Structure Of Human Serum Albumin Research Articles

Biological activity and biomolecule interaction of pyridyl thiazole derivative and its copper complex

This article discusses the synthesis of pyridyl thiazole derivative (PT) and its copper complex (PTC − Pyridyl Thiazole Copper Complex) for studies related to biological activities and biomolecule interaction. Synthesized compounds were characterized, and their biological activities were tested. The metal complex, PTC exhibited positive antibacterial and anticancer activity. The complex PTC inhibited MCF-7 cells at IC50 of 516 µg/mL as compared to the ligand PT which showed IC50 of 868 µg/mL. The PT ligand showed inhibition of S. aureus with a minimum inhibitory concentration (MIC) of 50 µg/mL. While PTC exhibited inhibition against both S. aureus and E. coli organisms with MIC of 50 µg/mL and 150 µg/mL respectively. The binding interaction of two important biomolecules such as Human Serum Albumin (HSA) and Deoxyribonucleic acid (DNA) with both free ligand and metal complex were studied to determine the type and nature of reaction and forces involved in the process. The Ksv values obtained from fluorescence experiments to determine the interaction of PT/PTC with HSA illustrated a static quenching mechanism. Circular dichroism analysis showed minor changes in α-helix percentage, suggesting a lesser influence of these compounds on the secondary structure of HSA. Molecular docking demonstrated a binding pose for PTC with ΔG = −7.51 kcal/mol, supporting the experimental findings in this study. PTC showed more strong interaction with DNA compared to the ligand. Results obtained depict that the PTC complex may have the potential to be used in cancer treatments and antibacterial applications.

Influence of para-substituted benzaldehyde derivatives with different push/pull electron strength groups on the conformation of human serum albumin and toxicological effects in zebrafish

Excessive intake of benzaldehyde and its derivatives can cause irreversible damage to living organisms. Hence, benzaldehyde derivatives with different para-substitutions of push/pull electronic groups were chosen to investigate the effect of different substituent properties on the structure of human serum albumin (HSA). The binding constants, number of binding sites, major interaction forces, protein structural changes, and binding sites of benzaldehyde (BzH) and its derivatives (4-BzHD) with HSA in serum proteins were obtained based on multispectral and molecular docking techniques. The mechanism of BzH/4-BzHD interaction on HSA is mainly static quenching and is accompanied by the formation of a ground state complex. BzH/4-BzHD is bound to HSA in a 1:1 stoichiometric ratio. The interaction forces for the binding of BzH/4-BzHD to HSA are mainly hydrogen bonding and hydrophobic interaction, which are also accompanied by a small amount of electrostatic interactions. The effect of BzH/4-BzHD on HSA conformation follows: 4-Diethylaminobenzaldehyde (4-DBzH) > 4-Nitrobenzaldehyde (4-NBzH) > 4-Hydroxybenzaldehyde (4-HBzH) > 4-Acetaminobenzaldehyde (4-ABzH) > BzH, which means that the stronger push/pull electronic strength of the para-substituted benzaldehyde derivatives has a greater effect on HSA conformation. Furthermore, the concentration-lethality curves of different concentrations for BzH/4-BzHD on zebrafish verified above conclusion. This work provides a scientific basis for the risk assessment of benzaldehyde and its derivatives to the ecological environment and human health and for the environmental toxicological studies of benzaldehyde derivatives with different strengths of push/pull electron substitution.

Structural and Mechanistic Insights into the Transport of Aristolochic Acids and their Active Metabolites by Human Serum Albumin

