Human Serum Transferrin Research Articles

Impact of pH-Dependent Dynamics of Human Serum Proteins on Dialysis Membranes: Cryptographic Structure Assessment, Synchrotron Imaging of Membrane-Protein Adsorption, and Molecular Docking Studies

Proteins are fundamental to biochemical processes and critical in hemodialysis. This study investigates the impact of pH on human serum albumin (HSA), fibrinogen (FB), and transferrin (TRF) interactions with polyarylethersulfone (PAES) hemodialysis membranes. A multi-method approach was utilized, including protein crystallography for structural insights, hydration layer analysis to explore solvation and interaction potentials, molecular docking using AutoDock 4.0 for binding affinity simulations, and in-situ X-ray synchrotron SR-μCT imaging to observe protein deposition dynamics.Molecular docking revealed that PAES demonstrated superior binding energies and interaction patterns with FB and TRF compared to cellulose triacetate (CTA), facilitated by specific hydrogen bonding within a water shell. CTA displayed weaker, hydration-sensitive interactions varying with pH. Imaging studies indicated that FB showed higher adsorption at pH 6 than at pH 7.2, predominantly in the middle membrane regions. Similarly, HSA and TRF exhibited increased adsorption at pH 6, suggesting a stronger affinity under acidic conditions. Mixed protein solutions also indicated higher adsorption at pH 6, emphasizing an increased risk of membrane fouling.These findings highlight the crucial role of pH in modulating protein-membrane interactions and enhancing the efficacy of hemodialysis. A deeper understanding of hydration environments and their effects on protein binding affinities provides valuable insights for optimizing membrane design and performance. Clinically, this research suggests that fine-tuning pH during hemodialysis could mitigate protein fouling on membranes, thereby improving procedural efficiency and potentially leading to better patient outcomes through enhanced dialysis effectiveness.

Pegylated gold nanoparticles interact with lipid bilayer and human serum albumin and transferrin

Gold nanoparticles (AuNPs) are potentially applicable in drug/nucleic acid delivery systems. Low toxicity, high stability, and bioavailability are crucial for the therapeutic use of AuNPs and they are mainly determined by their interactions with proteins and lipids on their route to the target cells. In this work, we investigated the interaction of two pegylated gold nanoparticles, AuNP14a and AuNP14b, with human serum proteins albumin (HSA) and transferrin (Tf) as well as dimyristoyl-phosphatidylcholine (DMPC) liposomes, which can be a representative of biomembranes. We showed that AuNP14a/b interacted with HSA and Tf changing their electrical, thermodynamic, and structural properties as evidenced by dynamic light scattering, zeta potential, transmission electron microscopy, circular dichroism, fluorescence quenching, and isothermal titration calorimetry. These nanoparticles penetrated the DMPC membrane suggesting their ability to reach a target inside the cell. In most of the effects, AuNP14b was more effective than AuNP14a, which might result from its more positive charge. Further studies are needed to evaluate whether the interaction of AuNP14a/b with HSA and Tf is safe for the cell/organism and whether they may safely penetrate natural membranes.

DNA Origami Incorporated into Solid-State Nanopores Enables Enhanced Sensitivity for Precise Analysis of Protein Translocations.

The rapidly advancing field of nanotechnology is driving the development of precise sensing methods at the nanoscale, with solid-state nanopores emerging as promising tools for biomolecular sensing. This study investigates the increased sensitivity of solid-state nanopores achieved by integrating DNA origami structures, leading to the improved analysis of protein translocations. Using holo human serum transferrin (holo-hSTf) as a model protein, we compared hybrid nanopores incorporating DNA origami with open solid-state nanopores. Results show a significant enhancement in holo-hSTf detection sensitivity with DNA origami integration, suggesting a unique role of DNA interactions beyond confinement. This approach holds potential for ultrasensitive protein detection in biosensing applications, offering advancements in biomedical research and diagnostic tool development for diseases with low-abundance protein biomarkers. Further exploration of origami designs and nanopore configurations promises even greater sensitivity and versatility in the detection of a wider range of proteins, paving the way for advanced biosensing technologies.

