Plasma Components Research Articles

Pharmacokinetics integrated with network pharmacology to clarify effective components and mechanism of Wendan decoction for the intervention of coronary heart disease

Ethnopharmacological relevanceCoronary heart disease (CHD), one of the leading causes of mortality in the world among chronic non-infectious diseases, is closely associated with atherosclerosis, which ultimately leads to myocardial injury. Wendan decoction (WDD), a classical famous formula, exerted an intervention effect on CHD according to numerous reports. However, the effective components and underlying mechanisms for the treatment of CHD have not been fully elucidated. Aim of the studyAn in-depth investigation of the effective components and mechanisms of WDD for the intervention of CHD was further explored. Materials and methodsFirstly, based on our previous metabolic profile results, a quantification method for absorbed components was established by ultra-performance liquid chromatography triple quadrupole-mass spectrometry (UPLC-TQ-MS) and applied to the pharmacokinetics study of WDD. Then the network pharmacology analysis for considerable exposure components in rat plasma was employed to screen key components of WDD. Gene ontology and KEGG pathway enrichment analysis were further performed to obtain putative action pathways. The effective components and mechanism of WDD were confirmed by in vitro experiments. ResultsA rapid and sensitive quantification method was successfully applied to the pharmacokinetic study of 16 high-exposure components of WDD at three different doses. A total of 235 putative CHD targets were obtained for these 16 components. Then, 44 core targets and 10 key components with high degree values were successively screened out by the investigation of protein-protein interaction and the network of “herbal medicine-key components-core targets”. Enrichment analysis suggested that the PI3K-Akt signaling pathway was closely related to this formula's therapeutic mechanism. Furthermore, pharmacological experiments demonstrated that 5 of 10 key components (liquiritigenin, narigenin, hesperetin, 3,5,6,7,8,3′,4′-heptamethoxyflavone, and isoliquiritigenin) significantly enhanced DOX-induced H9c2 cell viability. The cardioprotective effects of WDD against DOX-induced cell death through the PI3K-Akt signaling pathway were verified by western blot experiments. ConclusionThe integration of pharmacokinetics and network pharmacology approaches successfully clarified 5 effective components and therapeutic mechanism of WDD for the intervention of CHD.

Quorum sensing-associated bacterial phenazines are potential ligands of human α1 -acid glycoprotein.

α1 -Acid glycoprotein (AGP) is a prominent acute phase component of blood plasma and extravascular fluids. As a member of the immunocalins, AGP exerts protective effects against Gram-negative bacterial infections but the underlying molecular mechanisms still need to be elucidated. Notably, the chemical structures of phenothiazine, phenoxazine and acridine type ligands of AGP are similar to those of phenazine compounds excreted by the opportunistic human pathogen Pseudomonas aeruginosa and related bacterial species. These molecules, like pyocyanin, act as quorum sensing-associated virulence factors and are important contributors to bacterial biofilm formation and host colonisation. Molecular docking simulations revealed that these agents fit into the multi-lobed cavity of AGP. The binding site is decorated by several aromatic residues which seem to be essential for molecular recognition of the ligands allowing multifold π-π and CH-π interactions. The estimated affinity constants (~105 M-1 ) predict that these secondary metabolites could be trapped inside the β-barrel of AGP which in turn could reduce their cytotoxic effects and disrupt the microbial QS network, facilitating the eradication of bacterial infections.

Effects of Rheum rhaponticum and Rheum rhabarbarum extracts on haemostatic activity of blood plasma components and endothelial cells in vitro