Aristolochic acids I and II (AA-I/II) are carcinogenic principles of Aristolochia plants, which have been employed in traditional medicinal practices and discovered as food contaminants. While the deleterious effects of AAs are broadly acknowledged, there is a dearth of information to define the mechanisms underlying their carcinogenicity. Following bioactivation in the liver, N-hydroxyaristolactam and N-sulfonyloxyaristolactam metabolites are transported via circulation and elicit carcinogenic effects by reacting with cellular DNA. In this study, we apply DNA adduct analysis, X-ray crystallography, isothermal titration calorimetry (ITC) and fluorescence quenching to investigate the role of human serum albumin (HSA) in modulating AA carcinogenicity. We find that HSA extends the half-life and reactivity of N-sulfonyloxyaristolactam-I with DNA, thereby protecting activated AAs from heterolysis. Applying novel pooled plasma HSA crystallization methods, we report high-resolution structures of myristic acid-enriched HSA (HSAMYR) and its AA complexes (HSAMYR/AA-I and HSAMYR/AA-II) at 1.9 Å resolution. Whereas AA-I is located within HSA subdomain IB, AA-II occupies subdomains IIA and IB. ITC binding profiles reveal two distinct AA sites in both complexes with association constants of 1.5 and 0.5 · 106 M-1 for HSA/AA-I versus 8.4 and 9.0 · 105 M-1 for HSA/AA-II. Fluorescence quenching of the HSA Trp214 suggests variable impacts of fatty acids on ligand binding affinities. Collectively, our structural and thermodynamic characterizations yield significant insights into AA binding, transport, toxicity, and potential allostery, critical determinants for elucidating the mechanistic roles of HSA in modulating AA carcinogenicity.

Evaluating the biomolecular interaction between delamanid/formulations and human serum albumin by fluorescence, CD spectroscopy and SPR: Effects on protein conformation, kinetic and thermodynamic parameters

Delamanid is an anti-tuberculosis drug used for the treatment of drug-resistant tuberculosis. Since delamanid has a high protein bound potential, even patients with low albumin levels should experience high and rapid delamanid clearance. However, the interaction between delamanid and albumin should be better controlled to optimize drug efficacy. This study was designed to evaluate the binding characteristics of delamanid to human serum albumin (HSA) using various methods: fluorescence spectroscopy, circular dichroism (CD), surface plasmon resonance (SPR), and molecular docking simulation. The fluorescence emission band without any shift indicated the interaction was not affected by the polarity of the fluorophore microenvironment. The reduction of fluorescence intensity at 344nm was proportional to the increment of delamanid concentration as a fluorescence quencher. UV-absorbance measurement at the maximum wavelength (λmax, 280nm) was evaluated using inner filter effect correction. The HSA conformation change was explained by the intermolecular energy transfer between delamanid and HSA during complex formation. The study, which was conducted at temperatures of 298K, 303K, and 310K, revealed a static quenching mechanism that correlated with a decreased of bimolecular quenching rate constant (kq) and binding constant (Ka) at increased temperatures. The Ka was 1.75–3.16 × 104M−1 with a specific binding site with stoichiometry 1:1. The negative enthalpy change, negative entropy change, and negative Gibbs free energy change demonstrated an exothermic-spontaneous reaction while van der Waals forces and hydrogen bonds played a vital role in the binding. The molecular displacement approach and molecular docking confirmed that the binding occurred mainly in subdomain IIA, which is a hydrophobic pocket of has, with a theoretical binding free energy of −9.33kcal/mol. SPR exhibited a real time negative sensorgram that resulted from deviation of the reflex angle due to ligand delamanid-HSA complex forming. The binding occurred spontaneously after delamanid was presented to the HSA surface. The SPR mathematical fitting model revealed that the association rate constant (kon) was 2.62 × 108s−1M−1 and the dissociation rate constant (koff) was 5.65 × 10−3 s−1M−1. The complexes were performed with an association constant (KA) of 4.64 × 1010 M−1 and the dissociation constant (KD) of 2.15 × 10−11 M. The binding constant indicated high binding affinity and high stability of the complex in an equilibrium. Modified CD spectra revealed that conformation of the HSA structure was altered by the presence of delamanid during preparation of the proliposomes that led to the reduction of secondary structure stabilization. This was indicated by the percentage decrease of α-helix. These findings are beneficial to understanding delamanid-HSA binding characteristics as well as the drug administration regimen.

