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.

Exploring the interaction of a potent anti-cancer drug Selumetinib with bovine serum albumin: Spectral and computational attributes.

The binding of drugs to plasma proteins determines its fate within the physiological system, hence profound understanding of its interaction within the bloodstream is important to understand its pharmacodynamics and pharmacokinetics and thereby its therapeutic potential. In this regard, our work delineates the mechanism of interaction of Selumetinib (SEL), a potent anti-cancer drug showing excellent effect against multiple solid tumors, with plasma protein bovine serum albumin (BSA), using methods such as absorption, steady-state fluorescence, time-resolved, fluorescence resonance energy transfer, Fourier transform infrared spectra (FTIR), circular dichroism (CD), synchronous and 3D-fluorescence, salt fluorescence, molecular docking and molecular dynamic simulations. The BSA fluorescence intensity was quenched with increasing concentration of SEL which indicates interactions of SEL with BSA. Stern-Volmer quenching analysis and lifetime studies indicate the involvement of dynamic quenching. However, some contributions from the static quenching mechanism could not be ruled out unambiguously. The association constant was found to be 5.34 × 105 M-1 and it has a single binding site. The Förster distance (r) indicated probable energy transmission between the BSA and SEL. The positive entropy changes and enthalpy change indicate that the main interacting forces are hydrophobic forces, also evidenced by the results of molecular modeling studies. Conformation change in protein framework was revealed from FTIR, synchronous and 3D fluorescence and CD studies. Competitive binding experiments as well as docking studies suggest that SEL attaches itself to site I (subdomain IIA) of BSA where warfarin binds. Molecular dynamic simulations indicate the stability of the SEL-BSA complex. The association energy between BSA and SEL is affected in the presence of different metals differently.

Blood urea nitrogen to serum albumin ratio as a new prognostic indicator in type 2 diabetes mellitus patients with chronic kidney disease.

Chronic kidney disease (CKD) is often a common comorbidity in critically ill patients with type 2 diabetes mellitus (T2DM). This study explored the relationship between blood urea nitrogen to serum albumin ratio (BAR) and mortality in T2DM patients with CKD in intensive care unit (ICU). Patients were recruited from the Medical Information Mart database, retrospectively. The primary and secondary outcomes were 90-day mortality, the length of ICU stay, hospital mortality and 30-day mortality, respectively. Cox regression model and Kaplan-Meier survival curve were performed to explore the association between BAR and 90-day mortality. Subgroup analyses were performed to determine the consistency of this association. A total of 1920 patients were enrolled and divided into the three groups (BAR < 9.2, 9.2 ≤ BAR ≤ 21.3 and BAR > 21.3). The length of ICU stay, 30-day mortality, and 90-day mortality in the BAR > 21.3 group were significantly higher than other groups. In Cox regression analysis showed that high BAR level was significantly associated with increased greater risk of 90-day mortality. The adjusted HR (95%CIs) for the model 1, model 2, and model 3 were 1.768 (1.409-2.218), 1.934, (1.489-2.511), and 1.864, (1.399-2.487), respectively. Subgroup analysis also showed the consistency of results. The Kaplan-Meier survival curve analysis revealed similar results as well that BAR > 21.3 had lower 90-day survival rate. High BAR was significantly associated with increased risk of 90-day mortality. BAR could be a simple and useful prognostic tool in T2DM patients with CKD in ICU.

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.

Transfer of ANS-Like Drugs from Micellar Drug Delivery Systems to Albumin Is Highly Favorable and Protected from Competition with Surfactant by "Reserved" Binding Sites.