Ethnopharmacological relevanceTraditional medicine recommends the use of Rheum rhaponticum L. and R. rhabarbarum L. to treat over thirty complaints, including disorders related to the cardiovascular system such as heartache, pains in the pericardium, epistaxis and other types of haemorrhage, blood purification as well as disorders of venous circulation. Aim of the studyThis work was dedicated to examining for the first time the effects of extracts from petioles and roots of R. rhaponticum and R. rhabarbarum, as well as two stilbene compounds (rhapontigenin and rhaponticin) on the haemostatic activity of endothelial cells and functionality of blood plasma components of the haemostatic system. Materials and methodsThe study was based on three main experimental modules, including the activity of proteins of the human blood plasma coagulation cascade and the fibrinolytic system as well as analyses of the haemostatic activity of human vascular endothelial cells. Additionally, interactions of the main components of the rhubarb extracts with crucial serine proteases of the coagulation cascade and fibrinolysis (i.e. thrombin, the coagulation factor Xa and plasmin) were analyzed in silico. ResultsThe examined extracts displayed anticoagulant properties and significantly reduced the tissue factor-induced clotting of human blood plasma (by about 40%). Inhibitory effects of the tested extracts on thrombin and the coagulation factor Xa (FXa) were found as well. For the extracts, the IC50 was ranging from 20.26 to 48.11 μg/ml. Modulatory effects on the haemostatic response of endothelial cells, including the release of von Willebrand factor, tissue-type plasminogen activator and the plasminogen activator inhibitor-1, have been also found. ConclusionsOur results indicated for the first time that the examined Rheum extracts influenced the haemostatic properties of blood plasma proteins and endothelial cells, with the prevalence of the anticoagulant action. The anticoagulant effect of the investigated extracts may be partly attributed to the inhibition of the FXa and thrombin activities, the key serine proteases of the blood coagulation cascade.

Pathophysiological Role of Microglial Activation Induced by Blood-Borne Proteins in Alzheimer's Disease.

The blood-brain barrier (BBB) restricts entry of neurotoxic plasma components, blood cells, and pathogens into the brain, leading to proper neuronal functioning. BBB impairment leads to blood-borne protein infiltration such as prothrombin, thrombin, prothrombin kringle-2, fibrinogen, fibrin, and other harmful substances. Thus, microglial activation and release of pro-inflammatory mediators commence, resulting in neuronal damage and leading to impaired cognition via neuroinflammatory responses, which are important features observed in the brain of Alzheimer's disease (AD) patients. Moreover, these blood-borne proteins cluster with the amyloid beta plaque in the brain, exacerbating microglial activation, neuroinflammation, tau phosphorylation, and oxidative stress. These mechanisms work in concert and reinforce each other, contributing to the typical pathological changes in AD in the brain. Therefore, the identification of blood-borne proteins and the mechanisms involved in microglial activation and neuroinflammatory damage can be a promising therapeutic strategy for AD prevention. In this article, we review the current knowledge regarding the mechanisms of microglial activation-mediated neuroinflammation caused by the influx of blood-borne proteins into the brain via BBB disruption. Subsequently, the mechanisms of drugs that inhibit blood-borne proteins, as a potential therapeutic approach for AD, along with the limitations and potential challenges of these approaches, are also summarized.

Porcine spermadhesin AQN-3 binds to negatively charged phospholipids

The spermadhesin AQN-3 is a major component of porcine seminal plasma. While various studies suggest that this protein binds to boar sperm cells, its attachment to the cells is poorly understood. Therefore, the capacity of AQN-3 to interact with lipids was investigated. For that purpose, AQN-3 was recombinantly expressed in E. coli and purified via the included His-tag. Characterizing the quaternary structure by size exclusion chromatography revealed that recombinant AQN-3 (recAQN-3) is largely present as multimer and/or aggregate. To determine the lipid specificity of recAQN-3, a lipid stripe method and a multilamellar vesicle (MLV)-based binding assay were used. Both assays show that recAQN-3 selectively interacts with negatively charged lipids, like phosphatidic acid, phosphatidylinositol phosphates, and cardiolipin. No interaction was observed with phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, or cholesterol. The affinity to negatively charged lipids can be explained by electrostatic interactions because binding is partly reversed under high-salt condition. However, more factors have to be assumed like hydrogen bonds and/or hydrophobic forces because the majority of bound molecules was not released by high salt. To confirm the observed binding behavior for the native protein, porcine seminal plasma was incubated with MLVs comprising phosphatidic acid or phosphatidyl-4,5-bisphosphate. Attached proteins were isolated, digested, and analyzed by mass spectrometry. Native AQN-3 was detected in all samples analyzed and was – besides AWN – the most abundant protein. It remains to be investigated whether AQN-3, together with other sperm associated seminal plasma proteins, acts as decapacitation factor by targeting negative lipids with signaling or other functional roles in fertilization.