Protein coupled thionine acetate probed silica nanoparticles: An integrated laser-assisted therapeutic approach for treating cancer

Herein, we report a multifaceted nanoformulation, developed by binding thionine acetate (TA) in silica matrix to form TA loaded silica nanoparticles (STA Nps), which were characterized using various physicochemical techniques. STA NPs were spherical shaped having size 40–50 nm and exhibited good heating efficiency, improved photostability and singlet oxygen production rate than TA alone. In PDT experiment, the rate of degradation for ABDMA was enhanced from 0.1367 min−1 for TA alone to 0.1774 min−1 for STA Nps, depicting an increase in the reactive oxygen species (ROS) generation ability of STA Nps. Further, the cytotoxicity of STA Nps was investigated by carrying out the biophysical studies with Calf thymus DNA (Ct-DNA) and Human Serum Albumin (HSA). The results indicated that the binding of STA Nps to Ct-DNA causes alterations in the double helix structure of DNA and as a result, STA Nps can impart chemotherapeutic effects via targeting DNA. STA Nps showed good binding affinity with HSA without compromising the structure of HSA, which is important for STA Nps sustainable biodistribution and pharmacokinetics. Based on this study, it is suggested that because of the synergistic effect of chemo and phototherapy, STA Nps can be extensively utilized as potential candidates for treating cancer.

Spectroscopic and in silico characterization of the interaction between synthetic 2-substituted-naphtho-1,4-quinones and human serum albumin

The intermolecular interaction between 2-(N-phenyl-N-methyl)aminonaphtho-1,4-quinone (1) and 2-(4-N-methylaminophenyl)naphtho-1,4-quinone (2) and human serum albumin (HSA) was investigated using spectroscopic techniques combined with in silico calculations via molecular docking. Steady-state titration of HSA fluorescence by 1 and 2 (λexc 295 nm) in PBS at 305, 310, and 315 K, as well as studies employing time-resolved fluorescence emission, demonstrated that the HSA:1 and HSA:2 interaction occurs through a static quenching mechanism. The Stern-Volmer constant (Ksv) values, (1.56 ± 0.08) and (3.05 ± 0.10) × 104 L/mol at 310 K for HSA:1 and HSA:2, respectively, indicate a moderate binding affinity. Van't Hoff plots showed that HSA:1 and HSA:2 interactions are spontaneous (negative ΔGo) with a hydrophobic character (ΔSo value of 0.00707 ± 0.00106 and 0.0392 ± 0.0062 kJ/mol K for HSA:1 and HSA:2, respectively) and specific electrostatic interactions (ΔHo value of –22.7 ± 3.3 and −14.4 ± 1.9 kJ/mol for HSA:1 and HSA:2, respectively). Synchronous fluorescence results showed significant perturbation in the microenvironment of the tryptophan residue (Trp-214). Circular dichroism indicated that after interaction with naphthoquinones 1 and 2, the HSA structure remains predominantly in the α-helix form. Finally, molecular docking revealed the formation of hydrophobic, electrostatic, and hydrogen bond interactions with the surrounding amino acid residues in subdomain IIA of HSA, which contains the Trp-214 residue, validated with the experimental drug-displacement assays. Overall, spectroscopic and in silico characterization of HSA:1 and HSA:2 might reflect in a low half-life in the human bloodstream, indicating the necessity of methods to improve the bioavailability, e.g., studies on the type of administration (oral versus intravenous).

Spectroscopic investigation and structural simulation in human serum albumin with hydroxychloroquine/Silybum marianum and a possible potential COVID-19 drug candidate.

