28 postoperatively. The gross morphology, neuronal survival, and myelin sheath in the injured area were evaluated using hematoxylin and eosin (HE), Nissl, and luxol fast blue (LFB) staining, respectively. Immunofluorescence staining was used to observe CD31 expression 7 days post-injury. Furthermore, the expression of CD31, neuronal nuclear protein (NeuN), and myelin basic protein (MBP) were evaluated 28 days post-injury. Additionally, vascular endothelial growth factor A (VEGFA) and VEGF receptor-2 (VEGFR-2) expression was evaluated using western blotting. Whole-blood viscosity, plasma viscosity, and red blood cell aggregation were measured using a hemorheometer. ResultsFrom postoperative days 3–28, motor function in the BYHWD group began to recover considerably compared to the SCI group. BYHWD effectively restored spinal cord histopathology. In addition, the number of NeuN-positive cells, and fluorescence intensity of CD31at 7 and 28 days and MBP significantly increased in the BYHWD group compared with the SCI group (all P < 0.05). Moreover, this decoction significantly upregulated the expression of VEGFA and VEGFR-2 (all P < 0.05). BYHWD improved the hemorheology results (i.e., except erythrocyte aggregation index in the low-dose group), revealing statistically significant differences compared with the SCI group (all P < 0.05). ConclusionBYHWD effectively promoted angiogenesis, improved hemorheological parameters, and protected neurons and myelin sheaths, ultimately promoting the recovery of neurological function after cervical SCI in rats. These findings suggest that BYHWD promotes vascular neogenesis through the VEGFA/VEGFR-2 pathway.

Application of buried auricular point combined with Wenjing Sanhan prescription in arteriosclerosis obliterans patients with resting pain.

Research on the combined use of ear acupoint embedding beans and warming meridians with cold-dispersing formulas for alleviating resting pain in patients with arteriosclerosis obliterans (ASO) remains limited. To explore the therapeutic efficacy of auricular point embedding beans combined with Wenjing Sanhan prescription in alleviating resting pain in patients with lower-limb ASO. A total of 100 patients with ASO experiencing resting pain who were treated at our hospital from January 2022 to January 2023 were enrolled. They were randomly allocated into two groups using a double-blind approach. The control group was treated using a warming meridian with a cold-dispersing formula, while the study group received additional treatment with ear acupoint embedding beans. The clinical efficacy, ankle-brachial artery pressure ratio, hemorheological indicators, and traditional Chinese medicine symptom scores were compared between the two groups. The clinical efficacy rate in the study group was significantly higher (94.00%) than that in the control group (72.00%, P < 0.05). Moreover, the ankle-brachial artery pressure ratio was significantly higher in the study group after treatment (P < 0.05). Hemorheological parameters, including whole blood viscosity, plasma viscosity (1.83 ± 0.11) mPa/s, fibrinogen levels (3.30 ± 0.21) g/L, platelet adhesion rate (49.87% ± 10.51%), and erythrocyte aggregation index (1.79 ± 0) were improved in the study group compared to the control group. In addition, the scores for decreased skin temperature (1.41 ± 0.26), intermittent claudication (1.30 ± 0.20), and resting pain (1.23 ± 0.31) were significantly lower in the study group than those in the control group (all P < 0.05). The level of oxidative stress in the study group also exhibited significant improvement (P < 0.05), and the levels of inflammatory factors were considerably lower than those in the control group. The combination of ear point embedding beans and Wenjing Sanhan prescription demonstrates promising clinical efficacy in alleviating resting pain associated with ASO.

Relationship between Capillaroscopic Architectural Patterns and Different Variant Subgroups in Fabry Disease: Analysis of Cases from a Multidisciplinary Center.