Selective Clearance of Circulating Histones Based on Dodecapeptide-Grafted Copolymer Material for Sepsis Blood Purification.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Research indicates that circulating histones, as pathogenic factors, may represent a therapeutic target for sepsis. However, effectively clearing circulating histones poses a challenge due to their structural similarity to normal blood proteins, their low abundance in the bloodstream, and serious interference from other blood biomacromolecules. Here we design a dodecapeptide-based functional polymer that can selectively adsorb circulating histones from the blood. The peptide, named P1 (HNHHQLALVESY), was discovered through phage display screening and demonstrated a strong affinity for circulating histones while exhibiting negligible affinities for common proteins in the blood, such as human serum albumin (HSA), immunoglobulin G (IgG), and transferrin (TRF). Furthermore, the P1 peptide was incorporated into a functional polymer design, poly(PEGMA-co-P1), which was immobilized onto a silica gel surface through reversible addition-fragmentation chain transfer polymerization. The resulting material was characterized using solid nuclear magnetic resonance, thermogravimetric analysis, and X-ray photoelectron spectroscopy. This material demonstrated the ability to selectively and efficiently capture circulating histones from both model solutions and whole blood samples while also exhibiting satisfactory blood compatibility, good antifouling properties, and resistance to interference. Satisfactory binding affinity and efficient capture capacity toward histone were also observed for the other screened peptide P2 (QMSMDLFGSNFV)-grafted polymer, validating phage display as a reliable ligand screening strategy. These findings present an approach for the specific clearance of circulating histones and hold promise for future clinical applications in blood purification toward sepsis.

Polyaniline-Coated Flower-Like Titanium Dioxide Magnetic Fluorescent Imprinted Nanoparticles for the Determination of Transferrin in Human Serum

As a typical glycoprotein and potential disease biomarker, transferrin (TrF) plays an important role in binding and transporting iron ions and regulating homeostasis in vivo. However, conventional serum TrF detection technologies often need complex sample pretreatments and long analysis times. Hence, fluorescent magnetic molecular imprinted polymers (FMMIPs) were prepared for the determination of TrF in human serum, which combined the high sensitivity of fluorescence and the specificity of molecularly imprinted polymers. This material is a labor-saving, easy-to-use, and noninvasive biomarker, which provides the determination of serum TrF with high selectivity. Moreover, the preparation and fluorescent properties of FMMIPs were systematically investigated. Under the optimized conditions, the prepared FMMIPs had a good adsorption and fast response with a low relative standard deviation (less than 5%) for TrF with an imprinting factor of 3.21 and detection limit of 0.107 μg/mL. This material provides direct, sensitive, and rapid protein determination for TrF in serum.

Exploring the Specific Role of Iron Center in the Catalytic Activity of Human Serum Transferrin: CTAB-Induced Conformational Changes and Sequestration by Mixed Micelles.

Conformational changes play a seminal role in modulating the activity of proteins. This concept becomes all the more relevant in the context of metalloproteins, owing to the formation of specific conformation(s) induced by internal perturbations (like a change in pH, ligand binding, or receptor binding), which may carry out the binding and release of the metal ion/ions from the metal binding center of the protein. Herein, we investigated the conformational changes of an iron-binding protein, monoferric human serum transferrin (Fe-hTF), using several spectroscopic approaches. We could reversibly tune the cetyltrimethylammonium bromide (CTAB)-induced conformation of the protein, exploiting the concept of mixed micelles formed by three sequestrating agents: (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) hydrate (CHAPS) and two bile salts, namely, sodium cholate (NaC) and sodium deoxycholate (NaDC). The formation of mixed micelles between CTAB and these reagents (CHAPS/NaC/NaDC) results in the sequestration of CTAB molecules from the protein environment and aids the protein in reattaining its native-like structure. However, the guanidinium hydrochloride-induced denatured Fe-hTF did not acquire its native-like structure using these sequestrating agents, which substantiates the exclusive role of mixed micelles in the present study. Apart from this, we found that the conformation of transferrin (adopted in the presence of CTAB) displays pronounced esterase-like activity toward the para-nitrophenyl acetate (PNPA) substrate as compared to native transferrin. We also outlined the impact of the iron center and amino acids surrounding the iron center on the effective catalytic activity in the CTAB medium. We estimated ∼3 times higher specific catalytic efficiency for the iron-depleted Apo-hTF compared to the fully iron-saturated Fe2-hTF in the presence of CTAB.

Molecularly imprinted polymer-based SERS sensing of transferrin in human serum.

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2-MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA-Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2-MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL-1 to 1 mg mL-1 (R2 = 0.9974), and the LOD was 0.00407 ng mL-1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications.