In this study, the interaction between human serum albumin (HSA) and the hydroxychloroquine/Silybum marianum (HCQ/SM) mixture was investigated using various techniques. The observed high binding constant (Kb) and Stern-Volmer quenching constant (KSV) indicate a strong binding affinity between the HCQ/SM mixture and HSA. The circular dichroism (CD) analysis revealed that HCQ/SM induced conformational changes in the secondary structure of HSA, leading to a decrease in the α-helical content. UV-Vis analysis exhibited a slight redshift, indicating that the HCQ/SM mixture could adapt to the flexible structure of HSA. The experimental results demonstrated the significant conformational changes in HSA upon binding with HCQ/SM. Theoretical studies were carried out using molecular dynamics simulation via the Gromacs simulation package to explore insights into the drug interaction with HSA-binding sites. Furthermore, molecular docking studies demonstrated that HCQ/SM-HSA exhibited favorable docking scores with the receptor (5FUZ), suggesting a potential therapeutic relevance in combating COVID-19 with a value of -6.24 kcal mol-1. HCQ/SM exhibited stronger interaction with both SARS-CoV-2 virus main proteases compared to favipiravir. Ultimately, the experimental data and molecular docking analysis presented in this research offer valuable insights into the pharmaceutical and biological properties of HCQ/SM mixtures when interacting with serum albumin.

Structure of Human Serum Albumin at a Foam Surface.

Proteins can be adsorbed on the air-water interface (AWI), and the structural changes in proteins at the AWI are closely related to the foaming properties of foods and beverages. However, how these structural changes in proteins at the AWI occur is not well understood. We developed a method for the structural assessment of proteins in the foam state using hydrogen/deuterium exchange mass spectrometry. Adsorption sites and structural changes in human serum albumin (HSA) were identified in situ at the peptide-level resolution. The N-terminus and the loop (E492-T506), which contains hydrophobic amino acids, were identified as adsorption sites. Both the structural flexibility and hydrophobicity were considered to be critical factors for the adsorption of HSA at the AWI. Structural changes in HSA were observed after more than one minute of foaming and were spread widely throughout the structure. These structural changes at the foam AWI were reversible.

Effects of ultraviolet radiation and reactive oxygen species on the structure and ligand-binding ability of human serum albumin for norfloxacin

To explore the influence of ultraviolet radiation (UV) and reactive oxygen species (ROS) on the structure and ligand-binding ability of human serum albumin (HSA) for norfloxacin (NFLX), HSA was treated with UV (HSAUV) and UV/H2O2 (HSAUV/H2O2), respectively. The structure difference of HSA, HSAUV and HSAUV/H2O2 were investigated by Fourier transform infrared, fluorescence (i.e., emission fluorescence, synchronous fluorescence and fluorescence lifetime) and circular dichroism spectroscopy. The intermolecular interactions of HSA, HSAUV and HSAUV/H2O2 with NFLX were studied at pH 7.4 and temperatures 291, 310, and 318 K, using fluorescence emission and synchronous fluorescence spectroscopy, and combined with molecular docking. The results suggested that UV and ROS could destroy the α-helix of HSA and induce the loose of HSA structure, and the average fluorescence lifetimes of HSA decreased from 6.12 ns to 3.76 ns (HSAUV) and 3.40 ns (HSAUV/H2O2). The conformational changes of HSA caused by UV and ROS allowed NFLX to get access to more potential binding sites and promoted the binding affinity of HSA for NFLX, while the temperature stability of the HSA-NFLX complex significantly decreased. The results are useful and valuable for evaluating the protein damage caused by UV and ROS in organisms.

A comprehensive investigation of the interactions of human serum albumin with polymeric and hybrid nanoparticles.

Nanoparticles (NPs) engineered as drug delivery systems continue to make breakthroughs as they offer numerous advantages over free therapeutics. However, the poor understanding of the interplay between the NPs and biomolecules, especially blood proteins, obstructs NP translation to clinics. Nano-bio interactions determine the NPs' in vivo fate, efficacy and immunotoxicity, potentially altering protein function. To fulfill the growing need to investigate nano-bio interactions, this study provides a systematic understanding of two key aspects: (i) protein corona (PC) formation and (ii) NP-induced modifications on protein's structure and stability. A methodology was developed by combining orthogonal techniques to analyze both quantitative and qualitative aspects of nano-bio interactions, using human serum albumin (HSA) as a model protein. Protein quantification via liquid chromatography-mass spectrometry, and capillary zone electrophoresis (CZE) clarified adsorbed protein quantity and stability. CZE further unveiled qualitative insights into HSA forms (native, glycated HSA and cysteinylated), while synchrotron radiation circular dichroism enabled analyzing HSA's secondary structure and thermal stability. Comparative investigations of NP cores (organic vs. hybrid), and shells (with or without polyethylene glycol (PEG)) revealed pivotal factors influencing nano-bio interactions. Polymeric NPs based on poly(lactic-co-glycolic acid) (PLGA) and hybrid NPs based on metal-organic frameworks (nanoMOFs) presented distinct HSA adsorption profiles. PLGA NPs had protein-repelling properties while inducing structural modifications on HSA. In contrast, HSA exhibited a high affinity for nanoMOFs forming a PC altering thereby the protein structure. A shielding effect was gained through PEGylation for both types of NPs, avoiding the PC formation as well as the alteration of unbound HSA structure.