Anderson-Fabry disease (AFD) is a genetic lysosomal storage disorder caused by mutations in the α-galactosidase A gene, leading to impaired lysosomal function and resulting in both macrovascular and microvascular alterations. AFD patients often exhibit increased intima-media thickness (IMT) and reduced flow-mediated dilation (FMD), indicating non-atherosclerotic arterial thickening and the potential for cardiovascular events. Nailfold capillaroscopy, a non-invasive diagnostic tool, has shown potential in diagnosing and monitoring microcirculatory disorders in AFD, despite limited research. This study evaluates nailfold capillaroscopy findings in AFD patients, exploring correlations with GLA gene variant subgroups (associated with classical or late-onset phenotypes and variants of uncertain significance (VUSs)), and assessing morpho-functional differences between sexes. It aims to determine whether capillaroscopy can assist in the early identification of individuals with multiorgan vascular involvement. A retrospective observational study was conducted with 25 AFD patients from AOUP "G. Rodolico-San Marco" in Catania (2020-2023). Patients underwent genetic testing, enzyme activity evaluation, and nailfold capillaroscopy using Horus basic HS 200 videodermatoscopy. Parameters like angiotectonic disorder, vascular areas, capillary density, and intimal thickening were assessed. The study identified significant differences in capillaroscopy findings among patients with different GLA gene variant subgroups. Classic AFD variant patients showed reduced capillary length and signs of erythrocyte aggregation and dilated subpapillary plexus. No correlation was found between enzymatic activity and capillaroscopy parameters. However, Lyso-Gb3 levels were positively correlated with average capillary length (ῤ = 0.453; p = 0.059). Sex-specific differences in capillaroscopy findings were observed in neoangiogenesis and average capillary length, with distinct implications for men and women. This study highlights the potential of nailfold capillaroscopy in the diagnostic process and clinical management of AFD, particularly in relation to specific GLA gene mutations, as a valuable tool for the early diagnosis and monitoring of AFD.

Erythrocyte-Mimicking Nanovesicle Targeting Porphyromonas gingivalis for Periodontitis.

Porphyromonas gingivalis has been demonstrated to have the strongest association with periodontitis. Within the host, P. gingivalis relies on acquiring iron and heme through the aggregation and lysis of erythrocytes, which are important factors in the growth and virulence of P. gingivalis. Additionally, the excess obtained heme is deposited on the surface of P. gingivalis, protecting the cells from oxidative damage. Based on these biological properties of the interaction between P. gingivalis and erythrocytes, this study developed an erythrocyte membrane nanovesicle loaded with gallium porphyrins to mimic erythrocytes. The nanovesicle can target and adhere with P. gingivalis precisely, being lysed and utilized by P. gingivalis as erythrocytes. Ingested gallium porphyrin replaces iron porphyrin in P. gingivalis, causing intracellular metabolic disruption. Deposited porphyrin generates a large amount of reactive oxygen species (ROS) under blue light, causing oxidative damage, and its lethality is enhanced by bacterial metabolic disruption, synergistically killing P. gingivalis. Our results demonstrate that this strategy can target and inhibit P. gingivalis, reduce its invasion of epithelial cells, and alleviate the progression of periodontitis.

Evaluation of the Phytochemical Screening of Methanolic Seed Extracts of Tribulus terrestris: An In Vitro Application of Anti-cancer, Anti-oxidant, and Anti-microbial Activities.