In-situ determination of ferric ions in human blood serum using highly fluorescence nitrogen and boron co-doped carbon dots nanoprobe without serum preparation step: A direct and solvent-free method

Different methods have been reported for Fe3+ ions determination as an essential element in many physiological processes, but most of these methods suffer from the consumption of solvent and time in the blood serum sample preparation stage. In this study, we report fabrication of a selective and sensitive high fluorescent nanoprobe based on the boron and nitrogen co-doped carbon dots for Fe3+ determination in aqueous solution and human blood serum as an important biological sample. Interestingly, under mildly acidic conditions, adjusted ionic strength, and the existence of EDTA, Fe3+ ions can be released from human serum transferrin, with no need for serum protein removal process as a separate step in sample preparation. Indeed, based on the innovative approach, both steps (consisting of Fe3+ ion release of protein and its detection) are in-situ performed. Notably, limit of detection of Fe3+ was improved from 4.72 μM to 0.61 μM and linear range from 40–250 μM to 1–500 μM, after optimization of conditions. Evaluation of obtained results by proposed method, was done using atomic absorption spectroscopy. The excellent precision and accuracy of achievement results, appear that designed nanoprobe is a promising novel method for ferric ion detection in biological systems.

Low-density hepatitis C virus infectious particles are protected from oxidation by secreted cellular proteins.

Assessments of viral stability on surfaces or in body fluids under different environmental conditions and/or temperatures are often performed, as they are key to understanding the routes and parameters of viral transmission and to providing clues on the epidemiology of infections. However, for most viruses, the mechanisms of inactivation vs stability of viral particles remain poorly defined. Although they are structurally diverse, with different compositions, sizes, and shapes, enveloped viruses are generally less stable than non-enveloped viruses, pointing out the role of envelopes themselves in virus lability. In this report, we investigated the properties of hepatitis C virus (HCV) particles with regards to their stability. We found that, compared to alternative enveloped viruses such as Dengue virus (DENV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis delta virus (HDV), and Crimean-Congo hemorrhagic fever virus (CCHFV) that infect the liver, HCV particles are intrinsically labile. We determined the mechanisms that drastically alter their specific infectivity through oxidation of their lipids, and we highlighted that they are protected from lipid oxidation by secreted cellular proteins, which can protect their membrane fusion capacity and overall infectivity.

In situ synchrotron quantitative analysis of competitive adsorption tendency of human serum protein to different clinical hemodialysis membranes and assessment of potential impacts

Protein adsorption on hemodialysis (HD) membrane matrices and surfaces is a highly undesirable process, as it triggers complement activation and leads to severe health complications for HD patients. However, there is a lack of systematic research investigating the correlation between membrane characteristics and their performance in the dialysis process. This study aims to provide a comprehensive understanding of the competitive adsorption tendencies of three human serum proteins (albumin (HSA), fibrinogen (FB), and transferrin (TRF)) on clinical dialysis membranes composed of polyethersulfone (PES), polyacrylonitrile (PAN), and polyvinyl fluoride (PVDF) polymers. To assess membrane morphology across the membrane cross-section, in situ synchrotron radiation micro-computed tomography (SR-µCT) imaging was conducted at the Canadian Light Source (CLS). Protein adsorption was analyzed qualitatively and quantitatively using an innovative synchrotron-based X-ray tomography technique. To determine the mutual influence of protein species on overall protein adsorption, adsorption from single-protein solutions was compared to adsorption from a protein mixture. Regarding single-protein adsorption, the PVDF membrane exhibited 40% less adsorption of HSA compared to the PES membrane. Conversely, FB adsorption was approximately 25% higher on the PVDF membrane compared to the PES membrane. The PAN membrane showed similar levels of HSA adsorption as the PES membrane and similar levels of FB adsorption as the PVDF membrane. In the case of adsorption from the protein mixture, a suppression of HSA adsorption and replacement of HSA with FB were observed. Consequently, the initial solution with a HSA content of 92% resulted in an adsorbed layer containing approximately 75–80% HSA across all the studied membranes. TRF adsorption remained unaffected by the presence of other proteins, consistent across all three membranes. Notably, the PES membrane exhibited the most significant change in the adsorbed protein composition between single-protein and multi-protein adsorption. In addition, this study comprehensively assesses the impact of fibrinogen adsorption on dialysis, including its consequences, blood activation, and implications for quality of life.

H3nota Derivatives Possessing Picolyl and Picolinate Pendants for Ga3+ Coordination and 67Ga3+ Radiolabeling.