Bisphenol a modification and how its structure influences human serum albumin binding force

Bisphenol A (BPA) is an environmental hormone with substantial physiological toxicity to the human body. Three electron-withdrawing derivatives of BPA are synthesized in this study to reduce its toxicity. The interaction mechanism between BPA and its three derivatives with human serum albumin (HSA) is investigated using molecular docking, electrochemistry, circular dichroism spectrum analysis, and fluorescence spectroscopy. Temperature-dependent tests and time-resolved fluorescence spectra reveal that all four compounds dynamically quench the internal fluorescence of HSA. Based on molecular docking and site competition outcomes, four compounds are primarily bound to site I's active pocket. Thermodynamic parameters indicate that the compounds’ interaction with HSA is spontaneous, and introducing weak electron-withdrawing groups changes the action force. Circular dichroism and synchronous fluorescence measurements suggest four compounds impact HSA's structure. The substituents' electron attraction capacity determines their impact. Electrochemical studies examine the effect of electron-absorbing groups on the BPA and HSA binding capacity. Pharmacokinetics showed that nitro-substituted BPA may be a potential superior substitute for BPA. These results indicate crucial practical value, providing theoretical support for future research.

Exploring the molecular basis of tucatinib interaction with human serum albumin: A spectroscopic and computational analysis

This study delves into the kinetics of interaction among anticancer drug tucatinib (TCT) and human serum albumin (HSA), a pivotal protein that transports substances in the bloodstream of humans. Employing biophysical techniques alongside in-silico approaches, the TCT-HSA complex formation is substantiated. This binding interaction is unequivocally confirmed by the inverse relationship between temperature and Stern-Volmer constant (KSV) and the hyperchromicity in UV–visible spectra. The binding constant (Kb) value (5.34 x 104 M−1) indicates a moderate affinity between TCT and HSA, with thermodynamic analysis pointing towards stabilization through hydrogen bonds and hydrophobic and van der Waals interactions. Moreover, despite causing alterations in the vicinity of Tyr and Trp amino acids, the introduction of TCT to HSA confers a substantial protective effect against the thermal denaturation of the protein. Circular dichroism unveils a decrease in the content of alpha helices upon TCT binding. At the same time, CD thermal analysis hints at a marginal increase in the melting temperature of HSA, indicating heightened stability at elevated temperatures. Molecular docking and competitive displacement assays confirm that the preferred binding site for TCT is subdomain IIA (Sudlow's site I) of HSA. Molecular dynamics simulations emphasize the stability of the TCT-HSA complex. This work sheds light on a detailed characterization of the HSA-TCT interaction, elucidating binding mechanisms and their consequential impact on HSA structure and stability.