Pharmacokinetic-pharmacodynamic (PK/PD) modeling to study the hepatoprotective effect of Perilla Folium on the acute hepatic injury rats

Ethnopharmacological relevancePerilla Folium (PF), is a traditional medicinal material with the homology of medicine and food in China and has been widely used due to its rich nutritional content and medicinal value. The hepatoprotective effects of PF extract include their protection against acute hepatic injury, tert-butylhydroperoxide (t-BHP) induced oxidative damage, and Lipopolysaccharide (LPS) and D-galactosamine (D-GalN) induced hepatic injury have been well studied. However, there are few reports on the pharmacokinetics studies of PF extract in acute hepatic injury model rats, and the anti-hepatic injury activity of PF is still unclear. Aim of the studyThe differences in the plasma pharmacokinetic of 21 active compounds between the normal and model groups were compared， and established pharmacokinetics/pharmacodynamics (PK/PD) modeling was to analyze the hepatoprotective effects of PF. Materials and methodsThe acute hepatic injury model was induced with an intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-GalN), and the plasma pharmacokinetics of 21 active compounds of PF were analyzed in the normal and model groups using ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). The correlation between plasma components and hepatoprotective effects indicators (the alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase (LDH)) in the model group was also investigated and established a Pharmacokinetic/pharmacodynamic (PK/PD) correlation analysis of the hepatoprotective effects of PF. ResultsThe results revealed that organic acid compounds possessed the characteristics of faster absorption, shorter peak time and slower metabolism, while the flavonoid compounds had slower absorption and longer peak time, and the pharmacokinetics of various components were significantly affected after modeling. The results of PK/PD modeling analysis demonstrated that the plasma drug concentration of each component existed a good correlation with the three AST, ALT, and LDH, and the lag time of the efficacy of each component is relatively long. ConclusionsThe plasma drug concentration of each component existed a good correlation with the three AST, ALT, and LDH, and the lag time of the efficacy of each component is relatively long in vivo.

Determination of multicomponents from Zhuanggu Guanjie capsule in ratplasma by UHPLC-MS/MS and pharmacokinetic study.

Aim: To develop a UHPLC-MS/MS method for the quantification of 12 constituents in rat plasma after oral administration of Zhuanggu Guanjie. Methods: Constituent separation was performed on a C18 column, and the mass spectrometric detection was performed in multiple reaction monitoring mode with a positive-negative ionization mode. Results: The method was successfully applied to the pharmacokinetic study of these 12 constituents after rats taking Zhuanggu Guanjie capsules. The results showed that psoralen, isopsoralen and aspersaponin VI were the key effective components and had high exposure. Conclusion: A rapid, simple and sensitive ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry method for the detection of 12 components in rat plasma after taking Zhuanggu Guanjie was developed and applied in this pharmacokinetics study.

Forecasting Heliospheric CME Solar-Wind Parameters Using the UCSD Time-Dependent Tomography and ISEE Interplanetary Scintillation Data: The 10 March 2022 CME

Remotely sensed interplanetary scintillation (IPS) data from the Institute for Space-Earth Environmental Research (ISEE), Japan, allows a determination of solar-wind parameters throughout the inner heliosphere. We show the 3D analysis technique developed for these data sets that forecast plasma velocity, density, and component magnetic fields at Earth, as well at the other inner heliospheric planets and spacecraft. One excellent coronal mass ejection (CME) example that occurred on the 10 March 2022 was viewed not only in the ISEE IPS analyses, but also by the spacecraft near Earth that measured the CME arrival at one AU. Solar Orbiter, that was nearly aligned along the Earth radial at 0.45 AU, also measured the CME in plasma density, velocity, and magnetic field. BepiColombo at 0.42 AU was also aligned with the STEREO A spacecraft, and viewed this CME. The instruments used here from BepiColombo include: 1) the European-Space-Agency Mercury-Planetary-Orbiter magnetic field measurements; 2) the Japan Aerospace Exploration Agency Mio spacecraft Solar Particle Monitor that viewed the CME Forbush decrease, and the Mercury Plasma Experiment/Mercury Electron Analyzer instruments that measured particles and solar-wind density from below the spacecraft protective sunshield covering. This article summarizes the analysis using ISEE, Japan real-time data for these forecasts: it provides a synopsis of the results and confirmation of the CME event morphology after its arrival, and discusses how future IPS analyses can augment these results.