We synthesized, thanks to the regiospecific N-functionalization using an orthoamide intermediate, two 1,4,7-triazacyclononane derivatives containing an acetate arm and either a methylpyridine or a picolinic acid group, respectively, Hnoapy and H2noapa, as new Ga3+ chelators for potential use in nuclear medicine. The corresponding Ga3+ complexes were synthesized and structurally characterized in solution by 1H and 13C NMR. The [Ga(noapy)]2+ complex appears to exist in solution as two diasteroisomeric pairs of enantiomers, as confirmed by density functional theory (DFT) calculations, while for [Ga(noapa)]+, a single species is present in solution. Solid-state investigations were possible for the [Ga(noapa)]+ complex, which crystallized from water as a pair of enantiomers. The average length of the N-Ga bonds of 2.090 Å is identical with that found for the [Ga(nota)] complex, showing that the presence of the picolinate arm does not hinder the coordination of the ligand to the metal ion. Protonation constants of noapy- and noapa2- were determined by potentiometric titrations, providing an overall basicity ∑log KiH (i = 1-4) that increases in the order noapy- < noapa2- < nota3- with increases in the negative charge of the ligand. Stability constants determined by pH-potentiometric titrations supplemented with 71Ga NMR data show that the stabilities of [Ga(noapy)]2+ and [Ga(noapa)]+ are lower compared to that of [Ga(nota)] but higher than those of other standards such as [Ga(aazta)]-. 67Ga radiolabeling studies were performed in order to demonstrate the potential of these chelators for 67/68Ga-based radiopharmaceuticals. The labelings of Hnoapy and H2noapa were nearly identical, outperforming H3nota. Stability studies were conducted in phosphate-buffered saline and in the presence of human serum transferrin, revealing no significant decomplexation of [67Ga][Ga(noapy)]2+ and [67Ga][Ga(noapa)]+ compared to [67Ga][Ga(nota)]. Finally, all complexes were found to be highly hydrophilic, with calculated log D7.4 values of -3.42 ± 0.05, -3.34 ± 0.04, and -3.00 ± 0.23 for Hnoapy, H2noapa, and H3nota, respectively, correlating with the charge of each complex and the electrostatic potentials obtained with DFT.

Macromolecular Crowding Promotes Re-entrant Liquid-Liquid Phase Separation of Human Serum Transferrin and Prevents Surface-Induced Fibrillation.

Protein aggregation and inactivation upon surface immobilization are major limiting factors for analytical applications in biotechnology-related fields. Protein immobilization on solid surfaces often requires multi-step surface passivation, which is time-consuming and inefficient. Herein, we have discovered that biomolecular condensates of biologically active human serum transferrin (Tf) can effectively prevent surface-induced fibrillation and preserve the native-like conformation of phase-separated Tf over a period of 30 days. It has been observed that macromolecular crowding promotes homotypic liquid-liquid phase separation (LLPS) of Tf through enthalpically driven multivalent hydrophobic interactions possibly via the involvement of its low-complexity domain (residues 3-20) containing hydrophobic amino acids. The present LLPS of Tf is a rare example of salt-mediated re-entrant phase separation in a broad range of salt concentrations (0-3 M) solely via the involvement of hydrophobic interactions. Notably, no liquid-to-solid-like phase transition has been observed over a period of 30 days, suggesting the intact conformational integrity of phase-separated Tf, as revealed from single droplet Raman, circular dichroism, and Fourier transform infrared spectroscopy measurements. More importantly, we discovered that the phase-separated condensates of Tf completely inhibit the surface-induced fibrillation of Tf, illustrating the protective role of these liquid-like condensates against denaturation and aggregation of biomolecules. The cell mimicking compact aqueous compartments of biomolecular condensates with a substantial amount of interfacial water preserve the structure and functionality of Tf. Our present study highlights an important functional aspect of biologically active protein condensates and may have wide-ranging implications in cell physiology and biotechnological applications.

Cu-MOF nanosheets modified nickel foam: A versatile platform for highly sensitive electrochemical detection of transferrin in simulated human blood serum