Insights into interaction of triazine herbicides with three kinds of different alkyl groups (simetryne, ametryn and terbutryn) with human serum albumin via multi-spectral analysis

In this study, the interaction of triazine herbicides with three kinds of different alkyl groups (simetryne, ametryn and terbutryn) with human serum albumin (HSA) are investigated through UV–vis, fluorescence, and circular dichroism (CD) spectra. The mechanisms on the fluorescence quenching of HSA initiated by triazine herbicides are obtained using Stern-Volmer, Lineweaver-Burk and Double logarithm equations. The quenching rate constant (Kq), Stern-Volmer quenching constant (Ksv), binding constant (KA), thermodynamic parameters such as enthalpy change (∆H), entropy change (∆S) and Gibbs free energy (∆G) and number of binding site (n) are calculated and compared. The variations in the microenvironment of amino acid residues are studied by synchronous fluorescence spectroscopy. The binding sites and subdomains are identified using warfarin and ibuprofen as site probes. The conformational changes of HSA are measured using CD spectra. The results reveal that the triazine herbicides with different alkyl groups can interact with HSA by static quenching. The combination of the three herbicides and HSA are equally proportional, and the binding processes are spontaneous. Hydrophobic interaction forces play important roles in simetryne-HSA and ametryn-HSA, while the interaction of terbutryn-HSA is Van der Waals forces and hydrogen bonding. Moreover, the three herbicides can bind to HSA at site I (sub-domain IIA) more than site II (subdomain IIIA), and combine with tryptophan (Trp) more easily than tyrosine (Tyr) residues, respectively. By comparison, the order of interaction strength is terbutryn-HSA > ametryn-HSA > simetryne-HSA. Terbutryn can destroy the secondary structure of HSA more than simetryne and ametryn, and the potential toxicity of terbutryn is higher. It is expected that the interactions of triazine herbicides with HSA via multi-spectral analysis can offer some valuable information for studying the toxicity and the harm of triazine herbicides on human health at molecular level in life science.

Investigating the Impact of First-Line Anti-Tuberculosis Drugs Encapsulated in a Eugenol-Based Nanoemulsion on Human Serum Albumin.

Eugenol exhibits broad-spectrum antibacterial and anti-inflammatory properties. However, cytotoxicity at high concentrations limits the full utilization of eugenol-based drug complexes. Formulations of multidrug-loaded eugenol-based nanoemulsions have reduced cytotoxicity; however, it remains crucial to understand how these eugenol complexes interact with primary human carrier proteins to design and develop therapeutic alternatives. Consequently, this study primarily aims to investigate the impact on Human Serum Albumin (HSA) when it interacts with eugenol-based complexes loaded with first-line anti-tuberculosis drugs. This study used various spectroscopic such as UV-visible spectroscopy, Fluorescence spectroscopy, Fourier-transform infrared spectroscopy and computational methods such as molecular docking and 100 ns molecular simulation to understand the impact of eugenol-based first-line anti-tuberculosis drug-loaded nanoemulsions on HSA structure. The binding of the HSA protein and eugenol-based complexes was studied using UV-visible spectroscopic analysis. Minor changes in the fluorophores of the protein further confirmed binding upon interaction with the complexes. The Fourier-transform infrared spectra showed no significant changes in protein structure upon interaction with eugenol-based multidrug-loaded nanoemulsions, suggesting that this complex is safe for internal administration. Unlike eugenol or first-line anti-tuberculosis alone, molecular docking revealed the strength of the binding interactions between the complexes and the protein through hydrogen bonds. The docked complexes were subjected to a 100 ns molecular dynamics simulation, which strongly supported the conclusion that the structure and stability of the protein were not compromised by the interaction. From the results we could comprehend that the eugenol (EUG)-drug complex showed greater stability in HSA protein structure when compared to HSA interacting with isoniazid (INH), rifampicin (RIF), pyrazinamide (PYR), or ethambutol (ETH) alone or with EUG alone. Thus, inferring the potential of EUG-based drug-loaded formulations for a safer and efficient therapeutic use.

Prunin from Poncirus trifoliata (L.) Rafin Inhibits Aldose Reductase and Glucose-Fructose-Mediated Protein Glycation and Oxidation of Human Serum Albumin.

