Generating globin-like reactivities in [human serum albumin-FeII(heme)] complex through N-donor ligand addition.

Human serum albumin (HSA) has a strong binding affinity for heme b, forming a complex in a 1:1 ratio with the co-factor ([HSA-FeIIIheme]). This system displays spectroscopic and functional properties comparable to globins when chemical derivatives mimicking them are incorporated into the protein matrix. The aim of this study is to generate globin-like systems using [HSA-FeIIIheme] as a protein template and binding N-donor ligands (imidazole, Im; and 1-methylimidazole, 1-MeIm) to construct artificial [HSA-Fe(heme)-(N-donor)] complexes. Their electronic structure and binding thermodynamics are investigated using UV-vis and (synchronous) fluorescence spectroscopies, while ligand-protein interactions are visualized using docking simulations. The imidazole derivatives have a strong affinity for [HSA-FeIIIheme] (K âˆ¼ 104-106), where the spontaneous binding of Im and 1-MeIm are dominated by entropic and enthalpic effects, respectively. The reduced form of the [HSA-Fe(heme)-(N-donor)] complexes demonstrate nitrite reductase (NiR) activity similar to that observed in globins, but with significant differences in their rates. [HSA-FeIIheme-(1-MeIm)] reduces nitrite ∼4× faster than the Im analogue, and âˆ¼ 30× faster than myoglobin (Mb). The enhanced NiR activity of [HSA-FeIIheme-(1-MeIm)] is a cumulative effect of several factors including a slightly expanded and more optimal heme binding pocket, nearby residues as possible proton sources, and a H-bonding interaction between 1-MeIm and residues Arg160 and Lys181 that may have a long-distance influence on the heme π electron density.

89Zr-Labeled DFO@Durvalumab-HSA nanoparticles: In vitro potential for triple-negative breast cancer.

This study presents the development and evaluation of a DFO@mAb-NP (DFO@Durvalumab-HSA-DTX nanoparticle) nanoplatform for imaging in triple-negative breast cancer (TNBC). The nanoplatform demonstrated significant changes postconjugation with DFO, evidenced by increased particle size from 178.1 ± 5 nm to 311 ± 26 nm and zeta potential alteration from -31.9 ± 3 mV to -40.5 ± 0.8 mV. Fourier-transform infrared spectroscopy and ultraviolet spectral analyses confirmed successful DFO conjugation, with notable shifts in peak wavelengths. High labeling efficiency was achieved with 89Zr, as indicated by thin layer radio chromatography and high-performance liquid radio chromatography results, with labeling efficiencies of 98 ± 2% for 89Zr-DFO@mAb and 96 ± 3% for 89Zr-DFO@mAb-NP. The nanoplatforms maintained stability over 24 h, showing less than 5% degradation. Lipophilicity assays revealed logP values of 0.5 ± 0.03 for 89Zr-DFO@mAb-NP and 0.98 ± 0.2 for 89Zr-DFO@mAb, indicating a higher lipophilic tendency in the radiolabeled Durvalumab. Cell uptake experiments showed an initial high uptake in MDA-MB-468 cells (45.1 ± 3.2%), which decreased over time, highlighting receptor-specific interactions. These comprehensive findings suggest the promising potential of the DFO@mAb-NP nanoplatform for targeted imaging in TNBC, with implications for improved diagnostic accuracy and treatment strategies.

Formation of bovine serum albumin-galangin nanoparticles and their potential to inhibit ROS-induced inflammation: Enthanol desolvation vs. pH-shiftng method.

pH-shifting method, as an eco-friendly approach, is a promising alternative to desolvation method, yet systematic comparison of their property is still lacking. In this study, bovine serum albumin-galangin nanoparticles (BSA-GA NPs) were designed for alleviating ROS-mediated macrophage inflammation by the 2 separate methods. Compared with the desolvation method, BSA exhibited a higher loading capacity for GA under the pH-shifting method, which was attributed to the exposure of the binding site leading to enhanced affinity for GA and a more compact particle structure. Further analyses evidenced that the electron arrangement and crystal structure of GA changed with different methods. The content of random coil of BSA was elevated after pH-shifting method. Besides, the smaller size rendered the pH-shifting treated BSA-GA NPs easier to be taken up by macrophages, while the enhanced specific surface area conferred excellent ROS scavenging and anti-inflammatory performances. This study may provide new insights into the choice of loading methods.