Tribulus terrestris, a plant known for its pharmacological properties, was investigated in this study for its potential anticancer effects against oral cancer cells. The study aimed to explore the phytochemical composition of T. terrestris seed extract and evaluate its cytotoxic, pro-apoptotic, antioxidant, anti-inflammatory, and antimicrobial activities. Methanolic seed extracts of T. terrestris were obtained and subjected to phytochemical analysis to identify bioactive compounds. The cytotoxic effect of the extract on oral cancer cells was evaluated using the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide)assay, while pro-apoptotic effects were assessed through dual fluorescent staining. Antioxidant activity was measured using hydrogen peroxide and erythrocyte aggregation assays, while anti-inflammatory activity was evaluated through inhibition of albumin denaturation. Phytochemical analysis revealed the presence of alkaloids, tannins, saponins, flavonoids, and phenols in T. terrestris seed extract. The extract demonstrated concentration-dependent cytotoxicity against oral cancer cells, with 100 μg/mL showing significant growth inhibition. Pro-apoptotic effects were observed, with characteristic morphological changes in cancer cells treated with the extract. Antioxidant activity was demonstrated by the extract, with methanol fraction of a flower (MFF) exhibiting the highest capacity, followed by total trichome fraction (TTF), and a positive correlation between phenolic content and free radical scavenging effectiveness was noted. Antimicrobial activity against various pathogens, including bacteria and fungi, was also observed, with higher concentrations showing increased efficacy. The study concludes that methanolic extracts of T. terrestris possess significant anticancer, antioxidant, anti-inflammatory, and antimicrobial activities. These findings highlight the potential of T. terrestris as a candidate for further research and clinical applications, either alone or in combination with other agents, for the treatment of oral cancer and associated conditions.

Effect of Vitamin K2 on Blood Rheology and Vascular Responses in Diabetic Rats

Background/aim: Diabetes is manifested by endothelial dysfunction and an imbalance between vasoconstriction and vasodilation. The aim of our study is to examine the effect of vitK2 application on vascular and rheological parameters in a rat diabetes model. Materials and methods: A total of 60 male Wistar Albino rats were used to examine vascular responses and hemorheological parameters. A total of 6 groups were: control (C), control+vehicle (Cv), control+vitK2 administered (C + K2), diabetes (D), diabetes+vehicle (Dv), and diabetes+vitK2 (D + K2) group. After the animals were sacrificed, blood and vascular samples were taken and the contraction and relaxation responses of the aorta and erythrocyte deformability and aggregation were examined. Results: When KCl dose-response curves are evaluated; Increased vasoconstriction response was found in the Dv group compared to the Cv group. The increase in vasoconstriction observed in the Dv group decreased with the application of vit K2. D+vitK2 group thoracic aorta contraction responses returned to Cv group levels. In response to increasing cumulative doses of Phe, a significant increase in vasoconstriction response was observed in the Dv group compared to the Cv group. VitK2 application reduced the Phe-mediated contractile response, which was increased in the Dv group, and returned the contraction response to Cv conditions except for two intermediate Phe doses. In the Dv + K2 group, a significant decrease was observed in the aggregation index, which was tended to increase. Conclusion: Considering the cardiovascular complications frequently observed in diabetes, it can be suggested that vitK2 therapy may yield positive outcomes in diabetes.

High fibrinogen content in pregnant women – pathology or overdiagnosis?