Micellar drug delivery systems (MDDS) for the intravenous administration of poorly soluble drugs have great advantages over alternative formulations in terms of the safety of their excipients, storage stability, and straightforward production. A classic example is mixed micelles of glycocholate (GC) and lecithin, both endogenous substances in human blood. What limits the use of MDDS is the complexity of the transitions after injection. In particular, as the MDDS disintegrate partially or completely after injection, the drug has to be transferred safely to endogenous carriers in the blood, such as human serum albumin (HSA). If this transfer is compromised, the drug might precipitate─a process that needs to be excluded under all circumstances. The key question of this paper is whether the high local concentration of GC at the moment and site of MDDS dissolution might transiently saturate HSA binding sites and, hence, endanger quick drug transfer. To address this question, we have used a new approach, which is time-resolved fluorescence spectroscopy of the single tryptophan in HSA, Trp-214, to characterize the competitive binding of GC and the drug substitute anilinonaphthalenesulfonate (ANS) to HSA. Time-resolved fluorescence of Trp-214 showed important advantages over established methods for tackling this problem. ANS has been the standard "model drug" to study albumin binding for decades, given its structural similarity to the class of naphthalene-containing acidic drugs and the fact that it is displaced from HSA by numerous drugs (which presumably bind to the same sites). Our complex global fit uses the critical approximation that the average lifetimes behave similarly to a single lifetime, but the resulting errors are found to be moderate and the results provide a convincing explanation of the, at first glance, counterintuitive behavior. Accordingly, and largely in line with the literature, we observed two types of sites binding ANS at HSA: 3 type A, rather peripheral, and 2 type B, likely more central sites. The latter quench Trp-214 by Förster Resonance Energy Transfer (FRET) with a rate constant of ≈0.4 ns-1 per ANS. Adding millimolar concentrations of GC displaces ANS from the A sites but not from B sites. At incomplete ANS saturation, this causes a GC-induced translocation of ANS from A to the more FRET-active B sites. This leads to the apparent paradox that the partial displacement of ANS from HSA increases its quenching effect on Trp-214. The most important conclusion is that (ANS-like) drugs cannot be displaced from the type-B sites, and consequently, drug transfer to these sites is not impaired by competitive binding of GC in the vicinity of a dissolving micelle. The second conclusion is that for unbound GC above the CMC (9 mM), ANS equilibrates between HSA and GC micelles but with a strong preference for free sites on HSA. That means that even persisting micelles would lose their cargo readily once exposed to HSA. For all MDDS sharing this property, targeted drug delivery approaches involving them as the nanocarrier would be pointless.

Association of Serum AGR With All-Cause and Cause-Specific Mortality Among Individuals With Diabetes.

BACKGROUND: There is insufficient data to support a link between serum AGR and mortality in individuals with diabetes. This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. METHODS: This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional hazards models. RESULTS: 2415 all-cause deaths, including 688 cardiovascular deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (Ptrend<0.0001), cardiovascular mortality (Ptrend<0.001), and cancer mortality (Ptrend<0.01) were 0.51(0.42,0.60), 0.62(0.46,0.83), and 0.57(0.39,0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per one-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P<0.001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. CONCLUSIONS: AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those under age 60 and heavy drinker.

Enhanced therapeutic potential of antibody fragment via IEDDA-mediated site-specific albumin conjugation.

BACKGROUND: The use of single-chain variable fragments (scFvs) for treating human diseases, such as cancer and immune system disorders, has attracted significant attention. However, a critical drawback of scFv is its extremely short serum half-life, which limits its therapeutic potential. Thus, there is a critical need to prolong the serum half-life of the scFv for clinical applications. One promising serum half-life extender for therapeutic proteins is human serum albumin (HSA), which is the most abundant protein in human serum, known to have an exceptionally long serum half-life. However, conjugating a macromolecular half-life extender to a small protein, such as scFv, often results in a significant loss of its critical properties. RESULTS: In this study, we conjugated the HSA to a permissive site of scFv to improve pharmacokinetic profiles. To ensure minimal damage to the antigen-binding capacity of scFv upon HSA conjugation, we employed a site-specific conjugation approach using a heterobifunctional crosslinker that facilitates thiol-maleimide reaction and inverse electron-demand Diels-Alder reaction (IEDDA). As a model protein, we selected 4D5scFv, derived from trastuzumab, a therapeutic antibody used in human epithermal growth factor 2 (HER2)-positive breast cancer treatment. We introduced a phenylalanine analog containing a very reactive tetrazine group (frTet) at conjugation site candidates predicted by computational methods. Using the linker TCO-PEG4-MAL, a single HSA molecule was site-specifically conjugated to the 4D5scFv (4D5scFv-HSA). The 4D5scFv-HSA conjugate exhibited HER2 binding affinity comparable to that of unmodified 4D5scFv. Furthermore, in pharmacokinetic profile in mice, the serum half-life of 4D5scFv-HSA was approximately 12 h, which is 85 times longer than that of 4D5scFv. CONCLUSIONS: The antigen binding results and pharmacokinetic profile of 4D5scFv-HSA demonstrate that the site-specifically albumin-conjugated scFv retained its binding affinity with a prolonged serum half-life. In conclusion, we developed an effective strategy to prepare site-specifically albumin-conjugated 4D5scFv, which can have versatile clinical applications with improved efficacy.