Utility of Quantitative Assessment of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl Human Serum Albumin SPECT/CT in the Identification of Severe Liver Fibrosis: Its Complementary Diagnostic Value with Other Liver Function Indices.

PURPOSE: To evaluate the value of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (99mTc-GSA) single photon emission computed tomography (SPECT) for assessing liver fibrosis, and to assess its complementary value to other liver function indices such as fibrosis-4 (FIB-4) index and indocyanine green (ICG) clearance test parameters (ICG-R15 and ICG-K). PROCEDURES: Seventy-eight patients with chronic liver disease and hepatocellular carcinoma who underwent 99mTc-GSA scintigraphy and other liver function tests including ICG test and FIB-4 index prior to hepatectomy were studied. 99mTc-GSA imaging was performed with SPECT/CT scanner (Discovery NM/CT 670). Immediately after injection of 99mTc-GSA, dynamic imaging was performed for 20 min, followed by SPECT data acquisition for 6 min. LHL15 which is a conventional index by 99mTc-GSA planar images, and liver uptake ration (LUR) was measured from 99mTc-GSA SPECT images. From the liver resection specimens, the degree of liver fibrosis was graded according to the Ludwig scale (F0-4). RESULTS: Significant differences in LUR, LHL15, ICG-R15, ICG-K, platelet count and FIB-4 index were found between the F0-3 and F4 liver fibrosis patient groups (P < 0.05). Multivariate logistic regression analysis revealed that LUR and ICG-K were independent factors for identifying severe liver fibrosis (F4). Area under the curve of receiver operating curve analysis for the logistic regression model using LUR and ICG-K was 0.83. In the patient group with higher FIB-4 (≥ 3.16), the diagnostic performance of LUR for detecting severe liver fibrosis was significantly better than LHL15 (AUC: 0.83 vs. 0.75, P = 0.048). In the high FIB-4 index group, the sensitivity and specificity for identifying F4 was 88% and 85%, respectively, with LUR cutoff value of 41.2%. CONCLUSIONS: LUR, measured by 99mTc-GSA SPECT, is a useful indicator for identifying sever liver fibrosis. Particularly in patients with high FIB-4 index (≥ 3.16), LUR can be a valuable indicator to identify severe liver fibrosis with high diagnostic accuracy.

Aggregation behavior, interaction forces and physico-chemical parameters of cetyltrimethylammonium chloride in aqueous solution of bovine serum albumin: Impacts of short-chain alcohols and temperature.

To better understand the molecular interactions between cetyltrimethylammonium chloride (CTAC) and bovine serum albumin (BSA), we report the alteration of the physicochemical characteristics of CTAC in aqueous BSA solutions in the presence of different alcohols. The analyses were performed using the conductivity method at temperatures ranging from 298.15 to 323.15 K, with 5 K intervals. The critical micelle concentration (CMC) values of the BSA + CTAC systems were found to change with variations in alcohol type, solvent composition, and temperature. The CMC values grew with the rising alcohol content. The negative free energy changes (∆Gm0) indicated the spontaneous association of the systems in all solvents media. The magnitudes of ∆Hm0 and ∆Sm0, determined from the micellization of the systems, indicated the presence of electrostatic, ion-dipole, and hydrophobic forces. The thermodynamics of transfer (free energy ((∆Gm,tr0), enthalpy (∆Hm,tr0), entropy (∆Sm,tr0)), and compensation parameters (∆Hm0,∗ and Tc)-were also calculated, providing significant insights into the potential interactions between CTAC and BSA in the presence of various alcohol additives. Furthermore, molecular docking studies suggested the binding of CTAC to different BSA binding sites with varying affinities.

