Blood Plasma Proteins Research Articles

Hepatic Clearance Binding Terms of Hydrophobic Organic Chemicals in Rainbow Trout: Application of a Streamlined Sorbent-Phase Dosing Method

Knowledge of the freely dissolved chemical fraction in liver S9 incubation medium (ϕS9) and blood plasma (ϕP), often expressed as the ϕP/ϕS9 ratio or fU, plays a central role in in vitro–in vivo extrapolation of biotransformation rates for hydrophobic organic chemicals (HOCs) in fish. However, there are very few empirical fU data for adequately assessing the bioaccumulation potential of HOCs (i.e., log KOW ≥ 4) from in vitro biotransformation rates. In this study, we present a novel streamlined approach for obtaining the fU values of HOCs and produce some of the first empirical fU data for rainbow trout. We show that fU is relatively constant for substances with a log KOW of ≥4 and appears to be largely controlled by the relative differences in protein and lipid contents in blood plasma and liver S9 incubation media. Predictive fU models are in reasonable agreement with empirical observations. Empirical fU values for HOCs with a log KOW of ≥4 ranged between 0.015 and 0.096 with an average fU value of 0.044 at an S9 protein concentration of 1 mg/mL. This range of fU values may provide reasonable preliminary estimates for the extrapolation of biotransformation rates measured in trout liver S9 bioassays.

Troponins, Adhesion Molecules, and Interleukins as Diagnostic Markers of CVDs: Expression in Peripheral Tissues

Cardiovascular disease (CVD) is one of the main causes of mortality for middle-aged and elderly people in developed countries. The early diagnostic of CVD in middle-aged and elderly people is often hampered by the absence of characteristic clinical picture of the disease. The early diagnosis of atherosclerosis, coronary heart disease (CHD), and myocardial infarction (MI) and their correction improves the survival prognosis and the quality of life of patients. The concentration of the cardinal troponins hs-cTnT and hs‑cTnI, ICAM-1, the adhesion molecules V-CAM1, E-LAM1, and the IL-1α, 1β, -4, -5, -6, -13, -17 cytokines in blood plasma were studied in order to assess the effectiveness of the treatment of atherosclerosis, CHD, and MI. The study of the concentration of ICAM-1, growth factor GDF15, and the NOTCH1 transmembrane protein in blood plasma and urine was recommended for the predictive diagnostic of these diseases. Assessment of the expression of these signal molecules in peripheral tissues for the prediction and prognosis of CVD is a rapidly developing area of molecular medicine and gerontology.

Synthesis of bioactive glass-based coating by plasma electrolytic oxidation: Untangling a new deposition pathway toward titanium implant surfaces

HypothesisAlthough bioactive glass (BG) particle coatings were previously developed by different methods, poor particle adhesion to surfaces and reduced biological effects because of glass crystallization have limited their biomedical applications. To overcome this problem, we have untangled, for the first time, plasma electrolytic oxidation (PEO) as a new pathway for the synthesis of bioactive glass-based coating (PEO-BG) on titanium (Ti) materials. ExperimentsElectrolyte solution with bioactive elements (Na2SiO3-5H2O, C4H6O4Ca, NaNO3, and C3H7Na2O6P) was used as a precursor source to obtain a 45S5 bioglass-like composition on a Ti surface by PEO. Subsequently, the PEO-BG coating was investigated with respect to its surface, mechanical, tribological, electrochemical, microbiological, and biological properties, compared with those of machined and sandblasted/acid-etched control surfaces. FindingsPEO treatment produced a coating with complex surface topography, Ti crystalline phases, superhydrophilic status, chemical composition, and oxide layer similar to that of 45S5-BG (~45.0Si, 24.5 Ca, 24.5Na, 6.0P w/v%). PEO-BG enhanced Ti mechanical and tribological properties with higher corrosion resistance. Furthermore, PEO-BG had a positive influence in polymicrobial biofilms, by reducing pathogenic bacterial associated with biofilm-related infections. PEO-BG also showed higher adsorption of blood plasma proteins without cytotoxic effects on human cells, and thus may be considered a promising biocompatible approach for biomedical implants.