Diabetes complications are associated with aldose reductase (AR) and advanced glycation end products (AGEs). Using bioassay-guided isolation by column chromatography, 10 flavonoids and one coumarin were isolated from Poncirus trifoliata Rafin and tested in vitro for an inhibitory effect against human recombinant AR (HRAR) and rat lens AR (RLAR). Prunin, narirutin, and naringin inhibited RLAR (IC50 0.48-2.84 μM) and HRAR (IC50 0.68-4.88 μM). Docking simulations predicted negative binding energies and interactions with the RLAR and HRAR binding pocket residues. Prunin (0.1 and 12.5 μM) prevented the formation of fluorescent AGEs and nonfluorescent Nε-(carboxymethyl) lysine (CML), as well as the fructose-glucose-mediated protein glycation and oxidation of human serum albumin (HSA). Prunin suppressed the formation of the β-cross-amyloid structure of HSA. These results indicate that prunin inhibits oxidation-dependent protein damage, AGE formation, and AR, which may help prevent diabetes complications.

Ferried Albumin-Inspired Bioadhesive With Dynamic Interfacial Bonds for Emergency Rescue.

Emergency prehospital wound closure and hemorrhage control are the first priorities for life-saving. Majority of bioadhesives form bonds with tissues through irreversible cross-linking, and the remobilization of misalignment may cause severe secondary damage to tissues. Therefore, developing an adhesive that can quickly and tolerably adhere to traumatized dynamic tissue or organ surfaces in emergency situations is a major challenge. Inspired by the structure of human serum albumin (HSA), a branched polymer with multitentacled sulfhydryl is synthesized, then, an instant and fault-tolerant tough wet-tissue adhesion (IFA) hydrogel is prepared. Adhesive application time is just 5 s (interfacial toughness of ≈580 J m-2), and favorable tissue-adhesion is maintained after ten cycles. IFA hydrogel shows unchangeable adhesive performance after 1 month of storage based on the internal oxidation-reduction mechanism. It not only can efficiently seal various organs but also achieves effective hemostasis in models of the rat femoral artery and rabbit-ear artery. This work also proposes an effective strategy for controllable adhesion, enabling the production of asymmetric adhesives with on-demand detachment. Importantly, IFA hydrogel has sound antioxidation, antibacterial property, hemocompatibility, and cytocompatibility. Hence, the HSA-inspired bioadhesive emerges as a promising first-aid supply for human-machine interface-based health management and non-invasive wound closure.

Antioxidant and anti-inflammatory potentials of Ammodaucus leucotrichus Coss. & Durieu seeds’ extracts: In vitro and in vivo studies

Ethnopharmacological relevanceAmmodaucus leucotrichus Coss. & Durieu (Apiaceae) is traditionally used in southern Algeria as a remedy against a wide range of disease due to its health-promoting properties. Aim of the studyTo investigate anti-oxidant and anti-inflammatory potentials of plant methanolic extract and its fractions in vitro and in vivo. Materials and methodsAnti-radical activity was assessed in vitro using ABTS•+, superoxide anion (O2•-) and nitric oxide radical (•NO). Lipid peroxidation inhibition was also investigated in the linoleic acid system. Enzyme inhibition assay was performed against α-amylase and α-glucosidase. The anti-inflammatory effect of extracts was screened in vitro through thermal induction of human serum albumin, and in vivo on a skin acute inflammation model induced by λ-carrageenan paw injection, xylene and croton oil topical application. Analgesic effect was evaluated by acetic acid-induced writhing test. ResultsThe highest contents of polyphenols and flavonoids was recorded by the crude extract (77.14 ± 0.01 μg GAE/mg E and 19.59 ± 0.08 μg QE/mg E, respectively). Among the extracts, ethyl acetate extract showed a promising anti-radical activity of ABTS•+, O2•- and •NO, in addition to a remarkable inhibition activity of the tested enzymes. Meanwhile, all extracts effectively protected linoleic acid against lipid peroxidation and human serum albumin structure in thermal condition even at low concentration (0.31 mg/ml). Oral administration of 200 mg/kg of crude extract successfully inhibited acetic acid induced nociception and reduced edema formation induced by xylene and carrageenan. However, a dose-dependent manner was observed to decrease ear edema by a microscopic examination in croton oil induced acute inflammation. Nitrite and malondialdehyde levels together with catalase activity were modulated in the presence of plant-derived bioactive compounds. ConclusionsThis study showed that Ammodaucus leucotrichus is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds.