[Volume therapy: which preparation for which situation?] / Volumentherapie ­ welches Präparat in welcher Situation?

The most commonly used fluids for volume therapy are crystalloids and colloids. Crystalloids comprise 0.9% sodium chloride and balanced crystalloids (BC). Colloids can be divided into artificial colloids and human albumin (a natural colloid). Large studies show advantages for BC over 0.9% NaCl with respect to renal endpoints, probably due to the unphysiologically high chloride content of 0.9% NaCl. However, other studies, such as the BaSICS and PLUS trials, showed no significant differences in mortality in a heterogeneous population. Despite this, meta-analyses suggest advantages for BC. Therefore, BC should be preferred, especially in patients at increased risk of acute kidney injury, with acidemia and/or hyperchloremia. Except for specific indications (e.g., in patients with cirrhosis, sepsis resuscitation after initial volume therapy with BC), albumin should not be used. There is clear evidence of harm from hydroxyethyl starch in intensive care patients.

Tissue-Adaptive BSA Hydrogel with Dual Release of PTX and bFGF Promotes Spinal Cord Injury Repair via Glial Scar Inhibition and Axon Regeneration.

Spinal cord injury (SCI) is a severe clinical disease usually accompanied by activated glial scar, neuronal axon rupture, and disabled motor function. To mimic the microenvironment of the SCI injury site, a hydrogel system with a comparable mechanical property to the spinal cord is desirable. Therefore, a novel elastic bovine serum albumin (BSA) hydrogel is fabricated with excellent adhesive, injectable, and biocompatible properties. The hydrogel is used to deliver paclitaxel (PTX) together with basic fibroblast growth factor (bFGF) to inhibit glial scar formation as well as promote axon regeneration and motor function for SCI repair. Due to the specific interaction of BSA with both drugs, bFGF, and PTX can be controllably released from the hydrogel system to achieve an effective concentration at the wound site during the SCI regeneration process. Moreover, benefiting from the combination of PTX and bFGF, this bFGF/PTX@BSA system significantly aided axon repair by promoting the elongation of axons across the glial scar with reduced reactive astrocyte secretion. In addition, remarkable anti-apoptosis of nerve cells is evident with the bFGF/PTX@BSA system. Subsequently, this multi-functionalized drug system significantly improved the motor function of the rats after SCI. These results reveal that bFGF/PTX@BSA is an ideal functionalized material for nerve repair in SCI.

Does serum albumin at the onset of necrotising enterocolitis predict severe disease in preterm infants?

OBJECTIVE: To investigate whether laboratory markers obtained at the onset of necrotising enterocolitis (NEC) predict the severity of the disease in preterm infants. METHODS: Prospective cohort study conducted in a tertiary referance hospital. A total of 88 preterm infants were included in the study. Of those, 60 infants had the diagnosis of severe NEC, while the remaining 28 infants constituted the non-severe NEC group. Severe NEC was defined as surgical NEC or NEC-related mortality. Infants with and without severe NEC were compared in terms of demographic, clinical and laboratory characteristics. RESULTS: At the onset of disease, infants with severe NEC noted to have lower platelet count and serum ALB levels (p = 0.011, p = 0.004; respectively), whereas higher CRP, and serum lactate levels (p = 0.009, p = 0.008; respectively). Multiple binary logistic regression analyses showed that CRP (1.03(1.01-1.05), p = 0.024) and serum albumin level (0.16(0.04-0.64), p = 0.010) were statistically significant independent risk factors for severe NEC. The optimal cut-off value for the serum ALB level was found to be 23 g/L with 52% sensitivity (95%CI: 37-68%) and 84% specificity (95%CI: 60-97%) (AUC 0.727; p = 0.002). CONCLUSION: Serum ALB level at NEC onset might be a reliable biomarker for severe disease in preterm infants.

Binding characteristics of the major kratom alkaloid, mitragynine, towards serum albumin: spectroscopic, calorimetric, microscopic, and computational investigations.