Identification of blood plasma proteins using heparin-coated magnetic chitosan particles

Heparin was immobilized on magnetic chitosan particles to be used as a tool for human plasma protein identification. Chitosan was magnetized by co-precipitation with Fe2+/Fe3+ (MAG-CH). Heparin was functionalized with carbodiimide and N-hydroxysuccinimide and covalently linked to MAG-CH (MAG-CH-hep). X-ray diffraction confirmed the presence of chitosan and Fe3O4 in MAG-CH. This particle exhibited superparamagnetism and size between 100–300 μm. Human plasma diluted with 10 mM phosphate buffer (pH 5.5) or 50 mM Tris-HCl buffer (pH 8.5) was incubated with MAG-CH-hep, and the proteins fixed were eluted with the same buffers containing increasing concentrations of NaCl. The proteins obtained were investigated by SDS-PAGE, LC/MS, and biological activity tests (PT, aPTT, and enzymatic chromogenic assay). Inhibitors of the serpin family, prothrombin, and human albumin were identified in this study. Therefore, MAG-CH-hep can be used to purify these proteins and presents the following advantages: low-cost synthesis, magnetic separation, ion-exchange purification, and reusability.

Estimation of Efficiency of Use of Dairy Products Enriched with Enter Sorbent Dietary Fibers on Immunophysiological Indicators of the Rat Organism

At all times, the problem of healthy and wholesome food has been one of the most important problems facing human society. This problem cannot be solved by simply increasing the amount of food consumed. Plant-based antioxidants are widely used for the prevention and treatment of diseases with the aim of eliminating free radicals from the body and restoring the body's antioxidant defense system. The article shows biochemical indicators that reflect the nature of changes in the early stages of the formation of response of the animal organism during toxic poisoning and the use of sour-milk products using enter sorbent dietary fiber from rice husk. With an increase in the dosage and frequency of CCl4 administration, the effect of deep poisoning and impaired lymph dynamics was obtained. Along with a decrease in the content of total protein and urea in lymph and blood plasma, an increase in ALT and AST levels in blood plasma by 2.5–3 times, as well as an increase in thymol test, were noted. Antioxidant defense mechanisms are universal in order to increase the body's vitality.

Tetrazine-TCO Ligation: A Potential Simple Approach to Improve Tumor Uptake through Enhanced Blood Circulation.

Targeted imaging via peptides has been extensively investigated for both diagnostic and therapeutic applications. However, peptides can be cleared out from the blood circulation quickly, leading to only moderate to low accumulation in regions of interest. Previously, 18F-sTCO-DiPhTz-RGDyK demonstrated relatively high blood retention with increased tumor uptake at the late time point (5.3 ± 0.4 and 8.9 ± 0.5%ID/g tumor uptake at 1 h p.i. and 4 h p.i., respectively). In this study, we aim to develop a novel platform based on TCO/tetrazine ligation that could be used not only to label the peptides with F-18 for PET but also to lead to increased or persistent tumor uptake potentially due to enhanced blood circulation of the labeled peptides. We first constructed systems containing different combinations of TCOs/tetrazines and found that the tetrazine moiety played a more important role to facilitate the enhanced blood circulation compared with TCO moiety. Four clinically relevant peptides including NT20.3, RGD, BBN, and exendin-4 were then evaluated, and the increased tumor uptake at a late time point was demonstrated by the combination of 18F-sTCO-DiPhTz system to NT20.3, RGD, and exendin-4. The plasma binding components of the PET agents were investigated by electrophoresis and autoradiography and indicated that transferrin and hemopexin could be the major proteins in blood plasma for binding with 18F-sTCO-DiPhTz conjugates. In summary, we have discovered a TCO/tetrazine system that could not only be used for PET probe construction but also potentially improve the tumor uptake and retention of fast-clearing peptides. Although additional binding experiments are still needed for some of the constructs, the promising preliminary result suggested that this strategy may be used to convert fast-clearing bioligands into relatively long circulating agents with enhanced tumor uptake/retention for either imaging or therapy applications.