Protective effect of colchicine on albumin glycation and cellular oxidative stress: Insights into diabetic cardiomyopathy.

The present work elucidates the role of colchicine (COL) on albumin glycation and cellular oxidative stress in diabetic cardiomyopathy (DCM). Human serum albumin (HSA) was glycated with methylglyoxalin the presence of COL (2.5, 3.75, and 5 µM), whereas positive and negative control samples were maintained separately. The effects of COL on HSA glycation, structural and functional modifications in glycated HSA were analyzed using different spectroscopical andfluorescence techniques. Increased fructosamine, carbonyl, and pentosidine formation in glycated HSA samples were inhibited in the presence of COL. Structural conformation of HSA and glycated HSA samples was examined by field emission scanning electron microscopy, circular dichroism, Fourier transform infrared, and proton nuclear magnetic resonance analyses, where COL maintained both secondary and tertiary structures of HSA against glycation. Functional marker assays included ABTS•+ radical scavenging and total antioxidant activities, advanced oxidative protein product formation, and turbidimetry, which showed preserved functional properties of glycated HSA in COL-containing samples. Afterward, rat cardiomyoblast (H9c2 cell line) was treated with glycated HSA-COL complex (400 μg/mL) for examining various cellular antioxidants (nitric oxide, catalase, superoxide dismutase, and glutathione) and detoxification enzymes (aldose reductase, glyoxalase I, andII) levels. All three concentrations of COL exhibited effective anti-glycation properties, enhanced cellular antioxidant levels, and detoxification enzyme activities. The report comprehensively analyzes the potential anti-glycation and properties of COL during its initial assessment.

A Facile Access to Green Fluorescent Albumin Derivatives.

A Morita-Baylis-Hillman Adduct (MBHA) derivative bearing a triphenylamine moiety was found to react with human serum albumin (HSA) shifting its emission from the blue to the green-yellow thus leading to green fluorescent albumin (GFA) derivatives and enlarging the platform of probes for aggregation-induced fluorescent-based detection techniques. A possible interaction of MBHA derivative 7 with a lipophilic pocket within the HSA structure was suggested by docking studies. DLS experiments showed that the reaction with HSA induce a conformational change of the protein contributing to the aggregation process of GFA derivatives. The results of investigations on the biological properties suggested that GFA retained the ability of binding drug molecules such as warfarin and diazepam. Finally, cytotoxicity evaluation studies suggested that, although the MBHA derivative 7 at 0.1 μg/mL affected the percentage of cell viability in comparison to the negative control, it cannot be considered cytotoxic, whereas at all the other concentrations≥0.5 μg/mL resulted cytotoxic at different extent.

Application of Infrared Free-Electron Laser Irradiation of Protein Complexes Binding to Salen-Type Schiff Base Zn(II) Complexes Using Secondary Conformational Changes in the Proteins for the Treatment of Alzheimer’s Disease

Alzheimer’s disease causes the destruction of cranial nerve cells and is said to be caused by neuronal cell death due to the accumulation of amyloid-β protein. One method for the treatment of Alzheimer’s disease is to reduce the toxicity of the amyloid beta protein. Among the possibilities is to reduce toxicity by changing the secondary structure of the protein. In this study, the secondary structure of the protein was verified by binding a zinc complex to the protein and irradiating it with an infrared free-electron laser (IR-FEL). By binding Salen-Type zinc complexes to human serum albumin (HSA) and irradiating it with IR-FEL, structural changes were observed in the α-helix and β-sheet, the secondary structure of HSA. In addition to researching the possibility of binding zinc complexes to small proteins, docking simulations were examined. GOLD docking simulations showed that it is possible to bind zinc complexes to lysozyme (Lyz), a small protein. These results suggest that binding zinc complexes to amyloid-β and inducing a secondary conformational change through IR-FEL irradiation could be used for the treatment of Alzheimer’s disease by making the complexes lose their toxicity.