Mitragynine (MTG) is a prominent indole alkaloid that is present abundantly in Mitragyna speciosa, commonly referred to as kratom. MTG has garnered significant attention due to its selective agonistic characteristics towards opioid receptors and related analgesic effects. In the circulatory system, the in vivo efficacy of MTG is dictated by its interaction with plasma proteins, primarily human serum albumin (HSA). In the present study, we utilized a broad methodology that included spectroscopic, calorimetric, microscopic, and in silico approaches to characterize the interaction between MTG and HSA. Alterations in the UV absorption spectrum of HSA by the presence of MTG demonstrated a ground-state complexation between the protein and the ligand. The Ka values obtained for the MTG-HSA interaction were in the range 103-104 M-1 based on analysis of fluorescence and ITC data, respectively, indicating an intermediate binding affinity. The binding reaction was thermodynamically favorable as revealed by ΔH, ΔS, and ΔG values of -16.42 kJ mol-1, 39.97 J mol-1 K-1, and -28.34 kJ mol-1, respectively. Furthermore, CD spectroscopy results suggested MTG binding induced minimal effects on the structural integrity of HSA, supported by computational methods. Changes in the dimensions of HSA particles due to aggregation, as observed using atomic force microscopy in the presence of MTG. Competitive drug displacement results seemingly suggested site III of HSA located at subdomain IB as the preferred binding site of MTG, but were in inconclusive. However, docking results showed the clear preference of MTG to bind to site III, facilitated by hydrophobic (alkyl and pi-alkyl) and van der Waals forces, together with carbon hydrogen bonds. Additionally, the MTG-HSA complexation was demonstrated to be stable based on molecular dynamics analysis. The outcomes of this study shed light on the therapeutic potential of MTG and can help in the design of more effective derivatives of the compound.

Generation of affinity maps for thiazolidinediones with human serum albumin using affinity microcolumns. II. Effects of advanced glycation end products on multisite drug binding.

Multisite protein interactions by the thiazolidinedione-class drugs pioglitazone and rosiglitazone were examined by using high-performance affinity microcolumns that contained normal human serum albumin (HSA) vs HSA that had been modified to form advanced glycation end products by glyoxal (Go) or methylglyoxal (MGo). The results were used to generate an affinity map for these drugs at several key regions on HSA. Strong binding (∼105 M-1) by these drugs was seen at both Sudlow sites I and II. About a 50 % decrease in the affinities at Sudlow site II was observed for pioglitazone for Go-modified HSA, while either a 47 % decrease or 1.6-fold increase in affinity was seen for MGo-modified HSA, depending on the extent of modification. The binding affinity for rosiglitazone at Sudlow site II had a 40-83 % decrease for Go-modified HSA and either a non-significant change or 1.4-fold increase for MGo-modified HSA. At Sudlow site I, pioglitazone gave a 41 % decrease in affinity for either Go or MGo-modified HSA, and for rosiglitazone up to a 55 % decrease or 1.3-fold increase in affinity was noted. Positive allosteric effects were seen by these drugs with the tamoxifen site of HSA, and neither drug had any notable binding at the digitoxin site for the normal or modified forms of HSA. Rosiglitazone also had weak interactions at a site in subdomain IB, which increased in affinity by up to 5.0-fold with the Go- or MGo-modified HSA. This study illustrated how affinity microcolumns can be used to provide a detailed analysis of solute-protein systems that involve complex interactions. The data obtained should also be valuable in providing a better understanding of how drug interactions with HSA and other proteins can be altered by modifications of these binding agents in diseases such as diabetes.

Relationship between serum albumin level and hospitalization duration following percutaneous coronary intervention for acute coronary syndrome.