The Effect of Choline Chloride Supplementation on the Reproductive Performance of Simmental Bulls Fed Protected Protein in the Ration

SOYXYL supplementation as a source of high-quality protected protein in rumen (Rumen Protected Protein) has proven to improve reproduction performance of bulls. The SOYXYL is an extrusion product of soybean (Glycine max) as a source of rumen protected protein. The potential of the protein supplementation is maximally expressed when it is supported by sufficient of metabolic rate. In this case the choline chloride supplementation increases the metabolic rate. The aim of the research was to analyze the effect of choline chloride supplementation on reproduction performance and hematologic status related to reproduction performance of bulls fed protected protein in the ration. The materials used were 12 bulls aged 5 years having weight of 700 ± 2.75 kg that were divided into 4 treatment groups, each of which consisted of 3 heads. The treatments applied were T0 (control): ration (grass + commercial concentrate) + protected protein supplement “SOYXYL”; T1: control + choline chloride 0.145% dry matter (DM) concentrate/head/day; T2: control + choline chloride 0.290% DM concentrate/head/day; T3: control + choline chloride 0.435% DM concentrate/head/day. Variables measured were nutrient consumption, blood lipid status, blood protein status, and reproduction performance. Data were analyzed using ANOVA in a completely randomized design and statistically processed using SAS program. The result showed that choline chloride supplementation by 0.435% from DM concentrate increased (p<0.05) the concentration of blood plasma protein, blood testosterone hormone, sperm concentration, and sperm motility from 6.44 g/dL, 4.66 ng/mL, 1006.74 million/mL, and 36.00%, respectively, in T0 to be 8.57 g/dL, 9.07 ng/ml, 1270.41 million/mL, and 70.00% in T3, respectively. The choline chloride supplementation up to 0.435% from DM concentrate to bulls supplemented with protected protein containing in the ration increased reproduction performance.

Evaluation of Aptamers as Affinity Reagents for an Enhancement of SRM-Based Detection of Low-Abundance Proteins in Blood Plasma.

Selected reaction monitoring (SRM) is a mass spectrometric technique characterized by the exceptionally high selectivity and sensitivity of protein detection. However, even with this technique, the quantitative detection of low- and ultralow-abundance proteins in blood plasma, which is of great importance for the search and verification of novel protein disease markers, is a challenging task due to the immense dynamic range of protein abundance levels. One approach used to overcome this problem is the immunoaffinity enrichment of target proteins for SRM analysis, employing monoclonal antibodies. Aptamers appear as a promising alternative to antibodies for affinity enrichment. Here, using recombinant protein SMAD4 as a model target added at known concentrations to human blood plasma and SRM as a detection method, we investigated a relationship between the initial amount of the target protein and its amount in the fraction enriched with SMAD4 by an anti-SMAD4 DNA-aptamer immobilized on magnetic beads. It was found that the aptamer-based enrichment provided a 30-fold increase in the sensitivity of SRM detection of SMAD4. These results indicate that the aptamer-based affinity enrichment of target proteins can be successfully employed to improve quantitative detection of low-abundance proteins by SRM in undepleted human blood plasma.

Modulating the Selectivity and Stealth Properties of Ellipsoidal Polymersomes through a Multivalent Peptide Ligand Display.

There is a need for improved nanomaterials to simultaneously target cancer cells and avoid non-specific clearance by phagocytes. An ellipsoidal polymersome system is developed with a unique tunable size and shape property. These particles are functionalized with in-house phage-display cell-targeting peptide to target a medulloblastoma cell line in vitro. Particle association with medulloblastoma cells is modulated by tuning the peptide ligand density on the particles. These polymersomes has low levels of association with primary human blood phagocytes. The stealth properties of the polymersomes are further improved by including the peptide targeting moiety, an effect that is likely driven by the peptide protecting the particles from binding blood plasma proteins. Overall, this ellipsoidal polymersome system provides a promising platform to explore tumor cell targeting in vivo.

Formulation and Evaluation of Protein Bound Paclitaxel Nanoparticles for Injectable Suspension