Transferrin (TRF) is a type of glycoprotein present in blood plasma that plays a vital role in facilitating the absorption, storage, and movement of iron(III) ions within the circulatory system of multiple vertebrates. Herein, we report one-pot solvothermal synthesis of Copper Metal-Organic Framework nanosheets modified nickel foam (Cu-MOF/NF) for electrochemical detection of transferrin (TRF) in simulated human blood serum. The crystal structure of the Cu-MOF nanosheets was determined through X-ray diffraction (XRD), while Raman spectroscopy and Fourier-transform infrared spectroscopy (FTIR) analysis were employed to investigate the vibrational modes and the presence of surface OH groups, respectively. The nanosheet morphology of the Cu-MOF was observed and characterized using scanning electron microscopy (SEM) micrographs.The as-fabricated Cu-MOF/NF exhibits a sensitivity of 1.36 mA/x (x = mg.mL−1cm−2) for a linear range of concentrations from 1 mg mL−1 – 100 mg mL−1 with a low limit of detection (LOD) of 0.81 mg mL−1. The sensor exhibited good selectivity for TRF, even in the presence of interfering ions such as bovine serum albumin, ascorbic acid, uric acid, and urea, with concentrations 100-fold higher than TRF. The porous nickel foam with high conductivity, offers numerous active sites and pathways for ion transport, as well as pathways for electron transport during electrochemical catalytic reactions. This performance of the sensor is attributed to Cu 2+/Cu+ redox couple at the octahedral sites of the Cu-MOF facilitating the electro-oxidation of TRF and charge-carrier delocalization during the catalytic reaction. The as-fabricated sensor is successful in the determination of trace level TRF concentration the human blood serum with excellent recovery percentages of 108.33% This proves Cu-MOF/NF as a promising platform for various electrochemical analytical applications.

Soft molecularly imprinted nanoparticles with simultaneous lossy mode and surface plasmon multi-resonances for femtomolar sensing of serum transferrin protein

The simultaneous interrogation of both lossy mode (LMR) and surface plasmon (SPR) resonances was herein exploited for the first time to devise a sensor in combination with soft molecularly imprinting of nanoparticles (nanoMIPs), specifically entailed of the selectivity towards the protein biomarker human serum transferrin (HTR). Two distinct metal-oxide bilayers, i.e. TiO2–ZrO2 and ZrO2–TiO2, were used in the SPR–LMR sensing platforms. The responses to binding of the target protein HTR of both sensing configurations (TiO2–ZrO2–Au-nanoMIPs, ZrO2–TiO2–Au-nanoMIPs) showed femtomolar HTR detection, LODs of tens of fM and KDapp ~ 30 fM. Selectivity for HTR was demonstrated. The SPR interrogation was more efficient for the ZrO2–TiO2–Au-nanoMIPs configuration (sensitivity at low concentrations, S = 0.108 nm/fM) than for the TiO2–ZrO2–Au-nanoMIPs one (S = 0.061 nm/fM); while LMR was more efficient for TiO2–ZrO2–Au-nanoMIPs (S = 0.396 nm/fM) than for ZrO2–TiO2–Au-nanoMIPs (S = 0.177 nm/fM). The simultaneous resonance monitoring is advantageous for point of care determinations, both in terms of measurement’s redundancy, that enables the cross-control of the measure and the optimization of the detection, by exploiting the individual characteristics of each resonance.

A Novel NanoMIP-SPR Sensor for the Point-of-Care Diagnosis of Breast Cancer.

Simple, fast, selective, and reliable detection of human epidermal growth factor receptor 2 (HER2) is of utmost importance in the early diagnosis of breast cancer to prevent its high prevalence and mortality. Molecularly imprinted polymers (MIPs), also known as artificial antibodies, have recently been used as a specific tool in cancer diagnosis and therapy. In this study, a miniaturized surface plasmon resonance (SPR)-based sensor was developed using epitope-mediated HER2-nanoMIPs. The nanoMIP receptors were characterized using dynamic light scattering (DLS), zeta potential, Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and fluorescent microscopy. The average size of the nanoMIPs was determined to be 67.5 ± 12.5 nm. The proposed novel SPR sensor provided superior selectivity to HER2 with a detection limit (LOD) of 11.6 pg mL-1 in human serum. The high specificity of the sensor was confirmed by cross-reactivity studies using P53, human serum albumin (HSA), transferrin, and glucose. The sensor preparation steps were successfully characterized by employing cyclic and square wave voltammetry. The nanoMIP-SPR sensor demonstrates great potential for use in the early diagnosis of breast cancer as a robust tool with high sensitivity, selectivity, and specificity.

Glycoproteomics meets thermodynamics: A calorimetric study of the effect of sialylation and synergistic anion on the binding of iron to human serum transferrin

The thermodynamic parameters for the binding of ferric ions to human serum transferrin (hTf) as the major mediator of iron transport in blood plasma were determined by isothermal titration calorimetry in the presence of carbonate and oxalate as synergistic anions at pH 7.4. The results indicate that the binding of ferric ions to the two binding sites of hTf is driven both enthalpically and entropically in a lobe-dependent manner: binding to the C-site is mainly enthalpically driven, whereas binding to the N-site is mainly entropically driven. Lower sialic acid content of hTf leads to more exothermic apparent binding enthalpies for both lobes, while the increased apparent binding constants for both sites were found in the presence of carbonate. Sialylation also unequally affected the heat change rates for both sites only in the presence of carbonate, but not in the presence of oxalate. Overall, the results suggest that the desialylated hTf has a higher iron sequestering ability, which may have implications for iron metabolism.