Low serum albumin levels increase coronary morbidity, mortality, and postoperative cardiovascular risk. Therefore, this study investigated the relationship between these levels and the length of hospital stay in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome. A total of 350 patients were divided into quartiles according to serum albumin levels. Univariate and multivariate analyses were performed to identify factors associated with the length of hospital stay. A non-linear regression analysis of serum albumin and length of hospital stay was also performed. The results of the multifactorial analysis revealed low serum albumin levels as an independent predictor of longer hospital stay, even in the fully adjusted model. In the segmented linear regression model, serum albumin level showed a U-shaped relationship with the length of hospital stay. In conclusion, low serum albumin level was an independent predictor of longer hospital stay in patients undergoing PCI for acute coronary syndrome, with shorter stays observed for increasing serum albumin levels. Low serum albumin can be used to identify patients who require longer hospitalization and may need additional nutritional support or interventions to improve their prognosis.

Serum albumin, genetic susceptibility, and risk of venous thromboembolism.

Background: Previous research on the association between serum albumin (ALB) and venous thromboembolism (VTE) has produced inconclusive results. The polygenic risk score is constructed from a set of independent risk variants associated with a disorder, enabling the identification of a larger fraction of the population at comparable or greater disease risk. It is still unknown whether ALB and genetic factors jointly contribute to the incidence of VTE. Objectives: The present study aimed to explore ALB, genetic susceptibility, and the risk of VTE. Methods: The present investigation was an analysis of prospectively collected data from UK Biobank, a population-based, longitudinal cohort. Cox proportional models were used to calculate hazard ratios and 95% CIs for VTE. The Kaplan-Meier curve was utilized to visualize the cumulative risk of VTE according to different serum ALB levels, and the restricted cubic spline model was leveraged to explore the exposure-response relationship among ALB levels and VTE risk. Results: During median follow-up of 13.5 years, 11,502 cases with VTE were diagnosed among 417,113 participants in the UK Biobank. The lower ALB levels were associated with a higher risk for VTE. Individuals with both a high genetic risk and lowest ALB level had the highest risk of VTE (hazard ratio, 3.89; 95% CI, 3.41-4.43), compared with those with low genetic risk and highest ALB level. The positive joint effects of low ALB and polygenic risk score increased the risk of VTE in individuals with high genetic risk. This study excluded non-European patients and primarily focused on the European population, which may limit the generalizability of the findings. Conclusion: Low serum ALB levels were linked to an increased risk of VTE, which was in accordance with a linear dose-response relationship. There was a positive additive effect of ALB and genetic susceptibility on the risk of VTE. ALB could serve as a biomarker for predicting the risk of VTE.

Association mechanism of bicalutamide and human serum albumin for potential clinical implications.

The binding mechanism of molecular interaction between bicalutamide and human serum albumin (HSA) in a pH 7.4 phosphate buffer was studied using various spectroscopic techniques in combination with molecular modeling. Fluorescence data revealed that the fluorescence quenching of HSA by bicalutamide was a static quenching procedure. The binding constants and number of binding sites were evaluated at different temperatures. The thermodynamic parameters, ΔH and ΔS, were calculated to be 4.30 × 104 J·mol-1 and 245 J·mol-1·K-1, respectively, suggesting that the binding of bicalutamide to HSA was driven mainly by hydrophobic interactions and hydrogen bonds. The displacement studies indicated neither Sudlow's site I nor II but subdomain IB as the main binding site for bicalutamide on HSA. The binding distance between bicalutamide and HSA was determined to be 3.54 nm based on the Förster theory. Analysis of circular dichroism, synchronous, and 3D fluorescence spectra demonstrated that HSA conformation was slightly altered in the presence of bicalutamide.

The use of concomitant medications on nephrotoxicity associated with teicoplanin: A retrospective observational study.