Aims: The aim of present study is to develop Paclitaxel nanoparticles for injectable suspension, an anti-neoplastic drug formulation.
 Study design: Mention the design of the study here.
 Place and Duration of Study: Sagar Institute of Research & Technology- Pharmacy, Ayodhya Bypass Road, Bhopal, between June 2017 and June2018.
 Methodology: The Human serum albumin (HSA) is the most abundant plasma protein in the human blood with a half-life of 19 days. It can reversibly bind hydrophobic drug substances, transport them in the body and release drugs at cell surface. The formulation is prepared by homogenization at high-pressure of paclitaxel in the presence of human serum albumin into a nanoparticle colloidal suspension. Paclitaxel nano particles have been stabilized by human albumin and maintain the average size of 100 nm
 Results: The particle size of the reconstituted solution is checked using the laser diffraction Technique the particle is White to yellow lyophilized after reconstitution the particle become homogeneous milky suspension without visible particulates. Reconstitution time NMT 25 minutes 20.45 sec. The assay was performed by HPLC and found to be 90.0% to 110.0% of label. The retention time of Paclitaxel peak obtained in sample corresponds to the respective standards obtained from standards the pH NLT 6.00 to NMT 8.00 Particle size NLT 100 nm – NMT 200 nm. Sterility test was comply as per USP <71>
 Conclusion: The nano-delivery systems could have the potential to be free of Cremophor EL and ethanol, enhance Paclitaxel solubility, improve Paclitaxel pharmacokinetic profiles in vivo, decrease its side effects, passively or actively target to tumor sites due to the EPR (Enhanced Permeability and Retention) effect and the use of targeting ligands, respectively, nanotechnology is a very active research area in both academic and industrial settings.
 Keywords: paclitaxel, Anti-cancer, nanotechnology, Injectable, Suspension

Early Detection of Alzheimer's Disease with Blood Plasma Proteins Using Support Vector Machines.

The successful development of amyloid-based biomarkers and tests for Alzheimer's disease (AD) represents an important milestone in AD diagnosis. However, two major limitations remain. Amyloid-based diagnostic biomarkers and tests provide limited information about the disease process and they are unable to identify individuals with the disease before significant amyloid-beta accumulation in the brain develops. The objective in this study is to develop a method to identify potential blood-based non-amyloid biomarkers for early AD detection. The use of blood is attractive because it is accessible and relatively inexpensive. Our method is mainly based on machine learning (ML) techniques (support vector machines in particular) because of their ability to create multivariable models by learning patterns from complex data. Using novel feature selection and evaluation modalities, we identified 5 novel panels of non-amyloid proteins with the potential to serve as biomarkers of early AD. In particular, we found that the combination of A2M, ApoE, BNP, Eot3, RAGE and SGOT may be a key biomarker profile of early disease. Disease detection models based on the identified panels achieved sensitivity (SN) > 80%, specificity (SP) > 70%, and area under receiver operating curve (AUC) of at least 0.80 at prodromal stage (with higher performance at later stages) of the disease. Existing ML models performed poorly in comparison at this stage of the disease, suggesting that the underlying protein panels may not be suitable for early disease detection. Our results demonstrate the feasibility of early detection of AD using non-amyloid based biomarkers.

Intermolecular recognition between pyrimethamine, an antimalarial drug and human serum albumin: Spectroscopic and docking study

In order to understand the transport of antimalarial drug, pyrimethamine (PYR) in human circulatory system, its recognition mechanism with the main carrier protein in blood plasma i.e., human serum albumin (HSA) was studied. PYR was found to quench the fluorescence spectrum of HSA in a progressive manner. The quenching constant showed inverse correlation with temperature, suggesting static quenching and formation of PYR-HSA complex. Ultraviolet absorption spectral results also supported complex formation between PYR and HSA. Value of Ka (2.04 × 104 M−1) at 298 K for PYR-HSA system characterized the binding affinity between PYR and HSA as moderate, while thermodynamic parameters (ΔS = +35.54 J mol−1 K−1 and ΔH = −10.60 kJ mol−1) disclosed the stabilizing forces being H-bonds, van der Waals and hydrophobic forces. Although PYR binding slightly modulated both secondary and tertiary structures of HSA along with changes in Tyr/Trp microenvironment, it increased protein's stability against thermal stress. Binding of PYR to HSA was predicted to be at Sudlow's Site I, as revealed from both site marker displacement and molecular docking results.

Polyelectrolyte Multilayer Films Modification with Ag and rGO Influences Platelets Activation and Aggregate Formation under In Vitro Blood Flow.

Surface functionalization of materials to improve their hemocompatibility is a challenging problem in the field of blood-contacting devices and implants. Polyelectrolyte multilayer films (PEMs), which can mimic functions and structure of an extracellular matrix (ECM), are a promising solution to the urgent need for functional blood-contacting coatings. The properties of PEMs can be easily tuned in order to provide a scaffold with desired physico-chemical parameters. In this study chitosan/chondroitin sulfate (Chi/CS) polyelectrolyte multilayers were deposited on medical polyurethane. Afterwards PEMs were modified by chemical cross-linking and nanoparticles introduction. Coatings with variable properties were tested for their hemocompatibility in the cone-plate tester under dynamic conditions. The obtained results enable the understanding of how substrate properties modulate PEMs interaction with blood plasma proteins and the morphotic elements.