The Investigation of the Subtle Structural Discrepancies between Oryza Sativa Recombinant and Plasma-Derived Human Serum Albumins to Design a Novel Nanoparticle as a Taxane Delivery System.

To solve the large size faultiness of Oryza sativa recombinant human serum albumin nanoparticle (OsrHSA NP), the structural discrepancies between OsrHSA and plasma-derived human serum albumin (pdHSA) were analyzed deeply in this research. It demonstrated that there were some subtle structural discrepancies located in subdomain IA and IIA between OsrHSA and pdHSA, which included peptide backbone, disulphide bridge and some amino acids. Firstly, the structural discrepancies were investigated through literature comparison, it inferred that the structural discrepancies resulted from the fatty acid (FA) binding to OsrHSA at site 2 of subdomain IA and IIA. To form a cavity for accommodation of FA molecule in OsrHSA, the peptide backbone structure of subdomain IA and IIA would change, accompanied by the conformational transition of disulphide bridges and side chain structure change of some amino acids in subdomain IA and IIA. These alterations induced the exposure of tryptophan (Trp) and tyrosine (Tyr) residues in subdomain IA and IIA and the decrease of net negative charges of molecular surface. The former would promote more OsrHSA molecules aggregate, and the latter would weaken the electrostatic repulsion. As a result, the size of OsrHSA NP was more extensive than that of pdHSA NP (175.84 ± 15.63 nm vs. 31.67 ± 1.31 nm) when the concentration of Dimethyl Sulphoxide (DMSO) was 30% (v/v). In this study, the experimental scheme of OsrHSA NP preparation was improved. There were two changes in the enhanced preparation scheme: pH 8.2 PBS buffer and 63% DMSO. It indicated that the improved OsrHSA NP carrier was comparable to the pdHSA NP carrier. The size and drug loading of paclitaxel-loaded improved OsrHSA NP were 53.57 ± 3.63 nm and 7.25 ± 0.46% (w/w), and those of docetaxel-loaded improved OsrHSA NP were 44.75 ± 2.26 nm and 8.43 ± 0.74% (w/w). Moreover, both NPs exhibited good stability for 168 h at 7.4 pH values. It is established that the improved OsrHSA NP is comparable to the pdHSA NP as a taxane delivery system.

Biodegradable suture development-based albumin composites for tissue engineering applications.

Recent advancements in the field of biomedical engineering have underscored the pivotal role of biodegradable materials in addressing the challenges associated with tissue regeneration therapies. The spectrum of biodegradable materials presently encompasses ceramics, polymers, metals, and composites, each offering distinct advantages for the replacement or repair of compromised human tissues. Despite their utility, these biomaterials are not devoid of limitations, with issues such as suboptimal tissue integration, potential cytotoxicity, and mechanical mismatch (stress shielding) emerging as significant concerns. To mitigate these drawbacks, our research collective has embarked on the development of protein-based composite materials, showcasing enhanced biodegradability and biocompatibility. This study is dedicated to the elaboration and characterization of an innovative suture fabricated from human serum albumin through an extrusion methodology. Employing a suite of analytical techniques-namely tensile testing, scanning electron microscopy (SEM), and thermal gravimetric analysis (TGA)-we endeavored to elucidate the physicochemical attributes of the engineered suture. Additionally, the investigation extends to assessing the influence of integrating biodegradable organic modifiers on the suture's mechanical performance. Preliminary tensile testing has delineated the mechanical profile of the Filament Suture (FS), delineating tensile strengths spanning 1.3 to 9.616 MPa and elongation at break percentages ranging from 11.5 to 146.64%. These findings illuminate the mechanical versatility of the suture, hinting at its applicability across a broad spectrum of medical interventions. Subsequent analyses via SEM and TGA are anticipated to further delineate the suture's morphological features and thermal resilience, thereby enriching our comprehension of its overall performance characteristics. Moreover, the investigation delves into the ramifications of incorporating biodegradable organic constituents on the suture's mechanical integrity. Collectively, the study not only sheds light on the mechanical and thermal dynamics of a novel suture material derived from human serum albumin but also explores the prospective enhancements afforded by the amalgamation of biodegradable organic compounds, thereby broadening the horizon for future biomedical applications.