Interaction of Polystyrene Nanoparticles with Supported Lipid Bilayers: Impact of Nanoparticle Size and Protein Corona.

Polystyrene is one of the most widely used plastics. This article reports on the interaction of 50 and 210nm polystyrene nanoparticles (PSNPs) with human serum albumin(HSA) and transferrin (Tf), as well as their effect on supported lipid bilayers (SLBs), using experimental and theoretical approaches. Dynamic light scattering(DLS) and atomic force microscopy(AFM) measurements showthat the increase in diameter for the PSNP-protein bioconjugates depends on nanoparticle size and type of proteins. The circular dichroism(CD) spectroscopy results demonstrate that the proteins preserve their structures when they interact with PSNPs at physiological temperatures. The quartz crystal microbalance(QCM) technique reveals that PSNPs and their bioconjugates show no strong interactions with SLBs. On the contrary, the molecular dynamics simulations(MDS) show that both proteins bind stronglyto the lipid bilayer (SLBs)when compared to their binding to a polystyrene surface model. The interaction is strongly dependent on the protein and lipid bilayer composition. Both the PSNPs and their bioconjugates show no toxicity in human umbilical vein endothelial(HUVEC) cells; however, bare 210nm PSNPs and 50nm PSNP-Tf bioconjugates show an increase in reactive oxygen species production. This study may be relevant for assessing the impact ofplasticson health.

Cisplatin Binding to Human Serum Transferrin: A Crystallographic Study.

The molecular mechanism of how human serum transferrin (hTF) recognizes cisplatin at the atomic level is still unclear. Here, we report the molecular structure of the adduct formed upon the reaction of hTF with cisplatin. Pt binds the side chain of Met256 (at the N-lobe), without altering the protein overall conformation.

Optimization of enzymatic desialylation of human serum transferrin

Optimization of enzymatic desialylation of human serum transferrin

Influence of clinical hemodialysis membrane morphology and chemistry on protein adsorption and inflammatory biomarkers released: In-situ synchrotron imaging, clinical and computational studies

Hemodialysis (HD) is often accompanied with activation of biochemical cascade reactions, caused by undesirable protein adsorption, which results in severe consequences for HD patients. Present research aims to study three hemodialysis membranes currently available in the Canadian hospitals of polyacrylonitrile (PAN), polyethersulfone (PES) and polyvinylidene fluoride (PVDF) and their interaction with three main human serum proteins: Human Serum Ablumin (HSA), Human Serum Fibrinogen (FB) and Human Serum Transferrin (TRF). In-situ synchrotron-based X-ray tomography (SR-μCT) was used to evaluate main membranes characteristics such as fiber diameter, pore size and their distribution, as well as to study the process of protein adsorption on the membranes surface and along membrane matrices. Scanning Electron Microscopy (SEM) was also used to investigate the morphology of proteins deposited on the membrane surface. Furthermore, interaction of membranes with inflammatory biomarkers was studied. Collected blood samples from HD patients were analyzed using Luminex assay for the inflammatory biomarkers of Serpin/Antitrombin-III, Properdin, C5a, 1L-1α, 1L-1β, IL-6 and TNF-α. Our results indicate the difference in the interaction of membranes with proteins is mainly attributed to a membrane surface charge and membrane chemistry. PAN and PES membranes, which are possessing high negative charge (-41.5mV and -68mV) and polar surface groups, would alter the morphology of adsorbed HAS and FB, while PVDF surface does not affect protein crystals growth. Furthermore, the molecular docking results showed that the highest interaction energy of human serum proteins was with PES membrane. The increased interaction of PES membrane with human serum proteins has triggered inflammation reactions. The release of C5a, IL-6 and Serpin cytokines for PES membrane was drastically higher compared to PAN and PVDF. The relative increase in those cytokine concentrations was 400-2000% for PES membrane, while it decreased by 10-40% for PAN and PVDF. It is worth noted that PVDF membrane had the lowest charge of -2.5 mV among investigated membranes, and it possessed the lowest interaction with human serum proteins and the least inflammation response.