Synthetic Paper Separates Plasma from Whole Blood with Low Protein Loss.

The separation of plasma from whole blood is the first step in many diagnostic tests. Point-of-care tests often rely on integrated plasma filters, but protein retention in such filters limits their performance. Here, we investigate plasma separation on interlocked micropillar scaffolds ("synthetic paper") by the local agglutination of blood cells coupled with the capillary separation of the plasma. We separated clinically relevant volumes of plasma with high efficiency in a separation time on par with that of state of the art techniques. We investigated different covalent and noncovalent surface treatments (PEGMA, HEMA, BSA, O2 plasma) on our blood filter and their effect on protein recovery and identified O2 plasma treatment and 7.9 μg/cm2 agglutination antibody as most suitable treatments. Using these treatments, we recovered at least 82% of the blood plasma proteins, more than with state-of-the-art filters. The simplicity of our device and the performance of our approach could enable better point-of-care tests.

Physiological and biochemical response of broiler chickens to amino acids administration

The main objective of this study was to evaluate the effect of amino acids supplementation to drinking water of meat-type broiler chickens on their blood parameters and productive traits. A total of sixty one day old, unsexed broiler chicks were obtained from a local hatchery. They were divided into three treatment groups: control group, and two treatment groups supplemented (via drinking water) with amino acids preparation (Amino-2500 USA Premium Nutrition) at 0.5 and 1.0 g/L, respectively. All chicks were fed a commercial low protein diet containing 19% crude protein and 2900 kcal metabolizable energy per kilogram of the diet. Chicks of the control group was fed the recommended (standard) diet containing 23%crude protein and 3000 kcal of ME/Kg. The duration of the experiment was five weeks. The criteria of productive and physiological responses were live body weight, weight gain, blood plasma protein fractions, plasma lipids (cholesterol, triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL). Transaminase (ALT and AST) activity indicative of liver function was measured. Kidney function test in terms of plasma creatinine, urea nitrogen and uric acid were also determined. Results showed that live body weight and weight gain of broiler chickens were significantly increased by AA administration either at three or five weeks of age. At marketing age (5 weeks), birds from the 3rd and 2nd groups achieved heavier body weigh by 32.3 and 26.8% more than the control chickens. Blood plasma total protein, albumin and globulin levels were significantly increased in the AA treatment groups for T3 and T2, respectively as compared to the control chicks. Addition of AA resulted in an obvious increase in the activity of ALT and AST indicative of negative influence of excess AA on livers function-related enzymes, especially with the higher dose of AA (T3).This was also observed for plasma uric acids and creatinine concentrations as end products of protein metabolism. The histological sections from lymphoid organs revealed better histological appearance indicative of better immunity and bird's health. It is concluded that excessive AA administration for broilers fed on low protein diet, could be used to increase live body weight, enhance protein metabolism without negative impacts on blood biochemistry, and improve their immune response. However, further study is needed to assess the cost and the net revenue from AA supplementation.

Arterial hypertension prevention as an actual medical and social problem

Social changes, technological re-equipment, intensive formation of urban infrastructure have led to a constant increase in stress factors and an excessive growth of the nervous and psychological population burden. As a result of these processes in economically developed countries, acute diseases are becoming less and less significant, unlike the group of chronic disorders, such as arterial hypertension. Data from the review of the literature and the data we have received indicate that there is an increase in the level of cortisol in the blood in the phase of anxiety, which reduces in the resistance phase. A significant role is played by another hormone - insulin, which plays a key role in the development of the general adaptive syndrome. Through it the body implements numerous counter-defects in relation to the regulatory influence of catecholamines and cortisol. In conditions of prolonged stress, the level of insulin in the blood decreases and diabetes develops. The effect of cortisol and catecholamines in the resistance phase persists. The level of oxidative modification of blood plasma proteins indices depends on the behavior of the individual and changes in his psycho-emotional state, while a prolonged increase in the levels of catecholamines and cortisol in peripheral blood causes the development of psychosomatic pathology. It is proved that under the influence of complex action of risk factors there are significant changes in the psycho-emotional state that cause hypertension. This is confirmed by the presence of the highest level of reactive anxiety in patients with hypertension of the 1st stage on the background of the lowest personal anxiety which is the basis for the occurrence of the disease. With the progression of hypertension there are more profound changes in the personality of the patient, which is accompanied by the accumulation of personal anxiety, which can lead to a depressive state of neurotic genesis, which we observed with its complication. On the basis of a comprehensive study, the effect of stress on the occurrence of a syndrome of psychoemotional stress is shown, which leads to a steady increase in blood pressure - hypertension, and with its subsequent action complicates its course.
 Bangladesh Journal of Medical Science Vol.19(4) 2020 p.722-729