BACKGROUND: Teicoplanin (TEIC) is a nephrotoxic agent. However, little is known about the effects of concomitant medications on nephrotoxicity. In this study, we investigated the effects of concomitant drugs on nephrotoxicity. METHODS: A retrospective observational case-control study was conducted on patients (≥18 years) who started TEIC at the Tokyo Dental College, Ichikawa General Hospital, between January 2013 and April 2023. The primary outcome was nephrotoxicity, defined as an increase in serum creatinine levels of ≥50 % or ≥0.5 mg/dL from baseline. Logistic regression analysis was used to determine the risk factors for nephrotoxicity associated with TEIC. In addition, we investigated the relationship between nephrotoxicity and predicted free TEIC concentrations. RESULTS: Of 305 patients, 43 (14.1 %) developed nephrotoxicity. The multivariate logistic regression analysis identified that serum albumin (odds ratio [OR] = 0.50, 95 % confidence interval [CI] 0.27-0.89, p = 0.02), concomitant use of loop diuretics (OR = 2.22, 95 % CI 1.10-4.59, p = 0.03), antivirals (OR = 3.24, 95 % CI 1.32-7.62, p < 0.01), and vasopressors (OR = 2.57, 95 % CI 1.10-5.78, p = 0.03) were the associated risk factors for nephrotoxicity in patients administered with TEIC. In 216 patients, predicted TEIC concentrations were 3.6 [interquartile range (IQR), 2.6-4.9] µg/mL in the nephrotoxicity group versus 3.6 [IQR, 2.5-4.7] µg/mL in the non-nephrotoxicity group, with no significant difference (p = 0.69). CONCLUSION: Our results indicate the importance of modifying the concomitant use of loop diuretics, antivirals, and vasopressors.

Ibuprofen­derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non­caspase 3/7­mediated pathway.

Nitric oxide (NO) has been reported to have a cytotoxic effect on various types of cancer. However, the efficient delivery of NO donors to tumors remains challenging. The present study used ibuprofen, which has a high binding affinity to human serum albumin (HSA). A total of two types of nitrated forms of ibuprofen, 4-[(nitrooxy)methyl]benzyl 2-(4-isobutylphenyl)propanoate [nitrated ibuprofen benzyl linker (NIB)] and 2-(nitrooxy)ethyl 2-(4-isobutylphenyl) propanoate [nitrated ibuprofen ethyl linker (NIE)], were synthesized. It was demonstrated that both NIB and NIE bound to the ibuprofen-binding site of HSA. Although NOx release was observed from NIB, but not NIE, intracellular NO release was detected from both NIB and NIE, which indicated that the mechanisms of NO release may be different for NIB and NIE. Both NIB and NIE induced concentration- and time-dependent cell death in human pancreatic cancer cells, whereas this cell death was not observed with ibuprofen, which could suggest that these cell death-inducing effects may be mediated by NO. The non-specific caspase inhibitor, z-VAD-FMK, inhibited cell death induced by NIB and NIE, but activation of caspase 3/7 was not observed. These results suggested that both NIB and NIE induced cell death through a non-caspase 3/7 pathway. The findings of the present study demonstrated that both NIB and NIE, as NO donors that could be retained in blood, may potentially be useful anti-cancer agent candidates in the future.

Interactions of human serum albumin with phosphate and Tris buffers: impact on paclitaxel binding and nanoparticles self-assembly.

AIM: To investigate the conformational changes in human serum albumin (HSA) caused by chemical (CD) and thermal denaturation (TD) at pH 7.4 and 9.9, crucial for designing controlled drug delivery systems with paclitaxel (PTX). METHODS: Experimental and computational methods, including differential scanning calorimetry (DSC), UV-Vis and intrinsic fluorescence spectroscopy, mean diameter, polydispersity index (PDI), ζ-potential, encapsulation efficiency (EE), in vitro release and protein docking studies were conducted to study the HSA denaturation and nanoparticles (NPs) preparation. RESULTS: TD at pH 7.4 produced smaller NPs (287.1 ± 12.9 nm) than CD at pH 7.4 with NPs (584.2 ± 47.7 nm). TD at pH 9.9 exhibited high EE (97.3 ± 0.2%w/w) with rapid PTX release (50% within 1h), whereas at pH 7.4 (96.4 ± 2.1%w/w), release only 40%. ζ-potentials were around -30 mV. CONCLUSION: Buffer type and pH significantly influence NP properties. TD in PBS at pH 7.4, provided optimal conditions for a stable and efficient drug delivery system.