Contrast Agents Based on Human Serum Albumin and Nitroxides for 1H-MRI and Overhauser-Enhanced MRI.

In cancer diagnostics, magnetic resonance imaging (MRI) uses contrast agents to enhance the distinction between the target tissue and background. Several promising approaches have been developed to increase MRI sensitivity, one of which is Overhauser dynamic nuclear polarization (ODNP)-enhanced MRI (OMRI). In this study, a macromolecular construct based on human serum albumin and nitroxyl radicals (HSA-NIT) was developed using a new synthesis method that significantly increased the modification to 21 nitroxide residues per protein. This was confirmed by electron paramagnetic resonance (EPR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF) mass spectrometry. Gel electrophoresis and circular dichroism showed no significant changes in the structure of HSA-NITs, and no oligomers were formed during modification. The cytotoxicity of HSA-NITs was comparable to that of native albumin. HSA-NITs were evaluated as potential "metal-free" organic radical relaxation-based contrast agents for 1H-MRI and as hyperpolarizing contrast agents for OMRI. Relaxivities (longitudinal and transversal relaxation rates r1 and r2) for HSA-NITs were measured at different magnetic field strengths (1.88, 3, 7, and 14 T). Phantoms were used to demonstrate the potential use of HSA-NIT as a T1- and T2-weighted relaxation-based contrast agent at 3 T and 14 T. The efficacy of 1H Overhauser dynamic nuclear polarization (ODNP) in liquids at an ultralow magnetic field (ULF, B0 = 92 ± 0.8 µT) was investigated for HSA-NIT conjugates. The HSA-NITs themselves did not show ODNP enhancement; however, under the proteolysis conditions simulating cancer tissue, HSA-NIT conjugates were cleaved into lower-molecular-weight (MW) protein fragments that activate ODNP capabilities, resulting in a maximum achievable enhancement |Emax| of 40-50 and a radiofrequency power required to achieve half of Emax, P1/2, of 21-27 W. The HSA-NIT with a higher degree of modification released increased the number of spin probes upon biodegradation, which significantly enhanced the Overhauser effect. Thus, HSA-NITs may represent a new class of MRI relaxation-based contrast agents as well as novel cleavable conjugates for use as hyperpolarizing contrast agents (HCAs) in OMRI.

HSA-nanobinders crafted from bioresponsive prodrugs for combined cancer chemoimmunotherapy-an in vitro exploration.

Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer still lacking effective treatment options. Chemotherapy in combination with immunotherapy can restrict tumor progression and repolarize the tumor microenvironment towards an anti-tumor milieu, improving clinical outcome in TNBC patients. The chemotherapeutic drug paclitaxel has been shown to induce immunogenic cell death (ICD), whereas inhibitors of the indoleamine 2,3- dioxygenase 1 (IDO1) enzyme, whose expression is shared in immune regulatory and tumor cells, have been revealed to enhance the anti-tumor immune response. However, poor bioavailability and pharmacokinetics, off-target effects and hurdles in achieving therapeutic drug concentrations at the target tissue often limit the effectiveness of combination therapies. Methods: This work describes the development of novel biomimetic and carrier-free nanobinders (NBs) loaded with both paclitaxel and the IDO1 inhibitor NLG919 in the form of bioresponsive and biomimetic prodrugs. A fine tuning of the preparation conditions allowed to identify NB@5 as the most suitable nanoformulation in terms of reproducibility, stability and in vitro effectiveness. Results and discussion: Our data show that NB@5 effectively binds to HSA in cell-free experiments, demonstrating its protective role in the controlled release of drugs and suggesting the potential to exploit the protein as the endogenous vehicle for targeted delivery to the tumor site. Our study successfully proves that the drugs encapsulated within the NBs are preferentially released under the altered redox conditions commonly found in the tumor microenvironment, thereby inducing cell death, promoting ICD, and inhibiting IDO1.