In Vitro Investigation of Hemocompatibility of Hydrothermally Treated Titanium and Titanium Alloy Surfaces.

For decades, titanium and its alloys have been established as a biocompatible material for cardiovascular medical devices such as heart valves, stents, vascular grafts, catheters, etc. However, thrombosis is one of the reasons for implant failure, where blood clot forms on the implant surface, thus obstructing the flow of the blood and that leads to some serious complications. Various surface modification techniques such as heparin modification, albumin coating, surface anodization, plasma etching, and hydrothermal treatments have been explored to improve the hemocompatibility of titanium-based materials. However, there are several limitations related to the robustness of the surfaces and long-term efficacy in vivo. In this study, titanium and its alloy Ti–6Al–4V were hydrothermally treated to form nanostructured surfaces with the aim to enhance their hemocompatibility. These modified surfaces were characterized for their wettability, surface morphology, surface chemistry, and crystallinity. The hemocompatibility of these surfaces was characterized by evaluating blood plasma protein adsorption, platelet adhesion and activation, platelet–leukocyte complex formation, and whole blood clotting. The results indicate lower fibrinogen adsorption, cell adhesion, platelet activation, and whole blood clotting on hydrothermally treated surfaces. Thus, these surfaces may be a promising approach to prevent thrombosis for several titanium blood-contacting medical devices.

Filter-Membrane-Based Ultrafiltration Coupled with Surface-Enhanced Raman Spectroscopy for Potential Differentiation of Benign and Malignant Thyroid Tumors from Blood Plasma.

ObjectiveThe objective of this study is to evaluate the performance and feasibility of surface-enhanced Raman spectroscopy coupled with a filter membrane and advanced multivariate data analysis on identifying and differentiating benign and malignant thyroid tumors from blood plasma.Patients and MethodsWe proposed a membrane filter SERS technology for the differentiation between benign thyroid tumor and thyroid cancer. That is to say, by using filter membranes with optimal pore size, the blood plasma samples from thyroid tumor patients were pretreated with the macromolecular proteins being filtered out prior to SERS measurement. The SERS spectra of blood plasma ultrafiltrate obtained using filter membranes from 102 patients with thyroid tumors (70 thyroid cancers and 32 benign thyroid tumors) were then analyzed and compared. Two multivariate statistical analyses, principal component analysis-linear discriminate analysis (PCA-LDA) and Lasso-partial least squares-discriminant analysis (Lasso-PLS-DA), were performed on the SERS spectral data after background subtraction and normalization, as well as the first derivative processing, to analyze and compare the differential diagnosis of benign thyroid tumors and thyroid cancer.ResultsSERS measurements were performed in blood plasma acquired from a total of 102 thyroid tumor patients (benign thyroid tumor N=32; thyroid cancer N=70). By using filter membranes, the macromolecular proteins in blood plasma were effectively filtered out to yield high-quality SERS spectra. 84.3% discrimination accuracy between benign and malignant thyroid tumor was achieved using PCA-LDA method, while Lasso-PLS-DA yields a discrimination accuracy of 90.2%.ConclusionOur results demonstrate that SERS spectroscopy, coupled with ultrafiltration and multivariate analysis has the potential of providing a non-invasive, rapid, and objective detection and differentiation of benign and malignant thyroid tumors.