Lower Serum Albumin Level: A Prospective Risk Predictor of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in China, at high annual incidence and mortality. Chronic hepatitis B virus infection (CHB) is considered as a leading cause to bring about HCC in China. Serum albumin (ALB) level has been adopted to verify its risk with HCC development as a combination variable with other factors. However, the predictive value of a single ALB level on HBV-related HCC risk remained unclear. The aim of this study was to evaluate the prediction ability of serum ALB concentration on the risk of HBV-related HCC development. A prospectively enrolled clinical cohort compromising 2932 cases of CHB patients with at least 1-year exclusion window was selected to explore the predictive role of serum ALB level on incident HCC risk. Baseline clinical data including host characters and laboratory test were collected at the initial period of hospitalisation. The hazard ratio of ALB level associated with HCC development was assessed by Cox proportional hazards regression model using univariate and multivariate analyses. We evaluated the discrimination accuracy of ALB level in predicting HCC development by receiver operating characteristic (ROC) curves. Dose-dependent and time-dependent effects of ALB level on HCC risk prediction were demonstrated, respectively, using a restricted cubic spline and a Fine and Grey competing risk model. Referred to patients with higher ALB level, those with lower ALB level exhibited significantly increased risk of HCC development after adjustment for host variables (dichotomised analyses: hazard ratio = 3.12, 95% confidence interval 1.63-5.97, p = 8.23 × 10-4, plog-rank = 5.97 × 10-4; tertile analyses: hazard ratio = 2.07, 95% confidence interval 1.63-2.64, p = 3.77 × 10-9, plog-rank < 2.00 × 10-16; quartile analyses: hazard ratio = 2.10, 95% confidence interval 1.56-2.84, p = 9.87 × 10-7, plog-rank < 2.00 × 10-16). There was a statistically increasing trend on HCC risk which was found following by the decrease of ALB level (ptrend < 0.0001). Similar findings were present by the Kaplan-Meier analysis, cumulative incidences of HCC development were significantly higher in patients with lower ALB levels, with the p value obtained from log-rank test were all < 0.0001. The result of dose-dependent effect showed hazard ratio (HR) value of HCC risk was gradually decreasing as the increasing of ALB level, with non-linear correlation being statistically significant (Wald χ2 = 20.59, p = 0.000). HR value in lower ALB level remained persistently prominent by fluctuating around 2.73 in the whole follow-up time by adjusting for host variables. Sub-cohort analysis by ROC revealed that the discrimination ability of the ALB model was performed better than Child-Pugh (C-P) model in both cohort of patients with 1-year (area under curve [AUC] 0.762 vs. 0.720) and 2-year exclusion window (AUC 0.768 vs. 0.728). The AUC added by ALB level was demonstrated significantly from host model to full model. Lower ALB level was significantly associated with an increased risk of HBV-related HCC and could provide extra useful clinical utility to other host features, which might be a promising non-invasive indicator for surveillance on HCC development.

Separation of recombinant erythropoietin and human serum albumin without the use of sophisticated equipment.

A number of drugs based on recombinant erythropoietin contain human serum albumin as an auxiliary component. The presence of this protein hinders the proper control of the drug quality in accordance with the requirements of regulating agencies. We propose the novel method for separation of recombinant erythropoietin (epoetin beta) and human serum albumin. It is based on the subsequent use of hydrophobic sorbent and anion exchange resin placed in gravity flow columns (without the use of spin-columns). The proposed approach makes it possible to concentrate and purify the preparations containing the epoetin beta both at high and at minimal concentrations (the ratio of the amount of albumin and erythropoietin in the used preparations can reach 125:1). The average yield of epoetin beta after the use of hydrophobic sorbent and anion exchange resin was 75% and 97%, respectively. It was shown that the determined conditions of sample preparation had no affect on the content of the epoetin beta in the product.

Nanoparticles of nucleotide-free analogue of vitamin B12 formed in protein nanocarriers and their neuroprotective activity in vivo.