Black rice anthocyanins nanoparticles based on bovine serum albumin and hyaluronic acid: Preparation, characterization, absorption and intestinal barrier function protection in Caco-2 monolayers.

Black rice anthocyanins (BRA) nanoparticles (NPs) were prepared using hyaluronic acid (HA), oxidized hyaluronic acid (OHA) and bovine serum albumin (BSA) to enhance the absorption and bioactivity of anthocyanins (ACNs). Results showed that HA/OHA-BSA-BRA NPs had a spherical morphology and excellent dispensability, with hydrated radius ~ 500 nm, zeta potential ~ - 30 mV, and encapsulation efficiency ~21 %. Moreover, using in vitro gastrointestinal release assay, we demonstrated that both BRA-loaded NPs exhibited effective controlled release properties of ACNs, significantly enhancing the accessibility of ACNs to the intestine. Cellular experiments showed that both two NPs had good biocompatibility and increased uptake of BRA. Furthermore, in comparison to the free BRA group, both BRA NPs groups significantly decreased the TEER value and increased the expression of tight junction proteins (Claudin 1, Occludin and ZO-1) in Caco-2 cell monolayers with LPS-induced damage. Therefore, our study demonstrated that HA/OHA-BSA-BRA NPs are promising carriers of ACNs and can effectively prevent the LPS-induced intestinal barrier injury in vitro.

Development of D-π-A organic dyes for discriminating HSA from BSA and study on dye-HSA interaction.

HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M-H-SO3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M-H-SO3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be âˆ¼ 40 nM. Studies on the interaction mechanism revealed that dye M-H-SO3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M-H-SO3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids.

Serum albumin and cardiovascular disease: a Mendelian randomization study.

BACKGROUND: An increasing body of evidence suggests that serum albumin levels play a role in cardiovascular diseases. However, the specific causal relationship between serum albumin levels and cardiovascular disease remains partially unknown. METHODS: Mendelian randomization (MR) was employed in this study to examine potential causal relationships between instrumental variables and cardiovascular diseases. Specifically, we utilized genetic variants of serum albumin levels within the reference range as our instrumental variables. To acquire data on genetic associations with cardiovascular diseases, we sourced information from renowned genome-wide association studies such as UK BioBank, EMBL-EBI, and FinnGen. Notably, our study leveraged summary statistics from large cohorts that have been previously described. RESULTS: We explored the association between serum albumin levels and various conditions, including heart failure (HF), venous thromboembolism (VTE), stroke, atrial fibrillation (AF), coronary artery disease (CAD), type 2 diabetes (T2DM), and pulmonary heart disease (PHD). Genetically predicted serum albumin levels were associated with PHD (odds ratio = 0.737, 95% CI = 0.622 - 0.874, P < 0.001), AF (odds ratio = 0.922, 95% CI = 0.870 - 0.977, P = 0.006), VTE (odds ratio = 0.993, 95% CI = 0.991 - 0.995, P < 0.001), and Stroke (odds ratio = 0.997, 95% CI = 0.995 - 0.999, P = 0.002). However, genetically predicted serum albumin level traits were not associated with HF, CAD and T2DM. CONCLUSION: Our study demonstrates a significant association between serum albumin levels and cardiovascular disease, underscoring the crucial role of low serum albumin as a predictive factor in patients with cardiovascular disease.

Zinc-Substituted Hemoglobin-Albumin Cluster as a Porphyrin-Carrier for Enhanced Photodynamic Therapy.

Apohemoprotein is focused on the field of theranostics, serving as a porphyrin carrier. Hemoglobin (Hb) consists of α2ß2 tetramer with iron(II)-protoporphyrin IX (heme) bound to each globin. However, heme-removed Hb (apoHb) causes dissociation at αß interfaces and aggregation under physiological conditions. We synthesized a stable apoHb derivative comprising intramolecular-crosslinked apoHb (apoXHb) and human serum albumin (HSA), apoXHb-HSA3. ApoXHb-HSA3 engendered no aggregates in the physiological solutions. Moreover, apoXHb-HSA3 was reconstituted with zinc(II)-protoporphyrin IX (ZnP), generating ZnXHb-HSA3, a potent photosensitizer for photodynamic therapy (PDT). The photophysical properties of ZnXHb-HSA3 were identical to those of zinc-substituted XHb (ZnXHb). Cellular uptake behavior was evaluated using various cancer cell lines. ZnXHb-HSA3 released ZnP around the cells, and the free ZnP penetrated cell membranes. In contrast, protein units were not observed within the cells. ZnXHb-HSA3 showed no cytotoxicity under dark conditions and demonstrated superior PDT activity in comparison to naked ZnXHb. ZnXHb-HSA3 acts as an innovative porphyrin carrier for enhanced PDT.