Interactions of Ionophoric Polyphenols with Human Serum Albumin

The distribution of a drug is determined, at least in part, by its interactions with serum proteins. Human serum albumin (HSA), the most abundant blood plasma protein, serves as the most common mode of transport for drugs to their target. In our previous work, we have synthesized and studied important characteristics of a series of ionophoric polyphenols as potential anti‐Alzheimer’s disease agents. As part of our ongoing investigations on the biological activity of these compounds, we are now exploring possible transport mechanisms. In our current work, the interactions of the ionophoric polyphenols with HSA were studied via in vitro and in silico methods. In line with in vitro studies, the interaction of the ionophoric polyphenols with HSA were studied by fluorescence and circular dichroism (CD) spectroscopies to obtain binding affinities, bimolecular quenching constants, theoretical number of binding sites and HSA secondary structural changes. Moreover, in line with in silico studies, a preferred mode of binding was predicted by molecular docking and the predicted systems were subject to a 5 ns MD simulation; consequently, RMSD studies were performed to attest for stability of the systems, MM/GBSA binding free energies were calculated to correlate with experimental binding affinities and per‐residue energy decomposition analyses were carried out to analyze residues critical to binding. Using resveratrol, a polyphenolic compound which has demonstrated strong neuroprotective and anti‐Alzheimer disease properties, as a control, in vitro results showed the formation of adducts (static quenching), one theoretical binding site, binding constants (Ka) ranging 104 to 106 M−1 and only slight secondary structure modifications between HSA and the ionophoric polyphenols. Further, in silico results revealed the ionophoric polyphenols and resveratrol favorably binding subdomain IIA of HSA, forming critical interactions to Trp 214 and Asp451. RMSD studies showed the HSA‐IIA system plateauing after a short time indicating stable binding events; in addition, a Pearson correlation coefficient of R=0.80 between the experimental binding affinity and computational binding free energies showed a strong correlation between in vitro and in silico results. Overall, our results seem to indicate that there is a ionophoric polyphenol‐serum albumin interaction, which could have a potential impact on the use of ionophoric polyphenols as therapeutics for Alzheimer’s disease.Support or Funding InformationThis research used resources of the National Energy Research Scientific Computing Center (NERSC), a U.S. Department of Energy Office of Science User Facility operated under Contract No. DE‐AC02‐05CH11231.

Histological Characterizations of the Brain Vascular Hyalinosis in Patients with Systemic Hypertension‐Induced Ischemic Stroke

BackgroundIschemic stroke is a major cause of death among patients with systemic hypertension. The narrowing of the brain vascular lumen increases the incidence of stroke and the formation of hyalinosis lesion is an irreversible process that occurs in the late stage of the disease and contributes to the vascular narrowing and stroke. Understanding pathologic mechanisms of brain vascular hyalinosis, thus, should contribute to the development of new therapeutic agents that inhibits and/or reverse the formation of hyalinosis, thereby reducing the incidence of ischemic stroke. Despite the clinical importance of this lesion, properties of brain vascular hyalinosis have not been well investigated. Thus, the present study performed detailed histological examinations of the hyalinosis lesions of postmortem brain vascular tissues of human patients who died of ischemic stroke due to systemic hypertension.Methods & ResultsHematoxylin and eosin staining, as well as periodic acid‐Schiff staining, showed the presence of vascular hyalinosis in patient brain tissues. In these lesions, the protein organization of the extracellular matrix was changed, the number and size of smooth muscle cells were altered, and plasma proteins, such as apolipoprotein E and fibrin, infiltrated into the vessel wall. Signs of oxidative stress and lipid peroxidation were also found. These changes are pronounced at the loci of the infiltration of the vessel walls by ApoE. We found increased number of vasa vasorum in adventitia of the small arteries. The formation and deposition of hyaline occur both from the side of the lumen of the artery and from the side of the vase vasorum. Transmission electron microscopy showed that with the development of hyalinosis, the number of smooth muscle cells that undergo atrophy. The deposition of proteins in the arterial wall is also associated with the degree of damage to endothelial cells in the lumen of the vessel and in the vasa vasorum.ConclusionsThese results demonstrate that, at the beginning of the development of hyalinosis, smooth muscle cells and vasa vasorum are increased. This process seem to involve oxidative stress, which damages endothelial cells both in the lumen of the arteries and in the vasorum vase and contributes to the infiltration of blood plasma proteins into the vascular wall. The resulting hyalinosis decreases the lumen of the arteries and increases the incidence of stroke.Support or Funding InformationSupported by NIH