An increased fibrinogen (FG) concentration during pregnancy is considered a protective mechanism against bleeding during childbirth. An enlarged amount of FG increases the aggregation of erythrocytes, blood plasma viscosity, microvascular resistance – permanent elements of the pathogenesis of arterial hypertension, stroke, coronary heart disease. It is also associated with an increased likelihood of development of preeclampsia and stroke with subsequent neurological disorders.In addition to its undeniable importance for hemostasis, FG is directly related to several physiological and pathophysiological conditions, such as infection, wound healing, tumorigenesis, and the severity of atherosclerosis. It also has a decisive role in the development of pregnancy. Maternal FG is necessary for the progress of pregnancy, as it stabilizes the utero-placental connection at the fibrinoid layer of the fetal-maternal junction. No reports on the study of pathological forms of FG in Ukraine were found.The objective: to compare the indicators of FG concentration and related elements of the blood coagulation system of pregnant and parturient women in different gestational periods and after childbirth.Materials and methods. Blood components from the ulnar vein of 30 women in labor at a gestation period of 22–27 weeks (extremely preterm birth (EPB) – I group), 37 women in labor at a term of 28–34 weeks (early preterm birth (PB) – II group) and 40 women with gestational period 37–41 weeks (control group (CG) – III group) was studied. In the collected samples the content of FG, D-dimer (Dd), prothrombin index (PI), activated partial thromboplastin time (APTT), as well as the levels of hemoglobin (Hb), hematocrit (Ht) and total protein (TP) of the blood plasma were determined.All women in labor were hospitalized in the active phase of the I labor period and did not receive infusion therapy. In terms of gestation, corresponding to EPB, early PB and CG, 10 pregnant women who were on outpatient registration at the Perinatal Center were examined for comparison of the studied indicators outside of labor.Indicators of the biochemical coagulogram were studied on a Helena C-2 semi-automatic coagulometer (Helena Biosciences, Great Britain).Results. The FG concentration increased from 4.2±0.56 g/l in the term 22–27 weeks to 4.4±0.57 g/l before delivery with a diapason of 3.5 to 5.0 g/l. In all parturients, the FG concentration was lower than 4.5 g/l, respectively by group: 4.5±0.81; 4.1±0.74 and 4.1±0.65 g/l (р&lt;0.05). In 24 hours after delivery the FG concentration increased in CG to 5.0±0.82 g/l, and after 48 hours – to 5.3±1.19 g/l, which exceeded the indicators of parturients of the EPB and early PB groups and pregnant women of these same terms, in which the highest indicator was 4.5±0.81 g/l in the EPB group (p&lt;0.05).An increase in the Dd index with growing gestational age was observed in all pregnant women (from 274±133.3 to 501±174.7 μg/l). It continued during the first postpartum day – up to 685±157.5 μg/l, decreased on the second day – 429±198.9 μg/l (p&lt;0.05), approaching the indicators of the EPB and early PB groups (487±267.0 and 397±202.3 μg/l; p&gt;0.05) and pregnant women of the same term.Hb decreased to 106±8.9 g/l, and Ht – to 35±6.1% with the progression of pregnancy. In parturients of the PB group, they were probably higher than the indicators of pregnant women of the corresponding terms, increasing on the second day after delivery – 110±6.7 g/l and 41±3.1%.There was no significant blood loss in the clinical groups. In all pregnant and parturient women the APTT and PI indicators varied from 27.0±3.51 s to 35.4±3.43 s and from 88±4.8% to 101±5.2%, respectively.Conclusions. 1. A gradual increase in the fibrinogen (FG) concentration with increasing gestational age from 4.2±0.56 g/l in 22–27 weeks to 4.4±0.57 g/l by the time of delivery indicates an increase in the level of FG in healthy pregnant women as an adaptive response of the body to the formation of an additional vascular system.2. An excessive FG increase is a consequence of hemoconcentration, not absolute hyperfibrinogenemia, and may be a sign of pathological processes underlying hypovolemia. In case of extremely preterm birth (EPB), the concentration of FG in the parturient was 4.5±0.81 g/l. Higher values of FG, hemoglobin, and hematocrit in parturients with EPB than in pregnant women at the same term are evidence of insufficient hemodilution, which can be considered as one of the pathogenetic mechanisms of premature labor.3. Laboratory indicators of the blood coagulation system – APTT, PI – in the absence of bleeding have no diagnostic value.

Internalization of nano- and micro-plastics in human erythrocytes leads to oxidative stress and estrogen receptor-mediated cellular responses