Factors Affecting Psoas Muscle Mass Index in Patients Undergoing Peritoneal Dialysis.

INTRODUCTION: Many patients with chronic kidney disease (CKD), including peritoneal dialysis (PD), have sarcopenia. It is important to evaluate muscle mass to prevent sarcopenia in the field of CKD management. Recently, muscle mass assessment using psoas muscle evaluated by computed tomography (CT) has been reported in patients undergoing hemodialysis. However, few clinical studies have investigated the clinical factors associated with the evaluation of psoas muscle in patients undergoing PD. METHODS: Psoas muscle mass index (PMI) was measured in cross-sectional areas of the bilateral psoas muscles at the third lumbar spine level to evaluate psoas muscle status. The associations between PMI and possible clinical factors were investigated in 68 patients undergoing PD. RESULTS: The mean PMI was 6.3 ± 2.0 cm2/m2, and the PMI was higher in men than in women (p < 0.001). In a multivariable linear regression analysis of the factors associated with PMI, male gender (standardized coefficient: 0.331), body mass index (standardized coefficient: 0.283), serum creatinine concentration (standardized coefficient: 0.289), serum albumin concentration (standardized coefficient: 0.235), and the use of vitamin D (standardized coefficient: 0.195) were independently identified. CONCLUSION: PMI was independently and significantly associated with gender, BMI, serum creatinine concentration, serum albumin concentration and the use of vitamin D. Further prospective studies are needed to clarify whether the maintenance of nutritional status or vitamin D administration could affect muscle mass in patients undergoing PD.

Insights into the binding of buspirone to human serum albumin using multi-spectroscopic and molecular docking techniques.

Buspirone is an anxiolytic drug that plays a significant role in managing anxiety disorders and alleviating their symptoms as well. Several techniques were utilized to study the interaction between buspirone and human serum albumin under physiological conditions, including UV-vis absorption spectroscopy, fluorescence emission spectroscopy, circular dichroism, Fourier transform infrared spectroscopy (FT-IR), equilibrium dialysis, and molecular docking. The results of this study demonstrated that buspirone quenched the intrinsic fluorescence of human serum albumin through a mixed mechanism. Moreover, the binding constants (Kb), the quenching constants (Ksv), and thermodynamic parameters were calculated at various temperatures. The binding process of buspirone to human serum albumin showed a cooperative binding pattern, confirmed by the Scatchard diagram and Hill coefficient. Molecular docking results showed that buspirone interacted with the IIA, IIIA, and IIB subdomains of human serum albumin and slightly changed its conformation. It was also found that hydrophobic forces played a major role in this interaction. This study consequently proves that BSH as a drug can be transported by blood albumin. Additionally, due to its ratiometric response in absorbance upon binding to a biological target, HSA can be used as a molecular probe to follow biomolecular interactions.

Serum albumin levels and risk of atrial fibrillation: a Mendelian randomization study.