Cover Picture: Astron. Nachr. 04/2023

Visualization of the results of a loop of spectral fits onto the time-averaged XMM-Newton / RGS spectrum of the Ultraluminous X-ray source NGC 247 ULX-1. The parameter space explored by the spectral fits covers a range of wind velocities (as constrained by the Doppler shift of the absorption lines) and photoionization parameters 𝜉 (an indicator of the wind temperature measured through the relative line ratios). The color code of the 2D map indicates, for each individual spectral fit, the improvement provided by the wind plasma component on the broadband continuum model. The black contours show the (2.0, 2.5, … 5.0 sigma) confidence levels, suggesting that the wind blows at about 17% of the speed of light. These results provide one of the most convincing detections of a hot plasma outflow in ultraluminous X-ray sources, the very first in the subclass of the supersoft sources. The implications of this discovery are discussed in the contribution of C. Pinto and P. Kosec, this issue, e20220134

Analysis of technological possibilities of N‒O‒C‒H system arc plasma in surface engineering processes

The object of this study was the substances that could be used to generate arc plasma. Conventional and promising plasma media were analyzed in order to identify the most universal one in terms of a set of properties for efficient energy transfer of material. It is shown that the mean-enthalpy media have a harmonious ratio of temperature and enthalpy and could provide a change in the energy state of the processed material with maximum efficiency. It is established that the most universal set of properties is demonstrated by the medium enthalpy plasma of the N‒O‒C‒H system. The use of mixtures of air with hydrocarbons for its generation makes it possible to reach the average mass temperature of (5...7)·103 K and change the oxidative-reducing potential of the plasma medium over a wide range. Given this, heat treatment is possible with maximum preservation of the original composition of the material. Experimental studies of plasma flows of the N‒O‒C‒H system confirmed the presence of reducing components capable of binding oxygen to air that is sucked into the jet. On rich mixtures, the oxygen content in the jet at a distance of 100 mm does not exceed 5 %. The positive effect of combined energy input into plasma-forming substance on the process of generation and formation of plasma jet has been proven. The use of energy of different physical nature makes it possible to maintain the local energy parameters of the plasma flow during material processing. This is due to the release of additional heat as a result of the interaction of plasma and plasma components with ambient air. The use of plasma of the N‒O‒C‒H system in surface engineering technologies could expand the range of processed materials and reduce the operating costs of the process

Toxic effects of microplastic (polyethylene) exposure: Bioaccumulation, hematological parameters and antioxidant responses in crucian carp, Carassius carassius

The purpose of this study was to evaluate the toxic effects of polyethylene microplastics (PE-MPs) by measuring the bioaccumulation, hematological parameters, and antioxidant responses in crucian carp (Carassius Carassius) exposed to waterborne 22–71 μm PE-MPs. C. carassius (mean weight, 24.0 ± 2.1 g; mean length, 13.1 ± 1.2 cm) were exposed to PE-MPs at concentration of 0, 4, 8, 16, 32, and 64 mg/L for 2 weeks. The accumulation of PE-MPs in each tissue of C. carassius was significantly increased in proportion to the PE-MPs concentration; the highest accumulation was observed in the intestine, followed by the gills and liver. Hematological parameters, plasma components and antioxidants responses were significantly affected by PE-MPs in a concentration-dependent manner. Exposure to ≥32 mg/L PE-MPs induced a significant decrease in red blood cells (RBCs), hemoglobin (Hb) content, and hematocrit values. However, exposure to ≥32 mg/L PE-MPs induced oxidative stress in the liver, gill, and intestine of C. carassius, thereby resulting in a significant increase in the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) and a decrease in glutathione (GSH) levels. The effects of interaction between the PE-MPs and exposure periods showed no significant changes in bioaccumulation, hematological parameters, plasma components and antioxidant responses. These finding indicate that the exposure to ≥32 mg/L PE-MPs could cause a significant accumulation in specific tissues of C. carassius, resulting in changes in hematological parameters, plasma components, and antioxidant responses. However, the interaction between PE-MPs and exposure periods had no significant effects, thereby suggesting the lack of toxicological interactions between PE-MPs and exposure periods in C. carassius.