Plastic material versatility has resulted in a substantial increase in its use in several sectors of our everyday lives. Consequently, concern regarding human exposure to nano-plastics (NPs) and micro-plastics (MPs) has recently increased. It has been shown that plastic particles entering the bloodstream may adhere to the erythrocyte surface and exert adverse effects following erythrocyte aggregation and adhesion to blood vessels. Here, we explored the effects of polystyrene nano-plastics (PS-NPs) and micro-plastics (PS-MPs) on human erythrocytes. Cellular morphology, binding/internalization of PS-NPs and PS-MPs, oxidative stress parameters, as well as the distribution and anion exchange capability of band 3 (anion exchanger 1; SLC4A1) have been analyzed in human erythrocytes exposed to 1 μg/mL PS-NPs or PS-MPs for 3 and 24 h, respectively. The data obtained showed significant modifications of the cellular shape after exposure to PS-NPs or PS-MPs. In particular, a significantly increased number of acanthocytes, echinocytes and leptocytes were detected. However, the percentage of eryptotic cells (<1 %) was comparable to physiological conditions. Analytical cytology and confocal microscopy showed that PS-NPs and PS-MPs bound to the erythrocyte plasma membrane, co-localized with estrogen receptors (Erα/ERβ), and were internalized. An increased trafficking from the cytosol to the erythrocyte plasma membrane and abnormal distribution of ERs were also observed, consistent with ERα-mediated binding and internalization of PS-NPs. An increased phosphorylation of ERK1/2 and AKT kinases indicated that an activation of the ER-modulated non-genomic pathway occurred following exposure to PS-NPs and PS-MPs. Interestingly, PS-NPs or PS-MPs caused a significant production of reactive oxygen species, resulting in an increased lipid peroxidation and protein sulfhydryl group oxidation. Oxidative stress was also associated with an altered band 3 ion transport activity and increased oxidized haemoglobin, which led to abnormal clustering of band 3 on the plasma membrane. Taken together, these findings identify cellular events following the internalization of PS-NPs or PS-MPs in human erythrocytes and contribute to elucidating potential oxidative stress-related harmful effects, which may affect erythrocyte and systemic homeostasis.

Study of some components of the influence and formation of blood flow in patients with "slow flow".

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

On the Origin of the Photoplethysmography Signal: Modeling of Volumetric and Aggregation Effects

This study aimed to examine the mechanisms of the photoplethysmography (PPG) signal formation using Monte Carlo simulations of light transport in biological tissues and experimental observations. Based on a three-layer skin model in backscattering geometry, we sequentially simulated volumetric blood changes and the aggregation/disaggregation of erythrocytes in the dermal layer and estimated their contribution to the registered PPG signal. The calculations were conducted for two wavelengths: 525 nm and 810 nm. For green light, absorption predominates over scattering in the formation of a PPG signal, whereas, for near-infrared light, scattering prevails over absorption. This theoretical result was verified using the Modified Beer–Lambert law and clinical in vivo PPG data of seven healthy subjects. Changes in the size of the scatterers during erythrocyte aggregation and disaggregation can significantly contribute to the PPG signal at near-infrared light. Thus, for the green waveband, the classical volumetric model can be considered dominant in the PPG signal formation. In contrast, for the near-infrared range, both volumetric and aggregation effects must be considered as being approximately equal.

Integrating UPLC-Q-TOF-MS and Network Pharmacology to Explore the Potential Mechanisms of Paeonia lactiflora Pall. in the Treatment of Blood Stasis Syndrome.

Paeonia lactiflora Pall. (PLP) is thought to promote blood circulation and remove blood stasis. This study used blood component analysis, network pharmacology, and molecular docking to predict the mechanism of PLP in the treatment of blood stasis syndrome (BSS). PLP was processed into Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). PRA and PRR could significantly reduce whole blood viscosity (WBV) at 1/s shear rates and could increase the erythrocyte aggregation index (EAI), plasma viscosity (PV), and erythrocyte sedimentation rate (ESR) of rats with acute blood stasis. They prolonged the prothrombin time (PT), and PRR prolonged the activated partial thromboplastin time (APTT). PRA and PRR increased the thrombin time (TT) and decreased the fibrinogen (FBG) content. All the results were significant (p < 0.05). Ten components of Paeoniflorin, Albiflorin, Paeonin C, and others were identified in the plasma of rats using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A protein-protein interaction network (PPI) analysis showed that AKT1, EGFR, SRC, MAPK14, NOS3, and KDR were key targets of PLP in the treatment of BSS, and the molecular docking results further verified this. This study indicated that PLP improves BSS in multiple ways and that the potential pharmacological mechanisms may be related to angiogenesis, vasoconstriction and relaxation, coagulation, and the migration and proliferation of vascular cells.