Objective: Although several observational studies have linked serum albumin to cardiovascular disease and considered it as an important biomarker, little is known about whether increasing or maintaining serum albumin levels can effectively improve the prognosis of patients with atrial fibrillation. Therefore, this study aims to further explore the causal relationship between serum albumin and atrial fibrillation and its potential mechanism. Method: Using data from large-scale genome-wide association studies, we conducted a two-sample Mendelian randomization (MR) analysis and a mediation MR analysis, using serum albumin as the exposure variable and atrial fibrillation as the outcome variable. We included 486 serum metabolites as potential mediating factors. To increase the robustness of the analysis, we applied five statistical methods, including inverse variance weighted, weighted median, MR-Egger, simple mode, and weighted mode. Validate the MR results using Bayesian weighted Mendelian randomization method. Result: The results of the MR analysis indicate a significant inverse association between genetically predicted serum albumin concentration (g/L) and the risk of atrial fibrillation (Beta = -0.172, OR = 0.842, 95% CI: 0.753-0.941, p = 0.002). Further mediation MR analysis revealed that serum albumin may mediate the causal relationship with atrial fibrillation by affecting two serum metabolites, docosatrienoate and oleate/vaccenate, and the mediating effect was significant. In addition, all our instrumental variables showed no heterogeneity and level-multiplicity in the MR analysis. To verify the stability of the results, we also conducted a sensitivity analysis using the leave-one-out method, and the results further confirmed that our findings were robust and reliable. Finally, we conducted a validation using the Bayesian weighted Mendelian randomization method, which demonstrated the reliability of our causal inference results. Conclusion: This study strongly demonstrates the causal relationship between serum albumin and reduced risk of atrial fibrillation through genetic methods, and reveals the key mediating role of two serum metabolites in this relationship. These findings not only provide a new perspective for our understanding of the role of serum albumin in atrial fibrillation, but also provide new ideas for the prevention and treatment strategies of atrial fibrillation.

Blood Urea Nitrogen to Serum Albumin Ratio as a New Indicator of Disease Severity and Prognosis in Idiopathic Pulmonary Artery Hypertension.

BACKGROUND: Emerging evidence has shown that the blood urea nitrogen to serum albumin ratio (BAR) is associated with the severity and prognosis of heart failure. However, its role in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study investigated the associations between BAR and functional status, echocardiographic findings, hemodynamics, and long-term outcomes among patients with IPAH. METHODS: This study included consecutive patients who underwent right heart catheterization (RHC) and were diagnosed with IPAH between January 2013 and January 2018 at Fuwai Hospital. The primary outcome was the worsening of clinical symptoms. Spearman correlation coefficients were used to evaluate the association between the BAR and established markers of IPAH severity. Receiver operating characteristic (ROC) curve analysis was used to determine BAR's optimal cut-off and predictive performance. Kaplan-Meier analysis and Cox proportional hazard models assessed the relationship between BAR and clinical worsening. RESULTS: A total of 340 patients with IPAH were included in this study. BAR correlated with well-validated variables that reflected the severity of IPAH, such as World Health Organization functional class, 6-min walk distance, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, mixed venous oxygen saturation, and cardiac index. Kaplan-Meier curves indicated that patients with BAR＞3.80 had a significantly higher clinical worsening rate (log-rank test, P < 0.001) than those with BAR≤3.80. Multivariate Cox analysis showed that BAR could independently predict clinical worsening [hazard ratio(HR):1.177, 95% confidence interval (CI):1.014-1.367, P=0.005]. In addition, BAR provided additional predictive value for the European Society of Cardiology (ESC)/European Respiratory Society (ERS) risk assessment score. CONCLUSIONS: BAR reflects disease severity and is independently associated with the prognosis of patients with IPAH.

Hierarchical mesoporous silicon and albumin composite microparticles delivering DOX and FU for liver cancer treatment.

Drug delivery systems based on hydrogel microcarriers have shown enormous achievements in tumor treatment. Current research direction mainly concentrated on the improvement of the structure and function of the microcarriers to effectively deliver drugs for enhanced cancer treatment with decreased general toxicity. Herein, we put forward novel hierarchical mesoporous silicon nanoparticles (MSNs) and bovine serum albumin (BSA) composite microparticles (MPMSNs@DOX/FU) delivering doxorubicin (DOX) and 5-fluorouracil (FU) for effective tumor therapy with good safety. The DOX and FU could be efficiently loaded in the MSNs, which were further encapsulated into methacrylate BSA (BSAMA) microparticles by applying a microfluidic technique. When transported to the tumor area, DOX and FU will be persistently released from the MPMSNs@DOX/FU and kept locally to lessen general toxicity. Based on these advantages, MPMSNs@DOX/FU could observably kill liver cancer cells in vitro, and evidently suppress the tumor development of liver cancer nude mice model in vivo. These results suggest that such hierarchical hydrogel microparticles are perfect candidates for liver cancer treatment, holding promising expectations for impactful cancer therapy.