Investigation of paint removal by atmospheric pressure plasma jet

Acrylic polyurethane paint on the surface of 2A12 Al alloy was cleaned utilizing an atmospheric pressure plasma jet in this work. The dynamic evolution of the paint removal process during plasma treatment with time was explored through analysis of morphology and chemical states. The results showed that although the thickness of paint could be reduced effectively with an increase in cleaning time, the removal rate of paint gradually decreased with time. During the initial cleaning process range, its original smooth morphology of paint turned rugged quickly and was almost unchanged with further plasma treatment. Element and chemical state analysis showed that the content of C in the paint layer decreased obviously after plasma treatment. In contrast, the O content increased remarkably. The cleaning mechanism could be mainly attributed to the reaction between active O-containing species in air plasma and organic components in the paint. After removal of superficial organic matter, residue inorganic metal oxide substances aggregated on the base. The exposed metal oxides on the one hand elevated the superficial O content, but on the other hand hindered further plasma penetration, resulting in a gradual decrease in cleaning rate with cleaning time. Therefore, physical wiping was proposed to be incorporated with the plasma method and effective removal of paint was realized.

Particle Size-Dependent Component Separation Using Serially Arrayed Micro-Chambers.

The purpose of this research was to enable component separation based on simple control of the flow rate. We investigated a method that eliminated the need for a centrifuge and enabled easy component separation on the spot without using a battery. Specifically, we adopted an approach that uses microfluidic devices, which are inexpensive and highly portable, and devised the channel within the fluidic device. The proposed design was a simple series of connection chambers of the same shape, connected via interconnecting channels. In this study, polystyrene particles with different sizes were used, and their behavior was evaluated by experimentally observing the flow in the chamber using a high-speed camera. It was found that the objects with larger particle diameters required more time to pass, whereas the objects with smaller particle diameters flowed in a short time; this implied that the particles with a smaller size could be extracted more rapidly from the outlet. By plotting the trajectories of the particles for each unit of time, the passing speed of the objects with large particle diameters was confirmed to be particularly low. It was also possible to trap the particles within the chamber if the flow rate was below a specific threshold. By applying this property to blood, for instance, we expected plasma components and red blood cells to be extracted first.

Simultaneous determination of multiple components in rat plasma by UHPLC-sMRM for pharmacokinetic studies after oral administration of Qingjin Yiqi Granules.

As a Traditional Chinese Medicine prescription, Qingjin Yiqi Granules (QJYQ) provides an effective treatment for patients recovering from COVID-19. However, the pharmacokinetics characteristics of the main components of QJYQ in vivo are still unknown. An efficacious ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed and validated for the simultaneous determination of 33 components in rat plasma after oral administration of QJYQ. The plasma samples were precipitated with 400µL methanol/acetonitrile (1/1, v/v) and analyzed in scheduled multiple reaction monitoring mode. The linear relationship of the 33 components was good (r > 0.9928). The lower limit of quantification for 33 components ranged from 0.4-60.5ng/mL. The average recoveries and matrix effects of the analytes ranged from 72.9% to 115.0% with RSD of 1.4%-15.0%. All inter-day and intra-day RSDs were within 15.0%. After oral administration (3.15g/kg), the validated approach was effectively applied to the pharmacokinetics of main components of QJYQ. Finally, fifteen main constituents of QJYQ with large plasma exposure were obtained, including baicalin, wogonoside, wogonin, apigenin-7-O-glucuronide, verbenalin, isoferulic acid, hesperidin, liquiritin, harpagide, protocatechuic acid, p-Coumaric acid, ferulic acid, sinapic acid, liquiritin apioside and glycyrrhizic acid. The present research lays a foundation for clarifying the therapeutic material basis of QJYQ and provides a reference for further scientific research and clinical application of QJYQ.

Combined action of albumin and heparin regulates lipoprotein lipase oligomerization, stability, and ligand interactions.

Lipoprotein lipase (LPL), a crucial enzyme in the intravascular hydrolysis of triglyceride-rich lipoproteins, is a potential drug target for the treatment of hypertriglyceridemia. The activity and stability of LPL are influenced by a complex ligand network. Previous studies performed in dilute solutions suggest that LPL can appear in various oligomeric states. However, it was not known how the physiological environment, that is blood plasma, affects the action of LPL. In the current study, we demonstrate that albumin, the major protein component in blood plasma, has a significant impact on LPL stability, oligomerization, and ligand interactions. The effects induced by albumin could not solely be reproduced by the macromolecular crowding effect. Stabilization, isothermal titration calorimetry, and surface plasmon resonance studies revealed that albumin binds to LPL with affinity sufficient to form a complex in both the interstitial space and the capillaries. Negative stain transmission electron microscopy and raster image correlation spectroscopy showed that albumin, like heparin, induced reversible oligomerization of LPL. However, the albumin induced oligomers were structurally different from heparin-induced filament-like LPL oligomers. An intriguing observation was that no oligomers of either type were formed in the simultaneous presence of albumin and heparin. Our data also suggested that the oligomer formation protected LPL from the inactivation by its physiological regulator angiopoietin-like protein 4. The concentration of LPL and its environment could influence whether LPL follows irreversible inactivation and aggregation or reversible LPL oligomer formation, which might affect interactions with various ligands and drugs. In conclusion, the interplay between albumin and heparin could provide a mechanism for ensuring the dissociation of heparan sulfate-bound LPL oligomers into active LPL upon secretion into the interstitial space.