Intermittent hypoxia training does not change erythrocyte aggregation indicators in young, healthy men.

The increasing popularity of hypoxic training as a training method to improve physical performance indicates the need to study the effects of this type of intervention on blood morphological and rheological indices, since the adaptive changes that follow such training mainly affect blood indices. In this study, the effects of a 4weeks of intermittent hypoxic training on blood morphological and rheological indicators in physically active men were assessed. Forty-eight young, physically active men, participated in the study. Participants were randomly divided into three groups: two training groups and a control group without intervention (CTRL). Each group consisted of 16 participants. Training groups performed interval training (three times per week, 4weeks, 12 workouts) under different conditions: in hypoxia (IHT; fraction of inspired oxygen (FiO2) = 14.4%) or in normoxia (NT; FiO2 = 20.9%). The control group performed only two workouts 4weeks apart. Blood was taken during the first and last training session at rest, and 3minutes after training. After the last training session, there was a significant increase in mean corpuscular volume and a decrease in mean corpuscular haemoglobin concentration measured at rest only in the IHT group. There was also a significant decrease in resting aggregation amplitude for the IHT and CTRL groups. There was no difference in change of post-exercise plasma volume between first and last training session. The applied intermittent interval training in conditions of normoxia and hypoxia had no significant impact on resting aggregation parameters. This suggest that training under hypoxic conditions does not cause adverse rheological changes.

Effect of alprostadil plus cilostazol on the treatment outcomes and inflammatory factors in patients with lower extremity arteriosclerosis obliterans receiving evidence-based care.

This study aims to elucidate the effect of alprostadil (ALP) plus cilostazol (CIL) on the treatment outcomes and inflammatory factors in patients with lower extremity arteriosclerosis obliterans (LEASO) receiving evidence-based care. Firstly, 130 patients with LEASO were selected from February 2020 to February 2023 and then randomly divided into two groups with 65 patients each. Excluding the dropouts, 59 patients in the control group (6 cases of dropout) received ALP and 62 patients in the research group (3 cases of dropout) received ALP plus CIL. Both groups were cared for in accordance with the evidence-based care model. Treatment outcomes, arteriosclerosis indexes (blood flow of dorsalis pedis artery [DPA], ankle-brachial index [ABI] and toe-brachial index [TBI]), hemorheological parameters (erythrocyte aggregation index [EAI], erythrocyte deformation index [EDI], high blood viscosity [HBV] and haematocrit [HCT]), inflammatory factors (interleukin [IL]-6, IL-8 and tumour necrosis factor [TNF]-α) and complications (nausea, diarrhoea, headache and transaminase elevation) were compared between the control and research groups. Results show that the overall response rate was markedly higher in the research group (90.32%) than in the control group (74.58%). Additionally, the blood flow of DPA, ABI and TBI in the research group significantly increased after the treatment and were higher than those in the control group. Meanwhile, the EAI, EDI, HBV, HCT, IL-6, IL-8 and TNF-α were significantly lower. The two groups did not differ markedly in the complication rate. The above findings suggest that ALP plus CIL is effective for patients with LEASO receiving evidence-based care. It can significantly improve arteriosclerosis indexes and hemorheological parameters while inhibiting serum inflammatory responses, with some certain safety.