Recently, we have described the first supermolecular nanoentities of vitamin B12 derivative, viz. monocyano form of heptabutyl cobyrinate, unique nanoparticles with strong noncovalent intermolecular interactions, emerging optical and catalytic properties. Their nearest analogue, heptamethyl cobyrinate (ACCby), exhibits bioactivity. Here, we demonstrate the first example of the formation of nanoparticles of this nucleotide-free analogue of vitamin B12 in protein nanocarriers and neuroprotective activity in vivo of the own nanoform of the drug. The preparation and characterization of nanocarriers based on bovine serum albumin (BSA) loaded with vitamin B12 (viz. cyano- and aquacobalamins) and ACCby were performed. Nucleotide-free analogue of vitamin B12 is tightly retained by the protein structure and exists in an incorporated state in the form of nanoparticles. The effect of encapsulated drugs on the character and severity of primary generalized seizures in rats induced by the pharmacotoxicant thiosemicarbazide was studied. Cyanocobalamin and ACCby exhibited a neuroprotective effect. The best influence of the encapsulation on the effectiveness of the drugs was achieved in the case of AСCby, whose bioavailability as a neuroprotector did not change upon introduction in BSA particles, i.e., 33 % of surviving animals were observed upon ACCby administration in free form and in encapsulated state. No surviving rats were observed without the administration of drugs. Thus, BSA nanocarriers loaded by nanoparticles of nucleotide-free analogues of vitamin B12, including hydrophobic ones, can be recommended for neuroprotection and targeted delivery.

Preoperative low serum albumin increases the rate of perioperative blood transfusion in patients undergoing total joint arthroplasty: propensity score matching.

BACKGROUND: To investigate the relationship between preoperative low serum albumin and perioperative blood transfusion in patients undergoing total joint arthroplasty (TJA). METHODS: We enrolled 2,772 TJA patients from our hospital between January 1, 2017, and January 1, 2022. Clinical data were extracted from electronic medical records, including patient ID, sex, BMI (Body Mass Index), age, and diagnoses. Receiver operating characteristic curves were constructed to establish thresholds for serum albumin levels categorization. Propensity score matching (PSM) was developed with preoperative serum albumin as the dependent variable and perioperative blood transfusion-related factors as covariates, including BMI grade, age grade, sex, diagnosis, hypertension, diabetes, coronary heart disease, chronic obstructive pulmonary disease, chronic bronchitis, cerebral infarction, major surgeries within the last 12 months, renal failure, cancer, depression, corticosteroid use, smoking, drinking, and blood type. The low serum albumin group was matched with the normal albumin group at a 1:2 ratio, employing a caliper value of 0.2. Binary logistic regression was employed to analyze the outcomes. RESULTS: An under the curve of 0.601 was discovered, indicating a cutoff value of 37.3 g/L. Following PSM, 892 cases were successfully paired in the low serum (< 37.3 g/L) albumin group, and 1,401 cases were matched in the normal serum albumin (≥ 37.3 g/L) group. Binary logistic regression in TJA patients showed that the albumin OR was 0.911 with 95%CI 0.888-0.935, P < 0.001. Relative to the preoperative normal serum albumin group, TJA patients in the low serum albumin group experienced a 1.83-fold increase in perioperative blood transfusion rates (95% CI 1.50-2.23, P < 0.001). Compared to the normal serum albumin group, perioperative blood transfusion rates for TJA patients with serum albumin levels of 30-37.3 g/L, 25-30 g/L, and ≤ 25 g/L increased by 1.63 (95% CI 1.37-1.99, P < 0.001), 5.4 (95% CI 3.08-9.50, P < 0.001), and 6.43 times (95% CI 1.80-22.96, P = 0.004), respectively. CONCLUSION: In TJA patients, preoperative low serum albumin levels have been found to be associated with an increased risk of perioperative blood transfusion. Furthermore, it has been observed that the lower the preoperative serum albumin level is, the higher the risk of perioperative blood transfusion. TRIAL REGISTRATION: 28/12/2021, Chinese Clinical Trial Registry, ChiCRT2100054844.