Blood component resuscitative strategies to mitigate endotheliopathy in a murine hemorrhagic shock model.

Resuscitation with plasma components has been shown to improve endotheliopathy induced by hemorrhagic shock, but the optimal resuscitation strategy to preserve the endothelial glycocalyx has yet to be defined. The aim of this study was to determine if resuscitation with lactated Ringer's (LR), whole blood (WB), packed red blood cells (RBCs), platelet-rich plasma (PRP), platelet poor plasma, balanced RBC:PRP (1:1), or day 14 (d14) RBC would best minimize endothelial damage following shock. Male C57BL/6 mice were hemorrhaged to a goal mean arterial pressure of 25 mm Hg for 1 hour. Unshocked sham mice served as controls. Mice were then resuscitated with equal volumes of LR, WB, RBC, PRP, platelet poor plasma, 1:1, or d14 RBC and then sacrificed at 1, 4, or 24 hours (n = 5). Serum was analyzed for syndecan-1, ubiquitin C-terminal hydrolase L1, and cytokine concentrations. Lungs underwent syndecan-1 immunostaining, and lung injury scores were calculated after hematoxylin and eosin. Proteolytic cleavage of the endothelial glycocalyx was assessed by serum matrix metalloprotease 9 levels. Serum syndecan-1 and ubiquitin C-terminal hydrolase L1 levels were significantly increased following resuscitation with d14 RBC compared with other groups. Early elevation in lung syndecan-1 staining was noted in LR-treated mice, while d14 mice showed decreased staining compared with sham mice following shock. Lung injury scores were significantly elevated 4 hours after resuscitation with LR and d14 RBC compared with WB. Serum matrix metalloprotease 9 levels were significantly increased at 1 and 4 hours in d14 mice compared with sham mice. Systemic inflammation was increased in animals receiving LR, 1:1, or d14 RBC. Resuscitation with WB following hemorrhagic shock reduces endothelial syndecan-1 shedding and mitigates lung injury. Aged RBC and LR fail to attenuate endothelial injury following hemorrhagic shock. Further research will be necessary to determine the effect of each of these resuscitative fluids in a hemorrhagic shock model with the addition of tissue injury.

Abstract 5958: Analysis of MDSCs as a diagnostic and therapeutic target for gastric cancer

Abstract Background: Gastric cancer (GC) is the second most common cancer in Japan in terms of incidence and the third most common in terms of deaths. The onset and progression of cancer are generally suppressed by the action of immune cells, which is an inflammatory response. MDSCs are thought to promote cancer progression and invasion by suppressing the function of immune cells, making them potential therapeutic and diagnostic targets. We measured MDSCs in GC patients and observed more monocyte-derived MDSCs in peripheral blood in advanced GC than in early GC. However, granulocyte-derived MDSCs showed no difference in GC progression when markers for classical MDSCs were used. We considered that granulocyte-derived MDSCs were much more abundant than monocyte-derived MDSCs in peripheral blood and were involved in cancer progression. We hypothesized that we had a new granulocyte-derived marker for advanced GC that did not show differences in classical markers, but may have different functions, and aimed to identify a novel subset that may be a therapeutic and diagnostic target. Method: For GC patients, we used heparin blood samples provided by patients who consented to Juntendo University. We analyzed the expression of various cell surface proteins against populations of CD33high, CD66bhigh, and HLA-DRlow as classical markers of MDSCs derived from granulocytes of GC patients using FACS (Melody). MDSCs were isolated by a cell sorter and used for experiments such as RNA-Seq. Novel markers and involved cytokines were quantified in plasma components by cytometric bead array. Result: The chemokine receptors CCR2, CCR5, CXCR4, and CXCR5 were highly expressed in MDSCs of advanced GC patients. The ability to suppress T-cell activation was also found to be stronger in MDSCs with advanced GC. In addition, IL-10 produced by MDSCs was also more abundant in the plasma of patients with advanced GC, as well as chemokines according to chemokine receptors. Conclusion: The high expression of chemokine receptors on MDSCs in advanced GC may indicate that chemokines produced at the cancer site facilitate the migration of MDSCs. These novel subsets of MDSCs found in advanced GC suggest that they may be new therapeutic targets. Citation Format: Suguru Yamauchi, Takumi Iwasawa, Tomoaki Ito, Malcom V. Brock, Tetsu Fukunaga, Hajime Orita, Kazunori Kato. Analysis of MDSCs as a diagnostic and therapeutic target for gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5958.