Erythrocyte aggregability, and fibrinogen during atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Academician N. Kipshidze University Clinic - Republican Hospital; IVANE BERITASHVILI CENTER OF EXPERIMENTAL BIOMEDICINE, Department of rheology and diagnostic analytical services. Introduction Despite all biomedical efforts, the prevalence of atrial fibrillation and its associated morbidity and mortality are increasing globally year after year. The disease's unfavorable epidemiological picture determined the reality of the project. There are many hypotheses to explain the pathogenesis of atrial fibrillation. All the hypotheses are based on mechanisms at local points and microwaves (in whole or in part). None of them consider the role of hemodynamics and hemorheology in the formation and progression of atrial fibrillation. It is also unknown how atrial fibrillation affects intracardiac macro- and microcirculation. Purpose The goals of this project were to determine how hemodynamics and hemorheology change in patients with atrial fibrillation. In order to gain a better understanding of the pathological processes underlying AF, we sought to access the relationships between hemodynamics, rheological properties,and the coagulation system of blood. Methods The Erythrocyte (RBC) Aggregation Index (EAI) was monitored in the development and validation cohorts (90 patients and 20 healthy individuals) using the textural analysis system (Tas-Plus, Leitz, Germany) and an innovative "Georgian technique" with the unique function of a quantitative assessment of the EAI. The method was developed by Georgian scientists and is well-known around the world for being direct, numerical, and precise. In all patients Coagulogram and 12-lead standard ECG were performed. Results According to the data obtained, the patients' rheological and coagulation system conditions are the same, and they are distinct from the control group. During the statistical processing of the total amount of fibrinogen (Fib), the patients were divided into three categories. The average Fib in Category I patients was 336.40 ±27,77 mg/dl, and the average EAI-RBC value was 32.8± 9.4. Category II: FIB: 373.00±22.65mg/dl; EAI-RBC: 39.8±13.8 and Category III: FIB:471.27±21.58 mg/dl; EAI-RBC: 42.6±10.4. The control group: FIB: 301±18,1 mg/dl, EAI-RBC: 25.6±1.29. Fibrinogen and the Index of Erythrocyte Aggregation were found to have a linear relationship. The higher the concentration of fibrinogen, the more severe the hemorheological disorders. It should be noted that the categories were chosen without taking into account the forms of atrial fibrillation. Conclusions The findings clearly show the existence of two parallel mechanisms in the body. These are the coagulation systems, characterized by dynamic equilibrium, and the rheology systems, which lack a physiologically balanced opposing system. Coagulation control does not accurately describe hemorheological parameters, which are one of the most powerful mechanisms for atrial fibrillation formation In order to better understand the diseases' occurrence and progression, the simultaneous studies of fibrinogen concentration and rheological parameters are especially important for both fundamental and practical medicine.

Ameliorative delivery of docetaxel and curcumin using PEG decorated lipomers: A cutting-edge in-vitro/ in-vivo appraisal

The development of a PEG-decorated lipid-polymer hybrid system camouflaged with natural and synthetic chemotherapeutic moieties is an influential approach melding the biomimetic properties of long-circulating vesicles to utilize different mechanisms to dwindle the tumor growth. Therefore, a safe and efficient lipid-coated nano-particulate system (LCNPs) was proposed to investigate the in-vitro, ex-vivo and in-vivo demeanors of such amalgamation.Docetaxel loaded PLGA nanoparticles (DTX-NPs) were prepared by solvent evaporation while curcumin liposomes were mapped out using the film hydration method. Physicochemical characterizations were executed in terms of size, surface morphology, differential scanning calorimetry (DSC) and fourier-transform infrared spectroscopy (FTIR). In-vitro cytotoxicity was effectuated using MCF-7 cell line. Hemolysis, erythrocyte aggregation and acute in-vivo toxicity were carried out to establish the biocompatibility. The hydrodynamic diameters of samples were in the nano-range and corresponded to the findings of scanning electron microscopy (SEM) and atomic force microscopy (AFM). The absence of distinctive peaks of DTX-NPs in FTIR and DSC analysis of LCNPs depicts the shielding of the lipid bilayer over the nanoparticle. Cytotoxicity induced by the LCNPs represented the efficient delivery of cargo to the tumor cells. LCNPs also exhibited the least toxicity under ex-vivo and in-vivo circumstances compared to free drugs. Additionally, histological studies showed no evidence of substantial necrosis. Additionally, histological studies showed no evidence of notable necrosis.