Abstract SY30-02: Oncosomes in the early stages of breast cancer

Abstract Comprehensive analysis of cellular, acellular and plasma components of the Liquid Biopsy provides the opportunity to investigate cancer evolution and the interactions with the immune system at the systemic level in the individual patient. This presentation will discuss early findings supporting the relevance of oncosomes, large extracellular vesicles, in early-stage breast cancer and its potential utility in early detection and cell-level staging of the disease when combined with the cellular profiles. Breast cancer (BC) affects 1 in every 8 women in the United States and is currently the most prevalent cancer worldwide. Precise staging at diagnosis and prognosis are essential components for the clinical management of BC patients. We set out to evaluate the feasibility of a next generation liquid biopsy platform to stratify late-stage BC, early-stage BC, and age- and gender matched controls using peripheral blood samples. Utilizing 5 biomarkers, we can identify rare circulating events with epithelial, mesenchymal, endothelial and hematological origin. We detected a higher level of CTCs in late-stage patients, compared to the early-stage and normal donors. We observed more tumor-associated oncosomes in the early-stage, compared to late-stage and the normal donor groups. Overall, we were able to detect reproducible patterns in the enumeration of rare cells and oncosomes of cancer vs. normal donors with an AUC of 99%. An initial concept for cell-level staging with the liquid biopsy was applied to early-stage vs. late-stage BC samples and reached an AUC of 91% allowing for robust stratification. Citation Format: Peter Kuhn. Oncosomes in the early stages of breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY30-02.

Impact of Uncontrolled Diabetes Mellitus on Blood Cells Indices and Plasma Components in Patients Without Nephropathy.

<b>Background and Objective:</b> Diabetes mellitus (DM) the most prevalent consequences are diabetic retinopathy, neuropathy, cardiovascular illnesses, erectile dysfunctions, stroke and cardiovascular difficulties. The main goal of this study was to evaluate the impact of uncontrolled diabetes mellitus on blood cells' indices and plasma components. <b>Materials and Methods:</b> This is a prospective cross-sectional study. The research was carried out at the King Fahad Medical Center in Riyadh, in duration from February, 2023 to May, 2023, in the interest of healthcare consumers attending the hematology laboratory for routine investigations. Sixty samples were collected and complete blood count, lipid profile, HbA1c and blood glucose for blood samples. <b>Results:</b> In this study, females accounted for 53.3% of the participants, while males accounted for 46.7%. In terms of age distribution, more than 55 years old accounted for 50% of the study's participants. A significant correlation has been found between HbA1c and red blood cell Mean Cell Volume (MCV) and there was a significant association between the high level of HbA1c and the red blood count. However, there was no significant correlation between plasma components and HbA1c. <b>Conclusion:</b> There is a remarkable effect of uncontrolled diabetes mellitus and RBCs count and erythrocyte MCV.

Characteristics of atmospheric pressure Ar-plasma around a spherical particle: Numerical study

The characteristics of atmospheric pressure Ar-plasma such as the spatial distributions of number densities, fluxes, and temperatures of electrons and heavy plasma particles, as well as the spatial distribution of electric potential around an individual spherical particle, were studied numerically on the basis of the hydrodynamic (diffusion) equations for plasma components. The governing equations were formulated for plasma that is not in thermal and ionization equilibrium. The boundary conditions near the particle were set on the edge of the space charge layer (sheath) adjacent to the particle surface. The nonlinear problem was solved taking into account the temperature dependencies of transport and kinetic coefficients. The heat flux introduced by the plasma into the particle was calculated and compared with the results of the simple heat conduction model. The range 10 − 5 – 10 − 4 m of particle radius and the range 6–18 kK of unperturbed plasma temperature were considered.